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Biomedical subjects

L M Ryan

Publications and source records attributed to L M Ryan.

At least 109 records · Page 6Linked to original sources
PubMed1988

Synovial fluid inorganic pyrophosphate concentration and nucleotide pyrophosphohydrolase activity in basic calcium phosphate deposition arthropathy and Milwaukee shoulder syndrome.

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 crystals, as well as in joints with CPPD crystals. The presence of BCP crystals in synovial fluids was also predictive of elevated NPPH activity.

Calcium Phosphates↗
PubMed1988

Triple crystal disease: monosodium urate monohydrate, calcium pyrophosphate dihydrate, and basic calcium phosphate in a single joint.

A 49 year old man is described with a polyarticular arthritis. Synovial fluid aspirated from the knee joint showed monosodium urate monohydrate and calcium pyrophosphate dihydrate by polarised light microscopy. Additionally, diphosphonate binding and scanning electron microscopy with energy dispersive analysis showed that basic calcium phosphate crystals were also present. This appears to be the first report of three crystals occurring simultaneously in a single joint.

Arthritis↗
PubMed1988

Inorganic pyrophosphate metabolism in arthritis.

Once thought of as a biosynthetic waste product, over the last 2 decades PPi has become understood as an entity with a variety of biologic roles (see Table 1). Documented roles include participation in intracellular Ca++ traffic, mediation of nucleotide and iron transport, storage of molecules in cellular granules, modification of enzyme function, and modulation of mineralization. Much has been established regarding plasma, urine, and synovial fluid levels (see Fig. 1) and urinary excretion in health and disease. Derangements in intracellular PPi content of skin fibroblasts have been noted in patients with CPPD deposition arthropathy (see Table 2). Mechanisms by which elevated PPi concentration develops in synovial fluid from joints with CPPD deposition and related arthropathies have come under scrutiny. The chondrocyte is now recognized as the probable cellular source of intra-articular extracellular PPi (see Figs. 3 and 4). Special attention has been focused on two basic pathways by which chondrocytes could generate extracellular PPi (see Fig. 2). In the first mechanism, chondrocytes demonstrate a set of ectoenzymes which could work in concert to directly produce extracellular PPi. The second pathway involves the major reactions by which PPi is formed within the cell and how intracellular PPi thus formed could be transported into the extracellular space. Much future research is needed regarding these two pathways and their relative importance in the pathogenesis of CPPD crystal deposition and related arthropathies.

Animals↗
PubMed1988

Anterior pituitary involvement in Wegener's granulomatosis.

Wegener's granulomatosis rarely involves the pituitary, and is limited to the posterior gland. A young woman developed sinusitis, otitis media, asymptomatic pulmonary density, blindness, and anterior pituitary hormone deficiency over 7 years. Mucosal biopsies showed only chronic necrotizing inflammation without vasculitis. Since her clinical course suggested an atypical presentation of Wegener's granulomatosis, cyclophosphamide was finally added to corticosteroid therapy. All symptoms but monocular blindness and hypopituitarism remitted.

Adrenal Cortex Hormones↗
PubMed1988

Adults with Ewing's sarcoma. An analysis of 16 patients at the Dana-Farber Cancer Institute.

Between 1975 and 1985, 16 patients with Ewing's sarcoma were treated in the Adult Sarcoma Clinic at the Dana-Farber Cancer Institute. Of 10 patients with extraskeletal or pelvic primaries, 2 (1 pelvic, 1 extraskeletal) are surviving disease-free at 77 and 103 months from diagnosis. Of the six remaining patients, 5 are alive from 38 to 125 months from diagnosis. No relapses were documented after 18 months of disease-free survival. Adults with localized skeletal Ewing's sarcoma outside the pelvis respond well to multimodality therapy. However, pelvic and extraskeletal disease occur in a disproportionately large segment of this older population and are associated with a poor prognosis.

Adolescent↗
PubMed1987

A random phase II study of mitoxantrone and cisplatin in patients with hepatocellular carcinoma. An ECOG study.

Of 86 patients entered in an Eastern Cooperative Oncology Group (ECOG) random Phase II study of mitoxantrone (DHAD) and cisplatin (DDP) in primary liver cancer, 69 were eligible. Nine of the 13 ineligible patients were excluded after a pathology review. Sixty-one percent of the patients were North American, and 39% were South African. The most common severe or the worst toxicity on DHAD was hematologic; and to DDP, hematologic and vomiting. Of the 69 eligible patients, 21 experienced severe, life-threatening or fatal toxic reactions. Two patients treated with DDP had partial responses. With a 95% confidence interval, the true response rate to DHAD was less than 8%, and to DDP, less than 17%. The median survival time was 14 weeks on both drugs. Assuming a proportional hazards model, factors that are significantly associated with survival are patient performance status, the presence of the symptoms, raised bilirubin and hepatomegaly, and clinical evidence of cirrhosis. Any differences between survival rates for South African and North American patients were largely explainable by these factors.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Ecto-nucleoside triphosphate pyrophosphohydrolase activity and calcium pyrophosphate dihydrate crystal deposition disease.

Articular cartilage contains any ectoenzyme activity, NTP-PPH, which is capable of generating PPi from NTP substrates. The PPi generated is from the cleavage of the alpha-beta pyrophosphate bond of NTP and does not result from the effects of NTP catabolites. NTP-PPH activity is expressed on human skin fibroblasts in culture and is significantly increased in subjects with CPPD deposition. In addition, cultured fibroblasts from subjects with CPPD disease have higher intracellular PPi concentrations compared to cells from normals and patients with OA. These results support the hypothesis that alterations in PPi metabolism provide the metabolic basis for CPPD deposition.

Adenine Nucleotides↗
PubMed1986

Rotator cuff tears: preliminary application of high-resolution MR imaging with counter rotating current loop-gap resonators.

A new class of radio frequency (RF) coils for magnetic resonance (MR) imaging and spectroscopy is introduced. The coils consist of two loop-gap resonators of equal diameters positioned along a common axis. They are tuned to the mode in which the current in the two loops flows in opposite directions. These coils are "decoupled" from a uniform excitation field of arbitrary orientation (including circularly polarized fields) by intrinsic decoupling and by means of back-to-back fast recovery diodes. Measurements made with the coils and a phantom saline tank indicate that the signal-to-noise ratio obtainable with these coils is almost identical to that obtained with single loops. Imaging of several anatomic areas, including knee, wrist, and shoulder, has been performed with a 1.5-T MR system that uses circularly polarized RF. A small series of patients with torn rotator cuffs underwent imaging. Difficulties in establishing the diagnosis with MR imaging because of anatomic complexity are illustrated. The value of pulse sequences with long repetition times to increase the signal intensity of fluid in the joint is shown.

Humans↗
PubMed1986

Pyrophosphohydrolase activity and inorganic pyrophosphate content of cultured human skin fibroblasts. Elevated levels in some patients with calcium pyrophosphate dihydrate deposition disease.

In calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, metabolic abnormalities favoring extracellular inorganic pyrophosphate (PPi) accumulation have been suspected. Elevations of intracellular PPi in cultured skin fibroblasts from a single French kindred with familial CPPD deposition (19) and elevated nucleoside triphosphate pyrophosphohydrolase activity (NTPPPH), which generates PPi in extracts of CPPD crystal-containing cartilages (14) favor this suspicion. To determine whether NTPPPH activity or PPi content of cells might be a disease marker expressed in extraarticular cells, human skin-derived fibroblasts were obtained from control donors and patients affected with the sporadic and familial varieties of CPPD (CPPD-S and CPPD-F) deposition. Intracellular PPi was elevated in both CPPD-S (P less than 0.05) and CPPD-F (P less than 0.01) fibroblasts compared with control fibroblasts. Ecto-NTPPPH activity was elevated in CPPD-S (P less than 0.01) but not CPPD-F. Intracellular PPi correlated with ecto-NTPPPH (P less than 0.01). Elevated PPi levels in skin fibroblasts may serve as a biochemical marker for patients with familial or sporadic CPPD crystal deposition disease; ecto-NTPPPH activity further separates the sporadic and familial disease types. Expression of these biochemical abnormalities in nonarticular cells implies a generalized metabolic abnormality.

Calcium Pyrophosphate↗
PubMed1985

Cartilage nucleoside triphosphate pyrophosphohydrolase. II. Role in extracellular pyrophosphate generation and nucleotide metabolism.

Extracellular generation of inorganic pyrophosphate (PPi) in cartilage organ culture is markedly augmented by ATP.ATP, not an ATP metabolite (ADP, AMP, adenosine) is necessary for this augmentation. Excess PPi production is effectively blocked by known inhibitors of nucleoside triphosphate (NTP) pyrophosphohydrolase (EDTA, EGTA, dithiothreitol). Excess 32P-PPi is generated directly from gamma 32P-ATP by cartilage, as substrate and product have similar specific activities. These findings strongly favor ecto-NTP pyrophosphohydrolase as the source of extracellular PPi generation in the presence of NTP. Additionally, active nucleotide and nucleoside catabolism is demonstrated in these cartilage organ cultures.

Adenosine Triphosphate↗
PubMed1985

Adenosine triphosphate pyrophosphohydrolase and neutral inorganic pyrophosphatase in pathologic joint fluids. Elevated pyrophosphohydrolase in calcium pyrophosphate dihydrate crystal deposition disease.

Adenosine triphosphate pyrophosphohydrolase (ATPPPH) and neutral inorganic pyrophosphatase activities were assayed in synovial fluids (SF) from 37 patients with a variety of arthropathies. ATPPPH activity was detected in all fluids, but was highest in patients with chronic chondrocalcinosis; its activity in patients with osteoarthritis was higher than that in patients with rheumatoid arthritis, gout, or pseudogout. ATPPPH activity correlated positively with SF pyrophosphate concentration and negatively with SF white blood cell count. Pyrophosphatase activity did not correlate with diagnosis, pyrophosphate level, or white blood cell count.

Adenosine Triphosphatases↗
PubMed1985

Partial characterization of synovial fluid nucleotide pyrophosphohydrolase.

Synovial fluid adenosine triphosphate pyrophosphohydrolase, an enzyme which manifests increased activity in chondrocalcinosis and osteoarthritis, was partially characterized in synovial fluids from 41 patients who had a variety of arthropathies. Activity was found to be a soluble, heat labile, and divalent cation-dependent nonspecific nucleotide pyrophosphohydrolase with pH optimum 9.0-9.5.

Adenosine Triphosphatases↗
PubMed1985

Statistical analysis of disease onset and lifetime data from tumorigenicity experiments.

We present and discuss several methods for analyzing rodent tumorigenicity experiments. Two approaches are based on the age and tumor status (present/absent) of each animal at the time of death, and assume either that the tumor type is nonlethal or instantly lethal. Two other approaches avoid such restrictive assumptions about tumor lethality by requiring additional types of data. One method assumes that animals are randomly sacrificed at various ages throughout the study. The second approach requires that each animal which develops the tumor be classified as dying either from the tumor or from other causes.

Age Factors↗
PubMed1985

Efficiency of age-adjusted tests in animal carcinogenicity experiments.

Carcinogenicity experiments may be analysed by a simple comparison of the control and exposed groups with respect to the proportions of observed tumors amongst dead animals, when longevity is identical in control and exposed groups. This simple-proportions test is invalid when longevity varies between groups and age-adjusted methods such as the Hoel-Walburg or logrank test are needed. This paper stresses that there is an advantage to using age-adjusted tests, even when the simple-proportions test is valid. The argument is based on calculations of the asymptotic relative efficiency of the simple-proportions test with respect to both the Hoel-Walburg and the logrank tests.

Age Factors↗
PubMed1984

Cartilage nucleoside triphosphate (NTP) pyrophosphohydrolase. I. Identification as an ecto-enzyme.

When 1 mM ATP was added to ambient media of canine cartilage in organ culture or canine chondrocytes in monolayer culture, PPi was generated linearly over 4 hours. The appearance of PPi was related to an ectoenzyme based upon its ability to act upon extracellular substrate, to generate extracellular products, failure to detect enzyme activity in supernatant media, failure to increase activity by cell disruption, and susceptibility to digestion by extracellular trypsin. The enzyme responsible for PPi generation is nucleoside triphosphate (NTP) pyrophosphohydrolase, which acts upon a number of purine and pyrimidine nucleoside triphosphates. This enzyme may play a role in generation of extracellular PPi which participates in calcium pyrophosphate dihydrate crystal formation.

Adenosine Triphosphate↗
PubMed1984

Acute erosive reactive arthritis associated with Campylobacter jejuni-induced colitis.

A case of acute erosive, reactive arthritis following Campylobacter jejuni-induced ulcerative colitis is presented. This is the 12th such case reported in the literature and the first in which destructive lesions of periarticular bone are demonstrated. A review of the literature suggests that reactive arthritis associated with C. jejuni infection is similar to that following other invasive types of bacterial diarrhea and is often associated with HLA-B27 lymphocyte antigen.

Acute Disease↗