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Biomedical subjects

M Y Yu

Publications and source records attributed to M Y Yu.

At least 73 records · Page 4Linked to original sources
PubMed1991

Expression and characterization of the preS1 peptide of hepatitis B surface antigen in Escherichia coli.

The infectious particles of hepatitis B virus (HBV) contain 3 related surface antigens, i.e., small, medium, and large, all of which are encoded by one large open reading frame with multiple initiation codons. The large surface antigen (L-Ag) contains preS1, preS2, and S regions while both the middle and small surface antigens lack preS1. Several lines of evidence suggested that the preS1 region is involved in the binding of HBV to human hepatocytes as shown by its binding to HepG2 cells and isolated human hepatocyte membranes. To obtain large quantity of preS1 peptide, an expression vector was constructed containing a lac promoter, the 5' half of the beta-galactosidase gene, the Factor Xa tetrapeptide recognition sequence, and the coding region of preS1 plus preS2. This recombinant plasmid constitutively produced high concentration of a fusion protein in inclusion bodies in Escherichia coli. When the fusion protein was treated with Factor Xa, a peptide consisting of the N-terminal 91 amino acids of the preS1 region was released. This preS1 fragment purified by anion exchange chromatography was able to bind specifically to the isolated plasma membranes from human liver. Hence, this recombinant preS1 peptide can be used to identify and isolate hepatocyte receptors for HBV.

Base Sequence↗
PubMed1991

Significance of pre-S2 protein and its antibody in children with HBV infections.

Pre-S2 protein and its antibody were detected in 130 children with hepatitis B virus (HBV) infection and 30 with T6 hepatitis B (HB) vaccination. The results showed that pre-S2 was positive in most chronic persistent hepatitis (CPH) and chronic active hepatitis(CAH) patients, while anti-pre-S2 was positive in only 8% (2/92 cases) and 11.5% (3/26 cases) respectively. The positive rate of anti-pre-S2 was 78.9% (15/19 cases) in cases at the convalescent stage of acute hepatitis B, 91.7% (55/60 cases) in cases with T6 HB vaccination and 83.3% (25.30 cases) in naturally acquired anti-HBs children, while pre-S2 was not noted. Anti-pre-S2 was negatively related to ALT and positively to anti-HBs (P less than 0.01). The positive relation of pre-S2 to HBsAg was observed. These results suggest that pre-S2 could be a marker for HBV infection, and anti-pre-S2 may indicate a favourable prognosis of HBV infection. There was no correlation between anti-pre-S2 and pathogenic damages induced by HBV.

Adolescent↗
PubMed1990

Hepatitis B virus propagated in a rat hepatoma cell line is infectious in a primate model.

The human hepatitis B virus (HBV) produced by a rat hepatoma cell line through transfection with HBV DNA is infectious in the human primate model--chimpanzee. Since hepadnaviruses are known to have an extremely narrow host range, our results support the idea that the host species barrier of HBV infection resides on the penetration/adsorption step rather than any postpenetration intracellular event during the virus life cycle.

Animals↗
PubMed1989

In vivo distribution of adoptively transferred indium-111-labeled tumor infiltrating lymphocytes and peripheral blood lymphocytes in patients with metastatic melanoma.

Patients with metastatic melanoma undergoing therapy with cyclophosphamide (CPM), tumor-infiltrating lymphocytes (TIL), and interleukin-2 (IL-2) were studied for the ability of their 111In-labeled TIL or peripheral blood lymphocytes (PBL) to localize in sites of tumor using gamma camera imaging and biopsies. Nineteen infusions of radiolabeled TIL were given to 18 patients, while five patients received radiolabeled autologous PBL during TIL therapy. Clear tumor localization was seen on 13 of 18 nuclear scan series performed on 111In-TIL recipients, while tumor was imaged in only one of four scan sequences on patients given 111In-PBL. Nineteen paired biopsies of tumor and normal skin were completed on 10 patients receiving 111In-TIL, while eight biopsies were done on three PBL patients receiving 111In-PBL. The mean percentage of total injectate activity localizing per gram of tumor tissue was 0.0049% in the TIL group and 0.0010% in the PBL group (P2 = .0004). The mean of the tumor to normal skin ratios of the 111In-TIL group was three times that for 111In-PBL (P2 = .0072). One patient was studied by nuclear scanning on three consecutive treatment courses of CPM, TIL, and IL-2. He initially demonstrated clear tumor localization by 111In-TIL at several sites, then faint localization with 111In-PBL at a single site, and subsequently positive tumor imaging on repeat 111In-TIL infusion at multiple sites. These results confirm and expand our initial data demonstrating that human TIL transferred with CPM pretreatment and followed by IL-2 preferentially localize to tumor sites and indicate that this localization is greater for TIL than PBL.

Adult↗
PubMed1989

Characterization of von Willebrand factor in factor VIII concentrates.

Commercial concentrates of factor VIII (FVIII) were analyzed in order to 1) determine the effects of viral inactivation on von Willebrand factor (vWF); 2) evaluate the vWF content of the new, immunopurified concentrates; and 3) assess their potential for correcting the long bleeding time of von Willebrand disease (vWD). Included in our study were products that had been treated to inactivate viruses; older, untreated products; and the new, immunopurified concentrates. We measured von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (RCoF), and vWF multimeric and subunit composition. A newly developed radioimmunoassay (RIA) was used to quantitate vWF:Ag. The vWF:Ag content varied from 0.083 micrograms/IU FVIII:C for Hemofil M to 32.2 micrograms/IU FVIII:C for Humate-P, whereas pooled normal human plasma (NHP) contained 6.3 micrograms/IU FVIII:C. The RCoF varied from 0.0007 to 2.09 U/IU FVIII:C, with the immunopurified concentrates having the lowest values and Humate-P the highest. The ratio of RCoF to vWF:Ag ranged from 11 to 96 U/mg, as compared to a ratio of 160 for NHP. All of the concentrates lacked the largest vWF multimers, and all had abnormal triplet patterns. Modest differences between some untreated concentrates and their treated counterparts were noted. As expected, the immunopurified concentrates had much lower levels of all vWF activities than the conventionally prepared products. Our data suggest that none of the concentrates have as great a capacity as NHP to correct the prolonged bleeding time of von Willebrand disease.

Antigens↗
PubMed1984

Immunosuppression by cytostatic drugs?

In the present study, an attempt was made to characterize the immunomodulating abilities of the cytostatic drugs cyclophosphamide, ifosfamide, vinblastine, vincristine, procarbazine, dacarbazine, 6-mercaptopurine, methotrexate, 5-fluorouracil and adriamycin in a defined experimental model. Varying combinations of drug plus transplantation alloantigen, (C3H-lymphocytes) were injected into Balb/c mice at different time intervals in vivo. The resulting T-effector cell reactivity was determined in vitro with the microcytotoxicity assay on day +5 for primary (1 degree) and day +7 for secondary (2 degrees) sensitized mice. According to the type of drug (alkylating agent vs. vinca alkaloid vs. antimetabolite vs. cytostatic antibiotic), the dosage (20% LD50 vs. 60% LD50), the state of sensitization (1 degree vs. 2 degrees sensitized recipients), and the time of drug application in relation to the antigen treatment on day 0 (in varying steps from day -6 to day +4), so-called "pharmacon-antigen-variation-effects" (PAVE) were established for each of the investigated drugs in form of reaction profiles. The results were as follows: For almost all substances, characteristic reaction profiles involving immunostimulation and/or immunosuppression could be established. Similarities in the profiles of different substances made it possible to classify the drugs according to different reaction types. The reaction type however is not definitely correlated to the biochemical mechanism of drug action. The PAVE are decisively influenced by some of the biological parameters, such as the time of drug application in relation to the antigen treatment and the state of sensitization but relatively little by the dosage of the drug. Considering the different processes occurring during primary and secondary immune responses, the PAVE may give hints for a distinct manipulation of the immunoregulation and thus information on the immunobiological mechanism of drug action.

Animals↗
PubMed1982

Effects of 12-0-Tetradecanoylphorbol-13-acetate (TPA) on rat pheochromocytoma (PC12) cells: interactions with epidermal growth factor and nerve growth factor.

The phorbol ester tumor promotor 12-0-tetradecanoylphorbol-13-acetate (TPA) specifically inhibited the binding of radioiodinated epidermal growth factor (125I-EGF) to rat pheochromocytoma (PC12) cells in a noncompetitive fashion with an apparent Ki of 11-26 nM. Both TPA and EGF elicited similar biological responses in PC12 cells including enhanced incorporation of 3H-choline and 32 P-orthophosphate into macromolecules, induction of ornithine decarboxylase, and stimulation of the phosphorylation of a 30,000 MW nonhistone, chromosome-associated protein. These effects were also elicited by nerve growth fact (NGF) which, in contrast to the former agents, is a differentiating stimulus for PC12 cells. The effects of TPA were additive or more than additive to the effects of NGF and EGF. When PC12 cells were induced to differentiate by treatment with NGF for 72 hours, the binding of 125I-EGF and responses to EGF were reduced by approximately 70%. The response of PC12 cells to the tumor promoter TPA was unaffected by treatment with NGF. Thus, the qualitatively similar effects of TPA and EGF seemed to be mediated through separate receptor systems with only the EGF receptor system reduced by NGF treatment.

Animals↗
PubMed1976

Control of adenylate cyclase from secretory vesicle membranes by beta-adrenergic agents and nerve growth factor.

Adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity of purified secretory vesicle membranes from the adrenal medulla is inhibited by I-isoproterenol and I-epinephrine, as well as by nerve growth factor (NGF). The effect of these agents was found to be dose-dependent and, in the case of the catecholamines, saturable. NGF was active at concentrations as low as 10(-8) M. Oxidized NGF was only minimally active, and insulin was completely inactive. Neither dopamine nor phenylephrine had activity. Inhibition of cyclase by either isoproterenol or epinephrine was blocked by I-propranolol, a specific beta-antagonist, but propranolol by itself had no effect on adenylate cyclase activity. The data indicate that the secretory vesicle membrane has beta-adrenergic receptors coupled to the adenylate cyclase. Propranolol was also found to block the NGF-induced inhibition of cyclase. We conclude that the granule membrane has beta-adrenergic receptors as well as NGF-reactive sites, and that the two may be functionally linked.

Adenylyl Cyclase Inhibitors↗