Biomedical subjects

Y S Ho

Publications and source records attributed to Y S Ho.

At least 73 records · Page 4Linked to original sources

PubMed1998

Clinical and pathological characteristics of secondary thyroid cancer.

Although up to 24% of metastatic cancers have been reported to spread to the thyroid gland, metastases to the thyroid are not detected in clinical practice in most cases. The prognosis is poor when metastatic cancer to the thyroid occurs. The aim of this study was to examine the clinical presentation, cytopathological findings, and clinical course of secondary cancers of the thyroid. The medical records of a total of 1013 histopathologically verified thyroid cancer patients treated during the period from January 1977 to December 1995 in Chang Gung Medical Center in Linkou were analyzed retrospectively. There were 14 patients (1.4% of all thyroid cancers) with secondary cancers of the thyroid with a mean age of 55.3 +/- 16.7 years. All these patients underwent thyroid ultrasonography and a fine-needle aspiration cytology of the thyroid (FNAC) before biopsy or surgical treatment. Tissue diagnosis was obtained by biopsy or necropsy in 12 or by thyroidectomy specimens in 2 patients. Most of the patients died within 9 months of diagnosis except for 2 patients who were lost to follow-up after transferring to another hospital and 1 patient with lymphoma. Before the surgical diagnosis, there were only 7 patients who metastatic neoplasms to the thyroid gland were diagnosed by FNAC. Anaplastic thyroid carcinoma was diagnosed in 5 patients. Benign nodule was diagnosed in 1 patient and lymphoma in another patient. Most of these patients had widespread metastases to many organs, as well as the thyroid gland. As a result these patients had very short survival times. Delayed diagnosis of the thyroid metastasis was the main reason for the short survival period. In conclusion, most of the metastatic lesions presented as an advanced stage of primary cancers. FNAC was a useful tool in the diagnosis. Histopathological diagnosis by surgical open biopsy is needed for the final diagnosis.

Adult↗

PubMed1998

Cellular glutathione peroxidase is the mediator of body selenium to protect against paraquat lethality in transgenic mice.

The antioxidative role of Se-dependent cellular glutathione peroxidase (EC 1.11.1.9, GPX1) in vivo has not been established. Our objective was to determine the effects of GPX1 knockout or overexpression on the susceptibility of mice to paraquat toxicity and the contributions of GPX1, compared with other selenoproteins and vitamin E, to body defenses against such acute oxidative stress. Four experiments were conducted using 111 GPX1 knockout or overexpressing mice and the respective controls. Mice were fed diets supplemented with Se (as sodium selenite) at 0-0.4 mg/kg and/or all-rac-alpha-tocopheryl acetate at 0-75 mg/kg before intraperitoneal injections of 12.5, 50 or 125 mg paraquat/kg body weight. All mice that received 50 or 125 mg paraquat/kg died spontaneously, and the survival time of mice was (independent of dietary levels of Se per se or alpha-tocopheryl acetate) solely a function of tissue GPX1 activity (P < 0.001). Severe acute pulmonary interstitial necrosis was found only in the GPX1 overexpressing mice and the controls that had extended survival time. Thiobarbituric acid reacting substances in postmortem liver inversely correlated with the tissue GPX1 activity and dietary levels of Se and/or alpha-tocopheryl acetate. In contrast, all mice that received 12.5 mg paraquat/kg survived and were killed 2 wk after the injection for tissue collection. Compared with the saline injection, this low dose of paraquat resulted in greater (P < 0.001) liver and lung F2-isoprostanes in both the GPX1 knockout mice and the controls. However, there was no difference in plasma alanine transaminase (EC 2.6.1.2) activity or overt injuries in liver, lung and kidney in either group. Our data indicate that GPX1 is the major, if not the only, metabolic form of body Se that protects mice against the lethal oxidative stress caused by high levels of paraquat; it seems less important, however, in protecting mice against the moderate oxidative stress by the low level of paraquat.

Animals↗

PubMed1998

Glutathione peroxidase protects mice from viral-induced myocarditis.

Glutathione peroxidase 1 (GPX-1) is a selenium-dependent enzyme with antioxidant properties. Previous investigations determined that mice deficient in selenium developed myocarditis when infected with a benign strain of coxsackievirus B3 (CVB3/0). To determine whether this effect was mediated by GPX-1, mice with a disrupted Gpx1 gene (Gpx1-/-) were infected with CVB3/0. Gpx1-/- mice developed myocarditis after CVB3/0 infection, whereas infected wild-type mice (Gpx1+/+) were resistant. Sequencing of viruses recovered from Gpx1(-/-)-infected mice demonstrated seven nucleotide changes in the viral genome, of which three occurred at the G residue, the most easily oxidized base. No changes were found in virus isolated from Gpx1+/+ mice. These results demonstrate that GPX-1 provides protection against viral-induced damage in vivo due to mutations in the viral genome of a benign virus.

Animals↗

PubMed1998

Experience with laser hair transplantation in Orientals.

BACKGROUND: The advent of high-energy carbon dioxide (CO2) laser-assisted hair transplantation in recent years provides a new recipient area technique for hair restoration surgery. It offers the advantages of less bleeding, time consumption, and graft compression. Specific laser parameters have been recommended in Caucasian but not Oriental patients. OBJECTIVE: To determine the effectiveness as well as appropriate parameters of laser hair transplantation in Oriental patients. METHODS: A Sharplan SilkTouch laser with the Flashscanner set to produce a 0.8-1-mm recipient site hole was employed for all subjects. Various CO2 laser parameters were used to compare the graft survival rate with traditional Nokor needle or microdilator methods for micrografting on each side of the scalp. A total of 20 patients joined the study in the past 18 months. A skin biopsy was performed to examine the tissue effect of the different laser parameters. RESULTS: Hair survival was less than that seen with conventional micrografting techniques in the first five cases, in whom CO2 laser parameters of 36-40 W and 0.2-0.7 seconds were used. After adjusting the parameters to 55 W and 0.1-0.15 seconds, the survival rate increased to between 80% and 90%. In addition, most patients thought the laser-prepared sites resulted in a more natural appearance and better hair density, when they were compared with conventionally prepared sites. CONCLUSIONS: From our study, we find that CO2 laser parameters of 55 W and 0.1-0.15 seconds seem to be the appropriate parameters for Oriental hair transplant patients. Further studies are required to establish laser parameters that will produce better hair survival.

Alopecia↗

PubMed1998

Involvement of immunopathogenic mechanisms in a spontaneously occurring glomerulopathy in mice.

Mice have been found to be susceptible to spontaneous renal localization of immune deposits. However, the significance of these immune deposits is still debated. We investigated the immunopathogenesis of a naturally occurring glomerulopathy associated with progressive proteinuria and glomerulosclerosis in 75 BALB/c mice. The mice were divided into five groups of 15 and killed at the age of 1, 3, 6, 12, or 18 months for laboratory and renal pathologic studies. These mice showed persistently increasing serum levels of immune complexes, a marked increase of glomerular immune deposits which were capable of fixing C3, and interstitial infiltration of lymphocytes and plasma cells, followed by the occurrence of proteinuria, mesangiopathy, and glomerulosclerosis. Our findings suggest that an immune system mediated process occurred in the kidneys of the mice tested.

Animals↗

PubMed1998

Experimental focal segmental glomerulosclerosis in mice.

Although a lot of animal models of proteinuria have been established, proposals for the mechanisms of proteinuria are still controversial. In this work, during an 18-day trial, mice injected with a single dose of adriamycin (AD) rapidly showed combined glomerular albuminuria and immunoglobulinuria, progressively elevated levels of nitrite/nitrate in urine, hypercholesterolemia, abnormal renal function, segmentally or globally glomerular hyalinosis/sclerosis associated with tubular atrophy, enhanced glomerular deposition of immunoglobulins and fibrinogen, augmented expression of matrix components in the whole glomerular tuft, and loss of glomerular negative charge property. These laboratory and pathological features are comparatively similar to those of human focal segmental glomerulosclerosis in the advanced state. Juxtamedullary glomeruli appear to be more susceptible to the AD-related nephrotoxicity than those in the superficial renal cortex. A change in size-dependent glomerular permselectivity may precede a charge-dependent defect in glomeruli in this mouse model of proteinuria. Data in this study confirm the hypothesis of glomerular hyperfiltration involved in the pathogenesis of this chronic glomerulopathy associated with proteinuria in mice. In addition, nitric oxide may play a crucial role in the progression of the chronic glomerulopathy model.

Animals↗

PubMed1998

Transgenic models for the study of lung antioxidant defense: enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia.

To investigate the role of manganese-containing superoxide dismutase (MnSOD) in lung antioxidant defense, lines of transgenic B6C3 hybrid mice carrying human MnSOD transgenes under the transcriptional control of a human beta-actin promoter were established. Expression studies demonstrated that the human MnSOD transgene in line TgHMS66 is expressed and functional. The cellular distribution of the transgene product in the lungs was further examined by immunocytochemical analysis. Increased immunoreactive MnSOD was found in mitochondria of lung type I epithelial cells, type II epithelial cells, capillary endothelial cells, and fibroblasts. Furthermore, the magnitude of increase in mitochondrial labeling density of type II cells of nontransgenic, hemizygous, and homozygous transgenic littermates was proportional to the increased lung activity of MnSOD found in these mice. Transgenic mice over-expressing MnSOD did not have enhanced survival relative to controls when exposed to > 99% oxygen. However, when exposed to 90% oxygen, the transgenic mice had a small but statistically significant increase in survival time. Our results indicate that when the beta-actin promoter is used to increase activity of MnSOD it provides modest protection to B6C3 mice against hyperoxic lung injury.

Animals↗

PubMed1998

Cervical ecchordosis physaliphora: CT and MR features.

We report a case of cervical ecchordosis physaliphora in an elderly man who presented with hemihypoaesthesia and contralateral hemiparesis. MRI showed a well defined, non-enhancing extradural mass lesion on the dorsal surface of the odontoid process of the axis. The lesion was of intermediate signal intensity on T1 weighted images and of low signal intensity on T2 weighted images. CT showed a small bony defect on the adjacent cortex of the odontoid process. Recognition of the imaging features of ecchordosis physaliphora is helpful in suggesting the diagnosis and differentiating the lesion from chordoma.

Aged↗

PubMed1998

The nature of antioxidant defense mechanisms: a lesson from transgenic studies.

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury.

Animals↗

PubMed1998

Preoperative embolization of meningiomas: comparison of superselective and subselective techniques.

We retrospectively compared the efficacy of preoperative superselective and subselective embolization for intracranial meningiomas. Between January and December 1996, 22 patients (7 men, 15 women, mean age 51 +/- 15.5 yr) underwent superselective embolization with 45 to 150 mm polyvinyl alcohol particles after superselective catheterization of the feeding vessels with a microcatheter system. Another 30 patients (12 men, 18 women, mean age 50 +/- 12.9 yr) underwent subselective embolization between January and December 1995 with 150 to 300 mm Gelfoam particles after catheterization of the terminal external carotid artery just proximal to the orifice of the maxillary artery with a 4- or 5-F angiocatheter. The mean intraoperative blood loss (918 versus 1450 mL, p < 0.05), amount of blood transfused (4.9 versus 7.5 units, p = 0.09), and surgical resection time (422 versus 529 min, p < 0.05) were all lower in the superselective group than in the subselective group, while the occurrence of fresh ischemic necrosis (59% versus 53%, p = 0.68), hemorrhage (77% versus 60%, p = 0.19), and embolic material (55% versus 13%, p < 0.05) on pathologic examination were higher in the superselective group. No procedure-related complications occurred in the superselective group, whereas two patients in the subselective group had postoperative scalp necrosis. Our findings show that superselective embolization is more effective than subselective embolization for preoperative endovascular devascularization of meningiomas, with significant reductions in intraoperative blood loss and surgery time. Preoperative embolization of meningiomas, if indicated, should be done with the superselective technique whenever feasible.

Adult↗

PubMed1998

Lhermitte-Duclos disease: first report in Taiwan.

We report a case of Lhermitte-Duclos disease (dysplastic gangliocytoma of the cerebellum), an uncommon disorder of uncertain pathogenesis characterized by disarrangement of the normal cerebellar laminar cytoarchitecture. A 40-year-old man was admitted because of vomiting and syncope of a few days' duration, and a 2-month history of intermittent headaches and unsteady gait. A computed tomographic scan of the patient's head showed obstructive hydrocephalus due to displacement of the fourth ventricle by a large, nonenhancing cerebellar mass. The magnetic resonance images of the brain also revealed a space-occupying lesion within the right cerebellum with unusual septation. After surgery, the histologic examination confirmed the diagnosis of Lhermitte-Duclos disease. This is the first report of Lhermitte-Duclos disease in Taiwan.

Adult↗

PubMed1997

Glutathione peroxidase knockout mice are susceptible to myocardial ischemia reperfusion injury.

BACKGROUND: To test our hypothesis that intracellular antioxidant enzymes constitute a cellular defense against acute stress, we studied myocardial ischemia reperfusion injury in the setting of reduced level of glutathione peroxidase using GSHPx-1 gene knockout mice. METHODS: Knockout mice were developed by disrupting the coding sequence of GSHPx-1 gene after inserting a neomycin resistance gene derived from pMCIpol A into the EcoRI site located in exon 2. Isolated perfused hearts were prepared from two groups of mice-knockout and nontransgenic controls. A 4-0 silk was attached to the apex of the heart which in turn was attached to a force transducer. Hearts were perfused by the Langendorff mode, and after 20 minutes of stabilization subjected to 30 minutes of ischemia followed by 2 hours of reperfusion. The force developed by the heart (DF) and the first derivative of DF (dF/dt) were recorded. Creatine kinase (CK) release was measured in the perfusate and the infarct size was measured at the end of each experiment. RESULTS: For both GSHPx-1 knockout and nontransgenic control groups, DF and dF/dt were significantly lower during early postischemic reperfusion compared with baseline, but these values were significantly higher for the control group than the knockout mice throughout most of the reperfusion period. CK release from the heart increased during reperfusion for both groups, but this increase was significantly lower for the control group. The infarct size was also smaller for the control mice as compared with knockouts. CONCLUSIONS: The results indicate that the knockout mice are more susceptible to ischemia reperfusion injury, suggesting the importance of GSHPx-1 gene in myocardial protection from ischemic reperfusion injury.

Animals↗

PubMed1997

Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia.

Glutathione peroxidase, a selenium-containing enzyme, is believed to protect cells from the toxicity of hydroperoxides. The physiological role of this enzyme has previously been implicated mainly using animals fed with a selenium-deficient diet. Although selenium deficiency also affects the activity of several other cellular selenium-containing enzymes, a dramatic decrease of glutathione peroxidase activity has been postulated to play a role in the pathogenesis of a number of diseases, particularly those whose progression is associated with an overproduction of reactive oxygen species, found in selenium-deficient animals. To further clarify the physiological relevance of this enzyme, a model of mice deficient in cellular glutathione peroxidase (GSHPx-1), the major isoform of glutathione peroxidase ubiquitously expressed in all types of cells, was generated by gene-targeting technology. Mice deficient in this enzyme were apparently healthy and fertile and showed no increased sensitivity to hyperoxia. Their tissues exhibited neither a retarded rate in consuming extracellular hydrogen peroxide nor an increased content of protein carbonyl groups and lipid peroxidation compared with those of wild-type mice. However, platelets from GSHPx-1-deficient mice incubated with arachidonic acid generated less 12-hydroxyeicosatetraenoic acid and more polar products relative to control platelets at a higher concentration of arachidonic acid, presumably reflecting a decreased ability to reduce the 12-hydroperoxyeicosatetraenoic acid intermediate. These results suggest that the contribution of GSHPx-1 to the cellular antioxidant mechanism under normal animal development and physiological conditions and to the pulmonary defense against hyperoxic insult is very limited. Nevertheless, the potential antioxidant role of this enzyme in protecting cells and animals against the pathogenic effect of reactive oxygen species in other disorders remains to be defined. The knockout mouse model described in this report will also provide a new tool for future study to distinguish the physiological role of this enzyme from other selenium-containing proteins in mammals under normal and disease states.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1997

Induction of glutathione depletion, p53 protein accumulation and cellular transformation by tetrachlorohydroquinone, a toxic metabolite of pentachlorophenol.

Glutathione (GSH) conjugate formation with tetrachlorohydroquione (TCHQ) and the GSH content in vivo were measured by capillary zone electrophoresis. A more than 60% depletion of GSH content was found in liver tissue of mice treated with TCHQ. In addition, p53 protein accumulation and DNA fragmentation was induced by TCHQ. A two-stage model of chemical transformation of mouse embryonic fibroblasts was used to elucidate the transformation activity of TCHQ in vitro, and a 33% foci formation efficiency was found at the concentration of 5 microM. GSH depletion caused by TCHQ could abolish the protective ability of the cell against reactive oxygen species provided by GSH. When DNA was damaged, p53 protein accumulated in the nucleus and, in the case of severe damage, initiated apoptosis. TCHQ's ability to cause GSH depletion and DNA damage may play a role in the cytotoxic and genotoxic properties of its metabolic precursor, PCP.

3T3 Cells↗

PubMed1997

The Gpx1 gene encodes mitochondrial glutathione peroxidase in the mouse liver.

Mitochondria have GPX and PHGPX activity. It has been an unsettled issue whether mitochondrial GPX is encoded by Gpx1. Unlike the Gpx4 gene which encodes PHGPX with alternative transcription and translation start sites determining the subcellular localization of PHGPX, the Gpx1 gene appears to have a single translation start site. Additionally, mitochondrial GPX has been shown to have different chromatographic and kinetic properties from the cytosolic GPX1. We studied mouse liver mitochondrial GPX activity in homozygous Gpx1-knockout mice. Mitochondria were enriched at the density of 1.10 g/ml in the Percoll gradients as shown by electron microscopy. The H2O2-reducing GPX activity in the highly enriched mitochondrial fraction of wild-type mouse liver is 2700 mU/mg which is about one-half of specific activity found in cytosol. There is less than 0.5% GPX activity in the cytosol and no GPX activity in the mitochondria of Gpx1-knockout mouse liver compared to the cytosol of wild-type mouse liver using H2O2 or cumene hydroperoxide as the substrate. The fact that the knockout mice express normal levels of plasma GPX as well as testis and liver PHGPX activity indicates that animals are not selenium-deficient. Based on these observations, we concluded that mitochondrial GPX is the product of the Gpx1 gene.

Animals↗

PubMed1997

Brain acetylhydrolase that inactivates platelet-activating factor is a G-protein-like trimer.

The platelet-activating factor PAF (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent lipid first messenger active in general cell activation, fertilization, inflammatory and allergic reactions, asthma, HIV pathogenesis, carcinogenesis, and apoptosis. There is substantial evidence that PAF is involved in intracellular signalling, but the pathways are poorly understood. Inactivation of PAF is carried out by specific intra- and extracellular acetylhydrolases (PAF-AHs), a subfamily of phospholipases A2 that remove the sn-2 acetyl group. Mammalian brain contains at least three intracellular isoforms, of which PAF-AH(Ib) is the best characterized. This isoform contains a heterodimer of two homologous catalytic subunits alpha1 and alpha2, each of relative molecular mass 26K, and a non-catalytic 45K beta-subunit, a homologue of the beta-subunit of trimeric G proteins. We now report the crystal structure of the bovine alpha1 subunit of PAF-AH(Ib) at 1.7 A resolution in complex with a reaction product, acetate. The tertiary fold of this protein is closely reminiscent of that found in p21(ras) and other GTPases. The active site is made up of a trypsin-like triad of Ser 47, His 195 and Asp 192. Thus, the intact PAF-AH(Ib) molecule is an unusual G-protein-like (alpha1/alpha2)beta trimer.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1997

The contribution of GSH peroxidase-1, catalase and GSH to the degradation of H2O2 by the mouse lens.

Utilizing cultured lenses from normal and homozygous glutathione peroxidase (GSHPx-1) knockout mice and inhibitors for GSSG Reductase (GSSG Red), 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) and catalase (Cat), 3-aminotriazole (3-AT), the ability to degrade H2O2 was examined at two H2O2 concentrations, 300 microM and 80 microM. It was found that GSHPx-1 contributed about 15% to the H2O2 degradation. The Cat contribution was concentration dependent being about 30% at 300 microM H2O2 and approximately 8% to 15% at 80 microM H2O2. GSH loss measured as nonprotein thiol (NP-SH) was shown to be linked to most of the remaining H2O2 degradation accounting for about 54% to 72% of the H2O2 degradation at 300 microM and 80 microM, respectively. However, based on evaluation of the ability of GSH to nonenzymatically degrade H2O2, it can only account for about 36% at 300 microM and 19% at 80 microM H2O2 of the observed lens H2O2 degradation. It is, therefore, concluded that lens GSH must be involved in other reactions either directly or indirectly related to H2O2 degradation.

Amitrole↗

PubMed1997

Pathogenetic implications of DNA nondiploidy in colorectal cancers.

PURPOSE: Several studies propose that proximal and distal colorectal cancers have a different pathogenesis. We tested the hypothesis using flow cytometric DNA analysis. METHODS: DNA analysis was performed in 719 patients with colorectal cancer. In addition, histopathologic data were re-evaluated in a blinded fashion by a single pathologist. RESULTS: Distal tumors were more often nondiploid than were proximal tumors (61 vs. 49 percent; P = 0.015). Compared with the proximal tumor, distal tumors were smaller (P = 0.0001) and had less desmoplastic reaction (39 vs. 53 percent; P = 0.0001). Tumor location had no significant associations with the remaining parameters, including mucin production, perineural invasion, blood/lymphatic vessel invasion, lymphocytic infiltration, histologic grade, tumor stage, gross appearance, age, and gender. CONCLUSIONS: The unequal distribution of ploidy suggests distinct pathogenetic mechanisms at proximal and distal sites.

Colorectal Neoplasms↗