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Biomedical subjects

M Gray

Publications and source records attributed to M Gray.

At least 19 recordsLinked to original sources
PubMed2000

Endothelin-1 stimulates cardiac fibroblast proliferation through activation of protein kinase C.

After myocardial ischemia, circulating levels of the mitogen endothelin-1 (ET-1) increase. The effects of ET-1 on cardiac fibroblasts are poorly characterized. Therefore we examined the influence of ET-1 on cardiac fibroblast proliferation with a view to elucidating the signal transduction mechanisms underlying this effect. ET-1 (10 n m) stimulated [(3)H]thymidine incorporation and cell proliferation in cultured neonatal rat cardiac fibroblasts, consistent with its activity as a mitogen. We examined the role of protein kinase C (PKC) on this function. Inhibition of PKC activation with either chelerythrine (1 microm) or staurosporine (1 n m) attenuated ET-1-induced increases in DNA synthesis and cell number. Downregulation of PKC by chronic pretreatment with 10 n m phorbol 12-myristate 13-acetate (PMA) also prevented ET-1-induced mitogenesis. In contrast to previous reports that cardiac fibroblast proliferation stimulated by angiotensin II acts independently of PKC, the ET-1 mediated mitogenic effect requires activation of PKC in these cells. Findings in adult rat cardiac fibroblasts were identical. In addition, we noted that concurrent treatment with the pro-inflammatory cytokine interleukin 1 beta which, like ET-1, is released after myocardial ischemia, attenuated the ET-1-induced increases in DNA synthesis and cell number. This effect was not mediated through a nitric oxide synthase pathway.

Alkaloids↗
PubMed2000

A brief history of advanced practice nursing and its implications for WOC advanced nursing practice.

Although the evolution of clinical nurse specialists and nurse practitioners during the previous several decades has led to a sense of novelty regarding advanced practice, it is important to remember that nurses have engaged in such roles for nearly 100 years. This article will review the history of advanced nursing practice, summarize current definitions of specialty and advanced practice, discuss the evolution of advanced practice and its impact on contemporary nursing, and provide a background for advanced practice considerations for the WOC nurse, which are discussed in detail in subsequent articles by Janice Beitz (pp 55-64) and Dorothy Doughty (pp 65-8) in this issue.

History, 20th Century↗
PubMed2000

Continence for women: evaluation of AWHONN's third research utilization project.

OBJECTIVE: To develop an evidence-based protocol for initial evaluation and treatment of urinary incontinence and to design procedures that would facilitate the protocol's implementation into clinical practice. DESIGN: Descriptive report of the Association of Women's Health, Obstetric and Neonatal Nurses (AWHONN) Continence for Women Project. SETTING: Twenty-one public, private, and other women's health sites. Participants: Women in ambulatory care settings (N = 1474) provided demographic statistics. METHODS: The protocol was developed, sites were selected, site coordinator training was provided, data collection was facilitated by project-specific teleforms, and the overall process was evaluated by the science team. MAIN OUTCOME MEASURES: Site representation, patient representation, site coordinator feedback on the training program, and site coordinator experience during project implementation. RESULTS: The process yielded a representative mix of site and patient diversity appropriate for testing of the protocol. Site coordinators felt well-prepared to implement the protocol and experienced increased professional satisfaction because of therapeutic benefits achieved for patients and positive collaboration with physicians. CONCLUSIONS: The Continence for Women Project demonstrated the potential for developing and testing evidence-based protocols for clinical practice when the resources of an organization such as AWHONN and the research community are combined.

Journal Article↗
PubMed2000

Continence for women: a test of AWHONN's evidence-based protocol in clinical practice.

OBJECTIVE: To test the effectiveness of an evidence-based protocol for urinary incontinence in increasing identification of women with the condition and improving their outcomes. DESIGN: Prospective formative evaluation study. SETTING: Twenty-one public, private, and other women's health care sites. PARTICIPANTS: Women in ambulatory care settings (N = 1474) provided descriptive statistics. Clinical outcomes were tested in 132 cases for whom pre- and posttreatment data were available. INTERVENTIONS: Standardized screening and baseline follow-up forms were used to minimize time burden on clinicians; bladder and pelvic floor muscle training materials were provided to clinicians for distribution. MAIN OUTCOME MEASURES: Self-reported frequency, volume, and quality of life related to incontinence and cost of self-management were used to assess protocol effectiveness. RESULTS: Frequency of incontinence episodes, estimated volume lost per episode, and the cost of self-management decreased. Quality of life improved, as reflected in decreased bother attributed to incontinence and in the number of women avoiding activities such as shopping, exercising, or travel because of incontinence. CONCLUSIONS: This simple program of pelvic floor muscle and bladder training, as it has been systematically implemented in a variety of ambulatory women's health care settings, has benefitted women's continence status. The results of this project strongly support widespread application.

Journal Article↗
PubMed2000

Repeat sizes at CAG/CTG loci CTG18.1, ERDA1 and TGC13-7a in schizophrenia.

A number of studies using the repeat expansion detection (RED) technique have suggested an association between unknown large CAG/CTG repeats and schizophrenia. The polymorphic CAG/CTG repeat loci CTG18.1 and ERDA1 have been reported to account for a high proportion (approximately 90%) of the large repeats detected by RED and may therefore be responsible for the cited association. The recently described locus TGC13-7a contains a highly polymorphic CTA/TAG and CAG/CTG composite repeat, and is thus another authentic candidate. In the present investigation, each locus was analysed for association with schizophrenia in a sample of 206 patients and 219 group-matched controls. No evidence for association of CTG18.1, ERDA1 and/or TGC13-7a with schizophrenia was found. The combined data accounted for only 54% of the CAG/CTG arrays of > 40 repeats found in our previous RED analysis.

Adult↗
PubMed2000

No evidence for association between a non-synonymous polymorphism in the gene encoding human metabotropic glutamate receptor 7 and schizophrenia.

The cDNA sequence of the gene encoding human metabotropic glutamate receptor type 7 (mGluR7) contains the single nucleotide polymorphism 1536A > T [GenBank sequence X94552 (Makoff et al., 1996)]. This sequence variation is predicted to result in an amino acid change (F433Y) in the gene product and thus has the potential to affect receptor function. Since disturbances in glutamate function have been implicated in the pathophysiology of schizophrenia, we have used a novel and robust polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to genotype this polymorphism in a case-control sample comprising 181 schizophrenic patients and 182 group-matched unaffected individuals. No evidence was found for association between this polymorphism and schizophrenia. We have also localised mGluR7 to chromosome 3p25-22 using radiation hybrid (RH) mapping.

Alleles↗
PubMed2000

Maintenance of androdioecy in the freshwater shrimp, Eulimnadia texana: estimates of inbreeding depression in two populations.

Androdioecy is an uncommon form of reproduction in which males coexist with hermaphrodites. Androdioecy is thought to be difficult to evolve in species that regularly inbreed. The freshwater shrimp Eulimnadia texana has recently been described as both androdioecious and highly selfing and is thus anomalous. Inbreeding depression is one factor that may maintain males in these populations. Here we examine the extent of "late" inbreeding depression (after sexual maturity) in these clam shrimp using two tests: (1) comparing the fitness of shrimp varying in their levels of individual heterozygosity from two natural populations that differ in overall genetic diversity; and (2) specifically outcrossing and selfing shrimp from these same populations and comparing fitness of the resulting offspring. The effects of inbreeding differed within each population. In the more genetically diverse population, fecundity, size, and mortality were significantly reduced in inbred shrimp. In the less genetically diverse population, none of the fitness measures was significantly lowered in selfed shrimp. Combining estimates of early inbreeding depression from a previous study with current estimates of late inbreeding depression suggests that inbreeding depression is substantial (delta = 0.68) in the more diverse population and somewhat lower (delta = 0.50) in the less diverse population. However, given that males have higher mortality rates than hermaphrodites, neither estimate of inbreeding depression is large enough to account for the maintenance of males in either population by inbreeding depression alone. Thus, the stability of androdioecy in this system is likely only if hermaphrodites are unable to self-fertilize many of their own eggs when not mated to a male or if male mating success is generally high (or at least high when males are rare). Patterns of fitness responses in the two populations were consistent with the hypothesis that inbreeding depression is caused by partially recessive deleterious alleles, although a formal test of this hypothesis still needs to be conducted.

Animals↗
PubMed2000

Anion interactions with CFTR and consequences for HCO3- transport in secretory epithelia.

We have been studying CFTR channels in guinea pig pancreatic duct cells and rather surprisingly found that luminal HCO3- had a pronounced inhibitory effect on cAMP-activated CFTR chloride currents. The block produced by HCO3- was rapid, voltage-independent and occurred over a physiological range of extracellular HCO3- concentrations. I- and ClO4- were also found to inhibit CFTR currents, but both were less effective than HCO3-. Although we have not identified how HCO3- is able to block CFTR our data suggests that an external anion-binding site on the channel itself is involved. Overall, our results show that luminal HCO3- acts as a potent inhibitor of CFTR channels (and by inference CFTR-mediated secretion), under normal physiological conditions. These data have implications not only for current models of pancreatic duct cell HCO3- transport, but also for other bicarbonate-secreting tissues, such as the liver, GI tract and lungs.

Animals↗
PubMed2000

Voiding dysfunction after radiation to the prostate for prostate cancer.

Radiation therapy is an increasingly common treatment for prostate cancer. Although radiotherapy is generally effective, it is not free of complications. Acute adverse effects of radiation are usually mild and managed on an outpatient basis. In contrast, long-term complications, although uncommon, may be debilitating or even life-threatening, requiring more invasive treatments or hospitalization. This article will review the pathophysiology of the acute and long-term effects of radiation on the lower urinary tract and implications for WOC nursing management of patients with voiding dysfunction following radiation therapy for prostate cancer.

Cystitis↗
PubMed1999

CAG repeat length in the hKCa3 gene and symptom dimensions in schizophrenia.

BACKGROUND: Long CAG repeats in the hKCa3 potassium channel gene have been associated with schizophrenia. We sought evidence for associations between this polymorphism and aspects of the schizophrenia phenotype. METHODS: Associations were investigated between CAG repeat length and gender, age of illness onset, and psychotic symptom dimensions in 203 unrelated individuals with DSM-IIIR schizophrenia. RESULTS: No association was found between CAG repeat length and gender or age of onset. Long CAG repeats were associated with higher negative symptom dimension scores. CONCLUSIONS: This study provides preliminary evidence that genetic liability to negative symptoms in schizophrenia may be partly mediated through the hKCa3 gene.

Adult↗
PubMed1999

Analysis of the capacity of extracts from normal human young and senescent fibroblasts to support DNA synthesis in vitro.

Cytoplasmic extracts from early-passage (young), late-passage (senescent) normal human fibroblast (HF) cultures and immortalized human cell lines (HeLa, HT-1080, and MANCA) were analyzed for their ability to support semiconservative DNA synthesis in an in vitro SV40-ori DNA replication system. Unsupplemented extracts from the three permanent cell lines were demonstrated to be active in this system; whereas young HF extracts were observed to be minimally active, and no activity could be detected in the senescent HF extracts. The activity of these extracts was compared after supplementation with three recombinant human replication factors: (1) the catalytic subunit of DNA polymerase alpha (DNA pol-alpha-cat), (2) the three subunits of replication protein A (RPA), and (3) DNA topoisomerase I (Topo I). The addition of all three recombinant proteins is required for optimum activity in the young and senescent HF extracts; the order of the level of activity is: transformed > young HF > senescent HF. Young HF extracts supplemented with RPA alone are able to support significant replicative activity but not senescent extracts which require both RPA and DNA pol-alpha-cat for any detectable activity. The necessary requirement for these factors is confirmed by the failure of unsupplemented young and senescent extracts to activate MANCA extracts that have been immunodepleted of DNA pol-alpha-cat or RPA. Immunocytochemical studies revealed that RPA, DNA pol-alpha, PCNA, and topo I levels are higher in the immortal cell types used in these studies. In the HF cells, levels of DNA pol-alpha-cat and PCNA are higher (per mg protein) in the low-passage than in the senescent cells. By contrast, RPA levels, as determined by immunocytochemical or Western blot studies, were observed to be similar in both young and senescent cell nuclei. Taken together, these results indicate that the low to undetectable activity of young HF extracts in this system is due mainly to reduced intracellular levels of RPA, while the senescent HF extracts are relatively deficient in DNA polymerase alpha and probably some other essential replication factors, as well as RPA. Moreover, the retention of RPA in the senescent HF nuclei contributes to the low level of this factor in the cytoplasmic extracts from these cells.

Blotting, Western↗