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Biomedical subjects

M Mueller

Publications and source records attributed to M Mueller.

At least 55 records · Page 3Linked to original sources

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

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

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

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

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

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

Role of granulocyte/macrophage colony-stimulating factor in the regulation of murine alveolar macrophage proliferation and differentiation.

Granulocyte/macrophage (GM)-CSF is one of the hemopoietic growth factors that stimulates neutrophilic granulocyte and macrophage production by bone marrow progenitor cells. In this study, the effect of GM-CSF on the growth and differentiation of murine pulmonary alveolar macrophages (PAM) was investigated. In the presence of GM-CSF, normal murine PAM were induced to proliferate and develop into macrophage colonies with a dose-response curve similar to that of bone marrow GM colony-forming cells. PAM also responded to CSF-1, a lineage-restricted growth factor, but required much higher doses of CSF-1 and a longer incubation time for optimal colony formation. The proliferative response of PAM to CSF-1, however, was greatly enhanced by the concurrent addition of low doses of GM-CSF. In contrast, low doses of CSF-1 failed to potentiate the proliferative response of PAM to GM-CSF. Macrophages derived from GM-CSF cultures were rounder and less stretched and possessed less FcR-mediated phagocytic activity than cells produced in CSF-1 cultures. A study with hydrocortisone-induced monocytopenia showed that nearly one half of lung macrophages may be sustained by local proliferation of PAM without the continuous migration of blood monocytes. This study suggests that GM-CSF may play a major role in the production of PAM by two modes of action, 1) direct stimulation of cell proliferation and 2) enhancement of their responsiveness to CSF-1, thereby producing more mature and functionally competent macrophages.

Animals

Effects of fluid resuscitation on cardiac dysfunction following thermal injury.

To test the hypothesis that low cardiac output in burns is secondary to hypovolemia, the effects of resuscitation on isovolumic contracting rat heart following a full-thickness burn were studied. Sprague-Dawley rats were randomly assigned into three groups: (1) Sham burn, (2) 30% body surface area burn nonresuscitated, (3) 30% body surface area burn with 15 cc Ringer's lactate/180 g body wt ip at the time of burn resuscitated. Twenty hours postburn, the hearts were mounted on a Lagendorff perfusion apparatus. A balloon-tipped catheter placed in the left ventricle measured pressure and dp/dt. Coronary flow was determined. Myocardial samples for ATP and water were obtained. Left ventricular function was evaluated by recording peak systolic pressure, end diastolic pressure, and maximum +/- dp/dt while balloon volume was increased to 0.3 cc. Results are with end diastolic volume constant at 0.15 cc. Compared to sham burn, burn nonresuscitated generated lower peak systolic pressure +/- dp/dt and higher end diastolic pressure while hearts from burn resuscitated generated the same as sham burn. Coronary flow and tissue water content was similar in all. ATP content was lower in burn nonresuscitated. Our data support that impaired systolic and diastolic function in burn nonresuscitated hearts is associated with lower ATP levels not seen in burn resuscitated and reperfusion of burn nonresuscitated hearts does not reverse the myocardial depressant effect.

Adenosine Triphosphate

Interleukin-3 (IL-3) stimulates the clonal growth of pulmonary alveolar macrophage of the mouse: role of IL-3 in the regulation of macrophage production outside the bone marrow.

Interleukin-3 (IL-3) is one of the hematopoietic growth factors that regulates the growth and differentiation of pluripotent stem cells, thereby leading to the production of all the major blood cell types. The role of IL-3 in the regulation of pulmonary alveolar macrophage (PAM) production was investigated. IL-3 stimulated the proliferation and clonal growth of murine PAM with a dose-response curve similar to that of bone marrow granulocyte-macrophage colony-forming cells. The IL-3-induced colony formation by cells outside the bone marrow appeared to be unique to PAM; IL-3 failed to cause colony formation by both peritoneal exudate macrophages (PEM) and blood monocytes. Unlike bone marrow stem cells, PAM are unipotential and in vitro gave rise to only mononuclear phagocytes under the influence of IL-3. Nevertheless, cells derived from PAM cultures in media containing IL-3 displayed a high degree of heterogeneity in terms of their Fc receptor-mediated phagocytic activity. At low concentrations, IL-3 induced a synergistic response with colony-stimulating factor 1 (CSF-1), which resulted in an enhanced proliferative capacity of PAM. A synergistic effect was also observed by short-term exposure of PAM to IL-3 followed by incubating with CSF-1 alone. This study shows that IL-3 exhibited a macrophage growth factor activity unique to PAM.

Animals

Parathyroid ultrastructure after aldehyde fixation, high-pressure freezing, or microwave irradiation.

Parathyroid cell variants, commonly observed in parathyroid glands fixed by immersion in glutaraldehyde, are believed to be the result of cyclic changes in the course of parathyroid hormone secretion. Immersion of bovine parathyroid glands in a mixture consisting of 1% glutaraldehyde, 1.5% formaldehyde, and 2.5% acrolein, followed by post-fixation in 1% osmium tetroxide, resulted in high uniformity with only one cell variant, whereas the same fixation procedure led to disruption of cell membranes and formation of cell variants in rat parathyroids. Parathyroid glands of both cattle and rats prepared by high-pressure quick-freezing and subsequent freeze-substitution contained only one cell variant. Excellent preservation of the ultrastructure of bovine and rat parathyroids, also exhibiting only one cell variant, was achieved by microwave irradiation in the presence of 2.5% glutaraldehyde in Na-cacodylate followed by post-fixation with OsO4 in Na-cacodylate or s-collidine, both containing Ca2+ and Mg2+. Use of the appropriate buffer, as well as osmication, is essential for successful fixation utilizing microwave energy. The main effects are considered to be heating specimens within sufficient short periods and enhancement of subsequent osmium fixation. The results support the idea, arising after examination of perfusion-fixed parathyroid tissue, that parathyroid cell variants occur during improper aldehyde fixation rather than that they express functional diversity.

Air Pressure

Damage of erythrocytes by activated oxygen generated in hypoxic rat liver.

The implication of activated oxygen in the interaction between hypoxic rat liver and circulating erythrocytes was investigated. Reduced species of oxygen generated in hypoxic liver owing to accelerated purine nucleotide degradation via xanthine oxidase initiate alterations of plasma membrane and glutathione system of erythrocytes. Osmotic fragility, hemolysis rate and erythrocytic GSSG:GSH ratio may be considered as appropriate indicators of oxidative load in liver and other tissues. Addition of erythrocytes to the perfusion medium attenuates the GSSG efflux of hypoxic liver from 2.7 +/- 0.5 nmol x g w.w.-1 x min-1 to 1.4 +/- 0.2 nmol x g w.w.-1 x min-1 Thus, circulating erythrocytes protect the liver against oxidative attack.

Animals

Influence of repeated washings with soap and synthetic detergents on pH and resident flora of the skin of forehead and forearm. Results of a cross-over trial in health probationers.

Ten healthy individuals washed their forehead and forearm twice a day over consecutive periods of four weeks with soap and synthetic detergents or vice versa (cross-over design). In general the pH values were higher during the period when soap was applied (the mean pH differed by 0.3 units, p less than 0.01). As a rule the counts of coagulase-negative staphylococci were not much altered. The number of propionibacteria, however, was markedly higher when soap was used (p = 0.02 and 0.01 resp.). At the forehead there was a clear correlation between bacterial counts and skin pH both with propionibacteria (0.56, p less than 0.001) and staphylococci (0.51, p less than 0.001). At the forearm only the former proved true (0.24, p less than 0.05). Thus the skin pH seems to be open to long-standing changes according to the preferred washing habits which may also be of major influence on the composition of the cutaneous bacterial flora.

Adult

The role of cytochrome a in the proton pump of cytochrome-c oxidase.

Cytochrome-c oxidase of bovine heart mitochondria was depleted of copper A by dialysis against 1 M KCN in the presence of dodecylmaltoside. There was no difference of the pH-dependence of the midpoint potential between the intact and the copper-depleted enzyme. Oxidation of reduced cytochrome a2+a3(3+).CN complex released about 1 proton/electron in the medium at pH 7.6. This release was inhibited by N,N'-dicyclohexylcarbodiimide. Again there was no difference between the intact and Cu-depleted enzyme. This limits the role of copper A in the mechanism of the proton pump. On the other hand, these experiments showed that cytochrome a could be a component of the proton pump.

Animals

In-home versus clinic-based services for the developmentally disabled child: who is the primary client--parent or child?

This paper analyzes two different approaches to service delivery, in-home and clinic-based, in order to assist planners and clinicians in utilizing the merits of both systems most effectively. The two systems are compared and contrasted along the following variables: team process, identified client, pace of treatment, and degree of coverage. Using these variables as a guideline, this paper proposes that the degree to which the family's priorities are similar or dissimilar to the priorities of the organization determines the degree of effectiveness of home-based or clinic-based services. This proposal is discussed and case histories illustrating this premise are presented.

Ambulatory Care Facilities