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Biomedical subjects

N H Herzberg

Publications and source records attributed to N H Herzberg.

11 recordsLinked to original sources
PubMed2000

Apoptosis of infiltrating cells in experimental autoimmune uveoretinitis.

OBJECTIVE: To investigate the cellular phenotype and apoptosis of infiltrating cells involved in experimental autoimmune uveoretinitis (EAU). METHODS: Immunohistochemical staining and in situ apoptosis staining were performed using monoclonal antibodies to monocytes and macrophages (ED1), major histocompatibility complex (MHC) class-II antigen (OX6), T lymphocytes (R73) and TACS 1 Klenow kit on both ocular sections and wholemounts from Lewis rats after immunization with interphotoreceptor retinoid-binding protein (IRBP). RESULTS: EAU was induced in 12 of 16 Lewis rats with a mean clinical inflammation score of 1.29 +/- 0.7. Influx of monocytes, lymphocytes and MHC class II-positive cells into the uvea and retina was noted after immunization with IRBP. Apoptosis of infiltrating cells was observed in the uvea and retina, and more apoptotic cells were present in the iris and ciliary body compared with those in the choroid and retina. CONCLUSION: Apoptosis of infiltrating cells occurs at the early stage of EAU, which may greatly contribute to the rapid regression of the inflammation induced by IRBP.

Animals↗
PubMed1994

Cultured human muscle cells and respiratory chain deficiencies.

Cultured muscle cells are useful in the study of respiratory chain disorders. Muscle tissue is affected in most cases and muscle biopsies are often taken for diagnostic purposes. Small samples of the biopsies can provide large numbers of muscle cells. In contrast with most other cell types, the muscle cells can differentiate in culture. Upon differentiation, multinuclear myotubes are formed by fusion of myoblasts and muscle-specific proteins are synthesized in the myotubes. Muscle cells can be used for diagnostic purposes, e.g. by measurement of the lactate and pyruvate synthesis, although with the limitation that not each form of respiratory chain deficiency may be expressed in culture. Muscle cells have been studied to obtain insight into mitochondrial DNA disorders, e.g. by investigation of cells after exposure to inhibitors of expression of mitochondrial DNA. Furthermore, cultured muscle cells have been studied to explore the potential of new therapeutic possibilities such as myoblast transfer and gene therapy.

Cells, Cultured↗
PubMed1993

Differentiation and proliferation of respiration-deficient human myoblasts.

Replication and transcription of mitochondrial DNA were impaired in dividing human myoblasts exposed to ethidium bromide. MtDNA content decreased linearly per cell division and mitochondrial transcript levels declined rapidly, resulting in respiration-deficiency of the myoblasts. Despite the absence of functional mitochondria the cells remained able to proliferate when grown under specific culture conditions. However, the formation of myotubes was severely impaired in respiration-deficient myoblasts. We conclude that differentiation of myoblasts into myotubes is more dependent on mitochondrial function than proliferation of myoblasts.

Adenosine Triphosphate↗
PubMed1993

Kearns-Sayre syndrome with a phenocopy of choroideremia instead of pigmentary retinopathy.

Mitochondrial DNA (mtDNA) was deleted in a patient with Kearns-Sayre syndrome (KSS) presenting with a choroideremia-like fundus picture instead of pigmentary retinopathy. No evidence for X-linked choroideremia was present, and because of the strong association between KSS and deleted mtDNA, we suggest that choroideremia is a phenocopy and can be part of KSS.

Adult↗
PubMed1993

Mitochondria in cultured human muscle cells depleted of mitochondrial DNA.

Cultured human muscle cells were depleted of mitochondrial DNA (mtDNA) by prolonged treatment with ethidium bromide (EB). In these respiration-deficient muscle cells neither cytochrome c oxidase activity nor mtDNA were detectable. However, mitochondrial matrix enzymes remained present and were localized in mitochondria-like organelles, as shown by subcellular fractionation. Metabolic labeling showed synthesis of cytochrome c oxidase subunits coded by nuclear DNA (nDNA). These results indicate that depletion of mtDNA in cultured human myoblasts does not inhibit expression of nDNA-coded mitochondrial proteins. The characteristic thread-like pattern of mitochondria was lost in mtDNA-depleted myoblasts, as shown by immunofluorescence with antibodies against cytochrome c oxidase and the F1 part of the mitochondrial ATP synthase (F1-ATPase) and by fluorescence of the carbocyanine dye, 3,3'-dipentyloxacarbocyanine iodide (DiOC5(3)). The organelles visualized by these methods were round and swollen and had a localization different from lysosomes as shown by double-labeling with mitochondrial and lysosomal antibodies. These results indicate that not only synthesis, but also import of mitochondrial proteins into mitochondria-like organelles remains possible in respiration-deficient cells.

Cell Nucleus↗
PubMed1992

Steady-state transcript levels of cytochrome c oxidase genes during human myogenesis indicate subunit switching of subunit VIa and co-expression of subunit VIIa isoforms.

Steady-state levels of the mitochondrial rRNAs, of mRNAs for mitochondrially and nuclear-encoded subunits of cytochrome c oxidase and for the beta subunit of ATP synthase were assessed by Northern blot hybridizations during the in vitro differentiation of human myoblasts. Transcript levels of the so-called liver-type form of subunit VIa of cytochrome c oxidase diminished during the course of differentiation, while transcription of the so-called heart-type form was induced. Transcripts for the liver-type form and for the heart-type form of subunit VIIa of cytochrome c oxidase were detected in all myogenic cultures; the levels of the heart-type form progressively increased during the course of differentiation. The levels of the other transcripts studied did not change substantially. The results suggest subunit switching of subunit VIa and co-expression of subunit VIIa isoforms during myogenesis. The differential changes in mRNA levels of the heart-type subunits VIa and VIIa and the differential changes in mRNA levels of the liver-type subunits VIa and VIIa demonstrate that different transcriptional regulation mechanisms are present for both heart-type genes as well as for both liver-type genes.

Adenosine Triphosphatases↗
PubMed1992

Major growth reduction and minor decrease in mitochondrial enzyme activity in cultured human muscle cells after exposure to zidovudine.

Zidovudine-induced mitochondrial myopathy in AIDS patients reported recently might be due to inhibition of mitochondrial DNA polymerase gamma. We investigated the effect of zidovudine on proliferation, differentiation, activity of mitochondrial- and nuclear-encoded enzymes, and mitochondrial DNA (mtDNA), in cultured human muscle cells. Marked inhibition of cell proliferation was found, even in the presence of low (10 mumol/L) zidovudine concentrations. Enzyme activity of the nuclear-encoded mitochondrial citrate synthase was not affected, and the partially mitochondrial-encoded cytochrome c oxidase was not decreased, except only after exposure to high concentrations (5 mmol/L) zidovudine. No decrease of mtDNA content and no mtDNA deletions were found in zidovudine-exposed muscle cells. We propose that the effect of zidovudine on muscle, seen in zidovudine-treated AIDS patients, results mainly from decrease in proliferation of muscle cells rather than inhibition of mtDNA replication.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Muscle cell cultures in Menkes' disease: copper accumulation in myotubes.

We present 64Cu uptake studies in cultured muscle cells from a one-year-old patient with Menkes' disease. The cultured muscle cells from the patient showed a five-fold higher 64Cu uptake than control muscle cells. Copper uptake in muscle cells was of the same magnitude as that found in fibroblasts from the patient and also from other Menkes' patients. The copper content of a muscle biopsy from the patient was twice that of a control biopsy. The enhanced uptake is probably copper specific, since zinc uptake was unaltered in both muscle cells and fibroblasts from the patient. Cytochrome c oxidase in the muscle of the patient was reduced to one-third of the value for controls, which is in agreement with the hypothesis that in Menkes' disease copper accumulates in a biologically non-active form. However, in cultured muscle cells and fibroblasts from the patient the cytochrome c oxidase activity was in the normal range, probably because of the relatively large amount of copper already available in the culture medium.

Brain Diseases, Metabolic↗
PubMed1990

Metallothionein in Menkes' disease: induction in cultured muscle cells.

Menkes' disease is an inherited disturbance of copper metabolism. Addition of copper to the medium of cultured fibroblasts and lymphoblasts from patients with Menkes' disease results in an increased induction of metallothionein. We investigated the metallothionein induction in response to copper and zinc in muscle cells (myoblasts and myotubes). Metallothionein synthesis was analyzed by gel electrophoresis of labeled proteins and metallothionein synthesis in muscle cells was compared with the synthesis in fibroblasts. The induction by copper was higher both in muscle cells and in fibroblasts from the Menkes' patient compared to the control cells. Hybrid myotubes obtained by fusion of control myoblasts and Menkes' myoblasts render a system in which complementation can be studied. Metallothionein synthesis in hybrid myotubes occurred at a level intermediate between the synthesis in Menkes' and control myotubes. The abnormal accumulation of copper-induced metallothionein was only partially corrected by fusion with normal cells. Metallothionein induction by zinc was similar in Menkes' and control fibroblasts. Combination of copper and zinc yielded no differences in additional metallothionein synthesis for Menkes' cells and control fibroblasts. Therefore, metallothionein induction in Menkes' disease can primarily be accounted for by copper rather than by zinc.

Cell Fusion↗
PubMed1989

Testosterone treatment restores reduced vasopressin-binding sites in the kidney of the ageing rat.

Young, middle-aged and aged rats received s.c. testosterone implants for 50-52 days in order to investigate whether supplementation of testosterone in aged rats could normalize the reported reduction of kidney arginine vasopressin (AVP)-binding sites and increase the plasma concentration of AVP. Receptor number, which was measured by means of a membrane-binding assay with [3H]AVP as ligand, was below the detection level in the untreated aged rat. Following testosterone treatment, no effects were seen in the youngest groups, but in the aged group AVP receptors became clearly detectable, albeit with a lower affinity. A remarkable observation was the increase in affinity for renal AVP binding in the middle-aged compared with the young rat. Plasma levels of AVP in control aged rats tended to be higher. Such a tendency was completely absent in the testosterone-treated aged rats. Possible mechanisms underlying the restoration of reduced AVP-binding sites in the kidney of the aged rat by testosterone treatment are discussed.

Aging↗