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L G Rider

Publications and source records attributed to L G Rider.

35 records · Page 2Linked to original sources
PubMed1997

Classification and treatment of the juvenile idiopathic inflammatory myopathies.

This article reviews the current status of the classification and treatment of the juvenile idiopathic inflammatory myopathies. The intent of classification is to define homogeneous groups that share similar clinical features, disease courses, and responses to therapy. The classification scheme proposed includes clinicopathologic subsets, serologic subjects based on the presence of myositis-specific and myositis-associated autoantibodies, and environmental triggers of myositis. Juvenile dermatomyositis is the most common and widely recognized of these disorders. The second part reviews the history of treatment of juvenile dermatomyositis and discusses agents to consider for patients with refractory disease, unacceptable steroid toxicity, or poor prognostic factors.

Adolescent↗
PubMed1996

Activation of the mitogen-activated protein kinase cascade is suppressed by low concentrations of dexamethasone in mast cells.

Antigen stimulation of mast cells via the IgE receptor, Fc epsilon RI, results in recruitment of the cytosolic tyrosine kinases, Lyn and Syk, and the phosphorylation of proteins. We examined the effects of the glucocorticoid dexamethasone on these events in a cultured (RBL-2H3) mast cell line. Nanomolar concentrations of dexamethasone suppressed phosphorylation of proteins that were associated with the activation of the mitogen-activated protein (MAP) kinase/phospholipase A2 pathway without inhibiting initial events. For example, tyrosine phosphorylation of the subunits of Fc epsilon RI, Lyn, or Syk or of the Ras-guanine nucleotide exchange factor, Vav, was not suppressed in cells treated with up to 1 microM dexamethasone. In contrast, phosphorylation of Raf1, MEK1, p42mapk, and cytosolic phospholipase A2, as well as the associated increase in MAP kinase activity and release of arachidonic acid, were markedly inhibited in cells treated with as little as 10 nM dexamethasone--a concentration that only partially inhibited hydrolysis of inositol phospholipids or release of secretory granules. Prolonged exposure to dexamethasone also resulted in a partial decrease in expression of MEK1, p42mapk, and cytosolic phospholipase A2, which may contribute further to the effects of dexamethasone on this pathway. Activation of the MAP kinase/phospholipase A2 pathway by the calcium-mobilizing agent thapsigargin was similarly suppressed in dexamethasone-treated cells. These findings suggested that an early step in the pathway, possibly a step immediately before the activation of Raf1, was suppressed by low concentrations of dexamethasone.

Animals↗
PubMed1996

Assessment of disease activity and its sequelae in children and adults with myositis.

Validated, comprehensive measures for assessing disease activity and its irreversible sequelae, known as disease damage, have not been developed for the idiopathic inflammatory myopathies (IIM), thus limiting our capacity to assess individual patients and responses to therapies. This review summarizes current approaches for assessing disease activity and damage in the idiopathic inflammatory myopathies and speculates on possibly useful novel approaches for the future. Disease activity and damage indices that combine a number of these assessments are proposed for use in all therapeutic trials. Methods for assessing target organs of the idiopathic inflammatory myopathies will likely evolve as more sensitive and specific measures are developed that can distinguish active inflammation from the irreversible effects of disease.

Adult↗
PubMed1995

NIH conference. Myositis: immunologic contributions to understanding cause, pathogenesis, and therapy.

The myositis syndromes, the most common forms of which are polymyositis and dermatomyositis, are defined by idiopathic chronic inflammation in skeletal muscle. Although initially described more than a century ago, these diseases are so rare and heterogeneous that we have only a limited understanding of their causes and treatment. Recently, autoimmune responses to nuclear and cytoplasmic autoantigens that are unique to patients with myositis, the myositis-specific autoantibodies, have proved clinically useful in helping predict signs and symptoms of myositis, immunogenetics, responses to therapy, and prognosis. We summarize this new information on the variety and nature of these autoantibodies, their target epitopes, and their possible use in identifying causes, pathogenetic mechanisms, and better therapies for these increasingly recognized disorders.

Autoantibodies↗
PubMed1995

Cerebrospinal fluid analysis in children with seizures.

Cerebrospinal fluid (CSF) examinations of 212 children aged two to 24 months with idiopathic nonfebrile seizures, complex febrile seizures, or status epilepticus, who had a lumbar puncture within 24 hours of the convulsion, were reviewed to determine whether an idiopathic convulsion can result in CSF abnormalities. Children with complex febrile seizures had a median CSF white blood cell count of 1 cell/mm3 (range 0-19 cells/mm3) and a median CSF polymorphonuclear (PMN) cell count of 0 cells/mm3 (range 0-8 cells/mm3). The CSF white blood cell (WBC) count was elevated above the upper limit of normal of 5 cells/mm3 in 9.8% and the absolute number of polymorphonuclear cells was more than 0 cells/mm3 in 26.2% of the complex febrile seizure subjects. Values at the 95th percentile were calculated; a total of 8 WBC/mm,3 4 PMN/mm,3 protein of 73 mg/dl and glucose of 119 mg/dl determined the 95th percentile CSF values for the patients with complex febrile seizures. Patients with nonfebrile seizures or with status epilepticus had similar findings. We conclude that complex febrile, idiopathic nonfebrile convulsions or status epilepticus may affect CSF findings in children: CSF with > 20 WBC/mm3 or > 10 PMN/mm3 should not be attributed to seizures.

Cerebrospinal Fluid Proteins↗
PubMed1995

Laboratory evaluation of the inflammatory myopathies.

The laboratory plays an important role in the diagnosis, evaluation, and classification of the heterogeneous group of diseases known as the IIM, which are characterized by chronic muscle inflammation. Serial measurements of the levels of muscle-derived enzymes in serum are the traditional laboratory studies used to follow the clinical course of patients with IIM, although other laboratory tests can also be useful in assessing myositis disease activity. Several markers of immune system activation, including cytokines and lymphocyte markers, show promise as possibly more sensitive measures of myositis disease activity. Discovery of a unique group of MSAs over the past decade has provided an immunologic basis for defining relatively homogeneous subsets of patients who share similar clinical features, disease courses, and responses to therapy. Future investigations of novel immunologic activation markers, as well as the cloning and expression of target autoantigens of the MSAs, should allow better diagnostic assays, enhanced prognosis, and a better understanding of the pathogenesis of these disorders.

Autoantibodies↗
PubMed1994

The cDNAs encoding two forms of the LYN protein tyrosine kinase are expressed in rat mast cells and human myeloid cells.

Two isoforms of lck/yes-related novel (LYN) protein tyrosine kinase (PTK) appear to play a role in B-cell-IgM and FcERI receptor signaling. The cDNAs lynA and lynB encoding these two forms were isolated and sequenced; they were derived from rat mucosal mast cell and human myeloid cell lines. The nucleotide (nt) and deduced amino acid (aa) sequences share 94 and 97% identity between rat and mouse lyn, respectively, and 88 and 96% identity between rat and human lyn. In all three species, a region of 20 aa is uniformly inserted at an identical site and its sequence is highly conserved. This suggests an important regulatory role for this region mediated by this PTK.

Amino Acid Sequence↗
PubMed1994

A broadened spectrum of juvenile myositis. Myositis-specific autoantibodies in children.

OBJECTIVE: Myositis-specific autoantibodies (MSA) define relatively homogeneous clinical and immunogenetic patient groups in adults with idiopathic inflammatory myopathies (IIM). This study explores the usefulness of MSA in defining groups of children with myositis. METHODS: Sera from 77 children with myositis and other connective tissue diseases were tested for MSA by immunoprecipitation and immunodiffusion. Clinical data were collected and analyzed. RESULTS: The MSA anti-PL-12 (alanyl-transfer RNA synthetase), anti-Jo-1 (histidyl-tRNA synthetase), anti-signal recognition particle, and anti-Mi-2 were each identified in the sera of 12 children with IIM. In these patients, the clinical manifestations, disease courses, and responses to therapy closely resembled those in adults with the same autoantibodies. CONCLUSION: These observations suggest that the clinical syndromes defined by particular MSA are similar in children and adults with IIM. By defining similar clinical syndromes in children who have MSA, this study provides a basis for future studies of MSA in the idiopathic inflammatory myopathies of childhood, which may be useful in predicting the clinical courses of a subset of these patients and improving their therapy.

Adolescent↗
PubMed1994

New perspectives on the idiopathic inflammatory myopathies of childhood.

The idiopathic inflammatory myopathies (IIMs) of childhood are a heterogenous group of rare diseases characterized by chronic skeletal muscle inflammation. Although juvenile dermatomyositis is the most common of these disorders, children may develop any of the other types of myositis that have been better studied in adults. These include not only the IIMs delineated by clinicopathologic features but also the serologic groups of myositis, recently defined by myositis-specific and myositis-associated autoantibodies. Differences in the frequencies of IIM groups between children and adults suggest differences in exposures to myositis-inducing environmental agents or differences in the frequencies of susceptibility genes between these two populations. Further investigation of the heterogeneity of the childhood IIMs and of the newly described clinicopathologic and autoantibody groups should improve our understanding and treatment of these disorders.

Autoantibodies↗
PubMed1993

Treatment of neonatal lupus: case report and review of the literature.

A critically ill infant with congenital complete heart block and neonatal lupus was treated with pulse steroids, exchange transfusion and intravenous gammaglobulin. Transient improvement in clinical status and laboratory results occurred, although the infant died. Based on this report and review of prior experience with immunosuppressive therapy, prenatal treatment of the mother with betamethasone or dexamethasone has been successful in resolving the cardiomyopathy/myocarditis associated with neonatal lupus. Postnatal treatment of the infant with steroids appears to be beneficial for persistent hepatic and hematologic manifestations. The evidence for exchange transfusion is less certain.

Betamethasone↗
PubMed1988

Phorbol diesters and dioctanoylglycerol stimulate accumulation of both diacylglycerols and alkylacylglycerols in human neutrophils.

Human neutrophils treated with phorbol 12-myristate 13-acetate (PMA) or dioctanoylglycerol exhibited a large (10-fold), sustained accumulation of the mass of diradylglycerol, beginning 1 min after stimulation and continuing for 30 to 60 min. Phorbol dibutyrate was less potent than PMA in stimulating diradylglycerol accumulation, whereas the 4-alpha analogs of PMA and phorbol dibutyrate were inactive. Submaximal concentrations of PMA (0.5 to 2.5 nM) plus the calcium ionophore, ionomycin (15 to 60 nM), led to synergistic accumulation of diradylglycerols. Chlorpromazine and sphingosine, inhibitors of protein kinase C, blocked PMA-stimulated accumulation of diradylglycerol with IC50 concentrations of 32 and 9 microM, respectively, paralleling their inhibition of PMA-stimulated O2- production. These compounds also inhibited the ionomycin-stimulated accumulation of diradylglycerols. A third protein kinase C inhibitor, H-7, was less effective, inhibiting PMA-stimulated accumulation of diradylglycerol by 25% at 100 microM. Differential sensitivity to alkaline hydrolysis suggests that diradylglycerols that accumulate in response to PMA or ionomycin stimulation are composed of a mixture of two distinct diglyceride species, diacylglycerols and alkylacylglycerols. Whereas diacylglycerol may activate cellular protein kinase C, the importance of the production of alkylacylglycerols is uncertain.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1987

Diacylglycerol accumulation and superoxide anion production in stimulated human neutrophils.

Exogenous diacylglycerols stimulate neutrophil superoxide anion production, suggesting that endogenous diacylglycerols may function as second messengers for this biological response. We have measured the diacylglycerol mass in human neutrophils stimulated by fMet-Leu-Phe, ionomycin, and concanavalin A and have correlated the kinetics and magnitude of the diacylglycerol response with those for superoxide anion production. For each stimulus, no increase in diacylglycerol mass was detected prior to the onset of superoxide anion generation. However, large sustained increases in diacylglycerol concentration (260-2000% of basal levels) occurred in parallel with the rise in superoxide anion. The cessation or continuation of diacylglycerol accumulation and superoxide anion production also correlated. The diacylglycerol response was proportional to the stimulus concentration and correlated with the concentration dependence for superoxide anion. Pretreatment of neutrophils with cytochalasin B enhanced both superoxide anion and diacylglycerol responses with all three stimuli. These data support the hypothesis that diacylglycerol functions as a modulator of superoxide anion generation causing a sustained or augmented respiratory burst.

Concanavalin A↗
PubMedDate not supplied

Chimeric cells of maternal origin in juvenile idiopathic inflammatory myopathies. Childhood Myositis Heterogeneity Collaborative Group.

We identified maternal microchimerism by fluorescence in-situ hybridisation in magnetically-separated CD4 or CD8 peripheral blood cells of eight of nine male patients with juvenile idiopathic inflammatory myopathy, compared with two of nine healthy male controls. We also found maternal microchimerism in inflammatory lesions (one skin sample and nine muscle biopsy samples) of all ten patients examined, compared with two of ten biopsy samples from patients with other muscle disorders. These results suggest that maternal cells may be involved in the pathogenesis of juvenile idiopathic inflammatory myopathy.

Adolescent↗
PubMedDate not supplied

Autoantibody production in Kawasaki syndrome.

Although a variety of autoantibodies are produced in patients with Kawasaki syndrome (KS), their specificities in many instances are controversial and their role in disease pathogenesis is undetermined. Autoantibody production was studied in 14 patients with Kawasaki syndrome (KS). Antibodies to myeloperoxidase (MPO), the dominant antigen responsible for perinuclear antineutrophil cytoplasmic antibody (pANCA) reactivity, were detected by ELISA in 73% of acute phase and 89% of convalescent phase KS specimens, in contrast to 4% of normal adult control subjects (p < 0.002 and p < 0.001, respectively). MPO and cytoplasmic antineutrophil antibody (cANCA) levels measured by ELISA were significantly elevated above levels for adult normal control subjects (p < 0.005 and p < 0.01, respectively), but not above recently ill childhood controls. Among patients who developed a positive ANCA, antibody titers tended to rise in serial specimens despite clinical improvement. Antibodies to myocardial muscle, cardiac perimysial connective tissue, nuclear antigens (ANA), and smooth muscle were also detected in some KS patients, but titers did not differ significantly from control patients. Autoantibody results were not predictive of patients with echocardiographic abnormalities.

Antibodies, Antineutrophil Cytoplasmic↗