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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 397 records · Page 22Linked to original sources

Interleukin-4 transgenic mice of resistant background are susceptible to Leishmania major infection.

The outcome of cutaneous leishmaniasis is dependent on the balance of Th1 and Th2 cells. In the murine model, Th1 cells are host-protective whereas the Th2 cells are disease-promoting. However, the in vivo role of interleukin-4 (IL-4), a signature product of Th2 cells, is uncertain. We compared the course of Leishmania major infection in the genetically resistant 129/Sv mice and the mutant 129/Sv mice transgenic for the murine IL-4 gene under the control of the immunoglobulin heavy chain enhancer and promoter. We report here that in contrast to their wild-type parents, the IL-4 transgenic mice are susceptible to L. major infection. This is associated with the development of inexorably progressive lesions and parasite loads. Spleen cells from infected transgenic mice produced significantly higher levels of IL-4 but lower amounts of interferon-gamma when stimulated in vitro with leishmanial antigens compared to those from infected normal 129/Sv mice. Furthermore, sera from the infected transgenic mice contained higher levels of IL-4 and IgE than the sera of infected normal 129/Sv mice. These results, therefore, establish in a new animal model that IL-4 promotes disease development in murine cutaneous leishmaniasis.

Animals↗

pS2 protein in gastric carcinoma and normal gastric mucosa: association with clincopathological parameters and patient survival.

The presence of pS2 protein (pS2) was studied in a total of 120 consecutive patients with gastric carcinomas. This immunohistochemical study found pS2 expression in 48 per cent (n = 58) of carcinomas. pS2 expression was also detected in normal gastric mucosa in 95 per cent (n = 102) of specimens in upper antral mucopeptic glands and deep foveolar cells of the gastric pits but not in intestinal metaplasia. There was a significant statistical correlation between pS2 expression and extent of tumour growth (pT state) and expression of pepsinogen II by the tumours. There was no statistical correlation with clinical features such as patient age or sex or other pathological parameters (tumour stage, size, grade, and localization or growth pattern according to histological classification). There were no statistically significant differences in survival times between patients with pS2-positive and pS2-negative tumours. In contrast to findings concerning breast cancer, pS2 expression in gastric carcinomas had no influence on the patient's prognosis. On the other hand, strong expression of pS2 by surface epithelium of normal gastric mucosa may indicate that pS2 might play a role in physiological cell renewal of normal gastric mucosa.

Biomarkers, Tumor↗

Intraoperative diagnosis of retinal function.

During three-port vitrectomy, we stimulated local areas close to the macula with an intraocular glass fiberoptic. We were able to record a focal electroretinogram in 10 patients with severe diabetic retinopathy, which allowed a more precise evaluation of the retinal function correlated to the pathologic changes caused by the diabetic retinopathy.

Aged↗

Evaluation of knee ligament injuries with the IKDC form.

Various scoring systems have been proposed to quantify the disability caused by knee ligament injuries and to evaluate the results of treatment. None of these systems has found worldwide acceptance, mainly because all scoring systems attribute numerical values to factors that are not quantifiable, and then the arbitrary scores are added together for parameters not comparable with each other. For these reasons a group of knee surgeons from Europe and America met in 1987 and founded the International Knee Documentation Committee (IKDC). A common terminology and an evaluation form was created. This form is the standard form for all publications on results of treatment of knee ligament injuries. It is a concise one-page form. It includes a documentation section, a qualification section and a evaluation section. For evaluation there are four problem areas (subjective assessment, symptoms, range of motion and ligament examination). These are supplemented with four additional areas that are only documented but not included in the evaluation (compartmental findings, donor site pathology, X-ray findings and functional tests). The form can be used pre- and post-operatively and at follow-up. It has been specified that in any publication the minimum follow-up time for short-term results should be 2 years, for medium-term results 5 years and for long-term results 10 years. The largest part of the sheet is the qualification section. It is called "qualification" section rather than "scoring" section because no scores are given. Each parameter is qualified as "normal", "nearly normal", "abnormal" or "severely abnormal". This qualification is less subjective and emotional than "very good", "good", "fair" and "poor".(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

[Laparoscopic appendectomy as a routine procedure].

At the Gynaecology Department of the Bethesda Hospital, 100 patients undergoing a laparoscopic appendectomy were recruited for a prospective study. The first ten patients received no antibiotic, the second ten were given a three-day course of cephazolin, the third ten were treated with a combination of sulbactam and ampicillin and the remaining 70 received cefuroxime. There were no significant differences between the four groups in the mean operating time, the intraoperative complication rate or in the degree of inflammation as classified by the histological examination. The reduced rate of postoperative complications defined as pyrexia > 38 degrees C, elevated WBC and peritoneal irritation for more than two days, showed the advantage of antibiotic prophylaxis with cefuroxime with respect to single parameters and overall complication rates. There were no intraoperative or severe postoperative complications.

Adolescent↗

Liposomal amphotericin-B (AmBisome) for treatment of cutaneous widespread candidosis in an infant with methylmalonic acidaemia.

In a 10-week-old infant with vitamin B12-unresponsive methylmalonic acidaemia, cutaneous candidosis (Candida albicans) progressed rapidly despite topical antifungal treatment. After 1 week of intravenous therapy with liposomal amphotericin-B (AmBisome) the dermatitis disappeared completely and blood cultures were sterile. No side-effects were observed. This is one of the first experiences in the treatment of infants with this new antifungal agent.

Amino Acid Metabolism, Inborn Errors↗

Covariation of physiological sleep parameters in coronary patients and their relationships to sleep quality.

Relationships between the time series of five physiological sleep parameters were examined and related to sleep quality. Twenty-eight male coronary patients participated in the investigation. Recordings were carried out with a mobile device consisting of two Medilog 4-24 recorders and one DMI-recorder assessing five biosignals: EEG, EOG, EMG, ECG and body movements. Relationships between the time series of physiological sleep parameters were obtained by partitioning of covariance. The investigation showed that substantial relationships exist between the time series of the EEG, the number of eye movements and heart rate. Moreover, the time series of body movements showed substantial relationships to the time series of the EMG and heart rate. High correlations between the time series of the EEG and heart rate were related to a better sleep quality.

Adult↗

Interleukin-6 and acute-phase protein concentrations in surgical intensive care unit patients: diagnostic signs in nosocomial infection.

OBJECTIVE: To determine the value of serum concentrations of interleukin-6 (IL-6), C-reactive protein, and glycosylation of alpha 1-acid glycoprotein as tools for diagnosing nosocomial infection in surgical intensive care unit (ICU) patients. DESIGN: Prospective, consecutive entry study of patients with an anticipated stay of at least 24 hrs in a surgical ICU. SETTING: University hospital, a major provider of acute surgical care. PATIENTS: One hundred four consecutive patients admitted to the surgical ICU between March and June 1990. MEASUREMENTS: Concentrations of IL-6, C-reactive protein, and glycosylation of alpha 1-acid glycoprotein were measured on days 1 and 6 after ICU admission. Clinical evaluation for infection was performed daily in a blinded fashion, i.e., without knowing the results of the acute-phase parameters. MAIN RESULTS: On day 6 after surgery or trauma, nosocomial infection could be ascertained in 13 cases. The clinical parameter of fever > 38 degrees C had a sensitivity of 54% and a specificity of 90% to demonstrate nosocomial infection. Infected patients showed increased concentrations of IL-6 (p < .001), C-reactive protein (p < .001), and increased reactivity of alpha 1-acid glycoprotein to concanavalin A (p < .001) compared with patients without infections. By choosing appropriate cutoff values, IL-6 determinations had the highest specificity (97%), and C-reactive protein values had the highest sensitivity (85%) for diagnosing nosocomial infections. In uninfected patients, 81% of the IL-6 values, but only 29% of the C-reactive protein values, were back to the normal range on day 6 after injury. CONCLUSION: Due to the rapid normalization after trauma, a single measurement of the serum IL-6 concentration may be useful to support or refute the clinical suspicion of nosocomial infection.

Adolescent↗

An accessory gene, lipB, required for the production of active Pseudomonas glumae lipase.

Pseudomonas glumae PG1 is able to secrete lipase into the extracellular medium. The lipase is produced as a precursor protein, with an N-terminal signal sequence. A second open reading frame (ORF) was found immediately downstream of the lipase structural gene, lipA, a situation found for the lipases of some other Pseudomonas species. Inactivation of this ORF resulted in a lipase-negative phenotype, indicating its importance in the production of active extracellular lipase. The ORF, lipB, potentially encodes a protein of 353-amino-acid residues, having a hydrophobic N-terminal (amino acids 1 to 90) and a hydrophilic C-terminal part. As a first step in determining the role of LipB, its subcellular location was determined. The protein was found to fractionate with the inner membranes. The expression of fusions of lipB fragments with phoA revealed an N(in)-C(out) topology for the LipB protein, which was confirmed by protease accessibility studies on EDTA-permeabilized cells and on inverted inner membrane vesicles. These and other results indicate that most of the LipB polypeptide is located in the periplasm and anchored to the inner membrane by an N-terminal transmembrane helix, located between amino acids 19 and 40.

Amino Acid Sequence↗

Microheterogeneity of alpha 1 acid glycoprotein in rheumatoid arthritis: dependent on disease duration?

The microheterogeneity of alpha 1 acid glycoprotein (AGP) was studied using affinity immunoelectrophoresis with concanavalin A (Con A) in serum samples of 43 patients with early rheumatoid arthritis (RA) without clinical features of intercurrent infection. The results were expressed as reactivity coefficients. Disease activity was measured by clinical (Lansbury's joint index, Mallya-Mace activity score) and laboratory (erythrocyte sedimentation rate, levels of soluble interleukin-2 receptor, C reactive protein, and AGP) indices. In contrast with previous reports, suggesting a decrease in AGP-Con A reactivity in patients with RA, high values of AGP reactivity coefficients were found in patients with disease of short duration, which were similar to those found in patients with acute bacterial infections. Conversely, normal or decreased values of AGP reactivity coefficients were found in patients with disease of longer duration. Regression analysis showed a significant relation between AGP reactivity coefficients and disease duration (multiplicative model). No other indices examined were significantly related to disease duration. These results, taken together with previous findings suggesting that cytokines control the glycosylation of acute phase proteins, indicate that differences in the microheterogeneity of AGP in early and longstanding RA reflect differences in cytokine action at different stages of the disease.

Adolescent↗

Analysis of voltage-dependent membrane currents in spatially extended neurons from point-clamp data.

1. Numerical methods were used to evaluate voltage space-clamp performance in the investigation of a voltage-dependent inward current similar to the noninactivating Ca current. In addition, the cell is equipped with a repolarizing system, represented by leak and outwardly rectifying outward conductances. The electrotonically compact model cell is represented by a cable with an electrotonic length of 1 space constant under control conditions, but that becomes effectively only 0.33 space constants during a 90% reduction of the leak and outward conductance. The cable is perfectly voltage clamped at one end. 2. The apparent voltage dependence, activation, and inactivation of the clamp current depend on the distribution of the membrane slope conductance along the cable; this depends on 1) the distribution of the inward current along the cable and 2) the amplitude of the inward current relative to the amplitudes of the leak and voltage-dependent outward currents. 3. Under control conditions, the membrane voltage decays steeply with distance from the command voltage at the clamp site to almost resting potential for most of the rest of the cable. This is because the leak and outward current are dominant over the inward current. The inward current is activated primarily at the clamped part of the cable. Clamp currents are activated instantaneously. The clamp-current current-voltage (I-V) relation is less steep with depolarization because the membrane potential for locations away from the clamp site lags behind the clamp potential. 4. When the conductances for leak and outward current are reduced by 90%, these conductances lose their dominance. The membrane slope conductance now has a range with negative values.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Influence of Long-Term Stimulation on Pattern-Reversal Visual Evoked Cortical Potentials].

In 20 subjects, we recorded the pattern-reversal visual evoked cortical potential (VECP) over a period of 30 min. We could not find any remarkable alterations of the peak times, they were unchanged over the time. During the first 10 min, the amplitudes showed a clear tendency to decrease if one evaluated the averaging value of the whole group. After this time, there were no significant changes. But we learned a quite different behavior of amplitudes evaluating the record of each subject. We found 5 types of different behavioral modulated responses. The problems of long-term investigation are sophisticated and need further investigation to learn which different factors have an impact on VECP. From a clinical point of view, a long-term investigation shows no relevant potential alterations.

Adult↗

Clinical and molecular analysis of five inv dup(15) patients.

Five patients with inv dup(15) chromosomes were investigated with molecular probes on proximal 15q to determine the parental origin and extent of the duplicated segment. Cytogenetic investigation showed that four patients carried one and a fifth patient had two extra chromosomes derived from number 15 in all cells. In situ hybridization with a chromosome 15 library and a centromere 15 probe confirmed that the entire inv dup chromosomes were derived from chromosome 15. Molecular analysis using probes mapping in the region deleted in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients implied that in at least two patients the extra chromosomes were asymmetric with one copy of the PWS region on the extra marker chromosome but two copies of the region centromeric to the PWS region. Three other cases had an inv dup(15) with two extra copies of the PWS region, but in one of these, heteromorphisms clearly demonstrated that the two centromeres derived from two different chromosomes. The inv dup(15) presumably resulted from an illegitimate recombination event between two different chromosomes 15 in most or all of these cases. All patients showed a maternal origin of the duplicated chromosome. The clinical severity appears to be associated with dosage of the PWS/AS region rather than with differences in the extent of the duplicated segment.

Abnormalities, Multiple↗

Evaluation of mutagenicity testing with Salmonella typhimurium TA102 in three different laboratories.

Thirty compounds of various chemical classes were investigated for mutagenicity in a collaborative study (three laboratories) using Salmonella typhimurium TA102. With five compounds, hydrazine sulfate, phenylhydrazine, hydralazine, glutardialdehyde, and glyoxal, mutagenicity was detected by all laboratories. Formaldehyde was assessed as weakly mutagenic in only one of three laboratories. The remaining 24 agents were uniformly described as non-genotoxic in TA102. In spite of the overall good qualitative agreement in the mutagenicity results between the three laboratories, some quantitative discrepancies occurred in the dose response of the mutagenic compounds. Varying inter- and intralaboratory differences in the spontaneous rate of revertants were obtained. The usefulness of the tester strain TA102 in routine mutagenicity testing is discussed.

Formaldehyde↗

Glycosylation of acute phase proteins and interleukins following hip arthroplasty. Inflammation parameters studied in 10 patients.

We analyzed changes in glycosylation and serum concentrations of alpha 1-acid glycoprotein (AGP), antichymotrypsin (AC), interleukin-6 (IL-6), soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) following hip arthroplasty. Glycosylation of AGP and AC showed an increased reactivity to concanavalin A between postoperative Day 2 and Day 5 and Day 10, respectively. Serum levels of AGP and AC increased at the earliest on Day 5. The AC levels returned to baseline by Day 10. AGP, however, exhibited increased values beyond Day 14. CRP levels were elevated at Day 2 and remained increased beyond Day 14. sIL2R showed increased values at Days 5, 10 and 14. IL-6 was the first parameter to increase, and it returned to baseline in less than 5 days.

Acute-Phase Proteins↗

A special high tibial osteotomy technique for treatment of unicompartmental osteoarthritis of the knee.

Tibial osteotomy is a well-established procedure for treatment of the varus osteoarthritic knee. A special new technique of oblique tibial osteotomy at the level of the tibial tubercle, preserving the medical cortex and iliotibial band, is presented which allows partial weight bearing the first postoperative day. Postoperatively the femorotibial alignment should be 5 degrees to 7 degrees of valgus in elderly patients. Because in younger individuals the intact iliotibial band is a strong restraint against varus deformity, we seek to correct to 3 degrees to 5 degrees of valgus in these patients. Of 172 cases treated with this technique between 1982 and 1986, 50 patients were retrospectively reviewed. After a follow-up period of 6 months to 3 years, pain was relieved in 46 patients. Complications consisted of 5 secondary wound healings, including 2 superficial infections, 1 tibial plateau fracture, and 3 varus recurrences.

Adolescent↗