Biomedical subjects

P A Epstein

Publications and source records attributed to P A Epstein.

6 recordsLinked to original sources

PubMed1989

Linkage studies on NIDDM and the insulin and insulin-receptor genes.

Twenty Black families in which at least two siblings had non-insulin-dependent diabetes mellitus (NIDDM) were typed for restriction-fragment-length polymorphisms at the insulin (INS), insulin-receptor (INSR), and HLA-DR beta loci. Evidence for linkage between NIDDM and these loci was assessed with various genetic models for the transmission of NIDDM and with the affected-sib-pair approach, which does not require assumptions concerning a genetic model for NIDDM. Tight linkage between NIDDM and any of the loci was unlikely under all of the genetic models examined. Similarly, for all three of the loci, the distribution of affected sib pairs sharing 2, 1, or 0 genes identical by descent was not significantly different from (and was very similar to) that expected if the locus were unrelated to disease susceptibility. There was no evidence for linkage heterogeneity for any of the loci when families were grouped according to obesity or age at onset or when considering families individually. We conclude that the INS and INSR loci can be ruled out as major susceptibility loci for NIDDM in most Black families segregating this disorder, but we recognize that defects at either of these loci may cause or contribute to NIDDM in some patients. In addition, it is possible that variation at the INS and/or INSR loci may contribute to NIDDM susceptibility by modifying susceptibility due primarily to another major gene(s) or as part of an overall polygenic component to NIDDM.

Black People↗

PubMed1987

Effect of an insulin-induced decrease in blood glucose on the human diabetic retinal circulation.

The effect of an insulin-induced decrease in blood glucose on the retinal blood flow (Q) was studied in 12 type II diabetics, using bidirectional laser Doppler velocimetry (BLDV) and monochromatic fundus photography. Q was first measured during hyperglycemia and then during normoglycemia which was achieved within approximately 3 hours by intravenous insulin administration. At normoglycemia, Q was 15% lower than at hyperglycemia (P less than 0.001). The decrease in Q was larger in patients with shorter disease duration. The authors also determined the regulatory change in Q during 100% oxygen breathing. Although this response remained subnormal, it was improved significantly in normoglycemia (P less than 0.01), particularly in those patients whose blood glucose level was decreased at a slower rate, suggesting that a gradual decrease in blood glucose may be beneficial.

Adult↗

PubMed1985

Modulation of intracellular Ca2+ in the parathyroid cell. Release of Ca2+ from non-mitochondrial pools by inositol trisphosphate.

Stimuli which enhance secretion from parathyroid cells such as low extracellular Ca2+ or Mg2+ are associated with a decrease in the cytosolic Ca2+ concentration as measured by quin2. Current evidence suggests that increased production of inositol 1,4,5-triphosphate (IP3) releases Ca2+ from cellular stores thus increasing cytosolic Ca2+. We used saponin-permeabilized dispersed bovine parathyroid cells to study the effect of IP3 on intracellular Ca2+. IP3 released Ca2+ from these cells in a dose-dependent manner; half-maximal response occurred with 0.3 microM IP3 and maximal response with 1.2 microM IP3. Permeabilized cells incubated in the presence of the mitochondrial inhibitor antimycin A released a similar amount of Ca2+ suggesting that IP3 releases Ca2+ from a non-mitochondrial pool. These results suggest that IP3 regulates cytosolic Ca2+ in this system and may function as a second messenger controlling hormone secretion.

Animals↗

PubMed1981

Dermo-distortive urticaria: an autosomal dominant dermatologic disorder.

A new hereditary physical urticaria, dermo-distortive urticaria (DDU), is described in a Christian Lebanese family. DDU is characterized by the appearance of pruritic, erythematosus, edematous, cutaneous swelling confined to the stimulated area in response to stimuli that vibrate or stretch the skin in a repetitive manner. The lesions appear within several minutes after stimulation and disappear within an hour. Extensive stimulation causes not only local urticaria but also a systemic response of faintness, headache, and facial erythema. Other than these annoying reactions, no other morbidity is associated with this disorder. While this disorder is certainly uncommon and its manifestations are more annoying than life threatening, it may be an important example of a heritable defect of inflammation control mechanisms. Although the mediator for the urticaria and systemic response was not isolated, a likely candidate is histamine. Computer analysis of the phenotype of 219 relatives in 6 generations shows that DDU is transmitted as an autosomal dominant trait with high penetrance. DDU is clinically distinct from hereditary angioneurotic edema, pressure urticaria, and dermographia. It is similar to vibratory angioedema (VA), but sufficient evidence to prove that DDU and VA are identical is not available.

Chromosome Aberrations↗

PubMed1981

Genetic linkage analysis of dermo-distortive urticaria.

We have described a new hereditary physical urticaria, dermo-distortive urticaria (DDU) [1]. In an attempt to man the locus of this autosomal-dominant disorder and to further characterize it, a linkage analysis with 18 genetic markers was done. Close linkage of DDU with TCII, GALT, Gc, Fy, Kell, and Se was excluded. The most significant positive lod score was for the MNSs blood antigen system, which has a maximum lod score of 1.09 at theta = 0.24 for all 28 family members who were typed. Although close linkage with DDU is not demonstrated at any marker, this study illustrates how linkage analysis may prove to be of value in the characterization of newly discovered heritable disorders.

Chromosome Aberrations↗

PubMed1980

Probable linkage between the human galactose-1-P uridyl transferase locus and 9qh.

Evaluation of a family in which electrophoretic variants of the eznyme galactose-1-phosphate uridyl transferase (GALT) and 9qh variants occur demonstrates close linkage between these two traits: lod score of 3.67 at theta = 0. Taken with information indicating GALT is on the short arm of chromosome 9, these linkage data suggest that this locus is close to the centromere on the short arm of chromosome 9.

Blood Protein Electrophoresis↗