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Biomedical subjects

G S Davis

Publications and source records attributed to G S Davis.

At least 19 recordsLinked to original sources
PubMed2001

The effects of genetic selection on production parameters of single comb White Leghorn hens.

Four commercial table egg genetic stocks consisting of the Ottawa Control Strains 5, 7, and 10 (CS5, CS7, and CS10) and the 1993 H&N "Nick Chick" (CCS) were housed in the same environment and compared for production characteristics. These birds were housed in an environmentally controlled laying facility with trideck cages. Feed consumption, egg production, and mortality were monitored daily and compiled every 28 d. The study was conducted for two egg production cycles, including the molt period. Body weight was progressively lower for the more modern strains with CS5 being the heaviest and CCS maintaining the smallest body weight throughout the production periods. The CCS had the highest (P < 0.0001) hen-day production rate, which resulted in the greatest daily egg mass among the strains. The CCS consumed the greatest amount of feed and exhibited the highest gross egg income among the strains. We concluded that genetic selection has improved production parameters in commercial layers as determined by measurements in this study.

Animals↗
PubMed2001

Maternal dietary iodide influences turkey embryonic thyroid function.

An experiment was designed to examine a mechanism to improve embryonic survival following maternal thyroid hormone manipulation. Commercial turkey breeder hens were fed diets containing supplemental iodide to mimic changes in the maternal thyroid output during an egg production cycle (32 to 48 wk of age). Dietary iodide treatment depressed maternal blood thyroxine (T4) concentrations in a time-dependent manner. Dietary iodide depressed maternal blood 3, 5, 3'-triiodothyronine (T3) levels across all times examined. The maternal dietary treatment increased embryonic blood concentrations of T4 at 25 to 28 d of incubation but depressed blood concentrations of T3 only at 27 d of incubation. In a second trial, the same response was noted in maternal blood when the hens were fed additional iodide with no corresponding effects on T3 concentrations. The iodide treatment decreased embryonic T4 concentrations in the second trial as well but in a time-dependent manner. Iodide accelerated the increase in T4 concentrations coincidental with earlier pipping in eggs from iodide-fed dams compared with controls. The data indicate that the embryonic thyroid function during hatching is dependent upon the maternal thyroid in turkey dams, even though the embryo develops outside the maternal body.

Animal Feed↗
PubMed2001

Lymphocytes, lymphokines, and silicosis.

Silicosis is characterized by mononuclear cell aggregation with mineral particles and fibrosis. Lymphocytes are abundant in these lesions. We exposed inbred strains of mice to a respirable aerosol of cristobalite silica (70 mg/m3, 5 h/d, 12 d) or shamair. Silicosis evolved over months after exposure. The silica-exposed mice showed the accumulation of lymphocytes in alveolar spaces (seen in bronchoalveolar lavage), in lung parenchymal lesions and nodules, and in enlarged bronchial-associated lymphoid tissues and thoracic lymph nodes. The lung lymphocytes were predominantly CD4+ T cells, but numerous CD8+ T cells, natural killer cells, and CD4- gammadelta-TCR+ T cells were present as well. Interferon-gamma (IFN-gamma) production was upregulated, suggesting a THelper-1-like response in silicosis. In silicotic lung tissue, mRNA transcripts for the macrophage-derived cytokines IL-12 and -18 were increased. IFN-gamma gene-deleted mice (C57Bl/6-Ifngtm1 Ts) exposed to silica developed less extensive silicosis and less lung collagen accumulation than wild-type mice. We hypothesize that there is a reiterative amplification cycle in which macrophages with silica may produce cytokines, such as IL-12 and -18, that attract and activate lymphocytes. These activated lymphocytes may then produce additional mediators that in turn attract and activate an expanded secondary population of macrophages. IFN-gamma would be a likely cause of macrophage activation in this cycle. More work is needed to understand the biological events that lead from the inhaled dust to the scarred lung, and to clarify the role of lymphocytes in this process.

Air Pollutants, Occupational↗
PubMed2000

Rapid early onset lymphocyte cell death in mice resistant, but not susceptible to Leishmania major infection.

Leishmania major (Lm) infection in mice is a prototypical model for the role of immune deviation in disease resistance. Resistant strains of mice develop a Th1 response to Lm infection, distinguished by secretion of IL-12 and interferon gamma. In contrast, susceptible strains display sustained IL-4 expression characteristic of a Th2 response. However, when mechanisms of cell death are blocked, mice display a susceptible phenotype even in the presence of a strong Th1 response, suggesting that cell death, and not cytokine bias, may be an important factor in disease resistance. Here, we investigated this hypothesis by comparing lymphocyte cellularity, cell death and Fas expression in resistant CBA and susceptible BALB/c mice during the course of Lm infection. We found that delayed onset of cell death and late Fas induction correlated with massive lymphocyte accumulation and susceptibility to leishmaniasis, while early cell death and rapid Fas induction occurred in resistant mice.

Animals↗
PubMed2000

Quantitative image analysis of lung connective tissue in murine silicosis.

Pulmonary fibrosis is a disabling consequence of many lung diseases but is difficult to quantify. Lucifer yellow CH fluorescent dye (LY) appears to stain connective tissue matrix macromolecules selectively. Laser scanning confocal microscopy can quantify the intensity of fluorescence and determine the area of fluorescent material. We hypothesized that the abundance of lucifer yellow-stained matrix macromolecules in lung tissue sections could be measured by laser scanning confocal microscopy, would reflect differences between varying degrees of pulmonary fibrosis, and could be compared directly to biochemical measurements of lung collagen. We exposed C57B1/6 and 129 strains of mice by aerosol to cristobalite silica (70 mg/m3, 12 days, 5 hours/day) or sham-air and examined them 2 and 16 weeks after exposure. The area of LY-stained matrix in tissue sections was quantitated by laser scanning confocal microscopy, and total lung collagen was measured biochemically as hydroxyproline (OH-proline). The LY-stained connective tissue matrix appeared as bright linear bands in the alveolar septae, and was increased significantly by image analysis in C57B1/6 and 129 mice with silicosis 16 weeks after exposure. Total lung OH-proline was significantly increased in silica-exposed mice from both stains at both time points. Comparing all 8 groups, there was a significant linear correlation between the average area of connective tissue measured by LY stain and the total OH-proline per lung measured by chemical analysis (r = .72, P = .042). LY staining and confocal microscopy with image analysis offers a rapid technique for quantitative measurements of the extent of pulmonary fibrosis.

Animals↗
PubMed2000

The effects of long-term caging and molt of Single Comb White Leghorn hens on heterophil to lymphocyte ratios, corticosterone and thyroid hormones.

Two commercial strains of 18-wk-old Single Comb White Leghorn (SCWL) hens, HyLine W-36 and DeKalb XL, were housed six hens per cage in layer cages at two densities (361 and 482 cm2 per bird) with two replications each per strain and density combination. The high density treatment contained 24 hens per replication, and the low density treatment contained 18 hens per replication. Egg production was measured during the first egg production cycle, a molt (fast) period, and the first 4 wk of the second lay cycle (20 to 68 wk of age). Blood samples were obtained from six hens from each replicate in each strain and density combination (total of 48) at 20, 26, 34, 43, 51, 62, 64, and 68 wk of age. In addition, blood samples were obtained in a random order from hens in each cage, and the sequence of sampling was recorded (1 to 6). Blood smears were made, from which heterophil to lymphocyte ratios (H:L) were determined. Radioimmunoassays were conducted to determine levels of plasma corticosterone (CS), 3,5,3'-triiodothyronine (T3), and thyroxine (T4). The results indicated that strain did not affect percentage hen-day egg production (%HDP). Strain and cage density did not affect H:L, T3, T4, or CS. However, these parameters were affected by bird age, which was related to the egg production cycle. Plasma CS significantly (P < or = 0.001) increased during peak %HDP at 26 wk and 64 wk during the molt (fast), and H:L significantly (P < or = 0.001) increased during the molt (fast) at 64 wk. The sequence in which blood samples were obtained, from hens within a cage in sampling order, also increased plasma CS. The CS was significantly (P < or = 0.001) elevated in the third, fifth, and sixth hens from which blood samples were drawn. Plasma T3 and T4 changed during the production cycle. The T3 was significantly (P < or = 0.0001) depressed during peak egg production at 26 wk and during the molt (fast) at 64 wk when compared with the other time periods. Plasma T4 was depressed (P < or = 0.0001) at 51 wk and was elevated (P < or = 0.0001) at 64 wk during the molt (fast). The physiological and metabolic parameters of the different hen strains and cage densities were similar during egg production. However, CS, T3, T4, and H:L changed with age in relation to the egg production cycle. In addition, the physiological demands of peak egg production and molt (fast) appeared to be similar.

Aging↗
PubMed2000

Interferon-gamma production by specific lung lymphocyte phenotypes in silicosis in mice.

We recently described overproduction of interferon (IFN)-gamma by lung lymphocytes in mice with silicosis (11% of cells in air-control versus 19% of cells from silica-exposed mice; Davis and colleagues, Am. J. Respir. Cell Mol. Biol. 1999;20:813-824). We hypothesized that the increased IFN-gamma production might be due to selective enrichment of one lymphocyte phenotype. To test this hypothesis, small mononuclear cells from lung digest preparations of mice exposed 4 mo previously to cristobalite silica (70 mg/m(3), 12 d, 5 h/d) or to sham-air were stained for intracellular cytokines and surface antigen phenotypes, and examined by flow cytometry. Air-sham mouse lung digests included CD4(+) (16%) and CD8(+) (6%) T cells, gammadelta T-cell antigen receptor (TCR)(+) CD4(-)CD8(-) T cells (3%), natural killer (NK) cells (15%), B cells (6%), and macrophages (12%). The total number of lung lymphocytes was increased 1.7-fold in silicosis, but the phenotype frequencies did not change significantly. In the control lungs IFN-gamma was produced by three major phenotypes of lymphocytes: 5% of CD4(+) T cells, 5% of gammadelta-TCR(+) CD4(-)CD8(-) T cells, and 2% of NK cells. The percentage of each type producing IFN-gamma was increased 2- to 3-fold in silicosis. When multiplied by cell number, the increased percentages yielded a 3- to 5-fold increase in the total number of each IFN- gamma-producing phenotype in the lung. Our results demonstrate no selective phenotype enrichment but upregulated IFN-gamma production by at least three lymphocyte phenotypes. IFN-gamma may be an important signal driving lymphocyte differentiation and macrophage activation in silicosis.

Animals↗
PubMed1999

gamma delta+ T cells regulate major histocompatibility complex class II(IA and IE)-dependent susceptibility to coxsackievirus B3-induced autoimmune myocarditis.

Coxsackievirus B3 (CVB3) infection induces myocardial inflammation and myocyte necrosis in some, but not all, strains of mice. C57BL/6 mice, which inherently lack major histocompatibility complex (MHC) class II IE antigen, develop minimal cardiac lesions despite high levels of virus in the heart. The present experiments evaluate the relative roles of class II IA and IE expression on myocarditis susceptibility in four transgenic C57BL/6 mouse strains differing in MHC class II antigen expression. Animals lacking MHC class II IE antigen (C57BL/6 [IA+ IE-] and ABo [IA- IE-]) developed minimal cardiac lesions subsequent to infection despite high concentrations of virus in the heart. In contrast, strains expressing IE (ABo Ealpha [IA- IE+] and Bl.Tg.Ealpha [IA+ IE+]) had substantial cardiac injury. Myocarditis susceptibility correlated to a Th1 (gamma interferon-positive) cell response in the spleen, while disease resistance correlated to a preferential Th2 (interleukin-4-positive) phenotype. Vgamma/Vdelta analysis indicates that distinct subpopulations of gamma delta+ T cells are activated after CVB3 infection of C57BL/6 and Bl.Tg.Ealpha mice. Depletion of gamma delta+ T cells abrogated myocarditis susceptibility in IE+ animals and resulted in a Th1-->Th2 phenotype shift. These studies indicate that the MHC class II antigen haplotype controls myocarditis susceptibility, that this control is most likely mediated through the type of gamma delta T cells activated during CVB3 infection, and finally that different subpopulations of gamma delta+ T cells may either promote or inhibit Th1 cell responses.

Animals↗
PubMed1999

Expansion of interferon-gamma-producing lung lymphocytes in mouse silicosis.

Silicosis is characterized by mononuclear cell inflammation with macrophage activation, accumulation of lymphocytes, and fibrosis. Interferon-gamma (IFN-gamma) is a lymphocyte cytokine with broad effects, particularly macrophage activation. Mice exposed to an aerosol of cristobalite silica (70 mg/m3, 12 d, 5 h/d) developed diffuse pulmonary pathologic changes with macrophage, lymphocyte, and neutrophil recruitment, and increased lung collagen. IFN-gamma messenger RNA (mRNA) was more abundant by semiquantitative reverse transcription-polymerase chain reaction in the lungs of silica-exposed mice than in control animals. IFN-gamma mRNA transcripts were detected by in situ hybridization with digoxigenin-labeled complementary DNA probes in normal mouse lung tissue within bronchial-associated lymphoid tissues (BALT). In silica- exposed mice, mononuclear cells with IFN-gamma mRNA were more numerous in the silicotic lesions and enlarged BALT structures. Lung-cell suspensions were prepared by enzyme digestion, stained with fluorescent-labeled antibodies against intracellular cytokines, and enumerated by flow cytometry. The percentage of cells producing IFN-gamma was increased in silicotic mice (19% versus 11%). Interleukin (IL)-4 mRNA transcripts were less abundant in the lung tissue from silica-exposed mice than in control mice. Cells staining for IL-4 mRNA were found rarely in either the air-sham or the silica-exposed mouse lungs, and almost all appeared to be within BALT structures. Approximately 3% of cells stained for IL-4 in the digested lungs from both groups. Similar cytokine patterns were observed in mediastinal lymph node/thymus and spleen tissues. The augmented IFN-gamma response, with IL-4 unchanged or decreased, in the lung lesions and lymphoid tissue of mice with silicosis suggests a Th-1-like lymphocyte-mediated immune-inflammatory response.

Aerosols↗
PubMed1998

Silicosis in mice: effects of dose, time, and genetic strain.

Experimental silicosis allows study of the mechanisms of lung injury, inflammation, and fibrosis. Inbred mice are an attractive species in which to study these mechanisms because of recent progress in murine immunology, molecular biology, and genetics. We exposed mice to an aerosol of silica and examined the effects of exposure dose, the evolution of disease features over time, and the variation in responses among four inbred strains. In C3H/HeN mice incremental cumulative exposure doses of cristobalite silica caused increased initial lung dust burden 12 to 16 weeks post-exposure, progressively intense pathological responses, and increased total lung collagen (hydroxyproline). The histopathological changes and total lung collagen increased progressively over time after exposure. We compared the features of silicosis in four strains of inbred mice selected for common use or immunologic reactivity 16 weeks after aerosol inhalation exposure to crystalline cristobalite silica (70 mg/m3, 5 hours/day, 12 days). C3H/HeN mice demonstrated histopathological silicotic lesions and enlarged intrapulmonary lymphoid tissue, and increased lung wet weight, bronchoalveolar lavage (BAL) recovery of macrophages, lymphocytes, and neutrophils, and total lung collagen (hydroxyproline). BALB/c mice developed slight pulmonary lesions; MRL/MpJ mice demonstrated prominent pulmonary infiltrates with lymphocytes; New Zealand Black mice developed extensive alveolar proteinaceous deposits, inflammation, and fibrosis. Our findings demonstrate orderly dose-time-response relationships, and a substantial variation of responses among inbred strains of mice. This model should prove valuable for future experimental interventions into the mechanisms of silicosis.

Administration, Inhalation↗
PubMed1998

Persistent overexpression of interleukin-1beta and tumor necrosis factor-alpha in murine silicosis.

The cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNFalpha), derived from macrophages and other cells, may promote mononuclear cell inflammation and fibrosis in pulmonary silicosis. C3H/HeN mice were exposed to control air or to an aerosol of 70 mg/m3 cristobalite silica for 5 h/d for 12 days and examined at 2 and 16 weeks after exposure. This exposure resulted in murine silicosis, as manifested by focal mononuclear cell accumulations, diffuse interstitial fibrosis, lymphoid tissue enlargement, recruitment of inflammatory cells into BAL fluid, and increased total lung collagen. Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) with designed primers and membrane hybridization with biotinylated cDNA probes were used to assess the abundance of IL-1beta and TNFalpha mRNA. In situ hybridization with digoxigenin-labeled cDNA probes was used to localize gene expression. Persistent overexpression of both IL-1beta and TNFalpha were found at 2 and 16 weeks in the lungs of silica-exposed mice compared with air-sham control mice. IL-1beta and TNFalpha expression localized to individual mononuclear cells in the alveolar spaces, groups of cells within the aggregate lesions, and scattered mononuclear cells in BALT and lymphoid nodules. Thus, cells producing IL-1beta and TNFalpha appear to be intimately associated with the evolving lesions of silicosis, and the lymphoid tissue of the lung may be important in driving the pathogenesis of this disease.

Animals↗
PubMed1997

Germ-layer surface tensions and "tissue affinities" in Rana pipiens gastrulae: quantitative measurements.

The morphogenetic properties causing germ-layer spreading and stratification in amphibian gastrulation were called "tissue affinities" by Holtfreter. The differential adhesion hypothesis (DAH) attributes such liquid-like tissue rearrangements to forces generated by intercellular adhesions within and between the migrating cell populations. This theory predicts that, among the primary germ layers, the cohesiveness of deep ectoderm should be the greatest, that of deep mesoderm should be intermediate, and that of deep endoderm should be the least. Also, the cohesiveness of differentiating neural ectoderm should increase after induction, causing it to internalize and segregate from epidermis. The DAH also explains why the cohesiveness of "liquid" tissues, whose cells are free to rearrange, should be measurable as tissue surface tensions. Using a specially designed tissue surface tensiometer, we demonstrate that (i) aggregates of Rana pipiens deep germ layers do possess liquid-like surface tensions, (ii) their surface tension values lie in precisely the sequence necessary to account for germ-layer stratification in vitro and in vivo, and (iii) the surface tension of deep ectoderm just underlain by the archenteron roof is twice that of not-yet-underlain deep ectoderm. These measurements provide direct, quantitative evidence that the "tissue affinities" governing germ-layer flow during early stages of vertebrate morphogenesis are reflected in tissue surface tensions.

Animals↗
PubMed1997

T-lymphocyte activation in the enlarged thoracic lymph nodes of rats with silicosis.

Silicosis is primarily a mononuclear cell inflammatory and fibrotic disease of the pulmonary parenchyma. It is known that lung-associated lymph nodes are also affected. To study the involvement of lymphocytes in silicosis, we examined lymph nodes of rats 12 months after an 8-day silica aerosol exposure. We found that 2 thoracic lymph nodes close to the thymus were enormously enlarged in silicotic rats and contained a 49-fold higher cell number than control lymph nodes. The higher cell number was caused by parallel increases in T- and B-lymphocytes, natural killer (NK) cells, and macrophages without change in the relative proportions when compared with control thoracic lymph nodes. By examining interleukin-2 (IL-2) receptor and intercellular adhesion molecule-1 expression, we detected a significantly higher percentage of activated CD8+ T cells and, to a lower degree, of CD4+ T cells in thoracic lymph nodes of silicotic animals. In contrast, no differences in the activation state were found in T cells obtained from cervical or mesenteric lymph nodes of silicotic and control rats. The occurrence of activated T cells in thoracic lymph nodes of silicotic rats was documented further by selectively enhanced interferon-gamma (IFN-gamma) mRNA expression in the absence of IL-2 and IL-4 mRNA changes. These data show that T-lymphocytes of thoracic lymph nodes have become activated with an enhanced IFN-gamma gene transcription which may be an important cause of macrophage activation during silicosis.

Animals↗
PubMed1996

Mitochondrial genome damage associated with cigarette smoking.

We have investigated the level of mitochondrial DNA (mtDNA) damage and deletions in bronchoalveolar lavage tissues from smokers and nonsmokers using quantitative, extra-long PCR and a "common" mtDNA deletion assay. Smokers had 5.6 times the level of mtDNA damage, 2.6 times the damage at a nuclear locus (beta-globin gene cluster), and almost 7 times the level of a 4.9-kb mtDNA deletion compared to nonsmokers, although the latter increase was not significant. Although both genomes (mitochondrial and nuclear) showed significantly increased levels of DNA damage in smokers (mtDNA P = 0.00072; beta-globin P = 0.0056), the relative differences were greatest in the mtDNA. Damage to the mtDNA may inhibit oxidative phosphorylation and, therefore, potentially cause or contribute to chronic lung disease and cancer. Consequently, the mtDNA may be a sensitive biomarker for environmentally induced genetic damage and mutation.

Adult↗
PubMed1996

Inhibition of LPS-induced tumor necrosis factor-alpha production by colchicine and other microtubule disrupting drugs.

Colchicine has been shown to act as an antiinflammatory agent. In this study, we examined whether colchicine and other microtubule-depolymerizing drugs affected the production of TNF-alpha. When rat peritoneal macrophages were stimulated by LPS, addition of colchicine, vincristine, vinblastine or nocodazole was found to inhibit TNF-alpha release in a concentration-dependent manner. Suppression of TNF-alpha release was not due to interference with secretion as the cytokine did not accumulate intracellularly following colchicine treatment. Colchicine markedly enhanced PGE2 release from LPS-stimulated macrophages. However, addition of the cyclooxygenase inhibitor indomethacin only partially reversed the suppressive effect of colchicine on TNF-alpha production. Colchicine caused a strong reduction of LPS-induced TNF-alpha mRNA accumulation, suggesting that a pretranslational effect may represent the primary mechanism by which colchicine reduced TNF-alpha production. These observations could have clinical relevance in ameliorating undesirable effects due to excessive TNF-alpha production, for example following LPS stimulation of monocytes/macrophages in gram-negative sepsis. Furthermore, these drugs may provide useful tools to study the apparent involvement of the microtubular system in cytokine gene expression and cytokine production.

Animals↗
PubMed1996

Suppression of LPS-induced tumor necrosis factor-alpha gene expression by microtubule disrupting agents.

Microtubule disrupting agents such as colchicine have been shown to reduce TNF-alpha production in macrophages. To examine molecular mechanisms underlying the action of colchicine, TNF-alpha gene expression was studied in the murine macrophage cell line PU5-1.8. An LPS stimulation caused an intense up-regulation of TNF-alpha gene expression which was followed by a high TNF-alpha protein production. Simultaneous addition of colchicine (10 microM) suppressed LPS-induced TNF-alpha mRNA accumulation by one-third and TNF-alpha protein release by two-thirds. This effect was shared by vinblastine and vincristine, chemically different agents that also disrupt microtubule polymerization. For full suppressive activity on TNF-alpha gene expression, colchicine had to be present for 3 h in LPS-stimulated macrophage cultures. With nuclear run-on transcription experiments we could demonstrate that colchicine primarily inhibited de novo gene transcription and did not accelerate degradation of TNF-alpha mRNA in actinomycin D-treated macrophages. Thus, the well-known antiinflammatory action of microtubule depolymerizing agents may be largely due to a reduced TNF-alpha gene expression.

Animals↗
PubMed1996

Reproductive aging: accelerated ovarian follicular development associated with a monotropic follicle-stimulating hormone rise in normal older women.

Women experience a decline in fertility that precedes the menopause by several years. Previous studies have demonstrated a monotropic rise in FSH associated with reproductive aging: however, the mechanism of this rise and its role in the aging process are poorly understood. The purpose of this study was to characterize ovarian follicular development and ovarian hormone secretion in older reproductive age women. Sixteen women, aged 40-45 yr, with regular ovulatory cycles were studied. The control group consisted of 12 ovulatory women, aged 20-25 yr. Serum obtained by daily blood sampling was analyzed for FSH, LH, estradiol (E), progesterone, and inhibin (Monash polyclonal assay). Follicle growth and ovulation were documented by transvaginal ultrasound. Older women had significantly higher levels of FSH throughout the menstrual cycle. E, progesterone, LH, and inhibin levels did not differ between the two age groups when compared relative to the day of the LH surge. Ultrasound revealed normal growth, size, and collapse of a dominant follicle in all subjects. Older women had significantly shorter follicular phase length associated with an early acute rise in follicular phase E, reflecting accelerated development of a dominant follicle. We conclude that older reproductive age women have accelerated development of a dominant follicle in the presence of the monotropic FSH rise. This is manifested as a shortened follicular phase and elevated follicular phase E. The fact that ovarian steroid and inhibin secretion were similar to those in the younger women suggests that elevated FSH in women of advanced reproductive age may represent a primary neuroendocrine change associated with reproductive aging.

Adult↗