pmid
int64 21
9.18M
| title
stringlengths 4
512
| abstract
stringlengths 2
9.99k
|
|---|---|---|
63,574
|
Improved chemotherapy in disseminated testicular cancer.
|
Two combination chemotherapy regimens for disseminated testicular cancer are described. Our present regimen of platinum vinblastine and bleomycin has been highly successful, producing 16 complete (80 per cent) and 4 partial (20 per cent) remissions. Furthermore, 2 patients have been rendered free of disease by the surgical removal of residual disease, making the effective complete remission rate in these 20 patients 90 per cent. Of these patients 16 are alive and 14 are free of disease for more than 8 to more than 20 months. Despite the significant toxicity during the first 12 weeks of this therapeutic regimen it usually was manageable and maintenance therapy produced minimal toxicity. We believe that this regimen is a major advance in the management of patients with disseminated testicular cancer.
|
63,570
|
[Abnormality of the pyelo-ureteric junction revealed by a prostatic adenoma (author's transl)].
|
An acquired hydronephrosis proximal to obstruction caused by a proastatic adenoma regressed after surgical removal of the latter. On this basis, the authors review the lesions predisposing to abnormalities of the junction and the circumstances which may provoke a hydronephrosis.
|
63,575
|
Prostatism and prostatectomy: the value of urine flow rate measurement in the preoperative assessment for operation.
|
Urine flow rates were measured before and after elective prostatic operations in 53 patients. The over-all success rate was 72 per cent, as assessed by the changes in symptoms and urine flow rates. Patients with less than a satisfactory operative result had more frequency and urgency and higher preoperative urine flow rates than patients with good results from the operation. Since bladder conditions unassociated with bladder outflow obstruction may be responsible for the poor results it is recommended that urine flow rates be measured before an elective prostatic operation so that patients unlikely to benefit from an operation may be identified.
|
63,569
|
[Study of the interdependence between prostatic hypertrophy and disorders in hormone levels. Preliminary report. 1. Study of blood testosterone].
|
Using the radioimmunological method and applying the double antibody separation technique, testosterone was determined in 14 patients and LH in a few. A group of men in good health aged between 20 and 60 years (22 persons) was used as a control and a group of men aged from 60 to 90 years (24 persons) in whom the size of the prostate gland corresponded to their age. In 4 patients, testosterone levels were determined before and after prostatectomy. It was found that testosterone levels in the serum of men aged over 60, in good health, were markedly lower. Patients with prostatic hypertrophy showed testosterone concentrations several times higher than the men in the control groups. Testosterone levels in patients with considerable hypertrophy of the prostate were higher than in patients with moderate hypertrophy. Adenomectomy had a remarkable influence on the decrease of testosterone in the serum.
|
63,576
|
Radical prostatectomy: palliation for stage C carcinoma of the prostate.
|
An objective comparison is made of patients with stage C carcinoma of the prostate treated with radical prostatectomy versus more conservative measures. Morbidity from local manifestations of the tumor left in situ was markedly increased, whereas those patients afforded an extirpative operation had a much improved quality of life.
|
63,582
|
Self-instructional emergency medicine program for medical students.
|
A self-instructional program in emergency medicine has been developed for freshmen medical students at the University of Virginia School of Medicine. The cognitive objective of the course is to give the student the minimum level of knowledge to diagnose emergency medical conditions. Performance of the appropriate practical treatment is the course's psychomotor objective. Evaluation of the student's grasp of the program's cognitive and psychomotor objectives is accomplished by the written and practical examination for certification of emergency medical technicians and practical tests in basic life-support. Self-instructional guides, algorithms, videotapes and reading materials are the educational resources for the course. As a result of successful completion of the training program, the student is certified as an emergency medical technician in the Commonwealth of Virginia.
|
63,647
|
Pathogenesis of polycation-induced alterations ("fusion") of glomerular epithelium.
|
Perfusion of rat kidneys with polycations (protamine sulfate, poly-L-lysine), resulted in glomerular epithelial alterations very similar to those observed in proteinuric states, particularly rat aminonucleoside nephrosis. Such changes did not occur after exposure to neutral or anionic macromolecules (poly-DL-alanine, myoglobin, heparin, poly-L-glutamic acid and ovalbumin). Morphigenetic factors in the polycation-induced lesion included retraction and flattening of foot processes, narrowing of filtration slits, formation of occluding junctions between foot processes and cell swelling. The associated suppression of histochemically demonstrable glomerular polyanion suggested that neutralization of cell surface anionic sites was an important factor in the causation of the lesion, which was reversible by reperfusion with heparin. Observations by freeze-fracture confirmed the similarity of the polycation-induced lesion to the epithelial changes in rat aminonucleoside nephrosis. Following exposure to polycations there was also "staining" of anionic sites on epithelial and endothelial cell membranes and glomerular basement membrane. Reperfusion of protamine-treated kidneys with heparin resulted in restoration of previously suppressed colloidal iron staining and the formation of spherical, electron-dense (heparin-protamine) complexes within the glomerular filter.
|
63,654
|
Hyperinsulinism of hepatic cirrhosis: Diminished degradation or hypersecretion?
|
The breakdown of proinsulin in the pancreatic beta cell yields insulin and C-peptide which are secreted in equimolar amounts. Unlike insulin, C-peptide is not degraded significantly by the liver, so that its measurement should give a better assessment of insulin secretion than estimation of peripheral insulin levels alone; particularly in the presence of hepatic dysfunction. Plasma C-peptide and insulin response to an oral glucose load have therefore been assessed in 14 cirrhotic and 7 normal subjects. Cirrhotic patients were divided into hyperinsulinaemic and normoinsulinaemic groups based on fasting plasma-insulin concentrations. Fasting blood-blucose and plasma-C-peptide concentrations were the same in normal and cirrhotic subjects, suggesting that basal pancreatic insulin secretion was the same in all subjects. Thus the C-peptide/insulin ratio was significantly decreased in hyperinsulinaemic subjects (2-13 +/- 0-31, compared with 4-63 +/- 0-48 in controls). After oral glucose, the two groups of cirrhotic patients showed the same glucose intolerance. C-peptide concentrations were also the same but insulin concentrations were markedly increased in the hyperinsulinaemic group. It is suggested that pancreatic insulin secretion is not increased in cirrhosis and that the peripheral hyperinsulinism is due solely to decreased hepatic insulin degradation secondary to either spontaneous portal-systemic shunting or to parenchymal damage.
|
63,653
|
Sequelae of concussion caused by minor head injuries.
|
Of 145 patients with concussion from minor head injuries admitted to the Royal Victoria Hospital, Belfast, over one year, 49.0 per cent had no symptoms, 38.9 per cent had between 1 and 6 symptoms, and 2.1 per cent had more than 6 symptoms about six weeks after the accident. There was significant correlation between a high symptom-rate at six weeks and positive neurological signs and symptoms at twenty-four hours. Post-concussion symptoms were more frequent in women, in those injured by falls, and in those who blamed their employers or large impersonal organisations for their accidents. The results suggest that both organic and neurotic factors are involved in the pathogenesis of symptoms at six weeks.
|
63,655
|
Autosomal recessive inheritance of susceptibility to tinea imbricata.
|
Familial distribution of chronic tinea imbricata in an untreated Melanesian population was consistent with a genetic predisposition to this disease. The pattern suggested that susceptibility to chronic Trichophyton concentricum infection is recessively inherited and controlled by genes at a single autosomal locus. In married couples there was no concordance of the disease above that expected by chance and the observed segregation of tinea imbricata accorded well with that predicted by the genetic hypothesis.
|
63,656
|
Subcutaneous fat in newborn infants of diabetic mothers: An indication of quality of diabetic control.
|
Biceps, triceps, subscapular, and suprailiac skinfolds were measured in 40 newborn infants of diabetic mothers. Maternal fasting blood-glucose and mean blood-glucose in the third trimester correlated significantly with neonatal skinfold thickness. Skinfold measurement, when compared with a reference range for gestational age, may be a convenient way of assessing one effect of maternal diabetes on the fetus. Gluteal adipose-cell diameter was measured in 31 infants of diabetic mothers. The fattest babies had the largest adipose cells and there was a significant positive correlation between maternal fasting blood-glucose and neonatal adipose cell diameter. These findings are consistent with the hypothesis that in diabetic pregnancy fetal hyperglycaemia and hyperinsulinism stimulate increased triglyceride synthesis in adipose cells and enlargement of adipose cells and lead to an increase in fetal subcutaneous fat.
|
63,657
|
Human arterial and venous tissues generate prostacyclin (prostaglandin x), a potent inhibitor of platelet aggregation.
|
Fresh rings of arteries and veins obtained from surgical specimens generated an unstable substance, prostacyclin (prostaglandinx, [P.G.X]) WHICH IS A POTENT INHIBITOR OF PLATELET AGGREGATION. The spontaneous generation of prostacyclin as well as its generation from exogenous arachidonic acid was inhibit by incubation of the tissues with a prostaglandin-synthetase inhibitor such as indomethacin, whilst the generation induced by prostaglandin endoperoxides was not. 15-Hydroperoxyarachidonic acid (a lipid hydroperoxide) inhibited the generation of prostacyclin in all three situations. It is postulated that prostacyclin is important for prevention of deposition of platelets on the vessel wall and that the inhibition or prevention of the generation of prostacyclin is important in the genesis of diseases, especially those in which increased lipid peroxidation occurs, such as atherosclerosis.
|
63,658
|
Radially oriented fibrin crystallisation. A new test for endotoxin sensitivity in man.
|
Radially oriented acicular crystalline aggregates could be induced by incubating heparinised blood with bacterial endotoxins. These aggregates did not appear in the blood of 37 healthy volunteers but were observed in the blood of 130 patients, predominantly those with vasculitis, psoriasis, and bacterial infections. Study of these asteroid structures, which resemble 'sunbursts', led to the view that they are oriented crystals of fibrin radiating from a central platelet mass undergoing lysis.
|
63,666
|
Social-services support for multiple sclerosis patients in West of Scotland.
|
A survey has been carries out of 104 patients with multiple sclerosis (m.s.) in West-Central-Scotland. All patients were living at home, and success of services to assist them in the community was examined. The partients were aged 16-65 years and had permanent disability, many being severely handicapped. Regular hospital follow-up was more common among the least disabled. 24 patients had never seen a social worker. Many patients had experienced problems with employment but 37 per cent of these had never registered with a disablement resettlement officer. After advice 10 additional patients applied successfully for an attendance allowance. Legislation requires local authorities to compile a register of the disabled and give information on services available to them. Only 19 patients were registered, however, and no one had received any information from a local authority. Many of these M.S. patients had failed to establish or maintain contact with available services. These results indicate a need for reorganisation of the support for the chronically disabled, possibly by setting up regular clinics for assessment and management, as recommended by the Tunbridge report (1972).
|
63,667
|
Outcome of pregnancy among women in anaesthetic practice.
|
A survey has been made of the outcome of the pregnancies of 5700 women doctors first registered in England and Wales in 1950 or later. Conceptions that occurred when the mother was in an anaesthetic appointment resulted in smaller babies, higher stillbirth-rates, and more congenital malformations of the cardiovascular system than the pregnancies of other women doctors. There was no significant difference in the spontaneous-abortion rate between the two groups. A pronounced effect of age on this rate was evident among all groups examined.
|
63,673
|
Oral cimetidine in severe duodenal ulceration. A double-blind controlled trial.
|
40 adult outpatients with active endoscopically proven duodenal ulceration, who would otherwise have merited elective ulcer surgery, entered a double-blind trial of either cimetidine (1g/day) or placebo. After twenty-eight days, 17 of 20 (85%) patients receiving cimetidine showed ulcer healing, compared with 5 of 20 patients receiving placebo (p less than 0.0005). Patients receiving cimetidine had significantly more pain-free days and pain-free nights than those receiving placebo. There was good correlation between ulcer healing and symptomatic relief (p less than 0.0005).
|
63,699
|
Neurological and phychometric studies in children surviving freshwater immersion accidents.
|
A study of the neurological and intellectual sequelae of childhood near-drowning is reported. Results are from a total population study, without selection, of all freshwater immersion accidents in which consciousness was lost in the water. Such accidents affected 56 children in the city of Brisbane and environs over the period 1971-75. 54 of these children have been re-examined medically and psychometrically. Over 95 per cent of children who survived such accidents were neurologically normal. The median i.q. of survivors was 110 (range 90-137), which is higher than that of the general population. There is a suggestion that visualmotor (performance)) skills are particularly vulnerable to freshwater immersion hypoxia. In 20 per cent of survivors subscale disparities between verbal and performance skills exceeded 15 i.q. points. No correlation between the post-immersion I.Q. and either estimated immersion-time or water temperature was demonstrated in this study. No long-term emotional or personality disorders were encountered. Uncommon gross clinical sequelae of prolonged immersion in fresh water included spastic quadriplegia and gross mental retardation. All children in this study were apparently dead at the moment of rescue; despite this, the prognosis of near-drowning in childhood is excellent
|
63,708
|
1,25-dihydroxycholecalciferol in hypoparathyroidism.
|
8 patients with hypoparathyroidism have been treated successfully with 1,25-dihydroxycholecalciferol (0-25-1-0 mug/day) for 4-24 mo. Normal serum-calcium levels were restored in all patients, but half the patients required supplementary oral calcium. Treatment reduced serum-phosphorus in all patients, but values remained high in 3, and the renal-tubular reabsorption of phosphate returned to normal in only 2 of the 8 patients. A comparison is made with the effects of oral therapy with massive amounts of calcium salts. The data obtained are discussed in relation to the probable mode of therapeutic action of 1,25-dihydroxycholecalciferol.
|
63,709
|
Dose-effect relation of cholestryamine in children and young adults with familial hypercholesterolaemia.
|
Twenty children and young adults with familial hypercholesterolaemia (F.H.), on a diet low in cholesterol and high in polyunsaturated fats, were treated with cholestyramine in a metabolic unit to determine the decrease in plasma cholesterol and low-density lipoprotein (L.D.L.) cholesterol in relation to drug dosage, pretreatment concentrations of cholesterol and L.D.L. cholesterol, and body-weight. When the dose of cholestyramine was increased in thirteen patients by 1 g/day up to 16 g/day, given twice daily, cholesterol and L.D.L. cholesterol fell within the normal range in eleven subjects (average dose, 7 g/day), and the response was directly proportional (P less than less than 0-001) to the pretreatment concentrations of cholesterol (r = 0-89) and L.D.L. cholesterol (r = 0-93) but did not correlate with body-weight. Plasma total cholesterol and L.D.L. cholesterol continued to fall and concentrations reached a plateau after which additional cholestyramine had no further effect (average dose, 11 g/day). The L.D.L. cholesterol regression line successfully predicted the dose required to reduce L.D.L. cholesterol concentrations in seven other patients. There was a significant decrease in mean serum-folate in female patients. It was concluded that the minimum effective dose of cholestyramine in young patients with F.H. can be predicted from the pretreatment plasma total and L.D.L. cholesterol and may be given twice daily.
|
63,711
|
Genetic factors in the development of chronic active hepatitis.
|
In 14 of 16 patients with chronic active hepatitis (C.A.H.) who did not have HLA antigens B8 and/or B12 an external triggering factor (drug or virus) could be demonstrated at onset of symptoms. In contrast external factors were involved in only 11 of 25 cases of C.A.H. in patients with HLA-B8 and/or B12. In the latter group antinuclear antibodies were less common in cases possible triggered by external agents compared with cases in which no such factor was demonstrated. The results suggest that there are at least two pathogenetically different types of C.A.H.---one genetically determined type in which no external factor is involved and in which autoimmune phenomena are common, and another type triggered by environmental agents and not involving predisposing genetic factors.
|
63,710
|
Plasma-exchange and immunosuppression in the treatment of fulminating immune-complex crescentic nephritis.
|
Nine patients with fulminating immune-complex crescentic nephritis were treated by a regimen of intensive plasma-exchange, steroids, and cytotoxic drugs. In five patients with severe renal failure there was early and rapid improvement in renal function; in one patient an early but extensive focal necrotising glomerulitis was arrested; in two patients improvement was delayed for 3 and 7 weeks and could not confidently be attributed to therapy; one patient, anuric at presentation, did not recover renal function. Follow-up renal biopsy specimens, obtained in three patients, showed no evidence of active disease. With the Clq-deviation test, circulating immune complexes were detected in five patients before treatment and had disappeared when renal function had improved and stabilised: these patients showed the best response to therapy. In three patients temporary withdrawal of plasma-exchange was followed by the reappearance of immune complexes in the circulation and was accompanied in two patients by deterioration in renal function; reintroduction of plasma-exchange was followed by elimination of immune complexes and further improvement in renal function.
|
63,713
|
Limitations of transcendental meditation in the treatment of essential hypertension.
|
20 hypertensive patients participating in a professionally supervised programme of transcendental meditation showed no significant change in blood-pressure after a 6-month study. Although there were small reductions in systolic blood-pressure and in pulse-rate early in the trial, these changes had disappeared by 6 months. At no time did the mean diastolic pressure fall significantly. Plasma-renin activity did not change during the study. It is concluded that while the general feeling of wellbeing experienced by most patients may provide a useful adjunct to conventional treatments, it is unlikely that transcendental meditation contributes directly towards the lowering of blood-pressure.
|
63,712
|
Behaviour in ferrets of swine influenza virus isolated from man.
|
After intranasal instillation into ferrets, the "swine" influenza virus A/New Jersey/8/76(Hsw1 N1) had a 50% minimal infectious dose similar to that of previously tested A/PR/8-A/England (H3 N2) recombinants virulent and attenuated for man. A/New Jersey produced only a mild upper respiratory tract infection. However, higher titres of virus were recovered from the lungs over a longer period than experienced previously with Asian and Hong Kong virus strains. There was a diphasic pyrexia the second and higher peaks of which correlated with peak titres of virus in lung macerates. These results suggest that A/New Jersey has a pneumotropic potential in ferrets and, if the animal model is valid, possible in man.
|
63,714
|
Myotonia precipitated by propranolol therapy.
|
A 39-year-old man with ischaemic heart-disease developed clinical myotonia while taking propranolol. The myotonia disappeared when administration of the drug ceased. The patient appears to have dystrophia myotonica which had not been evident before propranolol therapy.
|
63,715
|
Is peptic ulceration a hormonal disease?
|
The pathogenesis of peptic ulceration cannot be explained by an abnormal capacity to secrete acid, for ulcers develop in patients who secrete acid normally. Duodenal and gastric ulcers have a common cause. The location of an ulcer in each individual is primarily determined by his capacity to secrete acid at that time. There is a difference between the mechanisms which heal an ulcer and cure a patient of his disease. Procedures that reduce an individual's capacity to secrete acid, heal an ulcer by moving the focus of the ulcerogenic forces to a more proximal site. It is necessary to remove an antral factor if in addition the patient is to be cured of his disease. It is postulated that this antral factor is the gastrin (G17) which is released in abnormal amounts into gastric juice in patients with ulcers and with gastrinomas. The abnormal amount of G17 in gastric juice may be responsible for releasing abnormal amounts of G34 into the circulation from the duodenum and from gastrinomas. The abnormal release of gastrin develops as a result of an impaired response to duodenal acidification manifest in part by an impaired release of secretin. It is postulated that the abnormal stimulation of antral gastrin release may on occasions give rise to antral G-cell hyperplasia, and that the abnormal secretion of gastrin into gastric juice may on occasions give rise to gastrinomas. These abnormalities may cause ulcers by producing an uncontrolled secretion of acid and an abnormal exposure to bile.
|
63,716
|
A miniature syringe pump for continuous administration of drugs and hormones: The Mill Hill infuser.
|
A miniature syringe pump has been developed for intravenous or subcutaneous infusion of the many drugs and hormones which produce better therapeutic responses when continuously delivered at a controlled rate than by repeated separate injections. The infuser uses disposable plastic syringes and is designed for precise tamper-proof delivery of 2 ml/24 h or 2 ml/8 h with quartz-crystal control, unaffected bt the dose-rate can be precisely determined by prescribing solutions of appropriate strength.
|
63,723
|
Prolonged exposure to a stressful stimulus (noise) as a cause of raised blood-pressure in man.
|
Systolic and diastolic blood-pressure was significantly higher in 44 male industrial workers with a noise-induced auditory impairment (greater than or equal to 65 dB at 3000, 4000, or 6000 Hz) than in 74 males of the same age with normal hearing. Moreover, significantly more individuals with hypertension (resting recumbent blood-pressure greater than or equal to 160/100 mm Hg) were found in the group with noise-induced loss of hearing. It is suggested that replaced and prolonged exposure to a stressful stimulus (industrial noise severe and prolonged enough to cause a permanent loss of hearing at the relevant frequencies) may be a contributing factor to the rise in blood-pressure through a mechanism involving structural adaption of blood-vessels in response to repeated peaks of raised blood-pressure.
|
63,722
|
Abuse of solvents "for kicks". A review of 50 cases.
|
The deliberate inhalation of solvents "for kicks" is becoming more common among children and adolescents in the west of Scotland. 50 consecutive police cases of solvent abuse in Lanarkshire have been reviewed. Investigation of the 42 patients (40 male and 2 female) showed that "sniffing" was a group activity involving many adolescents aged 12-19 years, all of whom had a previous history of solvent abuse. Although some incidents were reported within school hours, 52% of referrals occurred after 6 P.M., with Mondays, Wednesdays, and Fridays being the commonest days for referrals. Of 4 cases sent to hospital, 2 required admission. A list has been compiled of the agents most frequently used for inhalation purposes and a simple screening procedure based on gas-liquid chromatography developed to detect their solvent components. This has been successfully applied to the detection of solvents in blood-samples from the patients referred.
|
63,743
|
B-lymphocyte alloantigens associated with multiple sclerosis.
|
6 B-lymphocyte alloantigens have been provisionally identified with lymphocytotoxic antisera reacting, after absorption, specifically with B but not T cells. 3 of these antigens appear to form part of an allelic series. The frequency of HLA and B-lymphocyte antigens was then studied in 59 patients with multiple sclerosis (M.S.). 1 of the B-cell antigens, BT 101, was found in 49 out of 59 patients (83%), compared with 10 out of 30 normal individuals (33%), giving a relative risk of 9-8 times to the association. 2 other B-cell alloantigens and HLA-B7 showed lesser but significant positive associations with M.S. Apart from providing possible clues to the pathogenesis of M.S., the association between BT 101 and M.S. may allow screening for susceptible individuals who are thought to be at special risk.
|
63,744
|
Effect of intermittent compression of the arms on deep venous thrombosis in the legs.
|
Despite the presence of venostasis in the legs, intermittent compression of the arms during and after surgery reduced the incidence of deep venous thrombosis (D.V.T.) in the legs to half that in control patients and maintained blood fibrinolytic activity at preoperative values. It is suggested that the release of fibrinolytic activators is essential to the prophylactic action of pneumatic leggings.
|
63,745
|
Treatment of hypersplenism by embolus placement in the splenic artery.
|
In a patient with liver cirrhosis and severe hypersplenism resistent to corticosteroids splenectomy was attempted but proved impossible. Embolisation of the splenic artery with tiny fragments of absorbable gelatin sponge induced gradual restitution of haematological function to normal after 6 wk. Abdominal pain, paralytic ileus of short duration, transient pyrexia, and pleural effusion ensued but were well tolerated. The patient has remained well, 2 1/2 mo later. It is suggested that this simple method may prove rewarding and could safely be used, if necessary, more than once in patients for whom other treatments are unsuitable or have failed.
|
63,746
|
Reconstitution of B and T lymphocyte function in severe combined immunodeficiency disease after transplantation with thymic epithelium.
|
A patient with severe combined immunodeficiency has been given a transplant of thymic epithelium obtained from short-term culture of normal human thymus. 4 wk after transplantation immunoglobulin was detected and the patient now has normal levels of the three main classes. Functional antibodies of four specificities have been detected. An increase in reactivity to allogeneic cells and phytohaemagglutinin has been observed, with an increase in E rosettes; a positive delayed skin test to candida antigen is now present. The patient has shown reversal of wasting and has been free of infection for 7 months since receiving the transplant. It appears that under certain circumstances thymic epithelium reconstitutes both T and B cell functions.
|
63,747
|
Islet-cell antibodies in diabetes mellitus.
|
Islet-cell antibodies (I.C.A.) were found in 38% (319/829) of insulin-dependent diabetic patients, in 5% (6/112) of insulin-independent diabetics, and in 1.7% (3/177) of non-diabetic subjects. In the insulin-dependent group I.C.A. were found in 85% of patients immediately after the onset of symptoms and they became less common as the duration of disease increased I.C.A. were equally common in both sexes and the decline in their prevalence was independent of age. The antibodies were directed against cytoplasmic components of islet cells but not against insulin itself. The appearance of I.C.A. probably follows cell damage occurring before the onset of symptoms. By contrast, thyroid and gastric autoantibodies were more common in older patients and females. There was no correlation between the presence of these antibodies and I.C.A. in patients with either diabetes of recent onset or longstanding disease.
|
63,748
|
Differential response of chlamydial and ureaplasma-associated urethritis to sulphafurazole (sulfisoxazole) and aminocyclitols.
|
91 men with non-gonococcal urethritis (N.G.U.) were randomly treated with either sulphafurazole (sulfisoxazole), 500 mg orally q.i.d. for 10 days, or an aminocyclitol (streptomycin or spectinomycin), 2 g intramuscularity for 1 to 3 doses at 12 h intervals. Initial urethral cultures were positive for Chlamydia trachomatis (C) in 36 (40%). Ureaplasma urealyticum (U) was isolated from the urethra or urine from20 (95%) of 21 White men in a first episode of N.G.U. who had negative chlamydia cultures. Sulphafurazole, active against C. trachomatis but not U. urealyticum in vitro, produced a clinical response in 7 of 7 men with C+U- N.G.U. and 5 of 19 with C-U+ N.G.U. (P less than 0-01). Aminocyclitols, active against U. urealyticum but relatively inactive against C. trachomatis in vitro produced a clinical response in 0 of 6 men with C+U-N.G.U., 9 of 11 men with C-U+N.G.U. from whom ureaplasma was eradicated (P less than 0-01), and 0 of 8 with C-U+ N.G.U. from whom ureaplasma was not eradicated. C+U+ N.G.U. responded poorly to both antimicrobials alone. These results support the aetiological importance of both C. trachomatis and U. urealyticum in N.G.U.
|
63,749
|
Subcutaneous infusion and intramuscular injection of desferrioxamine in patients with transfusional iron overload.
|
The effects of intramuscular injection and subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion were compared in eleven patients with thalassaemia major and one with congenital sideroblastic anaemia who were being maintained on regular blood-transfusions. Total (48-hour) urinary iron excretion ranged from 3-3 to 40-3 mg (mean 16-3 mg) in nine patients who received 750 mg D.F. intramuscularly before transfusion and from 3-9 to 32-3 mg (mean 11-9 mg) in ten patients who received D.F. by the same route after transfusion. In all 9 patients studied before transfusion, continuous subcutaneous infusion of 750 mg D.F. over 24 hours increased iron excretion by 61-5 to 135-8% (mean 101+/-25-4 S.D.%) compared with intramuscular injection of a similar dose. In the 10 patients studied after transfusion, the iron excretion produced by continuous subcutaneous infusion was from 18-9 to 213% (mean 128+/-74-3%) more than that produced by a single intramuscular injection of D.F. When the subcutaneous dose over 24 hours was increased to 1500 mg in six patients, 48-hour iron excretion ranged from 29-2 to 81-2 mg (mean 52-4 mg) and was increased by 80-2--794% (mean 429%) compared with the excretion when 750 mg was given by intramuscular injection. It is concluded that continuous subcutaneous infusion of D.F. produces more iron excretion in patients with iron overload than intramuscular injection. Providing a suitable portable pump can be carried by the patients, continuous subcutaneous infusion of desferrioxamine may prove a valuable means of preventing or treating iron overload in anaemic patients maintained on regular transfusions.
|
63,757
|
Bacteraemia in a London teaching hospital 1966-75.
|
Analysis of blood-cultures done at St. Bartholomew's Hospital over the decade 1966-75 has revealed a five-fold increase in the incidence of bacteraemia. This increase was particularly prominent in patients with non-malignant disease. The predominance of bacteraemia caused by gram-negative organisms declined in recent years, whereas bacteraemia due to gram-positive organisms, anaerobes, and Candida spp. increased. A recent increase in the number of blood-cultures performed was associated with the introduction of commercially prepared bottles. This led to a higher rate of investigation of patients who ultimately proved to have negative results, and also to a higher incidence of contamination which exceeded the positivity-rate.
|
63,800
|
Amputation of the toes for vascular disease: fate of the affected leg.
|
53 patients coming to amputation of one or more toes for the late results of degenerative vascular disease were studied prospectively. By a median time of thirteen months, 26 of the 53 had undergone a major amputation of the affected side. Diabetes was associated with the same prognosis as atherosclerosis obliterans uncomplicated by diabetes. A palpable pedal pulse or a functioning arterial reconstruction carried a virtual guarantee of success for the toe amputation. The presence of a popliteal pulse, however, was not associated with any better prognosis than the presence of a femoral pulse alone. Smoking seemed to exert little influence. With the passage of time, the major-amputation rate rose steadily, and by 3 1/2 years almost three-quarters of the patients had come to major amputation.
|
63,801
|
Small-bowel abnormalities in multiple sclerosis.
|
Jejunal biopsies were performed in 12 randomly chosen patients with multiple sclerosis. The jejunal mucosa was examined histologically, ultrastructurally, and by tissue immune techniques. Histology showed a normal mucosa in 7 patients, increased inflammatory-cell infiltration in 3, a partial villous atrophy in 1, and a subtotal villous atrophy in the remaining patient. Fine structural abnormalities were seen in 6 of 8 patients studied. These included microvillous changes, increase in theliolymphocytes and epithelial lysosomes, thickening of the connective tissue with or without collagen fibres, and numerous macrophages containing large amounts of membrane-bound electron-dense material. The latter was seen in 5 of the 8 mucosae examined.
|
63,799
|
Inappropriate antihypertensive therapy in the elderly.
|
Six symptomless patients aged 64-84 (mean 72) years received antihypertensive therapy from their family doctors. Pretreatment systolic pressures ranged from 160 to 220 mm Hg and disastolic pressures from 80 to 120 mm Hg. Within one week of starting therapy all six patients were admitted as emergencies with epidoses of unconsciousness. Admission systolic pressures ranged from 80 to 150 mm Hg and diastolic pressures from 50 to 90 mm Hg. Before admission each patient had experiences symptoms of postural hypotension and had become housebound. After antihypertensive therapy was stopped, one patient had a residual left homonymous hemianopia but the others recovered completely. A raised systolic and distolic pressure is common in the elderly; potent antihypertensive treatment may seriously impair the quality of life and is often unecessary.
|
63,802
|
Evidence that endogenous calcitonin protects against renal bone disease.
|
Plasma concentrations of calcium, phosphate, alkaline phosphatase (A.P.), immunoreactive calcitonin (iC.T.), and immunoreactive parathyroid hormone (iP.T.H.) were measured in fifty-two patients with chronic renal failure on maintenance haemodialysis. On the basis of a bimodal distribution of values for plasma-A.P. the patients were dividied into 2 groups. In those patients with normal A.P. concentratons as well as in twenty-eight normal subjects there was a positive correlation between iP.T.H. and iC.T. which was independent of plasma calcium or phosphate. Patients with increased plasma-A.P. had higher concentrations of iP.T.H., lower concentrations of iC.T., and showed a negative relation between the concentrations of the two hormones. It is suggested that a possible factor in the pathogenesis of renal bone disease is a failure to secrete C.T. in adequate amounts.
|
63,803
|
A simple method of estimating progression of chronic renal failure.
|
In 31 of 34 patients with chronic renal insufficiency caused by various diseaes, reciprocal serum-creatinine concentration declined linearly as creatinine concentration rose from a mean of 2-6 mg/dl to 14-8 mg/dl over an average of 71 months. These results indicate that in most cases reciprocal serum-creatinine declines linearly with time as chronic renal failure progresses. Analysis of this relation in individual patients gives an estimate of the progression of the disease, may help to determine the effects of therapy, and could be used to predict when dialysis will become necessary.
|
63,804
|
HLA-linked genetic control of host response to Mycobacterium leprae.
|
Non-random parental HLA-haplotype segregation is demonstrated in siblings with leprosy. A new method is described for the statistical analysis of non-random segregation among sibships of different sizes. Sibs with the same type of leprosy show a significant excess of identical HLA haplotypes. This is also true for families in which only tuberculoid leprosy is found, which is by far the commonest type in the population studied. However, sibs affected with different types of leprosy share a haplotype less often than expected. This indicates that both susceptibility to and type of leprosy are controlled by at least two HLA-linked genes. Our findings suggest that the equivocal results of previous population studies are due to differences of linkage disequilibrium between HLA-linked genes controlling the host response to Mycobacterium leprae and alleles of HLA A and B loci in various populations.
|
63,805
|
Prognostic significance of lymphocyte surface markers in adult non-Hodgkin's malignant lymphoma.
|
Neoplastic tissues from 75 adults with non-Hodgkin's malignant lymphoma were examined for B and T lymphocyte surface markers. All nodular lymphomas were B-cell type. Of 40 diffuse lymphomas, 23 were B, 5 were T, and 12 were "null" type. Patients with nodular lymphoma survived significantly longer than those with diffuse lymphoma (P = 0-00003). For patients with diffuse lymphoma, however, surface markers provide prognostic information not obtainable by histological classification as "poorly differentiated lymphocytic" or "histiocytic". Patients whose malignant cells had B markers survived significantly longer than those whose malignant cells had no markers (P=O-008). Survival of patients with diffuse lymphoma was best predicted by a classification utilising both surface markers and histological appearances. Differences in survival among patients with B-cell and "null" or T-cell lymphomas may relfect differences in sensitivity to specific drugs.
|
63,806
|
Rapid decrease in plasma-triiodothyronine during surgery and epidural analgesia independent of afferent neurogenic stimuli and of cortisol.
|
Changes in circulating triiodothyronine (T3), thyroxine (T4), binding of thyroid hormones to plasma proteins (resin-T3 test), cortisol, and glucose were evaluated in sixteen patients undergoing abdominal hysterectomy. In eight of the patients afferent neurogenic impulses from the surgical area were blocked during and after operation by epidural analgesia. These patients were pain-free, and the normal stress-induced increase in cortisol and glucose was abolished. During epidural analgesia and general anesthesia plasma-T3 fell rapidly and values in the hypothyroid range were found 6 hours after skin incision. Similarly, an increase in the resin-T3 test reflected decreased binding of T3 to plasma proteins. Plasma-T4 decreased slightly during surgery and epidural analgesia (as it does when other anaesthetics are given), but increased during general anaesthesia. These results indicated that the alterations in thyroid hormones and their binding to plasma proteins after surgery are not caused by a stress-induced increase in plasma-cortisol or by neurogenic afferent stimuli from the surgical area, factors which are both known to affect concentrations of other hormones.
|
63,807
|
Cell partition. A simple test for lymphocyte sensitisation.
|
An established method of investigating total surface charge on particulate materials has been applied to the detection of changes in surface charge on macrophages which are induced by supernatants from the interaction of sensitised lymphocytes and appropriate antigen. The method was studied as an alternative to the established but problematical macrophage-electrophoretic-mobility (M.E.M.) test for detecting such changes. This preliminary investigation suggests that the results from subjects with and without malignant disease differ significantly.
|
63,813
|
Mortality from pneumococcal meningitis.
|
The records of 207 patients with pneumococcal meningitis admitted to Ahmadu Bello University Hospital, Zaira, northern Nigeria, between February, 1971 and June, 1976 have been reviewed. Mortality was 51%. Death was more likely in patients with a short history, impaired consciousness on admission, and an associated pneumonia. Cerebrospinal fluid levels of protein, lactate, fibrin degradation products, and polysaccharide antigen were higher in patients who died than in survivors.
|
63,814
|
Outbreak of hospital infection with a strain of Staphylococcus aureus resistant to gentamicin and methicillin.
|
A previously unreported strain of Staphylococcus aureus, resistant to both gentamicin and methicillin, as well as other antibiotics, caused an outbreak of hospital infection involving 17 patinets and 8 staff. In this outbreak none of the patients had received previous aminoglycoside therapy. The epidemic strain was eliminated by the use of strict measures for the control of infection.
|
63,846
|
Maximum acid output and risk of peptic ulcer.
|
The relationship between the capacity to secrete acid and the risk of peptic ulcer has been examined prospectively in 114 healthy symptom-free students and retrospectively in 2361 patients with and without ulcers. The risk of ulcer was found to increase as te maximum acid output (M.A.O.) increased, and the risk of recurrent ulceration, after vagotomy and drainage for duodenal ulceration, was found to increase as the postvagotomy M.A.O. increased. The risk of recurrent ulcer, at any postvagotomy M.A.O., was always greater than the risk of ulceration in a healthy individual with an equivalent M.A.O.. The addition of an antrectomy to a vagotomy restored the risk of recurrent ulcer towards that of a healthy individual developing his first ulcer. The therapeutic benefit of adding an antrectomy to a vagotomy could not be attributed solely to its enhancement of the percentage reduction in M.A.O. from 65% to 95%. The major therapeutic effect of an antrectomy seems to be achieved independently of its action on M.A.O.
|
63,848
|
Remission of myasthenia gravis following plasma-exchange.
|
A course of daily plasma-exchange was undertaken in 3 patients with severe myasthenia gravis (M.G.) who had failed to respond to anticholinesterases, thymectomy, and steroids. In the 2 cases with acquired M.G., exchange was associated with an unequivocal improvement in muscle weakness and fatiguability, indicating that a humoral factor in plasma is directly concerned in causing the disorder of neuromuscular transmission. The improvement began within a few days of initiating exchange and continued for several days after exchange ceased. Preliminary evidence suggests that the beneficial effect can be maintained with subsequent immunosuppressive therapy. The patient with congenital M.G. failed to improve, suggesting that its pathogenesis may differ from that of the acquired disease.
|
63,847
|
Maximum acid output and position of peptic ulcers.
|
In a retrospective analysis of 2218 tests of gastric secretion 27% of patients with duodenal ulcers had an abnormal capacity to secrete acid. The abnormality was evident only in patients who had had symptoms for longer than three years, and was greatest in patients who had had symptoms for six to nine years. There was no significant difference between the capacity to secretic acid in patients who had symptoms of duodenal ulcer for less than three years and the capacity to secretic acid in normal controls. The tendency for the capacity to secrete acid to increase with duration of symptoms was also evident in patients with gastric ulcers. The positions in which ulcers were found were closely related to the maximum acid output (M.A.O.), and to the age of patients. The site of recurrent ulcers, after vagotomy and drainage, was also related to the M.A.O. after vagotomy. These influences of ageing and vagotomy on the site of ulcers can be attributed to their antecedent effect on the M.A.O. It is suggested that the capacity to secret acid alone is not responsible for the genesis of peptic ulcers but that it influences the position in which an ulcer may develop under the influence of an unknown ulcerogenic factor.
|
63,849
|
Low lead levels and mental retardation.
|
Borderline and mildly retarded children attending the hospital developmental evaluation clinic were divided into two groups on the basis of the presence or absence of a pred with a paediatric control group using blood-lead concentration as the independent variable. Children with a history of diagnosed lead posisoning were excluded from the study. The group of mentally retarded children "aetiology unknown" had statistically significantly raised blood-lead concentrations but the mentally retarded sample with "probable aetiology" showed no significant difference in lead concentrations from those of the normal controls. It is concluded that the association between lead and mental retardation extends over a much wider range than hitherto suspected and that the nature of this association is independent of a history of "encephalopathic" lead poisoning. It is suggested that physicians should consider raised lead levels in their examination of all children suspected of mental retardation and that the numerical definition of lead toxicity should be re-evaluated.
|
63,850
|
Penicillinase-producing Gonococci in Liverpool.
|
Gonococci, which had acquired a TEM-type of penicillinase widely distributed among gram-negative bacilli, appeared in February, 1976, and soon accounted for 9% of isolates at a clinic in Liverpool. In 45 patients infected by such gonococci, the frequency of complications did not suggest reduced communicability or invasiveness, and usual forms of treatment with penicillins always failed. Spectinomycin succeeded in 21 (95%) of 22 patients treated, blt tetracyclines succeeded in only 13 (68%) of 19. Appropriate laboratory tests for recognising penicillinase-producing gonococci must be used since such gonococci have already been transferred to other parts of the U.K. Penicillinase-stable cephalosporins were active in vitro and could prove to be the future treatment of choice.
|
63,851
|
Red-blood-cell composition in thyroid disease.
|
Eight red-blood-cell (R.B.C.) consitituents were measured in ten patients with hyperthyroidism and in ten healthy subjects. Only R.B.C. sodium ([Na]) and zinc ([Zn]) differed much between the groups. Therefore, only these variables were measured in a larger group of untreated hyperthyroid patients. The increase in. R.B.C. [Na] and decrease in R.B.C. [Zn] were confirmed. The R.B.C. [Na] and [Zn] were related to each other and to the plasma-thyroid-hormone concentration. However, more patients had low R.B.C. [Zn] (91%) than had raised R.B.C. [Na] (50%). Further studies suggest that the R.B.C. [Zn] lags behind the clinical response when these patients are treated. These results suggest that the measurement of R.B.C. [Zn] may have a role in the diagnosis of hyperthyroidism.
|
63,852
|
Rapid diagnosis of thyroid disease using carbonic-anhydrase immunoassay.
|
Erythrocyte carbonic-anhydrase-I (C.A.I.) concentration was measured by radial immunodiffusion in 30 thyrotoxic patients and 15 myxoedemic patients, the results being compared with those found in a control group of 90 euthyroid individuals. In thyrotoxicosis the erythrocyte-C.A.I. concentration was found to be below 10-29 mg/g haemoglobin, whereas the normal range varied from 11-1 to 22-5 mg C.A.I./g Hb. Low values were found in 4 patients with triiodothyronine(T3)-toxicosis. In myxoedema, the mean erythrocyte-C.A.I. concentration, though elevated at 20-37 mg/g Hb, fell within the normal range. In pregnancy, the erythrocyte-C.A.I. concentration rose with time, the mean value at tern being 20-6 +/-S.D. 3-3 mg/g Hb. In a group of women taking oral contraceptives, a low erythrocyte-C.A.I. concentration was noted--an effect which was most obvious among those taking low-oestrogen contraceptives. It is suggested that erythrocyte-C.A.I. estimation provdes a rapid screening test for thyrotoxicosis.
|
63,853
|
Antiviral activity in milk of possible clinical importance.
|
In human and in cow's milk an antiviral activity has been detected which does not seem to be related to antibodies or other known virus inhibitors. The antiviral activity lay in a relatively heat-stable macromolecule belonging to the non-fatty part of milk.
|
63,860
|
Coronary risk factors and socioeconomic status. The Oslo study.
|
Coronary heart-disease (C.H.D.) had been reviewed as a "manager's disease". However, deaths from C.H.D. are now said to be more common in groups from the lower social classes than in those of higher socioeconomic status. We have examined wheather these differences in C.H.D. mortality can be explained by differences in the conventional risk factors for C.H.D.
|
63,889
|
Transnasal transsphenoidal approach to the sella.
|
The transnasal transsphenoidal approach to the sella turcica has been refined and perfected through advances in medicine and technology. Originally performed for excision of pituitary adenomas, its present primary use is pituitary ablation is hormonally dependent diseases. Our study of 55 patients who have undergone this procedure during the years 1970-1975 demonstrates that this microscopic technique gives excellent exposure and visualization of intrasellar contents. Our method gives excellent exposure and visualization of intrasellar contents. Our method with several instrument modifications is discussed. It is technically an easy procedure with a minimum of morbidigy and mortality.
|
63,895
|
Phosphotungstic acid-iron-haematoxylin staining method for osteoid, boundary bone and bone components in paraffin sections.
|
A new staining technique which stains osteoid and bone tissue differentially and also demonstrates boundary bone, pathological osteoid and the changes in ageing, pathological and dead bone matrix in decalcified paraffin or low-viscosity-nitrocellulose bone sections was developed. This phosphotungstic acid-iron-haematoxylin (PTAIH) method is based on pretreating the sections with phosphotungstic acid followed by an iron alum mordant and staining in haematoxylin with subsequent timed differentiation, at certain stages of which the features listed above appear. Van Gieson's picrofuchsin is then used as a counterstain. After standard differentiation osteoid appears red in sharp contrast with the black bone, young and woven bone, old and lamellar bone, and allows one to demonstrate changes in stainability of diseased osteoid and bone matrix, and dead bone. With the differentiation done individually and interrupted at certain stages it is possible to distinguish between various bone components depending on the amount and quality of their in vivo mineralisation. Comparison with controls showed that in this respect the method is more sensitive than the curremt staining techniques of undecalcified bone sections since it demonstrates not only unmineralised and fully mineralised tissues but also shows the poorly calcified, demineralised and ill-calcified bone components. The advantages of the method compared with those using undecalcified sections are its simplicity, suitability for fixed and decalcified material in any unspecialised histological laboratory and the fact that osteoid and other bone components can be studied in sections of unlimited size and in undisturbed relationship to their surrounding soft tissues.
|
63,896
|
Methods of fixing, sectioning and staining amphibian eggs for cytological study.
|
A combination of methods for fixation (sublimate, cobalt nitrate, formaldehyde, acetic acid in water), inclusion (celloidin dissolved in methyl salicylate, paraffin-paraplast) and staining was used to make serial sections easy, to avoid clefts and to give a good picture of segmentation mitoses, as well as a good contrast of yolk and cytoplasmic components. Four methods of staining were used concerning the Urodele eggs: Safranin-methyl blue-orange G, safranin-picro-blue black naphthol (Curtis), safranin-violet crystal-orange G (Flemming) and Feulgen-methyl blue-orange G. The achromatic apparatus of the normal segmentation mitoses is clearly delineated and the relationships between astral fibers and yolk are different at metaphase and anaphase. By these methods, particularly suitable for demonstration of nuclei, cytoplasm and achromatic apparatus, the cleaving egg may be used as a test for the inhibition of achromatic apparatus and chromosome damage by antimitotic substances. The contrast between vitelline cytoplasm and cytoplasmic non-vitelline abnormal fibrillar systems, produced by transformation of astral and diastematic fibres, is made particularly evident by these methods of staining.
|
63,899
|
Evaluation of an integrated multi-media learning system.
|
Two teaching methods were compared: (1) the traditional way with textbooks, practical guidance, personal demonstration, and (2) an integrated multimedia system with text programme, slide-sound-show accompanying the experiment, and lecturer. Two samples of thirty-one students each were classified in twin groups by means of psychological tests. Both groups worked with the identical pretest/post-test and different training procedures. The integrated multi-media system produced highly significant more gain in the theoretical sphere, greater personal confidence, and lower experimental error. Furthermore positive attitude of the students towards the experiment was demonstrated. The improved performance was statistically proved by t-test and covariance analysis.
|
63,898
|
A lecture on lecturing.
|
There are major differences between a lecture and a paper for publication. Often the printed word is spoken at meetings, a kind of compulsive public reading which has robbed the lecturer of the chance of oratory and the audience of a little enjoyment. The simple fact is that although doctors read aloud badly (actors do this far better) most can learn to speak spontaneolsly and with animation; but this requires time and effort, both of which are donated in a miserly way. The successful lecturer is generous and considerate of his audience--a rare being at medical meetings.
|
63,900
|
A method of teaching epidemiology in the clinical setting.
|
It is important to provide an epidemiological presence when teaching clinical medicine to undergraduate medical students in order to supply the underlying facts about disease. A series of pictorial or tabular presentations which together make up a 'master set' of Data Boards has been designed to give the medical student a visual picture of epidemiology. Each Data Board is constructed in such a way that it can be readily interpreted by a medical student at the bedside or in similar situations to those where he is expected to interpret clinical signs and symptoms of disease. The present use of Data Boards in clinical teaching is described and suggestions for future applications are made.
|
63,903
|
[Pathological-anatomical findings in 70-102 years old Caucasians (author's transl)].
|
The macroscopic findings of 2385 autopsy protocolls of 70-102 year-old males and females were analysed for frequency and functional significance of diseases. 1. Severe coronary arteriosclerosis was found up to 60% of the cases, with increasing frequency in higher age groups. However decrease of acute myocardial necrosis was stated including the highest age group. 2. The mean values of heart weights decrease in the highest age groups. 3. While the frequency of arteriosclerosis in the cerebral arteries increases the frequency of ischemic lesions of the brain decreases. 4. Benign hyperplasia of the prostate is found in 85% of the cases. 5. 80% of the patients had severe substantial chronic pulmonary emphysema and acute tracheobronchitis. These pulmonary lesions are supposed to be the functionally most important disease in patients of old age.
|
63,902
|
The pathogenesis of amyloid deposition: a new hypothesis.
|
Amyloid proteins are probably derived from a variety of precursor glycoproteins. It is postulated that there may be at least two key events in the pathogenesisi of amyloidosis. The first is an increase in the load of glycoprotein being brought to a site of degradation. In the case of myeloma this might be in the form of excess immunoglobulin light chains. In the case of secondary amyloidosis the form taken could be enzyme-alpha-globulin complexes. The second is an inability of the degrading site to handle the arriving substrate at a sufficiently rapid rate, the rate limiting step being at some point along the degradation pathway. We postulate that an acquired enzyme deficiency prevents removal of the carbohydrate moiety of the presented glycoprotein. This results in the accumulation of a normal intermediate (amyloid protein) during the breakdown of the glycoprotein substrate. Evidence for the operation of these mechanisms is discussed and their detailed nature and implications considered.
|
63,905
|
Electron-microscopic identification of infectious particles of lymphocytic choriomeningitis.
|
LCM virus, strain WE--grown on L cells--and labeled with 3H-uridine was centrifuged to equilibrium in a sucrose density gradient and examined in fractions for infectivity, incorporated radioactivity, and electron-microscopic features. The peak of infectivity is congruent with the one of radioactivity (density = 1.17 g/ml). LCM virus specificity of the radioactive peak was proved by precipitation of the radioactivity with anti-LCM virus antiserum. The peak fractions showed an abundance of 106 +/- 14 nm (1s) particles. They could be agglutinated with specific anti-LCM virus antiserum but not with antiserum directed against the histocompatibility (H-2) antigens of L cells.
|
63,906
|
Serum protein electrophoresis (SPE) and immunoglobulin levels in breast carcinoma.
|
Serum protein electrophoresis (SPE) and immunoglobulin levels were studied in 50 patients with breast carcinoma before therapy (17 with stage I disease; 18 stage II; 15 stage III or IV), and in 55 patients after primary lesions were surgically removed and gave no evidence of recurrence. The most consistent and statistically significant abnormalities observed on SPE were those of albumin, globulin, and alpha-2 globulin. Patients who were free of disease during follow-up examinations had higher albumin and lower globulin and alpha-2 globulin levels than those with advanced breast cancer (P = 0.003, P = 0.03, and P = 0.001 respectively). There was no difference in concentrations of immunoglobulin G, A, or M among the 5 groups. Routine laboratory tests of hemoglobulin, lymphocyte count, calcium, alkaline phosphatase, creatinine phosphokinase, lactic dehydrogenase, and transaminase also did not differ among the groups, but carcinoembryonic antigen was significantly elevated in patients with stage III and IV disease.
|
63,910
|
Tissue specificity of nonhistone proteins from human chromatin.
|
Nonhistone proteins were isolated from human placental and tonsillar chromatins. Antiserum was prepared against a complex from some nonhistone proteins and DNA (NP-DNA) from placental chromatin. With the help of polyacrylamide gel electrophoresis and immunological methods the tissue specificity of human chromatin nonhistone proteins was established. The described organ immunogenic specificity of the complex of DNA and nonhistone protein (NP-DNA) from human chromatin is in accordance with data published on similar complexes from different animal organs. Besides, it is shown that shearing of chromatin leads to large chifts in NP-DNA concentrations required for maximum complement fixation in the presence of the prepared antiserum. This may probably be due to a damage of certain chromatin super structures which involve some of the nonhistone proteins and DNA sequences from both the more condensed and less condensed parts of chromatin.
|
63,914
|
Effect of a digitalis drug on ventricular premature beats.
|
To determine the efficacy of digitalis drugs in suppressing ventricular ectopic activity, 142 patients with frequent (greater than 1 per minute) ventricular premature beats underwent acetyl strophanthidin tolerance testing. In 65 patients (46 per cent), frequency and grade were reduced during testing. In 37 (26 per cent), the ectopic activity remained unaltered; frequency increased during testing in the remaining 40 patients (28 per cent). In the group with a suppressive effect, ventricular premature beats decreased by 82 per cent, with complete abolition of arrhythmias in 46 per cent. The three groups were not distinguishable clinically by either the type or the extent of heart disease. The antiarrhythmic action of acetyl strophanthidin did not appear to depend upon its positive inotropic action. In some patients it appears to be due to an indirect reduction of Purkinje-fiber automaticity resulting from enhanced vagus-nerve activity that thereby lessens adrenergic tone on the heart.
|
63,913
|
Biochemical and electron microscopical evidence for the presence of oncorna viruses in spleen tissue from two patients with haematological malignancies.
|
In extracts of spleen tissue from two patients with haemotological malignancies an RNA dependent DNA polymerase was found in particles with a density of 1.16, that is at the density of oncorna viruses. After treatment with noniomic detergents the enzyme activity was found in particles with a density of 1.23-1.24, similar to the density of oncorna viral cores. A simultaneous detection test with this core fraction material for 70 S RNA and RNA dependent DNA polymerase was positive for both patients. Electron microscopical inspection of the material with a density of 1.16 revealed immature C-type virus like particles, various stages of maturing particles and a number of particles resembling mature C-type oncorna viruses. In two normal spleens from patients with carcinoma of the colon and oesophagus respectively and in three spleens from patients with no history of malignancy no RNA dependent DNA polymerase was found. Material from one normal spleen was examined in the electron microscope and no virus-like particles were seen.
|
63,921
|
Generation of an esterolytic and kinin-forming kallikrein-alpha2-macroglobulin complex in human serum by treatment with acetone.
|
Kinin-forming and esterolytic activity in human citrate plasma has been activated by treatment of the plasma with acetone. By far most of the esterolytic activity if not all of it was recovered in an alpha2-macroglobulin (alpha2M) kallikrein complex (SI) which was characterized and purified by chromatography. Little if any esterolytic activity was present which could be ascribed to free plasma kallikrein. The alpha2M-kallikrein complex had kinin-releasing activity though much less than free plasma kallikrein, relative to esterolytic potency. This explains that a considerable fraction of the kinin-forming potential of acetone-activated plasma resides in free plasma kallikrein although it represents only a very small portion of the total kallikrein store. Like free plasma kallikrein the alpha2M complex releases kinin from LMW-kininogen less efficiently than from HMW, in systems of purified components. In whole plasma, the efficiencies change: whereas plasma kallikrein is rapidly inactivated by endogenous inhibitors, the alpha2M complex is protected from further inactivation and capable of releasing kinin continuously if slowly, attacking also LMW-kininogen after HMW-kininogen has been consumed by free kallikrein. While the alpha2M-complex in this respect differs functionally from free plasma kallikrein and explains earlier observations suggesting the presence of two kininogenases, it seems doubtful now that two truly different kininogenases exist in human plasma. The results suggest that acetone predominantly inactivates full inhibitors of kallikrein such as C1INH whereas alpha2M is somewhat more resistant and (pre-)-kallikrein even more. Depending on the time and temperature of acetone treatment one obtains more or less total kallikrein and varying proportions of free to bound enzymes. It is likely that acetone does not turly trigger an activation of prekallikrein but supports spontaneous activation by slowing down the control of the feedback reinforcement of this activation, by damaging inhibitors.
|
63,926
|
Amniotic fluid tests for fetal maturity in normal and abnormal pregnancies.
|
The lecithin-sphingomyelin (L/S) ratio is acknowledged to be superior to most procedures for predictinf fetal lung maturity in normal pregnancy. In complicated gestations, however, errors have been reported. This study involves 686 normal gestations and 389 pregnancies complicated by fetomaternal diseases. The L/S ratio, creatinine level, and percent of fat-staining cells were measured in samples of amniotic fluid from these patients. The results showed good correlation of all three tests with fetal maturity as measured by weight, Dubowitz criteria, and incidence of respiratory distress syndrome in the normal patients. In the complicated pregnancies, however, the creatinine was unacceptable in up to 30% of the cases. The L/S ratio likewise decreased in accuracy for all parameters of fetal maturity measured. The Nile blue staining of the fetal cells appeared to be the most consistent technic in these cases. A fetal maturity battery comprised of these three assays and other methods of assessing fetal health is advocated in pregnancies complicated by certain disease states.
|
63,927
|
Amniography for the early detection of neural tube defects.
|
Among the methods available for the midtrimester diagnosis of neural tube defects, it has been suggested that amniography be used to determine the presence of meningomyelocele. Twelve studies are reported in which the procedure was utilized. In 3 cases, a neural tube defect was present but was not detected by this method. The experience reported here challenges the value of this procedure and suggests that it should be evaluated further by utilizing it in cases where a positive diagnosis has been made by other methods and pregnancy termination is to be performed.
|
63,928
|
Nile blue and fetal maturity. Further investigations.
|
The consistency of results using Nile blue staining of fetal cells in amniotic fluid to estimate fetal maturity has been demonstrated. Recently, evidence to support this method has been published from this laboratory. Several biochemical and technical factors were cited as important to the success of the method. This report deals with further testing of several Nile blue dyes (hydrochloride and sulfate) necessitated by changes in production and federal regulation of this compound. The results show Nile blue hydrochloride (HCl) to be the most superior dye regardless of color index. Buffered solutions (6.6) of Nile blue A (sulfate) improve its performance, but not to levels demonstrated by the HCl preparation. Storage at room temperature adversely affects each dye; however, the sulfate variety appears to be the most unreliable under these circumstances. For best results, it is recommended that Nile blue HCl be used and the solution (buffered or normal) be kept refrigerated.
|
63,929
|
Phytohemagglutin-induced lymphocyte transformation in oral contraceptive users.
|
Phytohemagglutin (PHA)-induced lymphocyte transformation (PILT) was determined in 217 women taking oral contraceptives and 203 control women by means of the uptake of 3H-thymidine into DNA of lymphocytes cultured in heterologous serum. Depressed PILT responses were observed in oral contraceptive users as compared with age-matched controls, and the magnitude of depression correlated with the duration of oral contraception and was inversely related to the clinical progestagenic potency of the component steroids. An additional group of 21 women, tested within 1 year (mean 3 months) of cessation of oral contraception, showed persistent depression of PILT responses. Suppression of lymphocyte transformation in autologous as compared with homologous, normal serum suggests that serum inhibitory factors amy be important. We found no evidence for a direct suppressive in vitro effect of synthetic estrogens and gestagens. The prevalence of autoantibodies in oral contraceptive users was similar to that in control subjects.
|
63,931
|
[New experiences with bleomycin].
|
26 patients all with squamous call carcinoma of the head and neck were treated primarily with Bleomycin (maximal dose 300 mg by i.v. injections of 15 mg every second day). In 10 of the patients a significant regression of the tumor was achieved. In one particular case no histological evidence of tumor could be found. The expected side effects of Bleomycin were observed. Two patients died of heart-lung failure. Histological examinations showed signs of cytostatic pneumopathy.
|
63,933
|
Tumoral drugs as possible blastogenic agents the problem of anti-blastic medication.
|
The author studies the possible transplacentary carcinogenic drugs used in human therapeutics; the study is of an experimental nature, the pregnant mother rat being injected at the 20-21st days of gestation with double the kg/day dose used in human therapeutics. A total of 1,264 rats (Wistar) were utilized, careful note being made of the possible appearance of tumors throughout the lives of the animals. The products and tumoral percentages, both benign as well as malignant, were as follows: Oncotiotepa (0%); Daunoblastine (3.3%); Vinblastine (9%); Bleomycine (12.8%); 5-Fluoro-Uracil (12.87%); Lyovac (cosmogen) (16.6%); Genoxal (17.14%); and Natulan (37.42%). The benign forms predominated in all the tumors produced, but with some of the drugs the malignant varieties produced were made as 39.3% of the tumors. The location and type of tumors were variable; there being cutaneous, glandular, mammary, hepatic, renal, and tumors of the nervous system; there were also tumors of epithelial, connective and nervous variety.
|
63,934
|
Silver deposition in mouse glomeruli.
|
Administration of 6 mM silver nitrate in the drinking water of mice resulted in deposition within the glomerular basement membrane of silver granules which were detected on electron microscopy after 12 days. Larger aggregates were detected in the basement membrane and mesangium when silver ingestion was extended to 14 weeks. The silver deposits did not alter significantly over a period of 21 weeks after silver nitrate ingestion was stopped.
|
63,937
|
Morphological and immunological evidence of coagulopathy in renal complications of pregnancy.
|
Renal biopsies in 14 patients with P.E.T. or eclampsia showed constant I.F. reactions for IgM and fibrin, with frequent reactions for C1q and C3. The glomeruli showed reversible mesangial proliferation and swelling, with characterictic E.M. deposits, and segmental lesions were present in seven patients. Similar I.F. reactions occurred in three other patients with clinical diagnoses of P.E.T. whose biopsies demonstrated coexistent glomerular disease. Serum complement studies showed a significant rise in C3 in the third trimester of normal pregnancies and a further significant elevation in C1q and C3 in the third trimester of a series of unselected P.E.T. patients. In contrast, four patients from the biopsy series with eclampsia or severe P.E.T. showed profound depression of serum C3 and C4, at the time of maximum clinical severity, which was shown to return to normal in two patients. The I.F. findings confirm those of Petrucco et al (6), and, with the other data, suggest that immune-complex deposition and activation of the classical complement pathway could interrect with intravascular coagulation to produce the glomerular lesions of P.E.T. and eclampsia.
|
63,941
|
Lipofuscin in neuronal aging and diseases.
|
The increasing intraneuronal accumulation of lipofuscin has been linked to the aging process by a striking linear correlation between the degree of accumulation and chronological age. It has been established that age pigments are soluble in polar and nonpolar solvents; the pigment is autofluorescent and stains with PAS, Sudan black B, Nile blue osmic acid and ferric ferricyanide techniques. Whether all pigments exhibiting these properties are identical, or at least closely related, regardless of the surrounding tissue, animal species and age of the individual, is debatable. Pigment formation has been demonstrated in young and aged animals as well as in individual subjected to experimental stress and to dietetic and environmental interference. Electron microscopic studies in animals have shown a considerable variability in the fine structure of individual lipofuscin granules but the presence of "lucent vacuoles" surrounded by a unit membrane is one of the characteristic features of neuronal lipofuscin in the aged. Recently, electron microscopy, utilizing the freeze-etching technique, has provided convincing evidence which disproves the earlier view that lucent vacuoles are the remnant of lipid material dissolved and removed during the preparation of the tissues for microscopic examination. These vacuoles have also been demonstrated in freshly frozen material not previously fixed or immersed. Vacuolated pigment granules occur earlier in the area postrema than in other regions of the rat brain (Hasan and Heyder 1974). Regional differences in the time sequence of pigment deposition are present.
|
63,942
|
Blood groups changes in preleukemic states.
|
Modifications of blood groups in the course of malignant hemopathies are related to the disease itself and appear to be essentially clonal. They refer not only to the glycolipidic ABH and associated antigens, but also to other blood group systems or other genetic markers. These multiple abnormalities are observed in the preleukemic states as well as in the actual leukaemias. Similar but limited to one genetic unit abnormalities have been noticed among apparently normal subjects, especially in the aged. The various modifications observed are indeed related to the genetic function, and the clonal character is in favor of this assumption. The evidence of abnormalities affecting two genetic systems which are linked ABO and AK is a further argument supporting this hypothesis. Furthermore, the distribution of immunoglobulin marker abnormalities corresponds to that of one of the haplotypes of the Gm genotype. Finally, we were able to demonstrate that the glycosyltransferase itself is abnormal too, in the case of ABH antigen abnormalities. In all the cases investigated to date, when apparently new characters seemed to be observed, they are in fact unconverted substrates, which are to be compared to the carcinoembryonic antigens.
|
63,943
|
Problems relating to immunoselection of leukemias.
|
Problems relating to immunoselection of neoplastic, in particular leukemic, cell lines are reviewed. Since there is ample evidence that specific immune reactions of the host against malignant neoplastic cells do occur, it becomes important to consider the effectiveness and the relevance of immunity in suppression or elimination of neoplastic growth. Emphasis is placed on experimental results obtained in syngeneic tumor-host combinations, because they more closely resemble the situation of spontaneous tumorigenesis or leukemogenesis than xenogeneic or allogeneic model systems. Studies of types of neoplasia observed in cases of human immunodeficiency syndromes offer an important insight into problems involved in immunoselection of leukemic cell lines: the marked predominance of leukemias and lymphoreticular neoplasias in immunodeficient patients invites speculation on both the mechanisms of leukemogenesis and the relative importance of the immune system in eliminating malignant neoplastic cells.
|
63,947
|
Binding of triton X-100 to diphtheria toxin, crossreacting material 45, and their fragments.
|
Binding of the nonionic detergent [3H]Triton X-100 by diphtheria toxin, by the nontoxic serologically related protein crossreacting material (CRM) 45, and by their respective A and B fragments has been studied. If first denatured in 0.1% sodium dodecyl sulfate, all of the proteins with the exception of fragment A bind increasing amounts of Triton X-100, reaching a maximum of more than 40 mol bound per mol of protein when the detergent concentration exceeds its critical micelle concentration. No measurable amount of Triton X-100 is bound by native toxin or its A fragment of any concentration of the detergent. Undenatured CRM45 or its B45 fragment, on the other hand, readily became inserted into Triton X-100 micelles when the detergent reaches its critical micelle concentration. The results show that the toxin molecule contains a hydrophobic domain located on the portion of the B fragment that is linked to A. This region is masked in native toxin. Based on these findings, a model is proposed to describe how fragment B facilitates the transport of the enzymically active hydrophilic fragment A across the plasma membrane to reach the cytoplasm.
|
63,948
|
Analysis of HeLa cell hypoxanthine phosphoribosyltransferase mutants and revertants by two-dimensional polyacrylamide gel electrophoresis: evidence for silent gene activation.
|
The spot corresponding to hypoxanthine phosphoribosyltransferase (HPRT; IMP:pyrophosphate phosphoribosyltransferase, EC 2.4.2.8) has been identified in two-dimensional polyacrylamide gels of HeLa cell extracts. This spot is absent in gels of 24 HPRT dificient mutants. A missense mutant displays a new HPRT spot at the same molecular weight but different isoelectric focusing position. Five independently isolated revertants of the missense mutant display spots corresponding to both the wild-type and mutant proteins indicating that they synthesize HPRT from two separate genes. If the missense protein is synthesized from a mutated form of the initially active HPRT gene, then wild-type HPRT protein in the revertants must be snythesized from a newly activated but prevously silent wild-type gene. The newly activated gene in the revertants of the missense mutation appears unstable producing a high frequency of spontaneous HPRT mutants.
|
63,949
|
Bvr-1, a restriction locus of a type C RNA virus in the feline cellular genome: identification, location, and phenotypic characterization in cat X mouse somatic cell hybrids.
|
Somatic cell hybrids were constructed between BALB/c-RAG mouse cells and feline lymphoma cells by the hypoxanthine-aminopterin-thymidine selection scheme. RAG cells spontaneously produce an endogenous B-tropic type C virus. Cat-mouse hybrids preferentially segregate feline chromosomes and retain murine chromosomes-demonstrable by karyotypic and isozyme analyses. Despite the presence of the complete mouse genome, including the viral genome, virus production was diminished to 1-5% of the levels observed in RAG parents based upon particle-associated RNA-dependent DNA polymerase (reverse transcriptase) activity in the culture fluid. Thirty-seven hybrids made on four different occasions had suppressed virus levels, and no hybrids expressed parental virus levels. Reverse selection experiments on 6-thioguanine demonstrated that a restriction gene, tentatively named Bvr-1, was linked to the feline structural genes for hypoxanthine phosphoribosyltransferase (IMP:pyrophosphate phosphoribosyltransferase; EC 2.4.4.8) and glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate: NADP+ 1-oxidoreductase; EC 1.1.1.49) in cats, probably on the X-chromosome. The genetic mode of action of Bvr-1 is trans dominant in restriction of murine leukemia virus. The restriction locus results in a block late in virus maturation but prior to release, since expression of antigens for viral structural proteins and matrue budding particles is apparent on surfaces of restriced hybrid cells but not in high-speed pellets from culture fluid of restricted cells.
|
63,950
|
Antiviral effect on MS-2 coliphage obtained with a synthetic antigen.
|
The coat protein of bacteriophage MS-2 was cleaved with cyanogen bromide to yield three fragments, possessing the sequence 1-88 (P1), 89-108 (P2), and 109-129 (P3), respectively. The mixture of peptides P2 and P3, which could not be separated, was found capable of inhibiting the neutralization of the phage by antiserum to the whole MS-2. The peptides corresponding to P2 and P3 were therefore synthesized. The synthetic P3 had no capacity to interfere with neutralization of MS-2, not did its macromolecular conjugate with multichain poly(DL-alanine) elicit neutralizing antibodies. On the other hand, the synthetic P2 was very efficient in inhibiting the inactivation of the phage by the antiserum against phage. Furthermore, a synthetic antigen prepared by attachment of P2 to multichain poly(alanine) incuded antiserum in rabbits that was capable of neutralizing MS-2 activity almost as efficiently as the antiserum prepared against the intact coat protein. This inactivation is specific, because it can, in turn, be totally inhibited by P2 peptide.
|
63,951
|
Immunological crossreaction between alpha-fetoprotein and albumin.
|
Alpha-fetoprotein (AFP), a fetal protein associated with certain tumors, and serum albumin did not corssreact immunologically in native form. Unfolding of their polypeptide chains by reduction of the disulfide bonds followed by carboxamidomethylation produced derivatives with immunochemical properties different from those of the native proteins. Precipitating reactions and radioimmunoassays preformed with antibodies to such unfolded derivatives showed strong crossreactions between albumin and AFP. These assays were found to lack species specificity: AFPs and albumins from different species were equally active. Several other proteins unrelated to AFP or albumin did not react or reacted much less in these assays. These results support the conclusions derived from recent sequence data that AFP and albumin are structurally related and have a common ancestral gene.
|
63,952
|
Human alpha-fetoprotein as a modulator of human lymphocyte transformation: correlation of biological potency with electrophoretic variants.
|
Human alpha-fetoprotein (HAFP) isolated by immunoadsorbent column was shown to suppress the mitogenic response of human lymphocytes to phytomitogens, antihuman thymocyte antiserum, and the mixed lymphocyte culture. HAFP isolated from the sera and ascitic fluid of five hepatoma patients, and from fetal liver, varied in biological potency over three orders of magnitude. Extended agarose gel electrophoresis and crossed immunoelectrophoresis demonstrated three molecular species of HAFP. Quantitation of the three species revealed a correlation between the relative amount of the most negatively charged species and biological potency. Treatment of HAFP with neuraminidase to remove completely sialic acid residues did not alter the biological potency, but converted the three species to two species having slower electrophoretic mobilities. We conclude that differences in sialic acid content are only partly responsible for the microheterogeneity demonstrated by HAFP, and that variability in another charged moiety is also present. Variation in the relative proportions of the different molecular species of HAFP may be important in the regulation of its immunosuppressive properties.
|
63,953
|
Simultaneous detection of reverse transcriptase and high molecular weight RNA in tissue of patients with Hodgkin's disease and patients with leukemia.
|
Complexes of high-molecular-weight RNA and reverse transcriptase (RNA-dependent DNA nucleotidyltransferase) have been detected in 14(77.8%) of 18 spleen from patients with Hodgkin's disease and in all samples tested of peripheral leukocytes and spleens from leukemic patients. The enzyme and its template are localized in a particle having a density between 1.16 and 1.19 g/ml. These observations describe characteristic features of RNA tumor viruses.
|
63,957
|
Growth parameters of the hairless mouse epidermis after bleomycin treatment: possible interaction with epidermal chalones.
|
Hairless mice were given two injections of 2 mg bleomycin i.p. on two successive days. By a stathmokinetic method, micro-flow fluorometry and autoradiography, many kinetic parameters were measured. Bleomycin affected cell proliferation in epidermis by depressing the number of cells in and the passage of cells through the different cell cycle phases, i.e. S, G2 and M in a biphasic manner. The time between the two minima corresponded to the mean generation time of the basal cells. Skin extracts produced from animals at different time intervals after the bleomycin injection show that bleomycin interferred only slightly with the G1-chalone, but had a more pronounced effect on the content of G2 of the skin, increasing and reducing the chalone effect in a biphasic manner. The study gives some support to the theory that the particularly good effect of bleomycin in squamous cell epithelium may be due to an interference of bleomycin with keratinization and chalone production. The protein synthesis showed only a minimal depression where the kinetic parameters were heavily depressed.
|
63,962
|
Structure and action of bleomycin.
|
The structures of bleomycins and of other bleomycin-phleomycin group of antibiotics were described. The activity of bleomycins and their derivatives in causing strand scission of SV40 viral DNA suggests that the beta-aminoalanine amide moiety and the carbamoyl group are involved in this reaction. More than one guanido group in the terminal amine of bleomycin-phleomycin group antibiotics caused irreversible renal toxicity in dogs. Pulmonary toxicity varied depending on the terminal amines. A bleomycin-inactivating enzyme which distributes widely in animal cells was shown to be a new aminopeptidase B which hydrolyzes beta-aminoalanine amide group. At least one of the reasons for activity against squamous cell carcinoma was shown to be due to the lower content of this enzyme. The inhibitor of this enzyme was synergistic to bleomycin in inhibiting growth of cells, thus suggesting the intracellular action of this enzyme. Selected for further study from the bleomycins containing various terminal amines, bleomycin 5033 which showed the same activity against squamous cell carcinoma in mouse skin as the bleomycin used at present and lower toxicity than the latter, and bleomycin A5196 which showed stronger activity and stronger toxicity but lower lung toxicity than the latter.
|
63,965
|
Importance of experimental data for the improvement of the therapeutical effect of bleomycin.
|
The intimate mechanism of action of bleomycin has been extensively studied at molecular and cellular level. From the analysis of dose-response curves, different hypotheses have been formulated, and the importance and the extent of DNA repairability has been emphasized in correlation with the different phases of the cell cycle. Sensitivity to bleomycin depends on the fixation of DNA damage which occurs when damaged sites become involved in replication before they can be repaired.
|
63,968
|
Bleomycin effects on malignant tumors of the male genitalia.
|
Bleomycin was applied alone or in combination with actinomycin D, vinblastine, radiation and/or surgery in cancer of the penis (6) and testis (6). In early stages of penile cancer (T2 N0 M0) a total response was noted. The failure in advanced stages is discussed. In terato-, embryonal- and choriocarcinomas of the testis (T2-4 N0-2 M0-1) remarkable responses of short and long duration were observed in all patients. The reasons for different biological action are discussed.
|
63,969
|
Effect of bleomycin on DNA, RNA, protein, chromatin and on cell transformation by oncogenic RNA viruses.
|
Bleomycin (BLM) exclusively affects thymidine-containing compounds such as DNA and polydeoxyribonucleotides by releasing free thymine and leaving aldehyde functions. Molecular morphology and base sequence of the DNA strongly influence BLM activity. High BLM concentrations, besides modifying DNA into oligothyminic or athyminic nucleic acids, cause strand scissions. Enzymatic DNA and RNA synthesis is strongly influenced by BLM. The inhibition in DNA-dependent DNA polymerase and DNA-dependent RNA polymerase assays is of the non-competitive type. Protein biosynthesis in in vitro systems is not affected by BLM even at high concentrations. BLM turns out to be a strong inhibitor of DNase I and of DNase II; the inhibition is of the competitive type. The enzymatic activities of nucleases using RNA as substrate (RNase A, RNase B, Rnase T1, venom phosphodiesterase I and spleen phosphodiesterase II) are not influenced by this antibiotic. The antibiotic reduces cell proliferation (L5178y mouse lymphoma cells) in vitro in low concentrations by cytostasis and at higher concentrations by cytotoxicity. In BLM-treated L5178y cells, DNA synthesis is strongly reduced, while RNA and protein synthesis are not affected. In vivo, using growing quail oviducts, cell proliferation and cytodifferentiation are markedly inhibited after BLM treatment. This is attributed to the observed inhibition of DNA synthesis. RNA and protein synthesis as well as gene expression are not influenced by BLM under the conditions used. The selective inhibition of DNA synthesis in vivo may be caused by the following mechanisms: (1) competition of BLM with RNA; (2) blocking of the accessibility of DNA in chromatin to BLM, and (3) dependence from the repair processes. BLM inhibits growth of sarcomas, induced by oncogenic RNA viruses in vivo; well-developed tumours show regression after BLM treatment. Transformation of chick embryo fibroblasts by oncogenic RNA viruses in vitro and growth of these viruses is blocked by BLM; the most sensitive period for BLM inhibition is the time during the first period (integration of viral genome into cellular genome?) after infection.
|
63,970
|
Actions of bleomycin on DNA ligase and polymerases.
|
Bleomycin inhibited the ligase, which was partially purified from rat ascites hepatoma, AH-130, even at a concentration as low as 0.01-1 mug/ml. The DNA degraded by bleomycin was not repaired by ligase. Therefore, it was suggested that bleomycin at higher concentration produced strand scission of DNA, which could not be repaired by the ligase, and at lower concentration inhibited the ligase reaction presumably by binding to DNA strand or to ligase. Also, the specificity of inhibition by bleomycin on the DNA polymerase of oncogenic RNA virus was tested, comparing with the four kinds of DNA polymerases extracted from the spleen of mice infected with Friend virus. Three kinds of DNA polymerases from spleen were not inhibited by bleomycin, but the fourth enzyme, which was induced in the spleen by virus infection, was inhibited by the antibiotic, when poly-d(AT) and poly-dG with dC were used as template.
|
63,972
|
Effect of bleomycin on cell survival and some implications for tumor therapy.
|
Tumor is normally composed of cells growing and non-growing and, therefore, of cells having different responses to exogenous agents. Hence, it is not possible to treat a tumor with an unitary principle. As far as the tumor cell sterilization by bleomycin is concerned, the growing fraction of tumor should be managed by fractional schedule, while plateau phase cells by continuous infusion. Based on the cell sterilization kinetics, further improvement of chemotherapy by bleomycin must be sought. The investigation will duly involve the studies on the nature of resistance induction and PLD repair.
|
63,973
|
Response of mammalian cells to bleomycin-induced potentially lethal and sublethal damage.
|
Both dividing and nondividing cells were able to recover from bleomycin-induced potentially lethal damage, but not from sublethal damage. The recovery from bleomycin-induced potentially lethal damage by nondividing cells was twice as great as that exhibited by dividing cells; and, potentially lethal damage recovery was sufficiently high for cells in both growth states to conceal the true response to sublethal damage. Through the use of integral dose fractions of bleomycin, the recovery from potentially lethal damage can be reduced significantly. These data suggest that closely spaced treatments with fractionated doses of bleomycin may be a more effective means of eradicating tumors containing large nondividing cell populations in vivo.
|
63,976
|
Mental development of phenylketonuric children on or off diet after the age of six.
|
Eleven children with phenylketonuria (PKU) taken off diet after the age of six showed significant decreases in rate of mental development compared with 26 control children children of comparable IQ and with 17 PKU children of comparable IQ who remained on the diet. Changes in rate of mental development were significantly and inversely correlated with plasma phenylalanine levels in treated PKU.
|
63,975
|
Sensorimotor organization in reach and prehension: a development model.
|
A model is presented to depict the organization of the reflex, visual, voluntary motor, and perceptual-cognitive systems in the development of reach and prehension during the first year of life. Five components of hand skills are identified based upon a review of infant scales and observational studies, and the sequential occurrence of behaviors leading to the development of these components is graphically presented. These sequences are juxtaposed to enable the reader to view the temporal relationship of the systems at various stages in the development of reach and prehension in the infant. Items in the models are operationally defined. An explanation is included to clarify the nature and the sequence of events involved in the culmination of mature hand skills. The model should be useful in the identification, analysis, and remediation of deficits in reach and prehension often noted in children with developmental disabilities.
|
63,985
|
Confirmation of the existence of human serum leukaemia-associated antigens (LAA).
|
We have obtained antisera from rabbits which react with serum from several leukaemia patients after absorption with normal human serum. The specificities of these rabbit antisera have been shown to be closely related to those of the original anti-LAA antisera of Viza et al (1970) and Harris et al (1971). Thus, the existence of leukaemia associated (but probably not leukaemia specific) serum antigen in man has been confirmed. One of the animals was immunized with normal amniotic fluid obtained at 15-16 weeks of gestation. Thus, LAA seems to be a normal constituent of amniotic fluid. This suggests that LAA is another onco-fetal component.
|
63,986
|
The immunosuppressive role of alpha-fetoprotein during pregnancy.
|
Cell-mediated and humoral immune responses were assessed in mice at mid-term (day 10) in pregnancy. A significant but selective suppression of the primary in vivo antibody (plaque-forming cell) response to SRBC was observed, with the most pronounced effect being on the gammaA response. Similar results were obtained for secondary in vitro antibody synthesis by antigen-primed spleen cells from pregnant mice, demonstrating the intrinsic nature of the inhibition. Pregnant mouse serum (PMS) was shown to suppress primary in vitro antibody synthesis, and the inhibitory effect was abrogated by the selective removal of alpha-fetoprotein (AFP) using affinity chromatography. Normal mouse serum became similarly suppressive in vitro when purified AFP of fetal origin was added to it in concentrations approximating that found in PMS. Spleen cells from pregnant mice showed a suppressed mitogenic response to phytohemagglutinin, a lowered response to concanavalin. A, and a normal response to lipopolysaccharide. In contrast, the allogeneic response of these animals as measured in the one-way mixed lymphocyte culture was enhanced. PMS suppressed both allogeneic and mitogen-induced lymphocyte transformation by spleen cells from nonpregnant mice, and the effect was eliminated by the selective removal of AFP. These findings indicate an important functional role for AFP in normal embryological development.
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.