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Biomedical subjects

C P Yang

Publications and source records attributed to C P Yang.

At least 37 records · Page 2Linked to original sources
PubMed1999

Successfully treated central nervous system Burkitt's lymphoma with minimal extraneural disease in a child.

Burkitt's lymphoma, the most common childhood non-Hodgkin's lymphoma, usually presents with abdominal tumors. Central nervous system (CNS) involvement in Burkitt's lymphoma is mostly secondary to advanced systemic disease, rarely with brain parenchymal lesions, and was previously recalcitrant to treatment. We report an unusual case of CNS Burkitt's lymphoma with minimal extraneural disease. This 10-year-old immunocompetent boy presented with increased intracranial pressure and seizures and was found to have multifocal intracerebral lesions on brain imaging studies. Cerebrospinal fluid studies confirmed the presence of Burkitt's lymphoma cells. Abdominal computed tomography showed bilateral nephromegaly with left intrarenal lesions that disappeared after three doses of intravenous dexamethasone. The patient was treated for 6.5 months according to the LMB 89 group C protocol of the French Pediatric Oncology Society. The response was brisk and complete. The patient has been disease free for more than 4 years, and is believed to be cured.

Brain Neoplasms↗
PubMed1999

Acute monoblastic leukemia in a child following chemotherapy for neuroblastoma.

The long-term effects of childhood cancer and its therapy are serious problems that deserve attention. One of the most important late effects is the development of secondary malignancy. We encountered a girl with neuroblastoma who developed acute monoblastic leukemia as a secondary malignancy, 32 months after starting treatment for the primary tumor at the age of 4 years and 10 months. For the primary tumor, she had received cyclophosphamide, ifosphamide, etoposide, epirubicin, cisplatin, and vincristine during a period of 20 months; no radiotherapy was given. Cytogenetic analysis of the leukemic cells showed no specific changes, but a rearrangement of the mixed lineage leukemia gene (chromosome 11q23 translocation) was subsequently found by reverse transcription polymerase chain reaction. The survival time after onset of the secondary malignancy was brief. The leukemogenic hazards of cancer treatment should be weighed against their therapeutic benefits.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Upregulation of caveolin-1 and caveolae organelles in Taxol-resistant A549 cells.

Caveolin is a principal component of caveolae membranes. It has been demonstrated that the interaction of the caveolin scaffolding domain with signaling molecules can functionally inhibit the activity of these molecules. Taxol is an antitumor agent that suppresses microtubule dynamics and binds to microtubules thereby stabilizing them against depolymerization. The drug also has been implicated in the induction of apoptosis through activation of components in signal transduction cascades. Here we have investigated the role of caveolin in the development of drug resistance by examining the expression of caveolins in low- and high-level drug-resistant cell lines. Caveolin-1, but not caveolin-2, was upregulated in highly multidrug resistant SKVLBI cells that express high levels of P-glycoprotein, and in low-level Taxol-resistant A549 cell lines that express low amounts of P-glycoprotein. Two drug-resistant A549 cell lines (one 9-fold resistant to Taxol and the other 1.5-fold resistant to epothilone B), both of which express no P-glycoprotein, demonstrate a significant increase in the expression of caveolin-1. These results indicate that in low-level epothilone B- or Taxol-resistant A549 cells, increased caveolin-1 expression occurs independently of P-glycoprotein expression. Electron microscopic studies clearly demonstrate the upregulation of caveolae organelles in Taxol-resistant A549 cells. Upregulation of caveolin-1 expression in drug-sensitive A549 cells was observed acutely beginning 48 h after incubation with 10 nM Taxol. Thus, caveolin-1 may play a role in the development of Taxol resistance in A549 cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Contrasting outcomes of donor-specific blood transfusion: effectiveness against cell-mediated but not antibody-mediated rejection.

BACKGROUND: Giving recipients a prior donor-specific blood transfusion (DST) is effective in prolonging organ allograft survival in some inbred strains but not in others. The present investigation analyzed two such contrasting strains of rats in an attempt to define the basis for this variation. METHODS AND RESULTS: The survival of fully mismatched Dark Agouti (RT1a) cardiac allografts was significantly prolonged (from 7 to 44 days, median survival times) in PVG (RT1c) rats given a prior (-14 day) DST, whereas it shortened survival in the high-responder PVG-RT1u strain. Injecting PVG recipients with blood from strains bearing defined differences indicated that each disparity contributed to the increased survival time in an incremental way: blood and heart matched at the MHC class I (A) and/or class II (B/D) loci had a major influence on survival; class I-like (C) and non-MHC antigens made only minor contributions. MHC disparities had contrasting effects in RT1u rats. Blood transfusions from Dark Agouti or PVG-R8 (AaB/DuCu) rats induced accelerated rejection and anti-Aa alloantibody formation; transfusing PVG-R23 (AuB/DaCa) blood, a class II and class I-like difference, induced indefinite R23 heart allograft survival. Although produced in high titer, anti-class II antibody was not able to induce rejection in RT1u rats. Specific anti-Aa alloantibody was able, after passive transfer, to destroy class I-disparate allografts in both RT1u nude and PVG nude recipients. However, under normal circumstances, acute rejection in the PVG strain occurred in the absence of anti-Aa antibodies, presumably by a cell-mediated mechanism. CONCLUSION: Anti-class I alloantibody, when produced, seemed to override the unresponsiveness induced by DST. The results indicated that DST was effective only when rejection was induced by a cell-mediated response. The two contrasting response patterns in animals may reflect the experience of transplant patients who either benefit from DST or become sensitized instead.

Animals↗
PubMed1998

Identification of the domains of photoincorporation of the 3'- and 7-benzophenone analogues of taxol in the carboxyl-terminal half of murine mdr1b P-glycoprotein.

P-glycoprotein is an ATP-dependent drug-efflux pump that can transport a diverse range of structurally and functionally unrelated hydrophobic compounds across the plasma membrane. The transporter is composed of two homologous halves, each containing a nucleotide binding fold and six putative transmembrane spanning segments. The contact domains between the murine mdr1b P-glycoprotein and two photoreactive Taxol analogues have been mapped by a combination of CNBr digestion and immunoprecipitation studies. We had demonstrated previously that the 3'-p-benzoyldihydrocinnamoyl (BzDC) analogue of Taxol specifically photolabeled mdr1b P-glycoprotein and now show that the corresponding C-7 analogue likewise specifically photoincorporates into the transporter. CNBr digestion of both photolabeled P-glycoproteins gave rise to an approximate 10 kDa tritium-labeled peptide, each of which was a distinct polypeptide. The CNBr fragment generated from the 3'-BzDC-Taxol-photolabeled P-glycoprotein was immunoprecipitated by a polyclonal antibody (Ab7) raised against amino acid residues 1008-1019 of the mdr1b isoform. In contrast, the CNBr fragment generated from the 7-BzDC-Taxol-photolabeled P-glycoprotein was immunoprecipitated by a polyclonal antibody (Ab4) raised against amino acid residues 740-750. The specificity of these reactions was demonstrated by showing that the presence of the appropriate synthetic peptide blocked the immunoprecipitation. Moreover when the antibodies were reversed, no immunoprecipitation occurred. Based on the deduced amino acid sequence of mdr1b P-glycoprotein, and its hydropathy plot analysis, our data indicated that the 3'-BzDC group photoincorporates into amino acid residues 985-1088, a region of the transporter that includes half of TM 12 and terminates just after the Walker A motif in the second nucleotide binding fold. The 7-BzDC group photoincorporates into amino acid residues 683-760, a region of the transporter that includes all of TM 7 and half of TM 8 plus the intervening extracellular loop.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Neoangiogenesis and sinusoidal "capillarization" in dysplastic nodules of the liver.

The blood supply of hepatocellular carcinoma (HCC) is primarily arterial. Recent studies reported differences of vascular, especially arterial, supply among low- and high-grade dysplastic nodules and HCC. We assessed arterialization using monoclonal antibody specific for smooth muscle actin as well as simultaneous changes in sinusoidal capillarization in cirrhotic nodules, dysplastic nodules, and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low-grade dysplastic nodules, 27 high-grade dysplastic nodules, and 20 HCCs for alpha smooth muscle actin (to identify unpaired arteries (i.e., arteries not accompanied by bile ducts) and CD34 (indicating sinusoidal capillarization). Distribution and number of unpaired arteries and distribution of sinusoidal capillarization were graded semiquantitatively. Unpaired arteries were rare in cirrhotic nodules, significantly more common in dysplastic nodules of both types (p < 0.00001), and most common in HCC. Sinusoidal capillarization was least common in cirrhotic nodules, significantly more common in dysplastic nodules (p < 0.0035), and most common in HCC. No topographic relationship between unpaired arteries and sinusoidal capillarization was identified. These findings showed that (1) distributions of sinusoidal capillarization and unpaired arteries in dysplastic nodules are intermediate between those in cirrhotic nodules and HCC, supporting dysplastic nodules as premalignant lesions; (2) unpaired arteries are histologically useful for distinguishing dysplastic nodules from large cirrhotic nodules; and (3) areas of sinusoidal capillarization within dysplastic nodules are unrelated to location of arterialization.

Actins↗
PubMed1998

The first case of the p phenotype in a Gurkha Nepalese.

A serum sample from a Gurkha Nepalese soldier, residing in Hong Kong, was found to cause hemolysis of reagent ABO red cells (RBCs) in the reverse blood grouping test. Subsequent follow-up studies revealed that he was of the p phenotype, with potent anti-PP1Pk that was strongly hemolytic both at room temperature and 37 degrees C. The anti-PP1Pk was composed of IgG and IgM, and its various components were separable.

Journal Article↗
PubMed1997

Taxol induces tyrosine phosphorylation of Shc and its association with Grb2 in murine RAW 264.7 cells.

Taxol, a natural product with significant anti-tumor activity, stabilizes microtubules and arrests cells in the G2/M phase of the cell cycle. It has been reported that taxol has additional effects in cells, including an increase in tyrosine phosphorylation of proteins and activation of MAP kinase. We investigated a possible effect of taxol on tyrosine phosphorylation of Shc and on formation of the Shc/Grb-2 complex in the murine macrophage-like cell line RAW 264.7. Shc, an SH2 domain containing adaptor protein, was immunoprecipitated from lysates of taxol-treated cells with anti-phosphotyrosine antibody and its identity determined by Western blotting with anti-Shc antibody. Non-denatured Shc containing protein complexes were immunoprecipitated with anti-Shc antibody, and analysis with an anti-Grb2 antibody revealed the presence of the 24-kDa Grb2 protein. Taxol also activated Raf-1 kinase and ERK1/ERK2 MAP kinases in these cells. These results demonstrate that taxol affects tyrosine phosphorylation of Shc and this may result in the activation of the Raf-1/MAPK cascade.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Hepatitis C and G virus infections in polytransfused children.

UNLABELLED: The prevalence of hepatitis C virus (HCV) and a newly identified hepatitis G virus (HGV) and their clinical significance were studied in 42 polytransfused Taiwanese children. Serological assays for antibodies against HCV (anti-HCV) and polymerase chain reaction for serum HCV ribonucleic acid (RNA) and HGV RNA were performed. The prevalence of anti-HCV and HGV RNA was 17% and 14%, respectively in 42 polytransfused children. Anti-HCV seropositives had a significantly higher mean age, peak serum transaminase level, and longer transfusion duration than seronegatives, while children with HGV infection usually had no or only mild hepatitis activities. The prevalence of anti-HCV dropped sharply after implementation of anti-HCV screening, however the prevalence of HGV viraemia remained unchanged. CONCLUSIONS: HGV infection is not uncommon in polytransfused Taiwanese children and the virus does not cause significant hepatitis compared to HCV infection. Current blood donor screening for anti-HCV can effectively protect polytransfused children from HCV infection but the impact of additional screening for HGV markers awaits further studies.

Adolescent↗
PubMed1997

Hepatic stellate cell activation in dysplastic nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis.

We have previously suggested that dysplastic nodules (also referred to as "adenomatous hyperplasia" or "macroregenerative nodules"), likely precursors of hepatocellular carcinoma (HCC), develop as an infiltrating clonal expansion, in advance of or parallel to cirrhosis. As part of this hypothesis, to explain aspects of their gross and microscopic appearance, we suggested that dysplastic nodules are resistant to the scarring process affecting the rest of the liver. We sought to test this hypothesis by examining the distribution of activated hepatic stellate cells (HSCs), the hallmark of hepatic scarring, in cirrhotic nodules, dysplastic nodules and HCC. We immunohistochemically stained 56 cirrhotic nodules, 20 low grade dysplastic nodules, 27 high grade dysplastic nodules, and 20 HCCs with monoclonal antibodies against alpha-smooth muscle actin to identify activated HSCs. Distribution and number of HSCs were graded semiquantitatively (0 to 4+). In our results, HSCs were significantly less widespread in dysplastic nodules than in cirrhotic nodules or in HCCs (both: p < 0.00001). HSCs were also more prominent in the periphery of dysplastic nodules than in the center, though still fewer in number than in cirrhotic nodules. In conclusion, the low number of activated HSCs in dysplastic nodules, compared to both cirrhotic nodules and HCC, supports our hypothesis concerning dysplastic nodule development: that they arise as clonal expansions of neoplastic hepatocytes in advance of, or parallel to, the development of cirrhosis.

Actins↗
PubMed1996

Prevention of chronic rejection by donor-specific blood transfusion in a new model of chronic cardiac allograft rejection.

Chronic graft rejection is now a major barrier to the long-term survival of cardiac transplants. A major hallmark of chronic rejection is intimal thickening of arteries in the graft leading to vascular occlusion. Current animal models of chronic rejection generally utilize immunosuppression to prevent acute rejection of grafts disparate at major histocompatibility antigens or graft disparities involving minor histocompatibility antigens alone. In the present communication we describe a new model of chronic rejection involving grafting of PVG-R23 hearts into PVG-RT1(u) recipients. The R23 hearts, which differ from the RT1(u) recipients at class II MHC, are rejected with a chronic time course and demonstrate extensive severe vascular myointimal proliferation within the coronary arteries. Furthermore we demonstrate for the first time that donor-specific blood transfusion can prevent chronic rejection and the intimal thickening of the coronary arteries.

Animals↗
PubMed1996

Autoimmune MRL mice express high-affinity IgG2b monoclonal autoantibodies to heparin.

Heparin and heparan sulfate are related glycosaminoglycans which demonstrate high-affinity interactions with a number of proteins, including antithrombin III. The immunogenicity of heparin has been reported previously employing heparin-protein conjugates as immunogens and as antigens in solid-phase assays. Previous studies also demonstrate that anti-heparin antibodies play a role in autoimmune diseases including systemic lupus and anti-phospholipid syndrome and in patients who receive heparin for therapeutic purposes. In the current study, we investigated the expression of monoclonal anti-heparin antibodies in nonimmunized, autoimmune MRL/lpr/lpr++ mice employing a liquid-phase radioimmunoassay. The Kd of monoclonal IgG2b autoantibodies for heparin was approximately 10(-8)M. Anti-heparin antibodies were precipitating, and were not polyreactive. The IgG monoclonal antibodies described in this study represent an immunological instance of a specific, high-affinity heparin-protein interaction.

Animals↗
PubMed1996

Localization of sequences that influence basal and cell type-specific activity of the murine mdr2 promoter.

The mdr2 gene is highly expressed in liver and is involved in the translocation of phospholipid. To study the regulation of mdr2 expression, the promoter of the mdr2 gene has been isolated from a murine vinblastine-resistant cell line, J7.V2-1, and characterized. The 5' flanking region of this gene is GC-rich, has multiple transcription initiation sites as mapped by primer extension, and does not contain either TATA or CCAAT boxes. To test promoter activity, a 1.9-kb (-1867 to +37) DNA fragment was cloned in front of the luciferase reporter gene and transient transfection assays were done in a variety of cell lines. The promoter-luciferase construct displayed a 20- to 120-fold increase in activity compared to the promoterless vector. 5' and 3' deletion analysis using transient transfections revealed two major regulatory regions in the promoter, one located upstream and one situated downstream of the transcription start sites. The upstream region may be involved in basal expression and the downstream sequence may be involved in cell type-specific expression of the mdr2 gene. Gel mobility shift and DNA footprinting assays have identified a 29-bp sequence (-78 to -50) to which nuclear protein binds. Methylation interference analysis using this fragment has further determined that CTGGCAGCTCGCCC, within the 29-mer, contains the core sequence with which nuclear protein directly interacts. Mutation of the core sequence reduced basal promoter activity, indicating that it is involved in the basal expression of the mdr2 gene. Mutagenesis studies also suggested that the upstream and downstream sequences act independently in regulation of cell type-specific mdr2 expression.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1996

Early-onset sepsis in children with acute lymphoblastic leukemia.

The presence of early-onset sepsis significantly affects the prognosis of childhood acute lymphoblastic leukemia (ALL). We retrospectively analyzed all the septic episodes that occurred within 30 days of diagnosis of ALL from January 1978 to June 1994. Within the study period, 51 early septic episodes occurred in 45 patients. This accounted for 36.2% of the total number of septic episodes (141) that occurred during this period. The rate of early-onset sepsis in childhood ALL was 11.3% (45/397). The patients ages ranged from 11 months to 14.7 years. Fortyeight episodes of sepsis were caused by single organisms and three were polymicrobic. Pseudomanas aeruginosa was the most common isolate, followed closely by Staphylococcus aureus, Escherichia coli, Streptococcus spp and Salmonella spp. The case fatality rate of early-onset sepsis was 35.6% (16/45). The average time between diagnosis and death was 5.2 days (median, 1 d). Sepsis caused by P. aeruginosa had the highest mortality, with a case fatality rate of 72.7% (8/11), followed by polymicrobial infections (66.7%, 2/3) and candidemia (66.7%, 2/3). In the adolescent age group, initial white blood cell count < 2.0 x 10(9)/L, and depressed immunoglobulin level (especially IgA) were risk factors for a fatal outcome. During the study period, which covered 16.5 years, the incidence of Gram-positive cocci, especially Streptococcus spp, increased significantly and the overall outcome associated with early-onset sepsis improved.

Adolescent↗
PubMed1995

CD45RC+ CD4 T cell subsets are maintained in an unresponsive state by the persistence of transfusion-derived alloantigen.

The ability of preoperative blood transfusion to extend the survival of organ allografts is well known but poorly understood. To study this phenomenon, adult PVG (RT1c) rats were rendered tolerant of DA (RT1a) cardiac allografts by prior donor-specific blood transfusion (DST). We investigated the cellular basis of the transfusion effect by adoptively transferring CD4 T cell subsets, obtained from thoracic duct lymph of tolerant rats, into cardiac allografted athymic PVG nude recipients. Surprisingly, CD4 T cells from DST rats evoked acute rejection on adoptive transfer. Evidence indicated that CD8 T cells played no role in DST-induced tolerance. Analysis of CD4 T cell subsets, defined in the rat by mAb OX22 (anti-CD45RC), revealed an unusual pattern of responsiveness. CD45RC+ CD4 T cells (normally capable of inducing prompt rejection), when obtained from rats given a specific blood transfusion, were depleted of alloreactive cells and deficient at inducing rejection. In contrast, the CD45RC- subset (normally slow at evoking graft destruction) was highly active and ten-fold-enriched in its ability to induce rejection. Destruction of cardiac allografts by this latter subset was, however, completely inhibited by giving nude recipients a specific (but not a third-party) blood transfusion two weeks before heart grafting and cell transfer. Apparently, tolerance was maintained by residual elements of the prior blood transfusion that prevented the specific CD45RC- subset from regaining an alloaggressive capacity.

Animals↗
PubMed1995

Cytotoxicity to endothelial cells by sera from aged MRL/lpr/lpr mice is associated with autoimmunity to cell surface heparan sulfate.

Vasculitis is an common clinical feature of systemic lupus erythematosus (SLE) in humans and in animal models of this disease. Humoral autoimmunity against endothelial cells has been previously demonstrated in SLE and other autoimmune disorders, but the precise cell surface antigenic targets involved in the initiation and progression of vascular injury are still essentially unknown. In the current studies, we demonstrate the presence of autoantibodies in the sera of MRL/lpr/lpr mice which bind endothelial cell surface antigens by ELISA and also cause complement-dependent cytotoxicity of these cells. These MRL/lpr/lpr sera induced complement-dependent cleavage and release of 35SO4-labeled material containing primarily cell surface heparan sulfate proteoglycans from these cells, and react with heparin (a glycosaminoglycan related to heparan sulfate) by ELISA and liquid-phase competitive inhibition ELISA. These data indicate that antiendothelial cell autoantibodies present in autoimmune MRL/lpr/lpr mice are directed at least in part against cell surface heparan sulfate proteoglycans. Autoantibodies to cell surface heparan sulfate proteoglycan may play a role in vascular endothelial cell injury in these animals through complement-dependent, autoimmune mechanisms.

Animals↗
PubMed1995

Determination of lead, cadmium, mercury, and copper concentrations in duck eggs in Taiwan.

Samples of duck eggs were collected from 65 farms distributed in 6 counties in Taiwan to analyze the contents of Pb, Cd, Hg, and Cu in albumen and yolk. Lead, Cd, and Cu determinations were performed by microwave digestion together with atomic absorption spectrophotometry, whereas Hg was analyzed by sulfuric acid-nitric acid digestion and cold vapor atomic absorption spectrophotometry. Expressed on a wet weight basis, the average concentrations (ranges) of the four metals were as follows: Pb, 13.6 ng/g (.8 to 27.5) in albumen and 84.7 ng/g (44.8 to 224.7) in yolk; Cd, 1.8 ng/g (< .5 to 4.4) in albumen and 3.8 ng/g (< 1.0 to 5.7) in yolk; Hg, 17.8 ng/g (2.5 to 47.5) in albumen and 9.7 ng/g (1.2 to 20) in yolk; Cu, .83 micrograms/g (.56 to 1.08) in albumen and 1.36 micrograms/g (.95 to 1.95) in yolk. Comparison of the calculated daily intakes of Pb, Cd, and Hg from eggs with the World Health Organization-Food Agriculture Organization provisional tolerated daily intakes suggest that duck eggs are safe with respect to the contents of the three metals. Eggs are poor sources of Cu, supplying less than 2% of the Recommended Dietary Allowance.

Animals↗