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P Sehgal

Publications and source records attributed to P Sehgal.

15 recordsLinked to original sources
PubMed1992

Persistence of impaired insulin secretion in infant rhesus monkeys that had been hyperinsulinemic in utero.

Chronic in utero hyperinsulinemia in the fetal rhesus monkey produces a number of changes in the fetus that are similar to those found in the human infant of the diabetic mother, including macrosomia, selective organomegaly, and altered insulin secretion during the neonatal period. The chronically hyperinsulinemic fetal rhesus model has been used to test the hypothesis that the effects of chronic hyperinsulinemia persist beyond the neonatal period into later life and may, in part, be responsible for the increased prevalence of impaired glucose tolerance or diabetes found in the human infant of the diabetic mother. We report that infant rhesus monkeys that had plasma insulin concentrations of approximately 10 times basal levels (2176 +/- 808 pmol compared to 172 +/- 101 pmol) exhibited reduced insulin secretion during the first 5 months of life. The integrated incremental change in plasma insulin and immunoreactive C-peptide (IRCP) concentration was significantly reduced by approximately 50% in response to i.v. glucose, arginine, and tolbutamide when given at 3, 4, and 5 months of age. The response to glucagon at 2 months of age was equivocal with a significantly reduced insulin response but without the corresponding IRCP reduction. There was no difference between groups in insulin sensitivity as measured at 6 months of age by an i.v. insulin tolerance test. The glucagon and glucose tolerance tests were repeated annually in both groups until the animals were 3 yr of age with no differences in insulin or IRCP secretion being observed. We conclude that chronic in utero euglycemic hyperinsulinemia results in impaired insulin secretion that persists beyond the neonatal period.

Animals↗
PubMed1992

Impaired insulin secretion after intravenous glucose in neonatal rhesus monkeys that had been chronically hyperinsulinemic in utero.

Chronic hyperinsulinemia in the fetal rhesus monkey results in fetal macrosomia without change in fetal plasma glucose concentration. After 18 days of hyperinsulinemia, fetuses were delivered by cesarean section, at which time experimental animals had significantly (P less than 0.05) elevated umbilical artery plasma insulin concentrations of 2039 +/- 854 pM compared with 129 +/- 72 pM. Plasma immunoreactive C peptide (IRCP) was significantly reduced to 39 +/- 17 pM compared with 286 +/- 134 pM. Eight hours after the insulin-delivering pumps were removed, plasma glucose, insulin, and IRCP were the same in both the experimental and control groups. At this time, 0.5 g glucose/kg was given intravenously and insulin and IRCP secretion was measured over a 1-hr period. The secretion, as assessed by integrating the incremental response of both insulin and IRCP, was significantly (P less than 0.05) lower by 80% in the experimental animals compared with the controls. Our data show that experimentally produced in utero euglycemic hyperinsulinemia in the fetal rhesus monkey produces a defect in the glucose-mediated insulin secretory mechanism that is detectable in the neonatal period even when hyperinsulinemia is no longer present. This study provides more support for the concept that fuel/hormone-mediated fetal teratogenesis may explain some of the fetopathy of the infant of the diabetic mother.

Animals↗
PubMed1991

Patterns of erythropoiesis and anaemia in leprosy.

A total of 128 leprosy patients were investigated for the morphological type of anaemia, the underlying disturbances in iron metabolism and patterns of erythropoiesis and other cytomorphological changes in the bone marrow. The anaemia was a mild to moderate degree in paucibacillary (PB) leprosy, while in multibacillary (MB) leprosy it was of a severe degree. Iron deficiency was observed in only a few patients. Impaired iron utilization as observed in a anaemia of a chronic disorder was a common finding in MB leprosy (41.7%) and more so in new cases (50%). Megaloblastic erythropoiesis was also more frequent in MB leprosy (45.2%) as compared to PB leprosy (16%), accounting for the severe degree of anaemia in the former type. In 17.2% of the total patients (MB, 21.4%; PB, 9%) both megaloblastic erythropoiesis and features of impaired iron utilization were observed in bone marrow. Disturbances in iron metabolism and erythropoiesis were also observed but to a lesser degree in patients receiving specific antileprosy treatment. Irrespective of the type of disease and duration of treatment, increasing frequency of acid-fast bacillia (AFB) positivity and granulomas was observed in the bone marrow with an increasing severity of anaemia.

Anemia↗
PubMed1990

Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus.

Better understanding of the pathogenesis of acquired immunodeficiency syndrome (AIDS) would be greatly facilitated by a relevant animal model that uses molecularly cloned virus of defined sequence to induce the disease. Such a system would also be of great value for AIDS vaccine research. An infectious molecular clone of simian immunodeficiency virus (SIV) was identified that induces AIDS in common rhesus monkeys in a time frame suitable for laboratory investigation. These results provide another strong link in the chain of evidence for the viral etiology of AIDS. More importantly, they define a system for molecular dissection of the determinants of AIDS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Impaired insulin secretion in the neonatal rhesus monkey after chronic hyperinsulinemia in utero.

The secretion of insulin by the pancreas of the newborn rhesus monkey that had been made experimentally hyperinsulinemic in utero was studied in 18 animals. Chronic in utero hyperinsulinemia was produced by the continuous subcutaneous delivery of 4.75 units of insulin per day for 18 +/- 1 days. After delivery, the insulin-containing pump was removed to allow neonatal insulin levels to drop to normal levels. By 6.5 +/- 1.0 hr after pump removal, plasma glucose, insulin, and C-peptide immunoreactivity (CPIR) were comparable in the control and experimental animals. At that point 300 micrograms of glucagon/kg body weight was given iv to stimulate insulin secretion. After 30 min a significant elevation (expressed as the percentage of basal levels) in plasma glucose by 250%, insulin by 200%, and CPIR by 200% was observed in the control animals. In contrast, no changes in plasma insulin or CPIR concentrations occurred, with an attenuated glucose response that was only one-fifth of the control response, in the experimental animals. These results along with the observed lowered concentrations of CPIR in the plasma and insulin in the pancreas at birth can be interpreted as evidence that insulin is an inhibitor of its synthesis and secretion in utero and that this abnormal intrauterine environment causes changes that persist into extrauterine life.

Animals↗
PubMed1989

The effect of heterologous gonadotropins on the fecundity of rhesus monkeys.

Ovarian stimulation with heterologous gonadotropins over a period of a single month did not depress the fecundity or fecundability of 50 rhesus monkeys as compared to 60 untreated monkeys in a timed breeding colony. The birth rates, seasonality of births, interbirth intervals, and waiting time to the next pregnancy were not significantly different before treatment, after treatment, or among the untreated. The stillbirth rate was not increased after treatment.

Animals↗
PubMed1987

Metabolism and placental transfer of 125I-proinsulin and 125I-tyrosylated C-peptide in the pregnant rhesus monkey.

125I-Proinsulin or 125I-tyrosylated-C-peptide (125I-tyr-CP) was administered to pregnant Rhesus monkeys by bolus followed by constant infusion to examine placental transfer of these peptides. At the end of each infusion, fetuses were exsanguinated in situ via the umbilical vein. The bolus-constant infusion technique produced a steady state in maternal plasma of immunoprecipitable label, measured using excess insulin or C-peptide antiserum. In animals infused with 125I-proinsulin, analysis of umbilical venous plasma revealed no apparent transfer to the fetus of immunoprecipitable label. In animals infused with 125I-tyr-CP, 3-13% of the umbilical venous plasma radioactivity was immunoprecipitable, representing 1.4-5.8% of the immunoprecipitable radioactivity in maternal plasma at delivery. Gel filtration chromatography of umbilical venous plasma revealed that the immunoprecipitated moiety was a fragment of 125I-tyr-CP. Analysis of maternal plasma showed that the predominant peak of radioactivity represented intact C-peptide. A peak corresponding to the fetal immunoprecipitable peak was also present. Analysis of simultaneous maternal arterial and uterine vein plasma samples showed that degradation of 125I-tyr-CP occurred across the uterus. Studies in one nonpregnant and three postpartum animals indicated that pregnancy increased the rate of metabolism of 125I-tyr-CP. When 125I-tyr-CP was incubated with trophoblastic cells in culture, degradation to a species corresponding on gel filtration to the immunoprecipitable fetal metabolite was found. We conclude that proinsulin, like insulin, does not traverse the placenta. Immunoreactive fragments of C-peptide do cross, however, and pregnancy alters the metabolism of 125I-tyr-CP, probably owing to placental degradation.

Animals↗
PubMed1987

Simian models for AIDS.

The macaque immunodeficiency syndrome has many parallels to AIDS in humans. Affected monkeys develop profound, prolonged T lymphocyte dysfunction and die of lymphomas or opportunistic infections. We recently isolated a virus that we call SIV from four sick macaque monkeys. The morphology, growth characteristics, and antigenic properties of this virus indicate that it is related to the causative agent of human AIDS. The pathogenicity of this newly isolated virus was tested in macaque monkeys. Five of six died between 127 and 352 days following inoculation. The animals developed a wasting syndrome and died with adenovirus pancreatitis and/or pneumonia and primary retroviral encephalitis. Immunological abnormalities in these animals included a decrease in circulating T4+ lymphocytes and depressed peripheral blood lymphocyte proliferative response to pokeweed mitogen. The SIV monkey model holds great promise for testing antiviral agents and for the development of vaccines against AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

3H-dopamine clearance from the intravascular compartment of the maternal and fetal rhesus monkey.

The clearance of epinephrine and norepinephrine from the intravascular compartment has previously been demonstrated in both pregnant and nonpregnant models. With the use of the pregnant rhesus monkey, this study describes the clearance of dopamine from the fetal and maternal intravascular compartments. In both, the dopamine clearance was biphasic with an initial half-life of 1.5 minutes in fetal blood and 1.0 minute in maternal blood. These studies also confirmed that dopamine does not significantly cross the placenta in an intact form. These observations are consistent with those made for the other two major catecholamines.

Animals↗
PubMed1985

Clearance of 3H-dopamine from the amniotic fluid in the rhesus monkey.

Previous studies have suggested that dopamine is the major catecholamine in the amniotic fluid; however, there are few data available concerning the metabolism of this hormone in the amniotic fluid compartment. With the use of acute 3H-dopamine injection studies into the amniotic sac of pregnant rhesus monkeys, the dopamine half-life was observed to be 29 minutes, the amniotic fluid volume was 113 ml, the metabolic clearance rate was 164 ml/hr, and the calculated production rate was 436 ng/hr. The biphasic pattern of dopamine clearance from this compartment suggests that it is cleared from the amniotic sac by mechanisms similar to those used in the intravascular compartment.

Amniotic Fluid↗
PubMed1985

Serologic identification and characterization of a macaque T-lymphotropic retrovirus closely related to HTLV-III.

Human T-lymphotropic virus type III (HTLV-III) is thought to play an etiologic role in the development of the acquired immune deficiency syndrome (AIDS). In this study the serologic characterization of a new simian retrovirus that is related to HTLV-III is described. This new virus, here referred to as STLV-III, was isolated from sick macaques at the New England Regional Primate Research Center. Radioimmunoprecipitation analysis revealed STLV-III-specific proteins of 160, 120, 55, and 24 kilodaltons, all similar in size to the major gag and env proteins of HTLV-III. These antigens were recognized by representative macaque serum samples and human reference serum samples positive for HTLV-III antibodies. Monoclonal antibodies directed to p24, the major core protein of HTLV-III, also immunoprecipitated a 24-kilodalton species in lysates of cells infected with the macaque virus. This HTLV-III-related virus, which naturally infects a nonhuman primate species, may provide a useful model for the study of HTLV-III and the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Colonic mucin composition in primates. Selective alterations associated with spontaneous colitis in the cotton-top tamarin.

Heterogeneity of colonic mucin glycoprotein was examined in rectal mucosal biopsy specimens from a variety of primate species (Saguinus oedipus, n = 18; Macaca mulatta, n = 2; Macaca fascicularis, n = 2; Aotus trivirgatus, n = 2; Saimiri sciureus, n = 2; and Callithrix jacchus, n = 2). After initial separation of radiolabeled mucin and nonmucin glycoproteins solubilized from mucosal biopsy specimens, at least five labeled mucin components were found in monkey rectal mucosa in contrast to the six mucin fractions observed in the human colon. Although primates consistently lacked the earliest eluting component present in human colonic mucin, other mucin components cochromatographed with comparable fractions previously identified in human colonic biopsy specimens. The relative proportions of each fraction were consistent throughout all species except the cotton-top tamarin (S. oedipus), an animal that develops a chronic colitis. The cotton-top tamarin was found to have a markedly reduced amount of one mucin component (IV) in a manner analogous to the reduction in a human mucin fraction previously noted in patients with ulcerative colitis. Sequential evaluation of mucin profiles in cotton-top tamarins (n = 12) treated with sulfasalazine (50 mg/kg X day) or placebo in a 10-wk double-blind crossover study demonstrated the persistence of the selective reduction in tamarin species IV unrelated to disease activity. In contrast, the relative amount of tamarin mucin III was greater in association with increased disease activity than that observed in association with reduced disease activity (46% +/- 11% total mucin vs. 19% +/- 7% total mucin posttreatment).

Animals↗
PubMed1978

A paramyxovirus causing fatal gastroenterocolitis in marmoset monkeys.

A paramyxovirus has been isolated, identified and characterized. The virus causes a disease characterized clinically by severe diarrhea, dehydration and death. Microscopically the disease is characterized as a proliferative gastroenterocolitis with focal necrosis of the mucosa, by giant syncytial cells and eosinophilic intranuclear and intracytoplasmic inclusions. The virus is closely related to measles virus antigenically.

Animals↗