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Biomedical subjects

G Walker

Publications and source records attributed to G Walker.

At least 73 records · Page 4Linked to original sources
PubMed1996

Entry to care: positive choice or fait accompli? developing a more proactive nursing response to the needs of older people and their carers.

A range of issues surrounding admission to either residential or nursing home care are considered from the perspectives of older people and their family carers. Drawing on the literature and a number of studies conducted by the authors, the processes and perceptions that shape and influence admission to care are identified. On the basis of the interaction of these factors a four-stage typology of admission is suggested: the positive choice, the rationalized alternative, the discredited option, and the fait accompli. The characteristics of each admission type are discussed and the implications for professionals, particularly nurses, working with older people and their carers are addressed.

Aged↗
PubMed1996

Inhibition by tetranactin of interleukin 1 beta- and cyclic AMP-induced nitric oxide synthase expression in rat renal mesangial cells.

1. We have investigated whether tetranactin, a cyclic antibiotic produced by Streptomyces aureus with a molecular structure related to cyclosporin A, influences inducible nitric oxide synthase (iNOS; EC 1.14.13.39) induction in rat glomerular mesangial cells. 2. Previously we have shown that iNOS is expressed in renal mesangial cells in response to two principal classes of activating signals comprising inflammatory cytokines such as interleukin 1 (IL-1) or tumour necrosis factor alpha and agents that elevate cellular levels of cyclic AMP. Treatment of mesangial cells with IL-1 beta or the membrane-permeable cyclic AMP analogue, N6, 0-2'-dibutyryladenosine 3',5'-phosphate (Bt2 cyclic AMP) for 24 h induces iNOS activity measured as nitrite levels in cell culture supernatants by 44 fold or 33 fold, respectively. Incubation of mesangial cells with tetranactin inhibits IL-1 beta- and cyclic AMP-dependent production of nitrite in a dose-dependent fashion with IC50 values of 50 nM and 10 nM, respectively. 3. Western-blot analyses of mesangial cell extracts reveal that the inhibition of nitrite synthesis by tetranactin is due to a suppression of iNOS protein levels. This effect is preceded by a reduction of iNOS mRNA steady state levels as demonstrated by Northern blot analyses of total cellular RNA isolated from stimulated mesangial cells. 4. Thus, tetranactin is a potent inhibitor of iNOS expression in cytokine- and cyclic AMP-stimulated mesangial cells and represents a new class of iNOS inhibitors with IC50s in the low nanomolar range. This compound may be useful in the therapy of diseases associated with pathological NO overproduction due to iNOS expression.

Animals↗
PubMed1996

Fertilization promotes selective association of the Abl [correction of AbI] kinase with the egg cytoskeleton.

Fertilization of the sea urchin egg is known to involve activation of a variety of protein kinases including at least one protein tyrosine kinase. In the present study, fertilization was found to stimulate the association of the Abl [correction of AbI] protein kinase with the detergent-insoluble egg cytoskeleton. Increased levels of Abl protein and of protein tyrosine kinase activity were detected in cytoskeleton preparations made as early as 5 to 15 min after insemination. Immunofluorescence localization demonstrated that the Abl kinase becomes associated primarily with the cortical cytoskeleton of the fertilized egg. A separate, 57 kDa protein tyrosine kinase did not associate with the cytoskeleton indicating that fertilization results in the selective association of the Abl kinase with the cortical cytoskeleton.

Animals↗
PubMed1995

Interleukin 1 beta-induced expression of nitric oxide synthase in rat renal mesangial cells is suppressed by cyclosporin A.

The expression of inducible nitric oxide synthase (iNOS) is triggered in rat renal mesangial cells by exposure to the inflammatory cytokine interleukin 1 beta (IL-1 beta). Here we report that cyclosporin A (CsA) a potent immunosuppressive drug, inhibits IL-1 beta dependent iNOS expression in renal mesangial cells. Addition of CsA dose dependently suppresses IL-1 beta-induced nitrite formation (IC50 = 0.9 microM). Western- and Northern blot analyses of mesangial cell extracts reveal that the inhibition of IL-1 beta-induced nitrite formation by CsA is due to decreased iNOS protein and iNOS mRNA steady state levels. Using nuclear run on experiments we show that the transcription rate of the IL-1 beta-induced iNOS gene is reduced. Furthermore, by electrophoretic mobility shift analysis we demonstrate reduced DNA-binding of the nuclear factor NF kappa B, an essential component of the IL-1 beta-dependent upregulation of iNOS gene transcription. The data presented in this report suggest that the cellular machinery involved in the IL-1 beta dependent transcriptional upregulation of the iNOS gene in mesangial cells is a target for the action of CsA.

Animals↗
PubMed1995

Pyrrolidine dithiocarbamate differentially affects cytokine- and cAMP-induced expression of group II phospholipase A2 in rat renal mesangial cells.

Renal mesangial cells express group II phospholipase A2 in response to two principal classes of activating signals that may interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) and agents that elevate cellular levels of cAMP such as forskolin, an activator of adenylate cyclase. Using pyrrolidine dithiocarbamate (PDTC), a potent inhibitor of nuclear factor NF kappa B, we determined its role in cytokine--and cAMP--triggered group II PLA2 expression. Micromolar amounts of PDTC suppress the IL-1 beta- and TNF alpha-dependent, but not the forskolin-stimulated group II PLA2 activity in mesangial cells. Furthermore, PDTC inhibited the increase of group II PLA2 mRNA steady state levels in response to IL-1 beta and TNF alpha, while only marginally affecting forskolin-induced PLA2 mRNA levels. Our data suggest that NF kappa B activation is an essential component of the cytokine signalling pathway responsible for group II PLA2 gene regulation and that cAMP triggers a separate signalling cascade not involving NF kappa B. These observations may provide a basis to study the underlying mechanisms involved in the regulation of group II PLA2 gene expression.

Animals↗
PubMed1995

Effect of stress on interleukin-2 receptor expression by bovine mononuclear leukocytes.

Holstein calves given three consecutive i.m. injections of dexamethasone (DEX) (0.04 mg kg-1) showed lymphopenia and neutrophilia with increased numbers of mature neutrophils on post-injection Days 1 and 2, but these values returned to normal levels by post-injection Day 3. Interleukin-2 receptor (IL-2R) expression by peripheral blood mononuclear cells (PBMC) was evaluated by flow cytometry using a monoclonal antibody specific for bovine IL-2R alpha. Treatment with DEX significantly decreased expression of IL-2R alpha in Concanavalin A (Con A)-activated PBMC on Day 1 (P < 0.02) and on Day 2 (P < 0.1). On Day 3, expression of IL-2R alpha by PBMC was similar in control and DEX-treated calves. This decrease in IL-2R alpha expression correlated with decreased proliferative responses of PBMC to the T-cell mitogens, phytohemagglutinin (PHA) and Con A. Following in vitro treatment with recombinant human (rhu) interleukin-12 (IL-12) Con A-induced proliferative responses of PBMC tended to be higher in both groups. However, the rhu IL-12 induced increase of Con A activated proliferative responses were significantly greater in DEX-treated calves than in control calves. IL-2R alpha expression by PBMC was found to be less in calves transported 800 km in a truck as compared to that in PBMC from controls. These data suggest that stress-induced immunosuppression in calves may involve decreased IL-2R alpha expression and decreased IL-12 production. Serum chemistry results indicated a trend toward higher creatine kinase (CK) levels in DEX-treated calves. This may be due to the lysis of corticosteroid sensitive lymphocytes.

Animals↗
PubMed1995

The chemistry of pseudomonic acid. Part 14. Synthesis and in vivo biological activity of heterocyclyl substituted oxazole derivatives.

Semisynthetic analogues of pseudomonic acid A have been prepared containing a heterocyclyl substituted oxazole. Derivatives in which the heterocycle was thiophene, furan, pyridine, or isoxazole showed good antibacterial potency and were further evaluated in vivo. Both pharmacokinetic parameters and oral activity against an experimental intraperitoneal sepsis were superior to results obtained from previously described pseudomonic acid A derivatives.

Animals↗
PubMed1995

Disaster nursing in the Oklahoma City bombing.

The Oklahoma City Federal Building disaster quickly changed a routine day of eye surgical procedures into a chaotic trauma center for the victims with not only eye injuries, but multiple deep lacerations and other injuries. The devastating and disruptive effect of the bombing was stressful for the nursing staff who became disaster survivors of the emotional trauma involved.

Blast Injuries↗
PubMed1994

Incidence of familial melanoma and MLM2 gene.

The overall incidence of melanoma is increasing world wide. We investigated whether there has been an increase in familial melanoma by studying age at onset among different birth cohorts in 18 melanoma kindreds linked to a predisposition gene (MLM2) on chromosome 9. The cumulative incidence of melanoma was 21-fold higher (95% CI 5.2-84.6) among subjects born after 1959 than in those born before 1900. The expected age of onset of the group born after 1959 was 24 years earlier (21.0 vs 45.0 years). These data support the notion that phenotypic penetrance of the MLM2 gene is increasing, presumably as a result of the interaction of sunlight exposure and mutation at this locus.

Adolescent↗
PubMed1994

Dexamethasone differentially affects interleukin 1 beta- and cyclic AMP-induced nitric oxide synthase mRNA expression in renal mesangial cells.

Inducible nitric oxide synthase (iNOS) is expressed in renal mesangial cells in response to two principal classes of activating signals that interact in a synergistic fashion. These two groups of activators comprise inflammatory cytokines such as interleukin (IL)-1 beta or tumour necrosis factor alpha and agents that elevate cellular levels of cyclic AMP (cAMP). We examined whether dexamethasone differentially affects iNOS induction in response to IL-1 beta and a membrane-permeable cAMP analogue, N6,O-2'-dibutyryladenosine 3',5'-phosphate (Bt2cAMP). Nanomolar concentrations of dexamethasone suppress IL-1 beta- as well as Bt2cAMP-induced iNOS protein expression and production of nitrite, the stable end product of nitric oxide (NO) formation. In contrast, dexamethasone prevents induction of iNOS mRNA in response to Bt2cAMP without affecting IL-1 beta-triggered increase in iNOS mRNA levels. These data suggest that dexamethasone acts at different levels, depending on the stimulus used to suppress iNOS induction in mesangial cells.

Amino Acid Oxidoreductases↗
PubMed1994

Two distinct signaling pathways trigger the expression of inducible nitric oxide synthase in rat renal mesangial cells.

The expression of nitric oxide synthase (NOS; EC 1.14.13.39) is induced in rat glomerular mesangial cells by exposure to the inflammatory cytokine interleukin 1 beta (IL-1 beta) or cAMP-elevating agents. Stimulation with IL-1 beta alone leads to an approximately 40-fold increase in NOS activity and nitrite synthesis, whereas the elevation of cAMP with forskolin, cholera toxin, salbutamol, or dibutyryl-cAMP for 24 h resulted in a 2- to 12-fold increase in NOS activity. Moreover, the combinations of IL-1 beta with each of the cAMP-elevating agents greatly enhanced NOS activity in a synergistic fashion. Northern-blot analysis demonstrated a single band of approximately 4.5 kb for the NOS mRNA in rat mesangial cells. IL-1 beta increased NOS mRNA levels in a dose- and time-dependent fashion with a peak of NOS mRNA at 24 h. Dibutyryl-cAMP also increased NOS mRNA levels in mesangial cells in a dose- and time-dependent manner. Furthermore, combination of IL-1 beta and forskolin revealed a strong synergy with maximal mRNA levels 12 h after stimulation. Nuclear run-on transcription experiments suggest that IL-1 beta and cAMP synergistically interact to increase NOS gene expression at the transcriptional level. Furthermore, message stability studies established that NOS mRNA induced by cAMP has a longer half-life than the IL-1 beta-induced message. Moreover, cAMP exposure markedly prolonged the half-life of NOS mRNA from 1 h to 3 h. These data suggest that the level of NOS mRNA is controlled by at least two different signaling pathways, one involving cAMP and the other being triggered by cytokines such as IL-1 beta. The two pathways act synergistically and thus potently up-regulate the expression of inducible NOS in rat mesangial cells.

Amino Acid Oxidoreductases↗
PubMed1994

[Concentration of biocides in indoor rooms using pyrethroids as an example].

Pyrethroids are an analogous substance group to one of the oldest known, naturally occurring insecticides pyrethrum and have replaced a number of pesticides such as Lindane, DDT and PCP on the market. Biocides are more persistent indoors than in nature, which could lead to permanent health hazards for the people concerned. Within a few days after application pyrethroids are rarely detected in room air but can be traced for a long time on textiles, furniture and in dust particles (3, 8). The investigation results of approx. 100 analyses from dust and carpet samples show that approx. 1/3 of these samples are positive for at least one pyrethroid and contain a concentration of > 2 mg substance per kg sample. The evaluation of 35 air samples taken from rooms where substances containing pyrethroids had been used at least a month prior to the investigation (the samples were sampled on active charcoal or Chromosorb) showed that pyrethroids could no longer be traced above the detection limit of 0.05-0.1 micrograms/m3. We therefore think that when investigating a contamination of rooms by biocides it is more advisable to determine pyrethroid and its synergists in the suspended dust portion and corresponding dust sample rather than analysing air by adsorption to active charcoal, Chromosorb or other carrier materials. From the observed concentrations of biocides one could conclude that in an indoor setting secondary contamination by biocides plays a more significant role in the total-body-load than that of air contamination.

Air Pollution, Indoor↗
PubMed1993

Who cares for Missouri's Medicaid nursing home residents? Characteristics of attending physicians.

OBJECTIVE: To describe the characteristics of physicians attending Medicaid recipients in Missouri's certified nursing homes (NH). DESIGN: Retrospective survey of multiple data sources. SETTING: Missouri's certified nursing homes. PARTICIPANTS: 1,339 physicians attending 22,452 Medicaid recipients. MEASUREMENTS: Physician characteristics were determined by reviewing a roster of medical directors of NHs compiled by the Missouri Department of Social Services' Division of Aging and physician directories compiled by the Missouri State Board of Registration for the Healing Arts, the AMA, the AOA, the ABFP, and the ABIM. Physician clinical activity was determined by examining NH inspection of care reports compiled by the Missouri Department of Social Services' Division of Aging. RESULTS: Each physician attended a mean of 16.8 and a median of six Medicaid recipients in the nursing home. The skewed distribution is reflected by 426 (31.8%) of the physicians attending only one or two residents, and 28 (2.1%) of the physicians attending 100 or more residents. Twenty-seven percent of the state's licensed osteopaths (DOs, 362) attended nursing home patients, compared with 11% of allopathic physicians (MDs, 977). Significantly more DOs than MDs attended more than the median number of patients (57% vs 45%, P < 0.001). Half were attended by the 605 (45%) physicians without board certification. Of those who were board certified, family physicians were more likely to include Medicaid nursing home patients in their practices than internists (43% vs 18%, P < 0.001). Physicians licensed for 11 to 20 years and rural physicians had the heaviest patient loads. CONCLUSIONS: Many doctors are caring for very few nursing home residents while a few doctors may be caring for too many patients. In addition, half the Medicaid recipients residing in Missouri's nursing homes in 1988 were attended by physicians without board certification, and almost one-third were attended by physicians who may be retiring between 2000 and 2010.

Aged↗