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Biomedical subjects

J Simon

Publications and source records attributed to J Simon.

At least 307 records · Page 17Linked to original sources
PubMed1993

Corticosterone effect on insulin receptor number and kinase activity in chicken muscle and liver.

The effects of chronic corticosterone treatment (6 mg/kg/day) on insulin sensitivity and on liver and muscle insulin receptors were examined in 5-week-old chickens. The hypoglycemic effect of exogenous insulin was completely abolished within 2 weeks of treatment, suggesting a corticosterone-induced insulin resistance. Hepatic insulin receptor numbers were slightly reduced (P < 0.001) after 2 weeks of treatment. After 1 or 2 weeks, corticosterone treatment significantly reduced liver insulin receptor kinase activity toward the artificial substrate poly(Glu4,Tyr1). Muscle insulin receptor kinase activity was also significantly decreased after 1 week of treatment but this effect was accounted for by a decrease in basal activity. Therefore the corticosterone-induced insulin resistance is accounted for, at least in part, by altered hepatic receptor numbers and kinase activity. The impairment of muscle development involves postreceptor defects.

Adipose Tissue↗
PubMed1993

The kappa-opioid receptor: evidence for the different subtypes.

Classification of drugs acting on the kappa-opioid receptors seems to be difficult, since some of these ligands are also sigma agonists and/or display non-opioid actions as well. Furthermore, certain benzomorphans having kappa-agonistic character, are shown to be mu-antagonists too. Therefore the classification of the kappa-opioid receptor has to be presently restricted to two subclasses that also have physiological meaning. Dynorphin and Met-enkephalin-Arg6-Phe7 are proposed as endogenous peptide ligands for kappa-receptors. Nonpeptide agonists are benzeneacetamides interacting with the kappa1 receptor. Benzomorphans bind to both subtypes of kappa-receptors. No selective nonpeptide ligand for the kappa2 receptor exists as yet. Nor-binaltorphimine, a specific kappa-antagonist also inhibits both kappa-subtypes. Further research for kappa2 selective drugs is necessary for clear distinction between the two kappa-opioid binding sites. Molecular cloning of opioid receptors including their subtypes are expected to provide direct proof of their existence.

Animals↗
PubMed1993

cAMP and/or acetylcholine permit an insulin response to fuel nutrients in chicken.

1. The possibility that 8-bromo cyclic adenosine monophosphate (8-Br-cAMP) or acetylcholine (ACh) potentiates insulin release in chicken pancreas in response to D-glyceraldehyde (D-GA, a weak insulinotropic fuel), and permits an insulin release in response to D-mannose or alpha-ketoisocaproic acid (alpha-KIC) (two non-insulinotropic fuels in chicken pancreas) is examined. 2. 8-Br-cAMP (1 mM) or ACh (1 microM) permitted a sustained although delayed insulin release in response to D-GA (5 and 15 mM). 3. The resistance to D-mannose (50 mM) or alpha-KIC (10 mM) persisted in the presence of 8-Br-cAMP. 4. At 1 or 100 microM, ACh permitted a slight, immediate and transient insulin output in response to alpha-KIC but not to D-mannose (with one unexplained exception). 5. The simultaneous perfusion of 8-Br-cAMP + ACh increased the basal rate of insulin release, and permitted a large and sustained response to D-mannose. It also greatly increased the immediate response to alpha-KIC + ACh. 6. In conclusion, in chicken pancreas fuel nutrients require the activation of cAMP- and/or ACh-dependent pathways to induce insulin release. Whether this peculiarity is related to the high glycemia of chickens awaits further investigation.

3-O-Methylglucose↗
PubMed1993

Insulin receptor and insulin sensitivity in a chicken hepatoma cell line.

Insulin receptors have been characterized in a cell line recently isolated from a chicken hepatoma (LMH). The binding of 125I-insulin to LMH cells or membranes displayed the expected criteria for insulin receptors: affinity, temperature dependency, curvilinearity of Scatchard plot, rank order of potency for insulin analogs and insulin induced down-regulation. The alpha-subunit of LMH cell insulin receptors exhibited a normal size of 135 kDa. Following autophosphorylation, LMH WGA-purified receptors revealed a 95 kDa beta-subunit and a 72 kDa protein (pp72). Both proteins were phosphorylated in a time-, insulin- (and insulin-like growth factor 1; IGF-1) and manganese-dependent manner, and were precipitated by antiphosphotyrosine and two anti-insulin receptor antibodies. The 72 kDa protein was not present under non-reducing condition PAGE or in normal chicken liver. These results strongly suggest that pp72 is either a truncated form of the insulin receptor beta-subunit specific to LMH cells or a degradation product. Lectin-purified insulin receptors from LMH cells or chicken liver membranes exhibited similar tyrosine kinase activity, using artificial substrate poly(Glu-Tyr) 4:1. Finally, amino acid uptake by LMH cells was insulin stimulatable.

Amino Acid Sequence↗
PubMed1993

Unsuspected varicella-zoster virus encephalitis in a child with acquired immunodeficiency syndrome.

We report a case of progressive encephalitis caused by varicella-zoster virus (VZV) in an adolescent with hemophilia and acquired immunodeficiency syndrome but without cutaneous signs of VZV infection. Magnetic resonance imaging of the brain demonstrated an abnormally increased periventricular signal in T2-weighted images. Infection with VZV was proved by in situ hybridization and immunofluorescence staining of brain tissue, which showed histologic evidence of herpesvirus infection. Encephalitis caused by infection with VZV is a potentially treatable complication of acquired immunodeficiency syndrome and requires a high index of suspicion for diagnosis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Progesterone antagonist RU 486 accommodates but does not induce labour and delivery in primates.

The hormonal mechanisms of parturition in primates remain controversial. Even so, the well-known decrease of plasma progesterone concentration near term is considered by many as the 'labour inducer'. The progesterone antagonist RU 486, which blocks progesterone activity at the cellular receptor level, appears to be a useful hormonal tool by which to study this tissue. Here, we tested its capacity to induce labour and delivery. A total of 23 Cynomolgus monkeys (Macaca fascicularis), within 9-17 days of expected term, were assigned to four different protocols to study various doses, routes and regimens of RU 486 administration. Observations included uterine contractile patterns, pharmacokinetics of RU 486 in plasma and passage of RU 486 into breast milk. None of the protocols tested successfully induced labour resulting in vaginal delivery within 24 h. Instead, the data demonstrate that blockade of progesterone activity by the progesterone antagonist was not sufficient by itself to achieve parturition in these primates. Uterine myometrial contractile activity under RU 486 exposure was not sufficient to induce labour and delivery. Moreover, the progesterone antagonist concentration in breast milk was very low, indicating little passage to suckling newborn infants.

Animals↗
PubMed1993

The etiology of autism: pre-, peri- and neonatal factors.

OBJECTIVE: To examine pre-, peri-, and neonatal factors in autism using composite optimality scores. METHOD: Pre-, peri-, and neonatal composite optimality scores were examined in 39 autistic subjects and 39 randomly matched sibling controls using a modification of the Gillberg Optimality Scale (Modified-GOS). Scores were based on best-estimate ratings of maternal interviews and medical records. Rules for best-estimate ratings were derived from a study of agreement between these two sources. RESULTS: Significant differences in optimality between autistic probands and their siblings were not present after adjustment for "maternal parity." Examination of specific variables revealed that only maternal parity differed significantly between autistic subjects and randomly matched sibling controls, reflecting an excess of first and fourth born among the autistic subjects. CONCLUSION: The findings of this study suggest that previous reports of an association between optimality and autism are a result of failure to adjust for birth order.

Adolescent↗
PubMed1993

Insulin resistance in the GK rat: decreased receptor number but normal kinase activity in liver.

We have previously shown that the glucose intolerance and the hyperglycemic state in the GK rat, a new spontaneous model of non-insulin-dependent (type II) diabetes without obesity, are partly accounted for by an alteration of the pancreatic B cell response. On the other hand, the hyperglycemic-hyperinsulinemic pattern in these rats suggests a decrease of response to insulin in the basal state. In the present study, in vivo insulin action was assessed in 8-wk-old GK females at basal and submaximal (euglycemic clamp) insulin levels. Overall glucose utilization (OGU), individual tissue glucose utilization (ITGU, in vivo uptake of the glucose analogue 2-deoxy-D-glucose as the relative index of glucose metabolism), as well as hepatic glucose production (GP) and liver insulin receptor properties were determined under these two conditions. The basal OGU was significantly higher in the GK females, compared with that in control Wistar females. The hyperinsulinemic-euglycemic clamp experiments indicated that peripheral insulin resistance was installed at 8 wk of age in the GK females because 1) OGU was significantly lower and 2) in some peripheral tissues (epitrochlearis muscle, periovarian, and inguinal white adipose tissues), but not all, ITGU was significantly lower compared with corresponding ITGU in control rats. In the basal state GP was significantly higher in the GK rats. At submaximal hyperinsulinemia (and euglycemia), it was less effectively suppressed than in the controls, thus demonstrating liver insulin resistance. Under both basal state and clamp condition, binding of 125I-A14-insulin to liver membranes of GK rats was significantly decreased by 20-30%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Insulin-like growth factor-I-stimulated glucose transport in myotubes derived from chicken muscle satellite cells.

The effects of insulin and insulin-like growth factor-I (IGF-I) on glucose transport were compared in myotubes derived from chicken breast muscle satellite cells in vitro. Myotubes were incubated (for 0.5 or 4 h) with or without glucose in the presence or absence of insulin or IGF-I. Glucose uptake was subsequently measured by the incorporation of 2-[1,2-3H(N)] deoxy-D-glucose ([3H]2DG) in glucose-free medium (10 min at 20 degrees C). Glucose uptake was almost completely abolished by the addition of cytochalasin B or phloretin. It was increased by a decrease in glucose concentration in the incubation medium. Insulin (5 mg/l) stimulated [3H]2DG uptake to a maximum of 43 +/- 10% above basal after 30-min incubation and 101 +/- 15% after 4-h incubation. IGF-I and insulin at equimolar concentrations (25 micrograms/l and 20 micrograms/l respectively) were almost equipotent after 0.5 h but after 4-h incubation IGF-I was 17-fold more potent, suggesting that this 'late' effect was mediated through the IGF-I receptor. Incubation with cycloheximide suggested that the effect of IGF-I involved increased protein synthesis. The results suggest that chicken myotubes express a glucose transporter which is regulated by IGF-I and glucose concentration. However, they do not appear to express a typical insulin-responsive transport system.

Animals↗
PubMed1993

[Significance of the stress score in patients with coronary artery disease].

The authors tested the importance of the load score for assessment of the prognosis of patients after myocardial infarction and for assessment of the severity of the atherosclerotic affection of the coronary arteries. The score is a numerical value calculated from data assembled during evaluation of bicycle ergometry according to the following formula: total duration of the load-(5X deviation of ST)-(4X anginous index). The value of the load score was retrospectively tested in a group of 31 patients after myocardial infarction (mean age 58.1 years), who died during the subsequent five years, and in 64 subjects, mean age 50.1 years, who were subjected to coronarography. The value of the load score in 77.4% of the group who died was less than -10. In the group of patients subjected to coronarography where three arteries or the trunk of the left coronary artery was affected the score in 81.8% of the patients was smaller than -10. The authors proved a close correlation between the value of the load score and the severity of affection of the coronary arteries. Therefore the load score can be used as one of the factors when selecting patients for coronarographic examination and revascularization of the heart muscle. The lead score helps also in the estimation of the prognosis after myocardial infarction.

Coronary Vessels↗
PubMed1993

[Preventive cardiology in the Czech Republic. Present status and perspectives].

Despite their proclaimed goals, prevention campaigns were little effective in the past. Now it is time to discard those highly publicized programmes. Preventive cardiology can be successful in reducing the incidence and mortality only on condition the endeavor of the public health system is combined with a well functioning service of general practitioners and family physicians. The nationwide model of prevention should be translated into practice by institutes of public health and hygiene and should improve, mainly by redefining the dietary habits and smoking cessation programmes, the risk profile of the entire population. It should be remembered that even a minor change in the risk profile in the whole population has society-wide implications and entails a significant decrease in the number of clinically manifest cases of the disease. While secondary prevention after myocardial infarction will continue to be the responsibility of the cardiologist, individualized intervention in persons at high risk, as part of primary prevention, can be provided generally only on condition it is performed by the general practitioner and the family physician. All multi-level models designed to refer patients and persons at risk step by step, according to the degree of risk, up the health system, as proposed by socialist health care, are not practicable. Today, the general practitioner can consult the expert directly should the need arise. Successful prevention will depend on the standard and education of the general practitioner on the one hand, and the performance of public health institutions on the other.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular Diseases↗
PubMed1992

Solubilization and molecular size determination of the P2x purinoceptor from rat vas deferens.

Membranes of the rat vas deferens were shown to contain a high density of binding sites for [3H] alpha, beta-methylene ATP ([3H] alpha, beta-MeATP), a ligand selective for the P2X purinoceptor. Analysis demonstrated two classes, of high affinity (Kd = 1.8 nM, Bmax (maximum density) = 9.3 pmol/mg of protein) and of low affinity (Kd = 34 nM, Bmax = 29 pmol/mg of protein). The high affinity [3H] alpha, beta-MeATP binding sites were successfully solubilized with 2% digitonin: the Kd was then 1.6 nM. Both the association and dissociation of the receptor-ligand complex were rapid (half-time for association = 6.5 min). The rank order of potency of purinergic ligands in displacing [3H] alpha, beta-MeATP binding from the solubilized preparation was in accord with the pharmacological criteria for P2X purinoceptors. The receptor-detergent complex was separated by sucrose gradient ultracentrifugation from the ATPase enzymes also present in the preparation. The sedimentation coefficient of the receptor-detergent complex was 12.1 S. It was shown that [3H] alpha, beta-MeATP can function as a photoaffinity labeling reagent upon exposure to ultraviolet light; in the rat vas deferens membranes, it thus became cross-linked in a specific manner to a polypeptide of apparent molecular mass = 62,000 daltons, proposed to be the ligand-binding subunit of the functional P2X purinoceptor.

Adenosine Triphosphatases↗
PubMed1992

Exercise tolerance in panic disorder patients.

Sixteen panic patients and fifteen normal controls performed submaximal exercise testing on a bicycle ergometer. Only one patient subject panicked. Biochemical, physiological, and psychological data showed similar exercise tolerance in both patients and controls. Exercise-induced distress and lactate increment do not appear to cause panic attacks.

Adult↗
PubMed1992

[Insulin in type 2 diabetes. Why, when, how?].

Non insulin-dependent diabetes is often associated with obesity and always with some degree of insulin resistance. First choice treatment consists of appropriate and sometimes hypocaloric diet and oral hypoglycemic agents. Using insulin becomes mandatory in patients with associated pathology or at risk of metabolic imbalance. Insulin administration must be discussed in each individual case when it aims at a long-term improvement of blood glucose control, taking into account the lack of consensus on this point and the potential drawbacks of insulin therapy, notably weight increase and risk of hypoglycaemia.

Diabetes Mellitus, Type 2↗
PubMed1992

Protection by opioid ligands against modification of the opioid receptor by a carbodiimide.

Opioid receptors in membranes prepared from guinea-pig cerebellum were modified irreversibly by treatment with a water soluble carbodiimide, 1-ethyl,3-(3-dimethylaminoethyl)carbodiimide (EDAC). This decreased the number of [3H]bremazocine binding sites (Bmax reduced from 140 to 100 fmol/mg by 1 mM EDAC) without changing their affinity. When the EDAC concentration used was sufficient (500 mM) to inactivate almost all of the opioid receptors, the modification was partly prevented by inclusion of high concentrations (100 microM) of opioid agonists ([D-Ala2, MePhe4, Glyol5]-enkephalin, [D-Ala2, D-Leu5]-enkephalin,(+)-trans-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzo(b)thiophene-4-acetamide hydrochloride), although they exhibited equal efficacy irrespective of their mu, delta or kappa type selectivity. However, almost all of the opioid binding sites were protected when a guanine nucleotide analogue (GppNHP, 100 microM) was also included with the agonists during carbodiimide treatment.

Animals↗