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Biomedical subjects

M Biswas

Publications and source records attributed to M Biswas.

At least 19 recordsLinked to original sources
PubMed2005

Long-term remission following withdrawal of dopamine agonist therapy in subjects with microprolactinomas.

OBJECTIVE: Reports suggest that up to 70% of patients with microprolactinomas treated with dopamine agonist therapy may achieve long-term normoprolactinaemic remission following drug withdrawal. Yet, there is no consensus on the duration of therapy nor is therapeutic interruption universally practised. We have assessed remission rates in a large cohort of treatment-naive subjects with microprolactinomas. Subjects received dopamine agonist (DA) therapy with either cabergoline or bromocriptine for a period of 2 to 3 years in the majority of cases, followed by a trial of treatment withdrawal. DESIGN: Retrospective analysis of clinic records of 89 patients (mean age 32.7 +/- 8.4 years, 84 women and 5 men) who had received either cabergoline (n = 67) (0.5-3 mg weekly) or bromocriptine (n = 22) (2.5-10 mg daily) for a mean duration of 3.1 years. RESULTS: Following withdrawal of therapy, 57 subjects developed recurrence (64%) and the mean time to recurrence was 9.6 months (range 1-44 months), while 32 subjects (36%) remained in remission beyond 1 year (mean 3.6 years, range 1-7 years). There was no difference in remission rates between subjects treated with cabergoline (n = 21) and bromocriptine (n = 11), but a direct relationship between pretreatment prolactin concentration and risk of recurrent symptomatic hyperprolactinaemia was observed. No subjects developed clinical features to suggest tumour expansion following therapeutic discontinuation. CONCLUSIONS: This study confirms that abrupt withdrawal of chronic dopamine agonist therapy, following 2 to 3 years of treatment is safe and associated with long-term remission in 30-40% of subjects with microprolactinomas. This therapeutic strategy is convenient and applicable in clinical practice.

Adolescent↗
PubMed2004

Bilateral adrenal enlargement and non-suppressible hypercortisolism as a presenting feature of gastric cancer.

In patients with cancer, adrenal enlargement due to either metastatic disease or diffuse non-metastatic hyperplasia is increasingly recognized with modern imaging techniques. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by non-suppressible hypercortisolism, has also been described in neoplasia in the absence of ectopic adrenocorticotrophic hormone (ACTH) production. In the majority of cases of malignancy-associated hypercortisolism, it might be expected that the presence of malignant disease would be clinically apparent, thus rendering a detailed endocrinological evaluation of the HPA axis unnecessary. However, in the present case we describe a patient with occult malignancy presenting with bilateral adrenocortical enlargement and non-suppressible hypercortisolism that was not due to the ectopic ACTH syndrome. There were no clinical Cushingoid features other than hypertension and new-onset diabetes mellitus. Detailed diagnostic investigations for the possibility of Cushing's syndrome were performed before the underlying diagnosis of gastric adenocarcinoma eventually became apparent. Characteristics and potential mechanisms of non-suppressible hypercortisolism in cancer are discussed. We believe that this scenario will occur with greater frequency in the future, given the increasing early use of sophisticated high-resolution imaging for the evaluation of suspected intra-abdominal pathology.

Adenocarcinoma↗
PubMed2003

Life-threatening thrombotic complications of relative polycythaemia.

Relative polycythaemia refers to raised haematocrit with normal red cell mass. Plasma volume may be reduced. This condition is associated with acute hypoxia, smoking, alcohol and diuretics. We describe two life-threatening thrombotic events in two patients with relative polycythaemia under age 40 years. The first had myocardial infarction and on admission haemoglobin was 21.6 g dL-1. The second developed pulmonary embolism and haemoglobin was 19.1 g dL-1. Both patients received antithrombotic measures and isovolumetric venesection. Sixteen patients (age <40 years) who attended our accident and emergency department in 1 year had a haemoglobin level of >18.0 g dL-1. Recognition of relative polycythaemia in at risk-individuals may help reduce thrombotic risk.

Adult↗
PubMed2003

Pneumococcal necrotizing fasciitis in a patient with Type 2 diabetes.

Necrotizing fasciitis (NF) is a rare and often fatal soft-tissue infection involving the superficial fascial layers of the extremities, abdomen or perineum. Progression to septic shock can occur very rapidly with its associated high morbidity and mortality. NF is usually caused by beta haemolytic streptococci; less often a poly-microbial isolate is the cause. It typically occurs in patients with some degree of immune dysfunction. We present a case of severe pneumococcal necrotizing fasciitis in an obese patient with Type 2 diabetes. There was no history of trauma or evidence of diabetes-related complications. The initial presentation was with features of septic arthritis of the left knee, which subsequently progressed to NF. Differentiation from cellulitis is often difficult in the early stages. Invasive pneumococcal infections are extremely rare, with only a few reported in the literature. Moreover, our case highlights the need to consider other differential diagnoses (and to look out for complications) in patients with diabetes, especially if there is little clinical response to the initial treatment.

Adult↗
PubMed2002

Interactive InterPro-based comparisons of proteins in whole genomes.

MOTIVATION: The SWISS-PROT group at the EBI has developed the Proteome Analysis Database utilizing existing resources and providing comprehensive and integrated comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archaea and eukaryotes. The Proteome Analysis Database is accompanied by a program that has been designed to carry out interactive InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.

Computational Biology↗
PubMed2001

The InterPro database, an integrated documentation resource for protein families, domains and functional sites.

Signature databases are vital tools for identifying distant relationships in novel sequences and hence for inferring protein function. InterPro is an integrated documentation resource for protein families, domains and functional sites, which amalgamates the efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. Each InterPro entry includes a functional description, annotation, literature references and links back to the relevant member database(s). Release 2.0 of InterPro (October 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification encoded by a total of 6804 different regular expressions, profiles, fingerprints and Hidden Markov Models. Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1,000,000 hits from 462,500 proteins in SWISS-PROT and TrEMBL). The database is accessible for text- and sequence-based searches at http://www.ebi.ac.uk/interpro/. Questions can be emailed to interhelp@ebi.ac.uk.

Databases, Factual↗
PubMed2001

Proteome Analysis Database: online application of InterPro and CluSTr for the functional classification of proteins in whole genomes.

The SWISS-PROT group at EBI has developed the Proteome Analysis Database utilising existing resources and providing comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archaea and eukaryotes (http://www.ebi.ac. uk/proteome/). The two main projects used, InterPro and CluSTr, give a new perspective on families, domains and sites and cover 31-67% (InterPro statistics) of the proteins from each of the complete genomes. CluSTr covers the three complete eukaryotic genomes and the incomplete human genome data. The Proteome Analysis Database is accompanied by a program that has been designed to carry out InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.

Animals↗
PubMed2001

Application of InterPro for the functional classification of the proteins of fish origin in SWISS-PROT and TrEMBL.

InterPro (http://www.ebi.ac.uk/interpro/) is an integrated documentation resource for protein families, domains and sites, developed initially as a means of rationalizing the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. It is a useful resource that aids the functional classification of proteins. Almost 90% of the actinopterygii protein sequences from SWISS-PROT and TrEMBL can be classified using InterPro. Over 30% of the actinopterygii protein sequences currently in SWISS-PROT and TrEMBL are of mitochondrial origin, the majority of which belong to the cytochrome b/b6 family. InterPro also gives insights into the domain composition of the classified proteins and has applications in the functional classification of newly determined sequences lacking biochemical characterization, and in comparative genome analysis. A comparison of the actinopterygii protein sequences against the sequences of other eukaryotes confirms the high representation of eukaryotic protein kinase in the organisms studied. The comparisons also show that, based on InterPro families, the trans-species evolution of MHC class I and II molecules in mammals and teleost fish can be recognized.

Animals↗
PubMed2001

Clustering and analysis of protein families.

Various sequence-motif and sequence-cluster databases have been integrated into a new resource known as InterPro. Because the contributing databases have different clustering principles and scoring sensitivities, the combined assignments complement each other for grouping protein families and delineating domains. InterPro and new developments in the analysis of both the phylogenetic profiles of protein families and domain fusion events improve the prediction of specific functions for numerous proteins.

Amino Acid Motifs↗
PubMed2000

Focus group discussions in medical research.

Qualitative research methods have recently started to gain popularity in social and health sciences for determining a more holistic view of peoples' perceptions about health. Focus group discussions are frequently used to obtain perspectives and attitudes of people about issues, seek explanations for behavior, triangulate data obtained through other qualitative methods and generate hypotheses. To facilitate clinicians to comprehend the use of focus group methodology in the clinical field, the meaning, purpose, advantages, limitations and quality assurance measures of focus group discussions are described. The general requirements and the method for conducting focus groups are briefly explained. In addition, key issues that could be addressed by focus group methodology have also been highlighted.

Focus Groups↗
PubMed2000

Quantitative vs qualitative research methods.

Quantitative methods have been widely used because of the fact that things that can be measured or counted gain scientific credibility over the unmeasurable. But the extent of biological abnormality, severity, consequences and the impact of illness cannot be satisfactorily captured and answered by the quantitative research alone. In such situations qualitative methods take a holistic perspective preserving the complexities of human behavior by addressing the "why" and "how" questions. In this paper an attempt has been made to highlight the strengths and weaknesses of both the methods and also that a balanced mix of both qualitative as well as quantitative methods yield the most valid and reliable results.

Data Collection↗
PubMed2000

InterPro--an integrated documentation resource for protein families, domains and functional sites.

MOTIVATION: InterPro is a new integrated documentation resource for protein families, domains and functional sites, developed initially as a means of rationalising the complementary efforts of the PROSITE, PRINTS, Pfam and ProDom database projects. RESULTS: Merged annotations from PRINTS, PROSITE and Pfam form the InterPro core. Each combined InterPro entry includes functional descriptions and literature references, and links are made back to the relevant parent database(s), allowing users to see at a glance whether a particular family or domain has associated patterns, profiles, fingerprints, etc. Merged and individual entries (i.e. those that have no counterpart in the companion resources) are assigned unique accession numbers. Release 1.2 of InterPro (June 2000) contains over 3000 entries, representing families, domains, repeats and sites of post-translational modification (PTMs) encoded by 6581 different regular expressions, profiles, fingerprints and Hidden Markov Models (HMMs). Each InterPro entry lists all the matches against SWISS-PROT and TrEMBL (more than 1000000 hits from 264333 different proteins out of 384572 in SWISS-PROT and TrEMBL).

Computational Biology↗
PubMed1999

Prognostic role of serum prostatic acid phosphatase for 103Pd-based radiation for prostatic carcinoma.

PURPOSE: To establish the prognostic role of serum enzymatic prostatic acid phosphatase (PAP) in patients treated with palladium (103Pd) and supplemental external beam irradiation (EBRT) for clinically localized, high-risk prostate carcinoma. METHODS AND MATERIALS: One hundred twenty-four consecutive patients with Stage T2a-T3 prostatic carcinoma were treated from 1992 through 1995. Each patient had at least one of the following risk factors for extracapsular disease extension: Stage T2b or greater (100 patients), Gleason score 7-10 (40 patients), pretreatment prostate specific antigen (PSA) >15 ng/ml (32 patients), or elevated serum PAP (25 patients). Patients received 41 Gy conformal EBRT to a limited pelvic field, followed 4 weeks later by a 103Pd boost (prescription dose 80 Gy). Biochemical failure was defined as a PSA greater than 1 ng/ml (normal <4 ng/ml). RESULTS: The overall, actuarial freedom from biochemical failure at 4 years after treatment was 79%. In Cox-proportional hazard multivariate analysis, the strongest predictor of failure was elevated pretreatment acid phosphatase (p = 0.02), followed by Gleason score (p = 0.1), and PSA (p = 0.14). CONCLUSION: PAP was the strongest predictor of long-term biochemical failure. It may be a more accurate indicator of micrometastatic disease than PSA, and as such, we suggest that it be reconsidered for general use in radiation-treated patients.

Acid Phosphatase↗
PubMed1999

A database analysis of potential glycosylating Asn-X-Ser/Thr consensus sequences.

An analysis of the frequency of occurrence of various residues at position X was carried out on the consensus glycosylating sequence Asn-X-Ser/Thr using the PDB three-dimensional database. 488 non-homologous proteins bearing 696 Asn-X-Ser/Thr (X not equal Pro) sequences were analysed. More than 65% of Asn residues, when they occur as part of the consensus sequence, lie on the surface of the protein, implying a potentiality for glycosylation. A deviation parameter (DP) was calculated as a measure of preferential (positive) or non-preferential (negative) selection. At the X position in the consensus-sequence segment, the amino acids Gly, Asn and Phe have statistically significant positive DP values. The high value of DP for Asn is a consequence of the preferential occurrence of homodoublets, while for Phe it may be a consequence of the stacking interaction of the aromatic ring with the glycan. Gly at the X position in the consensus glycosylating sequence may be functionally significant owing to its preference and its high percentage of occurrence in proteins. The Ramachandran (Phi,Psi) angles around Gly in the consensus sequence show clustering in the region which is disallowed for non-glycyl residues. In this region, a hydrogen bond between the side chain of Asn and the peptide backbone/side chain of Ser/Thr is possible, reflecting a positional as well as a conformational role in the consensus glycosylating sequence. For the 44 confirmed N-glycosylating sequences, an in-depth analysis of the (Psi(N), Phi(X), Psi(X), Phi(S/T)) dihedral angles, which position the side chains of Asn and Ser/Thr, shows that these can be grouped into nine conformational states. In most cases, a direct or water-mediated hydrogen bond between OD1 of Asn and OG of Ser/Thr is possible, reflecting the possible importance of this hydrogen bonding in the glycosylation process.

Amino Acid Sequence↗
PubMed1997

Determinants of backbone packing in globular proteins: an analysis of spatial neighbours.

This study attempts to examine the pattern and variability of backbone packing density in protein structures. A carefully selected non-redundant data set of known protein structures is analyzed in terms of amino-acid composition and the preference of individual amino acids to fall into regions of low, medium or high density depending on the number of observed non-sequence spatial neighbours. The relationship of the backbone packing density to a number of properties such as the hydrophobicity, non-bonded energies and secondary structural features of the amino acids are examined. The correlation between the average percentage composition and the percentage composition in regions corresponding to different levels of packing density of the proteins is evaluated. These studies are extended to the family of globins whose amino-acid sequences have diverged retaining the same three-dimensional structure during evolution. The significance of high-backbone-density regions in this family has become apparent as due to helix/helix packing. Further, the variation in the amino-acid composition in different contact regions of globin proteins follows the same pattern found for the general data set.

Journal Article↗