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J Dey

Publications and source records attributed to J Dey.

At least 19 recordsLinked to original sources
PubMed2005

The tau mutation in the Syrian hamster differentially reprograms the circadian clock in the SCN and peripheral tissues.

The hypothalamic suprachiasmatic nuclei (SCN), the principal circadian oscillator in mammals, are synchronized to the solar day by the light-dark cycle, and in turn, they coordinate circadian oscillations in peripheral tissues. The tau mutation in the Syrian hamster is caused by a point mutation leading to a deficiency in the ability of Casein Kinase 1epsilon to phosphorylate its targets, including circadian PER proteins. How this accelerates circadian period in neural tissues is not known, nor is its impact on peripheral circadian oscillators established. We show that this mutation has no effect on per mRNA expression nor the nuclear accumulation of PER proteins in the SCN. It does, however, accelerate the clearance of PER proteins from the nucleus to an extent sufficient to explain the shortened circadian period of behavioral rhythms. The mutation also has novel, unanticipated consequences for circadian timing in the periphery, including tissue-specific phase advances and/or reduced amplitude of circadian gene expression. The results suggest that the tau mutation accelerates a specific phase, during mid-late subjective night of the SCN circadian feedback loop, rather than cause a global compression of the entire cycle. This reprogrammed output from the clock is associated with peripheral desynchrony, which in turn could account for impaired growth and metabolic efficiency of the mutant.

Animals↗
PubMed2002

Peptidylprolyl isomerase A (PPIA) as a preferred internal control over GAPDH and beta-actin in quantitative RNA analyses.

A good internal control is critical in all quantitative analyses of gene expression. Levels of bet-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and peptidylprolyl isomerase A (PPIA) were analyzed in 78 samples (data obtained from our laboratory and from a publicly available database at http://www.ncbi.nlm.nih.gov/SAGE/). These libraries included cell lines and tissues from brain, breast, colon, kidney, ovary, pancreas, prostate, skin, and vascular origin. The level of PPIA mRNA is the most constant among the three genes. Hence, our study suggests that PPIA is a better internal control than beta-actin or GAPDH, the two most commonly used internal controls.

Actins↗
PubMed2001

Clinicopathologic analysis of invasive micropapillary differentiation in breast carcinoma.

Invasive micropapillary carcinoma (IMPCa) of breast is histologically characterized by growth of cohesive tumor cell clusters within prominent clear spaces resembling dilated angiolymphatic vessels. In this study, eighty three breast carcinomas with IMPCa differentiation were identified by review of the invasive carcinoma cases in our institution and correlated retrospectively with standard clinicopathologic parameters and survival status relative to a control series of cases (mean follow up 7 years). IMPCa growth pattern was present in 6% of all breast carcinomas; it was generally a focal component in otherwise typical invasive ductal carcinoma. It comprised more than 80% of the total neoplasm in only 10 cases (12%), 50-80% of the neoplasm in 7 cases (8%), 20-50% of the neoplasm in 22 cases (26%) and less than 20% in 44 cases (53%). The mean tumor size was 4 cm, 22% invaded skin, and 58% were poorly differentiated, but 71% were ER positive. Axillary node metastases were present in 77% of cases, were typically multiple (51% had three or more positive), and usually contained an IMPCa component (81% of the cases). There was no significant difference in node status, ER status, size, tumor grade, or peritumoral angiolymphatic invasion between tumors with predominant (more than 50%) v/s focal IMPCa components. In both groups 46% of the patients died from their disease (mean interval to death = 36m). Skin involvement and nodal status were the only parameters which predicted poor survival (P =.01). The outcome of patients with IMPCa did not differ significantly from infiltrating ductal carcinomas of similar node status. In conclusion, our results suggest that IMPCa growth pattern may be a manifestation of aggressive behavior, as shown by frequent skin invasion and extensive nodal involvement. However, clinicopathologic features and outcome of IMPCa are not strongly dependent on the relative amount of micropapillary component.

Aged↗
PubMed2000

Gleason score 7 prostate cancer: a heterogeneous entity? Correlation with pathologic parameters and disease-free survival.

OBJECTIVES: Gleason score 7, in different proportions of grades 3 and 4, is the score most frequently assigned to prostate cancer in our radical prostatectomy specimens (RPSs). We correlated the major grade component of score 7 tumors with clinicopathologic parameters and disease-free survival. METHODS: All Gleason score 7 RPSs were classified as having a major grade of 3 or 4 carcinoma. The two groups were compared according to patient age, race, serum prostate-specific antigen (PSA) level, clinical and pathologic stage, tumor volume, and biochemical recurrence. RESULTS: Of the 534 patients analyzed, 356 and 178 had major grade 3 or 4 tumors, respectively. Compared with patients with 3+4 tumors, those with 4+3 had significantly more advanced clinical and pathologic stages, larger tumor volume, higher preoperative PSA levels, and older age and a higher proportion were African American (P <0.05 for all above parameters). With a mean follow-up of 34.6 months, patients with 3+4 tumors experienced lower rates of PSA recurrence than did those with 4+3 tumors (P = 0.0021). Furthermore, for the subset of patients with organ-confined disease, multivariable analysis that included race, age, clinical stage, preoperative PSA level, tumor volume, and major grade component found only the latter to be a significant predictor of recurrence, with patients who had major grade 4 component tumors experiencing a higher incidence of PSA recurrence than those with major grade 3 tumors (P = 0.012). CONCLUSIONS: The major grade 4 component in Gleason score 7 carcinoma indicates a higher likelihood of biochemical recurrence, particularly for the increasing proportion of patients with organ-confined disease after radical prostatectomy.

Aged↗
PubMed2000

Significance of the Gleason scoring system after neoadjuvant hormonal therapy.

Neoadjuvant hormonal therapy (NHT) induces morphologic changes in prostate adenocarcinoma that result in the assignment of higher Gleason scores on average than in pretreatment biopsy specimens. This outcome has led to the recommendation that the Gleason scoring system not be applied to prostate adenocarcinoma specimens after NHT. We reviewed the radical prostatectomy specimens of 116 patients who had received NHT. Gleason scores were assigned on the post-treatment specimens by applying the usual criteria; in addition, an estimated pretreatment Gleason score was assigned on the basis of knowledge of the morphologic alterations associated with NHT. Finally, an estimate of the degree of therapy effect was assigned: little or no evidence of hormonal effect (grade 1) to marked therapy-related changes (grade 3). Both the post-treatment and the estimated pretreatment Gleason score correlated significantly with biochemical progression (P = 0.03 and P = 0.03, respectively; log-rank test). The degree of therapy effect did not correlate with progression (P = 0.46; log-rank test). This limited analysis suggests that despite the morphologic alterations induced by NHT, post-treatment Gleason score remains a significant prognostic measure. Further studies in more uniformly treated populations are required to confirm this observation.

Adenocarcinoma↗
PubMed2000

8pter-p23 deletion is associated with racial differences in prostate cancer outcome.

Deletions of chromosome sequences mapping to the short arm of chromosome 8 have been observed frequently in a variety of human cancers. A small number of studies have suggested that the terminal portion of the short arm of chromosome 8, 8pter-p23, may be deleted independently of other portions of 8p in human tumors, and that deletion of the 8pter-p23 region may be correlated with poor prognosis. The aim of the present study was to physically define the minimal region of 8pter-p23 deletion and to define the frequency and prognostic significance of 8pter-p23 loss in human prostate tumors. DNA was purified from normal and tumor tissues of 45 radical prostatectomy specimens and amplified for 15 highly polymorphic microsatellite sequences, 13 spanning 8pter-p23 and 2 proximal 8p markers. Allelic loss of 8p sequences was observed in 28 of 45 (62%) tumors examined. Of these, approximately half (12 of 28; 43%) demonstrated independent loss of the 8pter-p23 region, with several tumors defining a 5-cM minimal region of deletion spanning D8S264-D8S1824-D8S1781-D8S262-D8S1798. When serum prostate-specific antigen was used as a surrogate end point marker for survival, 8pter-p23 loss was significantly associated with reduced disease-free progression (log-rank P = 0.0426). Moreover, loss of the 8pter-p23 region was significantly associated with poor survival for American Caucasian (log-rank P = 0.0024) but not African-American (log-rank P = 0.5832) prostate cancer patients. These studies suggest that independent deletion of 8pter-p23 is differentially associated with disease recurrence and poor outcome in American Caucasian but not African-American prostate cancer patients.

Aged↗
PubMed1999

On the Nature of the Compact Star in 4U 1728-34.

The discovery of kilohertz quasi-periodic oscillations (kHz QPOs) in low-mass X-ray binaries (LMXBs) with the Rossi X-Ray Timing Explorer has stimulated extensive studies of these sources. Recently, Osherovich & Titarchuk suggested a new model for kHz QPOs and the related correlations between kHz QPOs and low-frequency features in LMXBs. Here we use their results to study the mass-radius relation for the atoll source 4U 1728-34. We find that, if this model is correct, 4U 1728-34 is possibly a strange star rather than a neutron star.

Journal Article↗
PubMed1999

Defining and measuring quality of diabetes care.

The literature on diabetes mellitus has increasingly focused on the quality of diabetes care and its measurement. Serious and widespread quality problems exist throughout American medicine. Current efforts to improve will not succeed unless we undertake a major, systematic effort to overhaul how we deliver health care services, educate and train clinicians, and assess and improve quality. This article defines the components of quality of diabetes care provision and discusses approaches to their measurement individually and globally.

Clinical Competence↗
PubMed1999

Internet use by endocrinologists.

Endocrinologists, like other physicians, are information managers. They manage both disease-specific and patient-specific information and must integrate both types of information to provide the best possible care for their patients. New technologies offer abundant new approaches to medical information management tasks. Many will focus on computer hardware and software applications; others will seek solutions from video, telecommunications, the marriage of computer and consumer electronics, and other evolving technologies popularly referred to as multimedia and virtual reality. Few innovations in history have had the potential to so profoundly change our lives as the Internet. The incredible growth of the Internet to a vast system of interconnected networks serving more than 75 million users in the United States alone largely has been driven by the growth of newsgroups and e-mail, providing a means of communication among Internet users and particularly the World Wide Web (WWW). Information on web pages can be "linked" so that users can click on a link and navigate to other information on the same page, on other pages of the same document, on other files on the same computer, or on other computers linked to the Internet anywhere in the world. Moreover, the navigation requires no knowledge of arcane, difficult-to-remember commands. Hypertext links have the great utility of allowing users to navigate through information according to their own interests and information needs, as opposed to those of an author. The WWW also allows authors to link to other sources of information, rather than having to recreate it themselves. Increasingly easy access to the WWW has dramatically reduced the barriers to publication of information, since it is much easier and much less expensive to place information on the WWW than it is to publish and distribute it in hard copy form. This ease of publication has led to an incredible proliferation of information on the WWW. Much WWW information is of value to health professionals, including endocrinologists. This chapter reviews a variety of potential uses of the Internet by endocrinologists in their clinical, research, and educator roles and provides a number of examples of each. Approaches to finding useful information on the Internet are addressed. Finally, we include some speculation about the role of the Internet in the future practice of endocrinology.

Decision Making, Computer-Assisted↗
PubMed1998

Activation of horse liver alcohol dehydrogenase upon substitution of tryptophan 314 at the dimer interface.

Horse liver alcohol dehydrogenase contains two tryptophan residues per subunit, Trp-15 on the surface of the catalytic domain and Trp-314 buried in the interface between the subunits of the dimer. We studied the contributions of the tryptophans to fluorescence and catalytic dynamics by substituting Trp-314 with a leucine residue and making two compensatory mutations that were required to obtain a stable protein, leading to the triple mutant M303F-L308I-W314L enzyme. The substitutions increased by two- to sixfold the turnover numbers for ethanol oxidation, acetaldehyde reduction, and the dissociation constants of the coenzymes. The rate of the exponential burst phase for the transient oxidation of ethanol increased slightly, but the rate of dissociation of the enzyme-NADH complex still limited turnover of ethanol, as for wild-type enzyme. The three substitutions at the dimer interface apparently activate the enzyme by allowing more rapid conformational changes that accompany coenzyme binding, probably due to movement of the loop containing residues 293 to 298. The emission spectrum of M303F-L308I-W314L enzyme, which contains Trp-15, was redshifted compared to wild-type enzyme. Time-resolved fluorescence measurements with the triple mutant show that the decay of Trp-15 is dominated by a approximately 7-ns component. In the mutant enzyme with Trp-15 substituted with phenylalanine, the decay of Trp-314 is dominated by a approximately 4-ns component. Solute quenching data for wild-type enzyme and the mutants show that only Trp-15 is exposed to iodide and acrylamide, whereas Trp-314 is inaccessible. The luminescence properties of the tryptophan residues in the mutated enzymes are consistent with conclusions from studies of the wild-type enzyme [M. R. Eftink, 1992, Adv. Biophys. Chem. 2, 81-114].

Alcohol Dehydrogenase↗
PubMed1998

Roles and microenvironments of tryptophanyl residues of spinach phosphoribulokinase.

Phosphoribulokinase is one of several Calvin cycle enzymes that are light-regulated via the ferredoxin-thioredoxin system (R. A. Wolosiuk and B. B. Buchanan, 1978, Arch. Biochem. Biophys. 189, 97-101). Substitution of the only two Trp residues of the enzyme was prompted by the following goals: to identify each tryptophanyl residue with respect to prior classifications as exposed and buried (C. A. Ghiron et al., 1988, Arch. Biochem. Biophys. 260, 267-272); to explore the possible active-site location and function of conserved Trp155, as suggested by sequence proximity to catalytic Asp160 (H. A. Charlier et al., 1994, Biochemistry 33, 9343-9350); and to determine if fluorescence of a Trp residue can serve as a gauge of conformational differences between the reduced (active) and the oxidized (inactive) forms of the enzyme. Emission spectra and acrylamide quenching data demonstrate that Trp155 is solvent exposed, while Trp241 is buried. Kinetic parameters of the W241F mutant are not significantly altered relative to those of wild-type enzyme, thereby discounting any requirement for Trp at position 241. While substitution of Trp155 with Phe or Ala has little impact on Vmax, the Km for Ru5P and ATP are increased substantially; the diminished affinity for ATP is particularly pronounced in the case of the Ala substitution. In further support of an active-site location of Trp155, its fluorescence emission is subject to quenching by nucleotides. Fluorescence quenching of reduced W241F by ATP gives a dissociation constant (Kd) of 37 microM, virtually identical with its Km of 46 microM, and provides for the first time a direct measurement of the interaction of the kinase with product ADP (Kd of 1.3 mM). Fluorescence quenching of oxidized W241F by ATP reveals a Kd of 28 mM; however, this weakened binding does not reflect an altered microenvironment of Trp155, as its steady-state emission and fluorescence lifetimes are unaffected by the oxidation state.

Amino Acid Sequence↗
PubMed1998

Enhanced separation of antidepressant drugs using a polymerized nonionic surfactant as a transient capillary coating.

The separation of seven structurally similar antidepressant drugs (amitriptyline, nortriptyline, imipramine, desipramine, protriptyline, doxepin, and nordoxepin) was achieved in under 15 min using a novel nonionic micelle polymer, poly(n-undecyl-alpha-D-glucopyranoside) (PUG) by use of capillary zone electrophoresis (CZE). Systematic studies with varying polymer concentration, pH, and percent organic modifier were conducted in order to find the optimum conditions for baseline separation of the seven tricyclic antidepressants. In addition, equations for capacity factor were used to estimate the extent of what was initially thought to be micelle analyte interaction. A series of calculations show that a modified CZE system (PUG-CZE) was the actual mode of separation. Thus, our study concluded that PUG functioned in a non-electrokinetic chromatography mode.

Antidepressive Agents↗
PubMed1997

Cognitive function in younger type II diabetes.

OBJECTIVE: To examine central nervous system involvement as a possible complication of diabetes by performing a comprehensive neuropsychological evaluation of relatively young (age < 55 years) NIDDM patients and a group of control subjects. RESEARCH DESIGN AND METHODS: A cross-sectional comparative study of 28 patients, with duration of diabetes 5-18 years (mean +/- SD +/- 3.2 years), screened for acceptable glycemic control and absence of hypoglycemia on the day of examination, compared with 28 demographically similar, nondiabetic control subjects. Neuropsychometric tests performed were Mini-Mental Status Examination (MMSE), Neurobehavioral Cognitive Status Examination (NCSE), and P300 latencies (endogenous evoked potentials). RESULTS: Seven (25.0%) patients reported history suggestive of cognitive impairment during day-to-day activities, and 17 (60.7%) had distal symmetrical polyneuropathy. Average P300 latencies were significantly delayed among the diabetic patients compared with the control subjects (349.5 +/- 28.2 vs. 312.9 +/- 19.3 ms; t = 5.68, P < 0.001). Although there was no significant difference in MMSE scores, compared with control subjects significantly more patients had impairment in NCSE tests of attention (chi 2 = 7.38, P < 0.01), repetition (chi 2 = 4.073, P < 0.05), and memory (chi 2 = 5.83, P < 0.05), while there was no significant difference in tests of comprehension, naming, construction, and calculation. Duration of diabetes, HbA1c levels, and the presence of distal symmetrical polyneuropathy among patients each did not correlate with any of the parameters of cognitive function evaluated. Higher blood glucose levels during the electrophysiological testing were associated with less delay in P300 latencies among the patients. CONCLUSIONS: Central nervous system impairment, manifesting as mild impairments in certain cognitive skills, should be recognized as a possible complication of long-standing NIDDM, even in relatively younger individuals.

Adult↗
PubMed1995

MnPcS4: a new MRI contrast enhancing agent for tumor localisation in mice.

Manganese-tetrasulfonated phthalocyanine (MnPcS4) has been evaluated as a potential contrast agent in Magnetic resonance imaging (MRI) for tumor localisation in mice. MnPcS4 showed favourable molar relaxivity, much better than Gd-DTPA and comparable to tetrasulfonated manganese complex of porphyrin (TPPS4). Tumors showed selective retention of the metal complex (dye) with the peak value reached at 24 hours following intravenous administration. Dye concentration in tumors remained consistently higher than either kidney or muscle tissue both at 1 and 24 hours and a 10-fold increase in tumor-to-muscle ratio over the control was seen at 24 hr. Normal liver tissue, however, showed higher concentration than tumor at all times during the study. A linear correlation was found between longitudinal relaxation rate (1/T1) and the corresponding concentration of MnPcS4 in various tissues. MR imaging done in animals using 1.5 T superconducting clinical imager showed a mean percent increase in signal intensity of 131.8% (SD +/- 32.86) in the tumor and a 70% increase in tumor-to-muscle ratio over the pretreatment value, at 24 hr. The results suggest that MnPcS4 is a potential tumor-selective contrast agent in MRI.

Animals↗
PubMed1992

A scanning electron microscope study of Raillietascaris varani (Baylis et Daubney, 1922) (Nematoda: Ascaridioidea).

The Raillietascaris varani (Baylis et Daubney, 1922), parasitic in the Indian monitor lizard, Varanus monitor (L.), was studied by scanning electron microscopy (SEM). A surface topography of the worm, especially the head and male tail, were described, illustrated and discussed with regard to the available data on this species, and also other species of ascaridoid nematodes. The present study confirms the previous observations from Sprent (1985), and also provides some additional information concerning the microtopography of the worm which might be useful in comparative studies on the Ascaridoidea.

Animals↗