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Biomedical subjects

J Sharma

Publications and source records attributed to J Sharma.

At least 55 records · Page 3Linked to original sources
PubMed1993

Recombinant insulin-like growth factor binding protein-1 inhibits IGF-I, serum, and estrogen-dependent growth of MCF-7 human breast cancer cells.

The insulin-like growth factors (IGFs) are potent mitogens for breast cancer cells and their activity is modulated by high affinity binding proteins (IGFBPs). We have recently shown that IGFBP-1 purified from human amniotic fluid neutralizes IGF-I-dependent growth of MCF-7 cells. In this study we examined the effects of recombinant IGFBP-1 (rBP-1) on IGF-I, estradiol (E2), and serum-induced monolayer and anchorage independent growth (AIG) of MCF-7 cells. Under serum-free conditions, rBP-1 had no effect on MCF-7 basal monolayer growth. However, 40 nM rBP-1 completely blocked the mitogenic action of both IGF-I and 5% charcoal stripped serum (CSS). This concentration of rBP-1 partially inhibited E2-induced growth, while 80 nM rBP-1 completely abolished E2 mitogenicity. The addition of either excess IGF-I or 5 nM [Arg3]IGF-I, a species that does not bind IGFBPs, neutralized rBP-1 inhibitory effects. In AIG assays, 80 nM rBP-1 reduced colony number by at least 70% and decreased colony size in all treatment groups compared to control. We examined rBP-1 effects on both IGF-I binding to MCF-7 membranes and activation of type I IGF receptor (IGFR1) and found that 80 nM rBP-1 reduced IGF-I receptor binding to levels of nonspecific binding and completely abolished ligand-dependent IGFR1 phosphorylation. However, neither treatment with 5% CSS nor exposure to E2 resulted in IGFR1 phosphorylation suggesting that different mechanism(s) are responsible for rBP-1 inhibitory action under this condition. Our data suggest rBP-1 may serve as an antagonist of human breast cancer growth by interfering with growth factor-mediated cell proliferation.

Analysis of Variance↗
PubMed1992

Treatment of prolonged ventricular fibrillation. Immediate countershock versus high-dose epinephrine and CPR preceding countershock.

BACKGROUND: Early countershock of ventricular fibrillation has been shown to improve immediate and long-term outcome of cardiac arrest. However, a number of investigations in the laboratory and in the clinical population indicate that immediate countershock of prolonged ventricular fibrillation most commonly is followed by asystole or a nonperfusing spontaneous cardiac rhythm, neither of which rarely respond to current therapy. The use of epinephrine in doses greater than those currently recommended has recently been shown to improve both cerebral and myocardial perfusion during cardiopulmonary resuscitation (CPR). The purpose of this study was to compare cardiac resuscitation outcome between immediate countershock of prolonged ventricular fibrillation with high-dose epinephrine therapy and conventional CPR before countershock of prolonged ventricular fibrillation in a canine model. METHODS AND RESULTS: After sedation, intubation, induction of anesthesia, and instrumentation, ventricular fibrillation was electrically induced in 28 dogs. After 7.5 minutes of ventricular fibrillation, animals were randomly allocated to two treatment groups: group 1, immediate countershock followed by recommended advanced cardiac life support (ACLS) interventions, or group 2, 0.08 mg/kg epinephrine and manual closed-chest CPR before countershock and ACLS. In both groups, ACLS was continued until a spontaneous perfusing rhythm was restored or for 20 minutes (total arrest time, 27.5 minutes). A spontaneous perfusing rhythm was restored in three of 14 group 1 animals and in nine of 14 group 2 animals (p = 0.014 by sequential analysis method of Whitehead). Coronary perfusion pressure (aortic minus right atrial pressure during CPR diastole) before countershock was significantly greater in group 2 (21 +/- 7 mm Hg) when compared with mean circulatory pressure in group 1 (9 +/- 8, p less than 0.01). CONCLUSIONS: The findings of this study suggest that a brief period of myocardial perfusion before countershock improves cardiac resuscitation outcome from prolonged ventricular fibrillation.

Animals↗
PubMed1992

Solitary rectal ulcer syndrome and colitis cystica profunda--a clinico-pathological review.

Twenty cases of solitary rectal ulcer syndrome (SRUS) and three cases of colitis cystica profunda (CCP) diagnosed between 1985 to 1990 were studied retrospectively. Clinical features, sigmoidoscopic findings and histopathology of the above lesions were reviewed. Haematoxylin and Eosin, Masson's Trichome, and high iron diamine Alcian blue staining was done in all the cases. Histopathologic examination helps in diagnosing the benign condition of the rectum viz. SRUS and CCP which are considered malignant clinically. Since an overlap of histopathological features were seen in SRUS and CCP, both can be considered as one entity, which has been highlighted in our study. Fibromuscular obliteration of lamina propria is the hallmark of the lesion.

Adolescent↗
PubMed1991

Ionized hypocalcemia during prolonged cardiac arrest and closed-chest CPR in a canine model.

STUDY BACKGROUND: Free or ionized calcium (Ca+2) is known to play a critical role in normal cardiovascular function, and Ca+2 administration in the setting of ionized hypocalcemia has been shown to improve indexes of cardiac function. The value of Ca+2 administration in the setting of cardiac arrest and resuscitation is unproven and controversial, in large part because ionized Ca+2 levels during cardiac arrest and resuscitation have not been adequately studied and exogenous calcium therapy may worsen ischemic cellular injury. STUDY PURPOSE: To measure free calcium during prolonged cardiac arrest and CPR in a canine model. METHODS AND MEASUREMENTS: Central arterial and venous catheters were positioned in nine dogs, and ventricular fibrillation (VF) was induced electrically. After seven and one-half minutes of VF, countershocks were administered, and CPR was initiated and performed in accordance with current recommendations for 20 minutes. At five-minute intervals during resuscitation efforts, arterial pH, ionized Ca+2, and lactate as well as aortic pressure were measured. RESULTS: During resuscitation, average systolic arterial pressure was 50 mm Hg. Within five minutes of instituting CPR, ionized Ca+2 significantly decreased from control values (5.1 +/- 0.1 at control to 4.0 +/- 0.1 mg/dL); after 20 minutes of attempted resuscitation, it averaged 3.2 +/- 0.2 mg/dL (P less than .05 vs control). There was no change in total Ca+2 during the arrest period (9.2 +/- 0.5 at control to 8.6 +/- 0.8 mg/dL at 27.5 minutes). Arterial lactate significantly increased throughout the arrest and resuscitation period (1.9 +/- 0.2 at control to 7.5 +/- 0.4 mM/L at 27.5 minutes). A significant correlation was demonstrated between ionized Ca+2 and lactate concentrations (r = -.72, P less than .001) but not between ionized calcium and pH (r = -.22, P greater than .20). CONCLUSION: Ionized hypocalcemia occurs during prolonged cardiac arrest and resuscitation, and ionized hypocalcemia during prolonged arrest and resuscitation may be due to binding by lactate, as has been demonstrated in vitro.

Animals↗
PubMed1988

Internal fixation in 50 cases of Galeazzi fracture.

Fifty Galeazzi fracture dislocations were treated by early open reduction, internal fixation, and cancellous bone grafting. After 1 year, 40 cases were good, 8 fair, and 2 poor. We conclude that early open reduction and rigid internal fixation reestablishes the normal relationship of the fractured fragments and the distal radioulnar joint without repair of the ligaments.

Adolescent↗
PubMed1987

Buffers and H2O2 reduce neuronal death and/or enhance differentiation of neurons and astrocytes in dissociated mouse brain cultures.

Tissue of the mammalian central nervous system (CNS) undergoes complex and uncoordinated pathological responses upon injury. Efforts to develop pharmacological approaches to achieve functionally meaningful regeneration largely have been unsuccessful. Assuming that anoxia and drop in tissue H are initiating factors in most pathological sequences consequent to CNS injury, we studied the effects of increasing the buffering and oxygenating capacities of the medium on dissociated embryo brain cultures. The presence of H2O2 in the medium led to greatly enhanced neuronal survival and/or differentiation. Increased buffering capacity favored enhanced neurite outgrowth with remarkable elongation of fibers. A combination of the two gave a synergistic effect in which both of the above responses were seen. Both buffers and H2O2 enhanced astrocytic differentiation and extension of processes while reducing DNA synthesis. The results favor the view that attempts to encourage self-repair in CNS tissue or to enhance repair of CNS damage with potential therapeutic agents or procedures should be carried out in the context of a near optimal environment in which, at the least, pH and pO2 values are stably maintained within normal operational limits.

Animals↗
PubMed1987

Dehydroepiandrosterone and its sulfated derivative reduce neuronal death and enhance astrocytic differentiation in brain cell cultures.

Human studies of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have shown age-related changes in serum levels of these two sex hormone precursors. The levels of both DHEA and DHEA-S are characterized by monotonic decreases after puberty in females and after 20-24 yr of age in males. Further studies have shown that DHEA and DHEA-S levels are significantly low or close to minimal at ages when the incidence of senile dementia of Alzheimer's type (SDAT) begins to increase. We propose that DHEA and DHEA-S play a significant role in normal function of neuronal cells and that supplementation with them may prevent neuronal loss and/or damage. In the present study, using methods of immunocytochemistry, autoradiography, and scanning electron microscopy, we show that a supplement of as little as 10(-8) M DHEA or DHEA-S greatly increases neuronal survival and differentiation and reduces astroglial proliferation rates in mouse brain cells in cultures. These results suggest that correcting the DHEA and the DHEA-S deficit may prevent and/or improve the SDAT condition in humans.

Animals↗
PubMed1985

Numbers of myelinated and unmyelinated axons in the dorsal, lateral, and ventral funiculi of the white matter of the S2 segment of cat spinal cord.

The present work determines the numbers of myelinated and unmyelinated axons in the dorsal, lateral, and ventral funiculi of the S2 segment of the cat spinal cord. The major finding is that unmyelinated axons are almost as numerous as myelinated axons in these pathways. The myelinated axons tend to be distributed uniformly, although there is a slight concentration of these fibers in the dorsal part of the lateral funiculus. By contrast, the unmyelinated fibers, although found in significant numbers in all parts of these funiculi, concentrate in the dorsal part of the lateral funiculus and in the dorsal funiculus. Of particular note are the unmyelinated fibers in the dorsal funiculus, because it is highly likely that some of these are sensory. The findings in this study will serve as a basis for experimental studies to determine the numbers, locations, and types of unmyelinated fibers in the white matter of the mammalian cord.

Animals↗
PubMed1980

Variable levels of plasma catecholamines and dopamine beta-hydroxylase in hemodialysis patients.

Plasma norepinephrine (NE), epinephrine (EPI), dopamine (DPM), dopamine beta-hydroxylase (DBH), and renin were measured in patients undergoing maintenance hemodialysis. The predialysis NE, EPI, and DPM concentrations were lower than normal at 29, 7.3 and 4.8 pg/ml, respectively. The NE level increased in the erect posture to 100 pg/ml at 30 min. Levels were also measured during the postdialysis period, and were approximately the same as in normal subjects, but lower than previously published values for patients undergoing hemodialysis. In the predialysis period, NE and renin correlated upon assumption of the upright posture. It is concluded that maintenance hemodialysis can be carried out without a major distortion of the plasma catecholamine levels.

Adult↗