Comparison of Tuberculosis Infection Rates in a National Database of Renal Transplant Patients With Data From a Single Center in Taiwan

Successful renal transplantation (RT) improves quality of life and patient survival. Advances in immunosuppressants for RT have improved the prevention and treatment of acute rejection as well as reduced the risk of chronic graft damage, but immunodeficiency may render patients vulnerable to opportunistic infections. We conducted this study to compare the difference in tuberculosis (TB) infection rates between a single institution and a national database of RT recipients in Taiwan. There were 153 patients with TB (3.2%) among 4,835 RT recipients in the database during the period 2000–2009, with a higher prevalence of men (P = .018) and diabetes patients (P = .029). In our institution's registry, 33 patients (2.7%) developed 35 episodes of TB infection among 1,209 RT recipients, but there were no significant differences in general characteristics among different subgroups. Interestingly, the use of cyclosporine was significantly more frequent in RT recipients with TB than in those without in both the national database and in our institution. In contrast, TB infection was negatively correlated with the use of tacrolimus (TAC) and mycophenolate (MPA). RT recipients with TB infection had poor survival (P = .0013) and low graft survival (P = .0003). Taken together, analyses of the national database and the RT patients in our institution revealed that the use of long-term cyclosporine-based immunosuppressive agents was associated with a greater risk of developing post-transplantation TB compared with that of other immunosuppressive agents, but the chronicity and accumulation effect of TAC and MPA should be observed despite the negative correlation found herein. In conclusion, post-transplantation TB is a serious health threat and one of the major causes of death among RT recipients, and a high index of suspicion to ensure early diagnosis and prompt initiation of treatment for TB is crucial. The use of optimal immunosuppressive agents to minimize acute rejection, monitoring of high-risk recipients, prompt diagnosis, and appropriate treatment are required to manage TB infection in endemic areas such as Taiwan.     

Changing Pattern of Mortality in Renal Transplant Recipients: A Single-Center, 30-Year Experience

Introduction

Patient survival among kidney transplant (KTx) recipients has improved remarkably in the past decades. The most common causes of death are cardiovascular disease in the West; in Taiwan, the answer remains uncertain.

Methods

From 1983 to 2012, KTx patients who underwent transplantation and were followed at our hospital were recruited for the study. For comparison, patients were stratified according to the transplant time as group 1, 1983–1989 (the initial era); group 2, 1990–1998 (the cyclosporine era); and group 3, 1999–2012 (the modern era, in which tacrolimus and mycophenolate mofetil were available).

Results

A total of 520 KTx patients (male:female ratio of 285:235) were performed in our hospital during the study period. A progressive improvement in patient survival rates (P < .0001) was noted among the 3 groups. At a mean follow-up duration of 9.55 ± 8.20 years, 83 recipients had died. Overall, the most common cause of death was infection (44.6%), followed by cardiovascular disease (21.7%), malignancy (12.0%), and hepatic failure (10.8%). Infection was the main cause of death in groups 1 and 2 (44.1% and 52.6%, respectively) but not in Group 3 (18.2%), although this trend did not reach statistical significance. Death owing to cardiovascular diseases became the most common cause of death (27.3%) in the modern era (group 3).

Conclusion

The pattern of mortality among Taiwanese KTx patients has changed over the past 30 years. Infection is no longer the commonest cause of death.     

Portal Venous Pressure in Adult Living Donor Liver Transplantation

Objective

The relationship between portal pressure and small-for-size syndrome (SFSS) is unsettled. The purpose of this study was to evaluate the role of portal pressure in predicting SFSS.

Methods

Thirty-four patients with end-stage liver disease who received adult-to-adult living-donor liver transplantation (ALDLT) were included. Recipients were grouped based on whether they received portal flow modulation or not. The intraoperative portal vein flow volume (PVFV) and portal venous pressure (PVP) between the 2 groups were compared. The relationship of PVP to PVFV, graft weight-to-recipient weight ratio (GRWR), and graft weight-to-recipient spleen size ratio (GRSSR) were analyzed.

Results

Persistent portal hypertension was found after ALDLT. The PVP was linearly correlated with PVFV but not with GRWR or GRSSR. With the use of the following criteria, (1) PVFV >250 mL/min/100 g graft weight, (2) GRWR <0.8%, and (3) GRSSR <0.6, modulation of the portal flow was performed in 3 cases. The receiver operating characteristic analysis showed that 23 mm Hg was the cutoff point for PVP, with a sensitivity of 83% and specificity of 43%.

Conclusions

PVP is a weak parameter to use for portal flow modulation after ALDLT. It is sensitive but not specific to predict SFSS.     

Isolation and characterization of 57 novel polynucleotide microsatellites from yellow catfish (Pelteobagrus fulvidraco) genome for genetic analysis

Yellow catfish (Pelteobagrus fulvidraco) is one of the important economic freshwater fish in Eastern Asia. In recent years, the wild resources were decreased sharply due to overfishing and pollution. It is necessary to conserve the wild stocks for the sustainable use of the species. In this study, 200 microsatellite markers were isolated from yellow catfish genome using Roche 454 pyrosequencing method. Among these markers, 57 exhibited polymorphism in yellow catfish population collected from Songhua River in China. The number of alleles ranged from 2 to 13 and the number of effect alleles ranged from 1.112 to 8.980. The observed heterozygosity (H _o) and the expected heterozygosity (H _e) varied from 0.106 to 0.957 and from 0.102 to 0.898, respectively. Most loci conformed to Hardy–Weinberg equilibrium with the exclusion of five loci. These polymorphic loci will be valuable for population genetic structure and genetic conservation for the P. fulvidraco.     

New clues to identify proteins correlated with Attractin

In our previous study, the age‐dependent testis vacuolisation and sperm dysfunction were found in Attractin (Atrn)‐deficient mice, Atrn^mg‐3J, which is a null or nearly null allele. To explore the potential mechanism involved in these pathological changes, Attractin knock‐down in mouse Sertoli cells TM4 (psiAtrn‐TM4) was successfully established by stable RNA interference. The TM4 transfected by psiRNA‐hH1 (psiRNA‐TM4) was the control group, in which the expression of Atrn was not affected. The proteomic changes among the psiAtrn‐TM4, primary cultures of Sertoli cells of Atrn^mg‐3J (mu‐Sc) and control cells (psiRNA‐TM4) were compared by two‐dimensional gel electrophoresis. Fifteen differentially expressed protein spots of those cells were identified by matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry and the NCBI proteins database. Except the decreased expression of superoxide dismutase (SOD), there were several novel proteins associated with Atrn function, including downregulated ATP synthase, peroxiredoxin 2 and upregulated caspase 6, ketohexokinase, etc., in psiAtrn‐TM4 and mu‐Sc. These data suggest that these differentially expressed proteins may be associated with the function of Atrn in Sertoli cells, thus providing a new clue to interpret the mechanism of testis degeneration in Atrn mutants.     

shRNA-mediated GSTP1 gene silencing enhances androgen-independent cell line DU145 chemosensitivity

Purpose

Design short hairpin RNA (shRNA) interference sequence to silence glutathione S-transferase P1 (GSTP1) gene of androgen-independent prostate cancer cell line DU145, and then to explore its effect on sensitivity to chemotherapeutics.

Methods

Target sequence was picked up to form the shRNA. DU145 cell was divided into five groups according to the shRNA added for transfection: shRNA255, shRNA554, shRNA593, negative-shRNA and blank group. Fluorescence microscope was used to pick up the shRNA with the highest transfection ratio. Western blotting and RT-PCR were taken to pick up the shRNA with the best gene silencing result. 3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay and terminal de-oxynucleotidyl transferase-mediated dUTP nick end-labeling assay were used to detect survival ratio and apoptosis ratio of DU145 administered of fluorouracil (5-FU) or paclitaxel (PA) at different concentrations before and after shRNA transfection.

Results

Three different shRNA oligonucleotides (shRNA255; shRNA554; shRNA593) targeting the coding sequence of GSTP1 mRNA and one negative control shRNA were constructed. The transfection ratio of shRNA554 (76.2 ± 0.68 %) was higher than that of shRNA255 (63.3 ± 1.04 %) (P < 0.01) or shRNA593 (72.7 ± 0.33 %) (P < 0.01). After transfection of shRNA554, the mRNA and protein of level were the lowest, P < 0.01. The survival ratio of DU145 administered with 5-FU of different concentrations (30, 60, 120, 240 μg/ml) declined after transfection (P < 0.01). Besides, the apoptosis ratio increased after transfection (P < 0.01). Similarly the survival ratio of DU145 administered with PA of different concentrations (0.2, 2, 10, 20 μg/ml) declined (P < 0.01) and the apoptosis ratio increased (P < 0.01) after transfection.

Conclusions

The gene GSTP1 silence via shRNA transfection to androgen-independent prostate cancer cell line DU145 enhances the sensitivity to chemotherapeutics.