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PubMed1999

Early diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis.

OBJECTIVES: Intraventricular astrocytomas (subependymal giant cell astrocytomas) of tuberous sclerosis have a poor prognosis due to the obstruction of CSF flow. The aim of this study was to determine whether they could be differentiated during childhood and at an early preclinical stage, from subependymal nodules without any growing potential. METHODS: The first two MRIs of all children referred to this neuropaediatric centre between 1987 and 1996 were retrospectively blindly reviewed. RESULTS: Out of 60 patients, 24 disclosed subependymal nodules localised near the foramen of Monro, and eight of the 24 developed astrocytomas. Subependymal nodules were first detectable on MRI from 1 year of age in all cases and the first MRI evidence of growth occurred between 1 and 9 years (mean 4 years). At an early stage, subependymal nodules had different characteristics in patients who developed subependymal giant cell astrocytomas from those who did not. The nodules over 5 mm in diameter that were incompletely calcified and enhanced by gadolinium were at higher risk of growing, particularly in children with a familial history of tuberous sclerosis. To detect the subependymal giant cell astrocytomas earlier in tuberous sclerosis, it is advisible to systematically perform an MRI examination before 2 years of age and to repeat it every year if the patient has risk factors for developing astrocytomas.

Brain Neoplasms↗
PubMed1989

Human growth hormone enhances chondrogenesis and osteogenesis in a tissue culture system of chondroprogenitor cells.

GH is a systemic promoter of skeletal growth which increases the synthesis of insulin-like growth factor I in parenchymal tissues as well as in peripheral tissues such as the liver and growing cartilage. The present study was designed to examine whether GH possesses a direct effect on cellular proliferation and differentiation in mouse condylar cartilage. Cartilage progenitor cells were cultured in the form of a tissue culture on top of collagen sponges in medium containing 10% fetal calf serum and were treated with 50 ng/ml GH for 6 days. Three-day incubation with GH caused a marked increase in DNA synthesis and in the size of the culture, which developed into a nodule of differentiated chondrocytes and a well developed perichondrial layer around it. The effect of GH was even more pronounced after 6 days in culture; at which time a distinct network of trabeculae was noted throughout the extracellular matrix. The trabeculae contained osteocyte-like cells and were in close contact with both osteoblast-like and osteoclast-like cells. Using antibodies against bone-specific antigens, i.e. osteocalcin and osteopontin, provided further support for the notion that the newly formed trabecular formation was comprised of bone matrical components. Untreated control cultures lacked such structures, but contained hyaline-like cartilage. It, therefore, seems reasonable to suggest that GH induces a strong stimulatory effect on progenitor cell proliferation, cartilage differentiation, and extracellular mineralization, which supports de novo bone formation in vitro.

Alkaline Phosphatase↗
PubMed1999

The alfalfa (Medicago sativa) TDY1 gene encodes a mitogen-activated protein kinase homolog.

Development of root nodules, specifically induction of cortical cell division for nodule initiation, requires expression of specific genes in the host and microsymbiont. A full-length cDNA clone and the corresponding genomic clone encoding a MAP (mitogen-activated protein) kinase homolog were isolated from alfalfa (Medicago sativa). The genomic clone, TDY1, encodes a 68.9-kDa protein with 47.7% identity to MMK4, a previously characterized MAP kinase homolog from alfalfa. TDY1 is unique among the known plant MAP kinases, primarily due to a 230 amino acid C-terminal domain. The putative activation motif, Thr-Asp-Tyr (TDY), also differs from the previously reported Thr-Glu-Tyr (TEY) motif in plant MAP kinases. TDY1 messages were found predominantly in root nodules, roots, and root tips. Transgenic alfalfa and Medicago truncatula containing a chimeric gene consisting of 1.8 kbp of 5' flanking sequence of the TDY1 gene fused to the beta-glucuronidase (GUS) coding sequence exhibited GUS expression primarily in the nodule parenchyma, meristem, and vascular bundles, root tips, and root vascular bundles. Stem internodes stained intensely in cortical parenchyma, cambial cells, and primary xylem. GUS activity was observed in leaf mesophyll surrounding areas of mechanical wounding and pathogen invasion. The promoter was also active in root tips and apical meristems of transgenic tobacco. Expression patterns suggest a possible role for TDY1 in initiation and development of nodules and roots, and in localized responses to wounding.

3' Untranslated Regions↗
PubMed2000

Pulmonary nodule and aggressive tibialis posterior tenosynovitis in early rheumatoid arthritis.

We report the case of a 34-year-old man with a rheumatoid pulmonary nodule preceding the development of articular symptoms of rheumatoid arthritis. Pulmonary nodules are a well known feature of rheumatoid arthritis and are mostly seen in severe established rheumatoid factor-positive cases. To differentiate between benign and malign pulmonary nodules we discuss the use of positron emission tomography (PET). Despite intensive therapy with steroids and methotrexate in our patient, within months he developed a severe tibialis posterior tendinitis, with partial rupture and evolution to a planovalgus deformity requiring surgery. Both these symptoms are rare but demonstrate the need for close follow-up in early rheumatoid arthritis.

Adult↗
PubMed1996

Adrenocortical nodules in post-mortem series. Development, functional significance, and differentiation from adenomas.

In 498 consecutive autopsy cases, the adrenal glands were light microscopically and morphometrically studied. 265 (53.7%) patients showed single or multiples nodules, 25 (5.0%) adenomas. The diameter of nodules was between 0.3 to 8.0 mm and that of adenomas between 3.2 to 28.0 mm. Clinically, 265 (36.5%) patients revealed arterial hypertension. 283 (63.5%) were normotensive. For the diagnosis of adenomas, the architecture and the cell structure were more important than the size of the tumor. Normotensive patients showed more often (55.%) nodules than hypertensive patients (52.8%). Adenomas were more frequently found in hypertensive patients. There was no correlation between age, sex and nodules, but adenomas were more frequently found in females. Normotensive patients exhibited mainly one nodule, whereas multiple nodules were found in hypertensive patients. In patients with nodules arteriosclerosis with intima hyalinosis was present in 184 (56.3%) cases, in patients without nodules in 81 (47.4%) cases. Our study clearly demonstrates that no correlation exists between the occurrence of adrenocortical nodules and age or hypertension. The etiology of adrenal nodules should be considered together with the arteriopathy.

Adenoma↗
PubMed1980

Development and characterization of mouse hyperplastic mammary outgrowth lines from BALB/cfC3H hyperplastic alveolar nodules.

Five hyperplastic outgrowth lines were developed by serial transplantation of hyperplastic alveolar nodules from BALB/cfC3H mice into BALB/c hosts. The lines were used to study the biology, morphology, and virology of premalignant tissue originating in mouse mammary tumor virus (MuMTV)-positive animals. The five lines differed with respect to tumor potential and growth characteristics, corroborating the previous evidence that MuMTV-positive hyperplastic alveolar nodules are biologically heterogeneous. Subgross and microscopic examination of outgrowths and tumors revealed that each line had unique morphological characteristics. The presence of atypical lobules within the hyperplastic outgrowth appeared to be correlated with tumor risk, and a morphological continuum of atypical lesions ending in overt cancer was suggested. Viral expression was detected by nucleic acid hybridization and immunoperoxidase staining for MuMTV structural antigens. While the MuMTV RNA in certain tissues appeared to vary qualitatively with tumor potential of the outgrowth line, no correlation between viral antigens detected by immunoperoxidase staining and tumor potential was observed.

Animals↗
PubMed1994

[Fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT): newly developed clinical useful method for injecting ethanol into nodules of hepatocellular carcinoma].

We have performed fluoroscopic contrast medium percutaneous ethanol injection therapy (FCM-PEIT) total 266 times to 82 hepatocellular carcinoma (HCC) nodules in 44 HCC cases: FCM-PEIT is the newly developed method that HCC nodules are punctured by a needle and injected with ethanol mixed with water-soluble contrast medium (Iopamidol containing 370 mg/ml iodine) (vol/vol: 7/3) under the fluoroscopic observation as well as ultrasonic diagnostic equipment (US). Autopsy analyses have demonstrated nearly complete tumor necrosis by FCM-PEIT. We analyzed the detectable rate (%) of the contrast medium-mixed ethanol (CME) leakage out of HCC nodules by US-alone, fluoroscope-alone, and US-fluoroscope observation. The detectable rate of the leakage was 63% by US-fluoroscope, while was only 32% by US-alone. Particularly, all leakages into intra hepatic bile duct were missed by US-alone. The maximal CME-amount for injection without any leakage was not uniform and not related to the size of HCC nodules. The present results suggest that FCM-PEIT is clinically more useful method for the treatment of HCC compared to general PEIT that HCC nodules are injected with ethanol under the US-alone observation, since it is easy to confirm whether ethanol can be sufficiently injected into HCC nodules without any leakage.

Carcinoma, Hepatocellular↗
PubMed2002

Multiple Epstein-Barr virus-associated subcutaneous angioleiomyomas in a patient with acquired immunodeficiency syndrome.

Tumours of smooth muscle origin, either solitary or multiple, are occasionally found in immunocompromised patients, particularly in children with acquired immunodeficiency syndrome (AIDS). Most of the reported AIDS-associated leiomyomatous neoplasms have been found in the visceral organs, and the tumour cells all possessed the Epstein-Barr virus (EBV) genome. Here we present a 32-year-old-man with AIDS who developed three skin nodules on his lower left extremity. No other tumorous lesions were found using computed tomography scans. Two of the three nodules were resected for pathological examination. Histologically, both tumours were well circumscribed and located in the subcutis. The tumours were composed of interlacing fascicles of spindle-shaped cells with prominent vasculature and lymphocytic infiltration. No pleomorphism, mitosis or necrosis was seen. Immunohistochemically, the tumour cells were reactive to smooth muscle actin and desmin. Angioleiomyoma was diagnosed. EBV-encoded small RNAs were also demonstrated in the nucleus of the tumour cells by in situ hybridization but no EBV receptor (CD21) or latent membrane protein (LMP)-1 was found in the tumour cells. No human herpesvirus (HHV)-8 genome was detected in the lesion using polymerase chain reaction analysis. The results of this study indicated that EBV containing subcutaneous angioleiomyoma was another neoplasm that must be considered in patients with human immunodeficiency virus infection who develop skin nodules. The role of EBV in the pathogenesis of this unique neoplasm is still unknown.

Acquired Immunodeficiency Syndrome↗
PubMed1978

The effect of ammonium nitrate on the synthesis of nitrogenase and the concentration of leghemoglobin in pea root nodules induced by Rhizobium leguminosarum.

The effects of NH4NO3 on the development of root nodules of Pisum sativum after infection with Rhizobium leguminosarum (strain PRE) and on the nitrogenase activity of the bacteroids in the nodule tissue were studied. The addition of NH4NO3 decreased the nitrogenase activity measured on intact nodules. This reduction of nitrogen fixation did not result from a reduced number of bacteroids or a decreased amount of bacteroid proteins per gram of nodule. The synthesis of nitrogenase, measured as the relative amount of incorporation of [35S]sulfate into the components I and II of nitrogenase was similarly not affected. The addition of NH4NO3 decreased the amount of leghemoglobin in the nodules and there was a quantitative correlation between the leghemoglobin content and the nitrogen-fixing capacity of the nodules. The conclusion is that the decrease of nitrogen-fixing capacity is caused by a decrease of the leghemoglobin content of the root nodules and not by repression of the nitrogenase synthesis.

Enzyme Precursors↗
PubMed2000

Cutaneous pseudolymphoma, lymphomatoid contact dermatitis type, as an unusual cause of symmetrical upper eyelid nodules.

We describe a 74-year-old woman who rapidly developed bilateral voluminous nodules on the upper eyelids, following 4 months' treatment for chalazion. Histological and immunohistochemical findings were suggestive of cutaneous pseudolymphoma (CPL), and extensive screening for malignant lymphoma (ML) remained negative. Cutaneous pseudolymphomas are inflammatory diseases that can simulate ML either clinically, histopathologically, or both. They are a rare cause of nodules of the upper eyelids, usually characterized by a benign evolution, that can be secondary to ultraviolet sensitivity, adverse reactions to systemic medications and contact sensitization, among others. In our case, epicutaneous patch tests were strongly positive for a series of allergens contained in the ophthalmological preparations used; therefore, they were suggestive that the patient had CPL, lymphomatoid contact dermatitis type. In addition, the patient had been treated previously with several drugs, known to cause CPL and immune dysregulation. Complete regression of the lesions required treatment with systemic steroids and chlorambucil. No relapse occurred within a 5-year follow-up period.

Aged↗
PubMed1992

Promoting effect of ovariectomy on hepatocellular tumorigenesis induced in mice by 3'-methyl-4-dimethylaminoazobenzene.

The treatment of female C57BL/6 x DS-F1 mice with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) at 10, 12, 14, 16 and 18 days of age resulted in the development of hepatocellular adenomatous nodules after 10 months of age. Ovariectomy in these mice at 1 month of age hastened the development of adenomatous nodules, which then first appeared at 8 months of age. The incidence of adenomatous nodules in females ovariectomized at the age of 1 month was much higher than that in intact females of the same age. These results showed that the ovaries exerted a suppressive effect on the development of adenomatous nodules. To determine the time from which the ovaries exert this suppressive effect, females were ovariectomized at 4, 6, 8, and 10 months of age, and the incidences of adenomatous nodules were compared at 10 and 12 months of age. Delayed ovariectomy after 8 months of age did decrease the incidence of adenomatous nodules at 10 and 12 months of age, but ovariectomy after 4 and 6 months of age did not. When the incidence of adenomatous nodules in females ovariectomized at 10 months of age was examined over the subsequent 6 months, it became significantly higher after 14 months of age compared with that in intact females. The results show that the ovariectomy has the promoting effect on the development of adenomatous nodules in the liver induced by 3'-Me-DAB after 6 months of age.

Aging↗
PubMed1998

Invasive Trichophyton rubrum resembling blastomycosis infection in the immunocompromised host.

A 55-year-old renal transplant recipient with onychomycosis and chronic tinea pedis presented with tender nodules on his left medial heel. He then developed papules and nodules on his right foot and calf. A skin biopsy demonstrated periodic acid-Schiff (PAS) positive, thick walled round cells, 2 to 6 microm in diameter, in the dermis. Skin biopsy culture grew Trichophyton rubrum. T. rubrum has been described as an invasive pathogen in immunocompromised hosts. The clinical presentation, histopathology, and early fungal culture growth suggested Blastomyces dermititidis in the differential diagnosis before the final identification of T. rubrum.

Blastomycosis↗
PubMed2000

Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study.

Treatment for Hodgkin's disease (HD) is associated with a variety of thyroid abnormalities, including hypothyroidism, hyperthyroidism, and thyroid neoplasms. Due to the small sample size and short follow-up time of most published studies, it has been difficult to appreciate the full extent of the problem and to characterize the interaction between various patient and treatment variables. To overcome these limitations we have assessed thyroid status in 1,791 (959 males) HD survivors from among 13,674 participants in the Childhood Cancer Survivor Study, a cohort of 5-yr survivors of childhood and adolescent cancer diagnosed between 1970 and 1986. Thyroid abnormalities were ascertained as part of a 22-page questionnaire sent to participants. Survivors were a median of 14 yr (range, 2-20 yr) at diagnosis of HD and a median of 30 yr (range, 12-47 yr) at follow-up. Seventy-nine percent of subjects were treated with radiation (median dose of radiation to the thyroid, 3,500 cGy; range, 0.37-5,500 cGy). Control data were available from 2,808 (1,346 males) sibling controls. Thirty-four percent of the entire cohort has been diagnosed with at least one thyroid abnormality. Hypothyroidism was the most common disturbance, with a relative risk of 17.1 (P < 0.0001) compared to sibling controls. Increasing dose of radiation, older age at diagnosis of HD, and female sex were all independently associated with an increased risk of hypothyroidism. Actuarial risk of hypothyroidism for subjects treated with 4,500 cGy or more is 50% at 20 yr from diagnosis. Hyperthyroidism was reported by 5% of survivors, which was 8-fold greater (P < 0.0001) than the incidence reported by the controls. Thyroid dose of 3,500 cGy or more was the only risk factor identified for hyperthyroidism. The risk of thyroid nodules was 27 times (P < 0.0001) that in sibling controls. Female sex and radiation dose to the thyroid of 2,500 cGy or more were independent risk factors for thyroid nodules. The actuarial risk of a female survivor developing a thyroid nodule is 20% at 20 yr from diagnosis. Thyroid cancer was diagnosed in 20 survivors, which is 18 times the expected rate for the general population. After taking into account the possibility that some of the relative risk estimates may be exaggerated due to ascertainment bias, abnormalities of the thyroid are still extremely common in young adult survivors of childhood HD, particularly among females treated with high doses of radiation to the neck.

Adolescent↗
PubMed1979

Localized Ehlers-Danlos syndrome.

A 34-year-old woman had the cutaneous features of the Ehlers-Danlos syndrome, which was strictly limited to the skin and subcutaneous tissue in the region of the left shoulder. The disorder started at approximately age 22 with the development of subcutaneous nodules. Hyperextensibility of the skin in this region developed within the subsequent five years. There was a notable lack of the usually associated joint hyperextensibility, bleeding tendency, scar formation, or the serious systemic components of the Ehlers-Danlos syndrome.

Adult↗
PubMed2004

Construction and validation of cDNA-based Mt6k-RIT macro- and microarrays to explore root endosymbioses in the model legume Medicago truncatula.

To construct macro- and microarray tools suitable for expression profiling in root endosymbioses of the model legume Medicago truncatula, we PCR-amplified a total of 6048 cDNA probes representing genes expressed in uninfected roots, mycorrhizal roots and young root nodules [Nucleic Acids Res. 30 (2002) 5579]. Including additional probes for either tissue-specific or constitutively expressed control genes, 5651 successfully amplified gene-specific probes were used to grid macro- and to spot microarrays designated Mt6k-RIT (M. truncatula 6k root interaction transcriptome). Subsequent to a technical validation of microarray printing, we performed two pilot expression profiling experiments using Cy-labeled targets from Sinorhizobium meliloti-induced root nodules and Glomus intraradices-colonized arbuscular mycorrhizal roots. These targets detected marker genes for nodule and arbuscular mycorrhiza development, amongst them different nodule-specific leghemoglobin and nodulin genes as well as a mycorrhiza-specific phosphate transporter gene. In addition, we identified several dozens of genes that have so far not been reported to be differentially expressed in nodules or arbuscular mycorrhiza thus demonstrating that Mt6k-RIT arrays serve as useful tools for an identification of genes relevant for legume root endosymbioses. A comprehensive profiling of such candidate genes will be very helpful to the development of breeding strategies and for the improvement of cultivation management targeted at increasing legume use in sustainable agricultural systems.

Equipment Design↗
PubMed1986

Two indirect methods for detecting ureide synthesis by nodulated legumes.

Two methods were developed for the detection of altered ureide metabolism in legume nodules. Both techniques are based on the positive correlation between the presence of high xanthine dehydrogenase (EC 1.2.1.37) specific activity in nodules and the ability of those nodules to produce the ureides, allantoin and allantoic acid. In the first method, nodulated legumes are treated for 2 weeks with a soil drench of allopurinol. After allopurinol treatment, leaves of N(2)-fed, ureide-producing legumes, soybean, cowpea, and lima bean, became very chlorotic. Leaves of KNO(3) (-) or NH(4)Cl-fed ureide-producing legumes were unaffected by the allopurinol treatment. Leaves of the amide-producing legumes, alfalfa, clover, peak, and lupin, were unaffected by the allopurinol treatment with N(2), KNO(3), or NH(4)Cl as nitrogen source. These experiments showed that long-term allopurinol treatments are useful in differentiating between ureide- and amide-producing legumes when effectively nodulated. A second method was developed for the rapid, qualitative estimation of xanthine dehydrogenase activity in legume nodules. This method utilizes pterin, an alternate substrate for xanthine dehydrogenase. Xanthine dehydrogenase hydroxylates pterin in the presence of NAD(+) to produce isoxanthopterin. When exposed to long wave ultraviolet light (365 nanometers), isoxanthopterin emits blue fluorescence. When nodules of ureide-producing legumes were sliced in half and placed in microtiter plate wells containing NAD(+) and pterin, isoxanthopterin was observed after 6 hours of incubation at room temperature. Allopurinol prevented isoxanthopterin production. When slices of amide-producing legume nodules were placed in wells with pterin and NAD(+), no blue fluorescence was observed. The production of NADH by xanthine dehydrogenase does not interfere with the fluorescence of isoxanthopterin. These observations agree with the high specific activity of xanthine dehydrogenase in nodules of ureide-producing legumes and the low activity measured in amide-producing nodules. The wild soybean, Glycine soja Sieb. and Zucc., was examined for ureide synthesis. Stems of wild soybean plants had a high ureide abundance with N(2) as sole nitrogen source when nodulated with either Rhizobium fredii or Bradyrhizobium japonicum. Ureide abundance declined when nitrate or ammonium was added to the nutrient solution. Nodule slices of these plants produced isoxanthopterin when incubated with pterin. Nodule crude extracts of G. soja had high levels of xanthine dehydrogenase activity. Both Glycine max and G. soja plants were found to produce ureides when plants were inoculated with fast-growing R. fredii. The two methods described here can be used to discriminate ureide producers from amide producers as well as detect nitrogen-fixing legumes which have altered ureide metabolism. A nodulated legume that lacks xanthine dehydrogenase activity as demonstrated by the pterin assay cannot produce ureides since ureide synthesis has been shown to require xanthine dehydrogenase activity both in vivo and in vitro. A nodulated legume that remains green during allopurinol treatment also lacks ureide synthesis since the leaves of ureide-producing legumes are very chlorotic following allopurinol treatment.

Journal Article↗
PubMed1975

[Unusual isotope scanning aspects of hot thyroid nodules: diagnostic problems].

The classical picture of development of the "hot" nodule, which takes into account at the same time fixing or non-fixing nature of healthy perinodular tissue and the clinical condition of the patient fails to explain certain biological and scintigraphic findings. The authors discuss problems related to scintigraphy which they encounter in the course of the examination. In 174 stimulation tests carried out, 12 resulted in hypofixation of the isotope in the nodule, scintigraphy being carried out in three patients using 99-mTcO4 spontaneous reactivation of healthy tissue was seen in 5 patients. In the light of the cases reported, it would appear that the scintigraphic picture of the "hot" nodule is more in favor of a duality between the latter and healthy tissue with respect to iodine than of a hypersensitivity to TSH. In the 12 inhibition studies carried out, 3 showed the persistence of a contralateral shadow. Finally, on five occasions histological examination of the operative specimen showed the presence of neoplastic change, in two cases within the "hot/ nodule.

Adenocarcinoma↗
PubMed1982

Progression of carcinogen-induced foci of gamma-glutamyltranspeptidase-positive hepatocytes to hepatomas in rats fed a choline-deficient diet.

Following previous findings that feeding a choline-deficient (CD) diet to rat strongly promotes the evolution of liver cells, initiated by a chemical carcinogen, to foci of gamma-glutamyltranspeptidase (gamma GT)-positive hepatocytes, we investigated whether a CD diet could also promote the evolution of gamma GT-positive foci to hepatomas. gamma GT-positive foci were induced in male Sprague-Dawley rats by administration of a single dose of diethylnitrosamine followed by 2 weeks' feeding on a CD diet containing 0.02% acetylaminofluorene. Immediately thereafter, one group of rats was fed a plain CD diet and the other a choline-supplemented (CS) diet, and subgroups of animals were killed periodically for analysis of the number and size of gamma GT-positive foci and development of hepatomas. During the first 7 weeks after switching the diets, the number and size of the foci increased in both groups. At 12 and 16 weeks, the number and size of foci began to decline in rats fed the CS diet. However, in the CD group, there was a progressive increase in the size with coalescence of the foci, as well as development of neoplastic nodules. These lesions were followed at 20 and 28 weeks by development of hepatomas at a high incidence rate. In rats fed the CS diet, a few scattered gamma GT-positive foci, and small neoplastic nodules remained in the liver at 20 and 28 weeks, but no hepatomas developed. These results show that the CD diet is a potent promoter of the evolution of foci of altered hepatocytes to hepatomas, and that most of the gamma GT-positive foci are reversible lesions.

2-Acetylaminofluorene↗