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Biomedical subjects

L C Miller

Publications and source records attributed to L C Miller.

15 recordsLinked to original sources
PubMed1992

Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist.

Interleukin 1 receptor antagonist (IL-1ra), a naturally occurring polypeptide with amino acid sequence homology to interleukin 1 alpha (IL-1 alpha) and interleukin 1 beta (IL-1 beta), prevents Escherichia coli-induced shock and death. Both IL-1 and IL-1ra are produced by monocytes stimulated with lipopolysaccharide (LPS). Because interleukin 4 (IL-4) suppresses IL-1 production, we investigated whether IL-4 modulated IL-1ra synthesis in LPS-stimulated human peripheral blood mononuclear cells. IL-1 beta and IL-1ra were measured by specific RIAs. IL-4 alone (0.01-100 ng/ml) did not stimulate IL-1 beta synthesis but rather induced IL-1ra (4.82 +/- 0.94 ng/ml). LPS induced synthesis of both IL-1 beta (6.67 +/- 1.06 ng/ml) and IL-1ra (10.77 +/- 2.79 ng/ml). IL-4 suppressed LPS-induced IL-1 beta mRNA accumulation and synthesis. However, IL-4 acted synergistically with LPS in inducing IL-1ra. IL-4 enhanced LPS-induced IL-1ra mRNA accumulation 4-fold and IL-1ra protein synthesis nearly 2-fold. Moreover, IL-1ra mRNA levels were maximal after 6 hr of exposure to LPS but peaked within the first 3 hr in the presence of IL-4. IL-4 added as late as 12 hr after LPS stimulation still enhanced IL-1ra synthesis. In human peripheral blood mononuclear cells stimulated with IL-1 alpha, IL-4 markedly suppressed IL-1 beta production but enhanced IL-1ra synthesis greater than 2-fold. Because IL-4 favors synthesis of the natural antagonist IL-1ra over synthesis of the agonist IL-1, IL-4 may exert potent antiinflammatory effects on host responses to Gram-negative infections.

Gene Expression↗
PubMed1992

Methotrexate treatment of recalcitrant childhood dermatomyositis.

OBJECTIVE: To review the clinical course of 16 children with recalcitrant dermatomyositis (DM), who were treated with oral methotrexate (MTX) in addition to prednisone. METHODS: Sixteen patients with recalcitrant DM who were treated with MTX in addition to prednisone were followed between 1984 and 1990. The patients' clinical responses to treatment, including alterations in muscle strength and muscle enzyme levels, changes in prednisone dosage, and development of toxicity or complications were reviewed retrospectively. RESULTS: All 12 patients who received MTX for at least 8 months regained normal muscle strength. In 11 of the 12, the prednisone dosage could eventually be tapered to < or = 5 mg/day. Complications during MTX treatment required discontinuation of MTX in 5 patients, and were unrelated to the cumulative dose of the drug. Active disease recurred in 5 patients in whom MTX had been discontinued after apparent clinical remission had been achieved. CONCLUSION: MTX, in combination with prednisone, is a useful adjunct in the treatment of recalcitrant childhood DM. However, recurrence of disease after withdrawal of MTX suggests that the drug may have a suppressive, rather than a remittive, effect.

Adolescent↗
PubMed1992

Interleukin-1 (IL-1) receptor blockade reduces endotoxin and Borrelia burgdorferi-stimulated IL-8 synthesis in human mononuclear cells.

Interleukin-1 (IL-1) is a potent stimulator of IL-8 production by fibroblasts and monocytes. In the present study, we asked how much of endotoxin (LPS)-induced IL-8 production by human peripheral blood mononuclear cells was due to IL-1 induced by LPS. Cells were stimulated with either IL-1 beta, LPS, or Borrelia burgdorferi, and total IL-8 was determined by a specific radioimmunoassay. The addition of saturating concentrations of IL-1 receptor antagonist protein (IRAP) reduced the IL-1 beta-, LPS-, and B. burgdorferi-induced IL-8 synthesis by 85, 50, and 40%, respectively. Increasing the concentration of LPS did not affect the reduction in IL-8 synthesis observed in the presence of IRAP. Significant inhibition of the IL-1 beta-induced IL-8 synthesis was observed when IRAP was added 60 or 90 min after IL-1 beta; similarly, IL-8 synthesis after LPS was also reduced by delayed addition of IRAP. These data suggest that the ameliorative effects of IL-1 receptor blockade in models of inflammation and infection may be due, in part, to suppression of IL-1-induced IL-8.

Borrelia burgdorferi Group↗
PubMed1992

Live Borrelia burgdorferi preferentially activate interleukin-1 beta gene expression and protein synthesis over the interleukin-1 receptor antagonist.

Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty. Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1 beta and the IL-1 receptor antagonist (IL-1ra) in human peripheral blood mononuclear cells. Live B. burgdorferi induced fivefold more IL-1 beta than IL-1 alpha and sevenfold more IL-1 beta than IL-1ra; LPS or sonicated B. burgdorferi induced similar amounts of all three cytokines. This preferential induction of IL-1 beta was most dramatic in response to a low passage, virulent preparation of B. burgdorferi vs. three high passage avirulent strains. No difference in induction of IL-1ra was seen between these strains. The marked induction of IL-1 beta was partially diminished by heat-treatment and abrogated by sonication; IL-1ra was not affected. This suggested that a membrane component(s) accounted for the preferential induction of IL-1 beta. However, recombinant outer surface protein beta induced little IL-1 beta. By 4 h after stimulation, B. burgdorferi induced sixfold more IL-1 beta protein than LPS. In contrast to LPS-induced IL-1 beta mRNA which reached maximal accumulation after 3 h, B. burgdorferi-induced IL-1 beta mRNA showed biphasic elevations at 3 and 18 h. B. burgdorferi-induced IL-1ra mRNA peaked at 12 h, whereas LPS-induced IL-1ra mRNA peaked at 9 h. IL-1 beta synthesis increased in response to increasing numbers of spirochetes, whereas IL-1ra synthesis did not. The preferential induction by B. burgdorferi of IL-1 beta over IL-1ra is an example of excess agonist over antagonist synthesis induced by a microbial pathogen, and may contribute to the destructive lesion of Lyme arthritis.

Adult↗
PubMed1992

Musculoskeletal signs of metabolic and systemic diseases in childhood.

Many metabolic and systemic disorders affect the musculoskeletal system in growing children. This review surveys some of the recent literature in several diverse areas, including new radiologic methods to determine bone mineralization and their use in children with juvenile arthritis and other systemic diseases, bone disorders in childhood, and the association of endocrinopathies and musculoskeletal symptoms.

Child↗
PubMed1992

Serum interleukin-2 and tumor necrosis factor-alpha in primary biliary cirrhosis: decrease by colchicine and relationship to HLA-DR4.

Colchicine improves liver function tests and survival in primary biliary cirrhosis (PBC); however, its mechanism of action in PBC is unknown. Because elevated interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF) have been found in various inflammatory diseases, we measured serum levels of IL-2 and TNF in 28 PBC patients before and during treatment with either colchicine or placebo. Compared with normal controls, untreated PBC patients had increased serum IL-2 (39 +/- 13 U/ml vs. 0.8 +/- 0.5) and TNF (549 +/- 162 pg/ml vs. nondetectable). During colchicine treatment, both IL-2 and TNF levels decreased significantly (57 +/- 24 to 40 +/- 22, p less than 0.04; 586 +/- 295 to 445 +/- 295, p less than 0.02). No significant changes in IL-2 or TNF levels occurred in the placebo-treated patients. DR4-positive patients had elevated levels of IL-2 at entry, compared with DR4-negative patients (67 +/- 26 vs. 14 +/- 5, p less than 0.04). The effect of colchicine in PBC may be due, in part, to modulation of IL-2 and TNF levels. Alternatively, the changes in IL-2 and TNF may simply reflect the overall improvement in biochemical tests of liver function related to colchicine therapy. DR4 appears to relate to serum levels of these cytokines in PBC and, possibly, also to the response to colchicine.

Biological Assay↗
PubMed1991

Rheumatic fever, reactive arthritis, and musculoskeletal infections in children.

Infections may cause musculoskeletal symptoms either by inducing reactive disease or by directly infecting bone, joints, or muscle. Differentiation of reactive disease from direct infections of the musculoskeletal system is an important clinical problem. Both reactive disease and direct infections result from interactions of the host, the environment, and the infecting agent. This review provides an update of the recent literature on rheumatic fever, the classic example in rheumatology of reactive disease, and direct musculoskeletal infections.

Arthritis, Infectious↗
PubMed1976

Organization and development of brain stem auditory nuclei of the chicken: ontogeny of n. magnocellularis and n. laminaris.

Nucleus magnocellularis (NM) and nucleus laminaris (NL) are, respectively, second- and third-order auditory nuclei in the chicken brain stem. In this report the morphogenesis of these nuclei is examined. The times of origin of the cells of these nuclei were studied with 3H-thymidine autoradiography. The number of cells in each nucleus and their rostro-caudal distribution within each nucleus was determined in Nissl-stained sections at 9, 11, 13, 15, 17, 19, and 21 days of incubation. For the above ages the volumes of NM and NL were also calculated planimetrically and the rostro-caudal distribution of volume within each nucleus was studied.

Animals↗
PubMed1976

Method factors associated with assessment of child behavior: fact or artifact?

A sample of 64 phobic children between the ages of 6 and 16, with their general population matched controls, were rated by parents on the Louisville Behavior Check List and Louisville Fear survey and by School Behavior check list. The analysis of ratings by factor analysis revealed three instrument factors while a multiple discriminant analysis elicited a multidimensional phobic trait that crossed observers, situations, and instruments. The results are discussed in terms of the implications for multivariant analysis of behavior change as well as for classification of psychopathological disorders of childhood. The thesis is advanced that instrument factors elicited by factor analysis in psychotherapy change studies are statistical artifacts and that a multiple discriminant analysis is a more appropriate technique for the study of change as well as for classification.

Adolescent↗
PubMedDate not supplied

The health of children adopted from Romania.

OBJECTIVE: To determine the medical condition of Romanian adoptees and the effects of the Romanian orphanage system on their health. DESIGN: Case series. SETTING: The international adoption clinics at the University of Minnesota, Minneapolis, and the New England Medical Center, Tufts University, Boston, Mass. PARTICIPANTS: Sixty-five Romanian adoptees who were brought to the United States during a 12-month period beginning in October 1990. MAIN OUTCOME MEASURES: Incidence of hepatitis B, intestinal parasites, tuberculosis, syphilis, human immunodeficiency virus type 1, growth failure, and developmental delay. RESULTS: Although the adopted children were presumably chosen from the most vital and attractive adoptees, only 15% were judged to be physically healthy and developmentally normal. Fifty-three percent had serological evidence of past or present hepatitis B infection, and 20% of screened children tested positive for hepatitis B surface antigen. In children aged 7 months or older, the overall prevalence of chronic hepatitis B was 23%. Intestinal parasites were found in 33% of subjects, and 45% of infected children had two or more pathogens identified. All the children tested for human immunodeficiency virus type 1 were negative. Two patterns of growth failure were observed that resembled the two subtypes of psychosocial short stature that occur in association with prolonged psychological harassment or emotional deprivation. Infants' length, weight, head circumference, and weight-for-height were adversely affected by institutionalization. Older children's height was reduced. Only 10% of children older than 12 months were developmentally normal. CONCLUSION: Romanian adoptees are an extraordinarily high-risk pediatric group as a consequences of decades of government-sanctioned child neglect and abuse.

Adoption↗
PubMedDate not supplied

Evaluation of a media-based mammography program.

Reports indicate that only 15%-20% of women 50 years of age and older have had a mammogram. To promote screening mammography, the San Diego County Unit of the American Cancer Society sponsored a community-wide program that featured (1) discounted mammograms through participating clinics, (2) program promotion through television news, and (3) availability of a phone bank for obtaining referrals for mammography. Pre- and postintervention random sample phone surveys indicated that women's intentions to obtain a mammogram increased significantly after the media campaign, particularly in those aware of the program. Women's intentions after the media campaign predicted mammography compliance in the following year. A total of 3,102 women received mammograms directly through the program, with a "suspicious finding" rate of 4%. Participant satisfaction with the program was high.

Adult↗