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K S Barron

Publications and source records attributed to K S Barron.

31 records · Page 2Linked to original sources
PubMed1990

Naproxen-induced pseudoporphyria: a distinctive photodermatitis.

A distinctive photodermatitis developed in 22 children who had been receiving naproxen for prolonged periods. The eruption was marked by erythema, vesiculation, or increased skin fragility characterized by easy scarring of sun-exposed skin. Results of biochemical studies for porphyria were normal, and other causes of photosensitivity were believed to be unlikely. Of the 22 patients, 21 had juvenile rheumatoid arthritis; one patient had systemic lupus erythematosus. Twenty of the patients had fair skin and blue eyes. In each case, all findings except scarring resolved when naproxen was discontinued. Attention must be paid to complaints suggesting photosensitivity in children receiving naproxen.

Arthritis, Juvenile↗
PubMed1989

Kawasaki syndrome: still a fascinating enigma.

In the two decades since this condition was first recognized among Japanese schoolchildren, preventive measures to lower the incidence of coronary artery aneurysms and various cardiac sequelae have significantly reduced mortality. Although the etiology of Kawasaki syndrome remains poorly understood, new evidence points to an inherited defect in T-lymphocyte immunoregulation.

Aspirin↗
PubMed1989

Abnormalities of immunoregulation in juvenile rheumatoid arthritis.

Immunoregulatory imbalances are thought to be involved in the pathogenesis of juvenile rheumatoid arthritis (JRA). We have found that a subset of patients with JRA demonstrate a marked expansion of B cells without an alteration in B cell subset distribution. However, there was actually decreased in vitro immunoglobulin production in response to stimulation with either pokeweed mitogen or hydrocortisone. These B cell abnormalities were found to correlate with a marked increase in the percentage of CD4 + CD45R + T cells, a T cell subset thought to be responsible for inducing suppression. In addition, there was a significant decrease in the percentage of CD4 + CD29 + T cells, a T cell subset thought to be responsible for inducing B cell immunoglobulin production. Our results suggest that the B cell abnormalities seen in JRA may be related to defects in T cell immunoregulation.

Adolescent↗
PubMed1988

Modulation of a human lymphoblastoid B cell line by cyclic AMP. Ig secretion and phosphatidylcholine metabolism.

A transformed human B cell line, LA350, was found to be sensitive to cAMP-elevating agents by responding with rapid (0 to 2 h) severalfold elevations of intracellular cAMP to treatment with cholera toxin, isobutylmethylxanthine (IBMX), forskolin, and dibutyryl cAMP (all p less than 0.001). These cAMP-elevating agents also produced significant inhibitions of subsequent (48 to 72 h) Ig secretion by the same B cells as measured by a reverse hemolytic plaque assay and an enzyme-linked immunoadsorbent assay for IgM (both p less than 0.001). PMA- and IBMX-treated cells were particularly responsive to the effects of cholera toxin, showing a doubling of cAMP content and profound decrease in Ig production (p less than 0.001). Because our previous studies had correlated activation of the metabolic turnover of the phosphatidylcholine (PC) fraction of membrane phospholipids with enhanced Ig secretion, we examined the sensitivity of PC metabolism to cAMP in control and PMA-stimulated cells. Formation of PC was found to be inhibited by forskolin and IBMX (both p less than 0.002) but breakdown of PC was stimulated (p less than 0.001). These findings imply that as the enzymatic products of PC, choline phosphate and diacylglycerol, are depleted due to the combined effects of cAMP upon synthesis and turnover of PC, there is a decrease in Ig secretion. Since diacylglycerol activates protein kinase C, it appears reasonable that Ig secretion is at least partially regulated by cAMP-responsive alterations in PC metabolism produced by protein kinase C-induced phosphorylation. We conclude that the early cAMP-sensitive changes in PC metabolism in this activated B cell line may signal for subsequent alterations in Ig secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Spinal cord compression by epidural lipomatosis in juvenile rheumatoid arthritis.

Two cases of spinal cord compression secondary to steroid-induced epidural lipomatosis in systemic juvenile rheumatoid arthritis (JRA) patients are reported. This complication of prolonged corticosteroid therapy has not been described previously in children with JRA. Epidural lipomatosis should be considered in the differential diagnosis of JRA patients receiving high-dose and/or prolonged corticosteroid therapy who present with neurologic signs and symptoms referable to the spinal cord.

Adrenal Cortex Hormones↗
PubMed1988

HLA-B27-associated arthropathy in childhood: long-term clinical and diagnostic outcome.

We conducted HLA-B27 tissue typing assessments on 430 consecutive children whose main symptom at presentation to our clinic was arthritis/arthralgia. Eighty-five of them (20%) had the B27 antigen. Thirty-six of these children were reexamined after a mean followup period of 8.9 years. Although most had definable rheumatic diseases, only 2 met the New York criteria for ankylosing spondylitis (AS). Children with HLA-B27 and arthritis/arthralgia, although at increased risk of developing AS, have diverse diagnostic and clinical outcomes. The AS criteria used to diagnose the disease in adults may not be appropriate for use in children.

Arthritis, Juvenile↗
PubMed1988

Phorbol ester binding to a human lymphoblastoid B-cell line, LA350, stimulates 32P incorporation into selected phospholipids and immunoglobulin secretion.

Anti-mu antibody binds to surface IgM on LA350, a transformed human B-cell line, and causes the immediate (5 min) hydrolysis of phosphatidylinositol (PI) into inositol 1,4,5-triphosphate (IP3) and diacylglycerol followed by a subsequent (48-72 hr) increase in immunoglobulin M (IgM) production. Phorbol myristate acetate (PMA) in a dose-dependent fashion inhibited completely the anti-mu-stimulated hydrolysis of PI and its resynthesis (PI cycle) from phosphatidic acid (PA) (P less than 0.001). Phorbol dibutyrate (PD), but not the inactive methyl ester derivative of PMA (PMA-ME), inhibited the anti-mu stimulation of the PI cycle (P less than 0.001). Conversely, PMA and PD, but not PMA-ME, stimulated in a dose-dependent fashion the metabolic events consistent with an activation of a putative phosphatidylcholine (PC) cycle. For example, at 10(-8) M PMA there was a 300% increase in the acute (1 hr) incorporation of [3H]choline into PC (P less than 0.001), a 680% increase in the acute (1 hr) incorporation of 32P into PC (P less than 0.001), but no net synthesis of PC as measured by the lack of PMA-stimulated incorporation of 32P into PC in LA350 prelabeled for 24 hr. Also in cells labeled to equilibrium with [3H]choline and in pulse-chase experiments we established that PMA produces a rapid incorporation of choline phosphate into PC and a rapid breakdown of PC, yielding choline metabolites released as choline itself into external medium surrounding the cell. Binding studies with [3H]PD demonstrated a dissociation constant of 20 mM and 5.3 x 10(5) total binding sites per cell. PMA was as effective as cold PD in inhibiting [3H]PD binding (P less than 0.001), but PMA-ME was ineffective. PMA and PD, but not PMA-ME, produced a similar dose-dependent (maximal at 10(-8) M) increase (300%) in immunoglobulin production as measured by either an ELISA assay or a reverse hemolytic plaque assay (P less than 0.001). Thus, activation of either the PI or the PC cycle results in significant enhancement in immunoglobulin production in LA350. Although PMA turns off the PI cycle, it turns on the PC cycle. A common mechanism to explain these findings might be the activation of protein kinase C, indirect via diacylglycerol release in the PI cycle stimulation by anti-mu and direct in the PC cycle stimulation by PMA by virtue of direct binding to protein kinase C.

B-Lymphocytes↗
PubMed1985

Multiparameter analysis of human lymphocyte subpopulations using flow cytometry.

This review has emphasized several recent advances in our understanding of human lymphocyte biology made possible by mAbs that recognize specific functional subpopulations of lymphocytes, coupled with multiparameter flow-cytometric analysis. In the last 3 years, both the T4+ and T8+ subsets of T cells have been further divided according to function and appearance of specific cell surface antigens. In addition, subpopulations of NK cells with different maturation states and B cells with distinct functional abilities have been discovered. Multiparameter flow-cytometric analysis of lymphocyte subpopulations can provide clues to the pathogenetic mechanisms of immune disorders, as has been demonstrated in AIDS patients and children with JRA. The use of multiparameter flow-cytometric analysis to study human immune responses in vitro has enabled a clearer understanding of the complex lymphoid interactions and, as we believe, may play an important role in the analysis of immune-associated disease processes.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Cytotoxic anti-T cell antibodies in children with juvenile rheumatoid arthritis.

The object of this investigation was to determine the prevalence of anti-T cell antibodies in 66 children with various connective tissue diseases. Anti-T cell antibodies were found in 43/44 juvenile rheumatoid arthritis (JRA) patients (mean cytotoxicity 15.0%) and in 10/10 children with systemic lupus erythematosus (mean cytotoxicity 20.0%), but in only 1/15 normal controls and in none of 12 children with other arthritides. There was no significant difference in mean percent cytotoxicity among the JRA subclasses. In the JRA patients, the percent cytotoxicity was positively correlated with the erythrocyte sedimentation rate (P = 0.01), but not with the presence or absence of rheumatoid factor, antinuclear antibodies, or immune complexes. The sera of 3 JRA patients repeatedly inhibited the stimulation of normal lymphocytes by mitogens and antigens by 47-99% (measured by the incorporation of 3H-thymidine into DNA) when added to the culture system in the first 24 hours; normal sera did not. Sera from patients with JRA have increased reactivity with mitogen-activated lymphocytes and T cells compared with unstimulated cells as determined by flow cytometry. The expression of the "JRA antigen" requires protein synthesis but not DNA synthesis or cell division. We conclude that the majority of patients with active JRA have cytotoxic anti-T cell antibodies and that in selected patients, these antibodies may play a role in regulation of the immune response.

Antibodies↗
PubMed1982

Pulse methylprednisolone therapy in diffuse proliferative lupus nephritis.

The prognosis of patients with diffuse proliferative lupus nephritis is generally poor, and the majority of patients with this lesion develop progressive deterioration in renal function. Intravenous "pulses" of methylprednisolone have been advocated for the treatment of severe nephritis. In this study, 15 patients with biopsy-proven diffuse proliferative lupus nephritis were treated with oral high-dose prednisone therapy, initially 2 mg/kg/day. They were compared with seven patients with similar renal pathology treated with six daily pulses of methylprednisolone (30 mg/kg/day, not to exceed 1 gm/day), followed by prednisone orally, initially 2 mg/kg/day. There were no deaths in either group and the side effects of therapy were similar in the two groups. Pretreatment GFRs for the pulse and high-dose groups were similar. There was a more rapid improvement in GFR following pulse therapy, but the long-term effects on renal function for the two modes of therapy were the same.

Administration, Oral↗
PubMedDate not supplied

Mitogens, superantigens, and nominal antigens elicit distinctive patterns of TCRB CDR3 diversity.

The third complementarity-determining region (CDR3) is the only nongermline-encoded hypervariable region of the T cell receptor beta (TCRB) chain, and it is the region that has been predicted to confer fine specificity of the TCR for peptide-MHC complexes. For this reason analysis of TCRB CDR3 heterogeneity may provide insight into immune mechanisms operative in infectious and autoimmune diseases. PBMC stimulated with either mitogen (PHA), superantigen (TSST-1), or nominal antigen (tetanus toxoid) have been compared with unstimulated PBMC using a two-dimensional approach. Analysis of the expressed TCRBV gene repertoire CDR3 length profile coupled with SSCP methodology enabled the discrimination of sequences with the same CDR3 length. For both freshly isolated and PHA stimulated PBMC, a normally distributed spectrum of CDR3 lengths (five or more products) was observed. These products differed by 3 bp (1 amino acid) due to the strict requirement for in-frame rearrangements in the CDR3 region of TCR. By contrast, tetanus toxoid stimulated PBMC had restricted profiles for most TCRBV families after as few as 7 days of incubation. The oligoclonal nature of samples showing CDR3 length restriction was revealed by SSCP analysis and confirmed by sequence determination. Superantigen stimulation resulted in unique patterns of diversity, which included polyclonal expansion of specific TCRBV families as well as oligoclonal expansion of most other TCRBV families. These data reveal complex yet distinct patterns of TCR diversity in response to different T cell activation stimuli.

Adult↗