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Biomedical subjects

M M Walker

Publications and source records attributed to M M Walker.

At least 19 recordsLinked to original sources

Use and rationale of a multicompartment microcassette for site-specific biopsies of the prostate in a consecutive cohort of men.

The collection of prostate biopsies into individual or site-specific specimen containers has not been performed routinely because of concerns of time, cost and lack of additional clinical value. This report evaluates the first ever use of a multicompartment microcassette for the collection and processing of site-specific prostate biopsies.Site-specific prostate biopsies were taken in sequential men suspected to have prostate cancer and collected in a multicompartment microcassette, which holds six biopsies and fits within a standard specimen container. Estimates were made of the cost and time savings compared with biopsies collected in individual specimen containers. In 88 men evaluated, use of the multicompartment microcassette saved time (72% reduction) and cost (83% reduction) with the added ability of easy identification of the site of each prostate biopsy. The multicompartment microcassette is a convenient, time- and cost-effective container for the collection of site-specific prostate biopsies.

Biopsy, Needle↗

Is intestinal metaplasia of the stomach reversible?

Intestinal metaplasia (IM) of the stomach is a risk factor in developing intestinal-type gastric cancer and hence the question of reversibility is vital. There is emerging epidemiological evidence that with long term follow up, IM may be reversible although a combination of antioxidant agents and eradication of H pylori may be necessary to achieve this. The pathogenesis of IM is currently being elucidated and it is likely that a combination of bacterial, host, and environmental factors will be shown to lead to IM. In assessing gastric cancer risk, histochemical typing of IM will most probably be replaced by molecular markers.

Alleles↗

The value of 'mesothelium-associated' antibodies in distinguishing between metastatic renal cell carcinomas and mesotheliomas.

AIMS: Despite increasing usage of mesothelium-associated antibodies in diagnosis, a meta-analysis of studies analysing these antibodies in relation to distinguishing mesothelioma from renal cell carcinoma shows a paucity of published data. Given the clinical importance of elucidating this differential diagnosis, we compared the phenotypes of these two tumours using a panel of antibodies comprising recently described 'mesothelium-associated' antibodies and the more established 'epithelium-associated' antibodies. METHODS AND RESULTS: We applied an antibody panel comprising calretinin, cytokeratin (CK)5/6, thrombomodulin, carcinoembryonic antigen (CEA), BerEP4 and BCA225 to 37 cases of pleural mesotheliomas and 40 cases of renal cell carcinoma (27 primary tumours and 13 metastatic to the pleura). All mesotheliomas were either purely epithelioid or of mixed type. Cases of renal cell carcinoma were graded and classified as to cell type and architecture. For mesotheliomas, 0% stained for CEA, 16% for BerEP4, 83% for BCA225, 78% for CK5/6, 86% for thrombomodulin and 97% showed nuclear staining for calretinin. For renal cell carcinomas, 0% stained for CEA, 50% for BerEP4, 88% for BCA225, 5% for CK5/6, 32% for thrombomodulin and 10% showed nuclear staining for calretinin. CONCLUSION: Calretinin, CK5/6 and BerEP4 appear the most useful antibodies in helping to distinguish between renal cell carcinomas and mesotheliomas, although BerEP4 was not particularly sensitive for renal cell carcinomas. Thrombomodulin was not as specific as the other 'mesothelium-associated' antibodies in this study, reflecting how staining for mesothelium-associated antibodies varies in carcinomas from different primary sites, and such variations should be taken into account when assessing the differential diagnosis of mesothelioma. In cases where doubt remains over distinguishing metastatic renal cell carcinoma from mesothelioma, data from such a panel should be viewed with caution and assessed in association with clinical, imaging and morphological features.

Antibodies, Neoplasm↗

A novel method for assessing gastritis in the murine model demonstrates genetically determined variation in response to Helicobacter felis infection.

BACKGROUND: In murine Helicobacter infection it has been demonstrated that the degree of gastric mucosal inflammation is determined by mouse strain. This is a valuable tool for investigating genetic, immunological or bacterial determinants for the outcome of human Helicobacter infection. This study aims to devise a robust method to facilitate these investigations. MATERIALS AND METHODS: C57BL/6, BALB/c and (C57BL/6 x BALB/c) F1 mice were given 10(8)H. felis by gavage on days 1, 3 and 5 of the experiment Sections of the lesser and greater curve of stomach were examined at 12 weeks to assess active gastritis using a semi-quantitative and a quantitative method by counting neutrophils in glands in four zones of the mucosa. RESULTS: Semi-quantitative scoring for active inflammation, based on the Sydney System, was inadequate with little discrimination between strains. Quantifying the level of active inflammation, counting the number of neutrophils in inflamed gastric glands and taking the total number of neutrophils in three inflamed pits within each zone (cardia, body, transitional zone and antrum) showed clear differences between the two parental strains for the degree of active gastritis and furthermore, using this system the phenotype of the (C57BL/6 x BALB/c) F1 was found to be between the two parental extremes. CONCLUSIONS: This novel method provides a numerical value for active inflammation in the stomach that is accurate, reproducible and discriminatory.

Animals↗

Detection of submicroscopic magnetite particles using reflectance mode confocal laser scanning microscopy.

Light microscopy and transmission electron microscopy work at such different scales that some components of cells may be too small to detect using light microscopy but too dispersed among cells within tissues to be discovered using electron microscopy. We have used reflectance mode confocal laser scanning microscopy to detect single-domain magnetite crystals in both live and resin-embedded preparations of magnetotactic bacteria. We show that reflections from bacterial cells are uniquely associated with the magnetite, which underpins the magnetotactic response of the bacteria. En bloc viewing shows that relatively large volumes of material can be searched with sufficient resolution to enable detection of submicroscopic particles. The techniques reported here may be of interest to others wishing to detect submicroscopic objects dispersed in large volumes of tissue.

Bacteria↗

Magnetite-based magnetoreception.

Orientation, navigation, and homing are critical traits expressed by organisms ranging from bacteria through higher vertebrates. Sensory systems that aid such behavior have provided key selective advantages to these groups over the past 4 billion years, and are highly evolved; magnetoreception is no exception. Across many species and groups of organisms, compelling evidence exists that the physical basis of this response is tiny crystals of single-domain magnetite (Fe3O4). It is the opinion of the authors that all magnetic field sensitivity in living organisms, including elasmobranch fishes, is the result of a highly evolved, finely-tuned sensory system based on single-domain, ferromagnetic crystals.

Animals↗

Oral cimetidine gives effective symptom relief in painful bladder disease: a prospective, randomized, double-blind placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of oral cimetidine as a treatment for painful bladder disease (PBD, variously described as a 'symptom complex' of suprapubic pain, frequency, dysuria and nocturia in the absence of overt urine infection) by assessing symptom relief and histological changes in the bladder wall tissue components, compared with placebo. PATIENTS AND METHODS: The study comprised 36 patients with PBD enrolled into a double-blind clinical study with two treatment arms, i.e. oral cimetidine or placebo, for a 3-month trial. Patients were asked to complete a symptom questionnaire (maximum score 35), and underwent cystoscopy and bladder biopsy before treatment allocation. On completing treatment the patients were re-evaluated by the questionnaire and biopsy. The symptom scores and bladder mucosal histology were compared before and after treatment, and the results analysed statistically to assess the efficacy of cimetidine. RESULTS: Of the 36 patients recruited, 34 (94%) completed the study. Those receiving cimetidine had a significant improvement in symptoms, with median symptom scores decreasing from 19 to 11 (P < 0.001). Suprapubic pain and nocturia decreased markedly (P = 0.009 and 0.006, respectively). However, histologically the bladder mucosa showed no qualitative change in the glycosaminoglycan layer or basement membrane, or in muscle collagen deposition, in either group. The T cell infiltrate was marginally decreased in the cimetidine group (median 203 before and 193 after) and increased in the placebo group (median 243 and 250, P > 0.3 and > 0.2, respectively). Angiogenesis remained relatively unchanged. The incidence of mast cells and B cells was sporadic in both groups. CONCLUSIONS: Oral cimetidine is very effective in relieving symptoms in patients with PBD but there is no apparent histological change in the bladder mucosa after treatment; the mechanism of symptom relief remains to be elucidated.

Administration, Oral↗

Hemispheric processing characteristics for lexical decisions in adults with reading disorders.

The present study measured unilateral tachistoscopic vocal reaction times and error responses of reading-disordered and normally reading adults to single words and nonwords in a series of lexical decision tasks at two linguistic levels (concrete and abstract words). Analysis of variance on reaction times indicated that main effects of stimulus type, visual field, and the interaction of these variables were not significant for the reading-disordered group, but visual field and an interaction of visual field and stimulus type were for the normally reading adults. Error rate showed a significant interaction of stimulus x visual field for the reading-disordered group but not for the normal reading group. Post hoc tests showed significant differences in error rates between visual fields for concrete lexicon but not for abstract or nonsense lexicon for the reading-disordered group. These findings suggest a deficit in interhemispheric lexical transfer occurs for reading-disordered samples and suggest use of a callosal relay model wherein the left hemisphere is allocated responsibility for performing central operations underlying lexical decisions by adults with reading disorders.

Adolescent↗

Transfer of lexical information in adults with reading disorders.

This study was designed to test whether adults with reading disorders differ from adults with normal reading abilities in their interhemispheric transfer rates during a lexical decision task. Correlations of performance were completed between lexical decision vocal reaction times (msec.), interhemispheric reaction rates (RVF vocal reaction times-LVF vocal reaction times) and measures of decoding skills, including sight word decoding and phonological decoding for 20 adults with reading disorders and 20 with normal reading abilities. Following a series of Pearson product-moment correlations, the correlation between interhemispheric transfer time and sightword recognition was significant and negative for the adults with reading disorders. This value indicates a significant association between the direction of the interhemispheric transfer time times and sight-word recognition for reading-disordered adults. When correlations were negative (LVF) reaction times < RVF reaction times), stronger sight-word recognition scores were found. The correlation between interhemispheric transfer time and sight-word recognition was not significant for the normal reading adults. For both groups, the correlations between interhemispheric transfer time and phonological decoding were not significant so an association between phonological decoding and interhemispheric transfer time was not evident, The current findings suggest a strong relationship between reading proficiency and reaction times in completing the lexical decision task for the reading-disordered adults.

Adolescent↗

Magnetite defines a vertebrate magnetoreceptor.

The key behavioural, physiological and anatomical components of a magnetite-based magnetic sense have been demonstrated in rainbow trout (Oncorhynchus mykiss). Candidate receptor cells located within a discrete sub-layer of the olfactory lamellae contained iron-rich crystals that were similar in size and shape to magnetite crystals extracted from salmon. Here we show that these crystals, which mapped to individual receptors using confocal and atomic force microscopy, are magnetic, as they are uniquely associated with dipoles detected by magnetic force microscopy. Analysis of their magnetic properties identifies the crystals as single-domain magnetite. In addition, three-dimensional reconstruction of the candidate receptors using confocal and atomic force microscopy imaging confirm that several magnetic crystals are arranged in a chain of about 1 microm within the receptor, and that the receptor is a multi-lobed single cell. These results are consistent with a magnetite-based detection mechanism, as 1-microm chains of single-domain magnetite crystals are highly suitable for the behavioural and physiological responses to magnetic intensity previously reported in the trout.

Animals↗

The relationship between Helicobacter pylori motility, morphology and phase of growth: implications for gastric colonization and pathology.

To explore the relationship between Helicobacter pylori motility, morphology and phase of growth, bacteria were isolated from antral biopsies of patients with duodenal ulcer or non-ulcer dyspepsia, and grown in liquid medium in batch and continuous culture systems. Motilities and morphologies of H. pylori in different phases of growth were examined with a Hobson BackTracker and by transmission electron microscopy. Morphologies of bacteria grown in vitro were also compared with those of bacteria in antral biopsies from patients with non-autoimmune gastritis. H. pylori had poor motility in lag phase, became highly motile in mid-exponential phase and lost motility in the decline phase of growth. Motilities of bacteria in the same phase of growth from patients with duodenal ulcer or non-ulcer dyspepsia were not significantly different. In the mid/late-exponential phase of growth bacteria had helical morphologies and multiple polar flagella, typical of H. pylori in the gastric mucus layer. In the decline phase of growth bacteria shed flagella, and had precoccoidal or coccoidal morphologies. These findings support the view that helical and coccoidal H. pylori are in different phases of growth with different roles in gastric colonization, indicate that bacterial motility per se is unlikely to be a determinant of H. pylori pathology, and suggest that H. pylori in the antral mucus layer is in a state of continuous (exponential phase) growth.

Biopsy↗

Helicobacter pylori infection and the pathogenesis of duodenal ulceration.

Helicobacter pylori is a gram-negative spiral bacterium confined to the habitat of gastric-type epithelium. H. pylori causes duodenal ulceration by a cumulative effect of antral predominant gastritis with increased acid secretion, consequent gastric metaplasia in the duodenum (a site of further colonization by H. pylori), duodenitis, reduced duodenal bicarbonate secretion, and mucosal damage. Bacterial factors influence outcome. Major determinants are the production of a vacuolating toxin and the presence of CagA, an immunodominant product of a nonconserved gene cagA, a marker for the cag pathogenicity island that encodes virulence genes involved in induction of epithelial chemokine responses. In ulcer patients the mucosal immune response is polarized to a T-helper-1 (Th1) cell-mediated response, which may contribute to mucosal damage. Eradication of H. pylori restores acid output to normal. Loss of both acid and bacteria halts gastroduodenitis and allows ulcer healing. Gastric metaplasia does not regress in the short term.

Animals↗

Changes to mucins in uninvolved mucosa and at the tumour site in gastric adenocarcinoma of intestinal type.

1. Mucin histochemistry is markedly altered in the stomach in intestinal-type adenocarcinoma. To increase understanding of these changes we have examined the content and distribution of carbohydrate in mucus glycopolypeptides isolated from non-malignant antrum, and from the uninvolved gastric mucosa and tumour site of patients with this disease. 2. The content of carbohydrate declined by 12.6% (P = 0.02) in mucus glycopolypeptides from uninvolved gastric mucosa when compared with those from non-malignant antrum, and by a further 25.4% (P < 0.001) in mucus glycopolypeptides from the tumour site. The first of these changes was accompanied by a significant decrease in the number of carbohydrate chains/1000 amino acid residues, and a significant increase in the number of monosaccharide units in each carbohydrate chain. The second of these changes was accompanied by significant decreases in both the number of carbohydrate chains/1000 amino acid residues, and in the number of monosaccharide units in each carbohydrate chain. 3. The number of sulphated monosaccharide units/100 carbohydrate chains increased from a mean of 7.2 in mucus glycopolypeptides from non-malignant antrum to a mean of 27.2 (P < 0.001) in preparations from uninvolved gastric mucosa and 22.7 (P < 0.001) in preparations from the tumour site. 4. Evidence is presented that these structural changes to mucus glycopolypeptides from the malignant stomach are due to an abnormal mucin biosynthesis by metaplastic goblet cells and/or immature gastric-type mucous cells within the uninvolved mucosa, and immature mucous cells at the tumour site.

ABO Blood-Group System↗

Quantitative histopathology can aid diagnosis in painful bladder syndrome.

AIMS: To define the pathology of painful bladder syndrome using a morphometric method. METHODS: Bladder biopsy specimens from 31 patients with painful bladder syndrome and 11 controls were stained and examined at x260 magnification with the aid of a 100 square counting grid. Random counts of the different tissues and inflammatory components were made to ascertain whether constant differences occurred that could be used to define the pathology of this uncommon condition. RESULTS: In the lamina propria of painful bladder syndrome specimens, a significant increase was seen in the concentration of lymphocytes, T cells, and blood vessels; a decrease was seen in the number of fibroblasts, and no change was seen in the number of mast cells and macrophages. B cells were sporadic. The basement membrane in these specimens showed significant discontinuity and there was increased collagen deposition in the underlying muscle when compared with controls. CONCLUSION: Painful bladder syndrome exhibits constant histological features that may be used to aid diagnosis in this uncommon condition. Simple numerical cell/tissue measurement of this kind is also useful when treatment trials are considered, because objective statistical analysis (pretreatment and post-treatment) is possible without the need for expensive and complicated equipment.

Adult↗

Absence of toxicity of oats in patients with dermatitis herpetiformis.

BACKGROUND: People with gluten sensitivity should avoid foods containing wheat, rye, and barley, but there has been debate about whether they should avoid oats. Although patients with celiac disease have recently been shown to tolerate oats, less is known about the effects of oats on patients with dermatitis herpetiformis. METHODS: We studied seven men and three women (mean age, 58 years) with biopsy-confirmed dermatitis herpetiformis. They had followed a strict gluten-free diet for a mean of 15.8 years, which controlled their rash and enteropathy. The patients added oats that were not contaminated with gluten to their diets for 12 weeks (mean [+/-SD] daily intake, 62.5+/-10.8 g). RESULTS: None of the patients had any adverse effects. Serologic tests for antigliadin, antireticulin, and antiendomysial antibodies were negative before oats were introduced into the diet and after they were discontinued. Villous architecture remained normal: the mean (+/-SE) ratio of the height of villi to the depth of crypts was 3.59+/-0.11 before the diet and 3.71+/-0.09 afterward (normal, 3 to 5), and the mean enterocyte heights were 31.36+/-0.58 microm and 31.75+/-44 microm, respectively (normal range, 29 to 34). Duodenal intraepithelial lymphocyte counts all remained within normal limits (mean, 13.8+/-1.03 per 100 enterocytes before the diet and 14.2+/-1.2 per 100 enterocytes afterward; normal range, 10 to 30). Dermal IgA showed no significant changes. CONCLUSIONS: Patients with dermatitis herpetiformis can include moderate amounts of oats in their gluten-free diets without deleterious effects to the skin or intestine.

Adult↗

Magnetic orientation and the magnetic sense in arthropods.

The physical properties of the earth's magnetic field are summarized with the aim of emphasizing their significance as cues that can be exploited in orientational tasks. Past work has revealed magnetic orientation in vertebrates as well as invertebrates, including arthropods. The key finding to date has been that, as opposed to many vertebrates, the magnetic compass of arthropods responds to the polarity, rather than to the inclination of the earth's magnetic field. As in the case of vertebrates, the debate over how arthropods detect magnetic fields has yet to be resolved. Currently, evidence has been reported in support of a detection system based on magnetite crystals together with a variety of detection systems based on events occurring at the molecular level. Interactions between the magnetic and other compasses in orientation experiments suggest the existence of an area in the brain where spatial orientation information from magnetic and other stimuli converges. The slow advance of our knowledge on magnetic orientation in arthropods, as opposed to the much better understanding of magnetic orientation in vertebrates, arises from difficulties in identifying the appropriate behavioural contexts in which arthropods respond to magnetic fields in both laboratory and field situations. Arthropods thus present challenges not only in demonstrating magnetic orientation, but also in elucidating the sensory mechanisms involved in the perception of magnetic fields.

Animals↗

A clinicopathological approach to cystitis--recommendations for simplified pathology reporting.

OBJECTIVE: To assess the accuracy of histopathology reports of bladder biopsy specimens showing chronic cystitis and to develop a standard method of reporting in the form of a template which will aid both clinician and patient in the management of this condition. MATERIALS AND METHODS: Over a 4-year period, the reports of 134 bladder biopsy specimens diagnosed as chronic inflammation of the bladder were examined for clinical details, cystoscopy findings, pathology details and conclusions. Within each of these groups, the common terms were assessed for their relevance to the final outcome. RESULTS: The analysis of each part of these reports revealed no clinical details in 33%, no cystoscopy details in 26% and no histopathology conclusion in 20%. The commonest terms used were: macroscopic haematuria (25%) for clinical details; red patch/ inflamed (40%) for cystoscopic details, morphological site involved (65%) for pathology details; and mild chronic cystitis (37%) for the conclusions. Standardized criteria were devised and after reassessing the reports, 75% were considered to be accurate and complete. CONCLUSIONS: Overall, the histopathology reports examined were more than adequate for the clinicians' use but the spectrum of details provided did not add to the usefulness of the final report. By limiting the terms available, a more standardized report can be produced, benefiting both clinician and patient.

Adult↗