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Biomedical subjects

D Butler

Publications and source records attributed to D Butler.

At least 199 records · Page 11Linked to original sources
PubMed1997

Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production.

Interferon-gamma-inducing factor (IGIF, interleukin-18) is a recently described cytokine that shares structural features with the interleukin-1 (IL-1) family of proteins and functional properties with IL-12. Like IL-12, IGIF is a potent inducer of interferon (IFN)-gamma from T cells and natural killer cells. IGIF is synthesized as a biologically inactive precursor molecule (proIGIF). The cellular production of IL-1beta, a cytokine implicated in a variety of inflammatory diseases, requires cleavage of its precursor (proIL-1beta) at an Asp-X site by interleukin-1beta-converting enzyme (ICE, recently termed caspase-1). The Asp-X sequence at the putative processing site in proIGIF suggests that a protease such as caspase-1 might be involved in the maturation of IGIF. Here we demonstrate that caspase-1 processes proIGIF and proIL-1beta with equivalent efficiencies in vitro. A selective caspase-1 inhibitor blocks both lipopolysaccharide-induced IL-1beta and IFN-gamma production from human mononuclear cells. Furthermore, caspase-1-deficient mice are defective in lipopolysaccharide-induced IFN-gamma production. Our results thus implicate caspase-1 in the physiological production of IGIF and demonstrate that it plays a critical role in the regulation of multiple proinflammatory cytokines. Specific caspase-1 inhibitors would provide a new class of anti-inflammatory drugs with multipotent action.

Animals↗
PubMed1997

The shear behaviour of the rabbit medial collateral ligament.

This study was conducted to determine whether load is transmitted via shear through the matrix between ligament fibres rather than solely as tension in the fibres. Thirty-six rabbit medial collateral ligaments were subjected to uniaxial tension tests. Twenty-four of these ligament complexes were incised laterally to create longitudinal shear planes, while the remaining 12 complexes served as controls. Data were used in conjunction with finite element models to determine how shear transfer, if any, occurred in the ligament. Non-linear, anisotropic, plane stress finite element models were able to simulate the non-linear structural behaviour shown by uncut control ligaments under normal tensile testing. The finite element models were also able to reproduce the ligament load deformation behaviour observed in the shear tests. Results indicated that some load was transferred between the collagen fibres and other constituents in the ground substance of these ligaments and possibly also through fibres missed during the cutting procedure. The exact manner in which the load was transmitted remains unclear and requires further investigation and quantification.

Animals↗
PubMed1997

Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count.

To evaluate diagnostic criteria, disease characteristics, and the clinical course of pediatric myelodysplastic syndrome (MDS), we reviewed 327 consecutive cases diagnosed with de novo acute myeloid leukemia (AML) or MDS at St Jude Children's Research Hospital between February 1980 and January 1993. Among 49 cases with <30% marrow blasts (consistent with FAB criteria and common diagnostic practice for MDS), eight had karyotypes associated with de novo AML (four with t(8;21)(q22;q22) and one each with inv(16)(p13q22), t(11;17)(q23;q21), t(9;11)(p22;q13), and i(1)(ql0)). We termed these cases AML with a low blast count (AML-LBC) and compared their clinical and morphologic features with those of the remaining 41 cases. AML-LBC cases had little or no hematopoietic dysplasia. MDS cases consisted of refractory anemia (RA, n=6), RA with ring sideroblasts (n=2), RA with excess blasts (RAEB, n=4), RAEB in transformation (n=14), and chronic myelomonocytic leukemia (n=15). Most had moderate/severe or multilineage hematopoietic dysplasia, with significantly higher dysplasia scores than AML-LBC cases (P=0.007). Only 30% of patients with MDS achieved complete remission (CR) after two cycles of AML-directed therapy, compared with 88% of patients with AML-LBC (P=0.0001); MDS patients tended to experience prolonged severe cytopenias with chemotherapy. The 4-year survival for MDS patients was 23% +/- 7% (s.e.), vs 50% +/- 18% (s.e.) for AML-LBC (P=0.048). AML-LBC patients frequently had chloromas; none were seen in MDS patients. We conclude that the 30% blast threshold is ineffective for separation of AML and MDS in pediatric patients, and that genetic data should be included in this decision process. AML-LBC, defined by <30% blasts in bone marrow and cyto- (or molecular) genetic abnormalities associated with de novo AML, and characterized by absent or mild marrow dysplasia, is biologically and clinically distinct from MDS and should be treated as de novo AML. Outcome in pediatric MDS remains poor, and new treatment strategies are needed for these patients.

Acute Disease↗
PubMed1997

Wilms' tumor in an adult: a case report and review of the literature.

Wilms' tumor in an adult is extremely rare, with less than 250 cases reported in the world literature. Treatment guidelines for pediatric Wilms' tumor are well established; those for adults are not. This article presents the case of a 19-year-old male diagnosed with Wilms' tumor after complaints of hematuria. He was categorized as Stage IV after nephrectomy and received post-operative radiotherapy and chemotherapy consisting of Vincristine, Adriamycin, and Actinomycin-D. Two years later he was found to have metastases to brain and lungs. He was treated with radiotherapy and bone marrow transplantation, and died of septic shock. The literature regarding Wilms' tumor in adults is reviewed, and current therapy is discussed.

Adult↗