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H C Chen

Publications and source records attributed to H C Chen.

At least 91 records · Page 5Linked to original sources
PubMed2000

Molecular basis for differing antineurogenic effects of GATA-1a and GATA-1b in Xenopus.

The erythroid transcription factor GATA-1 in Xenopus has been cloned as a pair of presumably duplicated genes designated as xGATA-1a and xGATA-1b. Although both xGATA-1a and xGATA-1b are able to stimulate erythropoiesis, only xGATA-1b is capable of inhibiting neurogenesis in Xenopus embryos. Chimeras of these two genes were constructed by permuting coding and untranslated regions (UTR) on both ends of these two xGATA-1, and their neurogenesis-inhibitory effects were studied. These results reveal that (1) sequence variations between the coding regions alone do not account for the neurogenesis effect; (2) 3' UTR of xGATA-1a causes the loss of the neurogenesis inhibition of xGATA-1b; (3) 3' UTR of xGATA-1b is essential to inhibit neurogenesis. In addition, the presence of either UTR does not affect the stability of the mRNA in vitro. These observations suggest the influence of 3' UTR in xGATA-1 on the inhibition of neurogenesis.

3' Untranslated Regions↗
PubMed2000

Activation of the AT1 angiotensin receptor is dependent on adjacent apolar residues in the carboxyl terminus of the third cytoplasmic loop.

The C-terminal region of the third intracellular loop of the AT(1) angiotensin receptor (AT(1)-R) is an important determinant of G protein coupling. The roles of individual residues in agonist-induced activation of G(q/11)-dependent phosphoinositide hydrolysis were determined by mutational analysis of the amino acids in this region. Functional studies on mutant receptors transiently expressed in COS-7 cells showed that alanine substitutions of the amino acids in positions 232-240 of the third loop had no major effect on signal generation. However, deletion mutations that removed Ile(238) or affected its position relative to transmembrane helix VI significantly impaired angiotensin II-induced inositol phosphate responses. Substitution of Ile(238) with an acidic residue abolished the ability of the receptor to mediate inositol phosphate production, whereas its replacement with basic or polar residues reduced the amplitude of inositol phosphate responses. Substitutions of Phe(239) with polar residues had relatively minor effects on inositol phosphate signal generation, but its replacement by aspartic acid reduced, and by positively charged residues (Lys, Arg) significantly increased, angiotensin II-induced inositol phosphate responses. The internalization kinetics of the Ile(238) and Phe(239) mutant receptors were impaired in parallel with the reduction in their signaling responses. These findings have identified Ile(238) and Phe(239) as the critical residues in the C-terminal region of the third intracellular loop of the AT(1)-R for receptor activation. They also suggest that an apolar amino acid corresponding to Ile(238) of the AT(1)-R is a general requirement for activation of other G protein-coupled receptors by their agonist ligands.

Angiotensin II↗
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

Involvement of focal adhesion kinase in hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells.

Focal adhesion kinase (FAK) has been implicated to play a critical role in integrin-mediated control of cell behavior. However, it is unclear whether FAK also participates in the regulation of growth factor-elicited cellular functions. In this study, we have demonstrated that although overexpression of FAK in Madin-Dardy canine kidney cells did not alter their growth property or ability to form tubules within collagen gel upon hepatocyte growth factor (HGF) stimulation, it apparently enhanced HGF-induced cell scattering. This enhancement was largely because of an increase in the third phase (i.e. cell migration) of cell scattering rather than the first two phases (i.e. cell spreading and cell-cell dissociation). Conversely, the expression of FAK-related nonkinase significantly ( approximately 60%) inhibited HGF-induced cell migration. Moreover, we have found that the effect of FAK on promoting HGF-induced cell motility was greatly dependent on cell-matrix interactions. We showed that HGF treatment selectively increased the expression of integrins alpha(2) and, to a lesser extent, alpha(3) in Madin-Dardy canine kidney cells and that a monoclonal antibody against integrin alpha(2) efficiently blocked HGF-enhanced cell migration on collagen. In our efforts to determine the mechanism by which FAK promotes HGF-induced cell migration, we found that FAK mutants deficient in phosphatidylinositol 3-kinase or p130(Cas) binding failed to promote HGF-induced cell migration. Interestingly, cells expressing a FAK mutant defective in Grb2 binding exhibited a rate of migration approximately 50% lower than that of cells expressing wild type FAK in response to HGF stimulation. Taken together, our results suggest a link between HGF-increased integrin expression, FAK activation, and enhanced cell motility and implicate a role for FAK in the facilitation of growth factor-induced cell motility.

Adaptor Proteins, Signal Transducing↗
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

Free flaps for reconstruction of the lower back and sacral area.

Free flap reconstruction of the lower back and sacrum is complicated by a paucity of recipient vessels and difficulties in postoperative care. From 1983 to 1997, six patients with intractable wounds of the lower back and sacral area were treated with free flaps. The flaps used were latissimus dorsi (three), combined latissimus dorsi and serratus anterior (one), and filleted leg tissue (two). The recipient vessels were the deep femoral vessels, the perforator vessels of the deep femoral system, the inferior epigastric vessels, and the superior gluteal and inferior gluteal vessels. The patients were observed in the intensive care unit for 1 week and kept in prone position for 4 weeks. All flaps survived and wounds healed primarily. For large or multiple defects of the lower back and sacrum, free tissue transfer is effective in achieving primary healing, particularly when local flaps are inadequate or have failed.

Adult↗
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

Neuronal and endothelial nitric oxide synthase expression in outer medulla of streptozotocin-induced diabetic rat kidney.

AIMS/HYPOTHESIS: Several investigations have shown that the renal medulla has a greater capacity to generate nitric oxide than the renal cortex. To further evaluate the changes of nitric oxide synthesis in the kidney, particularly in the outer medulla, in disorders involving fluid and electrolyte imbalances, we sought to determine renal nitric oxide synthase expression in the diabetic rats. METHODS: We determined renal nitric oxide synthase mRNA and urinary nitrite/nitrate excretion in 12 normal and 12 streptozotocin-induced diabetic rats by reverse transcription-polymerase chain reaction with Southern blot hybridization and with Griess reaction, respectively. Nitric oxide synthase immunoreactivity was detected by immunohistochemistry in four normal and four diabetic rats. RESULTS: Neuronal and endothelial nitric oxide synthase mRNA were 3.5-fold and 1.8-fold increased in the outer medulla of 12 diabetic rats with no difference found in the cortex and inner medulla when compared with 12 normal rats. Urinary nitrite/nitrate excretion was significantly increased from the first week after diabetic induction. In normal rats, immunohistochemical studies showed positive neuronal and endothelial nitric oxide synthase immunostaining in almost all segments of renal tubules. Diabetic rats had the greatest enhancement of immunostaining for neuronal and endothelial nitric oxide synthase in the proximal straight tubule and medullary thick ascending limb. CONCLUSION/INTERPRETATION: Our results indicate that increases in neuronal and endothelial nitric oxide synthase synthesis in the kidney, particularly in the outer medulla, possibly play an important part in the adaptation of renal function to hyperglycaemia and hyperosmolality in diabetes.

Animals↗
PubMed2000

Defective DNA repair genes in a primary culture of human renal cell carcinoma.

PURPOSE: Genomic stability is maintained by error-free DNA replication, repair, and recombination. To determine if repair genes contribute to genomic instability, we used a newly established cell line RCC-AJR (from clear-cell renal cell carcinoma) to examine hMSH2 (a mismatch-repair gene) and the gene encoding DNA beta polymerase (polbeta; a known contributor to base-excision repair). METHODS: Coding sequences of hMSH2 and polbeta were amplified by the polymerase chain reaction (PCR) using RNA from RCC-AJR cells and matched normal kidney (NK) cells from the same patient. Nucleotide sequences of the PCR products were determined by the dideoxy-DNA method and direct sequencing. Expressions of repair genes were assayed by Western blotting. Microsatellite stability in RCC-AJR cells was assayed by alteration in (CA)n repeats. RESULTS: In the RCC-AJR cells, we detected (a) a deletion of 1476 bp encoding 492 amino acids of hMSH2 cDNA, (b) an 87-bp deletion in the polbeta coding sequence, (c) truncated forms of hMSH2 and polbeta proteins, and (d) microsatellite instability. CONCLUSIONS: This study provides evidence of alterations in hMSH2 and polbeta in the homogeneous cell population of an RCC-AJR tumor culture. The data indicate that repair genes may help preserve genomic stability in this cell line. We believe that this new primary RCC-AJR cell line will prove a useful model for investigating the cascade of genetic events in renal cells that leads to renal carcinogenesis.

Carcinoma, Renal Cell↗
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

Dermatofibrosarcoma protuberans: treatment results of 35 cases.

BACKGROUND AND PURPOSE: This study evaluates the treatment results of patients with dermatofibrosarcoma protuberans. PATIENTS AND METHODS: Between August 1987 and July 1998, 35 consecutive patients with pathologically proved dermatofibrosarcoma protuberans received surgery with or without radiation therapy. Their treatment results were analyzed retrospectively. RESULTS: The patient ages ranged from 5 to 67 years (median 37 years). There were 24 males and 11 females. The anatomic sites of tumor were: trunk in 21, extremity in eight, and head and neck region in six. The maximal dimension of tumor ranged from 1.5 to 25 cm. Surgery techniques included local excision and wide excision with or without graft or flap. Adjuvant radiation therapy was given to 11 patients, with a dose ranging from 46 to 68 Gy (one pre-operative, ten post-operative). At a median follow-up of 50 months (range 11-131 months), there were 11 patients (nine patients without radiation therapy) who developed local failure. Salvage therapy (excision with or without radiation therapy) was given to all of them, and ten achieved disease control. Some patients had treatment-related moderate cosmetic or functional problems. CONCLUSIONS: Dermatofibrosarcoma protuberans is a malignancy of a high cure rate, and adjuvant radiation therapy can reliably decrease the local recurrence rate and prevent mutilation and functional deficit caused by repeated surgery.

Adolescent↗
PubMed2000

Fatal outcome after ingestion of star fruit (Averrhoa carambola) in uremic patients.

Clinical outcome of dialysis patients after eating star fruit (Averrhoa carambola) varies, but it may be fatal. In the past 10 years, 20 such patients were treated in our hospital when they developed clinical symptoms after eating the fruit or drinking star fruit juice. Their initial presentations included sudden-onset limb numbness, muscle weakness, intractable hiccups, consciousness disturbance of various degrees, and seizure. No other major events that might be responsible for these symptoms could be identified. Eight patients died, including one patient with a serum creatinine level of 6.4 mg/dL who had not yet begun dialysis. The clinical manifestations of the survivors were similar to those who died except for consciousness disturbance and seizure. Death occurred within 5 days despite emergent hemodialysis and intensive medical care. The survivors' symptoms usually became less severe after supportive treatment, and these patients subsequently recovered without obvious sequelae. The purpose of this article is to report that patients with renal failure who ingest star fruit may develop neurological symptoms and also run the risk for death in severe cases. Mortality may also occur in patients with chronic renal failure not yet undergoing dialysis.

Adult↗
PubMed2000

DGAT and triglyceride synthesis: a new target for obesity treatment?

Because triglycerides are considered essential for survival and their synthesis has been thought to occur through a single mechanism, inhibiting triglyceride synthesis has been largely unexplored as a possible target for obesity treatment. However, recent studies indicate that mice lacking acyl CoA:diacylglycerol acyltransferase (DGAT), a key enzyme in triglyceride synthesis, are viable and resistant to diet-induced obesity. Unexpectedly, this resistance is caused by a mechanism involving increased energy expenditure. These findings suggest that inhibiting specific components of triglyceride synthesis, such as DGAT, is feasible and may represent a novel approach to treating obesity.

Acyltransferases↗
PubMed2000

Cytotoxic constituents of Polyalthia longifolia var. pendula.

A new halimane diterpene, 3beta,5beta, 16alpha-trihydroxyhalima-13(14)-en-15,16-olide (1), and a new oxoprotoberberine alkaloid, (-)-8-oxopolyalthiaine (2), along with 20 known compounds, were isolated from a methanolic extract of Polyalthia longifolia var. pendula. The structures of compounds 1 and 2 were established by spectroscopic analysis. Several of these compounds were evaluated for cytotoxicity toward a small panel of human cell lines.

Alkaloids↗
PubMed2000

Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat.

Triglycerides (or triacylglycerols) represent the major form of stored energy in eukaryotes. Triglyceride synthesis has been assumed to occur primarily through acyl CoA:diacylglycerol transferase (Dgat), a microsomal enzyme that catalyses the final and only committed step in the glycerol phosphate pathway. Therefore, Dgat has been considered necessary for adipose tissue formation and essential for survival. Here we show that Dgat-deficient (Dgat-/-) mice are viable and can still synthesize triglycerides. Moreover, these mice are lean and resistant to diet-induced obesity. The obesity resistance involves increased energy expenditure and increased activity. Dgat deficiency also alters triglyceride metabolism in other tissues, including the mammary gland, where lactation is defective in Dgat-/- females. Our findings indicate that multiple mechanisms exist for triglyceride synthesis and suggest that the selective inhibition of Dgat-mediated triglyceride synthesis may be useful for treating obesity.

Absorption↗
PubMed2000

Late diagnosis of Kawasaki disease is associated with haptoglobin phenotype.

BACKGROUND: Kawasaki disease (KD) is an acute febrile illness characterized by multiple clinical and biochemical features of inflammation and the most common complications of coronary artery abnormality (CAA). Haptoglobin (Hp) is an acute-phase protein whose phenotype is known to be involved in coronary artery diseases. In this paper, we report the investigation of the association of Hp phenotype with the formation of CAA in KD. PATIENTS AND METHODS: Forty-seven consecutive patients with clinically diagnosed KD were admitted. Sera were taken before therapy of intravenous immunoglobulins (IVIG) plus aspirin, and levels of serum proteins were measured by a rate immunonephelometer. The echocardiographic criteria for coronary artery abnormality were evaluated during acute or subacute stages. Hp phenotyping was performed by Western immunoblotting. RESULTS: Duration of fever at diagnosis of KD was significantly different between patients with Hp 2-2 (6.4 +/- 1.2 days, n = 25) and with Hp1 allele (Hp 2-1 plus Hp 1-1; 8.8 +/- 3.5 days, n = 22). In contrast, serum levels of Hp between KD patients with Hp2-2 and with Hp1 allele (297 +/- 121 mg dL-1 vs. 330 +/- 101 mg dL-1, respectively) was not significantly different. On the other hand, no patients with Hp 2-2 (0/25) were recognized as having KD in subacute stage. However, 5 out of 20 patients with Hp 2-1 were recognized in subacute stage, and their incidence of CAA was 80.0% (4/5). CONCLUSIONS: Patients with Hp 2-1 have patterns of delayed or incomplete presentation of clinical symptoms. Therefore, the late diagnosis of KD is associated with haptoglobin phenotype.

Acute Disease↗
PubMed2000

Phosphorylation of HMG-I by protein kinase C attenuates its binding affinity to the promoter regions of protein kinase C gamma and neurogranin/RC3 genes.

A 20-kDa DNA-binding protein that binds the AT-rich sequences within the promoters of the brain-specific protein kinase C (PKC) gamma and neurogranin/RC3 genes has been characterized as chromosomal nonhistone high-mobility-group protein (HMG)-I. This protein is a substrate of PKC alpha, beta, gamma, and delta but is poorly phosphorylated by PKC epsilon and zeta. Two major (Ser44 and Ser64) and four minor phosphorylation sites have been identified. The extents of phosphorylation of Ser44 and Ser64 were 1:1, whereas those of the four minor sites all together were <30% of the major one. These PKC phosphorylation sites are distinct from those phosphorylated by cdc2 kinase, which phosphorylates Thr53 and Thr78. Phosphorylation of HMG-I by PKC resulted in a reduction of DNA-binding affinity by 28-fold as compared with 12-fold caused by the phosphorylation with cdc2 kinase. HMG-I could be additively phosphorylated by cdc2 kinase and PKC, and the resulting doubly phosphorylated protein exhibited a >100-fold reduction in binding affinity. The two cdc2 kinase phosphorylation sites of HMG-I are adjacent to the N terminus of two of the three predicted DNA-binding domains. In comparison, one of the major PKC phosphorylation sites, Ser64, is adjacent to the C terminus of the second DNA-binding domain, whereas Ser44 is located within the spanning region between the first and second DNA-binding domains. The current results suggest that phosphorylation of the mammalian HMG-I by PKC alone or in combination with cdc2 kinase provides an effective mechanism for the regulation of HMG-I function.

Animals↗