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Biomedical subjects

P Dore-Duffy

Publications and source records attributed to P Dore-Duffy.

At least 37 records · Page 2Linked to original sources
PubMed1991

Cerebrospinal fluid eicosanoid levels: endogenous PGD2 and LTC4 synthesis by antigen-presenting cells that migrate to the central nervous system.

We analyzed CSF from patients with multiple sclerosis, patients with other neurologic diseases, and healthy controls for the presence of prostaglandin (PG) E2, F2 alpha, D2, I, A, and leukotriene (LT) C4. Control CSF had little measurable PGs or LTs. CSF eicosanoids from patients with progressive MS were increased. We found PGD2 only in MS CSF. CSF monocytes from patients in active disease produced significantly increased PGD, PGE, and LTC4 than paired peripheral blood monocytes and monocytes from healthy controls. We saw no significant difference in LTC4 production between MS and control peripheral blood monocytes.

Antigen-Presenting Cells↗
PubMed1989

Essential fatty acid and lipid profiles in plasma and erythrocytes in patients with multiple sclerosis.

This study was conducted to investigate the possible differences in erythrocyte lipid composition, which might account for the previously reported increase in erythrocyte membrane zinc levels in patients with multiple sclerosis (MS). Compared with healthy control subjects, plasma lipids in patients with MS contained less sphingomyelin but more phosphatidylserine and the cholesterol-phospholipid ratio was 42% higher in the plasma from MS patients (p less than 0.01). In erythrocytes from MS patients, phosphatidylinositol was lower and erythrocyte cholesterol per milligram protein was significantly lower than concentrations in healthy control subjects (p less than 0.01). Among the long-chain fatty acids, the omega-3 fatty acids were lower in plasma from MS patients and linoleic acid was lower in erythrocyte ghosts from MS patients (p less than 0.01). We conclude that altered levels of cholesterol in plasma and erythrocytes from MS patients may contribute to increased erythrocyte-membrane Zn in MS patients. It cannot be stated with certainty whether the altered fatty acid profiles in MS patients were a function of the disease or of altered fatty acid intake.

Cholesterol↗
PubMed1988

Synthesis of prostaglandin E by peritoneal macrophages from NZB/W mice.

Peritoneal macrophages from NZB/W (murine lupus) mice spontaneously produce less prostaglandin E (PGE) than peritoneal macrophages from immunologically normal mice. Reduced PGE synthesis is seen as early as 2 months of age and becomes more profound as disease progresses. It is suggested that impaired production of PGE by peritoneal macrophages from NZB/W mice may account in part for abnormal macrophage function observed in these animals.

Age Factors↗
PubMed1987

Age-related differences in lymphocyte adherence to myelinated tissue in multiple sclerosis.

Human peripheral blood lymphocytes were obtained from patients with MS and from healthy controls. Comparisons were made between the adherence of lymphocytes from donors of varying ages to myelin from donors of different age groups at the time of death. The adherence of control lymphocytes was maximum with lymphocytes from donors in their 30s. No obvious maximum for lymphocyte age was found for adherence of MS lymphocytes. However, MS adherence levels were significantly higher than control levels at most ages tested. Maximum adherence levels were observed for both MS and control cells with myelin from donors who were 20 to 45 years of age at the time of death. No significant difference between MS and control adherence to myelin from elderly donors was observed. Possible age-related changes in myelin and the relationship of maximum adherence to the peak age of onset of MS discussed.

Adolescent↗
PubMed1986

Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane-bound zinc in erythrocytes from patients with multiple sclerosis.

Previous studies have shown that zinc levels in erythrocytes are significantly elevated in patients with multiple sclerosis (MS). To examine the correlation between erythrocyte Zn levels and disease activity, we measured erythrocyte Zn levels longitudinally. Levels were dramatically decreased during a clinically documented exacerbation of MS. To determine the localization of increased Zn levels in MS erythrocytes, we employed standard techniques for the isolation of nonhemoglobin erythrocyte membrane ghosts. Patients with MS had three times more Zn in ghost material than did controls. Chloroform-methanol extraction in erythrocyte ghosts followed by determination of Zn levels indicated that most of the membrane-bound Zn was associated with the lipid-soluble fraction. Non-lipid-associated Zn and total membrane protein concentration were similar in MS and control samples. Results suggest that mechanisms which govern cellular availability, compartmentalization of Zn, or the binding of Zn to cell surface membranes may be altered in patients with MS, and that these mechanisms vary with disease activity.

Adult↗
PubMed1986

Lymphocyte adherence in multiple sclerosis: role of the cytoskeleton and prostaglandin E.

Human peripheral blood lymphocytes from patients with multiple sclerosis (MS) form significantly greater numbers of rosettes with virus infected cells than healthy controls. Because increased lymphocyte adherence in MS may be important to the disease process, we have investigated the mechanisms governing lymphocyte adherence in healthy control volunteers. We have previously shown that prostaglandins E1, E2 (PGE2), and dibutyryl cyclic AMP (db cAMP) and colchicine increase control lymphocyte adherence in healthy control volunteers. Colchicine treatment enhances PGE synthesis in control cells. We now report that colchicine (10(-5) + 10(-7) M) treatment of mononuclear cells does not enhance PGE synthesis in cells from patients with multiple sclerosis. Colchicine treatment did not affect MS lymphocyte adherence.

Aspirin↗
PubMed1986

Lymphocyte adherence to myelinated tissue in multiple sclerosis: correlation with disease activity.

Human peripheral blood T-lymphocytes adhere to myelinated sections of human and nonhuman brain tissue. No lymphocyte adherence is seen to gray matter. Lymphocytes from patients with MS adhere more than control lymphocytes. Lymphocyte adherence in patients with stable MS and in healthy controls did not vary more than 15%. Lymphocyte adherence in MS patients was decreased significantly during exacerbation. Values rose to pre-exacerbation levels in remissions. Results suggest that T cells that adhere to myelin may migrate from the peripheral blood during exacerbation.

Cell Adhesion↗
PubMed1986

Prostaglandin release in multiple sclerosis: correlation with disease activity.

Release of prostaglandin E (PGE) was examined in leukocyte cultures from patients with definite MS who had had at least one recent exacerbation, others with chronic progressive or stable MS, and healthy controls. MS patients had higher baseline levels of PGE than did controls. Patients with active symptoms exhibited a sharp increase in PGE release early in or just before the onset of clinical symptoms. Levels dropped early in exacerbation immediately after the burst in PGE synthesis activity. Values gradually increased to control levels and then to preexacerbation levels. Similar rises and falls were not seen in stable MS. MS patients may have a circulating population of activated leukocytes that produce PGE.

Acute Disease↗
PubMed1986

Serum 13-14-diOH-15-keto-prostaglandin F2 alpha and airway response to meclofenamate and metaproterenol in relation to the menstrual cycle.

In order to evaluate whether adverse reactions to a nonsteroidal antiinflammatory agent (NSAIA) were related to variations in prostaglandin levels during the menstrual cycle, we measured 13-14-diOH-15-keto-prostaglandin F2 alpha in serum and the effect on airways of a single dose of 100 mg oral meclofenamate and 1.5 mg inhaled metaproterenol during the early (follicular phase) and late (luteal phase) menstrual cycle. Among 24 women with premenstrual asthma (PMA), four women with regular asthma (REA), and four healthy women, the 13-14-diOH-15-keto-PGF2 alpha averaged 140.9 +/- 68.4 pg/0.1 ml during the follicular phase but only 14.4 +/- 2.2 pg/0.1 ml during the luteal phase (p less than 0.0001). Acute asthma reactions to the meclofenamate occurred during the follicular phase in six women with PMA but were never observed during the luteal phase (p = 0.016). These reactions occurred preferentially in patients on corticosteroids (p = 0.004). Conversely, one patient with PMA had 18% improvement in FEV1 with meclofenamate during the luteal phase. A placebo-controlled, double-blind evaluation of the healthy women and the women with REA revealed a trend toward improvement in FEV1 during the luteal phase (0.15 less than p less than 0.10) but no change during the follicular phase. The effect of metaproterenol did not vary with the menstrual cycle, and there was no interaction between the effects of meclofenamate and those of metaproterenol. It appears that meclofenamate causes adverse effects on pulmonary function in asthmatic women primarily during the follicular phase of the menstrual cycle. This effect is associated with corticosteroid treatment and may be related to monthly variation in serum 13-14-diOH-15-keto-PGF2 alpha.

Adult↗
PubMed1984

Generation of phenotypic helper/inducer and suppressor/cytotoxic T-cell lines from cerebrospinal fluid in multiple sclerosis.

The investigation of cell-mediated events in man has been largely limited to the study of the cells in the peripheral circulation. The study of T cells from localized anatomic compartments has been difficult due to the small numbers of cells usually obtainable from these sites. Investigation of such compartmentalized responses theoretically may yield information relating to both normal immunoregulation and autoimmune diseases--information that may not be obtainable through the investigation of the circulating cellular immune system. Utilizing cerebrospinal fluid (CSF) lymphocytes from patients with multiple sclerosis as a model of compartmentalized immunologically relevant cells, the technology for the generation of long-term T-cell lines from compartments both in continuous culture and after cryopreservation and that consist of both helper/inducer and suppressor/cytotoxic phenotypes have been generated. The 10(4) to 10(5) CSF cells obtained initially from individual patients have often been expanded into greater than 10(8) total cells within 4 months. The ability to generate large, stable, cryopreservable helper and suppressor/cytotoxic T-cell lines from limited access compartments will allow for new investigative approaches into both normal immunoregulation and autoimmune diseases in man.

Antigens, Surface↗
PubMed1984

Quality-specific taste changes in multiple sclerosis.

Taste sensitivity in 79 patients with multiple sclerosis (MS) and 65 age- and sex-matched control subjects was measured with a sip-and-spit, suprathreshold scaling, magnitude estimation procedure using six concentrations each of sodium chloride, sucrose, citric acid, and quinine hydrochloride. Results were analyzed with a taste scoring system and by plotting psychophysical functions (log concentration versus log magnitude estimate) normalized to 1.0 M sucrose. Gender did not affect taste scores, but age was inversely related, so the results were analyzed by an analysis of covariance with age as the covariant. There was a significant alteration in taste sensitivity in the subjects with MS for sodium chloride and quinine hydrochloride stimuli but not for sucrose and citric acid; these results were confirmed by a separate analysis of the psychophysical functions. Some of the MS taste scores correlated with MS functional and physical disability scores. Taste sensitivity was not correlated with clinical history or presence of facial symptoms.

Humans↗
PubMed1984

Thiabendazole-induced suppression of renal damage in a murine model of autoimmune disease.

The present study was designed to compare the efficacy of thiabendazole (TBZ) with that of levamisole in the treatment of murine lupus. Both drugs were given in the presence of the T-dependent antigen dinitrofluorobenzene (DNFB). Female NZB/NZW F1 mice 2 months of age were treated with TBZ + DNFB, levamisole + DNFB, and drug solvents, once a week, from 2 through 9 months of age. All mice were then left without further treatment for an additional 2 months. TBZ/DNFB treatment has significantly reduced proteinuria, glomerular deposition of immunoglobulins and complement components, and development of the proliferative glomerulonephritis characteristic of untreated NZB/NZW mice. Levamisole/DNFB treatment, on the other hand, had little to no effect on the course of the disease when compared with untreated NZB/NZW mice. These studies clearly demonstrate the effectiveness of the TBZ/antigen therapy in maintaining renal function in autoimmune diseased mice.

Animals↗
PubMed1984

Oral administration of prostaglandin E2 to humans: effects on peripheral blood leukocyte function.

We examined the effect of small orally administered doses of prostaglandin E2 (0.5 and 1.0 mg) on human peripheral blood leukocyte function. Plasma levels of 13,14-dihydro-15-keto-prostaglandin E2 peaked at 1 hour and returned to baseline at 3 to 4 hours. Adherence of lymphocytes to virus-infected cells was increased significantly 5 hours after ingestion of prostaglandin E2. Increases in adherence were similar to those found when lymphocytes were incubated in vitro with 10(-10) mol/L prostaglandin E2. Thus, this cell-cell interaction is very sensitive to prostaglandin E. Orally administered doses of prostaglandin E2 had only marginal effects on other leukocyte functions (active and total E-rosette formation, lymphocyte proliferation response to mitogen, and monocyte natural cytotoxicity) that are far less sensitive to prostaglandin E in vitro. Prostaglandin E2 clearly has the capacity to influence lymphocyte function when administered orally to normal humans.

Administration, Oral↗
PubMed1983

Interferon-mediated inhibition of prostaglandin synthesis in human mononuclear leukocytes.

In this study, the question of whether human leukocyte-derived and fibroblast-derived interferon had an effect on prostaglandin metabolism in human peripheral blood mononuclear cells has been considered. Both leukocyte- and fibroblast-derived interferon were potent inhibitors of mononuclear cell prostaglandin synthesis at low physiological concentrations. Inhibition required a minimum incubation of 1 hr. Interferon had no effect on release of arachidonic acid; synthesis of hydroxy fatty acids was slightly increased.

Arachidonic Acid↗
PubMed1983

Lymphocyte adherence in multiple sclerosis: lack of virus specificity.

The virus specificity of adherence of peripheral blood mononuclear leukocytes from patients with multiple sclerosis and from age- and sex-matched healthy volunteers to tissue culture cells infected with measles virus, Newcastle disease virus, and vesicular stomatitis virus was studied. Lymphocyte adherence to uninfected cells is uniformly low (5-15% tissue culture cells with greater than 3 lymphocytes adhered). Adherence to cells infected with virus is enhanced 2- to 4-fold in controls and 2- to 10-fold in patients with multiple sclerosis. Virus-specific antigen, antiserum, and receptor, at least in part, inhibited adherence to all cells tested. It is concluded from these studies that increased lymphocyte adherence in multiple sclerosis is not measles virus specific.

Adult↗
PubMed1983

Zinc in multiple sclerosis.

Zinc profiles were examined in 68 patients with multiple sclerosis, 62 normal volunteers, and 13 patients with other neurological diseases. Plasma zinc levels were slightly increased in patients with multiple sclerosis and significantly increased in those with other neurological impairments (p less than 0.01), compared with control subjects. Albumin-bound as well as protein-bound zinc levels were normal in all groups tested. The alpha 2 macroglobulin-bound zinc level was significantly lower (p less than 0.01) in patients with multiple sclerosis than in control subjects. Erythrocyte-bound zinc levels were significantly increased (p less than 0.05) in patients with multiple sclerosis when compared with control subjects. Erythrocyte-bound zinc was normal in patients with other neurological impairments. Because erythrocyte-bound zinc levels are relatively independent of daily fluctuations in dietary zinc intake, an increase in these values may suggest alterations in the control mechanisms governing zinc compartmentalization in patients with multiple sclerosis.

Blood Proteins↗
PubMed1982

Antinuclear antibodies in multiple sclerosis.

Low levels of antinuclear antibodies (ANAs) were found by indirect immunofluorescence in the serum of patients with multiple sclerosis (MS). Antibodies were found in 22 (81%) of 27 patients with MS and four (20%) of 20 healthy control subjects, with human epithelial (HEp-2) cells as substrate. Antinuclear antibody titers ranged from 8 to 32 in patients with MS and rarely reached above 8 in control subjects. The most common fluorescence patterns produced by MS serums were diffuse, fine speckled, and diffuse with fine-speckled nuclear fluorescence. Large nucleolar speckles and cytoplasmic fine speckles were also seen. Similar, although stronger patterns were seen in control subjects with positive tests for systemic lupus erythematosus. No correlation was found between ANA and antimeasles antibody titers. The presence of a heterogeneous population of circulating antibodies to a variety of nuclear and cytoplasmic antigens lends further support to the concept that altered immune reactivity exists in MS.

Adult↗