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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 289 records · Page 16Linked to original sources
PubMed2000

Signal transduction mechanism in human neutrophil: comparative study between the zeta and beta-protein kinase isotypes.

Role of protein kinase C (PKC) isotypes in the regulation of neutrophil function are not clearly known. In the present study we purified the beta-PKC and zeta-PKC isotypes from human neutrophil. Both the isotypes are immunoreactive only to their respective antibodies. Zeta-PKC was further confirmed by RT-PCR using specific primer. Co-factor requirements for both the kinases were found to be different when DG and ceramide were used as second messenger. Selective substrate specificities were determined for both beta and zeta-PKC using isotype specific pseudosubstrates viz., [Ser25]PKC[19-31] and [Ser119]PKC[113-130] respectively. Endogenous protein phosphorylation by purified beta-PKC and zeta-PKC showed their functional differences in neutrophil. Beta-PKC phosphorylated 13, 15, 19, 33, 36, 47, 80 and 92 kDa proteins and zeta-PKC phosphorylated 19, 22, 42, 47, 75 and 87 kDa proteins, only exception was the phosphorylation of 47 kDa protein which had been phosphorylated by both the kinases. Differences in phosphorylation between beta-PKC and zeta-PKC clearly indicate the selective role for these PKC isotypes in the activation sequences of neutrophil.

Base Sequence↗
PubMed2000

Immunization of cross-bred cattle against Hyalomma anatolicum anatolicum by purified antigens.

Extracts prepared from unfed larvae of Hyalomma anatolicum anatolicum were purified by immunoaffinity chromatography using anti-gut IgG as ligand. Affinity purified antigen (Aff-GHLAg) was used to immunize cross-bred (Bos taurus x B. indicus) calves of 6-7 months of age. Immunized calves rejected 70.6% larvae, 54.5% nymphs and 61.9% adults. No significant changes in the engorged weight of females was observed; however, significant decrease in the engorgement weight of larvae and nymphs was recorded. There was a significant decrease in the emerging nymphs (p < 0.05) and adults (p < 0.01) of the tick stages fed on immunized animals. SDS-PAGE analysis revealed three antigenic proteins of 100, 59.4 and 37 kDa responsible for induction of resistance in the host.

Animals↗
PubMed2000

Respiratory syncytial virus upper respiratory tract illnesses in adult blood and marrow transplant recipients: combination therapy with aerosolized ribavirin and intravenous immunoglobulin.

Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in blood and marrow transplant (BMT) recipients. In some subsets of these immunocompromised patients, RSV upper respiratory illnesses frequently progress to fatal viral pneumonia. The frequency of progression to pneumonia is higher during the pre-engraftment than during the post-engraftment period. Once pneumonia develops, the overall mortality is 60-80%, regardless of the treatment strategy. We performed a pilot trial of therapy of RSV upper respiratory illnesses using aerosolized ribavirin and IVIG (500 mg/kg every other day), with the goal of preventing progression to pneumonia and death. Two dosages of ribavirin were used: a conventional regimen (6 g/day at 20 mg/ml for 18 h/day) and a high-dose short-duration regimen (6 g/day at 60 mg/ml for 2 h every 8 h). Fourteen patients were treated for a mean of 13 days (range: 7-23 days). In 10 (71%) patients, the upper respiratory illness resolved. The other four (29%) patients, three of whom were in the pre-engraftment period, developed pneumonia, which was fatal in two. The most common adverse effect was psychological distress at being isolated within a scavenging tent. In conclusion, prompt therapy of RSV upper respiratory illnesses in BMT recipients with a combination of aerosolized ribavirin and IVIG was a safe and promising approach to prevent progression to pneumonia and death.

Adult↗
PubMed2000

The lack of NF-kappa B transactivation and PKC epsilon expression in CD4(+)CD8(+) thymocytes correlates with negative selection.

Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C (PKC) in DP thymocytes, although it was present in mature thymocytes and peripheral T cells. Taken together the results suggest that the lack of PKC epsilon in DP thymocytes could lead to the absence of NF-kappa B activity after antigenic stimulation contributing to negative selection. Cell Death and Differentiation (2000) 7, 1253 - 1262.

Animals↗
PubMed2000

Immunoglobulin G and albumin levels in whole gut lavage fluid provide an objective measure of pouch ileitis.

BACKGROUND: Gut protein loss is a characteristic of inflammatory bowel disease (IBD), and immunoglobulin (Ig) G, albumin and alpha1-antitrypsin concentrations in whole gut lavage fluid (WGLF) correlate with clinical disease activity. If inflammation in ileoanal pouches is similar to IBD, then measurement of protein-losing enteropathy by analysis of WGLF may provide an objective assessment of disease activity in pouches. METHODS: Forty-two patients who had restorative proctocolectomy for ulcerative colitis underwent whole gut lavage with a polyethylene glycol-electrolyte solution. The first clear effluent was filtered, processed by the addition of protease inhibitors and stored at - 70 degrees C. IgG, albumin and alpha1-antitrypsin were assayed in WGLF. The Pouchitis Disease Activity Index (PDAI) was calculated after pouchoscopy and biopsy; the Moskowitz criteria for pouchitis were also applied. RESULTS: There was a significant correlation of the pouchoscopy score and the PDAI with the concentration of WGLF IgG. All patients with 'pouchitis' according to the Moskowitz criteria had a WGLF IgG concentration greater than 10 microg/ml. The WGLF albumin level also showed a significant correlation with the PDAI, but alpha1-antitrypsin concentration did not. CONCLUSION: Analysis of WGLF for IgG and albumin may be useful in the assessment of disease activity in pouch inflammation.

Adolescent↗
PubMed2000

Abnormal intestinal permeability predicts relapse in inactive Crohn disease.

BACKGROUND: Trials of maintenance therapy in quiescent Crohn disease are often underpowered and there is need for objective markers that predict relapse. Intestinal permeability (IP) has been identified as such a marker although it is unknown how this relates to proposed clinical and blood markers of relapse. We aimed to assess the predictive value of intestinal permeability together with clinical and blood markers in a group of patients with inactive Crohn disease. METHODS: We assessed 50 patients with inactive Crohn disease. Inactive disease was defined as a Crohn disease activity index of less than 150. Intestinal permeability was measured by the urinary excretion of lactulose and rhamnose and data relating to postulated clinical and blood markers predictive of relapse were collected. Follow-up for one year assessed whether patients had relapsed or remained in remission. RESULTS: Of the 18 patients with abnormal intestinal permeability, 10 remained in remission and 8 relapsed. Of the 32 with a normal result, 31 remained in remission and 1 relapsed. Patients with abnormal intestinal permeability are significantly more likely to relapse than those with a normal result (chi-square = 14.3; P = 0.0001; relative risk 18). Those that relapsed had shorter disease duration. Multiple regression analysis identifies IP to be an independent variable. CONCLUSIONS: Abnormal intestinal permeability in patients with inactive Crohn disease predicts relapse. This is superior to clinical and blood markers. It is likely that this is due to ongoing subclinical mucosal inflammation. This may be of use when designing clinical trials of maintenance therapy.

Adolescent↗
PubMed2000

Unexpected rapid rise of maternal serum anti-D levels during pregnancy.

Two cases are described where hydrops faetalis developed as a result of very sudden and unexpected rises in serum anti-D levels. In both cases intravascular intrauterine transfusion was employed and a favourable outcome obtained. These cases show that continued vigilance is required even when anti-D levels are low. Weak antibody titres may be detected using enzyme-treated red cells, and failure to use this more sensitive technique meant that in one of the cases the initial weak antibody was not detected. There is currently a debate about the use of this more sensitive test in view of the increased work involved.

Journal Article↗
PubMed2000

Obstetric outcome in women over the age of 40 years.

This is a retrospective review of 109 deliveries during a 5-year period in women aged 40 years or over and the results were compared with other studies in literature. The incidence was 1%. There was no increase in complications of pregnancy though there was an increased caesarean section rate and perinatal mortality rate. It is imperative that all mature pregnant women are managed as a high risk group but we should be mindful of the need to justify intervention in the same way as in the younger age group.

Journal Article↗
PubMed2000

A two-stage variable-stringency semiparametric method for mapping quantitative-trait loci with the use of genomewide-scan data on sib pairs.

Genomewide scans for mapping loci have proved to be extremely powerful and popular. We present a semiparametric method of mapping a quantitative-trait locus (QTL) or QTLs with the use of sib-pair data generated from a two-stage genomic scan. In a two-stage genomic scan, either the entire genome or a large portion of the genome is saturated with low-density markers at the first stage. At the second stage, the intervals that are identified as probable locations of the trait loci, by means of analysis of data from the first stage, are then saturated with higher-density markers. These data are then analyzed for fine mapping of the loci. Our statistical strategy for analysis of data from the first stage is a low-stringency method based on the rank correlation of squared trait-difference values of the sib pairs and the estimated identity-by-descent scores at the marker loci. We suggest the use of a low-stringency method at the first stage, to save on computational time and to avoid missing any marker interval that may contain the trait loci. For analysis of data from the second stage, we have developed a high-stringency nonparametric-regression approach, using the kernel-smoothing technique. Through extensive simulations, we show that this approach is more powerful than is a currently used method for mapping QTLs by use of sib pairs, particularly in the presence of dominance and epistatic effects at the trait loci.

Alleles↗
PubMed2000

Structural and interactional homology of clinically potential trypsin inhibitors: molecular modelling of cucurbitaceae family peptides using the X-ray structure of MCTI-II.

Several trypsin inhibitor peptides (with 28-32 amino acid residues) belonging to the Cucurbitaceae (LA-1, LA-2, MCTI-I, CMTI-I, CMTI-III, CMTI-IV), characterized by a distinctive tertiary fold with three conserved disulphide bonds and with mostly arginine at their active centre, were modelled using the high-resolution X-ray structure of a homologous inhibitor, MCTI-II, isolated from bitter gourd. All the inhibitors were modelled in both their native and complexed state with the trypsin molecule, keeping the active site the same as was observed in the trypsin-MCTI-II complex, by homology modelling using the InsightII program. The minimized energy profile supported the binding constants (binding behaviour) of the inhibitor-trypsin complexes in the solution state. A difference accessible surface area (DASA) study of the trypsin with and without inhibitors revealed the subsites of trypsin where the inhibitors bind. It revealed that the role of mutation of these peptides through evolution is to modulate their inhibitory function depending on the biological need rather than changing the overall structural folding characteristics which are highly conserved. The minor changes of amino acids in the non-conserved regions do not influence significantly the basic conformational and interactional sequences at the trypsin binding subsites during complex formation.

Amino Acid Sequence↗
PubMed2000

Luminal neutrophil migration in ileoanal pouches studied by whole gut lavage.

OBJECTIVE: White cell scintigraphy has shown that neutrophils migrate into the gut wall and lumen in ileoanal pouches. We aimed to establish whether whole gut lavage fluid can be used to investigate intestinal neutrophil migration in ileoanal pouches. DESIGN: A prospective single centre study recruiting consecutive patients. METHODS: Whole gut lavage with polyethylene glycol electrolyte solution was performed in 56 (32 men, 24 women) ileoanal pouch patients who had undergone colectomy for ulcerative colitis; the first clear effluent was collected, processed and stored at -70 degrees C. The fluid was assayed for neutrophil granulocyte elastase using a specific colorimetric assay, IgG, albumin, alpha1-antitrypsin, haemoglobin and cytokines IL-1beta and IL-8 using previously described techniques. Patients' disease activity was characterized following pouchoscopy and biopsy. RESULTS: Patients with pouchitis had significantly higher levels of granulocyte elastase in whole gut lavage fluid compared with those without pouchitis. Patients with detectable granulocyte elastase had higher pouchoscopy score, more severe mucosal neutrophil infiltration and protein loss and bleeding. These patients had significantly higher levels of cytokines IL-1beta and IL-8 in the whole gut lavage fluid, compared with patients with undetectable granulocyte elastase. CONCLUSION: Whole gut lavage fluid samples may provide a useful investigative tool to study mucosal inflammation and luminal neutrophil migration in ileoanal pouches.

Adult↗
PubMed2000

Portal hypertension in the presence of minimal liver damage in Crohn's disease on long-term azathioprine: possible endothelial cell injury.

Azathioprine is a useful agent for the treatment of Crohn's disease but side effects occur in 10% of patients. Hepatic toxicity is well recognized and is usually associated with abnormalities of liver function tests. We describe a female patient who was on azathioprine for the treatment of Crohn's disease for a total of 216 months. She developed portal hypertension complicated by variceal haemorrhage. This required the insertion of a trans-jugular intra-hepatic porto-systemic shunt to control the bleeding. Subsequent histology has shown mild nodular regenerative hyperplasia, and other causes of liver disease have been excluded. The only liver function abnormalities were mild elevation of bilirubin and a low albumin in the later stages.

Adult↗
PubMed2000

Fludarabine induced intestinal pseudo-obstruction: case report and literature review.

Intestinal pseudo-obstruction is a recognized but rare complication of chemotherapy. Vinca alkaloids and cytarabine have been reported to be associated with intestinal pseudo-obstruction. We report a case of fludarabine induced severe intestinal pseudo-obstruction in a 66-year-old man suffering from non-Hodgkin's lymphoma, and describe our successful management of this with a combination of parasympathomimetic and mechanical decompression, after failure of conservative management.

Aged↗
PubMed2000

A cross-sectional and longitudinal study of health-related quality of life after percutaneous gastrostomy.

OBJECTIVE: Although gastrostomy feeding tends to have fewer interruptions than naso-gastric feeding and is cosmetically more acceptable; there is little information on health-related quality of life (HRQoL) in these patients. This study aimed to measure the health-related quality of life of patients after gastrostomy placement. DESIGN: Cross-sectional and prospective cohorts. SETTING: Institutional and community-dwelling patients receiving nutritional support via a gastrostomy. PARTICIPANTS: For the cross-sectional cohort, all individuals who have received a percutaneous gastrostomy from our unit (January 1994-December 1996) were included; 55 of the 102 patients who were still living agreed to follow-up assessment. For the prospective cohort, all patients referred to our unit for percutaneous gastrostomy (March 1997-June 1998) were eligible to participate; 54 of 88 patients (62%) consented and were recruited. METHODS AND OUTCOME MEASURES: A cross-sectional assessment of patient outcome and health-related quality of life using SF-36, the Hospital Anxiety and Depression Scale and a disease-specific questionnaire (PEG-Qu) was carried out in patients in primary health care after receiving a gastrostomy. These assessments, plus the Modified Rankin Scale, were performed on patients studied at the time of gastrostomy placement, and after 1, 6 and 12 months of follow-up. RESULTS: HRQoL questionnaires could be answered in less than half the patients. An overall rating of the effect of the gastrostomy on the patients' and carers' HRQoL showed a positive effect in 55% and 80%, respectively. A positive impression of the gastrostomy by the patient did not necessarily reflect an improvement in their nutritional status. Assessment of HRQoL in a cohort of gastrostomy patients showed deficiencies in the physical domain but not mental function (anxiety or depression), energy or health perception. Neither physical function nor level of cognition at time of gastrostomy placement appear to be able to predict patient survival. Nutritional outcome was not related to HRQoL outcome. CONCLUSION: The majority of patients and carers rate gastrostomy positively. Patients who were 75 years or older had a poorer survival compared to younger patients, but gender, physical or cognitive function had no predictive value on survival.

Age Factors↗
PubMed2000

Differences in intestinal humoral immunity between healthy volunteers from UK and Bangladesh.

BACKGROUND/AIMS: Intestinal morphology has been shown to vary geographically. The impact of this variation on gut mucosal humoral immunity is not well-studied. The technique of peroral whole-gut lavage (WGL) with nonabsorbable cleansing fluid can be utilized for the study of gut immune responses in health and disease. In this study, the WGL technique was employed to compare various gut humoral immune parameters in healthy volunteers from Dhaka in Bangladesh and Edinburgh, UK. METHODS: Eleven healthy individuals (all male, age range 18-32) from Dhaka and 12 healthy individuals (4 male and 8 female, age range 23-48) from Edinburgh underwent WGL with a polyethylene glycol electrolyte-based solution drunk at a rate of 1 l/h. The first clear effluent was collected and processed. An ELISA technique was used to measure total immunoglobulins (A, M and G) and antibodies to bacterial lipopolysaccharide (LPS: endotoxin) ovalbumin and eotaxin. Immunoturbimetry and radioimmunoassy techniques were used to measure protein (albumin and alpha-1 antitrypsin) and eosinophil cationic protein (ECP), respectively, in WGL fluid (WGLF). RESULTS: The total IgA, ECP and eotaxin concentrations in WGLF from the Dhaka group were significantly higher than those of the Edinburgh group (P < 0.03, P < 0.002 and P< 0.005 respectively). The IgA antibody level against the core oligosaccharide of bacterial LPS from several Gram-negative species was significantly higher in the Dhaka group compared to the Edinburgh group (P< 0.0001). Similarly, there was generally higher level of IgA antibody response against the various different LPS core structures of Escherichia coli in the Dhaka group, in particular significantly higher against R1, R3 and R4 LPS cores (P< 0.02, P< 0.03 and P< 0.01 respectively) compared to the Edinburgh group. In contrast to antibacterial antibodies, the IgA and IgM antibodies against ovalbumin were significantly lower in the Dhaka group (P< 0.001 and P< 0.003, respectively) compared to the Edinburgh group. CONCLUSIONS: This study on gut mucosal humoral immunity from two geographically distinct populations suggests that place of residence influences gut mucosal humoral immunity. This difference in stimulation of humoral immunity of the gut might explain different rates of inflammatory bowel diseases in developing and developed countries, and also provides a major challenge for the development of mucosally presented vaccine worldwide.

Adult↗
PubMed2000

Three leflunomide metabolite analogs.

The title compounds, 1-cyano-2-hydroxy-N-[4-(methylsulfonyl)phenyl]but-2-enamide, C(12)H(12)N(2)O(4)S, PHI492, 1-cyano-2-hydroxy-N-[3-(methylsulfonyl)phenyl]but-2-enamide, C(12)H(12)N(2)O(4)S, PHI493, and N-[3-bromo-4-(trifluoromethoxy)phenyl]-1-cyano-2-hydroxybut-2-e namide , C(12)H(8)BrF(3)N(2)O(3), PHI495, are potent inhibitors of Bruton's tyrosine kinase (BTK). The molecular structures of these compounds are similar and they display similar hydrogen-bonding networks and crystal packing. Examination of the crystal-packing interaction in the three compounds reveals an alternating direction of adjacent molecules in the crystalline lattice due to intermolecular cyano-amide hydrogen bonding. PHI492, a positional isomer of PHI493, does not form intermolecular O-H.O hydrogen bonds between molecules and crystallizes in a space group different from that of PHI493 and PHI495. The aromatic ring and the amide group of each molecule form a conjugated pi-system which ensures planarity, with further stabilization gained from intramolecular O-H.O hydrogen bonds.

Antineoplastic Agents↗