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Biomedical subjects

L Mackenzie

Publications and source records attributed to L Mackenzie.

34 records · Page 2Linked to original sources
PubMed1988

CD5-expressing B lymphocytes in the blood and salivary glands of patients with primary Sjögren's syndrome.

CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on a minute fraction of circulating B cells. The number of CD5 + B cells in the blood of patients with Sjögren's syndrome was slightly higher than in control blood, but it became statistically significant after treatment of the cells with phorbol myristic acetate. These numbers were even higher in patients with homogeneous serum bands than in the others. A few scattered cells were stained with anti-human IgM antibody on salivary gland sections, and among them 5-10% were found to be positive for anti-CD5.

Adult↗
PubMed1988

Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies.

A subset of B cells expressing the CD5 marker, a 67 KD molecule, has been implicated in the pathogenesis of autoimmune disease. To study the immunoglobulin repertoire of CD5+ B cells we investigated chronic lymphocytic leukemic (CLL) cells, since the majority of the malignant clones express CD5. CLL were induced to secrete their IgM in vitro by phorbol 12-myristate 13-acetate (PMA) and the supernatants screened for binding to a panel of autoantigens. Twelve out of 14 CLL clones were autoreactive, binding to Fc of IgG, ssDNA, dsDNA, histones, cardiolipin, or cytoskeletal components. Many also bound to more than one antigen tested for, showing multispecificity. Our data suggest that a high proportion of CD5+ B cells are programmed to secrete multispecific autoantibodies.

Antibodies, Neoplasm↗
PubMed1988

The importance of CD5-positive B cells in nonorgan-specific autoimmune diseases.

CD5, the human counterpart of Ly-1 molecules in the mouse, are detectable but weakly expressed on a minute fraction of circulating B cells. The number of CD5-expressing B cells is increased in patients with rheumatoid arthritis or primary Sjögren's syndrome. These cells are similar to those leading to chronic lymphocytic leukemia (they may be induced to produce multispecific autoantibodies). Multispecific autoantibodies have also been described in the early B cell repertoire.

Animals↗
PubMed1987

Reduced B-cell galactosyltransferase activity in rheumatoid arthritis.

Autosensitisation to IgG may be important in the pathogenesis of rheumatoid arthritis and could be related to reduced glycosylation of the oligosaccharides in the C gamma 2 region of serum IgG. The activity of galactosyltransferase, the enzyme that catalyses the addition of galactose to the oligosaccharide chains, was measured in the circulating B cells of seventeen patients with classic rheumatoid arthritis. It was significantly lower than that of a group of eleven controls (p less than 0.001) or of nine age-matched controls (p less than 0.001). In contrast, the enzyme activity of the T cells was within the range of that in nine age-matched controls, and enzyme activity in monocyte-rich mononuclear-cell populations was higher than in controls, possibly reflecting stimulation of the monocytes in rheumatoid arthritis. These findings suggest that galactosyltransferase may regulate the degree of glycosylation during IgG synthesis and could therefore be implicated in the rheumatoid inflammatory process.

Adult↗
PubMed1987

Pharmacological modulation of photodynamic therapy with hematoporphyrin derivative and light.

The interactions between photodynamic therapy (PDT) with hemotoporphyrin derivative (HPD) and treatment with cytotoxic drugs have been examined using both an in vitro tissue culture assay and an in vivo transplantable mouse tumor assay. Adriamycin (0.5-4.0 mg/kg) administered with HPD and at the time of irradiation potentiated the photodynamic effect, doubling the duration of tumor control. Adriamycin administered after PDT was not as effective. Methotrexate (0.2 mg/kg) also potentiated the tumor response to PDT. The other cytotoxic agents tested, cyclophosphamide, thiotepa, vincristine, and 5-fluorouracil, did not result in significant increases in tumor responses at the doses tested. In contrast to the effects observed in vivo, Adriamycin inhibited the photodynamic destruction of Raji or Lewis lung carcinoma cells in vitro, in part by reducing the uptake of HPD. Methotrexate had no effect on either the uptake of HPD or the efficacy of photodynamic destruction of Raji cells in vitro. The discrepancy between the in vitro and in vivo results implies that the interaction between PDT and other pharmacological agents cannot be assessed in vitro.

Animals↗
PubMed1987

CD5 positive B cells in patients with rheumatoid arthritis: phorbol ester mediated enhancement of detection.

CD5 molecules present on human T cells are detectable but weakly expressed on some human B cells. We have increased the sensitivity of their detection by treating the B enriched cells with phorbol myristic acetate (PMA), a tumour promoting agent. The numbers of CD5+ B cells in the blood of patients with rheumatoid arthritis (RA) were higher than in control blood, and after PMA treatment this was statistically significant. CD5+ B cells were also increased in tonsils, lymph nodes, and spleens after PMA activation. There were no significant differences between the percentages of B cells carrying chi or lambda light chains in their expression of CD5 molecules in patients with RA.

Adult↗
PubMed1987

A cross-reactive idiotype on anti-DNA and lymphocytotoxic antibodies.

The possibility that shared idiotypes may be present on antibodies of different specificities was explored using sera from 13 patients with systemic lupus erythematosus. Eleven sera had anti-DNA and seven carried the 16/6 idiotype (ID). Two of the sera with 16/6 ID also had lymphocytotoxic antibodies, the activity of which was blocked by antibody to the 16/6 ID. Our studies reveal that 16/6 ID is present on two antibodies with different binding specificities.

Antibodies, Antinuclear↗
PubMed1986

[Expression of T-lymphocyte antigens by serum B lymphocytes in rheumatoid polyarthritis].

Molecules recognised by the monoclonal antibodies Leu 1 - OKT 1 - Mid 5 (CD5 molecules) were originally shown on human T cells and are equivalent to Lyt-1 molecules in the mouse. These surface molecules are detectable on some human B cells, but are weakly expressed. We have therefore tested the effects of the tumour-promoter, phorbol myristic acetate (PMA) on expression of these molecules on B cells. Sheep red blood cell rosette-depleted lymphoid organ or blood cells from 8 controls and 10 rheumatoid arthritis (RA) patients were examined fresh and cultured with PMA for 48 hours and the cells stained with Leu 1 or Mid 5 by indirect immunofluorescence. Cells were analysed by UV microscopy or flow cytometry. More RA blood B cells were positive for Leu 1 than normals before culture. Following incubation with PMA, the percentage of positive cells increased in all cell populations (1-49% in RA patients and 5-26% in controls). There was no difference in the expression of Leu 1 on Kappa--or lambda--positive cells before and after culture in PMA. Leu 1 positive cells were under-represented in Epstein-Barr virus-driven cell lines.

Adult↗
PubMed1985

Salsolinol and dopamine in rat medial basal hypothalamus after chronic ethanol exposure.

Endogenous levels of salsolinol and dopamine were measured by a gas chromatography/mass spectrometry (GC/MS) - selected ion monitoring technique using deuterated internal standards in Long Evans rats chronically exposed to ethanol for ten months. Chronic ethanol exposure produced significant increases of dopamine and salsolinol concentrations in the medial basal hypothalamus but not striatum. The data suggest that the occurrence of salsolinol in rat brain tissue is a consequence of an in vivo Pictet-Spengler cyclization.

Alcoholism↗
PubMed1985

Potentiation of photodynamic therapy with haematoporphyrin derivatives by glucocorticoids.

The effect of glucocorticoids on tumour destruction by photodynamic therapy (PDT) with haematoporphyrin derivative (HPD) and light has been examined in a transplantable mouse tumour model. Administration of glucocorticoid after irradiation enhanced the effect of PDT on both Lewis lung carcinoma and B16 melanoma. Administration of methylprednisolone acetate in depot form concurrently with HPD inhibited the response to PDT while soluble hydrocortisone sodium succinate had no effect. Correctly timed administration of glucocorticoid may have a place in treatment of human tumours by PDT with HPD. Glucocorticoid did not reduce the temporary photosensitivity of the skin induced by HPD.

Animals↗
PubMed1984

Resistance of schedule-induced behaviours to hippocampal lesions.

It has been reported that electrolytic lesions of the hippocampus accelerate the onset of schedule-induced drinking (SID) and also lead to significant increases in adrenal weights [2]. In the present experiment three groups of Long Evans rats received electrolytic or 6-Hydroxydopamine or sham lesions of the hippocampus and one group received electrolytic cortical lesions. Half of each group were tested 1 hr/day for 10 days under scheduled food delivery and the other half received food in a single presentation. It was found that both electrolytic hippocampal and cortical lesions reduced the level of SID compared with sham and 6-Hydroxydopamine lesions which did not differ from each other. However, there is support for the suggestion that hippocampal catecholamine neurones are involved in corticosterone regulation as shown by a significant increase in plasma corticosterone levels in non-scheduled, 6-Hydroxydopamine lesioned rats.

Animals↗
PubMed1983

Isolation of cell cycle-dependent gamma ray-sensitive Chinese hamster ovary cell.

A technique for the isolation of gamma ray-sensitive Chinese hamster ovary (CHO) cell mutants is described, which uses nylon cloth replica plating and photography with dark-field illumination to directly monitor colonies for growth after gamma irradiation. Two gamma ray-sensitive mutants were isolated using this method. One of these cells (XR-1) had a two-slope survival curve: an initial steep slope and then a flattening of the curve at about 10% survival. Subsequently, it was found that this cell is sensitive to gamma irradiation in G1, early S, and late G2 phases of the cell cycle, whereas in the resistant phase (late S phase) its survival approaches that of the parental cells. The D37 in the sensitive G1 period is approximately 30 rads, compared with 300 rads of the parental cell. This mutant cell is also sensitive to killing by the DNA breaking agent, bleomycin, but is relatively insensitive to UV light and ethyl methane sulfonate, suggesting that the defect is specific for agents that produce DNA strand breakage.

Animals↗
PubMed1981

Elusive allowances.

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Attitude to Health↗