Biomedical subjects

J Singh

Publications and source records attributed to J Singh.

At least 235 records · Page 13Linked to original sources

PubMed1998

Dietary fish oil inhibits the expression of farnesyl protein transferase and colon tumor development in rodents.

Although epidemiological and experimental studies indicate a strong relationship between different dietary fats and risk of colon cancer, the modulating effects of these nutritional factors at the molecular level are not fully elucidated. Activated ras genes have been implicated in the etiology of many human malignancies, including colon cancer. It is well established that the transforming ability of ras-p21 depends on its correct localization in plasma membrane. We have previously demonstrated that ingestion of a relatively higher amount of dietary fish oil leads to reduced plasma membrane levels of ras-p21 with concomitant increase in its cytoplasmic contents during the promotion and progression phases of chemically-induced colon tumorigenesis. In this follow-up experiment, we have found that intake of a high amount of corn oil, one of the most widely used fats in the American diet, enhances the expression of farnesyl protein transferase (FPTase). This enzyme catalyses farnesylation of ras precursors in a critical step during post-translational modification of ras oncoproteins, thereby enabling their anchorage to plasma membrane. In contrast, consumption of high amounts of fish oil, which is rich in omega-3 polyunsaturated fatty acids, reduces the levels of FPTase expression, thus inhibiting post-translational processing of ras precursors resulting in decreased ras function both in colonic mucosa as well as in colon tumors. These results correlate with increased incidence and multiplicity of grossly visibly colon tumors in carcinogen-treated animals fed a high corn oil diet versus decreased incidence and multiplicity of colon tumors in their counterparts fed the high fish oil diet. This dietary inhibition of FPTase may have a practical chemopreventive potential.

Alkyl and Aryl Transferases↗

PubMed1998

Epidemiologic consequences of moderate coverage levels of measles vaccine in a district headquarter town (Alwar) in India, 1996.

This paper describes the epidemiology of measles in a medium size town (population 240,000) in India where vaccine coverage levels have remained constant at around 70 per cent in the past 7 years. A retrospective community survey covering 4023 children under 10 years old detected 252 cases of measles in the previous year. This gave an annual incidence of 6.3 per cent (95 per cent CI 5.5-7). About half of the cases occurred in vaccinated children. Only 5 per cent of the cases occurred in children below 9 months of age. This age is appropriate for routine measles immunization. Despite modest coverage levels with only 54 per cent effective vaccine (estimated by a screening method), there was a modest upward shift in the age distribution of measles cases; the median age was more than 48 months.

Age Distribution↗

PubMed1998

Immunohistochemical distribution of follistatin in dominant and subordinate follicles and the corpus luteum of cattle.

The study was done to quantitatively characterize the distribution of follistatin in ovarian follicles and corpora lutea at specific stages of development. Transrectal ultrasonography was used to monitor the growth of individually identified follicles from 2 days before ovulation until the day of ovariectomy on Day 3 of wave 1 (n = 8), Day 6 of wave 1 (n = 6), Day 1 of wave 2 (n = 6), or after onset of proestrus, at least 17 days postovulation (n = 7). Days of ovariectomy represent the growing, early-static, late-static, and regressing phases of the dominant follicle of wave 1, respectively. Subordinate (n = 24), preselection (n = 15), and preovulatory (n = 6) follicles and corpora lutea (n = 31) were also analyzed. Follistatin was localized using immunohistochemical labeling of paraffin sections, and relative amounts were quantitated using densitometric analysis. Follistatin was distributed in the perinuclear cytoplasm of granulosa and luteal cells but not in theca cells. Dominant follicles contained more (p < 0.05) follistatin than corresponding subordinate follicles. The amount of follistatin was maximal during the mid-growing phase of the dominant follicle and decreased thereafter (p < 0.05). Among the corpora lutea, the maximal amount was detected at mid-diestrus (Day 11 postovulation). Less than half of luteal cells displayed the stain for follistatin; positively stained luteal cells were located in close proximity to blood capillaries. Follistatin was not detectable in the corpus luteum during metestrus (Day 3 postovulation) or proestrus (Day >/= 17 postovulation). In summary, the degree of immunohistochemical expression of follistatin was phase specific for both follicles and corpora lutea. The most intense staining in follicles was associated with the period of functional dominance and in corpora lutea was seen during the phase of maximal development. Significant phase-related differences in follistatin expression provide rationale for the hypothesis that follistatin is involved in the final stages of follicle and luteal gland development in cattle.

Animals↗

PubMed1998

Wegener's granulomatosis in a patient with apparent drug-induced acute interstitial nephritis.

We describe a patient whose clinical presentation was suggestive of drug-induced acute interstitial nephritis (AIN). A renal biopsy and serologic testing led instead to the diagnosis of Wegener's granulomatosis (WG) with necrotizing crescentic glomerulonephritis. Treatment with corticosteroids and cyclophosphamide resulted initially in complete recovery of renal function, and an exacerbation of acute renal failure after doses of these agents had been tapered responded to resumption of the original regimen. We report this case to emphasize the potentially identical presentations of AIN and WG. Since the two conditions are treated differently, we suggest that the diagnosis of AIN should be accepted only after biopsy confirmation.

Acute Disease↗

PubMed1998

Medical decision-making and the patient: understanding preference patterns for growth hormone therapy using conjoint analysis.

OBJECTIVES: This study examines two questions that relate to patients' role in medical decision making: (1) Do patients utilize multiple attributes in evaluating different treatment options?, and (2) Do patient treatment preferences evidence heterogeneity and disparate patterns? Although research has examined these questions by using either individual- or aggregate-level approaches, the authors demonstrate an intermediate level approach (ie, relating to patient subgroups). METHODS: The authors utilize growth augmentation therapy (GAT) as a context for analyzing these questions because GAT reflects a class of nonemergency treatments that (1) are based on genetic technology, (2) aim to improve the quality (rather than quantity) of life, and (3) offer useful insights for the patient's role in medical decision making. Using conjoint analysis, a methodology especially suited for the study of patient-consumer preferences but largely unexplored in the medical field, data were obtained from 154 parents for their decision to pursue GAT for their child. RESULTS: In all, six attributes were utilized to study GAT, including risk of long-term side effects (1:10,000 or 1:100,000), certainty of effect (50% or 100% of cases), amount of effect (1-2 inches or 4-5 inches in adult height), out-of-pocket cost ($100, $2,000, or $10,000/year) and child's attitude (likes or not likes therapy). An experimental design using conjoint analysis procedures revealed five preference patterns that reflect clear disparities in the importance that parents attach to the different attributes of growth therapy. These preference patterns are (1) child-focused (23%), (2) risk-conscious (36%), (3) balanced (23%), (4) cost-conscious (14%), and (5) ease-of-use (4%) oriented. Additional tests provided evidence for the validity of these preference patterns. Finally, this preference heterogeneity related systematically to parental characteristics (eg, demographic, psychologic). CONCLUSIONS: The study results offer additional insights into medical decision making with the consumer as the focal point and extend previous work that has tended to emphasize either an individual- or aggregate-based analysis. Implications for researchers and health care delivery in general and growth hormone management in particular are provided.

Adult↗

PubMed1998

Patient and hospital characteristics associated with patient assessments of hospital obstetrical care.

OBJECTIVES: The goals of this study were to examine the relationship of patient assessments of hospital care with patient and hospital characteristics. In addition, the authors sought to assess relationships between patient assessments and other patient-derived measures of care (eg, how much they were helped by the hospitalization and amount of pain experienced). METHODS: The authors surveyed 16,051 women (response rate, 58%) discharged after labor and delivery from 18 hospitals during the study period of 1992 to 1994. Patient assessments were obtained using a previously validated survey instrument, Patient Judgment of Hospital Quality, that includes eight scales assessing different aspects of the process of care (eg, physician care, discharge procedures) and other single item assessments (eg, overall quality). For this study, we utilized five of the scales (physician care, nursing care, information, discharge preparation, global assessments [willingness to brag, recommend or return to the hospital]). For analysis, items were rated on a five-point ordinal scale from poor to excellent. For scoring purposes, responses were transformed to linear ratings, ranging from 0 to 100 (eg, 0 = poor care, 100 = excellent care). RESULTS: In multivariable analyses, the authors found that patients who were older, white, not married, uninsured or had commercial insurance, and in better health status were significantly more likely to give higher assessments (P < 0.01), although very little of the variance in assessment scores was explained by these characteristics (2%-3%). In bivariate analyses, patient assessments were higher in nonteaching hospitals and those with fewer beds, fewer deliveries, lower cesarean-section (C-section) rates, fewer patients with Medicaid, and higher rates of vaginal births after C-section deliveries. When these variables were utilized as independent predictors in multivariable analyses using adjusted nested linear regression (to account for clustering of patients), few of the hospital characteristics reached a level of statistical significance. Finally, correlations between the five scales and other patient assessments of quality, such as how much they were helped by the hospitalization, were statistically significant (P < 0.01) and high in magnitude, ranging from 0.47 to 0.61. CONCLUSIONS: Although hospital scores differed according to several patient and hospital characteristics, the magnitude of the associations was relatively small. The findings suggest that, with respect to obstetric care, patient assessments may represent a robust measure that can be applied to diverse hospitals and patient casemix.

Adolescent↗

PubMed1998

A novel function of the DNA repair gene rhp6 in mating-type silencing by chromatin remodeling in fission yeast.

Recent studies have indicated that the DNA replication machinery is coupled to silencing of mating-type loci in the budding yeast Saccharomyces cerevisiae, and a similar silencing mechanism may operate in the distantly related yeast Schizosaccharomyces pombe. Regarding gene regulation, an important function of DNA replication may be in coupling of faithful chromatin assembly to reestablishment of the parental states of gene expression in daughter cells. We have been interested in isolating mutants that are defective in this hypothesized coupling. An S. pombe mutant fortuitously isolated from a screen for temperature-sensitive growth and silencing phenotype exhibited a novel defect in silencing that was dependent on the switching competence of the mating-type loci, a property that differentiates this mutant from other silencing mutants of S. pombe as well as of S. cerevisiae. This unique mutant phenotype defined a locus which we named sng1 (for silencing not governed). Chromatin analysis revealed a switching-dependent unfolding of the donor loci mat2P and mat3M in the sng1(-) mutant, as indicated by increased accessibility to the in vivo-expressed Escherichia coli dam methylase. Unexpectedly, cloning and sequencing identified the gene as the previously isolated DNA repair gene rhp6. RAD6, an rhp6 homolog in S. cerevisiae, is required for postreplication DNA repair and ubiquitination of histones H2A and H2B. This study implicates the Rad6/rhp6 protein in gene regulation and, more importantly, suggests that a transient window of opportunity exists to ensure the remodeling of chromatin structure during chromosome replication and recombination. We propose that the effects of the sng1(-)/rhp6(-) mutation on silencing are indirect consequences of changes in chromatin structure.

Chromatin↗

PubMed1998

Lipophilic versus hydrophilic beta(1) blockers and the cardiac sympatho-vagal balance during stress and daily activity in patients after acute myocardial infarction.

OBJECTIVE: To compare the effects of a lipophilic and a hydrophilic beta(1) blocker on cardiac sympatho-vagal balance during daytime activity and stress in patients four to six weeks after myocardial infarction. DESIGN: Randomised, double blind, crossover study comparing the effect of atenolol (50 mg once daily) with metoprolol CR (100 mg once daily) with treatment periods of four weeks. SETTING: Large teaching hospital. PATIENTS: 50 patients (45 male, 5 female, age range 40 to 75 years), four to six weeks after an acute myocardial infarction. METHODS: At the end of each treatment period the 24 hour heart rate variability, heart rate variability power spectra during head up tilt and mental stress, baroreflex sensitivity, and exercise performance were evaluated. RESULTS: During daytime activity and during orthostatic and mental stress, both heart rate and the ratio between the low and high frequency spectral components of the heart rate variability were significantly lower with atenolol. Conversely, there was no difference between treatments in baroreflex sensitivity and resting plasma catecholamines. Exercise duration and peak oxygen consumption did not differ between treatments, but the heart rate during submaximal and peak exercise was significantly lower with atenolol. CONCLUSIONS: At the doses used in this study, atenolol achieved greater beta(1) adrenergic blockade than metoprolol CR and this was associated with significant inhibition of vagal withdrawal during stress. This suggests that peripheral blockade of beta(1) adrenergic receptors may be more important than central blockade in preventing stress induced vagal withdrawal in patients after myocardial infarction.

Adrenergic beta-Antagonists↗

PubMed1998

Ultrasound image attributes of bovine ovarian follicles and endocrine and functional correlates.

Heifers were studied to determine whether computer-assisted quantitative echotexture analysis of ultrasound images reflect functional and endocrine characteristics of dominant and subordinate follicles at specific stages of development. Heifers were examined using transrectal ultrasonography each day until ovariectomy on day 3 (n = 8) and day 6 (n = 9) of wave 1, day 1 of wave 2 (n = 7), or after onset of pro-oestrus > or = days after ovulation (n = 8) to obtain growing, early-static, late-static and regressing dominant follicles of wave 1, subordinate follicles, preselection follicles and preovulatory dominant follicles. Ultrasound images of the follicles were obtained in vitro and analysed using custom-developed computer algorithms. Mean pixel (picture element) values (grey-scale: black = 0, white = 255) for the follicle wall and stroma increased (P < 0.05) progressively from the growing to the regressing phases of the dominant follicle of wave 1. The antrum and wall of subordinate follicles had higher (P < 0.05) mean pixel values than that of the corresponding dominant follicles. Pixel heterogeneity (a measure of variation of grey-scale values of pixels) of images of the follicle antrum and wall increased (P < 0.05) progressively during the early-static to regressing phases. A progressive increase (P < 0.05) in the slope of the regression line of pixel values for the follicle wall was detected from the growing to the regressing phases of the dominant follicle of wave 1. The regression line of the wall of the preovulatory dominant follicle had the lowest (P < 0.05) slope. Oestradiol concentration in the follicular fluid decreased (P < 0.05) from the growing to the late-static phase, while a marked decrease (P < 0.05) in the androstenedione concentration was recorded between the growing and the early-static phases of the dominant follicle. Progesterone content did not increase until follicles were in the final stages of regression. Pixel heterogeneity of the antrum and wall, and the slope of the follicle wall regression line were negatively correlated (P < 0.001) with oestradiol and the oestradiol:progesterone ratio in follicular fluid. The results of this study support the hypothesis that echotexture characteristics of ultrasound images of the follicle antrum and wall are correlated with the functional and endocrine status of a follicle.

Androstenedione↗

PubMed1998

Effects of islet hormones on nerve-mediated and acetylcholine-evoked secretory responses in the isolated pancreas of normal and diabetic rats.

This study employs the pancreas of normal and diabetic rats to investigate the relationship between the endocrine and exocrine pancreas in the control of exocrine secretion employing enzyme and immunohistochemical and physiological techniques. Acetylcholine esterase (ACh-E) positive nerves were distributed in the interacinar regions of the pancreas lying close to the exocrine cells. There was no difference between the cholinergic innervation of the pancreas in normal and diabetic rat. Insulin (INS) immunopositive cells were observed in the peripheral and central portions of the Islet of Langerhans in the pancreas of normal rat. In the diabetic animals the number of INS-positive cells were decreased. In contrast, glucagon (GLU) and somatostatin (SOM)-immunopositive cells were identified mainly in the peripheral parts of the Islets of Langerhans and their numbers increased markedly in the diabetic pancreas. Insulin alone had no significant effect on amylase secretion in the normal pancreas whereas GLU and SOM evoked small increases in amylase out compared to basal. In contrast, the islet hormones have no detectable secretory effect on the diabetic pancreas compared to control. Both electrical field stimulation (EFS) of intrinsic secretomotor nerves and exogenous application of acetylcholine (ACh) resulted in marked increases in amylase secretion. In pancreatic acini and acinar cells ACh evoked dose-dependent increases in amylase release. In normal pancreatic segments a combination of either INS or GLU with EFS or ACh resulted in marked potentiation of amylase output. In contrast, SOM inhibited the EFS-evoked amylase output but enhanced the secretory response to ACh. In pancreatic acini and acinar cells from normal rat and in pancreatic segments from diabetic rats, the islet hormones had no potentiating effect on the ACh-evoked secretory response. Similarly, in the diabetic rat the islet hormone had no effect on EFS-evoked amylase output. In fura-2 loaded pancreatic acinar cells ACh-induced a marked increase in intracellular free calcium concentration [Ca2+]i compared to basal. Either INS or GLU, but not SOM, elicited a small increase in [Ca2+]i. Combining either INS or GLU with ACh resulted in a potentiation of [Ca2+]i compared with ACh alone. In contrast, SOM had no significant effect on the ACh-induced [Ca2+]i compared to the response obtained with ACh alone. In pancreatic acinar cells of diabetic rat ACh-elicited similar magnitude of [Ca2+]i compared to acinar cells of normal rat. However, when the islet hormones were combined with ACh there was no enhancement of [Ca2+]i compared to ACh alone. The results indicate that the potentiation of either EFS or ACh-evoked secretory responses by the islet hormones seem to occur only in pancreatic segments which have intact viable Islets of Langerhans and not in either acini and acinar cells or from the pancreas of diabetic rat. Moreover, it is apparent that cellular Ca2+ is involved with the interaction of ACh with either INS or GLU.

Acetylcholine↗

PubMed1998

Identification of a Frizzled-like cysteine rich domain in the extracellular region of developmental receptor tyrosine kinases.

In Drosophila, members of the Frizzled family of tissue-polarity genes encode proteins that appear to function as cell-surface receptors for Wnts. The Frizzled genes belong to the seven transmembrane class of receptors (7TMR) and have on their extracellular region a cysteine-rich domain that has been implicated as the Wnt binding domain. This region has a characteristic spacing of ten cysteines, which has also been identified in FrzB (a secreted antagonist of Wnt signaling) and Smoothened (another 7TMR, which is involved in the hedgehog signalling pathway). We have identified, using BLAST, sequence similarity between the cysteine-rich domain of Frizzled and several receptor tyrosine kinases, which have roles in development. These include the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. At present, the ligands for these developmental tyrosine kinases are unknown. Our results suggest that Wnt-like ligands may bind to these developmental tyrosine kinases

Amino Acid Sequence↗

PubMed1998

Transplacental transfer of measles antibody in Delhi.

OBJECTIVE: To find out the patterns of and the factors, if any, affecting the transplacental transfer of measles antibody. DESIGN: Comparison of measles antibody titres in mothers with titres in cord blood samples. METHODS: Maternal and cord blood samples from 174 full-term pregnant women of middle socio-economic status were tested for hemagglutination inhibition (HI) antibody against measles in Delhi during October 1993 to January 1995. None of the mothers had been immunized against measles. RESULTS: Antibody were undetectable in both maternal and cord samples in only 4 (2.3%) pairs. Mean maternal titre was found to be 2.94 Log2. Transplacental concentration and dilution were respectively observed in 34% and 26% of the samples. Cord titres were more often higher than the maternal values only if the maternal values were low. Overall, cord/maternal ratio of mean titre (Log2) was found to be 1.06. Although the age of the mother and parity had had no significant bearing on the transplacental transfer of measles antibody, cord titres were significantly more often higher than the maternal values as the birth weight increased (Chi-square for linear trend = 5.4; p = 0.02). CONCLUSIONS: The study failed to show appreciable concentration of measles antibodies across the placenta.

Adolescent↗

PubMed1998

Carotid artery dissection presenting as a painless Horner's syndrome in a pilot: fit to fly?

We describe a case of a middle-aged Caucasian pilot who presented to us with a painless left Horner's syndrome due to a focal dissection of the infra-petrous portion of the ipsilateral internal carotid artery. He did not suffer symptoms of cerebral ischemia at the time of onset, or during the following 2 yr. The Horner's syndrome persisted unchanged throughout follow-up. Serial magnetic resonance angiograms showed some regression of the focal stenosis at 12 mo, with no further change over the next 10 mo. The literature suggests that the risk of stroke after onset of dissection is usually in the first month, and the risk of recurrence of dissection is about 1% per year after the first year. Our patient was prescribed aspirin 300 mg.d-1, and certified to fly as or with a co-pilot commencing 1 yr after onset of his symptoms.

Aerospace Medicine↗

PubMed1998

A study on opportunistic enteric parasites in 80 HIV seropositive patients.

AIDS is characteristically associated with several opportunistic enteric protozoal infestations that cause chronic and at times fatal diarrhoeas. A study is undertaken to isolated opportunistic enteric parasites in 80 HIV seropositive patients. An attempt is made to correlate and signify the presence of coexistent oral candidosis and enteric pathogens.

AIDS-Related Opportunistic Infections↗

PubMed1998

Outbreak of viral hepatitis B in a rural community in India linked to inadequately sterilized needles and syringes.

In India, virtually all outbreaks of viral hepatitis are considered to be due to faeco-orally transmitted hepatitis E virus. Recently, a cluster of 15 cases of viral hepatitis B was found in three villages in Gujarat State. The cases were epidemiologically linked to the use of inadequately sterilized needles and syringes by a local unqualified medical practitioner. The outbreak evolved slowly over a period of 3 months and was marked by a high case fatality rate (46.7%), probably because of concurrent infection with hepatitis D virus (HDV) or sexually transmitted infections. But for the many fatalities within 2-3 weeks of the onset of illness, the outbreak would have gone unnoticed. The findings emphasize the importance of inadequately sterilized needles and syringes in the transmission of viral hepatitis B in India, the need to strengthen the routine surveillance system, and to organize an education campaign targeting all health care workers including private practitioners, especially those working in rural areas, as well as the public at large, to take all possible measures to prevent this often fatal infection.

Adult↗

PubMed1998

Coronary artery bypass grafting without cardiopulmonary bypass.

Coronary artery bypass surgery on a beating heart is now an accepted modality to treat selected patients of ischaemic heart disease. From June '92 through Sep '97, 162 patients underwent this procedure. There was no mortality and none of the patients had any respiratory or neurological morbidity, though 24% of the patients form a high risk group for conventional coronary bypass surgery. It is definitely cost effective in comparison to any other modalities for treatment of ischaemic heart disease. We conclude that continous use of this technique is justified and all cardiac surgeons should have exposure to this procedure.

Adult↗

PubMed1998

Acute sporadic viral hepatitis in urban population of a tribal district in Madhya Pradesh.

OBJECTIVE: To estimate the incidence of acute sporadic viral hepatitis and describe its epidemiology in an urban population. DESIGN: A retrospective community survey for jaundice cases. SETTING: Headquarter town of a tribal district, Bastar, in Madhya Pradesh state, India. METHOD: Trained paramedics surveyed about 51,643 population to detect cases of jaundice which occurred in the past one year. Cases were examined to collect clinical and epidemiological data. blood samples were drawn from all cases who had jaundice in the past 3 months for testing them for markers of viral hepatitis. RESULTS: Study estimated the annual incidence of jaundice cases as 244 (95% CI 201-287) per 100,000 population. Almost 95% jaundice cases occurred in summer and monsoon months. People from all socio-economic strata were affected. The incidence of jaundice was found to be the highest in children below 15 years of age (3.7 per 1000) which declined significantly with the increase in age (p = 0.0000). The overall incidence in two sexes was not different statistically (p = 0.7). Of 57 cases who had jaundice in the past 3 months, 19 (33%) were confirmed as having viral hepatitis. Hepatitis A and E combined together contributed 68% (13/19) of acute sporadic cases of viral hepatitis, whereas hepatitis B, C and D accounted for the remaining 32% of the cases. CONCLUSION: The study found the annual incidence of laboratory supported cases of viral hepatitis to be 81 (95 CI 57-106) per 100,000 population, which suggests that it is an important public health problem in India. Hepatitis A was much more prevalent than hepatitis E. Etiology of almost two-thirds of jaundice cases could not be established which require further community studies.

Acute Disease↗

PubMed1998

Assay of carcinogenicity of tobacco metabolites employing microsomal degranulation technique.

Carcinogenicity of salivarty extracts of different types of tobaccos smoked and chewed in India and Pan Parag were tested using microsomal degranulation technique. Results obtained on the basis of RNA/protein ratios (Indices to confirm the detachment of ribosomes from microsomes) showed that tobaccos used for cigarette, bidi, hukah and chewing tobacco with lime as well as Pan Parag were positively carcinogenic. Two fractions out of 7 isolated chromatographically from salivary extract of chewing tobacco plus lime were found to be carcinogenic. Elemental and spectral analyses indicated that the fractions are possibly an aromatic compound with an aliphatic side chain and N-(buty1 nitrosamine)-1-(3-pyridyl)-4-hydroxy-1-butanone.

Animals↗