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Biomedical subjects

H T Chen

Publications and source records attributed to H T Chen.

At least 19 recordsLinked to original sources
PubMed2005

Identification of a novel insulin-like growth factor binding protein gene homologue with tumor suppressor like properties.

Here we report the identification of a new insulin-like growth factor binding protein homologue, provisionally designated insulin-like growth factor binding related protein-4 (IGFBP-rP4). IGFBP-rP4 was found to be most closely related to IGFBP-7 with 52% amino acid homology and 43% amino acid identity, and shares a similar domain structure. Semi-quantitative RT-PCR expression analysis demonstrated a pattern of downregulation of this gene in multiple tumor samples including lung and colon cancer, compared to matched adjacent normal tissue. Western blotting revealed a protein of approximately 38kDa expressed in both the cell pellet and secreted into the supernatant of transiently transfected Cos-7 cells. Cos-7 supernatants containing IGFBP-RP4 protein were observed to suppress the growth of HeLa cells in culture compared to vector controls. IGFBP-RP4 directly transiently transfected into HeLa cells also further confirmed the growth suppressive properties of this protein. Together these data suggest that IGFBP-RP4 may be a novel putative tumor suppressor protein.

Amino Acid Sequence↗
PubMed2001

The role of recombination activating gene (RAG) reinduction in thymocyte development in vivo.

Assembly of T cell receptor (TCR)alpha/beta genes by variable/diversity/joining (V[D]J) rearrangement is an ordered process beginning with recombination activating gene (RAG) expression and TCRbeta recombination in CD4(-)CD8(-)CD25(+) thymocytes. In these cells, TCRbeta expression leads to clonal expansion, RAG downregulation, and TCRbeta allelic exclusion. At the subsequent CD4(+)CD8(+) stage, RAG expression is reinduced and V(D)J recombination is initiated at the TCRalpha locus. This second wave of RAG expression is terminated upon expression of a positively selected alpha/beta TCR. To examine the physiologic role of the second wave of RAG expression, we analyzed mice that cannot reinduce RAG expression in CD4(+)CD8(+) T cells because the transgenic locus that directs RAG1 and RAG2 expression in these mice is missing a distal regulatory element essential for reinduction. In the absence of RAG reinduction we find normal numbers of CD4(+)CD8(+) cells but a 50-70% reduction in the number of mature CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. TCRalpha rearrangement is restricted to the 5' end of the Jalpha cluster and there is little apparent secondary TCRalpha recombination. Comparison of the TCRalpha genes expressed in wild-type or mutant mice shows that 65% of all alpha/beta T cells carry receptors that are normally assembled by secondary TCRalpha rearrangement. We conclude that RAG reinduction in CD4(+)CD8(+) thymocytes is not required for initial TCRalpha recombination but is essential for secondary TCRalpha recombination and that the majority of TCRalpha chains expressed in mature T cells are products of secondary recombination.

Animals↗
PubMed2001

Proton-lithium binding behavior of tris(2-((pyrid-2-ylmethyl)uredio)ethyl)amine.

Tris(2-((pyrid-2-ylmethyl)uredio)ethyl)amine (2) and its perchlorate salt, 2.HClO(4), bind with Li+ in nitromethane in a 1:1 fashion. The stability constants of K(Li+) and K(H)(Li+) were found to be 112 +/- 25 and 130 +/- 30 M(-)(1) in CD(3)NO(2), respectively. Formation of the 1:1 complexes were further evidenced by electrospray ionization mass spectrometry (ESI-MS). The slight increase, or at least the same order of magnitude, of K(H)(Li+) compared to K(Li+) points to a remarkable preorganization of the protonated podand in 2.HClO(4), that essentially overcomes the increased Columbic repulsion occurring on complexation to Li+.

Journal Article↗
PubMed2001

Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development.

DNA ligase IV (Lig4) and the DNA-dependent protein kinase (DNA-PK) function in nonhomologous end joining (NHEJ). However, although Lig4 deficiency causes late embryonic lethality, deficiency in DNA-PK subunits (Ku70, Ku80, and DNA-PKcs) does not. Here we demonstrate that, similar to p53 deficiency, ataxia-telangiectasia-mutated (ATM) gene deficiency rescues the embryonic lethality and neuronal apoptosis, but not impaired lymphocyte development, associated with Lig4 deficiency. However, in contrast to p53 deficiency, ATM deficiency enhances deleterious effects of Lig4 deficiency on growth potential of embryonic fibroblasts (MEFs) and genomic instability in both MEFs and cultured progenitor lymphocytes, demonstrating significant differences in the interplay of p53 vs. ATM with respect to NHEJ. Finally, in dramatic contrast to effects on Lig4 deficiency, ATM deficiency causes early embryonic lethality in Ku- or DNA-PKcs-deficient mice, providing evidence for an NHEJ-independent role for the DNA-PK holoenzyme.

Animals↗
PubMed2001

Clinical analysis and literature review of massive duodenal diverticular bleeding.

A duodenal diverticulum (DD) appears in 2.5% of upper gastrointestinal (UGI) examinations and up to 22% of endoscopic retrograde cholangiopancreaticographies (ERCP) and autopsies. Most of these patients are asymptomatic, but the lesion is occasionally associated with bleeding, inflammation, perforation, obstruction of the duodenum or biliary-pancreatic duct (or both), fistula formation in the bile duct, and bezoar formation inside the diverticulum. A total of 816 patients have undergone ERCP examination at our institution since January 1987, and 100 (12.25%) of them have DD. Seven (7%) patients presented with bloody or tarry stools from massive UGI bleeding followed by shock. Only two could be diagnosed by UGI endoscopy preoperatively. The lesions were demonstrated in angiographic studies in another four cases. However, only one was correctly interpreted and one required reoperation after a correct repeat endoscopic finding. The lesions in the other two patients were identified by thorough exploration during laparotomy. The remaining case was diagnosed by intraoperative endoscopy via pyloroduodenotomy. Six underwent surgical intervention, and one was successfully treated by expectant treatment. Three (50%) had leakage from the duodenotomy but recovered uneventfully with conservative treatment. In conclusion, we believe that DD bleeding is more frequent than usually thought. A high index of suspicion should be raised in cases of UGI bleeding when more obvious and common causes have been excluded by routine endoscopy. Aggressive but careful endoscopic examination combined with accurate angiography can help us diagnose most of the cases preoperatively. Diverticulectomy is an effective surgical procedure, though it is associated with a considerable leakage rate. The morbidity is minimal if we can identify the lesion earlier and evacuate the lesion without delay.

Angiography↗
PubMed2001

Giant ethmoid osteoma with orbital extension, a nasoendoscopic approach using an intranasal drill.

OBJECTIVE: Ethmoid osteoma is a slow-growing, benign, and encapsulated bony tumor. Symptoms occur earlier than with osteomas of the frontal sinus because of the small volume of the ethmoid sinus. Interestingly, orbital extension is uncommon. Treatment remains controversial, with open procedures typically being used. In this article, we present a less invasive yet safe and effective approach to treatment. STUDY DESIGN: A nasoendoscopic approach using a Stammberger-Saches intranasal drill was developed for treatment of patients with ethmoid osteoma, with or without orbital extension. Between 1995 to 1999, seven patients underwent the new surgical procedure. METHODS: All procedures were performed under general anesthesia. Using 0 degrees and 30 degrees endoscopes, surface anesthesia of the nasal mucosa was performed, the anterior ethmoid cell was resected, and the whitish osteoma found. The osteoma was drilled out inferolaterally to superomedially. In the patient with orbital extension, a double-ended blunt elevator was used to separate the remaining osteoma from the lamina papyracea and to push the residual osteoma medially toward the nasal septum. With alternate drilling and elevation, the osteoma was gently removed. The surgical site was then packed. RESULTS: The method successfully treated all patients. There were no major complications. The single patient with orbital extension had mild postoperative periorbital ecchymoses. Nasoendoscopy showed normal epithelialization 4 to 6 weeks after surgery. Computed tomography showed no residual tumors 6 months after surgery. CONCLUSION: The 30 degrees nasoendoscopic approach using an intranasal drill provides a good operative field and is a safe and effective technique, with the potential to become the treatment of choice in selected cases.

Adult↗
PubMed2001

Effect of radiation on cytokine and cytokine receptor messenger-RNA profiles in p53 wild and mutated human glioblastoma cell lines.

OBJECTIVE: Glioblastoma cells produce cytokines with proinflammatory or immunosuppressive properties, or both, which, in addition to altered p53 gene expression, have been shown to be associated with glioblastoma resistance to radiotherapy. The reported data concerning cytokines have been isolated and sometimes discordant, and a comprehensive profile analysis of cytokines and their corresponding receptors in irradiated glioblastomas has received limited attention. The object of this study was to test the hypothesis that radiation alone in clinically relevant doses would not significantly alter expression of endogenous cytokines and their receptors in human glioblastoma celll ines with wild-type and mutant p53. DESIGN AND METHOD: Culture specimens of 4 glioblastoma cell lines of different p53 gene expression (U87, U118, U251, U373) were irradiated with cobalt 60 at a dose of 10 Gy. After 48 hours, radiosensitivity was defined through a colony formation assay, cell cycle distribution was analyzed by flow cytometry, and cytokine and cytokine receptor messenger-RNA (mRNA) profiles were defined with an RNase protection assay. Different single doses of radiation at varying time intervals after culture were applied also to wild-type p53 cell lines. RESULTS: All cell lines were relatively radioresistant at lower doses of 1 and 2 Gy. Immunosuppressive cytokine and cytokine receptor mRNA of the Th2 (IL-13Ralpha, IL-4) and Th3 family (TGF-beta1, 2 and 3, TGF-betaRI and RII) were expressed. In contrast, only 2 proinflammatory Th1 cytokine receptor genes (IFN-gammaRa and IFN-gammaRbeta), but no significant Th1 cytokine gene expression, were detected. Even though the population examined included a large fraction of reproductively dead cells, cytokine and cytokine receptor mRNA profiles were not altered significantly by irradiation in all cell lines, regardless of the p53 status. CONCLUSION: These results suggest that cobalt irradiation alone at clinically relevant doses does not significantly alter the cytokine and cytokine receptor profiles in human glioblastoma cell lines.

Cobalt Radioisotopes↗
PubMed2001

Primary renal sarcoma with inferior vena cava thrombus presenting with tumor rupture.

Primary renal sarcoma represents approximately one per cent of all primary tumors of the kidney in adults. We report an unusual case of primary renal sarcoma with inferior vena cava (IVC) thrombus. This patient presented with hemorrhagic shock due to tumor rupture. Emergent radical nephrectomy and vena caval thrombectomy were performed. Histological examination proved a clear cell sarcoma.

Adult↗
PubMed2000

Response to RAG-mediated VDJ cleavage by NBS1 and gamma-H2AX.

Genetic disorders affecting cellular responses to DNA damage are characterized by high rates of translocations involving antigen receptor loci and increased susceptibility to lymphoid malignancies. We report that the Nijmegen breakage syndrome protein (NBS1) and histone gamma-H2AX, which associate with irradiation-induced DNA double-strand breaks (DSBs), are also found at sites of VDJ (variable, diversity, joining) recombination-induced DSBs. In developing thymocytes, NBS1 and gamma-H2AX form nuclear foci that colocalize with the T cell receptor alpha locus in response to recombination activating gene (RAG) protein-mediated VDJ cleavage. Our results suggest that surveillance of T cell receptor recombination intermediates by NBS1 and gamma-H2AX may be important for preventing oncogenic translocations.

Amino Acid Sequence↗
PubMed2000

DNA repair protein Ku80 suppresses chromosomal aberrations and malignant transformation.

Cancer susceptibility genes have been classified into two groups: gatekeepers and caretakers. Gatekeepers are genes that control cell proliferation and death, whereas caretakers are DNA repair genes whose inactivation leads to genetic instability. Abrogation of both caretaker and gatekeeper function markedly increases cancer susceptibility. Although the importance of Ku80 in DNA double-strand break repair is well established, neither Ku80 nor other components of the non-homologous end-joining pathway are known to have a caretaker role in maintaining genomic stability. Here we show that mouse cells deficient for Ku80 display a marked increase in chromosomal aberrations, including breakage, translocations and aneuploidy. Despite the observed chromosome instabilities, Ku80-/- mice have only a slightly earlier onset of cancer. Loss of p53 synergizes with Ku80 to promote tumorigenesis such that all Ku80-/- p53-/- mice succumb to disseminated pro-B-cell lymphoma before three months of age. Tumours result from a specific set of chromosomal translocations and gene amplifications involving IgH and c-Myc, reminiscent of Burkitt's lymphoma. We conclude that Ku80 is a caretaker gene that maintains the integrity of the genome by a mechanism involving the suppression of chromosomal rearrangements.

Animals↗
PubMed2000

Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-null cells are unrelated to DNA repair defects.

While the Ku complex, comprised of Ku70 and Ku80, is primarily involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type or Ku80-null (Ku80(-/-)) mice with various stress agents revealed that hydrogen peroxide (H(2)O(2)) was markedly more cytotoxic for Ku80(-/-) MEFs and led to their long-term accumulation in the G2 phase. This differential response was not due to differences in DNA repair, since H(2)O(2)-triggered DNA damage was repaired with comparable efficiency in both Wt and Ku80(-/-) MEFs, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and G2-progression are not only dependent on the cell's DNA repair but also may reflect Ku80's influence on additional cellular processes such as gene expression.

Animals↗
PubMed2000

Structure of a (Cys3His) zinc ribbon, a ubiquitous motif in archaeal and eucaryal transcription.

Transcription factor IIB (TFIIB) is an essential component in the formation of the transcription initiation complex in eucaryal and archaeal transcription. TFIIB interacts with a promoter complex containing the TATA-binding protein (TBP) to facilitate interaction with RNA polymerase II (RNA pol II) and the associated transcription factor IIF (TFIIF). TFIIB contains a zinc-binding motif near the N-terminus that is directly involved in the interaction with RNA pol II/TFIIF and plays a crucial role in selecting the transcription initiation site. The solution structure of the N-terminal residues 2-59 of human TFIIB was determined by multidimensional NMR spectroscopy. The structure consists of a nearly tetrahedral Zn(Cys)3(His)1 site confined by type I and "rubredoxin" turns, three antiparallel beta-strands, and disordered loops. The structure is similar to the reported zinc-ribbon motifs in several transcription-related proteins from archaea and eucarya, including Pyrococcus furiosus transcription factor B (PfTFB), human and yeast transcription factor IIS (TFIIS), and Thermococcus celer RNA polymerase II subunit M (TcRPOM). The zinc-ribbon structure of TFIIB, in conjunction with the biochemical analyses, suggests that residues on the beta-sheet are involved in the interaction with RNA pol II/TFIIF, while the zinc-binding site may increase the stability of the beta-sheet.

Amino Acid Motifs↗
PubMed1999

Involvement of farnesyl protein transferase (FPTase) in FcarepsilonRI-induced activation of RBL-2H3 mast cells.

Changes in farnesyl protein transferase (FPTase) activity and FPTase beta-subunit protein levels were determined in IgE-sensitized RBL-2H3 mast cells in response to polyvalent antigen administration. Ten minutes after the addition of DNP modified BSA to mast cells, whose high affinity receptor for IgE (FcvarepsilonRI) contained bound anti-DNP IgE, FPTase specific activity increased by 54 +/- 28%. Time course studies showed FPTase specific activity doubled during a 20- to 30-min period after antigen-induced cell aggregation. Also, an increase in FPTase beta-subunit protein during this time ( approximately 30%) was observed; this protein increase was not accompanied by a similar increase in FPTase beta-subunit m-RNA levels. The FcvarepsilonRI aggregation had no significant effect on the activities of other enzymes involved with farnesyl diphosphate (FPP) metabolism: FPP synthase, isopentenyl diphosphate isomerase, geranylgeranyl protein transferase, and squalene synthase. Specific inhibition of FPTase activity by manumycin was studied to determine what role FPTase plays in mast cell activation. Manumycin profoundly inhibited hexosaminidase release in activated cells, indicating FPTase is required for signal transduction involved with protein exocytosis from RBL-2H3 mast cells.

Alkyl and Aryl Transferases↗
PubMed1999

Correlation of clinical and ultrasonographic features in congenital muscular torticollis.

OBJECTIVE: To find the relationship between the ultrasonographic pictures and the clinical features of patients with congenital muscular torticollis (CMT). DESIGN: Prospective survey of patients with clinically suspected CMT by high-resolution ultrasonography. SETTING: Rehabilitation department of a tertiary care center. PARTICIPANTS: Two hundred fifty-six CMT patients, from the ages of 9 days to 16yrs, with a mean follow-up period of 6.7 months. MAIN OUTCOME MEASURES: Correlation of the ultrasound appearance of the involved sternocleidomastoid (SCM) muscles with clinical features. The pathologic findings in diseased muscles from patients who underwent surgical intervention were also evaluated. RESULTS: Muscle abnormalities were identified ultrasonographically in 218 CMT patients (85%) and were classified into four types: a fibrotic mass in the involved muscle (type I, 15%); diffuse fibrosis mixing with normal muscle (type II, 77%) and without normal muscle in the involved muscle (type III, 5%); and a fibrotic cord in the involved muscle (type IV, 3%). Compared with type I patients, type IV patients were more likely to undergo surgical treatment (odds ratio = 31.54, p = .0196). Type III patients were more likely to undergo surgical treatment, although this tendency was not statistically significant. CONCLUSION: Ultrasonography can precisely identify pathologic changes in the involved SCM muscle of CMT patients. Type III and IV patients are more likely to require surgical intervention.

Adolescent↗
PubMed1999

Differential binding of proteins to peroxisomes in rat hepatoma cells: unique association of enzymes involved in isoprenoid metabolism.

Farnesyl diphosphate synthase (FPPS: EC2.5.1.10), a key enzyme in isoprenoid metabolic pathways, catalyzes the synthesis of farnesyl diphosphate (FPP) an intermediate in the biosynthesis of both sterol and non-sterol isoprenoid end products. The localization of FPPS to peroxisomes has been reported (Krisans, S. K., J. Ericsson, P. A. Edwards, and G. A. Keller. 1994. J. Biol. Chem. 269: 14165;-14169). Using indirect immunofluorescence and immunoelectron microscopic techniques we show here that FPPS is localized predominantly in the peroxisomes of rat hepatoma H35 cells. However, the partial release of 60;-70% of cellular FPPS activity is observed by selective permeabilization of these cells with digitonin. Under these conditions, lactate dehydrogenase, a cytosolic enzyme, is completely released whereas catalase, a known peroxisomal enzyme, is fully retained. Digitonin treatment of H35 cells differentially affects the release of other peroxisomal enzymes involved in isoprenoid metabolism. For instance, mevalonate kinase and phosphomevalonate kinase are almost totally released (95% and 91%, respectively), whereas 3-hydroxy-3-methylglutaryl-CoA reductase is fully retained. Indirect immunoflourescence studies indicate that FPPS is localized in peroxisomes of Chinese hamster ovary (CHO)-K1 cells but is dispersed in the cytosol of ZR-82 cells, a mutant that lacks peroxisomes. Unlike in H35 cells, FPPS is completely released upon digitonin permeabilization of CHO-K1 and ZR-82 cells. In contrast, under the same permeabilization conditions, catalase is fully retained in CHO-K1 cells but completely released from ZR-82 cells. These studies indicate that FPPS and other enzymes in the isoprenoid biosynthetic pathways, involved in the formation of FPP, are differentially associated with peroxisomes and may easily diffuse to the cytosol. Based on these observations, the significance and a possible regulatory model in the formation of isoprenoid end-products are discussed.

Alkyl and Aryl Transferases↗
PubMed1999

Endoscopic carpal tunnel release.

BACKGROUND: Endoscopic carpal tunnel release was developed by Okutsu and Chow in 1989. Many reports have indicated that endoscopic carpal tunnel release diminishes postoperative pain and accelerates the recovery time. METHODS: In a series of 1278 carpal tunnel release procedures (in 948 patients), 1214 were performed with a modified Menon endoscopic method and the remaining 64 with an open procedure. The patients with idiopathic carpal tunnel syndrome were followed for at least 3 months. RESULTS: Of the endoscopic release patients, 80.9% recovered grip strength equal to or greater than preoperative levels within 4 weeks, whereas in the open procedure group, the rate was only 59.3%. The difference was statistically significant (p = 0.00011). An immediate complication was one median motor nerve severance. There were 24 conversions to a conventional open procedure during endoscopic release. In the endoscopic group, 81% developed scar tenderness over the thenar crease, 31% developed new sensory disturbance, and 4% developed pillar pain. CONCLUSION: Endoscopic release facilitated the recovery of grip strength and diminished the frequency of scar tenderness. However, neurovascular injury should be carefully prevented.

Adult↗
PubMed1998

Regulation of bovine interleukin-1 receptors.

Interleukin-1 is a key player in inflammation and the immune response. The interleukin-1 family consists of three ligands (IL-1 alpha, IL-1 beta, and the IL-1 receptor antagonist) and two receptors (IL-1RI and IL-1RII). Previous studies suggest a dynamic relationship among these receptors and ligands that regulates the magnitude and extent of IL-1 mediated activities. Our laboratory has cloned and sequenced the bovine type I and II interleukin-1 receptors, and has begun to investigate their regulation in bovine leukocytes in vitro and in vivo. IL-1RI and IL-1RII mRNA levels were upregulated in vitro by various mediators, including dexamethasone, rBoIL-4, rBoGM-CSF, and rHuTNF alpha. Conversely, IL-1RI mRNA levels were down-regulated by IFN-gamma. An in vivo study indicated that IL-1RII mRNA levels increased earlier than IL-1RI mRNA levels in dexamethasone-treated cattle. These findings suggest that early upregulation of IL-1RII, which is a decoy receptor, may be part of the anti-inflammatory action of glucocorticoids. Our investigations suggest that anti-inflammatory agents increase expression of the biologically inactive IL-1RII, as compared with the biologically active IL-1RI, in bovine leukocytes.

Animals↗