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Biomedical subjects

A Lee

Publications and source records attributed to A Lee.

At least 199 records · Page 11Linked to original sources
PubMed2000

Therapeutic immunization against Helicobacter pylori infection in the absence of antibodies.

Helicobacter pylori is an important human pathogen. Prophylactic immunization with bacterial antigen plus an adjuvant protects mice against challenge with live H. pylori. Surprisingly, it was found that immunizations of mice already infected with Helicobacter also influenced bacterial colonization. This concept of therapeutic immunization is a novel phenomenon. Because H. pylori lives in the lumen of the stomach, it was initially hypothesized that the protective mechanism would involve induction of secretory IgA. However, work with knockout mice has demonstrated that prophylactic immunization is equally effective in mice deficient in IgA and even in microMT mice lacking B lymphocytes. Currently nothing is known about therapeutic vaccination and the effect of immunizing a host with an ongoing ineffective immune response. To address this, we infected B-cell deficient, microMT mice with H. pylori and therapeutically immunized them four times in 3 weeks with bacterial sonicate and cholera toxin adjuvant. These immunizations significantly reduced colonization by H. pylori. The antibody- negative status of the microMT mice was confirmed by ELISA. Thus, therapeutic immunization stimulates an immune response, which reduces H. pylori infection via a mechanism that is antibody independent. How this is achieved remains to be determined, but may well involve a novel immune mechanism.

Adjuvants, Immunologic↗
PubMed2000

Networking of three dimensional sonography volume data.

Three-dimensioned (3D) sonography enables the examiner to store, instead of copies from single B-scan planes, a volume consisting of 300 scan planes. The volume is displayed on a monitor in form of three orthogonal planes--longitudinal, axial and coronal. Translation and rotation facilitates anatomical orientation and provides any arbitrary plane within the volume to generate organ optimized scan planes. Different algorithms allow the extraction of different information such as surface, or bone structures by maximum mode, or fluid filled structures, such as vessels by the minimum mode. The volume may contain as well color information of vessels. The digitized information is stored on a magnetic optical disc. This allows virtual scanning in absence of the patient under the same conditions as the volume was primarily stored. The volume size is dependent on different, examiner-controlled settings. A volume may need a storage capacity between 2 and 16 MB of 8-bit gray level information. As such huge data sets are unsuitable for network transfer, data compression is of paramount interest. 100 stored volumes were submitted to JPEG, MPEG, and biorthogonal wavelet compression. The original and compressed volumes were randomly shown on two monitors. In case of noticeable image degradation, information on the location of the original and compressed volume and the ratio of compression was read. Numerical values for proving compression fidelity as pixel error calculation and computation of square root error have been unsuitable for evaluating image degradation. The best results in recognizing image degradation were achieved by image experts. The experts disagreed on the ratio where image degradation became visible in only 4% of the volumes. Wavelet compression ratios of 20:1 or 30:1 could be performed without discernible information reduction. The effect of volume compression is reflected both in the reduction of transfer time and in storage capacity. Transmission time for a volume of 6 MB using a normal telephone with a data flow of 56 kB/s was reduced from 14 min to 28 s at a compression rate of 30:1. Compression reduced storage requirements from 6 MB uncompressed to 200 kB at a compression rate of 30:1. This successful compression opens new possibilities of intra- and extra-hospital and global information for 3D sonography. The key to this communication is not only volume compression, but also the fact that the 3D examination can be simulated on any PC by the developed 3D software. PACS teleradiology using digitized radiographs transmitted over standard telephone lines. Systems in combination with the management systems of HIS and RIS are available for archiving, retrieval of images and reports and for local and global communication. This form of tele-medicine will have an impact on cost reduction in hospitals, reduction of transport costs. On this fundament worldwide education and multi-center studies becomes possible.

Algorithms↗
PubMed2000

Animal models of gastroduodenal ulcer disease.

Animal models have played a significant role in research that aims to understand peptic ulceration. Firstly, they have helped define basic mechanisms of gastric mucosal defence and repair. The basis for gastric injury following NSAID administration was facilitated by animal models that correlated well with disease in humans. In early studies, ulceration was induced by grossly damaging insults to the gastric mucosa that were unphysiological. With refinement these models provided a clearer appreciation of stress ulceration. The discovery of Helicobacter pylori (H. pylori), as the cause of most ulcers, resulted in a need to re-evaluate the early literature and to look for new models. To date, these have contributed little to our understanding of the pathogenesis of H. pylori-induced ulcer. A major aim of this chapter is to suggest that thorough understanding of the animal models of Helicobacter infection may provide important new insights, in particular the factors controlling gastritis, the essential precursor lesion of ulceration. Available models include primates, cats, guinea pigs, ferrets and pigs. The mouse models provide opportunity for identifying both essential bacterial and host factors. The most severe pathologies are seen in the H. pylori-infected Mongolian gerbil with ulcers being formed in most animals. This is likely to become the standard animal model for investigation of peptic ulcer disease.

Animals↗
PubMed2000

Lymphangioma of large intestine: report of ten cases with endoscopic and pathologic correlation.

BACKGROUND: Lymphangioma of the intestinal tracts is extremely rare and usually presents as a sessile or pedunculated polyp. The cause of these gross morphologic differences is unknown. The aim of this study was to investigate the characteristic histopathology of the colonic lymphangiomas in comparison with their endoscopic findings. METHODS: Ten colonic lymphangiomas, diagnosed and resected endoscopically between 1992 and 1999, were microscopically examined and immunohistochemically stained with CD31, CD34, Factor VIII-related antigen, and smooth muscle actin. RESULTS: The characteristic endoscopic finding was a transparent, fluctuating sessile (7 cases) or pedunculated (3 cases) polypoid mass with the color of normal colonic mucosa. Proliferative and dilated lymphatic tumor vessels were found in the colonic mucosa as well as in the submucosa in seven cases. In three pedunculated lymphangiomas, dilated lymphatics were exclusively restricted to the submucosa. The endothelial lining cells stained positively for both CD31 and Factor VIII-related antigen in all 10 cases tested, but most cases were negative for CD34. CONCLUSION: A pedicle does not exclude the endoscopic diagnosis of lymphangioma and there is a close correlation between its presence and histologic submucosal localization of dilated lymphatic vessels.

Adult↗
PubMed2000

An assessment of the effects of casemix funding on hospital utilisation: a Northern Territory perspective.

This article is concerned with the methodological issues of assessing the effects of casemix funding on hospital utilisation. Time-series analysis and intervention analysis are proposed to ascertain the effects. It was found there had been a decline in average length of stay and number of bed-days, an increase in weighted separations for teaching and non-teaching hospitals, and no apparent increase of costliness in terms of a comprehensive casemix index. No evidence of decline in quality of care can be established in terms of readmission rates. The long-term effects of casemix funding, and specific issues in terms of the funding model used, patients and cost shifting between hospital services and community health services, remain to be studied.

Diagnosis-Related Groups↗
PubMed2000

Performance of older depressed patients on two cognitive malingering tests: false positive rates for the Rey 15-item memorization and dot counting tests.

To our knowledge, no investigations have been undertaken to determine whether depression impacts performance on two commonly used tests to detect malingering of cognitive symptoms, the Rey 15-item Memorization Test and the Rey Dot Counting Test. This is a critical issue because of the high rate of depressive symptoms in patients with neurological conditions. It was hypothesized that depressed individuals, especially those with more severe depression, might be at risk for failing the tests, because these patients exhibit mild deficits in mental speed, visual perceptual/spatial skills, and visual memory, abilities required for successful completion of the malingering tests. However, examination of test performance in 64 older participants with major depression generally revealed very low false positive rates for most test scores, and severity of depression was unrelated to test scores. These results add to accumulating data supporting the validity of these cognitive malingering tests by documenting few false positive identifications.

Age Factors↗
PubMed2000

Monoclonal antibodies generated against recombinant ATM support kinase activity.

We report on the rapid generation of two monoclonal antibodies, ATM A16.35 and ATM D16.11, that bind to the kinase domain of mutated ataxia telangiectasia (ATM). These antibodies were generated against E. coli-expressed recombinant protein using the RIMMS strategy. We show that ATM A16.35 binds ATM by Western blot analysis, and ATM D16.11 forms immune complexes with native ATM in immunoprecipitations without neutralizing kinase activity.

Animals↗
PubMed2000

Multistep phosphorelay proteins transmit oxidative stress signals to the fission yeast stress-activated protein kinase.

In response to oxidative stress, eukaryotic cells induce transcription of genes required for detoxification of oxidants. Here we present evidence that oxidative stress stimuli are transmitted by a multistep phosphorelay system to the Spc1/Sty1 stress-activated protein kinase in the fission yeast Schizosaccharomyces pombe. The fission yeast mpr1(+) gene encodes a novel protein with a histidine-containing phosphotransfer domain homologous to the budding yeast Ypd1. Spc1 activation upon oxidative stress is severely impaired in the Deltampr1 mutant as well as in the mpr1HQ strain, in which the putative phosphorylation site Mpr1-His221 is substituted with glutamine. In response to oxidative stress, Mpr1 binds to the Mcs4 response regulator that functions upstream of the Spc1 cascade, suggesting that Mcs4 is a cognate response regulator for Mpr1. Unexpectedly, when exposed to hydrogen peroxide, Deltampr1 cells can induce the catalase gene ctt1(+), one of the transcriptional targets of the Spc1 pathway, and survive oxidative stress in the absence of significant Spc1 activation. We have found that Pap1, a bZIP transcription factor homologous to human c-Jun, can mediate induction of ctt1(+) expression upon oxidative stress independently of the Spc1 stress-activated protein kinase. These studies show that oxidative stress stimuli are transmitted by multiple pathways to induce specific gene expression.

Activating Transcription Factor 1↗
PubMed2000

Energy expenditure in acetaminophen-induced fulminant hepatic failure.

OBJECTIVE: To determine energy expenditure in critically ill patients suffering from acetaminophen-induced fulminant hepatic failure and compare it with values obtained in matched, healthy control subjects and in patients studied during the anhepatic period of elective liver transplantation. DESIGN: Prospective, controlled, observational study. SETTING: A ten-bed intensive therapy unit and a liver transplant unit at a University teaching hospital. PATIENTS AND SUBJECTS: Sixteen patients suffering from acetaminophen-induced fulminant hepatic failure who were sedated, paralyzed, and mechanically ventilated; 16 age-, gender-, and weight-matched, awake, healthy control subjects; and 16 patients with chronic liver disease, undergoing elective liver transplantation, who were studied during the anhepatic period of surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The mean energy expenditure was calculated in each case for a 30-min period, using indirect calorimetry. In the patients undergoing liver transplantation, measurements were performed after clamping the hepatic veins and recipient hepatectomy. Energy expenditure was markedly increased in the fulminant hepatic failure group (mean energy expenditure, 4.05 [SD 0.52] kJ x kg(-1) x hr(-1)), in comparison with healthy control subjects (mean, 3.44 [0.27] kJ x kg(-1) x hr(-1); mean difference, 18%; p < .001) and in comparison with patients during the anhepatic period of liver transplantation (mean, 3.15 [0.61] kJ x kg(-1) x hr(-1); mean difference, 29%; p < .001). These differences were even more pronounced when a correction factor for differences in core temperature was included in the calculation. Harris-Benedict predictions of energy expenditure were unreliable in the patients with acute liver failure. No correlations were found among energy expenditure and hemodynamic variables, the requirement for vasoconstrictors, or the presence of renal failure. CONCLUSIONS: Despite the loss of functioning liver cell mass, the metabolic rate is substantially increased in patients with acetaminophen-induced fulminant hepatic failure. This finding is consistent with the marked systemic inflammatory response, which accompanies acute hepatic failure. The Harris-Benedict equation is unreliable when an estimation of energy expenditure is required in patients with this condition.

Acetaminophen↗
PubMed2000

Expression of the Helicobacter pylori ureI gene is required for acidic pH activation of cytoplasmic urease.

ureI encodes an integral cytoplasmic membrane protein. It is present in the urease gene cluster of Helicobacter pylori and is essential for infection and acid survival, but its role is unknown. To determine the function of UreI protein, we produced H. pylori ureI deletion mutants and measured the pH dependence of urease activity of intact and lysed bacteria and the effect of urea on the membrane potential. We also determined ureI expression, urease activity, and the effect of urea on membrane potential of several gastric and nongastric Helicobacter species. ureI was found to be present in the genome of the gastric Helicobacter species and absent in the nongastric Helicobacter species studied, as determined by PCR. Likewise, Western blot analysis confirmed that UreI was expressed only in the gastric Helicobacter species. When UreI is present, acidic medium pH activation of cytoplasmic urease is found, and urea addition increases membrane potential at acidic pH. The addition of a low concentration of detergent raised urease activity of intact bacteria at neutral pH to that of their homogenates, showing that urease activity was membrane limited. No acidic pH activation or urea induced membrane potential changes were found in the nongastric Helicobacter species. The ureI gene product is probably a pH activated urea transporter or perhaps regulates such a transporter as a function of periplasmic pH.

Bacterial Proteins↗
PubMed2000

Dominant nonresponsiveness to Helicobacter pylori infection is associated with production of interleukin 10 but not gamma interferon.

Helicobacter pylori-induced gastritis is an essential precursor lesion for the development of peptic ulcers or gastric adenocarcinoma. We demonstrate that nonresponsiveness to H. pylori SS1 infection is dominantly inherited in mice. F(1) hybrid crosses between a nonresponder mouse and three responder strains all possessed the nonresponder phenotype. Secretion of interleukin-10 but not gamma interferon was associated with nonresponsiveness to infection.

Adenocarcinoma↗
PubMed2000

Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance.

The effects of simultaneous expression of several efflux pumps on antibiotic resistance were investigated in Escherichia coli and Pseudomonas aeruginosa. Several combinations of efflux pumps have been studied: (i) simultaneous expression of a single-component efflux pump, which exports antibiotics into the periplasm, in combination with a multicomponent efflux pump that accomplishes efflux directly into the external medium; (ii) simultaneous expression of two single-component pumps; and (iii) simultaneous expression of two multicomponent pumps. It was found that when efflux pumps of different structural types were combined in the same cell (the first case), the observed antibiotic resistance was much higher than that conferred by each of the pumps expressed singly. Simultaneous expression of pairs of single-component or multicomponent efflux pumps (the second and third cases) did not produce strong increases in antibiotic resistance.

Anti-Bacterial Agents↗
PubMed2000

Assessing effectiveness of treatment of depression in primary care. Partially randomised preference trial.

BACKGROUND: There is a mismatch between the wish of a patient with depression to have counselling and the prescription of antidepressants by the doctor. AIMS: To determine whether counselling is as effective as antidepressants for depression in primary care and whether allowing patients to choose their treatment affects their response. METHOD: A partially randomised preference trial, with patients randomised to either antidepressants or counselling or given their choice of either treatment. The treatment and follow-up were identical in the randomised and patient preference arms. RESULTS: There were 103 randomised and 220 preference patients in the trial. We found: no differences in the baseline characteristics of the randomised and preference groups; that the two treatments were equally effective at 8 weeks, both for the randomised group and when the randomised and patient preference groups for a particular treatment were combined; and that expressing a preference for either treatment conferred no additional benefit on outcome. CONCLUSIONS: These data challenge several assumptions about the most appropriate treatment for depression in a primary care setting.

Adolescent↗
PubMed2000

Development of chick axial mesoderm: specification of prechordal mesoderm by anterior endoderm-derived TGFbeta family signalling.

Two populations of axial mesoderm cells can be recognised in the chick embryo, posterior notochord and anterior prechordal mesoderm. We have examined the cellular and molecular events that govern the specification of prechordal mesoderm. We report that notochord and prechordal mesoderm cells are intermingled and share expression of many markers as they initially extend out of Hensen's node. In vitro culture studies, together with in vivo grafting experiments, reveal that early extending axial mesoderm cells are labile and that their character may be defined subsequently through signals that derive from anterior endodermal tissues. Anterior endoderm elicits aspects of prechordal mesoderm identity in extending axial mesoderm by repressing notochord characteristics, briefly maintaining gsc expression and inducing BMP7 expression. Together these experiments suggest that, in vivo, signalling by anterior endoderm may determine the extent of prechordal mesoderm. The transforming growth factor (beta) (TGFbeta) superfamily members BMP2, BMP4, BMP7 and activin, all of which are transiently expressed in anterior endoderm mimic distinct aspects of its patterning actions. Together our results suggest that anterior endoderm-derived TGFbetas may specify prechordal mesoderm character in chick axial mesoderm.

Activins↗
PubMed2000

Choice of breastfeeding and physicians' advice: a cohort study of women receiving propylthiouracil.

OBJECTIVE: To examine the gap between the current social/medical practice and the evidence-based recommendation in favor of breastfeeding during maternal propylthiouracil (PTU) therapy. DESIGN: Prospective, observational, cohort study. SUBJECTS: Women requiring PTU during pregnancy, and endocrinologists and family physicians in Ontario, Canada. INTERVENTIONS: Questionnaire. MAIN OUTCOME MEASURES: Women were interviewed postpartum regarding their choice of infant feeding method and relevant advice received from physicians. Physicians were questioned about their advice to nursing women receiving PTU. RESULTS: Of 78 women, 66 had live births. Thirty-six required PTU postpartum (group 1), and 30 did not (group 2). Thirty-six healthy women served as controls (group 3). Breastfeeding initiation rates for groups 1, 2, and 3 were 44%, 83%, and 83%, respectively. In group 1, 15 women who breastfed received advice from 22 physicians regarding breastfeeding (20 in favor, 1 against, and 1 equivocal). Eleven who formula fed received advice from 17 physicians (4 in favor, 12 against, and 1 equivocal). A logistic regression analysis of group 1 showed that physicians' advice was the only significant predictor of the woman's choice to breastfeed during PTU therapy (relative risk: 5.48; 95% confidence interval: 1.28-23.40). The physician survey showed that 44% of endocrinologists do not recommend breastfeeding during PTU therapy. CONCLUSIONS: A substantial proportion of the lactating patients on PTU still receive advice against breastfeeding from their physicians. Physicians' advice and attitudes toward breastfeeding during PTU therapy are a major factor in women's final decision to breastfeed. Physicians' compliance with evidence-based data will facilitate breastfeeding in this group.propylthiouracil, breastfeeding, decision-making.

Attitude of Health Personnel↗
PubMed2000

Tropomodulin and tropomyosin mediate lens cell actin cytoskeleton reorganization in vitro.

PURPOSE: To determine the role of the actin cytoskeleton regulatory proteins tropomyosin and tropomodulin (Tmod) in the reorganization of the actin cytoskeleton during lens epithelial cell differentiation. METHODS: Primary cultures of chick lens epithelial cells were allowed to differentiate in vitro to form lentoid bodies. Localization of F-actin, Tmod, and tropomyosin were determined by immunofluorescent staining followed by confocal microscopy. Tropomyosin and Tmod isoform expression was determined by immunoprecipitation and western blot analysis. RESULTS: In undifferentiated epithelial cells F-actin was organized in polygonal arrays of stress fibers and was also associated with the adherens belt. In contrast, F-actin in differentiated cells was predominantly associated with membranes in a reticular or fibrillar pattern and was organized in curvilinear fibrils in the cytoplasm. Tmod was not detected in the undifferentiated epithelial cells but was expressed upon cell differentiation and assembled into F-actin and non-F-actin structures. Tmod isoforms expressed in the lens cell cultures were identical with those expressed in the embryonic chick lens fiber cells. Tropomyosin was associated with the polygonal arrays of stress fibers in the undifferentiated epithelial cells and was recruited to cortical F-actin at the cell periphery during differentiation. This occurred coincident with a shift in tropomyosin isoform expression. CONCLUSIONS: Expression and sequential assembly of low-molecular-weight tropomyosin and Tmod into the cortical actin cytoskeleton of differentiated lens cells may help to reorganize the actin cytoskeleton during morphogenetic differentiation. Moreover, lens epithelial cell differentiation may include the generation of novel Tmod-containing, non-F-actin cytoskeletal structures.

Actins↗
PubMed2000

Which drugs are contraindicated during breastfeeding? Practice guidelines.

QUESTION: Many breastfeeding mothers are concerned about taking medications that might affect their babies. Are there any guidelines on which drugs are safe? ANSWER: Only a few drugs pose a clinically significant risk to breastfed babies. In general, antineoplastics, drugs of abuse, some anticonvulsants, ergot alkaloids, and radiopharmaceuticals should not be taken, and levels of amiodarone, cyclosporine, and lithium should be monitored.

Anticonvulsants↗