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PubMed1991

Mineralized nodule formation in rat bone marrow stromal cell culture without beta-glycerophosphate.

Rat bone marrow stromal cells were cultured in the presence of 10 nM dexamethasone and various concentrations of beta-glycerophosphate. At day 12-15, some nodules consisting of polygonal cells were formed in all culture conditions, and these nodules were mineralized 2-3 days later. beta-Glycerophosphate significantly enhanced nodule formation at concentrations of not less than 5 mM. The mineralized nodules formed in the absence of beta-glycerophosphate were examined using phase-contrast microscopy, undemineralized and demineralized tissue histology, histochemistry for alkaline phosphatase, immunohistochemistry for type I, II, and III collagen, energy dispersive X-ray microanalysis, electron diffraction, and Fourier transform infrared spectroscopy (FT-IR). Mineralized nodules had histological characteristic similar to bone. Cells associated with nodules exhibited high alkaline phosphatase activity, and extracellular matrix of the nodules predominantly consisted of type I collagen. X-Ray microanalysis showed the presence of Ca and P in the mineralized area, and electron diffraction pattern showed the mineral to have apatite crystal structure. Moreover FT-IR indicated that the mineral was a mixture of hydroxyapatite and carbonateapatite. From these observations, it is concluded that the mineralized nodules formed in our culture system are truly bone-like.

Alkaline Phosphatase↗

PubMed1988

The galactosyltransferase activity of hepatic nodules during rat liver carcinogenesis.

Galactosyltransferase has been isolated from putative preneoplastic hepatocyte nodules generated in the resistant hepatocyte model by the procedure of Solt et al. (Am. J. Pathol., 88 (1977) 595-609). The following observations have resulted from these studies: (a) the specific activity of galactosyltransferase isolated from hepatocyte nodules by affinity chromatography was reduced to about 1/3 that of the enzyme in control and in liver tissue surrounding the nodules; (b) the galactosyltransferase activity from normal rat serum eluted from the alpha-lactalbumin affinity column as a single peak (spec. act. = 1.57 nmol/min per mg) while that from the serum of nodule-bearing rats eluted in two distinct peaks (spec. act. = 2.49 and 0.49 nmol/min per mg protein); (c) the elution profile of the enzyme from hepatocyte nodules was broad compared to that from normal liver, surrounding liver or serum; (d) the Km for N-acetyl-D-glucosamine (GlcNAc) was lower in all four independent batches of nodules compared to the Km for GlcNAc from control and surrounding liver; (e) the Km for uridine diphosphogalactose (UDP-Gal) was higher for the enzyme from nodules compared to that from control tissue. These data suggest that the hepatocyte nodule produces several glycoforms of galactosyltransferase the kinetic properties of which differ from those of the enzyme from control liver.

Animals↗

PubMed1985

Cloning of the nodulation (nod) genes of Rhizobium phaseoli and their homology to R. leguminosarum nod DNA.

In Rhizobium phaseoli strain 8002, a large indigenous plasmid, pRP2JI, had previously been shown to carry many of the genes necessary for the induction of nitrogen-fixing nodules on Phaseolus beans. A cosmid clone library was constructed using DNA from strain 8002. From this library, two overlapping recombinant plasmids (pIJ1097 and pIJ1098) were isolated which spanned about 43 kb of pRP2JI DNA. These plasmids could restore nodulation to some, but not all nodulation-deficient strains of R. phaseoli, indicating that the nodulation genes were not clustered within one small region of pRP2JI. The cloned R. phaseoli nodulation region shared extensive DNA homology with the nodulation genes of R. leguminosarum, and on the basis of DNA hybridization, the nitrogenase genes were found to be within 10 kb of the R. phaseoli nodulation genes. Close to the nodulation genes of R. phaseoli was located a sequence that was repeated on pRP2JI but which was not present elsewhere in the genome of strain 8002.

Chromosome Mapping↗

PubMed2007

Computer-aided diagnosis for improved detection of lung nodules by use of posterior-anterior and lateral chest radiographs.

RATIONALE AND OBJECTIVES: We developed a computerized scheme for detection of lung nodules in the lateral views of chest radiographs, in order to improve the overall performance in combination with the computer-aided diagnostic (CAD) scheme for posterior-anterior (PA) views. MATERIALS AND METHODS: We used 106 pairs of PA and lateral views of chest radiographs (122 lung nodules) for development of the CAD scheme. In the CAD scheme for lateral views, initial candidates of lung nodules were identified by use of a nodule enhancement filter based on the edge gradients. Thirty-four image features extracted from the original and the nodule-enhanced images were used for the rule-based scheme and for artificial neural networks (ANNs) for removal of some false-positive candidates. The computer performance was evaluated with a leave-one-case-out test method for ANNs. For PA views, we used the existing CAD scheme, which was trained with one-half of 924 chest images and then tested with the remaining images. RESULTS: When the CAD scheme was applied only to PA views, the sensitivity in the detection of lung nodules was 70.5%, with 4.9 false positives per image. Although the performance of the computerized scheme for lateral views was relatively low (60.7% sensitivity with 1.7 false positives per image), the overall sensitivity (86.9%) was improved (6.6 false positives per two views), because 20 (16.4%) of the 122 nodules were detected only on lateral views. CONCLUSIONS: The CAD scheme by use of lateral-view images has the potential to improve the overall performance for detection of lung nodules on chest radiographs when combined with a conventional CAD scheme for standard PA views.

Diagnosis, Computer-Assisted↗

PubMed2005

Pediatric vocal nodules: correlation with perceptual voice analysis.

OBJECTIVE: To present the epidemiology and correlation with perceptual analysis of vocal nodules in pediatric patients. METHODS: Retrospective review of patients seen in a tertiary care pediatric hospital's voice center from 1996 to 2003. Six hundred and forty-six patients were evaluated with videostroboscopic examinations and perceptual analysis of voice characteristics by speech pathologists. Appropriate treatment was based on the pathology identified. RESULTS: Two hundred and fifty-four patients (40%) with an average age of 7.7 years (range 0.1-19.3 years) were identified as having vocal nodules. Of these, 72% were male. Six patients (2%) were under the age of 7 months. Nodules were most commonly found in males, aged 3-10 years old. Evidence of gastro-esophageal reflux disease was found in one-quarter of patients; hyperfunction of the larynx was seen in three-fourths. Hyperfunction of the larynx correlates with the size of vocal nodules. Distortion of the vocal fold mucosal wave was not present. Perceptual analysis revealed positive correlation of the severity of hoarseness, breathiness, straining and aphonia with the size of vocal nodules. CONCLUSION: The epidemiology and correlation with perceptual voice analysis in pediatric patients with vocal nodules is presented. Hyperfunction of the larynx correlates with nodule size, while the presence of reflux disease does not. The severity of hoarseness, breathiness, straining and aphonia correlates with the size of vocal nodules.

Adolescent↗

PubMed2005

Shoot-applied polyamines suppress nodule formation in soybean (Glycine max).

In legumes, the number of root nodules is controlled by a mechanism called autoregulation. Recently, we found that the foliar brassinosteroid (BR), a plant growth-regulating hormone, systemically regulates the nodule number in soybean plants. In the present study we report that such down-regulation of root nodule formation by a BR may occur through a change of the polyamine contents, with the experimental evidence as follows. The foliar contents of both spermidine (Spd) and spermine (Spm) in the super-nodulating soybean mutant, En6500, were always lower than those in its parent line, Enrei. This lower Spd and Spm content accompanied a striking accumulation of putrescine (Put) in the former plant. This finding indicates that Spd and Spm biosynthesis from their precursor Put is repressed in En6500. The foliar treatments with Spd or Spm of En6500 led to a reduction of both nodule number and root growth. On the other hand, foliar treatment with MDL74038, a specific inhibitor of Spd biosynthesis, apparently increased the root nodule number in Enrei. Foliar application of brassinolide (BL) of En6500 increased the leaf Spd level and reduced the nodule number. These results suggested that BL-induced Spd synthesis in shoots might suppress the root nodule formation.

Brassinosteroids↗

PubMed1982

Solitary thyroid nodules in children and adolescents.

Thirty-nine children and adolescents with a solitary nodule of the thyroid gland were seen over a 16-yr period and 35 had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, of which 27 showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Five of the 27 cold nodules were malignant (18.5%) while no malignancies were present in the warm or hot nodules. Available diagnostic methods of attempting differentiation of benign from malignant solitary nodules are reviewed and an approach to the clinical management of such nodules as derived from our experience is presented.

Adenoma↗

PubMed1999

Immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules.

The histogenesis of meningothelial-like nodule or so-called minute pulmonary chemodectoma remains unclear, with various immunohistochemical analyses giving inconsistent results. We performed an immunohistochemical and clonal analysis of minute pulmonary meningothelial-like nodules. Thirty-one histologically defined meningothelial-like nodules in 14 cases were stained immunohistochemically. One case had multiple lesions with brown pigment granules, which were positively stained with Berlin blue method, indicating the presence of hemosiderin. All meningothelial-like nodules were positive for vimentin and epithelial membrane antigen (EMA), but not for S-100 protein, chromogranin A, or synaptophysin. Five of 13 cases (13 of 28 lesions) were positive for CD68 by KP-1. Ten cases (24 lesions) stained for CD68 by PG-M1 were weakly positive. All lesions were negative for lysozyme, myosin, actin, keratin, and melanoma-associated antigen. Alveolar macrophages were intensely positive for CD68 and lysozyme in all examined cases. We analyzed the clonality of 11 minute pulmonary meningothelial-like nodule lesions in two female cases based on an X-chromosome-linked polymorphic marker, the human androgen receptor gene (HUMARA). The HUMARA was found to be amplified with or without prior digestion by the methylation-sensitive restriction endonuclease HpaII. Six of 11 lesions showed monoclonal expansion. Five lesions in a multiple case showed different patterns of monoclonality. Our findings showed that minute pulmonary meningothelial-like nodules have meningothelial-like and phagocytic characteristics but no muscular phenotype. Furthermore, some minute pulmonary meningothelial-like nodules may show monoclonal expansion, whereas others are polyclonal. Our data indicate that minute pulmonary meningothelial-like nodules are reactive rather than neoplastic.

Biomarkers↗

PubMed2003

Radiological examination for peripheral lung cancers and benign nodules less than 10 mm.

To clarify the differences in radiological findings between primary lung cancers and benign nodules measuring less than 10mm, we examined chest computed tomography (CT) findings. Of 82 patients with solitary pulmonary nodules less than 10mm in diameter who had undergone surgical biopsy, 21 patients with primary lung cancer and 45 patients with benign lesions (9 patients with tuberculosis, 12 with non-specific inflammation, 10 with benign lung tumor, 10 with intrapulmonary lymph nodes and 4 with others) were examined. Seven patients with atypical adenomatous hyperplasia and nine patients with metastatic lung cancer were excluded. Primary lung cancers had an ill-defined tumor margin and spiculation significantly more frequently than benign nodules (P<0.01). Involvement of bronchi or vessels was observed significantly more frequently in primary lung cancers than in benign nodules (P<0.05), while pleural indentation did not show significant differences in frequency. Retrospective chest X-ray or CT films were reviewed for seven patients with primary lung cancers and 12 with benign nodules, with a mean interval of 24+/-17 months. Primary lung cancers enlarged or appeared as new nodules more frequently than benign lung nodules (P<0.05). Among 17 lung cancer patients who underwent mediastinal lymph node dissection, the cancer was at a more advanced stage than T1N0M0 in four (24%). We conclude that ill-defined margins, spiculation, involvement of bronchi or vessels, and tumor enlargement visualized by CT are still important signs of malignancy even for nodules less than 10mm in size. Tumor size, even for lung cancers measuring less than 10mm, is not an indication for limited resection.

Adenocarcinoma↗

PubMedDate not supplied

Solitary necrotic nodule of the liver: a riddle that is difficult to answer.

Solitary necrotic nodule of the liver is an unusual lesion that is often an incidental finding on abdominal imaging, intraoperative examination, or post mortem. Most reported cases of solitary necrotic nodule have been in males, and over three quarters of these lesions have occurred in the right lobe of the liver. Pathologically, solitary necrotic nodule is a benign lesion characterized by a completely necrotic core that is often partly calcified, surrounded by a dense hyalinized fibrous capsule containing elastin fibres. The ultrasound appearance of solitary necrotic nodule is usually of a "target" lesion with a hyperechoic center, while on CT scan they appear as non-enhancing hypodense lesions that are typical of metastatic adenocarcinoma or peripheral cholangiocarcinoma. The impression of malignancy is further enforced with the finding of necrotic cellular material on biopsy and the macroscopically hard and "gritty" nature of the nodules. Currently, permanent histopathology of solitary necrotic nodules is the only accurate method of diagnosis. However, solitary necrotic nodules are usually of a bilobed or lobulated shape that is unusual for malignant liver lesions, and they often lie in close proximity to hepatic inflow structures. Solitary necrotic nodule should be suspected in liver lesions with this configuration, location, and on a biopsy showing a large amount of necrosis.

Adult↗

PubMed2002

Computerized detection of pulmonary nodules in chest radiographs based on morphological features and wavelet snake model.

We have developed a new computer-aided diagnosis scheme for automated detection of lung nodules in digital chest radiographs based on a combination of morphological features and the wavelet snake. In our scheme, two processes were applied in parallel to reduce the false-positive detections after initial nodule candidates were selected. One process consisted of adaptive filtering for enhancement of nodules and suppression of normal lung structures, followed by extraction of conventional morphological features. The other process consisted of a novel approach for elimination of false positives called the edge-guided wavelet snake model. In the latter process, multiscale edges of the candidate nodules were extracted to yield parts of the nodule boundaries. A wavelet snake was then used for fitting of these multiscale edges for approximation of the true boundaries of nodules. A boundary feature called the weighted overlap between the snake and the multiscale edges was calculated and used for elimination of false positives. Finally, the weighted overlap and the morphological features were combined by use of an artificial neural network for efficient reduction of false positives. Our scheme was applied to a publicly available database of digital chest images for pulmonary nodules. Receiver operating characteristic analysis was employed for evaluation of the performance of each process in the scheme. The combined features yielded a large reduction of false positives, and thus achieved a high performance in discriminating between true and false positives. These results show that our new method, in particular the false-positive reduction method based on the wavelet snake, is effective in improving the performance of a computerized scheme for detection of pulmonary nodules in chest radiographs.

Adult↗

PubMed2003

The Lotus japonicus ndx gene family is involved in nodule function and maintenance.

To elucidate the function of the ndx homeobox genes during the Rhizobium-legume symbiosis, two Lotus japonicus ndr genes were expressed in the antisense orientation under the control of the nodule-expressed promoter Psenod12 in transgenic Lotus japonicus plants. Many of the transformants obtained segregated into plants that failed to sustain proper development and maintenance of root nodules concomitant with down-regulation of the two ndx genes. The root nodules were actively fixing nitrogen 3 weeks after inoculation, but the plants exhibited a stunted growth phenotype. The nodules on such antisense plants had under-developed vasculature and lenticels when grown on medium lacking nitrogen sources. These nodules furthermore entered senescence earlier than the wild-type nodules. Normal plant growth was resumed upon external addition of nitrogen. This suggests that assimilated nitrogen is not properly supplied to the plants in which the two ndx genes are down-regulated. The results presented here, indicate that the ndx genes play a role in the development of structural nodule features, required for proper gas diffusion into the nodule and/or transport of the assimilated nitrogen to the plant.

Cell Nucleus↗

PubMed2002

Shoot control of root development and nodulation is mediated by a receptor-like kinase.

In legumes, root nodule organogenesis is activated in response to morphogenic lipochitin oligosaccharides that are synthesized by bacteria, commonly known as rhizobia. Successful symbiotic interaction results in the formation of highly specialized organs called root nodules, which provide a unique environment for symbiotic nitrogen fixation. In wild-type plants the number of nodules is regulated by a signalling mechanism integrating environmental and developmental cues to arrest most rhizobial infections within the susceptible zone of the root. Furthermore, a feedback mechanism controls the temporal and spatial susceptibility to infection of the root system. This mechanism is referred to as autoregulation of nodulation, as earlier nodulation events inhibit nodulation of younger root tissues. Lotus japonicus plants homozygous for a mutation in the hypernodulation aberrant root (har1) locus escape this regulation and form an excessive number of nodules. Here we report the molecular cloning and expression analysis of the HAR1 gene and the pea orthologue, Pisum sativum, SYM29. HAR1 encodes a putative serine/threonine receptor kinase, which is required for shoot-controlled regulation of root growth, nodule number, and for nitrate sensitivity of symbiotic development.

Alleles↗

PubMed2002

Diversity among Bradyrhizobium isolates nodulating yardlong bean and sunnhemp in Guam.

AIMS: To isolate and characterize bradyrhizobia that nodulate yardlong bean and sunnhemp in Guam. METHODS AND RESULTS: Bradyrhizobia populations that nodulate yardlong bean and sunnhemp in Guam were examined for genetic diversity and their relatedness to Bradyrhizobium japonicum and B. elkanii reference strains. Genomic DNA of 58 isolates of Bradyrhizobium spp. was hybridized with B. japonicum nodY and B. elkanii nodK genes. Based on the hybridization patterns, the isolates were classified into three nodY-nodK hybridizing groups. Group I comprised the majority of the isolates and hybridized with nodY whereas group II isolates hybridized with nodK. The group III isolates, that did not hybridize with either nodY or nodK, formed nitrogen-fixing nodules on cowpea but did not nodulate soybean. DNA sequence analysis of a 280-bp fragment of the variable region of the 16S rRNA gene of a few group III isolates showed that these isolates were more similar to Bradyrhizobium spp. than to B. japonicum or B. elkanii. CONCLUSIONS: The majority of the isolates nodulating yardlong bean and sunnhemp in Guam are similar to B. japonicum, although some isolates are similar to Bradyrhizobium spp. that nodulate a miscellaneous group of legumes including cowpea. SIGNIFICANCE AND IMPACT OF THE STUDY: Since both yardlong bean and sunnhemp are nodulated by a range of bradyrhizobia, selection of superior strains may be based on nodulation effectiveness on both legumes.

Bacterial Proteins↗

PubMed1993

Expression of antisense nodulin-35 RNA in Vigna aconitifolia transgenic root nodules retards peroxisome development and affects nitrogen availability to the plant.

A nodulin-35 (N-35) cDNA encoding nodule-specific uricase (EC 1.7.3.3.) was isolated from a Vigna aconitifolia (mothbean) root nodule cDNA library. Sequence analysis of Vigna uricase (VN-35) cDNA revealed 90% homology to that of soybean. The VN-35 cDNA was inserted in the antisense orientation downstream of the caMV-35S promoter, and transgenic hairy roots were formed on Vigna plants using Agrobacterium rhizogenes. Infection with Bradyrhizobium (cowpea) gave rise to root nodules on transgenic hairy roots supported by the wild-type shoot. Expression of antisense VN-35 RNA was detected in transgenic nodules on individual roots using polymerase chain reaction (PCR). The nodules expressing antisense VN-35 RNA were smaller in size and showed lower uricase activity than nodules formed on the hairy roots transformed with a binary vector containing beta-glucuronidase (GUS) gene (used as control), and the plants exhibited nitrogen deficiency symptoms. Ultrastructural analysis and immunogold labeling with antibody against soybean N-35 revealed that the growth of peroxisomes was retarded in transgenic nodules expressing antisense VN-35 RNA. These data suggest that a reduction in ureide biosynthesis limits the availability of symbiotically reduced nitrogen to the plant. The nodules of tropical legumes appear to be specialized in nitrogen assimilation and are developmentally controlled to produce and transport ureides.

Base Sequence↗

PubMed1997

A carbonic anhydrase gene is induced in the nodule primordium and its cell-specific expression is controlled by the presence of Rhizobium during development.

Under nitrogen starvation, Rhizobium meliloti is able to induce nitrogen-fixing nodules on alfalfa roots. Certain alfalfa cultivars spontaneously develop pseudonodules in the absence of bacteria. A transcript, Msca1, expressed in spontaneous and R. meliloti-induced nodules, that codes for a carbonic anhydrase (CA), an enzyme catalyzing the hydration of CO2 has been identified. This is the first CA gene cloned from a non-photosynthetic tissue in plants. Msca1 was activated initially in all cells of the bacterium-induced nodule primordium and was also induced by cytokinin treatment of alfalfa roots. The presence of CA enzymatic activity in different nodule types was demonstrated. Thus, Msca1 is a new early nodulin gene with a function possibly related to the increased amyloplast deposition of the dividing cortical cells. Msca1 transcripts were subsequently found mainly in a peripheral envelope of cells in developing and mature nodules. This novel pattern of gene expression is controlled by the presence of the bacterium inside the nodule. Sucrose synthase and phosphoenol pyruvate carboxylase (PEPC), other genes of the carbon fixation metabolism, were expressed in the same peripheral cells and even more strongly in the nitrogen-fixing region. Analysis of expression patterns of these genes indicated that early CA function may not be related to carbon fixation through PEPC. CA might be acting in pH regulation and/or CO2/HCO3-transport during nodule initiation. Thus, carbonic anhydrase may play different roles at several stages of nodule development and function.

Amino Acid Sequence↗

PubMed2003

Identification and expression of a soybean nodule-enhanced PEP-carboxylase kinase gene (NE-PpcK) that shows striking up-/down-regulation in vivo.

Various isoforms of plant phosphoenolpyruvate carboxylase (PEPC (Ppc)) are controlled post-translationally by an intricate interaction between allosteric regulation and reversible protein phosphorylation. In leaves and root nodules of legumes, these changes in PEPC phosphorylation state are governed primarily by PEPC-kinase (PpcK), a novel, 'minimal but functional' Ser/Thr kinase. To date, this plant-specific kinase has been investigated in molecular terms exclusively in non-leguminous plants, such as Crassulacean-acid-metabolism (CAM) species and Arabidopsis. As an important extension of our earlier biochemical studies on this dedicated kinase and PEPC phosphorylation in soybean (Glycine max) nodules, we now report the molecular cloning of the first legume PpcK from a soybean nodule cDNA library, which encodes a functional, 31.0 kDa PpcK polypeptide. Besides displaying organ, developmental, and spatial expression properties that are strikingly up-regulated in mature nodules, the expression pattern of this transcript is distinct from that of a second soybean PpcK isogene (GmPpcK). The steady-state abundance of this former, nodule-enhanced transcript (NE-PpcK) is markedly influenced by photosynthate supply from the shoots. This latter up-/down-regulation of NE-PpcK transcript level occurs in vivo in concert with the corresponding changes in the nodule PpcK activity, the phosphorylation-state of PEPC, and the abundance of a previously identified, nodule-enhanced transcript (GmPEPC7) that encodes the target enzyme (NE-Ppc). Furthermore, genomic Southern analysis and inspection of the public database indicate that there are at least three distinct PpcK and Ppc isogenes in soybean. Collectively, these and recent findings with Arabidopsis implicate the existence of multiple PpcK-Ppc'expression-partners' in plants, exemplified by NE-PpcK and NE-Ppc in the soybean nodule.

Amino Acid Sequence↗

PubMed1998

Ivermectin influence on the mast cell activity in nodules of onchocerciasis patients.

Onchocercal nodules were stained immunohistochemically using antibodies specific for human mast cells and IgE to elucidate the localization and frequency of mast cells after a single oral dose of 150 microg/kg ivermectin. Tryptase-and chymase-positive mast cells occurred predominantly in mixed inflammatory infiltrates and perivascularly, and never adhered to adult worms or microfilariae. Up to three days after ivermectin, mast cells and IgE-positive cells were markedly increased in the capsular area of nodules containing female worms with embryos and microfilariae compared to untreated nodules. In the centre of these nodules, around the adult Onchocerca volvulus, we found many tryptase-positive cells. More mast cells were IgE-positive than in untreated nodules, equalling the number of tryptase-positive mast cells. There was a clear correlation between the appearance of mast cells and the attacks on damaged microfilariae by eosinophils and macrophages and in the vicinity of adult worms by neutrophils that occur soon after ivermectin treatment. Onchocercomata harbouring female worms with oocytes only revealed, after all treatment intervals, the same mast cell numbers as untreated nodules. In conclusion, during the first three days after administration, ivermectin produces increased numbers of mast cells in nodules harbouring females with embryos and microfilariae, probably as part of an allergic reaction to the attacked microfilariae. Four to 19 days after ivermectin the number of mast cells in the entire nodule is no longer elevated.

Animals↗