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Biomedical subjects

J Gehrmann

Publications and source records attributed to J Gehrmann.

At least 91 records · Page 5Linked to original sources
PubMed1989

Biochemical and developmental features of experimental phenylketonuria induced by L-ethionine in suckling rats.

Suckling rats were injected subcutaneously with doses of L-ethionine (0.1 mumole/g body wt) at intervals of 12 hr. In the latter group, phenylalanine hydroxylase was effectively inhibited in vivo resulting in hyperphenylalaninemia and phenylketonuria. Due to the well-known sex-specific differences in L-ethionine metabolism female rats were much more affected by chronic administration of L-ethionine. The underlying mechanism of enzyme inhibition by ethionine could be disturbed protein synthesis and impaired protein phosphorylation, which was suggested by pronounced decreases in ATP content in liver. In the high dosage group depletions mainly of the branched-chain amino acids and lysine occurred in serum and brain, whereas the concentrations of methionine and tryptophan were increased. Tyrosine tended to be decreased in the course of hyperphenylalaninemia. Hyperphenylalaninemia and other resulting amino acid imbalances obviously impaired brain development during the early postnatal period. Concomitantly with reductions in protein concentrations, the activity of cathepsin D, a major intralysosomal acid proteinase, was increased in brain, suggesting also higher protein catabolism in brain. Side effects of this treatment, however, were higher mortality, loss of body weight, and a general impression of delayed development, resembling a state of undernutrition to some extent. These obvious side effects of ethionine limit the usefulness of ethionine as a suitable model for classic phenylketonuria in suckling rats.

Adenosine Triphosphate↗
PubMed1986

Induction of hyperphenylalaninemia in mice by ethionine and phenylalanine.

Female NMRI mice were fed diets containing l-ethionine (0.1 and 0.3% w/w) and phenylalanine (3% w/w), as well as respective control diets. Ethionine, the S-ethylated analog of methionine, was shown to inhibit phenylalanine hydroxylase in vivo, whereby in vitro kinetics remained unaffected. Treatment with ethionine resulted in fatty liver, reduced ATP content of liver, and alterations in serum amino acid concentrations. In the high dosage ethionine group, for instance, concentrations of Ala, Gly, Ser, Met, and Phe were increased whereas concentrations of Lys, Asp, and Pro were decreased. Applying ethionine together with phenylalanine resulted in hyperphenylalaninemia and phenylketonuria. Feeding phenylalanine alone also led to decreased activity of phenylalanine hydroxylase and increased concentration of Phe in serum. Ethionine only had a minimal effect on body weight gain; however, the hyperphenylalaninemic condition induced by application of the high dosage of ethionine and phenylalanine induced severe loss of body weight. A disturbed protein synthesis and protein phosphorylation might be the underlying mechanism of ethionine-induced suppression of phenylalanine hydroxylase.

Adenosine Triphosphate↗
PubMedDate not supplied

Electrophysiological characterization of murine myocardial ischemia and infarction.

BACKGROUND: Genetically altered mice will provide important insights into a wide variety of processes in cardiovascular physiology underlying myocardial infarction (MI). Comprehensive and accurate analyses of cardiac function in murine models require implementation of the most appropriate techniques and experimental protocols. OBJECTIVE: In this study we present in vivo, whole-animal techniques and experimental protocols for detailed electrophysiological characterization in a mouse model of myocardial ischemia and infarction. METHODS: FVB mice underwent open-chest surgery for ligation of the left anterior descending coronary artery or sham-operation. By means of echocardiographic imaging, electrocardiography, intracardiac electrophysiology study, and conscious telemetric ECG recording for heart rate variability (HRV) analysis, we evaluated ischemic and post-infarct cardiovascular morphology and function in mice. RESULTS: Coronary artery ligation resulted in antero-apical infarction of the left ventricular wall. MI mice showed decreased cardiac function by echocardiography, infarct-typical pattern on ECG, and increased arrhythmia vulnerability during electrophysiological study. Electrophysiological properties were determined comprehensively, but were not altered significantly as a consequence of MI. Autonomic nervous system function, measured by indices of HRV, did not appear altered in mice during ischemia or infarction. CONCLUSIONS: Cardiac conduction, refractoriness, and heart rate variability appear to remain preserved in a murine model of myocardial ischemia and infarction. Myocardial infarction may increase vulnerability to inducible ventricular tachycardia and atrial fibrillation, similarly to EPS findings in humans. These data may be of value as a reference for comparison with mutant murine models necessitating ischemia or scar to elicit an identifiable phenotype. The limitations of directly extrapolating murine cardiac electrophysiology data to conditions in humans need to be considered.

Animals↗
PubMedDate not supplied

Microglia in the immune surveillance of the brain: human microglia constitutively express HLA-DR molecules.

The degree of MHC class II expression in histologically normal human brain biopsy or autopsy tissue is still controversial. According to the generally held view MHC class II expression is rather low in the normal brain with the exception of the white matter. In the present study, HLA-DR expression was examined immunocytochemically in different brain areas obtained from three autopsy cases with short post-mortem times (i.e. 6 h). Based on standard histological evaluation, the brain areas studied appeared as histologically normal tissue. In all brain areas there was a strong constitutive HLA-DR expression on ramified microglia. The number of HLA-DR-immunoreactive microglia was strongest in the white matter (the corpus callosum and the capsula interna for example). The border zone between white matter and grey matter, however, revealed a sharp contrast between a high density of HLA-DR-immunoreactive microglia in the white matter and a rather low number in the grey matter. In the grey matter, HLA-DR-immunoreactive microglia were much less frequent than in the white matter and more pronounced on perivascular cells. The staining and distribution pattern of HLA-DR-immunoreactive microglia was confirmed by immunocytochemistry with a panel of different anti-HLA-DR monoclonal antibodies as well as by quantitative analysis of the immunostaining. Unlike the HLA-DR immunoreactivity, HLA-ABC immunoreactivity (detecting MHC class I antigens) was confined to endothelia and not observed on microglia. In the choroid plexus stromal macrophages expressed both class I and II antigens (i.e. at a location which could provide the peripheral immune system access to CNS antigens). Constitutive HLA-DR expression by microglia qualifies them as the main resident antigen-presenting cell of the brain. The pronounced overall HLA-DR expression by resting microglia questions a central dogma of the brain as an immune-privileged site and further points to the key role of the microglia in brain immune surveillance.

Adult↗
PubMedDate not supplied

Microglia: a sensor to threats in the nervous system?

The parenchymal microglia are now believed to settle the CNS antenatally, being derived from a bone marrow precursor cell. Based on developmental and pathophysiological studies, at least four different types of parenchymal microglia can be distinguished: (i) the amoeboid microglia which are mainly found perinatally in white matter areas, such as the corpus callosum, i.e. the so-called "fountains of microglia", (ii) the ramified, resting microglia in the adult CNS, (iii) the activated, non-phagocytic microglia found in areas of secondary reaction due to nerve transection and (iv) the phagocytic microglia, found in areas of trauma, infection or neuronal necrosis. In addition, there are perivascular cells enclosed in the basal lamina which have a high turnover with a bone marrow precursor pool. While the function of resting microglia is still largely unknown, it is clear from observations in neuropathology that microglia are among the first cell types in the brain to respond to injuries. Their reaction pattern to injury has been termed a graded response, since the transformation of resting cells into phagocytes is under strict control in vivo. Microglial activation is a key cellular response in many infectious, inflammatory, traumatic, neoplastic, ischaemic and degenerative conditions in the CNS. In HIV encephalitis, the microglial involvement is striking, and approximately 25% of microglia contain viral DNA or RNA. Based on natural homing mechanisms with bone marrow precursor cells, HIV-infected monocytes/macrophages may home at an early stage to the CNS perivascular space and eventually spread the infection to resident microglia in the CNS which may be difficult to reach by pharmacological intervention. Further understanding of the mechanisms regulating microglial proliferation and activation in vivo may help to develop therapies targeting the potentially harmful microglial response in the injured CNS.

AIDS Dementia Complex↗
PubMedDate not supplied

[A rare combination of partial trisomy 9 with pulmonary atresia].

We report of an previously unpublished combination of partial trisomy 9 and a membranous pulmonary atresia with a large conotruncal ventricular septal defect. The dystrophic female, term newborn presented after delivery with microcephaly, prominent nose and several other facial and skeletal deformities. The echocardiography and angiography showed a membranous pulmonary atresia with ventricular septal defect. Chromosomal analysis revealed a partial trisomy of the short arm with parts of the long arm of chromosome 9 and a small part of the long arm of chromosome 4. A surgical repair of the heart defect was not performed by the known high risk of severe mental retardation of partial trisomy 9. The child died at the age of six months.

Abnormalities, Multiple↗
PubMedDate not supplied

On the role of branched-chain amino acids in protein turnover of skeletal muscle. Studies in vivo with L-norleucine.

The effect of L-norleucine, an isomer of leucine, on protein metabolism in vivo was studied in suckling rats. Rats were injected subcutaneously with various doses of L-norleucine (0.5 and 5.0 mumol/g body wt.) every 12 h from 3 to 15 days post partum. Protein concentration, amino acid concentrations, and incorporation of [3H]tyrosine into protein were analyzed in liver, muscles of thigh and small intestine. Amino acid concentrations and insulin levels in serum were also measured. At 5 days of age, norleucine induced an increase in protein concentration of skeletal muscle with an increased incorporation of [3H]tyrosine into protein indicating an accelerated protein synthesis. Changes in protein metabolism were paralleled by alterations in the amino acid pattern of this tissue. When protein concentration and protein synthesis were increased in skeletal muscle, protein concentration of small intestine was decreased, accompanied by elevated levels of amino acids in tissue. Protein synthesis of small intestine was not altered by the norleucine treatment. The results suggest a close interrelationship between skeletal muscle and small intestine with respect to protein turnover. The effects of norleucine were less pronounced at 10 and 15 days of age, which indicates a metabolic adaptation to the treatment. Alterations in amino acid concentrations of tissue due to changes in protein metabolism were not uniform but tissue-specific. Current concepts for explaining the effects of branched-chain amino acids (BCAA) on protein turnover in skeletal muscle are based on the assumption that the BCAA or leucine alone might become rate-limiting for protein synthesis in muscle under catabolic conditions. The amino acid analogue norleucine, however, cannot replace any of the BCAA in protein. Additionally, norleucine affected protein metabolism in highly anabolic organisms. Therefore, the present thoughts on this issue appear to be incomplete.

Aging↗