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Biomedical subjects

M S Pollack

Publications and source records attributed to M S Pollack.

At least 109 records · Page 6Linked to original sources
PubMed1982

The BF locus and HLA: rare alleles coding for functionally active and inactive factor-B products.

The genetic polymorphism of properdin factor B (BF) was studied in different populations. The rarer alleles, BF*F1 and BF*S1, occurred in Caucasians, were less frequent in North American blacks, and were not demonstrated in any of three Oriental populations studied. Two further alleles of BF, termed BF*FM and BF*SM, were found to exist in these populations. The BF*FM allele, which was found only in Caucasians, codes for a functionally inactive factor-B product, whereas the BF*SM allele (found in a single Chinese individual), like other alleles of BF, codes for a functionally active product. HLA haplotype analyses in individuals carrying the rarer alleles of BF revealed not only a strong association between BF*F1 and HLA-B18 and BF*S1 and HLA-Bw50 but an even stronger association between these BF alleles and alleles of the two C4 loci. BF*F1 occurred most frequently on a C4A*3,B*Q0 haplotype, whereas the BF*S1 allele was usually found on a C4A*2,B*1/B*Q0 haplotype. HLA haplotypes carrying the BF*FM and BF*SM alleles all carried the more common C*4A3,B*1 haplotype.

Alleles↗
PubMed1982

Distribution of HLA genotypes in families of patients with acute leukemia. Implications for transplantation.

The HLA genotypes of members of 104 families of patients with acute myelogenous leukemia (AML), 89 families of patients with acute lymphocytic leukemia (ALL), and 40 control families were analyzed. The results indicate that the HLA genotype of both ALL and AML leukemic patients is found more frequently than the expected 25% among their siblings; the increase for AML patients is statistically significant. This suggests that an HLA-linked factor(s) conferring susceptibility to leukemia may also be associated with increased gametic survival. The chance of finding an HLA-matched sibling for bone marrow transplantation is increased.

Acute Disease↗
PubMed1982

Bgb expression in relation to the HLA-B17 antigen splits Bw57 and Bw58 and the cross-reactions of anti-Bgb antibodies.

A substantial number of individuals typed as HLA-B17 do not have Bgb. To determine whether or not this discrepancy reflects genetic or ethnic group differences or the influence of B17 antigen subtypes, a large number of unrelated and related B17 individuals from the Caucasian, Hispanic, Black and Chinese ethnic groups were tested in parallel for Bgb and Bw57- or Bw58- B17 subtype. Higher Bgb expression was found in association with Bw57, but differences in expression of Bgb were also seen in different ethnic groups and in different related individuals carrying the same Bw57 or Bw58 haplotype. Genetic factors other than HLA thus influence the expression of HLa Antigens on red cells. Standard and antiglobulin lymphocytotoxicity tests indicate that all Bgb typing sera contain anti-Bw57 antilymphocyte antibodies and most also contain anti-Bw58 and cross-reacting anti-B12, B15 and/or Bw49 antibodies.

Alleles↗
PubMed1982

Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia.

Hormonal studies and human leukocyte antigen (HLA) genotyping were performed in 5 males and 13 females who were demonstrated to have 21-hydroxylase deficiency. The enzymatic deficiency of steroidogenesis was detected by family studies of 10 females who presented with varying symptoms of androgen excess. The 10 index cases had normal genitalia at birth, but virilized to varying degrees postnatally. The additional 8 affected family members had not sought medical care, but some were found to have signs of virilization on physical examination, while others were normal. Thus both late-onset (symptomatic) and cryptic asymptomatic) 21-hydroxylase deficiency occurred in the same pedigree. The hormonal and genetic linkage studies indicate that the late-onset (symptomatic) form of 21-hydroxylase deficiency, like the cryptic (asymptomatic) and classical forms of 21-hydroxylase deficiency, is transmitted by an autosomal recessive gene which is linked to HLA-B. Furthermore, the classical form of 21-hydroxylase deficiency associated with prenatal virilization is transmitted by an allelic variant for steroid 21-hydroxylase different from that of the nonclassical forms, late-onset (symptomatic) and cryptic (asymptomatic) 21-hydroxylase deficiency. Although these latter 2 disorders have different clinical manifestations, they demonstrate a similar degree of steroid 21-hydroxylase deficiency that is less severe than that observed in classical 21-hydroxylase deficiency. The hormonal and genetic linkage data indicate that cryptic (asymptomatic) and late-onset (symptomatic) 21-hydroxylase deficiency result from the same allelic variant at the steroid 21-hydroxylase locus. A glossary of terms is presented to describe the various allelic forms of 21-hydroxylase deficiency with consistency.

Adolescent↗
PubMed1982

HLA antigens in patients with germ cell cancers of the testis.

The expression of HLA-A, -B, -C, and -DR antigens has been analyzed in 145 unrelated Caucasian patients with germ cell tumors of the testis. Eighteen of these patients had pure seminoma, while the remaining patients had nonseminomatous tumors with embryonal carcinoma, teratocarcinoma, choriocarcinoma, and/or yolk sac components, with or without seminoma. Increases were noted in the frequencies of Aw33, B5, DR5, and DRw6 among the patients with pure seminoma, A3 and B7 among the patients with embryonal carcinoma with or without seminoma, and Aw32 among the patients with yolk sac tumor components. A decrease in the frequency of HLA-DR3 was noted in all patients subgroups, although none of these differences were statistically significant after correction for the number of antigens tested. HLA typing results for three affected brothers of patients indicate that, in each family, the affected sibling pair share at least one HLA haplotype. The etiological and prognostic significance of this finding and of the increases in a few HLA antigen frequencies in particular patient groups and the overall decreases in DR3 remain to be determined.

Diseases in Twins↗
PubMed1981

Transplantation for acute leukaemia with HLA-A and B nonidentical parental marrow cells fractionated with soybean agglutinin and sheep red blood cells.

A new procedure for enrichment of marrow precursors and removal of T lymphocytes from large volumes of human bone marrow, involving initial differential agglutination of T lymphocytes and mature marrow elements with soybean agglutinin, followed by rosetting with sheep red blood cells, was used to fractionate marrow cells from an HLA-A, B, DR non-identical, MLC non-reactive, paternal donor for transplantation into an infant with acute leukaemia. This transplant became completely engrafted and resulted in full recovery of normal, donor-derived haematopoietic function without graft-versus-host disease, sustained for 11 weeks after transplantation, at which time the patient's leukaemia recurred. Subsequently, the patient received chemotherapy and achieved a remission with regeneration of normal marrow cells of donor origin. The patient's course demonstrated the potential of lectin-separated marrow grafts to restore durable haematopoiesis, without graft versus host disease, in a lethally irradiated allogeneic host.

Agglutinins↗
PubMed1981

Human leukocyte anitgen in torticollis and other idiopathic dystonic syndromes.

Two groups totaling 67 patients with idiopathic focal, segmental, and generalized dystonia, including torticollis, were compared with normal controls to determine whether there was a difference in the frequency of A, B, and C locus human leukocyte (HLA) antigens. The results indicated no statistically significant deviations in HLA antigen frequencies between the patients and the normal controls. Thirteen of the patients with idiopathic torsion dystonia were compared with normal controls for DR locus antigens. A trend of increased DR3 antigens observed in the patients may be significant. HLA genotyping of parents and children in nine families was also studied to determine if an HLA-linked factor could be related to the dystonic syndrome in the children. The results were indeterminate, suggesting that further family studies are required to resolve this issue.

Adult↗
PubMed1981

Technical and theoretical considerations in the HLA typing of amniotic fluid cells for prenatal diagnosis and paternity testing.

HLA typing of amniotic fluid cells has been used for the prenatal diagnosis of the HLA linked diseases congenital adrenal hyperplasia (21-OH-deficiency (21-OH-def) type) and complement C4 deficiency and it has also been used for the prenatal determination of paternity. There are, however, technical difficulties in this test associated with the weak expression of some B locus antigens on amniotic fluid cells, and theoretical difficulties related to associations between particular HLA antigens and the 21-OH-def allele. Since certain HLA-B locus antigens are found in significantly increased frequencies among patients with 21-OH-def, there is a relatively high incidence of HLA-B homozygosity among the patients and over 40 per cent of the parents of these patients share one or more HLA-B locus antigens. Results of some prenatal HLA typing tests may thus be difficult to interpret, and supplementary tests should be used whenever possible. HLA typing of amniotic cells is, however, the only available procedure for prenatal diagnosis of C4 deficiency and it is the best available procedure for prenatal determination of paternity. A modification of our original procedure allows HLA typing to be performed with increased numbers of HLA typing sera, and sera with optimum reactivity for amniotic fluid cells have now been selected for the definition of most of the more commonly expressed HLA antigens. Although amniotic fluid cells do not express DR Antigens, amniotic fluid cells can be typed for the HLA-linked marker glyoxalase I (GLO) and this may be the informative for prenatal diagnosis in some cases.

Adrenal Hyperplasia, Congenital↗
PubMed1981

The biochemical basis for genotyping 21-hydroxylase deficiency.

We describe three different forms of 21-hydroxylase deficiency-classical congenital adrenal hyperplasia (CAH), late-onset 21-hydroxylase deficiency, and cryptic 21-hydroxylase deficiency-and we present hormonal standards by which to assign the appropriate 21-hydroxylase deficiency genotype for these disorders. The late-onset and cryptic forms of 21-hydroxylase deficiency are biochemically indistinguishable, although patients with the late-onset disorder present with marked clinical symptoms (e.g. virilization) whereas patients with cryptic 21-hydroxylase deficiency are clinically asymptomatic. Our latest studies suggest that late-onset 21-hydroxylase deficiency, like the classical and cryptic 21-hydroxylase deficiencies, is also genetically linked to HLA, the major histocompatibility complex of man. Our biochemical findings provide evidence that a spectrum of 21-hydroxylase deficiencies exist in the population.

Adolescent↗
PubMed1981

HLA genotypes and HLA-linked genetic markers in Italian patients with classical 21-hydroxylase deficiency.

HLA genotype and HLA-linked marker data for 40 unrelated patients from central Italy and 2 unrelated patients from Sardinia with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) were analyzed. The results confirm that the HLA-linked 21-OH-def gene is associated with several different HLA determinants and complete HLA haplotypes, although the only determinant with significantly increased frequency was the complement C2 allele C2B. The HLA antigens B8 and DR3 were found in significantly decreased frequencies. The haplotype A3, Cw6, Bw47, BfF, DR7, which is exceptionally rare in the general population but which has been found in many other 21-OH-def patients from diverse geographical origins, was also found in one of the Italian patients. This and other HLA haplotype associations found among the Italian patients may represent mutations that have occurred on HLA haplotypes with genetic linkage disequilibrium or, alternatively, may represent mutations that have not yet had time to become randomly associated with different HLA complex determinants. The marked negative associations with B8 and DR3 could, however, result from an interaction between the gene products of the HLA complex and the 21-OH-def phenotype.

Adrenal Hyperplasia, Congenital↗
PubMed1981

Differential inhibition of the MLR by iron: association with HLA phenotype.

The effect of iron on the MLR was examined by pretreating peripheral blood mononuclear cells from 77 unrelated Caucasians with five concentrations of Ferric-citrate (10.0 mM, 1.0 mM, 0.1 mM, 0.01 mM and 0.005 mM). After incubation with the metal, the cells were washed and cultured in a one-way MLR with a pool of stimulator cells. Cell viability remained unchanged (greater than 90 percent) during the 6-day culture period. Citrate per se had no effect on either the responder or the stimulator population. Iron treatment influenced the MLR in the following ways: (1) a variable degree of inhibition was observed which related to the dose of Ferric-citrate used and to HLA phenotype, (2) the responder but not the stimulator cells were affected, (3) no statistically significant differences were seen between female and male donor cells and (4) the mean percent response of cells from HLA-A2 donors were significantly (0.005 less than P less than 0.01) less susceptible to iron exposure than those from non-HLA-A2 individuals. The present results indicate that iron can interact with lymphoid cells and influence some immunological functions in vitro. The possibility is discussed that similar interactions take place in vivo which could contribute to the prognosis of certain diseases associated with particular HLA phenotypes.

Adult↗
PubMed1981

Marrow transplantation for juvenile osteopetrosis.

Two children with the juvenile form of osteopetrosis were treated with marrow transplants from their HLA identical siblings. Following transplantation each child exhibited extensive bone reabsorption with a marked augmentation of osteoclastic function attributable to donor osteoclasts, including remodeling of bone with expansion of intramedullary hematopoiesis and correction of associated abnormalities of thymic factor and natural killer cells. Osteopetrosis ultimately recurred in one patient in whom engraftment of donor hematopoietic elements was not achieved. Our studies indicate that marrow transplantation will correct osteopetrosis but that permanent reconstitution necessitates sustained engraftment of marrow precursors of cells with osteoclastic activity.

Bone Marrow Transplantation↗
PubMed1981

HLA-A, B, C and DR alloantigen expression on forty-six cultured human tumor cell lines.

Forty-six cultured cell lines of diverse human tumor origins, including 25 melanoma cell lines, were HLA allotyped with the use of a modified eosin complement-dependent cytotoxicity test in combination with absorption and two-color fluorescence techniques. In 10 cases (1 renal cell carcinoma line and 9 melanoma cell lines), the cell line donors had been HLA typed a few years before the cell line-typing project had started and in 13 cases (1 renal cell carcinoma line and 12 melanoma cell lines), the cell line donors were currently available for comparative typing of lymphocytes. HLA-typing results suggested that most cell lines expressed genetically appropriate HLA antigens, although 1 cell line had more than two HLA antigens for one HLA locus and 2 cell lines lacked expression of one or more HLA antigens in comparison with donor typing. One hepatoma cell line, 1 of 2 of the bladder carcinoma cell lines tested, and 17 of the 25 melanoma cell lines expressed DR alloantigens in addition to their HLA-A, B, and C locus antigens. For 9 of the melanoma cell lines, comparisons with donor DR alloantigens could be made, and all these cell lines had exactly the same DR allospecificities as those found on donor B-lymphocytes. HLA typing of cell lines can be used as an adjunct to polymorphic isoenzyme marker tests to verify their patient source and lack of contamination by another cell line, and HLA typing should be used to determine the antigen composition of cells used in the preparation of reagents for immunotherapy or in studies of tumor-specific immunity.

Cell Line↗
PubMed1981

HLA-linked genetic markers in Chinese and other Oriental populations.

The polymorphic variants of the HLA-linked genetic markers Bf, C2, C4 and GLO-I were studied in three mongoloid populations. Analysis of linkage dis-equilibrium between these markers and HLA-A, B, C and DR antigens was carried out on test results from 140 unrelated Chinese individuals. The phenotypes BfS and GLO-2 were found at significantly higher frequencies than in Caucasians. BfS was associated with B12 in Japanese but not in Chinese. A single individual with the rare Bf variant S1 was found. No C2 deficient individuals were observed. The C2C (common) allele occurred at a gene frequency of 0.949 and the more basic allele C2B at 0.039. The acidic variant, C2A, was observed at a frequency of 0.011 and appeared to be associated with BfF. Eighty-nine per cent of the Chinese were phenotypically C4FS. In contrast to Bf and C2, each of which is coded for by codominant alleles at a single genetic locus, C4 is coded for by two genes, C4F (Rodgers) and C4S (Chido). The C4F locus allele, C4F1 (extra fast), was strongly associated with HLA-B17, as has been found in other populations, but a new association of the C4S locus deficiency allele, C4so (Ch-), with B17 was also observed. All HLA-B17;C4so haplotypes were BfS position. As has been previously found in Caucasian populations, individuals of the C4F phenotype (i.e. genotypically FsoFso) were all found to be Chido negative. The frequencies of the various HLA-linked genetic markers, however, as much as the frequencies and associations of the HLA antigens themselves, distinguish these populations from other ethnic groups.

Asian People↗
PubMed1981

HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) has been established to be an HLA-linked, recessive monogenetic disease. However, two nonclassical forms of 21-OH-def have also been described: "cryptic" 21-OH-def, which has been shown to be HLA-linked, and "late onset" 21-OH-def, for which the status of linkage to HLA has been less certain. We now describe studies of eight additional unrelated probands with symptomatic, "late onset" 21-OH-def, and conclude that this form is also HLA-linked. Both "late onset" and "cryptic" 21-OH-def are highly associated with the same HLA antigens and markers (HLA-B14, HLA-DR1, and Bf type S) in individuals from different ethnic and geographical backgrounds. Since both "late onset" and "cryptic" 21-OH-def appear to occur in individuals with one classical 21-OH-def (21-OHCAH) allele who in addition have another 21-OH-def allele, as well as in individuals who appear to be homozygous for variant 21-PH-def alleles, and since both late onset and cryptic 21-OH-def appear to occur in the same families, our data suggest that these syndromes may represent different clinical expressions of similar or identical nonclassical 21-OH-def alleles.

Adolescent↗