{"title":"Polyisoprenoid, cholesterol and ubiquinone levels in human hepatocellular carcinomas.","authors":"I Eggens, P G Elmberger, P Löw","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The lipid composition of human hepatocellular carcinomas was examined. The level of dolichol in the tumours was decreased compared to control tissue, whereas the concentration of dolichyl phosphate did not exhibit any major change. A decrease in the amount of dolichyl ester was also observed. The pattern of individual polyisoprenoids in the free dolichol pool was changed in several carcinomas with a relative increase in the shorter dolichols. The isoprenol composition in the dolichyl ester and phosphate fractions of tumours were basically similar to those of controls. alpha-Unsaturated polyisoprenols are present in control livers at a level of 3% of the total free polyisoprenoid fraction, while this value was increased in the tumours. Similar to dolichol, the amount of ubiquinone was also decreased. The content of cholesterol was increased, while the fatty acid pattern of the dolichyl esters showed minor alterations. These modifications in lipid content indicate different mechanisms for the regulation of dolichol and dolichyl phosphate concentrations. The high levels of sterols in contrast to the low polyisoprenol content suggests interference with the regulation of the mevalonate pathway, which is the common biosynthetic route for cholesterol, ubiquinone and dolichol.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 1","pages":"83-92"},"PeriodicalIF":0.0,"publicationDate":"1989-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040537/pdf/brjexppathol00145-0091.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13682979","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":"Experimental frost-bite in Hanford Miniature Swine. I. Epithelial changes.","authors":"P Schoning, M P Hamlet","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Frost-bite lesions were produced in five Hanford Miniature Swine exposed to - 75 degrees C air for 1, 3, 5, 10 or 20 min. Biopsies were taken at 0, 3, 6, 12, 24 and 48 h and 1 and 2 weeks. Two hundred slides were evaluated microscopically: pyknosis, vacuolation, individualization of cells, and degeneration were graded from 0-5; 0, no change; 5, severe change. Necrosis, new epithelium, and microabscesses were recorded as present or absent. Early changes of vacuolation of keratinocytes, individualization of cells and pyknosis increased with biopsy time until 1 week, at which time more severe changes predominated. Intermediate changes of advanced degeneration and dermoepidermal microabscesses were seen at 48 h and 1 and 2 weeks. Late changes of necrosis and epithelial regeneration occurred, both separately or together in the same tissue, at 1 and 2 weeks. Regeneration occurred either as complete replacement of epithelium, or as crescents of new epithelium beneath degenerating epithelium. The results show that necrosis is a late development, so prognosis based on early skin biopsies must be guarded to unfavourable. Furthermore, these findings suggest that cold has a direct effect on epithelial cell membranes.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 1","pages":"41-9"},"PeriodicalIF":0.0,"publicationDate":"1989-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040530/pdf/brjexppathol00145-0051.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14059623","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":"Increased vascular permeability and polymorphonuclear leucocyte accumulation in vivo in response to recombinant cytokines and supernatant from cultures of human synovial cells treated with interleukin 1.","authors":"M L Watson, G P Lewis, J Westwick","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The inflammatory effects of intradermal injections of the human recombinant cytokines interleukin 1 (IL-1), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF alpha) have been assessed in rabbit skin, and compared with the effects of a novel polymorphonuclear leucocyte (PMN)-stimulating activity (PSA) produced by IL-1-treated human synovial cell cultures. IL-1 (84 fmol) and GM-CSF (10 pmol) caused increases in vascular permeability with a delayed onset, as assessed by the dermal accumulation of intravenously-administered 125I-human serum albumin. These cytokines also stimulated extravascular accumulation of PMNs. In contrast, PSA-containing supernatant caused a more rapid and prolonged increase in vascular permeability and PMN accumulation. TNF alpha (84 fmol) was unable to stimulate either of these responses. The increases in vascular permeability and PMN accumulation following IL-1 administration in vivo may be a consequence of the local generation of PMN-stimulating activity by connective tissue cells, such as the activity produced by IL-1-treated synovial cell cultures that we have described.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"70 1","pages":"93-101"},"PeriodicalIF":0.0,"publicationDate":"1989-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2040532/pdf/brjexppathol00145-0101.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13788062","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}
J Dunham, M G Chambers, M K Jasani, L Bitensky, J Chayen
{"title":"Changes in oxidative activities of chondrocytes during the early development of natural murine osteoarthritis.","authors":"J Dunham, M G Chambers, M K Jasani, L Bitensky, J Chayen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A high incidence of natural osteoarthritis of the knee joint is found in male mice of the STR/ORT strain. The condition affects mainly the medial tibial cartilage and by the age of 27 weeks most male mice of this strain show some osteoarthritic change. Analysis of the oxidative metabolism of the chondrocytes during the development of the lesion has been facilitated by the techniques of quantitative cytochemistry. The activity of glucose-6-phosphate dehydrogenase (G6PD) has been investigated as indicative of the NADPH-generating pentose-phosphate pathway; the activities of glyceraldehyde-3-phosphate (G3PD) and lactate dehydrogenase (LDH) have been studied as indicators of glycolytic activity. In young STR/ORT mice the G6PD activity of the lateral tibial cartilage was greater and more variable than in the control mice of the CBA/HT6 strain. The activity in the medial cartilage, relative to that in the lateral cartilage, decreased with age; this change was not reflected in the activities of the other enzymes. In the lateral cartilage, the expected relationship was found between the G6PD and the G3PD activities and between the LDH and the G3PD activities. In the medial cartilage, the G6PD activities were not related to the G3PD activities. The decreased proportionality of the G6PD activities in the medial cartilage as against that in the lateral cartilage was detected in mice as young as 9 weeks; by 27 weeks of age nine of the 13 mice showed marked depression of medial as against lateral G6PD activities. In contrast, only four of the 13 mice showed any overt histological charge until up to the age of 28 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"845-53"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013294/pdf/brjexppathol00006-0090.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14350206","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}
S Pugh, S E Williams, T Barton, C G Clark, M R Lewin
{"title":"Endogenous prostaglandin E2 synthesis preserved following cytoprotection by Roter (bismuth subnitrate) in the rat alcohol model of gastric ulceration.","authors":"S Pugh, S E Williams, T Barton, C G Clark, M R Lewin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The protective effect of the compound preparation Roter, principally bismuth subnitrate and the other base constituents of these tablets, magnesium carbonate and sodium bicarbonate, were assessed using the standard alcohol model of gastric ulceration in the rat. Groups of ten rats were studied with Group A as controls, Group B alcohol alone, Group C pretreatment with base components followed by alcohol, Group D pretreatment with bismuth subnitrate followed by alcohol and Group E pretreatment with full formulation Roter followed by alcohol. The study was assessed by measurement of areas of gastric ulceration and tissue prostaglandin E2 (PGE2) levels. Alcohol alone caused gross ulceration and reduction in PGE2 synthesis compared to controls (P less than 0.001). Pretreatment with tablet base gave only marginal protection whilst bismuth subnitrate gave marked protection against ulceration compared to alcohol alone (P less than 0.001). Full formulation Roter also gave marked protection against ulceration compared to alcohol alone (P less than 0.001) and this was associated with PGE2 synthesis indistinguishable from controls but significantly greater than in the alcohol alone group (P less than 0.001). It was not possible to determine whether the normal PGE2 synthesis was the cause or the result of protective effect of Roter and the accompanying reduction in ulceration. It was possible however to conclude that using this model of experimental ulceration. Roter and bismuth subnitrate are 'cytoprotective' and this was associated with the preservation of normal prostaglandin synthesis.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"833-8"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013292/pdf/brjexppathol00006-0078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14347689","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}
E Claassen, Y Westerhof, B Versluis, N Kors, M Schellekens, N van Rooijen
{"title":"Effects of chronic injection of sphingomyelin-containing liposomes on lymphoid and non-lymphoid cells in the spleen. Transient suppression of marginal zone macrophages.","authors":"E Claassen, Y Westerhof, B Versluis, N Kors, M Schellekens, N van Rooijen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mice were injected with sphingomyelin/cholesterol or phosphatidylcholine/cholesterol (PC/C) liposomes, from twice up to 10 times, on alternate days. Administration of sphingomyelin/cholesterol (SM/C) liposomes gave rise to hepato and splenomegaly, microgranulomatous infections and changes in macrophage numbers and activity in spleen and liver. Enzyme and immuno-cytochemical methods were used, to demonstrate the effect of liposomes on the lymphoid and non-lymphoid cell populations, on cryostat sections of the spleen. Routine histological staining, of sphingomyelin/cholesterol treated animals, showed no drastic changes in morphology or compartmentalization of the spleen, apart from a small enlargement (with some microgranulomas) of the red pulp. No significant differences were found in the presence or localization of T-helper, T-cytotoxic/suppressor, T-total-lymphocytes, B-total-lymphocytes, red pulp macrophages, marginal metallophils, or non-lymphoid dendritic cells. However, a transient suppression of cells expressing marginal zone macrophage surface marker ERTR-9, was observed between the second and eighth (intravenous) administration of sphingomyelin/cholesterol liposomes. Immunization of these animals with trinitrophenyl (TNP)-ficoll, a thymus-independent type-2 antigen which is specifically processed by marginal zone macrophages (MZM), showed that these cells were not suppressed with regard to their immunological function. We conclude that chronic administration of sphingomyelin liposomes influences macrophages, probably through a general phagocytic-system overload, but not permanent or damaging changes in splenic cell populations or immunological functions occur.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"865-75"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013293/pdf/brjexppathol00006-0109.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14350207","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":"Significance of cyclosporin-A-associated renal surface irregularities.","authors":"J Cornish, M Vanderwee, G Findon, T Miller","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The purpose of this study was to investigate unusual irregularities observed on the surface of kidneys from rats which had been treated with seven 'clinically effective doses' (25 or 50 mg/kg) of cyclosporin A (CsA). Surface corrugations were obvious on gross examination and were a universal finding in our study which involved greater than 50 rats. Examination by scanning electron microscopy (SEM) showed that the surface irregularities resulted from swollen peritubular capillaries adjacent to vacuolized and partially collapsed tubules at the cortical surface. The enlarged capillaries were associated with vascular congestion, and although peritubular capillary congestion has been recognized in CsA-treated patients, it has been difficult to determine whether this reaction is associated with drug toxicity or graft rejection. Our findings, indicating that peritubular capillary congestion in addition to vacuolization and collapse of subcapsular tubules is a drug-associated phenomenon, may help give a more accurate assessment of biopsy and autopsy material from CsA-treated patients and laboratory animals.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"839-44"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013300/pdf/brjexppathol00006-0084.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14347690","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":"Mouse interstitial lung disease and pleuritis induction by human Mollicute-like organisms.","authors":"E Wirostko, L A Johnson, W J Wirostko","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mollicute-Like Organisms (MLO) are cell-wall deficient intracellular bacterial pathogens. As MLO are non-cultivable, detection is based on finding typical Mollicute bodies within the host cell using a transmission electron microscope. Extracellular Mollicutes cause disease by a variety of mechanisms. MLO cause disease by similar mechanisms, and in addition directly alter the host cell nucleus, replace the cytoplasm, and destroy the organelles. MLO parasitization of plant cells causes a well studied chronic vascular disease reversible by tetracycline antibiotics. Recently similar MLO were reported to cause human chronic ocular vasculitis. As it parasitizes, lyses, and destroys leucocytes, it has been termed Leucocytoclastic MLO. Inoculation of this MLO into mouse eyelids produced delayed onset chronic ocular and lethal cardiac vasculitis. All lesions demonstrated tissue lysis with leucocytic infiltrates and MLO parasitized leucocytes. MLO-caused human and mouse disease responds to Rifampin. This report describes the 40 interstitial lung disease lesions in 21 of 100 of those MLO inoculated mice vs 0 in 200 controls (P less than 0.05) and 27 pleuritis lesions in 17 mice vs 0 control mice (P less than 0.05). The lung and pleural disease were associated in 13 lesions and unassociated in 41 lesions. MLO parasitized leucocytes were found in both the lung and pleural lesions from six of six MLO inoculated mice versus none of six controls. As most human interstitial lung and pleural diseases are idiopathic and closely resemble this mouse disease, they may be induced by MLO and treatable by Rifampin.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"891-902"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013284/pdf/brjexppathol00006-0133.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14350208","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":"Effect of fasting on aggregation of hepatocyte rough endoplasmic reticulum in adrenalectomized and 3'MeDAB-treated rats: quantitative electron microscope study.","authors":"D J Winton, B Flaks","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A method for the quantitative analysis of the degree to which hepatocyte rough endoplasmic reticulum (ER) is arranged into parallel arrays was used to study the effect of fasting on rough ER aggregation in rat liver cells following either bilateral adrenalectomy or administration of the carcinogenic azo dye 3'-methyl-4-dimethylaminoazobenzene (3'MeDAB). One group of male inbred Leeds strain rats was subjected to bilateral adrenalectomy (ADX): after 1 week half of the animals were fasted for 24 h whereupon the whole group was killed. A second group of rats, fed for 4 weeks on a diet containing 0.06% of the carcinogenic azo dye 3'MeDAB, was similarly divided into two groups that were killed either with or without a prior 24-h fast. Untreated control groups of rats, both fasted and unfasted, were also killed. A quantitative electron microscope study was carried out to investigate the effect of each treatment on the degree to which the hepatocyte rough ER was aggregated into parallel arrays. ADX alone was without effect but caused a dramatic fall in rough ER aggregation when combined with fasting. At least as great an effect was induced by 3'MeDAB, with or without fasting, while fasting alone had a significant but much more modest effect than either ADX or the carcinogen. Thus, two disparate treatments induced morphologically identical responses in hepatocyte rough ER. The implications of this are discussed in terms of known interrelations between glucocorticoids and chemical carcinogenesis in the rat liver.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"877-89"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013291/pdf/brjexppathol00006-0120.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14275627","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":"Streptococcal necrotizing fasciitis: development of an animal model to study its pathogenesis.","authors":"D V Seal, D Kingston","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Necrotizing fasciitis is a serious and increasingly common human disease which can be caused by an infection with beta-haemolytic streptococci (BHS) of Lancefield groups A, C or G, spreading rapidly in the loose connective tissue over the muscle fascia. To facilitate study of its pathogenesis, we have developed an animal model for the production of a spreading infection with BHS in the loose connective tissue over the muscle layer in the skin of New Zealand White rabbits. Intradermal injection of group A BHS alone into the flank was unsatisfactory in that a spreading lesion occurred on only 12% of occasions. When the group A BHS were co-injected with cultures of Staphylococcus aureus, the results depended on the strain of S. aureus used: an abscess-producing strain isolated from pigs gave rise to a spreading lesion on 50% of occasions. When BHS were injected with the alpha-lysin of S. aureus at a titre which produced inflammation without necrosis, spreading lesions occurred on 75% of occasions. However, both inoculated and uninoculated broth acted synergistically with the alpha-lysin in potentiating the spread of the streptococci. This demonstration of synergy between BHS and alpha-lysin of S. aureus may reflect the clinical situation in the human, as both organisms have been found to occur together at sites where spreading streptococcal infections have originated.</p>","PeriodicalId":9248,"journal":{"name":"British journal of experimental pathology","volume":"69 6","pages":"813-31"},"PeriodicalIF":0.0,"publicationDate":"1988-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2013287/pdf/brjexppathol00006-0059.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"14347688","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}