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Biomedical subjects

M Srinivasan

Publications and source records attributed to M Srinivasan.

At least 55 records · Page 3Linked to original sources
PubMed2001

An outbreak of trematode-induced granulomas of the conjunctiva.

PURPOSE: To describe the epidemiologic, clinical, and histopathologic features of trematode granulomas of the conjunctiva, eyelid, and anterior chamber in pediatric patients. DESIGN: Prospective noncomparative case series. PARTICIPANTS: Forty-one children from a southern Indian village with conjunctival granulomas. METHODS: The village of Sellananthal was selected for a field visit after analysis of earlier hospital-based allergic conjunctival granuloma cases. Children with ocular diseases were examined, and histories of exposure to assumed risk factors and clinical findings were evaluated. Selected patients were brought to the base hospital for excisional biopsy. Serial sections obtained from the excised nodules were examined for the presence of a parasite. MAIN OUTCOME MEASURES: Histopathologic examination of excised conjunctival lesions or response of lesions to local medical therapy. RESULTS: In this year-long prospective study, 41 children (16 years or younger; 38 boys and 3 girls) with clinical features of allergic conjunctival granulomas were examined. Thirty-four patients were from a single village located in the southern Indian state of Tamil Nadu; the remaining 7 were from various parts of the same state. All children swam in their village's freshwater pond. Twenty patients with nodules less than 5 mm in diameter received medical treatment; 13 with larger nodules underwent surgical excision of the lesions. Nine of these 13 cases revealed a zonal granulomatous inflammation admixed with eosinophilic leukocytes; 4 of these 9 displayed fragments of the tegument and internal structures of a trematode and Splendore-Hoeppli phenomenon. The remaining 4 of the 13 cases revealed nongranulomatous inflammation made up of lymphocytes, histiocytes, and eosinophils. Eight patients refused surgical treatment. CONCLUSIONS: In southern India, one cause of allergic conjunctival granulomas in children seems to be trematode infection. The clustering of cases in a single village and exposure to a village freshwater pond indicate the need for an epidemiologic investigation and study of the parasite's life cycle. Sporadic cases from other parts of the state with similar histories of exposure to their local pond or river water suggest a widespread distribution of the etiologic agent.

Adolescent↗
PubMed2001

Molecular adaptations in islets from neonatal rats reared artificially on a high carbohydrate milk formula.

Four day-old rat pups artificially raised on a high carbohydrate (HC) milk formula during their suckling period immediately develop hyperinsulinemia which persists into adulthood despite weaning onto lab chow on day 24. The present study investigates the molecular adaptations in islets isolated from neonatal rats in response to this dietary treatment during their suckling period. There is a significant increase in the level of preproinsulin mRNA and insulin biosynthesis in 12 day-old HC islets compared to islets from age-matched mother-fed (MF) control rats. Pancreatic duodenal homeobox factor-1 (PDX-1) modulates pancreatic ontogeny as well as preproinsulin gene expression in islets from neonatal rats. The mRNA level, DNA binding activity and protein content of PDX-1 are significantly increased in HC islets. The stress-activated protein kinase-2 and phosphatidylinositol 3-kinase have been reported to modulate PDX-1 activity in islets. The mRNA levels of these kinases are increased in HC islets. The mRNA level of upstream stimulatory factor (a modulator of PDX-1 gene expression) is also significantly increased in HC islets. These results indicate that the upregulation of several molecular events, including increases in the gene expression of preproinsulin, transcription factors and kinases may contribute to the chronic hyperinsulinemic state in the HC rats.

Journal Article↗
PubMed2001

Quantitative estimation of PCNA, c-myc, EGFR and TGF-alpha in oral submucous fibrosis--an immunohistochemical study.

The objectives of the present study were to evaluate the expression of three proliferation markers, viz., epidermal growth factor receptor (EGFR), transforming growth factor-alpha (TGF-alpha) and proliferating cell nuclear antigen (PCNA) and one genomic marker, c-myc in OSMF. Oral tissues were stained with monoclonal antibodies to PCNA, c-myc, TGF-alpha and EGFR. The results were analyzed with Photoquant image analysis software. The expression of PCNA, c-myc, TGF-alpha and EGFR was higher in oral submucous fibrosis (OSMF) than in normal control oral mucosa. The oral epithelium was divided into a proliferative compartment (stratum germinativum) and a differentiated compartment (stratum spinosum). A differential pattern of expression of PCNA and c-myc was observed in OSMF. While the intensity of staining decreased, the percent area of expression of PCNA and c-myc increased in stratum germinativum in OSMF (P<0.05). This suggests that greater proportions of cells exhibit PCNA and c-myc immunoreactivity and are in the proliferative pool in OSMF. TGF-alpha levels increased in the proliferative layers and EGFR levels increased in the differentiated layers (P<0.05) of the oral epithelium in OSMF. Quantitative measurement of these oncoproteins substantiates the precancerous nature of OSMF and may provide intermediate end-points in prospective chemopreventive trials.

Adult↗
PubMed2001

Evaluating psychological debriefing: are we measuring the right outcomes?

The efficacy of critical incident stress debriefing (CISD) and psychological debriefing (PD) following potentially traumatising events has recently been challenged after a number of recent randomised controlled trials (RCTs) failed to demonstrate that CISD or PD prevents or reduces the incidence of posttraumatic stress disorder (PTSD). These studies have used measures of PTSD as the principal outcome and have generally not measured comorbid psychopathology, behavioral or social dysfunction. In a recent RCT of group debriefing amongst British soldiers returning from peacekeeping operations in Bosnia, PD had a significant effect in reducing a worrying level of alcohol misuse in the sample. The findings of this study suggest that that it is premature to conclude that debriefing is ineffective and that a broader range of outcome measures should be employed in future trials of debriefing.

Adult↗
PubMed2001

Mitochondrial-encoded gene regulation in rat pancreatic islets.

Mitochondrial adenosine triphosphate (ATP) generation plays a major role in insulin secretion in pancreatic islet beta cells. The relationship between age and nutritional status of the islet and mitochondrial gene messenger RNA (mRNA) expression was investigated. Three animal groups were studied: infant (12-day-old) rats fed either mother's milk or a high carbohydrate (HC) diet; young (2 to 4-month-old) rats; and old (12 to 14-month-old) rats. The expression of mitochondrial cytochrome oxidase (CYO) (subunits I, II, and III), beta-nicotinamide adenine dinucleotide, reduced form dehydrogenase subunit 4 (NADH-DH4), and ATP synthase (subunit 6) (ATP-SYN6) mRNAs was characterized by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR). The mitochondrial gene mRNAs were identified in each of the groups of rat islets and in RINm5F cells. CYO-II mRNA expression in young and old rat pancreatic islets was 12.7- and 8.2-fold higher, respectively, compared with the level in infant rat islets. The expression of NADH-DH4 and ATP-SYN6 mRNAs was 47% and 40% lower, respectively, in young rat islets compared with the level in infant rat islets. CYO-I, CYO-III, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase (GPDH) mRNA expression did not differ between experimental groups. Artificial rearing of infant rat pups on a HC diet for 8 days lead to a 3.3-fold increase in islet CYO-II mRNA expression compared with mother-fed pups. However, glucose (11 mmol/L) stimulation of cultured isolated islets from young and old rats for 4 days failed to affect the expression level of mitochondrial gene mRNAs. Thus, aging affected the differential expression of CYO-II, NADH-DH4, and ATP-SYN6 mRNAs in rat islets. CYO-II mRNA expression was modulated only in infant rat islets after in vivo administration of carbohydrate.

Aging↗
PubMed2001

Bacteriologic and clinical efficacy of ofloxacin 0.3% versus ciprofloxacin 0.3% ophthalmic solutions in the treatment of patients with culture-positive bacterial keratitis.

PURPOSE: To compare the efficacy and safety of ofloxacin 0.3% ophthalmic solution with ciprofloxacin 0.3% ophthalmic solution in patients with culture-positive bacterial keratitis. METHODS: Patients with a microbiologic diagnosis of bacterial keratitis were included in this double-masked, parallel-group study and were randomized to treatment with either ofloxacin 0.3% or ciprofloxacin 0.3% ophthalmic solution. One drop of the study medication was instilled during the daytime according to the following schedule: every half-hour on study day 1, every hour on days 2 through 4, and every 2 hours on days 5 through 21. Healing, the primary outcome measure, was defined as complete reepithelialization, accompanied by nonprogression of stromal infiltrate for 2 days. Secondary outcome measures included signs and symptoms of infection. Patients were monitored throughout the study period for any adverse events. RESULTS: A total of 217 patients completed the study: 112 were treated with ofloxacin and 105 were treated with ciprofloxacin. Streptococcus pneumoniae was the most commonly encountered pathogen in all patients. Complete corneal reepithelialization occurred in 85% of those treated with ofloxacin and in 77% of those treated with ciprofloxacin (p = 0.32). The average time to corneal ulcer healing was 13.7 days in those treated with ofloxacin and 14.4 days in those treated with ciprofloxacin. Both treatments were well tolerated with no patient discontinuing the study because of side effects. CONCLUSION: Ofloxacin 0.3% and ciprofloxacin 0.3% ophthalmic solutions are effective and safe in the treatment of patients with culture-positive bacterial keratitis.

Adult↗
PubMed2001

Congenital corneal anesthesia: a series of four case reports.

PURPOSE: Discussion of four cases of congenital corneal anesthesia with varied systemic associations and modes of presentation. Classification and systemic associations of congenital corneal anesthesia along with the importance of multi-specialty evaluation of such patients. METHODS: Clinical examination of all four cases and corneal sensation assessment with Cochet-Bonnet esthesiometer. Thorough systemic examination and investigations including serum bio-chemical analysis, roentgenography, ultrasonography, nerve conduction studies, and CT scan of the patients to identify systemic associations. RESULTS: All four patients proved to have bilateral congenital corneal anesthesia with Cochet-Bonnet esthesiometry confirming corneal anesthesia. Systemic examination revealed associated congenital mesenchymal anomalies in the first case. The second case had generalized reduction in pain sensitivity confirmed by nerve conduction studies. The third case was an isolated bilateral congenital corneal anesthesia, while the fourth was a case of congenital trigeminal nerve anesthesia involving all three divisions of both trigeminal nerves. Other causes of corneal anesthesia and self-inflicted corneal injuries were ruled out by clinical multi-specialty evaluation and appropriate investigations. Correct diagnosis and symptomatic treatment aided speedy relief of symptoms of all the patients. CONCLUSION: Congenital corneal anesthesia is a rare condition and is often a diagnostic dilemma. Although more common conditions that cause corneal anesthesia can mislead the clinician, the congenital variant should be kept in mind in any case of intractable corneal ulceration in children. Early diagnosis, symptomatic treatment and measures to prevent further corneal damage will immensely help in retaining useful vision for the affected children.

Child↗
PubMed2001

Programming into adulthood of islet adaptations induced by early nutritional intervention in the rat.

To investigate the influence of a high carbohydrate (HC) intake during the suckling period on pancreatic function in adult life, neonatal rats were artificially reared on a HC milk formula during the preweaning period and then weaned onto lab chow. In the adult HC rat, hyperinsulinemia is sustained by a variety of biochemical and molecular adaptations induced in the HC islets during the suckling period. The adult HC islets showed a distinct left shift in the glucose-stimulated insulin-secretory pattern. HC islets were also able to secrete moderate levels of insulin in the absence of glucose and in the presence of Ca(2+) channel inhibitors. In addition, the mRNA levels of preproinsulin, somatostatin transcription factor-1, upstream stimulatory factor-1, stress-activated protein kinase-2, phosphatidylinositol kinase, and GLUT-2 genes were significantly increased in HC islets. These results show that consumption of a HC formula during the suckling period programs pancreatic islet function in adult rats, resulting in the maintenance of hyperinsulinemia in the postweaning period and eventually leading to the development of obesity in adult life.

Animals↗
PubMed2001

Evaluation of TGF-alpha and EGFR expression in oral leukoplakia and oral submucous fibrosis by quantitative immunohistochemistry.

OBJECTIVE: Oral leukoplakia (OL) and oral submucous fibrosis (OSMF) are clinically distinct preneoplastic states that precede the development of oral squamous cell carcinoma. Recently, attempts are being made to identify specific molecular event(s) as prognostic markers to identify oral precancerous lesions with higher malignant potential. The goal of the present study was to evaluate the expression of EGFR and its ligand TGF-alpha in OL with dysplasia and OSMF as intermediate markers of malignancy by quantitative immunohistochemistry. METHODS: Oral tissues were stained with monoclonal antibodies to TGF-alpha and EGFR. The results were analyzed with Photoquant image analysis software. RESULTS: The expression of TGF-alpha and EGFR was upregulated in OL, OSMF and oral squamous cell carcinomas relative to normal oral mucosa. The area and intensity of staining of TGF-alpha in the proliferative layers (stratum germinativum) increased linearly in OL with mild, moderate and severe dysplasia as compared to control mucosa (p < 0.05). EGFR levels increased linearly in the stratum spinosum in OL with increasing degrees of dysplasia (p < 0.05). In general, the expression of both proteins in OSMF was similar to that in OL with moderate dysplasia. CONCLUSIONS: EGFR and TGF-alpha represent early markers of malignancy in OL with dysplasia. Quantitative measurement of these proteins may provide intermediate endpoints in prospective chemopreventive trials.

Age of Onset↗
PubMed2001

A long-term high-carbohydrate diet causes an altered ontogeny of pancreatic islets of Langerhans in the neonatal rat.

Neonatal rats fed a high-carbohydrate (HC) formula by gastrostomy are hyperinsulinemic but normoglycemic. We determined whether HC formula altered pancreatic islet cell ontogeny. Rats were reared from d 4 on an HC formula or a high-fat formula, or were allowed to suckle naturally, and the pancreata were examined histologically from animals < or =24 d of age. The mean area of individual islets was reduced, but islet number was increased in HC rats compared with mother-fed or high fat-fed animals, which were similar. Islets from HC animals were relatively deficient in alpha cells and had a greater incidence of islet cells with fragmented DNA, indicative of apoptosis. Ductal epithelium, a source of new islets by neogenesis, had a greater incidence of cells staining immunopositive for proliferating cell nuclear antigen, a marker of cell replication, and a lower incidence of apoptosis. The islet cell mitogen and survival factor, IGF-II, had a reduced mRNA expression in whole pancreas from HC animals. The relative area of islet cells demonstrating IGF-II immunoreactivity was reduced in HC-fed rats versus controls, although a greater percentage of ductal epithelial cells were immunopositive. HC formula alters islet cell ontogeny by affecting islet size and number, which may be linked to an altered IGF-II expression.

Animals↗
PubMed2001

Cigarette smoke and asbestos activate poly-ADP-ribose polymerase in alveolar epithelial cells.

BACKGROUND: Cigarette smoke augments asbestos-induced bronchogenic carcinoma in a synergistic manner by mechanisms that are not established. One important mechanism may involve alveolar epithelial cell (AEC) injury resulting from oxidant-induced DNA damage that subsequently activates poly (ADP-ribose) polymerase (PARP), an enzyme involved in DNA repair that can deplete cellular energy stores. We previously showed that whole aqueous cigarette smoke extracts (CSE) augment amosite asbestos-induced DNA damage and cytotoxicity to cultured AEC in part by generating iron-induced free radicals. We hypothesized that CSE increase asbestos-induced AEC injury by triggering PARP activation resulting from DNA damage caused by iron-induced free radicals. METHODS: Aqueous CSE were prepared fresh on the day of each experiment. PARP activity in WI-26 (a type I-like cell line) and A549 (a type II-like cell line) cells was assessed by the uptake of labeled NAD over 4 hours and confirmed on the basis of the reduction of PARP levels in the presence of a PARP inhibitor, 3-aminobenzamide (3-ABA). Cell survival was assessed by trypan blue dye exclusion. RESULTS: Hydrogen peroxide (H2O2; 1-250 microM), CSE (0.4-10 vol%), and amosite asbestos (5-250 micrograms/cm2) each caused PARP activation in WI-26 and A549 cells. The combination of asbestos (5 micrograms/cm2) and CSE (0.04-10%) induced WI-26 and A549 cell PARP activation without evidence of synergism. 3-ABA significantly attenuated WI-26 and A549 cell PARP activity and cell death after exposure to H2O2, CSE, and asbestos. Phytic acid, an iron chelator, catalase, and superoxide dismutase each decreased WI-26 cell PARP activation caused by asbestos and CSE. CONCLUSIONS: CSE and asbestos induced PARP activation in cultured AEC in a nonsynergistic manner. These data provide further support that asbestos and cigarette smoke are genotoxic to relevant lung target cells and that iron-induced free radicals in part cause these effects.

Antioxidants↗
PubMed2001

Use of a cDNA array for the identification of genes induced in islets of suckling rats by a high-carbohydrate nutritional intervention.

Four-day-old rat pups that are raised artificially on a high-carbohydrate (HC) milk formula immediately develop hyperinsulinemia, which persists into adulthood without any further nutritional stimulus. cDNA array analysis was used to identify large-scale changes in gene expression patterns in islets from 12- and 100-day-old HC rats in response to the HC dietary modification during the suckling period. It was observed that the expression of several genes that belong to clusters involved in beta-cell development and/or beta-cell function was significantly upregulated in islets from 12- and 100-day-old HC rats. It is inferred that in addition to predicted changes in gene expression, for example preproinsulin gene, global changes in gene expression contribute to the hyperinsulinemic state in the HC rat.

Aging↗
PubMed2001

The Oregon Health Plan: predictors of office-based diabetic quality of care.

OBJECTIVE: In 1994, the Oregon Health Plan (OHP) expanded basic Medicaid insurance to residents under the federal poverty limit, adopted a prioritized limited benefits package, and converted to managed care. The quality of care in predominantly Medicaid populations with diabetes has not been previously described. In OHP enrollees, we examined predictors of diabetes care based on American Diabetes Association guidelines and described OHP diabetes care compared with national benchmarks. RESEARCH DESIGN AND METHODS: Chart abstraction and Medicaid data for 1995-1996 yielded 996 nonpregnant diabetic patients who were 18-64 years of age. Using HbA1c, lipid panel, and urine protein/microalbumin documentation ordered during the study year, we constructed a standard care (SC) index: SC for all three tests, mixed care (MC) for one to two tests, or no tests documented (NTD). RESULTS: Our sample was predominantly white, 48 +/- 11 years of age, 63% women, with 8 +/- 5 provider visits. Providers ordered HbA1c (70%), urine microalbumin/protein (57%), and lipid panel (41%) tests. Patients distributed into SC (22%), MC (62%), or NTD (16%). Thirteen variables predicted SC. Patients had a higher likelihood of SC if they were 18-24 years of age, had more clinic visits, were on insulin daily, were in several comorbid groups, were enrolled in salaried or capitated health plans, or lived in counties with more hospital beds. Four studies were used as comparable national benchmarks. CONCLUSIONS: Care provided to OHP patients with diabetes compares favorably with national benchmarks. Yet, most OHP patients with diabetes are still not achieving optimal care. Examining predictors of SC may play an important role in further policy development.

Adolescent↗
PubMed2000

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.

Two large-scale yeast two-hybrid screens were undertaken to identify protein-protein interactions between full-length open reading frames predicted from the Saccharomyces cerevisiae genome sequence. In one approach, we constructed a protein array of about 6,000 yeast transformants, with each transformant expressing one of the open reading frames as a fusion to an activation domain. This array was screened by a simple and automated procedure for 192 yeast proteins, with positive responses identified by their positions in the array. In a second approach, we pooled cells expressing one of about 6,000 activation domain fusions to generate a library. We used a high-throughput screening procedure to screen nearly all of the 6,000 predicted yeast proteins, expressed as Gal4 DNA-binding domain fusion proteins, against the library, and characterized positives by sequence analysis. These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. These data reveal interactions that place functionally unclassified proteins in a biological context, interactions between proteins involved in the same biological function, and interactions that link biological functions together into larger cellular processes. The results of these screens are shown here.

Fungal Proteins↗
PubMed2000

The salCAB operon of Azospirillum irakense, required for growth on salicin, is repressed by SalR, a transcriptional regulator that belongs to the Lacl/GalR family.

The salAB genes of Azospirillum irakense KBC1, which encode two aryl-beta-glucosidases, are required for growth on salicin. In the 4-kb region upstream of the salAB genes, two additional genes, salC and salR, were identified. SalC shows characteristics of the outer membrane receptors in the FepA/FhuA family. The salC AB genes are transcribed as a polycistronic mRNA. The salR gene encodes a protein homologous to the LacI/GalR family of transcriptional repressors. Expression of the sal operon, measured by means of a salC-gusA translational fusion in A. irkense KBC1, requires the presence of aryl-beta-glucosides such as arbutin and salicin. Expression is markedly enhanced when a simple carbon source, like glucose, cellobiose or malate, is added to the medium. In a salR mutant, expression of the salC-gusA fusion does not require an aryl-beta-glucoside inducer. Expression of a salR-gusA fusion is constitutive. The product of arbutin hydrolysis (hydroquinone) partly inhibits the expression of a salC-gusA fusion in arbutin- or salicin-containing minimal medium. This effect is independent of SalR. Salicylalcohol, the hydrolysis product of salicin, also partly inhibits salC expression in a SalR-independent fashion, but only in salicin-containing minimal medium.

Amino Acid Sequence↗
PubMed2000

Characterization of commercial and experimental sodium caseinates by multiangle laser light scattering and size-exclusion chromatography.

A range of sodium caseinate samples were characterized by a multiangle laser light scattering (MALLS) system or by the use of MALLS as an on-line detector with size-exclusion chromatography (SEC). Sodium caseinate solutions, analyzed using a MALLS system alone, gave weight-average molar mass (M(w)) values in the range 1200-4700 kDa and z-average root-mean-square radius (R(g)) values ranged from approximately 50 to 120 nm. When these solutions were ultracentrifuged at 90000g for 1 h, a cloudy top layer was formed; the subnatant was carefully removed and analyzed by SEC-MALLS. The M(w) values were found to be in the range approximately 30-575 kDa, and R(g) values ranged from approximately 22 to 49 nm. During SEC, the MALLS system detected some very large-sized material that eluted close to the void volume; this material was hardly detected by the concentration detectors, i.e., ultra-violet (UV) and differential refractive index (DRI). The intensity of the light scattering (LS) signal from this very large sized material was greatly reduced in the subnatant. SEC of sodium caseinate samples revealed two main peaks with M(w) of approximately 420-750 kDa and 39-69 kDa, respectively. The R(g) values were very large for a protein molecule, and initial calculations suggested that the shape of caseinate molecules was likely to be highly elongated.

Caseins↗
PubMed2000

Nitric oxide biomarkers increase during exercise-induced vasodilation in the forearm.

The purpose of the study was to determine if exercise-induced vasodilation was associated with an increase in forearm plasma levels of nitric oxide (NO) biomarkers (NO2- + NO3- and L-citrulline). Twelve healthy subjects (27+/-6 yrs) performed incremental rhythmic forearm exercise with the nondominant hand for 6 min each at 15, 30 and 45% of maximal voluntary contraction (MVC). Forearm blood flow (FBF) was determined in the exercise arm using venous occlusion plethysmography. Blood samples were obtained from the antecubital vein of the exercise and nonexercise arms for the measurement of NO biomarkers. In the exercise arm, FBF increased by a mean of 150%, 335% and 585% above baseline at 15, 30 and 45% of MVC, respectively. (ANOVA, P= 0.0001). Venous plasma NO2- + NO3- levels increased from 24+/-4 micromol/L at baseline, to 29+/-5, 32+/-4 and 3+/-4 micromol/L (ANOVA, P = 0.0001). Venous plasma L-citrulline levels increased from 31+/-5 micromol/L at baseline to 58+/-10, 87+/-7 and 141+/-15 micromol/L (ANOVA, P = 0.0001). There was a linear relationship between FBF and venous plasma NO2- + NO3- (slope= 0.38+/-0.10, P=0.0007) and between L-citrulline, (slope= 5.1 +/-1.3, P = 0.0004). Venous plasma levels of NO2- + NO3- and L-citrulline in the nonexercise arm were unchanged. These results demonstrate that exercise-induced vasodilation in the forearm is associated with forearm plasma levels of NO2- + NO3- and L-citrulline, in vivo markers of NO production.

Adult↗