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Biomedical subjects

E Silva

Publications and source records attributed to E Silva.

At least 73 records · Page 4Linked to original sources

Apoptosis induction in nonirradiated human HL-60 and murine NSO/2 tumor cells by photoproducts of indole-3-acetic acid and riboflavin.

The effect of the photoproducts of indole-3-acetic acid sensitized by riboflavin on nonirradiated human HL-60 and murine NSO/2 tumor cells was studied. Severe damage with a dose-response effect was observed on both cell types. The effect was greater than that previously described for the tryptophan riboflavin photoproducts. Electron microscopy studies and flow cytometry analysis of DNA fragmentation allowed us to conclude that the photoproducts studied in this work induce cell death by an apoptotic mechanism.

Animals↗

Physical and transcriptional analysis of the Trypanosoma brucei genome reveals a typical eukaryotic arrangement with close interspersionof RNA polymerase II- and III-transcribed genes.

To further our understanding of the structural and functional organization of the Trypanosoma brucei genome, we have searched for and analyzed sites in the genome where Pol II transcription units meet Pol III genes. Physical and transcriptional maps of cosmid clones spanning the Pol III-transcribed U2 small nuclear RNA (snRNA) and U3 snRNA/7SL RNA gene loci demonstrated that single-copy Pol II genes are closely associated with Pol III-transcribed genes, being separated from each other by 0.6-3 kb. At the U3/7SL transcriptional domain, two Pol II transcription units converged from either side of the chromosome towards the Pol III genes, suggesting that at least for the chromosome containing the U3 snRNA and 7SL RNA genes, there exist two distinct initiation sites for Pol II. Furthermore, in all cases the Pol III genes hallmark the end of Pol II transcription units, suggesting perhaps a functional role for this genetic arrangement. Lastly, we asked whether the environment within a Pol III transcriptional domain allowed expression of pre-mRNA. To test this we inserted a CAT gene cassette, seemingly promoterless but endowed with pre-mRNA processing signals, in the chromosome between the U3 snRNA and 7SL RNA genes. Interestingly, abundant CAT mRNA was produced suggesting that the Pol III genes in the immediate vicinity did not prevent access of presumably Pol II to the CAT gene cassette. We propose that either CAT mRNA is synthesized by Pol II run-through transcription or by Pol II initiationupstream from the CAT gene.

Animals↗

Chromosome diversity of the genus Aotus from Colombia.

Description of six Colombian karyomorphs is completed through an extensive cytogenetic characterization of 35 Aotus (owl monkeys) specimens. The description of a new karyomorph for Colombian Aotus by chromosome on Q, G, R, and C, sequential banding is included. Pairs of karyomorphs 2 and 3 and 6 and 9 with 2n of 54, and 50, respectively, as well as karyomorphs 7 and 8 with 46 and 58 chromosomes were strongly suspected to represent different species on the grounds of large karyotypic differences. A proposal for a chromosome nomenclature of Aotus karyomorphs that aims to clarify Aotus taxonomy is presented which achieves a precise correspondence of different banding patterns, based on Q, G, R, and C sequential banding and chromosome measurements. Although our contribution is not a universal nomenclature system, unique criteria for chromosome denomination within Aotus karyomorphs are established. Previous systems of chromosome nomenclature have not successfully addressed the nomenclature of chromosomes of the same karyotype.

Animals↗

Effects of vasoactive drugs on gastric intramucosal pH.

OBJECTIVE: To review current knowledge about the effects of vasoactive agents on gastric intramucosal pH (pHi). DATA SOURCES: All studies involving pHi and vasoactive agents were retrieved from a computerized MEDLINE search from 1980 to 1997. We also reviewed the reference lists of all available review articles and primary studies to identify references not found in the computerized searches. STUDY SELECTION: Clinical and experimental studies using dopamine, dopexamine, dobutamine, norepinephrine, epinephrine, nitric oxide, N-acetylcysteine, prostaglandins, or pentoxifylline were considered if splanchnic perfusion and/or pHi measurements were utilized. DATA EXTRACTION: From the selected studies, information was obtained regarding patient population, dosing regimen, duration of study, and effects on splanchnic blood flow (SBF), splanchnic oxygenation, and pHi. DATA SYNTHESIS: Although dopaminergic effects increase SBF, dopamine does not generally increase pHi. Data on the effects of dopexamine on pHi are scarce and inconsistent. Dobutamine can significantly increase SBF and usually increases pHi. In septic patients, norepinephrine seems to increase pHi. Epinephrine may have detrimental effects on gastric perfusion. Prostacyclin seems to increase pHi but data are limited. Insufficient evidence exists to support the beneficial effects of nitric oxide donors or blockers, pentoxifylline, or N-acetylcysteine on pHi. CONCLUSIONS: Overall, the effects of vasoactive agents on pHi are unpredictable. Among the catecholamines, dopamine is the least likely, and dobutamine the most likely, to increase pHi.

Acetylcysteine↗

Has the mortality of septic shock changed with time.

OBJECTIVES: To determine whether a systematic review of the literature could identify changes in the mortality of septic shock over time. DATA SOURCES: A review of all relevant papers from 1958 to August 1997, identified through a MEDLINE search and from the bibliographies of articles identified. DATA SYNTHESIS: The search identified 131 studies (99 prospective and 32 retrospective) involving a total of 10,694 patients. The patients' mean age was 57 yrs with no change over time. The overall mortality rate in the 131 studies was 49.7%. There was an overall significant trend of decreased mortality over the period studied (r=.49, p < .05). The mortality rate in those patients with bacteremia as an entry criterion was greater than that rate in patients whose entry criterion was sepsis without definite bacteremia (52.1% vs. 49.1%; chi2=6.1 and p< .05). The site of infection altered noticeably over the years. Chest-related infections increased over time, with Gram-negative infections becoming proportionately less common. If all other organisms and mixed infections are included with the Gram-positives, the result is more dramatic, with these organisms being causative in just 10% of infections between 1958 and 1979 but in 31% of infections between 1980 and 1997. CONCLUSIONS: The present review showed a slight reduction in mortality from septic shock over the years, although this result should be approached with caution. The heterogeneity of the articles and absence of a severity score for most of the studies limited our analysis. Furthermore, there was an increasing prevalence of Gram-positive causative organisms, and a change of the predominant origin of sepsis from the abdomen to the chest.

APACHE↗

Trypanosome capping enzymes display a novel two-domain structure.

The ubiquitous m7G cap of eukaryotic mRNAs and of precursors to the spliceosomal small nuclear RNAs (snRNAs) is the result of an essential RNA modification acquired during transcript elongation. In trypanosomes, the m7G cap is restricted to the spliced leader (SL) RNA and the precursors of U2, U3, and U4 snRNAs. mRNA capping in these organisms occurs posttranscriptionally by trans splicing, which transfers the capped SL sequence to the 5' ends of all mRNAs. The SL cap is the most elaborate cap structure known in nature and has been shown to consist of an m7G residue followed by four methylated nucleotides. Using Crithidia fasciculata, we have characterized and purified the guanylyltransferase (capping enzyme), which transfers GMP from GTP to the diphosphate end of RNA. The corresponding gene codes for a protein of 697 amino acids, with the carboxy-terminal half of the C. fasciculata guanylyltransferase containing the six signature motifs previously identified in yeast capping enzymes. The amino-terminal half contains a domain that displays no resemblance to any other domain associated with capping enzymes. Intriguingly, this region harbors a consensus sequence for a phosphate-binding loop which is found in ATP- and GTP-binding proteins. This two-domain structure is also present in the Trypanosoma brucei capping enzyme, which shows 44% overall identity with the C. fasciculata capping enzyme. Thus, this structure appears to be common to all trypanosomatid protozoa and defines a novel class of capping enzymes.

Amino Acid Sequence↗

Prevalence of hepatitis C virus antibodies in primary glomerulonephritis in Brazil.

The association between hepatitis B virus and membranous glomerulonephritis and membranoproliferative glomerulonephritis (MPGN) was first described in 1971. Recently, a similar association between hepatitis C virus (HCV) and glomerulonephritis (GN) has been reported. We investigated the prevalence of hepatitis C serum antibodies (anti-HCV) in patients with primary GN followed up at our Nephrology Outpatient Clinic between March 1993 and November 1995. The diagnosis of primary GN was established after excluding the presence of connective tissue disease, diabetes, infectious disease, and malignancy. Anti-HCV antibodies were detected by a second-generation enzyme immunosorbent assay and HCV RNA by polymerase chain reaction. Of 81 patients with primary GN, 24 had membranous glomerulonephritis, 17 MPGN, 15 minimal-change disease, 12 focal-segmental glomerulosclerosis, 9 diffuse proliferative GN, and 4 IgA nephropathy. Anti-HCV were detected in 2 cases (2.5%), both were HCV RNA positive and had a polyclonal mixed cryoglobulinemia (IgM-IgG). These 2 cases both came from the group of 17 patients with MPGN. Biochemical investigation in these patients revealed persistent elevation of serum aminotransferase activity, and a liver biopsy specimen in 1 of them showed evidence of chronic active hepatitis. We conclude that in our setting the prevalence of anti-HCV among patients with primary GN is low, being higher (11.8%) only if we consider the patients with MPGN as the reference group. Further studies are necessary to clarify this association and to determine appropriate therapy for these patients.

Adolescent↗

A randomized clinical trial of cryotherapy, laser vaporization, and loop electrosurgical excision for treatment of squamous intraepithelial lesions of the cervix.

OBJECTIVE: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). METHODS: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using chi2 statistics, logistic regression analysis, and the Cox proportional hazards model. RESULTS: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6-37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). CONCLUSION: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.

Adolescent↗

Unusual features of serous neoplasms of low malignant potential during pregnancy.

Ten serous neoplasms of low malignant potential (LMP) resected during pregnancy were found in the files of the University of Texas M. D. Anderson Cancer Center (UTMDACC). Microscopically, all tumors had marked epithelial proliferation with abundant eosinophilic cells, and eight had intraluminal mucin. Multiple areas of microinvasion were found in eight cases. Additional unusual features were found in three cases. One patient presented with a serous LMP tumor in a supraclavicular lymph node. After resection of an ovarian serous LMP tumor, she was treated with chemotherapy and is without evidence of disease after 21 years. One patient had tumor resected at 24 weeks of gestation and at 2 months postpartum. Marked regression of the epithelial proliferation, the number of eosinophilic cells, and the amount of mucin was seen in the second specimen. Another patient had multiple peritoneal nodules at cesarean section, one of which was biopsied and diagnosed as a primary serous LMP of the peritoneum with multiple areas of microinvasion. Two months later a diagnostic laparoscopy was performed and no residual disease was found. All patients are alive with no evidence of disease. In summary, serous LMP tumors during pregnancy have microscopic and clinical features suggesting aggressive behavior; however, these features appear to regress at the termination of the pregnancy.

Adult↗

Contributions of glutamate receptors to the maintenance of mustard oil-induced hyperalgesia in spinalized rats.

N-methyl-d-aspartate (NMDA) receptors, which are widely distributed throughout the central nervous system, appear to play a critical role in several types of plasticity and long-term potentiation. In the pain system, increased sensitivity to somatosensory stimuli, known as hyperalgesia and allodynia, can arise from tissue damage or excessive C-fiber nociceptor activation. Previously, NMDA, non-NMDA ionotropic, and metabotropic glutamate receptors have been proposed to contribute to the sustained hyperalgesia following tissue injury or nociceptor activation. Although non-NMDA receptors appear to mediate both hyperalgesia and normal (nonhyperalgesic) responses and behavior, NMDA receptors have been reported to participate only in hyperalgesic responses. In contrast, other studies have implicated NMDA receptors in both hyperalgesic and normal responses. The aim of this study was to critically compare the effects of the glutamate receptor antagonists ketamine and 2-amino-5-phosphonovaleric acid (APV; NMDA receptor antagonists), 6,7-dinitroquinoxaline-2,3-dione (DNQX; non-NMDA ionotropic receptor antagonist), and 2-amino-3-phosphonopropionic acid (AP3; metabotropic receptor antagonist) on intra-articular mustard oil-induced facilitation of flexion withdrawal reflexes in spinalized rats. Our results showed that, as expected from previous studies, ketamine, APV, and DNQX dose-dependently inhibited the flexion withdrawal reflex evoked by C-fiber electrical stimulation of the sciatic nerve. Surprisingly, however, ketamine, APV, and DNQX also inhibited flexion withdrawal reflexes in normal (nonhyperalgesic) rats with similar ED50s. In contrast, AP3 had no effect in either hyperalgesic or normal rats. These results demonstrate that NMDA and non-NMDA ionotropic, but not metabotropic, glutamate receptors contribute without preference to both facilitated and normal flexion withdrawal reflexes evoked by high-intensity electrical stimulation in the spinalized rat. Thus, the apparent preference of NMDA receptors for hyperalgesic states seen in some previous studies on nociception, as well as in other model systems, may have arisen from differences in experimental paradigm, such as the intensity of sensory stimulation or excitability of the spinal cord, coupled with the voltage dependency of the NMDA conductance.

Animals↗

Symmetrical enchondromatosis of the hands and feet in two sisters.

We report two Portuguese sisters aged 9 and 12 years with symmetric well-circumscribed radiolucent cystic lesions on the long bone metaphysis of the hands and feet. The eldest also has soft tissue calcifications. They have no dysmorphic features and their growth is normal. Plasma values of parathyroid hormone (PTH), calcium, phosphorus, magnesium, and alkaline phosphatase are normal. Cerebral computed tomography (CT) scan shows no intracranial calcifications. A Raynaud phenomenon became evident during the last year in the eldest. The incisional biopsy of the left proximal metatarsial was performed through an area of typical radiographic appearance. The pathology specimen consisted of enchondroma tissue. The present cases are an extremely rare instance of this pathology, with symmetrical involvement of the hands and feet and a familial incidence.

Adolescent↗

Contact allergy to gold sodium thiosulfate. A comparative study.

During 1995, we added gold sodium thiosulfate and potassium dicyanoaurate to the patch test standard series. Our purpose was to compare the reactivity of the gold salts, to determine the frequency of contact allergy to gold in our country, to compare our results with those of the Malmö group and, finally to try to clarify the clinical relevance 2853 patients were routinely tested and 168 patients answered a questionnaire similar to that used by the Malmö group. Contact allergy to gold was found in 23 patients, all women: 22 to gold sodium thiosulfate (0.78%), only 1 to potassium dicyanoaurate and 2 to both salts. All reactors had their ears pierced and were exposed to gold jewelery (mainly earrings). Simultaneous allergies to nickel and cobalt were statistically significant in patients with positive patch tests to gold sodium thiosulfate. Atopy was no more common among these patients.

Chi-Square Distribution↗

Noxious colorectal distention induced-c-Fos protein in limbic brain structures in the rat.

Colorectal distention is a non-invasive stimulus used to study visceral pain processing in the nervous system. In this study, immunocytochemical labeling for the immediate-early gene, c-Fos, was used to map limbic brain structures involved in processing visceral pain. Rats received noxious colorectal distention while loosely restrained or loose restraint without distention (control). The brains were immunostained and the density of Fos-labeled nuclei within areas of the brain associated with limbic function were examined. Many cortical (cingulate; retrosplenial; insular; perirhinal, entorhinal) and subcortical (periaqueductal gray; locus coeruleus; lateral parabrachial area; paraventricular, anterodorsal and centromedian thalamic nuclei; lateral septal area; dorsomedial hypothalamus; cortical amygdala; subiculum) areas were labeled in the control rats, but significantly more Fos was observed in these areas following noxious colorectal distention (CRD). Additional areas were labeled following CRD but not restraint (e.g. infralimbic and prelimbic cortices; mediodorsal thalamic nucleus; central amygdaloid nucleus). The results show that noxious visceral stimuli result in Fos expression in limbic structures that exceeds that induced by restraint stress, suggesting that different pathways and circuits are recruited by stimuli which can produce similar emotional responses.

Animals↗

Development of monoclonal antibodies against a riboflavin-tryptophan photoinduced adduct: reactivity to eye lens proteins.

We describe here the development of monoclonal antibodies to the hapten tryptophan-riboflavin, generated by irradiation of a solution of bovine serum albumin in the presence of riboflavin. The specificity of the three obtained monoclonal antibodies, named 1E6, 5H5, 5A8 all belonging to the IgG1 isotype, was assessed by a competitive enzyme-linked immunosorbent assay in the presence of an increasing concentration of the tryptophan-riboflavin adduct, obtained from an irradiated riboflavin-sensitized tryptophan solution. It was demonstrated that the tryptophan-riboflavin antibodies react with the soluble proteins of the eye lens; this reaction was more intense in the old rat lenses as compared to the young ones, and a maximum binding of the antibodies was obtained with the soluble protein fraction from the human cataractous lens. By indirect immunofluorescence, a reactivity associated with the protein matrix, localized in the lens central zone, was observed. In the peripheral zone of the lens, where the younger cells are found, a marked immunofluorescent emission was observed on structures preferentially localized in the nuclei.

Animals↗