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M Srinivas

Publications and source records attributed to M Srinivas.

At least 19 recordsLinked to original sources
PubMed2002

Evidence for a role of the N-terminal domain in subcellular localization of the neuronal connexin36 (Cx36).

The expression and functional properties of connexin36 (Cx36) have been investigated in two neuroblastoma cell lines (Neuro2A, RT4-AC) and primary hippocampal neurons transfected with a Cx36-enhanced green fluorescent protein (EGFP) expression vector. Transfected cells express Cx36-EGFP mRNA, and Cx36-EGFP protein is localized in the perinuclear area and cell membrane. Upon differentiation of cell lines, Cx36-EGFP protein was detectable in processes with both axonal and dendritic characteristics. Small gap junction plaques were found between adjacent cells, and electrophysiological recordings demonstrated that the electrical properties of these gap junctions were virtually indistinguishable from those reported for native Cx36. Mutagenesis of Cx36 led to the identification of a structural element that interferes with normal protein localization. In contrast, site directed mutagenesis of putative protein phosphorylation motifs did not alter subcellular localization. This excludes phosphorylation/dephosphorylation as a major regulatory step in Cx36 protein transport.

Animals↗
PubMed2002

Potential of MRI and 31P MRS in the evaluation of experimental testicular trauma.

OBJECTIVES: To prognosticate and assess the metabolic status of germ cells of the testis after unilateral blunt testicular trauma using both magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS). MRI is a noninvasive technique suitable for evaluating testicular trauma, and MRS is useful in assessing the metabolic status of the testis. METHODS: The right testis of 35 male prepubertal Wistar rats, aged 30 days, was explored through an inguinal incision. The rats were randomized into control (group 1, sham surgery, n = 10) and study (n = 25) groups. The study group received unilateral blunt testicular trauma to the right testis. T(1)- and T(2)-weighted proton MRI of the ipsilateral testis were taken 6 hours after sham surgery or injury, and the rats were stratified on the basis of the absence or presence of intratesticular hemorrhage on MRI into groups 2 (n = 14) and 3 (n = 11), respectively. At 60 days of age, the contralateral testis of each rat was evaluated by 31P MRS and histologic examination. Quantification of phosphomonoesters, phosphodiesters, phosphocreatine, and adenosine triphosphate (gamma, alpha, and beta) was done. RESULTS: A statistically significant difference (P <0.05) in the phosphomonoester/adenosine triphosphate ratio, seminiferous tubular diameter, and Johnsen score of the contralateral testis was observed, indicating decreased testicular maturation of the contralateral testis in group 3 rats compared with groups 1 and 2. CONCLUSIONS: MRI after testicular trauma helped to stratify the extent of injury as determined by the presence or absence of intratesticular hemorrhage with prognostic value; 31P MRS and histologic examination revealed that testicular trauma significantly affects the maturation of the contralateral testis.

Age Factors↗
PubMed2002

Moderate visual impairment in India: the Andhra Pradesh Eye Disease Study.

AIM: To assess the prevalence and demographic associations of moderate visual impairment in the population of the southern Indian state of Andhra Pradesh. METHODS: From 94 clusters in one urban and three rural areas of Andhra Pradesh, 11 786 people of all ages were sampled using a stratified, random, cluster, systematic sampling strategy. The eligible people were invited for interview and detailed dilated eye examination by trained professionals. Moderate visual impairment was defined as presenting distance visual acuity less than 6/18 to 6/60 or equivalent visual field loss in the better eye. RESULTS: Of those sampled, 10,293 (87.3%) people participated in the study. In addition to the previously reported 1.84% prevalence of blindness (presenting distance visual acuity less than 6/60 or central visual field less than 20 degrees in the better eye) in this sample, 1237 people had moderate visual impairment, an adjusted prevalence of 8.09% (95% CI 6.89 to 9.30%). The majority of this moderate visual impairment was caused by refractive error (45.8%) and cataract (39.9%). Increasing age, female sex, decreasing socioeconomic status, and rural area of residence had significantly higher odds of being associated with moderate visual impairment. CONCLUSIONS: These data suggest that there is a significant burden of moderate visual impairment in this population in addition to blindness. Extrapolation of these data to the population of India suggests that there were 82 million people with moderate visual impairment in the year 2000, and this number is likely to be 139 million by the year 2020 if the current trend continues. This impending large burden of moderate visual impairment, the majority of which is due to the relatively easily treatable refractive error and cataract, would have to be taken into account while estimating the eye care needs in India, in addition to dealing with blindness. Specific strategies targeting the elderly population, people with low socioeconomic status, those living in the rural areas, and females would have to be implemented in the long term to reduce moderate visual impairment.

Adolescent↗
PubMed2001

Quinine blocks specific gap junction channel subtypes.

We demonstrate that the antimalarial drug quinine specifically reduces currents through gap junctions formed by some connexins (Cx) in transfected mammalian cells, but does not affect other gap junction types. Quinine blocked Cx36 and Cx50 junctional currents in a reversible and concentration-dependent manner with half maximal blocking concentrations of 32 and 73 microM, respectively; Hill coefficients for block by quinine were about 2 for both connexins. In contrast, quinine did not substantially block gap junction channels formed by Cx26, Cx32, Cx40, and Cx43, and only moderately affected Cx45 junctions. To determine the location of the binding site of quinine (pKa = 8.7), we investigated the effect of quinine at various external and internal pH values and the effect of a permanently charged quaternary derivative of quinine. Our results indicate that the binding site for quinine is intracellular, possibly within the pore. Single-channel studies indicated that exposure to quinine induced slow transitions between open and fully closed states that decreased open probability of the channel. Quinine thus offers a potentially useful method to block certain types of gap junction channels, including those between neurons that are formed by Cx36. Moreover, quinine derivatives that are excluded from other types of membrane channels may provide molecules with connexin-specific as well as connexin-selective blocking activity.

Antimalarials↗
PubMed2001

Calmodulin kinase pathway mediates the K+-induced increase in Gap junctional communication between mouse spinal cord astrocytes.

Astrocytes are coupled to one another by gap junction channels that allow the diffusion of ions and small molecules throughout the interconnected syncytium. In astrocytes, gap junctions are believed to participate in spatial buffering removing the focal excess of potassium resultant from intense neuronal activity by current loops through the syncytium and are also implicated in the propagation of astrocytic calcium waves, a form of extraneuronal signaling. Gap junctions can be modulated by several factors, including elevation of extracellular potassium concentration. Because K(+) elevation is a component of spinal cord injury, we evaluated the extent to which cultured spinal cord astrocytes is affected by K(+) levels and obtained evidence suggesting that a Ca(2+)-calmodulin (CaM) protein kinase is involved in the K(+)-induced increased coupling. Exposure of astrocytes to high K(+) solutions induced a dose-dependent increase in dye coupling; such increased coupling was greatly attenuated by reducing extracellular Ca(2+) concentration, prevented by nifedipine, and potentiated by Bay-K-8644. These results indicate that K(+)-induced increased coupling is mediated by a signaling pathway that is dependent on the influx of Ca(2+) through L-type Ca(2+) channels. Evidence supporting the participation of the CaM kinase pathway on K(+)-induced increased coupling was obtained in experiments showing that calmidazolium and KN-93 totally prevented the increase in dye and electrical coupling induced by high K(+) solutions. Because no changes in connexin43 expression levels or distribution were observed in astrocytes exposed to high K(+) solutions, we propose that the increased junctional communication is related to an increased number of active channels within gap junction plaques.

Animals↗
PubMed2001

Betamethasone in plus phenobarbitone prior to hepatobiliary scintigraphy increases diagnostic accuracy in infants with jaundice.

OBJECTIVE: In the diagnostic work up of the child with neonatal obstructive cholangiopathy (NOC), hepatobiliary scintigraphy (HBS) determines the need for peroperative cholangiography (POC). Traditionally, phenobarbitone is recommended to prime the liver to HBS. This retrospective study was designed to evaluate whether addition of the betamethasone (BM) alters the diagnostic accuracy of the HBS in distinguishing neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA). METHODS: Between 1993-1999, 202 patients presented with NOC and this study was not designed as a prospective randomized clinical trial. Of these, 126 patients had received Phenobarbitone (Group I) and the remaining 76 (Group II) had received BM in addition to the PB in a dose of 5 mg/k/d and 2.2 mg/k/d respectively for 7 days prior to HBS. RESULTS: Retrospective analysis revealed that, in the Group I, 41 showed excretion and 85 did not show any excretion of the radiopharmaceutical and the latter underwent POC which revealed that 31 patients (36%) of them showed patent biliary tract. In group II, 32 patients revealed excretion and 44 did not show any excretion of the radiopharmaceutical and the latter had undergone POC, which revealed that only 8 patients (18%) showed patent biliary tract. The percentages of false positives (36% vs 18%) was statistically significant (p < 0.03). CONCLUSION: Addition of BM increases the diagnostic accuracy of the HBS and this would lead to decreased need for POC to distinguish NH from EHBA.

Betamethasone↗
PubMed2001

Leucocytoclastic vasculitis in infant.

Acute hemorrhagic edema of infancy is a laucocytoclastic vasculitis characterized by a triad of fever, large purpuric skin lesions and edema. The presentation is often dramatic. The manifestations are often misinterpreted as a septicemic illness. We report the occurrence of this syndrome in a 1 1/2-year-old-child, highlighting some of the diagnostic and therapeutic problems encountered.

Humans↗
PubMed2001

Association between lower hair zinc levels and neural tube defects.

Though folic acid supplementation has reduced the incidence of Neural Tube Defects (NTD), NTD still constitutes one of the important congenital malformations having wide medical, social and ethical implications. Zinc deficiency has been reported to produce NTD in animals. This study was designed to evaluate zinc status of the newborn babies with NTD and their mothers. Eighty newborn babies with NTD and their mothers served as cases. Eighty apparently normal newborn babies and their mothers served as controls. Serum and scalp hair zinc levels were analyzed by atomic absorption spectrophotometry. The mean (+/- SD) serum and hair levels in normal mothers were 74.1 +/- 4.1 micrograms/dl and 142.3 +/- 8.0 micrograms/g respectively. The mean (+/- SD) serum and hair levels of the mothers who delivered NTD babies were 75.7 +/- 5.6 micrograms/dl and 129.9 +/- 5.3 micrograms/g respectively. The mean (+/- SD) serum and hair levels in normal newborn babies were 77.8 +/- 5.3 micrograms/dl and 188.8 +/- 6.2 micrograms/g respectively. The mean (+/- SD) serum and hair levels in NTD babies were 80.1 +/- 12.9 micrograms/dl and 174.2 +/- 10.7 micrograms/g respectively. The hair zinc levels of the affected babies and their mothers were significantly lower (P < 0.001) than the controls. This study has found association between NTD and decreased hair zinc levels and large population based studies are recommended to confirm the association between zinc and NTD and to investigate whether zinc supplementation would reduce the overall incidence of NTD.

Developing Countries↗
PubMed2001

AIIMS clinical score: a reliable aid to distinguish neonatal hepatitis from extra hepatic biliary atresia.

It is important to distinguish neonatal hepatitis (NH) from extra hepatic biliary atresia (EHBA) in a neonate presented with jaundice as the former is purely medical management and the latter requires surgical procedure at the earliest. The observations on the critical evaluation of the neonatal jaundice cases led us to propose AIIMS clinical score (ACS) and this retrospective study was designed to evaluate the reliability of the ACS in all the 120 babies with jaundice referred to the pediatric surgery department during the past 10 year period. The ACS described here is based on 5 clinical parameters--Age, Jaundice, Colour of urine and stool and Clinical examination of liver. The accuracy of the hepatobiliary scan (HBS) with respect to the diagnosis of EHBA in this series, as compared to per operative cholangiography (POC) which is considered as the gold standard to distinguish these conditions was only 68%. However, ACS showed a sensitivity of 91.5%, a specificity of 76.3%, positive predictive value of 89.2%, negative predictive value of 80.5% and an overall diagnostic accuracy of 86.6%. ACS is reliable to distinguish NH from EHBA at bedside.

Biliary Atresia↗
PubMed2001

Azygos vein anomaly: the best predictor of a long gap in esophageal atresia and tracheoesophageal fistula.

The gap between the pouches has a direct bearing on the tension at the anastomosis that ultimately determines the anastomotic leak in esophageal atresia with or without tracheoesophageal fistula (EA-TEF). Long-gap EA has been reported to be associated with aortic-arch anomalies and 13 pairs of ribs. Our observation that EA-TEF with an azygos-vein anomaly (AVA) invariably had a long gap led us to retrospectively analyze our data. The mean gaps (+/- SD) in the groups with 13 pairs of ribs (n = 6), right-sided aortic arch (n = 16), and AVA (n = 9) were 1.25 +/- 0.27, 2.18 +/- 0.98, and 3.16 +/- 0.16 cm, respectively. There was no statistically significant difference in the gap in patients who had 13 pairs of ribs compared with controls who had 12 pairs of ribs. The gap was highest in the AVA group and was statistically significant (P < 0.001) compared with patients with a normal azygos vein. In addition, the AVA group had a significant increase in mortality (P < 0.05) compared to the groups with a normal azygos vein; although there was no statistically significant difference in other factors: birth weight, time between delivery and surgery, cardiac anomalies, anorectal malformations, renal malformations, and chest infection in the AVA group and controls. An extra pair of ribs is not associated with a long gap, and an AVA per se is an independent predictor of a long gap and mortality in EA-TEF.

Abnormalities, Multiple↗
PubMed2001

Telemedicine in pediatric surgery.

Telemedicine is a new academic specialty at the crossroads of medical informatics whose potential is still largely untapped by pediatric surgeons. Telemedicine aims to alleviate travel concerns associated with the delivery of health care, to bring expert pediatric surgeons to areas where currently none exist, and to improve coordination between pediatric surgeons, transcending all barriers. Today, it is possible to transmit all digitized data--roentgenograms, echocardiograms, radiologic images, intraoperative photographs, histologic images, etc., and to consult specific experts in the subspecialties of childcare. It is possible to train and guide surgical trainees by experts without their physical presence. In the future, telemedicine will constitute an integral part of the health care of children and the training of pediatric surgeons.

Child↗
PubMed2001

Evaluation of developing rat testis by phosporus 31P magnetic resonance spectroscopy and DNA flowcytometry.

For the assessment of germ-cell maturation of the seminiferous tubules, DNA flowcytometry is a rapid and sensitive method. Phosporus 31P magnetic resonance spectroscopy (MRS) is a non-invasive alternative that demonstrates the metabolic status of the testis, reflecting the type and relative proportion of germ cells in the testis. This study was designed to evaluate the utility of 31P MRS in reflecting the haploid-cell population of the testis as measured by DNA flowcytometry. A single testicle was evaluated in male Wistar pre-pubertal rats at 30, 40, 50, and 60 days of age. In order to minimize the contamination of signals from the contralateral testis, scrotum, and tail, the technique was modified and the testis was evaluated ex-vivo with an intact blood supply. At 30 days of age the percentage of haploid cells was 43.6 +/- 1.8, and this increased to 72.7 +/- 1.4 at 60 days of age. During this period, the testicular phosphomonoester/adenosine triphosphate (PM/ATP) ratio changed from 1.70 +/- 0.21 to 0.32 +/- 0.08. There was a significant (P < 0.001) linear correlation between the proportion of haploid cells evaluated by DNA flowcytometry and the PM/ATP ratio evaluated by 31P MRS. 31P MRS is thus a reliable, noninvasive technique for accurately assessing the status of the seminiferous epithelium.

Animals↗
PubMed2001

Functional outcome after pyeloplasty for unilateral symptomatic hydronephrosis.

The functional outcome and factors influencing improvement after pyeloplasty for ureteropelvic junction (UPJ) obstruction are still debated. This retrospective study was aimed at evaluating the factors associated with functional improvement in symptomatic unilateral hydronephrosis (HDN). Patients (n = 68) who underwent successful pyeloplasty for unilateral symptomatic UPJ obstruction without any other associated urological abnormality were included. Preoperative evaluation included a diuretic renogram (DR) to confirm obstruction and assess the split renal function (SRF). A follow-up DR was obtained 3 months and 1, 2, and 5 years postoperatively. An absolute increase in the differential function of the operated kidney by over 5% was considered significant; such kidneys were classified as improved (group A) and the others as unimproved (group B). The difference between the preoperative and 3-month SRF was highly significant (P < 0.001). Significant (P < 0.01) improvement in SRF continued until 1 year after pyeloplasty. Patients who presented with a mass had significantly greater improvement (P < 0.05) than those who presented with other clinical features. In group A, a significantly higher number of patients presented with a mass. It was also evident that patients aged less than 1 year showed significantly greater (P < 0.01) improvement in SRF than older patients. Thus, in unilateral symptomatic HDN with impaired function, patients who present with a mass or those in whom pyeloplasty was performed before 1 year of age showed significantly greater improvement.

Child↗
PubMed2001

Percutaneous nephrostomy in children with ureteropelvic junction obstruction and poor renal function.

OBJECTIVES: To evaluate the results of performing percutaneous nephrostomy (PCN) in all patients with kidneys with ureteropelvic junction obstruction (UPJO) and split renal function (SRF) of less than 10%, because the management of such cases is still under debate. If SRF improves, we perform pyeloplasty, otherwise nephrectomy is done. METHODS: The records of all patients with UPJO (n = 20; 17 unilateral and 3 solitary kidney) with poor function who underwent PCN were analyzed. The PCN remained in situ for at least 4 weeks, during which patients received low-dose oral trimethoprim prophylaxis. Repeated renography was obtained after 4 weeks. If no improvement in the SRF had occurred, nephrectomy was performed, otherwise pyeloplasty was performed. The patients were followed up with renograms at 3 months, 1 year, 2 years, and 5 years. RESULTS: Twelve of 17 kidneys with unilateral UPJO improved after PCN drainage and underwent pyeloplasty. The 5 kidneys that did not show improvement in the SRF underwent nephrectomy. In the patients with unilateral UPJO who improved after PCN drainage, the SRF increased to 29.2% +/- 12.6% and pyeloplasty was performed. At a mean follow-up of 2.3 years, none of these patients had developed hypertension, and the most recent SRF value was 31.4% +/- 12.8%. CONCLUSIONS: Most of the poorly functioning UPJO kidneys show improvement in function and not all such kidneys should be removed without a trial of PCN.

Child↗
PubMed2001

A thyroid hormone receptor that is required for the development of green cone photoreceptors.

Color vision is facilitated by distinct populations of cone photoreceptors in the retina. In rodents, cones expressing different opsin photopigments are sensitive to middle (M, 'green') and short (S, 'blue') wavelengths, and are differentially distributed across the retina. The mechanisms that control which opsin is expressed in a particular cone are poorly understood, but previous in vitro studies implicated thyroid hormone in cone differentiation. Thyroid hormone receptor beta 2 (TR beta 2) is a ligand-activated transcription factor that is expressed in the outer nuclear layer of the embryonic retina. Here we delete Thrb (encoding Tr beta 2) in mice, causing the selective loss of M-cones and a concomitant increase in S-opsin immunoreactive cones. Moreover, the gradient of cone distribution is disturbed, with S-cones becoming widespread across the retina. The results indicate that cone photoreceptors throughout the retina have the potential to follow a default S-cone pathway and reveal an essential role for Tr beta 2 in the commitment to an M-cone identity. Our findings raise the possibility that Thrb mutations may be associated with human cone disorders.

Animals↗
PubMed2001

Ergonomic problems associated with laparoscopy.

PURPOSE: Failure to understand the ergonomics of laparoscopic surgery has a potential to pose health problems for the surgeons. This study was planned to assess the prevalence, significance, and awareness of ergonomic problems associated with laparoscopy. MATERIAL AND METHODS: A questionnaire designed to assess the frequency and degree of physical discomfort practicing surgeons experienced and their awareness of the responsible factors was distributed to approximately 350 attendees of the Live International Workshop and CME on Laparoscopic Urologic Surgery. The response sheets were analyzed. RESULTS: Two hundred four attendees completed the questionnaire, of whom 131 were performing laparoscopic surgery (Group A). The rest (N = 73) were practicing only conventional surgery (Group B). The correct answer to the pictorial question, which tested the correct grip technique, was 81% and 56% in Group A and B, respectively (P = 0.0003). Group A surgeons were significantly (P = 0.04) better at answering the questions on neurapraxia. There was a statistically significant (P = 0.004) increase in the frequency of finger numbness and eye strain in Group A surgeons compared with Group B. Within Group A, finger numbness (P = 0.03) and eye strain (P = 0.002) were significantly greater in the junior laparoscopic surgeons than in senior laparoscopic surgeons. Surgeons having <2 years of laparoscopic surgical experience were significantly more affected. CONCLUSIONS: Surgeons performing laparoscopy have significant ergonomic problems, especially finger numbness and eye strain. Junior laparoscopic surgeons and surgeons with <2 years of laparoscopic surgical experience are more affected.

Adult↗
PubMed2001

Growth-suppressive function of human connexin32 in a conditional immortalized mouse hepatocyte cell line.

Mouse hepatocytes immortalized with a temperature-sensitive allele of the SV40 large T-antigen (CHST8 cells) were found to lack the high expression of the gap junction proteins Cx26 and Cx32 that characterizes normal mouse hepatocytes, expressing instead Cx43 and Cx45 at minimal levels. In order to examine the growth suppressive function of Cx32 on hepatocytes, we transfected these CHST8 cells with human Cx32 complementary deoxyribonucleic acid and measured the growth rates at 33, 37, and 39 degrees C. Expression of human Cx32 and its messenger ribonucleic acid in the stable cell lines was confirmed by immunocytochemistry and by Western and Northern blots analyses. Dye transfer following lucifer yellow injection into the transfectants was extensive; Cx32 channels displayed unitary conductances of about 70 pS and were moderately voltage sensitive. When cultured at 33 and 39 degrees C, growth rates of both parental cells and transfectants were of the same level. When examined at 37 degrees C, growth rate of the transfectant, which highly expressed Cx32 at the membranes, was significantly decreased compared to the parental cells. However, no changes in the expression of Cx32 protein in the transfectants were observed between 33 and 37 degrees C. These results suggest that Cx32 expression could inhibit hepatocyte growth in vitro using the conditional immortalized cells. Cx32 transfectants using a conditional immortalized mouse hepatocyte may be useful for examining the mechanisms of growth and differentiation in hepatocytes by gap junction expression.

Animals↗