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Biomedical subjects

G Srinivasan

Publications and source records attributed to G Srinivasan.

At least 55 records · Page 3Linked to original sources
PubMed1990

Recombinant human glucocorticoid receptor induces transcription of hormone response genes in vitro.

A recombinant full length human glucocorticoid receptor stimulates transcription in vitro of test genes containing synthetic glucocorticoid and progesterone response elements or murine mammary tumor virus promoter. The receptor expressed in a baculoviral vector is highly active, enhancing transcription of hormone response genes greater than 30-fold even at a receptor concentration of 1.2 nM. The enhancement of transcription is glucocorticoid and progesterone response element-dependent, suggesting that it is a receptor mediated event. In vitro and in vivo treatment with the agonist dexamethasone or with the antagonist Ru486 did not alter significantly the functional activity of partially purified receptor. Kinetic studies suggest that both glucocorticoid receptor and HeLa cell extracts are required for formation of a stable committed transcriptional complex. Our results indicate that the action of glucocorticoid receptor on gene transcription is similar to that defined recently for the progesterone receptor and may be a general mechanism for all steroid receptors.

Animals↗
PubMed1990

Overexpression of full-length human glucocorticoid receptor in Spodoptera frugiperda cells using the baculovirus expression vector system.

We have expressed a full-length human glucocorticoid receptor (hGR) in Spodoptera frugiperda (Sf9) cells using the baculovirus expression vector system (BEVS). The level of expression is approximately 100-fold greater than in CEM-C7 cells. Between 0.5-1.0 mg hGR can be generated per liter of Sf9 cell culture. The expressed hGR is capable of binding glucocorticoids with specificity and high affinity. Covalent labeling with 3H-dexamethasone mesylate and Western blot analysis using a polyclonal antibody indicate that the molecular weight of the expressed protein is approximately 94 k. The nonactivated receptor sediments as a 8-9S complex in sucrose gradients and can be heat activated to a 4S form. The activated receptor is capable of retarding the migration of a 23 base-pair DNA fragment containing the glucocorticoid response element from the tyrosine aminotransferase gene. These data indicate that the expressed GR displays characteristics identical to those of GR from mammalian cells. By scaling up this culture we can, for the first time, obtain enough purified full-length receptor for crystallographic and functional studies which could provide new insight into exactly how hGR works.

Animals↗
PubMed1989

Circle of Willis blood velocity and flow direction after common carotid artery ligation for neonatal extracorporeal membrane oxygenation.

The velocity and direction of blood flow in the circle of Willis arteries were measured in three infants who underwent right common carotid artery ligation for extracorporeal membrane oxygenation treatment. Within 15 minutes of common carotid artery ligation, blood flow was detected in one infant's right middle cerebral artery; however, the velocity was reduced to 50% of the preextracorporeal membrane oxygenation level. The velocity remained 50% to 70% lower than normal during the 88 hours of extracorporeal membrane oxygenation therapy. In the other two infants, the velocity changes were less severe. By 2 to 10 weeks after weaning from extracorporeal membrane oxygenation, the velocities in the left cerebral arteries were increased to 116% to 217% of the corresponding right cerebral vessels. Following common carotid artery ligation, a retrograde direction of flow was noted in the first (A1) segment of the right anterior cerebral artery and in the right posterior communicating artery, whereas the direction of flow was normal in the corresponding vessels on the left. After common carotid artery ligation, the vertebrobasilar and the contralateral internal carotid systems appear to be the main sources of reperfusion of the right cerebral hemisphere via the circle of Willis. Furthermore, because of the known variants of the circle anatomy, a noninvasive pulsed Doppler method could be used to evaluate the flow patterns in the circle of Willis arteries, both before and after common carotid artery ligation for extracorporeal membrane oxygenation.

Arteriovenous Shunt, Surgical↗
PubMed1986

Green vomiting in the first 72 hours in normal infants.

From June 1980 to September 1984, forty-five newborns (weight greater than or equal to 2000 g), initially presumed normal, were seen with bilious vomiting in the first 72 hours and were prospectively followed up. Nine (20%) required surgical intervention, five (11%) had nonsurgical obstruction such as meconium plug or left microcolon, and the remaining 31 (69%) had idiopathic bilious vomiting. Infants with idiopathic bilious vomiting had a benign transient course and resumed feedings by 1 week of age; 30 of the 31 had normal or nonspecific findings on initial plain abdominal roentgenogram. Specific findings on the initial plain abdominal roentgenogram were noted in five infants, and four (80%) of these had a lesion requiring surgical intervention; 56% (5/9) of neonates with surgical lesions had normal or nonspecific findings on the plain abdominal roentgenograms. None developed bowel ischemia or midgut infarction secondary to a volvulus as they were identified by contrast studies shortly after the initial episode of bilious vomiting. Although the majority of "normal" neonates with bilious vomiting do not have a surgical lesion, this study indicates that 56% of surgical cases will be missed if contrast studies are not done.

Age Factors↗
PubMed1986

Glucose homeostasis during anesthesia and surgery in infants.

Baseline, preinduction, postinduction, and postsurgical plasma samples were collected for glucose, insulin, and cortisol in 16 neonates and infants. Glucose infusion rate was maintained constant (mean +/- SD 4.1 +/- 1.2 mg/kg/min) prior to and during surgery; additional fluid losses during surgery were replaced by fluids without dextrose. The weight at the time of surgery was 3,038 +/- 1,397 g. Postnatal age at the time of study ranged from one day to 40 weeks and the duration of surgery was 83 +/- 35 minutes. Plasma glucose values were higher than baseline values soon after induction of anesthesia (88 +/- 11 v 130 +/- 36 mg/dL; P less than .05); postsurgical glucose values were significantly higher than postinduction values (210 +/- 109 mg/dL v 130 +/- 36 mg/dL, P less than .01). Postsurgical plasma glucose had a negative correlation with weight of infants at the time of study (P less than .01; r = .61). Insulin changes were minimal and variable. Cortisol values did not change significantly from baseline values until the end of surgery (11.9 +/- 8.3 v 22.2 +/- 10.6 micrograms/dL; P less than .05). Hyperglycemia (greater than 150 mg/dL) was noted in 10/16 infants. This study indicates that glucose levels should be monitored and that additional fluid losses should be replaced by fluids without dextrose in neonates undergoing surgical procedures since hyperglycemia is a common occurrence.

Anesthesia↗
PubMed1985

Post-natal thyroid function in low birth weight infants; a longitudinal assessment of free thyroxine and thyroid hormone binding globulin.

Because the concentrations of serum free thyroxine (FT4) and thyroid hormone binding globulin (TBG) have not been fully evaluated in preterm infants at the immediate post-natal period, we studied the longitudinal changes of serum FT4 and TBG, along with thyroxine (T4) and thyroid stimulating hormone (TSH), at birth (cord blood), 2 days, 1 week and 2 weeks of age in 7 infants with birth body weight less than or equal to 1000 g, 7 infants with body weight 1001 to 1350 g, 11 infants with body weight 1351 to 2499 g, and 11 full-term infants. Free T4 concentrations were measured by Corning Medical radioimmunoassay (RIA) kit. The infants with extremely low birth weight (ELBW) (body weight less than or equal to 1000 g) showed precipitous declines of total T4 and, to a lesser extent, of FT4 concentrations at 1 and 2 weeks of age. These post-natal T4 and FT4 decreases in ELBW neonates have not previously been reported. The clinical significance of this finding remains, speculative, but it may be due to metabolic or nutritional problems related to extreme prematurity itself. This study suggests that measurement of FT4 is a useful adjunct to the assessment of ELBW infants with very low T4 values, if done between 1 to 2 weeks of age, and could be used as a primary hypothyroid screening tool instead of T4 measurements, provided that an FT4 assay is developed that uses the elute of blood spotted on filter paper.

Age Factors↗
PubMed1985

Decreased plasma glucose following indomethacin therapy in premature infants with patent ductus arteriosus.

The effect of indomethacin on carbohydrate metabolism was studied in six premature infants with significant patent ductus arteriosus (mean +/- S.D., birth weight 1,066 +/- 244 gm, gestational age 30 +/- 1.6 weeks). All infants were in a glucose steady state between 50 and 100 mg/dl over a 2-hour period before indomethacin administration. There was a significant fall in plasma glucose at 1, 6, 12, and 24 hours following intravenous indomethacin infusion. Since there was no significant change in insulin levels from the baseline, the mechanism of indomethacin-mediated lack of prostaglandin inhibition of insulin release was not substantiated. Based on this study, plasma glucose levels should be followed closely in the first 24 hours following intravenous indomethacin administration.

Birth Weight↗
PubMed1984

Rotavirus infection in normal nursery: epidemic and surveillance.

Human rotavirus (HRV) epidemics have not been reported in normal full-term newborn nurseries in the US. This report describes an epidemic from April 27 to May 6, 1982 in which 23 infants were infected. Diagnosis was confirmed with Rotazyme (Abbott) in 82% (23/28) of the neonates screened. Five were asymptomatic; in the remaining 18 cases, the symptoms were usually mild and self-limited. Transient shedding of the virus was found in 8% (4/52) of personnel screened, and only one of them was symptomatic. Control measures included the following: strict cohorting, closure of transitional nursery, enteric precautions and wiping of horizontal surfaces with 95% ethyl alcohol which has been shown to be an effective virucidal agent for rotavirus in laboratories. Follow-up in 80 of 108 contact neonates born during the epidemic showed only two mildly symptomatic cases after discharge. During an 11-month period of surveillance, 33% of neonates (1,688/5,054) born at Cook County Hospital were screened for excretion of virus in stools; only 3.6% of infants (61/1,688) were positive by Rotazyme and none were symptomatic. This report suggests that strict measures are helpful in control of HRV epidemic gastroenteritis and asymptomatic shedding need not be as high as the previously reported incidence of 40% to 50%.

Chicago↗
PubMed1983

Pleural-based changes on chest X ray after irradiation for primary breast cancer: correlation with findings on computerized tomography.

In treating breast cancer with excisional biopsy and irradiation, a volume of lung underlying the breast and chest wall receives significant doses of irradiation. This irradiation can produce pleural and pulmonary changes that can be seen on routine chest radiographs. In five such cases, we have examined pre and post-treatment computerized tomograms of the chest and show that these radiographic changes are pleural-based and lie within the high dose radiation volume. Failure to correct radiation treatment plans for the influence of lung density results in an increased dose to lung and pleura that could, in theory, exacerbate pulmonary and pleural radiation effects.

Adult↗
PubMed1982

Postnatal thyroid function in low birth weight infants: a cross-sectional assessment of free thyroxine and thyroid hormone binding globulin.

To investigate the significance of low serum thyroxine in premature infants, serum FT4, T4, TSH and TBG were measured in 7 infants with BW less than 1000 g, 8 infants with BW 1001 to 1350 g, 9 infants with BW 1351 to 2499 g, and 11 full-term infants. FT4 concentrations were lower in the LBW infants than in the FT infants. Percent FT4 values in the infants with BW less than 1000 g were the highest in the groups studied, so that FT4 concentrations in those infants did not fall proportionally with the marked T4 decrease. TBG concentrations were lower in the VLBW infants (less than BW 1350 g) than in the FT infants, and were positively correlated with BW and GA. This study suggests that in infants with lower birth weight there is a mechanism to prevent a decrease in FT4 concentrations associated with total T4 decrease. This fact may be a reason for euthroidism in small premature infants with low T4. Measurements of FT4 may be a useful adjunct to assessment of thyroid function in the VLBW infants with low T4.

Alpha-Globulins↗
PubMed1982

Decreased plasma glucose following indomethacin therapy in premature infants with patent ductus arteriosus.

In the course of a double-blind controlled trial of intravenous indomethacin therapy in premature infants with patent ductus arteriosus, plasma glucose was evaluated in 47 infants before and at 24, 48, and 72 hours following the medication. Twenty-two infants were assigned to the control group and 25 were in the indomethacin group. Significantly lower plasma glucose was noted at 24 (P less than 0.01) and 48 (P less than 0.05) hours in the indomethacin group as compared to the control group. There was a significant inverse correlation between the plasma glucose and the corresponding plasma indomethacin concentration (P less than 0.05) and between the plasma glucose and the corresponding plasma indomethacin concentration-time integral (P less than 0.01) at 24, 48, and 72 hours after drug administration, suggesting that the decreased plasma glucose may be related to indomethacin therapy. The results of this study indicate that endogenous prostaglandin may play a role in glucose homeostasis in premature infants.

Blood Glucose↗
PubMed1982

Fever in full-term newborns in the first four days of life.

Over a period of 18 months, 100 full-term newborns developed an axillary or a rectal temperature greater than or equal to 37.8 C during the first four days of postnatal life. These febrile term newborns represented 1% of all full-term newborns in the normal nursery. Of the febrile newborns, 10% had culture-proven bacterial disease (BD). Fever developed in 54%, 27%, 13%, and 6% on the first, second, third, and fourth days, respectively. In 17 newborns fever developed within the first hour of life; 13 of these had mothers with fever and two others were under a radiant warmer in the birth room. Fever occurring on the third day of postnatal life had a significantly higher chance of being associated with BD than fever occurring at any other time in the first four days of postnatal life. Newborns with temperature greater than or equal to 39 C had a significantly higher incidence of BD than newborns with temperature less than 39 C. The incidence of fever among breast-fed newborns (0.98%) was similar to that of formula-fed newborns (1.01%). Of the 100 febrile newborns, 45 had other symptoms compatible with BD, and eight of these had proven BD (group B Streptococcus in five, group D Streptococcus in one, Shigella D in one, and Propionibacterium species in one). The two other febrile newborns with proven BD had no other symptoms of infection (group B Streptococcus and Escherichia coli). Mean WBC count of febrile newborns with BD was significantly lower than that of febrile newborns without BD. Only three febrile newborns had WBC count less than 5,000/cu mm and two of them had proven BD. Febrile newborns should be evaluated and treated with antibiotics when they have symptoms of infection other than fever or when the fever persists or recurs.

Age Factors↗
PubMed1981

Metabolic effects of theophylline in preterm infants.

A loading dose of theophylline produces significant metabolic changes, including increase of plasma glucose concentration and an early rise in serum insulin in some infants. The chronic effects of theophylline on plasma glucose, serum insulin, and glucagon are not known at this time. The potential for development of metabolic derangements must be kept in mind when theophylline is used for protracted periods in premature infants.

Apnea↗