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Biomedical subjects

J Kelley

Publications and source records attributed to J Kelley.

At least 73 records · Page 4Linked to original sources
PubMed1991

Construction of playgrounds for chimpanzees in biomedical research.

An outdoor 9,000 sq. ft. playground connected to the indoor-outdoor runs of the breeding facility at Southwest Foundation for Biomedical Research was constructed to simulate a near natural environment for chimpanzees in biomedical research. It is divided into three 75 X 40 ft. compounds to allow several groups of animals to utilize the area simultaneously. Environmental enrichment devices have been added to improve physical and psychological well-being.

Animals↗
PubMed1990

Incisor microwear and diet in three species of Colobus.

Examination of incisor microwear in three species of Colobus revealed that the predominantly folivorous C. badius more closely resembles C. satanas, a seed predator/folivore, than C. guereza, another predominantly folivorous species. This demonstrates that species of the same broad dietary category can have very different patterns of incisor microwear, indicative of differences in food procurement behavior and/or the physical properties of dietary items for some portion of the diet. Conversely, species of different categories can have microwear patterns that, superficially at least, are quite similar. The dissimilarity in incisor microwear between C. badius and C. guereza is mirrored to a certain extent in molar microwear, although the differences are not nearly so great on the molars. The differences between C. badius and C. guereza may involve different food items in the major, folivorous portions of their diets, or they may relate to differences in the very minor fruit and bark components. The similar microwear patterns of C. badius and C. satanas demonstrate that incisor microwear by itself is unreliable for assigning fossil species to broad dietary categories. Incisor microwear can be used to infer finer dietary distinctions in fossil species for which dietary category has been determined by other means.

Animals↗
PubMed1990

Cytokines of the lung.

Communication between cells determines the steady-state composition of the lung in health and becomes a critical determinant of outcome in pathologic processes resulting in anatomic remodeling. This review presents the evolving concepts of the biology of cytokines (also known as peptide growth factors or biological response modifiers) in maintaining normal tissue growth and homeostasis. How these extracellular signaling proteins are involved in such pathologic disorders as spontaneous pulmonary fibrosis, sarcoidosis, pneumoconiosis, and the evolution and recovery from acute lung injury is also discussed. During the past decade the cytokines have come to the fore as important multifunctional mediators of cell behavior and cell-cell communication. A wide range of cellular responses are influenced or triggered when cytokines interact with cells. These include mitosis, chemotaxis, angiogenesis, cytoskeleton arrangement, immunomodulation, and extracellular matrix production. Cytokines influence cell behavior by binding to specific high affinity surface receptors on target cells. These receptors are linked in turn at the cell membrane to a complex array of intracellular signaling pathways. Individual cytokines may inhibit as well as promote cellular functions such as mitosis and thereby play a critical role in homeostasis of normal tissue elements. Hence, cytokines are intimately involved in normal tissue homeostasis as well as in processes eventuating in growth and remodeling. All cells produce and secrete cytokines at some time during their life. Each cytokine is capable of modulating more than one cellular function. Although produced by a variety of cell types, the triggers that induce a specific cytokine to be produced differ between cells. Many of the cytokines share regions of homologous nucleic acid sequences, suggesting that they are members of larger gene families. Given that tissues and cells are exposed to complex cytokine mixtures rather than to individual cytokines, recent attention has turned to understanding how cytokines interact. The combined effects of cytokine mixtures have proved to be both complex and unpredictable based on knowledge of the separate actions of the individual cytokines involved. In studies of the role of cytokines in lung disease, early research attention has focused on those cytokines released by alveolar macrophages (the so-called macrophage-derived growth factors). However, structural cells as well as immune effector cells of the lung are capable of cytokine production and release. The cytokines receiving the most attention to date in relation to pulmonary diseases include platelet-derived growth factor (PDGF), interleukin-1 (IL-1), transforming growth factor-beta (TGF-beta), tumor necrosis factor-alpha (TNF-alpha), insulinlike growth factor I (IGF-I), and, most recently, interleukin-6 (IL-6).(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Factors↗
PubMed1990

Use of selected nursing diagnoses: a transcultural comparison between Mexican and American nurses.

While use of nursing diagnoses has increased both in the United States and abroad, there have been few reports on the use and applicability of the diagnostic categories across culturally distinct populations. The authors report a preliminary study which compared the use of selected diagnostic categories in an American group and a Mexican group of nurses. Data indicate that nurses did not demonstrate consistency with one another in use of diagnoses either within each group or between groups. The authors caution that further study and documentation of how diagnoses are understood and used by practitioners is needed before widespread international or transcultural usage in encouraged.

Cross-Cultural Comparison↗
PubMed1990

Caprine beta-mannosidosis. Abnormal thyroid structure and function in a lysosomal storage disease.

Deficient activity of the lysosomal enzyme beta-mannosidase leads to widespread tissue accumulation of oligosaccharides in caprine beta-mannosidosis, an autosomal recessive neurovisceral storage disease. Severe thyroid morphologic abnormalities found in a previous light microscopic survey of tissues from neonatal affected goats suggested the possibility of impairment of function. Since considerable evidence indicates that thyroid hormone plays an important role in regulation of myelination, thyroid hormone deficiency, if present during central nervous system development, could be a factor in the hypomyelination seen in affected animals. Thus, this study was designed to characterize thyroid structure and function in beta-mannosidosis. To investigate developmental aspects of structural abnormalities, thyroids from six pairs of affected and control animals ranging in age from 96/150 days gestation to 3 days postnatal were analyzed by light and electron microscopy. Major findings in thyroids from affected animals, as early as 96/150 days gestation, included follicle irregularities and pronounced presence of lysosomal storage vacuoles in all cell types, particularly in follicular cells. The degree of cytoplasmic vacuolation increased with advancing age. To assess thyroid function, thyroid hormone concentrations were determined in six age-matched, neonatal pairs of affected and control goats. Significantly decreased thyroid hormone concentrations were present in affected animals. It is hypothesized that thyroid hormone deficiency plays a role in the pathogenesis of hypomyelination in affected animals. This study comprises, to our knowledge, both the most complete description of developmental abnormalities and the first report of abnormal function in an endocrine organ in a lysosomal storage disease. Further, this report suggests that systemic perturbations induced by a genetically determined deficiency of a lysosomal hydrolase could be a factor in the pathogenesis of central nervous system lesions.

Aging↗
PubMed1989

Localization of collagen in the rat lung: biochemical quantitation of types I and III collagen in small airways, vessels, and parenchyma.

The marked insolubility of pulmonary collagen has limited its accurate biochemical quantitation in small samples of lung and other tissues. We have recently developed a microassay based on radioisotope dilution techniques that we have used for the accurate determination of types I and III collagen in extremely small tissue samples. By applying this method to carefully dissected small airways and vessels and samples of parenchymal tissue of rat lungs, we have localized and quantitated biochemically the type I and III structural collagens of the lung. Large pulmonary arteries are the units richest in these interstitial collagen types on the basis of dried tissue weight (50 micrograms/100 micrograms dried tissue). Amounts of both types I and III collagen are considerably lower in the alveolar domain than in vessels and airways of the rat lung. The proportion of tissue composed of these collagen types decreases centripetally in rat pulmonary arteries, but increases in the bronchial tree. The relative proportions of type I and type III remain constant in all the structures tested. The higher total amount of collagen in the nonalveolar domain has implications for biochemical studies based on whole lung samples.

Animals↗
PubMed1989

Phlorizin-induced glycosuria does not prevent gentamicin nephrotoxicity in rats.

Because rats with streptozotocin-induced diabetes mellitus (DM) have a high solute diuresis (glycosuria of 10 to 12 g/day), we have suggested that this may in part be responsible for their resistance to gentamicin-induced acute renal failure (ARF). The protection from gentamicin nephrotoxicity was studied in non-diabetic rats with chronic solute diuresis induced by blockage of tubular glucose reabsorption with phlorizin (P). DM rats with mild glycosuria (similar in degree to that of the P treated animals) were also studied. Unanesthetized adult female, Sprague-Dawley rats were divided in four groups and studied for 15 days. Group 1 (P alone) received P, 360 mg/day, for 15 days; Group II (P + gentamicin); Group III (gentamicin alone) and Group IV (mild DM + gentamicin). Nephrotoxic doses (40 mg/kg body wt/day) of gentamicin were injected during the last nine days of study to the animals of groups II to IV. In Group I, P induced a moderate and stable glycosuria (3.9 +/- 0.1 g/day, SE), and no functional or morphologic evidence of renal dysfunction (baseline CCr 2.1 +/- 0.1 ml/min, undetectable lysozymuria) or damage (tubular necrosis score [maximum 4], zero). In Group II, P did not prevent gentamicin-ARF (maximal decrease in CCr at day 9.89%, P less than 0.001; peak lysozymuria, 1863 +/- 321 micrograms/day; and tubular necrosis score, 3.9 +/- 0.1). These values were not different from those of Group III: maximal decrease in CCr 73% (P less than 0.001); lysozymuria, 2147 +/- 701 micrograms/day; tubular necrosis score, 3.8 +/- 0.1.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1989

Increased expression of PDGF-B (c-sis) mRNA in rat lung precedes DNA synthesis and tissue repair during chronic hyperoxia.

Several aspects of tissue response to injury, including cell proliferation, cell migration, and deposition of extracellular matrix, have been attributed to platelet-derived growth factor (PDGF)-like cytokines. Because these responses play key roles in lung injury, PDGF-B (c-sis) gene expression was measured by Northern blot analysis of lung total RNA prepared after oxidant injury was induced by chronic exposure of rats to 85% oxygen for zero, 1, 3, and 7 days. Constitutive but low levels of PDGF-B mRNA (4.0 kb) were observed in the lungs of control animals exposed to 21% oxygen. Steady-state levels of PDGF-B mRNA in lung were elevated 2.5-fold by day 3 of hyperoxia and remained so up to at least day 7. The early increase in PDGF-B mRNA expression after 3 days of hyperoxic exposure preceded several other aspects of the reparative response. DNA synthesis measured by in vivo incorporation of [3H]thymidine into lung DNA was unchanged at day 3 but markedly elevated by day 7. A similar increase in extractable lung RNA implies a quantitative or qualitative change in extractable RNA at this later phase of tissue injury. Subtle changes in actin mRNA expression were also noted late in the course of lung injury. The content of cytoplasmic (beta,gamma) actin mRNA (2.1 kb) in lung was doubled after 7 days of hyperoxia (P less than 0.05). In addition, increased expression of an actin cDNA-hybridizing mRNA, which co-migrates with muscle-specific alpha-actin mRNA (1.7 kb), was detected on day 7, suggesting hyperplasia of smooth muscle and myofibroblasts. These data show that PDGF-B transcripts are constitutively expressed in rat lung tissue. The expression of PDGF-B mRNA increases early in the course of hyperoxic lung injury and precedes an increase in DNA synthesis and other responses that reflect tissue remodeling. These results suggest that the production of PDGF-like cytokines by cells within the lung itself initiates or modulates various aspects of lung injury and repair.

Actins↗
PubMed1989

Early markers of lung injury.

The goal of this study was to develop an early marker of lung injury that might change in response to exposure to a mobile source emission. Nitrogen dioxide (NO2)2 was chosen as an example of an atmospheric pollutant that is related to automobile emissions. Since reorganization of the connective tissue matrix of the lung occurs in response to injury, markers of connective tissue metabolism were selected as targets. Hydroxylysine became the marker of choice. It is an amino acid that is virtually exclusive to collagen, although it does occur in minimal amounts in other proteins. Furthermore, it is excreted in the urine, which makes it readily available for analysis using noninvasive techniques. Other markers evaluated as part of the study included angiotensin-converting enzyme as a marker of lung injury, desmosine as a marker of elastin degradation, and hydroxyproline as another marker of collagen metabolism. Male Fischer-344 rats were exposed in whole-body chambers to controlled concentrations of NO2 for various doses and periods of time. The concentrations of NO2 ranged from 0.5 to 30 parts per million (ppm); the rats were exposed for six hours per day for periods of two days to four weeks. Urine and bronchoalveolar lavage samples were collected and analyzed for the appropriate marker. In addition, pulmonary function studies and histologic examinations of the lungs were completed at selected time points. Urinary hydroxylysine concentration increased as a function of NO2 concentration during six-hour-per-day exposures for two days. This short-term exposure required relatively high doses to achieve significant changes in the hydroxylysine output. During one-week exposures to either 25 or 30 ppm NO2, there was an increase in urinary hydroxylysine associated with changes in lavage concentrations of angiotensin-converting enzyme and hydroxylysine. The lungs of these animals demonstrated histologic changes typical of oxidant injury. Four-week exposure protocols using 0.5 and 1 ppm NO2 were most interesting in terms of the sensitivity of the marker. There was minimal damage revealed by the histology and function studies, yet there were significant increases in the excretion of hydroxylysine. It appears that hydroxylysine can be indicative of exposure when other parameters are normal. It will require long-term follow-up of exposed rats to determine whether or not the change in marker concentration is predictive of damage. Hydroxylysine may be an excellent marker of exposure to oxidants in the human population. Controlled studies to establish base-line values are needed, followed by carefully controlled studies in individuals with connective tissue abnormalities of the lung.

Animals↗
PubMed1988

Lavage angiotensin-converting enzyme as a marker of lung injury.

The source of angiotensin-converting enzyme (ACE) in lavage fluid remains controversial. I reassessed the levels of ACE in lavage fluid in contrasting models of lung injury in rats. In all 3 models examined, there was at least a 3-fold elevation in both ACE activity and total protein levels. However, determination of enzyme activity relative to total protein content (enzyme specific activity) revealed contrasting patterns. High dose intratracheal bleomycin instillation (500 micrograms) induced an increase in ACE activity relative to total protein. When a lower dose of bleomycin (50 micrograms) or when a 30-h exposure to 100% oxygen were used, both ACE and protein increased but enzyme specific activity did not change. In contrast, exposure to 100% oxygen for 48 h or to alpha-naphthylthiourea, an agent that rapidly induces protein edema without cell injury, caused a decrease in enzyme specific activity. The enzyme found in lavage fluid in these models is identical to the lung tissue enzyme with respect to cofactor requirements, inhibition by captopril, and has an apparent molecular weight of 175 kDa by SDS-polyacrylamide gel electrophoresis. These studies clearly refute the null hypothesis that lavage ACE levels in the injured lung merely reflect altered bulk protein transmigration.

Animals↗
PubMed1987

Effects of pretreatment with benzo[a]pyrene on the stereochemical selectivity of metabolic activation of benzo[a]pyrene to DNA-binding metabolites in hamster embryo cell cultures.

The proportions of individual benzo[a]pyrene (BaP)-DNA adducts present in rodent embryo cell cultures change with the length of time of exposure to BaP; the major alteration is an increase in the proportion of (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydroBaP (BaPDE)-deoxyguanosine (dG) adduct (Sebti et al., Cancer Res., 45 (1984) 1594-1600). To determine if this change in the BaP-DNA adducts could result from the induction of enzymes involved in oxidation of BaP, hamster embryo cell cultures were exposed to acetone or BaP for 24 h and then the medium was replaced with fresh medium containing [3H]BaP. After 5 h the BaP-pretreated cells had a 30% higher level of binding of BaP to DNA and formed a greater proportion of (+)-anti-BaPE-dG adduct than the acetone-pretreated control group. Cells pretreated for 24 h with BaP and then exposed to [3H]BaP and Actinomycin D for 5 h had a lower level of binding of BaP to DNA and a lower amount of (+)-anti-BaPDE-deoxyguanosine adduct than cells pretreated with acetone and exposed to [3H]BaP for 5 h. In contrast, pretreatment for 24 h with BaP plus Actinomycin D followed by a 5-h exposure to [3H]BaP resulted in a decrease in overall binding of BaP to DNA but had no effect on the amount of (+)-anti-BaPDE-deoxyguanosine adduct. Actinomycin D treatment had no significant effect on either the total amount of BaP metabolized, the formation of primary and water-soluble BaP metabolites, or cell viability, but reduced [3H]uridine incorporation into RNA by more than 65% at all times. These results suggest that induction of specific isozymes of cytochrome P-450 may be involved in the time-dependent increase in the proportion of (+)-anti-BaPDE-DNA adducts in BaP-treated cells. The state of induction of specific isozymes of cytochrome P-450 and the ability of the BaP dose applied to induce them may be major factors in determining the proportion of BaP metabolized to (+)-anti-BaPDE, the most carcinogenic stereoisomer of BaPDE.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1987

Partition of lactic streptococcal bacteriophage during the ultrafiltration concentration of milk and whey.

Milk and whey inoculated with lactic streptococcal bacteriophages 316, or 322, or both were concentrated by UF using a DDS Mini-Lab 20. The plate and frame unit was fitted with Type GR61PP polysulfone membrane with a 20,000 molecular weight cutoff. The unit was operated at an inlet pressure of .40 MPa and an outlet pressure of .23 MPa with an initial flux of 2.0 to 3.0 L/h. Samples of retentate, permeate, and membrane were analyzed for the presence of bacteriophages. Under the conditions established in this study, phage particles did not pass through the membrane but instead became trapped in the polarization concentration layer or in the membrane. Phages were recovered from the membrane by extraction in sterile buffered water with the Stomacher. The UF concentration of milk containing the host species of Streptococcus cremoris resulted in phage propagation and lysis of the host but did not result in the passage of phages through the membrane. The UF processing of milk or whey should produce a phage-free permeate.

Animals↗
PubMed1987

Lend me your ear!

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Hospital Administration↗
PubMed1986

Intra-alveolar release of a competence-type growth factor after lung injury.

Growth factors released by platelets, macrophages, and endothelial and smooth muscle cells have been recognized and characterized using in vitro tests of isolated cell populations. However, their production, secretion, and effects on target cells in situ after tissue injury remains largely presumptive. Alveolar macrophages cultured during acute and chronic lung injury release increased amounts of macrophage-derived growth factor (MDGF). In the present study, we sampled the alveolar lining fluid by lavage for the presence of macromolecular competence factor activity. We report that alveolar lavage fluid obtained following acute lung injury induced by bleomycin in the rat contains large amounts of soluble growth factor activity not found in lung lavage fluid from normal animals. We compared the properties of the growth factor found in fresh lavage fluid to MDGF and platelet-derived growth factor (PDGF). The amount of growth factor in lavage fluid paralleled the ability of cultured alveolar macrophages to release MDGF. Like PDGF and MDGF, lavage fluid growth factor served as a competence factor promoting the reentry of quiescent fibroblasts into the cell cycle rather than as a progression factor. Chromatography on DEAE-Sephacel yielded a single peak of growth factor activity eluting at 0.3 M NaCl. On the basis of these and other physical and biologic properties, we conclude that growth factor activity found in high levels in the alveolar space following acute lung injury resembles MDGF. Growth factor present in the alveolar space may provide the major local stimulus to lung structural cell replication after acute lung injury.

Animals↗
PubMed1986

Protein synthesis in the growing rat lung.

Developmental control of protein synthesis in the postnatal growth of the lung has not been systematically studied. In male Fischer 344 rats, lung growth continues linearly as a function of body weight (from 75 to 450 g body weight). To study total protein synthesis in lungs of growing rats, we used the technique of constant intravenous infusion of tritiated leucine, an essential amino acid. Lungs of sacrificed animals were used to determine the leucine incorporation rate into newly synthesized protein. The specific radioactivity of the leucine associated with tRNA extracted from the same lungs served as an absolute index of the precursor leucine pool used for lung protein synthesis. On the basis of these measurements, we were able to calculate the fractional synthesis rate (the proportion of total protein destroyed and replaced each day) of pulmonary proteins for each rat. Under the conditions of isotope infusion, leucyl-tRNA very rapidly equilibrates with free leucine of the plasma and of the extracellular space of the lung. Infusions lasting 30 minutes or less yielded linear rates of protein synthesis without evidence of contamination of lung proteins by newly labeled intravascular albumin. The fractional synthesis rate is considerably higher in juvenile animals (55% per day) than in adult rats (20% per day). After approximately 12 weeks of age, the fractional synthesis rate remains extremely constant in spite of continued slow growth of the lung. It is apparent from these data that in both young and adult rats the bulk of total protein synthesis is devoted to rapidly turning over proteins and that less than 4 percent of newly made protein is committed to tissue growth.

Animals↗