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Biomedical subjects

M Mueller

Publications and source records attributed to M Mueller.

At least 91 records · Page 5Linked to original sources
PubMed1993

Mass spectrometric identification and quantitation of arachidonate-containing phospholipids in pancreatic islets: prominence of plasmenylethanolamine molecular species.

D-Glucose induces insulin secretion from beta-cells of pancreatic islets by processes involving glycolytic metabolism and generation of ATP. Glucose also induces hydrolysis of beta-cell membrane phospholipids and accumulation of nonesterified arachidonate, which facilitates Ca2+ entry and the rise in beta-cell Ca2+ concentration that is a critical signal in the induction of insulin secretion. Glucose-induced hydrolysis of arachidonate from beta-cell phospholipids is mediated in part by an ATP-stimulated, Ca(2+)-independent (ASCI)-phospholipase A2 (PLA2), which, in vitro, prefers plasmalogen over diacylphospholipid substrates, but it is not known whether islets contain plasmalogens. We have identified and quantitated the major species of arachidonate-containing phospholipids in pancreatic islets by high-performance liquid chromatographic and mass spectrometric analyses. Arachidonate has been found to constitute 30% of the total islet glycerolipid fatty acyl mass. Ethanolamine phospholipids contain 30% of total islet arachidonate, and 44% of that amount resides in three plasmenylethanolamine molecular species with residues of palmitic, oleic, or stearic aldehydes in the sn-1 position. These endogenous islet plasmenylethanolamine species are hydrolyzed more rapidly than phosphatidylethanolamine species by islet ASCI-PLA2 in vitro and are also hydrolyzed in intact islets stimulated with secretagogues. ASCI-PLA2-catalyzed hydrolysis of islet plasmenylethanolamine species in vitro is inhibited by a selective haloenol lactone suicide substrate (HELSS) which is sterically similar to plasmalogens, and HELSS also inhibits all temporal phases of both eicosanoid release and insulin secretion from secretagogue-stimulated pancreatic islets. Islet beta-cell ASCI-PLA2-catalyzed hydrolysis of arachidonate from endogenous plasmenylethanolamine substrates may be an intermediary biochemical event in the induction of insulin secretion.

Animals↗
PubMed1993

Portal magnetic resonance angiography.

MR angiography has shown definite clinical use in the portal venous system. Methods have been developed for noninvasive assessment of portal venous anatomy and blood flow using a variety of techniques. Time-of-flight techniques for portal angiography and both time-of-flight and phase-contrast techniques for flow measurement are reviewed.

Humans↗
PubMed1993

Influence of aluminum oxalate solutions acidity and conditioning times on resin bond strength to enamel.

The present investigation demonstrated that variations in pH between 0.8 and 2.1 and in the duration of etching with an aluminum oxalate/glycine conditioning solution between 5 and 120 seconds has no influence on the retentive strength of restorative polymer to enamel, although the micromorphological appearance of enamel is clearly affected. The lower the pH of and the longer the etching time with the conditioning solution, the more pronounced is the roughness pattern generated. SEM inspection of the fracture sites following debonding of shear bond strength specimens verified consistently cohesive failure in resin close to the interface.

Acid Etching, Dental↗
PubMed1993

Endoscopic laser therapy in a case of gastric antral vascular ectasia (watermelon stomach).

We report the case history of a 75-year-old female patient suffering from extensive gastric antral vascular ectasia (watermelon stomach) with portal hypertension in alcoholic liver cirrhosis. Iron deficiency anaemia, due to chronic blood loss from the antral lesions, required repeated transfusions. Conservative treatment failed, but a surgical intervention (antrectomy) was discarded in view of concomitant diseases. Endoscopic laser photocoagulation therapy with a Nd:YAG-laser eradicated the characteristic antral lesions, which was accompanied by a significant reduction of transfusion requirements. No relapse has been observed since then. Endoscopic laser photocoagulation appears to be an efficacious and safe alternative in the treatment of gastric antral vascular ectasia.

Aged↗
PubMed1992

Selective inhibition of tumor cell growth by a recombinant single-chain antibody-toxin specific for the erbB-2 receptor.

A high percentage of human breast and ovarian tumors display amplified c-erbB-2 gene copies, leading to overexpression of the growth factor receptor. Its membrane location and elevated expression make the erbB-2 protein an appropriate target for a directed tumor therapy. We have used recombinant DNA technology to produce a single-chain antibody-exotoxin A (scFv-ETA) fusion protein which specifically binds the human erbB-2 receptor. The scFv portion is composed of the heavy- and light-chain variable domains of a monoclonal antibody which recognizes the extracellular domain of the human erbB-2 receptor. The bacterially produced scFv-ETA protein was shown to bind specifically to cells expressing the human erbB-2 protein. The scFv-ETA inhibits protein synthesis in erbB-2-expressing tumor cells at doses ranging from 2 to 200 ng/ml and is cytotoxic for these cells at equivalent doses. In athymic nude mice, administration of the scFv-ETA inhibited the growth of erbB-2-overexpressing human ovarian carcinoma cells.

ADP Ribose Transferases↗
PubMed1992

Arachidonic acid metabolism in isolated pancreatic islets. VI. Carbohydrate insulin secretagogues must be metabolized to induce eicosanoid release.

Pancreatic islets stimulated with D-glucose are known to liberate arachidonic acid from membrane phospholipids and release prostaglandin E2 (PGE2). A component of the eicosanoid release induced by D-glucose has been demonstrated to occur without calcium influx and must be triggered by other coupling mechanisms. In this study, we have attempted to identify mechanisms other than calcium influx which might couple D-glucose stimulation to hydrolysis of arachidonate from membrane phospholipids in islet cells. We have found that occupancy of the beta cell plasma membrane D-glucose transporter is insufficient and that D-glucose metabolism is required to induce islet PGE2 release because 3-O-methylglucose fails to induce and mannoheptulose prevents PGE2 release otherwise induced by 17 mM D-glucose. The carbohydrate insulin secretagogues mannose and D-glyceraldehyde have also been found to induce islet PGE2 release, but the non-secretagogue carbohydrates L-glucose and lactate do not. Carbohydrate secretagogues are known to be metabolized to yield ATP and induce depolarization of the beta cell plasma membrane. We have found that depolarization by 40 mM KCl induces PGE2 release only in the presence and not in the absence of extracellular calcium, but exogenous ATP induces islet PGE2 release with or without extracellular calcium. Carbachol is demonstrated here to interact synergistically with increasing concentrations of glucose to amplify PGE2 release and insulin secretion. Pertussis toxin treatment is shown here not to prevent PGE2 release induced by glucose or carbachol but to increase the basal rate of PGE2 release and the islet cyclic AMP content. Theophylline (10 mM) exerts similar effects. Eicosanoid release in pancreatic islets can thus be activated by multiple pathways including muscarinic receptor occupancy, calcium influx, increasing cAMP content, and a metabolic signal derived from nutrient secretagogues, such as ATP.

3-O-Methylglucose↗
PubMed1992

Does immobilization influence the systemic acceleratory phenomenon that accompanies local bone repair?

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as the regional acceleratory phenomenon (RAP). We previously showed that restoration of a local bone defect in the rat leads not only to RAP but also leads to a systemic acceleration of osteogenesis (systemic acceleratory phenomenon, SAP) in distant sites of the skeleton. In this study we investigated the impact of immobilization of the defect-bearing extremity on the development of SAP. A hole 1.2 mm in diameter was drilled in the diaphysis of the left tibia of female rats. In the experimental group (n = 15), a knee tenotomy was performed in the defect-bearing left hind leg. We examined both femora, both tibiae, and the fourth lumbar vertebra by computed x-ray densitometry on day 7 postoperatively. Immobilization of the defect-bearing limb led to a decrease in x-ray density not only of the immobilized (p < 0.0001) but also of the contralateral tibia (p < 0.0001). Both femora (p < 0.001) and the fourth lumbar vertebra (p < 0.025) of the experimental group also showed a significant decrease in x-ray density. We previously showed that SAP leads to an increase in x-ray density of both femora. This increase is no longer detectable in animals after immobilization of the defect-bearing limb. Thus we conclude that immobilization interferes with SAP. This suggests the possible dependence of SAP on mechanical load. Furthermore, these data suggest a possible impact of local immobilization on the rest of the skeleton.

Absorptiometry, Photon↗
PubMed1992

Mineral apposition rate in rat cortical bone: physiologic differences in different sites of the same tibia.

The mineral apposition rate (MAR) is a commonly used parameter for the characterization of bone formation and is often determined to test for experimental effects on cortical bone. We investigated whether there are physiologic variations in rat cortical MAR dependent on the side or site of measurement. In our experiment we used female rats. The animals were sacrificed on day 8, after double-fluorochrome labeling with calcein and tetracycline was performed. The MAR was calculated at 3.6, 5.4, 7.2, 9, and 10.8 mm from the epiphyseal growth plate of the lateral as well as of the medial endosteum of both right and left tibiae. We found a physiologic significant difference in the MAR between the lateral and the medial endosteal sites of the same tibia (p < 0.0001), especially near the epiphyseal growth plate. Regarding the same cortical side, there is a significant decrease (p < 0.0001) in the endosteal MAR with increasing distance from the epiphyseal growth plate. We conclude that the observed differences in endocortical MAR must be due to specific mechanical challenges. Because these differences are statistically significant, it is necessary to standardize the area of histomorphometric measurement not only with respect to the distance from the epiphyseal growth plate, but also with respect to the cortical side.

Analysis of Variance↗
PubMed1992

Percutaneous laser discectomy.

Percutaneous discectomy, for treatment of lumbar disc herniation, was first described in 1975 by Hijikta. Since its inception, a variety of instruments including rongeurs, augers, automated mechanical devices, and more recently, lasers have been developed to remove tissue from the herniated disc. The advantages of lasers include miniaturized, safe, and efficient energy delivery for percutaneous tissue removal. This article reviews the development of lasers for percutaneous discectomy.

Forecasting↗
PubMed1992

Treatment of stress response during balanced anesthesia. Comparative effects of isoflurane, alfentanil, and trimethaphan.

Acute hypertensive responses during nitrous oxide-opioid-relaxant anesthesia are a common clinical problem. In adult men undergoing radical prostatectomy procedures and anesthetized with a standardized technique, we evaluated the effectiveness of alfentanil, isoflurane, and trimethaphan in treating acute hemodynamic and stress hormone responses to surgical stimulation. Stress hormone concentrations were measured 1 min before skin incision, after the onset of an acute hypertensive response, and after returning the mean arterial pressure to within 10% of the preincision values with one of the three treatment modalities. Pretreatment plasma alfentanil concentrations (151 +/- 47 to 156 +/- 47 ng.ml-1) and end-tidal nitrous oxide concentrations (66 +/- 2 to 68 +/- 2%) were similar in all three groups. Acute hypertensive events were associated with significantly increased concentrations of catecholamines and vasopressin (antidiuretic hormone [ADH]). Whereas intravenous alfentanil returned all hormone concentrations to preincision values, norepinephrine and glucose concentrations were significantly increased after adjunctive isoflurane administration. Although trimethaphan decreased the norepinephrine concentration, the epinephrine, beta-endorphin, cortisol, ADH, and glucose concentrations were significantly increased compared to preincision values. However, the persistent elevation in the posttreatment ADH concentration in the trimethaphan group was the only significant difference between the three groups. Mean (+/- standard deviation) times to awakening (2.8 +/- 3.3 to 3.8 +/- 4.2 min), extubation (8.1 +/- 4.8 to 10.3 +/- 8.5 min), and orientation (19.6 +/- 20.4 to 24.6 +/- 19.1 min) were similar in all three groups. Naloxone was required more frequently in patients in the alfentanil (35%) and isoflurane (24%) groups than in the trimethaphan group (4%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Tumor necrosis factor and cardiac function.

The direct effect of tumor necrosis factor (TNF), a product of activated macrophages, on myocardial performance was determined using an isolated papillary muscle technique and a modified Langendorff preparation. Papillary muscle was obtained from male adult rats 4-5 hours after they received either 100 ng/kg TNF (group A), or 100 micrograms/kg TNF (group B) or saline (control). Group B animals exhibited significantly greater peak tension development and velocity of contraction compared with controls (p less than 0.05). In group A animals these variables were not significantly different from those of the controls (p greater than 0.05). Electrophysiologic measurements revealed a significant decrease in resting membrane potential in both group A and group B animals compared with the controls (p less than 0.05). Whole hearts perfused with serum from animals treated with TNF 18-22 hours earlier exhibited significant impairment of contractility, decreased rate of systolic pressure development, and decreased rate of relaxation compared with the controls (p less than 0.05). Coronary flow and myocardial water content were similar for both groups of perfused hearts. These data suggest that tumor necrosis factor stimulates an early beneficial effect on myocardial function, which 18-22 hours later is associated with impairment of myocardial performance. This effect appears to be serum transferable.

Action Potentials↗
PubMed1992

Validity of the Threat Index.

The validity of the Threat Index was examined in a study of 42 students and 15 HIV+ clients. When completing the Threat Index, subjects rate the self and death on 30 bipolar adjectives. A count is made of the number of times the same adjective poles are used to describe the self and death. Uses of the same poles are called matches, while uses of different poles are called splits. The Threat Index is based on the assumption that splits indicate threat. Analysis showed that neither splits nor matches were usually threatening and that neither was necessary or sufficient for the experience of threat. These results did not support the validity of the Threat Index.

Adult↗
PubMed1991

A systemic acceleratory phenomenon (SAP) accompanies the regional acceleratory phenomenon (RAP) during healing of a bone defect in the rat.

The rate of remodeling in the region of a bone defect exceeds normal tissue activity. It was Frost who described this reaction as a regional acceleratory phenomenon (RAP). We investigated the local healing process with rats with a burr hole defect (1.2 mm in diameter) in the left tibia. We differentiated an initial phase of bone formation followed by a phase of predominant resorption. To determine whether this regional enhancement of bone formation would result in a systemic impact on bone metabolism, we analyzed both tibiae and femora and the fourth lumbar vertebra. On day 7 both femora of rats with the tibial defect showed a significant increase in computerized x-ray density, dry weight, ash weight, and Ca2+ content. Both tibiae and the fourth lumbar vertebra showed a significant increase in mineralizing surface, mineral apposition rate, and bone formation rate. Because of these results we conclude that a systemic acceleratory phenomenon (SAP) accompanies the RAP. SAP affects only the cancellous, but not the cortical bone compartment. SAP is associated closely with the occurrence of woven bone during the formation phase of the healing process. Thus we assume that woven bone formation plays a pivotal role in the mediation of SAP.

Absorptiometry, Photon↗
PubMed1991

Chronic inflammation is associated with an increased proportion of goblet cells recovered by bronchial lavage.

To evaluate the possibility that bronchoalveolar lavage could provide sufficient respiratory epithelial cells to quantify changes in epithelial cell types associated with chronic inflammation, we examined the epithelial cells obtained in the first infused (20 ml) aliquots that were processed separately from later aliquots, a process known to enrich for bronchial contents. Epithelial cells, including ciliated cells, goblet cells, and fragments of desquamated epithelium, were easily identified after preparation by cytocentrifugation and staining with a modified Giemsa stain. Quantification of the columnar cell types revealed that those with chronic bronchitis and asymptomatic smokers have increased goblet cells as a percentage of the total columnar epithelial cells (chronic bronchitics 36 +/- 2 percent, asymptomatic smokers 22 +/- 2 percent) compared with normal subjects (9 +/- 1 percent, p less than 0.001, ANOVA). Significantly, the goblet cell percentage was strongly correlated with other measures of bronchitis and measures of airflow obstruction such as the bronchitis index, a visually derived score at bronchoscopy of airway inflammation (r = 0.72, p less than 0.001), the percent neutrophils in the first infused aliquots (r = 0.44, p less than 0.05), and the FEV1 percent (r = -0.74, p less than 0.001). Thus, bronchoalveolar lavage is capable of providing sufficient bronchial epithelial cells for analysis, and the changes seen in the spectrum of columnar epithelial cells may reflect important underlying pathologic changes.

Airway Obstruction↗
PubMed1990

Recombinant tumor necrosis factor enhances the proliferative responsiveness of murine peripheral macrophages to macrophage colony-stimulating factor but inhibits their proliferative responsiveness to granulocyte-macrophage colony-stimulating factor.

Tumor necrosis factor (TNF) is a protein produced by activated macrophages in response to endotoxin. The effect of recombinant murine TNF (rMuTNF) on the growth of murine tissue-derived macrophage colony-forming units (CFU-M) which are responsive to both macrophage and granulocyte-macrophage colony-stimulating factors (M-CSF and GM-CSF), was studied. TNF alone did not stimulate macrophage proliferation but did prolong their survival in vitro. The proliferative response of CFU-M to M-CSF, however, was greatly enhanced by the presence of TNF. The enhancement effect of TNF is dose-dependent, reaching a maximum at approximately 50 U/mL. In contrast, the proliferative responsiveness of CFU-M to GM-CSF was inhibited by the concurrent addition of rMuTNF. Both effects appear to be caused directly by rMuTNF, rather than by the secondary factor(s) produced by TNF-treated macrophages. TNF treatment also induced a transient downmodulation of M-CSF receptors in cultured macrophages and accelerated their uptake and use of exogenous M-CSF, which may account for, at least in part, the enhanced proliferative activity in response to M-CSF. Short-term treatment (24 hours) was not sufficient to induce either an enhancing or an inhibitory effect upon CFU-M. This study suggests an autoregulatory role for TNF in the production of mature tissue macrophages by selectively enhancing their proliferative response to lineage specific growth factor, M-CSF.

Animals↗
PubMed1990

Inhibition of TPA-induced monocytic differentiation in THP-1 human monocytic leukemic cells by staurosporine, a potent protein kinase C inhibitor.

THP-1 is a factor-indepencent, monocytic leukemia cell line which differentiates into adherent macrophages upon treatment with 12-O-tetra-decanoylphorbol-13-acetate (TPA). Unlike its normal counterparts, THP-1 cells display only minimal levels of proto-oncogene c-FMS RNA which encode for membrane M-CSF receptors. Northern blot analysis showed that the c-FMS mRNA levels in THP-1 cells was greatly enhanced during TPA-induced monocytic differentiation. Despite the acquisition of functional activities and induction of c-FMS transcripts after TPA treatment, no surface M-CSF receptors were detected on the THP-1 cells. The inducing activity associated with TPA was completely abrogated when THP-1 cells were pretreated with staurosporine, a potent protein kinase C (PK-C) inhibitor. It is concluded that the activation of the PK-C system is a part of the metabolic cascade essential for the initiation of monocytic differentiation in THP-1 cells.

Alkaloids↗
PubMed1989

Translation in Saccharomyces cerevisiae: initiation factor 4A-dependent cell-free system.

Yeast Saccharomyces cerevisiae genes TIF1 and TIF2 (translation initiation factor) encode a protein tentatively called translation initiation factor (Tif) due to the similarity of its amino acid sequence and its molecular weight to mammalian eukaryotic initiation factor 4A. To clarify whether Tif is involved in translation, we produced an affinity-purified anti-Tif antibody by using Tif isolated from a Tif-overproducing yeast strain as immunogen and an Escherichia coli strain expressing Tif from an expression vector to provide the extract for affinity purification of the antibody. By using chromatographic procedures and the affinity-purified anti-Tif antibody as probe to identify Tif-containing fractions, we purified Tif from wild-type yeast cells. When yeast cells containing the only TIF1 gene on a plasmid under the control of the galactose-inducible CYC1-GAL10 promoter were grown in medium containing glucose as the carbon source, the production of Tif was shut off and growth was arrested. Lysates made from these cells were inactive in in vitro translation. Addition of Tif to these lysates restored in vitro protein synthesis. These results show that Tif is a translation factor, the yeast homologue of mammalian translation initiation factor 4A.

Blotting, Western↗