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Biomedical subjects

A Flores

Publications and source records attributed to A Flores.

At least 55 records · Page 3Linked to original sources

Gain of function properties of mutant p53 proteins at the mitotic spindle cell cycle checkpoint.

Mutations in the p53 tumor suppressor gene locus predispose human cells to chromosomal instability. This is due in part to interference of mutant p53 proteins with the activity of the mitotic spindle and postmitotic cell cycle checkpoints. Recent data demonstrates that wild type p53 is required for postmitotic checkpoint activity, but plays no role at the mitotic spindle checkpoint. Likewise, structural dominant p53 mutants demonstrate gain-of-function properties at the mitotic spindle checkpoint and dominant negative properties at the postmitotic checkpoint. At mitosis, mutant p53 proteins interfere with the control of the metaphase-to-anaphase progression by up-regulating the expression of CKs1, a protein that mediates activatory phosphorylation of the anaphase promoting complex (APC) by Cdc2. Cells that carry mutant p53 proteins overexpress CKs1 and are unable to sustain APC inactivation and mitotic arrest. Thus, mutant p53 gain-of-function at mitosis constitutes a key component to the origin of chromosomal instability in mutant p53 cells.

Animals↗

Cytotoxicity, apoptosis, and in vitro DNA damage induced by potassium chromate.

Cr(6+) is a known human cytotoxic and carcinogenic agent that requires intracellular reduction for activation. We have analyzed the cytotoxic and DNA binding properties of K(2)CrO(4) (Cr(6+)) in comparison with those of Cl(3)Cr (Cr(3+)). The results indicate that K(2)CrO(4) exhibits higher cytotoxicity than Cl(3)Cr in several human and murine cell lines. The cytotoxic activity of K(2)CrO(4) is also indicated by the fact that is able to produce cell killing through apoptosis in cisplatin-resistant cells transformed by H-ras oncogene. Moreover, in vitro DNA binding experiments show that, in the presence of ascorbate (the major intracellular reductant of Cr(6+)), K(2)CrO(4) induces both interstrand cross-links and strand breaks. Because the chromate anion is by itself unreactive toward DNA, these data suggest that the cytotoxicity of K(2)CrO(4) may be associated with the DNA binding of reactive intermediate chromium species resulting from reduction of Cr(6+).

Animals↗

A protein-protein interaction map of yeast RNA polymerase III.

The structure of the yeast RNA polymerase (pol) III was investigated by exhaustive two-hybrid screening using a library of random genomic fragments fused to the Gal4 activation domain. This procedure allowed us to identify contacts between individual polypeptides, localize the contact domains, and deduce a protein-protein interaction map of the multisubunit enzyme. In all but one case, pol III subunits were able to interact in vivo with one or sometimes two partner subunits of the enzyme or with subunits of TFIIIC. Four subunits that are common to pol I, II, and III (ABC27, ABC14.5, ABC10alpha, and ABC10beta), two that are common to pol I and III (AC40 and AC19), and one pol III-specific subunit (C11) can associate with defined regions of the two large subunits. These regions overlapped with highly conserved domains. C53, a pol III-specific subunit, interacted with a 37-kDa polypeptide that copurifies with the enzyme and therefore appears to be a unique pol III subunit (C37). Together with parallel interaction studies based on dosage-dependent suppression of conditional mutants, our data suggest a model of the pol III preinitiation complex.

Binding Sites↗

[Pneumonias in patients with malignant hemopathies. Their etiology, response to treatment and prognostic factors in 69 patients (88 episodes)].

BACKGROUND: To analyze the etiology, treatment response and prognostic factors in 88 episodes of pneumonia in patients with hematological malignancies diagnosed in one center during a period of 30 months. PATIENTS AND METHODS: 88 episodes of pneumonia in 69 adult patients were studied. Age, sex, hematological malignancy and its treatment, existence of neutropenia and hypogammaglobulinemia, administration of immunosuppressive agents, type (hospital or community-acquired) and localization of pneumonia, presence of respiratory failure and treatment response were reported. For etiologic diagnosis of pneumonias, cultures of blood, sputum, pleural fluid and bronchoalveolar lavage (BAL), as well as Legionella pneumophila, Aspergillus fumigatus and Streptococcus pneumoniae antigen detection in urine were performed. Univariate and multivariate analyses of prognostic factors for pneumonia evolution were carried out. RESULTS: The median age was 63 years. Acute leukemias (AL) were the predominant hematological malignancies. Microbiologic documentation was obtained in 40 (45%) of pneumonias. Fiberoptic bronchoscopy with BAL (71%) was the diagnostic procedure with highest yield followed by blood cultures (25%). Streptococcus pneumoniae (13) was the most frequent isolated pathogen, followed by Legionella pneumophila (6) and Pseudomonas aeruginosa (6). A significantly higher prevalence of Streptococcus pneumoniae was observed in community-acquired pneumonia. The overall mortality rate was 20%. Respiratory failure (p = 0.0009), existence of neutropenia (p = 0.0023), age equal or higher than 60 years (p = 0.012) and prolonged administration of immunosuppressive agents (p = 0.015) were the prognostic factors associated with unfavourable evolution of pneumonias in the multivariate analysis. CONCLUSIONS: The etiologic diagnosis of pneumonia in patients with hematological malignancies was only achieved in a half of cases. In our series, the high prevalence of Legionella pneumophila can be attributed to the special epidemiologic characteristics of our hospital. Prognostic factors of pneumonia are related to individual factors as well as to the hematological status of patients.

Adolescent↗

Value of intravascular ultrasound in the assessment of coronary pseudostenosis during coronary interventions.

Coronary pseudostenosis (PS) are increasingly visualized during coronary interventions. In many patients PS are readily recognized by a characteristic angiographic pattern, but in other cases the diagnosis remains difficult. The value of intravascular ultrasound (IVUS) in the study of PS remains unknown. In this study, IVUS was used to assess the morphologic appearance of the vessel wall in 10 consecutive patients showing images of PS during coronary interventions. Mean age of the group was 60+/-12 years and two patients were female. IVUS was performed with a motorized pullback system to assess lumen, plaque, and total vessel cross-sectional areas. Measurements were performed both at the site of PS and at the distal reference segment. PS were always located on angled coronary segments. In one patient no lumen narrowing was detected with IVUS at the site of PS. In the remaining nine patients, however, a very localized elliptic-shaped lumen narrowing was demonstrated. As compared with the distal reference segment, coronary lumen (6.3+/-2.2 vs. 12.7+/-4.8 mm2, P < 0.001) and total vessel area (11.9+/-3.3 vs. 16.1+/-6.1 mm2, P < 0.05) were smaller at the site of PS. Severe lumen asymmetry was also documented at this site. In addition, a characteristic image of a flattened, three-layered wall, overlying a hypoechogenic space, was visualized in five patients. This unique pattern was considered the correlate of a partial coronary intussusception. PS induced some resistance to the advancement of catheters in two patients and temporary flow impairment in two additional patients. However, in every case, the image of PS disappeared once the guidewire was removed. Thus, at sites with PS, IVUS allows ruling out severe atherosclerosis and coronary dissections. In addition, IVUS also provides important diagnostic clues, including the image of intussusception, for making the correct diagnosis of this benign entity.

Aged↗

[D/D genotype of the gene for angiotensin converting enzyme as a risk factor for post-stent coronary restenosis].

INTRODUCTION: Although intracoronary stenting has decreased restenosis rate compared to percutaneous balloon angioplasty, still a high number of patients develop in-stent restenosis, which is an entity primarily due to tissue proliferation. Experimental studies have indicated that the renin-angiotensin system is involved in neointimal hyperplasia. Plasma and cellular levels of ACE are associated with an I/D polymorphism in the ACE gene. Indeed, DD subjects have the higher ACE levels. The purpose of this study was to explore the possibility that the I/D polymorphism might be related with in-stent restenosis. METHODS: We studied the ACE polymorphism in 48 consecutive patients who underwent successful implantation of an elective coronary stent in native coronary vessels and had a 6 month angiographic follow up. Restenosis (50% of the reference vessel) was observed in 23/48 patients. Patients with or without restenosis did not differ in demographic or clinical variables like diabetes, plasma cholesterol levels or in quantitative angiographic parameters such as vessel reference size or minimal lumen diameter after stent implantation. RESULTS: I/D polymorphism was distributed as follows: 22.9% of the patients were D/D; 14.5% were I/I and 62.5% of the patients were heterozygous I/D. The presence of restenosis was strongly related with the I/D polymorphism: 81.8% of the patients with D/D genotype had restenosis, compared with 40.0% of I/D patients and only 14.2% of the I/I patients (chi 2 p < 0.01). CONCLUSIONS: In this limited cohort, homocygous D/D of the ACE gene was significantly associated with in-stent restenosis, whereas restenosis was infrequent in patients with the I/I genotype.

Aged↗

Dominance, gender, and cardiovascular reactivity during social interaction.

Associations between trait dominance and cardiovascular reactivity were examined in previously unacquainted healthy men and women. Subjects participated in three mixed-gender dyadic interactions with the same partner while their cardiovascular responses were assessed. Among men, but not women, trait dominance was positively and significantly associated with systolic blood pressure reactivity. For men and women, diastolic blood pressure reactivity was positively and significantly associated with trait dominance while participants prepared to interact and with partner's trait dominance while they interacted. All effects held after controlling for trait hostility. Dominance merits attention as a correlate of cardiovascular reactivity, a finding that parallels emerging patterns in the cardiovascular disease literature. Gender and gender-related social factors as potential moderators of this relationship are discussed.

Adult↗

Higher lipid accumulation in broilers fed on saturated fats than in those fed on unsaturated fats.

1. Two experiments were conducted to assess the effect of fat sources differing in degree of saturation on the performance of and fat deposition in broiler chickens fed on isocaloric and isonitrogenous diets. 2. There were no differences in initial body weight between sexes but female broilers had lower daily gains (P<0.0001), final weights (P<0.0001) and food intakes (P<0.0001) than males. Abdominal fat pad weight was lower in male broilers than in female (P<0.001). 3. There were no significant differences in intake, weight gain, final body weight or food-to-gain ratios between birds fed on diets differing solely in the degree of fat saturation. Broilers fed on diets containing an animal fat blend or tallow had higher abdominal fat pad weight (P<0.001) and intramuscular lipid content (P=0.0085) than those fed on diets containing sunflower oil. 4. It was concluded that dietary fat saturation affects fat accumulation in broiler chickens.

Adipose Tissue↗

Effect of fatty acid saturation in broiler diets on abdominal fat and breast muscle fatty acid composition and susceptibility to lipid oxidation.

A total of 600 1-d-old Hybro N broiler chicks were randomly distributed into 24 litter pens and fed from 21 to 52 d of age isocaloric and isonitrogenous diets containing 8% of three different fat sources (tallow, lard or sunflower oil). Dietary treatment produced a significant effect (P < 0.05) in fatty acid composition of the intramuscular neutral lipids among all dietary treatments and for all lipid classes. A similar range of variation was obtained for abdominal fat fatty acid composition. In the intramuscular polar lipid fraction, dietary fat led to a narrow range in the variation of poly- and monounsaturated fatty acid composition, while the concentration of saturated fatty acids was maintained constant in all groups. A wide range in the melting point temperature of abdominal fat was observed (mean values of dietary treatments from 8.49 to 30.91 C), which indicates a major effect of dietary fatty acids on fat consistency. The variation of breast meat oxidation was small (mean values from 7.68 to 9.76 nmol malonaldehyde/mg protein). A dietary fat source rich in linoleic acid produces a marked effect on fat consistency, but only a moderately higher susceptibility to lipid oxidation of meat compared to tallow or lard.

Animal Feed↗

North-South twinning in paediatric haemato-oncology: the La Mascota programme, Nicaragua.

We describe the La Mascota twinning programme between La Mascota paediatric hospital in Managua, Nicaragua, and hospitals in Monza and Milan, Italy, and Bellinzona, Switzerland. The programme was based on the belief that an attempt to reduce the gap in mortality from cancer in childhood between developed and less developed countries should become an integral part of the care and research activity of a haemato-oncological department of a developed country and not simply an exercise in solidarity. This programme for acute lymphoblastic leukaemia shows that intellectual, organisational, and financial resources can be generated by a twinning programme. What is vital for such programmes is a long-term commitment to a comprehensive and holistic strategy that incorporates supply of drugs, training and supervision of health professionals, and the care of the children and of their parents.

Child↗

[Primary gastrointestinal lymphomas: response to eradicative therapy and prognostic factors in 52 patients].

BACKGROUND: To analyze the response to eradicative therapy and prognostic factors in 52 patients with primary gastrointestinal lymphoma (PGIL) diagnosed at a single institution in a 13 year period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the Working Formulation. Clinical stage was determined by the Ann Arbor system modified by Mushoff. The results of therapy as well as the influence of such characteristics on complete remission (CR), disease-free survival (DFS) and overall survival (OS) were studied. RESULTS: Mean age of the series was 53 years (SD 15). Thirty patients were males. HIV infection preceded PGIL diagnosis in 10 cases. Seventeen had bad performance status (ECOG 2-4) and 30 B symptoms. The PGIL localization was gastric in 31 cases and 29 had a low grade malignant lymphoma. B phenotype was demonstrated in 98% and 22 patients presented advanced stages (IIE2-IV). Treatment was radical surgery followed by intensive chemotherapy in 32 cases, intensive chemotherapy alone in 17, and surgical resection in 3. CR was obtained in 34 patients and 6 of them relapsed. The projected DFS from CR at 9 years was 72% and OS was 26%. CR and survival were not influenced by PGIL localization and treatment type. The main unfavourable prognostic factors were advanced stage (CR and OS), B symptoms (DFS and OS) and advanced ECOG score (CR, DFS and OS). Previous HIV infection had an independent prognostic influence on both CR and OS. CONCLUSIONS: In patients with PGIL, the achievement of CR, DFS and survival have been independent of the type of eradicative treatment used. Performance status, B symptoms and clinical stage have been the main prognostic factors. HIV infection carried an independent prognostic significance.

Adult↗

Comparative study of 2 variants of a modified esophageal transection in the Sugiura-Futagawa operation.

OBJECTIVE: To compare 2 techniques of esophageal transection in our modification of the Sugiura-Futagawa procedure for the treatment of bleeding portal hypertension in low-risk patients who cannot undergo surgery to have shunts placed. DESIGN: A prospective controlled trial comparing 2 variants of transection (classic, complete section of the anterior muscularis externa and whole mucosa; modified, placement of a circumferential running suture without opening the mucosa). SETTING: Academic university hospital. PATIENTS: Eighty-three low-risk patients (Child-Pugh score A and B) with a history of bleeding portal hypertension were operated on (35 classic, 48 modified transections) between 1989 and 1996. Both groups were comparable. MAIN OUTCOME MEASURES: Postoperative dehiscence of the transection was evaluated as well as fistulization, postoperative stenosis, rebleeding, postoperative endoscopic findings, survival, and mortality. RESULTS: Fistulization was observed in 1 (2%) of the patients in the modified group, and dehiscence in 1 patient (2%). In the classic group, 3 (8%) of the patients had dehiscence (relative risk, 2.6) and 1 (2%) of the patients, fistulization. No differences were observed regarding rebleeding (6 patients [6%] vs 5 patients [7%]), postoperative stenosis (4 patients [8%] vs 5 patients [10%]), postoperative endoscopic findings, survival, and mortality (early and late). CONCLUSION: The modified variant of the transection has a lower frequency of postoperative dehiscence, with the same long-term results.

Esophageal and Gastric Varices↗

Thermoluminescent response and relative efficiency of TLD-100 exposed to low-energy x-rays.

The dose-response of LiF:Mg,Ti (TLD-100) exposed to 15 and 35 kVp (8.0 +/- 0.1 and 8.1 +/- 0.1 keV effective energy respectively) x-rays and 60Co gamma-rays has been measured in the dose interval from (1.2-5.4) x 10(3) Gy for x-rays, and from 0.14 to 850 Gy for gamma-rays. In both cases the total TL signal and glow curve peaks 3 to 9 show supralinearity. The supralinearity function f(D) is similar for both x-ray beams, except for peak 8, where a 30% difference is observed. The maxima of f(D) for the total TL signal and peaks 5 to 8 are 2.1, 1.7, 6.4, 3.3 and 7.5 respectively for 8.1 keV x-rays and 3.7, 3.1, 13.6, 9.9 and 11.0 for gamma-rays. The measured relative efficiencies for x-rays with respect to 60Co, for the total TL signal and peaks 5 and 7, were 1.04, 0.97 and 3.2 respectively.

Aluminum↗

Effect of storage time and dietary enzyme on the metabolizable energy and digesta viscosity of barley-based diets for poultry.

The effect of barley storage time and dietary enzyme addition on the energy value of barley-based broiler diets was studied in two experiments. A two-rowed winter barley (Beka cultivar) was stored at room temperature for 0, 3, 6, 16, and 32 wk after harvesting. At these dates, diets were formulated using 50% barley with and without the addition of a commercial beta-glucanase-based enzyme product. In Experiment 1, 320 Arbor Acres chickens (eight replicates of three 10-d-old birds and eight replicates of one 30-d-old bird, per treatment) were fed the experimental diets to determine the AMEn following a 2 x 2 x 5 (age by enzyme by barley storage time) factorial design. At the end of the metabolism trial, viscosity of the intestinal contents was determined in 30-d-old broilers. Total beta-glucan, nonstarch polysaccharides (NSP), in vitro viscosity, and endogenous enzyme activity of barley grain decreased with increasing storage time. Dietary AMEn increased with barley storage time (from 2,755 to 2,939 kcal/kg DM, P < 0.001, for 0 and 32 wk of storage, respectively), with enzyme addition (2,861 vs 2,919 kcal/kg DM, P < 0.003), and with the age of animals (2,826 and 2,958 kcal/kg DM for 10- and 30-d-old chickens, respectively, P < 0.001). Interactions of enzyme and age by barley storage time (P < 0.02 and P < 0.001, respectively) were also detected. These data indicate that the minimum time of barley storage before its inclusion in broiler feed depends on the animals' age (more than 6 wk for 10-d-old chickens and 3 wk for 30-d-old chickens), and that the use of enzymes allowed a reduction in the time of barley storage. Digesta viscosity decreased with barley storage time (P < 0.001), and with enzyme addition (P < 0.001), an interaction of storage time by enzyme addition was shown (P < 0.007). Digesta viscosity was also negatively related to the dietary AMEn content (r = -0.68, P < 0.01). In vitro barley viscosity explained 53 and 90% of the variation in gut viscosity produced by unsupplemented and enzyme supplemented diets, respectively. In Experiment 2, the same diets as Experiment 1 and the barley grain were intubated into 120 adult roosters (Hy-Line) to determine TMEn. Dietary and barley TMEn values were not affected by barley storage time or enzyme addition (3,237 and 3,037 kcal TMEn/kg DM for diets and barley, respectively).

Animal Feed↗

Multiresistant Shigella species isolated from pediatric patients with acute diarrheal disease.

A total of 57 strains of Shigella (36 S sonnei, 21 S flexneri), isolated from children with acute diarrheal disease who presented for treatment at the Andes University Hospital, Merida, Venezuela, from June 1993 to June 1995, were tested for their susceptibility to trimethoprim, sulfamethoxazole, ampicillin, cefamandole, ceftriaxone, streptomycin, fleroxacin, and nalidixic acid, by the agar dilution method. Twenty-seven strains (75%) of S sonnei and eight strains of S flexneri (38.1%) isolates showed high-level resistance to trimethoprim (MIC90 > 1024 microg/mL), which was also associated with other resistance patterns. The most common resistant phenotype associated with trimethoprim-resistance among S sonnei isolates was sulfamethoxazole-streptomycin (63%); among S flexneri isolates, it was sulfamethoxazole-ampicillin-streptomycin (87.5%). Individual resistance was only observed for ampicillin, mainly in four isolates of S flexneri, and in one isolate of S sonnei. Most Shigella strains were resistant to three or more antimicrobial agents. These results confirmed that multiresistant strains of Shigella are present in Merida, and emphasize the importance to maintain these under surveillance in order to assess local susceptibility patterns and empiric therapy.

Acute Disease↗

Predicting forage indigestible NDF from lignin concentration.

We used chemical composition and in vitro digestibility data from temperate and tropical forages to develop relationships between indices of lignification and forage indigestible NDF. Neutral detergent fiber indigestibility increased nonlinearly as the lignin concentration of the NDF increased. Differences in estimated indigestible NDF using equations developed for a specific forage class (C3 and C4 grasses and legumes) were small and are probably not biologically significant when compared to those estimated from a common equation. Selected equations were compared with the Cornell Net Carbohydrate and Protein System (CNCPS) for the prediction of ADG. The linear equation (2.4 times NDF lignin content) used by the CNCPS and the Beef NRC had some of the largest errors due to mean bias. A log-log model [4.37 x (lignin/NDF)(.84)] provided the best combination of low total prediction error, low mean bias, and minimal error due to regression bias when permanganate lignin was used. A similar equation based on sulfuric acid lignin [6.17 x (lignin/NDF)(.77)] also met the above criteria. These equations then were evaluated with the CNCPS model against animal growth data from diets ranging in forage quality. Regardless of the equation used for predicting unavailable fiber, the CNCPS underpredicted daily gain, with mean biases ranging from -.10 to -.22 kg/d. Regression bias ranged from .13 to .14 kg/d and the coefficients differed from unity (P = .0001). The new equations gave numerically lower energy allowable ADG by steers compared to the linear equation currently used by the CNCPS model. The estimates were lower due to a higher predicted indigestible NDF, which resulted in a lower estimated forage energy value.

Animal Feed↗

Dengue virus in the brain of a fatal case of hemorrhagic dengue fever.

Neurologic complications associated with dengue fever are in general unusual. However, recent reports evidence more frequent neurologic alterations. In Mexico, neurologic involvement has not been reported in dengue cases. This report demonstrates the detection of dengue virus in the brain of a fatal case of dengue hemorrhagic fever. Serotype 4 was detected by immunohistochemistry and by RT-PCR in the inferior olivary nucleus of medulla and in the granular layer of cerebellum. Immunoreactivity was observed in neurons, astrocytes, microglia and endothelial cells. Our results emphasize the importance of neurologic manifestations in patients with dengue fever.

Adolescent↗