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Biomedical subjects

M T Liu

Publications and source records attributed to M T Liu.

At least 19 recordsLinked to original sources
PubMed2006

Cytokine gene polymorphisms in bullous pemphigoid in a Chinese population.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune bullous disease mostly associated with autoantibodies to the hemidesmosomal BP autoantigens BP180 and BP230. High levels of interleukin (IL)-1beta, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma have been detected in skin lesions or sera of patients with BP. Cytokine gene polymorphisms may affect cytokine production and contribute to susceptibility to autoimmune diseases. Until now, no cytokine gene polymorphism study has been conducted on patients with BP. OBJECTIVES: We aimed to determine whether the genetic polymorphisms of the cytokine genes might influence the development of BP. METHODS: DNA samples were obtained from 96 BP patients and 174 control subjects. Using direct sequencing and microsatellite genotyping, we examined 23 polymorphisms in 11 cytokine genes including the IL-1alpha, IL-1beta, IL-1 receptor antagonist, IL-4, IL-6, IL-8, IL-10, IL-13, IL-4 receptor, TNF-alpha and IFN-gamma genes. RESULTS: Although the BP patients were more likely to carry the -511T and -31C alleles of the IL-1beta gene (P = 0.04), the significance disappeared after correction for multiple testing (Pc). There was complete linkage disequilibrium between the -511T and -31C alleles of the IL-1beta gene. In female patients with BP, the associations with IL-1beta (-511T) and (-31C) alleles were much stronger (68% vs. 40.6%, odds ratio = 3.11, Pc = 0.006). No significantly different allelic and genotypic distributions of other cytokine gene polymorphisms could be found between the patients with BP and controls. Moreover, no association with the extent of disease involvement (localized or generalized) was observed. CONCLUSIONS: The IL-1beta (-511) and (-31) polymorphisms were significantly associated with BP in women. The other genetic polymorphisms of cytokine genes that we analysed do not appear to be associated with BP susceptibility in our Chinese population.

Adult↗
PubMed2003

Decommissioning of a 60Co unit and estimation of personal doses.

Chang-hua Christian Hospital needs to uninstall the 60Co unit. The mode of this 60Co teletherapy unit is SHIMADZU RTGS-10. The original lead head was taken as the source container of this 60Co unit. The source head was dismantled and put into the prepared wooden box, after the source was sealed. This study describes the planning and dismantling of the retirement and transport of the 60Co unit, and personal doses measured during the procedure. This work estimates the doses of radiation received by exposed workers during the dismantling of the machine. The workers received doses of approximately 53 microSv. This study shows that the original lead head can be used as the source container of this 60Co unit. The 60Co machine was smoothly dismantled and transported by conscientious and careful workers, using planned and controlled radiation protection, following the ALARA (as low as reasonably achievable) rule.

Body Burden↗
PubMed2001

Neutralization of the chemokine CXCL10 reduces inflammatory cell invasion and demyelination and improves neurological function in a viral model of multiple sclerosis.

Intracerebral infection of mice with mouse hepatitis virus (MHV) results in an acute encephalomyelitis followed by a chronic demyelinating disease with clinical and histological similarities with the human demyelinating disease multiple sclerosis (MS). Following MHV infection, chemokines including CXC chemokine ligand (CXCL)10 (IFN inducible protein 10 kDa), CXCL9 (monokine induced by IFN-gamma), and CC chemokine ligand 5 (RANTES) are expressed during both acute and chronic stages of disease suggesting a role for these molecules in disease exacerbation. Previous studies have shown that during the acute phase of infection, T lymphocytes are recruited into the CNS by the chemokines CXCL10 and CXCL9. In the present study, MHV-infected mice with established demyelination were treated with antisera against these two chemokines, and disease severity was assessed. Treatment with anti-CXCL10 reduced CD4+ T lymphocyte and macrophage invasion, diminished expression of IFN-gamma and CC chemokine ligand 5, inhibited progression of demyelination, and increased remyelination. Anti-CXCL10 treatment also resulted in an impediment of clinical disease progression that was characterized by a dramatic improvement in neurological function. Treatment with antisera against CXCL9 was without effect, demonstrating a critical role for CXCL10 in inflammatory demyelination in this model. These findings document a novel therapeutic strategy using Ab-mediated neutralization of a key chemokine as a possible treatment for chronic human inflammatory demyelinating diseases such as MS.

Animals↗
PubMed2001

Reduced macrophage infiltration and demyelination in mice lacking the chemokine receptor CCR5 following infection with a neurotropic coronavirus.

Studies were performed to investigate the contributions of the CC chemokine receptor CCR5 in host defense and disease development following intracranial infection with mouse hepatitis virus (MHV). T cell recruitment was impaired in MHV-infected CCR5(-/-) mice at day 7 postinfection (pi), which correlated with increased (P < or = 0.03) titers within the brain. However, by day 12 pi, T cell infiltration into the CNS of infected CCR5(-/-) and CCR5(+/+) mice was similar and both strains exhibited comparable viral titers, indicating that CCR5 expression is not essential for host defense. Following MHV infection of CCR5(+/+) mice, greater than 50% of cells expressing CCR5 antigen were activated macrophage/microglia (determined by F4/80 antigen expression). In addition, infected CCR5(-/-) mice exhibited reduced (P < or = 0.02) macrophage (CD45(high)F4/80(+)) infiltration, which correlated with a significant reduction (P < or = 0.001) in the severity of demyelination compared to CCR5(+/+) mice. These data indicate that CCR5 contributes to MHV-induced demyelination by allowing macrophages to traffic into the CNS.

Animals↗
PubMed2001

Expression of Mig (monokine induced by interferon-gamma) is important in T lymphocyte recruitment and host defense following viral infection of the central nervous system.

Induction of a Th1 immune response against viral infection of the CNS is important in contributing to viral clearance. The present studies demonstrate a role for the T cell chemoattractant chemokine Mig (monokine induced by IFN-gamma) in contributing to a Th1 response against mouse hepatitis virus infection of the CNS. Analysis of the kinetics of Mig expression revealed mRNA transcripts present at days 7 and 12 postinfection (p.i.) but not early (day 2) or late (day 35) in the infection. To determine functional significance, mouse hepatitis virus-infected mice were treated with anti-Mig antisera, and the severity of disease was evaluated. Such treatment resulted in a marked increase in mortality that correlated with a >3 log increase in viral burden within the brains as compared with control mice treated with normal rabbit serum. Anti-Mig-treated mice displayed a significant decrease (p < 0.005) in CD4(+) and CD8(+) T cell recruitment into the CNS as compared with normal rabbit serum-treated mice. In addition, anti-Mig treatment resulted in a significant decrease (p < 0.05) in levels of IFN-gamma and IFN-beta that coincided with increased (p < 0.02) expression of the anti-inflammatory Th2 cytokine IL-10 within the CNS. Collectively, these data indicate that Mig is important in contributing to host defense by promoting a protective Th1 response against viral infection of the CNS.

Amino Acid Sequence↗
PubMed2001

Pituitary adenylate cyclase activating peptide (PACAP) in the enteropancreatic innervation.

Pancreatic ganglia are innervated by neurons in the gut and are formed by precursor cells that migrate into the pancreas from the bowel. The innervation of the pancreas, therefore, may be considered an extension of the enteric nervous system. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present in a subset of enteric neurons. We investigated the presence of PACAP in the enteropancreatic innervation in guinea pigs, and the response of pancreatic neurons to PACAP-related peptides. PACAP immunoreactivity was found in nerve fibers in both enteric and pancreatic ganglia and in nerve bundles that travelled between the duodenum and pancreas. PACAP-immunoreactive nerve fibers were densely distributed in the pancreatic ganglia, where they surrounded a subset of cholinergic cell bodies. Pancreatic ganglia did not contain PACAP-immunoreactive cell bodies; however, neuronal perikarya with PACAP immunoreactivity were found in the myenteric plexus of the duodenum. These cells co-stored vasoactive intestinal peptide (VIP). PACAP depolarized pancreatic neurons. Pancreatic neurons were also depolarized by VIP; however, PACAP was more efficacious at depolarizing pancreatic cells than VIP. These findings are consistent with the view that the PACAP effects were mediated through PACAP-selective (PAC1) receptors. PACAP-responsive neurons displayed PAC1 receptor immunoreactivity, which was also found in islet cells and enteric neurons. These results provide support for the hypothesis that PACAP modulates reflex activity between the gut and pancreas. The excitatory effect of PACAP would be expected to potentiate pancreatic secretion.

Animals↗
PubMed2001

Skin dose measurement by using ultra-thin TLDs.

The treatment schedule for radiation therapy is often interrupted because of complicated skin reactions. Quantitative information relating beam parameters and skin reactions will be helpful. Measurements were performed for 6-15 MV photons and 6-21 MeV electrons with ultra thin TLD films (GR-200F, surface area 0.5 x 0.5cm2, nominal thickness 5 mg cm(-2)). The skin doses for various field sizes, ranging from 10 x 10 to 40 x 40 cm2, and various incident angles of beam from 0 degrees to 80 degrees were measured. The ratios of skin dose to maximum dose in phantom for 10 x 10 cm2 are 16.10+/-0.68%, 14.03+/-1.04% and 10.59+/-0.64% for 6, 10 and 15 MV, respectively. Such ratios increase with a larger field size. For electrons the ratios are 72.59+/-1.72%, 78.52+/-2.99%, 78.89+/-2.86%, 86.08+/-2.62%. 87.75+/-1.94% and 86.33+/-3.09% for 6, 9, 12, 15, 18 and 21 MeV, respectively. They also increase with a larger size. The oblique factors also increase with larger incident angle.

Electrons↗
PubMed2001

The measurement of photoneutrons in the vicinity of a Siemens Primus linear accelerator.

This study involves the measurement of photoneutron contamination emitted from a Siemens Primus medical linear accelerator by using BD-PND bubble detectors. Various bubble detectors were arranged around the linac head with the interval of I m and at the same height as the isocenter to measure the dose equivalent distribution in the treatment room. The measurements were performed for 15 MV X-rays with 40 x 40cm2 and 0 x 0cm2 fields and for 15,18, and 21 MeV electrons with 25 x 25 cm2 electron cone. Neutron dose equivalent rate at the points of measurement in the treatment room decreased with increasing distance to the isocenter. The maximum neutron dose equivalents were at the isocenter, and the values for 15MV 40 x 40 and 0 x 0 cm2 were 1843+/-90 and 169.9+/-59.9 microSv per Gy X-ray, respectively. The values for 15, 18 and 21 MeV electrons with 25 x 25 cm2 cones were 100.0+/-20.4, 262.7+/-61.2 and 349.0+/-29.6 microSv per Gy electron, respectively. The neutron contamination of electrons less than 12 MeV was below the detection limit.

Journal Article↗
PubMed2001

Dose compensation of the total body irradiation therapy.

The aim of the study is to improve dose uniformity in the body by the compensator-rice and to decrease the dose to the lung by the partial lung block. Rando phantom supine was set up to treat bilateral fields with a 15 MV linear accelerator at 415cm treatment distance. The experimental procedure included three parts. The first part was the bilateral irradiation without rice compensator, and the second part was with rice compensator. In the third part, rice compensator and partial lung block were both used. The results of thermoluminescent dosimeters measurements indicated that without rice compensator the dose was non-uniform. Contrarily, the average dose homogeneity with rice compensator was measured within +/- 5%, except for the thorax region. Partial lung block can reduce the dose which the lung received. This is a simple method to improve the dose homogeneity and to reduce the lung dose received. The compensator-rice is cheap, and acrylic boxes are easy to obtain. Therefore, this technique is suitable for more studies.

Humans↗
PubMed2001

Chemokine expression and viral infection of the central nervous system: regulation of host defense and neuropathology.

An effective host response against viral infection of the central nervous system (CNS) is the principal factor dictating the outcome of infection. It is the responsibility of the immune response to contain and control viral replication. Paradoxically, it is the immune response that may also contribute to the development of neuropathology. We have used mouse hepatitis virus (MHV), apositive-strand RNA virus, infection of the CNS to understand the dynamic interaction between viral replication, protection, and pathology with an emphasis on understanding how chemokines participate in these interrelated processes. Herein, we demonstrate the complexity of the chemokine response to MHV infection of the CNS and the delicate balance that exists between host defense and development of disease.

Animals↗
PubMed2001

Primary tumour volume delineation in nasopharyngeal carcinoma and correlation with 1997 AJCC tumour stage classification.

OBJECTIVE: To investigate the variability in primary tumour volume in nasopharyngeal carcinoma and compare it with the tumour staging of the 1997 American Joint Committee on Cancer. DESIGN: Prospective study. SETTING: Tertiary care centre. METHOD: A series of 33 newly diagnosed patients who were treated with high-dose radiotherapy participated in the study. MAIN OUTCOME MEASURES: Using computed tomographic scans, primary tumour volumes were measured using the summation-of-areas technique, and the variability in tumour volume was determined. The Mann-Whitney test was used for statistical analysis. RESULTS: A large variation in primary tumour volume was observed, especially in advanced-stage cases. CONCLUSIONS: Nasopharyngeal carcinoma shows considerable variability in primary tumour volume. Incorporation of primary tumour volume may lead to further refinement of the 1997 tumour staging system.

Adult↗
PubMed2000

Induction of cytokine genes and IL-1alpha by chemical hypoxia in PC12 cells.

The role of cytokine in neuronal injury was examined in rat pheochromocytoma (PC12) cells under chemical hypoxia (i.e. KCN) and glucose deprivation. The mRNA levels of interleukin-1alpha (IL-1alpha), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured by reverse transcription-polymerase chain reaction (RT-PCR) in PC12 cells exposed to 0.5 mM KCN for various time intervals. Cytokine mRNA levels expressed to peak levels 30 minutes after KCN treatment and declined gradually until 240 min. The IL-1alpha activity reached the highest levels 2 hr after the same KCN treatment. Under parallel conditions, KCN increased cytosolic free calcium concentration ([Ca2+]i) in the absence of glucose. However, IL-1alpha mRNA induction by KCN was not altered under calcium-free conditions in PC12 cells, indicating its induction was Ca2+-independent. However, the phosphatidylcholine (PC)-specific phospholipase C (PLC) inhibitor D609 decreased the KCN-induced IL-1alpha mRNA and protein in PC12 cells suggests that PC-PLC might play a role in cytokine induction during hypoxia.

Animals↗
PubMed2000

The T cell chemoattractant IFN-inducible protein 10 is essential in host defense against viral-induced neurologic disease.

The contribution of the T cell chemoattractant chemokine IFN-inducible protein 10 (IP-10) in host defense following viral infection of the CNS was examined. IP-10 is expressed by astrocytes during acute encephalomyelitis in mouse hepatitis virus-infected mice, and the majority of T lymphocytes infiltrating into the CNS expressed the IP-10 receptor CXCR3. Treatment of mice with anti-IP-10 antisera led to increased mortality and delayed viral clearance from the CNS as compared with control mice. Further, administration of anti-IP-10 led to a >70% reduction (p </= 0.001) in CD4+ and CD8+ T lymphocyte infiltration into the CNS, which correlated with decreased (p </= 0.01) levels of IFN-gamma. These data indicate that IP-10 functions as a sentinel molecule in host defense and is essential in the development of a protective Th1 response against viral infection of the CNS.

Acute Disease↗
PubMed2000

Insights into molybdenum cofactor deficiency provided by the crystal structure of the molybdenum cofactor biosynthesis protein MoaC.

BACKGROUND: The molybdenum cofactor (Moco) is an essential component of a large family of enzymes involved in important transformations in carbon, nitrogen and sulfur metabolism. The Moco biosynthetic pathway is evolutionarily conserved and found in archaea, eubacteria and eukaryotes. In humans, genetic deficiencies of enzymes involved in this pathway trigger an autosomal recessive and usually deadly disease with severe neurological symptoms. The MoaC protein, together with the MoaA protein, is involved in the first step of Moco biosynthesis. RESULTS: MoaC from Escherichia coli has been expressed and purified to homogeneity and its crystal structure determined at 2 A resolution. The enzyme is organized into a tightly packed hexamer with 32 symmetry. The monomer consists of an antiparallel, four-stranded beta sheet packed against two long alpha helices, and its fold belongs to the ferredoxin-like family. Analysis of structural and biochemical data strongly suggests that the active site is located at the interface of two monomers in a pocket that contains several strictly conserved residues. CONCLUSIONS: Asp128 in the putative active site appears to be important for catalysis as its replacement with alanine almost completely abolishes protein activity. The structure of the Asp128-->Ala variant reveals substantial conformational changes in an adjacent loop. In the human MoaC ortholog, substitution of Thr182 with proline causes Moco deficiency, and the corresponding substitution in MoaC severely compromises activity. This residue is located near the N-terminal end of helix alpha4 at an interface between two monomers. The MoaC structure provides a framework for the analysis of additional dysfunctional mutations in the corresponding human gene.

Amino Acid Sequence↗
PubMed2000

Crystal structure of the gephyrin-related molybdenum cofactor biosynthesis protein MogA from Escherichia coli.

Molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway in archaea, eubacteria, and eukaryotes, including humans. Genetic deficiencies of enzymes involved in this biosynthetic pathway trigger an autosomal recessive disease with severe neurological symptoms, which usually leads to death in early childhood. The MogA protein exhibits affinity for molybdopterin, the organic component of Moco, and has been proposed to act as a molybdochelatase incorporating molybdenum into Moco. MogA is related to the protein gephyrin, which, in addition to its role in Moco biosynthesis, is also responsible for anchoring glycinergic receptors to the cytoskeleton at inhibitory synapses. The high resolution crystal structure of the Escherichia coli MogA protein has been determined, and it reveals a trimeric arrangement in which each monomer contains a central, mostly parallel beta-sheet surrounded by alpha-helices on either side. Based on structural and biochemical data, a putative active site was identified, including two residues that are essential for the catalytic mechanism.

Amino Acid Sequence↗
PubMed2000

A central role for CD4(+) T cells and RANTES in virus-induced central nervous system inflammation and demyelination.

Infection of C57BL/6 mice with mouse hepatitis virus (MHV) results in a demyelinating encephalomyelitis characterized by mononuclear cell infiltration and white matter destruction similar to the pathology of the human demyelinating disease multiple sclerosis. The contributions of CD4(+) and CD8(+) T cells in the pathogenesis of the disease were investigated. Significantly less severe inflammation and demyelination were observed in CD4(-/-) mice than in CD8(-/-) and C57BL/6 mice (P < or = 0.002 and P < or = 0.001, respectively). Immunophenotyping of central nervous system (CNS) infiltrates revealed that CD4(-/-) mice had a significant reduction in numbers of activated macrophages/microglial cells in the brain compared to the numbers in CD8(-/-) and C57BL/6 mice, indicating a role for these cells in myelin destruction. Furthermore, CD4(-/-) mice displayed lower levels of RANTES (a C-C chemokine) mRNA transcripts and protein, suggesting a role for this molecule in the pathogenesis of MHV-induced neurologic disease. Administration of RANTES antisera to MHV-infected C57BL/6 mice resulted in a significant reduction in macrophage infiltration and demyelination (P < or = 0.001) compared to those in control mice. These data indicate that CD4(+) T cells have a pivotal role in accelerating CNS inflammation and demyelination within infected mice, possibly by regulating RANTES expression, which in turn coordinates the trafficking of macrophages into the CNS, leading to myelin destruction.

Animals↗
PubMed2000

Effects of radiotherapy for nasopharyngeal carcinoma on the paranasal sinuses: study based on computed tomography scanning.

OBJECTIVE: The purpose of this study was to determine if radiotherapy for nasopharyngeal carcinoma causes mucosal disease of the paranasal sinuses. DESIGN: This study was a retrospective study. SETTING: This study was conducted at a tertiary care centre. METHOD: A series of 69 newly diagnosed patients, without pre-existing sinus disease, who were treated with high-dose radiotherapy participated. MAIN OUTCOME MEASURES: The prevalence, severity, and time course of mucosal abnormalities were analyzed, as judged by consecutive computed tomographies (CTs). RESULTS: The CT study revealed that 58.8% of the postirradiation scans had mucosal disease of the sinuses. The maxillary sinus had the highest prevalence (42.3%) without statistical significance (p = .10). The difference by McNemar test for two follow-up scans was not significant (p = .48) and by Kappa test was significant (p = .04). The relationship between the prevalence and the time course post radiotherapy revealed that it remained a high prevalence until after the 4-year follow-up scans. CONCLUSIONS: The results of this study confirm that chronic sinus disease is a common late complication of radiotherapy and it persists for years. Thus, aggressive treatment is indicated.

Adolescent↗