PubMed Health⌕ Search

Biomedical subjects

M M Chan

Publications and source records attributed to M M Chan.

At least 37 records · Page 2Linked to original sources
PubMed1993

T cell response in murine Leishmania mexicana amazonensis infection: production of interferon-gamma by CD8+ cells.

The immune response to Leishmania major has been the subject of many investigations. However, Leishmania includes many species with different clinical manifestations. In this report, we studied the T cell response to L. mexicana amazonensis, a New World species, in a murine model. We found that, similar to L. major, an Old World species, resistant C57BL/6 mice produced a high level of IFN-gamma and a low level of IL-4. Conversely, susceptible BALB/c mice produced a much lower level of IFN-gamma and higher level of IL-4. Although IFN-gamma is one of the important lymphokines that mediate macrophage activation and thus the destruction of the intracellular parasites, which lymphocyte subsets are producing the IFN-gamma is still a controversy. Much evidence including the isolation of protective, IFN-gamma-producing, CD4+ cell lines have confirmed the participation of CD4+ Th1 cells unequivocally. However, both CD4+ and CD8+ cells produced IFN-gamma. Recently, an increasing body of evidence has appeared suggesting that CD8+ cells also play a role in the resolution of murine L. major infection. We found that in the L. m. amazonensis model, when CD8+ lymphocytes from resistant C57BL/6 mice were eliminated by anti-CD8 antibody and complement-mediated lysis, the IFN-gamma production was reduced by 77%. This indicated that CD8+ cells produced a significant amount of the IFN-gamma. However, our results also indicate that IFN-gamma production by CD8+ cells was dependent on CD4+ cells.

Animals↗
PubMed1993

Analysis of the repertoire of human B-lymphocytes specific for type A and type B blood group terminal trisaccharide epitopes.

Naturally occurring serum antibodies specific for the A and B blood group isoantigens are of great importance in medicine. By using A-type terminal trisaccharide (ATS) or B-type terminal trisaccharide (BTS) coupled to albumin as coating antigens, an enzyme-linked immunosorbent assay capable of detecting all ATS/BTS-binding antibodies was performed. The combination of this enzyme-linked immunosorbent assay with limiting-dilution methodology, using a polyclonal B-lymphocyte activator, permitted a monoclonal analysis of the human antibody repertoire that is specific for ATS and BTS in persons of different blood types. Most (78%) positive supernatants from type O cultures were monospecific for either ATS or BTS, and these were present at roughly equivalent frequencies. Nine supernatants with reactivity toward both ATS and BTS were tested by red cell adsorption; six had properties expected for true dually reactive monoclonal antibodies: adsorption with either A1 or B red cells eliminated both anti-ATS and anti-BTS activity. This finding accords with a monoclonal origin for anti-A,B. The analysis of cultures of peripheral blood lymphocytes from type A and B donors unexpectedly showed significant numbers of clones with apparent autospecificity. However, none of the anti-ATS-positive supernatants from type A cultures or anti-BTS-positive supernatants from type B cultures were adsorbable with A1 or B red cells, respectively. Consideration of only true (adsorbable) positives indicates that the type A and B anti-trisaccharide repertoires differ significantly from the type O repertoire, probably as a result of the action of normal self-tolerance mechanisms.

ABO Blood-Group System↗
PubMed1993

Structure-function analysis of antimicrotubule dinitroanilines against promastigotes of the parasitic protozoan Leishmania mexicana.

Although leishmaniasis is a major tropical disease, the currently available drugs are toxic and inadequate. We show that the antimicrotubule herbicide trifluralin has antileishmania activity. The present study aimed at deducing the relationship between the structure of the molecule and its antiprotozoan activity. Nine dinitroanilines, all of which were analogs of trifluralin, were compared. We found that pendimethalin was 2.5-fold more potent than trifluralin, and the higher efficacy may be correlated with molecular structural features that increase the accessibility to one nitro group. This association was further supported by molecular modeling. Moreover, trifluralin samples from two sources differed in their activities by more than threefold, and gas column chromatography showed that impurities were present in the more potent sample.

Aniline Compounds↗
PubMed1992

Confirmation of the human cathepsin B gene (CTSB) assignment to chromosome 8.

Human cathepsin B gene (CTSB) has been mapped to two locations: 8p22 and 13q14. Here we confirm the chromosome 8 assignment by three independent methods: (1) analysis of human-hamster somatic cell hybrid DNA by polymerase chain reaction; (2) comparison of hybridization signals to cathepsin B in interphase nuclei of normal fibroblasts and fibroblasts with a chromosome 8 deletion; and (3) fluorescence in situ hybridization to metaphase spreads using cathepsin B cosmid clones. Our results indicate that human CTSB is located at 8p22-p23.1.

Base Sequence↗
PubMed1991

Correlation of cyclosporine and metabolite binding to cyclophilin and a 50 kDa binding protein with in vitro immunosuppression: a preliminary report.

Seven purified cyclosporine (CsA) metabolites were analyzed for binding to cyclophilin and to a 50 kDa protein purified from a JURKAT cell line. In addition, the potency of the seven metabolites, relative to CsA, was obtained using a primary mixed lymphocyte culture (MLC) suppression assay. CsA, M1, 17, and 21 were found to be immunosuppressive in the concentration range used (0-500 ng/mL). These results were then compared to protein binding. CsA and metabolite 17 (M17) bound to both proteins. Conversely, M1, 13, 21, and 26 bound only to cyclophilin, while M8 and M18 bound only to the 50 kDa protein.

Amino Acid Isomerases↗
PubMed1991

The neonatal immune response to washed and irradiated red cells: lack of evidence of lymphocyte activation.

A total of 21 neonatal infants (11 males and 10 females) were evaluated for lymphocyte subpopulation changes and cellular activation following the receipt of washed and gamma-irradiated red cells. The mean donor exposure was 2 +/- 1.5 donors, and the mean white cell concentration of each 10-mL-per-kg transfusion was 2 x 10(7) cells. A total of 2800 rad (28 Gy) was delivered to each red cell unit prior to washing. The lymphocyte subsets CD3+, CD4+, CD8+, CD19+, CD3+/CD25+, CD3+/HLA-DR, CD4+/CD45RA, CD4+/CDw29, and CD4+/ICHL-1 were analyzed, as were plasma gamma-interferon and neopterin levels, before and after blood transfusion. Posttransfusion samples were obtained from 3 to 12 days after the last blood transfusion. There were no posttransfusion changes in the percentage of lymphocyte subsets analyzed. Furthermore, overlay-histogram analysis of pretransfusion and posttransfusion CD45RA-, CDw29-, and UCHL-1-positive helper T cells failed to reveal a shift in mean channel fluorescence intensity, which is indicative of a lack of cellular activation. Gamma-interferon levels remained unchanged after transfusion (range, 90 +/- 5.9 to 95.5 +/- 5.3 pg/mL), as did neopterin levels (range, 3.7 +/- 1.5 to 4.6 +/- 1.5 ng/mL). This study could not find any evidence, by either cellular or humoral markers, of the activation of neonatal lymphocytes by transfusion. It is hypothesized that this failure to observe lymphocyte activation is due to the low number of donor white cells present in washed, irradiated red cells and/or to a lack of recipient recognition of transfused, allogeneic, donor white cells.

Blood Transfusion↗
PubMed1991

Effects of consumption of caloric vs noncaloric sweet drinks on indices of hunger and food consumption in normal adults.

This study examined the effects of aspartame, saccharin, and sucrose on hunger and food intake. Twenty normal adults consumed a standard breakfast followed 3 h later by 200 mL of either water or a sweetened drink. One hour later, subjects' ad libitum consumption of a standardized lunch was measured. Subjects recorded self-assessments of hunger-related indices every half hour on visual analogue scales (VAS). ANOVA with repeated measures showed a significant effect of drink type on VAS scores 15 and 45 min after drinks were consumed but not for other times or for lunch consumption. Hunger-related ratings after drink consumption were generally highest for water, lower for noncaloric sweeteners (NCSs), and lowest for sugar. Pairwise comparisons of means showed that only the ratings for sugar and water were significantly different. The results show that, under the conditions of this study, NCSs do not increase hunger or food intake.

Adult↗
PubMed1991

Immune dysfunction in children after corrective surgery for congenital heart disease.

OBJECTIVE: To study the effect of open- and closed-heart surgery on the immune status of infants and children. DESIGN: Prospective study. Data collected before anesthesia and surgery and 2 and 24 hrs after surgery. SETTING: Operating room and pediatric ICU in a children's hospital. PATIENTS: Children undergoing surgery for correction of congenital heart disease (age 3 months to 12 yrs). A total of 31 patients were studied (open-heart surgery, n = 25; closed-heart surgery, n = 6). MEASUREMENTS AND MAIN RESULTS: Increased neutrophil counts and lymphopenia were observed after both open- and closed-heart surgery. Serum levels of the complement components C3 and C4 were depressed after open-heart surgery, but not after closed procedures. The percentage of T3+ and T4+ lymphocytes, proliferative responses of the lymphocytes and serum immunoglobulin (Ig)G and IgM were decreased from preoperative levels after open-heart surgery. The percentage of T8+ lymphocytes and serum IgA levels did not change. Intraoperative variables and postoperative severity of illness (Pediatric Risk of Mortality score) did not correlate with immune suppression. CONCLUSIONS: The immune system is affected after pediatric cardiac surgery, particularly after open-heart surgery.

Cardiac Surgical Procedures↗
PubMed1991

A preliminary study to evaluate an in vitro assay for determining patient whole blood immunosuppressive cyclosporine A and metabolite activity: comparison with cytosolic binding assays using cyclophilin or a 50-kilodalton binding protein, and the Abbott TDx cyclosporine A parent, and parent and metabolites assays.

Thirty-five allograft recipients undergoing cyclosporine A (CsA) therapy were randomly selected to evaluate a "novel" in vitro assay that determines CsA and metabolite immunosuppressive activity in whole blood. The assay uses a third party mixed lymphocyte culture (MLC) system to which patient whole blood extracts containing CsA and metabolites are added. The ability of the extracted CsA and metabolites to inhibit proliferation in this system is proportional to the immune suppressive activity in whole blood. Comparison of the MLC suppression assay against Abbott TDx parent, TDx parent and metabolites, and radioreceptor assays utilizing cyclophilin or a 50-kDa binding protein isolated from JURKAT cytosol gave the following correlation coefficients: r = 0.612, r = 0.672, r = 0.362, and r = 0.775, respectively.

Amino Acid Isomerases↗
PubMed1991

Effect of the anti-microtubule drug oryzalin on growth and differentiation of the parasitic protozoan Leishmania mexicana.

The parasitic protozoan Leishmania mexicana differentiates from a non-motile intracellular amastigote in the mammalian macrophage phagolysosome into a motile, extracellular promastigote in the insect vector gut. This developmental program has been accomplished in vitro, thus providing a useful model for studying changes in the cytoskeleton during cell differentiation. The role of microtubules in leishmania differentiation was demonstrated by using the dinitroaniline herbicide oryzalin, which inhibited both leishmania proliferation and differentiation; 25 microM oryzalin reduced promastigote division by over 95%. Interestingly, at a sublethal dose (5 microM), promastigotes became round and multiflagellated but remained motile. At 50 microM oryzalin, the number of intracellular amastigotes decreased by 50%. However, leishmania differentiation seemed to be the most drug-sensitive stage: there was a 60% reduction in amastigote-to-promastigote differentiation at 0.5 microM oryzalin. The specific action of oryzalin on leishmania microtubules was verified by its inhibition of in vitro polymerization of leishmania microtubules, but not control mammalian microtubules (from rat brain). These findings indicate that microtubules play a major role in leishmania proliferation, maintenance of cell shape, and cytodifferentiation.

Animals↗
PubMed1991

Gene mapping of human cathepsins and cystatins.

Chromosomal locations of human cathepsin B, stefin A and kininogen have been determined. Using techniques of somatic cell hybrids and polymerase chain reaction, cathepsin B has been mapped to 8p22, stefin A to 3cen-q21, and kininogen to 3q26-qter. Comparing this data with currently available mapping loci, it can be concluded that many members of cathepsins are dispersed in different chromosomes, whereas members of the cystatin family are restricted to only two human chromosomes, 3 and 20.

Cathepsin B↗
PubMed1990

Inhibition of leishmanias but not host macrophages by the antitubulin herbicide trifluralin.

The dinitroaniline herbicide trifluralin (alpha, alpha, alpha-trifluoro-2,6-dinitro-N, N-dipropyl-p-toluidine), at micromolar concentrations, selectively inhibited both proliferation and differentiation of the parasitic protozoan Leishmania mexicana amazonensis. In vitro, radioactive trifluralin showed specific binding to leishmania tubulin but not to mammalian tubulin. Because herbicides such as trifluralin are economical and are considered safe for man and domesticated animals, they may serve as useful sources of potential antiparasitic agents.

Animals↗
PubMed1990

Lack of association between slow acetylator status and spontaneous lupus erythematosus.

The Chinese in Southeast Asia are recognized as a population group that has a relatively high prevalence of rapid "acetylators" and a relatively high incidence of systemic lupus erythematosus. This study was designed to evaluate the possibility that there were environmental lupus erythematosus provocative substances eliminated by acetylation that resulted in a preponderance of slow acetylators among patients with the disease. We compared acetylator status in 36 Chinese women with mild, stable, and confirmed lupus erythematosus and 36 healthy control subjects matched for age, sex, and ethnic origin. Acetylator status was determined by use of HPLC to assay 5-acetylamino-6-formylamino-3-methyluracil/methylxanthine (AFMU/MX) and AFMU/(AFMU + MX) ratios in urine 1 to 4 hours after drinking a strong cup of coffee (caffeine). By use of parametric and nonparametric methods of analysis, the frequency distribution of AFMU/MX and AFMU/(AFMU + MX) ratios in both the patients and control subjects were determined to be very similar. Thus there was no association between slow acetylator status and lupus erythematosus in the study subjects.

Acetylation↗
PubMed1990

Beta 2-microglobulin and neopterin: predictive markers for human immunodeficiency virus type 1 infection in children?

The value of beta 2-microglobulin and neopterin concentrations in serum for early diagnosis of infants born to human immunodeficiency virus type 1 (HIV-1)-infected mothers was assessed. Concentrations of both markers were measured in serum samples from pediatric patients (Centers for Disease Control classifications P0, P1, and P2), as well as in age-matched normal subjects. Both beta 2-microglobulin and neopterin were significantly increased in HIV-1-infected symptomatic subjects (P2) compared to controls. Seventy-five percent of asymptomatic patients (P1) also had increased values. On the other hand, a significant overlap in concentrations of both markers in serum was found between controls and P0 patients. Thirty-eight percent of the P0 patients had values comparable to those of the P2 group. Persistently high concentrations of both markers in P0 patients may be indicative of HIV-1 infection.

Biomarkers↗