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Biomedical subjects

S Levi

Publications and source records attributed to S Levi.

At least 109 records · Page 6Linked to original sources
PubMed1990

Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing.

To find out whether non-steroidial anti-inflammatory drugs (NSAIDs) inhibit the proliferation of mucosal cells that normally leads to healing of gastric ulcers a microdissection technique was used to quantify mitosis in gastric glands at the ulcer edge in relation to that in the adjacent mucosa. The regeneration index thus obtained of the ulcer edge was greater in the 9 subjects with gastric ulcers not taking NSAIDs (mean index 3.1 [SEM 0.61]) than that in the 8 patients taking NSAIDs (index 1.49 [0.16]). In rats in which gastric ulcers were produced with a cryoprobe, the ulcers were larger and slower to heal in those receiving indomethacin than in controls; also, immunohistochemical staining indicated significantly fewer mitotic cells in glands adjacent to the ulcer in indomethacin-treated rats (8 mitoses [SEM 3]) than in control animals (25 [5]). The prostaglandin E1 analogue misoprostol reversed the inhibition of healing and substantially restored the proliferative rate in the animals. Inhibition of epithelial cell division normally involved in gastric ulcer healing would contribute to the high prevalence of gastric ulcer during NSAID therapy.

Adult↗
PubMed1990

A mutational analysis of the epitopes of recombinant human H-ferritin.

Murine monoclonal antibodies were elicited by the recombinant human H-ferritin overexpressed in Escherichia coli. They had a specificity analogous to that of the antibodies elicited by natural human H-chain, and all of them showed low additivity in binding the recombinant ferritin. Four antibodies of each group were challenged with four H-ferritin mutants overexpressed in E. coli, altered in different accessible areas of the molecule. They consisted of deletions of the first 13 and last 22 amino acids, a duplication of an 18 amino acid sequence in the loop region, and a substitution of a 5 amino acid stretch in the three-fold symmetry axis region. Double diffusion, immunodot analyses and inhibition plots indicated that: (1) all the mutants were recognized by at least one antibody; (2) the deletion of the N-terminus and the duplication in the loop region had the strongest effect on antibody binding; and (3) epitope boundaries of the various antibodies could not be recognized. The antibodies were tested with H-containing ferritins from rat and hen hearts, and showed low or absent reactivities despite their high structural homology with human ferritin. Comparison of the amino acid sequences of human, mouse, rat and hen H-chains, together with mutational data, suggested that; (i) ferritin epitopes are large, probably encompassing a large portion of the subunit surface and (ii) Thr-5 and Cys-90 have a role in H-ferritin immunogenicity.

Amino Acid Sequence↗
PubMed1990

Pharmacological characterization of polycation-induced rat hind-paw oedema.

1. The inflammatory response induced by poly-L-arginine in the rat hind-paw was studied both by measuring paw oedema and histologically. 2. The paw volume was measured with a hydroplethysmometer at 0.5, 1, 2, 4, 6 and 18 h after the subplantar injection of the polycation. Protein extravasation was evaluated with Evans' blue and the histology studied by light microscopy. 3. Poly-L-arginine (12, 24, 43 and 115kD) caused dose- and molecular weight-dependent oedema which had a rapid onset and long duration. Evans' blue extravasation paralleled the oedema induced by poly-L-arginine. Microscopic examination of the paws at early stages of oedema formation showed exuberant liquid exudate with no inflammatory cells. After 18 h, a cellular infiltrate was present, consisting mainly of mononuclear cells. 4. Indomethacin, dexamethasone, BW755c or the PAF-antagonist WEB 2086 caused no significant inhibition of the poly-L-arginine-induced oedema. Cyproheptadine had inhibitory effects only on the early stages of the polycation-induced oedema. Similar results were observed with rats depleted of histamine and 5-hydroxytryptamine. 5. Heparin, a polyanion, injected in the rat paw caused a marked inhibition of the polycation-induced oedema. NG-monomethyl-L-arginine (LNMMA), an inhibitor of EDRF synthesis, injected locally also produced a marked inhibition, but this inhibition was reversed by iloprost. 6. These results suggest that the oedema induced by polycations was due to their cationic charge. The inhibitory effect of LNMMA is probably due to a decrease in vascular flow rather than a decrease in vascular permeability.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1990

Tarsometatarsal involvement in juvenile spondyloarthropathy.

Patients with juvenile spondyloarthropathy who carry HLA B27 antigen or have a family history of ankylosing spondylitis may have marked tarsometatarsal arthritis. This may be associated with hindfoot involvement and result in a supination deformity. Spontaneous fusion with complete obliteration of the tarsometatarsal joints may occur.

Adolescent↗
PubMed1990

"Diaphragm-like" strictures of the small bowel in patients treated with non-steroidal anti-inflammatory drugs.

The radiological findings are described in four patients who developed strictures of the small bowel, and who had received non-steroidal, anti-inflammatory drugs (NSAIDs) for 1.5-15 years. Clinical presentation was that of subacute small bowel obstruction. Small bowel barium studies showed multiple discrete strictures. Some strictures were indistinguishable from those of regional enteritis. Others however were narrow "diaphragm-like" septae encroaching on and markedly narrowing the ileal lumen, and shown histologically to be due to submucosal fibrosis. It is suggested that these strictures are likely to be consequent on NSAIDs administration and that radiologists and surgeons need to be aware of these "diaphragms" which can be very difficult to detect on barium examination, either small bowel follow-through or enteroclysis, and at laparotomy.

Adult↗
PubMed1989

Mutational analysis of the channel and loop sequences of human ferritin H-chain.

Human ferritin H-chain mutants were obtained by engineering the recombinant protein expressed by Escherichia coli. The mutagenesis were directed to the C-terminal sequence forming the hydrophobic channel, to the hydrophilic channel and to the loop sequence. The mutants were analysed for extent of expression, for stability, for capacity to incorporate iron and for kinetics of iron uptake and iron oxidation. Of the 22 mutants analysed only two with deletions of single residues in the loop sequence and one with deletion of the last 28 amino acid residues did not assemble into ferritin-like proteins. The other mutants assembled correctly and showed similar chemical/physical properties to the wild-type; they included duplication of an 18-amino acid-residue stretch, deletion of the last 22 and the last seven residues and various mutations of single amino acid residues. Two mutants with extensive alteration in the C-terminal sequence had a diminished thermostability associated with incapability to incorporate iron though they still catalysed iron oxidation. The mutants with alterations of the sequence around the hydrophilic channel showed diminished iron uptake and oxidation kinetics, together with a slightly larger apparent molecular size. The results indicate (i) that two of the sequences are important for ferritin assembly/stability, (ii) that the presence of the hydrophobic channel is essential for formation of the iron core and (iii) that the sites of iron interaction and the path of iron penetration into ferritin remain unidentified.

Chromosome Deletion↗
PubMed1989

Development of an immunoassay for all human isoferritins, and its application to serum ferritin evaluation.

Calibrated mixtures of anti-H and anti-L ferritin subunit monoclonal antibodies were used in a sandwich enzyme-immunoassay for the evaluation of all isoferritins. The assay was designed to have overlapping calibration plots for human liver (95% L-chain) and recombinant human H-chain ferritin (100% H-chain). It appeared to recognize all the heart isoferritins including the ones in the middle of the isoferritin spectrum. By direct comparison it was shown that these isoferritins are under-evaluated by the assays for H- and L-subunit-rich ferritins, based on the two separated antibodies. The three assays (for total, H-rich and L-rich ferritins) provide an index of the presence of the isoferritins with intermediate H/L composition. Sera from 30 tumor and non-tumor patients were analyzed. Intermediate isoferritins were found in 2 non-tumor subjects and in none of the 14 patients with Hodgkin's disease or mammary carcinoma. It is concluded that the evaluation of the total and intermediate isoferritins is possible, but does not have an evident clinical significance for tumor monitoring.

Adult↗
PubMed1989

Identification of the ferroxidase centre in ferritin.

Ferroxidase activity in human H-chain ferritin has been studied with the aid of site-directed mutagenesis. A site discovered by X-ray crystallography has now been identified as the ferroxidase centre. This centre is present only in H-chains and is located within the four-helix bundle of the chain fold.

Animals↗
PubMed1989

Expression and structural and functional properties of human ferritin L-chain from Escherichia coli.

The human ferritin L-chain cDNA was cloned into a vector for overproduction in Escherichia coli, under the regulation of a lambda promoter. The plasmid obtained contains the full L-chain coding region modified at the first two codons. It is able to direct the synthesis of the L-chain which can constitute up to 15% of the total soluble protein of bacterial extract. The L-chains assemble to form a ferritin homopolymer with electrophoretic mobility, molecular weight, thermal stability, spectroscopic, and immunological properties analogous to natural ferritin from human liver (95% L-chain). This recombinant L-ferritin is able to incorporate and retain iron in solution at physiological pH values. At variance with the H-ferritin, the L form does not uptake iron at acidic pH values and does not show detectable ferroxidase activity. It is concluded that ferritin L-chain lacks the ferroxidase site present in the H-chain and that the two chains may have specialized functions in intracellular iron metabolism.

Blotting, Western↗
PubMed1989

Campylobacter pylori and duodenal ulcers: the gastrin link.

The possibility that Campylobacter pylori (CP) in the gastric antrum stimulates gastrin release in duodenal ulcer (DU) disease was examined in 31 patients. The 25 patients with antral colonisation with CP had higher basal and meal-stimulated plasma gastrin concentrations, and higher peak acid output (PAO), than did the 6 without CP in the autumn.

Adult↗