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Biomedical subjects

M A Idoate

Publications and source records attributed to M A Idoate.

At least 19 recordsLinked to original sources

PTEN protein expression correlates with PTEN gene molecular changes but not with VEGF expression in astrocytomas.

PTEN gene (10q23) is a relevant tumor suppressor gene whose protein is a phosphatase involved in the control of angiogenesis of some tumors including astrocytomas. There are no studies correlating molecular changes of PTEN and the immunohistochemical expression of its protein (pPTEN) with the expression of vascular endothelial growth factor (VEGF) in astrocytomas. Fifty-six surgically resected brain gliomas, 10 grade 2, 16 grade 3, and 30 grade 4, were studied by a combined approach, consisting of (1) PCR analysis using four microsatellite markers against the PTEN gene region (10q23), (2) the FISH technique to test chromosome 10 using a pericentromeric probe, and (3) immunohistochemical evaluation of pPTEN and VEGF. Loss of heterozygosity (LOH) of PTEN was observed in 10% of fibrillary grade 2 astrocytomas and all gemistocytic ones. In high-grade tumors, LOH was more frequent in grade 4 than in grade 3 (> or =2 loci deleted, 83% and 56%, respectively). Monosomy for chromosome 10 was observed especially in high-grade tumors (6% of grade 3 and 50% of grade 4) and in 20% of grade 2 tumors, corresponding to gemistocytic astrocytomas. Results with both antibodies against PTEN were concordant: loss of cytoplasmic immunoreactivity was frequently observed according to homogeneous or heterogeneous patterns in 70% and 50% of grades 4 and 3, respectively, but not in grade 2. Immunonegativity of pPTEN was associated with PTEN gene deletion (> or =2 loci deleted) (P = 0.04) but not with monosomy. Cytoplasmic immunoreactivity against VEGF was observed in high-grade and in gemistocytic astrocytomas, but not in conventional grade 2 tumors. Tumor expression of pPTEN was not associated with immunoreactivity against VEGF when the same areas were considered. In conclusion, loss of PTEN expression is frequent in high-grade astrocytomas, but not in grade 2 tumors, and correlates with PTEN deletion and loss of chromosome 10. PTEN immunoreactivity does not correlate with VEGF expression in astrocytomas when similar areas are considered.

Astrocytoma↗

Cutaneous zosteriform squamous cell carcinoma metastasis arising in an immunocompetent patient.

Cutaneous metastases from internal malignancies or primary skin cancers are uncommon, and a zosteriform pattern is very rare. Histologically, these cutaneous metastases usually appear as malignant epithelial cells located throughout the dermis or subcutaneous fat and without connection to the overlying epidermis. The presence of melanocytes in such lesions is atypical. Moreover, although zosteriform cutaneous metastases of cutaneous squamous cell carcinoma have previously been described in immunosuppressed patients, they have not been reported in immunocompetent patients. We report an unusual case of a woman with cutaneous hyperchromic zosteriform metastases, clinically mimicking a metastatic melanoma but appearing histologically as epidermotropic and pigmented metastases of a cutaneous squamous cell carcinoma.

Aged↗

The neuropathology of intestinal failure and small bowel transplantation.

The aim of this study was to elucidate the neuropathological substrate of intestinal failure before and after small bowel transplantation (SBT). Retrospective analysis of complete autopsy or brain biopsy specimens of 17 patients with intestinal failure (12 children and 5 adults) were studied. Patients were divided into two groups. Group I (transplanted group; n = 13) included those patients who underwent intestinal transplantation under tacrolimus and steroids immunosuppressive therapy. Group II (control group) included 4 children with intestinal failure who were candidates for SBT and died while awaiting an intestinal allograft. Central nervous system (CNS) abnormalities were seen in 92% of the SBT recipients and in 100% of SBT candidates. The neuropathological lesions of SBT recipients included: (a) vascular lesions: global brain ischemia, infarcts, intracranial hemorrhage and edema (7 children/2 adults; 69%); (b) cerebral atrophy (6 children; 46%); (c) Alzheimer type II gliosis (5 children/4 adults; 69%); (d) infection (3 patients; 23%) due to cytomegalovirus (1 child), Aspergillus fumigatus (1 adult) and progressive multifocal leukoencephalopathy (PML)-like (1 adult); (e) Epstein-Barr virus-related cerebral post-transplant lymphoproliferative disorder (2 children; 15%); and (f) central pontine and extrapontine myelinolysis (1 child; 7.5%). The neuropathological lesions of SBT candidates were Alzheimer type II astrocytosis (4 patients), vascular changes (4 patients), brain atrophy (4 patients) and cerebral candidiasis (1 patient). CNS vascular, metabolic and infectious pathology are significant causes of morbidity and mortality in patients suffering intestinal failure, both before and after SBT. Brain atrophy was a frequent finding and may be related to nutritional and developmental inadequacy of long-term total parenteral nutrition.

Adult↗

Carbonyl reductase and NADPH cytochrome P450 reductase activities in human tumoral versus normal tissues.

The use of bioreductive agents in enzyme-directed bioreductive therapy has been proposed to take advantage not only of hypoxia in tumours, but also of the presence of reductases that metabolise such compounds. In this study, we studied the activities of NADPH cytochrome P450 reductase (P450R) and carbonyl reductase (CR) in 17 human lung tumours and 18 human breast tumours, together with the corresponding normal tissues. For lung cancer but not for breast cancer there was a significant difference in the CR activity between normal and tumour tissue. CR activity was increased with respect to the normal tissue between 2-fold and 40-fold indicating heterogeneity in tumour samples. No relationship was found between CR activity and the histological type, tumoral grade or TNM stage of the tumours. Although some variation in P450R activity in tumoral versus normal tissues was found in the majority of the samples studied, no significant differences could be demonstrated.

Alcohol Oxidoreductases↗

Disseminated epidermolytic acanthoma probably related to trauma.

Epidermolytic acanthoma is a rare benign tumour, which may occur in both isolated and disseminated forms. Only seven cases of disseminated epidermolytic acanthoma (DEA) have been described. This entity should be distinguished from other hereditary or acquired conditions which involve epidermolytic hyperkeratosis and other benign acanthomas. On the basis of the clinical history and the histological findings, we diagnosed a case of DEA which was probably secondary to repeated trauma.

Adult↗

Molecular features in a biphenotypic small cell sarcoma with neuroectodermal and muscle differentiation.

We report a case of a 13-year-old girl with soft tissue sarcoma of the hand, which showed muscle and neuroectodermal immunophenotypes. Molecular studies were performed on RNA collected from fine-needle aspiration (FNA) cytology and peripheral blood samples by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern blot analysis. This biphenotypic tumor showed simultaneous expression of EWS-FLI1 and PAX3-FKHR transcripts, specific of Ewing family tumors and alveolar rhabdomyosarcoma, respectively. Although childhood sarcomas with simultaneous muscle and neural differentiation have been described to have EWS-FLI1 transcripts, there are no reports of tumors with both transcripts. Cytological specimens are a good source of RNA for molecular studies.

Adolescent↗

DT-diaphorase and cytochrome B5 reductase in human lung and breast tumours.

The level of expression of enzymes that can activate or detoxify bioreductive agents within tumours has emerged as an important feature in the development of these anti-tumour compounds. The levels of two such reductase enzymes have been determined in 19 human non-small-cell lung tumours and 20 human breast tumours, together with the corresponding normal tissue. DT-diaphorase (DTD) enzyme levels (both expression and activity) were determined in these samples. Cytochrome b5 reductase (Cytb5R) activity was also assessed. With the exception of six patients, the levels of DTD activity were below 45 nmol min(-1) mg(-1) in the normal tissues assayed. DTD tumour activity was extremely variable, distinguishing two different groups of patients, one with DTD activity above 79 nmol min(-1) mg(-1) and the other with levels that were in the same range as found for the normal tissues. In 53% of the lung tumour samples, DTD activity was increased with respect to the normal tissue by a factor of 2.4-90.3 (range 79-965 nmol min[-1] mg[-1]). In 70% of the breast tumour samples, DTD activity was over 80 nmol min(-1) mg(-1) (range 83-267 nmol min[-1] mg[-1]). DTD expression measured by Western blot correlated well with the enzyme activity measured in both tumour and normal tissues. The levels of the other reductase enzyme, Cytb5R, were not as variable as those for DTD, being in the same range in both tumour and normal tissue or slightly higher in the normal tissues. The heterogeneous nature of DTD activity and expression reinforces the need to measure enzyme levels in individual patients before therapy with DTD-activated bioreductive drugs.

Aged↗

Transfusion-associated acute graft-versus-host disease in a heart transplant recipient.

We report a heart transplant recipient who developed graft-versus-host disease (GVHD) following blood transfusion. We consider that heart transplant recipients should be included in the category of immunosuppressed patients who may develop this disease after being treated with blood products. We also consider that, at the present time, irradiation of blood products is the only useful method of avoiding development of GVHD in these patients.

Female↗

Anion exchanger immunoreactivity in human salivary glands in health and Sjögren's syndrome.

Salivary gland ducts play a relevant role in saliva secretion through transport processes. Na(+)-independent chloride-bicarbonate anion exchangers (AE) may be involved in these processes by generating ion fluxes into the salivary secretion. In Sjögren's syndrome, a disorder with gland dysfunction, there might be an impaired expression of AE proteins. Here we study AE immunoreactivities in human salivary glands, both in health and in Sjögren's syndrome. Immunohistochemistry was carried out on salivary glands from normal subjects and patients with Sjögren's syndrome, using two monoclonal antibodies against AE1 and AE2. Normal salivary glands showed AE2 immunoreactivity, which was restricted to the epithelium of the ducts, with no staining at the acini. A strong positivity was seen in the basolateral portion of the striated ducts, while interlobular duct cells showed a discrete positivity at their apical pole. In salivary glands from most of the patients with Sjögren's syndrome, AE2 immunoreactivity was absent in the ducts as well as in the acini. In both normal and diseased salivary glands, AE1 immunoreactivity was only located at the erythrocyte membrane. The recently reported AE0 was discarded because no AE0 message was found in salivary glands by reverse transcription polymerase chain reaction. In conclusion, AE2 immunoreactivity is observed in the ducts of normal salivary glands, particularly in the striated ducts. AE2 immunoreactivity is virtually absent in salivary glands from patients with Sjögren's syndrome, which may reflect either a loss of AE2 after inflammatory atrophy, or a primary defect occurring in the disease.

Adult↗

Generalized skin reaction following tinea pedis (dermatophytids).

An 11-year-old boy presented with inflamed tinea pedis followed by a generalized id type skin eruption, with disappearance of the rash after treatment of the mycotic foot lesions. The pathogenesis of this process is not precisely known. Fungal infection was not detected from the generalized skin lesions. Various clinical forms of dermatophytid reaction are discussed.

Child↗