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S Segal

Publications and source records attributed to S Segal.

At least 253 records · Page 14Linked to original sources
PubMed1989

Holocarboxylase synthetase deficiency: 9-year follow-up of a patient on chronic biotin therapy and a review of the literature.

We report on the long-term medical and neurodevelopmental follow-up of a patient with the rare and potentially lethal disease, holocarboxylase synthetase deficiency. He was originally treated prenatally with biotin megatherapy and for 9 years with 6 mg/day since his only episode of fulminant acidosis at 3 months of age. While growth and general health have been normal, the patient has exhibited signs of minimal brain dysfunction. However, evaluation of unaffected siblings suggests that this may be unrelated to his metabolic disease. A review of the literature and recommendations for optimal treatment are provided.

Biotin↗
PubMed1989

Galactose as a regulatory factor of its own metabolism by rat liver.

As part of a series of studies to assess the regulation of hepatic galactose-metabolizing enzymes, galactokinase, galactose-1-phosphate uridyltransferase, and UDPgalactose-4-epimerase, the effect of feeding a high galactose-containing diet to normal adult and pregnant female rats was examined. Sixteen days of galactose exposure of adult virgin females produced a different response in the specific activity of each of the enzymes, that of galactokinase being lower, transferase higher, and epimerase transiently elevated. Galactose feeding increased the specific activity of transferase in pregnant rat liver above the elevated level that already exists in the pregnant state but failed to influence the enzyme of the developing fetal liver. Galactose added to liver homogenates did not activate transferase. The increased activity in liver of adult, fed animals was not associated with a change in isoenzyme patterns examined by isoelectric gel electrophoresis but was characterized on kinetic analysis by an increase in Vmax for UDPglucose. The changes in enzyme specific activity in liver of animals fed galactose appear to have physiologic significance because hepatocytes isolated from galactose exposed livers take up more galactose and convert more to glucose and lactate than cells from control animals.

Animals↗
PubMed1989

Cystinuria in dogs: comparison of the cystinuric component of the Fanconi syndrome in basenji dogs to isolated cystinuria.

Two animal models for cystinuria have been examined: the Basenji dog with Fanconi syndrome and cystine stone-forming dogs of various breeds. Brush-border membranes were isolated from these animals and uptake of D-glucose and L-cystine was characterized. Experiments with isolated brush-border vesicles from Basenji dogs with cystinuria as a component of the Fanconi syndrome showed diminished sodium-dependent D-glucose uptake but no decrease in L-cystine uptake even though the cystine defect in vivo was as high as 94% (ie, 6% reabsorption). In contrast, brush-border vesicles isolated from the kidney of a cystine stone-forming dog (Welsh Corgi) with a cystine defect of only 16% (ie, 84% reabsorption) had decreased uptake of cystine compared to values found for Beagle and Basenji vesicles. Thus, cystinuria found in Basenji dogs with the Fanconi syndrome differs from that in classic stone-forming cystinuric dogs. The alteration responsible for the cystinuria of Basenji dogs with Fanconi syndrome does not appear to have a membrane locus and may reflect altered energetics for transport, which are not detected in isolated vesicles. The cystine defect in cystinuric stone-forming dogs does appear to be reflected in the isolated membrane.

Amino Acids↗
PubMed1989

Prospective study of the pituitary-ovarian function after tubal sterilization by the Pomeroy or Uchida techniques.

Surgical sterilization has become one of the most widely used methods of fertility regulation in the world. A common concern is the not yet clarified possible disturbance of the ovarian function resulting from the surgical procedure. A prospective study was carried out to contribute toward answering this question. Twenty subjects were enrolled in a longitudinal study of ovarian endocrine function before, and 2 and 6 months after, tubal ligation. The Pomeroy technique, which may compromise ovarian circulation, and the Uchida technique, which is free of this risk, were used randomly. Eight women who underwent to the Pomeroy technique and 9 who underwent the Uchida technique completed the protocol. Luteinizing hormone, follicle-stimulating hormone, estradiol, and progesterone were measured daily from days 10 through 18 of the cycle and every other day until the onset of the next menses. No change in any of the hormones studied was observed, with the exception of a significant increase in progesterone 2 months after tubal ligation by the Uchida technique.

Female↗
PubMed1989

The relationship between MHC antigen expression and metastasis.

From the studies summarized here a complex picture of the role played by MHC products in determining tumorigenicity and metastasis is emerging. In order to be able to understand this relationship better, it is necessary to consider several factors. 1. Each tumor system or neoplastic tissue is unique, and its behavior reflects the influence of cell-specific characteristics, as well as its ability to modulate other cells and tissues--including cells belonging to the immune system--and also to be modulated by other cells and soluble factors. 2. Since metastasis formation is a multistep process in which only small subpopulations of tumor cells with complex and defined phenotypes are able to colonize secondary tissues, elimination of even one single phenotypic component of this structured process can easily reverse the metastatic capacity of the cells. Acquisition of metastatic ability, on the other hand, would be a more difficult task, since any new characteristic expressed by the cells or induced experimentally, such as gene transfection or results of IFN treatment, must be expressed in a temporal manner and in concert with other cellular characteristics. Therefore, an experimental protocol measuring a specific element in determining metastasis can easily produce conflicting results, depending on the type of cells and genetic background of the host studied. 3. The level of specific MHC products on tumor cells is one among many other cell characteristics that may determine the metastatic potential of cells. Moreover, each of the class 1 MHC products, and the relationship among them, including other than the classical K, L, or D products (Brickell et al., 1983), should be regarded as independent entities, with possible different regulatory roles in cell-cell recognition, in a general sense, which may be involved in determining invasiveness and homing as well as recognition by the immune system. 4. Both specific T-cell and nonspecific natural mediated immunity (which is much less understood) are involved in the selection of the metastatic cell population. 5. Immunogenicity of tumors is not necessarily determined by high levels of MHC antigen expression; it is also dependent on the level of TSA. Thus, immunoselection mediated by T lymphocytes during metastasis formation could be directed against both MHC and TSA antigens. Therefore, low expression of MHC antigens by metastatic cells as a result of immunoselection is not always observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

The dialectical approach in group therapy.

A dialectical therapeutic approach has been used in treating individuals and families. Its application in group therapy is described with the aid of several anecdotal examples.

Adult↗
PubMed1989

A possible harmful late effect of methylprednisolone therapy on a time cluster of optic neuritis.

Clinical records of all patients (n = 26) suffering from optic neuritis during the last 16 years re-evaluated in relation to treatment. The patients were treated in 3 ways: with prednisone; with "pulse" megadoses of methylprednisolone; and untreated. A possibly frightening conversion to multiple sclerosis was seen in the group of patients with methylprednisolone, compared with the other 2 groups.

Adolescent↗
PubMed1989

Suppression of lymphocyte activation by a soluble factor released from the human placental chorionic membrane: chemical analysis and functional characterization.

A heat-resistant factor that markedly and reversibly inhibits human lymphocyte activation was discovered in culture medium of human placental chorion. The chorionic factor inhibits lymphocyte proliferation in response to polyclonal mitogens and in the mixed leukocyte response. The inhibitory action is most effective if the factor is added during the first 24 h of lymphocyte culture and is reversible. The chorionic factor is sensitive to proteinase K, pepsin and bovine pancreatic protease; its activity is completely lost after papain digestion and following treatment with trichloracetic acid (TCA). The factor prevents the expression of IL-2 receptors and class II MHC glycoproteins (HLA-DR) on phytohemagglutinin-stimulated PBMC but does not affect the expression of MHC class I molecules. It inhibits the replication of IL-2-dependent CTLD cells but is without effect on the growth of various human or murine cell lines or acute leukemic cells. Human placental chorion is thus capable of releasing in vitro a nontoxic heat-resistant factor with protein characteristics that reversibly inhibits processes associated with the early stages of lymphoid cell triggering. This factor may play a role in an immunoregulatory mechanism that prevents maternally mediated immune rejection of the conceptus.

Animals↗
PubMed1989

A transfected L-myc gene can substitute for c-myc in blocking murine erythroleukemia differentiation.

We investigated the ability of the proto-oncogene L-myc to substitute for c-myc in blocking murine erythroleukemia differentiation. Murine erythroleukemia cells (line C19) were transfected with recombinant plasmids containing genomic and cDNA fragments of the L-myc gene driven by a Moloney murine leukemia virus long terminal repeat. Clones expressing constitutive high levels of L-myc failed to differentiate in response to the chemical inducer N,N'-hexamethylene bisacetamide (HMBA). The block to differentiation correlated with the level of L-myc expression. Furthermore, transfected clones grown in the presence of inducer for an extended period of time showed an increased level of L-myc expression. These results suggest that functional domains of the c-myc gene involved in differentiation are located in the discrete regions of homology between the c- and L-myc genes.

Acetamides↗
PubMed1989

Major histocompatibility complex class I genes in murine fibrosarcoma IC9 are down regulated at the level of the chromatin structure.

The fibrosarcoma IC9 is deficient in the expression of the major histocompatibility complex class I genes Kb, Kk, and Dk and expresses only the Db molecule. Because class I deficiency may enable tumor cells to escape the immune response by cytotoxic T lymphocytes, we investigated why the class I genes are not expressed. Expression of the silent class I genes could not be induced, but all known DNA-binding factors specific for class I genes could be detected in nuclear extracts of IC9 cells. After cloning of the silent Kb gene from the IC9 cells and subsequent transfection of this cloned Kb gene into LTK- and IC9 cells, normal Kb antigens were expressed on the cell surface of both cell lines. Digestion of the chromatin of IC9 cells with micrococcal nuclease and DNase I showed a decreased nuclease sensitivity of the silent class I genes in comparison with active genes and the absence of DNase I hypersensitive sites in the promoter region of the silent Dk gene. These findings demonstrate that class I expression is turned off by a cis-acting regulatory mechanism at the level of the chromatin structure.

Alleles↗
PubMed1989

Cystine and lysine reabsorption in the isolated perfused rat kidney.

Renal tubular reabsorption of cystine and lysine were studied in the isolated perfused rat kidney to bridge the gap between in vivo clearance studies, and in vitro transport studies of tubule fragments, cells, and brush-border membranes. Lysine was reabsorped by a saturable transport system shared by the dibasics. Cystine was also reabsorbed by a saturable transport system, which was shared in part by the dibasics (maximum inhibition 30%). The lysine threshold (Fmin) was 0.9 mumol.min-1.g-1, with a tubular maximum (TM) of 2.4 mumol.min-1.g-1. The cystine Fmin was 0.06 mumol.min-1.g-1; the TM could not be estimated because it was above the limit of cystine solubility. There was no evidence of cystine "secretion." The gamma-glutamyltransferase inhibitor, AT-125, decreased cystine excretion, but only in the presence of glutathione, glycine, glutamate, and the diabasic amino acids. This suggests that cystine from glutathione degradation at the brush border may contribute to urinary cystine (an explanation of the phenomenon of cystine secretion), but only under certain conditions.

Amino Acids↗
PubMed1989

Effect of uridine on hepatic galactose-1-phosphate uridyltransferase.

Uridine sugar nucleotides are important intermediates in galactose metabolism and may play a role in the long-term galactose toxicity in human galactose-1-phosphate uridyltransferase deficiency galactosemia. Since administration of uridine, a precursor of uridine nucleotides, has been considered as a therapeutic measure, we have investigated the effects of this compound on the activity of rat hepatic transferase. Uridine has been found to be an inhibitor of the enzyme in in vitro studies and to cause an increase in galactose-1-phosphate in liver perfused with galactose which is consistent with physiologic inhibition of the enzyme. Uridine is a partial linear competitive inhibitor of UDPglucose and an uncompetitive inhibitor of galactose-1-phosphate. These findings suggest caution should be applied in giving the compound to subjects with genetically limited transferase activity because of the possibility of inhibiting the small amount of residual enzyme.

Aging↗
PubMed1989

Activity of hepatic galactose-metabolizing enzymes in the pregnant rat and fetus.

The sp act of hepatic galactose-metabolizing enzymes, galactokinase, galactose-1-phosphate uridyltransferase, and uridine diphosphate-4-epimerase were measured in female rats during pregnancy and lactation as well as in fetuses and pups after parturition. Sp act for transferase and epimerase in pregnant rat liver are about 50% higher than that of virgin females, and with the increase in organ size during pregnancy the total hepatic activity is double that of nonpregnant animals. Galactokinase activity decreases somewhat during pregnancy, but total activity is 25% higher than in virgin liver. A Michaelis-Menten kinetic analysis of liver transferase indicates an increase in the maximum velocity of the reaction without a change in Km. Isoelectricfocusing on a high-resolution IEF gel demonstrated similar isozyme patterns. The sp act of the fetal liver enzymes increase to about twice that of the maternal tissue, but total activities are low due to the very small fetal liver size. Sp act of these enzymes in maternal liver fall after delivery, but sp act of galactokinase and transferase are programmed to increase in liver of the growing neonatal animals, reaching levels almost 5-fold higher than found in nonpregnant adult liver. An understanding of factors contributing to the enhanced transferase activity of the liver of pregnant and neonatal rats may contribute to possible ways of augmenting the residual transferase activity of patients with transferase-deficient galactosemia as a therapeutic strategy.

Animals↗
PubMed1989

Effect of anesthesia on the immune system: suppression of the immunogenic capacity of macrophages and of lymphocyte transformation.

Experiments were carried out aimed at investigating the effects of anesthesia without surgery on certain functional components of the immune system. We observed that the immunogenic antigen-presenting capacity of mouse peritoneal macrophages was significantly reduced one week post-anesthesia, with either injected or inhaled anesthetic drugs. On the other hand, an augmentation of the phagocytic activities of these macrophages was manifested. Hence, the impaired immunogenic potency could not be attributed to a reduced antigen uptake. Lymphocyte transformations, i.e., response to PHA and Con A were suppressed, whereas the response to LPS was augmented.

Anesthesia↗
PubMed1989

Evaluation of reduced activity galactose-1-phosphate uridyl transferase by combined radioisotopic assay and high-resolution isoelectric focusing.

Fifty-nine patients referred for testing of galactose-1-phosphate uridyl transferase (GALT) activity were evaluated by a combination of radioisotopic assay and an improved high-resolution isoelectric focusing (IEF) method for determination of individual genotypes. The majority of evaluations (43 of 59) were undertaken because of an abnormal fluorometric GALT screening assay conducted as part of a state newborn galactosemia screening program or as a diagnostic test for an infant with one or more clinical signs of galactosemia. Only 12 of the 43 patients with an abnormal fluorometric screening test were found to have less than 3% GALT activity by quantitative assay, no GALT-staining by IEF, and a clinical history consistent with classical galactosemia. The majority of the remainder (24 of 43) were found to be heterozygotes for galactosemia, the Duarte variant, or both. IEF was found to be a fast and accurate technique for assignment of GALT genotypes in conjunction with quantitative enzymatic assay.

Erythrocytes↗
PubMed1989

[Familial forms of endocrine tumors of the pancreas. Apropos of 4 cases in the same family].

Four cases of endocrine tumors of the pancreas and, more generally, of the diffuse endocrine system, are presented here. Included are all the data relative to the inherited character of the disease covering two generations. Two brothers had Zollinger-Ellison syndrome--one of them probably, the other one proven (first case recorded in France). Both patient's only sons are currently treated for endocrine tumor of the pancreas and Zollinger-Ellison syndrome, respectively.

Adult↗
PubMed1989

Twenty-four-hour structure of sleepiness in morning and evening persons investigated by ultrashort sleep-wake cycle.

"Morning" and "evening" persons, defined according to a modified version of the Horne and Ostberg questionnaire, performed the 7/13 min sleep-waking schedule under attempting sleep condition after sleeping for one night in the laboratory, and under the resisting sleep condition after one night of sleep deprivation. Morning types slept significantly more under the attempting sleep condition and showed an earlier rise in nocturnal sleepiness. After sleep deprivation, morning types had a more distinct sleep propensity pattern with well-defined midafternoon and nocturnal sleep gates. In this condition there was a significant interaction between type and time of day with respect to amount of sleep: morning types slept more during the night, and evening types slept more during the day. Based on their amounts of sleep, subjects were also divided into "sleepy" and "alert" types, which were independent from the chronotypology.

Adult↗