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Biomedical subjects

W Muller

Publications and source records attributed to W Muller.

At least 37 records · Page 2Linked to original sources
PubMed1996

Endemic Tyrolean infantile cirrhosis: an ecogenetic disorder.

BACKGROUND: 138 infants and young children died from an endemic infantile liver cirrhosis in a circumscribed rural area of western Austria between 1900 and 1974. Frequency of the disease peaked between 1930 and 1960. It has disappeared from this area since 1974. METHODS: Clinical and genetic data on the patients was gathered; pedigrees analysed and ethnographic studies and interviews were undertaken. FINDINGS: The disease, which was clinically and pathologically indistinguishable from Indian childhood cirrhosis and hepatic copper toxicosis, was transmitted by autosomal recessive inheritance. Cow's milk, contaminated with copper from untinned copper or brass vessels, may have contributed to the development of copper toxicosis. Replacement of untinned copper cooking utensils by modern industrial vessels has eradicated the disease. INTERPRETATION: Our findings strongly suggest that the endemic Tyrolean childhood cirrhosis-and by analogy non-Wilsonian hepatic copper toxicosis occurring elsewhere-is an ecogenetic disorder requiring the involvement of both genetic and environmental factors for the disease to become manifest.

Animals↗
PubMed1996

Leishmania promastigotes selectively inhibit interleukin 12 induction in bone marrow-derived macrophages from susceptible and resistant mice.

Leishmania major promastigotes were found to avoid activation of mouse bone marrow-derived macrophages (BMM0) in vitro for production of cytokines that are typically induced during infection with other intracellular pathogens. Coexposure of BMM0 to the parasite and other microbial stimuli resulted in complete inhibition of interleukin (IL) 12 (p40) mRNA induction and IL-12 release. In contrast, mRNA and protein levels for IL-1(alpha), IL-1(beta), tumor necrosis factor (TNF) alpha, and inducible NO synthase (iNOS) were only partially reduced, and signals for IL-10 and monocyte chemoattractant protein (MCP-1/JE) were enhanced. The parasite could provide a detectable trigger for TNF-alpha and iNOS in BMM0 primed with interferon (IFN) gamma, but still failed to induce IL-12. Thus IL-12 induction is selectively impaired after infection, whereas activation pathways for other monokine responses remain relatively intact. Selective and complete inhibition of IL-12(p40) induction was observed using BMM0 from either genetically susceptible or resistant mouse strains, as well as IL-10 knockout mice, and was obtained using promastigotes from cutaneous, visceral, and lipophosphoglycan-deficient strains of Leishmania. The impaired production of the major physiological inducer of IFN-gamma is suggested to underlie the relatively prolonged interval of parasite intracellular survival and replication that is typically associate with leishmanial infections, including those producing self-limiting disease.

Animals↗
PubMed1996

Inhaled nitric oxide for avoidance of extracorporeal membrane oxygenation in the treatment of severe persistent pulmonary hypertension of the newborn.

UNLABELLED: Inhaled nitric oxide (NO) is thought to provide a noninvasive therapeutic alternative to extracorporeal membrane oxygenation (ECMO) in the treatment of persistent pulmonary hypertension of the newborn (PPHN). OBJECTIVE: Since January 1993, we have studied inhalation of NO in PPHN patients meeting the ECMO criteria of our institution. We focused on the questions of whether or not the need for ECMO could be obviated and whether differences could be found between NO responders and nonresponders. DESIGN: NO gas was delivered via conventional IPPV ventilation in incrementally increasing concentrations from 20 to 80 ppm. PATIENTS: NO therapy was attempted in ten ECMO candidates with clinical and echocardiographical evidence of PPHN (mean OI 51.9, SD 10.4). RESULTS: At various NO levels (30-60 ppm), five patients showed a significant increase in mean PaO2 (range 32.9-85.9 mmHg). Improvement was transient in three patients (6-10 h) and prolonged in two others (54-80 h); in the latter cases, ECMO was avoided. Five patients did not respond at all to treatment. Responders and nonresponders differed in their mean respiratory tidal volume (8.9 vs 4.18 ml/kg, P <0.05). CONCLUSIONS: In our study, inhalation of NO obviated the necessity of ECMO therapy in only two out of ten PPHN patients. Thus, we would discourage any overoptimistic expectations about the effectiveness of NO therapy in PPHN until larger clinical trials have been performed.

Administration, Inhalation↗
PubMed1995

Altered immune responses in mice lacking inducible nitric oxide synthase.

Nitric oxide (NO) is important in many biological functions. It is generated from L-arginine by the enzyme NO synthase (NOS). The cytokine-inducible NOS (iNOS) is activated by several immunological stimuli, leading to the production of large quantities of NO which can be cytotoxic. To define the biological role of iNOS further, we generated iNOS mutant mice. These are viable, fertile and without evident histopathological abnormalities. However, in contrast to wild-type and heterozygous mice, which are highly resistant to the protozoa parasite Leishmania major infection, mutant mice are uniformly susceptible. The infected mutant mice developed a significantly stronger Th1 type of immune response than the wild-type or heterozygous mice. The mutant mice showed reduced nonspecific inflammatory response to carrageenin, and were resistant to lipopolysaccharide-induced mortality.

Amino Acid Oxidoreductases↗
PubMed1995

IgA-alpha-1-antitrypsin complex in systemic lupus erythematosus: preliminary report.

To investigate the role of the complex IgA-alpha-1-antitrypsin (IgA-AT) in systemic lupus erythematosus (SLE) and in mixed connective tissue disease (MCTD), and its possible relations to either activity of the disease or a treatment, we examined a concentration of IgA-AT complex in 65 SLE and 9 MCTD sera. Complex IgA-AT was evaluated using a double antibody enzyme-linked immunoassay (ELISA). Twenty nine patients with SLE (44.6%) and three patients with MCTD (33.3%) had increased serum IgA-AT levels. The mean values of IgA-AT complex in patients with SLE and MCTD were higher than in healthy controls. Among the SLE group, patients with current neurological manifestation were characterized by an increase in IgA-AT serum concentration (2.45 +/- 2.07 U vs. 0.78 +/- 0.70 U, P < 0.001). No relation was found between this complex and ESR level, C-reactive protein (CRP) concentration, or hemoglobin level. Ten SLE patients were treated with CTX intravenously. In this group of patients, IgA-AT complex level was found to be increased compared with patients without such a treatment (1.82 +/- 1.30 U vs. 0.80 +/- 0.67 U, P < 0.05). The present study provides two new observations. Firstly, IgA-AT complex is increased in SLE and MCTD compared with healthy controls, and secondly, patients with CNS involvement displayed a striking increased IgA-AT level.

Adult↗
PubMed1994

Enantiospecific synthesis of bioactive hydroxyeicosatetraenoic acids (HETEs) in Hydra magnipapillata.

Recent reports have shown the occurrence of regiospecific and enantioselective lipoxygenase-mediated metabolism of arachidonic acid (AA) in cytosolic extracts of marine and freshwater hydroids. Here we report that cytosolic extracts of Hydra magnipapillata are unique among hydrozoans for their capability of converting AA into two major metabolites which showed chromatographic, mass spectrometric and nuclear magnetic resonance properties identical to those of 11-R- and 12-S-hydroxyeicosatetraenoic acid (11-R-HETE and 12-S-HETE). The production of neither compound was affected by co-incubation of H. magnipapillata extracts with the cytochrome P-450 inhibitor proadifen. The 5- and 12-lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA), while inhibiting 12-S-HETE formation at high concentrations, did not influence 11-R-HETE production, thus suggesting the co-localisation, unprecedented in hydroids, of two separate enantioselective lipoxygenase-like activities. The possible role of the two metabolites in the control of hydroid body pattern was investigated. At low micromolar concentrations, both enantiomers of 11-HETE inhibited diacylglycerol-induced ectopic head formation (EHF), while 12-S-HETE, and its likely precursor 12-S-hydroperoxy-eicosatetraenoic acid (12-S-HPETE), enhanced bud formation, thus providing the first example of endogenous metabolites controlling, respectively, hydroid 'head activation potential' and asexual reproduction.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1994

Cold-induced vasospasm in patients with fibromyalgia and chronic low back pain in comparison to healthy subjects.

Using capillary videomicroscopy of the nail fold, the frequency of cold-induced vasospasm and capillary hemodynamic parameters were studied after application of cold in 50 patients with primary fibromyalgia, 50 patients with chronic low back pain, and 50 healthy controls. Cold-induced vasospasm was detected in 38% of the patients with fibromyalgia. In this group it was significantly more frequent than in the patients with chronic low back pain (20%, p < 0.05) and healthy subjects (8%, p < 0.001). In the fibromyalgia group, the magnitude of vasospasm as measured by the capillary blood flow deceleration after cold application correlated negatively with the pain intensity as measured by pain score (r = -0.3839, p < 0.01). No differences in clinical appearance were found between patients with and without cold-induced vasospasm in both the fibromyalgia and low back pain group.

Adult↗
PubMed1994

Comparison of microheterogeneity of alpha-1-acid-glycoprotein in serum and synovial fluid from rheumatoid arthritis patients.

Microheterogeneity of alpha-1-acid glycoprotein was studied using affinity immunoelectrophoresis with concanavalin A as a ligand in the samples of serum and synovial fluid obtained at the same time from 22 patients with rheumatoid arthritis. Individuals with intercurrent infection or other illnesses were excluded from the study. The results were expressed as reactivity coefficient (RC). Disease activity was evaluated by Mallya-Mace Activity Score, Lansbury Joint Index and laboratory tests. In most of the studied samples the glycosylation pattern was similar, composed of a nonreactive variant and 2 reactive (the first and the second) with Con A variants. In seven samples of synovial fluid an extra third peak representative of the strongly reactive one with Con A fraction was observed. It was the cause of the remarkable elevation of AGP-RC. Moreover, the level of IgM and IgA RF was higher in the synovial fluid derived from these patients--with the presence of the third peak in AFF-EP with Con A--than in those without the considered fraction.

Adult↗
PubMed1992

Early prenatal diagnosis of type II cystic adenomatoid malformation of the lung: sonographic and histological findings.

Cystic adenomatoid malformation is a rare abnormality of the fetal lung. Depending on the size and histology of the cyst, it is classified as type I, II or III. With improving ultrasound technology, prenatal diagnosis during the mid-trimester is now possible; however, the earliest previous reports of type II cases have been at 23-24 weeks' gestation. We here report cases diagnosed at 19.5 and 20.5 weeks. In contrast to the appearance of multiple small cysts seen later in pregnancy, these cases showed a predominance of marked hyperechogenicity, usually associated with type III malformations, with small areas of lung involved by sonographically detectable cysts. Both families chose pregnancy termination. Sonographic findings, counselling, and histology are presented and discussed.

Journal Article↗
PubMed1992

Is indoramin an effective alternative to prostatectomy?

Alpha-1-adrenergic antagonists are recommended for symptomatic treatment of patients awaiting prostatic surgery. Their efficacy has been confirmed in placebo controlled clinical trials, but to date no comparison of their effects with the results of subsequent prostatectomy has been made. Fifty-five patients awaiting prostatectomy were assessed (by symptom scores and peak urinary flow rates) prior to treatment, on indoramin 20 mg bd, and 2 months following prostatectomy. Side effects while taking indoramin were experienced by 36% of patients. Despite an overall improvement in mean symptom scores, 26% of patients with obstructive and 30% of those with irritative symptoms who were assessed while taking indoramin failed to experience any improvement. Of the 31 patients assessed while on indoramin and again following surgery, prostatectomy produced a greater symptomatic relief than indoramin. The increase in peak flow rate following prostatectomy was 11.7 ml/s compared with 3.2 ml/s on indoramin. However, 5 patients preferred to continue taking indoramin rather than proceeding to surgery. Indoramin is no substitute for prostatectomy. Although some patients might benefit from treatment while awaiting surgery, significant side effects may severely restrict its use for this purpose. The response to indoramin cannot be used as an accurate predictor of response to prostatectomy.

Humans↗
PubMed1991

Comparisons of spontaneous pain and tenderness in patients with primary fibromyalgia.

Pain was assessed in 47 patients with fibromyalgia in the University Rheumatology Clinic in Basle with the aid of three different techniques. First, a simple visual analog scale was used, later a body diagram on which patients could indicate pain separately in different regions of the body (pain score) and, finally, dolorimetric measurements at 56 typical PFS tender points. After four weeks of therapy, pain was again scored by patients using these techniques. The changes in assessment were compared with the aid of Spearman correlation. Data recorded with the aid of the body diagram correlated better with dolorimetric findings than did the results obtained from a simple visual analog scale. The severity of the disease can be more objectively assessed using these three techniques than it can using only the visual analog scale. In particular, the pain score and dolorimetry make possible a clear assessment of the value of therapeutic regimens.

Female↗
PubMed1991

Transgenic oncogene mice. Tumor phenotype predicts genotype.

The hypothesis that oncogenes influence tumor phenotype was tested by examining slides from 607 mammary tumors from 407 transgenic mice bearing the ras, myc, and/or neu oncogenes. Most tumors (91%) had patterns (phenotypes) that could not be classified by Dunn's standard nomenclature. The nonstandard tumors were described as eosinophilic small cell (SC), basophilic large cell (LC), or pale intermediate cell (IC). The SC tumor was associated with ras, the LC was associated with myc, and the IC was associated with neu, with specificities more than .90 and sensitivities ranging from .99 to .48. Thus, the tumor phenotype could be used to predict which oncogene was present in the animal. The presence of myc in combination with either ras or neu resulted in the predominance of LC tumors and accelerated tumorigenesis. The combination of ras and neu resulted in a decreased tumor incidence. Thus, knowledge of the oncogenes that were present could be used to predict the natural history of the disease.

Animals↗
PubMed1989

Animal models of human disease. Pathology and molecular biology of spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes.

This present review focuses on spontaneous neoplasms occurring in transgenic mice carrying and expressing activated cellular oncogenes. The historical development of transgenic mice as in vivo disease models is briefly traced, followed by a brief description of the actual technology in such systems. Additional emphasis is placed on the concept of targeting activated cellular oncogenes to specific tissues in transgenic mice. Cumulative experience with activated (Vmyc, ras, and neu (erb-B2] oncogenes in transgenic mice is considered in detail, with particular attention paid to the observed pathology, as well as to the kinetics of disease occurrence. It is concluded that transgenic mice offer the interested investigator(s) an excellent prospective, in vivo model of oncogenesis.

Animals↗
PubMed1987

Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: synergistic action of oncogenes in vivo.

We have derived and mated separate strains of transgenic mice that carry either the v-Ha-ras or the c-myc gene driven by the mouse mammary tumor virus (MMTV) promoter/enhancer. Mice carrying the MMTV/v-Ha-ras transgene manifest two distinct disturbances of cell growth. The first, a benign hyperplasia of the Harderian lacrimal gland, is diffuse, involves the entire gland, and likely requires only the abnormal action of the v-Ha-ras gene. The second involves the focal development of malignancies of mammary, salivary, and lymphoid tissue and likely requires additional somatic events. When the MMTV/v-Ha-ras and MMTV/c-myc strains are crossed to yield hybrid mice, their joint action results in a dramatic and synergistic acceleration of tumor formation. Since these tumors arise stochastically and are apparently monoclonal in origin, additional somatic events appear necessary for their full malignant progression, even in the presence of activated v-Ha-ras and c-myc transgenes.

Adenocarcinoma↗