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Biomedical subjects

J A Young

Publications and source records attributed to J A Young.

At least 19 recordsLinked to original sources
PubMed2003

Extramammary metastatic neoplasms in the breast: a cytomorphological study of 11 cases.

The occurrence of metastatic tumours in the breast is uncommon and it is crucial for cytologists to be aware and distinguish them cytologically from primary breast tumours in fine needle aspirates. In the present retrospective study of 11 cases, over a 20-year period, we discuss the cytological features of extramammary metastatic tumours in the breast. A brief attempt has been made to discuss the past literature. The 11 metastatic tumours included four haematolymphoid neoplasms, two melanomas, two metastatic sarcomas and three metastatic carcinomas. A prior clinical diagnosis of the primary tumour was obtained in seven cases. Immunohistochemistry or histology following a cytological diagnosis confirmed all the cases. The main objective of this study was to highlight the use of cytology and at the same time caution the cytologist to be aware of the clinical/imaging findings and if necessary to utilize immunohistochemical facilities to consider/rule out the possibility of metastatic tumour in the breast.

Adult↗
PubMed2003

Evaluation of tuberculosis contact investigations in California.

OBJECTIVE: To estimate the burden of tuberculosis (TB) contact investigations in California, assess outcomes and effectiveness, and identify performance gaps. METHODS: Aggregate program management reports were used to examine contact investigations conducted for pulmonary TB cases reported between 1 July 1999 and 30 June 2000 in California. Findings were compared to national objectives, and performance gaps were identified. Costs were estimated, and effectiveness of TB case detection and prevention was assessed. RESULTS: A total of 2032 acid-fast bacilli sputum smear-positive and sputum smear-negative/culture-positive cases was reported; 17774 contacts were elicited, and 15582 (88%) contacts were evaluated. TB disease and latent tuberculosis infection (LTBI) were diagnosed in 111 (<1%) and 4609 (30%) contacts, respectively; 1958 (43%) contacts with LTBI completed treatment. Costs of contact investigations were estimated at dollars 4.8 million; 81% of expected TB cases were detected, but only 35% of cases expected to occur within 2 years following the investigation were prevented. CONCLUSIONS: California's performance did not meet national objectives for contact evaluation or treatment completion; improved effectiveness of contact investigations in California is needed. Although analysis of existing contact investigation surveillance data provided a macro-level view of performance gaps, expanded surveillance data are required to inform interventions.

California↗
PubMed2002

Self-reported dietary habits, overall dietary quality and symptomatology of breast cancer survivors: a cross-sectional examination.

Little information is available about the relationship between quality of life of women who have survived breast cancer (specifically, symptoms including those of menopause and depression) and the quality of their diet. In this cross-sectional study, 117 women with known primary breast cancer completed a self-administered food frequency questionnaire (FFQ) reflecting usual diet during the past year, a Survey of Feelings and Attitudes using the Center for Epidemiologic Studies Depression scale (CES-D) and a survey that includes menopausal symptoms among others common to women with a history of breast cancer. When women's responses to the FFQ were scored using the Healthy Eating Index (HEI), most often diets were evaluated as those that 'need improvement' with a mean total HEI score of 67.2. With regard to the CES-D scores, study women averaged 9.5, with 19 women being classified as clinically depressed. HEI and CES-D scores were inversely related (p = -0.22, p = 0.02). A negative correlation was also observed between energy-adjusted calcium intakes and CES-D scores (p = -0.19, p = 0.04). Clinical depressed women had not only lower HEI scores and calcium intakes, but also lower grain and variety scores. Comparisons to national data for disease-free women and that available for those with breast cancer suggest that our study women consumed diets low in energy and dietary variety. Diet quality may be an important factor influencing the manifestation of depressive symptoms in breast cancer survivors or conversely, poorer diet quality may be an outcome of depression.

Breast Neoplasms↗
PubMed2002

Low vision services for vision rehabilitation in the United Kingdom.

AIM: Little is known about the distribution and methods of delivery of low vision services across the United Kingdom. The purpose of this study was to determine the type and location of low vision services within the UK. METHODS: Survey by means of a 29 point postal questionnaire, followed when necessary by a five point telephone questionnaire. All known potential providers of low vision services (n = 2539) including hospitals (n = 277), optician/optometry practices (n = 1683), social services (n = 177), voluntary groups (n = 190), specialist teachers (n = 205), and universities (n = 6) were surveyed. For each service provider, the type, magnitude, and geographical location were determined. The distribution of services across the United Kingdom and the ratio of providers to population density of people with a visual impairment were mapped using the Geographic Information System (GIS). RESULTS: Data were obtained on 1945 (77%) service providers: 1679 (66%) responded to the postal questionnaire and 266 (11%) to the telephone questionnaire. Of all respondents, 59% (n = 1135) offer some form of help to people with a visual disability, of which 26% (n = 497) only sell magnifiers and 33% (n = 638) provide low vision services. It is estimated that in total just under 155,000 low vision consultations are offered annually, the bulk of which are provided by hospital eye departments. The distribution was geographically uneven and there appears to be scarcity in some areas. CONCLUSION: When compared to the probable number of people with a visual impairment in the UK there are apparent inadequacies in service provision in terms of distribution, magnitude, and coordination. The results highlight a need to review current services.

Health Care Surveys↗
PubMed2001

Identification of the cellular receptor for anthrax toxin.

The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.

Amino Acid Sequence↗
PubMed2001

Roles of the C termini of alpha -, beta -, and gamma -subunits of epithelial Na+ channels (ENaC) in regulating ENaC and mediating its inhibition by cytosolic Na+.

The amiloride-sensitive epithelial Na(+) channels (ENaC) in the intralobular duct cells of mouse mandibular glands are inhibited by the ubiquitin-protein ligase, Nedd4, which is activated by increased intracellular Na(+). In this study we have used whole-cell patch clamp methods in mouse mandibular duct cells to investigate the role of the C termini of the alpha-, beta-, and gamma-subunits of ENaC in mediating this inhibition. We found that peptides corresponding to the C termini of the beta- and gamma-subunits, but not the alpha-subunit, inhibited the activity of the Na(+) channels. This mechanism did not involve Nedd4 and probably resulted from the exogenous C termini interfering competitively with the protein-protein interactions that keep the channels active. In the case of the C terminus of mouse beta-ENaC, the interacting motif included betaSer(631), betaAsp(632), and betaSer(633). In the C terminus of mouse gamma-ENaC, it included gammaSer(640). Once these motifs were deleted, we were able to use the C termini of beta- and gamma-ENaC to prevent Nedd4-mediated down-regulation of Na(+) channel activity. The C terminus of the alpha-subunit, on the contrary, did not prevent Nedd4-mediated inhibition of the Na(+) channels. We conclude that mouse Nedd4 interacts with the beta- and gamma-subunits of ENaC.

Amiloride↗
PubMed2001

Chromatographic separations as a prelude to two-dimensional electrophoresis in proteomics analysis.

Current methods of proteome analysis rely almost solely on two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) followed by the excision of individual spots and protein identification using mass spectrometry (MS) and database searching. 2-D PAGE is denaturing in both dimensions and, thus, cannot indicate functional associations between individual proteins. Moreover, less abundant proteins are difficult to identify. To simplify the proteome, and explore functional associations, nondenaturing anion exchange column chromatography was used to separate a soluble protein extract from Escherichia coli. Successive fractions were then analysed using 2-D PAGE and selected spots from both the gels for the start material and the fractionated material were quantified and identified by peptide mass fingerprinting using a MALDI-TOF mass spectrometer. Enrichments of up to 13-fold were attained for individual protein spots and peptide mass fingerprints were of significantly higher quality after chromatographic separation. The marked anomalies between predicted p/and column elution position contrasted with the almost perfect correlation with migration distance on isoelectric focusing (IEF) and were explored further for basic proteins.

Chromatography, Ion Exchange↗
PubMed2001

Laparoscopic peritoneal lavage in staging gastric and oesophageal cancer.

AIMS: Accurate staging of gastric, oesophageal and oesophagogastric cancer is essential to avoid unnecessary laparotomies in patients where only palliation is appropriate. This requires a multimodal approach utilizing endoscopy, computed tomography and laparoscopy. Previous authors have found that the presence of free peritoneal tumour cells (FPTCs) detected at laparoscopy or laparotomy confers a poorer prognosis. However, various methods of peritoneal lavage are described. The aim of this study was to evaluate the prognostic value of our technique of peritoneal lavage. MATERIALS AND METHODS: 88 staging laparoscopies with peritoneal lavage were carried out between March 1997 and February 1999 on patients eligible for attempted curative resection of a gastric, oesophageal or oesophagogastric cancer. During laparoscopy the pelvis was irrigated with 200 ml of normal saline, with 100 ml aspirated and examined cytologically. Patients were followed-up until September, 1999. RESULTS: 11 patients had FPTC-positive cytology with a median survival following laparoscopy of 122 days (95% CI 82-161) with only a single patient surviving more than one year. In the FPTC-negative group, median survival was 378 days (95% CI 256,-). Log-rank Chi(2)=16.7, P<0.001. CONCLUSIONS: The presence of FPTCs detected by our technique is a contraindication to attempted curative resection - palliation only (medical or surgical) is appropriate.

Adult↗
PubMed2001

Effect of acutely increased left ventricular afterload on work output from the right ventricle in conscious dogs.

OBJECTIVE: To determine the effect of acute increments in left ventricular afterload on the stroke work output of the right ventricle in vivo. METHODS: After pharmacologic attenuation of autonomic reflexes, left and right ventricular pressure-volume data were obtained in 9 conscious dogs during vena caval occlusions performed before and during aortic constriction. RESULTS: The relationship between right ventricular stroke work and end-diastolic volume during vena caval occlusion was highly linear (r = 0.97 +/- 0.02), but the slope decreased by 20% +/- 13% during aortic constriction sufficient to increase left ventricular mean ejection pressure by 25% +/- 14% (P <.05). The volume-axis intercept remained constant. Similarly, the slope of the linear relationship between right ventricular free wall regional segment work and end-diastolic segment length declined by 22% +/- 10% during aortic constriction (P <.05), without significant change in the length-axis intercept. The reduction in both global and regional right ventricular stroke work at any given preload with increased left ventricular afterload was due entirely to decreased right ventricular stroke volume and free wall shortening, because right ventricular mean ejection pressure was unchanged. Additional experiments were performed in 5 open-chest dogs to produce a greater reduction in left ventricular free wall shortening than observed with aortic constriction by transient constriction of the left circumflex coronary artery. However, this intervention had no effect on right ventricular free wall segment work output. CONCLUSION: Increased left ventricular afterload decreases global and regional right ventricular stroke work at any given preload, a direct, negative systolic ventricular interaction.

Acute Disease↗
PubMed2001

Robotic surgical training in an academic institution.

OBJECTIVE: To detail robotic procedure development and clinical applications for mitral valve, biliary, and gastric reflux operations, and to implement a multispecialty robotic surgery training curriculum for both surgeons and surgical teams. SUMMARY BACKGROUND DATA: Remote, accurate telemanipulation of intracavitary instruments by general and cardiac surgeons is now possible. Complex technologic advancements in surgical robotics require well-designed training programs. Moreover, efficient robotic surgical procedures must be developed methodically and safely implemented clinically. METHODS: Advanced training on robotic systems provides surgeon confidence when operating in tiny intracavitary spaces. Three-dimensional vision and articulated instrument control are essential. The authors' two da Vinci robotic systems have been dedicated to procedure development, clinical surgery, and training of surgical specialists. Their center has been the first United States site to train surgeons formally in clinical robotics. RESULTS: Established surgeons and residents have been trained using a defined robotic surgical educational curriculum. Also, 30 multispecialty teams have been trained in robotic mechanics and electronics. Initially, robotic procedures were developed experimentally and are described. In the past year the authors have performed 52 robotic-assisted clinical operations: 18 mitral valve repairs, 20 cholecystectomies, and 14 Nissen fundoplications. These respective operations required 108, 28, and 73 minutes of robotic telemanipulation to complete. Procedure times for the last half of the abdominal operations decreased significantly, as did the knot-tying time in mitral operations. There have been no deaths and few complications. One mitral patient had postoperative bleeding. CONCLUSION: Robotic surgery can be performed safely with excellent results. The authors have developed an effective curriculum for training teams in robotic surgery. After training, surgeons have applied these methods effectively and safely.

Academic Medical Centers↗
PubMed2001

Targeting avian leukosis virus subgroup A vectors by using a TVA-VEGF bridge protein.

Previously, we have demonstrated that bridge proteins comprised of avian leukosis virus (ALV) receptors fused to epidermal growth factor (EGF) can be used to selectively target retroviral vectors with ALV envelope proteins to cells expressing EGF receptors. To determine whether another type of ligand incorporated into an ALV receptor-containing bridge protein can also function to target retroviral infection, the TVA-VEGF110 bridge protein was generated. TVA-VEGF110 consists of the extracellular domain of the TVA receptor for ALV subgroup A (ALV-A), fused via a proline-rich linker peptide to a 110-amino-acid form of vascular endothelial growth factor (VEGF). This bridge protein bound specifically to its cell surface receptor, VEGFR-2, and efficiently mediated the entry of an ALV-A vector into cells. These studies indicate that ALV receptor-ligand bridge proteins may be generally useful tools for retroviral targeting approaches.

Avian Leukosis Virus↗
PubMed2001

Two functionally distinct forms of a retroviral receptor explain the nonreciprocal receptor interference among subgroups B, D, and E avian leukosis viruses.

Subgroups B, D, and E avian leukosis viruses (ALV-B, -D, and -E) share the same chicken receptor, TVB(S1), a tumor necrosis factor receptor (TNFR)-related protein. These viruses, however, exhibit nonreciprocal receptor interference (NRI): cells preinfected with ALV-B or ALV-D are resistant to superinfection by viruses of all three subgroups, whereas those pre-infected by ALV-E are resistant only to superinfection by other subgroup E viruses. In this study, we investigated the basis of this phenomenon by characterizing the interaction of TVB(S1) with ALV-B Env or ALV-E Env. Sequential immunoprecipitation analysis using surface envelope immunoglobulin fusion proteins revealed the existence of two separate types of TVB(S1) that are encoded by the same cDNA clone. One form, designated the type 1 receptor, is specific for ALV-B and ALV-E. The other form, the type 2 receptor, is specific for ALV-B. We show that a protein consisting of only the first and second extracellular cysteine-rich domains of TVB(S1) is capable of forming both receptor types. However, the third extracellular cysteine-rich domain is required for efficient formation of the type 1 receptor. We also demonstrate that heterogeneous N-linked glycosylation cannot explain the difference in activities of the two receptor types. The existence of two types of TVB(S1) explains the NRI pattern between ALV-B and -E: subgroup B viruses establish receptor interference with both receptor types, whereas subgroup E viruses interfere only with the type 1 receptor, leaving the type 2 receptor available to mediate subsequent rounds of ALV-B entry. The formation of a TVB receptor type that is specific for cytopathic ALV may also have important implications for understanding how some subgroups of ALV cause cell death.

Amino Acid Sequence↗
PubMed2000

Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein.

Avian leukosis virus (ALV) has been used as a model system to understand the mechanism of pH-independent viral entry involving receptor-induced conformational changes in the viral envelope (Env) glycoprotein that lead to membrane fusion. Here, we report the unexpected finding that ALV entry depends on a critical low pH step that was overlooked when this virus was directly compared to the classical pH-dependent influenza A virus. In contrast to influenza A virus, receptor interaction plays an essential role in priming ALV Env for subsequent low pH triggering. Our results reveal a novel principle in viral entry, namely that receptor interaction can convert a pH-insensitive viral glycoprotein to a form that is responsive to low pH.

Avian Leukosis Virus↗
PubMed2000

Influenza virus inhibits amiloride-sensitive Na+ channels in respiratory epithelia.

Many pathogens causing diarrhea do so by modulating ion transport in the gut. Respiratory pathogens are similarly associated with disturbances of fluid balance in the respiratory tract, although it is not known whether they too act by altering epithelial ion transport. Here we show that influenza virus A/PR/8/34 inhibits the amiloride-sensitive Na(+) current across mouse tracheal epithelium with a half-time of about 60 min. We further show that the inhibitory effect of the influenza virus is caused by the binding of viral hemagglutinin to a cell-surface receptor, which then activates phospholipase C and protein kinase C. Given the importance of epithelial Na(+) channels in controlling the amount of fluid in the respiratory tract, we suggest that down-regulation of Na(+) channels induced by influenza virus may play a role in the fluid transport abnormalities that are associated with influenza infections.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Band-shaped and whorled microcystic dystrophy of the corneal epithelium.

OBJECTIVE: To report the clinical, histopathologic, and electron microscopic features of band-shaped and whorled microcystic corneal epithelial dystrophy. DESIGN: Two interventional case reports. PARTICIPANTS: Two patients, two eyes. INTERVENTION: The involved area of corneal epithelium was scraped from each cornea. RESULTS: Histopathologic examination showed microscopic vacuoles in the epithelial cytoplasm in both cases. Electron microscopic examination revealed mainly empty cytoplasmic vacuoles with scant nonspecific osmophilic material. The process recurred clinically in one patient. Changes in corneal topography are documented in one patient. CONCLUSION: Clinical findings and pathologic studies seem nearly identical to those in the original report. No pattern of systemic disorder or medication use was found. The cause of this condition remains unknown.

Aged↗