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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 325 records · Page 18Linked to original sources
PubMed1985

Metastatic capacity of cloned T10 sarcoma cells that differ in H-2 expression: inverse relationship to their immunogenic potency.

Clones of the T10 sarcoma, originated in a (H-2b X H-2k)F1 mouse, differ in their metastatic competence, correlated with differences in the expression of antigens of the two parental haplotypes. In fact, the metastatic phenotype is determined by the H-2Dk antigen. Whether the different major histocompatibility complex gene products control the metastatic phenotype via their different immunogenic properties was tested. The involvement of the immune system in controlling the development of metastases was inferred from experiments in which nonmetastatic T10 cloned cells were found to produce both experimental and spontaneous metastases in syngeneic immune-suppressed mice. After the testing of T-cell-mediated immune responses, metastatic T10 cloned cells, which expressed the H-2Db and H-2Dk antigens, were nonimmunogenic in their syngeneic hosts, whereas nonmetastatic T10 cloned cells, which expressed predominantly the H-2Db antigens, evoked a strong T-cell response. H-2Db and H-2Dk antigens expressed on T10 cells appeared to differ in their immunogenicity. This was further supported by the observation that whereas a good antibody response was elicited by H-2Db antigens expressed on T10 cells, only a low anti-H-2Dk antibody was produced. The different T10 cloned cells were not susceptible to natural killer (NK) activity in an in vitro assay, yet in vivo studies suggested the participation of NK activity in controlling T10 metastasis. In animals with depressed NK activity, metastases were generated even by nonmetastatic clones, whereas in animals in which NK activity was elevated, even metastatic clones failed to generate metastases. Both T-cell-mediated immune responses, probably restricted by the H-2D products and NK reactivity, appeared to participate in controlling the development of metastases by T10 cells.

Animals↗
PubMed1985

Effect of radiation on the production of interleukins and T-lymphocyte activities.

The effect of 0-400 rad 60Co gamma-ray doses on distinct steps in the process of murine T-cell activation by concanavalin A (Con A) was investigated. When C57BL/6 spleen cells were stimulated immediately after irradiation, production of interleukin-1 (IL-1) and interleukin-2 (IL-2) was not impaired. Concomitantly, the display of IL-2 receptors in Con A-induced reactivity to IL-2 was not affected. The proliferative response was markedly diminished by increasing doses of radiation. The effect of radiation was found to depend not only on the delivered dose but also on the time interval between irradiation and stimulation of the lymphoid cultures. When the mitogenic stimulus was delayed for 24 hours following irradiation, IL-1 production was not diminished, whereas IL-2 production was impaired by doses greater than 200 rad. The proliferative response was diminished to a markedly higher degree as compared to the degree it was diminished in cell cultures stimulated by Con A immediately after irradiation. IL-2 production and the proliferative response to Con A of irradiated cell suspensions, cultured without mitogen for 24 hours post irradiation, were also assessed after adjustment for cell death. In this case, an impairment in IL-2 production that was dose dependent was apparent, but still the levels of IL-2 secreted by 400-rad irradiated cells reached high levels. In contrast, the proliferative response to Con A could not be restored. When T-cell growth factor was added concomitantly with Con A to irradiated cell cultures, a radioprotective effect could be observed.

Animals↗
PubMed1984

The differential expression of H-2K versus H-2D antigens, distinguishing high-metastatic from low-metastatic clones, is correlated with the immunogenic properties of the tumor cells.

Two clones of the 3LL Lewis lung carcinoma, a low-metastatic clone A9 and a high-metastatic clone D122, were studied for MHC expression and immunogenic properties. Using monoclonal antibodies, we demonstrated that the A9 clone expresses both the H-2Kb and the H-2Db, whereas the D122 expresses only the H-2Db, and lacks the expression of the H-2Kb encoded molecules. Cells of the low-metastatic clone A9 grew progressively in syngeneic (C57BL/6J) or in F1 mice, but were rejected in allogeneic recipients. The high-metastatic D122 grew progressively in all mouse strains tested, yet metastases were formed only in syngeneic recipients. When H-2 recombinant mice were used, the A9 again manifested a significantly greater immunogenic potency than the metastatic D122, which grew in all 4 recombinants tested. Metastases, however, were formed in B10HTG and to a lesser extent in B10A(4R), thus indicating that metastasis formation is restricted by both C57BL background and H-2Db sub region. We subsequently tested whether the higher immunogenicity of the H-2Kb-positive A9 cells is expressed also in syngeneic mice, to examine whether this could account for its low metastatic phenotype. We found that immunization by A9 cells significantly inhibited the growth of a subsequent A9 graft and even of D122, yet D122 did not retard the growth of secondary D122 or A9 cells. The increased immunogenic effect was expressed also in the generation of syngeneic cytotoxic lymphocytes by A9 but not by D122 cells. We suggest that expression of H-2K molecules on the 3LL clones, immunogenicity and the metastatic phenotype are causally related in this system.

Animals↗
PubMed1984

Inositol uptake by cultured isolated rat Schwann cells.

The uptake of radiolabeled myo-inositol by Schwann cells isolated from the sciatic nerve of 2-4 day old rats was found to occur by a saturable, sodium-dependent phlorizin-inhibited mechanism with an estimated Km of 30 microM. The system was inhibited by galactose and glucose but not by galactitol. At high concentrations of myo-inositol, a diffusion-like process appeared to be functional. The characteristics of the saturable system are very similar to those of myo-inositol uptake by the endoneural fascicle preparation of sciatic nerve.

Animals↗
PubMed1984

Immuno-selection in vivo of H-2D phenotypic variants from a metastatic clone of sarcoma cells results in cell lines of altered metastatic competence.

To find out whether manipulation of H-2 expression on metastatic cells could alter their metastatic properties, we immunoselected in vivo H-2 antigen variants from a metastatic clone of the T10 sarcoma [originating in a (C57BL/6J X C3H.eB)FI mouse] and tested their metastatic capacity. The unselected metastatic cells (IE7) were previously found to express H-2Db and H-2Dk antigens, but they did not express the H-2K antigens of either parental haplotype. Transplantation of IE7 cells into C57BL/6J irradiated mice resulted in loss of H-2Dk expression and a reduction in H-2Db antigen density. Further transplantation of these cells into non-irradiated C57BL/6J mice led to a total loss of H-2 expression. The cells concomitantly lost their metastatic potency. Immunoselection of IE7 cells in C3H.eB irradiated and non-irradiated mice resulted in cells which were H-2Dk-positive but H-2Db-negative. Cells of these selected variants not only retained their metastatic potential, but in fact were far more metastatic than the unselected IE7 cells. Thus, changes in H-2 expression on tumor cells may alter their metastatic potential. In the case of T10 cells, H-2Dk expression seems to be directly involved in their metastatic capacity.

Animals↗
PubMed1984

Receptor-mediated endocytosis of tuftsin by macrophage cells.

A fluorescent analog of the phagocytosis stimulating peptide tuftsin was prepared by coupling tetramethyl rhodamine isothiocyanate to a C-terminal elongated derivative of tuftsin. This analog, Thr-Lys-Pro-Arg-Gly-Lys(N epsilon-tetramethyl rhodamine)-OH, was used to visualize tuftsin receptors on mice macrophage cells by fluorescent image intensification. Fluorescent labelling was carried out at 37 degrees C, using a concentration of 200 nM and 2 microM of the fluorescent tuftsin derivative. The formation of peptide-receptor clusters and their subsequent internalization, as discerned by image intensification, were rapid processes, 5 min and 5-30 min, respectively. Preincubation of macrophages with tuftsin for various time intervals, followed by quantification of the tuftsin receptor using radiolabelled tuftsin, suggest that tuftsin receptors are initially increased in amount (5-7 min) and subsequently reduced (after 10-15 min) as judged by sites available for tritiated tuftsin. The binding studies are rather complementary to the fluorescence observations and support the assumption that the tuftsin receptor on the membrane of the mice macrophage cell is rapidly mobilized.

Animals↗
PubMed1984

Accumulation of galactonate in liver of suckling rats perfused with galactose.

Livers of 14-day-old suckling rats were perfused for 30 min in the nonrecirculating (once-through) mode with media containing 0-60 mM galactose. Galactonate was detected in livers perfused with as little as 1 mM galactose and increased with higher perfusate galactose to 178 nmoles per gram of liver at 60 mM hexose. Tissue galactonate levels were as high as 60% of galactose-1-phosphate which also accumulated under the same conditions. Galactonate was also found to be present in the effluent perfusate. The perfused suckling rat liver appears to be a physiological model for assessing the role of galactose oxidation to galactonate as an alternate metabolic pathway of galactose metabolism.

Animals↗
PubMed1984

Nonmetastatic tumor cells acquire metastatic properties following somatic hybridization with normal cells.

Somatic cell hybridization between nonmetastatic tumor cells and normal cells of the lymphoreticular system results in hybrid cells manifesting metastatic properties of defined target organ specificity. Thus, fusion of the nonmetastatic BALB/c originated NSI plasmacytoma with C57BL B lymphocytes resulted in hybridomas, each of which were metastatic. Of 10 hybridomas, 7 generated metastases in the spleen and liver, whereas 3 generated liver metastases. The generation of liver metastases by hybridomas which homed to both spleen and liver, but not by those which homed to the liver only, was controlled by the spleen. The acquisition of metastatic properties via somatic cell fusion seems to represent a general principle, in which the normal partner determines the target organ specificity for the metastatic growth. Thus, fusion of SP2/O myeloma cells with syngeneic B lymphocytes also resulted in a hybrid cell metastasizing to the spleen and liver, yet a somatic hybrid between NSI and a macrophage or dendritic-like cell metastasized to the lung. Cell surface molecules encoded by the genome of the normal partner was demonstrated to control the target organ specificity: antibodies against MHC-encoded antigens of the normal B cell partner prevented the generation of metastases by hybridomas metastasizing to the spleen and liver, but not by those metastasizing to the liver only. This is in accordance with the function of MHC molecules on lymphocytes in controlling their homing to lymphoid organs. Hybridomas of T cell lymphomas also manifested metastatic properties. Analysis of the cell surface Thy-1 antigens of a hybridoma (DCH10), produced via somatic fusion between BW5145 lymphoma and a putative macrophage cell indicated that cells of liver metastases (DCH10-Li) generated by the hybrid cells might have undergone further somatic cell fusion in vivo with host (T?) cells. These cells have acquired new metastatic properties, generating metastases in spleen, liver and kidneys. In fact, even the inoculation of the parental BW lymphoma cells resulted in a case of liver metastasis (BW-Li). Such BW-Li cells, upon reinoculation, also generated metastases in the spleen, liver and kidneys. Analysis of the Thyl phenotype indicated that BW-Li cells may also have undergone somatic cell fusion in vivo with host (T?) cells, resulting in the acquisition of metastatic properties. The pattern of cell-cell interactions (adhesion, infiltration) with liver cell monolayers of BW-Li cells and of DCH10-Li (T-cell lymphomas) was identical, and differed from cells of liver metastases of the myeloma-B cell hybridomas which might be based on responses to liver growth signals.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Absence of a role of gamma-glutamyl transpeptidase in the transport of amino acids by rat renal brushborder membrane vesicles.

The role of the enzyme, gamma-glutamyl transpeptidase on the uptake of amino acids by the brushborder membrane of the rat proximal tubule was examined by inhibiting it with AT-125 (L-[alpha S, 5S]-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid). AT-125 inhibited 98% of the activity of gamma-glutamyl transpeptidase when incubated for 20 min at 37 degrees C with rat brushborder membrane vesicles. AT-125 given to rats in vivo inhibited 90% of the activity of gamma-glutamyl transpeptidase in subsequently isolated brushborder membrane vesicles from these animals. AT-125 inhibition of gamma-glutamyl transpeptidase both in vivo and in vitro had no effect on the brushborder membrane uptake of cystine. Similarly, there was no effect of gamma-glutamyl transpeptidase inhibition by AT-125 on glutamine, proline, glycine, methionine, leucine or lysine uptake by brushborder membrane vesicles. Furthermore, the uptake of cystine by isolated rat renal cortical tubule fragments, in which the complete gamma-glutamyl cycle is present, was unaffected by AT-125 inhibition of gamma-glutamyl transpeptidase. Therefore, in the two model systems studied, gamma-glutamyl transpeptidase did not appear to play a role in the transport of amino acids by the renal brushborder membrane.

Amino Acids↗
PubMed1984

Factors regulating the specific activity of galactose-1-phosphate uridyltransferase during perfusion of suckling rat liver.

The regulation of the specific activity of galactose-1-phosphate uridyltransferase (E.C.2.7.7.12) has been studied using the hexose-perfused suckling rat liver as a model. Perfusion in the recirculating mode with galactose concentrations up to 4mM resulted in enzyme activity which fluctuated significantly during a 90-min experimental period. A concentration of 10 mM galactose stabilized the enzyme activity at levels found in unperfused liver. The same stabilizing effect was seen with 10 mM glucose. The elevated transferase specific activity observed after 30 min recirculating perfusion was not seen when the nonrecirculation mode was employed suggesting a factor in the recirculating medium may mediate this effect.

Animal Population Groups↗
PubMed1984

Urinary excretion of dimethylarginines in premature infants.

Urinary excretion of NG,N'G-dimethylarginine (NG,N'G-Me2Arg) and NG,NG-dimethylarginine (NG,NG-Me2Arg) was measured in premature infants. The NG,N'G-Me2Arg/NG,NG-Me2Arg ratio was much higher in newborn infants than in older children or adults. Linear regression analysis showed a significant negative correlation between the degree of maturity and the excretion of NG,N'G-Me2Arg. A significant direct linear relationship also was found between the excretion of NG,N'G-Me2Arg and the rate of whole body nitrogen flux and of protein synthesis and catabolism. No correlation was found between the excretion of the dimethylarginines and 3-methylhistidine, but the dimethylarginine/3-methylhistidine ratio declined with advancing conceptual age. A direct linear relationship was found between excretion of NG,N'G-Me2Arg and NG,NG-Me2Arg and whole body nonskeletal muscle protein breakdown. No correlation was found between nonskeletal muscle protein catabolism and 3-methylhistidine excretion. We estimate that approximately 0.34 mumole of dimethylarginine are excreted per gram of nonskeletal muscle protein catabolized. Dietary intake did not affect the excretion of either NG,N'G-Me2Arg or NG,NG-Me2Arg. The data suggest that measurement of urinary dimethylarginines might be useful in the nutritional assessment of premature infants.

Adolescent↗
PubMed1984

Renal tubule reabsorption of amino acids after lysine loading of cystinuric dogs.

The renal reabsorption of cystine, lysine, arginine, and ornithine as well as other amino acids has been determined before and after lysine infusion in four normal and five cystinuric dogs. The large filtered load of lysine caused defective reabsorption of cystine in three of four normals and augmented the basal defect in all of the cystinuric dogs. Two of the cystinuric dogs responded with cystine clearances in excess of the glomerular filtration rate. The magnitude of increase of the reabsorptive defect for cystine observed after lysine infusion into the cystinuric dogs was unrelated to the extent of the basal defect. Two of the normal dogs and four of the five cystinuric dogs demonstrated defective arginine reabsorption after lysine loading, one of the cystinuric dogs having greater arginine excretion than the filtered load. Although normal dogs showed a moderate inability to reabsorb the large filtered load of lysine, three of the cystinuric dogs exhibited a -60 to -70% reabsorption, consistent with lysine secretion. Both normal and cystinuric dogs showed defective glycine absorption after lysine loading, but only cystinuric dogs showed variable defects in threonine, serine, histidine, methionine, and tyrosine when the basic amino acid was infused. Each cystinuric dog responded to lysine infusion in a different way, and the overall pattern of response differed from the normal, with evidence of induced secretion of cystine, lysine, and arginine in the affected dogs.

Absorption↗
PubMed1984

Enhanced galactose metabolism in isolated perfused livers of folate-treated suckling rats.

Folic acid (1 mg/day) was administered intraperitoneally to seven-day-old suckling rats for a period of seven days. Livers of folate-treated animals took up galactose rapidly during the first 35 minutes of perfusion, whereas uptake was delayed in the controls (sham-injected and untreated). More glucose was released by all groups when galactose was perfused than when other substrates were used. With each hexose tested, livers of the folate group consistently released less glucose but more lactate than the controls. The specific activity of galactose-1-phosphate uridyltransferase was elevated in livers of the folate group compared to the controls perfused with either galactose or glucose. A similar finding was made for ATP levels in perfused livers of this group. The differences in transferase and ATP levels in perfused livers of folate-treated over the control groups may explain the enhanced galactose uptake pattern.

Adenosine Triphosphate↗
PubMed1984

Specific activity of carp antisera against beta 2-microglobulin (beta 2m) and evidence for a beta 2m homologue in carp (Cyprinus carpio).

Antisera against rabbit and human beta 2-microglobulin were produced in carp (Cyprinus carpio). These antisera were found to be specific for beta 2m, and detected beta 2m epitopes in various vertebrates including guinea-pig, cow, mouse, rat, dog, horse, cat, sheep, goat, parrot, chicken and frog. In addition, these antisera were also inhibited by an extract from oyster. The differences between the reactivity of these two antisera and the ability of the anti-rabbit beta 2m to distinguish between mouse and rat beta 2m's suggested that the carp itself carries beta 2m epitopes. This hypothesis was corroborated by the ability of a variety of mammalian anti-beta 2m antisera to induce a mitogenic response in carp leukocytes. Finally, a rabbit antiserum against dog beta 2m was shown to precipitate a low molecular weight molecule from carp leukocyte extract. This molecule is likely to represent the carp homologue of mammalian beta 2m.

Animals↗
PubMed1984

Whole body nitrogen kinetics in man: determination from plasma [guanidino-15N]arginine.

Whole body nitrogen turnover and protein synthesis were calculated by the method of D. Picou & T. Taylor-Roberts [Clinical Science and Molecular Medicine (1969) 36, 283-296] except that plateau plasma enrichment of [guanidino-15N]arginine was used in place of the [15N]urea enrichment after a constant infusion of [15N]-glycine. With this approach metabolic pool turnover and protein synthesis were 637.2 +/- 73.0 mg of N day-1 kg-1 and 2964.0 +/- 409.5 mg of protein day-1 kg-1 respectively. Virtually identical isotopic enrichment in [guanidino-15N]arginine and [15N]urea were observed in a healthy young adult who took repeated oral doses of [15N]glycine for a period of 60 h: 0.47 (arginine) and 0.48 (urea) atom% excess. The turnover of glycine nitrogen and of urea, determined from the constant infusion of [15N]glycine and [13C]urea, was 66.2 +/- 3.3 mg of N day-1 kg-1 and 156.2 +/- 4.3 mg of urea day-1 kg-1 respectively. The ratio of steady-state enrichment in arginine to that in glycine, reflecting the fraction of arginine derived from glycine, was 10.5%. By using the [guanidino-15N]arginine enrichment as representative of the expected enrichment in [15N]urea at plateau, it was calculated that approximately 25% of glycine N flux is directed toward the synthesis of urea, with the remainder directed to protein and quantitatively minor products like haem and creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Growth characteristics of human first trimester decidual cells cultured in serum-free medium: production of prolactin, prostaglandins and fibronectin.

A procedure for the establishment of pure human first trimester decidual cells in primary cultures has been developed. The high rate of success in obtaining such cultures resulted from the elimination of fibroblasts by appropriate enzyme dissociation and filtration of the initial tissue sample, and subsequent maintenance of the cells in a serum-free medium supplemented with insulin, fibroblast growth factor (FGF), estradiol, progesterone, hydrocortisone, transferrin and sodium selenite. Under these culture conditions, we obtained pure and actively dividing decidual cells forming tightly packed and nonoverlapping epithelioid cell monolayers covering more than 75% of the culture area. The cultured decidual cells retained their in vivo capacity to produce prolactin and various prostaglandins (PGs), primarily PGE2. There was a marked reduction in hormone production after 20 days in culture. A massive network of fibrillar surface fibronectin was detected by indirect immunofluorescence staining of the cultured cells. The production of prolactin and PGs together with the secretion of fibronectin may play a role in the implantation and subsequent growth of the embryo. The described procedure of obtaining fibroblast-free decidual cell monolayers will promote studies on the hormonal regulation of this tissue at the time of early intrauterine life.

Cells, Cultured↗
PubMed1984

Metabolism of 15NH3 in organotypic cerebellar explants and cultured astrocytes: studies with gas chromatography-mass spectrometry.

Gas chromatography-mass spectrometry was used to study the metabolism of 15NH3 in organotypic cerebellar explants and cultured astrocyte monolayers. A steady-state level of 15NH3 was present by 1 min in both systems. Steady-state labeling in L-[amide-15N] glutamine, L-[15N]alanine, L-[15N]glutamate, and L-[15N]aspartate was attained by 1 min after 15NH3 addition in the organotypic cerebellar explants and by approximately 5 min in the cultured astrocytes. No measurable 15N labeling was noted in either glycine or serine in either system.

Ammonia↗