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Biomedical subjects

C Weise

Publications and source records attributed to C Weise.

At least 55 records · Page 3Linked to original sources
PubMed1994

All potential glycosylation sites of the nicotinic acetylcholine receptor delta subunit from Torpedo californica are utilized.

All possible N-glycosylation sites of the delta subunit of the nicotinic acetylcholine receptor from Torpedo californica electric tissue are utilized. By a combination of microsequencing and mass spectrometry, it was shown that a high-mannose-type oligosaccharide is bound at Asn143 of the delta subunit. The oligosaccharides at positions Asn70 and Asn208 of the delta subunit are probably of the complex type. The utilized glycosylation sites pose restrictions on possible transmembrane folding models of the subunit.

Amino Acid Sequence↗
PubMed1994

Nefazodone and imipramine in major depression: a placebo-controlled trial.

Nefazodone is a phenylpiperazine antidepressant with 5-HT2 antagonism and 5-HT reuptake inhibition. Two hundred and eighty-three out-patients with a diagnosis of DSM-III-R major depression of at least one-month duration (65% ill for over 6 months), and a mean score of 24 on the 17-item Hamilton Rating Scale for Depression (HRSD), were randomised to treatment with nefazodone, imipramine, or placebo. The double-blind treatment period was 8 weeks in duration. Nefazodone's antidepressant efficacy was comparable with imipramine's, with both drug treatments significantly better than placebo in a variety of outcome measures. For example, after 8 weeks of therapy, 78% of nefazodone and 83% of imipramine but only 55% of placebo patients (P < 0.01) were globally much or very much improved. Nefazodone was better tolerated than imipramine, with fewer drop-outs and a lower incidence of side-effects during treatment.

Adult↗
PubMed1993

Secondary structure and temperature behaviour of acetylcholinesterase. Studies by Fourier-transform infrared spectroscopy.

The secondary structure of the acetylcholinesterase and its temperature behaviour have been investigated using Fourier-transform infrared (FTIR) spectroscopy. The data are compared to the structure obtained by X-ray analysis of the crystalline enzyme. The secondary structure was determined using the spectral features observed in the amide-I band (H2O buffer) and amide-I' band (D2O buffer) at 1600-1700 cm-1, taking advantage of resolution-enhancement techniques along with least-squares band-fitting procedures. The relative amounts of different secondary-structure elements, 34-36% for alpha-helices, 19-25% for beta-sheets, 15-16% for turns and 13-17% for irregular structures, were estimated. These data, obtained with the enzyme in solution, correlate well with X-ray data of the crystalline protein [Sussman, J. L., Hard, M., Frolow, F., Oefner, C., Goldman, A., Toker, L. & Silman, I. (1991) Science 253, 872-879]. These results are also in good agreement with those obtained by computing the psi and phi angles of the peptide backbone using the Kabsch and Sanders method [Kabsch, W. & Sanders, C. (1983) Biopolymers 22, 2577-2637]. In conjunction with the X-ray data, two bands in the FTIR spectra were assigned to different populations of long and short alpha-helices. Until now this phenomenon has only been described by theoretical calculations [Nevskaya, N. A. & Chirgadze, Yu. N. (1976) Biopolymers 15, 637-648]. The relationship between the thermally induced loss of enzyme activity and secondary-structure changes has also been investigated. The decrease in enzyme activity to zero at 30-40 degrees C was accompanied only by minor changes in the secondary structure. At 55-60 degrees C, denaturation of AChE occurs. In this temperature range, all bands assigned to the various secondary-structure elements abruptly disappear in a co-operative and irreversible manner, whereas the beta-aggregation bands (at 1622 cm-1 and the corresponding high-frequency band) increase in intensity at the same rate.

Acetylcholinesterase↗
PubMed1992

Nuclear substrates of protein kinase C.

Starting from the finding that, for neuronal cells, the nuclear-membrane-associated protein kinase C (PKC) is the so-called 'membrane inserted', constitutively active form, we attempted to identify substrates of this nuclear PKC. For this purpose, nuclear membranes and other subcellular fractions were prepared from bovine brain, and in-vitro phosphorylation was performed. Several nuclear membrane proteins were found, the phosphorylation of which was inhibited by specific PKC inhibitors and effectively catalyzed by added PKC. Combining the methods of two-dimensional gel electrophoresis, in-situ digestion, reverse-phase HPLC and microsequencing, two of these nuclear PKC substrates were identified; the known PKC substrate Lamin B2, which serves as a control of the approach and the nucleolar protein B23. Our data suggest, that, for B23, Ser225 is a site of phosphorylation by PKC.

Amino Acid Sequence↗
PubMed1992

Investigation of ligand-binding sites of the acetylcholine receptor using photoactivatable derivatives of neurotoxin II from Naja naja oxiana.

Several photoaffinity derivatives of neurotoxin II from the venom of the central Asian cobra Naja naja oxiana have been prepared. After reaction of the 125I-labeled derivatives with the nicotinic acetylcholine receptor from electric organ, the alpha-subunit of the nAChR is almost exclusively labeled by the derivative carrying the photoactivatable group in position Lys46. In contrast to this, a reactive group at Lys26 predominantly labels the gamma- and delta-subunits, while the alpha- and beta-subunits incorporate much less radioactivity. Competition experiments with d-tubocurarine show that the gamma-subunit is labeled when this derivative occupies the high affinity d-tubocurarine-binding site, while the delta-subunit is labeled by the toxin bound at the low-affinity d-tubocurarine site. A model is discussed for the orientation of different loops of the toxin molecules in the binding site for agonists and competitive antagonists.

Animals↗
PubMed1992

The efficacy and safety of paroxetine compared with placebo in outpatients with major depression.

Paroxetine, a phenylpiperidine derivative, is an antidepressant that selectively inhibits serotonin reuptake. In this study 111 outpatients with major depression diagnosed by DSM-III criteria were treated with either paroxetine or placebo in a 6-week, randomized, double-blind study. Paroxetine was significantly superior to placebo on six of the seven major efficacy variables. Significant differences in favor of paroxetine were apparent by Week 2. Paroxetine was also well tolerated. These results support the efficacy and safety of paroxetine as a treatment for patients with major depression.

Adult↗
PubMed1991

Anionic subsites of the catalytic center of acetylcholinesterase from Torpedo and from cobra venom.

A peptide of acetylcholinesterase (AcChoEase; acetylcholine acetylhydrolase, EC 3.1.1.7) from the venom of the cobra Naja naja oxiana labeled by the affinity reagent N,N-dimethyl-2-phenylaziridinium (DPA) has been identified. The sequence is Gly-Ala-Glu-Met-Trp-Asn-Pro-Asn. In AcChoEase from Torpedo californica, a homologous peptide was labeled and isolated. Its sequence is Ser-Gly-Ser-Glu-Met-Trp-Asn-Pro-Asn, representing positions 79 through 87. In both cases labeling can be prevented by 0.1 mM edrophonium, indicating that the respective peptides form part of the anionic subsite of the catalytic center. The modified residue was tryptophan (Trp-84 in Torpedo AcChoEase) in both enzymes. In contrast to AcChoEase from Torpedo, the enzyme from cobra venom does not contain a peripheral anionic binding site.

Acetylcholinesterase↗
PubMed1991

Substrate-binding sites in acetylcholinesterase.

Acetylcholinesterase is among the most efficient enzymes known. In order to provide an explanation for its catalytic and regulatory mechanisms, including the high turnover rate, the specific amino acid residues involved in substrate binding and hydrolysis need to be identified. In this article, Ferdinand Hucho, Jaak Järv and Christoph Weise describe the topography of the enzyme as deduced from protein chemistry studies. One result of this approach is the finding that the binding pocket for the substrate's cationic cholinium group appears to be hydrophobic rather than anionic.

Acetylcholinesterase↗
PubMed1991

Adinazolam, diazepam, imipramine, and placebo in major depressive disorder: a controlled study.

In summary, the clinical results of this double-blind study clearly show that imipramine, as expected, demonstrated significant antidepressive properties in outpatients suffering from major depressive disorders. In contrast, adinazolam showed rather mild and weak antidepressive properties, and in no measures did its response differ significantly from that of diazepam. These findings are quite in contrast to those obtained by the authors in an earlier study with alprazolam (Rickels et al., 1987) in which alprazolam and imipramine produced rather similar results and both were significantly better than placebo, while diazepam was not. While the rather high dropout rate may well be considered a limitation of the study, the dropout rate is equally distributed between all four treatments. And since both decreasing sample size and endpoint analyses which include all patients with at least one week data, provide rather similar results, the findings can be considered as robust despite the high dropout rate. While the authors consider those findings the most robust in which endpoint and completer analyses results are rather similar, when high dropout rates occur, endpoint analyses should be given more weight than completer analyses as they are more representative of actual clinical practice. The present findings therefore suggest that adinazolam clearly possesses less antidepressive properties than imipramine and not more than diazepam and these findings are in agreement with other studies which found lack of significant antidepressant activity for such benzodiazepines as diazepam (Covi et al., 1974) and chlordiazepoxide (Lipman et al., 1986). The presence of only borderline antidepressive effects combined with rebound symptoms occurring already after only 6 weeks of therapy does not recommend adinazolam for use in depression.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

[Rational hormone diagnosis in normocyclic functional sterility].

Functional infertility in women with a normal menstrual cycle is the first symptom of a pathophysiological sequence of multiple different endocrinopathies. It usually progresses and leads to secondary amenorrhoea which is the most severe symptom of ovarian insufficiency. The percentage of abnormal hormonal parameters will increase with the duration and extent of the endocrinological aberration. The aim of this study is to examine the frequency of the different potential changes in hormone levels of an unselected group of female patients in a fertility clinic. 307 patients suffering from functional sterility (menstrual cycle 25-34 days) were investigated via basal hormone laboratory tests (including TRH test) under standardised conditions. 73 patients had pathological changes of the Fallopian tubes and in 116 patients their husbands had severe andrological problems. Excluded from this study were patients with bilateral occlusion of the Fallopian tubes and patients whose partners had a sperm count of less than 1 million/ml. The percentage of abnormal hormone levels (greater than mean + standard deviation + grey area) was 32.2% for prolactin (PRL), 7.8% for TSH, 20.9% for Delta-TSH, 18.4% for DHEA-sulfate (DS), 9.8% for testosterone (T), 18.9% for LH, and 11.5% for FSH (LH and FSH were specifically calculated only in 87 patients). In 65.5% of the patients the midluteal oestradiol (E2) and progesterone (P) levels were below normal, as sign of a corpus luteum insufficiency (CLI). A step- by-step diagnostic procedure would have yielded the following cumulative abnormal hormone levels retrospectively: (1) PRL (n = 99) = 32.2% (2) +TSH/delta TSH (n = 85) = 48.9% (3) +DS (n = 56) = 58.0% (4) +T (n = 30) = 59.3% (5) +LH/FSH (n = 28) = 62.2% [(6) +E2/P (n = 201) = 82.7%.] Only in 37.8% (116 patients) all hormone levels were within normal limits during the early follicular phase (FP); if the patients with signs of CLI are added, the percentage would be only 17.8% (n = 53). Case analysis demonstrated that functional sterility was accompanied by hyperprolactaemia in 32.4% of all patients, by abnormalities of the thyroid function (hypothyroidism 16.0%, hyperthyroidism 7.8%) in 23.8%, by hypothalamic and/or pituitary dysfunction in 28.7%, and by hyperandrogenaemia in 22.5%. Primary ovarian insufficiency was diagnosed in 4.6%. 31.3% of all patients (n = 307) had a combination of different hormonal abnormalities. The average duration of infertility among this group of patients was 6.3 years.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1991

Placebo-controlled trial of venlafaxine for the treatment of major depression.

Results are presented of the first double-blind, placebo-controlled trial of a novel antidepressant venlafaxine, which preclinically has demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects. Sixty outpatients meeting DSM-III-R criteria for major depression were randomized to receive 6 weeks of treatment with one of three fixed doses of venlafaxine--25 mg three times a day, 75 mg three times a day, or 125 mg three times a day--or placebo. Significant improvement was observed in depression scores at all doses, with the high dose resulting in earlier improvement, by week 2. For the combined venlafaxine treatment groups, 68% achieved a moderate or marked improvement on the Clinical Global Impression scale, compared with only 31% for the placebo group. Venlafaxine was well tolerated, and nervousness, sweating, and nausea were the only adverse effects observed more frequently with drug compared with placebo.

Adult↗
PubMed1990

Anionic subsites of the acetylcholinesterase from Torpedo californica: affinity labelling with the cationic reagent N,N-dimethyl-2-phenyl-aziridinium.

Several peptides of acetylcholinesterase of Torpedo californica labelled with the alkylating reagent [3H]N,N-dimethyl-2-phenyl-aziridinium (DPA) were localized within the primary structure. One peptide had the sequence KPQELIDVE (positions 270-278); the incorporation of DPA into this peptide could be specifically suppressed by propidium, which suggests that it is part of the peripheral anionic site. The incorporation of DPA into two other peptides was insensitive to propidium but could be prevented by edrophonium; the sequence of one of the peptides assumed to be part of the anionic site in the catalytic centre was found to be DLFR (positions 217-220). Decamethonium efficiently blocked alkylation by DPA in all three investigated peptides.

Acetylcholinesterase↗
PubMed1990

The active site and partial sequence of cobra venom acetylcholinesterase.

About 30% of the primary structure of acetylcholinesterase (AchE) from the cobra Naja naja oxiana has been determined. The sequence around the serine residue labeled by diisopropylfluorophosphate (DFP) was found to be TVTLFGESAGAASVGM which is similar to the active sites of AChE from other tissues. The part of the primary structure determined shows 76% identity with AChE from Torpedo and 42% identity with the Drosophila enzyme. A surprisingly large identity (42% in the sequence determined) was found with lysophospholipase from rat.

Acetylcholinesterase↗
PubMed1990

[Endocrinological diagnosis of normocyclic functional sterility].

Normocyclic functional sterility can be regarded as a starting point to the common pathophysiology of different endocrinopathies. Those are finally leading to secondary amenorrhoea, as the most severe sign of ovarian insufficiency. The incidence of abnormal hormonal parameter increases parallel to the duration and the extent of the respective endocrinopathy. For a better causal classification of the endocrine disorder a complete hormonal assessment is mandatory, as characteristic historical data or significant clinical signs will often be missed in infertile patients. The completion of one single basic hormonal examination might lead to an exact differentiated diagnosis and then allows accordingly for the induction of a purposeful treatment. The pregnancy rates are considerably high proving the effectiveness of the thoughtful pretherapeutic diagnostic evaluation. The principle of cost-effectiveness is as well maintained by the follow-up of complete diagnosis and master-tailored therapy.

Androgens↗
PubMed1990

What constitutes an adequate antidepressant trial for fluoxetine?

One hundred and eight patients with major depression were treated with fluoxetine 20 mg/day for 3 weeks. Patients who failed to respond to this open-label treatment were randomly assigned either to receive fluoxetine 60 mg/day for 5 weeks or to continue treatment with fluoxetine 20 mg/day for an additional 5 weeks. Both treatment groups demonstrated a statistically significant reduction in depressive symptoms, indicating that continued treatment with low-dose fluoxetine may be as effective as an increase in dose in achieving a favorable clinical outcome.

Adult↗
PubMed1989

A placebo-controlled, double-blind, clinical trial of paroxetine in depressed outpatients.

A placebo-controlled, randomized, double-blind study was carried out in outpatients suffering from major unipolar depressive disorder to assess the efficacy and tolerability of paroxetine in the treatment of depression. The study lasted for six weeks. After a placebo washout period of 4 to 14 days patients took 20mg of paroxetine or matched placebo as a morning dose for one week; thereafter the dose of paroxetine could be titrated between 10 and 50mg/day. Patients were evaluated at baseline, weekly during the first four weeks of the study, and at the end of six weeks; patients who entered a six-week extension phase were evaluated at 9 and 12 weeks. Evaluations were carried out using HAMD (including ECDEU factors), MADRS, HSCL, Covi anxiety and Raskin depression scales, CGI, and a seven-point rating of global improvement. Adverse events and laboratory values were also recorded at each assessment. One hundred and eleven patients entered the study, and efficacy data were available for 102 of these (49 on paroxetine and 53 on placebo). Efficacy measurements demonstrated significantly greater clinical improvement with paroxetine than placebo after two weeks of treatment, and this became even more marked after six weeks. Patients who continued treatment for a further six weeks maintained their clinical improvement. When adverse events were examined, statistically significant differences between paroxetine and placebo were seen only for sweating, diarrhoea, nausea, and somnolence. No significant changes were seen in any of the laboratory parameters measured. If these results are confirmed in future studies, paroxetine will represent an important addition to the treatments available for depression.

Adult↗
PubMed1985

Comparison of two dosage regimens of fluoxetine in major depression.

The effect of dose frequency on fluoxetine efficacy and safety was evaluated in a double-blind study in patients with major depressive disorder. The patients received fluoxetine once a day (in the morning) or twice a day (in the morning and at noon). There were no significant differences between the two groups in the mean measures of efficacy, all of which showed significant improvement over baseline (p less than .001). Adverse experience profiles were not significantly different, with nervousness/anxiety predominating in both groups. In the subsequent 48-week open-label study, the percentage of patients reporting adverse experiences decreased greatly.

Adult↗