Influence of HLA matching and blood-transfusion on outcome of 502 London Transplant Group renal-graft recipients. The outcome of 502 cadaver kidney transplants has been followed for up to six years; these grafts were arranged through the Tissue Immunology Unit of the London Hospital Medical College, the coordinating centre of the London Transplant Group. An analysis of HLA (A and B) recepient-donor matching revealed, as in previous analyses, clear differences (now highly significant) between the best as compared with the lesser matched recipients. A quarter of the patients (group 4 and 3a) had a superior outcome 20-30% greater than poorly matched (2 or less group) which constituted 53% of individuals. The results in the 3b group (28% of patients) were intermediate 10-15% better than the "2 or less antigens in common" group. A small number of recipients mostly 4 or 3 matched who were retrospectively HLA-D matched showed an even better graft survival. The effect of blood-transfusion before transplantation was studied and found to improve the outlook especially in the best-matched groups. No difference was apparent between those receiving less or more than ten units except in a group of patients with cytotoxic antibodies and/or retransplants. This "immunocompetent-presensitised" group had the best outcome provided these recipients had few transfusions and were subsequently well matched. These findings emphasise the continued need for successful collaborative associations, so that improved matching can be achieved which if universally applied would ensure better graft survival for a large number of patients in renal failure.


First-line chemotherapy in the retreatment of bacteriological relapses of pulmonary tuberculosis following a shortcourse regimen. Totals of 404 Chinese and 778 East African patients with newly diagnosed drug-sensitive pulmonary tuberculosis were treated with short-course regiments of antituberculosis chemotherapy. The Chinese received 6-month and 9-month regimens of streptomycin plus isoniazid plus pyrazinamide, and the East Africans 6-month regiments of streptomycin plus isoniazid alone or with a third drug. 28 Chinese and 45 African patients who relapsed with drug-sensitive strains after their short-course regimen were retreated with standard first-line chemotherapy. The Chinese were given every single dose under full supervision, but the Africans the initial phase only. At 12 months from the start of their retreatment, all 28 Chinese and 40 (89%) of the 45 Africans had a favourable therapeutic response on their retreatment regimen. 2 of the 5 East African patients whose retreatment failed were known to have been irregular in taking their drugs.


Beneficial effects of methylprednisolone "pulse" therapy in diffuse proliferative lupus nephritis. Seven patients with diffuse proliferative lupus nephritis were subjected to highdose intravenous methylprednisolone (pulse) therapy. Following the pulse, five patients with rapidly deteriorating ranal function improved within three days and their serum-creatinine levels returned to baseline by one month. All seven patients demonstrated reversal of severe immunological abnormalities including increased serum D.N.A binding, decreased serum C3 levels, and reduced number of T lymphocytes in the peripheral blood. This form of therapy may make it possible to maintain patients with lupus nephritis on lower doses of steroids than is normally feasible.


Leukaemia-associated antigen in serum of patients with acute lymphoblastic leukaemia. A antigen (HThy-L) previously found in extracts of human thymocytes and leukalphaemic cells was detected in sera from four patients with E-rosette-positive untreated acute lymphoblastic leukalphaemia (A.L.L.) and one patient with previously treated acute myelogenous leukaemia (A.M.L.) The disappearance HYth-L angignaplhaemia with treatment was coindent with a decrease in the number of leukaemic blast cells in the peripheral blood. HThy-L antigen was not detected in the sera of the remaining twenty-one patients with E-rosette-negative A.L.L. and seven patients with A.M.L..


IgA deficiency and severe post-vagotomy diarrhoea. Between January, 1969, and December, 1973, 2058 truncal vagotomies were performed in the Merseyside Regional Health Authority area. 14 of these patients subsequently developed severe post-vagotomy diarrhoea and were extensively investigated. 6 were found to have IgA deficiency. It is suggested that antecedent IgA deficiency may account for the varied reported incidence of severe post-vagotomy diarrhoea and that preoperative screening could reduce the incidence of this complication.


Is vasopressin involved in the pathogenesis of malignant desoxycorticosterone hypertension in rats? Rats with unilateral nephrectomy were offered 1% sodium chloride as drinking fluid and were injected with desoxycorticosterone trimethylacetate (D.O.C.-T.M.A.) at weekly intervals. During the fourth to seventh week after the start of the experiment, malignant hypertension developed in most  of the animals: body weight fell, reflecting volume depletion; serum osmolality and serum sodium and urea concentrations increased; in the kidneys malignant nephrosclerosis occurred. In such animals, plasma concentrations of arginine-vasopressin were increased ten-fold in comparison with control animals; intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood-pressure (B.P.) to normal or subnormal levels, while the injection of an angiotensin-I or angiotensin-II antibody did not affect B.P. In control animals none of the antibodies had an effect on B.P. It is concluded that in the pathogenesis of malignant D.O.C. hypertension vasopressin plays a role similar to that of renin-angiotensin in malignant renal hypertension.


Possible selection of virulent poliovirus strains in Third-World countries. In Kenya for more than twenty years a remarkable periodicity has been observed in the circulation of type-1 poliovirus and in epidemics of poliomyelitis caused by this virus type. Periodicity was less obvious for poliovirus types 2 and 3. Cases of poliomyelitis increased, and this trend was only partly controlled by vaccination. It is postulated that virulent strains of poliovirus became dominant because of selection pressure. It is suggested that this selection pressure occurred earlier in economically developed countries and was partly responsible for the pronounced changes in the epidemiology of poliomyelitis seen in such countries.


Allelic restriction: a biologic alternative to multifactorial threshold inheritance. Contrary to the argument regarding the conservatism of the multifactorial threshold model for describing the inheritance of congenital malformations, little biological insight has resulted from the series of tautological, albeit grandiose, mathematical assumptions currently comprising the basis for this hypothesis. The working hypothesis of this presentation is to apply the "allelic restriction" model to the genesis of common human congenital malformations. New population data concerning isolated cleft palate closely fit the predictions of the proposed hypothesis. Recognising the heterogeneity of cleft palate as well as other common congenital malformations (namely, the difference between phenocopies, definable syndromes, and true hereditary cases), the "allelic restriction" model accords with the apparent greatly "reduced penetrance" of the heriditary cases. This model is meant to apply only to those congenital malformations which have both a high population frequency and a relatively small number of families showing an atypical type of vertical transmission.


Hypoxic cell sensitisers in radiotherapy. Solid tumours contain poorly oxygenated cells, and these are disproportionately resistant to therapeutic radiation. Several methods of overcoming this problem have been used clinically, including the administration of hyperbaric oxygen during irradiation, radiotherapy with heavy nuclear particles such as neutrons from cyclotrons, optimum size and spacing of multiple doses of conventional radiation, and, most recently, chemical radiosensitisers. These radiosensitisers mimic the sensitising effect of oxygen and are active only against hypoxic cells. They do not, therefore, increase radiation response in well-oxygenated normal tissues. They are not rapidly metabollised and so can penetrate further than oxygen from the vascular capillaries and effectively reach the hypoxic cells in the tumour. Some of these drugs are of considerable clinical promise. The results of in vitro and in vivo studies with radiosensitisers are summarised and preliminary clinical work is described.


Parent-to-child and child-to-parent kidney transplants. Experience with 101 transplants at one centre. 101 first transplants were done in patients with end-stage renal disease using kidneys from parents or offspring. All patients were followed up for at least two years, and the absolute two-year patient-survival rate was 88% and the two-year functional-kidney rate was 79%. Actuarial statistics at four years were 82% for survival and 67% for function in the parent-to-child group. In the child-to-parent group absolute patient survival was 83% and transplant function was 79% at two years; these results were unchanged at four years. Thus, transplants from parents to children or from children to parents are much the same despite differences in age. There is some advantage in parent-to-child transplants from being female but no advantage in being diabetic, receiving higher or lower doses of antilymphocyte globulin, or sharing more than two HLA antigens with the donor. Mismatched sibling transplants survived approximately as well as did grafts from parents to children and children to parents. These results, taken in concert with the poor results of cadaver transplantation, the relative safety of donation, the high personal motivation to donate in these groups, and the personal satisfaction derived by the donor, strongly support the policy of informing potential recipients of the benefits of parental or offspring kidney donation.


Sodium excretion and sympathetic activity in relation to severity of hypertensive disease. The relationship between the severity of hypertensive disease and sodium excretion and sympathetic activity has been studied in subjects of the same age and sex derived from screening a total population. 19 untreated subjects with casual blood-pressure (B.P.) above 175/115 mm Hg on two separate occasions made up the hypertensive group. A normotensive group (n =19) was obtained by selecting a 5% random sample from all subjects with casual B.P. below 160/95. Sympathetic activity was determined from noradrenaline excretion and the severity of hypertension assessed by recording resting diastolic B.P., signs of left ventricular hypertrophy on orthogonal E.C.G., and the glomerular filtration-rate. In the hypertensive group the resting B.P. correlated well both with signs of left ventricular hypertrophy and with the glomerular filtration-rate--i.e., the degree of severity of the hypertension. Up to the level of 90 mm Hg resting diastolic B.P., sodium excretion rose in complete agreement with the theory of pressure diuresis. Above 90 mm Hg, however, sodium and noradrenaline excretion fell with increase of B.P. These two findings indicated that with increasing severity of hypertension the sodium balance overrides the sympathetic activity in the long-term regulation of B.P. This may have both prognostic and therapeutic implications.


Pancreatic polypeptide in insulinomas, gastrinomas, vipomas, and glucagonomas. In 33 patients studied with endocrine neoplasms of the pancreas more than half the tumours contained pancreatic polypeptide (P.P.) producing cells, and a high radioimmunoassayable concentration of P.P. was found in the tumour extracts. Plasma was available from 28 patients, and very high circulating P.P. concentrations were found in 18. The presence of P.P. in hepatic and lymphnode metastases indicates that its production by the primary neoplasm cannot be ascribed to incidental adherence of normal P.P. cells. Measurements of plasma P.P. levels should be a new aid to diagnosis of pancreatic tumours.


T and B lymphocytes in breast cancer stage relationship and abrogation of T-lymphocyte depression by enzyme treatment in vitro. B and T lymphocytes have been measured in 100 women--71 patients with breast cancer and 29 controls--using sheep-erythrocyte rosetting techniques. Compared with controls (healthy women or patients with benign breast disease), there is a highly significant depression of T-cell percentage in all stages of breast cancer except locally advanced (stage 3) disease. These stage-3 cases seem to constitute a biologically distinct group. T-cell percentages in early (stage 1) patients overlap with those seen in stages 3 and 4, raising the possibility that there are in stage 1 two subpopulations of T-cell values that are associated with differences in subsequent tumour progression. B-lymphocyte levels are similar in all groups. Low T-cell levels return to normal after incubation with papain in virto but fall again after resuspending the treated lymphocytes in autologous (cancer) serum. The results suggest that T-cell depression is due to a masking factor on the surface of some T lymphocytes which is also present in the serum of cancer patients, and removable by enzyme digestion.


Anti-mite measurements in mite-sensitive adult asthma. A controlled trial. A cross-over controlled trial has been conducted among 32 adult patients with mite-sensitive asthma. The bedclothes and pillows of each subject were laundered and vacuum-cleaned and a plastic cover applied to the mattress for six weeks in an attempt to reduce exposure to mites. No improvement in daily peak-flow reading or drug usage was found in comparison with a control period.


Diarrhoea caused by Candida.

Diarrhoea caused by Candida. Candida proliferation in the gastrointestinal tract was responsible for diarrhoea in six patients. Their common presentation was multiple loose or watery bowel movements, without blood or mucus but sometimes associated with abdominal cramps, and lasting as long as 3 months. Yeast cells were most easily identified by direct microscopic examination of stool specimens. Symptoms disappeared in all patients after 3 to 4 days of oral nystatin therapy.


Healing of gastric ulcer during treatment with cimetidine. 10 patients with benign gastric ulcer were treated with cimetidine 0-8 to 1-6 g/day for six weeks. Relief of symptoms was rapid. Endoscopy at the end of treatment showed that all the ulcers had healed. Healing was not associated with an improvement of acute atrophic gastritis nor with any change of gastric mucosal potential difference. No untoward clinical or laboratory effects were observed.


Non-specific cytotoxicity of wheat gliadin components towards cultured human cells. Chromatographically separated fractions of a proteolytic digest of wheat gliadin were assayed for cytotoxic properties using cultured human embryonic intestinal, lung, kidney, adrenal, and HEp-2 cells. In all cell types noxious effects were observed microscopically over a 24 h period. The most active fraction was that previously shown to produce xylose malabsorption in subjects with coeliac disease, disruption of lysosomes, and inhibition of morphological recovery of cultured mucosa from a patient on a gluten-free diet.


Cyclic adenosine monophosphate, ventricular fibrillation, and antiarrhythmic drugs. It is proposed that the development of ventricular fibrillation in the context of ischaemic heart-disease and myocardial infarction can be related to accumulation of cyclic adenosine 3',5' monophosphate (A.M.P.) in the ischaemic zone. The known electrophysiological and metabolic actions of cyclic A.M.P. are consonant with the hypothesis, which also provides a framework for the better understanding of the action of antiarrhythmic drugs.


Diagnostic x-rays in late pregnancy and in the neonate. A survey has been carried out of current practice of radiology in late pregnancy and in neonates in the U.K. In major hospital centres, up to 34-8% of all pregnancies are still X-rayed, as well as up to 10% of neonates. It is suggested that criteria for X-ray examinations in late pregnancy and of the neonate need closer scrutiny.


Matching quality of agents employed in "double-blind" controlled clinical trials. In an inquiry into the matching quality of preparations employed in double-blind controlled clinical trials, a panel of 4 observers studied 22 pairs of agents used in a sample of such trials, examining features which might make one preparation distinguishable from the other. 5 pairs of substances were an excellent match, being virtually indistinguishable, but in 7 pairs ther were obvious differences, detected by all 4 observers. The preparations used in cross-over studies were not specially well matched. Colour differences were most readily detected, followed by taste. The observers differed in their ability to detect differences between pairs of preparations, and 1 panel member was approximately 3 times more successful in doing so than another.


Effect of intravenous prednisolone in asthmatics with diminished adrenergic responsiveness. The beta effects of adrenergic stimulation are often diminished in asthmatics in whom the condition is active. Corticosteroids are thought to lower the threshold of beta-adrenergic receptors to the response of catecholamines. A single intravenous injection of 40 mg prednisolone appeared to restore responsiveness to inhaled isoprenaline in eight out of ten chronic asthmatics who were previously non-responsive to catecholamines.


Evidence of a viral aetiology in endemic (Balkan) nephropathy. Segemental and focal pathological changes were found in the glomeruli and tubules of postoperative renal-biopsy specimens from seven cases of clinically confirmed endemic (Balkan) nephropathy. In the glomeruli, there was mesangial reaction and segmental thickening of the basement membrane with subendothelial and membranous depositions. In the tubules there was spongiform degeneration and fusion of cells. In all the cells of the nephron numerous cytoplasmic vesicles containing free and budding particles (80-200 nm) were found. These particles had the characteristics of a coronarivus. Balkan nephropathy occurs almost exclusively in people who have been in close contact with pigs. Coronaviruses have been isolated from pigs, and it is suggested that a slow coronavirus infection causes endemic nephropathy in man.


Platelet abnormalities in diabetic peripheral neuropathy. Abnormal platelet function has been demonstrated in 20 patients with diabetic peripheral neuropathy. The results are compared to those obtained from 19 matched diabetic patients with no clinical evidence of complications and 20 matched normal control subjects. Platelets from patients with diabetic neuropathy showed an increased sensitivity to the aggregating agents adenosine diphosphate and adrenaline. Spontaneous platelet aggregation was demonstrated in both groups of diabetic patients.


Endovesical electrotherapy in treatment of urinary incontinence in spina-bifida patients. A total of 20 children with incontinence due to myelomeningocele and 1 due to occult neuropathic bladder underwent a course of endovesical electrotherapy. There was temporary improvement in 1 and more lasting in another, but this was the result of catheterisation and bladder training rather than the electrotherapy. It is concluded that the electrotherapy has helped none of the patients, and no significant change in their bladder function was detected.


Serum triiodothyronine and reverse triiodothyronine concentrations after surgical operation. Serum-triiodothyronine (T3) concentrations fell rapidly after surgery in six out of seven initially euthyroid patients. Simultaneous increases in reverse triiodothyronine (rT3) concentrations suggested that the peripheral monodeiodination of thyroxine (T4) proceeds by an alternative pathway in the postoperative period.


Clofibrate-induced muscle damage in patients with chronic renal failure. Muscle weakness and tenderness together with a rise in serum creatine kinase (C.K.) were noted in five uraemic patients treated with 1-2 g of clofibrate ('Atromid-S') daily. Excessive accumulation of both total and free serum chlorophenoxyisobutyric acid (C.P.I.B.), the active circulating metabolite after clofibrate therapy, was found in three patients in whom it was sought. It is suggested that chronic renal failure should be regarded as a contraindication to the use of clofibrate for the treatment of any coexisting hyperlipidaemia. If such therapy is contemplated it must be cautiously instituted at low dosage and the patient monitored by regular assessment of serum C.K. and levels of both total and free C.P.I.B.


Chromosome abnormalities in Dupuytren's disease. Palmar fascia from six men with Dupuytren's contracture has been grown in tissue-culture and examined cytogenetically; and in three of these cases skin was also studied. Four of the six cases showed mosaicism, but only in cultures of the fascia; the mosaicism was therefore unlikely to be an artefact. Since the abnormalities were inconsistent and absent from skin-cultures they are very unlikely to indicate any mechanism of inheritance. Similar chromosome abnormalities have been reported from experimentally induced tumours.


How does blood-pressure cause stroke?

How does blood-pressure cause stroke? In chronic hypertension the specific arterial lesions responsible for brain damage affect the small resistance arteries. The pathological characteristics of these lesions (notably the presence of microaneurysms, intramural fibrin, and lipid) and the location of lesions within the brain all suggest that they arise from mechanical distension, which destroys the integrity of the vessel and allows plasma insudation into the wall (lipohyalinosis), finally leading to occlusion or rupture. The process in analogous to the breakdown in vascular resistance and permeability which occurs in acute hypertension.


Is early decline of cardiac function in ischaemia due to carbon-dioxide retention? There is no satisfactory explanation for the early and rapid decline of cardiac muscle function in ischaemia. Reduction of the energy source for contraction, A.T.P., is insufficient in magnitude and too slow in onset to be the prime cause. It is proposed that a large part of the loss of function is directly attributable to an immediate fall of intracellular pH and results from the accumulation of carbon dioxide and lactic acid; the intracellular acidosis reduces myocardial function by inhibition of that part of the calcium-ion influx associated with contraction.


Comparison of E.M.I. and radioisotope imaging in neurological disease. A comparison has been made between the information provided by isotope imaging--before and after the introduction of E.M.I.-scanning--and E.M.I.-scanning itself. E.M.I.-scanning is superior to isotope imaging (also called scintigraphy) with the gamma camera and the rectilinear scanner in the amount and quality of information provided.


[Further in-vitro studies on the mechanism of hyperacute xenogenic rejection reaction (HXAR)]. Rat kidneys (donor organs) were perfused in an in-vitro perfusion circuit using blood or modified blood from the dog (recipient). Hyperacute xenogeneic rejection (HXR) in widely divergent species system could even be seen, when preformed natural antibodies were absent. These data presented suggest that this form of HXR is at least partially induced by nonspecific (equals nonimmunologic complement activation, followed by complement mediated disease (liberation of vasoactive and other substances leading to increased permeability. e. g. Anaphylatoxin) of the donor kidneys.


[Blood picture changes following single and prolonged oral application of ALG in the dog]. Mongrel dogs were orally treated with 20 mg/kg ALG or NHG respectively. A significant decrease of the peripheral lymphocyte count was observed not only during 6 hours after the application of ALG but also during longtime observation. This lymphocytopenia was found to be between 30% and 50%. The effect of ALG after oral administration is smaller than after i. v. application. All other blood cells remained essentially unaffected by ALG as well as NHG. Whereas the efficacy of i. v. applied ALG is reduced by antibody formation, this cannot be expected to the same degree during oral administration, because the antibody formation is markedly reduced by the oral route of application.


[Determination of intravasal volume loss in arteria mesenterica superior shock in the rat and attempt for adequate substitution therapy]. In ams-shock of rats the weight of the small bowel contents of an animal 310 g of weight increases from 2.5 g to 13.0 g. The fluid loss into the bowel lumen amounts to 10.5 g and exceeds the plasma volume of 9.6 g. Drainage into the large bowel is not taken into consideration. After treatment of the ams-shock with gelatine infusion the weight of the small bowel wall increases significantly for a limited period of time to 3.2 g% body weight compared to normal controls with 2.3 g% body weight. After at least 24 hours the necrotic epithelium of the small bowel is fully recovered. Following ams-shock it is possible by means of gelatine infusion to improve the time and rate of survival significantly and to give support to the theory of volume loss.


[Storage of histamine in the blood following liberation from liver and antrum through trypsin: protective mechanism or a factor promoting pancreatic shock]. In dogs histamine was predominantly released from liver and antrum by intravenous injection of trypsin. The histamine content of the human liver was found to be high enough to allow the invasion of mg amounts of histamine into the circulation after histamine release. In blood histamine was rapidly taken up by corpuscular elements. At present it cannot be decided whether this mechanism leads to detoxification or to a more powerful action of histamine in the microcirculation.


[Role of plasma and gastric histamine under conditions of stress in patients]. In patients with stress bleeding and severe burns, histamine levels in plasma and in gastric juice were significantly elevated compared with a control group (patients with abdominal operations and uncomplicated postoperative course).


[Histamine liberation in man following plasma substitution with gelatine and dextran: cause of anaphylactic reactions in the hospital?]. After rapid gelatin infusion in many cases a release of relatively small amounts of histamine was observed. Clinical symptoms occured in 5 cases in correspondence to the increased histamine levels, but were relatively harmless. The application of dextran 60 induced anaphylactoid reactions in 2 persons, with death in one case. Plasma histamine level were normal in both cases. Histamine release probably is not the cause of dextrn induced anaphylactoid reactions.


[Evaluation of results of surgery (author's transl)]. A computerized documentation system for the evaluation of arterial reconstructive procedures has been in practical use within the Austrian Society for Vascular Surgery since 1969. Early and late results of 2103 operations preformed at the 1st Surgical Clinic of the University of Vienna for chronic occlusive disease of the lower extremities are analyzed for function of arterial reconstruction, amputation rate and mortality and the dependence of these on the preoperative stage and the localisation of the occlusion.


[Carcinoma of the pancreas: palliative surgery (author's transl)]. Among 1146 patients with diseases of the pancreas observed over a 15-year period, there were 234 cases of malignant duodeno-pancreatic tumors. This report concerns the intraoperative diagnostic methods and the various palliative operations available. There was a ratio of 13 males to 10 females, and the average age was 63 years. In 24.3 percent of the patients attempts to establish the diagnosis intraoperatively by puncture or excision were unsuccessful. The cardinal symptom in 71 percent of these cases was icterus. Duodenopancreatectomy was possible only in 21 cases (= 8.9%). In 173 cases (= 75.2% of all patients) a palliative operation was performed.


[Carcinoma of the pancreas: curative operations (author's transl)]. In 1898 the first radical operation for carcinoma of the pancreas was performed by Codivilla in Bologna. Kausch followed in 1913 and Whipple perfected the technique of duodenopancreatectomy. The central position of the pancreas causes technical difficulties. Carcinoma of the head of the pancreas frequently causes icterus, which quite often limits the primary radical operation. Radical removal of carcinoma of the head of the pancreas is only possible if the limits of the organ have not been passed. Preservation of a part of the pancreas is essential for the metabolism. The average primary mortality of the radical operation is around 25 percent, having fallen significantly in the last few years. The 5-years recovery rate is a bare 10 percent.


[Carcinochemotherapy in incurable cancer? (author's transl)]. Despite the rapid advances in carcinochemotherapy, the possibilities for the treatment of solid tumors are rather limited, so that the advantages and disadvantages of chemotherapy must be very carefullly considered in each case of incurable cancer. It should also be emphasized that there are several tumor types in which skillfull application of chemotherapy does not only lead to an objective improvement in the clinical findings but also prolongs the patient's life.


[Basic features in immunohistological technique (author's transl)]. Light and electron microscopic demonstration of antigens in tissue is possible by means of labelled antibodies. Direct and indirect immuno-fluorescence techniques and recently also the peroxidase method permit a broader application of this principle. The peroxidase technique has the advantage of requiring less equipment and of providing the possibility to obtain durable specimens. The fluorescence technique permits the association of fluorescence phenomena with certain tissue structures by means of secondary "staining", for instance localization of specific hormone production sites. This allows functional morphological deductions in healthy and pathological conditions. Flawless techniques and controls are required before a specific reaction can be acknowledged since auto-fluorescence phenomena as well as pseudo-specific and cross-reactions are sources of error leading to wrong conclusions. A standardization of methods must therefore be attempted.


A rapid and simplified staining of juxtaglomerular granules with aqueous crystal violet. The method described allows staining of juxtaglomerular granules in a deep purple colour against faint purple background and deep purple erythrocytes. Paraffin sections of mouse kidney fixed in 10% formalin buffered with phosphate are brought to water, stained 3 min in 0.01% crystal violet, rinsed in tap water (or stained 3 min in 0.1% crystal violet in NaHCO3, rinsed in 1% NaHCO3), blotted, differentiated in a 1 : 1 aniline-xylene mixture, cleared in xylene and mounted in a resin.


Observations on the relief of pancreatic pain. Disabling pain of pancreatic origin can be relieved by drugs, by direct surgery to the pancreas, or by denervation of the pancreas. The place of each is discussed in the management of pancreatic pain. The special role of a coeliac plexus block in these cases is emphasized and the technique of its performance is described in detail.


[The role of chlorazepate dipotassium (Tranxilium) in the therapy of psychosomatic syndromes (author's transl)]. Divided into four groups according to different kind and cause of disorder, 240 patients showing psychosomatic disorders have been treated with chlorazepate dipotassium only or in combination with clomipramine and dihydroergotamine tartrate ambulant or in hospital, depending on the degree of severity of the disorder. With 101 clinically treated cases of cyclothymic depression good results were obtained with combined treatment with chlorazepate dipotassium while reducing the dose of the antidepressant. The same result was obtained with 63 patients suffering from severe neurasthenic exhaustion and 13 patients with general neurodystonic symptoms treated with chlorazepate dipotassium only. The combination of the usual dihydroergotamine tartrate medication with a chlorazepate dipotassium treatment over several months showed longlasting good therapeutic results, confirmed by follow-up examinations, in 31 out of 40 cases with migraine respectively vasomotor headache. In the other nine patients with migraine the complaints persisted only in rare instances.


Studies on bacteriophage T7 DNA synthesis in vitro. II. Reconstitution of the T7 replication system using purified proteins. DNA synthesis in vitro using intact duplex T7 DNA as template is dependent on a novel group of three phage T7-induced proteins: DNA-priming protein (activity which complements a cell extract lacking the T7 gene 4-protein), T7 DNA polymerase (gene 5-protein plus host factor), and T7 DNA-binding protein. The reaction requires, in addition to the four deoxyribonucleoside triphosphates, all four ribonucleoside triphosphates and is inhibited by low concentrations of actinomycin D. Evidence is presented that the priming protein serves as a novel RNA polymerase to form a priming segment which is subsequently extended by T7 DNA polymerase. T7 RNA polymerase (gene 1-protein) can only partially substitute for the DNA-priming protein. At 30 degrees C, deoxyribonucleotide incorporation proceeds for more than 2 hours and the amount of newly synthesized DNA can exceed the amount of template DNA by 10-fold. The products of synthesis are not covalently attached to the template and sediment as short (12S) DNA chains in alkaline sucrose gradients. Sealing of these fragments into DNA of higher molecular weight requires the presence of E.coli DNA polymerase I and T7 ligase. Examination of the products in the electron microscope reveals many large, forked molecules and a few "eye"-shaped structures resembling the early replicative intermediates normally observed in vivo.


[Light- and electron-microscopic changes in liver cells of a patient with acute liver damage caused by Lindane]. Acute liver-lesion was observed in a 77 years old women, using a preparate "Hungaria L. 7" consisting 7,8 percent of Lindan, without keeping directions for use. In 24 hours onset of toxic exanthema, lack of appetite, and abdominal pains were seen. After a longlasting discomfort and loss of weight on the 4th week jaundice have occurred. In the liver biopsy specimen microscopically centrolobular necrosis of lytic type, steatosis and a moderate periportal inflammatory reaction was revealed. On the electron micrographs steatosis and paralelly arranged osmiophilic inclusions in the mitochondria seemed to the most characteristic feature. Authors stress that in cases of acute liver lesions careful analysis of the history may evidence a toxic origin of the lesion, and the latter morfologically--as it is demonstrated in the presented case--can be distinguished from the acute virus-hepatitis.


[Experimental study of the hepatotoxic effect of toluol. I. Histological and histochemical studies]. The hepatotoxic effect of the analytically pure toluol and a toluol being used in the Chemical Factory "Tiszai" was investigated. Single toxic- and various subtoxic doses of toluol were administered to male rats of CFY intraperitoneally and subcutaneously. The body weight and the weight of the liver were registered. Histological and histochemical study of the liver have also been carried out. After an acute and subacute toluol intoxication decrease of the PAS-positive and Bestcarmin positive material in the liver and increase of the activity of SDH were observed. The degree of the damage to the hepatic tissue depends on the doses of toluol and on the duration of the administration. It is stressed that a severe damage to the whole liver was not seen in any of the experimental animals. There was not any difference noticed between the lesions caused by the different types of toluol.


[Intraoperative rapid cytological assessment of mammary tumors (author's transl)]. A quick staining technique is reported which permits a full cytological statement on the seriousness of mammary tumors within 2 minutes intraoperatively. The accuracy of the method is comparable to that of histological examination. Between 1971 and 1974 a cytological rapid examination was carried out for the assessment of the seriousness of a total of 409 mammary tumors intraoperatively. 71 (equals 17.5 per cent) of the 409 tumors were carcinomas. In 70 of the carcinomas, the severity was confirmed histologically. The method can also be performed in small hospitals which have no pathology laboratory available.


Genetic activity of niridazole in yeast. Niridazole, one of several drugs presently known to be of value in the treatment of human schistosomiasis, was tested for its activity in inducing mitotic recombination in yeast. It was found that niridazole is genetically active when the treatment of yeast cells is performed in a rich medium (YPG-medium) under growing conditions, but not when treatment is carried out in a non-nutrient suspension (phosphate buffer). The data suggest that niridazole might be converted to an active compound by yeast metabolism. The results of the experiments with niridazole in the non-nutrient medium were compared with those of AF-2 and SQ18, 506, two agents which have been shown to be genetically active in the present assay system.


Genetic association of multiple sclerosis and HL-A determinants. Segregation of HL-A haplotypes was analyzed in 10 families in which there were at least two cases of multiple sclerosis. In nine families, multiple sclerosis was associated with only one parental HL-A haplotype. Specific HL-A determinants associated with multiple sclerosis differed among the families, suggesting that another histocompatibility-linked factor, possibly a gene determining susceptibility (or lack of resistance) played an etiologic role. Lod score analysis based on nine families suggested a close association between such a gene (labeled MSS) and the HL-A gene complex. However, when all 10 available families were analyzed, the association approached but did not reach statistical significance. Thus, the HL-A haplotype segregation did not prove that a histocompatibility-linked gene is related to the cause of multiple sclerosis, but study of additional multiplex families is certainly warranted. Other factors, possibly genetic (although not HL-A-linked), environmental, or the two together, may be required for multiple sclerosis to become clinically apparent.


Diagnostic use of meternal serum alpha-fetoprotein levels. Alpha-fetoprotein (AFP) levels in human maternal serum were elevated in 14 patients when measured by a radioimmunoassay. In 8 patients the elveated serum levels of AFP correlated with increased concentration of AFP in amiotic fluid and were diagnostic of fetal defects. The elevated AFP levels in the remaining 6 patients were shown to be the result of fetomaternal transfusion from either amniocentesis or natural causes. Serum samples drawn after amniocentesis through an anterior placenta may show false-positive elevations. The use of both maternal serum and amniotic fluid samples in pregnancies at high risk for neural tube defects can decrease the risk of diagnostic errors due to mistakes in gestational datind and may increase the diagnostic sensitivity of amniocentesis.


Studies on cystic fibrosis using isoelectric focusing. II. Demonstration of deficient proteolytic cleavage of alpha2-macroglobulin in cystic fibrosis plasma. A protein with an isoelectric point (pI) of 5.48 was found to be deficient in plasma from most cystic fibrosis (CF) homozygotes and obligate heterozygote carriers of CF as compared with normal control plasma. Purification of the protein with a pI of 5.48 from normal plasma was performed using ammonium sulfate precipitation, DEAE-cellulose and CM-cellulose chromatography, Sephadex G-200- gel filtration, starch block electrophoresis, and Sepharose 4B gel filtration. The purified protein migrated as a single band on polyacrylamide gel electrophoresis, and displayed a single arc on immunoelectrophoresis against polyvalent antiserum to whole human serum. Results from various techniques used in its characterization indicate that this protein is a fragment of alpha2-macroglobulin (alpha2M) which is derived from alpha2M by proteolytic cleavage of intact alpha2M subunits. Quantitation of alpha2M levels in plasma indicated no significant differences between levels of alpha2M in CF homozygote, obligate heterozygote carrier, or normal control plasma samples. Quantitation of arginine esterase activity in plasma treated with cloroform and ellagic acid indicated that both the total arginine esterase activity and that fraction of arginine esterase activity inhibited by soybean trypsin inhibitor (SBTI) were decreased in most CF homozygote and obligate heterozygote plasma samples relative to normal control values. The results of this study indicate that plasma samples from CF homozygotes and obligate heterozygote carriers for CF show deficient proteolytic cleavage of alpha2M as compared with normal control plasma, and suggest that a structural abnormality in alpha2M or a deficiency in plasma proteolytic activity may be responsible for this deficiency in proteolysis.


Serum immunoglobulin E concentrations and radioallergosorbent tests in children with atopic dermatitis. Serum IgE concentrations and the presence of allergen-specific IgE were determined in a series of 23 children with atopic dermatitis. In this group 83% had significantly elevated serum levels of IgE, 91% had coexistent respiratory allergy, 70% had radioallergosorbent test (RAST) evidence of pollen hypersensitivity, and 43% gave a history and demonstrated a RAST score consistent with milk or egg hypersensitivity. In patients with eczema a significant proportion of the elevated serum IgE appears to be antigen specific.


Indium (111In)-labelled bleomycin for the detection of intracranial lesions. Brain scans with 99mTc pertechnetate were compared with scans made after administration of 111Indium bleomycin in 38 patients scanned on 41 occasions. They gave similar results in  34 pairs of examinations, including cases in which both failed to detect the tumour. In seven cases, the two agents differed. In two of these bleomycin distinguished residual tumour from the effects of craniotomy more clearly than did pertechnetate; in three bleomycin apparently detected tumour not seen with pertechnetate, and in two the differences may have been due to technical factors, or are unexplained.


[Cytochemical demonstration and characterization of acid mucopolysaccharides in normal granulocytic series]. Metachromatic granulations are seen in myeloblasts, promyelocytes, myelocytes, metamyelocytes and young mature cells, after staining by all metachromatic dyes, except methylene blue. Furthermore by screening at various pHs granular metachromasia is detectable starting at pH 3.2 in 6% of case, at pH 4 in 78% of cases, at pH 4.5 in 16% of cases. The use of toluidine blue 10(-4) M in solutions at varying pH, after methylation and after alkali demethylation demonstrate the acid sulfated mucopolysaccharide react within the pH range (3.2), 4, 4.5, 5; persistence of non-alcohol resistant granular metachromasia above pH 5.5 suggests the presence of granules containing acid mucopolysaccharides staining as the result of possessing --COOH radicals. This data was verified by other histochemical techniques (Alcian blue and PAS staining) which have shown positive granules. All the data on the metachromatic, alcian blue and PAS positive granulations, have been carefully confirmed by chemical and enzymatic reactions. The results of this study led us to the conclusion that azurophilic granulations are made of a sulfated polysaccharide of chondroitinsulfate group. In the more immature cells alcian blue positive granules (mucopolysaccharide of acid hyaluronic type) and PAS positive granules (polysaccharides with a low sulfation level) can be demonstrated. From this data, it is suggested that azurophilic granulations are the final event of an evolutive process of polysaccharide material, fundamentally based on a progressive sulfation.


[Acute mast-cell leukemia. Cytochemical and ultrastructural study, about a particular case (author's transl)]. A case of acute Mast-cell leukemia was studied. A 39 years old female presenting with a brief history of abdominal pain and attacks of flushing; peripheral blood and bone marrow contained up to 60% of poorly differentiated blasts with clumping of deep purpule granules. Peroxydase reaction stains were negative, chloroacetate esterase were strongly positive. Toluidine blue revealed metachromatic stain. Histamine content of the cells was highly greater than normal but nos heparinoid activity could be demonstrated. These abnormal mast-cells have been investigated with the electron microscope; only the dense particular type of granule substructure was found, without any lamellae component. The cells were temptatively classified as "immature" mast-cell. The disease was interpretated as an acute leukemic variety of systemic mastocytosis.


Appliances for cutaneous enterostomies.

Appliances for cutaneous enterostomies. This report deals with appliances for permanent cutaneous enterostomies such as ileostomy, colostomy and ileal-bladder (called ostomies below). The purpose of the report is to facilitate the choice of appliances for these types of ostomies for prescriber as well as the person operated.


Investigations on the biological activity of Tylopilus felleus (Bull. Ex Fr.) P. Karst. by means of phytobiological tests. The effect of the undialysed (ND) aqueous fraction prepared from the fruitbodies of Tylopilus felleus and of actinomycin C on the biosynthesis of DNA in the seedling roots of Triticum vulgare and on the increase of their mass was investigated. The content of DNA (expressed in mug) in the determined amount of the seedling roots of Triticum vulgare after treating of material with the ND fraction, was 9-1--23-3% higher than in the control. The investigated fraction inhibited the increase of the mass of seedling roots in the range 24-5--48-0%. It seems possible that ND fraction inhibits the biosynthesis of the other components of the cells, while the synthesis rate of DNA is only slightly changed. ND fraction and N-hydroxyurea inhibited the linear growth and the increase of the mass of Lepidium sativum roots in the test acc. to Gagiu et al. [5]. Using the Constantinescu et al. test[3,4] the CMA value of polysaccharide fractions was calculated. The pycnose phenomenon in the course of cytological analysis of the meristematic cells of the wheat root seedlings treated with polysaccharide fraction was observed.


Asymmetric orientation of a phage coat protein in cytoplasmic membrane of Escherichia coli. The coat protein of a filamentous phage (M13) enters the cytoplasmic membrane from two directions: from the outside upon infection and from the cell interior late in the viral life cycle prior to phage assembly and extrusion. Binding of 125I-labeled anti-coat protein antibody to spheroplasts or to inverted vesicles was used to assay the orientation of coat protein in the membrane. Both parental and newly synthesized coat protein were found to be exposed on the outer surface of the cytoplasmic membrane. Coat protein in intact infected cells is also accessible to external antibody. Thus two different processes of assembling a protein into membrane, each starting from a different membrane surface, appear to produce similar surface orientations.


Subunit structure, cell surface orientation, and partial amino-acid sequences of murine histocompatibility antigens. Detergent and papain solubilized murine histocompatibility (H-2) antigens have been compared by gel exclusion chromatography, ultracentrifugation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and amino-acid sequence analysis. From these data, we propose a molecular model for the H-2 antigens that includes the size and arrangement of the subunits on the cell surface and in solution, and we provide evidence for the orientation of these molecules on the cell surface. Detergent solubilized H-2 antigens (molecular weight 116,000) consist of two disulfide-linked heavy chains (46,000 daltons) and two monocovalently associated light chains (12,000 daltons). Alkylation with iodoacetamide prior to extraction prevented the formation of a disulfide linkage between the two heavy chains. A water-soluble 51,000-dalton molecule (Fs) consisting of a 39,000-dalton fragment (FH) of the heavy chain and one intact light chain was obtained by papain digestion of cells or detergent extracts. Therefore, the disulfide linkage between the heavy chains is located in the remaining membrane-associated portion (Fm). Amino-acid sequence analysis of the FH fragment of H-2Kb by radiochemical techniques showed that it is identical to the detergent solubilized H-2Kb heavy chain in eight positions for the three amino acids tested. These data indicate that the fragment FH derives from the amino-terminus of the heavy chain and suggest that it projects outward from the cell surface, while the carboxyl-terminal region is associated with the plasma membrane. The described amino-terminal sequence data have been found constant in H-2Kb, H-2Kd, H-2Kk, H-2Db, and H-2Dd gene products. These data support the hypothesis that the K and D products of the major histocompatibility antigen complex have evolved by gene duplication.


Radioimmunoassay of bovine heart protein kinase. Immunization of guinea pigs with bovine cardiac cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) resulted in the development of precipitating antibodies to the cAMP-binding subunit of the enzyme. Both the phosphorylated and nonphosphorylated cAMP-binding protein of the protein kinase reacted with the antiserum. A radioimmunoassay was developed that detects 10 ng of holoenzyme and permits measurement of enzyme concentrations in bovine cardiac muscle. Bovine liver, kidney, brain, and skeletal muscle contain protein kinases which are immunologically identical to those found in bovine cardiac muscle. However, the proportion of immuno-reactive enzyme activity differed for each tissue. All of the immunologically nonreactive enzyme in skeletal muscle and heart was separable from immunoreactive enzyme by chromatography on DEAE-cellulose. Rat tissues and pig heart contained protein kinase activity that crossreacted immunologically in a nonparallel fashion with bovine cardiac enzyme. These results indicate that cAMP-dependent protein kinases within and between species are immunologically heterogeneous.


Partial purification of a serum factor that causes necrosis of tumors. Tumor necrosis can be induced in transplanted mouse methylcholanthrene-induced sarcoma by a tumor necrosis factor in the serum of mice infected with bacillus Calmette-Guérin and given bacterial endotoxin. Sera from normal mice, endotoxin-treated mice, and mice infected with bacillus Calmette-Guérin do not contain this factor. A 20- to 30-fold purification of the serum factor has been achieved by (NH4)2SO4 fractionation, Sephadex G-100 and G-200 gel filtration, and preparative polyacrylamide electrophoresis. Tumor necrosis factor is not bacterial endotoxin. It migrates with alpha-globulins, is made up of at least four subunits, and has a molecular weight of about 150,000. The active factor is a glycoprotein that contains sialic acid and galactosamine.


Biochemistry of the filaments of brain.

Biochemistry of the filaments of brain. Intermediate filaments-cytoplasmic filaments with a diameter of 8-9 nm-have been described in a large variety of cell types. In this study, the subunit protein of the neurofilament and the presumptive subunit of the astroglial filament are compared by immunological and biochemical methods and are found to be very similar. Strong crossreactions are also found between these proteins in a variety of mammalian species. These results suggest that the intermediate filaments may, like microtubules and microfilaments, represent a highly conserved  and widely distributed fibrous protein system.


Mechanisms of adhesion among cells from neural tissues of the chick embryo. In order to analyze the molecular mechanisms of cell adhesion during development, proteins on the surface of chick embryonic neural cells were compared with proteins released after placing these cells in culture. One of the components released into culture, F1 (molecular weight, Mr 140,000), was derived by proteolytic cleavage of a cell surface precursor with a molecular weight of at least 240,000. Another protein, F2, recovered from culture as a dimer (Mr 1110,000), appeared to be a product of limited proteolytic cleavage of F1. Cells in retinal tissue possessed a surface protein of Mr 150,000 that also appeared to be derived by limited proteolytic cleavage of the cell surface precursor. Antibodies to F2 interacted with determinants on the cell surface protein of Mr 150,000, and specifically prevented homologous and heterologous binding among dissociated retinal and brain cells. In contrast, antibodies to F1 failed to prevent cell-cell adhesion and did not crossreact with F2. These data suggest that the cell surface protein of Mr 150,000 generated by limited proteolysis is involved in adhesion of both retinal and brain cells. Cell-cell binding of both retinal and brain cells varied as a function of developmental age and brain cells acquired their binding properties at an earlier time than retinal cells. Similar results were obtained in experiments on the binding of retinal and brain cells of different ages to nylon fibres coated with antibodies to F2. The results of the molecular and cellular experiments are incorporated in a model for cell adhesion invoking both proteolytic activation and modulation of cell surface ligands.


Structure and evolution of transplantation antigens: partial amino-acid sequences of H-2K and H-2D alloantigens. Techniques for the amino acid sequence analysis of subnanomole quantities of polypeptides have been applied to characterize beta2-microglobulin and transplantation antigens of the mouse isolated from spleen cells by indirect immunoprecipitation. Eleven residues were identified throughout the NH2-terminal 27 residues of the beta2-microglobulin; all were identical to residues seen at the corresponding positions of beta2-microglobulins from other species. Two K and two D transplantation antigens were examined and the following generalizations emerged from the limited partial amino-acid sequence data: (1) the K and D molecules are homologous to one another; (2) they do not show amino acid sequence homology with immunoglobulins; (3) the two K and two D molecules differ from one another by multiple amino acid substitutions; and (4) the K molecules as a class cannot be distinguished from the D molecules as a class. The genetic and evolutionary implications of these observations are discussed.


A molecular concept of the properdin pathway. The sequential events of the properdin system were analyzed. Properdin-depleted serum allows the formation of a Factor B- and D-dependent C3 convertase. This enzyme, called the properdin-receptor-forming enzyme, was shown to utilize a novel serum component, the initiating factor. The protein is a beta-globulin in precursor form and is distinct from immunoglobulins. The function of the enzyme is to deposit C3b on the surface of activator particles. Apparently doublets of C3b are required for the formation of the properdin-activating principle. It consists of a complex containing surface-bound C3b and activated Factor B. properdin precursor is activated by binding to this complex without detectable change in molecular weight. The transition of properdin precursor to activated properdin is probably caused by a conformational change. The complex, consisting of bound C3b, properdin, and activated Factor B, represents the enzyme that acts on C5, thereby initiating self-assembly of the membrane attack system. Native C3 is not needed for the function of the enzyme. It is disassembled by soluble C3 or C3b and its formation is under the control of the properdin-receptor-destroying enzyme, which may be identical with the C3b inactivator.


A new protein with a particular thermoprecipitability in bovine milk. A new protein with a particular thermoprecipitability was isolated from bovine milk and tentatively termed milk pyroglobulin. The protein which was soluble at a relatively cold temperature was precipitated by raising the temperature to a certain degree depending on the concentration of the protein. The precipitate disappeared on recooling. This protein had the electrophoretic mobility of gamma globulin but did not carry either antigenic specificities of immunoglobulins or of free secretory component. The molecular weight was estimated to be approximately 60,000 in thin-layer gel filtration on Sephadex G-200 superfine gel, but the protein appeared to be convertible to molecules with a lower molecular weight of approximately 20,000 in the presence of bovine serum albumin. The presence of the albumin inhibited the thermoprecipitation as did alpha-lactalbumin but not IgG immunoglobulin from bovine colostrum. In SDS-polyacrylamide gel electrophoresis, the protein was separated into two components having a molecular weight of 19,000 and 10,000, respectively. Both components were thermoprecipitable and carried identical antigenic determinants.


Cordycepin inhibition of 3-methylcholanthrene-induced transformation in vitro. Cordycepin (3-deoxyadenosine), an inhibitor of poly (a) synthesis, was found to inhibit the induction of the endogenous type "C" RNA virus by 5-iodo-2'-deoxyuridine in a line of Fisher rat embryo cells (H43) grown in vitro, and when continuously incorporated into the medium at those same concentrations, it was found to protect the cells from transformation by the chemical carcinogen 3-methylcholanthrene.


Radioimmunoassay of beta2-microglobulin. A radioimmunoassay for quantitation of beta2-microglobulin in serum and urine is described. Polyethylene glycol 6000 was used to precipitate the antigen-antibody complex. The assay can be performed within 5 hr. In healthy human subjects (mean age, 30.6 years and 42.0 years for serum and urine determinations, respectively) the mean concentration of beta2-microglobulin in serum was 125 nmol/l (range, 49-190 nmol/l). In men the mean 24-hr urinary excretion was 12.9 nmol (range, 8.6-19.2 nmol), and in women it was 5.5 nmol (range, 2.9-8.7 nmol). The assay range was 0.23-19.40 nmol/l, and the detection limit was 0.042 nmol/l, using a prolonged incubation time. The coefficient of variation based on 20 determinations in serum dilutions with a concentration of beta2-microglobulin of 8.14 and 1.92 nmol/l was 8.1 per cent and 9.0 per cent, respectively.


Cationic proteins of human granulocytes. V. Interaction with plasma protease inhibitors. Several cationic proteins of human granulocytes possess chymotrypsin-like and bactericidal activities. The heat-labile chymotrypsin-like activity is inhibited by serum, owing to complex formation with alpha2-macroglobulin and alpha1-antitrypsin. The molar affinity of the cationic proteins for alpha2-macroglobulin is much higher than that for alpha1-antitrypsin. The results indicate that the molar combining ratios are 1:1 for cationic protein to alpha1-antitrypsin and 2:1 for cationic protein to alpha2-macroglobulin. The proteolytic activity against fibrinogen and casein is inhibited by both alpha2-macroglobulin and alpha1-antitrypsin, whereas the activity against small molecular synthetic substrates is inhibited by alpha1-antitrypsin but not alpha2-macroglobulin. The heat-stable bactericidal action of the cationic proteins against Staphylococcus was also inhibited by serum, probably owing to complex formation with alpha2-macroglobulin and alpha1-antitrypsin.


Weight loss of prostatic tissue during electroresection. During electroresection the weight loss of prostatic tissue was demonstrated to vary between 15 and 42% with a mean value of 26%. Using a scalpel the mean weight loss was 12%.


Urethrocystography during and after transurethral prostatic resection. Ten men were subjected to transurethral electroresection because of prostatic adenoma. All were examined with urethrocystography on 3 occasions, viz. at the end of operation, 4-7 days later and after a further 2-3 months. Peroperative examination for residual adenoma appeared to be of little value, while examination a few days after the operation revealed residual adenomas in 2 cases and possibly also in a third. The cavity left after the operation had the same size at the peroperative and the first postoperative examination, though its outline was sometimes smoother at the latter. During urination the cavity invariably increased in size. At the second postoperative examination the operation cavity was clearly smaller and its outline smoother in 9 of 10 cases. The cavity still expanded during micturition. No passage of contrast medium to the veins was ever demonstrable. At the peroperative examination the contrast medium was not injected under any substantial pressure and the cavity was not exposed to pressure by micturition. Even at the first postoperative examination, when the operation cavity was exposed to pressure by urination, the veins that had been opened at operation had closed so effectively that no contrast medium passed outside the prostatic capsule. Urethrocystography in association with TUR of prostatic adenoma is of interest to the urological surgeon. It provides him with a possibility to check his work very carefully.


Management of thrombo-embolism after aortic valve replacement with the Björk-Shiley tilting disc valve. Medicamental prevention with dicumarol in comparison with dipyridamole - acetylsalicylic acid. Surgical treatment of prosthetic thrombosis. Dicumarol anticoagulation poved very effective in the prevention of thromboembolic complications after aortic valve replacement with the Björk-Shiley tilting disc valve. We have, however, encountered six late deaths because of massive cerebral hemorrhage, which represent 3% of the patients who were maintained on dicumarol medication at that time. This unacceptable mortality prompted us to introduce two programmes, one without anticoagulation and another one with dipyridamole-acetylsalicylic acid. Furthermore, dicumarol was terminated in patients with haemorrhagic episodes, instable anticoagulation, pregnancy, and in those reguiring surgery. The results were disappointing, however, and the majority of the patients involved were therefore put on dicumarol medication. Eleven of the 64 consecutive patients taking dipyridamole - acetylsalicylic acid had thrombo-embolic episodes during a mean follow-up period of 9 months...


Tracing axons and axon collaterals of spinal neurons using intracellular injection of horseradish peroxidase. Intracellular injection and subsequent histochemical localization of horseradish peroxidase have been used to stain the soma, dendrites, axons, and axon collaterals of spinalcervical tract neurons and unidentified dorsal horn neurons in the cat. This technique may be used in combination with the intracellular injection of Procion yellow to demonstrate by light microscopy connections between physiologically typed vertebrate neurons.


Radionuclide joint imaging.

Radionuclide joint imaging. Modern radionuclide techniques of joint imaging involve the use of either 99mTc-pertechnetate or 99mTc-phosphate compounds in conjunction with the Anger camera. In general, images obtained with both types of radiocompound are nonspecific--although increased uptake of 99mTc-pertechnetate usually denotes the presence of synovitis. The most popular uses of the technique are in documenting the extent and severity of inflammatory joint disease, assessing the effect of therapy, and establishing the diagnoses of Legg-Perthes disease and septic arthritis. The method is also useful in judging the extent of involvement in osteoarthritis of the knee prior to surgical intervention. Radionuclide joint imaging is more sensitive than clinical or radiographic techniques in detecting early joint involvement but usually it must be supplemented by other techniques to establish a specific diagnosis.


The anti-arrhythmic effects of perhexiline maleate in patients with ischaemic heart disease. In a preliminary study which lasted 14 weeks, an anti-anginal preparation, perhexiline maleate (Pexid), was prescribed in a dosage of 200 mg twice a day to 7 patients who were suffering from cardiac arrhythmias associated with ischaemic heart disease. There was a significant reduction in ventricular extrasystoles during the 4th and 8th weeks of the study in 6 of the patients who had multiple ventricular ectopic beats. In 4 of these patients, an effective anti-arrhythmic response was maintained until the end of the study. These findings confirm other studies regarding the efficacy of the preparation in reducing ventricular extrasystoles in patients with cardiac ischaemia.


Negative staining of rat tail tendon collagen fibrils with uranyl formate. Negative staining of rat tail tendon collagen fibrils with uranyl formate appears to reveal more detail in the axial banding pattern than any other positive or negative staining method hitherto employed. In addition, uranyl formate and other uranyl solutions appear to reveal fine, closely spaced, longitudinal filaments which may represent the individual tropocollagen molecules.


The histological localization of DNA in rabbit medullary neurons. The nuclei of unfixed isolated rabbit neurons cleared on incubation with DNAse (10 mg/ml), but not RNAse (10 mg/ml). The nuclei stained for DNA with eight chromosomal or nuclear stains more intensely than the cytoplasm, and less intensely after treatment with DNAse (10 mg/ml). On the other hand, when the whole tissue was embedded and sectioned, DNA did not appear to be stained in the nucleus; the nucleolus and the cytoplasm were more heavily stained than the nucleoplasm. Possible explanations for this apparent anomaly are considered. It was concluded that DNA diffused out of the nucleus during embedding and sectioning, and that the colouration of the nucleolus and cytoplasm with the eight staining systems used was due to other nucleotides present.


On the chemical basis of chromosome banding patterns. A comparative study of the staining characteristics of four reagents for human chromosomes has been carried out. The four reagents are: (I) quinacrine mustard, as an alkylating agent, (II) the dihydroxy derivative of quinacrine mustard, (III) quinacrine, and (IV) 9-amino-6-chloro-2-methoxyacridine. The last reagent does not possess the amino substituted side chain even though it has the same intercalating nucleus. Comparison of the first three compounds in their staining and banding behavior suggested the initial step leading to banding may be the displacement of the nucleoprotein sites in hcromosomes. The Q and G banding could be blocked experimentally by treating the chromosome preparation with dimethylamine solution. This result may suggest that these sites have weaker basic proteins (nonhistone proteins?). The use of compound IV, which does not have the side chain in the molecule but does have the same intercalating chromophore, did not lead to banding and gives indirect support to this hypothesis. A combined use of compound IV and quinacrine may be useful for the determination of total DNA vs. banding DNA.


Elimination of precipitates in oil red O fat stain by adding dextrin. Addition of dextrin in the final 60% isopropanol of the Lillie-Ashburn super-saturated oil red O isopropanol technic moderately intensified the stain and decreased our required staining interval. Precipitates were decreased and the diluted solution remained usable into the second week. A saturated 60% isopropanol oil red O solution contained 33 mg/100 ml. Without dextrin the fresh supersaturated solution contains 40 mg, after 3 days 25 mg. With dextrin the fresh solution contained 130 mg dye, the 10-day-old one 100 mg/100 ml.


Influence of light and mounting medium on the fading of Feulgen stain. Serial microspectrophotometric estimations of the absorbance of Feulgen-stained interphase nuclei of human fibroblasts were made on slides mounted in a variety of mounting media and stored in light or in darkness. All preparations showed some fading, at rates which varied with different mountants, were greater in the light than in the dark, and were greater in the monochromatic illumination of the microspectrophotometer under working conditions than in normal laboratory light conditions. Fading was minimised by using XAM improved white neutral mounting medium (G.T. Gurr), storing slides in darkenss, and by reading samples as quickly as possible.


The use of a basic dye (azure A or toluidine blue) plus a cationic surfactant for selective staining of RNA: a technical and mechanistic study. Selective purple staining of RNA-rich structures such as basophilic cytoplasms of exocrine pancreas and plasma cells, Nissl substance, and nucleoli was achieved by treating tissue sections as follows. Stain dewaxed sections for 1/2 hour in a dyebath containing 0.1% w/v axure A or toluidine blue and 1% cationic surfactant (Hyamine 2389, a 50% w/v aqueous solution of diisobutylphenoxyethoxyethyldimethylbenzylammonium chloride; or benzyldimethylammonium chloride, or cetylpyridinium bromide, or cetyltrimethylammonium bromide) buffered to pH 7 with phosphate. Rinse in water, blot, air dry and mount in synthetic resin. Intense purple staining of RNA-rich regions occurred after fixation in neutral formalin or in Carnoy's or Gendre's fluids, though satisfactory results were also found after fixation in acetone or alcohol. Chromatin generally stained a very pale azure after all fixations, though occasionally nuclei were unstained (Gendre's or Zenker's fluids). Subjecting tissue sections to acid hydrolysis or to digestion by RNAase eliminated or reduced the purple staining, but left the azure staining of nuclei unaffected. Satisfactory staining of RNA-rich structures was not critically dependent on the precise concentrations of dye, surfactant or inorganic salts in the dyebath, nor on pH, staining time or chemical nature of the surfactant. The staining patterns can be rationalized with a tissue model that considers both surface charge and permeability factors, since present in the dyebath are small dye cations and large cationic surfactant micelles. As micelles and dye will both quickly penetrate basophilic structures considered to be porous, such as chromatin, competition will then greatly reduce staining of such substrates. But the large micelles will only slowly penetrate regions considered to be more impermeable, such as basophilic cytoplasms, so consequently small fast moving dye ions may enter and stain without competition.


Vanillin-hydrochloric acid as a histochemical test for tannin. Condensed tannin (leucoanthocyanins and catechins) can be demonstrated in fresh plant sections with saturated alcoholic vanillin followed by addition of concentrated HCl. Bright red vanillin-tannin condensates are formed immediately. Preparations may then be made permanent by mounting in a 1:1 mixture of Hoyer's medium and concentrated HCl. Some fading and loss of tannin occurs. The phloroglucinol-HCl test for lignin can also be made permanent with this acidic mountant.


The use of an optical brightener in the study of plant structure. An optical brightener Calcoflour White M2R New has been used to stain cell walls of higher plants. It can be used either as a vital stain for intact plants or for hand sections and plastic-embedded thin sections. Walls are brilliantly fluorescent while most cytoplasmic components are normally unstained. The brightener binds strongly to cellulose, carboxylated polysaccharides, and callose. Staining for 20 sec to 2 min in a 0.01% solution of the brightener is preferred for most purposes.


Cytogenetics analysis of meiotic chromosomes of irradiated mice and their progeny after treatment with streptomycin and dihydrodeoxystreptomycin. The purpose of this investigation is to find out whether streptomycin and the related compound dihydrodeoxystreptomycin have any mutagenic effect and whether they both are capable of recovering X-ray induced chromosomal translocations in mouse spermatogonia of directly treated animals and their progeny of the first generation. The cytological findings show the absence of any mutagenic effect in animals nonirradiated and treated with streptomycin and dihydrodeoxystreptomycin. The frequency of chromosomal translocation after total irradiation was 9,07%; in animals treated with streptomycin following irradiation 5.13%, and in those irradiated and treated with dihyrodeoxystreptomycin, 3.70%. Male offsprings, originated from parents treated only with antibiotics show no chromosomal translocations. However, offsprings originated from irradiated and treated parents gave birth to the male offspring with chromosomal translocations.


Biological activity of some steroidal compounds in the adult and larval frogs. Four steroids were tested for their biological activity, using the sex-steroid-dependent redevelopment of the secondary sex characteristics in adult frogs and gonadal sex differentiation in larval frogs as end points. In adult frogs, 19-norprogesterone and 6-chloro-17alpha-hydroxy-4, 6-pregnadiene-3,20-dione had antiandrogenic and antiestrogenic effects. 2alpha, 17alpha-Dimethyl-DHT and 2alpha-methyl-DHT were potent androgens and effective antiestrogens. In the larval frogs, all four compounds had a masculinizing effect upon the undifferentiated gonads.


Radioimmune assay of heterologous serum gamma-globulin in patients receiving rabbit antihuman thymocyte globulin. A radioimmune assay (RIA) method for detecting heterologous serum rabbit gamma-globulin (RG) and antibody to this protein is described. The methodology is used for monitoring serum levels of rabbit globulin in patients receiving rabbit ATG (RATG). In 7 cardiac recipients receiving RATG, maximum serum levels of RG were achieved 1-3 days after administration of final dose. RG half-life subsequent to peak serum levels was rapid (X = 36 hr) in 4 patients and prolonged (X = 18 days) in 3 patients. Patient antibody to rabbit gamma-globulin was detectable only in those patients with short RG half-life. Antirabbit antibody titers in these patients were extremely low and barely detectable by RIA.


Cross reactivity between H-2K and H-2D products. II. Identification of the cross reacting specificities. Absorption analyses were conducted on antisera which had previously been shown to detect cross reactivity between the H-2K and H-2D gene products. These analyses revealed that the cross reactions were due to known public H-2 specificities. Identification of cross reactive anti-H-2.3 and anti H-2.5 antibodies confirmed earlier predictions that genes controlling these specificities should be localized at opposite ends of the H-2 complex. The finding of H-2.29 activity on both sides of the S region clarified ambiguities encountered in assigning this specificity to certain recombinant types. Results with H-2.36 support the suggestion that this determinant may also be specified by both H-2K and H-2D genes.


Primary antibody response against K and D regions of the H-2a and H-2d haplotypes. The capacity of D and K antigens of the H-2d and H-2a haplotypes to induce primary IgM response was evaluated in host-donor combinations using congenic recombinant strains of mice. Host animals were immunized with an i.p. injection of 2 X 10(7) allogeneic spleen cells. Direct plaque-forming cells appearing in immune spleens were assayed with cells of lymphomas L2 of strain A and L5178Y of strain DBA/2, and mastocytoma P815 of strain DBA/2, as targets. Serum antibodies were titrated for cytolytic activity with the same targets as above, and with spleen cells of strain A mice. Titration of serum hemagglutinins was performed using A erythrocytes. The following results were obtained: (1) H-2Dd antigens were shown to be more potent in stimulating primary IgM antibody response than were H-2Kk and H-2Kd antigens, as measured by both plaque assay and serum antibody titration. (2) The observed dominance of D antigens of the haplotypes under study did not seem to be dependent on the number of antigenic specificities involved. (3) Comparable results were obtained with both lymphoid and nonlymphoid target cells of either normal or malignant origin.


Antibody response after single dose human alloimmunization. Six individuals were immunized once, intradermally, with buffy coat cells from 100 ml of whole blood. The donor differed from the recipient for four HL-A antigens, two from the first and two from the second series. Two of the six recipients developed complement dependent cytotoxic antibodies, one of them against the immunizing donor only. Four of the six developed antibodies which were able to induce cell-mediated cytotoxicity, and which also inhibited the mixed lymphocyte culture interaction. Manily the responding cell in mixed lymphocyte culture was found to be inhibited. Antibodies with HL-A specificity seemed, at least partly, to be responsible for the observed effects.


Nonhormonal chemotherapy for disseminated renal cell carcinoma. Twenty-five patients with disseminated renal cell carcinoma have been followed for eleven months. These patients have been treated with CCNU, bleomycin, methotrexate, and platinum in various combinations. The results have been discussed in light of other studies using chemotherapeutic agents against this disease process.


Natural history of benign prostatic hypertrophy and acute urinary retention. Twenty-six patients with prostatism due to benign prostatic hypertrophy were evaluated prospectively every three to six months for three years. Using both subjective and objective criteria significant deterioration was demonstrated. The rate of deterioration appeared independent of prostatic size. In the individual patient progression was variable. More than half of the patients were unchanged or improved after two years. Acute urinary retention appeared independent of the degree of prostatism and therefore unpredictable. The methods can be used to evaluate medical treatments of benign prostatic hypertrophy.


Prostatic antibacterial factor. Identity and significance. Normal human prostatic fluid possesses pronounced antibacterial activity. This activity is absent or markedly diminished in the fluid of men with chronic bacterial prostatitis. Ion-probe and mass spectrographic analysis of this antibacterial factor has shown it to be a zinc salt. Prostatic fluid zinc levels in 15 men with chronic bacterial prostatitis averaged 50 mug. per milliliter (range 0 to 139 mug. per milliliter). The zinc level in the expressed prostate secretion (EPS) of 49 control men averaged 448 mug. per milliliter (range 150 to 1,000 mug. per milliliter). There was no overlap in the range of zinc values between the two groups. The decrease in EPS zinc concentration in the patient population was not secondary to a decreased serum zinc level. Exogenous zinc given orally did not increase the EPS zinc level. The decrease in EPS zinc was not limited to infected prostatic fluid cultures and may precede the entry of bacteria into the prostate. The data presented suggest that zinc may serve as an in vivo defense mechanism against prostatic invasion and subsequent urinary tract infections in men.


[Swelling and contraction of rat liver mitochondria under the effect of hexachlorocyclohexane gamma-isomer and polychlorocamphene]. Swelling and contraction of the rat liver mitochondria were studied as affected by chloroorganic pesticides of hexachlorocyclohexane gamma-isomer (gamma-HCCH) and polychlorocamphene (PCC). Administration for two days of gamma-HCCH in a dose of 34 mg/kg and PCC in a dose of 48 mg/kg established to ccause swelling of the liver mitochindria in vivo, a decrease in their ability to swelling in KCl and KH2PO4 and to contraction with addition of ATP. When gamma-HCCH is administered daily for six months in a dose of 1.7 mg/kg the indices under study rise and in case of PCC analogous adninistration in a dose of 2.4 mg/kg-- the drop. The found differince in the effect of the mentioned preparations when they are introduced to the animal organism for a long time might be connected with singularities in their cumulative properties.


[Method of determination of fat deposit in chickens]. The method described is based on the histochemical demonstration of fats with the use of Sudan stains and the clearing of tissues in an alkaline medium. It is employed to investigate whole birds, thick sections or individual organs to determine the morphotopographic localization of the fat depots. The procedure comprises the alcohol fixation of tissues, the staining of lipids with Sudan black, the clearing of tissues in a solution of potassium hydroxide, and the final mounting of the cleared materials in glycerine. This treatment results in that the sites of fat deposition assume a blue coloration, the bones are grey, and all remaining tissues and organs (if properly bled) are colorless and transparent. The method can also be successfully used with materials that have been preliminary fixed with formalin but their clearing has been considerably worse.


The effect of bleomycin on rapidly proliferating epidermis. A comparative investigation using micro-flow fluorometry, H3Tdr incorporation and a stathmokinetic method (colcemid). At different time intervals after injection of Bleomycin (BLM) th effect on several kinetic parameters of the hairless mouse epidermis stimulated to proliferate by previous adhesive tape stripping was measured. Micro-flow fluorometry was used to determine the relative number of cells in the various phases of the cell cycle (G1, S and G2). Tritiated thymidine was used to determine labelling indices and grain counts. Colcemid was used to observe the mitotic rate. An initial decrease followed by a subsequent significant increase compared to the non-BLM-treated controls was observed in all parameters studied except the mitotic rate, which remained lower than in the control animals during all 48 hours. The transit time of the cells through the S-phase was initially slightly prolonged, but thereafter it seemed to be shorter than that of the controls. BLM seems to provoke a partial blocking of cells in the G1 phase. When the block is released, a greater number of cells pass through the S phase in partial synchrony at a higher than normal speed. BLM induced a low mitotic rate which remained below the level of that of the normal animals after stripping, even though there obviously was a considerably higher influx of cells from the S phase to the G2 phase. This resulted in a subsequent accumulation of cells in the G2-phase. Thus, BLM has also a blocking effect on the G2-M boundary of the cell cycle. This inhibitory effect of BLM on the mitotic rate was shown to be independent of the effect of BLM on the DNA synthesis. BLM therefore seems to have complex influence on epidermal cell kinetics in vivo. Cells in G1-phase are partially and transiently blocked, but this block is soon released. These cells thereafter pass through the S-phase and pile up in the G2-phase, because BLM also blocks the passage of cells from the G2-phase to mitosis. The overall reduction in cell proliferation seen after BLM in vivo seems mainly to be due to the effect on the G2-M boundray of the cell cycle.


[Esophago-intestinal bypass anastomoses for inoperable cancer of the proximal portion of the stomach and abdominal portion of the esophagus]. To lessen a damage and to eliminate the reflux-esophagitis in bypass anastomoses, constructed for inoperable cancer of the stomach and epicardia, it is suggested to create a side-to side enteroesophageal anastomosis by means of an apparatus of the authors' design. The anastomosis is constructed above the tumor via a transperitoneal approach. To prevent regurgitation of the intestinal juice in the esophagus an invagination-valve enteroanastomosis elaborated at the clinic was employed. The immediate results are good.


[Possibilities for the spread of alpha-fetoprotein and heterologous antibodies in mother and fetus during transplacental carcinogenesis]. The study of distribution of J125 labelled homologous alpha-fetoproteins (AFP) and heterologous antibodies (anti-AFP) in rats indicated some differences in the level of radioactivity of organs and tissues in animals, depending on age, especially in kidneys and large intestine. In normal pregnancy AFP passes through the placenta in both directions, but in rather less relative amounts from the fetus to mother. No labelled AFP was found in the amniotic fluid of fetuses 5 hours after its injection to pregnant mice. Anti-ATP injected in normal pregnant mice failed to pass through the placental barrier to the fetus, and radioactivity 5 hours following the injection was detected neither in fetal tissues nor in the amniotic fluid. After transplacental exposure of fetuses to methyl nitrosurea the labelled AFP was found in the amniotic fluid, while anti-AFP-both in fetal tissues and the amniotic fluid.


[Metabolism of histamine in patients with coronary atherosclerosis]. In patients with coronary atherosclerosis in I and III stages content of histamine in blood, excretion of free histamine with urine, activities of serum histidine decarboxylase and diaminooxidase, histaminopexy of blood serum and content of antihistamine factor were studied. In patients with the disease of the I stage during the attacks of stenocardia content of histamine in blood, the activity of diaminooxidase and content of degranulated basophils were increased, but the histidine decarboxylase activity, histaminopexy, content of antihistamine factor and excretion of free histamine with urine were normal. During the stenocardia attacks in patients with coronary atherosclerosis of the III stage content of degranulated basophils, the histidine decarboxylase activity were increased, histaminopexy and titres of antihistamine factor were decreased. Between the content of histamine in blood and the diaminooxidase activity no correlation was observed. This lack of correlation could cause development of hyperhistaminaemia and increased excretion of free histamine with urine. Antihistamine and desensitizing preparations (pipolphen, heparin, amidopyrine and ascorbic acid) increased the therapeutic efficiency of vasodilating drugs, decreased stenocardia attacks, accelerated both clinical improvement and normalization of histamine metabolism.


[Hygienic standards for hydroxymethylfurfural in food products]. The effect of a long-term peroral introduction of oxymethylfurfurol on the organism of albino rats was studied. The compound was administered to rats via a tube 6 days in a week for 11 months in doses of 40, 80 and 160 mg/kg with controls receiving water in place of the oxymethylfurfurol. The rats receiving 160 mg of oxymethylfurfurol per kg of body weight demonstrated a temporary rise in the level of gamma-globulin in the blood serum, an increase in the relative weight of the spleen, a tendency towards a greater activity of tributyrinase in the hepatic tissue. Dases of 40 and 80 mg/kg did not affect the protein and lipids metabolism characteristics under study, the suprarenal content of ascorbic acid, the activity of the liver succinate-dehydrogenase, the morphological structure of the internal organs, nor the general condition and dynamic changes in the weight of the animals. From the results obtained it follows that the possibility of any toxic action of oxymethylfurfurol on the albino rats with its peroral administration in a dose of 80 mg/kg and below is ruled out. By adopting a 40-fold safety margin the acceptable daily intake (ADI) of oxymethylfurfurol with food of man is estimated at up to 2 mg/kg of body weight.


[Changes in the serum protein fractions of pigeons in experimentally reproduced food toxinfection]. Paper electrophoresis was employed to analyze changes taking place in the composition of the blood serum protein fractions of pigeons following an experimental reproduction in them of toxinfection caused by Cl. perfringens, type A, and also upon exposure of the pigeons to a high and low temperature, as factors conducive to the development of toxinfection. The blood serum protein fractions of the diseased birds showed a distinct increase of the gamma-globulin fractions by as much as 4 times) that occurred at the expense of a corresponding drop of other globulin fractions, whereas the amount of albumin remained nearly the same. The action on the pigeons of high and low temperature also led to a change in the proportion of the protein fractions in their blood, the nature of these changes with the birds subjected to heating being similar to the changes occurring in developing toxinfection, whereas with the pigeons undergoing cooling the quantity of gamma-globulins increased at the expense of the albumins (the A/G ratio being almost halved).


[Study of the nature of the antigens detectable in antiserum cross reactions to the milk antigens of patients with breast carcinoma and to the type D oncornavirus isolated from HEp-2 cells (author's transl)]. Antigens of milk from normal women and from patients with mammary gland carcinoma and antigens of D type virus from HEp-2 cells were studied by means of microprecipitation in the gel and indirect immunofluorecence tests. An antiserum to HEp2 virus precipitated antigens of some milk specimens from cancer patients. However their virus precipitated antigens of some milk specimens from cancer patients. However their precipitation line was not identical to that of the test-system for group-specific antigens and the antiserum to HE-2 virus detected an antigen localized in the cytoplasm in the following cells: HEp-2, continuous cell lines and imprints of human mammary gland cancer, and epithelial cells from milk of patients with mammary gland carcinoma and from milk of normal women. The antiserum for the antigen of milk from cancer patients absorbed with HEp-2 cell homogenate lost its activity in the IF test. The nature of the detected antigens is discussed.


[Age profile of the antihemagglutinins and antineuraminidase antibodies in type A influenza (author's transl)]. Antineuraminidase and antihemagglutinating antibody studies were carried out in parallel in sera from subjects born in Bulgaria in 1968-1972, 1956-1960, 1946-1950, 1925-1935 and 1917-1920. It was found that the amount of both antineuraminidase and antihemagglutinating antibody in sera from normal subjects could vary depending upon the year of birth and the strain used for the test. The antibody spectrum was most narrow in children under 4 and wider in subjects born before 1925. Serograms of the age distribution of antineuraminidase antibody were different in 4 out of 5 strains used which confirmed the hypothesis of Francis and Davenport of the more solid immunological response to the first exposure to virus. Parallel examinations of the antibody spectrum in human sera confirmed differences in the antigenic specificity of the "active center" of neuraminidases of A/Hong Kong/1/68 (H3N2) and A/Singapore/1/57 (H2N2) viruses and for the first time provided evidence attesting to the existence of similar strain differences in neuraminidases belonging to the N1 group. Examinations for antineuraminidase antibody in addition to antihemagglutinins increase the effectiveness of evaluation of the immunological structure of the population.


[Study of the antigenic relationship of different strains of the rabies group viruses]. In neutralization tests in animals close antigenic relationship between human virus of acute encephalomyelitis (AEM) and viruses (297  and 598 SG strains) isolated from wild rodents in Czechoslovakia was first established. At the same time, poor antigenic relationship of human AEM virus to viruses isolated in Africa from bats (Lagos bat) and from shrews (YbAn 27377) was demonstrated. Certain differences in the antigenic properties of viruses isolated in Africa and in Czechoslovakia were found. These studies indicate the existence of many varieties in the rabies virus group. Ferther accumulation of data concerning different viruses of the rabies group is necessary as they may be helpful for elucidation of the pathology of certain neuroinfections due to viruses of this group as well as for creation of the necessary collection of the investigated strains for preparation of rabies vaccines.


[Autoimmune diseases - immunological bases]. Autosensibilisations are essentially more frequent than hitherto was assumed. They, in the main, can be led back to 3 basic mechanisms: 1. Autosensibilisations by determination of the antibodies, where no immunotolerance was present, 2. fraction of the immunotolerance by antibodies (e. g. due to cross-reactions or adjuvant effects), 3. fraction of the immunotolerance by primary changes of immunocompetent cells (e. g. lymphoproliferation diseases). Even the natural immunotolerance is possibly maintained by enhancement effects of blocking autoantibodies. Pathogenic effects (auto-immune diseases) are above all to be expected, if the autoantibodies or by endogenic substances sensibilised T-lymphocytes may react with the antigen and these immune reactions lead to lesions of cells or other structures. Finally for the progression is also necessary the persistence and the autonomisation of the autosensibilisation. Finally is discussed in which range the criteria for the diagnostics of an auto-immune disease derived by Milgrom and Witebsky from the animal experiment may be transposed to the clinic.


[Detection of specific antigen in the white blood cells of cattle with leukemia by a direct fluorescent antibody method (author's transl)]. The direct fluorescent antibody technique was used for detection of "specific" antigen in leukocytes of cattle with different forms of leukomia. Using fluorescein isothicoyanate-labeled immunoglobulins from colosterum of cows hyperimmunized with leukocyte mass from cattle with acute leukemia (hemocytobastosis), the "specific" antigen was detected in the cytoplasm of lymphoid and myeloid cells of animals with this and other forms of leukemia. This antigen was not detected in nuclear cells of the peripheral blood wither in normal animals or in animals with non-leukemic diseases (brucellosis, tuberculosis, various helminthic diseases) accompained by qualitative and quantitative changes in the blood similar to those leukemia.


[Determination of arbovirus group affiliation in the indirect hemagglutination reaction]. A dry polyvalent erythrocyte immunoglobulin diagnostic preparation for arboviruses of Group B may be prepared to be used in the indirect hemagglutination test. The preparation detects antigens of arboviruses of this group in the tissue culture fluid and in suckling mouse brain tissue treated with sucrose-acetone. The test with Group B arbovirus antigens is inhibited specifically by the homologous polyvalent immune gamma globulin. Inhibition of hemagglutination by species-specific immune globulins to individual members of Group B arboviruses permits typing of tick-borne encephalitis birus only. In making the erythrocyte diagnostic preparation, the optimal concentration of the sensitizing immune gamma globulin should be determined experimentally.


[Diagnostic staged program in thyroid diseases]. After some physiological principal remarks the modern possibilities of the in-vitro-diagnostics specific for the thyroid gland are briefly explained. The essential factors of disturbance which are necessary for the avoidance of false interpretations are mentioned. From the sequence of the description (BEJ, T4-test, T3-test, FT4-index, RIA-T3 and RIA-TSH) results the diagnostic step programme proposed by us, by means of which the majority of the functional disturbances of the thyroid gland existing may certainly be classified. Only after exhaustion of the in-vitro-diagnostics the radio-iodine-test should be performed.


[Alpha-fetoprotein: its significance in the monitoring of "at risk" pregnancies (author's transl)]. Having plotted a curve showing the normal values of Alpha-Foeto-protein (AFP) concentration in maternal serum and amniotic fluid, its significance in the monitoring of "at risk" pregnancies was examined and critically judged in the light of statements found in the literature. According to the results gained AFP determination in maternal serum or amniotic fluid can only be used with reservation as a monitoring test in "at risk" pregnancies. In particular in Rhesus Incompatibility it was impossible to establish the degree of foetal Haemolysis or to determine the best time for premature induction. In addition an intra-uterine death could not be predicted with certainty.


[Results of a follow up study of small for date babies. I. Physical development (author's transl)]. 74 small for date babies were investigated at the age of 10 years. The first part of the paper deals with the children's physical development and state of health. An attempt to correlate the degree of intrauterine malnutrition and postnatal development was made taking into account possible etiological factors, genetic, pre- and postnatal influences. Four children who had been exposed to several harmful intrauterine factors showed general developmental retardation. All the other childrens demonstrated normal physical development including the group who had shown signs of prolonged intrauterine malnutrition.


[Results of a follow up study of small for date babies. II. Mental development (author's transl)]. The second part of the follow-up investigation of 74 small for date babies presents the results of neurological investigation and psychological testing. A correlation was found between the period of the intrauterine noxa and the results. A third of the children in group I (where the intrauterine influences were more severe and more prolonged) had an IQ below average. Minor cerebral damage, poor school performance and mental disturbance were significantly more common than in group II. The EEG-investigation did not contribute additional information. In both groups social factors had an important influence.


[Staining of glial fibers (author's transl)]. A new modification of the Holzer-Kanzler method is recommended. For the staining a 0.1% alcoholic crystal violet solution is used, and the second mordanting is performed with 5% potassium odide.