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Articles by S Jain
Total Records ( 7 ) for S Jain
  P. A Sample , C. A Girkin , L. M Zangwill , S Jain , L Racette , L. M Becerra , R. N Weinreb , F. A Medeiros , M. R Wilson , J De Leon Ortega , C Tello , C Bowd , J. M Liebmann and for the ADAGES Study Group
 

Objective  To identify factors accounting for differences in glaucoma onset and rate of progression between individuals of African descent and European descent.

Design  A prospective, multicenter observational cohort study of 1221 participants of African descent and European descent with no glaucoma (normal), suspected glaucoma, and glaucoma. Six hundred eighty-six patient participants in the African Descent and Glaucoma Evaluation Study will be followed up longitudinally. Four hundred thirty-six participants of European descent from the Diagnostic Innovations in Glaucoma Study (DIGS) were also included. Baseline demographics, visual function (standard automated perimetry, short-wavelength automated perimetry, frequency doubling technology perimetry), optic nerve structure (retina tomography, optical coherence tomography), clinical status, and risk factors were measured.

Results  Individuals of African descent had (1) thinner corneas (P < .001) across all diagnostic groups, (2) a higher percentage of reported diabetes mellitus (P < .001) and high blood pressure (P < .001) and a lower percentage of reported heart disease (P = .001), and (3) worse pattern standard deviation for standard automated perimetry fields overall (P = .001) and within normal limits (P = .01) than individuals of European descent. No differences were present for mean intraocular pressure (P = .79).

Conclusions  Significant baseline differences were found in a number of clinical findings between persons of African descent compared with European descent. Longitudinal data from the African Descent and Glaucoma Evaluation Study will be important for determining which baseline features are important and predictive for accurate diagnosis and follow-up in this high-risk group.

Trial Registration  clinicaltrials.gov Identifier: NCT00221923.

  C. A Girkin , P. A Sample , J. M Liebmann , S Jain , C Bowd , L. M Becerra , F. A Medeiros , L Racette , K. A Dirkes , R. N Weinreb , L. M Zangwill and for the ADAGES Group
 

Objective  To define differences in optic disc, retinal nerve fiber layer, and macular structure between healthy participants of African (AD) and European descent (ED) using quantitative imaging techniques in the African Descent and Glaucoma Evaluation Study (ADAGES).

Methods  Reliable images were obtained using stereoscopic photography, confocal scanning laser ophthalmoscopy (Heidelberg retina tomography [HRT]), and optical coherence tomography (OCT) for 648 healthy subjects in ADAGES. Findings were compared and adjusted for age, optic disc area, and reference plane height where appropriate.

Results  The AD participants had significantly greater optic disc area on HRT (2.06 mm2; P < .001) and OCT (2.47 mm2; P < .001) and a deeper HRT cup depth than the ED group (P < .001). Retinal nerve fiber layer thickness was greater in the AD group except within the temporal region, where it was significantly thinner. Central macular thickness and volume were less in the AD group.

Conclusions  Most of the variations in optic nerve morphologic characteristics between the AD and ED groups are due to differences in disc area. However, differences remain in HRT cup depth, OCT macular thickness and volume, and OCT retinal nerve fiber layer thickness independent of these variables. These differences should be considered in the determination of disease status.

Trial Registration  clinicaltrials.gov Identifier: NCT00221923

  L Racette , J. M Liebmann , C. A Girkin , L. M Zangwill , S Jain , L. M Becerra , F. A Medeiros , C Bowd , R. N Weinreb , C Boden , P. A Sample and for the ADAGES Group
 

Objective  To investigate differences in visual function between the healthy eyes of people of African (AD) and European descent (ED).

Methods  Visual function was assessed in 393 AD and 367 ED participants selected from the African Descent and Glaucoma Evaluation Study and the Diagnostic Innovations in Glaucoma Study. Participants had normal appearance of the optic disc and intraocular pressure of less than 22 mm Hg. Each participant had 2 reliable 24-2 standard automated perimetry tests, and most had short-wavelength automated perimetry and frequency-doubling technology tests. The generalized estimating equation was used to adjust for intereye correlations. Results were adjusted for age, vertical cup-disc ratio, disc size, central corneal thickness, and presence of high blood pressure.

Results  The AD participants were younger (mean [SD] age, 46.2 [13.2] years) than the ED participants (age, 49.5 [16.6] years) (P = .003). The AD participants had worse mean deviation and pattern standard deviation and more points triggered as abnormal on the total and pattern deviation plots compared with ED participants on all tests (P < .05). A larger percentage of AD participants had confirmed abnormal glaucoma hemifield test results on standard automated perimetry only.

Conclusions  People of AD have significantly worse performance than people of ED on all tests of visual function. Additional research using longitudinal data is needed to determine the cause of these small but significant ancestry differences in visual function.

Trial Registration  clinicaltrials.gov Identifier: NCT00221923

  C. M Seager , A. M Puzio Kuter , T Patel , S Jain , C Cordon Cardo , J Mc Kiernan and C. Abate Shen
 

Early-stage bladder cancer occurs as two distinct forms: namely, low-grade superficial disease and high-grade carcinoma in situ (CIS), which is the major precursor of muscle-invasive bladder cancer. Although the low-grade form is readily treatable, few, if any, effective treatments are currently available for preventing progression of nonmuscle-invasive CIS to invasive bladder cancer. Based on our previous findings that the mammalian target of Rapamycin (mTOR) signaling pathway is activated in muscle-invasive bladder cancer, but not superficial disease, we reasoned that suppression of this pathway might block cancer progression. To test this idea, we performed in vivo preclinical studies using a genetically engineered mouse model that we now show recapitulates progression from nonmuscle-invasive CIS to muscle-invasive bladder tumors. We find that delivery of Rapamycin, an mTOR inhibitor, subsequent to the occurrence of CIS effectively prevents progression to invasive bladder cancer. Furthermore, we show that intravesical delivery of Rapamycin directly into the bladder lumen is highly effective for suppressing bladder tumorigenesis. Thus, our findings show the potential therapeutic benefit of inhibiting mTOR signaling for treatment of patients at high risk of developing invasive bladder cancer. More broadly, our findings support a more widespread use of intravesical delivery of therapeutic agents for treatment of high-risk bladder cancer patients, and provide a mouse model for effective preclinical testing of potential novel agents.

  S Chatterjee , A Pillai , S Jain , A Cohen and V. Patel
 

Background

There is little evidence of the feasibility, acceptability and impact of services for the care of people with psychotic disorders in low- and middle-income countries.

Aims

To describe the scaling up and impact of a community-based rehabilitation programme for people with psychotic disorders in a very-low-resource setting.

Methods

Longitudinal study of people with psychotic disorders who had been ill for an average of 8 years in a rural Indian community. All individuals received a community-based intervention package comprising psychotropic medications, psychoeducation, adherence management, psychosocial rehabilitation and support for livelihoods. The primary outcome was change in disability scores.

Results

The cohort consisted of 256 people with psychotic disorders (schizophrenia, bipolar affective disorder and other psychosis) of whom 236 people completed the end-point assessments (92%), with a median follow-up of 46 months. There were significant reductions (P<0.05) in the levels of disability for the cohort, the vast majority (83.5%) of whom engaged with the programme. On multivariate analyses, lower baseline disability scores, family engagement with the programme, medication adherence and being a member of a self-help group were independent determinants of good outcomes. Lack of formal education, a diagnosis of schizophrenia and dropping out of the programme were independent determinants of poor outcomes.

Conclusions

Community-based rehabilitation is a feasible and acceptable intervention with a beneficial impact on disability for the majority of people with psychotic disorders in low-resource settings. The impact on disability is influenced by a combination of clinical, programme and social determinants.

  R Manjithaya , S Jain , J. C Farre and S. Subramani
 

The S. cerevisiae Slt2p MAPK cascade picks out peroxisomes for autophagy-mediated degradation (pexophagy) but is not involved in turnover of other cellular components.

  L Jones , G Wei , S Sevcikova , V Phan , S Jain , A Shieh , J. C. Y Wong , M Li , J Dubansky , M. L Maunakea , R Ochoa , G Zhu , T. R Tennant , K. M Shannon , S. W Lowe , M. M Le Beau and S. C. Kogan
 

Gain of chromosome 8 is the most common chromosomal gain in human acute myeloid leukemia (AML). It has been hypothesized that gain of the MYC protooncogene is of central importance in trisomy 8, but the experimental data to support this are limited and controversial. In a mouse model of promyelocytic leukemia in which the MRP8 promoter drives expression of the PML-RARA fusion gene in myeloid cells, a Myc allele is gained in approximately two-thirds of cases as a result of trisomy for mouse chromosome 15. We used this model to test the idea that MYC underlies acquisition of trisomy in AML. We used a retroviral vector to drive expression of wild-type, hypermorphic, or hypomorphic MYC in bone marrow that expressed the PML-RARA transgene. MYC retroviruses cooperated in myeloid leukemogenesis and suppressed gain of chromosome 15. When the PML-RARA transgene was expressed in a Myc haploinsufficient background, we observed selection for increased copies of the wild-type Myc allele concomitant with leukemic transformation. In addition, we found that human myeloid leukemias with trisomy 8 have increased MYC. These data show that gain of MYC can contribute to the pathogenic effect of the most common trisomy of human AML.

 
 
 
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