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Biomedical subjects

V Navarro

Publications and source records attributed to V Navarro.

At least 55 records · Page 3Linked to original sources
PubMed2000

In vitro characterization of radiolabeled monoclonal antibodies specific for the extracellular domain of prostate-specific membrane antigen.

Prostate-specific membrane antigen (PSMA) is a well-characterized cell surface antigen expressed by virtually all prostate cancers (PCas). PSMA has been successfully targeted in vivo with (111)In-labeled 7E11 monoclonal antibody (mAb; ProstaScint; Cytogen, Princeton, NJ), which binds to an intracellular epitope of PSMA. This work reports the in vitro characterization of three recently developed mAbs that bind the extracellular domain of PSMA (PSMAext). Murine mAbs J415, J533, J591, and 7E11 were radiolabeled with 131I and evaluated in competitive and saturation binding studies with substrates derived from LNCaP cells. J415 and J591 were conjugated to 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid labeled with (111)In. The uptake and cellular processing of these antibodies were evaluated in viable LNCaP cells. All four mAbs could be labeled with 131I up to a specific activity of 350 MBq/mg with no or little apparent loss of immunoreactivity. Competition assays revealed that J415 and J591 compete for binding to PSMAext antigen. J533 bound to a region close to the J591 binding epitope, but J533 did not interfere with J415 binding to PSMA. mAb 7E11 did not inhibit the binding of J415, J533, or J591 (or vice versa), consistent with earlier work that these latter mAbs bind PSMAext whereas 7E11 binds the intracellular domain of PSMA. Saturation binding studies demonstrated that J415 and J591 bound with a similar affinity (Kds 1.76 and 1.83 nM), whereas J533 had a lower affinity (Kd, 18 nM). In parallel studies, all four mAbs bound to a similar number of PSMA sites expressed by permeabilized cells (1,000,000-1,300,000 sites/cell). In parallel studies performed with viable LNCaP cells, J415, J533, and J591 bound to a similar number of PSMA sites (i.e., 600,000-800,000 sites/cell), whereas 7E11 bound only to a subpopulation of the available PSMA sites (95,000 sites/cell). This apparent binding of 7E11 to viable cells can be accounted for by a 5-7% subpopulation of permeabilized cells produced when the cells were trypsinized and suspended. Up to five DOTA chelates could be bound to either J415 or J591 without compromising immunoreactivity. A comparison of the cellular uptake and metabolic processing of the 131I- and (111)In-labeled antibodies showed a rapid elimination of 131I from the cell and a high retention of (111)In. All four mAbs recognized and bound to similar numbers of PSMAs expressed by ruptured LNCaP cells (i.e., the exposed intracellular and extracellular domains of PSMA). By comparison to J415 and J591, J533 had a lower binding affinity. Both J415 and J591 recognized and bound to the same high number of PSMAs expressed by intact LNCaP. By contrast, 7E11 bound to fewer sites expressed by intact LNCaP cells (i.e., the exposed extracellular domain of PSMA). Both J415 and J591 are promising mAbs for the targeting of viable PSMA-expressing tissue with diagnostic and therapeutic metallic radionuclides.

Antibodies, Monoclonal↗
PubMed2000

Analysis of the polymorphic (GT)(n) repeat at the dopamine beta-hydroxylase gene in Spanish patients affected by schizophrenia.

The presence of a polymorphic (GT)(n) repeat, a microsatellite repeat, at the human dopamine beta-hydroxylase (DBH) gene had been previously investigated in healthy people and in schizophrenic patients. The different DBH genotypes had been found to be associated to different DBH biochemical function, but no differences were found in the allelic and genotype frequencies between schizophrenic and control groups. To further clarify the potential involvement of the variation at the DBH gene in schizophrenia we have studied the DBH (GT)(n) repeat in a sample of 47 Spanish schizophrenic patients, in their healthy relatives (n = 72), and in a control population (n = 74). We have been able to identify five different variants of the DBH gene (A1, A2, A3, A4, A5) in the different groups. Subsequent statistical analysis revealed that the genotypes as well as the allele frequencies did not differ significantly among schizophrenic patients and the control population. Interestingly, the allelic variant A2 and the genotype A4/A2 were significantly more frequent in schizophrenic patients as compared with their healthy relatives. However, the association of the A2 allele with schizophrenia was not supported by the haplotype relative risk analysis of transmitted versus nontransmitted alleles. Therefore, although it will be important to extend the present analysis in a larger sample of schizophrenic patients and controls, our results suggest that the (GT)(n) does not seem to play a major role in the genetics of schizophrenia at least in this group of Spanish schizophrenic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:88-92, 2000.

Alleles↗
PubMed2000

Hepatitis C: a challenge for the generalist.

Most cases of hepatitis C become chronic, and although many of those remain silent for decades, some eventually progress to cirrhosis or other complications. Since almost 2% of the U.S. population is already infected, clinicians are likely to encounter growing numbers of patients with progressive disease. Treatment has been modified; ribavirin can now be added to interferon therapy.

Algorithms↗
PubMed2000

Seizure activity and safety in combined treatment with venlafaxine and ECT: a pilot study.

Some authors have described the combined use of ECT and psychotropic drugs, emphasizing possible interactions and synergisms of this combined therapy. We are unaware of reports of the concurrent use of the new antidepressant venlafaxine with ECT. The goals of our study were to assess the possible effects of venlafaxine on seizure length during ECT and the possible cardiovascular effects of this combined treatment. Nine severely ill, depressed patients were treated simultaneously with bilateral ECT and venlafaxine 150 mg/day and were compared with nine control, depressed subjects taking tricyclic antidepressants (TCA) and ECT. No patients had prolonged seizures and no spontaneous/tardive seizures outside ECT were observed. With regard to mean seizure length, no statistically significant differences were observed between the control group and the venlafaxine group. Neither significant increases in arterial blood pressure nor electrocardiographic recording abnormalities were found in venlafaxine patients when compared with the tricyclic group. Even though the small number of patients used is a significant limitation of this study, we found that combined venlafaxine and ECT appears to be safe when used in depression.

Adult↗
PubMed2000

Generalized cutaneous depigmentation following sulfamide-induced drug eruption.

A 41-year-old male developed a generalized drug eruption following sulfamide therapy, with progressive albino-like generalized cutaneous depigmentation. Electron microscopy showed the absence of melanocytes, and clear cells with Langerhans cell characteristics were seen along the basal layer. The present case constitutes a unique reaction to sulfamides not previously reported in the literature.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Facial superficial porokeratosis.

A case of exclusively facial superficial porokeratosis occurring in a young man is reported. These lesions were asymptomatic and remarkable because of their location. Histopathology revealed a typical superficial porokeratosis. Exclusively facial porokeratosis is an unusual clinical presentation. To our knowledge, it is the second report of a case with exclusively facial involvement.

Adolescent↗
PubMed2000

Development and quality of life: a critique of Amartya Sen's Development as freedom.

Presented here is a critical analysis of some of the major theses of Amartya Sen, as presented in his seminal work Development As Freedom. The author suggests that Sen's work, while representing a major break with the dominant neoliberal position reproduced in most national and international development agencies, is insufficient to explain the key relationship between freedom and development. The absence of an analysis of the power relations that cause and reproduce underdevelopment through national and international political institutions leaves Sen's work wanting. The author shows how Sen's interpretation of events and the conclusions derived from them, such as an explanation of famine in Bangladesh, are insufficient--when not faulty. The author also critically analyzes the United Nations Development Program reports, which, while documenting the nature and consequences of underdevelopment, barely touch on the political context in which underdevelopment occurs.

Communism↗
PubMed2000

The widening gap in death rates among income groups in the United States from 1967 to 1986.

Death rates in the United States have fallen since the 1960s, but improvements have not been shared equally by all groups. This study investigates the change in inequality in mortality by income level from 1967 to 1986. Comparable death rates are constructed for 1967 and 1986 using National Mortality Followback Surveys as numerators and National Health Interview Surveys as denominators. Direct age-adjusted death rates are calculated for income levels for the U.S. noninstitutionalized civilian population 35 to 64 years old. A summary measure of inequality in mortality adjusts for differences in the size and definition of income groups in the two years. In both 1967 and 1986, mortality decreased with each rise in income level. Measured in relative terms, this inverse relationship was greater in 1986 then in 1967 for men and women, blacks and whites. Between 1967 and 1986, death rates for those with maximal income declined between two and three times more rapidly than did rates for the middle and low income groups. The greatest increase in relative inequality was seen among white males.

Adult↗
PubMed2000

Are pro-welfare state and full-employment policies possible in the era of globalization?

There is a widely held belief in U.S. and European economic, political, and academic circles that economic globalization has considerably diminished states' power to follow public policies identified with the social democratic tradition, such as full-employment policies, comprehensive and universal provision of welfare state services, and state regulatory interventions in labor markets and economic policies. And large sectors of the European center-left and left parties believe that European monetary integration made expansionist and full-employment policies practically impossible, except when realized at the European continental level. This article presents empirical information that questions these positions. It documents how specific governments in Europe have been able to carry out such public policies during these years of economic globalization and monetary integration. Some countries (such as Sweden and Finland) that had carried out these policies then later weakened their implementation did so in response to political changes mostly unrelated to globalization of the economy or monetary integration. The article also analyzes and documents how countries that had followed expansionist and full-employment policies have responded to the globalization of financial markets.

Economics↗
PubMed2000

[Periodic hypokalemic paralysis as the manifestation of Graves' disease: clinical and electrophysiological study].

A 30-year-old Vietnamese man experienced severe weakness of four limbs revealing hypokalaemia. Tachycardia and goiter allowed to diagnose a Graves' disease. Thyrotoxic hypokaliemic periodic paralysis is a rare complication of hyperthyroidism in western populations. Electromyogram performed after resolution of the paralysis episodes revealed marked abnormalities of the muscular excitability. Duration of compound muscular action potential was markedly increased after a brief exercise. This increase might indicate a delayed repolarization of muscle fibres.

Adult↗
PubMed2000

[Fournier's gangrene. A study of 12 patients and a review].

We present the clinicoepidemiological and therapeutic characteristics of 12 patients with Fournier's gangrene. The mean age of the patients was 66 years and all had a known predisposing factor for the disease. In all cases there was a predominance of mixed flora (four Gram-positive cocci, nine Gram-negative bacilli and ten anaerobic pathogens), with only one case of bacteremia reported. Initial surgery was conducted and was complemented by antimicrobial administration (imipenem, cefotaxime, clindamycin, penicillin and gentamicin alone and in combination) and local treatment with sugar and povidone-iodine. Hyperbaric oxygen was not used in any cases. At the end of treatment a mesh graft could be applied in 11 patients, all of whom showed an excellent functional and aesthetic recovery. The mean time of hospital stay was lengthy (49 days). The good evolution of the lesions after starting the local treatments with the sugar povidone-iodine combination should be emphasized.

Administration, Topical↗
PubMed1999

Contulakin-G, an O-glycosylated invertebrate neurotensin.

We have purified contulakin-G, a 16-amino acid O-linked glycopeptide (pGlu-Ser-Glu-Glu-Gly-Gly-Ser-Asn-Ala-Thr-Lys-Lys-Pro-Tyr-Ile-Leu-OH, pGlu is pyroglutamate) from Conus geographus venom. The major glycosylated form of contulakin-G was found to incorporate the disaccharide beta-D-Galp-(1-->3)-alpha-D-GalpNAc-(1-->) attached to Thr10. The C-terminal sequence of contulakin-G shows a high degree of similarity to the neurotensin family of peptides. Synthetic peptide replicates of Gal(beta-->3) GalNAc(alpha-->)Thr10 contulakin-G and its nonglycosylated analog were prepared using an Fmoc (9-fluorenylmethoxycarbonyl) protected solid phase synthesis strategy. The synthetic glycosylated con- tulakin-G, when administered intracerebroventricular into mice, was found to result in motor control-associated dysfunction observed for the native peptide. Contulakín-G was found to be active at 10-fold lower doses than the nonglycosylated Thr10 contulakin-G analog. The binding affinities of contulakin-G and the nonglycosylated Thr10 contulakin-G for a number of neurotensin receptor types including the human neurotensin type 1 receptor (hNTR1), the rat neurotensin type 1 and type 2 receptors, and the mouse neurotensin type 3 receptor were determined. The binding affinity of the nonglycosylated Thr10 contulakin-G was approximately an order of magnitude lower than that of neurotensin1-13 for all the receptor types tested. In contrast, the glycosylated form of contulakin-G exhibited significantly weaker binding affinity for all of the receptors tested. However, both contulakin-G and nonglycosylated Thr10 contulakin-G were found to be potent agonists of rat neurotensin receptor type 1. Based on these results, we conclude that O-linked glycosylation appears to be a highly unusual strategy for increasing the efficacy of toxins directed against neurotransmitter receptors.

Amino Acid Sequence↗
PubMed1999

Two antimicrobial alkaloids from Bocconia arborea.

Two alkaloid constituents of Bocconia arborea showed considerable antimicrobial activity against gram-positive and gram-negative bacteria and Candida albicans. Bioactivity-guided fractionation with thin-layer bioautography led to the isolation of the two known benzophenanthridine alkaloids, dihydrochelerythrine and dihydrosanguinarine. The minimal inhibitory concentration was determined for each compound using a twofold serial dilution assay. The structures of these compounds were determined by 1H and 13C NMR analyses.

Alkaloids↗