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Biomedical subjects

A Marra

Publications and source records attributed to A Marra.

At least 55 records · Page 3Linked to original sources

Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages.

The legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular parasite. Its interaction with phagocytes has characteristics in common with several other intracellular parasites. Critical aspects of L. pneumophila intracellular multiplication are evasion of lysosomal host cell defenses and the presence of a nutritionally appropriate environment. Following phagocytosis, wild-type L. pneumophila multiply within a specialized phagosome which does not fuse with secondary lysosomes. Mutants which have lost the ability to grow within phagocytes no longer cause disease in animals, indicating that the capacity to multiply intracellularly is important for pathogenesis. One such mutant, 25D, has been shown to be defective in inhibiting phagosome-lysosome fusion. This phagolysosomal environment is not conducive to Legionella growth. We report the isolation of a region of the L. pneumophila genome (icm, intracellular multiplication) which restores the capacity of 25D to multiply in human macrophages. The complemented mutants also regain the capacity to interfere with phagosome-lysosome fusion and to cause lethal pneumonia in guinea pigs.

Animals↗

[Hypertrophy of the masseter: a rare case associated with hypertrophic cardiomyopathy].

Masseteric hypertrophy is a rare, monolateral or bilateral lesion. The aetiology is often unknown and both congenital and acquired forms are reported in the literature. The authors report a case of masseteric hypertrophy associated with hypertrophic cardiomyopathy. Family history shows two brothers suffering from the same cardiac disease. Echography, computed tomography, EMG test and aspiration biopsy of masseteric muscle were performed. Echocardiography and HLA, B and C antigens of 16 relatives were also performed. In the report case the authors hypothesized a multifactorial background on a genetic basis.

Adult↗

Endobronchial administration of iodine-131 B72.3 monoclonal antibody in patients with lung cancer.

We tested the feasibility of endobronchial administration of radiolabelled monoclonal antibodies (MoAbs) and the biodistribution of the radiotracer. Ten patients with histological confirmed adenocarcinoma or squamous cell carcinoma were studied. Nine received 470 muCi (103 micrograms) of Iodine-131-B72.3, a monoclonal antibody reacting against TAG 72 antigen, while one patient received 502 muCi (291 micrograms) of 131I-4C4, an indifferent antibody used for comparison in a negative control study. The radiolabelled antibody was administered through a flexible fiberoptic bronchoscope and placed on the tumour mass under visual monitoring. Scans with a large field-of-view gamma-camera showed retention of 131I-B72.3 at the tumour site up to 6-9 days in six of eight patients. No other organs were visualized with the exception of faint activity in the gastrointestinal tract, bladder and thyroid. On the contrary, the indifferent antibody 131I-4C4 was not retained at the tumour site 6 days after MoAb administration, and more prominent activity was found in the gastrointestinal tract. In one patient the study was not technically adequate because of failure of the delivery system. The vascular compartment contained less than 3% of the administered dose. We conclude that endobronchial administration is a feasible technique and allows stable and specific targetting of bronchial tumours. Furthermore, the low activity found in the plasma and other organs suggests that this approach may be used to deliver therapeutic doses of MoAbs to lung cancers.

Adenocarcinoma↗

Rhizobium meliloti exopolysaccharides: genetic analyses and symbiotic importance.

Genetic experiments have indicated that succinoglycan (EPS I), the acidic Calcofluor-binding exopolysaccharide, of the nitrogen-fixing bacterium Rhizobium meliloti strain Rm1021 is required for nodule invasion and possibly for later events in nodule development on alfalfa and other hosts. Fourteen exo loci on the second megaplasmid have been identified that are required for, or affect, the synthesis of EPS I. Mutations in certain of these loci completely abolish the production of EPS I and result in mutants that form empty Fix- nodules. We have identified two loci, exoR and exoS, that are involved in the regulation of EPS I synthesis in the free-living state. Certain exo mutations which completely abolish EPS I production are lethal in an exoR95 or exoS96 background. Histochemical analyses of the expression of exo genes during nodulation using exo::TnphoA fusions have indicated that the exo genes are expressed most strongly in the invasion zone. In addition, we have discovered that R. meliloti has a latent capacity to synthesize a second exopolysaccharide (EPS II) that can substitute for the role(s) of EPS I in nodulation of alfalfa but not of other hosts. Possible roles for exopolysaccharides in symbiosis are discussed.

Genes, Bacterial↗

N-p-methoxybenzylidene derivatives of 2-amino-2-deoxy-D-glucose as glycosyl donors: a reinvestigation.

6-O-Acetyl-3,4-di-O-benzyl-2-deoxy-2-p-methoxybenzylideneamino-D- glucopyranosyl chloride, 3,4,6-tri-O-acetyl-2-deoxy-2-p-methoxybenzylideneamino-alpha-D-glu copyranosyl bromide, 3,4,6-tri-O-acetyl-2-deoxy-2-p-methoxybenzylideneamino-alpha- and -beta-D- glucopyranosyl trichloroacetimidate, and 3,4,6-tri-O-acetyl-2-deoxy-2-p-nitrobenzylideneamino-alpha-D-gluco pyranosyl bromide have been synthesised, and their behaviour as glycosylation agents with various soluble promoters has been investigated. The results obtained question the accepted non-participating character of the N-p-methoxybenzylideneamino group.

Benzylidene Compounds↗

The HL-60 model for the interaction of human macrophages with the Legionnaires' disease bacterium.

The facultative intracellular pathogen, Legionella pneumophila, multiplies within and kills human monocytes and alveolar macrophages. We show that L. pneumophila strain Philadelphia-1 infects, multiplies within and kills the promyelocyte HL-60 cell line after its differentiation into macrophage-like cells. The characteristics of the interaction between L. pneumophila and differentiated HL-60 cells closely resemble those between L. pneumophila and human peripheral blood monocytes. With both cell types, C receptors and serum C mediate attachment of L. pneumophila, which are taken up by coiling phagocytosis. The replicative phagosome is lined with ribosomes; intracellular multiplication is iron-dependent; and replicating bacteria ultimately destroy the host cell. As in human monocytes, an avirulent mutant derivative of L. pneumophila Philadelphia-1, 25D, does not replicate in and is not cytopathic for differentiated HL-60 cells. Differentiated HL-60 cells therefore provide a convenient and faithful model for the study of L. pneumophila-mononuclear phagocyte interaction.

Bacterial Adhesion↗

Synthesis of disaccharide fragments of dermatan sulfate.

Condensation of crystalline methyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D-galactopyranoside with methyl (2,3,4-tri-O-acetyl-alpha-L-idopyranosyl bromide)uronate in dichloromethane, in the presence of silver triflate and molecular sieve, provided 54% of methyl 2-azido-4,6-O-benzylidene-2-deoxy-3-O-(methyl 2,3,4-tri-O-acetyl-alpha-L-idopyranosyluronate)-beta-D-galactopyranoside . The use of methyl (2,3,4-tri-O-acetyl-alpha-L-idopyranosyl trichloroacetimidate)uronate as glycosyl donor, in the presence of trimethylsilyl triflate, improved the yield to 68%. Regioselective opening of the benzylidene group with sodium cyanoborohydride followed successively by O-sulfation with the sulfur trioxide-trimethylamine complex, saponification, catalytic hydrogenolysis and selective N-acetylation gave the disodium salt of methyl 2-acetamido-2-deoxy-3-O-(alpha-L-idopyranosyluronic acid)-4-O-sulfo-beta-D-galactopyranoside. Condensation of methyl 2-azido-4,6-O-benzylidene-2-deoxy-beta-D-galactopyranoside with methyl (2,3,4-tri-O-acetyl-alpha-D-glucopyranosyl bromide)uronate in dichloromethane, in the presence of silver triflate and molecular sieve, gave methyl 2-azido-4,6-O-benzylidene-2-deoxy-3-O-(methyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosyluronate)-beta-D-galactopryano side in 85% yield. The sequence already described then gave the disodium salt of methyl 2-acetamido-2-deoxy-3-O-(beta-D-glucopyranosyluronic acid)-4-O-sulfo-beta-D-galactopyranoside.

Carbohydrate Sequence↗

Isolation of a Legionella pneumophila restriction mutant with increased ability to act as a recipient in heterospecific matings.

The ability of Legionella pneumophila to act as a recipient of IncP and IncQ plasmids in matings with Escherichia coli varies widely from strain to strain. We found that the low efficiency of mating of the Philadelphia-1 strain is due to a type II restriction-modification system, and we isolated and characterized a Philadelphia-1 mutant that lacks the restriction enzyme activity.

Conjugation, Genetic↗

[9 cases of early gastric cancer disclosed on chronic ulcer with or without complications].

The authors report their experience on 9 cases of early gastric cancer developed on a peptic ulcer border. They outline the paradoxical providence of the complications (hemorrhage and perforation) leading to cancer recognition as a focus in the benign ulcer. Therapeutic management of the occasionally discovered cancer on the peptic ulcer border is also discussed.

Aged↗

Translocation X;13 in a patient with retinoblastoma.

We describe the clinical and cytogenetic findings in a child with retinoblastoma and a translocation between chromosomes X and 13. The X;13 translocation in this patient does not involve band 13q14, the assigned locus for retinoblastoma.

Chromosome Banding↗

Synchronous and metachronous cancer of the stomach.

In the last 10 years 407 cancers of the stomach were observed at the 1st Department of Surgery of the University of Bologna. 248 were subjected to curative resection (59 were Early Gastric Cancers and 189 were Advanced Gastric Cancers). Among them 14 gastric cancers with multiple foci (synchronous cancers) and 7 cancers of the gastric stump (metachronous cancers) were found in the same period. Each lesion was histologically proved and a tract of normal mucosa was found between two cancers both macroscopically and microscopically. The frequency of primary multiple tumoural foci was higher for early Gastric Cancer (E.G.C.) in comparison with Advanced Gastric Cancer (A.G.C.), being 8.4% for the former and 4.7% for the latter.

Adenocarcinoma↗

Chemical synthesis of the desialylated human Cad-anti-genic determinant.

Benzyl 2-azido-2-deoxy-beta-D-galactopyranoside was converted into benzyl 2-azido-4,6-O-benzyl-2-deoxy-beta-D-galactopyranoside via benzylidenation, p-methoxybenzylation, acid hydrolysis, benzylation, and selective oxidation. Condensation of 1,2,3,4,6-penta-O-acetyl-beta-D-galactopyranose with benzyl 2-azido-4,6-di-O-benzyl-2-deoxy-beta-D-galactopyranoside in the presence of trimethylsilyl triflate gave crystalline benzyl 2-azido-4,6-di-O-benzyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-beta-D-ga lactopyranosyl)-beta-D-galactopyranoside (76%), which was converted into benzyl 2-azido-4,6-di-O-benzyl-2-deoxy-3-O-(2,6-di-O-benzyl-beta-D-galactopy ranosyl)-beta-D-galactopyranoside and condensed with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha-D-galactopyranosyl bromide in the presence of silver silicate on alumina and molecular sieve 4 A to give 61% of benzyl O-(3,4,6-tri-O-acetyl-2-azido-2-deoxy-beta-D-galactopyranosyl)-(1----4)- O-(2,6-di- O-benzyl-beta-D-galactopyranosyl)-(1----3)-2-azido-4,6-di-O-benzyl-2-deo xy- beta-D-galactopyranoside. Reduction with sodium borohydride followed by N-acetylation, O-deacetylation, and catalytic hydrogenolysis then gave O-(2-acetamido-2-deoxy-beta-D-galactopyranosyl)-(1----4)-O-beta-D-gal actopyranosyl-(1----3)-2-acetamido-2-deoxy-D-galactopyranose, the desialylated human Cad-antigenic determinant.

Carbohydrate Conformation↗