Home haemodialysis in children. Report of the London Children's Home Dialysis Group. In January, 1973, a study was established to evaluate, prospectively and independently, the growth and psychosocial adaptation of children in end-stage renal failure treated by home haemodialysis at Guy's Hospital and the Royal Free Hospital. By January, 1975, 26 children had entered the study, but 2 died before they were established on home haemodialysis. In this paper a specified 1-yr period starting 6 mo after the onset of haemodialysis was selected for analysis. School attendance, diet, plasma-biochemistry, bone disease, growth, and emotional symptoms were investigated in each child. Rehabilitation was satisfactory, and average school attendance was 65%. Growth in all the prepubertal children was poor, whereas in most pubertal children it was adequate. At the end of the year, only 5 children were emotionally disturbed, but half the families had stress symptoms. The children at Guy's Hospital were dialysed more intensively than those at the Royal Free Hospital, and they had significantly lower mean plasma urea and creatinine concentrations and a greater energy and protein intake. On the other hand, the children at the Royal Free Hospital had a better school attendance. We conclude that home haemodialysis is an acceptable treatment for children in end-stage renal failure.


Prenatal diagnosis of beta-thalassaemia and sickle-cell anaemia. Experience with 24 cases. Prenatal diagnosis of beta-thalassaemia and sickle-cell anaemia was attempted in 24 pregnancies. Adequate amounts of fetal blood (for studying globin-chain synthesis) were obtained in 22 cases. 4 cases of homozygous beta-thalassaemia and 2 of sickle-cell anaemia were diagnosed. The difference between the homozygous and non-homozygous states was well defined. Fetal bleeding from cord puncture and amnionitis resulted in the loss of three fetuses, and methods to avoid these complications are being devised. It is concluded that prenatal diagnosis of disorders of beta-globin synthesis is feasible.


Evaluation of beta blockade bendrofluazide, and prazosin in severe hypertension. 20 patients with severe essential hypertension (average blood-pressure 211/123 mm Hg) had an inadequate fall in blood-pressure with beta blockade alone. They were given in random order either 5 and then 10 mg of bendrofluazide a day or prazosin 2 mg three times daily rising to 5 mg if required. The trial was a within-patient comparison of the two drug regimens. 10 patients who did not achieve a satisfactory fall in pressure with either agent were then given all three drugs together. When bendrofluazide 5 or 10 mg was added to beta blockade there was an average fall in mean blood-pressure, standing, of 13%. When prazosin was added to beta blockade the average fall in mean blood-pressure, standing, was 16%. 18 patients who completed the trial had an average final blood-pressure, standing, of 139/93 mm Hg. In the prazosin period 8 patients continued to complain of dizziness after the first 24 h. With bendrofluazide serum-potassium levels fell below 3-6 mmol/l in half the patients within the first two weeks of treatment. It is concluded that patients with essential hypertension already treated with beta blockade who need an additional agent will get a further fall in blood-pressure with 5 mg of bendrofluazide. Prazosin appears to be a potent and appropriate third agent.


Soybean-protein diet in the treatment of type-II hyperlipoproteinaemia. A soybean textured protein induced a 14% decrease of plasma-cholesterol levels after two weeks and 21% after three when substituted for animal proteins in a group of 20 patients with type-II hyperlipoproteinaemia. Comparison of soybean diet with a standard low-lipid diet in the same patients, according to a cross-over protocol, indicated that this hypocholesterolaemic effect was not due to differences in the lipid composition of the two diets. The hypothesis that a soy protein has a hypocholesterolaemic action per se is supported by the results of a subsequent experiment in 8 type-II patients in whom the addition of cholesterol (500 mg/day) to soy protein did not modify the hypocholesterolaemic response.


Relation between endemic (Balkan) nephropathy and urinary-tract tumours. Serum and urine beta 2-microglobulin concentrations were determined in 38-6% of the 869 inhabitants of a village in which both Balkan endemic nephropathy and papillary tumours of the urinary-tract epithelium are common. Over 23% of the "healthy" population had raised serum and/or urine beta 2-microglobulin. 5 of 6 patients with papillary tumours of the renal pelvis, without evidence of renal parenchymal involvement, and 13-4% of the "healthy" population had raised serum-beta 2-microglobulin. It is suggested that overproduction of beta 2-microglobulin, a light-chain-like immune globulin, by the tumour cells may result in a light-chain-like nephropathy--i.e., endemic Balkan nephropathy.


Reversible insensitivity to androgens in men with untreated gluten enteropathy. Plasma androgen and gonadotrophin concentrations have been measured before and during treatment of 23 men with gluten enteropathy. Before treatment, there was marked rise in total plasma-testosterone, free testosterone concentration (as assessed by the free testosterone index), and plasma-luteinising-hormone concentration. In contrast, 5 alpha-dihydrotestosterone concentrations were lower than normal. All these abnormalities reverted towards normal with successful treatment of the jejunal mucosal lesion. These data are consistent with a reversible tissue resistance to circulating plasma-testosterone in men with gluten enteropathy and subtotal villous atrophy.


Magnesium therapy in neonatal tetany.

Magnesium therapy in neonatal tetany. 104 infants with symptomatic hypocalcaemia were randomly allocated to treatment with calcium gluconate, phenobarbitone, or magnesium sulphate. Infants treated with magnesium sulphate had higher plasma-calcium concentrations after 48 hours' treatment and fewer convulsions during and after the treatment period. Magnesium sulphate is recommended as the treatment of choice in symptomatic neonatal tetany whether or not there is hypomagnesaemia.


Microsurgical tubocornual anastomosis for reversal of sterilisation. 11 of 16 patients had intrauterine pregnancies after microsurgical tubocornual anastomosis for reversal of sterilisation. This procedure has several important advantages over tubal reimplantation and may be of benefit in the treatment of infertile women with inflammatory blockage of the isthmus of the fallopian tube.


An association between abo blood-group distribution and geographical differences in death-rates. In England, Wales, and Scotland there is a strong association between mortality-rates and ABO blood-group distribution. It is suggested that some of the discrepancies in investigations of the relation between water hardness and mortality-rates from cardiovascular disease may be attributed to genetic influences.


Extrinsic allergic alveolitis and contaminated cooling-water in a factory machine. Symptoms and signs typical of extrinsic allergic alveolitis occurred in 24 workers in a stationery factory. The illness was caused by inhalation of a water aerosol contaminated by microorganisms, and although no specific organism has been incriminated, affected workers had serum precipitins to the contaminated water, and the illness could be reproduced by inhalation challenge tests.


Prevention of eczema.

Prevention of eczema. In a prospective study of the development of reaginic allergy, infants of allergic parents were either subjected to an allergen-avoidance regimen from birth for six months or managed conventionally. The group on the allergen-avoidance regimen had less eczema at six months and one year than did the control group at six months. They also had a lower mean serum-total-IgE level at six weeks.


Measles-virus-specific immunoglobulin-M response in subacute sclerosing panencephalitis. Measles-virus specific IgM and IgG responses in sera and cerebrospinal fluid (C.S.F.) of 20 patients with subacute sclerosing panencephalitis (S.S.P.E.) and of two control groups were examined by indirect radioimmunoassay. All S.S.P.E. patients, regardless of the stage of the disease, had high titres of anti-measles antibodies in sera and C.S.F. The antibody activity was associated with both the IgM and the IgG classes of immunoglobulins. In 7 (35%) of the S.S.P.E. cases the specific IgM response was more pronounced in the C.S.F. than in the serum, suggesting IgM production within the central nervous system. The two control groups did not have a specific IgM response in C.S.F. or serum. It is assumed that the continuing release of measles antigen in S.S.P.E., as the result of the persistence of virus virus in the central nervous system, pevents the shut-off of IgM synthesis and is responsible for the specific IgM activity. It is proposed that the detection of virus-specific IgM antibodies in the C.S.F. of patients with chronic diseases of the central nervous system can be taken as an indication of persistence of virus.


Histocompatibility antigens as markers of abnormal iron metabolism in patients with idiopathic haemochromatosis and their relatives. HLA-A3 was significantly more common in 35 unrelated patients with idiopathic haemochromatosis (69%) than in 95 controls (31%). Further studies in two families suggest that 2 genes are involved in the pathogenesis of the disease, each associated with a separate metabolic defect. Whereas minor abnormalities, namely raised serum-iron and some increase in storage iron, were found in relatives with an HLA A11, B27, CW2 haplotype, those with the A3, B14, CW5 haplotype had no detectable abnormalities. When both these haplotypes were found together, as in the propositus and one sibling in the first family investigated, all the signs of the fully developed disease were apparent. It is suggested that one of the genes is in linkage disequilibrium with HLA-A3 and could be responsible for a kinetic abnormality, possibly increased plasma to storage iron exchange. The other gene, also carried on the sixth chromosome and, in the first family, marked by the HLA A11, B27, CW2 haplotype might result in an increased absorption of dietary iron. The concomitant inheritance of these two genes and the metabolic defects they determine are required for the full development of the disease


Impairment of immunity during pregnancy and antiviral effect of amniotic fluid. In 297 pregnant women serum-levels of antibody to rubella virus were determined by haemagglutination inhibition, and serum-levels of antibodies to herpes-simplex virus and Toxoplasma gondii were measured by indirect immunofluorescence tests. Sera of age-matched non-pregnant women with intrauterine devices were also tested for the antibodies. A lower level of humoral immunity was found in the pregnant women than in the controls, and this fell further as pregnancy progressed. Investigation of serum-samples taken at 14 weeks' gestation, at delivery, and 30-45 days post-partum revealed that after delivery humoral immunity to rubella virus returned to the levels of early gestation. Of 44 amniotic-fluid samples collected from pregnancies terminated at 11-14 wk and examined for antiviral activity to herpes-simplex virus and polio-virus, 7 exerted an antiviral effect which could be linked with the protein (other than alpha1-fetoprotein) fraction of the amniotic fluid.


Concentrations of pregnancy-specific beta 1-glycoprotein in maternal blood in normal pregnancy and in intrauterine growth retardation. A radioimmunoassay has been developed for pregnancy-specific beta 1-glycoprotein (S.P.1), a product of the human placenta. Circulating concentrations of S.P.1 were measured in 153 women in the third trimester of normal pregnancy and in 27 women who delivered children with birth-weight below the 10th centile of the normal range--i.e., with intrauterine growth regardation (I.U.G.R.). Concentrations of S.P.1 showed a skewed distribution and rose progressively to reach a plateau in the last four weeks of pregnancy. In over 70% of women with I.U.G.R. of the fetus, concentrations of S.P.1 were low. Measurement of serum-S.P.1 may provide a new index of fetal wellbeing.


Specific and sensitive determination of pregnancy-specific beta 1-glycoprotein by radioimmunoassay. A new pregnancy test. A specific and highly sensitive radioimmunoassay (R.I.A.) for determination of pregnancy-specific beta 1-glycoprotein (S.P.1) in human plasma, urine, amniotic fluid, and breast milk has been developed. The minimum detection limit of S.P.1 was 8 mug/1 of sample. The assay was applied to plasma and/or urine samples from 8 women in early pregnancy. S.P. 1 was detected in the plasma of all three women obtained within 14 days of ovulation, the earliest positive result being at 7 days. In another woman plasma was negative at day 18 and positive by day 22. In the three remaining women plasma S.P.1 was detected when measured within 24 to 36 days of ovulation. S.P.1 was detected in four urine samples obtained between 20 and 28 days after ovulation. S.P.1 was also measured in breast milk, amniotic fluid, cord blood, and plasma of women with ectopic gestation and trophoblastic disease. It is suggested that the assay of S.P.1 may have important advantages over existing systems for detection and monitoring of early pregnancy.


Is Burkitt's lymphoma related to perinatal infection by Epstein-Barr virus? Burkitt's lymphoma (B.L.) is very restricted geographically, whereas the Epstein-Barr virus (E.B.V.), a very likely causal factor, exists all over the world. It is proposed that perinatal infection (either transplacental, or, more probably, neonatal) is an important risk factor for the development of B.L. This hypothesis arose when the epidemiological characteristics of E.B.V. infection were compared in different parts of the world and is supported by the preliminary results of a seroepidemiological prospective study of B.L. E.B.V. would behave in a manner similar to that of animal tumour viruses whose oncogenic potential is greatly enhanced by neonatal infection.


Success and problems of long-term levodopa therapy in Parkinson's disease. The patient with Parkinson' disease on chronic levodopa therapy, like the diabetic on insulin, is dependent on the drug. Like the diabetic, the patients with Parkinson's disease may run into problems during long-term treatment. Two have emerged as frequent and serious, an insidious and progressive loss of benefit and the appearance of progessively more severe fluctuations in disability. It is concluded that progression of the underlying pathology of the disease is probably responsible. Discovery of the exact causes for loss of benefit may provide a rational basis for new therapy.


Obesity in childhood: A community study in Newcastle upon Tyne. All children born of Newcastle upon Tyne mothers in 1960, 1961, and 1962 who were obese at the age of ten years have been investigated. Anthropometric, social, and psychological data were collected from the children and their families. The results confirm that obesity in childhood has many causes. The obesity was of early onset in 43% of the children, the remaining majority becoming obese after the age of five years. The commonest "at-risk" factors were obesity in a first degree relative, an elderly mother, being an only child, and absence of one parent. Two or more of these factors were present in at least 60% of the obese children.


Gene specific priming of complementary DNA synthesis. DNA, complementary to chicken globin mRNA was synthesized using either Avian Myeloblastosis virus reverse transcriptase, or E. coli DNA polymerase I. Transcriptase cDNA sediments at 9 S on sucrose gradients, and is 620 nucleotides in length, representing a complete copy of globin mRNA template. In contrast, Polymerase I cDNA sediments at 4 S, is 100 to 200 nucleotides in length, and is a copy of a small region at the 3'(poly A) end of globin mRNA. Similarly, Transcriptase cDNA and Polymerase I cDNA hybridize to globin mRNA template with characteristic, individual Crot1/2 values. The Crot1/2 value for Transcriptase cDNA hybridization is 7 X 10(-4) mol s 1(-1), and that for Polymerase I cDNA is 5 X 10(-3). This work shows that Avian Myeloblastosis virus reverse transcriptase can use Polymerase I cDNA to prime further cDNA synthesis along the mRNA template. The product of extended cDNA synthesis is identical in length and hybridization properties to oligo (dT) primed transcriptase cDNA.


[Minor diphtheria epidemic in a Cologne children's home (author's transl)]. Between May and July 1972, 12 children aged from 7 to 14 were admitted to the Cologne University Children's Hospital suspected of having diphtheria. In 10 cases the tonsils or pharyngeal cavity were affected. One case of wound diphtheria and one of nasal diphtheria were observed. The clinical suspicion was confirmed in 8 of 12 cases by detection of the pathogen Coryne-bacterium diphtheroides mitis. 11 patients were discharged from the hospital after being treated for between 2 to 6 weeks, but 5 of them needed ambulant cardiac observation. One patient died of malignant diphtheria with symptoms of cardiovascular failure. He had not been treated specifically for 1 week at first. Not one of the 12 patients had been satisfactorily immunized by active inoculation with diphtheria toxoid.


Ten model mutagens evaluated by the micronucleus test. The following ten mutagenic compounds were subjected to the micronucleus bone marrow test (MNT) in the mouse: cyclophosphamide (CTX), thiotepa (TT), vincristin (VCR), colcemid (COLC), adriamycin (AM), bleomycin (BM), cytosin arabinoside (ARA C), 6-mercaptopurine (6-MP), methotrexate (MTX) and 5-fluorouracil (5-FU). Dose-effect curves were established for all compounds. With the exception of CTX, COLC and AM, the drugs also were subjected to chromosome analyses on Chinese hamster fibroblasts in vitro. The MNT revealed loss of chromatin due to chromosome breakage and rearrangements by CTX, TT and AM, to breakage by ARA C, 6-MP, MTX and 5-FU, as well as loss of entire chromosomes caused by impairment of the spindle by VCR and COLC. With the exception of BM, the effects were demonstrable in the therapeutic dose range. The MNT, provided it is carried out by the methodology of the authors, not only reveals chromatin loss but permits important conclusions in regard to the proliferative state of the bone marrow and the specific time of action of the mutagens in the cell cycle. If arrest of the cell cycle occurs, as in the case of anti-metabolites MTX and 5-FU particularly, the routine scheme of investigation needs to be modified since micronucleated cells appear only after release of the metabolic block, i.e. after a delay of 24 h. The negative bone marrow results obtained with BM emphasize the importance of combining in vivo and in vitro tests.


Cytogenetic analysis of human chromosomes and its value for the estimation of genetic risk. A short review of present-day contradictory opinions on the usefulness of human chromosomal analysis in the system of chemical mutagen testing is illustrated by examples of the results achieved by both conventional and banding techniques. The results include exposures of human chromosomes to ECHH and TEPA in vitro, and to ECHH, vinyl chloride and Imuran in vivo. Exposures of human lymphocytes in vitro to the chemical to be tested for mutagenicity are recommended as one of the tests to be included in the system of mutagenicity testing, parallel with all other tests on mammalian and submammalian levels. The testing of human chromosomes of people exposed to chemicals in vivo is considered essential.


Relationship between acute and chronic exposures in mutagenicity studies in mice. The relationship between acute and chronic exposures in mutagenicity studies on mammals still lacks experimental data that might permit the decision whether or not the long-term exposures are of significance mutagenicity testing. Fractional application of TEPA, THIOTEPA, EMS, cyclophosphamide and sodium arsenite was made in experiments with mice, by using the dominant-lethal test and cytogenetic analysis of bone marrow. In most experiments the repeated application yielded the same or higher genetic injury than the same total dose at a single application. Negative results are discussed in relation to the threshold dose and the different sensitivity of the germ-cell stage. Possible interaction of mutagens was also studied by analysing the combined effect of a long-term exposure to sodium arsenite, which probably affected the repair mechanism, and of a single dose of TEPA. It is concluded that the present stage of knowledge requires acceptance of the opinion that the genetic risk induced by chronic exposure to a chemical is as serious as that induced by acute exposure.


Rates, sample sizes, and the neutrality hypothesis for electrophoresis in evolutionary studies. It is shown that electrophoretic genetic distance estimates are highly correlated with albumin immunological distances between the same pairs of species. The bimodality of rates of electrophoretic differentiation at various loci is then documented and the electrophoretic clocks involved are calibrated. The differences between the systematics and population genetics uses of electrophoretic data are then discussed. Finally, a direct electrophoretic test of the neutral alleles hypothesis is presented and exemplified on a set of Thomomys bottae-umbrinus data.


Biodegradation of alpha-hexachlorocyclohexane. VII. Resolution, purification, and characterization of an alpha-HCH dechlorinating enzyme from rat liver cytosol. From rat liver cytosol, an enzyme was isolated which catalyzes the dechlorination of alpha-, gamma-, and delta-HCH. The enzyme also catalyzes the conjugation of GSH with 1,2-dichloro-4-nitrobenzene, and with 1 -chloro-2,4-dinitrobenzene. The enzyme has a molecular weight of about 46000 and its molecule is composed of two subunits of similar size. The optimum for the dechlorination of alpha-HCH lies at pH 8.0. The Michaelis constant is 0.12 mM for alpha-HCH (with 1 mM GSH as constant substrate), and maximal velocity was determined to be 0.25 moles Cl- -min -1 per mole enzyme.


Efferent projection of the nucleus praeopticus medialis to the median eminence in rats. Efferent projection from the medial preoptic nucleus, especially to the median eminence, was studied in the rat by light and electron microscopy, in combination with 3H-leucine labelling and electrical coagulation of the nucleus. In the light microscopy autoradiographs of the brain, an ipsilateral distribution of silver grains was followed caudally and dorsally in the periventricular area, into the triangular area between the ventromedial nucleus and the arcuate nucleus, and, further, into the paraventricular and supraoptic nuclei and median eminence. After electrical coagulation of the medial preoptic area, electron microscopy showed numerous degenerated nerve terminals in the external layer of the median eminence. Occasionally, cored vesicles (90 nm mean diameter with a core of 70 nm mean diameter) and clear vesicles (40-50 nm diameter) were encountered in the axoplasm of the degenerated nerve terminals. These findings indicate that the axons of the nerve cells of the medial preoptic nucleus extend caudally, terminating in the external layer of the median eminence.


Treatment of advanced lymphomas with bleomycin (NSC-125066). 88 patients with far-advanced lymphomatous malignancy were treated with Bleomycin given by either intramuscular (i. m.) or intravenous (i. v.) injection according to a randomized treatment assignment. Response occurred most frequently in Hodgkin's disease (i. m. 7/24; i. v. 4/18), least often in histiocytic lymphomas (i. m. 0/8; i. v. 1/8), and with intermediate frequency in lymphocytic lymphomas (i. m. 3/16; i. v. 0/14). While toxicity was common (70%), severe toxicity was unusual (8%) with severe pulmonary toxicity occurring in four patients (three i.m.; one i.v.). All three drug associated deaths occurred in i. m. patients. Unexpected life-threatening pericarditis occurred in two i. m. treated patients. Although response and drug related deaths occurred more often in the i. m. patients, the comparison with i. v. patients was not statistically different.


A comparative study of five materials for use in filling root canal spaces. The purpose of this study was dual: (1) to test the adaptation of various filling materials to the walls of instrumented root canals and (2) to test which of the experimental materials can be utilized with the pressure syringe. The root canal spaces of 210 extracted permanent anterior teeth were instrumented and, with the pressure syringe, the canals and access cavities were filled with a sealer or cement. Teeth filled with laterally condensed gutta-percha and sealer, and with a silver cone plus laterally condensed gutta-percha and sealer served as the controls. Except for the apical openings, the roots were coated with sticky wax and then placed in methylene blue dye at 37 degrees C. for periods of 1 day, 1 week, and 1 month. The teeth were removed from the dye and sectioned longitudinally, and the length of the dye penetration between the filling and the canal wall was measured. Of all materials tested, the silver point control exhibited the least amount of marginal seepage at each time period. AH-26 exhibited the least amount of marginal seepage after 30 days as compared to the other experimental materials and the gutta-percha control, and was the easiest material to handle of all those tested. Since gutta-percha has been shown to be clinically successful, and since it did not differ significantly in dye seepage from the other materials, all materials tested will give a satisfactory result up to 30 days when used as a root canal sealer under these testing conditions.


[Experiments on the biosynthesis of UDP-Glucuronyltransferase and UDP-Glucosyltransferase under the influence of eucalyptol (author's transl)]. To elucidate the reaction mechanism of the increased elimination rate of bilirubin in the blood of newborns under the influence of Eucalyptol, we performed a study on young mice. The following results were obtained: UDPGA-T activity is increased 33%, if measured with 4-MU as substrate after a single injection (i.p.) of Eucalyptol (0.3 mg/g body weight), with bilirubin as substrate the increase is 112%. UDPG-T activity increases 29%. The enhancement of enzyme activities can be inhibited by Actinomycin D (1 MUg/g body weight) 30% (bilirubin), 48% (4-MU) respectively in the case of UDPGA-T. Under cycloheximide (2 mug/g body weight) the increase of the activity of UDPGA-T is suppressed by 59% (bilirubin) or 99% (4-MU) as compared to the corresponding controls. No significant difference in the activity of UDPG-T by actinomycin or cycloheximide can be observed between the controls and the Eucalyptol-treated group. We conclude that the increase of enzyme activity of UDPGA-T is mainly due to enzyme induction, while in the case of UDPG-T activation of enzyme molecules might be the underlying mechanism. The effect of Eucalyptol on the bilirubin level in the blood of newborns is comparable to the effect of phenobarbital.


[Formation of xanthomatous cells in vitro from the aortic media of the rat]. The foam cell is viewed as a specific component of the atherosclerotic plaque found in human or experimentally induced in the animal. A study using light microscopy (staining with Sudan III) and electron microscopy was performed on cell cultures derived from rat aortic media. Sudanophilic and electron transparent vacuoles were observed in vitro in 11 week cultures. The sudanophilic cells were either scattered or crowded in clusters; some of them were found in a mitotic phase. Different serums were applied to the cultures starting from the 6th week: either calf serum (continuing the previous treatment), or normocholesterolemic rat serum (NCRS) or hypercholesterolemic rat serum (HCRS). Sudanophilic cells were observed more frequently in the cultures on exposure to HCRS than to NCRS (p less than 0.05). Thus it was possible to induce the formation of foam cells in vitro in cultures of arterial tissue derived from the rat, which is known to be resistant to atherosclerosis.


[Action on human fibrinogen of anti-sera against fibrinogen dissociated chains (author's transl)]. The preparation of immune anti-sera against A alpha, B beta and gamma chains of human fibrinogen is described. Using these anti-sera, the authors have shown that the antigenic parts of the gamma chain are masked inside the molecule of fibrinogen and are not accessible on the surface of the molecule.


[Urokinase. Biochemical therapeutical and therapeutical data (author's transl)]. Two thrombolytic agents are mainly used in patients: streptokinase (SK) and urokinase (UK). UK from human origin is an endopeptidase which is able to convert plasminogen into plasmin. UK is only secreted by the kidney and is only found in urine which is presently the only source of extraction. Studies in man have shown that UK produces a highly reproducible state of enhanced plasma thrombolytic activity with a high fibrinolysis/fibrnogenolysis ratio and a lack of toxicity and antigenicity. The half life in Animal is short as well as the duration of fibrinolytic activity in Man. In clinical experience, positive results have been reported in pulminary embolism while the issues in myocardial infarction are controversial. Suggestive results have been registered in deep vein thrombosis, in ophthalmologic field and in desobstruction of arterio-venious shunts. No evident benefit has been noted in cerebral vascular disease. Up to now, UK has been very well tolerated.


[Study of the foeto-maternal immunization using the LDA test (author's translation)]. In this work, sera of primiparous and multiparous women are studied by the aid of a LDA test and the results are compared to those obtained by the classical technique of complement dependent lymphocytotoxicity. Specificities, that complement dependent lymphocytotoxicity is unable to prove, are checked by the LDA test. Its higher senstivity is confirmed without contradicting the complement dependent lymphocytotoxicity conclusions.


[Improved methods for the cytochemical demonstration of platelet peroxidase (author's transl)]. The variability of results to demonstrate the peroxidase of platelets has been attributed to an inhibition of the enzyme by glutaraldehyde. In order to eliminate this difficulty, two new methods have been employed prior to incubation in the diaminobenzidine medium: 1. Fixation was omitted. 2. Fixation was performed in a mixture of tannic acid-formaldehyde glutaraldehyde. With these two procedures, intense and reproducible peroxidase staining of human platelets and chicken thrombocytes was obtained. Only when the fixation procedure was omitted could the peroxidase of rat platelets be demonstrated histochemically. The importance of the detection the peroxidase as a marker enzyme of the megakaryocyte cell line and the relationships of this peroxidase with those of leukocyte peroxidases are discussed.


[Radioiodine studies with 1231].

[Radioiodine studies with 1231]. The use of 123I (half-life of 13,3 h, no beta emission) results in a marked diminution of thyroid and total body exposure in comparison to 131I. 99mTc-pertechnetate would give the lowest radiation dose, but is not an ideal thyroid agent because it only reflects the iodine trapping mechanism. Several studies show discrepancies between pertechnetate and iodine scans, i.e. Usher and Arzoumanian (2), Turner and Spencer (3). 123I is cyclotron produced, in Switzerland by the 127I (p, 5n) leads to 123Xe leads to 123I reaction. The short half-life needs a modification of the usual testing with 131I. In the present study, thyroid uptakes after 6 h and 24 h, blood sampling after 24 h for 123PBJ and scanning after 6 h give the best results for a complete 123I tracer study of the thyroid. If only morphology of the thyroid is needed, a 6 h scan is done. The normal ranges for uptake values and the 123PBJ are similar to those with 131I. The scans with 123I are definitely faster and of better quality, either by scanner or by camera. The administered doses are 100 muCi for scanning and 300 muCi 123I orally for a complete tracer study. 100 muCi 123I result in a thyroid radiation dose of about 1,5 rads and a total body dose of about 3 mrads [James, Wagner, Cook (1)].


Colitic arthropathies.

Colitic arthropathies. "Colitic arthropathy" is commonly used to describe the arthritis associated with ulcerative colitis or regional enteritis. The term also describes the acute sterile arthritis which infrequently follows infection of the intestinal tract with Salmonella, Shigella, or Yersinia. Sterile arthritis is the most common extraintestinal manifestation of Whipple's disease, in which an unidentified bacteria is present in greatest concentration in the small bowel. Although arthritis and intestinal symptoms are common in Behcet's syndrome, the arthritis is not usually thought of as a colitic arthropathy because of the prominence of other signs, such as oral and genital ulceration and eye involvement. Joint and intestinal manifestations may, however, appear first or overshadow for a time involvement of other systems. Arthritis and arthralgia also occur frequently after jejunocolic and jejunoileal bypass.


A systems approach to the development and evaluation of a minicourse for nurses. An autotutorial, audiovisual minicourse was designed to: 1) inform nurses and other hospital personnel to handle effectively problems associated with contamination and decontamination of respiratory therapy equipment according to the best procedures currently availabel, 2) investigate how different instructional methods are related to student achievement, and 3) determine an effective approach for implementing this educational modality. The subjects-137 allied health students, predominantly nurses, enrolled in introductory microbiology in the Department of Biology, Georgia State University, Atlanta, during the Spring Quarter 1974-were randomly placed in four treatment groups: 1-programmed instruction (PI), 2-audiovisual (AV), 3-AV-PI combined, 4-no exposure to the mini-course-control group. Achievement was measured by comparing pre- and posttest scores on a subject matter achievement test. An analysis of variance revealed that not all treatment population means were equal. Tukey's Honestly Significant Difference Test showed that all three groups exposed to one or both methods of the minicourse scored higher than the control group, with the AV-PI group scoring highest.


An appraisal of symptom relief after coronary bypass grafting. Subjective symptomatic improvement is experienced by 90% of patients after coronary bypass surgery. Objective exercise testing reduces this incidence to 70%. An analysis of the multifactorial genesis of pain relief based on data of non-randomized trials reveals that graft patency plays a dominant but not unique role in causing improved symptomatology. In a number of cases, intra-operative myocardial infarctions seem to explain the pain relief but may also have opposite effects. Changes in left ventricular function operate bidirectionally but data on this variable in relation to changes in symptomatology are not amenable for detailed  analysis. Progression in native vessel lesions apparently opposes pain relief and has its greatest impact in connection with graft closure. Residual post-operative angina is evidently related also to incomplete revascularization.


Transient inhibition of initiation of S-phase associated with dimethyl sulfoxide induction of murine erythroleukemia cells to erythroid differentiation. The murine erythroleukemia cell (MELC) line in suspension culture can be induced to differentiate to erythroid cells by various compounds, including dimethyl sulfoxide (Me2SO). Analysis of the cell cycle, during differentiation induced by Me2SO, using thymidine incorporation, thymidine labeling index, and relative DNA content per cell as measured by flow microfluorometry, demonstrates a transient inhibition of entry of cells into S-phase of the cell cycle which is detected as early as 5 hr and is maximal about 20 hr after beginning of nonsynchronous cultures. Furthermore, in the presence of Me2SO there is restricted binding of the intercalating dye propidium iodide to chromatin from MELC in G1 phase of the cell cycle, as early as 10 hr of culture. This restricted binding of propidium iodide to chromatin is observed in MELC cultured with other inducing agents, such as butyric acid and dimethyl-acetamide, but is not detected with an Me2SO-resistant cell line cultured with Me2SO.


Structure and properties of a hybrid tryptophan synthetase of alpha chain produced by genetic exchange between Escherichia coli and Salmonella typhimurium. Genetic exchange between the structural genes for the alpha chain of tryptophan synthetase [tryptophan synthase; L-serine hydro-lyase (adding indoleglycerol-phosphate), EC 4.2.1.20] of E. coli and S. typhimurium yielded recombinant genes that specified functional hybrid polypeptides. The alpha chains produced by three recombinants appeared to be identical but differed from those of E. coli and S. typhimurium by at least 27 and 8 amino acid residues, respectively. In vivo and in vitro tests of enzyme function suggest that the hybrid alpha chains are near-equivalent to their fully active parental proteins.


[The treatment of chronic pain symptoms with psychotropic drugs (author's transl)]. The results of longlasting experience in the treatment of severe chronic pain are reported. 82% of 103 in-patients with chronic pain responded to a combined treatment with neuroleptic and antidepressant drugs. A dosing strategy for the combbination of clomipramine and haloperidol is described.


Gastric mucosal polyps in pernicious anaemia. In a 4-year follow-up study of 68 patients with pernicious anaemia gastric polyps were observed in 25 patients. In some patients the polyps seemed to vanish completely from one year to another, while they might ascen or increase in  other patients. None of these polyps underwent malignanttransformation during thperiod f observation, and by histological examination they could be classified as non-neoplastic regenerative benign polyps in an atrophic gastric mucosa. In our opinion the surgical attitude to these nonneoplastic gastric polyps in pernicious anaemia should be restrictive.


Affinity chromatography of beta2-microglobulin from human lymphocytes on concanavalin-A-sepharose. Determination of carbohydrate-containing protein molecules complexed with beta2-microglobulin. Beta2-microglobulin was extracted from human lymphocytes with nonionic detergent and separated by affinity chromatography on concanavalin-A-Sepharose. The retarded part of beta2-microglobulin is assumed to be associated with HLA antigens. Using a radioimmunoassay for beta2-microglobulin, the average number of presumably free beta2-microglobulin molecules and of presumably HLA-associated beta2-microglobulin molecules per lymphocyte was estimated to be 3.8 x 10(5) and 1.4 x 10(5), respectively.


Identification of resting human T and B lymphocytes by acid alpha-naphthyl acetate esterase staining combined with rosette formation with Staphylococcus aureus strain Cowan 1. We describe a method enabling the identification of both lymphocyte class and morphology from a single microscopic slide. As a marker for B cells we used surface immunoglobulin. The surface-Ig-carrying cells were rosetted after poly-valent anti-Ig treatment with Staphylococcus aureus strain Cowan 1 (StaCw) and the cells were cytocentrifuged onto a microscope slide. The lymphocytes forming rosettes with StaCw were identical with cells expressing surface Ig studied by fluorescein-isothiocyanate-conjugated anti-Ig. As a marker for T cells we used the acid alpha-naphthyl acetate esterase (ANAE) histochemical marker. The cell smears were first stained for ANAE and subsequently counterstained to distinguish also cell morphology. The ANAE-marker-carrying cells were all included in the population of lymphocytes forming rosettes with sheep erythrocytes. Thus both T and B lymphocytes could be simultaneously identified from a single microscopic slide, and we therefore recommend the method for routine clinical work.


Carrier-specific B cells play a role in the production of an antigen-specific T-cell-replacing factor. An in vitro anti-hapten response to dinitrophenylated monomeric flagellin (DNP-MON) was used to examine the ability of T cells to collaborate with B cells across a cell-impermeable Millipore membrane. It was found that T cells alone were not able to collaborate with B cells across the membrane. However, B and T cells together produced a T-cell-replacing factor that passed through the membrane and partially restored the antibody response of B cells cultured beneath the membrane. Production of the factor was abolished when carrier-specific B cells were inactivated by [125I]polymeric flagellin (POL) suicide. The T-cell-replacing factor was shown to be nondialysable and antigen-specific. It was also demonstrated that macrophages were required for production of the specific T-cell-replacing factor but that the action of the factor on B cells macrophage-independent.


A simple stained protein assay (SPA) for rapid total protein determination applied to spinal fluids. A rapid, simple technique measures small amounts of total protein applied on an agarose gel slab. Alternating current through the gel may reduce diffusion of the protein, which is chemically fixed. The intensity of the Coomassie-Blue-stained spots is a function of the amount of protein determined by comparison with simultaneously run standards. Densitometric and visual estimates of protein in spinal fluids by the stained protein assay correlated with Lowry values highly significantly (n = 28; P less than 0.001, Spearman test of rank correlation). As little as 0.2 mug protein was measured; this figure should be compared with 10 mug for the Lowry method. The reproducibility of the method was +/- 5%.


[Meningeal carcinomatosis: clinical and anatomical study of a case of suprarenal neuroblastoma (author's transl)]. A case of meningeal carcinomatosis associated with cerebral metastases from an adrenal neuroblastoma is described. The clinical picture was ushered-in by bilateral sciatic pain in a 50 years old female and was followed by rapidly progressive sensory-motor deficits of the arms and legs, leading to flaccid quadriplegia associated with paralysis of cranial nerves and episodes of mental confusion. Death occurred 4 months alter, in cardiac failure. At autopsy, a bilateral tumor of the adrenal glands was found. No metastases were detected anywhere except in the central nervous system. Histology identified the tumor as a neuroblastoma; meningeal carcinomatosis, radicular infiltration by tumor cells and parenchimal metastases were found in the central nervous system. Neuroblastoma is typically a tumor of childhood, only 13% of them being found in adult's according to Russell and Rubinstein. Meningeal metastases from adrenal neuroblastoma have not hitherto been reported in the literature. In our opinion, the most likely mode of spread of tumor cells to the central nervous system was hematogenous because of the presence of small multiple intraparenchimal metastases; however, possible spread through the perineural lymphatics, as proposed by others, cannot be excluded, due to the prominent localization of tumor cells at spinal roots level. The main differential diagnostic problems (paraneoplastic neuropathy (Wyburn-Mason) and infectious subacute or chronic meningitis) are discussed. The authors stress the emportance of complete cerebro-spinal fluid examination including a careful search for tumor cells.


The effects of mouse alpha-fetoprotein on T-cell-dependent and T-cell-independent immune responses in vitro. Mouse alpha-fetoprotein (AFP) suppressed the specific antibody response to the T-cell-dependent antigen sheep erythrocytes (SRBC) and the phytohemagglutinin- and concanavalin-A-stimulated DNA synthesis of purified T lymphocytes but failed to inhibit the T-cell-independent antibody response to dinitrophenyl-substituted Ficoll (DNP-Ficoll) and the lipopolysaccharide-stimulated polyclonal B-cell antibody synthesis. Mouse amniotic fluid (MAF) suppressed antibody responses to both T-cell-dependent and T-cell-independent antigens; however, the effects could be differentiated since dialysis of the MAF removed most of the suppressive effect on the DNP-Ficoll response but did not diminish the inhibitory action on the anti-SRBC response. The results indicate that AFP suppresses certain T-lymphocyte functions in vitro and does not act by directly inhibiting B-cell functions.


[Drug interactions in cardiovascular therapy]. Cardiovascular therapy frequently requires simultaneous administration of several drugs. These drugs may interact pharmacokinetically or pharmacodynamically, and most drug interactions are therapeutically useful. The clinical importance of adverse drug interactions is often overestimated; they are almost always predictable and preventable, if their mechanisms are understood and the drug dosages appropriately modified. Coumarin anticoagulants and cardiac glycosides are involved in the most serious interactions. Diuretics, antiarrhythmic drugs, sympatholytics, sympathomimetics and monoamine oxidase blockers also interact in clinically significant fashion with other drugs.


[Cerebrospinal fluid protein electrophoresis in non-inflammatory central nervous system diseases]. Cerebrospinal fluids (CSF) (N = 365) from patients with non-inflammatory diseases of the central nervous system were analyzed for protein distribution by agar gel microelectrophoresis. After subdivision into diagnostically well defined groups, these patients were compared with 79 normal controls. Most of the diseases investigated were found to follow the "plasma-type" pattern. In some of them the deviations from normal were so extensive that a CSF-protein pattern similar to the "acute-phase reaction" in the serum occurred. Moreover, the following characteristics were found: a considerable increase in total protein and the gamma-globulin fractions in neurinomas; a reproducible increase in the alpha1-globulins in metastases of the central nervous system; and a statistically significant difference of CSF protein findings between male and female patients with protrusion of lumbar intervertebral discs.


[Neurological manifestations of Whipple's disease]. Three consecutive cases of Whipple's disease observed by us in recent years have involved neurologic symptoms, i.e. psychoorganic syndromes, gaze palsy, nystagmus, masseteric and pharyngeal myoclonus or papilledema. In one case mononuclear cells in the cerebrospinal fluid, most probably of ependymal origin, were loaded with periodic-acid-Schiff (PAS) positive granules. On treatment with antibiotics the neurologic signs cleared considerably or completely. The findings suggest (a) that neurologic involvement Whipple's disease may not be so uncommon as appears from the literature, (b) that examination of the spinal fluid with PAS staining may be helpful in the diagnosis of such cases, and (c) that neurologic involvement in Whipple's disease may also be amenable to treatment with antibiotics.


Albumin phylogeny for clawed frogs (Xenopus). Comparisons of albumin indicate that the frogs commonly used by North American molecular and developmental biologists under the name of Xenopus muelleri belong to another species, X. borealis. Phylogenetic analysis of the albumin data reveals two major groups of Xenopus species, one containing only X. tropicalis and the other, called the X. laevis grou, containing the remaining species of the genus. The phylogenetic tree, in conjunction with evidence from chromosomes and DNA content, leads to the hypothesis that total genome duplication occurred in the common ancestor of the X. laevis group.


[Significance of the AgHB and of the immune reaction in chronic hepatitis]. The authors studied 496 patients with chronic persistent or aggressive hepatitis, and active or non-active hepatic cirrhosis, and 396 non-hepatic patients. AgHB was detected in the serum by immuno-electrophoresis and by immuno-diffusion and, in the liver, by needle biopsy, using immuno-fluorescence. The liver diagnosis was made histologically. AgHB was found in 34.2% of patients, more often in chronic active hepatitis (53.7%) than in inactive forms (23.2%). This finding may be interpreted as a sign of severity, chronic aggressive hepatitis is more frequently caused by B virus and by its persistence in the liver. In all cases of chronic, aggressive hepatitis studied with AgHB in the serum, AgHB was detected in the nuclei of the liver parenchyma cells. It should be emphasized that there is no significant difference from the immunological point of view, between patients with AgHB and the others, the levels of gamma-globulin and immunoglobulin were higher in the former. The increased frequency of AgHB in the active forms of the disease compared with stabilised forms, reinforces its physiopathological, diagnostic and prognostic significance.


Hemagglutination test for alpha fetoprotein in the diagnosis of primary liver carcinoma. By means of the treatment of the globulin obtained from the monophasic anti-alphaFP serum with pepsin, it has been found to be able to sensitize tannic acid-treated human red blood cells. The sensitivity of the HA test, either on purified alphaFP or with sera from patients with primary liver carcinoma, was found to be favourable as compared with the serological methods commonly employed, such as double diffusion, countercurrent electrophoresis, and complement fixation tests. From a preliminary clinical application on 566 routine specimens obtained from various local hospitals, somewhat greater sensitivity of the HA test was confirmed. Blood specimens from persons known to be free from primary liver carcinoma, namely, 408 from blood donors, 32 from pregnant women, 19 from malignant tumours other than primary liver carcinoma and 5 from benign tumours patients, were all negative except 15 sera from pregnant women. It is well known that the serum alphaFP level of pregnant women is definitely higher than that of normal adults. The specificity of the test has thus been considered established. As the HA test can be carried out with a drop of blood and completed in 30 minutes with simple implements, it is suggested that the method should be suitable for screening test in mass survey in the village and countryside.


Cobalt-57-bleomycin scanning of hila and mediastinum in patients with bronchial carcinoma: a prospective study. Because the results with cobalt-57-bleomycin (57Co-bleo) as a tumour-seeking agent in patients with pulmonary tumours were promising, a prospective study was carried out to test the sensitivity and selectivity of this technique for metastases in lung hila and mediastinum in a group of patients with bronchial cancer. The sensitivity of 57Co-bleo scintigraphy appeared to be higher than that of routine radiological investigations and mediastinoscopy. For this reason it is suggested that 57Co-bleo scintigraphy can be used as a method to select patients for mediastinoscopy.


LD typing and the lack of involvement of SD antigens in the priming process. Peripheral blood lymphocytes with known HLA-SD were typed for LD determinants using a panel of primed cells prepared from SD identical lymphocytes. Then these lymphocytes (with known SD and LD) were primed by x-irradiated cells from the same SD and LD group and their secondary reactions were evaluated. Disparity in SD antigens of responder and stimulator cells did not produce primed cells and lymphocytes were primed only for LD differences. This finding allows LD typing using primed cells from a panel of randomly selected lymphocytes regardless of their HLA-SD.


Normal human sera cytotoxic to cells of human acute leukemia. Eight human sera from healthy individuals with no history of immunization with human transplantation antigens have demonstrated complement dependent cytotoxicity to cells of some patients with active acute leukemia. The antigen(s) detected by these sera are absent from normal and remission lymphocytes and appear most often in ALL patients with a high peripheral lymphoblast count. Some B and T lymphoblastoid cell lines carry the antigen(s) as evidenced by their ability to react with and absorb the antileukemia activity. The data support the existence of at least two overlapping specificities detected by these antileukemia sera. The leukemia antigen(s) show no strong correlation with any known HLA antigen. These observations provide evidence for a human leukemia blast associated antigen or set of antigens which may be immunogenic in man. Their relationship to normal HLA antigens of loci other than A, B or C is unknown.


Cell mediated lympholysis in man: an attempt to type with cytotoxic lymphocytes. From approximately 3,000 CML combinations, originally established in order to evaluate the qualitative and quantitative influence of the serologically defined HLA-A, B, and C antigens on cellular, complement independent cytolysis, 12 combinations were selected yielding reproducible positive cytolysis on allogenic target cells, although no HLA-antigenic sharing could be demonstrated between stimulator and target lymphocytes. These 12 CytoToxic Lymphocytes (CTL's) have been tested in parallell as "CML typing combinations" against lymphocytes from a random population sample of 100 unrelated Danes. Based on a pairwise analysis 11 of these CTL's could be classified into two groups of significantly correlated CTL's. These two groups do not define monospecific traits of allelic genetic origin as judged by a mutually positive correlation and a poor fit to Hardy-Weinberg equilibrium. The traits defined by these groups may be either partially identical or governed by closely linked loci. The same groups were identified and the same conclusions reached after exclusion of those individuals in the population sample where HLA-A, B, C, or D antigens may be targets for destruction. Thus, this study gives direct evidence that known HLA antigens are not sole target determinants in CML or that cytotoxic lymphocytes recognize HLA molecules in a different way than lymphocytotoxic antibodies. The studies underline the immunogenetic complexity of CML although this reaction is most probably governed by genes in the HLA region. It is suggested that cytotoxic lymphocytes may recognize "backbone structures" of the HLA molecules.


HLA restriction of non-HLA--A, --B, --C and --D cell mediated lympholysis (CML). The aim of our study was to define target determinants other than those coded for by the classical HLA-A, -B, -C or -D loci which were responsible for killing in CML. In one of the families studied, strong evidence was found for the existence of a determinant coded for within the HLA region. CML was restricted to targets carrying the classical HLA-Bw35 and Cw4 determinants but the targets were neither HLA-Bw35 nor Cw4 themselves. We therefore concluded that this new HLA determinant was either the product of a new locus closely associated with HLA-B or that it was a product of the classical HLA-B locus which has not been recognized by serology.


Joint report of the B lymphocyte specificities workshop of the France-one region. The analysis of 182 selected anti-B cell sera on 102 cells allowed us to identifysseveral clusters of sera. They showed no correlation with HLA-A, B or C specificities but many associations with the HLA-D determinants. In 10 families, most of these sera segregated with HLA, and five recombinants showed a linkage with the BD or D end part of the MHC. The panel distribution and the family analysis indicated that at least one (the Ly-Li system) and probably two segregant series could exist close to the HLA-D locus.


Absorption and elution of anti-DLA-A and B antibodies with acetone-dried dog spleen powder. Acetone-dried powders were prepared from the spleens of DLA-serotyped dogs and assayed for their specific absorptive properties for anti-DLA-A and B antisera. The specific activity of two different antisera (anti-DLA-A9 and anti-DLA-B13) was readily absorbed with acetone-dried powders prepared from the spleens of dogs of the corresponding DLA types. This specific activity was recovered by the elution of the powder used for the serum absorption. The same method was used to narrow the specificity of a highly polyspecific antiserum. The comparison of the absorption properties of acetone-dried spleen powder versus fresh spleen cells shows that the treatment with acetone does not modify qualitatively and quantitatively the DLA specificities.


Cellular presensitization to alloantigens in haemodialyzed patients. The state of cellular alloimmunity in haemodialyzed patients has been assessed by a microcytotoxicity assay and compared with that in healthy donors. Some of the patients were also studied during the weeks following a first kidney transplant rejection. For comparison, lymphocytes of multiparous women have been studied. Skin fibroblasts from a panel of normal donors were used as targets, and effector cells were cryopreserved peripheral blood lymphocytes. Lymphocyte-mediated cytotoxicity (LMC) demonstrated restricted reactivity against target cells, an indication of specificity. It detected presensitization more often than a standard test for cytotoxic antibodies. This difference is not attributable to differences in sensitivity of the two tests, since some patients were at least once LMC negative and cytotoxic antibody positive, and the antigens detected by both tests were different in patients who had positive LMC and cytotoxic antibodies simultaneously. In some experiments, LMC target determinants were not HLA serologically detectable antigens. Furthermore, lymphocytes obtained after transplant rejection were cytotoxic for targets which did not share the donors' serological mismatches. These results suggest that antigens other than HLA-A and B may be the determinants recognized in the microcytotoxicity assay.


Immunogenicity of HLA antigens purified from serum. The immunogenic properties of HLA-A9 antigens isolated from serum have been evaluated. A9 antigens at various stages of purification can elicit the formation of cytotoxic antibodies which become operationally specific to A9 either after absorption of the xenoantisera with cultured human lymphoid cells or human red blood cells, or after dilution of xenoantisera with human serum. A9 xenoantisera do no affect mixed lymphocyte reactions between allogeneic lymphocytes carrying A9, suggesting that coating of antigens of the A locus does not impair the functional activity of lymphocytes in the mixed lymphocyte reaction.


The effect of timing of skin grafts on subsequent survival in ALS-treated, marrow-infused mice. It has previously been shown that the survival of C3H/He skin grafts can be prolonged on ALS-treated (C57 x A)F1 mice by the injection of C3H/He bone marrow cells 7 days after grafting. Experiments have now been done to study the influence of timing of the skin graft on its subsequent survival. Single grafts were placed either before or after marrow was given. Paired grafts on the same animal were also studied, one placed before and one after marrow was given. Grafts placed before marrow was given, whether single or paired, showed equal and significant prolongation while grafts placed after marrow was given showed only slight prolongation compared with ALS controls. Paired grafts showed distinctly different survival curves depending on their time of placement in relation to injection of marrow. The pattern of graft survival suggests that the graft prolongation achieved is attributable to a mechanism similar to enhancement. Experiments were also done to see whether a state of preexisting immunity to the skin graft donor induced by the injection of marrow could be manipulated to achieve prolonged graft survival. (C57 x A)F1 mice were treated with ALS, given injections of C3H/He marrow, and grafted 56 days later with C3H/He skin either with or without additional ALS at the time of grafting. If no ALS was given grafts were rejected in accelerated fashion, indicating that the previous injection of marrow had sensitized the recipient. With additional ALS, the prolongation of graft survival achieved far exceeded that seen using our standard protocol of skin grafting a week before marrow is given. This represents one of the first demonstrations of positive alteration of a preexisting state of immunity to achieve graft prolongation which exceeds that expected by giving ALS immunosuppression alone to a presensitized animal.


[Immunologic properties of fructose diphosphate aldolase in rabbit muscle under normal conditions and during fasting]. Methods of double diffusion failed to detect differences in immunological properties of aldolase from muscles of normal rabbits and those fasting for a long time. Therefore a quantitative method was used to inhibit the aldolase activity by homologous and heterologous antisera. The data obtained evidence for appearance of additional antigen determinants in an algolase molecule of the animals fasting for a long time; the determinants being sterically connected with the site of the enzyme active centre.


Adriamycin plus bleomycin versus cyclophosphamide plus vincristine in advanced carcinoma of the uterine cervix. The paper reports the results of a prospective controlled study with two drug combinations (adriamycin plus bleomycin versus cyclophosphamide plus vincristine) in 34 consecutive patients with advanced or recurrent carcinoma of uterine cervix. Despite adequate dosage, the incidence of complete and partial remission was low (10% vs 20%) and not superior to that usually obtained with single agent chemotherapy. By adding objective improvement, the over all response rate was 47% and 26%, respectively. The duration of complete plus partial remission was 7.5 and 7.2 months, the median survival for responders 19 and 8.3 months, respectively. After cross over, adriamycin plus bleomycin yielded response in 4/10 patients, cyclophosphamide plus vincristine objective improvement in 1/3 patients. Since the control of advanced cervical carcinoma remains difficult, a combined modality approach with radiotherapy plus adjuvant chemotherapy for stages IIB and III appears worth of trial.


The migrating thermodynamic quantum hypothesis for cytoplasmic streaming, sodium pumping and other cell biological phenomena, deduced from biofunctional considerations of the ultrastructure of brush border microvilli. An attempt is made to reconcile experimental data dealing with, inter alia, cytoplasmic streaming in Characean algae, contraction in actomyosin systems. Na+- and -K+-simtulated ATPase activity and the ultrastructure of brush border microvilli. It is postulated that myosin molecules transfer energy from ATP to an actin-containing filament and that a high energy conformation is subsequently propagated along the filament. At regularly spaced intervals corresponding to the length of an actin-tropomyosin subunit, the propagation of high energy involves rejection of a pressure pulse in the direction of cytoplasmic streaming. Proteins in solution capable of storing the thermodynamic energy represented by the pressure pulse will either migrate in the opposite direction or conserve the quantized cytoplasmic flow generated by the actin-containing filaments. At sites where actin filaments are attached to the plasma membrane the high energy is propagated in another direction leading to expulsion of sodium ions and neutralization of the vectorial pressure pulse.


Therapy of advanced esophageal cancer with bleomycin, irradiation and combination of bleomycin with irradiation. Results from treating 51 patients with advanced esophageal cancer are presented. Fifteen patients were treated with Bleomycin, 12 with radiotherapy, and 24 with a combination of bleomycin and radiotherapy. The best results were achieved in the group of patients treated with combined therapy showing 62% objective remissions (15/24) which was statistically significant (P less than 0.001) in comparison to the other groups. In the Bleomycin therapy group, there were 26% objective remissions (4/15), and in the group treated only with radiotherapy 33% (4/12)- The median duration of remission was 9 months in the combined therapy group, 6.3 months in the group treated with radiotherapy, and 2.6 months in the Bleomycin treated group. The authors concluded that the combination of Bleomycin and radiotherapy seems to be a further step in palliative treatment of advanced esophageal cancer.


[Bacterial infection in cows associated with abortion, endometritis and sterility]. Isolated were two types of bacteria (having common morphologic and cultural behaviour and related antigenic composition) from aborted fetuses and placentae of cows with a positive reaction after both Huddleson and placentae of cows with a positive reaction afterboth Huddleson and Wright. They were shown to be new species of the group Mimeae and the genus Yersinia. It was demonstrated through immunodiffusion and immunoelectrophoresis that these new bacteria present antigenic relationship with Brucella organisms. A common O-antigen determinant was found to exist in the isolated bacteria and the S-and R-Brucellae and Br. ovis. The pathogenic effect was tested of the newly isolated bacteria on experimental animals, establishing a certain degree of uterotropism. An abortion was reproduced in a pregnant heifer by means of the intravenous injection of a bacterial culture. The serologic reaction presented by the animal proved comparable with that of cows exhibiting a natural infection process.


[Effect of lactoplasmin, gamma-globulin, Filatov's swine embryo tissue preparation and hyperimmune rabbit serum on several hematologic indices and morbidity among cattle with bronchopneumonia]. Studied was the effect of lactoplasmin, gamma-globulin, a tissue preparation of swine embryos after Filatov, and a hyperimmune rabbit serum on the hemopoieis, the white blood picture, and the morbidity rate in calves with bronchopneumonia. It was found that these preparations influence favourably the white blood picture, the clotting time of blood, and the resistance of calves. With the test calves the morbidity rate was lower than in the controls. Best prophylactic effect was produced with use of tissue preparations and lactoplasmin.


[Effect of Filatov's tissue preparation and and a globulin preparation on weight gain in calves]. A comparitive experiment was carried out with 81 calves, aged 4-15 days, to establish the effect of a tissue preparation of swine embryos after Filatov, colostral lactoplasmin, and bovine gammaglobulin as prophylactic and therapeutic means, on the sera proteins. It was found that these preparations show no influence on the protein fraction ratio. It has also been pointed out that these agents produce a strong stimulative effect on the average daily weight gain of calves up to the sixtieth day following treatment.


[Relationship between the viability and pathogenicity of Heterskis gallinarum and the intensity of invasion and age of the infested chickens]. It has been found that the survival rate of Heterakis worms in chickens aged from one to seven months is directly dependent on the number of Heterakis eggs that have gained access in them only in the case of lower numbers of infective eggs (10 and 50). At comparatively larger numbers of eggs (500 and 2500) the survival rate has been highest at the 3- and 4-month-old chickens, and the morphologic changes in this age group are most pronouncedly expressed. Investigations have shown that the greatest survival rate corresponds to the weakest increase in the leukocyte count and the amount of the gamma-globulins in the 3- and 4-month-old chickens. In the one- and 2-month-old ones the Heterakis infection has caused a strong increase in the leukocyte count, and in those aged 5-7 month-old there has been also an increase in the gamma-globulins. The biochemical indices and the morphologic changes have not in all cases been directly dependent on the age of the infected birds, the number of the infective eggs given, and the number of the Heterakis helminths that have survived. Heterakis injection caused by a greater number of eggs is present by worms of a smaller size. Chickens infected at the age of more than five months have worms among which the female samples are considerably more than the male ones as compared with the respective numbers found in one- to 4-month-old birds.


Vascular lesions following perfusion with bleomycin. Electron-microscopic observations. During intra-arterial perfusion therapy of oral squamous cell carcinomas with bleomycin, circumscribed necrotic areas in the perfused region are observed in a few cases. These are usually located in the acral regions. As the cause, a lesion of the blood vessels with formation of microthrombosis could be demonstrated. Electron-microscopic observations of the blood vessels in five bleomycin-perfused tumor areas demonstrated lesions of the endothelium characterized by swelling of the cells, formation of intracytoplasmatic vacuoles and villous projections into the lumen of the vessel. In arterioles, separation of the endothelium from the underlying tissue, swollen smooth muscle cells and destruction of elastic lamellae were found. These were the pacemakers for the formation of thrombosis. A negative influence of the vascular lesions on the cytostatic effect on the tumor is likely. Vascular lesions also constitute one of the initial factors for the development of the bleomycin-induced lung lesion (bleomycin lung).


[The results of palliative radiotherapy in 50 unselected cases of bone metastases]. A report is given on the results achieved in the palliative treatment of bone metastases by means of conventional radiotherapy in fifty unselected patients with different types of primary tumours. 14 % showed and excellent response and in 56 % a good result was obtained. In 14 % of the patients the treatment was unsuccessful, while in 16 % it was not possible to complete therapy because of the poor general condition of the patients. The response was independent of the histology or localization of the primary tumour.


[Ventricular arrhythmias in coronary heart disease. Analysis by long-term-ecg, coronary arteriography and left ventriculography (author's transl)]. A dual channel long-term-Ecg monitoring system was used to investigate arrhythmias in 90 patients undergoing diagnostic coronary arteriography. There was no significant difference of ventricular arrhythmias during an observation period of 10 hours before and after cardiac catheterization. The incidence of ventricular premature beats (VPB) was significantly higher in coronary patients than in normal controls (normal coronary arteries and normal ventriculograms) or in a group of 24 healthy soldiers. In patients with coronary artery disease (CAD) the incidence of VPB's was 82 %. There was, however, no significant correlation between the severity of CAD and the number of VPB's although patients with 3-vessel disease showed a tendency to produce more extopic beats. In contrast, patients with generalized or regional left ventricular akinesis (systolic shortening less than 15 %) showed a significantly higher number of VPB's than patients with normal or hypokinetic ventricles. In addition the analysis of qualitative criteria of ventricular arrhythmias with regard to their prognostic significance following Lown's definition showed the same close correlation with ventricular dysfunction. In the group of patients with VPB's of high incidence and prognostic importance cardiac index and ejection fraction was significantly decreased and left ventricular enddiastolic pressure significantly elevated. In conclusion, coronary patients with left ventricular akinesis are prone not only to produce congestive heart failure, but also life-threatening ventricular arrhythmias.


[The ultrastructure of human pituitary adenomas (author's transl)]. 34 pituitary adenomas were examined by light and electron microscopical methods. Slices of tumor tissue fixed in formaldehyde or Bouin's solution, respectively, and embeded in paraffin were stained by hematoxylin-eosin, Goldner's method (including Orang G), periodic acid Schiff (PAS) reaction, and in some cases by Herlant's tetrachrom. The ultrastructure was studied using tumor tissue fixed in glutaraldehyde within 1 hour after removal. The adenomas were classified by their light microscopical characteristics as chromophilic or chromophobe tumors. Employing the PAS reaction and Goldner's staining method, 27 adenomas were found to give intense or weak staining reactions. By electron microscopical investigation , all the adenomas studied were seen to contain secretory granules more or less densely packed within the cytoplasm. The number of these granules was strongly correlated with the intensity of the tinctorial properties of the tumor tissue. Out of 11 acidophilic adenomas, 10 were observed consisting of typical STH cells. 4 acromegalic patients were found to possess heavily or poorly granulated STH cell adenomas (two patients in each of these groups). One patient with a clinical history of liver cirrhosis and gynecomastia was observed bearing an acidophilic (and erythrosinophilic) adenomatous hyperplasia of prolactin cells, 13 tumors consisted of cells exhibiting almost weak amphophilic staining properties and secretory granules of 100-250nm diameter, thus resembling cells which have been reported to produced ACTH. One of the patients suffering from these adenomas, showed the clinical signs of M. Cushing. By ultrastructural criterions, 3 adenomas with PAS-positive tumor cells were considered to be composed of gonadotropic cells. Only 7 adenomas were observed which did not give any chromophilic reaction. These tumors consisted of extreme poorly granulated cells which could not be significantly associated with one of the pituitary hormones by their morphological properties. In respect of the abundance of mitochondria, 4 out of the adenomas were designated as oncocytic tumors.


Evidence for the involvement of the Na+-K+-ATPase in the mechanism of axonal protein and nucleoside transport. [3H]Proline and [3H]uridine were injected into both eyes of the goldfish. 1 h before and after this injection 3X10)-6)M ouabain was administrated unilaterally to the retina. 8 h and 24 h after tracer injection the radioactivity in the retina, optic nerve and tectum was measured. It is suggested that the inhibition of the neuronal Na+-K+-ATPase inside the retina is responsible for the reduction of the labelled material transported into the optic nerve.


Effect of lindane on radio-carbon (14C) incorporation by Rhizobium japonicum. Experiments conducted in vitro with three levels (1, 2, and 5 ppm active ingredient) of the insecticide lindane (gamma-BHC) showed no effect on the growth of Rhizobium japonicum, but altered the incorporation of radio-carbon (14C-glucose) into the different constituents of the growing cells. While all the three levels of the insecticide significantly depressed the incorporation of radiocarbon in the alcohol-extractable fraction, with no effect on the alcohol-ether soluble fraction of the cells, the 2 and 5 ppm levels enhanced the incorporation rate in the cold-TCA soluble fraction, but reduced it in the hot-TCA soluble fraction. Only with the 5ppm level of the insecticide treatment an increase in the specific activity of the insoluble protein fraction of the cells was observed. The results indicated that lindane, at various concentrations, affected the carbon (glucose) metabolism of the Rhizobium cells.


Immunoglobulin diversity: correlation of non-allelic antigenic markers with the basic sequences of the variable region of human lambda chains. Three forms of the amino terminal half (variable region) of human pathological lambda light chains of immunolglobulins were identified antigenically. By study of all completely sequenced Bence Jones proteins hitherto analyzed and a greater number of proteins subjected to automated sequence determination as well as normal light chains three distinct isotypic basic sequences were identified. The basic sequences are shown to be associated with characteristic antigenic markers representing three V region genes encoding the variable half of lambda chains of immunoglobulins.


[Applications of mycoserological diagnostic methods in phytopathology. 2. Relations between the position of precipitation lines and reaction specificity]. Immunsera from rabbits were produced against 8 Fusarium species by way of immunisation using 10 injections with increasing antigen dosis. Homologeous and heterolgeous seroreactions were carried out by using angular double diffusion test. These investigations are aiming at the determination of the relations between the position of the precipatation-lines and the specifity of the reactions. The results are showing, that it is possible to characterize the quality of the antigen by means of the reaction speed of the immunologeous reagents. By this way it is also possible to differentiate several groups of Fusarium species with similar antigen-properties.


[Stress ulcer; origin and treatment (author's transl)]. Conditions like stress and shock influence each other and lead to irritation of the regio hypothalamica not only in its anterior but also in its posterior part with excitement of the n. vagus or the anterior lobe of the hypophysis respectively (ACTH-release with following release of cortisole). Irritation of the n. sympathicus and diminution of the circulating plasma volume are additional sides of the pathophysiological course. Sequels of this are: reduction of blood flow through the gastric mucosa, decrease of the protective ability of the mucus, secretion of an especially aggressive gastric juice and reflux of bile into the stomach. They lead to a breakdown of the mucosa barrier with releasing of histamine in the mucosa, to peptic, destruction of the gastric walls damaged regions and thus to the development of erosions and acute ulcers (AGML=acute gastric mucosal lesions). As to the aspect, these ulcers cannot be differentiated from those lesions of the mucosa which are induced by medicaments. To recognize a complicating hemorrhage in time an emergency endoscopy is recommended. Complicated perforations are seldom observed. Prognosis is bad in patients with complications. Therefore prophylactical measures are of special importance like vagotomy, medicamental blockade of the n. vagus and influencing of the n. sympathicus, infusions in time and in sufficient extent, application of anti-acida and, in case of bile reflux, cholestyramin. Therapy of hemorrhage should be made according to the endoscopical findings. Conservative therapy should be the first aim. If surgical therapy cannot be avoided, methods of minimal risk should be practised.


[Mechanical ileus (author's transl)].

[Mechanical ileus (author's transl)]. 181 patients with mechanical bowel obstruction were treated between 1965 and 1974 at the First Surgical Clinic of the University of Vienna. 172 were operated, 7 had conservative treatment. 1. the mortality was 24,3% and infavorably influenced by a) advanced malignant tumors, b) age over 60 years, c) preexistent peritonitis. -2. Enterotomy for bowel-decompression was in no case followed by a complication.- 3. Nobles operation should be performed only totally and in cases of severe adhaesions. 4. Discussion of the one stage operation in large bowel obstruction, which is only indicated in patients with good general condition. The high letality of 47% after operations in cases with ileus due to carcinosis peritonei requires critical indications for these operations.


[A gradual method for a more physiological hormonal contraception]. The multiple physiologie stages of method by oral hormonal anticonception was reported, which have been in use in combination. Since 1969 about 362 women at the average age of 27,5 years received 10281 cycles, that means in an average cycles from 28,4 days, the stage method from 11/10 days or 7-7-7 days rhythmus.


[Recommendations for the use of cryotherapy in gynecology]. Bases on the experiences with the application of cryotherapy to 393 patients with 440 cryosurgical operations, special and general experiences concerning the cryotherapy in gynaecology are presented. Accordingly, the cryotherapy is suitable to increase the number of the conventional methods of medical attendance to the vulva, the vagina, and to the cervix uteri. The main possibilities of application are those to the sanitation indications of the portio, to the removal of acute condylomes, and to the pallative as well as to the curative therapy of the vulva carcinomes.


Detection of antigenic differences among street and fixed rabies virus strains by the counterimmunoelectrophoresis test. Using the counterimmunoelectrophoresis test, two street rabies virus strains (Mangosta and Apipe) revealed antigens not detected in the standard challenge virus (CVS). No antigenic differences, however, were found between CVS and another fixed rabies virus strain (strain 91) by this method. The results of serum neutralization tests revealed similar antigenic relationships among the rabies virus strains studied. These findings are discussed in terms of their significance to antigenic variations in rabies virus strains.


[Serological analysis of two complex Salmonella respectively Arizona O-groups (Salmonella O:48 and O:64 - Arizona O:5 and O:29) with the object of combining them into one Salmonella O-group 48 within the Kauffmann-White-schema (author's transl)]. In 1963 KAUFFMANN divided O-group Y (= O:48) of the KAUFFMANN-WHITE-Schema into 3 sub-groups, e.g. 481, 482 - S. dahlem; 481, 482, 483 - S. djakarta; 481, 483, 484 = Citrobacter no. 2624/36. He also recommended the use of the two serotypes S. dahlem and S. djakarta for the preparation of a diagnostic group-serum. At that time, serological relations- especially O-antigenic relations (and even some identities) - between the separate Salmonella and Arizona genera were known, viz. between the Salmonella group 0:48 and the Arizona group O:5. It has now been found that there exist also close serological relations between the Salmonella O-groups 48 and 64 on the one hand and to the corresponding Arizona O-groups 5 and 29 on the other hand, in connection with which the special factor 484 defined by KAUFMANN in the Citrobacter culture no. 2624 embraces the whole Salmonella group O:64 (= Arizona group O:29). Therefore, every Salmonella O:64 strain and Arizona O:29 serotype respectively can be agglutinated with factorserum 484, defined by KAUFFMANN. A special O:64 serum is no longer required. The Salmonella antigen 64 (Ar. 29 or 5.29) has a rule the partial antigens 481, 483, 484 (= Ar. 5,29). Only a few serotypes do not possess factor 483; their components are 481 and 484 (= Ar. 29). The evidence of our findings demonstrates that the Salmonella O-group 64 (= Arizona 29) should be combined with O-group 48 (Ar. 5) and erased from the original Kauffmann-White-Schema and the Arizona Antigenic Schema to avoid a wrong diagnosis.


[On the similarity of antigen between fungi and Salmonella. 4. Communication (author's transl)]. The immune sera for Candida membranefaciens (C. majoricensis), Candida guilliermondii var. carpophila, Metschnikowia bicuspidata, Syringospora stellatoidea and Torulopsis candida agglutinated Salmonella cholerae-suis (6,7). The immune serum for S. cholerae-suis agglutinated Candida membranefaciens (C. majoricensis), Candida guilliermondii var. carpophila, Metschnikowia biscuspidata, Syringospora stelladoidea and Torulopsis candida. Absorption and agglutination cross test demonstrated common antigen factors in the tested fungi species and in S. cholerae-suis (6,7).


[Experimental infection of domestic animals with R. prowazeki and R. canada]. The authors infected lambs with R. prowazeki and R. canada to ascertain their possible role in the natural infection of the animals. The lambs were infected subcutaneously with increasing doses; rickettsiemia was recorded with the aid of tests on guinea pigs and Ixodidae and Argasidae ticks fed on the lambs. Dynamics of antibody formation was ascertained in the infected animals in the agglutination reaction and in the complement fixation test. The antigenic affinity of R. canada and rickettsia of the typhoid group and the presence of common antigenic determinants with the Proteus OX19 was confirmed. The absence of any clinical manifestations, the character of antibody formation, impossibility of inducing the generalized infection and of the isolation of the causative agent from the blood pointed to the low susceptibility of lambs to R. prowazeki and R. canada; thus a possibility of circulation of the causative agents of typhius among the domestic animals scarcely probable.


[Avidity criteria in assessing the functional activity of antigens, antibodies and non-specific serum inhibitors on a model of the kinetic reaction of hemagglutination suppression with arboviruses]. The functional activity of some arboviruses of groups A and B, of the antibodies and serum inhibitors was studied on a model of the kinetic hemagglutination inhibition test (HAI) by different avidity criteria (velocity, completeness and stability of formation of a neutral complex). The avidity indices of the antigens, antibodies and the inhibitors proved to depend on the group, species and strain peculiarities of the arboviruses, the method of preparation of the antigen, the biological species of the donor of the immune and normal blood sera, the method of treatment of the sera and a number of other factors. There proved to be no constan-correlation between the avidity of the strain and the avidity of the serum immune to it. Inhibitors of the normal rabbit and human sera were not less effective in comparison with the specific antibodies to a number of viral strains of tick-borne encephalitis and Japanese encephaliti or even exceeded them by the avidity indices to the antigens in the HAI test. The most active (functionally) strains can be recommended for obtaining high-quality viral (antigenic and serum) preparations.


[Heart rhythm disorders in acute cerebral circulatory disorders]. The authors studied 101 patients with a combination of acute disorders of brain circulation and changes in the rhythm of heart activity in the form of sinus tachycardia, extra-systolia, fluttering arythmia. In ischemic strokes fluttering arythmia was encountered quite frequently while as in hemmorhages it was almost never seen. In 20 cases disorders of heart rhythm appeared following several days or more after the stroke. These data permit to assume that disorders of rhythm in the heart activity may be one of the pathogenetical factors of acute disorders of brain circulation. Their appearance after strokes is most frequently associated with signs of acute or exacerbated coronary insufficiency. Flutter arythmia in patients with strokes should be taken into consideration indifferential diagnosis of brain haemmorhages and infarctions.


Effect of antibody on interaction between vitamin B2 and riboflavin apoprotein. 1. Dissociation of riboflavin from flavoprotein and from the flavoprotein-antibody complex occurs under the same conditions. 2. The precipitated apoprotein-antibody complex retains 15% of the apoprotein capacity to bind riboflavin. After solubilization of the complex in 0.3 M-KCl or 1 M-urea, the binding of riboflavin amounts to 80 - 90% of its capacity. 3. The apoprotein modified by oxidation of 50% of tryptophan residues loses the ability to bind riboflavin but its immunological reactivity with the anti-flavoprotein antibody is similar to that of native apoprotein. The apoprotein with all tryptophan residues oxidized shows much lower immunoreactivity. 4. The obtained results suggest that in riboflavin flavoprotein the region around the riboflavin-binding site does not show the properties of an antigenic determinant.


The accumulation of immunoglobulins in the human tonsil. The concentration of 5 types of immunoglobulins in both serum and the faucial tonsil was determined. The level for all types was significantly higher in the tonsil. IgG was detected as the main immunoglobulin in the tonsil, while the concentration of the other types was in about the same range. With the shortening of the biological half-live the accumulation index increases. The results give evidence for the antibody formation in the tonsil.


[Evidence of pseudoisocyanine--positive endocrine cells in the gastric mucosa of the dog]. The tunica mucosa of the stomach and the other parts of the intestine (duodenum, jejunum, ileum colon) of the dog has been investigated in order t to demonstrate insulin producing cells. By means of thepseudoisocyanine-reaction it was possible to visualize in the lamina epithelialis of the stomach singular cells containing metachromatically reacting granules. It was possible to distinguish these cells from mast cells localised outside of the lamina epithelialis of the tunica mucosa. The value of this observation is given by the fact that until now hormone producing cells could be demonstrated in the laimina epithelialis of stomach and intestine of mammalia with exception of insulin-producing cells.


Characterization of human malignant melanoma cell lines. IV. Cytologic and histochemical characteristics. The cytologic and histochemical characteristics of seven established human melanoma cell lines were studied using monolayer culture and cytocentrifuge perparations. The morphology of the cells is different in the two preparations. There is a strong resemblance between the Cytocentrifuge preparations and the histological tissue sections and cytologic smears that are used in routine diagnostic work.


Stain using celestine blue B as substitute nuclear stain in routine cytologic examinations. It was found that an improved Celestine blue B stain could be used satisfactorily for routine staining of cytologic smears as a substitute nuclear stain for hematoxylin. Whatever the clinical material, the results were no different from the findings obtained by staining with the usual Papanicolaou's method using hematoxylin.


In vitro histamine release from leukocytes in penicillin allergies. The definite diagnosis of Type I allergy against penicillin is very important. The in vivo tests used for this purpose may have some disadvantages for the patient. Among the in vitro tests used for the evidence and differential diagnosis of Type I allergy against penicillin, the determination of histamine release from leukocytes and the detection of IgE by the RAST test are the most promising. We have used the test of histamine release from leukocyte in this study of 18 cases, nine of whom had Type I hypersensitivity reactions to penicillin and comprised the study group, the rest were control cases. The per cent of histamine release in the control group was "zero" while in the study group it ranged from 3.9 to 51.7 per cent. The results indicate that the method used in this study is a sensitive and reliable method for the diagnosis of Type I penicillin allergies.


Effect of encephalitogenic protein on migration in agarose of leukocytes from patients with multiple sclerosis. A longitudinal study of patients with relapsing multiple sclerosis or with cerebral infarction. Ten patients with MS were studied with leukocyte migration in agarose technique to detect changes in reactivity to encephalitogenic protein in connexion with a relapse. Six showed significant reactivity within a few days after the relapse. It decreased or disappeared during the 2 weeks after the relapse, but sometimes reappeared and was found in tests performed 2-3 months later. Five patients with cerebral infarction were studied in a similar way--in three, marked reactivity was noted within a few days after the stroke; in these, reactivity decreased or disappeared in later tests. In the two other patients, reactivity appeared in the second and/or third test. The possibility of a reactivity as in epiphenomenon due to CNS tissue destruction is discussed, and the need for antigens with a more restricted specificity for such an analysis is stressed.


Fundamental study of automatic cyto-screening for uterine cancer. I. Feature evaluation for the pattern recognition system. A basic study was carried out to determine the parameters of a pattern recognition system for the automatic assessment of cytologic cell samples. Various cell features were extracted, whose combinations were evaluationed by an "ambiguity function". It was shown that the highest reliability can be obtained with a combination of the features of nuclear staining, nuclear area, area of cytoplasm, nuclear/cytoplasmic ratio, nuclear shape and chromatin pattern. However, recognition of the nuclear edge and chromatin patterns is complicated and makes automation difficult. Even if these two features are omitted, false positives do not exceed 20 per cent. Consequently screening of abnormal cells can be carried out by image recognition procedures by the use of a computer.


Myopathies with abnormal mitochondria. A clinical, histological, and electrophysiological study. Among 135 consecutive patients with myopathy, 17 showed abnormalities in the mitochondria of muscle. In eight of these patients the abnormalities were demonstrated by electron microscopy. In all patients Gömöri trichome stain showed red masses at the sites of the mitochondria and diformazan deposits when stained for mitochondrial enzymes. The patients could be divided into three groups: i) Nine patients had weakness of the extra-ocular muscles, either alone or associated with weakness of skeletal muscles and non-muscular signs. One patient with the oculo-cranio-somatic syndrome had two affected sibs. ii) Four patients had a facioscapulohumeral distribution of weakness. Three (two sisters and a maternal aunt) were in the same family, and the fourth patient had an affected sister. iii) Four patients were clinically heterogeneous. When mitochondrial alterations were the only pathological change in many fibers in a muscle, they were most often associated with an ocular or oculo-cranio-somatic syndrome. Electromyography showed changes indicating or suggestive of myopathy in all but one patient. There was a discrepancy between severe changes in the EMG and nearly normal fibers by hematoxylin and eosin and van Gieson stains. Serum creatine kinase was increased in 10 of 17 patients, in most 2-4 times the upper limit of normal.


Fundamental study of automatic cyto-screening for uterine cancer. II. Segmentation of cells and computer simulation. In images of Papanicolaou stained cells 64 gray levels have been differentiated by scanning densitomery. One of the two peaks in a differential histogram indicates the threshold of the cytoplasm, the other that of the nucleus. The two modes indicate where in the digitized image of good segmentation of the cell from its background and the nucleus from the cytoplasm can be accomplished.


About demyelinating properties of humoral antibodies in experimental allergic encephalomyelitis. In vivo and in vitro studies. In order to elucidate the role of humoral antibodies in the pathogenesis of myelin lesions in experimental allergic encephalomyelitis (EAE) a combined in vivo and in vitro study was done using rabbits immunized with the purified A1 basic protein. Rabbits injected with whole white matter were used for comparison. Demyelinating activity appeared in the rabbit sera 5 days after injection, as tested in myelinated organotypic tissue cultures. In spite of this no lesions of the myelin preceded the appearance of inflammatory cells in the living animals. In the spinal cord changes in vascular permeability, as revealed by leakage of Evans blue-albumin complex, appeared at the same time as the cells. In contrast to in vitro, the mere presence of circulating antibodies in vivo does not appear to be enough to cause structural changes of the myelin. Possible reasons for this discrepancy are discussed; it is emphasized that the inflammatory changes develope first in areas where the so-called blood-brain barrier to diffusion of proteins is lacking.


A quantitative electron microscopic study of the ageing human cerebral cortex. A recent quantitative electron microscopic study of biopsy samples of the cerebral cortex of neurologically normal individuals, aged between 15 and 54 years, has shown that atypical inclusions are present in neuronal and glial processes in small but appreciable numbers (Rees). It would be of interest to know whether these inclusions accumulate with age. This study therefore applied the same quantitative methods used in the previous study, to autopsy samples of frontal and temporal cortex from 3 non-demented ageing human brains (70-76 years). The results showed that in the areas of cortex examined, the number of inclusions in neuronal processes did not increase with age. However, the number of dense deposits in the cell bodies and processes of oligodendrocytes did increase significantly with age. In agreement with previous studies corpora amylacea were found in astrocytic processes. Senile plaques were not observed.


Survival and liquid holding recovery in UV-sensitive strains of Saccharomyces cerevisiae after treatment with chemical mutagens and radiation. Two UV-sensitive mutants of Saccharomyces cerevisiae rad 3 and rad 6 were tested for sensitivity to X-rays, MMS, EMS, HNO2 and DEB. Rad 3 mutant is more sensitive than the wild type strain only to HNO2 and DEB, while rad 6 is cross sensitive both to X-rays and all chemicals tested. Liquid holding recovery (LHR) was studied by comparison of cell survival immediately after mutagen treatment and after 5 days of storage in phosphate buffer. LH greatly increases cell survival of rad 3 mutant after DEB and slightly after EMS, MMS and HNO2, while after UV treatment LH significantly decreases survival of this mutant. LH increases survival of rad 6 mutant after exposure to UV, MMS and HNO2, but decreases survival of DEB-treated cells. Exposure of wild type strain to LH results in an increase of survival after UV, and DEB but not after MMS and HNO2. The results suggest that LHR is a strain- and mutagen-specific phenomenon and cannot be explained within the present knowledge of repair processes in yeast.


Host specificity of DNA in Haemophilus influenzae: DNA restriction enzyme from H. influenzae Rf232. A restriction endonuclease has been partially purified from Haemophilus influenzae Rf232 containing the genetically determined system of restriction and modification of DNA. The enzyme requires ATP for the degradation of transfecting phage DNA.