Biomedical subjects

K Bauer

Publications and source records attributed to K Bauer.

At least 19 recordsLinked to original sources

PubMed1992

The primitive metazoan Hydra expresses antistasin, a serine protease inhibitor of vertebrate blood coagulation: cDNA cloning, cellular localisation and developmental regulation.

We have isolated and characterized cDNAs from Hydra which encode antistasin, a potent inhibitor of factor Xa in the vertebrate blood clotting cascade. Hydra antistasin is expressed in gland cells and represents a major class of transcripts from Hydra's head. Sequence analysis revealed that Hydra antistasin contains 6 internal repeats of a 25-26 amino acid sequence with a highly conserved pattern of 6 cysteine and 2 glycine residues identical to that in leech antistasin. Conservation of antistasin in a lower metazoan provides a potential link between the vertebrate and invertebrate coagulation systems.

Amino Acid Sequence↗

PubMed1992

[Bacterial studies on the occurrence of Mycobacterium paratuberculosis in fecal samples of zoo ruminants].

Mycobacterium (M.) paratuberculosis was isolated from fecal samples of 3 (21.4%) from 14 mouflons, of 10 (20.4%) from 49 dwarf goats, of 5 (14.3%) from 35 Cameroon sheep and of 1 (9.1%) from 11 alpine ibex. M. paratuberculosis could not found by cultural method in fecal samples of 22 Pinzgauer goats, of 15 bantengs, of 9 wild goats, of 9 skuddens, of 6 four-horned sheep, of 3 red-head sheep, and of 1 chamois. From all 19 animals with cultural positive fecal samples complement binding antibodies against M. paratuberculosis could not be found in the corresponding serum samples. The results confirm that M. paratuberculosis is more frequently in small zoo ruminants than up to now was suspected. The cultural examination of fecal samples has been proved to be a better method for detecting animal excretors than serological investigations by means of the complement fixation test.

Animals↗

PubMed1992

A2 domain of human recombinant-derived factor VIII is required for procoagulant activity but not for thrombin cleavage.

Thrombin treatment of the coagulation factor VIII results in a rapid activation of procoagulant activity with a subsequent first order decay. The structural requirements for thrombin-activated factor VIII were characterized using recombinant-derived human factor VIII and site-directed DNA-mediated mutagenesis. Thrombin-activated human recombinant-derived factor VIII was isolated in an active form by passage over Mono-S fast protein liquid chromatography. The peak fractions had a specific activity of 60,000 U/mg. The subunit composition in the peak fraction contained the 50-Kd A1 domain from the heavy chain, the 73-Kd light chain fragment, and trace amounts of the 43-Kd A2 domain. The requirement of domain A2 for functional activity was shown in several ways. First, the addition of an inhibitory monoclonal antibody that recognizes domain A2 destroyed factor VIIIa activity. Second, addition of a Mono-S FPLC fraction that contained the A2 domain polypeptide back to the peak activity fraction increased activity of the factor VIIIa by 22-fold. The maximum specific activity achieved was 180,000 U/mg. Finally, expression of an A2 domain deletion mutant did not yield procoagulant activity, although the mutant was effectively secreted from the cell, exhibited appropriate heavy and light chain association, and was susceptible to thrombin cleavage. Cotransfection of this A2 domain deletion mutant with an A2 domain expression vector yielded a secreted complex and restored procoagulant activity in the conditioned medium. This result shows that the A2 domain can fold and assemble with A2-deleted factor VIII to yield a functional molecule. We conclude that the A2 domain is required for functional factor VIIIa activity and loss of activity in activated factor VIII may result from dissociation of A2 from the thrombin-activated heterotrimer.

Antibodies, Monoclonal↗

PubMed1992

Spatiotemporal changes in Ha-ras p21 expression through the hepatocyte cell cycle during liver regeneration.

The protein product of the ras oncogene, Ha-ras (p21), is thought to be an important regulator of cell growth. The cytoplasmic relocalization of p21 in the cell during the cell cycle suggests a transient signaling role for this protein in association with its signal transduction function. Because of the importance of this role we examined spatial patterns in vivo of p21 expression at the protein and mRNA levels in hepatocytes during compensatory growth in rat liver following partial hepatectomy. A low level of p21 was immunolocalized on the cytoplasmic membrane of nonregenerating hepatocytes. The level of hepatic p21 increased significantly and without spatial restriction within the liver from 36 to 60 hr after partial hepatectomy (PH). p21 was localized in the cytoplasm of dividing hepatocytes and on the hepatic cytoplasmic membrane. The elevated p21 level decreased and was found mainly on hepatocyte plasma membranes by 96 hr after PH. Immunogold electron microscopy showed p21 localized over mitochondrial membranes and nuclei in nondividing regenerating hepatocytes. Approximately 50% of nonregenerating hepatocytes show nuclear localization of p21. This percentage changes with time following PH. The decrease in nuclear localization was accompanied with an increase in the low number of hepatocytes which demonstrated cytoplasmic localization in nondividing hepatocytes in regenerating liver. Flow cytometric analysis revealed a significant increase of p21 at 36 hr after PH which was 12 hr after the initial induction of ras mRNA. ras mRNA level increased 1.5-fold at 24 hr after PH and a maximum twofold induction was observed at 48 hr. Cell-cycle analysis of regenerating hepatocytes indicated a synchronized first peak of cell division 36-40 hr after PH. Dual parameter flow cytometry revealed that the level of p21 in hepatocytes in S phase and G2/M phase of the cell cycle was significantly higher than that in G0/G1 phase during regeneration. These findings suggest that p21 is important for the progression of regenerating hepatocytes to S phase and then to G2/M phase.

Amino Acid Sequence↗

PubMed1992

Urodilatin and atrial natriuretic peptide are present in the urine of healthy neonates and young infants.

Urine sampling has been proposed as noninvasive monitoring of plasma atrial natriuretic peptide (ANP) in neonates, assuming urine contains only filtered plasma ANP. Recently, urodilatin, another natriuretic peptide, which is cross-reactive to ANP in the ANP radioimmunoassay (ANP-RIA), has been isolated from the urine of adults. We studied the urine of healthy term neonates and young infants for the presence of urodilatin. In all urine samples, we found three peaks of ANP-RIA-reactive material: the first one in the position of urodilatin, the second one coeluting with synthetic ANP and a third late eluting peak, possibly containing degradation products. The physiological significance of these findings remains to be investigated.

Atrial Natriuretic Factor↗

PubMed1992

[Antibody prevalence for hepatitis C and other parenterally transmissible viral diseases in i. v. drug dependent patients].

Serum samples of 151 intravenous drug users were tested for markers of hepatitis B, hepatitis C, HIV and HTLV-I infection to estimate the prevalence of blood born virus infection in this high risk group. Anti HCV antibodies were found in 75% of sera. Seroprevalence for HIV was found 13%, for hepatitis B markers 68% and none for HTLV-I. Multiple infections have been very frequent.

Adult↗

PubMed1992

Inactivation of the thyrotropin releasing hormone.

Thyrotropin Releasing Hormone (TRH; pyroGlu-His-Pro-NH2) is rapidly hydrolyzed at the pyroGlu-His bond by a heterogeneously distributed ectoenzyme and a TRH-degrading serum enzyme. For these enzymes, the high degree of substrate specificity, the tissue specific hormonal regulation, the unusual tissue and the heterogenous cellular distribution strongly suggests that they serve very specialized functions for the transmission of TRH signals at specific target sites.

Animals↗

PubMed1992

Influence of HIV-1 infection and cigarette smoking on leukocyte profiles in homosexual men. The Multicenter AIDS Cohort Study.

The interaction between the effects of HIV-1 infection and cigarette smoking on leukocyte profiles was studied in 307 HIV-1 seroconverters in the Multicenter AIDS Cohort Study (MACS). Longitudinal data for white blood cell (WBC) counts, WBC differentials, T cell subsets, and smoking behavior were collected semiannually for up to 7 years. Prior to seroconversion, total WBC count increased in direct proportion to daily cigarette consumption, but this effect disappeared within 3 years of seroconversion. Analyses of WBC subsets (lymphocytes, monocytes, and granulocytes) and lymphocyte subsets (CD4+, CD8+ and non-T[CD3-]) showed that smoking had only minor effects on the proportions of these cells. In contrast, HIV-1 seroconversion was associated with a dramatic decrease in CD4+ lymphocyte percentage, a large increase in CD8+ lymphocyte percentage, a small increase in total lymphocyte percentage, and small decreases in the non-T lymphocyte and granulocyte percentages. These findings indicate that the effect of smoking on CD4 cell counts is (a) nonspecific, (b) maximal in seronegative individuals; and (c) lost by 3 years after seroconversion. Although the mechanism of the loss of smoking-induced leukocytosis after seroconversion remains to be determined, our results suggest that the effects of smoking are not likely to be important in the clinical use of leukocyte measurements, including measurements of CD4 lymphocytes, in individuals who have been HIV-1 seropositive for more than 3 years.

CD4-CD8 Ratio↗

PubMed1992

[HDL cholesterol as a sensitive diagnostic parameter in malaria].

In patients with malaria the lipid parameters triglycerides, cholesterol, and HDL-cholesterol were determined routinely. At the time of admission hypertriglyceridemia, hypocholesterolemia, and an extreme decrease in HDL-cholesterol were found. This dyslipoproteinemia was present in cases of falciparum malaria, as well as in cases of benign tertian malaria. The extent of HDL-cholesterol decrease showed no correlation to the severity of the clinical course of disease. HDL-cholesterol has proven to be an independent diagnostic laboratory finding in cases of suspected malarial infection. This parameter displays high diagnostic sensitivity, but no specificity for malaria.

Adult↗

PubMed1991

Combination of high-performance liquid chromatography and radioimmunoassay for the measurement of urodilatin and alpha-hANP in the urine of healthy males.

Urodilatin (ANP-(95-126)), a natriuretic peptide in urine, and alpha-hANP (ANP-(99-126)) are crossreactive in the radioimmunoassay of alpha-hANP (ANP-RIA). We therefore developed a method to separate physiological amounts of urodilatin and alpha-hANP in urine by high-performance liquid chromatography (HPLC) followed by ANP-RIA of the separated fractions. We studied urine samples of 10 healthy adult males with a plasma alpha-hANP level of 41 +/- 21 pg/ml (mean +/- SD) and a total urinary ANP-RIA reactivity of 40 +/- 21 pg/ml. In all urine samples we found three peaks of ANP-RIA reactivity, the first one coeluting with synthetic urodilatin, the second one with the retention time of alpha-hANP and a late eluting ANP-RIA-reactive peak, possibly containing degradation products. The ratio of urodilatin/alpha-hANP was 0.77 +/- 0.17.

Adult↗

PubMed1991

Body composition, nutrition, and fluid balance during the first two weeks of life in preterm neonates weighing less than 1500 grams.

To determine whether body weight during the first 2 weeks of life in preterm infants weighing less than 1500 gm reflects nutritional status or fluid balance, we studied total body water (TBW) (deuterium oxide dilution), extracellular volume (sucrose dilution), and plasma volume (Evans blue dilution), together with intake-output studies of nitrogen, fluid, and sodium on day 1 (median age 0.3 day), at a weight loss of 7.8% of birth weight (median age 3.4 days), and after birth weight was regained (median age 8.9 days) in eight clinically stable preterm infants (birth weight 810 to 1310 gm, gestational age 26 to 30 weeks) receiving ventilatory support. During the initial weight loss we found no evidence of catabolism. Body solids (weight--TBW) remained unchanged, there was nitrogen retention, and energy intake was sufficient to meet energy expenditure by day 2. However, we found evidence of fluid loss: TBW (mean +/- SD, -95 +/- 99 ml), extracellular volume (-98 +/- 63 ml), and interstitial volume (-102 +/- 75 ml) decreased significantly, indicating negative fluid and sodium balances. Blood volume and plasma volume remained unchanged. With the regaining of birth weight there was no increase in body solids despite a high degree of nitrogen retention, but there was a positive fluid balance although no significant increase in any body fluid compartment was found. We conclude that the observed postnatal weight changes reflect changes in interstitial volume.

Body Composition↗

PubMed1991

Assessment of systemic effects of different ophthalmic beta-blockers in healthy volunteers.

Systemic beta-blockade after single doses of ophthalmic beta-blockers (one drop in each eye) was investigated in healthy volunteers in two randomized, double-blind, crossover, placebo-controlled studies. beta-Blockade was evaluated by displacement of the bronchodilator (specific airway conductance), positive chronotropic (heart rate), and tremorogenic (finger tremor amplitude) dose-response curve for inhaled isoproterenol. In study 1, 0.5% betaxolol, 0.6% metipranolol, and 0.5% timolol were tested in 16 subjects. Compared with placebo, all beta-blockers resulted in a significant systemic beta-blockade (p greater than 0.05); the increasing order of potency was betaxolol, metipranolol, and timolol. In study 2, 2% butylamino-phenoxy-propanol-acetate (BPPA; a noncardioselective but topically oculoselective drug) and 1% timolol were investigated in 12 subjects. Placebo and BPPA showed no differences (p greater than 0.05), whereas timolol resulted in a significant beta-blockade (p less than 0.05). Topical oculoselectivity is an important aspect of drug safety of beta-blocking eyedrops. Measure of tremor is appropriate to evaluate beta 2-blockade.

Adrenergic beta-Antagonists↗

PubMed1991

Multilocular cystic renal cell carcinoma.

Multilocular cystic renal cell carcinoma (MCRCC) appears to be a distinct subtype of renal cell carcinoma with characteristic gross and microscopic features. The authors' ten-year experience (1977-1987) included six cases of MCRCC that were followed for a minimum of two years, with neither recurrence nor metastasis observed in any of the cases. During this period, there were 855 urologic procedures for the upper urinary tract, with 256 neoplasms or cysts identified. These included 32 simple cysts, 41 transitional cell carcinomas, 133 renal cell carcinomas, 17 papillary renal cell carcinomas, and 33 miscellaneous tumors. Histologically, the MCRCCs were well-demarcated multicystic lesions containing variably sized aggregates of neoplastic clear cells showing grade 1 nuclear features and little or no mitotic activity. The cyst walls were densely fibrotic, and the lining was often devoid of epithelium. Flow-cytometric analysis performed in five of the six cases with the use of paraffin-embedded tissue showed the tumors to be diploid in all instances, with low proliferative activity. The authors believe that this tumor is a low-grade variant of renal cell carcinoma and should be studied further to determine appropriate therapy.

Aged↗

PubMed1991

Creatine kinase determination: a European evaluation of the creatine kinase determination in serum, plasma and whole blood with the Reflotron system.

We evaluated a new dry-reagent carrier system for the determination of creatine kinase (EC 2.7.3.2) activity, Reflotron CK, with special attention to analytical performance with whole blood. We found a good within series imprecision. The median coefficient of variation was 3.1% for Reflotron CK (blood, serum and plasma) and 0.9% for the automatic analysers (serum and plasma only). The between-days imprecision with Reflotron CK (median CV: less than or equal to 3%) was similar to that for the comparison method on different analysers. Fresh samples of human blood, plasma and serum were examined by Reflotron CK and by a N-acetylcysteine activated creatine kinase method in six different clinical laboratories and in the Evaluation Department of Boehringer Mannheim GmbH. The correlation between these methods was excellent (r greater than or equal to 0.99), the median systematic deviation (bias) for all samples being smaller than -5%. Haematocrits between 0.25 and 0.50, haemolysis up to 6 g/l haemoglobin, and icteric samples with bilirubin concentrations up to 0.2 g/l showed no interference. No drug in therapeutic concentration was found to affect the Reflotron CK results; ascorbic acid, calcium dobesilate and sulphamethoxazole lowered the values only when present in high concentrations. Reflotron CK may be considered as a suitable alternative for decentralized testing sites, especially in situations where creatine kinase results are needed quickly.

Autoanalysis↗

PubMed1991

[Postnatal weight loss in ventilated premature infants below 1500 g: significance of renal and extra-renal fluid loss].

In 9 ventilated preterm infants (birth weight 810-1310 g, gestational age 26-30 weeks) we measured total body water (D2O dilution), extracellular volume (sucrose dilution) and renal function parameters at birth and when postnatal weight loss exceeded 5% of birth weight together with day to day changes of weight, fluid balance, and serum electrolytes. A significant postnatal weight loss (-89 +/- 47 g) occurred together with a reduction of total body water (-102 +/- 95 ml) and extracellular volume (-98 +/- 59 ml) in the first three days of life. The intracellular volume did not change. At the same time fluid balance was negative due to a high extrarenal water loss on day 1 and an increasing diuresis on the following days. The serum sodium concentration remained unchanged during postnatal water loss, because the negative fluid balance was accompanied by a negative sodium balance.

Birth Weight↗

PubMed1991

Flow cytometric DNA analysis of normal and pathologic parathyroid glands.

Assessment of cellular DNA content and cell cycle analysis by flow cytometry has been useful in predicting patient survival and the malignant potential of many neoplasms. In this study, we analyzed the DNA content and cell cycle distribution of 12 parathyroid adenomas, 15 carcinomas, 5 secondary hyperplasias, and 14 normal parathyroid glands. Appropriate areas demonstrating the pathologic changes were dissociated from paraffin-embedded, formaldehyde-fixed tissue for this purpose. All the cells from normal glands were diploid with mean and median S-phase fractions of 1.2% (range, 0.3-2.7%). Of the 18 glands from five patients with secondary hyperplasia, 4 (22%) had some cells which were aneuploid (from three patients), and 14 (78%) had only cells with a diploid DNA content. Mean and median S-phase fractions were 0.8% (range, 0.3-1.5%). One (8%) of the adenomas was tetraploid, 3 (25%) were aneuploid, and 8 (67%) were diploid. The mean S-phase fraction was 1.5% (range, 0.3-3.8%). Four (27%) of the carcinomas had tetraploid cells, 6 (40%) had aneuploid cells, and 5 (33%) had only diploid cells. Carcinomas had a mean S-phase fraction of 6.0% (median, 5.3%; range, 1.4-14.1%). This study indicates that DNA aneuploidy or tetraploidy may be present in many abnormal parathyroid entities, but not in normal parathyroids. Proliferative activity when considered with the DNA index may be a helpful adjunct in separating carcinomas from adenomas or hyperplasias.

Adenoma↗

PubMed1991

Double-blind randomized clinical trial on imidazole salicylate vs ibuprofen in osteoarthritis.

Imidazole salicylate (750 mg t.i.d.) was compared with ibuprofen (400 mg t.i.d.) in a 60-day double-blind parallel group clinical trial in 31 patients with osteoarthritis. Both drugs were effective in relieving joint pain and in reducing the duration of morning stiffness. A statistically significant reduction of the severity of these symptoms was observed already one week after the start of treatment, lasting until the end of the study. No significant differences in efficacy were demonstrated between the two drugs throughout the trial. The systemic tolerability, assessed by changes in tests of hematological, liver and kidney function, urinalysis and faecal occult blood was excellent with both treatments. The incidence of side effects (mostly gastrointestinal complaints) was fairly low in both groups, and less severe in the group treated with imidazole salicylate.

Adult↗

PubMed1990

Pulmonary effects of long-term beta 2-blockade in healthy subjects: comparative study of metoprolol OROS.

The effects on airway response of metoprolol OROS (oral osmotic) and three other long-acting beta-adrenoceptor blockers were studied. This was a placebo-controlled, randomized, five-period, single-blind, crossover trial in 15 healthy volunteers. Bronchial beta-blockade was estimated as the displacement of the salbutamol bronchodilator response of specific airway conductance (SGAW) measured by whole-body plethysmography. Metoprolol OROS (14/190 mg), slow-release (SR) metoprolol (200 mg), atenolol (100 mg), long-acting (LA) propranolol (160 mg), and placebo were given once daily for 7 days. Inhaled salbutamol was administered at peak drug levels in cumulative doses of 12.5 to 800 micrograms on day 5 and in a single dose of 400 micrograms on day 7. On day 5, salbutamol induced significant increases in SGAW in each treatment group. SGAW increased after the single dose of salbutamol on day 7 in all groups and then declined steadily. The highest values were found after placebo and metoprolol OROS, with smaller increases after SR metoprolol, atenolol, and LA propranolol, the latter showing the smallest increase. Therefore, it would appear that under steady-state conditions, beta 2-bronchial receptors are least blocked by metoprolol OROS, followed by SR metoprolol, atenolol, and LA propranolol.

Administration, Oral↗