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Biomedical subjects

H C Chen

Publications and source records attributed to H C Chen.

At least 127 records · Page 7Linked to original sources

Surgical management of complete ureteric duplication abnormalities in children.

BACKGROUND: A variety of clinical problems due to complete ureteric duplication (CUD) in children may be encountered. Surgical management of CUD varies and is controversial. Therefore, we reviewed the cases of 15 children with CUD operated on at our hospital in an effort to evaluate the various facets of this disorder that influenced our surgical management. METHODS: Fifteen children with abnormalities associated with CUD underwent surgery from 1987 to 1998. There were 14 girls and one boy. Their age at surgery ranged from 15 days to 3.5 years (average, 9.5 months). All children underwent ultrasonography, including 10 intravenous urograms and five prenatal examinations. The anatomic abnormalities of all children were noted according to the Weigert-Meyer rule. RESULTS: Six of 15 ultrasonograms were misinterpreted as hydronephrosis only, while the 10 intravenous urograms were interpreted correctly as CUD. Four patients had recurrent urinary tract infections after surgery. Two of them underwent further surgery, one for stone formation in the residual ureter stump and the other for persistent ureterocele. There was one surgical complication after an upper pole nephroureterectomy. It involved ureteric necrosis with urine leakage. This patient underwent ipsilateral lower pole nephrectomy 28 days after the first operation. All children remained symptom-free during follow-up. CONCLUSIONS: Accurate diagnosis of duplex kidney requires careful imaging studies, especially for fetal renal abnormalities. Management of CUD should be individualized. Usually, upper pole nephroureterectomy is performed for a nonfunctioning moiety. For functioning segments, ureteropyelostomy or ureteric reimplantation can be considered. The results are satisfactory, but long-term follow-up is necessary.

Child, Preschool↗

Hashimoto's encephalopathy.

Hashimoto's encephalopathy is a subacute condition associated with autoimmune thyroiditis. Its presentation varies from focal neurologic deficits to global confusion. Unlike encephalopathy associated with hypothyroidism, Hashimoto's encephalopathy responds to steroid therapy and not thyroxine replacement.

Brain Diseases↗

Reconstruction of upper chest wall defects with a function-preserving pectoralis major muscle flap: case report.

The pectoralis major muscle or myocutaneous flap has a nearly 100% success rate in reconstructing chest wall defects. Major adverse sequelae resulting from the use of the pectoralis major muscle or myocutaneous flap are rarely reported in the literature. However, the loss of pectoralis major muscle function caused by the detachment of the muscle from its insertion on the humeral bone is of more and more concern. This is a significant loss for manual laborers when the patient tries to handle tools or control heavy machinery. A case of upper sternal osteomyelitis is reported. After wide debridement with partial excision of the sternum, the second and third ribs, the right pleura, and the lung were exposed. A right unilateral pectoralis major muscle flap was transposed to restore the defect. In addition, to preserve the lateral portion of the muscle and its insertion on the humerus, the origin of the lower sternocostal part of the pectoralis major muscle was transposed to the medial clavicle and residual upper sternum. In this way, not only was the chest wall defect reconstructed but the function of the residual pectoralis major muscle was also preserved. Postoperative follow-up at one year demonstrated no arm weakness, no limitation in shoulder range of motion, and no evidence of atrophy of the transposed pectoralis major muscle. Our experience with this function-preserving pectoralis major muscle flap was encouraging and we suggest it be employed in the reconstruction of the upper anterior chest wall.

Abscess↗

Elective neck irradiation for nasopharyngeal carcinoma.

BACKGROUND: This study was conducted to evaluate the effectiveness of elective neck irradiation (ENI) for nasopharyngeal carcinoma (NPC), and to analyze factors associated with ENI failure. METHODS: A radiation port covering the side of a neck without gross nodal metastasis was qualified for evaluation of the effectiveness of ENI. From 1988 through 1992, a total of 261 patients with N0 (130 cases), N1 (91 cases), and N3 (40 cases) NPCs were studied. All patients were irradiated with 60Co teletherapy or 10 MV x-ray to a total dose of 46.8 Gy/26 fractions, followed by a boost treatment to the primary site to a total dose of 64.8 to 75.6 Gy/36-42 fractions. All ENI ports received irradiation to a dose of 46.8 to 60.8 Gy. The duration of follow-up was 6 to 10 years, with a median of 8.1 years. Factors associated with to the risk of ENI failure were analyzed. RESULTS: (1) The overall 5-year actuarial local control rate and actuarial survival rate were 74% and 63%, respectively. (2) Among the 261 cases in which ENI treatment was used, the treatment failed in 12 cases, accounting for a crude ENI failure rate of 5%. The overall 5- and 10-year cumulative risk of ENI failure was 5% and 7%, respectively. (3) Time from the start of treatment to ENI failure ranged from 9 to 66 months, with a median of 17 months. (4) Of the 12 patients for whom EMI failed, 11 (92%) had recurrence in the upper neck, and one in the lower neck. (5) Existence of prior failure at the primary site was the only factor significantly correlated with the risk of ENI failure (p < 0.001). The 5-year cumulative risk of ENI failure for patients with local failure vs. those without was 16% vs. 1% (p < 0.0001). CONCLUSION: Moderate-dose ENI was highly effective in the control of subclinical disease in the neck for NPC. ENI failure was closely associated with prior failure at the primary site, implying that local primary tumor failure may lead to an increased potential for metastasis to the neck.

Adult↗

Suppression of ultraviolet irradiation-induced apoptosis by overexpression of focal adhesion kinase in Madin-Darby canine kidney cells.

Focal adhesion kinase (FAK) has been implicated to play a role in suppression of apoptosis. In this study, we have demonstrated that UV irradiation induced cleavage of FAK and two of its interacting proteins Src and p130(Cas) in Madin-Darby canine kidney cells, concomitant with an increase in cell death. The cleavage of these proteins upon UV irradiation was completely inhibited by ZVAD-FMK, a broad range inhibitor of caspases, and apparently delayed by Bcl2 overexpression. To examine if FAK plays a role in suppressing UV-induced apoptosis, stable Madin-Darby canine kidney cell lines overexpressing FAK were established. Our results showed that a marked (30-40%) increase in cell survival upon UV irradiation was achieved by this strategy. In our efforts to determine the mechanism by which FAK transduces survival signals to the downstream, we found that a FAK mutant deficient in binding to phosphatidylinositol 3-kinase failed to promote cell survival. Moreover, the expression of the Src homology 3 domain of p130(Cas), which competed with endogenous p130(Cas) for FAK binding, abrogated the FAK-promoted cell survival. Together, these results suggest that the integrity of FAK and its binding to phosphatidylinositol 3-kinase and p130(Cas) are required for FAK to exert its antiapoptotic function.

Animals↗

Proteolytic fragments of anti-HIV and anti-tumor proteins MAP30 and GAP31 are biologically active.

We analyzed the structural and functional organization of anti-HIV and anti-tumor proteins MAP30 and GAP31 by limited proteolysis with endopeptidases Lys-C and Glu-C (V8). MAP30 and GAP31 are resistant to proteolytic digestion under conditions of as much as 5% (w/w) proteases. In the presence of 10% (w/w) protease, the central regions of the proteins are still resistant to proteolysis, whereas the N- and C-termini are accessible. Peptide fragments were purified by FPLC on Superdex 75 columns, characterized by gel electrophoresis, identified by amino acid sequencing, and analyzed for anti-HIV, anti-tumor, and other biochemical activities. We report here that limited proteolysis yields biologically active fragments of both MAP30 and GAP31. These fragments are active against HIV-1 and tumor cells with EC(50)s in the sub-nanomolar ranges, 0.2-0.4 nM. At the dose levels used in the assays, little cytotoxicity to normal cells was observed. In addition, these fragments remain fully active in HIV-integrase inhibition and HIV-LTR topological inactivation, but not ribosome inactivation. These results demonstrate that the antiviral and anti-tumor activities of MAP30 and GAP31 are independent of ribosome inactivation activity. In addition, we demonstrate that portions of the N- and C-termini are not essential for antiviral and anti-tumor activities, but do appear to be required for ribosome inactivation. These results may provide novel strategies for rational design and targeted development of mimetic antiviral and anti-tumor therapeutics.

Amino Acid Sequence↗

Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells.

Advanced glycation end product (AGE) is important in the pathogenesis of diabetic nephropathy, which is characterized by cellular hypertrophy/hyperplasia leading to renal fibrosis. However, the signal transduction pathways of AGE remain poorly understood. The Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway has been associated with cellular proliferation in some extra-renal cells. Because interstitial fibroblast proliferation might be important in renal fibrosis, we studied the role of the JAK/STAT pathway in NRK-49F (normal rat kidney fibroblast) cells cultured in AGE/BSA and non-glycated BSA. We showed that AGE dose-dependently (10-200 microgram/ml) increased cellular mitogenesis in NRK-49F cells at 5 and 7 days. However, cellular mitogenesis was unaffected by the simultaneous presence of BSA. Regarding the JAK/STAT pathway, AGE (100 microgram/ml) induced tyrosine phosphorylation of JAK2 (but not JAK1, JAK3 or TYK2) at 15-60 min; it also induced the tyrosine phosphorylation of STAT1 and STAT3 at 1-2 h and 0.5-4 h respectively. Being a transcription factor, AGE also increased the DNA-binding activities of STAT1 and STAT3 AG-490 (a specific JAK2 inhibitor) (5 microM) inhibited tyrosine phosphorylation of JAK2 and the DNA-binding activities of STAT1 and STAT3. The same results were obtained by using specific 'decoy' oligodeoxynucleotides (ODNs) that prevented STAT1 and STAT3 from binding to DNA. Meanwhile, the STAT1 or STAT3 decoy ODN and AG-490 were effective in reversing AGE-induced cellular mitogenesis. We concluded that the JAK2-STAT1/STAT3 signal transduction pathway is necessary for AGE-induced cellular mitogenesis in NRK-49F cells.

Animals↗

Steroid hormones: Interactions with membrane-bound receptors.

Steroid hormones are generally thought to pass easily across a plasma membrane into a cell, interacting once inside with soluble nuclear receptors, but recent experiments have demonstrated the importance of membrane-bound receptors in mediating the activity and the metabolism of steroid hormones.

Animals↗

Alteration of hMSH2 and DNA polymerase beta genes in breast carcinomas and fibroadenomas.

Genomic stability is preserved by error-free DNA replication, post-replicative proofreading, DNA repair, and recombinational events. In essence, DNA repair genes are recognized to play key roles in such stability. We report evidence for expression of the wild-type and a truncated form of DNA polymerase beta (polbeta) proteins, a base-excision repair gene, in breast carcinomas and fibroadenomas, a benign breast disease. An 87-bp deleted variant of polbeta was identified to be prevalent in microsatellite unstable breast tumors and fibroadenomas. A large deletion of 1476 bp, as well as point mutations in human MutS homolog 2 (hMSH2) cDNA, was revealed in breast carcinomas. The protein truncation assay confirmed the 1476-bp deletion as a premature protein. This is the first evidence for variant forms of hMSH2 that are associated with breast cancer. Genomic instability in the hMSH2 and polbeta genes may facilitate the occurrence of mutator phenotype in breast cancer.

Breast Neoplasms↗

Computed tomography findings of bony regeneration after radiotherapy for nasopharyngeal carcinoma with skull base destruction: implications for local control.

PURPOSE: To evaluate the response of bony destruction (BD) of the skull base following radiotherapy in nasopharyngeal carcinoma (NPC) and investigate the implications of bony regeneration (BR) on local control and its related factors. METHODS AND MATERIALS: Ninety patients with NPC with skull base destruction clearly demonstrated on computed tomography (CT) were reviewed. These patients have completed the prescribed treatment and received regular CT follow-up. A total of 338 sets of CT images of the head and neck were reviewed. The tumor response and the appearance of BR in the previous destructive part of the skull base were recorded and analyzed. The tumor response was divided into complete, partial, or no response. BR was defined as recalcification or sclerotic change with partial or complete healing in the previous osteolytic bony defect. Local failure was confirmed either by pathological or merely by imaging studies showing progression of tumor in consecutive radiological pictures. RESULTS: The distribution of specific sites of bony destruction (BD) in these patients included the sphenoid bone (68%), paracavernous sinus area (48%), petrous apex (47%), clivus (44%), pterygoid plates (20%), and others (7%). The CT showed 57 patients (63%) had BR. All were observed within 1 year after treatment. Sixty-two patients (69%) had complete tumor response after treatment. Analyzed by logistic regression method, tumor response after treatment was found to have a statistically significant correlation with BR (p = 0.0004). Most BR (55/57) was demonstrated in patients with complete tumor response. The 3-year actuarial local control rate was 54 % in these patients. The local control was quite different in the comparison of patients with BR versus those with persistent BD (77% vs. 21%, p < 0.0001). Multivariate analysis showed that patients with complete tumor response or with BR on imaging had statistically better local control than those without either of the two findings (p < 0.05). CONCLUSION: Appearance of BR at previous destructive skull base following radiotherapy for NPC patients could be clearly demonstrated on CT. Bony regeneration significantly correlated with treatment response and local control. Although the underlying significance of BR was unknown, to predict the outcome after treatment, the appearance of BR shown on CT may imply the complete eradication of tumor in this area.

Adolescent↗

Requirement of phosphatidylinositol 3-kinase in focal adhesion kinase-promoted cell migration.

We have previously shown that overexpression of focal adhesion kinase (FAK) in Chinese hamster ovary (CHO) cells promoted their migration on fibronectin. This effect was dependent on the phosphorylation of FAK at Tyr-397. This residue was known to serve as a binding site for both Src and phosphatidylinositol 3-kinase (PI3K), implying that either one or both are required for FAK to promote cell migration. In this study, we have examined the role of PI3K in FAK-promoted cell migration. We have demonstrated that the PI3K inhibitors, wortmannin and LY294002, were able to inhibit FAK-promoted migration in a dose-dependent manner. Furthermore, a FAK mutant capable of binding Src but not PI3K was generated by a substitution of Asp residue 395 with Ala. When overexpressed in CHO cells, this differential binding mutant failed to promote cell migration although its association with Src was retained. Together, these results strongly suggest that PI3K binding is required for FAK to promote cell migration and that the binding of Src and p130(Cas) to FAK may not be sufficient for this event.

Amino Acid Sequence↗

Lysozyme and RNases as anti-HIV components in beta-core preparations of human chorionic gonadotropin.

Human chorionic gonadotropin (hCG) preparations contain activity against HIV type 1 (HIV-1). However, there has been controversy about whether some biological activities of hCG beta-subunit (hCGbeta) preparations are caused by the beta-subunit itself or other proteins present in the preparations. We report here the purification, characterization, and identification of three enzymes with anti-HIV activity present in the beta-core fraction of hCGbeta prepared from the urine of pregnant women. The N-terminal amino acid sequence of one protein is identical to human urinary lysozyme C, and those of the other two are identical to human RNase A and urinary RNase U. We thus refer to these proteins as AVL (antiviral lysozyme) and AVR (antiviral RNases). In addition to HIV-1 inhibition, AVL is capable of lysing Micrococcus lysodeikticus. AVR digests a variety of RNA substrates, including RNA from HIV-1-infected cells. We also find that lysozyme from chicken egg white, human milk, and human neutrophils and RNase A from bovine pancreas possess activity against HIV-1. These findings may offer additional strategies for the treatment of HIV-1 infection.

Amino Acid Sequence↗

Revascularization of turnover sternum: A definitive treatment for intractable funnel chest.

Twelve intractable funnel chests in young adults were treated with revascularization of the turnover sternum. The sternum and costal composite tissue were resected at the outskirt of the depressed area. Special attention was paid to the dissection of the vascular pedicle at both sides of the internal mammary vessels. The recipient vessels at one side were left long, so were the donor vessels at the other side. A segment of the rib at the exit of the recipient internal mammary vessels had to be removed to accommodate the vessels and to facilitate vascular anastomosis. Vascular anastomosis was accomplished with loupes (Keeler, sixfold magnification) in five patients because the direction of the vessels is vertically oriented. In four cases, artery and vein grafts were taken from the other side of the internal mammary vessels not bound for vascular anastomosis for length discrepancy of the vessels, while the remaining cases had direct vascular anastomosis without vascular grafting. Revascularization of the turnover sternum was performed successfully without vascular compromise. The patients all recovered well with much improved physical condition. Only one patient sustained spontaneous pneumothorax 1 month after the operation. Postoperative three-dimensional computed tomographic (CT) scan revealed increment of thoracic cage volume for 9-17%. Follow-up CT scan 2 years later revealed even more improved thoracic cage expansion.

Adolescent↗

Postoperative radiotherapy in early stage carcinoma of the uterine cervix: treatment results and prognostic factors.

PURPOSE: The objective was to investigate the effect of pathologic parameters and other variables on treatment outcome for patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB, IIA cervical carcinoma, as well as to assess the morbidities attributable to radical surgery combined with postoperative radiotherapy. MATERIALS AND METHODS: Between January 1980 and June 1994, 179 women with FIGO stage IB, IIA carcinoma of the uterine cervix were treated with radical hysterectomy and postoperative irradiation. The median follow-up of alive patients was 6.8 years. All patients received 44-60 Gy external irradiation. One hundred fifty-nine patients received 3-10 Gy intracavitary brachytherapy. The data were analyzed for overall survival, disease-free survival, pelvic control, and treatment-related complications. RESULTS: The 5-year overall survival rate, disease-free survival rate, and pelvic control rate for the 179 patients were 72, 74, and 90%, respectively. The 5-year overall survival rate was 81% for patients without pelvic lymphadenopathy and 53% for those with pelvic lymphadenopathy (P = 0.0000). Other independent prognostic factors for overall survival included tumor differentiation and the interval between operation and initiation of radiotherapy. For the endpoint of disease-free survival, pelvic lymph node status, tumor differentiation, the duration of interruption of radiotherapy, and the interval between operation and radiotherapy were of independent prognostic significance. As pelvic control was concerned, the 5-year pelvic control rate was 90% and only the duration of interruption of radiotherapy was noted as an independent predictor of pelvic control. Distant metastases were noted in 43 patients (24%); the most common sites were lung (10%), liver (6%), and bone (6%). The overall 5-year intestinal and urinary complication-free rate was 66 and 82%, respectively. The overall incidence of grade 3 or above late rectal and urinary sequelae was 10%. For patients sustaining leg lymphedema after radiotherapy, there was higher incidence of severe leg cellulitis which warranted antibiotics treatment. CONCLUSION: These prognostic factors should be considered in patient counseling and treatment planning. Based on these factors, a more aggressive treatment to improve survival in these subsets of high-risk patients might be justified. New therapeutic regimens and modalities aimed to overcome treatment failure should be investigated.

Adenocarcinoma↗

Microvascular vastus lateralis muscle flap for chronic empyema associated with a large cavity.

Thoracic empyema can be disabling and may need microvascular free flaps in some intractable cases. After repeated failure of conventional thoracic surgical procedures, 2 patients with empyema were treated with microvascular free vastus lateralis muscle flaps for obliteration of the large empyema cavity. The reconstruction was successful in wound closure and eradication of infection. The donor site morbidity was minimal, and the patients resumed normal daily activities. Microvascular vastus lateralis muscle flap is the best option if free flaps are required for reconstruction of empyema.

Aged↗

Microvascular prefabricated free skin flaps for esophageal reconstruction in difficult patients.

BACKGROUND: Reconstruction of the esophagus for complicated benign stricture or after resection of malignant lesion is still a challenge for surgeons. When abdominal viscera cannot be used, skin flaps are selected for esophageal reconstruction. However, skin flaps for esophageal reconstruction are notorious for leakage, and have not been widely accepted. Prefabrication before microvascular transfer to its final site can improve the result of esophageal reconstruction when skin flaps are used. METHODS: Eight patients with complicated corrosive esophagitis had been treated with prefabricated skin flaps for esophageal reconstruction. The procedures are described in detail. RESULTS: All patients healed well without leakage. The barium study showed smooth passage. There was no dysphasia or regurgitation after education. Pulmonary complication happened in only 1 patient. Revision for the distal anastomosis was required in 1 patient due to narrowing. When the skin tube is long, the patients need water (or soup) to facilitate swallowing and occasionally use their hand to help the food passage. This method has the following advantages: (1) healing of the long suture line before transfer to withstand the intestinal juice; (2) reliable viability in the distal part of the flap, especially when an extended length of the flap is required; (3) more length of stable tissue for two-layered, tension-free anastomosis at the junction of skin and gastrointestinal mucosa to prevent leakage; and (4) the flap can be placed in the substernal position to meet the aesthetic requirement of young patients. The disadvantage was the staged operations. However, after prefabrication the transfer becomes safe and free of leakage. The overall morbidity is minimal. CONCLUSIONS: In rare situations when skin flaps are used for esophageal reconstruction, prefabrication provides advantages over conventional one-stage methods, although it needs additional procedures. This method is a combination of conventional technique and microsurgery.

Adult↗

Expression of mu-, kappa- and delta-opioid receptors in P19 mouse embryonal carcinoma cells.

P19 embryonal carcinoma cells are pluripotential and able to differentiate into a variety of cell types, including neurons, glia and fibroblast-like cells, upon retinoic acid treatment and cellular aggregation. Using reverse transcription-polymerase chain reaction, ligand binding and immunocytochemical methods, kappa- and delta-opioid receptors were detected in undifferentiated P19 cells. The mu-opioid receptor was not observed until one day after plating, following one essential step of differentiation, but increased in number in the four days after plating. Several different expression patterns were detected in these differentiated cells. Some cells exhibited mu- and delta-opioid receptors co-expressed, with or without K-opioid receptor; whereas some of the cells expressed only K-opioid receptor. All three opioid receptors are detected on aggregated cells which are postmitotic and also expressing neurofilaments, indicating neuronal characteristics. Furthermore, those cells expressing mu and delta-opioid receptors also expressed glutamate decarboxylase, characteristic of the GABAergic phenotype. Based on these findings, we propose that P19 cells may serve as a model system to study the developmental regulation of opioid receptors, and in particular their relationship with GABA.

Animals↗