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Biomedical subjects

B Dasgupta

Publications and source records attributed to B Dasgupta.

At least 19 recordsLinked to original sources
PubMed2000

Competitive binding to a charged leucine motif represses transformation by a papillomavirus E6 oncoprotein.

E6 oncoproteins from HPV-16 and bovine papillomavirus type 1 (BPV-1) bind to similar leucine-rich peptides termed charged leucine motifs found on the cellular focal adhesion protein paxillin and the E3 ubiquitin ligase E6AP. BPV-1 E6 (BE6) mutants that do not bind to paxillin are defective at inducing cellular transformation. It is possible, however, that BE6 mutants that do not bind paxillin are defective for transformation for an unrelated reason than the ability to bind to charged leucine motifs. To address the role of BE6 interaction with charged leucine motifs, we fused a BE6-binding charged leucine motif to the amino terminus of BE6, thereby creating an autoinhibitory binding domain. We found that the fusion protein failed to bind to paxillin or transform murine C127 cells. Mutation of the amino terminal binding motif in the fusion protein restored both interaction with paxillin and transformation. This demonstrates that BE6 transformation requires binding to charged leucine motifs on particular cellular proteins and that transformation by papillomavirus oncoproteins can be repressed by competitive interactions with charged leucine motifs.

Amino Acid Sequence↗
PubMed2000

A study of the health assessment questionnaire to evaluate functional status in polymyalgia rheumatica.

OBJECTIVE: To evaluate the Health Assessment Questionnaire (HAQ) in the assessment of functional status, its responsiveness to change with treatment and its correlation with conventional disease activity indices in polymyalgia rheumatica (PMR). METHODS: Newly diagnosed patients with PMR, satisfying modified Jones and Hazleman criteria, were recruited to the study. The clinical assessments, including early morning stiffness (EMS), pain measured on a horizontal 10 cm visual analogue scale (VAS), C-reactive protein (CRP) and the HAQ, were carried out 0, 6, 12 and 24 weeks after treatment had been started. Any comorbid condition likely to affect the HAQ was noted. RESULTS: Eighteen patients completed the 6-month assessment period. These included four males and 14 females, with a mean age of 68.5 years. Pretreatment mean disease activity showed EMS of 68 min, VAS pain of 69 mm, CRP of 46 mg/l and a HAQ score of 1.57. At 6 months, mean EMS had declined to 4 min, VAS pain to 11 mm, CRP to 9 mg/l and the HAQ score to 0.14. Linear regression analysis of HAQ vs EMS, VAS and CRP showed correlation coefficients of 0.72, 0.66 and 0.63, respectively. Standardized response means (SRM), a measure of responsiveness, for HAQ, EMS, VAS and CRP were 3, 1.7, 1. 8 and 1.6, respectively. We assessed each section of the HAQ individually to see if any particular daily activity was more responsive to change. Questions on dressing and grooming, rising and eating were more responsive to change (SRM 2.5, 2.7 and 1.8, respectively) than questions about walking, hygiene, reach, grip and activities (SRM 0.8, 1.4, 1.2, 1.1 and 1.1, respectively). CONCLUSION: The HAQ is useful in the assessment of functional status in PMR, is responsive to change and correlates well with conventional indices of disease activity. However, fixed disabilities like osteoarthritis, shoulder capsulitis and systemic diseases may affect its interpretation. The sections of the HAQ measuring disability related to inflammatory stiffness/proximal involvement showed greater responsiveness to change than other sections, and hence may have a greater role in evaluating disease activity in PMR.

Activities of Daily Living↗
PubMed1999

Biodistribution, radiation dosimetry and pharmacokinetics of 111In-antimyosin in idiopathic inflammatory myopathies.

UNLABELLED: In view of the established role of 111In-antimyosin in the detection of heart muscle pathology, radiation dose estimates were made for this substance. Biodistribution and biokinetic data were obtained from our studies, which failed to show abnormal uptake of 111In-antimyosin in localized sites of skeletal muscle involvement in patients with idiopathic inflammatory myopathies. METHODS: After intravenous administration of 74 MBq (2 mCi) 111In-antimyosin, gamma camera scintigraphy was performed in 12 adult patients with inflammatory muscle disease and in 2 control patients. Six whole-body scans were performed over 72 h, and uptake of 111In-antimyosin in organs was quantified using an attenuation-corrected conjugate counting method. Residence times in source organs were used with MIRDOSE software to obtain radiation dose estimates. Pharmacokinetic parameters were derived from serial whole-blood and plasma 111In concentrations. RESULTS: The tracer cleared slowly from the circulation, and highest organ uptakes were found in the marrow and liver; kidneys showed the highest concentrations. Uptake was also evident in spleen, the facial image and male genitalia. CONCLUSION: For a typical administered activity of 74 MBq 111In-antimyosin, the kidneys receive the highest dose (58 mSv), and the effective dose is 11 mSv. Radioactivity was cleared from plasma at an average rate of 136 mL/h, and the mean steady-state distribution was approximately 5 L plasma.

Adult↗
PubMed1999

Use of a hospital practice management system to provide initial data for a pediatric immunization registry.

An ongoing challenge in the creation of clinical information systems is the capture of structured clinical information from health care providers while avoiding duplicate data recording. Because immunizations are reimbursable medical procedures, practice management systems that already capture such procedures may be used as a source of clinical data for information systems. We instituted a method for capturing such data on one campus of a multi-institution pediatric immunization registry. We measured the effectiveness of this capture by comparing it to manual audits of selected paper charts over 26 months. Of the immunizations documented by chart audit, 39.69% were captured by the practice management system. Of those not captured, we estimate that a substantial portion were immunizations administered elsewhere and as a result not submitted as a claim through the practice management system. In turn, this was affected by a rate of patient disengagement from primary care of 49%. We discuss the issues associated with using claims data to capture clinical information in the setting of an immunization registry and review possible explanations for this data capture rate.

Child↗
PubMed1999

Translating national childhood immunization guidelines to a computer-based reminder recall system within an immunization registry.

To translate national childhood immunization guidelines to a computer-based reminder recall system, hierarchical system architecture design and combined approach of tabular and procedural knowledge representation are taken. Nested branches with hierarchical combinations of single antecedent variables are used to avoid logical incompleteness, redundancy and inconsistency. Mapping to the local electronic medical vocabulary is implemented to facilitate the integration with the local information system architecture. 26 second-level modules with 195 original branches and 121 final branches after pruning are encoded. 99.67% of the reminders are confirmed to be correct by SQL query.

Child↗
PubMed1998

Effects of sputum oscillations and rhDNase in vitro: a combined approach to treat cystic fibrosis lung disease.

Mucolytic treatment with rhDNase is part of the current therapy for cystic fibrosis (CF) lung disease. The Flutter valve, a device for enhancing airway mucus clearance, has recently been approved for use in CF patients. Exhalation through the Flutter valve leads to oscillations of expiratory airflow, improving mucus viscoelasticity and stimulating clearance. The goal of our in vitro study was to evaluate the individual and combined effects of Flutter valve oscillations and rhDNase treatment on the viscoelastic (rheological) properties of CF sputum. Sputum specimens were collected from 19 CF patients and subjected to the following protocols: 1) baseline sample with no treatment applied; 2) application of oscillations generated by airflow through the Flutter valve; 3) incubation at 37 degrees C for 30 min with 10% vol/wt rhDNase (Pulmozyme) to achieve a final concentration of 2.5 microg/mL (approximately 100 nM); 4) combination of Flutter valve oscillations and 10% vol/wt normal saline (0.9% NaCl); 5) combination of Flutter valve oscillations and 10% vol/wt rhDNase at 2.5 microg/mL final concentration. For each protocol, the mucus rigidity index (log G* at 1 rad/s) was measured at baseline and at 30 min. Values are presented as mean+/-SEM. The cough clearability index (CCI) was computed from measurements of mucus viscoelasticity, based on relationships established in model studies. Flutter valve treatment alone did not result in a significant reduction in the rigidity of CF sputum (2.24+/-0.13 vs. 2.11+/-0.13, P=0.19), nor did rhDNase (2.5 microg/mL) alone, although we have previously shown (Pediatr. Pulmonol. 1995; 20:78) that both of these treatments reduce sputum spinnability, which is more sensitive to molecular weight reduction. In comparison to individual treatments, combined treatment with Flutter valve oscillations and rhDNase significantly reduced the mucus rigidity to 1.85+/-0.19 from 2.24+/-0.13 (P< 0.001), consequently increasing the predicted clearability of the sputum (from 1.09+/-0.26 to 1.83+/-0.48, P=0.012). These in vitro results suggest that a combination of biochemical treatment (e.g., DNase) and mechanical oscillation may have a better therapeutic potential for mucus clearance in CF lung disease.

Adult↗
PubMed1998

An initially double-blind controlled 96 week trial of depot methylprednisolone against oral prednisolone in the treatment of polymyalgia rheumatica.

The objective was to compare the efficacy and safety of intramuscular methylprednisolone acetate (i.m. MP) with oral prednisolone (OP) in the treatment of polymyalgia rheumatica (PMR), a common steroid-treated illness where prolonged therapy can lead to steroid side-effects. The cumulative dose with i.m. MP injections given every 3-4 weeks is considerably smaller than that with conventional OP, and may therefore be associated with fewer long-term side-effects. A hybrid design was used with an initial 12 week double-blind placebo-controlled phase followed by an open phase on active treatment up to 96 weeks. The study was multicentre hospital out-patient based and included 60 patients with untreated PMR. In the double-blind phase, either 120 mg 3-weekly i.m. MP or gradually tapering daily OP (initial dose 15 mg) were administered. In the open phase, subjects continued their active treatment with gradual tapering of the steroid dosage. The remission rate at 12, 48 and 96 weeks, and other measures of disease activity, i.e. sedimentation rate, pain and morning stiffness, and percentage of adverse reactions and serious complications such as fractures, were the main outcome measures. Sixty patients entered (30 OP:30 i.m. MP) and 49 (25 OP:24 i.m. MP) completed the study. There were similar remission rates after the double-blind phase (60.6% OP and 66.6% i.m. MP, respectively) and similar disease control in the succeeding open phase. With steroid tapering, the mean erythrocyte sedimentation rate for the entire cohort registered a significant increase in the absence of an increase in symptoms. At 96 weeks, the cumulative mean steroid dose in subjects treated with i.m. MP was equivalent to 56% that of subjects treated with OP. There were eight fractures with OP compared to one on i.m. MP. Mean weight gain was significantly greater with OP than i.m. MP (3.42 vs 0.82 kg, P < 0.005). Minor adverse reactions were similar in both groups apart from slightly increased bruising with i.m. MP. Only patients on OP reported moon face, hypertension, cataracts, back pain and depression, but the numbers were small. It is possible to achieve equivalent long-term disease control in PMR with i.m. MP compared to OP. I.m. MP was associated with far fewer fractures and lesser weight gain, presumably related to lower cumulative dose. These findings may have implications in the steroid treatment of PMR, and other rheumatic and non-rheumatic diseases.

Administration, Oral↗
PubMed1998

Sacral insufficiency fractures: an unsuspected cause of low back pain.

We describe 10 cases of sacral fractures diagnosed within the rheumatology department at Southend Hospital over the last 5 yr. All presented with sudden-onset low back pain. The majority were elderly, frail, with chronic inflammatory disease (six with rheumatoid arthritis, one with polymyalgia rheumatica, one with vasculitis) and had received steroids. Diagnosis was delayed by the inability of plain radiographs to show these fractures and was ultimately demonstrated by technetium scintigraphy/computed tomography scan. We feel that this diagnosis should be considered in elderly patients with rheumatoid arthritis or other risk factors for osteoporosis who present with low back pain and sacral tenderness. Further clues may be parasymphyseal tenderness (suggesting associated pubic ramus fracture), elevated alkaline phosphatase and plain radiograph showing pubic ramus fractures or parasymphyseal sclerosis. Patients with this complication generally have a poor prognosis and two of our patients have died. Seven required in-patient stay (mean 20 days; range 14-41). The mortality, morbidity and costs incurred in management may be comparable to those of femoral neck fractures.

Aged↗
PubMed1998

Sputum rheology changes in cystic fibrosis lung disease following two different types of physiotherapy: flutter vs autogenic drainage.

OBJECTIVE: The aim of the present study was to investigate the efficacy of two frequently used physiotherapies (PTs) for the removal of bronchial secretions in cystic fibrosis (CF) lung disease: autogenic drainage (AD) and the Flutter (Desitin in Germany). AD is believed to improve mucus clearance from peripheral to central airways due to airway caliber changes in combination with a special breathing technique. The Flutter is an easy-to-use physiotherapy device based on oscillations of a steel ball during expiration through a pipe-type device. MATERIALS AND METHODS: To evaluate the acute and chronic physiotherapy effects of these two techniques, 14 CF patients underwent either twice daily AD or Flutter treatment for 4 consecutive weeks in a randomized crossover design. Prior to each therapy interval, for a 1-week wash-out period, no PT was administered, but patients continued regular medication. At the beginning and end of each 4-week interval, pulmonary function was measured before and after an acute 30-min therapy. At the end of the PT session, sputum was collected, weighed, and deep frozen until analyzed. The viscoelasticity of the sputum was evaluated using a magnetic microrheometer. RESULTS: No significant changes were noted for FVC, FEV1, or sputum volume throughout the study. Sputum viscoelasticity (rigidity index), however, was significantly lower (p<0.01) after therapy with the Flutter in comparison with AD, predicting improvements in mucociliary and cough clearability of the secretions. In a companion in vitro experiment, oscillations generated by passing humidified air over CF sputum lining an acrylic tube connected to a Flutter de-ice were found to decrease sputum elasticity, as measured by a filancemeter. These findings suggest that applied oscillations are capable of decreasing mucus viscoelasticity within the airways at frequencies and amplitudes achievable with the Flutter device, and provide direct evidence that PT can reduce the viscoelasticity of sputum.

Adult↗
PubMed1998

Design and implementation of a multi-institution immunization registry.

One of every four children in the USA is underimmunized. Surveys of children in New York City have documented rates of appropriate immunization as low as 37% in certain populations in northern Manhattan. In response to this, government and private agencies have undertaken efforts to improve immunization rates. As part of one such multiinstitution effort in northern Manhattan, we have begun implementation of a computer-based immunization registry. Key features of this registry system include adaptation of legacy software in order to perform initial capture of data in electronic format; design of a user interface using a World Wide Web server that provides data review and capture functions with appropriate security; implementation of a registry database with links to the server, communication links between hospital registration systems, a Master Patient Index, community providers and the central registry; and integration of decision support in the form of Medical Logic Modules encoded in the Arden Syntax. We discuss our design of this multi-institution immunization registry and implementation efforts to date.

Child↗
PubMed1997

Purification and biochemical characterization of a protein-palmitoyl acyltransferase from human erythrocytes.

Protein palmitoylation involves the post-translational attachment of palmitate in thioester linkage to cysteine residues of proteins. The labile nature of the thioester linkage makes possible the palmitoylation-depalmitoylation cycles that have emerged in recent times as additions to the repertoire of cellular control mechanisms. However, detailed understanding of these cycles has been limited by the lack of knowledge of the transferases and thioesterases likely to be involved. Here, we describe the purification of a protein-palmitoyl acyltransferase (PAT) from human erythrocytes. PAT behaved as a peripheral membrane protein and catalyzed the attachment of palmitate in thioester linkage to the beta-subunit of spectrin. On SDS-polyacrylamide gel electrophoresis, PAT appeared as a 70-kDa polypeptide. Antibody against this polypeptide could immunodeplete PAT activity from the crude extract, confirming the assignment of the 70-kDa polypeptide as PAT. PAT-mediated spectrin palmitoylation could be inhibited by nonradioactive palmitoyl-, myristoyl-, or stearoyl-CoA. The apparent Km for palmitoyl-CoA was 16 microM.

Acylation↗
PubMed1997

Effects of inflammation and treatment on bone turnover and bone mass in polymyalgia rheumatica.

OBJECTIVE: Polymyalgia rheumatica (PMR) has an abrupt onset of inflammatory symptoms, making it a useful model for studying the effects of inflammation in bone. PMR requires corticosteroid treatment, which may itself have a detrimental effect on bone. This study used serially measured biochemical markers of bone turnover and bone density to address the relative contributions of systemic inflammation and corticosteroid therapy to bone loss. METHODS: Fifty untreated patients with PMR were randomized to receive oral prednisolone or intramuscular methylprednisolone. Biochemical bone markers (pyridinoline [PYR], deoxypyridinoline [DPYR], procollagen type I carboxy-terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months. RESULTS: The median disease duration at presentation was 12 weeks (range 5-32 weeks). Levels of urinary crosslinks were increased in patients with untreated PMR compared with controls (PYR 74.9 +/- 30.0 nmoles/mmole creatinine, DPYR 14.6 +/- 6.4 nmoles/mmole creatinine [mean +/- SD]; P = 0.0001); the PICP level was normal (115.0 +/- 39.0 microg/liter). With treatment, the crosslinks levels fell and PICP levels rose within 6 months (P = 0.01). Bone resorption (PYR) correlated with untreated disease activity (erythrocyte sedimentation rate [ESR]) (r = 0.5, P = 0.003) and with interleukin-6 levels (r = 0.48, P = 0.05). There was a significant reduction in BMD of both the hip and the spine after 12 months of treatment (P = 0.0002), with no difference between treatment groups. As the steroid dosage was reduced, bone mass improved. Initial ESR influenced the percent change in BMD at 1 year (r = 0.35, P = 0.05), while cumulative steroid dose, mean ESR, and type of steroid used did not. CONCLUSION: Inflammation in PMR increases bone resorption and appears to have a more detrimental effect on bone than does low-dose corticosteroid. If corticosteroids can be tapered and discontinued, bone loss in PMR can be a transient phenomenon.

Adrenal Cortex Hormones↗
PubMed1997

Polyarteritis nodosa and the antiphospholipid syndrome.

We describe a case of classical polyarteritis nodosa (PAN) with visceral aneurysms presenting with renal infarction and hypertension. The female patient also had all the laboratory features of the antiphospholipid syndrome (APS) and 2 months into her illness developed a large iliofemoral thrombosis. She responded well to immunosuppressive therapy and anti-coagulation. Repeat arteriogram showed regression of the visceral aneurysms. The link between PAN and APS, and the therapeutic dilemma posed by this association, are discussed.

Aneurysm↗
PubMed1997

The sequential analysis of T lymphocyte subsets and interleukin-6 in polymyalgia rheumatica patients as predictors of disease remission and steroid withdrawal.

CD4 and CD8 T lymphocyte subsets, the late T cell activation marker, HLA-DR, and serum interleukin-6 (IL-6) levels of 57 polymyalgia rheumatica (PMR) patients were followed over 2 yr to investigate whether they could be used to predict the safe withdrawal of steroid therapy. Cell phenotypes were studied by flow cytometry and IL-6 levels by ELISA. %CD8 cells were reduced below the normal range in PMR patients prior to steroid therapy. In 56% of patients, the %CD8 T lymphocytes failed to return to normal levels when quiescent disease allowed cessation of steroid therapy. Activated CD8 T cells, as detected by HLA-DR positivity, were above the normal range at the initiation of therapy and showed a negative correlation with %CD8 T cells. The serum concentration of IL-6 fluctuated over 24 months, and the correlation between IL-6 and erythrocyte sedimentation rate (ESR) seen prior to treatment was not seen at later intervals. The %CD8 T cell and serum IL-6 levels are not a good indicator of disease activity in PMR and are, therefore, unable to predict the safe withdrawal of steroids.

Administration, Oral↗
PubMed1997

Rheology of cystic fibrosis sputum after in vitro treatment with hypertonic saline alone and in combination with recombinant human deoxyribonuclease I.

Treatment with recombinant human deoxyribonuclease I (rhDNase) is currently used as therapy for cystic fibrosis (CF) lung disease. Hypertonic saline (HS) acts as an expectorant promoting mucus secretion and augmenting the volume of sputum. We evaluated the individual and combined effects of HS and rhDNase in vitro on the viscoelasticity of CF sputum. Sputum samples were collected from nine CF patients to use for in vitro testing. Aliquots of CF sputum (0.20 to 0.40 g) were subjected to the following protocols: (1) negative control sample without any treatment; (2) positive control sample, adding 10% volume of normal saline (0.9% NaCl); (3) application of hypertonic saline (HS-3% NaCl); (4) combining approximately 100 nM concentration of rhDNase with protocols 2 and 3. The samples in protocols 2 through 4 were incubated for 30 min at 37 degrees C. For each protocol, CF sputum was analyzed at baseline and at 30 min for spinnability by filancemeter and viscoelasticity by magnetic microrheometry. Spinnability decreased for the sputum samples that were treated with rhDNase, in combination with either HS or normal saline. Treatment with HS alone and combined treatment with rhDNase and HS decreased log G* (the principal viscoelasticity index) to the same degree. Saline alone and rhDNase in normal saline both increased the predicted cough clearability of the sputum; however, the combined treatment with rhDNase and hypertonic saline had the best overall effect on cough clearability. The change in predicted mucociliary clearability, although greatest after HS, was not significant. These in vitro results suggest that combined treatment with rhDNase and HS should be evaluated further as a potential mucotropic approach to augment the clearance of purulent sputum in CF lung disease.

Adolescent↗
PubMed1996

Reduction in viscoelasticity in cystic fibrosis sputum in vitro using combined treatment with nacystelyn and rhDNase.

The objective of this study was to evaluate the individual and combined effects of Nacystelyn (NAL) and rhDNase in vitro on the rheological properties of cystic fibrosis (CF) sputum. Sputum samples were collected from 11 CF patients and subjected to the following protocols: 1) negative control sample without any treatment; 2) positive control sample incubated with 0.02 ml of normal saline; 3) incubation of CF sputum with 0.02 mL DNase (25 micrograms/mL in normal saline) at 37 degrees C to achieve 2.5 micrograms/g final sputum concentration (approximately 100 nM); 4) incubation of CF sputum with 0.02 mL NAL (30.9 micrograms/mL in normal saline) at 37 degrees C to achieve 3.09 micrograms/g final sputum concentration (10 microM); and 5) combination of protocols 3 and 4 with half the concentration of each drug. The samples in protocols 2 through 5 were incubated for 30 minutes at 37 degrees C. For each protocol, spinnability by filancemeter and viscoelasticity (log G*) by magnetic microrheometer were measured at baseline and 30 minutes. Treatment of the sputum with rhDNase alone or NAL alone decreased spinnability more than control treatment with saline. Combining NAL with rhDNase at half the concentration of each drug significantly decreased spinnability more than either treatment by itself. There were no significant changes in log G* or the derivative parameters, mucociliary clearability index (MCI) and cough clearability index (CCI). The enhanced reduction in sputum spinnability by the combination of NAL and rhDNase indicates additative effects between these two mucolytic treatments. These results suggest that combined treatment with rhDNase and NAL should be considered as a potential therapy for CF patients.

Acetylcysteine↗