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Biomedical subjects

C B Pereira

Publications and source records attributed to C B Pereira.

At least 19 recordsLinked to original sources

Different kinetics in anti-cytomegalovirus immunity reconstitution evaluated by lymphocyte proliferation and IFN-gamma production in allogeneic and autologous bone marrow transplantation.

Allogeneic bone marrow transplantation (ALLOBMT) is associated with an increased risk of cytomegalovirus (CMV) morbidity compared to autologous BMT (AUTOBMT). To investigate this, we evaluated AUTOBMT and ALLOBMT patients regarding anti-CMV immune reconstitution at 1 and 4 months after BMT and on the day after first CMV antigenemia detection. Intermittent ganciclovir preemptive therapy was prompted by antigenemia of >or=2 cells. One month after transplant, AUTOBMT recipients already displayed larger CD8+ T cell numbers than ALLOBMT recipients, but comparably small CD4+ T cell numbers. Most AUTOBMT patients had positive CMV antigen (CMV-Ag)-induced lymphoproliferation (86%) and IFN-gamma secretion (86%), whereas this was infrequently seen in ALLOBMT patients (20 and 10%, respectively). This early AUTOBMT immune reconstitution was associated with a lower frequency of CMV reactivation up to +4 months in AUTOBMT (21%) than ALLOBMT patients (91%). At +4 months, most ALLOBMT recipients had also recovered CMV-Ag immune responses. At first antigenemia detection, all 3 AUTOBMT recipients already displayed anti-CMV immune functions and 2 cleared the infection without therapy, whereas of the 10 ALLOBMT recipients only 1 had positive lymphoproliferation. In the latter group, none had IFN-gamma secretion or cleared the infection without therapy. Thus, differences in anti-CMV immune reconstitution may help to explain the contrasting rates of CMV morbidity between ALLOBMT and AUTOBMT patients.

Adolescent↗

Application of matrix solid-phase dispersion in the determination of dibenzo[a,l]pyrene content of experimental animal diets used in a large-scale tumor study.

A method utilizing matrix solid-phase dispersion (MSPD) was developed for isolation and determination of dibenzo[a,l]pyrene (DBP) in experimental rainbow-trout diets used in a large-scale carcinogenesis study. A 0.5 g sample of moist ration containing 0-225 ppm DBP (dry basis) was mixed with 2 g C18 sorbent and benzo[a]pyrene internal standard was added to the mixture. Extraction and clean-up were accomplished in a single step by extracting the sample mixture with hexane-benzene 4:1 from a cartridge containing 2 g Florisil. DBP was quantified by HPLC on a C5 bonded phase column with fluorescence detection. Mean analytical recovery of DBP from control diet spiked at three concentration levels was 101 to 107% with relative standard deviations of 1 to 7%. The limit of detection of DBP was equivalent to 0.014 ppm in the ration. Application of the method to verification of DBP levels in trout rations from the carcinogenesis study is described. Control ration (0 ppm DBP) was screened for possible DBP contamination and none was found. This is the first report on analysis of DBP in experimental animal diets.

Animal Feed↗

Smoking and balance: correlation of nicotine-induced nystagmus and postural body sway.

Unaccustomed smoking may elicit transient nystagmus, dizziness, unsteadiness, and nausea. Infrared videonystagmography and posturography were performed simultaneously to study the differential effects of nicotine on the association of ocular motor and postural disturbances in 25 non- or occasional smokers. Sixteen showed nicotine-induced nystagmus (NIN) of various directions (mainly horizontal or upbeat) which was associated with a significant increase in postural sway after smoking a cigarette (total sway path (SP) before smoking 2.22 +/- 0.82 m/min (mean +/- s.d.), 1 min after smoking 3.83 +/- 1.41 m/min; p < 0.0004, ANOVA); nine showed neither effect. There was a high correlation between the intensity of the nystagmus (measured as peak slow phase velocity) and the increase in total SP (correlation coefficient 0.78) as well as the time courses of both. Visual fixation of an LED integrated in the mask not only caused a suppression of NIN but also a decrease in body sway. Transient ocular motor and postural effects are compatible with simultaneous nicotine-induced effects on the vestibulo-ocular and vestibulo-spinal functions.

Adult↗

Characterization of expressed full-length and truncated FMO2 from rhesus monkey.

Flavin-containing monooxygenase (FMO) metabolizes a wide variety of nitrogen, sulfur, and phosphorous-containing xenobiotics. FMO2 is highly expressed in the lung of most mammals examined, but the protein has only recently been detected in humans, presumably due to a premature stop codon at AA472 in most individuals. In this study, full-length (mFMO2-535) and 3'-truncated (mFMO2-471) monkey FMO2 protein, produced by cDNA-mediated baculovirus expression, were characterized and compared with baculovirus-expressed rabbit FMO2 (rFMO2-535). Although baculovirus-expressed mFMO2-535 had properties similar to FMO in monkey lung microsomes and had catalytic properties similar to rFMO2-535, the expressed proteins differed in a number of properties in S-oxidation assays. Both enzymes had the same pH optima (pH 9.5); however, mFMO2-535 quickly lost activity at higher pH values whereas rFMO2-535 retained the majority of its activity. Also, mFMO2-535 was significantly less stable at elevated temperatures and in the presence of cholic acid but had greater activity in the presence of magnesium. mFMO2-535 had higher apparent K(m) and V(max)/K(m) values than rFMO2-535 did in N-oxygenation assays. mFMO2-471 was correctly targeted to the membrane fraction, but N- and S-oxygenation was not detected. Since the AA sequence identity of mFMO2 and human FMO2 is 97%, our results with mFMO2-535 suggest that individuals carrying the allele encoding full-length FMO2 are likely to have in vivo FMO2 activity. Such activity could result in marked differences in the metabolism, efficacy, and/or toxicity of drugs and xenobiotics for which lung is a portal of entry or target organ.

Animals↗

[Benign paroxysmal positioning vertigo].

Benign paroxysmal positioning vertigo is a frequent vestibular disorder. With a simple maneuver one can easily diagnose this condition and treatment is based on liberatory maneuvers. On this review the pathogenesis, the clinical features and different maneuvers are briefly discussed.

Humans↗

Nicotine-induced nystagmus: three-dimensional analysis and dependence on head position.

Two- and three-dimensional analyses of nicotine-induced eye movements were performed in 53 subjects to evaluate whether they were primarily of vestibular or ocular motor origin. Nicotine-induced nystagmus was detected in 27 subjects (51%); in 25 of these (93%) it was modulated by otolith input. Three-dimensional analysis of nicotine-induced nystagmus revealed that it violates Listing's law. Taken together, these findings suggest that nicotine induces an imbalance in the vestibulo-ocular reflex.

Adult↗

Potency of dietary indole-3-carbinol as a promoter of aflatoxin B1-initiated hepatocarcinogenesis: results from a 9000 animal tumor study.

Indole-3-carbinol (I3C), a metabolite of glucobrassicin found in cruciferous vegetables, is documented as acting as a modulator of carcinogenesis and, depending on timing and dose of administration, it may promote hepatocarcinogenesis in some animal models. In this study we demonstrate that, when given post-initiation, dietary I3C promotes aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rainbow trout model at levels as low as 500 p.p.m. Trout embryos (approximately 9000) were initiated with 0, 25, 50, 100, 175 or 250 p.p.b. AFB1 by a 30 min immersion. Experimental diets containing 0, 250, 500, 750, 1000 or 1250 p.p.m. I3C were administered starting at 3 months and fish were sampled for liver tumors at 11-13 months. Promotion at the level of tumor incidence was statistically significant for all dietary levels, except 250 p.p.m. Relative potency for promotion markedly increased at dietary levels >750 p.p.m. We propose that more than one mechanism could be involved in promotion and that both estrogenic and Ah receptor-mediated pathways could be active. The estrogenicity of I3C, measured as its ability to induce vitellogenin (an estrogen biomarker in oviparous vertebrates) was evident at the lowest dietary level (250 p.p.m.), whereas CYPIA (a P450 isozyme induced through the Ah receptor pathway) was not induced until dietary levels of 1000 p.p.m. Therefore, at lower dietary levels, promotion by I3C in this model could be explained by estrogenic activities of I3C acid derivatives, as it is known that estrogens promote hepatocarcinogenesis in trout. Much stronger promotion was observed at high dietary I3C levels (1000 and 1250 p.p.m.), at which levels both CYP1A and vitellogenin were induced.

Aflatoxin B1↗

Effects of stress on the reproductive performance of rainbow trout (Oncorhynchus mykiss).

We investigated the effects of stress over the final stages of sexual maturation on the reproductive performance of female rainbow trout, Oncorhynchus mykiss. Stress was administered over the period of early vitellogenesis (1.5 mo), late vitellogenesis-final maturation (1.5 mo), or during both periods (3 mo). Each stress treatment and control was triplicated, with eight females in each replicate (n = 24 fish per treatment). The eggs and progeny of each female were kept separate, and observations were made for 4 mo after transfer to rearing tanks. Fish that experienced stress during final maturation and those that were under stress during the whole experiment ovulated on average 2 wk earlier than the control group. In contrast, fish stressed during the period of early vitellogenesis ovulated at the same time as controls. Absolute fecundity and fertilization were not significantly affected in any treatment group, but significant differences in relative fecundity were found. Stress applied early in vitellogenesis resulted in smaller eggs and swim-up fry. No significant differences were found in juvenile weight 8 wk after hatching. Furthermore, we found no differences in survival of the progeny or resistance to the fish pathogen Vibrio anguillarum. Thus, mild acute stresses applied to rainbow trout females may affect certain reproductive performance parameters such as timing of ovulation and relative fecundity; however, the progeny of such stressed females perform as well as controls with regard to juvenile growth and disease resistance.

Animals↗

Phenotypic analysis of spleen, thymus, and peripheral blood cells in aged C57B1/6 mice following long-term exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

A mouse model was used to identify potential biomarkers of exposure to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Female C57B1/6 mice were treated weekly with 0.2 microgram TCDD/kg body weight or vehicle for 14-15 months. Phenotypic analysis by flow cytometry identified the major cell subpopulations in the spleen, thymus, and peripheral blood as defined by the expression of CD4, CD8, B220, and Mac-1 molecules. These subpopulations were further characterized for the expression of I-A, Pgp-1, CD45RB, and/or T cell receptor antigens (CD3, alpha beta, gamma delta). A group of young (4 months old) mice was evaluated concurrently to document immunophenotype alterations associated with aging. Results showed several age-related changes in phenotype distribution in the spleen and blood, but not in the thymus, despite significant age-dependent thymic involution. The age-dependent changes in splenic phenotypes included a decreased frequency of CD4+ cells and a major shift in the frequency distribution from naive T cells to effector and memory T cells as defined by Pgp-1 and CD45RB expression. These phenotypic changes in the spleen due to aging correlated with similar changes in the blood, providing preliminary support for the use of spleen cells as surrogates for blood in the development of biomarkers of immunotoxicity. In comparison to the effects of aging, TCDD treatment produced relatively subtle changes in immunophenotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Long-term, high-dose dietary exposure of rainbow trout to butylated hydroxyanisole is non-carcinogenic.

The hepatocarcinogenic and/or promotional properties of butylated hydroxyanisole (BHA) were tested in rainbow trout. Four groups of 100, 21-day-old trout embryos were exposed to 0.5 ppm aqueous aflatoxin B1 (AFB1) for 30 min, and four similar groups were sham treated. After hatching, swim-up, and the onset of vigorous feeding behavior (2 weeks pest swim-up), duplicate groups of 60 AFB1-treated and sham-treated fry were started on a test diet containing 0.6% (6000 ppm) BHA, and the other duplicate groups of treated and untreated fry were fed the control Oregon Test Diet (OTD). After 8 months of feeding BHA or OTD, the fish were necropsied for tumor detection, with particular attention given to the stomach and liver. No tumors were seen in the livers or stomachs of the sham-treated fish fed OTD or BHA, showing that BHA is not carcinogenic to rainbow trout under the conditions of this experiment. Promotional results were equivocal, with one tank of fish having a higher hepatic tumor incidence, but the other the same as the positive AFB1 control. When the tanks were combined, however, there was no statistical difference between the two groups.

Animals↗

Dose-dependent carcinogenicity and frequent Ki-ras proto-oncogene activation by dietary N-nitrosodiethylamine in rainbow trout.

While the experimental data upon which current concepts in mechanistically based risk assessment and molecular epidemiology are grounded derive almost entirely from rodent models, fish models have several attributes (e.g., low background incidence, extremely low cost tumor studies, nonmammalian comparative status for extrapolation of mechanisms to humans) that make them valuable adjuncts for addressing these concepts. This report provides an initial characterization of the dose dependency of dietary N-nitrosodiethylamine (DEN) hepatocarcinogenicity in Shasta strain rainbow trout (Oncorhynchus mykiss) and the potential of DEN to elicit ras proto-oncogene activation in this species. Carcinogen was administered in the diet at five concentrations for 12 months. Necropsies were performed at 9, 12, and 18 months, the latter on fish maintained on control diet for 6 months after cessation of DEN exposure. The incidence of hepatic neoplasms at the lower dietary concentrations (< or = 70 ppm) did not consistently exceed that for control groups, which were higher in this particular study (2%) than expected (historically 0.1%). For the higher DEN concentrations, a linear relationship between the hepatic tumor incidence (expressed as log odds, log [p/(1-p)], where p = proportion of fish bearing tumors), and the logarithm of total cumulative dose was observed, with response being independent of the length of time (9 or 12 months) during which the dose was accumulated. The dose-response curve for fish maintained an additional 6 months postexposure was shifted toward higher incidence but was parallel to the curve for fish killed at cessation of exposure. The model predicts that doubling the dose will produce somewhat more than a doubling of the odds (p/(100-p)) for tumor incidence and that the odds for lesions 6 months postexposure will be approximately double those at cessation of exposure. Comparison of these results with previous studies using rats suggests an overall similarity in dose-response curves, with trout being somewhat less sensitive than rats to DEN hepatocarcinogenesis. To examine the molecular basis for DEN carcinogenesis in this species, seven liver tumors induced separately by short-term DEN treatment were probed by 3'-mismatch primer polymerase chain reaction analysis for evidence of Ki-ras proto-oncogene activating point mutations. A very high proportion (6/7) of tumors was found to carry codon 12 GGA-->AGA mutations, whereas no codon 61 mutants were detected in this sample.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

In vitro steroid secretion during early development of mono-sex rainbow trout: sex differences, onset of pituitary control, and effects of dietary steroid treatment.

Sex differentiation in many teleost species can be controlled by treatment with steroids. To investigate the development of steroidogenesis during both natural and controlled sex differentiation, the production of androstenedione, testosterone, and estradiol were determined in tissues from populations of all-female and all-male rainbow trout (Oncorhynchus mykiss). At various times from hatching through gonadal sex differentiation, explants of steroidogenic tissues were incubated in vitro alone or in the presence of partly purified salmon gonadotropin and the resulting media were assayed for steroids. Androstenedione and testosterone were produced at higher levels in media from testes than from ovaries within 2 weeks of the onset of feeding (before any dramatic gonadal differentiation). Gonadal estradiol secretion was nondetectable until about 1 month after the onset of feeding when females produced more than males. Gonadotropin stimulated gonadal steroid production only after differentiation, but stimulated anterior kidney (interrenal) production of androstenedione much earlier in development. Dietary treatment of rainbow trout with either estradiol or 17 alpha-methyltestosterone (MT) inhibited in vitro gonadal steroid production and this effect persisted in MT-fed fish even after withdrawal of dietary steroids.

Aging↗

Effects of atenolol in patients with reciprocating supraventricular tachycardia.

We studied 12 patients with crisis of paroxysmal reciprocating supraventricular tachycardia before and after intravenous injection of 5 mg of atenolol. The patients were then followed for periods ranging from 6 to 50 months (median 34 months). During this time, they received oral atenolol therapy, at 200 mg for the first two weeks, and 100 mg daily thereafter. Tachycardia was due to reciprocation within the atrioventricular node in 9 patients, and to pre-excitation in 3 patients. Atenolol slowed the sinus rate, prolonged the atrioventricular conduction time, and increased the atrial cycle length at which atrioventricular nodal Wenckebach phenomenon occurred. During the tachycardia, atenolol increased the tachycardia During the tachycardia, atenolol increased the tachycardia cycle length, due to prolongation of the intranodal atrioventricular conduction time. Of the 11 patients who were observed for the full period, 7 had no further episodes of arrhythmia. One patient (with left-sided pre-excitation) failed to respond to any antiarrhythmic medication, one patient remained free of symptoms for two years, but received an atrial pacemaker for control of the tachycardia at the end of this period. Two patients (one with dual atrioventricular nodal pathways, and one with concealed left-sided pre-excitation) await other treatment for their tachycardia, after remaining free of symptoms for one and two years, respectively. These findings suggest that atenolol is an effective beta blocker for use in controlling arrhythmias in patients with reciprocating supraventricular tachycardia, for use in once daily dosage, and is a medication largely free of side effects.

Adult↗

Tachycardia mediated by an AV universal (DDD) pacemaker triggered by a ventricular depolarization.

A 44-year-old female had Chagas' disease with right bundle branch block, right axis deviation, and ventricular ectopic beats. An invasive evaluation showed a prolonged HV interval of 100 ms. A Medtronic Versatrax 7000 was implanted, after which a pacemaker-mediated tachycardia was observed. The esophageal lead ruled out the possibility of an atrial triggered tachycardia. The diagnosis was pacemaker-mediated tachycardia due to abnormal sensing of the terminal forces of the ventricular activation because of malposition of the atrial lead in the right ventricular out-flow tract.

Adult↗