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Biomedical subjects

H C Chiu

Publications and source records attributed to H C Chiu.

At least 73 records · Page 4Linked to original sources

Adenovirus-mediated gene therapy of ovarian cancer in a mouse model.

OBJECTIVE: Our purpose was to test the feasibility of adenovirus-mediated gene therapy of ovarian cancer. STUDY DESIGN: Ovarian cancer cell lines were exposed to an adenovirus vector expressing a reporter gene (lacZ) and to the same vector bearing the herpes simplex virus thymidine kinase gene (Ad.RSVtk) followed by ganciclovir. lacZ expression and growth inhibition were quantitated. Immunodeficient mice were injected intraperitoneally and subcutaneously with human ovarian cancer cells and treated with Ad.RSVtk and ganciclovir. Statistical analyses included one-way analysis of variance and t tests. RESULTS: Staining for lacZ demonstrated viral transduction in vitro. After exposure to Ad.RSVtk all cell lines showed significant (p < 0.0001, analysis of variance) cytotoxicity to ganciclovir. Human ovarian tumor cells established subcutaneously or intraperitoneally in immunodeficient mice responded to therapy with Ad.RSVtk followed by ganciclovir. Treated mice had a 10- to 20-fold lower subcutaneous tumor burden than did control mice. Additionally, no intraperitoneal tumors were observed in treated mice. CONCLUSIONS: Ovarian cancer cells are readily transduced with recombinant adenovirus and become sensitive to ganciclovir after transduction with Ad.RSVtk. These data support the development of this method for human clinical trials.

Adenoviridae↗

Silicone cream occlusive dressing--a novel noninvasive regimen in the treatment of keloid.

BACKGROUND: The use of silicone oil in the treatment of hypertrophic scars has recently been much discussed. Silicone gel and silicone cream containing 20% silicone oil have been demonstrated to effectively treat hypertrophic scars. However, the results in treating keloid are variable. OBJECTIVE: The purpose of this study was to evaluate the clinical efficacy of silicone cream with occlusive dressing in the treatment of keloid. METHODS: An open study was performed in 15 Chinese patients with single or multiple keloids. Nineteen keloids were randomly selected and treated with silicone cream occlusive dressing (SCOD). The effectiveness was assessed using a scoring system involving elevation, redness, hardness, itching and tenderness or pain of the lesions. RESULTS: Fifteen out of 19 keloids (79%) showed significant improvement after using SCOD for 6 months. None of the keloids progressed. CONCLUSIONS: We conclude that SCOD is easy to apply, noninvasive, painless, almost free of side effects. It is especially useful in children and those who cannot tolerate the pain or inconvenience of other treatment procedures. The action mechanism of SCOD is still unclear, though hydration and occlusion rather than silicone itself may play an important role.

Adult↗

Human hair follicle dermal papilla cell, dermal sheath cell and interstitial dermal fibroblast characteristics.

The morphologic and functional characteristics of cultured hair follicle dermal papilla (DP) cells, dermal sheath (DS) cells and interstitial dermal fibroblasts (DF cells) derived from human scalp tissue are compared. DP and DS cells, but not DF cells, showed aggregative behavior at a preconfluent density. All three types of cells stained positive for type I collagen, type IV collagen, laminin and heparan sulfate proteoglycan. Only DP and DS cells expressed smooth muscle alpha-actin. DP and DS cells also synthesized more glycosaminoglycans (GAG) than DF cells, while there was no significant difference between DP and DS cells in GAG synthesis. Ultrastructurally, 7 out of 10 strains of DP and 2 out of 10 strains of DS cells were found to form intranuclear rodlets, while none of the 10 strains of DF cells examined formed intranuclear rodlets. The conditioned medium of the three types of cells was collected and tested for the presence of interleukin (IL)-1 beta, tumor necrosis factor (TGF)-beta 2, IL-6, platelet-derived growth factor-AB, epidermal growth factor, b-FGF, GM-CSF, insulin-like growth factor (IGF)-1 and HGF (hepatocyte growth factor) by ELISA or RIA. Among the tested cytokines and growth factors, TGF-beta 2, IL-6 and IGF-I were detectable in at least some conditioned media. The others were undetectable. There was no significant difference in the production of IL-6 and IGF-I among the three types of cells. In contrast, DP cells produced the highest levels of TGF-beta 2, DS cells produced intermediate levels of TGF-beta 2, and DF cells produced the lowest levels of TGF-beta 2. DP and DS cells are morphologically and functionally different from the nonfollicular, interstitial DF cells. Moreover, the presence of some minor biologic differences between DP and DS cells suggests that they represent follicular mesenchymal cells in different functional or differentiation states.

Cell Division↗

Mutation analysis of the BRCA1 gene in ovarian cancers.

Germline mutations of the BRCA1 tumor suppressor gene on chromosome 17q are involved in a significant fraction of hereditary breast and ovarian cancers. Allelic deletions that include the BRCA1 locus are common in breast and ovarian cancers, implying that somatic mutations of this gene may play an important role in the more common sporadic forms of these tumors as well. The recent cloning of BRCA1 allows direct testing of this hypothesis. A combination of single strand conformation and sequencing analyses was used to examine the 22 coding exons and intronic splice donor and acceptor regions of BRCA1 for mutations in 115 unselected cases of epithelial ovarian carcinoma. Seven mutations were identified, all of which were present in the germlines of patients with remarkable family or medical histories of breast and/or ovarian cancer. Eighty-nine of these tumors were examined for loss of heterozygosity in the BRCA1 region of chromosome 17q, and 67% of the tumors studied exhibited allelic deletions that included this region. These data are consistent with the hypothesis that BRCA1 mutations are involved in the etiology of hereditary ovarian carcinomas but occur rarely in sporadic tumors, and that the frequent allelic loss on chromosome 17q in this cancer type reflects the involvement of an additional tumor suppressor gene(s).

Adult↗

Electromechanical effects of caffeine in failing human ventricular myocardium.

We studied, using standard microelectrode technique, the effects of caffeine alone and in conjunction with epinephrine in ventricular myocardial fibers obtained from the failing hearts of 12 recipients of heart transplant. Results revealed that caffeine (1-3 mM) prolonged slightly the duration of fast response action potential near final repolarization and the twitch curve but slightly increased, or even decreased, the twitch force. Epinephrine (3 microM) induced a submaximal positive inotropic effect in myocardial fibers obtained from the failing hearts. Caffeine at 1 mM significantly potentiated the force of contraction and accelerated the rate of twitch relaxation increased by epinephrine. Increasing concentration of caffeine to 3 mM in the presence of epinephrine did not enhance further the twitch force but rather induced the delayed after-depolarization in two of eight experiments. In a preparation from one patient with dilated cardiomyopathy, the combination of caffeine and epinephrine induced repetitive triggered rhythms. The present findings suggest that, in human ventricular myocardium obtained from certain patients transplanted for congestive heart failure, caffeine could induce positive inotropy and triggered automaticity through a potentiation of the actions of catecholamines.

Action Potentials↗

Hydration, not silicone, modulates the effects of keratinocytes on fibroblasts.

Topical silicone gel or silicone cream with occlusive dressing has proved to be an efficacious method for the treatment and prevention of hypertrophic scars and keloids, but how this action is triggered remains unknown. Hydration of the epidermis and/or the cellular effects of the released low-molecular-weight silicone oil have been suggested as possible mechanisms. In order to further elucidate the mechanism, we used an in vitro keratinocyte-fibroblast coculture model to investigate the cellular effects of silicone and hydration. In this model, the condition of clinical usage of topical silicone gel or cream or the condition of hydration exerted by occlusive dressing could be mimicked. The model consisted of two chambers separated by a semipermeable membrane, in which a fully differentiated stratified epithelium is present in the upper chamber and medium and monolayer fibroblasts are located in the lower chamber. The keratinocytes were nourished from the basal side only, while the apical surface was submerged in silicone oil, paraffin, Hanks' balanced salt solution, or medium (hydration); or it was exposed to air (control). In the hydration-treated group, the proliferation of fibroblasts measured as [3H]thymidine incorporation and their collagen, glycosaminoglycan production was significantly inhibited when compared with the controls, but exposure of the keratinocyters to silicone oil or paraffin did not influence fibroblast behavior. The results suggest that hydration, not silicone, modulates the in vitro keratinocyte-fibroblast interaction. This may be one possible mechanism by which topical silicone or occlusive dressing treatment may affect the development of hypertrophic scars and keloids.

Cell Division↗

Subcutaneous fat necrosis of the newborn complicating hypothermic cardiac surgery.

A newborn male infant developed subcutaneous fat necrosis (SCFN) with extensive calcification, 1 week after hypothermic cardiac surgery. The lesions resolved spontaneously, without sequelae, within 10 weeks. Five cases of SCFN occurring after induced hypothermia, used as an adjuvant in cardiac surgery, have been reported to date in the English literature. Our description of a sixth case re-emphasizes hypothermia as one possible cause of SCFN of the newborn.

Fat Necrosis↗

Familial acanthosis nigricans with madarosis.

We report familial acanthosis nigricans affecting a 35-year-old woman, her 7-year-old son and 5-year-old daughter. Absence of the eyebrows and eyelashes was noted in this family. The mother had no axillary hair and her pubic hair was sparse. The boy also suffered from congenital heart disease and a congenital cataract in the left eye. The combination of acanthosis nigricans and ectodermal defects in this family may represent a distinct nosological entity.

Acanthosis Nigricans↗

Atypical mycobacterial cervical lymphadenitis associated with Sweet's syndrome.

We report the case of a 52-year-old woman with a non-tuberculous (atypical) mycobacterial cervical lymphadenitis, caused by Mycobacterium fortuitum, in association with Sweet's syndrome. The cervical lymphadenitis was resistant to medical treatment, and the Sweet's syndrome occurred intermittently. Systemic steroid treatment was required to control the cutaneous symptoms.

Fatal Outcome↗

Effects of estrogen and estrogen receptor in normal human melanocytes.

Normal human melanocytes were cultured selectively with F12 culture medium supplemented with growth hormones, phorbol ester and 1% of fetal calf serum. The estrogen receptors were analyzed using hydroxylapatite-column assay with tritiated 17-beta-estradiol as the binding ligand. Phenol red- free medium was used when the changes in cell numbers, melanin content and tyrosinase were assessed after incubating with physiological concentration of 17-beta estradiol (10(-12) and 10(-9) M). It was found that the melanocytes contained both cytosol (5.42 +/- 1.11 fmol/mg protein) and nuclear (59.13 +/- 17.12 fmol/mg protein) estrogen receptor. In response to estradiol, the cell number increased but both the melanin content and the tyrosinase activity decreased in a dose related pattern. These data suggested the presence of estrogen receptor with biological function in normal human melanocytes.

Animals↗

Increased oxidizability of plasma low density lipoprotein from patients with coronary artery disease.

Oxidative modification of lipoproteins may play a crucial role in the pathogenesis of atherosclerosis. This study was designed to examine whether increased lipid peroxides and/or oxidative susceptibility of plasma lipoproteins occur in patients with coronary artery disease. The levels of lipid peroxides, estimated as thiobarbituric acid-reactive substances (TBARS), were significantly greater in the plasma and very low density lipoprotein (VLDL) of symptomatic patients with coronary artery disease than in those of healthy persons, but the TBARS levels of low density lipoprotein (LDL) and high density lipoprotein (HDL) showed insignificant difference between patients and normals. To evaluate the oxidative susceptibility of lipoproteins, we employed in vitro Cu2+ oxidation of lipoproteins monitored by changes in fluorescence, TBARS level, trinitrobenzene sulfonic acid (TNBS) reactivity, apolipoprotein immunoreactivity and agarose gel electrophoretic mobility. While pooled VLDL and LDL of normal controls were oxidized at 5-10 microM Cu2+, pooled VLDL and LDL of patients with coronary artery disease were oxidized at 1-2.5 microM Cu2+, i.e., at relatively lower oxidative stress. At 5 microM Cu2+, VLDL and LDL of patients with coronary artery disease still showed a faster oxidation rate, judged by the rate of fluorescence increase, higher TBARS level, less TNBS reactivity, greater change in apo B immunoreactivity and higher electrophoretic mobility than those of normal controls. However, the difference on the oxidizability of HDL was insignificant for patients vs. normals. In conclusion, we have shown that plasma VLDL and LDL of patients with coronary artery disease are more susceptible to in vitro oxidative modification than those of healthy persons. The data suggest that enhanced oxidizability of plasma lipoproteins may be an important factor influencing the development of coronary artery disease.

Adult↗

Plasma protein C activity is enhanced by arsenic but inhibited by fluorescent humic acid associated with blackfoot disease.

Blackfoot disease is a peripheral vascular disease causally related to the fluorescent humic acid found in the drinking water of endemic areas in Taiwan. We compared the effects of humic acid (HA) purified from the well water of Blackfoot disease endemic areas with the effects of commercial humic acid (Aldrich) as well as trivalent arsenic (As2O3) on protein C activity, which plays an important role in regulation of blood coagulation and fibrinolysis. Humic acid, either purified from drinking water or obtained commercially, dose-dependently inhibited both activated protein C activity and the activation of protein C induced by Protac, a snake venom-derived protein C activator. In contrast to humic acid, arsenic oxide dose-dependently enhanced both activated protein C activity and the Protac-stimulated activation of protein C. In the presence of humic acid the enhancement effect of arsenic oxide was completely abolished, resulting in concentration-dependent inhibition of protein C activity. Therefore, the results of this study indicate that humic acid is a potent protein C inhibitor even in the presence of arsenic, which enhances the protein C activity. Since protein C is a potent anticoagulant and profibrinolytic agent, acquired defects of protein C induced by humic acid might cause a thrombophilic or hypercoagulable state. Whether this is one of the possible mechanisms of humic acid-induced thrombotic disorders in Blackfoot disease needs to be further characterized.

Arsenic↗

Human dermal papilla cells and outer root sheath cells: no follicular differentiation in nude mice and chicken embryos.

Human scalp specimens were incubated in 5 U/ml dispase solution at 4 degrees C overnight before the isolation of dermal papillae and follicle epithelium. This pretreatment not only facilitated the attachment and cell outgrowth of dermal papillae but also made it easier to pluck out hairs with intact follicle epithelium. The outer root sheath cells were released from the follicle epithelium and grown on a feeder layer of mitomycin C-treated human dermal fibroblasts. The subcultured outer root sheath cells were grown in a serum-free medium. When the mixtures of early-passage dermal papilla cells and outer root sheath cells were injected into the subcutis of nude mice, an epidermal cyst surrounded by layers of fibrous tissue was found in three weeks. No hair follicles were found when the mixtures were implanted onto the chorioallantoic membrane of nine-day-old chicken embryos. A keratinized mass lying on the chorionic epithelium with or without smaller similar masses in the chorioallantoic membrane was found in eight days. No hair follicle-like structure could be found. Possible factors contributing to the failure to undergo follicular differentiation in this study are discussed.

Animals↗