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Biomedical subjects

P Tan

Publications and source records attributed to P Tan.

At least 19 recordsLinked to original sources
PubMed1992

Coexpression and functional cooperation of CTLA-4 and CD28 on activated T lymphocytes.

T cell costimulation by molecules on the antigen presenting cell (APC) is required for optimal T cell proliferation. The B7 molecule on APC binds the T lymphocyte receptor CD28, triggering increased interleukin 2 (IL-2) production and subsequent T cell proliferation. CTLA-4 is a predicted T cell membrane receptor homologous to CD28, which also binds the B7 counter receptor, but whose distribution and function are unknown. Here we have developed monoclonal antibodies (mAbs) specific for CTLA-4 and have investigated these questions. mAbs were produced that bound CTLA-4 but not CD28, and that blocked binding of CTLA-4 to B7. CTLA-4 expression as measured by these mAbs was virtually undetectable on resting T cells, but was increased several hundred-fold during T cell activation. On activated lymphocytes, CTLA-4 was expressed equally on CD4+ and CD8+ T cell subsets and was coexpressed with CD25, CD28, and CD45RO. CTLA-4 expression was lower than that of CD28, reaching a maximum of approximately 1/30-50 the level of CD28. Despite its lower expression, CTLA-4 was responsible for much of the B7 binding by large activated T cells. Anti-CTLA-4 mAb 11D4 and anti-CD28 mAb 9.3 acted cooperatively to inhibit T cell adhesion to B7, and to block T cell proliferation in primary mixed lymphocyte culture. When coimmobilized with anti T cell receptor (TCR) mAb, anti-CTLA-4 mAbs were less effective than anti-CD28 mAb 9.3 at costimulating proliferation of resting or activated T cells. However, coimmobilized combinations of anti-CD28 and anti-CTLA-4 were synergistic in their ability to augment anti-TCR-induced proliferation of preactivated CD4+ T cells. These results indicate that CTLA-4 is coexpressed with CD28 on activated T lymphocytes and cooperatively regulates T cell adhesion and activation by B7.

Abatacept↗
PubMed1992

Assessment of the molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil against Oncomelania hupensis.

Molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil were evaluated in the laboratory and the field against Oncomelania hupensis, the intermediate host of Schistosoma japonicum in China. The three chemicals were very effective against O. hupensis in the laboratory. The molluscicidal activities found in the field trials suggest that Tribromosalan and Cartap may be used as practical molluscicides. Dosage of 10 g/m2 of Tribromosalan in spring only and 20 g/m2 of Cartap in both spring and autumn would be recommendable as practical mollusciciding doses for the control of O. hupensis.

Animals↗
PubMed1992

Skin necrosis, a rare complication of coumarin therapy.

Coumarin congeners are frequently being prescribed in vascular surgery. The complication most often seen in haemorrhage. A less known complication is necrosis of skin and soft tissues. This rare complication is potentially lethal. The etiology is unclear, a relation with protein C deficiency seems likely. Early treatment with vitamin K and heparin may prevent the skin necrosis. After necrosis has occurred, surgical intervention is usually necessary.

Aged↗
PubMed1992

[Structure of swertiapuniside from Swertia punicea Hemsl].

A new xanthone glycoside, swertiapuniside (V), has been isolated from the whole plant of Swertia punicea Hemsl. The structure was elucidated as 1,5,8-trihydroxy-3-methoxyxanthone-8-O-beta-D-glucopyranosyl (1-6)-O-beta-D-glucopyranoside by means of chemical and spectroscopic data. Four other known xanthones mangiferin (I), bellidifodin (II), 1,3,5,8-tetrahydroxyxanthone (III) and swertinolin (IV) were also identified.

Drugs, Chinese Herbal↗
PubMed1991

Inhibition by brefeldin A of protein secretion from the apical cell surface of Madin-Darby canine kidney cells.

The effect of brefeldin A (BFA) on total and polarized protein secretion was examined in MDCK cells. Increasing concentrations of BFA have increasingly inhibitory effects on total protein secretion. The total protein secretion was essentially unaffected by BFA at 0.5 microgram/ml. When the BFA concentration was increased to 10 and 30 micrograms/ml, the total protein secretion was reduced to about 70 and 25%, respectively, of the control level. Consistent with this effect on total protein secretion, the Golgi structure as revealed by C6-NBD-ceramide (a fluorescent ceramide analog) staining was essentially unaltered by 0.5 microgram/ml BFA, while 10 and 30 micrograms/ml BFA significantly dispersed the Golgi apparatus. When the polarity of protein secretion was examined, it was found that the ratio of proteins secreted from the apical to those from the basolateral surface was reduced from 1.5-2.0 to 0.4-0.7 by all three BFA concentrations. Furthermore, several proteins which are preferentially released from the apical surface were found to be released without apparent surface polarity, while several other proteins which were preferentially released from the basolateral surface were unaffected. This study suggests that BFA, at 0.5 microgram/ml, can selectively inhibit protein secretion from the apical surface without affecting total protein secretion. The inhibition of apical secretion results in enhanced protein secretion from the basolateral surface.

4-Chloro-7-nitrobenzofurazan↗
PubMed1991

Disposition of propofol at caesarean section and in the postpartum period.

We have compared the pharmacokinetics of a bolus dose of propofol 2 mg kg-1 in eight patients undergoing Caesarean section with those in eight postpartum patients undergoing sterilization by mini-laparotomy. The Caesarean section group had a total body clearance of (median) 31.5 (range 24.4-53.3) ml min-1 kg-1, apparent volume of distribution at steady state 5.10 (2.46-6.61) litre kg-1 and mean residence time 161 (52.3-251) min; values for the post-partum group were 33.8 (21.5-47.2) ml min-1 kg-1, 5.17 (3.47-8.09) litre kg-1 and 163 (92.3-238) min, respectively. The 95% confidence interval for the umbilical venous to maternal venous ratio of propofol at delivery was 0.62-0.86. Plasma protein binding studies showed there was less unbound propofol in maternal plasma (1.28-2.29%) compared with umbilical plasma (2.08-3.88%) (P less than 0.01). Neonatal concentrations of propofol were greater than maternal concentrations at 2 h and were in the range 0.05-0.11 micrograms ml-1 at 4 h.

Anesthesia, Obstetrical↗
PubMed1991

A preliminary report on ABO incompatible bone marrow transplant.

Between September 1985 and June 1990, five patients with major and six patients with minor ABO blood group incompatibility between donor and recipient underwent allogeneic bone marrow transplantation (BMT) in the Singapore General Hospital. The period to engraftment, rate of recovery of peripheral blood leukocytes, granulocytes, and platelets and the incidence of graft versus host disease (GVHD) was similar to that observed following ABO blood group compatible marrow transplant. Erythroid development and reticulocytosis were, however, significantly delayed in patients receiving major ABO incompatible marrow transplant.

ABO Blood-Group System↗
PubMed1991

Individualised treatment of seven cases of acquired factor VIII inhibitors.

Seven non-haemophilic patients with acquired Factor VIII inhibitors, admitted to Singapore General Hospital from 1986 to 1990, were studied to analyse their characteristic clinical features and therapeutic outcome. They all had low Factor VIIIC activities, ranged from 0 to 7% and their Factor VIII inhibitors ranged from 1.5 to 128 Bethesda units. All were Chinese aged 30 to 66 years, median 49 years. Six were females, with only one male. Five had associated autoimmune diseases and two had no apparent underlying disorder. One out of seven patients died despite treatment. Therapeutic approach is largely individualised. It may be life-threatening and needs prompt and adequate treatment.

Acute Disease↗
PubMed1990

Induction of specific nonresponsiveness in unprimed human T cells by anti-CD3 antibody and alloantigen.

Fresh peripheral blood mononuclear cells exposed to alloantigen for 3-8 d in the presence of anti-CD3 antibodies showed no response after restimulation with cells from the original donor but remained capable of responding to third-party donors. Antigen-specific nonresponsiveness was induced by both nonmitogenic and mitogenic anti-CD3 antibodies but not by antibodies against CD2, CD4, CD5, CD8, CD18, or CD28. Nonresponsiveness induced by anti-CD3 antibody in mixed leukocyte culture was sustained for at least 34 d from initiation of the culture and 26 d after removal of the antibody. Anti-CD3 antibody also induced antigen-specific nonresponsiveness in cytotoxic T cell generation assays. Anti-CD3 antibody did not induce nonresponsiveness in previously primed cells. Nonresponsiveness induced by anti-CD3 did not appear to be associated with suppressor cell activation. Thus, co-stimulation of the T cell receptor-CD3 complex on unprimed T cells with a fluid phase anti-CD3 antibody and allogenic major histocompatibility complex antigens can induce either clonal anergy or clonal deletion. These results suggest novel approaches for achieving transplantation tolerance.

Antibodies, Monoclonal↗
PubMed1990

Alloantigen-specific T suppressor-inducer and T suppressor-effector cells can be activated despite blocking the IL-2 receptor.

To determine IL-2 requirement for activation of suppressor cells, PBMC were primed in one-way MLR in the presence of 10 micrograms/ml anti-IL-2R beta-chain antibody 2A3 (CD25) or control antibody, then irradiated and added as regulators in a fresh MLR. Cells primed in the presence of antibody 2A3 suppressed the proliferative response to fresh autologous lymphocytes to specific alloantigen but had no effect on the response to cells from third party donors. Priming in the presence of an antibody of irrelevant specificity induced only limited suppressor activity. Activated suppressor cells did not show cytolytic activity specific for the stimulators when tested at the time of the suppressor cell assay. To identify the subset(s) responsible for suppression, cells primed in the presence of antibody 2A3 were separated into CD4+/CD45RA+, CD4+/CD45RA-, and CD8+ subsets, which were irradiated and then tested. The suppressive activity was found predominantly in the CD4+/CD45RA+ subset, whereas CD8+ cells had some activity and CD4+/CD45RA- cells had none. No subset suppressed the response of autologous cells to third-party cells. When primed CD4+/CD45RA+ cells were cocultured with fresh autologous lymphocytes depleted of CD8+ cells, no suppression was observed, indicating that, although the CD4+/CD45RA+ cells can function as inducers of suppressors, they cannot function as suppressor-effectors. Conversely, CD8+ cells activated in MLR in the presence of 2A3 caused suppression, regardless of whether the fresh autologous responder population contained CD8+ cells. CD4+/CD45RA+ and CD8+ subsets isolated after priming in the presence of 2A3 also demonstrated Ag-specific suppression in the generation of cytotoxic T lymphocytes whereas CD4+/CD45RA- cells had no activity. Our data are consistent with the model that suppression of alloreactivity requires the cooperation of two types of cells, a CD4+/CD45RA+ suppressor-inducer and a CD8+ suppressor-effector population. Activated Tsi and fresh Tse or activated Tse alone can suppress lymphocyte proliferation and generation of CTL in response to specific Ag. Activation of Ag-specific T suppressor-inducer and T suppressor-effector cells appears to be relatively IL-2 independent and presumably require one or more other growth factors.

Antibodies, Monoclonal↗
PubMed1990

Comparison of four local extradural anaesthetic solutions for elective caesarean section.

We have examined a combination of two local anaesthetics to see if the resultant solution is superior to the agents individually. This study shows that a mixture of bupivacaine and lignocaine provided an excellent alternative to bupivacaine alone, and was superior to 2% lignocaine with adrenaline for elective Caesarean section. By reducing the dose of bupivacaine used, the combination may reduce the risk of cardiotoxicity.

Adult↗
PubMed1990

Allogeneic bone marrow transplantation for acute non-lymphoblastic leukaemia--the Singapore experience.

Eleven patients with acute non-lymphoblastic leukaemia (ANNL) underwent allogeneic bone marrow transplant (BMT) from the period, September 1985 to June 1989 in the Singapore General Hospital. Five of the six patients (83%) transplanted in the first remission are presently alive; three greater than 2.5 years after the transplant. Two of these three patients are enjoying disease free survival; the other had chronic graft versus host disease but well controlled with treatment. One of the six patients relapsed from his disease at Day 252 post-transplanted and died 8 months later. Four patients who were transplanted in the first untreated relapse and one in second remission have died; three from early post-transplant complications and two from relapse. The results of allogenic BMT in patients with ANNL in first remission in this study appear encouraging and are superior to conventional chemotherapy. Allogeneic BMT should be considered as the treatment of choice in selected groups of individuals with ANNL. (Abbrev.: BMT = Bone marrow transplant; ANNL = Acute non-lymphoblastic leukaemia; GVHD = Graft vs Host Disease; VOD = Veno-occlusive disease)

Adolescent↗
PubMed1990

Bone marrow transplantation for treatment of chronic myelogenous leukaemia (CML)--preliminary experience in Singapore.

Chronic Myelogenous Leukaemia (CML) is a clonogeneic disease with the Philadelphia (Ph') chromosome as a cytogenetic marker. Conventional therapy rarely leads to cure in CML. Treatment of CML by bone marrow transplantation (BMT) is thus a reasonable alternative. This study reports on nine patients in chronic phase CML who were given allogeneic bone marrow transplantation with bone marrow cells from HLA identical siblings. There were 5 males and 4 females. Median age was 25 years (range 15-33 years). Median time from diagnosis to BMT was 8 months (range 25 to 48 months). Conditioning regimens: (i) 4 patients received cyclophosphamide 60 mgm/kg x 2 days and Total Body Irradiation (TBI) 200 rads x 6 doses x 3 days. (ii) 5 patients received busulphan 4 mgm/kg per day x 4 days followed by cyclophosphamide 60 mgm/kg x 2 days. Cyclosporin A (CSA) and methotrexate (MTX) was administered for Graft-Versus-Host-Disease (GVHD) prophylaxis in 8 patients; one patient received CSA and prednisolone. Median time for engraftment and for peripheral blood granulocytes to reach more than 500/ul was 18 days (range 12-30 days). Median time for platelet count to reach more than 20,000/ul was 25.5 days (range 15-30 days). 33% of patients developed acute GVHD of Grade II and above. The acturial survival of the 9 patients is 46%. Eight of 9 patients transplanted had two or more risk factors which adversely affect prognosis in CML. Four patients are alive and in remission at 562, 386, 46 and 46 days post-BMT respectively.

Adolescent↗
PubMed1989

Dispersal of bacteria by an electric air hand dryer.

The potential risk of an electric air hand dryer contributing to airborne infection in a hospital was investigated using a strain of Serratia marcescens and a strain of coagulase-negative, streptomycin-resistant Staphylococcus. Dispersal of marker bacteria by the air dryer was demonstrated within a radius of about 3 feet from the dryer and to the investigator's laboratory coat. When paper towels were used for hand drying, no dispersal of marker bacteria was demonstrated. It is suggested that air hand dryers are unsuitable for use in critical patient care areas as they may contribute to cross infection either via airborne dissemination or via contaminated personnel.

Air Microbiology↗
PubMed1987

Follistatin specifically inhibits pituitary follicle stimulating hormone release in vitro.

Two forms of purified follistatin, a single-chain polypeptide of mol wt 35,000 (35 Kd) protein, and a related molecule of mol wt 32,000 (32 Kd), which differs from the 35 Kd form in glycosylation or carboxyl terminal truncation, specifically inhibit the release of immunoreactive FSH by primary cultures of rat pituitary cells. Both forms of follistatin and inhibin-A give similar dose-response curves, with identical slopes and maximal effects, suggesting that they may all act through the same mechanism on the pituitary cells. The median effective dose (ED50) of each of the follistatins is 6.2-7.3 ng/ml (1.8 x 10(-10) M), which corresponds to approximately 1/3 of the potency of inhibin. The effect of 35 Kd or 32 Kd follistatin is highly specific for suppressing the release of immunoreactive FSH since there is no demonstrable concomitant effect on the secretion of other pituitary hormones. The effect of follistatins, like that of inhibins, is different from that of the hypothalamic hypophysiotropic factors, requiring greater than or equal to 18 h of incubation in a pituitary monolayer culture system to demonstrate. Coincubation of inhibin and follistatin shows an additive effect in the suppression of FSH release. Pituitary cells exposed to follistatin have significantly less depletion of intracellular FSH (0.01) than those treated with inhibin, indicating that follistatin may act primarily on the suppression of FSH release rather than on both release and synthesis of FSH, as is the case with inhibin.

Animals↗