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S Dutta

Publications and source records attributed to S Dutta.

At least 145 records · Page 8Linked to original sources
PubMed1994

Increased expression of pp60c-src in gastric mucosa of aged rats.

The relationship between proliferative activity and the expression of pp60c-src in gastric mucosa (oxyntic gland area) of young (4-month) and aged (24-month) Fischer 344 rats was examined. Gastric mucosal proliferative activity, as assessed by 5-bromo-2'-deoxyuridine (BrdU) immunoreactive cells, was found to be 115% (p < .001) higher in aged than in young rats. This was associated with a 47% rise (p < .025) in overall tyrosine kinase (Tyr-k) activity and a 5-7-fold increase in autophosphorylation of four prominent protein bands with M(r) of 40, 55, 60, and 70 kDa in gastric mucosal membranes. A similar phenomenon was also observed for Tyr-k activity of pp60c-src in that the aged rats revealed a 69% (p < .025) higher enzyme activity and a 5-fold rise in the extent of autophosphorylation of this protein when compared with the corresponding values from young animals. Increased Tyr-k activity of pp60c-src in the gastric mucosa of aged rats could in part be due to higher levels of this protein because the relative concentration of pp60c-src, as assessed by Western blot analysis, showed a 2-5-fold increase over the young animals. In addition, the relative concentration of c-src mRNA in the gastric mucosa of aged rats was also found to be 5-6-fold higher than in young animals. We suggest that pp60c-src may play a role in regulating gastric mucosal proliferative processes in the gastric mucosa of aged rats.

Aging↗
PubMed1994

Changes in perimicrovascular protein spatial distribution due to superfusate.

OBJECTIVE: To determine superfusate-induced changes in the distribution of plasma proteins in the perimicrovascular interstitial matrix. METHODS: Rats were anesthetized with sodium pentobarbital and a mesenteric loop was exteriorized. Intravital video microspectrophotometry was performed using wavelengths of 280, 320, and 700 nm. The images were analyzed to give protein and collagen spatial distributions in vascular regions of rat mesenteric tissue. Perimicrovascular protein concentrations were fitted to an exponential decay model ci + cr exp (-x/k), where ci is distal protein concentration, ci + cr is the protein concentration proximal to the vessel, x is the distance from the vessel wall, and k is the decay constant indicating protein gradient slope. RESULTS: Before superfusion with 0.5-ml normal saline, ci = 1.45 +/- 0.13 g/dl, ci + cr = 4.56 +/- 0.23 g/dl. After the first superfusion, ci decreased (p < 0.01) to 0.53 +/- 0.06 g/dl; following a second superfusion, cr decreased to 0.4 +/- 0.03 g/dl; an additional final superfusion caused a further decrease to 0.33 +/- 0.02 g/dl. ci + cr also decreased significantly during repeated superfusions to 2.92 +/- 0.15, 2.35 +/- 0.25, and 2.1 +/- 0.12 g/dl, respectively. CONCLUSIONS: Superfusion produced changes in perivascular and distal interstitial matrix protein distribution. Protein concentration proximal to the microvessel remained higher than distal concentrations. This could be due to increased gel concentrations inhibiting protein mobility.

Animals↗
PubMed1994

Emerging facets of diastolic heart failure.

One hundred patients with congestive cardiac failure (52 males and 48 females) with age ranging from 16 to 56 yrs (mean age 42 +/- 6) were studied to determine the relative prevalence of systolic and diastolic failures, their clinical profiles and common aetiologies. Age matched 25 control subjects were also studied to established a normal range of echocardiographic values for LV diastolic function. Thirty eight patients (38%) were found to have pure diastolic heart failure and another 5 (5%) and 57 (57%) were detected to have mixed and systolic failures respectively. An attempt to correlate the clinical assessment of diastolic failure with echo doppler study showed the sensitivity and specificity of the clinical criteria for diagnosis of diastolic heart failure to be 100% and 91.94% respectively. Of the 38 cases of diastolic failure detected 39.5% had hypertension, 31.6% ischaemic heart disease and 13.16% hypertrophic cardiomyopathy.

Adolescent↗
PubMed1994

Aging diminishes gastric mucosal regeneration: relationship to tyrosine kinases.

BACKGROUND: Increased incidence of gastric ulcer observed in the aged could be partly attributed to increased susceptibility of the mucosa to various damaging agents together with impediment of the repair process. The present investigation was undertaken to compare the rate of mucosal regeneration and the role of tyrosine kinases in regulation of this process between young (4-month-old) and aged (24-month-old) rats during the first 24 hours after injury. EXPERIMENTAL DESIGN: Groups of young and aged rats were given intragastrically with either 2 M NaCl (1.5 ml/130 gm body weight), or an equivalent volume of water and killed 1, 6, and 24 hours later. Each animal was injected intraperitoneally with 5-bromo-2'-deoxyuridine (BrdU; 50 mg/kg) 1 hour before killing to assess proliferative activity by immunocytochemistry. The stomach (oxyntic gland area) was also evaluated by light microscopy for the extent of injury and subsequent regeneration, and mucosa assayed for ornithine decarboxylase and tyrosine kinase (Tyr-k) activity and tyrosine phosphorylation of membrane proteins. RESULTS: Although 2 M NaCl caused extensive damage to the gastric mucosa in both young and aged rats, as evidenced by the total loss of the surface epithelium at 1 hour postinjury, the degree of regeneration was faster in young animals. In young rats, gastric epithelium showed signs of regeneration at 6 hours postinjury and was essentially complete by 24 hours. In contrast, in aged rats, only intermittent surface cells were seen 24 hours after injury. In both age groups, injury resulted in stimulation of mucosal proliferative activity. However, whereas ornithine decarboxylase activity in both age groups was maximally stimulated (350% in young versus 80% in aged) at 6 hours after injury, the number of BrdU-positive cells in young rats increased steadily with time after injury. In contrast, aged rats showed a biphasic pattern in that the number of BrdU-positive cells/gland remained decreased for up to 6 hours, whereafter a steep rise occurred. At 24 hours after injury, the number of BrdU-positive cells/gastric gland in aged rats were found to be higher than in young rats (6 +/- 1.5 cells/gland in young rats versus 9 +/- 2.1 cells/gland in aged rats). The pattern of Tyr-k activity in young and aged rats after injury was found to be quite different from that observed for proliferative activity. In young rats, mucosal Tyr-k activity increased by about 60% at 1 hour after injury, then decreased slightly over the next 5 hours and increased again revealing a 120% rise at 24 hours postinjury. This was associated with a concomitant change in tyrosine phosphorylation of six membrane proteins with molecular weight (in kilodalton) of 30, 35, 50, 55, 60 and 70. In contrast, in aged rats, Tyr-k activity was increased only marginally (about 20%) during the first 6 hours, but at 24 hours postinjury it was found to be 70% above the control. In aged rats, injury produced no significant stimulation in tyrosine phosphorylation of gastric mucosal membrane proteins. CONCLUSIONS: We conclude that aging is associated with the diminished regenerative capacity of the gastric mucosa. This could partly be attributed to diminished activation of mucosal Tyr-k and decreased tyrosine phosphorylation of certain membrane proteins.

Aged↗
PubMed1993

Functions of interleukin-8 are mediated through thiol group(s) of IL-8 receptor in human polymorphonuclear neutrophils. Effects of 5,5'-dithio-bis(2-nitrobenzoic acid) on IL-8 receptor.

Interleukin-8, a neutrophil chemotactic agent causes excessive accumulation of the cells in a number of inflammatory diseases. The activity has been shown to be mediated through a specific functional receptor present on the surface of neutrophils. No information is available about the amino acids constituting the IL-8 binding domain of the receptor. Treatment of neutrophils with 5,5'-dithio-bis(2-nitrobenzoic acid), a thiol-specific modifier, at the concentrations of 0.4 mM and 1 mM reduced IL-8 binding ability and IL-8-induced migration of the cells by 45% and 65%, respectively. Dithiothreitol could regenerate the binding capacity and the ligand could protect the receptor from the effect of the reagent. All the evidence suggests that one or more critical thiol residues are located in the IL-8 binding site of the receptor which are indispensible for normal functions of IL-8.

Chemotaxis↗
PubMed1993

Evaluation of 'cypenhymustine', a new anticancer compound, in murine tumour models.

'Cypenhymustine', 3-[2-[bis(2'-chloroethyl)-amino] ethyl]-5,5- tetramethylenehydantoin, has been synthesised as a potential analog of spiromustine (NSC 172112). The LD50 value was determined in Swiss male mice and found to be 65.0 mg/kg by single i.p. injection. In in vivo screening experiments, three parameters, namely, ascites cell count, ascites fluid measurement and increase in life span (ILS) of drug-treated over control Swiss mice were studied in three murine ascites tumours namely Ehrlich ascites carcinoma (EAC), sarcoma-180 (S-180) and Dalton's lymphoma (DL). Cypenhymustine exhibited a very high percentage of inhibition of both the ascites cell and fluid in these models and also displayed excellent reproducible ILS activity (ILS values of 151 in EAC, 157 in S-180 and 181 in DL at the optimum dose of 3 mg/kg for days 1-7 treatment following tumour transplant on day 0) having a 'curative' effect (1-2 animals: 6 having > 60 days survival rate). The chemical alkylating activity has been compared with spiromustine and another antitumour agent namely nor-HN2.

Animals↗
PubMed1993

Modification of sulfhydryl groups of interleukin-8 (IL-8) receptor impairs binding of IL-8 and IL-8-mediated chemotactic response of human polymorphonuclear neutrophils.

Interleukin-8 (IL-8), a monocyte-derived neutrophil chemotactic agent, has a potential role in the regulation of inflammatory responses. The specific receptor for IL-8 has been identified and characterized on the surface of human neutrophils (Samanta, A. K., Oppenheim, J. J., and Matsushima, K. (1989) J. Exp. Med. 169, 1185-1189). The present study demonstrates that at least two sulfhydryl groups of this receptor from human neutrophils participate in the binding of IL-8. Incubation of neutrophils with sulfhydryl group-modifying reagents, N-ethylmaleimide and diazene dicarboxylic acid bis-N,N-dimethylamide (diamide), severely impaired the binding of 125I-IL-8 to neutrophils. Treatment with 0.8 mM N-ethylmaleimide and 0.4 mM diamide inhibit binding of 125I-IL-8 to the neutrophils by 62 and 60%, respectively. These inhibitory effects could be reversed by 84-87% by treatment with 2-4 mM dithiothreitol. The saturable amount of the ligand, IL-8, provided partial protection against the modifying reagents. N-Ethylmaleimide and diamide at a concentration of 0.4 mM reduced chemotactic migration of neutrophils in a Boyden chamber by 95 and 60%, respectively. At a concentration of 0.4 mM, N-ethylmaleimide reduced the IL-8-induced (10 micrograms/ml) release of myeloperoxidase by 50%. Under identical conditions, 0.4 mM diamide could reduce release of myeloperoxidase by 63%. Finally, N-ethylmaleimide severely affected the overall binding and total uptake of 125I-IL-8 to the neutrophils at 37 degrees C, a condition required for receptor-mediated internalization of the ligand and recycling of the receptor to the surface of neutrophils. Nitro blue tetrazolium reduction test of the lipopolysaccharide-stimulated neutrophils indicates that compared to control general metabolic functions of thiol-modified cells were markedly retained. These data suggest that at least two conformationally vicinal free reactive sulfhydryl groups are located in the binding domain of the receptor in neutrophils which are essential for IL-8-mediated biological responses.

Binding Sites↗
PubMed1993

Computerized data acquisition and analysis applied to chemiluminescence detection of nitric oxide in headspace gas.

Nitric oxide (NO) is an important messenger molecule which is implicated in an ever increasing number of physiological, pharmacological, and pathological processes. Quantitative and qualitative analysis of NO has been hindered by its extremely short half-life in biological systems, and thus there is a keen interest in developing accurate techniques to measure NO. We have employed a modification of the chemiluminescence NO detection technique used by J.F. Brien et al. (J Pharmacol Methods 1991;25:19-27) to measure the photo-induced release of NO from several structurally unrelated drugs including streptozotocin (STZ) and sodium nitroprusside (SNP). We were unable to calibrate the instrument by measuring peak heights from an attached chart recorder in response to increasing amounts of injected nitric oxide. The extremely fast rise times of peaks from the chemiluminescence detector exceeded the capacity of the pen-servomotor mechanism of the chart recorder to accurately measure nitric oxide response curves. We, therefore, digitized the detector's output with an analog-to-digital convertor board connected to an IBM PC. The signal was acquired and analyzed by a program called NOXIDE. Using the NOXIDE program we were able to accurately measure both the peak height and total integrated area of each peak and show that the area, but not peak height, correlates extremely well (r = 0.9991) with standard injections of 20.0-750.0 pmol NO.

Calibration↗
PubMed1993

Sustained local anesthetic release from bioerodible polymer matrices: a potential method for prolonged regional anesthesia.

Polyanhydride polymer matrices have been used successfully for sustained release of a number of drugs in vitro and in vivo. Dibucaine free base, dibucaine HCl, and bupivacaine HCl were incorporated into polymer matrices with copolymer 1,3-bis(p-carboxyphenoxy)propane-sebacic acid anhydride (1:4). Drug release was measured in vitro following incubation of the drug-polymer matrices in phosphate buffered solution, pH 7.4, at 37 degrees C, to approximate in vivo conditions. Local anesthetics were released in a sustained manner yielding 90% cumulative drug release over periods ranging from 3 to 14 days. The kinetics of release varied with both the choice of local anesthetic and the method of drug incorporation into the matrix (hot melt versus compression molding). Polymer local anesthetic matrix devices (PLAM), loaded by hot melt incorporation with 20% bupivacaine, were implanted in vivo adjacent to the sciatic nerve in three rats. Reversible neural blockade was observed for 4 days in all animals. Polymer implants without local anesthetic showed no neural blockade. This technology could lead to methods of prolonged blockade of peripheral nerves or of sympathetic ganglia, which may be utilized for the management of postoperative pain, sympathetically maintained pain, or certain forms of chronic pain.

Analysis of Variance↗
PubMed1993

Pulmonary biophysical effects of triiodothyronine augmentation during sepsis-induced hypothyroidism.

Sepsis may cause pulmonary dysfunction and altered metabolism; triiodothyronine (T3) replacement improves lung function and surfactant pool. We evaluated the biophysical effects of T3 replacement during sepsis-induced hypothyroidism. Male Holtzman rats underwent cecal ligation and puncture (CLP) or sham laparotomy (S); treatment was administered consisting of T3 (3 ng/h) or saline. Twenty-four hours after CLP, lungs were ventilation-perfused with oxygenated N-2-hydroxylpiperazine-N1-2-ethanesulfonic acid (HEPES) with 5 microCi 3-H choline (3-HC) for 1 hour. Perfusion pressures were continuously monitored; perfusate was monitored for 3-HC uptake and oxygen extraction. Triiodothyronine treatment abolished the sepsis-induced decrease in free T3 levels (S = 68 +/- 5 ng/dL, CLP < 15 ng/dL, CLP/T3 = 91 +/- 20 ng/dL). Lung wet-to-dry ratios and vascular and tracheal pressures were maintained by T3 treatment. Choline incorporation was not altered by sepsis or treatment. Triiodothyronine treatment reduced the sepsis-induced increase in oxygen requirement and improved septic pulmonary compromise through a nonhypermetabolic effect.

Animals↗
PubMed1993

Changes in rat mesentery interstitial matrix due to superfusate.

Animal preparations for microscopy often require a superfusate solution to cover surgically exposed tissue. There are few, if any, data concerning the effects of this solution on extravascular protein concentration and hydration. The effect of superfusion on mesenteric tissue in anesthetized male Sprague-Dawley rats was studied. Tissue samples were taken from nonsuperfused and superfused tissue and analyzed for hydration, albumin, and transferrin content. The mesenteric tissue interstitial matrix was rapidly altered by normal saline superfusate. After superfusion, there was a decrease (P < 0.01) in tissue albumin concentration from 1.17 +/- 0.27 to 0.10 +/- 0.08 g/dl (n = 9). Tissue hydration increased from 4.98 +/- 0.8 micrograms water/microgram dry wt in controls to 7.38 +/- 1.2 micrograms water/micrograms dry wt after superfusion. When a range of superfusate albumin concentrations was used (0, 1, 2, and 3 g/dl), tissue albumin concentration changed 0.59 +/- 0.09 g/dl for each gram per deciliter change in superfusate concentration (P < 0.0001). The large changes in interstitial matrix protein content and hydration suggest that superfusate solution effects need to be considered in microvascular protein transport experiments.

Animals↗
PubMed1993

Effects of triiodothyronine (T3) supplementation upon ozone-induced lung injury.

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones; the physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. We demonstrated an increase in metabolic rate and pulmonary injury in lungs from ozone exposed, T3 treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. This suggests that although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.

Animals↗
PubMed1993

Evaluation of 2-(methylaminosulfonyl)-1-(arylsulfonyl)-1-methylhydrazines as anticancer agents.

Seven new 2-(methylaminosulfonyl)-1-(arylsulfonyl)-1-methylhydrazines were prepared. The anticancer activity of these compounds was assessed in murine Ehrlich ascites carcinoma (EAC) by in vivo screening. Moderate in vivo activity in EAC was exhibited by three compounds. All of them were screened in vitro against a battery of human tumor cell lines at the National Cancer Institute (NCI), USA. One of them, compound 3a has displayed highly significant specificity in the renal tumor cell line RXF 393. These three compounds were also assessed for in vitro anti-HIV activity at the NCI, however, they have not reached the criteria of significant activity. The alkylating activity of the compounds was determined by measuring the absorbance of the alkylated product of 4-(4-nitrobenzyl)pyridine. It has been found that they are capable of acting as chemical alkylating agents.

Animals↗