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Biomedical subjects

R Lieberman

Publications and source records attributed to R Lieberman.

At least 109 records · Page 6Linked to original sources

Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance.

Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.

Animals↗

Murine plasma cells secreting more than one class of immunoglobulin heavy chain. II. SAMM 368--a plasmacytoma secreting IgG2b-kappa and IgA-kappa immunoglobulins which do not share idiotypic determinants.

SAMM 368 is a BALB/c plasmacytoma which secretes IgG2b-kappa and IgA-kappa paraproteins. Immunofluorescence studies of ascites cells from the tumor with purified, heavy chain class-specific antiglobulins demonstrate that single cells contain both IgG2 and IgA heavy chains. Idiotypic antisera prepared in mice and rabbits indicate that the two paraproteins produced by the tumor do not share idiotypic determinants. Analysis of the purified paraproteins for allotype markers showed that SAMM 368 IgA bears the BALB/c A12,13,14 determinants. SAMM 368 IgG2b does not carry any detectable allotypic determinants in spite of the fact that heterologous antisera identify the paraprotein as IgG2b.

Amino Acid Sequence↗

Fifteen years experience with artificial insemination.

Artificial insemination is today an accepted procedure in circumventing sterility. In recent years this procedure gained much popularity as the number of infants available for adoption steadily decreased due to the liberal abortion laws. A review of 15 years of practiced experience (senior author) is presented. In all described cases (168 women) artificial insemination was performed personally by the author. The high rate of success (80% of the presented cases) is attributed to a very meticulous and highly individualized approach to each case. Review of literature is presented.

Adolescent↗

Idiotype of inulin-binding antibodies and myeloma proteins controlled by genes linked to the allotype locus of the mouse.

The serum from non-immunized mice of strains BALB/c, C58, A/He, and RIII contained hemagglutinins for stearoyl inulin-coated SRBC. Immunization with bacterial levan slightly elevated these titers. These same sera also carried cross-specific idiotypic determinants (IdX) that are associated only with inulin-binding myeloma proteins (INBMP) of BLAB/c mice. Three InuldX specificities, A, B, and G, were identified. The InuIdX phenotypes of strains BALB/c, C58, and A/He were InuIdXA+B+G+; strain RIII was InuIdX A+B-G+; strain C57BL/6, C57BL/10, DBA/2, AKR and NH were A-B-G-. Strains CBA, C3H, PL, and C57L could not be typed because of low and inconsistent levels of InuIdX and anti-inulin hemagglutinins. The InuIdXA+B+G+ phenotype was used as a genetic marker in immunoglobulin congenic strains CB-20, BAB-14, and BC-8 and in Bailey RI strains which are derived from crosses of BALB/c (InuIdXA+B+G+) and C57BL/ka or C57BL/6, respectively (InuldXA-B-G-). Linkage of the IdXA+B+G+ to the BALB/c a allotype locus was demonstrated. In addition, the InuldXA+B+G+ marker was used as a phenotype in an analysis of 168 first generation backcorss progeny (C57BL X (C57BL X BALB/c) F). Linkage of the marker to the BALB/c allotype was found again. Two proven recombinant mice having the C57BL a allotype and the InuIdxA+B+G+ markers were identified and progeny tested. Four other potential crossover types are still being progeny-tested.

Animals↗

Multiple individual and cross-specific indiotypes on 13 levan-binding myeloma proteins of BALB/c mice.

13 leven-binding myeloma proteins (LBMP) of BALB/c origin were classified into two groups with different binding specificities; one group of 11 proteins bound beta2 leads to 1 fructosans, a second group of two proteins bound fructosans probably of beta2 leads to 6 linkage. Anti-idiotypic sera prepared to 10 of the proteins in the appropriate strains of mice identified numerous idiotypic determinants. Each protein used for immunization had its own unique individual idiotypic specificities (IdI) and in addition most of the proteins carried two-nine cross-specific or shared idiotypes (IdX) that were found only among LBMP, and not found in 106 non-LBMP. Most of the IdX determinants and only four of the IdI determinants of the beta2 leads to 1 fructosan binding group were located in the antigen-binding site. The multiplicity of antigenic differences in this functionally related group of immunoglobulins reveals an unexpected degree of heterogeneity in V-regions that appears to be unrelated to binding.

Animals↗

The immunologic and histopathologic changes of BCG-mediated tumor regression in patients with malignant melanoma.

Six patients with intradermal metastases of malignant melanoma were treated with intralesional bacile Calmette-Guérin (BCG). Four patients showed a good response with regression of injected, and in some cases, uninjected lesions, whereas two developed metastatic viscereal disease and died. Three of the six patients had complete regression of all lesions, and one exhibited complete regression of untreated lesions. All remain free of disease. The fourth patient had complete regression of injected and of some untreated lesions, but developed widespread dissemination and died. Preliminary experiments suggest the presence of a blocking factor in his sera which abrogates the lymphocyte stimulation in response to melanoma antigens. Three of four responders (i.e. those patients in whom treated lesions decreased in size by more than 50% for more than 1 month) showed a dramatic increase in lymphocyte stimulation to melanoma antigens. All responders (four out of four) had a marked increase to phytohemagglutinin (PHA), whereas non responders had no increase in lymphocyte stimulation either to melanoma antigens or PHA. Two of four responders showed inhibition of leukocyte migration to melanoma antigens before BCG, and two of four responders were positive after BCG. Of the nonresponders, one was positive and one negative before BCG; this remained the same after. There was a marked increase in active rosette forming cells in all responders and in one of the two nonresponders. Histopathologic studies at 3 hours, 6 hours, 24 hours, 14 days, and 4 weeks after BCG showed a definite sequence of events occurred, progressing from 1) inflammatory cell response at the periphery of the lesion, disruption of melanogenesis, extensive dumping of pigment from melanoma cells, proceeding to actual cell death at 24 hours, to 2) macrophages containing melanin and granulomas replacing tumor by 2 weeks. These studies suggest that BCG activates both specific and nonspecific immune responses. Thus, in vitro parameters of cellular immunity, including migration inhibitory factor production and inhibition of leukocyte migration, are affected by intralesional BCG, and some, particularly the lymphocyte stimulation and rosette test, seem to correlate with the clinical response of the patients.

Aged↗

Ontogeny of B lymphocytes. 3. H-2 linkage of a gene controlling the rate of appearance of complement receptor lymphocytes.

The frequency of lymphocytes bearing complement receptors in the spleens of 2-wk old mice appears to be controlled by two independent genes. The presence of a "high" allele at either locus leads to intermediate or high frequency of CRL at 2 wk of age. One of the genes controlling complement receptor lymphocyte (CRL) frequency (CRL-1) is linked to the H-2 complex. Thus, in progeny of (AKR x DBA/2)F(1) x DBA/2, all mice with a low frequency of CRL at 2 wk of age are homozygous for the H-2 type of the low CRL parent (DBA/2). Furthermore, in the B10 series of congenic mice, CRL frequency at 2 wk of age is similar to the frequency in the donor of the H-2 region. Thus, C57BL/10, B10.BR, and B10-D2 mice are all of the low CRL type while B10.A mice are intermediate in CRL frequency at 2 wk. C57BR and DBA/2, the donors of the H-2 complex of the B10.BR and B10.D2, respectively, are of low CRL type while the A/WySn, the donor of the H-2 complex in the B10.A, is an intermediate CRL strain. Similarly in the A/WySn series of congenic mice, A.CA, A.SW, and A.BY are all low CRL strains while the A/WySn is intermediate. Studies of CRL frequency in mice with recombinant H-2 chromosomes (B10.A(2R), (4R), and (5R); B6/TL(+); and A/TL(-)) indicate that CRL-1 is to the right of the Ss-Slp genes and to the left of Tla.

Age Factors↗

Genetics of a new IgVH (T15 idiotype) marker in the mouse regulating natural antibody to phosphorylcholine.

The idiotype present on the Fab of a phosphorylcholine-binding IgA myeloma protein TEPC 15 (T15) of BALB/c origin was found in normal serum of BALB/c mice. Molecules carrying the T15 idiotype in normal serum could be adsorbed with Sepharose phosphorylcholine beads and R36A pneumococci. The T15 idiotype is absent in germ-free BALB/c but appears when the mice are conventionalized. A survey of normal sera of inbred strains for the T15 idiotype showed it to be present in BALB/c, 129, C57L, C58, and ST and absent or in low levels in CBA, C3H, C57BL/6, C57BL/Ka, C57BL/10, SJL, B10.D2, DBA/2, RIII, A, AL, AKR, NZB, and NH inbred strains of mice. The T15 idiotype is associated with some but not all strains carrying the IgC(H) allotypes found in BALB/c. Linkage of genes controlling the T15 idiotype in normal serum to the IgC(H) locus of BALB/c was demonstrated in F(2) progeny of a BALB/c and C57BL cross, Bailey's recombinant inbred strains, C x BD, C x BE, C x BG, C x BH, C x BI, C x BJ, C x BK, and CB20 congenic strains. Among these strains, only those possessing the IgC(H) locus of BALB/c including the F(2) progeny consisting of BALB/c homozygotes and BALB/c/C57BL heterozygotes and C x BG and C x BJ recombinants showed the T15 idiotype.

Animals↗

Clonal nature of the immune response to phosphorylcholine. I. Specificity, class, and idiotype of phosphorylcholine-binding receptors on lymphoid cells.

The relationship between receptor molecules on antigen-binding lymphocytes (ABC) and antibody produced by antibody-secreting cells was studied in inbred strains of mice using the immune response to phosphorylcholine (PC) as a model system. Splenic and lymph node lymphocytes of nonimmune mice possess rare lymphocytes which bind (125)I-labeled PC-bovine serum albumin. The frequency of PC-ABC increases after immunization and is paralleled by a rise in the frequency of PC-specific antibody-producing cells. Both of these responses are thymus independent. The receptors on these ABC display specificity for PC and are exclusively of the IgM class. In one of the strains, BALB/c, the receptors possess the same idiotype and fine degree of specificity for PC and two of its analogues, glycerophosphorylcholine and choline, that are characteristic of a PC-binding myeloma, HOPC 8. Furthermore, the idiotype and class of the receptor in these mice do not change during the course of the immune response. These data provide more direct evidence for the immunelogic relevance of receptor-bearing lymphocytes.

Animals↗

Cytogenetic engineering in vivo: restoration of biologic complement activity to C5-deficient mice by intravenous inoculation of hybrid cells.

Splenic macrophages were identified as at least one source of C5 elaboration in normal mice. Hybrid cells were formed from splenic macrophages from C5-deficient mice and either kidney cells from mice with normal amounts of C5 or chicken erythrocytes. These hybrids elaborated C5 in vitro. C5-Deficient mice inoculated with these hybrid cells developed, in their serum, antigenically active mouse C5, as well as both hemolytic and biologic complement activity. These studies demonstrate the feasibility of genetic "repair" in mammals.

Animals↗

Association of H-2 types with genetic control of immune reponsiveness to IgG (gamma2a) allotypes in the mouse.

Immune responsiveness to IgG allotypes in the mouse was found to be controlled by an immune response gene Ir-IgG linked to the H-2 locus. This was demonstrated by the analysis of the immune response to BALB/c IgG (gamma2a) myeloma proteins in mice of various H-2 types from five different linkage groups of immunoglobulin heavy chains. Antisera were examined for antibodies to idiotypic (Fab) and allotypic (Fc) specificities. No immune response to BALB/c IgG myeloma proteins was found in mice with the same heavy-chain immunoglobulin linkage group as BALB/c but of different H-2 types. In mice with immunoglobulin heavy chains that are different than BALB/c, a high immune response to IgG myeloma proteins was found in H-2 types b, bc, p, r, s, and v; a low response in a, d, k, and q. The Ir-IgG gene is controlled by a dominant autosomal gene.

Animals↗