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Biomedical subjects

S Cruz

Publications and source records attributed to S Cruz.

At least 19 recordsLinked to original sources

Laryngotracheal reconstruction in subglottic stenosis: an ancient problem still present.

BACKGROUND: Subglottic stenosis is an ancient but persistent problem as a cause of airway obstruction. The etiology and the results of surgical treatment with thyrotracheal anastomosis were reviewed. METHODS: Fifty-six patients with subglottic stenosis were studied. All were subjected to laryngotracheal reconstruction by thyrotracheal anastomosis with partial resection of the cricoid. RESULTS: Of all 56 cases of subglottic stenosis, 48 (86%) had history of previous tracheal intubation, and only 8 (14%) had different non-neoplastic obstructive processes such as scleroma, direct injury, hamartoma, and amyloidosis. Immediate results were good in all cases. After 1 year follow-up, results of thyrotracheal anastomosis were successful in 44 (91%). In 4 other cases a restenosis was observed. Eight patients were lost to follow-up. CONCLUSIONS: Subglottic stenosis is still frequent after tracheal intubation, but other causes must be considered. Laryngotracheal reconstruction with thyrotracheal anastomosis with partial cricoid resection was feasible with good results in 91% of the cases with follow-up, but this procedure must be performed by a skilled surgical team.

Adult↗

Mapping of monoclonal antibodies specific to P64k: a common antigen of several isolates of Neisseria meningitidis.

P64k is a minor outer membrane protein from Neisseria meningitidis. This protein has been produced at high levels in Escherichia coli. We generated a group of monoclonal antibodies (mAbs) against recombinant P64k, which recognise four non-overlapping epitopes, as shown using competition assays with biotinylated mAbs. The P64k sequences involved in mAbs binding were mapped with synthetic overlapping peptides derived from the P64k protein, and located in the previously determined three-dimensional structure of the protein. These antibodies were also characterised by whole-cell ELISA and bactericidal tests against N. meningitidis. Only two of the recognised epitopes were exposed on the bacterial surface, and none of the mAbs showed bactericidal activity. The relationship between these results and the structural data on the epitopes bound by the mAbs is discussed.

Amino Acid Sequence↗

A bacterial single-chain Fv antibody fragment that inhibits binding of its parental anti-E-selectin monoclonal antibody to activated human endothelial cells.

Using the polymerase chain reaction, we cloned, modified, and linked antibody variable (V) region coding genes from a mouse hybridoma, and produced a bacterial single-chain Fv (scFv) antibody fragment specific for E-Selectin. A vector of pBR322 origin, bearing the tryptophan promoter and the ompA bacterial signal peptide, was used to direct scFv expression to periplasm. The vector included a six-histidine coding sequence 5' to the scFv for the purification of the expressed protein using immobilized metal affinity chromatography (IMAC). We found that the VH-Linker-VL 32-33 kDa scFv remained insoluble after cellular fractionation, and transmission electron microscopy showed the new protein to be present in the periplasm as inclusion bodies. The scFv was solubilized using urea, purified using IMAC, and renatured to its active form. In a competitive enzyme-linked immunosorbent assay with activated human vein endothelial cells in the solid phase, the scFv competed for binding with the original monoclonal antibody.

Amino Acid Sequence↗

Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by gamma-radiolysis of ethanol-water mixtures.

Oxidized low density lipoproteins (LDL) are believed to play a central role in the events that initiate atherosclerosis. Antioxidants have been shown to decrease the oxidation of LDL, leading to the diminution of atherosclerosis. Since it is well-known that decreased levels of dehydroepiandrosterone (DHEA) are linked to the development of atherosclerosis, we studied the modulation of the oxidation of LDL by DHEA. LDL were obtained from 10 healthy subjects and oxidized by free radicals produced by gamma-radiolysis of ethanol-water mixtures. The formation of conjugated dienes and thiobarbituric acid-reactive substances (TBARS), the vitamin E content, as well as the incorporation of 4-[14C]DHEA in LDL and the chemotactic effect of oxidized LDL in the presence of DHEA towards monocytes, were investigated. It was found that DHEA was able to inhibit the oxidation of LDL by reducing over 90% of the conjugated dienes and TBARS formation, as well as by reducing the vitamin E disappearance and significantly decreasing the chemotactic activity towards monocytes. Our results suggest that DHEA exerts its antioxidative effect by protecting the endogenous vitamin E of LDL.

Adult↗

Clinical and electrophysiological phenotype of a homozygously duplicated Charcot-Marie-Tooth (type 1A) disease.

Type 1A of Charcot-Marie-Tooth disease (CMT1A) is associated with a microduplication of chromosome 17 (region 17p11.2) which contains PMP22, an important gene for peripheral nerve myelination. Patients carrying two duplications are expected to have a more severe phenotype, close to the Dejerine-Sottas syndrome. In this article, we report a family of 5 CMT1A patients in whom the unrelated father and mother carry a 17p11.2 duplication. The 2 daughters carry only one duplication (one given by the father, the other given by the mother), but the son carries two 17p11.2 duplications. Interestingly, the clinical phenotype of the son is more severe (scoliosis) compared to those of his sisters, but his motor nerve conduction velocities are in the range of a heterozygote CMT1A patient. The mechanisms leading to a more severe phenotype for CMT1A are discussed and may not be strictly related to lower nerve conduction velocities.

Adult↗

Smooth muscle relaxing compounds from Dodonaea viscosa.

Bioassay-directed fractionation of the chloroform-methanol (1:1) extract of Dodonaea viscosa (L.) Jacq. (Sapindaceae) resulted in the isolation of four active spasmolytic principles: sakuranetin (1), 6-hydroxykaempferyl 3,7-dimethyl ether (2) hautrivaic acid (3), and ent-15, 16-epoxy-9 alpha H-labda-13(16)14-diene-3 beta, 8 alpha-diol (4). All the isolated compounds elicited a concentration-dependent inhibition of the spontaneous and electrically-induced contractions of guinea-pig ileum. Sakuranetin and the ent-labdane inhibited ileum contractions evoked by acetylcholine (Ach), histamine, and barium chloride. In addition, both substances were capable of relaxing contractions of rat uterus induced by Ca2+ in K(+)-depolarizing solution, displacing to the right the concentration-response curves to Ca2+. These results suggest that sakuranetin and ent-15,16-epoxy-9 alpha H-labda-13(16)14-diene-3 beta, 8 alpha-diol produce an interference with calcium metabolism in smooth muscle cells. The spasmolytic activity exhibited by the active principles from D. viscosa, provides the pharmacological basis for the traditional use of the plant as an antispasmodic agent.

Animals↗

Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development.

Basic fibroblast growth factor (bFGF) has shown a neurotrophic effect in the neurons of several CNS areas. In vivo, it contributes to restore neurochemical and morphological deficits in different rodent models of brain damage, including rats with brain damage induced by hypoxia/ischemia when FGF was intramuscularly (i.m.) administered. Toxicological and immunological studies performed in rats, mice and volunteers showed no evidence of side-effects. Bovine FGF was i.m. administered in children with mental retardation caused by perinatal hypoxia, aged 1-15 years, at dosages of 0.4 or 0.28 microgram kg-1, once or twice a month, over 7-12 months. Group A [n = 12; 6 treated (T), 6 controls (Ct)], group B (n = 16; 8 T, 8 Ct) and group C (n = 67; 45 T, 22 Ct) were evaluated with the P. A. R. scale, the WISC-RM and the Gesell scale, respectively. Development increased significantly in treated children from groups A (P < 0.02) and C (P < 0.001), and IQ rose by more than 10 points (P < 0.001) in group B patients.

Adolescent↗

Human monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many pathogenic strains of Neisseria meningitidis.

Neisseria meningitidis is a causative agent of meningitis. Despite vaccination programs, it still causes a large number of deaths in young children. Early diagnosis followed by passive immunization with human monoclonal antibodies could be an approach to effective therapy. Peripheral blood lymphocytes from normal, healthy blood donors and from vaccinated individuals were immunized in vitro, using outer membrane proteins purified from N. meningitidis B:4:P1.15. The immunized human B cells were Epstein-Barr virus transformed and fused to a heteromyeloma. Several stable human hybridoma cell lines were established and two, secreting antibodies against the 31-kDa class 5c outer membrane protein, were characterized further. The human antibodies were of IgG1 and IgG3 isotypes, with kappa light chains. The recognized epitope was commonly found among pathogenic strains of N. meningitidis; thus, these human monoclonal antibodies may be important in the evaluation of N. meningitidis infections.

Animals↗

Lack of toxicity of intravitreally administered interferon alpha-2a.

We investigated the toxicity of single doses of intravitreally administered interferon alpha-2a in albino rabbits. Following injection of interferon in doses of 40,000, 80,000, 160,000, 320,000, and 640,000 IU/0.1 mL, no significant histologic changes were detected by light and electron microscopy. Photopic and scotopic electroretinography showed no alteration of retinal function.

Animals↗

Itraconazole in the treatment of coccidioidomycosis.

Sixteen patients with coccidioidomycosis were treated with itraconazole for one year. Sixteen suffered from pulmonary coccidioidomycosis, two of them had associated mediastinal lesions, and one suffered from skin coccidioidomycosis. The daily dose used was 400 mg during the one-year period. Patients were clinically evaluated every month and tested for mycosis every three months. All patients except for one showed negative cultures on the third month after treatment began. Effectiveness achieved was excellent in eight patients (50 percent); a very good response was found in seven patients (44 percent); no response was seen in one patient (6 percent). There were four (25 percent) relapses and one dropout. Side effects seen were high blood pressure (19 percent) and lower limb edema (6 percent), which was temporary and at no time required discontinuing the drug therapy. We believe that itraconazole is an effective drug to treat coccidioidomycosis with a wide safety margin. It is well tolerated, and the incidence of relapses was low.

Adult↗

Long-acting contraceptive agents: esters of norethisterone with alpha- and/or beta-chain branching.

The synthesis of eighteen esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) is described. These all possess some form of alpha- and/or beta-substitution in the ester side-chain. The work was undertaken in order to evaluate any long-acting fertility control effect intrinsic in such compounds. A pentamethyl disiloxy ether was also included in the group of substances prepared for testing because of its similar substitution pattern.

Esters↗