Biomedical subjects

Y Zhang

Publications and source records attributed to Y Zhang.

At least 397 records · Page 22Linked to original sources

PubMed2001

Mammalian sweet taste receptors.

The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery.

Animals↗

PubMed2001

Scurfin (FOXP3) acts as a repressor of transcription and regulates T cell activation.

We have recently identified and cloned Foxp3, the gene defective in mice with the scurfy mutation. The immune dysregulation documented in these mice and in humans with mutations in the orthologous gene indicates that the foxp3 gene product, scurfin, is involved in the regulation of T cell activation and differentiation. The autoimmune state observed in these patients with the immune dysregulation polyendocrinopathy, enteropathy, X-linked syndrome, or X-linked autoimmunity-allergic dysregulation syndrome also points to a critical role for scurfin in the regulation of T cell homeostasis. FOXP3 encodes a novel member of the forkhead family of transcription factors. Here we demonstrate that this structural domain is required for nuclear localization and DNA binding. Scurfin, transiently expressed in heterologous cells, represses transcription of a reporter containing a multimeric forkhead binding site. Upon overexpression in CD4 T cells, scurfin attenuates activation-induced cytokine production and proliferation. We have identified FKH binding sequences adjacent to critical NFAT regulatory sites in the promoters of several cytokine genes whose expression is sensitive to changes in SFN abundance. Our findings indicate that the ability of scurfin to bind DNA, and presumably repress transcription, plays a paramount role in determining the amplitude of the response of CD4 T cells to activation.

Animals↗

PubMed2001

The tropism of organ involvement in primary systemic amyloidosis: contributions of Ig V(L) germ line gene use and clonal plasma cell burden.

Primary systemic amyloidosis (AL) is a protein conformation disorder in which monoclonal immunoglobulin light chains produced by clonal plasma cells are deposited as amyloid in the kidneys, heart, liver, or other organs. Why patients with AL present with amyloid disease that displays such organ tropism is unknown. This study tested the hypothesis that both the light-chain variable region (Ig V(L)) germ line genes used by AL clones and the plasma cell burden influenced AL organ tropism. To assess the renal tropism of some light chains, an in vitro renal mesangial cell model of amyloid formation was used. With reverse transcription-polymerase chain reaction, Ig V(L) genes were sequenced from 60 AL patients whose dominant involved organs were renal (52%), cardiac (25%), hepatic (8%), peripheral nervous system (8%), and soft tissue and other (7%). Patients with clones derived from the 6a V(lambdaVI) germ line gene were more likely to present with dominant renal involvement, whereas those with clones derived from the 1c, 2a2, and 3r V(lambda) genes were more likely to present with dominant cardiac and multisystem disease. Patients with V(kappa) clones were more likely to have dominant hepatic involvement and patients who met the Durie criteria for myeloma (38%, 23 of 60) were more likely to present with dominant cardiac involvement independent of germ line gene use. In the in vitro model, unlike all other AL light chains tested, lambdaVI light chains formed amyloid rapidly both with and without amyloid-enhancing factor. These data support the hypothesis that germ line gene use and plasma cell burden influence the organ tropism of AL. (Blood. 2001;98:714-720)

Adult↗

PubMed2001

Efficient introduction of protected guanidines in boc solid phase peptide synthesis.

[reaction: see text] Reaction of primary amines with pyrazole 1 results in rapid and efficient guanidinylation, either in solution or on solid phase. The reaction affords sulfonamide-protected products required for BOC solid phase peptide synthesis (SPPS) in a single step under mild conditions. Incorporation of orthogonally protected side chain amines permits the synthesis of peptides containing arginine analogues, one of which could not be prepared by coupling of preformed amino acids.

Amines↗

PubMed2001

Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents.

With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.

Amides↗

PubMed2001

Glibenclamide's action in the hypothalamus alters peripheral glucose homeostasis.

Bilateral injections of 0.2 nmol of glibenclamide, targeted at the ventromedial hypothalamus of albino rats, significantly impaired recovery of blood glucose levels following insulin-induced hypoglycemia (P=0.0026). Similar injections of 0.2 and 2.0 nmol glibenclamide reduced blood glucose by 23.6 and 40.8 mg%, respectively, in otherwise untreated rats (P<0.01 and P<0.001). Intravenous injection of these doses of the drug did not lower blood glucose. The results support the hypothesis that K(ATP)(+) channels within the hypothalamus serve a counterregulatory function in the maintenance of peripheral glucose levels.

Animals↗

PubMed2001

Indian hedgehog is an essential component of mechanotransduction complex to stimulate chondrocyte proliferation.

Indian hedgehog (Ihh), a member of the vertebrate hedgehog morphogen family, is a key signaling molecule that controls chondrocyte proliferation and differentiation. In this study, we show a novel function of Ihh. Namely, it acts as an essential mediator of mechanotransduction in cartilage. Cyclic mechanical stress greatly induces the expression of Ihh by chondrocytes. This induction is abolished by gadolinium, an inhibitor of stretch-activated channels. This suggests that the IHH gene is mechanoresponsive. The mechano-induction of Ihh is essential for stimulating chondrocyte proliferation by mechanical loading. The presence of an Ihh functional blocking antibody during loading completely abolishes the stimulatory effect of mechanical load on proliferation. Furthermore, Ihh mediates the mechanotransduction process in a bone morphogenic protein (BMP)-dependent and parathyroid hormone-related peptide-independent manner. BMP 2/4 are up-regulated by mechanical stress through the induction of Ihh, and BMP antagonist noggin inhibits mechanical stimulation of chondrocyte proliferation. This suggests BMP lies downstream of Ihh in mechanotransduction pathway. Our data suggest that Ihh may transduce mechanical signals during cartilage growth and repair processes.

Animals↗

PubMed2001

Spin-ordering quantum transitions of superconductors in a magnetic field.

We argue that recent neutron scattering measurements by Lake et al. [Science 291, 1759 (2001)] of the spin excitation spectrum of La(2-delta)Sr(delta)CuO4 in a magnetic field can be understood in terms of proximity to a phase with co-existing superconductivity and spin density wave order. We present a general theory for such quantum transitions, and argue that their low energy spin fluctuations are controlled by a singular correction from the superflow kinetic energy, acting in the region outside the vortex cores. We propose numerous experimental tests of our theory.

Journal Article↗

PubMed2001

Interferon gamma stabilizes the T helper cell type 1 phenotype.

T helper cell (Th)1-primed CD4 T cells from wild-type donors make little interleukin (IL)-4 when restimulated under Th2 conditions. However, such restimulation of Th1-primed cells from interferon (IFN)-gamma(2/-) or IFN-gamma receptor (IFN-gammaR)(-/-) mice resulted in substantial production of IL-4 and other Th2 cytokines. Adding IFN-gamma to the priming culture markedly diminished the capacity of Th1-primed IFN-gamma(2/-) cells to express IL-4. Even IFN-gamma-producing cells from IFN-gammaR(-/-) mice could acquire IL-4-producing capacity. Thus, IFN-gamma is not required for the development of IFN-gamma-producing capacity, but it plays a critical role in suppressing the IL-4-producing potential of Th1 cells.

Animals↗

PubMed2001

CV706, a prostate cancer-specific adenovirus variant, in combination with radiotherapy produces synergistic antitumor efficacy without increasing toxicity.

Radiation is an effective means of treating localized prostate cancer. However, up to 40% of men with certain risk factors will develop biochemical failure 5 years after radiotherapy. CV706, a prostate cell-specific adenovirus variant, is currently in clinical trials for the treatment of recurrent organ-confined prostate cancer. We demonstrated previously that a single administration of CV706 at 5 x 10(8) particles/mm3 of tumor eliminated established tumors within 6 weeks in nude mouse xenografts (Rodriguez et al., Cancer Res. 57: 2559-2563, 1997). We now demonstrate that CV706-mediated cytotoxicity is synergistic with radiation. In vitro, addition of radiation to CV706 resulted in a synergistic increase of cytotoxicity toward the human prostate cancer cell line LNCaP and a significant increase of virus burst size, with no reduction in specificity of CV706-based cytopathogenicity for prostate cancer cells. In vivo, prostate-specific antigen (+) LNCaP xenografts of human prostate cancer were treated with CV706 (1 x 10(7) particles/mm3 of tumor), 10 Gy of single fraction local tumor radiation, or both. Tumor volumes of the group treated with CV706 or radiation was 97% or 120% of baseline 6 weeks after treatment. However, when the same dose of CV706 was followed 24 h later with the same dose of radiation, the tumor volume dropped to 4% of baseline at this time point and produced antitumor activity that was 6.7-fold greater than a predicted additive effect of CV706 and radiation. Histological analyses of tumors revealed that, compared with CV706 or radiation alone, combination treatment with two agents increased necrosis by 180% and 690%, apoptosis by 330% and 880%, and decreased blood vessel number by 1290% and 600%, respectively. Importantly, no increase in toxicity was observed after combined treatment when compared with CV706 or radiation alone. These data demonstrate that CV706 enhances the in vivo radioresponse of prostate tumors and support the clinical development of CV706 as a neoadjuvant agent with radiation for localized prostate cancer.

Adenoviridae↗

PubMed2001

Identification and characterization of GDP-d-mannose 4,6-dehydratase and GDP-l-fucose snthetase in a GDP-l-fucose biosynthetic gene cluster from Helicobacter pylori.

In this study two open reading frames, namely HP0044 and HP0045 from H. pylori, were cloned and overexpressed in E. coli. The two recombinant proteins were demonstrated to have GDP-d-mannose 4,6-dehydratase (GMD) and GDP-l-fucose synthetase (GFS) activities, respectively. The recombinant GMD was a tetramer and had an optimum pH of 6.5. Exogenous NADP(+) was essential for its activity. The K(m) and K(cat) for GDP-d-mannose were 117.3 microM and 0.27 s(-1), respectively. The recombinant GFS was a homodimer with an optimum pH of 8.0. The K(m) and K(cat) for GDP-4-keto-6-deoxy-d-mannose were 64.08 microM and 0.75 s(-1), respectively. It can use both NADPH and NADH, but less efficient with the latter. Amino acid sequence alignment and phylogenetic analysis showed that H. pylori GFS was highly homologous to the GFS of E. coli O111 and both of them were located on a separate phylogenetic branch from other GFS. The unique clustering and origin of the two genes were also discussed.

Amino Acid Sequence↗

PubMed2001

Migration of neutral solutes by double stepwise gradient elution in capillary electrochromatography.

Characteristics of electroosmotic flow (EOF) and the migration of neutral solutes under double stepwise gradient elution in capillary electrochromatography were studied systematically. EOF velocity proved to be the function of operation time changing with the introduction of the second mobile phase. Accordingly, the retention of components also changed. The migration of neutral solutes was studied under the following three situations; A, components eluted when the column was filled only with the first kind of mobile phase; B, solutes eluted still in the first kind of mobile phase while at that time two kinds of mobile phase coexisted in the column and C, samples eluted in the second kind of mobile phase. Equations to describe the retention times of components under these three kinds of conditions were deduced and applied to predict the retention times of 12 aromatic compounds. Relative errors between experimental and calculated values were below 5.0%, which proved the reliability of the equations. In addition, parameters that might affect the retention time of solutes, such as the transferring time of mobile phase vials, the capacity factors of components and EOF velocities two steps were studied systematically.

Chromatography, Micellar Electrokinetic Capillary↗

PubMed2001

[Clinical characteristics and treatment of midline nasal and nasal type NK/T cell lymphoma].

OBJECTIVE: To study the clinical characteristics and treatment of midline nasal and nasal type T/Nk cell non-Hodgkin lymphoma. METHODS: A retrospective study was made on the clinical characteristics, treatment, short-term effect, and two-year survival rate of 37 patients with midline nasal and nasal type T/NK non-Hodgkin lymphoma. RESULTS: All of the patients were primarily treated with 2 cycles of CHOP chemotherapy. Ten of them were with good effect (common group). Then they were given 6 cycles of chemotherapy followed by focal radiotherapy and reached complete remission (CM). The other 27 patients failed to reach partial remission (PM) or even with their condition worsened after 2 cycles of CHOP regimen and were included into the refractory group. Fourteen of them received L-asparaginase-based salvage chemotherapy followed by focal radiotherapy (L-ASP group), and salvage therapy without L-ASP and followed by focal radiotherapy was given to the other 13 patients (non-L-ASP group). Continuous fever, angioinvasive growth and necrotic lesion could not be found among the patients in the common group. Their international prognostic indexes (IPI) were 0 approximately 1. Seventy percent of them were at the stages I or II. Continuous fever, angioinvasive growth and necrotic lesion could be found in the patients in refractory group. The IPIs among 85% of them were > 2, and 82% of them were at the stages III and IV. The CR rate was 46% for all patients as a whole, 100% for the common group, 26% for the refractory group (P < 0.005); and was 50% for the L-ASP group and 0% for the non-L-ASP group (P < 0.005). The 2-year survival rate was 43% for all patients as a whole, 100% for the common group, 20% for the refractory group (P < 0.005); and was 50.8% for the L-ASP group and 0% for the non-L-ASP group (P < 0.005). CONCLUSION: Patients with midline nasal and nasal type T/NK non-Hodgkin lymphoma can be treated primarily by CHOP regimen and local radiotherapy. Refractory patients can be treated by salvage therapy based on L-ASP chemotherapy with a rather good effect. The clinical characteristics of most of the refractory patients include continuous fever, angioinvasive growth, necrotic lesion, being at stage III and IV, and with an IPI > 2.

Adolescent↗

PubMed2001

[Helicobacter pylori associated gastric mucosal inflammation and histopathological assessment].

OBJECTIVE: To investigate the pathological features of Helicobacter pylori associated gastric mucosal inflammation and to establish relevant histopathological assessment standards. METHODS: Biopsy specimens from the gastric antrum, body of stomach, and gastric angle were taken from 2 134 cases of H. pylori associated gastric mucosal inflammation. H. pylori was identified by means of rapid urase test and toluidine blue staining or immunohistological staining. The severity of mucosal inflammation was evaluated with HE staining. Ultrastucture evaluation was conducted for part of the specimens. RESULTS: In H. pylori positive cases lymphocytic infiltration could be observed in glandulous epithelium. which was not found in normal gastric mucosa. Scoring of severity of mucosal inflammation reflected the status of H. pylori infection and was not influenced by the biopsy site, size of specimen, and direction of sectioning. Severe active inflammation could be seen in 39.6% of the H. pylori positive cases, and 0.4% of the H. pylori negative cases. The severity score of inflammation was significantly correlated with the amount of H. pylori colonization. CONCLUSION: Reflecting the real status of H. pylori associated mucosal inflammation. The grading method reported here is simple, reliable, and easy to master.

Adolescent↗

PubMed2001

Intron conservation in the DNA polymerase gene encoded by Chlorella viruses.

Previously we reported that 19 of 42 viruses that infect Chlorella strain NC64A (NC64A viruses) contain a short, nuclear-located, spliceosomal-processed intron in a pyrimidine dimer-specific glycosylase/apyrimidine lyase (pdg) gene. Surprisingly, the nucleotide sequence of the intron region is more conserved than the exon regions of the gene (L. Sun et al., 2000, J. Mol. Evol. 50, 82-92). For comparative purposes, we determined the nucleotide sequence of a similar intron type and its flanking coding regions in the DNA polymerase (dnapol) gene from the same 42 NC64A viruses and also 5 viruses that infect Chlorella strain Pbi. Thirty-eight of the 42 NC64A viruses contained a 101-nucleotide intron and the remaining 4 had an 86-nucleotide intron located in the same position in dnapol. The 4 viruses with the smaller intron in dnapol also have a smaller intron in their pdg gene. There was no intron in the dnapol gene of the 5 Pbi viruses. Phylogenetic analyses indicate that the dnapol genes containing the 86-nucleotide intron represent the ancestral condition among the NC64A viruses. The intron in the dnapol gene is phase 0 (keeps codons intact), which differs from the phase 1 intron in the pdg gene. The intron in the dnapol gene, unlike the pdg intron, was conserved (83 to 100% identical) to about the same extent as the coding regions of the gene (78 to 100% identical).

Amino Acid Sequence↗

PubMed2001

Molecular cloning and characterization of chemokine-like factor 1 (CKLF1), a novel human cytokine with unique structure and potential chemotactic activity.

Cytokines are small proteins that have an essential role in the immune and inflammatory responses. The repertoire of cytokines is becoming diverse and expanding. Here we report the identification and characterization of a novel cytokine designated as chemokine-like factor 1 (CKLF1). The full-length cDNA of CKLF1 is 530 bp long and a single open reading frame encoding 99 amino acid residues. CKLF1 bears no significant similarity to any other known cytokine in its amino acid sequence. Expression of CKLF1 can be partly inhibited by interleukin 10 in PHA-stimulated U937 cells. Recombinant CKLF1 is a potent chemoattractant for neutrophils, monocytes and lymphocytes; moreover, it can stimulate the proliferation of murine skeletal muscle cells. These results suggest that CKLF1 might have important roles in inflammation and in the regeneration of skeletal muscle.

Amino Acid Sequence↗

PubMed2001

Reproducible and inexpensive probe preparation for oligonucleotide arrays.

We present a new protocol for the preparation of nucleic acids for microarray hybridization. DNA is fragmented quantitatively and reproducibly by using a hydroxyl radical-based reaction, which is initiated by hydrogen peroxide, iron(II)-EDTA and ascorbic acid. Following fragmentation, the nucleic acid fragments are densely biotinylated using a biotinylated psoralen analog plus UVA light and hybridized on microarrays. This non-enzymatic protocol circumvents several practical difficulties associated with DNA preparation for microarrays: the lack of reproducible fragmentation patterns associated with enzymatic methods; the large amount of labeled nucleic acids required by some array designs, which is often combined with a limited amount of starting material; and the high cost associated with currently used biotinylation methods. The method is applicable to any form of nucleic acid, but is particularly useful when applying double-stranded DNA on oligonucleotide arrays. Validation of this protocol is demonstrated by hybridizing PCR products with oligonucleotide-coated microspheres and PCR amplified cDNA with Affymetrix Cancer GeneChip microarrays.

Ascorbic Acid↗

PubMed2001

[Influence of cytokine gene polymorphism on renal transplantation].

OBJECTIVE: To investigate the influence of cytokine gene polymorphism on renal transplantation. METHODS: The cytokine genotypes of cytokines TNF-alpha, IL-10, TGF-beta(1), and L-6 among 91 consecutive kidney recipients were detected by PCR-SSP. The distribution frequencies of different cytokine genotypes and the influence of cytokine gene polymorphism on renal transplantation were analyzed. RESULTS: Among the 91 renal recipients, the dominant genotypes of IL-10 and TNF-alpha were low producer genotype with the frequencies of 90.1% and 79.1% respectively; and the dominant genotypes of TGF-beta(1) and IL-6 were high producer genotypes (79.1% and 100% respectively). The kidney recipients with TNF-alpha high producer genotype and IL-10 high or intermediate producer genotype were associated with more acute rejection episodes than those with low producer genotypes. The acute rejection episodes in the kidney recipients with IL-10 high or intermediate producer genotype were mainly vascular acute rejection. CONCLUSION: The cytokine gene polymorphism has significant influence on incidence and severity of acute rejection after renal transplantation. Detecting the cytokine genotype before renal transplantation is beneficial to predict the outcome of transplantation accurately.

Adolescent↗