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Biomedical subjects

D L Coleman

Publications and source records attributed to D L Coleman.

At least 109 records · Page 6Linked to original sources
PubMed1984

Glucose utilization by the mouse brain: influence of age and diabetes.

The effects of diabetes on the age-related changes in glucose utilization by various brain regions were examined in genetically diabetic (db/db) and normal (+/?) C57BL/KsJ mice following a 10 muCi injection of [3H]2-deoxyglucose (2-DOG). Brains were collected from 2 to 16-week-old mice at 30 min postinjection with 2-DOG, and the brain regions isolated by microdissection. Glucose utilization was expressed as mumol/mg/30 min for each brain region from match-paired control +/? and db/db mice. No differences in utilization were seen in brain regions from control and db/db mice at 2 weeks of age. In contrast, the diabetic condition effectively depressed the age-related increase in glucose metabolism associated with maturation in control mice between 4 and 16 weeks of age. Of particular interest was the observation that the pituitary gland of the db/db mice did not demonstrate a maturation-associated increase in glucose utilization typical of +/? mice. By 16 weeks of age, all of the brain regions of db/db mice exhibited a depressed glucose utilization rate as compared with +/? mice. These studies demonstrate that the diabetic condition impairs the normal age-related increase in CNS glucose utilization in the mouse, and suggests that decreased glucose utilization may be causally related to diabetes-associated, CNS and peripheral neuropathy.

Age Factors↗
PubMed1984

Effect of intravenous recombinant alpha-2 interferon on monocyte Fc-dependent phagocytosis in patients with malignant melanoma.

Recombinant alpha interferons (IFN-alpha) have diverse effects on the immune response. Alpha IFNs have been shown to increase the number of monocyte Fc receptors and Fc dependent phagocytosis in vitro. Therefore, we prospectively evaluated Fc-dependent phagocytic activity in a group of 14 patients with Stage III melanoma receiving from 10 to 100 X 10(6) u of recombinant DNA-produced alpha-2 interferon (IFN-alpha 2) five days a week for four weeks. Monocyte Fc-dependent phagocytosis (FcDP) was assayed by measuring the ingestion of 51Cr-labeled, IgG-coated sheep erythrocytes before, and on Days 2, 5, and 19 of IFN therapy. Each patient was simultaneously compared with the same unmatched normal controls during the assay period. Monocyte FcDP was unchanged in 8/14 patients on each of the three sampling days. Increases in FcDP occurred in 4/14 patients on Day 2 and only 1/14 on Day 19. Recombinant DNA-produced IFN-alpha 2 did not persistently augment monocyte FcDP irrespective of the dose administered. Moreover, there may be untoward effects on monocyte FcDP in vivo from intravenous administration of high dose IFN-alpha 2 since a distinct, but statistically insignificant (p = 0.06) trend of inhibition of FcDP by Day 19 of therapy was observed. Monocyte FcDP activity of normal controls fluctuated from day to day. The intrinsic variability in monocyte FcDP as assessed by this technique may conceal an effect(s) of IFN preparations in vivo. Additional studies are needed to further define the effects of purified IFN preparations on monocyte and tissue-derived macrophage effector functions.

Cloning, Molecular↗
PubMed1984

Improved system for floor cleaning in health care facilities.

A new system has been developed for sanitizing floors in hospitals; this system replaces the traditional procedure of daily dusting and wet mopping with a disinfectant-detergent solution and periodic buffing . This new system relies on a sequence of procedures consisting of dust mopping using a chemically treated dust mop, machine buffing of a sprayed-on polymer treatment, and a second dust mopping . The effectiveness of the procedures was evaluated by means of surface sampling for bacterial contamination and air sampling for airborne bacteria and dust. The level of bacterial contamination on the floors was reduced by 93.6% by using the new system, compared with 79.8% by using the conventional process of dust mopping and wet mopping with a disinfectant solution. The levels of airborne bacteria during and after the individual procedures did not vary significantly from the initial level (123.6 CFU/per m3 of air). A survey of representative colonies from air samples revealed staphylococci, gram-positive bacilli, gram-positive diplococci, yeast cells, and infrequent gram-negative rods. The distribution at the conclusion of the sanitizing process was similar to that at the outset. Similarly, the levels of airborne dust measured during and after the individual procedures did not vary significantly from the initial level. When compared with the traditional method of cleaning by wet mopping , the new method was significantly more effective in removal of microbial contamination and required less labor.

Air Microbiology↗
PubMed1984

Electrical properties of dog tracheal epithelial cells grown in monolayer culture.

Epithelial cells from dog trachea, when grown in tissue culture, formed confluent monolayers 5-6 days after plating. After 8-10 days, domes [mean diam 356 +/- (SE) 53 micron] appeared in monolayers grown in collagen-coated flasks. When grown on polycarbonate filters coated with collagen, a detectable resistance (greater than 5 omega X cm2) and transepithelial potential difference (PD) (greater than 0.1 mV) developed 6 days after plating and increased to approximately 15 omega X cm2 and 15 mV at 10 days. Serosal ouabain (10(-4) M) abolished PD and short-circuit current (Isc). Luminal ouabain had no effect. Luminal amiloride (10(-4) M) and serosal bumetanide (10(-4) M) each decreased PD and Isc. However, a combination of both of these drugs did not abolish Isc. Isoproterenol (10(-5) M), dibutyryl adenosine 3',5'-cyclic monophosphate (10(-3) M), vasoactive intestinal peptide (10(-7) M), prostaglandin (PG) E2 (10(-5) M), PGF2 alpha (10(-5) M), and bradykinin (10(-5) M) each increased PD and Isc. Thus these monolayer cultures maintain electrical properties resembling those of the original tissue. This preparation may prove useful for the study of water and ion transport by airway epithelia.

Amiloride↗
PubMed1984

Correlation between serial pulmonary function tests and fiberoptic bronchoscopy in patients with Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

The records of 9 adult male patients with the acquired immune deficiency syndrome (AIDS) and biopsy-proved Pneumocystis carinii pneumonia were reviewed to determine the correlation between serial pulmonary function tests and the presence or absence of Pneumocystis organisms in subsequent bronchoscopy specimens. At diagnosis, total lung capacity (TLC) or vital capacity (VC) was abnormally low in 4 patients (44%) and diffusing capacity (DLCO) was abnormally low in 8 patients (89%). The ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) was elevated in all patients. After 21 to 47 days of specific therapy for Pneumocystis pneumonia, changes in DLCO, TLC, VC, and FEV1/FVC did not correlate with the presence or absence of Pneumocystis organisms in bronchoscopy specimens from 7 patients. However, changes in DLCO 105 to 258 days after diagnosis seemed to correlate with the late response to treatment in 6 patients. These results suggest that decisions to terminate specific therapy for Pneumocystis pneumonia in patients with AIDS should not be based on short-term changes in pulmonary function.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Correlation between gallium lung scans and fiberoptic bronchoscopy in patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

We retrospectively examined the sensitivity and specificity of gallium lung scans for detecting Pneumocystis carinii pneumonia in 22 patients with known or suspected acquired immune deficiency syndrome. Correlations were made between bronchoscopic results and gallium scan findings interpreted using a simple system (normal or abnormal) and a graded score (1 to 4). All 12 patients with Pneumocystis had abnormal scans by both interpretations (sensitivity, 100%). Five of these 12 patients had normal arterial PO2 values, chest roentgenograms, or both. In the 10 patients without Pneumocystis, scans were read as abnormal in 8 using the simple system (specificity, 20%) but were abnormal in only 1 using the grading system (specificity, 90%). Five patients with Pneumocystis pneumonia had scans and bronchoscopy after treatment; neither method of interpretation correlated with the presence of organisms. We conclude: (1) gallium scanning is a sensitive initial diagnostic test in patients with suspected Pneumocystis pneumonia; (2) a graded scoring system improves specificity; (3) an abnormal gallium scan (3 or greater) in patients with suspected Pneumocystis pneumonia is an indication for biopsy, even when the PO2 and/or chest roentgenogram are normal.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Therapeutic effects of dehydroepiandrosterone metabolites in diabetes mutant mice (C57BL/KsJ-db/db).

Dehydroepiandrosterone (DHEA) fed at 0.4% in the diet is known to exert strong antihyperglycemic effects in C57BL/KsJ genetically diabetic (db/db) mice. Three of the major metabolic products of DHEA; DHEA sulfate, alpha-hydroxyetiocholanolone (alpha-ET), and beta-hydroxyetiocholanolone (beta-ET) when fed at 0.1% in the diet, and one putative product, 17 beta-estradiol, when fed at 0.005% also prevented the development of severe diabetes while having little effect on the amount of food eaten or the rate of weight gain. When suboptimal doses (5-20 micrograms/week) of estradiol were injected in combination with diets containing either alpha-ET or beta-ET, marked potentiating effect was noted, normalization of the hyperglycemia being produced with as little as 0.025% of beta-ET and 0.05% of alpha-ET. The ability of the etiocholanolones to maintain islet integrity and prevent the development of most diabetes symptoms suggests that these metabolites are not merely inactive end products of steroid metabolism, but are physiological effectors in their own right.

Androsterone↗
PubMed1984

Effect of genetic background on the therapeutic effects of dehydroepiandrosterone (DHEA) in diabetes-obesity mutants and in aged normal mice.

Dehydroepiandrosterone (DHEA) was fed at 0.1-0.4% in the diet to genetically diabetic (db/db) or obese (ob/ob) C57BL/KsJ (BL/Ks) or C57BL/6J (BL/6) mice. Treatment of BL/Ks-db/db or ob/ob mice with 0.4% DHEA prevented hyperglycemia, islet atrophy, and severe diabetes associated with this inbred background, but did not affect weight gain and food consumption. Homozygous obese (ob) or diabetes (db) mice on the BL/6 background were more sensitive to DHEA, and the mild, transient hyperglycemia associated with ob or db gene expression on the BL/6 inbred background could be prevented by 0.1% DHEA. Both body weight and food consumption were decreased in BL/6 mutants maintained on 0.1% DHEA whereas this effect was not seen in BL/Ks mutants fed up to 0.4% DHEA. Early therapy with 0.4% DHEA, initiated at 2 wk of age, prevented the development of most diabetes symptoms and decreased the rate of weight gain in pups of all genotypes. In addition to therapeutic effects on both obese mutants, DHEA effected significant changes in an aging study using normal BL/6 female mice. Four weeks of DHEA treatment initiated at 2 yr of age improved glucose tolerance and at the same time reduced plasma insulin to a "younger" level. This suggests that DHEA may act in insulin-resistant mutant mice and in aging normal mice to increase the sensitivity to insulin.

Aging↗
PubMed1984

Enhancement of macrophage immune and nonimmune receptor-mediated phagocytosis by a low molecular weight soluble factor from resident thymocytes.

Macrophage phagocytic activity is regulated in part by products of activated T lymphocytes. We previously reported that a heat-stable soluble factor derived from resident (nonactivated) thymocytes increases murine peritoneal macrophage Fc-dependent phagocytosis. In the present study, we further investigate the effect of the thymocyte factor on immune and nonimmune receptor-mediated phagocytosis, Fc receptor expression, and its approximate m.w. After 4 days of incubation, cellfree thymocyte supernatant produced a mean (three experiments) 2.10-, 2.08-, and 1.97-fold increase in macrophage phagocytosis of C3-, IgG-, and tannic acid-treated erythrocytes, respectively. Macrophage IL 1 production was not enhanced by a similar concentration of thymocyte supernatant. The thymocyte factor(s) increased the number of IgG2a Fc receptors (FcRI) from 2.4 x 10(5) to 3.8 x 10(5) receptor sites per macrophage. The number of Fc receptors that bind IgG1 and IgG2b (FcRII) was not altered. The soluble factor(s) that increased Fc-mediated phagocytosis passed through both 6000- to 8000-dalton and 2000-dalton cutoff dialysis membranes and eluted from a Sephadex G-25 Fine column over a m.w. range of 200 to 1000 daltons, with a peak activity at 450 daltons. These data suggest that resident thymocytes enhance macrophage phagocytosis of opsonized and nonopsonized particles through the elaboration of a low m.w. substance(s).

Animals↗
PubMed1983

Temporal changes in pancreatic islet composition in C57BL/6J-db/db (diabetes) mice.

Temporal changes in non-B cell populations were determined during the period of B cell hyperplasia in diabetes-resistant C57BL/6J mice. Pancreases from normal and db/db mice between 3 and 20 weeks of age were stained immunocytochemically for glucagon, somatostatin and pancreatic polypeptide (PP), and changes in A, D and PP cell volume densities quantified by image analysis. Further, islet volumes, D cell volumes and actual D cell numbers per islet were determined by analysis of serial sections through entire islets. The volume of db/db islets was three- and ten-fold elevated above normal by 8 and 20 weeks, respectively, due mainly to B cell hyperplasia. D cell volume density exhibited a transient increase during the initial phase of B cell hyperplasia, but then showed a gradual reduction; the average number and absolute volume of D cells per islet was comparable in db/db and normal islets from older mice. In contrast, PP cell volume density remained stable throughout, suggesting that this cell type kept pace with B cell hyperplasia. A cells showed a reduced volume density throughout and were distinguished from other islet cells which all responded positively to a degree, albeit non-coordinately, to the mitogenic stimulus exerted by db gene expression. The finding that A cells shared with certain neuroectodermally-derived cell types a differentially high concentration of sn-glycerol-3-phosphate dehydrogenase further underscored the uniqueness of the A cell from other cell types.

Aging↗
PubMed1983

Lessons from studies with genetic forms of diabetes in the mouse.

Genetically defined animal models of diabetes have many advantages over models in which the genetic component has not been established. Such models permit predictable numbers of normal and afflicted animals, differing by only a single gene, to be produced at will. Maintenance of these individual mutations in inbred strains of mice permits an evaluation of any gene-host interactions that act by modifying the severity of the diabetic condition. These genetic models provide precision tools for research in which the mutant gene itself, the inbred background, and the environment can be manipulated at will. In addition there is sufficient knowledge about the arrangement of individual genes in chromosomes in the mouse to permit one to identify, and use, closely linked markers in order to predict with confidence the mice destined to become diabetic. Such studies on the preclinical stages are of utmost importance and cannot be undertaken conveniently in any other model. Our studies with genetic mouse models have established that there are at least six genes in the mouse that can cause diabetes and obesity syndromes. The severity of the diabetes produced depends on the interaction of the mutant gene with the host inbred background as well as with other environmental factors. Establishing the nature of these interactions and the possible primary lesions involved in each genetic syndrome should have major ramifications in studies dealing with human diabetes.

Animals↗
PubMed1983

Latamoxef (moxalactam) kinetics in volunteers studied by a specific HPLC assay technique.

Pharmacokinetic parameters were calculated from plasma and urine latamoxef ('Moxalactam') levels determined by HPLC assay after single and multiple intramuscular (im) and single intravenous (iv) doses of 500 mg given to eight healthy volunteers. After im administration, systemic bio-availability was 92% after both the first and sixth doses. Peak plasma concentration was 18 mg/l (first dose) and 22 mg/l (sixth dose), reached at 1.2 h and 1.3 h respectively. The terminal phase half-lives were 2.5 h and 2.7 h respectively. After iv administration, the initial phase plasma half-life was 0.23 h and the terminal phase half-life, 2.4 h. Plasma clearance was 87.0 ml/min. The steady state distribution volume was 210 ml/kg. After iv administration, 72% of the dose was found in the urine in the first 24 h. Urinary clearance was 66 ml/min (iv dose) and 63 ml/min (sixth im dose). Most systemic infections will permit eight hourly dosing with 500 mg im or iv. Many urinary infections will be best treated with im administration, rather than iv administration.

Adult↗
PubMed1983

Influence of dietary carbohydrate on the induction of diabetes in C57BL/KsJ-db/db diabetes mice.

Genetically diabetic C57BL/KsJ-db/db and normal littermate mice of both sexes were fed one of nine defined diets from weaning. The objective was to study dietary carbohydrate interaction with the diabetogenic genes through isocaloric substitution of protein for carbohydrate (either sucrose or dextrin starch) at concentrations of 0, 8, 24, and 60%. In addition, at 60% concentration, the effect of type of carbohydrate (e.g., glucose, fructose, sucrose or dextrin starch) on the deterioration of endocrine pancreatic structure and function was analyzed. The carbohydrate-free diet produced the greatest survival to 1 year of age and allowed the expression of an obesity syndrome uncomplicated by severe hyperglycemia or by extensive necrosis of pancreatic beta cells and islet atrophy. Those diets containing intermediate levels of carbohydrate (8 or 24% of sucrose or dextrin), or 60% dextrin starch, in comparison to diets containing 60% refined carbohydrates, extended life span and produced a more protracted pathogenesis, but were unable to circumvent eventual severe hyperglycemia and islet destruction. The diets containing 60% glucose, fructose, or sucrose all led to the rapid induction of diabetes. Thus, pathogenesis entails an interaction between dietary carbohydrate, the db gene, and other diabetes-predisposing genes in the genome.

Animals↗
PubMed1983

Diagnostic utility of fiberoptic bronchoscopy in patients with Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome.

The records of 35 adult male patients with suspected Pneumocystis carinii pneumonia and the acquired immune deficiency syndrome were reviewed to determine the diagnostic utility of fiberoptic bronchoscopy. Twenty-two of the 24 patients (92%) shown to have Pneumocystis pneumonia were diagnosed by bronchoscopy; 20 patients were diagnosed after 1 bronchoscopy and 2 patients after 2 bronchoscopies. The sensitivity of bronchoscopy specimens for diagnosing Pneumocystis pneumonia was 79% for transbronchial biopsies (19 of 24), 78% for transbronchial biopsy touch preparations (7 of 9), 55% for bronchial washings (11 of 20), and 39% for bronchial brushings (7 of 18). The overall sensitivity of fiberoptic bronchoscopy was 85% (22 positive of 26 total bronchoscopies). Complications, occurring during 6 of the 37 bronchoscopies, were slight hemoptysis (1 patient), fever (2 patients), septic shock (1 patient), and pneumothorax (2 patients). Fiberoptic bronchoscopy is a safe and effective procedure for making the early diagnosis of Pneumocystis carinii pneumonia in adult male patients with the acquired immune deficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Enhancement of macrophage Fc-dependent phagocytosis by resident thymocytes: effect of a unique heat-stable lymphokine.

Lymphocytes, activated by lectins or specific antigens, have been shown to enhance macrophage phagocytosis through the elaboration of a heat-labile soluble factor(s). Recent evidence from our laboratory revealed that resident (nonactivated) murine thymocytes and splenic lymphocytes increase peritoneal macrophage glucose metabolism through the elaboration of a heat-stable soluble factor(s). Therefore, we investigated the effect of resident lymphocyte subpopulations on macrophage Fc-dependent phagocytosis. Thioglycollate-elicited and resident peritoneal macrophages from BALB/c mice were cultured in serum-free media with syngeneic resident thymocytes or splenic T lymphocytes. Macrophage Fc-dependent phagocytosis was assayed by measuring the ingestion of 51CrSHEA. After 4 days in vitro, resident thymocytes produced a mean 160 (+/- 31) and 136% (+/- 22) increase in Fc-dependent phagocytosis by thioglycollate-elicited (thio-macrophages) and resident peritoneal macrophages, respectively. Splenic T lymphocytes increased thio-macrophage phagocytosis by 112% (+/- 41) under similar conditions. Macrophage Fc-dependent phagocytosis was increased after 24 hr of co-culture by supernatant derived from resident thymocytes and could be further enhanced by supernatant from Con A-activated thymocytes. Supernatant from guinea pig embryo fibroblasts did not increase macrophage phagocytosis. The soluble factor(s) was produced by resident thymocytes after 24 hr of preculture. This factor was active despite heating at 100 degrees C for 30 min whereas the effect of Con A-activated thymocyte supernatant was heat-labile. The stimulatory effect of resident thymocyte supernatant was not observed when the macrophages and supernatant were cultured in 2% FCS. In contrast to the factor(s) produced by resident thymocytes, the factor(s) in FCS that increased phagocytosis was heat-labile. These data suggest thymocytes and splenic T lymphocytes promote macrophage Fc-dependent phagocytosis in the absence of antigenic or lectin stimulation. This previously unrecognized effect of resident thymocytes is due to a unique heat-stable soluble factor(s) that is concealed in the presence of serum.

Animals↗