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S Brunner

Publications and source records attributed to S Brunner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cloning and characterization of murine carnitine acetyltransferase: evidence for a requirement during cell cycle progression.

We have employed a newly developed differential screening technique (reverse strand priming) to identify murine carnitine acetyltransferase (CARAT) as a growth- and cell cycle-regulated gene in S3T3 mouse fibroblasts. Sequence analysis of the full-length cDNA clone and homology comparisons have revealed 87% homology to the human CARAT gene. On Northern blots we were able to measure a 2-3-fold induction 18 h after a mitogenic stimulus following serum deprivation as well as after release from a sodium butyrate block. The cell cycle induction pattern of the CARAT gene was analysed in mouse fibroblasts at different stages of the unperturbed cell cycle. Fractions obtained by elutriation of an exponentially growing culture showed a biphasic maximum of transcript abundance in the G1 and G2 phases of the cell cycle. CARAT expression was investigated in several organs of the adult mouse. Among those measured, CARAT expression was highest, relative to liver, in heart muscle (56-fold) and testis (21-fold). Using both conventional antisense oligodeoxynucleotides and novel single-stranded antisense phagemid DNA, we obtained evidence that the CARAT enzyme function is necessary for progression through G1 and into the S-phase of the cell cycle.

Amino Acid Sequence↗
PubMed1997

Humoral mechanisms in T cell vaccination: induction and functional characterization of anti-lymphocytic autoantibodies.

T cell vaccination, the application of syngeneic attenuated T cells, has been shown to prevent effectively and treat experimental autoimmune diseases, but its mechanisms of action are poorly understood. Here we present data on the induction of a humoral anti-T cell response by T cell vaccination, capable of strongly inhibiting T cell proliferation and of ameliorating experimental autoimmune disease. T cell vaccination in the Lewis rat induced autoantibodies reactive with several syngeneic T cell proteins. These autoantibodies were not detectable in normal Lewis sera as assessed by immunoblotting and flow cytometry with intact syngeneic T cells. The autoantibody reactivity was not restricted to one idiotype, was detected as early as 1 week after vaccination and was dominated by IgG, suggesting the boosting of a naturally preformed humoral network by T cell vaccination. Recovery from passively or actively induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat, too, could be shown to be associated with the development of anti-T cell autoantibodies. In vitro, both the post-EAE and the post-vaccination sera had a strong suppressive effect on the proliferation of syngeneic T cell clones. This inhibition was shown to be mediated by antibodies and to be partly complement-dependent. In vivo, both kinds of sera were able to ameliorate EAE. This protective effect of the post-vaccination sera was not idiotype-specific, since sera obtained after T cell vaccination with an unrelated T cell clone were similarly effective in suppressing EAE. These results suggest that anti-lymphocytic antibodies might play an immunoregulatory role that can be positively manipulated by T cell vaccination.

Animals↗
PubMed1996

Effects of in utero substance exposure on infant neurobehavior.

OBJECTIVE: This study had two objectives: (1) to assess infant behavior by using the NICU Network Neurobehavioral Scale (NNNS), an assessment designed specifically for prenatally drug-exposed infants; and (2) to control for the effects of polydrug use involving alcohol, marijuana, and cigarettes on the neurobehavioral status of the newborn infant. METHODS: The subjects and controls in this study were full-term infants of appropriate gestational age with no medical problems. At 1 to 2 days of age, 20 infants exposed to cocaine, alcohol, marijuana, and cigarettes; 17 infants exposed to alcohol and/or marijuana and cigarettes; and 20 drug-free infants were evaluated by using the Neonatal Intensive Care Unit Network Neurobehavioral Scale. The data were reduced to reflect clinically defined categories of neurobehavioral function and were analyzed by using analysis of variance and chi 2 statistics. RESULTS: Cocaine-exposed infants showed increased tone and motor activity, more jerky movements, startles, tremors, back arching, and signs of central nervous system and visual stress than unexposed infants. They also showed poorer visual and auditory following. There were no differences in how the examination was administered to cocaine-exposed and nonexposed infants. Reduced birth weight and length were also observed in cocaine-exposed infants. CONCLUSION: Differences attributable to cocaine-exposed infants were related to muscle tone and motor performance, following during orientation, and signs of stress. However, cocaine-exposed infants were not more difficult to test, nor did they require an alteration in the examination. Both neurobehavioral patterns of excitability and lethargy were observed. Findings may have been due to the synergistic effects of cocaine with alcohol and marijuana.

Cannabis↗
PubMed1993

Neuromodulation mediated by neurokinin-1 subtype receptors in adult rabbit airways.

The neuromodulatory actions of Septide, a selective neurokinin-1 (NK-1) agonist, and substance P (SP) were investigated in isolated rabbit tracheal smooth muscle (TSM) segments. The tissues were placed in organ baths containing modified Krebs-Ringer solution and contracted with either the agonists or electrical field stimulation (ES) with frequencies ranging from 1 to 50 Hz. The neutral endopeptidase (NEP) inhibitor, phosphoramidon (10(-6) M), had no significant effect on Septide-mediated contractions. Septide-mediated contractions were augmented in the presence of neostigmine, eliminated in the presence of atropine, and diminished in the presence of tetrodotoxin. Both SP and Septide increased ES-induced contractions in a dose-dependent manner. On the other hand, the presence of both Septide and SP did not further augment this neuromodulatory action. After NK-1 desensitization, Septide-mediated contractions were also virtually eliminated; however, the peptide's neuromodulatory action was unaffected. In contrast, the presence of GR-82334, a selective NK-1 antagonist, eliminated Septide's neuromodulatory activity. These findings provide evidence that 1) NK-1 receptors facilitate both the direct release of ACh as well as augment the release of ACh by ES and 2) the cholinergic pathways involved with these two processes may represent different mechanisms.

Acetylcholine↗
PubMed1992

Autoantibodies in experimental autoimmune hepatitis.

Experimental autoimmune hepatitis (EAH) can be induced in mice by immunization with syngeneic soluble liver antigens in complete Freund's adjuvant. It has previously been shown that autoreactive T cells play an important role in this animal model of autoimmune hepatitis. We have studied the occurrence of liver autoantibodies in EAH. Characteristic autoantibodies appeared several weeks after disease induction and antibody titres continued to rise when histological and biochemical signs of disease activity had already regressed. Autoantibodies in EAH seemed to recognize autoantigens other than those present in autoimmune chronic active hepatitis patients. We conclude that autoantibodies arise in experimental autoimmune hepatitis but that these autoantibodies do not play a critical role in the pathogenesis of the disease.

Animals↗
PubMed1990

[Segev health promotion project in Jerusalem elementary schools].

The health-promotion and education project, Segev, is an Israeli version of the American Health Foundation's Know Your Body project. The aim of this cohort study was to change knowledge, attitudes, health behavior and risk factors for cardiovascular disease in elementary school children. We present the results of questionnaires about knowledge of, and attitudes to health in 656 Jewish children who started first grade in 1983-4 and completed 4 questionnaires in the first and third grades. The results indicate a statistically significant increase in knowledge and attitude scores in the experimental group after 1 and 3 years of intervention. They indicate that changes in knowledge of, and attitudes to health are possible after even a relatively short school health education program.

Attitude to Health↗
PubMed1990

Corynebacterium parvum (Propionibacterium acnes): an inducer of tumor necrosis factor-alpha in human peripheral blood mononuclear cells and monocytes in vitro.

The present study investigates the potential capacity of the immunostimulant Corynebacterium parvum (C.p.) to induce tumor necrosis factor-alpha (TNF-alpha) in human peripheral blood mononuclear cells (PBMC) and blood monocytes (BMo) in vitro. Both at the mRNA and protein level, stimulation of PBMC and BMo upon C.p. induces TNF-alpha. Compared to the hitherto used TNF-alpha inducers in vitro such as Sendai virus, phytohemagglutinin or lipopolysaccharide the C.p. stimulus displayed a threefold stronger induction of TNF-alpha production (p less than 0.001). Using C.p. as an inducer it was possible to demonstrate that TNF-alpha production is regulated by prostaglandin E2; preincubation of the cells with prostaglandin E2 resulted in a reduced C.p.-mediated TNF-alpha production (p less than 0.001). Coincubation of interferon-gamma (IFN-gamma) together with C.p. led to an enhanced release of TNF-alpha, supporting the assumption that C.p. is a potent TNF-alpha inducer. The additive effect of IFN-gamma and TNF-alpha on the receptor level was demonstrated by addition of IFN-gamma antibodies to the PBMC cultures. Under these conditions TNF-alpha production, stimulated by C.p. and IFN-gamma, was decreased by 30%, compared to the production in assays supplemented with C.p. alone. From these data we conclude that C.p. is a new inducer of TNF-alpha in vitro and a useful tool to study TNF-alpha production of PBMC and BMo from either healthy donors or from patients.

Blotting, Northern↗
PubMed1990

Primary prevention of cardiovascular diseases in childhood: changes in serum total cholesterol, high density lipoprotein, and body mass index after 2 years of intervention in Jerusalem schoolchildren age 7-9 years.

A school health education and promotion program, the Israeli version of the American Health Foundation's "Know Your Body" program, was developed by the Department of Public Health of the Municipality of Jerusalem in 1983. Eight experimental and eight control schools participated in this cohort study of Arab and Jewish first-grade children. After the first 2 years of intervention, comparison of experimental and control groups showed a significant increase in serum high density lipoproteins among Jewish children and a decrease in serum total cholesterol and body mass index among both Jewish and Arab children. These results indicate that changes in cardiovascular disease risk factors such as blood total cholesterol, high density lipoproteins, and body mass index are possible after a health education program is introduced to first-grade students for a relatively short period of time.

Body Mass Index↗
PubMed1981

Protein degradation during preimplantation development of the mouse.

The half-lives of labelled proteins were determined for mouse preimplantation embryo stages from the germinal vesicle oocyte to the early blastocyst. While no significant differences were found among half-lives for 1-cell stages, or among half-lives for cleavage stages, a significant (P less than 0.05) 28% decrease in half-life was observed between the 1-cell and the cleavage stages. Labelled protein half-lives were 18.2 and 13.1 h for the 1-cell and cleavage stages respectively. Fertilization probably initiates this increase in protein degradation rate although no significant decrease was detected until after the first cleavage.

Animals↗
PubMed1980

[Serodiagnosis of human Yersinia infections. Preliminary results].

Preliminary data are reported on experience with newly developed complement-fixing (CF) antigens prepared from cultures of type 3 and type 9 Yersinia enterocolitica and from Yersinia pseudotuberculosis. Antigens were immunologically potent and not anti-complementary, thus making it possible to obtain satisfactory serologic tests. The results may be summarized as follows: 1. Yersinia CF antigens do not react with sera from healthy blood donors. There was only one low titer reaction with type 9 antigen among more than 300 serum samples tested. 2. There was a high degree of correlation between results of the agglutination tests and those obtained by CF. 3. There is no cross-reactivity by CF among the three Yersinia antigens if human sera are tested. A complete crossing was, however, obtained between type 9 Yersinia and Brucella abortus. 4. Hyperimmune sera frequently showed marked cross-reactivities in both CF and agglutination tests. 5. Human sera positive for various Salmonellae do not react in the CF tests with Yersinia antigens. It is felt that the new CF antigens may become an important tool for the detection of antibodies against Yersinia enterocolitica in the diagnosis of infectious diseases.

Antibodies, Bacterial↗
PubMed1979

Protein degradation in the mouse blastocyst.

The degradation characteristics of 56 individual newly synthesized proteins of the Day 4 mouse blastocyst have been examined employing double isotope labeling of proteins for half-life measurement and two-dimensional electrophoresis for separation of proteins. The half-lives ranged from 1 to approximately 30 h with a mean of 12.4 h. Several proteins appeared to have half-lives greater than 30 h but decay times were insufficient to provide precise information for these proteins. The results suggest there is a tendency for proteins with acidic isoelectric points to be degraded more rapidly than basic proteins, and for high molecular weight proteins to be degraded more rapidly than low molecular weight proteins. Although the regressions of these two parameters on half-life were not significant, the direction and magnitude of the trends were similar to those previously described for liver proteins. Two specific proteins, tubulin and actin, were tentatively identified, and their half-lives determined. Tubulin had a half-life of 9.0 h. The half-lives of the provisionally identified gamma, beta, and alpha forms of actin were 2.2, 8.7, and 5.4 h respectively.

Actins↗
PubMedDate not supplied

Polycation-based DNA complexes for tumor-targeted gene delivery in vivo.

BACKGROUND: Efficient and target-specific in vivo gene delivery is a major challenge in gene therapy. Compared to cell culture application, in vivo gene delivery faces a variety of additional obstacles such as anatomical size constraints, interactions with biological fluids and extracellular matrix, and binding to a broad variety of non-target cell types. METHODS: Polycation-based vectors, including adenovirus-enhanced transferrinfection (AVET) and transferrin-polyethylenimine (Tf-PEI), were tested for gene delivery into subcutaneously growing tumors after local and systemic application. DNA biodistribution and reporter gene expression was measured in the major organs and in the tumor. RESULTS: Gene transfer after intratumoral application was 10-100 fold more efficient with Tf-PEI/DNA or AVET complexes in comparison to naked DNA. Targeted gene delivery into subcutaneously growing tumors after systemic application was achieved using electroneutral AVET complexes and sterically stabilized PEGylated Tf-PEI/DNA complexes, whereas application of positively charged polycation/DNA complexes resulted in predominant gene expression in the lungs and was associated by considerable toxicity. CONCLUSION: For systemic application, the physical and colloidal parameters of the transfection complexes, such as particle size, stability, and surface charge, determine DNA biodistribution, toxicity, and transfection efficacy. By controlling these parameters, DNA biodistribution and gene expression can be targeted to different organs.

Adenoviridae↗
PubMedDate not supplied

Transfection of epithelial cells is enhanced by combined treatment with mannitol and polyethyleneglycol.

BACKGROUND: Gene transfer efficiency drops significantly when polarized mammary epithelial cells are transfected instead of actively growing cells. However, fully differentiated cells are the targets for gene transfer in many in vivo applications. Therefore, a simple and effective method for the transfection of polarized mammary epithelial cells in confluent monolayers was developed. METHODS: Reporter gene plasmids were complexed with polyethylenimine with an average molecular weight of 25 kDa (PEI 25), or other agents, to transfect confluent monolayers of ovine mammary epithelial cells (OMEC II) or human carcinoma cells (CaCo-2) in vitro. The improved technique included pretreatment of the cells with a hyperosmotic mannitol solution (7%) which caused a loosening of the tight contacts between the cells. Alternatively, the mannitol shock could be replaced by a short treatment with trypsin or EDTA. In addition to the pretreatment, 12.5% polyethyleneglycol with an average molecular weight of 8000 kDa (PEG 8000) was included in the transfection mixture containing the DNA complexes. RESULTS: The combined application of mannitol and PEG resulted in a very reliable 5- to 30-fold increase in reporter gene expression in OMEC II and CaCo-2 cells, but not K562 cells (an example of another cell type). The improved technique can also be combined with other polymer-based transfection agents. The transfection rate was enhanced for confluent monolayer cells with fully developed epithelial polarity but also for subconfluent, growing epithelial cell cultures. CONCLUSIONS: A novel transfection protocol for epithelial cells is presented. The combined treatment of cells with mannitol and polyethyleneglycol results in substantial enhancement of in vitro transfection of epithelial cell lines.

Animals↗