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Biomedical subjects

S Nair

Publications and source records attributed to S Nair.

At least 109 records · Page 6Linked to original sources

Nonspecific hyperamylasemia and hyperlipasemia in diabetic ketoacidosis: incidence and correlation with biochemical abnormalities.

OBJECTIVES: Amylase and lipase estimations are the standard tests to diagnose acute pancreatitis (AP). Elevation of amylase and lipase < or = 3 times normal may be nonspecific, but elevation of either one > 3 times normal is reported to be diagnostic of AP. The aim of this study was to evaluate the incidence and magnitude of nonspecific elevations of amylase and lipase in diabetic ketoacidosis (DKA) and to correlate their elevation with known metabolic derangements of DKA. METHODS: A total of 150 consecutive episodes of DKA in 135 patients were evaluated for serum amylase, lipase, and biochemical markers of DKA on admission and 24 h later. Patients were divided according to the following: 1) Clearly nonspecific amylase elevation (CNSA): Amylase elevation < 3 times normal plus normal or < 3 times lipase; 2) Clearly nonspecific lipase elevation (CNSL): Lipase elevation < 3 times normal plus normal or < 3 times amylase; and 3) Probably nonspecific amylase or lipase elevation (PNSA or PNSL): > 3 times elevation of amylase or lipase or both with normal abdominal CT. RESULTS: Elevated amylase and lipase levels ranged from 111 to 1257 IU/L (normal 30-110 IU/L) and 25-529 IU/dl (normal < 24 IU/dl) (CT-proven AP = 16, excluded). Nonspecific amylase elevation (CNSA + PNSA) = 25 (16.6%) cases, CNSA in 10 (6.6% of all DKA or 27% of amylase elevations), and PNSA in 15 (10% of all DKA or 41% of amylase elevations). Nonspecific lipase elevation (CNSL + PNSL) = 36 (24%), CNSL in 23 (15.3% of all DKA or 47% of all lipase elevations), and PNSL in 13 (8.7% of all DKA or 26.5% of all lipase elevations). Multiple regression analyses showed significant correlation of pH and serum osmolality with amylase elevation. Lipase elevation showed positive correlation with serum osmolality alone. CONCLUSIONS: In DKA nonspecific elevations of amylase and lipase occur in 16-25% of cases. Amylase elevation is correlated with pH and serum osmolality, but lipase elevation is correlated with serum osmolality alone. Diagnosis of AP based soley on elevated amylase or lipase, even > 3 times normal, is not justifiable.

Acute Disease↗

ClpC ATPase is required for cell adhesion and invasion of Listeria monocytogenes.

We studied the role of two members of the 100-kDa heat shock protein family, the ClpC and ClpE ATPases, in cell adhesion and invasion of the intracellular pathogen Listeria monocytogenes. During the early phase of infection, a clpC mutant failed to disseminate to hepatocytes in the livers of infected mice whereas the invasive capacity of a clpE mutant remained unchanged. This was confirmed by a confocal microscopy study on infected cultured hepatocyte and epithelial cell lines, showing a strong reduction of cell invasion only by the clpC mutant. Western blot analysis with specific antisera showed that the absence of ClpC, but not that of ClpE, reduced expression of the virulence factors InlA, InlB, and ActA. ClpC-dependent modulation of these factors occurs at the transcriptional level with a reduction in the transcription of inlA, inlB, and actA in the clpC mutant, in contrast to the clpE mutant. This work provides the first evidence that, in addition to promoting escape from the phagosomes, ClpC is required for adhesion and invasion and modulates the expression of InlA, InlB, and ActA, further supporting the major role of the Clp chaperones in the virulence of intracellular pathogens.

Animals↗

Sex differences in fluorouracil-induced stomatitis.

PURPOSE: A meta-analysis of six North Central Cancer Treatment Group (NCCTG) trials involving patients receiving their first ever fluorouracil (5-FU)-based chemotherapy was undertaken to explore the association of sex with reports of the incidence and severity of stomatitis. PATIENTS AND METHODS: Data were obtained on a total of 731 patients (402 men and 329 women). Comparisons of incidence and severity rates and average stomatitis across sex were performed using standard binomial testing and t tests, respectively. Logistic regression analysis and a weighted analysis using data summarized to study level served as evidence of cross-validation. RESULTS: Women reported stomatitis both more often and with greater severity than did men. The incidence of any stomatitis for women was 63% versus 52% for men (P =.002). The incidence of severe or very severe stomatitis for men and women was 22% and 12%, respectively (P =. 0006). On average, women reported stomatitis of roughly 0.4 points higher than men on a 0 to 4 ordinal scale (P <.00001). Comparison of results across treatment and placebo arms was carried out to validate the initial findings. Logistic regression modelling further confirmed the results conditional on the presence of a number of potentially confounding covariates. Women were also 11% more likely than men to experience leukopenia of common toxicity criteria grade >/= 1, (70% v 59%, respectively; P <.00001) and grade 3+ (18% v 11%, respectively; P =.004). CONCLUSION: More women than men reported 5-FU-induced stomatitis. The precise mechanism resulting in different degrees of stomatitis across sex is not evident.

Adult↗

Medial trigonal arteriovenous malformations.

A retrospective analysis of 48 patients of medial paratrigonal arteriovenous malformations (AVMs) which constituted 18% of the total 258. AVMs surgically managed in our institute for 16 years was carried out to study their clinical presentation, radiological features, operative approaches and functional outcome. While hemorrhage was the initial presenting symptom in 35, it was longstanding headache in 10, focal seizures in two and progressive weakness in one. However, 41 of these presented with bleed at the time of admission to our hospital and in 15 there was history of multiple bleeds. Twelve and eleven patients had field cut and hemiparesis respectively. Arterial supply to the malformation was quite uniform with posterior (43 patients) and anterior cerebral (25 patients) being the most frequent source. Venous drainage was predominantly into the galenic system (70%). Preoperative embolization was carried out in six patients. While the AVM was excised through a parasagittal interhemispheric approach in 34 patients, the nidus was approached through a direct transcortical (superior parietal lobule) approach in fourteen patients. There was only one operative mortality. Twelve patients whose preoperative fields were normal developed field cut postoperatively. An improvement of the preoperative field deficit was noted only in one patient. While eight of the ten patients with preoperative weakness improved and remained independent the remaining two were moderately disabled. Only two of the 10 patients who developed postoperative weakness remained severely disabled. Our operative results suggest that these AVMs which are prone to recurrent bleeds can be resected with acceptable morbidity. Hemianopia resulting from bleed or surgery is unlikely to improve.

Adolescent↗

Atypical meningioma: a clinicopathological analysis.

In this retrospective study, 382 operated cases of meningiomas were reviewed. 32 cases (8.3%) were histopathologically classified as atypical meningioma. The anatomical locations and histological features in all the thirty-two cases were correlated with their recurrence rates and biological behaviour. The overall recurrence rate for atypical meningioma within two years was 28% as compared to 9.3% in benign meningiomas. It is being emphasized that an accurate histopathological interpretation of atypical meningioma is essential for predicting the recurrence, biological behavior as well as post-operative management modalities.

Adult↗

Effect of dental health education on the oral health status of a rural child population by involving target groups.

India, a developing country faces many challenges in rendering oral health needs. The majority of Indian population resides in rural areas, of which more than 40% constitute children. These children cannot avail dental facilities due to inaccessibility, financial constraints and stagnation of public dental healthcare services. This entails the health professional to adopt a more practical approach to achieve primary prevention of oral diseases. The most viable solution seems to be dental health education. Documented evidence shows that teachers and parents can augment dental health behaviour. With this background, it was decided to target children in a rural area for comparing the effect of education on children alone, children coupled with teachers and children with the involvement of their parents. An interventional study of 4 months duration was conducted on 430 children, 7 teachers and 100 parents. The parents were educated at home. Clinical oral health status was assessed prior to the delivery of dental health education and also following the intervention. Results showed that the dental health scores improved best in the group of children involving the teachers. It was concluded that teachers could be targeted in order to enhance the effect of dental health education campaigns on children.

Analysis of Variance↗

Calreticulin displays in vivo peptide-binding activity and can elicit CTL responses against bound peptides.

Calreticulin is an endoplasmic reticulum (ER) chaperone that displays lectin activity and contributes to the folding pathways for nascent glycoproteins. Calreticulin also participates in the reactions yielding assembly of peptides onto nascent MHC class I molecules. By chemical and immunological criteria, we identify calreticulin as a peptide-binding protein and provide data indicating that calreticulin can elicit CTL responses to components of its bound peptide pool. In an adoptive immunotherapy protocol, dendritic cells pulsed with calreticulin isolated from B16/F10.9 murine melanoma, E.G7-OVA, or EL4 thymoma tumors elicited a CTL response to as yet unknown tumor-derived Ags or the known OVA Ag. To evaluate the relative efficacy of calreticulin in eliciting CTL responses, the ER chaperones GRP94/gp96, BiP, ERp72, and protein disulfide isomerase were purified in parallel from B16/F10.9, EL4, and E.G7-OVA tumors, and the capacity of the proteins to elicit CTL responses was compared. In both the B16/F10.9 and E.G7-OVA models, calreticulin was as effective as or more effective than GRP94/gp96 in eliciting CTL responses. Little to no activity was observed for BiP, ERp72, and protein disulfide isomerase. The observed antigenic activity of calreticulin was recapitulated in in vitro experiments, in which it was observed that pulsing of bone marrow dendritic cells with E.G7-OVA-derived calreticulin elicited sensitivity to lysis by OVA-specific CD8+ T cells. These data identify calreticulin as a peptide-binding protein and indicate that calreticulin-bound peptides can be re-presented on dendritic cell class I molecules for recognition by CD8+ T cells.

Animals↗

Brain substrate utilisation during acute hypoglycaemia.

AIMS/HYPOTHESIS: Our study was undertaken to examine directly the utilisation of glucose and alternative substrates, in particular amino acids, during hypoglycaemia. METHODS: Catheters were positioned in the jugular venous bulb and an artery in six healthy subjects in the overnight fasted state. Arterio-venous differences for glucose, amino acids, lactate and pyruvate were measured in the basal state, during hyperinsulinaemic euglycaemia and during hyperinsulinaemic hypoglycaemia. The subjects were studied on two different occasions, once during intravenous infusion of amino acids and once during infusion of saline. RESULTS: In the basal state the fractional extraction of glucose across the brain was 10 +/- 2%, glucose uptake accounted for 106 +/- 5% of the brain's oxidative metabolism. There was a small release of lactate and pyruvate. During hyperinsulinaemia glucose uptake continued to account for the entire fuel requirement of the brain. Hyperaminoacidaemia did not result in net amino acid uptake by the brain. During hypoglycaemia (2.4 +/- 0.2 mmol/l) fractional extraction of glucose by the brain increased (p < 0.01) and glucose uptake accounted for 90 +/- 15% of the brain's oxidative metabolism. Uptake of amino acids, lactate or pyruvate could not be detected. CONCLUSION/INTERPRETATION: 1) Brain fractional extraction of glucose increases during hypoglycaemia, 2) hyperinsulinaemia does not change fractional extraction of glucose by the brain, 3) augmented availability of amino acids does not result in brain amino acid uptake during euglycaemia or hypoglycaemia and 4) under the present study conditions glucose remains the major substrate for cerebral metabolism during hypoglycaemia; lactate or pyruvate uptake by the brain can not be detected.

Acute Disease↗

Changing characteristics of a colloid cyst of the third ventricle.

We describe extremely unusual radiological characteristics in a colloid cyst of the third ventricle, where the cyst became dense and its size decreased following a cerebrospinal fluid diversion procedure. Such a course of events has been reported in colloid cysts only twice in the literature.

Adolescent↗

Convenient and versatile DNA extraction using agarose plugs for ribotyping of problematic bacterial species.

We describe a convenient, versatile and safe method for preparing bacterial DNA for ribotyping analysis. In this method, extraction of bacterial DNA from Salmnonella typhi and Burkholderia pseudomallei. and subsequent restriction endonuclease digestion, was performed in agarose blocks/plugs thus minimizing shearing and loss of DNA, problems commonly associated with liquid phase phenol extraction. Digested DNA in the plugs was then electrophoresed directly, transferred to nylon membranes and hybridized with labeled rDNA probes in the usual manner to provide reproducible restriction patterns. This method is particularly useful for bacterial species where standard DNA extraction in the liquid phase using phenol has been problematic (e.g. B. pseudomallei) but can be used for any bacterial species. The DNA extracted within the agarose plugs can be stored for long periods and can be used in other, widely-used typing methods such as pulsed-field gel electrophoresis (PFGE) and PCR-based techniques. Embedding live cells directly in agarose plugs also minimizes the risk of exposure to these virulent human pathogens among laboratory workers.

Bacterial Typing Techniques↗

Cloning and characterization of a cDNA encoding topoisomerase II in pea and analysis of its expression in relation to cell proliferation.

We have isolated and sequenced four overlapping cDNA clones to identify the full-length cDNA for topoisomerase II (PsTopII) from pea. Using degenerate primers, based on the conserved amino acid sequences of other eukaryotic type II topoisomerases, a 680 bp fragment was PCR-amplified with pea cDNA as template. This fragment was used as a probe to screen an oligo-dT-primed pea cDNA library. A partial cDNA clone was isolated that was truncated at the 3' end. RACE-PCR was employed to isolate the remaining portion of the gene. The total size of PsTopII is 4639 bp with an open reading frame of 4392 bp. The deduced amino acid sequence shows a strong homology to other eukaryotic topoisomerase II (topo II) at the N-terminus end. The topo II transcript was abundant in proliferative tissues. We also show that the level of topo II transcripts could be stimulated by exogenous application of growth factors that induced proliferation in vitro cultures. Light irradiation to etiolated tissue strongly stimulated the expression of topo II. These results suggest that topo II gene expression is up-regulated in response to light and hormones and correlates with cell proliferation. Besides, we have also isolated and analysed the 5'-flanking region of the pea TopII gene. This is first report on the isolation of a putative promoter for topoisomerase II from plants.

3' Untranslated Regions↗

Differentiation of Asian rice gall midge, Orseolia oryzae (Wood-Mason), biotypes by sequence characterized amplified regions (SCARs).

We developed a polymerase chain reaction (PCR)-based assay that distinguished five different biotypes of the Asian gall midge (Orseolia oryzae), a major insect pest of rice. A total of 400 random primers were screened using random amplified polymorphic DNAs (RAPDs). Five diagnostic PCR products were isolated, cloned, sequenced and converted to sequence characterized amplified regions (SCARs). Primers specific to these SCARs were able to amplify specific DNA fragments from genomic DNAs of five biotypes of gall midge in a multiplexed-PCR-based assay. The amplified DNA fragments were used as diagnostic markers to identify different biotypes of gall midge. The SCAR primers were also capable of differentiating the Asian from the African rice gall midge (Orseolia oryzivora) as well as detecting a variant of biotype 5 which caused an outbreak in Kerala, India. Unlike the use of plant host differentials and midge feeding behaviour for identifying biotypes, this assay is fast, reliable and unaffected by environmental factors.

Animals↗

ClpE, a novel member of the HSP100 family, is involved in cell division and virulence of Listeria monocytogenes.

We identified, in the facultative intracellular pathogen Listeria monocytogenes, a previously unknown Clp ATPase, unique among the HSP100 proteins because of the presence of a short N-terminal region with a potential zinc finger motif. This protein of 726 amino acids is highly homologous to ClpE of Bacillus subtilis, and is a member of a new subfamily of HSP100/Clp ATPases. The clpE gene is transcribed as a monocistronic mRNA from a typical consensus sigma A promoter. clpE is not stimulated by various stresses, but is upregulated in a clpC mutant. This is the first example of cross-regulation between Clp ATPases. By constructing a clpE mutant of L. monocytogenes, we found that ClpE is required for prolonged survival at 42 degrees C and is involved in the virulence of this pathogen. A double mutant deficient in both ClpE and ClpC was avirulent in a mouse model and completely eliminated in the liver. Electron microscopy studies did not show any morphological alterations in clpE or clpC mutants. In the clpE-clpC double mutant, however, cell division was affected, indicating that ClpE acts synergistically with ClpC in cell septation. These results show that the Clp chaperones play a crucial role in both cell division and virulence of L. monocytogenes.

Adenosine Triphosphatases↗