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Biomedical subjects

S L Howell

Publications and source records attributed to S L Howell.

At least 19 recordsLinked to original sources
PubMed1999

The p38 mitogen-activated protein kinase cascade is not required for the stimulation of insulin secretion from rat islets of Langerhans.

The expression of the p38 subfamily of mitogen-activated protein kinases (MAPKs) was examined in rat islets of Langerhans and pancreatic beta-cell lines, and its involvement in the regulation of insulin secretion was investigated. Rat islets and several rodent beta-cell lines were shown to express p38 MAPK by Western blotting. The cellular stress agents sodium arsenite and hyperosmotic sorbitol significantly stimulated p38 MAPK activity, as did the tyrosine phosphatase inhibitor sodium pervanadate and the serine/threonine phosphatase inhibitor okadaic acid. Increases in p38 MAPK activity were not consistently correlated with increases in insulin secretion, and the dissociation between p38 MAPK activity and the regulation of insulin secretion was further demonstrated in studies using the specific p38 MAPK inhibitor SB203580, which was without significant effect on the stimulation of insulin secretion by glucose, 4beta phorbol myristate acetate and forskolin. These studies indicate that although p38 MAPK is expressed in pancreatic beta-cells and can be activated pharmacologically, its activity can be dissociated from the exocytotic release of insulin from rat islets of Langerhans.

Animals↗
PubMed1998

Promoting nurses' positive attitudes toward cancer prevention/screening.

BACKGROUND: From 1991 to 1994, a special projects grant to teach nurses cancer prevention/screening theory and clinical skills was developed, implemented, and evaluated. Approximately 60 nurses in Colorado rural settings attended five two-day training sessions over a 20-month period. Attitudes, constructive or destructive, regarding specific behaviors lead to intentions to perform those behaviors and have an important impact on cancer-related nursing practice. METHODS: Two cancer-related attitude scales, Cancer Prevention/Early Detection Attitude Inventory and Fanslow Cancer Attitudes Scale, were administered prior to the first training session, following the final session, and at six-month follow-up. Data reflecting program impact on nursing practice were obtained from follow-up self-assessment of confidence in implementing new knowledge and skills. RESULTS: Significant differences in pre- and post-training attitude scores and fairly high-level confidence ratings suggest that these nurses will continue to use their cancer prevention and detection skills in practice. CONCLUSION: Documentation of practice activities to date has been impressive.

Adult↗
PubMed1997

Glucose-stimulated insulin secretion from rat islets of Langerhans is independent of mitogen-activated protein kinase activation.

The role played by mitogen-activated protein kinases (MAPKs) in the regulation of insulin secretion from adult rat islets of Langerhans was investigated by examining the effects of glucose, forskolin and 4beta phorbol myristate acetate (PMA) on islet MAPK activity and by measuring insulin secretion from islets in response to these agonists after inhibition of MAPK by PD 098059 (PD). Glucose (20mM) had a small (<2-fold) stimulatory effect on MAPK activity in isolated islets, and this was potentiated by forskolin (10 microM) and PMA (500nM), which also significantly stimulated MAPK activity at 2mM glucose. Pretreatment of islets with 50 microM PD inhibited MAPK activity, but had no effect on secretory responses to glucose, forskolin and PMA. These results suggest that although MAPK may be activated by insulin secretagogues in adult rodent islets, this can be dissociated from the exocytotic release of insulin.

Animals↗
PubMed1996

Identification and localisation of a type IV cytosolic phospholipase A2 in rat pancreatic beta-cells.

The liberation of arachidonic acid (AA), by phospholipase A2 (PLA2), is the rate-limiting step in a number of cell signalling pathways. In the pancreatic beta-cell, AA itself is thought to participate in the regulation of insulin secretion. Recently a Ca(2+)-sensitive, AA-selective cytosolic PLA2 (type IV cPLA2) has been isolated from the human monocyte U937 cell line. Although the DNA sequence of this enzyme implies a molecular weight of 85 kDa, the protein migrates with a molecular weight of 100-110 kDa on SDS-PAGE. In many cell types, cPLA2s which are reactive towards antibodies raised against the type IV cPLA2 have been shown to hydrolyse AA from membrane glycerophospholipids. Using a polyclonal antibody raised against a recombinant form of type IV cPLA2, we have detected an immunoreactive protein with a molecular weight of 93.5 kDa in rat islets of Langerhans. Furthermore, we have detected similar immunoreactive proteins in insulin-secreting beta-cell lines and have shown co-expression of type IV cPLA2 immunoreactivity and insulin immunoreactivity in rat pancreatic beta-cells. Under non-stimulatory conditions the 93.5 kDa immuno-reactive protein detected in rat islets of Langerhans was located predominantly in the cytosolic fraction. We have shown that immunoprecipitation of the rat immunoreactive protein from rat islet homogenates significantly decreases the total dithiothreitol/beta-mercaptoethanol-insensitive PLA2 activity by 56.4 +/- 7%. This provides further evidence that the immunoreactive rat protein is a type IV cPLA2 and is responsible for a large component of the PLA2 activity in rat islets of Langerhans. It is possible that, in the rat beta-cell, type IV cPLA2 couples the increase in intracellular Ca2+, brought about by insulin secretagogues, to the liberation of AA and the subsequent release of insulin.

Animals↗
PubMed1996

Evaluating a pediatric pain management research utilization program.

Research-based pain assessment and management innovations are not fully utilized in clinical nursing practice. Thus children continue to suffer despite strategies that could eliminate or significantly reduce their pain. An educational program was developed and implemented to integrate state-of-the-art pain assessment and management strategies into the clinical practice of pediatric nurses. This article reports on evaluation of the research utilization process during development and implementation of the program. The program included formal classes, development of instruments for pain assessment and documentation, ongoing consultation on pain management strategies, and designation of a unit-based staff nurse liaison. Findings illuminated the process through which nursing staff on one unit came to learn about new ideas, try those ideas in their clinical practice, re-invent certain strategies to better meet their needs, and, ultimately, to adopt innovations deemed helpful in their work.

Adult↗
PubMed1995

Protein phosphorylation in the regulation of insulin secretion: the use of site-directed inhibitory peptides in electrically permeabilised islets of Langerhans.

We have used electrically permeabilised rat islets of Langerhans to investigate the role of protein phosphorylation in the regulation of insulin secretion using pseudosubstrate inhibitory peptides for cyclic AMP-dependent protein kinase (PKA) and for protein kinase C (PKC). The protein kinase inhibitor (PKI) peptide, PKI(6-22), completely inhibited the effects of cyclic AMP on islet PKA activity in vitro, on endogenous protein phosphorylation and on insulin secretion. This peptide had no significant effect on islet PKC activity in vitro, on Ca(2+)-induced protein phosphorylation and on secretory responses to Ca2+ or to the PKC activator, 4 beta-phorbol myristate acetate (PMA). The PKC pseudosubstrate inhibitory peptide, PKC(19-36), caused a marked inhibition of islet PKC activity in vitro and inhibite PMA-induced insulin secretion without affecting secretory responses to cyclic AMP and Ca2+. These results demonstrate that PKA- and PKC-induced protein phosphorylation is obligatory for cyclic AMP- and PMA-stimulated insulin secretion, respectively, and suggest that there is little "crosstalk" between the response elements of the secretory pathways to the different second messengers, at least after the generation of the messengers within the beta-cells.

Adenosine Triphosphate↗
PubMed1995

Insulin secretion from islets of GK rats is not impaired after energy generating steps.

Insulin secretory responses of intact and electrically permeabilised islets of Goto-Kakizaki (GK) rats, a novel model of non-insulin dependent diabetes mellitus, and Wistar (control) rats were compared to investigate the mechanism of the impairment of insulin secretion from pancreatic islets of GK rats. Insulin secretion from intact islets in response to glucose, glyceraldehyde, succinate monomethylester and tetramethyl p-phenylenediamine, which reduces cytochrome c directly, was significantly impaired in GK rats compared to control rats (P < 0.05, P < 0.01, P < 0.05 and P < 0.05, respectively). However, Ca(2+)-induced insulin release from electrically permeabilised islets of GK rats was higher than that of control rats. Moreover, insulin secretion from intact islets in response to 50 mM KCl, which depolarises islet cells, was not impaired in GK rats. These results indicate that insulin secretion from islets of GK rats is not impaired after energy generating steps of metabolism.

Animals↗
PubMed1995

Severity-adjusted differences in hospital utilization by gender.

Gender-based differences in hospital use may result from biological differences or may suggest problems of access to health services and quality of care. We hypothesized that there should be no difference in hospital care between men and women, given the same diagnosis. Hospitalizations were characterized by severity of illness, as this may indicate the timeliness of hospital care. Hospitalizations may be too late (with higher severity of illness) resulting in long stays and high costs, or too early (with lower severity of illness) resulting in care that could be given in alternative treatment settings. Three abdominal conditions were examined which could be misdiagnosed or confused with other diseases involving the female reproductive system: appendicitis, diverticulitis, and cholecystitis. The National Hospital Discharge Survey (NHDS) was used for analysis. Disease staging was used to assign a severity of illness indicator, ranging from stage 1 (conditions with no complications) to stage 3 (multiple site involvement, poor prognosis). For each disease, the percentage of discharges and the age-adjusted discharge rate per 1000 population was examined by stage of illness and gender. For appendectomy, there was a significantly greater percentage of men at stage 1 (lower severity) compared to women (73% versus 67%). For diverticular disease, women had higher proportions of stage 2/3 discharges than men for both medical and surgical hospitalizations. For cholecystitis, women had a greater percentage of hospitalizations at stage 1 than men, notably for surgical treatment (63% compared with 38%), although more men were admitted at stage 2 for both medical and surgical treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnostic Tests, Routine↗
PubMed1994

Regulation of insulin secretion: the role of second messengers.

This review summarises briefly studies performed in the last 5-6 years concerning the role of second messengers in the regulation of insulin secretion, using intact and electrically permeabilized rat islets of Langerhans. It is concluded that cyclic AMP (through protein kinase A), calcium (through calcium-calmodulin dependent protein kinases) and diacylglycerol (through protein kinase C) may be important second messengers in modulating the effects of specific secretagogues on insulin release. However, recent studies strongly suggest that neither protein kinase A nor protein kinase C are directly involved in the regulation of insulin secretion by glucose. The possible involvement of other second messengers, nitric oxide and arachidonic acid, in the regulation of secretion is also briefly reviewed.

Animals↗
PubMed1994

Natural/alternative health care practices used by women with chronic pain: findings from a grounded theory research study.

Findings from a grounded theory research study provide insights into making health care practices more beneficial for the needs and concerns of women with chronic pain. This article focuses on how healthy women advantageously used natural/alternative health care and pain management practices. The "healthiest" women primarily used self-care with a wide, holistic range of natural/alternative modalities.

Adult↗
PubMed1993

The mechanism of arachidonic acid-induced insulin secretion from rat islets of Langerhans.

The stimulation of rat pancreatic islets by glucose leads both to the secretion of insulin, and the production of arachidonic acid (AA). We have previously shown that exogenous AA can stimulate insulin secretion and that this secretion was not dependent upon extracellular Ca2+ nor upon the activation of protein kinase C. We have now demonstrated that AA-induced insulin secretion was a saturable and reversible process. AA-stimulated insulin secretion was slow in onset from intact islets but immediate from electrically permeabilized islets. In permeabilized islets AA-induced insulin secretion was not dependent on changes in intracellular Ca2+ or ATP and was not inhibited by noradrenaline. These results suggest that AA affects insulin secretion at a late stage in the exocytotic process.

Animals↗
PubMed1993

Activation of protein kinase C partially alleviates noradrenaline inhibition of insulin secretion.

The sympathetic neurotransmitter noradrenaline (NA) fully inhibited both phases of glucose-stimulated insulin secretion from rat islets of Langerhans. The secretory response to the protein kinase C (PKC) activator, 4 beta-phorbol myristate acetate (4 beta PMA), in the absence of exogenous glucose was also abolished by NA. However, at 20 mM glucose 4 beta PMA partially alleviated the inhibitory effect of NA both on insulin release and on cyclic AMP generation. Inhibition of insulin release by NA, albeit much decreased, was still observed in the presence of maximal stimulatory concentrations of both 4 beta PMA and dibutyryl cyclic AMP. The relieving effect of 4 beta PMA on the inhibition of insulin secretion by NA was not overcome by the competitive antagonist of cyclic AMP-dependent protein kinase, Rp-adenosine 3',5'-cyclic phosphorothioate. Down-regulation of islet PKC activity by overnight exposure to 4 beta PMA did not affect the inhibitory capacity of NA. These results suggest that NA inhibits insulin release independently of interaction with PKC, but that activation of this enzyme decreases the inhibitory effect of NA at stimulatory concentrations of glucose. This protective effect of 4 beta PMA could not be attributed to a decrease in NA inhibition of cyclic AMP generation.

1-Methyl-3-isobutylxanthine↗
PubMed1993

The role of protein kinase C in insulin biosynthesis.

Activation of protein kinase C (PKC) by the phorbol ester 4 beta-phorbol myristate acetate (4 beta-PMA) stimulated (pro)insulin biosynthesis in collagenase-isolated rat islets of Langerhans, as assessed by measuring the incorporation of [35S]cysteine into proinsulin and insulin after fractionation by high performance liquid chromatography. The stimulatory effects of 4 beta-PMA were observed at a substimulatory concentration of glucose (2 mM) but were not additive to the stimulatory effects of 20 mM glucose on insulin biosynthesis. Prolonged exposure to 4 beta-PMA caused a marked down-regulation of PKC activity in islets. PKC-depleted islets showed a much reduced biosynthetic response to 20 mM glucose, but this was caused, at least in part, by an enhanced basal rate of (pro)insulin synthesis. These elevations in the basal rate of insulin synthesis were not secondary to an increase in the amount of preproinsulin mRNA in PKC-depleted islets since Northern blot analysis showed that prolonged exposure to 4 beta-PMA, and the subsequent loss of PKC activity, did not detectably alter basal levels of preproinsulin mRNA. These results suggest that the activation of PKC stimulates (pro)insulin synthesis in rat islets by enhancing translation of existing preproinsulin mRNA, and that this may play some part in the biosynthetic responses of beta-cells to glucose.

Animals↗
PubMed1993

Staurosporine inhibits protein kinases activated by Ca2+ and cyclic AMP in addition to inhibiting protein kinase C in rat islets of Langerhans.

Staurosporine has been used in several studies to investigate the role of protein kinase C (PKC) in secretory responses of islets of Langerhans to insulin secretagogues. We have assessed the effect of staurosporine on: [i] islet PKC activity in vitro; [ii] the stimulation of insulin secretion by nutrient secretagogues and [iii] the stimulation of protein phosphorylation and insulin secretion in electrically permeabilised islets. All experiments were carried out on rat isolated islets of Langerhans, either intact or permeabilised by high voltage discharge (3.4 kV/cm). The activity of PKC partially purified from rat islets was inhibited by staurosporine (1.6-400 nM) in a concentration-dependent manner. Staurosporine also inhibited insulin secretion stimulated by both glucose and glyceraldehyde, with maximal effects at 50 nM. After prolonged exposure of islets to the tumour-promoting phorbol ester, 4 beta phorbol myristate acetate (4 beta PMA), a procedure which depletes islet PKC activity, staurosporine still inhibited both glucose- and glyceraldehyde-stimulated insulin release. In electrically permeabilised islets, staurosporine inhibited both Ca(2+)- and cyclic AMP-stimulated protein phosphorylation and insulin secretion. These results suggest that staurosporine should not be used as a selective inhibitor of PKC in rat islets.

Alkaloids↗