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[A case of infiltration of scar of sarcoidosis after blepharoplasty].

A case of a 28-year-old woman with infiltration of sarcoidosis scar tissue after blepharoplasty is reported. Nodules developed two times in her right upper eyelid about 1 and 2 years after blepharoplasty of both eyes and they were resected each time, but eruption recurred. Ophthalmic examination revealed aqueous flare and cells, snowball vitreous opacities, and retinal periphlebitis. A chest X-ray disclosed bilateral hilar lymphadenopathy (BHL). Laboratory studies showed an elevation of the serum angiotensin converting enzyme (ACE). Light microscopy revealed epithelioid granuloma with no caseation necrosis in a biopsy specimen, Viewing through polarized light demonstrated crystalline-like foreign bodies with bi-refringence in the epithelioid granuloma. Electron microscopic X-ray microanalysis confirmed these foreign bodies to be composed of Si, Mg, and O. These findings indicate that this skin lesion was caused by an infiltration of sarcoidosis scar tissue.

Adult↗

Polyarthritis with cutaneous mucinosis and intrasynovial mucin deposits.

We report the first case of cutaneous and articular mucinosis with presence of mucin deposits within the synovium in an HIV-positive patients. Presentation was asymmetric polyarthritis, and subcutaneous nodules developed two months later. Treatment was with hydroxychloroquine. The outcome of both the skin and joint lesions was favourable.

Adult↗

Role of estrogens as promoters of hepatic neoplasia.

The administration of estrogens to humans has been associated with the development of benign and possibly malignant hepatocellular neoplasms. This study was designed to investigate the mechanism of this association. We present a rat model that demonstrates that stilbestrol (DES) and ethinyl estradiol promote the development of hepatic neoplasms in rats previously initiated with diethylnitrosamine (DEN). Eighty male and 12 female Fischer-344 rats were given a single intraperitoneal injection of either DEN (200 mg. per kg. of body weight) or saline. Beginning 4 weeks after injection, the rats were given an estrogen or corn oil twice weekly for up to 50 weeks. Treatments were stopped at the time of sacrifice or 11 to 29 weeks prior to sacrifice. Estrogen treatments included high dose DES (5 mg. per dose), low dose DES (0.5 mg. per dose), and ethinyl estradiol (0.2 mg. per dose). Male and female rats given both DEN and high dose DES developed grossly visible hepatic hyperplastic nodules (mean, 9.1 per liver) after 20 weeks of DES. Nodules also developed if the onset of DES treatment was delayed until 28 weeks after initiation. Rats given DEN alone or DES alone did not develop nodules after 20 weeks. Microscopic hyperplastic foci also developed in rats given DEN plus DES, DES alone, and DEN alone. The foci in rats given DES alone were largely reversible on cessation of estrogen therapy. Mitotic activity in foci and nodules was prominent during estrogen therapy but declined markedly after cessation of therapy. Similar promoting activity of ethinyl estradiol was observed. Low dose DES was not effective in promoting tumor formation. The data indicate that estrogens promote hepatic neoplasia, perhaps by increasing hepatocyte mitotic activity and thereby facilitating the evolution of previously initiated cells into neoplastic clones. Comparison with human disease should be made with caution, especially because the estrogenic dose administered was approximately 200-fold the usual contraceptive dose in humans. However, the analogy between this model and the development of human oral contraceptive-associated hepatic tumors is evident. It is possible that some women have latent "initiated" cells that divide faster than the surrounding hepatocytes in response to estrogens.

Animals↗

Lectin-like glycoprotein PsNLEC-1 is not correctly glycosylated and targeted in boron-deficient pea nodules.

Symbiosome development was studied in pea root nodules from plants growing in the absence of boron (B). Rhizobia released into the host cells of nodules from B-deficient plants developed to abnormal endophytic forms with an altered electrophoretic lipopolysaccharide pattern. Immunostaining after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting of nodule homogenates with antibodies that recognize glycoprotein components showed that two previously described lectin-like glycoproteins (PsNLEC-1A and PsNLEC-1B) did not harbor the carbohydrate epitope normally recognized by specific monoclonal antibodies. Material derived from B-deficient nodules, however, still contained three antigenic isoforms with similar electrophoretic mobilities to PsNLEC-1 isoforms A, B, and C. These could be detected following immunoblotting and immunostaining with a specific antiserum originating from the purified PsNLEC protein that had been heterologously expressed in Escherichia coli. Immunogold localization of PsNLEC-1 sugar epitopes in B-deficient nodules showed that they were associated mostly with cytoplasmic vesicles rather than normal localization in the symbiosome compartment of mature infected cells. These results suggest that a modification of the glycosyl-moieties of PsNLEC-1 and an alteration of vesicle targeting occur during the development of pea nodules in the absence of B, and that these changes are associated with the development of aberrant nonfunctional symbiosomes.

Animals↗

[Diagnostic strategy for a solitary thyroid nodule. Example of development of recommendations for a practice guideline].

The solitary thyroid nodule is frequently observed and many strategies are proposed for the diagnosis of the etiology and for the choice of treatment. Despite many discussions no clear consensus has been so far reached. The french groups concerned by this problem set up a Clinical Practice Guide line with the methodological help of Agence Nationale pour le Développement de l'Evaluation Médicale. Based upon the critical review of the literature a consensus was obtained concerning the natural history of the nodules and the diagnosis value of the complementary explorations. The clinical approach alone completed by a TSH determination gives the therapeutical choice in about 30% of the patient without any other explorations. In the remaining cases 3 methods (isotope scan, echography, cytopuncture) can be used alone or in a combined sequence. So far no strategy can be privilegiated. It is necessary to set up a systematic comparison between the possible strategies and this will be made by the french thyroid specialists after this first step of delimitation of a clinical practise guide line.

Feasibility Studies↗

New nodulation mutants responsible for infection thread development in Lotus japonicus.

Legume plants develop specialized root organs, the nodules, through a symbiotic interaction with rhizobia. The developmental process of nodulation is triggered by the bacterial microsymbiont but regulated systemically by the host legume plants. Using ethylmethane sulfonate mutagenesis as a tool to identify plant genes involved in symbiotic nodule development, we have isolated and analyzed five nodulation mutants, Ljsym74-3, Ljsym79-2, Ljsym79-3, Ljsym80, and Ljsym82, from the model legume Lotus japonicus. These mutants are defective in developing functional nodules and exhibit nitrogen starvation symptoms after inoculation with Mesorhizobium loti. Detailed observation revealed that infection thread development was aborted in these mutants and the nodules formed were devoid of infected cells. Mapping and complementation tests showed that Ljsym74-3, and Ljsym79-2 and Ljsym79-3, were allelic with reported mutants of L. japonicus, alb1 and crinkle, respectively. The Ljsym82 mutant is unique among the mutants because the infection thread was aborted early in its development. Ljsym74-3 and Ljsym80 were characterized as mutants with thick infection threads in short root hairs. Map-based cloning and molecular characterization of these genes will help us understand the genetic mechanism of infection thread development in L. japonicus.

Flowers↗

Early hepatocellular carcinoma that develops within macroregenerative nodules: growth rate depicted at serial MR imaging.

PURPOSE: To assess by means of magnetic resonance (MR) imaging the growth rate of early hepatocellular carcinoma (HCC) that develops within macroregenerative nodules. MATERIALS AND METHODS: Serial MR imaging was performed in five patients with six macroregenerative nodules that demonstrated a "nodule-within-nodule" pattern (small intranodular focus). The diameter and volume increases of the internal foci at different time intervals were estimated. Average doubling time (DT) was then calculated. RESULTS: The tiny foci within macroregenerative nodules exhibited rapid growth, with average DTs of 29 weeks for diameter and 9.5 weeks for volume. HCC was proved histopathologically in all five patients. CONCLUSION: HCC, which manifests initially as a small focus within a macroregenerative nodule, has the potential for rapid growth. This growth rate should be considered when plans are formulated for follow-up and/or treatment.

Aged↗

Correlation of rectum-associated lymph nodules with the development of experimentally induced acute colonic inflammation in rats.

BACKGROUND AND AIMS: The mechanisms of inflammation in ulcerative colitis occurring initially in the rectum and then extending throughout the colon are still unknown. The aim of this study is to investigate the correlation of rectum-associated lymph nodules (RALN) and the development of a dextran sulfate sodium-induced experimentally acute colonic inflammation in rats. METHODS: We immunohistochemically analyzed the lymph nodules in the rectal region of rats using monoclonal antibodies to specific markers. RESULTS: Rectum-associated lymph nodules resembled the Peyer's patches, where CD4+, CD8+ lymphocytes and Mar 1+ macrophages were observed. After the administration of dextran-sulfate sodium (DSS), RALN showed hypertrophy with an increase in the number of CD4+, CD8+, and interleukin (IL)-2R+ lymphocytes in the periphery, as well as Mar 1+ macrophages in the entire region. Concurrently, platelet/endothelin cell adhesion molecule-1 (PECAM-1+) blood vessels, including high-endothelial venules (HEV), were increased in number in the interfollicular areas. Furthermore, a number of small lymph nodules varying in size were observed in the upper region of the rectum. Some of them were initially confined to the lamina propria mucosae, and became large enough to extend deeper into the tela submucosa. These DSS-induced lymph nodules contained large numbers of CD4+ lymphocytes, IL-2R+ lymphocytes, and Mar 1+ macrophages. CONCLUSIONS: The pathological changes of ulcerative colitis were well correlated with the development of both RALN and DSS-induced lymph nodules. The immunological reaction that occurred in DSS-induced lymph nodules is significantly associated with the expansion of colitis from the lower region of rectum to the upper region of rectum and colon.

Animals↗

Modifying effects of soybean trypsin inhibitor on development of eosinophilic nodules and basophilic foci in the exocrine pancreas of male Sprague-Dawley rats treated with 4-hydroxyaminoquinoline 1-oxide.

Administration of 4-hydroxyaminoquinoline 1-oxide (HAQO) to rats results in development of 2 types of pancreatic acinar lesions, namely eosinophilic nodules and basophilic foci. To cast light on the biological character of these lesions, 5-week-old male Sprague-Dawley rats were given a single intravenous injection of HAQO at a dose of 7 mg/kg and, thereafter, fed soybean trypsin inhibitor (SBTI) at dose levels of 10% and 5%. At week 57, all rats were killed for pathological examination of pancreatic tissue. The incidence of eosinophilic nodules was significantly higher in the HAQO/SBTI group than in the HAQO-alone group, whereas the basophilic acinar foci were observed to occur less frequently and to be smaller in the HAQO/SBTI-treated animals. Administration of SBTI is known to increase the blood level of cholecystokinin, a trophic factor for pancreatic acinar cells. Thus, the present findings suggest that long-term elevation of this endocrine factor can affect the two types of pancreatic acinar lesions in essentially different ways, namely enhancing development of eosinophilic nodules, while suppressing the occurrence of basophilic foci.

4-Hydroxyaminoquinoline-1-oxide↗

Clinical and genetic significance of unilateral Lisch nodules.

PURPOSE: Bilateral Lisch nodules are highly characteristic for neurofibromatosis type 1 (NF1). We wished to study the clinical and genetic implications of unilateral Lisch nodules. METHODS: Retrospective study of the clinical data of 59 patients who received genetic counselling for neurofibromatosis type 1 (NF1) or type 2 (NF2) and were examined at the department of ophthalmology. RESULTS: Unilateral Lisch nodules were observed in 4 cases: one child with NF1 initially presented unilateral Lisch nodules but developed bilateral Lisch nodules by the age of 9. In 2 cases segmental NF1 was the most probable diagnosis and in one case isolated Lisch nodules were observed. Of the 35 NF1 patients 28 ultimately developed bilateral Lisch nodules. Seven NF1 patients did not demonstrate the nodules. At follow-up no Lisch nodules were detected in 2 neurofibromatosis type 2 patients, in 4 patients in whom the diagnosis of NF1 remained doubtful and in 15 patients without NF1. CONCLUSION: Because isolated Lisch nodules are very rare, their presence warrants a thorough patient history and clinical examination to either confirm or exclude generalised or segmental neurofibromatosis type 1.

Adult↗

Synthesis of noncollagenous extracellular matrix proteins during development of mineralized nodules by rat periodontal ligament cells in vitro.

To characterize the mineralized nodules produced by rat periodontal ligament (PDL) cells in vitro, we have studied the synthesis and distribution of mineralized tissue proteins at various stages of nodule formation. PDL cells were obtained from coagulum in the socket at 2 days after tooth extraction and cultured in Dulbecco's Modified Eagles Medium (DMEM) containing 10% fetal bovine serum and antibiotics. Confluent cells were grown in the presence of ascorbic acid (50 micrograms/ml), dexamethasone (5 microM), and beta-glycerophosphate (10 mM) for 3 weeks. Four stages showing distinct morphological characteristics during development of mineralized nodules were identified. Protein synthesis and deposition of proteins into the matrix were studied during these stages by metabolic labeling with [35S]methionine for 24 hours. Large quantities of SPARC (secreted protein, acidic and rich in cysteine) were synthesized by confluent cells but decreased during the progress of mineralized nodule formation. Two forms of osteopontin (OPN) (67 kDa and 61 kDa) were synthesized in comparable quantities by confluent cells; OPN and bone sialoprotein (BSP) were induced by dexamethasone and represented the major proteins in the mineralized matrix. The 67 kDa form of OPN was the predominant species in the mineralized matrix. Both OPN and BSP were localized by immunogold electron microscopy on globular as well as fused electron-dense structures at sites of tissue mineralization.

Animals↗

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↗

Rapid development of hyperplastic nodules and cirrhosis in the liver of rats treated concurrently with thioacetamide and the pyrrolizidine alkaloid lasiocarpine.

Pyrrolizidine alkaloids have long been considered to be hepatotoxic in man as well as in grazing animals. To investigate the effect of liver cell division induced by thioacetamide on the hepatic changes induced by these alkaloids, rats were treated concurrently with thioacetamide and the pyrrolizidine alkaloid lasiocarpine. Thioacetamide was given intraperitoneally in a dose of 50 mg/kg b. wt twice weekly and lasiocarpine was administered in the diet at a concentration of 50 ppm. At 15 weeks, the combination of thioacetamide and lasiocarpine produced numerous grossly visible grey nodules in livers of 26 of 30 rats. Microscopically, these livers revealed a severe degree of postnecrotic cirrhosis and numerous hyperplastic nodules. The cells in most nodules were arranged in solid sheets or in a trabecular pattern and shown atypia, mitosis and hyperchromasia. In contrast, there was no evidence of cirrhosis or nodule formation in livers of animals treated with either lasiocarpine or thioacetamide alone. The rapid development of liver lesions in rats treated simultaneously with low doses of lasiocarpine and thioacetamide suggests that cell proliferation accentuates the development of neoplasia.ł

Acetamides↗

Chalcone reductase-homologous transcripts accumulate during development of stem-borne nodules on the tropical legume Sesbania rostrata.

During a search for genes with induced or enhanced expression in the early stages of development of stem-borne nodules on Sesbania rostrata, a cDNA with homology to chalcone reductase (CHR) genes was isolated. Here, we describe the characterization of a full-length CHR cDNA (Srchr1) and the pattern of CHR transcript accumulation in stem-borne nodules. Expression was correlated with both nodule development and bacterial invasion. In young nodules, CHR transcripts were observed in cells of the parenchyma, in cells around the nodule vascular bundles, and in the uninfected cells of the central tissue.

Alcohol Oxidoreductases↗

Cyclosporine and the development of multiple mammary nodules.

We report here the case of an immunosuppressed patient who developed multiple nodules in both breasts while on cyclosporine therapy. In this case, the benign appearance on imaging and benign clinical course made possible conservative management, thus avoiding invasive diagnostic procedures. For evaluation of these nodes, after cyclosporine was discontinued, the nodules involuted.

Adult↗

A plant regulator controlling development of symbiotic root nodules.

Symbiotic nitrogen-fixing root nodules on legumes are founded by root cortical cells that de-differentiate and restart cell division to establish nodule primordia. Bacterial microsymbionts invade these primordia through infection threads laid down by the plant and, after endocytosis, membrane-enclosed bacteroids occupy cells in the nitrogen-fixing tissue of functional nodules. The bacteria excrete lipochitin oligosaccharides, triggering a developmental process that is controlled by the plant and can be suppressed. Nodule inception initially relies on cell competence in a narrow infection zone located just behind the growing root tip. Older nodules then regulate the number of nodules on a root system by suppressing the development of nodule primordia. To identify the regulatory components that act early in nodule induction, we characterized a transposon-tagged Lotus japonicus mutant, nin (for nodule inception), arrested at the stage of bacterial recognition. We show that nin is required for the formation of infection threads and the initiation of primordia. NIN protein has regional similarity to transcription factors, and the predicted DNA-binding/dimerization domain identifies and typifies a consensus motif conserved in plant proteins with a function in nitrogen-controlled development.

Amino Acid Sequence↗

Contrast-enhanced MR angiography of benign regenerative nodules following TIPS shunt procedure in Budd-Chiari syndrome.

In this report we describe the magnetic resonance (MR) angiographic features of benign hepatic nodules that developed in a patient with Budd-Chiari syndrome, and present the distinguishing features of benign regenerative nodules from hepatocellular cancer. In a 27-year-old woman with chronic Budd-Chiari syndrome, previously non-existing benign nodules developed in the liver parenchyma during the 10-month period following transjugular intrahepatic portosystemic (TIPS) shunt placement. The liver had been examined with gray-scale and Doppler sonography in addition to the MR imaging and MR angiography. On MR angiography, more hepatic nodules became visible in the portal venous phase compared to that of the arterial phase. Delayed washout of contrast medium in nodules was considered to be due to stasis in hepatic sinusoids. Hypervascularization, appearance after portosystemic shunt creation, multiplicity, small size ( <=2 cm in diameter in our patient), presence of peripheral rim, and high signal intensity on T1-weighted images are important imaging features of benign hepatic nodules that develop in patients with Budd-Chiari syndrome.

Adult↗

A severe diabetic nephropathy model with early development of nodule-like lesions induced by megsin overexpression in RAGE/iNOS transgenic mice.

Many factors are involved in the pathogenesis of diabetic nephropathy. A single gene abnormality may be prerequisite but insufficient to the disease to manifest. It is therefore only when a second or sometimes a third damage is associated that the consequences of pathogenic phenotypes become evident. We generated the triple transgenic mice overexpressing megsin (a novel glomerular-specific serpin), a receptor for advanced glycation end products (RAGE), and inducible nitric oxide synthase (iNOS). Compared with the single- or two-gene transgenic mice, the triple transgenic mice developed, at an early age (16 weeks), severe albuminuria and renal damage with all of the characteristics of human diabetic nephropathy (i.e., glomerular hypertrophy, diffuse mesangial expansion, inflammatory cell infiltration, and interstitial fibrosis). Interestingly, 30-40% of glomeruli exhibit nodule-like lesions. Oxidative and carbonyl stress makers (pentosidine, N(epsilon)-carboxymethyllysine, and 8-hydroxy-deoxyguanosine) were significantly higher in the triple transgenic mice. The iNOS transgenic mice have a diabetes phenotype, the renal consequences of which are moot, and the superimposition of RAGE leads to more conspicuous manifestations. By additional overexpression of megsin, a gene known to be involved in mesangial proliferation and expansion, these local consequences become dramatically manifest and approximate those observed in human pathology. This multiple hit approach is of interest in consideration of the sequential events during development of diabetic nephropathy.

Animals↗