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S Segal

Publications and source records attributed to S Segal.

At least 361 records · Page 20Linked to original sources
PubMed1983

Splenic B cells function as immunogenic antigen-presenting cells for the induction of effector T cells.

Previous studies performed in our laboratory have revealed that an ordered, sequential, tricellular interaction is obligatory for the antigen-driven induction of a specific effector memory T cell. Thus, it was found that antigen-pulsed peritoneal macrophages signal, in spleen cells, the generation of antigen-specific initiator lymphocytes. These lymphocytes, following injection to syngeneic recipients, recruit, in the draining lymph nodes, "virgin" antigen-reactive T lymphocytes. Although the nature of the first and last cell in the interacting sequence was well characterized, the identity of the intermediary initiator splenic cell was obscure. Studies were carried out to characterize the nature of the splenic initiator cells. It was found that spleen cells from nu/nu, adult thymectomized and neonatal thymectomized, or spleen cells from normal donors which had been subjected to cytolysis using anti-Thy-1.2 antibodies in the presence of complement, did generate, following interaction with keyhole limpet hemocyanin (KLH)-fed macrophages, specific initiator cells. Carrageenan impairment of spleen macrophages did not affect the generation of initiator cells, nor did the depletion of dendritic cells from the spleen. On the other hand highly enriched B cell, but not highly enriched T cell populations, when seeded on KLH-pulsed macrophages, generated antigen-specific initiators, which, in vivo, recruited antigen-reactive T cells. It thus appeared that B lymphocytes can function as intermediary obligatory antigen-presenting cells and actively transfer immunogenic signals from peritoneal antigen-presenting cells to T lymphocytes. These findings may therefore suggest that antigen-specific B cells do not function solely as antibody-producing cells, but, once activated by macrophages, may control the induction and differentiation of some antigen-reactive T cell subsets. Thus, one can view the B cell as an important regulatory cell of both cellular and humoral immune functions. The significance of this observation with regard to Ir gene control at the level of B lymphocytes is discussed.

Animals↗
PubMed1983

Defective induction of antigen-reactive proliferating T cells in B cell-deprived mice. II. Anti-mu treatment affects the initiation and recruitment of T cells.

Mice injected from day of birth onwards with rabbit anti-mouse IgM (antim-mu) antibodies were found to be B cell-deficient and defective for the induction of antigen-reactive proliferating T cells (TPRLF). This defective induction was not due to the absence of circulating antigen-specific antibodies since the daily injections of such antibodies during exposure to antigen did not restore the ability of anti-IgM treated animals to generate TPRLF. Analyzing the cellular events implicated in the induction of virgin antigen-reactive T cells, anti-mu-treated mice manifested impairment of the three interacting cell types involved in the induction of TPRLF. Thus, peritoneal and splenic antigen-presenting cells from such animals were impaired in their capacity to signal a primary antigen-specific T cell reaction. Their splenic lymphocytes could not function as initiator cells in transferring immunogenic signals to recruit TPRLF in normal recipients. Potent antigen-specific splenic initiator cells failed to induce the recruitment of specific TPRLF in anti-mu-treated mice. The defective induction of TPRLF in anti-mu-treated mice may be due to a functional impairment of cells expressing membrane-bound IgM molecules which seemingly play a central role in the transfer of immunogenic signals for the recruitment of antigen-specific circulating T cells. We suggest that splenic B cells function as initiators in the transfer of antigen-induced signals from peritoneal antigen-presenting cells to T cells. These seems to be the primary targets of anti-mu treatment.

Animals↗
PubMed1983

Differences in the metastatic potential of two sublines of tumor 3LL selected for resistance to natural NK-like effector cells.

Normal syngeneic spleen cells were found to inhibit the local growth of the Lewis lung carcinoma (3LL) when injected together with the tumor cells at a ratio of 100:1 (spleen to tumor cells). The repeated injection of the tumor cells together with spleen cells eventually led to the selection of a tumor cell population whose growth could no longer be inhibited by normal spleen cells. In a previous report from this laboratory, a tumor subpopulation obtained in this manner was shown to display an increased metastatic potential, as well as a decreased sensitivity to natural resistance mechanisms in vivo and NK lysis in vitro. In the present study, we attempted to characterize the spleen cell population which mediated this selection process. We found that spleen cells depleted of T cells, B cells, or adherent macrophages retained their ability to inhibit tumor growth and select a resistant line in vivo. Subsequently, two tumor sublines derived by continuous in vivo passage of the parental tumor line with either unfractionated or nylon wool-non-adherent spleen cells were characterized. It was found that whereas both sublines were resistant to growth inhibition by normal spleen cells, only the subline derived from continuous passage with unfractionated spleen cells showed a reduction in the density of H-2b molecules expressed on the cell surface and an enhanced metastatic potency. These results suggest that the resistance of a tumor line to natural killer cells may not always result in an increase in its metastatic potential.

Animals↗
PubMed1983

Fresh and cryopreserved fetal bones replacing massive bone loss in rats.

Cartilaginous fetal bones from rat preserved by deep freezing procedures were compared to comparable fresh bones with regard to the following parameters: chemical composition, water and uronic acid contents; cell viability measured by the rate of proteoglycan synthesis; mineralization-ossification status by calcium binding; matrix integrity by the release of uronic acid containing substances; and biological activity as transplants inducing the formation of bone. The transplanted material was chemically analyzed and checked for its rate of proteoglycan synthesis. The quality of the formed bone was similar whether isogeneic or allogeneic, fresh or cryopreserved bone was employed as transplant material. Evidently those various fetal bones may be of clinical value whenever the need for replacement of massive bone loss arises. Although the viability and the cartilaginous nature of the graft are critical, the isogeneity and freshness are of a quantitative advantage only. These biochemical observations were confirmed by roentgenological and histological evaluations of the grafts. An optimal cryopreserving procedure and tests for examining bone candidates for successful grafting are described.

Animals↗
PubMed1983

Rapid determination of [guanidino-15N]arginine in plasma with gas chromatography--mass spectrometry: application to human metabolic studies.

A rapid gas chromatographic-mass spectrometric method for the determination of 15N in the guanidino nitrogens of arginine is described. The method is based on formation of the N-tetratrifluoroacetyl-arginine derivative. Approximately 0.15 mol% excess 15N can be detected in as little as 50 microliters of plasma with an average coefficient of variation of 8.8%. The possible fragmentation pattern of the N-tetra-trifluoroacetyl-arginine derivative is described. The method was applied to determine the appearance of 15N enrichment in plasma arginine in a healthy adult volunteer during a constant infusion of 15NH4Cl. A plateau level of 0.7 atom% excess was observed 2 h after the 15NH4Cl infusion was started.

Acetic Anhydrides↗
PubMed1983

High-performance liquid chromatography of phospholipids: quantitation by phosphate analysis.

Quantitation of individual phospholipids separated by HPLC from tissue extracts by colorimetric analysis of phosphate was investigated. Elution of inorganic phosphate and breakthrough of lecithin were determined using radioisotopes. A substance which interfered with sample phosphate determinations was found in the column eluant, and a method to minimize its effect was developed. This method allows accurate quantitation of individual phospholipids present at a minimum of 20 nmol phosphate.

Animals↗
PubMed1983

A model for determination of total body protein synthesis based upon compartmental analysis of the plasma [15N] glycine decay curve.

A model for whole body glycine nitrogen flux based on the compartmental analysis of plasma [15N] glycine decay curves is described and used for the measurements of (1) total body glycine nitrogen flux and the components of this flux in three healthy young adults and (2) total body protein synthesis based on the conversion of 15N to excretory products, ie, the sum of urinary [15N] urea and 15NH3 and the amount of labeled urea remaining in the body at five hours following administration of [15N] glycine. The mean glycine nitrogen flux was 3.93 +/- 0.42 mg N X kg-1 X h-1 (SEM). The major components of this flux are de novo synthesis of glycine, which accounts for 18% to 27%, and release from protein breakdown, which accounts for 62% to 73%. The outward pathways of glycine from the total body free glycine pool are conversion to other amino acids and oxidation to excretory end products (30% to 42%) and incorporation into protein, which accounts for 45% to 61% of glycine N loss from the metabolic pool. The mean rate of total body protein synthesis as determined by compartmental analysis was 3.56 g protein X kg-1 X day-1. The results that were obtained for protein synthesis and whole body glycine kinetics accord well with previous studies in normal adults, using the stochastic model.

Adult↗
PubMed1983

Effect of chloroquine on handling of cystine by cystinotic fibroblasts.

Cystinotic fibroblasts when incubated in complete medium with 100 microM chloroquine rapidly lose their stored cystine, 50% or more disappearing in 2 hr and 80% in 4 hr. During the same 2 to 4 hr period of incubation with chloroquine, no change in intracellular pools of acidic and neutral amino acids was observed. However, after 5 hr the cellular pools of these amino acids became diminished and by 24 hr became markedly depleted. Chloroquine inhibited the uptake of 35S cystine by cystinotic cells during one hour incubations in phosphate buffered saline medium. Chloroquine altered the intracellular fate of exogenous 35S cystine into cystine, cysteine and glutathione (GSH) in cystinotic cells grown in both complete medium for 24 hr or placed in buffered saline for 2 hr. In the complete medium, chloroquine suppressed incorporation of label into cystine, cysteine and GSH pools after 1 hr. In the short-term study, the drug prevented the incorporation of label into cystine and cysteine pools after 45 min.

Amino Acids↗
PubMed1983

A tumor-associated lactic dehydrogenase virus suppresses the host resistance to infection with Listeria monocytogenes.

Infection of mice with lactic dehydrogenase virus (LDV) causes a lifelong chronic infection which is followed by alterations in immune responses during the acute phase of the infection. LDV was found to impair many functions of the reticuloendothelial system and to suppress macrophage-dependent immune responses. We tested the effect of acute infection with LDV in mice on the macrophage-mediated resistance to infection with a virulent bacterium. We found that LDV reduces the host's capacity to resist infection with Listeria monocytogenes. Many tumor lines which are transferred in mice are infected with LDV, and their growth rate is affected by the presence of the virus. It is therefore important to distinguish between immune alterations in tumor-bearing mice which are caused by the progressive growth of the tumor and those which are secondary to the viral infection. We tested whether LDV and a circulatory factor from tumor-bearing mice with similar suppressive effects on anti-Listeria immunity are two different entities or whether they are similar. We found that the factor is associated with LDV-infected tumor cells and is absent in LDV-free tumor cells. Other biological and physical characteristics supported the assumption that the tumor-associated factor is the LDV.

Animals↗
PubMed1983

Immunogenicity of the mutated H-2Kbm1 antigen(s). Test of thyroid graft rejection between B6.C-H-2bm1 and C57BL/6 mice following reciprocal immunization with normal versus malignant cells.

The immunogenic properties of one (or few) selected antigen(s) encoded by the mouse major histocompatibility complex was studied using the C57BL/6(B6) mouse strain and its descendant B6.C-H-2bm1(bm1) mutant. These strains differ in a point mutation in the H-2K region. We compared the immunogenic and antigenic expression of the mutated antigen on different bm1 tissues by testing the vulnerability of these tissues to graft rejection response in B6 recipients. Previous results demonstrated that B6 and bm1 mice do not reject reciprocal thyroid transplants, despite the acute rejection of reciprocal skin grafts. Thyroid grafts were rejected, however, after presensitizing the recipients with skin graft syngeneic with the thyroid, but not after sensitization with spleen cells. In the present work we induced tumors in bm1 mice by treating them with a chemical carcinogen (3-methylcholanthrene). We found that two out of four tumors demonstrated strict strain specificity and were rejected by all mouse strains (including the B6 recipients) except by their strain of origin. All tumors were found to be sensitive to in vitro lysis by B6 anti-bm1 effector cells. HZ1-A and HZ1-B tumor cells were rejected by B6 recipient mice but could not immunize B6 mice against a subsequent bm1 thyroid graft. When testing the immunogenicity of B6 originated EL4 leukemia cells (which are fatal to B6 mice), we found that the tumor cells were rejected by bm1 recipients, but, unlike B6 skin grafts, were incapable of inducing the rejection of a subsequent B6 thyroid transplant. The results demonstrated that an H-2K molecule may exhibit different immunological properties when expressed on cells of different tissues. The different expression of the mutated antigen on different cell types, its ability to trigger T cells but not B cells responses and the potential involvement of the tissue specific differentiation molecules in the graft rejection response are discussed.

Animals↗
PubMed1983

Effects of conceptual age and dietary intake on protein metabolism in premature infants.

Protein turnover was studied in eight premature infants of conceptual age 26-37 weeks. A stochastic model based upon [15N]urea or [15N]ammonia excretion following a single injection of [15N]glycine was used to estimate rates of whole body protein synthesis and catabolism. The urinary 3-methylhistidine/creatinine ratio was determined to differentiate skeletal muscle protein breakdown from total protein catabolism. The rates of whole body protein synthesis ranged from 5.2 to 13.2 g X kg-1 X day-1 and protein catabolism ranged from 4.1 to 12.4 g X kg-1 X day-1. Linear regression analyses of conceptual age versus (a) whole body nitrogen flux, (b) protein synthesis, and (c) protein catabolism showed significant inverse relationships. A similar relationship obtained between conceptual age and the urine 3-methylhistidine/creatinine ratio. Muscle protein breakdown did not vary with conceptual age, but the fraction of whole body protein breakdown derived from muscle protein breakdown increased significantly with advancing maturation. The ratio net tissue protein gain/total body protein synthesis increased significantly with increasing body weight. Net tissue protein gain appeared to be directly related to protein and caloric intake. The ratio of the rate of whole body protein synthesis and protein intake was greatest in the youngest infants and declined with maturation. A similar relationship was not found between the ratio of protein synthesis and caloric intake and the degree of maturity. More than 90% of nitrogen entering the metabolic pool was used for protein synthesis and more than 50% of calories administered were similarly utilized. We conclude that: (a) protein turnover in premature infants is far more rapid than in term infants, children, or adults and is inversely related to conceptual age; (b) muscle protein turnover constitutes a greater fraction of overall turnover with advancing maturity; (c) energy and protein intake affect net tissue protein gain significantly in rapidly growing infants; and (d) the efficiency of protein synthesis as a function of protein intake is higher in the most immature infants.

Body Weight↗
PubMed1983

Sex-associated differences in the immune response against fetal major histocompatibility antigens. II. Association of the female IgG1 with H-2K-encoded alloantigens.

Alloantibodies against the H-2b haplotype were produced in C3HeB female and male parental mice in response to transplantation of F1 fetal tissue (bones). In testing IgG1 and IgG2 antibodies by means of the FACS II we found striking sex-associated differences in the isotypes produced: female mice produced much more IgG1 than male mice, although they produced comparable amounts of IgG2. Using protein-A-sepharose-purified fractions of IgG1 and IgG2, raised in the parental females we found the specificity of this extra IgG1 to be directed against the H-2Kb private determinants, in contrast to the IgG2 which was found to be specific for H-2Kb, H-2Db and I-Ab subregion alloantigens. The relevance of the association between H-2K alloantigens and IgG1, in context of the fetal-maternal relationship is discussed.

Animals↗
PubMed1983

Uptake of L-[14C]proline by isolated rat brain capillaries.

Rat brain capillaries exhibit concentrative uptake of L-proline. The uptake is mediated by two saturable systems, one with a Km of 0.11 mM and another with a Km of 5.9 mM. Entry also occurred by diffusion, especially at high substrate concentrations. The saturable high-affinity system is sodium-dependent, with a Km for sodium of 36 mM. Proline uptake is not inhibited by lysine, but is inhibited by phenylalanine, glycine, and leucine. alpha-Methylaminoisobutyric acid (MeAIB), a model for sodium-requiring transport systems, is a competitive inhibitor of the low-Km system. b-2-Aminobicyclo-[2,2,1]-heptane-2-carboxylic acid (BCH), a model for nonsodium-dependent transport, however, also inhibited proline uptake.

Animals↗