PubMed Health⌕ Search

Biomedical subjects

J K Singh

Publications and source records attributed to J K Singh.

At least 19 recordsLinked to original sources
PubMed2005

Effect of tractor driving on hearing loss in farmers in India.

BACKGROUND: Indian tractor drivers operate their tractors and other implements/equipment in an environment which can have extreme temperatures and high level of suspended particulate matter. In addition, Indian tractors do not have adequate vibration and noise attenuating designs features. This cross-sectional study compares the hearing status of tractor driving farmers (TDFs) (study group) and non-tractor driving farmers (NTDFs) (control group) matched for age, sex, generic/ethnic group, land holding, education levels, and work routines. METHOD: Two groups of 50 experienced tractor-driving farmers and 50 non-driving farmers were selected from 2 villages, 50 km from Delhi. All participants were interviewed for details of work routine and noise exposures. An audiogram was performed and noise measurements taken on tractors and other machines. RESULTS: Self-reported hearing problems were similar (4 cases each) in both the groups of 50 farmers. However, audiogram analysis showed higher prevalence of abnormalities in TDFs. TDFs (24) had more often high frequency hearing loss when compared to NTDFs (14). The noise levels observed on tractors in different operations were in the range of 90-110 dB (A). CONCLUSIONS: Tractor noise levels exceeded the recommended safe limits of OSHA and NIOSH prescribed standards. TDFs had higher high frequency hearing loss than NTDFs. The mechanism of damage and prevention needs to be studied further.

Adult↗
PubMed2004

The use of dye in ophthalmology.

Dyes are used in current ophthalmological practice, both as diagnostic and therapeutic aids. Commonly used dyes include sodium fluorescein, indocyanine green, rose bengal and methylene blue. The properties of these agents are outlined, along with indications for their use. The article concentrates mainly on intravenous sodium fluorescein and fundus fluorescein angiography, although topical and intracameral use of other dyes is highlighted. Ocular tissue responses are discussed, in particular those of the retinal vasculature and choroidal circulation. The normal blood-retinal barriers and pathology of abnormal angiography findings is presented. Pharmacokinetics and pharmacodynamics of intravenous dye are discussed, along with potential systemic complications.

Administration, Topical↗
PubMed2000

Racial differences in respiratory-related neonatal mortality among very low birth weight infants.

OBJECTIVE: To examine racial differences in the secular trends in respiratory-related neonatal mortality among very low birth weight (VLBW) infants in the United States, temporally associated with surfactant availability. DESIGN: Comparison of time trends in African American and non-Hispanic white (NHW) VLBW infants of cause-specific neonatal mortality and neonatal and infant mortality for 2 consecutive 3-year periods. RESULTS: From 1985 to 1988 there was no racial difference in the rate of decline of each mortality outcome. From 1988 to 1991 rates of decline in neonatal mortality caused by respiratory distress syndrome and by all respiratory causes were significantly greater for NHWs compared with African Americans. However, the rate of decline in nonrespiratory neonatal mortality was similar for African Americans and NHWs. Compared with African American VLBW infants, NHWs had a greater rate of decline in both neonatal (31% vs 20%; P <.01) and infant mortality (32% vs 21%; P <.01) during this period. CONCLUSIONS: Between 1988 and 1991, declines in neonatal mortality risks caused by respiratory distress syndrome and all respiratory causes were greater for NHW infants than for African American VLBW infants. The decline in nonrespiratory mortality risk showed no racial differences. These findings suggest possible racial disparities in timely access or racial differences in the efficacy of respiratory treatments for VLBW infants.

Black People↗
PubMed2000

Microbicidal activity of MDI-P against Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, and Legionella pneumophila.

BACKGROUND: MDI-P (Medical Discoveries, Inc-Pharmaceutical, Layton, Utah) is a clear, colorless liquid generated by electrolysis of preservative-free and endotoxin-free, nonpyrogenic, sterile, injection saline (0.9% NaCl, wt/vol). It contains numerous highly reactive chlorine and oxygen species, including HOCl(-1,) OCl-(1), Cl(-1), Cl(2), O(2-)(1), and O(3). This report presents data on the in vitro microbicidal activity of MDI-P against 4 clinically relevant microbial pathogens that are often difficult to eradicate. METHODS: MDI-P was generated from injection saline by using a patented electrolysis instrument. It was then tested for microbicidal activity at concentrations ranging from 0.01% to 50% against Staphylococcus aureus, Pseudomonas aeruginosa, Legionella pneumophila, and Candida albicans (10(5) to 10(9) colony-forming units/mL). The effect of serum (50% and 90%) and pH on MDI-P activity were also tested. The morphologic effects of MDI-P on microbial cells were studied by light microscopy of cells stained by Gram's method and by transmission electron microscopy. Morbidity, mortality, and the effect of MDI-P on tissues were studied by using a mouse model. RESULTS: The microbicidal activity of MDI-P occurred within the first minute of exposure for all the organisms tested. When 50% MDI-P was tested against cell titers of 10(5) or 10(7) colony-forming units/mL, all test organisms were killed within 1 minute; at lower MDI-P concentrations, C albicans was the most sensitive organism, and L pneumophila was the most resistant. Even with beginning cell titers of 10(9) colony-forming units/mL, killing by 50% MDI-P was >99.9% for all test strains. Furthermore, at the same beginning cell titer, killing of C albicans by MDI-P diluted to 50% with normal human serum rather than injection saline was only slightly reduced. No acute morbidity, mortality, or tissue damage was detected in mice that were intravenously given 17 mL/kg of undiluted MDI-P. CONCLUSIONS: MDI-P is a very fast-acting, broad-spectrum microbicidal material. The lack of evidence for acute morbidity, mortality, or tissue injury, ease of preparation, and low cost suggest that it may be useful for various sterilization and disinfection applications.

Animals↗
PubMed1999

Comparability testing of a humanized monoclonal antibody (Synagis) to support cell line stability, process validation, and scale-up for manufacturing.

Biochemical and functional testing of a humanized monoclonal antibody directed against Respiratory Syncytial Virus (Synagis) has been performed to evaluate cell line stability, support process validation, and to demonstrate "comparability" during the course of process development. Using a variety of analytical methods, product manufactured at different sites and in bioreactors from 20 litres to 10,000 litres was shown to be biochemically and functionally equivalent. The biochemical testing for microheterogeneity found on Synagis included evaluation of changes in post-translational modifications such as deamidation, truncation, and carbohydrate structure. Studies were also performed to support cell line stability assessment and cell culture process validation. Cell culture conditions were deliberately varied in an attempt to determine if this would have an impact on the microheterogeneity of the product. In these studies Synagis was produced from cells cultured beyond the population doublings achieved at the maximum manufacturing scale, under conditions of low glucose, and using harvest times outside of the historical manufacturing operating range. Results showed that there was a different pattern of glycosylation during the early stages of bioreactor culture. No other changes in microheterogeneity were apparent for the other culture conditions studied. In summary, comparability assessment demonstrated that the Synagis manufacturing process is robust and consistent resulting in a predictable and reproducible monoclonal antibody product.

Antibodies, Monoclonal↗
PubMed1999

Trend in mortality from respiratory distress syndrome in the United States, 1970-1995.

OBJECTIVE: We examined the trend in mortality caused by respiratory distress syndrome (RDS) and its impact on changes in infant and neonatal mortality rates (IMR, NMR) in the United States. STUDY DESIGN: Data on infant deaths in the United States for the period 1970 through 1995 were used to compare RDS-specific IMR to other cause-specific IMR. Data from the U.S. birth cohorts of 1985 through 1991 were used to examine birth weight- and RDS-specific NMRs. RESULTS: IMR from RDS declined from 2.6 per 1000 live births in 1970 to 0.4 per 1000 in 1995. More than three quarters of this decline occurred between 1970 and 1985. RDS-specific NMR declined by 13% between 1985 and 1988 and by more than twofold greater, that is, 28%, between 1988 and 1991. There was also a significant reduction in postneonatal mortality from chronic lung diseases between 1988 and 1991. CONCLUSIONS: Most of the reduction in mortality from RDS occurred before the introduction of surfactant therapy. The recent accelerated reduction in mortality from RDS between 1988 and 1991 was temporally associated with widespread use of surfactant therapy and was the single most important factor for reduction in overall NMR in the United States.

Birth Weight↗
PubMed1997

Beneficial effects of fluosol-polyethylene glycol cardioplegia on cold, preserved rabbit heart.

BACKGROUND: Because of its high oxygen-carrying capacity, especially at low temperatures, fluosol may enhance heart preservation. METHODS: Hearts of male New Zealand white rabbits (1.5-2.0 kg) were excised and flushed through the aorta with 0 degree C St. Thomas' Hospital solution, fluosol, or polyethylene glycol or fluosol-polyethylene glycol cardioplegic solution. Hearts were then stored for 12 hours at 0 degree C and reperfused with Krebs-Henseleit buffer at 36.5 degrees C for 60 minutes using a Langendorff system. RESULTS: Myocardial contractile function was significantly greater in the fluosol-polyethylene glycol cardioplegia-preserved group (p < 0.01) and polyethylene glycol-cardioplegia preserved group (p < 0.05) than in the St. Thomas' Hospital solution-preserved group. The myocardial high-energy phosphate content was significantly higher in the fluosol-polyethylene glycol-cardioplegia-preserved group (p < 0.01), with reduced release of lactate dehydrogenase (p < 0.01) in comparison with the St. Thomas' Hospital solution-preserved group. CONCLUSIONS: The addition of fluosol and polyethylene glycol to the cardioplegic solution may enhance long-term cold heart preservation.

Animals↗
PubMed1996

Apoptosis is associated with an increase in saturated fatty acid containing phospholipids in the neuronal cell line, HN2-5.

Two widely different paradigms of stress, hypoxia and nutrient deprivation, were observed to trigger apoptosis in a clonal neuronal (hippocampal) cell line (HN2-5) as judged by DNA laddering analysis and chromatin condensation. Since according to its original definition, apoptosis is concomitant with a dramatic change in cell morphology, the composition of major phospholipids that determine morphological properties of cells was analyzed in this study. We observed a significant increase (10-20%) in the proportion of saturated fatty acid side chains only in phosphatidylethanolamine (PE), phosphatidylserine (PS) and phosphatidylinositol (PI) but not in phosphatidylcholine (PC). This increase was independent of the paradigm of stress used (hypoxia or nutrient deprivation) to initiate apoptosis. Since phospholipids constitute the fabric of both plasma membranes as well as the membranes surrounding the intracellular organelles such as the lysosomes, endoplasmic reticulum and the nuclei, such an apoptosis-associated, selective change in phospholipid composition could cause a dramatic and overall change in membrane fluidity, thus producing the typical shrinking, deformation and porosity of both nuclear as well as plasma and lysosomal membranes as observed in apoptotic cells. Leakiness of lysosomal and nuclear membranes could cause diffusion of deoxyribonucleases into cell nuclei, thus resulting in the characteristic cleavage and laddering of chromosomal DNA which accompany apoptosis.

Antibodies↗
PubMed1996

Cell-specific regulation of the stably expressed serotonin 5-HT1A receptor and altered ganglioside synthesis.

Neurotransmission is dependent on the presence of neuronal receptors at the synapses, and important cell surface molecules such as gangliosides are pivotal in the maintenance of synaptic contacts. To study the interrelationship between these two classes of molecules, we achieved stable expression of the hippocampus- and CNS-localized serotonin 1A receptor (5-HT1A-R) in three 5-HT1A-R-deficient neuronal cell lines and also the control, non-neural CHO cells. A strong passage dependence of 5-HT1A-R expression, as measured by mRNA levels as well as membrane binding to the selective agonist [3H]8-OH-DPAT, was observed only in the HN2 (hippocampal) and NCB-20 (CNS) cells which are derived from tissues of natural occurrence of the 5-HT1A-R. A paradigm of stress was obtained by carrying out continuous culture of cells without feeding. During this time a dramatic increase in 5-HT1A-R mRNA and [3H]8-OH-DPAT binding was observed only in the neuronal cells after confluence and during decreased cell viability (days 10/11). This was not due to differentiation, since deliberate serum deprivation and differentiation of cells did not result in any dramatic increase in 5-HT1A-R expression. Analysis of ganglioside synthesis by pulse labeling of the transfected cells produced striking results. In the dorsal root of the ganglion (DRG) derived F-11 cells which show low but significant levels of complex gangliosides before transfection, the mere presence of the serotonin 1A receptor resulted in a dramatic increase in synthesis of gangliosides comigrating with GM2, GD1a, GD1b, and GT1b (20-fold by densitometry). In contrast, there was only a 2-fold increase in the overall content of complex gangliosides in the presence of the 5-HT1A-R. In the NCB-20 cells which contain only GD1a but no GD1b or GT1b before transfection, a decrease in GD1a synthesis was observed following transfection. Also agonist (8-OH-DPAT) binding to the serotonin 1A receptor in NCB-20 cells produced a 3-fold increase in synthesis of a ganglioside comigrating with GM3. Thus, our neuroblastoma transfectants help demonstrate stress-induced regulation of the 5-HT1A-R, which in turn exerts a strong and cell type-specific control over such essential cell-surface determinants like gangliosides.

Animals↗
PubMed1996

Stable expression and heterologous coupling of the kappa opioid receptor in cell lines of neural and nonneural origin.

Signal transduction cascades initiated by the neuronal kappa opioid receptor were studied following transfection of a neuronal (hippocampal) line, HN2, and the non-neural CHOs. Retinoic-acid mediated differentiation resulted in intense staining of the HN2 cells with a neurofilament protein antibody SMI 33 but not with an antibody to GFAP, thus establishing neuronal characteristics of the HN2 cell line. The kappa opioid receptor was stably expressed in the two cell lines by electroporation mediated transfer of a Cytomegalovirus-promoter driven construct, pCMV-kappa, harboring the kappa-opioid receptor cDNA. Positive clones (HN2 kappa 24 and CHO kappa 18) from both lines showed high expression of the kappa opioid receptor, as identified by [3H] U-69,593 binding to membranes prepared from HN2 kappa 24 and CHO kappa 18. Scatchard analysis revealed the presence of high affinity kappa opioid receptors in both engineered cell lines (KD=1.3 nM for HN2 kappa 24 and 2.1 nM for CHO kappa 18). Functional coupling to adenylate cyclase was displayed by 1 microM U-69,593 mediated inhibition (55-63%) of prostaglandin E1-stimulated intracellular cAMP levels. A major difference between the two clones was observed in functional coupling of the expressed kappa opioid receptor to phospholipases C (PL-C) and D (PL-D). U-69,593 (1 microM) treatment stimulated PL-C, but not PL-D, in HN2 kappa 24 cells, whereas PL-D, but not PL-C, was stimulated following such treatment of CHO kappa 18 cells. Our results using the model neuronal system, HN2 kappa 24, demonstrate cell-type specific, positive coupling of the kappa opioid receptor to the major Ca2+ mobilizing system, the PL-C cascade, which regulates neuronal firing.

Adenylyl Cyclases↗
PubMed1996

Induction of the serotonin1A receptor in neuronal cells during prolonged stress and degeneration.

Neuronal migration in brain is followed by differentiation of committed neurons and simultaneous apoptosis of uncommitted preneuronal cells due to a limiting supply of trophic factors and nutrients. We have dissected differentiation and apoptosis by designing a simple in vitro model for this nutrient deprivation using engineered neuronal cell lines stably transfected with a promoterless segment (G-21) of the intronless human serotonin1A receptor (5-HT1A-R) gene. Despite the use of widely different heterologous promoters (cytomegalovirus and Rous sarcoma virus) for the stable expression of G-21, a dramatic increase in expression of the 5-HT(1A)-R (five- to 15-fold) and its mRNA was always observed during degeneration and apoptosis of nutrient-deprived neuronal cells. Involvement in this induction of a 170-bp 5'-end untranslated sequence (5'-UT) (tail end of the 500-bp natural promoter) of G-21 was confirmed by stable transfection of neuronal cells with an SV-40 promoter-driven construct harboring the 5'-UT and the reporter chloramphenicol acetyltransferase (CAT) cDNA. Presence of the 5'-UT resulted in a threefold increase in CAT expression during nutrient deprivation in randomly chosen clones. The induction was also observed in the endogenous 5-HT1A-R, expressed by embryonic day 16 mouse hippocampal neurons, subsequent to nutrient deprivation and onset of degeneration. A trophic role of the 5-HT1A-R has been suggested in earlier studies. Considering the example of protective heat shock proteins, which are induced during various types of stress, our results suggest that stressed neuronal cells undergoing degeneration and apoptosis synthesize increased levels of 5-HT1A-R as a final attempt to survive.

Animals↗
PubMed1996

Effect of pentoxifylline on the course of systemic Candida albicans infection in mice.

Pentoxifylline can decrease the production of tumour necrosis factor alpha (TNF alpha) by endotoxin-stimulated macrophages and may improve survival in animals with overwhelming bacterial sepsis. In this study various doses of pentoxifylline were administered to mice with systemic Candida albicans infection to determine its effect on serum TNF alpha levels, organ fungal burden, and host survival. Intraperitoneal injections of pentoxifylline at 20 mg/kg every 8 h did not affect these endpoints. However, fungal counts were significantly higher in kidneys of animals that received 30 and 60 mg/kg of pentoxifylline every 8 h when compared to controls. Injection of 60 mg/kg of pentoxifylline at 8 h intervals also significantly shortened mean survival from 5.8 to 3.8 days (P = 0.01). Pentoxifylline did not affect peripheral WBC counts, serum TNF alpha and interleukin-6 levels, or the density of neutrophils in tissues. In vitro, pentoxifylline decreased the production of TNF alpha by C. albicans-stimulated macrophages in a dose-dependent manner, but only at concentrations greater than 100 mg/L. In contrast, pentoxifylline suppressed TNF alpha production by endotoxin-stimulated macrophages at concentrations as low as 10 mg/L. Thus, higher doses of pentoxifylline are detrimental in systemic C. albicans infection. However, the detrimental effect is not mediated by alterations in serum TNF alpha or interleukin-6 levels or the aggregation of neutrophils in tissues.

Animals↗
PubMed1995

Occurrence of haemagglutination-inhibition antibodies against egg drop syndrome 1976 virus in broilers.

From a total of 22 broiler flocks 347 serum samples were screened by the haemagglutination inhibition (HI) test and 114 (32.9%) were positive for antibodies to egg drop syndrome 1976 (EDS'76). The HI titres of the serum samples ranged from 2 to 9 log2 and the overall geometric mean titre was 3.9 log2. Of the serum samples 82.5% showed HI titres between 2(2) to 2(5) and the most frequent titre was 2(3). All the flocks were positive and the flock prevalence of HI antibodies ranged from 13.3 to 46.6 per cent. The age distribution of HI antibodies and their titres have also been recorded. The widespread prevalence of EDS'76 virus infection in broilers and its likely significance are discussed.

Adenoviridae↗
PubMed1995

Fluconazole and amphotericin B antifungal therapies do not negate the protective effect of endogenous tumor necrosis factor in a murine model of fatal disseminated candidiasis.

In systemic candidiasis, endogenously produced tumor necrosis factor (TNF)-alpha prolongs survival of the infected host. To determine whether endogenously produced TNF-alpha has a beneficial effect beyond that provided by antifungal therapy, survival was assessed in infected mice that received fluconazole or amphotericin B alone and in combination with anti-TNF-alpha antibody. Neutralization of serum TNF-alpha did not affect survival in fluconazole recipients; however, for amphotericin B recipients, it significantly shortened mean survival. For both fluconazole and amphotericin B recipients, colony counts in organs were significantly higher in animals that also received anti-TNF-alpha antibody. Administration of anti-TNF-alpha antibody with amphotericin B or fluconazole did not affect the morphology of fungi or the inflammatory response in kidneys. This study suggests that exogenous TNF-alpha and drugs that increase the endogenous production of TNF-alpha by the host may be useful adjuncts to fluconazole and amphotericin B for the treatment of systemic candidiasis.

Amphotericin B↗
PubMed1994

Tumor necrosis factor alpha has a protective role in a murine model of systemic candidiasis.

The role of tumor necrosis factor alpha (TNF-alpha) in host defense against systemic Candida albicans infection was evaluated in a murine model of systemic candidiasis in which uniform death occurred between 5 and 6 days after infection. TNF-alpha was first detected at 16 h postinfection and progressively increased thereafter. Peak levels (700 to 900 pg/ml) were measured in mice near death. Administration of 0.5 to 1.0 mg of polyclonal immunoglobulin G (IgG) TNF-alpha antibody (TNF-alpha Ab) to mice 2 h preinfection neutralized serum TNF-alpha for up to 30 h. However, this regimen shortened survival from a mean of 5.5 days for IgG controls to 3.4 days (P = 1.9 x 10(-12)). Semiquantitative cultures of spleen, lung, liver, and kidney conducted at 1, 2, and 3 days postinfection found colony counts of spleen and kidney to be significantly higher for TNF-alpha Ab recipients but only for the first 48 h. Administration of 1.5 and 1.0 mg of TNF-alpha Ab at 2 h before and 48 h after fungal injection, respectively, shortened the mean survival from 4.9 to 2.3 days (P = 5.2 x 10(-8)). This regimen neutralized serum TNF-alpha throughout infection. With this regimen, colony counts of all organs were significantly higher in TNF-alpha Ab recipients at 1, 2, and 3 days postinfection. Histopathologic studies showed an increase in the number and size of C. albicans foci in tissues. Peripheral leukocyte counts and inflammatory response in tissue were similar for TNF-alpha Ab and IgG sham recipients. In vitro, incubation of C. albicans with four to eight times the peak serum levels of TNF-alpha for up to 24 h did not inhibit the rate of germ tube or pseudohypha formation. Thus, TNF-alpha that was produced during infection with C. albicans augmented host resistance against this organism and prolonged survival. The protective effect of TNF-alpha was not mediated by increased leukocytes in blood or tissues nor by a direct anticandidal effect of TNF-alpha. This study suggests that the administration of exogenous TNF-alpha may enhance host resistance against systemic C. albicans infection and may improve host survival.

Animals↗
PubMed1993

The extraction and assay of substance P in the rat sciatic nerve.

Published data for substance P (SP) content of sciatic nerves in control rats vary greatly. This study sought possible reasons for this variability by examining the influence of homogenisation procedures, freezing and selection of left/right nerve or proximal/distal segments. Substance P-like immunoreactivity (SP-LI) content (pg/mg nerve protein +/- SD) was significantly greater in sciatic nerves which had been homogenised using motor-powered equipment (615.4 +/- 146.3) as opposed to a hand-held pestle (445.4 +/- 111.8). Our second investigation revealed that freshly homogenised nerve tissue yielded greater SP-LI (508.8 +/- 88.7) than either tissue snap frozen in liquid nitrogen (307.6 +/- 77.9), snap-frozen and stored at -70 degrees C for 7 days (331.8 +/- 53.5), or tissue allowed to remain in the cadaver for 1 h and subsequently dissected and homogenised immediately (412.6 +/- 105.8). These data also show that storage at -70 degrees C imposes no further losses on those caused by freezing and extraction of frozen tissue. Two further studies indicated no variation between left and right sciatic nerves nor any proximal-distal gradients. Hence, this study illuminated the need for samples to be homogenised using motor-powered equipment immediately upon dissection, followed by SP extraction, for complete avoidance of losses of SP-LI.

Animals↗