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Biomedical subjects

T F Yu

Publications and source records attributed to T F Yu.

At least 19 recordsLinked to original sources
PubMed1998

CTLA-4 blockade synergizes with tumor-derived granulocyte-macrophage colony-stimulating factor for treatment of an experimental mammary carcinoma.

Generation of a T cell-mediated antitumor response depends on T cell receptor engagement by major histocompatibility complex/antigen as well as CD28 ligation by B7. CTLA-4 is a second B7 receptor expressed by T cells upon activation that, unlike CD28, appears to deliver an inhibitory signal to T cells. Recently, we and others demonstrated that administration of an anti-CTLA-4 antibody was sufficient to promote regression of several murine tumors. However, certain tumors, such as the SM1 mammary carcinoma, remain refractory to this type of immunotherapy. In the present study, we report that the combination of both CTLA-4 blockade and a vaccine consisting of granulocyte-macrophage colony-stimulating factor-expressing SM1 cells resulted in regression of parental SM1 tumors, despite the ineffectiveness of either treatment alone. This synergistic therapy resulted in long-lasting immunity to SM1 and depended on both CD4(+) and CD8(+) T cells. Interestingly, synergy was not observed between CTLA-4 and a B7-expressing SM1 vaccine. Given that granulocyte-macrophage colony-stimulating factor promotes differentiation and activation of dendritic cells as well as enhances cross-priming of T cells to tumor-derived antigens and that SM1 is major histocompatibility complex class II-negative, our findings suggest that CTLA-4 blockade acts at the level of a host-derived antigen-presenting cell. In addition, these results also support the idea that the most effective and synergistic vaccine strategy targets treatments that enhance T cell priming at the level of host-derived antigen-presenting cells.

Abatacept↗
PubMed1998

Enhancement of the anti-tumor immune response using a combination of interferon-gamma and B7 expression in an experimental mammary carcinoma.

In recent years, tumor immunotherapy has begun to exploit the emerging knowledge of the mechanisms of T cell activation to enhance the immune responses to tumors. However, many tumors, despite genetic modification to express co-stimulatory molecules or cytokines, are not readily rejected due to their inherently poor immunogenicity. In the present study, we tested whether expression of the co-stimulatory ligand B7-1 and the immunostimulatory cytokines interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary carcinoma (SM1) would sufficiently augment its immunogenicity to obtain rejection and immunity. Our findings demonstrate that expression of B7, IFN-gamma, or GM-CSF alone, or co-expression of B7 and GM-CSF did not result in rejection of SM1. However, co-expression of B7 and IFN-gamma was sufficient to result in regression of SM1 tumors by a CD8+ T cell-dependent mechanism. Rejection of the B7/IFN-gamma-expressing SM1 tumor resulted in protection from rechallenge not only with the unmodified SM1 tumor but with another syngeneic mammary tumor. Our data support the idea that although B7 expression alone may not be sufficient for rejection of certain tumors, the immune system may be stimulated to mount an effective anti-tumor immune response by the co-expression of both the co-stimulatory ligand and a cytokine.

Animals↗
PubMed1996

Purification and characterization of lupus anticoagulant like protein from Agkistrodon halys brevicaudus venom.

By means of CM-Sephadex C-25, DEAE-Sephadex A-50, Sephadex G-200, and Sephadex G-75 chromatographies, a lupus anticoagulant like protein (LALP) from Agkistrodon halys brevicaudus was purified. On SDS-PAGE, the purified LALP had a molecular weight of 25,500 daltons under non-reducing condition and 15,000 daltons under reducing condition. The isoelectric point was pH 5.6. Its N terminal amino acid sequencing revealed a mixture of 2 sequences: DCP(P/S)(D/G)WSSYEGH(C/R)(Q/K). It was devoid of phospholipase A, fibrino(geno)lytic, 5'-nucleotidase, L-amino acid oxidase, phosphomonoesterase, phosphodiesterase and thrombin-like activities, which were found in crude venom. In the presence of LALP, PT, aPTT, and dRVVT of human plasma were markedly prolonged and its effects were concentration-dependent but time-independent. The inhibitory effect of LALP on the plasma clotting time was enhanced by decreasing phospholipid concentration in TTI test. The individual clotting factor activity was not affected by LALP when higher dilutions of LALP-plasma mixture were used for assay. Russell's viper venom time was shortened when high phospholipid confirmatory reagent was used. Therefore, the protein has lupus anticoagulant property.

Agkistrodon↗
PubMed1994

Purification and characterization of L-amino acid oxidase from king cobra (Ophiophagus hannah) venom and its effects on human platelet aggregation.

Venoms of several snake species contain large amounts of L-amino acid oxidase but its effects on human plasma coagulation and platelet aggregation have not been explored. We have purified L-amino acid oxidase from king cobra venom through CM-Sephadex C-25, Sephadex G-100 and DEAE Sephadex A-50 chromatographies. The purified enzyme has a mol. wt of 135,000 as determined by gel filtration and 65,000 by SDS-PAGE under non-reducing and reducing conditions. Incubation of plasma with L-amino acid oxidase at 200 micrograms/ml did not affect prothrombin time, activated partial thromboplastin time, or thrombin time. Upon addition of L-amino acid oxidase, platelets in platelet-rich plasma were aggregated. The enzyme-induced aggregation was abolished by catalase. The aggregation was also inhibited by indomethacin, aspirin, ethylenediaminetetraacetate, sodium nitroprusside, prostaglandin E1, mepacrine and verapamil, but not by heparin, hirudin, creatine phosphate/creatine phosphokinase or antimycin/2-deoxy-D-glucose. These results suggest that L-amino acid oxidase induces human platelet aggregation through the formation of H2O2, and subsequent thromboxane A2 synthesis requiring Ca2+ but independent of ADP release. The platelet aggregation caused by L-amino acid oxidase is likely to contribute to toxicity inflicted by cobra venom.

Alprostadil↗
PubMed1989

Lipid studies in primary gout.

Serum total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride were measured in three groups of male patients with primary gout. The groups were defined by the presence of 0, 1, or more than 1 coexisting medical conditions or cardiac risk factors (coronary heart disease, hypertension, diabetes, proteinuria, overweight). Mean values of total, LDL, and HDL cholesterol were lower in patients with one or more associated conditions than in those with none. By contrast, triglyceride levels were significantly higher and exceeded the desirable range. Distributions of individual values of all lipid parameters except triglycerides were similar along the three groups. Triglyceride values, however, were significantly higher in patients with multiple complications. Observed differences in lipid values could not be correlated with patient age or type of nature of medication received. High triglycerides and LDL cholesterol are not a feature of uncomplicated gout in men. HDL cholesterol tends to be normal and triglyceride mildly elevated. Only in patients with two or three associated medical conditions are high triglycerides or low HDL cholesterol common. Our results suggest that these findings are independently related to concurrent disease and that gout is not necessarily in itself a risk factor for cardiovascular or diabetic disease.

Adult↗
PubMed1986

Impact of associated medical conditions on clinical features of gout.

In view of the various available drugs, we are now in a very much better situation for treatment of gout, with and without associated medical conditions. When several drugs are employed in one single patient, however, one may run into drug interactions, resulting into exaggerated hyperuricemia or induced acute gouty arthritis. In lieu of the various associated medical conditions, controlled or uncontrolled, the clinical features of gout may be modified. Accordingly, one must treat the patient's gout as well as his various stages of the associated medical conditions, and each patient must be individualized.

Adult↗
PubMed1984

Studies on the metabolism of D-penicillamine and its interaction with probenecid in cystinuria and rheumatoid arthritis.

Four patients with recurrent cystine stones and 5 with rheumatoid arthritis (RA) were studied. After a single dose of D-penicillamine to cystinuric patients, cystine excretion decreased considerably. Cysteine-penicillamine mixed disulfide (CSSP) and penicillamine disulfide (PSSP) metabolites appeared within 1-2 h (CSSP/PSSP approximately equal to 4.8-8.6). In RA, cystine excretion remained negligible (CSSP/PSSP approximately equal to 1.4-2.9). With daily D-penicillamine in RA (CSSP/PSSP ratios were usually greater than 7 in those with favorable clinical response. CSSP/PSSP ratios may help to predict prognosis and adjust penicillamine dosage. Coadministration of probenecid is contraindicated in hyperuricemic cystinuric patients because of increased cystine and decreased CSSP and PSSP excretion.

Arthritis, Rheumatoid↗
PubMed1981

Long-term follow-up of incorporation of 15N from glycine into uric acid in gout.

The incorporation of 15N-glycine into urinary uric acid was studied in three gouty patients, repeating a study carried out 13 to 27 years ago. The 15N incorporation attained a lower maximum and declined less rapidly in the repeat study in all three patients. The cumulative 15N incorporation into uric acid was reduced to one half of that determined previously. Similarly, urinary uric acid excretion was less, along with a lower uric acid nitrogen to total nitrogen ratio. The data indicate changes in the nature of the metabolic aberrations, which are apparently related to long-term drug therapy, changes in lifestyle, aging and associated medical complications.

Adult↗
PubMed1980

A radiologic reevaluation of gout: a study of 2,000 patients.

Radiographs were available for study for 466 of 2,000 patients with primary gout who were followed clinically for as long as 30 years. The radiographic manifestations at various stages of the disease and the effect of therapy were studied in 80 patients. New radiographic signs, such as lace pattern, intracortical lesions, and subchondral compressions, are emphasized as well as the frequency of tophaceous lesions affecting the dorsum of the feet.

Arthrography↗
PubMed1976

Pharmacokinetic and clinical studies of a new uricosuric agent - benzbromarone.

Benzbromarone, a potent uricosuric agent, is a benzofuran derivative with a bromine on the 3rd and 5th positions of the benzene ring. Readily absorbed after oral administration, it is promptly dehalogenated in the liver and excreted via the biliary system. Peak drug concentration usually precedes maximal uricosuria following a single dose of 40 mg of benzbromarone, since benzarone, one of the two metabolites, likewise has a uricosuric action. Longterm studies in 24 gouty patients indicate that the drug is well tolerated. It has not produced any skin rash or renal colic. Renal hemodynamics, blood picture, and liver enzymes were unchanged. Since it is eliminated by the biliary tract, it may cause diarrhoea in some patients. Being a very potent uricosuric agent, it is not advocated in patients with a history of uric acid lithiasis. The uricosuric effect is not liable to be counteracted when used in conjunction with hyperuricemic diuretics. The drug is particularly useful in patients with chronic gouty arthritis and tophi, either refractory or allergic to probenecid, sulfinpyrazone, or allopurinol.

Adult↗