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Biomedical subjects

P Müller

Publications and source records attributed to P Müller.

At least 307 records · Page 17Linked to original sources
PubMed1990

alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure.

Protein phosphatase 2A (polycation-stimulated protein phosphatase L) was purified from porcine kidney and skeletal muscle. The 36-kDa catalytic and the 65-kDa putative regulatory (hereafter termed PR65) subunits of protein phosphatase 2A2 were separated by reverse-phase HPLC. Partial amino acid sequence data (300 residues) was obtained for PR65. Molecular cloning showed that two distinct mRNAs (termed alpha and beta) encoded the PR65 subunit. The cDNA encoding the alpha-isotype spanned 2.2 kilobases (kb) and contained an open reading frame of 1767 bases predicting a protein of 65 kDa, which was in good agreement with the size of the purified protein. The cDNAs encoding the beta-isotype contained an open reading frame of size similar to that of alpha-form but lacked an initiator ATG. Northern analysis, using RNA isolated from several human cell lines, indicated that the alpha-isotype was encoded by a mRNA of 2.4 kb that was much more abundant than the beta mRNA of 4.0 kb. Comparison of the predicted amino acid sequences of the two isotypes revealed 87% identity. The deduced protein sequences of the alpha- and beta-isotypes were found to be made up of 15 imperfect repeating units consisting of 39 amino acids. This repeating structure was conserved between species.

Amino Acid Sequence↗
PubMed1990

[Acute unilateral blindness as the initial symptom of meningeosis lymphomatosa].

The development of Meningeosis lymphomatosa is a rare event even in high grade Non-Hodgkin's lymphoma, often without any typical clinical signs. We report a case, where a unilateral sudden loss of vision was the first symptom of meningeosis lymphomatosa and indicated a generalized relapse in the patient, who seemed so far to be in complete remission.

Abdominal Neoplasms↗
PubMed1990

[Incidence of goiter and thyroiditis in chronic inflammatory rheumatism].

In our investigations 201 patients with rheumatoid arthritis show in 127 cases according 63.2% (123 women = 71.1%; 4 women = 14.3%) and 32 patients with collagen diseases in 11 cases according 34.4% (11 women = 43.3%) a goiter. In comparison to a control group with a goiter incidence of 29.5% in women (168 out of 570 women), we found in female patients with rheumatoid arthritis or collagen diseases a clearly higher prevalence of goiter. But there was no difference of goiter frequency between the small groups of men. A second aim of our study was to investigate, whether an increased occurrence of the hypertrophic kind of Hashimoto's thyroiditis is to find in patients with rheumatic diseases, because of a possible association of two immunological induced affections. The results of sonographical, immunological and cytological examinations of the thyroid gland suggested no high responsibility of Hashimoto's thyroiditis for the goiter frequency in rheumatism. Only in three out of 201 investigated patients with rheumatoid arthritis (1.5%) we were able to diagnose this disease. In comparison to a rheumatologically healthy population out of the same catchment area (HT-frequency less than 0.5%), indeed the morbidity rate in rheumatic patients seems to be 3 times higher. But for a goiter frequency of altogether 63.2% in this disease the Hashimoto's thyroiditis is only of very small importance. Other causes such as pharmacotherapy with goitrogenic antirheumatic drugs, conditions of iodine deficiency, disposition and probably also an increase of thyroid growth stimulating immunoglobulins may be alone or in combination or a much higher degree responsible for goiter development in patients with rheumatoid arthritis or collagen diseases.

Adolescent↗
PubMed1990

Depressive syndromes in schizophrenic patients after discharge from hospital. ANI Study Group Berlin, Düsseldorf, Göttingen, Munich.

A total of 364 schizophrenic outpatients who were stabilized for 3 months on continuous neuroleptic therapy after discharge from the hospital were rated according to three different scales for depressive syndromes (Brief Psychiatric Rating Scale anxious depression factor, AMDP/depression, and the self-rating PD-S depression scale). Between 19.5% and 27.5% of the patients were rated as depressed, or 35.7%-42.8%, when mild depressive syndromes were included. There were low, but significant correlations between demographic or life-event data and depression scores on the self-rating scale, whereas fewer correlations were found on the observer ratings. No associations were found between social adjustment and depression. Moderate correlations were found between measures of the apathetic syndrome and depression ratings, while observer ratings showed higher correlations than the self-rating. High depression scores, especially in the observer ratings, correlated with scales for global psychopathological assessment (CGI, GAS). There were significant correlations between extrapyramidal rigidity and observer rating depression scores, whereas the total amount of neuroleptics given had no influence. These results are interpreted on the basis of hypotheses about depressive syndromes in schizophrenia.

Antipsychotic Agents↗
PubMed1990

Effect of increased donor age on kidney transplant outcome.

Donors over the age of 50 years provided kidneys for 28 of our 226 recipients (12.4%) transplanted from January 1, 1987 to December 31, 1988. Immediate function following transplantation occurred in 36% of the kidneys from donors both over and under the age of 50. The overall 3-month graft survival rate for transplants from donors over 50 years was 89%, compared with 78% for transplants from donors under 50 years (p greater than 0.05). Thus kidneys from well-selected older donors make an important contribution to the total pool of organs available for transplantation.

Age Factors↗
PubMed1990

The use of transdermal nicotine in smoking cessation.

The transdermal administration of nicotine by means of a transdermal nicotine system (TNS) affords a novel way of nicotine replacement to alleviate smoking cessation. The plasma levels of nicotine maintained with the TNS are in the range of the footpoint concentrations observed in smokers. The efficacy of the TNS was investigated in two placebo-controlled double-blind smoking cessation programs with minimal contact and minimal psychological support. A total of 311 smokers were treated for 3 months or 9 weeks. The abstinence rates at the end of the treatment and weaning periods were almost doubled in the TNS groups (36% and 39%) as compared to the placebo groups (23% and 20%) with a significant difference for both studies (p less than 0.05). These data suggest that the TNS can also improve the smoking cessation rates under the conditions of general medical advice, making it suitable for use outside of specialized smoking cessation centers.

Administration, Cutaneous↗
PubMed1990

Specific bradycardic agents. 1. Chemistry, pharmacology, and structure-activity relationships of substituted benzazepinones, a-new class of compounds exerting antiischemic properties.

Structural modification of the calcium-antagonist verapamil (1) by replacement of the lipophilic alpha-isopropylacetonitrile moiety by various heterocyclic ring systems has led to a new class of cardiovascular compounds which are characterized by a specific bradycardic activity. These agents reduce heart rate without binding to classical calcium channels or beta-adrenoceptors, interacting instead specifically with structures at the sino atrial node. Therefore they have also been termed sinus node inhibitors. The prototype falipamil (2) has been submitted to further optimization mainly by manipulation of the phthalmidine moiety. This has resulted in a second generation of specific bradycardic agents with increased potency and selectively and prolonged duration of action represented by the benzazepinone-derivative UL-FS 49 (4). Structure-activity relationships within this novel class of compounds have revealed a marked dependence of activity on the substitution pattern of the aromatic rings, the nature of the central nitrogen atom, and the length of the connecting alkyl chains. The crucial role of the benzazepinone ring for bradycardic activity can be best explained by its special impact on the overall molecular conformation.

Animals↗
PubMed1990

Induction of frameshift mutations by caffeine in Escherichia coli K12.

Caffeine induced reversions of five different frameshift mutations in Escherichia coli K12. Only those mutations which were very sensitive to reversion-induction by 9-amino-acridine (9AA) were also sensitive to caffeine. Caffeine mutagenesis was not due to inhibition of cellular repair functions, but to the production of replication errors, which were corrected very efficiently by mismatch repair. From the results reported here we conclude that the targets for caffeine mutagenesis are long runs of GC base pairs, and that this mutagen induces -1 frameshifts.

Aminoacridines↗
PubMed1990

Strong antimutagenic effect of caffeine on 9-aminoacridine-induced frameshift mutagenesis in Escherichia coli K12.

Caffeine, present at a concentration of 3 mg/ml during treatment with 100 microM 9-aminoacridine (9AA) of wild-type Escherichia coli K12, caused a decrease in the yield of frameshift reversions of more than three orders of magnitude. Antimutagenesis of caffeine was shown to be due to partial inhibition of induction by 9AA of frameshift replication errors, resulting in an increased efficiency of mismatch repair of the pre-mutations produced under these conditions.

Aminacrine↗
PubMed1990

Single intravenous administration of the H+, K(+)-ATPase inhibitor BY 1023/SK&F 96022--inhibition of pentagastrin-stimulated gastric acid secretion and pharmacokinetics in man.

The effects of H+, K(+)-ATPase inhibitor BY 1023/SK&F 96022 on pentagastrin-stimulated acid secretion have been studied in healthy male volunteers (n = 12). The gastric acid response to submaximal pentagastrin-stimulation (0.6 micrograms/h/kg b.w.) was dose-dependently inhibited. A single dose of 5 mg decreased acid output by 22% while after 60 mg and 80 mg secretion was almost completely abolished. A good dose linearity was observed for AUC (0, infinity) and Cmax over the dose range from 5 to 80 mg. Elimination half-life, total clearance and volume of distribution of the parent compound were independent of the dose. The drug was well tolerated up to the highest dose of 80 mg. No clinically relevant influence was found on either laboratory screen or cardiovascular parameters.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

Effect of repeated oral administration of BY 1023/SK&F 96022--a new substituted benzimidazole derivative--on pentagastrin-stimulated gastric acid secretion and pharmacokinetics in man.

Pentagastrin stimulated gastric secretion was measured in 12 healthy male subjects after repeated once daily oral administration of 20 and 40 mg BY 1023/SK&F 96022--a new substituted benzimidazole derivative. Twenty milligrams inhibited acid output compared with placebo by 24% (2.5-3.5 h) and 26% (24.5-25.5 h) after the first oral intake. Inhibition increased to 56% and 50%, respectively, after the seventh oral dose. Forty milligrams inhibited acid output by a mean of 51% (2.5 to 3.5 h) and 52% (24.5-25.5) after the first oral intake. After the seventh dose mean inhibition rose to 85% and 66%, respectively. The drug was well tolerated, no drug-related changes in clinical laboratory, ECG, heart rate and blood pressure were observed. Fasting gastrin serum concentrations tended to increase with both doses, the mean values being within the normal range. AUC, Cmax and t1/2 of the drug after repeated oral intake were not significantly different when compared with a single dose at either 20 mg or 40 mg.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

[Diagnosis of rejection after pancreatic transplantation in the minipig model].

An allogenic transplantation of the total-pancreas with duodenum was carried out in the minipig model. The oral duodenum was closed blindly and the aboral part was led out as a stoma. The portal vein of the transplant was anastomosed end-to-side in the inferior vena cava and the celiac artery of the transplant in the distal aorta. Investigations for early diagnosis of rejection were carried out in this model parallelly respectively one by one. CT/MRT, selective angiography, laboratory chemical parameters were unsuitable for early detection. The pancreatic succus cytology and nuclear medical investigations show reproducible changes caused by rejection before the blood-sugar level was increased.

Amylases↗
PubMed1990

[Effective prevention of piroxicam-induced lesions of the gastric mucosa with nizatidine].

12 healthy volunteers participated in this single-blind, randomized, cross-over study. All subjects were given Piroxicam 20 mg mane on three different 14 days treatment periods in the presense of Nizatidine 150 or 300 mg bid and placebo respectively. Only subjects without endoscopically revealed gastroduodenal lesions were enrolled into the study. Endoscopy was repeated at day 14 of therapy. Between treatment periods a 2 weeks wash out phase was interposed. The gastroduodenal lesion score was the following: score 0 = no injury, score 1 = erythema, score 2 = less than or equal to 9 lesions, score 3 = greater than or equal to 10 lesions (petechiae/erosions), score 4 = ulcer. The mean lesion score with Piroxicam averaged 1.5 +/- 0.35 (+/- SEM) when placebo was coadministered. The mucosal lesion scores were reduced to 0.17 +/- 0.08 and 0.42 +/- 0.19 (+/- SEM) when Nizatidine 150 or 300 mg bid was given concurrently. This protection afforded by Nizatidine was significant when compared with placebo (p less than 0.01). The difference between the two Nizatidine doses, however, did not reach statistical significance. Our data suggest that Nizatidine markedly improves the gastroduodenal tolerability of Piroxicam.

Adult↗
PubMed1990

[Pharmacokinetics and tolerability of telenzepine in patients with compensated liver cirrhosis].

Pharmacokinetics and Tolerability of Telenzepine in Patients with Chronic Liver Diseases. The pharmacokinetics and tolerability of the new selective muscarinic M1-antagonist telenzepine (BY 803; CAS 80880-90-6) were studied in 10 patients with compensated liver cirrhosis who were treated over 4 weeks with 3 mg at night. 3 mg telenzepine was well tolerated. There was no deterioration of laboratory parameters during the 4 weeks treatment course. Following a single oral dose of 3 mg telenzepine the mean maximal plasma level (cmax) averaged 5.7 (1.9-10.1) ng/ml. After repeated dosing 3 patients displayed different kinetic behaviour resulting in higher values of AUC on day 14/15 in comparison to day 1/2. tmax and cmax remained unchanged. It can be concluded that even in patients with compensated liver cirrhosis no significant accumulation of the compound will occur.

Adolescent↗
PubMed1990

[Use of OKT-3 in treatment of rejection following kidney transplantation].

Application of OKT-3 as rescue therapy in steroid-resistant rejection was effective in 7 out of 9 patients early after cadaveric kidney transplantation. Under attention of instructions for use of OKT-3 the adverse first-dose reactions are rare. The problem of OKT-3 therapy is early use and its reuse.

Adult↗
PubMed1990

Pentagastrin-stimulated gastric acid secretion and pharmacokinetics following single and repeated intravenous administration of the gastric H+, K(+)-ATPase-inhibitor pantoprazole (BY1023/SK&F96022) in healthy volunteers.

The objective of the study was to investigate the pharmacodynamics and pharmacokinetics of the gastric H+, K(+)-ATPase inhibitor pantoprazole in man following repeated i.v. dosing. 8 healthy male volunteers aged from 25 to 31 years (median: 29 years), body weight between 72 and 95 kg (median: 82 kg) entered this single-blind two-period cross-over study. Each subject underwent two treatment periods of 5 days each with daily infusion of 15 mg or 30 mg pantoprazole, respectively. A placebo day preceeded the trial. On the placebo day as well as on days 1, 4 and 5 of each treatment period, gastric secretion was stimulated submaximally by a pentagastrin infusion of 0.6 micrograms/h/kg over a period of 4 h, starting one hour before administration of drug or placebo. Repeated once-daily infusion (15 min) of pantoprazole resulted in a rapidly increasing pharmacodynamic effect: as compared to placebo the mean percent inhibition of acid output measured from 1 to 3 h after start of infusion was 22%, 63% and 78% for the 15 mg dose, and 56%, 97% and 99% for the 30 mg dose on days 1, 4 and 5, respectively. The pH also increased in relation to the dose and the duration of treatment. Mean fasting gastrin serum concentrations increased by about 50%, yet remained within the normal range. Only in one subject, one of the individual values was above the upper limit of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1990

[3 mg telenzepine nocte in the treatment of benign stomach ulcer disease: a double-blind comparative study with 300 mg ranitidine nocte].

163 patients with endoscopically proven benign gastric ulcers were randomly allocated to treatment with either telenzepine 3 mg nocte or ranitidine 300 mg nocte for up to 8 weeks in a prospective double-blind study. The two groups were similar with regard to age, sex, number of patients with ulcer recurrence, smoking habits etc. After 4 weeks treatment 51/80 patients (64%) healed on telenzepine 3 mg nocte and 49/83 patients (59%) on ranitidine 300 mg nocte. The corresponding healing rates after 8 weeks were 85% (68/80) on telenzepine and 89% (74/83) on ranitidine. At each time there was no statistical difference between the two groups. After 8 weeks of treatment 58 patients (73%) on telenzepine and 72 patients (87%) on ranitidine were totally free from stomach pain (n.s.). Other ulcer related symptoms such as fullness etc. were more rapidly relieved with ranitidine. Anticholinergic side effects occurred significantly more frequent in patients on telenzepine than in patients on ranitidine. Dry mouth was the most frequent side effect in the telenzepine group. Telenzepine 3 mg at night appears to be as good as ranitidine 300 mg at night in the healing of benign gastric ulcer disease.

Adolescent↗