HLA-DQ RFLP variants of five HLA-DQw2-bearing major histocompatibility complex extended haplotypes.

We have analyzed genomic DNA in a large number of independent examples of five HLA-DQw2-bearing extended haplotypes for their associated subtypes by restriction fragment length polymorphism (RFLP) using DRB, DQA, and DQB probes after Taq I and Pst I digestion and Southern blotting. In addition to three previously described HLA-DQw2 subtypes, DQw2a, DQw2b, and DQw2c, we observed a fourth subtype, HLA-DQw2d, characterized by 5.8 kilobase (kb) DRB/Taq I, 2.

Demonstration of respiratory syncytial virus in an autopsy series.

Respiratory syncytial virus (RSV) antigen was demonstrated in formalin-fixed, paraffin-embedded autopsy tissue using an immunoperoxidase technique. Eighteen autopsy cases were selected on the basis of one of the following criteria: a positive culture for RSV, antemortem or postmortem; positive ELISA test for RSV, antemortem or postmortem; or postmortem histology suggestive of paramyxovirus infection. Controls included three cases from which parainfluenza or influenza virus had been cultured and a case in which the clinical diagnosis of measles was firmly established.

Genetic prediction of nonresponse to hepatitis B vaccine.

In previous studies of the antibody response to hepatitis B vaccine in 598 subjects who received a full course of vaccination, we observed a bimodal response, with about 14 percent producing less than approximately 1000 radioimmunoassay (RIA) units. An analysis of the major histocompatibility complex (MHC) HLA and complement types of 20 of the subjects with the lowest responses indicated a greater-than-expected number of homozygotes for the extended or fixed MHC haplotype [HLA-B8, SC01, DR3]. This finding suggested that the lack of a normal response was a recessive MHC-linked trait.

In vivo transmural potential difference: an early monitor of rejection in small bowel transplantation.

To determine if serial measurements of transmural potential difference (TMPD) can serve as an early monitor of rejection in small bowel transplantation, three groups of rats were studied. The groups are defined as follows: (1) group 1, isolated loop (N = 5): 20 cm of distal jejunum was defunctionalized (Thiry-Vella loop); (2) group 2, isotransplant (N = 5): 20 cm of distal jejunum was isotransplanted between inbred Lewis rats, as a Thiry-Vella loop; the native bowel remained in continuity; (3) group 3, allotransplant (N = 8): allotransplantation as in group 2 but between outbred Sprague-Dawley rats. Using luminal and peritoneal electrodes, TMPD was measured serially every third day.

Failure of tumor necrosis factor to produce hypotensive shock in the absence of endotoxin.

Tumor necrosis factor (TNF) is reported to cause a shock syndrome similar to that produced by endotoxin (LPS). The purpose of this study was to determine the relationship between TNF and LPS in causing shock. Eighty rats received infusions of either TNF, LPS, or TNF plus LPS, as compared with saline solution.

Differential expression of MHC class II antigens in myelomonocytic leukemia cell lines.

Major histocompatibility complex (MHC) class II antigens are discordantly expressed on hematopoietic progenitor cells. Their expression is linked to differential responsiveness of the cells to growth factors and inhibitors. We examined the expression of different MHC class II antigens in a panel of human myelomonocytic cell lines representing different stages of differentiation, by cytofluorographic analysis with monoclonal antibody (MoAb) and Northern blot analysis with specific cDNA probes.

Extended major histocompatibility complex haplotypes in patients with multiple sclerosis.

We derived complete haplotypes of the major histocompatibility complex for 33 patients with MS and their families. The DR2 allele and DR2-bearing extended haplotypes, in proportion, were overrepresented on chromosomes of MS patients compared with parental chromosomes not transmitted to MS offspring. We did not confirm previous reports that particular alleles at the BF locus are overrepresented in MS or that C2 hypocomplementemia is present.

Causes of death after liver transplantation in children treated with cyclosporine and steroids.

Two-hundred-and-twenty-seven children underwent orthotopic liver transplantation between March 1980 and March 1986. Seventy (31 %) patients died during the study period. Four patients who died within 24 hours of the initial liver transplant and 5 patients who died outside of our institution were excluded from the analysis.

Complotypes and extended haplotypes in laboratory medicine.

The region on the short arm of the sixth human chromosome encoding class I and class II histocompatibility antigens involved in immune recognition also encodes a group of molecules unrelated to HLA termed class III which includes C2, C4, and factor B. The four genes encoding the complement proteins occupy about 120 kb of genomic DNA between HLA-B and HLA-DR and are closer to HLA-DR. The four genes are inherited as a single unit, without observed crossover, called a complotype, designated by its BF, C2, C4A, and C4B alleles.

Quantitative variation of C4 variant proteins associated with many MHC haplotypes.

C4 protein variants were analyzed in 64 individuals, of which 51 were either homozygous or heterozygous for an extended major histocompatibility complex (MHC) haplotype (a fixed combination of MHC alleles). The relative amount of each C4 variant was measured by densitometric scanning of stained immunofixed electrophoretic patterns of neuraminidase- and carboxypeptidase-treated samples. The relative concentrations of C4 variants on any haplotype were stable and inherited in families.

Selective sparing of suppressor cells generated in mixed lymphocyte response by an anti-interleukin-2 receptor antibody.

Recent investigations have shown that anti-IL-2 receptor antibodies can prolong cardiac allograft survival in animal models and can be used effectively as primary immunosuppressive therapy in human renal transplantation. While previous studies have established that helper and cytotoxic T cells require IL-2 for proliferation, the role of this lymphokine in suppressor cell development is uncertain. We therefore studied the effects of SA36.

Receptor-like nature of class I HLA: endocytosis via coated pits.

The present investigations show that class I HLA are internalized by macrophage/monocyte type cells. Anti-class I antibody-binding assays show that about 30% of class I Ag present on cell surface are endocytosed within 1 h. Electronmicroscopic investigations reveal that, like other well established receptor molecules, internalization of HLA is mediated by coated pits and coated vesicles.

Serological identification of thymocyte differentiation antigens.

We have examined subfractions of human thymocytes for the expression of novel differentiation antigens. Non-HLA alloantisera procured from multiparous women served as antibody probes. Thymocytes from five individuals were sequentially separated by discontinuous Percoll density gradient centrifugation and a peanut agglutinin (PNA) panning technique.

Familial clustering of scleroderma spectrum disease.

This is the second case report of familial scleroderma (systemic sclerosis) in South Carolina. The family includes two cases of scleroderma meeting American Rheumatism Association criteria, one of systemic sclerosis sine scleroderma, and two other cases of undifferentiated connective tissue disease with features of scleroderma spectrum disorders; there are also two cases of Raynaud's phenomenon (one associated with rheumatoid arthritis), for a total of seven affected relatives. Evidence of scleroderma spectrum disorders was sought in six siblings of the two co-index cases and in 23 of the 35 offspring.

T-cell-defined DR4 subtypes as markers for type 1 diabetes.

In most populations studied, HLA-DR4, a DRB1 (formerly DR beta I) allele, is increased in frequency among patients with insulin-dependent diabetes mellitus (IDDM). Using T-cells, one can distinguish five subtypes of DR4 (Dw4, Dw10, Dw13, Dw14, and Dw15). Two of these (Dw4 and Dw10) are IDDM-associated in the populations studied here.

Murine chromosomal regions correlated with longevity.

In this longevity analysis of 360 BXD recombinant inbred female mice (20 different strains), 2 strains had very significantly shorter survival and 1 strain had very significantly longer survival than the other 17 strains; 4 other strains had less significant lengthening of survival compared to the other 13 strains in a proportional hazards model of survival. Mean survival on the shortest lived strain was 479 days; on the longest lived strain the mean survival was almost double (904 days). Ranges of survival within strain were very large (averaging 642 days), and strain accounted for only 29% of the variation in survival, showing that there are important environmental and/or special developmental effects on longevity even in this colony housed in a single room.

Isolation and sequencing of a cDNA coding for the human DF3 breast carcinoma-associated antigen.

The murine monoclonal antibody (mAb) DF3 reacts with a high molecular weight glycoprotein detectable in human breast carcinomas. DF3 antigen expression correlates with human breast tumor differentiation, and the detection of a cross-reactive species in human milk has suggested that this antigen might be useful as a marker of differentiated mammary epithelium. To further characterize DF3 antigen expression, we have isolated a cDNA clone from a lambda gt11 library by screening with mAb DF3.

The relationship of various aspects of surgical management to outcome in childhood nonmetastatic osteosarcoma: a report from the Childrens Cancer Study Group.

Recently, much attention has been focused on the role of adjuvant chemotherapy in the treatment of osteosarcoma. Surgery, however, remains the primary modality for the ablation of this disease. In this report, we examine the relationship of various aspects of surgical management of osteosarcoma to prognosis for disease-free survival (DFS) in a randomized study of 234 pediatric patients.

1987 Philip Levine award lecture. MHC haplotypes in biology and medicine.

(1) The MHC genes or genes within or near the MHC region are involved in the immune response. The polymorphism of the MHC loci can be used as markers for immune response because the recognition of antigens involves their interaction with the MHC antigens. Specific portions of an antigen bind to the polymorphic region of class II molecules.

Two variants of DRw52, DR3, and DQw2 specificities distinguish two different DR3-bearing extended haplotypes.

HLA-DR beta and DQ beta MHC antigens present on B-lymphoblastoid cell lines homozygous for either [HLA-B8,DR3,SC01] or [HLA-B18,DR3,F1C30] were studied by two-dimensional gel electrophoresis. Comparison of neuraminidase-treated DR proteins from these cells showed that DR3-bearing cells express two DR beta genes. However, one DR beta chain (beta a) is nonpolymorphic, whereas the other beta chain (beta b) is polymorphic.

Monoclonal antibody to human cross-linked fibrin.

Cross-linked Fibrin II was prepared using Kabi grade (L) fibrinogen. Fibrin plasmic digest was separated on Sepharose CL-6B. Fragments Mr 135-300 kDa were used to immunize 6-9 weeks old female BALB-c mice.

Syndromatic paucity of interlobular bile ducts: hepatic histopathology of the early and endstage liver.

Morphologic findings of the liver in syndromatic paucity of intrahepatic bile ducts (SPIHBD) during infancy include paucity of interlobular bile ducts, features of "giant cell hepatitis," dilated lymphatics and veins in the portal tract, perisinusoidal fibrosis, and bile duct epithelial changes with a concentric layering of mesenchymal cells around bile ducts reminiscent of renal dysplasia. The latter change is characteristic of SPIHBD. Although the disease is characterized by paucity of bile ducts, morphometric studies show paucity of interlobular bile ducts in less than half of the patients during infancy.