SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
We describe a 40-year-old woman with systemic scleroderma who had hundreds of firm nodules that developed on the trunk and upper extremities during several months. We briefly review previously reported cases of this rare variant of scleroderma.
The carcinogenic activity of clivorine, a pyrrolizidine alkaloid isolated from Ligularia dentata, was studied in inbred ACI rats. Twelve animals in the experimental group received a 0.005% solution of clivorine in drinking water for 340 days and survived beyond 440 days after the beginning of the experiment. Of this group, 8 developed tumors in the liver; 2 developed hemangioendothelial sarcomas, and 6 developed neoplastic nodules. The hemangioendothelial sarcoma showed metastasis in the lung of one rat. No tumors were observed in the liver of the control animals.
This study assesses the effect of reduced glutathione (GSH) on regenerating liver, 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB) hepatocarcinogenesis, and normal and transformed hepatocytes in vitro. GSH administered intragastrically caused only a 30% reduction in thymidine incorporation into liver DNA at 24 h after partial hepatectomy; there was no apparent effect on RNA and protein synthesis. Furthermore, in 3'-MDAB induced hepatocarcinogenesis, all GSH-treated animals developed hepatocyte nodules, and serum alpha-fetoprotein (AFP) levels were not reduced. In vitro, GSH was shown to be cytotoxic to both normal and transformed hepatocytes at serum concentrations under 10%. GSH inhibited [3H]thymidine incorporation slightly in 2 transformed hepatocyte lines, but not in normal hepatocytes.
The present study was designed to determine whether orotic acid, a liver tumor promoter in the rat, also promotes liver carcinogenesis in the mouse. Eight-week-old male BALB/c mice were initiated with diethylnitrosamine (90 mg/kg i.p.). One week later they were divided into 2 groups and given either a basal diet or the basal diet containing 1% orotic acid (OA). They were killed at 6 or 10 months after the administration of the carcinogen. At 6 months, no nodular lesions were seen in mice whether or not they were exposed to OA. However by 10 months 100% of mice in both groups developed hepatic nodules. OA neither shortened the latent period for the appearance of the nodular lesions not did it increase the size of the nodules. Although BALB/c mice exhibited an increase in uridine nucleotides and a decrease in adenosine nucleotides in the liver upon exposure to OA, the magnitude of the change was less compared with that seen in the rat liver. The resistance of BALB/c mouse to the tumor-promoting effects of OA may reflect in part the resistance of the mouse to OA-induced nucleotide pool imbalance.
Several enzymes metabolize the toxic aldehydes produced during lipid peroxidation, such as 4-hydroxynonenal. During carcinogenesis induced by diethylnitrosamine in rat liver, an increase in aldehyde dehydrogenase, in comparison with normal liver, has already been shown. This paper demonstrates that, although to a lesser extent than aldehyde dehydrogenase, aldehyde reductase and glutathione-S-transferase also increase during carcinogenesis. Of the latter two enzymes, aldehyde reductase increases more markedly in a progressive fashion during the months of development of nodules and hepatoma. The increase of enzymes able to metabolize 4-hydroxynonenal, as well as other aldehydes, is certainly important in protecting tumour cells against cytotoxic effect of aldehydes.
The intravenous injection of Ehrlich tumour cells (TC) into Swiss mice, or BP8-fibrosarcoma cells into C3H mice, caused no intra-organ dissemination of the tumour but resulted in increasing resistance of animals to these two tumours. The percentage of mice protected against a regularly lethal dose of TC given intraperitoneally (i.p.) increased with the dose and the number of immunizing injections to the i.p. challenge. However, after high or repeated doses a cancerous nodule sometimes developed at the site of intravenous injections (penis vein), which caused death of the animal, not by extension of the tumour but by urethral occlusion. Moderate heating (46, 49.5 or 52 degrees C) of the TC did not impair their immunogenicity but prevented their multiplication in normal mice. It was thus possible, by intradermal injections of heated TC, to protect mice against a dose of intact TC. The efficiency of prophylaxis depended on the temperature to which the cells were exposed (optimal temperature depending on the type of tumour), on the number of injections and on the medium in which the cells were suspended. When Freund's complete adjuvant was used, all mice were protected against tumour ascites following challenge.
During endochondral ossification (EO), cartilage is replaced by bone. Chondrocytes of growth plate undergo proliferation, maturation, hypertrophy, matrix vesicle (MV) biogenesis and programmed cell death (PCD, apoptosis). The in vitro system presented here provides a potential experimental model for studying in vitro differentiation and MV biogenesis in chondrocyte cultures. Chondrocytes were obtained from collagenase-digested tibial and femoral growth plate cartilage of 7-week-old rachitic rats. The isolated chondrocytes were plated as monolayers at a density of 0.5 x 10(6) cells per 35-mm plate and grown for 17 days in BGJ(b) medium supplemented with 10% fetal bovine serum, 50 microg/ml ascorbic acid. Light microscopy revealed Sirius red-positive, apparent bone matrix in layers at the surfaces of cartilaginous nodules that developed in the cultures. The central matrix was largely alcian blue staining thus resembling cartilage matrix. Electron microscopy revealed superficial areas of bone like matrix with large banded collagen fibrils, consistent with type I collagen. Most of the central matrix was cartilaginous, with small fibrils, randomly arranged consistent with type II collagen. The presence of peripheral type I and central type II and type X collagen was confirmed by immunohistochemical staining. Immunohistochemistry with anti-Bone morphogenetic proteins 2, 4 and 6 showed that BMP expression is associated with maturing hypertrophic central chondrocytes, many of which were TUNEL positive and undergoing cell death with plasma membrane breaks, hydropic swelling and cell fragmentation. During early mineralization, small radial clusters of hydroxyapatite-like mineral were associated with matrix vesicles. Collagenase digestion-released MVs from the cultures showed a high specific activity for alkaline phosphatase and demonstrated a pattern of AMP-stimulated nonradioactive (40)Calcium deposition comparable to that observed with native MVs. These studies confirm that primary cultures of rat growth plate chondrocytes are a reasonable in vitro model of growth plate histotype, MV biogenesis and programmed cell death.
AIM: To study in vivo whether pancreatic cancer tumour growth and metastasis can be modified by a gene construct with HSV-TK suicide gene and IL2 co-expression. METHODS: Seventy-eight female SCID mice were i.p. inoculated with retrovirally transduced or control MIA PaCa 2, CAPAN-1 and PANC-1 cell lines. The animals were then randomly selected for saline or ganciclovir (GCV) treatment from the second week, for a total of two weeks. RESULTS: Most inoculated mice developed tumour nodules and spleen metastases. The liver was colonized by control CAPAN-1 and MIA PaCa 2, but not by PANC-1. Tumours in transduced MIA PaCa 2 cell injected mice were smaller, and in transduced CAPAN-1 injected mice larger, than in control-inoculated mice. There were increased pancreatic and decreased spleen metastases from transduced CAPAN-1, and diminished liver involvement from transduced MIA PaCa 2. No differences were found between mice inoculated with transduced and control PANC-1 cell lines. GCV treatment had no effect on tumour's size or metastases. CONCLUSIONS: The HSV-TK suicide gene does not confer GCV sensitivity to pancreatic cancer in this in vivo model. Different pancreatic cancer cell lines cause different growth and metastasis patterns after inoculation in SCID mice, possibly because of variations in their inherent characteristics. The different effects of our vector on cell growth and metastasis may be attributable to the effects of the immunostimulatory cytokine IL2.
Susceptibility to infection with Leishmania amazonensis promastigotes was examined in six B10 congenic mouse strains, including C57BL/10J (H2b), B10.BR (H2k), B10.M (H2f), B10.S (H2s), B10.RIII (H2r), and B10.D2 (H2d). All strains of mice developed skin nodules with punch-out ulcers by 8 weeks post-infection, but B10.M and B10.S mice showed resolution of cutaneous leishmaniasis lesions by 16 weeks post-infection. In addition, the skin lesions were much larger in BALB congenic mice than in B10 and C3H mice, even though these mice share the same H2 haplotypes. These results suggest that H2 complex controls the growth of L. amazonensis in cutaneous lesions, and that non-H2 genes inherited by BALB congenic mice have a more potent role than the H2 complex in lesion progression.
Mine drainage waters vary considerably in the range and concentration of heavy metals they contain. Besides iron, manganese is frequently present at elevated concentrations in waters draining both coal and metal mines. Passive treatment systems (aerobic wetlands and compost bioreactors) are designed to remove iron by biologically induced oxidation/precipitation. Manganese, however, is problematic as it does not readily form sulfidic minerals and requires elevated pH (>8) for abiotic oxidation of Mn (II) to insoluble Mn (IV). As a result, manganese removal in passive remediation systems is often less effective than removal of iron. This was found to be the case at the pilot passive treatment plant (PPTP) constructed to treat water draining the former Wheal Jane tin mine in Cornwall, UK, where effective removal of manganese occurred only in one of the three rock filter components of the composite systems over a 1-year period of monitoring. Water in the two rock filter systems where manganese removal was relatively poor was generally <pH 5, whereas it was significantly higher ( approximately pH 7) in the third (effective) system. These differences in water chemistry and manganese removal were due to variable performances in the compost bioreactors that feed the rock filter units in the composite passive systems at Wheal Jane. An alternative approach for removing soluble manganese from mine waters, using fixed bed bioreactors, was developed. Ferromanganese nodules (about 2 cm diameter), collected from an abandoned mine adit in north Wales, were used to inoculate the bioreactors (working volume ca. 700 ml). Following colonization by manganese-oxidizing microbes, the aerated bioreactor catalysed the removal of soluble manganese, via oxidation of Mn (II) and precipitation of the resultant Mn (IV) in the bioreactor, in synthetic media and mine water from the Wheal Jane PPTP. Such an approach has potential application for removing soluble Mn from mine streams and other Mn-contaminated water courses.
The incidence of an adenoid cystic carcinoma on major salivary glands is low, constituting only about 10% to 15% of all parotid malignancies. Cases of delayed metastasis have been reported, but reports of specific renal involvement have not been extensively found. We present the case of a 21-year-old woman with a left renal metastasis from an adenoid cystic carcinoma of the parotid gland that had been surgically treated 7 years previously. The patient underwent successful left radical nephrectomy. During follow-up, the patient developed pulmonary nodules that were metastatic adenoid cystic carcinoma and were surgically excised. At last follow-up, the patient was doing well with no evidence of disease.
The present study reports on the frequency of liver tumors observed in a gene therapy study with AAV vectors in male mice of the B6C3F1 hybrid background, which are known to have a high frequency of spontaneous liver tumors. Male mice with mutations in their Otc gene and their wild-type siblings received AAV vectors expressing either the murine Otc or the LacZ gene. Untreated control animals were included in the study. All experimental groups, including wild-type and OTC-deficient animals not treated with vector, developed liver nodules, which in some cases were due to hepatocellular carcinoma. Vector DNA was lower in tumors than in adjacent normal liver. A statistical analysis of the data did not show an association between treatment with Otc vectors and formation of tumors in OTC-deficient mice. However, mice treated with LacZ vectors showed increased risks of tumor formation and hepatocellular carcinoma relative to untreated animals or animals that had received vectors with Otc as the transgene. It appears that AAV vectors alone do not contribute to the formation of tumors in these strains of mice although the expression of LacZ alone or in combination with vector may be problematic.
Polypeptide growth factors stimulate mammalian cell proliferation by binding to specific cell surface receptors. This interaction triggers numerous biochemical responses including the activation of protein phosphorylation cascades and the enhanced expression of specific genes. We have identified several fibroblast growth factor (FGF)-inducible genes in murine NIH 3T3 cells and recently reported that one of them, the FGF-inducible 14 (Fn14) immediate-early response gene, is predicted to encode a novel, cell surface-localized type Ia transmembrane protein. Here, we report that the human Fn14 homolog is located on chromosome 16p13.3 and encodes a 129-amino acid protein with approximately 82% sequence identity to the murine protein. The human Fn14 gene, like the murine Fn14 gene, is expressed at elevated levels after FGF, calf serum or phorbol ester treatment of fibroblasts in vitro and is expressed at relatively high levels in heart and kidney in vivo. We also report that the human Fn14 gene is expressed at relatively low levels in normal liver tissue but at high levels in liver cancer cell lines and in hepatocellular carcinoma specimens. Furthermore, the murine Fn14 gene is rapidly induced during liver regeneration in vivo and is expressed at high levels in the hepatocellular carcinoma nodules that develop in the c-myc/transforming growth factor-alpha-driven and the hepatitis B virus X protein-driven transgenic mouse models of hepatocarcinogenesis. These results indicate that Fn14 may play a role in hepatocyte growth control and liver neoplasia.
Two Rac GTPase cDNAs, LjRac1 and LjRac2, were identified in the legume Lotus japonicus. Two-hybrid screening with dominant-constitutive mutations in the two Rac GTPases target three plant cDNAs, LjRacGAP1, LjRacGAP2 and LjRacGAP3, that encode putative GTPase activating proteins of Rho-GTPase subfamily members. Employing Rac antiserum, purified recombinant LjRac GTPases and recombinant LjRacGAP1, for ligand overlay assays, in vitro GAP affinity assays and GTPase activation, we confirmed that eukaryote Rac/RacGAP interplay is conserved in plants. In this investigation we have developed some tools that can be used to characterize the role of enhanced LjRac2 expression in developing root nodules.
A transplantable tumour (HS-J) was established from a spontaneous histiocytic sarcoma found in a 24-month-old male F344 rat. Serial transplantations (seven generations) were made in syngeneic male and female rats by means of intraperitoneal or subcutaneous implants, with a 100% take rate. Rats given HS-J implants developed large nodules locally, with metastasis to distant organs. HS-J tumours consisted mainly of round to oval cells with abundant cytoplasm, arranged in a compact sheet. Enzyme- and immuno-histochemical examination showed that neoplastic cells reacted with ED1 (rat monocyte/macrophage-specific antibody), lysozyme, alpha 1-antitrypsin and lysosomal enzymes (acid phosphatase and non-specific esterase), indicating derivation from cells of the monocyte/macrophage lineage. The majority of neoplastic cells were negative for ED2 (rat tissue macrophage-specific antibody). Abnormal accumulations of hyaline droplets in the proximal renal tubular epithelial cells were seen in HS-J-bearing rats. The droplets were faintly immunopositive for lysozyme, but negative for alpha-2u globulin and albumin. It was considered that excessive production of the protein by tumour cells might lead to subsequent overload in renal tubules. HS-J may prove beneficial for studying the biological behaviour of monocyte/macrophage-derived tumours in the rat.
Central venous catheters have proven to be an important aid for the care of pediatric patients with malignancies receiving chemotherapy. A rare complication of such catheters is pulmonary septic emboli. This report describes a 15-year-old white girl with rhabdomyosarcoma who developed pulmonary nodules while on chemotherapy. These lesions appeared to be metastatic rhabdomyosarcoma. However, an excisional biopsy showed the lesions to be septic emboli. The patient was placed on antibiotic therapy and responded well. She was able to continue with her "front-line" therapy because the nodules were confirmed not to be metastatic disease.
PURPOSE: Black pigmentation of the thyroid gland is a rare side effect of minocycline. METHODS: Only 26 cases, in addition to the 2 we present, have been reported in the literature. Eleven cases of thyroid carcinoma associated with black thyroid syndrome have been reported. CONCLUSIONS: The incidence of papillary cancer may be increased in thyroid glands stained by the minocycline pigment, which warrants an increased index of suspicion in patients who develop thyroid nodules and have previously been treated with minocycline.
Following a RT-PCR strategy based on the design of degenerate oligonucleotides resembling conserved domains of asparagine synthetase (AS; EC 6.3.5.4), we isolated a 2 kb cDNA clone (PVAS2) from root tissue of the common bean (Phaseolus vulgaris). PVAS2 encodes a protein of 584 amino acids with a predicted relative molecular mass of 65810 Da, an isoelectric point of 6.4, and a net charge of -7.2 at pH 7.0. The amino acid sequence of the protein encoded by PVAS2 is very similar to that encoded by the soybean SAS2 asparagine synthetase gene. The amino-terminal residues of the predicted PVAS2 protein are identical to the amino acids that constitute the glutamine-binding (GAT) domain of AS from other plant species, which suggests that the PVAS2 cDNA encodes a type II glutamine-dependent form of asparagine synthetase. Southern blot analysis indicates that the common bean AS is part of a small family composed of at least two genes. Expression analysis by Northern blot revealed that the PVAS2 transcript accumulates to a high level in roots and, to a lesser extent, in nodules and developing pods. Accumulation of the PVAS2 transcript in the root seems to be negatively regulated by light and sucrose, and positively regulated by nitrate.