PubMed Health⌕ Search

Biomedical subjects

M Richard

Publications and source records attributed to M Richard.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of metastatic behavior of murine osteosarcoma by hypophysectomy.

BACKGROUND: We recently reported that human osteogenic sarcoma cells are mitogenically responsive in tissue culture to insulin-like growth factor I (IGF-I), a mitogen important in the regulation of cellular proliferation of many tissues, including bone. PURPOSE: The present study was designed to determine whether these in vitro observations could be extended to an in vivo experimental system and whether reduction of IGF-I levels by hypophysectomy could inhibit the aggressive metastatic behavior of osteosarcoma. METHODS: We used standard competitive binding and affinity-labeling techniques to characterize the IGF-I-binding sites of MGH-OGS, a model of human osteosarcoma. Radioimmunoassay of serum, preprocessed to remove IGF-binding proteins, was used to quantitate IGF-I levels. In vitro proliferative response of MGH-OGS cells to IGF-I and other pituitary-dependent factors was determined by thymidine-incorporation experiments. In vivo growth of the neoplasm in 12 hypophysectomized C3H mice and in 14 control C3H mice was determined by serial measurements of implanted tumors and by gross and microscopic examination of the lungs for metastases. RESULTS: MGH-OGS exhibited specific binding sites for 1.39 pmol IGF-I per milligram MGH-OGS cellular membrane protein, a concentration similar to that which we previously reported for human osteosarcoma. In tissue culture, MGH-OGS exhibited mitogenic response to IGF-I (P less than .01) but not to other pituitary-dependent factors. Hypophysectomy reduced levels of circulating IGF-I to 15% of control, significantly inhibited local growth of MGH-OGS tumors (increased time for growth to 1 cm3 from 49 to 84 days, P less than .001), and profoundly inhibited metastatic behavior (decrease in mean number of metastases per host from 16 to less than one; P less than .001). CONCLUSIONS: This study is the first to document the profound inhibitory effect of hypophysectomy on the metastatic behavior of an experimental sarcoma. We conclude that the metastatic behavior exhibited by MGH-OGS osteosarcoma is dependent on pituitary factors, and we suggest that the inhibitory effects of hypophysectomy are related, at least in part, to the reduction of IGF-I levels.

Animals↗
PubMed1992

Evaluation of bepridil efficacy by electrophysiologic testing in patients with recurrent ventricular tachycardia: comparison of two regimens.

The purpose of the study was to evaluate this effect of different doses of intravenous and oral bepridil on the induction of ventricular tachycardia. Thirty-eight patients underwent electrophysiologic evaluation for recurrent ventricular tachycardia (VT). Sustained monomorphic VT was induced by programmed ventricular stimulation, using up to three extrastimuli in all patients. The effects of intravenous bepridil (2 mg/kg) were evaluated during the initial study. Intravenous bepridil prevented the induction of sustained VT in eight patients (21%). Electrophysiologic study was repeated after oral bepridil. In six patients the study was stopped because of adverse effects or VT recurrence. Thirty-two patients underwent repeat study 7 days later, taking oral bepridil, 500 mg/day (n = 16) or 900/day (n = 16). A dose of 500 mg/day of bepridil prevented the induction of sustained VT in only one patient. A dose of 900 mg/day of bepridil prevented the induction of sustained VT in eight patients. There were no significant clinical adverse effects, except in one patient receiving intravenous bepridil. The response to intravenous bepridil did not predict the response to oral bepridil. The response to intravenous or oral bepridil was not related to the plasma level of bepridil but was related to a higher left ventricular ejection fraction. Eight patients (21%) in whom VTs were noninducible on oral bepridil were discharged on 300 mg/day of bepridil if their initial loading dose was 500 mg/day or on 600 mg/day if their initial loading dose was 900 mg/day. They remained free of VT during a follow-up of at least 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Severe hypersensitivity reaction to injectable Gallium 67 in a worker exposed to silica.

Gallium 67 scintigraphy is employed in the evaluation of workers with possible pneumoconiosis. To our knowledge, however, a severe hypersensitivity reaction following the intravenous injection of Gallium 67 has not been described. We report the case of a worker chronically exposed to silica who developed an allergic cutaneous and severe articular reaction following the injection of Gallium 67 while being investigated for possible silicosis. Hilar adenopathy was noted on the chest roentgenogram and, retrospectively, circulating immune complexes were found in the patient's serum. The presence of a positive prick skin test to benzyl alcohol suggests that this preservative caused the hypersensitivity reaction.

Adult↗
PubMed1992

Effect of non-steroidal anti-inflammatory drugs (NSAIDS) on glycosyltransferase activity from human osteoarthritic cartilage.

The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the activity of glycosyltransferases required for the synthesis of the polysaccharide chains of proteoglycans, was studied in human osteoarthritic cartilage in vitro. Using exogenous acceptors, salicylate and indomethacin suppressed the activity of glucuronyl- and xylosyltransferases in a concentration-dependent manner, but had little effect on N-acetylgalactosaminyl- and galactosyltransferases. When used at a concentration derived from the values found in the synovial fluid, salicylate, indomethacin and chloroquine significantly suppressed the activity of glucuronyl- and xylosyltransferases, while tiaprofenic acid, paracetamol (acetaminophen), floctafenine, ketoprofen, ibuprofen and tenoxicam had no effect on the enzymes. An alteration of some glycosyltransferases could explain the reported suppressive effect of some NSAIDs on cartilage proteoglycan synthesis.

Aged↗
PubMed1991

Return of ATP/PCr and EEG after 75 min of global brain ischemia.

Acute, progressive global brain ischemia was induced in awake or anesthetized rats for 5-75 min. Ischemia was achieved with a subclavian-carotid artery occlusion technique (SCOT). After thoracotomy, both subclavian arteries (proximal to their vertebral branches) were tied-off and carotid artery catheter-snares installed. Results show progressive morphological, physiological and neurochemical damage when CBF was reduced from preischemic levels of 115 ml to 0 blood flow. 31P magnetic resonance spectroscopy of high energy phosphate metabolites in vivo showed loss of PCr and beta-ATP signals after 6 min brain ischemia. Energy metabolite levels, EEG and CBF normalized within hours after reperfusion. Degree of neuropathologic damage to hippocampal region appeared linearly related to the ischemic duration of ischemia. Thus, acute global brain ischemia resulted in loss of high energy phosphate metabolites, EEG and neuronal integrity in the hippocampal subfields. Reperfusion following short (5 min) or long (75 min) periods of global brain ischemia induced return of 31P-spectra, EEG and CBF to normal but was unable to reverse all of the neuronal damage at the end of the 72-h observation period.

Adenosine Triphosphate↗
PubMed1991

Calmodulin-dependent collagenase and proteoglycanase activities in chondrocytes from human osteoarthritic cartilage.

Chondrocyte metalloproteinases appear to play a major role in the development of osteoarthritis. The intracellular post-traductional mechanisms regulating collagenase and proteoglycanase are not known. Calmodulin antagonists including phenothiazine and sulfonamide derivatives significantly increased proteoglycanase activity and decreased collagenase activity. H-7, a specific inhibitor of protein kinase C, had no effect on the two metalloproteinase activities, and calmodulin was ineffective in in vitro assays upon metalloproteinase activities. We postulate that collagenase and proteoglycanase activities are controlled by calmodulin-dependent regulation.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

Serotonin-stimulated phospholipase A2 and collagenase activation in chondrocytes from human osteoarthritic articular cartilage.

We have previously described several receptors on the chondrocyte membrane. In an attempt to further characterize the coupling mechanisms of serotoninergic receptors, here we examined the involvement of serotonin in the phospholipase A2 activity. Serotonin dose-dependently stimulated phospholipase A2. This activation enhanced collagenase type II activity and had no effect on proteoglycanase activity.

Aged↗
PubMed1991

In vitro effect of nonsteroidal antiinflammatory drugs on proteoglycanase and collagenase activity in human osteoarthritic cartilage.

The effects of several nonsteroidal antiinflammatory drugs, used at concentrations achievable in synovial fluid, on human osteoarthritic (OA) cartilage metallo-protease activity in vitro was studied. Acetaminophen and ketoprofen had no effect; sodium salicylate, indomethacin, and diclofenac slightly decreased proteoglycanase activity. Piroxicam and tenoxicam suppressed proteoglycanase activity by 48.2% and 68.3%, respectively, and suppressed collagenase activity by 19.1% and 36.8%, respectively. Use of these NSAIDs may help to decrease cartilage catabolism in patients with OA.

Acetaminophen↗
PubMed1991

Plasma fibronectin and complement following infusion of colloidal solutions after spinal anaesthesia.

A randomized study of 30 patients undergoing uncomplicated surgery under spinal anesthesia was conducted to assess the influence of colloids on the kinetics of plasma fibronectin and complement. Both are opsonins of the reticuloendothelial system; moreover fibronectin is concerned with host resistance against septic complications following trauma and surgery. The patients were assigned to receive either Ringer's lactate (Group 1), gelatin (Group 2) or dextran 40 (Group 3). Blood samples were withdrawn before colloids or Ringer's infusion and during the 4 postoperative days. There was a reduction in plasma fibronectin throughout the study in groups 1 and 3, but an increase in group 2 by 24 h. The adhesion of plasma fibronectin to gelatin was maximal 1 h after infusion (44%) and remained significant up to day 2 in group 2. There was no relationship in groups 1 and 3. C3 and C4 components of complement exhibited a low value in the early post-operative period, due to hemodilution. This study shows an in vivo fibronectin-gelatin interaction, and suggests that gelatin infusion inhibits the increased shift of plasma fibronectin at the site of tissue injury after surgery.

Adult↗
PubMed1991

The ability of suramin to block CD4-gp120 binding is reversed in the presence of albumin.

We have shown that suramin can directly inhibit the binding of the human immunodeficiency virus type 1 gp120 envelope protein to immobilized CD4, thus helping to explain the previously described antiviral properties of suramin. However, physiological concentrations of serum albumin significantly attenuated suramin's antiviral effects, suggesting that only free suramin has antiviral properties. Reported discrepancies between in vitro and clinical activities of suramin may be due to differences between free suramin levels in experimental assays and those achievable clinically.

Animals↗
PubMed1991

[Serum hyaluronic acid and phospholipase A2 in an arthritic population].

Serum hyaluronic acid (HA) and A2 phospholipase (A2PL) activity were measured by radioimmunoassay (Pharmacia) and using a specific phospholipid substrate respectively, as potential markers of osteoarthritic synovitis. With neither age, treatment nor sample time taken into consideration, the concentration of HA (micrograms/ml) was 585 +/- 1,054 in rheumatoid arthritis, 379 +/- 409 in knee osteoarthrosis, 272 +/- 384 in hip osteoarthrosis, 131 +/- 144 in low back pain and 44 +/- 23 in osteoporosis, with no significant difference between the groups. HA was nevertheless found to be significantly higher in knee osteoarthrosis patients than in normal controls, when samples were drawn at the same time of day. Physical exercise (pedalling), as well as 20 hours lying flat and an intra-articular injection of corticosteroids did not cause any significant variation in serum HA levels in knee osteoarthrosis patients, in contrast to 20 hours of rest in the controls. A2PL activity was significantly higher in osteoarthrosis patients than in the controls, decreased with rest and corticosteroids and was not dependent upon sample time.

Aged↗
PubMed1991

Study of an inhibitor of plasminogen activator (tranexamic acid) in the treatment of experimental osteoarthritis.

The effects of tranexamic acid, an inhibitor of plasminogen activator, were evaluated in a rabbit model of osteoarthritis induced by section of the knee joint anterior cruciate ligament. Prophylactic treatment administered intramuscularly thrice weekly for 12 or 24 weeks significantly reduced cartilage destructive lesions, increased cartilage hypertrophy but did not prevent changes in cartilage water and proteoglycan content. A suppression of synovial membrane stromelysin and collagenase activity was found while phospholipase A2 activity was unaffected.

Animals↗
PubMed1991

[Effects of naproxen (naprosyne) on the metabolism of arthrotic cartilage in man in vivo].

Degradative enzyme (proteoglycanase and collagenase) as well as proteoglycan synthesis enzyme (glycosyl-transferase) activity was studied in osteoarthritic fibrillated cartilage. Proteoglycanase activity was significantly lower in 10 patients with hip osteoarthritis treated with Naproxen (1 g/daily for 4 weeks) than in 10 patients treated with acetaminophen. Synthesis enzyme activity was similar in both groups. The results which confirm in vitro studies suggest that naproxen has not toxic effect on human osteoarthritic cartilage and could rather be beneficial.

Acetaminophen↗
PubMed1991

[Cytokines, prostaglandin E2, phospholipase A and metalloproteases in synovial fluid in osteoarthritis].

Concentrations of prostaglandin E2, interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha, phospholipase A2, collagenase and proteoglycanase activity were determined in synovial fluid from 26 patients with osteoarthrosis of the knee and 10 with rheumatoid arthritis. Osteoarthrosis synovial fluid was characterised by the absence of interleukin 1 beta while tumour necrosis factor alpha and interleukin 6 were present in relatively large amounts, by a very high phospholipase A2 activity contrasting with a very low concentration of prostaglandin E2, and by a collagenase/proteoglycanase activity only slightly less constant and high as in rheumatoid arthritis. In osteoarthrosis patients, the interleukin 6 concentration, but not that of tumor necrosis factor alpha, was correlated with the collagenase and proteoglycanase activity of synovial fluid.

Adult↗
PubMed1990

Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells.

The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma.

Affinity Labels↗