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Biomedical subjects

K Schaffer

Publications and source records attributed to K Schaffer.

12 recordsLinked to original sources
PubMed2001

[The efficacy of an individualized treatment schedule to maintain treatment adherence in an urban community mental health center].

OBJECTIVE: We present an observational study on the efficacy of an individualized treatment schedule, which is meant to support treatment adherence in an urban community mental health center (CMHC). METHODS: The present investigation was carried out in the natural setting of a CMHC in Vienna. During a 3-month period we observed the compliance with the appointments and the actions taken by the team in response to missed appointments as well as the utilization of the CMHC during a follow-up period of 6 months. RESULTS: During the observation period 393 (19,2 %) of 2049 scheduled visits were missed affecting more than half of the patients. Only a minority of patients with low-intensity treatment and a high rate of missed appointments had a high risk for discontinuing treatment. CONCLUSIONS: Missed appointments in outpatient psychiatric care are a common phenomenon but they constitute no major threat to the continuity of care for the majority of the patients due to the graduated efforts of the team. The time required to make up for missed appointments is considerable but the results of the follow-up confirmed the beneficial effects on utilization of psychiatric care.

Adult↗
PubMed2000

CCK receptor polymorphisms: an illustration of emerging themes in pharmacogenomics.

Polymorphisms in G-protein-coupled receptors can alter drug affinity and/or activity. In addition, genetic differences in amino acid sequences can induce ligand-independent signaling, which in turn can lead to disease. With growing efforts in the field of pharmacogenomics, it is anticipated that polymorphism-induced alterations in drug and/or receptor function will be a focus of increasing concern during the course of future drug-development efforts. In this review, the spectrum of pharmacological consequences that result from polymorphisms in the cholecystokinin CCK2 receptor will be discussed, thereby illustrating emerging themes in pharmacogenomics.

Amino Acid Sequence↗
PubMed1998

Interspecies polymorphisms confer constitutive activity to the Mastomys cholecystokinin-B/gastrin receptor.

The enteroendocrine hormone, gastrin, exerts trophic effects on the gastric mucosa through the CCK-B/gastrin receptor (CCK-BR). To varying degrees in different species, excess circulating gastrin leads to proliferation of enterochromaffin-like cells and to the development of gastric carcinoid tumors. The African rodent, Mastomys natalensis, is distinguished from other mammals by its propensity toward CCK-BR-mediated growth even in the absence of hypergastrinemia. Here, we report that the Mastomys CCK-BR, when expressed in COS-7 cells, differs from the respective human, canine, and rat receptor homologs by its ability to trigger ligand-independent (i.e., constitutive) inositol phosphate formation. To define the molecular basis of this observation, a series of Mastomys-human chimeric receptors was investigated. Functional characterization of these constructs revealed that a limited segment of the Mastomys CCK-BR, transmembrane domain VI through the C-terminal end, is sufficient to confer constitutive activity to the human protein. Mutagenesis studies within this CCK-BR region defined a combination of three Mastomys amino acids that, when introduced into the human receptor, together conferred a level of ligand-independent signaling comparable with the Mastomys CCK-BR. Complementing prior observations that single point mutations can lead to ligand-independent signaling, our findings suggest that multiple naturally occurring amino acid polymorphisms and/or mutations may together result in an enhanced basal level of receptor activity.

Animals↗
PubMed1997

Bombesin-like peptides stimulate somatostatin release from rat fundic D cells in primary culture.

In several species, bombesin-like neuropeptides stimulate somatostatin release in in vitro preparations of gastric mucosa. We sought to determine if this response is due to a direct effect on fundic D cells. Rat fundic mucosal cells were isolated by pronase E (1% D cells). D cells were separated by counterflow elutriation and subsequent density-gradient centrifugation (Nycodenz) (15% D cells) and grown in primary culture for 48 h (46% D cells). Cultured cells were double stained with affinity-purified rabbit-anti-gastrin-releasing peptide (GRP) receptor antibody and mouse monoclonal antibody to human somatostatin. After incubation with rhodamine-labeled anti-rabbit and fluorescein isothiocyanate-labeled anti-mouse antibodies, reactions were visualized by fluorescence microscopy. All cells positive for somatostatin had GRP receptors, whereas all non-D cells showed no expression in this G cell-free culture system. Somatostatin release from cultured cells was stimulated by sulfated cholecystokinin octapeptide (CCK-8; EC50 3 X 10(-10) M) and epinephrine (EC50 4 X 10(-8) M), which are established stimuli for canine fundic D cells. Bombesin (EC50 6 X 10(-11) M), its mammalian analog GRP-27, and neuromedin C (GRP-10) (EC50 1 X 10(-10) M, for both) were almost equally potent stimuli of somatostatin release, eliciting maximal response at 10(-9) M (400-550% above basal). Neuromedin B was less potent and effective (maximal response at 10(-8) M, 230% above basal). [D-Phe6]bombesin-(6-13)-OMe, a specific bombesin receptor antagonist, inhibited bombesin-stimulated somatostatin release in a competitive manner (IC50 9 X 10(-8) M). Potentiating interactions were observed between bombesin and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP) or epinephrine, but not between bombesin and CCK-8. We conclude that bombesin-like peptides directly stimulate somatostatin release by interacting with specific receptors on rat fundic D cells. Bombesin-like peptides appear to induce Ca(2+)-phospholipid-dependent signal-response transduction, as is indirectly suggested by potentiating interactions with DBcAMP or epinephrine.

Animals↗
PubMed1996

Gastrin secretion from primary cultures of rabbit antral G cells: stimulation by inflammatory cytokines.

BACKGROUND & AIMS: In Helicobacter pylori-induced gastritis, local production of cytokines may favor hypergastrinemia as an endocrine link between H. pylori-induced gastritis and duodenal ulcer. The aim of this study was to characterize cytokine effects on cultured rabbit antral G cells. METHODS: Monolayers (14.2% +/- 2.9% G cells) were studied after 48 hours in primary culture. RESULTS: Interleukin (IL) 1 beta (50% effective concentration [EC50], 5.3 +/- 0.4 ng/mL) and tumor necrosis factor (TNF) alpha (EC50, 5.5 +/- 0.5 ng/mL) stimulated gastrin release to 50% of the maximal response to 10(-9) mol/L neuromedin C. Stimulation by the maximally effective concentration of IL-1 beta (10 ng/mL) was inhibited by the human IL-1 receptor antagonist (100 ng/mL; inhibitory constant, 23.0 ng/mL), which prefers type I over type II IL-1 receptors. The response to the maximally effective concentration of TNF-alpha (10 ng/mL) was markedly inhibited by monoclonal antibody H398, an antagonist at TNF P55 receptors (inhibitory constant, 1.7 micrograms/mL), whereas monoclonal antibody utr1, an antagonist at TNF P75 receptors, was ineffective. Stimulation by IL-1 beta and TNF-alpha was additive to the responses to neuromedin C and O2-dibutyryl adenosine 3',5'-cyclic monophosphate. IL-6 and IL-8 (0.1-50 ng/mL) were ineffective. CONCLUSIONS: IL-1 beta and TNF-alpha stimulate gastrin secretion via receptors potentially residing on rabbit antral G cells themselves. We speculate that G cells express type I IL-1 receptors and TNF P55 but not TNF P75 receptors.

Animals↗
PubMed1994

Functional characterization of a muscarinic receptor stimulating gastrin release from rabbit antral G-cells in primary culture.

In previous studies carbachol-induced stimulation of gastrin release from antral G-cells in primary culture suggested the presence of muscarinic acetylcholine receptors on this cell type. Therefore, we attempted to pharmacologically characterize the muscarinic acetylcholine receptor subtype involved. Enzymatically isolated rabbit antral mucosal cells (0.8% G-cells) were separated by counterflow elutriation yielding a fraction (1.7% G-cells) that was placed in culture on collagen-coated well plates. After 24-36 h of culture 13.0 +/- 2.4% of total adherent cells were immunoreactive for gastrin as shown by immunocytochemical staining using the avidin-biotin complex method. In this preparation basal gastrin release ranged from 3.3 +/- 0.3 to 4.1 +/- 0.3% of total cellular content. Maximal gastrin release in response to the acetylcholine receptor agonist carbachol (10(-4) M) or the selective muscarinic receptor agonist arecaidine propargyl ester (10(-4) M) was 8.5 +/- 0.4% and 7.6 +/- 0.4% of total cellular content, respectively. The EC50 values were 3.7 +/- 0.5 x 10(-6) M carbachol and 1.8 +/- 0.4 x 10(-6) M arecaidine propargyl ester. At a concentration of 10(-6) M the non-selective muscarinic receptor antagonist atropine and the muscarinic M3 receptor preferring antagonist hexahydro-sila-difenidol (HHSiD; M3 > or = M1 > M2) completely inhibited gastrin release in response to carbachol (Ki values: 52 x 10(-9) M atropine and 29 x 10(-9) M HHSiD) and arecaidine propargyl ester (Ki values: 11 x 10(-9) M atropine and 13 x 10(-9) M HHSiD).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Type A and social support.

This investigation tested Matthews's hypothesis, which proposed that reduced social support may be one of the mediators of susceptibility to coronary disease in Type A individuals. In addition, sex differences were hypothesized to be an important aspect of the findings. Subjects were 72 women and 57 men undergraduate students who completed the Jenkins Activity Survey (JAS) and the Sarason Social Support Questionnaire. For women, both the Type A and Speed and Impatience subscales of the JAS were negatively related to satisfaction with social support. For men, however, Type A scores on JAS were positively correlated with satisfaction with social support. The implications of these findings, particularly with regard to the importance of separate analyses by sex, are discussed.

Adult↗
PubMedDate not supplied

Supplementation with dietary fiber improves fecal incontinence.

BACKGROUND: Human studies have shown that dietary fiber affects stool composition and consistency. Because fecal incontinence has been shown to be exacerbated by liquid stools or diarrhea, management strategies that make stool consistency less loose or liquid may be useful. OBJECTIVE: To compare the effects of a fiber supplement containing psyllium, gum arabic, or a placebo in community-living adults who were incontinent of loose or liquid stools. Mechanisms underlying these effects (e.g., fermentation of the fibers and water-holding capacity of stools) were examined. METHODS: Thirty-nine persons with fecal incontinence of loose or liquid stools prospectively recorded diet intake and stool characteristics and collected their stools for 8 days prior to and at the end of a 31-day fiber supplementation period. During the fiber supplementation period, they ingested psyllium, gum arabic, or a placebo by random assignment. RESULTS: In the baseline period, the groups were comparable on all variables measured. In the fiber supplementation period, (a) the proportion of incontinent stools of the groups ingesting the fiber supplements was less than half that of the group ingesting the placebo, (b) the placebo group had the greatest percentage of stools that were loose/unformed or liquid, and (c) the psyllium group had the highest water-holding capacity of water-insoluble solids and total water-holding capacity. The supplements of dietary fiber appeared to be completely fermented by the subjects as indicated by nonsignificant differences in total fiber, short chain fatty acids and pH in stools among the groups in the baseline or fiber supplementation periods. CONCLUSIONS: Supplementation with dietary fiber from psyllium or gum arabic was associated with a decrease in the percentage of incontinent stools and an improvement of stool consistency. Improvements in fecal incontinence or stool consistency did not appear to be related to unfermented dietary fiber.

Adult↗
PubMedDate not supplied

Oxyntomodulin: a cAMP-dependent stimulus of rat parietal cell function via the receptor for glucagon-like peptide-1 (7-36)NH2.

We have previously shown that in highly enriched rat gastric parietal cells the intestinal peptide hormones oxyntomodulin and glucagon-like peptide-2 (GLP-2) compete for receptor-binding with glucagon-like peptide-1 (GLP-1), a potent cAMP-dependent stimulus of H+ production in vitro. It is, however, unknown whether oxyntomodulin and GLP-2 elicit a biological response by interacting with the GLP-1 receptor. Therefore, we used enriched rat parietal cells to investigate the effects of both hormones on the production of cAMP and H+ ([14C]aminopyrine accumulation). Both parameters were stimulated by oxyntomodulin in a concentration-dependent manner. EC50 values were 6.2.10(-8) and 2.5.10(-7) M oxyntomodulin for stimulation of H+ and cAMP production, respectively. The maximally effective concentrations for stimulation of [14C]aminopyrine accumulation and cAMP production were 1.10(-6) and 1.10(-5) M oxyntomodulin, respectively. At these concentrations oxyntomodulin was nearly as effective as 10(-4) M histamine and equally effective as 10(-8) M GLP-1 (7-36)NH2. In the enriched parietal cell preparation there was no immunocytochemical evidence of contaminating D cells. Accordingly, the responses to oxyntomodulin and GLP-1 (7-36)NH2 were not augmented by incubating the cells in the presence of a polyclonal anti-somatostatin antibody. [14C]Aminopyrine accumulation in response to oxyntomodulin was inhibited by the GLP-1 (7-36)NH2 receptor antagonist, exendin (9-39)NH2, but not by the H2-receptor antagonist, ranitidine. Oxyntomodulin and carbachol acted additively to stimulate [14C]aminopyrine accumulation. GLP-2 (10(-7) to 10(-5)M) was without effect on basal H+ and cAMP production; however, at 10(-5) M GLP-2 markedly inhibited oxyntomodulin-stimulated [14C]aminopyrine accumulation. It is concluded that, by interacting with parietal cell receptors for GLP-1 (7-36)NH2, oxyntomodulin, but not GLP-2, directly stimulates H+ production by activating the adenylate cyclase.

Aminopyrine↗