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Biomedical subjects

J Singh

Publications and source records attributed to J Singh.

At least 271 records · Page 15Linked to original sources

Effect of penetration enhancers and iontophoresis on the ultrastructure and cholecystokinin-8 permeability through porcine skin.

The present study explores the effect of chemical penetration enhancers and iontophoresis on the in vitro permeability of cholecystokinin-8 (CCK-8) through porcine epidermis and on the ultrastructural changes in stratum corneum as observed by transmission electron microscopy (TEM). Enhancer [i.e., ethanol (EtOH), and 10% oleic acid in combination with ethanol (OA/EtOH)] pretreatment significantly increased (p < 0.01) the permeability coefficient of CCK-8 in comparison with the control (pretreated epidermis without enhancer). Iontophoresis further increased the permeability of CCK-8 (p < 0.01) through the enhancer-pretreated epidermis in comparison with the control. These results showed the synergistic effect of iontophoresis and enhancers such as OA/EtOH that provides an additional driving force to maintain and control the target flux of CCK-8. The ultrastructure of stratum corneum treated with ethanol demonstrated a loss of structural components in the superficial stratum corneum cell layers. OA/EtOH transformed the highly compact cells of stratum corneum into a looser network of filaments, creating an increased free volume and greater intracellular surface area. Treatment of stratum corneum with OA/EtOH followed by iontophoresis resulted in further swelling of stratum corneum cell layers. In conclusion, OA/EtOH in combination with iontophoresis increased the permeability of CCK-8 by loosening and swelling of stratum corneum cell layers.

Animals↗

Receptor-'Ck' dependent signalling regulates the LDL-receptor gene transcription.

Evidence of a novel receptor, having affinity for cholesterol in lipoproteins and intrinsic tyrosine kinase activity (designated as Receptor 'Ck') prompted us to explore its role in LDL-dependent transcriptional regulation of apoprotein-B specific LDL receptor gene in human lymphocytes. The results of this study revealed that LDL dependent activation of this Receptor 'Ck' was essential for the regulation of apoprotein-B specific LDL receptor gene transcription. Further, by using various blockers of as well as simulating the Receptor 'Ck'-dependent signalling in human lymphocytes, we were able to show that Receptor 'Ck'-dependent signalling was involved in the LDL-dependent transcriptional regulation of 160 kDa apoprotein B specific LDL receptor gene. Based upon these results, we conclude that cholesterol derived from LDL. catabolism within the cell does not have any role in the transcriptional regulation of apoprotein B specific LDL receptor gene.

Apolipoproteins B↗

RNA-mediated regulation of Receptor-Ck gene in human platelets.

The study addressed to understand the regulation of Receptor-'Ck' gene at the translational level revealed that exogenous cholesterol has the inherent capacity to regulate the endogenous synthesis of Receptor-'Ck' by initiating intracellular targeting of the Receptor-'Ck' to the mRNP pool within human platelets and this effect could be reversed when the platelets were incubated with cholesterol coupled with either dB cAMP or dB cGMP. Based upon these observations, we propose that Receptor-'Ck' initiated signalling, which involves second messengers like PA, cAMP and cGMP, may be responsible for the autoregulation of Receptor-'Ck' gene expression at the translational level.

Blood Platelets↗

Intact mirror-tracing and impaired rotary-pursuit skill learning in patients with Huntington's disease: evidence for dissociable memory systems in skill learning.

Skill learning in early-stage Huntington's disease (HD) patients was compared with that of normal controls on 2 perceptual-motor tasks, rotary pursuit and mirror tracing. HD patients demonstrated a dissociation between impaired rotary-pursuit and intact mirror-tracing skill learning. These results suggest that different forms of perceptual-motor skill learning are mediated by separable neural circuits. A striatal memory system may be essential for sequence or open-loop skill learning but not for skills that involve the closed-loop learning of novel visual-response mappings. It is hypothesized that working memory deficits in HD resulting from frontostriatal damage may account broadly for intact and impaired long-term learning and memory in HD patients.

Adult↗

Bifidobacterium longum, a lactic acid-producing intestinal bacterium inhibits colon cancer and modulates the intermediate biomarkers of colon carcinogenesis.

The human colon can be described as a complex microbial ecosystem, comprising several hundred bacterial species. Some of these enteric bacteria are beneficial to the host and have been shown to exert antimutagenic and anticarcinogenic properties. We have investigated the colon tumor inhibitory activity of Bifidobacterium longum, a lactic acid-producing enterobacterium. The modifying effects of this lactic culture on colonic mucosal and/or tumor cell proliferation, ODC activity and ras-p21 oncoprotein expression in colon carcinogenesis were also analyzed. Male F344 rats were fed a modified AIN-76A diet containing 0 or 2% lyophilized cultures of B. longum and s.c. administered azoxymethane (AOM) dissolved in normal saline at a dose of 15 mg/kg body wt, once weekly for 2 weeks. Vehicle controls received an equal volume of normal saline s.c. Animals were maintained on control or experimental diets until termination of the study. Animals intended for analysis of cell proliferation were killed 20 weeks after the second AOM injection, whereas animals intended for colon tumor analysis and measurement of ODC activity and ras-p21 expression were killed 40 weeks after the last AOM injection. The data demonstrate that dietary administration of lyophilized cultures of B. longum resulted in significant suppression of colon tumor incidence and tumor multiplicity and also reduced tumor volume. Results also revealed that ingestion of B. longum significantly inhibited AOM-induced cell proliferation, ODC activity and expression of ras-p21 oncoprotein. Data suggest that oral administration of probiotic B. longum exerts strong antitumor activity, as indicated by modulation of the intermediate biomarkers of colon cancer, and consequently reduced tumor outcome.

Animals↗

Solid-phase extraction of THC metabolite from urine using the Empore disk cartridge prior to analysis by GC-MS.

The Empore disk cartridges (C18) were evaluated for sample preparation in the gas chromatography-mass spectrometry confirmational assay for the 11-nor-9-carboxy-delta 9-tetrahydro-cannabinol (THCCOOH) metabolite. The performance of the Empore disk cartridges, determined by the recovery, precision, limit of detection (LOD), and limit of quantitation (LOQ) of the assay was comparable with the performance of a widely used solid-phase extraction cartridge (Spec C18 cartridges) and the traditional liquid-liquid extraction technique. The Empore disk cartridges showed an average recovery of 89% at low concentrations of 6 ng/mL of the THC metabolite spiked into urine. The recovery was consistent across three different lots of Empore disk cartridges. The within-run precision of the assay at a concentration of 18 ng/mL had a coefficient of variation of 2%, and the LOD and LOQ were determined to be 1 ng/mL.

Dronabinol↗

Epidemiological considerations of the age distribution of measles in India: a review.

This paper reviews the Indian data on age distribution of measles prior to large scale immunization. In metropolitan areas, the median age was about 24 months and virtually all the cases were recorded in children under 5, whereas median age in most of rural studies was < 4-< 5 years and all the persons were not affected until 10 years of age. The situation was in between in other areas. Since less than 10 per cent of the cases occurred before 9 months of age, this age is appropriate for routine measles immunization. The results also suggested the choice of age groups to be immunized during measles mass campaigns; the upper age may be 3 years in metropolitan city, 10 years in rural areas, and 5 years in the rest of the population.

Age Distribution↗

Transplacental dilution of tetanus antitoxins in Delhi.

Maternal blood-cord samples from 171 women of middle socio-economic status who had been administered at least two doses of tetanus toxoid (TT), were assayed for tetanus antitoxins by passive haemagglutination (PHA) test. All the mother as well as cord samples had antitoxin titres > or = 0.015IU/ml, the generally accepted minimal protective level; 98 per cent of the mothers and 97 per cent of the newborns had levels > or = 0.125IU/ml. Transplacental dilution was observed in 45 per cent of the samples; the cord/maternal antitoxin ratio (C/M) of geometric mean titre (GMT) was found to be 0.72. The C/M ratio was not affected by the maternal age, parity, birth weight, and number of TT doses administered to mother. The study showed that tetanus antitoxins were diluted on the fetal side of circulation, but the protective levels of antitoxins were achieved in all the newborns as the mothers had received at least two doses of TT before delivery.

Adolescent↗

Acetylcholine-evoked potassium transport in the isolated guinea-pig pancreas.

In this study, K+ concentration was measured in effluent samples from superfused guinea-pig pancreatic pieces in control conditions and during stimulation with ACh, employing the technique of flame photometry. ACh (10(-7)-10(-5) M) evoked a dose-dependent and sustained increase in K+ concentration in the effluent (K+ release). The removal of Ca2+ from the superfusing medium and the addition of 10(-4) M EGTA caused a significant (P < 0.05) reduction in the ACh-evoked K+ efflux. Replacement of extracellular Cl- in the superfusing physiological salt solution with NO3- abolished the ACh-induced K+ efflux. In contrast, when Cl- was replaced with Br-, ACh still evoked marked K+ release. Pretreatment of pancreatic segments with the loop diuretic furosemide (10(-4) M) resulted in an inhibition of K+ efflux elicited by ACh. Stimulation of pancreatic segments with the Na(+)-K(+)-ATPase inhibitor ouabain (10(-3) M) caused a large efflux of K+. In the continuous presence of ouabain, ACh application elicited no further change in the K+ release. The results indicate that ACh-evoked K+ release from guinea-pig pancreatic segments is sensitive to ouabain, Cl-, furosemide and extracellular Ca2+ and that only the basal efflux is augmented by ouabain. The findings provide further evidence that a diuretic-sensitive coupled Na(+)-K(+)-Cl- cotransport system operates in the guinea-pig pancreas, as it does in other similar transporting epithelia, to bring about K+ mobilization.

Acetylcholine↗

Expression of SSEA-1 (Lewis(x)) on transitional cell carcinoma of the bladder.

The expression of stage-specific embryonic antigen 1 (SSEA-1) in transitional cell carcinomas of the bladder (TCCB) has been reported to correlate with tumor grade and the likelihood of lymphatic metastases. We examined the expression of this antigen in TCCBs to evaluate if staining correlated with grade, stage, recurrence, progression and response to intravesical chemotherapy. We studied the expression of SSEA-1 in TCCBs from 74 patients by staining with two different monoclonal antibodies (Mabs), P-12 and anti-SSEA-1, to evaluate if staining correlated with grade, stage and tumor recurrence. Staining was considered as positive or negative irrespective of the intensity of staining. Extent of tumor staining was measured in quartiles of 100% (25, 50, 75 and 100). Follow-up was available in 47/74 (63%) patients and ranged from 6 months to 13 years (median 2 years). Staining with one or both Mabs was observed in 57/75 (76%) tumors. None of the grade I tumors showed > 50% staining while 26% of grade II and only 33% of grade III tumors showed staining of > 50% of cells. 21% of patients whose tumors showed staining with both Mabs were free of recurrence after resection of the primary tumor; 41% of patients with tumors staining negative with both Mabs showed no recurrence. Expression of SSEA-1 does correlate with tumor recurrence especially in grade II tumors, but the correlation is not very strong (0.05 < p < 0.1). Expression of this antigen is a weak indicator of recurrence in superficial TCCBs.

Aged↗

Ultrasound image attributes of the bovine corpus luteum: structural and functional correlates.

Nulliparous heifers (n = 58) were studied to determine whether computer-assisted quantitative echotexture analysis of ultrasound images reflects the functional and histomorphological characteristics of the corpus luteum. The ovaries of heifers were examined daily by transrectal ultrasonography from day -2 (day 0 = ovulation) until the day of ovariectomy during metoestrus (day 3; n = 8), early dioestrus (day 6; n = 9), mid-dioestrus (mean, day 10; n = 7), or pro-oestrus (mean, day 18; n = 8; Expt 1). High resolution ultrasound images of corpora lutea were obtained in vitro, and were digitized and analysed using custom-developed computer algorithms optimized for ultrasonography. Cryostat sections of corpora lutea were examined for lipid distribution, and corpora lutea were homogenized to determine the content of progesterone, total protein, cholesterol and triglyceride. In Expt 2, heifers (n = 26) were ovariectomized as in Expt 1, and ovaries were prepared for histomorphometric evaluation. Pixel values (brightness of picture elements) of ultrasound images of corpora lutea were characterized as high during metoestrus, low during early and mid-dioestrus, and increasing again during pro-oestrus (P < 0.05). Changes (P < 0.001) in volume density of luteal cells were characterized as increasing from metoestrus (40.7 +/- 0.4%) to mid-dioestrus (55.8 +/- 2.8%) and decreasing again at pro-oestrus (41.5 +/- 0.9%). The proportion of blood vascular components decreased (P < 0.001) progressively from 31.0 +/- 1.0% in metoestrus to 15.6 +/- 1.1% in pro-oestrus. Pixel values of ultrasound images of corpora lutea were correlated with luteal (r = -0.72, P < 0.05) and plasma (r = -0.71, P < 0.03) progesterone concentration, and to the volume densities of luteal cells (r = -0.75, P < 0.02) and connective tissue (r = 0.69, P < 0.03). Estimates of triglyceride, protein and cholesterol content of corpora lutea were not correlated with pixel values of ultrasound images. Protein and cholesterol content did not change while triglyceride concentration increased during pro-oestrus (P < 0.05). Results support the hypothesis that ultrasound images reflect luteal and plasma progesterone content, and histomorphological characteristics of the corpus luteum.

Algorithms↗

Genotypes of Japanese encephalitis virus isolated in three states in Malaysia.

Two hundred forty nucleotides from the pre-membrane gene region of 12 Japanese encephalitis virus (JEV) strains isolated from three different regions of Malaysia from 1993 to 1994 were sequenced and compared with each other and with the JEV strains from different geographic areas in Asia. These 12 Malaysian isolates were classified into two genotypes. The four JEV strains isolated from Sarawak in 1994 and the four JEV strains isolated from Sepang, Selangor in 1993 were classified into one genotype that included earlier isolated strains from Malaysia (JE-827 from Sarawak in 1968 and WTP/70/22 from Kuala Lumpur in 1970). The four JEV strains from Ipoh, Perak in 1994 were classified into another genotype that included JEV strains isolated from northern Thailand and Cambodia. In an earlier report, 10 JEV strains from Sabak Bernam, Selangor in 1992 were classified into the largest genotype that included strains isolated in temperate regions such as Japan, China, and Taiwan. The data indicate that at least three genotypes of JEV have been circulating in Malaysia.

Amino Acid Sequence↗

Ultrastructural changes of macroglial cells in the rat brain following an exposure to a non-penetrative blast.

The present study examined the ultrastructural changes in astrocytes and oligodendrocytes in rats following an exposure to a non-penetrative blast. At 1 and 7 days after the blast, the astrocytes in the cerebral and cerebellar cortex were hypertrophied; their end-feet associated with the blood vessels were also swollen, bearing sparsely distributed organelles. The above changes were not observed in experimental rats when the survival interval was prolonged. It is concluded from this study that the blast could have disrupted the integrity of the blood-brain barrier resulting in possible abnormal entry of serum-derived substances thereby leading to astrocytic hypertrophy. The reversible nature of the changes is evidenced by the seemingly normal appearance of astrocytes in rats killed at 14, 21 and 28 days after the blast. Oligodendrocytes remained unaffected at various time intervals after the blast.

Animals↗

Effect of aspartate and glutamate on nociception, catalepsy and core temperature in rats.

Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU altered the tail flick reaction time to thermal stimulation in a dose dependent manner, increasing it with low doses and reduced with high doses. Naloxone (10 micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic effect. These EAAs also antagonized catalepsy induced by haloperidol, chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a hyperthermic response in all animals, including those in which hypothermia was induced by reserpine. These EAAs produced a comparable central modulatory effects on nociception, catalepsy and core temperature.

Adrenergic Uptake Inhibitors↗

Measles vaccine efficacy in India: a review.

Different workers have used different designs to assess effectiveness of live, further attenuated measles vaccine i.e., seroconversion studies, outbreak investigations, field trials and coverage survey methods. The results were often contradictory. We reanalyzed data from these studies to find out optimum vaccine efficacy (VE) and its determinants in the Indian context. Although nutritional status and sex of the subjects did not affect seroconversion rates, the rates were greater among initially seronegative and older children. Overall seroconversion rates in 9-11 months children ranged between 56 and 96%. Studies showing poor seroconversion had an inadequate sample size and/or technical flaws that detracted from the reliability of results. However, appropriately designed studies demonstrated seroconversion rates of more than 90% in 9-11 months children who were initially seronegative. Since 5-10% of 9-11 months old infants had persistent measles maternal antibody, measles vaccine may be around 85-90% effective in this age group. These results are in agreement with the findings observed in outbreak investigations. These outbreaks fulfilled all the criteria which are considered necessary for optimum estimation of VE in such settings; VE was found to be more than 90% in outbreak settings. Conversely, retrospective coverage surveys grossly under estimated VE (about 60%) which was probably due to misclassification of vaccination status of enrolled children. The surveys were undertaken in areas where immunization records were grossly incomplete and only few mothers retained immunization cards. Unfortunately, VE was also under estimated in field trials which were neither randomized nor blind, and no placebo injections were used in control children; many observations were on record which could explain the under estimation of VE. Reanalysis of data from different types of studies indicates that efficacy of measles vaccine given at 9-11 months of age is of the order of 85-90% in the Indian context.

Child, Preschool↗

Vibrio cholerae O1 and O139 in less than five years old children hospitalised for watery diarrhoea in Delhi, 1993.

In Delhi, patients with cholera-like illness are admitted to the Infectious Diseases Hospital. In 1993, rectal swabs from 836 such patients aged less than five years were examined for the presence of Vibrio cholerae O1 and O139. Of them, 232 (28%), 180 (22%), and 424 (51%) were found suffering from O1 cholera, O139 cholera, and non-cholera watery diarrhoea respectively. Twelve children (1.4%) excreted both V. cholerae O1 and O139. Both types of cholera were similarly distributed by age, with 19% of the cases occurring in infants. The findings indicate that cholera should be suspected in children aged less than two years and in infants with acute watery diarrhoea. For both serotypes, males were more represented than females; the differences were, however, not significant. Clinical features of patients with V. cholerae O139 and O1 were indistinguishable, except that a significantly higher percentage of the former had fever. Potential risk factors for cholera were almost equally prevalent in the families of children aged less than 5 years having either O1 or O139 cholera. The results suggest a similar mode of transmission of the two serotypes in children. By inference, the preventive and control measures are also likely to be similar.

Antigens, Bacterial↗

Sensitivity of neonatal tetanus surveillance system in India.

OBJECTIVE: To estimate the sensitivity of neonatal tetanus (NNT) surveillance in India. DESIGN: A comparison of two sets of data obtained from NNT mortality surveys and routine surveillance system. METHODS: NNT mortality surveys were undertaken in 1981, 1989 and 1992 using 30 cluster sampling technique. The data on reported incidence of NNT through routine surveillance system was taken from the published documents of Health Ministry and WHO. RESULTS: In 1981, the incidence of disease in a national survey was estimated to be 4 and 16.4 per 1000 live births in urban and rural areas, respectively. Follow up surveys in 1989 and 1992 estimated the overall incidence as 4 and 1.74 per 1000 live births, respectively. Comparing the reported and estimated by surveys, around 10% of NNT cases were reported. CONCLUSIONS: There is an urgent need to strengthen the routine surveillance system which at present grossly under-reports the NNT incidence in India.

Humans↗