Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.
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PMID:Micronodular pneumocyte hyperplasia. 953 75

Aniridia is a rare panocular disorder affecting the cornea, anterior chamber, iris, lens, retina, macula and optic nerve. It occurs because of mutations in PAX6 on band p13 of chromosome 11. It is associated with a number of syndromes, including Wilm's tumour, bilateral sporadic aniridia, genitourinary abnormalities and mental retardation (WAGR) syndrome. PAX6 mutations result in alterations in corneal cytokeratin expression, cell adhesion and glycoconjugate expression. This, in addition to stem-cell deficiency, results in a fragile cornea and aniridia-associated keratopathy (AAK). It also results in abnormalities in the differentiation of the angle, resulting in glaucoma. Glaucoma may also develop as a result of progressive angle closure from synechiae. There is cataract development, and this is associated with a fragile lens capsule. The iris is deficient. The optic nerve and fovea are hypoplastic, and the retina may be prone to detachment. Aniridia is a profibrotic disorder, and as a result many interventions--including penetrating keratoplasty and filtration surgery--fail. The Boston keratoprosthesis may provide a more effective approach in the management of AAK. Guarded filtration surgery appears to be effective in glaucoma. Despite our increasing understanding of the genetics and pathology of this condition, effective treatment remains elusive.
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PMID:Aniridia: current pathology and management. 1893 25

Mammalian target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that is a member of the phosphoinositide 3-kinase (PI3K)-related kinase (PIKK) family. mTOR forms two distinct complexes, mTORC1 and mTORC2. mTORC1 has emerged as a central regulator of cellular metabolism, cell proliferation, cellular differentiation, autophagy and immune response regulation. In contrast to mTORC1, mTORC2, which is not well understood, participates in cell survival and the regulation of actin and cytokeratin organization. In addition, mTORC1 has been implicated in many diseases, including cancer, metabolic diseases, neurological disease, genetic diseases and longevity/aging. One of the diseases resulting from dysfunction of mTORC1 is tuberous sclerosis complex (TSC), which reflects all the symptoms that arise in response to mTORC1 dysfunction. TSC is a multiple hamartomas syndrome with epilepsy, autism, mental retardation and hypopigmented macules that are caused by the constitutive activation of mTORC1 resulting from genetic mutation of TSC1 or TSC2. Inhibitors of mTORC1, such as rapamycin, effectively suppress the symptoms of TSC. This article summarizes the current knowledge on mTOR and the efficacy of mTORC1 inhibitors in the treatment of TSC.
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PMID:Mammalian target of rapamycin and tuberous sclerosis complex. 2605 78

Hemangioblastoma is a well-circumscribed, highly vascular, lipid-rich and low-grade tumor of uncertain histogenesis. Its histopathological features have been well established. Herein, we present a case of cerebellar hemangioblastoma in a 43-year-old woman. Histologically, the tumor was predominantly composed of cellular areas showing eosinophilic or vacuolated stromal cells arranged in nests and sheets. Focally, conventional reticular areas could be seen. Additionally, in some areas, the stromal cells were arranged radially around blood vessels, exhibiting perivascular pseudorosette structures, which were similar mostly to those of ependymomas. Immunohistochemically, the stromal cells markedly showed diffused staining for Vimentin, S-100, CD56, NSE, inhibin-a, podoplanin, alpha-Thalassemia/mental retardation syndrome X and carbonic anhydrase IX, and were negative for cytokeratin, epithelial membrane antigen, oligodendrocyte transcription factor 2, neuronal nuclear antigen, synaptophysin, isocitrate dehydrogenase 1 (R132H), P53 and CD34. Interestingly, the reticular and cellular areas either showed no or individual scattering of the GFAP-positive cells, respectively, while, the perivascular pseudorosette areas strongly and diffusely expressed GFAP. Nuclear mitosis and necrosis were not observed. The MIB-1 antibody labeling index was especially low (about 3%). Based on these findings, the patient was diagnosed with cerebellar hemangioblastoma. In the present case, we documented a distinctive histological appearance of perivascular pseudorosettes in hemangioblastoma and provided the evidence for stromal cells with glial differentiation.
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PMID:Cerebellar hemangioblastoma with perivascular pseudorosette formation and glial differentiation: A case report. 2821 90