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1.
AJNR Am J Neuroradiol ; 39(2): 252-259, 2018 Feb.
Article En | MEDLINE | ID: mdl-29191871

BACKGROUND AND PURPOSE: In glioblastoma, tumor-associated macrophages have tumor-promoting properties. This study determined whether routine MR imaging features could predict molecular subtypes of glioblastoma that differ in the content of tumor-associated macrophages. MATERIALS AND METHODS: Seven internally derived MR imaging features were assessed in 180 patients, and 25 features from the Visually AcceSAble Rembrandt Images feature set were assessed in 164 patients. Glioblastomas were divided into subtypes based on the telomere maintenance mechanism: alternative lengthening of telomeres positive (ALT+) and negative (ALT-) and the content of tumor-associated macrophages (with [M+] or without [M-] a high content of macrophages). The 3 most frequent subtypes (ALT+/M-, ALT-/M+, and ALT-/M-) were correlated with MR imaging features and clinical parameters. The fourth group (ALT+/M+) did not have enough cases for correlation with MR imaging features. RESULTS: Tumors with a regular margin and those lacking a fungating margin, an expansive T1/FLAIR ratio, and reduced ependymal extension were more frequent in the subgroup of ALT+/M- (P < .05). Radiologic necrosis, lack of cystic component (by both criteria), and extensive peritumoral edema were more frequent in ALT-/M+ tumors (P < .05). Multivariate testing with a Cox regression analysis found the cystic imaging feature was additive to tumor subtype, and O6-methylguanine methyltransferase (MGMT) status to predict improved patient survival (P < .05). CONCLUSIONS: Glioblastomas with tumor-associated macrophages are associated with routine MR imaging features consistent with these tumors being more aggressive. Inclusion of cystic change with molecular subtypes and MGMT status provided a better estimate of survival.


Brain Neoplasms/diagnostic imaging , Glioblastoma/diagnostic imaging , Macrophages/pathology , Magnetic Resonance Imaging/methods , Adolescent , Adult , Aged , Aged, 80 and over , Brain Neoplasms/mortality , Brain Neoplasms/pathology , Female , Glioblastoma/mortality , Glioblastoma/pathology , Humans , Male , Middle Aged , Prognosis , Regression Analysis , Young Adult
3.
Genes Immun ; 14(3): 162-9, 2013 Apr.
Article En | MEDLINE | ID: mdl-23343931

Matrix metalloproteinases (MMPs) contribute to the joint damage in rheumatoid arthritis (RA). Less is known of the involvement of MMPs at extra-articular sites of rheumatoid inflammation. We assessed the relative contribution from MMP-1, MMP-3, MMP-7 and MMP-12 to joint and extra-articular tissue destruction and inflammation by comparing gene expression in joint synovia and subcutaneous rheumatoid nodules from RA patients. Expression of MMP-1 and MMP-3 predominated in synovia, whereas MMP-12 expression was significantly higher in rheumatoid nodules. Markedly higher MMP-7 expression distinguished a subgroup of nodules that featured infiltrating monocyte/macrophage-producing MMP-7 protein. The high MMP-7 expression in nodules was associated with the single-nucleotide polymorphism (SNP) rs11568818 (-181A>G, MMP-7 promoter) and more active inflammation within the nodule lesions. Patients with such nodules had significantly earlier age of RA onset. Our findings indicate that the expression of MMP-1 and MMP-3 occurs relatively independent of the tissue microenvironment with substantial expression also at extra-articular sites. MMP-12 expression reflects the involvement of monocyte/macrophages in rheumatoid inflammation. Evidence for the association between the rs11568818 SNP and increased MMP-7 expression is restricted to nodules, which indicates that consequences of the MMP-7 polymorphism are likely to manifest within aspects of immune/inflammatory activity that are monocyte/macrophage-mediated.


Arthritis, Rheumatoid/genetics , Gene Expression Regulation, Enzymologic , Matrix Metalloproteinase 12/genetics , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 3/genetics , Matrix Metalloproteinase 7/genetics , Adult , Aged , Arthritis, Rheumatoid/metabolism , Arthritis, Rheumatoid/pathology , Female , Fluorescent Antibody Technique , Humans , Macrophages/metabolism , Male , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 12/metabolism , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinase 7/metabolism , Middle Aged , Monocytes/metabolism , Polymorphism, Single Nucleotide , Reverse Transcriptase Polymerase Chain Reaction , Rheumatoid Nodule/genetics , Rheumatoid Nodule/metabolism , Rheumatoid Nodule/pathology , Synovial Fluid/metabolism , Synovial Membrane/metabolism
5.
J Bone Joint Surg Br ; 86(2): 276-8, 2004 Mar.
Article En | MEDLINE | ID: mdl-15046446

Bilateral, uncemented hip replacements were performed on a 45-year-old woman with autosomal dominant osteopetrosis. The hips showed degenerative changes and protrusio acetabuli. Difficulties were encountered especially during preparation of the femoral canal. At ten-year follow-up she has an excellent clinical and radiological result with no sign of osteolysis. Uncemented hip replacement, while technically demanding, can be successful in the intermediate term for patients with this condition.


Arthroplasty, Replacement, Hip/methods , Osteopetrosis/surgery , Female , Follow-Up Studies , Humans , Middle Aged , Osteopetrosis/diagnostic imaging , Tomography, X-Ray Computed/methods
6.
Pediatr Dev Pathol ; 1(5): 393-404, 1998.
Article En | MEDLINE | ID: mdl-9688764

Two male fetuses (18 and 22 weeks gestation) and a 3-month-old male infant (full sibling of the younger fetus) who were diagnosed with Walker-Warburg syndrome (WWS) on the basis of neuropathologic autopsy findings in brain, eyes, and muscle also had micro-orchia and, microscopically, diffuse gonadoblastoid dysplasia in the testes. Both fetuses also had a miniature left ureter and cystic dysplastic left kidney. Testes from control fetuses of 17-24 weeks gestation with normal karyotype and no central nervous system abnormalities (group A, n = 50), a variety of central nervous system abnormalities (group B, n = 50), or an autosomal aneuploidy syndrome with or without central nervous system abnormalities (group C, n = 30) had no diffuse dysplasia, although a single gonadoblastoid seminiferous tubular profile was present in three controls. Testicular morphology was normal in older fetuses and infants with a wide variety of central nervous system malformations (group D, n = 50). We found no evidence of hypogonadotrophic hypogonadism in the three WWS cases to account for the small penis and incompletely descended testes commonly reported in this condition. We concluded that the apparent specificity of the gonadoblastoid testicular dysplasia to WWS suggests that the gene defect directly affects testicular development.


Abnormalities, Multiple/pathology , Brain/abnormalities , Eye Abnormalities/pathology , Muscular Dystrophies/congenital , Testis/abnormalities , Adult , Biomarkers/analysis , Female , Gestational Age , Humans , Immunoenzyme Techniques , Infant , Male , Muscular Dystrophies/pathology , Pregnancy , Syndrome , Testis/chemistry , Testis/pathology
8.
Chest ; 103(5): 1631-3, 1993 May.
Article En | MEDLINE | ID: mdl-8486069

Two cases of primary pulmonary sarcoma which were initially diagnosed as pulmonary thromboembolism are presented. The clinical and radiologic features of pulmonary sarcoma are reviewed, with special emphasis on the features which distinguish it from thromboembolism.


Carcinosarcoma/diagnosis , Pulmonary Artery , Pulmonary Embolism/diagnosis , Rhabdomyosarcoma/diagnosis , Aged , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Tomography, X-Ray Computed , Vascular Diseases/diagnosis , Ventilation-Perfusion Ratio
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