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Biomedical subjects

H C Hsu

Publications and source records attributed to H C Hsu.

At least 19 recordsLinked to original sources

Increased acute-phase response and renal amyloidosis in aged CD2-fas-transgenic mice.

We previously demonstrated that increased Fas expression in T cells of aged CD2-fas transgenic (Fas-Tg) CD-1 mice results in an increased immune response and T cell apoptosis. Surprisingly, despite prevention of T cell immune senescence, the average life span of Fas-Tg mice is comparable with that of nontransgenic (non-Tg) mice. Histopathologic evaluation of tissue sections showed that nearly 50% of the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas no amyloid deposition was observed in aged non-Tg mice. The amyloid A deposition was observed primarily in glomeruli by using immunohistochemical stains and electron microscopy. The full-length amino acid coding sequence of serum amyloid A2 cDNA in CD-1 mice was identical to that of amyloid A amyloidosis-susceptible BALB/c mice. Although there was no significant difference in steady-state serum amyloid A level in the serum of aged non-Tg and Fas-Tg mice, challenging mice with staphylococcal enterotoxin B resulted in significantly higher serum levels of serum amyloid A on day 2 and IL-6 on days 1 and 2 and a higher magnitude of weight loss on day 7 in aged Fas-Tg mice compared with young mice. These parameters, at the indicated time points, were equivalent between young and aged non-Tg mice. Taken together, our data suggest that prevention of T cell senescence in Fas-Tg mice may be a factor in induction of an excessive acute-phase response triggered by T cell activation. The Fas-Tg mice are a novel model for understanding the immunologic mechanisms leading to secondary amyloidosis.

Acute-Phase Reaction

Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella volvacea.

A new fungal immunomodulatory protein (Fip) has been purified from the edible mushroom, Volvariella volvacea, and designated Fip-vvo. Analysis of the purified protein by SDS/PAGE followed by Coomassie Blue staining demonstrated that Fip-vvo is a single polypeptide with an apparent molecular mass of 15 kDa. Periodic acid/Schiff staining showed that this single polypeptide lacks carbohydrates. Using an in vitro bioassay measuring blast-formation stimulatory activity, Fip-vvo was shown to stimulate the maximum proliferation of human peripheral blood lymphocytes at a concentration of 5 microg/ml. Fip-vvo was capable of agglutinating rat red blood cells. Neither haemagglutination nor mitogenic activities were inhibited by mono- or dimeric sugars. In vivo, repeat administration of Fip-vvo greatly reduced the production of BSA-induced Arthus reaction in mice, whereas little effect was observed on the prevention of systemic anaphylaxis reactions. The selectively enhanced transcriptional expression of interleukin (IL)-2, IL-4, interferon-gamma, tumour necrosis factor-alpha, lymphotoxin and IL-2 receptor by Fip-vvo was also demonstrated by reverse transcriptase-PCR. This finding suggests that Fip-vvo exerts its immunomodulatory effects via cytokine regulation. In addition, the complete amino acid sequence of Fip-vvo was obtained by direct protein sequencing. This protein consists of 112 amino acid residues with a blocked N-terminal end and has a calculated molecular mass of 12667 Da not including the N-terminal blocking group. By gel filtration analysis, Fip-vvo exhibited a molecular mass of 26 kDa for the native molecules in PBS. This result indicates that native Fip-vvo is most likely a non-covalently associated homodimeric molecule.

Adjuvants, Immunologic

The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes.

The present study was to ascertain the immunomodulating and anti-tumor effects of Ganoderma (G.) lucidum. Polysaccharides (PS) from fresh fruiting bodies of G. lucidum (PS-G) were isolated and used to potentiate cytokine production by human monocytes-macrophages and T lymphocytes. Our results had shown that the levels of interleukin (IL)-1 beta, tumor necrosis factor (TNF)- alpha, and IL-6 in macrophage cultures treated with PS-G (100 micrograms/ml) were 5.1-, 9.8- and 29-fold higher, respectively, than those of untreated controls. In addition, the release of interferon (IFN)- gamma from T lymphocytes was also greatly promoted in the presence of PS-G (25-100 micrograms/ml). Furthermore, these cytokine-containing mononuclear cell-conditioned media (PSG-MNC-CM) were found to suppress the proliferation and clonogenicity of both the HL-60 and the U937 leukemic cell lines. DNA labeling and gel electrophoresis showed that treatment with PSG-MNC-CM markedly induced leukemic-cell apoptosis. Flow-cytometric analysis revealed that few (2.3 +/- 0.8%) apoptotic cells were seen in the control cultures, while PSG-MNC-CM treatment resulted in a significant increase in the apoptotic population both in the HL-60 (38.3 +/- 4.5%) and in the U937 (44.5 +/- 3.8%) cells. In addition, 40 to 45% of the treated leukemic cells were triggered to differentiate into mature monocytic cells expressing CD14 and CD68 surface antigens. However, PS-G alone had no such effects even at a higher dose of 400 micrograms/ml. Since untreated macrophages and T lymphocytes produced little or no cytokine, and normal MNC-CM did not suppress leukemic cell growth, it was suggestive that the anti-tumor activity of PSG-MNC-CM was derived from the elevated levels of cytokines. Antibody-neutralization studies further revealed that the anti-tumor cytokines in the PSG-MNC-CM were mainly of TNF- alpha and IFN- gamma, and these 2 cytokines acted synergistically on the inhibition of leukemic-cell growth.

Adjuvants, Immunologic

Concordance of positive and negative symptoms in coaffected sib-pairs with schizophrenia.

Positive and negative symptom (NGS) dimensions were examined for their concordance in 46 coaffected schizophrenic sib-pairs. Results showed that the symptom dimensions of negative symptoms (NGS), delusion-hallucination (DHS), and thought disorganization (TDS) could be formulated. Discrete genetic endowment of these three symptom dimensions was not found as shown by the low concordance in sib pair analysis (kappa = 0.20-0.30). Thirty-seven pairs (80.4%) and 21 pairs (45.7%) had liability, defined by the presence of NGS in any one member of the coaffected sib-pairs, of NGS of "any degree", and of "severe degree" in 46 sib-pairs, respectively. Both groups had high prevalence (59.1-81.0%) of positive symptoms. Another 9 (19.6%) and 25 (54.3%) pairs had no liability of NGS of "any degree" or of "severe degree" out of 46 sib-pairs, respectively. These two groups had high concordance (kappa = 0.45-1.00) of TDS or DHS between coaffected sib-pairs. Based on the results, it is hypothesized that schizophrenia, as defined by DSM-III-R, may consist of two subtypes: one has liability of NGS and a high prevalence of positive symptoms, while the other has only positive symptoms.

Delusions

Primary transplantation of allogeneic peripheral blood stem cell for severe aplastic anemia.

Primary allogeneic peripheral blood stem cell transplantation (allo-PBSCT) has not been previously described in the treatment of severe aplastic anemia (SAA). We report a patient with SAA who underwent primary allo-PBSCT with cells from her HLA-identical sibling and achieved rapid bone marrow reconstitution. The patient has been in complete remission with normal blood counts for 9 months following allo-PBSCT. This suggests that primary allo-PBSCT is a safe and effective alternative in the treatment of SAA.

Adolescent

Increased apoptosis of CD45RO- T cells with aging.

Increasing susceptibility to infectious and autoimmune phenomena have long been recognized to accompany advancing age in otherwise healthy individuals. Recently animal models of aging have suggested that age-associated immune dysfunction may correlate with defects in T cell apoptosis. We have examined activation-induced apoptosis defects in human peripheral T cells from young individuals (mean age = 31 +/- 3 years old) compared to aged individuals (mean age = 67 +/- 8 years old). Following in vitro activation of T cells with PHA and IL-2, apoptosis was measured in T cell subsets using 7-amino actinomycin D (7-AAD) staining and analysis via three colour flow cytometry. There was no significant difference in apoptosis of the total CD3+ T cell population at early and late time points. Interestingly, increased apoptosis in the CD3+ CD45RO- T cell population of older adults was observed by culture day 6. While the total number of CD3+ CD45RO- cells was not different between young (< 33 years) and old (> 65 years) individuals, 32% of these cells did not undergo apoptosis in younger individuals while only 10% of these cells avoided this fate in older individuals. These results suggest that accumulation of CD45RO+ T cells may occur in aged subjects due in part to preferential elimination of CD45RO- cells with activation. Furthermore, as new or continued immune response requires differentiation of CD45RO+ T cells to CD45RO+ T cells after activation, increased apoptosis instead of survival in aged individuals could lead to observed T cell immune deficiency.

Adult

Influence of lateral release on patellar tracking and patellofemoral contact characteristics after total knee arthroplasty.

The influence of lateral release of retinaculum on patellofemoral kinematics and contact characteristics after total knee arthroplasty was investigated in vitro. Lateral release altered the patellar tracking in patellar flexion, rotation, tilting, and translation. The contact force was decreased at high flexion angles. The contact area was slightly decreased and the contact region shifted laterally on the patellar button and medially on the femoral component at most of the flexion angles. The results suggest that the lateral release in total knee arthroplasty can change some patellar tracking and patellofemoral joint contact characteristics.

Cadaver

On confidence limits associated with Chow and Shao's joint confidence region approach for assessment of bioequivalence.

Confidence limits associated with Chow and Shao's 90% joint confidence region method (C&S CR limits) were derived to assess the bioequivalence (BE) of drug products. The C&S CR method provides three conditions that must be simultaneously satisfied to conclude BE, which is applicable only for raw scale data. The C&S CR limits method extends its applicability to both raw scale and log-transformed data. In addition, it is easy to interpret. The quantitative limits provide information, such as how much the test product deviates from the reference product in bioavailability. The data sets of peak plasma concentration (C(max)) and area under plasma concentration curve (AUC) of 13 BE studies involving 10 drugs were used to compare the performances of classic confidence interval (classic CI), C&S CR, and C&S CR limits methods. The results indicate that the same BE conclusion can be reached for C&S CR and C&S CR limits methods. The C&S CR and its limits method offered a distinctive advantage in terms of percentage passing the BE criteria by taking account of the correlation and variability of sample means. Similar BE conclusion was observed for C&S CR limits method by using raw and log-transformed data in this study.

Biological Availability

Case report: primary cystic keratinizing squamous cell carcinoma of the liver in a patient with treated nasopharyngeal carcinoma.

Primary squamous cell carcinoma of the liver is very rare; only 18 cases have been recorded. In the present report we document an additional case who had a unique history of stage III non-keratinizing nasopharyngeal carcinoma treated with a full course of radiotherapy in July 1993. Two small hypoechoic cyst-like lesions in the left hepatic lobe were identified at the same time. In July 1995 the 50-year-old patient reported to be suffering from abdominal fullness and tenderness. A large hypodense tumour was demonstrated in the left hepatic lobe by abdominal echography. The patient was diagnosed as having metastatic carcinoma and received two courses of pre-operative chemotherapy followed by left lobectomy of the liver and resection of adherent tissues on 9 August 1995. Pathological study demonstrated a larger hepatic cystic keratinizing squamous cell carcinoma, which most likely arose from a solitary hepatic cyst. Tumour seedings, probably secondary to tumour rupture, were also revealed on the omentum, peritoneum and diaphragm. However, regional lymph nodes were fee of tumour. Systemic work-up failed to demonstrate evidence of local recurrence of nasopharyngeal carcinoma, metastatic lesion or any second primary tumour site.

Antineoplastic Agents

Expression of P-glycoprotein and p53 in advanced hepatocellular carcinoma treated by single agent chemotherapy: clinical correlation.

Hepatocellular carcinoma (HCC), a chemoresistant tumour, is the most common fatal cancer in Taiwan. Hepatocellular carcinoma frequently expresses a high level of P-glycoprotein (P-gp), which is a specific phenotype of a multidrug-resistance gene, and harbours mutations of the tumour suppressor gene p53. A modulatory relationship between p53 and P-gp has been reported. In this study, we analysed the expression of P-gp in relation to chemotherapeutic response and p5353 protein expression in advanced HCC. Prechemotherapeutic tumour samples were obtained from 25 patients with HCC which had been treated with either etoposide (VP-16) or doxorubicin. P-glycoprotein and p53 in HCC were visualized by immunohistochemical staining using the monoclonal antibodies JSB-1 and DO1, respectively. We investigated the correlation of P-gp expression with chemotherapeutic responses, clinicopathological features and p53 protein expression. In our study, seven cases achieved partial remission, and the remaining 18 cases had a poor response to chemotherapy. Expression of P-gp was observed in 13 tumours (52%). Positive P-gp protein expression was significantly associated with non-responders (8% or 1/13 vs 50% or 6/12, P = 0.03). Thus, P-gp expression inversely correlated with chemotherapeutic response. Expression of p53 protein was seen in 12 cases and did not correlate with chemosensitivity or P-gp expression. In summary, P-gp expression correlates with the chemosensitivity of HCC that has been treated with VP-16 or doxorubicin and p 53 mutations do not appear to be a major determinant of P-gp expression in advanced HCC.

ATP Binding Cassette Transporter, Subfamily B, Mem

Physiological elongation of ligamentous complex surrounding the hindfoot joints: in vitro biomechanical study.

Ligaments surrounding the hindfoot joints play an important role in hindfoot stability. This in vitro study investigated anatomical and biomechanical characteristics of nine major ligamentous structures, including length and orientation at neutral position and physiological elongation with the foot in five different positions relative to the neutral position. The results showed that ligament elongation depended on the ligament length, orientation in neutral position, and movement of bones to which they were attached.

Aged

Immunohistochemical analyses of p53 protein expression in breast cancers in Taiwan: a clinicopathologic study.

Immunohistochemical analysis of the p53 protein was performed on paraffin sections of tumor tissue from 210 breast cancer patients. All patients had a follow-up period of more than 5 years. Protein expression of p53 was detected in 64 patients (30.5%). There was significant correlation between p53 protein expression and a high histologic grade (grade II vs grade I/II, 49% vs 23.6%, p = 0.0008) and high mitotic index (> or = 10/10 hpf vs < 10/10 hpf, 42.9% vs 19.6%, p = 0.0004), but not with axillary node status, stromal lymphocytic infiltration, or estrogen receptor or progesterone receptor status. We found that p53 protein expression was not a significant factor in predicting 5-year mortality.

Adult

The double-blind test of sodium hyaluronate (ARTZ) on osteoarthritis knee.

BACKGROUND: At this time, no definite treatment exists for osteoarthritis disease. Hyaluronate (ARTZ) is one of the most important components of synovial fluid. It is generally accepted that hyaluronic acid protects the articular cartilage and soft tissue surfaces from trauma during joint function. METHODS: Ninety patients with 116 knees diagnosed as early arthritis (mild to moderate) by four senior orthopaedic surgeons were selected to join this study. The trial design was applied with a double-blind model. The selected patients were randomly injected with 2.5 ml drugs (ARTZ or placebo) intra-articularly once a week for five consecutive weeks without the use of local anesthetic drugs. Evaluation results included grading of subjective and objective symptoms and daily activities. The follow-up period was up to six months after initial injection. RESULTS: According to the results of clinical evaluation and statistical analysis, SPH (ARTZ) is quite effective for osteoarthritis knees, and significantly better than the placebo. The effective peak was one week after five injections of ARTZ. The effective period could last up to three months without additional treatment. The efficacy of ARTZ on osteoarthritis knees was more prominent for relief of motion pain and improvement of knee movement. No side effects developed during a six month period. CONCLUSIONS: Based on clinical results here, SPH is a safe drug for administration as an alternative approach to treat the osteoarthritis knee.

Activities of Daily Living

Leiomyosarcoma of the left atrium: a case report.

Primary malignant cardiac tumors are uncommon, and cardiac leiomyosarcoma is extremely rare. We reported a case of left atrial (LA) leiomyosarcoma with unusual clinical manifestations. A 28-year-old female presented with unknown cause of fever, body weight loss and anemia for two months. Echocardiography and magnetic resonance image study disclosed a 5 x 3 x 3.6 cm3 lobulated mass in the LA with invasion to its posterior wall. Histologic and immuno-histochemical studies of the resected specimen revealed a picture of leiomyosarcoma. The patient improved after surgical resection and post-operative chemotherapy. The literature was reviewed with a discussion of the clinical manifestations, diagnosis and treatment strategy of this rare tumor. Diagnosis of LA leiomyosarcoma is frequently delayed to make a very poor prognosis. Postoperative chemotherapy should be considered because of highly possible incomplete resection. However, an optimal treatment regimen remains unknown.

Adult

Long-term outcome after surgery for asymptomatic small hepatocellular carcinoma.

The subjects of this study were 48 asymptomatic patients who had surgery for small hepatocellar carcinoma (HCC). There were 42 men and six women with mean (s.d.) tumour size of 3.31 (1.46) cm and age 55.0 (7.4) years. Follow-up was for a minimum of 10 years. The main concern of this study was a univariate analysis of factors that might affect long-term survival after surgery, which was 50 per cent at 5 years and 31 per cent at 10 years. A high incidence of recurrent HCC (37 of 48 patients) was observed but reoperation further prolonged life in some cases. The significant prognostic factors detected by multivariate analysis were: histological classification, functional liver reserve and histology of the resection margin. Tumour size, gross appearance of tumour, presence of liver cirrhosis, serum alpha-fetoprotein level, age or sex did not affect the prognosis.

Carcinoma, Hepatocellular

Expression in human endothelial cells of ADP-ribosylation factors, 20-kDa guanine nucleotide-binding proteins involved in the initiation of vesicular transport.

ADP-ribosylation factors (ARFs) are approximately 20-kDa, guanine nucleotide-binding proteins, initially discovered as stimulators of cholera toxin ADP-ribosyltransferase activity and subsequently shown to participate in vesicular trafficking. Five of the six mammalian ARFs have been identified in human tissues by molecular cloning. They fall into three classes (class I: ARFs 1-3; class II: ARFs 4, 5; class III: ARF 6) based on deduced amino acid sequence, size, phylogenetic analysis, and gene structure. Similar to the rab family of approximately 20 kDa guanine nucleotide-binding proteins, the ARFs appear to function in specific trafficking pathways. The presence of a specific ARF might serve as a marker for that pathway. To verify expression of ARF mRNA and protein in human umbilical vein endothelial cells, immunoreactivity using antibodies specific for each ARF class, quantitative polymerase chain reaction (PCR) using ARF-specific, internal cRNA standards containing unique restriction enzyme cleavage sites introduced by point mutations, and Northern analysis with probes specific for ARFs 1, and 3-6, were utilized. PCR and Northern analysis were in agreement in showing that amounts of mRNA for ARF 1 and ARF 4 were similar and higher than those of ARF 3 and ARF 5 which were greater than ARF 6. Primarily, Class 1 ARF proteins were detected by immunoreactivity, with the majority in the supernatant fraction. The relative expression of ARFs in endothelial cells thus differs from that in neuronal tissues where it had been found that ARF3 is the predominant species.

ADP-Ribosylation Factor 6

Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay. A clinicopathologic study and demonstration of the usefulness of a third-generation assay.

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be, further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.

Chronic Disease

Surgical resection for recurrent hepatocellular carcinoma: prognosis and analysis of risk factors.

BACKGROUND: Hepatocellular carcinoma (HCC) is common in Asian countries, and tumor recurrence is the most common cause of treatment failure after curative resection. Repeated hepatectomy is performed only for selected patients because most patients with HCC also have liver cirrhosis and poor liver function reserve. The purposes of this study were to clarify the outcome of the patients after second hepatectomy for recurrent HCC and to evaluate the prognostic factors after second hepatectomy. METHODS: We used retrospective cohort study to examine the disease-free survival, cumulative survival, and possible prognostic factors for recurrence and death in 59 patients who underwent surgical resection for recurrent HCC at the National Taiwan University Hospital from August 1986 to December 1993. Another 64 patients with unresectable recurrent HCC were used as a historical control group. The survival curves between those patients with resectable HCC and those with unresectable HCC were compared. RESULTS: After resection for recurrent HCC, gender and multiplicity (n > 3) of tumor affect recurrence rate (p = 0.046 and 0.021, respectively), whereas gender, age, and tumor invasiveness affect survival rate significantly (p = 0.024, 0.021, and 0.046, respectively). The survival rate of patients with resectable HCC was significantly better than that of those with unresectable HCC. CONCLUSIONS: For recurrent HCC surgical resection is an effective mode of treatment in selected patients. Whether surgery is better than other modes of treatment in the treatment of resectable recurrent HCC demands further investigation.

Adult