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Biomedical subjects

L Cabral

Publications and source records attributed to L Cabral.

At least 19 recordsLinked to original sources
PubMed1999

Azidothymidine and interferon-alpha induce apoptosis in herpesvirus-associated lymphomas.

Lymphoproliferative diseases that occur in immunocompromised patients are frequently associated with herpesviruses. These patients often fare poorly after treatment with conventional chemotherapy. We reported previously that patients with AIDS-related Burkitt's lymphoma (BL) responded to parenteral azidothymidine (AZT) and IFN-alpha. We found that EBV-positive lymphoma cells derived from these patients cultured with AZT express CD95 and undergo apoptosis. AZT-mediated apoptosis was caspase dependent and occurred despite Fas receptor blockade. In contrast, EBV-negative lymphomas were resistant to AZT-induced apoptosis, as were EBV-positive lymphomas that expressed high levels of bcl-2. Primary effusion lymphoma (PEL) cell lines infected with human herpesvirus type 8 required IFN-alpha to potentiate AZT-induced apoptosis. IFN-alpha did not up-regulate CD95 in BL or PEL but did induce expression of the death receptor ligand, CD95 ligand. AZT-sensitive lymphomas also accumulated significantly higher intracellular AZT monophosphate than did resistant lymphomas. Our data demonstrated distinct apoptotic responses to AZT and IFN-alpha in herpesvirus-associated lymphomas. EBV-positive BL cells that expressed low BCL-2 levels were sensitive to AZT alone; PEL cells required the addition of IFN-alpha to enhance apoptosis, and EBV-negative lymphomas were insensitive to both agents. AZT-sensitive BL cells transfected with BCL-2 became resistant. Susceptibility to antivirus-mediated apoptosis may be exploited to improve the therapy of certain herpesvirus-associated lymphomas.

Apoptosis↗
PubMed1999

Treatment of AIDS-related primary central nervous system lymphoma with zidovudine, ganciclovir, and interleukin 2.

AIDS-related primary central nervous system lymphoma (AIDS PCNSL) is a rapidly fatal disease. Conventional therapeutic modalities offer little and new approaches are needed. Previous work has shown that zidovudine (AZT) in combination with other agents is active in retroviral lymphomas. Epstein-Barr virus (EBV) is detected in tumor tissue and cerebrospinal fluid of AIDS PCNSL patients. In a preliminary in vitro study we found that an Epstein-Barr virus-positive B cell line underwent apoptosis on coculture with AZT. This effect was accentuated by the addition of ganciclovir (GCV). We treated five patients with AIDS PCNSL with a regimen consisting of parenteral zidovudine (1.6 g twice daily), ganciclovir (5 mg/kg twice daily), and interleukin 2 (2 million units twice daily). Four of five had an excellent response. Two patients are alive and free of disease 22 and 13 months later; another responded on two separate occasions, 5 months apart, and the last patient responded with a 70-80% regression of tumor but could not be maintained on therapy owing to myelosuppression. We conclude that parenteral zidovudine, ganciclovir, and interleukin 2 is an active combination for AIDS-related central nervous system lymphoma.

Adolescent↗
PubMed1998

In vitro enhancement of T-cell receptor-targeted lysis after IL-2 treatment of PBL from HIV-seropositive individuals.

Individuals with advanced HIV infection have a greater proportion of T-cells that are activated when compared to uninfected individuals. These activated cells are not able to lyse specific targets. The reason for this dysfunction is not well known. In this study we demonstrate that there are CD8+ T-cells from HIV-seropositive individuals that can be targeted to lyse targets with OKT3 (anti-CD3 antibody) but are unable to lyse targets with WT31 (anti-alphabeta antibody). Treatment of peripheral blood lymphocytes with IL-2 results in an enhancement of WT31-targeted lysis in 9 of 13 individuals evaluated. These findings demonstrate a differential response, in vitro, of CD8+ T-cells to IL-2 treatment. Future work evaluating clinical responses after IL-2 therapy with recovery of targeted lysis in vitro could provide information on screening of individuals for therapeutic intervention.

Adult↗
PubMed1998

Interleukin-2 and leukemia.

Leukemia has been treated with chemotherapy for the past 40 years with only moderate success. A growing body of evidence suggests that by augmenting the immune system more effective results may be obtained. This is highlighted by T cell reinfusions resulting in durable remissions in patients with chronic myelogenous leukemia who have relapsed after an allogeneic transplant. Interleukin-2 is the primary growth factor for T lymphocytes and is a stimulator of natural killer cell activity. It has now been shown that a limited number of otherwise refractory leukemias can be effectively treated with interleukin-2. However, there remains a lack of correlation between the biologic and clinical effects of interleukin-2. The clinical activity of interleukin-2 appears to be greatest in myeloid leukemias. A variety of dose schedules and routes of administration make it difficult to determine if interleukin-2 given to patients in clinical remission is of benefit. Large randomized studies are necessary to explore the role of interleukin-2 in leukemia.

Acute Disease↗
PubMed1998

[Avulsion of the skin of the penis and scrotum].

The authors present a case report of traumatic avulsion of the skin of the penis and scrotum. Surgical treatment was performed in one surgical stage a few hours after the accident. The skin repair of the penis was carried out with a skin graft, while scrotum reconstruction was performed with fasciocutaneous flaps of the inner face of the thighs, with supero-medial pedicle, achieving a good result. The authors justify their choice of procedure, also mentioning the other methods most employed.

Adolescent↗
PubMed1998

[Contributions to the history of burn treatment].

The authors make a brief review of burn treatment in Portugal as well as describing the Burn Unit of the Coimbra University Hospitals. The scientific advances in this area and new perspectives to the future are also mentioned, emphasizing the importance of burn prevention and a complete social reintegration of the burn patient.

Ambulatory Care↗
PubMed1998

[Effect of malting and thermoplastic extrusion on the technologic quality of soybean-derived products].

Seeds of soybean cultivar BR 16 were submitted to malting for 24 and 48 hours and to extrusion originating flakes used as ingredient to make biscuits which were chemically and sensorially evaluated. Macronutrient composition did not show any relevant modification presenting only a small decrease in carbohydrates and increase in the relative lipid composition. Some anti-nutritional factors were affected by the processes. Trypsin inhibitors decreased about 50% after 24 h of malting and disappeared after extrusion. Phytic acid was resistant to the processes while alfa-galactosides presented about 80% of loss as a result of the combination of malting and extrusion.

Female↗
PubMed1996

Retinal pigment epithelial dystrophy in Briard dogs.

The eyes of normal Briard dogs, Briards affected with inherited retinal pigment epithelial dystrophy (RPED) and a range of normal crossbred and beagle dogs were examined and the histopathology of RPED in the Briard was compared with the histopathological features of ageing in the normal canine retina. RPED was characterised by the accumulation of auto-fluorescent lipofuscin-like inclusions in the retinal pigment epithelium (RPE), which initially involved only non-pigmented RPE cells overlying the tapetum but subsequently spread to all pigmented RPE cells. Secondary neuro-retinal degeneration was characterised by a gradual loss of the outer nuclear layer and the subsequent atrophy and degeneration of the inner retina. The loss of primary photoreceptors in the peripheral retina was accompanied by the migration of photoreceptor nuclei and appeared to resemble severe changes due to ageing. Intra-vitreal radiolabelled leucine was used to examine the rate of turnover of the outer segments of the rods in some Briards, but no significant variations were found. The activity of acid phosphatase in RPE was assayed in vitro and showed comparable regional variations in Briard and crossbred dogs. The results suggest that RPED in the Briard is unlikely to be due either to an increased rate of turnover of rod outer segments (and thus an increased phagocytic load) or to a primary insufficiency of lysosomal enzyme.

Acid Phosphatase↗
PubMed1996

Human herpesvirus type 8 DNA sequences in cell-free plasma and mononuclear cells of Kaposi's sarcoma patients.

Human herpesvirus (HHV) type 8 has been detected in both classical and AIDS-related Kaposi's sarcoma, body-cavity lymphomas, and other types of tumors. HHV-8 has also been detected in DNA from peripheral blood mononuclear cells (PBMC) of some Kaposi's sarcoma patients and more readily in B cell fractions derived from panned cell subpopulations. Two patients were followed using several methods; in situ hybridization, solution-based polymerase chain reaction (PCR), and in situ PCR. HHV-8 was intermittently detected in plasma, and detection correlated with detection in PBMC. In situ PCR demonstrated HHV-8 sequences in both peripheral blood B lymphocytes and, to a lesser extent, T lymphocytes. HHV-8 may undergo periods of viremia while at other times it is undetectable and infects circulating B cells and some T cells.

Adult↗
PubMed1995

Treatment of adult T-cell leukemia-lymphoma with a combination of interferon alfa and zidovudine.

BACKGROUND: Infection with the human T-cell lymphotropic virus type I, a retrovirus, can cause a distinctive cancer, adult T-cell leukemia-lymphoma. The median survival of patients with the acute and lymphomatous forms of the disease is short, despite the use of cytotoxic chemotherapy. METHODS: We treated 19 patients with acute or lymphomatous forms of adult T-cell leukemia-lymphoma with oral zidovudine (200 mg five times daily) and interferon alfa (Intron A, 5 to 10 million units subcutaneously each day). Seven of these patients had either relapsed after multiagent cytotoxic chemotherapy or failed to respond to that treatment. RESULTS: Major responses were achieved in 58 percent of the patients (11 of 19), including complete remission in 26 percent (5 of 19). Four patients in whom prior cytotoxic therapy had failed had major responses, two of which were complete remissions. Six patients have survived for more than 12 months, with the longest remission since the discontinuation of treatment lasting more than 59 months. CONCLUSIONS: The combination of zidovudine and interferon alfa has activity against adult T-cell leukemia-lymphoma, even in patients in whom prior cytotoxic therapy has failed. This regimen should be evaluated further for its role in the treatment of adult T-cell leukemia-lymphoma.

Adolescent↗
PubMed1995

Clinical spectrum of HTLV-I in south Florida.

A total of 113 patients with infection due to human T-cell leukemia virus type 1 (HTLV-I) were evaluated at the University of Miami from January 1988 to March 1993. Forty patients were identified with adult T-cell leukemia/lymphoma (ATLL) and 63 with HTLV-I-associated myelopathy (HAM). Three had concomitant ATLL and HAM. Two HAM patients co-infected with human immunodeficiency virus type 1 (HIV-I) developed clonal lymphoproliferative disease during the study period. Patients with ATLL have a poor prognosis; multiple chemotherapy regimens including high-dose cytotoxic agents have been utilized with a small impact on survival. Most of our patients are currently treated with experimental regimens. Rheumatologic or autoimmune illnesses were identified, mostly in HAM patients, and a small number developed immunodeficiencies in the absence of other definable etiologic factors. Most of the patients were immigrants from areas of endemicity in the Caribbean basin, although many Americans were also recognized. HTLV-I/II infection was diagnosed serologically and typed as HTLV-I by polymerase chain reaction (PCR) or a modified Western blot when a DNA sample was not available. In 24 of 40 patients with ATLL, Southern blot hybridization performed on DNA extracted from peripheral blood lymphocytes or tumor tissue demonstrated clonal HTLV-I integration. In South Florida, ATLL and HAM are now seen frequently. Since HTLV-I infection is associated with a 4% lifetime risk of developing ATLL and an additional 0.25% lifetime risk for developing HAM, a large pool of asymptomatically infected individuals must exist here.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Spastic ataxia associated with human T-cell lymphotropic virus type II infection.

Human T-cell lymphotropic virus type one (HTLV-1) is associated with tropical spastic paraparesis or HTLV-I--associated myelopathy. We report 2 women with a spastic ataxic illness similar to HTLV-I--associated myelopathy infected solely with HTLV-II. Identification of HTLV-II infection was made serologically, by polymerase chain reaction, and by viral culture (in 1 woman). One woman, treated with 200 mg of danazol orally, three times daily, had pronounced improvement in ambulation, nocturnal spasticity, and nighttime urinary frequency. It appears that infection with HTLV-II may cause an illness similar to HTLV-I--associated myelopathy, but distinguished by the presence of ataxia.

Antibodies, Monoclonal↗
PubMed1990

Regional distribution of lysosomal enzymes in the canine retinal pigment epithelium.

We have investigated the activities of four lysosomal enzymes in RPE cells isolated from three regions of the canine fundus: the tapetal area, the central pigmented area and the peripheral area. The results obtained with freshly isolated cells showed that the activities of acid phosphatase, B-glucuronidase and N-acetyl-B-glucosaminidase were significantly higher in RPE cells derived from the peripheral region when compared to those from the two central regions. In contrast, the activity of cathepsin D was significantly higher in the tapetal region than in the periphery. The regional distribution of both acid phosphatase and B-glucuronidase observed in fresh RPE cells was progressively lost when these cells were grown in culture. Estimations of photoreceptor density per RPE cell from each of the regions indicated that the number of photoreceptors per RPE cell did not vary significantly with retinal location and suggested that variations in enzyme content were not related to differences in photoreceptor cell distribution.

Animals↗
PubMed1988

A microsystem to assay lysosomal enzyme activities in cultured retinal pigment epithelial cells.

A microsystem to assay the activity of lysosomal enzymes in a small number of cultured RPE cells is described. The activities of acid phosphatase, a-mannosidase, B-glucuronidase and N-acetyl-B-glucosaminidase were estimated in different human RPE cultures of varying passages. Some biochemical characteristics for each of the enzyme assays were studied including the effect of pH, the saturating concentrations of the appropriate substrates and the relationship between the enzyme activity and the number of cells assayed. The method presented is straightforward, avoids complicated tissue fractionation procedures and is able to estimate enzyme activities in as few as 10(4) cells.

Cells, Cultured↗