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Biomedical subjects

R Köhler

Publications and source records attributed to R Köhler.

At least 19 recordsLinked to original sources
PubMed1995

The effects of desipramine on thyroid hormone concentrations in rat brain.

The effects of the antidepressant desipramine on the tissue concentrations of thyroxine and triiodothyronine in 9 different regions of the brain and also in the pituitary and liver were investigated in male rats. The investigations were carried out at three different times of the light/dark cycle: 5 a.m., 1 p.m. and 11 p.m. After fourteen days' treatment with 20 mg/kg/day desipramine by gavage the concentrations of triiodothyronine in the frontal and parieto-occipital cortex were significantly higher than in the saline-treated controls, those in the hippocampus lower and those in the 6 remaining brain regions the same. In 8 areas of the brain the concentrations of thyroxine were lower in the desipramine-treated rats and the tissue ratios of triiodothyronine to thyroxine were enhanced in 6 regions. These effects are most likely the result of the action of desipramine on the activity of the isoenzyme 5'II deiodinase. This enzyme catalyzes the deiodination of thyroxine to triiodothyronine in rat brain and its activity has recently been reported to be enhanced by desipramine. The observed effects were dose-dependent and also strongly dependent upon the time within the 24 h light/dark cycle at which the hormone concentrations were measured. No effects of desipramine were seen in the pituitary or liver after 14 days' treatment, or in various areas of the central nervous system 24 h after administration. In view of the psychotropic properties of thyroid hormones, it seems possible that the observed increases in triiodothyronine concentrations, particularly in cortical areas, are involved in the mechanisms of action of desipramine.

Administration, Oral↗
PubMed1995

Monomeric and dimeric forms of soluble receptors can differ in their neutralization potential.

Recombinant soluble forms of transmembrane receptors can be produced in monomeric and dimeric versions. Binding affinity and neutralization potential of these different forms of soluble receptors depend on the quaternary structure of their ligands. Monomeric ligands will be bound with equal affinity by both forms, whereas trimeric ligands, e.g. members of the tumor necrosis factor family of ligands, interact with much higher affinity with dimeric soluble receptors than with monomeric ones.

Amino Acid Sequence↗
PubMed1994

Hypothalamic-pituitary-thyroid axis in chronic alcoholism. II. Deiodinase activities and thyroid hormone concentrations in brain and peripheral tissues of rats chronically exposed to ethanol.

Thyroxine (T4), triiodothyronine (T3) concentrations, and the activities of the three deiodinase isoenzymes were measured in different brain regions and peripheral tissues of rats. According to an animal model of alcohol addiction, "behaviorally" dependent rats having lost control over their intake of ethanol were compared with alcohol-naive controls and ethanol-experienced, but "controlled" consumers. The two kinds of alcohol-experienced rats were investigated either 24 hr or 3 months after ethanol withdrawal. The results of these four groups were compared with those of an ethanol-naive control group. During withdrawal, the activities of type II 5'-deiodinase (which catalyzes deiodination of T4 and T3 in the CNS) in both the "behaviorally dependent" rats and the "controlled drinkers" were significantly lower than in the alcohol-naive controls in the frontal cortex, parieto-occipital cortex, hippocampus, and striatum, but not in the cerebellum or pituitary. Probably as a result, the tissue concentrations of T4 were higher in areas of the CNS in the groups exposed to alcohol. However, the T3 concentrations were normal. No relevant differences were seen between the activities of type III 5-deiodinase (which catalyzes the further deiodination of T3) observed in these groups. After 3 months of abstinence, the type II 5'-deiodinase activities had almost returned to normal in both "controlled drinkers" and "behaviorally dependent" animals, whereas type III 5-deiodinase activity was inhibited, possibly to maintain physiological concentrations of T3 during abstinence. Indeed, the tissue levels of T3 were normal in the areas of the CNS, and the T4 levels were still elevated. However, the liver concentrations of T3 and T4 were significantly lower in the "behaviourally dependent" animals than in the "controlled" drinkers after 3 months of abstinence, whereas no differences were found between the T4 and T3 concentrations in the areas of the CNS investigated in the two groups exposed to ethanol. These results suggest that chronic administration of ethanol affects intracellular thyroid hormone metabolism in both rat CNS and liver in the highly complex manner. No direct evidence of ethanol-induced enhancement of tissue uptake or concentrations was obtained. However, taking into account the numerous similarities between the clinical picture of hyperthyroidism and the symptomatology of alcoholism, it may be hypothesized that ethanol may directly influence any step in the as yet unknown biochemical cascade of thyroid hormone function.

Alcoholism↗
PubMed1994

The influence of desipramine on thyroid hormone metabolism in rat brain.

The effect of the antidepressant desipramine (DMI) on the activities of the three iodothyronine deiodinase isoenzymes involved in the central metabolism of thyroid hormones were investigated in 11 brain regions and 3 peripheral tissues in the rat. The investigations were carried out at three different times during the light/dark cycle: 5 A.M., 1 P.M. and 11 P.M. Interest is focused on changes in the two enzymes that catalyze: i) the 5'deiodination of T4 to the biologically active T3, i.e., type II 5'deiodinase (5'D-II), and ii) the 5 (or inner-ring) deiodination of T3 to the biologically inactive 3,3'T2, i.e., type III 5 deiodinase (5D-III). Fourteen days' treatment with 20 mg/kg DMI, but not with 5 mg/kg DMI, induced significant increases in 5'D-II in eight different areas of the CNS. The regions affected were identical to those that receive noradrenergic input from the locus coeruleus. Even control animals showed a circadian rhythm of 5'D-II activity in some brain regions, and the effects of DMI also depended on the time of death within the 24-hr rhythm. 5D-III was not affected. Serum T4 were lower after administration of DMI, most probably because of enhanced tissue uptake of T4. This is in line with the corresponding finding in depressed patients, indicating that similar changes in both central and peripheral thyroid hormone metabolism may occur after antidepressant pharmacotherapy in both humans and rats. These data support the hypothesis that interactions with the CNS metabolism of the thyroid hormones may be involved in the mechanisms of action of DMI.

Animals↗
PubMed1993

The influence of sleep deprivation on thyroid hormone metabolism in rat frontal cortex.

The effects of 24 h sleep deprivation (SD) on central thyroid hormone metabolism were investigated in rat frontal cortex. SD induced a significant rise in the activity of iodothyronine type II 5'-deiodinase (5'D-II), which catalyzes the conversion of thyroxine (T4) to triiodothyronine (T3) in the rat central nervous system (CNS). Tissue concentrations of T4 remained unchanged, whereas levels of T3 increased to more than 150% of the corresponding levels measured in control rats. Serum concentrations of T4 and T3 were also significantly enhanced by SD--an effect that has previously been described in depressed patients having undergone the same procedure. These results suggest that SD can dramatically increase T3 concentrations (and possibly function) in rat CNS. Whether or not these findings are of relevance in regard to the well-known antidepressant effect of SD in psychiatric patients with major depressive disorders remains to be established.

Animals↗
PubMed1993

Exogenous and endogenous contributions to nitrogen fluxes in the digestive tract of pigs fed a casein diet. III. Recycling of endogenous nitrogen.

The aim of the present study was to measure the incorporation of infused 15N in blood fractions, urine, digesta, faeces and in the exocrine pancreatic and biliary secretions, in order to estimate the endogenous part of nitrogen in the ileal digesta and in the faeces of pigs fed a casein diet and to calculate the total endogenous nitrogen secretion as well as its recycling in the digestive tract. For 8 d 11 Large White female pigs (50.1 +/- 1.8 kg) received a continuous infusion of L-[15N]leucine via a catheter in the jugular vein. The 15N-enrichment was measured in several fractions. The 15N-level of the pancreatic juice was higher than that in the biliary secretion, TCA-blood fractions, and urine during the whole experimental period. Using the 15N-isotope dilution method it was found that casein was completely digested up to the terminal ileum and that all the nitrogen in the ileal digesta was of endogenous origin. The total endogenous secretion was estimated at approximately 11 g N/d. The reabsorption of endogenous nitrogen amounted to 79% up to the end of the small intestine and 88% over the whole digestive tract.

Absorption↗
PubMed1992

Chimeric prion protein expression in cultured cells and transgenic mice.

The efficient expression of exogenous prion protein (PrP) molecules in mouse neuroblastoma cells that are chronically infected with murine scrapie prions (ScN2a cells; Butler, D.A., et al., 1988, J. Virol. 62, 1558-1564) and in transgenic mice is described. This technology allows investigation of the PrP molecule for structural regions involved in determining species specificity, as well as ablation experiments designed to address the functionality of particular regions of the PrP molecule. Previous reports demonstrated that the PrP gene specifies the host range for susceptibility of transgenic animals to prions (Scott, M., et al., 1989, Cell 59, 847-857; Prusiner, S.B., et al., 1990, Cell 63, 673-686). Consistent with these results, we showed that Syrian hamster (SHa) PrP is ineligible for efficient conversion to PrPSc in ScN2a cells. By constructing a series of chimeric mouse (Mo)/SHaPrP genes, we developed an epitopically tagged functional variant of the MoPrP gene, which can efficiently form protease-resistant PrP molecules upon expression in ScN2a cells. The presence of a defined epitope for an SHa-specific monoclonal antibody allows the products of this chimeric gene to be discriminated from endogenous MoPrP and creates a useful reagent for exploring structure/function relationships via targeted mutagenesis. In addition, we developed a transgenic mouse expression vector by manipulation of an SHaPrP cosmid clone. This vector permits the efficient expression of foreign PrP genes in the brains of transgenic animals, enabling pathological consequences of in vitro mutagenesis to be studied.

Animals↗
PubMed1991

Exogenous and endogenous contributions to nitrogen fluxes in the digestive tract of pigs fed a casein diet. II. Ileal and faecal digestibilities and absorption of amino acids.

The present work aimed at quantifying nitrogen (N) and amino acid (AA) fluxes in the digestive tract of growing pigs fed a casein diet. In this paper we report on digesta passage at the terminal ileum, on apparent balances at the ileal and faecal levels, and on nutrients appearance in the portal vein. Digesta flow-rate at the terminal ileum was maximum between 6 and 12 h after the meal. About 10% of N and 5% of total AA ingested were recovered within 24 h. AA absorption started 30 min after the meal, and was measurable until 13 to 14 h. The total AA absorbed in 24 h accounted for 128% of the AA ingested. The AA composition of ileal digesta was very different from that of casein, closely resembling that of endogenous proteins. The AA composition of faeces was very close to that of bacterial proteins. The ileal digestibilities of AA, though lower than their faecal values, were very high. This was confirmed by AA absorption balances greater than 100%. These data suggest that casein was almost totally digested by the terminal ileum, and that endogenous AA were substantially reabsorbed. These findings are supported by data on endogenous N recycling (15N), reported in a following paper.

Amino Acids↗
PubMed1991

A rabies-specific human monoclonal antibody that protects mice against lethal rabies.

According to a recommendation from WHO (World Health Organisation) for prevention of a possible rabies infection, active vaccination has to be combined with application of immunoglobulin to get a fast protective effect. At present, preparations of purified human or equine rabies-specific immunoglobulin are used. We have generated a human rabies-specific monoclonal antibody (huMAb) by immortalization of human B-cells with Epstein Barr Virus (EBV), followed by fusion with a mouse myeloma cell. The resulting clone TW-1 secrets an IgG1 lambda huMAb which specifically reacts in ELISA with 5 laboratory rabies virus strains of serotype 1 and DUV3 (Duvenhage, serotype 4). Western Blot analysis revealed fine specificity for the G glycoprotein (gp67) of rabies virus. HuMAb TW-1 neutralizes rabies virus in vitro (RFFIT) as well as in vivo and protects rabies infected mice. Compared to polyclonal human rabies immunoglobulins, huMAb TW-1 is advantageous, because of its defined specificity and the very low amounts of total protein needed for therapeutic effects.

Animals↗
PubMed1990

Escherichia coli-derived envelope protein gD but not gC antigens of herpes simplex virus protect mice against a lethal challenge with HSV-1 and HSV-2.

Immunization studies with HSV-1 and HSV-2 envelope proteins expressed in Escherichia coli were performed. After active immunization of mice with a gD-1 antigen (Leu53-Ala312) expressed as a fusion protein, the animals were protected from a lethal challenge with HSV-1 and HSV-2. In addition, antisera from rabbits immunized with the same gD-1 antigen also conferred passive immunity to mice against a challenge infection with either HSV-1 or HSV-2. In contrast to these successful gD-1 protection experiments, various gC-1 and gC-2 fusion proteins from E. coli failed to induce protective immunity. Moreover, the mice sera from immunized animals were not able to react with the authentic, glycosylated gC-1 and gC-2 envelope proteins, whereas sera raised against authentic gC-1 and gC-2 glycoproteins do recognize the gC fusion proteins from E. coli. These results indicate, that E. coli might represent an ideal system for expressing gD antigens as a possible component of a HSV vaccine, whereas gC antigen cannot be produced in an immunocompetent form in E. coli.

Animals↗
PubMed1990

[A modified Sarafoff suture for closure of the uterine wound in Cesarean section].

Using a retrospective investigation the authors demonstrate the advantage of the modified Sarafoff-suture (a one layer suture of the myometrium) in comparison with the two-layer suture. The results shows a lower rate of febrile courses, less postoperative complications and a shorter hospital stay. The first clinical experiences showed less scar complications in the courses of vaginal delivery in patients with a previous caesarean section. Therefore, the authors advise the modified Sarafoff-suture for wound closure in caesarean section.

Cesarean Section↗
PubMed1989

Blood levels of glucometabolic hormones and urinary saturation with stone forming phases after an oral test meal in male patients with recurrent idiopathic calcium urolithiasis and in healthy controls.

Male patients with recurrent calcium (Ca) urolithiasis (RCU) with idiopathic hypercalciuria (I-HC, n = 12) or normocalciuria (NC, n = 12), and age, sex, and weight-matched controls (C, n = 12) were evaluated before and after a carbohydrate-rich synthetic meal for blood glucose, free fatty acids (FFA), alpha-amino-nitrogen, several glucometabolic hormones and parathyroid hormone (PTH), and urine Ca, phosphate, oxalate, and cyclic adenosine monophosphate (cAMP) levels as well as saturation. Fasting serum Ca was significantly higher and PTH significantly lower in I-HC than in controls, whereas in fasting urine cAMP and phosphate were unchanged. There were only minor differences between fasting blood glucose levels and postprandial glucose tolerance of RCU patients and controls. However, serum insulin was significantly elevated in I-HC versus C, but serum C-peptide, plasma glucagon, and somatostatin levels were comparable in RCU and C. FFA were significantly lower in RCU than C. Postprandial phosphaturia and urinary saturation with Ca-phosphates were significantly higher in RCU versus C, whereas urinary cAMP, pH, and oxalate were similar. We conclude that: (1) in RCU patients some postabsorptive steps in glucose metabolism may be abnormal; (2) those with I-HC have enhanced postprandial Ca and phosphate excretion concomitantly with disordered insulin metabolism; and (3) RCU patients may suffer from a postprandial renal phosphate leak, which may make their urine more lithogenic.

Adult↗
PubMed1988

A sex cord stromal tumour in a woman with XO/XX/XXX-mosaicism.

We describe a postmenopausal woman with 45,XO/46,XX/47,XXX mosaicism who presented with a Sertoli-Leydig cell tumour and a past history of habitual abortion. The cytogenetic finding is discussed in relation to the etiology of the tumour and of the recurrent abortions.

Female↗
PubMed1988

Urinary pyrophosphate in patients with recurrent calcium urolithiasis and in healthy controls: a re-evaluation.

The excretion of inorganic pyrophosphate was studied in daily, fasting and postprandial urine specimens of normocalciuric and hypercalciuric patients with recurrent renal calcium stone disease (40 men and 40 women), and healthy controls (20 men and 20 women). Both populations were subdivided into younger (20 to 40 years old) and older (more than 40 years old) individuals. In general, there was a tendency towards higher urinary pyrophosphate excretion with increasing age (both sexes and all groups studied), and lower excretion in women than in men. The urinary pyrophosphate excretion rate was unchanged in daily and fasting urine specimens of the younger male normocalciuric and idiopathic hypercalciuric stone patients, whereas in the daily and postprandial urine of younger women the median excretion rate was reduced (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 3 versus 1 mumol., p less than 0.05). In contrast, in older men urinary pyrophosphate was reduced in daily specimens (controls versus normocalciuric plus idiopathic hypercalciuric subjects, 55 versus 33 mumol., p less than 0.05) but it was unchanged in fasting urine specimens. In older women no change was detectable in any of the 3 urine portions. Factorization of urinary pyrophosphate for the associated urinary creatinine did not alter these results substantially, and the presence of renal stones did not modify pyrophosphate excretion significantly. Urinary pyrophosphate was correlated significantly with urinary volume, citrate and phosphorus. We conclude that only subclassification of stone patients with respect to sex, age and type of calciuria, and consideration of additional urine portions besides the daily urine may help to uncover states of urinary pyrophosphate deficit. On the basis of the data, we recommend that clinically relevant studies on inhibitory effects of urinary pyrophosphate on the nucleation and growth of crystals and stones should be done preferentially in urine portions with a proved pyrophosphate deficit.

Adult↗