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Biomedical subjects

G Wang

Publications and source records attributed to G Wang.

At least 451 records · Page 25Linked to original sources

Radiologic volumetry on a personal computer with a stereologic method.

RATIONALE AND OBJECTIVES: There is no universally accepted way to estimate organ and tumor volumes, and manual tracing of the outline of an organ or tumor is tedious, time-consuming, and therefore not widely used. The authors developed a stereologic method for estimating organ and tumor volumes with a personal computer and evaluated its accuracy and efficiency with computed tomographic images. MATERIALS AND METHODS: CT images were obtained of a 200-cm3 phantom sphere, a normal liver, a normal spleen, a brain tumor, and a large abdominopelvic tumor. Volumes were estimated with a computer program developed on a personal computer. The estimated volumes were compared with those found with the manual tracing method, which was used as a standard of reference. The time to complete each procedure was recorded. RESULTS: When approximately 200 grid points were used, the volumes estimated with the computer were varied from the reference by 1.9%-4.5%. The volumes ranged from 51 to 2,679 cm3, and the time to estimate these ranged from 42 to 96 seconds. CONCLUSION: Stereologic estimation of organ and tumor volumes from cross-sectional images with a personal computer can be accurate and efficient at a relatively low cost.

Abdominal Neoplasms↗

Investigation of the 1994-5 Ukrainian Vibrio cholerae epidemic using molecular methods.

Thirty-seven Vibrio cholerae and four non-cholera Vibrio isolates from Ukraine, including strains from the epidemic of 1994-5, were analysed by molecular methods. Results from PFGE and ribotyping indicated that all Ukrainian toxigenic V. cholerae were closely related to each other and to an isolate from a patient from Pakistan. A non-toxigenic river water strain obtained during the height of the epidemic was more distantly related to these V. cholerae strains, while the Vibrio parahaemolyticus isolates and Vibrio alginolyticus isolate were not closely related to V. cholerae or each other. ERIC- and REP-PCR allowed the differentiation of strains identical by other methods. The results obtained confirm that the epidemic Ukrainian strains are most closely related to seventh pandemic strains from Asia and support a hypothesis that the Ukrainian epidemic of 1994-5 was caused by toxigenic environmental strains surviving since the time of the 1991 Ukrainian epidemic or before.

Cholera↗

Experimental System for X-ray Cone-Beam Microtomography

: A laboratory test of X-ray tomography employing a diverging beam of X-rays rather than the usual parallel X-ray beam is described. We chose to test and demonstrate the advantages of divergent beam tomography by imaging an extracted juvenile human premolar using an ordinary dental X-ray source and a cooled CCD camera. Experiments with a three-piece cover-glass sample and with the human tooth demonstrated that three-dimensional reconstruction can be achieved at 34 µm per pixel resolution employing an X-ray tube spot 800 µm in its smallest direction without requiring close contact with the fluorescent screen. Reconstruction of a 256 x 256 pixel single-plane image from 100 projection images took only 45 sec on a personal computer with a Pentium 166 MHz processor. We have also demonstrated a volume reconstruction of 256 x 256 x 256 voxels from the data. Successful extension of this work to submicrometer projection X-ray microscopy is predicted. Improved resolution of medical tomography is another possible application.

Journal Article↗

A T cell-independent antitumor response in mice with bone marrow cells retrovirally transduced with an antibody/Fc-gamma chain chimeric receptor gene recognizing a human ovarian cancer antigen.

In order to treat common cancers with immunotherapy, chimeric receptors have been developed that combine the tumor specificity of antibodies with T-cell effector functions. Previously, we demonstrated that T cells transduced with a chimeric receptor gene against human ovarian cancer were able to recognize ovarian cancer cells in vitro and in vivo. We now report that recipients of bone marrow cells transduced with these genes exhibited significant antitumor activity in vivo. Moreover, in vivo depletion of T cells in reconstituted mice did not affect antitumor activity, suggesting that other immune cells expressing the chimeric receptor gene may play an important role in tumor rejection.

Animals↗

Costimulatory molecules in Wegener's granulomatosis (WG): lack of expression of CD28 and preferential up-regulation of its ligands B7-1 (CD80) and B7-2 (CD86) on T cells.

T cells are most likely to play an important role in the pathogenesis of WG, and recently a predominant Th1 pattern of immune response has been demonstrated in granulomatous inflammation. Since the expression of costimulatory molecules has a significant impact on the cytokine profile and proliferation response of T cells, the goal of this study was to characterize the expression of costimulatory molecules (CD28, CTLA-4 (CD152), B7-1 (CD80), B7-2 (CD86)) on T cells, monocytes and B cells in WG, and to correlate the findings with clinical parameters such as disease activity, extent and therapy. WG patients (n = 24) and healthy controls (HC; n = 17) were examined for the expression of costimulatory molecules by fluorescence-activated cell sorter analysis, both in whole peripheral blood and after in vitro activation of T cells and antigen-presenting cells. Results were correlated with clinical data. The expression of CD28 on CD4+ and CD8+ cells was significantly lower in WG than in HC (CD28+ 81.4% in WG versus 97.9% of CD4+ cells (P < 0.0001); CD28+ 44.6% in WG versus 68.5% of CD8+ cells (P < 0.00001)), both in peripheral blood and after in vitro activation. A lower percentage of monocytes was B7-2+ in WG than in HC in peripheral blood, whereas no significant differences in the expression of B7-1 and B7-2 were observed after in vitro stimulation of monocytes and B cells. After in vitro activation a significantly higher percentage of B7-1+ and B7-2+ T cells was seen in WG. There was no significant difference in the CTLA-4 expression pattern between WG and HC. The percentage of CD28+ lymphocytes correlated negatively with the Disease Extent Index cumulated over the course of disease (r = -0.46, P = 0.03), indicating a more severe manifestation in patients with lower CD28 expression. Correlations with other clinical parameters such as activity or therapy were not seen. WG patients show a lack of CD28 expression on T cells and an unusual up-regulation of its ligands B7-1 and B7-2 on T cells after in vitro activation as well as a lower expression of B7-2 on freshly isolated monocytes compared with HC. These features might promote the Th1 cytokine pattern and thereby contribute to persistently high levels of immune activation in WG.

Adult↗

Expression of brain-derived neurotrophic factor protein in activated microglia of human immunodeficiency virus type 1 encephalitis.

The role of neurotrophic factors and their therapeutic potential have been investigated in various neurodegenerative disorders. In neurodegeneration associated with human immunodeficiency virus (HIV) infection, neuronal function and survival may be affected by abnormal neurotrophic regulation involving HIV-infected microglia and reactive astrocytes. To characterize the cellular localization of brain-derived neurotrophic factor (BDNF) and its high-affinity tyrosine kinase receptor, trkB, proteins in HIV-1 encephalitis, we examined post-mortem brains from patients with acquired immunodeficiency syndrome and brains from non-HIV-infected controls. Using double immunofluorescent confocal microscopy, we found that BDNF immunoreactivity was distributed in neocortical neuronal perikarya and neuritic processes, while in the striatum only neurites were BDNF-immunoreactive. Additionally, the striatum with HIV infection was characterized by BDNF immunoreactivity in infiltrating activated microglia/macrophages and multinucleated giant cells. Catalytic trkB receptor immunoreactivity was observed in neuronal perikarya in the neocortex and striatum, as well as in reactive astrocytes within HIV-infected regions. Our findings suggest that expression of BDNF by activated microglia in HIV-1 encephalitis may affect neuronal survival and astroglial response through corresponding trkB receptors.

AIDS Dementia Complex↗

Heat shock response enhances acid tolerance of Escherichia coli O157:H7.

Escherichia coli O157:H7 (O157) has unusual acid tolerance. The influence of heat shock on acid tolerance of O157 was studied. Seven strains of O157 and E. coli K-12 were tested for their ability to survive in minimum glucose medium (pH 2.5) at 37 degrees C. The survival of heat-shocked (10 min at 48 degrees C) cells was about 10-100 times greater compared with untreated cells depending on the strain. No significant difference (P > 0.05) for O157 strain 932 was observed between heat shock-induced and acid adaptation-induced (pH 5.0) acid tolerance. Chloramphenicol prevented heat shock-induced acid tolerance, indicating the requirement of newly synthesized protein(s). Two outer membrane proteins (OMP) (22 and 15 kDa) were synthesized within 10 min of heat shock and were expressed for at least 6 h by cells held at 37 degrees C. N-terminal amino acid sequence analysis suggested that the 22 kDa OMP is a component of an alkyl hydroperoxide reductase. This protein contains a redox active disulphide, which is probably involved in H+ transport. Results indicate that sublethal heat treatment of O157 cells substantially increases their tolerance to acidic conditions. This could have practical implications for foods that receive a mild heat treatment and rely on acid as a preservative.

Amino Acid Sequence↗

Pathological evidence of prolonged umbilical cord encirclement as a cause of fetal death.

A case is presented in which autopsy findings (deep groove around the fetal waist and buttock), and gross and microscopic umbilical cord and placental examination (linear ulcer of umbilical cord histologically rimmed by fetal epidermal implants with evidence of remote bleeding) established the diagnosis of umbilical cord encirclement as a cause of intrauterine fetal death despite the lack of prenatal or postnatal obstetrical evidence.

Adult↗

Wet litter and perches as risk factors for the development of foot pad dermatitis in floor-housed hens.

1. An experiment was conducted to determine whether different moisture levels of litter and perches with different hygienic conditions are involved in the manifestation of foot pad dermatitis in White Leghorn layers. 2. Four different treatments were compared: dry litter and dry perches; dry litter and wet perches; wet litter and dry perches; and wet litter and wet perches. Temperature, pH, air humidity and ammonia changes in the pens were monitored. 3. The mean prevalence of foot pad lesions in groups 1, 2, 3 and 4 was 17%, 13%, 49% and 48% respectively. The overall incidence of foot pad lesions in birds reared on dry litter was 38%, and in birds reared on wet litter 92%. 4. When the air temperature was above 20 degrees C, an increasing moisture content in the litter was associated with an increasing incidence of foot pad dermatitis. However, when the air temperature was below 20 degrees C there were no new cases of dermatitis in any of the 4 treatments. There were no significant differences in litter pH or ammonia between the 4 treatments when compared over the whole experiment. 5. Although the incidence of lesions was not significantly affected by the presence of wet perches, the area of the lesions tended to be in groups with wet patches than in groups with dry perches. 6. It is suggested that moisture and temperature are important contributing factors for the occurrence of foot pad dermatitis in laying hens. Wet perches may contribute to the severity of such lesions.

Animals↗

Effects of isoproterenol on blood-brain barrier permeability in rats.

This study was performed to examine whether the direct topical application of isoproterenol to the cerebral cortex could modify the blood-brain barrier (BBB) permeability and whether this effect could be blocked by Timolol, a beta-adrenergic receptor antagonist without a membrane stabilizing effect. After a craniotomy in each animal, a low-dose (10(-4) M, n = 6) or a high-dose (10(-3) M, n = 6) isoproterenol patch was placed on one cortex (Ipsilateral Cortex: IC) and a normal saline patch was placed on the other cortex (Control Cortex: CC). Another 6 animals were pretreated with Timolol 1.5 mg kg(-1) i.v. before the placement of high dose isoproterenol patches. The BBB transfer coefficient (Ki) was determined using 14C-alpha-aminoisobutyric acid. Mean arterial blood pressure decreased after low- and high-dose isoproterenol patches. The low- and high-dose of isoproterenol increased Ki by 58% (IC: 5.94+/-2.02, CC: 3.77+/-1.75 microl g min(-1)) and 66% (IC: 6.97+/-3.66, CC: 4.19+/-2.48 microl g min(-1)) respectively when compared to that of the corresponding CC. Pretreatment with Timolol prevented the increase of the Ki by a high-dose of isoproterenol (IC: 5.33+/-1.88, CC: 5.66+/-1.72 microl g min(-1)). Our data demonstrate that a direct application of a beta-adrenergic receptor agonist to the brain parenchyma increased the permeability of the BBB, and that this effect could be prevented with a beta-adrenoceptor antagonist.

Adrenergic beta-Agonists↗

Spiral CT image deblurring for cochlear implantation.

Cochlear implantation is the standard treatment for profound hearing loss. Preimplantation and postimplantation spiral computed tomography (CT) is essential in several key clinical and research aspects. The maximum image resolution with commercial spiral CT scanners is insufficient to define clearly anatomical features and implant electrode positions in the inner ear. In this paper, we develop an expectation-maximization (EM)-like iterative deblurring algorithm to achieve spiral CT image super-resolution for cochlear implantation, assuming a spatially invariant linear spiral CT system with a three-dimensional (3-D) separable Gaussian point spread function (PSF). We experimentally validate the 3-D Gaussian blurring model via phantom measurement and profile fitting. The imaging process is further expressed as convolution of an isotropic 3-D Gaussian PSF and a blurred underlying volumetric image. Under practical conditions, an oblique reconstructed section is approximated as convolution of an isotropic two-dimensional (2-D) Gaussian PSF and the corresponding actual cross section. The spiral CT image deblurring algorithm is formulated with sieve and resolution kernels for suppressing noise and edge artifacts. A typical cochlear cross section is used for evaluation, demonstrating a resolution gain up to 30%40% according to the correlation criterion. Physical phantoms, preimplantation and postimplantation patients are reconstructed into volumes of 0.1-mm cubic voxels. The patient images are digitally unwrapped along the central axis of the cochlea and the implanted electrode array respectively, then oblique sections orthogonal to the central axis formed. After deblurring, representation of structural features is substantially improved in all the cases.

Algorithms↗

GI tract unraveling with curved cross sections.

Gastrointestinal (GI) tract examination with spiral/helical computed tomography (CT) is currently performed by slice-based inspection of axial images. CT colography is a recent advance which allows an intraluminal visualization of the colon, similar to endoscopy. Various rendering algorithms have been developed with promising results, however navigation through the complex, tortuous anatomy of the colon can be time consuming in practice. In this paper, we propose an electrical-field-based method to unravel the convoluted colon, that is, to digitally straighten it with curved cross sections and flatten it over a plane. In our method, electrical charges are simulated along the central colon path. Curved cross sections are defined by the electrical force lines, and lead to consistent unraveling. It is demonstrated with image volumes of two patients that this technique produces a global planar view of complicated colon features with a potential for detection of polyps.

Algorithms↗

An iterative algorithm for X-ray CT fluoroscopy.

X-ray computed tomography fluoroscopy (CTF) enables image guidance of interventions, synchronization of scanning with contrast bolus arrival, and motion analysis. However, filtered backprojection (FB), the current method for CTF image reconstruction, is subject to motion and metal artifacts from implants, needles, or other surgical instruments. Reduced target lesion conspicuity may result from increased image noise associated with reduced tube current. In this report, we adapt the row-action expectation-maximization (EM) algorithm for CTF. Because time-dependent variation in images is localized during CTF, the row-action EM-like algorithm allows rapid convergence. More importantly, this iterative CTF algorithm has fewer metal artifacts and better low-contrast performance than FB.

Algorithms↗

Site-specific mutations in the 23S rRNA gene of Helicobacter pylori confer two types of resistance to macrolide-lincosamide-streptogramin B antibiotics.

Clarithromycin resistance in Helicobacter pylori is mainly due to A-to-G mutations within the peptidyltransferase region of the 23S rRNA. In the present study, cross-resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics (MLS phenotypes) has been investigated for several clinical isolates of H. pylori. Two major types of MLS resistance were identified and correlated with specific point mutations in the 23S rRNA gene. The A2142G mutation was linked with high-level cross-resistance to all MLS antibiotics (type I), and the A2143G mutation gave rise to an intermediate level of resistance to clarithromycin and clindamycin but no resistance to streptogramin B (type II). In addition, streptogramin A and streptogramin B were demonstrated to have a synergistic effect on both MLS-sensitive and MLS-resistant H. pylori strains. To further understand the mechanism of MLS resistance in H. pylori, we performed in vitro site-directed mutagenesis (substitution of G, C, or T for A at either position 2142 or 2143 of the 23S rRNA gene). The site-directed point mutations were introduced into a clarithromycin-susceptible strain, H. pylori UA802, by natural transformation followed by characterization of their effects on MLS resistance in an isogenic background. Strains with A-to-G and A-to-C mutations at the same position within the 23S rRNA gene had similar levels of clarithromycin resistance, and this level of resistance was higher than that for strains with the A-to-T mutation. Mutations at position 2142 conferred a higher level of clarithromycin resistance than mutations at position 2143. All mutations at position 2142 conferred cross-resistance to all MLS antibiotics, which corresponds to the type I MLS phenotype, whereas mutations at position 2143 were associated with a type II MLS phenotype with no resistance to streptogramin B. To explain that A-to-G transitions were predominantly observed in clarithromycin-resistant clinical isolates, we propose a possible mechanism by which A-to-G mutations are preferentially produced in H. pylori.

Anti-Bacterial Agents↗

Molecular typing of Borrelia burgdorferi sensu lato by randomly amplified polymorphic DNA fingerprinting analysis.

To study whether pathogenic clusters of Borrelia burgdorferi sensu lato strains occur, we typed 136 isolates, cultured from specimens from patients (n = 49) with various clinical entities and from ticks (n = 83) or dogs (n = 4) from different geographic regions, by randomly amplified polymorphic DNA (RAPD) fingerprinting with four arbitrary primers. The RAPD patterns were reproducible up to the 95% similarity level as shown in duplicate experiments. In these experiments the purified DNAs prepared on different days, from different colonies, and after various passages were used as templates. With an intergroup difference of 55%, the 136 strains could be divided into seven genetic clusters. Six clusters comprised and corresponded to the established species B. burgdorferi sensu stricto (n = 23), Borrelia garinii (n = 39), Borrelia afzelii (n = 59), Borrelia japonica (n = 1), Borrelia valaisiana (n = 12), and genomic group DN127 (n = 1). One strain from a patient with erythema migrans (EM) did not belong to any of the species or genomic groups known up to now. The RAPD types of B. burgdorferi sensu stricto, B. garinii, and B. afzelii isolates, which may give rise to human Lyme borreliosis (LB), were associated with their geographic origins. A high degree of genetic diversity was observed among the 39 B. garinii strains, and six subgroups could be recognized. One of these comprised eight isolates from patients with disseminated LB only and no tick isolates. B. afzelii strains from patients with EM or acrodermatitis chronica atrophicans were not clustered in particular branches. Our study showed that RAPD analysis is a powerful tool for discriminating different Borrelia species as well as Borrelia isolates within species.

Animals↗

Genotypic characterization of clarithromycin-resistant and -susceptible Helicobacter pylori strains from the same patient demonstrates existence of two unrelated isolates.

Clarithromycin-susceptible and clarithromycin-resistant Helicobacter pylori isolates from the same patient were investigated for the mode of development and mechanism of clarithromycin resistance. The clarithromycin-resistant strain UA1182 harbors homozygous A-to-G mutations at position 2143 in both copies of the 23S rRNA gene and has a phenotype of resistance to clarithromycin and clindamycin but no significant resistance to streptogramin B. Pulsed-field gel electrophoresis patterns of NruI- and NotI-digested genomic DNA from the Clas and Clar isolates demonstrated that they are genetically distinct, suggesting that the development of clarithromycin resistance is not from the mutation of the existing Clas strain but from a completely new strain.

Anti-Bacterial Agents↗

Influence of cell polarity on retrovirus-mediated gene transfer to differentiated human airway epithelia.

Gene transfer with recombinant murine leukemia viruses (MuLV) provides the potential to permanently correct inherited lung diseases, such as cystic fibrosis (CF). Several problems prevent the application of MuLV-based recombinant retroviruses to lung gene therapy: (i) the lack of cell proliferation in mature pulmonary epithelia, (ii) inefficient gene transfer with a vector applied to the apical surface, and (iii) low titers of many retroviral preparations. We found that keratinocyte growth factor (KGF) stimulated proliferation of differentiated human tracheal and bronchial epithelia. Approximately 50% of epithelia divided in response to KGF as assessed by bromodeoxyuridine histochemistry. In airway epithelia stimulated to divide with KGF, high-titer ampho- and xenotropic enveloped vectors preferentially infected cells from the basal side. However, treatment with hypotonic shock or EGTA transiently increased transepithelial permeability, enhancing gene transfer with the vector applied to the mucosal surfaces of KGF-stimulated epithelia. Up to 35% of cells expressed the transgene after gene transfer. By using this approach, cells throughout the epithelial sheet, including basal cells, were targeted. Moreover, the Cl- transport defect in differentiated CF airway epithelia was corrected. These findings suggest that barriers to apical infection with MuLV can be overcome.

Bronchi↗

In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5.

We have evaluated the in vivo distribution of the major human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) coreceptors, CXCR4, CCR3, and CCR5, in both rhesus macaques and humans. T lymphocytes and macrophages in both lymphoid and nonlymphoid tissues are the major cell populations expressing HIV/SIV coreceptors, reaffirming that these cells are the major targets of HIV/SIV infection in vivo. In lymphoid tissues such as the lymph node and the thymus, approximately 1 to 10% of the T lymphocytes and macrophages are coreceptor positive. However, coreceptor expression was not detected on follicular dendritic cells (FDC) in lymph nodes, suggesting that the ability of FDC to trap extracellular virions is unlikely to be mediated by a coreceptor-specific mechanism. In the thymus, a large number of immature and mature T lymphocytes express CXCR4, which may render these cells susceptible to infection by syncytium-inducing viral variants that use this coreceptor for entry. In addition, various degrees of coreceptor expression are found among different tissues and also among different cells within the same tissues. Coreceptor-positive cells are more frequently identified in the colon than in the rectum and more frequently identified in the cervix than in the vagina, suggesting that the expression levels of coreceptors are differentially regulated at different anatomic sites. Furthermore, extremely high levels of CXCR4 and CCR3 expression are found on the neurons from both the central and peripheral nervous systems. These findings may be helpful in understanding certain aspects of HIV and SIV pathogenesis and transmission.

Animals↗