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Biomedical subjects

M Mueller

Publications and source records attributed to M Mueller.

15 recordsLinked to original sources
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

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↗
PubMed1978

Fibrinogen-fibrin transformations characterized during the course of reaction by their intermediate structures. A light scattering study in dilute solution under physiological conditions.

Intermediate structures of human fibrin formed under physiological conditions were investigated by means of light scattering in the course of the polymer/network formation. Very low fibrinogen concentrations (c = 0.03--0.13 mg/ml) were used to lower the polymerization rate, and thrombin at five concentrations (0.0085--0.04 N.I.H./ml) was used for initiation. The light scattering data were evaluated from (i) a Zimm plot, (ii) a Holtzer plot, i.e., hRtheta/Kc vs. h2, and (iii) a Kratky plot, i.e., h2Rtheta/KC vs. h2. In the beginning of the polymerization process rod-like structures are formed. The dimensions of the rod-like monomeric unit in the fibrin polymer are 112 X 3.9 nm and agree with the dimensions of fibrinogen, which also was found to be a thin rod of 105 +/- 10 nm length and 3.9 nm diameter. The mass per unit length, obtained from the asymptote in the Holtzer plot, initially increases only slightly but for high thrombin concentrations increases steeply when a critical length of 1000 nm is exceeded. At this point also the total scattering behaviour changes considerably. The upturn in the Zimm plot and the occurrence of a maximum in the Kratky plot are clear indications for the onset of branching. At low thrombin concentrations the kink in the curve of Mw/Lw against Mw becomes smoothed out because of nonspecific side-by-side aggregation of fibrin strands. The results are discussed and compared with earlier findings by others, and lead to the following conclusions. (i) Fibrinogen is a polymer with some flexibility and can exist in conformations of a stretched rod 105 nm in length, a folded rod of 45 nm in length, and a banana-like conformation of 94 nm circumference. (ii) Under the conditions of the present work, fibrinogen has the thin stretched rod conformation, and has the same dimensions as the repeating unit in the fibrin polymer. (iii) After approx. 10--12 units, end-to-end aggregated monomer branching occurs. (iv) The end-to-end aggregation is promoted by the cleavage of A peptides, branching is caused by the cleavage of B peptides while side-by-side aggregation of strands is caused by nonspecific van der Waals interaction.

Fibrin↗
PubMed1978

Growth state-dependent phenotypes of adult hepatocytes in primary monolayer culture.

A proliferation-competent adult rat liver cell monolayer system has been analyzed for tissue-specific functions during its growth cycle. High levels of the adult (L type) form of pyruvate kinase (EC 2.7.1.40) and glutathione S-transferase B ("ligand," EC 2.5.1.18) are observed during the early lag phase; they decline markedly during the logarithmic phase and reappear during the stationary phase. By contrast, elevated levels of the fetal (K type) form of pyruvate kinase and alpha1-fetoprotein production appear only after proliferation begins; this pattern diminishes slightly during stationary phase as the adult phenotype is restored. Albumin production continues throughout the entire growth cycle. These in vitro findings simulate those observed during hepatoproliferative transitions in the intact animal and, as such, constitute a developmental program for normal epithelial cells in primary culture.

Albumins↗
PubMed1978

Septic bursitis.

Explore the source record for details and available documents.

Bursitis↗
PubMed1977

Graded global ischemia and reperfusion. Cardiac function and lactate metabolism.

The effect of global ischemia of different degrees of severity and reperfusion was studied in the isolated working rat heart. Four degrees of ischemia were induced by reducing the control total coronary flow of 8 ml/min to 0, 0.04, 0.4, or 0.8 ml/min for 30 minutes, after which the coronary flow was returned to the control level. After severe ischemia (0 and 0.04 ml/min ischemic coronary flow groups), recovery of contractility was to less than 30% of the control, pre-ischemic value of ventricular developed pressure and dP/dt, and irreversible cardiac contracture and an increased pacing threshold occurred. After moderate ischemia (0.4 and 0.8 ml/min ischemic coronary flow groups), contractile function recovered completely, ischemic contracture was rapidly reversible and the pacing threshold did not increase. The moderately ischemic groups were able to function at a stable, low level of contractility for the 30 minute ischemic period, whereas the severely ischemic groups had no contractile activity. The amount of calculated tissue lactate accumulation correlated with the occurrence of irreversible ischemic injury; the severely ischemic groups which failed to recover with reperfusion accumulated 3-5 times as much lactate as the moderately ischemic groups which recovered completely. The results suggest that relatively small differences in the severity of the ischemic condition can markedly affect the degree of tissue injury.

Animals↗
PubMed1975

Methods of identification and confirmation of abusive drugs in human urine.

A thin-layer chromatography (TLC) procedure is described to be used as the initial drug detection method for urine surveillance in a drug abuse treatment program. While the TLC method is sufficiently sensitive, it is prone to false-positive results. For this reason, two other drug detection methods (gas-liquid chromatography and radioimmunoassay) have been incorporated to confirm positive results obtained with TLC. The combined methodologies result in a urine surveillance procedure that is versatile, sensitive and highly reliable.

Amphetamine↗