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PubMed2006

Congenital melanocytic nevi frequently harbor NRAS mutations but no BRAF mutations.

Most melanocytic nevi develop on sun-exposed skin during childhood and adolescence and commonly harbor BRAF mutations or, less frequently, NRAS mutations. A small subset of nevi is present at birth, and therefore must develop independently of UV light. To assess whether these nevi have a different mutation spectrum than those that develop on sun-exposed skin, we determined the BRAF and NRAS mutation frequencies in 32 truly congenital nevi. We found no BRAF mutations, but 81% (26/32) harbored mutations in NRAS. Consistently, seven of 10 (70%) proliferating nodules that developed early in life in congenital nevi showed mutations in NRAS. A separate set of nevi that displayed histological features frequently found in nevi present at birth ("congenital pattern nevi") but lacked a definitive history of presence at birth showed an inverse mutation pattern with common BRAF mutations (20/28 or 71%) and less frequent NRAS mutations (7/28 or 25%). Thus, nevi that develop in utero are genetically distinct from those that develop later, and histopathologic criteria alone are unable to reliably distinguish the two groups. The results are consistent with the finding in melanoma that BRAF mutations are uncommon in neoplasms that develop in the absence of sun-exposure.

Adolescent↗
PubMed2003

Distinct patterns of symbiosis-related gene expression in actinorhizal nodules from different plant families.

Phylogenetic analyses suggest that, among the members of the Eurosid I clade, nitrogen-fixing root nodule symbioses developed multiple times independently, four times with rhizobia and four times with the genus Frankia. In order to understand the degree of similarity between symbiotic systems of different phylogenetic subgroups, gene expression patterns were analyzed in root nodules of Datisca glomerata and compared with those in nodules of another actinorhizal plant, Alnus glutinosa, and with the expression patterns of homologous genes in legumes. In parallel, the phylogeny of actinorhizal plants was examined more closely. The results suggest that, although relationships between major groups are difficult to resolve using molecular phylogenetic analysis, the comparison of gene expression patterns can be used to inform evolutionary relationships. In this case, stronger similarities were found between legumes and intracellularly infected actinorhizal plants (Alnus) than between actinorhizal plants of two different phylogenetic subgroups (Alnus/Datisca).

Amino Acid Sequence↗
PubMed1993

Influence of orotic acid on multistage hepatocarcinogenesis in the rat: resistance of hepatocytes from nodules to the mitoinhibitory effects of orotic acid.

This study was designed to determine whether hepatocytes from hepatic nodules are resistant to the mitoinhibitory effects of orotic acid. Hepatic nodules were initiated in Fischer 344 male rats with 1,2-dimethylhydrazine.2HCl (100 mg/kg ip) given 16 hr after two thirds partial hepatectomy and promoted by feeding a diet containing 1% orotic acid. Eight to 9 months later, when persistent nodules had developed, the rats were taken off the orotic acid diet and maintained on a semisynthetic basal diet for 2 to 5 weeks. The effect of orotic acid on the DNA synthesis in the hepatocytes isolated from hepatic nodules and from the surrounding nonnodular liver and from the age- and sex-matched control rats was studied. The results indicated that a dose of orotic acid (120 microM) that almost completely inhibited the transforming growth factor-alpha-induced DNA synthesis in hepatocytes from nonnodular surrounding liver and from age- and and sex-matched control liver could not inhibit the DNA synthesis in hepatocytes from hepatic nodules. These results are consistent with the postulate that orotic acid may promote liver carcinogenesis by a differential mitoinhibition of normal hepatocytes while permitting the initiated hepatocytes to respond to growth stimuli and form hepatic nodules. However, it needs to be determined whether differential mitoinhibition of normal hepatocytes is the mechanism by which orotic acid promotes liver carcinogenesis.

1,2-Dimethylhydrazine↗
PubMed1995

[Use of CT-guided metal wires in pre-thoracoscopic localization of peripheral pulmonary nodules].

The recent developments in thoracic surgery have broadened the application spectrum of thoracoscopy. Video-assisted thoracoscopic lung resection is now available both to diagnose and to treat peripheral pulmonary nodules. A major factor limiting the success of thoracoscopic lung resection is the difficult localization of the pulmonary nodule. When lesions are very small and deep inside the lung, their preoperative detection may be difficult. This study was aimed at investigating the effectiveness of hookwires for CT-guided localization of peripheral pulmonary lesions requiring thoracoscopic resection. In 12 patients 12 nodules, previously detected with chest radiography, were localized with hookwires under CT guidance. Ten of 12 patients underwent thoracoscopic resection for diagnostic purposes, while the extant two patients underwent therapeutic wedge resection. In all patients prethoracoscopic hookwire positioning was successful. In 11 of 12 patients the lesion was accurately localized, while in the extant patient the wire tip was inserted deeper than the nodule. In 3 patients the wire was dislodged before surgery: in all of them a small hemorrhage developed on the visceral pleura and wedge resection was likewise possible. Four patients had a small pneumothorax which was not treated before surgery. In conclusion, percutaneous hookwire localization of peripheral lung lesions is an easy and efficacious technique and promotes thoracoscopy as a less invasive alternative to thoracotomy.

Adenocarcinoma↗
PubMed1980

Metastasis: reticuloendothelial system and organ retention of disseminated malignant cells.

The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125l]dUrd-labelled tumor cells into B16 melanomabearing mice. Experiments were performed with mice undergoing acute or chronic reactions to bacterial endotoxin or zymosan, both of which were shown to modify the activity of the reticuloendothelial system as assessed by carbon clearance assays. On the one hand, the release of arrested melanoma cells from the lungs was retarded in mice with both endotoxin-and zymosan- induced acute inflammation. There was a parallel increase in the numbers of pulmonary tumor nodules which developed after injection of non-radiolabelled melanoma cells into similarly treated groups of mice. On the other hand, fewer tumor cells were retained in the lungs of mice undergoing chronic responses to endotoxin, and fewer pulmonary tumor nodules subsequently arose after injection of unlabelled cells. However, in mice pre-treated with zymosan, retention of melanoma cells was not different from that in controls and greatly increased numbers of pulmonary nodules grew in zymosan pre-treated mice receiving non-radiolabelled cells. These experiments were discussed in terms of the contribution of the reticuloendothelial system to the release of arrested cancer cells from the pulmonary vasculature.

Animals↗
PubMed1983

A rapid regulatory response governing nodulation in soybean.

The number of nodules which develop on the primary root of soybean seedlings (Glycine max L. Merr) after inoculation with Rhizobium japonicum is substantially diminished in the region of the root developmentally 10 to 15 hours younger than the region maximally susceptible to nodulation at the time of inoculation. This rapid inhibition of nodulation has been investigated by inoculating soybean seedlings with rhizobia at two different times, 15 hours apart. Living R. japonicum cells, but not heterologous rhizobia or UV-killed cells of the homologous bacterium, were capable of eliciting the rapid inhibitory response. Nodulation responses to varying inoculum concentrations showed that bacterial dosages could be superoptimal, resulting in reduced nodulation and reduced inhibition of nodulation. When suspensions of R. japonicum were dripped uniformly onto the root surfaces, the degree of inhibition of nodulation in developmentally younger regions of the root was correlated with the number of nodules formed in the older and initially most susceptible region of the root. Nodulation in the developmentally younger region of the root, however, was affected very little if the first inoculum was restricted to contact with root cells in the region initially most susceptible to nodulation. The rapid regulatory response may be an important factor contributing to the clustering of nodules in the crown region of soybean roots in field-grown plants and the sparse nodulation commonly observed in younger regions of the root.

Journal Article↗
PubMed1995

Discoid lupus erythematosus lesions developed on lupus erythematosus profundus nodules.

We describe this case of LEP for its unusual way of presentation. It first appeared with a LEP pattern, followed by a typical DLE of the skin, overlying the nodules only. Moreover, our histologic findings showed the typical pattern of lymphocytic lobular panniculitis, with hyaline necrosis of fat, the lymphoid nodule, and even the lymphocytic nuclear "dust." The epidermal changes, with the liquefaction degeneration of the basal cell layer, a moderate follicular hyperkeratosis, and a perivascular and periappendeal lymphocytic infiltrate, were also observed in the abdominal lesion that developed last without clinically evident DLE.

Adult↗
PubMed2000

A Krüppel-like zinc finger protein is involved in nitrogen-fixing root nodule organogenesis.

Mechanisms regulating plant host differentiation of the nitrogen-fixing root nodules remain mostly unknown. Sinorhizobium meliloti induces this process in Medicago sativa in which the Mszpt2-1 gene is expressed in vascular bundles of roots and nodules. This gene codes for a Krüppel-like zinc finger protein, a class of transcription factors involved in many animal developmental processes. Expression of Mszpt2-1 in yeast cells conferred osmotic tolerance. Antisense plants grew normally but developed nonfunctional nodules, in which differentiation of the nitrogen-fixing zone and bacterial invasion were arrested. Hence, a vascular bundle-associated Krüppel-like gene is required for the formation of the central nitrogen-fixing zone of the root nodule.

Amino Acid Sequence↗
PubMed2001

Nodulation of legumes by members of the beta-subclass of Proteobacteria.

Members of the Leguminosae form the largest plant family on Earth, with around 18,000 species. The success of legumes can largely be attributed to their ability to form a nitrogen-fixing symbiosis with specific bacteria known as rhizobia, manifested by the development of nodules on the plant roots in which the bacteria fix atmospheric nitrogen, a major contributor to the global nitrogen cycle. Rhizobia described so far belong exclusively to the alpha-subclass of Proteobacteria, where they are distributed in four distinct phylogenetic branches. Although nitrogen-fixing bacteria exist in other proteobacterial subclasses, for example Herbaspirillum and Azoarcus from the phylogenetically distant beta-subclass, none has been found to harbour the nod genes essential for establishing rhizobial symbiosis. Here we report the identification of proteobacteria from the beta-subclass that nodulate legumes. This finding shows that the ability to establish a symbiosis with legumes is more widespread in bacteria than anticipated to date.

Betaproteobacteria↗
PubMed2005

Fatal subcutaneous panniculitis-like T-cell lymphoma with interface change and dermal mucin, a dead ringer for lupus erythematosus.

We report a 48-year-old man who presented with ulcerated plaques and nodules of the lower extremities. Skin biopsies revealed a dense lymphocytic infiltrate involving the dermis and the subcutis in a lobular and septal pattern. No overt cytological atypia was present. Notably, several features resembling lupus erythematosus were present, including vacuolar interface change and abundant dermal mucin deposition. The patient developed pulmonary nodules, and a lung biopsy showed a perivascular and interstitial lymphoid infiltrate without overt atypia. The cutaneous and pulmonary lymphoid infiltrates showed similar immunohistochemical profiles: CD3(+) CD4(-) CD8(+/-) CD56(+). Monoclonal rearrangements of the T-cell receptor gamma gene with similar migration patterns were identified from both locations. The patient developed fatal hemophagocytic syndrome, involving liver, spleen, lymph nodes, and bone marrow. This case is one amongst the rare reports of subcutaneous panniculitis-like T-cell lymphoma with systemic involvement.

Dermis↗
PubMed1994

2,3,7,8-Tetrachlorodibenzo-p-dioxin inhibits differentiation of normal diploid rat osteoblasts in vitro.

The influence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent halogenated aromatic hydrocarbon, on the development of bone tissue-like organization in primary cultures of normal diploid calvarial-derived rat osteoblasts was examined. Initially, when placed in culture, these cells actively proliferate while expressing genes associated with biosynthesis of the bone extracellular matrix. Then, post-proliferatively, genes are expressed that render the osteoblast competent for extracellular matrix mineralization and maintenance of structural as well as functional properties of the mature bone-cell phenotype. Our results indicate that, in the presence of TCDD, proliferation of osteoblasts was not inhibited but post-confluent formation of multicellular nodules that develop bone tissue-like organization was dramatically suppressed. Consistent with TCDD-mediated abrogation of bone nodule formation, expression of alkaline phosphatase and osteocalcin was not upregulated post-proliferatively. These findings are discussed within the context of TCDD effects on estrogens and vitamin D-responsive developmental gene expression during osteoblast differentiation and, from a broader biological perspective, on steroid hormone control of differentiation.

Animals↗
PubMed1994

Genomic structure, expression and evolution of the alfalfa aspartate aminotransferase genes.

Genomic clones encoding two isozymes of aspartate aminotransferase (AAT) were isolated from an alfalfa genomic library and their DNA sequences were determined. The AAT1 gene contains 12 exons that encode a cytosolic protein expressed at similar levels in roots, stems and nodules. In nodules, the amount of AAT1 mRNA was similar at all stages of development, and was slightly reduced in nodules incapable of fixing nitrogen. The AAT1 mRNA is polyadenylated at multiple sites differing by more than 250 bp. The AAT2 gene contains 11 exons, with 5 introns located in positions identical to those found in animal AAT genes, and encodes a plastid-localized isozyme. The AAT2 mRNA is polyadenylated at a very limited range of sites. The transit peptide of AAT2 is encoded by the first two and part of the third exon. AAT2 mRNA is much more abundant in nodules than in other organs, and increases dramatically during the course of nodule development. Unlike AAT1, expression of AAT2 is significantly reduced in nodules incapable of fixing nitrogen. Phylogenetic analysis of deduced AAT proteins revealed 4 separate but related groups of AAT proteins; the animal cytosolic AATs, the plant cytosolic AATs, the plant plastid AATs, and the mitochondrial AATs.

Amino Acid Sequence↗
PubMed2005

Congenital adrenal hyperplasia in adulthood: do men need to continue treatment?

Due to early diagnosis and appropriate paediatric treatment, internists and endocrinologists are now caring for an increasing number of adult patients with congenital adrenal hyperplasia (CAH). Problems that may be encountered in adult males with CAH are the continuing risk of developing an adrenal crisis and impaired gonadal function due to suppression of the hypothalamic-gonadal axis. Fertility may be further compromised by testicular adrenal rest tumours. Available data suggest that the reversal of infertility is more difficult once testicular nodules have developed. Similar to female CAH patients, male patients may develop adrenal tumours due to inadequate adrenocorticotropic hormone suppression. We therefore recommend continuous treatment of male CAH patients with careful monitoring of clinical and hormonal parameters in order to avoid overtreatment.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

The effect of deferoxamine on ciprofibrate-induced hepatocarcinogenesis in the rat.

BACKGROUND: Peroxisome proliferators (PP) are proven hepatocarcinogens in rats and mice. The carcinogenic effect of PP has been attributed to the oxidative stress that results from generation of high levels of hydrogen peroxide (H2O2). Since the hydroxyl radical is produced via metal mediated reaction from H2O2 and is DNA reactive, we have examined the effect of deferoxamine, the specific iron chelator, on ciprofibrate-induced hepatocarcinogenesis. MATERIALS AND METHODS: Male F-344 rats were fed a diet containing ciprofibrate (0.025%) alone or ciprofibrate plus deferoxamine (0.3% or 0.6%) for 60 to 61 weeks, and the livers were analyzed for the incidence, number and size of the tumors. RESULTS: One hundred percent of rats in all groups developed neoplastic nodules and hepatocellular carcinomas. However, in rats given a higher dose of deferoxamine there was a significant decrease in the number of tumors per liver and the number of tumors larger than 10mm. CONCLUSIONS: Although deferoxamine did not prevent tumor development, at the higher dose level it caused a decrease in the number of tumors. These findings indicate that the decreased tumor numbers maybe due to a reduction in the level of hydroxyl radicals.

Animals↗
PubMed1993

Rhizobium NodB protein involved in nodulation signal synthesis is a chitooligosaccharide deacetylase.

The common nodulation genes nodABC are conserved in all rhizobia and are involved in synthesis of a lipooligosaccharide signal molecule. This bacterial signal consists of a chitooligosaccharide backbone, which carries at the nonreducing end a fatty acyl chain. The modified chitooligosaccharide molecule triggers development of nodules on the roots of the leguminous host plant. To elucidate the specific role of the NodB protein in nodulation factor synthesis, we have purified recombinant NodB and determined its biochemical role by direct assays. Our data show that the NodB protein of Rhizobium meliloti deacetylates the nonreducing N-acetylglucosamine residue of chitooligosaccharides. The monosaccharide N-acetylglucosamine is not deacetylated by NodB. In the pathway of Nod factor synthesis, deacetylation at the nonreducing end of the oligosaccharide backbone may be a necessary requirement for attachment of the fatty acyl chain.

Acetylglucosamine↗
PubMed1989

Disseminated fat necrosis: a rehabilitation challenge.

Disseminated fat necrosis (DFN) is a rare complication of pancreatic disease characterized by subcutaneous nodules, visceral effusions, osseous intramedullary fat necrosis, and arthritis. The rehabilitation of a 33-year-old patient with DFN is described here. The patient had a history of alcoholic pancreatitis for which she underwent a subtotal pancreatectomy. Three months later she developed subcutaneous nodules and migratory polyarthralgias. The diagnosis of DFN as the etiology of her arthritis was confirmed by synovial fluid analysis; in addition, magnetic resonance imaging of her long bones revealed multiple marrow infarcts. She was nonambulatory and required assistance with transfers because of severe joint pain. Treatment included local ice, prednisone, methadone, instruction on joint preservation and proper body mechanics, and ambulation with weight-bearing as tolerated with an assistive device. At the patient's discharge, her joint inflammation was clinically improved but not resolved, and she was independent in transfers and ambulation with a walker for short distances. Despite ongoing inflammation, functional improvement was accomplished through a rehabilitation program emphasizing partial weight-bearing ambulation rather than strengthening exercises.

Adult↗
PubMed1985

Induction by paracetamol of bladder and liver tumours in the rat. Effects on hepatocyte fine structure.

Groups of male and female inbred Leeds strain rats were fed diets containing either 0.5% or 1.0% paracetamol by weight for up to 18 months. At the 1.0% dosage level, 20% of rats of both sexes developed neoplastic nodules of the liver, a statistically significant incidence. These rats also showed gross enlargement of their livers and an increase in foci of cellular alteration, the latter also being observed in the low dosage male rats. Papillomas of the transitional epithelium of the bladder developed in all paracetamol-treated groups, and three rats bore bladder carcinomas. However, significant yields of bladder tumours were only obtained from low dosage females and high dosage males. Additionally, 20 to 25% of paracetamol-treated rats developed hyperplasia of the bladder epithelium, which was not coincident with the presence of bladder calculi. A low yield of tumours at various other sites also arose following paracetamol feeding. An electron microscope study of the livers of paracetamol-treated rats revealed ultrastructural changes in the hepatocytes that resemble those that result from exposure to a variety of known hepatocarcinogens.

Acetaminophen↗