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Biomedical subjects

M J Rey

Publications and source records attributed to M J Rey.

36 records · Page 2Linked to original sources

p21WAF1/Cip1 is associated with cyclin D1CCND1 expression and tubular differentiation but is independent of p53 overexpression in human breast carcinoma.

p21WAF1/Cip1 is an inhibitor of cdk/cyclin complexes, and thus regulates the cell cycle. p21 is also related to cell differentiation and is regulated by wild-type p53, although p53-independent regulatory pathways have been proposed. In order to analyse p21 expression as well as its relationship with p53 in human breast cancer, an immunohistochemical analysis was undertaken of 77 breast carcinomas, 16 of them with an in situ component; 30 adjacent normal tissue samples; and five non-neoplastic specimens. Forty-four infiltrating carcinomas (57 per cent) were p21-positive. Expression of p21 was also observed in pre-invasive lesions, whereas normal ducts were negative or focally and weakly positive. p21 expression was associated with high histological grade (II + III) (P = 0.017) and poor tubule formation (P = 0.002), and was significantly less frequent in lobular carcinomas (P = 0.0001). p21 positivity also correlated with increased proliferation, but this seemed to be dependent on the histological grade. Twenty carcinomas (26 per cent) showed p53 overexpression, but this was not associated with p21 negativity, suggesting the existence of p53-independent mechanisms for p21 regulation in vivo. Cyclin D1CCND1 expression was analysed in the same series and an association between p21 and cyclin D1 expression was found, since 23 of 26 cyclin D1-positive carcinomas were p21-positive (P < 0.001 ...). In conclusion, p21 is frequently overexpressed in breast carcinomas and this occurs in the early stages of neoplastic progression. This overexpression seems to be independent of p53 status and might be involved in cyclin D1 modulation.

Blotting, Western↗

Cell cycle regulators and their abnormalities in breast cancer.

One of the main properties of cancer cells is their increased and deregulated proliferative activity. It is now well known that abnormalities in many positive and negative modulators of the cell cycle are frequent in many cancer types, including breast carcinomas. Abnormalities such as defective function of the retinoblastoma gene and cyclin-dependent kinase inhibitors (for example, p16, p21, and p27), as well as upregulation of cyclins, are often seen in breast tumours. These abnormalities are sometimes coincidental, and newly described interplays between them suggest the existence of a complex regulatory web in the cell cycle.

Breast Neoplasms↗

Cyclin D1 and retinoblastoma gene expression in human breast carcinoma: correlation with tumour proliferation and oestrogen receptor status.

Cyclin D1 (CCND1) and retinoblastoma (Rb) genes are cell cycle regulators which are altered in some breast carcinomas. However, the possible cooperation between CCND1 and Rb, as well as the influence and coincidence of their abnormalities in the proliferative capacity of mammary carcinoma cells in vivo, is still unknown. In order to assess both the significance of the CCND1 gene and Rb alterations in breast carcinomas and their relationship with the proliferative capacity of the tumours and other clinico-pathological factors, CCND1 mRNA expression was studied in 46 cases of primary breast carcinomas and matched normal tissue, 45 of which were also studied immunohistochemically, Rb expression was analysed in the same cases by immunohistochemistry, whereas the proliferative activity of the carcinoma was evaluated by flow cytometry. CCND1 mRNA was overexpressed in 19 tumours (41 per cent). Sixteen cases showed diffuse immunohistochemical expression, ten carcinomas had few positive cells, and 19 were absolutely negative. CCND1 mRNA and protein overexpression was associated with oestrogen receptor (ER) expression by the tumour. Interestingly, lack of ER expression was associated with a decreased CCND1 mRNA signal in non-overexpressed tumours. No association was observed between CCND1 mRNA or protein overexpression and tumour proliferation or other clinico-pathological parameters. Loss of Rb expression was observed in 26 per cent of the tumours. This abnormality was significantly associated with increased mean S-phase (P = 0.017) and decreased CCND1 mRNA expression in non-overexpressed tumours, supporting in vivo the postulated regulatory loop between Rb and CCND1 in vitro. We conclude that CCND1 up-regulation is not associated with increased proliferative activity in breast carcinomas, whereas its expression might be regulated in vivo by hormones and Rb. Loss of Rb expression is significantly associated with an increased proliferation of tumour cells, suggesting an important role in the progression of a subset of breast carcinomas, regardless of CCND1 abnormalities.

Blotting, Northern↗

[Xanthogranulomatous cholecystitis simulating gallbladder neoplasm: therapeutic implications].

Xanthogranulomatous cholecystitis (XGC) is an infrequent type of chronic cholecystitis whose histologic features, in some cases, show a macroscopic appearance which may lead to suspicion of a gallbladder neoplasm with the consequent contraindication of the laparoscopic approach. The incidence of XGC was reviewed in a prospective series of 514 cholecystectomies performed in the authors' department from January 1991 to January 1996. Fourteen cases (2.7%) of XGC were identified with a male/female ratio of 1/1.8 and a mean age of 71 +/- 9 years. The most frequent form of presentation observed was hepatic cholic (43%). Echography showed cholelithiasis in 13 patients (93%). In 3 cases (21%), clinical and echographic suspicion of neoplasm was established, two being in the gallbladder, thus contraindicating the laparoscopic approach. A third patient underwent surgery for suspicion of a colon neoplasm. Xanthogranulomatous cholecystitis presents a macroscopic appearance which may be interpreted as a gallbladder neoplasm in up to 25% of the cases thus leading to treatment with laparoscopy.

Aged↗

[Hepatic mesenchymatous hamartoma presenting in an adult patient].

Mesenchymatous hamartoma is a benign liver tumor characteristically found in childhood, particularly during the first two years of life. A case of mesenchymatous hamartoma detected in a 23-year-old female during a study for non specific abdominal disturbances is presented. Imaging techniques showed a large mass in the right hepatic lobe with hypodense areas of cystic appearance. Pathologic study demonstrated the characteristic mixoid mesenchymatous component with areas of cyst formation and rests of liver tissue inside the tumor. Despite its rarity in adults this case demonstrates the need to consider mesenchymatous hamartoma in the differential diagnosis of hepatic masses in adults, particularly when radiologic examination demonstrates cystic components.

Adult↗

Mitral valve rupture following percutaneous mitral commissurotomy: existence of predictive factors.

The purpose of this study was to describe the mechanism and determine predictive factors of mitral valve rupture requiring valve replacement following percutaneous mitral commissurotomy. Of the 350 consecutive patients treated by balloon mitral commissurotomy, the procedure was not completed in 16, and 11 developed acute severe mitral regurgitation requiring valve replacement: seven cases of anterior leaflet rupture, three cases of posterior leaflet rupture and one case of anterior chordal surface. These 27 group I patients were compared to the remaining 323 (group II) in whom the procedure was completed. The 11 excised valves were evaluated by an experienced pathologist. Eight of the 11 patients had an echocardiographic score < 8 (mean score 6.5 +/- 1), no valvular calcification at X-ray and double balloon percutaneous mitral commissurotomy. Microscopy in six patients showed focal fibrous thickening at the site of the rupture but no calcification. One patient developed severe mitral regurgitation due to chordal rupture with an Inoue balloon. The two remaining patients had an echo score of ten and valve calcification on X-ray. Microscopy revealed severe homogeneous chronic rheumatic mitral disease. In one of these two patients, leaflet rupture was related to an 'oversized balloon' (2 x 19 mm + 15 mm). Statistical analysis showed only echo score differences between the two groups (6.9 +/- 1.4 in group I vs 8.2 +/- 1.6 in group II, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Silent maladie de Roger.

A patient with no cardiac murmur was found to have a ventricular septal defect by Doppler echocardiography yet no evidence of pulmonary or right ventricular hypertension. This array of findings is distinctly unusual and appears to be at odds with the clinical teachings concerning small ventricular septal defects.

Adult↗

A new device for specific extracorporeal immunoadsorption of anti-DNA antibodies. In vitro and in vivo results.

Selective removal of anti-DNA antibodies could be an alternative to therapeutic plasma exchange in patients with active systemic lupus erythematosus. The method is based on the immobilization by covalent binding of double-stranded, calibrated, 0.3-kb DNA fragments on a microporous, methylated, polyacrylonitrile membrane. This enables linkage of 60 micrograms of DNA per cm2 of apparent surface area. In vitro, perfusion of 100 ml of plasma maintained at 37 degrees C through 650 cm2 of dsDNA linked to the membrane, at a flow rate of 1.5 ml/min for 60 min, resulted in the removal of 49-89% of anti-DNA IgG without any changes in plasma protein or IgG levels. During a therapeutic plasma exchange, perfusion of the plasma through 1.5 m2 of membrane, at a flow rate of 25 ml/min, initially removed 92% of the anti-dsDNA antibodies entering the adsorbent and 25% at 120 min, indicating a progressive saturation of the binding capacity. Clinical immunoadsorption, at a plasma flow rate of 20-40 ml/min through 2 m2 of membrane, removed more than 50% of anti-dsDNA IgG within 60 min. Microporous membranes are able to irreversibly bind large amounts of antigenic ligands, and enable the selective removal of pathogenetic immunoglobulins or circulating factors.

Antibodies, Antinuclear↗

Intra-hisian 2:1 atrioventricular block secondary to Lyme disease.

We describe a case of Lyme carditis with intra-hisian 2:1 atrioventricular (AV) block documented by electrophysiological study. To our knowledge, only two cases of AV block at the level of the His bundle has been described in the literature. Sinus rhythm was restored after 4 days of i.v. ceftriaxone.

Atrioventricular Node↗

Guidelines for the dosage of neuroleptics. I: Chlorpromazine equivalents of orally administered neuroleptics.

Chlorpromazine (CPZ) equivalents are often used as a relative measure of the antipsychotic potency of neuroleptics. We review the CPZ equivalents of 33 neuroleptics and illustrate why imprecisions or discrepancies will be difficult to eliminate from these values. We nevertheless underline that CPZ equivalents can be clinically useful, since they facilitate the choice of doses of different neuroleptics that should induce comparable antipsychotic effects.

Antipsychotic Agents↗

Guidelines for the dosage of neuroleptics. II: Changing from daily oral to long acting injectable neuroleptics.

When changing from daily oral to long acting injectable neuroleptic therapy, it is essential to choose a dose that will maintain clinical efficacy without increased adverse reactions. Information on pharmacokinetics is needed to achieve this. The authors present guidelines based on this information and observe that previous recommendations sometimes differ substantially from these guidelines. Whether these guidelines will improve the results of long term treatment of psychotic patients remains to be determined.

Administration, Oral↗

Myoepithelial carcinoma arising in a benign myoepithelioma: immunohistochemical, ultrastructural, and flow-cytometrical study.

A case of myoepithelial carcinoma arising in a benign myoepithelioma of the minor salivary gland in a 71-year-old patient is reported. The tumor presented initially on the palate and had been diagnosed as "benign lesion" 40 years before. It recurred 22, 36, and 40 years after initial presentation, and a similar histopathological diagnosis was rendered. One year after the last recurrence, the tumor recurred showing typical changes of malignant transformation, and the diagnosis was malignant myoepithelioma. The light microscopy and ultrastructural features of the initial tumor were typical of plasmocytoid myoepithelioma. There were abundant round cells and rare spindle cells with uniform dispersed filaments, sometimes arranged in parallel streams without evidence of dense bodies. These cells showed micropinocytotic vesicles along the cell membrane with poorly developed intercellular junctions and were surrounded by a basal membrane. The malignant counterpart showed fewer plasmocytoid cells and a rather epithelial pattern with marked nuclear pleomorphism and formation of small, or rarely large, glandular lumina. The immunohistochemical features were similar for the benign and malignant tumors, with positivity for S-100 protein, vimentin, cytokeratins, and CAM 5.2, and were negative for GFAP, muscle-specific actin, CEA, and desmin. Flow cytometry showed a change in the DNA content profile. The benign myoepithelioma had a diploid DNA content with a low S-phase fraction of 3.9% and proliferative index of 9.1%, while the myoepithelial carcinoma had an evident aneuploid DNA stem line and an increased S-phase fraction of 8.3% with a proliferative index of 18.1%.

Aged↗

Value and limitations of cytologic criteria for the diagnosis of hepatocellular carcinoma by fine needle aspiration biopsy.

In order to further evaluate the utility of fine needle aspiration biopsy (FNAB) cytology for the diagnosis of hepatocellular carcinoma (HCC), we analyzed 39 cytologic features in a series of 102 FNABs from HCC and compared them with 28 FNABs from nonneoplastic conditions. Thirteen features were significantly associated with HCC; from them a stepwise logistic regression analysis selected the three most predictive: irregular arrangement, irregular chromatin pattern and uniformly smaller cytoplasm, the last two found only in HCC. Using different specific combinations of significant cytologic features, the highest sensitivity obtained was 84.3%, with 100% specificity. Sixteen HCC cases could not be diagnosed specifically using the criteria defined in this study, probably due to their well-differentiated nature or to sampling error. Although the use of additional techniques, such as cell block preparations, would improve the results in well-differentiated tumors, we recommend basing the early diagnosis of small HCC on a multidisciplinary approach.

Biopsy, Needle↗