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C Y Lau

Publications and source records attributed to C Y Lau.

49 records · Page 3Linked to original sources
PubMed1985

Graft-versus-host disease in murine bone marrow transplantation. II. Modulation of acute and chronic GVHD in mice receiving bone marrow allografts pretreated with immunosuppressive factor derived from a human T cell line.

BALB/c bone marrow treated with monoclonal anti-Thy 1.2 antibody and complement is unable to produce prolonged hemopoietic repopulation and survival when transplanted to lethally-irradiated allogeneic CBA recipient mice. Preincubation of the antibody treated bone marrow cells with an immunosuppressive factor (SAF) derived from a 6-thioguanine resistant cell line, itself derived from the human T cell line CEM, in contrast, allowed those bone marrow cells to produce a state of chimerism and long term survival. Parameters designed to gauge the degree of graft-versus-host reactivity (GVHR) in these animals suggested that acute GVHR was abolished with this procedure. Moreover, defining chronic GVHD as associated with abnormally high spontaneous proliferation of splenic cells, elevated anti-host mixed lymphocyte reactivity, or elevated serum immunoglobulin levels (in all cases when compared with the syngeneically repopulated BALB/c----BALB/c), our data suggest that preincubation with SAF modified chronic GVHD also.

Acute Disease↗
PubMed1985

Mechanism of action of a suppressor-activating factor (SAF) produced by a human T cell line.

We previously described a potent suppressor-activating factor (SAF) produced constitutively by a 6-thioguanine-resistant mutant of the human T cell line CEM. In the present study, we investigated the mechanism of action of SAF. After a brief (4- to 18-hr) exposure to SAF at 37 degrees C, T lymphocytes (either unseparated, or purified OKT4+ and OKT8+ subpopulations), but not B lymphocytes, suppressed allogeneic and syngeneic T cells in co-culture experiments, apparently via the release of a suppressor activity. The total T cell-released suppressor activity (TRSA) accumulated after 3 days culture post-treatment was about 100- to 500-fold higher than the original suppressor activity (SAF) added to trigger the release. Arresting protein or DNA synthesis, or even killing the cells did not affect the release of TRSA by T lymphocytes, but lowering the incubation temperature to 4 degrees C reduced it drastically. Pre-treatment of T lymphocytes with the metabolic inhibitor, sodium azide, or the adenylate cyclase stimulator, prostaglandin E2, or the addition of exogenous dibutyryl cAMP, all suppressed the release of TRSA. The presence of monoclonal antibody OKT3, but not OKT4 or OKT8, enhanced the release of TRSA. The presence of OKT11 blocked the release of SAF. The functional characteristics of TRSA appeared to be identical to those of SAF. However, unlike SAF, interaction of T lymphocytes with TRSA triggered only marginal enhancement of suppressor activity. In addition, the kinetics of the suppression mediated by SAF showed a much larger increment as a function of time than that mediated by TRSA. Taken together, the data suggest that SAF might represent an activated form of SAF, and that the continuous activation of SAF by lymphocytes in culture may account for its high potency in suppressing T cell proliferation in vitro.

Binding Sites↗
PubMed1984

A mutant human T-cell line producing immunosuppressive factor(s).

6T-CEM-20, a subclone of a 6-thioguanine-resistant mutant derived from the human-T-cell line CEM, secreted into the medium, a high titered immunosuppressive factor specific for T cells. The cell-free supernatant was very potent in suppressing, via a noncytotoxic mechanism, mitogen-activated T-cell proliferation, cytotoxic T-cell functions, and pokeweed mitogen (PWM)-stimulated plaque-forming cells (PFC). Lower dilutions of the supernatant (10(-1)-10(-2] abrogated T-cell functions within 24 hr whereas higher dilutions (10(-3)-10(-7] required a culture period of up to 4 days with lymphocytes to arrest T-cell activities. The suppressive activity was most pronounced when the factor was added in the early part of the culture period. The factor was sensitive to heat treatment and both low and high pH (most stable at physiological pH). Preliminary purification with column chromatography indicates that the active moiety was contained in the high-molecular-weight fraction (MW greater than 200,000). Data from coculture experiments suggested that T lymphocytes, which were exposed for 5-12 hr to the active supernatant or the partially purified material, suppressed allogeneic T-cell proliferation in a dose-related manner. This suppressor factor which we called suppressor-activating factor (SAF) might have activated a suppressor population or induced the production of a suppressor factor which in turn mediated the observed suppression. Both the molecular structure and the detailed mechanism of action are under investigation.

B-Lymphocytes↗
PubMed1980

Functional effects of thymopoietin32-36 (TP5) on cytotoxic lymphocyte precursor units (CLP-U). I. Enhancement of splenic CLP-U in vitro and in vivo after suboptimal antigenic stimulation.

Cytotoxic lymphocyte precursor units (CLP-U) were enumerated in the spleens of C57BL/6 mice 3 days after i.p. injections of synthetic thymopoietin32-36 (TP5). One hundred to 1000 ng TP5/mouse potentiated splenic CLP-U, this effect being detectable only after suboptimal allogeneic sensitization (with 1.2 x 10(5) mitomycin-C treated DBA cells). This elevation of CLP-U persisted in the injected mice for at least 14 days. Control peptide did not affect CLP-U. In vitro incubation of 0.01 to 0.1 ng/ml of TP5 with normal C57BL/6 spleen cells also enhanced CLP-U after suboptimal allogeneic stimulation; high concentrations of TP5 caused suppression of CLP-U and this was detectable with optimal sensitization conditions. Thus TP5, in vitro and in vivo, appears to regulate immune responsiveness and this regulation varies with TP5 dosage and with the immune stimulus.

Animals↗
PubMed1980

Effect of thymopoietin pentapeptide (TP5) on autoimmunity. I. TP5 suppression of induced erythrocyte autoantibodies in C3H mice.

C3H mice (young and old), when immunized with the cross-reacting rat erythrocytes, produced erythrocyte autoantibodies that usually persisted for more than 10 weeks. I.P. injection of thymopoietin pentapeptide (TP5) once or thrice weekly accelerated the loss of erythrocyte autoantibodies 7 weeks after immunization; 10 ng of TP5 was the optimal dose. The rat agglutinin responses of these immunized mice were unaffected by TP5 during the whole period of study. Spleen cells from rat erythrocyte-immunized mice, when transferred to syngeneic recipients undergoing similar immunization schedules, delayed the appearance of erythrocyte autoantibodies in the recipients. A greater delay was observed when spleen cells were taken from mice that had also received TP5 treatment.

Agglutinins↗
PubMed1979

In vitro differentiation of B lymphocytes from pre-B cells.

Adult bone marrow contains both B lymphocytes and their immediate precursors, pre-B cells. These two cells differ in size and can be separated by velocity sedimentation; B cells are enriched in the subpopulation of cells sedimenting at between 2.0 and 3.5 mm/hr and pre-B cells in the subpopulation between 5.0 and 7.0 mm/hr. Incubation of pre-B cells in vitro for 4 or 5 days leads to their differentiation into functional B lymphocytes. The transition form pre-B to B appears to occur in two steps. The first step gives mitogen responsive B cells with an intermediate sedimentation velocity and the second step produces typical small, slowly sedimenting B cells. Pre-B cells can be quantified by using a limiting dilution assay and occur at a frequency of 1/60 in the subpopulation of rapidly sedimenting bone marrow cells.

Animals↗
PubMedDate not supplied

Role of aldehyde dehydrogenase in the biological activity of spermine dialdehyde, a novel immunosuppressive/purging agent.

The antitumour and immunosuppressive activities of spermine dialdehyde (SDA), a synthetic, oxidized form of spermine, were examined using L1210 cell lines and murine bone marrow cells. SDA acted as a high affinity substrate for aldehyde dehydrogenase (ADH) derived from different sources, with kinetic profiles similar to other aldehyde substrates. The murine leukaemic, cyclophosphamide-resistant L1210/CPA cells, having high levels of intracellular ADH activity, were less sensitive to SDA compared to ADH deficient L1210/O cells as measured by [3H]-thymidine incorporation in proliferation studies. Furthermore, pretreatment of L1210/CPA cells with the ADH inhibitor, diethyl aminobenzaldehyde (DEAB), resulted in potentiation of the SDA response. Murine bone marrow cells were more resistant to SDA than splenic T cells. However, addition of DEAB to bone marrow cultures potentiated the sensitivity of progenitor cells to SDA, as measured by colony formation. The results indicate that levels of ADH in the target tissues would determine the potency of SDA and subsequently offer selectivity and specificity to the therapeutic potentials of this putative purging agent.

Aldehyde Dehydrogenase↗
PubMedDate not supplied

Recombinant human platelet-derived growth factor-BB (becaplermin) for healing chronic lower extremity diabetic ulcers: an open-label clinical evaluation of efficacy.

Topically applied recombinant human platelet-derived growth factor-BB (becaplermin) is a new pharmacologically active therapy for chronic, neuropathic, lower extremity diabetic ulcers. In previous studies, becaplermin gel was administered once daily but dressings were changed twice daily. In the present study of 134 patients with diabetes mellitus and full thickness lower extremity ulcers, dressings were changed only once per day, simplifying the treatment regimen. Efficacy criteria included the percentage of patients achieving complete healing within the 20-week treatment period, the time to achieve complete healing, the rate of ulcer recurrence during the 6-month period following healing, and treatment compliance. Complete healing of ulcers was achieved in 57. 5% of patients, with a mean time to closure of 63 days and a recurrence rate of 21% at 6 months. Of the potential factors affecting ulcer healing, only drug compliance (p < 0.001), dressing compliance (p < 0.01), the presence of infection (p < 0.01), baseline ulcer area (p < 0.05), and baseline total wound evaluation score (p < 0.05) were significantly associated with healing. Results of this study further confirm the efficacy and safety of becaplermin gel for the treatment of lower extremity diabetic ulcers.

Becaplermin↗
PubMedDate not supplied

Evaluation of epoetin alpha (rHuEPO) and darbepoetin alpha (DARB) on human burst-colony formation (BFU-E) in culture.

The erythropoietic effect of recombinant human erythropoietin, epoetin alpha (rHuEPO), in promoting the growth of erythroid burst-forming units (BFU-E) was compared with darbepoetin alpha (DARB), a rHuEPO analogue obtained by site-directed mutagenesis. Human bone marrow cells derived from healthy donors were cultured with different concentrations of rHuEPO or DARB for 12 - 21 days and BFU-E were counted using an inverted microscope. The EC50 of rHuEPO was about 10-fold lower than DARB and the size of the colonies was significantly larger in rHuEPO-containing cultures using comparable concentrations. The maximum number of colonies obtained in some rHuEPO-containing cultures was also higher than for DARB. The number of colonies in DARB-containing cultures was increased, in part, by the addition of low concentrations of rHuEPO, but not by DARB, even at high concentrations. We conclude that DARB is not as effective as rHuEPO in supporting the in vitro growth of human BFU-E.

Bone Marrow Cells↗
PubMedDate not supplied

Association between glycaemic control and quality of life in diabetes mellitus.

BACKGROUND: Relationship between quality of life (QOL) and haemoglobin A1c (HbA1c) amongst diabetics in the community setting is unclear. AIMS: Assess the association between QOL and change in HbA1c in diabetic patients over one year. SETTINGS AND DESIGN: Cohort study of patients from four community clinics in California, USA. METHODS: Diabetic patients identified from databases using International Classification of Disease (ICD-9) codes were asked to complete Short Form 36 (SF-36), which measures health-related QOL, and invited to attend monthly diabetes workshops. From December 2000 to December 2001, data were collected on multiple parameters, including HbA1c. SF-36 surveys were re-collected at project termination. STATISTICAL ANALYSIS: Regression analysis was used to correlate change in HbA1c with change in QOL physical component summary (PCS) and mental component summary (MCS) scores, while considering potential confounders. RESULTS: Of 1679 eligible patients, 380 completed SF-36 at project initiation. 243 of those completed SF-36 at project termination. Pre and post HbA1c data were available for 170 of the 243 who completed SF-36 at both times. Average MCS increased by 8.46% and PCS decreased by 2.24%. After adjustment, a 5% decrease in HbA1c values was associated with a 1% increase in MCS. No association between changes in HbA1c and PCS was observed. CONCLUSIONS: Association between better HbA1c and improved mental, but not physical, QOL may reflect physical inconvenience of increased regimen complexity and mental empowerment from proactive disease management. Larger cohort studies with longer follow-up are needed to further elucidate the relationship between glycemic control and QOL.

Cohort Studies↗