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Biomedical subjects

N H Ruddle

Publications and source records attributed to N H Ruddle.

At least 91 records · Page 5Linked to original sources
PubMed1982

Immunoglobulin heavy chain gene rearrangement and transcription in murine T cell hybrids and T lymphomas.

We have examined the arrangement of immunoglobulin heavy chain constant (CH) and joining (JH) region genes in murine T cell hybrid lines and in T lymphomas. CH genes derived from both parental cell types were present in all hybrids for which polymorphism in sequences flanking CH genes permitted us to distinguish parental CH genes. All T lymphomas and T cell hybrids retained the C alpha gene in germ-line configuration and all but one cell line had germ-line C mu genes. Novel DNA fragments reactive with JH probes were observed in six of nine T cell hybrids, as well as in two T lymphomas, WEHI7.1 and YAC-1, but not in the fusion parent, BW5147. No RNA homologous to C gamma 2b, C alpha, or lambda genes was detected in any of the T cell lines. T cell lines contained poly(A)+ RNA homologous to a C mu cDNA probe. More importantly, in several cell lines the C mu RNAs were associated with membrane-bound polyribosomes. These results suggest that both JH rearrangements and C mu RNA production occur in at least some mature, antigen-specific T cells. They may therefore reflect events in normal T cell development and function related to those involved in the generation of the T receptor for antigen.

Animals↗
PubMed1982

Tubulointerstitial nephritis and immunologic responses to Tamm-Horsfall protein in rabbits challenged with homologous urine or Tamm-Horsfall protein.

Tubulointerstitial nephritis was produced in 19 of 23 New Zealand White rabbits challenged i.v. with adjuvant-free homologous urine for greater than or equal to 16 wk and 11 of 14 challenged with adjuvant-free rabbit Tamm-Horsfall protein for 2 to 24 wk. Lesions were identical in the two groups of rabbits and were characterized by focal mononuclear infiltrates and microscopic scarring localized to distal nephron segments identified as the thick ascending limb of the loop of Henle. Concomitant immunoglobulin deposition was not detected despite antecedent elevations in serum IgG antibody directed against Tamm-Horsfall protein in 17 of 19 and 10 of 11 affected rabbits, respectively. Peripheral lymphocytes from affected rabbits were found to be cytotoxic and underwent blast transformation in the presence of homologous urine or Tamm-Horsfall protein in vitro. These lymphocytes were shown to produce a soluble cytotoxic product upon exposure to Tamm-Horsfall protein. Neither tubulointerstitial nephritis nor this pattern of cellular and humoral immune response to Tamm-Horsfall protein was found in two age-matched control groups: one unchallenged, and the other challenged i.v. with urine that had been selectively depleted of Tamm-Horsfall protein by 95%. It is concluded that the tubulointerstitial nephritis produced in rabbits by injection of urine or Tamm-Horsfall protein is the result of a predominately cellular immune response directed against Tamm-Horsfall protein.

Animals↗
PubMed1981

Development of a protein A enzyme immunoassay for use in screening hybridomas.

A protein A enzyme immunoassay has been developed which is effective in the rapid screening of hybridomas. The detecting reagent is a stable alkaline phosphatase-protein A conjugate, prepared by a simple, inexpensive, single-step procedure. The assay requires small amounts of antigen to coat microtiter wells (less than 25 microgram/well) and can be evaluated visually or with a spectrophotometer. It compares favorably in sensitivity to a protein A-radioimmunoassay and enjoys considerably lower backgrounds than that popular screening procedure.

Animals↗
PubMed1980

Lymphotoxin production by subsets of T cells.

Lymphotoxin is produced by T cells sensitized to antigen upon re-exposure in vitro. It is also elicited by mitogen treatment. Its production has been correlated with delayed-type hypersensitivity and it may be a mediator of that phenomenon. We have examined the Ly phenotype of the subset(s) of T cells that produce lymphotoxin in order to investigate the relationship of lymphotokin killing to allo-killing mediated by Ly2+ T cells. We have found that Ly1 T cells sensitized to ovalbumin secrete more lymphotoxin than Ly2 cells. The ovalbumin-sensitized T cells do not lyse their target in a short term 51Cr-release assay even when "glued" to the target with Con A. Thus, lymphotoxin-producing cells differ phenotypically from the previously defined cytotoxic T cells that bear the Ly2 differentiation marker.

Animals↗
PubMed1979

Delayed hypersensitivity to soluble antigens in mice. II. Analysis in vitro.

Delayed hypersensitivity to a soluble protein has been analyzed in vitro with lymph node cells from mice. Antigen-dependent cytotoxicity against innocent bystander cells, and incorporation of tritiated thymidine have been used to monitor the response to a subcutaneous tail injection of egg albumin (OVA) in complete Freund's adjuvant. Sensitized lymph node cells from mice with positive 24 h ear tests killed A9 cells in the presence of antigen. This antigen-specific, T cell-mediated cytotoxicity was observed within 4 days of sensitization and still apparent at 7 months. Reactivity to OVA, assessed as an increase in DNA synthesis in the presence of antigen, was also T cell dependent and exhibited similar sensitization kinetics and dose requirements. Both microtechniques require as few as 10(5) lymphocytes and are readily adaptable to the study of delayed hypersensitivity to any soluble protein in mice.

Animals↗
PubMed1978

Assignment of the receptor for ecotropic murine leukemia virus to mouse chromosome 5.

The gene for the receptor for ecotropic murine leukemia virus (Rev) has been assigned to mouse chromosome 5. This determination was made possible by an analysis of somatic cell hybrids between mouse and Chinese hamster cells. The parents of these hybrids were A/HeJ or Mus poschiavinus peritoneal exudate cells or BALB/c primary embryo fibroblasts and E36, a Chinese hamster lung fibroblast deficient in hypoxanthine guanine phosphoribosyltransferase. Segregation of mouse chromosomes in these hybrids was analyzed by chromosome banding and isozyme expression. Cells were tested for their ability to absorb and replicate vesicular stomatitis virus (murine leukemia virus [MuLV]) pseudotype particles and ecotropic MuLV as measured by the XC test. The presence of chromosome 5 was essential for receptor expression as determined by three statistical procedures. Segregation of the receptor for ecotropic murine leukemia virus was also followed in two series of subclones. In both, receptor expression was syntenic with phosphoglucomutase-1, an isozyme which has been mapped to mouse chromosome 5.

Animals↗
PubMed1978

Delayed hypersensitivity to soluble antigens in mice. I. Analysis in vivo.

Delayed hypersensitivity to a soluble protein has been analyzed in mice. Ear swelling, 24 h after injection of a test dose of antigen, has been used to monitor the response to a subcutaneous tail injection of egg albumin in complete Freund's adjuvant. Maximal 24 h ear swelling was observed 8 days after sensitization with either 50 or 100 microgram of antigen. These delayed reactions, which were characterized by mononuclear infiltrates, were relatively uncomplicated by Arthus reactions. The latter, antibody-mediated reactions were apparent at later times after immunization. More intense 24 hr reactions were elicited in C57BL/6 than BALB/c mice. Passive transfer of sensitivity has been accomplished with lymph node cells.

Animals↗
PubMed1977

Expression of endogenous murine leukemia viruses during the course of a protracted immunological disorder.

Mice of the low leukemia (BALB/cJ x A/J)F1 hybrid (CAF1) strain express B-and N-tropic infectious murine leukemia virus (MuLV) after the age of 6 mo. Initation of a protracted immunological disorder, the graft-versus-host reaction (GVHR), at 7 wk of age, accelerates the induction of both these mouse-tropic endogenous viruses, and preferentially enhances the replication of B-tropic MuLV. The earlier appearance of B-tropic MuLV in a greater proportion of mice and in higher titer is thought to be casually related to the eventual development of lymphoreticular tumors in the GVHR mice, since previous studies have shown that these same tumors can be reproduced by inoculating syngeneic recipients with serially passaged GVHR extracts containing B-tropic MuLV.

Age Factors↗
PubMed1977

Role of endogenous murine leukemia virus in immunologically triggered lymphoreticular tumors. I. Development and use of oncogenic cellfree preparations serially passaged in vivo.

Cellfree extracts (CFEs) prepared from (BALB/cJ X A/J)F1 (CAF1) and (BALB/cJ X C57BL/6J)F1 (CB6F1) mice in which a graft-versus-host reaction (GVHR) has been induced are known to be oncogenic, but only after a protracted latent period (mean, 16 mo). Serial passage of such CFEs in successive generations of syngeneic mice inoculated at birth led to the development of two separate oncogenic preparations, the CA serioes in CAF, mice and the CB series in CB6F, mice, in which the mean latent period was reduced to 6 and 12 months, respectively. Both oncogenic preparations contained infectious B-tropic murine leukemia virus (MuLV) and particles with the ultrastructural characteristics of MuLV. No other kind of virus particle was seen. When these preparations were injected into infant syngeneic mice, B-tropic MuLV could be detected in the reticular tissues as early as 2 weeks thereafter. The virus persisted in the reticular tissues and was present in the lymphoreticular tumors that subsequently developed. However, if the same preparation was injected into young adult recipients, there may have been transient MuLV replication, but the virus subsequently disappeared from the reticular tissues and no lymphoreticular tumors developed. Previous experiments showed that MuLV was present in CFEs prepared from CAF, animals with the GVHR but absent in those of normal control mice. Since the lymphoreticular tumors arising in mice with the GVHR were the same as those induced by the CA and CB MuLV preparations, it was concluded that tumorigenesis in mice with the GVHR was caused by endogenous B-tropic MuLV activated by the immunologic disturbance.

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