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Biomedical subjects

B D Williams

Publications and source records attributed to B D Williams.

At least 19 recordsLinked to original sources
PubMed2004

Algal degradation of a known endocrine disrupting insecticide, alpha-endosulfan, and its metabolite, endosulfan sulfate, in liquid medium and soil.

The role of algae in the persistence, transformation, and bioremediation of two endocrine disrupting chemicals, alpha-endosulfan (a cyclodiene insecticide) and its oxidation product endosulfan sulfate, in soil (incubated under light or in darkness) and a liquid medium was examined. Incubation of soil under light dramatically decreased the persistence of alpha-endosulfan and enhanced its transformation to endosulfan sulfate, over that of dark-incubated soil samples, under both nonflooded and flooded conditions. This enhanced degradation of soil-applied alpha-endosulfan was associated with profuse growth of indigenous phototrophic organisms such as algae in soil incubated under light. Inoculation of soil with green algae, Chlorococcum sp. or Scenedesmus sp., further enhanced the degradation of alpha-endosulfan. The role of algae in alpha-endosulfan degradation was convincingly demonstrated when these algae degraded alpha-endosulfan to endosulfan sulfate, the major metabolite, and endosulfan ether, a minor metabolite, in a defined liquid medium. When a high density of the algal inoculum was used, both metabolites appeared to undergo further degradation as evident from their accumulation only in small amounts and the appearance of an endosulfan-derived aldehyde. Interestingly, beta-endosulfan was detected during degradation of alpha-endosulfan by high density algal cultures. These algae were also capable of degrading endosulfan sulfate but to a lesser extent than alpha-endosulfan. Evidence suggested that both alpha-endosulfan and endosulfan sulfate were immediately sorbed by the algae from the medium, which then effected their degradation. Biosorption, coupled with their biotransformation ability, especially at a high inoculum density, makes algae effective candidates for remediation of alpha-endosulfan-polluted environments.

Chlorophyta↗
PubMed2003

Single value of serum transferrin receptor is not diagnostic for the absence of iron stores in anaemic patients with rheumatoid arthritis.

Serum transferrin receptor (sTfR) concentrations were measured in anaemic patients with rheumatoid arthritis (RA). Serum transferrin receptor concentrations were positively correlated with the percentage of hypochromic cells and negatively correlated with MCH. There was a weak correlation with serum ferritin (sFn) concentration but not with reticulocyte count. Thus, high concentrations of sTfR indicate iron-deficient erythropoiesis rather than levels of storage iron in the tissues. Patients were divided into three groups on the basis of sFn concentration: those with probable tissue iron deficiency, those with adequate iron stores and those with intermediate values of sFn which did not allow classification. The median sTfR concentration was significantly higher in the iron-deficient group than in the other two groups but because of overlap between the three groups, a single sTfR value was of limited value in determining the level of storage iron in an individual with RA.

Adult↗
PubMed2001

Partial tears of the distal biceps tendon: MR appearance and associated clinical findings.

PURPOSE: To describe the magnetic resonance (MR) appearance and associated clinical findings of partial distal biceps tendon tears. DESIGN: Twenty elbow MR images at 1.5 T, performed over a 7 year period, were reviewed for an appearance of partial tears in the distal biceps. These images were assessed by two musculoskeletal radiologists for the extent of: (a) abnormal signal intensity within the tendon, and the presence of (b) bicipitoradial bursitis, and (c) bony microavulsive injury of the radial tuberosity. Medical records for nine of the 20 cases were reviewed for the clinical findings of ecchymosis, trauma, sensation of a "pop", loss of function, and acuity of onset. RESULTS: Twenty partial distal biceps tendon tears were seen. All displayed an abnormally increased signal in the distal biceps tendon. Three of 20 (15%) showed a 25% to 50% tear, ten of 20 (50%) showed a 50% tear, and seven of 20 (35%) showed a 75% to 90% tear. Bicipitoradial bursitis was seen in 11 of 20 (55%) cases. Bony microavulsive injury of the radial tuberosity was observed in 10 of 20 (50%). Of the nine cases reviewed for associated clinical findings, surprisingly, only three (33%) experienced an acute traumatic episode with an abrupt onset of pain. An insidious onset was reported in four of nine (44%). Sensation of a "pop" was recorded in only two of nine (22%) cases. Ecchymosis and loss of function were not seen in any of the cases. Finally, surgical conformation was obtained for three cases. CONCLUSION: Partial distal biceps tendon tears have a characteristic MR appearance, demonstrate little functional deficit, and may be attritional in their etiology due to the observation of a low number of patients reporting trauma or an acute onset.

Adult↗
PubMed2001

Minocycline-induced lupus: clinical features and response to rechallenge.

OBJECTIVE: To describe the spectrum of clinical features in patients with minocycline-induced lupus (MIL) and determine their response to rechallenge. METHODS: The clinical features and laboratory findings of 23 patients with MIL were recorded. Ten patients were rechallenged, and their C-reactive protein (CRP) levels were monitored. RESULTS: All subjects complained of polyarthralgia; three had metacarpophalangeal and proximal interphalangeal joint synovitis and one had bilateral knee effusions. Elevated hepatic transaminases were noted in eight subjects. Cutaneous vasculitis was a feature in two cases. None had renal or central nervous system disease, although five patients complained of impaired concentration and poor memory and a single patient had a peripheral sensory neuropathy. The following serological abnormalities were detected: antinuclear antibodies (19/23 patients); antibodies to double-stranded DNA (4/23); perinuclear antineutrophil cytoplasmic antibodies (10/15); IgG anti-cardiolipin antibodies (6/23); hypergammaglobulinaemia (12/19). Anti-histone antibodies were negative in 9/9 cases. Rechallenge resulted in rapid recurrence of symptoms and elevation of CRP levels. CONCLUSION: MIL is associated with a wide spectrum of clinical and serological features. The diagnosis can be confirmed by rechallenge, which results in rapid reappearance of symptoms and a rise in CRP.

Adolescent↗
PubMed2001

Amelioration of rat antigen-induced arthritis by liposomally conjugated methotrexate is accompanied by down-regulation of cytokine mRNA expression.

OBJECTIVES: We examined the temporal changes in the expression of interleukin 1beta (IL-1beta), tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) in the rat antigen-induced arthritis (AIA) model and investigated how their expression was modulated following disease amelioration by liposomally conjugated methotrexate (G-MLV). METHODS: On the day of arthritis induction (day 0), rats were treated with a single intra-articular injection of G-MLV, methotrexate (MTX), a dose of lipid equivalent to G-MLV (E-LIPO) or saline. On days 3 and 7 after disease induction, animals from each experimental group were killed. Joint tissue was examined histologically and for mRNA expression (IL-6, IL-1beta and TNF-alpha) using semiquantitative reverse transcription-polymerase chain reaction. RESULTS: There was no significant difference (ANOVA) in knee swelling between MTX-, E-MLV- or saline-treated animals from day 0 to day 7. By day 1, G-MLV significantly reduced knee swelling (1.94+/-0.12 mm; P<0.0001) compared with rats treated with MTX (3.17+/-0.18 mm). G-MLV treatment also significantly inhibited the histological progression of AIA. This reduction in disease severity was accompanied by a reduction in IL-1beta mRNA expression in synovial tissue extracts on day 3 and IL-6 mRNA expression on both day 3 and day 7. CONCLUSIONS: Liposomally conjugated MTX may exert its beneficial effects in experimental arthritis through IL-1beta and IL-6 inhibition.

Animals↗
PubMed2001

Suppression of chronic streptococcal cell wall-induced arthritis in Lewis rats by liposomal clodronate.

OBJECTIVES: To investigate the role of macrophages in the pathogenesis of chronic streptococcal cell wall (SCW)-induced arthritis using liposomal clodronate. METHODS: Female Lewis rats with SCW-induced arthritis received a single intravenous injection of 20 mg of clodronate encapsulated within small unilamellar vesicles (SUVc) 10 days post-arthritis induction. RESULTS: SUVc significantly suppressed the development of chronic SCW-induced arthritis for up to 26 days after treatment. At this time point, ED1(+) macrophages were significantly depleted in the liver and ankle joints, although splenic macrophage numbers were not significantly different from control groups. Macrophage elimination induced a significant reduction in local levels of interleukin (IL)-1beta, IL-6, tumour necrosis factor-alpha (TNFalpha) and matrix metalloproteinase-9 (MMP-9) from ankle joints. CONCLUSIONS: Macrophage elimination by SUVc inhibits local production of IL-1beta, IL-6, TNFalpha and MMP-9, and the pathogenesis of inflammatory arthritis.

Animals↗
PubMed2001

Improved functional ability in patients with rheumatoid arthritis--longterm treatment with leflunomide versus sulfasalazine. European Leflunomide Study Group.

OBJECTIVE: We previously reported that the new disease modifying antirheumatic drug leflunomide resulted in significant improvement in functional ability compared with placebo and sulfasalazine in a 6 month double blind, randomized, Phase III trial in rheumatoid arthritis (RA). The current study compared functional disability in cohorts of patients with RA from the initial study who volunteered to continue treatment with leflunomide or sulfasalazine. METHODS: The Health Assessment Questionnaire (HAQ) was used to assess functional ability in patients completing 6 months of therapy who chose to continue in double blinded 12 and 24 month extensions. Patients on active regimens continued taking leflunomide 20 mg/day or sulfasalazine 2 g/day; those taking placebo were switched at Month 6 to sulfasalazine. RESULTS: Leflunomide significantly improved patients' functional ability compared to placebo (p < or = 0.0001) and sulfasalazine (p < or = 0.01) at 6 months. These changes were seen as early as Month 1, and continued improvements were seen in 12 and 24 month cohorts. Mean HAQ scores were significantly improved with leflunomide compared with sulfasalazine at 24 months (-0.65 vs -0.36; p = 0.0149); corresponding changes in HAQ Disability Index (DI) were -0.73 vs -0.56 and were not statistically different. Leflunomide is safe and well tolerated and no unexpected adverse events were noted during the 2 year period; diarrhea, nausea, and alopecia were less frequent with continued treatment. CONCLUSION: These longterm data confirm leflunomide improves functional ability as shown by reductions in HAQ scores. The benefit of leflunomide is reflected in other efficacy criteria, such as global assessments and the American College of Rheumatology response rates, all of which showed significantly more improvement with leflunomide than sulfasalazine at 24 months.

Adolescent↗
PubMed2001

Serum soluble interleukin 2 receptor levels and radiological progression in early rheumatoid arthritis.

OBJECTIVE: To investigate the association between serum soluble interleukin 2 receptor (sIL-2R) levels and radiological changes in patients with early rheumatoid arthritis (RA). METHODS: sIL-2R levels from 155 patients with active RA were measured by immunoassay over a 2 year period and the associations with radiological change and other measures of disease activity were analyzed. RESULTS: The area under the curve for sIL-2R is weakly associated with the change in the modified Larsen score over a 2 year period; this is weaker than the association of radiological change with serum C-reactive protein. CONCLUSION: We found no significant association of sIL-2R levels with erosive change in early RA.

Arthritis, Rheumatoid↗
PubMed2000

The UNC-112 gene in Caenorhabditis elegans encodes a novel component of cell-matrix adhesion structures required for integrin localization in the muscle cell membrane.

Embryos homozygous for mutations in the unc-52, pat-2, pat-3, and unc-112 genes of C. elegans exhibit a similar Pat phenotype. Myosin and actin are not organized into sarcomeres in the body wall muscle cells of these mutants, and dense body and M-line components fail to assemble. The unc-52 (perlecan), pat-2 (alpha-integrin), and pat-3 (beta-integrin) genes encode ECM or transmembrane proteins found at the cell-matrix adhesion sites of both dense bodies and M-lines. This study describes the identification of the unc-112 gene product, a novel, membrane-associated, intracellular protein that colocalizes with integrin at cell-matrix adhesion complexes. The 720-amino acid UNC-112 protein is homologous to Mig-2, a human protein of unknown function. These two proteins share a region of homology with talin and members of the FERM superfamily of proteins. We have determined that a functional UNC-112::GFP fusion protein colocalizes with PAT-3/beta-integrin in both adult and embryonic body wall muscle. We also have determined that UNC-112 is required to organize PAT-3/beta-integrin after it is integrated into the basal cell membrane, but is not required to organize UNC-52/perlecan in the basement membrane, nor for DEB-1/vinculin to localize with PAT-3/beta-integrin. Furthermore, UNC-112 requires the presence of UNC-52/perlecan and PAT-3/beta-integrin, but not DEB-1/vinculin to become localized to the muscle cell membrane.

Animals↗
PubMed2000

Therapeutic efficacy of a novel membrane-targeted complement regulator in antigen-induced arthritis in the rat.

OBJECTIVE: Complement system activation is strongly implicated as a factor in the pathogenesis of chronic synovitis in human rheumatoid arthritis. The objective of this study was to explore the therapeutic potential and local retention of a novel membrane-targeting complement regulatory protein, derived from human complement receptor 1, in the experimental setting of rat antigen-induced arthritis. METHODS: Sensitized animals were treated at the time of arthritis induction with a single intraarticular (IA) dose of the membrane-targeting regulator APT070, a non-membrane-targeting control regulator (APT898), or vehicle control, and disease was assessed clinically and histologically. In addition, immunocytochemical analysis was performed on sections from normal rat knee joints at various time points after IA injection with APT070. RESULTS: Animals treated with APT070 showed a dose-dependent therapeutic effect, with significantly milder clinical and histologic disease compared with both other treatment groups (P < 0.008 at the higher dose) and minimal evidence of erosive disease at study end in the active treatment group. Immunoperoxidase and immunofluorescence studies demonstrated local retention of APT070 on cell surface membranes within the normal joint up to 48 hours after IA injection. CONCLUSION: These results show that IA complement inhibition represents an effective therapeutic strategy in experimental arthritis, by demonstrating that the exogenous delivery of a membrane-targeting complement regulator can result in prolonged synovial cell surface binding and significant clinical benefit in vivo. Complement inhibitory strategies of this type should be considered as novel therapies in human inflammatory arthritis.

Animals↗
PubMed2000

Soluble complement receptor one (sCR1) inhibits the development and progression of rat collagen-induced arthritis.

We set out to determine whether inhibition of complement using sCR1 could influence the development and progression of collagen arthritis in the Lewis rat. Collagen arthritis was successfully established in the Lewis rat, using a novel immunization schedule. In separate experiments, cobra venom factor (CVF) and sCR1 were used to achieve systemic complement inhibition. Their respective effects on disease onset and on the progression of established disease compared with saline-treated control animals was explored. Arthritis was assessed by measurement of clinical score, paw diameter and paw volume. Complement inhibition using either CVF or sCR1, prior to the onset of clinical signs of inflammation, delayed the development of disease. CVF was ineffective in the treatment of established disease, whereas sCR1 delayed the progression of disease in affected joints and prevented the recruitment of further joints while the animals were complement-depleted. In the control saline-treated groups the disease continued to progress relentlessly. We conclude that complement activation is important in the initiation and maintenance of inflammation in collagen arthritis. The potent disease-modulating effect of sCR1 provides persuasive evidence that specific complement inhibiting agents may be an effective approach to the treatment of inflammatory joint diseases

Animals↗
PubMed1999

Genomic organization, expression, and analysis of the troponin C gene pat-10 of Caenorhabditis elegans.

We have cloned and characterized the troponin C gene, pat-10 of the nematode Caenorhabditis elegans. At the amino acid level nematode troponin C is most similar to troponin C of Drosophila (45% identity) and cardiac troponin C of vertebrates. Expression studies demonstrate that this troponin is expressed in body wall muscle throughout the life of the animal. Later, vulval muscles and anal muscles also express this troponin C isoform. The structural gene for this troponin is pat-10 and mutations in this gene lead to animals that arrest as twofold paralyzed embryos late in development. We have sequenced two of the mutations in pat-10 and both had identical two mutations in the gene; one changes D64 to N and the other changes W153 to a termination site. The missense alteration affects a calcium-binding site and eliminates calcium binding, whereas the second mutation eliminates binding to troponin I. These combined biochemical and in vivo studies of mutant animals demonstrate that this troponin is essential for proper muscle function during development.

Amino Acid Sequence↗
PubMed1999

Interleukin-1beta (IL-1beta) inhibition: a possible mechanism for the anti-inflammatory potency of liposomally conjugated methotrexate formulations in arthritis.

1. Liposomes with conventional and long-circulation times were employed as carriers for the methotrexate derivative MTX-gamma-DMPE (MTX-EPC and MTX-PEG respectively), their mechanism of action was investigated in vitro and in vivo and their therapeutic efficacy assessed using the rat collagen-induced arthritis (CIA) model. 2. At non-toxic dose, both MTX-EPC and MTX-PEG inhibited the lipopolysaccharide (LPS) induced release of IL-1beta from activated rat peritoneal macrophages (rPMPhi) in a dose and time dependent manner. Free methotrexate (MTX) was not active in this respect. After a single intravenous injection (i.v.), and at equivalent doses, both free MTX (500 microg) and MTX-EPC inhibited the LPS induced rise in plasma IL-1beta levels observed in MTX-PEG and saline treated rats. 3. When used to treat established CIA, MTX-EPC resulted in significantly lower clinical score (CS) (1.0+/-0.42 (P<0.001)) and hind paw diameter (HPD) (6.5+/-0.34 mm (P<0.001)) measurements than controls (3.0+/-0.26; 7.33+/-0.41 mm), after only two i.v. doses, and remained significantly lower for the entire experimental period. By day 24 both CS (2+/-0.61 (P<0.001)) and HPD (6.97+/-0.25 mm (P<0.002)) measurements had also become significantly lower in MTX-PEG treated rats than in saline treated controls (3.62+/-0.17, 7. 92+/-0.38 mm) and remained lower until day 30. Joint inflammation in MTX treated rats was completely ameliorated by day 20 but the health and well being of the animals was compromised and the experiment terminated at this time-point. 4. Our results clearly demonstrate that both MTX-EPC and MTX-PEG liposomes have potential for development into therapeutic modalities for the treatment of inflammatory joint disease in man.

Animals↗
PubMed1999

Pro-inflammatory effects of the aminobisphosphonate ibandronate in vitro and in vivo.

OBJECTIVES: To investigate the effects of the aminobisphosphonate, ibandronate, on the course of joint inflammation in rat antigen-induced arthritis (AIA) and the release of pro-inflammatory cytokines in partially purified human peripheral blood mononuclear cells (PBMC). METHODS: Rats with AIA received a single intra-articular injection of ibandronate (1 mg) 7 days post-arthritis induction and knee swelling was measured for 7 days thereafter. The effects of ibandronate (300 microg/ml) on PBMC cytokine production and activation marker expression were determined using polymerase chain reaction (PCR)/ELISA and FACS analysis, respectively. RESULTS: Joint swelling, associated with AIA, was sustained in ibandronate-treated rats compared with saline-treated control rats. Ibandronate stimulated the production of interferon gamma (IFN-gamma) in adherent PBMC, and increased the surface expression of FcgammaRI and HLA DP, DQ, DR on the adherent monocyte population. Activation by lipopolysaccharide (LPS) of PBMC previously incubated with ibandronate led to enhanced levels of tumour necrosis factor alpha (TNF-alpha) secretion, and this could be partially inhibited by neutralizing antibodies to IFN-gamma. CONCLUSIONS: The enhanced production of TNF-alpha by ibandronate-treated PBMC in vitro involves stimulation of adherent monocytes by IFN-gamma prior to LPS-induced activation. Similar cellular interactions may be involved in the pro-inflammatory effects of ibandronate in vivo.

Animals↗