Search PubMed⌕ Search

Biomedical subjects

G S Davis

Publications and source records attributed to G S Davis.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1996

Eggshell conductance and other functional qualities of ostrich eggs.

Eggshell conductance was measured and eggshell conductance constants were calculated for eggs from ostriches. In addition, egg water, yolk, albumen, shell, and total solids were measured in an effort to determine the maternal investment of ostrich eggs. The results of the study suggest that the optimal incubator humidity for ostrich eggs is less than 25% to allow a 15% loss of initial egg mass during the 45-d incubation period. This low humidity does not preclude increasing humidity during the actual hatching process. In addition, incubation temperatures need to be adjusted to allow a longer development time for the embryo to attain an adequate level of maturity to survive the plateau stage in oxygen consumption or to prevent the use of limited energy of the yolk to survive the anoxia of tucking and internal pipping. The optimal incubation temperature of ostrich eggs appears to be between 36.1 and 36.9 C.

Animals↗
PubMed1995

Egg characteristics, carbohydrate metabolism, and thyroid hormones in late chick embryos from different genetic lines.

Functional eggshell qualities, thyroid hormones, and carbohydrate metabolism of chick embryos at the end of incubation were compared between a modern (Arbor Acres line) and a randombred control population (Athens-Canadian Randombred). Embryos from the Arbor Acres genetic line developed in larger eggs with more albumen and less yolk than Athens Canadian Randombred lines. Percentage shell and functional eggshell properties measured as eggshell conductance constants did not differ between genetic lines. On a relative basis, hearts were generally smaller and livers heavier in Arbor Acres than in Athens-Canadian Randombred birds. Heart and liver glycogen concentrations were greater in Athens-Canadian Randombred than in Arbor Acres embryos. However, blood glucose was greater in Randombred than in Arbor Acres embryos only at internal pipping, a time of hypoxia and hypercapnia. Blood plasma concentrations of thyroxine did not differ significantly between the modern and Randombred embryos at any stage examined. Modern broiler chick embryos possessed greater concentrations of triiodothyronine as well as greater triiodothyronine to thyroxine ratios than Randombred embryos at external pipping and hatching. It can be inferred from the data that chick embryos differ in their use of carbohydrate during late development between modern and Randombred genetic lines.

Animals↗
PubMed1995

Effect of exogenous adrenocorticotropic hormone administration on plasma corticosterone concentrations in American black ducks (Anas rubripes).

A protocol for the adrenocorticotropic (ACTH) stimulation test in American black ducks (Anas rubripes) was established with synthetic ACTH, cosyntropin (Cortrosyn); ACTH stimulation testing was conducted on 31 adult ducks (14 males, 17 females) in September 1993. Plasma corticosterone concentrations were measured on heparinized blood samples collected 30 min, and 1, 2, and 4 hr post-injection. In comparison with saline controls, cosyntropin (0.25 mg/duck) produced a two- to three-fold increase in corticosterone 30 min after administration. Maximal concentrations ranged from 132 to 312 ng/ml and occurred between 1 and 2 hr post-injection. Corticosterone concentrations declined to basal, pre-injection values after 4 hr. Endogenous ACTH release in response to handling stress was evident in control ducks after saline injection but did not interfere with interpretation of the stimulation test. Recommendations for the ACTH stimulation test in black ducks include a 30 min acclimatization period for recently captured or relocated ducks and determination of plasma corticosterone concentration 1 to 2 hr following intramuscular injection with 0.25 mg cosyntropin.

Adrenal Cortex Function Tests↗
PubMed1992

Serum and bronchoalveolar lavage of N-terminal type III procollagen peptides in idiopathic pulmonary fibrosis.

Collagen deposition is a prime determinant of clinical course in idiopathic pulmonary fibrosis (IPF). Identification of a marker of connective tissue metabolism would significantly enhance the ability to stage the disease and monitor the course of these patients. Prior studies of IPF have indicated that N-terminal Type III procollagen peptide (N-PIIIP) levels in blood and bronchoalveolar lavage BAL fluid are elevated. We hypothesized that elevated levels of procollagen peptides are a marker of enhanced collagen deposition, which is associated with interstitial fibrosis characterizing active disease. The purpose of the present study was to explore the relationship between N-PIIIP recovery and physiologic parameters of lung function. N-PIIIP levels in sera and bronchoalveolar lavage (BAL) from 24 patients with IPF and 29 volunteers were measured by radioimmunoassay. The extent of disease in IPF was assessed by clinical history, physical examination, chest radiograph, pulmonary physiology evaluation, and confirmatory open-lung biopsy. The severity of disease was graded using a previously described clinical, radiologic, and physiologic (CRP) scoring system. N-PIIIP normalized to albumin was higher in BAL than in serum for both volunteers (1.6-fold; p less than 0.05) and IPF patients (24-fold; p less than 0.05), consistent with local pulmonary production. BAL N-PIIIP was significantly elevated in IPF patients, whether expressed as concentration (healthy volunteer 0.11 +/- 0.06 ng/ml; IPF, 5.0 +/- 14.4; mean +/- SD; p less than 0.05) or normalized to albumin (healthy volunteer, 2.8 +/- 1.2; IPF, 73 +/- 106; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Enhanced release of prostaglandin E2 from macrophages of rats with silicosis.

The pathogenesis of silicosis results, in part, from interactions between silica particles and alveolar macrophages (AM) with release of cytokines and other mediators. Different arachidonic acid metabolites have been shown to promote or to suppress inflammation and fibrosis. We designed experiments to study the production of cyclooxygenase metabolites and tumor necrosis factor-alpha (TNF-alpha) from macrophages during active silicosis. Macrophages were harvested from rats 5 to 7 mo after an 8-day silica aerosol exposure. Upon in vitro culture of AM, the spontaneous release of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and prostaglandin D2 (PGD2) of silica-exposed animals was higher than that of sham-exposed animals. Moreover, AM from silicotic rats displayed an increased sensitivity to low concentrations of lipopolysaccharide (LPS, 10 ng/ml) and released copious amounts of PGE2 and TXB2. When compared with similarly enhanced release of TNF-alpha from AM of silica-exposed rats, PGE2 production occurred later and started to increase when TNF-alpha production declined. Addition of the cyclooxygenase blocker indomethacin augmented TNF-alpha production, whereas the addition of PGE2 counteracted TNF-alpha release. Also peritoneal macrophages, which did not have direct contact with silica particles, released enhanced levels of PGE2 in response to low LPS doses. We conclude that AM and other macrophages from silica-exposed rats are preactivated and display an enhanced prostanoid production that could serve anti-inflammatory or immunomodulating roles in silicosis.

Animals↗
PubMed1992

Reduced release of leukotrienes B4 and C4 from alveolar macrophages of rats with silicosis.

Silicosis leads to altered release of fibrogenic and immunomodulating mediators from alveolar macrophages (AM). Since 5-lipoxygenase metabolites have been shown to possess proinflammatory effects and to promote the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) from mononuclear phagocytes, we determined leukotriene secretion from silica-exposed AM. Rats were exposed to an aerosol of silica particles for 8 days and AM were harvested by bronchoalveolar lavage 5 to 7 mo after exposure. AM from both air-sham control and silica-exposed rats displayed minimal spontaneous leukotriene release upon in vitro culture. Stimulation with opsonized zymosan particles induced leukotriene B4 (LTB4) and leukotriene C4 (LTC4) secretion, which was much greater in control AM than in AM from silica-dusted rats. The reverse was found for zymosan-induced TNF-alpha production, which was higher in AM from silica-exposed than from control rats. To study the interrelation between leukotriene and TNF-alpha release, we incubated zymosan-stimulated AM with the 5-lipoxygenase inhibitor VZ 65. VZ 65 suppressed zymosan-induced TNF-alpha release from AM in a dose-dependent manner, and TNF-alpha production could be restored almost completely by addition of LTB4. These experiments demonstrate that silica exposure resulted in a decreased LTB4 and LTC4 production from AM, which may represent a regulatory mechanism to counterbalance enhanced TNF-alpha production during silicosis.

Animals↗
PubMed1991

Effects of work exposure, retirement, and smoking on bronchoalveolar lavage measurements of lung dust in Vermont granite workers.

Estimation of the exposure to respirable dust in the workplace is an important aspect of industrial hygiene. We performed bronchoalveolar lavage (BAL) on 42 healthy nonindustrial control subjects and 44 workers in the Barre, Vermont granite industry to determine whether BAL materials reflected occupational exposure. The granite workers held jobs with a range of dust exposure intensities and had employment histories from 1 to 43 yr; 12 workers were retired. None of the workers had radiologic evidence of silicosis. The granite dust content of BAL materials was measured by enumerating the percentage of cells positive for particulates by polarized light microscopy, by analysis for silicon by scanning electron microscopy with energy-dispersive X-ray spectrometry, and by chemical analysis. Minerals were present in greater quantity in the BAL cells from granite workers than from nonindustrial control subjects. Polarized light microscopy was comparable in sensitivity, specificity, and overall accuracy to electron microscopy; chemical analysis was less accurate than either microscopic technique. Tobacco smoking did not interfere with the detection of the occupationally related minerals or influence the quantity of dust present. The mineral in BAL cells was partially related to the intensity of exposure within the granite industry and to the duration of employment, but there was great individual variation among subjects. Retirement led to a decrease in BAL mineral content, but substantial dust remained for many years.

Bronchoalveolar Lavage Fluid↗
PubMed1991

Systemic macrophage stimulation in rats with silicosis: enhanced release of tumor necrosis factor-alpha from alveolar and peritoneal macrophages.

In silicosis, alveolar macrophages (AM) are thought to induce chronic inflammation and fibrosis by release of cytokines. Rats were exposed to aerosols of alpha-quartz and examined 4 to 9 mo later for persistence of silica particles and release of tumor necrosis factor-alpha (TNF-alpha) from macrophages. Silica particles were detected in AM, lung parenchyma, and thoracic lymphoid organs, whereas extrathoracic lymphoid tissues and organs were free of the mineral. When AM were tested functionally, no spontaneous release of TNF-alpha was observed. However, upon in vitro stimulation of AM from silicotic rats with a low concentration of lipopolysaccharide (10 ng/ml), abundant TNF-alpha production was found that was higher and occurred more rapidly than with AM from sham-exposed animals. Peritoneal macrophages, which did not have contact with silica particles, displayed a similarly enhanced TNF-alpha release in response to low doses of lipopolysaccharide. These data demonstrate a state of systemic preactivation ("priming") of macrophages that supports the notion that silicosis is associated with a general immunostimulation.

Animals↗