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Biomedical subjects

A Gupta

Publications and source records attributed to A Gupta.

At least 199 records · Page 11Linked to original sources
PubMed2001

Incidence and effects of Ha-ras codon 12 G-->A transition mutations in preneoplastic lesions induced by N-nitrosomethylbenzylamine in the rat esophagus.

N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis is an important model for squamous cell carcinoma of the human esophagus. In this model, previous studies have shown that the GGA-->GAA Ha-ras codon 12 mutation is present in the majority of papillomas. No other Ha-ras mutation has been identified. Studies using other models of chemical carcinogenesis suggest that Ha-ras activation has a critical role during tumor initiation. We have used laser-capture microdissection and polymerase chain reaction-restriction fragment length polymorphism analysis to study the role of codon 12 Ha-ras mutation at various stages of tumor development in the rat esophagus. Our results indicate that Ha-ras mutation was present infrequently (4.3%) in premalignant lesions. The incidence of Ha-ras mutation was high in papillomas (57.1%), however, and 50% of papillomas expressed mutant Ha-ras RNA message. Additionally, there was a linear trend correlating increased incidence of Ha-ras mutation with later papilloma stage. These data suggest the role of ras activation later in neoplastic development. To evaluate the potential mechanism of action by which Ha-ras contributes to promotion and progression in this model, we compared mRNA expression of cyclin D1 and p27 in Ha-ras mutant and Ha-ras normal papillomas. We found no differences in mRNA expression of either cyclin D1 or p27 between these two papilloma populations. Our data suggest an important paradigm shift for the role of ras mutations in this model of chemical carcinogenesis, indicating a functional role of Ha-ras activation in promotion/progression and not in the initiation phase of NMBA-induced papillomagenesis.

Animals↗
PubMed2001

Evolutionary changes in dopaminergic modulation of courtship behavior in Cnemidophorus whiptail lizards.

Preoptic dopamine release is integral to the display of copulatory behaviors in male mammals and birds. However, while the anatomical distributions of the dopamine synthesizing enzyme tyrosine hydroxylase are similar among vertebrates, evolutionary changes in the functional role of dopamine are poorly understood. In this study, we tested whether a dopamine D1 receptor agonist would facilitate the display of courtship and copulatory behaviors in two related Cnemidophorine lizards (Cnemidophorus inornatus and Cnemidophorus uniparens). Cnemidophorus lizards offer a unique system to study evolutionary changes in functionality because ancestral (e.g., C. inornatus) and descendant (e.g., C. uniparens) species can be studied in parallel. Cnemidophorus uniparens is an all-female, parthenogenetic species and is the triploid descendant of the sexual and diploid species C. inornatus. Here we report that in castrated male C. inornatus and ovariectomized C. uniparens a dopamine D1 agonist increased the proportion of individuals mounting and decreased the latency to mount. Moreover, there was a species difference in sensitivity to the agonist: Mounting was elicited at a lower dose in C. uniparens than in C. inornatus. One possible explanation for this heightened sensitivity in the triploid parthenogen is that, by virtue of the increased ploidy, the parthenogen has elevated levels of D1 receptor in limbic brain areas modulating courtship behavior.

Animals↗
PubMed2001

Gag-derived proteins of HIV-1 isolates from Indian patients: cloning, expression, and purification of p17 of B- and C-subtypes.

A simple and efficient method for expression in Escherichia coli and purification of matrix protein, p17, of human immunodeficiency virus type 1 (HIV-1) of both B- and C-subtypes is described. DNA sequences encoding p17 of B- and C-subtype were cloned from respective gag sequences. The gag sequences were obtained by PCR amplification using DNA extracted from peripheral blood lymphocytes of an HIV-1 infected patient from India. A T7-promoter-based expression system was optimized for expression of p17 in soluble form. p17 (B- and C-subtype) was purified to near homogeneity using conventional chromatographic techniques. Purification of p17 (C-subtype) is described for the first time with yield of 7.7 mg from a 1-liter culture. The yield of p17 (B-subtype) is 14.7 mg from a 1-liter culture, which is severalfold better than that reported earlier. N-terminal sequencing and CD spectra of the purified proteins, p17B and p17C, show that the proteins are properly processed and well-folded. The immunoreactivity of both types of p17 to sera from HIV-infected individuals is comparable.

Amino Acid Sequence↗
PubMed2001

Functional magnetic resonance imaging of the primary motor cortex in humans: response to increased functional demands.

Functional magnetic resonance imaging (fMRI) studies have been performed on 20 right handed volunteers at 1.5 Tesla using echo planar imaging (EPI) protocol. Index finger tapping invoked localized activation in the primary motor area. Consistent and highly reproducible activation in the primary motor area was observed in six different sessions of a volunteer over a period of one month. Increased tapping rate resulted in increase in the blood oxygenation level dependent (BOLD) signal intensity as well as the volume/area of activation (pixels) in the contralateral primary motor area up to tapping rate of 120 taps/min (2 Hz), beyond which it saturates. Activation in supplementary motor area was also observed. The obtained results are correlated to increased functional demands.

Adult↗
PubMed2001

G protein coupled receptor dimerization: implications in modulating receptor function.

Protein-protein interactions are involved in the regulation of a large number of biological processes. It is well established that a variety of cell surface receptors interact with each other to form dimers, and that this is essential for their activation. Although the existence of G protein coupled receptor dimers was predicted from early pharmacological and biochemical analysis, solid evidence supporting dimerization has come within the past few years following the cloning of G protein coupled receptor cDNAs. Using differential epitope tagging and selective immunoisolation of receptor complexes, dimerization of a number of G protein coupled receptors including members of the rhodopsin, secretin, and metabotropic glutamate receptor families have been reported. More recently fluorescence or bioluminescence resonance energy transfer techniques have been used to examine dimerization of these receptors in live cells. These studies have found that whereas in some cases there is an agonist induced increase in the level of dimers, in others there is a decrease or no change in dimer levels. Several recent studies have also reported the ability of related members of G protein coupled receptors to heterodimerize. These heterodimers exhibit distinct physical and functional properties. Examination of possible sites of interactions between receptors has implicated a role for extracellular, transmembrane and/or C-terminal region in dimerization. The functional consequences of dimerization, explored mainly using mutant receptors, have demonstrated a role in modulating agonist affinity, efficacy, and/or trafficking properties. Thus dimerization appears to be a universal phenomenon that provides an additional mechanism for modulation of receptor function as well as cross-talk between G protein coupled receptors.

Animals↗
PubMed2001

Spectrum of adolescent-onset nephrotic syndrome in Indian children.

There are few data regarding adolescent-onset nephrotic syndrome (NS) and no guidelines for biopsy criteria and treatment protocol. This study was conducted to analyze the clinical spectrum of adolescent-onset NS and evaluate possible biopsy criteria in these children. A prospective analysis was carried out on all patients with idiopathic NS (fulfilling the ISKDC criteria) with onset between 1 and 18 years of age. They were evaluated clinically, followed by biochemical investigations and kidney biopsy. These characteristics of patients with onset between 1 and 12 years (group A) were compared with the same parameters in patients with onset between 12 and 18 years of age (group B) referred to our hospital over the same period. Among all clinical parameters, microhematuria was significantly more prevalent in adolescents (P<0.001). Kidney biopsy was performed in 88% of adolescent patients. Focal segmental glomerulosclerosis (FSGS) was the most-common histopathology in group B (46.3%) compared with minimal change disease (MCD) in group A (42.9%). Group B had a significantly higher frequency of membranoproliferative glomerulonephritis (MPGN) (P<0.005) and a significantly lower frequency of MCD (P<0.001). The biochemical parameters at the onset were similar. On comparing microhematuria, hypertension, and renal insufficiency at presentation, we observed that two or more of these features were present in all patients with MPGN and only in 19.6% of adolescents with MCD, mesangioproliferative glomerulonephritis, and FSGS. The frequency of steroid resistance was significantly higher in group B (P<0.001). In conclusion, adolescent-onset NS differs from the childhood variety in having a significantly higher frequency of hematuria, steroid resistance, and evidence of non-MCD, especially MPGN, on histopathology. Kidney biopsy can be restricted to those adolescents who have at least two abnormal clinical/biochemical features or are steroid non-responders.

Adolescent↗
PubMed2001

Prognostic significance of distal renal tubular acidosis in posterior urethral valve.

The prognostic significance of distal renal tubular acidosis (DRTA) in the development of overt nephropathy (ON) in children with posterior urethral valves (PUV) is not clear. This condition was studied prospectively in 22 children with posterior urethral valve (PUV), with normal renal function. Prior to surgery, the children with ON had a higher incidence of bilateral reflux (P=0.006), but the difference was not significant for age at surgery (P=0.31), duration of voiding symptoms prior to surgery (P=0.30), presence of DRTA (P=0.35) and bladder abnormalities (P=0.27), with none of these factors being significant on logistic regression analysis. At the end of the follow-up, after surgery, age at surgery (P < or = 0.0001), duration of voiding symptoms prior to surgery (P < or = 0.0003), persistent DRTA (P=0.0001) and persistent bladder dysfunction (P=0.02) after surgery were significantly higher in children with ON. On univariate logistic regression analysis, age at surgery (P=0.009), duration of voiding symptoms prior to surgery (P=0.01), persistent DRTA (P=0.002) and persistent bladder abnormalities (P=0.03) after surgery were significant for ON after surgery, but on stepwise multivariate logistic regression analysis only persistent DRTA (P=0.002) turned out to be significant. We conclude that persistent DRTA after surgery can predict overt nephropathy in children with PUV after surgery.

Acidosis, Renal Tubular↗
PubMed2001

Treatment of childhood headaches.

Migraine and tension-type headaches are two of the most common types of primary headache disorders in children. Migraine is a primary central nervous system disorder characterized by triggered or spontaneous episodes of activation of trigemino-vascular complex, neurogenic inflammation around vessels and meninges, and stimulation of the peripheral and central pain pathways of the trigemino-cervical complex. The triptans, by their selective agonistic action on 5-HT1B/1D receptors, are very effective in the treatment of migraine pain and associated symptoms. Early studies on the safety and efficacy of triptans in the management of childhood migraine show encouraging results. We propose a stratified-care model for the management of migraine in children, and discuss pharmacotherapy based on the pathophysiologic mechanisms of migraine pain. Management of tension-type headaches requires comprehensive medical and psychologic evaluation and an individualized approach for a successful outcome.

Acute Disease↗
PubMed2001

Curvularia lunata endophthalmitis with secondary keratitis.

PURPOSE: To report a case of pseudophakic endophthalmitis with secondary keratitis caused by Curvularia lunata. METHODS: A 40-year-old man presented with a fluffy mass in the anterior chamber with low-grade delayed postoperative inflammation in the right eye. RESULTS: The anterior chamber and vitreous aspirate demonstrated C. lunata. A large corneal infiltrate developed after aspiration of the mass. Treatment with systemic, topical, and intraocular antifungal agents cleared the vitreous, but the cornea perforated. CONCLUSION: Delayed low-grade infection with a fluffy mass in the anterior chamber after cataract surgery can rarely be a clinical presentation of dematiaceous fungal infection. Secondary keratitis may result after a diagnostic aspiration.

Adult↗
PubMed2001

Fungal endophthalmitis following cataract surgery: clinical presentation, microbiological spectrum, and outcome.

PURPOSE: To determine the clinical presentation, microbiological spectrum, and outcome in cases of fungal endophthalmitis following cataract surgery. DESIGN: Observational case series. METHODS SETTING: Tertiary referral hospital. PATIENTS: Retrospective analysis of 27 cases of smear- and culture-proven fungal endophthalmitis. INTERVENTION: Pars plana vitrectomy in 18 eyes, where the corneal condition did not preclude the same. All eyes received intravitreal amphotericin B and dexamethasone along with systemic antifungal agents. MAIN OUTCOME MEASURES: Functional success: Final visual acuity of 3/60 or better with attached retina. Anatomical success: Final visual acuity of better than light perception with preserved anatomy of globe. RESULTS: The majority of the eyes (22 of the 27) had early onset and diffuse presentation (that is, anterior segment as well as posterior vitreous exudates). Substantial corneal involvement was seen in 14 eyes (51.85%). Aspergillus sp. was the most common isolate. Multivariate analysis using forward stepwise logistic regression showed corneal involvement as the single most important risk factor in determining final visual outcome (P =.0429). CONCLUSIONS: Early onset and diffuse presentation, which mimics bacterial endophthalmitis, stresses the importance of both bacterial and fungal cultures from intraocular fluids to reach a diagnosis apart from the clinical judgment. Corneal involvement was the most important predictor of outcome in cases of fungal endophthalmitis.

Adult↗
PubMed2001

Analyses of myo-electrical silence of erectors spinae.

Electromyographic activity of the erector spinae was studied in 25 healthy, young individuals during forward bending and then coming back to erect posture. Sudden onset of electrical silence called the flexion-relaxation phenomenon was seen to occur in all at 57% of the maximum hip flexion and at 84% of the maximum vertebral flexion. Abrupt re-commencement of the activity was seen at almost similar flexion angle while coming back to erect position. The experiment was repeated with the buttocks held against the wall so as to prevent the posterior migration of the pelvis and also the hip flexion to some extent. The effect was to produce inhibition of the electrical activity earlier at 75% of maximum vertebral flexion (p<0.001) while reactivation of erector spinae occurred soon after the extension started from the maximum trunk flexion. Eleven male subjects repeated the experimental task holding 22 lb weight in front and then on their back tied around the iliac crest. In both the instances the myo-electrical silence was found to occur at greater vertebral flexion. It is concluded that the passive equilibrium between gravity induced tensile torque and the extension torque of stretched posterior vertebral ligaments is responsible for the flexion-relaxation phenomenon than the stretch receptors.

Adult↗
PubMed2001

Novel AMPA receptor potentiators LY392098 and LY404187: effects on recombinant human AMPA receptors in vitro.

The present study describes the activity of two novel potent and selective AMPA receptor potentiator molecules LY392098 and LY404187. LY392098 and LY404187 enhance glutamate (100 microM) stimulated ion influx through recombinant homomeric human AMPA receptor ion channels, GluR1-4, with estimated EC(50) values of 1.77 microM (GluR1(i)), 0.22 microM (GluR2(i)), 0.56 microM (GluR2(o)), 1.89 microM (GluR3(i)) and 0.20 microM (GluR4(i)) for LY392098 and EC(50) values of 5.65 microM (GluR1(i)), 0.15 microM (GluR2(i)), 1.44 microM (GluR2(o)), 1.66 microM (GluR3(i)) and 0.21 microM (GluR4(i)) for LY404187. Neither compound affected ion influx in untransfected HEK293 cells or GluR transfected cells in the absence of glutamate. Both compounds were selective for activity at AMPA receptors, with no activity at human recombinant kainate receptors. Electrophysiological recordings demonstrated that glutamate (1 mM)-evoked inward currents in human GluR4 transfected HEK293 cells were potentiated by LY392098 and LY404187 at low concentrations (3-10 nM). In addition, both compounds removed glutamate-dependent desensitization of recombinant GluR4 AMPA receptors. These studies demonstrate that LY392098 and LY404187 allosterically potentiate responses mediated by human AMPA receptor ion channels expressed in HEK 293 cells in vitro.

Allosteric Regulation↗
PubMed2001

Analgesic efficacy of ketorolac and morphine in neonatal rats.

Ketorolac is a potent nonsteroidal antiinflammatory drug (NSAID). In adult humans and animals, its analgesic efficacy can be comparable to opiates. However, it has not been studied in neonatal animals. We conducted a blinded, controlled study comparing the effects of ketorolac and morphine in neonatal rats using the formalin model. Animals were given intraperitoneal (i.p.) injections of ketorolac or morphine at 3 or 21 days of age. Ketorolac had an analgesic and antiinflammatory effect in 21-day-old pups, but not in the 3-day-olds. Morphine had a significant analgesic, but no antiinflammatory effect at both ages. These results indicate that ketorolac is an effective analgesic agent in preweaning, but not neonatal rats. Opiates may be more appropriate analgesics in neonates.

Age Factors↗
PubMed2001

Effect of in-the-bag intraocular lens fixation on the prevention of posterior capsule opacification.

PURPOSE: To compare the incidence of posterior capsule opacification (PCO) after extracapsular cataract extraction (ECCE) and phacoemulsification and to evaluate the role of posterior chamber intraocular lens (PC IOL) haptic fixation and biomaterial/design in reducing the incidence. SETTING: Postgraduate Institute of Medical Education and Research, Chandigarh, India; Center for Research on Ocular Therapeutics and Biodevices, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: This study comprised 278 eyes of 263 patients having ECCE and 318 eyes of 297 patients having phacoemulsification with PC IOL implantation. Posterior capsule opacification leading to a decrease in Snellen visual acuity of 2 or more lines was considered visually significant. The presence of PCO and IOL haptic fixation were evaluated postoperatively using slitlamp biomicroscopy. Haptic position was noted as in-the-bag (B-B), 1 haptic in the bag and 1 in the sulcus (bag-sulcus [B-S]), or both haptics out of the bag (sulcus-sulcus [S-S]). In addition, the rate of visually significant PCO was compared among 3 IOL biomaterials: poly(methyl methacrylate), silicone, and hydrophobic acrylic. RESULTS: Visually significant PCO occurred in 42.45% of eyes having ECCE and 19.18% of eyes having phacoemulsification (P <.001, chi-square test) after a mean follow-up of 2.4 years +/- 0.7 (SD). In both groups, visually significant PCO was significantly less in eyes with B-B fixation than in those with B-S or S-S fixation (P <.001). The rate of visually significant PCO in all eyes in the phacoemulsification group with B-B fixation was low (11.90%) and was significantly lower in eyes with a hydrophobic acrylic IOL (2.22%; P <.05, chi-square test). CONCLUSIONS: In-the-bag PC IOL fixation is required to consistently reduce the incidence of PCO. Thorough removal of lens substance, including hydrodissection-assisted cortical cleanup, and in-the-bag PC IOL fixation seem to be the most important factors in reducing PCO, regardless of surgical procedure or IOL type used. Intraocular lens biomaterial and design also help prevent PCO.

Biocompatible Materials↗