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Biomedical subjects

K Sharma

Publications and source records attributed to K Sharma.

At least 73 records · Page 4Linked to original sources
PubMed1998

Quantitative estimates of ABH secretion in saliva of human twins.

Blood and saliva samples of 122 like-sexed twin pairs (65 MZ and 57 DZ) living in Chandigarh (India) were analyzed for ABH polymorphism. The results indicated that ABH secretions were independent of ABO blood groups though there was an indication of higher incidence of non-secretors among 'O' blood group twin individuals. No significant differences were observed between twins and singletons in secretor gene frequency estimates. The quantitative data revealed that mean titre scores for H substances were lower than that for A and B substances. F test contrasting intra-pair variance between zygosities for ABH quantitative secretions was highly significant indicating stronger genetic component of variation. The results suggested that quantitative assay of ABH secretions would be a better indicator for zygosity determination than mere qualitative differentiation.

ABO Blood-Group System↗
PubMed1998

Sex differences in genetic determinants of craniofacial variations--a study based on twin kinships.

Race, sex, nutritional status and cultural factors affect craniofacial morphogenesis. Out of these, sex is a major factor in craniofacial differentiation, because it can be stronger in one ethnic group and weaker in another. In this study, sex differences in genetic variance and heritability of 13 craniofacial traits are investigated. The study is based on a sample of 45 MZ and 101 DZ twin pairs and their 125 singleton siblings, 104 fathers and 103 mothers in 146 families drawn from an urban population of Chandigarh. Results of t-tests for equality of the means reveal association of zygosity with the mean value of bigonial diameter in female twins and for none in males. Heterogeneity of variance is observed in about 50% traits in females as compared to 15% in males. This invalidates conventional within-pair genetic variance estimates for these traits. The revised genetic variance ratios are higher on an average in males than in females. However, there is greater MZ environmental covariance in male twins than their female counterparts. Family data indicate higher maternal effect for ear height, nasal height and frontal breadth, while greater paternal effect is seen in cranial traits. Sex-wise midparent-child regression coefficients show greater heritability in daughters for nasal traits and bigonial breadth, while sons show higher genetic component for head size measures.

Adult↗
PubMed1998

Transcriptional activation of transforming growth factor-beta1 in mesangial cell culture by high glucose concentration.

BACKGROUND: Transforming growth factor-beta (TGF-beta) is an important hypertrophic and prosclerotic cytokine in the pathogenesis of diabetic nephropathy. The mechanisms of regulation of the TGF-beta system by high ambient glucose in kidney cells are incompletely defined. This study examined the mechanisms of regulation of TGF-beta1 expression by high glucose in murine mesangial cells (MMCs) in culture. METHODS: MMCs were cultured in either normal (100 mg/dl) or high (450 mg/dl) D-glucose concentration. Total TGF-beta1 protein secretion and bioactivity, mRNA expression and stability, and gene transcription rate were measured; promoter-reporter chloramphenicol acetyltransferase (CAT) assays and electrophoretic mobility shift assay (EMSA) were performed to investigate the presence of putative glucose-response elements. RESULTS: Raising the ambient D-glucose concentration for 72 hours increased TGF-beta1 bioactivity in cell culture medium by 47% and total TGF-beta1 secretion by approximately 90%. Northern analysis demonstrated that the steady-state TGF-beta1 mRNA level was increased nearly twofold after 48 hours of growth in high glucose. This increase was not due to increased stability, as the half-life of the message was approximately five hours in both normal and high glucose conditions. Transcriptional activity of the TGF-beta1 gene (nuclear run-on assay) was increased by 73% in cells grown in high glucose for 24 hours. Transiently transfected MMCs with CAT constructs containing varying lengths of the murine TGF-beta1 promoter demonstrated that high glucose selectively increased the expression of only one of the constructs, pA835. Sequence inspection revealed the presence of a putative glucose responsive element, CACGTG, within this construct. High glucose in MMC culture for 24 hours increased nuclear protein binding to a probe containing this element when analyzed using EMSA. CONCLUSIONS: High glucose stimulates total TGF-beta1 protein production and bioactivity as well as the steady-state level of TGF-beta1 mRNA. The latter effect is due primarily to stimulation of gene transcription rate rather than message stability. Transcriptional activation by high glucose may involve a region in the TGF-beta1 promoter containing a putative glucose-response element.

Animals↗
PubMed1998

The Ob protein (leptin) and the kidney.

Mutation of the Ob gene, which encodes for leptin, or mutation of the leptin receptor leads to obesity in mice. Humans, for the most part, have a positive correlation of leptin with body fat mass suggesting possible defects in leptin effector mechanisms that may contribute to obesity. As patients on hemodialysis have difficulty with appetite, we investigated whether leptin is cleared by the kidney and is elevated in hemodialysis patients. In patients with intact renal function there was a net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there was no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal disease (ESRD), peripheral leptin levels factored for body mass index was increased by fourfold as compared to a group of healthy controls (N = 338). The leptin receptor exists in a long and short form, with the long form primarily expressed in the hypothalamus but also in the lungs and kidneys of the mouse. Further studies are necessary to clarify the role of leptin in regulating appetite in patients with ESRD and the role of leptin in directly affecting kidney function via its receptors.

Animals↗
PubMed1998

Potential role of TGF-beta in diabetic nephropathy.

Renal injury in diabetes mellitus is a major cause of morbidity and mortality. Several manifestations of diabetic nephropathy may be a consequence of altered production and/or response to cytokines or growth factors. Transforming growth factor-beta (TGF-beta) is one such factor because it promotes renal cell hypertrophy and regulates the production of extracellular matrix molecules. In addition, high ambient glucose increases TGF-beta1 mRNA and protein level in cultured proximal tubular cells and glomerular epithelial and mesangial cells. Neutralizing anti-TGF-beta antibodies or antisense TGF-beta1 oligodeoxynucleotides prevents the hypertrophic effects of high glucose and the stimulation of matrix synthesis in renal cells. Several reports have described overexpression of TGF-beta in the glomeruli and tubulointerstitium of experimental and human diabetes mellitus. We recently provided evidence that the kidney in diabetic patients displays net renal production of immunoreactive TGF-beta1, whereas there is net renal extraction in nondiabetic subjects. We also demonstrated that short-term treatment of streptozotocin-diabetic mice with neutralizing monoclonal antibody directed against TGF-beta significantly reduces kidney weight and glomerular hypertrophy, and attenuates the increase in extracellular matrix mRNA levels. The factors that mediate increased renal TGF-beta activity involve hyperglycemia per se and the intermediary action of other potent mediators such as angiotensin II, thromboxane, endothelins, and platelet-derived growth factor.

Animals↗
PubMed1998

A comparison of artificial saliva and pilocarpine in the management of xerostomia in patients with advanced cancer.

This was a crossover study comparing a mucin-based artificial saliva (Saliva Orthana) and pilocarpine hydrochloride (Salagen) in the management of xerostomia in patients with advanced cancer. The pilocarpine was found to be more effective than the artificial saliva in terms of mean change in visual analogue scale scores for xerostomia (P = 0.003). Furthermore, more patients reported that it had helped their xerostomia, and more patients wanted to continue with it after the study. However, the pilocarpine was found to be associated with more side-effects than the artificial saliva (P < 0.001). These side-effects were usually reported as being mild. Of the patients who used both treatments, 50% preferred the artificial saliva, and 50% preferred the pilocarpine. The commonest reason for preferring the artificial saliva was the fact that it was a spray, rather than a tablet.

Adult↗
PubMed1998

Formation of Rathke's pouch requires dual induction from the diencephalon.

Targeted disruption of the homeobox gene T/ebp (Nkx2.1, Ttf1, Titf1) in mice results in ablation of the pituitary. Paradoxically, while T/ebp is expressed in the ventral diencephalon during forebrain formation, it is not expressed in Rathke's pouch or in the pituitary gland at any time of embryogenesis. Examination of pituitary development in the T/ebp homozygous null mutant embryos revealed that a pouch rudiment is initially formed but is eliminated by programmed cell death before formation of a definitive pouch. In the diencephalon of the mutant, Bmp4 expression is maintained, whereas Fgf8 expression is not detectable. These data and additional genetic and molecular observations suggest that Rathke's pouch develops in a two-step process that requires at least two sequential inductive signals from the diencephalon. First, BMP4 is required for induction and formation of the pouch rudiment, a role confirmed by analysis of Bmp4 homozygous null mutant embryos. Second, FGF8 is necessary for activation of the key regulatory gene Lhx3 and subsequent development of the pouch rudiment into a definitive pouch. This study provides firm molecular genetic evidence that morphogenesis of the pituitary primordium is induced in vivo by signals from the adjacent diencephalon.

Animals↗
PubMed1998

Sensory axons are guided by local cues in the developing dorsal spinal cord.

During development, different classes of sensory neurons establish distinctive central projections within the spinal cord. Muscle spindle afferents (Ia fibers) grow ventrally through the dorsal horn to the ventral cord, whereas cutaneous sensory collaterals remain confined to the dorsal horn. We have studied the nature of the cues used by Ia fibers in establishing their characteristic projections within the dorsal horn. An organotypic culture preparation of embryonic chicken spinal cord and sensory ganglia was used to test the influence of ventral spinal cord and local cues within the dorsal spinal cord on the growing Ia afferents. When the ventral half of the spinal cord was replaced with an inverted duplicate dorsal half, Ia fibers entering through the dorsal columns still grew ventrally within the host dorsal horn. After the fibers entered the duplicate dorsal half, they continued growing in the same direction. With respect to the duplicate dorsal tissue, this was in an opposite, ventral-to-dorsal, direction. In both cases, however, Ia collaterals remained confined to the medial dorsal laminae. Restriction to these laminae was maintained even when the fibers had to change their direction of growth to stay within them. These results show that cues from the ventral cord are not required for the development of correct Ia projections within the dorsal horn. Local, rather than long-range directional, cues appear to determine the pattern of these projections. When the ventral half of the spinal cord was left intact but sensory axons were forced to enter the dorsal gray matter growing rostrally or caudally, their collateral axons grew in random directions, further showing the absence of directional cues even when the ventral cord was present. Taken together, these observations suggest that Ia fibers are guided by local positional cues that keep them confined to the medial gray matter within the dorsal horn, but their direction of growth is determined primarily by their orientation and position as they enter the dorsal gray matter.

Afferent Pathways↗
PubMed1997

Transforming growth factor-beta1 inhibits type I inositol 1,4,5-trisphosphate receptor expression and enhances its phosphorylation in mesangial cells.

A potentially important cross-talk characteristic of transforming growth factor-beta (TGF-beta) is to inhibit platelet-derived growth factor-induced intracellular calcium rise (Baffy, G., Sharma, K., Shi, W., Ziyadeh, F. N., and Williamson, J. R. (1995) Biochem. Biophys. Res. Commun. 210, 378-383) in murine mesangial cells. The present study examined the possible basis for this effect by evaluating the regulation of the type I inositol 1,4,5-trisphosphate receptor (IP3R) by TGF-beta. TGF-beta1 down-regulates IP3R protein expression by >90% with maximal and half-maximal effects after 8 and 2 h, respectively. TGF-beta1 also decreased IP3R mRNA expression by 59% after 1 h. Phosphorylation of the IP3R was also demonstrated as early as 15 min after TGF-beta1 exposure. Back phosphorylation assays of IP3R from TGF-beta1-treated mesangial cells with protein kinase A (PKA), indicated that TGF-beta1-induced phosphorylation of the IP3R occurs at similar sites as for PKA. In vitro kinase assays using the known IP3R peptide substrates for PKA, RPSGRRESLTSFGNP and ARRDSVLAAS, demonstrated that TGF-beta1 induces phosphorylation of both peptides (158 and 123% of control values, respectively). TGF-beta1-induced phosphorylation was prevented by the addition of the PKA inhibitor peptide in the in vitro kinase assay. It is proposed that TGF-beta-mediated effects on the IP3R may be an important characteristic of its ability to modulate the response of cells to factors that employ IP3R-mediated calcium release.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Mex67p, a novel factor for nuclear mRNA export, binds to both poly(A)+ RNA and nuclear pores.

An essential cellular factor for nuclear mRNA export called Mex67p which has homologous proteins in human and Caenorhabditis elegans was identified through its genetic interaction with nucleoporin Nup85p. In the thermosensitive mex67-5 mutant, poly(A)+ RNA accumulates in intranuclear foci shortly after shift to the restrictive temperature, but NLS-mediated nuclear protein import is not inhibited. In vivo, Mex67p tagged with green fluorescent protein (GFP) is found at the nuclear pores, but mutant mex67-5-GFP accumulates in the cytoplasm. Upon purification of poly(A)+ RNA derived from of UV-irradiated yeast cells, Mex67p, but not nucleoporins Nup85p and Nup57p, was crosslinked to mRNA. In a two-hybrid screen, a putative RNA-binding protein with RNP consensus motifs was found to interact with the Mex67p carboxy-terminal domain. Thus, Mex67p is likely to participate directly in the export of mRNA from the nucleus to the cytoplasm.

Amino Acid Sequence↗
PubMed1997

Selective involvement of basal ganglia and occipital cortex in a patient with acute endosulfan poisoning.

We report a teenage girl with acute endosulfan poisoning who developed psychosis, generalized tonic-clonic seizures, myoclonic jerks, cortical blindness and limb rigidity. Serial magnetic resonance imaging (MRI) showed bilateral reversible lesions localized to caudate nucleus, putamen and occipital cortex; internal capsule and thalamus were spared. This selective involvement may have a bearing on mechanisms underlying endosulfan toxicity.

Adolescent↗
PubMed1997

"Cyclodiode". Trans-scleral diode laser cyclophotocoagulation in the treatment of advanced refractory glaucoma.

PURPOSE: To analyze the results of intraocular pressure (IOP) reduction by diode laser contact cyclophotocoagulation ("cyclodiode") in cases of advanced glaucoma refractory to alternative treatments. METHODS: Two hundred and ten eyes of 195 patients, ages 1 to 89 years (mean, 51 years) were followed for 3 to 30 months (mean, 10 months) after cyclodiode treatment. RESULTS: More than one treatment was given in 102 eyes (49%), and the overall mean number of treatments given per eye was 1.75 (range, 2-5). Mean pretreatment IOP was 34.1 mmHg (+/-10.6 mmHg). At last follow-up, mean IOP was 20.1 mmHg (+/-9.3 mmHg), and mean total medications was reduced from 2.3 to 1.7. Mean final IOP was lowest in patients with silicone oil glaucoma (17.3 mmHg), and the mean reduction in IOP was greatest in patients with neovascular glaucoma (23.9 mmHg). At last follow-up, visual acuity was worse than before treatment in 29% of eyes, unchanged in 60%, and better in 11%. Overall success rate (IOP < 22 mmHg) was 66% at a mean follow-up of 10 months. Phthisis occurred in one eye (0.5%), and chronic hypotony (0 mmHg < IOP < 5 mmHg for > 3 months) in a further two eyes (1%). Corneal graft decompensation followed treatment in two eyes, macular pucker occurred in one eye, and combined hyphema/vitreous hemorrhage in one patient. CONCLUSIONS: Diode laser cycloablation is relatively safe and effective at controlling IOP in eyes with advanced refractory glaucoma in the short and medium term. With the treatment parameters used, multiple applications may be needed.

Adolescent↗
PubMed1997

Prevalence and correlates of susceptibility to motion sickness.

Data on susceptibility to motion sickness were collected on a sample of 535 individuals divided into eight groups. The prevalence of motion sickness among Tibetans and Northeast Indians (28%) was slightly higher than Northwest Indians (26%). Generally speaking, females (27.3%) were more susceptible than males (16.8%). Among different groups, the highest incidence of susceptibility to motion sickness (SMS) was recorded in schizophrenic patients (30%), while the lowest in rowers (zero percent). Ears and eyes are the most potent receptors of provocative motion that causes sickness. Individuals with greater spatial and motor control, reflected in sports like rowing, athletics and professions like armed and paramilitary forces, were less susceptible to motion sickness. The SMS was significantly higher in individuals who suffered from spatial disorientation (35.05%), migraine (26.31%), gastrointestinal disorders (26.82%) and those who were more sensitive to unpleasant odours (24.64%) and preferred sweet flavours (24.48%) than their counterparts. These correlates have been utilized to explain the genesis of sickness using threshold model. Genetic and environmental pathways are strongly advocated. Past episodes of motion sickness acted as a strong psychological attribute in determining further episodes. The roadway buses and trucks proved more effective passive transportation types that caused sickness. The voluntary stabilization of the head and neck movements and gaze control proved very effective natural measures adopted by 38% subjects to avoid or limit motion sickness. About 50% of susceptible individuals became less susceptible or fully acclimatized to motion sickness due to habituation. The mean age at acclimatization was 21.98 +/- 5.93 years.

Adaptation, Physiological↗
PubMed1997

The twinning rates and epidemiological characteristics of births in southeast Uttar Pradesh, India.

Birth statistics over a period of 5 years were analyzed to study epidemiological characteristics of twinning in Southeast Uttar Pradesh, India. The data revealed higher incidence of breech twins (11.84% of all cotwins) as compared to breech single births (2.18%). But the perinatal mortality and caesarean section rates were similar in both twin and singleton pregnancies. The cumulative twinning rate over the studied period was 11.70 per 1000 live births. The MZ and DZ twinning rates were estimated respectively as 3.67 and 8.03 per mill. The mean maternal age of sampled mothers was 26.42 years with one standard deviation of 5.30 years. The twinning rate for mothers over 35 years of age was about four times higher than that in mothers younger than 20 years. Incidentally, the twinning rate was the highest at parity four and a non-linear curve could more appropriately be fitted to the series of data. Seasonal variations were observed for both twin and singleton births. The highest frequency of births was observed from August through October. But seasonal index for twinning rate showed a clear bimodal distribution with peaks in April (223) and September (167).

Adult↗
PubMed1997

Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.

Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.

Aged↗
PubMed1997

Surgery or palliation for hip fractures in patients with advanced malignancy?

OBJECTIVE: to investigate the management and outcome of patients with advanced cancer who sustain fractures of the neck of femur. DESIGN: multi-centre, prospective, observational study. SUBJECTS: patients with advanced malignancy, under the care of a palliative care team, who subsequently fractured a femur. OUTCOME MEASURES: survival time post-fracture, return home. RESULTS: 40 patients were recruited with a fractured neck of femur. Analysis of the management of patients according to the Eastern Co-operative Oncology Group performance score was undertaken. Twenty-nine patients were treated surgically and 11 conservatively. For patients with performance scores of 0, 1 and 2 surgery usually resulted in a successful rehabilitation outcome and discharge. None of those with scores of 3 or 4 returned home. CONCLUSION: patients with advanced malignancy and a poor performance score should not be automatically referred for surgery.

Aged↗
PubMed1997

Wound botulism associated with black tar heroin.

The incidence of wound botulism is increasing and the epidemiology of the disease is changing. The majority of new cases are associated with injection drug use, in particular, the use of Mexican black tar heroin. This case report and discussion of wound botulism illustrate the following important points: Dysphagia, dysphonia, diplopia, and descending paralysis, in association with injection drug use, should alert the treating physician to the possibility of wound botulism. In such patients, the onset of respiratory failure may be sudden and without clinically obvious signs of respiratory weakness. For the reported patient, maximum inspiratory force measurements were the only reliable indicator of respiratory muscle weakness. This is a measurement not routinely performed in the ED, but may prove essential for patients with suspected wound botulism. To minimize the effect of the botulinum toxin and to decrease length of hospital stay, antitoxin administration and surgical wound debridement should be performed early.

Botulism↗