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Biomedical subjects

B Steiner

Publications and source records attributed to B Steiner.

At least 127 records · Page 7Linked to original sources
PubMed1992

[Psychosocial factors and follow-up of depressive disease].

In a one-year follow-up study 187 inpatients were studied using structured and semistructured interviews (Diagnostic Interview Schedule, Münchner Ereignisliste, Social Interview Schedule). In order to predict the course of depression we focused on psychosocial factors and their influence on the course of depression. The severity of depression at discharge and negative life events during the follow-up period could be identified as the main influence factors. Results suggest reciprocal influence between illness and social conditions, especially illness and marital relations. Marital dysfunctioning at follow-up was reported significantly more often by patients with unfavourable outcome, whereas patients who recovered did not differ from the control group in their marital conditions. The results suppose the value of social variables in the prediction of the course of illness. A few implications on these findings for therapeutic process are discussed.

Adult↗
PubMed1991

Ca(2+)-dependent structural transitions of the platelet glycoprotein IIb-IIIa complex. Preparation of stable glycoprotein IIb and IIIa monomers.

The platelet membrane glycoprotein (GP) IIb-IIIa complex is the receptor for adhesive proteins on activated platelets that mediates platelet aggregation. In the present study, factors affecting the structural stability of the purified GP IIb-IIIa complex and the dissociated subunits were investigated. Purified GP IIb-IIIa was incubated in various Ca2+ concentrations, and the percentage of dissociated subunits was quantitated by sucrose gradient sedimentation. Two Ca(2+)-dependent transitions were observed, one at about 60 microM Ca2+, where half of the complexes became dissociated, and the other at 0.1 microM Ca2+, where half of the dissociated subunits became incapable of reforming heterodimer complexes when higher Ca2+ concentrations were readded. This loss in ability to reform heterodimer complexes was caused primarily by a Ca(2+)-dependent transition in GP IIIa, leading to an apparent unfolding of this subunit, followed by the formation of high molecular weight aggregates. The formation of these aggregates was time- and temperature-dependent and could not be reversed by added Ca2+. Although Mg2+ prevented dissociation of GP IIb-IIIa, it failed to promote reassociation of the dissociated subunits. Based on these findings, conditions were developed for the preparation of dissociated GP IIb and GP IIIa such that 70% of the subunits remained functional in that they retained the ability to reform heterodimer complexes.

Calcium↗
PubMed1991

[Psychopathologic and psychophysiologic follow-up of inpatient depressed patients with standardized treatment with clomipramine and oxaprotiline].

The aim of this study was to show psychopathological and especially psychophysiological data of depressed inpatients which were collected during a 28-day double-blind study with 68 depressed inpatients given clomipramine 150 mgr/die) or maprotiline/oxaprotiline 150 mgr/die). Using Hamilton-Depression-Scale, Self-depression-scale (SDS by Zung), Beschwerdeliste (BL) and Befindlichkeitsskala (Bf-S) by v. Zerssen an impressive reduction of depression scores was observed in all rating scales with some superiority of clomipramine. But at the end of the study at treatment day 28 both groups - clomipramine and maprotiline/oxaprotilin - had similar results. During treatment each patient was part of a weekly habituation experiment using electrodermal activity in an orientation reaction as measure. Contrary to other studies (Lader 1975 or Heimann 1976, 1980) there was no difference in the course of psychophysiological data (EDA) between both treatment groups or between depressive agitation and psychomotor retardation. There was also no relationship between reactivity in EDA at study begin and treatment results.

Adult↗
PubMed1991

Marked suppression of gonadotropins and testosterone by an antagonist analog of gonadotropin-releasing hormone in men.

To study the dose response characteristics of a gonadotropin-releasing hormone (GnRH) antagonist ([Ac-D2-Nal1,D4-Cl-Phe2,D3-Pal3,Arg5,dGlu6 (AA), d-Ala10] GnRH; Nal-Glu), 1.5 or 5.0 mg of Nal-Glu were administered to two groups of five normal men by daily subcutaneous injection for 21 days. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (T) were determined on multiple occasions before, during, and after the antagonist treatment. Five milligrams Nal-Glu markedly suppressed mean serum immunoreactive LH to a mean of 1.5 +/- 0.4 IU/L (+/- SEM), immunoreactive FSH to the limit of assay detection (1 IU/L), and lowered basal mean serum T to castrate range (less than 2 nmol/L). Serum bioactive LH levels also showed a marked decrease in the 5.0-mg group similar to that seen in immunoreactive LH levels. Amplitude of immunoreactive LH pulses was markedly reduced in the 5.0-mg group on day 21. A 1.5-mg dose of Nal-Glu transiently suppressed serum immunoreactive LH levels on day 1. There was a subsequent escape on the rest of the days sampled. Serum immunoreactive FSH levels were not significantly changed over the 21-day treatment period. Serum T levels were transiently suppressed only on day 1 paralleling immunoreactive LH suppression. No adverse systemic side effects occurred. Thus, the 5.0-mg dose of this GnRH antagonist provides a pharmacological means of markedly suppressing the hypothalamic-pituitary-gonadal axis and, therefore, has potential as a male contraceptive.

Analysis of Variance↗
PubMed1991

The combination of prednisone and colchicine in patients with primary sclerosing cholangitis.

Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of the biliary tract. The cause of the disease is unknown, and no effective medical treatment exists. In this study, 12 patients received a combination of low-dose prednisone (10 mg/day) and colchicine (0.6 mg bid). Their course was compared with that of a group of concurrent historical controls. At 6 and 12 months, there was significantly more improvement in liver test results over baseline values in patients receiving prednisone and colchicine than in the untreated controls. At 24 months, however, no significant differences in biochemical tests were appreciated between treated and untreated patients. Analysis of serial liver biopsies showed no differences in histologic change in the two groups. During the 2 yr of follow-up, there were two deaths in the control group but none in the treated group. Four untreated patients developed ascites; gastrointestinal bleeding developed in three untreated patients, one of whom developed ascites. In contrast, in the treated group, ascites and bleeding developed in only one patient. We conclude that the combination of colchicine and prednisone does not retard histologic progression or progression of standard liver tests after 2 yr of therapy. There is a trend toward less clinical deterioration and improved survival after 2 yr of treatment. On the basis of these findings, we would not advocate empiric use of these drugs for patients with primary sclerosing cholangitis, but suggest that, if they are to be used at all in PSC, they be evaluated in a controlled clinical trial as treatment for this as yet incurable disease.

Adult↗
PubMed1990

Phosphorylation of microtubule-associated protein tau: identification of the site for Ca2(+)-calmodulin dependent kinase and relationship with tau phosphorylation in Alzheimer tangles.

The microtubule array in neuronal cells undergoes extensive growth, dynamics and rearrangements during neurite outgrowth. While little is known about how these changes are regulated, microtubule-associated proteins (MAPs) including tau protein are likely to perform an important role. Tau is one of the MAPs in mammalian brain. When isolated it is usually a mixture of several isoforms containing between 341 and 441 residues that arise from alternative splicing. Tau can be phosphorylated by several protein kinases. Phosphorylation at certain sites results in major structural and functional changes, as seen by changes in electrophoretic mobility, interaction with microtubules, molecular length and elasticity. Here we show that the sites of phosphorylation by four kinases (PKA, PKC, CK and CaMK) all lie in the C-terminal microtubule-binding half of tau, but only the phosphorylation by CaM kinase shows the pronounced shift in electrophoretic mobility characteristic for tau from Alzheimer neurofibrillary tangles. By using a combination of limited proteolysis, protein sequencing and protein engineering we show that a single phosphorylation site is responsible for this shift, located at Ser 405 in the C-terminal tail of the protein outside the region of internal repeats. Phosphorylation at this site not only reduces the electrophoretic mobility of tau, it also makes the protein long and stiff, as shown earlier. The site is likely to be phosphorylated in tau from Alzheimer neurofibrillary tangles.

Alzheimer Disease↗
PubMed1990

Nutritional and metabolic effects of gonadotropin-releasing hormone agonist treatment for prostate cancer.

Cancer commonly leads to weight loss associated with increased glucose production and protein breakdown. Medical or surgical castration results in decreased muscle mass, increased fat mass, and weight gain. The aim of this study was to evaluate the changes in body composition, protein metabolism, hepatic glucose production, (HGP), and basal energy expenditure in 10 men with advanced stage C and D prostate cancer receiving a gonadotropin-releasing hormone (GnRH) agonist (Buserelin). Metabolic parameters and nutritional status were determined at 0, 2, 6, and 12 months of therapy. Baseline measurements of plasma leucine appearance (76.2 +/- 5.4 microM/kg/h) and HGP rates (80.1 +/- 2.9 mg/m2/min) were greater than previously reported for normal volunteers. GnRH agonist therapy in prostate cancer patients was associated with a significant reduction in serum testosterone, dihydrotestosterone (DHT), luteinizing hormone (LH), and cortisol, and significant increases in triiodothyronine (T3) and free triiodothyronine (free T3). Neither basal energy expenditure nor plasma leucine appearance rates were changed over time, but there were significant linear reductions in HGP rates (80.1 +/- 2.9 mg/m2/min, mean +/- SEM; 79.9 +/- 2.3, 73.7 +/- 3.4, 72.5 +/- 2.3; P less than .01; baseline, 2, 6, and 12 months, respectively, by repeated measures ANOVA). In all patients, significant increases in body weight, triceps skin fold, cholesterol, and fat mass were noted. Total body water content was not significantly increased after the 12-month period; therefore, the weight gain seen in these patients was water-free tissue, ie, fat mass.

Aged↗
PubMed1990

Unusual features of integrated cDNAs generated by infection with genome-free retroviruses.

We previously demonstrated that when nonretroviral RNAs are encapsidated in retroviral particles they can be reverse transcribed into cDNAs, which are then integrated into the cellular genome. This transfer of genetic information via retroviral infection has been designated retrofection. Further analyses of three genes transferred in this manner (retrogenes) revealed that each was present in a single copy at a different site in the recipient quail cell genome and included a transcriptional promoter encoded by the encapsidated neo RNA. A unique feature of the retrogenes was a common 16-nucleotide sequence at or near a recombination border, which was not present in either recombination partner. The existence of this sequence suggests a common mechanism of retrogene formation and/or integration mediated by retrofection.

Animals↗
PubMed1990

Suicide risk in suicidal versus nonsuicidal depressed inpatients.

Depressed patients seem to be the prototype of patients with a higher suicide risk. Therefore, it is important for clinicians in psychiatric hospitals dealing with depressed inpatients as well as with depressed schizophrenic or alcoholic patients, to get a clear idea of the nature of suicide proneness among these inpatients. Results from different studies done by the Weissenau Depression Treatment and Research Group concerning the special issue of suicide proneness in depressed patients show that a "suicidal depressive syndrome" can best be described on a cognitive level by feelings of worthlessness, anxiety, and depressive delusions, and also by more sleep disorders and more past suicidal behavior.

Crisis Intervention↗
PubMed1989

Ca2+-dependent binding of a synthetic Arg-Gly-Asp (RGD) peptide to a single site on the purified platelet glycoprotein IIb-IIIa complex.

The platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa) is a member of the integrin receptor family that recognizes adhesive proteins containing the Arg-Gly-Asp (RGD) sequence. In the present study the binding characteristics of the synthetic hexapeptide Tyr-Asn-Arg-Gly-Asp-Ser (YNRGDS, a sequence present in the fibrinogen alpha-chain at position 570-575) to purified GP IIb-IIIa were determined by equilibrium dialysis. The binding of 125I-YNRGDS to GP IIb-IIIa was specific, saturable, and reversible. The apparent dissociation constant was 1.0 +/- 0.2 microM, and the maximal binding capacity was 0.92 +/- 0.02 mol of 125I-YNRGDS/mol of GP IIb-IIIa, indicating that GP IIb-IIIa contains a single binding site for RGD peptides. The binding of 125I-YNRGDS to purified GP IIb-IIIa showed many of the characteristics of fibrinogen binding to activated platelets: the binding was inhibited by fibrinogen, by the monoclonal antibody A2A9, and by the dodecapeptide from the C terminus of the fibrinogen gamma-chain. In addition, the binding of 125I-YNRGDS to GP IIb-IIIa was divalent cation-dependent. Our data suggest that two divalent cation binding sites must be occupied for YNRGDS to bind: one site is specific for calcium and is saturated at 1 microM free Ca2+, whereas the other site is less specific and reaches saturation at millimolar concentrations of either Ca2+ or Mg2+. The results of the present study support the hypothesis that the RGD domains within the adhesive proteins are responsible for their binding to GP IIb-IIIa.

Amino Acid Sequence↗
PubMed1988

[Initial clinical experiences in a large Austrian patient sample with immunodeficiency syndrome (AIDS): I. Type and course of encountered infections].

This study presents a report on the first clinical experiences gained in 68 hospitalized HIV antibody-positive patients from Austria, covering a period of twelve months. 36 patients (52.9%) belonged to risk group I or Ib (homo- or bisexual), whereas 26 (38.2%) patients were i.v. drug abusers (risk group II). 5 (7.4%) patients fulfilled the criteria of stage II of the CDC classification of HIV-associated clinical symptoms, 10 (14.7%) were classified as stage III and the remaining 53 patients (78%) as stage IV. The most frequent and also the most serious problem was the development of opportunistic infections. Multiple infections were found in 45.7% of all cases. Kaposi's sarcoma was found in 9 patients who all belonged to risk group I. During the entire observation period 10 patients died as a consequence of HIV-1-induced immunodeficiency and the resulting opportunistic infections and/or neoplasms.

Acquired Immunodeficiency Syndrome↗
PubMed1988

CGP 12.103 A versus clomipramine in the treatment of depressed inpatients--results of a double-blind study.

In a double-blind study, which was conducted as an interindividual comparison, 41 depressed inpatients were divided into two test groups according to a randomized list and received either the test substance CGP 12.103 A (19 patients) or the comparative substance clomipramine (22 patients). The study was conducted over a period of 28 days and the dosage of each substance, after being gradually increased, was stabilized at 150 mg. Except for a significantly varied distribution of syndrome patterns, the two treatment groups were comparable with regard to relevant criteria. Both treatment groups showed a significant improvement as assessed by both the degree of severity of depression and the Hamilton Depression Rating Scale; on each scale, however, the clomipramine treatment group exhibited a tendency toward better antidepressive efficacy. According to the self-evaluations of the patients, which were conducted with the help of v. Zerssen's Self-Rating Scale, this tendency was not significant. The Kusta activation parameter indicated a tendentially stronger manifestation in the case of clomipramine. In the final evaluation the onset of efficacy for the CGP 12.103 A group lay in the mean on treatment day 6, for the clomipramine group on treatment day 10. The physician's overall assessment of therapeutic effect found no differences between the two treatment groups on day 14 and on day 28. Expected side effects were observed in the CGP 12.103 A group in nine patients, in the clomipramine group in 14. All in all, the test substance CGP 12.103 A, the (-) or R-enantiomer of the antidepressant oxaprotiline, which itself is derived from maprotiline, showed no essential differences in its antidepressive efficacy compared with clomipramine.

Anthracenes↗
PubMed1987

Comparison of cDNA-derived protein sequences of the human fibronectin and vitronectin receptor alpha-subunits and platelet glycoprotein IIb.

The fibronectin receptor (FnR), the vitronectin receptor (VnR), and the platelet membrane glycoprotein (GP) IIb-IIIa complex are members of a family of cell adhesion receptors, which consist of noncovalently associated alpha- and beta-subunits. The present study was designed to compare the cDNA-derived protein sequences of the alpha-subunits of human FnR, VnR, and platelet GP IIb. cDNA clones for the alpha-subunit of the FnR (FnR alpha) were obtained from a human umbilical vein endothelial (HUVE) cell library by using an oligonucleotide probe designed from a peptide sequence of platelet GP IIb. cDNA clones for platelet GP IIb were isolated from a cDNA expression library of human erythroleukemia cells by using antibodies. cDNA clones of the VnR alpha-subunit (VnR alpha) were obtained from the HUVE cell library by using an oligonucleotide probe from the partial cDNA sequence for the VnR alpha. Translation of these sequences showed that the FNR alpha, the VnR alpha, and GP IIb are composed of disulfide-linked large (858-871 amino acids) and small (137-158 amino acids) chains that are posttranslationally processed from a single mRNA. A single hydrophobic segment located near the carboxyl terminus of each small chain appears to be a transmembrane domain. The large chains appear to be entirely extracellular, and each contains four repeated putative Ca2+-binding domains of about 30 amino acids that have sequence similarities to other Ca2+-binding proteins. The identity among the protein sequences of the three receptor alpha-subunits ranges from 36.1% to 44.5%, with the Ca2+-binding domains having the greatest homology. These proteins apparently evolved by a process of gene duplication.

Amino Acid Sequence↗
PubMed1987

Synthetic peptides derived from fibrinogen and fibronectin change the conformation of purified platelet glycoprotein IIb-IIIa.

The glycoprotein IIb-IIIa complex (GP IIb-IIIa) is a platelet cell-surface receptor for fibrinogen and fibronectin. A carboxyl-terminal decapeptide of the fibrinogen gamma-chain (Leu-Gly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val LGGAKQAGDV] and a tetrapeptide (Arg-Gly-Asp-Ser (RGDS] from the fibrinogen alpha-chain and the fibronectin cell-binding domain appear to mediate the binding of these ligands to GP IIb-IIIa. The present study was designed to examine the effects of these and related peptides on the structure of purified platelet GP IIb-IIIa. Treatment of GP IIb-IIIa with various synthetic peptides affected the glycoprotein so that GP IIb alpha became a substrate for hydrolysis by thrombin. The order of potency of these peptides was as follows: RGDS greater than LGGAKQAGDV greater than KGDS greater than RGES. This is the same order of potency in which these peptides inhibit fibrinogen binding to platelets. This effect was time-, temperature-, and concentration-dependent; RGDS induced a half-maximal effect at approximately 60 microM. In addition, RGDS, but not RGES, decreased the intensity of the intrinsic protein fluorescence of GP IIb-IIIa. Finally, the decapeptide or RGDS decreased the sedimentation coefficient of GP IIb-IIIa from 8.5 to 7.7 or 7.4 S, respectively, whereas RGES had a minimal effect. This decrease was accompanied by an increase in the Stoke's radius from 74 to 82 A with RGDS or 85 A with the decapeptide, indicating a peptide-induced unfolding of the GP IIb-IIIa complex. This change in conformation may be related to changes in the distribution and function of GP IIb-IIIa on the platelet surface that occur when adhesive proteins or peptides from the GP IIb-IIIa binding domains of these proteins bind to GP IIb-IIIa.

Binding Sites↗
PubMed1987

Protein sequence of endothelial glycoprotein IIIa derived from a cDNA clone. Identity with platelet glycoprotein IIIa and similarity to "integrin".

Platelet membrane glycoprotein (GP) IIIa forms a Ca2+-dependent heterodimer complex with GP IIb. The GP IIb-IIIa complex constitutes the fibrinogen and fibronectin receptor on stimulated platelets. A biochemically and immunologically similar membrane glycoprotein complex is present on endothelial cells. A human umbilical vein endothelial cell cDNA library was screened using oligonucleotide probes designed from peptide sequences obtained from platelet GP IIIa. A cDNA clone was sequenced and found to encode a protein of 84.5 kDa. The translated endothelial cDNA contained five sequences that corresponded to peptide sequences in platelet GP IIIa, including the amino-terminal 19 residues. Thus, the endothelial and platelet forms of GP IIIa are apparently identical. Glycoprotein IIIa consists of a long amino-terminal extracellular domain with several potential N-linked glycosylation sites and four cysteine-rich tandem repeats, a 29-residue hydrophobic transmembrane segment, and a short carboxyl-terminal cytoplasmic domain. Glycoprotein IIIa has a 47% amino acid sequence homology to "integrin," a fibronectin receptor from chicken embryo fibroblasts. This homology suggests that GP IIIa is a member of a family of cell-surface adhesion receptors.

Amino Acid Sequence↗
PubMed1987

Protein fingerprinting for the determination of relatedness in Acinetobacter calcoaceticus subspecies anitratus isolated from patients in a surgical intensive care unit.

The use of protein fingerprinting for the establishment of relatedness among isolates of Acinetobacter calcoaceticus subspecies anitratus, isolated from patients in a surgical intensive care unit was examined. Polyacrylamide gel electrophoresis was used to analyze the cellular proteins from whole cell lysates of 14 intensive care unit A calcoaceticus subspecies anitratus isolates and 11 control strains. Antimicrobial susceptibilities and plasmid profiles were also determined for all isolates. All intensive care unit A calcoaceticus subspecies anitratus isolates exhibited identical cellular protein fingerprints, no detectable plasmids, and minimum inhibitory concentrations within +/- 1 log2 dilution of the mode value for each of the antimicrobial agents tested. The other clinical isolates demonstrated a range of antimicrobial susceptibilities, various numbers and sizes of plasmids, and distinctly different protein fingerprints. These data indicate that protein fingerprinting may be useful as an epidemiologic tool in A calcoaceticus subspecies anitratus outbreaks and this method deserves further study.

Acinetobacter↗
PubMed1987

Delusional depression and suicide.

After a short survey of the relevant literature, the authors discuss the significance of delusional depression symptoms for suicidality, whereby they do not regard such symptoms alone as a sufficient condition for classifying a delusional patient as suicidal. In a comparison of delusional depressed patients with a non-delusional control group (matched pairs), the former were adjudged to be significantly less suicidal than the control group and did not differ from the control group in regard to suicide frequency.

Delusions↗