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Biomedical subjects

Q Yu

Publications and source records attributed to Q Yu.

At least 109 records · Page 6Linked to original sources

Central skull base invasion of maxillofacial tumors: computed tomography appearance.

OBJECTIVE: The aim of this study was to demonstrate computed tomography (CT) features of maxillofacial tumors invading the central skull base and to offer information in aiding diagnosis. METHODS: Fifty-eight maxillofacial tumors with central skull base invasion shown on axial and coronal CT images were divided into benign (13 cases) and malignant (45 cases) groups, based on their pathologic outcomes as proven by biopsy and surgery. RESULTS: Four manifestations of the skull base abnormality were observed on CT images: (1) resorption of central skull base (53 cases, 11 benign and 42 malignant tumors); (2) enlargement of the foramen and canal in the central skull base (20 cases, 4 benign and 16 malignant tumors); (3) thinning of the central skull base (11 cases, 8 benign and 3 malignant tumors); and (4) displacement of the central skull base (5 cases, all benign tumors). The following structures of the central skull base were involved: the roof of the pterygoid process of the sphenoid bone (49 cases), the sphenoid greater wing (37 cases), the sphenoid body and sinus (33 cases), the petrous apex (12 cases), the clivus (4 cases), and the articular surface of the temporal squama (3 cases). Of 58 patients, 30 (7 benign and 23 malignant) had tumors with central skull base erosion that infiltrated into the cranial cavity. CONCLUSION: Benign maxillofacial tumors with center skull base erosion tended to lead to the displacement and thinning of the base of the middle skull fossa in contrast with tumors with malignant maxillofacial tumors. It is believed that these CT manifestations might be valuable in making a differential diagnosis.

Adolescent↗

The bulk of the phosphorylation of human respiratory syncytial virus phosphoprotein is not essential but modulates viral RNA transcription and replication.

The ability of variants of the human respiratory syncytial virus (HRSV) phosphoprotein (P protein) to support RNA transcription and replication has been studied by using HRSV-based subgenomic replicons. The serine residues normally phosphorylated in P during HRSV infection have been replaced by other residues. The results indicate that the bulk of phosphorylation of P (98%) is not essential for viral RNA transcription or replication but that phosphorylation can modulate these processes.

HN Protein↗

Isolation of Orientia tsutsugamushi from Leptotrombidium fuji and its characterization.

In our attempts to isolate Orientia tsutsugamushi from trombiculid mites, a strain was successfully isolated from Leptotrombidium fuji collected in Aichi Prefecture, Japan. This is the first case of isolation of O. tsutsugamushi from L. fuji. A phylogenetic analysis based on the base-sequence homology of the 56-kDa type-specific antigen-gene indicated that the strain is a new type which is not closely related to any strains analyzed previously. Three strains isolated from Leptotrombidium pallidum harvested at the same area were identified as being closely related to the JP-2 type (subtype-2 of Karp type in Japan) by phylogenetic analysis.

Animals↗

Gene transfer of the neuronal NO synthase isoform to cirrhotic rat liver ameliorates portal hypertension.

Reduced production of nitric oxide (NO) in the cirrhotic liver results from a defect in hepatic endothelial cell nitric oxide synthase (ecNOS) and appears to contribute to the high intrahepatic resistance and portal hypertension typical of cirrhosis. Therefore, we postulated that targeting a heterologous NOS isoform to sinusoidal endothelial cells or other perisinusoidal cells, such as hepatic stellate cells, would counter the defect in NO production and reduce resistance to blood flow. Recombinant adenovirus (Ad) carrying the neuronal NOS gene (nNOS) targeted liver sinusoidal endothelial cells, stellate cells, and hepatocytes more efficiently than the corresponding cells in cirrhotic livers, but transduction rates were substantial even in cirrhotic animals. Expression of nNOS in each liver cell type, whether from normal or injured liver, caused increased NO production and inhibited endothelin-1-induced contractility of perisinusoidal stellate cells. Finally, in 2 different in vivo models of cirrhosis and portal hypertension, transduction of livers with recombinant Ad.nNOS significantly reduced intrahepatic resistance and portal pressure. The data highlight the feasibility of gene transfer to diseased liver and hepatic cells and demonstrate the potential of a novel therapy for portal hypertension caused by cirrhosis.

Adenoviridae↗

[Clinical manifestation and pathological change of autoimmune hepatitis].

OBJECTIVE: To determine clinical manifestation and pathological changes in autoimmune hepatitis (AIH) by liver biopsy. METHODS: The clinical manifestation and pathological changes by liver biopsy in 14 AIH patients were investigated retrospectively. RESULTS: Clinically, AIH affects females with a females/male ratio of 13/1, the age range was 28-66 year; there was extended elevation of ALT and AST, hyperglobulinemia, hypergammaglobulinemia with predominant elevation of IgG and different kinds of antibodies. Patients usually had autoimmune diseases with pathological change of typical chronic hepatitis. The levels of globulin (33 approximately 60 g/L), gammaglobulin (23.9% approximately 60.5%), IgG (8.2 approximately 39. 0 g/L), ds-DNA (1.5 approximately 58.0 g/L) in AIH were significantly higher than those of normal (t=9.7, 9.3, 6.2, 3.5, P<0.01). CONCLUSION: AIH has severe liver impairment with many other symptoms due to multi-systemic damage out of liver. AIH is a distinct autoimmune disease.

Adult↗

New types of X-ray computed tomography (CT) with synchrotron radiation: fluorescent X-ray CT and phase-contrast X-ray CT using interferometer.

New types of X-ray computed tomography (CT), fluorescent X-ray CT and phase-contrast X-ray CT are being developed for biomedical research. While fluorescent scanning X-ray CT (FXCT) can detect specific contrast elements, or endogenous iodine, at very low content (less than 400 pg iodine of tissue in a volume of 8 x 10(-6) ml), the phase-contrast X-ray CT (PCCT) is a highly sensitive imaging technique to differentiate between different biological tissue types (based on their specific gravity variation) without the use of a contrast agent. Therefore, we can expect functional diagnosis with FXCT, and high contrast, high resolution biological imaging with PCCT. In this paper, a human thyroid gland imaged by FXCT, and a metastatic human cancerous lesion depicted using PCCT are presented. The latter method used a newly manufactured, large, monolithic, X-ray interferometer, which is described in this paper in detail.

Colonic Neoplasms↗

Screening for mt-DNA mutations in optic neuritis of unknown cause.

OBJECTIVE: To investigate mitochondrial DNA (mt-DNA) mutations in optic neuritis of unknown cause (ONUC) and to assess the practical value of mt-DNA mutation detection in etiologically and differentially diagnosing ONUC. METHODS: Thirty patients with ONUC were screened for mt-DNA mutations of nt11778, nt3460 and nt15257 by using SSCP, mutation-specific primer PCR and sequencing. RESULTS: mt-DNA mutations were found in twelve of thirty ONUC patients. All of the mutations were at nt11778 position, but no one at nt3460 and nt15257. CONCLUSIONS: Forty percent (12/30) of ONUC patients were caused by an mt-DNA mutation. Combined with other routine measures, screening for mt-DNA mutations in ONUC patients is of great significance in diagnosing ONUC etiologically and differentially.

Adolescent↗

[The study on effects of human fetal liver cells on immunity of BALB/c mice].

This study sought to better understand the effects of human fetal liver cells(FLC) on immunity. FLC were injected into BALB/c mice intraperitoneally. The design included four groups: negative control and three dose (125 x 10(5), 25 x 10(5), 5 x 10(5) FLC/day) groups. The results showed that FLC increased the thymus visceral coefficient, numbers of T-lymphocytes(TLC) and lymphocytes(LC) in blood, total number of spleen cells, the number of plaque forming cells(PFC) of spleen, the rate(%) of transformation and stimulus index of TLC of spleen, and the function of macrophages. FLC also effected the function of natural killer cells(NK cells) of BALB/c mice. The findings suggest that human FLC can strengthen the nonspecific immunity, humoral immunity and cellular immunity in mice. In this study, however, no effect of FLC on spleen visceral coefficient was noticed, and no sign of delayed type allergy was observed.

Animals↗

[Mutation analysis of the tumor suppressor gene PTEN/MMAC1/TEP1 in human hepatocellular carcinoma].

PTEN/MMAC1/TEP1 is a tumor suppressor gene. Its mutation has been found in several different types of human cancers. 34 primary human hepatocellular carcinomas have been examined for mutations in exon 5 and exon 8 of the PTEN gene. Exon 5 and exon 8 were amplified by polymerase chain reaction (PCR) with intronic primers and subjected to single strand conformation polymorphism (SSCP) analysis. SSCPs were found in 4 of the 34 hepatocellular carcinomas analyzed. Direct sequencing of the PCR products identified single base-pair substitutions in the four tumor DNA samples, two in intron 4 and two in exon 8. One of the base-pair substitution in exon 8 is a missense mutation, which changed codon 304 of PTEN protein from Cys to Gly. These data suggest that PTEN may be involved in the carcinogenesis and development of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

[CT manifestation of pterygopalatine fossa in adult skull].

OBJECTIVE: The aim of this study was to measure certain diameters of the pterygopalatine fossa (PPF) and to discuss the anatomic appearance of PPF on CT images. METHODS: 20 dry skulls were scanned by CT on axial and coronal plane with 2 mm slice thickness. RESULTS: On CT imaging, the shape of superior 1/4 part of PPF is mainly shown as biconcavity. The maximal posteroanterial (PA)diameter was (6.6+/-2.2)mm. The maximal medialateral diameter (ML)was (13.7+/-3.7)mm. The shape of the middle 1/4 part of PPF was biconvexity with the PA and ML of (6.6+/-2.1)mm and (12.1+/-2.7)mm. The shape of the inferior 1/2 part of PPF just liked a tube with the diameter of (3.8+/-1.7)mm. The foramen rotudum lied (5.2+/-2.3)mm under the inferior orbital fissure. The pterygoid canal lied (7.4+/-2.5)mm medial and (6.2.+/-4.2)mm inferior to the foramen rotudum. CONCLUSION: PPF has various shapes on axial and coronal CT images. Based on the distances and the relationship between the foramen and fissures, the normal and abnormal status of PPF can be evaluated.

English Abstract↗

Two Different Accretion Classes in Seyfert 1 Galaxies and QSOs.

The mass of the central black holes in Seyfert galaxies and QSOs can be determined from the broad emission lines and the reverberation method. Using the measured black hole mass and the bolometric or ionizing luminosity, the accretion rate can be estimated. Compiling a sample of Seyfert 1 galaxies and QSOs with reliable central masses, estimated ionizing luminosities, and X-ray spectral slopes, we find that the X-ray spectral slope strongly correlates with the accretion rate. The objects in the sample are found to be distributed in two distinct classes in the spectral index versus log&parl0;Lion&solm0;LEdd&parr0;-plane. We argue that these two classes may correspond to advection-dominated accretion flow (ADAF) and thin disk accretion. The observations of a "two-state" Seyfert 1 galaxy, 1H 0419-577, confirm our results. Detailed fitting of the spectra of individual Seyfert 1 galaxies and QSOs using ADAF and/or thin disk models should further clarify the two-class classification.

Journal Article↗

Identification of an oxygen responsive enhancer element in the glyceraldehyde-3-phosphate dehydrogenase gene.

The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is induced by hypoxia in endothelial cells (EC). Upregulation occurs primarily at the level of transcription and occurs to a much greater extent in EC than in other cell types. To characterize EC specific hypoxia response elements within the GAPDH gene, we performed transient transfection studies in EC, fibroblasts and smooth muscle cells using portions of the GAPDH promoter linked to a CAT reporter gene. These initial studies identified an EC specific hypoxia responsive region that was further characterized (using SV40-promoter-CAT reporter constructs) as a 19-nucleotide sequence (-130 to -112) containing both an hypoxia inducible factor-1 (HIF-1)-binding site and a novel flanking sequence. Electrophoretic mobility shift assays confirmed inducible EC protein binding to this fragment. Mutation of either the HIF-1-binding site or the flanking sequence resulted in complete loss of function and loss of inducible protein binding. Thus, a single HIF-1-binding site is necessary, but not sufficient, for hypoxic regulation of GAPDH in EC. Furthermore, the novel HIF-1 flanking sequence required for GAPDH upregulation and the protein(s) that bind to it may be EC specific.

Animals↗

Induction of antitumor immunity with dendritic cells transduced with adenovirus vector-encoding endogenous tumor-associated antigens.

Dendritic cells (DCs) are professional Ag-presenting cells that are being considered as potential immunotherapeutic agents to promote host immune responses against tumor Ags. In this study, recombinant adenovirus (Ad) vectors encoding melanoma-associated Ags were used to transduce murine DCs, which were then tested for their ability to activate CTL and induce protective immunity against B16 melanoma tumor cells. Immunization of C57BL/6 mice with DCs transduced with Ad vector encoding the hugp100 melanoma Ag (Ad2/hugp100) elicited the development of gp100-specific CTLs capable of lysing syngeneic fibroblasts transduced with Ad2/hugp100, as well as B16 cells expressing endogenous murine gp100. The induction of gp100-specific CTLs was associated with long term protection against lethal s.c. challenge with B16 cells. It was also possible to induce effective immunity against a murine melanoma self Ag, tyrosinase-related protein-2, using DCs transduced with Ad vector encoding the Ag. The level of antitumor protection achieved was dependent on the dose of DCs and required CD4+ T cell activity. Importantly, immunization with Ad vector-transduced DCs was not impaired in mice that had been preimmunized against Ad to mimic the immune status of the general human population. Finally, DC-based immunization also afforded partial protection against established B16 tumor cells, and the inhibition of tumor growth was improved by simultaneous immunization against two melanoma-associated Ags as opposed to either one alone. Taken together, these results support the concept of cancer immunotherapy using DCs transduced with Ad vectors encoding tumor-associated Ags.

Adenoviridae↗

Identification of a defect in the intracellular trafficking of a Kell blood group variant.

Blood group polymorphisms have been used as tools to study the architecture of the red blood cell (RBC) membrane. Some blood group variants have reduced antigen expression at the cell surface. Understanding the underlying mechanism for this reduced expression can potentially provide structural information and help to elucidate protein trafficking pathways of membrane proteins. The Kp(a+) phenotype is a variant in the Kell blood group system that is associated with a single amino acid substitution (R281W) in the Kell glycoprotein and serologically associated with a weakened expression of other Kell system antigens by an unknown mechanism. We found by immunoblotting of RBCs that the weakening of Kell antigens in this variant is due to a reduced amount of total Kell glycoprotein at the cell surface rather than to the inaccessibility of the antigens to Kell antibodies. Using a heterologous expression system, we demonstrate that the Kpa mutation causes retention of most of the Kell glycoprotein in a pre-Golgi compartment due to differential processing, thereby suggesting aberrant transport of the Kell protein to the cell surface. Furthermore, we demonstrated that single nucleotide substitutions into the coding region of the common KEL allele, as predicted by the molecular genotyping studies, was sufficient to encode three clinically significant low incidence antigens. We found that two low incidence antigens can be expressed on a single Kell protein, thus showing that the historical failure to detect such a variant is not due to structural constraints in the Kell protein. These studies demonstrate the power of studying the molecular mechanisms of blood group variants for elucidating the intracellular transport pathways of membrane proteins and the requirements for cell surface expression.

Alleles↗

Synthesis of novel phenserine-based-selective inhibitors of butyrylcholinesterase for Alzheimer's disease.

Four novel analogues (8-11) of cymserine (2) were synthesized by methods similar to those recently developed for the total syntheses of N8-norphenserine (Yu, Q. S.; et al. J. Med. Chem. 1997, 40, 2895-2901) and N1,N8-bisnorphenserine (Yu, Q. S.; et al. J. Med. Chem. 1998, 41, 2371-2379). As our structure-activity studies predicted, these compounds are highly potent and selective inhibitors of human butyrylcholinesterase (BChE) and will test the novel hypothesis that BChE inhibitors are useful in the treatment of Alzheimer's disease. In a similar manner, the same modifications that provided BChE selectivity were applied to the acetylcholinesterase (AChE)-selective inhibitor, tolserine (5), to provide the novel tolserine analogues 12-15. As predicted, these modifications altered the AChE-selective action of tolserine (5) to favor a lack of cholinesterase enzyme subtype selectivity.

Acetylcholinesterase↗

Complementarity between 3' terminal nucleotides of tRNA and primer binding site is a major determinant for selection of the tRNA primer used for initiation of HIV-1 reverse transcription.

The initiation of reverse transcription of human immunodeficiency virus type 1 (HIV-1) exclusively utilizes tRNALys,3 as a primer. Previous studies have shown that HIV-1 could use alternative tRNAs, such as tRNAIle or tRNAHis, to initiate reverse transcription only if the primer binding site (PBS) was made complementary to the 3' terminal 18 nucleotides of the cognate tRNA. However, upon in vitro culture, the viruses with a PBS complementary to the alternative tRNAs rapidly reverted to generate a PBS complementary to tRNALys,3. To investigate the process of reversion, we have constructed defective proviral genomes that contain a PBS complementary to tRNAIle or tRNAHis. The genomes contain the gene for xanthine-guanosine phosphoribosyl transferase (gpt) in place of env. Cotransfection of these proviral genomes with a plasmid-encoding vesicular stomatitis virus G protein (VSV-G) results in viruses that undergo a single round of HIV-1 infection; successful infections are scored as cells resistant to the drug mycophenolic acid. Using this single-round infection system, we demonstrated that HIV-1 with a PBS complementary to tRNAIle or tRNAHis is three- to fivefold less efficient in replication as measured by production of drug-resistant cell colonies compared to the wild-type virus. These viruses predominantly used the cognate tRNA as primer in their initial round of replication, although we did obtain a single cell colony in which the PBS was complementary to tRNALys,3. Using an HIV-1 provirus with a PBS complementary to yeast tRNAPhe, we established a single-round infection system in which the infectivity of this mutant HIV-1 relies on transfected yeast tRNAPhe. The results of our studies suggest that the mechanism for selection of the tRNA primer for initiation of reverse transcription relies primarily on the complementarity between the tRNA primerthe PBS.

Binding Sites↗