{"title":"Rapid development of renal lesions in diabetic DBA mice infected with the D-variant of encephalomyocarditis virus (EMC-D).","authors":"K Doi, H Matsuzaki, T Tsuda, T Onodera","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Marked hyperglycaemia and renal lesions developed rapidly in DBA mice infected with 10 plaque-forming units of the D-variant of encephalomyocarditis virus (EMC-D). Renal alterations were demonstrated in the glomeruli, tubular epithelium and small vessels 2 months after infection. Glomerular changes were characterized by mesangial thickening due to an increase of basement membrane-like material in the mesangial matrix. Nodular glomerular lesions were commonly observed 3 months after infection, whereas distinct thickening of the glomerular basement membrane was rarely seen. Besides these glomerular changes, glycogen inclusions in the distal tubular epithelium and medial degeneration in the arterioles were also noticed. The EMC-D-infected DBA mouse appears to be a useful experimental model for the study of human diabetic nephropathy.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 3","pages":"275-81"},"PeriodicalIF":0.0,"publicationDate":"1989-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040583/pdf/brjexppathol00147-0051.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13904048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Isolation of silica-dependent protein from rat lung with special reference to development of fibrosis.","authors":"M Aalto, E Kulonen, J Pikkarainen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Silicosis was produced experimentally in rats by single intratracheal injections of various doses of SiO2 dust. The weight of the lungs as well as the contents of total nitrogen, collagen, nucleic acids (especially RNA), and lipids increased in accordance with the dose and the time interval. Fibrogenic stimulation in vitro was shown by the supernatant of the homogenized lung in the incorporation of proline into incubated granulation tissue or lung fibroblasts. The fibrogenic factor-activity depended more on the time interval after the injection than on the SiO2 dose. Electrophoresis of the soluble proteins in the silicotic rat lungs showed a protein of 16,000 Da, which was dependent on the time interval following SiO2 administration as well as on the dose itself, and which originated from macrophages. This protein was purified by repeated gel-filtration chromatography. It stimulated collagen synthesis in granulation-tissue cells at a concentration of about 10(-10) M in a dose-dependent way. It was acidic by amino acid composition but differed from calmodulin which also increased collagen synthesis in granulation-tissue cells in vitro. The ability of non-fractionated macrophage preparations to stimulate the incorporation of proline into collagen correlated inversely with the gross alkaline RNase activity.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"167-82"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040552/pdf/brjexppathol00146-0059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13687141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of foster feeding and bottle feeding expressed breast-milk on the susceptibility of guinea-pig infants to influenza virus.","authors":"H M Ali, R Scott, G L Toms","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Infant guinea-pigs born to mothers immunized against influenza virus by infection during pregnancy were reared from birth by non-immune foster mothers. As a control for the effects of fostering, a similar group were fostered to immune mothers. Fostering, regardless of the immune state of the foster-mother, increased the susceptibility of the infant to upper respiratory tract infection. Increased susceptibility was associated with ablation of the infants IgM and IgA antibody responses and reduced secretion of transplacentally acquired IgG antibody in nasal secretions. In the reciprocal experiment, infants of non-immune mothers fostered to immune mothers cleared virus more rapidly than their peers who were fed by their own mothers. This protective effect was associated with an enhanced nasal IgM and IgA antibody response. Infants of immune mothers separated from their mothers at birth and hand-reared on a cow's-milk-based formula feed suffered an increased susceptibility to the virus similar to that seen in fostered infants. Addition of a pool of expressed milk from a group of immune mothers, including their own, to the feed of hand-reared infants did not reduce their susceptibility. However, a further group of infants fed a non-cellular whey fraction of the same milk pool secreted significantly lower titres of virus. This increased protection was associated with elevated levels of IgG antibody secretion into nasal washes early in infection.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"183-91"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040548/pdf/brjexppathol00146-0075.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13872326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T Ozeki, K Imanishi, H Ueda, T Uchiyama, K Funakoshi, I Suzuki, K Ohuchi, M Kan, T Satoh
{"title":"Alpha 1-antitrypsin and hepatic fibrosis.","authors":"T Ozeki, K Imanishi, H Ueda, T Uchiyama, K Funakoshi, I Suzuki, K Ohuchi, M Kan, T Satoh","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The administration of alpha 1-antitrypsin, both sialo and asialo types, to rats with chronic liver injury accelerated hepatic fibrosis. More fibrosis was seen histologically and the amount of hydroxyproline in the liver increased. Moreover, the growth of HEL cells (human embryonal lung fibroblast) in culture was promoted by alpha 1-antitrypsin though the action of the asialo type was very weak by contrast with the sialo type.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"143-52"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040551/pdf/brjexppathol00146-0036.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13925131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M T Portolés, R Pagani, M J Ainaga, I Díaz-Laviada, A M Municio
{"title":"Lipopolysaccharide-induced insulin resistance in monolayers of cultured hepatocytes.","authors":"M T Portolés, R Pagani, M J Ainaga, I Díaz-Laviada, A M Municio","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In order to clarify the endotoxin effect on the hepatic removal of insulin, the influence of lipopolysaccharide (LPS) from E. coli 0111:B4 on the insulin binding and endocytosis in cultured hepatocytes from adult male rats has been investigated. LPS decreases both processes in a time and temperature-dependent manner, showing a major effect at short time and low temperature, according to the characteristics of LPS binding and uptake.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"199-205"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040547/pdf/brjexppathol00146-0090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13799498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P J Bugelski, C M Vockley, J M Sowinski, E Arena, B A Berkowitz, D G Morgan
{"title":"Ultrastructure of an arterial lesion induced in rats by fenoldopam mesylate, a dopaminergic vasodilator.","authors":"P J Bugelski, C M Vockley, J M Sowinski, E Arena, B A Berkowitz, D G Morgan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Fenoldopam mesylate (FM) is a dopaminergic vasodilator with demonstrated efficacy and a favourable safety profile in hypertensive and congestive heart failure patients. FM produced a novel arterial lesion in renal and splanchnic arteries of rats, but not dogs or monkeys. The studies reported here were undertaken to investigate the ultrastructure of the arterial lesion induced in rats by FM in an attempt to shed light on its pathogenesis. Rats were infused intravenously with FM, either 50 micrograms/kg/min for 1 or 4 h, or 5 or 100 micrograms/kg/min for 24 h. Control rats were infused for 4 or 24 h with vehicle alone. Perfusion-fixed tissue from the stomach and pancreas of control and drug-treated rats was examined by transmission electron microscopy. No arterial lesions were seen in rats infused with the drug for 1 or 4 h, or in control rats. All drug-treated rats infused with 5 or 100 micrograms/kg/min of FM for 24 h had lesions in subserosal gastric arteries and interlobular pancreatic arteries. In areas of mild arterial damage, medial smooth muscle cells contained intracytoplasmic pseudovacuoles, autophagic vacuoles, and electron-dense, myofilamentous inclusions. More severe lesions were characterized by overt medial necrosis and haemorrhage. The endothelium of affected arteries was invariably intact, except in areas of severe medial damage. The internal elastic lamina and connective tissue elements within the arterial wall were unaffected. These findings suggest that medial smooth muscle cells are the primary site of damage caused by fenoldopam mesylate in splanchnic arteries of the rat. This iatrogenic arterial lesion could provide an interesting model to study the response of medial smooth muscle to pharmacologically mediated injury.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"153-65"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040543/pdf/brjexppathol00146-0046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13710096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of heparin on the haemodynamic and structural response in the rat to acute and chronic hypoxia.","authors":"L M Hu, R Geggel, P Davies, L Reid","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the mouse, heparin administered intermittently, has been shown to reduce the right ventricular hypertrophy (RVH) caused by hypoxia. We have investigated in the rat the effect of heparin on the haemodynamic and pulmonary vascular structural remodelling produced by hypoxia, with special reference to the new muscularization of peripheral arteries. Heparin at one of two doses (30 and 50 u/kg/h) was administered by continuous intravenous infusion from a miniosmotic pump to rats during 10 days exposure to hypobaric hypoxia and its effect examined on mean pulmonary artery pressure (PPa), RVH and, using morphometric techniques, vascular structural remodelling. Hypoxia produced the haemodynamic and structural changes previously described in this model. Heparin had no significant effect on PPa; a slight reduction in RVH was seen in the high-dose heparin group. After heparin, the narrowing of the axial pulmonary artery lumen caused by hypoxia was less: heparin reduced the proportion of arteries that became muscularized, particularly at alveolar duct level where the pericyte is the precursor smooth muscle cell. Heparin did not diminish the increase in medial thickness or reduction in external diameter of muscular arteries. Some rats, after chronic hypoxia, did not respond to an acute hypoxic challenge yet were no different from 'responders' in other haemodynamic and structural features. Including all rats, the mean acute pressor response to hypoxia was unaffected by heparin: taking only responder rats, a trend was apparent that heparin reduced the rise in PPa on acute hypoxic challenge.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"113-24"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040541/pdf/brjexppathol00146-0006.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13872324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cell cycle dependence of N-methyl-N-nitrosourea-induced tumour development in the proliferating, partially resected rat urinary bladder.","authors":"E Kunze, T Graewe, S Scherber, J Weber, P Gellhar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In the present experiments the dependence of tumour induction upon the different phases of the cell cycle in the proliferating urinary bladder was examined. For stimulation of urothelial proliferation, a one-third resection of the bladder was performed in female Wistar rats. To synchronize the proliferating urothelial cells, hydroxyurea (HU) was given in 23 fractionated, consecutive intraperitoneal doses (0.1 mg/g body weight each) at hourly intervals shortly prior to and during maximal proliferation (between 33 and 55 h following partial cystectomy). The direct-acting urothelial carcinogen N-methyl-N-nitrosourea (MNU) was administered as a single, intravesicular pulse dose (5 mg/kg body weight) during the different cell cycle phases and to control animals with a non-resected, quiescent bladder (G0-phase). The incidence of urothelial bladder tumours was 32.6% in the controls. By comparison, the tumour incidences were 18.9, 9.3, 21.7, 26.3, 25.0 and 30.0%, respectively, when MNU was instilled during the late G1-, early and late S-, G2 + M-, and the early and late postmitotic phase. The results obtained from a total of 283 rats thus clearly document a cell-cycle-specific inhibition of MNU-induced tumour development in the proliferating urinary bladder, particularly when the carcinogen was administered during the early S-phase (P less than 0.016). There were no differences in the histology and extension of the urothelial bladder tumours found in the different experimental groups. MNU has also been shown to produce urothelial tumours in the renal pelvis (overall tumour incidence: 3.2%) and ureters (1.4%) as well as mesenchymal tumours in the bladder (4.9%) and kidneys (1.4%). Conclusions are tentatively drawn about the mechanisms underlying the observed cell-cycle-specific inhibition of urothelial carcinogenesis.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"125-42"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040540/pdf/brjexppathol00146-0018.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13872325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A R Coates, H Nicolai, M J Pallen, A Guy, S D Chaparas, D A Mitchison
{"title":"The 45 kilodalton molecule of Mycobacterium tuberculosis identified by immunoblotting and monoclonal antibodies as antigenic in patients with tuberculosis.","authors":"A R Coates, H Nicolai, M J Pallen, A Guy, S D Chaparas, D A Mitchison","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The object of this study was to discover new M. tuberculosis antigens which are recognized by patients with tuberculosis, because effective serodiagnostic tests are likely to require combinations of different antigens. In our early experiments using immunoblotting, the findings suggested that human sera from smear-negative tuberculosis patients bound to an antigen in the 45 kDa region. Subsequently, estimates of molecular weight in the immunoblots confirmed that the murine monoclonal antibody (MAB) HGT-6 and sera from patients both recognized the same 45 kDa molecule. An antibody-antibody competition assay between MAB HGT-6 and sera from smear-positive tuberculosis patients yielded a positive result in 23 out of 43 sera from patients, but in only four out of 23 from controls. This is further evidence that the 45 kDa antigen is recognized by tuberculous patients. We analysed whether a combination of the 45 kDa antigen results and those of known antigens might better discriminate between minimal smear-negative disease and healthy controls than could test with single antigens. There is no clinically useful laboratory test for smear-negative tuberculosis. In immunoblotting, combining the results with the 65, 45, 38 and 10 kDa antigens gave the best discrimination. This suggests that future serodiagnostic tests for minimal disease, such as the antibody-antibody competition assay, should contain a MAB against the 45 kDa antigen and possibly also against the 10 kDa antigen.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 2","pages":"215-25"},"PeriodicalIF":0.0,"publicationDate":"1989-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040542/pdf/brjexppathol00146-0104.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13644549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}