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PubMed1977

On the lysosomal function of juxtaglomerular granules.

The presence of acid phosphatase, beta-glucuronidase and aryl sulfatase in juxtaglomerular cell granules (JGG) as well as the uptake and concentration of certain low molecular weight dyes by these granules have repeatedly suggested that they are akin to lysosomes. In the present experiments, rats were injected with three substances of widely different molecular weight and physicochemical properties--sucrose, iron sorbitol-citric acid complex (Jectofer) and horseradish peroxidase--that are well known to selectively concentrate in renal tubular cell lysosomes. None of these substances was found to enter the JGG to any significant degree, although both sucrose and Jectofer were evident in juxtaglomerular cells. Contrary to previous reports, thorium dioxide (Thorotrast) particles were not detected in the JGG after parenteral injection. These results indicate that JGG do not possess any significant lysosomal function and raise the question of the role of hydrolytic enzymes in the physiology of these granules.

Acid Phosphatase↗
PubMed2000

Surgical treatment of adult primary hepatic sarcoma.

BACKGROUND: Primary sarcomas of the liver are extremely rare in adults. Optimal therapeutic approaches remain unclear. METHODS: Twenty consecutive adult patients who had surgical treatment for primary hepatic sarcomas were reviewed. Patient age ranged from 23 to 80 years. Other than one patient with primary hepatic angiosarcoma who had a history of thorium dioxide colloid (Thorotrast) exposure 23 years before diagnosis, no predisposing causes were apparent. Nineteen patients had hepatic resection and one patient had an orthotopic liver transplant. No patient received neoadjuvant chemotherapy or radiotherapy but radiotherapy was delivered intraoperatively in one patient. RESULTS: Leiomyosarcoma was the most common histological type of sarcoma diagnosed (five of 20 patients), followed by malignant solitary fibrous tumour (four) and epithelioid haemangioendothelioma (three). Fourteen tumours were high-grade sarcomas and six were low grade malignancies. Thirteen patients developed a recurrence. Distant metastases (ten patients) and intrahepatic recurrence (six) were the predominant sites of initial treatment failure. Six patients received salvage chemotherapy. Histological grade was the only factor significantly associated with overall patient survival (P= 0.03). With complete resection, patients with high-grade tumours had a 5-year survival rate of 18 (95 per cent confidence interval 5-62) per cent compared with 80 (52-100) per cent for patients with low-grade tumours. The 5-year survival rate for all 20 patients was 37 (20-60) per cent. CONCLUSION: Surgical resection is the only effective therapy for primary hepatic sarcomas at present. Better adjuvant therapy is necessary, especially for high-grade malignancies, owing to the high failure rate with operation alone.

Adult↗
PubMed1962

Studies on the cornea. II. The uptake and transport of colloidal particles by the living rabbit cornea in vitro.

In vitro studies of the transport of colloidal particles by the cornea were carried out on intact corneas of adult rabbits in a chamber described by Donn, Maurice, and Mills (2) in which the epithelial or the endothelial surface of the cornea was exposed to thorium dioxide or saccharated iron oxide under various conditions. These studies confirmed the results of previous work in vivo and allowed modification of the experimental conditions. Particles are pinocytosed at the apical surface of the corneal endothelium and carried around the terminal bar in membrane-bounded vesicles. Basal to the terminal bar these vesicles fuse with the lateral cell margin and their contents are released into the intercellular space, in which they appear to be carried by a one-way flow down to Descemet's membrane and the corneal stroma. Indications that the endothelial transport is an active process are presented by the different pathways of transport into or out of the corneal stroma, as well as by the approximately 70 per cent reduction in transport activity at low temperatures.

Animals↗
PubMed1956

Uptake and transfer of particulate matter from the peritoneal cavity of the rat.

1. Colloidal mercuric sulfide or thorium dioxide injected intraperitoneally passes into the cytoplasm of the mesothelium of the mesentery and of the diaphragm as early as 15 to 30 minutes after the injection. 2. Between 15 minutes and 12(1/2) hours the number of particles within the mesothelial cells increases as the time between injection and termination of the experiment is lengthened. 3. The particulate matter is usually localized in the cytoplasm within clear vacuoles or bodies having a relatively dense matrix. 4. A greater quantity of the absorbed material is commonly observed within the cytoplasm of the diaphragmatic than of the mesenteric mesothelium.

Abdominal Muscles↗
PubMed1978

Retrieval and recycling of synaptic vesicle membrane in pinched-off nerve terminals (synaptosomes).

The morphological features of pinched-off presynaptic nerve terminals (synaptosomes) from rat brain were examined with electron microscope techniques; in many experiments, an extracellular marked (horseradish peroxidase or colloidal thorium dioxide) was included in the incubation media. When incubated in physiological saline, most terminals appeared approximately spherical, and were filled with small (approximately 400-A diameter) "synaptic vesicles"; mitochondria were also present in many of the terminals. In a number of instances the region of synaptic contact, with adhering portions of the postsynaptic cell membrane and postsynaptic density, could be readily discerned. Approximately 20--30% of the terminals in our preparations exhibited clear evidence of damage, as indicated by diffuse distribution of extracellular markers in the cytoplasm; the markers appeared to be excluded from the intraterminal vesicles under these circumstances. The markers were excluded from the cytoplasm in approximately 70--80% of the terminals, which may imply that these terminals have intact plasma membranes. When the terminals were treated with depolarizing agents (veratridine or K-rich media), in the presence of Ca, many new, large (600--900-A diameter) vesicles and some coated vesicles and new vacuoles appeared. When the media contained an extracellular marker, the newly formed structures frequently were labeled with the marker. If the veratridine-depolarized terminals were subsequently treated with tetrodotoxin (to repolarize the terminals) and allowed to "recover" for 60--90 min, most of the large marker-containing vesicles disappeared, and numerous small (approximately 400-A diameter) marker-containing vesicles appeared. These observations are consistent with the idea that pinched-off presynaptic terminals contain all of the machinery necessary for vesicular exocytosis and for the retrieval and recycling of synaptic vesicle membrane. The vesicle membrane appears to be retrieval primarily in the form of large diameter vesicles which are subsequently reprocessed to form new "typical" small-diameter synaptic vesicles.

Calcium↗
PubMed1979

Effects of colchicine on endocytosis and cellular inactivation of horseradish peroxidase in cultured chondrocytes.

Horseradish peroxidase (HRP) was used as a marker to study the effects of microtubule-disruptive drugs on uptake and cellular inactivation of exogenous material in cultures of embryonic chick chondrocytes. HRP was ingested by fluid endocytosis, and intracellular enzyme activity subsequently diminished exponentially with time. Cytochemically, reaction product for HRP was found in vesicles often located close to the dictyosomes of the Golgi complex. Colchicine and vinblastine caused disappearance of cytoplasmic microtubules and disorganization of the Golgi complex with concomitant reduction in the cellular uptake of HRP to about half of that in the controls. Lumicolchicine, on the other hand, left cell fine structure and HRP uptake unaffected. These results indicate that microtubules are of considerable importance in the process of fluid endocytosis in cultured chondrocytes although the exact mechanism remains to be elucidated. The rate of intracellular inactivation of ingested HRP was not affected by colchicine or vinblastine. Double-labeling experiments with colloidal thorium dioxide and HRP likewise indicated that fusion of endocytic vesicles and lysosomes is not dependent on intact microtubules. The total specific activities of the three lysosomal enzymes examined were weakly or not at all changed by treatment of the cultures with colchicine or vinblastine. It therefore seems unlikely that microtubular organization plays an important role in the production or degradation of lysosomal enzymes in cultured chondrocytes.

Acetylglucosaminidase↗
PubMed1959

The effects of bacterial endotoxin on lipide metabolism. I. The responses of the serum lipides of rabbits to single and repeated injections of Shear's polysaccharide.

Single intravenous injections of Shear's polysaccharide in varying dosages invariably produced an elevation in the levels of the total serum lipides 24 hours after injection of endotoxin. The total serum cholesterol and lipide phosphorus were also affected, although they did not change with smaller doses of endotoxin and were rarely elevated to the same degree as were the total serum lipides. The degree of elevation of the serum lipides was apparently related to the amount of endotoxin injected up to a certain point, beyond which there was no further increase. There were two types of response to endotoxin by the serum lipides, a moderate increase and an uncontrolled increase. Higher dosages of endotoxin and fasting apparently increased the incidence of the latter response. No direct correlation could be made between serum lipide responses and histologic evidence typical of the generalized Shwartzman reaction following this regimen of endotoxin injection. The Shwartzman reaction did occur with greater frequency and with lower dosages of endotoxin in fasted animals. Animals given repeated injections of endotoxin showed an initial increase in serum lipides followed by a progressive decrease to normal levels as tolerance to the febrile action of endotoxin appeared. The febrile tolerance as well as the unresponsiveness of the serum lipides to endotoxin was abolished by thorium dioxide (thorotrast) in these animals. In similar experiments a "breakthrough" of lipide unresponsiveness to endotoxin was obtained by increasing the amount of endotoxin injected. Some of the implications of these results for the metabolic alterations produced by bacterial endotoxins are discussed.

Animals↗
PubMed1983

The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes.

The interactions between the L. pneumophila phagosome and monocyte lysosomes were investigated by prelabeling the lysosomes with thorium dioxide, an electron-opaque colloidal marker, and by acid phosphatase cytochemistry. Phagosomes containing live L. pneumophila did not fuse with secondary lysosomes at 1 h after entry into monocytes or at 4 or 8 h after entry by which time the ribosome-lined L. pneumophila replicative vacuole had formed. In contrast, the majority of phagosomes containing formalin-killed L. pneumophila, live Streptococcus pneumoniae, and live Escherichia coli had fused with secondary lysosomes by 1 h after entry into monocytes. Erythromycin, a potent inhibitor of bacterial protein synthesis, at a concentration that completely inhibits L. pneumophila intracellular multiplication, had no influence on fusion of L. pneumophila phagosomes with secondary lysosomes. However, coating live L. pneumophila with antibody or with antibody and complement partially overcame the inhibition of fusion. Also activating the monocytes promoted fusion of a small proportion of phagosomes containing live L. pneumophila with secondary lysosomes. Acid phosphatase cytochemistry revealed that phagosomes containing live L. pneumophila did not fuse with either primary or secondary lysosomes. In contrast to phagosomes containing live bacteria, the majority of phagosomes containing formalin-killed L. pneumophila were fused with lysosomes by acid phosphatase cytochemistry. The capacity of L. pneumophila to inhibit phagosome-lysosome fusion may be a critical mechanism by which the bacterium resists monocyte microbicidal effects.

Antibodies, Bacterial↗
PubMed1997

Epidemiological characteristics and risk factors of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major cancers in the world. There is a striking variation in HCC incidence rates between various countries, with a highest-to-lowest ratio of 112.5 for males and 54.7 for females. The high-risk populations are clustered in sub-Saharan Africa and eastern Asia. The male-to-female ratio for HCC ranges from < 1 to 6.4 and mostly from 2 to 4. There exist significant variations in the incidence of HCC among different ethnic groups living in the same area and among migrants of the same ethnic groups living in different areas. The age curves of HCC are significantly different in various countries, suggesting variability in exposure to risk factors. Chronic carriers of hepatitis B and C viruses (HBV and HCV, respectively) have an increased risk of HCC. The relative and attributable HCC risk of HBV and HCV carrier status varies in different countries. There exists a synergistic interaction on HCC between the two viruses. Aflatoxin exposure, cigarette smoking, heavy alcohol consumption, low vegetable intake, inorganic arsenic ingestion, radioactive thorium dioxide exposure, iron overload and the use of oral contraceptives and anabolic steroids have been documented as HCC risk factors. Recent molecular epidemiological studies have shown that low serum retinol levels as well as elevated serum levels of testosterone, neu oncoprotein and aflatoxin B1-albumin adduct are associated with an increased HCC risk. There is a synergistic interaction on HCC between chronic HBV infection and aflatoxin exposure. Familial aggregation of HCC exists and a major susceptibility gene of HCC has been hypothesized. Patients of some genetic diseases are at an increased risk of HCC. The genetic polymorphisms of cytochrome P450 2E1 and 2D6 and arylamine N-acetyltransferase 2 are associated with the development of HCC. A dose-response relationship between aflatoxin exposure and HCC has been observed among chronic HBV carriers who have null genotypes of glutathione S-transferase M1 or T1, but not among those who have non-null genotypes. Human hepatocarcinogenesis is a multistage process with the involvement of a multifactorial aetiology. Gene-environment interactions are involved in the development of HCC in humans.

Carcinoma, Hepatocellular↗
PubMed1983

Lysosomal response of a murine macrophage-like cell line persistently infected with Coxiella burnetii.

The lysosomal response of a murine macrophage-like tumor cell line (J774) during persistent infection with Coxiella burnettii was examined. By using acid phosphatase as a lysosomal marker, it was shown that phagosome-lysosome fusion occurred in J774 cells persistently infected with C. burnetii. This observation was verified using thorium dioxide, an electron-dense compound that is sequestered in secondary lysosomes. The phagolysosomes contained viable replicating rickettsiae. Spectrofluorometric analysis indicated that the phagolysosomal pH of persistently infected cells was acidic. In attempts to correlate rickettsial survival with lysosome function, the activities of several lysosomal enzymes were assayed in both infected and uninfected cells. Activities of acid phosphatase and beta-acetylglucosaminidase were not significantly altered during infection. However, infected cells appeared to display slightly higher intracellular lysozyme, beta-glucuronidase, and beta-galactosidase activities.

Acid Phosphatase↗
PubMed1984

Yersinia pestis grows within phagolysosomes in mouse peritoneal macrophages.

Transmission electron microscopy was used to determine the intracellular localization of Yersinia pestis growing within cultured resident peritoneal macrophages of mice. Monolayers fixed immediately, or as long as 4.5 h, after infection contained yersiniae closely surrounded by a membrane. The vesicles containing the yersiniae were determined to be phagolysosomes by labeling secondary lysosomes of macrophages with electron-dense particles of thorium dioxide. The presence of the label within vesicles containing yersiniae indicates that this pathogen grows within the lysosomal compartment of its target host cell.

Animals↗
PubMed2000

Coxiella burnetii exhibits morphological change and delays phagolysosomal fusion after internalization by J774A.1 cells.

Coxiella burnetii, the etiological agent of Q fever, is an obligate intracellular bacterium proliferating within the harsh environment of the phagolysosome. Mechanisms controlling trafficking to, and survival of pathogens within, the phagolysosome are unknown. Two distinct morphological variants have been implicated as playing a role in C. burnetii survival. The dormant small-cell variant (SCV) is resistant to extracellular stresses and the more metabolically active large-cell variant (LCV) is sensitive to environmental stresses. To document changes in the ratio of SCVs to LCVs in response to environment, a protein specific to SCV, ScvA, was quantitated. During the first 2 h after internalization of C. burnetii by J774A.1 cells, the level of ScvA decreased, indicating a change from a population containing primarily SCVs to one containing primarily LCVs. In vitro experiments showed that 2 h of incubation at pH 5.5 caused a significant decrease in ScvA in contrast to incubation at pH 4.5. Measuring in vitro internalization of [(35)S]methionine-[(35)S]cysteine in response to pH, we found the uptake to be optimal at pH 5.5. To explore the possibility that after uptake C. burnetii was able to delay phagolysosomal fusion, we used thorium dioxide and acid phosphatase to label phagolysosomes during infection of J774A.1 cells. We determined that viable C. burnetii was able to delay phagolysosomal fusion. This is the first time that a delay in phagolysosomal fusion has been shown to be a part of the infection process of this pathogenic microorganism.

Animals↗
PubMed1980

Angiosarcoma of the liver: annual occurrence and aetiology in Great Britain.

The annual occurrence of angiosarcoma of the liver (ASL) in Britain from 1963 to 1977 was studied, including clinical and occupational details for those cases agreed as ASL by a panel of histopathologists. Thirty-five cases (28 men, six women, and one infant girl) were agreed as ASL. The increase in the incidence of ASL observed in recent years was attributable to Thorotrast (thorium dioxide) usage (eight cases) and exposure to vinyl chloride (two cases) in the past. In its clinical presentation and prognosis ASL resembled primary liver carcinoma, except that extrahepatic metastases were found in only eight (23%) cases, and haemoperitoneum ws more common in those cases due to Thorotrast. The results suggested a possible increased risk of ASL in the electrical and plastics fabrication industries, but information on exposure was inadequate to implicate specific chemicals. The clinical features of one case were indicative of arsenical intoxication, but medications in the other patients did not appear to be of aetiological importance.

Adult↗
PubMed1994

Malignant vascular tumors of the liver: radiologic-pathologic correlation.

Although benign vascular tumors of the liver are extremely common (hemangioma is the most common), malignant vascular tumors of the liver are very rare. In the adult, these tumors are angiosarcoma, epithelioid hemangioendothelioma, and Kaposi sarcoma. All hepatic malignant vascular tumors share histologic characteristics, grow around and into vessels, and are grossly multifocal. They may be misdiagnosed histologically, particularly if only a biopsy sample is available. Although imaging findings are often non-specific, some features are suggestive or even characteristic of these neoplasms. Such features include previous exposure to thorium dioxide (Thorotrast) in cases of angiosarcoma, coalescence of multiple nodules into large peripheral masses in epithelioid hemangioendothelioma, and association between acquired immunodeficiency syndrome and cutaneous involvement in Kaposi sarcoma. Because hepatic malignant vascular tumors are often multiple, the main differential diagnosis is metastatic disease. There is no effective treatment for these tumors, and although survival time is variable, the prognosis is generally unfavorable.

Hemangioendothelioma, Epithelioid↗
PubMed1988

Intrahepatic cholangiocarcinoma: radiologic-pathologic correlation.

Seventeen proved cases of intrahepatic cholangiocarcinoma (ICAC) were reviewed to establish a radiologic-pathologic correlation. The most common appearance of ICAC at computed tomography (CT) is that of a single, homogeneous low-attenuation mass. Multiple low-attenuation lesions were present in four cases. Calcification was depicted by CT in three cases. At angiography, ICAC has a variable appearance with avascular, hypovascular, and hypervascular patterns possible. Portal obstruction was seen in only one case. The most common appearance of ICAC at sonography is that of a homogeneously hyperechoic mass, either single or multiple. In only one case was ICAC hypoechoic. Plain abdominal radiography demonstrated calcification in three patients and evidence of Thorotrast (thorium dioxide) deposition in one. Upper gastrointestinal series demonstrated abnormal gastric folds in two cases, corresponding to gastric invasion by ICAC. There were no characteristic radiographic findings, but the following features may be helpful in differentiating ICAC from other primary intrahepatic tumors, particularly typical hepatocellular carcinoma: a homogeneously echogenic or high-attenuation appearance on images that reflects the uniform nature observed at pathologic examination, the presence of calcification, and the uncommon invasion of portal or hepatic veins. Conversely, the presence of satellite lesions may blur the the distinction between ICAC and metastatic liver disease.

Adenoma, Bile Duct↗
PubMed1998

Primary hepatic angiosarcoma: report of a case involving environmental arsenic exposure.

Hepatic angiosarcoma is a rare malignant tumor with a rapidly fatal course. It has become a subject of interest because of its intimate relationship with environmental carcinogens, such as thorium dioxide (Thorotrast), vinyl chloride monomer, and arsenic. We describe a case of a chronic hepatitis B surface antigen carrier, with a 20-year history of environmental exposure to arsenical-containing agricultural herbicides and bactericides, who developed a hepatic angiosarcoma. He died due to rupture of the hepatic angiosarcoma with acute hemoperitoneum 9 weeks after initial diagnosis. This is a rare case of primary hepatic sarcoma, especially in Taiwan where hepatocellular carcinoma is endemic. This case not only serves to give more evidence of the relationship between hepatic angiosarcoma and arsenical exposure, but also demonstrates the key point in the differential diagnosis of liver tumors. Increased familiarity with this disease will facilitate correct diagnosis and help to improve management of the condition in the future.

Agriculture↗