Search PubMed⌕ Search

Biomedical subjects

S Mukherjee

Publications and source records attributed to S Mukherjee.

At least 55 records · Page 3Linked to original sources
PubMed2003

Pegylated interferon for recurrent hepatitis C in liver transplant recipients with renal failure: a prospective cohort study.

BACKGROUND: Hepatitis C (HCV) universally recurs following orthotopic liver transplantation (OLT), representing an important cause for retransplantation. Although it is often treated with interferon and ribavirin, ribavirin is contraindicated in the presence of renal failure. In this setting of renal failure, pegylated-interferon monotherapy may be useful for recurrent HCV in liver transplant patients. METHODS: Between June 2001 and November 2002, patients with recurrent HCV were screened to determine if they were eligible for treatment. Renal failure was defined as serum creatinine greater than 1.8 mg/dL. HCVRNA and liver biopsies were performed prior to treatment, end of treatment (EOT) and 6 months after EOT for those who were HCV-RNA negative at EOT. Patients were followed prospectively after starting weekly pegylated-interferon alpha 2b 1.0 microg/kg (Schering-Plough, Kenilworth, NJ, USA). RESULTS: Among the 45 patients with recurrent HCV screened, 9 were eligible, including 8 men and 1 woman of average age 55 years. Eight patients were intolerant to the treatment requiring discontinuation within the first 3 months. Two patients developed a sustained response to HCV eradication. One patient who completed treatment has normal liver tests but is still viremic. CONCLUSIONS: Pegylated-interferon alpha 2b is poorly tolerated in liver transplant recipients with recurrent HCV and chronic renal failure. Larger, prospective studies are required to determine the optimum duration of treatment and the impact of treatment on histology and quality of life.

Adult↗
PubMed2003

Analysis of haemophilia B database and strategies for identification of common point mutations in the factor IX gene.

Haemophilia B is an X-linked recessively inherited bleeding disorder caused by heterogeneous mutations spanning the entire factor IX gene. As spontaneous germ-line mutations are known to occur mostly at CpG dinucleotides in the FIX gene, control of the disease would require continuous carrier detection and mutation screening. Identification of point mutations, the most common type of mutation in FIX gene, is more challenging compared with deletion and insertion mutations. We examined the haemophilia B database to identify specific nucleotides in the FIX gene that are mutated in relatively large number of patients and the variability (if any) in the mutational hotspots at CpG dinucleotides. It was found that while mutations responsible to account for all 2348 haemophilia B patients covered 20% of the FIX cDNA, only 1% of the cDNA involving mostly CpG dinucleotides accounted for mutation in 42.41% of the patient pool. Thus, only 27 nucleotides need to be investigated to identify the common point mutations, among which 15 are predicted to undergo change in restriction sites on mutation. It is interesting to note that seven nucleotides occurring in CpG dinucleotides do not have any reported mutation despite each of those being predicted to harbour mutation as a result of transition and having mutations recorded in the database for the neighbouring nucleotides. Strikingly large number of mutation in codon 296 causing T to M change in catalytic domain originally proposed to be the result of the founder effect also contains largest number of haplotype suggesting recurrence of de novo mutation.

DNA, Complementary↗
PubMed2003

Serum levels of low molecular weight advanced glycation end products in diabetic subjects.

AIMS: One of the principal theories of the development of diabetic complications proposes that increased levels of advanced glycation end products (AGE) are formed in diabetes by prolonged exposure of proteins, lipids and nucleotides to glucose. Such AGEs may contribute to the development of diabetic complications by a number of mechanisms. Circulating AGEs can be detected in serum, and in the present study, we analysed the clinical correlates of circulating serum low molecular weight AGE (LMW-AGE). METHODS: Serum LMW-AGE was measured in 106 non-diabetic and 499 diabetic subjects using fluorescence spectroscopy. Results were calibrated against an in-house AGE albumin preparation, and expressed as absolute fluorescence units (AFU). RESULTS: Serum LMW-AGE values were significantly higher in diabetic than non-diabetic subjects [median 7.5 (range 0-595.5) vs. 5.3 (1.0-15.5) AFU, P<0.01]. In the normal subjects, there were significant correlations between serum LMW-AGE and age (r=0.42, P<0.01) and serum creatinine (r=0.39, P<0.01). In the diabetic patients, serum LMW-AGE correlated significantly with age (r=0.315, P<0.01), systolic blood pressure (r=0.141, P=0.002), serum creatinine (r=0.449, P<0.01) and urinary albumin/creatinine ratio (ACR) (r=0.265, P<0.01). There was no correlation between serum LMW-AGE and HbA1c. On regression analysis, with serum LMW-AGE as the dependent variable, serum creatinine emerged as the most significant factor (t=8.1, P<0.01), followed by age (t=4.0, P<0.01) and ACR (t=2.9, P=0.004). There was no significant difference in serum LMW-AGE between those with and without retinopathy or in those with vascular disease. CONCLUSIONS: We conclude that circulating LMW-AGEs are increased in diabetic subjects. The major determinant appears to be renal dysfunction in the form of raised albumin/creatinine ratio or creatinine. There was no association with other markers of vascular disease or presence of diabetic complications.

Diabetes Mellitus, Type 1↗
PubMed2003

The significance of cardiac doses received during chemoradiation of oesophageal and gastro-oesophageal junctional cancers.

AIM: Although radiation-induced cardiotoxicity has been described in patients with breast cancer and Hodgkin's disease, the effect of oesophageal radiotherapy on the heart has not been evaluated. This study was designed to evaluate the dose received by the heart during chemoradiotherapy (CT-RT) for oesophageal cancer, to assess its impact on cardiac function, and explore methods of reducing this dose. METHODS: Cardiac doses were calculated from dose-volume histograms in 15 patients with carcinoma of mid and lower oesophagus undergoing combined technique treatment, in whom pre- and post-treatment multigated acquisition scans were available. Chemotherapy consisted of cisplatin and 5-fluorouracil with or without paclitaxel. The radiotherapy was delivered in two phases to a total dose of 45-50 Gy in 25 fractions. RESULTS: There was a significant reduction in median ejection fraction after CT-RT (63% to 58%, P = 0.003). The median dose received by the heart using three-dimensional conformal technique was 27.4 Gy (interquartile range 25.8-34.2 Gy). If shielding blocks were not used, as would be the case with conventional planning, the median dose would have been 35 Gy (interquartile range 28.2-37.7 Gy), which is significantly higher (P = 0.002). The use of a three-field technique throughout treatment also reduced the median cardiac dose from 27.4 Gy to 22.7 Gy (P = 0.001) and the volume of heart receiving 70% of total dose from 63.8% to 25% (P = 0.001). CONCLUSION: This study highlights the significant dose of radiation received by the heart during oesophageal CT-RT, with consequent reduction in cardiac ejection fraction. Conformal radiotherapy reduces cardiac doses received. The cardiac, as well as the pulmonary, side effects of CT-RT needs to be borne in mind, especially when using this treatment before radical surgery.

Adult↗
PubMed2002

Excited state proton transfer reaction of two new intramolecularly hydrogen bonded Schiff bases at room temperature and 77K.

Two new orthohydroxy Schiff bases, 7-phenylsalicylidene benzylamine (PSBA) and 7-ethylsalicylideneaniline (ESA) have been synthesized. The excited state intramolecular proton transfer (ESIPT) and the structure of PSBA and ESA in its crystalline form and in the solvents n-hexane, n-heptane and 1,4-dioxane have been investigated by means of absorption, emission and nanosecond spectroscopy at room temperature and 77K. One ground state species has been detected both in neutral and basic solutions of both PSBA and ESA: the cis-enol form with an intramolecular hydrogen bond. The ESIPT and formation of keto tautomer are evidenced by a large Stokes shifted emission (approximately 12000 cm(-1)) at room temperature only in the case of ESA. On the other hand the keto tautomer is the predominant species at 77K in a solid matrix and as a solid sample at room temperature both in the case of ESA and PSBA. In the case of both ESA and PSBA the more intense, higher energy emission is due to the species which has not undergone ESIPT and attributed mainly due to cis-enol form. The trans-enol form is also observed by changing the excitation wavelength. Both the compounds are found to undergo a structural change to a zwitterionic and intermolecular hydrogen bonded form in the presence of a strong base like triethylamine. From the nanosecond measurements and quantum yield of fluorescence we have estimated the decay rates of proton transfer reaction in the case of PSBA. Our theoretical calculation at the AM1 level of approximation shows that the ground singlet state has a rather large activation barrier both in the case of PSBA and ESA. The barrier height is much lower on the corresponding excited singlet surface only in the case of ESA. The process is predicted to be endothermic in the ground state and exotherrmic in the excited singlet state.

Benzylamines↗
PubMed2002

Communicating about pupils in mainstream school with special health needs: the NHS perspective.

AIM: To add to previous research carried out with young people, parents and teachers, by investigating health staff's perspectives on the difficulties, and possibilities for, achieving good communication with school staff with regard to children in mainstream school with a chronic illness or physical disability. RESEARCH DESIGN AND METHODS: A qualitative research study was carried out in one NHS Trust. Twenty semi-structured interviews were carried out with a purposive sample of health staff to cover the spectrum of professionals who have responsibility for meeting the needs of children with a chronic illness or physical disability in mainstream schools (paediatricians, school doctors, school nurses, specialist nurses, health visitors, GPs, speech and language therapists, paediatric occupational therapists, paediatric physiotherapists, clinical psychologists and psychiatrists). RESULTS: The extent to which health professionals communicated with school staff, and the way in which they went about it, varied widely. Communication was facilitated by joint meetings, shared documentation, and local policy development. Sources of difficulty in communication between health and education staff were: the parent as a conduit of information; the practical difficulties of arranging meetings; and lack of knowledge about other professionals' roles. The ethos of the school with regard to health matters, and the flow of information within health services, also had an impact on the communication process. Participants' recommendations focused on two key issues: clarification of the roles of health and education staff with regard to this group of pupils; and how information should flow from health to school staff. DISCUSSION: Many of the findings parallel the previous research with teachers, indicating agreement between professionals from different agencies about aspects of the communication process which are problematic and require attention. The findings suggest that improving communication requires both joint work between health and education staff, and improvements to practice within each agency.

Child↗
PubMed2002

STD treatment for men in rural and urban Zimbabwe: choice of practitioner, perceptions of access and quality of care.

STD treatment choices and perceptions of treatment services (access, quality of care) by Zimbabwean men are examined in 2 settings: Mbare, a district within the capital city Harare, and Gutu, a rural town. Data collection included a survey of 457 men 18 years of age or older (from a stratified systematic sample), focus groups and key informant interviews. Of 220 cases of self-reported genital symptoms, 81.4% were treated by allopathic practitioners, 9% by traditional/faith healers, 8.6% by the subject, a friend or another person; 1.4% were not treated. Traditional/faith healers were consulted primarily for symptoms involving pain or discomfort rather than ulcers or exudation. Disrespect by the health care provider and consultations that were not private were cited as problems by a small minority of subjects. Significantly more respondents in Mbare than in Gutu had been prevented from obtaining the STD treatment they desired at some point in their life because of cost of treatment (chi(2)=5.23, P=0.02). Given the current deteriorating economic situation in Zimbabwe, cost of treatment may become an even more important impediment in the future.

Adult↗
PubMed2002

Left sided cervical and thoracic malignant extra-adrenal pheochromocytoma.

Extra-adrenal Pheochromocytomas are rare entities. High index of suspicion among diastolic hypertensives followed by screening test for 24-hour urinary catecholamine level helps in diagnosis. 123I MIBG scintigraphy is specific for tumour localisation and surgical debulking of tumour or 131I MIBG therapy are alternative modes of treatment.

3-Iodobenzylguanidine↗
PubMed2001

Multiclass cancer diagnosis using tumor gene expression signatures.

The optimal treatment of patients with cancer depends on establishing accurate diagnoses by using a complex combination of clinical and histopathological data. In some instances, this task is difficult or impossible because of atypical clinical presentation or histopathology. To determine whether the diagnosis of multiple common adult malignancies could be achieved purely by molecular classification, we subjected 218 tumor samples, spanning 14 common tumor types, and 90 normal tissue samples to oligonucleotide microarray gene expression analysis. The expression levels of 16,063 genes and expressed sequence tags were used to evaluate the accuracy of a multiclass classifier based on a support vector machine algorithm. Overall classification accuracy was 78%, far exceeding the accuracy of random classification (9%). Poorly differentiated cancers resulted in low-confidence predictions and could not be accurately classified according to their tissue of origin, indicating that they are molecularly distinct entities with dramatically different gene expression patterns compared with their well differentiated counterparts. Taken together, these results demonstrate the feasibility of accurate, multiclass molecular cancer classification and suggest a strategy for future clinical implementation of molecular cancer diagnostics.

Biomarkers, Tumor↗
PubMed2001

The white morphotype of Mycobacterium avium-intracellulare is common in infected humans and virulent in infection models.

Isolates of Mycobacterium avium-intracellulare (MAI) form multiple colony types named red-opaque, white-opaque, red-transparent (RT), and white-transparent (WT). The newly discovered WT morphotype is multidrug resistant relative to other variants in vitro. To determine whether the WT morphotype occurs in humans, 32 MAI-positive clinical samples from 2 sites were plated directly onto indicator agar without prior passage in vitro. WT was the predominant morphotype in 26 (81%) of these samples and was absent in only 2 samples. WT variants grew better than isogenic RT variants in mouse and human macrophage models of infection, and RT clones that passed through such systems underwent rapid shifts to the WT morphotype. The RT morphotype was heterogeneous with regard to infectivity. In summary, the white morphotype was common in humans and was favored in disease models. It may play an important role in the establishment and persistence of MAI infection.

Animals↗
PubMed2001

Cholesterol depletion induces large scale domain segregation in living cell membranes.

Local inhomogeneities in lipid composition play a crucial role in regulation of signal transduction and membrane traffic. Nevertheless, most evidence for microdomains in cells remains indirect, and the nature of membrane inhomogeneities has been difficult to characterize. We used lipid analogs and lipid-anchored proteins with varying fluidity preferences to examine the effect of modulating cellular cholesterol on domain formation. We show that lowering cholesterol levels induces formation of visible micrometer-scale domains in the plasma membrane of several mammalian cell types with complementary distributions of fluorescent lipid analogs with preferences for fluid or ordered domains. A uniform distribution is restored by cholesterol repletion. Unexpectedly, cholesterol depletion does not visibly alter the distribution of a crosslinked or uncrosslinked glycosylphosphatidylinositol-anchored protein (the folate receptor). We also examined the effect of varying cholesterol content on the cold Triton X-100 solubility of several membrane constituents. Although a cholesterol analog, dehydroergosterol, and a glycosylphosphatidylinositol-anchored protein are largely retained after extraction, a lipid analog with saturated 16-carbon acyl chains is largely removed when the cellular cholesterol level is lowered. This result indicates that after cholesterol depletion molecules in the more ordered domains can be extracted differentially by cold nonionic detergents.

Animals↗
PubMed2001

Membrane immunoglobulins are stabilized by interchain disulfide bonds occurring within the extracellular membrane-proximal domain.

Membrane-bound immunoglobulins have, in addition to the transmembrane and cytoplasmic portions, an extracellular membrane-proximal domain (EMPD), absent in the secretory forms. EMPDs of immunoglobulin isotypes alpha, gamma, and epsilon contain cysteines whose role has so far not been elucidated. Using a genetic strategy, we investigated the ability of these cysteines to form disulfide bridges. Shortened versions of human membrane immunoglobulins, depleted of cysteines known to form intermolecular disulfide bonds, were constructed and expressed on the surface of a B-cell line. The resulting membrane proteins contain a single chain fragment of variable regions (scFv) linked to the dimerizing domain from the immunoglobulin heavy chains (CH3 for alpha and gamma or CH4 for epsilon isotypes), followed by the corresponding EMPD and the transmembrane and cytoplasmic domains. The two functional membrane versions of the epsilon chain, containing the short and long EMPD, were analyzed. Our results show that the single cysteine within alpha1L and gamma1 EMPD and the short version of epsilon EMPD form an interchain disulfide bond. Conversely, the cysteine resident in the epsilon transmembrane domain remains unreacted. epsilon-long EMPD contains four cysteines; two are involved in interchain bonds while the remaining two are likely forming an intrachain bridge. Expression of a full-length membrane epsilon heavy chain mutant, in which Cys(121) and Cys(209) within domain CH2 (involved in interchain bridges) were mutated to alanines, confirmed that, within the complete IgE, EMPD cysteines form interchain disulfide bonds. In conclusion, we unveil evidence for additional covalent stabilization of membrane-bound immunoglobulins.

Amino Acid Sequence↗
PubMed2001

Novel lipase-catalysed enantioselective deacetylation of (+/-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine.

(+/-)-5-Acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine has been synthesised by a highly diastereoselective [3+2] cycloaddition reaction between alpha-(4-fluorophenyl)-N-phenylnitrone and vinyl acetate in good yield. Candida rugosa lipase catalyses the deacetylation of this (+/-)-5-acetoxyisoxazolidine in a highly enantioselective fashion in diisopropyl ether containing n-butanol affording (-)-5-acetoxy-3-(4-fluorophenyl)-2-phenylisoxazolidine in 43% yield and >99% ee.

Acetylation↗