Increases in laryngeal cancer in Britain and Australia in relation to alcohol and tobacco consumption trends. The incidence of laryngeal and oesophageal cancers has recently risen in Britain and Australia, particularly in younger people, after many decades of steady decline. In view of accruing evidence that head-and-neck cancers are causally related to alcohol and tobacco consumption, particularly in combination, it seems that the upsurge in consumption of alcohol and cigarettes after the 1939-45 war is now reflected in the increases in these two cancers, particularly in young women. The time-trends in sex-specific mortality from cancers of the larynx and oesophagus throughout this century, in both Britain and Australia, show strong correlations with alcohol consumption. By reference to inter-country differences in consumption trends, to differences in consumption of alcohol and cigarettes, to sex differences in cigarette consumption, to trends in types of alcoholic drink consumed, and to the mortality experienced of successive generations, the evidence that alcohol is causally related to laryngeal cancer is strengthened.


Weight-for-age as an index of risk of death in children. Between April, 1968, and May, 1973, the Department of International Health of Johns Hopkins University studied the effects of the interaction of nutrition and infection in fourteen villages of Punjab, North India. Serial anthropometric measurements (used as index of nutritional status) and vital statistics of almost 3000 children aged 1-36 months showed that, on average, child mortality doubled with each 10% decline below 80% of the Harvard weight median. The relation between season and mortality showed that mortality-rates were highest just before and during the main (wheat) harvest, reflecting the effects of food scarcity, relative child neglect, and climate on child deaths among those already underweight.


Intestinal infection and toxin production by Clostridium botulinum as one cause of sudden infant death syndrome. The spontaneous production of botulinum toxin in the infant gut by ingested Clostridium botulinum organisms is the underlying cause of infant botulism, recognised as an infectious disease only in late 1976. Because of the recognition of the pathophysiology of this disease and because the known potency and action of botulinum toxin can lead to rapid respiratory arrest, it appeared possible that the in-vivo production of botulinum toxin could cause the sudden death of some infants. To test this hypothesis, serum, selected tissues, and bowel contents from 280 dead infants were examined for the presence of C. botulinum toxin and/or organsisms. We found C. botulinum organisms in 10 infants, all of whom died suddenly and unexpectedly. 9 of these deaths were classified by the forensic pathologist as sudden infant death syndrome (S.I.D.S. or crib death). In 2 of these 10 sudden deaths both C. botulinum organisms and botulinum toxin were identified, and from the spleen of 1, C. botulinum organisms were isolated. Faecal specimens from 160 age-matched healthy infants who served as controls in studies of inpatient infant botulism cases were negative for both C. botulinum organisms and toxin, except for one specimen that contained only C. botulinum type A organisms. The 9 S.I.D.S. cases with evidence of C. botulinum infection comprised 4.3% of the 211 S.I.D.S. cases examined over 12 months. These findings suggest that intestinal production of botulinum toxin by C. botulinum is one cause of S.I.D.S. The strikingly similar age-distribution of 62 inpatient infant botulism cases and the 211 S.I.D.S. cases is also consistent with this concept. The possibility that in-vivo production of botulinum toxin may account for a larger proportion of S.I.D.S. cases is discussed.


Infant botulism in England.

Infant botulism in England. A 24-week-old girl presented with an acute illness characterised by constipation at 22 weeks, followed a week later by the sudden onset of generalised weakness, poor feeding, and a weak cry. Laboratory examination of her stools confirmed the clinical diagnosis of infant botulism.


Matching for HLA antigens of A, B, and DR loci in renal transplantation by Eurotransplant. 79 patients and their respective cadaveric kidney donors were typed for HLA-A, HLA-B, and HLA-DR antigens using frozen stored spleen lymphocytes and fresh peripheral-blood lymphocytes. The kidney-graft survival-rate at 3 to 18 months was highest when donor and recipient shared one or two DR antigens and three or four A and B antigens. The graft-survival rate was significantly higher (87 +/- 6%) at 18 months in these patients than in less well matched patients (48 +/- 9%).


Big renin in plasma of healthy subjects on high sodium intake. Normal human plasma contains not only active renin but also an inactive form of renin which, after exposure to low pH, can generate angiotensin I from renin substrate. When healthy volunteers were given first a diet containing 400 mmol sodium and then a diet containing 10 mmol sodium for 4 days the changes in salt intake stimulated large changes in active plasma-renin and smaller changes in inactive renin. Inactive renin comprises a larger fraction of total renin in plasma of salt-loaded healthy subjects than salt depleted subjects. When plasma of healthy men on a high-salt diet was applied to a column of 'Sephadex G-100', renin eluted in two peaks, corresponding to big renin (60 000 daltons) and normal renin of lower molecular weight (40 000 daltons). Active and inactive forms of renin were present in both peaks. Plasma from salt depleted healthy subjects showed a large single peak of renin activity with a maximum at 40 000 daltons. These studies demonstrate that both big and small renin can exist as inactive or active enzyme. Big renin, previously found in certain diseases and in pregnancy, is also present in normal human plasma. These observations suggest a possible physiological role for big renin.


Familial glucocorticoid deficiency with achalasia of the cardia and deficient tear production. Isolated glucocorticoid failure associated with achalasia of the cardia is described in two pairs of siblings in separate families. Defective tear production is also present in three of the patients, and one shows other signs of autonomic dysfunction. Two other families with adrenal insufficiency and achalasia are known. This unusual association probably represents a familial disorder of as yet unknown aetiology.


Dipyridamole and other phosphodiesterase inhibitors act as antithrombotic agents by potentiating endogenous prostacyclin. The antithrombotic effect of dipyridamole is through phosphodiesterase inhibition and depends on stimulation of platelet cyclic A.M.P. by circulating prostacyclin in the bloodstream. Low doses of aspirin selectively inhibit platelet cyclooxygenase and potentiate the antithrombotic effects of dipyridamole and theophylline. High doses of aspirin also prevent prostacyclin formation, thereby abolishing the effects of dipyridamole. Thus, the antithrombotic effectiveness of the combination of aspirin and dipyridamole depends critically on the doses used.


Immunoproliferation and cancer: a common macrophage-derived promoter substance. It is suggested that a common proliferative factor is required for the growth of clones of both antigen-triggered B lymphocytes and carcinogen-triggered epithelial cells, and that the common growth-promoting substance is secreted by macrophages which have originally differentiated in support of the immune response. This macrophage-derived factor seems to be antigenically distinct from granulocyte colony-stimulating factor. Identification of the macrophage-derived clonal proliferative factor could provide new understanding of the proliferation of clones of immunocytes and neoplastic cells.


Heart-rates of surgeons during operations and other clinical activities and their modification by oxprenolol. The heart-rates of surgeons were recorded by ambulatory monitoring methods while they operated and while they conducted surgical outpatient clinics. Heart-rates during operations were also monitored 1 hour after the surgeons had taken an oral dose of 40 mg oxprenolol. During operations the mean heart-rate of 8 surgeons was 121/min with maximum rates in some cases of over 150/min. The tachycardia was abolished by 40 mg of oxprenolol which reduced heart-rates during operations to below those recorded during surgical outpatient clinics. Physical work necessary to reproduce the mean heart-rate whilst operating could not be sustained for more than 10--15 min.


Bone response to termination of oestrogen treatment. Forty-three oophorectomised patients were reviewed 8 years after their initial attendance at a research clinic investigating the aetiology and prevention of postmenopausal osteoporosis. Fifteen patients who had been treated with an oestrogen did not lose a significant amount of bone during the 8 years of therapy. Patients in the placebo-treated control group initially had bone loss of 2.6% per annum, which later fell to an average of 0.75% per annum. Fourteen patients who had been treated with oestrogen for the first 4 years lost no bone, but on withdrawal of oestrogen their bone mineral content fell over the next 4 years at an average rate of 2.5% per annum. 8 years after their initial attendance there was no significant difference between this group and patients who had received placebo for the full 8 years. The result of this study indicates that long-term prevention of bone loss by oestrogens has important medical, social, economic implications.


Impairment of the immune response to vaccination after acute malaria. Children with acute malaria were vaccinated with Salmonella typhi and meningococcal vaccines at varying times after the onset of their illness. The immune response to both vaccines was depressed when they were given on the day of presentation at hospital. Immune responsiveness to S. typhi vaccine was rapidly regained after treatment, but a month after the attack the immune response to meningococcal vaccine was still impaired.


Avoidance of anencephalic and spina bifida births by maternal serum-alphafetoprotein screening. Screening of 11 585 pregnant women between 16 and 20 completed weeks' gestation for raised serum-alphafetoprotein (A.F.P.) levels showed that the birth of 81.4% of babies with open neural-tube defects could be avoided. The screening test was sensitive enough to detect 93% of those affected and serum-A.F.P. levels above the point at which intervention shouldbe considered were found in 1.7% of pregnancies. After 75.2% of false-positives had been excluded by ultrasonography or by a repeat of the serum test, only 0.63% of pregnancies proceeded to amniocentesis, 46.6% of amniocenteses showed raised amniotic A.F.P. levels due to fetal abnormality. Fetal loss by abortion or perinatal death after amniocentesis occurred in 0.034% of pregnancies screeded, 75% being associated with threatened abortion before amniocentesis. There were no terminations of normal pregnancies due to false-positive amniotic A.F.P. results. It is concluded that voluntary maternal serum-A.F.P. screening has a valuable role in antenatal care.


Synthesis of procoagulant antihaemophilic factor in vitro. The cells which produce the procoagulant part of antihaemophilic factor (factor VIII-C) in normal people have remained unknown. Normal blood leucocytes cultured in vitro with phytohaemagglutinin synthesised a procoagulant with the properties of factor VIII-C. The procoagulant was inhibited by human VIII-C inhibitor and itself absorbed human VIII-C inhibitor--properties which are regarded as specific for factor VIII-C. Unexpectedly, cultured leucocytes from haemophiliacs also synthesised the procoagulant in similar amounts. Possible explanations and implications of these findings are briefly considered.


Changes in blood coagulation during total hip replacement. In seventeen patients with osteoarthrosis of the hip undergoing total hip replacement clotting factors II, V, and VIII were measured in blood taken from the operated limb and the general systemic circulation during surgery. Concentrations of these clotting factors were consistently significantly higher in the operated limb than in the rest of the circulation. This result indicates that measures to reduce venostasis in the operated leg during surgery may help to prevent deep-vein thrombosis.


Orcein-positive liver deposits in Indian childhood cirrhosis. A striking, previously unreported pattern of orcein-positive deposits attributed to excess copper-binding protein was found in liver-biopsy specimens from twelve cases of Indian childhood cirrhosis. A comparable picture was found only in biopsy specimens from patients with Wilson's disease. Deposits seen in about 20% of the two hundred and seventy-nine cases in various control groups, which were associated with prolonged cholestasis, were slight in comparison. This finding could have important therapeutic and pathogenic implications.


Nocturnal ulcer pain associated with slow-wave sleep. It is suggested that the early-morning growth-hormone release associated with slow-wave sleep is due to inhibition of somatostatin secretion from the hypothalamus. It is also associated with inhibition of gastrointestinal somatostatin, causing a release of gastrin and insulin. Because the levels of glucocorticoid hormones are concurrently low, the insulin effect is unopposed and increases gut motility through augmented vagal tone. This results in an increased delivery of acid to the duodenum. In duodenal-ulcer patients, whose duodenal buffering capacity is reduced because of a relative deficiency of secretin response, this leads to pain.


Reinterpretation of the haematological effects of anticonvulsant treatment. Blood-counts and folate assays were performed on samples from 102 adults at a residential institution for severe mental impairment. 96 of these patients were receiving anticonvulsant therapy and 6 were not. Only 1 subject had a macrocytic blood-picture, and 5 subjects had hypochromic anaemia. No features of incipient metaloblastic haemopoiesis were identified in the remaining samples. However, serum-folate measured by two assay methods was subnormal in 83% of the samples; red-cell folate was subnormal in 40%. It is concluded that the development of macrocytic anaemia in subjects on long-term anticonvulsants therapy is probably not related to the biochemical process which causes their low assayable folate but reflects inadequate nutrition.


Colonscopy for investigation of unexplained rectal bleeding. 215 colonsocopic examinations were performed on patients with rectal bleeding whose cause had not been determined by barium enema. The probable or definite source of the bleeding was diagnosed in 41% of cases. 13% had a carcinoma, 14% had one or more colonic polyps, 7% had previously unrecognised inflammatory bowel disease. The remainder had various other colonic conditions. The source of bleeding was twice as likely to be found by colonoscopy in patients presenting with frank rectal blood-loss as in those with occult blood. A carcinoma was found twice as often in those patients with diverticular disease as in those without this condition. A lesion was discovered in the majority of patients who had had two or more negative barium enemas. These results emphasise the importance of rectal bleeding as a symptom of colonic abnormality and the value of colonscopy in its investigation in patients where the results of radiology are negative.


Treatment of duodenal ulcer by metiamide. A multicentre trial. In a multicentre double-blind trial 68 patients with endoscopically confirmed duodenal ulceration received metiamide (36 patients) or placebo (32 patients) for four weeks. Healing of duodenal ulcers was significantly increased in patients receiving metiamide (67%) compared with those on placebo (25%). There was also an assoicated significant decrease in daytime pain and antacid consumption in those on metiamide.


Occurrence of other endocrine tumours in primary hyperparathyroidism. In a review of a hundred and nineteen patients with primary hyperparathyroidism an unexpectedly high number (17.5%) were found to have evidence of associated endocrine disease and were deemed to have multiple endocrine adenomatosis (M.E.A.). The clinical pattern of hypercalcaemia in no way distinguished these patients from other hyperparathyroid patients. M.E.A. was most commonly found in patients with several diseased parathyroid glands.


Saralasin bolus test. Rapid screening procedure for renin-mediated hypertension. The angiotensin-blocking agent, saralasin, was given by rapid intravenous (bolus) injection to 21 hypertensive patients. A marked depressor response (average blood-pressure decrease of 30 mm Hg systolic and 20 mm Hg diastolic at 10 minutes after injection) was noted in 13 patients, of whom 11 had renovascular hypertension and 2 had high-renin essential hypertension. No change from prebolus blood-pressure was apparent at 10 minutes in 8 control patients with essential hypertension and normal or low peripheral plasma-renin activity. In all patients, blood-pressure response to saralasin bolus (10 mg) correlated with blood-pressure response to subsequent infusion of saralasin (10 microgram/kg/min). Blood-pressure response to rapid intravenous injection of saralasin--the "saralasin bolus test"--has many characteristics of an ideal screening procedure for renin-mediated hypertension.


Automation of Salmonella typhi phage typing. Two steps in the procedure for bacteriophage typing of Salmonella typhi have been automated. The culture inoculum was applied by flooding the surface of phage agar in a 150x20 mm petri dish and removing the excess liquid with a safety pipettor. This step replaced the older method of manually preparing up to 100 individual areas for inoculation. The number of bacteria per unit area was the same with both methods, so the automated method involved no change in the technique. The second automated step involved use of a bacteriophage applicator which simultaneously dispensed 59 uniform drops of bacteriophages onto the inoculated plate. The automated procedure has reduced personnel time by about 90% with no less in sensitivity or accuracy.


Prenatal diagnosis of homozygous beta-thalassaemia. In two pregnancies at risk for homozygous beta+ and beta0 thalassaemia, fetal blood mixed with maternal blood was obtained by placental aspiration and was purified to over 90% purity by differential agglutination with anti-i antibodies. Study of globulin-chain synthesis showed absence of beta-globulin chain in both fetuses. The diagnosis of homozygous beta-thalassaemia was made and was confirmed after the pregnancies were terminated. Thus, the defect in beta-globulin-chain synthesis in homozygous beta-thalassaemia is expressed in utero, and prenatal diagnosis is possible.


Probenecid and rifampicin serum levels.

Probenecid and rifampicin serum levels. Serum-levels of rifampicin were investigated in patients receiving rifampicin alone or with other antituberculosis drugs. 2 g of probenecid given 30 min before 300 mg of rifampicin did not result in raising serum levels to more than half those achieved with the standard 600 mg dose of rifampicin. Hence probenecid should not be used to reduce rifampicin dosage in antituberculosis therapy.


Down syndrome and thyroid function in adults. Thyroid function has been studied in 11 middle-aged and elderly subjects with proven Down syndrome. Unequivaocal biochemical evidence of hypothyroidism was found in 6, and of thyrotoxicosis in 1. It is concluded that, in contrast to the situation in children with Down syndrome, thyroid dysfunction is exceedingly common in adults with the syndrome.


Increase of contractile proteins in human cancer cells. Human cells from skin and mammary-gland carcinomas show strong immunofluorescent staining with specific antibodies against smooth-muscle actin, myosin heavy meromyosin and light meromyosin, and contain numerous microfilaments as seen by electron microscopy. This increase in the amount of contractile proteins distinguishes cancer cells from the cells of normal tissues.


Polyamines as predictors of success and failure in cancer chemotherapy. Polyamines appear to have clinical utility for monitoring cancer therapy. Investigations on the patterns of urinary excretion of polyamines in patients receiving cancer chemotherapy and studies of the tritiated-thymidine labelling index of tumour cells in a subgroup of these patients form the basis for a hypothesis that spermidine can serve as a marker of tumour-cell kill, whereas putrescine appears to reflect the proliferative behaviour or "growth fraction" of the tumour. Although tests of this hypothesis are necessary to establish the predictive value of polyamines for monitoring cancer therapy, it is clear that polyamines may provide important new information on tumour cytokinetic parameters.


Anesthetic practice and pregnancy. Controlled survey of male anaesthetists in the United Kingdom. 7949 male doctors in the U.K. were surveyed to determine whether there was a relation between operating-theatre work (exposure) and abnormalities in the obstetric history of their marriages. Paternal exposure did not appear to influence the overall abortion-rate or the frequency of major congenital abnormality and involuntary infertility. The frequency of minor congenital abnormality in the children of exposed fathers was 3.09% compared with 2.35% (non-exposed). Maternal exposure was associated with a 15.5% frequency of abortion. Matching of exposed and non-exposed pregnancies with respect to birth order, maternal age, and smoking-habits suggests that the risk of abortion may increase by 158% to 271% with maternal exposure.


Bone disease after jejuno-ileal bypass for obesity. Bone tissue was examined in 21 patients who had undergone jejuno-ileal bypass for obesity between 1971 and 1974. 10 patients had osteomalacia with evidence of secondary hyperparathyroidism. Clinical symptoms and biochemical and radiological investigations were often unreliable in diagnosing bone disease, although plasma-25-hydroxyvitamin-D and plasma-phosphate concentrations were significantly lower and plasma-parathyroid-hormone concentrations were significantly higher in the patients with bone disease. The presence of osteomalacia was unrelated to age, length of time since bypass, or post-bypass weight-loss, and plasma-25-hydroxyvitamin-D levels did not correlate closely with bone histological changes. It is concluded that osteomalacia is common after jejuno-ileal bypass and that factors other than simple vitamin-D deficiency may contribute to its development.


Insulin-reaction test for diagnosis of low renal threshold for glucose in African diabetics. Ten randomly selected Nigerian diabetic patients who were given an intramuscular insulin-reaction test (I.M.I.R.T.) to determine their renal threshold for glucose were found to have a very low mean renal threshold. This finding could be of great significance in the clinical management of Nigerian diabetics in whom relatively high urine-sugar levels may be found despite low blood-glucose levels. It is suggested that the I.M.I.R.T. be routinely carried out, where possible, for more accurate management of the Nigerian diabetic patient.


Acute encephalopathy after initiation of cranial irradiation for meningeal leukaemia. Five patients experienced severe encephalopathy within hours of receiving their initial dose of cranial irradiation for the treatment of central-nervous-system leukaemia. Neurological findings included cranial-nerve palsies, seizures, ataxia, depressed consciousness, increased intracranial pressure, and signs of herniation. Symptoms developed within 3-30 hours of the first radiation treatment of 50-200 rad. Each patient had also received one or more injections of intrathecal chemotherapy before encephalopathy developed. The aetiology of this syndrome is uncertain but may involve transient cerebral oedema and/or an altered blood-brain barrier produced by the combination of intrathecal chemotherapy and cranial irradiation.


Thaw-siphon technique for production of cryoprecipitate concentrate of factor VIII. Plasma, which has been deep-frozen in plastic packs as flat slabs, is thawed in a 3-5 degrees C water-bath, and allowed to siphon continually into an attached satellite pack external to the bath. This thaw-siphon procedure is completed within 55-65 min and the cryoprecipitate, retained in the residual 25 ml of frozen plasma, contains 70-100% of the original plasma factor VIII. Clinical observations in haemophilic patients treated with these cryoprecipitates, have confirmed that the higher in-vitro content of factor VIII is associated with enhanced in-vivo effectiveness.


Inhibition of active-transport sodium-potassium-A.T.P.ase by myeloma protein. Patients with multiple myeloma excrete immunoglobulin light chain (Bence-Jones protein) in the urine. Light chain accumulates in the nephron, and this may result in renal disease, which accounts for the death of between 1 in 4 and 1 in 7 patients with multiple myeloma. Myeloma light chain inhibits transport of paraaminohippurate in the kidney. Evidence is presented here that light chain affects renal transport by inhibiting the active-transport enzyme, ouabain-sensitive Na-K-A.T.P.ase. As a direct consequence, renal A.T.P. content and the maximum rate of gluconeogenesis from lactate are enhanced in the presence of light chain.


Evidence that a hydatid cyst is seldom "as old as the patient". Human hydatid disease caused by the strain of Echinococcus granulosus endemic in Australia and New Zeland has been regarded as a very lonstanding condition, and most cysts diagnosed in adults were believed to have resulted from infection in childhood. A significant drop in the number of new cases among people and 25 and over (P less than 0.05) in two hydatid-control programmes makes it necessary to revise this view. In both Tasmania (P greater than 0.50) and New Zealand (0.50 greater than P greater than 0.10) the incidence was halved without significantly altering the age-distribution. These findings indicate that adults are relatively susceptible and that the latent period between infection and diagnosis in many cases is only a few years.


Lead and morbidity: A dose-response relationship. Many laboratory tests have been recommended for monitoring factory workers exposed to lead. To select the most useful test the best predictor of selected measures of morbidity was sought. 639 lead-exposed workers in several factories were questioned about abdominal ache, constipation, and fatigue and were examined for hand tremot. Packed-cell volume, blood-lead, urinary lead, and delta-aminolaevulinic acid were estimated in 489 workers. About half of the values for the latter three tests fell into the "excessive" or "dangerous" category of lead absorption. Blood-lead was a better predictor of morbidity than any other laboratory test, and further information did not add appreciably to morbidity prediction. The findings suggest that blood-lead measurement is the most meaningful test for monitoring workers exposed to lead. The effect of lead on morbidity does not appear to depend on its action on the porphyrin metabolic pathway.


Treatment of early breast cancer.

Treatment of early breast cancer. The early follow-up of patients treated by simple mastectomy alone or simple mastectomy combined with radical radiotherapy is presented. Both groups were well matched for age, menopausal status, duration of symptoms, size of tumour, and lymph-node involvement. There was no significant difference in survival of patients in the two groups at three years, but local recurrence was significantly more frequent (28%) in the mastectomy-alone patients. Early survival was not adversely affected by radiotherapy.


Is aplastic anaemia due to abnormality of D.N.A.? Lymphocytes from eleven patients with aplastic anaemia were cultured with various agents which interact with D.N.A., and the proliferative responses to phytohaemagglutinin were measured. Lymphocytes from seven of the eleven patients were unduly sensitive to bleomycin, an agent causing strand breaks in D.N.A. The findings suggest that D.N.A. in these seven patients was abnormal, possibly as a result of an abnormality of D.N.A. repair. It is suggested that in aplastic anaemia D.N.A. damage in stem cells may lead to a failure of proliferation.


Post-treatment laparotomy in the management of Hodgkin's disease. Tissues obtained by laparotomy and splenectomy from patients with Hodgkin's disease who had received either supradiaphragmatic irradiation for localised disease or combination chemotherapy for advanced disease were examined histologically. 4 of 19 patients considered to be free of abdominal disease after chemotherapy showed residual active Hodgkin's disease; the spleen was the commonest site showing active disease. 2 patients thought to have intra-abdominal disease showed no histological evidence of active disease in the tissue excised. The finding of residual active abdominal disease in patients considered to be in "clinical" remission indicates that the interpretation of the result of treatment depends on the definition of response. A proportion of "relapses" may, in fact, be patients who never achieve genuine remission of disease, whereas the prognosis for those who do achieve complete remission may be even better than currently accepted, and may even amount to "cure". This study shows that histological changes of lymphoreticular tissue can be defined after treatment and may help in determining more accurately the need for further therapy.


Sperm basic proteins in cervical carcinogenesis: Correlation with socioeconomic class. Two types of basic protein, a histone and a protamine, were separated from single ejaculates of human sperm and a ratio between their contents in a given number of sperm established. The ratio varied widely in different males and correlated with ranking by social class: the lower the social class, the greater the proportion of protamine. Statistically similar correlations link social class with the incidence of venereal disease and the incidence of in-situ carcinoma of the cervix, both of which are epidemiological variables in squamous cervical cancer. The basic proteins of the sperm head, especially the protamines, may thus also have a role in the aetiology of squamous cervical cancer.


Leucocyte adherence inhibition test in arthritis. Peripheral leucocytes from healthy blood-donors were preincubated in polyarthritic serum or normal serum and their adherence to glass tubes in the presence of synovial extract of control extract was measured. Serum from patients with inflammatory polyarthritis significantly reduced the proportion of leucocytes which adhered in the presence of synovial extract, but not control extract. Serum from patients with polyarthritis with visceral manifestations, patients with degenerative or metabolic polyarthritis or rheumatic fever, and controls did not have this effect. The leucocyte sensitising activity was eluted in the IgG fraction of serum, and could be absorbed by both synovial extract and IgG. It is thus probably IgG rheumatoid factor. In vivo, armed leucocytes in polyarthritic patients may bind to synovial tissue initiating or perpetuating the articular inflammatory process.


Effects of therapy on plasma-high-density-lipoprotein-cholesterol concentration in diabetes mellitus. In 122 diabetic patients there was a signnificant inverse correlation between plasma-high-density-lipoprotein (H.D.L.)-Cholesterol concentrations and glycosylated haemoglobin concentrations. In an insulin-treated subgroup improvement in diabetic control, confirmed by a decrease in glycosylated haemoglobin concentrations, was accompanied by a significant rise in plasma-H.D.L.-cholesterol concentration. This result suggests that improved diabetic control may diminish the risk of premature ischaemic heart-disease. When three groups of patients on different treatments were matched for age, sex, weight, and diabetic control, diabetic patients receiving sulphonylureas had significantly lower plasma-H.D.L.-cholesterol concentrations than those receiving insulin or on diet alone, or non-diabetic controls. This association suggests that sulphonyl-urea administration may constitute a positive risk factor for ischaemic heart-disease in diabetic patients.


Immunogenicity and antigenicity of soluble cross-linked enzyme/albumin polymers: Advantages for enzyme therapy. Soluble cross-linked polymers of hog-liver uricase and an excess of either rabbit or dog albumin were injected repeatedly into rabbits in order to determine their antigenicity and immunogenicity. Whereas the enzyme in its free form induces antibody production, homologous albumin polymerised with the enzyme renders the complex non-immunogenic and non-antigenic. Dog-albumin/uricase polymers injected into rabbits induce antibody formation against the dog albumin but not against the uricase. The results suggest an important advantage of these soluble enzyme polymers in enzyme-replacement therapy.


Combined therapy with salbutamol and beclomethasone inhalers in chronic asthma. A double-blind cross-over trial was carried out to compare the effect of identical placebo with that of salbutamol inhalers used 30 min before inhalation of 100 microgram of beclomethasone dipropionate (B.D.P.) in 18 chronic asthmatics over two consecutive 4-week periods. The salbutamol and B.D.P. combination resulted in a significant improvement in the peak expiratory flow-rate and F.E.V.1, significantly less use of the rescue inhaler, and better control.


Immune complexes in ovarian cancer.

Immune complexes in ovarian cancer. Immune complexes have been assayed in ovarian cancer with a polyethylene-glycol (P.E.G.) precipitation assay and a Clq solid-phase assay. Significantly higher levels of immune complexes were detected in patients in relapse compared with those in remission. Remission values were within the range obtained for a control group. Evidence was produced that immune-complex levels rise before the clinical detection of relapse, and it is suggested that the P.E.G. assay could be a useful marker of disease progress.


Plasma-secretin in management of cimetidine therapy for Zollinger-Ellison syndrome. A patient with Zollinger-Ellison syndrome was treated by an H2-receptor blocking drug (cimetidine). Treatment was successfully monitored by plasma-secretin levels which were linearly related to the acid load delivered to the duodenum.


Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? When mice are infected with either of several species of Plasmodium or Babesia the amount of Escherichia coli lipopolysaccharide (L.P.S.) required to kill them is decreased several hundred fold. The higher their parasitaemia the greater their susceptibility. There is indirect evidence that more L.P.S. than usual is present during infection with these parasites. In a very susceptible host this may be sufficient to produce endotoxin shock. Non-antibody mediators able to kill rapidly dividing cells, which are released during endotoxin shock, may then control the parasitaemia of acute primary attacks. This may explain why agents such as B.C.G., which produce responsiveness to abnormally low concentrations of L.P.S., protect against infection with certain of these parasities. It may also explain why host species naturally resistance to L.P.S. become ill only at high parasite concentrations, and why others with a naturally high susceptibility to L.P.S. become ill when infected with relatively few parasites. In the individual host convalescence from certain bacterial infections or concomitant infection with L.P.S.-producing organisms may vary the parasitaemia required to produce illness.


Post-traumatic skull radiographs. Time for a reappraisal. 504 patients who had skull radiographs for head injury are included in this study. Only 9 (1.9%) had demonstrable fractures. 129 (25%) of the patients reviewed were admitted to hospital. 93 of these were admitted for up to 24 hours, and 36 for a longer period, usually for conditions unrelated to the head trauma. All but 1 of the patients with a demonstrable skull fracture were admitted to hospital, and the radiographic findings initiated active medical intervention in 2 of these cases. There was no correlation between radiographic findings and the need for hospital admission, and little correlation between radiographic findings and the presenting signs and symptoms. It is, therefore, suggested that the indications for skull radiography in the management of head injuries require reappraisal.


Drug-induced gastrointestinal bleeding. Report from the Boston Collaborative Drug Surveillance Program, Boston University Medical Center. Rates of drug-induced gastrointestinal bleeding were estimated from data on 16 646 consecutively monitored medical inpatients who had no known predisposing illness. Heparin, warfarin, ethacrynic acid, steroids, and aspirin-containing drugs were associated with gastrointestinal bleeding and were estimated to account for about two-thirds of such bleeds. Major gastrointestinal bleeding, defined as bleeding severe enough to require transfusion, occurred in only 57 patients (0.3%).


Cyanide exposure in fires.

Cyanide exposure in fires. The toxic hazard from cyanide produced in fires was assessed in casualties and in firemen exposed to the fire atmosphere. The levels of cyanide and its principal metabolite, thiocyanate, were measured in blood samples from fireman, non-fetal and fatal casualties, and from controls. Although firemen did not differ significantly from controls, casualities showed significant elevation of blood-cyanide, and in a small proportion of fatalities blood-cyanide reached toxic levels.


Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Unlike arachidonic acid (eicosatetraenoic acid, C20:4omega-6, A.A.), eicosapentaenoic acid (C20:5omega-3, E.P.A.) does not induce platelet aggregation in human platelet-rich plasma (P.R.P.), probably because of the formation of thromboxane A3 (T.X.A3) which does not have platelet aggregating properties. Moreover, E.P.A., like A.A., can be utilised by the vessel wall to make an anti-aggregating substance, probably a delta17-prostacyclin (P.G.I3). This finding suggests that, in vivo, high levels of E.P.A. and low levels of A.A. could lead to an antithrombotic state in which an active P.G.I3 and a non-active T.X.A3 are formed. Eskimos have high levels of E.P.A. and low levels of A.A. and they also have a low incidence of myocardial infarction and a tendency to bleed. It is possible that dietary enrichment with E.P.A. will protect against thrombosis.


beta-Endorphin in human cerebrospinal fluid. beta-endorphin is a brain peptide with potent morphine-like activity structurally related to the anterior pituitary hormone beta-lipotrophin (beta-L.P.H.). We have developed a radioimmunoassay for human beta-endorphin in plasma and cerebrospinal fluid (C.S.F.). Since the antiserum also reacts with beta-L.P.H., beta-endorphin was distinguished by using a second antiserum which measures beta-L.P.H. alone. With these two immunoassay systems and gel chromatography, we found beta-endorphin in all 20 C.S.F. samples tested at a concentration always higher than, but with no other relationship to, that in plasma. beta-endorphin was found in C.S.F. of patients who had hypopituitarism and undetectable plasma-beta-endorphin, suggesting that it is synthesized in the brain rather in the pituitary.


1974 outbreak of Legionnaires' Disease diagnosed in 1977. Clinical and epidemiological features. An illness characterized by high fever and pneumonia struck 2.9% of a group of the Independent Order of Odd Fellows attending a convention held in Philadelphia, in September, 1974. The convention headquarters was the hotel where the American Legion met in July, 1976. The epidemiological, clinical, and laboratory characteristics of the illness were nearly identical to those of the disease in American legionnaires in 1976. Illness was significantly associated with attendance at one convention activity held on Monday morning, Sept. 16, 1974, in the grand ballroom of the hotel. A serological survey in February and March, 1977, showed that people who had attended the convention and became ill were more likely to have raised indirect fluorescent antibody titres than persons who had attended and remained well. The illness seen in Odd Fellows members in September, 1974, was caused by the legionnaire's disease organism.


Sex and prognosis in childhood acute lymphoblastic leukaemia. Prognostic factors at diagnosis were examined in 67 children who presented with acute lymphoblastic leukaemia in 1970-76 and received modern treatment, incorporating prophylactic cranial irradiation and maintenance chemotherapy for at least 2 years. The effects of age and white blood-cell (W.B.C.) count were evident as in many previously reported studies but comparison of lifetables showed that the duration of haematological remission and complete remission was significantly shorter for boys than for girls. The difference in their survival was not significant. The risk of haematological relapse for boys and significantly greater even when relapses associated with the central nervous system or testicular relapse were excluded. The sex differences were not adequately explained by differences in initial W.B.C. count or in age.


Plasma-prostaglandins in pre-term neonates before and after treatment for patient ductus arteriosus. 9 pre-term babies with patent ductus arteriosus (P.D.A.) and cardiac failure were found to have significantly higher plasma-levels of three prostaglandins (P.G.E, P.G.F, and P.G.FM) than a group of normal pre-term infants of the same age. There was no difference in the plasma-prostaglandin levels before and after surgery in the 5 infants who underwent ligation of the ductus, suggesting that the high P.G. levels are not the result of a patent ductus, but that P.G.S may have a role in the pathogenesis of P.D.A. 3 infants who were treated by indomethacin (a P.G. synthetase inhibitor) showed a sharp initial drop in plasma-levels of the three P.G.S, but levels of P.G.F and P.G.FM had risen either during or within 48 h of completion of the course of indomethacin. These results may explain why high failure-rates have been reported for treatment of P.D.A. by indomethacin.


Cilia and sperm tail abnormalities in Polynesian bronchiectatics. Sperm tails and bronchial cilia from Polynesians with bronchiectasis were examined in the electron microscope. The outer doublet tubules of the axonemal skeleton in these organelles either lacked dynein arms or had only partial arms. Various other cilial abnormalities were common. The sperm were immotile and pulmonary mucociliary clearance was reduced or absent.


Medical screening of old people accepted for residential care. Medical screening of 100 old people at the time of their acceptance for admission to residential (part 3) care revealed a great deal of previously unreported yet treatable illness. As a result of screening, alternative care was thought more appropriate in 32 cases--hospital admission in 16, sheltered housing in 4, and remaining at home in 12. It is therefore suggested that the time of translocation of an old person from independent to institutional living is a time when medical screening is particularly appropriate.


Nitrogen-oxygen saturation therapy in serious cases of compressed-air decompression sickness. Decompression sickness and arterial air embolism which follow exposure to raised environmental pressures of compressed air are usually adequately treated by accepted recompression procedures of relatively short durations. With serious cases, however, conventional treatment may not allow sufficient time at depth for the complete resolution of manifestations because of the need to avoid pulmonary oxygen toxicity which is associated with a prolonged period of breathing compressed air. Treatment by nitrogen-oxygen saturation at a pressure equivalent of 30 m (100 ft) sea water is proposed. Based upon the success of three refractory cases treated by this procedure, recommendation are made for the conversion of standard compressed-air chambers into an emergency saturation mode for therapy.


Long-term follow-up of preterm infants in breech presentation delivered by caesarean section. A prospective study. All forty-two breech infants delivered by caesarean section before the 37th gestational week since Jan. 1, 1975, were followed up prospectively. Outcome in this group was compared with that for all forty-eight breech infants delivered vaginally in 1971-74, before the introduction of routine caesarean section. Delivery by caesarean section significantly reduced the frequency of severe prolonged asphyxia, and neonatal mortality was reduced from 14.6% to 4.8%. At 12 months of age 24% of those delivered vaginally had developmental or neurological abnormalities compared with 2.5% of those delivered by caesarean section.


Factors influencing lactation performance in rural Gambian mothers. Breast-milk consumption has been measured in a rural African community in which breast-feeding on demand is universally practised until the baby is 18 mos old. The mother's long-term capacity for breast-milk production is determined by the end of the second month of lactation, yield being closely correlated with the infant's birth-weight. Other factors significantly influencing output were parity, month of lactation, baby's weight-for-age, season, and maternal diet. Daily milk consumption was limited primarily by the amount delivered per feed, not the frequency of feeding.


Role of Escherichia coli colonisation factor antigen in acute diarrhoea. The role of colonisation factor antigen (C.F.A.) in diarrhoea was studied in volunteers who ingested either E. coli H-10407, which possessed C.F.A., or H-10407-P, which lacked C.F.A. In the first study the dose given was 10(6) C.F.A.+ or C.F.A.- E. coli; in the second study the dose was 10(8) of the same organisms. Diarrhoea, with or without other symptoms, occurred only in those who ingested 10(8) C.F.A.+ E. coli. Those volunteers taking the C.F.A.- strain shed the test organism in the stool for only 2 or 3 days whereas those ingesting the C.F.A+ strain shed the organism until the end of the study (7 days). Antibody responses in those ingesting the C.F.A.+ strain were: anti-C.F.A., 7 of 12 volunteers; antitoxin, 6 of 13; and anti-O78 somatic antigen, 11 of 13. No volunteer ingesting the C.F.A. organism seroconverted to any of the antigens. The study showed the importance of C.F.A. in the pathogenesis of human disease due to toxigenic E. coli.


Variations in chemical mediators of hypersensitivity in the sputum of chronic bronchitics: correlation with peak expiratory flow. Histamine, slow reacting substance of anaphylaxis (S.R.S.-A), IgE, eosinophils, and an eosinophil-associated enzyme, arylsulphatase IIB, were measured in sputum from 11 chronic bronchitics at weekly intervals for 6 weeks. The agents were detected in all patients at some time and in the majority at all times throughout the study period although their concentrations varied. The variations in histamine, S.R.S.-A and IgE gave a highly significant negative correlation with the peak expiratory flow-rate, suggesting that chemical mediators of hypersensitivity may play some role in the pathogenesis of airways obstruction in this disease. Sputum eosinophilia correlated with the arylsulphatase IIB concentration but not with the peak expiratory flow-rate, IgE, histamine, or S.R.S.-A, a finding consistent with the view that eosinophils accumulate at the site of type I reactions after the peak of mediator release.


Crohn's disease in a husband and wife.

Crohn's disease in a husband and wife. The case-histories of a husband and wife in whom Crohn's disease developed after more than 30 years of marriage are described.


Possible initiation of viral encephalomyelitis in dogs by migrating lymphocytes infected with distemper virus. The principal pathways by which viruses spread to the central nervous system (C.N.S.) are considered to be direct invasion along peripheral nerves or the haematogenous route. The latter is thought to involve passive transfer or active replication of virus in C.N.S. endothelial cells. In this study histological evidence of mild perivascular encephalomyelitis was found 8-10 days after infection of dogs with canine distemper virus (C.D.V.). C.D.V. antigen and viral nucleocapsids were detectable in the mononuclear cells infiltrating nervous tissue and C.D.V. was isolated from lymphoid tissue and buffy-coat cells. C.N.S. infection may thus be initiated by migrating virus-infected lymphocytes and this pathway may operate in other viral disorders of the C.N.S.


Haemophilus meningitis in Portsmouth.

Haemophilus meningitis in Portsmouth. The clinical features and follow-up data of all twenty-five children admitted to a Portsmouth hospital from Jan. 1, 1972, to July 1, 1975, with haemophilus meningitis were reviewed. Two children died of meningitis and one of other causes. Four have residual damage--two severe, one definite, and one possible. Outcome tended to be worse in cases with the following features: age less than 9 months at the time of illness, difficult diagnosis, antibiotic treatment before admission, combined treatment with chloramphenicol and ampicillin, and difficulties at home. The continuing high morbidity indicates that children with this disease need careful follow-up.


Zinc content of intravenous solutions.

Zinc content of intravenous solutions. The zinc, copper, and selenium content of commonly used intravenous solutions, aminoacid solutions, and fresh-frozen plasma was determined by atomic absorption spectrometry and fluorimetry. Very small amounts of copper and variable, but substantial, amounts zinc were present in all solutions tested. Zinc contamination could have come from the rubber stoppers for the glass bottles. Selenium could not be detected in any of the solutions. Fresh-frozen plasma contained high levels of zinc and physiological amounts of copper and selenium.


Thyroid function in patients undergoing maintenance hemodialysis: unexplained low serum thyroxine concentration. Thyroid function was studied in 55 patients undergoing maintenance hemodialysis who were all judged to be clinically euthyroid. The dialysis patients, in comparison to normal control subjects, had significantly lower mean values for serum T4 (4.0 +/- 1.4 [SD] microgram/dl versus 7.9 +/- 1.5 microgram/dl, p less than 0.001), T3 (118 +/- 31 ng/dl versus 147 +/- 28 ng/dl, p less than 0.001), free T4 measured by equilibrium dialysis (1.22 +/- 0.38 ng/dl versus 2.15 +/- 0.67 ng/dl, p less than 0.001), free T3, free T4 index, and free T3 index. Serum TBG, measured by radioimmunoassay, was similar to that of the controls and serum TSH, 2.2 +/- 1.3 micromicron/ml, was also similar to that of control values, 2.0 +/- 1.1 micromicron/ml. The serum PBI did not change during the dialysis procedure, but serum inorganic iodine fell slightly from 2.1 +/- 1.1 microgram/dl before dialysis to 1.2 +/- 0.6 microgram/dl after dialysis (p less than 0.05). The marked reduction in serum total T4 and free T4 concentrations and the moderate reduction in serum total T3 and free T3 levels in apparently euthyroid patients undergoing hemodialysis has not been explained. The normal serum TSH levels in the face of these low concentrations of thyroid hormone suggests an abnormality in the control of TSH secretion in these patients.


[General amyloidosis associated with Hashimoto-hypothyroidism (author's transl)]. We are reporting a case of perireticular as well as pericollageneous amyloidosis developing in a 65 year old patient with Hashimoto-hypothyroidism. The data presented suggest the presence of two primary, not interrelated disorders. Amyloid deposits were found in liver, rectum and bone marrow biopsies.


A kinetically designed chemotherapeutic regimen for advanced refractory lymphoma patients. Three patients with Hodgkin disease, eight with non-Hodgkin lymphoma, and one with chronic lymphocytic leukemia refractory to conventional combination chemotherapy were treated for remission induction with a new kinetically designed four-drug combination consisting of bleomycin, vincristine, adriamycin, and prednisone and given the acronym "BOAP." Eight patients had prior radiotherapy, included two who had total nodal irradiation. Eight patients (all three with Hodgkin disease and five of eight with non-Hodgkin lymphoma) achieved complete remission (73% of the lymphoma patients). An additional two patients with non-Hodgkin lymphoma sustained partial remissions, for an overall response rate of 91%. Toxicity caused the interruption of therapy in three patients and an additional patient might have sustained a drug-related death. This study compares favorably with other studies investigating primary or secondary combination chemotherapy of advanced lymphomas.


[Immunochemical comparison of tryptophanyl-tRNA-synthetases]. A fraction of immunoglobulins was isolated from the sera of rabbit immunised by a homogeneous beef pancreas tryptophanyl-tRNA-synthetase (TRSase). The IgG fraction was shown to inhibit the enzymatic activity during aminoacylation of yeast tRNATrp and tryptophan activation. By using the radioimmunoadsorption technique, the interaction of IgG was tested with TRSaes from beef pancreas and identical enzymes from other sources (contained in the total preparation). Beef liver TRSase efficiently inhibited the radioimmunoadsorption reaction of beef pancrease 125J-TRSase that suggests a strong similarity or even identity of the enzymes. When the purified antibodies to beef pancreas TRSase were isolated common antigen determinants were revealed for TRSase from beef pancreas, liver of chick, pig and rat. Enzymatic activity of TRSase from liver of beef, pig and chick was shown to be inhibited by antibodies to beef pancreas. TRSase whereas the enzymes from rat liver and yeast did not change their activity in the presence of these antibodies. Therefore, for several TRAases common antigen determinants have been revealed that suggest the presence of common structural elements in these enzymes; antibody binding inhibits the activity of some TRSases and does not affect that of others.


[Relative positions of stainable portions of DNA in deoxyribonucleoprotein fibrils]. The effect of acridine orange (AO) concentration on fluorescence polarization of DNA, DNP100 and DNP250 solutions (100 A and 249 A thick DNP fibers, respectively) was studied. It was shown that fluorescence depolarization by an excitation energy migration mechanisms is 3.5 times more efficient for DNP250 than for DNP100. Higher efficiency of energy migration may be explained by a tighter packing of stained DNA regions inside the 250 A fiber because both DNP100 and DNP250 have equal numbers of AO binding sites. The calculated average number of packed DNA strands in DNP250 is 3, the average angle between them is 26.5 degrees. A model of the 250 A DNP fiber is proposed. In this model nucleosomes form a tight 250 A coil with a 430 A pitch, internucleosomal DNA strands are oriented approximately along the fiber axis.


A controlled trial of immunotherapy in insect hypersensitivity. Insect hypersensitivity is currently treated by immunization using whole-body extracts. We compared this regimen with immunotherapy using insect venoms or placebo in groups of 20 patients matched for history and sensitivity, as judged by venom skin test, histamine release and IgE antibody to venom. After six to 10 weeks of immunization, systemic reactions to stings occurred in seven of 12, seven of 11, and one of 18 patients treated with placebo, whole-body extract, and venom, respectively. Placebo and whole-body extract gave similar results and were significantly less effective than venom immunotherapy (P less than 0.01). The 14 patients with failure of treatment with whole-body extract and placebo were subsequently provided with venom immunotherapy; one reacted to a subsequent sting. We conclude that venom immunotherapy is clinically superior to therapy on whole-body extract or placebo.


A method for classification of 5' termini of retroviruses. A new method for the classification of retroviruses is presented. The scheme is based on the length and sequence of a DNA transcript of the 5' end of the genome. The method can be used to detect similarities between distantly related viruses as well as to discriminate between very closely related viruses. The method is applied to viruses isolated from mice, baboons, gibbons, a woolly monkey and chickens.


[Limits and possibilities of neoplasm immunotherapy]. Immunological treatment of malignant human tumors has so far met with little success. Based on methods and insights obtained by investigation of corresponding animal models, this article attempts to elucidate the reasons for this failure and to suggest ways and means to improve immunotherapeutic approaches to human neoplasms.


[The gastric mucosa barrier and gastropathy]. In addition to a layer of mucus, the gastric mucosa barrier is mainly formed of a tight junction consisting of the surface membranes of epithelial cells. It is this that mainly impedes the flowback of H+ ions. Buffers conveyed by the blood neutralise the small numbers of ions that do flow back, even under physiological conditions. Damage to the barrier results in a considerable backflow of ions that enhance acid secretion and release of histamine and other vasoactive substances, so that further mucosal lesions occur. Such damage may be of exogenous or endogenous origin. Alcohol and acetylsalicylic acid are two examples. The latter is undissociated and hence liposoluble in the highly milieu of the stomach and can easily enter the cells and damage them. Severe hypovolaemia, stress and sepsis are instances of endogenous sources of damage. In the final analysis, the damage caused by sepsis is linked to cell anoxia.


Delayed recurrence and chemotherapy of a granulosa cell tumor. A case of proved delayed recurrence of a granulosa cell tumor 18 years after initial diagnosis is presented. L-Phenylalanine mustard was given after radiation was refused for the unresectable mass. A prolonged complete remission was produced. The present status of palliative therapy of recurrent granulosa cell tumor is discussed with a request for the reporting of experiences with more patients treated with chemotherapy.


Negative staining of a non-haemadsorbing strain of African swine fever virus. Since the application of negative staining, preceded by fixation, prevents the disruption and distortion of the capsid of the African swine fever virus, improved contrast and evaluation of the appearance and size of virus particles in the electron microscope is possible and, in addition, the icosahedral shape of the virus is demonstrable. The mature virus particle contains at least 2 capsid layers and an outer envelope.


Lymphoblastic conversion in chronic myelogenous leukemia. A child presented with "acute leukemia" in which the blast cells resembled lymphoblasts and had negative cytochemical staining (PAS, Sudan black, and myeloperoxidase). Remission was induced and typical adult-type chronic myelogenous leukemia (CML) followed. Cytogenetic studies initially and during remission and subsequent "acute leukemia" relapses revealed the presence of the Philadelphia chromosome abnormality. Terminal transferase assay performed on peripheral blood blast cells was markedly elevated and soft agar culture growth parameters were typical of acute lymphoblastic leukemia T and B cell marker studies revealed no markers. This case report with supportive laboratory studies suggests that a cell line with lymphoid characteristics may predominate during acute leukemic transformation. This type of subclassification of leukemia may be of importance in therapeutic planning.


Effect of parenteral fat emulsion on the pulmonary and reticuloendothelial systems in the newborn infant. Analysis of phospholipids (PL), cholesterol esters, triglycerides (TG), and free fatty acids (FFA) was performed on plasma and RBCs in two sick low-birth-weight infants who received total parenteral nutrition including Intralipid for the first 9 and 12 weeks of life, respectively. There was an increase in the total concentration of the plasma IG and FFA in the infants receiving Intralipid as compared with controls. These elevated lipid levels were not detected by visual inspection of the plasma. When compared with control infants, higher levels of linoleic acid were found in the plasma and RBCs of infants receiving Intralipid while plasma PL contained less arachidonate. Histological examination of the lung in both infants who received Intralipid revealed numerous globules of sudanophilic material in alveolar macrophages and capillaries. There is a possibility that prolonged administration of Intralipid may be associated with altered pulmonary and reticuloendothelial system function.


[Relationship between digital necrosis of the upper limbs and malignant conditions (author's transl)]. The authors report six new cases of necrosis of the fingers occurring during the course of a malignant condition. None of the patient was suffering from any other disease which could explain the digital necrosis. They discuss the mechanism of the relationship between the two conditions : blood hyperviscosity, thrombocytosis, polycythaemia, cryoglobulin and the production of immune complexes. The particular role of bleomycin is mentioned. The possibility of a true paraneoplastic syndrome is suggested.


[The influence of the galenic form of 131I administration on the results of radioiodine tests--comparison of 131I in capsules and in solutions (author's transl)]. A comparative study of thyroid uptake and PB131I in two groups of 20 euthyroid persons each was performed. In one group 131I was administered in the form of capsules and in the other as a solution. The application of 131I in capsule form showed no significant decrease of thyroid uptake at 2, 24 and 48 hr but a significant diminishment of PB131I 48 hr after capsule ingestion (p less than 0,05). In 3 patients the scintiscans of the abdomen 24 hr after administration of three 131I capsules (90 muCi) revealed no circumscribed areas of activity. Because the iodine metabolism is dependent upon the kind of carrier, we conclude that for thyroid uptake measurements and the following 131I therapy the same 131I preparation should be used.


"Nonspecific" cholinesterase and acetylcholinesterase in rat tissues: molecular forms, structural and catalytic properties, and significance of the two enzyme systems. "Nonspecific" cholinesterase (acylcholine acylhydrolase; EC 3.1.1.8) from various rat tissues has been found to exist in several stable molecular forms that appear as exact counterparts of molecular forms of acetylcholinesterase (acetylcholine hydrolase; EC 3.1.1.7). The sedimentation pattern of cholinesterase was similar to that of acetylcholinesterase with a small but significant shift between the sedimentation coefficients of the corresponding forms. Extraction yields in different media also demonstrated a close parallelism between the two enzyme systems. Other properties, such as thermal stability and catalytic characteristics, indicated both differences and similarities. In spite of the structural resemblance implied by their physicochemical properties, cholinesterase did not crossreact with antibodies against acetylcholinesterase. The nature of the relationships revealed by these studies and their bearing on the physiological significance of cholinesterases are discussed.


Adult murine T cells activated in vitro by alpha-fetoprotein and naturally occurring T cells in newborn mice: identity in function and cell surface differentiation antigens. Murine alpha-fetoprotein (alphaFP) has been shown to suppress T cell-dependent antibody responses in vitro but not T cell-independent responses. Our earlier preliminary findings indicated that such inhibitory effects are mediated via activated T cells. In this study, using alphaFP as the inducing agent, we have analyzed cells generated in vitro from adult spleen cells with regard to function and surface markers and compared the cells to the naturally occurring splenic T cells of newborn mice, in which there are high intrinsic concentrations of alphaFP. Both types of T lymphocytes were found to effectively inhibit T cell-dependent antibody responses in vitro but not T cell-independent responses. Moreover, both groups of T cells were found to express the identical differentiation antigen phenotype,Ly 1 + 2-. Thus alphaFP-induced inhibitory T cells from adults could be shown to have the same functional properties and Ly phenotype as splenic T lymphocytes from newborn mice. These findings support the concept that alphaFP might function as an important immunoregulatory agent in vivo during ontogenetic development.


A new approach to the structural determination of glycoproteins and polysaccharides: anhydrous HF solvolysis. From experiments with glycoproteins containing the glycopeptide linkages, arabinose-O-hydroxyproline and galactose-O-serine (plant cell wall glycopeptides), N-acetylgalactosamine-O-serine/threonine (pig submaxillary mucin), and N-acetyl-glucosamine-N-asparagine (fetuin), it is apparent that anhydrous liquid HF, a reagent commonly used by snythetic peptide chemists for the complete removal of protecting groups from synthetic peptides, cleaves the O-glycosidic linkages of neutral sugars in 1 hr at 0 degrees  C, and the O-glycosidic linkages of amino sugars in 3 hr at 23 degrees C. The N-glycosidic linkage of N-acetylglucosamine to asparagine is not cleaved under any conditions that have been tested. Sodium dodecyl sulfate gel electrophoresis of bovine serum albumin treated in HF does not show any degradation of peptide bonds. Some relatively stable enzymes (lysozyme and RNase) have been shown by others to retain most of their enzymic activity after short treatment (1 hr at 0 degrees C) in HF. With the specificity of HF at 0 degrees C for neutral sugars it should be possible to generate di- or trisaccharides in high yield from polysaccharides containing both neutral and amino sugars with neutral sugars as the reducing termini.


Radiotherapy of carcinomas of the extrahepatic biliary system. Carcinomas of the gallbladder and extrahepatic bile ducts carry a dismal prognosis. Due to the proximity of a number of vital structures and their early invasion, these tumors are rarely resectable. Long-term survival or cure is an exception. Results of treatment in 11 patients are reported. In 4 patients, radiotherapy was given as an adjuvant to surgery; in 5 patients the aim was palliation, while 2 patients received potentially curative doses of radiation. Good palliation has been achieved. Long-term, disease-free survival has been observed in some radically treated patients. The results suggest that radiotherapy may contribute to cure not only when used as a surgical adjuvant but also as the sole treatment modality in unresectable but still localized carcinomas of the bile ducts.


Effect of topical prostaglandins on nasal patency in man. The effect of prostaglandin E1 and 17 phenyl trinor PGE2 on nasal patency has been studied in healthy volunteers and in patients with vasomotor and allergic rhinitis. Both drugs applied topically increased nasal patency. The effect of a single dose of either compound lasted for several hours. Prostaglandin E1 produced nasal irritation and throbbing, lacrimation, headache and sore throat. Except for occasional brief nasal irritation, these side effects were not encountered with 17 phenyl trinor PGE2.


[Structure of the use of symbols in schizophrenic language]. The structure of the use of symbols in schizophrenia is examined, based on a recorded text spoken by a 35-year-old schizophrenic teacher (female). At specific points in this text, symbolic usage can be determined. The structural analysis illustrates a schizophrenic alteration which exists in each case through the substitution of a secondary meaning for a primary one. This structure is present in all cases. (In addition, the text also contains a symbol stemming from folk tradition.) This structure is identical with the structure of linguistic alteration in schizophrenics as well as that of the structure of schizophrenic delusions. This present study concentrates on the formal analysis of the use of symbols and does not present a close analysis of the content.


Starch degradation during germination of Civer arietinum L. seeds. The variations in starch and soluble sugar content, in phosphorylase and amylase activities in cotyledons of germinating seeds of Cicer arietinum L. are determined. Results from various experiments prove that the alpha-amylases are chiefly responsible for amylase activity. Phosphorylase plays an important rôle during the first two days of germination, but it is relegated to a secondary position as the amylase activity increases. Disc electrophoresis on polyacrylamide gel shows the existence of a phosphorylase throughout germination, and detects two alpha-amylases after 48 and 96 h germination respectively. The increase in alpha-amylase activity during germination is due to de novo synthesis of the two isoenzymes, since both are inhibited by cycloheximide and actinomyces D. This de novo synthesis depends on some embryo produced factor, unreplaceable either by giberellic acid or by kinetin.


Urinary excretion of albumin beta2-microglobulin and free light chains during lithium treatment. Albumin, beta2-microglobulin and free light chains were determined in urine in nine manic-depressive patients before and at intervals during three months of lithium treatment (longitudinal study). The same determinations were carried out in twenty-seven manic-depressive patients who had been treated with lithium for 3 months to 20 years and also in a control group (transversal study). There were no statistically significant changes in urinary excretions of albumin, beta2-microglobulin and free light chains during the longitudinal study. In one patient albumin excretion gradually increased during the study and remained elevated on reexamination 1 year later. No significant differences were found between the lithium treated patients and control subjects in the transversal study in either albumin, beta2-microglobulin or free light chain excretion. It is not clear whether the increased and sustained albumin excretion in one of the patients was due to lithium or was conincidental. The study shows that in most patients lithium treatment does not affect renal protein excretion.


Urinary excretion of beta2-microglobulin in renal stone patients under normal conditions and during acidosis and alkalosis. The urinary excretion of beta2-microglobulin was studied under normal conditions and during acidosis and alkalosis in 65 patients with renal stones. Eleven patients were studied under two of these conditions. Four out of 51 patients examined under normal conditions had an increased excretion of beta2-microglobulin in their urine. Four out of five patients with distal acidification defects were found to have an increased excretion of beta2-microglobulin during induced acidosis. During alkalosis, four out of eight patients with acidification defects increased their excretion of the protein. The tubular proteinuria that could be provoked during acute acidosis and alkalosis was considered to be secondary to changes in the acid-base status and may indicate a renal tubular defect.


[Tonsillar neoplasms].

[Tonsillar neoplasms]. While it is generally accepted that the treatment of choice in carcinoma of the tonsil is transcutaneous radiotherapy (including lymphatic drainage), opinion on additional surgical interventions is still divided. The possible operations are extended tonsillectomy followed by radical neck dissection or the composite operation with partial mandibulectomy. The importance of the composite operation for T3 stage tumors is emphasized. Chemotherapy (bleomycin) was rarely used in our patients, and only initially in extensive carcinoma.


[Meaningful possibilities of palliative therapy of incurable mouth and pharyngeal neoplasms and their recurrence]. In incurable cancer of the mouth and oropharynx, reasonable palliative therapy should render the patient's remaining life-span worth living. The following problems impair tumor patient's well-being: 1. pain, 2. ingestive and respiratory difficulties, 3. aspect, 4. odor, 5. psychic trauma resulting from 3 and 4. Pain, either caused by the tumor itself or as a reaction to irradiation or inflammatory response, is of primary importance. Impairment of ingestion, respiration, and speech diminishes the quality of life. Disfigurement of the face or a penetrating odor may sometimes cause additional psychic stress. Besides palliative radio- and chemotherapy, in certain cases palliation can be obtained by surgery, which may reduce the size of a cosmetically disturbing tumor mass or create a clean wound surface easier to care for than a necrotic surface. Furthermore, painful neuralgic nerve branches may be severed. Severe lymphedema of the face and neck may be improved by lumbo-peritoneal shunt operation. Most recently, cryosurgery has won an established place in the management of these problems, although certain restrictions must be observed. Superficial recurrences can be treated without further mutilation of the patient. Painful areas of the tumor can be eradicated. Recurrences in the hypopharynx, which are accessible with difficulty only, can be treated with a cryosonde with little harm to an already impaired patient. Multiple tumor lesions can be iced at the same time. Among the reasonable palliative methods of treatment, synchronized irradiation and chemotherapy as well as implantation of solid radioactive substances must be mentioned.


[The problem of the perioperative chemotherapy of the squamous epithelial carcinoma of the mouth]. In perioperative chemotherapy the question arises if, and to what extent, irritations of the wound-healing process are to be expected, especially after plastic surgery. Our research on wound-healing irritations under bleomycin therapy has been conducted in animal experiments and has resulted in definite recommendations for perioperative management. Taking UMEZAWA's experimental work as a basis, it can be assumed that the bleomycin-inactivating enzyme activity in squamous-cell carcinoma is in direct quantitative proportion to the bleomycin effect on these tumors. In clinical and experimental studies the bleomycin-inactivating enzyme activities of different squamous-cell carcinomas of the oral cavity have been tested. A lower enzyme activity - and a good clinical effect - has been found in highly differentiated carcinomas than in less differentiated and anaplastic carcinomas, with a less good effect. Reports in the literature on vascular support in carcinomas of the oral cavity prompted us to conduct microangiographic studies. Diminished vascularization with avascular regions of different size was found in most of the cases. Differentiated, medullar carcinomas showed a worse supply of blood vessels than undifferentiated and infiltrating carcinomas. The special morphological structures and functional factors of the tumor blood supply of the oral squamous-cell carcinoma are discussed in regard to their relevance for chemotherapy.


Substances moved by axonal transport and released by nerve stimulation have an innervation-like effect on muscle. Substances which have an innervation-like effect on the cholinesterase activity of organ-cultured rat extensor digitorum longus muscles are moved in nerve by axonal transport, are released from nerve by stimulation, and are present in innervated muscle but apparently absent from denervated muscle. Substances which increase the acetylcholine sensitivity of cultured muscles behave similarly.


Estrogenic activity of the insecticide kepone on the chicken oviduct. Kepone induces ovalbumin and conalbumin synthesis in explants of chick oviduct in vitro by acting as a weak estrogen. It binds to the nuclear estrogen receptor and is antagonized by the antiestrogen tamoxifen. Kepone also induces egg white protein synthesis in vivo by direct interaction with estrogen receptors and by indirectly increasing the concentration of progesterone in the serum.


Suppression of chronic allergic encephalomyelitis: relevance to multiple sclerosis. The expression of chronic relapsing experimental allergic encephalomyelitis in strain 13 guinea pigs was suppressed with a single series of injections of myelin basic protein in incomplete Freund's adjuvant. The suppression appeared permanent, and subsequent rechallenge with central nervous system antigen failed to elicit exacerbations.


Treatment of constipation in geriatric and chronically ill patients: a comparison. The difficulties of adequately managing constipation, particulary in patients with impaired or limited mobility as a result of surgery, cardiovascular or cerebral disease, or advanced age, led us to evaluate the use of stool softeners in a homogeneous group of institutionalized patients. Comparison was made between dioctyl sodium sulfosuccinate (DSS) (Colace), q.d. and b.i.d., and dioctyl calcium sulfosuccinate (DCS) (Surfak), q.d. Analysis of results showed 81% of the patients receiving DCS improved, a significant result (P is less than .02) when assessed by the sign test. By contrast, DSS caused no significant improvement over placebo, regardless of whether it was administered once or twice a day. The mean number of natural bowel movements among the DCS group increased approximately 62% over the placebo period, more than twice the 30% increase seen with DSS administered either b.i.d. or q.d. No adverse reactions were reported in any of the groups, and no significant study-induced changes occurred in laboratory measurements.


Flutamide therapy for carcinoma of the prostate. In our three-year experience with the use of flutamide for the treatment of carcinoma of the prostate, 20 patients with previously untreated stage D carcinoma of the prostate were enrolled in a 12-week double-blind study. Seven patients received 1.5 gm of flutamide daily, seven patients received 0.75 gm of flutamide daily, and six patients received 1.0 mg of diethylstilbestrol daily. Two patients receiving flutamide did not complete the 12-week study. Six patients receiving flutamide and three patients receiving diethylstilbestrol had objective evidence of improvement. Of the patients receiving flutamide, 50% were alive at one year, and 43% were alive at two years. Three of the original 14 patients started on flutamide are alive at 36, 33, and 24 months. In addition, we continued clinical evaluation of flutamide as an open study, enrolling six other patients (four with stage D and two with stage C carcinoma of the prostate). All except one of these patients had received previous hormonal therapy. At present, four are still being followed up at 13, 15, 20 and 24 months, demonstrating that flutamide can give positive results to some patients whose condition is deteriorating despite diethylstilbestrol therapy.


[Use of chlormadinone acetate (CAP) in bovine reproduction (author's transl)]. The results obtained with chlormadinone acetate (CAP) in the treatment of dairy cattle with inactive ovaries (anoestrus) and during the puerperium are reported. CAP was administered to eighteen animals with inactive ovaries for fourteen days. Oestrus occurred in fourteen animals within from one to four days after treatment had been completed. Insemination during this oestrus resulted in pregnancy in five animals. CAP was also administered to sixty animals on three farms for fourteen days during the puerperium, treatment starting on the twelfth day post partum. This was done for the purpose of improving subsequent fertility. However, as regards the interval between parturition and first insemination, the conception rate following the first insemination and the interval between parturition and conception, there were no detectable differences between the treated groups and the controls in the same herds (Table 1).


Studies on the specificity of CML. Report from a CML-workshop. In a collaboratory study involving eight different laboratories 30 human, mixed lymphocyte culture educated cytotoxic lymphocytes (CTLs) were identified yielding reproducible cytolysis on allogenic lymphocyte target cells without detectable HLA-A, B (and C) antigenic  sharing between stimulator and target cells. These CTLs were collected in one laboratory (Aarhus) and tested in parallel against a population sample of 100 unrelated, healthy Danes. The testing was only performed once and 11  CTLs did not discriminate in the population, probably due to transportation damage. On the basis of pairwise comparisons between 19 CTLs, three tentative CML-defined specificities could be recognized. These three groups may have defined monospecific traits of allelic genetic origin as judged by a mutually negative, albeit not significant, correlation and a fit to Hardy-Weinberg equilibrium. The concept of determinants other than the serologically defined HLA antigens recognized by some CTLs can thus still be maintained as can the approach to CML typing tested in this workshop.


Serological studies of Cw1 and Cw3 expressed on the same haplotype. A serological comparison has been made between individuals who are phenotypically Cw1 and Cw3. The first individual is Oriental and carries Cw1 and Cw3 on the same haplotype, the other individuals are Caucasian and carry either Cw1, Cw3 or Cw1 and Cw3 on different haplotypes. No unique specificities could be found on the Oriental Cw1, Cw3 haplotype by reciprocal absorption experiments, inhibition of complement dependent microcytotoxicity by F(ab') 2 fragments prepared from Cw1 and Cw3 antisera or by lysostrip experiments. The blocking and lysostrip experiments also suggested molecular independence of Cw1 and Cw3 determinants coded for by Oriental Cw1 haplotype. The results suggest a recent gene duplication in Oriental populations or two loci in the C region.


Association of HLA antigen a9 with progressive systemic sclerosis (scleroderma). Upon evaluation of 40 subjects with progressive systemic sclerosis (PSS), a significant association of HLA antigens A9 and Aw24 (a subgroup of A9) was found with diffuse scleroderma. HLA-Aw23 (a second subgroup of A9) was also increased in the patients, however, this was not statistically significant. Diffuse scleroderma appears to be one of the few diseases that shows an association with the HLA-A locus.


A mucoprotein with colon-specific determinants. The tissue specificity of colonic mucoprotein antigen (CMA) was examined to determine whether the antigen might have a role as a tissue marker. The immunofluorescent technique, using a rabbit anti-CMA antiserum, was employed to examine a wide range of tissues. Gastrointestinal mucosae as well as non-gastrointestinal mucin producing tissues were positive; however, non-gastrointestinal reactivity could be eliminated by the appropriate absorptions. Mucoproteins were purified separately from each gastrointestinal anatomic region and used to absorb the antiserum. This analysis demonstrated the existence of a family of mucoproteins with a common gastrointestinal specific determinant(s). Mucoproteins from neighboring regions, as seen by this antiserum, showed a greater structural similarity than did mucoproteins from distant regions. Absorption of the antiserum with ileal or cecal mucoprotein allowed the detection of a colon specific determinant present on CMA.


Relationship of HLA--D associated B lymphocyte (Ia-like) antigens in the cell membrane. The molecular relationship of HLA--D-associated by B lymphocyte antigens was studied in lysostrip, immunofluorescence and MLC inhibition experiments. Two B cell antigens, strongly associated with HLA--Dw2 and Dw3 respectively, redistributed independently of each other in the cell membrane. A more broadly reacting B cell antiserum, which apparently recognized a public antigenic structure present on B cells of different HLA-D phenotypes, coaggregated with the HLA-DW3-associated B cell antigen. Antibodies directed against the HLA-Dw2 and-Dw3 associated cell antigens caused specific stimulating cell inhibition in MLC. Less.inhibition was observed if the target B cell antigen was shared between the responding and stimulating cell donor and thus did not constitute an allogenic difference, indicating that these antigens are MLC stimulating determinants and that they reside on separate molecules in the cell membrane.


Embedding softened herbarium material in Spurr's resin for histological studies. Plant organs, including stems, rhizomes, leaves, roots, petals, sporangia and flower pedicels obtained from dried herbarium specimens of a variety of plant species have been softened with Aerosol OT and subsequently dehydrated in a graded series of acetones and embedded in Spurr's resin. Although the quality of preservation varied, sections of a variety of materials showed excellent cellular preservation. Sections stained through the resin with toluidine blue O and examined with either bright field microscopy or with crossed polarizers showed good cell detail. Histochemical tests for callose, polysaccharides, and cellulosic walls, using sections from which the resin had been removed by sodium methoxide and then viewed with an epifluorescence microscope, gave excellent results.


An efficient staining method for ultrathin sections. A staining method to handle simultaneously as many as 20 electron microscope grids is described. The devices used are easily constructed of readily obtained inexpensive materials. The volumes of stain and wash water required are very small and drying grids is simplified.


N-Butyl methacrylate and paraffin as an embedding medium for light microscopy. A method of tissue embedding using n-butyl methacrylate and paraffin is described. Following alcohol dehydration and infiltration with the methacrylate monomer, tissues are embedded in gelatin capsules in a mixture consisting of 3.5 g of paraffin for each 10 ml of methacrylate. Benzoyl peroxide (0.2 g for each 10 ml of monomer) is added as the catalyst and the methacrylate polymerized in a 50 C oven for 18--24 h. Following polymerization the block is trimmed and embedded in paraffin to provide a firm support during sectioning. A water trough attached to the microtome knife is essential to facilitate the handling of sections and ribbons. For serial sections a mixture of equal weights of beeswax and paraffin is used to make the sections adhere to each other. Usual staining procedures can be used since the embedding medium is readily soluble in xylene.


Malachite green: applications in electron microscopy. Incorporation of malachite green into a glutaraldehyde fixative results in enhanced staining of a number of cellular elements. Ribosomes and myofilaments exhibit increased electron density, but cell membranes generally are not stained. In certain tissues, lipid inclusions are uniformly and heavily stained. Other populations of lipid droplets exhibit differential affinity for malachite green, facilitating their division into subclasses. In addition to its function as a dye, malachite green has previously been reported to stabilize lipid elements soluble in aqueous glutaraldehyde. Such a component was observed in the stroma of uterine endometrium. The variety of cell components which exhibit increased contrast after preparation with malachite green suggests that this technique may find widespread application in fine structure studies.


[Drug therapy of thyroid malignomas (author's transl)]. We may recapitulate: Chemotherapy, first of all with adriamycin, has proved successful in thyroid cancer even after exhaustion of the therapeutic measures used so far. The combination of adriamycin with bleomycin and Velbe, corresponding to our preliminary experiences, seems to be superior to a monotherapy with adriamycin. The side effects remain absolutely tolerable. Hence follows concerning further procedure that chemotherapy has to be applied earlier than practiced up to now, i.e. as soon as criteria for metastasition are observed and/or if the primary treatment--operation and irradiation--does not satisfy. Cytostatic therapy apparently is the optimal treatment technique in medullar carcinoma. But it is necessary, moreover, to search for other effective combinations of chemotherapeutic agents, especially in the case of anaplastic carcinoma. Chemotherapy, assisted by thyroid hormone treatment, can certainly be improved further by a more severe assessment of the indication, by early application and, last not least, by better coordination with surgical and radiotherapeutical action.


Characterization of unoccupied (R) and occupied (RA) androgen binding components of the hyperplastic human prostate. Saturation protocols were developed for measurement of unoccupied (R) and steroid-occupied (RA) androgen binding components of human hyperplastic prostate. The concentration of unoccupied cytoplasmic binding sites (2 hr incubation at 2 degrees C) for the synthetic androgen R1881 (17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one) and the synthetic progestin R5020 (17alpha,21-dimethyl-19-norpregna-4,9-diene-3,20-dione) respectively was 10.7 +/- 1.4 and 14.3 +/- 3.2 fmoles per mg cytosol protein and the apparent steroid affinity respectively was 9.6 +/- 0.8 and 1.6 +/- 0.4 x 10(8) M-1. Steroid specificity of the unoccupied cytoplasmic R1881 and R5020 binding sites was similar. When R1881 and R5020 were employed as probes of total, R plus RA, cytoplasmic binding components (20-24 hr incubation at 15 degrees C) saturable binding of R5020 was not detectable. Total cytoplasmic R1881 binding site concentration and apparent affinity for R1881 were 51.7 +/- 3.3 fmoles per mg cytosol protein and 2.7 +/- 0.6 x 10(7) M-1. R5020 was a poor inhibitor of R1881 binding to total cytoplasmic R1881 binding components.


Major transplantation antigens of pig kidney and liver. Comparisons between the whole organs and their parenchymal constituents. We have previously shown that cultured renal and hepatic parenchymal cells of the pig differ in the expression of major transplantation antigens. Antigens apparently analogous to those of the mouse I region were detectable on kidney and some peripheral blood lymphocytes but not on liver, platelets, or other peripheral blood lymphocytes. The present study confirms these findings for liver parenchymal cells and for a mixture of kidney tubules and glomeruli prepared from fresh, perfused whole organs. However, homogenates prepared at the same time from the perfused whole organs showed no antigenic disparity. Whole liver homogenate contains I region analogues that are barely detectable on the parenchymal cell membrane. Liver parencymal cells may possess such antigens in a form not patnetly expressed, or the antigens may belong to other types of cell resident in the liver which are not removed by extensive perfusion. Similar results were obtained with liver homogenates derived from an orthotopic transplant to a fully allogeneic recipient and resident for 37 days, suggesting that blood lymphocytes persisting in the normal liver after perfusion could not account for these findings.


A histochemical study of glycosidases in benign prostatic hyperplasia and in prostatic carcinoma in the human. In benign hyperplasia marked beta-glucuronidase and N-acetyl-beta-glucosaminidase activity was seen in the prostatic epithelium whereas the reactions for 5 other glycosidases were only slight or negative. The intensity of the reaction for the glycosidases in prostatic carcinoma was dependent upon the degree of the differentiation. The possible importance of glycosidases for the invasiveness of prostatic carcinoma is briefly discussed.


Basal cell adenoma of prostate.

Basal cell adenoma of prostate. A case of basal cell adenoma originating in the prostate is presented. This lesion might develop from proliferation of basal epithelial cells of the prostate gland under unknown mechanism.


[Effect of peridural anesthesia on kidney function]. A complex study of hemodynamics and renal function in 30 patients with adenoma of the prostate during peridural anesthesia has been carried out. The functional renal reaction depends upon the scope of the sympathetic blocade in peridural anesthesia and bears an intimate relation to hemodynamic and neurohumoral effects of the developing blocade. All these changes are of a temporary character and regain values close to the initial ones by the time of the adaptation of the body to peridural anesthesia and stabilization of hemodynamics.


A coated-tube radioimmunoassay (FRC-RIA) for hepatitis B surface antigen. A sandwich-type solid phase radioimmunoassay, FRC-RIA (Finnish Red Cross-RIA) for hepatitis B surface antigen (HBsAg) is described. Polystyrene test tubes coated with sheep anti-HBs gamma-globulin serve as the solid phase. The technique is specific and has a sensitivity of about 1 ng/ml for the subtypes ad and ay of HBsAg when corresponding subtype-specific antibodies are used as reagents. The total incubation time can be shortened from over 20 h to 3 h, with almost equal sensitivity, when the incubation temperature is raised from room temperature to 45 degrees C. The test is economical in reagents and is applicable to routine use.


[Isolation and analysis of encephalitogenic fractions of spinal cord proteins]. Main encephalitogenic protein was isolated from bovine medulla spinalis and separated into homogenous polypeptide fractions by gel filtration; some of these fractions had the high encephalitogenic activity. The main protein and its fractions, possessing the encephalitogenic activity, caused a development of cross-reacting antibodies and a sensitization to intracutaneous administration of encephalitogenic preparations in animals. Non-encephalitogenic main protein sensitized animals only to this protein and did not induce the formation of distinct amount of antibodies. The amino acid composition of the encephalitogenic polypeptide is exhibited.


[Therapeutic effect of myelin basic protein and synthetic encephalitogenic peptide in guinea pigs with experimental allergic encephalomyelitis]. Effect of antigenic factors of experimental allergic encephalomyelitis (alkaline protein of myelin and synthetic encephalitogenic peptide) was studied in guinea pigs with distinct manifestations of the experimental allergic encephalomyelitis. The animals recovered after prolonged administration of alkaline protein of myelin within 14 days, if they were sensibilized either by bovine alkaline protein of myelin or by synthetic encephalitogenic peptide. Synthetic encephalitogenic peptide was only effective in treatment of the disease caused by the peptide.


[Spontaneous deamidation of gamma-globulin]. gamma-Globulin from human blood serum was incubated in thermostat at 37 degrees within 15, 30, 45, 60 and 72 days. Amount of readily and poorly hydrolyzed amide groups as well as an increase in amino acid content were estimated in the protein at zero time and at these periods. The sterility of the preparation was examined in each case. Spontaneous deamidation of gamma-globulin, observed during incubation, caused an increase in negative charge and altered electrophoretic mobility of the protein molecule. gamma-Globulin was attacked by prothelin more effectively as amount of amide groups was decreased in the protein. Spontaneous deamidation appears to be one of reasons of the protein molecules ageing.


A rapid, simple, and reliable technique for preparation of antisera against idiotypes of homogeneous immunoglobulins. One-step immunization of guinea pigs with homogeneous immunoglobulins partly purified by micro-agar electrophoresis represents a rapid and reliable microtechnique for the preparation of antisera against the idiotype of the homogeneous immunoglobulins. Testing of these antisera by immunodiffusion techniques requires agar plates containing 3% polyethyleneglycol 6000.


[Isolation and purification of specific beta1-G-globulin]. Antigen, specific for trophoblastic tumor, was isolated from retroplacental blood by means of ion exchange  chromatography on DEAE cellulose, gel filtration on Sephadex G-200, chromatography on hydroxylapatite and CM-cellulose and by preparative isofocusing using ampholines. Distinct heterogeneity of the protein and alteration in several its properties were observed as purity of the preparation was increased in course of isolation. A series of the protein preparations was obtained with 90-95% purity and with similar immunologic properties but the preparations differed in electrophoretic mobility, isoelectric points and some other patterns.


Nomenclature for factors of the HLA system--1977. A Nomenclature Committee composed of geneticists and immunologists, including specialists in tissue typing, has met after each of the Histocompatibility Testing Workshops beginning with the 3rd Workshop in 1967. The Committee met again, in part under the auspices of the World Health Organisation and for report to the International Union of Immunological Societies, after the 7th Workshop in Oxford in September 1977, with the aim of updating the nomenclature for specificities of the HLA-A, B, C and D loci and establishing a nomenclature for the new specificities identified by serological techniques on B lymphocytes.


ND1, a new neutrophil granulocyte antigen. The serum of 2 patients suffering from autoimmune neutrophil granulocytopenia contained autoantibodies that were directed against a new granulocyte-specific antigen. Genetic analysis showed that this new antigen was not correlated with the already known neutrophil antigens, NA1, NA2, NB1, NC1 or 9a. This was studied in a four-generation family. In the Dutch population the frequency of the antigen, tentatively called ND1, is 98.5% (n = 67), pointing to a gene frequency of 0.88.


[Antigenic specificity of influenza type A virus hemagglutinin by the method of radioimmunological quantitative analysis]. The use of a test system o fa highly purified, antigenically homogeneus hemagglutinin of influenza A/MRC-11 virus and monospecific antiserum permitted to evaluate the potentials of competitive radioimmunoassay in model experiments investigating the antigenic characteristics and content of influenza A (H3N2) virus hemagglutinin. The method proved to be sufficiently specific to differentiate influenza virus strains by antigenic determinants of hemagglutinin, as well as highly sensitive, detecting very small (down to 1 ng) amounts of H3 hemagglutinin in a sample.