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Biomedical subjects

L Y Yang

Publications and source records attributed to L Y Yang.

At least 55 records · Page 3Linked to original sources
PubMed1994

Cellular accumulation and DNA damage induced by liposomal cis-bis-neodecanoato-trans-R,R-1,2-diaminocyclohexaneplatinum+ ++(II) in LoVo and LoVo/PDD cells.

Liposomal cis-bis-neodecanato-trans-R,R-1,2-diaminocyclohexaneplatinum (11) (L-NDDP) is a liposome-entrapped platinum complex that has shown partial lack of cross-resistance with cisplatin in human colon carcinoma LoVo cells. We studied the drug accumulation and DNA damage induced by L-NDDP and cisplatin in LoVo and LoVo/PDD cells. Our results indicate that the accumulation of L-NDDP in LoVo cells is several-fold higher than that of cisplatin; that the accumulation of L-NDDP is similar in both cell lines, whereas that of cisplatin is reduced by 2- to 3-fold in LoVo/PDD cells; and that the transmembrane transport of cisplatin is highly dependent on temperature while that of L-NDDP is not. We also found that the cytotoxicity of both agents correlates with the extent of DNA-protein cross-link formation, and that DNA interstrand cross-linking does not appear to play a role in the cytotoxicity of L-NDDP, whereas it correlates with cisplatin cytotoxicity.

Antineoplastic Agents↗
PubMed1994

[In situ hybridization and immunohistochemical detection of bone morphogenetic protein genes in ameloblastomas].

Bone morphogenetic protein (BMP) is related to the formation of bone and dentin. Immunohistochemical study showed that ameloblasts, odontoblasts and dental papilla cells contained much BMP. It is indicated BMP might be associated with the epothelial-mesenchymal interaction of tooth germs. In this study, the expression and distribution of BMP in 40 patients with ameloblastomas were observed by using in situ hybridization and immunohistochemistry. The results showed that all three BMP genes were overexpressed in the epithelial component of ameloblastomas, however, no positive reaction was found in immunohistochemistry. It is indicated that overexpression of BMP genes might be related to the development of ameloblastomas.

Ameloblastoma↗
PubMed1994

Lupus nephritis in children--a review of 167 patients.

BACKGROUND: Relatively few studies have been made of children with lupus nephritis. The prognosis of children with lupus nephritis is ominous for those with diffuse proliferative glomerulonephritis and active interstitial inflammation. Up to now few studies have been made on this subject. OBJECTIVES: To evaluate the clinical course, histopathology, and prognosis of lupus nephritis in children, to identify the risk factors for renal failure and mortality, and to share our experience in treating lupus nephritis in children. METHODS: Retrospectively, 167 children under 18 years of age with lupus nephritis at Veterans General Hospital-Taipei, Taiwan from 1979 to 1991 were studied. All patients received renal biopsy and follow-up biopsies were performed in 36 children. The clinical and serologic parameters at the time of renal biopsy were recorded. RESULTS: There were 55 (33%) patients with class II, 30 (18%) with class III, 69 (41.3%) with class IV, and 13 (7.8%) with class V nephritis based on initial biopsy. The mean follow-up time was 59 months. Follow-up biopsies were histologically stationary in 29 patients, progressive in five, and regressive in two. The results revealed that those with persistent hypertension, anemia, increased serum creatinine concentration, and decreased creatinine clearance rate at initial biopsy were more prone to develop renal failure. Low titer of CH50 hemolytic assay appeared to be a poor prognostic indicator. The overall renal and patient 5-year survival rates were 93.1% (135/145) and 91.08% (143/157), respectively. They were 87.7% (50/57) and 82% (55/67), respectively, of patients with class IV proliferative glomerulonephritis. CONCLUSIONS: The prognosis of children with class IV nephritis in this study was better than that reported previously. All children surviving without renal failure were maintaining their normal lives with little organ dysfunction. The improved results may be due to earlier renal biopsy for precise histopathologic definition, better supportive care, and selective use of aggressive therapy, including methylprednisolone pulse therapy, intravenous cyclophosphamide, intravenous prostaglandin E1 therapy, high-dose intravenous gammaglobulin therapy, and cyclosporin A for those with high risk factors.

Adolescent↗
PubMed1993

In vitro cytotoxicity, cellular pharmacology, and DNA lesions induced by annamycin, an anthracycline derivative with high affinity for lipid membranes.

Annamycin (AN) is an anthracycline antibiotic with high affinity for lipid membranes which is being developed for clinical studies formulated in liposomes. We studied the in vitro cytotoxicity, cellular pharmacology, and DNA damage induced by AN in P388 cells sensitive and resistant to doxorubicin (DOX). AN was as cytotoxic as DOX against P388-sensitive cells and about 50 times more cytotoxic than DOX against P388-resistant cells (resistance index 5 for AN versus 250 for DOX). Cellular uptake of AN by sensitive cells was 2-3-fold higher than that of DOX. In resistant cells, cellular uptake of AN and DOX was approximately 65% and 30%, respectively, of the cellular uptake in sensitive cells. As a result, cellular uptake of AN by resistant cells was higher than uptake of DOX by sensitive cells. DOX was fully retained in sensitive cells while it was effluxed rapidly from resistant cells. In contrast, efflux of AN was similar in sensitive and resistant cells, thus suggesting that it is not mediated by P-glycoprotein. AN was more effective than DOX in inducing single DNA breaks, double DNA breaks, and DNA-protein cross-links, both in sensitive and resistant cells, although DNA damage was lower in resistant cells than in sensitive cells. DNA lesions induced by AN in resistant cells were similar to or greater than those induced by DOX in sensitive cells. These studies indicate that the lack of cross-resistance between DOX and AN appears to be related, at least in part, to the relatively higher cellular uptake of AN compared with DOX and is associated with the ability of AN to induce significant DNA damage in resistant cells.

Animals↗
PubMed1993

Distinct P-glycoprotein expression in two subclones simultaneously selected from a human colon carcinoma cell line by cis-diamminedichloroplatinum (II).

Two drug-resistant sublines, CP2.0 and RT, were simultaneously selected by cis-diamminedichloroplatinum (CDDP) from the human colon carcinoma cell line LoVo by the conventional method of continuous drug exposure. The 2 sublines differed in morphology, growth kinetics and pattern of gene expression. Genetic signature analysis indicated that the lines were independent subclones but that both arose from LoVo. These sublines were maintained in a growth medium containing 2.0 micrograms/ml CDDP. However, CP2.0 cells were 3 times more resistant to CDDP than were RT cells. Although both were cross-resistant to mustargen and 5-fluorouracil, only CP2.0 was resistant to Adriamycin and vincristine. Western-blot analysis, immunocytochemical staining and in vitro phosphorylation experiments indicated that the level of P-glycoprotein was significantly elevated in CP2.0 but not in RT. Despite the differences between these sublines, they possess similar CDDP-resistance mechanisms, including decreased intracellular CDDP accumulation, elevated levels of glutathione and metallothionein-like proteins, increased glutathione transferase-pi mRNA, and enhanced susceptibility to CDDP cytotoxicity after treatment with DL-buthionine-[S,R]-sulfoximine. Nevertheless, our results suggest that, in certain tumor types, P-glycoprotein-mediated multi-drug resistance and CDDP-resistance phenotypes can coexist in cells with primary resistance to CDDP.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

New initiatives with fludarabine monophosphate in hematologic malignancies.

Fludarabine monophosphate (fludarabine) was initially discovered to have significant activity in indolent lymphoma and chronic lymphocytic leukemia (CLL). The major clinical experience with fludarabine is in previously treated patients with CLL. In such patients the complete and partial response rate (CR + PR) is over 50%. These results were obtained with 5-day schedules of fludarabine 25 to 30 mg/m2/d. Subsequent schedules have explored once-a-week fludarabine and a 3-day schedule every 4 weeks. These strategies, in particular the once-a-week schedule, have obtained inferior results. The addition of prednisone has not been associated with an improvement in response rate or survival. The application of fludarabine to previously untreated patients demonstrated a CR + PR rate of 75% to 80%. The addition of prednisone did not improve the response rate or survival in this group of patients. A significant concern in patients with CLL treated with fludarabine is a decrease in the CD4 and CD8 counts. Despite median posttreatment counts of approximately 200 CD4 lymphocytes/microL, the incidence of infections in patients in remission off therapy is low. Major clinical activity has been demonstrated with fludarabine in Waldenstrom's macroglobulinemia, in which more than one third of refractory patients achieve a CR or PR. Responding patients with anemia or thrombocytopenia have a marked improvement in blood counts. The duration of response has been long (> 30 months) in most responders. The early activity of fludarabine as a single agent in phase I/II studies in indolent lymphoma subsequently has been confirmed by a number of investigators. Fifty percent to 60% of patients with follicular lymphomas respond to fludarabine as a single agent. A number of these responses are complete despite the patients having received extensive prior treatment. A number of combination programs are being developed in CLL and indolent lymphoma. The combination of fludarabine with doxorubicin and prednisone has been developed and is being studied in phase I/II clinical trials. In addition, combinations of fludarabine and cytarabine with or without cisplatin based on elegant preclinical pharmacokinetic rationales have been applied to CLL with impressive cytoreductive activity but significant myelosuppression. A new combination of fludarabine, mitoxantrone, and dexamethasone has been developed for use in lymphoma. Phase I studies demonstrated a high response rate, especially in follicular lymphomas, with a number of patients achieving complete remission. Subsequent phase II studies demonstrate a response rate of 89% in patients with indolent lymphoma.(ABSTRACT TRUNCATED AT 400 WORDS)

Antimetabolites, Antineoplastic↗
PubMed1993

Fludarabine: pharmacokinetics, mechanisms of action, and rationales for combination therapies.

Knowledge of the pharmacokinetics of a drug is essential to the optimal design of the dose and schedule of chemotherapy protocols. As an extension, an understanding of the mechanism of drug action is necessary to construct the optimal strategy for combination chemotherapy. Nucleoside antimetabolites such as fludarabine are pro-drugs that must enter cells and be phosphorylated to the nucleoside triphosphate before they can elicit biologic activity. Thus, knowledge of the pharmacokinetics of the triphosphate in target cells and an understanding of the mechanisms by which this active form of the drug act are indispensable to the rational design of treatment protocols. This article reviews the essential elements of the pharmacokinetics and mechanisms of action of fludarabine to provide a rationale for combinations of fludarabine with other chemotherapeutic agents and anti-cancer modalities.

Antineoplastic Agents↗
PubMed1992

Surface components of chylomicrons from rats fed glyceryl or alkyl esters of fatty acids: minor components.

The lipid class, fatty acid and molecular species composition of the minor polar surface components of rat lymph chylomicrons were determined during absorption of menhaden oil and corn oil or of the corresponding fatty acid ethyl esters. In addition to the previously reported minor polar lipids (sphingomyelin, phosphatidylserine, phosphatidylinositol, phosphatidic acid and lysophosphatidylcholine), we identified phosphatidylglycerol, dimethylphosphatidylethanolamine, ceramide and cholesteryl sulfate in the chylomicrons from both oil and ester feeding. The dietary fatty acids were found to be incorporated to a variable extent into the different phospholipid classes, the proportions of which remained the same during both types of feeding. No evidence was obtained for the presence of the minor glycerophospholipids characteristic of the lysosomal membranes (e.g., bis-phosphatidic, lysobisphosphatidic and semilysobis-phosphatidic acids), although special efforts were made to identify them. These results indicate that the chylomicrons arising from the monoacylglycerol and phosphatidic acid pathways of triacylglycerol biosynthesis become enveloped in closely similar monolayers of phospholipids. Hence, all triacylglycerols may be secreted from the villus cells via a common mechanism as suggested by the previously demonstrated convergence (at the 2-monoacylglycerol stage) of the monoacylglycerol and the phosphatidic acid pathways of mucosal triacylglycerol formation [Yang, Y.L., and Kuksis, A. (1991) J. Lipid Res. 32, 1173-1186].

Animals↗
PubMed1992

Reattachment of surface array proteins to Campylobacter fetus cells.

Campylobacter fetus strains may be of serotype A or B, a property associated with lipopolysaccharide (LPS) structure. Wild-type C. fetus strains contain surface array proteins (S-layer proteins) that may be extracted in water and that are critical for virulence. To explore the relationship of S-layer proteins to other surface components, we reattached S-layer proteins onto S- template cells generated by spontaneous mutation or by serial extractions of S+ cells with water. Reattachment occurred in the presence of divalent (Ba2+, Ca2+, Co2+, and Mg2+) but not monovalent (H+, NH4+, Na+, K+) or trivalent (Fe3+) cations. The 98-, 125-, 127-, and 149-kDa S-layer proteins isolated from strains containing type A LPS (type A S-layer protein) all reattached to S- template cells containing type A LPS (type A cells) but not to type B cells. The 98-kDa type B S-layer protein reattached to SAP- type B cells but not to type A cells. Recombinant 98-kDa type A S-layer protein and its truncated amino-terminal 65- and 50-kDa segments expressed in Escherichia coli retained the full and specific determinants for attachment. S-layer protein and purified homologous but not heterologous LPS in the presence of calcium produced insoluble complexes. By quantitative enzyme-linked immunosorbent assay, the S-layer protein copy number per C. fetus cell was determined to be approximately 10(5). In conclusion, C. fetus cells are encapsulated by a large number of S-layer protein molecules which may be specifically attached through the N-terminal half of the molecule to LPS in the presence of divalent cations.

Animals↗
PubMed1992

Class IV lupus nephritis associated with Graves' disease.

Graves' disease was initially diagnosed in an 11-year-old Chinese boy in March 1989. After regular propylthiouracil (PTU) and thyroxine, he achieved a euthyroid state. Heavy proteinuria with class IV lupus glomerulonephritis, anemia, arthralgia, low serum complement and anti-dsDNA (+) appeared 15 months later. Thyrotoxicosis also relapsed at this time. His condition fitted the diagnostic criteria of systemic lupus erythematosus. His antimicrosomal antibody titer was 1:1,600 (+) thyroid-stimulating hormone receptor antibody level was strongly positive, and the titer of antiinsulin antibody was high as well. These clinical, laboratory and histological findings indicate that class IV lupus nephritis may be associated with Graves' disease.

Carbimazole↗
PubMed1991

Similarities in surface lipids of chylomicrons from glyceryl and alkyl ester feeding: major components.

This study tests the hypothesis that the rat chylomicrons are assembled and released into lymph similarly regardless of the site (rough or smooth endoplasmic reticulum) or pathway (phosphatidic acid or monoacylglycerol) of triacylglycerol biosynthesis. For this purpose we determined the lipid class, fatty acid and molecular species composition of the choline, ethanolamine, inositol and serine phospholipids of lymph chylomicrons during absorption of menhaden, mustard-seed and corn oil (monoacylglycerol pathway) or the corresponding fatty acid methyl or ethyl esters (phosphatidic acid pathway). The dietary fatty acids were found to be incorporated to various extents into different phospholipid classes, the proportions of which were not affected by the nature of the dietary fat. The chylomicron phospholipids contained 80-82% choline, 8% ethanolamine and 2.5% inositol glycerophospholipids, and much smaller amounts of serine and other minor phospholipids. Administration of a meal of each dietary fat resulted in a retention of approximately 50% endogenous fatty acids in the major glycerophospholipids of the chylomicrons. A minimum of 50% of the molecular species of the choline and ethanolamine glycerophospholipids contained at least one exogenous fatty acid. No significant discrepancies were found in the fatty acid and molecular species composition of the glycerophospholipids between chylomicrons from the oil and corresponding ester feeding. It is concluded that the chylomicrons arising from the monoacylglycerol (oil feeding) and the phosphatidic acid (ester feeding) pathways of triacylglycerol biosynthesis become enveloped in surfactant monolayers containing qualitatively and quantitatively identical classes and molecular species of phospholipids.

Animals↗
PubMed1991

Induction of NAD(P)H:quinone reductase in human peripheral blood lymphocytes.

The induction of quinone reductase [QR; NAD(P)H:(quinone acceptor) oxidoreductase; EC 1.6.99.2] in cultured cells and animal tissues of rodents has provided useful information on mechanisms of protection against carcinogens. We have developed a simple and efficient microtiter plate assay for the direct measurement of QR basal activity and inducibility in human peripheral blood lymphocytes (unstimulated, mitogen-stimulated and Epstein-Barr virus-transformed) grown in suspension culture. In these cells, QR was induced by monofunctional (electrophilic) inducers (i.e. 1,2-dithiole-3-thione, dimethyl fumarate, methyl vinyl sulfone) but not by bifunctional inducers (i.e. 1,1'-azonaphthalene, beta-naphthoflavone, 2,3,7,8-tetrachlorodibenzo-p-dioxin). QR is a major enzyme of xenobiotic metabolism that carries out obligatory two-electron reductions and thereby protects cells against the toxicity of quinones. It is induced in many tissues coordinately with other enzymes that protect against electrophiles. Since lymphocytes can be sampled easily and repetitively in man, this system may provide a simple short-term marker for assessing the capacity of tissues to detoxify electrophiles, such as quinones, and for measuring the response to inducers.

Adult↗
PubMed1991

Endotracheal administration of epinephrine during cardiopulmonary resuscitation.

A hypoxia-induced canine cardiac model was used to study the effectiveness hemodynamic response, arterial blood gas and pulmonary pathologic changes after endotracheal (ET) epinephrine administration in comparison with those from intravenous (IV) administration. The results indicated that the survival rate was the same with the drug given by either route. The increase of hemodynamic indices was lower in the group after ET administration than that after IV administration. No significant influence was exerted on the drug effects whether the drug is diluted in normal saline or in distilled water and no serious detrimental effects occurred on the lung tissues following ET epinephrine administration.

Animals↗
PubMed1991

Apparent convergence (at 2-monoacylglycerol level) of phosphatidic acid and 2-monoacylglycerol pathways of synthesis of chylomicron triacylglycerols.

Dietary fats are converted into chylomicron triacylglycerols via the 2-monoacylglycerol and phosphatidic acid pathways of acylglycerol formation. In view of the known positional and fatty acid specificity of the acyltransferases, the triacylglycerol structures resulting from the two pathways would be expected to differ, but this has not been demonstrated. We have performed stereospecific analyses on the chylomicron triacylglycerols from rats fed menhaden oil and the corresponding fatty acid alkyl esters, which would be expected to be assimilated via the monoacylglycerol and the phosphatidic acid pathways, respectively. The results show a remarkable similarity between the two triacylglycerol types in the fatty acid composition of the sn-1 and sn-3 positions, along with marked differences in the composition of the sn-2 positions. The triacylglycerols from rats fed oil retained about 85% of the original fatty acids in the sn-2 position, including a high proportion of the long chain polyunsaturates (e.g., 5-7% 20:5 and 4-5% 22:6). The triacylglycerols from rats fed the alkyl ester contained large amounts of endogenous fatty acids in the sn-2 position (e.g., 18% 16:1, 14% 18:1, 14% 18:2, and 2.5% 20:4), which approximated the composition of the sn-2 position of the presumed phosphatidic acid intermediates. The sn-1 position contained a much higher proportion of polyunsatured fatty acids (e.g., 12-13% 20:5, 5-6% 22:6) than the sn-2 position (e.g. 2-3% 20:5, 0-0.6% 22:6) of triacylglycerols from rats fed the ester. We conclude that the chylomicron triacylglycerols arising via the 2-monoacylglycerol and the phosphatidic acid pathways differ mainly in the composition of the fatty acids in the sn-2 position. The similarity in the acids of the sn-1 and sn-3 positions of the chylomicron triacylglycerols from rats fed oil or ester is consistent with a hydrolysis of the acylglycerol products of the phosphatidic acid pathway to 2-monoacylglycerols prior to reconversion to triacylglycerols via the monoacylglycerol pathway and secretion as chylomicrons.

Animals↗
PubMed1990

Biological characterization of multidrug-resistant human colon carcinoma sublines induced/selected by two methods.

Two independent multidrug-resistant (MDR) sublines, AdR1.2 and SRA1.2, were developed from the established human colon carcinoma cell line LoVo. AdR1.2 was developed by a long-term continuous exposure of LoVo cells to Adriamycin in stepwise increments of concentration; SRA1.2 was selected/induced by pulse treatments by using a single concentration of Adriamycin. The two resistant sublines were cross-resistant and cross-sensitive to a similar spectrum of cytotoxic agents. However, AdR1.2 was most resistant to Adriamycin among the nine agents tested, and SRA1.2 was most resistant to Vinca alkaloids. Although SRA1.2 had biological characteristics similar to those of LoVo, AdR1.2 had remarkably altered biological properties, including no detectable carcinoembryonic antigen secretion, a smaller proportion of proliferating cells and a lower growth rate, lower fraction of cells in S phase, a lower colony-forming ability, and smaller colonies. In addition, the resistant phenotype of AdR1.2 was reversed when the cells were grown in a drug-free medium, whereas SRA1.2 maintained its resistance for at least 10 months under similar conditions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the plasma membrane proteins demonstrated overproduction of an Mr 130,000 protein in both the resistant sublines. The Mr 130,000 protein was not immunoreactive with C219 monoclonal antibody against p170, but the absence of Mr 130,000 protein in an AdR1.2 revertant and the parental LoVo suggests that it is an MDR-related plasma membrane protein. The absence of a 46-kDa cytosolic protein and the presence of a Mr 150,000 plasma membrane protein were found in AdR1.2 but not in SRA1.2. This Mr 150,000 protein immunoreacted with C219. This protein was also present, although in a reduced amount, in an AdR1.2 revertant that retained three times the MDR of LoVo cells and was thus comparable to SRA1.2. The two MDR sublines thus may represent two independent subclones which may serve as two different models for the study of multidrug resistance in human colon cancer.

Adenocarcinoma↗
PubMed1990

Surface array proteins of Campylobacter fetus block lectin-mediated binding to type A lipopolysaccharide.

Campylobacter fetus strains with type A lipopolysaccharide (LPS) and a surface array protein layer (S+) have been found to be pathogenic in humans and animals. Spontaneous laboratory mutants that lack surface array proteins (S-) are sensitive to the bactericidal activity of normal human serum. The ability of lectins to determine the presence of the S-layer and differentiate LPS type was assessed. We screened 14 lectins and found 3 (wheat germ agglutinin, Bandeiraea simplicifolia II, and Helix pomatia agglutinin) that agglutinated S- C. fetus strains with type A LPS but not S- strains with type B or type C LPS or S+ strains. However, the S+ type A strains were agglutinated after sequential water extraction, heat, or pronase treatment, all of which remove the S-layer, whereas there was no effect on the control strains. Specific carbohydrates for each lectin and purified LPS from a type A C. fetus strain specifically inhibited agglutination of an S- type A strain. In a direct enzyme-linked lectin assay, binding to the S- type A LPS strain was significantly greater than binding to the S+ strain (P = 0.01) or to a Campylobacter jejuni strain (P = 0.008). Consequently, these results indicate that the three lectins bind to the O side chains of C. fetus type A LPS but that the presence of the S-layer on intact cells blocks binding.

Agglutination Tests↗
PubMed1990

Intestinal absorption of menhaden and rapeseed oils and their fatty acid methyl and ethyl esters in the rat.

The relative cellular uptake and incorporation into prechylomicrons and chylomicrons was investigated for the menhaden and rapeseed oil fatty acids, when given by stomach tube as the original oils or the corresponding methyl and ethyl esters. The intermediates and final products of cellular acylation were determined by chromatographic methods at various times over a period of 1-24 h. There was little selectivity in the uptake among the oligo- and poly-unsaturated fatty acids of menhaden oil, when either oil or esters were fed. In contrast, the long-chain saturated and monounsaturated fatty acids of rapeseed oil were discriminated against during both cellular uptake and reacylation (60% overall reduction in utilization). Also, there was detectable discrimination against the long-chain polyunsaturated monoacylglycerols of menhaden oil and against the long-chain saturated and monounsatured monoacylglycerols of rapeseed oil during both cellular uptake and reacylation (30% overall reduction in utilization). Evidence was obtained for an indiscriminate cellular uptake of variable amounts (4-22%) of intact dietary methyl and ethyl esters of fatty acids, which, however, appeared in the chylomicrons only to a very limited extent (0.1-1.0% of total lipid). During peak absorption the cellular and lymphatic appearance of fatty acids from the digestion and absorption of the alkyl esters was nearly 50% lower than that from the corresponding triacylglycerols. The slower absorption of the fatty acids from the alkyl ester feeding is hypothetically attributed to a lower efficiency of the phosphatidic acid pathway, which is required in the absence of dietary 2-monoacylglycerols, but other mechanisms cannot be excluded.

Animals↗