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Biomedical subjects

C Avila

Publications and source records attributed to C Avila.

At least 19 recordsLinked to original sources

RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides.

S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci by a range of environmental cues. We report here that receptor for AGE (RAGE) is a central cell surface receptor for EN-RAGE (extracellular newly identified RAGE-binding protein) and related members of the S100/calgranulin superfamily. Interaction of EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, and lymphocytes triggers cellular activation, with generation of key proinflammatory mediators. Blockade of EN-RAGE/RAGE quenches delayed-type hypersensitivity and inflammatory colitis in murine models by arresting activation of central signaling pathways and expression of inflammatory gene mediators. These data highlight a novel paradigm in inflammation and identify roles for EN-RAGEs and RAGE in chronic cellular activation and tissue injury.

Amino Acid Sequence↗

Evaluation of the human choroidal melanoma rabbit model for studying microcirculation patterns with confocal ICG and histology.

The aim of this study was to develop consistently focal elevated choroidal masses of human choroidal melanoma in immunosuppressed rabbits and to correlate the visualization of prognostically significant microcirculation patterns from confocal indocyanine green angiography with histologic microcirculation patterns. A human choroidal melanoma cell line (OCM1) was implanted in the choroid of 40 rabbit eyes using three different techniques: transscleral choroidal injection of a cell suspension, injection of a cell suspension in a surgically induced cyclodialysis cleft, and implantation of solid tumor fragments in a surgically induced cyclodialysis cleft. The rabbits were immunosuppressed with daily injections of Cyclosporin A to prevent host versus graft reaction. The eyes were studied weekly with indirect ophthalmoscopy and fundus photography to monitor tumor growth and indocyanine green angiography using a confocal scanning laser ophthalmoscope to identify microcirculation patterns in vivo and correlate these findings with the histologic demonstration of tumor microcirculation patterns. A tumor mass was identified by indirect ophthalmoscopy in 16 of the 40 implanted rabbit eyes (40%). Each of these tumors was confirmed histologically to represent a focal elevated choroidal mass. All 16 elevated choroidal masses grow in eyes in which solid tumor fragments were implanted. In total, a melanoma was identified histologically in 28 of the implanted 40 eyes (70%). In addition to the 16 eyes where the melanoma appeared as a focal elevated choroidal mass, 4 eyes contained a focal elevated mass in the sclera and 8 eyes contained a flat choroidal tumor. Histologically, microcirculation patterns were identified only in the 16 eyes with focal elevated choroidal masses. Confocal indocyanine green angiography imaged microcirculation patterns in 13 of these 16 eyes (81%). The surgical implantation of small solid fragments of human choroidal melanoma in immunosuppressed rabbit eyes provides the best method to consistently obtain focal elevated choroidal masses. These focal elevated choroidal masses resemble booth the localization and the growth pattern of choroidal melanomas in humans. In addition, they also contain microcirculation patterns similar to those seen in humans that are detectable with confocal indocyanine green angiography. The use of indocyanine green angiography with this animal model may be especially useful in designing and evaluating anti-microcirculation treatments directed at uveal melanoma.

Angiography↗

Fetal death after normal biophysical profile score: An eighteen-year experience.

OBJECTIVE: It was our goal to determine the false-negative rate of the biophysical profile, characterize an 18-year variation in the false-negative rate, examine the relationship between the last normal biophysical profile score and death, and compare the false-negative rate of 2 disparate populations. STUDY DESIGN: Biophysical profile scores of 86,955 patients at 2 medical centers were collected and recorded prospectively. All perinatal deaths occurring within 1 week of a normal score were similarly recorded. The annual false-negative rate, the cumulative false-negative rate, and the ratio of false-negative results in cases of subsequent fetal death to the perinatal mortality rate were calculated. RESULTS: There were 65 fetal deaths among 86,955 fetuses. Over an 18-year study period at one institution, the false-negative rate varied but not significantly. The cumulative false-negative rate was 0.708 per 1000 at one medical center studied and 2.289 per 1000 at the other center. The average interval between last normal score and fetal death was 3.62 days and did not vary significantly between the medical centers. CONCLUSIONS: False-negative results in cases of subsequent fetal death reflect events that are subsequent to the last normal test result. Fetomaternal hemorrhage was the single most identifiable fetal cause of false-negative results in cases of subsequent fetal death. The ratio of the false-negative rate in cases of subsequent fetal death to the perinatal mortality rate should be used as a more objective approach to reporting this value, because the false-negative rate likely reflects the underlying perinatal mortality.

False Negative Reactions↗

Acute modulation of albumin microvascular leakage by advanced glycation end products in microcirculation of diabetic rats in vivo.

Advanced glycation end products (AGEs) are nonenzymatic glycosylated adducts of proteins that accumulate in vascular tissue during diabetes and aging. The aim of this work was to study the role of AGEs and of the oxidative mechanisms in diabetes-induced changes in vascular permeability. Intravital videomicroscopy was used to study albumin microvascular leakage in cremaster muscle. The extravasation of a fluorescent macromolecular tracer (fluorescein isothiocyanate-albumin) was measured for 1 h and, after computer-aided image analysis, was expressed as variations of normalized gray levels (arbitrary units). Extravasation of the macromolecular tracer was much higher in diabetic rats than in control rats (slope of extravasation versus time increased by >100%, P < 10(-4)). This increase was significantly inhibited when we blocked AGEs binding to their endothelial receptor by intravenous bolus of soluble recombinant receptor to AGEs (rR-RAGE) (slope of extravasation versus time decreased by 19, 30, and 40%, for 0.5, 2.5, and 5.15 mg/kg rR-RAGE, respectively) or by a 6 mg/kg intravenous bolus of antibody against RAGE (slope decreased by 53%). Systemic injection of probucol (an antioxidant) also significantly inhibited the increase in the extravasation of the macromolecular tracer occurring in experimental diabetes (slope decreased by 51%, P < 10(-4)). These results strongly suggest that in experimental diabetes the interaction of circulating AGEs and endothelial RAGE mediates albumin micro-vascular leakage, possibly via AGE-RAGE-dependent enhanced oxidant stress.

Albumins↗

Metabolic and hormonal changes during aerobic exercise in distance runners.

A group of long-distance runners is studied in order to clarify aspects concerning neuroendocrine mechanisms regulating organic adaptation to maximum effort, with special interest in the function of the growth hormone in fat metabolism and the possible use of ketone bodies as an alternative source of energy. A test is designed on a treadmill with a gradient of 3% and progressive increases in speed of 2 Km/h every 10 min, starting at 6 Km/h, and continuing until exhaustion. Masks are worn to enable the breath by breath measurement of expired gases and the subjects are monitored electrocardiographically using V5. For blood sample collection an antecubital vein is catheterized with a system enabling the replacement of the blood volume extracted by means of perfusion with physiological saline solution, and the increasing concentration of hormones in the blood is evaluated. The results obtained, indicate that epinephrine as well as GH hormones increase significatively from 20 min of exercise in runners promoting changes from carbohydrates to lipids as fuels to carry out exercise. The concomitant variations in energy substrates support the former hypothesis of work. Moreover, the muscle could employ acetylCoA originating from acetoacetate as an alternative metabolic source of fuel during maximum effort.

Adipose Tissue↗

Effects of androgen therapy on prostatic markers in hemodialyzed patients.

We have prospectively studied the evolution of serum levels of the prostatic-specific antigen and prostatic acid phosphatase in 14 male hemodialyzed patients, receiving a cycle of nandrolone decanoate (200 mg intramuscularly, once a week, for six months) as treatment for anemia. Androgen administration did not produce significant increases in serum concentrations of both tumor markers (basal: 0.9 +/- 0.5 and 0.7 +/- 0.3 ng/ml; at six months: 1.3 +/- 1.1 and 0.8 +/- 0.7 ng/ml respectively). Only one patient had a value of prostatic-specific antigen over the normal range: 4.2 ng/mol at the sixth month period, with a rapid decrease after the withdrawal of androgens. All the remaining values of both markers were within the normal range. In another six patients undergoing a prolonged treatment with androgens (between 9 to 24 months), the serum levels of prostatic-specific antigen and prostatic acid phosphatase were within the normal range in all of them. Nandrolone decanoate administration does not induce increases in prostate tumor markers when it is used as treatment for anemia in hemodialyzed patients.

Acid Phosphatase↗

Cloning and sequence analysis of a cDNA for barley ferredoxin-dependent glutamate synthase and molecular analysis of photorespiratory mutants deficient in the enzyme.

The NH2-terminal sequences of ferredoxin-dependent glutamate synthase (Fd-GOGAT; EC 1.4.7.1) purified from barley (Hordeum vulgare L.) and Chlamydomonas reinhardtii (Dangeard), and of a barley peptide, were determined and the barley sequences were used to design oligonucleotide primers for the polymerase chain reaction. A specific 1.3-kilobase (kb) cDNA fragment specifying the NH2-terminal one-third of the mature barley polypeptide, was amplified, cloned and sequenced. The NH2-terminus of plant Fd-GOGAT is highly conserved and homologous to the NH2-terminus of the heavy subunit of Escherichia coli NADPH-GOGAT. Based on sequence homologies, we tentatively identified the NH2-terminal region of Fd-GOGAT as the glutamine-amidotransferase domain, which is related to the corresponding domain of the purF-type amidotransferases. The Fd-GOGAT cDNA clone, and polyclonal antibodies raised against the barley enzyme, were used to analyse four Fd-GOGAT-deficient photorespiratory mutants. Three mutants (RPr 82/1, RPr 82/9 and RPr 84/82) had no detectable Fd-GOGAT protein in leaves, while the fourth (RPr 84/42) had a small amount of cross-reacting material. Hybridization to Northern blots of total leaf RNA revealed that both RPr 82/9 and RPr 84/82 were indistinguishable from the parental line (Maris Mink), having normal amounts of a 5.7-kb mRNA species. On the other hand, RPr 82/2 and RPr 84/42 each contained two distinct hybridizing RNA species, one of which was larger than 5.7 kb, the other smaller. Using a set of wheat-barley telosomic addition lines we have assigned the Fd-GOGAT structural locus to the short arm of chromosome 2.

Amino Acid Oxidoreductases↗

Sexual behavior and status for human immunodeficiency virus type 1 among homosexual and bisexual males in Mexico City.

The authors examined sexual behaviors, the seroprevalence of human immunodeficiency virus type 1 (HIV-1), and condom use among 2,314 homosexual and bisexual men tested during 1988-1989 at the AIDS (acquired immunodeficiency syndrome) National Center in Mexico City. Bisexuals constituted 24% of the sample; the seroprevalence rate was lower for bisexuals than homosexuals (21 vs. 34%). In logistic regressions, HIV-1 seropositivity was independently related to age, education, pattern of insertive/receptive behavior in anal sex, lifetime number of male sex partners, having sex with someone with AIDS, homosexual versus bisexual behavior, and a history of condyloma. The same logistic regressions were found to fit bisexuals and homosexuals. The rate of HIV-1 was reduced in individuals who indicated always requiring their partners to use a condom when practicing receptive anal sex (1% of the total). The most common practice for both homosexuals and bisexuals was "mixed" behavior (i.e., both insertive and receptive anal sex); this was also the practice with the highest risk. Bisexuals practiced both vaginal and anal sex with women and reported little condom use. The substantial seroprevalence among bisexuals, their frequent sexual contact with women, and their low rate of condom use imply a continuing role as a bridge of infection to females. Whether this risk will lead to a sustained heterosexual epidemic remains to be determined.

Adolescent↗

Atelosteogenesis type II: sonographic and radiological correlation.

Atelosteogenesis type II is a lethal chondrodysplasia characterized by severe micromelia, spinal abnormalities, talipes equinovarus, and abducted thumbs and toes. We present a case diagnosed at 21 weeks of gestation in which antenatal sonographic and post-mortem radiological findings were correlated. The patient had a recurrence of this disorder in a subsequent pregnancy which was terminated at 15 weeks, supporting previous reports of an autosomal recessive inheritance pattern. The feasibility of diagnosing the following morphological features by prenatal ultrasonography is demonstrated: coronal clefts of the vertebral bodies, metaphyseal and epiphyseal abnormalities, spinal deviations such as cervical kyphosis and a horizontal sacrum, additional ossification centres in the pelvis, and preaxial deviation of the thumbs and toes. The differential diagnosis of this disorder from other skeletal dysplasias with similar features is discussed.

Abnormalities, Multiple↗

Tumor necrosis factor in preterm and term labor.

OBJECTIVE: Our objective was to determine if labor (term and preterm) and microbial invasion of the amniotic cavity were associated with changes in amniotic fluid concentrations of tumor necrosis factor. STUDY DESIGN: Amniotic fluid was retrieved by transabdominal amniocentesis from 269 women in the following groups: midtrimester (n = 38), preterm labor with intact membranes (n = 52), preterm premature rupture of membranes (n = 74), term in active labor (n = 84), and term not in labor (n = 21). Fluid was cultured for aerobic and anaerobic bacteria and for Mycoplasma species. Tumor necrosis factor was measured with a commercially available enzyme-linked immunosorbent assay validated for amniotic fluid (sensitivity 60 pg/ml). RESULTS: Amniotic fluid from pregnant women in the second and third trimesters who were not in labor did not contain tumor necrosis factor. Among women in preterm labor, 92.3% (12/13) of patients with a positive amniotic fluid culture had detectable tumor necrosis factor in the amniotic fluid (median 820 pg/ml, range less than 60 to 2340 pg/ml). In contrast, only 10.2% (4/39) of women with a negative amniotic fluid culture had detectable tumor necrosis factor. Histopathologic chorioamnionitis was found in all patients who had a positive amniotic fluid culture, and tumor necrosis factor was detectable in the amniotic fluid of all but one of these patients. Among women in active labor at term, 25% (21/84) had detectable tumor necrosis factor in the amniotic fluid. Tumor necrosis factor was detected more frequently in the amniotic fluid of patients with a positive amniotic fluid culture than in patients with a negative culture (46.6% [7/15] vs 20.2% [14/69], p = 0.047). Amniotic fluid concentrations of tumor necrosis factor were significantly higher in patients with preterm premature rupture of membranes, labor, and a positive amniotic fluid culture than in the other subgroups of patients with preterm premature rupture of membranes. CONCLUSION: Parturition in the setting of microbial invasion of the amniotic cavity is associated with activation of the cytokine network as demonstrated by the detection of tumor necrosis factor in human amniotic fluid.

Adult↗

Endothelin-1,2 levels are increased in the amniotic fluid of women with preterm labor and microbial invasion of the amniotic cavity.

The purpose of this study was to determine the effect of gestational age, labor, and microbial invasion of the amniotic cavity on amniotic fluid concentrations of endothelin-1,2. Amniotic fluid was retrieved by amniocentesis from 148 women: patients at term with and without labor, patients with preterm labor with and without intraamniotic infection, and women in the second trimester of pregnancy. Endothelin-1,2 was measured by a sensitive and specific radioimmunoassay. Immunoreactive endothelin-1,2 was detectable in all samples of human amniotic fluid. Advancing gestational age and spontaneous term labor did not result in changes in amniotic fluid concentrations of endothelin-1,2. Women with preterm labor and positive amniotic fluid cultures for microorganisms had higher amniotic fluid concentrations of endothelin-1,2 than did those without microbial invasion of the amniotic cavity (p less than 0.05). These results support a role for endothelins in the mechanisms responsible for preterm delivery associated with intraamniotic infection.

Adult↗

Infection and labor. VII. Microbial invasion of the amniotic cavity in spontaneous rupture of membranes at term.

OBJECTIVE: The purpose of this study was to determine the frequency, microbiologic characteristics, and clinical significance of microbial invasion of the amniotic cavity in women with premature rupture of membranes at term. STUDY DESIGN: Amniocentesis was performed in 32 women with term premature rupture of membranes and amniotic fluid cultured for aerobic and anaerobic bacteria and Mycoplasmas. RESULTS: The prevalence of positive amniotic fluid cultures was 34.3% (11/32). The most common isolates were Ureaplasma urealyticum, Peptostreptococcus sp., Lactobacillus sp., Bacteroides fragilis, and Fusobacterium sp. Clinical chorioamnionitis occurred only in one patient with a positive amniotic fluid culture. Her neonate had ophthalmitis. Three patients (9.4%) had endometritis. Among women who were delivered vaginally, those with a positive amniotic fluid culture had a significantly higher rate of endometritis than those with a negative culture (33% [3/9] vs 0% [0/20], respectively, p = 0.023). CONCLUSIONS: These data indicate that microbial invasion of the amniotic cavity occurs in approximately one third of patients with preterm premature rupture of membranes. Microbial invasion of the amniotic cavity is a risk factor for endometritis in women with term premature rupture of membranes.

Amnion↗

Ichthyotoxic diterpenoids from the Cantabrian nudibranch Chromodoris luteorosea.

Five spongian diterpenoids 2, 3, 6-8, previously found in sponges and nudibranchs from very distinct geographical areas, have been isolated from the Cantabrian nudibranch Chromodoris luteorosea. The terpenoids are mainly localized along the border of the mantle of the mollusk. All the diterpenoids are toxic to Gambusia affinis.

Animals↗

Neutrophil attractant/activating peptide-1/interleukin-8 in term and preterm parturition.

The neutrophil is the leukocyte most frequently recruited into the amniotic fluid in cases of microbial invasion of the amniotic cavity. Neutrophil attractant/activating peptide-1/interleukin-8 is a newly identified cytokine that is capable of inducing selective neutrophil chemotaxis and activation. The purpose of this study was to examine the relationship between amniotic fluid concentrations of neutrophil attractant/activating peptide-1/interleukin-8, microbial invasion of the amniotic cavity, and parturition (term and preterm). Amniotic fluid neutrophil attractant/activating peptide-1/interleukin-8 was measured with an immunoassay validated for human amniotic fluid (sensitivity 0.3 ng/ml). Fluid was obtained from women in the following groups: midtrimester (n = 38), term not in labor (n = 38), term in active labor (n = 67), and preterm labor with intact membranes (n = 62). Fluid was cultured for aerobic and anaerobic bacterial and Mycoplasma. Sterile amniotic fluid from most women in the midtrimester of pregnancy and women at term not in labor did not contain immunoreactive neutrophil attractant/activating peptide-1/interleukin-8. Microbial invasion of the amniotic cavity was associated with increased concentrations of neutrophil attractant/activating peptide-1/interleukin-8. The amniotic fluid of women with preterm labor and sterile amniotic fluid who had preterm delivery contained higher neutrophil attractant/activating peptide-1/interleukin-8 levels than did the amniotic fluid of women who responded to tocolysis and had delivery at term. Term parturition is associated with increased concentrations of neutrophil attractant/activating peptide-1/interleukin-8 in the amniotic fluid. We conclude that neutrophil attractant/activating peptide-1/interleukin-8 is part of the host response to microbial invasion of the amniotic cavity and that increased amniotic fluid availability of this cytokine occurs in term and preterm parturition.

Adult↗

Amniotic fluid white blood cell count: a rapid and simple test to diagnose microbial invasion of the amniotic cavity and predict preterm delivery.

The purpose of this study was to determine the value of amniotic fluid white blood cell count in the diagnosis of microbial invasion of the amniotic cavity. Amniotic fluid was retrieved by amniocentesis from 195 patients with preterm labor and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria, as well as for mycoplasmas. The prevalence of a positive amniotic fluid culture was 12.8% (25/195). Patients with a positive amniotic fluid culture had a significantly higher median amniotic fluid white blood cell count than did patients with a negative amniotic fluid culture (median, 6 cells/mm3; range, 0 to 11,000 cells/mm3 vs median, 320 cells/mm3; range, 1 to 4480 cells/mm3; p less than 0.0001). An amniotic fluid white blood cell count greater than or equal to 50 cells/mm3 had a sensitivity of 80% (20/25), a specificity of 87.64% (149/170), a positive predictive value of 48.78% (20/41), and a negative predictive value of 96.75% (149/154) in the detection of a positive amniotic fluid culture for microorganisms. Although the sensitivity of an amniotic fluid white blood cell count (greater than or equal to 50 cells/mm3) in the detection of microbial invasion of the amniotic cavity was greater than that of the Gram stain of amniotic fluid (80% [20/25] vs 48% [12/25]; p less than 0.05), the specificity was lower (87.64% [149/170] vs 98.8% [168/170]; p less than 0.05). However, 88% (15/17) of all patients with an amniotic fluid white blood cell count greater than or equal to 50 cells/mm3 and a negative amniotic fluid culture had a spontaneous preterm delivery. We conclude that the amniotic fluid white blood cell count is a sensitive, simple, and inexpensive test for the detection of microbial invasion of the amniotic cavity. An elevated amniotic fluid white blood cell count is a risk factor for preterm delivery.

Adult↗