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Biomedical subjects

G Ulrich

Publications and source records attributed to G Ulrich.

At least 19 recordsLinked to original sources
PubMed1998

Chromogranin A induces a neurotoxic phenotype in brain microglial cells.

Chromogranin A (CGA) belongs to a multifunctional protein family widely distributed in secretory vesicles in neurons and neuroendocrine cells. Within the brain, CGA is localized in neurodegenerative areas associated with reactive microglia. By using cultured rodent microglia, we recently described that CGA induces an activated phenotype and the generation of nitric oxide. These findings led us to examine whether CGA might affect neuronal survival, expression of neurofilaments, and high affinity gamma-aminobutyric acid uptake in neurons cultured in the presence or absence of microglial cells. We found that CGA was unable to exert a direct toxic effect on neurons but provoked neuronal injury and degeneration in the presence of microglial cells. These effects were observed with natural and recombinant CGA and with a recombinant N-terminal fragment corresponding to residues 1-78. CGA stimulated microglial cells to secrete heat-stable diffusible neurotoxic agents. CGA also induced a marked accumulation of nitric oxide and tumor necrosis factor-alpha by microglia, but we could not establish a direct correlation between the levels of nitric oxide and tumor necrosis factor-alpha and the neuronal damage. The possibility that CGA represents an endogenous factor that triggers the microglial responses responsible for the pathogenesis of neuronal degeneration is discussed.

Animals↗
PubMed1997

[Use of flow cytometry for HLA B27 phenotyping: study of a HLA B7/HLA B27 double marker technique].

Among HLA-associated diseases, the strong association between HLA B27 and ankylosing spondylitis (AS) allows to perform HLA B27 typing for the diagnosis of this disease. The technique described: double immunostaining anti-HLA B7/HLA B27 on whole blood samples and analysis by flow cytometry is a rapid method for the detection of HLA B27 antigen. We have compared the results obtained with those of the TERASAKI microlymphocytotoxicity reference method on a population of 300 patients. The absence of false negative results indicates that this test is suitable for AS screening. The use of two monoclonal antibodies proves to be effective in eliminating cross reactions described with HLA B7 flow cytometric techniques using single monoclonal antibody. This technique allows to restrict the use of microlymphocy-totoxicity to patients presenting with both HLA B7 and B27 positive reactivities.

Antibodies, Monoclonal↗
PubMed1996

Elevated levels of complement components C5 and C9 and decreased antitrypsin activity in the serum of patients with X-linked vacuolated myopathy.

We have recently reported a French family presenting with an X-linked vacuolated myopathy. Here we show that levels of complement components C5 and C9 are elevated in the serum of these patients. Moreover, antitrypsin activity is decreased in the serum of the patients. Taken with the deposition of membrane attack complex encountered in muscle tissue, these results emphasize the role of complement in the pathogenesis of this rare muscular disorder.

Complement C5↗
PubMed1996

Chromogranin A triggers a phenotypic transformation and the generation of nitric oxide in brain microglial cells.

Chromogranin A is an ubiquitous 48,000 mol. wt secretory protein stored and released from many neuroendocrine cells and neurons. In human brain, chromogranin A is a common feature of regions that are known to be affected by various neurodegenerative pathologies such as Alzheimer's, Parkinson's and Pick's diseases. Brain degenerative areas are generally infiltrated by activated microglial cells, the resident macrophage cell population within the central nervous system. Here, we report that both recombinant human chromogranin A and chromogranin A purified from bovine chromaffin granules trigger drastic morphological changes in rat microglial cells maintained in culture. Microglial cells exposed to chromogranin A adopted a flattened amoeboid shape and, this change was associated with an accumulation of actin in the subplasmalemmal region, as observed by immunocytochemistry and confocal laser microscopy. In single microglial cells loaded with indo-1, chromogranin A elicited a rapid and transient increase in [Ca2+]i which preceded the reorganization of actin cytoskeleton. The activity of nitric oxide synthase was estimated by measuring the accumulation of nitrite in the culture medium. Both recombinant human chromogranin A and bovine chromogranin A triggered an important accumulation of nitrite comparable to that induced by lipopolysaccharide, a well-known activator of microglia. The effect of chromogranin A was dose dependent, inhibited by N omega-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, and by cycloheximide, an inhibitor of protein synthesis. These findings suggest that chromogranin A induces an activated phenotype of microglia, and thus may have a role in the pathogenesis of neuronal degeneration in the brain.

Actins↗
PubMed1995

[Health promotion and prevention as responsibilities of the established physician--status and current deficits].

General practitioners have been questioned by the Society of panel doctors of Bavaria about the status, deficiencies and the future focus of prevention in the medical office. The results of this questionnaire was compared to similar studies from Niedersachsen and Switzerland. From these results, conclusions should be drawn for initiatives of the medical self-administration to improve the preventive out-patient care. Written questionnaires with a semi-structured form for all of the 1067 general practitioners in the district Oberfranken of the Society of panel doctors of Bavaria. Response 33.7%. Descriptive analysis of the answers and development of a list of priorities of further education in preventive medicine. Comparison of the results with questionnaires in German language. Preventive care plays an important role in the medical practice. However, the status of prevention has currently a lower importance as it would be appropriate. This is caused by unsatisfactory honorary, lack of further education, and lack of time for an adequate consultation. It was recommended that the medical self-administration should offer more further education about preventive medicine. In all three cited studies, first of many topics, where there was a need for further education, was nutrition followed by withdrawing from smoking and protection from infections.

Ambulatory Care↗
PubMed1995

Immunocytochemical localization of protein kinases Yes and Src in amoeboid microglia in culture: association of Yes kinase with vimentin intermediate filaments.

Amoeboid microglia isolated from primary cultures of neonatal rat brain correspond to a transient form of activated microglia, a resident population of macrophage-like cells. In order to understand the molecular aspects of microglial activation, we have studied amoeboid microglia in primary culture for the presence of Yes and Src protein tyrosine kinases, two kinases which have been implicated in signal transduction process during monocyte/macrophage activation. Immunofluorescence with an antibody raised against the peptide from unique N-terminal domains of Yes and Src demonstrated that Yes and Src kinases are enriched in perinuclear areas of amoeboid microglia. In addition, the antibody to c-yes peptide had a cytoplasmic distribution which coincided with the distribution of vimentin-containing intermediate filaments. Preadsorption of anti-c-yes antibody with an excess of antigenic peptide inhibited anti-c-yes immunofluorescence, while vimentin immunofluorescence remained unchanged. Double immunofluorescence images analyzed with the two-dimensional intensity distribution program (2-D scattered histograms) on Zeiss confocal scanning laser microscope demonstrate the colocalization of c-yes with vimentin. The extent of colocalization was more prominent after exposure of intact cultured microglia to dibutyryl cyclic AMP (dBcAMP), or to phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) or to okadaic acid, an inhibitor of protein phosphatases. The findings suggest that vimentin might serve as molecular support for Yes kinase and, since previous studies have shown that vimentin in amoeboid microglia is one of the major protein substrates of serine/threonine protein kinases, this function could be regulated by phosphorylation.

Animals↗
PubMed1994

Bacterial endotoxin induces [Ca2+]i transients and changes the organization of actin in microglia.

We have employed amoeboid microglia purified from primary cultures of neonatal rat brain to examine the effect of bacterial lipopolysaccharide (LPS), a potent activator of immune cells, on intracellular calcium concentration ([Ca2+]i) in brain macrophages. In single brain macrophages loaded with indo 1, pulse administration of LPS elicited a rapid and transient increase in [Ca2+]i. From a total of 70 cells examined, all responded to LPS with a similar [Ca2+]i transient, indicating a good homogeneity of the cell population with regard to the LPS response. It was concluded that the rise of cytosolic [Ca2+]i originated from intracellular stores because the response to LPS occurred similarly in the presence or in the absence of extracellular Ca2+. A second administration of LPS to the same cells resulted in a second but reduced [Ca2+]i transient. In contrast to the first response to LPS, this second response was totally dependent on the presence of Ca2+ in the extracellular medium. The first response to LPS was strongly inhibited by ruthenium red and could be suppressed in a reversible manner by preincubating the cells with caffeine in the absence of Ca2+ in the extracellular medium. These results indicate that caffeine-sensitive intracellular Ca2+ stores may be the major source of Ca2+ in the response of brain macrophages to LPS. The possible release of Ca2+ from phosphatidylinositol(3,4,5)-trisphosphate (IP3)-sensitive stores in brain macrophages was also evaluated by stimulating cells with the IP3-mobilizing agonist histamine. Brain macrophages were heterogeneous with regard to the histamine response since histamine induced a [Ca2+]i rise in only 30% of cells examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMed1994

Acute vs. chronic EEG effects in maprotiline- and in clomipramine-treated depressive inpatients and the prediction of therapeutic outcome.

Patients treated with the norepinephrine uptake inhibitor maprotiline showed an opposite tendency between acute and chronic effect of EEG. Whereas the acute effect indicated a decrease upon EEG vigilance, the chronic effect indicated an increase. Under clomipramine which acts upon different transmitter systems in a complex, up to now not fully understood way, acute and chronic EEG effects could not be differentiated.

Adult↗
PubMed1994

Electroencephalographic response prediction of antipsychotic drug treatment in acutely ill patients and of long-term prophylactic treatment with lithium salts.

The use of the EEG as a pharmacotherapeutic response predictor is still hampered by the largely unsolved problem of extracting the relevant information from the recording in a theory-guided manner and by the likewise largely underestimated fact of pathobiological heterogeneity in diagnostically homogenous groups of patients. Instead of the usual group-statistical designs that rely solely on homogenous psychopathology, we advocate a strategy of single case studies, performed as comprehensive as possible and giving special attention to the baseline condition. It is only a certain number of such single case studies that afford an empirical data base for meaningfully applicating statistical procedures.

Acute Disease↗
PubMed1994

["Neuroadaptation" in long-term cannabis abuse. A clinical and electroencephalographic case study].

This report is about electroencephalographic changes in a twenty-eight year old patient with longterm heavy cannabis use. He was admitted to our hospital after he had developed a depressive-apathetic syndrome. Two days after the last cannabis-intake, the patient had recovered from initial psychopathology and his EEG was completely inconspicuous at this day. Some days later however the patient's behavior became increasingly impulsive and unstable, while his EEG showed a marked disturbed regulation of vigilance. In the following weeks his impulsiveness became less and his EEG returned to normal. We suggest that these alterations may reflect a discontinuation of the initial neuroadaption of the central nervous system to the drug.

Adult↗
PubMed1993

Differences in vimentin distribution in glial cells in culture revealed with an antibody against a phosphorylated epitope.

We have previously described that spatial and temporal changes in the organization of vimentin that are correlated with protein kinase C (PKC)-induced phosphorylation of vimentin can be detected with the mouse monoclonal antibody B3 in cultures of amoeboid microglia [Ciesielski-Treska et al. (1991) J. Neurosci. Res. 29, 362-378]. The antibodies were generated to native form of vimentin-containing filaments and antibody B3 reveals a restricted immunostaining of vimentin in glial cells from human, rat and mouse origin. In the present study we show the distribution of epitope B3 analyzed by immunofluorescence within defined populations of rat glial cells. Relatively high immunoreactivity was found in Type 1 astrocytes, Type 2 astrocytes and oligodendrocytes had low immunoreactivity. Although the results suggested that in Type 1 astrocytes the phosphorylated epitope is prominent, its phosphorylation was not found to be cell cycle-dependent, and appeared unrelated to the organizational changes of intermediate filaments associated with the morphological conversion of polygonal to stellate astrocytes. As expected, the immunofluorescence was increased by exposition of astrocyte cultures to an activator of PKC, confirming our previous conclusion that the immunoreactivity of the epitope B3 depends on PKC-mediated phosphorylation. In addition, the finding that the immunofluorescence of vimentin was more homogeneous in quiescent, serum-deprived astrocytes and also in astrocytes exposed to an inhibitor of protein synthesis, cycloheximide, may suggest that phosphorylation of the epitope B3 depends on a protein factor present in fetal calf serum. The immunofluorescence studies on cultures enriched in Type 2 astrocytes and in oligodendrocytes indicate that the epitope B3 is hypophosphorylated in glial cells of this lineage and becomes dephosphorylated after terminal differentiation of oligodendrocytes. These observations suggest that in Type 2 astrocytes and in oligodendrocytes the low level of phosphorylation of vimentin could be related to the down regulation in vimentin expression.

Animals↗
PubMed1992

Line bisecting as a predictor of personal optimism and desirability of risky behaviors.

Our goal was to test whether current hemisphere predominance is a predictor of scores on standardized measures of personal optimism and preference for risk. In two between-subject experiments, current hemisphere predominance was measured by the direction and extent of line bisecting errors. Pearson correlations and median splits of the line bisecting errors showed significantly greater personal optimism and preference for risk with left hemisphere predominance. These results support previous research in which manipulation of hemisphere predominance produced similar effects on personal optimism in normal individuals and on risk taking in lesioned and normal samples. We conclude that the association of optimism and risk with left hemisphere predominance can be observed in resting as well as in manipulated situations.

Adolescent↗
PubMed1992

[Is global equivalent to multifocal? The whole and its parts in psychiatry and neurology].

According to an influential trend within contemporary neurology, psychiatry should abandon terms like "organic brain syndrome" or "dementia", which are regarded as out-dated. Such terms which imply the questionable possibility of global disturbances of the psychic apparatus, should be replaced by a classification based on detailed neuropsychological analysis. The response of psychiatry to this challenge is essentially lacking. An examination of the reasons leads us to the methodological contradiction between categorical and global models. We consider that we here are not confronted by a decision between mutually exclusive alternatives but that the two models necessarily complement each other. From this it follows that only a biperspectivistic view is adequate to the matter under consideration. This is equally requisite both for psychiatry and neurology, though an accentuation of the one or the other perspective may be expedient for each individual syndrome.

Brain Damage, Chronic↗
PubMed1991

[Prognostic value of the study of the blood flow in the fetal median cerebral artery].

Medial cerebral artery blood flow velocity waveforms were examined by pulsed Doppler ultrasound between the 28th and 41st week of pregnancy. It has been found that the vessel showed an increased resistance at the beginning of the third trimester, which significantly decreased till term. In intrauterin hypoxia the diastolic component of the blood flow velocity waveform of medial cerebral artery becomes stronger, marking the centralisation of the circulation. By their opinion the examination of the blood flow in the medial cerebral artery would be an effective additional possibility of the other intrauterine diagnostic methods (both the positive and the negative predictive value were higher than 90%) for the notifying the post-partal condition of the fetus.

Blood Flow Velocity↗
PubMed1991

Protein kinase C-induced redistribution of the cytoskeleton and phosphorylation of vimentin in cultured brain macrophages.

The phorbol ester 12-O-tetradecanoyl-acetate (TPA) induced prominent and transient changes in the organization of the cytoskeleton in cultured amoeboid microglial cells including redistribution of actin toward the center of the cells and in the subplasmalemmal region, appearance of fine actin filaments, retraction of microtubules (MT), and rearrangement of intermediate filaments (IF) containing vimentin. The possible implication of protein kinase C (PKC) in mediating the effects of TPA was suggested by a parallel shift of PKC activity from the soluble to membrane fractions and phosphorylation of several microglial proteins. The rearrangement of IF closely correlated with increased vimentin phosphorylation, detected by pulse labeling of intact cells. Two monoclonal antivimentin antibodies, B3 and V9, showed different staining patterns. Immunoreactivity with the antibody B3 was more restricted and could be abolished by treatment of fixed, permeabilized cells with alkaline phosphatase, thus suggesting that the antibody reacts with a phosphorylated epitope. Using this antibody, rearrangement of IF involving vimentin phosphorylation was detected within 15 to 60 min of treatment with 50 nM TPA and consisted in the appearance of intense perinuclear fluorescent label. This perinuclear fluorescence persisted up to 24 hr after TPA removal and gradually diminished during the following 2 to 3 days. Immunochemical analysis of nonionic detergent-soluble and -insoluble extracts from untreated and TPA-treated cells revealed no differences in vimentin solubility suggesting that TPA induced vimentin phosphorylation does not result in notable vimentin filament disassembly. However the extent of vimentin degradation was more prominent in TPA-treated cultures indicating a higher sensitivity of vimentin to proteolytic degradation. The data show that PKC-mediated phosphorylation of vimentin results in precise spatial and temporal rearrangement of IF which are not associated with altered vimentin solubility, but possibly changes the mechanical properties and interactions of vimentin filaments.

Actins↗
PubMed1991

Phosphorylation of cellular proteins in response to treatment with Clostridium difficile toxin B and Clostridium sordellii toxin L.

Toxin B from Clostridium difficile induces typical morphological changes of cultured cells consisting of rounding up and arborization, which are associated with a dramatic disruption of microfilaments. In this study, we show that toxin L, a cytotoxin produced by bacterial strain Clostridium sordellii, has similar effects on cultured cells including the redistribution of F-actin and of the adhesion plaque protein vinculin. It has been assumed that the mechanisms involved in cytopathic effects of toxin B are related to the function of an unidentified component that regulates the organization of the actin cytoskeleton. We demonstrate that the treatment of cultured astrocytes with toxin B or toxin L alters the incorporation of inorganic phosphate into several proteins. Immunoblot analysis revealed that one of these proteins is tropomyosin. Since tropomyosin stabilizes microfilaments and inhibits the severing activity of gelsolin, the toxin-induced phosphorylation may counteract this inhibition resulting in severing of microfilaments and capping of short filaments. A decrease in the radioactivity associated with intermediate filament protein vimentin was also detected using a monoclonal antibody which specifically recognizes a phosphorylated epitope of vimentin. Since vimentin is an in vivo substrate for various protein kinases, these data are in favor of broad effects of these toxins. Direct measurement of protein kinase C in cells exposed to toxin B or to toxin L did not reveal a significant change in protein kinase C activity. Furthermore, treatments with toxins do not increase cAMP levels, suggesting that toxins do not activate protein kinase A. Although further studies are required to determine the primary target site for the clostridial cytotoxin B and L, our results show that they provoke the alteration in the phosphorylation of cellular proteins.

Actin Cytoskeleton↗
PubMed1990

[Two-dimensional ultrasonic examination of the fetal heart].

The methodology of the two-dimensional fetal echocardiography is described by the basic of the accepted international nomenclature. By their opinion it is necessary that on the 18-20th weeks of gestation the high risk pregnancies in aspect congenital heart disease examined by the well-trained specialists. The indication of fetal echocardiography are listed, too.

Echocardiography↗