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Biomedical subjects

E Suarez

Publications and source records attributed to E Suarez.

At least 19 recordsLinked to original sources

Production of antigen-specific human monoclonal antibodies: comparison of mice carrying IgH/kappa or IgH/kappa/lambda transloci.

Here we compare human monoclonal antibody (MAb) production from mouse strains that carry disruptions of their endogenous mouse IgH/IgK loci and harbor human IgM + Igkappa(BABkappa) or human IgM + Igkappa + IgA transloci (BABkappa,lambda). We found that whereas both strains proved effective for the isolation of antigen-specific IgM antibodies, many of the IgM MAbs elicited from BABkappa comprise human mu chains that are associated with mouse lambda chains. In contrast, BABkappa,lambda mice gave rise to fully functional, polymeric human IgM antibodies comprising both human IgH and human IgL chains. Therefore, the inclusion of a human Iglambda translocus (in addition to the human IgH + Igkappa transloci) not only diminishes problems of endogenous mouse Iglambda expression but also provides a strain of mice that yields fully human MAbs to a wide range of antigens, as witnessed by the isolation of MAbs to human blood cells, tumor cell lines, and an immunoglobulin idiotype.

Animals↗

Rhegmatogenous retinal detachment in myopic eyes after laser in situ keratomileusis. Frequency, characteristics, and mechanism.

PURPOSE: To report the characteristics and frequency of rhegmatogenous retinal detachment (RRD) after laser in situ keratomileusis (LASIK) for the correction of myopia in a large case series. SETTING: Private practices, Caracas, Venezuela. METHODS: Five refractive surgeons and 31 739 myopic eyes that had surgical correction of a mean myopia of -6.01 diopters (D) (range -0.75 to -29.00 D) participated in this study. Laser in situ keratomileusis was performed in all eyes. Patients were followed for a mean of 36 months (range 6 to 48 months). The clinical charts of patients who developed RRD after LASIK were reviewed. RESULTS: Twenty eyes (17 patients) developed RRD after LASIK. Rhegmatogenous retinal detachments occurred a mean of 13.9 months (range 1 to 36 months) after LASIK. The mean pre-LASIK myopia in eyes that developed an RRD was -7.02 D (range -1.50 to -16.00 D). Most RRDs and retinal breaks occurred in the temporal quadrants (71.4%). Rhegmatogenous retinal detachments were managed with vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or pneumatic retinopexy techniques. The frequency of RRD after LASIK was 0.06%. CONCLUSIONS: Rhegmatogenous retinal detachment after LASIK for the correction of myopia is infrequent. If managed promptly, RRD will result in good vision. Before LASIK is performed, patients should have a thorough dilated indirect fundoscopy with scleral depression and treatment of any retinal lesion predisposing to the development of an RRD.

Adolescent↗

Antitubercular activity of triterpenoids from Lippia turbinata.

Assay-guided fractionation of the antitubercular MeOH-CH(2)Cl(2) extract obtained from Lippia turbinata led to the isolation of four novel triterpenoids-3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-(3-methylbut-2-en-1-oyloxy)olean-12-ene-28-oic acid (1); 3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-angeloyloxyolean-12-ene-28-oic acid (2); 3beta,25-epoxy-3alpha,21alpha-dihydroxy-22beta-tigloyloxyolean-12-ene-28-oic acid (3); and 3beta,25-epoxy-3alpha-hydroxy-22beta-(2-methylbutan-1-oyloxy)olean-12-ene-28-oic acid (4)-together with the known triterpenoids lantanilic acid (5), camaric acid (6), lantanolic acid (7), and rehmannic acid (8). The MIC values of 1-8 for growth inhibition of Mycobacterium tuberculosis were determined in the radiorespirometric BACTEC system.

Animals↗

Altered disposition and effect of lerisetron in rats with elevated alpha 1-acid glycoprotein levels.

PURPOSE: To examine the effect of changes in plasma alpha1-acid glycoprotein (AAG) levels on the pharmacokinetics (PK) and pharmacodynamics (PD) of lerisetron, a novel serotonin 5-HT3 receptor antagonist, in the rat. METHODS: After subcutaneous administration of turpentine oil, AAG was significantly elevated compared with controls. The PK of unchanged lerisetron (UL; high-performance liquid chromatography with radioactivity monitoring) and total lerisetron (TL; unchanged + changed, scintillation counting) was characterized post intravenous (i.v.) 14C lerisetron (50 microg/kg) in control and turpentine oil pretreated rats. The PK (0-180 min) was described by a two-compartmental model. Protein binding of lerisetron in vitro was measured using an ultrafiltration technique. The effect of lerisetron (5 microg/kg, i.v.) over 180 min was measured in anesthetized rats (control and pretreated) with the Bezold-Jarisch reflex (inhibition of bradycardia after 16 microg/kg serotonin i.v.) as the endpoint. PD parameters were estimated by sigmoid Emax models. RESULTS: The unbound fraction was significantly diminished in pretreated rats (mean +/- SEM) (6.60 +/- 1.23% vs. control 14.4 +/- 1.40%, P < 0.05). Volume of distribution (V) and clearance for UL and TL were significantly decreased when compared to the controls (P < 0.0001 for UL and P < 0.05 for TL). Plasma clearance based on unbound concentration for UL did not differ between groups but the unbound V and steady-state unbound V remained decreased (P < 0.05 and P < 0.0001). Pretreated rats showed a significantly diminished drug effect: the area under the E-t curve over 180 min was (mean +/- SEM) 5,189 +/- 657.7 in control animals vs. 3,486 +/- 464.4 in the pretreated group (P < 0.05). The EC50 (concentration at half maximum effect) for UL and TL were increased in pretreated rats and were not compensated when the unbound concentration was used. CONCLUSIONS: An increase in AAG causes alterations in the PK and PD of lerisetron, and because this is not compensated with the unbound concentration, we suggest that mechanisms not linked to protein binding may be involved.

Animals↗

Tandem radical decarboxylation-oxidation of amino acids: A mild and efficient method for the generation of N-acyliminium ions and their nucleophilic trapping

A convenient methodology for the synthesis of 2-substituted pyrrolidines from alpha-amino acids is described. A number of cyclic and acyclic alpha-amino acid derivatives have been prepared in order to test the scope and diastereoselectivity of this method. These substrates were treated with iodosylbenzene or (diacetoxyiodo)benzene (DIB) and iodine in order to generate the corresponding carboxyl radical, which evolves by loss of carbon dioxide to produce a carbon radical which in turn undergoes oxidation to an N-acyliminium ion. This postulated intermediate could be trapped inter- or intramolecularly by oxygen, nitrogen and carbon nucleophiles. In the case of carbon nucleophiles, a Lewis acid is required for the concomitant carbon-carbon bond formation. High yields and modest diastereoselectivities were obtained. The present methodology was applied to the synthesis of omega-amino aldehydes or hemiaminals 8-14, 2-aminopyrrolidine derivative 15, aminolactone derivative 16, and azasugar analogues 17 and 18. When carbon nucleophiles were used, alkaloid precursors such as 2-allyl- or 2-alkylpyrrolidines 19-23 and 25 were obtained.

Journal Article↗

Incidence of vitreoretinal pathologic conditions within 24 months after laser in situ keratomileusis.

OBJECTIVE: To report for the first time a case series of vitreoretinal pathologic conditions after laser in situ keratomileusis (LASIK) and to determine its incidence. DESIGN: Case series. PARTICIPANTS: Five refractive surgeons and 29,916 eyes that underwent surgical correction of ametropia (83.2% were myopic) ranging from -0.75 to -29.00 diopters (D; mean: -6.19 D) and from +1.00 to +6.00 D (mean: +3.23 D) participated in this retrospective study. MAIN OUTCOME MEASURES: Vitreoretinal complications after LASIK. RESULTS: The clinical findings of 20 eyes (17 patients) with LASIK-related vitreoretinal pathologic conditions are presented. Fourteen eyes experienced rhegmatogenous retinal detachments (RDs). Two eyes experienced corneoscleral perforations with the surgical microkeratome when a corneal flap was being performed (one experienced a vitreous hemorrhage and the other later experienced an RD). In four eyes, retinal tears without RDs were found. In one eye, a juxtafoveal choroidal neovascular membrane (CNVM) developed. Retinal tears were treated with argon laser retinopexy or cryotherapy. Corneoscleral perforations were sutured, and the RD was managed with vitrectomy. The remaining RDs were managed with vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or pneumatic retinopexy techniques. The CNVM was surgically removed. The incidence of vitreoretinal pathologic conditions determined in our study was 0.06%. CONCLUSIONS: Serious complications after LASIK are infrequent. Vitreoretinal pathologic conditions, if managed promptly, will still result in good vision. It is very important to inform patients that LASIK only corrects the refractive aspect of myopia. Complications of the myopic eye will persist.

Adolescent↗

Leptin and IGF-I levels in unconditioned male volunteers after short-term exercise.

We have previously shown that serum gonadotropins, particularly LH, decline after acute exercise in male volunteers. The mechanism for this decline is unknown. Plasma leptin and IGF-I concentrations were measured in seven male volunteers after acute exercise to exhaustion using the Bruce protocol. Leptin concentrations declined following exercise reaching nadir values 30-120 min after exercise. As anticipated, plasma IGF-I concentrations showed a transient rise immediately after exercise falling thereafter to nadir levels 60-90 min after exercise before returning towards baseline levels. In view of the previously described decline in gonadotropin release after acute exercise, the decline in plasma leptin levels, perhaps related to the rise in IGF-I, may play a role in exercise-induced inhibition of gonadotropin release presumably by inhibition of GnRH secretion.

Adult↗

Oleanane triterpenes from Junellia tridens.

Three novel triterpenes, 3,4-seco-olean-12-ene-3,28-dioic acid (4), 3alpha-hydroxyolean-11-en-28,13beta-olide (5), and 3alpha-hydroxyoleane-11:13(18)-dien-28-oic acid (6), were isolated from the aerial parts of the Argentinean shrub, Junellia tridens. Another five compounds-oleanolic (1), oleanonic (2), and epioleanolic acids (3), all biosynthetically related to the three new oleananes, and epibetulinic acid (7) and sitosterol (8)-were also isolated. Structures were elucidated primarily by 1D and 2D NMR and mass spectrometry, and all protons and carbons of the three novel compounds were fully assigned by NMR. We report the minimum inhibitory concentrations of these compounds against Mycobacterium tuberculosis and conclude that they are responsible for antitubercular activity originally observed in the crude plant extract. LC-MS data is provided on the occurrence of triterpenes 1-6 in six other species of Junellia.

Magnetic Resonance Spectroscopy↗

Clonazepam and sertraline: absence of drug interaction in a multiple-dose study.

Thirteen subjects (seven men, six women) completed a placebo-controlled, randomized, double-blind, crossover study to determine whether an interaction occurs between clonazepam and sertraline. Ten days of once-daily doses of either clonazepam 1 mg and placebo (CZ + PL) or clonazepam 1 mg and sertraline 100 mg (CZ + SR) were administered; there was an 11-day washout period. Sertraline did not significantly affect the pharmacokinetics of clonazepam (p > 0.13). Clonazepam apparent oral clearance, volume of distribution, and half-life were 3.9 +/- 0.2 L/hr, 233 +/-11 L, and 40.5 +/- 0.3 hours, respectively. The kinetics of the inactive metabolite 7-aminoclonazepam were marginally affected by sertraline, with a 21% decrease in the elimination half-life (p = 0.03) relative to CZ + PL and no significant difference between treatments in area under the curve or metabolite ratio. Card sorting (CS), digit-symbol substitution test (DSST), nurse-rated sedation scale (NRSS), and self-rated sedation scores were assessed four times daily on days -1 (PL + PL), 1, 4, 7, and 10. There were no differences between treatments in area under the effect curve or maximum observed effect for CS, DSST, or NRSS. Maximum impairment on all assessment days was low, with a less than 10% change from the drug-free values for CS and DSST. Despite higher clonazepam concentrations, predose (time 0) psychomotor and sedation scores did not differ among days -1, 1, 4, 7, and 10 or between treatments. These results in healthy volunteers indicate that sertraline does not affect the pharmacokinetics or pharmacodynamics of clonazepam.

Adult↗

Rhegmatogenous retinal detachment after laser-assisted in situ keratomileusis (LASIK) for the correction of myopia.

PURPOSE: To report a case series of rhegmatogenous retinal detachment (RRD) after laser-assisted in situ keratomileusis (LASIK) and its incidence at a mean of 24 months. METHODS: The clinical charts of patients who experienced RRD after LASIK were reviewed. Five refractive surgeons and 24,890 myopic eyes that underwent surgical correction of myopia ranging from -0.75 to -29.00 diopters (D) (mean, -6.19 D) participated in this study. RESULTS: Thirteen eyes from 12 patients developed RRD after LASIK. Rhegmatogenous RD occurred between 1 and 36 months (mean, 12.6 months) after LASIK. Eyes that developed RRD had from -1.50 to -16.00 D of myopia (mean, -6.96 D) before LASIK. Rhegmatogenous RD were managed with vitrectomy, cryoretinopexy, scleral buckling, argon laser retinopexy, or pneumatic retinopexy techniques. The incidence of RRD at a mean of 24 months after LASIK in this study was 0.05%. CONCLUSIONS: Rhegmatogenous RD after LASIK is infrequent. If managed promptly, good vision can result. No cause-effect relationship between LASIK and RD can be proved from this study, but the authors recommend that patients scheduled for refractive surgery undergo a thorough dilated indirect fundus examination with scleral depression and treatment of any retinal lesions predisposing them to the development of RRD before LASIK surgery is performed.

Adolescent↗

Relating induced changes in EEG signals to orientation of visual stimuli using the ESI-256 machine.

The focus of this study is to investigate the relations that exist between changes in the orientation of simple visual stimuli displayed to a subject and the induced changes in brain activity recorded as EEG signals. These signals are recorded using the Electric Source Imaging with 256 electrodes (ESI-256). The 256-channel EEG signals of four subjects were measured monopolarly. Each subject was stimulated visually for approximately 7.5 minutes. The stimuli consisted of a series of 300 images depicting four basic orientations of a simple graphical element: a white bar on a black background, with each one of the four orientations (horizontal, vertical, +45 degrees and -45 degrees) shown a total of 75 times in a random order. The notion of missing information under certain orientations is not addressed at this juncture. The EEG signals produced by each subject were recorded in a continuous mode using a sampling rate of 1 kHz. Pre-processing of the raw EEG data obtained consisted of epoching, exclusion of faulty electrodes, and reduction of electro-oculogram (EOG) noise due to eye blinks. Topographical maps displaying brain activities and their individual electrode recordings are used as two different means for assessing these changes. It is important to note that the simplicity of the visual stimuli was considered in view of the massive data collected for interpretation. Our goal is to observe and determine new measures that would allow for the quantification and interpretation of such EEG brain activities. Such findings might prove useful for the later use of more complex stimuli and the potential development of size and orientation independent algorithms in image processing.

Brain Mapping↗

Chemiluminescent detection of oxidants in vascular tissue. Lucigenin but not coelenterazine enhances superoxide formation.

Lucigenin-amplified chemiluminescence has frequently been used to assess the formation of superoxide in vascular tissues. However, the ability of lucigenin to undergo redox cycling in purified enzyme-substrate mixtures has raised questions concerning the use of lucigenin as an appropriate probe for the measurement of superoxide production. Addition of lucigenin to reaction mixtures of xanthine oxidase plus NADH resulted in increased oxygen consumption, as well as superoxide dismutase-inhibitable reduction of cytochrome c, indicative of enhanced rates of superoxide formation. Additionally, it was revealed that lucigenin stimulated oxidant formation by both cultured bovine aortic endothelial cells and isolated rings from rat aorta. Lucigenin treatment resulted in enhanced hydrogen peroxide release from endothelial cells, whereas exposure to lucigenin resulted in inhibition of endothelium-dependent relaxation in isolated aortic rings that was superoxide dismutase inhibitable. In contrast, the chemiluminescent probe coelenterazine had no significant effect on xanthine oxidase-dependent oxygen consumption, endothelial cell hydrogen peroxide release, or endothelium-dependent relaxation. Study of enzyme and vascular systems indicated that coelenterazine chemiluminescence is a sensitive marker for detecting both superoxide and peroxynitrite.

Acetylcholine↗

Antitubercular activity of pentacyclic triterpenoids from plants of Argentina and Chile.

Screening of plants from South America for antitubercular activity and subsequent assay-guided fractionation resulted in the isolation and characterization of several pentacyclic triterpenoids. The MIC values of 22 triterpenoids were determined using the radiorespiratory BACTEC assay and range from 8 microM to above 128 microM. The structure-activity relationships are discussed.

Antitubercular Agents↗

Newborn screening for human immunodeficiency virus infection in the Bronx, NY, and evolving public health policy.

New advances in the diagnosis and treatment of HIV infection continue to propel changes in public understanding of HIV infection and the administration of public health law. Over the past decade, New York State has moved from a policy of blind newborn screening for seroprevalence data to mandatory HIV testing as part of the statewide Newborn Screening (NBS) Program. A new statewide program of expedited HIV testing (48-hr turnaround results) of pregnant women and newborns (whose HIV status is unknown at the time of delivery) began in the summer of 1999. To better understand the impact this program might have on the patients who receive health care at Lincoln Medical and Mental Health Center (Lincoln Hospital), we evaluated our experience with the current NBS program prior to inauguration of the new expedited testing program. We evaluated the NBS program from February 1, 1997, to January 31, 1999, including total number of HIV-exposed/infected infants born, mother's HIV status (if known) at the time of delivery, amount of time between blood sampling and return of the test results to the Hospital, and medical follow-up of infants with positive newborn screening test results. This was a retrospective study of the NBS registry and the medical records of patients who receive primary health care from the Pediatric Immunology Service of the Department of Pediatrics at Lincoln Hospital. One hundred and four newborns were identified with positive-HIV antibody (HIV-Ab-positive), and 13 (12.5%) were confirmed to be HIV-infected by positive polymerase chain reaction (PCR) test of viral DNA. Sixty-five (62.5%) of the newborns with positive NBS screening test results were born to mothers who were known to be HIV-infected prior to delivery; 39 (37.5%) were unanticipated. Four (30%) of the 13 HIV-infected babies were born to mothers who were known to be HIV-infected prior to delivery, and 9 (70%) were born to mothers whose HIV status was unknown at the time of delivery. Eighty percent (80%) of HIV-Ab-positive infants continued to receive follow-up care at Lincoln Hospital. Relocation to other health-care facilities occurred as a result of parental choice or due to foster care placement. No babies were "lost" from the NBS program. The average time between sampling and receipt of results for all blood tests was 16 days (range 10 to 141). Nearly 40% of newborns who acquired HIV infection from their mothers were unanticipated because the mother's HIV status was unknown at the time of delivery. These unanticipated HIV-infected infants represent missed opportunities for prevention of maternal-to-child transmission of HIV infection and early therapeutic intervention for HIV-infected infants. The new expedited HIV-testing program for New York State will facilitate early diagnosis, prevention and treatment of the HIV-exposed/infected infant for whom maternal HIV status is unknown at the time of delivery.

Female↗

Synthesis and characterization of a new biotinylated gramicidin.

A new linear gramicidin analog bearing a biotinyl group grafted on C-terminal part was designed to study ligand-receptor interactions. The C-terminal alcohol in the native peptide was first replaced by an amino group. Then the peptide was synthesized on a polystyrene resin functionalized by the 2-chlorotrityl chloride following a biotinylation performed in solution. This new N'-biotinyl-(EDA)15-Gramicidin A was reconstituted in planar lipid bilayers and exhibited channel activities similar to those of natural gramicidin, with unitary conductance value about 30 ps in 1 M KCl. Furthermore this ionophore activity was quenched by addition of streptavidin in the surrounding medium. Our system is an outstanding tool for monitoring ligand-receptor interactions and could be used for designing a new biosensor.

Amino Acid Sequence↗