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Biomedical subjects

A Costa

Publications and source records attributed to A Costa.

At least 217 records · Page 12Linked to original sources
PubMed1996

Image analysis for the evaluation of p53 expression in human cancers.

We compared the results of a subjective microscopic evaluation and an interactive image analysis of p53 expression in different human tumours. Expression of p53 was immunocytochemically detected by using the monoclonal antibody PAb 1801, and the evaluation was made blindly by two observers. Image analysis was performed on the same sections using DISCOVERY. The image was segmented into objects and background by interactive thresholding. Several morphological and densitometric features were selected in order to remove artefacts, lymphocytes, stromal cells and overlapping nuclei from the counting. The study was performed on series of 30 cases for different tumour types: breast, colon, oral cavity, ovary and lung cancer. Spearman's correlation coefficient ranged from 0.72 to 0.95 (P = 0.0001). Image analysis can therefore be considered as a quick and alternative approach to microscopic evaluation of nuclear immuno-determinations.

Antibodies, Monoclonal↗
PubMed1996

[Assessment of various new predictive parameters of the outcome of mechanical ventilation weaning].

OBJECTIVE: To evaluate new indexes predicting weaning outcome from mechanical ventilation. EXPERIMENTAL DESIGN: Prospective study with two main end-points: a comparison of weaning indexes between successful and unsuccessful groups and an evaluation of their predicting value. ENVIRONMENT: Surgical-Medical Intensive Care Unit. PATIENTS: Patients ventilated for more than 72 hours and subjected to a weaning trial until spontaneous ventilation. MEASUREMENTS: Traditional weaning parameters [respiratory rate (fsb), expiratory minute volume (Vesb), Maximal Inspiratory Pressure (MIP)] along with the new indexes [fsb/Vtsb) (rate to tidal volume ratio), CROP index (Compliance Rate Oxygenation Pressure), P0.1/MIP, IEQ (Inspiratory Effort Quotient), WI (Weaning Index)] were measured before discontinuation of ventilation support. RESULTS: A statistically significant difference was observed between successful and unsuccessful groups for the following parameters: fsb, MIP, fsb/.Vtsb, CROP, Po.1/MIP and WI while no differences were observed for Vesb and IEQ. The sensitivity and specificity for the new indexes were respectively: fsb/Vtsb: 0.65 and 0.58; CROP: 0.70 and 0.63; P0.1/MIP: 0.85 and 0.36; WI: 0.69 and 0.47. CONCLUSION: A statistically significant difference between successful and unsuccessful groups was observed for some but not all new indexes; the diagnostic accuracy of the new indexes were no better than additional parameters.

Adult↗
PubMed1996

[Effect of verapamil on left ventricular hypertrophy induced by isoproterenol].

PURPOSE: We evaluated whether verapamil (VERA) has a protective effect on left ventricular hypertrophy (LVH) induced by Isoproterenol (ISO) in rat. METHODS: Seventy two male adult rats were divided in four groups and treated accordingly during eight days: Control (CON), VERA (10 mg/kg), ISO (0.3 mg/kg) and VERA + ISO. It was measured in 10 animals from each group heart rate, blood pressure, left ventricle dry weight and ratio between left ventricular weight (LVW) and rat weight. Samples were taken from the left ventricle to be examined by light microscopy. RESULTS: LVW of the CON group was 0.145 g, of VERA was 0.144 g, of ISO with 0.201 g, and of VERA + ISO was 0.148 g. The difference between ISO group and others was statistically significant (P < 0.05). The LVW/W ratio also showed similar result. The myocardial pattern induced by ISO was left hypertrophy and collagen content increase. In VERA + ISO group it was found a protective effect to hypertrophy (ISO group 97% vs VERA + ISO 87%; p < 0.001) and increased collagen content. CONCLUSION: VERA prevents the deleterious effects of ISO in the myocardium. Probably this action is due to prevention the myocardial hypertrophy and proliferation of collagen tissue.

Animals↗
PubMed1995

Regulation of apoptosis induced by the retinoid N-(4-hydroxyphenyl) retinamide and effect of deregulated bcl-2.

The cancer chemopreventive retinoid N-(4-hydroxyphenyl)-all-trans retinamide (HPR) was recently shown by us to have antiproliferative and apoptotic effects on human leukemic cell lines, including those unresponsive to all-trans retinoic acid (ATRA). We have now characterized further the process of HPR-induced cell death. We report that inhibitors of RNA transcription and of protein synthesis, activators of protein kinase C (PKC), inhibitors of tyrosine kinases, Zn++, and the antioxidants acetylcysteine, ascorbic acid, alpha-tocopherol, and deferoxamine suppressed HPR-induced apoptosis. HL60 cells induced toward monocytic differentiation by 1,25 dihydroxyvitamin-D3 [1,25(OH)2D3], but not those induced toward the granulocytic differentiation by ATRA, showed reduced responses to HPR. The transport of HPR by cells with different sensitivity to the retinoid, however, was similar, even after treatment with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), which induces unresponsiveness to HPR. The expression of the apoptosis-related genes bcl-2, p53, and c-myc was examined to determine their role in HPR-triggered cell death. The levels of bcl-2 mRNA were markedly diminished by 24 hours of HPR treatment in all cell lines except in the relatively HPR-insensitive line K422. However, probably because of its long half-life, bcl-2 protein levels were either unchanged or only slightly decreased. Downregulation of p53 mRNA was also observed within 24 hours of HPR exposure in NB4 but not K422 cells, but no changes in the amount of p53 protein were found. Suppression of c-myc transcription was observed in all cells except K422. The protective role of bcl-2 on cell death by HPR was investigated in HL60 as well as 697 pre-B leukemia and Jurkat T-acute lymphocytic leukemia (T-ALL) cells constitutively expressing high levels of bcl-2 proteins due to gene transfer manipulation. Compared with control cells, the onset of apoptosis in these cells with deregulated bcl-2 production was delayed by at least 24 hours. These findings establish that cell death by HPR requires RNA transcription and protein synthesis and is regulated by the activation of PKC. Although changes in bcl-2, p53, and c-myc expression are found in cells treated with HPR, the time-course of these events suggests that HPR-triggered apoptosis is not directly controlled by these genes. Finally, while ectopic overexpression of bcl-2 does not protect cells from death by HPR, it markedly delays its onset.(ABSTRACT TRUNCATED AT 400 WORDS)

Anticarcinogenic Agents↗
PubMed1995

Controlled clinical trials with fenretinide in breast cancer, basal cell carcinoma and oral leukoplakia.

We are conducting three randomized studies (breast cancer, basal cell carcinoma, oral leukoplakia) and report our methodological approach and accrual here. The aim of the breast cancer study is prevention of a contralateral primary lesion in women already treated for breast cancer; the aim of the basal cell carcinoma study is prevention of recurrences or new occurrence after surgical resection; and the aim of the oral leukoplakia study is prevention of recurrences and new occurrence after CO2 laser resection. The studies were planned according to a randomized design with an intervention arm vs a no-treatment arm. Patients in the intervention group receive 4-HPR at a dose of 200 mg po. The duration of treatment is five years in the breast cancer study, and one year in the basal cell carcinoma and oral leukoplakia studies. The breast cancer study started in March 1987, closing accrual on July 31, 1993. A total of 2,972 patients entered the study; 2,849 were evaluable (1,422 in the 4-HPR group and 1,427 in the control group). Of 2,849 evaluable patients, 867 completed the first five years, 1,142 are still ongoing, and 840 patients have interrupted the study for various reasons. Follow-up is ongoing. The basal cell carcinoma study started in January 1990. As of January 1994, a total of 786 patients had entered the study; 760 were evaluable (363 in the 4-HPR group and 367 in the control group). Of 760 patients in the study, 568 completed the first year, 62 are ongoing and 130 discontinued for various reasons. The study is ongoing.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticarcinogenic Agents↗
PubMed1995

p53 gene point mutations in relation to p53 nuclear protein accumulation in colorectal cancers.

It is known that structural alterations of the p53 tumour suppressor gene cause malignant transformation and tumour progression in colorectal mucosa. In this study, 38 colorectal cancers were analysed for mutations detected in the p53 gene by single-strand conformational polymorphism and DNA sequence analysis, and the results were compared with p53 protein expression detected by immunohistochemistry. A very strict association (P < 0.0001) was found between genetic alterations and protein accumulation, as detected by the PAb 1801 monoclonal antibody. p53 expression and gene mutations were more frequent in rectal than in colonic cancers. No relation was observed with Dukes' stage, even though most of the mutations were at exon 7 in Dukes' A-B cancers and almost all mutations at exon 8 were observed in Dukes' C-D cancers. DNA ploidy was not generally associated with p53 protein expression or gene mutations. However, 83 per cent of cases with exon 5 and 6 mutations were diploid or near-diploid and 71 per cent of cases with mutations at exons 7 and 8 were aneuploid. Tumours with p53 gene mutations at exon 5 had a higher median [3H]thymidine labelling index (17 per cent) than those with mutations at exons 6, 7, and 8 (11.8 per cent).

Base Sequence↗
PubMed1995

Changes of mitochondrial cytochrome c oxidase and FoF1 ATP synthase subunits in rat cerebral cortex during aging.

The contents of subunits I, II/III, and IV of cytochrome c oxidase and of subunits alpha, beta and gamma of FoF1 ATP synthase in inner mitochondrial membrane proteins purified from cerebral cortex of rat at 2, 6, 12, 18, 24, and 26 months of age were analyzed by western blot. Age-related changes in the content of subunits, either of mitochondrial or nuclear origin, were observed. All the cytochrome c oxidase (COX) subunits examined showed an age-related increase from 2-month-old rats up to 24 months with a decrease at the oldest age (26 months). The same pattern of age-dependent changes was observed for gamma ATP synthase, while the alpha and beta subunits increased progressively up to 26 months.

Aging↗
PubMed1995

Racemose neurocysticercosis after chronic meningitis: effect of medical treatment.

A patient affected by racemous neurocysticercosis, occurring 5 years after the onset of chronic meningitis and followed by sequential MRI studies, is described. After ventriculo-peritoneal shunt, he was successfully treated with Praziquantel and Albendazole. This case may contribute to understand the natural history of the disease and stress the efficacy of medical versus surgical treatment of this lifethreatening disease.

Adult↗
PubMed1995

Protection of testes during radiation treatment by irregular and focused fields of 25 MV x-rays: in vivo evaluation of the absorbed dose.

During therapeutic irradiation of subdiaphragmatic nodal areas, the gonads are exposed to radiation from the primary beam and scatter. Since young patients have a high probability of cure, limiting exposure to the gonads should be pursued. Primary shielding may be supplemented by additional shields in order to reduce this exposure. Testes dose measurements were performed with thermoluminescent dosimetry (TLD) in 37 patients treated with 25 MV x-rays on subdiaphragmatic nodal areas. Each patient was measured 5 times while under treatment. In 27 cases, an additional shield was placed to protect the testes. For 9 cases, comparative measurements were performed on a phantom with and without additional shielding. The median dose received by gonads was respectively 3% with additional shielding (27 cases) and 5.8% without additional shielding (10 cases, p = 0.001 Mann Whitney test). In the 6 patients for whom the measurements were compared, the differences were also statistically significant (p = 0.028 paired Wilcoxon test). This study confirmed the benefit of additional gonadal shielding during subdiaphragmatic radiation treatment with 25 MV x-rays.

Adolescent↗
PubMed1995

Effect of melphalan and hyperthermia on cell cycle progression and cyclin B1 expression in human melanoma cells.

We have investigated the effect of mild hyperthermia (42 degrees C) on the cytotoxic activity of a 1 h melphalan exposure in human melanoma cell lines. Hyperthermia did not affect cell growth of any culture, but it increased, to a different extent, melphalan cytotoxicity in all cell lines, with a reduction in the IC50 of 1.7 to 2.6-fold. Flow cytometric analysis showed that in normal temperature conditions melphalan caused S phase cell accumulation, which was evident only at 24 h in JR8, M14 and 2/21 cell lines and was still persistent at 72 h in 2/60 cells. Moreover, in all cell lines, the delay in S phase was paralleled, or followed, by an accumulation of cells in G2+M, which was transient in JR8 and M14 cells and persisted until 72 h in 2/21 and 2/60 melanoma clones. Hyperthermia caused a stabilization and prolongation of melphalan induced G2+M accumulation in JR8 and M14 cells. Conversely, in 2/21 and 2/60 clones, cell cycle perturbations induced by the drug were similar under normothermic or hyperthermic conditions. Specifically, in JR8, for which the maximum enhancement by hyperthermia on melphalan cytotoxicity was observed, cell accumulation in G2+M was still present 120 h after treatment. The accumulation was accompanied by an inhibition in the G2-M transition, as demonstrated by the significant reduction in the mitotic index of cells exposed to combined treatment compared to controls. Moreover, a bivariate distribution of cells stained for DNA and cyclin B1 showed that, following melphalan and hyperthermia treatment, the fraction of cyclin B1-expressing cells paralleled the fraction of G2+M phase cells, thus indicating that the inability of cells to enter mitosis was not ascribable to a reduction of cyclin B1 expression. On the whole, our results indicate that hyperthermia can stabilize the G2 accumulation induced by melphalan in human melanoma cells. Such a stabilization could contribute to the enhancement of melphalan cytotoxicity by heat, even though a strict correlation was not observed between the magnitude and persistence of the cell cycle perturbations and the extent of melphalan activity.

Cell Cycle↗
PubMed1995

Inhibitory effects of SR 58611A on canine colonic motility: evidence for a role of beta 3-adrenoceptors.

1. In order to clarify whether atypical or beta 3-adrenoceptors can modulate canine colonic motility in vivo, we studied the effects of SR 58611A (a selective agonist for atypical beta-adrenoceptors) alone and after pretreatment with beta-adrenoceptor antagonists on colonic motility in the conscious dog. The gastrocolonic response (postprandial increase in motility) was monitored by means of electrodes and strain-gauge force transducers chronically implanted along the distal colon. In some experiments, heart rate was also measured. The possible role of beta 3-adrenoceptors in mediating the effects of SR 58611A was also tested in vitro in circular muscle strips taken from the canine distal colon. 2. Intravenous infusion of SR 58611A, ritodrine or isoprenaline at doses inducing the same degree of tachycardia inhibited the gastrocolonic response to a different extent, with SR 58611A and ritodrine being more effective than isoprenaline. 3. In a dose-response study, SR 58611A was more potent in inhibiting colonic motility than in inducing tachycardia: the ED35 values for inhibition of colonic motility and induction of tachycardia were 23 and 156 micrograms kg-1, i.v., respectively. 4. The inhibitory effect of SR 58611A 100 micrograms kg-1, i.v., on the gastrocolonic response was reversed by alprenolol (non-selective beta-adrenoceptor antagonist), but resistant to CGP 20712A (beta 1-adrenoceptor antagonist) or ICI 118551 (beta 2-adrenoceptor antagonist). 5. In vitro, SR 58611A concentration-dependently relaxed circular muscle strips, an effect that was competitively antagonized by alprenolol with a pA2 value of 7.1, but resistant to CGP 20712A (100 nM), ICI 118551 (100 nM) or tetrodotoxin (1 microM). 6. The present study provides strong functional evidence for a role of atypical or beta 3-adrenoceptors in the modulation of canine colonic motility both in vivo and in vitro by an inhibitory effect most likely at the smooth muscle level.

Adrenergic beta-Agonists↗