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Biomedical subjects

J Kelley

Publications and source records attributed to J Kelley.

At least 55 records · Page 3Linked to original sources
PubMed1993

Auto-induction of transforming growth factor-beta in human lung fibroblasts.

The type beta transforming growth factors (TGF-beta s) are a family of potent cytokines with diverse effects on proliferation, differentiation, turnover of extracellular matrix components, oncogene expression, and other aspects of cellular phenotype. Unlike lung fibroblasts of certain species, unstimulated human lung fibroblast lines produce little or no TGF-beta in culture. However, TGF-beta has been reported to autoregulate its own production in certain human tumor cells and in rodent cell lines. To test whether this phenomenon is operative in fibroblasts from normal human lung tissue, confluent cultures of IMR90 normal fetal lung fibroblasts were exposed to TGF-beta. Cultures were exposed briefly to purified TGF-beta 1 under serum-free conditions and secretion of newly synthesized TGF-beta over the ensuing 72 h was determined by immunoblotting and bioassays made specific with the use of neutralizing antibodies. Steady-state levels of mRNA for TGF-beta 1 were detected by Northern and slot blot hybridization analysis of total cellular RNA. The 2.5 kb TGF-beta 1 mRNA species rose within 1.5 h of exposure of IMR90 cells to TGF-beta 1 and reached maximal levels after 16 h. Increased levels of TGF-beta were detected in conditioned medium 9 h after the start of the exposure. Thereafter, TGF-beta continued to accumulate at an elevated rate (90 +/- 7 versus < or = 15 pg/10(6) cells/h in uninduced cells) for up to 72 h. As little as 1 ng/ml TGF-beta 1 auto-induced TGF-beta secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Variable expression of platelet-derived growth factor family proteins in acute lung injury.

During acute lung injury, there is an outpouring of growth factors into the alveolar space that drive local repair and fibrosis. During the remodeling that follows the instillation of bleomycin via the trachea into the adult rat, at least two platelet-derived growth factor (PDGF)-like peptides are released sequentially into lung lining fluid. Groups of four to five animals were killed at 3, 6, 15, and 26 days after exposure to bleomycin and lungs lavaged with isotonic saline. PDGF-like peptides in epithelial lining fluid (ELF) were partially purified by cation exchange chromatography and concentrated. Isolated peptides were analyzed by immunoblotting to determine their molecular weight and immunologic identity. Western blots were probed with polyclonal antibodies to PDGF-BB and PDGF-AA. PDGF-like peptides of two distinct size classes (38-40 kD and 29 kD) were present in alveolar fluid from all rats with lung injury induced by bleomycin. No PDGF-like peptides were found in comparably prepared ELF from control animals. The 38-40 kD peptide was detected only with anti-PDGF-BB antibody; the 29 kD peptide was detected only with anti-PDGF-AA antibody. The presence of these two peptides varied independently with time after exposure to bleomycin. The 38-40 kD peptide was at peak levels at 3 to 6 days. In contrast, the 29 kD peptide was present at all times following injury but with far less variation over time. In parallel with these immunoassays for PDGF-like molecules, there was abundant growth-promoting activity for fibroblasts present in concentrated ELF during the course of injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Moral reasoning and political conflict: the abortion controversy.

We argue that the abortion controversy has one major source--religion--and two less important ones--attitudes towards sexual permissiveness and women's employment. Traditional Christianity promotes opposition to abortion using three distinct modes of moral reasoning: through deductive moral reasoning, by the Christian world view's implication that abortion violates the sanctity of life and is a rebellion against God's design; through authoritative moral reasoning by appeal to Catholic dogma; and through consequentialist moral reasoning, as a means of control over sexuality and as a means of confining women's activities to the home. Even aside from Christian belief, adherence to traditional morality promotes opposition to abortion on these consequentialist grounds. We posit a model in which religious belief, anti-feminism, sexual permissiveness, and attitudes towards abortion are distinct concepts (a four-factor model) rather than all simply aspects of a single conservatism factor. We develop reliable, multiple item attitude scales; show that our four-factor model fits the data much better than the one-factor alternative; and test our hypotheses on new data from a large, representative national sample of Australia (N = 4540). Using maximum likelihood structural equation methods, we find that deductive reasoning from Christian belief is the most important source of opposition to abortion, with strong effects both direct and indirect. Exposure to the authority of the Catholic hierarchy is a real but weaker source of opposition. Consequentialist reasoning from traditional moral views on sex--partly buttressed by religion, partly independent of it--is also influential. But views on women's employment matter only a little, contrary to received wisdom.

Abortion, Legal↗
PubMed1993

Improving the black family's odds for health: a survey of health status and risk factors.

This paper reflects on the factors which affect the excess morbidity and mortality that Black families suffer. Statistical surveys reveal the conditions which generate major stresses, increase health risk factors, and perpetuate inadequate health services. Implications for research and imperatives for health professionals and caregivers which urge intervention strategies and encourage strategically designed health promotion and disease prevention services are included herein.

Adolescent↗
PubMed1992

Spontaneous production of PDGF A-chain homodimer by rat lung fibroblasts in vitro.

Platelet-derived growth factor (PDGF) is considered a decisive mediator of fibroblast growth and phenotype within the lung. The cellular sources of PDGF within the lung remain undefined. The ability of lung fibroblasts themselves to produce PDGF in vitro was therefore investigated. Northern and Western blot analyses revealed the expression of PDGF-A mRNA and secretion of A-chain containing proteins by fibroblasts derived from adult and fetal rat lung. PDGF-A gene or protein expression were below the limits of detection in two human lung fibroblast lines examined in a similar manner. PDGF-B transcripts or proteins were not detected in any lung fibroblast line examined. Conditioned medium (CM) was collected from these same lung fibroblast lines and tested for its ability to promote cell growth using human fetal lung fibroblasts as targets. Both adult and fetal rat lung fibroblasts were found to produce a potent and efficacious stimulus for cell growth. Growth-promoting activity in rat fibroblast-derived CM functioned as a "competence" factor and was partially inhibited by anti-PDGF antibody. Thus rat lung fibroblasts in vitro produce potent growth factors of which at least one appears to be PDGF-AA. Differences in the expression of PDGF-AA between rat and human lung fibroblasts exist. Growth factor-producing fibroblasts may play a role in lung repair and remodeling through production PDGF-AA in vivo.

Animals↗
PubMed1992

Bleomycin regulation of transforming growth factor-beta mRNA in rat lung fibroblasts.

Pulmonary fibrosis is a well-known toxic response to bleomycin treatment. Here we demonstrate the direct effects of bleomycin on lung fibroblasts that resulted in a marked increase of collagen synthesis as compared with total noncollagen protein synthesis. Bleomycin treatment of rat lung fibroblast cultures resulted in an increase of total cellular transforming growth factor-beta (TGF-beta) mRNA and increased secretion of TGF-beta protein into the conditioned media. beta 2-Microglobulin was measured as an mRNA that did not increase with bleomycin treatment. The bleomycin-induced increase of TGF-beta mRNA was decreased by cells cultured in the presence of either cycloheximide, an inhibitor of protein synthesis, or 2-mercapto-1-(beta-4-pyridethyl) benzimidazole, an inhibitor of RNA synthesis. To assess the mechanism underlying increased steady-state mRNA levels, the nuclear fraction was isolated from bleomycin-treated cells and the TGF-beta transcripts were determined. Transcription of TGF-beta mRNA was increased 12 h after bleomycin treatment, whereas the transcription of type I procollagen, type III procollagen, and beta-actin mRNAs were increased after 48 h of bleomycin treatment. beta 2-Microglobulin mRNA synthesis was not increased within this time frame. These results suggest bleomycin regulation of TGF-beta at both the mRNA and protein levels. Rats lung fibroblasts were separated by cell sorting into two subpopulations. One population of fibroblasts demonstrated increased procollagen type I mRNAs, whereas fibroblasts in the other population had increased procollagen type III mRNA. Following bleomycin treatment, TGF-beta mRNA was shown to be located more prominently in those fibroblasts that contain primarily collagen type I mRNAs.

Animals↗
PubMed1992

The ethics of caring: a basis for holistic care.

Interest in the concept of caring and the ethics of caring has grown as technology and depersonalization of health care delivery have increased. Major concepts of the ethics of caring are reviewed, with special focus on relating caring and virtue ethics. Assuming that caring is a virtue, it is concluded that ethically virtuous nurses must possess the caring attributes and demonstrate caring actions.

Empathy↗
PubMed1992

Community health and ethical theory: implications for holistic nursing.

A conceptual shift from Enlightenment philosophies to communitarian virtues is discussed. Epidemics and preventing disease spread are used as a basis for discussing the major bioethical concepts beneficence, justice, respect for autonomy, and Moskop's principle of restrictive measures. The addition of the concept of community and communitarian virtues to the ethical analysis is discussed. Holistic nurses are challenged to develop and employ morally sound rationale for ethical decisions.

Beneficence↗
PubMed1992

Sudden infant death syndrome (SIDS) and the toxic gas hypothesis: microbiological studies of cot mattresses.

1. Fifty infants' mattresses were studied to investigate the occurrence of viable fungal and bacterial propagules, with particular reference to Scopulariopsis brevicaulis which had been suggested to be implicated in SIDS cases. A total of 19 SIDS cases mattresses, 1 non-SIDS death, 20 used controls, and 10 new unused controls were examined. 2. Differences were found between SIDS and used controls in the variety of fungal species isolated and the numbers isolated from fillings; bacterial numbers were similar. 3. S. brevicaulis was isolated from only four mattresses, three of which were SIDS cases. It was not found in most of those on which death had occurred. 4. A number of potentially pathogenic or allergenic fungi, including Aspergillus fumigatus, were isolated more frequently from SIDS cases mattresses than new or used controls. 5. Scanning electron microscopy of mattress covers and fillings showed microbial 'biofilms' in the head areas of all SIDS cases examined. This was not seen on other samples. 6. The limited number of mattresses studied and the use of unmatched controls precludes the drawing of any general conclusions as to the significance of the biofilms or other fungi isolated. 7. Reports of the existence of a dimorphism in general growth forms of S. brevicaulis were investigated by growing and transferring authentic strains between a variety of growth media. 8. No 'slimy' state of this fungus was observed and dimorphism was not confirmed.

Bacteria↗
PubMed1991

Extreme sexual dimorphism in a Miocene hominoid.

Some Miocene hominoids may have been extremely sexually dimorphic for body size, inferred from the apparent dimorphism of dental and gnathic remains. But this has never been demonstrated convincingly for any fossil species because of small sample sizes, uncertainties about the number of species in most fossil samples, and the inability to reliably sex individual specimens. Here we demonstrate a case of extreme dental dimorphism, and presumed body-size dimorphism, in a Miocene hominoid sample in which these limitations have been overcome. Lufengpithecus lufengensis from the late Miocene site of Lufeng, China, was more dimorphic than the most dimorphic living hominoid, the orangutan, and may have been more dimorphic than any living anthropoid.

Animals↗
PubMed1991

Digitally-directed transrectal biopsy using Biopty gun versus transrectal needle aspiration: comparison of diagnostic yield and comfort.

A technique for digitally-directed core biopsy using the Biopty device and prospective comparison of accuracy and comfort, using this technique simultaneously with transrectal needle aspiration, are presented. To better estimate the true prevalence of carcinoma in the study population, a repeat combined procedure was performed on all subjects who did not have carcinoma confirmed on the initial core biopsies. All procedures were done by one investigator and all pathology reviewed by one senior pathologist. A total of 180 combined procedures were performed on 100 consecutive patients with palpably abnormal prostates; 30 carcinomas were detected. Digitally-directed Biopty biopsy yielded a sensitivity rate of 87 percent compared with 57 percent for needle aspiration (p less than 0.05). Using a numerical comfort scale, the Biopty device was also rated less painful than needle aspiration (p = 0.0001). The morbidity of the combined procedure was minimal, with a minor complication rate of 2.2 percent. No infections occurred.

Aged↗
PubMed1991

Cytokine signaling in lung: transforming growth factor-beta secretion by lung fibroblasts.

Control of growth and phenotypic expression of interstitial fibroblasts is a critical determinant of lung architecture and physiology during processes of growth and remodeling. We examined the ability of lung fibroblasts to produce transforming growth factor-beta (TGF-beta), a cytokine that is known to modulate proliferation and phenotypic expression of mesenchymal cells. Cultures of fibroblasts isolated from rat lungs spontaneously secrete TGF-beta as measured in the standard bioassay of anchorage-independent growth of normal rat kidney (NRK) cells in soft agar. Rat lung fibroblasts secrete TGF-beta in an inactive precursor form. Fibroblasts cultured from adult and fetal rat lungs produced comparable amounts of TGF-beta. The ability of lung fibroblast supernatant fluids to induce colony formation in soft agar could be completely neutralized by preincubation of samples with anti-TGF-beta immunoglobulin (Ig). Anti-platelet-derived growth factor IgG had no effect on anchorage-independent growth of NRK cells driven by rat fibroblast culture supernatant samples. These results indicate that TGF-beta does not require the presence of and interaction with secondary cytokines for its activity. In contrast to the results obtained with rat cells, neither human fetal nor adult lung fibroblasts secreted detectable amount of active TGF-beta or its inactive precursor. This was not due to the presence of TGF-beta inhibitors in fibroblast culture media, because the addition of purified porcine TGF-beta to conditioned medium from human lung fibroblast cultures yielded the expected increase in NRK cell growth in soft agar. These results point to differing cytokine control patterns in the lungs of the two species.

Animals↗
PubMed1991

Effect of fasting on uteroplacental amino acid metabolism in the pregnant sheep.

In the fed state, the net utilization of most amino acids by the ovine uteroplacental unit (defined as uterine uptake minus umbilical uptake) is zero. This study was to determine if this is true for the fasted pregnant ewe also, when uteroplacental glucose uptake is diminished. Glucose and amino acid concentrations were determined in 9 pregnant ewes across the uterine and umbilical circulations. Uterine and umbilical blood flows were determined by the steady state antipyrine diffusion method, and net uptakes across each circulation calculated by application of the Fick principle. Five amino acids were found to have a consistently greater uterine uptake than umbilical uptake. In addition, glutamate had a negative net umbilical uptake coupled with no net uterine uptake. Fasting resulted in an increase in the differences between the respective uptakes for all five amino acids. No additional amino acids were found to have disparate uptakes than were seen in the fed state. Umbilical glutamate uptake became less negative during fasting, but the difference between the uterine and umbilical circulations remained unchanged, as the uterine circulation took up glutamate during fasting. The umbilical circulation took up alpha-ketoisocaproate 0.626 +/- 0.18, fed), and the uptake was increased during fasting (1.8 +/- 0.6). These findings suggest that the branched chain amino acids and glutamine are utilized by the ovine uteroplacenta to a greater degree than are most other amino acids, and at increased rates during fasting of the ewe. These amino acids, through deamination, may be the source of uteroplacental ammonia production, as well as serving as an energy substrate when glucose supply is limited.

Amino Acids↗
PubMed1991

Plasma cell pneumonia induced by Legionella pneumophila.

We report a case of severe Legionella pneumonia in which the histopathologic features of an open lung biopsy specimen were characterized by a monotypic plasma cell infiltrate and absence of granulocytes or other acute inflammatory cells. The clinical course was otherwise typical for a severe case of Legionella pneumonia with complete functional and roentgenographic recovery following a prolonged convalescence. We speculate on possible reasons for this patient's unusual histopathologic features.

Female↗