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Biomedical subjects

J Arias

Publications and source records attributed to J Arias.

At least 37 records · Page 2Linked to original sources

Pretreatment characteristics and clinical outcome of acute promyelocytic leukaemia patients according to the PML-RAR alpha isoforms: a study of the PETHEMA group.

Of 167 newly diagnosed acute promyelocytic leukaemia patients, 83 patients were long (L)-form (50%), eight variable (V)-form (5%) and 76 short (S)-form (45%). The V-form and S-form groups presented a significantly higher percentage of patients with white blood cell counts > 10 x 10(9)/l (P < 0.05). The S-form cases displayed a significantly higher number of cases with M3v microgranular features (P = 0.005) and CD34 expression (P < 0.0001). There were no differences between the three isoforms in complete remission (CR) rate (overall CR 90%), but the 3-year disease-free survival was lower for V-form cases than it was for L- and S-form cases (62% vs. 94% and 89%, P = 0.056). We conclude that the V-form and S-form types are associated with some negative prognostic features at diagnosis. However, our data were only able to demonstrate an association with adverse prognosis in the V-form type and, moreover, as the number of cases was limited, needs to be confirmed in large, uniformly treated series.

Adolescent↗

In vivo target promoter-binding activities of a xenobiotic stress-activated TGA factor.

Xenobiotic chemicals induce the expression of nuclear detoxification genes. A full understanding of this protective response will require characterization of its transcriptional regulatory machinery. We describe here the use of a recently developed plant chromatin immunoprecipitation (ChIP) assay to define nuclear promoter targets of TGA1a, a tobacco basic/leucine zipper transcription factor whose activity is potentiated by herbicide-induced xenobiotic stress. TGA1a selectively binds as-1-type cis-elements, which regulate transcription of putative detoxification and defense genes. With ChIP, we show that endogenous TGA1a binds as-1-containing promoter sequences of two tobacco glutathione S-transferase genes, GNT1 and GNT35. This binding activity is strongly enhanced by xenobiotic stress, as is expression of these genes. In contrast, TGA1a apparently does not bind in vivo to functional as-1 elements in promoters of PR-1a and PG13, genes whose expression is insensitive to this stimulus. The findings here thus discriminate between a number of possible functional promoter binding sites for a trans-regulatory factor, within the context of a signal response pathway.

Antibodies↗

Value of a dipstick based on recombinant RK39 antigen for differential diagnosis of American visceral leishmaniasis from other sympatric endemic diseases in Venezuela.

A laboratory trial using recombinant rK39 dipsticks for differential diagnosis of American visceral leishmaniasis (AVL) from other sympatric endemic diseases which share similar clinic features (Chagas disease, malaria, schistosomiasis and toxoplasmosis) was conducted in Venezuela. The 100% specificity of the test previously obtained in other countries was confirmed. The use of this test at the primary health care level in Venezuela for a rapid diagnosis of active AVL cases, which may avoid deaths, is recommended.

Antigens, Protozoan↗

Neuro-immune-endocrine functional system and vascular pathology.

A new interpretation of the response to injury by the nervous, immune and endocrine system is proposed, in order to integrate biochemical knowledge into the respective clinical areas. The discovery that the signaling molecules of the classical nervous, immune and endocrine systems, that is, the neurotransmitters, cytokines and hormones, respectively, are expressed and perceived by the three systems, has enabled us to establish a functional concept of these systems. The hypothetical integration of different pathological processes in a functional response made up by three phases, the immediate or nervous, intermediate or immune and late or endocrine ones, makes it possible to consider that all of them represent different forms of expression of a functional response whose meaning is always the same, that is, inflammation. If the functions that characterize each one of these three phases represent the activity of the nervous, immune and endocrine systems, the biochemical knowledge could be integrated into the functional meaning of each system.

Endocrine Glands↗

Increased duodenal mucosa infiltration by mast cells in rats with portal hypertension.

BACKGROUND: Enteropathy characterized by vascular and inflammatory alterations in the submucosa and mucosa has been described in patients with portal hypertension. AIMS: To verify the theory of inflammatory etiopathogenesis in experimental portal hypertensive duodenopathy, a prehepatic portal hypertension model based on the development of a single and triple partial ligation of the portal vein was used in the rat. METHODS: Five rats in each group (male Wistar, 230-255 g) were subjected to single (group II) or triple (group III) partial ligation of the portal vein and then compared to 5 control animals (group I, no operation). The animals were sacrificed 6 weeks later to analyze the histological parameters of the duodenal mucosa and submucosa, i.e., number, diameter and area of submucosal vessels, density of mast cells and mitotic cells. Body, liver and spleen weights and collateral circulation type were also assayed. RESULTS: As was demonstrated by the collateral circulation in all of the animals, the partial portal ligation was successful. Compared to the controls, the number of vessels per microscopic field (25 +/- 3.16 vs. 18.60 +/- 1.52), their diameter (20.09 +/- 2.90 vs. 12.61 +/- 3.97 microm, p < 0.05) and consequently their total area (12,749.30 +/- 2,298.26 vs. 3,455.82 +/- 1,702.33 microm2) were increased in the animals with a single partial ligation (group II) as well as in animals receiving triple partial ligation (group III) (33 +/- 12.88, p < 0.05; 22.92 +/- 6.72 microm, p < 0.05 and 51,376.95 +/- 43,732.24 miccrom2, p < 0.05, respectively). In addition, the density of mast cells increased from 3.26 +/- 1.18 in controls to 10.74 +/- 1.47, p < 0.01 and 22.50 +/- 6.42, p < 0.01 in single and triple partial portal ligated animals, respectively. Mitosis was significantly induced in crypts of the duodenal mucosa of the single portal ligated animals (25.20 +/- 1.78 vs. 17.40 +/- 1.14, p < 0.01) but was inhibited in triple partial ligated animals (12.40 +/- 5.12, p < 0.05). Compared to controls, both groups of rats developed liver atrophy with a greater decrease in the liver/body weight ratio in the single (2.71 +/- 0.50%, p < 0.01) compared to the triple partial ligated animals (3.33 +/- 0.09%, p < 0.01). CONCLUSIONS: The correlation of the degree of portal hypertension with the vascular changes and mast cell density suggests that both the hypertensive state and inflammation may play a role in the development of portal hypertensive intestinal vasculopathy. The inverse relation of portal hypertension with liver atrophy and mitosis rate in the crypts of the duodenal mucosa has not been clarified and should be investigated in future studies.

Analysis of Variance↗

[Evaluation of immunity against Venezuelan equine encephalitis virus and dengue in the human population of San Carlos, the Almirante Padilla Island Municipality, Zulia State, Venezuela. 1996].

The Insular Municipality of Almirante Padilla, historically, has been affected by Venezuelan Equine Encephalitis (VEE) epidemics, that have occurred cyclically in the Paez, Mara and Almirante Padilla Municipalities of the State of Zulia. During the last epidemic outbreak (1995), the studies reported a great number of cases of VEE in humans, based on epidemiologic-clinical diagnosis; occupying this municipality, the first place in the attack rate by the virus. At the same time, Dengue has been defined as an endemic illness affecting different regions, whose etiologic agent has previously circulated in the studied zone. In order to evaluate the immunity acquired against these viruses, a serological study was conducted in San Carlos Island. Two hundred and ten blood samples were obtained at random, among individuals of an age range between < 1 and 69 years, with and without antecedents of viral illness symptomatology at the moment of the epidemic outbreak, occurred in 1995. The samples were classified according to sex and age, and analyzed through the test of ELISA for specific IgG antibodies against the VEE and Dengue viruses. From the total of the samples processed, 116 (55.2%) were positive for VEE, affecting uniformly all age-groups with a slight masculine predominance. Likewise, 88 cases (41.9%) were determined positive for Dengue virus, affecting mainly the group ranging from 10 to 19 years. These results let us suggest that the epidemic outbreak occurred in 1995 at the Almirante Padilla Insular Municipality, had a double nature with both viruses being involved in the etiology of febrile cases.

Adolescent↗

Cytochrome oxidase activity in splanchnic organs of portal hypertensive rats.

OBJECTIVE: Portal hypertension is characterized by hyperdynamic splanchnic circulation associated with the development of portosystemic portal collateral circulation. Since blood flow regulation mechanisms in the splanchnic organs can be metabolic, its metabolic capacity has been studied using the mitochondrial enzyme cytochrome C oxidase as histochemical marker. METHOD: Cytochrome oxidase was quantified with a histochemical technique in the liver, pancreas and small bowel of Wistar rats in the control group (n = 8) and in rats with portal hypertension by triple stenosing ligation of the portal vein (n = 9) at 28 days of evolution. RESULTS: All rats with portal hypertension develop portosystemic collateral circulation. In these animals, cytochrome oxidase activity increases (p < 0.01) in the liver (left lateral lobe, periportal zone: 91.81 +/- 5.18 vs. 86.03 +/- 2.82) exocrine pancreas (125.6 +/- 7.25 vs 117.57 +/- 6.43; p < 0.05) as well as in the mucosa (crypts) and duodenum serosa, jejunum and ileum while it decreases in the pericentral zone of the hepatic acinus and intestinal villi. CONCLUSION: Cytochrome oxidase is considered an endogenous marker of local tissular metabolic capacity, so that its increased activity in the small bowel mucosa, crypts, exocrine pancreas and visceral peritoneum may be a metabolic factor that induces splanchnic hyperdynamic circulation in short-term portal hypertensive rats.

Animals↗

Non-heart-beating donors from the streets: an increasing donor pool source.

BACKGROUND: Non-heart-beating donors have become a source for organ donation, especially kidneys. The emergency room and the critical care unit are the two sources for this kind of donor. Three years ago, our hospital began a policy of obtaining organs and tissues successfully from subjects who died in the streets. METHODS: We consider as potential organ donors people who die out-of-hospital, are less than 50 years old, with less than 15 min of asystolia without cardiac massage, with a known etiology of death, and without general contraindications for donating. After death diagnosis, the cadaver is taken to the hospital where an emergency room doctor certifies the death. Afterward, the cadaver is transferred to the operating room where a cardiopulmonary bypass is performed to preserve the organs while the legal aspects of donation go on. RESULTS: Up to now, 111 cadavers have been taken as non-heart-beating donors; 53 of them have been actual donors. The average time before arrival to the hospital was 68+/-2.64 min, and the average interval between cardiac arrest and the beginning of cardiopulmonary bypass was 111.33+/-7.09 min. We have obtained 105 kidneys, 12 livers, 84 corneas, and 31 pancreata for islets isolation as well as 49 long bones. Seventy-two kidneys were transplanted, with a probability of survival of 83% at 36 months. CONCLUSIONS: Our experience indicates that it is possible to obtain organs for transplant from donors who die in the streets and are brought to the hospital under strict selection criteria.

Cadaver↗

In vivo demonstration of an antithrombin effect of abciximab.

Abciximab prolonged the activated clotting time (ACT) in a post hoc analysis from the Evaluation of IIb/IIIa Platelet Receptor Antagonist 7E3 in Preventing Ischemic Complications trial and an in vitro study has suggested an antithrombin effect of platelet glycoprotein IIb/IIIa inhibition. The purpose of this study was to evaluate the in vivo effects of abciximab on ACT and thrombin generation. In 46 patients undergoing coronary intervention, 24 received heparin and abciximab (group I), whereas 22 received heparin alone (group II). All received the same dose (70 U/kg) of heparin. Heparin was given after a baseline ACT, and in group I, abciximab was administered after the 5-minute ACT. Serial ACTs were recorded at baseline, 5, 10, 20, and every 30 minutes thereafter and at the procedure's end. No intervention including balloon angioplasty was performed until after the 20-minute ACT. The prothrombin fragment F1.2 (Nm/L) was measured at baseline, 20 minutes, and at the end of the procedure. Before (baseline) heparin and at 5 minutes, ACTs were similar. Abciximab prolonged ACT by a mean of 34 to 64 seconds starting with the 10-minute ACT and extending to the 50-minute ACT (all p <0.01 vs heparin alone). There was a progressive decrease in the F1.2 with abciximab, and baseline minus end F1.2 was 0.12 +/- 0.02 in group I versus 0.05 +/- 0.04 in group II, p <0.05. These data indicate a significant in vivo effect of abciximab plus heparin in increasing ACT and decreasing F1.2, results that are consistent with an effect on reducing thrombin generation.

Abciximab↗

Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: vertical transmission of deletions and rarity of de novo deletions.

OBJECTIVE: To determine the prevalence and type of Yq microdeletions in 86 consecutive men that fathered 99 sons by intracytoplasmic sperm injection (ICSI) and to determine the incidence of vertical transmission and de novo deletions in these boys. DESIGN: Prospective clinical observational study. SETTING: Genetics laboratory associated with a university IVF unit. PATIENT(S): Eighty-six consecutive infertile men presenting to an IVF clinic and their 99 ICSI-conceived sons. Fifty of the 86 men (58%) had idiopathic seminiferous tubule failure (STF); the remainder had a variety of other clinical indications for ICSI. INTERVENTION(S): Collection of peripheral and cord blood samples. MAIN OUTCOME MEASURE(S): The Yq genetic status of fathers who underwent ICSI and of their sons by the presence or absence of 22 Y-specific markers covering the four azoospermia factor (AZF) subregions. RESULT(S): Yq deletions of the AZFd/c region were detected in two (6.9%) of 29 azoo- or severely oligospermic men with STF. Identical deletions were found in their respective sons. No de novo deletions were detected in the remaining 97 sons conceived by men without deletions. CONCLUSION(S): The detection of Yq deletions only in men with severe STF is consistent with previous studies, with the AZFd/c region being most commonly affected. This study demonstrates the vertical transmission of these Yq deletions through the use of ICSI and supports the notion that, in most cases, Yq deletions will be inherited by male offspring. The absence of de novo Yq deletions in the male offspring indicates that these events are rare following ICSI in men with both STF and other common male factor indications.

Fathers↗

[Expression of the adhesion molecule CD44v6 in infiltrating ductal carcinomas of the breast is associated with hormone dependence. Our experience with 168 cases].

In order to investigate the possible hormone-dependence of CD44v6 in human breast cancer, we assayed the concentrations of this isoform in the membrane fraction of 168 invasive ductal carcinomas (IDC) and in 26 normal breast tissue samples, 18 fibradenomas (FAD), 3 fibrocystic disease specimens (FD), 7 mucinous carcinomas and 4 medullary carcinomas using the ELISA method. The results were compared with those of the estrogen (ER) and progesterone (PR) receptors, pS2, tissue type plasminogen activator (t-PA), cathepsin D, epidermal growth factor receptor (EGFR) and c-erbB2/neu oncoprotein concentrations. Menopausal status, size of the tumor in the cases of cancers, axillary lymph node involvement, histologic grade, ploidy, cellular synthesis phase, multifocality and multicentricity were also considered as variables. The cut-off value for CD44v6-positivity was set at 5 ng/mg prt. membrane protein content. 64/138 (38.1%) infiltrating ductal carcinomas scored positive. This was significantly higher than for the normal breast tissue (0/26; p: 0.0001), similar to that seen in the FAD (3/18), fibrocystic disease (0/3), infiltrating mucinous carcinomas (4/7) and lobular (3/15) and significantly lower than for the infiltrating medullary carcinomas (4/4; p: 0.027). There were no significant differences with the other groups of tissues studied. Furthermore, CD44v6-positive IDC showed significantly higher concentrations of ER, PR and cathepsin D and lower (p: 0.051) concentrations of EGFR when compared to their CD44v6-negative counterparts. The significant coexpression of ER, PR and cathepsin D seems to indicate a possible role for hormonal regulation of CD44v6 expression while the role of pS2 and t-PA, estrogen related proteins, was very reduced.

Adenocarcinoma, Mucinous↗

[Clinico-biological impact of pS2 positivity in estrogen receptor negative-infiltrating ductal carcinomas of the breast].

UNLABELLED: The pS2 protein is regulated by estrogens, but it can also be expressed in hormone independent breast carcincomas. We have carried out the present study in order to analyze the clinical-biological impact of pS2 positivity (>2 ng/mg prt.) in negative estrogen receptors (< 10 fmol/mg prt.) infiltrating ductal breast carcinomas (IDC). MATERIAL AND METHODS: 97 negative ER-IDC have been included in our study. We established the doses of the cytosol levels of pS2, progesterone receptors (PR), cathepsin D, tissue -type plasminogen activator (t-PA) and hyaluronic acid (HA), as well as the levels of HA, epidermal growth factor receptor (EGFR), CD44v5 and CD44v6 in cell surface membranes. We also considered the menopausal status, histological grade, ploidy, cellular synthesis phase, tumor size, axillary lymph node involvement and the existence of distant metastasis. The same results were obtained when the progesterone receptor status was also considered. RESULTS: ER-/pS2+ IDC presented higher (p <0,05) PR, t-PA and HA cytosol level, as well as lower EGFR concentrations, S-phase > 7% and S-phase >14% and lower N+>10 percentages and aneuploidy. They were also more frequently CD44v6+. The same results were observed when the positivity of the progesterone receptors was considered. CONCLUSIONS: The above results lead us to consider that the positivity for pS2 in ER- IDC is associated with hormone-dependent parameters, good differentiation and lower cellular proliferation, which can explain a better clinical outcome.

Biomarkers, Tumor↗

Increased plasma levels of corticosterone and prolactin and decreased T3 and T4 levels in short-term prehepatic portal hypertension in rats.

Corticosterone, T3, T4, and prolactin serum concentrations at 24 hr (N = 10), 15 days (N = 10), and 45 days (N = 10) of postoperative (postop) evolution were assayed to study the neuroendocrine response to portal hypertension. A triple stenosing ligature of the portal vein was used as the surgical technique of portal hypertension. This technique does not produce mortality and causes a decrease in the serum concentrations of T3 (0.043 +/- 0.009 vs 0.55 +/- 0.08 ng/ml) and T4 (3.93 +/- 0.55 vs 4.65 +/- 0.67 microg/ml) and an increase in those of prolactin (28.61 +/- 20.20 vs 12.84 +/- 3.96 ng/ml) and corticosterone (397.50 +/- 64.17 vs 311.53 +/- 57.41 ng/ml) at 45 days postop. The T3, T4, prolactin, and corticosterone alterations are associated with a persistent increase of TNF-alpha and NO, whose serum concentrations at 45 days postop are, respectively, 1838.33 +/- 247.07 vs 48.89 +/- 8.75 pg/ml and 0.43 +/- 0.13 vs 0.19 +/- 0.01 mmol/ml. TNF-alpha and NO could mediate these hormonal alterations in the evolution of short-term portal hypertension in the rat; thus they are involved in the systemic neuroendocrine response that is induced by this injury.

Animals↗

A xenobiotic-stress-activated transcription factor and its cognate target genes are preferentially expressed in root tip meristems.

In plants, as-1-type cis elements and their trans-acting factors confer tissue-specific and signal-responsive activities to the promoters of several glutathione S-transferase (GST) genes. Regulation of as-1 is widely thought to involve trans-acting factors that belong to a family of basic/leucine-zipper 'TGA factors' that selectively bind this element. We have previously shown that TGA 1a, a highly conserved TGA factor of tobacco, enhances transcription through as-1 in response to xenobiotic-stress cues. To better understand the functional contribution of this transcription factor to the expression of as-1-regulated genes, we have studied its tissue- and cell-specific localization in tobacco seedlings. We show here that the relative amount of TGA1a transcripts expressed in roots and shoots correlate with the as-1-regulated, basal-level expression of a GUS transgene and two putative target GST genes. In situ hybridization of intact seedlings demonstrated that TGA1a and these GST genes are preferentially expressed in root tip meristems. Similar findings were made with a gene-specific probe for PG13, a homologue of TGA1a, demonstrating that both factors are likely to be present in the same root meristem cells. Furthermore, TGA1a protein was immunologically detected exclusively in the primary root and its meristem. Collectively, these studies suggest that TGA1a, and perhaps PG13, may contribute to the expression of GST isoenzymes, especially in root tip meristems. The biological significance of these observations is discussed.

Basic-Leucine Zipper Transcription Factors↗

A new technique for tying the surgeon's knot.

A technique for tying the surgeon's knot is explained. This is based on considering that the active hand has two clasps, an inferior one formed by the thumb and the ring finger, which fixes the distal end of the ligature, and another superior clasp formed by the index and middle finger, whose rotating mobility makes it possible to wrap the proximal tips of the ligature around them one or more times and then to grasp the distal end and pull it through the proximal loops.

Humans↗