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G Messer

Publications and source records attributed to G Messer.

At least 55 records · Page 3Linked to original sources
PubMed1992

Polymorphism of the tumor necrosis factor region in relation to disease: an overview.

HLA antigens have been shown to be associated with several immunoinflammatory diseases. The mechanisms by which these antigens confer susceptibility to disease continue to be of major interest. Rapid progress has been made in the elucidation of the structure and function of class I and II MHC molecules, and several genes located within the HLA complex have been identified which are potentially involved in immunologic processes. Because of the HLA localization of the TNF-alpha and -beta genes and the biologic activities of the gene products, recent investigation has focused on a possible role of polymorphic TNF genes in the pathogenesis of HLA-associated diseases. Allelic variations have only been detected in the TNF-beta gene. No evidence has been found so far that a particular TNF-beta allele contributes significantly in the susceptibility to the diseases studied. Although it has been postulated that the TNF beta*2 allele contributes to susceptibility to IDDM in HLA-DR3, 4 heterozygous individuals, a larger group of HLA-typed patients and controls is needed to provide more conclusive evidence for this hypothesis. The increasing number of genes of unknown function encoded by the class III region leaves the possibility that the observed HLA associations in some diseases may be related to the presence of these genes. In AS, the lack of association with the TNF-beta alleles furthermore supports the function of the HLA-B27 molecule in the disease and underlines the improbability that HLA-B27 is merely a marker for a closely linked susceptibility gene.

Cytokines↗
PubMed1991

Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production.

Since a dysregulated synthesis of tumor necrosis factor alpha (TNF-alpha) may be involved in the pathogenesis of autoimmune diseases, it was of interest to precisely locate the recently reported NcoI restriction fragment length polymorphism (RFLP) of the TNF-alpha region. However, by mapping of 56.8 kb of overlapping cosmid clones and direct sequencing, we could localize the polymorphic NcoI restriction site within the first intron of the TNF-beta gene and not in the TNF-alpha gene. To study whether regulatory mechanisms are affected by this polymorphism, we analyzed the TNF-alpha/TNF-beta production of phytohemagglutinin-stimulated peripheral blood mononuclear cells of individuals homozygous for the TNF-beta NcoI RFLP by ELISA and concomitant Northern blot analysis. On days 2-4 after stimulation with mitogen, the TNFB*1 allele corresponding to a 5.3-kb NcoI fragment presented with a significantly higher TNF-beta response. A mRNA analysis demonstrated that higher protein levels of TNF-beta correlate also with increased amounts of TNF-beta transcripts. No allelic association was found in respect to TNF-alpha production. To further investigate a possible allelic influence on transcription, we determined the DNA sequence of 2 kb of the 5' portion of our cloned TNFB*2 allele and compared it with the available TNF-beta sequences. By computer-aided recognition motif search of DNA binding factors, we report putative binding sites conserved between mouse and man in the 5' flanking region as well as in intron 1 of the TNF-beta gene, found also in other cytokine promoter sequences. In addition, by polymerase chain reaction amplification and sequencing of 740 bp of the 5' part of TNF-beta of individuals typed homozygously for the NcoI RFLP, we could show that amino acid position 26 is conserved as asparagine in the TNFB*1 and as threonine in the TNFB*2 sequence. A previously reported, EcoRI RFLP in the 3' untranslated region of TNF-beta does not segregate with either of the two alleles. Thus, four TNFB alleles can be defined at the DNA level.

Alleles↗
PubMed1991

Cell-free supernatants of sarcoid alveolar macrophages suppress proliferation of sarcoid alveolar fibroblasts.

We have reported that alveolar macrophages (AM) isolated from sarcoidosis (SA) patients, as well as cell-free supernatants of these macrophages, markedly suppressed mitogenic stimulation of peripheral blood lymphocyte (PBL). We now show that cell-free supernatants of AM originating from sarcoidosis patients also suppress [3H]thymidine incorporation by fibroblast (Fb) cultures resulting from bronchoalveolar lavages (BAL) of SA: 40.6% inhibition compared with only 8.2% by supernatants of AM obtained from nonsarcoid controls. The clones of proliferating Fb appeared in cultures of BAL cells after most of the macrophages were detached from the tissue culture surface and actively synthesized collagen, as demonstrated by ultrastructural studies. In confirmation with previously reported results, the same supernatants from AM of SA patients also suppressed mitogenic stimulation of PBL (35.7% inhibition of [3H]thymidine incorporation compared with only 16.3% inhibition by control supernatants). They also contained high amounts of IL-1 (178 compared to 9.2 U/ml of control supernatants), whereas the PGE2 content was within normal levels (0.28 compared to 0.19 ng/ml/10(5) cells in control supernatants). It is concluded that AM from SA patients release a factor(s) which suppresses the proliferation of alveolar fibroblasts.

Adult↗
PubMed1991

Allelic variation in the TNF-beta gene does not explain the low TNF-beta response in patients with primary biliary cirrhosis.

Autoimmune disorders in humans are often associated with particular alleles of major histocompatibility genes. However, the chronic inflammatory liver disease primary biliary cirrhosis (PBC) has not been found to be correlated with certain haplotypes so far. Interestingly, an impaired production of tumour necrosis factor beta (TNF-beta) upon mitogen stimulation was observed for PBC patients, especially in the immunologically active stages of the disease. Furthermore, the identification of alleles of the TNF-beta gene which differ in one unique amino acid, and in the production of TNF-beta after phytohaemagglutinin stimulation, has prompted the idea of a possible linkage between the impaired TNF-beta response in PBC and the genetic prevalence of a certain TNF haplotype. We report here a rapid method for typing the TNFB*1 and TNFB*2 genes by a standard polymerase chain reaction. PBC patients (n = 60) as well as randomized healthy controls (n = 179) of the Munich area were studied for the occurrence of the TNF alleles. No deviation was found in the PBC collective (0.7) for the TNFB*2 distribution when compared with the control (0.67).

Alleles↗
PubMed1991

Intact cells on the laser handpiece--a non-contact contamination.

Material adhering to the handpiece of the laser instrument was collected and analysed. Examination of semithin sections of the material by light microscopy revealed small clusters of clearly defined whole cells among the abundant debris. Electron microscopy of the cells revealed the presence of cell membranes, cytoplasm and organelles such as mitochondria. This could mean that infected cells or virus particles could adhere to the laser instrument or the hands of the operator as well. The medical implication of this finding requires serious consideration in regard to risks of infection from this procedure, to both patient and clinical personnel.

Cells↗
PubMed1991

[Middle cerebral artery fetal velocimetry: criteria for extraction in severe growth retardation].

Traditional fetal extraction criteria based on the cardiotocogram (group 1) probably occur too late to serve as extraction criteria in cases of severe growth retardation. We suggest that Doppler ultrasound of the middle cerebral artery (M.C.A.) (group 2) would be used to assess the optimal moment for fetal extraction. This method has enabled us to modify perinatal mortality from 37% to 0% (p less than 0.01). The percentage rate of cerebral hemorrhage and/or neurological sequelae was 41% (9/22) in the first group whereas no infant in group 2 or 3 (control group) had these complications. The percentage rate of neonatal complication was 67% in group 1 versus 28% in group 2 (p less than 0.01). Group 1 spent 53 days (+/- 35) in intensive neonatal care unit versus 43 days (+/- 22) for group 2. Neonatal outcome was quite similar between group 2 and the control group. Cerebral Doppler could allowed us to extract severe IUGR fetuses just before cerebral ischemia and irreversible tissue damage.

Cardiotocography↗
PubMed1990

Tumor necrosis factor beta (TNF-beta) induces binding of the NF-kappa B transcription factor to a high-affinity kappa B element in the TNF-beta promoter.

The expression of the gene encoding tumor necrosis factor beta (TNF-beta) (lymphotoxin) is induced in T cells by various extracellular stimuli. We noticed that most such stimuli also activate the NF-kappa B transcription factor. Here we demonstrate binding of purified human NF-kappa B to a sequence within positions -98 to -88 (5'-GGGGCTTCCCC-3') of the TNF-beta promoter, which is conserved between the human and mouse genes. Also the NF-kappa B from the human T-cell line Jurkat, activated upon phytohemagglutinin (PHA)/phorbol 12-myristate 13-acetate (PMA/TPA) treatment in vivo or upon deoxycholate treatment in vitro, binds with high affinity to the sequence in the TNF-beta promoter. Apart from a single mismatch, the site is identical to a cis-activating element that is involved in the inducible expression of the MHC class I gene H-2Kb and which interacts with both the inducible NF-kappa B transcription factor and the constitutive factor KBF1/H2TF1, as we demonstrate here for the site in the TNF-beta promoter. The high homology of the well characterized H-2Kb enhancer sequence with the TNF-beta site with regard to sequence and factor binding strongly supports a physiological role for NF-kappa B in the inducible expression of the TNF-beta gene. Our observation that the TNF-beta protein can rapidly induce the DNA-binding activity of NF-kappa B in Jurkat T cells and transiently increase TNF-beta mRNA levels suggests that NF-kappa B can mediate a positive autoregulation of TNF-beta synthesis.

Base Sequence↗
PubMed1990

Structural characteristics of the 5' region of the human ICAM-1 gene.

The ICAM-1 glycoprotein, one of the major cellular adhesion molecules, exhibits a diverse and highly regulated tissue distribution. To better understand the regulatory mechanisms underlying its particular expression pattern, we have cloned the ICAM-1 gene from human leukocyte libraries. By hybridization with various DNA probes derived from different regions of the ICAM-1 cDNA, several clones were identified and isolated. Clone HWB 3R1, containing a 15kb DNA insert, was selected for further characterization. The HWB 3R1 clone hybridized with probes corresponding to the 3' as well as the 5' region of the ICAM-1 cDNA and gave rise to ICAM-1 expression after transfection into the ICAM-1 deficient MJP17 melanoma cell line. The identity of the expressed ICAM-1 was verified by reaction with five different monoclonal antibodies specific for ICAM-1. Sequence analysis of about 1.2kb of DNA around the ATG start codon revealed putative binding sites for various transcription factors situated in the 5' untranslated region as well as within the first intron. These include SP-1, AP-1 and NF-kB binding sites as well as interferon and retinoic acid responsive elements.

Amino Acid Sequence↗
PubMed1989

A physical map including a new class I gene (cda12) of the human major histocompatibility complex (A2/B13 haplotype) derived from a monosomy 6 mutant cell line.

To avoid interpretative problems due to restriction fragment length polymorphisms, the monosomy 6 mutant cell line BM19.7 was employed to establish a molecular map of the human major histocompatibility (HLA) complex in the A2,B13,Bw4,DRw6,DRw52,DQw1,DPw2 haplotype. Results were obtained mainly by field-inversion gel electrophoresis and Southern blotting techniques. The map extends to 4800 kb and includes the HLA complex with a length of 4200 kb. Five HTF islands could be positioned on the map. The class I region has a size of about 2000 kb and includes nonclassical HLA class I genes, some of which must be localized within 200 kb telomeric of HLA-A. A new class I gene, cda12, distinct from HLA-A, HLA-B, or HLA-C, has been localized within 50 kb from HLA-A. The class I region contains a gap of about 500 kb, just telomeric of HLA-C, in which further class I genes could not be detected. The class II region has a size of 1000 kb, which is separated from the class I region by about 1200 kb. The 5' end of the HLA-B gene is situated centromeric, giving an orientation opposite to that of the TNFA and TNFB loci. The estimated length of the HLA complex correlates well with its size determined cytogenetically using mutant cell lines with interstitial deletions.

Cell Line↗
PubMed1988

Malignant fibrous histiocytoma arising in a scar.

We describe a case of a malignant fibrous histiocytoma (MFH) arising in a scar. Previous reports have described this tumor associated with radiation, bone infarcts, foreign body reaction and in previous surgery sites. The present case emphasizes the correlation between chronic reparative reactions with external irritation and the appearance of this tumor.

Aged↗
PubMed1987

Cytostatic effect of DL-alpha-difluoromethylornithine against Plasmodium falciparum and its reversal by diamines and spermidine.

DL-alpha-difluoromethylornithine (DFMO) inhibited ornithine decarboxylase (ODC) activity and arrested the growth of Plasmodium falciparum at the early trophozoite stage. The inhibition of ODC activity did not result in the formation of an alternative diamine such as cadaverine. When putrescine or spermidine were added to the parasites grown in culture, the arrest was reversed, and normal schizogony was completed even in the presence of DFMO. Some reversal of the inhibition was achieved with cadaverine at high concentrations, while 1,3-diaminopropane and spermine failed to restore the development. Resumption of growth could be detected when putrescine was added even after 67 h of DFMO treatment. Electron microscopy did not reveal any changes in the morphology of parasites treated for 47 h, while 73 h of treatment with DFMO induced massive accumulation of pigment. Death was observed a few hours later. These results suggest that DFMO acts as a cytostatic rather than as a cytocidal agent. The four carbon diamine restored cell growth while the shorter or the longer homologous compounds showed little activity.

Animals↗
PubMed1987

Dorfman-Chanarin syndrome. A case report and a review.

Dorfman-Chanarin syndrome in two sisters of Jewish Iraqi origin is reported. This heritable disorder of the metabolism of neutral lipids was manifested by congenital ichthyosis, vacuoles in the leukocytes, and variable involvement of liver, muscle, central nervous system, and the auditory system. In two asymptomatic members of the family leukocyte vacuoles were found as the only sign of the syndrome. Clinical, pathologic, ultrastructural, and biochemical findings are described. Previous reported cases are reviewed.

Adult↗
PubMed1986

Primary inflammatory malignant fibrous histiocytoma of the colon.

A unique case of inflammatory malignant fibrous histiocytoma of the large bowel is presented. This lesion occurred in the colon of an elderly man suffering from weakness, anemia, anorexia, and weight loss. A right hemicolectomy was performed, and six months later, on follow-up, he was found to be well. The literature on visceral involvement by malignant fibrohistiocytic tumors is reviewed.

Aged↗
PubMed1986

Leishmania major: antileishmanial activity of methylbenzethonium chloride.

Methylbenzethonium chloride (MBCl) decreased the growth of Leishmania major promastigotes and amastigotes in vitro. This decrease occurred during 4 days of exposure to the drug at concentrations of 0.1 to 2.5 micrograms ml-1. MBCl at 2 micrograms ml-1 killed almost 100% of the free living promastigotes and 87% of amastigotes within 4 days of treatment. Electron microscopy studies showed marked swelling of mitochondria in treated parasites. A possible additional effect on the parasite surface membrane is discussed.

Benzethonium↗
PubMed1986

Studies on the effect of intralipid on human monocyte functions in vitro.

Intralipid (IL) particles were ingested by human monocytes in culture. These particles remained within the cells for periods of up to 3 weeks in culture. The presence of IL particles did not alter the normal secretion of lysozyme or prostaglandin E2 (PGE2), nor was the normal process of biochemical activation altered, as evidenced by the expected increase in PGE2 secretion and superoxide anion production by stimulated monocytes. Phagocytosis of zymosan particles was increased in monocytes that had ingested IL. These results indicate that in this in vitro system essential monocyte functions were not altered following ingestion of IL.

Dinoprostone↗
PubMed1984

Growth inhibition of Leishmania tropica amastigotes in vitro by rifampicin combined with amphotericin B.

Rifampicin and Amphotericin B (AMB) were studied separately and in combination to determine their effect in vitro on intracellular Leishmania tropica amastigotes. On the fourth day of treatment, rifampicin at 200 micrograms ml-1 or AMB at 0.15 microgram ml-1 reduced the parasites' survival index (PSI) to 10% compared with the untreated control. In combination, there was a significant synergistic effect at several concentrations. The synergistic therapeutic effects were not accompanied by toxicity to the host cells, although each drug alone caused cellular degeneration in the ultrastructure of the parasites with the formation of large autophagic-like vacuoles, while the combination increased the percentage of degenerate cells.

Amphotericin B↗
PubMed1984

Comparison of the effect of various stimuli on the leishmaniacidal capacity of human monocytes in vitro.

Leishmania organisms are obligate intracellular parasites of mammalian mononuclear phagocytes in vivo. In order to study the interactions of these parasites and mononuclear phagocytes, we have used a model of infection of Leishmania major in human monocytes in vitro. The presence of intracellular parasites did not alter the normal secretion of lysozyme or result in increased secretion of prostaglandin E2 (PGE2) or superoxide anion by the monocytes. Addition of concanavalin A (Con A), which binds to a specific membrane receptor, zymosan particles or endotoxin to infected monocyte monolayers, resulted in the expected increase in PGE2 secretion. In addition, the production of superoxide by infected monocytes treated with phorbol myristate acetate was not different from control uninfected cultures. Despite this evidence of biochemical activation, neither endotoxin, zymosan nor Con A had any parasiticidal effect on the intracellular parasites. In contrast, Con A-induced lymphokines from human mononuclear cells resulted in an increased killing of the intracellular amastigotes. These studies have shown that the induction of leishmaniacidal capacity of human monocytes is dependent on the type of stimulus used to induce activation.

Cells, Cultured↗