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Biomedical subjects

R Singh

Publications and source records attributed to R Singh.

At least 199 records · Page 11Linked to original sources
PubMed2001

Antiallergic/antiasthmatic effect of novel antiallergic hexapeptide-95/220 in various experimental models.

The effects of newly synthesized antiallergic hexapeptide 95/220 was investigated on various allergic and asthmatic test models. This newly developed peptide was found to be more potent than clinically used drug disodium cromoglycate (DSCG). Hexapeptide 95/220 inhibited immediate hypersensitivity reactions such as passive cutaneous anaphylaxis (PCA) and mast cell degranulation in rats, antigen-induced bronchoconstriction in actively sensitized guinea pigs in dose dependent manner like DSCG. Antigen-induced contraction of guinea pig ileum was also markedly inhibited by this newly developed hexapeptide in the same fashion as ketotifen and DSCG did but at comparatively lower dose. Egg albumin-induced histamine release was also blocked by this hexapeptide from chopped lung tissues of sensitized guinea pigs. These results suggest that hexapeptide' 95/220 has potent inhibitory effect on immediate hypersensitivity reactions thereby inhibiting mediator release from mast cell. Moreover, this newly synthesized peptide is orally active and effective at lower doses as compared to standard drugs.

Animals↗
PubMed2001

Circadian pattern of cardiovascular and cerebrovascular diseases in geriatric population.

OBJECTIVES: Over last 13 years various studies have been done to evaluate the circadian pattern in cardiovascular and cerebrovascular diseases in adults and the existence of such variation in Indian population also has been demonstrated. The data on this variation in geriatric patients does not exist. METHODS: We undertook this prospective observational study at Government Medical College and Hospital, Chandigarh to evaluate the circadian variation in disorders like acute myocardial infarction (AMI), unstable angina (USA), non Q wave MI (non QMI), cerebrovascular accidents (strokes, both ischemic and hemorrhagic) and transient ischemic attacks (TIA). OBSERVATIONS: We studied 158 patients (56.98% males and 43.02% females), mean age was 69 +/- 4 years. 34.17% each had AMI and CVA, 22.78% and USA and 7.59% had NON Q MI, only two patients in our study group had TIAs. We divided 24 hours into four equal quarters each for analysis. RESULTS: We observed that maximum episodes were seen during the period between 6 am till 12 noon 58/158 (36.71%) and a second peak was seen during 6 pm and 12 midnight when 40/158 events were recorded (25.31%). The least number of episodes were seen during the period between 12 midnight till 6 am 22/158 (13.92%). Similar peaking of events was noted for acute myocardial infarction but only one peak was seen for unstable angina. For cerebrovascular accidents two similar peaks were noted between 6 am till 12 noon and 12 noon till 6 pm. CONCLUSIONS: Our study population (geriatric patients) shows the presence of a definitive circadian variation with two comparable peaks. One during the morning hours (6 am-12 noon) and another peak between 6 pm and 12 midnight in patients having acute coronary diseases. In cerebrovascular accidents patients too, similar peaks were noted between 6 am till 12 noon and 12 noon till 6 pm.

Age Distribution↗
PubMed2001

Interconversion of free sugars in relation to activities of enzymes catalyzing synthesis and cleavage of sucrose in growing stem tissues of sorghum.

Free sugar interconversion and activities of soluble acidic (pH 4.8) and neutral (pH 7.5) invertases, sucrose synthase (synthesis) and sucrose phosphate synthase were investigated in the growing nodes and internodes of sorghum (Sorghum vulgare). The results were substantiated with incorporation of 14C from supplied sucrose and hexoses into endogenous sugars of these stem tissues. With the advancement in plant growth, the content of total free sugars in apical nodes and internodes increased till 70 DAS (flowering stage) followed by a decline. In the corresponding basal tissues, the sugar build-up continued even beyond this stage of plant growth. Compared with basal stem tissues, the apical ones contained high activities of soluble invertases and a low proportion amongst free sugars of sucrose. The activities of sucrose-hydrolyzing enzymes were higher as compared with those of sucrose-synthesizing ones in both nodes and internodes and with the growth of plant, the activity of neutral invertase increased in these tissues. More 14C from supplied sucrose and hexoses appeared in extracted sugars from cut discs of apical nodes and internodes in comparison with their basal counterparts. 14C from supplied sucrose appeared in glucose, fructose and from supplied hexoses appeared in sucrose. The results suggest that in apical nodes and internodes, where a rapid cell division and cell expansion occur, sucrose is obligatorily inverted to meet the increased requirement of hexoses and there is a compartmentalized synthesis and cleavage of sucrose in the nodes and internodes of growing sorghum plant.

Carbohydrate Metabolism↗
PubMed2001

Role of percutaneous bone marrow grafting in delayed unions, non-unions and poor regenerates.

The present study comprises of 72 patients of post traumatic delayed unions, established non-unions, poor regenerate in segmental bone transportation and limb lengthening procedure treated by percutaneous injections of autogenous bone marrow at the site of failed healing. The average follow up was 4 years. Bone union was achieved in 68 patients. Overall, 72.2% of the patients had an excellent result, 11.1% a good result, 11.1% a fair result and 5.5% a poor result or failure. These results with only 4 failures (5.5%) are encouraging and suggest that percutaneous autogenous bone marrow grafting is a simple, safe and useful technique in the treatment of delayed unions and non-unions. We believe that this technique of percutaneous autogenous bone marrow grafting can be a procedure of choice in those patients where Phemister or Forbes methods of bone grafting alone is required, especially in limbs with scarred and poor soft tissue coverage. This procedure can also be useful in iatrogenic delayed or non-unions which is the commonest cause of non-union in present era of enthusiastic fracture fixation.

Bone Marrow Transplantation↗
PubMed2001

Gastrointestinal stromal tumors the assessment of malignant potential.

GISTS are the largest category of non-epithelial neoplasms of stomach and small bowel. Numerous immunohistochemical, ultrastructural and flow cytometry studies have been carried out for evaluation of prognostic factors which could predict malignant behaviour of these neoplasms. Tumor size of 5 cm and mitosis of 2/10 hpf were suggested as two important parameters which could predict the chances of recurrence and clinically aggressive course. The aim of this study is to examine predictive value of these two important parameters in assigning the tumors as high, intermediate and low risk groups. Using these two parameters we categorized 30 cases of GIST over a period of 6 years (1990-95) into low, intermediate and high risk groups and examined other features of these cases. Based on these two parameters alone we found that 4 cases each in low and intermediate group could be assigned to a higher risk group clinically as there were presence of adjacent organ infiltration, lymphatic emboli, serosal nodules, lymph node metastasis and transmural infiltration. Hence, other features like hemorrhage, necrosis and anaplasia should also be included in risk assessment. Metaplastic tissues like bone, cartilage and adipose tissues were seen only in high-risk categories.

Adolescent↗
PubMed2000

Antioxidant enzyme expression and reactive oxygen species damage in prostatic intraepithelial neoplasia and cancer.

BACKGROUND: Oxidative stress results in damage to cellular structures and has been linked to many diseases, including cancer. The authors sought to determine whether the expression of three major antioxidant enzymes, copper-zinc superoxide dismutase (SOD1), manganese superoxide dismutase (SOD2), and catalase, was altered in human prostate carcinoma and its likely precursor, high grade prostatic intraepithelial neoplasia (PIN). The level of reactive oxygen species damage was evaluated by measuring the expression of the DNA adduct 8-hydroxydeoxyguanosine. METHODS: The authors evaluated the tissue expression of the antioxidant enzymes in prostate carcinoma by immunohistochemistry, immunogold electron microscopy, and enzymatic assay. The polymerase chain reaction was used to amplify and screen tissue specimens for the genes of SOD1, SOD2, and extracellular SOD (SOD3). Matched paraffin embedded tissue sections were evaluated by RNA in situ hybridization for expression of SOD1 and immunohistochemically for the DNA adduct 8-hydroxydeoxyguanosine. RESULTS: All prostatic tissues, including cancer, displayed immunoreactivity for the three antioxidant enzymes in epithelial cells, with no staining of the stroma, inflammatory cells, or endothelial cells. The number of immunoreactive cells was greater in benign epithelium than in PIN and cancer for each enzyme. The mean percentage and intensity of immunoreactive cells was greatest for SOD2, intermediate for SOD1, and lower for catalase. Staining in cancer was heterogeneous. Immunogold ultrasound studies revealed strong mitochondrial labeling for SOD2, which was greater in benign epithelium than in cancer; SOD1 labeling was invariably weaker, with nuclear labeling in benign epithelium and cytoplasmic labeling in cancer cells. There was no difference in enzyme activity for the three antioxidant enzymes between benign epithelium and cancer. No mutations were found in the 5 exons of SOD1, 5 exons of SOD2, and 3 exons of SOD3, except for 3 of 20 cases with polymorphisms for exon 3 of SOD1. Intense nuclear immunoreactivity for 8-hydroxydeoxyguanosine was present in fewer than 3% of epithelial cells, with no apparent differences among benign epithelium, PIN, and cancer. CONCLUSIONS: SOD1, SOD2, and catalase had lower expression in PIN and prostate carcinoma than in benign epithelium. The number of immunoreactive cells in PIN was similar to cancer, indicating that these are closely related. Enzyme activities were variable, with no difference between benign epithelial cells and cancer, although this lack of change in enzyme activity could have been due to the presence of contaminating benign cells within the cancer specimens. The results of reactive oxygen species damage were found only in the epithelium and not in the stroma. Expression of the DNA adduct 8-hydroxydeoxyguanosine was present in fewer than 3% of cells, with no apparent differences among benign epithelium, PIN, and cancer. These findings suggest that oxidative stress is an early event in carcinogenesis.

Aged↗
PubMed2000

Arginase activity in human breast cancer cell lines: N(omega)-hydroxy-L-arginine selectively inhibits cell proliferation and induces apoptosis in MDA-MB-468 cells.

L-Arginine is the common substrate for two enzymes, arginase and nitric oxide synthase (NOS). Arginase converts L-arginine to L-ornithine, which is the precursor of polyamines, which are essential components of cell proliferation. NOS converts L-arginine to produce NO, which inhibits proliferation of many cell lines. Various human breast cancer cell lines were initially screened for the presence of arginase and NOS. Two cell lines, BT-474 and MDA-MB-468, were found to have relatively high arginase activity and very low NOS activity. Another cell line, ZR-75-30, had the highest NOS activity and comparatively low arginase activity. The basal proliferation rates of MDA-MB-468 and BT-474 were found to be higher than the ZR-75-30 cell line. N-Hydroxy-L-arginine (NOHA), a stable intermediate product formed during conversion of L-arginine to NO, inhibited proliferation of the high arginase-expressing MDA-MB-468 cells and induced apoptosis after 48 h. NOHA arrested these cells in the S phase, increased the expression of p21, and reduced spermine content. These effects of NOHA were not observed in the ZR-75-30 cell line, which expresses high NOS and relatively low arginase. The effects of NOHA were antagonized in the presence of L-ornithine (500 microM), which suggests that in MDA-MB-468 cell line, the arginase pathway is very important for cell proliferation. Inhibition of the arginase pathway led to depletion of intracellular spermine and apoptosis as observed by terminal deoxynucleotidyl transferase (Tdt)-mediated nick end labeling assay and induction of caspase 3. In contrast, the ZR-75-30 cell line maintained its viability and its L-ornithine and spermine levels in the presence of NOHA. We conclude that NOHA has antiproliferative and apoptotic actions on arginase-expressing human breast cancer cells that are independent of NO.

Apoptosis↗
PubMed2000

Castration increases and androgens decrease nitric oxide synthase activity in the brain: physiologic implications.

Sex differences in nitric oxide synthase (NOS) activity in different regions of the rat brain and effects of testosterone and dihydrotestosterone (DHT) treatment in orchidectomized animals were investigated. Regional but no sex differences in NOS activity were detected in gonadectomized animals. Orchidectomy significantly increased NOS activity in the hypothalamus, "amygdala," and cerebellum but not in the cortex. In the hypothalamus, the increase in NOS activity after castration and its reversal by androgen treatment was mimicked by changes in neuronal NOS mRNA level. In contrast, androgen receptor (AR) mRNA level in the hypothalamus was slightly reduced by castration and increased by treatment with DHT. Again in the hypothalamus, the increase in NOS activity in castrated rats was accompanied by an increase in the number of neuronal NOS+ cells determined immunohistochemically, whereas androgen treatment prevented this increase. The changes in NOS+ neurons correlated with the changes in the number of AR+ cells to a degree. Overlap of AR in NOS+ cells was not present in the regions of the hypothalamus analyzed. These results indicate that testosterone or, most likely, its metabolite DHT down-regulates NOS activity, mRNA expression or stabilization, and the number of neuronal NOS+ neurons.

Animals↗
PubMed2000

Exploration of antifilarial potential and possible mechanism of action of the root extracts of Saxifraga stracheyion on cattle filarial parasite Setaria cervi.

The effect of aqueous and alcohol extracts of the roots of Saxifraga stracheyi Engl. On the spontaneous movements of both the whole worm and the nerve muscle preparation of Setaria cervi and on the survival of microfilariae in vitro was studied. Both extracts caused the inhibition of spontaneous movements of the whole worm and the nerve-muscle preparation of S. cervi, characterized by an increase in the amplitude and a decrease in the rate of contractions, while the tone of the contractions remained visibly unaffected. The concentration required to inhibit the movements of the whole worm preparation was 140 microg/ml for the aqueous and 250 microg/ml for the alcohol extract. The concentration of S. stracheyi extracts required to produce an equivalent effect on the nerve-muscle preparation was 30 microg/ml for aqueous, and 20 microg/ml for the alcohol extract, suggesting a cuticular permeability barrier.

Animals↗
PubMed2000

Free cholesterol enhances adenoviral vector gene transfer and expression in CAR-deficient cells.

Efficient adenovirus vector-mediated gene transfer depends on the presence of sufficient amounts of the high-affinity coxsackie-adenovirus (Ad) receptor (CAR) on the surface of the target cell leading to receptor-mediated endocytosis of the vector. The present study evaluates the effect of free cholesterol, a lipid component of endocytic vesicles, on Ad uptake into CAR-deficient cells. Infection in the presence of free cholesterol at its maximum solubility in water led to increased binding, uptake, and expression of Ad in human skin fibroblasts and alveolar macrophages, two primary human cells known to be deficient in CAR. The effect of free cholesterol was maximal at its solubility maximum in aqueous solution. Increase of Ad vector-mediated gene transfer with cholesterol was dependent on the lack of CAR receptor expression on the surface and was diminished by overexpression of CAR in CAR-deficient cells. Cholesterol-mediated increase of Ad-mediated gene expression was dependent on coincubation of both cholesterol and Ad and was not dependent on the cholesterol content of the cell. Increased Ad vector-mediated gene expression in the presence of free cholesterol was also observed in murine skin in vivo. Structural analysis of the Ad-cholesterol mixture showed complexation between Ad particles leading to formation of multivirus aggregates due to hydrophobic interaction. The addition of free cholesterol with Ad vectors may be a simple way to increase Ad-mediated gene transfer to cells that are poor targets due to their lack of a sufficient number of Ad receptors.

Adenoviridae↗
PubMed2000

A comparative survival evaluation and assessment of interclassification concordance in adult supratentorial astrocytic tumors.

Classification and grading of astrocytic tumors has been the subject of several controversies and no universally accepted classification system is yet available. Nevertheless, acceptance of a common system is important for assessing prognosis as well as easy comparative evaluation and interpretation of the results of multi-center therapeutic trials. We report the results of a single center study on comparative survival evaluation along with assessment of inter-classification concordance in 102 cases of supratentorial astrocytic tumors in adults ((3) (3)16 years of age). Hematoxylin and eosin (H&E) stained slides of these 102 cases were reviewed independently by two pathologists and each case classified or graded according to four different classification systems viz. Kernohan, Daumas-Duport (SAM-A), TESTAST-268 and WHO. The histological grading was then correlated with the survival curves as estimated by the Kaplan-Meier method. The most important observation was that similar survival curves were obtained for any one grade of tumor by all the four classification systems. Fifty three of the 102 cases (51.9%) showed absolute grading concordance using all 4 classifications with maximum concordant cases belonging to grades 2 and 4. Intra-classification grade-wise survival analysis revealed a statistically significant difference between grade 2 and grades 3 or 4, but no difference between grades 3 and 4 in any of the classification systems. It is apparent from the results of this study that if specified criteria related to any of the classification systems is rigorously adhered to, it will produce comparable results. Hence, preferential adoption of any one classification system in practice will be guided by the relative ease of histologic feature value evaluation with maximum possible objectivity and reproducibility. We recommend the Daumas-Duport (SAM-A) system since it appears to be the simplest, most objectivized for practical application and highly reproducible with relative ease.

Adolescent↗
PubMed2000

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Adolescent↗
PubMed2000

Circadian periodicity of urinary volume, creatinine and 5-hydroxyindole acetic acid excretion in healthy Indians.

The circadian periodicity of urinary output, creatinine (Cr) and 5-hydroxyindole acetic acid (5-HIAA) excretion was studied under near-tropical conditions in 130 healthy volunteers (65 men and 65 women, 16-75 years of age) with a diurnal activity from about 06:30 to about 22:00 and nocturnal rest. These volunteers were divided into 4 groups, 16-30, 31-45, 46-60 and 61-75 years of age, comprising 20, 20, 15 and 10 participants of each gender, respectively. A marked circadian rhythm was recorded for urine volume, Cr and 5-HIAA excretion in healthy Indians of different ages. The acrophase tended to be delayed in the older age group. The relative amplitude decreased with advancing age, notably in women. Overall, men produced a larger urine volume as compared to women. Excretions of Cr and 5-HIAA in healthy Indian volunteers of different ages may be influenced by diet, societal relations, climate and/or geographic location. The contribution of such factors in metabolism and degradation warrants further study.

Adolescent↗
PubMed2000

Mechanisms of immune dysfunction in stem cell transplantation.

High dose therapy (HDT) and stem cell transplantation (SCT) results in alterations in the immunologic network, thymic re-education and the induction of peripheral tolerance. The changes to the immunoregulatory cascade and tolerance induction associated with autotransplants have been investigated in a series of studies focused on leukocyte reconstitution and function following HDT and autologous SCT. In these studies, we observed a significant decrease in the CD4:CD8 T cell ratio post-transplantation compared to normal peripheral blood (PB) donors due to a decrease in CD4+ cells. In addition, T cell function (phytohemagglutinin (PHA) mitogenesis) was consistently depressed compared to samples obtained from normal PB donors. The loss of T cell function was associated with an increased frequency of circulating monocytes, their expression of Fas ligand (FasL) and a high frequency of apoptotic CD4+ T cells. Indeed, 28-51% of circulating CD4+ T cells were observed to be apoptotic during the first 100 days following HDT and SCT. These studies suggest that 'primed' or activated Fas+ CD4+ lymphocytes interact with FasL+ monocytes, resulting in apoptosis, leading to the preferential deletion of CD4+ T cells, a decrease in the CD4:CD8 T cell ratio and depressed T cell function. Further, as discussed herein, the T cells are activated with a predominantly type 2 phenotype, which may also contribute to the maintenance of the immunosuppressive condition. Therefore, there is the potential to regulate immune recovery by stem cell product manipulation or post-transplantation cytokine administration.

Antineoplastic Agents↗
PubMed2000

A new secoiridoid glycoside from Lonicera angustifolia.

A new secoiridoid glycoside, 6'-O-beta-apiofuranosylsweroside (1), together with the known compounds sweroside, loganin, beta-sitosterol, oleanolic acid, ursolic acid and methyl-4-hydroxy benzoate have been identified from the leaves of Lonicera angustifolia. The structure of the new compound has been elucidated on the basis of spectroscopic and chemical evidence.

Glucosides↗