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Biomedical subjects

M J Simons

Publications and source records attributed to M J Simons.

34 records · Page 2Linked to original sources

Immunogenetic aspects of nasopharyngeal carcinoma. V. Confirmation of a Chinese-related HLA profile (A2, Singapore 2) associated with an increased risk in Chinese for nasopharyngeal carcinoma.

Histocompatibility locus A typing of 43 Malaysian Chinese and 51 Hong Kong Chinese patients with nasopharyngeal carcinoma (NPC) confirmed the association between the occurrence of A2-Sin 2 and the increased risk for NPC that was previously demonstrated in Singapore Chinese. The results support the previous interpretation that the histocompatibility locus A genotype of importance in NPC predisposition is the A2-Sin 2 haplotype. The histocompatibility locus A-linked, genetically determined NPC risk is common to Asian Chinese from at least three geographic locations.

Asian People

Impaired general cell-mediated immune functions in vivo and in vitro in patients with nasopharyngeal carcinoma.

General cell-mediated immune (CMI) functions in NPC patients were investigated by the in vivo Mantoux and in vitro lymphocyte response to PHA assays. Thirty-eight (50%) of 76 untreated NPC patients were hyporesponsive in the Mantoux assay compared to 27 (25%) of 110 control patients. Forty-three (65.2%) of 66 untreated NPC patients also showed lymphocyte hyporesponsiveness to PHA compared to 15 (15.5%) of 97 control patients. Combined deficiencies were observed in 35 (42.2%) of 83 NPC patients compared to only 2 (3.3%) of 61 control patients. No difference in the frequency of immunodeficiency was observed between "early" and "late" disease patients. CMI functions of treated "remission" NPC patients were found to be impaired to the same extent as those of untreated NPC patients.

Adult

Immunogenetic aspects of nasopharyngeal carcinoma. IV. Increased risk in Chinese of nasopharyngeal carcinoma associated with a Chinese-related HLA profile (A2, Singapore 2).

The results of this study of 110 Singapore Chinese with nasopharyngeal carcinoma (NPC) and 91 controls confirmed the association between the occurrence of HLA antigen Singapore 2 (Sin2) and NPC in the Chinese population, and indicated that their increased risk for NPC was confined to the joint occurrence of Sin 2 and A2 antigens. These findings suggested that the genotype of importance in susceptibility to NPC is the A2-Sin 2 haplotype.

Asian People

Blood group genetic studies in an urban Chinese population.

The distribution of the blood group systems ABO, Rhesus, MNSs and P was studied in all or some of 1,007 Singapore Chinese, ABO gene frequencies were found to be consistent with previous studies and did not vary significantly between dialects. An individual of phenotype A2B was detected although the population showed no other evidence for the A2 gene. The possible significance of this observation in terms of weak H alleles in the population is discussed. The frequencies of the MNSs genes are consistent with previous studies. Two subjects appeared to lack the NA component of the N antigen. The frequency of the R1 gene of the Rhesus system was lower than has been detected previously and may relate to dialect differences. No examples of the CW antigen were detected. The P blood group distribution appears to be subject to regional variation. It is concluded that classification of Chinese into dialect groups is a useful way of assessing genetic heterogeneity.

ABO Blood-Group System

Immunodeficiency to hepatitis B virus infection and genetic susceptibility to development of hepatocellular carcinoma.

The high frequency of hepatitis B antigen (HBsAg) in hepatocellular carcinoma (HCC) patients has led to the hypothesis that immunoresponsiveness to hepatitis B virus (HBV) may be deficient in some patients, and that the immune response deficiency may have a genetic basis. Radioelectrocomplexing (REC), a radioimmunoassay in gel based on the principle of counterimmunoelectrophoresis (CIE), has been used to identify four HBV immune status subgroups: 1) HBsAg +ve/HBsAb +ve; 2) HBsAg +ve/HBsAb -ve; 3) HBsAb -ve/HBsAb +ve; 4) HBsAg -ve/HBsAb -ve/HBsAb -ve. These subgroups comprise 2, 6, 70, and 22 percent, respectively, among blood donors, and 32, 19, 23, and 26 percent, respectively, among HCC patients. Although the HBV exposure rates in the two groups were similar, the immune complexemic rates and HBs antigenemic rates were significantly higher in HBB patients than in the blood donors. It is proposed that the failure of termination of HBV infection revealed by these high rates reflects an immunodeficiency state characterized by an inability to produce high-avidity HBsAb. The immunodeficiency might have a primary genetic basis, or it might be secondary to the immunodepressive effects of concurrent viral or parasitic infections.

Antigen-Antibody Reactions

Probable identification of an HL-A second-locus antigen associated with a high risk of nasopharyngeal carcinoma.

An HL-A antigen profile comprising an increased frequency of HL-A2 and undetectable second-locus antigen(s) in Chinese patients with nasopharyngeal carcinoma (N.P.C.) has been reported. To investigate whether the deficit of second-locus antigen(s) had a genetic basis, sera from parous women in Singapore were screened for anti HL-A activity corresponding to the second-locus "bland". A second-locus (Singapore-2) was identified which seems to be associated with a high risk of N.P.C.

Antigens, Neoplasm

Hepatitis B antigen, antigen subtypes, and hepatitis B antibody in normal subjects and patients with liver disease.

The relative sensitivities of counterimmunoelectrophoresis (CIE) and haemagglutination assays for the detection of hepatitis B surface antigen (HB(s)Ag) and antibodies (anti-HB(s)) were compared. Twelve scientists from ten countries in Asia, Africa and the Pacific region participated in the study. The participants provided serum samples from 15 953 subjects comprising patients with acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC), as well as blood donors and other normal individuals. For the detection of HB(s)Ag in a reference panel serum, immune adherence haemagglutination (IAHA) was slightly more sensitive than passive haemagglutination inhibition (PHI); CIE was the least sensitive. Mean HB(s)Ag frequencies in patients with acute hepatitis, chronic hepatitis, cirrhosis, and HCC were significantly higher than in healthy controls. Passive haemagglutination (PHA) was more sensitive than CIE for the detection of anti-HB(s). The frequency of anti-HB(s) in patients with HCC was significantly lower than that in the other groups. Mean anti-HB(s) frequencies in patients with acute hepatitis, chronic hepatitis, and cirrhosis were not significantly different from that in normal subjects. Subtyping of HB(s)Ag was performed by PHI. Among asymptomatic carriers the predominant HB(s)Ag subtype in northeast Asia was adr.In India, ayw predominated in carriers, with the demarcation between adr and ayw occurring west of Burma. In West Africa the only subtype detected was ayw, but in East Africa the majority subtype was adw. The r subtype was found only in Asian populations east of India and in Western Pacific populations. In Papua New Guinea all four subtypes were identified. With one possible exception, the subtypes of HB(s)Ag-positive patients with liver disease reflected the predominant type in each geographic location.

Africa

Serum IgE levels in normal subjects and allergy patients among the Chinese in Singapore.

Serum IgE was determined in four groups of Singapore Chinese consisting of 292 normal subjects, 15 patients with atopic dermatitis, 39 with drug allergy and 14 with bronchial asthma. The results were compared with the findings of similar groups in western countries. In the normal subjects the range and means (numerical and geometrical) of serum IgE were four to seven times higher in the Singapore Chinese than reported in the western countries. However, the circulating levels in atopic dermatitis and bronchial asthma patients were comparable. In drug allergy moderate IgE elevation was noted. The serum IgE levels of the normal subjects and patients with atopic dermatitis and bronchial asthma were markedly lower than those found in nearby Papua New Guinea. The significance of these observations is discussed.

Adolescent

Immunogenetic aspects of nasopharyngeal carcinoma (NPC) III. HL-a type as a genetic marker of NPC predisposition to test the hypothesis that Epstein-Barr virus is an etiological factor in NPC.

HL-A typing of 144 NPC patients and 236 controls revealed an increased frequency of 1st locus HL-42 (relative risk = 2.24) and an increased frequency of unidentified antigens at the 2nd locus (relative risk = 2.60) in the NPC patients. HL-A2 and the 2nd locus "blank" appeared to act together (HL-A2 blank haplotype) in determining NPC risk in highest-risk Cantonese, whereas in relatively lower-risk non-Cantonese Chinese (Hokkiens, Teochews) they appeared to act independently. Only the "blank" had an increased frequency in Malay NPC patients. Thus there was an indication that the strength of the HL-A association with NPC reflected the 30-50-fold difference in incidence between highest-risk Cantonese and lowest-risk Indians. In Singapore, HL-A segregation patterns in families of nine Chinese NPC patients confirmed that the "blank" was a genetic phenomenon. A new 2nd locus antigen (Singapore-2) has recently been detected. Singapore-2 occurs more frequently in NPC patients and appears to be associated with a high risk for NPC. Since HL-A2 and Singapore-2 are not the risk factors, it is likely that the HL-A association with NPC reflects the existence of disease-susceptibility (DS) genes in linkage disequilibrium with alleles of the HL-A loci. It is proposed that NPC-DS genes may determine differences in immune responsiveness to environmental agents, and thereby determine differences in NPC incidence. If the known altered immune responsiveness of NPC patients to EBV reflects the function of DS genes linked to the high NPC risk HL-A type, then the hypothesis that Epstein-Barr virus has an etiological role in NPC can be tested by several types of prospective studies.

Carcinoma

Sero-epidemiology of the Epstein-Barr virus: preliminary analysis of an international study - a review.

Samples of Chinese, Indian, African and Caucasian populations, randomly selected in Hong Kong, Singapore, the West Nile District of Uganda, and Nancy, France, were titrated for antibodies to EBV, viral capsid (VCA) and complement-fixing soluble (CF/S) antigens. The age-specific prevalence of infection (as reflected by the proportion of VCA-positive individuals) varied greatly up to the age of 10 years in the four populations studied, the West Nile District of Uganda being outstanding in having an early and massive infection rate. Differences were also observed between ethnic groups in Singapore, where the Chinese appeared to have a delayed infection rate compared to the Indians. Immune response, as measured by the prevalence of CF/S antibodies and by the geometric mean titres (GMT) of VCA and CF/S antibodies, differed significantly between ethnic groups, Ugandan infants (1-3-year age-groups) having a humoral response to VCA and CF/S antigens as high as or higher than that of Burkitt's lymphoma patients, decreasing thereafter to levels lower than those of any other ethnic group observed. Indians in Singapore, known to be at no risk for NPC and BL, exhibited a higher and steadier immune response to VCA in going from young to old age-groups than did the Chinese.

Adolescent

Transfusion of hepatitis B immune complex-containing blood in high HBV prevalence populations.

In several countries where there is a high prevalence of HBV the risk of PTH has been investigated. One study demonstrated that HBV immunity provided protection against infection following transfusion of HBs Ag-postive blood in that a higher proportion of immune recipients failed to develop, or developed only transitory, HBs antigenemia, Forty (61 per cent) of 66 recipients who received HBs Ag positive (IAHA) units developed hepatitis, which was subclinical in 37 (93 per cent) of the 40. Six recipients of HBs Ag-containing units had HBs Ag in the pre-transfusion serum. In four, HBs Ag disappeared in the early post-trasfusion period, and anti-HBs was detected within days, persisting for the duration of the study. The mechanism of this change in HBV immune status is unknown but it may be related to the existence of HBs Ag immune complexemia detectable by radioelectro-complexing in approximately 80 per cent of Hbs Ag-positive blood donors. The phenomenon of apparent "cure" of the HBs antigenemic state warrants further attention.

Antigen-Antibody Complex