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Biomedical subjects

H Desai

Publications and source records attributed to H Desai.

At least 19 recordsLinked to original sources
PubMed2002

Platelet-CD40 ligand interaction with melanoma cell and monocyte CD40 enhances cellular procoagulant activity.

Platelet-tumor cell interactions are believed to be important in tumor metastasis. Tumor cell tissue factor (TF) expression enhances metastasis and angiogenesis, and is primarily responsible for tumor-induced thrombin generation and the formation of tumor cell-platelet aggregates. Activated platelets express and release CD40 ligand (CD40L), which induces endothelial TF expression by ligation to CD40. We investigated the effect of platelet-derived CD40L on the TF activity of human CD40-positive melanoma cells and monocytes by incubating supernatants from activated or resting platelets with tumor cells or monocytes, and by bringing resting or activated platelets into close apposition with tumor cell monolayers. CD40L was present on the surface of activated (but not resting) platelets and was also released following platelet activation. Both recombinant soluble CD40L (rsCD40L) and activated platelet supernatants increased procoagulant activity (PCA) and TF antigen in tumor cells and monocytes. The increase in TF activity induced by both rsCD40L and activated platelet supernatants was inhibited by anti-CD40L antibody. Furthermore, contact of activated platelets with tumor cells increased cellular PCA, and this effect was also inhibited by anti-CD40L. In malignancy, the increase in cellular TF activity via CD40 (tumor cell)-CD40L (platelet) interaction may possibly enhance intravascular coagulation and hematogenous metastasis.

Blood Coagulation↗
PubMed2001

Tonsillotomy in children with tonsillar hypertrophy.

Tonsillectomy is one of the most frequent surgical procedures carried out on children. Obstructive sleep apnea syndrome, caused by tonsillar hypertrophy, has been attracting increasing interest and tonsillectomy is often performed as a result of this indication. Regardless of the indication, the main aim of tonsillectomy has always been to remove the tonsils completely. The present study was undertaken in order to investigate the effect of two different surgical techniques, tonsillectomy and tonsillotomy, on clinical symptoms in children with symptoms of obstructive sleep apnea syndrome due to tonsillar hypertophy. The study was conducted as a prospective, randomized trial comparing the clinical effects of standard tonsillectomy and tonsillotomy using a CO2 laser. Forty-three children aged 2-9 years were included. Both groups of patients experienced comparable relief from symptoms of snoring and apneas at follow-up after 3 months and 2 years. There was no significant statistical difference between the two groups of patients in terms of both short- and long-term effects on clinical symptoms. Tonsillotomy caused no measurable bleeding during surgery. Postoperative pain and distress were less pronounced in the tonsillotomy group according to visual analog scale evaluations made by patients, parents and nursing staff. In conclusion tonsillotomy appears to be the less traumatic surgical method in cases of upper airway obstruction in children caused by tonsillar hypertrophy.

Child↗
PubMed2001

Hemoglobin enhances tissue factor expression on human malignant cells.

Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

Carcinoma, Transitional Cell↗
PubMed2001

Purification and properties of human melanoma cell tissue factor.

Tissue factor (TF) is a transmembrane glycoprotein that acts as a receptor for nonactivated and activated factor VII (FVII) and triggers the coagulation cascade. TF plays an important role in hemostasis, but may also have noncoagulation functions in vascular development, angiogenesis, and tumor cell metastasis. In tumor cells, analysis of the role of TF has been hampered by the lack of purified TF. In this study, TF antigen was identified on human A375 malignant melanoma cells using flow cytometry. We further purified TF apoprotein 2,000-fold to homogeneity from A375 melanoma cells using immunoaffinity chromatography. On SDS-polyacrylamide gel electrophoresis under reduction, purified TF apoprotein gave two major protein bands corresponding to molecular weights of 53 and 34 to 36 KD. The identity of these forms of TF was confirmed by Western blotting using a polyclonal antibody against human brain TF. Under reduction, the TF antibody bound with a monomeric form of TF (53 KD), and without reduction, to several forms of TF (34 to 128 KD). Preliminary carbohydrate analysis suggested that TF is a glycoprotein and contains about 22% total carbohydrates. The coagulant activity of the purified apoprotein was reconstituted by the addition of phospholipids. The effects of varying concentrations (0 to 8 microg) of polyclonal antibodies to TF and FVII on TF procoagulant activity were studied. Both antibodies inhibited more than 70% of the procoagulant activity of TF in an FX activation assay. The complex formation between purified TF apoprotein and FVIIa was demonstrated by using an enzyme-linked immunosorbent assay. TF formed a complex with FVIIa in a concentration-dependent and saturable manner. We conclude that in human melanoma cells, TF occurs in monomeric and heterodimeric forms and appears to have similar properties as reported for TF from other sources.

Antibodies↗
PubMed2001

Lack of CYP3A4 inhibition by grapefruit juice and ketoconazole upon clozapine administration in vivo.

The drug-food and drug-drug interaction between grapefruit juice (GFJ) and ketoconazole (KETO) was evaluated in schizophrenic patients given a single dose of clozapine (CLZ). CLZ is metabolized primarily by CYP isozymes 3A4 and 1A2 to two principal metabolites, desmethylclozapine (DCLZ) and clozapine N-oxide (CNO). GFJ and KETO are well known potent CYP 3A4 inhibitors in the gastrointestinal tract and hepatic isozymes, respectively. Twenty-one schizophrenic patients participated in the co-administration of CLZ 50 mg and GFJ. After a one-week washout, five patients were given double the GFJ (HGFJ) dose for 7 consecutive days. In another group of five patients, ketoconazole (KETO) 400 mg was given for 7 consecutive days. At the end of the 7-day period for both groups, CLZ was coadministered with the HGFJ and KETO groups. CLZ, DCLZ and CNO were assayed by HPLC. GFJ, HGJF and ketoconazole failed to significantly change CLZ disposition. Metabolites DCLZ and CNO concentrations remained unchanged during the study. The only exception was decreased Cmax in DCLZ and CNO concentrations. These results indicate that CYP 3A4 inhibition may not be clinically significant compared to CYP 1A2, as previous studies show a dramatic increase in CLZ plasma concentrations with fluvoxamine (CYP 1A2 inhibitor). The reasons for the lack of drug-food and drug-drug interactions with CLZ and CYP 3A4 inhibitors can be explained by the higher Ki values for gastrointestinal and hepatic CYP 3A4 isozymes.

Adult↗
PubMed1999

Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells.

Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in MHC tetramer-binding cells and cytotoxic T cells after DC vaccination. These data provide the first controlled evidence of the immunogenicity of DCs in humans, and demonstrate that a single injection of mature DCs rapidly expands T-cell immunity.

Adolescent↗
PubMed1999

Exposure limits of women in hot environment.

The tolerance of six women to work in hot environments was examined under four environmental conditions from 38 to 44 degrees C dry bulb temperature and 50 to 80 per cent relative humidity, i.e., 32 to 36.5 degrees C effective temperature [ET (normal scale)] in a climatic chamber. The subjects performed bicycle ergometric work at an intensity of 50 W and the exposure duration was determined by the cardiorespiratory, body temperature and sweating responses. At the limit of tolerance, the body core temperature (Tcr) reached over 38.5 degrees C and the heart rates attained a peak level (i.e., about 172 beats/min). The total oxygen demand decreased significantly with higher environmental load, particularly beyond 33.5 degrees C ET (N). While the tolerance time decrement was evident with the higher heat stress, on an average, an increase or decrease of every liter of total oxygen demand was equivalent to a 0.8 min change in the tolerance time. As such, the women volunteers were not susceptible to heat; only in extreme hot situations beyond 33.5 degrees C ET (N), they had unacceptable levels of physiological and psychophysical reactions. Based on the distribution of tolerance time of the women in different exposure conditions, the safe exposure times were estimated, which varied from 43 min [32.0 degrees C ET (N)] to 16 min [36.5 degrees C ET (N)].

Adult↗
PubMed1998

Efficacy of a water-cooled garment for auxiliary body cooling in heat.

The efficacy of a water-cooled jacket for auxiliary body cooling was examined under a simulated hot environment. The personal garment comprised of a water re-circulating three-layered vest of cotton fabric lined with 2 mm diameter latex tubing and inter-spaced coating of rubberized solution. Four subjects wearing the water-cooled jacket were tested in the environment chamber (30, 35 and 40 degrees C DB, 50-60% RH, air velocity 0.3, 0.6 and 0.9 m/s, with corresponding average effective temperature of 26 +/- 2.3, 33 +/- 1.1 and 36 +/- 1.5 degrees C). The inlet water temperature was maintained at 10-12 degrees C, with flow rates of 2.6 +/- 0.3, 4.3 +/- 0.3 and 5.1 +/- 0.3 l/h). At 30 degrees C DB, variation in water flow had marginal effect on microclimate, while at higher temperatures (35 and 40 degrees C DB), the re-circulating cooled water had noticeable effects in lowering microclimate, trunk and other skin temperatures, and maintaining the body core within 36.7 +/- 0.2 to 37.5 +/- 0.2 degrees C, over 2 h exposure at 35 and 40 degrees C DB. The observation indicates that the water-cooled jacket provided auxiliary cooling to maintain comfortable microclimate, skin and body core temperatures. This enabled subjects to sustain comfortable heat balance over 2 h heat exposure without any noticeable heat strain.

Adult↗
PubMed1997

Human heat tolerance in simulated environment.

The heat tolerance of 11 male volunteers were examined under seven climatic conditions in a climatic chamber. The conditions were 38 to 49 degrees C dry bulb temperature and 45 to 80 per cent relative humidity, i.e., 32.3 to 40 degrees C effective temperature-basic [ET(B)]. The ET(B) values were equated to other heat stress indices, e.g., WBGT (Wet-bulb Globe Temperature Index) and Oxford Index. The subjects did ergometric work at an intensity of 60 per cent VO2max. The exposure durations were decided by the cardiorespiratory, body temperature and sweating responses. Of the climatic conditions studied, at 35.4, 38, 39 and 40 degrees C ET(B), the body core temperature (Tcr) reached over 39 degrees C and heart rates attained 172 to 182 beats/min, which were taken as the tolerance limit. The total oxygen demand significantly varied with the increase in environmental warmth, i.e., increase or decrease of one litre of oxygen demand was equivalent to one minute change in tolerance time. The volunteers were not susceptible to heat; only in extreme hot situations beyond 35.4 degrees C ET(B), were unacceptable levels of physiological and psychophysical reactions seen. The study suggests the acceptable and tolerable limits for human exposure in heat: (i) acceptable at 38 to 38.2 degrees C Tcr for a tolerance time of 80 to 85 min; and (ii) the tolerable limit of short duration (40-45 min) at 39 degrees C Tcr that corresponded to 31.5 and 36.5 degrees C ET(B).

Adolescent↗
PubMed1996

Human work capacity under combined stress of work and heat.

The working capacity of young, healthy, unacclimatized men (N = 11) was studied under long-duration (8 to 9 days) exposure to combined work and heat (dry and humid). The dry (Gr A, N = 5) and humid (Gr B, N = 6) groups were exposed to 41.3 +/- 0.6 degrees C DB, 40-50% RH and 39.2 +/- 0.6 degrees C DB, 70-80% RH, respectively, for all days of exposure. The experimental protocol was divided into: (i) direct determination of maximal oxygen uptake (VO2max) by stepped increases in bicycle ergometry everyday in the morning in the initial hours before exposure to heat, after which the recovery process of oxygen debt contraction was examined; and (ii) exposure to heat in a climatic chamber for 2 h where the subjects performed two spells of ergometric work (10 to 12 min each) at a relative intensity of 50 +/- 12 to 69 +/- 11% VO2max. The average heat exposure time for Gr A was higher (108 +/- 12 min) as compared to Gr B (95 +/- 10 min), but Gr B sustained a high heat load as reflected from the high deep-body temperature maintained during the exposure. The high body temperature load of Gr B had a significant effect on the cardiorespiratory capacity, indicating an upward trend in VO2max. This was statistically significant (p < 0.05) for the first four days of exposure. Subjects of Gr B had a relatively higher working capacity compared to those in Gr A on all days. The VO2max and analysis of the fractions of oxygen debt contraction (fast and slow component) indicated that the subjects showed a better training/heat acclimatization effect under hot, humid conditions.

Adult↗
PubMed1995

Protein 1a: a major wheat germ agglutinin binding protein on the surface of human granulocytes associated with the cytoskeleton.

Lectin-receptors on leukocyte and endothelial surfaces are becoming more important in the light of increasing evidence which implicates lectin-carbohydrate interactions in diverse physiological phenomena. This study reports the identification of a major 118 kDa granulocyte surface protein, (Protein 1 a) which binds the lectin wheat germ agglutinin (WGA), and is distinctly different from reported WGA binding granulocyte membrane proteins. Protein 1 a has been isolated from the Triton-soluble and Triton-insoluble lysates of normal individuals and patients with Chronic Myeloid Leukemia (CML) using a combination of differential solubilization, lectin affinity, ion exchange chromatography and HPLC. The protein from the detergent lysates of both normal and CML granulocytes has similar pI values, lectin affinities, and hydrophobicity. However, its solubility in Triton is different in the two cell types. In 71% of CML cases examined, Protein 1 a exhibits decreased Triton solubility suggesting its increased association with the cytoskeleton (CSK). Stimulation of normal granulocytes with WGA leads to the translocation of the soluble form of Protein 1 a to the Triton-insoluble fraction. This cytoskeletal recruitment of Protein 1 a is sustained only under conditions of excess WGA and occupied receptor. The CSK disruptive agent dihydrocytochalasin B (H2CB) releases the insoluble form of the receptor into the Triton-soluble fraction. Investigation of a CSK-involving process such as ligand internalization revealed that CML granulocytes exhibit slower kinetics of internalization of fluorescent WGA molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1995

Distribution and origin of the peripheral innervation of rat cervical esophagus.

Several neurotransmitters, neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), galanin, enkephalin, calcitonin-gene related peptide (GGRP), substance P, as well as nitric oxide synthase (NOS), and the noradrenergic marker tyrosine-hydroxylase (TH) were localized by immunocytochemistry in the cervical esophagus of rat. Nerve fibers containing the neuropeptides, NOS, and TH were distributed in the myenteric plexus, around muscle bundles and small blood vessels. Injection of the retrograde tracer True Blue (TB) into the cervical esophagus resulted in the appearance of labeled nerve cell bodies in the superior cervical, the stellate, the nodose, the sphenopalatine, the dorsal root ganglia at levels C2-C7, and in local ganglia close to the thyroid. Most of the TB-labeled nerve cell bodies in the superior cervical ganglia contained NPY. In the stellate ganglion, a few labeled nerve cell bodies contained VIP whereas an additional few cell bodies stored VIP. In local ganglia, the majority of labeled cell bodies contained VIP. In the nodose ganglion and cervical dorsal root ganglia, the majority of the labeled nerve cell bodies stored CGRP. The results indicate that the cervical esophagus has a dense innervation with multiple neurotransmitters emanating from several ganglia. As judged by the pattern of nerve fiber distribution, they may regulate esophageal peristalsis and blood flow, some of them possibly in a cooperative manner.

Amino Acid Oxidoreductases↗
PubMed1994

Right common carotid artery reconstruction after extracorporeal membrane oxygenation: vascular imaging, cerebral circulation, electroencephalographic, and neurodevelopmental correlates to recovery.

OBJECTIVE: Right common carotid artery (RCCA) ligation after extracorporeal membrane oxygenation by venoarterial bypass may contribute to lateralized cerebral injury. Reconstruction of this artery after extracorporeal membrane oxygenation has proved feasible but has not been evaluated for neurologic outcome in any substantial series of infants. METHODS: We evaluated RCCA reconstruction in 47 infants treated with ECMO and compared their cerebrovascular and neuroanatomic imaging findings, electroencephalograms, and developmental outcomes with those of 93 infants who had no reconstruction. SUMMARY RESULTS: Color Doppler blood flow imaging revealed that carotid artery patency was usually obtained after RCCA reconstruction. Right internal carotid and bilateral anterior and middle cerebral arterial blood flow velocities were generally higher, and were more symmetrically distributed in infants with reconstructed RCCA. Electroencephalography did not disclose an increased risk of deterioration or marked abnormalities in infants after reconstruction, nor were neuroimaging findings consistent with an increased number of either focal or generalized abnormalities. Neurodevelopmental follow-up revealed no differences in the incidence of delays between those with a reconstructed RCCA and those with a ligated RCCA during the first year of life. CONCLUSIONS: Reconstruction of the RCCA after extracorporeal membrane oxygenation may facilitate normal distribution of cerebral blood flow through the circle of Willis, and may augment both left and right middle cerebral artery blood flow immediately after decannulation. The long-term consequences of either ligation or reconstruction of the RCCA will require careful scrutiny, however, before either course is recommended routinely.

Blood Flow Velocity↗
PubMed1994

Triglyceride and coronary heart disease.

The predictive association of triglyceride (TG) in coronary heart disease (CHD). In patients without CHD levels were elevated in those coronary risk factors, as compared to those without the risk factor the elevation of TG may occur in asymptomatic subjects before the onset of clinical manifestation of CHD. The high-risk, asymptomatic subjects with high levels of TG may be on the "threshold" of the sysptomatic phase of CHD. The levels had a positive correlation with body mass index and increased with increasing number of coronary risk factors.

Adult↗
PubMed1992

Helospectin-like immunoreactivity in the esophagus.

Helospectin I and II are two non-amidated, VIP-like peptides, isolated from the salivary gland venom of the lizard Heloderma horridum. The lower esophagus of cat, sheep and man was analyzed for helospectin-like immunoreactivity. Immunocytochemistry revealed helospectin-immunoreactive nerve fibers in the muscle layers, submucosa and mucosa of all species studied. In myenteric ganglia helospectin-immunoreactive nerve fibers and nerve cell bodies could be seen. Double immunostaining for helospectin and vasoactive intestinal peptide (VIP) revealed their coexistence in nerve fibers and cell bodies throughout the lower esophagus of all species tested. Double immunostaining for helospectin and neuropeptide Y revealed their coexistence in nerve fibres surrounding vascular and non-vascular smooth muscle. In the cat and sheep (but not in man) a subpopulation of the helospectin/VIP-containing fibers stored, in addition, substance P. The helospectin-immunoreactive material in the esophagus probably constitutes a novel neuropeptide. The distribution of the VIP/helospectin-immunoreactive neurons and fibers indicates their possible involvement in the regulation of motor and secretory activities.

Animals↗
PubMed1992

Differential phosphorylation--cause for defective internalization of aggregated IgG by chronic myeloid leukemic granulocytes?

Granulocytes from the peripheral blood of patients with chronic myeloid leukemia (CML) are known to exhibit a defect in internalization of aggregated IgG relative to normal cells. As this aberration may arise due to defective transmembrane signalling, this study was undertaken to analyze alterations, if any, in protein phosphorylation between the two cell types. Normal and CML granulocytes were labeled with 32P-sodium orthophosphate and then stimulated with aggregated IgG. The phosphoproteins in the unstimulated and stimulated cells were analyzed by 2D-SDS-PAGE followed by autoradiography. The results show that there are five distinctly identifiable, reproducibly phosphorylated proteins referred to as Pp1-Pp5. In the unstimulated normal cells, Pp1 is less phosphorylated than Pp3, while in CML cells, Pp1 is more intense than Pp3. On stimulation of normal cells, with aggregated IgG, intensity of Pp1 increases while that of Pp3 decreases. In CML cells this response is reversed. We conclude that one of the causes for the defective internalization of IgG by CML granulocytes may probably be the observed differences in the phosphorylation of the proteins under study.

Granulocytes↗