Search PubMed⌕ Search

Biomedical subjects

R G Russell

Publications and source records attributed to R G Russell.

At least 235 records · Page 13Linked to original sources
PubMed1983

Effect of aspirin on urinary excretion of 6-ketoprostaglandin F1 alpha.

1. We studied the effect of oral administration of acetylsalicylic acid (1200 mg/day for 3 days) on the urinary excretion of 6-ketoprostaglandin F1 alpha in normal human subjects as an index of prostacyclin production in vivo. 2. The concentrations and excretion rate in urine fell to 45% of pretreatment levels in 3 days, but returned to pretreatment values after 7 days. 3. These results suggest that production of prostacyclin in vivo is only partially inhibited by high doses of aspirin and that there are sites of production of prostacyclin which are protected from inhibition by aspirin and which contribute to urinary 6-ketoprostaglandin F1 alpha. The measurement of 6-ketoprostaglandin F1 alpha in urine may therefore be of only limited value as an index of the metabolism of vascular tissue in vivo.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

The use of dichloromethylene diphosphonate for the management of hypercalcaemia in multiple myeloma.

We have assessed the effects of the diphosphonate, dichloromethylene diphosphonate (Cl2MDP), in 19 patients with hypercalcaemia and increased bone resorption due to myeloma. Cl2MDP (800-3200 mg daily by mouth or 300 mg daily by intravenous infusion) decreased plasma calcium and biochemical indices of increased bone resorption in 16 of 19 patients. This effect persisted for the duration of treatment (up to 14 weeks). Prolonged treatment was associated with a progressive rise in serum alkaline phosphatase and only a transient fall in hydroxyproline suggesting the stimulation of bone repair. Since myeloma is associated with significant morbidity and mortality due to progressive bone loss, these results suggest that long-term treatment of myeloma with Cl2MDP is worthy of further study.

Aged↗
PubMed1983

Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes.

The ability of herpes simplex virus (HSV)-specific, cytotoxic T lymphocytes to mediate recovery of mice lethally infected with HSV was examined. Adoptive transfer of splenocytes from mice that had been primed in vivo with HSV and restimulated with HSV in vitro protected lethally infected normal and cyclophosphamide-immunosuppressed mice from death. In contrast, equal numbers of normal splenocytes or immune splenocytes cultured without antigen failed to mediate recovery. Recovery was also transferred by noncultured, primary immune splenocytes, although the protective efficacy of these cells was 10-fold less than when immune splenocytes restimulated in vitro were used. Treatment of the cells with anti-Thy 1 or anti-Lyt 2.1 plus complement before adoptive transfer abrogated recovery. No decrease in protection was seen when in vitro-restimulated splenocytes were treated with anti-Lyt 1.1 plus complement. Splenocytes expression natural killer activity also failed to effect recovery. The administration of hyperimmune anti-HSV antibody to normal, immunocompetent mice resulted in recovery, whereas no significant protection of immunosuppressed mice by anti-HSV was observed. When antibody was given concurrently with cultured immune splenocytes, the percentage of mice that recovered from infection was greater than that seen with either antibody or cultured immune splenocytes alone. These experiments demonstrate that Lyt 2-positive cells with cytotoxic activity generated by in vitro immunization can mediate recovery from lethal HSV infection, whereas, under the conditions chosen, Lyt 1-positive cells were unable to mediate recovery.

Animals↗
PubMed1983

Respiratory tract lesions from infectious laryngotracheitis virus of low virulence.

The pathogenicity of the A4557-5 strain of infectious laryngotracheitis virus for eight-week-old chickens was investigated by aerosol route of infection; chickens were necropsied five days after infection. The virus caused mild catarrhal tracheitis, peribronchial lymphoid infiltration, and focal lymphocytic infiltration in the lung and focal lymphocytic infiltration in the air sacs of some chickens. Chickens infected with this virus developed low levels of humoral antibody and were resistant to intratracheal challenge with the virulent V154 strain. By comparison, aerosol infection with a similar dose of virulent V154 strain caused severe necrotizing laryngotracheitis with marked suppurative bronchopneumonia and airsacculitis.

Animals↗
PubMed1983

Characterization of infectious laryngotracheitis viruses, antigenic comparison by kinetics of neutralization and immunization studies.

Five isolates of infectious laryngotracheitis virus were compared by pock formation on the chorioallantoic membrane of embryonated eggs, plaque size in chicken embryo kidney tissue culture, and antigenic relationship using reciprocal kinetics of neutralization. The A4557-5 strain of infectious laryngotracheitis virus, which causes mild respiratory disease, produced pocks with a zone of edema on the chorioallantoic membrane. A virulent virus (Virus 1), isolated from an outbreak of severe disease characterized by a diphtheritic laryngotracheitis, produced the largest plaques in chicken embryo kidney cell culture. Other virulent viruses (Viruses 2, 3 and V154) did not have unique growth characteristics when grown on the chorioallantoic membrane or in chicken embryo kidney cell culture. All viruses were closely related antigenically as shown by kinetics of neutralization but viruses 2 and 3 were not homogeneous with the other three viruses when neutralized by anti-V154 chicken serum. Following aerosol infection, chickens infected with the A4557-5 virus were immune to challenge with virulent V154 virus. However, in comparison to SA-2 virus, this virus was a less effective immunizing agent when administered by the vent or drinking water methods.

Animals↗
PubMed1982

Adenylate cyclase of human articular chondrocytes. Responsiveness to prostaglandins and other hormones.

Adenylate cyclase [ATP pyrophosphate lyase (cyclizing), EC 4.6.1.1] was shown to be present in cultured human articular chondrocytes. Optimal conditions of incubation time, protein and substrate concentrations and pH were determined in whole cell lysates. Maximal activity occurred at pH 8.5 with no decrease in activity up to pH 10.0. Adenylate cyclase activity of particulate membrane preparations was enhanced by the addition of crude cytosol preparations. The prostaglandins E1, E2, F1 alpha, F2 alpha, D2, B1, B2, A1 and A2, as well as adrenaline and isoprenaline, stimulated adenylate cyclase derived from either adult or foetal chondrocytes. No significant stimulation was observed in the presence of human calcitonin or glucagon. Bovine parathyroid hormone always significantly stimulated the adenylate cyclase derived from foetal chondrocytes, but not from adult chondrocytes. Preincubation of the chondrocytes in culture with indomethacin and with or without supernatant medium from cultured mononuclear cells increased the responsiveness of the adenylate cyclase to prostaglandin E1.

Adenylyl Cyclases↗
PubMed1982

Phosphoinositide metabolism in human blood platelets: effects of two types of divalent cation chelators.

Phospholipid metabolism was investigated in platelets in relation to secretion of 5-hydroxytryptamine. Both thrombin and the ionophore, A23187, induced secretion of 5-hydroxytryptamine and platelet aggregation accompanied by the specific breakdown of phosphatidyl inositol. The products detected corresponded to phosphatidic acid and a substance which co-chromatographed with polyphosphoinositides and lysophosphatidyl inositol. Thrombin-induced aggregation, secretion and phosphatidyl inositol metabolism were all prevented by EDTA, but only the secretory response was inhibited by the intracellular calcium chelator chlortetracycline (CTC). In contrast, A23187 induced turnover of phosphatidyl inositol in the presence of EDTA even though aggregation and secretion were prevented. All three responses to A23187 were inhibited by chlortetracycline. Thus, platelet aggregation, secretion and phospholipid metabolism can be dissociated by the use of two types of divalent cation chelators: EDTA and CTC. Furthermore, these findings suggest that thrombin and A23187 induce phosphoinositide metabolism by two distinct mechanisms.

Blood Platelets↗
PubMed1982

Measurement of intracellular inorganic phosphate in human blood red cells, leucocytes and platelets.

The measurement of Pi in red blood cells, leucocytes, platelets and plasma by this method is both highly selective and sensitive for Pi. Whereas the ratio of intracellular to extracellular Pi is less than 1 in red cells, it is about 4 in platelets and about 2 in leucocytes. In platelets, where there are storage granules, the nucleotide levels are higher than in red cells or leucocytes. Cell lysis by digitonin proved to be a reliable technique for the rapid and efficient separation of cytosol from the particulate fraction. The isolation of cytosol with minimal contamination by lysosomes, electron dense granules and mitochondrial matrix depended on the use of appropriate concentration of digitonin. There was a linear relationship between platelet number and digitonin concentration which induced leakage of 90% of the LDH. In platelets about half of the Pi and 50% of the total ATP + ADP were found in the particulate fractions. In leucocytes most of the Pi and the bulk of nucleotides are present in the cytosol. These findings indicate the presence of at least two pools of nucleotides in platelets and leucocytes, and suggests that the inorganic phosphate in cytosol is at a higher concentration than outside the cells, implying a concentration gradient across the plasma membrane.

Adenosine Diphosphate↗
PubMed1982

Messenger function of prostaglandins in cell to cell interactions and control of proteinase activity in the rheumatoid joint.

Destruction of joint structures in arthritis may result from failure of normal mechanisms controlling interactions among cells of the various tissues of the joint. Normal synovium in culture produces less prostaglandin E (PGE) and collagenase than rheumatoid. When rheumatoid synovium is dissociated into cells, the adherent cell cultures rapidly lose the ability to synthesize large amounts of PGE and collagenase and become indistinguishable from normal synovial cells. A mononuclear cell factor (MCF) derived from supernatant media of cultured human blood mononuclear cells and a 'synovial factor(s)' (SF) from cultures of either normal or rheumatoid synovial fragments both stimulate production of PGE and proteinase by cells derived from human synovium, cartilage and bone. The activities of factors which may be present in these stimulatory supernatants may be unmasked in vitro when they are removed from the normal control present in vivo. Normal synovium probably contains cells which, with the appropriate stimulus, may be recruited to participate in joint tissue degradation. Normal connective tissue turnover may also be controlled by a neutral metallo-proteinase inhibitor (TIMP), which is produced in considerable amounts by normal synovium, but which cannot be detected in cultures of rheumatoid synovium. While corticosteroids inhibit the production and action of MCF and SF, they stimulate production of TIMP by normal or rheumatoid synovial tissue in vitro and may contribute to the endogenous control mechanisms. PGE may also have a modulatory role in these cellular interactions.

Arthritis, Rheumatoid↗
PubMed1982

An estimate of the endogenous secretion rate of calcitonin in man.

1. The metabolic clearance rate (MCR) of human calcitonin was measured in 12 normal subjects and four patients with Paget's disease by the infusion of synthetic human calcitonin (15-40 microgram/h for 2-24 h), and in 10 additional patients with Paget's disease from the disappearance rate of immunoreactive calcitonin from plasma after the intravenous injection of large doses of synthetic human calcitonin (0.5-1.0 mg). 2. The estimated MCR during the infusion studies (range 531-1224 litres/day) was similar to that calculated from the disappearance of large doses of synthetic human calcitonin injected intravenously in patients with Paget's disease (mean = 1035 litres/day; range = 593-1408 litres/day). 3. An eightfold range in the basal values of plasma immunoreactive calcitonin, in spite of the presence of a relatively constant MCR, suggests that the variation in basal plasma calcitonin was due principally to variation in the endogenous secretion rate for calcitonin. 4. The results suggest that the endogenous secretion rate for calcitonin is low in normal subjects (mean 124 +/- SEM 24 microgram/day), and give a basis for selecting the doses of calcitonin which can be considered physiological.

Adolescent↗
PubMed1982

Ultrastructural features of the osteoclasts from Paget's disease of bone in relation to a viral aetiology.

The ultrastructure of the osteocytes, osteoblasts, osteoclasts, haemopoietic and other connective tissue cells was examined in 27 biopsies from 22 patients with Paget's disease of bone. Electron microscopy showed characteristic nuclear and cytoplasmic inclusions in the osteoclasts of all of the 25 biopsies exhibiting histological evidence of Paget's disease. Such inclusions were absent from all the other types examined. The intranuclear inclusions consisted of stacked rows or complex whorls of tubular filaments with an individual filament diameter of 12-15 nm, often arranged in a paracrystalline array. The frequency of occurrence of inclusions in the osteoclasts and their individual nuclei measured quantitatively in 18 of the biopsies was related to the histological severity of the disease process. The similarity of the observed inclusions to those of paramyxovirus inclusion bodies (particularly measles) support the hypothesis that Paget's disease is a slow virus infection.

Adult↗
PubMed1982

Long-term treatment of osteoporosis with 24,25 dihydroxycholecalciferol.

Five patients with involutional osteoporosis were treated with 24,25 dihydroxycholecalciferol (24,25-(OH)2D3) for 6 months, in doses sufficient to double plasma levels at that time. Dietary calcium absorption transiently improved by nearly 2 mmol Ca per day at 2 weeks, but this effect was lost by 6 months. The calcium and phosphate balances followed the trends in calcium absorption. Only twenty-five dihydroxyvitamin D levels changed little. Histomorphometric and kinetic indices of new bone formation and bone blood flow remained stable but there was an increase in urine hydroxyproline at 6 months, which was of borderline statistical significance. Treatment at this dosage of 24,25(OH)2D3, which increased plasma levels within the physiological range, conferred no measurable long-term benefit on our patients. Larger doses, or combination therapy, may warrant further clinical evaluation in osteoporosis.

24,25-Dihydroxyvitamin D 3↗
PubMed1982

Interactions in connective tissues involving monocyte/macrophages and control of production of proteinases and proteinase inhibitors.

Using human articular chondrocytes in monolayer culture as an experimental system, we have been studying mechanisms of control of production and activity of neutral proteases which degrade connective tissue matrices. Soluble factors from cultured human blood mononuclear cells (MCF) or synovial fragment cultures (SF) stimulate the production of collagenase and proteoglycanase by chondrocytes. Chondrocytes also release a collagenase inhibitor (mol. wt. 26-31,000), which is similar to the tissue inhibitor of metalloproteinases (TIMP) synthesized by cultured mammalian tissues and this is reduced in cultures exposed to MCF or SF. Retinol and dexamethasone partially inhibit the factor-stimulated collagenase, but increase the amount of inhibitor, restoring it to control levels in the presence of MCF or SF. The effects of these agents in cellular interactions in vitro will be discussed in relation to their possible roles in the control of connective tissue turnover in vivo.

Blood Proteins↗
PubMed1982

Stimulation of prostacyclin production from vascular endothelial cells by plasma, serum and platelets under normal and pathological conditions.

We have investigated the effects of plasma and serum from normal subjects on the production of prostacyclin (PGI2) by cultured porcine aortic vascular endothelial cells, measured by radioimmunoassay of its stable metabolite 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha). Both plasma and serum caused significant stimulation of the production of 6-keto PGF1 alpha over basal levels. Serum caused consistently greater stimulation than plasma from the same individual. Washed platelet suspensions were induced to aggregate using thrombin and the supernatants stimulated the production of 6-keto PGF1 alpha by cultured endothelial cells. Preliminary studies also show that a stimulatory factor is released from cultured human leucocytes. Serum from patients with systemic lupus erythematosus (SLE) and severe systemic sclerosis (SS), two connective tissue diseases with autoimmune features and vascular complications, showed significantly reduced levels of stimulation when compared with a control group.

Animals↗