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Biomedical subjects

A Gilman-Sachs

Publications and source records attributed to A Gilman-Sachs.

At least 55 records · Page 3Linked to original sources
PubMed1991

Influence of aging, environmental antigens, and dietary restriction on expression of lymphocyte subsets in germ-free and conventional Lobund-Wistar rats.

Lymphocyte subsets from four groups of Lobund-Wistar (L-W) rats were quantitated to determine the influence of diet restriction (DR) and exposure to environmental antigens on the development of these cells. The following effects were found from 6 to 30 months of age: The number of Ts/c and Ts cells were higher in germ-free (GF) vs conventional (CV) rats, whereas B-cell numbers were lower. W3/13 T cells, Ts, and NK cell numbers were higher in DR vs full-fed rats, whereas B-cell numbers were lower. OX19 and W3/13 T cell numbers decreased from 6 months to 30 months in each group, whereas NK cell numbers increased. Also, OX6+ B cell numbers increased with age, and Ts/c numbers decreased. These data may reflect a relationship between enhanced T-cell function and the extended life span and lower tumor incidence observed in DR L-W rats.

Aging↗
PubMed1991

Patterns of anti-phospholipid antibody specificities.

To determine the importance of assaying for anti-phospholipid (PL) antibodies other than anti-cardiolipin antibodies in patients with putative anti-phospholipid antibody syndrome (APA), 1,513 serum samples from over 399 patients with the potential for thromboembolic disease were tested for IgM, IgG or IgA class antibodies to the following phospholipids: cardiolipin, phosphatidylserine, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidic acid. Non-specific binding was subtracted from total binding of antibodies to each PL to eliminate false positive ELISA results. Only patients whose sera contained antibody levels which were greater than three standard deviations above the means were considered positive. Patients who were positive for anti-PL antibody had antibodies to at least one of six phospholipids tested. Approximately 60% of the positive samples contained antibodies to a phospholipid other than cardiolipin. For IgG class, antibodies to phosphatidylserine were the most prevalent followed by antibodies to phosphatidylethanolamine and cardiolipin. These findings indicate that anti-phospholipid antibody analysis should be performed for more than anti-cardiolipin antibody to detect patients with APA.

Abortion, Habitual↗
PubMed1991

DNA flow cytometry of colorectal carcinoma: correlation of DNA stemlines with other prognostic indices.

DNA flow cytometry (FCM) was performed on paraffin-embedded tissue blocks of 38 surgically resected colorectal carcinomas (CRC). Forty-seven percent of tumors exhibited aneuploidy and 53% were diploid. Seventy-two percent of patients in the aneuploid but only 35% in the diploid group were alive after a mean follow-up of 30.7 and 28.8 months (p = 0.01), and 5-yr survival of 56.7% and 11.7%, respectively (p less than 0.05). The site of tumor location, Dukes' stage, and serum CEA level did not predict a certain DNA stemline. However, irrespective of the ploidy pattern, a serum CEA level greater than 5.0 was associated with a higher mortality and poor 5-yr survival (p less than 0.005). Similarly, advanced Dukes' stage was associated with higher mortality (p less than 0.05). Forty-six percent of the patients with lesions that were Dukes' B2 or advanced stage received adjuvant therapy. Eighty-five percent of this subgroup of patients died; 18% of these patients had aneuploid tumors. The role of FCM in the assessment of prognosis of CRC deserves further clinical evaluation in a randomized control trial.

Adult↗
PubMed1990

Inhibition of binding of anti-CD3 antibodies to paternal lymphocytes correlates with failure of immunotherapy for treatment of recurrent spontaneous abortions.

A two color flow cytometry crossmatch (FCXM) was used to evaluate the induction of anti-lymphocyte antibodies in 34 women undergoing immunotherapy for recurrent spontaneous abortions. All women had anti-lymphocyte antibodies that reacted with T-cells when analyzed by FCXM. However, inhibition of the binding of anti-CD3 to paternal CD3 lymphocytes in the presence of maternal antipaternal lymphocyte antiserum was found for some couples following lymphocyte immunotherapy for spontaneous recurrent abortions. Ten couples who had another spontaneous abortion following immunotherapy showed inhibition. In contrast, eight couples who did not show inhibition of the binding of anti-CD3 T lymphocytes to paternal lymphocytes by maternal anti-lymphocyte antiserum had live births. Women of the remaining 16 couples were either pregnant and awaiting birth or not pregnant. Thus, by FCXM it may be possible to predict those couples who will have successful pregnancies following this treatment.

Abortion, Habitual↗
PubMed1989

Flow cytometric analysis of lymphocyte subsets in peripheral blood of chronic headache patients.

Lymphocyte subsets from 5 groups of patients with different types of chronic headaches were analyzed by flow cytometry to determine the number of cells bearing the following markers: T11 (E-rosette receptor), T3 (total T cells), T4 (T-helper/inducer cells), T8 (T-cytotoxic/suppressor cells), B1 (B-cells), NKH-1 (Natural killer cells), I2 (Class II histocompatibility antigens, monomorphic determinants) and Mo2 (monocytes). In 4 of 5 of these groups, the absolute number of T8 lymphocytes was significantly lower than that of control group. In addition, the T4:T8 ratio was higher in these 4 groups. These findings may suggest a relationship between the immune system and the cause of chronic headaches.

Antibodies, Monoclonal↗
PubMed1989

Analysis of anti-lymphocyte antibodies by flow cytometry or microlymphocytotoxicity in women with recurrent spontaneous abortions immunized with paternal leukocytes.

The identification of anti-lymphocyte antibodies was investigated in women with a history of recurrent spontaneous abortions who received leukocyte immunization treatment. The antibodies were detected by two-color flow cytometric analysis (FCMX) and by microlymphocytotoxicity (MCX). Twice the number of positive patients (women who had been immunized with paternal leukocytes and produced antilymphocyte antibodies) could be identified by flow cytometry versus a standard microcytotoxicity assay (66 versus 33%). In addition, when mixed lymphocyte culture assays were performed to determine if serum blocking factors had been induced, those couples who were positive by FCMX showed inhibition of the mixed lymphocyte culture responses in contrast to most FCMX negative patients who did not. Thus, the sensitivity of the FCMX and its rapidity makes it an alternative to the mixed lymphocyte culture assay for assessing immunotherapy in women with recurrent spontaneous abortions.

Abortion, Habitual↗
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↗
PubMed1985

Allotypic and isotypic specificities of rabbit IgM: localization to the Fab mu or Fc mu fragments.

IgM from trypanosome-infected rabbits was digested with trypsin under different conditions to obtain Fab mu or Fc5 mu fragments suitable for analysis with anti-allotype and anti-isotype antibodies. The Fab mu but not the Fc5 mu fragment was shown to have the n-locus allotypic specificities, n80, n81, n82, n83 and n87, characteristic of the IgM class of immunoglobulins. Thus, the n82 and n83 allotypic specificities, conformationally dependent on the a VH locus for expression, and the n80, n81 and n87 allotypic specificities, independent of the a VH locus for expression, are in either the CH1 or CH2 domain of IgM heavy chains. In addition, two high-affinity mouse monoclonal antibodies (MoAbs) specific for IgM and able to bind IgM in direct-binding radioimmunoassays were produced and characterized. One MoAb (3C1) was specific for an isotypic determinant (epitope) in the Fab mu fragment, presumably in the CH1 or CH2 domain, whereas another MoAb (8C2) was specific for an isotypic epitope in the Fc5 mu fragment, presumably in the CH3 or CH4 domain. The proximity of the n-locus allotypic specificities (CH1 or CH2 domain) to the VH domain is consistent with the finding that some IgM allotypic specificities are expressed only in conjunction with certain a VH locus allotypic specificities.

Animals↗
PubMed1984

Induction of "latent a2" allotype in a1a1 homozygous rabbits as the major part of a bidirectional immune response to immunization with anti-a2 antibody.

Previously, we induced Ab to a common idiotypic specificity (IdC) of rabbit anti-a2 VH Ab. We observed then that some of the putative anti-IdC Ab molecules induced by immunizing a1a1 rabbits with anti-a2 Ab did not have the expected nominal allotypic markers (a1, x32, or y33) characteristic of the genotype of the immunized rabbits. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab induced population of molecules that reacted with anti-a2 Ab but bore an unidentified (unknown) VH region marker. The following observations indicate that these molecules bear a "latent a2" allotypic marker: (a) when the unknown VH molecules were used to immunize a1 a1 and a3 a3 rabbits, anti-a2 Ab was produced; (b) when an a2 a2 rabbit was immunized with the same preparation of unknown VH molecules, an anti-idiotypic Ab was produced; and (c) when the unknown VH molecules were used to inhibit the binding of labeled a2 IgG to anti-a2 Ab, the inhibition curve obtained was essentially the same as that obtained by using normal a2 IgG. Thus, immunization of a1 a1 rabbits with a1 anti-a2 Ab provided a bidirectional stimulus to produce both nominal "a1" anti-IdC Ab and a "latent a2" allotype. The distribution of nominal to latent allotypes induced ranged from 3% nominal/92% latent to 57% nominal/23% latent. In absolute terms, the maximum amount of "latent a2" molecules was 1.18 mg/ml of serum, which far exceeds the amount of latent allotype described by others (0.3 mg/ml of serum). The effective induction of large amounts of "latent a2" allotype may have resulted from a simultaneous stimulation of an idiotope and a paratope on the surface of the "latent a2"-producing cells.

Animals↗
PubMed1983

The common idiotypic specificity of anti-a2 allotype antibodies: contribution of H and L chains to idiotype expression.

Previously an idiotypic specificity common to anti-a2 allotype Ab from 15 rabbits was detected and characterized. The contribution of H and L chains to the expression of this common idiotypic specificity was determined. Two types of recombinant IgG were prepared: (1) H chains from anti-a2 Ab with L chains from normal a3b4 IgG, and (2) L chains from anti-a2 Ab with H chains from normal a3b4 IgG. By inhibition of binding radioimmunoassay, recombinant IgG having either H or L chains from anti-a2 did not inhibit the binding between anti-a2 Ab and anti-idiotype Ab. By direct binding radioimmunoassay, recombinant IgG of H chains from anti-a2 Ab with L chains from a3b4 IgG reacted with anti-idiotype Ab whereas recombinant IgG with H chains from normal a3b4 IgG and L anti-a2 Ab is determined primarily by the H chain; however, the full expression of the common idiotypic specificity requires the interaction of both H and L chains from anti-a2 Ab.

Animals↗
PubMed1982

Rabbit heavy chain haplotypes--allotypic determinants expressed by VH-CH recombinants.

This report summarizes our current understanding of the heavy chain haplotypes found in our laboratories' rabbits. Independently derived data from several laboratories have been synthesizes into a consistent picture of the linked inheritance of allotypic markers found on the different heavy chain classes and subclasses of rabbit immunoglobulins in pedigreed rabbits, including the families of three apparent VH-CH recombinants. In one recombinant, the entire group of CH markers (C mu, C gamma, and C alpha) recombined with the set of VH. Although in the other two recombinants all CH markers may also have recombined as a group, in one of these only IgG and IgA CH genes were informative; in the other recombinant, only the IgG allotypes were informative. Some allotypic determinants found on IgM molecules ("conformational") appear only when a specific variable region allotype (VHa) is combined with a specific mu constant region allotype (C mu). New combinations of VHa and C mu allotypes were generated in two of the genetic recombinants and led to new "conformational" determinants. The gains and losses observed lend support to the hypothesis that the determinants result from conformations generated by the combination of allotype-specific VH and C mu protein sequences. Conceivably, DNA events that join VH to diversity (D)- and joining (J)-coding sequences or mRNA processing events that splice J to C mu could be involved in generating the sequences that form allotype-specific determinants.

Animals↗
PubMed1982

An increase in the number of recombinant molecules and other effects of the simultaneous allotype suppression of trans-chromosomal a VH and n Cmu Ig gene products.

The concomitant effects of trans-chromosomal allotype suppression of both an a VH and an n Cmu locus allotype in multiheterozygous rabbits were investigated. For example of the expression of the a2 VH and n81 Cmu allotypes were suppressed in a multiheterozygous rabbit having the a1 chi-y-n81de12,15f73g74/a2 chi 32y33n80de12.14f69g77 genotype. This trans-chromosomal allotype suppression led to the concomitant suppression of other CH allotypes in the same parental haplotype as the suppressed-n81 allotype (i.e. the e15, f73 and g74 allotype) and the partial suppression of the a1 VH allotype (from the normal level of 70% of the total Ig to 10%), and also led to compensation by other VH allotypes from the same parental haplotype as the suppressed-a2 allotype (i.e. the x32 and y33 allotypes). The x32 and y33 allotypes were expressed on Ig molecules with the CH allotypes coded by the same haplotype (i.e. the cis molecules). In a further analysis of the IgG molecules having the partially-suppressed-a1 allotype, one-half (5%) of these molecules were trans-chromosomal recombinant molecules (i.e. a1e14 IgG) and the other half (5%) were cis-chromosomal molecules (i.e. a1e15 IgG). The trans-chromosomal a1e14 IgG molecules probably were derived from the expansion of a limited number of lymphoid clones that normally produce only 1.5% trans-chromosomal recombinant molecules. The cis-chromosomal a1e15 IgG molecules were probably derived either from lymphoid clones that survived the suppression by the anti-n81 Ab, or from lymphoid clones that bore a different subclass of IgM (i.e. n-negative IgM).

Animals↗
PubMed1981

Genetic control of the expression of allelic Ig genes at the VH a locus in a1/a2 heterozygous rabbits.

Heterozygous rabbits representing 9 of 15 possible a1 and a2 heavy chain haplotype gene combinations among rabbits in the University of Illinois colony were analyzed for ratios of a1 to a2 in serum immunoglobulin (Ig). The Ig from rabbits of the a1x-y-n81f73g74de12,15 heavy chain haplotype in combination with any of three a2-associated heavy chain haplotypes have higher ratios of a1 to a2 than Ig from rabbits in which a1 is encoded by 4 other heavy haplotypes. For example, the mean a1:a2 ratio for adult a1x-y-n81f73g74de12,15/a2x32y33,- n82,f71g75de12,15 rabbits was 12:1 compared to 5:1 for a1x-y33,30n83,f71g75de12,15/a2x32y33,- n82,f71g75de12,15 heterozygous rabbits. Family studies indicated that the a1:a2 ratio was under the control of the heavy chain chromosomal region or a locus closely linked to it. Whether the regulation is due to varying numbers of VH genes and/or J gene segments, a separate regulator gene, or more efficient joining of certain gene segments, has yet to be determined.

Alleles↗