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J F McCormick

Publications and source records attributed to J F McCormick.

15 recordsLinked to original sources

Identification of I-E alpha genes in H-2 recombinant mouse strains by F1 complementation.

Nine recombinant H-2 mouse strains with crossovers in the I region between I-E-negative haplotypes f,q and I-E-positive haplotypes p,k were examined for I-E expression by microcytotoxicity dye exclusion assay. These recombinants were found to be negative for I-E expression. There are two possible genotypes in these recombinant mouse strains that could result in lack of I-E expression. Recombinants with crossovers between the E alpha gene and the S region would have both nonexpressed I-E alpha and beta genes (E beta fE alpha f, E beta qE alpha q) and recombinants with crossovers between the E beta and E alpha genes would have a nonexpressed E beta gene (E beta f or E alpha q) and a functional E alpha gene (E alpha k or E alpha p). To distinguish between these possible genotypes these recombinants were crossed to B10.A(4R), which carries a functional E alpha k gene but is I-E-negative due to a nonexpressed E alpha b gene. F1 mice were examined for transcomplementing I-E molecules by immunoprecipitation of 3H-leucine-radiolabeled detergent lysates of spleen cells with a monoclonal I-E antibody (14-4-4). Detection of a transcomplementing I-E molecule was confirmed by immunoprecipitation with a monoclonal antibody (H9-14.8) specific for the I-Ek beta polypeptide chain derived from B10.A(4R) and by tryptic peptide map comparisons. Five recombinant mouse strains were able to complement with B10.A(4R) in F1 mice to generate a transcomplementing I-E molecule, and thus have an expressed I-E alpha gene (E alpha k or E alpha p). Four recombinants did not complement with B10.A(4R) in the F1 expression of I-E molecules, and thus have nonexpressed I-E alpha genes (E alpha f or E alpha q).

Animals↗

Serological confirmation in Ia mutant B6.C-H-2bm12 of gene conversion.

Recently it has been suggested that a short segment of the DNA sequence of the Ia beta gene in the mutant B6.C-H-2bm12 (bm12) is derived from the Eb beta gene by a gene-conversion-like mechanism, and that the same segment is also seen in the Ek beta gene. To obtain serological evidence for this idea, we produced an antibody against the "new" determinant on the I-Abm12 molecule by immunizing A.BY mice with bm12 cells. After absorption with B6 lymphocytes to remove antibodies against background antigens, the antisera lysed bm12 cells. Typical Ia peaks were obtained by immunoprecipitation. The absorbed antiserum reacted with B10.A (Ek beta), B10.A(5R) (Eb beta) and B10.S(9R) (Es beta), but not B10. The unabsorbed antiserum is specific for Ia when tested on A background mice. The antiserum lysed spleen cells of Ik strains (A/Sn, A.AL, A.TBR1, and A.TFR1) but not Ak strain, A.TBR13 (KsAkEbSbDb), confirming the presence of antibodies against the I-Ek molecule. This anti-serum also lysed the cells from (A.BY X A.TFR5)F1, which expresses the transcomplementing Eb beta Ek alpha molecule and from the (A.SW X A.TFR5)F1 which expresses the transcomplementing Es beta Ek alpha molecule. These data are consistent with DNA sequence analyses, and show the existence of a determinant (Ia.51) generated in the bm12 mutant by a gene-conversion-like event that is also present in the I-Ek, I-Eb, and I-Es beta polypeptide chains.

Animals↗

Experimental chronic vaginal candidosis in rats.

In the past, the rat model of experimental vaginal candidosis has been used to study the efficacy of antifungal agents in eradicating acute vaginitis. In the present study, chronic vaginal candidosis was induced to study the natural history of the infection. Results indicate that chronic infection is readily achieved and is strictly dependent on oophorectomy and hormonal maintenance of pseudoestrous. Histologic studies confirm that rats so infected and with long term vaginal carriage of Candida albicans have true chronic infection with extensive mycelial formation and superficial mucosal invasion.

Animals↗

Renal hemangiopericytoma: surgical, radiological and pathological implications.

The first case of renal hemangiopericytoma presenting radiologically as a hypovascular mass is described. Preoperative diagnostic evaluation included ultrasonography, retrograde pyeloureterography, computerized tomography and angiography. Electron microscopy is helpful to distinguish this lesion from histologically similar juxtaglomerular cell tumors. Although renal hemangiopericytoma may appear benign on pathological examination it should be treated as a low grade malignancy and followed carefully.

Hemangiopericytoma↗

The formation of endothelial webs and channels in plasma clot culture.

Rings of rat aorta cultured in plasma clots gave rise to microvascular networks. Scanning electron microscopy revealed that, in most cultures, the newly formed microvessels communicated with an endothelial-lined chamber which had developed around the aorta. The endothelial cells lining the wall of this chamber were elongated and frequently overlapped each other forming unicellular or multicellular bridges. The endothelium also produced solid bands and webs which spanned wide regions of the periaortic chamber and of the aortic lumen. Solid endothelial ropelike structures overran the openings of the newly formed vascular channels and connected the outer wall of the chamber with the aortic ring. Webs were composed of branching cords of spiraling endothelial cells with or without collagenized cores. Webs and bands formed as a result of the extensive surface remodeling of the fibrin clot by developing endothelial channels. These structures are reminiscent of the intimal bands and webs which develop in human blood vessels as a late sequela of the organization of thromboemboli.

Animals↗

Anatomy of the chick chorioallantoic membrane relevant to its use as a substrate in bioassay systems.

Scanning electron microscopy was used in this investigation to characterize and contrast the chorionic surface of 11 day chick chorioallantoic membranes (CAM) prepared by either the classical dropping technique or the Zwilling technique. The structure of the chorionic blood sinus and its relationship to the chorionic ectoderm were also examined. The Zwilling CAM has been proposed as the substrate in an assay being developed by investigators in this laboratory, an assay which is intended as an alternative to the Draize Rabbit Eye Irritancy Test. The purpose of this study was to define the substrate. The results show considerable uniformity of the Zwilling CAM surface in comparison to the dropped CAM. Broad areas of exposed basement membrane were an unexpected finding on the surface of the dropped CAM. It appears that this basement membrane is made up of more than just the thin discontinuous basal lamina seen with the transmission electron microscope. The findings of this study are pertinent to chick embryo physiology as well as to toxicologic assays and tumor cell assays which utilize the CAM.

Allantois↗

Hybrid (combinatorial) Ia specificities: gene complementations to generate Ia.22.

Ia specificity 22 is expressed on a hybrid I-E molecule formed by the association of a beta chain (Ae) coded for by the I-A subregion and an alpha chain (E alpha) encoded by the I-E subregion. Ia.22 can be generated by the complementation of Ab, Ak, As, Ar, with Ed, Ek, Ep, Er, Ew3, Eu, Ev but Eb, Ef, Eq, and Es. With the exception of H-2p which does not complement with As to generate Ia.22, all Ia. 7-positive (I-E) haplotypes can provide the permissive E alpha allele. It is postulated that Ia.22 is a combinatorial Ia determinant generated by the association of the alpha and beta chains. These determinants are probably involved in the immune recognition of antigens under dual Ir-gene control.

Animals↗

Serological and biochemical analysis of Ia molecules in the I-A mutant B6.C-H-2.

Strain B6.C-H-2bm12 has a mutation in the I-A subregion of the mouse H-2 gene complex, which causes skin graft rejection, mixed lymphocyte reaction (MLR), and alterations in the expression of Ia antigens. The mutation affects the expression of Ia.3, 8, 9, 15, and 20 on normal spleen cells. When the spleen cells were stimulated with lipopolysaccharide (LPS), the expression of all Ia specificities were found except Ia.8. Ia molecules when internally labeled with 3H-leucine can be precipitated with antisera directed against Ia.3, 9, 15, and 20, but not Ia.8. When F1s are made between the mutant bm12 and unrelated haplotypes, Ia.3, 9, 15 and 20 can be detected by microcytotoxic assay on normal spleen cells, but not Ia.8. These studies suggest: (1) The mutation affects either the amount of Ia molecules expressed on normal spleen cell surfaces or the molecule is anchored improperly in the cell surface such that it is not accessible for cytotoxicity and radioiodination. (2) Specificity Ia.8, which may be a combinatorial determinant, is absent in the mutant because of a structural alteration in one of the chains, probably the beta chain. (3) The mutation does not involve the Ae chain. The significance of this finding in relation to I region-mediated allorecognition and antigen presentation is discussed.

Animals↗

Radionuclide imaging and computed tomography in renal oncocytoma.

Renal oncocytoma is an apparently benign neoplasm that is being reported with increasing frequency. It is important to differentiate it from renal-cell carcinoma prior to surgery. Angiographic, CT, and ultrasound studies may suggest the diagnosis but are not pathognomonic. In 4 cases, 99mTc-glucoheptonate imaging of the renal tubules was performed; one patient was also scanned in 131I-orthoidohippurate. There was no evidence of radionuclide uptake by the tumor. Reasons for the lack of success in differentiating renal oncocytoma from renal-cell carcinoma are discussed.

Adenocarcinoma↗

Detection of hybrid (combinatorial) Ia antigens using parent anti-F1 sera.

Ia specificities 22 and 23 were initially identified by using conventional alloantisera and were mapped to the I-E subregion of k and d haplotypes on the basis of their reactivity with selected recombinants. Recently we found that Ia 22 and 23 are hybrid determinants on the basis of their expression on selected F1 cells, but absence from both parental cells. Initial attempts to detect hybrid Ia antigens by immunizing parents with F1 cells were unsuccessful. By utilizing lipopolysaccharide (LPS)-stimulated F1 spleen lymphoblasts as immunogens, 1 of the parents as recipient and the other parent cells for absorption of antisera, specific anti-Ia.22 and 23 antibodies were produced. The specificity of these parent anti-F1 sera was confirmed by cytotoxic and immunoprecipitation analyses.

Absorption↗

Serological and biochemical identification of hybrid Ia antigens.

Ia specificities 22 and 23 were found to be determinants on hybrid Ia molecules by serological and biochemical studies. Lipopolysaccharide-stimulated splenic lymphocytes from (B10 X B10.D2)F1 expressed Ia.22 although both the parents were negative. Similarly [D2.GD X B10.A(5R)]F1 cells expressed Ia.23, whereas D2.GD and B10.A(5R) lacked it. Ia.22 can be generated by gene complementation of Ak-Ek, Ab-Ed, Ab-Ek, As-Ed, and As-Ek, whereas Ia.23 can be generated by Ad-Ed, Ad-Ek, and Ad-Ep. Other possible complementing combinations are under study. The role of Ia.22 and 23 in mixed lymphocyte reactions and immune responses are discussed.

Electrophoresis, Polyacrylamide Gel↗

Gene complementations to generate Ia antigens (Ia.23) on hybrid molecules.

Ia specificity 23 is a "combinatorial" antigen generated on a hybrid I region molecule, formed by the noncovalent binding of a 26,000- to 28,000-dalton beta polypeptide chain (Ae) coded by a gene in the I-A subregion with a 32,000- to 35,000-dalton alpha chain (E alpha) coded by a gene in the I-E subregion of the mouse H-2 gene complex. For expression of Ia.23, the Ae chain must be derived from the H-2d haplotype (I-Ad), while the E alpha can be provided by I-Ed, I-Ek, I-Ep, I-Er, I-Ev, and I-Ew3, but not I-Eb, I-Ef, I-Eq, I-Es, and I-Eu. With the exception of H-2u haplotype, all Ia.7 (I-E)-positive haplotypes can provide the permissive E alpha chain for generating Ia.23 by trans-complementation. In the H-2d haplotype, Ia.23 is generated by cis-complementation of Ad with Ed. Lymphocytes of F1 animals expressed two I-E subregion coded hybrid Ia specificities; one formed by cis-complementation and another by trans-complementation. It is postulated that such hybrid determinants are involved in the recognition and generation of immune response to antigens such as GL-Phe and cytochrome C where dual Ir gene control has been demonstrated. It is also suggested that there are two types of Ia specificities: (1) allotypic Ia specificities expressed on the alpha or beta chains (these could aid in the binding between the alpha and beta chains such as Ia.7); and (2) hybrid Ia specificities which are unique interaction determinants formed by the specific association of the alpha and beta chains (e.g., Ia.22,23). These interaction gene products may be involved in antigen recognition and presentation.

Animals↗

Lack of gene complementation prevents expression of I-Ek in recombinant A.TFR5.

The I-E molecule is produced by complementation of genes in I-A (Ae) and I-E (E alpha). Ia specificities 22 and 23 are generated by the hybrid molecule, whereas Ia.7 is an allotypic determinant presumably on the alpha-chain of the I-E molecule. Recombinant A.TFR5 (AfEk) lacks detectable I-E molecule since Af and Ek cannot complement. In a cross between A.TFR5 and B10.A(4R) (AkEb), Aek and E alpha k can successfully complement to express the I-Ek molecule on the cell surface of the heterozygote. Haplotypes H-2b and H-2s can also provide the permissive Abe and Ase molecules for complementation with Ek alpha of A.TFR5.

Absorption↗

Unilateral tubo-ovarin actinomycosis in the presence of an intrauterine device.

A case of unilateral tubo-ovarian abscess due to Actinomyces in the presence of an intrauterine device is presented. The gross and microscopic features are described. As the diagnosis of this potentially serious infection is usually made by the histologic demonstration of sparsely distributed sulfur granules, the pathologist should approach every case of IUD-associated pelvic inflammation with a high index of suspicion.

Abscess↗