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Biomedical subjects

J A Sogn

Publications and source records attributed to J A Sogn.

At least 19 recordsLinked to original sources
PubMed1990

Cancer immunology: highlights of the NCI Extramural Immunology Program.

The long-term goal of research supported by the Immunology Program is to better understand immune mechanisms and their regulation in order to develop more effective strategies to strengthen the immune response against cancer. While there has been much progress in the field of immunology in recent years, many major questions remain unanswered. The role of MHC antigens in regulating the immune response to tumors is still unclear, as is the nature of putative tumor-associated antigens which are the targets of this response. The efficacy of various immune cell subsets in tumor cell killing is differentially affected by changes in tumor cell surface MHC antigen expression. Furthermore, although we now know much more about the cellular interactions in the immune response, little is actually known about the particular cell subsets which participate in an immune response is regressing versus progressing tumors. Interleukins have been shown to stimulate a variety of immunes response, and some of these immune modulators are now being tested in clinical trials, in various stages, to determine their antitumor effects. However, systemic administration of large quantities of interleukins can result in very different effects than those created by the local release of effector molecules from specific T-cell populations. Effector T cells can deliver lymphokines to precise target structures, whereas systemically administered lymphokines would affect preferentially those cells expressing the largest numbers of high affinity receptors for the lymphokines. The specificity of lymphokines as mediators of immunologic response rests largely or exclusively in the local release of such materials by T cells upon activation by antigen: MHC complexes on a stimulating cell. Because lymphokines show specificity only for nonantigen-specific, non-MHC-restricted receptor molecules on target cells, the effect of lymphokine injections is likely to be determined solely by the expression of these receptors. Thus, lymphokines function well as effector molecules in a number of specific immune reactions, but it remains to be determined whether they will be useful in regulating immune responses in specific disease situations. It may be critical to recruit specific immune cells to the area of tumor growth where they, in turn, can release lymphokines to activate appropriate antitumor effector cells. Adoptively transferred T cells of the helper phenotype can induce an effective antitumor immune response in recipient mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Viral gene inhibition of class I major histocompatibility antigen expression: not a general mechanism governing the tumorigenicity of adenovirus type 2-, adenovirus type 12-, and simian virus 40-transformed Syrian hamster cells.

The association between the level of class I major histocompatibility (MHC) antigen expression and the tumorigenic phenotype was determined for cells from a series of 15 lines of adenovirus type 2 (Ad2)-, Ad12-, and simian virus 40 (SV40)-transformed hamster cells and 16 lines of cells established from hamster tumors induced by SV40 mutants. These cells range from nontumorigenic to highly tumorigenic in both syngeneic and allogeneic adult hamsters. The Ad2-transformed cells--cells that were nontumorigenic in syngeneic adult hamsters--expressed either high levels or low levels of class I MHC antigens. The SV40-transformed cells--cells transformed in vitro that produced tumors with equal efficiency in both syngeneic and allogeneic adult hamsters--or cells derived from SV40-induced tumors expressed very high levels of class I MHC antigens. The Ad12-transformed cells uniformly expressed low levels of class I MHC antigens; these cells produced tumors 200- to 1,000-fold less efficiently in allogeneic adult hamsters than in syngeneic adult hamsters and produced tumors with about the same efficiency in immunoimmature newborns and immunocompetent syngeneic adult hamsters. We conclude that the expression of either high levels or low levels of class I MHC antigens is, at most, a minor factor in the differences observed among these adenovirus- and SV40-transformed cells in their tumor-inducing capacity in naive, immunocompetent hamsters.

Adenoviridae↗
PubMed1987

Expression patterns of MHC class II genes in rabbit tissues indicate close homology to human counterparts.

Genomic clones corresponding to five distinct major histocompatibility complex class II alpha-chains have been described for the rabbit; four of these encode complete, potentially functional alpha-chains. Hybridization analysis and preliminary sequence analysis indicate that one of these clones is structurally related to HLA-DP alpha, one to -DR alpha, one to -DQ alpha and one to -DZ alpha. Probes specific for the four class II genes were used to screen RNA samples from normal rabbit tissues to determine which of these genes are transcribed and whether expression of any particular gene is tissue specific. All four of the genes are transcribed, but there are variations in the levels of expression, in tissue distribution, and in transcript size. The highest levels of RLA-DR alpha, -DQ alpha, and -DP alpha transcription were found in lymphoid tissues. Lower levels of transcription were also detectable in several nonlymphoid tissues. Transcripts observed were about 1.3 kb, a size expected for these class II alpha-chain genes based on experience with their human homologues. The RLA-DZ alpha probe corresponding to HLA-DZ alpha hybridized weakly with a band of 3.6 kb; its expression could be detected only in lymphoid tissues. The size of the DZ alpha transcript, its tissue distribution, and partial sequence data confirm its homology with the human gene DZ alpha. In blots of total cellular RNA, a probe for a recently described human beta-chain, DO beta, hybridized to a transcript of about 1.3 kb in lymphoid tissues. These data indicate that RNA transcripts corresponding to all HLA class II loci described to date can be detected in rabbit tissues.

Animals↗
PubMed1986

Partial amino acid sequence and genetic control of latent a2 allotype induced in rabbits by immunization with anti-a2 antibody.

We have shown that after immunization of homozygous a1 rabbits of the B immunoglobulin (Ig) heavy chain haplotype with anti-a2 antibody (Ab) a population of molecules appears that has all of the serologic characteristics of the a2 allotype. We have now isolated these putative latent a2 molecules, have separated the heavy chains, and after enzymatic deblocking, have determined the first 19 N-terminal amino acids. For all eight allotype-associated residues, these putative latent a2 molecules have the amino acid residues typical of a2 allotype. As expected, the preimmune IgG from this a1a1 rabbit has the amino acids typical of the a1 allotype. Thus by partial amino acid sequence analysis, we provide additional evidence that the latent a2 allotype can be induced in a1a1 rabbits of the B heavy chain haplotype by immunization with anti-a2 Ab. Rabbits of other heavy chain haplotypes were also immunized with anti-a2 Ab and were tested for their ability to synthesize latent a2 allotype. Thus far, a1a1 rabbits of the A, B, C, and I heavy chain haplotypes all synthesize latent a2 allotype. In contrast, a3a3 rabbits of the G and H heavy chain haplotypes did not synthesize latent a2 allotype.

Amino Acid Sequence↗
PubMed1986

Phagocytic rabbit cell lines expressing class II MHC products: establishment of cell lines by viral transformation.

Continuous rabbit macrophage-like cell lines were established after in vitro infection of spleen cells with either Simian virus 40, lymphotropic papovavirus or herpesvirus sylvilagus. These cell lines are characterized as morphologically similar to mature macrophages, esterase positive, and have unrearranged immunoglobulin genes. They possess macrophage functionality because they are highly phagocytic and are able to mediate an antibody dependent cell mediated cytotoxicity assay on chicken red blood cells. Northern blot analysis of total cellular RNA with a DQ alpha probe indicates that the cell lines constitutively express message for class II gene products. In addition, cell sorter analysis indicates that two of these lines display class II antigen at the cell surface.

Alkaline Phosphatase↗
PubMed1986

Tumorigenicity of hamster and mouse cells transformed by adenovirus types 2 and 5 is not influenced by the level of class I major histocompatibility antigens expressed on the cells.

Inbred hamster and mouse cells transformed by the nononcogenic adenovirus (Ad) serotypes, Ad2 and Ad5, are nontumorigenic in syngeneic adult animals, while cells from these species transformed by the highly oncogenic Ad12 are tumorigenic in such rodents. By immunoprecipitation and flow cytometry, cells from four of six Ad2- and Ad5-transformed hamster and mouse lines expressed high levels of cell-surface class I major histocompatibility complex (MHC) antigens, while cells from two of these six lines expressed low levels of cell-surface class I MHC antigens. The levels of class I MHC proteins expressed by cells from these latter two lines were comparable to the levels of cell-surface class I MHC proteins expressed by cells from Ad12-transformed hamster and mouse lines. Moreover, an Ad2-transformed line that had become highly oncogenic after in vivo adaptation showed the same high level of MHC expression as the nononcogenic parent. The amounts of class I mRNA, analyzed by RNA blotting, were, in general, consistent with the levels of class I antigens expressed on the surfaces of these cells. These results indicate that there is no correlation between the tumorigenicity in immunocompetent syngeneic adult rodents of Ad2- and Ad5-transformed hamster and mouse cells and the level of class I MHC antigens expressed on the surfaces of these cells. Thus, the expression of different levels of class I MHC proteins does not seem to explain the differences in the oncogenicity between nononcogenic and highly oncogenic human Ad serotypes.

Adenoviruses, Human↗
PubMed1985

Rabbit-mouse hybridomas secreting intact rabbit immunoglobulin.

Rabbit-mouse hybridomas offer the potential for production of monoclonal rabbit antibodies by immortal cell lines. In previous studies, it was possible to produce and stabilize rabbit-mouse hybrid cells secreting either a rabbit heavy or light chain. These have been useful for structural characterization of the individual rabbit immunoglobulin polypeptides and for isolation of large amounts of immunoglobulin mRNA for molecular studies. For some studies, however, it would be useful to have intact rabbit immunoglobulin molecules comparable to the myeloma proteins available in the human and mouse. The availability of rapid, sensitive and specific assays for rabbit heavy and light chains and allotypes located on specific chains has now permitted the early identification of clones secreting intact rabbit immunoglobulin. Vigorous cloning efforts have resulted in isolation and partial stabilization of three such clones. The first, H105, secretes a product with a kappa light chain bearing the b6 allotype and a mu-chain bearing the a1 allotype. Biochemical and serologic analyses of the product show that it is secreted as a fully assembled IgM pentamer and that the rabbit heavy and light chains are covalently associated. No rabbit J-chain gene was detected in H105 by Southern blot analysis. The second hydridoma, H134, secretes a product with a mol. wt of 150 K, consisting of a b4 light chain and an a1 heavy chain. The third, H171, secretes an alb4 IgG with antibody specificity for group C streptococcal carbohydrate. An additional rabbit-mouse hybridoma, H89, have been produced which secretes a rabbit heavy chain lacking group a allotypic activity. The rabbit heavy chain, which is associated with a mouse light chain, has an N-terminal amino acid sequence identical to a2-positive molecules although thorough serologic analysis revealed no group a allotypic activity.

Amino Acid Sequence↗
PubMed1977

The inheritance of antibody V regions in the rabbit: linkage of an H-chain-specific idiotype to immunoglobulin allotypes.

Anti-idiotype antibodies specific for the H chain of an homogeneous antistreptococcal antibody (4135 Ab) were prepared by injection of recombinant molecules consisting of the H chains from 4135 Ab and L chains isolated from the injected rabbit. The antibodies prepared in this fashion (anti-HId) were specific for the VH region of 4135 Ab. Using this preparation in an inhibition of binding assay, sera from rabbits related and unrelated to 4135 were screened for the presence of the 4135 HId. It was found that about 45% of the related rabbits, when immunized with streptococcal Group C vaccine, produced antibodies with a cross-reactive idiotype, while less than 10% of similarly immunized unrelated rabbits produced molecules bearing HId. The expression of HId was linked to the a3 allotype present in the H chain allogroup J. Antibody molecules bearing the HId determinant were isolated from heterozygous (a1a3 and a2a3) rabbits and shown to express the a3 allotype. One rabbit lacking the a3 allotype produced significant amounts of antibodies expressing HId. These antibodies were found to express both VH and CH allo-types characteristic of the J allogroup, although neither allotype was found in a preimmune IgG sample from this rabbit.

Animals↗
PubMed1977

The use of idiotypes as markers for antibody variable regions in the rabbit.

This article reviews the use of idiotypes as variable region genetic markers in the rabbit. Topics discussed include reagents and assays for the detection of idiotypes, evidence concerning the association of idiotypes with specific antigen binding sites on antibodies, and the inheritance of idiotypes in the rabbit. Several points are emphasized in this review. First, interpretation of idiotypic phenomenons are strongly dependent on the reagents and assays employed. Second, while strong evidence exists that a given idiotype is a marker for a specific antigen binding site, exceptions to this association have been reported. Third, the inheritance of identical or similar idiotypes has been demonstrated in several instances, but it is not always demonstrable, perhaps because an idiotype is a complex phenotype. Several reasons for this complexity are pointed out. Fourth, idiotypes are linked to group a allotypes and VL subgroups but exceptions to these associations have been described for antibodies isolated from single individuals. The significance of these exceptions is discussed. Current areas of interest in rabbit idiotypy include the relationship of idiotypes to other V region markers, the genetics of idiotypes specific to H or L chains, and the relationships among the idiotypes of antibodies isolated from a single rabbit.

Animals↗
PubMed1976

A genetic polymorphism in the constant region of rabbit b4 kappa chains.

Amino acid sequence analysis of a b4 light chain from a rabbit homogeneous antistreptococcal antibody revealed the presence of two amino acid substitutions in the constant region not previously reported for these positions. These interchanges, consisting of serine for alanine at position 121 and leucine for glutamine at position 124, were also present in about 30% of the pooled b4 light chains isolated from pooled IgG from the rabbit (4539) that produced the homogeneous antibody. In addition, these interchanges (b4var) were found, always at the same levels, in varying percentages in nonimmune or early immune bleedings from related rabbits in this pedigreed family and could be traced for five generations. The inheritance pattern of b4var was consistent with autosomal codominant inheritance.

Amino Acid Sequence↗
PubMed1976

Structure of the peptide antibiotic polypeptin.

Polypeptin, a basic peptide antibiotic isolated from Bacillus circulans, was separated into two components by countercurrent distribution. The two components, polypeptin A and polypeptin B, had identical amino acid compositions but varied in the structure of the hydroxy acid constituent attached to the alpha-amino group of the peptide chain. Polypeptin A contained 3-hydrosy-4-methylhexanoic acid and polypeptin B contained 3-hydrosy-5-methylhexanoic acid. T-HE STEROCHEMISTRY OF THESE HYDROXY ACIDS WAS NOT DETERMINED. Studies involving partial acid hydrolysis and chemical synthesis are consistent with the lactone sturcture for polypeptin A. Polypeptin B differs only in the position of the methyl group in the hydroxyacyl moiety.

Amino Acid Sequence↗
PubMed1976

Isolation and characterization of rabbit antibodies directed against group a allotypic determinants.

The L chains of rabbit antibodies directed against group a allotypes exhibited in many instances a high degree of homogeneity as measured by L chain banding patterns in alkaline urea polyacrylamide gels. Amino terminal sequence analyses were carried out on six L chain preparations from antibodies isolated from individual antisera or from pools of antisera. The same major amino terminal sequence, Ala-Val-Val-Met, was observed for each of these preparations indication that anti-allotype antibodies preferentially select L chains from a single subgroup. The antiallotype anitbodies were isolated from antisera by elution from IgG immunoadsorbent columns in yields ranging from 0.3 to 1 mg/ml antibody. The specificity of the isolated antibodies was demonstrated by radioimmune assays. Certain fractions were contaminated with a protein that had properties similar to rabbit serum albumin. This contamination was minimized by preadsorption of the antisera. The antibodies were primarily of the IgG class as shown by immunoelectrophoresis and by m.w. of the H and L chains on SDS gels.

Adsorption↗