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Biomedical subjects

R Müller

Publications and source records attributed to R Müller.

At least 505 records · Page 28Linked to original sources

[Status of data of HLA-typed donors for unrelated bone marrow transplantation in Hannover: organization and results].

The pool of HLA-A, B and C-typed blood donors in Hannover for cell-donation increased from 2162 in 1988 to 2406 in 1989. 1032 blood donors declared their readiness to donate thrombocytes; 667 would like to donate bone marrow, 453 of them have undergone complete HLA-A, B, C and DR-typing. Until August 31, 1989 we looked in our data bank for an HLA-identical bone marrow donor for 84 patients from other transplantation centers and for 19 patients who are being looked after in Hannover and in national and international data banks.

Blood Donors↗

[Preoperative treatment with beta-receptor blockers and isoflurane anesthesia. Hemodynamic interactions in patients with coronary disease].

Although many patients undergoing general anesthesia and surgery are pretreated with beta-adrenoceptor blocking drugs, hemodynamic interactions of beta-blockers and volatile anesthetics have so far only been studied in animals. We therefore designed a clinical study to evaluate the relationship between the extent of preoperative beta-adrenoceptor blockade and the hemodynamic effects of isoflurane anesthesia. Sixty-one patients with coronary artery disease (CAD) and normal global left ventricular function scheduled for elective myocardial revascularization were studied immediately prior to surgery. One group of patients (n = 39) had been treated with beta-adrenoceptor blocking agents for at least 3 weeks up to and including the day of surgery. The degree of clinical beta-adrenoceptor blockade was quantified using the isoproterenol sensitivity test. The dose of isoproterenol required to increase heart rate by 25 beats/min was defined as the chronotropic dose 25 (CD25), representing the degree of beta-adrenoceptor blockade. Hemodynamic data were collected before and during isoflurane anesthesia (0.5%-0.6% end-tidal) plus 50% nitrous oxide. Twenty-two patients without preoperative beta-blocker therapy served as a control group. Preanesthetic values of cardiac index (CI), heart rate (HR) and mean arterial pressure (MAP) were lower in patients pretreated with beta-blocking drugs, but statistically these differences were not significant when compared to data obtained in unblocked patients. Isoflurane anesthesia caused significant reductions of CI and arterial blood pressure. However, there were no significant differences in the absolute values or the percentage changes compared to baseline data obtained in awake patients between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

[A modified Sarafoff suture for closure of the uterine wound in Cesarean section].

Using a retrospective investigation the authors demonstrate the advantage of the modified Sarafoff-suture (a one layer suture of the myometrium) in comparison with the two-layer suture. The results shows a lower rate of febrile courses, less postoperative complications and a shorter hospital stay. The first clinical experiences showed less scar complications in the courses of vaginal delivery in patients with a previous caesarean section. Therefore, the authors advise the modified Sarafoff-suture for wound closure in caesarean section.

Cesarean Section↗

[Noninvasive detection by Doppler and M-mode echocardiography of acute rejection reaction after heart transplantation: preliminary results of a prospective study].

Diagnosis of acute cardiac allograft rejection is still based on the results of endomyocardial biopsy. The objective of this study was to evaluate changes of left ventricular (LV) diastolic function associated with rejection using Doppler and M-mode echocardiography. The study patients, consisting of 29 cardiac allograft recipients (12 female, 17 male) aged 27 to 58 (mean 41) years, were classified into two groups on the basis of histopathologic findings: 13 patients without rejection (mean age 40 years) and 16 patients with moderate to severe allograft rejection (mean age 42 years) at myocardial biopsy. All patients underwent serial echocardiographic examination 4-10 weeks after transplantation and 8 +/- 2 days later on the day of myocardial biopsy. Twenty-five healthy volunteers (11 female, 14 male; mean age 39 years) served for assessing normal values. Echocardiographic assessment included peak velocity (PEV), pressure half-time (PHT), velocity-time integral (VTI-E) of early mitral flow (E-wave), and isovolumic relaxation period (IVRP). In transplant recipients, significantly higher values as compared to normals were found for PEV (72 vs 55 cm/s; p less than 0.01), PHT (51 vs 42 ms; p less than 0.001), VTI-E (71 vs 56 mm; p less than 0.001), and IVRP (91 vs 73 ms; p less than 0.001). During rejection, heart rate increased significantly from 78 to 93 beats/min (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

[Treatment of chronic hepatitis B with interferon alpha-2b].

A total of 58 patients with histologically confirmed chronic viral hepatitis B and presence of HBsAg and HBV-DNA in the serum were randomized in a prospectively controlled trial. 30 patients were treated with 3 megaunits of rIFN a-2b s.c. thrice weekly for 4 months. 28 controls received no treatment. The post-treatment follow-up period consisted of 6 months. 28 patients treated and 27 controls completed the protocol. One female patient of the treatment group showed a complete response (loss of HBsAg, HBeAg and HBV-DNA), 8 other patients (32%) revealed a partial response to therapy (loss of HBeAg and HBV-DNA). Three patients of the control-group (11%) lost HBeAg and HBV-DNA spontaneously. This finding is statistically significant (p less than 0.05). The elimination of HBV-markers from the serum was associated with a normalization of aminotransferase activities in the serum. A reactivation of hepatitis was not observed after seroconversion.

Adolescent↗

[Cardiac involvement within the scope of HIV-1 infection: preliminary results of echocardiography study].

The results of one- and two-dimensional echocardiography in 128 patients (117 males, 11 females; median age 37 years) who were seropositive for HIV-1 were analyzed in addition to clinical, electrocardiographic, and laboratory data. Follow-up controls are available for 51 patients over an observation period of 1 to 24 months, median 9.5 months. Probably HIV-related echocardiographic abnormalities were identified in 36 patients (28%): small to moderate pericardial effusions (n = 34) and left ventricular dilation (n = 5). Pericardial effusions resolved in seven patients during follow-up, in three cases after tuberculostatic chemotherapy. Compared to patients without cardiac involvement patients with HIV-related echocardiographic abnormalities showed lower CD4-lymphocyte counts (143 +/- 138 vs 289 +/- 219/microliters, p less than or equal to 0.01), and left ventricular endsystolic dimensions were increased (34.2 +/- 4.5 vs 32.6 +/- 3.0 mm, p less than or equal to 0.05). Cardiac involvement occurred predominantly in the advanced stages of the HIV-1 infection with unclear etiology in the majority of cases, even though active concomitant diseases could be frequently demonstrated. The clinical course of some patients might be consistent with intercurrently completed perimyocarditis, probably of viral genesis. CD4-lymphocyte counts less than or equal to 100/microliters could be identified as a risk factor for the development of cardiac manifestations. The significance of a demonstrated involvement of the heart with regard to therapeutic consequences and prognosis appeared to be slight. Use of echocardiography as a routine method for the detection of cardiac involvement in HIV-1 infection has proved to be valuable, since indicative clinical symptoms were lacking in almost all cases.

Adult↗

[Prospective study of primary and secondary prevention of Pneumocystis carinii pneumonia with pentamidine aerosol].

In an open prospective study in the AIDS Outpatient Department of the Frankfurt University Clinic the efficacy of pentamidine aerosol at a dosage of 200 mg every 14 days in the primary and secondary prophylaxis of pneumocystis carinii pneumonia was tested. The incidence of pneumocystis carinii pneumonia was reduced by more than 75% in the group of patients receiving pentamidine additionally by inhalation as compared with a historical cohort given azidothymidine alone. The results of the study suggest that a CD4-positive cell count of less than 50/microliters with a concomitant secondary lung infection promotes the development of pneumocystis carinii pneumonia. There was no correlation between the incidence of pneumocystis carinii pneumonia and the number of previous disease episodes. No systemic toxicity of pentamidine aerosol was established.

AIDS-Related Complex↗

trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation.

Fos protein can trans-activate AP-1-dependent gene expression and trans-repress the c-fos promoter. Although we find that trans-repression is enhanced by coexpression of c-Jun, it does not require any of the AP-1 or ATF sites in the mouse c-fos promoter. A major target for repression is the serum response element (SRE). Fos mutants with an impaired leucine zipper are defective in trans-repression and transformation, suggesting that these functions involve the formation of Fos protein complexes. In contrast, mutations that abolish DNA binding of Fos enhance trans-repression but destroy the transforming potential of Fos. In addition, v-Fos protein efficiently transforms but is unable to trans-repress. These findings point to different mechanisms involved in trans-activation and trans-repression and suggest that trans-repression of the type described here is neither sufficient nor required for Fos-induced transformation.

Animals↗

Asymmetrical recognition of the palindromic AP1 binding site (TRE) by Fos protein complexes.

Fos and Jun proteins form a tight complex which binds specifically to the AP1 recognition sequence, a palindromic DNA element also referred to as the TPA responsive element (TRE). To elucidate the mechanism of Fos-Jun interaction with the TRE we have performed UV cross-linking studies using oligonucleotides where thymines were replaced with bromouracil. Our results indicate that both Fos and Jun directly contact the TRE but that the interaction of Fos and Jun with thymines in structurally equivalent positions in the two half sites of the TRE is different. In addition, we have carried out a comprehensive mutagenesis study of the TRE by introducing all possible point mutations plus thymine----uracil substitutions into the palindromic TRE core sequences and the adjacent nucleotides on both sides. The results of this analysis clearly show that the palindromic TRE is asymmetrical with respect to binding of Fos-Jun. We also show that a Fos protein complex with a homodimeric DNA binding site binds considerably less efficiently to TRE mutants with a perfect dyad symmetry compared with the binding to the wild-type TRE. This demonstrates that the asymmetrical recognition of the TRE is not due to the heterodimeric nature of the Fos/Jun complex but directly related to an asymmetry in the TRE sequence. The methyl groups of all four thymine residues within the TRE seem to be functionally crucial since thymine----uracil substitutions strongly reduce or abolish binding to Fos/Jun. The relevance of structurally equivalent methyl groups in the TRE core sequence is different, lending further support to the conclusion that the TRE is asymmetrical.

Animals↗

Tellurium-intoxication.

Tellurium is one of the rarest elements on earth. Intoxications are rare and almost exclusively occupationally exposed workers are affected. Only a few cases of non-occupational poisoning have been reported so far. Severe poisoning results in respiratory depression and circulatory collapse. After occupational exposure main symptoms and signs include loss of appetite, dryness of the mouth, suppression of sweating, a metallic taste in the mouth, and most notable, a sharp garlic odor of the breath, sweat and urine. We report our findings in a 37 year old, non-occupationally exposed woman with tellurium intoxication.

Adult↗

Unusually rapid development of a HBsAG-positive liver cirrhosis after liver transplantation.

We report the case of a 44-year-old man who was transplanted in 1986 for hepatocellular carcinoma in a HBsAG-positive liver cirrhosis. The patient had no severe complications postoperatively. He received passive immunization for the prevention of hepatitis B reinfection during the first 6 months after liver grafting. Twelve months after the transplantation the new liver was reinfected with hepatitis B virus. Without any clinical or laboratory signs of severe hepatitis, the patient developed a histologically proven complete liver cirrhosis within 8 months after reinfection of the graft. The reasons for this might have been, first, a deleterious course of the infection under immunosuppressive therapy, and, second, the additional influence of a postoperatively acquired CMV infection or the combined toxic influence of cyclosporin A and its metabolites on the acute inflammation in the liver.

Adult↗

A Fos protein containing the Jun leucine zipper forms a homodimer which binds to the AP1 binding site.

The TPA (12-O-tetradecanoyl-phorbol-13-acetate) responsive element (TRE) is recognized by the inducible transcription factor AP1, a heterodimeric complex of Fos- and Jun-protein subunits, which each contain a specific structure known as the leucine zipper through which they interact. Studies using site-directed mutagenesis have shown that a basic region adjacent to the leucine zipper in Fos is crucial for the interaction of the Fos-Jun complex with the TRE, and probably represents a site of interaction with DNA. The functionally crucial amino acids in this region are almost completely conserved between Fos and Jun (refs 6, 7 and 11; M.N. and R.M., unpublished results), indicating the formation of a nearly symmetrical DNA-binding site in the Fos-Jun complex. Whereas Jun can form a homodimeric protein complex which binds to the TRE, Fos is unable to do so. The Fos-Jun heterodimer, however, possesses at least a 30-fold-higher affinity for the TRE than does the Jun-Jun homodimer, indicating cooperative binding. Because Fos cannot form a homodimer it is not known whether Fos specifically recognizes part of the TRE or has a different role in the binding of the Fos-Jun complex to DNA. Here we report that exchanging the leucine zipper in Fos with that of Jun generates a protein (termed psi-Fos) that can form a complex with Fos. This Fos-psi-Fos complex, and to a lesser extent a homodimeric psi-Fos complex, exhibits specific binding to the TRE. This finding strongly supports the hypothesis that Fos and Jun form a nearly symmetrical DNA-binding site that interacts with the palindromic TRE.

Binding Sites↗