Lung transplantation in Sauropus androgynus consumption patients in Taiwan.
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Biomedical subjects
Publications and source records attributed to H Hsu.
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Dense deposit disease (DDD) is a less common form of membranoproliferative glomerulonephritis (MPGN). The disease occurs predominantly in children and young adults and the prognosis is variable. DDD varies considerably in incidence among different populations and has not been reported in Chinese. Herein we reported 2 cases of DDD in young Chinese girls in Taiwan. Although 1 case (case 2) had mild hypertension, both patients had asymptomatic proteinuria and ran a benign course of 8 and 14 years, respectively. The histological features of case 1 resembled membranous glomerulonephritis (MGN) on hematoxylin-eosin stain, but revealed DDD on periodic acid Schiff and chromotrope-2R silver methenamine stains. Whereas case 2 showed focal MPGN on light microscopy, she had a fine granular immunofluorescence pattern resembling MGN. Characteristic intramembranous dense deposits were demonstrated by electron microscopy in the basement membranes of the glomeruli, Bowman's capsules and the renal tubules. Both patients were followed closely, and had stable normal renal function 1 year after renal biopsy.
Depleted uranium (DU) is a dense heavy metal used primarily in military applications. Although the health effects of occupational uranium exposure are well known, limited data exist regarding the long-term health effects of internalized DU in humans. We established an in vitro cellular model to study DU exposure. Microdosimetric assessment, determined using a Monte Carlo computer simulation based on measured intracellular and extracellular uranium levels, showed that few (0.0014%) cell nuclei were hit by alpha particles. We report the ability of DU-uranyl chloride to transform immortalized human osteoblastic cells (HOS) to the tumorigenic phenotype. DU-uranyl chloride-transformants are characterized by anchorage-independent growth, tumor formation in nude mice, expression of high levels of the k-ras oncogene, reduced production of the Rb tumor-suppressor protein, and elevated levels of sister chromatid exchanges per cell. DU-uranyl chloride treatment resulted in a 9.6 (+/- 2.8)-fold increase in transformation frequency compared to untreated cells. In comparison, nickel sulfate resulted in a 7.1 (+/- 2.1)-fold increase in transformation frequency. This is the first report showing that a DU compound caused human cell transformation to the neoplastic phenotype. Although additional studies are needed to determine if protracted DU exposure produces tumors in vivo, the implication from these in vitro results is that the risk of cancer induction from internalized DU exposure may be comparable to other biologically reactive and carcinogenic heavy-metal compounds (e.g., nickel).
Members of tumor necrosis factor receptor (TNFR) family signal largely through interactions with death domain proteins and TRAF proteins. Here we report the identification of a novel TNFR family member ATAR. Human and mouse ATAR contain 283 and 276 amino acids, respectively, making them the shortest known members of the TNFR superfamily. The receptor is expressed mainly in spleen, thymus, bone marrow, lung, and small intestine. The intracellular domains of human and mouse ATAR share only 25% identity, yet both interact with TRAF5 and TRAF2. This TRAF interaction domain resides at the C-terminal 20 amino acids. Like most other TRAF-interacting receptors, overexpression of ATAR activates the transcription factor NF-kappaB. Co-expression of ATAR with TRAF5, but not TRAF2, results in synergistic activation of NF-kappaB, suggesting potentially different roles for TRAF2 and TRAF5 in post-receptor signaling.
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PURPOSE: By using a murine hepatic metastatic model, we tried to investigate the possible influence of gas insufflation in colon cancer cells spreading from the portal system to the liver. METHODS: After transducing the human placental ALP gene into murine colon cancer cell line CT26, we successfully selected a clone of CT26/DAP that would yield a specific color following histochemical staining. Fifty mice were assigned into two groups, receiving either an intrasplenic injection of 10(6) CT26/DAP cells alone or the cells followed by intra-abdominal helium insufflation with the pressure of 15 cm H2O for ten minutes. Five mice in each group were used to observe their survival and the other mice were killed at four different time periods: 10 minutes, 24 hours, 48 hours, and 72 hours following cell injection. The livers and spleens were removed for histochemical staining. By counting the numbers of specific dark reddish spots of CT26/DAP cells, we could estimate the number of tumor cells on the hepatic surface. RESULTS: At the very beginning following tumor cell injection, we found a significantly greater number of tumor cells on the hepatic surface in mice with gas insufflation (6354 +/- 1072 vs. 2133 +/- 223, respectively; P = 0.012). But the difference of these two groups became smaller and smaller as time went by. The number of tumor cells on the hepatic surface would reach the lowest level at postoperative 48 hours, and the tumor foci then began to grow both in size and number. The above patterns of dynamic change in tumor cell distribution were similar in mice both with and without gas insufflation. Average survival was slightly shorter in mice with gas insufflation, but the difference was not statistically significant. CONCLUSION: Pneumoperitoneum caused by gas insufflation may increase tumor cell spread from the portal system to the liver at the very beginning stage; however, there was no significant difference in long-term survival between mice with and without gas insufflation in this murine animal model.
The hypermetabolic inflammatory state that occurs after major trauma has been extensively studied at the whole body level, however, there is only limited information on metabolic changes in individual tissues. In this study, the effect of thermal injury on metabolic function of uninjured hind limb muscle of rabbits was measured noninvasively by positron emission tomography (PET). Rabbits were subjected to full thickness burn on 25% of their body surface area. Two to three weeks after injury, PET and arterial blood sampling was performed during inhalation of 15O2, C15O2 and 11CO and after injection of 18FDG. The tissue and blood data were analyzed by standard kinetic models for blood flow, oxygen extraction fraction (OEF), oxygen utilization and glucose metabolism. A total of seven injured and five sham animals were studied. Total body oxygen consumption was measured by indirect calorimetry and plasma concentrations of glucose, insulin and IGF-1 were measured with standard assays. Compared to sham rabbits, blood flow to muscle of injured animals was unchanged. However, OEF, oxygen utilization and glucose metabolism were significantly reduced (p<0.01) in uninjured muscle of burned rabbits. These data demonstrate that thermal injury is associated with alterations in muscle metabolism, which are not related to change in blood flow.
5-Fluorouracil in combination with leucovorin has been shown to be active in therapeutic trials of metastatic colorectal carcinoma. In this study, we administered these drugs to 72 patients with metastatic colorectal carcinoma. Thirty-six of them without previous exposure to 5-fluorouracil were treated with weekly bolus injections of 5-fluorouracil (425 mg/m2) and leucovorin (25 mg/m2) supplemented with oral levamisole. Another 36 patients with or without prior 5-fluorouracil treatment received 5-fluorouracil 3,000 mg/m2 and leucovorin 300 mg/m2 in a 48-hour continuous infusion every two weeks. Clinical efficacy and toxicity were assessed by WHO criteria. Variables were tested for relations to response and survival by univariate and multivariate analysis. The response rate was 19.4% in weekly bolus arm and 13.9% in biweekly high-dose infusion arm (P = 0.527). Median survivals in the two arms were 18.4 months (weekly) and 21 months (biweekly) respectively (P = 0.708). Gastrointestinal side effects including nausea, vomiting, diarrhea and mucositia were the major toxicities of these regimens. By multivariate analysis, the only factor to influence response rate was the site of metastases (P = 0.009). The only factor to affect survival was performance status of the patient (P = 0.0001). We concluded that the two 5-fluorouracil based regimens are well-tolerated and shown to have a response rate comparable with previous reports of similar regimens in patients with metastatic colorectal cancer. Only liver metastases seemed to have a better response to therapy. Performance status is the most important prognostic factor in patients with metastatic colorectal cancer.
BACKGROUND: Enterovesical fistula is a relatively uncommon complication of pelvic malignancies, diverticulitis of the colon, postoperative irradiation or trauma. Early diagnosis of enterovesical fistula is difficult and its management, complicated. The main purpose of this study is to investigate the most appropriate diagnostic method and to discuss the choice among different surgical managements. METHODS: From 1986 to 1995, 30 patients with enterovesical fistula were diagnosed and treated at Veterans General Hospital-Taipei. The records were reviewed retrospectively with regard to symptoms, primary disease process, diagnostic studies, management, complications, mortality and follow-up. RESULTS: Recurrent urinary tract infection (UTI) accounted for 73% and was the most common presenting symptom. Fecaluria (43%) and urine per rectum (40%) were another two common presenting symptoms. The major cause of these cases was malignancy (36%), followed by postoperative radiotherapy (17%) and iatrogenic injury (17%). Most of these cases were diagnosed by cystography (90%), barium enema (75%) or cystoscopy (69%). The rectum (52%) was the most common site involved, followed by the sigmoid colon (39%). The surgical management was individualized for each patient according to the general condition and the disease process. CONCLUSIONS: By combining the results of cystography, barium enema and cystoscopy, diagnosis of enterovesical fistula can be established in almost all cases. Single-stage operation for enterovesical fistula should be limited to those patients in good nutritional state and without severe inflammation, radiation injury, intestinal obstruction, other major medical problem, advanced malignancy or old age.
Through its type 1 receptor (TNFR1), the cytokine TNF elicits an unusually wide range of biological responses, including inflammation, tumor necrosis, cell proliferation, differentiation, and apoptosis. We investigated how TNFR1 activates different effector functions; the protein kinase JNK, transcription factor NF-kappaB, and apoptosis. We found that the three responses are mediated through separate pathways. Recruitment of the signal transducer FADD to the TNFR1 complex mediates apoptosis but not NF-kappaB or JNK activation. Two other signal transducers, RIP and TRAF2, mediate both JNK and NF-kappaB activation. These two responses, however, diverge downstream to TRAF2. Most importantly, JNK activation is not involved in induction of apoptosis, while activation of NF-kappaB protects against TNF-induced apoptosis.
Positron emission tomography (PET) with L-[methyl-11C]methionine was explored as an in vivo, noninvasive, quantitative method for measuring the protein synthesis rate (PSR) in paraspinal and hind limb muscles of anesthetized dogs. Approximately 25 mCi (1 Ci = 37 GBq) of L-[methyl-11C]methionine was injected intravenously, and serial images and arterial blood samples were acquired over 90 min. Data analysis was performed by fitting tissue- and metabolite-corrected arterial blood time-activity curves to a three-compartment model and assuming insignificant transamination and transmethylation in this tissue. PSR was calculated from fitted parameter values and plasma methionine concentrations. PSRs measured by PET were compared with arterio-venous (A-V) difference measurements across the hind limb during primed constant infusion (5-6 h) of L-[1-13C, methyl-2H3]methionine. Results of PET measurements demonstrated similar PSRs for paraspinal and hind limb muscles: 0.172 +/- 0.062 vs. 0.208 +/- 0.048 nmol-1.min-1.(g of muscle)-1 (P = not significant). PSR determined by the stable isotope technique was 0.27 +/- 0.050 nmol-1.min-1.(g of leg tissue)-1 (P < 0.07 from PET) and indicated that the contribution of transmethylation to total hind limb methionine utilization was approximately 10%. High levels of L-[methyl-11C]methionine utilization by bone marrow were observed. We conclude that muscle PSR can be measured in vivo by PET and that this approach offers promise for application in human metabolic studies.
Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through signaling cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1-associated signal transducer that is involved in activating both pathways. Here we show that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively. A TRAF2 mutant lacking its N-terminal RING finger domain is a dominant-negative inhibitor of TNF-mediated NF-kappa B activation, but does not affect TNF-induced apoptosis. Conversely, a FADD mutant lacking its N-terminal 79 amino acids is a dominant-negative inhibitor of TNF-induced apoptosis, but does not inhibit NF-kappa B activation. Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.
Idiopathic Parkinson's disease (PD) is characterized by loss of dopaminergic terminals in the basal ganglia. The cocaine analog, CFT (WIN 35,428), has been shown to bind selectively to the pre-synaptic dopamine transporters and thus represents an important probe for monitoring disease progression. In this study, we evaluated [11C] labeled CFT as a PET ligand for the quantitative in vivo assay of dopamine transporter density in three normal rhesus monkeys (Macaca mulatta). One of the animals was studied after treatment with the neurotoxin, MPTP. Simulation studies demonstrated that a three injection protocol is necessary for quantitation of dopamine transporter density. The protocol consists of an initial high specific activity injection, a low specific activity "displacement dose" at 30 min, and a final high specific activity injection at approximately 90 min. Dynamic PET imaging and arterial blood sampling were started immediately before the first injection and continued for 2 h. Blood data were corrected for [11C] labeled CFT metabolites. Compartmental models describing the dynamics of labeled and the unlabeled ligand explicitly were fitted to the PET and metabolite corrected blood data. Prior to MPTP treatment, modeling of the striatal data required a saturable receptor term and yielded mean estimates of: B'max = 113 pmol/g and KD = 33 nm (n = 3). These values for B'max are in reasonable agreement with published values for [3H] CFT binding in vitro. After multiple treatments with MPTP (0.6 mg/kg x 3), B'max in one of the animals was reduced from 122 to 10.2 pmol/g. KD was relatively unaffected by MPTP treatment. These data provide additional basis for the use of [11C] CFT in monitoring the progression of Parkinson's disease and other conditions that are associated with the loss of dopaminergic nerve terminals.
The death domain of tumor necrosis factor (TNF) receptor-1 (TNFR1) triggers distinct signaling pathways leading to apoptosis and NF-kappa B activation through its interaction with the death domain protein TRADD. Here, we show that TRADD interacts strongly with RIP, another death domain protein that was shown previously to associate with Fas antigen. We also show that RIP is a serine-threonine kinase that is recruited by TRADD to TNFR1 in a TNF-dependent process. Overexpression of the intact RIP protein induces both NF-kappa B activation and apoptosis. However, expression of the death domain of RIP Induces apoptosis, but potently inhibits NF-kappa B activation by TNF. These results suggest that distinct domains of RIP participate in the TNF signaling cascades leading to apoptosis and NF-kappa B activation.
The phenomenon of anticipation has received considerable interest recently, especially among researchers investigating the genetics of psychiatric disorders. Anticipation can involve an earlier age at onset, greater severity, and/or a higher number of affected individuals in successive generations within a family. There is some controversy concerning detection of age-at-onset anticipation, due to problems of sampling bias, which may account for the phenomenon by preferentially sampling either lateronset parents or earlier-onset children. One source of bias that has not been explicitly investigated is differential age at interview between parent and child, such that parents have passed through more of the risk period than their offspring. We conducted a computer simulation study of affected parent-child pairs to determine whether, for realistic age-at-onset and age-at-interview distributions, this source of bias is a serious one. Our results show that the timing of diagnostic assessment can strongly affect the ascertainment of parent-child pairs, to produce a severely biased sample exhibiting apparent anticipation. Under realistic assumptions, an investigator may face a greatly increased risk of false positives (i.e. detecting anticipation when none exists). For example, a nominal 5% significance level may correspond to true p values as high as 50% or even approaching 100%. We conclude with an application to existing data on panic disorder.
BACKGROUND: Leiomyosarcoma of the rectum is a rare disease without well-documented report on its management and prognosis in Taiwan. To evaluate the effectiveness and prognosis of different treatments for rectal leiomyosarcoma, we reviewed a series of 12 patients with rectal leiomyosarcoma treated at our hospital. METHODS: This study is a retrospective review of 12 rectal leiomyosarcomas treated at VGH-Taipei from 1976 to 1995, with emphasis on symptoms, therapeutic procedures and prognosis. RESULTS: The majority of tumors occurred in men (n = 10) and the average age at presentation was 54.4 years. Bloody stool and perianal pain were the two most common symptoms. Nine tumors were found in the lower rectum, within 4 cm above the dentate line. Five patients received abdominoperineal resection, four received wide local excision, and three had diversion colostomy. The effect of adjuvant therapy, either chemo- or radiotherapy, was poor. The overall one-year and five-year survival rates were 83% and 46%, respectively. Liver was the principal metastatic site. The local recurrence rate was much higher in patients receiving wide local excision than in those receiving abdominoperineal resection (100% vs. 20%). CONCLUSIONS: Abdominoperineal resection is an appropriate choice of treatment for patients with operable rectal leiomyosarcoma due to its lower local recurrence rate. Wide local excision could be considered when the lesion is less than 2 cm in diameter or when patients are not suitable for radical surgery. The effect of adjuvant therapy, either radiotherapy or chemotherapy, is poor for rectal leiomyosarcoma.
Hirschsprung's disease rarely occurs in adult. If it occurs, the symptoms and signs are usually milder than those in children and manifest in form of chronic or intermittent constipation. Definite surgical intervention could be performed with good results. We reported a 36-year-old male adult with Hirschsprung's disease who manifested as obstructive colitis. The clinical course presented as abdominal fullness and pain, and colonoscopy revealed ulcerations and pseudopolyps formation in the sigmoid colon and rectum. Ganglion was absent in transanal rectal biopsy. Soave's procedure with protective ileostomy was done. Patient's bowel movements turned normal after closure of ileostomy three months later. The literature was also reviewed.
Many diverse activities of tumor necrosis factor (TNF) are signaled through TNF receptor 1 (TNFR1). We have identified a novel 34 kDa protein, designated TRADD, that specifically interacts with an intracellular domain of TNFR1 known to be essential for mediating programmed cell death. Overexpression of TRADD leads to two major TNF-induced responses, apoptosis and activation of NF-kappa B. The C-terminal 118 amino acids of TRADD are sufficient to trigger both of these activities and likewise sufficient for interaction with the death domain of TNFR1. TRADD-mediated cell death can be suppressed by the crmA gene, which encodes a specific inhibitor of the interleukin-1 beta-converting enzyme. However, NF-kappa B activation by TRADD is not inhibited by crmA expression, demonstrating that the signaling pathways for TNF-induced cell death and NF-kappa B activation are distinct.