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Biomedical subjects

D Lewis

Publications and source records attributed to D Lewis.

At least 271 records · Page 15Linked to original sources
PubMed1985

Hormone secretagogues increase cytosolic calcium by increasing cAMP in corticotropin-secreting cells.

Corticotropin (ACTH)-releasing factor, vasoactive intestinal peptide, and catecholamines--hormones that stimulate ACTH secretion and cAMP generation--increased cytosolic calcium in AtT-20 cells. The increase in intracellular calcium is presumably a consequence of the stimulated cAMP synthesis, since forskolin, an activator of the catalytic unit of adenylate cyclase, and the cAMP analog 8-bromoadenosine 3',5'-cyclic monophosphate (8Br-cAMP) also increased the cytosolic levels of this ion. Pretreatment with somatostatin, a neuropeptide that inhibits stimulation of the adenylate cyclase system and the secretion of ACTH blocked the increase of cytosolic calcium. The effect of 8Br-cAMP, which bypasses the cyclase, was not inhibited by somatostatin pretreatment. The source of the increased calcium appears to be mainly extracellular. This is indicated by the inability of the secretagogues to increase cytosolic calcium in a medium deprived of this ion or in the presence of blockers of voltage-gated calcium channels. The involvement of calcium channels in the calcium rise evoked by the secretagogues was supported by experiments using the whole-cell patch-clamp technique. In these experiments 8Br-cAMP increased voltage-dependent calcium currents. These results suggest the following chain of events in the receptor-mediated elevation of cytosolic calcium and the concomitant release of ACTH from AtT-20 cells: hormone-receptor binding----cAMP synthesis----protein kinase activation----calcium channel activation----increase in cytosolic calcium----many steps----ACTH release. Phorbol myristate acetate, a compound which does not stimulate cAMP generation but enhances the release of ACTH in AtT-20 cells, decreased the cytosolic calcium level.

Adrenocorticotropic Hormone↗
PubMed1985

Radio-isotopic joint scans in haemophilic arthritis.

The majority of severe haemophiliacs will develop a crippling arthritis consequent upon recurrent haemarthroses although the pathogenic mechanism remains unclear. We have carried out technetium-99 pertechnetate joint scans in the elbows, knees and ankles of 23 haemophilic patients and compared the isotope uptake of the 15 patients with clinical and radiological evidence of arthritis to that of eight patients without arthritis, to 13 age-matched healthy male controls, and to 10 age-matched males with active rheumatoid arthritis. Isotope uptake into the knee joints was significantly higher in haemophilic arthritis than in controls, haemophiliacs without arthritis, and patients with rheumatoid arthritis [median percentage uptake of administered technetium (Tc) dose X 10(3) in right knee = 9.4, 6.2, 6.4 and 6.6, respectively]: and the differences from haemophilic arthritis were all significant (p less than 0.01, Mann-Whitney U test). Similar differences were seen in the elbows and ankles. Increased Tc uptake correlated strongly with frequency of haemarthrosis, pain, synovitis, range of movement and radiological changes in knees and elbows, but poorly with the lesser changes seen in the ankles. These results would support the theory that haemophilic arthritis amongst the inflammatory arthropathies and that scanning is an appropriate technique for following progression of joint disease.

Ankle Joint↗
PubMed1985

Reduction of postischemic edema with hyperbaric oxygen.

In recent years, reports have shown positive effects of hyperbaric oxygen (HBO) treatment in posttraumatic circulatory insufficiency of the extremities. A tourniquet model for temporary ischemia was used to examine such treatment in rats. The circulation of the rat hindlimb was interrupted for 3 hours, while the contralateral uninjured leg served as control. There was a significant (p less than 0.001) postischemic edema in the tourniquet leg up to 48 hours after restoration of circulation. One group of animals received treatment with hyperbaric oxygen at 2.5 atmospheres absolute (ATA) for 45 minutes after release of the tourniquet. This significantly reduced (p less than 0.001) the postischemic edema, and the reduction persisted for 40 hours after the last treatment. It is concluded that hyperbaric oxygen reduces postischemic edema. Hyperbaric oxygen may therefore be useful as an adjuvant in the treatment of acute ischemic conditions when surgical repair alone fails or is not sufficient to reverse the ischemic process.

Animals↗
PubMed1985

Human fetal osteoclasts fail to express macrophage antigens.

A method for the isolation of osteoclasts from human fetal long bones in sufficient numbers for phenotypic studies has been devised. Using this technique we have studied the expression of cell surface antigens characteristic of mononuclear phagocytes and other haemopoietic cell types on fetal osteoclasts and compared their phenotype with mononuclear cells in the same preparations. We found that osteoclasts failed to express DrW(Ia) and 24 of 26 antigens (in 6 of 7 antigenic clusters) found on mononuclear phagocytes of the same developmental stage. This implies that osteoclasts represent the maturational end-stage of a cell lineage separate from that of conventional blood cells, and of mononuclear phagocytes in particular.

Antibodies, Monoclonal↗
PubMed1985

Monoclonal antibodies to osteoclastomas (giant cell bone tumors): definition of osteoclast-specific cellular antigens.

The cellular origin of the osteoclast, the major agent of bone resorption, remains controversial despite the demonstration that osteoclasts form by fusion of mononuclear cells that are ultimately derived from a bone marrow stem cell. One view is that they are the terminally differentiated progeny of mononuclear phagocytic cells. However, we have previously provided evidence, from functional and phenotypic studies of rodent and human osteoclasts, that raises the possibility that osteoclasts form a separate cell lineage from conventional hemopoietic cells and macrophages in particular. In an attempt to elucidate this question, we have used monoclonal antibody techniques to examine the relationship between osteoclasts and other bone marrow-derived cells. By using osteoclasts from osteoclastomas (giant cell tumors of bone) for immunizations, we have produced 11 mouse hybridomas secreting monoclonal antibodies reacting with osteoclasts in normal human fetal bone and a variety of neoplastic and non-neoplastic bone lesions. Eight antibodies in 4 reactivity sets have been shown to recognize membrane antigens, whereas a further 3 react with cytoplasmic determinants. In 7 there is no cross-reactivity with macrophages in a wide range of tissues, thus effectively differentiating between these two cell types. These antibodies will prove useful for the identification of osteoclasts in tissues and in the separation of their circulating precursors, thus allowing an experimental approach to be made to many of the outstanding questions regarding the developmental pathobiology of the osteoclast.

Antibodies, Monoclonal↗
PubMed1984

Interdependence of H+, Ca2+, and Pi (or vanadate) sites in sarcoplasmic reticulum ATPase.

The phosphorylation of sarcoplasmic reticulum ATPase with Pi in the absence of Ca2+ was studied by equilibrium and kinetic experimentation. The combination of these measurements was then subjected to analysis without assumptions on the stoichiometry of the reactive sites. The analysis indicates that the species undergoing covalent interaction is the tertiary complex E X Pi X Mg formed by independent interaction of the two ligands with the enzyme. The binding constant of Pi or Mg2+ to either free or partially associated enzyme is approximately equal to 10(2) M-1, and no significant synergistic effect is produced by one ligand on the binding of the other; the equilibrium constant (Keq) for the covalent reaction E X Pi X Mg E-P X Mg is approximately equal to 16, with kphosph = 53 s-1, and khyd = 3-4 s-1 (25 degrees C, pH 6.0, no K+). The phosphorylation reaction of sarcoplasmic reticulum ATPase with Pi is highly H+ dependent. Such a pH dependence involves the affinity of enzyme for different ionization states of Pi, as well as protonation of two protein residues per enzyme unit in order to obtain optimal phosphorylation. The experimental data can then be fitted satisfactorily assuming pK values of 5.7 and 8.5 for the two residues in the nonphosphorylated enzyme (changing to 7.7 for one of the two residues, following phosphorylation) and values of 50.0 and 0.58 for the equilibrium constants of the H2(E X HPO4) in equilibrium with H(E-PO3) + H2O and H(E X HPO4) in equilibrium with E-PO3 + H2O reactions, respectively. In addition to the interdependence of H+ and phosphorylation sites, an interdependence of Ca2+ and phosphorylation sites is revealed by total inhibition of the Pi reaction when two high affinity calcium sites per enzyme unit are occupied by calcium. Conversely, occupancy of the phosphate site by vanadate (a stable transition state analogue of phosphate) inhibits high affinity calcium binding. The known binding competition between the two cations and their opposite effects on the phosphorylation reaction suggest that interdependence of phosphorylation site, H+ sites, and Ca2+ sites is a basic mechanistic feature of enzyme catalysis and cation transport.

Adenosine Triphosphatases↗
PubMed1984

Cell surface characterization of the human osteoclast: phenotypic relationship to other bone marrow-derived cell types.

Among the differentiated progeny of stem cells transplantable by bone marrow are osteoclasts, the multinucleate cells which are the major agents of bone resorption. Although the osteoclast is well characterized from a structural and functional standpoint, its development and origin are still far from clear. We have used monoclonal antibodies to investigate the interrelationship between osteoclasts and other haemopoietic cells in man. We have analysed the distribution of 19 granulocyte-monocyte antigens in eight reactivity clusters on the non-neoplastic osteoclasts present within nine osteoclastomas (syn. giant cell tumours of bone) and a single example of aneurysmal bone cyst. We found that osteoclasts are antigenically effete, failing to express granulocyte-monocyte, common leucocyte or other haemopoietic determinants; the only monocyte antigens detected on osteoclasts are My-7 and two closely related specificities, MCS.2 and DüHL60.4, which are also expressed by tissues outside the haemopoietic system. Our findings, taken together with recent transplantation studies, cast further doubt on the view that osteoclasts are specialized bone-resorbing macrophage-derived giant cells, and support a hypothesis that they are the end product of fusion of a hitherto unidentified circulating mononuclear cell type, the preosteoclast, which constitutes a cell lineage separate from those originating from the conventional multipotential haemopoietic stem cell, although still of bone marrow origin.

Antibodies, Monoclonal↗
PubMed1984

Oral gold: a comparison with placebo and with intramuscular sodium aurothiomalate.

The therapeutic and toxic effects of the orally absorbed gold compound auranofin have been compared with placebo and parenterally administered sodium aurothiomalate (GST) in 90 patients with active rheumatoid arthritis over one year. At the end of this period 57% of patients on auranofin, 73% on GST and 0% on placebo remained on therapy. Toxicity caused discontinuation of therapy in 10% of patients on auranofin, 20% on GST and 7% on placebo. Lack of response to therapy led to withdrawal of 20% on auranofin, 0% on GST and 90% on placebo. Multiple clinical and biochemical assessments were performed during this study. Analysing them separately, and in the case of 6 of them grouped together in a disease activity index, the same trend is apparent throughout, namely that placebo has no effect on active inflammatory rheumatoid arthritis, and that both gold drugs are beneficial. GST has an earlier effect and tends to produce a greater change but after one year there was no significant difference between the 2 gold drugs for any parameter assessed. Gold levels in plasma or erythrocytes did not predict or correlate with either the development of toxicity or clinical efficacy. This study has demonstrated the second-line potential of auranofin which seems to be effective at gold concentrations in the blood below those observed with GST therapy. Toxicity limits the use of gold salts in RA. If the reduced incidence of adverse reaction with auranofin observed in this study is substantiated in larger numbers over prolonged periods, the use of gold at an earlier stage of disease may be facilitated.

Administration, Oral↗
PubMed1984

Self-report and heart rate responses to a stressful task.

Data were obtained from a risk task, the zipwire, in order to examine self-report and heart rate responses of males and females. Using this task, heart rate data demonstrated similar patterns to those found in earlier parachuting studies. ANOVAs demonstrated significant differences between sexes in self-report measures, but no significant differences in heart rate. In addition, examination of the relationships between heart rate and self-report showed a positive correlation for the women, while there was a negative correlation for the men.

Adolescent↗
PubMed1984

Provocative endocrine testing in recovered depressives.

Twenty-eight patients underwent a series of provocative endocrine tests an average of one year after their last admission for depression. Hypersecretion of cortisol, early escape of cortisol from dexamethasone suppression, diminished growth hormone response to insulin-induced hypoglycemia and altered thyrotropin response to thyrotropin-releasing hormone reported in acute primary depression were not observed after recovery. There were no differences in these measures after recovery between previous suppressors and nonsuppressors to dexamethasone. The cortisol response to insulin-induced hypoglycemia was less than expected in 6 of 16 recovered patients tested. There were significant differences in post-dexamethasone urinary free cortisol and in basal and early post-insulin serum cortisol levels between patients who had been suppressors and those who had been nonsuppressors to dexamethasone during acute depression. Further studies need to be done to substantiate these findings. These data indicate that hormone responses in recovered depressives are largely normal, suggesting that abnormalities during depression are "state" related phenomena.

Adolescent↗
PubMed1984

Corynebacterium ulcerans infection associated with untreated milk.

Infection with Corynebacterium ulcerans has been previously reported in association with cows' milk. Further evidence that the disease is a zoonosis is given in this report of infection in a consumer of untreated milk. The organism was isolated from a sample of milk, and from two cows in a herd of 93 Jersey cattle. One of the farm workers was a symptomless nasal carrier.

Adult↗
PubMed1984

Microvilli- and desmosome-associated bodies in Crohn's disease and other disorders in childhood: an ultrastructural abnormality of the small and large intestine.

Ultrastructural studies of the small and large intestine from children revealed five cases showing abnormal small electron-dense bodies within enterocytes and goblet cells. The characteristic features of the bodies were: (a) they occurred within microvilli and within the apical part of the cell cytoplasm; (b) they showed an association with the most apically located desmosomes of the epithelial cells; (c) in the microvilli they were present within protrusions of the membrane, suggesting that they may bud out of the cell; and (d) they were not membrane-bound within the cell but were found outside the cell as luminal, membrane-bound particles. These bodies occurred in two children with Crohn's disease and in three children having other gastrointestinal disorders. Similar electron-dense bodies which did not have all of the characteristics listed above were found in a sixth child who had Crohn's disease. These electron-dense bodies do not resemble any known inclusion of intestinal epithelium, nor do they resemble any previously described microorganism, although their apparent release from the cell by a process of budding is suggestive of a microbial identity. The occurrence of these bodies in childhood Crohn's disease suggests that they may be disease-related, but their precise nature and relevance to this or other gastrointestinal disorders remain unknown.

Adolescent↗
PubMed1984

HLA in two islands of French Polynesia.

The HLA-A, B, and C antigens of 243 individuals from two Polynesian islands, Maiao and Hiva Oa, have been characterized. 328 haplotypes were defined by family analysis. Most frequent antigens were A2, A11, Aw24, A26 , Aw34 ; Bw38, Bw39 , Bw48 , Bw55 , Bw56 , Bw60 ; Cwl, Cw3, and Cw4. Several other antigens were present at low frequency or were present on only one island. New variants of Bw22 and B40 were found. Despite an overall similarity in antigens of the two islands, the combination of HLA-A, B and C antigens on the haplotype were distinctive. Of 328 total haplotypes identified, 65 were unique. Thirteen of these (20%) were present on both islands. Twenty-eight (43%) were unique to Hiva Oa and 24 (37%) were unique to Maiao . Significant, positive linkage disequilibrium values (delta) for HLA-A, B and HLA-B, C antigens were also different for the two populations.

Alleles↗
PubMed1984

Transcutaneous electrical nerve stimulation in osteoarthrosis: a therapeutic alternative?

Thirty patients with chronic pain due to osteoarthrosis (OA) of the knee were enrolled in a randomised double-blind cross-over trial of self-administered transcutaneous electrical nerve stimulation (TENS) and placebo TENS. Medication was standardised to paracetamol tablets only. As measured on visual analogue scales for pain relief 46% of patients responded to active therapy and 43% to placebo. The length of pain relief during active therapy was significantly longer than that during placebo. At the end of the trial more patients wanted to continue using active TENS in preference to placebo or their original medication. Although most of the parameters observed favoured active TENS, it was not possible to establish its clear superiority over placebo, because the response rate to placebo TENS was high and sustained for at least 3 weeks. This trial suggests that a longer study is required to establish the role of TENS as a therapeutic agent in the treatment of the pain of chronic arthritis.

Acetaminophen↗
PubMed1984

Characteristics of spontaneously proliferating mononuclear cells in rheumatoid arthritis.

The phenomenon of increased spontaneous incorporation of 3H-thymidine (3H-TdR) into peripheral blood mononuclear cells in rheumatoid arthritis (RA) has been investigated. The activity was found to be short lived and affected less than 1% of cells. Using a Percoll density gradient we identified two populations of active cells. RA patients with active synovitis and increased 3H-TdR incorporation in the low density population of cells have higher overall 3H-TdR incorporation than normal controls and patients with inactive RA. The low density cell population is enriched for Ia+ cells. The data are consistent with raised spontaneous 3H-TdR incorporation being due to an in-vivo cell mediated immune response.

Arthritis, Rheumatoid↗