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Biomedical subjects

J R Walker

Publications and source records attributed to J R Walker.

At least 145 records · Page 8Linked to original sources

An inhibitor of leucocyte movement in the plasma of patients with rheumatoid arthritis.

Plasma from patients with rheumatoid arthritis shows inhibitory activity towards the random and stimulated movement of human polymorphonuclear leucocytes and peripheral phagocytic monocytes in vitro. The inhibitory activity is heat-labile, not present in plasma from patients with noninflammatory diseases, and appears to exert its inhibitory effects by occupying sites on the cell cell membrane from where it may be removed by washing. It is suggested that this factor(s) is responsible for the diminished accumulation of polymorphonuclear leucocytes into skin chambers with occurs in patients with rheumatoid arthritis.

Arthritis, Rheumatoid↗

Migration of peritoneal polymorphonuclear leucocytes in the rat.

The migration of PMNs into inflammatory sites in the rat has been studied using elicited peritoneal cells. These cells exhibit normal random migration and phagocytosis in vitro but their chemotactic response towards activated serum is significantly reduced when compared to cells isolated from peripheral blood. When injected intravenously, peritoneal cells not only show a greatly diminished ability to accumulate in inflammatory exudates but also block the migration of peripheral PMNs. Thus while PMNs obtained from the peritoneum may be suitable for some studies, they are not representative of peripheral cells with respect to their ability to accumulate in inflammatory exudates due to implanted inert sponges.

Animals↗

Aspirin, salicylate and prostaglandins.

The effects of aspirin, salicylic acid and gentisic acid on the paw swellings in the arachidonic acid-potentiated and in the conventional carrageenan-induced oedema tests as well as on the content of prostaglandin-like activity and leucocyte migration in the exudate of inert implanted sponges in the rat have been studied. It is concluded that aspirin exerts two separate inhibitory effects on prostaglandin formation in vivo, a rapid action of the intact molecule on easily accessible tissues and a later action due to its metabolic conversion to salicylic acid. Salicylic acid inhibits prostaglandin biosynthesis in vivo as the salicylate ion itself and there is no formation of a subsequent 'active' metabolite.

Animals↗

Isolation and characterization of dnaX and dnaY temperature-sensitive mutants of Escherichia coli.

Escherichia coli mutants with temperature-sensitive (ts) mutations in dnaX and dnaY genes have been isolated. Based on transduction by phage P1, dnaX and Y have been mapped at minutes 10.4--10.5 and 12.1, respectively, in the sequence dnaX purE dnaY. Both dna Xts36 and Yts10 are recessive to wild-type alleles present on episomes. F13 carries both dnaX+ and Y+; the shorter F210 carries dnaY+, but not X+. Lambda tranducing phages that carry dnaX+ or Y+ have been isolated, and hybrid plasmids of Col E1 and E. coli DNA from the Clarke and Carbon (1976) collection also carry portions of the dnaX purE dnaY region. Results obtained with the lambda transducing phages and the hybrid plasmids suggest that dnaX is a different gene from the previously characterized dnaZ gene, which is also near minute 10.5--The dnaXts36 mutant, after a shift to 42 degrees, stopped DNA synthesis gradually, and the total amount of DNA increased two-fold. When this mutant was shifted to 44 degrees, the rate of DNA synthesis dropped immediately and the final increment of DNA was only 10% of the initial amount. Replicative DNA synthesis in toluene-treated cells was completely inhibited at 42 degrees and was partially inhibited even at 30 degrees.--When the dnaYts10 mutant was shifted to 42 degrees, DNA synthesis gradually stopped, and the amount of DNA increased 3.6-fold. At 44 degrees, residual DNA synthesis amounted to a two-fold increase. Replicative DNA synthesis in vitro in toluene-treated cells was inactivated after 20 minutes at 42 degrees or by "preincubation" of cells at 42 degrees before toluene treatment.--The dnaX and dnaY products probably function in polymerization of DNA, although participation also in initiation cannot be excluded.

Base Sequence↗

Somatic cell genetics of human interferon production in human-rodent cell hybrids.

Forty-two primary human-mouse cell hybrids, derived in two separate experiments, were treated with Newcastle disease virus (NDV): eight hybrids were found to produce human interferon and this was shown in every case to be predominantly of the fibroblast type. An extensive analysis was made in terms of karyotype and marker enzymes on all the eight hybrids producing interferon and also on five hybrids which did not produce interferon, five randomly selected hybrids and eleven subclones resistant to diphtheria toxin. The results suggest that, contrary to previous reports, a gene on chromosome 5 is not involved in production of human interferon. Its production was however correlated with the presence of chromosome 9 in the hybrids. Analyses of two sets of human-Chinese hamster hybrid subclones from two different crosses were also consistent with the assignment of a human interferon gene to chromosome 9.

Animals↗

Directed migration of circulating polymorphonuclear leucocytes in patients with rheumatoid arthritis: a defect in the plasma.

The migration of peripheral polymorphonuclear leucocytes (PMNs) of patients with rheumatoid arthritis has been studied both in vivo and in vitro. A significant reduction in the accumulation of PMNs in skin chambers in patients with rheumatoid arthritis compared to controls was observed but no defect in cell movement was detected when the isolated PMNs from the patients were exposed to activated control plasma. However, when PMNs from the control group were tested against activated plasma from patients with rheumatoid arthritis there was a significant decrease in their chemotactic response. It is proposed that there is a humoral defect in the plasma of the patients.

Adult↗

Abnormal polymorphonuclear leucocyte chemotaxis in Behçet's syndrome.

Experiments both in vitro and in vivo have been performed to study the chemotactic response of polymorphonuclear leucocytes (PMNs) in Behçet's syndrome. The experimental results were apparently contradictory. Using modified Boyden chambers we found that the PMNs from patients with Behçet's syndrome responded to a greater extent in vitro than normal cells, but with skin chambers placed over abrasions the in vivo response was less than normal. The significance of these findings is discussed and related to the histological appearances that may be seen in this condition.

Adult↗

A comparison of two in vitro methods for studying a defect in leucocyte movement in rheumatoid arthritis.

Filter and agarose plate techniques have been used to study an abnormality of polymorphonuclear leucocyte movement in patients with rheumatoid arthritis. The chemotactic response of normal cells towards activated rheumatoid plasma was significantly less than that towards activated control plasma when examined in Boyden chambers. This defect was not observed using the agarose plate method where the response of both control and rheumatoid cells towards activated rheumatoid plasma was identical. The existence of the plasma defect, which has been shown to be cell-directed, would not have been apparent had the agarose plate method been used alone. The choice of suitable in vitro methodologies for studying leucocyte movement in pathological conditions is therefore of some importance.

Arthritis, Rheumatoid↗

Complement activation by rat platelets: its significance to inflammation in the rat.

Generation of chemotactic activity in rat plasma or serum by aggregated rat platelets or by an extract of lysed platelets has been demonstrated. Chemotactic activity was not generated from serum either in the absence of an intact complement system or by platelet lysate pre-incubated with soya bean trypsin inhibitor. The significance of these observations is discussed in relation to some recent work on the role of platelets in inflammation.

Animals↗

Presence of displaced neural elements within rat cerebellar fissures.

Clusters of neural tissue have been observed within the cerebellar fissures of normal and experimentally treated albino rats and hooded rats, between the ages of 5 and 90 days. The observations of these intra-fissural clusters were made in conjunction with several series of experiments dealing with the effects of various treatments on cerebellar morphogenesis. More important is the fact that similar displaced clusters are present in normal, untreated animals. Clusters can show a considerable variation in size, ranging from a few closely packed cells, to clusters with many cells completely occupying the area between the two folial surfaces, The clusters consist of immature or mature granule cells, depending on the age. With increasing age a well-developed neuropil is seen with bundles of parallel fibers coursing among the granule cells, along with occasional Bergmann glial fibers, capillaries and pericytes. Synaptic contacts, possibly granule cells, are present within the cluster. The continued differentiation of the cells in the clusters is exemplified by the observation of a mossy fiber terminal at the base of a cluster. Connecting each cluster with the nearby parenchyma is a stalk consisting of granule cells, Bergmann glial fibers, and neurites. The basal lamina of the folial surface is interrrupted at this point. The presence of these clusters implies a failure of normal morphogenetic and migrational control mechanisms. Importantly, the cells of the clusters continue to differentiate and to make synaptic connections, despite their abnormal location.

Age Factors↗

PGI2: a potential mediator of inflammation.

PGI2, but not its metabolite 6oxoPGF1alpha, is equivalent in potency to PGE1 as a potentiator of carrageenan, histamine and bradykinin-induced rat paw oedemas. PGI2 must, therefore, be considered as a potential mediator of inflammatory processes.

Animals↗

Growth and transplantability of clonally related tumorigenic murine cell lines.

A malignant cell line derived from the s.c. inoculation of Adenovirus 12 into a CBA mouse has been isolated in vitro, cloned, and within 10 passages the clones have been investigated for their karyotype, morphology, growth rate, saturation density and response to plant lectin in vitro, and their tumorigenicity and growth rate in vivo. The cell lines rapidly acquired a highly heterogeneous karyotype, but remained homogeneous with respect to more complex physiological parameters. Examination of the cellular characteristics has indicated that the rate of growth of the cell lines in vivo, but not their tumorigenicity, may be related to their in vitro potentials. The clones responded differently to the cytotoxic effects of concanavalin A, but there was no correlation between the effect of the lectin and the malignant potential of the cells.

Animals↗

The effects of D-pencillamine and levamisole on leucocyte chemotaxis in the rat.

The administration of D-penicillamine (25 mg/kg) or levamisole (5 mg/kg) had no effect on leucocyte emigration into the exudates formed in inert sponges implanted in normal rats. 2 In rats, previously sensitized to Bordetella pertussis and implanted with sponges containing pertussis vaccine, an increased leucocyte migration into the exudates occurred; this was significantly enhanced by the administration of the drugs. 3 Neither drug in vitro affected the chemotaxis of rat polymorphonuclear leucocytes although random migration was significantly increased by levamisole (2 microgram to 1 mg/ml). Neither drug affected the chemotaxis of rat mononuclear cells although levamisole (25 microgram/ml) significantly increased that of human monocytes. 4 It is concluded that both drugs produce similar effects in an animal model of delayed hypersensitivity and that their clinical antirheumatic actions may have common elements.

Animals↗

Identification of the Escherichia coli cell division gene sep and organization of the cell division-cell envelope genes in the sep-mur-ftsA-envA cluster as determined with specialized transducing lambda bacteriophages.

From a lysogen with lambda integrated in the leu operon, specialized transducing phages that carry the cell division, murein biosynthesis, and envelope permeability genes located about 0.5 min to the right of leu were isolated. These phages were used to identify the previously undiscovered cell division gene sep. A genetic map proves that sep is located in the sequence leuA sep murE murF murC ddl ftsA envA. A physical map of this region was prepared by heteroduplex analysis of the phage DNAs. Overlapping segments of host DNA extended rightward for as much as 26.4 kilobase pairs from the prophage insertion point (thought to be in leuA) to include all the genes through envA.

Cell Division↗