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S Majumdar

Publications and source records attributed to S Majumdar.

At least 37 records · Page 2Linked to original sources

Activation of MAPK kinase pathway by Gal/GalNAc adherence lectin of E. histolytica: gateway to host response.

Amoebiasis caused by the protozoan parasite Entamoeba histolytica is one of the leading parasitic causes of morbidity and mortality in the developing countries. Among the variety of virulence factors, an adherence lectin (Gal/GalNAc, 260 kDa) has been known to mediate colonization and subsequent host responses. It is a major cell surface antigen which is universally recognized by the immune sera of patients with amoebic liver abscess (ALA). The role of this lectin in cytolysis and phagocytosis of human colonic mucin glycoproteins has also been established. The objective of the present study was to elucidate the signal transduction events induced in response to Entamoeba histolytica derived Gal/GalNAc lectin in the target epithelial cells. We have attempted to define a pathway in target cells that could link this immunodominant antigen to a known biological pathway for target cell activation and triggering of subsequent disease pathology/parasite survival. Lectin stimulated cells showed immediate rise in (Ca2+)i concentration corresponding to 1517.31+/-16.3 nM (approximately) at 0-2 min. The intracellular calcium also extruded from the cells as was measured by increase in calcium green-1 fluorescence. Expression of several protein kinases was checked by western blotting to delineate the signaling pathway. Results showed that the expression of PLA2, PI3K, Ras p21, Ras GAP, ERK-MAPK, p38MAPK and PKC was significantly increased. Expression of Raf-1 and MEK-1 was also found to be significant, as determined by intensity analysis. Overall, it indicated activation of MAPKinase pathway which is implicated in a variety of cellular functions. On the basis of our observations it can be stated that there is a calcium mediated activation of PKC in target cells, by lectin, which inturn activates cyclic nucleotides and other protein kinases. These protein kinases further phosphorylated downstream signals in a sequential manner, thus leading to the activation of MAPKinase cascade. Activation of MAPK cascade, in our studies, is implicated in a variety of physiological cellular functions including apoptosis, proliferation, cytoskeleton rearrangements and permeability changes. However, future screening of the genes responsible for the transcription and translation of new proteins and their biological functions in response to lectin stimulation will prove useful in understanding this host-parasite relationship.

Animals↗

The effect of type-1 fimbrial immunization on gut pathophysiological response in rats infected with Salmonella enterica subsp. enterica serovar Typhimurium.

The pathophysiological mechanism of Salmonella enterica subsp. enterica serovar Typhimurium (Salmonella typhimurium) induced gastroenteritis is controlled by interplay of various cell signaling events. Adherence of this organism through type-1 fimbriae is known to be a vital prerequisite for the establishment of infection. In the present investigation male albino Wistar rats were immunized with purified type-1 fimbriae and challenged intragastrically with S. typhimurium. Electrolyte transport and level of different second messengers were studied in four different groups of animals. Transepithelial fluxes of Na+ and Cl- revealed absorption in immunized-challenged group as observed in case of control and immunized group while secretion was observed in infected group. Ca2+ and 3-0-methyl-D-glucose fluxes did not show any change. Significant increase in the level of intracellular Ca2+, cAMP, membrane form of protein kinase C, prostaglandins, NADPH oxidase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, total oxygen free radicals, reactive nitrogen intermediates, citrulline and lipid peroxidation was found in the infected group. However, in the immunized-challenged group, the values of all the parameters were found to be same as that of control as well as immunized groups. Na+, K(+)-ATPase and calmodulin levels were found to be unaltered in all the groups of animals. Thus, the immunization with type-1 fimbriae has been found to be quite effective leading to the prevention of multiple physiologic derangements in isolated ileal cells suggesting the protective role of the fimbriae.

Animals↗

Monoamine reuptake inhibition and nicotine receptor antagonism reduce amplitude and gating of auditory evoked potentials.

BACKGROUND: Sensory encoding deficits have been extensively studied as endophenotypic markers of schizophrenia using auditory evoked potentials. In order to increase understanding of the neurochemical basis of such deficits, we utilized an animal model to test whether monoamine reuptake inhibition and nicotine receptor antagonism reduce the amplitude and gating of the P20 and N40 auditory components. METHODS: C57BL/6J mice received 12 days of chronic vehicle, bupropion, haloperidol or bupropion plus haloperidol. Auditory evoked potentials were then recorded in alert mice to measure the amplitude and gating of evoked components during a paired click paradigm similar to tasks used to measure the P50 and N100 auditory potentials in schizophrenia. Evoked potentials were recorded prior to and following acute nicotine. RESULTS: Bupropion reduced the amplitude and gating of the N40 evoked potential in mice, similar to the P50 and N100 endophenotypes associated with sensory encoding deficits in schizophrenia. This deficit was fully reversed only by the combination of haloperidol and nicotine, suggesting that dopamine reuptake inhibition and nicotine antagonism both contribute to the observed phenotype. Furthermore, nicotine increased P20 amplitude across all groups supporting a role for nicotine agonists in pre-attentive sensory encoding deficits. CONCLUSIONS: We propose that the combination of monoamine inhibition and nicotine receptor antagonism may serve as a useful model for preclinical screening of pharmaceutical compounds aimed at treating sensory encoding deficits in schizophrenia.

Animals↗

Mode of action of a potentially important excretory--secretory product from Giardia lamblia in mice enterocytes.

Giardia, a common enteric protozoan parasite is a well-recognized cause of diarrhoeal illness. The detailed mechanism of diarrhoea due to this infection is not well understood. A 58 kDa enterotoxin (ESP) was purified from the excretory-secretory product of the parasite. The present study was designed to investigate the mode of action of this enterotoxin of G. lamblia in mice enterocytes. An increase in cyclic adenosine monophosphate level, as well as intracellular Ca2+ concentration, was observed in the ESP-triggered enterocytes. The levels of phospholipase Cgamma1 and inositol triphosphate were found to be upregulated. The activity of protein kinase C (PKC) in the enterocytes was also enhanced following stimulation with the ESP. An increase in the level of reactive oxygen species in ESP-stimulated cells correlated well with the decline in the activity of antioxidant enzymes (superoxide dismutase and catalase). The significantly high levels of nitrite and citrulline indicated the generation of reactive nitrogen intermediates in the ESP-triggered enterocytes. Thus, ESP could induce cross-talk among the different signal transduction pathways in the enterocytes, which could together bring about a common secretory response.

Animals↗

Glutathione S-transferase M1 and T1 null genotype frequency in chronic myeloid leukaemia.

Polymorphisms associated with genes coding for glutathione S-transferase enzymes are known to influence metabolism of different carcinogens and have been associated with incidence of various types of cancer. We have determined the GST M1 and GST T1 'null' genotype frequency in 81 patients with chronic myeloid leukaemia (CML) and 123 racially and geographically matched control individuals by multiplex polymerase chain reaction (PCR). GST M1 null genotype frequencies in CML and controls were 28.4% and 27.7%, respectively. GST T1 null genotype frequencies in CML and controls were 19.8% and 7.3%, respectively. The GST T1 null genotype frequency in CML patients is significantly different from that in controls (odds ratio (OR) 3.12, 95% confidence interval (CI) 1.3-7.45, P=0.008).

Adolescent↗

Body water and plasma volume in severe community-acquired pneumonia: implications for fluid therapy.

OBJECTIVES: To determine changes in total and extracellular body water, plasma volume and sodium in children with severe and very severe pneumonia, and examine the association between these changes and oxygenation. DESIGN: Prospective, observational. SUBJECTS: Fifty children aged 2-59 mths with severe and very severe pneumonia. METHODS: Serum sodium (SNa), plasma osmolality (Posm), urinary sodium (UNa) and osmolality, total body water (TBW), extracellular water (ECW) and plasma volume (PV) were estimated during the acute phase of pneumonia (within 3-6 hrs of presentation) and after recovery. These were correlated with oxygen saturation (SpO(2)) recorded on presentation. RESULTS: All children had cough, fever, tachypnoea and chest-wall indrawing; 70% had inability to feed and 90% were hypoxaemic (SpO(2) < or = 90%). During the acute phase of illness, among the survivors (n=46), mean (SD) ECW and PV were significantly higher than that after recovery [ECW 318 (45) vs 308 (49) ml/kg, PV 53.2 (2.3) vs 52.1 (2.3) ml/kg, p<0.05]. SNa < or = 135 mmol/L was significantly correlated with ECW and PV excess. SpO(2) showed a significant linear relationship with TBW, ECW and PV (r=0.43, 0.46 and 0.42, respectively, p<0.005) and SNa (r= or <0.33, p=0.02). On multiple regression analysis, ECW, blood urea and PV were significant predictors of SpO(2) (combined r=0.63). The four patients who died had significantly higher Posm and blood urea and lower SpO(2) but in a logistic regression model SpO(2) was the only significant predictor of death (odds ratio 0.54, 95% CI 0.32-0.9, p=0.02). CONCLUSION: ECW and PV were moderately increased in severe and very severe pneumonia and the increase correlated with better oxygenation. These findings suggest that fluid retention in response to hypoxaemia is directed towards improving circulating volume. The current practice of fluid restriction in hypoxaemic patients with severe pneumonia might be logical only after correction of hypoxaemia.

Body Water↗

Hyperhomocysteinemia as a risk factor for ischemic stroke: an Indian scenario.

BACKGROUND: Hyperhomocysteinemia has been proposed as an important risk factor for ischemic stroke worldwide, but data available from the Indian subcontinent is scarce. AIM: To study homocysteine levels in patients with ischemic stroke and compare it with age- and sex-matched controls. SETTINGS AND DESIGN: Case-control prospective study. MATERIALS AND METHODS: Fifty-seven patients with ischemic stroke and 30 controls were recruited for the study. They were subdivided into two subgroups (< 40 years and> 40 years of age) and plasma fasting total homocysteine (tHcy) levels were measured. STATISTICAL ANALYSIS USED: Student's 't' test and chi-square test. RESULTS: The tHcy were significantly high in patients with stroke, compared to controls (9.91 +/- 2.25 vs 8.00 +/- 2.74 micromol/l; P vs 8.45 +/- 2.72 micromol/l; P = 0.01) and female patients compared to controls (9.08 +/- 1.81 vs 6.79 +/- 2.60 micromol/l; P = 0.04). The tHcy levels were significantly high in patients with hypertension compared to normotensive patients (10.96 vs 9.49 micromol/l; P = 0.01) and smokers compared to nonsmokers (11.17 vs 9.33 micromol/l; P = 0.01). CONCLUSIONS: Hyperhomo-cysteinemia emerged as an important independent risk factor for ischemic stroke. A strong positive correlation was also observed between hypertension, smoking, and high-tHcy levels in the present study.

Adult↗

Randomized evaluation of fluid resuscitation with crystalloid (saline) and colloid (polymer from degraded gelatin in saline) in pediatric septic shock.

OBJECTIVE: To compare the efficacy of crystalloid (Normal saline) and colloid (polymer from degraded Gelatin in saline Haemaccel) intravenous fluid in restoration of circulating volume in children with septic shock. DESIGN: Prospective, randomized, open-label trial. SETTING: Pediatric Emergency and Intensive Care Unit of a tertiary care referral and teaching hospital. SUBJECTS AND INCLUSION CRITERIA: Sixty patients, between 1 month to 12 years of age, with septic shock, without clinical evidence of organ failure at admission or underlying immunodeficiency. INTERVENTION: Resuscitation with normal saline or polymer from degraded gelatin (Haemaccel) in the boluses rate of 20 mL/kg till hemodynamic stabilization or if central venous pressure (CVP) exceeded 10 mmHg (fluid requirement beyond 40 mL/kg guided by BP and CVP). METHODS: Hemodynamic parameters (heart rate, capillary filling time, pulse volume, and blood pressure) were recorded before and during resuscitation, and then 2 hourly for 12 hours. Central venous pressure line was placed within first hour, soon after starting fluids. Estimation of plasma volume and body water was done at the end of first hour of fluid resuscitation. OUTCOME MEASURES: Hemodynamic stabilization (heart rate, capillary refill time, systolic BP in normal range), plasma volume at the end of fluid resuscitation and incidence of organ dysfunction. RESULTS: 31 patients were randomized to normal saline and 29 to gelatin polymer. Both the groups were similar with respect to age, gender, primary diagnosis, initial hemodynamic parameters and PRISM score. Pneumonia (n = 22; 36%), gut-associated sepsis (n = 13), and dengue hemorrhagic fever (n = 11) were the common primary diagnosis. Initial hemodynamic stabilization was achieved in all. The mean (SD plasma volume (saline--53.4 (2.0 mL/kg, gelatin polymer--53.2 (1.9 mL/kg), extracellular fluid volume, total body water and interstitial fluid volume at the end of first hour of resuscitation were similar. The requirement of inotropes, incidence of organ dysfunction and case fatality rate (Saline--29%, gelatin polymer--31%), were similar in two groups. CONCLUSION: Both normal saline and gelatin polymer solution were equally effective as resuscitation fluid with respect to restoration of plasma volume and hemodynamic stability. Normal saline upto 110 mL/kg, and gelatin polymer solution upto 70 mL/kg may be required in first hour for successful fluid resuscitation of septic shock in children.

Child↗

Treatment of sulphide containing wastewater with sulphur recovery in a novel reverse fluidized loop reactor (RFLR).

A novel aerobic bioreactor, the reverse fluidized loop reactor (RFLR) was tested for recovering sulphur from aqueous sulphide in this study. The RFLR contained buoyant carrier particles on which chemolithotrophic sulphide oxidizing bacteria formed a biofilm, which oxidized sulphide to sulphur and separated from the aqueous phase. The redox potential of the RFLR was regulated to control the oxygenation of sulphide for sulphur production. The RFLR was operated without any pH control and under various controlled pHs. The sulphide removal and nature of products formed under various sulphide loading rates and pH were examined. Under pH uncontrolled state, 95% of sulphur was recovered up to 11 kg sulphide/m3 d. The maximum sulphide loading supplied to the reactor was 30 kg sulphide/m3 d at pH 8, of which 90% was completely oxidized and 65% recovered as sulphur. The decline in bacterial sulphide oxidation leads to chemical oxidation of sulphide and subsequent accumulation of intermediary products such as thiosulphate and polysulphide in the reactor.

Bacteria, Anaerobic↗

Blocked nose and snoring in a 6-year-old boy.

Nasal obstruction, mouth-breathing, snoring and deafness are common symptoms seen in children presenting to the otorhinolaryngology clinic. The aetiopathologies are frequently due to adenotonsillar hypertrophy and otitis media with effusion. Rarely however, nasal obstruction and snoring may be associated with more sinister pathology. We report a case of a child with nasopharyngeal B-cell Non-Hodgkin's lymphoma whose initial symptoms were of nasal obstruction and snoring.

Burkitt Lymphoma↗

Magnetic resonance evaluation of the interrelationship between articular cartilage and trabecular bone of the osteoarthritic knee.

OBJECTIVE: To use high-resolution magnetic resonance imaging (MRI) to determine the relationship between articular cartilage degeneration and trabecular bone changes of the femur, condyles and tibia in human knees with osteoarthritis (OA). METHODS: Subjects were divided into three groups: without OA (OA0), mild OA (OA1) and severe OA (OA2). Sagittal images of the knee (0.234 x 0.234mm2, 2-mm slice thickness) were obtained at 1.5T and used for calculating the volume and thickness of the femoral and tibial cartilage. Axial images (0.195 x 0.195mm2, 1-mm slice thickness) were used for calculating the trabecular bone structure parameters: apparent bone volume fraction, trabecular number, trabecular separation and trabecular thickness. RESULTS: Cartilage volume and thickness were less in patients with OA compared to normal controls (P<0.1). Articular cartilage thinning is associated with bone structure loss in the opposite femoral condyle (P<0.05). In varus OA, there were extensive correlations between medial tibia and medial femoral cartilage degeneration, and loss of bone structure in the lateral tibia and lateral condyle. Additional correlations existed between the compartmental differences (lateral minus medial) of cartilage thickness and bone structure. CONCLUSION: Degradation of articular cartilage within a compartment correlates with a loss of bone structure in the opposite compartment. The correlation between the (L-M) differences corroborates this relationship. Malalignment of the knee due to cartilage degeneration is associated with bone formation in the diseased condyle and bone resorption in the opposite compartment.

Age Factors↗

Entamoeba histolytica Gal/GalNAc lectin depletes antioxidant defences of target epithelial cells.

Among the variety of virulence factors of Entamoeba histolytica, an adherence lectin (Gal/GalNAc, 260 kDa) is known to mediate colonization and subsequent host responses. Gal/GalNAc lectin is universally recognized by the immune sera of patients with amoebic liver abscess. It plays a crucial role in cytolysis and phagocytosis of human and rat colonic mucin glycoproteins. The objective of the present study was to elucidate the role of antioxidants in E. histolytica Gal/GalNAc lectin-induced signals in the target epithelial cells. We have attempted to define a pathway in target cells, Henle-407 cells (human intestinal epithelial cell line), that could link this immunodominant antigen to a known biological pathway for target cell activation and triggering of subsequent disease pathology/parasite survival. Since several workers have demonstrated that cAMP and cGMP may act as important cellular signals for altering ion transport, so in the present study, cAMP and cGMP levels were measured in Henle-407 cells which showed significant increase at 15 min after stimulation. Elevated cAMP and cGMP levels are implicated in altered electrolyte transport and conductance. Results showed that there were increased levels of ROS and RNI which led to reduced activities of antioxidant enzymes--catalase, superoxide dismutase and glutathione peroxidase. Despite the increased glutathione (reduced) levels, the enzymes were not able to combat the damage caused by ROS and RNI. Thus, there was an increased local concentration of the free radicals and reduced activities of all the three enzymes which could damage the target cell in terms of cytoskeleton and permeability changes.

Animals↗

The alteration in signal transduction parameters induced by the excretory-secretory product from Giardia lamblia.

The mechanism by which Giardia lamblia exerts its pathogenicity is likely to be multifactorial. A 58 kDa enterotoxin was purified and characterized from the excretory-secretory product (ESP) of the parasite (Kaur et al. 2001). In the present study an attempt has been made to elucidate the mechanism of action of the ESP, a potentially important enterotoxin. A 41 kDa glycoprotein was identified in the mouse enterocyte membrane fraction with which the ESP interacted in a GM1-specific manner. The GTPase activity was reduced in enterocytes stimulated with the ESP, resulting in an increase in the level of adenylate cyclase-dependent cyclic adenosine monophosphate (cAMP). The activity of protein kinase A (PKA) in the enterocytes was also upregulated after ESP treatment. Ultimately, a significant increase in intracellular Ca2+ concentration and decrease in cytosolic Cl- level were noticed in ESP-stimulated mouse enterocytes. Thus it is possible that the enterotoxic ESP could bind to the 41 kDa glycoprotein (receptor?) on the enterocytes and activate the G-protein-mediated signal transduction pathway resulting in alteration of electrolyte transport.

Animals↗

[Multislice-CT for structure analysis of trabecular bone - a comparison with micro-CT and biomechanical strength].

OBJECTIVES: MS-CT (Multislice-Spiral-CT) has a higher spatial resolution compared to the SS-CT (Singleslice-CT). The purpose of this study was to investigate, if the higher spatial resolution of the MS-CT has advantages for structural analyses in the assessment of osteoporosis. MATERIAL AND METHODS: 20 cylindrical trabecular bone specimens (diameter 12 mm, length 15 - 20 mm) were harvested from formalin-fixed human thoracic spines. All specimens were examined by Micro-CT and quantitative, histomorphologic parameters were determined. Analogous structural parameters were calculated from the high-resolution images acquired by both MS- and SS-CT. Additionally, the BMD (bone mineral density) was measured by QCT (quantitative CT). The maximum compressive strength (MCS) was determined in a biomechanical test. The structural parameters were correlated with the histomorphologic parameters and with the MCS. RESULTS: The parameters bone fraction and trabecular separation correlated significantly in both MS- and SS-CT with the analogous parameters from Micro-CT (r (2) = 0.84, p < 0.01) and the MCS (r (2) = 0.81, p < 0.01). The highest correlation with the MCS was calculated using the trabecular number measured by MS-CT in the superior region near the endplate of the vertebra with the high-resolution kernel U90 u (r (2) = 0.85, p < 0.01). This correlation was significantly higher than the correlation between MCS and BMD (r (2) = 0.49, p < 0.01). CONCLUSION: Micro-CT- and MS-CT-determined structural parameters of the trabecular bone showed significant, high correlations. Thus, a characterisation of the trabecular structure seems to be possible. The biomechanical stability of the bone can also be predicted well. The structural parameters acquired by MS-CT show higher correlations with the MCS than the BMD or structural parameters determined by SS-CT do. In this study MS-CT was best suited to predict biomechanical strength of trabecular bone.

Aged↗

Studies on immunocompetence status in two turkey varieties in India.

(1) Two hundred and twenty-seven adult turkeys of both sexes, of two varieties (104 Black and 123 White) were used to evaluate their immunocompetence status and body weights. (2) Response to sheep red blood cells (SRBC) (humoral immunity) was measured by Haemagglutination (HA) test 5 days post immunisation (dpi) and expressed as log2 values. Mercaptoethanol resistant (MER) antibodies representing IgG were determined by Mercaptoethanol HA test and Mercaptoethanol sensitive (MES) antibodies, representing IgM as the difference in total HA titre and IgG. Serum lysozyme concentrations were estimated by 'Lysoplate assay' and expressed in log2 values. (3) Least squares analysis of variance revealed that the White variety had higher adult body weight (4.788 +/- 0.040 kg) than the Black (3.774 +/- 0.044 kg). Sexual dimorphism was apparent and meals were heavier than females in both varieties. The interaction effect of variety and sex on body weight was also significant. (4) Least squares means for immunological traits, namely, total anti-SRBC antibodies, MER, MES titres and serum lysozyme were 7.161 +/- 0.189, 0.801 +/- 0.071, 6.362 +/- 0.160 and 1.766 +/- 0.043 microg/ml, respectively. The Black variety had a higher MES antibody titre than the White. (5) Sex had an effect on all the immunological traits except on MER titres. Females generally had higher anti-SRBC, MER and MES titres and serum lysozyme. The variety x sex interaction effect was significant for MES titres and serum lysozyme. White males had the lowest MES titres.

Animals↗

Giant combined dermatofibroma with satellitosis.

An unusual giant combined dermatofibroma is reported in a 34-year-old man who presented with skin-coloured swellings on the medial aspect of the left scapula. The plaque was well defined, reddish-brown and 25-30 cm in diameter. It was also tender and indurated. Several similar smaller lesions (satellites) were present around the plaque. Light microscopy of an incisional biopsy from the main lesion showed architectural features of a deep penetrating type of dermatofibroma, with xanthomatous aggregates, myxoid changes and probable myofibroblastic differentiation. Our case represents an extraordinary example of giant combined dermatofibroma with satellitosis. Despite its benign nature, a wide excision is contemplated because of its unsightly appearance and physical discomfort.

Adult↗

Severe sepsis following wound infection by an unusual organism--Clostridium novyi.

We present a case of post-operative wound infection with Clostridium novyi in a non-intravenous drug user. Clinical features included progressive cellulitis despite being on antibiotics, accompanied by hypotension, marked leucocytosis and oedema but minimal fever. While established infection with this organism is associated with high mortality, our patient survived. The administration of clindamycin and intravenous immunoglobulin in addition to early surgical assessment and aggressive debridement of affected tissue may have contributed to this successful outcome. To our knowledge, this is the only reported post-operative wound infection due to this pathogen.

Adult↗