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Biomedical subjects

H C Chen

Publications and source records attributed to H C Chen.

At least 37 records · Page 2Linked to original sources

Predictive factors for skin telangiectasia following post-mastectomy electron beam irradiation.

This study evaluated the predictive factors associated with skin telangiectasia following post-mastectomy electron beam irradiation of the chest wall and regional lymph nodes in patients with breast cancer. From July 1987 to December 1994, 120 women with stages II and III breast cancer received electron beam irradiation following modified radical mastectomy. Doses of 50-50.4 Gy per 25-28 fractions were given to the chest wall (with bolus), the internal mammary nodes, the supraclavicular nodes and the axillary lymph nodes using a 12 MeV or 15 MeV single portal electron beam. 19 patients received an additional 10-16 Gy boost to the surgical scar using a 9 MeV electron beam. Univariate and multivariate analyses for the development of skin telangiectasia showed 5- and 7-year actuarial rates of telangiectasia to be 59% and 72%, respectively. In univariate analysis, an additional surgical scar boost (p=0.023) as well as no treatment interruption (p=0.028) were associated with a significantly increased risk of skin telangiectasia. In multivariate analysis, the only significant independent factor for the development of skin telangiectasia was surgical scar boost (p=0.026); no treatment interruption showed a trend but did not achieve significance (p=0.051). Thus, patients given an additional boost to the surgical scar are more likely to develop skin telangiectasia. Shorter treatment courses may result in a higher probability of skin telangiectasia following electron beam irradiation.

Adult↗

A new incision for surgery on tendo Achillis using a distally-based fasciocutaneous flap.

The consequences of breakdown of the wound after surgery to tendo Achillis are considerable. Complex surgery is often required to reconstruct the tendon and to provide soft-tissue cover. We describe a new incision which approaches the tendon by using a distally-based fasciocutaneous flap. This reduces the risk of breakdown of the wound since it avoids making an incision directly over the tendon, provides good exposure, and maintains the vascularity of the skin overlying the tendon.

Achilles Tendon↗

Unilateral renal cystic disease--report of one case and review of literature.

Clinical presentation of unilateral renal cystic disease (URCD) is characterized by multiple simple cysts in only 1 kidney. Involvement of other intra-abdominal organs is not found. Renal function is usually preserved despite the existence of multiple cysts. No genetic background can be delineated up to the present. We present 1 patient with URCD, who was evaluated for his right flank pain. Urinalysis and biochemical tests showed normal renal function (BUN 5.03 mmol/l, creatinine 110.5 micromol/l). Ultrasonographic examination was done and it revealed 2 right renal stones. Furthermore, multiple renal cysts over the juxta-medullary area were noted. His left kidney was intact. Computed tomography (CT) of both kidneys confirmed this finding. 99mTc-DTPA renal scan showed that the glomerular filtration rate of both kidneys was not significantly different. There was no family history of renal diseases. His parents, grandparents and siblings were examined for possible kidney lesions, but none of them had any renal cystic lesion. This patient was followed for only a relatively short period of time (3 years) and his renal function did not deteriorate. Follow-up image studies with sonography and CT were not different from the previous ones.

Adult↗

Edema due to protein-losing enteropathy--a disorder rarely considered by nephrologists.

In the differential diagnosis, protein-losing enteropathy (PLE) is a rarely considered explanation of edema. Three such cases are reported in this article. Clinical presentations varied from severe generalized anasarca and respiratory distress to mild pitting edema on the pretibial surface. Hypoalbuminemia (< 35 g/l) was another common finding in addition to edema. The patients were carefully examined to exclude other causes of hypoalbuminemia. Two patients experienced diarrhea. Endoscopic studies (plus biopsies) for any mucosal lesion in the stomach and colon were also performed. PLE was confirmed by the positive radionuclide scanning results after infusing intravenous 99mTc human serum albumin (USA). Investigation for the etiologies showed intestinal lymphangiectasia in 1 patient, Menetrier's disease in another, and no recognizable cause in the third. The severe anasarca of the patient with intestinal lymphangiectasia didn't respond to corticosteroids and albumin supplement plus large doses of furosemide. She died of overwhelming pulmonary infection despite the use of powerful antibiotics (ceftriaxone and amikacin). We planned to treat the Menetrier's disease patient with somatostatin to decrease the exocrine activities of the intestinal tract. The patient with presumable idiopathic PLE had the least severe edema and was not treated with any medication. In addition to the above patients, another 3 patients with hypoalbuminemia and edema were also noted to have positive HSA scan results. However, 2 of these patients had systemic lupus erythromatosus and the third pulmonary tuberculosis and biopsy-proven membranous nephropathy. Treatment of their underlying diseases showed satisfactory remission of edema.

Adult↗

Anti-HIV effects of chloroquine: mechanisms of inhibition and spectrum of activity.

OBJECTIVE: To investigate the mechanisms and spectrum of the anti-HIV activity of chloroquine. DESIGN AND METHODS: MT-4 cells or peripheral blood mononuclear cells were infected with X4, R5 or R5/X4 HIV-1 strains from clades A-E and HIV-2. The cells were then treated with clinically relevant and achievable chloroquine concentrations (i.e. 0-12.5 microM), so as to determine the EC50. The effects of chloroquine on reverse transcription and integration were tested using a replication-defective reporter HIV-1 construct (pRRL.sin.hPGK.GFP). The effects of the drug on the viral envelope were assessed by syncytium assays and immunoprecipitation, using antibodies to different epitopes of gp120. RESULTS: In de-novo infected MT-4 cells, chloroquine selectively inhibited HIV-1 IIIB replication but not pRRL.sin.hPGK.GFP. In chronically HIV-1-infected H9 IIIB cells, chloroquine decreased the infectivity of the newly produced virus and the ability of these cells to form syncytia in co-culture with MT-2 cells. These effects were associated with structural changes in the gp120 glycoprotein, such as a reduction of reactivity with antibodies directed against the glycosylated 2G12 epitope. Although affecting a variable target such as gp120, chloroquine was capable of inhibiting X4, R5 and R5/X4 primary HIV-1 isolates from subtypes A, B, C, D, E and HIV-2. CONCLUSION: At clinically achievable concentrations chloroquine inhibits HIV-1 post-integrationally by affecting newly produced viral envelope glycoproteins, and the drug has broad-spectrum anti-HIV-1 and HIV-2 activity.

Anti-HIV Agents↗

MST4, a new Ste20-related kinase that mediates cell growth and transformation via modulating ERK pathway.

In this study, we report the cloning and characterization of a novel human Ste20-related kinase that we designated MST4. The 416 amino acid full-length MST4 contains an amino-terminal kinase domain, which is highly homologous to MST3 and SOK, and a unique carboxy-terminal domain. Northern blot analysis indicated that MST4 is highly expressed in placenta, thymus, and peripheral blood leukocytes. Wild-type but not kinase-dead MST4 can phosphorylate myelin basic protein in an in vitro kinase assay. MST4 specifically activates ERK but not JNK or p38 MAPK in transient transfected cells or in stable cell lines. Overexpression of dominant negative MEK1 or treatment with PD98059 abolishes MST4-induced ERK activity, whereas dominant-negative Ras or c-Raf-1 mutants failed to do so, indicating MST4 activates MEK1/ERK via a Ras/Raf-1 independent pathway. HeLa and Phoenix cell lines overexpressing wild-type, but not kinase-dead, MST4 exhibit increased growth rate and form aggressive soft-agar colonies. These phenotypes can be inhibited by PD98059. These results provide the first evidence that MST4 is biologically active in the activation of MEK/ERK pathway and in mediating cell growth and transformation.

Amino Acid Sequence↗

Sustained activation of extracellular signal-regulated kinase stimulated by hepatocyte growth factor leads to integrin alpha 2 expression that is involved in cell scattering.

We have previously shown that hepatocyte growth factor (HGF) selectively increases the expression of integrin alpha(2) in Madin-Darby canine kidney (MDCK) cells. In this study, we have further investigated the signal transduction pathways responsible for the event and its role in HGF-induced cell scattering. We found that the level of integrin alpha(2)beta(1) expression induced by HGF correlated with the extent of cell scattering and that a functional blocking antibody against integrin alpha(2) at the concentration of 25 microg/ml partially (40%) inhibited the HGF-induced cell scattering. However, in the presence of the specific phosphatidylinositol 3-kinase inhibitor LY294002 or the selective Src family kinase inhibitor PP1, although cells retained their response to HGF for increasing integrin alpha(2) expression, they failed to scatter, indicating that increased expression of integrin alpha(2) alone is not sufficient for cell scattering. Moreover, epidermal growth factor, which induced a transient (1 h) activation of extracellular signal-regulated kinase (ERK) in MDCK cells, only slightly increased integrin alpha(2) expression and failed to trigger cell scattering. Conversely, HGF induced a sustained (at least 12 h) activation of ERK in the cells. Expression of constitutively active ERK kinase (MEK) in MDCK cells led to increased expression of integrin alpha(2) even in the absence of HGF stimulation. In contrast, expression of ERK phosphatase or dominant negative MEK inhibited HGF-induced integrin alpha(2) expression. Taken together, our results suggest that the increased expression of integrin alpha(2)beta(1) by HGF is at least partially required for cell scattering and that the duration of MEK/ERK activation is likely to be a crucial determinant for cells to activate integrin alpha(2) expression and cell scattering.

Animals↗

Isolation and characterization of major glycoproteins of pigeon egg white: ubiquitous presence of unique N-glycans containing Galalpha1-4Gal.

Ovotransferrin (POT), two ovalbumins (POA(hi) and POA(lo)), and ovomucoid (POM) were isolated from pigeon egg white (PEW). Unlike their chicken egg white counterparts, PEW glycoproteins contain terminal Galalpha1-4Gal, as evidenced by GS-I lectin (specific for terminal alpha-Gal), anti-P(1) (Galalpha1-4Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glcbeta1-1Cer) monoclonal antibody, and P fimbriae on uropathogenic Escherichia coli (specific for Galalpha1-4Gal). Galalpha1-4Gal on PEW glycoproteins were found in N-glycans releasable by treatment with glycoamidase F. The respective contents of N-glycans in each glycoprotein were 3.5%, POT; 17%, POA(hi); and 31-37%, POM. POA(hi) has four N-glycosylation sites, in contrast to chicken ovalbumin, which has only one. High performance liquid chromatography analysis showed that N-glycans on POA(hi) were highly heterogeneous. Mass spectrometric analysis revealed that the major N-glycans were monosialylated tri-, tetra-, and penta-antennary oligosaccharides containing terminal Galalpha1-4Gal with or without bisecting N-acetylglucosamine. Oligosaccharide chains terminating in Galalpha1-4Gal are rare among N-glycans from the mammals and avians that have been studied, and our finding is the first predominant presence of (Galalpha1-4Gal)-terminated N-glycans.

Animals↗

Posttraining infusion of norepinephrine and corticotropin releasing factor into the bed nucleus of the stria terminalis enhanced retention in an inhibitory avoidance task.

The present study investigated whether the bed nucleus of the stria terminalis (BNST) is involved in formation and retrieval of affective memory. Male Wistar rats with cannulae bilaterally implanted into the BNST were trained on a one-trial step-through inhibitory avoidance task. Shortly after training they received bilateral intra-BNST infusion of lidocaine, various noradrenergic drugs, or corticotropin releasing factor (CRF). Results showed that posttraining intra-BNST infusion of lidocaine impaired retention. Posttraining intra-BNST infusion of norepinephrine or the alpha1 antagonist prazosin induced a dose- and time-dependent retention enhancement or deficit, respectively. The enhancing effect of norepinephrine was mimicked by the alpha1 agonist phenylephrine, and antagonized by prazosin at a non-impairing dose. Posttraining intra-BNST infusion of the alpha2 antagonist idazoxan or the beta antagonist propranolol failed to affect retention. Posttraining intra-BNST infusion of CRF also enhanced retention in a dose-dependent manner. Various drugs infused shortly before testing did not significantly influence locomotor activity and retention. These findings, taken together, suggest that the BNST is involved in memory formation processes for affective experience and norepinephrine released in the BNST acting via alpha1 receptors plays a critical role in this function.

Adrenergic alpha-Agonists↗

A physical map of the human genome.

The human genome is by far the largest genome to be sequenced, and its size and complexity present many challenges for sequence assembly. The International Human Genome Sequencing Consortium constructed a map of the whole genome to enable the selection of clones for sequencing and for the accurate assembly of the genome sequence. Here we report the construction of the whole-genome bacterial artificial chromosome (BAC) map and its integration with previous landmark maps and information from mapping efforts focused on specific chromosomal regions. We also describe the integration of sequence data with the map.

Chromosomes, Artificial, Bacterial↗

Role of receptor for advanced glycation end-product (RAGE) and the JAK/STAT-signaling pathway in AGE-induced collagen production in NRK-49F cells.

Advanced glycation end-product (AGE) is important in the pathogenesis of diabetic nephropathy (DN), and captopril (an angiotensin converting enzyme inhibitor) is effective in treating this disorder. We have shown that the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) cascade is responsible for AGE-induced mitogenesis in NRK-49F (normal rat kidney fibroblast) cells, but its role in renal fibrosis in DN remains unknown. Therefore, we have sought to determine whether JAK/STAT is involved in AGE-regulated collagen production in NRK-49F cells. We found that AGE time (1-7 days) and dose (10-200 microg/ml)-dependently increased collagen production in these cells. Additionally, AGE increased RAGE (receptor for AGE) protein expression. AGE-induced RAGE expression was dose-dependently inhibited by antisense RAGE oligodeoxynucleotide (ODN) and captopril. AGE-induced type I collagen production and JAK2-STAT1/STAT3 activation were decreased by AG-490 (a specific JAK2 inhibitor), antisense RAGE ODN and captopril. Meanwhile, STAT1 and STAT3 decoy ODNs also suppressed the induction of collagen by AGE. We concluded that RAGE and the JAK2-STAT1/STAT3 pathway were involved in AGE-induced collagen production in NRK-49F cells. Furthermore, captopril was found to reverse AGE-induced collagen production, probably by attenuating RAGE expression and JAK2-STAT1/STAT3 activities.

Base Sequence↗

Asian multicenter trials on urinary type IV collagen in patients with diabetic nephropathy.

To investigate the changes of renal type IV collagen turnover in diabetic nephropathy, urinary type IV collagen was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA). Urinary samples were obtained from 698 diabetic patients and 191 healthy adults. Among the patients, 264 had urinary albumin levels of less than 29 mg/g.creatine (Cr) (Stage I: normoalbuminuric stage), 169 had microalbuminuria from 30 to 299 mg/g.Cr (Stage II: microalbuminuric stage), 84 patients had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of less than 1.1 mg/dl (Stage IIIA: macroalbuminuric stage without renal dysfunction), 97 had macroalbuminuria of more than 300 mg/g.Cr and serum Cr of more than 1.2 mg/dl (Stage IIIB: macroalbuminuric stage with renal dysfunction), and 84 had renal failure (Stage IV). The levels of urinary type IV collagen in Stages II, IIIA, IIIB, and IV were significantly higher than those in Stage I (P < 0.0001). The level of urinary type IV collagen in Stage I (5.00 +/- 0.23 microg/g.Cr; mean +/- SE) was also higher than that in normal adults (3.44 +/- 0.11 microg/g.Cr; mean +/- SE). These levels increased gradually due to progression of the clinical stage of diabetic nephropathy. It appears that the levels of urinary type IV collagen can be a useful marker for detecting renal injuries in diabetes according to our Asian multicenter trials.

Aged↗

Plasma and urinary endothelin-1 in focal segmental glomerulosclerosis.

The kidney is an important site of endothelin-1 (ET-1) production and is particularly susceptible to ET-1 action. Infusion of ET-1 in rats induces both functional and morphological alterations in the kidneys. Increased plasma level of ET-1 has been reported in patients with chronic renal failure. However, there are still no reports on the plasma and urinary ET-1 levels in patients with focal segmental glomerulosclerosis (FSGS). In the present study, we have measured the plasma concentration and urinary excretion rate of ET-1 in 15 patients with nephrotic syndrome due to FSGS, and observed the serial changes of plasma and urinary ET-1 in nephrotic rats with FSGS, induced by repeated injection with puromycin aminonucleoside (PAN). ET-1 was measured with radioimmunoassay. The results showed that plasma ET-1 concentration in FSGS patients was significantly higher than in normal controls (P < 0.05), and that urinary ET-1 excretion rate was also significantly higher in FSGS patients than in normal controls (P < 0.01). In FSGS patients, the plasma and urinary ET-1 was significantly correlated (P < 0.05), and the urinary ET-1 excretion rate was significantly correlated with the amount of proteinuria (P < 0.05) and the glomerular sclerosing score (P < 0.01). In the ten rats with PAN-induced FSGS, serial examination showed a significant increase in plasma ET-1 after 8 weeks of injections, while the urinary ET-1 excretion rate showed a biphasic increase that showed a peak after 4 to 6 weeks. The same changes in plasma and urinary ET-1 levels were not observed in control rats injected with normal saline at the same frequency. Our results suggest that ET-1 may be involved in the pathogenesis of FSGS in both humans and rats.

Adult↗

Limb preservation by Gore-Tex vascular graft for groin recurrence after postoperative adjuvant radiation in vulvar cancer.

BACKGROUND: Recurrent vulvar cancer involving the femoral artery after groin radiation is usually considered inoperable. A patient with such recurrent vulvar cancer successfully treated by femoral vascular graft and rectus abdominis myocutaneous flap reconstruction with limb salvage is described. CASE: A 51-year-old woman had recurrent vulvar cancer involving the right femoral vessels 6 months after a radical vulvectomy plus inguinal lymphadenectomy and postoperative pelvic and groin radiation. Radical en bloc excision of tumor along with the involved femoral artery and vein followed by Gore-Tex vascular graft and rectus abdominis myocutaneous flap reconstruction led to a complete remission. However, occlusion of the grafted vessels occurred 21 months following bypass surgery. Since the compensatory collaterals were established, debridement and removal of the occluded graft were carried out. The patient has been clinically free of disease for more than 48 months since graft reconstruction surgery. CONCLUSION: It is highlighted that aggressive tumor resection with limb salvage is feasible even for patients with vulvar cancer of the groin recurrence involving the femoral artery after primary surgery and groin radiation.

Blood Vessel Prosthesis↗

G561 site-directed deletion mutant chitinase from Aeromonas caviae is active without its 304 C-terminal amino acid residues.

A G561 mutant of the Aeromonas caviae chitinase ChiA was made by PCR site-directed deletion mutagenesis in order to study the role of the 304 C-terminal amino acid residues of ChiA in the enzymatic hydrolysis of chitin. The recombinant ChiAG561 encoded on a 1.6-kb DNA fragment of A. caviae chiA was expressed in a heterologous Escherichia coli host using the pET20b(+) expression system. The His-Tag-affinity-purified recombinant ChiAG561 had a calculated molecular mass of 63,595 Da, which was consistent with the 67,000 Da estimated by SDS-PAGE. The G561 deletion mutant enzyme had the same optimum pH (6.5) as the full-length ChiA and a lower optimum temperature (37 degrees C instead of 42.5 degrees C). Biochemical properties of the recombinant ChiAG561 suggested that deletion of the 304 C-terminal amino acid residues of ChiA did not significantly affect ChiA enzyme activity. However, compared to the full-length ChiA, the mutant chitinase had a ten-fold higher relative activity with 4-methylumbelliferyl-N-N'-N"-triacetylchitotriose [4-MU-(GlcNAc)3] as a substrate, and higher rates of hydrolysis with both chitin and colloidal chitin substrates. Results obtained from this study suggest that the active region of A. caviae ChiA is located in the region before G561 of the protein molecule.

Aeromonas↗

The development of phonological awareness: effects of spoken language experience and orthography.

Phonological awareness, the ability to analyze spoken language into small sound units, has been shown to be affected by the individual's early orthographic experience (alphabetic vs. non-alphabetic). Past studies, however, have not differentiated the effect of script alphabeticity from that of spoken language experience, which covaries strongly with the phonological properties of the language. The present study compares younger, pre-reading to older, literate children from different linguistic backgrounds on their phonological awareness. Hong Kong and Guangzhou subjects both spoke Cantonese. The latter subjects had early experience with Pinyin (alphabetic) in addition to their logographic Chinese reading; the former read only logographic Chinese. New Zealand subjects spoke English and read the Roman alphabet. Results showed that: (1) the Hong Kong and Guangzhou pre-readers performed very similarly at all levels of phonological awareness; (2) the New Zealand pre-readers outperformed their Hong Kong and Guangzhou counterparts on onset, rime, and coda analyses; (3) the Guangzhou reading children outperformed their Hong Kong counterparts on onset and coda analyses. Whereas finding (3) reflects an effect of alphabeticity in the first learned script, finding (2) in combination with finding (1) indicates an effect of early spoken language experience independent of orthography. The fact that orthographic and spoken language experience both impact on the development of phonological skills implies a mediating function of phonological awareness in integrating sound information derived from reading and perceiving speech.

Age Factors↗

Thermo-debonding mechanisms in dentin bonding systems using finite element analysis.

The finite element method (FEM) has been extensively used in evaluating the interfacial status of biomaterials. We used FEM to explore the microscopic debonding mechanism of the dentin/hybrid layer/resin adhesive interface. The stress status of the local material was used as an index to judge whether the adhesive interface would develop a debonding mechanism. To generate the local stress concentration, the thermal boundary condition was applied to the model which has the phenomenon of the coefficient of thermal expansion (CTE) mismatch. The thermal boundary condition was used to emulute a previous study conducted with a laser thermoacoustic technique (LTAT). The materials, Scotchbond MP, Optibond, and Tenure bonding systems, used in the previous experiment were also tested in this study. The results show that interfacial debonding in the finite element model occurred through the hybrid layer for both the Scotchbond MP and Tenure systems, as well as within the adhesive layer itself for the Optibond system. These findings are compatible with observations by SEM obtained by LTAT. Another transformed model was created to test the "elastic cavity wall" concept. The result also confirms the importance of the elastic cavity wall concept. These compatible results between FEM and LTAT indicate that FEM can be a very useful supplement to thermoacoustic testing.

Biocompatible Materials↗