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Biomedical subjects

D J McCarty

Publications and source records attributed to D J McCarty.

At least 127 records · Page 7Linked to original sources
PubMed1984

Cultured human monocytes and fibroblasts solubilize calcium phosphate crystals.

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. Synthetic 45Ca 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 involves phagocytosis followed by dissolution in the acidic environment of secondary lysosomes. Study of the mechanism of calcium phosphate solubilization may be important in understanding resorption of extra-osseus as well as osseus calcification. Intracellular release of calcium from calcium phosphate crystals may also explain our previous observation that hydroxyapatite and other calcium-containing crystals are mitogenic stimuli for fibroblasts and synovial cells.

Ammonium Chloride↗
PubMed1984

Histopathological and ultrastructural studies of synovium in Milwaukee shoulder syndrome--a basic calcium phosphate crystal arthropathy.

Light and electron microscopic study of synovial specimens from four patients with the Milwaukee shoulder syndrome disclosed vascular congestion, villous and focal synovial lining cell hyperplasia, occasional giant cells, and fibrin deposition both within and on the surface of the synovium. Although these changes are non-specific, the finding of basic calcium phosphate crystal aggregates in all four cases and the near total absence of an inflammatory reaction are helpful in distinguishing this condition from other types of arthritis. The focal areas of synovial cell hyperplasia may relate to the powerful mitogenic effect of both synthetic and naturally occurring calcium-containing crystals in concentrations found in the synovial fluid of these patients.

Aged↗
PubMed1983

Crystal populations in human synovial fluid. Identification of apatite, octacalcium phosphate, and tricalcium phosphate.

Defatted joint fluid pellets from 4 patients with the "Milwaukee shoulder" syndrome, an aspirate of milky fluid from subcutaneous tissue of a girl with dermatomyositis/calcinosis, and 2 rabbit synovial membranes calcified by calciphylaxis were studied by Fourier transform infrared analysis. This method permits sequential electronic subtraction ("stripping") of known patterns of highly characterized reference compounds from an unknown sample pattern. Collagen and hydroxyapatite, with carbonate partially (1-3%) substituted for phosphate, and to a lesser extent hydroxyl, were found in all samples. Octacalcium phosphate (OCP) was found in all samples except that from a patient with synovial chondromatosis which contained tricalcium phosphate (TCP). Sulfate was found in 2 of the shoulder joint fluid specimens. An unidentified organic phase was present in all samples. This study confirms recent observations by others that pathologic calcifications contain several mineral phases. These data raise the possibility that hydroxyapatite nucleation may be controlled by hydrolytic alteration of precursor calcium phosphate phases such as OCP or TCP. Studies of the biologic effects of synthetic calcium phosphate crystals must take into account the existence of several crystalline phases in natural pathologic calcifications.

Animals↗
PubMed1983

Retrosomatic clefts: computed tomographic appearance.

A case of bilateral clefts in the pedicles of the L1 vertebra, diagnosed by computed tomography, is presented. The differentiation from other clefts located laterally in the neural arch is briefly summarized, and the possible origin of this entity is discussed. It is improbable that the clefts represent persistent neurocentral synchondroses.

Adult↗
PubMed1983

Phagocytosis of hydroxyapatite or calcium pyrophosphate dihydrate crystals by rabbit articular chondrocytes stimulates release of collagenase, neutral protease, and prostaglandins E2 and F2 alpha.

Synthetic hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) microcrystals are phagocytosed by rabbit articular-cartilage chondrocytes in primary culture. The ingestion of crystals greatly stimulated the release of collagenase, neutral protease, and prostaglandins E2 and F2 alpha into the ambient medium. Lactate dehydrogenase was not released by either crystal despite electron microscopic evidence of cell damage by HA crystals (partial loss of phagolysosomal membrane and increased myelin figures). HA, but not CPPD crystals, stimulated release of beta-glucuronidase. HA crystal concentrations from 50 to 200 micrograms ml-1 induced a dose-dependent release of collagenase and of extracellular protein. Both phagocytosis and collagenase release were greatly attenuated when HA crystals were added to the chondrocyte monolayers in the absence of serum. As HA and CPPD crystals have been identified in human articular cartilage in association with degenerative changes, it is possible that the cell-crystal interaction described here may be pathogenetically important.

Animals↗
PubMed1982

Intractable rheumatoid arthritis. Treatment with combined cyclophosphamide, azathioprine, and hydroxychloroquine.

Seventeen patients (15 women, two men) with progressive, erosive seropositive rheumatoid arthritis (RA) refractory to conventional therapy were treated with cyclophosphamide, azathioprine, and hydroxychloroquine sulfate for an average of 27 +/- 19 months (mean +/- SD throughout) (range, five to 60 months). Disease suppression began in 14 patients within three to 16 months (mean, seven months). Five patients achieved complete remission, two had activity in a single joint only, seven had partial disease suppression, and three showed no response. Prednisone dosage was decreased or administration discontinued in nine of ten patients (5.8 +/- 1.2 to 2.7 +/- 3 mg/day). Serial hand roentgenograms showed recortication of erosions in nine patients, with "filling in" of some erosions in three of these. No change was seen in the roentgenograms of five patients, while progressive disease occurred in three instances. Combined therapy with small doses of three drugs, each with proved antirheumatic activity when used separately in larger doses, may provide satisfactory long-term disease control in patients with intractable RA. This regimen is experimental. Proof of efficacy requires a controlled study. Until such data are obtained, this drug combination is not recommended for general use.

Arthritis, Rheumatoid↗
PubMed1982

Enzymatic release of microspheroids containing hydroxyapatite crystals from synovium and of calcium pyrophosphate dihydrate crystals from cartilage.

Incubation of minced, focally calcified, chondromatosis tissue obtained at operation from a patient with Milwaukee shoulder (rotator cuff defect and glenohumeral osteoarthritis associated with synovial fluid, hydroxyapatite crystals in microspheroidal masses, collagenase, and neutral protease) with partially purified mammalian synovial cell collagenase released masses of hydroxyapatite crystals of the same size as those originally found in the patient's synovial fluid. Incubation of mineral articular cartilage obtained from a shoulder joint at arthroplasty for a destructive arthropathy in a patient with generalised calcium pyrophosphate dihydrate (CPPD) crystal deposition with partially purified synovial cell collagenase freed CPPD crystals from their matrix. These data are compatible with a previously postulated mechanism linking microcrystals to destructive arthropathies, that is, crystal endocytosis by synovial cells stimulating collagenase secretion with subsequent enzymatic crystal "strip-mining', releasing additional crystals into the synovial fluid in a self-perpetuating cycle.

Calcium Pyrophosphate↗
PubMed1981

"Milwaukee shoulder"--association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. I. Clinical aspects.

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 undescribed syndrome which we have designated "Milwaukee shoulder."

Aged↗
PubMed1981

"Milwaukee shoulder"--association of microspheroids containing hydroxyapatite crystals, active collagenase, and neutral protease with rotator cuff defects. II. Synovial fluid studies.

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 and neutral protease activities were found in fluids from 5 joints in 3 patients, whereas active collagenase was found in only 1 of 10 fluids from rheumatoid arthritis patients and in none of 3 fluids from patients with osteoarthritis. Neutral protease activities were present in several rheumatoid joint fluids. These findings are compatible with the hypothesis of an enzymatic release of hydroxyapatite crystals from the synovium and endocytosis by synovial macrophage-like cells with subsequent crystal-stimulated release of collagenase and neutral protease into the joint fluid, completing a pathogenetic cycle.

Aged↗
PubMed1981

"Milwaukee shoulder"--association of microspheroids containing hydroxyapatite crystals, active collagenase, ad neutral protease with rotator cuff defects. III. Morphologic and biochemical studies of an excised synovium showing chondromatosis.

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. Fibrocytes demonstrated intensive pinocytotic activity of unknown significance. Energy dispersive analysis showed elemental ratios consistent with hydroxyapatite. A literature review suggested some relationships between the various pathologic lesions present in this joint. Whether similar synovial changes exist in the opposite shoulder joint of this patient and in 3 other subjects with nearly identical clinical, radiographic, and joint fluid findings is not known.

Aged↗
PubMed1981

Clearance of calcium pyrophosphate dihydrate crystals in vivo. III. Effects of synovial hemosiderosis.

Synthetic triclinic calcium pyrophosphate dihydrate crystals, uniformly labeled with 85Sr and 45Ca, were injected into the knee joints of 2 normal adult rabbits and 2 rabbits previously injected repeatedly with autologous blood. The "half clearance time" of the injected crystal mass was 20.4 and 19 days from control joints, nearly identical to previously reported values in 6 rabbits (19.1 +/- 1.4), and 28.8 and 34 days from the joints injected with blood, a significant difference (P less than 0.05). Iron stains showed hemosiderin granules in the superficial synovium in these joints. Electron microscopy showed crystals with a molar calcium/phosphorus ratio of 1.0 and particles containing iron within synovial cells. We hypothesize that the decreased clearance rate from hemosiderotic synovium is due to inhibition of one or more intracellular pyrophosphatases by iron.

Animals↗
PubMed1981

Release of collagenase, neutral protease, and prostaglandins from cultured mammalian synovial cells by hydroxyapatite and calcium pyrophosphate dihydrate crystals.

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 8-fold increase in PGF alpha levels. This mechanism may be important in the pathogenesis of the destructive arthropathies associated with HA and CPPD crystals.

Animals↗
PubMed1981

Release of pyrophosphate by normal mammalian articular hyaline and fibrocartilage in organ culture.

Calcium pyrophosphate dihydrate crystals are found most frequently in fibrocartilaginous tissue and to a lesser extent in hyaline articular cartilage. Previous investigators found that pyrophosphate (PPi) was released into the medium by immature rabbit hyaline cartilage and osteoarthritic human cartilage in organ culture but not by normal human or mature rabbit cartilage. By employing a sensitive fluorometric assay for PPi and correcting for hydrolysis of PPi during the incubations, we detected PPi release by all normal mammalian cartilage studied. PPi release per mg wet weight of lapine and canine cartilage was paralleled by uronic acid production. Meniscal fibrocartilage, the most common site of calcium pyrophosphate deposits, also elaborate PPi.

Animals↗