"Atypical" multidrug resistance in human ovarian cancer cell line A2780 selected for resistance to doxorubicin (A2780 DX3).

Human ovarian cancer cells A2780, selected for resistance to doxorubicin (A2780-DX3), are cross-resistant to various other topoisomerase-II-targeted drugs but not to vinblastine. The parental cell line was very sensitive to doxorubicin-, mitoxantrone- or etoposide(VP16)-induced DNA single-strand breaks, under deproteinizing conditions. In contrast, little or no DNA strand breakage was seen in resistant A2780-DX3 cells, even at very high concentrations, indicating a good correlation, with cytotoxicity.

[Multiple heterogeneous cysts of the jaw. A clinical case].

A 23-year-old white man was referred to this Odontostomatologic Service for evaluation of palatal swelling lesion. Oral inspection showed a poor oral conditions and multiple caries. A panoramic radiograph revealed 3 mandibular and 4 maxillary radiolucent lesions.

Induction of DNA double-strand breaks by 8-methoxycaffeine: cell cycle dependence and comparison with topoisomerase II inhibitors.

We have studied the ability of 8-methoxycaffeine (8-MOC)--one of the most effective caffeine derivatives in inducing chromosomal aberrations--to induce DNA double strand breaks (DSB) in purified human T lymphocytes during the cell cycle. Etoposide- or ellipticine-mediated DNA break frequency was used as a parameter of topoisomerase II activity. DNA-DSB induced by either 8-MOC or VP16 or ellipticine rose co-ordinately with the level of DNA topoisomerase II and with the onset of DNA replication.

Sister-chromatid exchanges, chromosomal aberrations and cytotoxicity produced by topoisomerase II-targeted drugs in sensitive (A2780) and resistant (A2780-DX3) human ovarian cancer cells: correlations with the formation of DNA double-strand breaks.

Doxorubicin, ellipticine and etoposide are antineoplastic drugs with topoisomerase II inhibitory activity. The relationship between drug-induced sister-chromatid exchanges (SCEs) or chromosomal aberrations (CAs) and cytotoxicity, or drug-induced DNA double-strand breaks (DSBs) and cytotoxicity, or drug-induced SCEs and DSBs was investigated in human ovarian cancer cells sensitive (A2780) and resistant (A2780-DX3) to topoisomerase II inhibitors. 30-min drug treatments produced SCEs, CAs and DSBs in sensitive cells, doxorubicin being more potent than etoposide at equimolar concentrations.

K-ras and p53 gene mutations in pancreatic cancer: ductal and nonductal tumors progress through different genetic lesions.

We studied K-ras and p53 gene mutations in a panel of 57 primary pancreatic cancers including ductal and nonductal tumors. DNAs were obtained from formalin-fixed, paraffin-embedded material. Target sequences were amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis and sequencing.

Circumvention of atypical multidrug resistance with tumor necrosis factor.

Some "multidrug-resistant" (MDR) cell lines are not associated with a defect in drug accumulation or with the overexpression of P-glycoprotein. These cell lines are defined as "atypical MDR" (at-MDR) and they often express altered or mutated topoisomerase II. We investigated the ability of tumor necrosis factor to reverse at-MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its efficacy in potentiating in vitro topoisomerase II-targeted drugs, and because there is convincing evidence that the synergy is due to an increased number of topoisomerase-associated strand-breaks as well as to an increased level of extractable topoisomerase.

Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients.

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas.

Low doses of scopolamine increase cardiac vagal tone in the acute phase of myocardial infarction.

Background: Reduced cardiac vagal tone in patients with myocardial infarction (MI) is associated with a high risk of sudden death. Muscarinic blocking agents in small doses induce a paradoxical increase in cardiac vagal activity in normal subjects. We tested whether low doses of scopolamine delivered transdermally enhance tonic and reflex cardiac vagal activity in patients in the acute phase of MI.

Determinants of left ventricular function before and after regression of myocardial hypertrophy in hypertension.

Using digitized M-mode echocardiograms, we evaluated the determinants of left ventricular (LV) systolic and diastolic function in 30 hypertensives with LV hypertrophy (LV mass > 230 g and normal LV diastolic diameter), before (LV mass 319 +/- 26 g) and after normalization of LV mass (196 +/- 21 g) by antihypertensive treatment with angiotensin converting enzyme inhibitors. As a control group we selected 50 normal subjects. Using multiple regression analysis we studied the relative role of preload (LV end-diastolic diameter), afterload (end-systolic wall stress), inotropic state (systolic pressure/end-systolic LV diameter ratio), and LV mass on LV systolic (peak shortening rate of LV diameter) and diastolic function (peak lengthening rate of LV diameter).

Properties of Azotobacter vinelandii rhodanese.

Rhodanese (thiosulfate: cyanide sulfurtransferase, E.C. 2.

Diffuse leptomeningeal melanomatosis of the spinal cord: a case report.

A rare case of diffuse leptomeningeal melanosis presenting with symptoms of spinal cord compression due to the presence of anterolateral arachnoid cyst and treated with Spetzler's drainage system is reported. The diagnosis of diffuse melanosis of the leptomeninges is rarely possible during life. In the present case MRI was of great help in the definition of the limits of the pathological process and the presence of the anterior compressing cyst.

Reversal of "atypical"-multidrug resistance by recombinant human tumor necrosis factor in the human ovarian cancer cell line A2780-DX3.

A2780 human ovarian cancer cell line and its multidrug resistant counterpart A2780-DX3 were utilized for this in vitro study. A2780-DX3 is resistant in various degrees to several topoisomerase II inhibitors but sensitive to vinca alkaloids. Simultaneous treatment of the A2780-DX3 line with 1000 U/mL rHuTNF largely reverses resistance to most topoisomerase II inhibitors.

[Preclinical changes in left ventricular function in obesity. An angioscintigraphic study].

Equilibrium pool scintigraphy was performed in 11 obese subjects (BMI 34 +/- 2) and in 14 normal control subjects. Temporal and spatial smoothing of the data was then performed followed by time-activity curve generation using a semiautomatic second derivative edge-detection algorithm. The increase in counts during the first third of diastole divided by the total change in number of counts during diastole was determined as the one-third filling fraction.

Early and multifocal tumors in breast, salivary, harderian and epididymal tissues developed in MMTY-Neu transgenic mice.

Transgenic mice carrying various oncogenes driven by mammary gland specific enhancers develop mammary tumors usually arising in a stochastic way. The only exception is a mouse lineage (TG.NF) carrying an activated rat Neu oncogene driven by the murine mammary tumor virus long terminal repeat (MMTV-LTR) that gave rise to rapid and multifocal mammary tumors interpreted as a result of a single-step neoplastic transformation.

Histopathology, hormone products, and clinicopathological profile of endocrine tumors of the upper small intestine: A study of 44 cases.

Forty-two duodenal and 3 upper jejunum tumors from 44 patients were investigated. All tumors were tested immunohistochemically for gastroenteropancreatic hormones and general endocrine cell markers. Twenty-eight of the 45 tumors (62%) proved to be gastrin cell tumors, with (12 cases) or without (16 cases) associated Zollinger-Ellison syndrome.

[Is hypereosinophilic syndrome a potentially malignant condition?].

The existence of eosinophilic leukemia (EL) has been controversial since it was first described. Recently, some authors have suggested that EL is part of a spectrum of eosinophilic diseases termed hypereosinophilic syndrome (HS). EL diagnosis is very difficult, especially if abnormal chromosome are not present, because HS comprises multiple disease entities of unclear etiology with the common features of prolonged eosinophilia of undetectable cause and organ system dysfunction.

Classification and histogenesis of gastroenteropancreatic endocrine tumours.

A series of 267 gastroenteropancreatic endocrine tumours has been revised from the point of view of histopathologic diagnosis, hormonal profile and clinical behaviour. Results of this investigation, together with revised concepts on the histogenesis of gastroenteropancreatic endocrine growths, allowed to develop detailed classification systems which proved useful for precise tumour diagnosis and for clinicopathologic correlation, with special reference to tumour function, prognosis and therapy. Among 132 pancreatic growths, various types of islet cell tumours (61 cases), with (45 cases) or without (16 cases) hyperfunctional syndrome, were separated from different types of gut-related (38 cases) and 'ectopic' (three cases) tumours, as well as from 25 non-functioning, locally symptomatic tumours, three small cell carcinomas and two mixed endocrine-exocrine tumours.

Premonitory symptoms in migraine without aura: a clinical investigation.

Thirty-three out of 100 patients affected by migraine without aura, reported premonitory symptoms in at least 50% of attacks and were considered to be affected by complete or premonitory common migraine. This group had a greater positive familiarity for migraine, a lower mean age of onset, and a higher average number of trigger factors compared with other patients. These three differences were statistically significant; hence we hypothesized that patients with migraine attacks generally preceded by premonitory symptoms have a stronger constitutional migraine trait with a premature weakening of their antinociceptive adaptation systems to the environment and to stressful events.

[Factors influencing left ventricular function in arterial hypertension].

Using digitized M-mode echograms we evaluated the role of preload, afterload, inotropic state and left ventricular (LV) mass on LV systolic and diastolic function in 2 groups of hypertensive patients: Group 1: 25 subjects (18 men, mean age 48 +/- 6 years) with normal LV mass (less than 230 g); Group 2: 25 subjects (20 men, mean age 50 +/- 8 years) with LV hypertrophy (wall hypertrophy with normal LV diameter). As control group, we evaluated 50 normal subjects, matched for age, sex and body surface area with hypertensives. LV mass was significantly (p less than 0.

Ductal cancers of the pancreas frequently express markers of gastrointestinal epithelial cells.

It has been found by immunohistochemical staining that antigens normally found in gastric and/or intestinal epithelial cells are expressed in most differentiated duct cell carcinomas of the pancreas. Among 88 such tumors, 93% and 92%, respectively, expressed M1 and cathepsin E, markers of gastric surface-foveolar epithelial cells, 51% expressed pepsinogen II, a marker of gastroduodenal mucopeptic cells, 48% expressed CAR-5, a marker of colorectal epithelial cells, and 35% expressed M3SI, a marker of small intestinal goblet cells. Most of the tumors also expressed normal pancreatic duct antigens; 97% expressed DU-PAN-2, and 59% expressed N-terminus gastrin-releasing peptide.

[Papillary cystic tumor of the pancreas].

A case of papillary cystic tumour of the pancreas in a young woman is reported. The review of the literature permits to stress the rarity of this tumour with a good prognosis.

[Description of a system for automatic analysis of ambulatory electrocardiography using a microcomputer].

An automatic ambulatory electrocardiogram analyzer was developed using a self-powered fast reader of FM recorded cassettes and a "general purpose" microcomputer with 640 Kbytes of RAM and 20 Mbytes of mass memory on hard-disk. Original algorithms were developed for analog to digital conversion, data storage on hard-disk, QRS detection and classification and rhythm analysis. Reliability of the system was evaluated, when appropriate, using standard databases.

[Clinical assessment of syncopes].

Syncope is a relatively common clinical problem and causes 1% of hospitalizations. The clinical syndrome is characterized by a sudden reduction of the cerebral flow secondary to a number of conditions that includes benign, self-limited causes and life-threatening arrhythmias. A high percentage of these patients is discharged from hospital without an etiological diagnosis.

[Idiopathic hepatosplenic granulomatosis].

Granulomas in the liver are identified in 3-10% of all liver biopsies. Although granulomas frequently represent a sign of either infectious or non infectious disease, 20% of the hepatic granulomas lack an identifiable etiology. These cases are defined as idiopathic granulomatous hepatitides (IG).