Biomedical subjects

D L Coleman

Publications and source records attributed to D L Coleman.

At least 91 records · Page 5Linked to original sources

PubMed1986

Gangliosides block the inhibition of macrophage Fc-dependent phagocytosis by lipopolysaccharide.

The mechanism whereby bacterial lipopolysaccharide (LPS) exerts its biologic effects on mammalian cells is unknown. Plasma membrane gangliosides bind bacterial toxins and have been implicated in modulating the effects of a variety of immunoregulatory substances. We investigated the possibility that gangliosides can inhibit the effect of lipopolysaccharide on Fc-dependent phagocytosis by murine peritoneal macrophages. Protein-free lipopolysaccharide preparations significantly inhibited Fc-mediated phagocytosis (less than 71% of control) at concentrations of 100 ng/ml or greater after 90 min of incubation. The inhibitory effect of LPS (1 micrograms/ml) was blocked when macrophages were incubated with mono-, di-, or trisialogangliosides (25-50 micrograms/ml). Neither asialoganglioside nor sialic acid alone were capable of blocking the effect of LPS. When chromatographed separately on a Sepharose 4B column, LPS and trisialoganglioside had different elution profiles. LPS and trisialoganglioside coeluted, however, when premixed at 37 degrees C for 60 min and then applied to the column. Therefore, abrogation of the effect of LPS on Fc-dependent phagocytosis may occur as a consequence of direct interaction between LPS and gangliosides. These data suggest that gangliosides may modulate the response of macrophages to bacterial lipopolysaccharide.

Animals↗

PubMed1986

Maintenance of murine oocyte meiotic arrest: uptake and metabolism of hypoxanthine and adenosine by cumulus cell-enclosed and denuded oocytes.

To analyze the potential mechanisms by which hypoxanthine and adenosine maintain meiotic arrest in mouse oocytes this study focused on: the uptake and metabolism of hypoxanthine and adenosine; the effect of inhibitors of inosine monophosphate (IMP) dehydrogenase on purine-mediated meiotic arrest; and the role of adenosine metabolism on the maintenance of meiotic arrest. Although the denuded oocyte can take up radiolabeled hypoxanthine and adenosine, an intact cumulus oophorus greatly augments uptake of these molecules (and/or metabolites). Both of these compounds were completely metabolized during incubation in vitro: hypoxanthine was apparently metabolized to uric acid and adenosine was metabolized to ADP; a small amount of each compound was also converted to inosine by cumulus cells and transferred to the oocyte. The IMP dehydrogenase inhibitors, bredinin and mycophenolic acid (MA), induced, in a dose-dependent manner, the resumption of maturation in cumulus cell-enclosed oocytes maintained in meiotic arrest by hypoxanthine but had no effect on denuded oocytes. MA did not induce maturation when meiotic arrest was maintained by guanosine. Nor did MA alter the uptake of hypoxanthine by cumulus cell-enclosed oocytes. The poorly metabolized analog of adenosine, 2-chloroadenosine, was as effective as adenosine in its synergistic action with hypoxanthine in maintaining meiotic arrest. It is concluded that hypoxanthine and adenosine are metabolized within the oocyte-cumulus cell complex; xanthyl and/or guanyl compounds are produced by oocyte-cumulus cell complexes in the presence of hypoxanthine and play an important role in the maintenance of meiotic arrest; and adenosine need not be metabolized to act synergistically with hypoxanthine in maintaining meiotic arrest.

2-Chloroadenosine↗

PubMed1986

Effects of ultra high speed floor burnishing on air quality in health care facilities.

Effects of ultra high speed (UHS) floor burnishing upon air quality in health care facilities were evaluated. A 2,000-rpm burnisher can disseminate high-velocity (190 km/hr) dust and microbial particles. A UHS burnisher used with either inadequate or no air restraint produced significant increases (P less than 0.05) in the levels of airborne dust particles and microorganisms. A UHS burnisher equipped with an air restraint assembly specifically designed for use in health care facilities produced no significant increase (P greater than 0.05) in the levels of airborne dust particles or microorganisms when compared to ambient air levels. The types and distribution of airborne microorganisms isolated from microbial air samples were not unusual nor were they directly influenced by the floor burnishing processes. Furthermore, the UHS floor burnishing process produced a significant reduction (P less than 0.05) in microbial floor contaminants (96%). When the use of UHS floor burnishing is contemplated for productivity improvement and esthetic enhancement, the possible adverse effects on air quality should also be considered.

Air Microbiology↗

PubMed1986

Keratinocyte-derived T-cell growth factor: a T-cell growth factor functionally distinct from interleukin 2.

T-cell growth factor, more recently termed interleukin 2 (IL-2), is the product of activated T lymphocytes and is considered the principal trophic factor for T lymphocytes. The activity of IL-2 preparations is assessed by the degree to which they support the growth of various IL-2-dependent cell lines. We report that murine epidermal epithelial cells (keratinocytes) produce and release a factor that supports the growth of the helper-T-cell-derived, IL-2-dependent cell line HT-2. This substance, keratinocyte-derived T-cell growth factor (KTGF), does not support the growth of an IL-2-dependent cell line derived from cytotoxic T cells (line CTLL-2). This differential effect on IL-2-dependent cell lines is unique to KTGF. KTGF has an apparent molecular weight of 25,000-35,000 and has properties similar to those of conventional IL-2 by reversed-phase and gel-filtration HPLC analysis. However, even highly purified KTGF fails to stimulate the proliferation of CTLL-2 cells. The observation that epidermal epithelium produces a trophic factor for T lymphocytes may help explain the basis for preferential proliferation of T cells in the microenvironment of skin in certain dermatologic disorders. Further, it suggests that different IL-2-dependent T-cell lines may have distinct growth requirements and that non-lymphocyte cell types may produce factors capable of maintaining the growth of T cells.

Animals↗

PubMed1986

Ion transport across cat and ferret tracheal epithelia.

Sheets of trachea from ferret and cat were mounted in Ussing chambers and continuously short circuited. Under resting conditions, in both the cat and ferret there was little or no Cl secretion, and Na absorption accounted for most of the short-circuit current (Isc). Ouabain (10(-4) M, serosal bath) reduced Isc to zero in 30-60 min. This decline was matched by a decrease in net Na absorption. Amiloride (10(-4) M, luminal bath) caused a significant decrease in Isc and conductance (G) in both species. Bumetanide (10(-4) M, serosal bath) had negligible effects on Isc and G. In both species, isoproterenol increased Isc by stimulating Cl secretion. Methacholine induced equal amounts of Na and Cl secretion, with little change in Isc. In the cat, prostaglandins E2 and F2 alpha and bradykinin increased Isc, responses which were abolished in Cl-free medium. In open-circuited cat tissues, Na flux from the serosal to mucosal side was measured simultaneously with the secretion of nondialyzable 35S. Prostaglandins E1, E2, and F2 alpha, histamine, bradykinin, methacholine and isoproterenol all increased both Na and 35S-mucin secretion.

Amiloride↗

PubMed1986

Trimethoprim-sulfamethoxazole or pentamidine for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A prospective randomized trial.

Forty patients with the acquired immunodeficiency syndrome (AIDS) and their first episodes of Pneumocystis carinii pneumonia were assigned at random to receive either trimethoprim-sulfamethoxazole or pentamidine isethionate. The two groups did not differ significantly in the severity of pulmonary or systemic processes at enrollment. Five patients treated initially with trimethoprim-sulfamethoxazole and one patient treated initially with pentamidine died during the 21-day treatment period (p = 0.09, Fisher's exact test). No significant differences were seen between groups in rates of improvement, pulmonary function tests, or 67Ga uptake by the lungs in the survivors at completion of therapy. Adverse reactions necessitated changing from the initial drug in 10 patients in the trimethoprim-sulfamethoxazole group and 11 in the pentamidine group. Minor reactions occurred in all patients. In patients with AIDS, trimethoprim-sulfamethoxazole and pentamidine do not have statistically significant differences in efficacy or frequency of adverse reactions.

Acquired Immunodeficiency Syndrome↗

PubMed1986

Antibody to the retrovirus associated with the acquired immunodeficiency syndrome (AIDS). Presence in presumably healthy San Franciscans who died unexpectedly.

We performed autopsies and serologic tests in 189 subjects (152 men and 37 women) between 20 and 50 years of age with no history of immunosuppression who died unexpectedly and whose bodies were referred to the San Francisco coroner's office. Forty-eight of the 88 single men for whom addresses were available lived in areas of the city with a high incidence of the acquired immunodeficiency syndrome (AIDS). In addition, 36 of the subjects (30 men) were intravenous drug abusers. Antibody to the retrovirus associated with AIDS was present in 23 (18%) of the 121 subjects whose sera were tested. However, neither pathologic nor laboratory manifestations of AIDS were present in any of the 189 subjects who underwent autopsy. These results suggest that antibody to the retrovirus is common but subclinical manifestations of AIDS are uncommon in San Francisco, a city where the incidence of clinical AIDS is high.

Acquired Immunodeficiency Syndrome↗

PubMed1985

Ganglioside alterations in stimulated murine macrophages.

A two-dimensional thin-layer chromatographic technique has been used to separate and display gangliosides from murine peritoneal macrophages in different functional states. Resident macrophages have a relatively simple ganglioside pattern with about 15 resorcinol-positive spots. Gangliosides from resident cells contained mostly (90%) N-glycolylneuraminic acid. Thioglycolate-elicited and Corynebacterium parvum-activated macrophages have much more complex patterns with about 40 resorcinol-positive spots. Although ganglioside sialic acid content of stimulated macrophages was only slightly higher than that of resident cells, it consisted of nearly equal amounts of N-acetyl- and N-glycolylneuraminic acid. The shift in the ganglioside sialic acid type and the expression of different gangliosides in macrophages upon stimulation may help explain some of the differences in function and responsiveness noted in these macrophage populations.

Animals↗

PubMed1985

Effect of lipopolysaccharide on the stimulation of macrophage Fc-dependent phagocytosis by splenic B lymphocytes.

Macrophage phagocytic activity is regulated by a variety of products derived from activated lymphocytes. It has been reported that nonactivated splenic B and T lymphocytes enhance macrophage glucose metabolism. In addition, the enhancement of macrophage glucose metabolism was further increased by direct effects of bacterial lipopolysaccharide (LPS) on B, but not T, lymphocytes. In the present study, the effect of purified murine splenic B and T lymphocytes on Fc-dependent phagocytosis by thioglycollate-elicited peritoneal macrophages in the presence or absence of LPS has been investigated. Fc-dependent phagocytosis was assayed by measuring the ingestion of 51Cr-tagged sheep erythrocytes. After 3 or 4 days in culture, nonadherent spleen cells (NASC) and B and T lymphocytes from C3H/HeN (LPS-responder) mice produced 92 +/- 27%, 83 +/- 13%, and 147 +/- 33% increases in C3H/HeJ (LPS-hyporesponder) macrophage phagocytic activity, respectively. A similar effect was observed in Balb/c mice. Cell-free supernatant from NASC and B lymphocytes precultured for 2 or 4 days produced a 74 +/- 20% and 157 +/- 42% increase in phagocytosis respectively. At concentrations which have been previously shown to markedly enhance the ability of splenic B lymphocytes to stimulate macrophage glucose metabolism, Escherichia coli K235 LPS (10 micrograms/ml) did not alter the stimulatory effects of any of the splenic lymphocyte populations on macrophage Fc-dependent phagocytosis. These data suggest that B lymphocytes produce a soluble factor(s) which stimulates macrophage phagocytosis. In addition, LPS has different effects on the regulation of macrophage phagocytic activity and metabolism by B lymphocytes.

Animals↗

PubMed1985

Morphometric analysis of medial basal hypothalamic neuronal degeneration in diabetes (db/db) mutant C57BL/KsJ mice: relation to age and hyperglycemia.

Age- and diabetes-related neuronal degenerative changes were morphometrically evaluated in the arcuate (ARC) and ventromedial (VMH) hypothalamic nuclei of control (+/?) and diabetic (db/db) C57BL/KsJ mice between 4 and 16 weeks of age. By 4 weeks of age, (db/db) mice exhibited marked obesity and hyperglycemia relative to controls. An increase in the population of degenerated ARC neurons was detected at 8 weeks of age in (db/db) mice relative to (+/?) animals. By 16 weeks of age, a significant increase in the number of degenerated VMH neurons in (db/db) mice was found, relative to controls. In addition, the neuronal density (neurons/mm2 area of nucleus) of both the ARC and VMH nuclei was found to be depressed in (db/db) mice, relative to controls, by 16 weeks of age. These data suggest that the normal degenerative loss of ARC and VMH neurons that occurs with age in normal mice is enhanced in the (db/db) mouse. These findings suggest that a functional alteration in hypothalamic nuclei which are recognized to modulate autonomic, pancreatic and pituitary activity may be associated with the onset or expression of the diabetic condition in the C57BL/KsJ (db/db) mouse.

Age Factors↗

PubMed1985

Hypoxanthine is the principal inhibitor of murine oocyte maturation in a low molecular weight fraction of porcine follicular fluid.

Studies were carried out to identify and quantify the porcine follicular fluid (PFF) component(s) responsible for inhibition of murine oocyte maturation. A low molecular weight fraction of PFF (less than 1000) was prepared by dialysis and used in all experiments. This PFF fraction contained an inhibitor(s) of mouse oocyte maturation that absorbed maximally in the ultraviolet (UV) range at 250-260 nm. When the PFF fraction was charcoal-extracted, significant loss of absorbance at 250, 260, and 280 nm resulted, which corresponded to loss of inhibitory activity. Four major components of PFF were separated by ion-exchange chromatography and characterized according to their UV spectral characteristics and inhibitory activity. When individual fractions demonstrating identical spectra were pooled and analyzed by high-performance liquid chromatography, the first pooled fraction (A) was found to be impure, but adenine comprised 80% of the UV-absorbing material. Fractions B, C, and D were characterized as pure uracil, hypoxanthine, and 7-methylinosine, respectively. The concentrations of these compounds in PFF were estimated to be 0.06 mM adenine, 0.44 mM uracil, 1.41 mM hypoxanthine, and 0.19 mM 7-methylinosine. Comparison of the potencies of commercial preparations of these compounds established that hypoxanthine is the major inhibitory component of the low molecular weight PFF fraction. Moreover, a commercial preparation of hypoxanthine mimicked the action of PFF on mouse oocyte maturation in that it produced a transient inhibition of oocyte maturation that was significantly potentiated by follicle-stimulating hormone and dibutyryl cyclic adenosine monophosphate. When the inhibitory efficacies of purine and pyrimidine bases and nucleosides were compared, their relative potencies in decreasing order were purine bases greater than purine nucleosides greater than pyrimidine bases = pyrimidine nucleosides. We conclude that hypoxanthine is the predominant low molecular weight component of PFF that inhibits mouse oocyte maturation but that other purines/pyrimidines may also play a role in vivo in maintaining meiotic arrest.

Animals↗

PubMed1985

Hypoxanthine and adenosine in murine ovarian follicular fluid: concentrations and activity in maintaining oocyte meiotic arrest.

The concentrations of hypoxanthine and adenosine in ovarian follicular fluid were estimated, using high-performance liquid chromatography, for three groups of mice: 1) pregnant mare's serum gonadotropin (PMSG)-primed mice; 2) PMSG-primed mice 2 h after injection with human chorionic gonadotropin (hCG); and 3) PMSG-primed mice 5 h after injection with hCG. The concentration of hypoxanthine in follicular fluid of Group 1 mice was 2-4 mM and of adenosine was 0.35-0.70 mM. There was no difference in the concentrations of these purines in the follicular fluid of Group 2 mice, in which maturation had been induced with hCG but the samples were taken just before germinal vesicle breakdown (GVBD). Therefore, a decrease in the concentrations of these purines does not appear to induce GVBD. A significant decrease in the concentrations of hypoxanthine and adenosine was observed in the follicular fluid of Group 3 mice in which GVBD had already occurred. This decrease was probably a result of an increase in follicular fluid volume. Adenosine had a significant, but transient, effect in maintaining both cumulus cell-enclosed and denuded oocytes in meiotic arrest; all oocytes had undergone GVBD by 100 min incubation in 1 mM adenosine. When GVBD was assessed after 3 h culture, concentrations up to 5 mM adenosine failed to maintain meiotic arrest. In contrast, hypoxanthine (2-5 mM) had a dose-dependent effect in maintaining both cumulus cell-enclosed and denuded oocytes in meiotic arrest that was sustained up to 24 h. Cumulus cell-enclosed oocytes were always more sensitive to hypoxanthine than were denuded oocytes. There was a strong synergistic effect of adenosine and hypoxanthine in maintaining meiotic arrest; 4 mM hypoxanthine and 0.75 mM adenosine maintained more than 95% of the oocytes in meiotic arrest for culture periods up to 24 h. This action was completely reversible by withdrawal of the purines. It is hypothesized that the synergistic effect of these purines may result both by promoting cyclic adenosine monophosphate synthesis (adenosine), and by preventing its hydrolysis (hypoxanthine).

Adenosine↗

PubMed1985

Pulmonary macrophage function during experimental cytomegalovirus interstitial pneumonia.

Since cytomegalovirus (CMV) infections may alter host defense against a variety of pathogens, phagocytosis, oxygen uptake, and H2O2 release by pulmonary macrophages obtained from guinea pigs with acute CMV interstitial pneumonia were evaluated. Experimental animals were inoculated subcutaneously on day zero with 10(7.5) 50% tissue culture infective doses of virulent guinea pig CMV. Control animals received an uninfected salivary gland suspension. The animals were sacrificed on day 7; the tissues were cocultivated for virus isolation, and the lungs were lavaged to obtain pulmonary macrophages. CMV was isolated from buffy coat cells (96%), bone marrow cells (71%), whole lungs (77%), pulmonary macrophages (60%), and pulmonary granulocytes (49%). There was no significant difference between groups at sacrifice in the total number of macrophages obtained by pulmonary lavage or in the phagocytic activity of the macrophages in vitro. However, in CMV-infected animals, the maximum rates of O2 consumption in response to the soluble stimulus, phorbol myristate acetate, and the particulate stimulus, Staphylococcus aureus, were 47 and 55%, respectively, of the rates in uninfected controls. Total macrophage O2 consumption in CMV-infected animals was 32 and 37%, respectively, of control values in response to the same stimuli. In CMV-infected animals, the maximum rates of H2O2 release were 22% of those in simultaneous controls for both stimuli, and total H2O2 release was 30 and 25%, respectively, of that in controls in response to these stimuli. Such alterations in macrophage oxidative function may contribute to superinfection during CMV pneumonia.

Acute Disease↗

PubMed1985

Electrical properties of monolayers cultured from cells of human tracheal mucosa.

Dispersed isolated cells were obtained from human tracheal mucosa by digestion with collagenase. Up to 1.5 X 10(8) cells were obtained per trachea and showed up to 95% viability, as judged by trypan blue exclusion. When grown in culture, the cells formed monolayers after approximately 4 days. Electron microscopy of the monolayers revealed a polarized structure. An apical membrane, containing microvilli and a pronounced glycocalyx, was separated from a relatively unspecialized basolateral membrane by typical tight junctions. Monolayers grown on nucleopore filters showed resistances of 44-1,800 omega. cm2 and transepithelial potential differences of 0.1-7.6 mV. Short-circuit current (Isc) was increased by isoproterenol, prostaglandins E2 and F2 alpha, and bradykinin. The loop diuretic, bumetanide, reduced Isc when added to the basolateral (serosal) side but had no effect from the apical (mucosal) side of the monolayers. Furosemide and MK-196 also inhibited Isc. Mucosal amiloride inhibited Isc. Serosal amiloride or mucosal ouabain had no effect on Isc. Serosal ouabain brought Isc to zero after approximately 15 min.

Amiloride↗

PubMed1985

Antiobesity effects of etiocholanolones in diabetes (db), viable yellow (Avy), and normal mice.

Two metabolites of the adrenal steroid dehydroepiandrosterone (DHEA), 3 alpha-hydroxyetiocholanolone and 3 beta-hydroxyetiocholanolone, were found to have antiobesity properties with respect to both prevention of the development of obesity as well as weight reduction after obesity was established. All of the obesity types studied responded to metabolite therapy to a greater or lesser extent. The more natural obesity seen in certain strains of mice with aging responded most rapidly to the feeding of either metabolite. The effective dosage (0.1%) fed in the diet was only one quarter the dosage required for DHEA to produce the same effect in preventing diabetes symptoms in C57BL/Ks diabetic (db) mutant mice. Unlike DHEA, neither metabolite produced any undesirable estrogenic or androgenic side-effects. 3 alpha-hydroxyethiocholanolone and 3 beta-hydroxyetiocholanolone, formerly considered only as inert end products of steroid metabolism, have beneficial actions in mice with various diabetes-obesity conditions and may be metabolic effectors in their own right.

Animals↗

PubMed1985

Age- and diabetes-related changes in tissue glucose uptake and estradiol accumulation in the C57BL/KsJ mouse.

The effect of the diabetes (db/db) mutation on the age-related changes in glucose uptake and estradiol incorporation in peripheral tissues were investigated in C57BL/KsJ mice between 2 and 16 wk of age. Glucose uptake in the uterus, ovaries, pancreas, lung, liver, heart, kidney, and spleen were markedly increased in diabetic mice after the development of the hyperglycemic condition, as compared with control mice. The age-related increase in glucose uptake observed in control mice was enhanced in hyperglycemic (i.e., greater than or equal to 4 wk of age) animals. In contrast, the diabetes mutation caused a decreased estradiol uptake by the uteri, ovaries, and mesometrial fat pads at 16 wk, while having little effect in nontarget tissues of diabetic mutants. These data indicate that the diabetes mutation enhances glucose uptake, especially in estradiol target tissues (i.e., uterus, ovary), at the same time that estradiol incorporation is depressed. These results suggest that an alteration in glucose utilization by steroid-sensitive reproductive tract tissue may underlie the impaired reproductive ability in these animals. Other peripheral tissues did not demonstrate any remarkable changes in estradiol uptake, but the enhanced carbohydrate metabolism observed may relate to the subsequent age- and diabetes-related changes in tissue structure and function in these animals.

Aging↗

PubMed1985

Increased metabolic efficiency in obese mutant mice.

Several different single gene mutations are known to cause similar diabetes-obesity syndromes in mice. Our studies with two mutations, obese (ob) and diabetes (db) have shown that each syndrome develops similarly. Symptoms include hyperinsulinemia, hyperglycemia, hyperphagia, diabetes, and obesity coupled with similar, and large increases, in the efficiency of food utilization. Even when maintained on 50 percent of normal food intake, mutants still become obese. This increase in metabolic efficiency has been suggested to be due to a failure of mutant mice to thermoregulate. Our studies indicate that any defect in thermoregulation is not severe enough to conserve sufficient calories to account for the large increase in metabolic efficiency observed in each mutant and the increased efficiency seen in mutants must be a result of other mechanisms. More critical studies in both normal and obese mice should lead to information defining the contribution of the many different potential energy saving mechanisms available.

Animals↗

PubMed1984

Diabetes-associated changes in estradiol accumulation in the aging C57BL/KsJ mouse brain.

The effects of aging and diabetes on the uptake and incorporation of [3H]estradiol (E) in various brain areas was analyzed in C57BL/KsJ mice. Control (C; +/?) and diabetic (D; db/db) mice were pulse treated (30 min) with 10 muCi of [3H]E at 1, 2 and 4 months of age and the brains were subsequently microdissected, digested and the amount of incorporated [3H]E assessed. The pituitary and amygdala exhibited the highest levels of [3H]E incorporation of all brain areas, with the hypothalamus, septal nuclei, midbrain, hippocampus, medulla and parietal cortex exhibiting moderate retention levels at one month of age in C animals. All brain areas in D mice had significantly lower incorporation rates than in matchpaired, C animals. An age-related decrease in [3H]E accumulation was observed in all brain regions in both C and D groups, with a significant depression in [3H]E incorporation occurring between 1 and 4 months of age. These data demonstrate that an age-related decrease in [3H]E uptake occurs in most brain areas in the C57BL/KsJ mouse, and that the diabetic condition exacerbates this phenomenon.

Age Factors↗