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Biomedical subjects

U Desai

Publications and source records attributed to U Desai.

At least 19 recordsLinked to original sources
PubMed2000

Role of arginine 129 in heparin binding and activation of antithrombin.

The contribution of Arg(129) of the serpin, antithrombin, to the mechanism of allosteric activation of the protein by heparin was determined from the effect of mutating this residue to either His or Gln. R129H and R129Q antithrombins bound pentasaccharide and full-length heparins containing the antithrombin recognition sequence with similar large reductions in affinity ranging from 400- to 2500-fold relative to the control serpin, corresponding to a loss of 28-35% of the binding free energy. The salt dependence of pentasaccharide binding showed that the binding defect of the mutant serpin resulted from the loss of approximately 2 ionic interactions, suggesting that Arg(129) binds the pentasaccharide cooperatively with other residues. Rapid kinetic studies showed that the mutation minimally affected the initial low affinity binding of heparin to antithrombin, but greatly affected the subsequent conformational activation of the serpin leading to high affinity heparin binding, although not enough to disfavor activation. Consistent with these findings, the mutant antithrombin was normally activated by heparin for accelerated inhibition of factor Xa and thrombin. These results support an important role for Arg(129) in an induced-fit mechanism of heparin activation of antithrombin wherein conformational activation of the serpin positions Arg(129) and other residues for cooperative interactions with the heparin pentasaccharide so as to lock the serpin in the activated state.

Antithrombins↗
PubMed2000

Hyperthyroidism in children.

This study was done to characterize the clinical features, laboratory parameters and response to therapy and outcome of childhood hyperthyroidism. The evaluation included history, examination, laboratory investigations: serum T3, T4, TSH, free T3, free T4 by RIA or immunochemiluminescence (IC), antithyroid antibodies by standard techniques, bone age (BA) by Greulich and Pyle's method, clinical and laboratory response to treatment, and follow-up of 15 children with hyperthyroidism seen in past eight years. Age of onset, presentation, nature and duration of symptoms, family history, anthropometry and signs of hyperthyroidism were recorded. There were 10 girls and 5 boys (2:1). Three families had a history of thyroid disorders. Mean ages of onset and presentation were 8.25 +/- 3.4 and 9.27 +/- 3.2 years respectively. Clinical features included weight loss, heat intolerance and sweating, diarrhoea, behavioral problems, ophthalmopathy and tachycardia. BA was advanced. Serum T3 (mean = 4.29 +/- 1.77 ng/mL), T4 (18.75 +/- 5.64 micrograms/dL), FT3 (7.11 +/- 4.58 pg/mL) and FT4 (2.93 +/- 0.29 ng/mL) were markedly elevated. TSH was suppressed. Anti-microsomal antibodies (AMA) and anti-thyroglobulin antibodies (ATG) were positive in five. They were started on standard treatment with carbimazole 0.5-0.7 mg kg-1. Clinical and biochemical euthyroidism was achieved within 2.5 to 6 months in all, after which the drug was tapered, however, they required treatment for 2 years to 7.5 years. Four children were retreated for relapse and are now euthyroid and off treatment. Childhood hyperthyroidism requires long term treatment and careful monitoring. This study shows a remission rate of 67%.

Adolescent↗
PubMed2000

Ectopia cordis.

Ectopia cordis is a rare congenital defect in which the heart is placed externally on the surface of the chest. This article describes the embrylogic events that lead to the various classifications of the defect and how they possibly explain the process of its unusual occurrence in children. While survival in some cases is possible, the ultimate repair is difficult and survival is rare. The most extreme forms of ectopia cordis, especially those with intracardiac defects, have a poor prognosis. Several cases of this rare anomaly with primary repair and staged repair are discussed.

Cardiac Surgical Procedures↗
PubMed1994

Toxic effects of fatty acid anilides on the oxygen defense systems of guinea pig lungs and erythrocytes.

Toxic oil syndrome (TOS) is caused by ingestion of denatured edible oils. Even though the etiology and pathogenesis of this disease are not fully known, it is quite clear that generation of free radicals caused by ingestion of fatty acid anilides is responsible for the pathogenetic mechanism in many TOS patients. Fatty acid anilides may also alter the free radical status of lungs and erythrocytes; this possibility may shed some light on understanding toxic oil syndrome. The present study describes the effects of oral administration of fatty acid anilides on the activities of major enzymes involved in the oxygen defense systems of lungs and erythrocytes. Feeding fatty acid anilides caused an increase in the superoxide dismutase (SOD) activity in erythrocytes, whereas it caused a decrease in the SOD activity in lungs. GSH-Px activity was not significantly changed in erythrocytes but was decreased in lungs. Although the activity of catalase was increased only by a higher dose in the erythrocytes, it was not affected in the lung at any dosage. Even though the ingestion of fatty acid anilides caused an increase in the SOD activity in the erythrocytes and a decrease in the SOD activity in the lungs, there was an increase in the lipid peroxidation in both cases. The increase in lipid peroxidation in erythrocytes is probably caused by the accumulation of H2O2, and that in the lungs is due to the accumulation of superoxide anion.

Anilides↗
PubMed1994

Development of pancellular toxicity in guinea pig lung by ingestion of oleylanilide.

Toxic oil syndrome (TOS), characterized by widespread thromboembolism, vasculotoxicity, and ARDS, develops in humans ingesting denatured edible oils. The mechanism(s) involved in targeted vasculocentric damage in this multi-system disorder is not known. Oleylanilide (OA) was synthesized and fed to male, young adult guinea pigs by gavage for 30 days at doses of 35, 50, and 100 mg/kg/day in groups of six animals each respective to weight. Controls were fed olive oil. Oleylanilide fed animals gained less weight than controls. At the end of experiment, right lungs were inflation fixed in appropriate fixative for histology and transmission electron microscopy (TEM) and left lungs were frozen at -70 degrees C for biochemical analyses. The activity of glycerophosphate acyltransferase (GAT) and cholinephosphotransferase (CPT), two key enzymes involved in phospholipid biosynthesis, were decreased in lung due to OA ingestion. All doses of OA induced marked perivascular and peribronchoiolar monocytic infiltrates that often formed prominent nodules; segmental vascular smooth muscle cell proliferation and derangement of myocytic polarity, subendothelial foamy infiltrates, and edema; nuclear pyknosis and dropout in vascular and bronchial targetoid myocytes; and denudation of bronchiolar epithelial cells. Alveoli contained large numbers of monocytes, macrophages, red cells, edema, and debris. Transmission electron microscopy showed type I cell cytoplasmic ballooning and disintegration of type I cell; contracted and blebbed endothelial cells, fibrin thrombi in capillaries, intracellular megalamellar bodies in type II cells, and surfactant lamellae; and liposomes and fine granular precipitates within alveoli, and contraction and lift off of bronchiolar epithelial cells. Monocytes, mast cells, and eosinophils infiltrated bronchial walls. Furthermore, there was deposition of electron dense particles on the surface of the alveolar wall.(ABSTRACT TRUNCATED AT 400 WORDS)

Anilides↗
PubMed1994

Laparoscopic assisted colorectal surgery.

Forty-nine consecutive patients underwent laparoscopic assisted colorectal surgery for benign and malignant lesions of the colon. Thirty-eight of the 49 operations (78%) were completed successfully with laparoscopic assistance. A large tumor bulk or dense adhesions were the most common reasons for conversion to laparotomy. Twenty-eight of the 38 patients (74%) in the laparoscopically completed group were tolerating a diet by postoperative day 2, and 31 (82%) passed flatus or a bowel movement by the third postoperative day. The mean postoperative hospital stay for this group was 4.8 days, which compared very favorably to that reported in the literature for traditional open colorectal operations. Twelve patients developed complications, for a 24% morbidity in the series. However, only 3 (6%) of these complications were related to the laparoscopic part of the procedure. Inspection of the pathologic specimens revealed adequate margins and a lymph node harvest that averaged 11 nodes per specimen. We concluded that laparoscopic assisted colorectal surgery is a safe and feasible technique, which may be associated with a faster return of bowel activity and a shorter hospital stay. Although the extent of resection appears comparable to that of laparotomy, it is too early to assess long-term outcome when it is applied in the treatment of malignancy.

Adult↗
PubMed1994

Laparoscopic treatment of colovesical fistulas: technique and report of two cases.

Colovesical fistulas are a serious complication of diverticular disease. Management by one-stage resection and anastomosis has resulted in lower morbidity and shorter hospital stay. Nevertheless, hospital time remains long, approaching an average of 2-3 weeks. Here we describe our technique of laparoscopic approach to colovesical fistulas. Our initial experience suggests that this is a safe operation with minimal pain, absent ileus, and a short postoperative stay.

Adult↗
PubMed1991

A technique for retinal pigment epithelium transplantation for age-related macular degeneration secondary to extensive subfoveal scarring.

We describe the surgical excision of submacular scar in end-stage age-related macular degeneration and transplantation of autologous and homologous retinal pigment epithelial (RPE) cells. The technique involves the preparation of a large retinal flap encompassing the macula and the arcades, removal of the submacular scar, and replacement of the RPE cells, using either an autologous pedicle graft or homologous RPE cells and Bruch's membrane. Fourteen months following the procedure, visual acuity in a patient with a pedicle graft had improved from counts fingers to 20/400 and the patient fixated over the transplanted RPE cells. After 10 months, a homologous graft in a second patient had become encapsulated with a fine subretinal membrane without neovascular tissue; visual acuity had not improved. No intraoperative or postoperative complications resulting from the surgery occurred in either patient.

Aged↗
PubMed1985

Pregnancy-induced hypertension: development of a model in the pregnant primate (Papio anubis).

Experiments were performed on two groups of pregnant baboons. In the experimental group, the subrenal aortic blood flow was reduced by 58% of its original value at 100 days of gestational age. In the control group, the blood flow was measured but not restricted. In the experimental group fetal death occurred in three of 12 animals following the use of a single left-flank incision to approach both the renal artery and the abdominal aorta. In the control group, pregnancies in eight of nine animals went successfully to 165 days. In the experimental group the development of hypertension, a decrease in plasma renin activity, an increase in renal resistance, an increase in serum uric acid, and the development of glomerular changes consistent with those seen in human pregnancy-induced hypertension were noted. These studies demonstrate that pregnancy-induced hypertension can be produced experimentally in a pregnant baboon, and this model should prove useful in expediting studies on the pathophysiologic features and treatment of this condition.

Animals↗
PubMed1985

Efficacy of S-2441, a synthetic oligopeptide, in a rat model for gram-negative bacteremia.

In vitro effects of S-2441, H-D-Pro-Phe-Arg-NH-Heptyl, include potent anti-bradykinin activity and broad-spectrum inhibition of serine proteases involved in the coagulation cascade. In this study, rats infused with 7.8 X 10(8) viable Escherichia coli were treated either with saline (group A) or with intravenous (0.1 mg) and intraperitoneal (0.4 mg) doses of S-2441 (group B). Survival rates for groups A and B were 68% and 98%, at 12 hours (P less than 0.001), and 37% and 73% at 24 hours (P less than 0.001), respectively. Hematologic studies revealed that S-2441 significantly inhibited E. coli-induced prolongation of prothrombin time and partial thromboplastin time as well as a rapid decrease in the values of factor X, anti-thrombin III, and fibrinogen. In addition, S-2441 attenuated E. coli-induced hypoglycemia and a marked reduction of serum complement level. Ultrastructural evaluation of the liver demonstrated that S-2441 prevented the development of extensive sinusosoidal microthrombosis and hepatocellular necrosis. The results indicate that S-2441 affords protection in lethal gram-negative bacteremia owing in part to attenuation of disseminated intravascular coagulation and complement-mediated reactions. The findings are consistent with the concept that S-2441 and related oligopeptides modulate serine protease-mediated responses involving inhibition of active enzymes with competitive antagonism of pharmcologically active products formed during the activation of coagulation, fibrinolytic, kallikrein, and complement systems.

Animals↗
PubMed1984

Demonstration of C5 cleaving activity in bronchoalveolar fluids and cells: a mechanism of acute and chronic alveolitis.

Recently, we have demonstrated that preformed chemotactic fragments derived from C5 (C5fr), when instilled intratracheally, induce an intense acute alveolitis. An intense intrapulmonary inflammatory reaction, characterized by accumulation of large numbers of neutrophils in the alveolar spaces, also resulted from intratracheal instillation of purified human C5. Since purified C5 does not induce PMN chemotaxis in vitro and presumably native C5 is not phlogistic in vivo, a mechanism for C5 cleavage productive of chemotactic fragments may be operative within the lung. To explore the possibility that pulmonary-mediated fragmentation of C5 occurred, both in vitro and in vivo studies were undertaken. As described in this paper, extensive cleavage of 125I-labeled C5 was demonstrated in the bronchoalveolar lavage fluids (BALF) of hamster lungs previously instilled with 125I-labeled C5. In vitro incubation of 125I-labeled C5 with normal hamster lung lavage components, cells, and lavage fluid also cleaved 125I-labeled C5. Bioassay of such in vitro reactions also revealed potent chemotactic activity for polymorphonuclear leukocytes. A potent C5-cleaving activity was detected in fluid of normal bronchoalveolar lavage (BAL) recovered from normal hamster lungs. This BALF "enzyme activity" selectively cleaved C5 in vitro, producing potent C5-related chemotactic fragmentation products, but it did not fragment C3 nor did it produce C3 chemotactic factors in vitro. Cleavage of C5 by alveolar macrophages that produces chemotactic factors has previously been attributed to an acid protease of lysosomal origin. This "enzyme activity" is apparently distinct from elastase, collagenase, and trypsin since it is not inhibited by alpha 1-antitrypsin. In separate studies, we have recently demonstrated the ability of isolated lung cells to synthesize and secrete C3 and C5 in vitro. Thus, these studies suggest that the lung may intrinsically have the capacity to regulate inflammatory reactions by the localized production of both complement components (C3 and C5) as well as complement-activating systems (e.g., C5-cleaving activity of BALF).

Acute Disease↗
PubMed1984

The lymphatic pathology of Brugia pahangi in nude (athymic) and thymic mice C3H/HeN.

The nude (congenitally athymic) mouse, C3H/HeN is highly susceptible to infection with Brugia pahangi (Nematoda: Filarioidea). Normal, hairy mice show a strong thymus-dependent resistance and usually terminate the infection in the larval stages. The present study examined chronological histopathologic changes in the lumbar lymph nodes and adjacent lymphatic vessels of both hosts. In thymic mice, lymphangitis and perilymphangitis reached a maximum 14 to 17 days PI, about the time of disappearance of live worms. The infiltrate showed characteristics of both acute and chronic inflammation: eosinophils, neutrophils, eosinophilic precipitates, and sometimes necrotizing lymphangitis, as well as macrophages and plasma cells. The cellular infiltrate in nude mice was weaker and developed more slowly. Inflammatory responses to identifiable dead worms were seen in both types of hosts but appeared more frequently in thymic mice. Although variable in both models, the granulomas of thymic mice generally showed more tendency to cavitation, greater macrophage or epithelioid cell infiltration, more granulocytes, and appeared to be more destructive than the foreign body responses of nude mice. Whereas lymphangiectasis was generally progressive in nude mice, it was arrested before the end of the third week in thymic mice. In thymic mice, at maximum lumbar lymph node size (17 days), there were large areas of lymphocyte hyperplasia and heavy infiltration of plasma cells. Most nodes returned to normal mean size by the end of the second month. Little or no reactivity was seen in athymic mouse nodes. Our results suggest that some lesions of lymphatic filariasis are potentially thymus-independent: lymphatic fibrosis, lymphangiectasis, accumulations of macrophages and giant cells around disintegrating worms, calcification of worms, intralymphatic thrombosis, and moderate vascular infiltrates including eosinophils.

Animals↗
PubMed1981

Two phospholipase pools for prostaglandin synthesis in macrophages.

Macrophages in culture produce prostaglandins in response to a variety of phagocytic and non-phagocytic stimuli. As prostaglandins are not stored in cells, and mammalian cells contain very little free arachidonic acid, synthesis and release of prostaglandins depends on the release of the precursor, arachidonic acid, from cell lipids. Many agents that stimulate cell prostaglandin production act by releasing arachidonic acid, presumably by activating phospholipase A2 (refs 10, 11) or phospholipase C (refs 12, 13), depending on the cell system used. We have shown previously that rabbit alveolar macrophages secrete arachidonic acid as well as prostaglandins in response to phagocytic stimuli. This secretion depends not on particle attachment, but rather on interiorization of the particles. Furthermore, the time course of prostaglandin and arachidonic acid secretion does not parallel that of particle engulfment per se, but of the release of lysosomal enzymes, indicating that the release of arachidonate and prostaglandin is associated with the latter. We now describe experiments which suggest that these are two independent pools of phospholipases in macrophages, one in the lysosomes and one elsewhere.

Animals↗
PubMed1981

The effect of 2% CO2, 100% O2, theophylline and 15% O2 on "inspiratory drive" and "effective" timing in preterm infants.

We studied 20 preterm infants (B.W. 1440 +/- 80 g (S.E.); G.A. 33 +/- 1 wk) to determine the effect of respiratory stimulants and depressants on respiratory output as measured by VE = VT . f, and VE = VT/Ti . Ti/Ttot. These 20 infants were divided in four groups of five infants. Each group received a respiratory stimulant (2% CO2, 100% O2 or theophylline) or'a respiratory depressant (15% O2). VT/Ti is mean inspiratory flow and represents a mechanic translation of neuronal output. Ti/Ttot is a dimensionless number and has been defined as effective timing. Each study consisted of 3-5 min while the infant breathed 21% O2, followed by 5 min breathing 2% CO2, 100% O2 or 15% O2. The effect of theophylline was assessed by 48-72 h after the initial dose. The respiratory stimulants caused an increase in VT with little or no change in f; 15% O2 produced a decrease in f primarily. According to the newer approach, 2% CO2, 100% O2 and theophylline produced an increase in "inspiratory drive" with little or no change in "effective" timing; 15% O2 decreased "effective" timing primarily via an increase in Te. These findings suggest that the paradoxical decrease in ventilation during hypoxia in preterm infants may not be solely dependent on the central depressant effects of O2. At least in part, the mechanism may be due to a direct action of low O2 on elements controlling expiratory time.

Carbon Dioxide↗