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Biomedical subjects

V Müller

Publications and source records attributed to V Müller.

At least 73 records · Page 4Linked to original sources
PubMed1998

Structure of the Na+-driven flagellum from the homoacetogenic bacterium Acetobacterium woodii.

The Na+-dependent flagellum of Acetobacterium woodii was characterised. Flagellin and whole flagella were purified and analysed by SDS-PAGE and electron microscopy. The structure and dimensions of the filament and the hook-basal body, as revealed by electron microscopy, resemble those of H+-dependent flagella from gram-positive bacteria. Intramembrane particle rings were present at the cell pole in freeze-fractured A. woodii cells, which might correspond to the mot complex.

Bacterial Proteins↗
PubMed1998

Plasma separation and bilirubin adsorption after complicated liver transplantation: a therapeutic approach to excessive hyperbilirubinemia.

BACKGROUND: Severe hyperbilirubinemia is known to exert multiple toxic effects. Thus, a reduction in bilirubin by use of various adsorbent columns has been reported for a variety of hepatic disorders, but no experience with liver transplant patients is available as yet. METHODS: Plasma separation and bilirubin adsorption by an anion-exchange adsorbent column (BR-350) were performed in two patients with severe jaundice (total serum bilirubin > 55 mg/dl) and multiple organ failure that had developed after orthotopic liver transplantation. RESULTS: The procedure resulted in an 18% to 35% reduction in total bilirubin after each session, accompanied by a remarkable clinical improvement. Both patients finally recovered and had a favorable outcome. No complications or side effects of bilirubin adsorption were observed during any of the six sessions. CONCLUSIONS: Bilirubin adsorption is a safe and effective treatment. It should be considered as supportive therapy for excessive hyperbilirubinemia after liver transplantation. In selected cases, retransplantation may thus be avoided.

Adsorption↗
PubMed1998

Partial antagonism between steroidal and nonsteroidal antiestrogens in human breast cancer cell lines.

Nonsteroidal antiestrogens, such as tamoxifen, are well established in the treatment of breast cancer. The development of new steroidal compounds without partial agonist activity allows deeper insights into the mechanism of antiestrogen action, but thus far, the combined use of steroidal and nonsteroidal antiestrogens has not been studied extensively. We compared the nonsteroidal 4-trans-hydroxytamoxifen (OHT) with the two steroidal antiestrogens, ICI 182780 and RU 58668, in the estrogen receptor-positive human breast cancer cell lines MCF-7 and T47D. The effect of each compound alone or of OHT in combination with one of the steroidal antiestrogens was studied in regard to cell proliferation, expression of estrogen receptors (ERs) and progesterone receptors, and secretion of transforming growth factor beta2 (TGF-beta2). All antiestrogens examined led to enhanced secretion of TGF-beta2, which is correlated with their individual growth-inhibitory potential. OHT partially counteracts the larger growth inhibition of human breast cancer cells exerted by the steroidal antiestrogens ICI 182780 and RU 58668. Also, OHT antagonizes the higher induction of TGF-beta2 seen after treatment of MCF-7 cells with steroidal antiestrogens. The loss of ER and down-regulation of progesterone receptor under treatment with the steroidal antiestrogens is prevented by OHT, whereas the steroidal antiestrogens prevent the ability of hydroxytamoxifen to increase the ER content. These results indicate that TGF-beta2 is a marker of action for both types of compounds, but steroidal and nonsteroidal antiestrogens partially antagonize each other in blocking ER-mediated cellular events. It would appear that no additive or synergistic effect of the two types of antiestrogens can be expected in the treatment of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Hypertension accelerates the pace of chronic graft dysfunction in the rat.

In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK-->SHR) or an SHR (SHR-->SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR-->SHR developed a significantly higher blood pressure than BBOK-->SHR. Blood pressure in BBOK-->BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK-->SHR) and SHR-->SHR kidneys as compared with the BBOK-->BBOK kidneys (P < 0.05). Infiltration of ED-1+ monocyte/macrophages and OX19 pan-T-cells was most pronounced in allografts (BBOK-->SHR) and was also increased in SHR-->SHR as compared with BBOK-->BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependent factors are of greater important.

Animals↗
PubMed1998

Do urinary tract infections trigger chronic kidney transplant rejection in man?

PURPOSE: Urinary tract infections are frequent after kidney transplantation but little is known about the impact on long-term survival. As chronic rejection is the major cause of graft loss in the long term, we retrospectively analyzed the role of urinary tract infections in this process. MATERIALS AND METHODS: We included in the study all adult patients who received kidney transplants at our unit between 1972 and 1991, which ensured followup of at least 5 years, and we focused on the relationship between urinary tract infections and the incidence of chronic rejection episodes. To analyze the influence of urinary tract infections on chronic rejection patients were separated into those in whom biopsy proved chronic rejection developed within the first 5 years after transplantation (chronic rejection group 225) and those without apparent signs of chronic rejection during that period (control group 351). The correlation between urinary tract infections per year and the incidence of chronic rejection was analyzed. RESULTS: Patients with chronic rejection had more urinary tract infections per year than controls. In the first year after transplantation both groups had the highest incidence of urinary tract infections but thereafter the rate of urinary tract infections per year declined. However, the incidence consistently remained higher in the chronic rejection group. This difference reached significance by year 3 after transplantation. Furthermore, a high rate of urinary tract infections correlated with an early onset of chronic rejection. CONCLUSIONS: Urinary tract infections are an important risk factor for the onset of chronic rejection, and early and intense treatment is critical.

Adult↗
PubMed1998

Effects of LHRH-analogues on mitogenic signal transduction in cancer cells.

The expression of luteinizing hormone-releasing hormone (LHRH) and its receptors has been demonstrated in a number of human malignant tumors, including cancers of the breast, ovary, endometrium and prostate. These findings suggest the presence of an autocrine regulatory system based on LHRH. Recent studies in our laboratory have demonstrated that the function of LHRH produced by ovarian cancer cells is the inhibition of their proliferation. Dose-dependent antiproliferative effects of LHRH-agonists have been observed by several laboratories in cell lines derived from the above cancers. Interestingly, also LHRH-antagonists have marked antiproliferative activity in most of the ovarian, breast and endometrial cancer cell lines tested so far, indicating that the dichotomy of LHRH-agonists/LHRH-antagonists is not valid for the LHRH-system in cancer cells. In addition, our data suggest that the classical LHRH receptor signal transduction mechanisms known from the pituitary (phospholipase-C, protein kinase C, adenylyl cyclase) are not involved in the mediation of LHRH effects in cancer cells. Data obtained by several groups, including ours, rather suggest that LHRH analogs interfere with the signal transduction of growth-factor receptors and related oncogene products associated with tyrosine-kinase activity. The mechanism of action is probably an LHRH-induced activation of a phosphotyrosine phosphatase, counteracting the effects of receptor associated tyrosine kinase. In our hands, LHRH analogs virtually blocked the EGF-induced MAP-kinase activity of ovarian and endometrial cancer cells. The pharmacological exploitation of this mechanism might provide promising new therapies for these cancers.

Cell Transformation, Neoplastic↗
PubMed1998

Intestinal and systemic humoral immunological events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs.

The aim of the study was to investigate the systemic and, for the first time, the intestinal humoral events in the susceptible Balb/C mouse strain after oral administration of Echinococcus multilocularis eggs. Thirty-one mice were divided into three groups; W-2, W-8 and control group. Each mouse of the W-2 and W-8 groups was orally infected with 1,500 E. multilocularis eggs, two weeks and eight weeks before sacrifice respectively. Control group mice received phosphate buffer saline. Measurement of anti-E. multilocularis and non-specific IgG, IgA and IgM, and of a transudation marker, albumin, were performed in serum and intestinal washings by a time-resolved immunofluorometric assay. These results were complemented by microscopic examination of the intestinal mucosa. This infection model is well-suited to the study of mucosal immunity during alveolar echinococcosis. It showed a major specific intestinal response in the early stage of the disease whereas the systemic response predominated later in the disease. Histopathological studies and calculation of the relative coefficient of excretion of Ig also confirmed that the presence of the parasite, even during a short period, was responsible for a local immunological and inflammatory response and for a change in mucosal permeability. Mucosal immunity could thus play a role in tolerance induction against E. multilocularis that could be a prerequisite for the subsequent development of the larvae in the liver, and for the occurrence of the parasitic disease, alveolar echinococcosis.

Animals↗
PubMed1998

The A1A0 ATPase from Methanosarcina mazei: cloning of the 5' end of the aha operon encoding the membrane domain and expression of the proteolipid in a membrane-bound form in Escherichia coli.

Three additional ATPase genes, clustered in the order ahaH, ahaI, and ahaK, were found upstream of the previously characterized genes ahaECFABDG coding for the archaeal A1A0 ATPase from Methanosarcina mazei. ahaH, the first gene in the cluster, is preceded by a conserved promoter sequence. Northern blot analysis revealed that the clusters ahaHIK and ahaECFABDG are transcribed as one message. AhaH is a hydrophilic polypeptide and is similar to peptides of previously unassigned function encoded by genes preceding postulated ATPase genes in Methanobacterium thermoautotrophicum and Methanococcus jannaschii. AhaI has a two-domain structure with a hydrophilic domain of 39 kDa and a hydrophobic domain with seven predicted transmembrane alpha helices. It is similar to the 100-kDa polypeptide of V1V0 ATPases and is therefore suggested to participate in proton transport. AhaK is a hydrophobic polypeptide with two predicted transmembrane alpha helices and, on the basis of sequence comparisons and immunological studies, is identified as the proteolipid, a polypeptide which is essential for proton translocation. However, it is only one-half and one-third the size of the proteolipids from M. thermoautotrophicum and M. jannaschii, respectively. ahaK is expressed in Escherichia coli, and it is incorporated into the cytoplasmic membrane despite the different chemical natures of lipids from archaea and bacteria. This is the first report on the expression and incorporation into E. coli lipids of a membrane integral enzyme from a methanogens, which will facilitate analysis of the structure and function of the membrane domain of the methanoarchaeal ATPase.

Amino Acid Sequence↗
PubMed1998

[Long-term HIV infection and dialysis dependent renal failure in analgesic nephropathy].

We report a case of advanced human immundeficiency virus infection and relapsing urinary tract infections due to analgesic nephropathy. The patient developed an urosepsis with multiorgan dysfunction syndrome and required dialysis. Inspite of this complicated course, for the first time thirteen years after diagnosis of the HIV-infection, an antiretroviral treatment was started, followed by an impressive improvement of quality of life, physical activity and psychological stabilization.

Analgesics↗
PubMed1998

[Plasma separation and bilirubin adsorption therapy in excessive hyperbilirubinemia after liver transplantation].

Reduction of bilirubin levels by various means has been proposed as symptomatic therapy for excessive jaundice in various end-stage liver diseases, since it exerts multiple toxic effects and may thereby promote multiple organ failure. Plasma separation and bilirubin adsorption by an anion-exchange column (BR-350) performed in four patients with excessive hyperbilirubinemia after liver transplantation resulted in a 29%-70% reduction in total serum bilirubin, accompanied by significant improvement of multiple organ failure or encephalopathy in three patients. Bilirubin adsorption may be beneficial in complicated jaundice after hepatic transplantation and should further be evaluated for its clinical indications.

Hemoperfusion↗
PubMed1997

Mutagenesis of some positive and negative residues occurring in repeat triad residues in the ADP/ATP carrier from yeast.

In AAC2 from Saccharomyces cerevisiae, nine additional charged residues (six positive, three negative) were neutralized by mutagenesis following the previous mutation of six arginines. Oxidative phosphorylation (OxPhos) in cells and mitochondria, the expression level of AAC protein, and the various transport modes of AAC in the reconstituted system were measured. Mutations are: within the first helix at K38A which is exclusive for AAC; K48A, and R152A, part of a positive triad occurring in the matrix portion of each repeat; two matrix lysines, K179M and K182I, and the negative triad helix-terminating residues, E45G, D149S, D249S. Cellular ATP synthesis (OxPhos) is nearly completely inhibited in K48A, R152A, D149S, and D249S, but still amounts to 10% in K38A and between 30% and 90% in the gly+ mutants K179M, K179I + K182I, and E45G. Comparison of the AAC content measured by ELISA and the binding of [3H]CAT and [3H]BKA reveals discrepancies in K48A, D149S, and D249S mitochondria, which provide evidence that these mutations largely abolish inhibitor binding. Also these mitochondria have undetectable OxPhos. Differently in K38A, CAT and BKA binding are retained at high AAC levels but OxPhos is very low. This reveals a special functional role of K38, different from the more structural role of R152, K48, D149, and D249. Transport activity was measured with reconstituted AAC. The electroneutral ADP/ADP exchange of gly- mutants is largely or fully suppressed in K48A, D149S, and D249S. K38A and R152A are still active at 18% and 30% of wt. The other three exchange modes, ATP/ADP, ADP/ATP, and ATP/ATP, are nearly suppressed in all gly- mutants but remain high in gly+ mutants. ATP-linked modes are higher than the ADP/ADP mode in gly+ but lower in gly- mutants, resulting in an exchange mode inversion (EMI). In the competition for AAC2 transport capacity, the weak ATP exporting modes are suppressed by the much stronger unproductive ADP/ADP mode causing inhibition of OxPhos. Together with previous results all members of three charge triads are now mutagenized, revealing drastic functional rotatory asymmetries within the three repeat domains. In the intrahelical arginine triad the third (R294A), in the positive matrix triad the second (R152A), and in the helix-terminating negative triad the first (E45G) still show high activity.

Adenosine Triphosphate↗
PubMed1997

Metabolic factors have a major impact on kidney allograft survival.

BACKGROUND: At the present time, late graft loss is the major cause of kidney failure after transplantation. However, the influence of metabolic factors on this process is ill-defined. METHODS: To identify the impact of lipid metabolism, glucose metabolism, and blood pressure and their prognostic value for graft survival, data for all recipients of a kidney allograft with a potential graft survival of >15 years and a minimum graft survival of 1 month were analyzed retrospectively. Recipients of kidney grafts functioning more than 15 years (n=32) were compared with those with a graft function of less than 10 years (n=152, controls) and evaluated in a multivariate analysis. RESULTS: Low levels of serum cholesterol, triglycerides, and glucose, before and after transplantation, were accompanied by a prolonged graft survival. Prognostic factors for early graft failure included serum triglycerides >300 mg/dl, cholesterol >250 mg/dl before transplantation, serum creatinine >4.0 mg/dl 1 month after transplantation, and donor age above 45 or less than 10 years. Additionally, systolic and, particularly, diastolic blood pressure was lower in the group with a prolonged graft function as compared with controls immediately before and after transplantation. In addition, the incidence of primary graft function was lower and the incidence of acute rejection episodes higher in controls. Cold and warm ischemic time, body mass index, recipient age, and gender did not differ significantly. CONCLUSIONS: Our data suggest that metabolic parameters play an important role in the process of late graft loss after kidney transplantation.

Adult↗
PubMed1997

Endocrine testicular function in HIV-infected outpatients.

We investigated endocrine testicular function in 100 HIV-infected men who were grouped according to the CDC criteria. Progression of the disease was associated with a 27% decrease in plasma oestradiol, which was the only parameter that was weakly correlated with CD4 cell count (r = 0.312, p <0.05). Individual data showed a decreased plasma concentration of total and free testosterone in 35% and 26% of the subjects, respectively, but we could not demonstrate an increased frequency of hypogonadism going along with a progression of the stage of disease. There was no significant correlation between androgen, SHBG or FSH levels and duration of HIV-infection, BMI or CD4 cell count. Hypergonadotropic hypogonadism was associated with an euthyroid sick state in a 15% subgroup of patients reporting a decrease in libido. Plasma T3 was significantly correlated with testosterone (r = 0.419, p <0.01) and mean plasma T3 was significantly decreased in 8 subjects suffering from erectile impotence. Thus, hypogonadism occurs frequently in HIV-infected outpatients. Like euthyroid sickness it does not seem to be a predictor for progression of the disease but an indicator of actual state of health.

Adult↗
PubMed1997

Thyroid and adrenal function in HIV-infected outpatients.

We investigated parameters of thyroid and endocrine functions in 100 HIV-infected men who were grouped according to the CDC criteria. Progression of the disease was associated with a 44% increase in plasma TBG and a 15% increase in plasma CBG, while the T4/TBG ratio was decreased by 20%, plasma DHEAS was lowered by 30% and urinary aldosterone excretion fell by 70%. Plasma T4, T3 and TSH and urinary excretion of cortisol and catecholamines was not influenced by the disease. A weak, but significant negative correlation was found between plasma CBG and the body mass index of the patients. Significant positive correlations were observed between CD-4 cell count and the T4/TBG-ratio or plasma DHEAS levels. TBG was inversely correlated with CD-4 cell count and DHEAS. Thus, an increase in plasma TBG and a shift from adrenal androgen and mineralocorticoid steroid secretion towards cortisol secretion may be endocrine markers for progression of the disease in patients with HIV-infection.

Adrenal Glands↗
PubMed1997

Sequence of subunit c of the Na(+)-translocating F1F0 ATPase of Acetobacterium woodii: proposal for determinants of Na+ specificity as revealed by sequence comparisons.

A 3.2 kb EcoRI fragment carrying genes for Na(+)-F1F0 ATPase was cloned from chromosomal DNA of Acetobacterium woodii. DNA sequence analysis revealed the presence of an open reading frame which was identified by data base searches and comparison with the experimentally derived N-terminal amino acid sequence to code for subunit c of Na(+)-F1F0 ATPase. A comparison of the primary sequences of the two well established Na(+)-translocating F1F0 ATPases from Acetobacterium woodii and Propionigenium modestum with H(+)-translocating enzymes indicates the length of the C-terminus as well as specific residues located in the cytoplasmic membrane to be important for Na+ transport.

Amino Acid Sequence↗
PubMed1997

Short-term effects of behavioral treatment on movement initiation and postural control in Parkinson's disease: a controlled clinical study.

In a controlled clinical study, we investigated the effects of behavioral treatment on postural and gait initiation problems idiopathic Parkinson's disease (PD). Comparable groups of patients received therapy (experimental group, n = 15) and nonspecific psychological treatment (control group, n = 14) for 10 weeks. We monitored various variables reflecting properties of posture and gait initiation by using an optoelectronic motion analyzer (electronic movement analysis system, ELITE). A clinician blind to group membership of the patients assessed PD severity with the United Parkinson's Disease Rating Scale (UPDRS) before and after the treatment period. ELITE measures of postural stability and movement initiation revealed treatment-specific effects. In addition, UPDRS motor scores showed significant improvement only after behavioral treatment. We conclude that behavioral treatment in Parkinson's disease may improve motor disabilities in moderately advanced PD patients.

Aged↗