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Y Guo

Publications and source records attributed to Y Guo.

At least 181 records · Page 10Linked to original sources
PubMed2000

Abnormal illness behavior and psychiatric disorders: a study in an outpatient clinic in Japan.

Abnormal illness behavior, such as hypochondriacal attitude and inappropriate treatment-seeking, has been associated with various psychiatric disorders in which patients tend to abuse medical services and seek inappropriate treatment in general practice clinics rather than psychiatric clinics. However, the relationship between illness behavior and psychiatric disorders in Japan is yet to be elucidated. We examined the abnormal illness behavior of 243 patients who visited the outpatient department of psychiatry at Saga Medical School Hospital, Saga, Japan, using a Japanese version of the Illness Behavior Questionnaire (IBQ). Multivariate analysis indicated significant association between some of the IBQ scale scores and age, sex and employment status. Patients with anxiety disorder scored higher on five of the seven IBQ scales compared with patients with another major disorder (mood disorder, schizophrenia or somatoform disorder). When compared with the IBQ scale scores reported in Australian patients in a psychiatric hospital, most of the IBQ scale scores differed significantly in our patients; a higher score among Japanese patients on the general hypochondriasis scale was most prominent. A similar trend in IBQ scale scores was also noted among Japanese patients visiting the hospital's general medicine clinic in comparison with Australian patients visiting a general practice clinic. Japanese patients with anxiety disorder may display the most salient abnormal illness behaviors among patients with psychiatric disorders. Sociocultural background may contribute to the characteristic abnormal illness behaviors of Japanese patients.

Adolescent↗
PubMed2000

Mu-class GSTs are responsible for aflatoxin B(1)-8, 9-epoxide-conjugating activity in the nonhuman primate macaca fascicularis liver.

Mice are resistant to the carcinogenic effects of the mycotoxin aflatoxin B(1) (AFB(1)) because they constitutively express an alpha-class glutathione S-transferase (mGSTA3-3) that has high (approximately 200,000 pmol/min/mg) activity toward aflatoxin B(1)-8, 9-epoxide (AFBO). Rats do not constitutively express a GST with high AFBO-conjugating activity and are sensitive to AFB(1)-induced hepatocarcinogenesis. Constitutively expressed human hepatic alpha-class GSTs (hGSTA1-1 and hGSTA2-2) possess little or no AFBO-detoxifying activity (<2 pmol/min/mg). Recently, we found that the nonhuman primate, Macaca fascicularis (Mf), exhibits significant (approximately 300 pmol/min/mg) constitutive hepatic GST activity towards AFBO. To determine which specific GST isoenzyme(s) is (are) responsible for this activity, MF: GSTs were purified from liver tissue and characterized and, Mf mu-class GST cDNAs were cloned by reverse transcriptase-coupled polymerase chain reaction (RT-PCR). Purification by glutathione agarose (GSHA) affinity chromatography yielded a protein, GSHA-GST, that exhibited relatively high AFBO-conjugating activity (239 pmol/min/mg) compared to other GST-containing peaks. Western blotting and enzymatic activity analyses revealed that GSHA-GST belongs to the mu class. Two distinct mu-class GST cDNAs, mfaGSTM1 (GenBank accession # AF200709) and mfaGSTM2 (GenBank accession # AF200710), were generated by RT-PCR. CDNA-derived amino acid sequence analysis revealed that mfaGSTM1 and mfaGSTM2 share 97% and 96% homology with the human mu-class GSTs hGSTM4 and hGSTM2, respectively. In contrast to recombinant mfaGSTM1-1, which had no detectable AFBO-conjugating activity, mfaGSTM2-2 exhibited this activity at 333 pmol/min/mg. Activity profiles for the stereoisomers exo- and endo-AFBO, and of 1-chloro-2,4-dinitrobenzene of the purified protein GSHA-GST and recombinant mfaGSTM2-2, suggested that they are two distinct enzymes. Our results indicate that, in contrast to rodents, mu-class GSTs are responsible for the majority of AFBO-conjugating activity in the liver of Macaca fascicularis.

Aflatoxin B1↗
PubMed2000

A peptide derived from the nonreceptor binding region of urokinase plasminogen activator (uPA) inhibits tumor progression and angiogenesis and induces tumor cell death in vivo.

Urokinase plasminogen activator (uPA) plays an important role in the progression of several malignancies including breast cancer. We have identified a noncompetitive antagonist of the uPA-uPAR interaction derived from a nonreceptor binding region of uPA (amino acids 136-143). This 8-mer capped peptide (A6) inhibited breast cancer cell invasion and endothelial cell migration in a dose-dependent manner in vitro without altering cell doubling time. Intraperitoneal administration of A6 resulted in a significant inhibition of tumor growth and suppressed the development of lymph node metastases in several models of breast cancer cell growth and metastasis. Large areas of tumor necrosis and extensive positive staining by TUNEL were observed on histological and immunohistochemical analysis of experimental tumor sections from A6-treated animals. A6 treatment also resulted in a decrease in factor VIII-positive tumor microvessel hot-spots. These results identify a new epitope in uPA that is involved in the uPA-uPAR interaction and indicate that an antagonist based on this epitope is able to inhibit tumor progression by modulating the tumor microenvironment in the absence of direct cytotoxic effects in vivo.

Amino Acid Sequence↗
PubMed2000

Variable-loop-deleted variants of the human immunodeficiency virus type 1 envelope glycoprotein can be stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits.

We have described an oligomeric gp140 envelope glycoprotein from human immunodeficiency virus type 1 that is stabilized by an intermolecular disulfide bond between gp120 and the gp41 ectodomain, termed SOS gp140 (J. M. Binley, R. W. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. J. Anselma, P. J. Maddon, W. C. Olson, and J. P. Moore, J. Virol. 74:627-643, 2000). In this protein, the protease cleavage site between gp120 and gp41 is fully utilized. Here we report the characterization of gp140 variants that have deletions in the first, second, and/or third variable loop (V1, V2, and V3 loops). The SOS disulfide bond formed efficiently in gp140s containing a single loop deletion or a combination deletion of the V1 and V2 loops. However, deletion of all three variable loops prevented formation of the SOS disulfide bond. Some variable-loop-deleted gp140s were not fully processed to their gp120 and gp41 constituents even when the furin protease was cotransfected. The exposure of the gp120-gp41 cleavage site is probably affected in these proteins, even though the disabling change is in a region of gp120 distal from the cleavage site. Antigenic characterization of the variable-loop-deleted SOS gp140 proteins revealed that deletion of the variable loops uncovers cryptic, conserved neutralization epitopes near the coreceptor-binding site on gp120. These modified, disulfide-stabilized glycoproteins might be useful as immunogens.

Amino Acid Sequence↗
PubMed2000

A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure.

The few antibodies that can potently neutralize human immunodeficiency virus type 1 (HIV-1) recognize the limited number of envelope glycoprotein epitopes exposed on infectious virions. These native envelope glycoprotein complexes comprise three gp120 subunits noncovalently and weakly associated with three gp41 moieties. The individual subunits induce neutralizing antibodies inefficiently but raise many nonneutralizing antibodies. Consequently, recombinant envelope glycoproteins do not elicit strong antiviral antibody responses, particularly against primary HIV-1 isolates. To try to develop recombinant proteins that are better antigenic mimics of the native envelope glycoprotein complex, we have introduced a disulfide bond between the C-terminal region of gp120 and the immunodominant segment of the gp41 ectodomain. The resulting gp140 protein is processed efficiently, producing a properly folded envelope glycoprotein complex. The association of gp120 with gp41 is now stabilized by the supplementary intermolecular disulfide bond, which forms with approximately 50% efficiency. The gp140 protein has antigenic properties which resemble those of the virion-associated complex. This type of gp140 protein may be worth evaluating for immunogenicity as a component of a multivalent HIV-1 vaccine.

Amino Acid Sequence↗
PubMed2000

Endothelin receptor blockade attenuates lipopolysaccharide-induced pulmonary nitric oxide production.

Increased nitric oxide (NO) synthesis by the inducible nitric oxide synthase (iNOS) has been shown to contribute to the development of acute lung injury and delayed hypotension in animals injected with bacterial lipopolysaccharides (LPS). Recent evidence indicates that endothelin-1 (ET-1) is also elevated in septic humans and in animals. To assess the contribution of ETs to LPS-induced pulmonary NO production and iNOS expression, we used P1/fl, a 22 amino acid peptide, to selectively antagonize endothelin-A receptors. Anesthetized, mechanically ventilated rats were injected with either saline or LPS (E. coli endotoxin, 20 mg/kg) and studied for 5 h. Two other groups of rats were pretreated 15 min earlier with P1/fl peptide (20 microg/kg). Unlike saline-treated rats, rats injected with LPS showed a progressive decline in arterial pressure and a significant rise in plasma ET concentration and serum nitrite-nitrate level. In the lungs, LPS injection elicited a several-fold rise in lung iNOS activity and exhaled NO concentration and increased lung wet/dry ratio significantly. Pretreatment with P1/fl peptide eliminated the decline in arterial pressure, the rise in lung wet/dry ratio, lung NOS activity, and iNOS protein expression and significantly attenuated the increase in pulmonary exhaled NO production but had no effect on plasma ET concentration. We conclude that activation of ET-A receptors by rising ET-1 concentration enhances NO production and iNOS expression in the respiratory and vascular systems and contributes to both LPS-induced hypotension and acute lung injury.

Animals↗
PubMed2000

Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy.

Despite prolonged treatment with highly active antiretroviral therapy (HAART), infectious HIV-1 continues to replicate and to reside latently in resting memory CD4(+) T lymphocytes, creating a major obstacle to HIV-1 eradication. It is therefore not surprising to observe a prompt viral rebound after discontinuation of HAART. The nature of the rebounding virus, however, remains undefined. We now report on the genetic characterization of rebounding viruses in eight patients in whom plasma viremia was undetectable throughout about 3 years of HAART. Taking advantage of the extensive length polymorphism in HIV-1 env, we found that in five patients who did not show HIV-1 replication during treatment, the rebound virus was identical to those isolated from the latent reservoir. In three other patients, two of whom had been free of plasma viremia but had showed some residual viral replication, the rebound virus was genetically different from the latent reservoir virus, corresponding instead to minor viral variants detected during the course of treatment in lymphoid tissues. We conclude that in cases with apparent complete HIV-1 suppression by HAART, viral rebound after cessation of therapy could have originated from the activation of virus from the latent reservoir. In patients with incomplete suppression by chemotherapy, however, the viral rebound is likely triggered by ongoing, low-level replication of HIV-1, perhaps occurring in lymphoid tissues.

Adult↗
PubMed2000

The heat-stable antigen determines pathogenicity of self-reactive T cells in experimental autoimmune encephalomyelitis.

Induction of myelin-specific CD4 T cells is a pivotal event in the development of experimental autoimmune encephalomyelitis (EAE). Other checkpoints in EAE pathogenesis have not been clearly defined, although multiple genetic loci are known to influence EAE development. We report here that targeted mutation of the heat-stable antigen (HSA) abrogates development of EAE despite a complete lack of effect on induction of autoimmune T cells. To test whether T-cell expression of HSA is sufficient, we created transgenic mice in which HSA is expressed exclusively in the T-cell lineage. We found that these mice remain resistant to EAE induction. Adoptive transfer studies demonstrate that both T cells and non-T cells must express HSA in order for the pathogenic T cells to execute their effector function. Moreover, HSAIg, a fusion protein consisting of the extracellular domain of the HSA and the Fc portion of immunoglobulin, drastically ameliorates the clinical sign of EAE even when administrated after self-reactive T cells had been expanded. Thus, identification of HSA as a novel checkpoint, even after activation and expansion of self-reactive T cells, provides a novel approach for immunotherapy of autoimmune neurologic diseases, such as multiple sclerosis.

Adoptive Transfer↗
PubMed2000

Physical and genetic interaction of filamin with presenilin in Drosophila.

Presenilins were first identified as causative factors in early onset, familial Alzheimer's Disease (FAD). They are predicted to encode a highly conserved novel family of eight transmembrane domain proteins with a large hydrophilic loop between TM6 and TM7 that is the site of numerous FAD mutations. Here, we show that the loop region of Drosophila and human presenilins interacts with the C-terminal domain of Drosophila filamin. Furthermore, we show that Drosophila has at least two major filamin forms generated by alternative splicing from a gene that maps to position 89E10-89F4 on chromosome 3. The longest form is enriched in the central nervous system and ovaries, shares 41.7% overall amino acid identity with human filamin (ABP-280) and contains an N-terminal actin-binding domain. The shorter form is broadly expressed and encodes an alternatively spliced form of the protein lacking the actin-binding domain. Finally, we show that presenilin and filamin are expressed in overlapping patterns in Drosophila and that dominant adult phenotypes produced by overexpression of presenilin can be suppressed by overexpression of filamin in the same tissue. Taken together, these results suggest that presenilin and filamin functionally interact during development.

Alternative Splicing↗
PubMed2000

Cell proliferation and apoptosis in prostate cancer: significance in disease progression and therapy.

Recent biochemical and genetic studies have substantially increased our understanding of death signal transduction pathways, making it clear however, that apoptosis is not a single-lane, one-way street. Rather, multiple parallel pathways have been identified. For instance, analysis of bcl-2, bax, p53, and caspase knockout mice while establishing distinct roles for each of these apoptotic players, they also provided valuable information for the design of specific inhibitors of apoptosis. Thus blocking one pathway, as in caspase knockout mice, what we observe is not a complete suppression of apoptosis but rather a delay in apoptosis induction (Hakem et al., 1998; Kuida et al., 1998). In view of nature's means of ensuring activation of a compensatory apoptotic response, when one pathway fails in developing prostate cancer therapeutic interventions, the challenge remains to further dissect individual apoptotic pathways. Advances in our understanding of the integrated functions governing prostate cell proliferation and cell death, clearly suggest that effective prostate cancer therapies are not only molecularly targeted, but that are also customized to take into account the delicate balance of opposing growth influences in the ageing gland. In this review we discuss the evidence on the significance of molecular deregulation of the key players of this growth equilibrium, apoptosis and cell proliferation in prostate cancer progression, and the clinical implications of changes in the apoptotic response in disease detection and therapy.

Animals↗
PubMed2000

[Expression and immunological reactivity of recombinant HCV-core protein].

OBJECTIVE: To express HCV-core proteins in E.coli and to develop effective HCV-core DNA-based vaccine. METHODS: The vector that expresses the highly conserved HCV core genes were constructed. The pGEX-3X HCVCore constructs contained the 1-201 ncls (1-67aa, C201), 1-402 ncls (1-134aa, C402) and 1-591ncls ( 1-197aa, C591), then expressed in E.coli cells. RESULTS: The products of HCV C201 and C402 genes were expressed as a fusion protein with glutathione-S-transferase (GST, 26kDa) whose molecular weight were 3.1 x 10(4) and 3.9 x 10(4) separately. C591 gene was not effectively expressed in E.coli. The expressed proteins were sequestered within inclusion bodies (IB) and a variety of procedures designed to minimize IB formation proved unsuccessful. The method finally adopted involved the purification of inclusion bodies followed by the solubilization, purification, and refolding of the expressed protein. The purified C402 protein was antigenically reactive with serum from chronically infected HCV patients. BALB/C mice were immunized by a subcutaneous injection of C402 protein together with Freund's complete adjuvant which produced strong anti-HCV core humoral immune responses. CONCLUSION: It is important for the study of gene vaccine to construct a certain length of HCV core gene.

Animals↗
PubMed2000

[Cytogenetics and clinical studies of hematologic malignancies with 11q23 abnormalities in China].

OBJECTIVE: To evaluate the association between 11q23 abnormalities and the clinical, hematologic, prognostic aspects of hematologic malignancies. METHODS: A total of 6000 cases of hematologic malignancies from our hospital and near regions in China were investigated between October 1985 and November 1998. Chromosome preparations were made on bone marrow cells by using direct method and/or unstimulated short-term cultures. Karyotypes were analyzed by R-banding technique and expressed according to ISCN(1995). RESULTS: 11q23 abnormalities were found in 28 of 6000 cases with hematologic malignancies(0.47%). It may be separated into seven cytonetic categories: t(4;11)(q21;q23)(ten cases), t(11;19)(q23;p13)(five cases), t(9;11)(p12;q23)(two cases), t(10;11)(p15;q23)(two cases), t(6;11)(q27;q23) (one case), del(11)(q23)(seven cases), and t(11;?)(q23;?)(one case). The diagnoses included acute myeloid leukemia in 14 cases (M(2a), three; M(4), two; M(5a), one; M(5b), eight), acute lymphoblastic leukemia(ALL) in 10 cases, myelodysplastic syndrome in three cases and malignant histiocytosis in one case. All 10 cases with t(4;11) anomaly were ALL. Follow-up data were available for 22 of them. Their median survival was 113 days. The patients may be grouped according to the presence or absence of additional abnormalities and/or normal karyotype. The median survival was 75 days for five patients with 11q23 anomaly only, 18 days for two patients with 11q23 and additional abnormalities, 135 days for 10 patients with 11q23 anomaly, additional abnormalities and normal karyotype, and 150 days for 5 patients with 11q23 anomaly and normal karyotype. CONCLUSION: 11q23 abnormalities were mainly seen in ALL and acute monocytic leukemia. Their prognosis was very poor. Both additional abnormalities and lack of normal karyotype had adverse effects on the survival of patients. Thus, they represent a unique clinical-cytogenetic association. 11q23 abnormality; hematologic malignancy; acute monocytic leukemia; acute lymphoblastic leukemia; prognosis

Adolescent↗
PubMed2000

Genetic heterogeneity of non-specific mental retardation.

OBJECTIVE: To explore genetic patterns of non-specific mental retardation (NSMR). METHODS: Using segregation analysis, Finney method and Falconer method, the authors studied 157 pedigrees with NSMR selected in a population survey in Shandong province. RESULTS: Ux U multiplex families may accept the autosomal recessive inheritance, Ux U total families is the autosomal recessive inheritance while it may be the multifactorial inheritance with major-gene effect, the frequency of sporadic cases is approximately 46%; Ux A mating families may keep the incomplete penetrance in autosomal dominant inheritance. CONCLUSION: The genetic pattern of NSMR has the genetic heterogeneity.

Female↗
PubMed2000

Linkage of the genes controlling natural killer cell activity to HLA-B.

OBJECTIVE: To study whether there is a relationship between HLA-B alleles and low natural killer(NK) cell activity in Chinese. METHODS: The subjects were 34 unrelated healthy individuals (10 males and 24 females), aged 25-60 years, and 31 individuals (17 males and 14 females) from 11 families, aged 22-70 years, previously genotyped for HLA class I, II, complotypes and haplotypes that were assigned based on family studies. The unrelated individuals were typed for HLA-A, -B antigen by a microcytotoxicity assay and all the subjects were tested for NK cell activity by lactate dehydrogenase (LDH) enzyme-release assay. RESULTS: Statistical analysis showed that 30 lysis unit(LU) was the cutoff value of low and high NK reactors. The frequency of low reactor individuals homozygous for HLA-B was significantly higher than that for those for HLA-DR(P< 0. 05). The associated genes included HLA-B13, B40, B46, B7, B57, defined as NKB1 genes, and HLA-B44 as NKB2 gene. Family studies provide further evidence that the genes controlling low NK cell activity were located in the MHC region and it was a recessive trait. CONCLUSION: There were recessive genes associated with HLA-B controlling low NK cell activity in Chinese. The NKB alleles were partly different from those found in Caucasian.

Adult↗
PubMed2000

Secondary near-pentaploidy and/or near-tetraploidy characterized by the duplication of 8;21 translocation in the M2 subtype of acute myeloid leukemia.

Hyperploidy, especially near-tetraploidy, is rare in acute myeloid leukemia (AML). We report 2 cases with secondary hyperploidy characterized by double 8;21 translocations. Morphologic observation of bone marrow smears revealed numerous giant blasts in both cases. Chromosome analyses with R-banding technique showed a karyotype of 46,XX,t(8;21)(2%)/92,XXXX, add(7)(q31)x2,t(8;21)x2(7%)/100-117,XXX,-X,-X,-1,+4,+4,-7,+add(7)(q31)x3 , t(8;21)x2,+der(21)t(8;21),+22(90.6%)/46,XX(0.3%) in case 1 and a karyotype of 45,X,-Y,t(8;21)(15%)/90,XX,-Y,-Y,t(8;21)x2(80%)/46,XY(5%) in case 2. DNA ploidy analyses by flow cytometry showed triple peaks (diploid, tetraploid [DI 2.09] and near-pentaploid [DI 2.59]) in case 1, and double peaks (diploid and near-tetraploid [DI 2.07]) in case 2. Reverse-transcriptase polymerase chain reaction detected an AML1/ETO fusion transcript (152 bp) in both cases. This paper brings the total number of cases of secondary hyperploid t(8;21) AML to 6 and further emphasizes a correlation between hyperploidy and t(8;21) translocation.

Bone Marrow↗
PubMed2000

[The application of competitive RT-PCR to detect minimal residual disease in patients with 8;21 translocation].

OBJECTIVE: To construct and evaluate the competitive quantitative RT-PCR method for detecting the fusion gene of AML1-ETO in the patients of t(8;21)AML(acute myeloid leukemia). METHODS: The authors used the method of splicing by overlapping extension (SOE) to obtain the competitive DNA fragment, with which they set up the competitive quantitative RT-PCR assay to detect AML1-ETO chimeric genes in the patients of t(8;21) AML. RESULTS: The competitive DNA fragment has been obtained; the sensitive competitive RT-PCR method is developed, which allows the quantitation of the number of AML1-ETO transcriptions in t(8;21)AML patients at different phases. CONCLUSION: The competitive quantitative RT-PCR method, based on SOE, is simple and convenient; t(8;21) AML patients in different survival conditions express AML1-ETO gene quite differently.

Chromosomes, Human, Pair 21↗