Gastrointestinal cancer in patients with chronic myeloid leukemia on busulphan treatment.
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Biomedical subjects
Publications and source records attributed to R Mancini.
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Liver fibrosis was induced in rats after administration of dimethylnitrosamine (DMN) intraperitoneally three times a week for 3 weeks. Incomplete septa appeared after 7 days and evidence of nodulation of the parenchyma was observed after 21 days. Both distribution of extracellular matrix components (collagen type I, type III and type IV, laminin, fibronectin, heparan sulphate proteoglycan) and the distribution of desmin as a marker of lipocytes (Ito cells) and of iso-alpha-smooth muscle actin were studied with immunoperoxidase. Changes in the distribution of extracellular matrix components outlined both the formation of septa and the development of nodules with changes in the sinusoidal pattern evoking aspects of capillarization. The number of desmin-positive cells increased in DMN-treated animals, showing a prominent reaction in the fibrous septa. In the normal liver, lipocytes were positive for laminin and negative for actin, but septal and juxta-septal lipocytes were positive for both antigens, suggesting the presence of transitional cells with mixed immunoreactivity. This was confirmed by ultrastructural studies which showed typical intraseptal myofibroblasts and other elements exhibiting the structural features of both myofibroblasts and lipocytes.
The present study is concerned with changes in the number and localization of S-phase cells in the liver of rats exposed to dimethylnitrosamine (DMN). S-phase cells were detected by immunohistochemistry after injection of bromodeoxyuridine (BrdU) and exposure of paraffin sections of liver tissue to the antibody anti-BrdU. With respect to controls, the number of S-phase cells increased four to fivefold in DMN-treated animals in the first week of treatment and remained significantly higher thereafter, in association with the formation of septa. At all times, the labelling index was higher in littoral cells than in hepatocytes. No labelling was observed in biliary cells. This behaviour is different from that reported in other situations, for instance in regeneration after partial hepatectomy, which suggests that besides hepatocytes and littoral cells replacement, an involvement of the latter cell line in the inflammatory reaction, synthesis of extracellular matrix components and formation of septa may account for this particular pattern.
Clinical, haematological, cytogenetic features and therapeutic problems of 51 patients with MDS were examined. Patients were distributed in 5 FAB subgroups: RA 21, SA 7, RAEB 8, RAEB-t 9 and MMCL 6 patients. Leukaemic transformation occurred in 3 RA, 3 RAEB, 7 RAEB-t and 3 MMCL patients. No SA patient suffered from leukaemic transformation. Cytogenetic alterations occurred in 13 of 29 examined patients; 5q- was the most common abnormality. We did not find any relation between chromosomal anomalies and FAB subgroups. Leukaemic transformation, however, was more frequent in patients with cytogenetic aberrations. In some cases it was not easy to determine the precise diagnostic allocation according to FAB subgroups; it is possible, however, to subdivide MDS prognosis into 2 classes. The more satisfactory therapy of leukaemic transformation is often due to low doses of Ara-C; this therapy allowed a better survival and sometimes to obtain CR which in a M6 ANLL patient continued for 24 months.
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The present study is concerned with the early events associated with the development of cirrhosis induced by dimethylnitrosamine (DMN). The antigenic expression of MHC class II components (Ia) and of some intermediate filament proteins (vimentin and desmin) have been studied by immunohistochemistry and the findings correlated with ultrastructural data. Micronodular cirrhosis developed after 3 weeks of treatment with DMN but enhanced expression of Ia antigen on macrophages and on infiltrating lymphocytes was observed after 1 week, before the formation of septa, suggesting that immune-mediated mechanisms are involved in the response to DMN-induced liver injury. The expression of vimentin and of desmin also increased at an early stage and at 3 weeks the septa were outlined by cellular elements showing positivity for both intermediate filament proteins. In keeping with these observations, ultrastructural data showed active division of macrophages in situ, infiltration of the parenchyma by T and B lymphocytes, activation of lipocytes (Ito cells) showing evidence of mitosis, and the presence of transitional elements between lipocytes, myofibroblasts and fibroblasts. This experimental model may be helpful in understanding the relationship between immune-mediated response to liver injury and development of hepatic fibrosis.
The introduction in flow cytometry of the new reagent Streptavidin Duochrome allows the simultaneous three color analysis of biological samples. Streptavidin Duochrome is a phycoerythrin-Texas red fluorochrome complex conjugated to the protein streptavidin. This novel complex exploits the principle fluorescence energy transfer when this reagent is used with FITC, PE and biotin-conjugated monoclonal antibodies; three different emissions of fluorescence are possible simultaneously using an argon laser at 488 nm (FACScan Becton Dickinson). Using Paint-a-gate software which analyses samples and displays the three colors on a screen, antigen distribution on multiple cell populations is obtained. Single, double and triple labeled cells (up to seven combinations) are visualized and quantified quickly and easily. Using a panel of normal donors we have evaluated the following combinations: CD3/CD4/CD8 to visualize T lymphocytes and their subsets; CD3/CD19/CD16 to quantify quickly the T, B, NK populations; CD4/Leu8/Leu18 to analyse the helper subset and CD3/CD8/Leu7. Our purpose is to evaluate the importance of this new kind of analysis to study the heterogeneity of several lymphocytic populations.
Chromosome translocations are consistently present in leukemias and lymphomas and are likely to represent primary events in the development of these neoplasias. A study of conditions that predispose to leukemia could shed some light on the origin of these translocations and therefore help in clarifying their exact role in the process of neoplastic transformation. Based on this assumption, we studied a group of individuals treated with radiochemotherapy for previous lymphoma and who were at increased risk of developing a secondary leukemia. The group comprised 14 Hodgkin's disease patients, 11 non-Hodgkin's lymphoma patients, and 13 controls. The patients were in remission and had been off therapy for at least 6 months. Chromosomes were studied from phytohemagglutinin (PHA)-stimulated peripheral lymphocytes and from bone marrow cells by the direct method and after short-term cultures (72 hours). The latter were also exposed to 5-bromodeoxyuridine (BrdU). Metaphases were scored for chromosome breaks, gaps, and other rearrangements. The percentage of gaps and breaks was significantly higher in patients than in controls. The difference was induced by BrdU and was apparent in bone marrow cells, but not in peripheral lymphocytes. We conclude that individuals exposed to the action of mutagenic agents (radiochemotherapy) have an increased chromosome instability that could be related to their increased risk of developing a secondary leukemia.
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We report on a case of secondary lymphoblastic leukemia L3 in a patient treated with chemo- radiotherapy for a previous Hodgkin's disease. The typical chromosome translocation t(8;14) was found in association with a translocation t(9;19) and a marker chromosome 1, dup(1q). The same marker chromosome had been detected in a few cells of peripheral blood 2 years before the onset of the acute leukemia and may represent a proliferation-associated change, responsible for the initiation of the process of leukemogenesis.
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Atrial septal aneurysm can be detected by subcostal echocardiography as a bulge of the intermediate interatrial septum, ballooning toward the right atrium. We retrospectively revised 5412 echo examinations, consecutively performed in our laboratory, and we found 14 cases of atrial septal aneurysm (0.26%), mean age 36 +/- 15 years, 9 males and 5 females. In 7 patients atrial septal aneurysm was wide, including the whole atrial septum; in 5, only cranial two-thirds of the septum were involved and in 2, it regarded only the intermediate septum. No patients referred to arrhythmias, syncope, embolism, endocarditis or transient ischemic neurologic disorders. Cardiac abnormalities or defects were associated to atrial septal aneurysm in 12/14 patients: they consisted of atrial septal defect, mitral valve prolapse, false ventricular tendons or persistent Chiari network. Atrial left-to-right shunt was detected in all 6 cases with atrial communication. Considering each single associated cardiac abnormality, the prevalence of atrial septal aneurysm was 7% in patients with atrial septal defect, 1.7% in those with mitral valve prolapse, 6.6% in persistent Chiari network and 0.9% in false ventricular tendons. In conclusion, echocardiography is the first-choice technique to detect atrial septal aneurysm and other related cardiac defects.
Hepatic fibrosis has been induced in rats by low doses of dimethylnitrosamine (DMN) and special attention has been paid to early morphological events. DMN (10 microliter/kg body wt., i.p.) was given 3 days a week for 3 weeks to Sprague-Dawley rats. Liver samples were taken on days 7, 14, 21, 28 and 35 and examined by light and electron microscopy. Hemorrhagic necrosis, mainly centrolobular, was evident on day 7, with disruption of the sinusoidal lining, and widening or disappearance of the spaces of Disse invaded by erythrocytes and lymphocytes. Large granular lymphocytes similar to pit cells were also present in close contact with hepatocytes. At day 14, fibrotic septa were associated with cells bearing 'transitional' features between those of lipocytes, myofibroblasts and fibroblasts. Hepatocytes showed foci of increased smooth endoplasmic reticulum, and altered sinusoidal and canalicular membranes. At day 21, all animals showed nodularity of the parenchyma, with evidence of micronodular cirrhosis associated with ascites in two animals. At day 35 (19 days after cessation of treatment) there was little residual inflammation, but well-defined micronodules were still present in all animals. This shows that, in the rat, 3-week treatment with a low dose of DMN produces micronodular cirrhosis following diffuse hemorrhagic necrosis without steatosis. The response of the animals was uniform and reproducible. Lesions of the sinusoidal wall and of membranes of liver cells associated with the inflammatory reaction appeared prominent.
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Twelve patients with dilated cardiomyopathy were studied in order to evaluate whether the favourable effect of Nifedipine on the right heart is due to a direct action of the drug on pulmonary resistances or is related to an improvement of left ventricular function. Echocardiographic examination of left and right heart was performed at basic conditions, after Nifedipine treatment--20 mg sublingually--and after 20 minutes of oxygen breathing (FiO2 75%). This was done in order to verify if oxygen vasodilating action could potentiate the Nifedipine effect. Echocardiographic date were obtained in basic conditions, 10, 20 and 30 minutes after Nifedipine and immediately after oxygen breathing. Ten normal subjects were used for comparison for basic data. Peak Nifedipine activity was observed 10 minutes after administration. At this time inferior vena cava emptying index and systolic pulsation were significantly increased, whereas left and right ventricle isometric contraction time, left and right ventricle ejection time, left and right ventricle isovolumetric relaxation time, end-diastolic left ventricular diameter, inferior vena cava diameters and systolic blood pressure had decreased, thus showing the favourable effect of Nifedipine of both heart sides. Heart rate did not significantly change. Oxygen inhalation induced a significant decrease of right ventricular isovolumetric relaxation and an increase of the inferior vena cava indexes, suggesting an improvement in right heart function, without any change in other parameters. No significant difference was found between data after-oxygen and data obtained 10' after Nifedipine, showing that the Nifedipine effect was not potentiated by oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
A series of 4260 consecutive echocardiographic examinations, performed in 5 Cardiological Centers was examined, identifying 125 intraventricular false tendons (FTs) in 100 cases (55 normals and 45 with heart disease) of whom 31 were female and 69 male, aged 3 to 82 years. An anatomo-morphological study was possible in 9 cases, dead for stroke or heart failure, on autopsy, and in 7, on heart surgery. A phonocardiogram was performed in all normals and in 20 patients. On echocardiography, FTs appeared as an echo-producing string-like structure, straight between the septum and the ventricular free wall, mobile during the cardiac cycle, without systolic thickening and any relation with the atrioventricular valvular apparatus. The prevalence of FTs was 2.3%; it was 3.2% to 5.3% in younger people. FTs were located in the right ventricle (4 cases), left ventricle (95 cases) or in both (1 case). Their site was left apical (45 FTs), right apical (2 FTs), right (3 FTs) and left (20 FTs), upper septum-to-free wall (55 cases). In 1 case hypertrophy of trabeculae of the left ventricle was detected. FTs were single (79 cases), double (19 cases), multiple (2 cases), short (42 cases), long (58 cases), thick (45 cases) and thin (55 cases). They showed a membrane-like motion (thick FTs-45 cases) and a valve-like motion (thin FTs-55 cases). Innocent murmur was detected in 50 of 55 normals and related to thin FTs. Of 16 cases examined anatomically and histologically, FTs were fibrous in their distal portion and fibro-muscular in the proximal one in 12 cases, whereas they were entirely fibrous-muscular in 4 cases. The site and location of FTs detected by echo were confirmed by anatomy in all cases. In 4 cases other 9 FTs, not detected on echocardiography, were found. These data suggest that echocardiography is a useful tool to detect intraventricular FTs and differentiate them from other echo-producing structures. Although a relationship between FTs and heart disease has not been found, their presence could be responsible of innocent murmur in many normal subjects.
Monoclonal antibodies against human fetal haemoglobin (HbF) were obtained by fusion of mouse myeloma cells with spleen lymphocytes from mice immunized against HbF from human umbilical cord blood erythrocytes. Initial antibody screening was by indirect immunofluorescence assays on smeared cord blood and normal adult blood erythrocytes. The specificity of these antibodies was further studied by combined immunoprecipitation assays and direct or inhibition solid-phase enzyme immunoassays. The combined pattern enabled recognition of three types of antigenic determinants: (i) common to both HbF and HbA, by both immunofluorescence and enzyme immunoassays; (ii) common to both HbF and HbA by enzyme immunoassays, present on fixed cord blood erythrocytes and adult thalassaemic erythrocytes by immunofluorescence, but not found on fixed normal adult erythrocytes; and (iii) private HbF by both immunofluorescence and enzyme immunoassays.
Using an automated cytochemical analyzer used for routine differential counts, we have been able to demonstrate acquired myeloperoxidase deficiency in 102 patients at our institution. Clinical and laboratory data on these patients showed a high incidence of diabetes mellitus (25.5%) and thrombotic diseases (24.5%), as well as a strikingly constant hyperfibrinogenemia (mean = 635 mg/100 ml; range = 360-1015 mg/100 ml). In 4 additional acute leukemia patients in complete remission, a close time correlation was noted between acquired MPO deficiency, diffuse intravascular coagulation and relapse. These findings indicate the importance of the relationships between neutrophil granulocytes and blood coagulation, and suggest that similar changes in neutrophil MPO activity may represent an early morphological indicator of subclinical activation of blood coagulation.