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Biomedical subjects

M Idoate

Publications and source records attributed to M Idoate.

At least 19 recordsLinked to original sources
PubMed1997

Gene transfer and therapy with adenoviral vector in rats with diethylnitrosamine-induced hepatocellular carcinoma.

In rats with diethylnitrosamine (DENA)-induced hepatocellular carcinoma (HCC), we studied in vivo gene transfer efficiency using intraportal injections of recombinant adenovirus carrying the lacZ reporter gene (AdCMVlacZ) and the therapeutic efficacy of adenovirus-mediated transfer of the thymidine kinase gene of the herpes simplex virus (HSV-tk) followed by ganciclovir (GCV) administration. DENA was very effective in inducing HCC but also stimulated nontumor cell replication, as shown by proliferating cell nuclear antigen (PCNA) staining. The study of in vivo gene transfer efficiency in tumor-bearing rats showed that nontumor tissue and small tumor nodules were transduced effectively whereas a poor transduction rate was noted in large tumor nodules. Concerning therapeutic efficacy, three groups of rats with established HCC were studied: group A and B received intraportally recombinant adenovirus carrying HSV-tk (AdCMVtk) or AdCMVlacZ, respectively, and 2 days after GCV was given intraperitoneally for 9 days; group C received only saline. Of the rats from groups B and C, 100% and 93% respectively, exhibited multiple HCC tumor nodules at end of the study. In contrast, a complete regression of tumor was observed in 63% of animals from group A. This group showed significant elevation of serum transaminases and a diffuse hepatotoxic lesion in liver tissue; histological signs of regeneration were observed in surviving animals. Nine out of 19 rats from group A died during the treatment period. We conclude that (i) in the DENA model of HCC, tumoral cells can be destroyed in vivo by the HSV-tk/GCV system despite poor transduction of large tumor nodules, suggesting that toxic metabolites generated by nontumor cells may exert a bystander effect on tumor tissue; (ii) significant hepatoxicity and a high mortality rate occurred in HSV-tk/GCV-treated rats; these side effects appear to be due to the fact that in DENA-treated livers enhanced cell proliferation was present not only in tumor nodules but also in nontumor parenchyma, leading to GCV sensitization of both tissues; (iii) our results have implications concerning the efficacy and potential risks of the HSV-tk/GCV system in the treatment of human HCC.

Adenoviridae↗
PubMed1997

Use of frozen cranial vault bone allografts in the repair of extensive cranial bone defects.

In cranioplasty complexity is proportional to the size of the detect, particularly if greater than 50 cm2. If the patient's own bone flap is not available, allogenic frozen bone graft can be used instead. Between June 1990 and June 1995 twenty cranioplasties with allogenic frozen bone grafts were performed. Age of patients ranged between 23 and 63 years (average 38.4 years). Male/female ratio was 2:1.7. Size of craniectomy ranged between 65 and 150 cm2 (average 83.3 cm2). Follow-up ranged between 10 and 58 months (average 41 months). Donors were tested to rule out transmissible diseases, infections, sepsis and/or cancer. Bone grafts were removed under aseptic conditions, microbiological cultures were taken, wrapped in a gauze soaked with Gentamicin sulphate and Bacitracin, sealed in three sterilised vinyl plastic bags, and stored in a deep freezer for a minimum of 30 days (range 36-93 days, average 67 days), at a temperature of -80 degrees C. Grafts were placed in the defect after a step was carved on its borders to facilitate the contact between host and graft. Vancomycin 1 g. IV/12 hours and Ceftriaxone 1 g. IV/12 hours were administered for five days. Grafts were covered by means of scalp flaps. Only one required a musculocutaneous free flap. None was exposed, extruded or had to be removed. Plain skull X-ray studies showed progressive remodelling of the grafts. Partial resorption was observed in two (2/20, 10%) and loss of thickness in another 3/20 (15%), but with no changes in the contour. Biopsies were taken in 3/20 (15%) cases at a second surgical procedure. Areas of osteoclastic resorptive activity mixed with others of osteoblastic bone apposition, showed replacement with new bone. We conclude that cranial vault frozen allografts are a good alternative to autologous bone when the latter is absent or not present in sufficient amount.

Adult↗
PubMed1997

Dorsal root repair by means of an autologous nerve graft: experimental study in the rat.

Rat dorsal root regeneration was studied after 6th and 7th cervical root surgical removal and replacement with an autologous graft of peripheral nerve harvested from the surval nerve from dorsal root ganglion to dorsal horn. Histological studies showed axonal regeneration within the grafts. When the distal end of the graft was placed inside the posterior horn of the spinal cord by use of a myelotomy, axonal sprouts (revealed by the transganglionic staining method of horseradish peroxidase or HSP) reached the neurones of the posterior horn in a limited fashion.

Animals↗
PubMed1996

Chromosome 17 allelic loss and NF1-GRD mutations do not play a significant role as molecular mechanisms leading to melanoma tumorigenesis.

Allelic loss in human cutaneous melanoma has been detected on chromosomes 1p, 6q, 9p, 10q, and 11q. Chromosome 17 contains important tumor suppressor genes such as p53, NM23, and neurofibromatosis type 1 (NF1), which have been implicated in melanoma tumorigenesis. The role of p53 has already been studied by a number of laboratories, showing contrasting results. In the present study, two restriction fragment length polymorphism (RFLP) probes for the NM23 and NF1 genes, together with five other RFLP and four variable number of tandem repeat chromosome 17 probes, were investigated at the loss of heterozygosity (LOH) level in a Southern blot-based assay. The NF1 gene was also tested for LOH by a polymerase chain reaction (PCR)-based approach in two different experiments, using a dinucleotide repeat polymorphic probe at locus D17S250 (17q11.2-q12), and an Alu probe intragenic to the NF1 gene (17q11.2). A PCR single-strand conformation polymorphism assay was included in the study for mutation detection at the NF1-GTPase-activating protein-related domain (GRD). A total of 68 melanocytic tumors were analyzed. LOH was detected in 9 of 87 informative cases (10%). LEW301 (17p11.2-pcen) presented the highest LOH frequency (22%). NM23 showed LOH in 17% of the informative cases, while NF1 did not show either LOH in the Southern blot- and PCR-based experiments or mutations at the NF1-GRD. These results are in concordance with those of previous smaller studies, but when compared with higher LOH frequencies obtained from other chromosomes, these findings indicate that the LOH values found in our study can most likely be attributed to background effect. Thus, chromosome 17 LOH is likely to play and unimportant role as a genetic event in melanoma tumorigenesis. Nevertheless, NF1 merits further study, since homozygous deletions have been detected at this locus in melanoma cell lines.

Alleles↗
PubMed1995

Multiple pilosebaceous cysts.

We report two patients initially diagnosed as having steatocystoma multiplex (SM). Other cysts showed characteristics of eruptive vellus hair cyst (EVHC). More than 30 and 14 cysts, respectively, were removed with histological hybrid characteristics of SM and EVHC. This suggests that SM and EVCH are two closely related entities, which represent a naevoid malformation in the area where the sebaceous duct and hair follicle meet.

Adult↗
PubMed1994

Granular cell tumor of vulva on episiotomy scar.

The granular cell tumor (GCT) is a rare neoplasm derived from Schwann cells and is considered to be a benign tumor. The vulvar region is one of the common sites for these lesions. Vulvar occurrence of GCT constitutes about 7% of cases. To our knowledge, this is the first case of granular cell tumor of the vulva on an episiotomy scar. GCT should be considered in the differential diagnosis of a benign tumor of the vulva and reactive granular cell lesions.

Adult↗
PubMed1994

p53 expression in cutaneous malignant melanoma: an immunohistochemical study of 87 cases of primary, recurrent, and metastatic melanoma.

Recent studies on the role of the p53 gene in human melanoma have largely been contradictory. To further assess p53 expression in melanoma, we have studied p53 immunoreactivity in 87 cases of primary, recurrent, and metastatic melanoma. Routine immunostaining was performed on paraffin sections with the monoclonal antibody PAb1801 and a streptavidin-biotin method. All specimens were blindly and independently assessed by two observers for number of melanoma cells with granular nuclear staining. Seven melanomas (8%) exhibited from 1 to 50% positive cells and another eight cases (9%) showed p53 immunoreactivity in < 1% of cells. All of the melanomas found to be positive for p53 with one exception (< 1.50 mm) were either thicker than 1.50 mm, recurrent, or metastatic. We conclude that these findings provide little evidence for significant p53 alteration in the initiation and development of melanoma.

Humans↗
PubMed1993

Lack of allelic deletion and point mutation as mechanisms of p53 activation in human malignant melanoma.

To investigate the role of the p53 tumor-suppressor gene in the development of human melanoma, loss of heterozygosity (LOH) of p53 was studied in 46 cases of melanoma by a polymerase-chain-reaction/restriction-fragment-length polymorphism (PCR/RFLP) analysis, and p53 mutations were assessed in 51 cases of melanoma by a polymerase-chain-reaction/single-strand-conformation polymorphism (PCR/SSCP) analysis. Frozen tumors and paraffin samples were used in the study. We were not able to detect any allelic loss in 12BstUI informative cases or any single mutation in exons 5 to 8 of the p53 gene. Our results, together with other findings at the DNA level, suggest that the p53 gene appears not to be commonly involved in the development of melanoma, at least by its most frequent mechanisms of deletion of one allele and/or mutation in the other.

Base Sequence↗
PubMed1993

Mucinous nevus.

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Adolescent↗
PubMed1992

Subcutaneous nodules as the first clinical manifestation of sarcoidosis.

We report the case of a 61-year-old male who presented with a febrile illness accompanied by arthralgia and myalgia. Two months later he developed multiple subcutaneous nodules and enlarged parotid glands. Later two erythematous plaques, clinically compatible with erythema nodosum (EN), were observed. Laboratory investigations revealed abnormal levels of angiotensin converting enzyme and chest radiography showed bilateral hilar enlargement. The biopsy of the cutaneous lesions demonstrated multiple non-caseating granulomas in the subcutaneous tissue without any alterations in the epidermis and the dermis. The cultures for Mycobacteria and fungi were both negative. The clinical picture and histopathological findings were compatible with subcutaneous nodular sarcoidosis. The response to steroid treatment was satisfactory.

Connective Tissue↗
PubMed1992

Pathology of renal transplantation.

Renal transplantation is the most appropriate form of treatment for end-stage renal disease in all age groups. We present the experience of two hospitals in the pathology of kidney allograft. Renal biopsy is the most adequate method for the follow-up of these patients, because it permits the differential diagnosis of acute and chronic rejection, transplant glomerulopathy, recurrent and "de novo" glomerulonephritis and immunosuppression nephrotoxicity, mainly by cyclosporine A. We present the pathology features of all these entities, and study the representativity of the biopsy for diagnosis of rejection. The actuarial survival of the graft is 82% and 71% at 1 and 5 years, respectively.

Biopsy↗
PubMed1990

Subepidermal calcified nodule.

The subepidermal calcified nodule (SNC), included under the idiopathic cutaneous calcifications, is an infrequent cutaneous process. We report a new case localized on the chin of an 18 month old child. We review the concept gathered from previous literature and we post the possible role which the mast cell may play in the genesis of the said deposits.

Calcinosis↗