Acrylamide: Dermal Exposure Produces Genetic Damage in Male Mouse Germ Cells

Acrylamide is used extensively in sewage and wastewater treatmentplants, in the paper and pulp industry, in treatment of potablewater, and in research laboratories for chromatography, electrophoresis,and electron microscopy. Dermal contact is a major route ofhuman exposure. It has been shown that acrylamide is highlyeffective in breaking chromosomes of germ cells of male miceand rats when administered intraperitoneally or orally, resultingboth in the early death of conceptuses and in the transmissionof reciprocal translocations to live-born progeny. It is nowreported that acrylamide is absorbed through the skin of malemice, reaches the germ cells, and induces chromosomal damage.The magnitude of genetic damage appears to be proportional tothe dose administered topically.     

Alterations in norepinephrine content and beta adrenoceptor regulation in myocardium bordering aneurysm in human heart: their possible role in the genesis of ventricular tachycardia

On the assumption that alterations in the adrenergic system may play a role in generating ventricular tachycardia in patients with myocardial post-infarction apical aneurysm, we evaluated norepinephrine concentration, number and affinity of both beta 1 and beta 2 adrenoceptors in perianeurysmatic tissue in twelve patients operated upon for congestive heart failure and recurrent sustained ventricular tachycardia. Concentration of norepinephrine in perianeurysmatic tissue was 0.1 +/- 0.05 micrograms g-1 tissue (n = 8), this value being much lower than that found in papillary muscle (n = 10) from patients with mitral valve stenosis (0.8 +/- 0.02 micrograms g-1 tissue) (P less than 0.01). The total number of beta adrenoceptors (71.4 +/- 7.8 v. 48.0 +/- 5.1 fmol mg-1 protein; P less than 0.01) and the percentage of beta 1 subtype were found to be higher in perianeurysmatic tissue (approximately 90%) than in papillary muscle (approximately 68%). Out of twelve patients with aneurysm, beta 2 adrenoceptors had considerably decreased in three patients and were absent in the remaining nine. Decrease in the neuronally released norepinephrine associated with contrasting behaviours of beta 1 and beta 2 adrenoceptors suggests the presence of a profound alteration in the sympathetic innervation of the perianeurysmatic myocardial tissue that may contribute to the genesis of sustained ventricular tachycardia in patients with postinfarction apical aneurysm.     

Supraventricular Arrhythmias in Children and Young Adults with Implantable Cardioverter Defibrillators

INTRODUCTION: Rapidly conducted supraventricular tachycardias (SVTs) can lead to inappropriate device therapy in implantable cardioverter defibrillator (ICD) patients. We sought to determine the incidence of SVTs and the occurrence of inappropriate ICD therapy due to SVT in a pediatric and young adult population. METHODS AND RESULTS: We undertook a retrospective review of clinical course, Holter monitoring, and ICD interrogations of patients receiving ICD follow-up at our institution between March 1992 and December 1999. Of 81 new ICD implantations, 54 eligible patients (median age 16.5 years, range 1 to 48) were identified. Implantation indications included syncope and/or spontaneous/inducible ventricular arrhythmia with congenital heart disease (30), long QT syndrome (9), structurally normal heart (ventricular tachycardia/ventricular fibrillation [VT/VF]) (7), and cardiomyopathies (7). Sixteen patients (30%) received a dual-chamber ICD. SVT was recognized in 16 patients, with 12 of 16 having inducible or spontaneous atrial tachycardias. Eighteen patients (33%) received > or =1 appropriate shock(s) for VT/VF; 8 patients (15%) received inappropriate therapy for SVT. Therapies were altered after an inappropriate shock by increasing the detection time or rate and/or increasing beta-blocker dosage. No single-chamber ICD was initially programmed with detection enhancements, such as sudden onset, rate stability, or QRS discriminators. Only one dual-chamber defibrillator was programmed with an atrial discrimination algorithm. Appropriate ICD therapy was not withheld due to detection parameters or SVT discrimination programming. CONCLUSION: SVT in children and young adults with ICDs is common. Inappropriate shocks due to SVT can be curtailed even without dual-chamber devices or specific SVT discrimination algorithms.     

Beta-2-microglobulin and Helicobacter pylori infection in uraemic dialysed patients

Chronic gastritis in patients with chronic renal failure may have different causes and mechanisms. Recent observations suggest that severe gastritis often found in uraemic patients might be related to Helicobacter pylori (HP) infection. In chronic gastritis HP has been found in the mucus and on the epithelial cell surface of gastric foveolas. Significant infiltration of the subepithelial gastric layer by polymorphonuclear leucocytes has been described. Moreover, beta-2-microglobulin deposits have been found by immunohistochemical methods in the subepithelial layer of gastric mucosa of uraemic dialysed patients with active chronic gastritis and HP infection. Similar findings have also been demonstrated in gastric biopsies from patients with HP positive active chronic gastritis and normal renal function. Since HP infection is associated with significant leucocyte infiltration, it is hypothesized that the inflammatory process causes the release of beta-2-M from the surface of the leucocytes and its subsequent deposition at gastric level.     

THE SPECTRUM OF 67-kD LAMININ RECEPTOR EXPRESSION IN BREAST CARCINOMA PROGRESSION

Laminin is a glycoprotein of the basement membrane (BM), involved in a variety of normal and pathological cellular events including tumour invasion and metastasis. Cells bind laminin through different types of receptor. The 67-kD laminin receptor (67LR) is a cell-surface protein which binds laminin with high affinity. 67LR expression has been shown to increase in neoplastic cells, compared with normal tissues, and 67LR seems to play an important role during the first steps of neoplastic progression. In this study, 67LR expression was analysed during the morphological phases of breast cancer progression from normal tissue to invasive carcinoma. A total of 506 formalin-fixed, paraffin-embedded normal breast structures and lesions were stained by immunohistochemistry using the MLuC5 monoclonal antibody, which is specific for 67LR. The results show that in normal breast and in any kind of breast lesion, myoepithelial and endothelial cells express 67LR. While 67LR is not seen in the epithelium of normal breast, cysts, adenosis, and benign tumours, it is expressed in the epithelial cells of several hyperplasias and carcinomas in situ, both ductal and lobular, as well as in all invasive carcinomas. The 67LR-positive cell subpopulation expands from hyperplastic lesions to invasive carcinoma, suggesting that 67LR could be related to the induction and progression of breast cancer. © 1997 John Wiley & Sons, Ltd.     

BRONCHIOLOALVEOLAR LUNG CARCINOMAS: K-ras MUTATIONS ARE CONSTANT EVENTS IN THE MUCINOUS SUBTYPE

Bronchioloalveolar carcinoma (BAC) is a form of peripheral lung adenocarcinoma growing as a single layer of malignant cells along the walls of terminal airways. The existence of BAC as a separate clinico-pathological entity has been a matter of controversy, mainly because its histogenesis is uncertain and it is not easily distinguishable from conventional lung adenocarcinoma (CLA). Three subtypes of BAC have been described using histological and cytological criteria: mucinous, non-mucinous, and sclerosing. The clinical behaviour of BAC appears to be dependent on the histological subtype. The different morphological patterns and clinical outcome of the subtypes of BAC suggest that their biological behaviour may be different from one another and from CLA. This study has investigated 58 BACs (10 mucinous, 40 non-mucinous, and 8 sclerosing) and 50 control CLAs for mutations at codon 12 of the K- ras oncogene. Twenty-one (36 per cent) BACs and 13 (26 per cent) CLAs showed K- ras mutations. A clear association ( P <0·0001) between K- ras mutations and the mucinous type of BAC was observed: all 10 mucinous tumours examined were scored positive for mutations in the K- ras gene, while only 9 (23 per cent) of the 40 non-mucinous and 2 (25 per cent) of the 8 sclerosing BACs were found to be positive. The frequency of ras mutations in non-mucinous BAC, sclerosing BAC, and CLA was not statistically different. Our data indicate that BACs are a heterogeneous group of lung tumours and that the mucinous form might represent a biological entity separate from both the other two BAC types and CLA.     

The proteins in unheated culture filtrates of human tubercle bacilli; fractionation and determination of physical-chemical properties

Concentrated culture filtrates of two strains of human tubercle bacilli, a virulent and a slightly virulent one, have been fractionated to give fourteen fractions in each case. Chemical determinations and sedimentation velocity measurements have been carried out on those fractions for which significant results could be obtained. The evidence is that two distinct proteins are present, in addition to a polysaccharide and nucleic acid. The physical measurements have not demonstrated the presence of any other proteins. One of the proteins has been isolated in pure form, and found to have a molecular weight of 44,000 +/- 5,000, based on measurements of partial specific volume, sedimentation velocity, and diffusion rate. This protein is believed to be the same as one previously isolated by Seibert et al. (6), who assigned it a molecular weight of 32,000. The other protein was not obtained sufficiently free from polysaccharide so that its molecular weight could be determined, but it is believed to have a sedimentation constant of about 2 S. Sedimentation and diffusion constants have been obtained for the polysaccharide, which appears to be a homogeneous molecular species with a molecular weight of about 20,000. The source in unheated tuberculin of the proteins obtained from heated preparations is discussed.