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Biomedical subjects

M D Smith

Publications and source records attributed to M D Smith.

At least 55 records · Page 3Linked to original sources
PubMed2002

Posttransplant lymphoproliferative disorders in lung transplant patients: the Cleveland Clinic experience.

PTLD is a well-recognized complication of organ transplantation. Large series of heart, renal, and liver transplants have been examined for the incidence and behavior of PTLD. However, reports of the incidence and characteristics of PTLDs in lung transplant (LTx) patients are few. We report our experience with PTLDs in a large series of LTx recipients at a single institution and compare them to other solid organ transplant recipient PTLDs seen at our institution. Twenty-eight patients were found to have PTLD, of whom 8 were lung transplant recipients. We evaluated nine PTLD specimens from these 8 patients for their histology, immunophenotype (CD20, CD3, EBV-LMP1), EBER status by in situ hybridization, and clinical features. The incidence of PTLD was 3.3% (8/244 patients). The time to development of PTLD, after transplant, was short (median time, 7 mo). All were of B-cell lineage. Overall, EBV was demonstrated in 77.7% (7 of 9 specimens) of PTLDs. All specimens tested for clonality were found to be monoclonal. Five patients died, with a median time to death of only 4.6 months. PTLDs in LTx patients are EBV-associated B-cell, predominantly monoclonal lymphoid lesions similar to other solid organ transplant PTLDs. Compared with other solid organ transplant recipients with PTLD at our institution, PTLDs in LTx patients have a propensity to involve the transplanted organ (P =.001, Fisher's exact test), occur earlier after transplant (P =.003, Wilcoxon test), and have a shorter survival (P =.002, log rank test). Reasons for this may include the relatively higher level of immunosuppression required in these patients and limited options in decreasing it. Although the incidence is low, careful early monitoring of lung transplantation patients is warranted because of the poor prognosis of patients developing this complication.

Adult↗
PubMed2002

Modelling mutagenicity using properties calculated by computational chemistry.

The recent advances in combinatorial chemistry and high throughput screening technologies have led to an explosion in the numbers of possible therapeutic candidates being produced at the early stages of drug discovery. This rapid increase in the number of chemicals to be classified results in a greater need for alternative methods for the prediction of toxicity. Most QSAR models for mutagenicity have been constructed for congeneric series. The prediction requirements of the pharmaceutical industry, however, cover quite diverse chemical structures. This paper reports a study of mutagenicity data for a diverse set of 90 compounds. Good discriminant models have been built for this data set using properties calculated by the techniques of computational chemistry. Jack-knifed (leave one out) predictions for these models are of the order of 85%.

Discriminant Analysis↗
PubMed2002

Analgesia for pelvic brachytherapy.

Pelvic brachytherapy presents the anaesthetist with numerous challenges. Patients vary from highly distressed young adults, to the elderly with coincidental disease severe enough to preclude surgery. The painful radioactive implants remain in place for a number of days. Treatment in isolated rooms reduces radiation exposure to staff, but makes close postoperative monitoring difficult, so the analgesic technique should involve minimum risk to the patient. Although there is very little published evidence of specific analgesic techniques in this area, knowledge of these problems allows the anaesthetist to select appropriate systemic analgesics and regional blocks to provide safe and effective pain relief.

Analgesia↗
PubMed2002

Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations.

OBJECTIVE: Cytokines play an important role in the pathology of rheumatoid arthritis (RA). Macrophage migration inhibitory factor (MIF) is a cytokine with a broad spectrum of actions, including induction of monocyte tumour necrosis factor alpha (TNF-alpha). Evidence of the expression and proinflammatory activity of MIF has recently been demonstrated in RA synovium and in animal models of RA. We wished to assess the relationship between MIF expression in synovium and clinical disease. METHODS: Computer-assisted analysis of the cytokine content of arthroscopically obtained biopsies of RA synovium, using paired samples from eight patients with active and inactive/treated disease, was compared with documented clinical parameters. RESULTS: Synovial MIF immunostaining correlated strongly with disease activity as measured by CRP concentration. Reductions in clinical disease parameters, including CRP, tender and swollen joint counts, were accompanied by significant reductions in synovial MIF. Synovial TNF-alpha, transforming growth factor beta (TGF-beta) and interleukin (IL) 10 also showed a significant reduction in association with reduced disease activity, while IL-1 beta and IL-1 receptor agonist did not. CONCLUSION: The correlation of synovial MIF with disease activity corroborates existing evidence of the role of this cytokine in RA. The demonstration that only MIF and TNF-alpha show significant variation in synovial cytokine content with clinical remission suggests that MIF is an important member of the cytokine hierarchy in RA.

Aged↗
PubMed2002

Receptor activator NF-kappaB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis.

OBJECTIVES: To compare receptor activator of NF-kappaB ligand (RANKL) production in the synovial tissue from patients with active rheumatoid arthritis (RA), inactive RA, spondyloarthropathies (SpA), osteoarthritis, and from normal subjects. In addition, to establish the cell lineages expressing RANKL in these tissues. METHODS: Immunohistological analysis of frozen synovial tissue biopsy specimens was performed using a monoclonal antibody (mAb) to detect RANKL. Sections were evaluated by computer assisted image analysis and semiquantitative analysis to compare RANKL expression between groups. Dual and sequential labelling with mAb RANKL and cell lineage specific monoclonal antibodies were used to determine the types of cells expressing RANKL. RESULTS: Higher levels of RANKL were expressed in tissues from patients with active RA and SpA than in tissues from patients with inactive RA, osteoarthritis, and from normal subjects. RANKL protein was associated with CD3 antigen-positive lymphocytes and some macrophages. RANKL was predominantly associated with activated, memory T cells (CD45Ro positive cells) in patients with active RA and spondyloarthropathy (SpA). CONCLUSIONS: The highest levels of RANKL were detected in patients with RA with active synovitis and in some patients with SpA. An increase in RANKL in the inflamed joint of patients with RA, produced by infiltrating activated T cells and macrophages, is likely to be an important cause of joint erosions in RA.

Adult↗
PubMed2002

In vitro performance characteristics of a high-flux hemodialyzer with a novel polyester-polymer-alloy (PEPA) membrane.

Despite improvements in hemodialyzers with respect to their clearance of middle and high molecular mass molecules, accumulation of specific solutes in the circulation of dialysis patients continues to be a medical problem. A new membrane material, polyester-polymer alloy (PEPA) which has been developed to have a filtration profile akin to that of the natural kidney, is now being used in hemodialyzers. This study evaluates the performance of a PEPA-based hemodialyzer alongside a selection of available competing high-flux dialyzers using official standardized methods. The new membrane material appears to be a viable alternative which offers performance at least as good as that of the competition. The promising results obtained with the PEPA membrane suggest that a detailed clinical performance study should be undertaken.

Alloys↗
PubMed2002

Antibody-based approach to high-volume genotyping for MIC-1 polymorphism.

Macrophage inhibitory cytokine-1 (MIC-1) is a divergent member of the TGF-beta superfamily. There are at least two known alleles of MIC-1 that are due to a G-->C point substitution at position 6 of the mature protein, which alters a histidine to an aspartic acid (MIC-1 H and MIC-1 D). We have determined the phenotype of MIC-1 circulating in serum by exploiting the differences in the affinity of the two monoclonal antibodies to the H and D alleles of MIC-1. A PCR-RFLP-based method for genotyping MIC-1 is also described. We validate these two assays using DNA sequencing of 19 subjects as the standard. We then used the validated assay to determine the frequency of the two MIC-1 alleles in a population of 261 adult blood donors. Inter-assay and sequencing concordance was 100%. The frequency of the three common MIC-1 genotypes was homozygous (HH), 54%; heterozygous (HD), 39%; and homozygous (DD), 7%. This novel antibody-based assay confidently determines the genotype of MIC-1. It offers the advantages of an ELISA-ease of automation, high-volume throughput of samples, and ease of use in a routine, clinical laboratory.

Adolescent↗
PubMed2001

Influence of a partner's HIV serostatus, use of highly active antiretroviral therapy, and viral load on perceptions of sexual risk behavior in a community sample of men who have sex with men.

OBJECTIVE: To assess the perceptions of gay and bisexual men concerning the risk of HIV transmission through various sexual practices with a new sex partner depending on that partner's disclosed HIV status, antiretroviral treatment status, and viral load. METHODS: Study participants read four different scenarios describing sexual situations with a new partner and rated each scenario for risk of HIV transmission. HIV status and antiretroviral treatment status disclosed by the new sex partner were varied across four scenarios: unknown HIV status; HIV-negative; HIV-positive and not taking highly active antiretroviral therapy (HAART); and HIV-positive and taking HAART with an undetectable viral load. RESULTS: Study participants were 472 men attending a gay pride festival who reported that they were HIV-negative. Eighty-nine percent of the men were white, and the mean age of the study participants was 35.8 years. Of the four scenarios, sex with an HIV-positive partner not taking HAART was rated as posing the greatest risk. Sex with an HIV-positive partner taking HAART who had an undetectable viral load was not consistently viewed as riskier than sex with an HIV-negative partner or a man with an unknown HIV status. CONCLUSIONS: The current study provides preliminary evidence for the effect of disclosure of HIV serostatus, use of HAART, and the presence of an undetectable viral load on the perceptions of sexual risk for HIV-negative men. The findings suggest that some gay and bisexual men judge risk based on the perceived HIV status of their sex partners and not on the general assumption that all sex partners entail equal risk, as many prevention campaigns have emphasized.

Adult↗
PubMed2001

A new packing variant of catena-poly[[aquachlorocopper(II)]-mu-pyrazine-2-carboxylato-O,N:N'].

Single crystals of the title coordination polymer, [CuCl(C5H3N2O2)(H2O)], have been prepared by hydrothermal synthesis. The compound is composed of infinite one-dimensional chains of pseudo-square-pyramidal Cu(II) ions connected via pyrazine-2-carboxylate ligands. A network of O-H...O hydrogen bonding between adjacent chains is responsible for a bilayer structure different from the previously reported polymorph.

Journal Article↗
PubMed2001

Supramolecular structures of cadmium(II) coordination polymers: a new class of ligands formed by linking tripodal tris(pyrazolyl)methane units.

The new ligands C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2) (pz = pyrazolyl ring), 1 (ortho), 2 (meta), and 3 (para), that can potentially bond two or more metal centers were obtained in a single step from the reaction of the appropriate dibromoxylene, 2 equiv of tris-2,2,2-(1-pyrazolyl)ethanol, and excess NaH. Although the arrangement of the tris(pyrazolyl)methane units in the solid-state structures of 1 and 3 are similar, the orientation of these groups with respect to the phenyl ring are different, with 1 showing a twisted structure and 3 a stepped structure. The reaction of [Cd(2)(THF)(5)][BF(4)](4) with the appropriate ligand yields each of the three coordination polymers of the formula [C(6)H(4)[CH(2)OCH(2)C(pz)(3)](2)Cd](BF(4))(2)](n), 4 (ortho), 5 (meta), and 6 (para). In the solid-state structures of all three each tris(pyrazolyl)methane unit is tridentate, with each ligand bonded to two different cadmium(II) atoms, forming a coordination polymer containing 6-coordinate, pseudooctahedral cadmium(II) centers. Polymers 4 and 5 form wavelike chains whereas 6 is arranged in a stepped structure similar to the free ligand. The different connecting patterns of each ligand lead to very different supramolecular structures, structures organized by the BF(4)(-) groups through weak C-H...F hydrogen bonds. Crystallographic information: 1 is monoclinic, P2(1)/n, a = 16.3157(13) A, b = 8.5880(6) A, c = 21.9227(17) A, alpha = gamma = 90 degrees, beta = 100.134(2) degrees, Z = 4; 3 is monoclinic, P2(1)/n, a = 9.1965(9) A, b = 12.9185(12) A, c = 12.7306(12) A, alpha = gamma = 90 degrees, beta = 104.099(2) degrees, Z = 2; 4 is triclinic, P1, a = 10.7877(19) A, b = 12.582(2) A, c = 15.409(3) A, alpha =103.860(4) degrees, beta = 94.123(4) degrees, gamma = 92.573(4) degrees, Z = 2; 6 is monoclinic, C2/c, a = 23.023(3) A, b = 12.2588(14) A, c = 18.119(2) A, alpha = gamma = 90 degrees, beta = 121.281(2) degrees, Z = 4.

Journal Article↗
PubMed2001

Ca(4)IrO(6), Ca(3)MgIrO(6) and Ca(3)ZnIrO(6).

Single crystals of tetracalcium iridium hexaoxide, Ca(4)IrO(6), tricalcium magnesium iridium hexaoxide, Ca(3)MgIrO(6), and tricalcium zinc iridium hexaoxide, Ca(3)ZnIrO(6), were prepared via high-temperature flux growth and structurally characterized by single-crystal X-ray diffraction. The three compounds are isostructural and adopt the K(4)CdCl(6) structure type, comprised of chains of alternating face-shared [CaO(6)], [MgO(6)] or [ZnO(6)] trigonal prisms and [IrO(6)] octahedra, surrounded by columns of Ca(2+) ions.

Journal Article↗
PubMed2001

The POU domain transcription factor Brn-3a protects cortical neurons from apoptosis.

We have demonstrated previously that exogenously expressed Brn-3a is capable of protecting neurons of the peripheral nervous system against apoptosis. In these previous studies Brn-3a showed a degree of neuronal sub-type specificity, in that while it could promote survival in NGF-dependent sensory neurons, no effect was observed in NGF-dependent neurons of the sympathetic nervous system. In this report, we show that Brn-3a delivered using a herpes simplex virus is capable of protecting cultures of rat cerebrocortical neurons of the central nervous system against two types of cell death stimuli, including glutamate neurotoxicity. Hence the protective effect of Brn-3a is not confined to neurons of the peripheral nervous system but can also occur in neurons of the CNS.

Animals↗