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Biomedical subjects

J Cardoso

Publications and source records attributed to J Cardoso.

At least 19 recordsLinked to original sources

Expression and genomic profiling of colorectal cancer.

Colorectal cancer still represents a paradigm for the elucidation of the cellular, genetic and molecular mechanisms that underly solid tumor initiation, progression to malignancy, and metastasis to distal organ sites. The relative ease with which pathological specimens can be obtained by either surgery or endoscopy from different stages of tumor progression has facilitated the application of omics technologies to allow the genome-wide analysis both at the RNA (gene expression) and DNA (aneuploidy) levels. Here, we have reviewed the multiplicity of studies appeared to date in the scientific literature on the expression and genomic analysis of colorectal cancer, and attempted an integration of the profiling data generated and made available in the public domain. This approach is likely to pinpoint specific chromosomal loci and the corresponding genes which (i) play rate-limiting roles in colorectal cancer, (ii) represent putative diagnostic and prognostic markers for the accurate prediction of clinical outcome and response to treatment, and (iii) encompass potential therapeutic targets. Moreover, cross-species data mining and integration of the human colorectal cancer profiles with those obtained from mouse models of intestinal tumorigenesis will even more contribute to the elucidation of highly conserved pathways and cellular functions underlying malignancy in the GI tract. Notwithstanding the above promises, tumor heterogeneity, limited cohort sizes, and methodological differences among experimental and bioinformatic approaches still poses main obstacles towards the optimal utilization and integration of omics profiles.

Adenoma↗

Dosimetry at the Portuguese research reactor using thermoluminescence measurements and Monte Carlo calculations.

This work presents an extensive study on Monte Carlo radiation transport simulation and thermoluminescent (TL) dosimetry for characterising mixed radiation fields (neutrons and photons) occurring in nuclear reactors. The feasibility of these methods is investigated for radiation fields at various locations of the Portuguese Research Reactor (RPI). The performance of the approaches developed in this work is compared with dosimetric techniques already existing at RPI. The Monte Carlo MCNP-4C code was used for a detailed modelling of the reactor core, the fast neutron beam and the thermal column of RPI. Simulations using these models allow to reproduce the energy and spatial distributions of the neutron field very well (agreement better than 80%). In the case of the photon field, the agreement improves with decreasing intensity of the component related to fission and activation products. (7)LiF:Mg,Ti, (7)LiF:Mg,Cu,P and Al(2)O(3):Mg,Y TL detectors (TLDs) with low neutron sensitivity are able to determine photon dose and dose profiles with high spatial resolution. On the other hand, (nat)LiF:Mg,Ti TLDs with increased neutron sensitivity show a remarkable loss of sensitivity and a high supralinearity in high-intensity fields hampering their application at nuclear reactors.

Algorithms↗

Photon and fast neutron dosimetry using aluminium oxide thermoluminescence dosemeters.

Al(2)O(3):Mg,Y thermoluminescence (TL) dosemeters were used to measure photon and fast neutron doses in a fast neutron beam recently implemented at the Portuguese Research Reactor, Nuclear and Technological Institute, Portugal. The activation of Al(2)O(3):Mg,Y by fast neutrons provides information about the fast neutron component by measuring the activity of the reaction products and the self-induced TL signal. Additionally, the first TL reading after irradiation determines the photon dose. The elemental composition of the dosemeters was determined by instrumental neutron activation analysis and by particle induced X-ray emission. Results demonstrate that Al(2)O(3):Mg,Y is an adequate material to discriminate photon and fast neutron fields for reactor dosimetry purposes.

Aluminum Oxide↗

Thermoluminescence dosimetry of a thermal neutron field and comparison with Monte Carlo calculations.

The characteristics of thermoluminescence dosemeters (TLDs) regarding the determination of photon and neutron absorbed doses were investigated in a thermal neutron beam. Harshaw TLD-100 (LiF:Mg,Ti) and TLD-700 (7LiF:Mg,Ti) were compared with similar materials from Solid Dosimetric Detector and Method Laboratory (People's Republic of China). Harshaw TLD-700H (7LiF:Mg,Cu,P) and aluminium oxide (Al2O3:Mg,Y) from Hungary were also considered for photon dose measurement. The neutron sensitivity of the investigated materials was measured and found to be consistent with values reported by other authors. A comparison was made between the TL dose measurements and results obtained via conventional methods. An agreement within 20% was obtained, which demonstrates the ability of TLD for measuring neutron and photon doses in a mixed field, using careful calibration procedures and determining the neutron sensitivity for the usage conditions.

Aluminum Oxide↗

Cutaneous infection due to Scedosporium apiospermum in an immunosuppressed patient.

Scedosporium apiospermum, the anamorphic form of Pseudallescheria boydii, is a filamentous fungus with low inherent virulence. Increasing numbers of cases of this infection have been reported probably related to the rising number of immunosuppressed persons. Apart from mycetoma, cutaneous and subcutaneous infection is rarely encountered in clinical practice. We describe a case of cutaneous infection caused by Scedosporium apiospermum in a subject with rheumatoid arthritis and diabetes mellitus who was submitted to long-term therapy with cyclosporin and corticosteroids. Histopathologic examination of a skin biopsy showed a granulomatous infiltrate with hyaline septate hyphae. Culture of two skin biopsies taken at two different observations of the woman, 3 weeks apart, allowed isolation of Scedosporium apiospermum. Therapy with itraconazole, 400 mg/day, for 3 months was effective in curing the infection.

Antifungal Agents↗

Penile paraffinoma.

A 40-year-old Caucasian man, originating from Ukraine, but living for the last year and a half in Portugal, presented to our department with a one year history of an irregular penile mass and phimosis. He reluctantly admitted that 8 years previously he had multiple mineral oil injections in the penis, for the purpose of penile enlargement. A diagnosis of penile paraffinoma was made and surgical excision was performed at the urology department. Paraffinoma results from mineral-oil injections: such practice is very rare in the western world nowadays, however, it still is performed in many Eastern European Countries.

Adult↗

Laser-assisted ICSI: a novel approach to obtain higher oocyte survival and embryo quality rates.

BACKGROUND: Degeneration of oocytes occurs even when maximum care is exercised during ICSI, especially when the oolemma is very fragile and/or the zona pellucida is resistant. In order to be able to minimize the risk of degeneration associated with microinjection this study applied a new method: a microhole on the zona pellucida of the oocyte was drilled by laser beam just prior to ICSI to permit the penetration of the microneedle without any trauma. METHODS: A total of 32 patients (32 cycles) who had one or more previously failed ICSI cycles with a high degeneration rate of oocytes (>20%) were included in the study. Oocytes of the same patients were randomly divided into the study group [laser-assisted ICSI (LA-ICSI)] and the control group [conventional ICSI (C-ICSI)]. The outcomes of the cycles were compared and analysed. RESULTS: After LA-ICSI compared with C-ICSI, survival rates of oocytes were 99.6 and 84% (P < 0.0001), fertilization rates were 76.6 and 68.6% (not significant) and embryo development rates ( vertical line 6 cells on day 3) were 76.5 and 57.3% (P = 0.0024) respectively. CONCLUSIONS: Creating a microhole on the zona pellucida of the oocyte by laser beam prior to ICSI provides a less traumatic penetration of the injection needle into the ooplasm and results in lower degeneration and higher embryo development rates than C-ICSI in patients with fragile oocytes.

Adult↗

Reproducibility of TL measurements in a mixed field of thermal neutrons and photons.

The reproducibility of measurements performed with GR-100 (LiF:Mg,Ti) from the Solid Dosimetric Detector and Method Laboratory (DML) China, GR-107 (7LiF:Mg,Ti, DML), TLD-700H (7LiF:Mg.Cu,P, Harshaw) and Al2O3:Mg,Y (Hungary) in photon and mixed photon-neutron fields was investigated. Mixed-field irradiations were performed in a thermal neutron field generated at a nuclear reactor. GR-100 sensitivity decreased after mixed-field irradiations, while no significant change was found for the other materials. Using GR-100 for the dosimetry of mixed and high-intensity fields requires careful procedures.

Aluminum Oxide↗

Evaluation of HSV-tk gene therapy in a rat model of chemically induced hepatocellular carcinoma by intratumoral and intrahepatic artery routes.

Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene followed by the administration of ganciclovir (GCV) into hepatocellular carcinoma (HCC)-derived cell lines either in vitro or transplanted into nude mice has been shown to provide a potential strategy for HSV-tk-based gene therapy of HCC. We report herein an analysis of the antitumoral efficacy of two recombinant adenoviruses (Ads), Ad.CMVtk and Ad.AFPtk, in a relevant model of multifocal hepatic lesions induced in rats by a potent alkylating chemical carcinogen, diethylnitrosamine. Two routes of administration of the Ad were studied: intratumoral and intrahepatic artery injections. Both recombinant Ads, Ad.CMVtk and Ad.AFPtk, express the HSV-tk gene under the control of the early enhancer/promoter cytomegalovirus and alpha-fetoprotein regulatory gene sequences, respectively. The antitumor response was assessed by magnetic resonance imaging and by autopsy and histological analysis following postmortem. Tumor growth cessation was demonstrated by magnetic resonance imaging in large tumor nodules of size 5-8 mm treated by intratumoral administration of 2x10(9) pfu Ad.CMVtk plus i.p. treatment with GCV. We also show an antitumor efficacy in small tumor nodules of size <3 mm treated with 2x10(9) pfu Ad.CMVtk plus GCV by the intrahepatic artery route, albeit associated with an adverse toxicity. In vivo targeting of the HSV-tk gene to diethylnitrosamine-induced HCC cells with the recombinant Ad.AFPtk suppresses the hepatic toxicity in the nontumoral liver. The lower antitumor response would argue for the use of multiple injections of such adenoviral constructs. These observations may lead to potential approaches for designing gene therapy destined for early treatment of dysplastic nodules or advanced HCC in cirrhosis.

Adenoviridae↗

Bacillary angiomatosis by Bartonella quintana in an HIV-infected patient.

Bacillary angiomatosis and bacillary peliosis are opportunistic infections caused by Bartonella henselae and Bartonella quintana, which occur in patients with late-stage infection. We report a case of bacillary angiomatosis in an HIV-infected patient with skin, bone, and probably liver involvement, The identification of the agent (B quintana ) was done by polymerase chain reaction in the skin specimen. The patient had complete regression of all lesions after a 6-month regimen of oral erythromycin.

AIDS-Related Opportunistic Infections↗

[Utilization of xenogenic liver in human clinics. Tests and perspectives].

Before the 1980s, xenogeneic livers were incorporated for extracorporeal perfusion systems to support failing liver function. Transient improvement in consciousness was seen in some patients developing stage IV encephalopathy. In the 1990s, the growing donor shortage has led to reconsidering the use of xenogeneic livers. In 1992, two baboon livers were successfully transplanted to humans; the survival times were 26 and 70 days. One auxiliary pig liver was unsuccessfully transplanted. Regeneration capacity of the liver in the xenotransplantation context in man was demonstrated using a baboon donor. At the present time physiological, microbiological and immunological problems have not been solved using xenogeneic liver.

Animals↗

["Population and xenograft" investigation. Preliminary results].

The chronic shortage of human organs is the argument for xenotransplantation. In emergencies, acceptability is closely linked to the benefit. Little information is available on attitudes towards xenotransplantation. A poll of the attitudes was carried out, based on a questionnaire with targeted questions and background information. The goal of the study was to have a better understanding of people's attitudes towards xenotransplantation and to know the eventual changes in the answers after having been given information. For 75% of the sample, xenotransplantation would be a future biotechnology. The animal sources that would be considered for xenotransplantation were the pig and monkey. A period of ten years or more is necessary for 69% of the respondents before xenografts are performed routinely; for 19%, five years or less are needed. Human organ donation should be continued, according to 90% of the sample. Roughly, 46.4% support xenotransplantation, though in the case of a life-or-death situation acceptance reaches 65.7%. This level is higher (77%) for relatives or unknown people (71%); 74% of respondents were in favour of using normal animals and a large majority (88%) support research on xenotransplantation. A good level of confidence in medical biotechnology research and practice is suggested by this study, contrary to the results of a European survey on biotechnology.

Adult↗

Predominant role of the Fab fragment in delaying hyperacute rejection in guinea pig-to-rat xenotransplantation.

BACKGROUND: Human intravenous immunoglobulin G delayed xenogeneic hyperacute rejection (HAR) in the guinea pig-to-rat combination. We investigated the respective roles of the Fc and Fab fragments of the IgG molecule in this inhibitory effect. METHODS: By using a guinea pig-to-rat heart transplantation model, the efficiency of IgG, Fab, and Fc in prolonging the grafted heart's survival time (ST) was compared. RESULTS: A dose-dependent increase in the ST was observed with Fab (r=0.74, P < 0.0001), IgG (r=0.57, P < 0.001), and Fc (r=0.51, P < 0.01). The linear regression slopes with Fab and with IgG were, respectively, sevenfold and fourfold steeper than with Fc. The ST was significantly longer than controls (23+/-7 min) after infusion of 2 g/kg IgG (147+/-42 min) or 1 g/kg Fab (176+/-38 min), whereas the highest dose of Fc (1.5 g/kg) did not induce significant prolongation of ST. In terms of equivalent functional doses, 1 g/kg Fab was significantly more potent in prolonging the ST than 1.5 g/kg IgG (87+/-25 min) or 0.5 g/kg Fc (33+/-14 min). Analysis of the rejected hearts evidenced edema, necrosis, and rat C3 deposits characteristic of HAR. CONCLUSION: These results indicated that the delaying action of intravenous immunoglobulin G on HAR in the guinea pig-to-rat combination is mostly mediated through the Fab fragment.

Animals↗

Enhanced in vivo adenovirus-mediated gene transfer to rat hepatocarcinomas by selective administration into the hepatic artery.

Adenovirus-mediated gene therapy of experimental hepatocarcinoma is hindered by low transduction efficacy in vivo. We evaluated the extent of gene expression following various routes of administration of recombinant adenovirus AdCMVlacZ in diethylnitrosamine-induced rat hepatocarcinoma. We first characterized the vascularization of diethylnitrosamine-induced hepatocarcinomas using a computerized tomography scanner approach. The efficacy of gene transfer was then evaluated by three routes of administration: intraportal, selective injection through the hepatic artery and direct injection into the tumor. Diethylnitrosamine-induced hepatocarcinomas had predominantly an arterial blood supply, 67% of the total liver blood supply. Compared with intraportal administration, arterial injection improved gene transfer into tumors whereas that to the non-tumor areas was diminished. In addition, this route of injection allowed the efficient transduction of dysplastic nodules. Diethylnitrosamine-induced hepatocarcinoma in rats is a relevant model for the study of human hepatocarcinoma due to its vascularization. Arterial infusion improved the ratio of transduced tumorous to nontumorous cells and allowed targeting of gene transfer to dysplastic nodules. This will be useful in the design of gene therapy for hepatocarcinoma.

Adenoviridae↗