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Biomedical subjects

S Koch

Publications and source records attributed to S Koch.

At least 199 records · Page 11Linked to original sources

HDL-cholesterol related to weight, smoking, and physical fitness in German Air Force pilots.

This study was undertaken to find out the importance of HDL-cholesterol in assessing coronary risk in our pilots. We related cholesterol, HDL-cholesterol, and the cholesterol/HDL-cholesterol ratio in blood to the BROCA-Index, smoking, and relative PWC 150 in 589 individuals. We found positive correlations between the cholesterol/HDL-cholesterol ratio to the BROCA-Index and to smoking. We did not find any correlation between cholesterol alone and the BROCA-Index or smoking. Moreover, we failed to find any correlations to physical fitness calculated from PWC 150. That may be due to the higher physical fitness standard in our pilots in comparison with the normal population. It is concluded, that a HDL-cholesterol determination is a more relevant parameter than cholesterol alone in borderline and elevated cholesterol levels.

Adult↗

The genetic organization of integrated hepatitis B virus DNA in the human hepatoma cell line PLC/PRF/5.

Hepatitis B virus (HBV) DNA is often found integrated in the genome of infected human liver cells and is supposed to be related to the development of primary liver carcinoma (PLC). Four clones of HBV DNA-containing sequences derived from DNA of the human PLC-derived cell line PLC/PRF/5 are discussed. The viral sequences show no intricate rearrangements excepting for a duplication and an inversion in one case, and a deletion in another. In all cases integration of the viral DNA was seen to be in a region which is single-stranded in the unintegrated HBV DNA. Sequence homologies between human and viral DNA flanking the integration sites have been detected. That may have a functional role in integration. Nucleotide sequence analyses of regions encompassing the viral-human junctions reveal open reading frames which consist of viral and/or human information. The possible expression of chimeric or cellular proteins may play a role in tumour development, and offers directions for further investigations.

Base Sequence↗

Cardiovascular findings in congenital contractural arachnodactyly: report of an affected kindred.

Three generations of a kindred had a history and physical findings consistent with congenital contractural arachnodactyly (CCA) segregating in an autosomal-dominant manner. Six of the seven affected patients we examined had mitral valve prolapse (MVP) diagnosed clinically or by echocardiography. The family members without CCA did not have MVP. This association of cardiac involvement with CCA further lessens the distinction between CCA and the Marfan syndrome. The indication for ophthamologic and echocardiographic follow-up of patients carrying the diagnosis of CCA is stressed.

Adult↗

Amplification and rearrangement in hepatoma cell DNA associated with integrated hepatitis B virus DNA.

DNA of hepatitis B virus is found to be integrated into the genome of infected human liver cells and may be related to the development of primary liver carcinoma. We have previously reported the cloning of cellular DNA with integrated HBV sequences from the PLC/PRF/5 cell line which derives from a human primary liver carcinoma. Two clones, designated as A-10.7 and A-10.5, and a third uncloned fragment are compared by restriction enzyme mapping, hybridization and nucleotide sequencing. The results indicate that amplification of integrated viral DNA and host flanking regions has occurred, followed by transposition and/or major deletions. The implications of these findings for the development of primary liver carcinoma are discussed.

Base Sequence↗

Gastric response to severe head injury.

We studied the gastric response to severe head injury and multiple trauma in 53 patients admitted to the surgical intensive care unit at the University of Louisville. Twenty-two of the 32 patients with severe head injury could have endoscopy. Each patient had gastritis or duodenitis. Patients with severe head injury had a slightly higher rate of gastric acid secretion than did the other trauma patients without severe head injury, but the difference was not significant. Serum gastrin levels were normal in both groups and did not correlate with intracranial pressure. Pancreatic polypeptide levels were significantly higher in patients with severe head injury compared with the control trauma patients without head injury. Elevations in pancreatic polypeptide may be linked to increases in intracranial pressure. We conclude that erosive gastritis occurs commonly in patients with severe head injury and that severe head injury is associated with a marked increase in pancreatic polypeptide levels in the fasted, nongut-stimulated state. Gastrin levels are within normal limits. Head injury appears to specifically increase pancreatic polypeptide release, probably by influencing autonomic centers in the mid brain. Because the cephalic phase of pancreatic polypeptide release is vagalcholinergic, the data are consistent with the hypothesis that severe head injury increases vagal activity. Participation of vagal adrenergic fibers in this process cannot be excluded.

Adolescent↗

Ethosuximide in epileptic women during pregnancy and lactation period. Placental transfer, serum concentrations in nursed infants and clinical status.

A total of 10 epileptic mothers treated with ethosuximide (ES) as well as their 13 newborns were included in this study. At birth foetal/maternal serum concentration ratios were 0.97 +/- 0.02 (n = 7) and ES half-lives in three neonates were 32, 37 and 38 h. The breast milk concentrations of ES were similar to those in maternal serum (milk/serum: 0.86 +/- 0.08, n = 12) and the nursed infants maintained serum levels between 15 and 40 micrograms/ml. Two major malformations (bilateral clefting, hare-lip) were observed in two neonates whose mothers received either ES/PB or ES/PMD comedication. The number of minor anomalies was higher in the ES group (6.2, n = 12) than in the pair-matched control group of infants born to non-epileptic mothers (2.1, n = 10). Neonatal behaviour complications occurred in seven infants, two of them were severely affected.

Abnormalities, Drug-Induced↗

Insulin and glucagon regulate cytosolic phosphoenolpyruvate carboxykinase (GTP) mRNA in rat liver.

Insulin causes a 7-10-fold decrease of both the mRNA that codes for rat hepatic phosphoenolpyruvate carboxykinase (mRNAPEPCK) and of PEPCK synthesis, provided the animals are made diabetic and fed chow. mRNAPEPCK, measured either by in vitro translation or cDNA hybridization, decreases with a half-time of 30-60 min after insulin treatment. This coordinant decrease, which approximates the half-life of mRNAPEPCK measured in a variety of situations, suggests that insulin acts by decreasing mRNAPEPCK production, and that the hormone does not alter the activity of a fixed amount of this RNA, or enhance its degradation. Glucagon results in a ninefold induction of mRNAPEPCK. Half-maximal induction occurs with doses between 20-75 micrograms/100 g body wt and occurs within 30-45 min. Maximal induction requires 150 micrograms/100 g body wt and occurs about 80 min after a single glucagon injection. N6,O2'-dibutyryl cAMP and a cAMP analogue that is not metabolized, 8-(4-chlorophenyl-thio)cAMP, induce mRNAPEPCK as effectively as glucagon and with similar kinetics. Since sodium butyrate, adenosine, and dibutyryl cGMP are ineffective inducers, cAMP appears to be the active agent in the hepatocyte.

Animals↗

Description of a murine B lymphoma tumor-specific antigen.

By using monoclonal antibodies, a tumor-specific antigen (TSA 41.5) was detected on the cell surface of a B lymphoma CH-1 tumor variant, CH-1.1. This antigen is not expressed by normal lymphocytes (spleen cells, lymph node cells, thymocytes, bone marrow cells, or blast cells) of B10.A mice, the host strain of CH-1.1, or by the CH-1 lymphoma. Immunoprecipitation and biochemical characterization of TSA 41.5 with the use of two-dimensional gel electrophoresis showed this antigen to be a surface protein of CH-1.1 cells with an Mr of 80k and pI of 4.6. TSA 41.5 is not related to the murine transferrin receptor, and not to gp70, a viral envelope protein expressed by CH-1.1 cells, shown by comparative peptide map analysis of these three proteins. TSA 41.5 is a surface antigen unique to the CH-1.1 tumor, which is not expressed by the 19 different murine tumor lines that were tested nor by spleen cells of 15 independent mouse strains. In addition, treatment of spleen cells with bacterial lipopolysaccharide did not induce the expression of TSA 41.5. These characteristics of TSA 41.5 make it unlikely to be a product of viruses. Additional evidence against TSA 41.5 being a viral protein was obtained by the observation that antisera against viral proteins could not block the binding of the anti-TSA monoclonal antibody to its antigen. In vitro treatment of CH-1.1 cells with anti-TSA monoclonal antibody specifically inhibited the in vitro growth of the tumor cells in a dose-dependent fashion. The CH-1.1 tumor and monoclonal antibodies could be a useful murine model system for the exploration of the use of monoclonal antibodies for the in vivo treatment of cancer.

Absorption↗

[Anti-epileptic agents during pregnancy. A prospective study on the course of pregnancy, malformations and child development].

In a prospective controlled study 70 children of females with epilepsy and on anticonvulsant medication during pregnancy were investigated. It was shown that epileptic females had stillbirths more frequently than expected. After delivery particularly children on phenobarbitone are sedated. Due to weak suckling this may lead to inadequate food intake. Withdrawal symptoms manifest in affected children as hyperexcitability lasting for weeks. Children of epileptic women on medication are generally smaller, of lower weight and have smaller heads than children from all control groups. Ingestion of more than one anticonvulsant leads to an even more pronounced reduction of infantile body measurements below the expected mean value. Small malformations are observed more frequently after intrauterine exposition to anticonvulsants than in the control groups. Ingestion of more than one anticonvulsant leads to an increase of the number of small malformations in the child than after single drug therapy. Children of epileptic parents are affected more frequently by large malformations than children of nonepileptic parents.

Abnormalities, Drug-Induced↗

Integration of hepatitis B virus DNA: evidence for integration in the single-stranded gap.

The DNA of hepatitis B virus (HBV) can integrate into the genomes of infected human liver cells and may be related to the development of primary liver carcinoma (PLC). This report describes the analysis of three integrated HBV DNA sequences cloned from DNA of the human PLC cell line PLC/PRF/5. In all these sequences, integration of the viral DNA is at a site that is single-stranded (gap) in the unintegrated HBV DNA. Contrary to some speculations, there are no large terminal redundancies flanking the inserts as found in retroviral proviruses. The viral sequences show no obvious rearrangements in these clones, but integration can be associated with deletions in the viral DNA and also apparently in the host DNA.

Base Sequence↗

Comparison of allogeneic and xenogeneic determinants on the H-2Kk molecule.

Two monoclonal rat anti-H-2 antibodies were derived by cell fusion from a rat immunized with mouse CH-1 lymphoma cells. Both antibodies recognize polymorphic H-2 determinants expressed on most haplotypes. Competitive binding studies on H-2Kk show that one rat antibody, R1-9.6, detects a determinant that is distant from the allodeterminants defined by 12 different mouse monoclonal anti H-2 antibodies. In contrast, the rat antibody R1-21.2 inhibits the binding of most mouse monoclonal anti H-2 antibodies to H-2k cells, possibly by causing a conformational change in the H-2 molecule. Both antibodies bind strongly to H-2 molecules and can be used for structural and biochemical studies.

Animals↗

Change of seizure frequency in pregnant epileptic women.

The effect of pregnancy on seizure frequency was monitored prospectively in 136 pregnancies of 122 epileptic women. Pregnancy did not influence the seizure frequency in 68 pregnancies (50%). In 50 pregnancies (37%) the number of seizures increased during pregnancy or puerperium. The seizure frequency decreased in 18 pregnancies (13%). In 34 out of 50 pregnancies (68%) the increase was associated with non-compliance with the drug regimen or sleep deprivation. In seven out of 18 pregnancies (39%) improvement was related to correction of non-compliance or sleep deprivation during the pregestational nine months. Insufficiently low plasma concentrations of antiepileptic drugs were found in 47% of the women with uncontrolled epilepsy during pregnancy. The course of epilepsy during pregnancy is primarily influenced by non-compliance, sleep deprivation during pregnancy, and inadequate therapy before and during pregnancy. With good medical attention pregnancy itself seems to have only a minimal influence on the course of epilepsy.

Adult↗

Teratogenic and pharmacokinetic studies of primidone during pregnancy and in the offspring of epileptic women.

Fourteen epileptic women treated with primidone, either alone or in combination with other antiepileptic drugs, were studied prospectively during their pregnancy. Plasma levels of primidone and its metabolites were monitored and correlated to findings in the offspring. Maternal serum concentrations of primidone and metabolites were generally low during pregnancy. The levels of its main metabolites--phenobarbital and PEMA--were found to drop within the first month of pregnancy in two cases. The plasma concentrations remained low until birth and rose sharply thereafter. The phenobarbital/primidone ratio (mean 0.84) and PEMA/primidone ratio (mean 0.56) in pregnant patients were found to be lower than in non-pregnant patients, except when primidone was given in combination with phenytoin in which case the expected phenobarbital/primidone (mean 2.5) and PEMA/primidone (mean 1.5) ratios were found. A ventricular septal defect was found in one of the offspring of the fourteen mothers and five children had microcephaly. There was a high incidence of poor somatic development with dystrophy (n=3) and short stature (n=2). Head circumferences (n=8), lengths (n=4) and/or weights (n=8) were below the 10th percentile in a number of children. Four children showed marked facial dysmorphy. Our preliminary data suggest that primidone intake during pregnancy may be important in the pathogenesis of minor anomalies and in the induction of poor somatic development.

Abnormalities, Drug-Induced↗

Influence of a blood component program on postoperative complication rates: a retrospective study in 372 patients.

We did a retrospective study of 372 thoracic and cardiovascular surgery patients, except open heart cases, which were treated by the same senior staff during the last year before (N = 197) and the first year after (N = 175) the introduction of a blood component program. There were no other basic changes of therapeutic policies. The two populations were comparable with respect to various basic characteristics. During the period 'before' the large majority of red cell units was 'deplasmatized' blood with a plasma deficit of 100 ml and a hematocrit of 40%. During the period 'after' it was red cell concentrates with a plasma deficit of 200 ml and a hematocrit of 70%. The usage pattern of red cell units did not change. The only statistically significant (and deliberate) quantitative difference between the transfusion regimens 'before' and 'after' was a more extensive intraoperative use of a gelatin plasma substitute to balance the plasma deficit of the red cell concentrates. As judged by various criteria, the postoperative courses of the patients 'before' and 'after' were virtually indistinguishable. We conclude that the blood component program practised at our hospital has no adverse effects on the postoperative course.

Adult↗

Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother's milk and clinical status in neonates of epileptic mothers.

The pharmacokinetics of valproic acid (VPA) and several metabolites were measured in 11 epileptic mothers and their 12 newborns. VPA was found in higher concentrations in cord serum than in maternal serum [(factor 1.7 +/- 0.6; (n = 6)]. VPA was excreted in the neonates with a mean half-life of 47 +/- 15 hr (n = 8) which is approximately 4 times the mean value found in adult epileptics. Maternal comedication (primidone and phenytoin) resulted in slightly reduced half-lives. The transplacental kinetics of the two main VPA metabolites in blood were similar to those of VPA. The very low levels of VPA in mother's milk (3% of maternal serum concentrations) suggest apparent safety of breast feeding. The [13C]aminopyrine breath test indicated neonatal hepatic enzyme activities which were slightly above those of unexposed neonates, but much below those of neonates which had been exposed to primidone and phenytoin in utero. Six of eight neonates exposed to VPA-monotherapy, but only one exposed to primidone or phenytoin comedication, developed an icterus neonatorum. A number of minor anomalies (four to eight per child) were observed, particularly hernias, diastasis of musculus rectus abdominis and weak abdominal walls. Two children were microcephalic and in another four children the head circumferences were below the 10th percentile. Significant withdrawal symptoms were not observed. Also hypoplasia of the nails and phalanges and facial dysmorphism associated with the "fetal hydantoin syndrome" did not occur in VPA-exposed children except in one case in which primidone had been administered as comedication.

Abnormalities, Drug-Induced↗