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Biomedical subjects

M Segall

Publications and source records attributed to M Segall.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1984

Renal allograft survival in patients with positive B cell crossmatch to their donor.

B cell crossmatches were performed at cold (4 C) and warm (22 C and 37 C) temperatures on 193 renal allograft recipients with negative T cell crossmatches to their donor; 152 of the patients were also tested for autoantibody to autologous B cells. Fifty-six (29%) had a positive B cell crossmatch (21 cold, 35 warm); 14 were autoantibody positive, 23 autoantibody negative, and 19 were not tested for autoantibody. There were no differences in HLA-A, B, C, or DR antigen disparity between the B cell positive (14, 0 DR mismatch; 25, 1 DR mismatch; 9, 0 DR mismatch) and the B cell negative group (40, 0 DR mismatch; 57, 1 DR mismatch; 13, 2 DR mismatch). Similarly, age, diabetic status, and number and type of pretransplant blood transfusions were comparable between B cell positive and negative groups. Although there were no hyperacute rejections, 2-year actuarial graft survival was significantly lower in the B cell positive group, regardless of donor source, graft number, or temperature of reaction. Patients with a positive B cell crossmatch, presumably due to demonstrable autoantibody, may have better graft survival rates than patients with a positive B cell crossmatch and no autoantibody.

Adult↗
PubMed1984

[Measurement of mean retention times of 99mTc-labeled HSA-millimicrospheres in the liver--clinical results in patients with operated breast cancer].

Human serum albumin millimicrospheres labeled with 99mTc-pertechnetate were used for evaluation of their mean retention time in the hepatic RES cells. For this purpose the retention function was derived from the liver time-activity curves by deconvolution analysis. Measurements in 50 patients with operated breast cancer revealed significantly shorter retention times in patients with extrahepatic metastases in comparison with patients without evidence of metastases or recurrences. Discriminant analysis of the retention times combined with other investigated parameters such as relative organ size and extraction fraction of the liver and spleen, age, weight and height of the patient, proved the method to be diagnostically valuable. In the examined group of patients metastases could be demonstrated with a sensitivity of 100% and a specificity of 92%.

Breast Neoplasms↗
PubMed1983

Genetic and molecular analyses of lymphocyte-defined HLA-D region specificities.

Determinants encoded in the HLA-D region have been studied with both cellular (PLT) and molecular (SDS-IEF) methods. When the PLT response against a lymphoblastoid cell line was analyzed by limiting dilution culture and determination of the reactivity of individual cultures against a panel of loss mutants of the initial stimulating LCL, a large fraction of the cultures showed the same pattern, apparently recognizing a determinant associated with DR. In two-dimensional gel analysis of several DR4-positive HLA-D region homozygous cells, the IEF pattern of the DR beta chain correlated with the Dw specificity expressed by the cell. These two pieces of evidence suggest that, although many determinants may contribute to reactivity in mixed leucocyte culture or PLT, an immunodominant determinant associated with the DR beta chain may be the most important single factor in the assignment of Dw specificity.

Epitopes↗
PubMed1983

Planning and politics of resource allocation for primary health care: promotion of meaningful national policy.

Securing resources for primary health care (PHC) involves consideration of the entire health sector: the higher levels of the health service as well as the primary level, and the private and/or social security sub-sectors as well as the government service. Reshaping resource distribution is less a redistribution of existing resources than the allocation of new resources in accordance with PHC priorities. In this the planning of future current costs is a crucial element and requires a budgetary system that identifies expenditures by geographical area and level of care. Resources should be allocated geographically to reduce health care inequalities through the provision of an appropriate mix of different levels of care. Central resource planning and local health care programming (with 'dialogue' between the two) should be the basic planning division of labour, which largely resolves the so-called top-down/bottom-up dichotomy. The private medical sub-sector exerts economic, ideological and political influences on the public health service. Compulsory health insurance schemes can have some similar effects. Success of a PHC policy requires that governments adopt a holistic approach to the health sector. The allocation of health care resources on the bases of need and equity, as opposed to demand, is a political decision. The establishment of a national PHC policy backed up by adequate resources involves a specific politico-technical exercise with four components: research, planning, policy formulation, and government policy decision-making. The resource planning method, based on social epidemiology, is contrasted with conventional health planning methods, based on epidemiology. The articulation of these two approaches is discussed in terms of WHO's Managerial Process for National Health Development.

Costs and Cost Analysis↗
PubMed1983

The effect of mismatching for HLA-DR in recipients of renal allografts sharing one HLA-ABC haplotype with related donors.

The effects of mismatching for DR antigens on renal allograft survival rates have largely been restricted to analyses of cadaver transplant results. Analyses of HLA matching in recipients of transplants from related donors have focused on the number of haplotypes shared between the recipients without regard to DR, or on the total number of HLA antigens mismatched, or on the degree of MLC responsiveness of the recipient to the donor. Most related donor-recipient pairs sharing only one HLA haplotype will be mismatched for DR at the other haplotype, but because there are a limited number of DR alleles, sharing of DR antigens on the mismatched haplotypes occurs relatively frequently. To determine the influence of mismatching for DR on the fate of renal allografts from related donors, we analyzed the results of 172 kidney transplants from related donors who shared one HLA-ABC haplotype with the recipient. There were 156 primary grafts and 16 retransplants; 147 donor-recipient pairs were satisfactory typed for DR antigens. Because genotyping was not usually done, we performed two analyses under two different assumptions. The first assumption was that individuals expressing less than or equal to 1 DR antigen had null antigens, or were homozygous for DR; the alternative assumption was that blanks were true antigens and individuals with blanks were heterozygous. The first assumption is more likely to be correct, and is the assumption used in most analyses of the effect of DR antigen mismatches on the results of cadaveric transplantation. Under the first assumption, of the 147 related donor-recipient pairs in whom DR typing was satisfactory, 33% were mismatched for 0, 64% for 1, and 3% for 2 DR antigens. The one-year absolute graft survival rates in recipients of kidneys from donors with 0 mismatches for DR was 92% (n = 49); in those with one mismatch for DR it was 82% (n = 94); and from those with two mismatches it was 50% (n = 4). The one-year graft survival rate in 25 donor-recipient pairs in which one or both members could not be satisfactorily DR typed was 76%. Differences in graft survival rates between the 0 and 1 and the 1 and 2 DR-mismatched groups were not statistically significant.(ABSTRACT TRUNCATED AT 400 WORDS)

Graft Rejection↗