A symptomatic discriminant to identify recurrent ulcer in patients with dysperpsia after gastric surgery. A questionnaire has been completed by 99 patients referred for investigation of symptoms after gastric operations. The replies were analysed in an attempt to distinguish patients with a recurrent peptic ulcer from those with no recurrent ulcer. All cases were investigated by barium meal, endoscopy, and oral cholecystography. All recurrent ulcers were confirmed by reoperation and patients with gastric carcinoma, gallstones, or symptomatic hiatus hernia were excluded. The study was retrospective in 40 patients in whom the diagnosis was already confirmed when the questionnaire was analysed and prospective in 59 in whom the diagnosis was originally unknown. The replies were analysed with (a) a small computer using Bayes' theorem, (b) weighted tables, and (c) a discriminant analysis. The computer prediction of the prospective data was 85% accurate. The results of simpler methods were almost as good as the computer prediction, and questions related only to the severity of pain and vomiting accurately distinguished recurrent ulcer from other causes of dyspepsia in 81% of patients.


Prognostic significance of inappropriate production of pregnancy proteins by breast cancers. 50 cases of cancer of the breast (diagnosed between 1962 and 1966) were studied retrospectively. An enzyme-bridge immunoperoxidase technique was used to demonstrate that so-called pregnancy-specific proteins were detectable in the cytoplasm of the tumour cells. Of the proteins studied, pregnancy-specific beta1-glycoprotein was present in 76% of cases, placental lactogen in 82%, and chorionic gonadotrophin in 60%. Those women with cancers negative for pregnancy-specific beta1-glycoprotein and placental lactogen had significantly longer survival-time compared with those whose cancers stained for these proteins. Pregnancy-specific beta1-glycoprotein appears to be the best indicator of prognosis. A prospective study is needed to determine whether those patients requiring adjuvant chemotherapy after mastectomy can be identified by staining tumour tissue for pregnancy-specific beta1-glycoprotein by the enzyme-bridge technique.


Cervical-mucus and basal body-temperature method of regulating births. Field trial. A field trial of combined use of the basal body-temperature and the secretion of cervical mucus as a means of regulating births is reported. 84 women followed the method through 1195 cycles between October 1, 1973 and May 31, 1976. There were 22 unplanned pregnancies.


A double-blind trial of ethamsylate in the treatment of primary and intrauterine-device menorrhagia. 22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device (I.U.C.D.) were studied in a double blind trial with crossover of ethamsylate and placebo. Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods, during which patients received ethamsylate ("Dicynene") treatment during two menstrual cycles and placebo during two cycles. During ethamsylate treatment the mean menstrual blood-loss was reduced by 50% in patients with primary menorrhagia and by 19% in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia. Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment. Reported side-effects, which were not serious, were equally common during ethamsylate and placebo treatment.


Sudden death caused by interaction between a macroglobulin and a divalent drug. Intravenous injection of the divalent X-ray contrast medium ioglycamic acid ("Biligram") induced intravascular precipitation and sudden death of a patient owing to reaction with his monoclonal macroglobulin. Mice reacted similarly in passive transfer experiments. The corresponding monovalent compound, acetrizoic acid, was also bound to the IgM but did not induce precipitation and had no apparent ill-effects on mice in passive transfer experiments.


Serum-prolactin in long-lasting lactation amenorrhoea. Basal serum-prolactin concentrations were high until 15 months post partum in nursing mothers in Central Africa (Lwiro). They were significantly lower in menstruating than in amenorrhoeic nursing mothers. These results support the hypothesis that prolactin is involved in the long-lasting amenorrhoea which occurs in regions where breast-feeding is prolonged for up to 2 years after delivery.


Small-cell carcinoma of the lung: attempt to remedy causes of past therapeutic failure. A regimen of intensive, cyclic chemotherapy (cyclophosphamide, vincristine, doxorubicin administered concurrently with radiotherapy of bulk disease plus prophylactic whole-brain irradiation has been investigated for small-cell carcinoma of the lung. Treatment was completed in 12 weeks, after which patients were observed without maintenance therapy. Complete clinical remissions were noted in twenty of twenty-one patients with unresectable tumours, 10 of whom had distant extrathoracic spread upon admission. Survival has been prolonged and nine of the eleven patients with regional disease (mediastinal adenopathy with or without pleural effusion and/or supraclavicular nodes) have remained clinically disease-free for 6-14 months (median 10) and have resumed normal activities.


"Self": standard of comparison for immunological recognition of foreignness. It is suggested that the markers of biological individuality--i.e. the HLA antigens--may serve as the standard profiles against which foreignness is directly compared.


Patients' awareness and desire for information about diagnosed but undisclosed malignant disease. 74 hospital patients with diagnosed but undisclosed malignancy were interviewed and observed to ascertain their awareness of their condition and desire for information about it. While 88% either knew or suspected that they had a malignant tumour at admission to the ward, the great majority of them had no wish to augment that knowledge. The fact that their diagnosis or prognosis was not revealed to them allowed many patients to maintain the hope either that they might not have cancer or that the outlook might be favourable.


Codeine intoxication in childhood.

Codeine intoxication in childhood. Clinical reports on 430 children with acute codeine intoxication are evaluated. Of 234 children who had taken more than 5 mg/kg body-weight, 8 had respiratroy arrest necessitating intubation and artificial ventilation; 2 of them died. In all other cases the intoxication produced one or more of the following symptoms: somnolence, ataxia, miosis, vomiting, rash, swelling, and itching of the skin, but no life-threatening side-effects. Close supervision of respiration is the main principle of management when more than 2 mg codeine/kg body-weight has been taken. Gastric voiding may be useful if done soon after ingestion. Charcoal and purgatives should be given in all cases.


[Modification of the Romeis method for cartilage staining]. When staining of the cartilage by the method of Romeis one can increase of the electivity using more acidic staining solution for a shorter period. For fixation instead of solution of ammoniummolibdate, solution of phosphotungstic acid is recommended.


[Basic proteins in the granules of mast cells. Demonstration of masked proteins, acidophilic staining of the granules]. Basic proteins of the granules of mast cells in nativ, formalin-, alcohol- and aceton fixed preparations without any preliminary treatment, when stained with acidic dye at the pH 9 cytochemically seem to be masked. After various preliminary treatment (treatment with acid, with cetylpiridinumchlorid, CPC) mast-cell granula stained with acidic-dye at pH 9 appear intensively acidophile. This phenomenon can be explained by the presence of basic proteins in the mast cell granula. Preliminary treatment with CPC inhibits acid radicals of the heparin. This may lead to the disintegration of the linkage between proteins of the heparin, thus amino-group of the basic proteins become reactivated and can be identified by acidic dyes. It can not be excluded as well, that CPC linked to the heparin with free positive radicals reveals acidic-dye-binding capacity. In cases of preliminary treatment with various acids this mechanism does not seem possible to lay on the base of changing of the dye binding capacity.


[Chlorinated hydrocarbons in the daily diet]. The gas chromatographic analysis of the daily diets (without beverages) of men consuming at maximum 4000 kcal per day, in spring, summer and autumn 1971, revealed always residues of chlorinated hydrocarbons. With an average food amount of 1635 g per day, each subject (having an average body weight of 65 kg) ingested 105 mug of DDT, 20 mug of DDE, 20 mug of DDD, and 149 mug of total DDT and 10 mug of lindane, respectively. The contamination was inferior to the ADI values recommended by the WHO/FAO. From winter 1971 to autumn 1972, the authors also analysed the daily diets (including beverages) of 1-3-year-old children (having an average body weight of 12 kg) in a week-nursery. The average food amount of 1230 g per day contained 42 mug of DDT, 12 mug of DDE, 8 mug of DDD, and 64 mug of total DDT and 7 mug of lindane, respectively. From these values a total DDT intake of 5.3 mug/kg of body weight was calculated which exceeds the ADI value for adults. The claim for a zero tolerance for victuals and ready-to-use baby foods is corroborated. Consequently the complete replacement of DDT by other insecticides is a measure which is imperative not only from the viewpoint of prophylaxis but also from that of health policy.


[Effects of DDT and lindane on thyroid function in the rat]. Using the previously described test method, the authors studied with the aid of iodine-131 labelled NaI the effects of daily doses of 30 and 75 mg DDT/kg of body weight, and of 12 and 36 mg of lindane/kg of body weight on the iodine and hormone metabolism in the rat. With DDT, the authors observed a marked increase of the thyroid mass and of the thyroid tri-iodothyronine and thyroxin levels and a simultaneous decrease of the thyroid iodine level. The values for serum iodine and protein-bound iodine were reduced. Serum thyroxin was slightly increased. Serum tri-iodothyronine was markedly increased, which was also true of the iodine fractions in the liver. Lindane was considerably less effective. Only the decrease of thyroid tri-iodothyronine and the simultaneous increase of thyroid thyroxin were striking. In the serum, both hormones remained unchanged. The values for the urine fractions of both the active principles were indicative of a hypofunction. The causes of the changes observed were discussed with regard to the findings of other authors. The present results permit the conclusion that the effects of the pesticides tested are obviously complex by nature.


125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection. 1. On unilateral injection of sublethal doses of 125I-botulinum A neurotoxin (BTA) into one gastrocnemius muscle of the cat we found after 48 h: a) A disto-proximal gradient of radioactivity (RA) had developed in the sciatic nerve of the injected side. b) The ventral roots of the spinal cord half segments supplying the injected muscle showed a higher RA than the ventral roots of the contralateral control side. c) The spinal cord half segments innervating the injected muscle had a RA much higher than the corresponding segments of the contralateral side. However, a small rise of RA was also observed in the contralateral half segments. 2. In histoautoradiographs of the (ligatured) ventral roots the RA was strictly confined to the intraaxonal space of a few nerve fibres. 3. On injection of equal doses of 125I-BTA into either gastrocnemius muscle we found after 38 h: a) Direct stimulation of only one of the injected muscle caused the RA to reach a higher level in the spinal cord half segments ipsilateral to the stimulated muscle than in the spinal cord half segments of the non-stimulated side. b) Unilateral stimulation of one gastrocnemius nerve under the influence of gallamine or unilateral antidromic stimulation of the dorsal roots L7, S1 failed to cause a difference in RA between stimulated and non-stimulated side.


Immunochemical and enzymatic studies on the soluble antigens of normal human kidney. The antigenic composition of the soluble extract from normal human kidney was determined with the combined techniques of immunological absorption, immuno-diffusion and immunoelectrophoresis. The kidney extract contained at least eleven non-serum, tissue antigens; some of them were found in the extracts of other organs, but three were kidney-specific. None of the soluble tissue antigens from human kidney was characterized as a lipoprotein; however, three of them stained with the reagent for glycoproteins. Esterase activities were also demonstrated in four non-serum, renal antigens, one of which was present only in the kidney extract and absent in the other organs extracts.


Evaluation of percutaneous kidney biopsy in advanced renal failure. As more information is gained on the long-term survival in chronic dialysis and transplant patients, it is unacceptable to be satisfied with a clinical impression of the etiology of the end stage renal failure in each case. It becomes important to know the histological diagnosis in patients who present with terminal renal failure. In the past there was little to offer such individuals in terms of therapeutics, and their prognosis was uniformly poor. Thus, biopsy for other than academic reasons was difficult to justify. This is no longer true and presented here is a series of 28 such patients in whom percutaneous renal biopsy was performed. The complications and diagnostic yield are reported. It is further demonstrated that the added knowledge of histological diagnosis can be of benefit to the individual patient.


[Recent advances and prospects in periodic hemodialytic treatment for patients with uremia]. Following a brief outline of the history of haemodialytic technique, the most relevant recent progress is illustrated. Advances include the success of the internal artero-venous fistula for access to the vessels, of "less than" single "greater than" haemodialytic units, of three-times-a-week dialysis, and the creation of new disposable dialyzers of high efficiency and low priming volume. Some of the problems posed by the patient in periodic haemodialysis are then examined (the problem involved in the risk of hepatitis, that of persistent severe anemia even after haemodialysis has been begun and that of osteopathy) and the most suitable measures for preventing or limiting these situations are presented. Finally, survival indices of patients undergoing periodic haemodialysis are examined and it is concluded that, although various clinical problems have as yet failed to find a complete solution, the patient under haemodialysis can enjoy a satisfactory state of rehabilitation to family and working life and survive even for more than ten years after the terminal phase of uraemia.


Serum protein fractions. Effects of oral contraceptives and pregnancy. As a part of a longitudinal study to determine the side effects of oral contraceptive drugs (OCs), protein electrophoresis studies were carried out on sera obtained from 4057 current users of OCs, 9774 nonusers, and 624 women in the first trimester of pregnancy. Albumin and gamma globulin levels were lower in OC users than in nonusers; alpha-1, alpha-2, and beta fractions were higher. A similar effect was observed during the first trimester of pregnancy. The changes were temporary and reverted to normal within 12 weeks of OC withdrawal. The dosage of the estrogenic component appeared to be directly related to the lower concentration of albumin in users. The mechanisms of these changes were not well identified but very likely represent a direct effect on the metabolism of proteins.


Sealing quality of polycarboxylate cements when compared to amalgam as retrofilling material. Four hundred roots were uniformly prepared for retrofilling. One hundred of these were retrofilled with amalgam and served as controls for the study. The polycarboxylate cements--Durelon, PCA, and Poly C--were each used as retro-filling material for 100 roots. After immersion in 2 per cent aqueous methylene blue for 7 days, the roots were sectioned in 1 to 2 mm. increments to determine the depth of dye penetration. The depth of dye penetration was used as a measure of their sealing effectiveness. The groups were compared statistically by means of a t test. All cements were significantly different from amalgam. All cements performed inferiorly to amalgam, an already accepted retrofilling material.


[Localization of HBsAg, immunoglobulins, fibrin and C3 in the liver by direct immunoflourescence]. Liver biopsies of sixty patients with different forms of hepatitis and ten control subjects without hepatic disorders were examined by means of direct immunofluorescent methods for the HBsAg, immunoglobulins, fibrin and C3. The presence of fluorescent particles of HBsAg in the cytoplasm of hepatocytes were correlated with the presence of HBsAg in the serum. The fluorescence did not seem specific of histological stage of hepatitis. Immunoglobulins and fibrin were often demonstrated in hepatic sinusoids, especially in chronic aggressive hepatitis. In contrast, C3 is rarely observed.


Uptake of the mosquito larvicide Temefos by the salt marsh snail, New Jersey--1973-1974. Uptake of the mosquito larvicide temefos (Abate) by the salt march snail (Melampus bidentatus Say) in New Jersey was measured by gas-chromatographic analysis. Measurable quantities of temefos were found in the snails within 1 day after the first treatment with a 2% granular formulation but 3 weeks elapsed before uptake occurred following treatment with a temefos emulsion. Residues in the snails exposed to the granular formulation were generally more than 10 times higher than those in snails exposed to the emulsion although application rates of the granular formulation were only about three times higher than those of the emulsion. Residues in snails exposed to the emulsion fell below detectable levels less than 3 weeks after cessation of treatments although measurable amounts were found in snails exposed to the granular formulation for more than 5 weeks after the last treatment. The persistence of temefos in M. bidentatus suggests the potential for its movement through food webs exposed to the granular formulation.


Appraising current therapy for breast cancer. 2. Irradiation. The best combination of methods for managing primary breast cancer may not yet be known. Radiation therapy has been proved effective in decreasing the incidence of local and regional recurrence following mastectomy. Thus, until a superior regimen is established, I recommend local and regional irradiation for patients at high risk for recurrence. Local irradiation is also an effective means of achieving palliation of symptoms associated with metastatic disease.


Purification of canine plasma renin by affinity chromatography. An affinity column for the purfication of canine plasma renin was prepared using goat anti-renin (dog kidney) gammaG gloublins. The antiserum was prepared against a purified kidney renin preparation. The anti-renin globulins were coupled to cyanogen bromide activated Sepharose. Using the anti-renin globulin-coupled Sepharose as an immuno-adsorbant, a method was devised allowing purification of plasma renin to a 1,000-fold purity.


Synthesis of extensive, possibly complete, DNA copies of poliovirus RNA in high yields and at high specific activities. The synthesis of large, possibly complete, complementary DNA (cDNA) copies of poliovirus RNA by avian myeloblastosis virus DNA polymerase is described. The cDNA consists of two size classes, the larger of which is approximately 7500 nucleotides. In the presence of excess deoxynucleoside triphosphates, ribonucleoside triphosphates, or sodium pyrophosphate, only the larger material is obtained. Yields of the large cDNA are 50-75% of the input RNA.


Characterization of the collagen synthesized by endothelial cells in culture. [14C]Proline and [14C]lysine were incorporated into collagen by cultures of endothelial cells derived from calf aortae. The isomer 3-hydroxy[14C]proline accounted for 10% of the total hydroxy[14C]proline in the collagen isolated from the medium. Approximately 81% of the hydroxy[14C]lysine isolated from the medium was glycosylated, and 91% of the glycosylated hydroxy[14C]lysine was in the form of the disaccharide glucosylgalactose. Gel filtration chromatography or acrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that the initially synthesized peptide chain of [14C]collagen had a molecular weight of about 135,000; after pepsin digestion this was converted to 115,000. The ratio of hydroxy[14C]proline to total [14C]proline x 100 in the pesin-resistant fraction was 59. When examined by immunofluorescence microscopy, the endothelial cultures stained positively with antiserum to (Type IV) collagen from basement membrane of bovine anterior lens capsule. The data indicate that cultured endothelial cells derived from calf aortae synthesize collagen that resembles that of basement membrane collagen.


Simian virus to (SV40) tumor-specific proteins in nucleus and plasma membrane of HeLa cells infected by adenovirus 2-SV40 hybrid virus Ad2+ND2. HeLa cells infected with the nondefective adenovirus 2-SV40 hybrid virus (Ad2+ND2) have previously been shown to synthesize two SV40-specific proteins with molecular weights of 56,000 (56 K protein) and 42,000 (42 K protein). The present study demonstrates that these proteins are immunoprecipitable with serum from hamsters bearing SV40 tumors. By peptide analysis, it is shown that the 56 K and 42 K proteins share common amino acid sequences. Both proteins are metabolically stable in nuclei and plasma membranes but unstable in the cytoplasm, as shown by pulse-chase experiments and cell fractionation studies.


[Experimental allergic encephalomyelitis as a model for the study of therapeutic concepts for encephalomyelitis disseminata]. The induction of immunological tolerance with, and for, the caused organotypical antigen is a conception for a specific therapy for neuroimmunological diseases with at least a partial autoallergic pathogenesis. Appropriate to a set step-by-step programme for the development of antigen-specific therapy preventive tolerance experiments were carried out at the model of experimental allergic encephalomyelitis (EAEM) with allogenic myelin basic protein (BP) prepared from rabbits. The result is: 100 ug BP given intravenously simultaneously with 100 ug BP in incomplete Freud's adjuvant given intracutanously twice a week and 40 mg Cyclophosphamid given daily during the minor clinical incidence rate and no signs of EAEM pathomorphologically. A longlasting tolerance for the BP could be obtained as a test proved after 100 days. Hints are given for further potential therapeutic treatments, such as the use of antigen bound chemically to the immunosuppressive drug or the use of chemically modified BP for the induction of a specific tolerance.


Euflavine: effect on brain heavy metal content and staining pattern, and on shuttle box behavior in goldfish. Goldfish were exposed to euflavine in doses of 7-100 mg/l for 1h-14 days. The treatment resulted in a reduced stainability of the brain with the Timm histochemical procedure for "heavy metals". In contrast, analysis by flameless atomic absorption spectrophotometry showed no significant changes in the concentrations of zinc and of copper after euflavine treatment. In the shuttle box a significant increase in general activity was found. These results, compared to earlier work with other chelating agents, indicate that such drugs do not have a uniform effect on behavior, and that they do not cause a true depletion of heavy metals in the brain.


Experimental studies on drug sensitization. II. Production of antiacetylsalicylyl antibodies and their detection by passive hemagglutination. Antiacetylsalicylyl antibodies were produced in rabbits and guinea-pigs by innoculation of acetylsalicylic acid incorporated in Freund adjuvant. These antibodies were readily detected by a passive hemagglutination test using rabbit erythrocytes incubated with acetylsalicylic acid at alkaline pH. Acetylsalicylyl conjugates with human gammaglobulin, bovine gammaglobulin and rabbit gammaglobulin were also prepared by incubating the proteins with acetylsalicylic acid at alkaline pH. In parallel experiments, salicylic acid did not induce formation of specific antibodies capable of reacting with acetylsalicylic or salicylic acid-treated erythrocytes.


Radiotherapy of metastases of mammary carcinoma. Radiotherapy is a very successful way of treating localized metastatic or recurrent breast cancer. The success of treatment depends largely on the site of the metastasis and the dose applied. It is not a substitute for systemic treatment, but superior in the treatment of localized disease.


[Studies on human alpha-2 macroglobulin structure and its complexes with proteases, using polyacrylamide gel electrophoresis]. Pure alpha2M is prepared with fresh plasma as starting material, to prevent the interaction of alpha2M from proteolytic enzymes of plasma such as thrombin, plasmin and kallikrein. During the purification steps, polybrene and aprotin are used as inhibitors and plasminogen is absorbed onto bentonite. When alpha 2M is submitted to polyacrylamide gel electrophoresis (PAA) containing 0.1% SDS, a complete dissociation in two half-molecules of MW 380,000 occurs. When alpha2M is incubated in 1% SDS and 1% beta-mercaptoethanol as reducing agent, only one component of MW 190,000 is observed in PAA-SDS. This experiments show that the alpha2M molecule consist of two symetric halves of same MW (380,000) linked by non covalent bonds. Each two-half-molecules is made of two polypeptides chains MW 190,000 linked by disulfide bonds. Thus alpha2M molecule contains four polypeptides chains having a same MW. The same techniques were applied to the study of alaph2M proteinases complexes. Three different proteinases (plasmin, trypsin and papain) were used in these experiments. Trypsin and papain are commercialy available. Plasminogen was obtained by affinity chromatography and activated into plasmin by insoluble streptokinase fixed on PAB cellulose.


Complex nature of the production of 'effector' cells and their interaction with target cells in the M-antigen system of the mouse. The capacity of lymphocytes from mouse strain CBA to generate 'effector' cells against the H-2-compatible, M-antigen-incompatible strain C3H and their interaction with such target cells were investigated. It was observed that CBA lymphocytes injected in, and 5 days later obtained from, the spleens of irradiated C3H X CBA hybrids ('educated cells') could strongly inhibit the growth of C3H X CBA bone marrow cells but were almost nonresponsive to C3H X C57BI bone marrow targets (H-2-incompatible). CBA lymphocytes educated in irradiated C3H X C57BI hosts displayed reactivity against C3H X C57BI and CBA X C57BL but not against C3H X CBA bone marrow target cells. Additional tests indicated that the M antigen determined by C3H is expressed to approximately the same extent on C3H X CBA and C3H X C75BL cells and that the M antigen on C3H does not cross-react immunologically with antigens on C57BL cells. Moreover, it was observed that CBA X C57BI lymphocytes were triggered to cell proliferation by C3H antigens but were unable or had a highly reduced capacity to develop 'effector' cells in response to this antigenic stimulus. These results indicate that generation of 'effector' cells and their interaction with target cells are very complex processes.


IgA in secondary anti-hapten responses in vitro. Production of IgA anti-hapten antibodies in vitro was studied in suspension and fragment cultures of spleens from mice immunized with NIP-CG (4-hydroxy-5-iodo-3-nitrophenylacetyl coupled to chicken globulin) a few weeks earlier. IgA anti-hapten production tended to be of much shorter duration than IgG anti-hapten production. IgA produced in fragment cultures had sedimentation coefficients of 9S, 11S, and 13S. 9S IgA anti-hapten was more prominent later during the in vitro response than earlier. In suspension cultures IgM anti-hapten production preceded IgA and IgG anti-hapten production. Very little IgM anti-hapten was seen in fragment cultures, although the responses on a cell-to-cell basis tended to be much higher in fragment than in suspension cultures.


Impact of Ig-anti-Ig column fractionation on T-lymphocyte functions. C57Bl/6 anti-Pe15-immune spleen cells were fractionated on immunoglobulin (Ig)-anti-Ig antibody columns in medium containing EDTA or in EDTA-free medium. The antigen-specific cytotoxic potential of immune cells in vitro was only slightly enriched after passage through the columns in the absence of EDTA, whereas immune cells passed through the columns in the presence of EDTA displayed a cytotoxic potential enriched about three times compared with unfractionated cells; this is similar to the enrichment in theta-positive cells. The lack of increase of the cytotoxic potential of immune cells after passage through the columns in the absence of EDTA was shown to be due to the adsorption of subpopulations of cytotoxic T lymphocytes. These cytotoxic cells could be eluted with EDTA-containing medium, and the findings suggest that their adsorption may be mediated via the interaction between cell-bound Fc receptors and the column antigen-antibody complexes.


Surface markers on human B and T lymphocytes. VIII. Association between complement and Epstein-Barr virus receptors on human lymphoid cells. An association has been found between the Epstein-Barr virus (EBV) and complement (C3d) receptors on human lymphoid cells. The evidence was four-fold: there was a correlation between the expression of these two receptors; inhibition experiments showed that the binding sites probably are close to each other in the cell membrane, although not identical; EBV and complement receptors have been found to co-cap in either order; and lymphoid cell lines lacking complement receptors could not be superinfected with EBV.


A method for determining plasma proteins in inflammatory exudate absorbed by Sephadex. Dry cross-linked dextran (Sephadex pharmaceutical grade, Debrisan) was applied to weeping sores. After some exudate had been absorbed the gels were removed. The amount of exudate was determined by isotope dilution techniques. The accuracy of the method was tested by determination of plasma proteins in samples of diluted serum containing known concentrations of some plasma proteins. The method seems suitable for determining various high and low molecular weight constituents of exudates.


Detrusor hyperreflexia. A survey on its etiology and treatment. Detrusor hyperreflexia (DH) is a frequently occurring condition. The symptomatology is characterized by frequency, urgency and urge incontinence. DH is defined as involuntary, uninhibited detrusor contractions. The physiology and pathophysiology of the micturition reflex is reviewed. The balance between cerebral stimulation and supraspinal inhibition is discussed. DH is caused by disturbances in this balance. Whereas increased afferent impulses to the central nervous system due to local disorders in bladder and/or urethra may produce DH, a neurological disorder affecting the inhibitory nervous pathways from cortical and subcortical centres always result in uninhibited detrusor contractions. DH was found in 25% of 2000 patients. In the majority of the patients the DH was caused by a neurological disorder. The incidence of DH in patients with enuresis, gynecological patients with urinary incontinence and/or genital prolapse and patients with benign prostatic hyperplasia (BPH) is reported. In 62% of the patients with BPH the DH was eliminated after adequate surgical treatment of the infravesical obstruction. By contrast, DH in women with genital prolapse and/or incontinence persisted despite operative treatment. In a retrospective investigation of 152 patients with DH, the cause of the DH was unknown in 32 patients (21%). A clinical neurological examination revealed no evidence of neurological disease in 45% of the 22 patients examined. Voiding symptoms were the only complaint in these patients as well as in 30-40% of the patients in the other groups mentioned. This calls for improved investigatory methods in the evaluation of the balance between stimulation and inhibition of the micturition reflex. The presence of uninhibited detrusor contractions in apparently healthy patients should indicate a neurological examination since DH may be the first sign of a neurological disorder. The micturition reflex is conducted through long, uninterrupted neurons with a marked central integration. Therefore cystometry may be used as a supplement to the clinical neurological examination in the early diagnosis of pyramidal or extrapyramidal central nervous system disorders.


Long-term shunt palliation for Fallot's tetralogy. One hundred and sixty-two systemic-pulmonary shunts of various types were performed in 136 patients with Fallot's tetralogy. There were 72 Blalock-Taussig shunts, 31 Potts and 24 of Waterston shunts. Furthermore, systemic-pulmonary anastomoses with interposed grafts were made in 34 cases. The patients were followed up for 1 to 23 years, average 12 1/2 years. The total mortality varied from 25% in the Waterston group to 42% in the Potts group. The immediate palliative effect of the shunt operation in the surviving patients seemed to be independent of the type of shunt used. At follow-up, 9 of 69 patients originally operated upon with a Blalock-Taussig shunt were alive with their original shunt, while the corresponding figure in the Potts group was 12 of 30. More than 20 years after palliation, one of 15 patients were alive with an original Blalock-Taussig shunt and 9 of 22 with a Potts anastomosis. Surgical problems in construction of the shunts and the long-term results are briefly discussed.


Biochemical evidences for ribonucleic acid viral-like characteristics in malignant diseases of gastrointestinal tract and lung in humans. It has been demonstrated that malignant diseases of the gastrointestinal tract and lung in humans possess three characteristics invariably found in ribonucleic acid tumor viruses: the presence of a ribonucleic acid directed deoxyribonucleic acid polymerase, reverse transcriptase; a high molecular weight ribonucleic acid with a sedimentation coefficient of 70 Svedberg units, and particulate elements with densities of 1.16 to 1.18 grams per milliliter sucrose gradient. Twelve of 17 carcinomas of the colon, three of five carcinomas of the stomach, all three carcinomas of the rectum and seven of ten carcinomas of the lung displayed detectable evidence of these viral-like entities. None of the corresponding normal tissues had positive reactions.


A rapid method for preparing tissue culture clones for light and electron microscopy. Fixation and epoxy-embedment of tissue culture clones in situ were carried out in Falcon tissue culture plates. The clone of cells, retained at one end of the casting, was stained with azure II-methylene blue and then studied with the oil immersion objective. The dimensions of the epoxy casting were ideal for mouting as a block in conventional ultramicrotone chucks. The use of one epoxy casting permits a single preparation of tissue culture clones for direct light microscopic observations and subsequently for ultramicrotomy.


Comparative in vitro studies of a number of anti-mastitis antibiotics. In vitro activities of penicillin, ampicillin, dihydrostreptomycin, nafcillin, cloxacillin and commercially available combinations of these antibiotics against a variety of Gram-positive mastitis-causing micro-organisms were examined. As a rule, penicillin proved to be more active against penicillin-sensitive strains of micro-organisms than ampicillin and nafcillin and far more so than cloxacillin. In combination with di-hydrostreptomycin, which in itself showed hardly any activiy, the activity of penicillin against streptococci was enhanced considerably. This confirms the synergistic effect of this combination. No clear synergism was noted in the activity against staphylococci. Against strains which were less sensitive to penicillin, there was not much difference in activity between penicillin, ampicillin, nafcillin and cloxacillin. Nafcillin was found to be much more active against streptococci than cloxacillin. The anti-staphylococcal activities of these two antibiotics however were identical. The activity of the combination of penicillin, dihydrostreptomycin and nafcillin against most micro-organisms was mainly due to the penicillin in the combination. Against Streptococcus agalactiae and the most penicillin-resistant staphylococci, nafcillin contributed clearly to the activity. The activity of the combination ampicillin + cloxacillin against Streptococcus agalactiae was mainly based on the activity of the ampicillin in the combination. Against penicillin-resistant staphylococci, the activity of the combination was mainly due to the activity of cloxacillin. Against the other micro-organisms, both compounds contributed to the activity of the combination.


Lymphocyte stimulation by soluble subcellular fractions. Nuclear material can produce inhibition or stimulation of healty leucocytes under different experimental conditions, Reactivity could not be produced in cultures using intact nuclei and allogeneic lymphocytes. The effect of nuclear and cytoplasm fractions was compared with that of whole cells on intact healthy lymphocytes. The HLA activity in the individual fractions was assessed. Stimulation was produced by certain nuclear and cytoplasmic fractions and these were closely related to the peaks of HLA activity. The response to these fractions showed less activity than that achieved in conventional one way MLC tests.


Typing for HLA-D determinants. comparison of typing results using homozygous stimulating cells and primed cultures. Typing for HLA-D determinants, using primed lymphocyte typing (PLT), has been compared to the results obtained using conventional homozygous stimulating cell primary MLC tests. The HLA-Dwl, -Dw2 and -Dw3 specificities were studied. Preliminary results indicate that these two methods essentially type for the HLA-D determinants and that reproducible results can be obtained employing the PLT technique after 24 hours of incubation in the secondary cultures.


HLA antigens and acquired valvular heart disease. The frequency of HLA antigens was determined in 133 patients with acquired valvular heart disease and compared with the frequency of HLA antigens in 1,000 normal individuals by the relative incidence ratio method of Woolf (1955). No significant increases were observed. However, when the patients were divided into those with no rheumatic history and those who have had rheumatic fever or chorea, a significant increase in AW 30/31 and A29 was observed in the group with no rheumatic history.


Histocompatibility (HLA) antigens and diabetic microangiopathy. To gain further insight into the genetic determinants of diabetic small vessel disease, we studied 22 HLA antigens in 110 juvenile-onset, insulin-dependent diabetics with terminal glomerulosclerosis and retinopathy, who were being prepared for kidney transplant. HLA antigens were comtemporarily determined in non-diabetic kidney transplant recipients and healthy controls. The frequency of antigens A1 and B8 were significantly higher in diabetics than in controls (P less than .02 and .011), but the frequency of BW15 was normal. The data are compatible with the concept that juvenile diabetes with microangiopathy is one of the HLA-B8 associated disorders.


HLA antigen (A & B loci) frequency in Addisonian pernicious anaemia. Sixty-six patients with Addisonian pernicious anaemia have been HLA typed and compared with 86 controls of the same ethnic group. No deviation in antigen frequency was found to be specific for the disease group as a whole. The most significant deviation found was an increased frequency of HLA-B8 in those patients with coincident thyroid autoantibodies. Pernicious anaemia seems to be the exception to the demonstrated association between HLA-B8 and the organ specific autoimmune diseases studied up to the present time.


The use of methyl green-pyronin staining after glutaraldehyde fixation and paraffin or araldite embedding. Methyl green-pyronin staining has been used for localization of RNA and DNA in chick and mouse embryonic tissues and in insect larval salivary glands. Glutaraldehyde or tricholoracetic acid-lanthanum acetate (TCA-LA) was used as fixative and paraffin wax or Araldite was used as embedding medium. For good results the following are specially desirable: fixation with 2.5% glutaraldehyde, dehydration in alcohols for short time, and the use of fresh staining solutions. After TCA-LA fixation the final results are much less specific. The digestion with RNAse appears essential for the detection of RNA because pyronin does not seem to be entirely specific to RNA. The results show that glutaraldehyde a common fixative for electron microscopic work, is particularly suitable fixative for light microscopic cytochemical investigations if followed by methyl green-pyronin staining; furthermore, methyl green-pyronin staining after glutaraldehyde fixation can be carried out on Araldite sections.


The specificity of antisera raised by oestradiol-17beta-3-hemisuccinyl-bovine serum albumin. The preparation of pure oestradiol-17beta-3-hemisuccinyl-bovine serum albumin conjugate is described. Contrary to previous findings this antigen raised reasonably specific antisera in rabbits which possessed a cross reaction of only 2.0% with oestrone, and 0.8% with oestriol. The production of this specific antisera is considered to be due to the high purity of the antigen. The role of the C-3 phenolic hemisuccinyl linkage of the antigen in raising this specific antisera is discussed.


B-cell antibodies, Ia-like determinants, and their relation to MLC determinants in man. The HLA supergene is located in the 6th chromosome. Its position to the centromere and the position of a number of polymorphic isoenzymes has been elucidated. The HLA supergene codes not only for determinants present on all nucleated cells, but also for determinants present on B cells and absent from T cells and platelets. These determinants can be recognized by serology, and evidence is presented that some of them are coded for by a hither to unrecognized locus Ag, which is very closely linked to the MLC determinants of the D locus can be recognized with the help of the MLC test using unprimed cells, homozygous for the MLC determinants, so-called typing cells primed against one MLC determinant in the PLT test. So far, 8 MLC determinants have been recognized. Significant disease-association studies in different racial groups appear to be especially informative. They already indicate that the association found so far must rest on different mechanisms. Whether some of them could be caused by partial deficiency for one or more of the complement factors remains to be proven.


Ia antigens: isolation, chemical modification and structural characterization. The results described above, with respect to the similarity of basic structural features of Ia and H-2 antigens (see Table V), led to the evolutionary concept presented in Figure 10 according to which these antigens are the products of tandem-duplicated genes. The evolution of MHC-gene products is reflected by the basic structure of these molecules. This structure is compatible with basic repetitive units of molecular weight 12,000 as suggested by the selective cleavage of the intact protein by, for example, papain.


Allograft immunity to histocompatibility and organ-specific antigens. An experimental model has been developed in the dog in which a renal allograft was placed in the neck, leaving one of the dog's own kidney in situ. Five nonimmunosuppressed pairs of dogs have been studied by using the leucocyte migration test (LMT) as an in vitro measure of cell-mediated immunity. Antigen preparations from leucocytes, kidney, liver, and skeletal muscle from both the kidney donor and the recipient were used in the LMT in order to study responses against transplantation and organ-specific antigens. Inhibition of migration with donor-specific leucocyte and kidney antigens was detectable prior to clinical evidence of rejection, which was confirmed histologically. Concurrently, inhibition was also observed with autologous kidney antigen and histological damage was noted in the recipient's own nontransplanted kidney, accompanied by increasing proteinuria. Autologous serum withdrawn daily and added to the test culture medium abolished the inhibition of migration, thus suggesting the development of blocking factor.


Isolation and characterization of tumour-specific antigen from the serum of rats bearing transplanted aminoazo dye-induced hepatomas. Tumour-specific antigen has been purified from the serum of animals bearing large progressively growing transplants of an aminoazo dye-induced hepatoma (D23). Antigenic activity was detected by the capacity of serum fractions to neutralize reactivity of antibody in hepatoma immune serum for cell surface expressed antigen on viable hepatoma cells as assessed by using the indirect membrane immunofluorescence test. Serum from animals bearing large i.p. grafts of tumour was fractionated by gel filtration on Sephadex G-150 columns at pH 7.3 and pH 2.8 to yield a crude antigen fraction which was further purified by affinity chromatography by using syngeneic rat hepatoma D23 immune IgG insolubilized on Sepharose 4B. The purified antigen exhibited a pI of approximately 4.6 on analytical gel isoelectric focusing. Molecular weight determination on Sephadex G-200 at pH 7.3 in nondenaturing buffer indicated a primary molecular weight of 55,000 and a small amount of aggregated material (mol. wt. greater than 250,000).


Guinea pig histocompatibility antigens. I. Serological and genetic characterization of GPLA antigens. Lymphocytotoxic alloantisera were obtained by cross immunization among outbred guinea pigs from a closed colony. Groups of antisera recognizing the same specificities were established by panel analysis, cross immunization among appropriate phenotypes, and absorption studies. Three antigens designated B1, B2, and B3 (perviously B, C, and D) were detected in our outbred colony and also found to be present in a wide variety of guinea pig strains. These antigens were shown by population and breeding studies to be allelic gene products of a first guinea pig locus (GPLA) (designated locus B). Four new guinea pig families homozygous for their B locus antigens are now in the seventh generation of inbreeding.  NIH guinea pig strains 2 and 13, which share the B1 antigen, differ by a number of other antigens which have been designated I1, I2, I3 (previously A), and I4. These antigens differ from the B locus gene products in their molecular size and tissue distribution and it is, therefore, postulated that they represent an equivalent of the Ia antigens in mice (designated I region). Cross immunizations among inbred or outbred guinea pigs identical for currently known B locus and I region antigens yield further antisera, possibly recognizing additional Ia specificities and/or a second GPLA locus designated locus S. Whereas the conventional eosin lymphocytoxicity technique easily permits the detection of the widely distributed antigens (such as the B locus antigens), a more sensitive 51Cr release technique is required to demonstrate the "Ia equivalent" antigens of the guinea pig, possibly due to their restricted presence on the membrane of only some lymphoid cell populations.


[Cooperative sorbtion  of trypaflavin by glycerinized muscle fibers. I. Adsorption isotherm and changes in the fluorescence polarization of the sorbed dye]. The equilibrium binding of a fluorescent cationic dye Tripaflavine (TPF) by frog's glicerinated mucle fibres is described by a S-shaped isotherm: the Langmuir sorption at low dye concentrations in the medium (0.84-10-5--3.38-10-5 M) is followed by the cooperative binding with the increase of concentration (8.45-10-5--338.0-10-5 M). The appearance of new TPF binding centres, alteration in fluorescence anisotropy of sorbed dye as well as inactivation of myosine ATPase of model fibres at high concentrations indicate that the cooperative phase of sorption is characterized by changes in the structure of contractile proteins.


[Identification of several chromosome aberrations in man by the fluorescent method using quinacrine yprite]. The applications of the fluorescent staining of chromosomes with quinacrine mustard allowed to identify a dicentric Y-chromosome in two patients with defected external gynaetalies: a boy of 15 years old and a girl of 2 years old. Both the patients had mosaicism of sex chromosomes: 45, x/46, x dic (Y). The dicentric Y-chromosome, resembling chromosome, 16, had bright luminescence of the thelomeric regions characteristic of the normal Y-chromosome. Besides, a balanced autosomic translocation t (1, 14) (q 31, q 3) was found in the girl identified also with quinacrine mustard fluorescent staining.


[Proof of the formation of covalent bonds during staining of histologic preparations with procion dyes]. A method proving the formation of covalent bonds between a procion dye and histological slides is suggested based on the splitting of the covalent bound dye (I) into two parts, and on the synthesis of a new dye (II) on one of the parts of the dye (I) which was bound up with a covalent bond. If covalent bonds have not been formed while staining the slides a new dye (II) is not synthesized because two parts of the dye (I) have passed into solution.


Initial resistance of Mycobacterium tuberculosis in Northern Nigeria. Of 61 isolates of Mycobacterium tuberculosis form patients in northernn Nigeria denying any previous treatment for tuberculosis 7 (11.5 per cent) yielded resistant cultures. Four (6.6 per cent) were resistant to isoniazid, 2 (3.3 per cent) to PAS (1 also to thiacetazone), and 1 (1.6 per cent) to streptomycin. No mycobacteria other than M. tuberculosis were isolated from these patients. These results suggest that the level of initial drug resistance in northernn Nigeria may be lower than that found in other African countries.


Oncornavirus-like protein expression in human prostatic tissue. A sensitive competition radioimmunoassay using 125 I-labelled p 30 interspecies antigen, antiserum specific to the interspecies antigen of the feline leukaemia virus, and aqueous tissue extracts from prostate was used to examine benign hyperplastic prostates for the presence of protein components able to complete with the interspecies viral antigens. Six of 20 prostatic nodular hyperplastic tissues were competitive in radioimmunoassay with the 125 I-labelled viral antigen for binding sites on the antiviral antibodies. These findings suggest the presence of oncornavirus-like proteins in prostatic nodular hyperplasia. No correlation could be made between the presence of competing protein and histological features of acute or chronic prostatitis and squamous metaplasia.


The autonomic innervation of the human prostate. Histochemistry of acetylcholinesterase in the normal and pathologic states. The pattern of innervation of fibres containing AchE was examined by histochemical methods in fresh frozen sections of normal adult prostate, benign nodular hyperplasia, carcinoma of the prostate and the prepubertal prostate. Significant differences between the four groups investigated have been found.


Is nocturia of prostatism secondary to renal concentrating defect? An attempt was made to demonstrate a relationship between the nocturia of prostatism and decreased renal tubular concentrating capacity. Nos such relationship could be substantiated. In the absence of hydronephrosis, nocturia remains best attributed to detrusor instability and a decreased effective vesical capacity.


Conformation of adsorbed gamma-globulin and beta-lactoglobulin. Effect of surface concentration. The conformation of both adsorbed gamma-globulin and beta-lactoglobulin is dependent on surface concentration. Infrared bound fraction measurements show that the fraction of adsorbed carbonyl groups decreases as the amount adsorbed increases, while the ellipsometrically measured extension is higher for adsorption from higher concentration solutions. Similar studies with a cross-linked gamma-globulin preparation indicate that the native conformation in solution corresponds to an adsorbed conformation intermediate between those found at the extremes of high and low surface concentration.


Alternatives for plasma fractionation.

Alternatives for plasma fractionation. At the present time there is an enormously increasing demand for albumin. The most common procedure for the isolation of this plasma component is the cold ethanol technique developed by Cohn. Because this process necessarily isolates other blood components for which there is less demand in relation to albumin, albumin production is expensive. Therefore, we have developed a two-step fractionation for the isolation of albumin. It is basically a heat precipitation method with the albumin yield being about 90% of the original plasma albumin. In comparison to cold ethanol methods, it is considerably less expensive. Other blood components, e.g., clotting factors, immunoglobulins, may also be isolated. A nonmodified gamma-globulin for intravenous use is obtained by removing anti-complementary activity with hydroxyethyl starch. Additional fractionation steps are required to isolate these other components, but unlike in established methods, these are not necessary for the isolation of solely albumin.


[Protein-analytical studies on the serum and urine of patients with visceral lupus erythematosus]. Serum and urine of patients with ascertained lupus erythematodes visceralis were separated by means of the polyacrylamide gel pore gradient electrophoresis on the same experimental conditions. Deviations from the normal electropherogram were found in the serum within the gamma-globulins. For the demonstration of antinuclear factors the loose body test, the LE-cell test as well as the immunofluorescence test were carried out. In the uropherogram a highly molecular protein band could be proved which did not appear in the serum. In this fraction an immune complex which developed in the area of the kidney might be in question. It is referred to the possibility of the use of the PAA-polyacrylamide gel electrophoresis for the early recognition of renal changes.


[Blood group specific properties of leucocyte nuclei (author's transl)]. The absorbing and precipitating capacity of leucocyte nuclear suspensions derived from conserved blood of various blood groups was examined with anti-A-, anti-B-, anti-H, anti-M-, anti-N-, and anti-CDE-, and anti-D-sera as well as with anti-AHP- and Evonymus-extracts. Nuclei of blood group A absorbed anti-A, but not anti-B; nuclei of blood group B absorbed anti-B, but not anti-A. Nuclei of blood group 0 absorbed anti-H, but neither anti-A nor anti-B. Anti-M-, anti-N-, anti-CDE-, and anti-D-sera showed no absorption effect after incubation with leucocyte nuclei of corresponding blood groups. A nuclei were strongly precipitated by anti-AHP; B- and 0-nuclei were markedly precipitated by Evonymus-extract. B- and 0-nuclei showed only a weak precipitation with anti-AHP-extract; A-nuclei were only slightly precipitated by Evonymus-extract. Hence, leucocyte nuclei possess blood group specific properties, which, according to the present studies, are limited to certain blood group systems.


Collagen-induced acute synovitis in collagen-immunized rabbits. Thirty rabbits were investigated in 3 groups: a) one consisting of non-immunized animsls which were injected intraarticularly with human soluble collagen, human gammaglobulin or saline, b) the other consisting of human gammaglobulin-immunized animals which were injected with human soluble collagen and human gammaglobulin into the knee joints, and c) the third consisting of human collagen-immunized rabbits which were injected with human soluble collagen and human gammaglobulin into the knee joints. Eighteen hours after injection animals were sacrificed, joint fluid collected, cell number in fluid determined and synovial tissue prepared for histologic investigation. Distinct acute synovitis was observed in collagen injected knees of collagen immunized rabbits, as shown by distinctly increased cell number in fluids and histologic investigation. In comparison to collagen- or gammaglobulin injected knees of non-immunized animals, increase in cell number of collagen injected knees of collagen injected animals was statistically significant with P less than 0.005 respectively with P less than 0.01, and with P less than 0.025 in comparison to gammaglobulin injected contralateral knee. Distinct acute inflammation was observed morphologically in synovial tissue of collagen injected knees of collagen immunized animals only. Acute synovitis was also observed in positive controls, i.e. gammaglobulin injected knees of gammaglobulin immunized animals. These observations show, that appearance of collagen in molecular disposable form can induce acute inflammation of joints in state of collagen immunization.


[The concentration of antibodies to several exoenzymes of beta-hemolytic streptococci in commercial preparations of gamma globulin]. For the purpose of possible use of commercial preparations of homologous gamma-globulin in the outbreaks of streptococcus affections the authors studied the content of antibodies to some streptococcus antigens, namely to O-streptolysin, streptohyaluronidase and streptokinase. High antibody titres to streptokinase were observed in 62.7, to O-streptolysin--in 35.2 and to streptohyaluronidase--in 15.4% of the batches under study. The greatest amount of antibodies to all the antigens under study was revealed in gamma-globulin prepared from the blood sera collected during the automno-winter period of the year.


[The effect of D-penicillamine on experimental allergic arthritis in rabbits]. The effect of D-penicillamine on experimental allergic arthritis in rabbits (16 with arthritis and 15 controls) was investigated. After 40 days of treatment with D-penicillamine (intravenous) the arthritis had receded to a large extent. At the same time a maturation inhibition of the hematopoietic marrow had occurred in all the treated arthritic and control animals. The results suggest that D-penicillamine affects fast proliferating cells, to which the precursors of immunologically active cells in the synovial membrane also belong.


[FAB immunoglobulin fragments. I. The comparative characteristics of the serological and virus-neutralizing properties of a gamma globulin against tick-borne encephalitis and of the FAB fragments isolated from it]. A comparative study was made of the serological properties and virus-neutralizing activity of antiencephalitis gamma-globulin and Fab-fragments isolated from it by gel-filtration. Horse immunoglobulins against the autumno-summer tick-borne encephalitis virus could be disintegrated with the aid of papaine to monovalent Fab-fragments which (according to the complement fixation reaction, the test of suppression of the complement fixation, and the HAIT) retained the serological activity whose level was compared with that of the serological activity of gamma-globulin. Fab-fragments possessed a marked virus-neutralizing activity. The mean value of a logarithm of the neutralization index was 2.65 +/- 0.2 for Fab-fragments and 3.74 +/- 0.38 for gamma-globulin (P less than 0.01).


Intestinal absorption of L-tryptophan in scleroderma. The purpose of this investigation was to study the intestinal absorption of L-tryptophan and to assess the absorptive function of the intestine in scleroderma. The oral L-tryptophan loading test was performed in 31 cases of systemic scleroderma (progressive systemic sclerosis, PSS) and 3 cases of localized scleroderma. Serum levels of tryptophan and urinary excretion of indole-acetic acid (IAA) and indican (IS) were determined in order to assess intestinal absorption of tryptophan. In 10 cases the D-xylose test and in 4 cases Schilling's test was also performed. Furthermore, in vitro binding of L-tryptophan by plasma proteins in PSS and in other skin diseases as controls was studied. The normal increase in serum tryptophan after loading was noted in 17 cases (in 14 cases of PSS with a mild, slow progression in 3 cases of PSS with a severe, rapidly progressing course). In 10 of these cases, urinary excretion of IAA was higher than normal and in normal and in 3 cases excretion of urinary IS was also above normal. On the other hand, in 14 cases of severe, rapidly progressing PSS and in 2 of 3 cases of widespread linear scleroderma, serum levels of tryptophan were markedly depressed after loading, while urinary excretion of IAA and IS was normal. In all 4 cases studied, Schilling's test was normal, and only in 2 of 10 cases of PSS was the D-xylose test abnormal. It is concluded that in the majority of cases of PSS, intestinal absorpiton of tryptophan is normal as also is the absorptive function of the intestine. The slight rise in serum tryptophan after loading in some cases of PSS may be a result of increased binding of tryptophan by albumin.


Study of some minerals in scalp hair and blood sera of psoriatics. Scalp hair and blood sera of two groups of psoriatic individuals were examined regarding some of their mineral contents by flame photometric and colorimetric procedures, and the findings compared with a normal control group. The result obtained revealed changes in the mineral content of scalp hair of psoriatics. A possible relationship may exist between hair and serum minerals.


Histiocytosis X with skin lesions as the sole clinical expression. The case is presented of a patient with histiocytosis X of the skin of some 25 years' duration. Extensive investigation failed to reveal any other signs of the disease in other organs. The light and electron microscope findings are described. The electron microscope study revealed an abundant cytoplasm with numerous mitochondria, vacuoles, dense bodies, a well-developed Golgi apparatus and numerous Langerhans' cell granules.


Study of elastolytic activity Propionibacterium acnes and Staphylococcus epidermis in acne vulgaris and in normal skin. Histopathological sections of anetoderma-like scars from 10 patients with acne vulgaris showed a selective absence of elastic fibers around pilosebaceous follicles. This finding is similar to the histologic changes of "perifollicular elastolysis" reported by Varadi. Bacteria isolated by anaerobic and aerobic cultures of swabs of the skin surface and pus of these 10 patients, 12 others with active acne vulgaris and 8 normal subjects were studied with particular attention to Staphylococcus epidermis and Propionibacterium acnes. These organisms were analysed for production of an elastolytic enzyme which might play a role in the observed selective loss of elastic fibers. No elastolytic activity was produced by S. epidermidis or P. acnes isolated from any of these individuals. Thus, we cannot attribute the perifollicular loss of elastic fibers in acne scarring to an elastase produced by organisms. The observed absence of elastic fibers might result from tissue necrosis produced by leukocytes during the inflammatory phase, followed by collagenous scar formation without regeneration of elastic fibers.


An evaluation of delayed hypersensitivity in guinea pigs to various trichophytin preparations. Guinea pigs immunized with mycelium from Trichophyton mentagrophytes in Freund's complete adjuvant were tested intradermally with the following trichophytin preparations: TrI extracted by ethylene glycol, TrII extracted by phenol and TrII, a commercially obtained preparation fromSächsisches Serumverk KG. In our experience, TrI was found to be superior to the other preparations. It showed signifiicant delayed skin reactions in all sensitized animals and none in the controls. Lymphocyte stimulation test with this preparation (TrI) gave positive results.


Plasma concentrations of griseofulvin in healthy volunteers and out-patients treated for onychomycosis. Therapeutic failure of griseofulvin therapy are fairly common, espcially when toe nail infections are treated. The reasons for the failures remain largely unknown. The aim of the present investigation was to study whether pharmacokinetic factors may be responsible. At first, single-dose and steady-state pharmacokinetics of griseofulvin were analysed in volunteers by means of a gas-chromatographic technique. It was found that there was no difference in plasma levels of the three brands of griseofulvin commercially available in Sweden, whereas there was a singificant difference of absorption between individuals. The plasma half-life varied considerably from day to day in the same individual. In the second part of the investigation griseofulvin plasma concentrations were determined in 27 patients treated with griseofulvin for onychomycosis and related to the therapeutic result. All patients but one were initially improved but the therapeutic effect faded in 15 patients after 5-20 months of treatment ("partially healed" patients). In 11 patients the nail infections were clinically healed after 6-24 months. However, no statistically significant difference of the plasma griseofilvin levels could be demonstrated between the healed and partially healed groups. Some possible reasons for the therapeutic failure are discussed.


5-Fluoro-uracil cream in the successful treatment of therapeutically refractory condylomata acuminata of the urinary meatus. A therapeutic trial of 5% 5-Fluoro-uracil in cream form was conducted in 40 men with condylomata acuminata unresponsive to other therapeutic measures. Sixty per cent of the condylomata on the genital and/or anal mucosa showed complete regression. The most promising results were recorded in the cases of condylomata affecting the urinary meatus. These lesions disappeared in 13 of 14 cases after an average of 3 weeks' treatment with subjectively few side effects. With regard to this type of condylomata it may be said that a great therapeutical advance has been achieved. The treatment of other condylomata involving the genital or anal mucosa often causes intolerable discomfort to the patients. The method should in these cases therefore be attempted only when the lesions prove to be refractory to other methods of treatment. In its present form the application of 5-FU cream is difficult to confine solely to the condylomata itself. The cream appears to have little or no effect on condylomata at sites other than the mucosa.


Miconazole in the treatment of candidiasis of the digestive tract. Miconazole nitrate tablets were used in the treatment of candidiasis of the oral cavity and the digestive tract. In 5 out of 6 patients with severe, predisposing factors and who had received previous unsuccessful antimycotic therapy, clinical improvement occurred after a few days of miconazole treatment. Mycological cure of these 5 patients was achieved after 1-11 weeks of treatment. Three of the 5 cured patients relapsed after 3 months, due to basic failure. One patient complained of the drug's unpleasant taste. Otherwise, no side effects were observed. There was no apparent development of any resistance to the drug.


Metronidazole and acne.

Metronidazole and acne. The strong activity of metroindazole against obligate anaerobes suggested that the organism Proprionobacterium acnes and the disease acne vulgaris might respond to treatment with this drug. Thirty-three clinical isolated of P. acnes were tested and found to be highly resistant to metronidazole. Prospects for its successful use in acne are remote.


Comparison of desoximetasone and hydrocortisone butyrate in psoriasis. Thirty psoriatics were treated for 2 weeks on a double-blind controlled basis with desoximetasone (0.25%) and with hydrocortisone butyrate (0.1%). It was a randomised left-right comparative trial. Thirteen out of 27 patients preferred desoximetasone, 3 patients preferred hydrocortisone butyrate. There was also a significantly better effect of desoximetasone as judged by the observer after the second week of treatment.


Bullous pyoderma gangrenosum in association with myeloid leukaemia. The case is presented of a patient with busulfan (Myleran) treated myeloid leukaemia, who developed bullous pyoderma gangrenosum. Skin symptoms appeared at the time when treatment was discontinued due to signs of bone marrow depression. The pyoderma disappeared following treatment with systemic steroid.


The serum protein profile in chronic hepatitis, cirrhosis and liver cancer. Using the single radial immunodiffusion method, the serum levels of IgG, IgA, Ig M, transferrin, haptoglobin, alpha2-macroglobulin, alpha1-antitrypsin and alpha1-acid glycoprotein were estimated in healthy subjects and patients with liver diseases consisting of chronic active and inactive hepatitis, incipient cirrhosis, cirrhosis and primary liver cancer. The results obtained from the statistical analysis of the data were as follows: i) Immunoglobulins and alpha2-macroglobulin in all diseases were higher than those of healthy subjects. ii) The increased transferrin levels were found in chronic active and inactive hepatitis, and the increased alpha1-antitrypsin levels were observed in chronic inactive hepatitis, in incipient cirrhosis in cirrhosis and in primary liver cancer was higher than those of the other liver diseases. iii) Haptoglobulin levels in all diseases except for chronic inactive hepatitis were decreased. iv) alpha1-acid glycoprotein in chronic active hepatitis, in incipient cirrhosis and in cirrhosis were lower than that of healthy subjects. The evaluation of significance for difference of each protein level among disease groups clarified that the decrease of haptoglobin in cirrhosis and the increase of alpha1-antitrypsin in primary liver cancer were characteristic change respectively.


Action of anti-mouse IgE on mouse and rat mast cells. The action of anti-mouse IgE on normal or sensitized mouse and rat peritoneal mast cells as well as on the reaginic activity of mouse and rat antisera was studied. Anti-mouse IgE induced histamine release from normal mouse peritoneal mast cells in vitro and this effect was greatly enhanced when mast cells were actively sensitized. The action of anti-mouse IgE on normal rat peritoneal mast cells was slight; it was enhanced after sensitization of these cells with mouse reaginic antibodies as well as after active sensitization. Moreover, anti-mouse IgE is able to neutralise the reaginic activity of mouse and rat antisera. The results suggest that there exist some functional and structural similarities between mouse and rat IgE.


Calcified inclusions in the superficial pineal gland of the mongolian gerbil, Meriones unguiculatus. A histological and histochemical study of the pineal gland of neonatal, juvenile and adult gerbils is described. Calcified inclusions appear within pinealocytes in the superficial pineal about the third week of age, and the incidence of inclusions increased with age until, by the eleventh week, they are found in all animals. The inclusions contain an organic matrix composed of a carbohydrate, probably an acid mucopolysaccharide, complexed to protein. Calcification does not occur in the deep pineal. The data are interpreted to indicate that the formation of calcified inclusions is a normal process within the gerbil pineal. The similarity of the process of calcification in the gerbil and in the human pineal suggests that the gerbil may be an animal of choice for the controlled study of the phenomenon of pineal calcification.


A morphologically different type of smooth muscle cell in the inner media of the splenic artery. A morphologically different cell type to the typically smooth muscle cell has been found in the inner medial layers of the splenic artery. Besides the morphological differences, typical criteria for a smooth muscle cell are demonstrated, giving an account of their identity. Morphological details are described. The importance of these cells as regards lesions of the vessel wall is briefly discussed.


Diabetic retinopathy. A clinical and morphological study. Twenty retinas of diabetic patients and 10 retinas of non-diabetic controls were examined histologically and the findings correlated to clinical conditions. In the whole mounts of retinas the relationship of vascular and nervous changes could easily be followed. The results demonstrate that retinal changes in diabetes are more frequent than would be expected from ophthalmoscopic exploration.


Potentiation of anaphylactic histamine release from isolated rat pleural mast cells by rat serum phospholipids. Isolation of sensitized rat mast cells by density gradient centrifugation in Ficoll decreases the histamine release obtained when they are subsequently exposed to antigen. The histamine release from such isolated cells is potentiated by the addition of 2% boiled rat serum. This potentiation is dose-dependent and has a temperature optimum of about 25 degrees C. The potentiating activity was localized to the serum phospholipid fraction. Of the pure phospholipids studies (LPC, PC, PE, PI, PS and SM) only phosphatidylserine and lysophosphatidylcholine were found to potentiate the histamine release. The mechanism behind this potentiation is discussed and it is suggested that the potentiation by phosphatidylserine and lysophosphatidylcholine is due to a requirement of these phospholipids for the ion exchange (Na+, K+ and Ca++) or the adenylcyclase activity essential for the histamine release process.


Growth and remodeling of bone. An investigation in chicken with special reference to the mechanism of bone resorption. Bone resorption was studied in chicken by means of histologic and microradiographic examination after intravital injections of three boneseeking fluorochromes. The fluorochromes were injected at intervals from 36 hours to 5 days, and the chicken were killed at 36 hours to 10 days after injection of the third fluorochrome. Signs of osteolysis, such as enlarged osteocyte lacunae surrounded by a metachromatic zone in toluidine blue stained sections, and confluence of osteocyte lacunae in microradiographs, were compared with the fluorochrome labelling pattern. There was no correlation between the histologic findings of osteolysis and the fluorochrome resorption pattern which indicated that existence of so-called bone flow. In the "haversian systems" at midshaft level, the color pattern remained unchanged till resorption took place from the endosteal side. Osteoclasia seemed to be the dominant mode of resorption. The conclusion was drawn that bone flow does not exist in the tibiae of chicken.


Clostridium difficile.

Clostridium difficile. Seventy-five meconium samples were examined for the presence of Cl. difficile; 3 strains were isolated. Additionally 45 laboratory animal faeces specimens were tested for the same purpose, a further 2 cases were isolated. These five suspicious strains were identified as Cl. difficle according to the tests mentioned in the previous paragraphs. The organisms isolated here showed the same characteristics as five of the strains received and also as the organisms isolated from the inoculated animals with the crude cultures of Cl. difficile. These organisms were variable in size, roughly 2-9 XO.3-0. 8u, Gram positive rods, motile, capsulated, flagellated, most probably peritrichous, possessing non-bulging spores located terminally or subterminally, free spores were rarely detectable. Cell arrangements: singly or in pairs and occasionally in short chains. On longer incubation the organisms slightly shifted to become Gram variable and longer in size. Colonies on ordinary agar and solid blood agar appeared to be punctiform and rough. On the other hand the colony appearance on the rest of the solid media which are mentioned previously are as follows: 1-3 mm in diameter, greenish, smooth, non-haemolytic, entire some showing slight irregularities of their edges. Colonies slightly raised, butyrous and semi opaque to opaque. This organism does not liquify the serum of Loeffler medium and also does not cause any changes of this medium. The metachromatic granules are readily seen by Albert's staining. Neither proteolytic nor lipolytic activities are possessed by this organism. Sensitivity to antibiotics showed the same pattern as mentioned about the strains received.


[Changes of serum proteins after craniocerebral trauma - comparison of alpha 2 and alpha 2M (author's transl)]. Quantitive estimations of serum proteins, including Alpha 2M globulin, from 34 patients suffering from craniocerbral trauma have been carried out. The mean value curves over a period of two weeks following trauma are presented graphically. After severe injuries, depending on the size of the cerebral lesions, an increase in Alpha 2 of prognostic significance has been observed. Levels of Alpha 2M do not correlate directly with Alpha 2 globulin, and tend to fall initially. Falls in the first three days after injury may be prognostically significant from the point of view of the prediction of a lethal outcome. There are no significant changes in the levels of total protein, albumin, Beta globulin or Gamma globulin, but Alpha 1 globulin follows the curve of Alpha 2, although to a less marked degree. Correlations between serum protease activites and increases in Alpha 2 due to enzymatically active complexes are unconnected with Alpha 2M, a decrease in which indicates increased inhibitor activity and exhaustion of the inhibitor system.


The role of the acute phase reaction in inflammation. Inflammation and injury to tissue results in a variety of local and systemic events, however although the local events of oedema formation and cellular infiltration have received considerably more attention the systemic response to inflammation is no less profound. The particular systemic event which forms the substance of this communication is the change in the circulating levels of plasma proteins which occurs after inflammatory injury, and the manner in which these changes in plasma concentration are controlled by changes in plasma concentration are controlled by changes in the rate of synthesis. A discussion of the role of the liver in controlling inflammatory events, in relation to the synthesis of an anti-inflammatory protein has been given; the present work is an extension of this and describes the changes in concentration and synthesis rate of albumin, fibrinogen and alpha1 acid glycoprotein during adjuvant arthritis in the rat. The changes which occur are regulated at the liver by alteration of the rate of synthesis of the individual protein. For example albumin at the height of adjuvant arthritis falls to a third of its normal plasma level whereas the level of alpha1 acid glycoprotein increases up to twenty-fold; these changes are reflected by similar changes in their synthesis rate by the liver. The effect of the fall in albumin concentration on the plasma binding of anti-inflammatory drugs (and their toxicity) in relation to these findings will be discussed along with the biological role of the acute phase plasma proteins and hence the influence of the liver in the response to injury.


Immunological and non-immunological mechanisms of some of the desirable and undesirable effects of anti-inflammatory and analgesic drugs. Studies were carried out on patients with adverse reactions to aspirin, paracetamol, phenacetin, codeine, dihydrocodeine, some pyrazolone derivatives, and indomethacin. Three clinico-pathological forms of adverse reactions received particular attention: (1) Asthma, with or without manifestations of systemic anaphylaxis; (2) Serum-sickness-like syndrome; (3) Lymph node enlargement with histological features simulating lymphoma or Hodgkin's disease, which occurred in patients receiving phenylbutazone in particular. A variety of immunological investigations, including some in vitro correlates of immediate- or delayed-type allergy, were carried out. The three syndromes seemed to be associated with immediate-type (or immediate-type-like), immediate-type plus delayed-type, and delayed-type allergy, respectively. In most of the patients with immediate-type-like reactions, and where immunological mechanisms were apparently not involved, pharmacological mediators, particularly histamine, were released from their leucocytes when challenged in vitro with the causative agent(s). This suggested that the main underlying abnormality of their asthma or peripheral vascular manifestations was a direct release of mediators by the drugs, i.e. some type of idiosyncrasy. The causative mechanism of this abnormality has not been established yet.


Tricuspid atresia: results of treatment in 160 children. Experience in managing 160 patients with tricuspid atresia is reviewed. The majority of these children require operative treatment in the 1st year of life. Clinical management of this rather complex anomaly is simplified by classifying each child according to total pulmonary blood flow. An overall plan of management for patients with decreased pulmonary flow is suggested. This consists of a Potts shunt as an initial procedure, limiting its anastomotic growth so that pulmonary flow becomes inadequate at age 10 to 12 years. A Glenn anastomosis is then constructed as the second procedue. The Fontan procedure should be considered carefully as an alternative to the Glenn anastomosis in these older children. Children with increased pulmonary blood flow and transposition of the great arteries are likely to require pulmonary arterial banding in infancy. Otherwise, patients in this smaller group are managed with the same overall plan. Results of long-term palliation have been good.


Elastic fiber formation in monolayer and organ cultures of chondrocytes isolated from auricular cartilage. Chondrocytes were isolated from auricular cartilage of immature rabbits and maintained in monolayer or organ culture for 14 days. In both types of culture the chondrocytes formed conspicuous elastic fibers. In monolayer culture the fibers could be identified by orcein staining in the culture dish. Electron microscopy of organ cultures revealed the presence of two basic components of elastic fibers, i.e. microfibrils and elastin.


Tannic acid as an electron-dense probe in the testis. The use of tannic acid to preserve and promote the staining of protein constituents of the extracellular fluid is described. Its usefulness for delineating the extracellular compartment and detecting changes in capillary permeability is illustrated in experiments on the testis.


Gastric carcinoid following gastrojejunostomy. A carcinoid tumor of the gastric body was found in a patient who had a gastrojejunostomy done for duodenal ulcer 36 years earlier. Association of gastric carcinoid with gastrojejunostomy has previously been described by Lemmer. In contrast, such tumors have never been observed when the more common surgical procedure for peptic ulcer was used, ie, gastric resection. On the basis of recent knowledge on gastric endocrine cells, the authors suggest a relationship between the gastrojejunostomy and the carcinoid tumor, probably related to an elevated gastrin release.


Quantitation of antibodies to Herpes simplex virus types 1 and 2 by complement-dependent antibody lysis of infected cells. The release of 51Cr from cells infected with herpes simplex virus type 1 or type 2 by antibody and complement was examined as a method of quantitating antibodies to the viruses. With decreasing concentration of antibody, a typical dose-response curve was observed; a region of antibody excess in which dilution did not affect percentage of specific 51Cr release followed by a region in which a linear relation existed between dilution and percentage of specific 51Cr release. Therefore, a quantitative expression of antibody titer was defined as that dilution of serum which yielded 50% specific 51Cr release. The slopes of the linear portion of the dose-response curves were characteristic of the type of virus used to infect the cells and not upon the source of antiserum, thus, the slopes could be used to estimate antibody titers. The multiplicity of infection influenced the antibody titers; reproducible results were obtained when cultures were infected with 3 to 5 plaque-forming units per cell; the antibody titers decreased when less virus was used. The antibody titers obtained by the 51Cr release test were similar to those obtained by a microneutralization test. The 51Cr release test was found to be reproducible and to be useful in estimating the percentages of antibody activity attributable to antibodies to cross-reacting and type-specific antigens.


Relative concentrations in human sera of antibodies to cross-reacting and specific antigens of Herpes simplex virus types 1 and 2. The relative concentrations of antibodies to the cross-reacting and type-specific antigens of herpes simplex virus types 1 and 2 were examined in sera from patients who had been infected by type 1 virus only, by type 2 virus only or by both viruses. Complement-dependent lysis of 51Cr-labeled cells was used to measure antibodies to the surface antigens of cells infected by the viruses. Approximately 80% of the antibody activity was attributable to cross-reacting antigens and 20% to type-specific antigens in sera from patients infected with either type 1 or type 2 virus. Among patients infected with type 1 virus and then type 2 virus, approximately 90% of the antibody activity was to the cross-reacting antigens, 5 to 10% to type 1-specific antigens and little or no antibody to type 2-specific antigens. The observations suggest that infection by type 2 virus in patients with a prior type 1 infection results in an antibody response to the cross-reacting antigens with little or no response to the type-specific antigens.


The frequency of chromosome aberrations in tall men with special reference to 47, XYY and 47, XXY. All men born during the years 1944-1947 to mothers who were inhabitants of Copenhagen when they gave birth, were identified. The adult heights of all but 2,552 of these 31,438 men were obtained; a group of 4,591 men at least 184 cm tall were selected for examination. Samples for chromosome studies were obtained from 4,139 (90.2%) of these tall men. A total of 41 (1%) abnormalities were identified (33 sex chromosome abnormalities, including 12 XYYs (0.3%) and 16 XXYs (0.4%), 6 autosomal abnormalities, and two of uncertain origin). The XYY and XXY groups were taller than the selected sample of tall XY men.


The segregation of C-band polymorphisms on chromosomes 1, 9, and 16. Eleven normal families with at least four children were studied cytogenetically using the C-band technique to identify polymorphisms in the constitutive heterochromatin of chromosomes 1, 9 and 16. Thirteen individuals showed one or more variants in such chromosomes. The analysis of the segregation ratios in the 35 offspring of these 13 individuals showed that these marker chromosomes generally segregated according to the expected 50:50. However, one of these variants, chromosome no. 9 with an increased heterochromatin block in the secondary constriction, has an apparently preferential segregation, when the findings from this study are combined with those of other authors.


Methenamine-silver-stained corneal scrapings in keratomycosis. A shortened version of Grocott's methenamine-silver technique for use in staining corneal scrapings was superior to current methods for the diagnosis of mycotic keratitis.


Current practices in evaluating motor behavior of disabled children. Current practices in evaluating motor behavior were studied in a sample of facilities providing services to children in the United States and Canada. Two hundred and fifty-six supposedly different published and unpublished tests were reported in use by a variety of disciplines. Respondents reported dissatisfaction with many of the tests and also indicated a general pattern of misusing the tests in relation to the disability groups and age ranges for whom the tests were developed. Results are discussed in relation to the need for an interdisciplinary approach to knowledge development and personnel preparation in the area of motor evaluation.


Pseudoobstruction in ceroidosis.

Pseudoobstruction in ceroidosis. Diffuse deposition of ceroid pigment in the muscularis propria of the gastrointestinal tract in a patient with a long history of malabsorption of unknown origin is reported. The depostion of this waste pigment is not reversible and is related to prolonged depletion of vitamin E. Progressive dilatation and hypomotility of the entire gastrointestinal tract are demonstrated by radiographic studies and possibly related to infiltrate of ceroid pigment in the smooth muscle cell with resulting functional impairment. In the differential diagnosis of ceroidosis with other disease, scleroderma has the closest roentgenographic similarity. Pseudoobstruction of the small bowel which can develop must be treated conservatively to avoid unnecessary bowel resection.


[The influence of different plasma substitutes on blood clotting and platelet function during and after operations (author's transl)]. It has been shown in clinical experiments that plasma substitutes generally have a specific-colloidal influence on special parts of the clotting system. These changes are predominant after infusion of dextran, since on one hand there is an inhibition of platelet function, and on the other hand a decrease in the activity of plasmatic clotting factors. It is to be emphasized that hydroxyethyl starch and with some restrictions even gelatins cause a comparable inhibition of platelet function. These reactions are due to colloid-specific effects only, which have been unknown up to now. Activities of plasmatic clotting factors, however, are not influenced by these substitutes.


Improved staining method for differentiating immature germ cells from white blood cells in human seminal fluid. A new staining method for differentiating WBCs from immature germ cells in seminal fluid has been studied. It is a combination of Bryan's sperm stain, which particulary stains the acrosomal cap of the spermatozoa and the spermatid, and Leishman's blood stain which stains the WBCs in the same way as found in blood smears. The peroxidase positive granules in the cytoplasm of the PMN leukocytes are seen clearly. Thus, it is possible to differentiate PMN leukocytes from non-separated spermatids when they are present in a common cytoplasm. The staining of acrosomal cap permits differentiation between spermatids and lymphocytes.


Production of an equine anti-bovine leukocyte serum. A method is described for production of an equine anti-bovine leukocyte serum (EABLS). Leukocytes were harvested from the milk of cow's udders which had been irritated with endotoxin. The washed leukocytes as antigens were administered to 2 horses in a series of subcutaneous and intravenous injections. There was a variably progressive increase in total serum proteins and a decrease in albumin/blobulin ratios, but the most pronounced change was an increase in beta2-globulins. Accompanying these changes was an increase in the number of precipitin lines as shown by Ouchterlony analysis. Four old cows and 2 calves were intravenously given a 50- and 20-ml dose, respectively, of the EABLS. Two of the cows and 1 of the calves were given the EABLS which had been heated to 56 C for 30 minutes. Both calves and the 2 cows given heated EABLS and 1 cow given unheated EABLS developed marked neutropenia within the 1st hour. The 4th cow given unheated EABLS developed only slight neutropenia. It was concluded that there may be variation in the individual animal's susceptibility to the neutropenia-inducing activity of EABLS.


Immunocompetent cells of the turkey: antigenic surface determinants of turkey lymphoid cells. The serologic properties of chicken antiserums to turkey bursa and thymus were assayed by the cytotoxicity tests and indirect immunofluorescence. The following antigenic surface determinants were detected, using proper absorptions on thymic and bursal lymphoic cells: (a) common lymphocyte antigens present on both kinds of cells, (b) thymus-specific antigens, (c) bursa-specific antigens, and (d) immunoglobulin surface determinants in bursa cells, as revealed by direct immunofluorescence.


5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.


Anaphylaxis: etiology and guidelines for management. The successful management of anaphylaxis requires a thorough understanding of this syndrome and the application of various therapeutic agents. Although the mechanisms responsible for human anaphylaxis are not fully known, sufficient data and clinical experience are available to guide the anesthesiologist faced with this medical emergency.


[Comparative study "in vitro" between rabies and rabies related viruses by the sensitized lymphocytes technique]. Rabbit lymphocytes obtained from animals previously exposed to rabies virus undergo a specific lymphoblastic transformation when incubated in vitro in the presence of either the complete virus or a nucleocapsid fraction. This type of in vitro transformation was observed by the Pasteur, Lagos, Mokola, Obodhiang viruses as well as the virus HEP in cells originally exposed only to the virus HEP. In additions to the morphological changes of lymphoblastic transformation, 3H-thymidine incorporation was stimulated about 21 to 67 fold in homologous system and about 6 to 39 in heterologous systems and unrelated with other virus system like influenza. These results suggest an immunological relationship between the classic rabies strains (HEP, Pasteur) and subgroup rhabdovirus (Lagos, Mokola, Obodhiang).


Primary carcinoma of the liver.

Primary carcinoma of the liver. Primary carcinoma of the liver is rare in Western countries but it is a common malignant tumour in many parts of the tropics. Much has been learnt in recent years about its pathology, manifestations, and aetiology that is relevant to the whole field of oncology. The important distinction between carcinomas of liver-cell and bile-duct origin, the phenomenon of alpha-fetoprotein production, and the role of cirrhosis are discussed in the context of newly discovered aetiological factors such as gonadal steroids, mycotoxins, and the hepatitis B virus.


[Contribution to the antigenic study of influenza viruses in animals. I.--Neuraminidase of the equine influenza viruses (author's transl)]. From the Revised Nomenclature of WHO, the fowl influenza virus A/Duck/Ukraine/63 (Hav7 Neq2) has the same neuraminidase as the equine virus A/equi 2/Miami/63 (Heq2 Neq2); the A/Chicken Germany "N"/49 virus has the same neuraminidase as the equine virus A/equi 1/Prague/56. A comparative study of the antigenic specificities confirms that the Neq2 neuraminidases are closely connected, whatever their animal origin, and that the fowl strain Hav7 Neq2 can be used for the titration of anti Neq2 antibodies in the serums of animals immunized with the equine virus Heq2 Neq2. The Neqi neuraminidases of various animal origins are connected, but the neuraminidase of the fowl strain Hav2 Neqi is slightly inhibited by the anti Neq1 antibodies of animals immunized with the Heq1 Neq1 virus: to titrate the anti Neq1 antibodies of equine origin, the H72 Neq1 recombinant should therefore be used. The antigenic characterization of the different equine influenza strains isolated since 1967 by the study of their neuraminidase has been completed: The various neuraminidases, like the hemagglutinins of the various strains belonging to the sub-type A equi2 are closely connected; a minor antigenic variation, concerning the two surface antigens, seems to exist between the strain A equi 1/Prague/56 and the strain of the same subtype isolated in 1973.