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Biomedical subjects

S Segal

Publications and source records attributed to S Segal.

At least 505 records · Page 28Linked to original sources
PubMed1979

Late-onset nonketotic hyperglycinemia and spinocerebellar degeneration.

Investigation of a 15-year old boy with progressive optic atrophy and spinocerebellar degeneration revealed elevated plasma, cerebrospinal fluid, and urine glycine concentrations. During an oral glycine loading test, the patient's plasma glycine concentration rose to a higher level than control values, although the initial rate of rise was slower; there was no concomitant rise in the plasma serine concentration. An oral serine loading test resulted in a prompt rise of both glycine and serine serum concentrations. The renal glycine clearance was elevated, and the renal tubular glycine reabsorption was diminished. These findings of decreased intestinal uptake and increased renal tubular glycine clearance suggest that a generalized derangement of glycine entry into cells may account for the phenotypic manifestations of the disorder.

Adolescent↗
PubMed1979

Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells.

Infection of differentiated mouse embryo cells by simian virus 40 (SV40) leads to the production of the early mRNAs and the tumor (T) antigens that they encode. In contrast, undifferentiated F-9 murine teratocarcinoma cells do not support these early stages of the SV40 cycle. This block results from the inability to accumulate stable processed early SV40 mRNAs. It has recently been shown that vitamin A and its derivatives can induce in vitro differentiation of stem cells. Undifferentiated F-9 cells, upon treatment with a low concentration of retinoic acid, exhibited pronounced morphologic changes as well as the appearance of the H-2 surface antigens. After differentiation, the susceptibility of F9 cells to SV40 infection could be demonstrated by the appearance of large T and small T antigens, as shown by immunofluorescence and immunoprecipitation. Furthermore, SI nuclease mapping of early SV40 transcripts confirmed the presence of the two spliced early mRNAs. These results indicate that the undifferentiated F-9 stem cells contain the genetic information needed for generating stable processed early SV40 mRNAs but are blocked in the production of functional species.

Animals↗
PubMed1979

Immunological tolerance: high-dose antigen-induced suppressor cells from tolerant animals inactivate antigen-presenting macrophages.

Studies were carried out to characterize the target cell for the activity of suppressor cells induced in highzone tolerance to deaggregated human gamma globulin (HGG). We applied an in vitro system for the initiation of an immune response, consisting of culturing spleen lymphocytes on HGG-fed macrophages, in which initiator T cells are generated. These cells, when injected into the foot pads of syngeneic mice, recruit specific anti-HGG effector T lymphocytes. We found that HGG-fed macrophages were incapable of signaling spleen cells from HGG-tolerant animals to generate initiator cells. Spleen cells from tolerant animals, when mixed with spleen cells from normal donors, inhibited the capacity of the normal population to give rise to initiator cells after culture on HGG-fed macrophages. Thus, suppressor T cells, which inhibit education of T cells by antigen-fed macrophages, exist in the tolerant spleen. Spleen cells from HGG-tolerant animals, when seeded on macrophages fed simultaneously with HGG and keyhole limpet hemocyanin (KLH), also prevented the macrophages from signaling an anti-KLH response. Spleen cells from HGG-tolerant animals from which the suppressor cells were depleted by "affinity chromatography" on histamine columns, when seeded on macrophages fed with HGG and KLH, generated initiators to both antigens. It appears, therefore, that suppressor cells act at the level of antigen-presenting macrophages, affecting macrophages fed with the tolerogen, and therefore affecting also the immunogenic effect of other antigens presented by the same macrophages. By testing the mode of action of suppressor cells on the tolerogen-fed macrophage, we found that the suppressors manifest a cytotoxic effect on such macrophages. We propose that the suppressor cell is, in fact, an anti modified-self killer, acting on macrophages possessing surface self-antigens "modified" by the tolerogen. The similarity in cell-surface markers between suppressors and anti modified-self killers supports this concept.

Animals↗
PubMed1979

Thymus-derived lymphocytes control the expression of immunogenic properties of peritoneal macrophages.

Macrophages, given keyhole limpet hemocyanin in vitro, from normal mice initiate in culture antigen-specific T cell-mediated immune reactions. On the other hand, macrophages from nude, from adult-thymectomized, or from neonatal-thymectomized mice are impaired with respect to their capacity to signal such an antigen-specific T cell reaction. Thymocytes from hydrocortisone-treated donors, added in culture to such impaired macrophages, rendered them immunologically potent. The capacity of macrophages from adult thymectomized mice to promote the activation of antigen-specific "helper" T cells which, cooperating with B lymphocytes, would lead to antibody production, was also impaired. Thus, it appears that short-lived T lymphocytes control the maturation of macrophages up to a stage at which they can present antigen-specific T cells with antigen in an immunogenic form. We found that such T lymphocytes also control the phagocytic properties of macrophages, yet the impairment of their immunogenic properties does not seem to be derived from decreased phagocytosis.

Animals↗
PubMed1979

On the clinical significance of the plasma alpha-amino-n-butyric acid:leucine ratio.

The ratio of plasma alpha-aminobutyric acid to plasma leucine that has been proposed as a specific biochemical marker of alcoholic liver injury, was measured in normal children an children with a variety of metablic disorders. The ratio was found to be lower in children that in adults. It was elevated in children with Reye's syndrome, tyrosinemia, homocystinuria, nonketotic hyperglycinemia, and ornithine transcarbamylase deficiency. The results indicate that an elevated ratio is not specific for adults with alcoholic liver injury and that the ratio may be high even without the presence of clinically apparent hepatic disease. An altered ratio may reflect the presence of an inherent metabolic defect.

Adult↗
PubMed1979

Differences in cell surface antigens of tumor metastases and those of the local tumor.

Tests were made to determine whether cell surface tumor antigens of metastases differed from the tumor antigens of the cell population of the local tumor growth. C57BL/6 mouse spleen lymphocytes sensitized against monolayers of the local growth of the 3LL Lewis lung carcinoma (L-3LL) in the presence of syngeneic serum generated lymphocytes that were cytotoxic to L-3LL but significantly less cytotoxic to target cells derived from lung metastases (M-3LL). Lymphocytes sensitized against M-3LL were significantly more cytotoxic against M-3LL than against L-3LL cells. Anti-M-3LL cytotoxic lymphocytes but not anti-L-3LL, admixed with either L-3LL cells or M-3LL tumor cells, when injected into syngeneic recipients reduced lung metastasis significantly. Results indicated that cells with high metastatic capacity and distinct antigenic properties exist within the tumor cell population and that immunoselection might be involved in the production of lung metastases.

Animals↗
PubMed1979

Fetal bone grafts do not elicit allograft rejection because of protecting anti-Ia alloantibodies. Implications to the immune survival of fetuses in allogeneic mothers.

In a previous study we showed that allografts of BN fetal bone, unlike allografts of adult bone, are not rejected by allogeneic recipients of the Lewis strain in spite of the existence of major histocompatibility complex (MHC) incompatibility between donors and hosts. In the present study, we analyzed the relationships existing between the host and fetal tissue that determine graft survival. We found that (1) the fetal BN graft, unlike adult grafts, induces in Lewis recipients a vigorous humoral response consisting mainly in the production of IgG antibody that seems to be directed against antigens of Ia-like specificities. (2) The BN rats are genetically defective in their capacity to respond to determinants and thus are not capable of producing anti-Ia antibodies; in accordance, Lewis fetal bone grafts are rejected by the BN recipients. (3) Chondrocytes isolated from fetal mouse bones do express Ia antigenic determinants. We suggest that the survival of an allogeneic fetal graft in an immunologically intact recipient depends on an active and selective immune response directed against the Ia components associated with the MHC on the embryonic and fetal cells. On the basis of these notions, we propose that the capacity of Ia determinants expressed on cells of the embryo, to elicit anti-Ia and IgG alloantibodies in the pregnant mother, determines the capacity of the embryo to escape rejection by the histoincompatible mother.

Animals↗
PubMed1979

Galactose metabolism in isolated perfused suckling-rat liver.

The metabolic conversion of 1, 2, or 4 mM galactose to glucose was studied in isolated livers of suckling rats. Whereas galactose uptake during perfusion with 1 and 2 mM galactose was linear throughout the 90-min experiment, uptake was delayed for 35 min when 4 mM galactose was perfused. Studies with radioactive galactose revealed a parallel disappearance of galactose and the appearance of [14C]glucose; about 80% of the galactose taken up was converted to glucose. Galactose perfusion appeared to reduce the basal amount of glucose derived from substrates other than galactose. The specific activities in the galactose-perfused livers of the three major galactose metabolizing enzymes, galactokinase, galactose-1-phosphate uridylyltransferase, and uridine diphosphogalactose-4-epimerase, revealed that the transferase was significantly lower, whereas that of galactokinase and epimerase were significantly higher than in livers perfused without galactose. No meaningful changes were observed in the levels of either phosphorylated or uridylated hexoses in these studies.

Animal Population Groups↗
PubMed1979

Amino acid content of rat renal cortex and the response to in vitro incubation.

The concentration of aspartic acid, threonine, serine, glycine, and alanine is significantly higher in newborn rat renal cortex than in the adult tissue, while phenylalanine and histidine are higher in the adult. When adult cortical slices are placed in bicarbonate buffer at room temperature for 20 min there is a 30-60% decrease in the levels of all amino acids except for lysine, which is slightly higher, and methionine and serine, which do not change. Under the same conditions, newborn cortical slices reveal a similar decrease in only glycine, tyrosine, histidine, and the branched-chain amino acids. On subsequent in vitro incubation of the cortical slices at 37 degrees C for 120 min the concentrations in adult tissue remain at the lower values observed on removal from buffer at room temperature except that glutamic acid, glycine, and lysine levels decrease further and serine increases to the concentration found in fresh tissue. Newborn tissue when incubated at 37 degrees C for 120 min shows amino acid concentrations comparable to unincubated fresh tissue for all except aspartic acid, glutamic acid, serine, and phenylalanine, which reach levels higher than unincubated tissue. The ability of newborn tissue to maintain amino acid pools may play a role in the enhanced transport of some amino acids resulting from preincubation at 37 degrees C (Reynolds et al. Science 184: 68-69, 1974; Reynolds and Segal, Biochim. Biophys. Acta 406: 513-525, 1976).

Aging↗
PubMed1979

Hypoxanthine uptake in isolated rat renal cortical tubule fragments.

Isolated renal tubule fragments prepared from adult Sprague-Dawley rats were used to study the cellular uptake of hypoxanthine. This uptake was rapid, reaching a steady state after 30 min of incubation. Analysis of the intracellular pool during the initial uptake and at the steady state revealed a concentration gradient of hypoxanthine consistent with active transport, although only one-third of the transported hypoxanthine remained unmetabolized. The remainder of the transported hypoxanthine was converted to inosine and inosinic acid, but detectable conversion to uric acid was not noted. A kinetic analysis of uptake revealed that two systems for cellular entry of hypoxanthine existed with K(m1) = 0.005 and K(m2) = 0.80 mM. Hypoxanthine uptake at physiologic concentrations was oxygen, sodium, and temperature dependent, but the addition of metabolic fuels and alteration of the medium pH over the range of from 6.1 to 7.4 had no effect. Adenine, guanine, and inosine inhibited the uptake of hypoxanthine via the low-K(m) system which mediates the majority of uptake at physiologic levels. Xanthine, uric acid, and probenecid inhibited uptake via the high-K(m) system, but did not affect uptake via the low-K(m) system. The data indicate that hypoxanthine at physiologic levels is transported into the renal tubule cell via a system different from that for other oxypurines.

Adenine↗
PubMed1979

Size of rat spermatozoa during maturation along the epididymis.

An electrical sizing apparatus based on the Coulter Counter was used to measure rat spermatozoa from the proximal (caput) and distal (caudal) ends of the epididymis and from the ejaculate. The typical size distribution is unimodal with a positive skew, the crescent shape of the cells precluding absolute volume determination. During their passage through the epididymis, spermatozoa decrease in size as part of maturation. Saponin causes cell lysis and chymotrypsin cell shrinkage, both effects being more pronounced in the proximal region. It would seem that, during the maturation process within the epididymis, changes occur in the spermatozoon membrane that make the cells more stable.

Animals↗
PubMed1979

Segregation of human peripheral blood lymphocytes according to their affinity for insolubilized histamine. Principal differences between males and females.

An attempt was made to investigate the possible existence of differences in the composition of peripheral blood lymphocytes between males and females. Using affinity chromatography of human peripheral mononuclear cells on insolubilized histamine together with staining by fluoresceinated histamine-rabbit serum albumin (HRSA) we revealed that males possess a significantly higher proportion of mononuclear cells which bind to HRSA. These results are also reflected in sex-related differences in proliferative responses of the HRSA-non-adherent mononuclear cell population to T cell-dependent mitogens antigens and allogeneic mononuclear cells.

Animals↗
PubMed1979

Differences in resistance of metastatic tumor cells and cells from local tumor growth to cytotoxicity of natural killer cells.

Cells from local tumor growth (L-3LL) were compared to metastatic tumor cells (M-3LL) for their susceptibility to the cytotoxicity of natural killer (NK) cells. M-3LL cells were more resistant in vitro to NK cells from normal spleens than were L-3LL cells. A similar phenomenon of relative resistance of metastatic cells to NK activity was found when L-3LL and M-3LL cells were admixed with normal spleen cells and then inoculated into syngeneic mice. Because hybrid resistance was shown to be based on mechanisms that in principle are similar to mechanisms involved in NK activity, we tested the growth of M-3LL and L-3LL cells in semiallogeneic F1 mice. The in vitro effect of NK cells from semiallogeneic mice on M-3LL and L-3LL cells was tested in parallel. In vitro tests showed that irrespective of the haplotype of the spleen cell donors, L-3LL cells were more susceptible to NK activity than were M-3LL cells. In vivo experiments indicated that whereas M-3LL and L-3LL cells grew similarly in syngeneic recipients, M-3LL cells grew far more in F1 mice than did L-3LL cells. Thus metastatic cells are more resistant to NK activity than are cells of the local tumor growth. This relative resistance may determine, among other factors, the metastatic spread and progression of tumor cells.

Animals↗