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Biomedical subjects

C Wilson

Publications and source records attributed to C Wilson.

At least 235 records · Page 13Linked to original sources
PubMed1997

Improving the detection rate of early gastric cancer requires more than open access gastroscopy: a five year study.

BACKGROUND/AIMS: To explore the reasons why patients with gastric cancer continue to present with advanced disease despite open access gastroscopy. PATIENTS: All patients diagnosed with gastric cancer between 1 August 1989 and 31 July 1994. METHODS: A retrospective study of the presentation of gastric cancer in South Tees; patients were diagnosed at open access gastroscopy or referred through conventional channels. Primary care records of 81 patients dying between 1991 and 1995 were analysed for previous symptoms, investigations, and antisecretory drug therapy. Findings were compared with 200 age and sex matched controls. RESULTS: The overall incidence of earlier stage gastric cancer remains low at 13%. Diagnostic delay occurs in both primary and secondary care due to a high incidence of previous dyspepsia and investigation. One in six patients had been previously investigated in the three years prior to diagnosis, the majority of whom were on antisecretory drugs. CONCLUSIONS: Early gastric cancer remains rare in South Tees health district. Advantages of open access gastroscopy appear to be compromised by delayed referral to hospital and failure of endoscopists to recognise the early disease; either they are unaware of its appearance or prior treatment with an H2 receptor antagonist masks the disease by allowing mucosal healing.

Aged↗
PubMed1997

Migratory abilities of different vascular cells from the tunica media of canine vessels.

In response to injury, vascular smooth muscle cells (VSMC) are thought to migrate toward the area of damage, where they participate in the reparative process. We have recently identified and isolated two distinct cell types (VSMC and type 2 cells) from the tunica media of canine carotid artery and saphenous vein. The purpose of these experiments was to determine whether both cell types were able to migrate in response to a variety of chemoattractants. A multiwell Boyden chamber and a wound migration assay were used to assess the migratory ability of these cells in vitro. The results indicated that VSMC did not exhibit directed migration in response to either 10% fetal bovine serum or platelet-derived growth factor (PDGF)-AB. In contrast, type 2 cells migrated to serum, PDGF-AB, and PDGF-BB but not to PDGF-AA, endothelin (ET)-1, or ET-3. No difference in migratory ability was detected between type 2 cells isolated from carotid arteries or saphenous veins. It is concluded that the migratory ability of cells within the tunica media of vessels from adult animals are not equal, suggesting that only selected cells may participate in vascular wall repair.

Animals↗
PubMed1997

Bovine spongiform encephalopathy: is it an autoimmune disease due to bacteria showing molecular mimicry with brain antigens?

Bovine spongiform encephalopathy (BSE) could be an autoimmune disease produced following exposure of cattle to feedstuffs containing bacteria showing molecular mimicry between bacterial components and bovine tissue. Analysis of molecular sequence databases (Genbank and SwissProt) shows that three bacteria (Acinetobacter calcoaceticus,Ruminococcus albus, and Agrobacter tumefaciens) share sequences with the encephalitogenic peptide of bovine myelin, while three molecules in Escherichia coli show molecular mimicry with host-encoded prion protein. Immune responses against these bacteria at both T and B cell levels may cause neurological tissue injury resembling BSE. The role of these bacteria in BSE, if any, merits further investigation.

Animal Feed↗
PubMed1997

High definition 3D ultrasound imaging.

We have demonstrated high definition and improved resolution using a novel scanning system integrated with a commercial ultrasound machine. The result is a volumetric 3D ultrasound data set that can be visualized using standard techniques. Unlike other 3D ultrasound images, image quality is improved from standard 2D data. Image definition and bandwidth is improved using patent pending techniques. The system can be used to image patients or wounded soldiers for general imaging of anatomy such as abdominal organs, extremities, and the neck. Although the risks associated with x-ray carcinogenesis are relatively low at diagnostic dose levels, concerns remain for individuals in high risk categories. In addition, cost and portability of CT and MRI machines can be prohibitive. In comparison, ultrasound can provide portable, low-cost, non-ionizing imaging. Previous clinical trials comparing ultrasound to CT were used to demonstrate qualitative and quantitative improvements of ultrasound using the Sandia technologies. Transverse leg images demonstrated much higher clarity and lower noise than is seen in traditional ultrasound images. An x-ray CT scan was provided of the same cross-section for comparison. The results of our most recent trials demonstrate the advantages of 3D ultrasound and motion compensation compared with 2D ultrasound. Metal objects can also be observed within the anatomy.

Computer Simulation↗
PubMed1997

Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis.

OBJECTIVE: To determine whether patients with ankylosing spondylitis (AS) and patients with rheumatoid arthritis (RA) from Japan have antibodies to Klebsiella pneumoniae and Proteus mirabilis and to assess whether such antibodies are activated against peptides sharing sequences with HLA-B27. METHODS: Serum samples from 152 Japanese patients, 52 with AS, 50 with RA, and 50 healthy controls, were tested against 3 bacteria (K. pneumoniae, P. mirabilis, and Escherichia coli) and 3 synthetic peptides (HLA-B27, pullulanase-D, and scrambled pullulanase-D control peptide) by ELISA under coded conditions. Samples were tested for elevations in IgG, IgA, and IgM antibody classes in patients with active AS or RA, in patients with RA with probable disease, and in patients with inactive AS. Disease activity was determined by an elevated serum C-reactive protein (> 10 mg/l) level and elevated erythrocyte sedimentation rate (> 20 mm/h). RESULTS: Patients with active AS showed specific elevations in serum IgA antibody levels against K. pneumoniae compared to patients with RA and controls (p < 0.001). No such elevation was seen in the IgG and IgM antibody classes. Patients with inactive AS showed no elevation in any class of antibody against K. pneumoniae compared to controls or patients with RA. Patients with active or probably active RA showed significant elevations in IgG antibody levels against P. mirabilis compared to AS and controls (p < 0.001). Patients with AS (active or inactive), RA (active or probably active), and controls showed no elevations in any antibody class to E. coli. Both active and inactive AS patients had specific autoantibodies against HLA-B27 peptide compared to patients with RA and controls (active AS: IgG, IgA, IgM, p < 0.001; inactive AS: IgG and IgA, p < 0.001). Patients with active AS had IgG and IgA antibodies against pullulanase-D peptide, which contains a sequence that cross reacts with HLA-B27 compared to controls (p < 0.001). CONCLUSION: These results provide the first evidence of AS and RA patients in Japan having specific elevations of antibody to K. pneumoniae and P. mirabilis, respectively. This suggests that K. pneumoniae in AS and P. mirabilis in RA may play a role in triggering and/or exacerbating these diseases.

Adult↗
PubMed1997

Nonstriatal dopamine D1 receptors regulate striatal acetylcholine release in vivo.

The role of dopamine (DA) D1 receptors in the regulation of acetylcholine (ACh) release in the striatum was studied using in vivo microdialysis in freely moving rats. Systemic administration of the full D1 DA receptor agonist A-77636 (4 micromol/kg) increased striatal ACh release by 53% above the base line and decreased DA release by 33%. Local application of A-77636 (10 and 100 microM) by reverse dialysis was without effect on either striatal ACh or DA release. Systemic administration of the D1 DA receptor antagonist SCH 23390 (0.74 micromol/kg) or SCH 39166 (1.42 micromol/kg) blocked the stimulation of striatal ACh release produced by systemic A-77636 (4 micromol/kg). Local perfusion of either SCH 23390 or SCH 39166 did not decrease basal ACh release. Furthermore, when applied locally via the dialysis probe, SCH 23390 (12 microM) or SCH 39166 (50 microM) failed to attenuate the stimulation of striatal ACh release produced by systemic A-77636. Similarly, d-amphetamine (5.42 micromol/kg)-induced increases in striatal ACh release were not modified by simultaneous local perfusion with SCH 39166 (50 microM). These findings are consistent with the hypothesis that D1 receptor activation stimulates ACh release in the striatum. However, because local application of D1 receptor agonists and antagonists fail to influence ACh release, the relevant D1 receptors are not located in the striatum. The use of unphysiological dialysis conditions (high concentrations of acetylcholinesterase (AChE) inhibitors, high Ca++ concentrations and an absence of Mg++ in the perfusion fluid) may account for some earlier suggestions that local D1 receptors regulate ACh release in the striatum.

Acetylcholine↗
PubMed1997

The role of interleukin-2, interleukin-12, and dendritic cells in cancer therapy.

PURPOSE: Recombinant interleukin-2 (rIL-2) administration can mediate regression of solid tumors in patients with melanoma and renal cell carcinoma. A better understanding of the mechanisms of rIL-2-mediated antitumor effects has led to the investigation of novel immunotherapeutic approaches. Two approaches that appear promising include administration of antigen-pulsed dendritic cells (DC) and administration of DC or genetically engineered fibroblasts expressing human interleukin-12 (IL-12). The rationale for these immunotherapeutic approaches and preliminary clinical studies are presented. PATIENTS AND METHODS: We have conducted a pilot study to evaluate the feasibility of treating melanoma patients with peptide-pulsed DC. Six melanoma patients received 1 to 3 x 10(6) DC pulsed with synthetic melanoma antigenic peptides. The peptide-pulsed DC were infused weekly for 4 weeks. We have also treated 32 patients in a phase I/II trial with IL-12-producing fibroblasts. Patients received escalating doses of cells weekly for 4 weeks, which produced quantities of IL-12 ranging from 10 ng to 9 micrograms/24 hours. RESULTS: Infusion of melanoma peptide-pulsed DC produced a complete response in one patient, and significant T-cell and DC infiltration of melanoma lesions was observed. Lesional and regional responses have been observed in patients with melanoma, head and neck carcinoma, and breast cancer who received intralesional injections of IL-12-producing fibroblasts. Phase II studies of this approach are planned and will be initiated in the next few months. CONCLUSIONS: These studies confirm the feasibility of these novel immunotherapeutic approaches and demonstrate their potential antitumor activity. These approaches may be effective in patients with metastatic melanoma and other solid tumors, and they may ultimately be used to improve the efficacy of rIL-2-based immunotherapy.

Carcinoma, Renal Cell↗
PubMed1997

Evaluation of three rapid RNA extraction reagents: relevance for use in RT-PCR's and measurement of low level gene expression in clinical samples.

Although peripheral blood and bone marrow are usually readily available from patients, present techniques of RNA extraction are tedious, require millilitres of starting material and removal of red blood cells before RNA purification. Further, successful reverse transcriptase polymerase chain reaction (RT-PCR) amplification requires the removal of haemoglobin derivatives which interfere with the PCR process. Recently, one step rapid use reagents have become available, claiming to be useful for obtaining high quality RNA from microlitre quantities of whole blood drawn directly from the patient. Their use to date in clinical samples appears limited with little information in the literature documented. In an attempt to overcome this, we tested the Trizol-LS, RNA-STAT-50 and Ultraspec-3 reagents upon a statistically significant number of clinical isolates of fresh and cryopreserved peripheral blood, bone marrow, blood apheresis products and a breast cancer cell line (MCF7) in order to evaluate whether these methods could be applied to routine laboratory use in an RT-PCR method capable of detecting rare gene expression. Our findings showed that there was some variation in the quality of RNA extracted which was indicated by absorbance spectrophotometry at 260 and 280 nm. 1% agarose gel electrophoresis showed that each of these methods could yield total RNA capable of generating the signature 18S and 28S rRNA bands. Using the Kruskal-Wallis non-parametric anova test combined with Dunn's multiple comparison test, the only statistically significant difference (p<0.05) indicated that Trizol-LS was more reliable than RNA-STAT-50-LS and Ultraspec-3 at extracting RNA from fresh peripheral blood. RNA extracted with the Trizol-LS and RNA STAT-50 reagents was successfully amplified in a multiplex RT-PCR reaction for detection of the multi-drug resistance related genes MDR1, the multi-drug resistance related protein (MRP) and topoisomerase IIalpha. Low level MDR1 gene expression could be detected in frozen whole blood. However, PCR products were only seen when the anti-coagulant heparin was removed from all samples prior to cDNA production. RT-PCR amplification was not 100% successful with RNA extracted with Ultraspec-3 reagent. In conclusion, we found that the RNA extracted from whole blood with the Trizol-LS and the RNA-STAT-50 are suitable for use in clinically relevant molecular biology protocols that analyze rare event genes without further purification. Our results indicated that the Trizol-LS reagent was generally more consistent in obtaining a pure and sufficient quantity of RNA from patient material as shown by the mean result of purity and quantity in comparison to either Ultraspec-3 or RNA-STAT-50-LS reagents. Ultraspec-3 is not easily suited for direct use with whole blood products.

Evaluation Studies as Topic↗
PubMed1996

Diastereoselective synthesis of all four isomers of 3-(4-chlorophenyl) glutamic acid: identification of the isomers responsible for the potentiation of L-homocysteic acid-evoked depolarizations in neonatal rat motoneurons.

All four isomers of 3-(4-chlorophenyl)glutamic acid (5-8) were prepared by diastereoselective synthesis. Addition of (6S)-(+)-bis-lactim ether 15 to cis-4-chlorocinnamate 12 gave a mixture comprising mainly the (2R,3S)- and (2R,3R)-isomers 5 and 6, respectively (in a ratio of 56:40), while addition of (6R)-(-)-bis-lactim ether 16 to 4-chlorocinnamate 12 gave a mixture comprising mainly the (2S,3R)- and (2S,3S)-isomers 8 and 7, respectively (in a ratio of 56:42). The four stereoisomers (5-8) were therefore conveniently prepared by addition of either 3-lithio-(6S)- or -(6R)-bis-lactim ether (15 or 16, respectively) to 4-chlorocinnamate 12 and separation of the resultant mixtures of diastereoisomers (23-26) by flash silica gel chromatography. The absolute configurations of 6 and 7 were confirmed by X-ray crystallography. Both the (2S,3S)- and (2S,3R)-isomers (7 and 8, respectively) at a concentration of 100 microM significantly potentiated depolarizations induced by 10 microM L-homocysteic acid (L-HCA) (% control +/- sem: 130.4 +/- 3.6, n = 20 and 114.5 +/- 2.4, n = 11, respectively) while the (2R,3S)-isomer 5 significantly reduced L-HCA response amplitude (94.2 +/- 1.4, n = 9) and the (2R,3R)-isomer 6 was inactive. Experiments designed to compare the agonist-potentiating actions of 7 and 8 in the neonatal rat spinal cord with L-trans-pyrrolidine-2,4-dicarboxylic acid, the well-known L-Glu uptake inhibitor, provided additional evidence for the selective enhancement of depolarizations due to L-HCA and not those due to L-Glu. This selective action supports the existence of multiple excitatory amino acid uptake sites.

Animals↗
PubMed1996

A JNK signal transduction pathway that mediates morphogenesis and an immune response in Drosophila.

The Drosophila MAP kinase DJNK is a homolog of the mammalian c-Jun amino-terminal kinase (JNK). Mutations in the DJNK gene correspond to the complementation group basket. DJNK is phosphorylated and activated by the Drosophila MAP kinase kinase HEP. Substrates of DJNK include the transcription factor DJun. DJNK participates in multiple physiological processes. Exposure to endotoxic lipopolysaccharide initiates an insect immune response and leads to DJNK activation. In addition, embryos lacking DJNK are defective in dorsal closure, a process in which the lateral epithelial cells migrate over the embryo and join at the dorsal midline. These data demonstrate that the DJNK signal transduction pathway mediates an immune response and morphogenesis in vivo.

Alleles↗
PubMed1996

Structure of the CAP-DNA complex at 2.5 angstroms resolution: a complete picture of the protein-DNA interface.

The crystallographic structure of the CAP-DNA complex at 3.0 A resolution has been reported previously. For technical reasons, the reported structure had been determined using a gapped DNA molecule lacking two phosphates important for CAP-DNA interaction. In this work, we report the crystallographic structure of the CAP-DNA complex at 2.5 A resolution using a DNA molecule having all phosphates important for CAP-DNA interaction. The present resolution permits unambiguous identification of amino acid-base and amino acid-phosphate hydrogen bonded contacts in the CAP-DNA complex. In addition, the present resolution permits accurate definition of the kinked DNA conformation in the CAP-DNA complex.

Base Composition↗
PubMed1996

Buspirone augmentation of selective serotonin reuptake inhibitors (SSRIs) in social phobia.

We evaluated the efficacy of buspirone, in the augmentation of social phobic symptom response to the selective serotonin reuptake inhibitors (SSRIs). Ten patients meeting DSM-III-R criteria for generalized social phobia were studied. Patients obtaining only a partial response to an adequate trial of an SSRI, received buspirone in addition to the SSRI for 8 weeks in an open trial. Seven patients (70%) were considered responders (moderate or marked improvement) and 3 (30%) were considered nonresponders (minimal improvement or no change). This study provides clinical evidence suggesting that buspirone augmentation may be a useful clinical strategy in social phobic patients who show a partial response to an SSRI.

Adolescent↗
PubMed1996

Conditioned and unconditioned stimuli increase frontal cortical and hippocampal acetylcholine release: effects of novelty, habituation, and fear.

Recent evidence showing that basal forebrain cholinergic neurons with projections to the frontal cortex and hippocampus are activated by behaviorally salient stimuli suggests that these neurons are involved in arousal and/or attentional processes. We sought in the present experiments to test this hypothesis by examining whether unconditioned stimuli (a tone and flashing light) that normally increase cortical nad hippocampal acetylcholine (ACh) release would fail to do so after habituation (i.e., repeated presentation with no programmed consequences). In addition, the extent to which presentation of these stimuli would continue to increase ACh release when they had previously been paired with an aversive stimulus was investigated. Three experimental groups were used: habituation, novel stimuli, and conditioned fear. Subjects in each of these groups were placed in a training apparatus for twelve 200 min sessions. While the habituation group received extensive exposure to the tone and light during the training sessions, subjects in the novel stimuli group were placed in the apparatus but were never exposed to the tone or light during these sessions. The conditioned fear group was treated identically to the habituation group, with the addition that the tone and light were paired with footshock. On completion of these training schedules, all animals were implanted with microdialysis probes in the frontal cortex and hippocampus. Two days later, they were placed in the apparatus and the tone and light were presented to all subjects during microdialysis. In the novel stimuli group, the tone and light (unconditioned stimuli) produced significant increases in frontal cortical and hippocampal ACh release. Similarly, in the conditioned fear group, presentation of the tone and light (conditioned stimuli) also significantly increased ACh release in frontal cortex and hippocampus. In contrast, in the habituation group the tone and light failed to significantly enhance ACh release in either structure. During the test session, the tone and light elicited a variety of arousal- and fear-related behaviors in the novel stimuli and conditioned fear groups. In contrast, subjects in the habituation group generally failed to respond to these stimuli. These data indicate that cortically and hippocampally projecting basal forebrain cholinergic neurons are activated by conditioned and unconditioned stimuli that produce arousal in rats (novelty or conditioned fear). In contrast, presentation of these stimuli to habituated animals fails to enhance ACh release. These findings are consistent with a growing body of information indicating that ACh release in the cortex and hippocampus is reliably activated by behaviorally relevant stimuli. They also provide strong support for the hypothesis that cholinergic neurons in the basal forebrain are involved in arousal and/or attentional processes.

Acetylcholine↗
PubMed1996

Clinical and laboratory findings in four patients with the non-progressive hepatic form of type IV glycogen storage disease.

The classic clinical presentation for type IV glycogen storage disease (branching enzyme deficiency, GSD IV) is hepatosplenomegaly with failure to thrive occurring in the first 18 months of life, followed by progressive liver failure and death by age 5 years. Although there have been two patients without apparent liver progression previously reported, no long-term follow-up clinical data have been available. We present here the clinical spectrum of the non-progressive liver form of GSD IV in four patients, and long-term follow-up of the oldest identified patients (ages 13 and 20 years). None has developed progressive liver cirrhosis, skeletal muscle, cardiac or neurological involvement, and none has been transplanted. Branching enzyme activity was also measured in cultured skin fibroblasts from patients with the classic liver progressive, the early neonatal fatal, and the non-progressive hepatic presentations of GSD IV. The residual branching enzyme activity in the patients without progression was not distinguishable from the other forms and could not be used to predict the clinical course. Our data indicate that GSD IV does not always necessitate hepatic transplantation and that caution should be used when counselling patients regarding the prognosis of GSD IV. Patients should be carefully monitored for evidence of progression before recommending liver transplantation.

1,4-alpha-Glucan Branching Enzyme↗