Germline mutations of the E-cadherin(CDH1) and TP53 genes, rather than of RUNX3 and HPP1, contribute to genetic predisposition in German gastric cancer patients.
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Animals↗
Biomedical subjects
K Biedermann
Publications and source records attributed to K Biedermann.
Prevention of vertical HIV transmission: additive protective effect of elective Cesarean section and zidovudine prophylaxis. Swiss Neonatal HIV Study Group.
OBJECTIVE: To study the effect of elective Cesarean section and zidovudine prophylaxis on vertical HIV transmission. DESIGN: Prospective study. SETTING: Obstetric and paediatric clinics in Switzerland. PARTICIPANTS: Children of mothers with HIV infection identified before or at delivery. INTERVENTIONS: Routine use of elective Cesarean section for HIV-infected parturients by some Swiss centres since 1985. National recommendation for zidovudine prophylaxis in mid-1994. MAIN OUTCOME MEASURE: HIV infection status of children. RESULTS: In a cohort of 494 children born at least 6 months before the analysis date, 67 out of 414 children with known infection status were found to be infected, giving an overall transmission rate of 16.2% [95% confidence interval (CI), 13.0-18.51. Elective Cesarean section with intact membranes and without previous labour was associated with a lower transmission rate of 6% [odds ratio (OR), 0.29; 95% CI, 0.12-0.70; P = 0.006 versus other delivery modes]. Transmission rate was intermediate after spontaneous delivery or non-elective Cesarean section (18%), and higher after obstetric interventions (27%; test for trend, P < 0.001). Since mid-1994, 78% of all women with registered pregnancies have received some form of zidovudine prophylaxis. Transmission rate was reduced from 17 to 7% after any zidovudine exposure (OR, 0.4; 95% CI, 0.11-1.41). Combined use of elective Cesarean section and zidovudine resulted in a 0% transmission rate (none out of 31), compared with 8% (seven out of 86) after elective Cesarean section without zidovudine, 17% (four out of 24) after zidovudine alone, and 20% (55 out of 271) after no intervention. CONCLUSIONS: Elective Cesarean section and zidovudine prophylaxis appear to have an additive effect in the prevention of vertical HIV transmission.
Abortion, Induced↗
Mathematical modeling of proteinase A overproduction by Saccharomyces cerevisiae.
A simple, structured model was developed to describe the growth and product formation behavior of two recombinant strains of Saccharomyces cerevisiae (JG176 and JG180), both overproducing extracellular proteinase A. The model parameters were estimated to data from continuous fermentations obtained at steady-state conditions. Model predictions show good agreement with experimental data obtained by batch fermentations. The two concerned organisms are distinguished from each other by the type of promoter on the plasmids controlling the proteinase A expression. The proteinase A transcription is controlled by the natural proteinase A promoter in JG176 and by a tpi promoter in JG180. By means of experiments and simulations, the extracellular product formation from the two strains with different promoter systems was compared in batch and continuous fermentations. The results showed that the proteinase A formation kinetic from JG176 was a combination of growth and nongrowth associated (production in the stationary growth phase), whereas the proteinase A formation from JG180 was truly growth associated (production in the exponential growth phase). In both batch and continuous cultivations JG176 gave the highest product concentrations and volumetric productivities.
Aspartic Acid Endopeptidases↗
The use of antibodies for characterization and quantification of a recombinant protein.
In this study, we characterized proteinase A secreted by recombinant Saccharomyces cerevisiae bearing a multicopy plasmid containing the encoding gene (PEP4). Polyclonal and monoclonal antibodies were raised to study the product heterogeneity. Characterization of proteinase A was performed by immunoelectrophoresis and immunoblotting techniques. None of the monoclonal antibodies raised against proteinase A was found to react with the glycosyl side chains; thus cross-reaction with other glycosylated proteins (e.g. carboxypeptidase Y) was very low. This study allowed us to develop an ELISA method for the quantification of proteinase A in culture supernatants as well as the evaluation of monoclonal antibodies for their use in immunoaffinity chromatography.
Animals↗
Production of proteinase A by Saccharomyces cerevisiae in a cell-recycling fermentation system: experiments and computer simulations.
Overproduction of proteinase A by recombinant Saccharomyces cerevisiae was investigated by cultivations in a cell-recycling bioreactor. Membrane filtration was used to separate cells from the broth. Recycling ratios and dilution rates were varied and the effect on enzyme production was studied both experimentally and by computer simulations. Experiments and simulations showed that cell mass and product concentration were enhanced by high ratios of recycling. Additional simulations showed that the proteinase A concentration decreased drastically at high dilution rates and the optimal volumetric productivities were at high dilution rates just below washout and at high ratios of recycling. Cell-recycling fermentation gave much higher volumetric productivities and stable product concentrations in contrast to simple continuous fermentation.
Aspartic Acid Endopeptidases↗
Lysozyme binds to elastin and protects elastin from elastase-mediated degradation.
Lysozyme has been shown to be associated with damaged elastic fibers in many tissues and organs. To better characterize this interaction, binding of lysozyme to elastin was studied using solution-based binding assays. Under physiologic conditions, radio-labeled lysozyme bound specifically to elastin in a time- and concentration-dependent manner. Binding was reversible and was inhibited by unlabeled human and hen lysozyme but not by other proteins. Lysozyme had no elastolytic activity as assessed by a standard tritium-release assay, but, importantly, prevented the proteolytic degradation of elastin by human leukocyte elastase, pancreatic elastase, thermolysin, and Pseudomonas elastase. A striking feature of lysozyme's anti-elastase activity was that it did not function in the classical sense of inhibiting directly the enzymatic activity of the protease. Instead, by binding to elastin, lysozyme prevented the protease from interacting with the elastin substrate in ways that normally favor proteolysis. These results show that lysozyme binds to the elastin component of elastic fibers and that this interaction has important biological consequences for elastic fiber degradation. By preventing degradation of elastin, lysozyme can function as an important natural inhibitor that exerts a protective effect on elastic fibers at sites of tissue injury.
Elastin↗
Sleep and the sleep electroencephalogram across the menstrual cycle in young healthy women.
Cyclic changes in hormones, body temperature, and metabolic rate characterize the menstrual cycle. To investigate whether these changes are associated with changes in sleep and the sleep electroencephalogram (EEG), a total of 138 sleep episodes from 9 women with no premenstrual syndrome symptoms were recorded every second night throughout one ovulatory menstrual cycle and analyzed in relation to menstrual phase. Ovulation and menstrual cycle stage were confirmed by measurements of temperature, urinary LH, and midluteal plasma levels of estrogen and progesterone. No significant variation across the menstrual cycle was observed for subjective ratings of sleep quality and mood as well as for objective measures of total sleep time, sleep efficiency, sleep latency, rapid eye movement sleep latency, and slow wave sleep. In nonrapid eye movement sleep, EEG power density in the 14.25-15.0 hertz band, which corresponds to the upper frequency range of the sleep spindles, exhibited a large variation across the menstrual cycle, with a maximum in the luteal phase. The data show that in healthy young women, sleep spindle frequency activity varies in parallel with core body temperature, whereas homeostatic sleep regulatory mechanisms, as indexed by the time course of EEG slow wave activity are not substantially affected by the menstrual cycle.
Body Temperature↗
[Pregnancy ultrasound screening in relation to the new health insurance regulation].
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Congenital Abnormalities↗
[HIV and pregnancy].
Since 1990 216 HIV-infected pregnant women have been enrolled in an ongoing nationwide study named "HIV and Pregnancy" financed by the Swiss Federal Office of Health (No. 90-7007 and 93-7131). Of a total of 228 recorded pregnancies 154 continued to parturition. Until now it has been definitively established whether or not 89 offsprings have been infected with HIV by their mothers. According to clinical and immunological findings most of the pregnant women are still in early, stable stages of HIV-infection (stages II and III of the CDC classification system in 94% of the subjects; mean CD4-cell count around 600/microliters). HIV infection was the consequence of an intravenous substance abuse in two thirds of the women. Detailed interviews revealed an alarming negligence with regard to compliance with safer sex recommendations and contraception. Advisory services of specialized AIDS information centers have very rarely been called on. In our group, the vertical transmission rate shows a statistically significant correlation with low maternal anti-HIV-p24 antibody titers, high serum neopterin- and IgA-concentrations, and also with the use of forceps and vacuum in vaginal delivery. Maternal substance abuse but not HIV infection itself resulted in an incidence of preterm deliveries roughly twice as high as in the normal Swiss population.
Abortion, Induced↗
Do neuroactive steroids cause fatigue in pregnancy?
To elucidate factors causing widespread fatigue in pregnancy we studied plasma samples from 23 healthy pregnant volunteers, measuring endogenous neuroactive steroids, endozepines and benzodiazepines by receptor binding assays. The samples were taken at different gestational ages and the women were asked about their feeling of fatigue at the time of sample collection. We found a significant correlation between fatigue in pregnancy and presence of neuroactive steroid-like activity, but could not detect endogenous benzodiazepine-like factors. These results suggest that neuroactive steroids may be involved in fatigue during pregnancy. Their site of synthesis and their biological role remain unclear.
Adult↗
Uremic small-artery disease with medial calcification and intimal hyperplasia (so-called calciphylaxis): a complication of chronic renal failure and benefit from parathyroidectomy.
BACKGROUND: Uremic small-artery disease with medial calcification and intimal hyperplasia can lead to life-threatening skin necrosis or acral gangrene. It is a distinct complication of chronic renal failure that must be differentiated from soft-tissue calcification. An increased calcium-phosphate product and secondary hyperparathyroidism are the main underlying conditions. The benefit of parathyroidectomy is controversial. OBJECTIVE: This article is based on a literature search to determine prognostic factors and, in particular, the benefit of parathyroidectomy. METHODS: The literature on uremic small-artery disease (so-called calciphylaxis) was reviewed (full data set: 104 cases, including five of our own). The therapeutic benefit of parathyroidectomy and the relation between prognostic predictors (localization, dialysis, and transplant) and outcome were analyzed. The relation between diabetes and acral gangrene was also examined. Further epidemiologic data on the reviewed group of patients were established. RESULTS: Thirty-eight of 58 patients who underwent parathyroidectomy survived compared with 13 of 37 patients who did not undergo parathyroidectomy (p = 0.007, n = 95). Forty of 53 patients with distal localization of necrosis survived compared with 11 of 42 patients with proximal pattern (p < 0.00001; n = 95). Dialysis and kidney transplantation followed by immunosuppression showed no relation to disease outcome. No association was found between diabetes and acral gangrene (p = 0.50). CONCLUSION: Uremic small-artery disease is a distinct complication of chronic renal failure. Its recognition and early diagnosis should allow more effective treatment. In our retrospective study parathyroidectomy was significantly related to survival. Only a randomized, controlled, prospective trial (parathyroidectomy vs conservative treatment of secondary hyperparathyroidism) can establish the value of parathyroidectomy in uremic small-artery disease.
Adult↗
[Pregnancies in HIV infected women in Switzerland].
In a national multicentre study, 229 pregnancies in 219 HIV-positive women were prospectively followed up between January 1, 1990, and October 30, 1993. 69.8% were infected by intravenous drug abuse and 91.5% were asymptomatic (CDC classes II and III) in early pregnancy. 48 (21.0%) were first discovered to be HIV-infected during the index pregnancy: 46 of these had risk factors. The present epidemiologic development does not seem to warrant a general HIV-screening in pregnancy at this time. 71 pregnancies (31%) were terminated; 158 children were born, 17 (23.3%) of the 73 definitely classified are HIV-infected. An asymptomatic HIV infection with a sufficiently high (> 200/microliters) CD4 cell count has no proven influence on the pregnancy. Otherwise, however, maternal infectious diseases can lead to prematurity. For mothers with i.v. drug abuse, there is a significantly higher incidence of prematurity and fetal growth retardation. The maternal HIV infection can be transmitted to the child either during pregnancy or at delivery. The incidence of vertical transmission in our study was 23.3%; the most predictive parameter for a prenatal HIV transmission is a low anti-p24 antibody titre. The risk of intrapartum transmission seems to be somewhat, but not significantly, reduced for primary Caesarean sections. Recently, prophylaxis with Zidovudin during pregnancy, beginning after the 14th GW, was found to reduce vertical HIV-transmission by 66%. Since the virus can also be transmitted through mothers' milk, HIV-positive mothers should not nurse their babies. Maternal infections are significantly more frequent in HIV-positive women, and are a risk factor for prematurity.(ABSTRACT TRUNCATED AT 250 WORDS)
Abortion, Induced↗
Pregnancy, immunosuppression and reactivation of latent toxoplasmosis.
Toxoplasmosis is a chronic, latent infection which can be reactivated in the presence of immunosuppression. The critical question in obstetrics is whether toxoplasmosis may be reactivated in the presence of the physiological "immunosuppression" of pregnancy. Standard in vitro tests, done in 24 healthy pregnant women and compared with the literature, show no significant changes in humoral and cellular immunity during pregnancy. However, the fact that some infections occur more frequently and more severely than in non-pregnant women (e.g. those due to cytomegalovirus (CMV) and human papilloma virus (HPV) points to a degree of pregnancy-associated immunosuppression. Non-rejection of the semiallogenic fetus is achieved in presence of maternal immunocompetence and is explained mainly by local changes in immune function, mediated by inhibitors of decidual, placental and fetal origin, and by the absence of class II histocompatibility antigens at the fetomaternal interface. Immune status allowing reactivation of toxoplasmosis was studied in a selected group of (predominantly male) AIDS patients from the Swiss HIV Cohort study. Shortly before (cerebral) reactivation of toxoplasmosis, 92% of these patients had very low CD4 lymphocyte counts (mean 50 cells/microliters, i.e. lower than ever recorded in a normal uncomplicated pregnancy). In a larger population of 48 women receiving immunosuppressive therapy after organ transplantation, not a single case of cerebral toxoplasmosis was observed during pregnancy, while in the 105 HIV-positive women in the Swiss HIV and Pregnancy study, there was only one case of cerebral toxoplasmosis during pregnancy and the puerperium (20 CD4/microliters), even though some 17% of those sampled (18/105) had CD4 levels below 200 cells/microliters on at least one occasion during pregnancy. These findings explain why latent toxoplasmosis is not reactivated in normal pregnancy, and why it is only likely in an immunosuppressed mother when her CD4 lymphocyte count is very low (< 200 cells/microliters). In such cases, a prophylactic treatment to prevent maternal reactivation and vertical transmission of toxoplasmosis may be useful.
AIDS-Related Opportunistic Infections↗
[Prevention of congenital toxoplasmosis in Switzerland. Consensus report of the study group "Congenital toxoplasmosis" of the federal public health office].
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Female↗
[Toxoplasmosis in pregnancy: prevention, prenatal diagnosis and treatment].
Maternal infection with Toxoplasma gondii acquired during pregnancy occurs in more than 500 women per year in Switzerland. Systematic screening at the beginning of pregnancy allows the introduction of health education programs. The screening during pregnancy is performed to diagnose primary maternal infections and to propose prenatal diagnosis and treatment. The administration of specific antibiotherapy during pregnancy (spiramycine or the association of pyrimethamine and sulfonamides) significantly reduces the risk of fetal infection. Prenatal diagnosis of congenital toxoplasmosis is possible and reliable. It avoids unnecessary termination of pregnancy when the fetus is not infected and specific therapy in case of infection (association of pyrimethamine and sulfonamides). Prenatal treatment may be proposed without prenatal diagnosis as of the 16th week of gestation. In any case, prenatal treatment seems to reduce the incidence of severe congenital toxoplasmosis.
Coccidiostats↗
[Prevention of congenital toxoplasmosis in Europe].
To sound out prevalent opinions among health authorities in Europe concerning the control and prevention of congenital toxoplasmosis (CT), a questionnaire was sent to the 28 WHO member countries in Europe. The questionnaire was returned by 23 countries. Only 7 countries recommend systematic screening of pregnant women. The reasons given by the 14 countries which do not recommend systematic screening are diverse: recommendations are in preparation, unfavourable cost-benefit return, absence of satisfactory treatment, programme not possible, incidence level too low, etc. 11 countries have a surveillance system for CT, of which only 3 are among the countries which recommend systematic screening. However, the absence of a multidisciplinary approach does not permit proper surveillance of cases. It appears from this survey that control of CT is undertaken in a very heterogeneous manner in Europe and no country has a programme whose impact on CT can be measured. So far, the European experience does not permit conclusions either in favour of or against a programme for the systematic screening of CT. However, cost-benefit analysis plays a very important role in determining whether such a programme should be implemented. Parameters such as the security of diagnosis (standardization of methods, quality and experience of the laboratories) and the monitoring of cases (definition, multidisciplinary approach to the surveillance and long-term treatment of patients, national collection of case reports, evaluation of the programme) are indispensable for the implementation of an effective surveillance system.
Cost-Benefit Analysis↗
[Nuclease isoforms of natural and recombinant strains of Serratia marcescens. Comparative characteristics of plasma desorption mass spectrometry].
The primary structure of isoforms of natural nuclease secreted by Serratia marcescens as well as of recombinant nuclease produced by Escherichia coli has been characterized by plasma desorption mass spectrometry. The isoforms were isolated from the purified nuclease on a DEAE-cellulose anion-exchange column and digested with endoproteinase Lys-C. The peptides generated were isolated by reversed phase IIPLC and their molecular masses determined by plasma desorption mass spectrometry. Among the nuclease isoforms secreted by parent cells, a new isoform, Sm3, was found. Comparison of the peptides yielded by nuclease Sm2 and two isoenzymes, Sm1 and Sm3, demonstrated their distinction only in the N-termini; three amino acids are lacking in Sm1 and one residue in Sm3. Identity was demonstrated between nucleases Sm1 and Sm2 produced by S. marcescens and the isoforms rSm1 and rSm2 secreted by the recombinant E. coli strain.
Amino Acid Sequence↗
[Characteristics of isoforms of Serratia marcescens from electrospray mass spectrometry].
Electrospray mass spectrometry was used to determine the molecular masses of nuclease isoforms isolated and purified from the cultural fluid of Serratia marcescens B10M1. The primary structure of each of the isoforms isolated from the nuclease preparations was established by comparing their masses with the known amino acid sequence encoded by the nuc-gene. The structure of some of these isoforms was verified by N-terminal sequencing, that of nearly all isoforms-by isoelectric focusing. All nuclease isoforms were found to be variants of native nuclease split at the molecular N-termini.
Chromatography, DEAE-Cellulose↗