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Biomedical subjects

I Das

Publications and source records attributed to I Das.

At least 19 recordsLinked to original sources
PubMed2006

Epidemiology, clinical and laboratory characteristics of Staphylococcus aureus bacteraemia in a university hospital in UK.

There has been a persistent increase in the number of meticillin-resistant Staphylococcus aureus (MRSA) and meticillin-susceptible Staphylococcus aureus (MSSA) bacteraemia in the UK. This prospective study included 147 episodes of S. aureus bacteraemia in 139 patients over a 14 month period, from 1 November 2001 to 31 December 2002. Eighty-seven (59%) episodes in 84 patients and 60 (41%) in 56 patients were due to MRSA and MSSA, respectively. An intra-vascular device (29, 33%) and a soft-tissue (15, 25%) source were the commonest identifiable foci for bacteraemia in the MRSA and MSSA groups, respectively. Attributable mortality in the MRSA group was higher than the MSSA group (33% vs 16%; P=0.03) but there was no statistical difference for either attributable (P=0.35) or crude (P=0.39) mortality between the two groups, when adjusted for age, respiratory focus and inappropriate antibiotic therapy. A respiratory source (P=0.02) and inappropriate antibiotic therapy (P=0.02) were associated with attributable mortality in the MRSA group whereas advanced age was the only risk factor (P=0.02) in the MSSA group. The present study shows that S. aureus bacteraemia continues to be a serious infection mostly affecting the elderly and emphasizes the need for improved strategy in the control and management of this condition.

Adolescent↗
PubMed2006

Inversion of magnetoresistance in magnetic tunnel junctions: effect of pinhole nanocontacts.

Inverse magnetoresistance has been observed in magnetic tunnel junctions with pinhole nanocontacts over a broad temperature range. The tunnel magnetoresistance undergoes a change of sign at higher bias and temperature. This phenomenon is attributed to the competition between the spin conserved ballistic transport through the pinhole contact where the transmission probability is close to unity and spin polarized tunneling across the insulating spacer with weak transmittivity.

Journal Article↗
PubMed2002

Carbapenem-resistant Acinetobacter and role of curtains in an outbreak in intensive care units.

Multiple-antibiotic-resistant Acinetobacter baumanii, including meropenem resistance, was first isolated from a patient in the general intensive care unit of a tertiary-referral university teaching hospital in Birmingham in December 1998. Similar strains were subsequently isolated from 12 other patients, including those on another intensive care unit within the hospital. The outbreak followed an increase in the use of meropenem in both the units. Environmental screening revealed the presence of the multiple-resistant Acinetobacter species on fomite surfaces in the intensive care unit and bed linen. The major source appeared to be the curtains surrounding patients' beds. Typing by pulsed field gel electrophoresis demonstrated that the patients' isolates and those from the environment were indistinguishable. Rigorous infection control measures including increased frequency of cleaning of the environment with hypochlorite (1000 ppm) and twice-weekly changing of curtains were implemented, along with restriction of meropenem use in the units. Isolation of the multiple-resistant Acinetobacter spp. subsequently diminished and it was not detected over a follow-up period of 18 months. To our knowledge, this is the first reported outbreak of carbapenem-resistant Acinetobacter spp. from the UK. This outbreak also highlights environmental sources, particularly dry fabrics such as curtains, as an important reservoir for dissemination of acinetobacters.

Acinetobacter↗
PubMed2001

SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation.

Notch receptors and their ligands play important roles in both normal animal development and pathogenesis. We show here that the F-box/WD40 repeat protein SEL-10 negatively regulates Notch receptor activity by targeting the intracellular domain of Notch receptors for ubiquitin-mediated protein degradation. Blocking of endogenous SEL-10 activity was done by expression of a dominant-negative form containing only the WD40 repeats. In the case of Notch1, this block leads to an increase in Notch signaling stimulated by either an activated form of the Notch1 receptor or Jagged1-induced signaling through Notch1. Expression of dominant-negative SEL-10 leads to stabilization of the intracellular domain of Notch1. The Notch4 intracellular domain bound to SEL-10, but its activity was not increased as a result of dominant-negative SEL-10 expression. SEL-10 bound Notch4 via the WD40 repeats and bound preferentially to a phosphorylated form of Notch4 in cells. We mapped the region of Notch4 essential for SEL-10 binding to the C-terminal region downstream of the ankyrin repeats. When this C-terminal fragment of Notch4 was expressed in cells, it was highly labile but could be stabilized by the expression of dominant-negative SEL-10. Ubiquitination of Notch1 and Notch4 intracellular domains in vitro was dependent on SEL-10. Although SEL-10 interacts with the intracellular domains of both Notch1 and Notch4, these proteins respond differently to interference with SEL-10 function. Thus, SEL-10 functions to promote the ubiquitination of Notch proteins; however, the fates of these proteins may differ.

Animals↗
PubMed2000

Trk C receptor signaling regulates cardiac myocyte proliferation during early heart development in vivo.

Neurotrophin-3 (NT-3) is a member of the neurotrophin family of growth factors, best characterized by its survival- and differentiation-inducing effects on developing neurons bearing the trk C receptor tyrosine kinase. Through analysis of NT-3 and trk C gene-targeted mice we have identified NT-3 as critically regulating cardiac septation, valvulogenesis, and conotruncal formation. Although these defects could reflect cardiac neural crest dysfunction, the expression of NT-3 and trk C by cardiac myocytes prior to neural crest migration prompted analysis of cell-autonomous actions of NT-3 on cardiac myocytes. Retroviral-mediated overexpression of truncated trk C receptor lacking kinase activity was used to inhibit activation of trk C by endogenous NT-3, during early heart development in ovo. During the first week of chicken development, expression of truncated trk C reduced myocyte clone size by more than 60% of control clones. Direct mitogenic actions of NT-3 on embryonic cardiac myocytes were demonstrated by analysis of BrdU incorporation or PCNA immunoreactivity in control and truncated trk C-expressing clones. Inhibition of trk C signaling reduced cardiac myocyte proliferation during the first week of development, but had no effect at later times. These studies demonstrate that endogenous NT-3:trk C signaling regulates cardiac myocyte proliferation during cardiac looping and the establishment of ventricular trabeculation but that myocyte proliferation becomes NT-3 independent during the second week of embryogenesis.

Amino Acid Sequence↗
PubMed2000

Trk C signaling is required for retinal progenitor cell proliferation.

Although neurotrophin actions in the survival of specific retinal cell types have been identified, the biological functions for neurotrophin-3 (NT-3) in early retinal development remain unclear. Having localized NT-3 and trk C expression at early developmental stages when retinal neuroepithelial progenitor cells predominate, we sought to modulate NT-3 signaling in these cells by overexpressing a truncated isoform of the NT-3 receptor, trk C. We have demonstrated that this non-catalytic receptor can inhibit NT-3 signaling when coexpressed with the full-length kinase-active trk C receptor. Using a replication-deficient retrovirus to ectopically express the truncated trk C receptor to limited numbers of progenitor cells in ovo, we examined the effects of disrupted trk C signaling on the proliferation or differentiation of retinal cells. Clones expressing truncated trk C exhibited a 70% reduction in clone size, compared with clones infected with a control virus, indicating that inhibition of trk C signaling decreased the clonal expansion of cells derived from a single retinal progenitor cell. Additionally, impaired NT-3 signaling resulted in a reduction of all retinal cell types, suggesting that NT-3 targets retinal precursor cells rather than differentiated cell types. BrdU labeling studies performed at E6 indicate that this reduction in cell number occurs through a decrease in cell proliferation. These studies suggest that NT-3 is an important mitogen early in retinal development and serves to establish the size of the progenitor pool from which all future differentiated cells arise.

Animals↗
PubMed2000

Validation of immunoassays for bioanalysis: a pharmaceutical industry perspective.

Immunoassays are bioanalytical methods in which quantitation of the analyte depends on the reaction of an antigen (analyte) and an antibody. Although applicable to the analysis of both low molecular weight xenobiotic and macromolecular drugs, these procedures currently find most consistent application in the pharmaceutical industry to the quantitation of protein molecules. Immunoassays are also frequently applied in such important areas as the quantitation of biomarker molecules which indicate disease progression or regression, and antibodies elicited in response to treatment with macromolecular therapeutic drug candidates. Currently available guidance documents dealing with the validation of bioanalytical methods address immunoassays in only a limited way. This review highlights some of the differences between immunoassays and chromatographic assays, and presents some recommendations for specific aspects of immunoassay validation. Immunoassay calibration curves are inherently nonlinear, and require nonlinear curve fitting algorithms for best description of experimental data. Demonstration of specificity of the immunoassay for the analyte of interest is critical because most immunoassays are not preceded by extraction of the analyte from the matrix of interest. Since the core of the assay is an antigen-antibody reaction, immunoassays may be less precise than chromatographic assays; thus, criteria for accuracy (mean bias) and precision, both in pre-study validation experiments and in the analysis of in-study quality control samples, should be more lenient than for chromatographic assays. Application of the SFSTP (Societe Francaise Sciences et Techniques Pharmaceutiques) confidence interval approach for evaluating the total error (including both accuracy and precision) of results from validation samples is recommended in considering the acceptance/rejection of an immunoassay procedure resulting from validation experiments. These recommendations for immunoassay validation are presented in the hope that their consideration may result in the production of consistently higher quality data from the application of these methods.

Algorithms↗
PubMed1999

Molecular cloning and expression of adenosine kinase from Leishmania donovani: identification of unconventional P-loop motif.

The unique catalytic characteristics of adenosine kinase (Adk) and its stage-specific differential activity pattern have made this enzyme a prospective target for chemotherapeutic manipulation in the purine-auxotrophic parasitic protozoan Leishmania donovani. However, nothing is known about the structure of the parasite Adk. We report here the cloning of its gene and the characterization of the gene product. The encoded protein, consisting of 345 amino acid residues with a calculated molecular mass of 37173 Da, shares limited but significant similarity with sugar kinases and inosine-guanosine kinase of microbial origin, supporting the notion that these enzymes might have the same ancestral origin. The identity of the parasite enzyme with the corresponding enzyme from two other sources so far described was only 40%. Furthermore, 5' RNA mapping studies indicated that the Adk gene transcript is matured post-transcriptionally with the trans-splicing of the mini-exon (spliced leader) occurring at nt -160 from the predicted translation initiation site. The biochemical properties of the recombinant enzyme were similar to those of the enzyme isolated from leishmanial cells. The intrinsic tryptophan fluorescence of the enzyme was substrate-sensitive. On the basis of a multiple protein-alignment sequence comparison and ATP-induced fluorescence quenching in the presence or the absence of KI and acrylamide, the docking site for ATP has been provisionally identified and shown to have marked divergence from the consensus P-loop motif reported for ATP- or GTP-binding proteins from other sources.

Acrylamide↗
PubMed1999

A comparison of daily CT localization to a daily ultrasound-based system in prostate cancer.

PURPOSE: Daily CT localization has been demonstrated to be a precise method of correcting radiation field placement by reducing setup and organ motion variations to facilitate dose escalation in prostate carcinoma. The purpose of this study was to evaluate the feasibility and accuracy of daily ultrasound-guided localization utilizing daily CT as a standard. The relatively simple computer-assisted ultrasound-based system is designed to be an efficient means of achieving daily accuracy. METHODS AND MATERIALS: After five weeks of conformal external beam radiation therapy, 23 patients underwent a second CT simulation. Prostate-only fields based on this scan were created with no PTV margin. On each of the final conedown treatment days, a repeat CT simulation and isocenter comparison was performed. Ten of the above patients also underwent prostate localization with a newly developed ultrasound-based system (BAT) that is designed to facilitate patient positioning at the treatment machine. The portable system, which electronically imports the CT simulation target contours and isocenter, is situated adjacent to the treatment couch. Transverse and sagittal suprapubic ultrasound images are captured, and the system overlays the corresponding CT contours relative to the machine isocenter. The CT contours are maneuvered in three dimensions by a touch screen menu to match the ultrasound images. The system then displays the 3-D couch shifts required to produce field alignment. RESULTS: The BAT ultrasound system produced good quality images with minimal operator training required. The localization process was completed in less than 5 min. The absolute magnitude difference between CT and ultrasound was small (A/P range 0 to 5.9 mm, mean 3 mm +/- 1.8; Lat. range 0 to 7.9 mm, mean 2.4 mm +/- 1.8; S/I range 0 to 9 mm, mean 4.6 mm +/- 2.8). Analysis confirmed a significant correlation of isocenter shifts (A/P r = 0.66, p < 0.0001; Lat. r = 0.58, p < 0.003; S/I r = 0.78, p < 0.0001) in all dimensions, and linear regression confirmed the equivalence of the two modalities. CONCLUSIONS: Daily CT localization is a precise method to improve daily target localization in prostate carcinoma. However, it requires significant human and technical resources that limit its widespread applicability. Conversely, localization with the BAT ultrasound system is simple and expeditious by virtue of its ability to image the prostate at the treatment machine in the treatment position. Our initial evaluation revealed ultrasound targeting to be functionally equivalent to CT. This ultrasound technology is promising and warrants further investigation in more patients and at other anatomical sites.

Feasibility Studies↗
PubMed1998

Daily CT localization for correcting portal errors in the treatment of prostate cancer.

INTRODUCTION: Improved prostate localization techniques should allow the reduction of margins around the target to facilitate dose escalation in high-risk patients while minimizing the risk of normal tissue morbidity. A daily CT simulation technique is presented to assess setup variations in portal placement and organ motion for the treatment of localized prostate cancer. METHODS AND MATERIALS: Six patients who consented to this study underwent supine position CT simulation with an alpha cradle cast, intravenous contrast, and urethrogram. Patients received 46 Gy to the initial Planning Treatment Volume (PTV1) in a four-field conformal technique that included the prostate, seminal vesicles, and lymph nodes as the Gross Tumor Volume (GTV1). The prostate or prostate and seminal vesicles (GTV2) then received 56 Gy to PTV2. All doses were delivered in 2-Gy fractions. After 5 weeks of treatment (50 Gy), a second CT simulation was performed. The alpha cradle was secured to a specially designed rigid sliding board. The prostate was contoured and a new isocenter was generated with appropriate surface markers. Prostate-only treatment portals for the final conedown (GTV3) were created with a 0.25-cm margin from the GTV to PTV. On each subsequent treatment day, the patient was placed in his cast on the sliding board for a repeat CT simulation. The daily isocenter was recalculated in the anterior/posterior (A/P) and lateral dimension and compared to the 50-Gy CT simulation isocenter. Couch and surface marker shifts were calculated to produce portal alignment. To maintain proper positioning, the patients were transferred to a stretcher while on the sliding board in the cast and transported to the treatment room where they were then transferred to the treatment couch. The patients were then treated to the corrected isocenter. Portal films and electronic portal images were obtained for each field. RESULTS: Utilizing CT-CT image registration (fusion) of the daily and 50-Gy baseline CT scans, the isocenter changes were quantified to reflect the contribution of positional (surface marker shifts) error and absolute prostate motion relative to the bony pelvis. The maximum daily A/P shift was 7.3 mm. Motion was less than 5 mm in the remaining patients and the overall mean magnitude change was 2.9 mm. The overall variability was quantified by a pooled standard deviation of 1.7 mm. The maximum lateral shifts were less than 3 mm for all patients. With careful attention to patient positioning, maximal portal placement error was reduced to 3 mm. CONCLUSION: In our experience, prostate motion after 50 Gy was significantly less than previously reported. This may reflect early physiologic changes due to radiation, which restrict prostate motion. This observation is being tested in a separate study. Intrapatient and overall population variance was minimal. With daily isocenter correction of setup and organ motion errors by CT imaging, PTV margins can be significantly reduced or eliminated. We believe this will facilitate further dose escalation in high-risk patients with minimal risk of increased morbidity. This technique may also be beneficial in low-risk patients by sparing more normal surrounding tissue.

Computer Simulation↗
PubMed1998

Increased arachidonic acid induced platelet chemiluminescence indicates cyclooxygenase overactivity in schizophrenic subjects.

Platelets were found to emit a burst of chemiluminescence during incubation with arachidonic or linoleic acid. This chemiluminescence response may indicate activation of the enzyme prostaglandin synthase in the arachidonate-induced platelet chemiluminescence as it is inhibited by aspirin. Stimulation of platelets with arachidonic acid and linoleic acid induced a concentration dependent chemiluminescence response. Platelets from drug naive schizophrenic subjects showed significantly increased arachidonic acid metabolism compared to control subjects. No significant difference was observed between schizophrenic and control subjects in the chemiluminescence response to linoleic acid. In schizophrenic subjects treated with neuroleptic drugs the overactive arachidonic acid response was normalized. Linoleic acid chemiluminescence response was unaffected by neuroleptic treatment. Hyperactive cyclooxygenase activity may reflect a similar condition in the brain and implicates prostaglandin pathway abnormalities in the pathogenesis of schizophrenia.

Adult↗
PubMed1998

Enterococcal bacteremia in children: a review of seventy-five episodes in a pediatric hospital.

BACKGROUND: Enterococcal bacteremia is being increasingly reported. Although there have been a number of recent studies of enterococcal bacteremia in adults, there are few studies involving children. We carried out a prospective study to determine the epidemiologic, clinical and laboratory characteristics of such bacteremia in children. METHODS: Clinical and microbiologic data were recorded prospectively for all episodes of enterococcal bacteremia occurring during a 3-year period between January 1, 1995, and December 31, 1997. RESULTS: Seventy-five episodes of enterococcal bacteremia occurring in children at our institution during a 3-year period were prospectively analyzed. Serious underlying disease was present in 67 (89.3%) episodes, and in 48 (64.%) episodes patients had received antibiotics during the 2 weeks preceding enterococcal bacteremia. Forty-seven (62.7%) episodes were nosocomial in origin and 26 (34.7%) were polymicrobial. Fifty (66.7%) episodes occurred in children 1 year old or less. A source of bacteremia was identified in 33 (44%) episodes, intravascular device being the most common identifiable source. Of the 73 isolates identified to species level, there were 36 Enterococcus faecium, 36 Enterococcus faecalis and one Enterococcus avium. In 60 (80%) episodes appropriate anti-enterococcal therapy was given. The overall mortality rate was 7.5%. Four clinical patterns of infection were identified: self-limited bacteremia, 16.0%; low grade sepsis with a favorable outcome after specific therapy, 65.3%; severe and prolonged infection associated with a high mortality rate, 14.7%; and fulminant neonatal sepsis in previously healthy babies, 4.0%. CONCLUSION: Enterococcal bacteremia in children comprises a heterogeneous group. Bacteremias that are mild and self-limited and respond promptly to antibiotic therapy appear to be more common in children.

Adolescent↗
PubMed1998

Pharmacokinetics and inflammatory fluid penetration of clinafloxacin.

A single 200-mg dose of clinafloxacin was given orally to each of nine healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharidin-induced inflammatory fluid, and urine over the following 24 h (48 h in the case of urine). The mean maximum concentration in plasma was 1.34 microg/ml at a mean time of 1.8 h postdose. The mean maximum concentration in the inflammatory fluid was 1.3 microg/ml at 3.8 h postdose. The mean elimination half-life of clinafloxacin in plasma was 5.65 h. The overall penetration into the inflammatory fluid was 93.1%, as assessed by determining the ratio of area under the concentration-time curves. Recovery of clinafloxacin in urine was 58.8% by 24 h and 71.8% by 48 h postdose.

Adult↗
PubMed1998

Experience of changing between signal and Bactec 9240 blood culture systems in a children's hospital.

AIM: To compare experience of positive blood cultures in successive years before and after changing from Signal (Unipath) to Bactec 9240 (Becton Dickinson) blood culture systems. METHODS: Analysis of data collected prospectively on 7967 Signal and 7062 Bactec blood culture sets. RESULTS: Significant growths occurred in 5.7% of Signal and 8.9% of Bactec cultures; 33.0% more significant isolates and 24.0% more episodes of bacteraemia were detected in the second year, following introduction of the Bactec system. Inpatient hospital activity increased by 8.2% between the first and second years, although the numbers of blood cultures received actually fell by 11.4%. There were striking increases in numbers of isolates of coagulase negative staphylococci (47.7%) and Enterobacteriaceae (56.8%) from Bactec cultures. Two anaerobic bacteraemias were detected in Signal blood cultures, whereas none was detected by the Bactec system, despite 12.1% of sets including an anaerobic bottle. Of significant positive cultures, 90.2% were detected within one day with the Bactec 9240, compared with only 50.0% of Signal cultures; 20.7% of significant positive Signal blood cultures were detected only on terminal subculture. Microorganisms that were not significant were isolated from 5.1% Signal and 3.8% Bactec cultures. CONCLUSIONS: Compared with the Signal system, the Bactec 9240 offers markedly more rapid and sensitive detection of bacteraemia, together with a lower rate of non-significant isolates. However, using a single PEDS PLUS/F bottle the few episodes of anaerobic bacteraemia that occur in children are likely to be missed.

Bacteremia↗