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Biomedical subjects

D Gupta

Publications and source records attributed to D Gupta.

At least 19 recordsLinked to original sources

Thermodynamic and kinetic studies on the mechanism of binding of methylumbelliferyl glycosides to jacalin.

The binding of Artocarpus integrifolia lectin (jacalin) to 4-methylumbelliferyl (Meumb)-glycosides, Gal alpha Meumb, Gal beta Meumb, GalNAc alpha Meumb, GalNAc beta-Meumb, and Gal beta 3GalNAc beta Meumb was examined by extrinsic fluorescence quenching titration and stopped flow spectrofluorimetry. The binding was characterized by 100% quenching of fluorescence of Meumb-glycosides. Their association constants range from 2.0 x 10(4) to 1.58 x 10(6) M-1 at 15 degrees C. Entropic contribution is the major stabilizing force for avid binding of Meumb-glycosides indicating the existence of a hydrophobic site that is complementary to their methylumbelliferyl group. The second order association rate constants for interaction of these sugars with lectin at 15 degrees C vary from 8.8 x 10(5) to 3.24 x 10(6) M-1 S-1, at pH 7.2. The first order dissociation rate constants range from 2.30 to 43.0 S-1 at 15 degrees C. Despite the differences in their association rate constants, the overall values of association constants for these saccharides are determined by their dissociation rate constants. The second order rate constant for the association of Meumb-glycosides follows a pattern consistent with the magnitude of the activation energies involved therin. Activation parameters for association of all ligands illustrate that the origin of the barrier between binding of jacalin to Meumb-glycosides is entropic, and the enthalpic contribution is small. A correlation between these parameters and the structure of the ligands on the association rates underscores the importance of steric factors in determining protein saccharide recognitions.

Binding, Competitive

Response of CFU-GM (colony forming units for granulocytes and macrophages) from intact and pinealectomized rat bone marrow to murine recombinant interleukin-3 (rIl-3), recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) and human recombinant erythropoietin (rEPO).

The present study provides evidence, for the first time, of a role of the pineal gland in the proliferation of CFU-GM under the influence of different cytokines. The degree of colony formation in different cytokine groups was evaluated after 24 h, 3, 7 and 10 days. The colony growth in the present type of bone marrow cell cultures slows after the 10th day and ceases after the 14th day of incubation. The results show that rGM-CSF and the combination of rGM-CSF with rIl-3 and with rEPO stimulate the colony formation of granulocytes and macrophages. A 50% general reduction in the colony number was noted in the pinealectomy group. Their pattern of response to the different cytokines was similar to that of the intact group. It is suggested that the pineal activity has a physiological role in important aspects of host defence mechanisms, such as the proliferation of CFU-GM.

Animals

Effect of the pineal gland on circadian rhythmicity of colony forming units for granulocytes and macrophages (CFU-GM) from rat bone marrow cell cultures.

The present study provides evidence that the pineal gland has a physiological role in the proliferation of colony forming units for granulocytes and macrophages (CFU-GM). A biphasic circadian rhythm of CFU-GM proliferation in rat bone marrow cell cultures (BMC) from intact animals peaking at 0600 and 1800 was observed. Pinealectomy (Px) at 1600 obliterated the circadian rhythm patterns of CFU-GM. Afternoon injections of melatonin (1630, 20 micrograms/per day for 10 days) to Px animals restored the rhythmicity. When pinealectomy was done at 0800, the morning peak remained unaltered and the colony number at 1800 was higher than that found in the afternoon Px animals. In conclusion, the pineal gland or its main hormone melatonin seems to have a regulatory role in the proliferation of CFU-GM in rat BMC. Further, the expression of the activity of CFU-GM in rat BMC depends on the time when pinealectomy is done or melatonin is substituted.

Animals

Diltiazem as adjunctive oral therapy in patients with chronic atrial fibrillation.

Digoxin frequently fails to control the heart rate in patients of chronic atrial fibrillation particularly during exertion. We have studied in 20 such patients the effect of adding diltiazem (180 mg/day) on resting and peak exercise heart rates. An attempt was also made to determine its effects on exercise tolerance by using treadmill and 6 minute walk test. Addition of diltiazem resulted in significant attenuation of heart rate both at rest and at peak exercise. The resting and exercise mean heart rates on digoxin alone were 98.9 +/- 21.5 b.p.m. and 160.2 +/- 35.68 b.p.m. respectively. After diltiazem this reduced to 78.7 +/- 12.30 b.p.m. at rest and 132.4 +/- 40.4 b.p.m. at peak exercise (p < 0.01). There was no significant effect on exercise tolerance. In conclusion, the addition of diltiazem substantially reduced the excessive heart rate response to exercise in digitalised patients of chronic atrial fibrillation.

Administration, Oral

Evaluation of haemotherapy in thalassaemias (20 years of Indian experience).

Two hundred fifty-one patients of beta-thalassaemia ranging from 3 months to 15 years of age were evaluated. They were maintained on hypertransfusion regimen and received periodic transfusions of group specific packed red cells. These multiple transfused patients were subjected to the tests for detection of transfusion malaria, HBsAg and allo-antibodies against red cells. Malaria infection and HBsAg were detected in 6.4% and 15.5% of patients respectively, while allo-antibodies were detected in 15.5% of patients. Thirteen patients (5.18%) developed hypersplenism and associated pressure symptoms due to splenomegaly for which they underwent splenectomy. Postsplenectomy period was uneventful and showed marked decrease in the frequency and quantitative requirements of transfusions and overall improvement in health. The continuing steady improvement of the prognosis in thalassaemia secondary to hypertransfusion regimen required us to transfer attention to other problems involved in thalassaemia management such as problems of hypersplenism and problems of multiple transfusion.

Adolescent

Further characterization of the saccharide specificity of peanut (Arachis hypogaea) agglutinin.

2-Dansylamino-2-deoxy-D-galactose (GalNDns) has been shown to bind to peanut (Arachis hypogaea) agglutinin (PNA) in a saccharide-specific manner. This binding was accompanied by a five-fold increase in the fluorescence of GalNDns. The interaction was characterized by an association constant of 0.15 mM at 15 degrees and delta H and delta S values of -57.04 kJ.mol-1 and -118.1J.mol-1.K-1, respectively. Binding of a variety of other mono-, di- and oligo-saccharides to PNA, studied by monitoring their ability to dissociate the PNA GalNDns complex, revealed that PNA interacts with several T-antigen-related structures, such as beta-D-Galp-(1----3)-D-GalNAc, beta-D-Galp-(1----3)-alpha-D-GalpNAcOMe, and beta-D-Galp-(1----3)-alpha-D-GalpNAc-(1----3)-Ser, as well as the asialo-GM1 tetrasaccharide, with comparable affinity, thus showing that this lectin does not discriminate between saccharides in which the penultimate sugar of the beta-D-Galp-(1----3)-D-GalNAc unit is the alpha or beta anomer, in contrast to jacalin (Artocarpus integrifolia agglutinin), another anti T-lectin which preferentially binds to beta-D-Galp-(1----3)-alpha-D-GalNAc and does not recognize beta-D-Galp-(1----3)-beta-D-GalNAc or the related asialo-GM1 oligosaccharide. These studies also indicated that, in the extended combining region of PNA which accommodates a disaccharide, the primary subsite (subsite A) is highly specific for D-galactose, whereas the secondary subsite (subsite B) is less specific and can accommodate various structures, such as D-galactose, 2-acetamido-2-deoxy-D-galactose, D-glucose, and 2-acetamido-2-deoxy-D-glucose.

Arachis

Elevated prolactin levels in human aqueous humor of patients with anterior uveitis.

Evidence is accumulating that prolactin (PRL) may play a physiological role in the regulation of humoral and cell-mediated immune responses. On the basis of these observations, we measured levels in the serum and aqueous humor of 28 patients with cataract or anterior uveitis with concomitant cataract. Intraocular concentrations were measured in a range from 0.1 to 3.4 ng/ml. Whereas serum PRL levels failed to show significant differences between the two groups (P = 0.39), intraocular concentrations were significantly higher in uveitis patients (P less than 0.001). The level in aqueous humor did not reflect the serum concentration in either group. To the best of our knowledge, this is the first study measuring PRL concentrations in human aqueous humor.

Adolescent

Flavonoid glycosides from Cassia alata.

Two new glycosides, chrysoeriol-7-O-(2"-O-beta-D-mannopyranosyl)-beta-D-allopyranos ide and rhamnetin-3-O-(2"-O-beta-D-mannopyranosyl)-beta-D-allopyranosid e, were isolated from the seeds of Cassia alata. The structures were established on the basis of chemical evidence and spectroscopic methods, especially NMR.

Carbohydrate Sequence

Lung transfer components in hyperthyroidism.

Pulmonary functions were studied in twenty hyperthyroid non smoker patients. Their FVC, PEFR and MVV were significantly lowered while FEV1/FVC% and EFR25-75% were normal. Amongst the diffusion functions, Tlco, Dm and VA were reduced and VC increased, though these changes were not statistically significant. After the achievement of euthyroid state, statistically significant increase was seen in FVC, PEFR, MVV, Tlco120, Dm and VA with significant decrease in Vc from the basal levels. FEV1/FVC% and EFR25-75% were not affected. These observations suggest that the principal abnormalities in pulmonary functions in the hyperthyroid state are increased pulmonary capillary blood volume and respiratory myopathy, which are reversed as euthyroid state is achieved.

Adult

Tumor-inhibiting activity in the rat pineal gland displays a circannual rhythm.

The aim of this study was to investigate whether the tumor-inhibiting activity present in the rat pineal gland undergoes seasonal fluctuations as do other pineal substances. Crude ethanol extracts of rat pineal glands were tested for tumor-inhibiting activity in an in vitro microbioassay using human erythroleukemia cells which could not be inhibited by melatonin. Highest activity was detected in summer and least inhibition and even stimulation were observed in winter. There were no differences in activity between animals of different age, sex, or strain. Therefore, season seems to be the factor that exerts the most important influence on the content of tumor-inhibiting activity in the rat pineal gland. Correlation with seasonality in the occurrence of cancer is discussed.

Animals

Sex- and age-dependent nature of the cytoplasmic 5 alpha-dihydrotestosterone (DHT) binding site/receptor in bovine pineal gland.

Recent research has justified the presumption that the pineal gland plays a role in the regulation of the gonadal system in mammals. Evidence also exists for androgen receptors in pinealocytes. In the current study, our approach has been to assess the age- and sex-dependent nature of 5 alpha-DHT receptors in bovine pineal. Although no significant difference was noted between various groups of bulls, cows, peripuberal cows, and calves (male) for pineal weight, the cytoplasmic 5 alpha-DHT binding site/receptor content in the pineal gland differed significantly. While the males had a low androgen receptor concentration in the pineal (46 fmol/pineal), the females showed the highest (442 fmol/pineal). The peripuberal females without calves and calves (male) presented a 5 alpha-DHT receptor content in between (225 fmol/pineal; 138 fmol/pineal). When the data were related to unit weight of pineal tissue, the difference still existed. It is suggested that the concentration of cytoplasmic 5 alpha-DHT receptors reflects the cellular activity and they are inversely related. Further, low cytoplasmic receptors also indicate that most of it is confined to the nuclear sites, as generally suggested for other androgen-dependent tissues. In the light of these suggestions, it is possible that lowest cytosolic 5 alpha-DHT receptor concentration in the males, in reality, reflects a higher degree of cellular function and a high concentration of the receptors in the nuclear site. Similarly, the peripuberal cows and calves perhaps have more cellular activity in the pineal than the mature cows. The current investigation, for the first time, by directly estimating the androgen receptors/binding site in the bovine pineal gland, demonstrates the sex- and age-dependent nature.

Aging

Effect of the mammary carcinogen 7,12-dimethylbenz[a]anthracene on pineal melatonin biosynthesis, secretion and peripheral metabolism.

The aim of this study was to establish whether the nocturnal peak concentrations of circulating melatonin are affected by a single dose of 7,12-dimethylbenz[a]anthracene (DMBA) in female Sprague-Dawley rats as used for mammary tumor induction. Prior to this, the circadian rhythms of melatonin (N-acetyl-5-methoxytryptamine) and 6-sulfatoxymelatonin, the main metabolic product of melatonin, were determined in female Sprague-Dawley rats. The cosinor analysis revealed significant circadian rhythms with very similar acrophases around 1.00 a.m. for both substances. To enable explanations for possible changes in plasma melatonin after DMBA treatment, the biosynthesis in the pineal and the major metabolic product in the liver, 6-sulfatoxymelatonin, were measured 2 and 7 days after DMBA. Plasma melatonin was depressed by 31-37% (p less than 0.05) 2 and 7 days after DMBA but the pineal melatonin content remained unchanged. 2 days after DMBA, pineal serotonin and N-acetylserotonin showed a transient elevation of 35% (p less than 0.025) and 25% (p less than 0.05), respectively. The plasma concentrations of 6-sulfatoxymelatonin were the same in DMBA- and vehicle-treated animals. An elevation of the 6-sulfatoxymelatonin/melatonin ratio indicated a relative increase in the metabolism of melatonin due to DMBA. The absence of an absolute increase in 6-sulfatoxymelatonin after DMBA could be caused by an additional shift within the spectrum of different metabolic products of melatonin due to the carcinogen. Possible mechanisms are discussed.

9,10-Dimethyl-1,2-benzanthracene

Osteogenic sarcoma of the frontal sinus.

Occurrence of osteogenic sarcoma in the craniofacial bones is limited. The case presented here is only the second reported case of osteogenic sarcoma of the frontal sinus, occurring in an 80-year-old woman who presented with proptosis and developed neurologic symptoms. The radiographic appearance was of a diffuse opacity with thickening of the calvaria. Tumor tissue was adherent to the dura, and there was a fairly good initial response with the methotrexate sodium-cisplatin combination chemotherapy used, but the outcome was fatal.

Aged

Calcified hypernephroma. A case report.

Pattern of classification in an renal neoplasm is variable. If calcium is located nonperipherally (within the mass) it is more likely to be a renal cell carcinoma. But peripheral calcification does not rule out malignancy.

Adult

Stage-dependent depression of melatonin in patients with primary breast cancer. Correlation with prolactin, thyroid stimulating hormone, and steroid receptors.

Serum melatonin was determined over 24 hours in 35 patients with breast cancer with either a fresh primary tumor (n = 23) or a secondary tumor (n = 12) and in 28 patients with untreated benign breast disease (controls) having a fibroadenoma (n = 10), fibrocystic mastopathy (n = 14), or other breast diseases (n = 4). Circadian rhythms existed in all groups with acrophases at 2 a.m. A 50% depression of peak and amplitude occurred in the group of patients with primary breast cancer compared with age-matched controls (P less than 0.001, P less than 0.01). The peak declined with increasing tumor size: 27% at Stage T1, 53% at T2 (P less than 0.001), and 73% at T3 (P less than 0.05). In contrast, patients with secondary breast cancer, particularly those receiving antiestrogen therapy, had a melatonin peak similar to controls. These results demonstrated a transient depression of pineal melatonin secretion in primary breast cancer and indicated a dynamic role of the pineal gland in malignancy. To investigate some endocrine effects of a depressed melatonin peak, the 24-hour rhythms of prolactin (PRL) and thyroid stimulating hormone (TSH) were determined in patients with primary breast cancer and compared with patients with secondary breast cancer. The PRL had significant circadian rhythms in both groups; but acrophases occurred at midnight in patients with secondary breast cancer, and there were unusually high concentrations at noon in patients with primary breast cancer. Circadian rhythms were not seen for TSH, but the 24-hour average secretion was depressed by 45% (P less than 0.01) in patients with primary breast cancer. The abnormal concentrations of PRL and TSH in these patients could be due to a depressed melatonin peak normally serving as a central circadian synchronizer and modulator of the secretion of adenohypophysial hormones. Additionally, a positive correlation existed between the nocturnal melatonin peak and progesterone and androgen receptor concentrations in primary tumors indicating a direct involvement of melatonin in the growth control of breast cancer.

Adult