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Biomedical subjects

C Brito

Publications and source records attributed to C Brito.

13 recordsLinked to original sources

Different expression levels of alpha3/4 fucosyltransferases and Lewis determinants in ovarian carcinoma tissues and cell lines.

Ovarian carcinoma is the leading cause of death from gynecological cancers in many countries. Fucosylated glycoconjugates have been associated with various carcinomas. In the present study, we have characterized the expression of alpha3/4 fucosyltransferases transcripts and their products, the Lewis carbohydrate determinants, and their in vitro specificity towards synthetic acceptors using ovarian carcinoma cell lines OVM, m130, GG and SKOV3. We found different expression patterns: GG cells expressed mostly Lewisx (Lex), Lewisy (Ley), sLea and Leb, and m130 cells expressed mostly Lex and Ley. The detection was on the plasma membrane and in intracellular vesicles. OVM and SKOV3 cells had very low amounts of staining. From RT-PCR studies, enzyme specificity of cellular extracts towards a panel of synthetic carbohydrate acceptors and Western blot analysis we concluded that Lea, sLea and Leb were synthesised by FUT3, whereas Lex and Ley were synthesized by FUT4 and FUT9 in both cell lines. The GG and m130 cell lines are adequate models to investigate the role of Lex, Ley, sLea and Leb in ovarian carcinoma development.

Adenocarcinoma, Mucinous↗

Cost effectiveness and delivery study for future HIV vaccines.

Research teams from five countries, Brazil, China, Kenya, Peru and Thailand, have initiated a policy-maker survey on vaccine delivery, cost studies for future HIV vaccination programmes, and associated simulation modeling exercises analysing the relative cost-effectiveness of potential HIV vaccination strategies. The survey assesses challenges and opportunities for future country-level HIV vaccination strategies, providing data on the vaccine characteristics (e.g. vaccine efficacies for susceptibility, infectiousness and disease progression) and vaccination programme strategies to be considered in the cost-effectiveness modeling analyses. The study will provide decision-makers with modeling data on vaccination policy considerations that will assist in developing country-level capacities for future HIV vaccine policy adoption and effective delivery systems, and will help delineate the long-term financial requirements for sustainable HIV vaccination programmes. The WHO-UNAIDS HIV Vaccine Initiative and the collaborating researchers welcome comments or questions from policy makers, health professionals and other stakeholders in the public and private sectors about this effort to help advance policy and capacity related to future potential HIV vaccines.

AIDS Vaccines↗

Deletion of the cytoplasmic domain of human alpha3/4 fucosyltransferase III causes the shift of the enzyme to early Golgi compartments.

The transmembrane domain (TM) and flanking regions of glycosyltransferases (GTs) have been implicated in the localization of these proteins in the Golgi apparatus (GA). alpha3/4 Fucosyltransferase III (FT3wt) (EC 2.4.1.65) is localized in the trans-Golgi and trans-Golgi network (TGN) of baby hamster kidney (BHK) cells and synthesizes Lewis determinants associated with cell adhesion events. We have evaluated the effect of removing the cytosolic domain on the localization of the enzyme and its capacity for synthesizing the Lewis A (Le A) determinant. The mutant where the cytoplasmic domain (Asp-2 to Trp-13) of FT3wt has been deleted (FT3dc) was localized in the Golgi but it was shifted to earlier compartments than FT3wt. The mutant was not detected on the plasma membrane (PM) and glycosylation analysis indicated that FT3dc was transported beyond the endoplasmic reticulum (ER) since complex type glycosylation was observed. Cells expressing FT3dc showed a significantly lower efficiency to synthesize Le A when compared with cells expressing FT3wt, in vivo. This reduction was not due to lower specific activity because both enzyme forms had a similar specific activity in vitro. Therefore, removal of FT3 cytosolic tail caused a shift in enzyme distribution to earlier Golgi compartments concomitant to the decrease of its biosynthetic capacity.

Animals↗

Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.

Functional inducible NOS (iNOS) may be involved in the prolonged lifespan of chronic lymphocytic leukemia cells (B-CLL), although the exact mechanisms implicated remain elusive as yet. In this work, we have examined iNOS expression in normal B lymphocytes and B-CLL cells in pro- and antiapoptotic conditions. Our results demonstrate: (1) The existence of a new splice variant characterized by a complete deletion of exon 14 (iNOS 13-16(14del)), which was preferentially detected in normal B lymphocytes and may represent an isoform that could play a role in the regulation of enzyme activity. (2) The existence of another alternatively spliced iNOS mRNA transcript involving a partial deletion of the flavodoxin region (iNOS 13-16(neg)) was correlated to a decreased B-CLL cell viability. The 9-beta-D-arabinofuranosyl-2-fluoradenine or fludarabine (F-ara) treatment induced iNOS 13-16(neg) transcript variants, whereas IL-4 enhanced both the transcription of variants, including these exons (iNOS 13-16(pos)), and the expression of a 122 kDa iNOS protein. These results suggest that in B-CLL, a regulation process involving nitric oxide (.- NO) levels could occur by a post-transcriptional mechanism mediated by soluble factors. Our results also provide an insight into a new complementary proapoptotic action of F-ara in B-CLL by the induction of particular iNOS splice variants, leading to the activation of a caspase-3-dependent apoptotic pathway.

Aged↗

Peroxynitrite inhibits T lymphocyte activation and proliferation by promoting impairment of tyrosine phosphorylation and peroxynitrite-driven apoptotic death.

Peroxynitrite (ONOO-) is a potent oxidizing and nitrating agent produced by the reaction of nitric oxide with superoxide. It readily nitrates phenolic compounds such as tyrosine residues in proteins, and it has been demonstrated that nitration of tyrosine residues in proteins inhibits their phosphorylation. During immune responses, tyrosine phosphorylation of key substrates by protein tyrosine kinases is the earliest of the intracellular signaling pathways following activation through the TCR complex. This work was aimed to evaluate the effects of ONOO- on lymphocyte tyrosine phosphorylation, proliferation, and survival. Additionally, we studied the generation of nitrating species in vivo and in vitro during immune activation. Our results demonstrate that ONOO-, through nitration of tyrosine residues, is able to inhibit activation-induced protein tyrosine phosphorylation in purified lymphocytes and prime them to undergo apoptotic cell death after PHA- or CD3-mediated activation but not upon phorbol ester-mediated stimulation. We also provide evidence indicating that peroxynitrite is produced during in vitro immune activation, mainly by cells of the monocyte/macrophage lineage. Furthermore, immunohistochemical studies demonstrate the in vivo generation of nitrating species in human lymph nodes undergoing mild to strong immune activation. Our results point to a physiological role for ONOO- as a down-modulator of immune responses and also as key mediator in cellular and tissue injury associated with chronic activation of the immune system.

Apoptosis↗

Long- and short-term variability of automated perimetry results in patients with optic neuritis and healthy subjects.

OBJECTIVE: To measure the short- and long-term variability of automated perimetry in patients with optic neuritis and normal subjects. DESIGN: Prospective case-control design of patients with recovered optic neuritis with intraday and interday repetitions to obtain robust variability measurements. Entry criteria included a corrected pattern SD that was worse than the normal 5% probability level and a mean deviation worse than -3 dB but better than -20 dB. Five Humphrey 30-2 full threshold tests were administered during a 7-hour period (1 test every 2 hours) on the same day and at the same periods on 5 separate days. SUBJECTS: Seventeen patients with recovered optic neuritis and 10 healthy subjects of similar age. MAIN OUTCOME MEASURES: Short-term variability and long-term variability for global visual field data. RESULTS: Patients with optic neuritis demonstrated variations in visual field sensitivity that were outside the entire range of variability for normal controls. These variations occurred for multiple tests performed on the same day at specific times and for tests performed at specific times on different days. There were no consistent patterns of sensitivity changes that could be attributed to time of day. The most dramatic fluctuations occurred in a patient whose visual fields varied from normal to a hemianopic defect from one week to another and from a partial quadrant loss to a hemianopic defect at different times on the same day. Seven of the patients with optic neuritis also demonstrated intermittent vertical step defects. CONCLUSIONS: Patients with resolved optic neuritis can have large variations in visual field results on different days and at different times on the same day. The variations affect both the severity and the pattern of visual field loss and do not appear to be consistent across patients. These data indicate that care must be taken when automated visual field results in patients with optic neuritis are interpreted. Distinguishing systematic changes in sensitivity from variability requires more than a comparison of the current visual field with the most recent previous visual field.

Adult↗

Genital infections among antenatal care attendees in Cape Verde.

In a cross-sectional study, 350 pregnant Capeverdian women were examined to assess the prevalence of Chlamydia trachomatis infection (CT), Neisseria gonorrhoeae infection (NG) and Bacterial vaginosis (BV). Among various analytic methods used, the polymerase chain reaction PCR (for NG, CT) yielded a higher detection rate than did direct microscopy or culture (NG), or direct immuno-fluorescence (CT). Since the PCR analytic of air-dried specimens is not hampered by harsh storage and transport conditions, it could serve to validate other detection methods where laboratory facilities are suboptimal. Among sociodemographic risk factors young age, and currently living alone, were significantly associated with infection.

Adult↗

An ultraviolet light sensitive target in nitrate reductase of Escherichia coli K-12.

Ultraviolet light was shown to inactivate purified nitrate reductase in the presence of reduced benzyl viologen. Loss of activity was not complete, reaching 60 to 70%. Photolysis was maximum at 345 nm. The differential spectrum between native and irradiated enzyme exhibited absorption bands at 216, 275, 314 and 365 nm. The photosensitive electron carrier could be extracted by organic solvents. It had the following absorption bands: 225, 275 and 285 nm. It was reduced by Nile blue A but not by methylene blue. The precise nature of this light sensitive molecule could not be determined although the results support the idea that this chromophore might be a naphthoquinone.

Escherichia coli↗

[Terrien's disease].

A clinical review of the Terrien's corneal disease, based on the observation of five atypical clinical cases, was conducted in relation to the age which the clinical picture appeared, or to its association with other ocular pathology such as keratoconus, cataract, and conjunctivolimbic epidermoid carcinoma. The technique for surgical treatment of advanced peripheral corneal ectasis employing a semilunar lamellar keratoplasty is described. This was performed on one patient, with good results.

Adult↗

Histological evidence for adulticidal effect of low doses of diethylcarbamazine in bancroftian filariasis.

The ability of diethylcarbamazine (DEC) to kill adult Wuchereria bancrofti worms was evaluated by examining lymphatic nodules formed after treatment with 4 different treatment schedules of 193 males living in the endemic area of Greater Recife, Brazil. Lymphatic nodules appeared in the spermatic cord or upper extremities in 43 of 138 microfilaraemic individuals, in 3 of 30 amicrofilaraemic patients with filarial disease manifestations, and in 1 of 25 asymptomatic amicrofilaraemic residents of the endemic area treated with DEC. Fourteen of these nodules were surgically removed 10-150 d after the start of treatment. Regardless of the DEC dosage and schedule used, all nodules contained damaged and degenerating adult worms. An exuberant granulomatous process with large numbers of eosinophils and progressive fibrosis gradually developed around the dead parasites. The mechanism(s) by which DEC killed adult W. bancrofti could not be determined.

Adolescent↗

Granular dystrophy associated with congenital cataracts.

Seven members of the same family suffering from Groenow I granular dystrophy and associated congenital cataracts have been studied. Three patients had corneal dystrophy at various stages and three others had a fetal nuclear congenital cataract. A penetrating keratoplasty button was studied under light and electron microscopies. This association has not been described previously. However we must emphasize that there is no general validity for a correlation between granular dystrophy and congenital cataract.

Adolescent↗