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Biomedical subjects

V Singh

Publications and source records attributed to V Singh.

At least 55 records · Page 3Linked to original sources

Barriers in the management of asthma and attitudes towards complementary medicine.

BACKGROUND: Undertreatment is said to be an important problem for those with asthma. Misconceptions regarding the nature and treatment of asthma may contribute to this. This study was planned to evaluate the perception of those with asthma about various aspects of their condition. METHODS: A total of 1012 patients with asthma volunteered to complete the questionnaire. Questions included those regarding severity, nature, regularity of use of medicine and attitudes towards trying complementary medicine. Forced expiratory volume in 1 s (FEV1) was measured to assess the severity of airway obstruction. RESULTS: Only 9% of patients took treatment for asthma according to the advice of the doctor. The remainder reported stopping treatment when they became free of symptoms or were able to tolerate their symptoms. A majority of the patients had moderately severe airway obstruction as determined by spirometer and reported being unable to assess the severity of their disease with only 11.9% reporting that they could perceive the warning symptoms of an acute attack. Seventy-nine percent of the patients had used complementary medicine. Home remedies, such as tea, hot water, walking, ginger and turmeric, were perceived to provide relief in asthma. CONCLUSION: Patients with asthma have many barriers in the way of optimal treatment. These include a failure to recognize warning symptoms, belief in a permanent cure; not continuing treatment for as long as needed; and, an inclination to seek complimentary medicines.

Adolescent↗

Oropharyngeal carriage and lower airway colonisation/infection in 45 tracheotomised children.

BACKGROUND: A study was undertaken to determine the oropharyngeal carrier state of potentially pathogenic microorganisms (PPM) and the magnitude of colonisation and infection rates of the lower airways with these PPM in children requiring long term ventilation first transtracheally and afterwards via a tracheotomy. METHODS: A 5 year, prospective, observational cohort study was undertaken in 45 children (33 boys) of median age 6.4 months (range 0-180) over a 5 year period at the Royal Liverpool Children's NHS Trust of Alder Hey, a university affiliated tertiary referral centre. The children were first admitted to the 20-bed paediatric intensive care unit (PICU) and, following placement of a tracheotomy, they were transferred to a four bedded respiratory ward. The two main indications were neurological disorders and airway obstruction. All children were ventilated transtracheally for a median period of 12 days (range 0-103) and, after placement of the tracheotomy, for a similar period of 12 days (range 1-281). Surveillance cultures of the oropharynx were taken on admission to the PICU and on the day of placement of the tracheotomy. Throat swabs were taken twice weekly during ventilation, both transtracheal and via the tracheotomy. Tracheal aspirates were taken once weekly and when clinically indicated (in cases where the lower airway secretions were turbid). RESULTS: Twenty five patients (55%) had abnormal flora, mainly aerobic Gram negative bacilli (AGNB), particularly Pseudomonas aeruginosa, while the community PPM Staphylococcus aureus was present in the oropharynx of 37% (17/45) of the study population. The lower airways were sterile in six children; the other 39 patients (87%) had a total of 82 episodes of colonisation. "Community" PPM significantly increased once the patients received a tracheotomy, independent of the number of patients enrolled, episodes of colonisation/infection, and the number of colonised/infected patients. "Hospital" PPM significantly decreased after tracheotomy only when episodes were compared. CONCLUSIONS: While P aeruginosa present in the admission flora caused primary endogenous colonisation/infection during mechanical ventilation on the PICU, S aureus not carried in the throat was responsible for the exogenous colonisation/infection once the patients had a tracheotomy. This is in sharp contrast to adult studies where exogenous infections are invariably caused by AGNB. This discrepancy may be explained by chronic underlying conditions such as diabetes, alcoholism, and chronic obstructive pulmonary disease which promote AGNB, whereas the children were recovering following tracheotomy.

Adolescent↗

Truncated equine LH beta and asparagine(56)-deglycosylated equine LH alpha combine to produce a potent FSH antagonist.

Hybrid hormone preparations were prepared by combining intact and Asn(56)-deglycosylated (N(56)dg) equine (e) LH or FSH alpha subunit preparations with truncated, des(121-149)eLH beta (eLH beta t), immunopurified, intact eLH beta or equine chorionic gonadotropin beta (eCG beta) preparations, and eFSH beta. The LH receptor-binding potencies of N(56)dg-eLH alpha:eLH beta t and N(56)dg-eFSH alpha:eLH beta t hybrids were equivalent to that of eLH; however, both N(56)dg-alpha preparations were only 3-4% as active as eLH in the rat testis Leydig cell bioassay. In the granulosa cell FSH bioassay, eLH alpha:eLH beta t stimulated progesterone synthesis and induced aromatase activity, while N(56)dg-eLH alpha:eLH beta t was completely inactive at doses up to 5 microg. N(56)dg-eLH alpha:eLH beta t inhibited progesterone production and aromatase induction elicited by 0.3 ng eFSH or 2 ng human (h) FSH. The inhibitory activities of N(56)dg-eLH alpha:eLH beta and N(56)dg-eCG alpha:eLH beta t were only 10% that of N(56)dg-eLH alpha:eLH beta t. N(56)dg-eLH alpha:eCG beta did not inhibit progesterone synthesis stimulated by eFSH at all and appeared to further stimulate aromatase induction at the highest dose tested. Preincubation of N(56)dg-eLH alpha:eLH beta and N(56)dg-eLH alpha:eLH beta t for 72 h at 37 C resulted in no loss of FSH receptor-binding activity. Preincubation resulted in 50% loss of receptor-binding activity by the eFSH preparation due to subunit dissociation, while 88% of N(56)dg-eLH alpha:eFSH beta activity was lost following 72 h, 37 C preincubation. While alpha Asn(56) oligosaccharide had no effect on eLH beta hybrid stability, it did contribute to the stability of the eFSH heterodimer.

Animals↗

Evaluation of communication skills of physicians about asthma.

OBJECTIVE: Communication skills in medical practice are important. To assess the communication skills of physicians about asthma, we undertook this study. METHODS: One thousand four hundred and twenty one physicians attending the annual conference of association of physicians of India volunteered to participate in the study. They were divided into three categories. 'Teachers' group 1, (n = 131), 'Clinicians', group 2, (n = 951) and 'Students' group 3, (n = 339). Questionnaire containing ten most frequently asked questions by asthmatic patients were given to the physicians. A panel of three patients assessed the replies of these question and graded them as 'Convincing', 'Just convincing' and 'Not convincing'. RESULTS: Replies of only 2% of physicians were graded as convincing, 15.6% just convincing and 82.4 as not convincing. Among group 1 none gave a convincing reply while replies of 2.2% of group 2 and 2.4% of group 3 were graded as convincing. The difference in results was not significant statistically on comparing the three groups (p > 0.1). CONCLUSIONS: Communication skills are the integral part of patient care and management. Our study demonstrated lack of effective communication skills among physicians.

Asthma↗

Chronic dyspnea and hyperventilation in an awake patient with small subcortical infarcts.

A 79-year-old woman presented with chronic dyspnea and hyperventilation. There was no evidence of pulmonary disease. Hyperventilation persisted during sleep and after high-dose administration of a narcotic. A head MRI revealed bilateral medial thalamic infarctions. Central neurogenic hyperventilation was diagnosed in this alert patient. The case may illustrate a role for the thalamus in regulating ventilation, but another small infarct not visible on MRI also could be responsible.

Aged↗

Pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase/MAPK cascade interact synergistically with UCN-01 to induce mitochondrial dysfunction and apoptosis in human leukemia cells.

Interactions between the checkpoint abrogator UCN-01 and several pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) kinase (MEK)/MAPK pathway have been examined in a variety of human leukemia cell lines. Exposure of U937 monocytic leukemia cells to a marginally toxic concentration of UCN-01 (e.g., 150 nM) for 18 h resulted in phosphorylation/activation of p42/44 MAPK. Coadministration of the MEK inhibitor PD184352 (10 microM) blocked UCN-01-induced MAPK activation and was accompanied by marked mitochondrial damage (e.g., cytochrome c release and loss of DeltaPsi(m)), caspase activation, DNA fragmentation, and apoptosis. Similar interactions were noted in the case of other MEK inhibitors (e.g., PD98059; U0126) as well as in multiple other leukemia cell types (e.g., HL-60, Jurkat, CCRF-CEM, and Raji). Coadministration of PD184352 and UCN-01 resulted in reduced binding of the cdc25C phosphatase to 14-3-3 proteins, enhanced dephosphorylation/activation of p34(cdc2), and diminished phosphorylation of cyclic AMP-responsive element binding protein. The ability of UCN-01, when combined with PD184352, to antagonize cdc25C/14-3-3 protein binding, promote dephosphorylation of p34(cdc2), and potentiate apoptosis was mimicked by the ataxia telangectasia mutation inhibitor caffeine. In contrast, cotreatment of cells with UCN-01 and PD184352 did not substantially increase c-Jun-NH(2)-terminal kinase activation nor did it alter expression of Bcl-2, Bcl-x(L), Bax, or X-inhibitor of apoptosis. However, coexposure of U937 cells to UCN-01 and PD184352 induced a marked increase in p38 MAPK activation. Moreover, SB203580, which inhibits multiple kinases including p38 MAPK, partially antagonized cell death. Lastly, although UCN-01 +/- PD184352 did not induce p21(CIP1), stable expression of a p21(CIP1) antisense construct significantly increased susceptibility to this drug combination. Together, these findings indicate that exposure of leukemic cells to UCN-01 leads to activation of the MAPK cascade and that interruption of this process by MEK inhibition triggers perturbations in several signaling and cell cycle regulatory pathways that culminate in mitochondrial injury, caspase activation, and apoptosis. They also raise the possibility that disrupting multiple signaling pathways, e.g., by combining UCN-01 with MEK inhibitors, may represent a novel antileukemic strategy.

Alkaloids↗

An essential role of the NF-kappa B/Toll-like receptor pathway in induction of inflammatory and tissue-repair gene expression by necrotic cells.

Tissue damage induced by infection or injury can result in necrosis, a mode of cell death characterized by induction of an inflammatory response. In contrast, cells dying by apoptosis do not induce inflammation. However, the reasons for underlying differences between these two modes of cell death in inducing inflammation are not known. Here we show that necrotic cells, but not apoptotic cells, activate NF-kappaB and induce expression of genes involved in inflammatory and tissue-repair responses, including neutrophil-specific chemokine genes KC and macrophage-inflammatory protein-2, in viable fibroblasts and macrophages. Intriguingly, NF-kappaB activation by necrotic cells was dependent on Toll-like receptor 2, a signaling pathway that induces inflammation in response to microbial agents. These results have identified a novel mechanism by which cell necrosis, but not apoptosis, can induce expression of genes involved in inflammation and tissue-repair responses. Furthermore, these results also demonstrate that the NF-kappaB/Toll-like receptor 2 pathway can be activated both by exogenous microbial agents and endogenous inflammatory stimuli.

Animals↗

NF-kappa B RelA (p65) is essential for TNF-alpha-induced fas expression but dispensable for both TCR-induced expression and activation-induced cell death.

The Fas death receptor plays a key role in the killing of target cells by NK cells and CTLs and in activation-induced cell death of mature T lymphocytes. These cytotoxic pathways are dependent on induction of Fas expression by cytokines such as TNF-alpha and IFN-gamma or by signals generated after TCR engagement. Although much of our knowledge of the Fas death pathway has been generated from murine studies, little is known about regulatory mechanisms important for murine Fas expression. To this end, we have molecularly cloned a region of the murine Fas promoter that is responsible for mediating TNF-alpha and PMA/PHA-induced expression. We demonstrate here that induction of Fas expression by both stimuli is critically dependent on two sites that associate with RelA-containing NF-kappaB complexes. To determine whether RelA and/or other NF-kappaB subunits are also important for regulating Fas expression in primary T cells, we used CD4 T cells from RelA(-/-), c-Rel(-/-), and p50(-/-) mice. Although proliferative responses were significantly impaired, expression of Fas and activation-induced cell death was unaffected in T cells obtained from these different mice. Importantly, we show that unlike fibroblasts, which consist primarily of RelA-containing NF-kappaB complexes, T cells have high levels of both RelA and c-Rel complexes, suggesting that Fas expression in T cells may be dependent on redundant functions of these NF-kappaB subunits.

3T3 Cells↗

Lipid profile in the progeny of parents with ischemic heart disease.

Lipid profile of 50 offsprings of parents with ischemic heart disease and 15 control children aged 5-16 years was studied. The children in both the groups were categorized into 3 sub groups, 5-10, 11-15 & > 15 years. The Serum total cholesterol levels (mean +/- S.D) (in mg/dl) in the test group were 169.8 +/- 15.13, 173.34 +/- 33.56, 177.4 +/- 27.89 respectively for the 3 age subgroups. The Serum LDL cholesterol levels (mean +/- S.D) (in mg/dl) in the test group were 102.2 +/- 15.25, 95.13 +/- 30.38, 101.09 +/- 26.96 respectively. The serum total cholesterol levels (mean +/- S.D) (in mg/dl) in the control group were 123 +/- 1.33, 118 +/- 7.51 and 127.4 +/- 5.77 respectively for the 3 age subgroups. The serum LDL cholesterol levels (mean + S.D) (in mg/dl) in the control group were 56.64 +/- 8.75, 43.36 +/- 6.10 and 45.16 +/- 6.78 respectively. The serum total cholesterol and LDL cholesterol levels in the test group were significantly higher as compared to controls (p > 0.05). Among test subjects, 54% had elevated total cholesterol (> 170 mg/dl) and 38% had elevated LDL cholesterol (> 110 mg/dl). These cases had a significant correlation with elevated parental total cholesterol and LDL cholesterol levels (p > 0.05). Thus, a selective screening of the offsprings of parents with premature ischemic heart disease and hypercholesterolemia is advocated.

Adolescent↗

The role of endoscopic procedures in the management of postcholecystectomy and posttraumatic biliary leak.

Endoscopic retrograde cholangiopancreatography (ERCP) is an important tool in the evaluation of the biliary system. It not only diagnoses the site of biliary leak following bile duct injury, but it also acts as a therapeutic modality to allow interventional procedures such as sphincterotomy, nasobiliary drainage, or stent placement to be performed. The present study was carried out to evaluate the role of endoscopic management of biliary leak, following either liver trauma or cholecystectomy. Of a total 21 patients with bile leak following liver trauma and biliary surgery, 20 were managed by various endoscopic procedures. In the postcholecystectomy group, ERCP revealed a cystic duct leak in 9 patients and common bile duct injury in 6 patients. These complications were managed by sphincterotomy alone in 2 patients, by nasobiliary drainage alone in 4 patients, by sphincterotomy and nasobiliary drainage in 8 patients, and by sphincterotomy and stent placement in 1 patient. Posttraumatic biliary fistula was successfully managed by performing sphincterotomy followed by the placement of nasobiliary drainage in all of five patients who had suffered trauma injury.

Adult↗

Diferuloylputrescine and p-coumaroyl-feruloylputrescine, abundant polyamine conjugates in lipid extracts of maize kernels.

Extraction of corn bran or corn fiber with polar solvents such as methylene chloride, ethanol or chloroform/methanol yielded common lipids and two unknown high-performance liquid chromatography (HPLC) peaks, each with an ultraviolet absorbance maximum at 320 nm. HPLC-mass spectrometry revealed that the unknowns were diferuloylputrescine (DFP) and p-coumaroyl-feruloylputrescine (CFP). When compared to extracts of corn fiber (a pericarp-enriched fraction from the wet milling of corn), comparable extracts of corn bran (a pericarp- enriched fraction from the dry milling of corn) yielded three- to eightfold higher levels of DFP and CFP. Extraction of corn bran or fiber with an accelerated solvent extractor revealed that elevated temperatures greatly enhanced the extraction of DFP and CFP by methylene chloride and ethanol. "Corn bran oil," prepared by extraction of corn bran with hot methylene chloride, contained 14 wt% DFP and 3 wt% CFP. However, when hexane was used as a solvent, accelerated solvent extraction of the corn bran or fiber did not extract any DFP or CFP. Extraction of wheat bran or psyllium hulls with hot methylene chloride did not yield any detectable DFP or CFP. Because it has been suggested that polyamine conjugates such as DFP and CFP may function as natural pesticides, a rapid method was developed to purify them so that their biological activity could be evaluated.

Biochemistry↗

Analysis and properties of arabinoxylans from discrete corn wet-milling fiber fractions.

Three fibrous corn wet-milling fractions, coarse fiber, fine fiber, and spent flake, were isolated. More highly valued uses are sought for these milling products, which are generally directed into the corn gluten feed product stream. Coarse fiber was further dissected into pericarp and aleurone layers. An alkaline hydrogen peroxide process was used to efficiently extract corn fiber gum (CFG) from each of the materials. CFG is a hemicellulose B arabinoxylan which also contains low levels of D,L-galactose and D-glucuronic acid. CFG yield information was obtained from each source, as well as structural information in terms of degrees of branching of the beta-D-xylopyranose backbone with alpha-L-arabinofuranosyl moieties. There were significant differences in degree of branching among the CFGs from the various fractions. A novel capillary electrophoresis procedure was developed to measure these differences. Solution viscosity differences among the CFGs were also observed.

Dietary Fiber↗

Comparison of oil and phytosterol levels in germplasm accessions of corn, teosinte, and Job's tears.

Seeds of 49 accessions of corn (Zea mays ssp. mays), 9 accessions of teosinte (Zea species that are thought to be ancestors and probable progenitors to corn), and 3 accessions of Job's tears (Coix lacryma), obtained from a germplasm repository, were ground and extracted with hexane. Whole kernel oil yields and levels of four phytonutrients (free phytosterols, fatty acyl phytosterol esters, ferulate phytosterol esters, and gamma-tocopherol) in the oils were measured. Among the seeds tested, oil yields ranged from 2.19 to 4.83 wt %, the levels of ferulate phytosterol esters in the oil ranged from 0.047 to 0.839 wt %, the levels of free phytosterols in the oil ranged from 0.54 to 1.28 wt %, the levels of phytosterol fatty acyl esters in the oil ranged from 0.76 to 3.09 wt %, the levels of total phytosterols in the oil ranged from 1.40 to 4.38 wt %, and the levels of gamma-tocopherol in the oil ranged from 0.023 to 0.127 wt %. In general, higher levels of all three phytosterol classes were observed in seed oils from accessions of Zea mays ssp. mays than in seed oils from accessions of the other taxonomic groups. The highest levels of gamma-tocopherol were observed in teosinte accessions.

Corn Oil↗

Melatonin enhances Th2 cell mediated immune responses: lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists.

Chronic administration of melatonin for 5 days to antigen-primed mice increased the production of pro-inflammatory cytokine IL-10 but decreased the secretion of anti-inflammatory cytokine TNF-alpha. These results further confirm that melatonin activates Th2-like immune response. Whether melatonin-mediated Th2 response is dependent on opioid or central and peripheral benzodiazepine receptors was also examined. Hence, melatonin was administered to antigen-sensitised mice with either naltrexone (a mu opioid receptor antagonist) or flumazenil (a central benzodiazepine receptor antagonist) or PK11195 (a peripheral benzoidiazepine receptor antagonist). No significant difference in melatonin-induced Th2 cell response was observed by naltrexone, flumazenil or PK11195 treatment. These findings suggest that the Th2 cell response induced by melatonin in antigen sensitised mice neither dependent on endogenous opioid system nor is modulated through the central or peripheral benzodiazepine receptors.

Animals↗

Melatonin provides signal 3 to unprimed CD4(+) T cells but failed to stimulate LPS primed B cells.

Growing evidence has supported the conclusion that melatonin, a pineal hormone, modulates the immune function. In our previous study, we evaluated in vivo the potential role of melatonin in the regulation of the antigen specific T and B cells. In the present study, we observe that melatonin down-regulated the expression of the co-stimulatory molecule B7-1 but not B7-2 on macrophages. Further, melatonin encouraged the proliferation of anti-CD3 antibody activated CD4(+) T cells only in the presence of antigen-presenting cells and promoted the production of Th2-like cytokines. Furthermore, it failed to influence the activity of B cells in a T-independent manner. Melatonin suppressed the release of TNF-alpha by LPS or IFN-gamma activated macrophages but failed to inhibit nitric oxide (NO) release. Thus the study shows that melatonin can engineer the growth of unprimed CD4(+) T cells if both the signals are provided by antigen-presenting cells. However, it could not regulate the function of B cells.

Animals↗

Epidemiology of gallstone disease in Chandigarh: a community-based study.

BACKGROUND: Cholelithiasis is frequent in our country (India), and is a common cause for abdominal surgery. We studied the prevalence of gallstone disease and its association with various risk factors in the city of Chandigarh. METHODS: A house-to-house survey of residents aged 15 years or above in a subsector of Chandigarh was conducted as a part of a pilot survey. All individuals with a history of gallstone disease, and equal or more number of asymptomatic individuals were asked to attend the outpatient department of the Postgraduate Medical Institute. On the basis of the pilot survey, the sample size to be studied was 2648 and we screened 2649 persons. RESULTS: Two hundred and fifty-four individuals attended the outpatient services of the Institute, and 248 underwent an ultrasound. There were 37 symptomatic and 211 asymptomatic individuals (male: female, 93:155). Gallstone disease was seen in 24 out of 37 (64.9%) in the symptomatic, and seven out of 211 (3.3%) in the asymptomatic group. Out of these, 27 females and four males had gallstone disease (mean age: 48.30 +/- 16.03 years). Approximately 67% of patients were between 20 and 60 years of age. Gallstone disease was more frequently seen in those from high socioeconomic status as compared to middle socioeconomic status (chi2 = 8.9, d.f. = 1, P < 0.01), and in multiparous as compared to nulliparous females (chi2 = 4.8, d.f. = 1, P < 0.05). Body mass index, smoking, alcohol consumption, and a vegetarian/non-vegetarian diet did not influence the prevalence of gallstone disease. CONCLUSIONS: Gallstone disease is frequent in northern India. Gallstones were frequent in those belonging to high socioeconomic status and multiparous females. However, body mass index, smoking, alcohol or other dietary habits did not make a difference.

Adolescent↗