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Biomedical subjects

S Koch

Publications and source records attributed to S Koch.

At least 181 records · Page 10Linked to original sources
PubMed1989

Acute and chronic regulation of phosphoenolpyruvate carboxykinase mRNA by insulin and glucose.

Using the well differentiated rat hepatoma Fao we have studied the regulation of phosphoenolpyruvate carboxykinase (PEPCK) mRNA by insulin and glucose and compared these results to glucose production as estimated by glucose release into the medium. Fao cells possess an active gluconeogenic pathway and, when grown in glucose-free medium, release glucose for over 8 h. Addition of the cAMP analog, 8-(4-chlorophenyl-thio) cAMP (8-CTP-cAMP) or increasing the concentration of dihydroxyacetone and oxaloacetate results in an increase in glucose release which can be suppressed by insulin at concentrations between 1 and 100 nM. These effect of cAMP and insulin are associated with parallel changes in the level of mRNAPEPCK. Insulin treatment reduces mRNAPEPCK levels in these cells by 80%; this effect is transient reaching a maximum at 2-4 h. Addition of glucose to cells grown in glucose-free (G-) medium produces a decrease in mRNAPEPCK which is similar in magnitude and kinetics to that produced by insulin. Conversely, when cells grown in normal medium are placed in G- medium mRNAPEPCK levels triple over a period of 8 h, then return toward the basal value. Cells grown in G- medium or in G- medium plus 10nM insulin for 1 yr exhibit only slightly increased levels of mRNAPEPCK and respond to both 8-CTP-cAMP, and insulin, although the response to 8-CTP-cAMP is slightly blunted. These data indicate that glucose and insulin can play independent roles in regulation of PEPCK gene expression, and that these regulatory effects are usually transient.

Animals↗
PubMed1989

[Drug treatment of hyperlipidemia].

In the therapy of hyperlipemia nicotinic acid derivates, cholestyramine, fibrate derivates and HMG-CoA-reductase inhibitors are drugs of choice. The most important drugs of each group, the mode of action and the side effects are presented. In the therapy of hypercholesterolemia HMG-CoA-reductase inhibitors alone or in special cases in combination with low dose of cholestyramine are best qualified. For the treatment of hypercholesterolemia and hypercholesterolemia fibrate derivates are recommended.

Cholesterol, HDL↗
PubMed1989

[Mutagenicity testing in the sperm head test/mouse and mutagenic potency of 2 disinfectants on the basis of peracetic acid and phenols, respectively].

For the improvement of the registration of data by assessment of mutagenic risk the analysis of sperm-head abnormalities have been rendered as a suitable at indirect evidence of mutagenic potency. The reproduction of the results is well. The sensitivity of the test is high. The quantitative evaluation of genotoxic effects is possible. By reason of comparatively low methodical expense the screening investigations of species mouse are suitable, before more expensive tests will be accomplished for the elucidation of the mutation type. At 35 day-long intraperitoneal application the double number of sperm head abnormalities was approximately induced through Wofasteril (dose refer to main agent peracetic acid 2.6 mg/kg bw/d) and about 1/3 through cyclophosphamide (dose 25 mg/kg bw/d). With a 50% reduction of Wofasteril dose the mutagenic threshold-concentration was too low. The phenolic disinfectant Wofasept caused only slight no significant increase of the rate of sperm-head abnormalities (doses refer to the content of compounds, for Chlorocresol 1.6 mg/kg bw/d, for Clorofen 0.7 mg/kg bw/d and for detergent 4.8 mg/kg bw/d).

Acetates↗
PubMed1988

Immunological function of HLA-C antigens in HLA-Cw3 transgenic mice.

The human major histocompatibility complex encodes three classical class I antigens, HLA-A, -B, and -C. Of these HLA-A and -B act as strong transplantation antigens and as restriction molecules for recognition of foreign antigen by cytotoxic T lymphocytes. In contrast, little is known about HLA-C and it is not clear whether HLA-C has the same functional properties as HLA-A and -B. Transgenic C57BL/6 mice expressing the HLA-Cw3 gene were established. Functional studies demonstrated that transgenic skin was rapidly rejected by normal C57BL/6 mice and that cytotoxic T lymphocytes generated by immunization of the Cw3 transgenic mice with influenza and Sendai virus were restricted by the Cw3 molecule. These data suggest that HLA-Cw3 has immunological functions comparable to those of HLA-A and -B.

Animals↗
PubMed1988

Primidone and phenobarbital during lactation period in epileptic women: total and free drug serum levels in the nursed infants and their effects on neonatal behavior.

A total of 35 newborns whose mothers had been treated with either primidone (PMD), phenobarbital (PB) or a combination of one of these drugs with other antiepileptic drugs were included in this study. Fetal/maternal serum concentration ratios at birth, milk/serum concentration ratios and neonatal half-lives were determined for PMD, PB and phenylethylmalondiamide (PEMA). Steady-state serum levels of PMD in 2 nursed infants were 2.5 and 0.7 micrograms/ml, respectively, for PEMA values of 1.4 and 0.4 micrograms/ml. PB steady-state concentrations ranged between 2.0 and 13.0 micrograms/ml (6 infants). Maternal PB serum protein binding did not change during and after pregnancy. Neonatal free-fraction values at birth were similar to maternal values: 63.2 +/- 17.2% (n = 11). In the postnatal period, however, PB free-fraction values rose to more than 90% in some infants. In one case, neonatal free concentrations of PB were even higher during the 1st week after birth than the corresponding maternal values. Symptoms of sedation were observed in these neonates for which elevated free-fraction values of PB could be responsible. Behavior problems, such as withdrawal symptoms, were observed in neonates who eliminated PMD with short half-lives, while other infants with longer PMD half-lives or slower elimination because of nursing showed no such symptoms.

Behavior↗
PubMed1987

The production of recombinant HLA-DR beta and invariant chain polypeptides by cDNA expression in E. coli.

In this report we describe the production of recombinant fusion proteins of the HLA-DRw6 beta chain and the murine Ia-associated invariant chain. cDNAs encoding the human HLA-DRw6 beta chain and the murine Ia-associated invariant chain were introduced into bacterial expression plasmids. These plasmids direct the synthesis of the respective molecules as fusion proteins of the bacteriophage MS-2 polymerase by E. coli. Fusion proteins purified from crude E. coli lysates were used to raise antisera in rabbits. These antisera were able to immunoprecipitate biosynthetically labelled class II and invariant chain antigens. Additionally, two anti-DR antisera were raised against single domains of the HLA-DR beta chain thus generating reagents with a defined fine specificity. The anti-murine invariant chain serum was shown to cross-react with the human invariant chain and therefore may be useful for studying invariant chain and Ia antigen expression in different species. The method described here permitted us to produce large quantities of immunologically relevant proteins, for use in the production of polyclonal and monoclonal antibodies. Soluble fragments of the fusion proteins representing certain DR domains may also be useful in functional immunological studies.

Animals↗
PubMed1987

Expression of antibody cDNA in murine myeloma cells: possible involvement of additional regulatory elements in transcription of immunoglobulin genes.

Expression vectors for cDNA of the kappa and gamma 1 chains of a monoclonal antibody directed against creatine kinase were introduced into murine myeloma cells. Kappa and gamma 1 cDNA were either under the control of the SV40 early promoter or of the cognate promoters and enhancers of the light- and heavy-chain genes. Secretion of immuno-reactive kappa and gamma 1 chains into the culture medium was demonstrated with the SV40 promoter as well as with the cognate promoters. Expression of gamma 1 cDNA with the SV40 early promoter was about twice as high as with the heavy-chain promoter and enhancer. Expression of kappa cDNA under the control of the SV40 early promoter was about 17 times higher than with the light-chain promoter and enhancer. These expression levels were compared to those of a genomic immunoglobulin (Ig) kappa determinant, including introns. Such an entire kappa gene led to expression of the light chain at levels double those with the kappa cDNA construction using the SV40 promoter and about 35 times as high when using kappa cDNA and the cognate promoter and enhancer. This result might indicate that, besides the cognate promoter and enhancer elements, other intragenic elements are involved in the regulation of Ig expression. However, the SV40 early promoter seems to be able to compensate for the absence of these postulated regulatory elements probably located in the introns.

Animals↗
PubMed1986

Fetal growth, major malformations, and minor anomalies in infants born to women receiving valproic acid.

The association of fetal and neonatal distress, birth measurements, major malformations, and minor anomalies was studied prospectively in 14 infants of women with epilepsy who were receiving valproic acid (VPA) monotherapy and in 12 infants of women with epilepsy who were receiving VPA in combination with other anticonvulsant drugs. Comparison was made with 26 matched-pair controls and 116 controls from a larger study of antiepileptic drugs. During the first trimester, total VPA serum concentrations were well above therapeutic levels (100 to 184 micrograms/ml) in two women receiving high VPA doses (2000 and 1500 mg daily). Although dosage remained the same, serum concentrations decreased during pregnancy to therapeutic levels (33.9 to 57.0 micrograms/ml). The VPA percent free fraction increased in the third trimester and was threefold higher at birth. Almost half of the infants exposed to VPA monotherapy were distressed during labor, and 28% had low Apgar scores. Fetal and neonatal distress may be caused by the high VPA percent free fraction during labor and at birth. Mean body measurements at birth after VPA monotherapy were comparable to those in the matched control group, but were reduced in the group of infants receiving VPA combination therapy. Four infants exposed to VPA monotherapy were born with major malformations. The median number of minor anomalies was four times higher in infants whose mothers received VPA alone or VPA combination therapy than in controls. Seven infants had a pattern of craniofacial and digital anomalies that was distinctly different from that observed after in utero exposure to other anticonvulsant medications. The occurrence of major malformations and the number of minor anomalies may be dose related.

Abnormalities, Drug-Induced↗
PubMed1985

N-Ethyl-17(R,S)-methyl-(6aR,10aR)-delta 8-tetrahydrocannabinol-18-oic amide. Brain pharmacokinetics in mice, triglyceride/phospholipid partitioning and generalization to the discriminative stimulus properties of delta 9-THC in rats.

The title compound, designed as a model for the affinity moiety of a cannabinoid affinity gel was synthesized in tritiated form (sp. act. 7.27 mCi/mmole). To validate the affinity approach to isolate the putative THC receptor, the properties of the amide were studied. Upon i.p. injection in mice the amide reaches peak brain levels of 0.13% of the total dose after 15 min. Following i.v. injection, maximal brain concentrations of 1.9% are observed at 5 min. Compared to delta 9-THC, which distributes almost equally between triglyceride and phospholipid phases (51:49) the amide exhibits a strong preference for phospholipids (5:95) that can be interpreted as high relative membrane affinity. In rats trained in a water maze to discriminate between i.p. injections of 3 mg/kg delta 9-THC (ED50 = 1.8 mg/kg) and its vehicle, the amide was generalized to the training drug, being five times less potent (ED50 = 8.7 mg/kg) than delta 9-THC. This demonstration of cannabis-like activity indicates that the amide retains affinity to the postulated receptor and justifies the choice for the affinity ligand.

Animals↗
PubMed1985

Co-transcribed 3' host sequences augment expression of integrated hepatitis B virus DNA.

We have previously reported the cloning and structural analysis of integrated hepatitis B virus DNA copies from the human hepatoma cell line PLC/PRF/5. Here we show that the cloned DNA fragments of 10.7 kb and 10.5 kb contain intact coding sequences for HBsAg since Ltk- cells transfected with these DNAs secrete considerable amounts of HBsAg. We show for the 10.7-kb fragment that multiple readthrough messages composed of viral as well as cellular sequences are transcribed. These RNAs differ only in their 3' sequences. Furthermore, the 10.7-kb insert leads to a substantial increase in HBsAg produced compared with HBV DNA and with the 10.5-kb insert. We provide evidence that the different 3' sequences on the HBsAg transcripts account for the augmentation of expression.

Animals↗
PubMed1985

Action of (D-Pro4)-beta-casomorphin1-5 on processes of synaptic transmission.

The peptide (D-Pro4)-beta-casomorphin1-5 is a potent and long acting analgesic. Furthermore it is able to antagonize apomorphine-induced behavioral patterns, which are preferentially used as screening methods to detect dopaminolytic or neuroleptic properties. Because all of these tests do not exclude interaction of drugs with transmission systems other than the dopaminergic, biochemical studies were undertaken to estimate possible influences of the opioid peptide on processes of dopaminergic, serotonergic, and cholinergic transmission systems. In lower concentrations (D-Pro4)-beta-casomorphin1-5 enhances the potassium-stimulated release of acetylcholine from hippocampal slices and the basal overflow of dopamine from striatal slices. In high concentrations an augmentation of the potassium evoked release of dopamine and a reduction of the binding of [3H]spiperone on dopaminergic and serotonergic striatal receptors could be observed. These biochemical findings are discussed with regard to the behavioral patterns induced by this opioid peptide.

Acetylcholine↗
PubMed1985

Neonatal behaviour disturbances in infants of epileptic women treated during pregnancy.

Infants exposed in utero to antiepileptic drugs showed significantly more behaviour disturbances such as sedation (p less than 0.05) and hyperexcitability (p less than 0.01) than infants of a control group. The presence of these clinical symptoms and the time of their appearance did not seem to be dependent on the type of maternal medication, nor on the drug serum concentration in cord blood nor on the rate of drug disappearance from the infant's plasma.

Akathisia, Drug-Induced↗