Daniel J Mccarty

OBJECTIVE: To analyze ANKH in families with calcium pyrophosphate dihydrate crystal deposition disease (CPPD) for disease-causing mutations.

METHODS: Two US families (one of British ancestry and the other of German/Swiss ancestry) with autosomal-dominant CPPD, whose disease phenotypes were found to be linked to chromosome 5p15.1 (locus symbol CCAL2), were screened by direct sequencing for mutations in ANKH, a gene in the CCAL2 candidate interval that has been shown to harbor mutations in ...

Hydroxyapatite crystals in spheroid-shaped masses 1.9-15.6 micrometer in diameter were found in 12 of 13 synovial fluids obtained from the shoulder joints of 4 patients with rotator cuff tears and glenohumeral osteoarthritis. Two of 16 control joint fluids also showed these particles. Collagen types I, II and III were identified in the joint fluid pellets from 3 of the 4 patients, and fibers with typical collagen periodicity were also seen on transmission electronmicroscopy. Collagenase ...

A rapid and relatively simple method for measurement of inorganic pyrophosphate (PPi) in biological samples has been described. The mean +/-SEM of plasma samples from 94 normal subjects was 1.8+/-0.06 muM, giving a normal range (99% confidence limits) of 0.16 - 3.40 mumol/liter. Analysis of 17 plasma samples in duplicate showed a standard deviation of 0.18, giving a 99% probability that a single determination of plasma PPi would be +/-0.68 muM of the true value. The mean PPi levels in ...

Fifty-five samples from knee joints of 44 patients with a wide variety of joint diseases were analyzed by routine gross and microscopic examination, and for pH, pO2 and pCO2; 18 fluids were analyzed for lactate. pO2 values ranged from 8–78 mm Hg. Lower values were found generally in fluids of the inflammatory type. pH values ranged between 6.6 and 7.41 units and correlated poorly with pO2. pCO2 ranged between 34 and 150 mm Hg. pO2 correlated poorly with pCO2 (r = −0.22) but better with ...

Hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) crystals were phagocytosed when added to cultured human rheumatoid or normal canine synovial cells. Collagenase and neutral protease secretion into the culture medium was increased 5- to 8-fold over control values in the presence of HA and increased 3-fold in the presence of CPPD crystals. HA but not CPPD crystals induced a 300-fold increase in human rheumatoid synovial cell culture fluid prostaglandin (PG) E2 levels and an ...

Synovial tissue excised from the unstable right shoulder joint of a patient with an absent rotator cuff, severe glenohumeral joint degeneration, and hydroxyapatite-containing microspherules, collagen types I, II, and III, active collagenase, and neutral protease in the joint fluid showed extensive osteochondromatosis histologically. Electronmicroscopy revealed calcific foci in microvilli which could easily escape into the adjacent joint space through areas denuded of synovial cells. ...

Two rheumatic syndromes associated with deposition of calcium phosphate crystals in soft tissues of the shoulder have prompted us to study the cellular mechanisms of calcium phosphate crystal solubilization. Synthetic45Ca labeled calcium phosphate crystal aggregates were solubilized by cultured human fibroblasts or monocytes. Such solubilization required crystal cell contact and was inhibited by chloroquine and ammonium. We hypothesize that the mechanism of crystal solubilization ...

Serum inorganic pyrophosphate (PPi) levels were consistently two- to threefold higher than plasma PPi prepared from the same blood. PPi was found in platelets in amounts ranging from 1.4 to 3 nmol/10(8) cells, using three different techniques for quantification. These levels are approximately 800 times higher than the mean PPi concentration in normal plasma and approximate the levels of ADP found in platelets by other workers. About 50% of platelet PPi was specifically released ...

Four women, aged 63 to 90 years old, presented with mildly painful shoulders of decreased mobility or stability. Radiographic evidence of a complete tear of the fibrous rotator cuff was present in 7 of 8 shoulder joints. Microspheroids containing hydroxyapatite crystals were seen by scanning electronmicroscopy in 12 of 13 synovial fluid samples. All synovial fluids showed activated collagenase and neutral protease activity. This constellation of findings represents a heretofore ...

Murine peritoneal macrophages were incubated with45Ca-labeled basic calcium phosphate (BCP) crystals in the presence or absence of cytochalasin B. Untreated macrophages solubilized 30–50% of45Ca-BCP in 24 hours. Dissolution began within 3 hours and was linear thereafter. Twenty-three percent of BCP was cell-associated by 3 hours. Endocytosis of crystal occurred continuously throughout the incubation. Endocytosis of crystal did not affect the migration of macrophages through Percoll ...

Synovial fluid (SF) inorganic pyrophosphate (PPi) concentration is elevated in calcium pyrophosphate dihydrate (CPPD) crystal deposition arthropathy. Since CPPD and basic calcium phosphate (BCP) crystals often are present in the same joints, we determined [PPi] and activity of the PPi-generating enzyme, nucleotide pyrophosphohydrolase (NPPH), in SF from the joints of patients with various arthropathies, including those with BCP crystals. We found elevated SF [PPi] in joints with BCP ...