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Biomedical subjects

Y S Ho

Publications and source records attributed to Y S Ho.

At least 127 records · Page 7Linked to original sources

Effects of hypoxia on MnSOD expression in mouse lung.

Mitochondrial manganese-containing SOD (MnSOD) is located at the primary site of O2 metabolism, and its expression may be regulated by changes in O2 level. We hypothesized that lung MnSOD expression and promoter activity would decrease in response to hypoxia. We tested effects of hypoxia (10% O2 at sea level for 7 days) on chloramphenicol acetyltransferase (CAT) reporter and MnSOD gene expression in transgenic mice. The transgene consisted of a 3.3-kb portion of the rat MnSOD gene 5' flanking region coupled to a CAT reporter gene. Lung MnSOD activity in male (but not female) mice decreased significantly after hypoxia exposure. The decrease in MnSOD enzymatic activity in male mice was specific. Neither total SOD nor glucose-6-phosphate dehydrogenase (G-6-PDH) activity decreased significantly in hypoxia. CAT protein expression decreased in transgenic males exposed to hypoxia, while CAT protein expression in hypoxic transgenic females remained comparable with controls. The mRNA for both the native MnSOD and the MnSOD-CAT reporter genes remained constant after hypoxia, as did CuZnSOD and G-6-PDH mRNAs.

Animals↗

Hairy cell leukemia variant.

A 59-year-old man presented with lymphocytosis with huge splenomegaly. The abnormal lymphocytes had a high nucleoplasm:cytoplasm ratio, a prominent nucleolus and hairy cytoplasmic projections. Immunophenotyping revealed B-cell leukemia with negative reactions to CD5 and CD25. Cytogenetic study showed 46,XY,der(5)t(5;6)(q35;p21), del(7)(p13)/46,idem,add(22)(q13). The patient did not respond to chlorambucil and a combination of cyclophosphamide, vincristine and prednisolone. Splenic irradiation induced partial remission. He developed progressive anemia and thrombocytopenia and died of Escherichia coli septicemia 33 months after the diagnosis of hairy cell leukemia variant.

Fatal Outcome↗

Survival impact of lymph node metastasis in TNM stage III carcinoma of the colon and rectum.

BACKGROUND: Node-positive (TNM stage III) adenocarcinoma of the colon and rectum consists of tumors with a widely variable prognosis. To predict the outcome of patients with stage III carcinoma, we assessed the survival impact of the number and level of lymph node metastasis and other clinicopathological variables. STUDY DESIGN: A retrospective study was performed on 538 patients with stage III carcinoma of the colon and rectum who underwent curative resection at Chang Gung Memorial Hospital between 1980 and 1989. Ten or more lymph nodes in each resected specimen were identified microscopically. Multivariate analysis was used to determine the independent variables. RESULTS: The relative survival rates at five and ten years were 52 and 42 percent, respectively. Tumor morphology, depth or tumor penetration, histologic grade, and the status (number and level) of nodal involvement were significant in the univariate analyses. Only grade and nodal status remained significant in the multivariate analysis. Based on the nodal status, these patients were separated into three groups: stage IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more nodes or presence of pN3). The five-year survival rates for patients with stages IIIA, IIIB, and IIIC disease were 69, 44, and 29 percent, respectively. Compared with patients with stage IIIA disease, the odds of death for patients with stages IIIB and IIIC carcinoma were 2.1 (95 percent confidence interval: 1.5 to 2.8, p = 0.0001) and 3.3 (95 percent confidence interval 2.4 to 4.5, p = 0.001), respectively. CONCLUSIONS: We suggest that stage III adenocarcinoma of the colon and rectum be divided into three substages: IIIA (one to three positive nodes and absence of pN3 metastasis), IIIB (four to nine nodes and absence of pN3), and IIIC (ten or more positive nodes or presence of pN3.

Adenocarcinoma↗

Endometriosis in adolescent women.

With the aim of determining an effective therapy for adolescent women with endometriosis, the authors analyzed the results of laparotomy performed on 16 cases of female teenagers over a seven-year period. All patients, whose average age of menarche is 12.8, were diagnosed with endometriosis between two months and nine years after the menarche, with an average interval of 5.2 years. The chief symptoms are dysmenorrhea, pelvic pain and abdominal fullness. Of the three patients of unicornuate uterus with rudimentary horn, endometriosis was found only involving the adnexa on the side of the rudimentary horn, two of the three patients had absence of affected side kidney. Conservative operation including six cases of salpingo-oophorectomy and 10 cases of ovarian cystectomy were chosen followed by danazol treatment. One year to seven years after surgical treatment, two patients required subsequent conservative operation for recurrence of endometriosis and two other patients resumed dysmenorrhea. Two married women became pregnant 5 and 10 months after surgical and medical therapy respectively. In conclusion, adolescent endometriosis may occur around five years after menarche and an obstructive uterine anomaly, enhancing retrograde menstruation, increases the occurrence rate. The symptoms and treatment of endometriosis in teenage group do not really differ from that in the older women. In the treatment of endometriosis and for the prevention of recurrence, it is recommended to give three to six months of danazol after surgical treatment.

Adolescent↗

p53 gene mutations in brain tumors in Taiwan.

Mutations of the p53 gene were investigated in 116 surgically removed primary brain tumor tissues by PCR-SSCP analysis. The mutations did not follow a random distribution among the various different subtypes, but occurred in 21.0% (13/62) of astrocytomas, 13.0% (3/23) of oligodendrogliomas and 35% (7/20) 35% (7/20) of PNETs. No mutation was found in the ependymomas. The majority of mutations identified in this study were G:C to A:T or C:G to T:A transitions (56.0%, 14 of 25) and occurred most frequently (56.0%, 14 of 25) at sites of CpG dinucleotides. Interestingly, codon 158 is a new hot spot which occurred with a frequency of 16.0% (4 of 25) in the samples analyzed.

Base Sequence↗

Nasopharyngeal carcinoma with brain metastasis: a case report.

We report a case of nasopharyngeal carcinoma with brain metastasis of a 69-year-old man. The patient presented with blindness and a huge mass over right upper neck. The magnetic resonance imaging (MRI) showed right nasopharyngeal tumor and metastatic lesion in bilateral occipital regions. The bony x-ray showed diffuse osteoblastic metastases. The brain lesion was pathology-proven through the computed-tomographic guidance stereotactic biopsy.

Aged↗

Intraventricular haemorrhage and hydrocephalus caused by intraventricular parasitic granuloma suggesting cerebral sparganosis.

A 67-year-old female farmer presented with acute loss of consciousness. Computed tomograms showed a calcified mass in the cavum septi pellucidi with intraventricular haemorrhage and obstructive hydrocephalus. The patient became fully conscious after urgent external ventriculostomy and subsequently underwent craniotomy for the excision of the mass. Pathological examination of the mass demonstrated a granuloma surrounding a degenerating larva compatible with Spirometra mansonoides whose mimicking an intraventricular tumour has not been reported before.

Aged↗

Flavonoid-induced acute nephropathy.

We report two cases of acute renal failure induced by sciadopitysin, a type of flavonoid, and review related papers of flavonoid-induced acute nephropathy in the literature. A total of eight patients were studied. The purpose of this report is to alert physicians to consider this cause of acute renal failure with hemolysis, because flavonoids are widely used in the world. All patients initially presented with fever and gastrointestinal upset after the ingestion of a single large dose or long-term small doses. Symptoms that followed were cola-colored urine and jaundice. Elevation of blood nitrogen and serum creatinine lasted for 2 to 9 weeks. Hemolysis (100%), cholestatic hepatitis (50%), and disseminated intravascular coagulopathy (50%) were also noted in flavonoid-induced oliguric acute renal failure patients. All of these patients required hemodialysis and all but one who died completely recovered within 2 to 9 weeks. Renal biopsy was performed and showed acute interstitial nephritis with acute tubular necrosis. Moreover, we first demonstrated multiple polymorphous inclusion bodies within tubular epithelial cells in electron microscopic examinations. The definite pathogenetic mechanism of flavonoid-induced acute nephropathy needs further elucidation.

Acute Kidney Injury↗

N-nitroso-2-acetylaminofluorene: a direct-acting carcinogen inducing hepatocellular carcinoma in Sprague-Dawley rats.

To compare the hepatotoxicity and hepatocarcinogenicity of N-nitroso-2-acetylaminofluorene (NO-AAF) and its parent compound, 2-acetylaminofluorene (AAF), male Sprague-Dawley rats were given intraperitoneal (i.p.) or subcutaneous (s.c.) injections of AAF or NO-AAF (60 mg/kg body weight/week) for ten months. In the AAF group, morphological changes were produced which involved gross distortions of the liver with multiple nodule formations. The rat livers in the NO-AAF group appeared to be smooth with a blunt-thick superior segment of the lateral lobe. The serum gamma-glutamyl transpeptidase activity in both the AAF group and the NO-AAF group was significantly elevated (P < 0.0005). The present study shows that i.p. and s.c. injections of NO-AAF resulted in a high incidence of well-differentiated hepatocellular carcinomas (HCC) (7/9 and 4/6, respectively), while poorly differentiated HCCs were induced by i.p. or s.c. administration of AAF (6/9 or 2/6, respectively). Subcutaneous lesions consisting of an inflammatory reaction and fibroadenoma formation were observed in the NO-AAF-treated rats, whereas no such skin lesions were detected in the AAF-treated animals. These results suggest that NO-AAF is a new direct-acting carcinogen which may be useful for investigating hepatocarcinogenesis.

2-Acetylaminofluorene↗

Transgenic models for the study of lung biology and disease.

Transgenic models provide a means of understanding the molecular mechanisms for the temporal, spatial, and stimulus-responsive regulation of gene expression in vivo and importantly the pathophysiological consequences of the altered expression of a normal or mutated gene. To facilitate the application of transgenic models in lung research, this review describes several practical considerations in generation of transgenic mice. The potential of transgenic models in lung research is also illustrated by depicting the current models in lung research including those for understanding lung gene regulation, tumorigenesis, mutation detection, antioxidant defense, emphysema, fibrosis, and hypertension. The impact of important new development of producing transgenic mice carrying large fragments of DNA contained in yeast artificial chromosomes to achieve proper control of transgene expression and gene targeting technology is also discussed. It is anticipated that transgenic models will provide invaluable information in future lung research.

Animals↗

Alveolar soft part sarcoma of the vagina. A case report.

We present a case of alveolar soft part sarcoma of the vagina in an 18-year-old woman. The presenting symptoms were menometrorrhagia and a painless vaginal mass. The tumor was in the vaginal stroma with intact mucosa. Periodic acid-Schiff stain showed positive diastase-resistant crystals in some of the tumor cells. Electron microscopy demonstrated characteristic intracytoplasmic crystals. Formaldehyde-induced fluorescence stain showed no catecholamines, and Grimelius stain showed no argyrophilic granules. Black pigment was found within some tumor cells; it proved to be melanin pigment by Masson-Fontana stain. The tumor mass recurred four months after local excision. Following the second surgical removal, the patient received adjuvant radiotherapy to the whole pelvis, including the vagina. At this writing she was currently alive, without evidence of recurrence, five years after the primary diagnosis.

Adolescent↗

The effects of fibroblasts on the growth and differentiation of human bulbar conjunctival epithelial cells in an in vitro conjunctival equivalent.

PURPOSE: To study the effects of collagen matrix and fibroblasts on the growth and development of human bulbar conjunctival epithelial cells. METHOD: Human bulbar conjunctival epithelial cells were cultured on three-dimensional collagen gels containing either normal human conjunctival fibroblasts (HCF), Swiss 3T3 cells, or no cells. After 1 week of culturing, half of the cultures were raised to the air-liquid interface and the rest of the cultures remained submerged. On day 14, cultures were fixed and sectioned for light and electron microscopic studies. RESULTS: Conjunctival epithelial cells cultured on fibroblast-contracted collagen lattice developed into a multicell-layer epithelium with characteristic epithelial structural features including microvilli, desmosomes, early hemidesmosomes, and basement membrane-like structures. Formation of all or some of the above features appeared to be influenced by the type of fibroblasts in the collagen lattices. Structures such as hemidesmosomes and basement membrane were only observed in epithelium developed on 3T3- but not on conjunctival fibroblast-condensed collagen lattices. In contrast, goblet cell differentiation was only observed in epithelia developed on normal HCF-supported collagen matrix. Epithelial cells cultured on acellular collagen gels did not develop into multicell-layer epithelium, and no differentiated characteristics were observed. CONCLUSIONS: These results indicate that the type of fibroblasts dispersed in the collagen matrix plays an important role in the development and differentiation of conjunctival epithelial cells. Normal HCF-dispersed collagen matrix was less growth stimulating to epithelial cells and allowed them to undergo goblet cell differentiation. In contrast, 3T3-dispersed collagen matrix was more growth stimulating, resulting in thicker epithelium with a higher degree of stratification.

3T3 Cells↗

Experimental IgA nephropathy. Enhanced deposition of glomerular IgA immune complex in proteinuric states.

BACKGROUND: IgA nephropathy is induced by the IgA-immune complex (IC). IgA nephropathy associated with heavy proteinuria is considered a more progressive form of the disease. To elucidate the mechanism by which the latter condition occurs, we investigated the effect of proteinuria on the glomerular deposition of IgA-IC. EXPERIMENTAL DESIGN: BALB/c female mice that had been made proteinuric by adriamycin or bovine serum albumin (BSA) were injected with TEPC-15 hybridoma-derived IgA anti-phosphorylcholine (PC) and individual specific antigens. The 6-hour clearance kinetics of IgA were measured, and the accumulation of IgA deposits and the third complement component (C3) in the glomerulus were analyzed. RESULTS: The clearance kinetics of 125I-IgA injected together with a specific antigen, PC-conjugated BSA (BSA-PC), showed only a minimal distinction between the experimental (proteinuric) and the control (nonproteinuric) groups of mice. However, analysis of renal tissue by immunofluorescence and light microscopic autoradiography revealed markedly enhanced mesangial IgA-IC deposition in the proteinuric mice receiving IgA and one of three specific antigens, BSA-PC, PC-conjugated cytochrome-c, and a pneumococcal C-polysaccharide. Immunofluorescence also showed augmented mesangial C3 deposition in proteinuric mice that received IgA/PC-conjugated cytochrome-c or IgA/pneumococcal C-polysaccharide. In addition, adriamycin or BSA per se did not influence glomerular IgA-IC localization. CONCLUSIONS: Glomerular localization of nephritogenic IgA-IC was comparably enhanced in mice with proteinuria induced by various methods. Thus, a vicious cycle for the progression of IgA nephropathy might ensue in proteinuric states.

Animals↗

Lack of change in MnSOD during ischemia/reperfusion of isolated rat heart.

Decreased endogenous superoxide dismutase (SOD) activity has been implicated in free radical-mediated reperfusion injury of the ischemic myocardium. Antioxidant enzymes have been added to the modalities of reperfusion therapy of acute myocardial infarction based on this observation. We measured the content of MnSOD specific protein, activity of Mn and Cu, ZnSODs, and MnSOD mRNA in the working isolated rat heart subjected to various durations of ischemia and reperfusion. Recovery of mechanical function was monitored and lactate and lactic dehydrogenase released in the coronary effluent before and after ischemia were measured. In this model with reversible or irreversible myocardial injury, we noted no change in the myocardial MnSOD specific protein content and, contrary to some previous observations, no change in the activity levels of Mn or Cu,ZnSODs. Our results suggest that free radical-mediated damage in the heart during ischemia and reperfusion is probably not due to impaired activity or degradation of native SODs.

Analysis of Variance↗

Immunolocalization of manganese superoxide dismutase in normal and transgenic mice expressing the human enzyme.

The localization of manganese superoxide dismutase (MnSOD) was determined using immunohistochemistry of various tissues of normal and transgenic mice which express the human enzyme, with emphasis on studies of mouse kidney and lung. Mouse kidney and lung were studied using both frozen section analysis and paraffin sections following fixation in a variety of fixatives. Formalin fixation resulted in a loss of antigenicity, while fixation in zinc formalin or B5 fixative gave results similar to those from frozen sections. Immunoperoxidase studies using antibodies to MnSOD showed greater staining in transgenic kidney or lung than in identical tissues in normal mice when appropriate fixation was used. In contrast, equal immunostaining was obtained in kidney or lung from normal and transgenic mice when antibodies to catalase or copper zinc superoxide dismutase were utilized. Immunogold ultrastructural analysis of MnSOD localization for lung and kidney was also performed. As compared to normal mice, transgenic mice exhibited greater staining of the mitochondria of kidney interstitial fibroblasts and glomerular, endothelial, and smooth muscle cells. In the lungs of transgenic animals, all cells showed increased staining; smooth muscle cells demonstrated the most marked increase in immunolabelling. The results indicate that these transgenic mice overexpress MnSOD in their mitochondria, and that this occurs selectively in at least some mesenchymal tissues.

Animals↗

The int genes of bacteriophages P22 and lambda are regulated by different mechanisms.

Bacteriophage P22 and lambda are related bacteriophages with similar gene organizations. In lambda the cll-dependent Pl promoter is responsible for lambda int gene expression. The only apparent counterpart to pl in P22 is oriented in the opposite direction, and cannot transcribe the P22 int gene. We show that this promoter, called P(al), is active both in vivo and in vitro, and is dependent upon the P22 cll-like gene, called c1. We have also determined the DNA sequence of a 3.3 kb segment that closes the gap between previously reported sequences to give a continuous sequence between the P22 pL promoter and the int gene. The newly determined sequence is densely packed with genes from the pL direction, and the proteins predicted by the sequence show excellent correlation with the proteins mapped by Youderian and Susskind in 1980. However, the sequence contains no apparent genes in the opposite (p(al)) direction, and no additional binding motifs for the P22 c1 protein. We conclude that int gene expression in P22 is regulated by a different mechanism than in lambda.

Amino Acid Sequence↗

Distribution of manganese superoxide dismutase mRNA in normal and hyperoxic rat lung.

Aerobic metabolism requires a continuous oxygen supply, which in turn can form partially reduced species (free radicals) that damage cellular components. To prevent this, organisms have elaborate free radical-scavenging defenses that include the superoxide dismutases. The lungs are unique in their role as an oxygen-gathering system, making these defenses critical to lung integrity. Manganese superoxide dismutase (Mn-SOD) levels increase in rats exposed to sublethal doses of hyperoxia and correlate with the development of tolerance to higher levels of hyperoxia. Although pulmonary Mn-SOD protein and mRNA levels both change with hyperoxia, the timing and levels differ dramatically. Lung heterogeneity makes extrapolation of data from whole tissue homogenates or cultures difficult. In this study, in situ hybridization of Mn-SOD in the lungs of adult rats exposed to air or to 85% O2 for 3 days was performed. In animals exposed to either air or 85% O2, Mn-SOD transcripts were present in arterioles, the septal tips of alveolar ducts, alveolar type II cells, and mesothelial cells. Hyperoxic lung had an intense, continuous labeling of the pleura that was distinctly greater than the intermittent labeling of the pleura found in control animals. The high level of expression of Mn-SOD mRNA in alveolar duct septal tips in both control and O2-exposed animals may be secondary to increased aerobic activity in these regions, which contain collagen and elastin and are important stress-bearing elements in the lung. Alveolar type II cells are metabolically active secretory cells and thus may experience increased endogenously generated oxidative stress. Pleural effusions are common after hyperoxic exposures, suggesting damage to the mesothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗