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Biomedical subjects

W Müller

Publications and source records attributed to W Müller.

At least 307 records · Page 17Linked to original sources
PubMed1996

Considerations on the tendency for calcification in meningiomas.

Calcifications in meningotheliomatous and fibromatous meningiomas were demonstrated after maceration under the scanning electron microscope and by pluck preparation. In five predominantly meningotheliomatous and five fibromatous meningiomas vascular features were studied after injection of Indian ink. The influx of calcium into the tumor parenchyma is thought to be related to long vessel loops and parallel coursing vessels which act as a countercurrent multiplication system similar to the loops of Henle in the kidney. Abruptly changing of diameter of vessels reduces the flow rate and enhances the transport of ions across vessels walls. Furthermore, the fine structure of endothelium favors the escape of ions into vessel walls and into parenchyma. Possible consequences of an intratumoral Ca overload are briefly discussed.

Calcinosis↗
PubMed1995

Pituitary adenylate cyclase-activating polypeptide stimulates cardiodilatin/atrial natriuretic peptide (CDD/ANP-(99-126) secretion from cultured neonatal rat myocardiocytes.

It has been reported that the highly homologous neuropeptides pituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP) exert similar cardiovascular effects in vivo. In the present study we compared the effects of these neuropeptides on myocardial cyclic AMP content and the release of immunoreactive CDD/ANP-(99-126) (atrial natriuretic peptide). In cultured neonatal rat cardiomyocytes PACAP and VIP evoke concentration-dependent increases in intracellular cyclic AMP content but responses to VIP are markedly less. PACAP stimulates the release of CDD/ ANP-(99-126) in a concentration-dependent manner with a threshold concentration of 1 nM, and up to a 6-fold increase in basal secretion at 1 microM PACAP. In contrast. VIP had no effect on the release of CDD/ANP. Pretreatment of cells with the competitive PACAP-antagonist, PACAP-6-38 (1 microM), significantly reduces the effects of PACAP on intracellular cyclic AMP and on CDD/ANP-(99-126) secretion and abolishes the effects of VIP on cyclic AMP. Pretreatment with VIP-receptor antagonist (1 microM) prevents the cyclic AMP-response to VIP while increases in cyclic AMP as well as stimulation of CDD/ANP-(99-126) release by PACAP are not affected. It is concluded that both neuropeptides directly influence cardiac myocytes through an increase in intracellular cyclic AMP. Release of CDD/ ANP-(99-126) by PACAP may be involved in the decrease in blood pressure that follows intravenous administration of this peptide. The higher potency of PACAP to induce cyclic AMP synthesis, its stimulating effect on the release of CDD/ANP-(99-126) and the finding that the VIP-receptor antagonist inhibits responses to VIP but not to PACAP suggest that PACAP activates cardiac myocytes through a PACAP-specific receptor.

Animals↗
PubMed1995

4-4-20 anti-fluorescyl IgG Fab' recognition of membrane bound hapten: direct evidence for the role of protein and interfacial structure.

The surface forces apparatus was used to identify the molecular forces that control the interactions of monoclonal 4-4-20 antifluorescyl IgG Fab' fragments with fluorescein-presenting supported planar bilayers. At long range, the electrostatic force between oriented Fab' and fluorescein monolayers was controlled by the composition of the protein exterior surrounding the antigen-combining site rather than by the overall protein charge. The measured positive electrostatic potential of the Fab' monolayer at pH > pI(Fab') was consistent with the structure of the exposed Fab' surface in which a ring of positive charge at the mouth of the antigen-combining site dominates the local electrostatic surface properties. Substantial differences in the electrostatic forces measured with denatured Fab' further demonstrated that the measured electrostatic surface properties and the consequent long-range interaction forces are controlled by the protein surface composition. At short range, the strength of the Fab'-mediated adhesion was modulated not only by the length of the fluorescein tether but also by membrane hydration. Steric hydration barriers at the membrane surface reduced the adhesion strength in proportion to their range of influence. These results provide direct evidence that long-range protein interactions with immobilized ligands are controlled by both the protein and the membrane surface compositions, while short-range, specific binding is modulated by both the protein structure and the membrane interfacial properties.

Antibodies, Monoclonal↗
PubMed1995

The relationship of p53 expression to the prognosis of 418 patients with gastric carcinoma.

BACKGROUND: Mutations of the p53 gene belong to the most common genetic alterations in human cancer that have been implicated in tumorigenesis and tumor progression. Although p53 expression appears to be correlated with prognosis in patients with breast cancer and some other types of cancer, its prognostic role in gastric cancer is still uncertain. In the present study, therefore, the prognostic impact of p53 expression was evaluated in 418 patients with curatively resected gastric carcinomas without residual tumor (RO-resection). METHODS: Tumor sections of 418 RO-resected gastric carcinomas were stained with the monoclonal antibody DO-1 after microwave processing. p53 expression was statistically compared with clinico-pathologic features and postoperative survival. RESULTS: p53 expression was detected in 57.5% of all tumors, with strong inter- and intratumor heterogeneity. No immunoreactivity was observed in the normal mucosa adjacent to the tumor. Statistically, no significant correlation between p53 overexpression and depth of invasion, lymph node involvement, or grade of tumor differentiation was detected. The correlations with blood vessel invasion (P = 0.049) and lymphatic vessel invasion (P = 0.047) were of marginal significance. Survival analysis revealed no significant impact of p53 expression on survival, the 5-year survival rates were 40.6% +/- 7.8% for patients with p53 positive tumors and 49.2% +/- 8.9% for patients with p53 negative tumors (P = 0.43). Furthermore, no correlation with survival was found when four different levels of p53 expression were analyzed (P = 0.51). p53 expression had no influence on survival, in either the lymph node positive or negative groups. CONCLUSIONS: The data suggest that the immunohistochemical detection of p53 expression is at present not a predictor of outcome of patients with gastric cancer or to identify subgroups of patients who may be at higher risk.

Adult↗
PubMed1995

A role for CD5 in TCR-mediated signal transduction and thymocyte selection.

CD5 is a transmembrane protein that is expressed on the surface of T cells and a subset of B cells. The absence of CD5 rendered thymocytes hyperresponsive to stimulation through the T cell antigen receptor (TCR) in vitro. Selection of T cells expressing three distinct transgenic TCRs was also abnormal in CD5-deficient mice. These observations indicate that CD5 can influence the fate of developing thymocytes by acting as a negative regulator of TCR-mediated signal transduction.

Animals↗
PubMed1995

Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses.

We have examined the role of endogenously produced interleukin (IL) 4 and IL-10 in the regulation of inflammatory and immune reactions in the skin. In these experiments, irritant and contact hypersensitivity (CH) responses were elicited in mice with targeted disruptions of the IL-4 (IL-4T) or IL-10 (IL-10T) gene. Our study showed that IL-4T and wild-type (wt) mice exhibited equivalent responses to the irritant croton oil. In contrast, the response of IL-10T mice challenged with croton oil was abnormally increased. When IL-10T mice were exposed to a higher dose of irritant, irreversible tissue damage occurred. By comparison, any treatment of wt mice with croton oil resulted in far less tissue damage and resolution of inflammation. Neutralizing antibody studies demonstrated that the necrosis that occurred in IL-10T mice was due to the overproduction of tumor necrosis factor. The anti-tumor necrosis factor antibody treatment of IL-10T mice did not significantly reduce the edema or the influx of inflammatory cells, suggesting that these changes were due to the uncontrolled production of other proinflammatory cytokines. T cell-dependent immune responses were also evaluated using the contact sensitizer oxazolone. The response of IL-4T mice did not differ from wt mice. In contrast, IL-10T mice mounted an exaggerated CH response, increased in both magnitude and duration as compared with wt mice. Based on these studies, we have concluded that IL-10, but not IL-4, is a natural suppressant of irritant responses and of CH, and it limits immunopathologic damage in the skin.

Animals↗
PubMed1995

Mouse anti-mouse IgD monoclonal antibodies generated in IgD-deficient mice.

The production of high-affinity monoclonal antibodies (mABs) is generally restricted to antigens recognised as foreign by the immune system. Here we report the generation of mouse mABs specific for mouse IgD. Mice rendered IgD-deficient by gene targeting and consequently immunologically fully responsive to mouse IgD, were used to elicit a humoral response against mouse IgD. Hybridomas producing mABs of high affinity were isolated and clones specific for non-allotypic determinants on the Fc or Fab portion of mouse IgD were obtained. The data show that mice lacking a protein of interest due to targeted gene inactivation can be utilised for the production of high-affinity mABs specific for that mouse protein and should also facilitate the generation of mABs specific for proteins highly conserved between species.

Animals↗
PubMed1995

Activation of Ca2+ signaling in neutrophils by the mast cell-released immunophilin FKBP12.

The immunophilins of the FK506-binding protein (FKBP) family are intracellular proteins that bind the immunosuppresants FK506 and rapamycin. In this study we show that HMC-1 mast cells sensitized with IgE release FKBP12 upon stimulation with anti-IgE. The release is rapid and not affected by actinomycin D or cycloheximide, suggesting that it is due to exocytosis from a storage compartment. FKBP12 from HMC-1 mast cells exhibits biological activity. When applied extracellularly to human neutrophils, it induces transient changes in the intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ release from intracellular stores. Inhibition of [Ca2+]i changes by ruthenium red and ryanodine indicates that ryanodine receptor/Ca2+ release channels are involved in FKBP12-induced Ca2+ signaling. Neutrophil activation by mast cell-derived FKBP12 is prevented by complexing FKBP12 with FK506 or rapamycin. These results demonstrate that extracellular FKBP12 functions as a cytokine in cell-to-cell communication. They further suggest a pathophysiological role for FKBP12 as a mediator in immediate or type I hypersensitivity and may have implications for novel therapeutic strategies in the treatment of allergic disorders with FK506 and rapamycin.

Amino Acid Sequence↗
PubMed1995

Lymphoid development in mice with a targeted deletion of the interleukin 2 receptor gamma chain.

The interleukin 2 receptor gamma chain (IL-2R gamma) is a component of the receptors for IL-2, IL-4, IL-7, and IL-15. Mutations in IL-2R gamma in man appear responsible for the X chromosome-linked immunodeficiency SCIDX1, characterized by a defect in T-cell and natural killer (NK)-cell differentiation with the presence of poorly functioning B cells. To explore at which level IL-2R gamma affects lymphoid development in vivo, we have analyzed mice derived from embryonic stem (ES) cells with mutant IL-2R gamma loci generated by Cre/loxP-mediated recombination. In the peripheral blood of chimeric animals, lymphoid cells derived from IL-2R gamma- ES cells were not detected, although control ES cells carrying an IL-2R gamma gene with embedded loxP sites gave rise to T-, B-, and NK-cell lineages. Germline IL-2R gamma-deficient male animals, however, developed some mature splenic B and T cells, although the absolute number of lymphocytes was almost 10-fold reduced. In contrast, there was a complete disappearance of NK cells (over 350-fold reduction). Development of gut-associated intraepithelial lymphocytes was also severely diminished, and Peyer's patches were not detected. In vitro mitogenic responses of thymocytes, IL-4-directed immunoglobulin class switch of splenocytes, and NK activity were defective. Thus, IL-2R gamma facilitates mainstream B- and T-cell generation and function and also appears to be essential for NK-cell development.

Animals↗
PubMed1995

Recurrent amyloid tumor of the parotid gland.

A case of an organ-limited amyloid tumor of the left parotid gland is described with a history of recurrence. A slowly growing parotid mass was the only symptom. After 5.5 years following local excision, the patient was readmitted with a slowly growing recurrence in the superficial lobe of the previously treated gland. Lateral parotidectomy was performed with wide excision of the infiltrated tissue and preservation of the facial nerve. Primary amyloidosis of the AL type was confirmed with immunohistochemical studies revealing staining for lambda but not kappa light chains of immunoglobulins. There has been no clinical or laboratory evidence of systemic amyloidosis or recurrence after 2 years. To the best of our knowledge, this is the first report of a recurrent amyloid tumor of the parotid gland.

Amyloid↗
PubMed1995

Does the serum level of IgA-alpha-1-antitrypsin complex correlate with radiological progression in early rheumatoid arthritis? A 3-year follow-up study.

We followed the levels of serum IgA-alpha-1-antitrypsin (IgA-AT) complex in 37 patients with early rheumatoid arthritis (RA) during the first 3 years of the disease. The changes in IgA-AT were correlated with a radiological damage score (DS) of the hands assessed according to Larsen. At the onset of the disease, the IgA-AT serum concentration was significantly higher as compared to the control group (0.72 +/- 0.22 U vs 0.29 +/- 0.14 U, P < 0.01). The level significantly decreased during the 3-year observation period. The DS was significantly higher after 3 years. However, this difference was due to changes in only 11 patients; in 26 patients the DS was almost unchanged. In the group of 11 patients with radiological progression, the level of IgA-AT either remained high or increased significantly (0.95 +/- 0.18 U at the onset, 0.97 +/- 0.25 U after 3 years), whereas we observed a decrease in IgA-AT in 26 patients without radiological progression (0.63 +/- 0.16 U at the onset of the disease, 0.45 +/- 0.10 U after 3 years, P < 0.01). Moreover, a relationship between changes in IgA-AT serum level and radiological progression was shown (r = 0.60, P < 0.01). Our studies suggested that the relationship between IgA-AT level and radiological progression of the disease should be considered. We cannot exclude the possibility that the constant high level of IgA-AT may cause worsening in bone erosions.

Adolescent↗
PubMed1995

Optical multisite monitoring of cell excitation phenomena in isolated cardiomyocytes.

An especially designed setup which consists of an inverted fluorescence microscope, an argon ion laser and a photodiode array system permits membrane potential monitoring in isolated guinea-pig ventricular cardiomyocytes, stained with the voltage-sensitive dye di-4-ANEPPS, which responds linearly with relative fluorescence changes (delta F/F) approximately -8% per 100 mV. About a dozen measuring spots covering a single cell were simultaneously monitored with a spatial and temporal resolution of 15 microns and about 20 microseconds, respectively. In general, the rising phases of the action potentials within a single cell were highly synchronized (i.e. all upstroke velocities peaked within about 20 microseconds); however, in one cell (out of 25 examined) significant (P < 0.05) time lags exceeding the signal-dependent time resolution were also found. Experiments, simultaneously performed with our optical system and a widely used patch-clamp setup, revealed a slowed and delayed response of the clamp amplifier depending on the cell access resistance. Optical monitoring during whole-cell voltage-clamping demonstrated the influence of graduated series resistance compensation. When field stimulation was used, our results clearly demonstrated the spatially dependent polarization of the cell membrane during the stimulus, as well as a highly synchronized upstroke development. Slight differences in the maximum upstroke velocities within a single cell were also found and were basically in agreement with mathematical models.

Animals↗
PubMed1995

Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: preliminary report.

In order to evaluate the relationship between serum concentrations of interleukin-10 (IL-10), IL-6, and acute phase proteins in rheumatoid arthritis (RA) patients treated with methotrexate (MTX) or intramuscular gold (IMG) we determined IL-10, IL-6, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT) in the sera of 35 RA patients. IL-10 and IL-6 levels were evaluated using an enzyme-linked immunoassay (ELISA). AGP and ACT level were measured using rocket immunoelectrophoresis. IL-10 serum level was not increased in RA patients as compared to controls (58.7 +/- 18.1 pg/ml vs. 57.2 +/- 11.9 pg/ml). IL-6 level was significantly elevated (91.6 +/- 46.9 pg/ml vs. 45 +/- 19 pg/ml, p < 0.05). CRP was significantly increased as compared to healthy controls (35 +/- 19 mg/l vs. 3 +/- 2 mg/l, p < 0.05). Patients treated with MTX or IMG presented an increased level of IL-10 and decreased amounts of IL-6, as compared to those treated with NSAID only. However, only changes between patients treated with IMG and NSAID were found to be statistically significant. A good negative correlation between IL-10 and IL-6 serum level was found (r = -0.75, p < 0.05). A positive significant correlation between IL-6 serum level and CRP (r = 0.62, p < 0.05), AGP (r = 0.78, p < 0.05) and ACT (r = 0.45, p < 0.05) was established.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Microheterogeneity of acute phase proteins in patients with clinically active and clinically nonactive osteoarthritis.

Microheterogeneity of two acute phase glycoproteins, alpha-1-acid glycoprotein (AGP) and alpha-1-antichymotrypsin (ACT), concentrations of AGP, ACT, and C-reactive protein (CRP), and levels of three cytokines: interleukin 1 beta (IL-1-beta), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were determined in 61 serum samples and 7 synovial fluids (SFs) obtained from patients (n = 61) with osteoarthritis. Using affinity immunoelectrophoresis with concanavalin A (conA), a significant decrease in the reactivity of AGP and ACT with this lectin was found in patients with clinically active osteoarthritis when compared to those with clinically nonactive disease (p < 0.001 and p < 0.05, respectively). There was no increase in the concentration of AGP, ACT, and C-reactive protein (CRP) in the sera examined. In particular, no increase in the serum level of these proteins was found in the patients with clinically active disease. Low concentrations of IL-6 and TNF-alpha were found in most sera and SFs examined. In 6 out of 7 SFs available, IL-6 concentrations were higher than in the respective serum samples but for TNF-alpha the same could be shown in one case only. Low concentrations of IL-1-beta were found in 4 serum samples obtained from patients with clinically active osteoarthritis and in no SF specimen studied. In the entire group, serum level of TNF-alpha correlated weakly with the AGP and ACT reactivity coefficients with conA (r = 0.3634, p < 0.005 and r = 0.3324, p < 0.02, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗