Search PubMed⌕ Search

Biomedical subjects

R N Moore

Publications and source records attributed to R N Moore.

At least 91 records · Page 5Linked to original sources

Fine structural and biochemical effects of aminoglutethimide and o,p'-DDD on rat adrenocortical carcinoma 494 and adrenals.

Rats bearing adrenocortical carcinoma 494 were injected daily for 7, 14, or 21 days with aminoglutethimide (AG) or o,p'-DDD. Reversibility of these steroidogenic inhibitors was determined by injecting other animals for either 14 or 21 days and sacrificing them 14 days later. While the drugs had little effect on body or tumor growth, plasma corticosterone levels were reduced a maximum of 88% in normal and 95% in tumor-bearing rats during AG chemotherapy. These levels were unaltered in normal rats by o,p'-DDD and reduced a maximum of 64% in tumor-bearing animals. Relative adrenal weights generally increased during chemotherapy and then returned to control levels. These changes were mainly due to alterations in the lipid and mitochondrial volume fractions. Lipid increased with both drugs while mitochondria increased with o,p'-DDD and decreased with AG. Cholesterol ester levels paralleled the lipid stereology more closely with AG than o,p'-DDD. With both drugs the most notable changes in tumor fine structure was a decrease in mitochondrial internal membranous vesicles and matrical density. Adrenal mitochondria had the irregular, elongated forms characteristic of tumor-bearing animals and were vacuolated (AG) or had internal rings (o,p'-DDD). The large lipid droplets observed during chemotherapy with both drugs were replaced by numerous small droplets in recovery periods.

Adrenal Cortex↗

The primary role of lymphoreticular cells in the mediation of host responses to bacterial endotoxim.

Mice that are unresponsive to lipopolysaccharide (LPS) (strain C3H/HeJ) can be rendered LPS-sensitive by the adoptive transfer of bone marrow cells from LPS-sensitive mice (strain C3H/HeN). This model of adoptive transfer was used to evaluate the contribution of lymphoreticular cells to five effects of endotoxin on the host: immunogenicity, adjuvanticity, lethality, induction of interferon, and induction of colony-stimulated factor. C3H//HeJ mice became sensitive to each of these effects after adoptive transfer of bone marrow cells from C3H/HeN mice. The efficacy of transfer was directly proportional to the dose of X-irradiation and inversely proportional to the number of surviving host stem cells. The most effective dose of radiation was 850 rad, and C3H/HeN leads to C3H/HeJx chimeras prepared at this dose were as sensitive to LPS for each parameter tested as were the C3H/HeN donors except for a threefold greater resistance to lethality than LPS-responsive C3H/HeN mice. C3H/HeN mice could also be rendered unresponsive to LPS by the adoptive transfer of C3H/HeJ bone marrow cells. C3H/HeN chimeras were resistant to all of the effects of LPS studied except for the induction of colony-stimulating factor. These results demonstrate that lymphocytes and/or macrophages play a primary role in mediating a number of diverse and seemingly unrelated host responses to endotoxin.

Adjuvants, Immunologic↗

Macrophages as a source of tumoricidal activity (tumor-necrotizing factor).

Macrophage-enriched peritoneal exudate cells from mice infected with Mycobacterium bovis BCG, macrophage-like tumor cells (PU 5-1.8), and peritoneal macrophages propagated in vitro with macrophage growth factor released tumoricidal activity into the culture medium within 2 to 3 h after stimulation with nanogram quantities of bacterial lipopolysaccharide. The cytotoxic activities from each of the macrophage culture supernatants eluted from diethylaminoethyl-Sephacel columns at a sodium chloride concentration of 200 mM exhibited a molecular weight of 50,000 to 60,000 as estimated by gel filtration, were stable at 56 degrees C for 30 min, and were active at a pH range of 6 to 10. A rabbit antiserum directed against serum-derived cytotoxic activity (tumor-necrotizing factor) from BCG-infected and lipopolysaccharide-challenged mice inhibited all of the cytotoxic activities generated in vitro. This suggests that the macrophage-derived cytotoxins are identical with serum-derived cytotoxic factor, which further implies that the macrophage is the cellular source of tumor-necrotizing factor.

Animals↗

Role of lipopolysaccharide in regulating colony-stimulating factor-dependent macrophage proliferation in vitro.

Bacterial lipopolysaccharides (LPS) enhance both production of colony-stimulating factors (CSF) and proliferation of mononuclear phagocytes in vivo. The present study was undertaken to determine whether the effects of LPS on CSF-dependent monopoiesis are due solely to enhanced production of CSF or also to direct effects of LPS on the responding progenitor cell. Addition of LPS to CSF-stimulated macrophage populations had different effects, depending upon the concentration of CSF in the cultures. In the presence of optimal to supraoptimal concentrations of CSF, LPS at doses >/=0.01 mug/ml inhibited macrophage colony formation. This inhibitory activity was not due to cytotoxicity of the LPS and was not mediated through prostaglandin synthesis. In the presence of suboptimal concentrations of CSF, minute concentrations of LPS (10(-7) mug/ml) significantly enhanced macrophage colony formation. Both effects of LPS (inhibition and enhancement) appeared to be properties of lipid A since neither effect was noted with cells from LPS-resistant C3H/HeJ mice, whereas both effects could be neutralized by the addition of the antibiotic polymyxin B, which binds to the lipid A portion of LPS. These results suggest that the effects of LPS on monopoiesis in vivo may not be due solely to its capacity to stimulate production of CSF. Rather, LPS may be involved in stimulating monopoiesis both indirectly through stimulation of CSF production and by its effects on the CSF-responsive progenitor cell.

Animals↗

BCG-induced enhancement of endotoxin sensitivity in C3H/HeJ mice. I. In vivo studies.

C3H/HeJ mice exhibit a marked insensitivity to bacterial lipopolysaccharide (LPS) in vivo. Pretreatment of these mice with viable BCG organisms 11 days before LPS administration renders them sensitive to the lethal effects of a highly purified, phenol-extracted LPS. Other in vivo responses to LPS are increased in BCG-infected C3H/HeJ mice in parallel with enhanced lethality. These include 1) the elevation of serum interferon, 2) the production of the acute phase reactant, serum amyloid A (SAA), and 3) hypoglycemia. However, BCG infection has only a minimal effect on anti-LPS antibody production. BCG-infected C3H/HeJ mice approach the LPS sensitivity of normal C3H/HeN mice, but the enhanced LPS sensitivity is transient and decreases over a 2-month period. The ability of BCG to induce LPS sensitivity in C3H/HeJ mice demonstrates that LPS unresponsiveness is not due to an absolute defect in this strain, but rather, a partially reversible state of hyporesponsiveness. In addition, these findings, in conjunction with other observations, suggest that the enhancement of LPS sensitivity induced by BCG infection is mediated primarily through an effect on T cells and/or macrophages rather than B lymphocytes.

Animals↗

Production of lymphocyte-activating factor (Interleukin 1) by macrophages activated with colony-stimulating factors.

Murine peritoneal exudate macrophages incubated with medium conditioned by L929 cells were stimulated to produce lymphocyte-activating factor (LAF, Interleukin 1). This stimulatory activity was partially neutralized by antiserum prepared against partially purified L cell colony-stimulating factor (CSF) and comigrated upon gel filtration with the myeloproliferative activity. LAF-inducing activity of three different L cell CSF preparations, including one purified to homogeneity, was dependent upon the concentration of CSF. A minimum of 1,000 to 3,000 units of CSF activity was required to stimulate macrophagfes to produce LAF. Concanavalin A (Con A) stimulated splenic supernatants also contained CSF and LAF-inducing activities that co-eluted upon gel filtration. LAF-inducing activities co-eluting with the two Con A CSF peaks (apparent m.w. of 25,000 and 35,000) were effective at minimum dilutions containing 1,000 to 3,000 units of CSF activity correlating in potency with L cell-derived CSF. Based on these data, it is proposed that CSF, whether of L cell or lymphoid origin, not only has myeloproliferative activities but also is capable of stimulating macrophages to produce LAF.

Animals↗

Academic and disciplinary dismissal in dental education: the legal basis.

The courts have traditionally granted universities absolute discretion in determining whether a student has met the academic requirements of the institution and have not interfered in dismissals unless there was a clear indication that the action was arbitrary, capricious, or in bad faith. Recent court cases are cited that indicate that the courts are now beginning to require that students be informed of academic (including clinical) deficiencies and be provided the opportunity to correct the problem. When the dismissal is for disciplinary rather than academic reasons, more procedural due process is required. Although a formal judicial hearing is unnecessary, the dental administrator should be given an opportunity to hear both sides of the issue in considerable detail and the student should be given the essential elements of procedural due process of law.

Behavior↗

Prostaglandin regulation of colony-stimulating factor production by lipopolysaccharide-stimulated murine leukocytes.

The production of colony-stimulating factor by lipopolysaccharide-stimulated murine peritoneal leukocytes and their adherent subpopulations (greater than 80% macrophages) was markedly enhanced by indomethacin at concentrations sufficient to block prostaglandin E synthesis. Addition of physiological concentrations of E-series prostaglandins reversed this enhancing effect of indomethacin in a dose-dependent manner. These results indicate that colony-stimulating factor production by stimulated leukocytes is regulated by E-series prostaglandins and suggest that prostaglandins function to limit myelopoiesis by inhibiting colony-stimulating factor production and concomitantly the induction of cell proliferation.

Animals↗

Sensitization of tolerant mice to cold with a serum factor induced by endotoxin.

Endotoxin-tolerant mice are sensitized to cold (5 degrees C) stress by an injection of 0.4 ml serum collected from zymosan-pretreated mice 2 h after an intravenous (iv) injection of 25 microgram endotoxin. Deaths begin after 6 h and most animals die by 10 h, The factor in serum believed to be responsible for this effect is called glucocorticoid antagonizing factor (GAF). Tolerant mice given 10 microgram endotoxin live for 10 h and two-thirds survive for 24 h. Serum from endotoxin-poisoned conventional mice reduces survival time significantly but not as dramatically as that from zymosan-primed mice. The latter serum, but not endotoxin, causes a rapid drop in the core temperature of tolerant mice housed at 5 degrees C and inhibits the endogenous induction of phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) in tolerant mice exposed for 4--5 h to the cold. An injection of 25 microgram endotoxin does not have this effect on the enzyme. Serum that produces these responses also sensitizes mice to endotoxin lethality and blocks the protection normally afforded against endotoxin by adrenocorticoids.

Adrenal Cortex↗

Effect of Sindbis birus infection on survival of mice in the cold.

Mice infected with 10(9) plaque-forming units (PFU) of Sindbis virus 9 h prior to exposure to cold (5 degrees C) died more rapidly after entering the new environment than saline-injected control mice. The early deaths occurred in animals singly housed without bedding and only when food was withheld. Because deaths could be prevented by providing the infected animals with food, it was concluded that metabolic alteractions resulting from the virus infection were responsible for the deaths. As evidence, corticosteroid-inducible hepatic enzymes did not respond to hydrocortisone administration in virus-infected mice housed at 5 degrees C. Phosphoenolpyruvate carboxykinase (PEPCK) (EC 4.1.1.32) was induced significantly in control mice held at 5 degrees C for 5 h, but failed to induce in infected mice in the cold. Tryptophan oxygenase (TO) (EC 1.13.11.11) activity was also induced in control mice at 5 degrees C, but was too low to be measured in livers of all infected mice including those exposed to cold. The conclusion that Sindbis virus-infected mice were unable to make the metabolic adjustments required for survival at 5 degrees C was further indicated by severe hypoglycemia and rapid drop in rectal temperature that occurred in infected mice after 5 h in the cold.

Animals↗

Rat adrenocortical carcinoma 494: an integrated structural, stereological, and biochemical analysis.

Snell adrenocortical tumor 494 was implanted into male Sprague-Dawley rats and recovered 7, 14, 21, 28 or 35 days following initial detection by palpation (7-10 days following transplantation). Electron microscopic, stereological and biochemical analyses of the tumor were compared to adrenals of normal animals to serve as a baseline for further studies of the effects of chemotherapeutic agents on tumor cells. Tumor cells possessed oval or elongated mitochondrial profiles with tubular cristae, one or two very large (greater than 5 micrometer) lipid droplets, abundant ribosomes and coated vesicles, and sparse rough and smooth endoplasmic reticulum. Stereologic evaluation revealed that tumor lipid volume was 41% and mitochondrial volume 29% that of the normal adrenal controls. Tumor nuclei were 2.5 times larger than adrenocortical nuclei while cellular volumes were similar. On a net weight basis, tumor cholesterol was 55%, cholesterol ester 2.2%, and lipid phosphate 25% of respective mean values for normal adrenal glands. The tumor cholesterol: cholesterol ester ratio progressively decreased with time but remained 18-fold greater than the normal adrenal. Plasma corticosterone levels in tumor-bearing rats were elevated 3-fold by 14 days and initial detection. The adrenals of the tumor-bearing host exhibited marked involution, the extent of which was directly related to tumor size.

Adrenal Cortex Neoplasms↗

Pulsating forces in orthodontic treatment.

A controlled pulsating-force system for the orthodontic movement of teeth was designed and its biologic effects were examined, with the dog serving as an experimental model. This system was applied to the maxillary right second premolar while a continuous force was delivered to the maxillary left second premolar. After a 12-day experimental period in which pulsating forces were used, the amount of tooth movement and the radiographic and histologic changes were comparable to those produced by continuous force. These preliminary data indicate that forces of greater magnitude and duration will be necessary to more fully characterize the potential advantages of a pulsating orthodontic force.

Alveolar Process↗

Elicitation of endotoxemic effects in C3H/HeJ mice with glucocorticoid antagonizing factor and partial characterization of the factor.

C3H/HeJ mice were used to study the origin and nature of endotoxin-induced glucocorticoid antagonizing factor (GAF). In conventional mice GAF is believed to be responsible for a variety of effects that occur as a result of an injection of endotoxin, including the inhibition of hormonal induction of hepatic phosphoenolpyruvate carboxykinase and of glyconeogenesis. Responses in such animals are seen whether the endotoxin is extracted with phenol-water or with trichloroacetic acid. C3H/HeJ mice do not respond (or produce GAF?) after an intravenous injection of phenol-water lipopolysaccharide, but they react normally (produce GAF?) when given a trichloroacetic acid preparation. They also behave the same as conventional animals when injected with serum from poisoned normal mice, especially when the reticuloendothelial system of the donors has been activated by prior injections of Zymosan or heat-killed tubercle bacilli. The C3H/HeJ mice have been used, therefore, as assay animals to establish that peak levels of GAF appear in donor serum about 2 h after an injection of lipopolysaccharide, and it is produced intraperitoneally in C3H/HeJ mice given a mixture of endotoxin and peritoneal exudate cells derived from responder mice. GAF elutes from Sephadex G-200 along with markers of known molecular weight in the region of 100,000 to 200,000. It is inactivated by trypsin and by heating at 75 degrees C for 1 h.

Animals↗

The cranial base in fetal Macaca nemestrina: a quantitative analysis of size and shape.

The applicability of Fourier analysis to quantitate the midsagittal cranial base has been demonstrated utilizing fetal Macaca nemestrina. This methodology accurately measures the irregular form of the endocranial profile, minimizes the effects of size, and maximizes shape differences. This method provides a quantitative dimension to the descriptive analysis of shape change previously observed with a combined histologic and cephalometric analysis.

Animals↗