Identification of two novel mutations, L105R and C342R, in Type I Gaucher disease.
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Adult↗
Biomedical subjects
K Wong
Publications and source records attributed to K Wong.
Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.
The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1-Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.
Actins↗
Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology.
BACKGROUND: Screening biomarkers for ovarian cancer are needed because of its late stage at diagnosis and poor survival. We used microarray technology to identify overexpressed genes for secretory proteins as potential serum biomarkers and selected prostasin, a serine protease normally secreted by the prostate gland, for further study. METHODS: RNA was isolated and pooled from three ovarian cancer cell lines and from three normal human ovarian surface epithelial (HOSE) cell lines. Complementary DNA generated from these pools was hybridized to a microarray slide, and genes overexpressed in the cancer cells were identified. Real-time quantitative polymerase chain reaction was used to examine prostasin gene expression in ovarian cancer and HOSE cell lines. Anti-prostasin antibodies were used to examine prostasin expression and to measure serum prostasin by an enzyme-linked immunosorbent assay in 64 case patients with ovarian cancer and in 137 control subjects. Previously determined levels of CA 125, an ovarian cancer marker, were available from about 70% of all subjects. All statistical tests were two-sided. RESULTS: Prostasin was detected by immunostaining more strongly in cancerous ovarian epithelial cells and stroma than in normal ovarian tissue. The mean level of serum prostasin was 13.7 microg/mL (95% confidence interval [CI] = 10.5 to 16.9 microg/mL) in 64 case patients with ovarian cancer and 7.5 microg/mL (95% CI = 6.6 to 8.3 microg/mL) in 137 control subjects (P<.001, after adjustment for the subject's age, year of collection, and specimen quality). In 14 of 16 case patients with both preoperative and postoperative serum samples, postoperative prostasin levels were statistically significantly lower than preoperative levels (P =.004). In 37 case patients with nonmucinous ovarian cancer and in 100 control subjects for whom levels of CA 125 and prostasin were available, the combination of markers gave a sensitivity of 92% (95% CI = 78.1% to 98.3%) and a specificity of 94% (95% CI = 87.4% to 97.7%) for detecting ovarian cancer. CONCLUSIONS: Prostasin is overexpressed in epithelial ovarian cancer and should be investigated further as a screening or tumor marker, alone and in combination with CA 125.
Adult↗
The complete sequence of the 1,683-kb pSymB megaplasmid from the N2-fixing endosymbiont Sinorhizobium meliloti.
Analysis of the 1,683,333-nt sequence of the pSymB megaplasmid from the symbiotic N(2)-fixing bacterium Sinorhizobium meliloti revealed that the replicon has a high gene density with a total of 1,570 protein-coding regions, with few insertion elements and regions duplicated elsewhere in the genome. The only copies of an essential arg-tRNA gene and the minCDE genes are located on pSymB. Almost 20% of the pSymB sequence carries genes encoding solute uptake systems, most of which were of the ATP-binding cassette family. Many previously unsuspected genes involved in polysaccharide biosynthesis were identified and these, together with the two known distinct exopolysaccharide synthesis gene clusters, show that 14% of the pSymB sequence is dedicated to polysaccharide synthesis. Other recognizable gene clusters include many involved in catabolic activities such as protocatechuate utilization and phosphonate degradation. The functions of these genes are consistent with the notion that pSymB plays a major role in the saprophytic competence of the bacteria in the soil environment.
Bacterial Proteins↗
The composite genome of the legume symbiont Sinorhizobium meliloti.
The scarcity of usable nitrogen frequently limits plant growth. A tight metabolic association with rhizobial bacteria allows legumes to obtain nitrogen compounds by bacterial reduction of dinitrogen (N2) to ammonium (NH4+). We present here the annotated DNA sequence of the alpha-proteobacterium Sinorhizobium meliloti, the symbiont of alfalfa. The tripartite 6.7-megabase (Mb) genome comprises a 3.65-Mb chromosome, and 1.35-Mb pSymA and 1.68-Mb pSymB megaplasmids. Genome sequence analysis indicates that all three elements contribute, in varying degrees, to symbiosis and reveals how this genome may have emerged during evolution. The genome sequence will be useful in understanding the dynamics of interkingdom associations and of life in soil environments.
Bacterial Adhesion↗
The search for autism's roots.
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Autistic Disorder↗
Erythropoietin and erythropoietin receptor expression in human cancer.
Erythropoietin (EPO) stimulates the growth of erythroblasts in the bone marrow (C. Lacombe and P. Mayeux, NEPHROL: DIAL: TRANSPLANT:, 14 (SUPPL: 2): 22-28, 1999). We report basal and hypoxia-stimulated expression of EPO and its receptor, EPOR, in human breast cancer cells, and we demonstrate EPO-stimulated tyrosine phosphorylation and the proliferation of these cells in vitro. In 50 clinical specimens of breast carcinoma, we report high levels of EPO and EPOR associated with malignant cells and tumor vasculature but not with normal breast, benign papilloma, or fibrocystic tissue. Hypoxic tumor regions display the highest levels of EPO and EPOR expression. Enhanced EPO signaling may contribute to the promotion of human cancer by tissue hypoxia.
Biopsy↗
A model of temperature transients in dental implants.
Dental implants provide a continuous interface between the oral environment and the deep core structures of the jaws. Implants and trans-mucosal superstructures are primarily metal and heat conduction occurs readily. A hypothetical heat conduction model is investigated to determine the ranges of temperature gradients that might occur in implants. This model showed that a 60 degrees C heat source will cause a heat front of > or = 47 degrees C to advance > 3 mm down an implant within one second. Oral temperature transients may be a factor in implant pathology.
Dental Implants↗
A general algorithm for optimal sampling schedule design in nuclear medicine imaging.
Optimal sampling schedule (OSS) is of great interest in biomedical experiment design, as it can improve the physiological parameter estimation precision and significantly reduce the samples required. A number of well designed algorithms and software packages have been developed, which deal with the instantaneous measurements at discrete times. However, in nuclear medicine tracer kinetic studies, the imaging systems, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), take measurements (images) based on continuous accumulation over time intervals. In this case, the existing algorithms cannot be used to design OSS so as to reduce the image frame numbers. In this paper, a general OSS design algorithm for the accumulative measurement is proposed. The potential usefulness of the algorithm is demonstrated by its designing OSS in [18F] fluoro-2-deoxy-D-glucose (FDG) studies with PET to estimate the local cerebral metabolic rate of glucose. The robustness of parameter estimation using the OSS with respect to intra-subject and inter-subject parameter variations is also presented.
Algorithms↗
Synthesis and evaluation of a macrocyclic bifunctional chelating agent for use with bismuth radionuclides.
The detailed synthesis of the bifunctional chelating agent 2-(p-isothiocyanatobenzyl)-1,4,7,10,13-pentaazacyclopentadecane-N,N',N",N"',N""-pentaacetic acid (BF_PEPA) is reported. This ligand was conjugated to monoclonal antibody B3 and the resultant immunoconjugate radiolabeled with (205,206)Bi. The in vivo stability of the radiolabeled immunoconjugate, and targeting characteristics were determined by biodistribution studies in A431 xenograft tumor-bearing mice sacrificed at 0.5, 1, 2, 4, and 24 hr. Results indicate that BF_PEPA appears to not be a suitable bifunctional chelating agent for sequestering isotopes of Bi(III) for radioimmunotherapy applications.
Animals↗
Temperature effect in the avian osteoclast resorption assay [corrected].
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Animals↗
Gene polymorphism in Netherton and common atopic disease.
Atopic dermatitis (AD) and asthma are characterized by IgE-mediated atopic (allergic) responses to common proteins (allergens), many of which are proteinases. Loci influencing atopy have been localized to a number of chromosomal regions, including the chromosome 5q31 cytokine cluster. Netherton disease is a rare recessive skin disorder in which atopy is a universal accompaniment. The gene underlying Netherton disease (SPINK5) encodes a 15-domain serine proteinase inhibitor (LEKTI) which is expressed in epithelial and mucosal surfaces and in the thymus. We have identified six coding polymorphisms in SPINK5 (Table 1) and found that a Glu420-->Lys variant shows significant association with atopy and AD in two independent panels of families. Our results implicate a previously unrecognized pathway for the development of common allergic illnesses.
Amino Acid Sequence↗
Acute effects of pulmonary artery banding in sheep on right ventricle pressure-volume relations: relevance to the arterial switch operation.
The first stage of the two-stage arterial switch operation (ASO) for transposition of the great arteries (TGA) is associated with depressed ventricular function and an unstable immediate post-operative course. It is unclear if this is because of the acute increase in afterload of the thin-walled, low-pressure ventricle by pulmonary artery banding (PAB). To determine the acute effects of afterload increase on the contractile function of thin-walled ventricles, we studied the right ventricular pressure-volume relations of seven sheep before and 30 min after PAB using combined pressure-conductance catheters during inflow reduction. Load independent indices of systolic and diastolic performance were derived from these relations. Pulmonary artery banding increased the mean ratio between right and left ventricular systolic pressure from 0.34 +/- 0.05 to 0.64 +/- 0.10, P < 0.05 (mean +/- SD). There were no significant changes in heart rate and end-systolic volume after banding although there was an incremental trend in the end-diastolic volume and stroke volume. Right ventricular output (530 +/- 163-713 +/- 295 mL min (-1), P < 0.05), slope of the end-systolic pressure-volume relation (ESPVR) (3.7 +/- 2.8-10.0 +/- 4.8 mmHg mL (-1), P < 0.05) and slope of the pre-load recruitable stroke work (PRSW) relation (9.6 +/- 1.8-15.0 +/- 3.1 mmHg, P < 0.05) were significantly increased indicating improved contractile state after banding. The diastolic function curve was unchanged after banding although the right ventricle (RV) was operating at a larger end-diastolic volume. Hence, the RV of sheep responded to acute pressure overload by demonstrating enhanced contractility and evidence of the Frank-Starling mechanism without associated change in right ventricular diastolic performance.
Animals↗
Comparison of sevoflurane-nitrous oxide anaesthesia with the conventional intravenous-inhalational technique using bispectral index monitoring.
Ninety-one patients were randomly allocated to one of two groups. Group A was induced with a single vital capacity breath of 6% (end-tidal) sevoflurane in nitrous oxide-oxygen (2 : 1 l.min-1), whereas group B was induced with intravenous fentanyl 1 microg.kg-1 + propofol 2 mg.kg-1 followed by nitrous oxide-oxygen (2 : 1 l.min-1) and sevoflurane. Induction was considered to have been achieved when the bispectral index value decreased to below 70. Mean induction time in group A (95.2 s, 95% CI 88.5-101.9 s) was longer than group B (70.3 s, 95% CI 66.3-74.3 s; p < 0.0001). Mild coughing was more common in group A, but relative hypotension was more common in group B. There was no difference in the emergence times. Thirty minutes after emergence, there was no difference in the incidence of adverse effects, with the exception of essentially mild abdominal pain which was more frequent in group A.
Adult↗
Influence of clenbuterol treatment during six weeks of chronic right ventricular pressure overload as studied with pressure-volume analysis.
OBJECTIVES: Chronic pressure overload cardiac hypertrophy produces ventricular dysfunction. There is evidence that clenbuterol, a beta(2)-adrenoceptor agonist, produces cardiac hypertrophy with preserved function in rodents. We sought to determine the cardiac hypertrophic effects of clenbuterol on the thin-walled ventricles of large animals undergoing chronic pressure overload by means of pulmonary artery banding. METHODS: Right ventricular pressure-volume loops were obtained in open-chest sheep before and after 6-1/2 weeks of pulmonary artery banding by using micromanometer conductance catheters. Animals were randomly assigned to treatment with either saline solution (n = 7) or clenbuterol (n = 8). Treatment was started immediately after pulmonary artery banding. RESULTS: Acute pulmonary artery banding increased the right ventricular systolic pressure equally in both groups (saline group, 23.9 +/- 3.3 to 48.1 +/- 9.7 mm Hg; clenbuterol group, 24.3 +/- 2.8 to 48.6 +/- 10.7 mm Hg [mean +/- standard deviation]). Six weeks of treatment produced no significant differences in the body weight, heart weight, heart/body weight ratio, right ventricular wall thickness, heart rate, and stroke volume between the groups. However, the slope of the end-systolic pressure-volume relation and the slope of the first derivative of the right ventricular developed pressure/end-diastolic volume relation were significantly increased when compared with baseline values in clenbuterol-treated animals but not in saline-treated animals. CONCLUSION: Clenbuterol treatment during pulmonary artery banding improves systolic function of the chronically pressure-overloaded right ventricle. This has important implications for the use of pharmacologic agents in modulating cardiac adaptation.
Adrenergic beta-Agonists↗
Breath-hold three-dimensional CT of the liver with multi-detector row helical CT.
PURPOSE: To compare image quality on transverse source images and coronal and sagittal reformations to determine the feasibility of using single-breath-hold three-dimensional liver computed tomography (CT) with multi-detector row helical CT in patients suspected of having hepatic metastases. MATERIALS AND METHODS: Fifty-three patients underwent the protocol. Coronal and sagittal reformations were constructed. Images were reviewed for duration of scan acquisition and length and adequacy of z-axis coverage. Reformations were scored for visualization of portal and hepatic vein branches, liver edge sharpness, cardiac pulsation and respiratory motion artifacts, noise due to mottle, and overall impression. RESULTS: Mean z-axis coverage was 207 mm +/- 33 (SD) (range, 145-280 mm), with a mean acquisition time of 10.96 seconds +/- 1.78 (range, 7.73-14.93 seconds). In 44 (83%) patients, the entire liver was imaged on a single helical scan. Artifact from cardiac motion was not identified on the transverse source images in any patient but was identified on coronal images in eight (15%) and on sagittal images in seven (13%). Similarly, noise due to mottle was not identified on the transverse source images but was identified on coronal images in seven (13%) patients and on sagittal images in six (11%). CONCLUSION: It is feasible to perform single-breath-hold three-dimensional liver CT with multi-detector row helical CT technology. Reformations provide a unique perspective with which to view the liver and may improve diagnostic capacity.
Adult↗
A standardized, uniform and universal dental chart for documenting state of dentition before anaesthesia.
It is vital to have adequate and precise documentation of the condition of a patient's dentition before commencing an anaesthetic. The incidence of dental damage during anaesthesia is not low. To the authors' knowledge, there is no standardized method used by anaesthetists to document the state of a patient's dentition. We propose the introduction of a standardized uniform dental chart to enable anaesthetists to accurately document the condition of their patients' teeth. This vital information can be easily obtained during the preanaesthetic assessment. With the increase in medical litigation and demands for adequate documentation, we believe this chart can become an invaluable part of every hospital's preanaesthetic assessment form. The dental chart is to be offered as a service to anaesthetists in the form of a copyright-free "Freeware" computer diskette or adhesive sticker and will be downloadable from the internet.
Adult↗
Prevertebral abscess with extension into the hip joint.
We present a case of a paravertebral abscess with extension into the hip joint. The presumed conduit of infection in this case is the iliopsoas bursa, which has been shown to provide direct communication between the retroperitoneal space and the hip joint in up to 15% of cadaveric specimens. The patient was treated with emergent open irrigation and debridement of the hip joint, as well as percutaneous drainage of the prevertebral abscess. The patient remains minimally symptomatic at the 2-year follow-up.
Abscess↗