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A seven-year-old male, who had a retro-peritoneal alveolar rhabdomyosarcoma and was on total parenteral alimentation (TPN) developed multiple pulmonary nodules, indistinguishable from metastases. These proved to be multiple lipid emboli on open biopsy.
A case of cutaneous calcinosis associated with juvenile dermatomyositis is described. The patient was a 3-year-old girl who had been diagnosed as having dermatomyositis at age 1 year. She was treated with prednisolone, but developed multiple calcified nodules in the subcutaneous tissues and intermuscular fascia. These nodules gradually increased in size despite continual therapy with steroids and aluminium hydroxide. Treatment with diltiazem completely suppressed the development of calcinosis.
BACKGROUND: Diffuse sebaceous gland hyperplasia in transplanted buccal mucosa is a very rare condition. We report on a further patient with this entity. PATIENT: In 1953, a now 68-year-old man suffered a severe alkali burn. Transplantation of oral mucosa was performed that same day in order to prevent perforation of the eye. Over the following 45 years, the patient developed multiple yellowish nodules within the grafts. Histologically, these nodules proved to be normally differentiated sebaceous glands. CONCLUSIONS: Diffuse sebaceous gland hyperplasia originating from within oral mucosa and developing over an extended period of time is a clinical entity known as Fordyce's disease. It is this a late complication of mucocutaneous transplantation, and although it constitutes mainly a problem of cosmesis, functionally it can lead to aberrant secretion of sebum.
OBJECTIVE: We evaluated the efficacy of sonographically guided percutaneous injection of ethanol as an alternative to surgery and administration of radioiodine, which have a higher risk of complications, for treatment of autonomously functioning thyroid nodules that may develop hyperthyroidism. SUBJECTS AND METHODS: Sixteen patients between 23 and 67 years of age who had solitary autonomous thyroid nodules were included in the study. The nodules were detected and evaluated using physical examination, measurements of hormonal levels, sonography, and scintigraphy. Sonographically guided percutaneous injection of ethanol was repeated one to two times each week for a total of four to eight treatments. The amount of ethanol used was 0.5-9.0 ml per treatment, depending on the volume of the nodule. RESULTS: Patients were followed up for at least 18 months. Clinical evaluation, including laboratory tests, showed that the patients' signs and symptoms subsided and hormones returned to normal levels in all cases. Scintigrams showed that the normal thyroid tissue that was suppressed before treatment regained normal function. Sonograms showed that the volume of the nodules decreased in 13 of 16 cases. No early or late permanent complications associated with treatment were noted. CONCLUSION: Our results show that sonographically guided percutaneous injection of ethanol can be used as an alternative treatment of autonomous thyroid nodules with the aim of eliminating the possible risk factors of surgery and radioiodine. This method of treatment may be particularly desirable in patients who are poor candidates for surgery and who refuse standard treatment.
"Rheumatoid" subcutaneous nodules that were at one time considered diagnostic of rheumatoid arthritis or rheumatic fever have also been found in individuals withoug known disease, in patients with systemic lupus erythematosus, and in other conditions. In this report, subcutaneous nodules were described in one patient with fibrositis and in another scleroderma. Multiple pathogenic mechanisms are probably responsible for development of these nodules.
Sinorhizobium fredii USDA257 forms nitrogen-fixing nodules on soybean (Glycine max [L.] Merr.) in a cultivar-specific manner. This strain forms nodules on primitive soybean cultivars but fails to nodulate agronomically improved North American cultivars. Soybean cultivar specificity is regulated by the nolXWBTUV locus, which encodes part of a type III secretion system (TTSS). NolX, a soybean cultivar specificity protein, is secreted by TTSS and shows homology to HrpF of the plant pathogen Xanthomonas campestris pv. vesicatoria. It is not known whether NolX functions at the bacterium-plant interface or acts inside the host cell. Antibodies raised against S. fredii USDA257 NolX were used in immunocytochemical studies to investigate the subcellular localization of this protein. Immunostaining of paraffin-embedded sections of developing soybean and cowpea (Vigna unguiculata [L.] Walp) nodules revealed localization of NolX in the infection threads. Protein A-gold immunocytochemical localization studies utilizing affinity-purified NolX antibodies revealed specific deposition of gold particles in the fibrillar material inside infection threads. Similar immunogold localization studies failed to detect NolX in thin sections of mature soybean and cowpea nodules. The results from this study indicate that NolX is expressed in planta only during the early stages of nodule development.
To investigate the legume-Rhizobium symbiosis, we isolated and studied a novel symbiotic mutant of the model legume Medicago truncatula, designated nip (numerous infections and polyphenolics). When grown on nitrogen-free media in the presence of the compatible bacterium Sinorhizobium meliloti, the nip mutant showed nitrogen deficiency symptoms. The mutant failed to form pink nitrogen-fixing nodules that occur in the wild-type symbiosis, but instead developed small bump-like nodules on its roots that were blocked at an early stage of development. Examination of the nip nodules by light microscopy after staining with X-Gal for S. meliloti expressing a constitutive GUS gene, by confocal microscopy following staining with SYTO-13, and by electron microscopy revealed that nip initiated symbiotic interactions and formed nodule primordia and infection threads. The infection threads in nip proliferated abnormally and very rarely deposited rhizobia into plant host cells; rhizobia failed to differentiate further in these cases. nip nodules contained autofluorescent cells and accumulated a brown pigment. Histochemical staining of nip nodules revealed this pigment to be polyphenolic accumulation. RNA blot analyses demonstrated that nip nodules expressed only a subset of genes associated with nodule organogenesis, as well as elevated expression of a host defense-associated phenylalanine ammonia lyase gene. nip plants were observed to have abnormal lateral roots. nip plant root growth and nodulation responded normally to ethylene inhibitors and precursors. Allelism tests showed that nip complements 14 other M. truncatula nodulation mutants but not latd, a mutant with a more severe nodulation phenotype as well as primary and lateral root defects. Thus, the nip mutant defines a new locus, NIP, required for appropriate infection thread development during invasion of the nascent nodule by rhizobia, normal lateral root elongation, and normal regulation of host defense-like responses during symbiotic interactions.
A hybridization procedure was developed to identify Frankia strains inside actinorhizae by direct probing of crushed root nodules. The probe consisted of an indigenous cryptic plasmid. This well-conserved, 8-kilobase plasmid was detected in Frankia isolates that were very close taxonomically (they possessed a very high DNA sequence homology). The probe did not hybridize to the DNA of Frankia isolates which did not carry the plasmid. Endophyte DNA was extracted by a modification of a technique originally developed for the detection of plasmids in Frankia isolates. The hybridization procedure applied to nodules collected in a stand of alder permitted determination of a distribution map of the plasmid-bearing Frankia strains.
To elucidate the mechanisms involved in Rhizobium-legume symbiosis, we examined a novel symbiotic mutant, crinkle (Ljsym79), from the model legume Lotus japonicus. On nitrogen-starved medium, crinkle mutants inoculated with the symbiont bacterium Mesorhizobium loti MAFF 303099 showed severe nitrogen deficiency symptoms. This mutant was characterized by the production of many bumps and small, white, uninfected nodule-like structures. Few nodules were pale-pink and irregularly shaped with nitrogen-fixing bacteroids and expressing leghemoglobin mRNA. Morphological analysis of infected roots showed that nodulation in crinkle mutants is blocked at the stage of the infection process. Confocal microscopy and histological examination of crinkle nodules revealed that infection threads were arrested upon penetrating the epidermal cells. Starch accumulation in uninfected cells and undeveloped vascular bundles were also noted in crinkle nodules. Results suggest that the Crinkle gene controls the infection process that is crucial during the early stage of nodule organogenesis. Aside from the symbiotic phenotypes, crinkle mutants also developed morphological alterations, such as crinkly or wavy trichomes, short seedpods with aborted embryos, and swollen root hairs. crinkle is therefore required for symbiotic nodule development and for other aspects of plant development.
RATIONALE AND OBJECTIVES: We sought to evaluate the potential benefits of a computer-aided detection (CAD) system for detecting lung nodules in multidetector row CT (MDCT) scans. METHODS: A CAD system was developed for detecting lung nodules on MDCT scans and was applied to the data obtained from 15 patients. Two chest radiologists in consensus established the reference standard. The nodules were categorized according to their size and their relationship to the surrounding structures (nodule type). The differences in the sensitivities between an experienced chest radiologist and a CAD system without user interaction were evaluated using a chi2 analysis. The differences in the sensitivities also were compared in terms of the nodule size and the nodule type. RESULTS: A total of 309 nodules were identified as the reference standard. The sensitivity of a CAD system (81%) was not significantly different from that of a radiologist (85%; P > 0.05). The sensitivities of the CAD system for detecting nodules < or = 5 mm in diameter as well as detecting isolated nodules were higher than those of a radiologist (83% vs. 75%, P > 0.05; 93% vs. 76%, P < 0.001). The sensitivities of a radiologist for detecting nodules >5 mm and the nodules attached to other structures were higher than those of a CAD system (98% vs. 79%, P < 0.001; 91% vs. 71%, P < 0.001). There were 28.8 false-positive results of CAD per CT study. CONCLUSION: The CAD system developed in this study performed the nodule detection task in different ways to that of a radiologist in terms of the nodule size and the nodule type, which suggests that the CAD system can play a complementary role to a radiologist in detecting nodules from large CT data sets.
OBJECTIVE: To assess by MR imaging the frequency of hepatic nodules in patients waiting on the liver transplant list and to determine whether certain underlying hepatic diseases were more often associated with the development of such hepatic nodules. MATERIAL AND METHODS: We reviewed the MR and clinical records in all patients seen by the liver transplant service at our center since its inception in January 1998 until September 2002. A total of 371 patients (207 men and 164 women, age range 18-68 years, mean 45 years) were included in the study. The presence of hepatic nodules, size, number and underlying hepatic diseases were determined in all patients. Magnetic resonance imaging was performed on a 1.5-T MR imager using T1-weighted, T2-weighted and multi-phase gadolinium-enhanced sequences. Odds ratio (OR) and 95% confidence intervals (CIs) were computed to evaluate the association between the underlying hepatic disease and the development of hepatic nodule. RESULTS: Among 371 liver transplantation candidates, the most common underlying hepatic disease was hepatitis C virus (HCV) infection, either alone (n=93; 25%) or associated with other hepatic diseases (n=40; 10.8%). Of all patients, 33 (8.9%) had regenerative nodules (RNs), 40 (10.7%) dysplastic nodules (DNs) and 57 (15.3%) hepatocellular carcinomas (HCCs). Hepatocellular carcinoma was observed in 35.3% of patients with HCV infection and alcohol abuse combined, 24.5% with cryptogenic cirrhosis, 25% with hemochromatosis and 19% with alcohol abuse. Patients who had either DNs or HCC were 2.5 times more likely to have either alcohol abuse or HCV, alone or combined, as the substrate of their liver disease (OR 2.54, 95% CI 1.56-4.13). Our data suggest a supra-additive interaction between HCV infection and ethanol in their association with MR imaging detected lesions. CONCLUSION: Patients with cryptogenic cirrhosis, alcohol abuse, HCV infection (alone or combined) and hemochromatosis had the greatest likelihood of having HCC, with the combination of HCV infection and alcohol abuse having the highest of all.
Liver fibrosis results from chronic damage to the liver by chronic hepatitis, alcohol, and toxic agents. A characteristic of liver fibrosis is an accumulation of extracellular matrix (ECM) protein, which distorts the hepatic architecture by forming a fibrous scar, and the subsequent development of regenerating nodules defines cirrhosis. Transforming growth factor (TGF)-beta1, one of the most powerful profibrogenic mediators, plays a major role in the development of liver cirrhosis and regulates ECM gene expression and matrix degradation. This study elucidates the changes of TGF-beta1-mediated signals during liver fibrogenesis by using RNA interference. In this experiment, the TGF-beta1 siRNAs reduced the expression of TGF-beta1 in the livers of CCl(4) injection compared with those of control group, and the expression of type I collagen and alpha-smooth muscle actin was decreased. In conclusion, this study demonstrates that TGF-beta1 siRNAs inhibit TGF-beta1 expression in the murine model of liver cirrhosis and might be a good therapeutic strategy to prevent liver cirrhosis in human.
In order to investigate the role of sphingolipid disruption in the cancer promoting potential of fumonisin B(1) (FB(1)) in the development of hepatocyte nodules, male Fischer 344 rats were subjected to cancer initiation (FB(1) containing diet or diethylnitrosamine (DEN) by i.p. injection) and promotion (2-acetylaminofluorene with partial hepatectomy, 2-AAF/PH) treatments followed by a secondary FB(1) dietary regimen. Sphinganine (Sa) and sphingosine (So) levels were measured by high performance liquid chromatography in control, surrounding and nodular liver tissues of the rats. The disruption of sphingolipid biosynthesis by the secondary FB(1) treatment in the control rats was significantly (P < 0.05) enhanced by the 2-AAF/PH cancer promotion treatment. The nodular and surrounding Sa levels returned to baseline following FB(1) initiation and 2-AAF/PH promotion. When comparing the groups subjected to the secondary FB(1) treatment, the initiation effected by FB(1) was less (P < 0.01) sensitive to the accumulation of Sa in the nodular and surrounding tissues than DEN initiation and the 2-AAF/PH control treatment. In contrast, the So level of FB(1) initiation was marginally increased in the nodules compared to the surrounding liver after 2-AAF/PH promotion and significantly (P < 0.05) higher with the secondary FB(1) treatment. Although, the FB(1)-induced hepatocyte nodules were not resistant to the disruption of sphingolipid biosynthesis, the nodular So levels were increased and might provide a selective growth stimulus possibly induced by bio-active sphingoid intermediates such as sphingosine 1-phosphate (S1P).
Unique organs called nodules form on legume roots in response to intracellular infection by soil bacteria in the genus Rhizobium. This study describes a new MADS box gene, nmhC5, which along with nmh7 (J. Heard and K. Dunn, Proc. Natl. Acad. Sci. USA 92:5273-5277, 1995), is expressed in alfalfa (Medicago sativa) root nodules. Together, these genes represent the first putative transcription factors identified in nodules. Expression in a root-derived structure supports the growing sentiment that MADS box proteins have diverse roles in plant development. Comparison of the putative translation product of nmhC5 with those of other reported members of the MADS box family suggests that the overall structure of nmhC5 is conserved. Evolutionary analysis among the MADS box family showed that nmhC5 is orthologous to a root-expressed clone in Arabidopsis thaliana, agl17, and that nmh7 is similar to the floral subfamily with AP3 (DefA)/PI (Glo). Consistent with a prediction of homodimer formation, NMHC5 was shown to bind a CArG consensus sequence in vitro. In contrast, NMH7, which shows structural similarity to MADS box proteins that form heterodimers, did not bind the CArG element in an in vitro DNA-binding assay, suggesting the existence of an unknown dimer partner. The root-derived MADS box genes constitute a novel subfamily of vegetatively expressed MADS box genes. The evolutionary diversity between nmh7 and nmhC5 could represent an overall mechanistic conservation between plant developmental processes or could mean that nmh7 and nmhC5 make fundamentally different contributions to the development of the nodule.
Transcriptome analysis of Medicago truncatula nodules has led to the discovery of a gene family named NCR (nodule-specific cysteine rich) with more than 300 members. The encoded polypeptides were short (60-90 amino acids), carried a conserved signal peptide, and, except for a conserved cysteine motif, displayed otherwise extensive sequence divergence. Family members were found in pea (Pisum sativum), broad bean (Vicia faba), white clover (Trifolium repens), and Galega orientalis but not in other plants, including other legumes, suggesting that the family might be specific for galegoid legumes forming indeterminate nodules. Gene expression of all family members was restricted to nodules except for two, also expressed in mycorrhizal roots. NCR genes exhibited distinct temporal and spatial expression patterns in nodules and, thus, were coupled to different stages of development. The signal peptide targeted the polypeptides in the secretory pathway, as shown by green fluorescent protein fusions expressed in onion (Allium cepa) epidermal cells. Coregulation of certain NCR genes with genes coding for a potentially secreted calmodulin-like protein and for a signal peptide peptidase suggests a concerted action in nodule development. Potential functions of the NCR polypeptides in cell-to-cell signaling and creation of a defense system are discussed.
The antimetastatic activity of Nocardia rubra cell wall skeleton (N-CWS) with or without cyclophosphamide was examined in an experimental model of pulmonary metastasis induced by Lewis lung carcinoma in C57BL/6 mice. Lewis lung carcinoma cells were implanted into the footpads of mice, and the implanted tumors were removed 9 to 10 days later. Pulmonary metastatic nodules began to develop a few days after the implanted tumor was removed. The inhibitory effect of N-CWS was evaluated from the number of pulmonary surface nodules about 3 weeks after tumor implantation. The antimetastatic activity of N-CWS depended upon the dose, time, and route of its injection. Injection of N-CWS i.v. after removal of the implanted tumor caused the greatest inhibition of development of pulmonary metastases. Therapy with N-CWS plus cyclophosphamide prolonged significantly the survival of mice with metastases. The cytotoxic activities of peritoneal macrophages and macrophages in the lung against Lewis lung carcinoma cells were enhanced in mice treated with N-CWS. Injection i.v. of peritoneal macrophages activated with N-CWS inhibited pulmonary metastases. The role of macrophages in inhibition of micrometastasis in the lung is discussed.
The effects of the composite biopreparation Bralec (involving the soybean-specific root nodule bacterium Bradyrhizobium japonicum strain 634b and soybean lectin at concentrations of 500, 50, and 5 microg/ml as major components) on the development and functional activity of soybean-rhizobium symbiosis (development phases of one leaf, four true leaves, and budding) was studied. It was demonstrated that pretreatment of seed with this preparation stimulated the development of both the macro- and microsymbionts. The experimental plants displayed an active accumulation of biomass (by 4-42% higher compared with the variant with inoculation), development of root nodules (the number increased by 11-110% and the weight, by 27-157%). and elevated nitrogen-fixing activity (by 45-204%). The soybean yield increased by 8-10% upon treatment with Bralec 500 and Bralec 5 as compared with the traditional seed bacterization with root nodule bacteria.
The development of nitrogen-fixing nodules is induced on the roots of legume host plants by Rhizobium bacteria. We employed a novel strategy to probe the underlying mechanism of nodule morphogenesis in alfalfa roots using pTZS, a broad host range plasmid carrying a constitutive trans-zeatin secretion (tzs) gene from Agrobacterium tumefaciens T37. This plasmid suppressed the Nod- phenotype of Rhizobium nodulation mutants such that mutants harboring pTZS stimulated the formation of nodulelike structures. Alfalfa roots formed more or fewer of these nodules according to both the nitrogen content of the environment and the position along the root at which the pTZS+ bacteria were applied, which parallels the physiological and developmental regulation of true Rhizobium nodule formation. This plasmid also conferred on Escherichia coli cells the ability to induce root cortical cell mitoses. Both the pattern of induced cell divisions and the spatially restricted expression of an alfalfa nodule-specific marker gene (MsENOD2) in pTZS-induced nodules support the conclusion that localized cytokinin production produces a phenocopy of nodule morphogenesis.