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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 325 records · Page 18Linked to original sources
PubMed1998

European Multicentre Association Study of Schizophrenia: a study of the DRD2 Ser311Cys and DRD3 Ser9Gly polymorphisms.

As part of the European Multicentre Association Study of Schizophrenia (EMASS), we studied polymorphisms in the dopamine DRD2 and DRD3 receptor genes. The EMASS collaboration was established to create a large, statistically powerful sample of schizophrenic patients and controls from different European centres. Previous studies have suggested associations between schizophrenia and the Ser311Cys polymorphism in exon 7 of the dopamine DRD2 receptor gene [Arinami et al., (1994): Lancet 343:703-704] and a polymorphism Ser9gly in exon 1 of the dopamine DRD3 receptor gene [Crocq et al. (1992): J Med Genet 29:858-860]. We tested for these associations in samples of 373 and 413, and 311 and 306 patients and controls, respectively. We found no evidence for allelic association between schizophrenia and the Cys311 variant of the DRD2 receptor gene and no homozygotes for this variant were observed by any group. However, an excess of homozygotes for both alleles of the DRD3 polymorphism was observed in schizophrenic patients (chi2 = 8.54, P = 0.003, odds ratio = 1.64, 95% CI = 1.18-2.29). We also observed a significant excess of the 1-1 (Ser9Ser) genotype (chi2 = 8.13, P = 0.004, odds ratio = 1.7, 95% CI = 1.18-2.4). No evidence of heterogeneity between samples was detected and there was no evidence of an allelic association. These findings suggest that the rare Cys311 variant in exon 7 of the DRD2 receptor gene does not play a role in the pathogenesis of schizophrenia in European populations. Currently, our results do support the previous findings of an association between increased homozygosity of the Ser/Gly variant of the Dopamine D3 receptor gene and schizophrenia.

Alleles↗
PubMed1998

In search of a dose-response relationship with radiotherapy in the management of recurrent rectal carcinoma in the pelvis: a systematic review.

PURPOSE: A systematic review of the literature was undertaken to address the question: "What is the most effective dose fractionation schedule for the relief of symptoms in patients with pelvic recurrence from rectal or colorectal carcinoma?" METHODS AND MATERIALS: Cancerlit/Medline-computerized databases were searched between the years 1966-1996. Studies that explored the response to radiotherapy in patients with pelvic recurrence from rectal/rectosigmoid carcinoma were included. Factors that may contribute to differences in results were postulated in advance and the variations encountered between articles were presented. Articles with data applicable to recurrent disease only were included in the primary analysis. The effect of including articles that reported outcomes of recurrences with unresectable primaries and residual disease was presented as a sensitivity analysis. RESULTS: Only retrospective series (level V evidence) were available. The many sources of potential bias inherent in retrospective analyses make the data suitable for hypothesis generation only. Comparison of response was made between "lower" vs. "higher" doses, using 45-50 Gy as the dividing dose, base on the primary analysis. There were no significant differences observable in terms of initial response and the proportion maintaining a response at 6 months, within the range of doses employed. When data from articles that reported outcomes of recurrent disease with primary untreated cancers and postoperative residual disease were included, there was a suggestion for a more favorable response with higher doses. This requires cautious interpretation within the methodological limitations of the data. CONCLUSION: The optimal dose fractionation schedule for the palliation of pelvic recurrence from rectal carcinoma remains undefined. Well-designed randomized studies, with study arms that are sufficiently diverse biologically to allow the detection of a dose-response relationship if one existed, equipped with suitable symptom control end points, are necessary to provide a clinically relevant answer.

Dose-Response Relationship, Radiation↗
PubMed1998

Activation of the Jak2-Stat5 signaling pathway in Nb2 lymphoma cells by an anti-apoptotic agent, aurintricarboxylic acid.

Biological effects of many hormones and cytokines are mediated through receptor-associated Jak tyrosine kinases and cytoplasmic Stat transcription factors, including critical physiological processes such as immunity, reproduction, and cell growth and differentiation. Pharmaceuticals that control Jak-Stat pathways are therefore of considerable interest. Here we demonstrate that a single Jak-Stat pathway can be activated by aurintricarboxylic acid (ATA), a negatively charged triphenylmethane derivative (475 Da) with anti-apoptotic properties. In prolactin (PRL)-dependent Nb2 lymphocytes, ATA sustained cell growth in the absence of hormone and mimicked rapid PRL-induced tyrosine phosphorylation of Jak2 and activation of Stat5a and Stat5b with tyrosine phosphorylation, heterodimerization, DNA binding, and induction of the Stat5-regulated pim-1 protooncogene. ATA also mimicked PRL activation of serine kinases ERK1 and ERK2. However, unlike PRL, ATA did not regulate Stat1 or Stat3. ATA also did not affect Jak3, which is activated in these cells by interleukin-2 family cytokines. Although the mechanism and specificity by which ATA activates Jak2, Stat5, and ERKs in Nb2 cells are still unclear, the present study demonstrates that certain hormone or cytokine effects on Jak-Stat pathways can be discretely imitated by a low molecular weight, non-peptide pharmaceutical. The results are also consistent with Stat5 involvement in lymphocyte growth and survival.

Apoptosis↗
PubMed1998

Analysis of Bence Jones proteinuria by high resolution two-dimensional electrophoresis.

Analysis of Bence Jones proteinuria by high resolution two-dimensional electrophoresis (2-DE) and immunoblotting reveals a complex pattern of light chain (LC) isoforms corresponding to the free monoclonal Bence Jones protein and its fragments. Replica blotting gives duplicate blots for LC typing (lambda, chi) and, under the conditions employed, leaves sufficient protein for Coomassie Blue staining of the urinary protein profile and pIIMr determination of the LC isoforms. Carrier ampholytes (CAs, in our "simplified" 2-DE system) and immobilised pH gradients (IPGs, in the Multiphor 2-DE system) give similar LC isoform patterns. Artifacts, including cone-like distortions and trailing "piggyback" spots, are visualised with both 2-DE systems. IPGs are advantageous as they allow reproducible detection of strongly basic LC isoforms by isoelectric focusing (under equilibrium conditions) without recourse to CA nonequilibrium pH gradient electrophoresis.

Bence Jones Protein↗
PubMed1998

Blockade of CD40-CD40 ligand interactions protects against radiation-induced pulmonary inflammation and fibrosis.

This study investigated whether CD40-CD40 ligand (L) interactions are important in mediating ionizing radiation-induced lung toxicity. Radiotherapy is a key component in the management of malignant diseases and is a conditioning regimen for bone marrow transplantation. Unfortunately, radiation therapy is particularly toxic to the lung, potentially inducing a fatal pneumonitis and fibrosis, thus limiting its effectiveness. There are no therapies that protect against the development of radiation-induced lung toxicity. Using a mouse model of radiation-induced lung toxicity, a monoclonal anti-CD40L antibody (MR1) that disrupts CD40-CD40L interactions was tested for the ability to reduce lung injury. C57BL/6 mice were pretreated with either nothing, MR1, or hamster IgG 24 h prior to a single dose of 15 Gray ionizing radiation to the thorax. During the following 26 weeks, mice continued to receive MR1 or hamster IgG twice per week. MR1 protected against death from radiation pneumonitis and fibrosis and dramatically reduced lung pathology as evidenced by a limited influx of inflammatory cells, minimal collagen deposition, and septal thickening. MR1 also prevented radiation-induced pulmonary mastocytosis and blunted expression of cyclooxygenase-2, a proinflammatory enzyme responsible for prostaglandin synthesis. Disruption of CD40-CD40L interactions may offer a new mode of intervention to protect against radiation-induced pulmonary toxicity.

Animals↗
PubMed1998

Thoracic splenosis.

Thoracic splenosis is a rare pathologic entity resulting from seeding of splenic tissue in the pleural cavity after thoracoabdominal trauma. A 45-year-old man with a history of splenectomy secondary to abdominal trauma presented with a left lung mass and an inconclusive tissue diagnosis after needle biopsy. Thoracic splenosis was not suspected preoperatively, considered on an intraoperative frozen section, and established on permanent pathologic biopsy specimens obtained during thoracotomy. A history of thoracoabdominal trauma, combined with radiologic and radionuclide imaging studies, may establish the diagnosis without thoracotomy.

Abdominal Injuries↗
PubMed1998

A tale of two (low prevalence) cities: social movement organisations and the local policy response to HIV/AIDS.

In the field of HIV/AIDS, social movement organisations (SMOs) have been identified as powerful potential catalysts for change through their impact on formal organisational structures and the policy process. In addition, they have the capacity to be important providers of services in their own right, through the community resources they are capable of mobilising. In the United Kingdom, however, their role in policy formation is disputed. Previous studies have concluded that they have been most influential at national policy and ward level. At the level of local policy making, their influence has been found to be patchy and confined largely to securing recognition of HIV as an issue. Most previous research has, however, been conducted in high prevalence, metropolitan settings with functional SMOs. This paper presents the results of a comparative case study of two neighbouring provincial low prevalence district health authorities (HAs) in England. We describe the changing national policy context from 1986 to 1995 and use a strategic change model to analyse the local development of care and treatment services for people with HIV/AIDS, in particular the relationship between SMOs and HAs. Despite being demographically, socioeconomically and epidemiologically similar, and sharing an identical national policy framework, the two districts demonstrate completely divergent organisational responses to the HIV/AIDS epidemic. We conclude that the level of prior social movement mobilisation and the degree of receptivity for change within the HA are the key variables for explaining variations in the scale of strategic change observed in the two districts.

Adult↗
PubMed1998

Application of an immunoassay to determine risk factors associated with porcine cysticercosis in rural areas of Yucatan, Mexico.

A Western blot assay for identification of 26 kDa and/or 8 kDa antigens in a crude saline extract (CSE) of Taenia solium metacestodes, previously developed for human cysticercosis, was evaluated for use with pigs. The test population used for assay standardisation consisted of 45 cysticercotic pigs (5 pigs positive by necropsy and 40 selected by tongue palpation and LL-Gp immunoblot but not confirmed by necropsy), 48 pigs with heterologous infections and 40 negative controls from endemic and non-endemic areas. The test detected 93% of the cysticercotic group and was 100% specific. In a field study this antigen preparation was compared by immunoblot with antibody recognition for Gp13-50 antigens in a lentil-lectin semi-purified glycoprotein extract of T. solium (LL-Gp). The seroprevalence to CSE antigen was slightly lower (26/75) when compared to LL-Gp (29/75) and this represented a non-significant difference. The CSE Western blot assay was used to assess seroprevalence of T. solium cysticercosis in pig populations in the state of Yucatan, Mexico. A total of 1099 pigs sampled at random from 25 villages revealed a seroprevalence of 23% (253/1099). Seroprevalence in intensively reared, farmed pigs was 2% (7/228). In comparison with farmed pigs, the seroprevalence was 33% (172/513) in free-roaming backyard pigs (OR=13.86, CI=4.0747.22, p<10(-6)) and 25% (74/98) in semi-confined backyard pigs (OR=14.03, CI=5.60-35.16, p<10(-6)). There was no significant difference in seroprevalence by sex (p=0.23). Seroprevalence decreased with age (chi(2)-test for linear trend=7.803, p<0.006). Results of this study demonstrate that the CSE Western blot can be applied for reliable immunodiagnosis of T. solium cysticercosis in pigs. Furthermore, variation in pig husbandry in Yucatan indicated significantly higher exposure to cysticercosis in free-roaming backyard pigs compared to intensively reared animals from the same area.

Age Factors↗
PubMed1998

Trends in the quality of care for Medicare beneficiaries admitted to the hospital with unstable angina.

OBJECTIVES: We sought to 1) determine the proportion of appropriate elderly patients admitted to the hospital with unstable angina who are treated with aspirin and heparin; 2) identify patient factors associated with the Agency for Health Care Policy and Research (AHCPR) guideline-based use of aspirin and heparin; and 3) compare practice patterns and patient outcomes before and after publication of the AHCPR guidelines. BACKGROUND: Improving the care of patients with unstable angina may provide immediate opportunities to mitigate the adverse consequences of unstable angina. However, despite the importance of this diagnosis, there is a paucity of information on the patterns of treatment and outcomes across diverse sites and recent trends in practice that have occurred, especially since the publication of the AHCPR practice guidelines. METHOD: We performed a retrospective cohort study using data created from medical charts and administrative files. The sample included 300 consecutive patients admitted to one of three Connecticut hospitals in the period 1993 to 1994 and 150 consecutive patients admitted in 1995 with a principal discharge diagnosis of unstable angina or chest pain. RESULTS: Of the 384 patients > or =65 years old who had no contraindications to aspirin on hospital admission, 276 (72%) received it. Of the 369 patients > or =65 years old who had no contraindications to heparin on admission, 88 (24%) received it. Among the 321 patients > or =65 years old who had no contraindications to aspirin at hospital discharge, 208 (65%) were prescribed it. When 1995 was compared with 1993 to 1994, the use of aspirin (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.3 to 4.0) and heparin (OR 2.8, 95% CI 1.6 to 4.9) on hospital admission significantly increased, and the use of aspirin at discharge (OR 1.4, 95% CI 0.8 to 2.4) increased. Concomitantly, there was a significant reduction in 30-day readmission (OR 0.52, 95% CI 0.27 to 0.99). CONCLUSIONS: Our results indicate an improvement in the care and outcomes of elderly patients with unstable angina, but there remain opportunities for further improvement.

Aged↗
PubMed1998

Ratite diagnostic imaging.

Diagnostic imaging of ratite species is a challenge, even to the specialist. A portable radiography unit is frequently inadequate to penetrate the coelomic cavity of large birds, but should provide diagnostic quality radiographs of the extremities. Ultrasonography allows visualization of the coelomic structures, but will not penetrate gas or air. Use of both technologies often provides diagnostic information helpful to the clinician.

Animals↗
PubMed1998

Cognition and behavior after temporal lobectomy in pediatric patients with intractable epilepsy.

The increased use of surgical intervention for intractable epilepsy during childhood has resulted in a critical need for information concerning possible cognitive and behavioral changes in pediatric patients after surgery. In this pilot study, comprehensive neuropsychologic evaluations were completed on nine children who had a temporal lobectomy for intractable epilepsy before 16 years of age. Performances before and after surgery were compared using cognitive and behavioral measures. Repeated measures analysis of variance did not indicate differences in performance on the basis of laterality of surgery, although the number of left (n = 5) vs right (n = 4) temporal resections was small. Paired comparison t tests, which included all patients, did not suggest marked changes in cognitive functioning after surgery, although decreases in delayed verbal memory were evident. Positive effects on quality of life during the first year after surgical intervention were suggested by reduced internalizing symptoms and increased social interaction. Replication of this study is recommended with a larger number of patients and multicenter collaboration.

Adolescent↗
PubMed1998

Morphometric assessment of the innominate vein in the prediction of persistent left superior vena cava.

This study sought to develop a simple echocardiographic predictor of persistent left (L) superior vena cava (SVC) in subjects with bilateral SVC. Two groups of children were studied: one with known LSVC (n = 19) and the other, a control group, without LSVC (n = 15). Both groups were of similar age (3.5 +/- 3.0, mean +/- SD vs 3.8 +/- 3.1 years; p = 0.8) and weight (14.6 +/- 7.1 vs 15 +/- 8 kg; p = 0.9). The left innominate vein was either absent (n = 11) or hypoplastic (n = 8) in the LSVC group. The ratio of the innominate vein to the innominate artery was found to be independent of age or body surface area but was significantly smaller in the LSVC group than in the control group (0.33 +/- 0.1 vs 0.97 +/- 0.1; p < 0.001). A cutoff value of 0.47 or less discriminated the LSVC group from the control subjects. Interobserver and intraobserver variations, although important, did not influence the discriminating value of the ratio in the diagnosis of LSVC. Validation of the proposed ratio in 30 consecutive prospectively studied patients with LSVC proved to be 100% sensitive in predicting LSVC. No false-positive diagnosis of LSVC was made when this principle was applied. Absent or hypoplastic left innominate vein measuring 0.47 or less of the innominate artery is an easily recognizable and reliable echocardiographic predictor of LSVC.

Brachiocephalic Veins↗
PubMed1998

Neuropsychological patterns in pediatric epilepsy.

Results from comprehensive neuropsychological assessments of children diagnosed with epilepsy have rarely been reported. Previous research has generally focused on the measurement of overall intellectual ability and achievement skills. In the present study, neuropsychological evaluations including memory, attention, language, achievement, fine motor, executive function, visual motor integration, and behavior were completed on children (n = 79) diagnosed with epilepsy. Neurocognitive skills were within expectations for measured intelligence with the exception of verbal and visual attention skills, which were significantly below expectations based on measured ability. Behaviorally, children were rated by their parents as demonstrating clinically elevated attentional problems. Differences in cognitive and behavioral function were not found according to seizure type. Findings suggested a more diffuse effect of childhood epilepsy reflected in a pattern of decreased attention skills.

Adolescent↗
PubMed1998

The spectrum of neurocristic cutaneous hamartoma: clinicopathologic and immunohistochemical study of three cases.

Neurocristic cutaneous hamartomas result from aberrant development of the neuromesenchyme. Thus, the elements within these tumors reflect the spectrum of differentiation that results from migration of neural crest-derived cells. We present three cases, in addition to routine hematoxylin-eosin staining, a battery of immunohistochemical staining, including S-100 protein, HMB-45, EMA, CD34, and neurofilament-protein stains, was performed on each specimen. A dermal melanocytic component was the dominant feature of two of these lesions, while neurosusenticular and neuromesenchymal components dominated in one tumor. Both tumors that developed on the scalp showed effects on the overlying epidermis and/or on adnexal development. The melanocytic component was positive for S-100 protein and HMB-45. The surrounding stroma showed tactoid bodies and increased CD34 staining. Neurocristic cutaneous hamartomas represent dysplastic development of neural crest-derived cells. Although melanocytic cells have been previously reported to be the dominant cell population, neurosusentacular and neuromesenchymal cells also may be the principal component. In cephalic areas, the neuromesenchyme may not only be an important component of the tumor, but may also effect the development of the overlying epithelium and adnexal structures. Although none of these cases presents evidence of malignant transformation, identification of these tumors could be important if malignant transformation results in the development of tumors with a distinctive biologic behavior.

Adult↗