[Increased prevalence of rectocolonic polyadenomas in patients with acromegaly. Preliminary results in 15 patients].
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Biomedical subjects
Publications and source records attributed to F Dumas.
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This study reports the purification and characterization of a high molecular weight human breast cancer-associated antigen identified by a previously described (1,2) murine monoclonal antibody, BCD-B4. Immunohistochemical analysis indicated that BCD-B4 recognizes an antigen expressed in an altered form on the human breast carcinoma cell line, BT-20, compared to the non-malignant human mammary epithelial cell line, HBL-100. Chemical treatments and enzymatic digestions suggested that the recognized moiety was a protein. The antigenic determinant was resistant to neuraminidase and periodate treatments but was sensitive to trypsin and proteinase K. The antigen was purified by affinity chromatography and its molecular weight, determined by SDS-PAGE analysis under non-reducing conditions, was proven to be 250 Kd. Under reducing conditions, the molecule dissociated into two polypeptides of 125 and 45 Kd, respectively. Both subunits could be isolated from normal HBL-100 and neoplastic BT-20 cellular protein extracts by affinity chromatography. The higher molecular weight subunit showed; however, qualitative and quantitative differences between the two cell lines: it was expressed in greater quantity on BT-20 cells and its molecular weight was 15 Kd higher. Both subunits could also be identified by immunoblots of BT-20 cells.
We have generated three hybridoma-producing monoclonal antibodies (MAs) that show a different spectrum of reactivity to human mammary tissues. Two of these antibodies, 1F10B4 and 1F10G2, recognize a cytoplasmic determinant highly expressed in most of the primary and metastatic breast carcinomas studied, and weakly (or not at all) in normal breast and nonbreast tissues. 3C6F9 detected a surface determinant common to both normal and neoplastic mammary epithelium. Five hundred hybridomas were obtained from the fusion of NS-1 myeloma cells with spleen cells of mice hyperimmunized with the well-characterized human breast carcinoma cell line BT-20. After the initial screenings and clonings, three monoclonal antibodies (1F10B4, 1F10G2, and 3C6F9) showing a restricted range of reactivity were selected for further investigation. These three antibodies recognized a panel of neoplastic mammary cell lines; however, the degree of reactivity could not be correlated to any of the various characteristics of these epithelial cell lines. Moreover, immunofluorescence analysis of acetone-fixed cryostat section showed that 1F10B4 and 1F10G2 recognize the vast majority of the 37 primary and metastatic breast cancers tested, binding strongly to 47% and 67% of them respectively. Only one of the primary carcinomas was not recognized by 1F10B4. On the other hand, these two MAs reacted weakly or not at all with normal breast and nonbreast tissues showing only few focal reactivities with the luminal pole of some ducts of the breast; very weak staining in renal tubular epithelial cells, in few keratinocytes and epithelial cells lining some sebaceous glands in the skin; and a moderate staining in biliary ducts of the liver. All mesenchymal structures including smooth and striated muscle tissues, lymph nodes, and connective tissue were negative. On the other hand, 3C6F9 recognized a more limited number of human mammary tumors and reacted with normal ductal epithelium in the breast and with nonbreast tissues. Because of their wide spectrum of reactivity with breast cancer cells and restricted recognition of normal mammary tissues, their cytoplasmic localization, and their heterogeneous distribution within a single neoplasm, 1F10B4 and 1F10G2 are now being used to characterize antigenic phenotypes of tumor-associated antigens in retrospective studies performed on conventional formalin-fixed, paraffin-embedded human mammary carcinomas.
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Absorption 57Fe Mössbauer spectra have been carried out directly on fresh or lyophylized tissues of liver with either normal iron depot or iron overload. Two types of overloading have been studied: primary iron overload due to an excessive intestinal iron absorption and secondary iron overload (hemosiderosis) produced in beta-thalassemia patients by hypertransfusional therapeutics. The Mössbauer spectra, at room temperature, 77 and 4.2 K, on normal liver samples, are typical for the ferritin-hemosiderin compounds. In the spectra, performed on hemosiderosis liver samples, there appears, in addition to ferritin and hemosiderin, a new iron molecular environment, typical of high spin ferric iron and characterized by a superparamagnetic behaviour which begins at high temperature (above 77 K). This new component does not show up in the primary iron overload cases and seems characteristic of the physiological process which induces the iron overload.
We evaluated the effects of acetazolamide in 4 young patients with Friedreich's ataxia by clinical and quantitative laboratory methods. Dynamic muscle function of the lower extremity was measured during isokinetic knee movements and gait. The acetazolamide trial was terminated at 7 to 11 weeks because of reported side effects or increased ataxia in 3 of the patients. The quantitative evaluations revealed lower dynamic strength values and alterations in the gait movement pattern in all patients. These changes, which were interpreted as deterioration, were partially reversible with cessation of acetazolamide. The advantages of such quantitative evaluations of dynamic muscle function in the evaluation of therapy in Friedreich's ataxia are discussed.
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TDPAC measurements of the 356-81 keV gamma-ray cascade resulting from electron capture decay of 133Ba have been performed at room temperature on BaCl2 (aqueous solution and polycrystalline powder), and on samples where the 133Ba nucleus is bound to bone powder, and also to synthesised hydroxylapatite, all after absorption in vitro. As expected, the angular correlation is not perturbed in the solution. However, in the polycrystalline chloride the time dependence of the anisotropy of the cascade of 133Cs nuclide indicates that the decaying nucleus undergoes electric interactions due to different electric field gradients acting at the site of the nucleus. In 133Ba-bone powder the results show a static quadrupolar interaction differing with the absorption contact time during sample preparation, indicating that depth of 133Ba ion fixation in the bone crystal is dependent on this contact time. These results seem to be confirmed by the TDPAC measurements performed on 133Ba-hydroxylapatite samples where the contact times for absorption of active-ion 133Ba and hydroxylapatite in suspension were very different.
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Emission Mössbauer spectra and Perturbed Angular Correlation measurements have been performed on samples of mineral bone powder labelled with 161Tb3+ or 133Ba2+ ions after either in vitro absorption or uptake by metabolic pathway. The study of these hyperfine spectra, compared with those carried out when 161Tb or 133Ba are situated in either hydroxyde lattice or phosphate one, shows that the uptake modes of rare-and alkaline-earth ions on the bone matrix are different. The rare earth ion seems to be absorbed on the surface bone in an environment of hydroxyl groups similar to the structure of a rare earth hydroxyde. The alkaline earth ion bone uptake appears more complicated and would make according to the following process : at first, surface absorption on the hydroxylapatite in a hydroxyde environment and then cationic exchange with the calcium phosphate groups into bone crystals.
The results of preliminary investigations into the immunolymphscintigraphic (ILS) detection of axillary lymph node metastases in nine breast cancer patients by means of the 3C6F9 monoclonal antibody (MAs) are presented. The IgG2a monoclonal antibody detects a 37 KD antigen, consistently found on the surface of primary and metastatic breast tumors. Each patient received 1 mCi of I-123 (specific activity, 2 mCi per mg of antibody) as a subcutaneous injection between the 2nd and the 3rd finger of both hands, i.e., the healthy side serving as a control for the affected side. Clear images of lymph node metastases were visible 4 to 8 hours after injection of the antibody. Seven of the nine patients studied were positive by scanning and six showed positive lymph node involvement by histopathology (6/7; true positive = 86%). Two patients did not show any iodine uptake in the axilla and were subsequently found to be free of metastases (2/2; true negative = 100%). These data give an overall accuracy of ILS of 89% and demonstrate that 3C6F9 localizes preferentially in affected axillary lymph nodes compared to normal lymph nodes.
OBJECTIVES AND METHODS: HCV cirrhosis is one of the major indications for liver transplantation. HCV recurrence rate is high but long term development to cirrhosis seems to be rare. This study included 28 patients with HCV infection (HCV RNA in blood, histologic lesions highly suggestive or compatible with HCV infection). RESULTS: Twenty-one out of the 28 patients were transplanted for hepatic chronic liver disease associated with HCV infection (reinfection), whereas only 7 out of 94 transplanted patients (7.4%) without pre-transplant HCV infection ("de novo" infection). Patients were followed clinically and histologically for a mean period of 26.8 months (range: 3-56). Of 26 patients with a good histological evaluation, 24 (92.3%) had chronic hepatitis: 7 with mild activity, 17 with moderate activity, 7 of whom had bridging fibrosis. Two patients had unusual features with associated lesions (necrotic hepatitis and chronic rejection in one case, acute hepatitis associated with CMV infection in the other). CONCLUSION: This study confirms the high prevalence of HCV recurrence, as well as the "de novo" infection risk, and suggests caution concerning long term prognosis.