Biomedical subjects
Publications and source records attributed to A P Rimondi.
A well circumscribed nodular mass discovered on routine chest ray examination, was excised from the left lung interlobar fissure of a 67 years old woman. Histologically the lesion corresponded to a typical "so called sclerosing hemangioma" according to Liebow and Hubbell's originally description. Because of the uncertain histogenesis we utilized histochemistry and immunohistochemistry to support the hypothesis of an epithelial origin.
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The methylation of the human oestrogen receptor (ER) gene was analysed by restriction enzymes in normal and neoplastic human breast tissues and cell lines. CCGG sequences in regions inside the gene, which are methylated both in normal breast and in tissues that are not the target of the oestrogen, are hypomethylated in 30% of tumours, both ER+ and ER- carcinomas. Moreover, 5' sequences of the gene, which are hypomethylated in normal breast and not in tissues not the target of oestrogen, are methylated to a lower degree in ER+ carcinomas, whereas they are methylated to a greater degree in ER- carcinomas. However, the same region is equally hypomethylated in both ER+ and ER- cancer cell lines. Our results indicate that in breast carcinomas ER DNA methylation is deranged, and in cancer cell lines is different from that observed in primary tumours. Furthermore, the abnormal methylation in the 5' end seems to be related to abnormal expression, namely diffuse hypomethylation in carcinomas with high ER content and hypermethylation in carcinomas without ER. These findings support our previous hypothesis that DNA methylation could be involved in the control of ER gene expression and demonstrate that abnormal ER gene methylation is a typical feature of breast cancers.
A 59-year-old woman on continuous treatment with corticosteroids and immunosuppressive drugs for pemphigus vulgaris of 14 year's duration presented with an enlarging nodular lesion on the right lower eyelid. The neoplasm, diagnosed as basal cell carcinoma, was excised conserving the lid margin, and eyelid reconstruction was done with a rotated cheek flap. Wound healing proceeded without complications in spite of immunosuppressive treatment, and the final cosmetic and functional result was satisfactory.
Demethylation of specific sites or restricted genomic regions has been reported to correlate with gene activation and also with carcinogenesis. As abnormal expression of Estrogen Receptor (ER) could be involved in the genesis or progression of tumors in estrogen target tissues, the methylation of ER gene has been compared in 8 endometrial carcinomas and 29 normal endometria. In order to look for a correlation between methylation and expression, levels of ER RNA were also measured. While the 5' region of ER gene was found to be demethylated in both normal and carcinomatous tissues, there was demethylation of some specific sites in the internal part of the gene only in the carcinomas examined. In addition, in the carcinomatous tissues the levels of ER RNA were low, indicating that an increase of ER gene hypomethylation does not raise, and even may reduce, the ER expression in endometrium. The abnormal undermethylation observed in ER gene appears to be unrelated to general DNA hypomethylation which is frequently present in neoplastic tissues; nor has it been found in ER DNA isolated from breast carcinomas. These data strongly support the hypothesis that such a methylation is specifically related to endometrial transformation and therefore it can be considered an additional marker of this disease.
Restriction enzyme mapping has been used to study the relationship between methylation at the 5' end of the human estrogen receptor gene (ER) and its various levels of expression in estrogen target tissues, like endometrium, placenta and breast. The methylation patterns were compared with that found in white blood cells. A cluster of CpG sites, including the transcription start site, was undermethylated in all examined tissues. In front and downstream of this area, a 1 Kb region was undermethylated in endometrium where the ER gene is highly expressed, methylated to some extent in placenta and breast, which express the gene to a low degree, and greatly methylated in white blood cells which are thought not to express this gene. These data provide evidence that in the 5' end of the human ER DNA, CpG methylation is tissue-specific, and related to the level of the ER gene expression.
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The sclerosant effect of injected tetradecyl sulfate of sodium (STS) and hydroxy polyethoxy dodecan (HPD) was studied in the rat femoral vein. Intravenous (i.v.) and intravenous plus perivenous (i.v. + p.v.) injections of both sclerosants and physiologic saline were compared as to vein lumen occlusion, fibrosis, phlogosis, and damage to the artery and surrounding nervous and muscular tissues. The study was carried out in 30 rats treated by STS, in 30 treated by HPD, and 15 animals were injected with saline. The neurovascular bundle and adjacent muscle were removed at 48 h, 7 and 30 days and examined histologically. I.v. injections of STS produced a solid occlusion of the vein in a significant number of cases, after 30 days (P less than 0.01). A statistically significant number of solid occlusions of the femoral vein resulted after i.v. + p.v. injection of STS and HPD, at 48 h, 7 and 30 days (P less than 0.05; P less than 0.01). There was no significant difference between STS and HPD after i.v. + p.v. injection. After i.v. + p.v. we recorded a marked inflammation of muscle with signs of focal necrosis, at 48 h and 7 days. Our study indicated that i.v. + p.v. injection of STS and HPD provided a high degree of efficacy as regards vein occlusion. On the other hand, i.v. + p.v. injection induced a severe inflammation and necrosis of the tissues surrounding the sclerosed vein. Extrapolating our results to the endoscopic sclerotherapy for esophageal variceal bleeding, we conclude that paravariceal injection of sclerosants is a dangerous procedure, even though efficacious to reduce variceal hemorrhage, owing to the high risk of iatrogenic ulcers and esophageal perforation caused by muscular and mucosal necrosis.
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The methylation pattern of the human HLA-DR alpha gene was analyzed in normal breast tissues, breast primary tumors and lymphonodal metastases isolated from patients carrying breast carcinomas. In breast adenomas and also in normal tissues (including breast, muscle, brain, sperm and T- and B-lymphocytes), the HLA-DR alpha gene is hypermethylated at the CCGG and GCGC sites. In all tissues studied, the only constantly unmethylated region is located in the 5' portion of the gene, near the promoter sequence. Further, the results indicate that the HLA-DR alpha gene is hypomethylated in carcinomas and in the relative metastatic lymph nodes. It is suggested that hypomethylation of the human HLA-DR alpha gene could be proposed as a molecular marker of malignant breast tumors.
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The authors investigated nine factors which can affect the depth of incisions performed during refractive keratotomy: (1) vertical vs oblique-cutting edge of the knife blade, (2) direction of cutting, (3) cutting velocity, (4) American vs Russian technique, (5) intraocular pressure (IOP), (6) initial vs final incisions, (7) sharpness of knife blade, (8) single vs double footplate, and (9) square vs double-edged blade. These variables were examined independently, performing at least 40 incisions for each experimental parameter studied. The depth of the resulting incisions was measured histologically using the micrometer eyepiece. The average and the standard deviation were calculated. The paired Student's t-test was used to establish significant differences between the two conditions investigated for each parameter. Factors that were demonstrated to increase significantly the depth of the incisions included: the vertical-cutting edge, the triple-edged diamond knife, the sharpness of the knife, and the single foot knife. High velocity in performing the incisions and, to a lesser extent, low IOP were the main factors that induced irregularity in depth.