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Biomedical subjects

A Paez

Publications and source records attributed to A Paez.

At least 19 recordsLinked to original sources
PubMed2005

HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents.

Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-alpha or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-alpha treatment was very low (0.55 versus 9.87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.

Case-Control Studies↗
PubMed2004

Prostate cancer detection and tumor characteristics in men with multiple biopsy sessions.

PURPOSES: To address prostate cancer (PCa) detection with respect to the number of biopsy sessions performed, to identify risk factors for detection after a negative biopsy, and to analyze the clinical characteristics of the detected tumors. SCOPE: Only biopsied men (sextant) were included. A total of 1011 biopsy sessions were carried out in 770 men; 172 underwent a second prostate biopsy and 51 a third biopsy. During the first biopsy round, 111 cancers were found (14.4%), 27 in the second (15.7%), and five during the third round (9.8%), P=0.156. Only high-grade PIN or atypia were identified as independent predictors or PCa detection in subsequent biopsies (P=0.008). A nonsignificant increase of clinically localized tumors, and a decrease of metastatic and poorly differentiated cases were found when more biopsy sessions were needed for detection. CONCLUSIONS: A nonsignificant trend to lower cancer detection rates and less clinical relevance of the tumors detected can be observed when more biopsy rounds are needed for detection.

Adult↗
PubMed2004

Prostate apoptosis after doxazosin treatment in the spontaneous hypertensive rat model.

OBJECTIVE: To validate the spontaneous hypertensive rat (SHR) model for basic research into benign prostate hyperplasia (BPH), and to assess doxazosin-induced changes in prostatic structure and apoptotic status. MATERIALS AND METHODS: Four groups of rats were assessed: group 1, 15 SHRs treated with doxazosin; group 2, 14 SHRs with unilateral excision of the major pelvic ganglion; group 3, 14 untreated SHRs; and group 4, 16 intact Wistar-Kyoto (WKY) rats. The doxazosin mesylate (0.03 mg daily) was given compacted in rat food for 3 months. The prostatic ventral lobe (VL) was excised and weighed. Stereological light microscopy, multiplex reverse transcription-polymerase chain reaction of prostate caspases, and caspase-3 activity (cellular enzymatic assay) were assessed. RESULTS: There was more development of the glandular epithelium (P < 0.001) in SHR rats than in controls, which was even greater after doxazosin exposure (P = 0.027). SHR animals had higher caspase expression (P < 0.05) and activity (P = 0.008) than WKY rats, but both were reduced after doxazosin therapy (P < 0.01 and 0.028, respectively). CONCLUSIONS: This study confirmed prostate hyperplasia in the SHR model. Doxazosin exposure did not reduce the volume of glandular epithelium and contributed to protecting against caspase-induced apoptosis. The SHR model may be not a valid option to study doxazosin-induced apoptosis in BPH.

Analysis of Variance↗
PubMed2001

Prostate specific antigen density. Is there a role for this parameter when screening for prostate cancer?

The objective of this paper is to validate prostate specific antigen (PSA) density (PSAD) routine use to enhance PSA specificity in men with normal digital rectal examination and intermediate PSA values. It is a retrospective study of 235 men from a prostate cancer (PCa) screening program. All of them presented PSA values between 4 and 10 ng/ml, normal digital rectal examination, and a transrectal ultrasound (TRUS) guided biopsy available (PSA>/=4 ng/ml as the sole criterion for biopsy). Multivariate analysis failed to demonstrate higher PSAD values in men with PCa. PSAD cutoff points higher than 0.07 ng/ml per cc were considered as unacceptable, with less than 95% sensitivity. When a cutoff point of 0.15 was considered, as many as 30.6% of the cancers were missed. In conclusion we cannot recommend the use of this parameter for the above mentioned purpose.Prostate Cancer and Prostatic Diseases (2001) 4, 146-149.

Journal Article↗
PubMed2000

Growth, soluble carbohydrates, and aloin concentration of Aloe vera plants exposed to three irradiance levels.

Research was conducted on Aloe vera, a traditional medicinal plant, to investigate the effects of light on growth, carbon allocation, and the concentrations of organic solutes, including soluble carbohydrates and aloin. The plants were vegetatively propagated and grown under three irradiances: full sunlight, partial (30% full sunlight), and deep shade (10% full sunlight) for 12-18 months. After 1 year of growth, five plants from each treatment were harvested to determine total above- and below ground dry mass. Four plants from the full sunlight and the partial shade treatments were harvested after 18 months to assess the soluble carbohydrate, organic acid and aloin concentrations of the clear parenchyma gel and the yellow leaf exudate, separately. Plants grown under full sunlight produced more numerous and larger axillary shoots, resulting in twice the total dry mass than those grown under partial shade. The dry mass of the plants grown under deep shade was 8.6% that of plants grown under full sunlight. Partial shade increased the number and length of leaves produced on the primary shoot, but leaf dry mass was still reduced to 66% of that in full sunlight. In contrast, partial and deep shade reduced root dry mass to 28 and 13%, respectively, of that under full sunlight, indicating that carbon allocation to roots was restricted under low light conditions. When plants were sampled 6 months later, there were only minor treatment effects on the concentration of soluble carbohydrates and aloin in the leaf exudate and gel. Soluble carbohydrate concentrations were greater in the gel than in the exudate, with glucose the most abundant soluble carbohydrate. Aloin was present only in the leaf exudate and higher irradiance did not induce a higher concentration. Limitation in light availability primarily affected total dry mass production and allocation, without substantial effects on either primary or secondary carbon metabolites.

Journal Article↗
PubMed2000

Complex PTSD: a review of current issues.

The diagnostic formulation of PTSD has made a great advance since its inception in the early 1980s. Yet it may be argued that PTSD as now formulated does not go far enough in capturing the psychological response to traumatic events. The notion of "complex PTSD" is reviewed as an extension of the current formulations of PTSD. Complex PTSD transcends current formulations of PTSD in three main areas of disturbance: 1) complex symptom presentations, 2) characterological issues, and 3) vulnerability to repeated trauma. These issues are reviewed and support is provided for a formal recognition of "complex PTSD".

Humans↗
PubMed1999

The biosynthesis and post-translational modification of Pbs21 an ookinete-surface protein of Plasmodium berghei.

Radiolabelled methionine incorporation into synchronised Plasmodium berghei gametocytes or ookinete cultures, showed that Pbs21 is not synthesised in bloodstage parasites; synthesis was detected within three hours of induction of gametogenesis; synthesis was triggered at gametogenesis, not by fertilisation. We show native Pbs21 to be a hydrophobic membrane protein that was insensitive to cleavage by phosphatidylinositol phospholipase C (PI-PLC), but sensitive to alkaline hydroxylamine, and partially sensitive to glycosylphosphatidylinositol-dependent phospholipase D (GPI-PLD) and HNO2. 3H-myristic and palmitic acid, 3H-glucosamine and mannose incorporation indicated Pbs21 was acylated and glycosylated. Linkage of the acyl group was sensitive to HNO2, which released an acyl-phosphatidylinositol more hydrophobic than that released from P3 of Trypanosoma brucei. All these properties are consistent with the presence of a malaria-specific glycosylphosphatidylinositol (GPI) anchor. In contrast recombinant Pbs21 (rPbs21), expressed in Spodoptera frugiperda cells, was sensitive to both PI-PLC and GPI-PLD, consistent with the protein being modified by a different (S. frugiperda) GPI anchor. Brefeldin A blocked secretion of rPbs21 within a cytoplasmic reticular compartment. Following deletion of the putative GPI anchor addition site (amino acids 189 213), the protein was transported to the cell surface and secreted directly into the aqueous phase of the culture medium. Deletion of amino acids 205-213 disrupted Pbs21 processing, transport through the ER and distribution onto the cell surface. Deletion of amino acids 1-28 prevented transport of Pbs21 into the ER. This suggests that correct processing of the GPI anchor in the ER-Golgi network is essential for the successful secretion of the recombinant protein, which is additionally dependent upon an N-terminal secretory signal sequence.

Acylation↗
PubMed1999

Differential effect of estradiol on antibody secretion of murine hybridomas.

The need for increased antibody production by hybridomas has been approached by the addition to cell cultures of different growth factors; in vitro addition of estradiol-17beta (E2) to human blood lymphocytes increases the accumulation of plasma-blasts and Ig-secreting cells. Four different murine-murine hybridomas secreting different monoclonal antibodies (MAbs) were treated with E2. Specific antibody concentration was measured by enzyme-linked immunoadsorbent assay (ELISA) in culture supernatants whereas expression of E2-receptor in the hybridoma cells was determined by polymerase chain reaction (PCR). When E2 was added as a growth supplement to alpha-estrogen receptor positive murine-murine hybridomas it enhanced MAb secretion by as much as 255%, in a dose-dependant manner. This effect lasted for as long as the alpha-estrogen receptor was detected in the hybridoma cells, was inhibited by tamoxifen and was not observed in alpha-estrogen receptor negative hybridomas. The synthetic estrogen analogue diethylstilbestrol had no effect. Estradiol-17beta should be added to the list of hybridoma-inducing growth factors.

Animals↗
PubMed1999

Prostate specific antigen variation in patients without clinically evident prostate cancer.

PURPOSE: We address long-term within individual variation of serum prostate specific antigen (PSA) in men without clinical or biopsy evidence of prostate cancer. MATERIALS AND METHODS: We studied 943 men from a prostate cancer screening program with 2 PSA (PSA1 and PSA2) measurements available. A third PSA (PSA3) was obtained from 571 men. Only participants with no clinical evidence of cancer were included in the study. Within individual PSA variability was calculated based on indexes of percent coefficient of variation, ratio difference and PSA velocity. The relationship among these indexes, interval between measurements and number of PSA samples was assessed. RESULTS: Mean interval was 670.4 days between PSA1 and PSA2, and 801.8 days between PSA2 and PSA3 (p<0.001). Mean coefficient of variation was 18% after 2 and 15.7% after 3 PSA measurements. Mean ratio differences were -0.047 ng./ml. for 2 and 0.033 ng./ml. for 3 samples. Mean PSA velocity was -0.128 ng./ml. per year for 2 and -0.055 ng./ml. per year for 3 samples, with 95% confidence intervals of 0.634 and 0.315, respectively. Variability was higher if only 2 PSA measurements were done (p<0.001). No clear relationship was found between individual variability and interval between measurements. CONCLUSIONS: PSA velocity is within normal limits in almost all men (more than 95%) without clinically relevant prostate cancer. PSA individual variability is not fully dependent on the time between measurements when intervals are long, and can be substantially decreased with a third PSA sample.

Aged↗
PubMed1998

Differential tolerance is induced in T cells recognizing distinct epitopes of myelin basic protein.

Experimental allergic encephalomyelitis (EAE) is induced by T cell-mediated immunity to central nervous system antigens. In H-2u mice, EAE is mediated primarily by T cells specific for residues 1-11 of myelin basic protein (MBP). We demonstrate that differential tolerance to MBP1-11 versus epitopes in MBP121-150 is induced by expression of endogenous MBP, reflecting extreme differences in stability of peptide/MHC complexes. The diverse MBP121-150-specific TCR repertoire can be divided into three fine specificity groups. Two groups were identified in wild-type mice despite extensive tolerance, but the third group was not detected. Activated MBP121-150-specific T cells induce EAE in wild-type mice. Thus, encephalitogenic T cells that escape tolerance either recognize short-lived peptide/MHC complexes or express TCRs with unique specificities for stable complexes.

Animals↗
PubMed1997

Triggers of autoimmune disease in a murine TCR-transgenic model for multiple sclerosis.

The combination of genetic and environmental factors that contribute to human autoimmune responses has made potential triggers of these diseases difficult to identify. We examined how experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, is triggered using TCR-transgenic mice specific for myelin basic protein (MBP). In these TCR-transgenic mice, EAE can be actively induced and also occurs spontaneously. The incidence of spontaneous EAE in this model is largely confined to adolescence and early adulthood and is more prevalent among males than females, indicating that hormonal influences may contribute to triggering central nervous system autoimmune disease. Disease induction studies show that not all stimuli that activate MBP-specific T cells in vivo also induce EAE. Immunization with MBP peptide stimulates the transgenic T cells to produce Th1 cytokines; however, the activated T cells do not accumulate in the central nervous system and induce EAE unless pertussis toxin is also administered. EAE can be induced by intrathecal injection of either stimulated or nonstimulated transgenic T cells into nontransgenic or transgenic recipients. Therefore, gaining access to the central nervous system appears to be the critical step in this model for the induction of EAE, regardless of the activation state of the T cells.

Animals↗
PubMed1997

The influence of acute and chronic alcohol treatment on brain edema, cerebral infarct volume and neurological outcome following experimental head trauma in rats.

The aim of this study was to determine the influence of acute and chronic ethanol treatment on neurological outcome following head trauma in rats. Eight-two Sprague-Dawley rats were divided into 10 groups. Four groups received sham head trauma (surgical incision of the scalp but no trauma) and were treated with (A) nothing, (B) chronic ethanol (6% ethanol in drinking water for 40 days), (C) acute ethanol 1.5 g/kg, intraperitoneally (IP) and (D) acute ethanol 3 g/kg IP. Four groups (E-H) received the same treatment; in addition, head trauma was delivered using a weight-drop device to the left cranium (2 h after ethanol treatment in the acute ethanol groups). To assess the influence of acute plus chronic alcohol and whether the glutamate antagonist ketamine can modify the neurologic outcome following head trauma, two additional head trauma groups were studied: group I received both acute and chronic ethanol treatment and group J received acute ethanol (1.5 g/kg) IP plus ketamine (180 mg/kg). Neurologic assessment was performed at 1, 2, 4, 8, 10, and 24 hours after head trauma or sham trauma in all animals who survived the treatment (omitted in group J animals while still under the anesthetic influence of ketamine). At the end of 24 hours, or at the time of death, the animals were decapitated. Specific gravity was determined from brain tissues adjacent to the injury and the contralateral hemispheres and the volume of hemorrhagic necrosis was quantified. None of the rats in the sham trauma groups died or had neurologic deficits. Of the head trauma groups, the mortality in animals that received 3 g/kg of ethanol and the animals that received acute plus chronic ethanol treatment was 100% before the end of 24 hours. Fifty percent of the animals receiving low-dose acute ethanol treatment (1.5 g/kg) died before 24 hours. In contrast, the mortality in the other groups was only 30% (p < 0.05). The neurologic severity score was significantly higher (greater neurological deficit) in the surviving animals that received acute ethanol treatment at 10 and 24 hours than in rats receiving no ethanol or chronic ethanol treatment. Specific gravity was also lower in the acute ethanol-treated groups compared with no ethanol, chronic ethanol, and acute ethanol plus ketamine groups (p < 0.03). Based on these observations, we conclude that in this rat head trauma model acute ethanol treatment increases mortality, neurological deficit, hemorrhagic necrosis volume, and brain edema. On the other hand, chronic ethanol treatment has no apparent effect and ketamine treatment does not counteract the effect of acute ethanol treatment.

Administration, Oral↗
PubMed1997

Initiation and regulation of CNS autoimmunity.

Our studies addressed the questions of how self-reactive T cells escape tolerance and what stimuli cause these T cells to initiate autoimmune responses. We employed experimental allergic encephalomyelitis (EAE) as an animal model of multiple sclerosis (MS). Endogenous expression of myelin basic protein (MBP) induces tolerance in T cells that recognize one region of MBP, whereas T cells specific for a different region escape tolerance. Triggers of disease induction were investigated in a T-cell receptor (TCR) transgenic model in which the majority of T cells recognize the MBP epitope that does not induce tolerance. EAE occurs spontaneously in this model and the incidence of disease depends on microbial exposure. EAE can also be actively induced by immunization with MBP peptide accompanied by injection of pertussis toxin as well as by administration of pertussis toxin alone. Immunization with MBP peptide without pertussis toxin, however, stimulates the transgenic T cells, but the activated T cells do not accumulate in the central nervous system (CNS) or induce EAE. Our studies suggest that initiation of autoimmune disease involves complex interactions between the neuroendocrine system as well as the innate and specific immune systems.

Animals↗
PubMed1996

Epidural hemorrhage: is it abuse?

OBJECTIVE: To determine whether children presenting with epidural hemorrhage (EDH) are as likely to have been abused as are children presenting with subdural hemorrhage (SDH). DESIGN: Retrospective chart review. SETTING: Level I regional trauma center and a regional children's hospital. PATIENTS: All children at both institutions 3 years old or younger with a diagnosis of EDH or SDH identified by a search of the computerized trauma registry and hospital medical records from 1985 through 1991. MEASUREMENT AND RESULTS: Complete records were found for 93 of 94 eligible subjects. The diagnosis of accidental or inflicted injury was ascertained from the patient's hospital medical record or the records of Child Protective Services. Of all subjects (n = 93), 52% (48/93) were male and the median age was 15 months. Abuse was diagnosed in 47% (28/59) of children with SDH and 6% (2/34) of those with EDH. Other significant injuries were found in 47% of children with SDH and 18% of children with EDH. There was no statistically significant difference between the two groups with respect to the likelihood of identifying a skull fracture, the need for surgical evacuation of the hemorrhage, or mortality. CONCLUSIONS: Our data are consistent with current biomechanical concepts of intracranial injury. EDHs results from brief linear contact forces that commonly occur in unintentional falls. SDHs are caused by global high-energy rotational acceleration/deceleration forces that are commonly generated in episodes of abuse. Compared with SDH, EDH rarely results from abuse.

Acceleration↗
PubMed1994

Identification of a 20-kDa protein with calcium uptake transport activity. Reconstitution in a membrane model.

This paper presents results of experiments designed to further purify the membrane system involved in mitochondrial calcium transport. A partially purified extract, which transported calcium with a specific activity of 1194 nmol 45Ca2+/mg protein/5 min, was used to obtain mouse hyperimmune serum. This serum inhibited calcium uptake both in mitoplasts and in vesicles reconstituted with mitochondrial proteins containing cytochrome oxidase. Western blot analysis of the semipurified fraction showed that the serum recognized specifically two antigens of 75 and 20 kDa. Both antibodies were purified by elution from the nitrocellulose sheets and their inhibition capacity was analyzed. The antibody that recognized the 20-kDa protein produced a higher degree of inhibition than the other one.

Animals↗
PubMed1992

[High pressure filling bladder].

A complete urodynamic study was carried out on 41 consecutive patients presenting in the cystomanometry a vesical filling pressure at maximum capacity higher than 30 cm H2O. Two groups were evident: group I with neurogenic etiology, and group II without an obvious neurogenic etiology. From its results it can be seen that a diminished vesical accommodation is not a urodynamic fact restricted to vesicourethral neurogenic dysfunction, but it happens in several non-neurogenic conditions. Within the neurogenic group, the urodynamic element most frequently associated to a diminished vesical accommodation was an inferior motor neuron-like vesicourethral dysfunction. An increased vesical filling pressure was not enough to produce urinary incontinence, being also necessary an added factor to prompt involuntary loss of urine.

Adolescent↗