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M Segall

Publications and source records attributed to M Segall.

At least 37 records · Page 2Linked to original sources
PubMed1991

Serology, restriction fragment length polymorphism, and sequence analysis of a unique HLA class II antigen, DR5x6.

We analyzed a new class II HLA haplotype, which we have designated DR5x6, by serology, restriction fragment length polymorphism (RFLP), and sequence analysis. As the name DR5x6 implies, the antigen is serologically closely related to both DR5 and DRw6. RFLP analysis of this haplotype suggests a close similarity with DRw11 haplotypes. The DNA sequences encoded by the second exon of its DRB1, DRB3, and DQB1 genes were also determined. Comparison of these sequences with those of alleles at these loci in other haplotypes suggests that this haplotype could have evolved from a DRw11 ancestor haplotype (DRw11-DRw52b (Dw25)-DQw7) by means of: (a) a gene conversion at the DRB1 locus involving DRw8 (Dw8.3) as the sequence donor, plus a point mutation or a gene conversion involving DR4-Dw4; and (b) a recombination event by which this haplotype would have acquired the DRw5a (Dw24) allele at the DRB3 locus.

Base Sequence↗
PubMed1991

Hypoxic pulmonary hypertension: changes in platelet size and number.

Circulating platelets have been implicated in the hypoxic pulmonary pressor response. This study was undertaken to assess the effects of acute hypoxia-induced pulmonary hypertension on platelet volume and number across the pulmonary circulation in anesthetized newborn lambs. Seven animals were instrumented for measurement of pulmonary vascular resistance. All measurements were made during normoxia and after 5 and 30 minutes of hypoxia (10 to 12% oxygen breathing). Hypoxia caused a doubling of the pulmonary vascular resistance. During hypoxic vasoconstriction, platelet volume decreased rapidly while traversing the lung but was not affected on return to the lung after traversing the systemic circulation. Platelet numbers were unchanged on leaving the lung but were decreased on entering the lung during hypoxia. Our data are consistent with the release of platelet contents in the lung during hypoxic pulmonary hypertension.

Animals↗
PubMed1988

Genetic relationships between type I and type II diabetes mellitus.

We propose that at least certain subsets of Type I and Type II diabetes share factor(s) responsible for genetic susceptibility. The data presented here to support this contention include: 1. A significantly increased cumulative risk (CR40) to age 40 for Type I diabetes in sibs of probands in families with a Type II diabetic parent (Type II diabetic parent: CR40-24.7 +/- 10.7%; normal parent: CR40 = 7.5 +/- 2.0%, x2 = 12.8, p less than 0.0005). 2. The relative risk (RR) for HLA DR4 in Type I diabetic probands with a Type II diabetic parent is higher than in probands with normal parents (RR = 2.4). 3. The haptoglobin genotype 2-2 is increased in Type I diabetics with Type II parents and the sharing of both HLA and haptoglobin haplotypes in affected sib pairs is distorted with an excess sharing of both haplotypes.

Age Factors↗
PubMed1988

HLA and genetics of IDDM. Holism vs. reductionism?

Analysis of HLA-associated susceptibility to insulin-dependent diabetes mellitus (IDDM) has largely focused on identifying the susceptibility gene. Adherents of a countertrend have long suggested the importance of analysis of HLA haplotypes (combinations of alleles on 1 chromosome) rather than individual genes. Accumulating data suggest that the relationship between IDDM susceptibility and HLA is much more complex than a single susceptibility gene. Consideration of this question should include the possibilities that 1) more than one HLA gene is involved in determining susceptibility or resistance; 2) different alleles of the same gene may be associated with different pathogenetic mechanisms; and 3) different susceptibility-associated haplotypes, even if they share an allele at an IDDM-relevant locus, may behave differently in IDDM. A better understanding of the genetics, and perhaps the pathogenesis, of IDDM may be obtained by following up the clues offered by analysis of the association of HLA haplotypes (rather than individual alleles) with one another, with clinical features of IDDM, and with possible non-HLA-linked susceptibility factors.

Alleles↗
PubMed1987

Comparison of DR beta 1 alleles from diabetic and normal individuals.

Insulin-dependent diabetes (IDD) is positively associated with HLA-D proteins. A critical question is whether or not sequence differences within the HLA-D coding region are the same or different in diabetics and normal individuals of the same haplotype. We have isolated both DR beta 1 alleles from a Dw4/LD MN2 cDNA library and compared them to DR beta 1 genes isolated from normal individuals of the same Dw phenotype. We found no nucleotide differences in the coding region between the normal and diabetic alleles of DR beta 1 suggesting to us that DNA differences other than the DR beta 1 coding region may account for the observed association of HLA-D and diabetes.

Alleles↗
PubMed1986

DNA restriction fragment length polymorphisms characteristic for Dw subtypes of DR2.

DNA restriction fragment length polymorphisms (RFLP) can be easily demonstrated in DNA of cells expressing different DR specificities when class II cDNA probes are used for hybridization. Previous studies of DR4+ homozygous typing cells (HTCs) carrying different Dw subtypes, however, detected no RFLP correlating with subtypes. In contrast, we report here Southern blotting studies of DR2+ HTCs carrying different subtypes which showed RFLP patterns characteristic for each subtype, using both DR beta and DQ beta probes and several restriction enzymes. The RFLP between subtypes of DR2 was, however, appreciably lower than that found between DR specificities.

DNA↗
PubMed1986

DR2+ haplotypes in insulin-dependent diabetes: analysis of DNA restriction fragment length polymorphisms.

Insulin-dependent diabetes (IDD) is strongly associated with certain HLA class II (Ia) antigens. The frequency of DR2 is significantly reduced in IDD; among DR2+ patients, the frequency of the subtype specificity Dw2 defined with homozygous typing cells (HTCs) is significantly reduced compared to DR2+ controls, and the specificity LD-MN2, which we have defined using primed lymphocyte typing reagents, is significantly increased. We have studied DNA restriction fragment length polymorphisms (RFLP) of DR2-LD-MN2+ individuals and homozygous typing cells carrying specificities antigenically related to LD-MN2. Using a number of different restriction enzymes, a characteristic pattern of fragments could be defined for DR2-LD-MN2 using both DQ beta and DR beta cDNA probes. This pattern was shared with some but not all of the antigenically related HTCs, and was distinct from that of DR2-Dw2. The RFLP pattern of DR2-LD-MN2 obtained with the DQ beta probe is identical, except for one band, to that of DR1-Dw1, suggesting that at least some part of the DQ region is identical in these two haplotypes. These results indicate that analysis of RFLP patterns can be used to help identify the genetic regions and, eventually, genes most important in the association of HLA and IDD.

Alleles↗
PubMed1986

Dw subtypes of DR4 in rheumatoid arthritis: evidence for a preferential association with Dw4.

We have determined the frequency of the DR4-associated Dw subtypes, defined by homozygous typing cells, in a group of rheumatoid arthritis (RA) patients on second-line drug therapy. The frequency of DR4 in these patients was 86%. Among Caucasians, the frequency of Dw4 in the DR4-positive patients was significantly increased (68%) as compared to DR4-positive normal individuals (46%; p less than 0.025). Dw4, as compared to the other DR4 subtypes tested, may also be associated with more severe disease as judged by indices of functional impairment and joint damage. In a small subgroup of non-Caucasian (black and Native American) patients, the Dw13 (DB3) subtype of DR4 was often seen, suggesting that RA may have different Dw associations in different ethnic groups.

Arthritis, Rheumatoid↗
PubMed1985

Southern analysis of DNA polymorphism among Dw subtypes of DR4.

DNA from individuals of four Dw subtypes of DR4 (Dw4, Dw10, Dw14, Dw15) were studied using Southern blotting to determine if subtype-specific DR beta or DQ beta restriction fragment polymorphism could be found. Although very little polymorphism was found among ten DR4 homozygous individuals (4 Dw4, 2 Dw10, 3 Dw14, 1 Dw15) using a Dr beta or a DQ beta probe, restriction fragment polymorphism was easily detected between different DR types (DR1-DRw8). The possible evolutionary significance of the lack of Dw-associated polymorphism relative to DR-associated polymorphism is discussed.

DNA Restriction Enzymes↗
PubMed1985

Insulin-dependent diabetes--associated HLA-D region encoded determinants.

We have studied the relative frequency of Dw specificities (defined with homozygous typing cells or primed LD (lymphocyte defined) typing reagents) associated with DR4 and DR2 in the normal and insulin-dependent diabetic population. Our findings demonstrate that there is a highly significantly increased frequency of Dw4 in DR4 positive diabetics as compared with normals and a significantly decreased frequency of Dw2 and Dw12 in the few DR2 positive insulin-dependent diabetics that we have found. In addition, we have used PLT reagents to define a new LD specificity, LD-MN2, that is associated with DR2 and is found significantly more frequently in DR2+ IDD patients than in DR2+ normals. These results suggest that determinants of import in the association between HLA-D and IDD may be more closely related to Dw than to DR.

Adolescent↗