PubMed Health⌕ Search

Biomedical subjects

R Carrasco

Publications and source records attributed to R Carrasco.

At least 19 recordsLinked to original sources

Haploinsufficiency of the mSds3 chromatin regulator promotes chromosomal instability and cancer only upon complete neutralization of p53.

The mSin3 corepressor complex has been linked to diverse cancer signaling pathways through its capacity to regulate target gene expression via chromatin modification. mSds3, a cell essential gene, is a key component of the mSin3 complex serving to maintain its inherent histone deacetylase activity. mSds3 also serves an essential role in the establishment of pericentric heterochromatin, and genetic ablation of mSds3 results in chromosome missegregation. In contrast, mSin3A nullizygous cells show normal chromosome dynamics and cytogenetic profiles. The integral role of mSds3 in controlling chromosome segregation and mSin3-regulated transcriptional networks prompted efforts to determine the neoplastic impact of loss of one copy of mSds3 or mSin3A. In particular, we assessed whether loss of one copy of mSds3, alone or in combination with p53 mutation, results in aneuploidy and promotes a cancer-prone condition in the mouse. We observe that, in a p53 null background, loss of one mSds3 allele results in accelerated tumor onset and increased tumor burden. Notably, these mSds3(+/-) p53(-/-) tumors exhibit a more complex cytogenetic profile characterized by marked aneuploidy and centromeric associations. The presence of even one copy of p53 is sufficient to suppress the accelerated tumorigenesis in mSds3(+/-) mice, consistent with a key role for p53 in monitoring mitotic fidelity. These observations with Sds3 mutant mice contrast with mSin3A(+/-) p53(-/-) mice, which do not show an accelerated or increased tumor incidence relative to mSin3A(+/+)p53(-/-) controls, correlating with the absence of aneuploidy detected upon mSin3A genetic inactivation. This genetic study establishes that the capacity of mSds3 to cooperate with p53 deficiency in cancer predisposition relates to its specific role in chromosome segregation, rather than its central role in maintaining a functional mSin3A complex.

Animals↗

Ectoines as compatible solutes and carbon and energy sources for the halophilic bacterium Chromohalobacter salexigens.

AIMS: To investigate the catabolism of ectoine and hydroxyectoine, which are the major compatible solutes synthesized by Chromohalobacter salexigens. METHODS AND RESULTS: Growth curves performed in M63 minimal medium with low (0.75 mol l(-1) NaCl), optimal (1.5 mol l(-1) NaCl) or high (2.5 mol l(-1) NaCl) salinity revealed that betaine and ectoines were used as substrate for growth at optimal and high salt. Ectoine transport was maximal at optimal salinity, and showed 3- and 1.5-fold lower values at low and high salinity respectively. The salt-sensitive ectA mutant CHR62 showed an ectoine transport rate 6.8-fold higher than that of the wild type. Incubation of C. salexigens in a mixture of glucose and ectoine resulted in a biphasic growth pattern. However, CO(2) production due to ectoine catabolism was lower, but not completely abolished, in the presence of glucose. When used as the sole carbon source, glycine betaine effectively inhibited ectoine and hydroxyectoine synthesis at any salinity. CONCLUSIONS: The catabolic pathways for ectoine and hydroxyectoine in C. salexigens operate at optimal and high (although less efficiently) salinity. Endogenous ectoine(s) may repress its own transport. Ectoine utilization was only partially repressed by glucose. Betaine, when used as carbon source, suppresses synthesis of ectoines even under high osmolarity conditions. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is a previous step to the subsequent isolation and manipulation of the catabolic genes, so as to generate strains with enhanced production of ectoine and hydroxyectoine.

Amino Acids, Diamino↗

High resolution chromosome 3p, 8p, 9q and 22q allelotyping analysis in the pathogenesis of gallbladder carcinoma.

Our recent genome-wide allelotyping analysis of gallbladder carcinoma identified 3p, 8p, 9q and 22q as chromosomal regions with frequent loss of heterozygosity. The present study was undertaken to more precisely identify the presence and location of regions of frequent allele loss involving those chromosomes in gallbladder carcinoma. Microdissected tissue from 24 gallbladder carcinoma were analysed for PCR-based loss of heterozygosity using 81 microsatellite markers spanning chromosome 3p (n=26), 8p (n=14), 9q (n=29) and 22q (n=12) regions. We also studied the role of those allele losses in gallbladder carcinoma pathogenesis by examining 45 microdissected normal and dysplastic gallbladder epithelia accompanying gallbladder carcinoma, using 17 microsatellite markers. Overall frequencies of loss of heterozygosity at 3p (100%), 8p (100%), 9q (88%), and 22q (92%) sites were very high in gallbladder carcinoma, and we identified 13 distinct regions undergoing frequent loss of heterozygosity in tumours. Allele losses were frequently detected in normal and dysplastic gallbladder epithelia. There was a progressive increase of the overall loss of heterozygosity frequency with increasing severity of histopathological changes. Allele losses were not random and followed a sequence. This study refines several distinct chromosome 3p, 8p, 9q and 22q regions undergoing frequent allele loss in gallbladder carcinoma that will aid in the positional identification of tumour suppressor genes involved in gallbladder carcinoma pathogenesis.

Carcinoma↗

Effects of bensulfuron-methyl and cinosulfuron on growth of four freshwater species of phytoplankton.

The acute toxicity of sulfonylurea herbicides bensulfuron-methyl and cinosulfuron was tested on the five species of freshwater phytoplankton: Scenedesmus acutus, Scenedesmus subspicatus, Chlorella vulgaris and Chlorella saccharophila. Herbicide concentrations eliciting a 50% growth reduction over 96 h (EC50) ranged from 8 to 104 mg/l for cinosulfuron and from 0.015 to 6.2 mg/l for bensulfuron-methyl. The pesticides bensulfuron-methyl, atrazine and benthiocarb were more toxic than cinosulfuron, chlorsulfuron, molinate, fenitrothion and pyridaphenthion in a toxicity study with the same algal species. The transformation of effective concentrations of bensulfuron-methyl and cinosulfuron and other pesticides, obtained from toxicity measurements, into percent of the saturation level in water is used as a first evaluation of potential hazard to aquatic systems. The herbicides cinosulfuron, methyl-bensulfuron, atrazine and chlorsulfuron were more dangerous than the herbicides benthiocarb and molinate and than the insecticides fenitrothion and pyridaphenthion, in a study of hazard evaluation. The two species of Chlorella were more tolerant to both herbicides than the two species of Scenedesmus. A potential environmental hazard of sulfonylurea herbicides to aquatic systems has to be expected even at low environmental concentrations.

Environmental Exposure↗

Histological thin-sections: a method for the microscopic study of teeth in Spanish red deer (Cervus elaphus hispanicus).

A method to obtain thin histological sections (4-5 microm thick) from teeth, using a conventional microtome, is described for incisors, molars and canines from Spanish red deer (Cervus elaphus hispanicus). Decalcifying solutions of formic acid and nitric acid at different concentrations were ineffective. This was not the case for a solution of 14% hypochloric acid and polyvinylpyrrolidone (TBD-1(R) of Shandon). However, the time needed to complete decalcification was longer than the time estimated by other authors. Incisors required between 4 and 6 days, molars between 7 and 15 days, and canines between 8 and 12 days. The preparation of histological thin-sections from teeth with a conventional microtome, required some training or prior specialization, because most of defective or lost material occurred during the preliminary stage of the study. However this technique is inexpensive enough to be implemented in any histological laboratory. The preparations obtained are suitable for growth mark observation in dentine and in cementum for dating studies. Nevertheless, they are not suitable for enamel change studies, because the enamel is completely destroyed during the decalcifying process.

Age Determination by Teeth↗

Growth marks observation: preferential techniques and teeth for ageing of Spanish red deer (Cervus elaphus hispanicus).

A total of 207 teeth belonging to 53 deer (Cervus elaphus hispanicus) from Sierra Morena (South of Spain) were analysed using histological thin sections and/or polished thick sections. Growth marks were observed in dentine and cementum of incisors, molars and canines. Tooth, region of the tooth, and type of preparation giving the best performance in terms of sharpness and interpretation ease of the growth marks, when used for Spanish deer ageing, were identified. The tissue chosen for the study was the cellular cementum of the inter-radicular pad from molars and the acellular cementum of the root from incisors, both observed through longitudinal cuts. Histological sections obtained with a conventional microtome were optimal for a reliable identification of the first growth marks. In sections thicker than 15 microm the first rest line, when observed in cementum can be confused with the cementum-dentine junction; whereas in the polished sections from molars it will not appear at all. Dentine interpretation was more difficult. Its observation should only be accomplished using cross-sections of the molar root. Secondary or accessory marks were visible in every tooth, being those from the molar pad the easiest to distinguish. Canines were the less suitable teeth for this study.

Age Determination by Teeth↗

Laparoscopic pericystectomy for liver hydatid cysts.

BACKGROUND: The laparoscopic approach for managing of liver echinococcosis is a controversial issue because of scarce experience worldwide. The aim of this report is to describe the technical details of our laparoscopic method and present our results. METHODS: Consecutive cases of liver echinococcosis managed by laparoscopic surgery are reported. Thoracic x-ray and abdominal ultrasound had been performed previously. The following aspects were considered as selection criteria: unique cyst located in segments III, IV, V, VI, and VIII; diameter less than 7 cm; and no evidence of infection or calcification. An evacuating puncture was performed, germinative membrane removed, and pericystectomy performed, which extirpated the pericystic structure with the surrounding liver parenchyma. Specimens were removed in a plastic bag through one of the ports. Surgical morbidity, hospital stay, time until return to work, and evidences of hydatid recurrence were measured. RESULTS: Surgery was performed on eight patients (5 women and 3 men) with a mean age of 44.9 years (range, 22-83 years) who had a liver hydatid cyst with a mean diameter of 6.6 cm (range, 5-7 cm). During a mean follow-up period of 30 months (range, 23-44 months), no morbidity or hydatid recurrence were verified. Hospital stay was 2 days in all cases, and return to work was within 15 days. CONCLUSION: This laparoscopic technique, applied with selective criteria, can be a useful alternative for treating patients with liver hydatidosis because its results are comparable with those for open surgery studies involving similar follow-up time.

Adult↗

Treatment of proximal hypospadias with a tubularized island flap urethroplasty and the onlay technique: a comparative study.

BACKGROUND/PURPOSE: The onlay island flap urethroplasty was first described in the repair of mid and distal penile hypospadias. Since then, this technique has been increasingly used in more severe cases of hypospadias, because of the complications of tubularized flaps, mainly megaurethra and proximal anastomotic strictures. The aim of this study was to compare the morbidity of these 2 techniques. METHODS: Between April 1994 and December 1998, 80 patients underwent surgical treatment for hypospadias. A tubularized island flap (Ducketttechnique) was performed in 42 cases, and the onlay island flap technique was used in 38 patients. The authors retrospectively compared the complication rate and type of these 2 procedures. RESULTS: Altogether, fistula was the most frequent complication without any significant difference between the 2 groups (21.4% for Duckett technique and 18.4% for onlay repair; P > .05). However, the anastomotic stricture was much more common in the tubularized flap group (7.14% v 2.63%; P < .05). Moreover, a megaurethra was found only in the Duckett technique group (4.7%). There was no case of chordee recurrence, but 6 patients (15.7%) treated with the onlay technique required urethrolysis including dissection of the chord behind the urethral plate, and in the other 3 patients of the same group (7.9%), a dorsal Nesbit plication also was necessary. In all these cases, the urethroplasty included an island cutaneous flap to provide ventral coverage to the neourethra. CONCLUSIONS: The authors conclude that both techniques present similar complications. However, proximal strictures and megaurethra are more common after the Duckett technique. This procedure is of choice in patients with scrotal hypospadias. Conversely, the onlay repair should be completed with other procedures (urethrolysis, dorsal Nesbit plication) to obtain good results in patients with severe degree of chordee.

Child, Preschool↗

Effect of different doses of S-adenosyl-L-methionine on paracetamol hepatotoxicity in a mouse model.

This study investigated the hepatoprotective effects of N-acetylcysteine and different doses of S-adenosyl-L-methionine after a single intraperitoneal overdose of paracetamol in mice. Plasma concentrations of paracetamol metabolites were also determined. Female mice (Souris OFl strain) 16 weeks old and weighing 30 g were fasted for 18 h prior to intraperitoneal (i.p.) administration of 375 mg/kg (2.5 mmol/kg) of paracetamol. Experimental subgroups included mice administered paracetamol only (control group), those given of N-acetylcysteine 1 g/kg (6.13 mmol/kg) i.p. immediately after paracetamol overdose (T0) and 6 h after dosing (T6) and those administered S-adenosyl-L-methionine at doses of 20 mg/kg (0.05 mmol/kg) and 1 g/kg (2.5 mmol/kg) i.p. at T0 and T6. Twenty-four hours after paracetamol overdose, mortality and liver necrosis were significantly lower (p < 0.01) in mice treated with 2.5 mmol/kg of S-adenosyl-L-methionine and N-acetylcysteine at T0 as compared with the remaining subgroups. Plasma ALT concentrations were significantly lower (p < 0.01) in mice treated with 2.5 mmol/kg of S-adenosyl-L-methionine than in those given N-acetylcysteine. Plasma concentrations of paracetamol metabolites showed an increase in the glucuronide conjugate and a decrease in the mercapturic acid conjugate in N-acetylcysteine-treated mice and an overall decrease in the conjugation pathway without changes in the oxidative pathway in S-adenosyl-L-methionine-treated animals. We conclude that S-adenosyl-L-methionine at doses of 1 g/kg (2.5 mmol/kg) i.p. was equally effective as 1 g/kg (6.13 mmol/kg) N-acetylcysteine for preventing hepatotoxicity after paracetamol overdose in mice. S-adenosyl-L-methionine may be a therapeutic alternative to N-acetylcysteine as an antidote for poisoning with paracetamol.

Acetaminophen↗

Long-term follow-up of nineteen cystic lymphangiomas treated with fibrin sealant.

BACKGROUND: Surgical exeresis is regarded as the first choice treatment for cystic lymphangioma. Surgery may be extremely complex, giving rise to complications. Several therapeutic methods have been described to avoid the complications derived from the conventional surgical approach. The idea of treating lymphangioma by means of suction and injection of fibrin sealant (Tissucol), is an alternative to surgery. METHODS: The authors present 19 cases of cystic lymphangioma, treated with fibrin sealant injected into the lesion, during the 1991 to 1997 period. Two of the patients had been treated surgically and experienced recurrence of the tumor previous to treatment. In the other 17 cases, puncture was the only therapy applied. One patient required 3 punctures, another 6 patients required 2 punctures, and only 1 of them, after 2 unsuccessful punctures, was treated with surgical resection. The rest of the 10 cases subsided after the first puncture. Follow-up ranged between 3 and 72 months, with a mean of 40 months. RESULTS: The ultrasonographic (US) follow-up showed a complete remission in 17 patients treated with puncture. One patient remained with a small intermittent tumor, the appearance of which is related to catarrhal processes, and another patient rejected further puncture after the second one. No complications appeared. CONCLUSION: These results support the fact that the puncture, aspiration, followed by injection of Tissucol, is a choice in the surgical treatment of cystic lymphangioma.

Child, Preschool↗

Rapid surveys for program evaluation: design and implementation of an experiment in Ecuador.

This paper presents details from the field test of two rapid surveys in Ecuador in 1995. It focuses on how the surveys were designed and implemented, including descriptions of the sampling procedures, the preparation and use of preprogrammed palmtop computers for data entry, the selection criteria for the interviewing team, and how the training was designed. Lessons are drawn that will assist health professionals plan and carry out better rapid data collection in the future. The objective of the study was to evaluate the reliability and validity of data gathered during the rapid surveys as compared with a recent "gold standard" national survey. A two-way factorial design was used to control for differences in sampling (probability versus quasi-probability) and methods of data collection (paper versus palmtop computer). Few differences were detected between the surveys done on palmtops as compared to paper ones, but urban and rural differentials in contraceptive use were less pronounced in the rapid surveys than in the earlier, national survey. This suggests that caution should be exercised in interpreting the disaggregated data in these rapid surveys. In-depth interviews revealed two features of the rapid surveys that were especially popular: the palmtops for their speed of data entry, and the short questionnaire for its "low impact" on a respondent's time. The common belief that computers would disturb respondents was not found to be the case. Even with no computer experience, the interviewers rapidly mastered the new technology.

Adult↗

[Interferon treatment of giant hemangioma].

As many as 10% to 20% of patients with disseminated hemangiomas involving vital organs fail to respond to conventional treatment with steroids, radiotherapy, laser or cyclophosphamide. For the last years, interferon-alpha-2 has been successfully used to treat complicated giant hemangiomas, because of its ability to inhibit endothelial cell proliferation. We report the case of a 3-months-old infant presenting with a giant cervicofacial hemangioma with extension to the chest wall and larynx, causing episodes of severe respiratory distress. CT scan and MRI revealed a second vascular lesion measuring 24 x 16 mm in the liver. Initial treatment with corticosteroids (prednisolone at a dose of 1-3 mg/kg/daily) and endoscopic laser barely improved the symptoms and the patient presented more episodes of shortness of breath requiring admission to the ICU. Interferon therapy was started at a dose of 3 million units/m2/every other day and was continued for 9 months. At the completion of the therapy, there was complete regression of the hemangioma. Four months later, the patient is asymptomatic. No side-effects were presented for hyperthermia when the treatment was started resolved with antithermics. Blood tests were always within the normal range.

Facial Neoplasms↗

[Post-traumatic facial deformity. Globulomaxillary cyst].

The case of a child treated for globulomaxillary cyst is presented. He first consulted because of progressive deformity of the face and upper gum, starting several months before. He had a history of facial contusion at the time the deformity began.

Adolescent↗

The human cytomegalovirus IE2 86 kDa protein elevates p53 levels and transactivates the p53 promoter in human fibroblasts.

Human cytomegalovirus (HCMV), a herpesvirus, has previously been reported to elevate cellular p53 levels within infected human fibroblasts. Since this elevation was reported to be due to the expression of HCMV immediate early (IE) gene products within the fibroblasts, and the HCMV immediate early region encodes several predominant proteins, the identity of the protein responsible for this elevation was investigated. We report that the HCMV IE2 86 kDa protein was clearly found to be the major immediate early protein responsible for elevating p53 levels within the fibroblasts. We also report that the HCMV IE2 86 kDa protein was found to transactivate the p53 promoter 5-6 fold, thus explaining the 5-6 fold rate of increased p53 protein synthesis we find in the HCMV infected fibroblasts. Since transactivation of the p53 promoter was observed in IE2 86 kDa transfected as well as in HCMV infected fibroblasts, transactivation of the p53 gene, therefore, is part of the mechanism HCMV uses to elevate p53 levels in infected fibroblasts. This is the first report to implicate the HCMV IE2 86 kDa protein in the elevation of p53 levels in fibroblasts, as well as in the transactivation of the p53 promoter in these cells.

Cells, Cultured↗

Lipid peroxidation and antioxidants in newborns.

The aim of this investigation was to elucidate a possible correlation between lipid peroxidation, antioxidant concentrations and erythrocyte membrane fluidity in plasma from newborns. Ten healthy newborns were recruited. Venous blood samples were collected at birth, and thereafter at 3 and 72 h postnatal age. The following parameters were assessed: hydroperoxides, Coenzyme Q10 and alpha-tocopherol both in plasma and in erythrocyte membranes, and fluorescence polarization (as a tool for assessing membrane fluidity). Hydroperoxides were shown to be high in erythrocyte membranes at birth and significantly decreased at 3 and 72 h after birth. In the erythrocyte membranes, coenzyme Q10 content showed an opposite behaviour with respect to the plasma compartment. Membrane fluidity appeared unchanged even in the presence of the above mentioned modifications.

Antioxidants↗