T Mondala

Publications of T Mondala

• Clinical and plasma proteomic markers correlating with chronic kidney disease after liver transplantation.

  Authors: J Levitsky, D R Salomon, M Abecassis, P Langfelder, S Horvath, J Friedewald, E Wang, S M Kurian, T Mondala, S Gil, R McDade, K Ballard, L Gallon

  American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 07/2011; 11(9):1972-8.

  Chronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristicsChronic kidney disease (CKD) occurs frequently after liver transplantation (LT) and is associated with significant morbidity and mortality. Thus, there is a pressing need to identify characteristics and biomarkers diagnostic of CKD to enable early diagnosis allowing preemptive interventions, as well as mechanistic insights into the progression from kidney injury to irreversible kidney failure. We analyzed 342 patients who had baseline glomerular filteration rate (GFR) >60 at the time of LT and are now >3 years post-LT. Risk factors for post-LT CKD were compared between three different groups defined by current GFR: >90 (n = 40), 60-90 (n = 146) and <60 (n = 156) mL/min. Age, cyclosporine use and pre-LT GFR were independently associated with new onset CKD. A subset (n = 64) without viral/immune disease or graft dysfunction underwent multianalyte plasma proteomic evaluations for correlation with CKD. Plasma proteomic analysis of two independent cohorts, test (n = 22) and validation (n = 42), identified 10 proteins highly associated with new onset CKD. In conclusion, we have identified clinical characteristics and a unique plasma proteomic signature correlating with new onset CKD after LT. These preliminary results are currently being validated in a prospective, multicenter study to determine if this signature precedes the onset of CKD and resolves with early interventions aimed at preserving kidney function.

• Analysis of result variability from high-density oligonucleotide arrays comparing same-species and cross-species hybridizations.

  Authors: J D Chismar, T Mondala, H S Fox, E Roberts, D Langford, E Masliah, D R Salomon, S R Head

  BioTechniques. 10/2002; 33(3):516-8, 520, 522 passim.

  There exists a significant limitation in the variety of organismsfor which microarrays have been developed because of a lack of genomic sequence data. A near-term solution to this limitation is toThere exists a significant limitation in the variety of organismsfor which microarrays have been developed because of a lack of genomic sequence data. A near-term solution to this limitation is to use microarrays designed for one species to analyze RNA samples from closely related species. The assumption is that conservation of gene sequences between species will be sufficient to generate a reasonable amount of good-quality data. While there have been relatively few published reports describing the use of microarrays for cross-species hybridizations, this technique is potentially a powerful tool for understanding genomics in model organisms such as nonhuman primates. Here we describe the analysis and comparison of hybridization characteristics and data variability from a set of cross-species (rhesus macaque) and same-species (human) hybridization experiments using human high-density Affymetrix oligonucleotide arrays. The data reveal that a large fraction of probe sets are effective at transcript detection in the cross-species hybridization, validating the application of cross-species hybridizations for nonhuman primate genomics research.

• Prednisone withdrawal followed by interferon alpha for treatment of chronic hepatitis C infection: results of a randomized controlled trial.

  Authors: J G McHutchison, R Ponnudurai, D L Bylund, A Anguiano, P J Pockros, T Mondala, L B Wilkes

  Journal of clinical gastroenterology. 03/2001; 32(2):133-7.

  Immunosuppressive therapy increases levels of hepatitis C virus (HCV) RNA, and when combined with interferon, corticosteroids have been reported to variably improve or have no effect on sustainedImmunosuppressive therapy increases levels of hepatitis C virus (HCV) RNA, and when combined with interferon, corticosteroids have been reported to variably improve or have no effect on sustained response rates. We conducted a randomized double-blind placebo-controlled trial in 39 patients with biopsy-proven chronic HCV infection and elevated alanine aminotransferase levels. Patients received either 6 weeks of a tapering dose of prednisone (60 ng, 40 mg, and 20 mg in 2-week intervals) or an identical placebo. All patients then received recombinant interferon alpha-2b, 3 million units three times a week for 24 weeks. Patients were then followed for a further 24 weeks. At the end of the study there was no significant difference in the sustained biochemical response rates between the two groups (4/20 vs. 3/19, p value was not significant). Prednisone-treated patients had a significant increase in HCV RNA from baseline during steroid treatment (400 +/- 60% increase vs. -280 +/- 140% decrease; p = 0.005). Two prednisone-treated patients were withdrawn from the study secondary to serious complications related to therapy. Prednisone priming before interferon alpha therapy in patients with chronic HCV infection does not improve the sustained response rate. This therapy was associated with an increase in viral burden and significant morbidity.

• Fluctuations in viral load (HCV RNA) are relatively insignificant in untreated patients with chronic HCV infection.

  Authors: T T Nguyen, A Sedghi-Vaziri, L B Wilkes, T Mondala, P J Pockros, K L Lindsay, J G McHutchison

  Journal of viral hepatitis. 04/1996; 3(2):75-8.

  A recently available assay to quantify serum viral load in hepatitis C virus (HCV) infection has been used to evaluate the effects of anti-viral therapies. However, variability in HCV RNA levels inA recently available assay to quantify serum viral load in hepatitis C virus (HCV) infection has been used to evaluate the effects of anti-viral therapies. However, variability in HCV RNA levels in untreated patients with HCV infection has not yet been established. We therefore prospectively measured the biological fluctuations of HCV RNA in sera from untreated patients with chronic HCV infection. Sera were collected from seven patients at 8 am and 4 pm on the same day to assess the effect of diurnal variation, daily for 5 days in a further 10 patients, biweekly for 6 weeks in nine patients and monthly for 3 months in 11 patients. All patients had biopsy-proven chronic liver disease with elevated alanine aminotransferase (ALT) values and had not received anti-viral treatment. HCV RNA was measured blinded, in duplicate, using the quantitative branched (bDNA) amplification assay (Quantiplex HCV RNA, Chiron Co. Emeryville, CA) 36 of the 37 patients studied had measurable HCV RNA throughout the study. There was no significant correlation between HCV RNA levels and ALT values or histological activity. HCV RNA levels did not appear to vary significantly within any of the groups studied and there did not appear to be a change associated with diurnal variation. All individual patients demonstrated less than a threefold fluctuation in HCV RNA throughout the study period. Hence HCV RNA levels remain relatively stable in untreated individuals with chronic HCV infection. Changes of a magnitude of threefold (0.5 log) or greater in HCV RNA levels were not observed in untreated patients.