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M Mark

Publications and source records attributed to M Mark.

140 records · Page 8Linked to original sources
PubMed1987

Effects of propylthiouracil and methylthiouracil on cyclic AMP and ion movements in rat pancreatic islets.

Propylthiouracil and methylthiouracil have been shown to potentiate glucose-induced insulin secretion from rat pancreatic islets: the effect of methylthiouracil being less pronounced than that of propylthiouracil. In this study the effects of these substances on cAMP levels, 86Rb+ efflux, 45Ca2+ net uptake, and 45Ca2+ efflux were tested in isolated rat islets in order to obtain information on their possible mechanism of action. Propylthiouracil and to a lesser extent methylthiouracil increased islet cyclic AMP in a concentration-related manner. Maximum increases at the highest concentrations tested were 261% and 190% respectively. In the presence of 3 mM glucose propylthiouracil and methylthiouracil led to a decrease in the 86Rb efflux rate. With 5.6 mM glucose, both thiourea derivatives produced an increase in the 86Rb+ efflux rate which was independent of the presence or absence of calcium in the medium. Propylthiouracil and methylthiouracil augmented the 45Ca2+ efflux rate in the presence as well as in the absence of external calcium at various glucose concentrations. Propylthiouracil did not change, and methylthiouracil only slightly augmented, 45Ca2+ net uptake into the isolated islets. It is suggested that the synergistic effect of propylthiouracil and methylthiouracil on glucose-induced insulin release is at least in part due to an increase in islet cAMP levels. Whether the two substances have additional direct effects on ionic fluxes which contribute to their insulinotropic action or whether the observed changes in ion movements are secondary to the elevation of cAMP levels remains to be unclear and needs further investigation.

Animals↗
PubMed1987

Significance of Ca2+, Rb+ fluxes, of cAMP and cGMP for the CCK8-modulated insulin release.

In rat pancreatic islets the effects of cholecystokinin-8 (CCK8) on glucose-mediated insulin release, 45Ca2+ net uptake, 45Ca2+ efflux, 86Rb+ efflux, cAMP- and cGMP levels were studied. In the presence of a substimulatory glucose concentration (3 mM) CCK8 concentrations of up to 1 microM had no effect on insulin release, but CCK8 at 10 nM potentiated the stimulatory effect of glucose (11.1 mM). 10 nM CCK8 enhanced glucose-stimulated 45Ca2+ net uptake but was ineffective at substimulatory glucose levels. CCK8 had no effect on cAMP and cGMP levels in the presence of 11.1 mM glucose, CCK8 increased 86Rb+ (a measure of K+) in the presence of both 3 and 11.1 mM glucose. This effect was abolished when Ca2+ was omitted from the perifusion medium. CCK8 did not alter glucose (11.1 mM)-stimulated 45Ca2+ efflux rate. These data indicate that (1) CCK8 potentiates glucose-stimulated insulin secretion possibly via an effect on Ca2+ uptake, 2) by affecting Ca2+ uptake, CCK8 enhances K+ efflux, and 3) CCK8 does not mediate its effect via cAMP or cGMP. With respect to 86Rb+ efflux the mechanism of CCK8 action appears to be different from that of glucose. When the mechanism of CCK action on islets is compared with that on exocrine pancreas (data from others) there are similarities (importance of Ca2+ uptake and non-importance of cAMP and cGMP).

Animals↗
PubMed1987

The effect of glucose on insulin release and ion movements in isolated pancreatic islets of rats in old age.

1. The effect of glucose on 86Rb+ efflux, 45Ca2+ net uptake and insulin secretion of pancreatic islets from 3- and 24-month-old rats was studied. 2. Raising the glucose concentration from 3 to 5.6 and 16.7 mM had no effect on 86Rb+ efflux from islets of 24-month-old male rats whereas that from 24-month-old female rats was decreased. 3. At 16.7 mM-glucose, net uptake of 45Ca2+ was significantly diminished in islets of 24-month-old rats compared to islets of 3-month-old rats. 4. In the presence of 16.7 mM-glucose, islets of 24-month-old rats exhibited only 60-70% of the insulin release obtained with islets from 3-month-old rats. 5. Neither net uptake of 45Ca2+ nor insulin secretion appear to differ between the sexes. 6. These data suggest that the decreased insulin secretory response to glucose during old age is due, at least in part, to inadequate inhibition of K+ efflux and diminished net uptake of Ca2+.

Aging↗
PubMed1985

Thiols and pancreatic beta-cell function: a review.

In pancreatic islets insulin secretion in response to a variety of stimulators is sensitive to the redox state of extracellular and intracellular thiols. In this connection variations of plasma glutathione (GSH) may also be of importance. In the process of stimulus-secretion coupling, membrane thiols play an important role. One major localization of critical thiols appears to be related to the influx of calcium through the voltage-dependent channel. Other transmembranal ion movements and the cAMP system seem to be less sensitive to thiol oxidation than calcium influx via voltage-dependent Ca channels.

Adenylyl Cyclases↗
PubMed1985

Dental cell interaction with extracellular-matrix constituents: type-I collagen and fibronectin.

It has been suggested that, during odontoblast differentiation, the extracellular matrix present at the epitheliomesenchymal junction modulates the activity of the cytoskeleton by means of membrane constituents (proteins, proteoglycans or gangliosides). To investigate this, we studied the interaction of iodinated fibronectin and type-I collagen with dissociated dental tissues and with membrane proteins prepared from these tissues. Isolated dental papillae and enamel organs were cultured for increasing periods of time in the presence of iodinated proteins. Fibronectin and type-I collagen were preferentially bound to dental papillae; however, after 6 h of incubation, fibronectin no longer interacted with the dental papillae, and the bound radioactivity was released. In the meantime, de novo synthesized fibronectin was deposited in the extracellular matrix of the dental papillae. Membrane proteins were prepared from isolated enamel organs and dental papillae. After sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, these proteins were transferred to nitrocellulose by electroblotting and then incubated in the presence of either 125I-labelled fibronectin or 125I-labelled type-I collagen. Autoradiography confirmed the preferential interaction of fibronectin with the dental papilla. Fibronectin interacted with three high-molecular-weight proteins (Mr, 145,000, 154,000 and 185,000), which were not detected when membranes were prepared from enamel organs. Under the same conditions, type-I collagen did not interact with membrane proteins. The known interaction of type-I collagen with the plasma membrane of dental-papilla cells might be mediated either by another constituent of the extracellular matrix or by cell-surface-associated proteoglycans.

Animals↗
PubMed1985

Failure of glucose to affect 86rubidium efflux and 45calcium uptake of fetal rat pancreatic islets.

Ion movements and insulin secretion of pancreatic islets of adult and fetal rats have been studied at three glucose concentrations. In islets of adult rats, 86Rb efflux is maximally decreased by 5.6 mM-glucose. 16.7 mM-glucose caused a biphasic efflux pattern which may be due to glucose-stimulated Ca uptake. In islets of fetal rats elevation of the glucose concentration from 3 to 5.6 or 16.7 mM does not cause a change of 86Rb efflux, and the fractional efflux from fetal islets in the presence of 3 mM-glucose is similar to that from adult rat islets in the presence of 5.6 mM-glucose. Elevation of the glucose concentration from 3 to 16.7 mM is not associated with an increase in 45Ca uptake into fetal islets, although this change in glucose concentration doubles 45Ca uptake into adult islets. When challenged with 16.7 mM-glucose, fetal islets exhibit no insulin secretory response; however, they do respond to theophylline. It is concluded that the failure of fetal islets to exhibit an insulin-secretory response when challenged with glucose might be related to the inability of glucose to affect 86Rb efflux and Ca uptake. The present data are discussed in light of differences between pancreatic islets of fetal and adult rats with respect to the redox state of pyridine nucleotides, thiols and glucose metabolism.

Animals↗
PubMed1975

A central nervous system depressant-antidepressant.

A new tricyclic agent with an allenyl side chain experimentally shows antidepressant activity similar to amitriptyline and imipramine but also exerts marked CNS depression. Such dual activity should be of clinical interest for treatment of mixed anxiety and depression.

Alkadienes↗
PubMedDate not supplied

Changes in diagnosis in a 9-year national longitudinal sample.

Studied are changes in diagnosis in a random sample of 10% of all first admissions to psychiatric hospitals and psychiatric wards of general hospitals in Israel from 1983 to 1990 with follow-up evaluation to 1991. This included 4,570 hospitalizations of 2,220 patients. Data were extracted from the National Psychiatric Case Registry of the Ministry of Health. Almost 59% of the sample had one admission, 18% had two, 9% had three, and 14% had four or more. From the first admission to the last discharge (a mean of 2.15 years), 59.2% of the patients' diagnoses did not change. In 89.46% of the cases in which the diagnosis changed, the changes took place during the first admission. Diagnostic change differed between diagnostic groups. In descending order of stability in diagnosis from the first admission to the last discharge were neurotic and personality disorder (73.6%), mental retardation (73.5%), schizophrenia (73.0%), organic conditions (70.6%), affective disorders (66.2%), substance abuse (65.6%), childhood disorders (60%), paranoid disorder (43.6%), other nonorganic psychosis (30.3%), and V-codes (25.0%). The average level of diagnostic agreement between the first admission and the last discharge was a kappa of .52. The average length of stay for patients whose diagnosis became more severe was considerably longer than for patients whose diagnosis became less severe or did not change in level of severity. Older age was related to less change in diagnosis. For patients aged less than 18 years, diagnosis changed in 46.7% of the cases, for patients aged 19 to 44, 31.2%, and for patients older than 45, 27.8%.

Adolescent↗
PubMedDate not supplied

How individual clinicians make admission decisions in psychiatric emergency rooms.

The goal of this study was to understand how individual clinicians make admission decisions in the psychiatric emergency room. Clinical and demographic data were collected on 7485 consecutive visits to four psychiatric hospitals in Israel during 1991 and 1992. This was about one-third of visits to psychiatric emergency rooms in Israel during this time. Twenty-one decision makers who made at least 50 decisions and admitted more than 15 and less than 85% of patients were included. Decision to admit patients was modeled using step-wise discriminant analysis. Clinicians examined different numbers of patients and admitted at different rates. In one hospital one group of clinicians appears to rely primarily on diagnosis and another group on other variables, predominately previous history, and social or referral factors. The most influential background variable was self-referral which favored not admitting patient. The most influential diagnoses were schizophrenia and affective disorder which favored admission. In another hospital the most important variables in most models were legal status of admission, number of previous hospitalizations, violence and suicide as presenting problems and referral source. All variables except referral source favored admission. Some referral sources favored admission and others did not. In the last hospital studied the most salient variable was self-referral which favored not admitting patient. Decisions in one hospital were not modeled because no clinician met study inclusion criteria. There appears to be variability between clinicians in what information they use to make their decisions in the psychiatric emergency room and what percent of patients they admit.

Decision Making↗
PubMedDate not supplied

Immunological analysis of enhanced spontaneous metastasis in WKA rats following cryosurgery.

We have previously reported that inhibition of anti-tumor immune responses and enhancement of metastatic tumor growth occurred in rats following cryosurgery of the transplantable 3-methlcholanthrene-induced rat fibrosarcoma KMT-17. In this study, to elucidate the immunological responses in rats following cryosurgery, we examined whether rat serum obtained from rats which underwent cryosurgery (c-serum) might affect the in vivo neutralizing activity of the Winn assay. In this assay, c-serum did not reduce the anti-tumor immunity, though spleen cells obtained from rats undergoing surgical excision indicated strong anti-tumor immunity as compared with cryosurgery. Thus, we examined the anti-tumor responses of spleen cells. Macrophages were obtained from the glass adherent fraction of rat spleen cells following cryosurgery and these macrophages were used for cytostatic activity against KMT-17 cells. Cytostatic activity was not reduced by cryosurgery. The spleen cells obtained from rats receiving cryosurgery were intravenously transferred into other rats that were previously immunized with 80 Gy-irradiated KMT-17 cells, and an alteration of tumor growth modulated by this adoptive cell transfusion was observed. The anti-tumor resistance of rats was diminished by the adoptive transfusion of spleen cells treated with cryosurgery, though this diminution disappeared following anti-T serum and immune complement treatment of spleen cells. These results suggest that immuno-suppression following cryosurgery may be mainly caused by suppressor T cells.

Adoptive Transfer↗