Showing papers on "Fibrosis published in 1974"

The pathogenesis of bleomycin-induced pulmonary fibrosis in mice.

Abstract: Administration of 0.5 mg bleomycin to mice twice weekly for 4 weeks induced pulmonary fibrosis. The initial site of injury was the intima of pulmonary arteries and veins where endothelial cells became edematous and were separated from the underlying basement membrane by large blebs. These lesions occurred after 2 weeks and were associated with infiltration of perivascular spaces by lymphocytes and plasma cells. Capillary endothelial blebbing and interstitial edema were observed after 4 weeks, when multifocal necrosis of type 1 alveolar epithelial cells was accompanied by fibrinous exudation into the alveoli. The process of repair was characterized by proliferation and metaplasia of type 2 epithelial cells, fibroblastic organization of alveolar fibrin and fibrosis of the interstitium within 8 to 12 weeks. The consistent induction of changes similar to those of diffuse pulmonary fibrosis or fibrosing alveolitis in man suggests that bleomycin-induced injury may provide a suitable model for the investigation of this ill-defined group of diseases.

Hepatic Injury from Chronic Hypervitaminosis a Resulting in Portal Hypertension and Ascites

Abstract: Chronic hypervitaminosis A was diagnosed in two patients who were initially seen because of ascites and clinical signs of cirrhosis. Histologic examination of liver-biopsy material revealed perisinusoidal fibrosis, central-vein sclerosis and focal congestion associated with perisinusoidal lipid-storage cells. Vitamin A fluorescence was found on frozen sections, and direct assay of tissue revealed substantial increases in vitamin A content (1700 to 2200 μg per gram of wet liver). Electron microscopy demonstrated an increase in basement-membrane-like material and collagen within the perisinusoidal space in association with lipid-filled Ito cells. The nature of this unusual lesion suggested that it might obstruct hepatic blood flow, result in considerable parenchymal-cell atrophy and lead to portal hypertension. These findings suggest that chronic ingestion of large amounts of vitamin A stimulates fibrogenesis and results in a disorder of hepatic function resembling cirrhosis. (N Engl J Med 291:435–...

Ultrastructural Changes in Livers of Two Patients with Hypervitaminosis A

Abstract: The principal distinctive ultrastructural changes observed in the livers of 2 patients with chronic hypervitaminosis A were perisinusoidal fibrosis and massive accumulation of lipid-storing cells (Ito cells). The fibrosis consisted of a network of basement membranes with numerous bundles of collagen and reticulum fibrils. This network contained numerous Ito cells, and moderate numbers of lymphocytes, macrophoges and other mesenchymal cells. Impairment of blood flow by perisinusoidal fibrosis probably resulted in the secondary alterations in hepatocytes which included cellular atrophy and formation of cytoplasmic bullae.

Excess late subcutaneous fibrosis after irradiation of pig skin, consequent upon the application of the NSD formula.

Abstract: The development of subcutaneous fibrosis after X irradiation in courses of 1, 6 or 30 fractions has been studied quantitatively in the domestic pig. The NSD formula fails to predict the correct variation in dose for changes in the number of fractions so as to produce comparable levels of connective tissue damage even over the clinically used range from 6f./18d. to 3Of./39d.; the error in the prediction may amount to an excess dose of circa 30 per cent. The slope the iso-effect curve between 6 and 30 fractions is 0·46, compared with the combined fractionation and time factors of 0·33 in the NSD formula. The degree of late fibrosis did not correlate with the severity of the early skin reaction. The results suggest that the NSD formula is not suitable for use when planning new treatment schedules in which the number of dose fractions is reduced.

Constrictive fibrosis following silicone implants in mammary augmentation

Abstract: Constrictive fibrosis is a frequent and often grave complication of mammary augmentation with Silicone implants. In addition to tension or pressure, which lead to local callus formation and the rare apathogenic infection which is followed by tissue reaction, constrictive fibrosis is initiated by phagocytosis of Silicone particles from the surface of the implants.

Paraquat lung: a reappraisal

Abstract: Smith, P. and Heath, D. (1974).Thorax, 29, 643-653. Paraquat lung: a reappraisal. The histopathology of the lungs from four human cases of paraquat poisoning is described. In two of them there was a dense mass of fibroblastic tissue which obliterated the lung architecture, and one of these showed an extensive deposit of collagen with honeycomb change. In a third case pulmonary fibrosis was less severe and could be demonstrated exclusively within the alveolar spaces. The fourth showed earlier lesions of capillary congestion, alveolar oedema, and hyaline membrane formation. We suggest that paraquat produces the same effect on the lung in man as in the rat, namely a diffuse, cellular, intra-alveolar fibrosis. The intra-alveolar origin of this fibrosis is often obscured in the advanced stage of the disease and has been misinterpreted as fibrosing alveolitis. This fibrosis is associated with a pulmonary vascular disease. In assessing the histopathology of the lung in paraquat poisoning a history of oxygen therapy must be taken into account, for prolonged exposure to this gas may in itself induce pulmonary fibrosis.

Airway function in chronic pulmonary sarcoidosis with fibrosis.

Abstract: Sixteen patients with pulmonary fibrosis due to chronic sarcoidosis were studied for evidence of impaired airway function using conventional spirometric indices of air flow, functional residual cap...

A histochemical study on the activity of gamma-glutamyl transpeptidase in liver disease.

Abstract: Comparative histochemical study for γ-GTP and alkaline phos-phatase was performed in several disorders of liver. Areas of extensively proliferated fibrosis in chronic active hepatitis and areas of newly formed fibrosis in cirrhosis showed prominent activity of γ-GTP but poor activity for alkaline phosphatase. On the other hand, alkaline phosphatase activity was remarkably high in the connective tissue around proliferating bile ductules. Activity of both enzymes was prominent in the bile canaliculi and sinusoidal walls in obstructive jaundice, but marked decrease or loss of activity of the enzymes was observed in the degenerated or necrotic areas. While fatty degeneration of hepatocytes showed no increase in activity of the enzymes, prominent activity of γ-GTP was noted in the connective tissue surrounding degenerated hepatocytes in alcoholic liver disease. There was marked activity of γ-GTP in most tumor cells of hepatoma, while in metastatic tumor the activity of both enzymes was noted in only bile canaliculi and sinusoidal wall adjacent to the tumor.

The Apical Cap

Abstract: Nonspecific thickening of the apical visceral pleura and subpleural lung associated with fibrosis and sometimes with calcification, was found in 20.3% of cases. This thickening could not be shown histologically to be the result of tuberculosis. The frequency of such scarring increased significantly with age. Such localized pleural thickening may be related to healing of pulmonary disease in the presence of chronic ischemia. This subpleural scarring appears to be the cause of the apical cap shadow reported by many authors; other possibilities include (a) irregular projection of the lung into the overlying soft tissues and (b) other apical pulmonary disease.

Cryosurgery of respiratory structures. II. Cryonecrosis of the lung.

Abstract: This study was undertaken in dogs and monkeys to assess the sequelae of cryosurgery of the lung. In seven animals, a cryoprobe was repeatedly applied to the entire right middle lobe. In no instance was the probe inserted through the pleura into pulmonary parenchyma, but the pulmonary parenchyma was firmly compressed beneath the probe tip during freezing. This permitted through-and-through freezing of the entire right middle lobe and ensured complete cryonecrosis of the entire lobe. In three animals, a portion of the right lower lobe was also frozen by repeatedly applying the probe tip to the midportion of that lobe. All animals survived the procedures, and all resumed normal activity within 24 hours of operation. There were no pleural space complications except for the production of pleural adhesions. All lesions had the features of an acute hemorrhagic infarct, characterized by intense local hemorrhage and complete coagulation necrosis, typical of cryolesions. Subsequently, there was total collapse and fibrosis of underlying pulmonary tissue with areas of hemorrhagic necrosis, hemosiderin in macrocytes, focal calcification, and hyalinization. Serum lactic dehydrogenase values and leukocyte counts promptly increased after cryosurgery; however, all values returned to normal within 14 days, and no significant changes were noted thereafter. Thoracic roentgenograms showed changes consistent with consolidation of the right middle lobe, and by seven weeks, the only roentgeno-graphic evidence of the cryotreated middle lobe was a small density in the hilus. Histologically, this was a small mass of scarified tissue that sealed the bronchial stump and major vessels at the hilus and consisted of organized fibrosis.

Impaired Left Ventricular Contractility in Ischemic Heart Disease: Angiographic and Histopathologic Correlations

Abstract: Ventricles of 21 patients with coronary artery disease examined by coronary angiography and left ventriculography were studied histologically. The amount of fibrosis was compared to the decrease in function indicated by ventriculography, elevation of left ventricular end diastolic pressure (LVEDP), and reduction of ejection fraction. In 51% of ventricular segments dysfunction paralleled the presence or absence of fibrosis. In 42%, dysfunction, more severe than the fibrosis, was due to ischemia or coronary steal. Patchy fibrosis in 7% did not significantly decrease function. Severe decrease in ejection fraction and elevation of LVEDP may be due to ischemia not fibrosis.

Changes in Pulmonary Compliance and Production of Fibrosis in X-Irradiated Lungs of Rats

Abstract: Changes in expansibility of the lungs and thorax after single-fraction x-irradiation of the chest in rats were measured for exposures up to 3,000 R. Six weeks after irradiation, compliance was found to be markedly reduced from normal values for exposures above 1,500 R, as measured by the slope of the pressure-volume curve. Trichrome staining demonstrated no increase in collagen related to pulmonary fibrosis.

Pharmacology of fibrosis and tissue injury.

Abstract: Methods controlling tissue fibrosis are classified into those specifically inhibiting various metabolic aspects of collagen selectively in the injured tissue (ascorbic acid deficiency, effect of agent chelating Fe(2+), proline analogs, lathyrogens). The most promising method seems to be the blocking of crosslinks formation among collagen molecules by beta-aminopropionitrile, a competitive inhibitor of a crosslinking enzyme, lysyl oxidase. The second group of methods is called nonspecific, as they affect any stage of inflammatory process preceding the activation of fibroblasts. The importance of activated macrophages in the stimulation of fibroblast is discussed. Finally, a new concept is proposed, indicating the function of zinc ions in the control of the integrity of biomembrances, tissue reactivity to noxious agents. It is suggested that zinc may control NADPH dependent lipid peroxidation at the membrane level by inhibiting NADPH oxidase activity. The implication of these ideas to lung fibrosis induced by silica or asbestos is discussed.

Malignant Hypertension: Current Modes of Therapy

Abstract: The story of human hypertension research really begins in 1836 as a by-product of Richard Bright's1investigations into the association of albuminuria and dropsy, which developed the broad concept of systemic vascular disease. In 1872, Gull and Sutton2formulated the concept that a vascular disease, which they called "arterio-capillary fibrosis," was present as the "primary and essential condition in the morbid state called chronic Bright's disease with contracted kidneys." A new era in the study of hypertension began in 1879 with Frederick Horatio Akbar Mahomed's3,4report on the first systematic investigation of blood pressure during life. He observed that elevation in blood pressure may either precede or follow renal disease, and he proposed the concept that "what is the cause in one case may be the result in another." That hypertension may occur independent of renal disease and may pursue a variable course was reported by three

Amniogenic bands as a cause of syndactyly in a young human fetus.

Abstract: A fetus spontaneously aborted in the 4th month of gestation is described. The fetus displayed nonsymmetrical syndactyly of both hands and partial amputation of fingers in one hand caused by a dense tissue microscopically found to be composed of multiple folds of amnion. The placenta was examined, and showed severe pathology: multiple hematomas, infarctions, and fibrosis. The possible mode of formation of amniogenic bands is discussed and correlated with the clinical history and pathology of the placenta and membranes.

Congenital hepatic fibrosis. Two cases simulating hepatic cirrhosis.

Abstract: Congenital hepatic fibrosis (CHF) was detected in a 10-year-old boy with hepatosplenomegaly and leukopenia and in a 45-year-old man with hepatomegaly. Several years after these original findings, both patients developed bleeding that was attributed to esophageal varices and were treated by elective portasystemic shunts. In both, the preshunt liver function tests were essentially normal and the liver scans revealed homogeneous uptake. The gross aspect of the livers at laparotomy was indistinguishable from that of cirrhosis, and the liver wedge biopsies showed generalized portal and interlobular fibrosis and bile-duct hyperplasia but no evidence of previous liver-cell necrosis. Hepatic vein catheterization and portal venography in the adult patient indicated intrahepatic presinusoidal block. Neither patient had jaundice, ascites, or polycystic kidneys. Both cases appear sporadic.

Effect of operative ischemia time on survival of rat renal allografts.

Abstract: SUMMARY The influence of operative ischemia time on the survival and function in (Lewis × Brown Norway) F1 (LEW × BN) hybrid rat kidneys was studied in Lewis recipients. Thirteen bilaterally nephrectomized rats were allografted with a hybrid kidney using a modified microvascular technique. Total operative ischemia time was kept below 25 min (short ischemia time group). Fourteen additional animals were allografted with kidneys kept in saline for 45 min at 4 C before grafting (total ischemia time 60–75 min). Animals in the long ischemia time group survived over twice as long as those in the short ischemia group (median survival time 41 days versus 12 days, P < 0.001). In the short ischemia time group, the blood urea nitrogen rose progressively after transplantation. In the long ischemia time group, it rose until the 7th to 11th days after transplantation, then fell to levels 2 to 3 times normal, then rose again progressively until the death of the animals. All allografted kidneys showed histological signs of acute rejection; the long ischemia time group showed additional changes of chronic rejection with hyalinization of glomeruli and fibrosis of small arterioles. Animals in both groups showed a rise in anti-BN hemagglutinating and cytotoxic antibodies, but there was no correlation between antibody titer and graft survival. Prolongation of operative ischemia time to a degree which does not directly impair graft function may nevertheless alter graft immunogenicity by effects on passenger leukocytes, or may foster release of surface antigens leading to immunological self-enhancement.

Developement of Hepatocellular Carcinoma from Chronic Hepatitis with Mild Fibrosis

Abstract: 肝炎性肝硬変の約半数にヘパトームが発生するが,脂肪性肝硬変やその他の肝硬変にヘパトームが発生することは稀れである.また,ヘパトームの症例の40%にHB抗原が見出されるなど,肝炎ウイルスとヘパトームは密接な関係がある.しかし従来ヘパトームは肝硬変症の経過中,肝細胞が破壊と再生を繰返すうちに発生すると考えられて来た.たしかにヘパトームの86%は肝硬変を伴っているが,8%は軽い肝線維症を伴っている.本研究はこのようなヘパトームに伴う肝線維症の成因を明らかにする為に,肝組織をもちいて色素による染色法でHB抗原の検索を行なった.その結果40%の症例の非癌部にHB抗原が見出された.つまりこの肝線維症のあるものは慢性肝炎であり,ヘパトームは肝炎から肝硬変ができ上った状態に発生するばかりでなく,軽い線維化を示す慢性肝炎にも発生し得ることが明らかになった.

Allografted lungs in matched dogs with induced pulmonary hypertension

Abstract: Induction of chronic pulmonary hypertension in dogs treated by lung allotrans-plantation was performed in this study. Eight adult dogs, 3 mongrels and 5 purebred sibling foxhounds matched by mixed leukocyte culture, comprised group I and were subjected to recurrent macroembolization and compared to another group (II) of 8 unmatched normotensive animals who received allografts and immunosuppressive therapy. Findings in early biopsy specimens in the group I animals revealed endothelial edema. A mononuclear vasculitis, more marked around the veins, and a mononuclear chronic inflammatory infiltrate in the bronchial wall were additional findings in the early biopsy specimens. In the group I late biopsy specimens, electron-dense and electron-lucent endothelial cells and multilamination of the basement membrane were characteristic features. Fibrosis of the bronchial wall structures was noted during this time period, as was alveolar wall fibrosis. These pathologic endothelial lesions, the basement membrane multi-lamination and the alveolar wall fibrosis are similar to the lesions reported in the chronically rejected renal allograft.