Pancreas Transplantation

The first successful pancreas transplantation in conjunction with a simultaneous kidney transplantation was performed in 1966 by Kelly, Lillehei and others from the University of Minnesota. In Taipei Veterans General Hospital, the first pancreas transplantation (simultaneously coupled with kidney transplantation) was successfully performed on September 19, 2003, and we were qualified to harvest and transplant pancreas graft by the Taiwan Department of Health on August 31, 2007. Currently, pancreas transplantation remains the most effective method of establishing physiological and durable normoglycemia for patients with diabetes mellitus. The main indication for pancreas transplantation is type 1 diabetes with diabetic complications such as nephropathy, retinopathy, neuropathy and cardiocerebral vasculopathy, or with frequent life-threatening hypoglycemia or hyperglycemia. Pancreas graft survival rate at 1 year was 85% for simultaneous pancreas-kidney transplantation, 78% for pancreas-after-kidney transplantation, and 76% for pancreas transplantation alone. At 3 years, pancreas graft survival rates were at least 62% in all categories

Ampullectomy versus pancreaticoduodenectomy for ampullary tumors

Abstract Background: Considerable controversy surrounds the treatment of ampullary neoplasms. This report describes the authors' experiences regarding the choice of either ampullectomy or pancreaticoduodenectomy for treatment of ampullary tumors. Methods: Demographics, statistical findings concerning diagnosis, surgical risks including morbidity and mortality, and outcomes were evaluated and compared between the ampullectomy and pancreaticoduodenectomy groups for ampullary tumors retrieved from a prospectively collected computer database of 992 periampullary tumors resected during the period from 1965 to 2013. Results: A total of 377 patients with ampullary tumors were included; 15 underwent ampullectomy and 362 underwent pancreaticoduodenectomy. The overall false-negative rate for diagnosis of ampullary malignancy was 11.2%, specificity was 50.0%, positive predictive value was 98.3%, negative predictive value was 12.2%, and the overall accuracy was 87.6% (77.5% by preoperative endoscopic biopsy and 83.9% by intraoperative frozen-section biopsy). Ampullectomy was associated with shorter postoperative stays and lower surgical morbidity. There was no statistical difference observed between the two groups regarding surgical mortality, pancreatic leakage, or gastric atonia. The tumor recurrence rate was lower after pancreaticoduodenectomy, but the difference between the groups was not significant. Overall, there was no difference in survival observed between the two groups. Conclusion: Because biopsy is not routinely reliable, pancreaticoduodenectomy is preferable to ampullectomy for an ampullary tumor of uncertain diagnosis. Ampullectomy is associated with lower surgical morbidity and should therefore remain in the armamentarium of the pancreatic surgeon when comorbidity precludes major surgery

15,16-Dihydrotanshinone I, a Compound of Salvia miltiorrhiza Bunge, Induces Apoptosis through Inducing Endoplasmic Reticular Stress in Human Prostate Carcinoma Cells

5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2α (eIF2α), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1α, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients

Sonoporation-mediated gene transfer into adult rat dorsal root ganglion cells

<p>Abstract</p> <p>Background</p> <p>Gene transfer into many cell types has been successfully used to develop alternative and adjunct approaches to conventional medical treatment. However, effective transfection of postmitotic neurons remains a challenge. The aim of this study was to develop a method for gene transfer into rat primary dorsal root ganglion neurons using sonoporation.</p> <p>Methods</p> <p>Dissociated cells from adult rat dorsal root ganglion (DRG) cells were sonicated for 1-8 s at 2.5-10 W to determine the optimal ultrasound duration and power for gene transfection and cell survival. Transfection efficiency was compared between sonoporation, liposome and lentiviral vector gene transfer techniques.</p> <p>Results</p> <p>The optimum ultrasound intensity was 5 W for 2 s and yielded an efficiency of gene transfection of 31% and a survival rate of 35%.</p> <p>Conclusions</p> <p>Sonoporation can be optimized to minimize cell death and yield a high percentage of transfected neurons and that this technique can be easily applied to primary cultures of rat dorsal root ganglion neurons.</p

Timosaponin AIII Suppresses Hepatocyte Growth Factor-Induced Invasive Activity through Sustained ERK Activation in Breast Cancer MDA-MB-231 Cells

Background. The aim of this study was to investigate the mechanisms by which Timosaponin AIII (TAIII) is able to inhibit HGF-induced invasion activity in the triple negative breast cancer cell line MDA-MB-231. Methods. After pretreatment with different concentrations (10−6~10−8 M) of TAIII, the cells were treated with hepatocyte growth factor (HGF, 15 ng/mL). At different time intervals after coincubation, various parameters, including the expression of c-Met, ERK, COX2, and MMP-9, which were assessed by Western blotting or by real-time PCR, were analyzed. In addition, invasive activity was also monitored. Results. HGF was found to induce c-MET activation and ERK activation, together with increased COX2 protein expression; these changes were followed by a subsequent increase in invasive activity. TAIII was found to suppress HGF-induced invasive activity and COX2 gene expression in a concentration-dependent manner (10−6~10−8 M) in parallel with increases in the phosphoforms of c-Met and ERK after TAIII treatment. The mechanisms by which TAIII suppresses HGF-induced invasive activity were demonstrated to include sustained cytoplasmic and nuclear ERK activation; these led to a suppression of nuclear ATF2 activation, which was followed by downregulation of COX2 and MMP-9 transcription. Conclusion. TAIII suppresses HGF-induced invasive activity in MDA-MB-231 cells via sustained ERK activation

Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin

AbstractPhosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI3K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P3 and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI3K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P3 production and iNOS expression in LPS-activated macrophages. Inhibition of PI3K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI3K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-κB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI3K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway

SARS Exposure and Emergency Department Workers

Of 193 emergency department workers exposed to severe acute respiratory syndrome (SARS), 9 (4.7%) were infected. Pneumonia developed in six workers, and assays showed anti-SARS immunoglobulin (Ig) M and IgG. The other three workers were IgM-positive and had lower IgG titers; in two, mild illness developed, and one remained asymptomatic

Ciprofloxacin-resistant Salmonella enterica Typhimurium and Choleraesuis from Pigs to Humans, Taiwan

We evaluated the disk susceptibility data of 671 nontyphoid Salmonella isolates collected from different parts of Taiwan from March 2001 to August 2001 and 1,261 nontyphoid Salmonella isolates from the National Taiwan University Hospital from 1996 to 2001. Overall, ciprofloxacn resistance was found in 2.7% (18/671) of all nontyphoid Salmonella isolates, in 1.4% (5/347) of Salmonella enterica serotype Typhimurium and in 7.5% (8/107) in S. enterica serotype Choleraesuis nationwide. MICs of six newer fluoroquinolones were determined for the following isolates: 37 isolates of ciprofloxacin-resistant (human) S. enterica Typhimurium (N = 26) and Choleraesuis (N = 11), 10 isolates of ciprofloxacin-susceptible (MIC <1 μg/mL) (human) isolates of these two serotypes, and 15 swine isolates from S. enterica Choleraesuis (N = 13) and Typhmurium (N = 2) with reduced susceptibility to ciprofloxacin (MIC >0.12 μg/mL). Sequence analysis of the gryA, gyrB, parC, parE, and acrR genes, ciprofloxacin accumulation; and genotypes generated by pulsed-field gel electrophoresis with three restriction enzymes (SpeI, XbaI, and BlnI) were performed. All 26 S. enterica Typhimurium isolates from humans and pigs belonged to genotype I. For S. enterica Choleraesuis isolates, 91% (10/11) of human isolates and 54% (7/13) of swine isolates belonged to genotype B. These two genotypes isolates from humans all exhibited a high-level of resistance to ciprofloxacin (MIC 16–64 μg/mL). They had two-base substitutions in the gyrA gene at codons 83 (Ser83Phe) and 87 (Asp87Gly or Asp87Asn) and in the parC gene at codon 80 (Ser80Arg, Ser80Ile, or Ser84Lys). Our investigation documented that not only did these two S. enterica isolates have a high prevalence of ciprofloxacin resistance nationwide but also that some closely related ciprofloxacin-resistant strains are disseminated from pigs to humans

Secretome-Based Identification of ULBP2 as a Novel Serum Marker for Pancreatic Cancer Detection

BACKGROUND: To discover novel markers for improving the efficacy of pancreatic cancer (PC) diagnosis, the secretome of two PC cell lines (BxPC-3 and MIA PaCa-2) was profiled. UL16 binding protein 2 (ULBP2), one of the proteins identified in the PC cell secretome, was selected for evaluation as a biomarker for PC detection because its mRNA level was also found to be significantly elevated in PC tissues. METHODS: ULBP2 expression in PC tissues from 67 patients was studied by immunohistochemistry. ULBP2 serum levels in 154 PC patients and 142 healthy controls were measured by bead-based immunoassay, and the efficacy of serum ULBP2 for PC detection was compared with the widely used serological PC marker carbohydrate antigen 19-9 (CA 19-9). RESULTS: Immunohistochemical analyses revealed an elevated expression of ULPB2 in PC tissues compared with adjacent non-cancerous tissues. Meanwhile, the serum levels of ULBP2 among all PC patients (n = 154) and in early-stage cancer patients were significantly higher than those in healthy controls (p<0.0001). The combination of ULBP2 and CA 19-9 outperformed each marker alone in distinguishing PC patients from healthy individuals. Importantly, an analysis of the area under receiver operating characteristic curves showed that ULBP2 was superior to CA 19-9 in discriminating patients with early-stage PC from healthy controls. CONCLUSIONS: Collectively, our results indicate that ULBP2 may represent a novel and useful serum biomarker for pancreatic cancer primary screening