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Biomedical subjects

A Dey

Publications and source records attributed to A Dey.

At least 19 recordsLinked to original sources
PubMed2006

Soluble phosphorylated fms-like tyrosine kinase III. FLT3 protein in patients with acute myeloid leukemia (AML).

FLT3 ligand (FL) has a significant role in the proliferation and differentiation of hematopoietic cells. Mutations in the FLT3 receptor gene have been reported in 30% of patients with AML. We investigated whether abnormal phosphorylation of FLT3 may be more common in AML. We evaluated FLT3 protein and its phosphorylation in the plasma from 85 patients with AML, 16 patients with myelodysplastic syndrome (MDS) and 5 patients with acute lymphoblastic leukemia (ALL). There were no significant differences in the level of plasma FLT3 protein level in the different diseases (p=0.57). AML patients had a significantly higher level of phospho-FLT3:FLT3 ratio (p=0.02). FLT3-ITD and FLT3 point mutations were present in 27 (32%) of the AML patients. Phosphorylated FLT3 was significantly higher in the plasma from patients with FLT3 mutation (p=0.002). Overall, there was no correlation between survival and the plasma level of FLT3 protein or its phosphorylated form. However, amongst the patients without FLT3 mutations, those with a higher level of phosphorylated FLT3 had a significantly shorter duration of remission (p=0.04). Other mechanisms may be responsible for abnormal phosphorylation of FLT3 and inhibitors of FLT3 should also be investigated in patients without mutations.

Adolescent↗
PubMed2006

Transfusion transmitted leishmaniasis: a case report and review of literature.

Leishmaniasis is caused by the infection of haemoparasite Leishmania . The disease is a major public health problem in at least 88 countries, including India. Various species of Leishmania are involved in causing this disease. In India, Leishmania donovani species causes visceral leishmaniasis or kala-azar. The parasite is mainly transmitted from infected to uninfected person through the bites of female sandfly. Rarely the parasite can transmit through placenta from mother to child, through sexual intercourse, as laboratory acquired and through blood transfusion. This paper reports a unique case of transfusion-transmitted fatal kala-azar in an Indian infant who acquired this infection within few days of his birth after receiving blood from his maternal uncle, who was asymptomatic at the time of blood donation but died due to severe kala-azar within three months. The baby started having fever and developed hepatosplenomegaly within one month of blood transfusion and in spite of repeated anti-leishmanial treatment with sodium antimony gluconate the child died at the age of 7 months. This paper details the clinico-pathological findings of this child and also reviews the literature on this aspect and its impact on transfusion medicine.

Animals↗
PubMed2002

Cytochrome P450 2E1 dependent catalytic activity and lipid peroxidation in rat blood lymphocytes.

To investigate the similarities in the catalytic activity of blood lymphocyte P450 2E1 in blood lymphocyte with the liver isoenzyme, NADPH dependent lipid peroxidation and activity of N-nitrosodimethyamine demethylase (NDMA-d) was studied in rat blood lymphocytes. Blood lymphocytes were found to catalyse NADPH dependent (basal) lipid peroxidation and demethylation of N-nitrosodimethylamine (NDMA). Pretreatment with ethanol or pyrazole or acetone resulted in significant increase in the NADPH dependent lipid peroxidation and the activity of NDMA-d in blood lymphocytes and liver microsomes. In vitro addition of CCl(4) to the blood lymphocytes isolated from control or ethanol pretreated rats resulted in an increase in the NADPH dependent lipid peroxidation. Significant inhibition of the basal and CCl(4) supported NADPH dependent lipid peroxidation and NDMA-d activity in blood lymphocytes isolated from control or ethanol pretreated rats by dimethyl formamide or dimethyl sulfoxide or hexane, solvents known to inhibit P450 2E1 catalysed reactions in liver and anti- P450 2E1, have indicated the role of P450 2E1 in the NADPH dependent lipid peroxidation in rat blood lymphocytes. The data indicating similarities in the NADPH dependent lipid peroxidation and NDMA-d activity in blood lymphocyte with the liver microsome have provided evidence that blood lymphocyte P450 2E1 could be used as a surrogate to monitor and predict hepatic levels of the enzyme.

Acetone↗
PubMed2002

Contribution of calcium and other dietary components to global variations in bone mineral density in young adults.

A research project on comparative international studies of osteoporosis using isotope techniques was organized by the International Atomic Energy Agency (IAEA) with the participation of 12 countries (Brazil, Canada, Chile, China, Croatia, Hungary, Philippines, Russia, Singapore, South Africa, Turkey, and the United Kingdom). Participating centers in 11 countries (all but the UK) made measurements and collected data on men and women aged 15 to 49 years. In addition to studies of bone mineral density (BMD) at the femoral neck and lumbar spine using DEXA, anthropometric, lifestyle, and nutritional data were also collected. The results of the nutritional studies are reviewed in this paper. Overall, about 8% of the observed variability in spine BMD could be attributed to nutritional factors in men and women; in men, no such relationship could be determined. No single nutritional component (not even calcium) stood out as being of particular importance across all participating centers.

Absorptiometry, Photon↗
PubMed2001

The cyclin B1 gene is actively transcribed during mitosis in HeLa cells.

In mammalian cells, the expression level of the cyclin B1 gene plays a critical role in the progression through mitosis. Here we demonstrate that the transcriptional activity of the human cyclin B1 promoter, as well as the rate of gene transcription, is high during mitosis. Indeed, the cyclin B1 promoter maintains an open chromatin configuration at the mitotic stage. Consistent with this, we show that the cyclin B1 promoter is occupied and bound to NF-Y during mitosis in vivo. Our results provide the first example of RNA polymerase II-dependent transcription during mitosis in mammalian cells.

Blotting, Northern↗
PubMed2001

Cytochrome P450 1A1 (CYP1A1) in blood lymphocytes evidence for catalytic activity and mRNA expression.

Studies initiated to characterise the catalytic activity and expression of CYP1A1 in rat blood lymphocytes revealed significant activity of 7-ethoxyresorufin-O-deethylase (EROD) in rat blood lymphocytes. Pretreatment with 3-methylcholanthrene (MC) and beta-naphthoflavone (NF) resulted in significant induction in the activity of lymphocyte EROD suggesting that like the liver enzyme, EROD activity in lymphocytes is inducible and is mediated by the MC inducible isoenzymes of P450. The increase in the activity of EROD was associated with a significant increase in the apparent Vmax and affinity of the substrate towards EROD. That this increase in the activity of EROD could be primarily due to the increase in the expression of CYP1A1 isoenzymes was demonstrated by RT-PCR and western immunoblotting studies indicating an increase in the expression of CYP1A1 in blood lymphocytes after MC pretreatment. Significant inhibition in the EROD activity of MC induced lymphocyte by anti-CYP1A1/1A2 and alpha-naphthoflavone further provided evidence that the CYP1A1/1A2 isoenzymes are involved in the activity of EROD in blood lymphocytes. The data indicating similarities in the regulation of CYP1A1 in blood lymphocytes with the liver isoenzyme suggests that factors which may affect expression of CYP1A1 in liver may also affect expression in blood lymphocytes and that blood lymphocytes could be used as a surrogates for studying hepatic expression of the xenobiotic metabolising enzymes.

Animals↗
PubMed2001

Studies of bone density, quantitative ultrasound, and vertebral fractures in relation to collagen type I alpha 1 alleles in elderly women.

Previous studies have demonstrated that an Sp1 binding site polymorphism in the collagen type I gene (COLIA1) is related to reduced bone mineral density (BMD) and osteoporotic fractures in certain populations, particularly in the elderly. We have examined the relationship among these COLIA1 Sp1 alleles, BMD, quantitative ultrasound properties of bone, and fractures in a population-based cohort of elderly women from the UK. The study group comprised 314 women aged 75 years and over who agreed to participate in a clinical study of bisphosphonate therapy in preventing bone loss at the hip. Women were enrolled regardless of the presence or absence of osteoporosis, but those with other diseases that might affect skeletal metabolism were excluded. The genotype distribution for the Sp1 polymorphism was in Hardy-Weinberg equilibrium (SS - 78%; Ss - 20%; ss - 2%) but the proportion of individuals who carried the "s" allele (22%) was significantly lower than previously observed in another study of the UK population (37.1%) (P < 0.001). There were no significant associations between COLIA1 genotypes and metacarpal cortical index, BMD of the forearm, tibial SOS, calcaneal SOS, or calcaneal BUA. While there was a trend towards lower BMD values at the hip in patients with Ss and ss genotypes, this was not statistically significant (SS = 0.721 +/- 0.14; Ss = 0.704 +/- 0.13; ss = 0.683 +/- 0.20 P = 0.6). Prevalent vertebral fractures occurred in 22% of subjects and prior fractures of the wrist, ankle, and hip were reported by 20%, but there was no significant difference in COLIA1 genotype distribution between fracture patients and controls. We conclude that COLIA1 Sp1 alleles are not significantly associated with BMD, ultrasound properties of bone, or fractures in this population-based sample of elderly women.

Absorptiometry, Photon↗
PubMed2001

Current practice regarding re-use of trauma instrumentation: results of a postal questionnaire survey.

A total of 248 Orthopaedic Units in the UK were surveyed following two newspaper articles about broken drill bits being retained in patients' bones. Questions were asked about re-use of drills, guide wires and taps, as well as about informing patients when drill bit fragments were left in situ during trauma surgery. The response rate was 79.0%. The majority of hospitals are not using new drill bits for each case nor new guide wires. In the current medicolegal climate, the fact that the majority of consultants are informing patients soon after surgery that a drill bit has fragmented in their bone is applauded.

Equipment Failure↗
PubMed2001

Preventable smoking and exercise-related hospital admissions. A model based on the NHEFS.

BACKGROUND: The NHANES I Epidemiologic Follow-Up Study (NHEFS), a longitudinal study of a representative sample of U.S. adults, makes it possible for the first time to develop a simulation model relating hospital admissions to baseline clinical risk factors for the general adult population. The model is presented here and used to project the impact on hospital admissions of changes in smoking behavior and sedentary lifestyle. METHODS: Three kinds of projections were calculated for the cohort of adults aged 45 to 74 at baseline: projections of hospital admissions in the absence of the risk factor; projections that reflect a 10-year lag between behavior change and full health benefit; and projections that reflect both lag and incomplete adherence to behavior change. For incomplete adherence we assumed that only 10% of the at-risk population changed their behavior. RESULTS: Tests of the simulation model showed that it agreed with a Cox analysis of the hospital data and accurately projected observed hospital admissions over the study period. The projections showed that eliminating smoking would reduce annual rates of all-cause hospitalization among older adults by 8.9% 20 years after baseline. Eliminating inactivity would reduce them 4.6%. Introducing a lag of 10 years between behavior modification and full benefit delayed the impact on hospitalization rates but the effect at 20 years was the same. When only 10% of the population at risk stopped smoking or became physically active, a percentage that reflects the effectiveness of current interventions, annual hospitalization rates at 20 years fell by 0.9% and 0.5%, respectively. CONCLUSIONS: Substantial reductions in hospital admissions can be achieved by interventions to prevent smoking, help smokers quit, or encourage inactive persons to become active. Improving adherence can markedly improve the impact on hospitalizations. The costs of these efforts would be rewarded not only by better health, but by lower expenditures for hospitalization.

Age Distribution↗
PubMed2001

Atypical familial Paget's disease of bone.

We report unusual clinical and radiological features of Paget's disease of bone in three family members. All three patients had satisfactory biochemical and symptomatic response to treatment with an intravenous bisphosphonate (clodronate).

Adult↗
PubMed2000

Evidence against a redshift z > 6 for the galaxy STIS123627+621755.

The identification of galaxies at extreme distances provides the most direct information about the earliest phases of galaxy formation. But at redshifts z > 5 even the most luminous galaxies appear faint; the interpretation of low signal-to-noise ratio data is difficult and misidentifications do occur. Here we report optical and near-infrared observations of the source STIS123627+621755, which was previously suggested to be at a redshift of 6.68 (ref. 1). At that redshift, and with the reported spectral energy distribution, the galaxy should be essentially invisible at wavelengths less than 9,300 A, because the intervening intergalactic medium absorbs almost all light energetic enough to ionize neutral hydrogen--that is, with wavelengths less than the redshifted Lyman limit of lambda = (1 + z) x 912A. At near-infrared wavelengths, however, the galaxy should be relatively bright. Here we report a detection of the galaxy at 6,700 A and a non-detection at a wavelength of 1.2 microm, contrary to expectations for z approximately 6.68. The data conservatively require that STIS123627+621755 has a redshift z < 6.

Journal Article↗
PubMed2000

Cell cycle-independent induction of D1 and D2 cyclin expression, but not cyclin-Cdk complex formation or Rb phosphorylation, by IFNgamma in macrophages.

During G1 to S phase transition, D-type cyclins form complexes with cyclin-dependent kinases (Cdk), which in turn phosphorylate retinoblastoma gene product (Rb) and inhibit its growth-inhibitory function, leading ultimately to cell proliferation. We report here a novel finding that D1 and D2 cyclins are induced in macrophages by antiproliferative factor gamma interferon (IFNgamma). The induction appears to be transcriptional activation of the D cyclin genes, since indirect events such as IFNgamma-induced colony-stimulating factor-1 (CSF-1) autocrine stimulation, alteration of D1 and D2 mRNA stability and lipopolysaccharide contamination in commercial IFNgamma preparations play no roles. In contrast to CSF-1, IFNgamma neither induces D1-Cdk4 complex formation and Rb hyperphosphorylation nor interferes with CSF-1-stimulated D1-Cdk4 interaction and Rb phosphorylation, while it completely blocks CSF-1-stimulated cell proliferation. This study suggests that induction of D1 and D2 cyclins is not necessarily associated with cell cycle progression, and D cyclins may have cell cycle-independent functions in response to IFNgamma.

3T3 Cells↗
PubMed2000

Metacarpal morphometry using a semi-automated technique in the assessment of osteoporosis and vertebral fracture risk.

Metacarpal morphometry represents a potentially cheap and widely available non-invasive assessment of skeletal status. In two cross-sectional studies, we compared the performance characteristics of a semiautomated technique (the Teijin Bonalyzer) with an in-house manual measurement, and with measures of skeletal strength at other sites. The metacarpal cortical index (mCI) was measured on hand radiographs of 178 osteoporotic women using both the Teijin Bonalyzer and a digitizing tablet. Measurements on the latter were consistently lower than with the Bonalyzer except for mCI (0.443+/-0.080 vs 0.364+/-0.060, p<0.001), although correlation coefficients between these two methods were highly significant (r = 0.62-0.83, p<0.001). The reproducibility errors of metacarpal bone mineral density (mBMD) were constant (1.1-1.2%) whilst those for mCI showed a marked operator-dependency (2.0-7.9%). In 379 elderly community-dwelling women, Bonalyzer mCI and mBMD showed a significant decline with age (r = -0.30 and -0.27 respectively, p<0.05). Both mCI and mBMD correlated significantly with forearm BMD (r = 0.50 and 0.57 respectively, p<0.001) and hip BMD (r = 0.48 and 0.53 respectively, p<0.001). After adjustment for age and weight, hip BMD demonstrated the best discrimination for prevalent vertebral fractures as judged by the gradient of risk for a 1 SD decrease in measurement (odds ratio (OR) 2.17, 95% CI 1.56-3.01). Similar but smaller gradients of risk were shown by Bonalyzer mCI (OR 1.32, 95% CI 1.00-1.75), mBMD (OR 1.35, 95% CI 1.02-1.78) and forearm BMD (OR 1.39, 95% CI 1.08-1.80). MCI, and in particular mBMD, may be useful assessments of bone mass and fracture risk. In our study, it is comparable to peripheral assessment of skeletal status by forearm densitometry.

Absorptiometry, Photon↗
PubMed2000

PCR monitoring for tetracycline resistance genes in subgingival plaque following site-specific periodontal therapy. A preliminary report.

BACKGROUND: The selection of antibiotic resistance genes during antibiotic therapy is a critical problem complicated by the transmission of resistance genes to previously sensitive strains via conjugative plasmids and transposons and by the transfer of resistance genes between gram-positive and gram-negative bacteria. The purpose of this investigation was to monitor the presence of selected tetracycline resistance genes in subgingival plaque during site specific tetracycline fiber therapy in 10 patients with adult periodontitis. METHOD: The polymerase chain reaction (PCR) was used in separate tests for the presence of 3 tetracycline resistance genes (tetM, tetO and tetQ) in DNA purified from subgingival plaque samples. Samples were collected at baseline, i.e., immediately prior to treatment, and at 2 weeks, and 1, 3, and 6 months post-fiber placement. The baseline and 6-month samples were also subjected to DNA hybridization tests for the presence of 8 putative periodontal pathogenic bacteria. RESULTS: PCR analysis for the tetM resistance gene showed little or no change in 5 patients and a decrease in detectability in the remaining 5 patients over the 6 months following tetracycline fiber placement. The results for tetO and tetQ were variable showing either no change in detectability from baseline through the 6-month sampling interval or a slight increase in detectability over time in 4 of the 10 patients. DNA hybridization analysis showed reductions to unmeasurable levels of the putative periodontal pathogenic bacteria in all but 2 of the 10 patients. CONCLUSIONS: These results complement earlier studies of tet resistance and demonstrate the efficacy of PCR monitoring for the appearance of specific resistance genes during and after antibiotic therapy.

Adult↗
PubMed2000

Colony-stimulating factor-1 receptor utilizes multiple signaling pathways to induce cyclin D2 expression.

Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos and delayed early genes such as D-type cyclins (D1 and D2), whose products play essential roles in the G1 to S phase transition of the cell cycle. Little is known, however, about the cytoplasmic signal transduction pathways that connect the surface CSF-1 receptor to these genes in the nucleus. We have investigated the signaling mechanism of CSF-1-induced D2 expression. Analyses of CSF-1 receptor autophosphorylation mutants show that, although certain individual mutation has a partial inhibitory effect, only multiple combined mutations completely block induction of D2 in response to CSF-1. We report that at least three parallel pathways, the Src pathway, the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and the c-myc pathway, are involved. Induction of D2 is partially inhibited in Src(-/-) bone marrow-derived macrophages and by Src inhibitor PP1 and is enhanced in v-Src-overexpressing cells. Activation of myc's transactivating activity selectively induces D2 but not D1. Blockade of c-myc expression partially blocks CSF-1-induced D2 expression. Complete inhibition of the MEK/ERK pathway causes 50% decrease of D2 expression. Finally, simultaneous inhibition of Src, MEK activation, and c-myc expression additively blocks CSF-1-induced D2 expression. This study indicates that multiple signaling pathways are involved in full induction of a single gene, and this finding may also apply broadly to other growth factor-inducible genes.

Animals↗