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C Barrios

Publications and source records attributed to C Barrios.

At least 37 records · Page 2Linked to original sources

Detection of TP53 gene mutations in human sarcomas.

To determine the frequency and type of TP53 mutations in human sarcomas, we examined exons 5-8 of the TP53 gene in 48 sarcomas using single-strand conformation polymorphism (SSCP) analysis and direct sequencing. Nine tumours had mobility-shifts on SSCP analysis, and sequencing of six of these tumours revealed 10 mutations: one insertion, two deletions and seven point mutations (four transitions and three transversions). Four of these mutations resulted in frame-shifts, one in a truncated protein, four cases in mono-allelic point mutations and one case in an altered splice site. These data show that approximately 20% of sarcomas harbour TP53 gene alterations and illustrate a variety of TP53 gene mutation types.

Base Sequence↗

Enhanced endothelium-dependent vasodilation in patients with cirrhosis.

Experimental evidence indicates that an increased production of nitric oxide could play a role in the peripheral vasodilation of portal hypertension. To test this hypothesis in humans, we studied basal serum NO(2-) + NO3- levels and the response of forearm resistance vessels to increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine infused into the brachial artery of 12 cirrhotic patients and 10 controls. Forearm vascular resistance (FVR) was calculated from mean arterial pressure and forearm blood flow (FBF). Cirrhotics showed higher NO(2-) + NO3- levels (P < 0.05), higher FBF (P < 0.01), and lower FVR (P < 0.01) than controls. The reduction of FVR in response to every dose of methacholine was greater in cirrhotics than in controls; this was significant (P < 0.05) at the 3 and 10 micrograms/min doses. This response to methacholine was not modified by blockade of vascular prostacyclin. The response to nitroprusside was similar in both groups. The increase in FVR in response to every dose of phenylephrine was significantly (P < 0.01) lower in cirrhotics than in controls. In cirrhotics, a significant correlation (r = -0.81, P < 0.01) was found between the FVR response to the highest doses of methacholine and phenylephrine. In conclusion, cirrhotic patients show an enhanced endothelium-mediated vasodilation, which suggests an increased synthesis of nitric oxide. This defect may mediate the peripheral vasodilation and hyporeactivity to vasopressors of these patients.

Adult↗

Changes in intraosseous pressure at the distal femoral epiphysis induced by variations in knee-joint position and intracapsular saline infusion. An experimental study in dogs.

Hemodynamic changes at the distal femoral epiphysis measured by recording intraosseous pressure (IOP) were investigated in mature and juvenile dogs after changes in knee-joint position and intracapsular infusion of 3 ml isotonic saline solution. Juvenile and mature animals responded to infusion test with a similar 5-fold increase in intracapsular pressure. A 2-fold increase in IOP was found when knee-joint flexion passed from 30 degrees to complete flexion. In juvenile dogs, IOP values were lower than in adults both in complete knee flexion and during infusion test. The similar response to joint hyperpressure tests observed in adult and juvenile dogs suggests that the barrier effect of the growth plate for epiphyseal venous drainage has no major influence in the hemodynamics of the distal femoral epiphysis.

Animals↗

Progressive opening-wedge osteotomy for angular long-bone deformities in adolescents.

We report the treatment in 17 patients of 27 angular deformities of the long bones by progressive opening-wedge osteotomy. The technique consists of percutaneous osteotomy and progressive angular correction using a modified Wagner distractor. Ten patients (20 bone segments) had adolescent bilateral idiopathic tibia vara with a mean angular deformity of 12 degrees varus (10 to 16). Seven other adolescent patients had secondary angular deformities either at the distal femur or the distal tibia. One of the femoral deformities had an associated 5.5 cm of shortening which was treated simultaneously. The patients with idiopathic tibia vara achieved a final mean angular correction of 15 degrees (mechanical axis from 12 degrees varus to 3 degrees valgus). In patients with secondary angular deformities the mean angular correction was 17 degrees. The Wagner device was removed in an average period of 12 weeks (9 to 27), and no major complications were observed. Progressive opening-wedge osteotomy is an alternative to conventional osteotomies for the treatment of angular deformities of the long bones in adolescent patients, and has the advantage of requiring less invasive surgery, allowing progressive and adjustable correction with bone lengthening if needed.

Adolescent↗

[Retrospective analysis of 80 cases of neonatal necrotizing enterocolitis].

We present the cases of necrotizing enterocolitis (NEC) treated in our hospital between 1980 and 1994, in order to analyze the risk factors that appear in the disease. We elaborate treatment and follow-up protocols. Prematurity, low birth weight and perinatal stress have a significant influence in NEC. Hemodinamic inestability, bloody stools, abdominal distension with decrease gastric outlet, along with significant radiological evidence in 90 percent of the cases, should rise suspition of NEC. We find fundamental the prevention of the disease in premature newborns with risk factors. Mean gestational age was 33 weeks. Prematurity was found in 87.5 percent of the patients, with a mean birth weight of 1683 g. Symptoms appeared at the age of 14 days. 32 percent of the cases were operated, 13 cases (16%) presenting with pneumoperitoneum, and a Mortality rate 15 percent. We treated 15 patients with colonic stenosis by resection and end-to-end anastomosis, with 6 percent mortality global mortality rate for NEC has been 28 percent.

Age Factors↗

c-myc oncogene amplification and cytometric DNA ploidy pattern as prognostic factors in musculoskeletal neoplasms.

The relationship between c-myc oncogene amplification in neoplastic cells as determined by means of Southern-blot analysis, and their nuclear DNA content as assessed by combined flow and image cytometry, was investigated in fresh tumor specimens from 33 patients with musculoskeletal neoplasms. Amplification, without rearrangement of the c-myc proto-oncogene, was detected in 4 out of 7 bone sarcomas and in 6 out of 26 soft-tissue sarcomas, but in none of 3 benign giant-cell bone tumors. Among the 10 cases with c-myc amplification, 2 were found to be cytometrically DNA diploid, 2 DNA tetraploid, and 6 DNA aneuploid. Conversely, there were 10 tumors displaying extremely aneuploid DNA patterns without c-myc oncogene amplification. Thus, there was no relationship between c-myc amplification and DNA ploidy; neither did the percentage of S-phase cells, as determined by means of image cytometry, correlate significantly with the occurrence of c-myc amplification. A surprising sex-bias was observed; all 6 cases of c-myc-amplified soft-tissue sarcomas occurred in females, whereas none of the 11 males with such sarcomas showed this amplification. When the clinical follow-up data of the patients were scrutinized, it was found that the DNA ploidy pattern of the neoplastic cell nuclei, in combination with the S-phase values, as well as the occurrence of c-myc amplification, yielded prognostic information, being statistically significant 2 years after the diagnosis.

Adolescent↗

No association between c-myc amplification and TP53 mutation in sarcoma tumorigenesis.

Oncogenes and tumor suppressor genes coparticipate in sarcoma tumorigenesis. We tested 43 sarcomas for c-myc amplification by Southern blot and molecular hybridization techniques and TP53 mutations by the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique and direct sequencing of the PCR products. We found eight tumors with c-myc amplification and five different tumors with TP53 mutations but no tumors harbor both c-myc and TP53 alterations. We suggest that c-myc amplification and TP53 mutations do not seem to coparticipate in the tumorigenesis of sarcomas.

Base Sequence↗

Octreotide prevents postprandial splanchnic hyperemia in patients with portal hypertension.

An increase in splanchnic blood flow is a physiological response to food intake. In patients with cirrhosis whose hepatic vascular resistance is already high, this increase in flow leads to marked increases in portal pressure. This study investigates whether octreotide prevents the increases in hepatic flow and portal pressure that follow the ingestion of a meal in patients with cirrhosis. Twenty-two patients with cirrhosis and portal hypertension were randomized to receive a mixed liquid meal (520 kcal) plus a single subcutaneous injection of either placebo or octreotide (200 micrograms). In the placebo group the ingestion of a meal was followed by an increase in the hepatic venous pressure gradient (+ 19.4 +/- 4.3%, p < 0.01) and hepatic blood flow (+ 38.2 +/- 14.6%, p < 0.05) at 30 min. In contrast, in the octreotide group eating caused no significant change in the hepatic venous pressure gradient (-2.8 +/- 3.6%, NS), while hepatic flow was decreased (-6.08 +/- 5.4%, p < 0.05). Octreotide blunted the postprandial increase in serum insulin and glucagon levels observed in the placebo group. In conclusion, in patients with cirrhosis and portal hypertension, octreotide prevents the postprandial increase in hepatic blood flow, and consequently also in portal pressure. These findings suggest that this drug could play a role in the long-term management of portal hypertension.

Blood Glucose↗

Clinicopathologic correlations and short-term prognosis in musculoskeletal sarcoma with c-myc oncogene amplification.

The prognostic significance of c-myc oncogene amplification was investigated in a series of 44 patients with musculoskeletal malignancy. There were 21 bone tumors and 23 soft tissue sarcomas. Amplification of the c-myc oncogene was detected in 11 tumors: 4 bone tumors and 7 soft tissue sarcomas. In 9 of the 11 myc-amplified tumors a high grade of malignancy was revealed histologically. The relative frequency of c-myc amplification was higher in grade IV tumors. After a mean follow-up of 18 months, 6 of 11 patients with c-myc-amplified tumors and 12 of 33 patients with nonamplified tumors either exhibited recurrence or died of tumor disease. Both 3-year estimated overall survival and disease-free survival probability were lower for patients with myc-amplified tumors. Amplification of the c-myc oncogene was associated with poor short-term prognosis. Although gene amplification was encountered sporadically in musculoskeletal sarcomas, the reported data suggest that analysis of c-myc may provide valid information on prognosis.

Adolescent↗

Specificity of antibodies induced after immunization of mice with the mycobacterial heat shock protein of 65 kD.

We have previously shown in mice and monkeys that mycobacterial heat shock proteins (hsp) of 65 and 70 kD exert a strong in vivo helper effect when conjugated to synthetic peptides or bacterial oligosaccharides and given in the absence of any adjuvants. Considering the degree of homology existing in the phylogeny among hsp belonging to the same family, we studied whether antibodies induced in mice with this protocol of immunization with the mycobacterial 65-kD hsp (hsp65) would cross-react, and to what extent, with hsp homologues from other origins, notably with the Escherichia coli GroEL protein and with the human homologue (hsp60). The results obtained show that antibodies to the mycobacterial hsp65 cross-reacted with the E. coli GroEL protein, both in ELISA and Western blot experiments, but not with the human hsp60. In competitive ELISA experiments, the binding of these antibodies to solid-phase hsp65 was very effectively inhibited by low concentrations of the mycobacterial hsp65; however, for human hsp60, 100 times higher concentrations were required in order to obtain similar patterns of inhibition. Finally, murine antibodies to the mycobacterial hsp65 always failed to give positive results in Western blot experiments using extracts of murine cells. Taken together, these data suggest that, after immunization of mice with the mycobacterial hsp65 conjugated to peptides or oligosaccharides in the absence of adjuvants, anti-hsp65 antibodies are induced which cross-react well with hsp homologues from other prokaryotes (e.g. E. coli GroEL), but which weakly bind the human hsp homologue. These results may have implications for the potential use of microbial hsp molecules in the design of conjugated vaccine constructs.

Animals↗

Heat shock proteins as carrier molecules: in vivo helper effect mediated by Escherichia coli GroEL and DnaK proteins requires cross-linking with antigen.

In the past few years we have shown that mycobacterial heat shock proteins (hsp) of 65 and 70 kD exert a very strong helper effect in mice and monkeys when conjugated to peptides and oligosaccharides and given in the absence of adjuvants. In the present study we show that this adjuvant-free helper effect (i) is not due to lipopolysaccharide (LPS), since it was observed in LPS-resistant mice (C3H/HeJ) immunized with hsp-based constructs containing the malaria peptide (NANP)40, and (ii) is characteristic of hsp, since it was not observed with conjugates containing the mycobacterial p38 antigen, which is not a stress protein. Interestingly, the hsp GroEL and DnaK of Escherichia coli, which share a high degree of homology with the mycobacterial 65-kD and 70-kD hsp, respectively, exhibit a strong in vivo helper effect when conjugated to the (NANP)40 peptide, and the conjugates given in the absence of adjuvants. This in vivo helper behaviour of the GroEL and DnaK proteins corresponds well to that observed with the mycobacterial 65-kD and 70-kD hsp, respectively, since the hsp65- and GroEL-based constructs require previous priming of the animals with live bacille Calmette-Guérin (BCG), which is not needed for the hsp70- and DnaK-based constructs. Finally, using both mycobacterial and E. coli hsp we show that their in vivo helper effect in the absence of adjuvants requires cross-linking to the synthetic peptide. Taken together, our results suggest that the adjuvant-free helper effect observed with mycobacterial and E. coli hsp may be a generalized phenomenon, exhibited by hsp from diverse microorganisms. These findings may find applications in the design of vaccine constructs.

Adjuvants, Immunologic↗

Determination of total mercury in scalp hair of pregnant and nursing women resident in fishing villages in the Eighth Region of Chile.

Total mercury (Hg-T) content in scalp hair of 59 pregnant and nursing women-with normal to high fish and seafood consumption-resident in fishing villages distributed throughout the coastal zone of the Eighth Region of Chile, and of 7 pregnant and nursing women-with negligible or no fish and seafood consumption-resident in a town located inland (Pinto) in the same region, was determined. Hair samples were collected, washed and stored according to IAEA recommendations, and were wet-digested in sealed Pyrex ampoules prior to the determination of Hg-T by gold amalgamation cold-vapour atomic absorption spectrometry. The absolute detection limit was estimated as 0.13 +/- 0.01 ng Hg-T (3 x sigma B1). Accuracy and precision were assessed with the aid of various biological and environmental certified and standard reference materials including human hair, and were satisfactory for ppm and sub-ppm Hg-T. Instrumental neutron activation analysis was used as a reference method for external quality control. The Hg-T content in hair of the study group (2.06 +/- 1.45(8) mg/Kg) was significantly higher than that of the control group (0.43 +/- 0.18(4) mg/kg) (p = 0.0001). These results were characterized according to geographical location, fish and seafood consumption, age and residence period in the fishing village.

Adolescent↗

Large experimental segmental bone defects treated by bone transportation with monolateral external distractors.

Monolateral frames were applied to five dogs and ten lambs for treatment of large segmental bone defects (LSBD) surgically induced in one of their femoral diaphyses. Reconstruction was attempted by bone transport, as developed by Ilizarov. Monolateral frames were used to minimize the draw-backs of Ilizarov's circular device. Radiographic, computed tomographic, and histologic studies were performed. The skin and soft tissues were not a major obstacle for the longitudinal migration of the screws during bone transport. Four months after the operations, healing and remodeling of the bone defect was always satisfactory. Histologically, the repair of the lengthened segment followed an intramembranous ossification pattern in its central areas and in the periphery as well. At the end of the experiment, the new induced bone had a virtually normal diaphyseal bone appearance. Bone transport for the treatment of experimental LSBD can be completed in monolateral frames.

Animals↗

Amplification of c-myc oncogene and absence of c-Ha-ras point mutation in human bone sarcoma.

The genomic organization of four oncogenes, c-myc, c-myb, c-Ha-ras, and v-fms, was analyzed in 21 patients with malignant bone tumors. Amplification of the c-myc proto-oncogene without rearrangement was the sole abnormality detected in four tumors: two chondrosarcomas, one osteosarcoma, and one lymphoma of bone. DNA hybridizations with c-myb, c-Ha-ras, and v-fms probes disclosed no structural gene abnormalities. Point mutations at the 12th codon of the c-Ha-ras gene were investigated with the polymerase chain reaction technique; no alterations were detected. The observed amplification of the c-myc there was not related to histologic type, grade, surgical stage, or ploidy level of the tumors. The results indicated that c-myc amplification, presumed to be involved in the development of malignancy in a variety of solid tumors, is encountered sporadically in malignant bone tumors; however, this occurs without relation to common histopathologic features. The clinical significance of oncogene amplification in bone sarcoma remains to be established.

Adolescent↗