Glycogen synthase: a putative locus for diet-induced hyperglycemia.

Inbred mouse strains fed a diabetogenic diet have different propensities to develop features analogous to type 2 diabetes mellitus. To define chromosomal locations that control these characteristics, recombinant inbred strains from diabetes-prone C57BL/6J (B/6J) and diabetes-resistant A/J strains were studied. Insulin levels and hyperglycemia correlated with two different regions of mouse chromosome 7 (two point LOD scores > 3.0). For insulin levels, 15 of 16 recombinant inbred strains were concordant with a region that contains the tubby mutation that results in hyperinsulinemia. For hyperglycemia, 19 of 23 strains were concordant with the D7Mit25 marker and 20 of 23 strains with the Gpi-1 locus on proximal mouse chromosome 7. Using more stringent criteria for hyperglycemia, 10 of 11 strains characterized as A/J or B/6J like were concordant with D7Mit25. This putative susceptibility locus is consistent with that of the glycogen synthase gene (Gys) recently suggested as a candidate locus by analyses of type 2 diabetes patients. Fractional glycogen synthase activity in isolated muscle was significantly lower in normal B/6J diabetic-prone mice compared with normal diabetic-resistant A/J mice, a finding similar to that reported in relatives of human patients with type 2 diabetes. These data, taken together, raise the possibility that defects in the Gys gene may in part be responsible for the propensity to develop type 2 diabetes.     

CIRCULATING ANTIDIURETIC HORMONE DURING LABOUR AND IN THE NEWBORN

Abstract. Leung, A., McArthur, R., McMillan, D., Ko, D., Deacon, J., Parboosingh, J. and Lederis K. (the Divisions of Paediatrics, Pharmacology and Obstetrics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada). Circulating antidiuretic hormone during labour and in the newborn. Acta Paediatr Scand, 69: 505, 1980.—Using a high specificity radioimmunoassay, antidiuretic hormone (ADH) concentrations were measured in the plasma of 33 expectant mothers during labour, in cord arterial and venous plasma of their infants at the time of delivery (19 delivered vaginally; 14 delivered by Cesarean section) and in the plasma of the same infants in the first few days of life. Extremely high concentrations of ADH (about 50 times higher than adult basal concentrations) were present in cord arterial blood indicating active fetal production of ADH. Plasma ADH decreased rapidly within an hour after birth and usually fell to adult basal levels during the first day of life. Stressed babies and babies subjected to difficult deliveries had higher plasma levels of ADH.     

Atrioventricular Dissociation During Paroxysmal Junctional Tachycardia

We describe the rare occurrence of atrioventriculor dissociation in three patients during paroxysmal functional tachycardia. The mechanism of tachycardia was atrioventricular nodal reentry in two patients. The third patient had reentrant tachycardia that utilized the A V node for at least part of the reentrant circuit. This patient also had a nodoventricular pathway that may have participated in the reentrant circuit. In two patients, ventricular tachycardia was diagnosed prior to electrophysiologic assessment and medication to prevent tachycardia was not successful. After electrophysiological studies, treatment directed at suppressing AV nodel reentry prevented recurrent tachycardia. These case studies demonstrate the importance of detailed electrophysiological assessment of tachycardia in patients whose arrhythmia does not respond to empirical antiarrhythmic therapy. (PACE, Vol. 4, November-December, 1981)     

Mechanism of the Anemia of Pyridoxine Deficiency in the Rat

Rats were fed a diet deficient in pyridoxine until they developed a microcytic, hypochromic, pyridoxine-responsive anemia. Studies of red cell survivaltime demonstrated that there was a hemolytic factor involved in this anemia;and the more severe the anemia, the more rapid the destruction of red cells.It also demonstrated that the defect was intracorpuscular. Blood regenerationstudies confirmed findings by others that erythropoiesis was impaired in pyridoxine deficiency, particularly when the accompanying anemia was severe.These studies indicate that a dual mechanism may be operating in theseanemic rats.

Submitted on February 15, 1967 Accepted on April 17, 1967     

Clinimetrics in parkinsonism]

Clinimetrics, which has been developed beginning from stroke scales, nowadays is used in evaluation of many other diseases. It is needed as well for evaluation of impairment and functional state as for clinical assessment of new drugs. Lately one can observe shifting of attention to psychosocial issues. In this paper the most commonly used scales for evaluation of impairment, activities in daily living and quality of life in parkinsonism have been critically presented. Those scales are reliable and valid in the assessment of treatment, prognosis, classification of invalidity and social care decisions.     

New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch

Severe hypoxia caused by a lack of vascular supply and an inability to retrieve encapsulated islets transplanted in the peritoneal cavity for biopsy and subsequent evaluation are obstacles to clinical application of encapsulation strategies for islet transplantation. We recently proposed an omentum pouch model as an alternative site of encapsulated islet transplantation and have also described a multi-layer microcapsule system suitable for coencapsulation of islets with angiogenic protein in which the latter could be encapsulated in an external layer to induce vascularization of the encapsulated islet graft. The purpose of the present study was to determine the angiogenic efficacy of fibroblast growth factor (FGF-1) released from the external layer of the new capsule system in the omentum pouch graft. We prepared 2 groups of alginate microspheres, each measuring ∼600 μm in diameter with a semipermeable poly-L-ornithine (PLO) membrane separating 2 alginate layers. While one group of microcapsules contained no protein (control), FGF-1 (1.794 μg/100 microcapsules) was encapsulated in the external layer of the other (test) group. From each of the 2 groups, 100 microcapsules were transplanted separately in an omentum pouch created in each normal Lewis rat and were retrieved after 14 days for analysis of vessel density using the technique of serial sample sections stained for CD31 with quantitative three-dimensional imaging. We found that FGF-1 released from the external layer of the test microcapsules induced a mean ± SD vessel density (mm²) of 198.8 ± 59.2 compared with a density of 128.9 ± 10.9 in pouches measured in control capsule implants (P = .03; n = 5 animals/group). We concluded that the external layer of our new alginate microcapsule system is an effective drug delivery device for enhancement of graft neovascularization in a retrievable omentum pouch.