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Biomedical subjects

H Olbrich

Publications and source records attributed to H Olbrich.

14 recordsLinked to original sources
PubMed1999

Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus.

The binding of CC chemokines to CC chemokine receptor 5 (CCR5) triggers cellular responses that, generally, are only transient in nature. To explore the potential role of G protein-coupled receptor kinases (GRKs) in the regulation of CCR5, we performed phosphorylation experiments in a rat basophilic leukemia cell line stably expressing CCR5. The ability of various CCR5 ligands to stimulate calcium mobilization in these cells correlated with their ability to induce receptor phosphorylation, desensitization, internalization, and GRK association with the receptor. Aminooxypentane-RANTES, a potent inhibitor of human immunodeficiency virus infection, has been proposed to act through enhanced CCR5 internalization and inhibition of receptor recycling. Aminooxypentane-RANTES profoundly induced CCR5 phosphorylation, but had no effect on CCR1. In permeabilized rat basophilic leukemia CCR5 cells, monoclonal antibodies with specificity for GRK2/3 inhibited RANTES-induced receptor phosphorylation. Consistent with a role for these kinases in CCR5 regulation, 1-2 x 10(5) copies of GRK2 or GRK3 were found to be expressed in peripheral blood leukocytes. Phosphoamino acid analysis revealed that RANTES-induced CCR5 phosphorylation selectively occurs on serine residues. Our findings with receptor mutants indicate that serine residues at positions 336, 337, 342, and 349 represent GRK phosphorylation sites on CCR5. This study demonstrates that chemokines differ in their ability to induce CCR5 phosphorylation and desensitization and provides a molecular mechanism for the agonist-induced attenuation of CCR5 signaling.

Animals↗
PubMed1999

Chemokine-induced phosphorylation of CC chemokine receptor 5 (CCR5).

The CC-chemokine receptor 5 (CCR5) mediates activation of T lymphocytes and macrophages by chemokines and is a major co-receptor for macrophage-tropic HIV-1 strains. Recently, it was shown that the natural CCR5 ligands RANTES, macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, and amino-terminal modifications of RANTES (Met-RANTES, AOP-RANTES) significantly differ in their abilities to induce sequestration of CCR5 from cellular surfaces. It was hypothesized that these findings may account for the observed differences between these molecules to inhibit HIV infectivity in vitro. Herein we review our work on early regulatory mechanisms that are initiated by ligand binding to CCR5 and that, conceptually, are involved in receptor endocytosis. A better understanding of these mechanisms may provide new therapeutic strategies to prevent HIV infection.

Animals↗
PubMed1997

Can negative self-schemes in depressives be altered through sleep deprivation?

This paper addresses the question whether negative cognitive style represents a state or trait variable of depressive patients. For this reason, it studies the influence of sleep deprivation on negative self-schemes of those patients. 10 patients suffering from DSM-III-R major depression were compared with 10 age- and sex-matched controls on a task for rating the self-descriptiveness of positive and negative adjectives as well as a subsequent word recognition task. Three sessions were involved: an initial session (baseline), the second following a night of sleep deprivation, and the third after a successive full night's sleep. During the baseline examination, depressives showed a relatively negative cognitive bias; that is, the same number of positive and negative self-scheme elements. In comparison to controls, they showed significantly more negative and significantly less positive self-scheme elements. The same pattern emerged in a word recognition task for the number of recognized self-scheme elements. These variables indicated no change in the depressive group following sleep deprivation. Depressive subjects' reaction times on self-descriptiveness rating were significantly longer for positive than for negative self-scheme elements at the baseline session. The opposite was true for controls. Here, a sleep deprivation effect was evident. There was no longer a difference in the speed of information processing for positive as compared to negative self-scheme elements. This applied to both depressive and control groups.

Adult↗
PubMed1996

[Anxiety in alcohol-dependent patients].

Alcoholism and anxiety disorders are concomitant far more frequently than might be expected. The great prevalence of anxiety disorders in alcoholics constitutes an important clinical issue because alcoholic subjects with a coexisting anxiety disorder suffer more frequent and more severe relapses than nonalcoholic control subjects. The former also how greater liability to psychotropic drug abuse and overdose behaviour, and are at greater risk of suicide. The type of relationship between alcohol dependence and anxiety disorders has considerable theoretical meaning. Four possible non-mutually exclusive ways of association are discussed: 1. the ingestion of alcohol may be an attempt at self-medication of anxiety symptoms; 2. anxiety and alcohol abuse may, independent of each other, be based on a third underlying, possibly genetic, factor; 3. anxiety may be a toxic effect of alcohol abuse or of withdrawal; 4. anxiety may result from cognitive processes in connection with alcohol abuse or withdrawal. Clinical guidelines for the pharmacotherapy of anxiety in patients suffering from alcoholism are outlined.

Alcoholism↗
PubMed1992

[Importance of calcium ions and calcium antagonists in affective psychoses].

Apart from the eminent changes in the neurotransmitter systems of the central nervous system, a disturbance of the calcium ion concentration may be of significance in the pathophysiology of affective psychoses. The present paper deals with the contribution of calcium ions in the generation of affective psychoses and discusses the calcium antagonism as a new strategy in the treatment of the disease. The following topics will be described: 1. Disturbances of calcium metabolism in affective psychoses, 2. a comparison of lithium and carbamazepine effects, 3. clinical studies with organic calcium channel blockers in affective psychoses and 4. the role of calcium ions in affective psychoses.

Affective Disorders, Psychotic↗
PubMed1991

Anti-depressants and anti-convulsants for the treatment of neuropathic pain syndromes in cancer patients.

20 patients with neuropathic pain syndromes due to tumor-infiltration, who had not responded to conventional analgesics including strong opioids, received additional combination anti-convulsant and anti-depressant treatment. Pain amelioration occurred in all patients within median 46 h, and maximum effect was encountered within one week. Severe side effects were confined to three cases and were associated with carbamazepine treatment. Replacement by another type of anticonvulsants in 6 cases with either no response or intolerable side effects was successful in 5 patients, both in terms of efficacy and tolerability. One patient stopped taking AD/AC after 48 h.

Analgesics↗
PubMed1990

Frequency-dependent secretion of pancreatic amylase, lipase, trypsin, and chymotrypsin during vagal stimulation in rats.

Pancreatic enzyme secretion in rats has been shown to be stimulated differentially by the intestinal hormones secretin and cholecystokinin. Since it is unknown if activation of neural mechanisms have similar effects, it was the aim of the present study to examine in anesthetized rats the output of the pancreatic enzymes amylase, lipase, trypsin, and chymotrypsin before (15 min), during, and after (30 min each) vagal stimulation (5 ms, 10 V) with different frequencies (0.5, 5, 10, and 50 Hz). At 5 Hz, a maximal stimulation of all four enzymes was observed, with a peak towards the end of the vagal stimulation period. At 0.5 Hz, amylase, trypsin, and chymotrypsin were released not only in smaller quantities but also in a different time pattern (trypsin and chymotrypsin), with a maximum early during vagal stimulation. Lipase secretion remained unchanged at 0.5 Hz. At 10 Hz, the output of amylase, lipase, and trypsin was quantitatively less compared to 5 Hz. In contrast to stimulation at 0.5 and 5 Hz, the maximal enzyme output was reached after cessation of vagal stimulation (amylase and lipase). Chymotrypsin release did not change in response to vagal stimulation at 10 Hz. A frequency of 50 Hz had no influence on the secretion of any of the four enzymes determined. These data demonstrate that activation of the vagus nerves can lead to a differential release of pancreatic enzymes. The exact regulatory mechanisms of action are as yet unknown and remain to be determined.

Amylases↗