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PubMed2003

Acral arteriovenous tumor developed within a nevus flammeus in a patient with Sturge-Weber syndrome.

The Sturge-Weber syndrome consists of a large facial nevus flammeus in the distribution of the ophthalmologic division of the trigeminal nerve accompanied by ipsilateral leptomeningeal angiomatosis. Usually, when angiomatous nodules develop in a nevus flammeus of a patient with Sturge-Weber syndrome they are pyogenic granulomas. We describe an acral arteriovenous tumor developed within the nevus flammeus of a patient with Sturge-Weber syndrome. To our knowledge, acral arteriovenous tumor has not been previously described in the cutaneous vascular malformation of patients with Sturge-Weber syndrome. The development of acral arteriovenous tumor within the vascular malformation of a nevus flammeus in this patient with Sturge-Weber syndrome probably results from a vascular proliferation secondary to underlying arteriovenous shunts.

Facial Neoplasms↗
PubMed2004

Complexity of phenotypes and symbiotic behaviour of Rhizobium leguminosarum biovar trifolii exopolysaccharide mutants.

Rhizobium leguminosarum biovar trifolii strain TA1 polysaccharide synthesis (pss) mutants in the pssD, pssP, pssT and pssO genes and altered in exopolysaccharide (EPS) synthesis were investigated. EPS-deficient mutants were also changed in lipopolysaccharide structure. All mutants exhibited varied sensitivities to detergents, ethanol and antibiotics, thus indicating changes in bacterial membrane integrity. Using pss mutants marked with the gusA gene, EPS-deficient mutants were found to have abnormalities in nodule development and to provoke severe plant defence reactions. The pss mutants that produced altered quantities of EPS with a changed degree of polymerisation generally occupied the younger developmental zones of the nodules and elicited moderate plant defence reactions.

Drug Resistance, Bacterial↗
PubMed1993

[Studies on initiating activity of secondary bile acids for rat hepatocarcinogenesis].

The initiating potential of the secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA), was investigated using the development of preneoplastic lesions in the rat liver as a marker. In a short-term assay in which DCA and LCA were given in the diet for 3 weeks in conjunction with partial hepatectomy midway followed by the selection regimen, DCA dose-dependently induced gamma-glutamyltranspeptidase (gamma-GTP)-positive foci, but the results for LCA were less unequivocal and no dose-dependency was evident. In another experiment, I extended the period of observation and examined whether the gamma-GTP-positive foci thus induced by the secondary bile acids can develop into hepatic tumors after a latent period of 52 weeks with or without the administration of phenobarbital (PB), a promoter of experimental hepatocarcinogenesis. Whereas significantly high numbers of hyperplastic liver nodules developed in the DCA-treated rats irrespective of PB promotion, no such increase was evident in the LCA-treated rats. In contrast, both DCA and LCA treatments enhanced the development of glutathione S-transferase placental form (GST-P)-positive foci with or without subsequent PB promotion. The present data indicate that a short period of administration of DCA and LCA in the initiation stage in conjunction with partial hepatectomy results in enhanced development of preneoplastic liver lesions under selection pressure conditions with or without subsequent PB promotion. This suggests that these secondary bile acids possess possible initiating activity for rat hepatocarcinogenesis.

Animals↗
PubMed1993

Regulation of syrM and nodD3 in Rhizobium meliloti.

The early steps of symbiotic nodule formation by Rhizobium on plants require coordinate expression of several nod gene operons, which is accomplished by the activating protein NodD. Three different NodD proteins are encoded by Sym plasmid genes in Rhizobium meliloti, the alfalfa symbiont. NodD1 and NodD2 activate nod operons when Rhizobium is exposed to host plant inducers. The third, NodD3, is an inducer-independent activator of nod operons. We previously observed that nodD3 carried on a multicopy plasmid required another closely linked gene, syrM, for constitutive nod operon expression. Here, we show that syrM activates expression of the nodD3 gene, and that nodD3 activates expression of syrM. The two genes constitute a self-amplifying positive regulatory circuit in both cultured Rhizobium and cells within the symbiotic nodule. We find little effect of plant inducers on the circuit or on expression of nodD3 carried on pSyma. This regulatory circuit may be important for regulation of nod genes within the developing nodule.

Bacterial Proteins↗
PubMed1986

Palindromic rheumatism with rheumatoid nodules: a case report with ultrastructural studies.

Rheumatoid nodules developed on the finger tips of a patient with palindromic rheumatism. The patient had no bone cysts or erosions and had no rheumatoid factor. A light microscopic and ultrastructural study of a nodule showed a necrotic centre with fibrin, collagen, and granular material surrounded by large histiocytes, fibrocytes, lymphocytes, and vessels with adjacent mast cells as has been seen with nodules in classical rheumatoid arthritis (RA). We describe the first immunoperoxidase studies on a rheumatoid nodule and have identified reaction products for immunoglobulins and C3 in perivascular and endothelial cell vacuoles and in the necrotic centre.

Humans↗
PubMed1998

The Lotus japonicus LjNOD70 nodulin gene encodes a protein with similarities to transporters.

A novel nodule-specific gene, LjNOD70, associated with late stages in Lotus japonicus nodule development and/or functioning was characterized. The LjNOD70 gene is a member of a small family of closely related L. japonicus genes. Two major mRNA species corresponding to the LjNOD70 gene were identified in nodules and shown to be the result of a mechanism resembling alternative splicing. The longer, presumably unspliced, mRNA species was shown to contain a single open reading frame (ORF), encoding a polytopic hydrophobic protein, LjN70, with a predicted molecular mass of 70 kDa. The second, presumably spliced, mRNA species was shown to be less abundant in nodules. The absence of the presumptive 'intron' was found to divide the reading frame into an upstream and a downstream ORF encoding the partial N- and C-terminal regions of the LjN70 protein, respectively. The predicted amino acid sequence of nodulin LjN70 revealed structural features characteristic of transport proteins, and was found to share similarity with the oxalate/formate exchange protein of Oxalobacter formigenes. Therefore, we postulate that the L. japonicus LjNOD70 gene family encodes nodule-specific transport proteins, which may have evolved as a result of exon-intron shuffling.

Alternative Splicing↗
PubMed2002

Dupuytren's disease: physiologic changes in nodule and cord fibroblasts through aging in vitro.

The pathogenesis of the fibrotic disease Dupuytren's contracture remains unclear. The disease process includes two structurally distinct fibrotic elements, the nodule and the cord. It has been proposed that as the disease progresses, nodules develop into cords. To corroborate that hypothesis, the authors took advantage of cultured fibroblast differences found between gap junction intercellular communication and fibroblast-populated collagen lattice contraction. Paired fibroblast cell lines of nodules and cords derived from four patients with Dupuytren's disease were maintained in culture for at least eight passages. The presence of gap junction intercellular communication in nodule- and cord-derived fibroblasts was documented and reported as a coupling index. The contraction of free-floating nodule- or cord-derived collagen lattices was also documented and reported. Early passage (passage 4) cord-derived fibroblasts showed a significant increase in coupling index compared with passage 4 nodule-derived fibroblasts (4.0 +/- 0.4 versus 2.5 +/- 0.3, respectively), where p < or = 0.01. However, late passage (passage 8) nodule- and cord-derived fibroblasts were equivalent in their coupling index (4.1 +/- 0.4 versus 4.4 +/- 0.4, respectively). Early passage nodule-derived fibroblast-populated collagen lattices contracted by 64 percent, whereas late passage nodule-derived lattices showed less contraction, at only 40 percent. Early and late passage cord-derived lattices contracted 46 and 37 percent, respectively. All nodule- and cord-derived cell lines were statistically equivalent at lattice contraction by passage 8. These in vitro studies support the hypothesis that fibroblasts derived from Dupuytren's contracture nodules change their phenotype after undergoing repeated cell passage, acquiring a cord-like fibroblast phenotype. Dupuytren's nodules represent the early, active form of fibrosis in which cells are more proliferative, better at fibroblast-populated collagen lattice contraction, and display less gap junction intercellular communication. The speculation is that alterations in gap junction intercellular communication may be involved in the progression of Dupuytren's nodules to cords as the disease progresses.

Cell Communication↗
PubMed1988

Identification of cytoplasmic nodule-associated forms of malate dehydrogenase involved in the symbiosis between Rhizobium leguminosarum and Pisum sativum.

The malate dehydrogenase activity (EC 1.1.1.37), present in the cytoplasm of Pisum sativum root nodules, can be separated by ion-exchange chromatography into four different fractions. Malate dehydrogenase activity present in the cytoplasm of roots elutes mainly as a single peak. During nodule development an increase in malate dehydrogenase activity per gram of material was observed. This increase occurred concomitantly with the increase in nitrogenase activity. The kinetic properties of the separated malate dehydrogenases of root nodule cytoplasm and root cytoplasm were studied. The Km values for malate (2.6 mM), NAD+ (27 microM), oxaloacetate (18 microM) and NADH (13 microM) of the dominant form of the root nodule cytoplasm are much lower than those of the dominant malate dehydrogenase root form (64 mM, 4.4 mM, 89 microM and 70 microM respectively). Binding of malate by the enzyme-NADH complex from root nodules results in an abortive complex, thereby blocking the further reduction of oxaloacetate by NADH. The dominant root malate dehydrogenase does not form the abortive complex. From the kinetic data it is concluded, first, that the root nodule forms of the enzyme are capable of catalysing at a high rate the reduction of oxaloacetate, to meet the demands for malate governed by the bacteroid and the infected plant cell. The second conclusion, drawn from the kinetic data, is that under physiological conditions the conversion of oxaloacetate can be controlled just by the malate concentration. Consequently the major root nodule forms of malate dehydrogenase are able to allow a high flux of malate production from oxaloacetate but also to establish a sufficient oxaloacetate concentration necessary for the assimilation and transport of fixed nitrogen.

Biological Transport↗
PubMed1995

[Idiopathic myelofibrosis with extramedullary hematopoiesis foci in the skin and testicles. Report of a case].

Idiopathic myelofibrosis (IMF) is a clonal chronic myeloproliferative syndrome characterized by the proliferation of the three haemopoietic series and the marrow connective tissue and by the development of extramedullary haemopoiesis in the liver, spleen and lymph nodes. Cutaneous extramedullary haemopoiesis is an uncommon event and we could not find any reported cases of testicular involvement in this disease. We report the case of a 28 year-old male with diagnosis of idiopathic myelofibrosis in November 1988. During the course of the disease, three years later, he developed a tumor on his right testis. Histologic examination showed extramedullary haemopoiesis with cells of the myeloid, erythroid and megakaryocyte series, in the interstice. Eight months later, numerous red-purple papules and nodules developed on the patients's trunk. The biopsy of a skin lesion revealed an infiltration of the dermis by myeloid, erythroid cells and few megakaryocytes. The patient's clinical condition worsened, and he died in February 1993 following progressive deterioration of the general condition. We describe a case of IFM with extramedullary hemopoiesis involving the skin and the testis pointing out the rarity of these localization.

Adult↗
PubMed1981

Organ culture passage enhances the oncogenicity of carcinogen-induced hyperplastic mammary nodules.

The purpose of this study was to determine whether culturing hyperplastic mammary nodules in hormone-free medium would enhance their oncogenicity following subsequent transplantation into mammary fat pads. The underlying hypothesis is that the proliferation of transformed cells within the nodules is inhibited by hormone-dependent normal cells also present in the nodules. Accordingly, both primary hyperplastic nodules and tissues from a hyperplastic outgrowth of a primary nodule were maintained as organ cultures for varying periods in hormone-free Medium 199. The results show that whereas noncultured nodules developed mammary tumors at an incidence of only 15%, those passaged in organ culture gave rise to mammary tumors at an incidence of 40 to 43%. This threefold enhancement in the oncogenicity of mammary nodules is interpreted to be due, at least in part, to a reduction in the normal mammary cell content of nodules. Consistent with this interpretation is the observation that cultured nodules gave rise to mammary outgrowths that were predominantly hyperplastic, whereas noncultured nodules generated outgrowths with varying proportions of hyperplastic and normal ductal mammary tissue.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Cutaneous metastasis of CNS chordoma.

A rare case of cutaneous skin metastasis from an intracranial chordoma is presented. A large nodule developed in the left thigh of a 22-year-old woman who had been previously diagnosed to have a chordoma at the base of her skull. Sections from the biopsied specimens of the nodule showed proliferations of physaliphorous cells and stellate cells in cords and in nests in a myxoid stroma. Immunohistochemically, neoplastic cells were stained positively with antibodies to S-100 protein and cytokeratin. The results of the histopathological and immunohistochemical studies of the nodule were interpreted as pointing to a diagnosis of metastatic chordoma based on their similarity to the results of studies of the primary neoplasm in the cranial region. Based on the number of cases of skin metastasis from chordoma reported in the literature, skin should be kept in mind as one of the target organs, although such metastases are still rare.

Adult↗
PubMed1986

[Gluteal granuloma in an infant].

This report deals with a 5-month-old infant who at the age of 2 months was treated with topical fluorinated steroids for dermatitis in the diaper area. The treatment was continued for about 2 months. Some weeks later, multiple oval and round dark brown nodules developed in the inguinogenital areas. Histologic examination of these lesions revealed intense granulomatous infiltration in the upper dermis that consisted of lymphocytes, neutrophilic and eosinophilic granulocytes, and histiocytes. After steroid therapy was discontinued, the nodules slowly disappeared.

Buttocks↗
PubMed1997

The entry of ivermectin and suramin into Onchocerca ochengi nodules.

No currently available drug, which is safe for mass treatment, effectively kills adults of Onchocerca volvulus, the causal agent of onchocerciasis in humans, or of O. ochengi, a cattle parasite used as a model of O. volvulus. Since adults of both of these filarial nematodes are found in well developed nodules, the lack of efficacy of these drugs may be a result of their poor penetration into the nodules. To check if this was the problem, the distributions of the microfilaricide, ivermectin, and the partial macrofilaricide, suramin, in plasma, skin, nodule capsules and nodule contents were determined in cattle naturally infected with O. ochengi in Cameroon. The cattle were treated with either a single, subcutaneous injection of 500 micrograms ivermectin/kg, or with intravenous injections of [14C]-labelled suramin, each of 10 mg/kg, given one a day for 6 days. Concentrations of ivermectin and suramin in various tissues were then assayed by high-pressure liquid chromatography and scintillation counting, respectively. On day 7 post-treatment (pt), suramin concentrations were consistently highest in the nodule, contents and capsule wall (11.0 and 8.9 nCi/g, respectively) and significantly less in skin and plasma (1.2 and 1.4 nCi/g, respectively; P < 0.05). The distribution of ivermectin on day 7 pt was similar, with the highest concentrations in the capsule wall, nodule contents and plasma (58.4 ng/g, 43 ng/g and 48.6 ng/ml, respectively; P > 0.05) and the concentration in the skin (6.4 ng/g) significantly lower than those in the capsule or plasma (P < 0.05). High intra-nodular concentrations of both drugs were maintained for 5-7 days at least and those of ivermectin would be expected to kill nematodes other than filariae. It is apparent that failure of ivermectin and suramin to kill adult Onchocerca spp. is not because the drugs penetrate nodules inadequately.

Animals↗
PubMed2005

3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone [MX] shows initiating and promoting activities in a two-stage BALB/c 3T3 cell transformation assay.

A transformation assay using BALB/c 3T3 cells was conducted on 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) to assess initiation and promotion activities of MX carcinogenesis. Statistically significant positive responses were obtained compared with the corresponding solvent controls in both the initiation assay post-treated with 12-O-tetradecanoylphorbol 13-acetate (TPA) and the promotion assay pretreated with 3-methylcholanthrene (MCA). Both TPA and MX inhibited metabolic cooperation in an assay using co-culture of V79 6-thioguanine (6-TG) sensitive and insensitive cells. However, cells isolated from transformed foci in the initiation assay did not induce any nodules after inoculation to BALB/c mice, the strain of mouse from which the transformation assay cells were derived. Although the study was carried out for 2-3 weeks, this might have been too short to develop nodules under the conditions of this experiment. This in vitro cell transformation study with MX adds supportive information to studies showing MX carcinogenicity and tumour promoter activity, and adds mechanistic understanding of the action of MX.

Animals↗
PubMed2006

The Rhizobium leguminosarum biovar trifolii ANU794 induces novel developmental responses on the subterranean clover cultivar Woogenellup.

The clover-nodulating Rhizobium leguminosarum bv. trifolii ANU794 initiates normal root-nodule development with abnormally low efficiency on the Trifolium subterraneum cv. Woogenellup. The cellular and developmental responses of Woogenellup roots to the site- and dose-defined inoculation of green fluorescent protein (gfp)-labeled cells of ANU843 (nodulation proficient) and ANU794 was investigated using light, fluorescence, and confocal microscopy. Strain ANU794-gfp induced three primordia types and four developmental responses at the inoculation site: true or aberrant nodules (on 5 and 25% of plants, respectively), hybrid structures (20% of plants), or lateral roots (50% of plants). The novel hybrid structures possessed nodule and lateral root-like features and unusual vascular patterning. Strain ANU794-gfp induces lateral root formation by stimulating pericycle cell divisions at all nearby protoxylem poles. Only true nodules induced by ANU794-gfp contained intracellular bacteria. In contrast, strain ANU843-gfp induced nodules only and lateral root formation was suppressed at spot inoculation sites. Primordium types were distinguishable by the emission spectrum characteristics of phenolic UV-absorbing and fluorescent compounds that accumulate in primordium cells. Hybrid primordia contained (at least) two fluorescent cell populations, suggesting that they are chimeric. The results suggest that ANU794 may produce both nodule- and lateral root-generating signals simultaneously.

Chromatography, High Pressure Liquid↗
PubMed2005

Multiple dermatofibromas associated with lupus profundus.

We report a 58-year-old Afro-Caribbean woman who presented with more than 20 dermatofibromas on the body particularly on the back, arms and legs. These developed spontaneously over the course of 5 years. She also had a long-standing 5 x 2-cm area of lipoatrophy on the right upper arm and a 2-year history of several inflammatory subcutaneous nodules developing on the upper chest and left breast. These were confirmed histologically as lupus profundus. Apart from a mild arthritis, she had no other markers for systemic lupus erythematosus and was systemically well. Multiple dermatofibromas are rare. There are around 30 reports of multiple dermatofibromas associated with systemic diseases. More than half of these cases were associated with systemic lupus erythematosus, with or without systemic steroid therapy and about one-third were associated with HIV infection. Although the mechanism is unknown, it appears that multiple dermatofibromas are associated with autoimmune diseases or altered immune states. This is the first case of multiple dermatofibromas associated with lupus profundus. The knowledge of such associations may contribute to the understanding of the pathogenesis of dermatofibromas, which is as yet unknown.

Autoimmune Diseases↗
PubMed1987

Influence of ethanol on development of hyperplastic nodules in alcoholic men with micronodular cirrhosis.

The type of cirrhosis was blindly evaluated in follow-up liver biopsies performed on 106 alcoholic men with micronodular cirrhosis. The median time interval from entry to follow-up liver biopsy was 31 mo (range, 3-44 mo). Patients were stratified into four groups according to their maximal registered ethanol consumption during follow-up. Thirty-six patients (34%) abstained from ethanol, 40 patients (38%) consumed a small amount of ethanol (less than 50 g/day), 19 patients (18%) consumed a moderate amount of ethanol (51-100 g/day), and 11 patients (10%) consumed an excessive amount of ethanol (greater than 100 g/day) during follow-up. Follow-up liver biopsy specimens demonstrated micronodular cirrhosis in 54 patients (51%), micronodular cirrhosis with development of hyperplastic nodules in 47 patients (44%), and nonclassifiable macronodular cirrhosis in 4 patients (4%); 1 patient showed portal fibrosis. The cumulative prevalence of patients developing hyperplastic nodules increased significantly (p = 0.014 for trend) with decreasing ethanol consumption, the prevalence being 57% in abstainers, 58% in those who consumed a small amount of ethanol, 32% in those who consumed a moderate amount, and 18% in those who consumed an excessive amount. In conclusion, alcoholic men with micronodular cirrhosis develop hyperplastic nodules during follow-up, the rate and prevalence of which is significantly related to the amount of ethanol consumed during follow-up. Ethanol consumption may inhibit hepatocellular proliferation in alcoholic men with micronodular cirrhosis.

Adult↗
PubMed2005

Renal oncocytosis.

Renal oncocytosis is a rare disorder in which numerous oncocytic nodules develop in the kidney. An additional case is reported here. The patient was a 51-year-old woman who had received hemodialysis for 27 years. Nineteen years previously she had developed a tumorous lesion in the right kidney, which had been diagnosed as oncocytoma with laparotomic biopsy. Recently the kidney was removed because of enlargement of the tumor. The renal parenchyma was entirely replaced with numerous brownish nodules. Histologically, the nodules were composed of nests of uniform oncocytic cells. Ultrastructurally, the oncocytic cells contained numerous mitochondria. Immunohistochemical features of the nodules were identical to those of sporadic oncocytomas, that is, immunophenotypes similar to the distal nephron and reactivity with antimitochondrial antigen. Based on these findings, the lesion was diagnosed as renal oncocytosis. It was not possible to determine whether the larger nodules should be diagnosed as oncocytoma or a part of oncocytosis. Additionally, the germ line mutation of the Birt-Hogg-Dubé (BHD) syndrome gene was examined using the genomic DNA obtained from the peripheral lymphocytes, which failed to show any gene alteration. Despite the rare occurrence pathologists and urologists should be aware of renal oncocytosis, as a precursor lesion of renal oncocytoma and chromophobe renal cell carcinoma.

Adenoma, Oxyphilic↗