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Biomedical subjects

A Kleinschmidt

Publications and source records attributed to A Kleinschmidt.

At least 19 recordsLinked to original sources
PubMed1992

Growth inhibition of HIV-1-infected cells and membrane alterations induced by phosphatidylcholine.

Cultured T-lymphoma cell lines H9 and KE37-1 permanently infected with human immunodeficiency virus (HIV-1, strain HTLV-III B) were exposed to phosphatidylcholine (PC) and a PC-containing formulation "Essentiale" (PC-E). PC and PC-E, but not triglyceride, were found to inhibit growth of virus-infected cells. Additionally, the membrane lipid composition of infected and uninfected H9 cells was investigated upon exposure to PC. The HIV-1-infected cells showed a 25% increase in membrane triglyceride content and a 15% increase in membrane phospholipid saturated fatty acids. In the presence of PC, there is a further increase in triglyceride content up to 180% compared with uninfected control cells, suggesting a possible cause for the selective growth inhibition of HIV-1-infected cells by PC. The PC-E dose range effective in vitro for inhibition of HIV-1-infected cell growth falls within the range that can be reached in vivo. Formulations containing PC are well tolerated by humans and might be applicable at an early stage of HIV-1 infection to reduce the number of virus-producing cells.

Cell Division↗
PubMed1992

Biological markers associated with prolonged survival in African children maternally infected by the human immunodeficiency virus type 1.

Sixteen children over the age of 5 years (Group 1) have been identified out of 537 children infected by human immunodeficiency virus and born to HIV-infected mothers, in Kigali, Rwanda. They were followed up for 2 years and compared with 16 younger AIDS patients (Group 2) and with 16 age- and gender-matched HIV-1 seronegative children (Group 3). Fourteen Group 1 subjects had anti-HIV-1 IgM which persisted during the entire study period, in 11 cases directed to HIV-1 envelope proteins. In vitro, immortalization of B lymphocytes by the Epstein-Barr virus confirmed a high production of IgM to envelope proteins. All these patients had anti-p 17 IgG which was not observed in 7 patients from Group 2. All 16 children mounted significant titers of neutralizing antibodies to HTLV-IIIB, and, in 8 patients tested, against two other HIV-1 strains, RII and MN. HIV-1-specific major histocompatibility complex (MHC)-restricted cytotoxic T cells were demonstrated in 3 of 5 of the subgroup who were tested. Prolonged survival over 5 years in children with maternally acquired HIV-1 infection is associated with a high titer of neutralizing antibodies, a persistent production of IGM to HIV-1 envelope proteins and of IgG to p 17.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

Sex but no hand difference in the isthmus of the corpus callosum.

We performed high-resolution magnetic resonance morphometry of the total midsagittal area and seven midsagittal subareas of the corpus callosum in healthy young adult dextrals and sinistrals (N = 52). There was no influence of handedness on these anatomic measurements. However, an effect of sex emerged, with women (N = 26) having a larger proportional isthmus segment of the callosum. This may reflect a sex-specific difference in the interhemispheric connectivity and functional organization of the temporoparietal association cortex.

Adult↗
PubMed1992

Infection of human brain cells by HIV-1: restricted virus production in chronically infected human glial cell lines.

OBJECTIVE: To study expression of HIV-1 in human glial cell lines. DESIGN: Chronically HIV-1-infected glial cell lines were established to evade potential artefacts resulting from unphysiological viral entry (i.e., transfection). These cell lines were used to study viral expression and regulation. METHODS: Chronically infected glial cell lines were established by terminal dilution cloning of human glioma cells exposed to HIV-1. Virus production and expression were assayed by measuring reverse transcriptase activity, p24-antigen levels and syncytia-inducing capacity in C8166 target cells (extracellular), or by indirect immunoperoxidase staining, immunoblot analysis, and p24- and Nef-antigen-capture enzyme-linked immunosorbent assays (intracellular). HIV-long terminal repeat (LTR)-dependent expression of the chloramphenicol acetyltransferase reporter gene was determined in transient transfection assays. RESULTS: Culture supernatant from chronically HIV-1-infected glial cells contained only low levels of virus compared with chronically HIV-infected fibroblasts and T-lymphoma cells. Detailed study of HIV-antigen expression in representative glial cell line TH4-7-5 indicated the presence of all major structural proteins, albeit at low levels, and of Vif, Tat, Rev and Nef. Intracellular levels of Nef exceeded p24-antigen levels by approximately 10-fold. Virus was recovered from TH4-7-5 cells by cocultivation with blood-derived target cells, indicating that low-level virus production is not due to defective provirus. Prominent negative regulatory element (NRE)-mediated suppression of exogenous HIV-LTR activity was observed in TH4-7-5 cells and was unequalled by chronically HIV-producing fibroblast cells or by uninfected fibroblast and glial cells. CONCLUSIONS: Our results suggest that restricted virus production by chronically infected glial cells involves LTR-mediated regulation of virus expression.

Base Sequence↗
PubMed1991

Serological markers as prognostic criteria for the course of HIV infection.

576 serum samples from 139 HIV infected patients were analyzed for the presence of HIV antigens, as well as anti-core, anti-env and neutralizing antibodies. The results were correlated with the clinical and immunological stages of the patients. While almost all sera were positive for anti-env antibodies, only two thirds of the same sera had antibodies to core proteins. The average antibody titres, particularly of anti-core antibodies, decreased with the onset of clinical symptoms. The presence of p24 antigen could be demonstrated in only 16% of the sera. A positive reaction for core antigen seemed to be correlated with the absence of anti-core antibodies. Env specific neutralizing antibodies were found to be present in all of the sera analyzed in the LC5-test with a maximum neutralizing capacity observed in sera from WR 4 patients. A useful serological marker must fulfil two criteria, namely positive reactivity in the majority of sera examined and a broad range of antibody titres. None of the above described parameters meet these demands. Here we describe the search for new antibody markers, for example antibodies directed against HIV regulatory proteins.

AIDS-Related Complex↗
PubMed1991

Characterization of N-myristoyl transferase inhibitors and their effect on HIV release.

Acylation of virus proteins is an important covalent modification which has been shown, in many cases, to be necessary for their normal function. Furthermore, it has been shown that cerulenin, an inhibitor of this process, inhibits formation of vesicular stomatitis virus and Rous sarcoma virus in infected cultures, as well as acylation of HIV proteins. However, in agreement with earlier reports, we found that the acylating enzyme, N-myristoyl transferase, was unaffected by cerulenin which did, however, inhibit protein synthesis, thereby making interpretation of its effects difficult. Analogues of myristic acid were found to inhibit acylation in intact cells without toxic effects on protein synthesis or mitochondrial function. Myristic acid analogues were also shown by an in vitro assay to act directly on the acylating activity (N-myristoyl transferase). Furthermore, myristic acid analogues were found to inhibit HIV release from HIV-infected cells and glucosamine, which has recently been shown to be a non-competitive inhibitor of N-myristoyl-transferase, also inhibited HIV release.

Acylation↗
PubMed1990

Infection of human fibroblasts and osteoblast-like cells with HIV-1.

Primary human skin- and lung-derived fibroblast cell cultures and continuous human osteoblast-like and fibroblast-like cell lines were infected with different strains of HIV-1. Infection was measured at the single-cell level using the immunoperoxidase staining method to detect viral proteins. No cytopathic effects were observed in HIV-1-infected cell cultures. One continuous cell line (LC5), derived from embryonic lung, was readily infectable with HIV-1 and showed continuous production of infectious virus. Infection of LC5 cells could be blocked with anti-CD4 monoclonal antibodies. These findings indicate that fibroblasts of skin and lung, and osteogenic cells may be considered as potential target cells for HIV-1, thereby possibly contributing to the establishment of local HIV reservoirs.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Disruption of experience-dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist.

To assess the possibility that NMDA receptors play a special role in visual cortical plasticity, the selective antagonist 2-amino-5-phosphonovaleric acid (APV) was continuously infused into the striate cortex of kittens as the visual environment was manipulated during the critical period. The cortex was studied using single-unit recording from sites between 3 and 6 mm from the infusion cannulae. One week of D,L-APV infusion coincident with monocular deprivation or "reverse suture" produced a concentration-dependent increase in the percentage of neurons that (1) lacked normal orientation selectivity and (2) were responsive to stimulation of the deprived eye. These effects outlasted the presence of the drug in the tissue. APV treatment also prevented the acquisition of selectivity and visual responsiveness that normally results from monocular visual experience after dark-rearing. Lasting effects of chronic APV infusion were not observed in adult striate cortex. The effects of APV on kitten striate cortex depended on the presence of the D stereoisomer as infusion of L-APV was without effect. Estimates of extracellular concentration using 3H-APV indicated that significant effects could be obtained with concentrations as low as 20 microM D,L-APV. Recordings from units during infusion indicated that visual responses were reduced by APV. Nonetheless, a normal percentage of visually responsive neurons was found at sites greater than or equal to 3 mm from the infusion cannula. There was no evidence that chronic APV infusion affected the sampling frequency of recorded neurons or disrupted cytoarchitecture at the sites further than 3 mm from the infusion cannula. Taken together, the data indicate that the effects of APV on kitten striate cortex are likely due specifically to the blockade of NMDA receptors. These data are considered in relation to several hypotheses concerning the role of NMDA receptors in the experience-dependent development of striate cortex.

2-Amino-5-phosphonovalerate↗
PubMed1988

Experience-dependent modifications of kitten striate cortex are not prevented by thalamic lesions that include the intralaminar nuclei.

It has been shown previously that surgical lesions of the antero-medial thalamus interfere with ocular dominance modifications that normally result from monocular deprivation in young kittens (Singer 1982). The aim of the present study was to determine whether this effect was due specifically to the destruction of the visual cortical projections of the anterior intralaminar nuclei. We report here that large excitotoxin lesions of the anterior dorsal thalamus have no effect on the cortical response to monocular deprivation. These data indicate that the intralaminar projection is not essential for ocular dominance plasticity.

Animals↗
PubMed1987

Blockade of "NMDA" receptors disrupts experience-dependent plasticity of kitten striate cortex.

Intracortical infusion of the "N-methyl-D-aspartate" (NMDA) receptor blocker D,L-2-amino-5-phosphonovaleric acid (APV) renders kitten striate cortex resistant to the effects of monocular deprivation. In addition, 1 week of continuous APV treatment (50 nanomoles per hour) produces a striking loss of orientation selectivity in area 17. These data support the hypothesis that crucial variables for the expression of activity-dependent synaptic modifications are a critical level of postsynaptic activation and calcium entry through ion channels linked to NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1979

Temperature-sensitive mutants of Physarum polycephalum: viability, growth, and nuclear replication.

Using a selfing strain of Physarum polycephalum that forms haploid plasmodia, we have isolated temperature-sensitive growth mutants in two ways. The negative selectant, netropsin, was used to enrich for temperature-sensitive mutants among a population of mutagenized amoebae, and, separately, a nonselective screening method was used to isolate plasmodial temperature-sensitive mutants among clonal plasmodia derived from mutagenized amoebae. Complementation in heterokaryons was used to sort the mutants into nine functional groups. When transferred to the restrictive temperature, two mutants immediately lysed, whereas the remainder slowed or stopped growing. Of the two lytic mutants, one affected both amoebae and plasmodia, and the other affected plasmodia alone. The growth-defective mutants were examined for protein and deoxyribonucleic acid synthesis and for aberrations in mitotic behavior. One mutant may be defective in both protein and deoxyribonucleic acid synthesis, and another only in deoxyribonucleic acid synthesis. The latter shows a striking reduction in the frequency of postmitotic reconstruction nuclei at the restrictive temperature. We believe that this mutant, MA67, is affected in a step in the nuclear replication cycle occurring late in G2. Execution of this step is necessary for both mitosis and chromosome replication.

Cell Nucleus↗
PubMed1978

[The effect of benzbromarone on fasting-hyperuricemia as a model (author's transl)].

The effect of daily therapeutic doses of 100 mg benzbromarone (Normurat) and 2.0 g probenecid on the purine metabolism of 40 test subjects was investigated. Fasting-hyperuricemia was used as the model and particular attention paid to the mechanisms of renal elimination. Urate concentration remains under the solubility threshold when benzbromarone is administered, in contrast to medication with probenecid. The significantly greater hypouricemic effect of benzbromarone correlates with a significant rise in the excretion and clearance of uric acid in comparison to probenecid, accompanied by a stronger depression of tubular reabsorption. Serum levels, clearances and reabsorption rates demonstrate the prolonged effect of the benzofurane derivative Normurat even during strict fasting. Supplementary allantoin and urea determinations gave no indication of increased enterobacterial uricolysis. Normurat was well tolerated, side effects were not noted.

Adolescent↗
PubMed1978

[The uricosuric effect of benzbromaron and probenecid under fasting conditions (author's transl)].

As we could demonstrate in a group of 39 obese subjects submitted to a 15-days period of absolute fasting, the developing hyperuricemia coincides with a decrease of uric acid clearance following an increase of the reabsorbed amount of filtered uric acid. After daily application of 2 g probenecid a marked uricosuric effect was detectable only during the first 3 days, while in the following time this effect was perceptible only impaired. As a reason for the diminution of efficacy the fasting-dependent urinary acidosis is discussed, which leads to low tubular concentration of the pharmacon by non ionic diffusion. In a dosage of 100 and 300 mg/day benzbromaron proved to be a much more potent uricosuricum. Additionally, related to the increase of dose the unproportional strong fall of serum uric acid levels, which stood in contrast to higher rations of uric acid excretion under a lower dose and which exceeded the dose-depending increase of uric acid clearance, indicated an additional extrarenal site of action. The depression of PAH-excretion after application of 2 g/day probenecid, which comes about the competitive inhibition, did not occur under 100 mg/day benzbromaron. This difference signifies, that benzbromaron does not develop its uricosuric effect by influencing the tubular transport system, which is specific for PAH and probenecid.

Benzbromarone↗