Binding of rabbit hemorrhagic disease virus to antigens of the ABH histo-blood group family.
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The ability of rabbit hemorrhagic disease virus to agglutinate human erythrocytes and to attach to rabbit epithelial cells of the upper respiratory and digestive tracts was shown to depend on the presence of ABH blood group antigens. Indeed, agglutination was inhibited by saliva from secretor individuals but not from nonsecretors, the latter being devoid of H antigen. In addition, erythrocytes of the rare Bombay phenotype, which completely lack ABH antigens, were not agglutinated. Native viral particles from extracts of infected rabbit liver as well as virus-like particles from the recombinant virus capsid protein specifically bound to synthetic A and H type 2 blood group oligosaccharides. Both types of particles could attach to adult rabbit epithelial cells of the upper respiratory and digestive tracts. This binding paralleled that of anti-H type 2 blood group reagents and was inhibited by the H type 2-specific lectin UEA-I and polyacrylamide-conjugated H type 2 trisaccharide. Young rabbit tissues were almost devoid of A and H type 2 antigens, and only very weak binding of virus particles could be obtained on these tissues. (+info)
Bovine alpha1,3-galactosyltransferase catalytic domain structure and its relationship with ABO histo-blood group and glycosphingolipid glycosyltransferases.
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alpha1,3-galactosyltransferase (alpha3GalT, EC 2.4.1.151) is a Golgi-resident, type II transmembrane protein that transfers galactose from UDP-alpha-galactose to the terminal N:-acetyllactosamine unit of glycoconjugate glycans, producing the Galalpha1,3Galbeta1,4GlcNAc oligosaccharide structure present in most mammalian glycoproteins. Unlike most other mammals, humans and Old World primates do not possess alpha3GalT activity, which is relevant for the hyperacute rejection observed in pig-to-human xenotransplantation. The crystal structure of the catalytic domain of substrate-free bovine alpha3GalT, solved and refined to 2.3 A resolution, has a globular shape with an alpha/beta fold containing a narrow cleft on one face, and shares a UDP-binding domain (UBD) with the recently solved inverting glycosyltransferases. The substrate-bound complex, solved and refined to 2.5 A, allows the description of residues interacting directly with UDP-galactose. These structural data suggest that the strictly conserved residue E317 is likely to be the catalytic nucleophile involved in galactose transfer with retention of anomeric configuration as accomplished by this enzyme. Moreover, the alpha3GalT structure helps to identify amino acid residues that determine the specificities of the highly homologous ABO histo-blood group and glycosphingolipid glycosyltransferases. (+info)
Comparison of the three rat GDP-L-fucose:beta-D-galactoside 2-alpha-L-fucosyltransferases FTA, FTB and FTC.
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The complete coding sequences of three rat alpha1,2fucosyltransferase genes were obtained. Sequence analysis revealed that these genes, called FTA, FTB and FTC, were homologous to human FUT1, FUT2 and Sec1, respectively. A distance analysis between all alpha1,2fucosyltransferase sequences available showed that the two domains of the catalytic region evolved differently with little divergence between the FUT2 and Sec1 N-terminal domains, quite distant from that of FUT1. At variance, FUT1 and FUT2 C-terminal domains were less distant while a high evolutionary rate was noted for Sec1 C-terminal domain. Whereas FTA and FTB encode typical glycosyltransferases, FTC lacks the homologous start codon and encodes a protein devoid of intracellular and transmembrane domains. It is located on rat chromosome 1q34. Transfection experiments revealed that unlike FTA and FTB, FTC does not generate enzyme activity. Analysis by flow cytometry showed that H type 2 epitopes were synthesized in Chinese hamster ovary cells transfected by both FTA and FTB cDNA, but only FTB transfectants possessed H type 3 determinants. In REG rat carcinoma cells, both FTA and FTB allowed synthesis of H type 2 and H type 3 at the cell surface. Western blots showed that, in both cell types, FTA was able to synthesize H type 2 epitopes on a larger set of glycoproteins than FTB. Analysis of the kinetic parameters obtained using small oligosaccharides revealed only a slight preference of FTA for type 2 over other types of acceptor substrates, whereas FTB was barely able to fucosylate this substrate. (+info)
Human genetic factors related to susceptibility to mild malaria in Gabon.
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Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-alpha and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sickle-cell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-alpha promoter mutations (at positions -238: 0.17 and -308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position -238 of the gene coding for the promoter region of TNF-alpha was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum. (+info)
Pretreatment determination of isohaemagglutinin titter values in patients with malignant lymphomas and metastatic solid tumors.
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Isohaemagglutinin synthesis starts 2-4 months after birth, growing progressively and reaching adult values at the age of 5-10 years. Isohaemagglutinin concentration decreases with age. Isohaemagglutinins are mostly immunoglobulins belonging to the class IgM, but also IgA and IgG. Agglutination titter shows correlation with the total concentration of those three immunoglobulin isotypes. For the time being there are few data on the isohaemagglutinin titter level in various diseases. Purpose of this work is to determine whether there are any isohaemagglutinin titter alterations in patients with neoplasia. Isohaemagglutinin titter was investigated in 177 patients treated at the Institute of Oncology and Radiology and 340 blood donors. Out of 177 patients, 31 had Hodgkin's lymphoma (HL), 89 had non-Hodgkin Lymphoma (NHL) and 57 had metastatic solid tumors (MST). Statistical evaluation included Kruskal-Wallis and Mann-Whitney tests. In all groups of patients isohaemagglutinin titters were considerably lower as compared with the healthy population (p < 1 x 10e-5). There was a significant difference in titter values (p = 0.003) between O blood group patients with NHL where anti-A1 titter was significantly lower (Med = 8; range: 1-256) compared with anti-A1 titter in patients with O blood group suffering from MST (Med = 16; range: 2-64). Anti-B titter in the same groups of patients also showed lower values (p = 0.042); in NHL anti-B titter values was Med = 4, range: 1-32 vs Med = 8, range: 1-64 in MST. In the group of patients with HL, A blood group was far more frequent (17/31) compared with the group with MST (22/57) (p = 0.02). Pretherapy determination of isohaemagglutinin titter in patients with malignant diseases shows that it is significantly lower than the titter in healthy population. Abnormally low isohaemagglutinin titter value irrespective of the type and site of the malignant tumor, points to insufficiency of the IgM-related humoral immune response, to malignancy as a systemic disease, and places isohaemagglutinins among biological markers. (+info)
Oesophageal atresia in the South West of England.
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A retrospective anatomical and family study was made of 345 patients with oesophageal atresia who were born in the South West of England between 1942 and 1973. There were 186 males and 159 females. Twenty-one cases were stillborn. Eighty-five percent of the patients had a combination of oesophageal atresia with a tracheo-oesophageal fistula to the distal oesophageal segment, and 9 percent had atresia without a fistula. Fifty-five per cent of the patients had other congenital malformations and these tended to be multiple rather than single. Thirty-six per cent of singletons had unequivocal fetal growth retardation, and there is some evidence that nearly all cases have poor fetal growth. There appeared to be a maternal age effect, with an excess of mothers under 20 and over 35, and there was an unexplained excess of fathers employed in the Armed Forces. Ten per cent of the cases were illegitimate. There were 21 twins which is nearly three times the expected number; there were two pairs of twins concordant for oesophageal atresia, one being monozygotic and the other dizygotic. In one case there were two sibs with oesophageal atresia. Five out of 365 sibs had anencephaly. The blood group distributions of the patients and their mothers did not significantly differ from the expected distribution. Oesophageal atresia is aetiologically heterogenous. In this series there were at least five, and probably 10 cases of trisomy 18 and four cases of trisomy 21. Five mothers had overt diabetes, and there is some suggestion from other work that maternal diabetes or its treatment may be aetiologically important. Oesophageal atresia was part of a possibly recessively inherited malformation syndrome in two cases. A sibship with a case of rectal atresia, a case of Hirschprung's disease and a case of oesophageal atresia may represent the action of another recessive gene. It seems likely that oesophageal atresia is a rather non-specific consequence of several teratological processes. (+info)
Prevention of maternal-fetal blood group incompatibility with traditional Chinese herbal medicine.
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OBJECTIVE: To evaluate the effect of traditional Chinese herbal medicine on the prevention of hemolytic disease caused by maternal-fetal blood group incompatibility. METHODS: A total of 126 Chinese patients with maternal-fetal blood group incompatibility were studied, including 105 cases of ABO type and 21 cases of Rh type incompatibility. The traditional Chinese herbal medicine was used for preventative treatment in 79 cases, and 47 cases served as controls. The prescription consisted of Herba leonuri 500 g, white peony root 180 g, Banksia rose 12 g, root of Chinese angelica 150 g and Rhizomal ligustica 150 g. RESULTS: Preventative treatment with traditional Chinese herbal medicine significantly reduced the perinatal mortality rate in cases of Rh type incompatibility, from 50.0% in the control group to 7.7% in the treatment group (P < 0.05). There was no death in the cases of ABO incompatibility. The traditional Chinese herbal medicine also decreased the degree of hemolysis. The percentage of severe cases in the control group was 29.8%, while it was 15.2% in the treatment group (P = 0.05). The duration of treatment was closely related to the outcomes. In patients who used traditional Chinese herbal medicine for more than 10 weeks, the incidence of severe hemolysis was 8.2%, compared with 38.9% in those treated for less than 10 weeks (P < 0.05). The change of serum immune antibody (A and/or B) titers during the treatment was a very important predictive factor for the outcome of the pregnancy. CONCLUSION: Traditional Chinese herbal medicine is effective not only for ABO type but also for Rh type maternal-fetal blood group incompatibility, with no side effects. (+info)
Haptoglobin-ABO interaction: a possible explanation for the excess of Hp 1 among offspring of ABO incompatible matings.
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The Hp1 frequency among ABO phenotypes varies in the Hutterite population as follows: O less than A less than B less than AB. Within group O, the Hp1 frequency is significantly lower than the Hp1 frequency among the other groups combined. The Hp1 frequencies among ABO genotypes, known by means of family pedigrees, vary as follows: OO less than AO less than BO less than AB less than AA less than BB. This holds for both main subjects of this isolate, although they have been reproductively isolated since World War I. The higher Hp1 frequency among type A, B, and AB individuals explains the observation of the higher Hp1 frequencies found among H-leut offspring who are incompatible with their mothers (mainly AO offspring of OO mothers) compared to offspring from the same matings who are compatible with their mothers. (+info)