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Biomedical subjects

E Kaminsky

Publications and source records attributed to E Kaminsky.

17 recordsLinked to original sources
PubMed2000

Induction of mRNA for tumor necrosis factor-alpha and interleukin-1 beta in mice brain, spleen and liver in an animal model of Shigella-related seizures.

BACKGROUND: The pathogenesis of neurological symptoms, the most common extraintestinal complication of childhood shigellosis, is unclear. To elucidate the mechanisms involved, we developed an animal model and demonstrated that TNF alpha and IL-1 beta play a role. OBJECTIVES: To determine whether TNF alpha and IL-1 beta genes are expressed in the brain following peripheral administration of Shigella dysenteriae 60R. METHODS: Expression of mRNA for TNF alpha and IL-1 beta was examined in the brain structures (hypothalamus and hippocampus) and peripheral organs by reverse transcriptase polymerase chain reaction, at different time points after intraperitoneal injection of S. dysenteriae sonicate. RESULTS: In our animal model of Shigella-related seizures, TNF alpha and IL-1 beta mRNA were induced in the brain, spleen and liver already 1 hour after injection of S. dysenteriae sonicate. The expression of TNF alpha and IL-1 beta mRNA in spleen, hippocampus and hypothalamus decreased after 6 h and increased again at 18 h post-injection. CONCLUSIONS: Local production of TNF alpha and IL-1 beta in the brain may be involved in the enhanced seizure response of mice after administration of S. dysenteriae. It is possible that intracerebral production of TNF alpha and IL-1 beta plays a role in neurological disturbances of human shigellosis.

Animals↗
PubMed1999

Role of nitric oxide in the enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae.

Convulsions and encephalopathy are frequent complications of childhood shigellosis. We studied the role of nitric oxide (NO) in Shigella-related seizures in an animal model. Pretreatment of mice with Shigella dysenteriae 60R sonicate elevated serum NO levels and enhanced the convulsive response to pentylenetetrazole (PTZ), as indicated by a higher mean convulsion score and a higher number of mice responding with seizures. Treatment of the mice with S-methylisothiourea sulfate (SMT), a potent inhibitor of inducible NO synthase (NOS), prevented the elevation of serum NO levels and concomitantly reduced the enhanced response to PTZ. The mean convulsion scores were 0.7, 0.7, 1.3, and 0.8 for mice treated with saline, saline and SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.001 for 60R sonicate versus saline and P = 0.013 for 60R sonicate versus 60R sonicate with SMT). The corresponding seizure rates were 40, 44, 75, and 47% for saline, saline with SMT, S. dysenteriae 60R sonicate, and S. dysenteriae 60R sonicate with SMT, respectively (P = 0.0004 for 60R sonicate versus saline and P = 0.005 for 60R sonicate versus 60R sonicate with SMT). In contrast, injection of N-nitro-L-arginine, a selective inhibitor of constitutive NOS, neither abolished the elevation of serum NO nor attenuated the enhancement of seizures. These findings indicate that NO, induced by S. dysenteriae 60R sonicate, is involved in enhancing the susceptibility to seizures caused by S. dysenteriae.

Animals↗
PubMed1999

Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae.

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h. This was indicated by a significantly higher mean convulsion score and an increased number of mice responding with clonic-tonic seizures in the Shigella-pretreated group. Preinjection of mice with anti-murine TNF-alpha (anti-mTNF-alpha) or anti-murine IL-1beta (anti-mIL-1beta) 30 min prior to administration of Shigella sonicate abolished their enhanced response to PTZ at 7 h. Mean convulsion scores were reduced by anti-mTNF-alpha from 1.2 to 0.8 (P = 0.017) and by anti-mIL-1beta from 1.3 to 0.7 (P = 0.008). Preinjection of anti-mTNF-alpha also reduced the percentage of mice responding with clonic-tonic seizures, from 48 to 29% (P = 0.002), and preinjection of anti-mIL-1beta reduced it from 53 to 21% (P = 0. 012). Neutralization of TNF-alpha or IL-1beta did not protect the mice from death due to S. dysenteriae 60R. These findings indicate that TNF-alpha and IL-1beta play a role in the very early sensitization of the central nervous system to convulsive activity after S. dysenteriae administration. Similar mechanisms may trigger neurologic disturbances in other infectious diseases.

Animals↗
PubMed1996

Induction of nitric oxide production in mouse macrophages by Shiga toxin.

Host mediators play an important role in the pathogenesis of shigellosis and Shiga toxin toxicity. Nitric oxide (NO) production in mouse peritoneal macrophages and in the macrophage J744 cell line in response to purified Shiga toxin and lipopolysaccharide (LPS) from Shigella flexneri were studied. Shiga toxin induced NO production in a dose-dependent manner up to 800 ng/ml. Detectable levels of NO were present as early as 4 h after induction and continued to increase during 72 h; Shiga toxin induced greater NO production with time than did LPS. Pre-treatment of Shiga toxin (400 ng/ml) or LPS (10 ng/ml) with polymyxin B, which inactivates LPS, reduced their ability to induce NO by 28% and 96%, respectively. Induction in the presence of anti-TNF alpha antibodies did not reduce the amount of NO in the supernate. These studies showed that Shiga toxin induces NO production in murine macrophages.

Animals↗
PubMed1996

Induction of tumor necrosis factor and nitric oxide by Shigella strains isolated from patients with or without neurologic manifestations.

The pathogenesis of the Shigella-associated neurological symptoms is unclear. We examined the potential role of host factors. Sonicates of Shigella strains isolated from children with and without neurologic disturbances were compared regarding their ability to induce tumor necrosis factor (TNF) and nitric oxide (NO) in vitro, in mouse macrophage J744 cell line. The mean concentrations of TNF (14.6 vs. 4.4 ng/ml) and NO (7.4 vs. 3.7 microM) induced were higher in response to strains isolated from children with neurologic complications; the differences were not statistically significant. TNF was also measured in plasma of children with shigellosis, and was found to be elevated in all patients. The mean concentration of TNF in plasma of children with neurologic manifestations was higher than that of children with no neurologic symptoms (450 vs. 138 pg/ml, P <0.05). It is concluded that TNF and NO may play a role in the development of neurologic manifestations of shigellosis.

Animals↗
PubMed1995

The immunosuppressive human placental ferritin subunit p43 is produced by activated CD4+ lymphocytes.

Human placental ferritin is an immunosuppressive protein composed of a 43-kDa subunit (p43) and ferritin light chains. Its physiological action seems to be downregulation of the immune response of the mother against her embryo. Elevated levels of p43 in serum are associated with pregnancy, lymphomas, breast cancer, and AIDS. Although it is known that p43 is produced by activated T lymphocytes, the specific T-lymphocyte subset involved is unknown. p43 is measured by enzyme-linked immunosorbent assays with CM-H-9 monoclonal antibody specific for p43. We studied the de novo biosynthesis of p43 by isolated activated CD4+ and CD8+ T lymphocytes in a normal donor and in a patient with elevated levels of p43 in serum. The results indicated that p43 was synthesized by activated CD4+ lymphocytes from the normal donor (0.45% of the total de novo proteins) but that its biosynthesis by CD8+ lymphocytes was below the level of detection. The activated CD4+ lymphocytes from the patient with elevated levels of p43 in serum overproduced p43 (3.8% of the nascent proteins). Since it was shown that a subset of CD8+ lymphocytes has receptors for p43, the latter may be considered an immunoregulatory cytokine produced mainly by activated CD4+ lymphocytes.

Adolescent↗
PubMed1994

The effect of shiga toxin and sonicates of Shigella isolates from children with neurologic manifestation on neuroblastoma cell lines.

Although neurologic manifestations are frequent during childhood shigellosis, their pathogenesis is unclear and controversial. Shiga toxin and other cytotoxins are often implicated, but their effect on neuronal cells has not been determined. We examined the effect of purified Shiga toxin and sonicates of Shigella isolates from children with neurologic symptoms on well-characterized human neuroblastoma cells in vitro. Quantitative determinations showed high cytotoxicity of Shiga toxin on HeLa cells (1.2 x 10(6) CD50/mg purified toxin), but no effect on LA-N-1, LA-N-5 and IMR neuroblastoma cell lines. Pretreatment with tumor necrosis factor, which increases expression of the Shiga toxin receptor, globotriosyl ceramide, in endothelial cells and enhanced Shiga toxin cytotoxicity, did not affect the susceptibility of neuroblastoma cells to the toxin. Low dilutions (up to 1:16-1:64) of sonicates of Shigella isolates from children with neurologic symptoms caused agglutination of neuroblastoma cells, but no cell killing was observed morphologically. This study shows that Shiga toxin does not exhibit cytotoxic activity on the human neuroblastoma cell lines examined, neither do sonicates of relevant Shigella strains. The mechanism and significance of the agglutination activity on neuroblastoma cells should be further studied.

Bacterial Toxins↗
PubMed1992

Mosaicism in 45,X Turner syndrome: does survival in early pregnancy depend on the presence of two sex chromosomes?

Cytogenetic and molecular genetic findings in 91 patients with Turner syndrome are reported. In 87 patients, chromosome studies were carried out both in lymphocyte and fibroblast cultures. Mosaicism was demonstrated in 58 of these patients (66.7%), whereas only 18 (20.7%) were apparent non-mosaic 45,X, and 11 patients (12.6%) showed non-mosaic structural aberrations of the X chromosome. Among the mosaic cases 16 (18.4% of all patients) displayed a second cell line containing small marker chromosomes. The association of Y-specific chromosomal material with the presence of marker chromosomes was demonstrated in 6 out of 7 mixoploid fibroblast cell lines by polymerase chain reaction amplification and by Southern-blot analysis. The observation of ring formation and morphological variability in vivo and in vitro, and the continuous reduction in the percentage of cells containing marker chromosomes in longterm cultivation experiments indicated an increased instability of marker chromosomes. The findings suggest that in vivo selection of structurally altered sex chromosomes exists. Thus, the observation of apparent non-mosaic 45,X chromosomal complements in liveborn individuals with Turner syndrome does not contradict the hypothesis that some degree of mosaicism is necessary for survival in early pregnancy.

Blotting, Southern↗
PubMed1985

Dimethyl sulfoxide-induced differentiation does not alter tumorigenicity of neuroblastoma cells.

It has been shown that agents that are known to be scavengers of hydroxyl radicals may induce differentiation and inhibit growth of murine neuroblastoma cells in tissue culture. The present study tests dimethyl sulfoxide as a differentiation agent of the human neuroblastoma cell lines LA-N-1 and murine neuroblastoma NIE-115. Results indicate that DMSO induces morphologic and biochemical differentiation of neuroblastoma cells coupled to growth inhibition and inhibition of colony formation in semi liquid tissue culture systems. DMSO treatment in vitro had no effect on tumorigenicity of NIE-115 cells. In vivo DMSO treatment of athymic nude mice with transplanted LA-N-1 human neuroblastoma tumors has not affected tumor size or animal survival. No diminishing effect of natural killer cell activity could be attributed to DMSO treatment.

Animals↗
PubMed1979

Rabbit skeletal muscle F-actin can be stable at low ionic strength, provided trace amounts of Ca2+ are absent.

Addition of low concentrations (0.2--2.0 mM) of EGTA to rabbit skeletal muscle G-actin in the presence of ATP caused increase in viscosity. The effect is probably due to chelation of Ca2+. EGTA-polymerized actin was sedimented in the ultracentrifuge as a pellet which could be depolymerized in the presence of Ca2+ and then repolymerized. Electron microscopy indicated that formation of filamentous actin which appears to be somewhat more flexible than F-actin obtained by polymerization with KCl. The EGTA-polymerized actin was dissociated by DNAase I faster than KCl-polymerized actin. F-Actin can thus be stable also in very low ionic strength media if Ca2+ is removed whereas for G-actin to be the only form of the protein in such media, micromolar concentrations of Ca2+ must be present.

Actins↗