Biomedical subjects

H C Hsu

Publications and source records attributed to H C Hsu.

At least 73 records · Page 4Linked to original sources

PubMed2000

Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tumor necrosis factor alpha and reduces arthritis.

The major limitation of adenovirus is its association with induction of an inflammatory response and relatively short-term production of the gene therapy transgene product. Adeno-associated virus (AAV) is a 4.68-kb single-strand DNA virus that contains ITRs for viral replication and a packaging signal, and also has been engineered to contain therapeutic genes up to 5 kb in length. Transduction of recombinant AAV (rAAV) results in low inflammatory response and long-term expression. We have cloned a low-immunogenic form of human sTNFRI (sTNFRI2.6D) into AAV (rAAVsTNFRI). This vector was analyzed for its ability to transfect and neutralize the effect of TNF-alpha on primary rheumatoid arthritis synovial fibroblast (RASFs). The rAAVsTNFRI was transduced into the cells at 1.8 x 10(1), 1.8 x 10(2), and 1.8 x 10(3) viral particles per cell. There was greater than 90% neutralization of TNF-alpha at 1.8 x 10(3) viral particles/cell. There was a significant decrease in the synovial cell hyperplasia and cartilage and bone destruction in human TNF-alpha transgenic mice treated intraarticularly with rAAVsTNFRI. These results indicate that the low-immunogenic and long-term expressing vector, rAAVsTNFRI, can be used to deliver the soluble TNF-alpha in vitro and in vivo and effectively reduce the severity of arthritis.

Animals↗

PubMed2000

Expression of the c-kit protein is associated with certain subtypes of salivary gland carcinoma.

The c-Kit protein, a receptor type tyrosine kinase that plays an important role in the development of hematopoietic cells, melanocytes, and germ cells, is expressed in mastocytosis, gastrointestinal stromal cell tumors (GISTs), germ cell tumors, and several other tumors. Gain-of-function mutations in exon 11 and exon 17 have been shown as a mechanism of c-kit activation in some tumors. To study the role of c-kit in salivary gland carcinomas, we analyzed the c-kit protein expression in 79 carcinomas of major and minor salivary glands by immunohistochemistry. Although varying in intensity of staining, c-kit expression was identified very often in adenoid cystic carcinomas (20/25), lymphoepithelioma-like carcinomas (6/6) and myoepithelial carcinomas (2/2), but not in other types of salivary gland carcinoma (0/46), P<0.00001. By DNA sequencing, genetic alteration of c-kit juxtamembrane domain (exon 11) and tyrosine kinase domain (exon 17) was not found in all the three types of salivary carcinoma that had c-kit protein expression. In conclusion, c-kit protein overexpression is involved in the pathogenesis of certain types of salivary gland carcinoma, but mutation of the gene is not the mechanism of c-kit activation.

Carcinoma, Acinar Cell↗

PubMed2000

Functional link between ataxia-telangiectasia and Nijmegen breakage syndrome gene products.

Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are recessive genetic disorders with susceptibility to cancer and similar cellular phenotypes. The protein product of the gene responsible for A-T, designated ATM, is a member of a family of kinases characterized by a carboxy-terminal phosphatidylinositol 3-kinase-like domain. The NBS1 protein is specifically mutated in patients with Nijmegen breakage syndrome and forms a complex with the DNA repair proteins Rad50 and Mrel1. Here we show that phosphorylation of NBS1, induced by ionizing radiation, requires catalytically active ATM. Complexes containing ATM and NBS1 exist in vivo in both untreated cells and cells treated with ionizing radiation. We have identified two residues of NBS1, Ser 278 and Ser 343 that are phosphorylated in vitro by ATM and whose modification in vivo is essential for the cellular response to DNA damage. This response includes S-phase checkpoint activation, formation of the NBS1/Mrel1/Rad50 nuclear foci and rescue of hypersensitivity to ionizing radiation. Together, these results demonstrate a biochemical link between cell-cycle checkpoints activated by DNA damage and DNA repair in two genetic diseases with overlapping phenotypes.

Ataxia Telangiectasia↗

PubMed2000

Concomitant boost radiation therapy for inoperable non-small-cell lung cancer: preliminary report of a prospective randomized study.

PURPOSE: The radiation therapy results for patients with inoperable non-small-cell lung cancer (NSCLC) have been disappointing. Tumor dose escalation using concomitant boost technique (CBT) has been shown to improve local control in a few prospective studies. This trial was carried out to prospectively assess the radiation response and acute toxicity of CBT in comparison to the conventional treatment technique (CTT). METHODS AND MATERIALS: Ninety-seven consecutive eligible patients were entered in this prospective clinical trial between November 1994 and February 1998. Patients were randomized to receive either CBT (43 patients) or CTT (54 patients) radiation therapy. These patients either refused chemotherapy or were judged as unsuitable for chemotherapy. Patients in the CBT group received 46.8 Gy in 26 fractions using large fields that encompassed the gross and occult disease. A concomitant boost of 18.2 Gy (0.7 Gy per fraction) was delivered to the gross disease using small fields with 1.5-cm margins. The small fields were treated concurrently with the large fields and the total dose to the tumor area was 65 Gy in 26 fractions. Patients in the CTT group received 70.8 Gy in 38 fractions. The acute toxicity between each group was compared. The response rate was analyzed and compared by treatment group, gender, age, stage, histology, initial Karnofsky performance score (KPS), severity of acute toxicity, and maximum body weight loss (MBWL) during treatment course. RESULTS: The demographic parameters such as sex, age, and stage were evenly distributed in each treatment group. The majority of these patients had Stage IIIA and IIIB disease. Overall median treatment times were 39 days for the CBT group of patients and 62 days for the CTT group. No treatment-related mortality was found. There were 2 patients in the CTT group with acute RTOG Grade 3 lung toxicity, and no Grade 3 lung or esophageal toxicity was observed in CBT group. The response rates, assessed by radiographic images, were 69.8% and 48.1% for the CBT and CTT patients, respectively. Univariate and multivariate analysis revealed that patients in the CBT group, patients with better KPS, and patients with more severe acute toxicity had a higher response rate. CONCLUSION: This study demonstrates that concomitant boost radiation therapy is tolerable, and produces a superior response rate than conventional radiation therapy for patients with inoperable NSCLC. The length of treatment was reduced from 38 to 26 treatment days, almost a 30% reduction.

Adult↗

PubMed2000

Somatic mutations of beta-catenin play a crucial role in the tumorigenesis of sporadic hepatoblastoma.

Hepatoblastoma (HB) is the most common malignant hepatic tumor during early childhood. Its molecular pathogenesis is still poorly understood. Mutations of adenomatous polyposis coli (APC) gene have been identified in sporadic cases and in individuals associated with familial adenomatous polyposis syndrome. beta-catenin is a key element in the cadherin-mediated cell adhesion system and Wnt/wingless pathway, and is controlled by APC. APC affects the degradation of beta-catenin by its NH(2)-terminal phosphorylation on the serine/threonine residues of exon 3. Mutations of these phosphorylation sites are primary targets for activating mutations in several types of human cancer and lead to nuclear accumulation of beta-catenin protein. In this study, we examined nine patients with HB using immunohistochemistry and direct DNA sequencing. All nine cases showed predominant nuclear expression of beta-catenin. Eight cases (89%) showed mutations involving exon 3 of the beta-catenin gene, including five with deletions and three with missense mutations. All five deletions were in-frame deletions without frameshift. The very high frequency of mutations in the beta-catenin gene suggests that beta-catenin mutations are crucial in the tumorigenesis of HB.

Amino Acid Sequence↗

PubMed2000

Oral glutamine to alleviate radiation-induced oral mucositis: a pilot randomized trial.

PURPOSE: To evaluate the influence of oral glutamine on radiation-induced oral mucositis in the radiotherapy of head and neck cancer. METHODS AND MATERIALS: From July 1997 through June 1998, 17 patients with head and neck cancer receiving primary or adjuvant irradiation were randomized to either glutamine suspension (16 g in 240 ml normal saline) (n = 8) or placebo (normal saline) (n = 9) arm. Patients were instructed to swish the test solutions (30 ml) four times per day. All patients received half-mouth irradiation at least. Patients were treated 1.8 Gy per fraction daily, 5 days a week. We evaluated the grading of oral mucositis daily fraction at each day of treatment until 45 Gy/25 fractions. World Health Organization (WHO) step analgesic medication and body weight change were compared between the two arms. RESULTS: The duration of objective oral mucositis > or = Grade 1 (p = 0.0097), Grade 2 (p = 0.0232), and Grade 3 (p = 0.0168) was shorter in the glutamine arm. Mean maximum grade of objective oral mucositis was less severe in the glutamine arm (1.6 vs. 2.6) (p = 0.0058). Glutamine did not reduce the duration and severity of subjective oral mucositis except for duration > or = Grade 3 (p = 0.0386). In the analysis of mean maximum WHO step of analgesic medication, there was no statistical difference (p = 0.5374) between the two arms. Mean body weight change was also not significantly different (p = 0.8070). CONCLUSIONS: Oral glutamine may significantly reduce the duration and severity of objective oral mucositis during radiotherapy. It may shorten the duration of > or = Grade 3 subjective mucositis.

Administration, Oral↗

PubMed2000

Allelic loss at chromosome band 6q14 correlates with favorable prognosis in hepatocellular carcinoma.

Cytogenetic and molecular studies have frequently shown chromosome 6q deletions in non-Hodgkin lymphoma and several human cancers. There have been few studies concerning chromosome 6q deletion in hepatocellular carcinoma (HCC), and most of these studies have focused on region 6q26-27. We previously described frequent allelic loss at 6q14 in HCC. As a step toward narrowing the scope of search for tumor suppressor genes, we used a series of yeast artificial chromosome clones that map to the long arm of chromosome 6 (6q14-6q22) by fluorescence in situ hybridization (FISH) to define the minimal common region of allelic loss in 25 cases of HCC. Altogether, 12 tumors had allelic loss on 6q (48%). Eleven of the 12 tumors had polysomy of chromosome 6 with evident intratumor cytogenetic heterogeneity. The minimal common region of allelic loss lies within a 2-cM region at 6q14, flanked by D6S458 (849_d_8) and D6S275 (911_a_3). Clinicopathologic correlation between the 12 patients with allelic loss at 6q and the 13 patients without allelic loss showed no significant differences in any basic characteristics except survival. Patients with allelic loss at 6q had a much longer median survival time than those without allelic loss (50 months vs. 11 months, P = 0.0019). Only 5 of the 25 HCC patients were still alive at the time of this study, and all of them had allelic loss at 6q, which is also statistically significant (P = 0.037, alive vs. dead). The association of allelic loss at 6q with polysomy implies that this may be a progression-associated event in HCC. The correlation of allelic loss at 6q with long survival suggests a complex mechanism of tumorigenesis in HCC and is worthy of further investigation.

Adult↗

PubMed2000

Causes of venous thrombosis in fifty Chinese patients.

In a whole year from July 1997 to June 1998, a total of 50 patients with sonogram-proved venous thrombosis who called on our hematology clinic consecutively entered into the study. Their mean age was 59.1 +/- 17.5 years, range 18-83 years, and 29 were male. A series of examinations were performed in order to find out the cause of venous thrombosis. These examinations included antithrombin, protein C, protein S, plasminogen, heparin cofactor II, activated protein C ratio, factor V Leiden mutation, fibrinogen, factors VIII and XII, euglobulin lysis time, 677 C-->T mutation of methylenetetrahydrofolate reductase (MTHFR), prothrombin 20210 (PT 20210) A allele mutation, lupus anticoagulant, anticardiolipin antibody, and complete blood count. Five patients (10%) were found to have malignancy; an inferior vena cava thrombosis in one patient was due to venous compression by hydronephrosis; two patients had lupus anticoagulant; two had varicose veins of legs; two had protein C deficiency; four had protein S deficiency; two had plasminogen deficiency; two had antithrombin deficiency. No activated protein C resistance, elevated factor VIII level, factor V Leiden, PT 20210 A allele or heparin cofactor II deficiency was found in the present study. Homozygous MTHFR 677 C-->T gene mutation was found in 7 patients (14%); one of them also had a plasminogen deficiency. No possible risk factor of venous thrombosis could be found in 24 patients (48%). In conclusion, malignancy and protein S deficiency were the most frequent acquired and congenital causes of venous thrombosis in the Chinese, respectively.

Adenocarcinoma↗

PubMed2000

Tendon-Defect and muscle-unloaded models for relating a rotator cuff tear to glenohumeral stability.

Rotator cuff tear and glenohumeral instability are closely related. Any tear may disturb muscle force generation due to pain inhibition. In addition, a full-thickness tear may foster instability by removing a structural element constraining the joint. It was hypothesized that the loss of both dynamic force and static constraint with a rotator cuff tear will affect glenohumeral stability. In a tendon-defect model, dynamic and static elements of the joint were sacrificed. In a muscle-unloaded model, only the dynamic element was removed. The location and size of the defect were also investigated. The effect on instability of a small tendon defect was less than that of muscle unloading, implying that a patient with a small tear would have less instability than a patient with weak or nonfunctioning supraspinatus and infraspinatus muscles. On the other hand, with a larger tear the defect had a greater effect than muscle-unloading because sectioning of the glenohumeral and coracohumeral ligaments was included in the model. Clinically, such a defect in the front is critical for anterior stability because it might insult the important anterior capsule ligamentous complex. Orthopaedic surgeons should pay attention, therefore, to the effect of possible associated lesions of static constraints based on the size and location of the tear in addition to the dynamic stabilizer.

Aged↗

PubMed2000

High external parametrial dose can increase the probability of radiation proctitis in patients with uterine cervix cancer.

OBJECTIVE: The aim of this study was to evaluate the relationship between external parametrial dose and radiation proctitis after external irradiation and high-dose-rate intracavitary (HDR-IC) brachytherapy among patients with cervical cancer. METHODS: From May 1993 through December 1996, 191 patients with stage IB-IVA cervical cancer were managed by curative-intent radiotherapy. External irradiation to the whole pelvis (44-45 Gy/ 22-25 fractions) was delivered to all patients initially. One hundred twenty-seven patients received additional bilateral parametrial and sidewall boost (5.4-14.4 Gy/ 3-8 fractions) with 4-cm midline shielding. HDR-IC brachytherapy, 19.2-24 Gy/ 5 fractions to Point A, was given after external irradiation. Patients receiving an external dose of 44-45, 50-54, and >54 Gy were categorized as no parametrial boost (NPMB), low parametrial boost (LPMB), and high parametrial boost (HPMB) group, respectively. The actuarial proctitis rate was compared among the three groups. RESULTS: Three-year overall and Grade 2-4 proctitis rates were 30 and 15%, respectively. Overall proctitis rates were 12, 34, and 51% in the NPMB, LPMB, and HPMB groups (P < 0.0001), respectively. Grade 2-4 proctitis rates were 5, 17, and 27% in the NPMB, LPMB, and HPMB groups (P = 0.0022), respectively. In multivariate analysis of overall and Grade 2-4 radiation proctitis, external parametrial dose was the only independent prognostic factor (P = 0.0002 and 0.0030, respectively). CONCLUSION: Regardless of central shielding after 44-45 Gy whole pelvis irradiation, more patients with high external parametrial dose developed radiation proctitis. Incomplete midline shielding of the upper rectum may be the cause. Diminishing the external beam doses further may decrease rectal complications.

Adult↗

PubMed2000

Beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis.

To better understand the role of beta-catenin mutation in hepatocellular carcinoma (HCC), we correlated the gene mutation with hepatitis virus B (HBV) and hepatitis virus C (HCV) status and the clinicopathological features in 366 patients with resected primary unifocal HCC. beta-Catenin mutations were also analyzed in 55 patients with multifocal HCC (68 tumors). Of the whole series, 57 (13.1%) of 434 tumors examined had beta-catenin mutations, 34 occurred at the serine/threonine residues of the GSK-3beta region of beta-catenin. Outside the GSK-3beta phosphorylation site, codons 32 and 34 were two mutational hot spots (17 tumors). The non-HBV-related HCC that was predominantly HCV related had a higher frequency of mutation (P: < 0.00001) and more frequent mutations at codon 45 than HBV-related HCC. HBV-related HCC had a younger mean age (P: < 0.00001), and higher male-to-female ratio (P: < 0.003) and positive familial history of HCC (P: < 0.014). Among 366 unifocal HCCs selected for clinicopathological analysis, beta-catenin mutations were associated with grade I (P: = 0.005) and stage I and II HCC (P: < 0.0001), and a better 5-year survival rate (P: = 0. 00003). These findings suggest mechanisms for beta-catenin mutations differ between HBV-related and non-HBV-related HCCs, and that beta-catenin mutation is a favorable prognostic factor related to low stage. beta-Catenin mutation was associated with nuclear expression of the protein (P: < 0.00001), but we failed to detect point or large fragment deletion mutation in 39 HCCs with nuclear beta-catenin expression, presumably wild-type protein. HCCs expressing mutant nuclear beta-catenin had a better 5-year survival rate (P: < 0.007), suggesting that mutant and wild-type nuclear beta-catenin proteins are not functionally equivalent and deserve more studies for further clarification.

Base Sequence↗

PubMed2000

Multivariate analysis of pulmonary fibrosis after electron beam irradiation for postmastectomy chest wall and regional lymphatics: evidence for non-dosimetric factors.

BACKGROUND AND PURPOSE: To evaluate the factors associated with pulmonary fibrosis after postmastectomy electron beam irradiation of chest wall and regional lymphatics in patients with breast cancer. MATERIALS AND METHODS: From July 1987 through July 1994, 109 women with stage II and III breast cancer receiving modified radical mastectomies were managed by postoperative electron beam irradiation. Doses of 46 to 50.4 Gy were delivered to the chest wall covered with bolus, internal mammary nodes, supraclavicular nodes and axillary lymph nodes via 12 or 15 MeV single portal electron beam. Seventeen patients received additional 10-16 Gy surgical scar boost via 9 MeV electron beam. Comparison of pre-treatment and post-treatment chest X-ray films were used to monitor the development of pulmonary fibrosis. RESULTS: Only Grade 1 radiation-induced late pulmonary toxicity was noted in 33 patients (29%). Twenty-six patients (24%) developed pulmonary fibrosis under unbolused chest wall. Lung fibrosis under bolused chest wall was noted in 11 patients (10%). Statistical difference (P<0.01) was noted between the incidence of fibrosis in these two sites. In multivariate analysis of lung fibrosis under unbolus-covered chest wall, the independent prognostic factors are low body mass index (BMI) (P<0.01), tamoxifen taking (P=0.03), and no treatment interruption (P=0.03). No independent factor was associated with lung fibrosis under bolus-covered chest wall in multivariate analysis. CONCLUSIONS: In the analysis of pulmonary fibrosis induced by unbolused electron beam, BMI rather than body weight and body height is a strong prognostic factor. Tamoxifen and short overall time can predispose the development of lung fibrosis.

Adult↗

PubMed2000

Rapidly progressive fibrosing interstitial nephritis associated with Chinese herbal drugs.

Rapidly progressive fibrosing interstitial nephritis after a slimming regimen containing aristolochic acid has been identified as Chinese herbs nephropathy (CHNP). From 1995 to 1998, we observed 12 Chinese people from different areas of Taiwan who underwent renal biopsy for unexplained renal failure. Medical history gave no clue to the causes of impaired renal function except for the ingestion of traditional Chinese herbs. Although these patients ingested herbal drugs from various sources for different purposes, their renal biopsy samples showed amazingly similar histological findings, with extensive hypocellular interstitial fibrosis and atrophy and loss of tubules in all cases. Glomeruli were apparently intact. They also had similar clinical features, such as normal or mildly elevated blood pressure, early and severe anemia, low-grade proteinuria, glycosuria, and insignificant urinary sediments. Renal function deteriorated rapidly in most patients despite discontinuation of the herbal medicines. Seven patients underwent dialysis, and the remainder experienced slowly progressive renal failure. Bladder carcinoma was found in one patient. Morphologically and clinically, the nephropathy in our patients was similar to CHNP, reported in Belgium. Because of the complexity and unknown types of herbs used in different clinical situations, unidentified phytotoxins other than aristolochic acid might be responsible for this unique disease entity. We conclude that the relation of this nephropathy to the consumption of Chinese herbs is striking. Using uncontrolled herbal remedies carries a high risk for developing interstitial renal fibrosis and urothelial malignancy.

Adult↗

PubMed2000

Retinoic acid-induced apoptotic pathway in T-cell lymphoma: Identification of four groups of genes with differential biological functions.

Retinoic acid (RA) has been used to induce the regression of refractory T-cell lymphoma. In vitro and in vivo studies have shown that RA exerts this effect through the induction of apoptosis. This study was designed to investigate the molecular pathway of RA-induced apoptosis in T-lymphoma cell lines.RA-induced apoptosis was verified by morphology, flow cytometry, and DNA ladder analysis. Differential display method using a combination of 12 poly(A)-anchored primers and 20 arbitrary primers was adopted for gene cloning. Total RNAs were extracted from H9 cell line at 0, 6, 12, and 24 hours after All-trans RA (ATRA) treatment and the serial expression patterns of the candidate fragments were recognized. The cloned gene fragments were then analyzed and confirmed by Northern blot analysis on H9 and SR786 cell lines.ATRA-induced apoptosis of T-cell lymphoma was protein synthesis-dependent. The execution or irreversible phase of apoptosis appeared to occur at 6-12 hours of RA treatment. Among the 60,000 arbitrarily displayed bands, 25 of 250 candidate fragments were selected for further cloning and sequencing. A total of 14 clones could be matched to known genes and were categorized into four groups: A) transcription factors: prothymosin, CA150, p78 serine/threonine kinase, IL-1beta-stimulating gene, glucocorticoid receptor, MLN64/CAB1, gastrin-binding protein, and polypeptide from glioblastoma; B) chaperone: 90 kDa heat shock protein; C) ion channel: chloride channel protein 3; and D) cytoskeleton: cytovillin2/ezrin and vimentin. Another two clones of genes were of unrecognized functions. The remaining 11 clones belonged to unmatched or novel genes. The expression of these genes varied, either upregulated or downregulated, in response to ATRA treatment.RA-induced apoptosis may involve a cascade of genes that are related to transcription regulation, stress response, housekeeping, and the execution of apoptosis. The clarification of the RA-induced apoptotic pathway will help us to understand the molecular mechanism of cancer differentiation agents.

Apoptosis↗

PubMed2000

Water-soluble Hexasulfobutyl[60]fullerene inhibit low-density lipoprotein oxidation in aqueous and lipophilic phases.

Oxidative modification of low-density lipoprotein (LDL) plays a pivotal role in the pathogenesis of atherosclerosis. Increasing the resistance of LDL to oxidation may therefore mitigate, or even prevent, atherosclerosis. A new water-soluble C60 derivative, hexasulfobutyl[60]fullerene [C60 - (CH2CH2CH2CH2-SO3Na)6; FC4S], consisting of 6 sulfobutyl moieties covalently bound onto the C60 cage is a potent free radical scavenger. This study explored the antioxidative effect of sulfobutylated fullerene derivatives (FC4S) on LDL oxidation. FC4S was found to be effective in protecting LDL against oxidation induced by either Cu2+ or azo peroxyl radicals generated initially in the aqueous or lipophilic phase, respectively. Levels of the oxidative products, conjugated diene and thiobarbituric acid-reactive substances, and the relative electrophoresis mobility of the LDL were decreased. The addition of 20 microM FC4S at the early stage of oxidation increased the kinetic lag time from 69 +/- 11 to 14 +/- 10 min (P < 0.05) and decreased the propagation rate from 17.1 +/- 2.6 to 6.3 +/- 1.0 mOD/min (P < 0. 005). Persistent suppression of peroxidation reaction was observed upon further addition of FC4S after full consumption of all endogenous antioxidants during the propagation period. Intravenous injection of hypercholesterolemic rabbits with FC4S (1 mg/kg/day) efficiently decreased atheroma formation. Data substantiate the use of FC4S as an excellent hydrophilic antioxidant in protecting atheroma formation, via removing free radicals, in either aqueous or lipophilic phase.

Animals↗

PubMed2000

Effect of n-3 fatty acids on the composition and binding properties of lipoproteins in hypertriglyceridemic patients.

BACKGROUND: Treatment of hyperlipidemic patients with fish oil results in an increase in plasma LDL cholesterol despite a marked decrease in the LDL precursor, VLDL. OBJECTIVE: We studied the relation between VLDL composition and LDL concentrations. DESIGN: Fourteen hypertriglyceridemic patients were treated with encapsulated fish oil (containing 1.45 g eicosapentaenoic acid and 1. 55 g docosahexaenoic acid/d) for 4 wk. Venous blood samples were collected before and after treatment. Eleven normolipidemic subjects served as a control group. RESULTS: Fish oil effectively lowered plasma lipid and apolipoprotein (apo) E concentrations in the hypertriglyceridemic patients, whereas apo B concentrations increased. The lipid and apolipoprotein content of VLDL decreased, whereas LDL cholesterol and LDL apo B increased. Fractionation of VLDL by heparin-affinity chromatography showed that before treatment hypertriglyceridemic patients had more VLDL in the 0.05-mol NaCl/L subfraction and less in the 0.20-mol/L subfraction than did control subjects (P < 0.05), whereas the subfraction distribution pattern was normalized after fish-oil treatment. Nevertheless, plasma concentrations of the 0.05-mol NaCl/L subfraction were decreased and those of the 0.20-mol/L subfraction were increased in hypertriglyceridemic patients after fish-oil treatment (P < 0.05). Fish-oil treatment both enhanced VLDL binding and lowered LDL binding to fibroblasts. CONCLUSION: Treatment of hypertriglyceridemic patients with fish oil caused differential effects on VLDL subfractions and decreased LDL binding to fibroblast receptors, which may have contributed to the paradoxical increase in LDL-cholesterol concentrations.

Apolipoproteins B↗

PubMed2000

Congenital interstitial cell of cajal hyperplasia with neuronal intestinal dysplasia.

Interstitial cells of Cajal (ICCs) are intestinal pacemaker cells that initiate peristalsis in the stomach and intestine, and are considered to be precursors of gastrointestinal stromal tumors (GISTs). We report a 2-year-old girl who suffered from scanty stool passage since birth. On barium enema, the distal colon was rigid with narrow lumen, whereas the proximal colon was dilated and atonic. She received right hemicolectomy and ileostomy. Histopathologically, there was continuous proliferation of spindle cells located between the layers of the muscularis propria throughout the right colon. These spindle cells were positive for c-kit and CD34 but negative for myogenic or neurogenic markers, indicating they are ICCs. No germline or somatic mutation of the juxtamembrane domain of c-kit gene was detected. In addition, the changes of the submucosal plexus fulfilled the histologic criteria of neuronal intestinal dysplasia type B. To our knowledge, this is the first reported case of congenital ICC hyperplasia. Further studies of ICC development may contribute to better understanding of the pathogenesis of this congenital malformation and the tumorigenesis of GIST.

Antigens, CD34↗

PubMed2000

Water-soluble hexasulfobutyl [60] fullerene inhibits plasma lipid peroxidation by direct association with lipoproteins.

Free radicals can induce lipid peroxidation, leading to the formation of atherosclerosis. A new class of water-soluble C60 derivative, hexasulfobutyl [60] fullerene [C60-(CH2CH2CH2CH2SO3Na)6; (FC4S)], comprising six sulfobutyl functional groups covalently bound on a C60 cage, is a potent free radical scavenger. This study sought to define the effect of FC4S in protecting plasma from peroxidation. At concentrations of 10-100 microM, FC4S efficiently protected plasma against Cu2+-induced oxidation, as shown by maintenance of apoprotein B integrity and decrease in oxidative products levels, conjugated diene, and thiobarbituric acid-reactive substances. Addition of FC4S to both plasma and isolated lipoproteins, including very low density, low-density, and high-density lipoproteins, resulted in an increased mobility of the lipoprotein on agarose gel electrophoresis. This was attributed to FC4S associating with the lipoproteins because of the negative charge of the sulfonate groups after hydrolysis in the electrophoretic buffer. When lipoprotein was oxidized by 2,2-azobis (2,4-dimethyl-valeronitrile), which produces peroxyl radicals within lipoprotein, but not in the aqueous phase, the FC4S still efficiently inhibited lipoprotein oxidation. These data substantiate that FC4S acts efficiently in protecting plasma lipid from oxidation by associating with lipoprotein to scavenge free radicals in both the aqueous and lipophilic phases.

Apolipoproteins B↗