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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 55 records · Page 3Linked to original sources

Protein A immunoadsorption in a pregnant woman with habitual abortion.

The role of antibodies in the occurrence of recurrent spontaneous miscarriage is well known. However there are many controversial issues in the management of habitual abortion. This paper describes the effect of Protein A immunoadsorption on serum levels of these antibodies and its impact on a case of a successfully treated woman in a outpatient department without need for a central venous catheter. Given the favourable clinical results described in our paper we think it may be relevant for some worse cases in clinical practice and will interest your readers.

Abortion, Habitual↗

Stable and long-lasting immune response in horses after DNA vaccination against equine arteritis virus.

Equine arteritis virus (EAV) is the causative agent of the equine viral arteritis. It is a small RNA virus with a linear, non-segmented plus RNA genome. EAV is a member of the Arteriviridae family that includes porcine reproductive and respiratory syndrome virus (PRSSV), simian haemorrhagic fever virus (SHFV) and lactate dehydrogenase virus (LDV). The viral transmission is via respiratory and reproductive routes. Clinical signs in horses vary, and severe infection can lead to abortions in pregnant mares or neonatal foal death. The aim of this study was to investigate the development of the immune response in horses after immunization with a DNA vaccine harbouring and expressing EAV Open Reading Frames (ORF) 2, 5, and 7, in combination with equine interleukin 2 (eqIL2). Three boosters followed the basic immunization in two-week intervals. Each immunization was a combination of gene gun and intramuscular injection. All horses developed a high titer of neutralizing antibodies after basic immunization within 2 weeks. Remarkably, this immune response was found to be independent of the age of animals. The youngest horse was six-years old, and the oldest twenty-two years old. A remarkable difference in the immune response between the young and old were not observed. The duration of immunity was investigated during a period of one year. After 12 months, neutralizing antibodies were still detectable in all the vaccinated horses.

Animals↗

Sequence analysis of the full-length cloned DNA of a chicken anaemia virus (CAV) strain from Bangladesh: evidence for genetic grouping of CAV strains based on the deduced VP1 amino acid sequences.

Chicken anaemia virus (CAV) was detected in the bursa of Fabricius of a 4-week-old chicken obtained from an outbreak of acute infectious bursal disease in Bangladesh. Repeated attempts to grow this virus in MDCC-MSB1 cells were not successful. A full-length PCR amplicon of the genome of this strain, designated as BD-3 CAV, was cloned and sequenced. The complete nucleotide sequence and the deduced amino acid sequence were compared with those of 12 other CAV strains. The genetic analysis of the amino acid sequences of VP1 indicated the possible existence of genetic groups among CAV strains, as BD-3 CAV along with four other strains (CIA-1, L-028, Isolate 704 and TR-20) formed a distinct lineage. These strains have four signatory amino acids in VP1, such as 75I/T, 97L, 139Q and 144Q, out of which the latter two are located in a small hydrophilic peak.

Amino Acid Sequence↗

Combined regional and systemic chemotherapy for advanced and inoperable non-small cell lung cancer.

AIMS: The objective was to establish the feasibility and toxicity of regional chemotherapy using an isolated thoracic perfusion (ITP) technique plus low dose systemic chemotherapy as induction chemotherapy followed by surgery in advanced non-small cell lung cancer (NSCLC). METHODS: twenty-two chemotherapy-naive patients with NSCLC (median age of 57 years, stage III-IV disease with metastases only in the thoracic region, Karnofsky index >60), received two cycles of regional plus systemic chemotherapy with a treatment-free interval of 4 weeks. The cytostatic regimen consisted of 10 mg/m(2) mitomycin, 25 mg/m(2) navelbine and 30 mg/m(2) cisplatin during ITP followed by low-dose systemic chemotherapy with 250 mg/m(2) 5-fluorouracil and 20 mg/m(2) cisplatin given as a continuous infusion on day 1-4. Patients were re-evaluated for response and surgery was carried out if possible. RESULTS: All 22 patients could be assessed for toxicity, response and survival. There were 19/22 remissions corresponding to a regression rate of 86.4%; 16/22 patients could be resected. This corresponded to a resectability rate of 72.7% (13 complete resections R0, 1 R1, 2 R2). Side-effects were transient and acceptable with no treatment- or surgery-related deaths. Median survival has not been reached after an observation time of 15 months. The estimated 1-year survival rate was 67.3%. CONCLUSIONS: Regional chemotherapy using an ITP application form is highly effective in advanced NSCLC stage III-IV leading to a high rate of resectability with an encouraging survival outcome.

Adult↗

[Problems encountered during the installation of an automated anesthesia documentation system (AIMS)].

Problems encountered during the installation and introduction of an automated anaesthesia documentation system are discussed. Difficulties have to be expected in the area of staff training because of heterogeneous experience in computer usage and in the field of online documentation of vital signs. Moreover the areas of net administration and hardware configuration as well as general administrative issues also represent possible sources of drawbacks. System administration and reliable support provided by personnel of the department of anaesthesiology assuring staff motivation and reducing time of system failures require adequately staffed departments. Based on our own experiences, we recommend that anaesthesiology departments considering the future installation and use of an automated anaesthesia documentation system should verify sufficient personnel capacities prior to their decision.

Anesthesia Department, Hospital↗

Intraepithelial high-grade neoplasia and early adenocarcinoma in short-segment Barrett's esophagus (SSBE): curative treatment using local endoscopic treatment techniques.

BACKGROUND AND STUDY AIMS: In recent years, short-segment Barrett's esophagus (SSBE) has attracted increasing attention in the context of reflux disease. However, there is continuing controversy regarding its potential for malignant transformation. PATIENTS AND METHODS: Between October 1996 and September 1999, 50/115 patients (43 %) with intraepithelial high-grade neoplasia or early Barrett's adenocarcinoma, who underwent local endoscopic treatment, had developed a malignant lesion in an (SSBE). In the framework of a prospective observational study, 28 patients were treated with endoscopic mucosal resection (EMR), 13 with photodynamic therapy, and three with argon plasma coagulation; six patients received combinations of these treatments. RESULTS: Complete local remission was achieved in 48/49 patients (98 %). One patient switched to surgery after the first EMR, because there was submucosal tumor infiltration, and in one patient out of 50 local endoscopic treatment failed. A mean of 1.7 +/- 1.4 treatment sessions was required for local endoscopic treatment. The method-associated mortality was 0 %. The rate of relevant complications (stenosis, bleeding) was 6 % (3/50 patients). No cases of severe hemorrhage (Hb fall >2 g/dl) or perforation occurred. During a mean follow-up period of 34 +/- 10 months, metachronous intraepithelial high-grade neoplasms or early adenocarcinomas were seen in 11/48 patients (23 %), who received further successful endoscopic treatment. Four patients died during the follow-up period, but in only one patient was this due to his Barrett's adenocarcinoma (this was the patient who underwent esophageal resection). CONCLUSIONS: The malignant potential of short-segment Barrett's esophagus must not be underestimated. Organ-preserving local endoscopic treatment shows good acute-phase and long-term results. Local endoscopic treatment represents an alternative to esophageal resection in the case of intraepithelial high-grade neoplasia and selected early adenocarcinomas in Barrett's esophagus.

Adenocarcinoma↗

Can the diagnosis of NSAID-induced or Hp-associated gastric ulceration be predicted from histology?

We studied the question whether NSAID/ASA-induced ulcerations can be identified in human gastric biopsy material on the basis of ischaemic necrosis. Biopsies of 208 patients with gastric ulcers were assessed histologically. 29 patients were excluded from the study. NSAID/ASA ulcers were diagnosed when a homogeneous eosinophilic ischaemic necrosis was found. Helicobacter pylori-(Hp-) induced ulcers were diagnosed when non-homogeneous fibrinoid necrotic material containing granulocytes and cell debris was noted. The histological diagnosis was compared with the data on medication use, endoscopy and clinical history. 121 of the 179 patients included had a medical history on NSAIDS/ASA. From the 60 patients taking NSAIDS/ASA with no histologic evidence of Hp all (100 %) were identified by the histology of the necrosis. From the 61 patients taking NSAID/ASA and histologic evidence of H. pylori 40 (66 %) were identified by histology. From the 58 patients with no such medication 41 were Hp-positive and correctly identified by histology in 31 cases (76 %). The sensitivity of the histologic diagnosis of NSAID/ASA-induced ulceration was 85 %, and its specificity 53 %. The results of our study show that a high percentage of the NSAID/ASA-induced ulcers of the stomach can indeed be correctly diagnosed at histology. In conclusion the underlying aetiopathogenesis of gastric ulcerations (NASID/ASA vs. Hp) can be uncovered in a large proportion of patients based on histological examination.

Aged↗

Lake Constance--a model for integrated lake restoration with international cooperation.

Lake Constance is the second largest prealpine European lake. Its international catchment area lies in the territories of the four European countries Austria, Germany, Liechtenstein and Switzerland. Since the fifties, a significant degradation of its state was observed as a result of the pollutants of more than 1.2 million inhabitants in its catchment area. To counteract this negative development, international cooperation was realized in the International Commission for the Protection of Lake Constance (IGKB). Thereby the phosphorus concentration in the lake water, after a maximum value of 87 mg/m3 phosphorus in 1979, was reduced to 13 mg/m3 until 2001. To prevent the negative effects of unfavourable climatic conditions resulting in an incomplete vertical circulation, the concentration of phosphorus must be reduced to 10 mg/m3. Crucial points in future are to sustain the present successes in lake protection, to reduce existing loads as much as possible, to compensate for loads which are not avoidable and to avoid future loads. A sustainable use of the lake is ensured only by an intact lake ecosystem.

Agriculture↗

Tests of relativity using a cryogenic optical resonator.

A 190-day comparison of the optical frequencies defined by an optical cavity and a molecular electronic transition is analyzed for the velocity independence of the speed of light (Kennedy-Thorndike test) and the universality of the gravitational redshift. The modulation of the laboratory velocity and the gravitational potential were provided by Earth's orbital motion around the Sun. We find a velocity-dependence coefficient of (1.9+/-2.1)x10(-5), 3 times lower compared to the best previous test. Alternatively, the data confirm the gravitational redshift for an electronic transition at the 4% level. Prospects for significant improvements of the tests are discussed.

Journal Article↗

Nontruncating APC germ-line mutations and mismatch repair deficiency play a minor role in APC mutation-negative polyposis.

Familial adenomatous polyposis, an autosomal-dominantly inherited colorectal cancer predisposition syndrome, is caused by germ-line mutations in the adenomatous polyposis coli (APC) gene. Despite the use of different screening methods, studies worldwide fail to identify APC mutations in 20-50% of all familial adenomatous polyposis patients (APC mutation-negatives). In this study, missense mutations in the coding region of the APC gene, which would have been missed by the protein truncation test, as well as mutations in the APC promoter and the 3' untranslated region, were determined by the single nucleotide polymorphism discovery assay and direct DNA sequencing in 31 mutation-negative polyposis patients. Seventeen gene alterations were identified, whereof four (12.9%) represent possibly pathogenic germ-line mutations: silent A290T (promoter) and A8822G (3' untranslated region) as well as missense R99W and E1317Q (coding region). The 27 remaining, truly APC mutation-negative polyposis patients displayed a significantly later age at diagnosis compared with APC mutation carriers (46.1 versus 35.2 years; P < 0.01). APC mutation-negative individuals with >100 colonic polyps were more likely to present with extracolonic disease (P < 0.05) than those with <100. Assessment of microsatellite instability (MSI), a hallmark of mismatch repair deficiency, in 68 tumors from 21 truly APC mutation-negative patients, identified 4 (5.9%) unstable tubulo-villous adenomas (3 MSI-High and 1 MSI-Low), stemming from 4 (19%) unrelated individuals and likely to be caused by hMLH1 promoter hypermethylation. In conclusion, only a small proportion of APC germ-line mutation carriers is missed by the protein truncation test, and mismatch repair deficiency does not seem to substantially contribute to tumor development in APC mutation-negative polyposis patients.

3' Untranslated Regions↗

Zn(2+) binding to the cytoplasmic side of Paracoccus denitrificans cytochrome c oxidase selectively uncouples electron transfer and proton translocation.

Using a combination of stopped-flow spectrophotometric proton pumping measurements and time-resolved potential measurements on black lipid membranes, we have investigated the effect of Zn(2+) ions on the proton transfer properties of Paracoccus denitrificans cytochrome c oxidase. When zinc was enclosed in the interior of cytochrome c oxidase containing liposomes, the H/e stoichiometry was found to gradually decrease with increasing Zn(2+) concentration. Half-inhibition of proton pumping was observed at [Zn(2+)](i)=75 microM corresponding to about 5-6 Zn(2+) ions per oxidase molecule. In addition, there was a significant increase in the respiratory control ratio of the proteoliposomes upon incorporation of Zn(2+). Time-resolved potential measurements on a black lipid membrane showed that the electrogenic phases slowed down in the presence of Zn(2+) correspond to phases that have been attributed to proton uptake from the cytoplasmic side and to proton pumping. We conclude that Zn(2+) ions bind close to or within the two proton transfer pathways of the bacterial cytochrome c oxidase.

Binding Sites↗

Simultaneous immunohistochemical detection of tumor cells in lymph nodes and bone marrow aspirates in breast cancer and its correlation with other prognostic factors.

PURPOSE: We studied the prognostic and predictive value of immunohistochemically detected occult tumor cells (OTCs) in lymph nodes and bone marrow aspirates obtained from node-negative breast cancer patients. All were classified as distant metastases-free using conventional staging methods. PATIENTS AND METHODS: A total of 484 patients with pT1-2N0M0 breast cancer and 70 with pT1-2N1M0 breast cancer and a single affected lymph node participated in our trial. Ipsilateral axillary lymph nodes and intraoperatively aspirated bone marrow were examined. All samples were examined for OTCs using monoclonal antibodies to cytokeratins 8, 18, 19. Immunohistological findings were correlated with other prognostic factors. The mean follow-up was 54 +/- 24 months. RESULTS: OTCs were detected in 180 (37.2%) of 484 pT1-2N0M0 patients: in the bone marrow of 126 patients (26.0%), in the lymph nodes of 31 patients (6.4%), and in bone marrow and lymph nodes of 23 (4.8%) patients. Of the 70 patients with pT1-2N1MO breast cancer and a single involved lymph node, OTCs were identified in the bone marrow of 26 (37.1%). The ability to detect tumor cells increased with the following tumor features: larger size, poor differentiation, and higher proliferation. Tumors of patients with OTCs more frequently demonstrated lymph node invasion, blood vessel invasion, higher urokinase-type plasminogen activator levels, and increased PAI-1 concentrations. Patients with detected OTCs showed reduced disease-free survival (DFS) and overall survival (OAS) rates that were comparable to those observed in patients who had one positive lymph node. Multivariate analysis of prognostic factors revealed that OTCs, histological grading, and tumor size are significant predictors of DFS; OTCs and grading of OAS. CONCLUSION: OTCs detected by simultaneous immunohistochemical analysis of axillary lymph nodes and bone marrow demonstrate independent metastatic pathways. Although OTCs were significantly more frequent in patients with other unfavorable prognostic factors, they were confirmed as an independent prognostic factor for pT1-2N0M0, R0 breast cancer patients.

Adult↗

E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis.

The retinoblastoma protein (pRB) and its two relatives, p107 and p130, regulate development and cell proliferation in part by inhibiting the activity of E2F-regulated promoters. We have used high-density oligonucleotide arrays to identify genes in which expression changed in response to activation of E2F1, E2F2, and E2F3. We show that the E2Fs control the expression of several genes that are involved in cell proliferation. We also show that the E2Fs regulate a number of genes involved in apoptosis, differentiation, and development. These results provide possible genetic explanations to the variety of phenotypes observed as a consequence of a deregulated pRB/E2F pathway.

Apoptosis↗

Prognostic and predictive significance of ErbB-2 breast tumor levels measured by enzyme immunoassay.

PURPOSE: A retrospective analysis to assess the prognostic and predictive clinical value of breast tumor ErbB-2 receptor expression quantified by enzyme immunoassay (EIA), to compare levels measured by EIA with ErbB-2 status determined by immunohistochemistry (IHC), and to correlate receptor content with levels of phosphorylated (Y1248-P) ErbB-2, a measure of functional tyrosine kinase activity. MATERIALS AND METHODS: EIA quantification of ErbB-2 was performed on membrane extracts from 3,208 well-characterized primary breast cancers. Overall, relapse-free, distant disease-free, and local/regional-free patient survival data were available on 1,123 of these tumors. IHC scoring for ErbB-2 status (HercepTest; DAKO, Glostrup, Denmark) was performed on adjacent sections of 151 cases, and receptor functionality was measured in 230 tumors by an antibody specific for phosphorylated (Y1248-P) ErbB-2. RESULTS: Unlike nonmalignant breast tissues, breast tumors showed increased ErbB-2 levels in a bimodal distribution, with 12% constituting a distinct set of ErbB-2-overexpressing tumors. The intermodal threshold value for ErbB-2 overexpression distinguished tumors with reduced estrogen and progesterone receptor content, high IHC score for ErbB-2, and significantly increased levels of phosphorylated (Y1248-P) ErbB-2 receptor. By multivariate analysis, EIA-determined ErbB-2 overexpression predicted significantly reduced patient survival that was unaffected by tamoxifen or cyclophosphamide, methotrexate, and fluorouracil adjuvant therapy. CONCLUSION: Determination of ErbB-2 receptor expression by EIA offers a clinically valuable alternative to semiquantitative IHC assessment of breast tumor ErbB-2 overexpression and affords the opportunity to evaluate ErbB-2 phosphorylation, which may represent an important predictive parameter of receptor functionality.

Adult↗

Antifungal actinomycete metabolites discovered in a differential cell-based screening using a recombinant TOPO1 deletion mutant strain.

In the course of a natural product screening for inhibitors of fungal topoisomerase 1 (TOPO 1), extracts from the actinomycete strains WS 1410 and BS 1465 exhibited promising activities. Bioguided fractionation of the culture broth by preparative HPLC methods yielded the collismycins A (1) and B (2) as active principles of strain WS 1410. Out of the mycelial extracts of strain BS 1465 the bioactive new natural products, cyclo-homononactic acid (3) and cyclo-nonactic acid (5) and the structurally related but inactive homononactic acid (4), were isolated. Both collismycin isomers inhibited the recombinant yeast strains ScAL 141 and ScAL 143 (TOPO 1 deletion mutant) in a non-specific manner with an MIC in the range of 2 micrograms/ml. The novel cyclo-homononactic acid (3) and cyclo-nonactic acid (5) showed higher selectivity towards the wild type strain (MIC = 2 micrograms/ml as compared to 10 micrograms/ml for the deletion mutant). All compounds obviously address a target other than TOPO 1 since they do not exhibit activities in a concurrent TOPO 1 enzyme assay.

2,2'-Dipyridyl↗

[A hospital suited version of the German SF-36 and its psychometric comparison with the original questionnaire].

OBJECTIVES: The application of the Short-Form 36 Health Survey (SF-36) in hospitals is sometimes problematic, because some formulations like "at work" or "at home" in some items are not adequate in a hospital context. To account for this problem, we deleted 23 words like "at work" and "at home" from the SF-36 and generated thus a slightly modified version, the SF-36 m. The present paper deals primarily with two questions: is the SF-36 m well applicable in hospitals and is it still equivalent with the original version? METHODS: The SF-36 m was applied in more than 300 patients in two different hospitals. In one hospital a randomised design was used to assess the equivalence of SF-36 and SF-36 m before treatment. RESULTS: The reported high percentages of missing values in four critical scales were no more observed, when the SF-36 m was applied at the end of hospital stays. Only minor differences between SF-36 and SF-36 m with effect sizes < 0.20 were observed, although the scale "physical role function" and especially item 4d showed unexpectedly significantly higher values in the SF-36 m (p < 0.10). Additionally, higher and significant differences were observed between the applications of the questionnaires at home and in the hospital. CONCLUSIONS: Opposed to the original SF-36 the SF-36 m is well applicable at the end of hospital stays. SF-36 and SF-36 m show only minor differences in the comparison of their equivalence. The application of SF-36 and SF-36 m in hospitals seems to yield more favourable scores of health related quality of life than the application at home.

Chronic Disease↗

[Lymphocytic gastritis--a rare disorder of the gastric mucosa].

Lymphocytic gastritis, first described by Haot et al. in 1986, is a very rare form of gastritis (0.8-1.6% of cases) with unclear pathogenesis. On endoscopy, lymphocytic gastritis may present either a normal appearance, such as gastritis varioliformis with multiple elevated chronic erosions in the corpus and fundus, or as a giant fold gastritis in the corpus and fundus. This type of gastritis is diagnosed histologically based on an accumulation of intraepithelial lymphocytes (more than 25/100 epithelial cells) in the surface cells of the gastric mucosa. Its etiopathogenesis is currently thought to be a sprue-associated reaction or an atypical reaction to Helicobacter pylori infection. Some studies report the lymphocytic gastritis in almost 45% of cases of sprue, with the gastritis regressing in response to a gluten-free diet, while others report a correlation of lymphocytic gastritis with serologically and/or histologically confirmed H. pylori infection, with the lymphocytic gastritis being cured by H. pylori eradication treatment in a high percentage of the cases. It is possible that a similar abnormal immune reaction to an inflammatory agent underlies both pathological entities, sprue and lymphocytic gastritis--in the one case gluten and in the other H. pylori--which would mean that sprue-induced and H. pylori-induced forms of lymphocytic gastritis exist side by side.

Celiac Disease↗