acid-phosphatase and Sclerosis

We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sjögren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity.

Topics: Acid Phosphatase; Animals; Autoimmunity; Bone Diseases, Developmental; Cattle; Chromosomes, Human, Pair 19; Female; Gene Expression Regulation; Humans; Inflammation; Interferon Type I; Isoenzymes; Lupus Erythematosus, Systemic; Male; Models, Molecular; Mutation; Mutation, Missense; Phenotype; Sclerosis; Tartrate-Resistant Acid Phosphatase

It has been suggested that subchondral bone remodeling plays a role in the progression of osteoarthritis (OA). To test this hypothesis, we characterized the changes in the rat anterior cruciate ligament transection (ACLT) model of OA and evaluated the effects of alendronate (ALN), a potent inhibitor of bone resorption, on cartilage degradation and on osteophyte formation.. Male Sprague-Dawley rats underwent ACLT or sham operation of the right knee. Animals were then treated with ALN (0.03 and 0.24 microg/kg/week subcutaneously) and necropsied at 2 or 10 weeks postsurgery. OA changes were evaluated. Subchondral bone volume and osteophyte area were measured by histomorphometric analysis. Coimmunostaining for transforming growth factor beta (TGF beta), matrix metalloproteinase 9 (MMP-9), and MMP-13 was performed to investigate the effect of ALN on local activation of TGF beta.. ALN was chondroprotective at both dosages, as determined by histologic criteria and collagen degradation markers. ALN suppressed subchondral bone resorption, which was markedly increased 2 weeks postsurgery, and prevented the subsequent increase in bone formation 10 weeks postsurgery, in the untreated tibial plateau of ACLT joints. Furthermore, ALN reduced the incidence and area of osteophytes in a dose-dependent manner. ALN also inhibited vascular invasion into the calcified cartilage in rats with OA and blocked osteoclast recruitment to subchondral bone and osteophytes. ALN treatment reduced the local release of active TGF beta, possibly via inhibition of MMP-13 expression in articular cartilage and MMP-9 expression in subchondral bone.. Subchondral bone remodeling plays an important role in the pathogenesis of OA. ALN or other inhibitors of bone resorption could potentially be used as disease-modifying agents in the treatment of OA.

Topics: Acid Phosphatase; Alendronate; Animals; Anterior Cruciate Ligament; Bone Remodeling; Calcinosis; Cartilage, Articular; Collagen; Collagen Type I; Collagen Type II; Disease Models, Animal; Disease Progression; Extracellular Matrix Proteins; Glycoproteins; Isoenzymes; Male; Matrilin Proteins; Osteoarthritis, Knee; Osteoclasts; Peptides; Rats; Sclerosis; Severity of Illness Index; Tartrate-Resistant Acid Phosphatase; Transforming Growth Factor beta

Sclerosing adenosis of the prostate is a rare lesion characterized by the proliferation of variably sized glands in a cellular stroma. We report light microscopic, immunohistochemical, and ultrastructural studies in 22 examples from 15 patients. Two cases were identified in 100 consecutive prostates embedded by a whole organ method, giving a prevalence of 2%. Antibodies directed against the following antigens were used: high-molecular-weight cytokeratin (CKH; 34 beta E12); cytokeratin (CK; AE1/AE3), prostatic acid phosphatase (PAP), prostate-specific antigen (PSA), S-100 protein, muscle-specific actin (HHF35), and vimentin (Vim). Cells within the glandular component demonstrated positive reactivity for CK, CHH, PSA, and PAP, indicating a prostatic epithelial origin. In addition, a distinct population of cells reacting for muscle-specific actin and S-100 protein was identified within this glandular element. Adequate material for ultrastructural study was available in five cases; all showed the presence of flattened cells located between the basement membrane and secretory epithelial cells, which had features typical for myoepithelial differentiation. Although the prostate gland does not normally contain myoepithelial cells, we have documented their consistent presence in this unusual lesion; we believe these cells arise by a metaplastic process from the prostatic basal cells.

Topics: Acid Phosphatase; Actins; Aged; Aged, 80 and over; Antigens, Neoplasm; Cell Differentiation; Epithelium; Humans; Immunohistochemistry; Keratins; Male; Microscopy, Electron; Middle Aged; Muscles; Prostate; Prostate-Specific Antigen; Prostatic Diseases; S100 Proteins; Sclerosis; Vimentin

A prostatic lesion, histologically identical to sclerosing adenosis of the breast, was found in five (1.9%) of 263 patients who underwent transurethral resection, open prostatic adenectomy, radical prostatectomy, or total cystoprostatectomy. This uncommon lesion was a localized proliferation of crowded small glands, small solid nests, and individual cells embedded in a cellular stroma, mimicking a small acinar prostatic adenocarcinoma. The proliferating glands were lined by a single layer of secretory cells surrounded by an eosinophilic membranous structure. Basal cells were disclosed in individual glands or as small nests and even individual cells with immunostainability for basal cell-specific cytokeratin (EAB903), S-100 protein, and muscle-specific actin (HHF35). These findings indicate the benign nature of the lesion with myoepithelial differentiation of the basal cells. In contrast, all 25 small acinar adenocarcinomas examined as controls lacked positive stains for the above three antibodies, verifying the usefulness of these antibodies to distinguish between this benign lesion from adenocarcinoma.

Topics: Acid Phosphatase; Actins; Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Keratins; Male; Prostate-Specific Antigen; Prostatic Diseases; Prostatic Neoplasms; S100 Proteins; Sclerosis

Topics: Acid Phosphatase; Animals; Common Bile Duct; Cystic Fibrosis; Cytoplasmic Granules; Dilatation; Dogs; Endoplasmic Reticulum; Golgi Apparatus; Ligation; Male; Microscopy; Microscopy, Electron; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Sclerosis; Species Specificity