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Biomedical subjects

Y Tang

Publications and source records attributed to Y Tang.

At least 73 records · Page 4Linked to original sources

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↗

Unbiased stereological quantification of neurons in the human spiral ganglion.

We applied an unbiased stereological technique, the optical fractionator, on five human archival temporal bone specimens to estimate the total number of spiral ganglion neurons. Available archival human temporal bone specimen has been serially sectioned at 20 microm and every tenth section was stained. All the stained sections passing through the spiral ganglion were used for the analysis. From each section sampled, the counting areas were systematically randomly sampled within the sectional area of the spiral ganglion. The neurons within the counting areas sampled were counted with the optical disector technique. The total number of the human spiral ganglion neurons was estimated by multiplying the number of neurons counted by the reciprocal of the aggregate sampling fraction. We found an average of 41700 neurons with a coefficient of variation of 0.14, which is a significant departure from the previously published data obtained with the assumption-based methods. The mean coefficient of error for the stereological estimates of the total number of human spiral ganglion neurons was 0.078. The present report presents unbiased stereological sampling and counting strategies for the future quantitative studies on the spiral ganglion neurons. The result of the present study provides the first unbiased baseline value of the human spiral ganglion neurons.

Adult↗

[Establishment of method for determining serum beta-hydroxybutyric acid and its meaning in diabetes ketosis acidism].

OBJECTIVE: This study was to establish enzyme-rate method for determining serum beta-hydroxybutyric acid, and to discuss its meaning in diabetes ketosis acidism. METHODS: Enzyme-rate method was used to determine serum beta-hydroxybutyric acid in 60 cases of normals, 30 cases of diabetes, and 8 cases of ketosis acidism by Hitachi 7170A autochemistry analyzer. RESULTS: The recovery rate is 108%, the linerity extent 0-4.0 mmol.L-1, the coefficient of variation within-run is 2.2% and day-to-day is 2.6%. CONCLUSION: The enzyme-rate method for determining serum beta-hydroxybutyric acid save time, gives accurate results and has wide linerity, so it can used for diagnosis of diabetes ketosis acidism.

3-Hydroxybutyric Acid↗

Age-related change in the number of neurons in the human vestibular ganglion.

Dysequilibrium of aging in humans has been speculated to arise from progressive deterioration within anatomical components of the vestibular system. An integral part of this system is vestibular ganglions, which are bipolar neurons that relay peripheral vestibular information to the central nervous system. To assess the effect of aging on the number of human vestibular ganglion neurons, assumption-free stereology in the form of the optical fractionator was used on 20 serially sectioned archival human temporal bone specimens. Donors had no history of vestibular pathology and ranged in age from 2 to 88 years. An average of 25,812 (coefficient of variation = 0.13) vestibular ganglion neurons was found throughout this age range, a significant departure from the results of past studies. Logistics-based regression analysis pointed to a nonlinear pattern of decline in the neuronal population: the number of cells remained roughly constant at about 28,952 cells in youth and then declined gradually between 30 and 60 years of age before leveling off at approximately 23,349 cells in older individuals. This study confirmed the existence of an age-related decline in the primary neurons of the human vestibular system, thus providing one anatomical basis for the increased incidence of imbalance seen with age.

Adolescent↗

Increased inwardly rectifying potassium currents in HEK-293 cells expressing murine transient receptor potential 4.

Drosophila transient receptor potential (Trp) and its mammalian homologues are postulated to form capacitative Ca2+ entry or store-operated channels. Here we show that expression of murine Trp4 in HEK 293 cells also leads to an increase in inwardly rectifying K+ currents. No similar increase was found in cell lines expressing Trp1, Trp3 or Trp6. Consistent with typical characteristics of inward rectifiers, the K+ currents in Trp4-expressing cells were blocked by low millimolar concentrations of Cs+ and Ba2+, but not by 1.2 mM Ca2+, and were only slightly inhibited by 5 mM tetraethylammonium. Single channel recordings of excised inside-out patches revealed the presence of two conducting states of 51 pS and 94 pS in Trp4-expressing cells. The outward current in the excised patches was blocked by 1 mM spermine, but not by 1 mM Mg2+. How Trp4 expression causes the increase in the K+ currents is not known. We propose that Trp4 either participates in the formation of a novel K+ channel or up-regulates the expression or activity of endogenous inwardly rectifying K+ channels.

Animals↗

X-Ray study on an artificial mung bean inhibitor complex with bovine beta-trypsin in neat cyclohexane.

The active trypsin inhibiting component, SPC1, was obtained during the synthesis of a 22-residue peptide with three disulfide bridges according to the mimic mung bean Bowman-Birk type inhibitor. The K(i) value of SPC1 is 1.2x10(-7) M. In order to determine the topological structure of SPC1, X-ray diffraction studies were carried out on the complex of SPC1 with bovine beta-trypsin. Only the binding loop of SPC1 resolved at 2.2 A resolution due to conformational flexibility of the other residues [1]. The amino acid sequence was re-determined and electrospray mass spectroscopy was also performed to ensure that no cleaving occurred on SPC1 and the primary sequence of SPC1 is correct. Because the protein is more rigid in nonaqueous medium as has been proved by others [2], we treated the complex of SPC1 with neat cyclohexane and then subjected it to X-ray diffraction analysis, and the result showed that all the 22 residues of SPC1 were located in the electron density map. So the topological structure of SPC1 has been determined, suggesting that crystal treatment with cyclohexane may be used as a method to determine the conformation of the disordered regions in protein crystal structures.

Amino Acid Sequence↗

Stabilization of coiled-coil peptide domains by introduction of trifluoroleucine.

Substitution of leucine residues by 5,5,5-trifluoroleucine at the d-positions of the leucine zipper peptide GCN4-p1d increases the thermal stability of the coiled-coil structure. The midpoint thermal unfolding temperature of the fluorinated peptide is elevated by 13 degrees C at 30 microM peptide concentration. The modified peptide is more resistant to chaotropic denaturants, and the free energy of folding of the fluorinated peptide is 0.5-1.2 kcal/mol larger than that of the hydrogenated form. A similarly fluorinated form of the DNA-binding peptide GCN4-bZip binds to target DNA sequences with affinity and specificity identical to those of the hydrogenated form, while demonstrating enhanced thermal stability. Molecular dynamics simulation on the fluorinated GCN4-p1d peptide using the Surface Generalized Born implicit solvation model revealed that the coiled-coil binding energy is 55% more favorable upon fluorination. These results suggest that fluorination of hydrophobic substructures in peptides and proteins may provide new means of increasing protein stability, enhancing protein assembly, and strengthening receptor-ligand interactions.

Amino Acid Sequence↗

[Using L-form bacterium ATP bioluminescence assay for rapid testing L-form bacterial susceptibility].

Adenosine triphosphate is a kind of necessary metabolites in living cells. The authors detected ATP contents by using bioluminescence method in 111 strains of L-form bacteria after exposing to 5 kinds of antibiotics. The results showed that the mean value of CPM was less than (35 +/- 10.2)%.s-1. Thus, the value could be acted as a critical concentration between susceptibility and resistance. The conincidence rate of this method and K-B method was 95.3%. It indicates that the bioluminescence method has a high sensitivity. It can be used to detect L-form bacterium-drug susceptibility quickly and may play an important role for choosing the antibiotics.

Adenosine Triphosphate↗

[Analysis of 2200 kidney transplantations].

OBJECTIVE: To analyze the clinical results of 2 200 renal transplantations. METHODS: The following factors were analyzed: (1) the graft survival rates at 1, 3 and 5 years; (2) main factors contributing to the mortality; (3) factors affecting the survival rate of retransplant grafts; (4) features of cancers after renal transplantation; (5) effect of CSA on liver function after renal transplantation; (6) treatments for chronic rejection; and (7) effect of HLA typing on renal transplantation. RESULTS: From 1972 to 2000, 2 200 renal transplantations were performed in 1 908 patients (1 337 men and 571 women) with end-stage renal failure in our hospital, Beijing. The graft survival rates at 1, 3 and 5 years were 87.3%, 80.2% and 67.0% respectively, after using CSA since 1985. 302 recipients were aged over 50 years whose one year graft survival rate was 83.4% and one year patient survival rate was 85.4%. Pneumonitis was the dominant death factor after renal transplantation, with an incidence of 4.49% and a death rate of 34.62%. The incidence of positive CMV after renal transplantation was up to 40.3%, in with a death rate of 8.0%. The incidence of tumor after renal transplantation was 1.5%. The most frequent site of tumor was urological system. The patient's liver function before transplantation and the intraindividual variability of bioavailabity to CSA etc. were the major toxic factors of the liver. The incidences of acute rejection were 27%, 35.5%, 22.4%, 20.85%, 0% and 0%, respectively, when the HLA mismatches were 6, 5, 4, 3, 2 and 1. CONCLUSION: Using immunosuppressents reasonably, preventing acute rejection, and achieving good HLA typing are the major factors improving long-term graft/patient survival rate.

Adolescent↗

Substantial differences in specificity of HIV-specific cytotoxic T cells in acute and chronic HIV infection.

Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human viral infections. Most studies in human infections have focused on CTL specificities in chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute infection. In this study, HIV-1 infection in persons expressing human histocompatibility leukocyte antigen (HLA)-A*0201 was used as a means of addressing this issue. In chronic infection, the dominant HLA-A*0201-restricted CTL response is directed towards the epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This epitope is targeted by 75% of HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive infection. Despite using the highly sensitive peptide-major histocompatibility complex tetramer and intracellular cytokine assays, responses to the SL9 epitope were not detectable in any of 11 HLA-A*0201-positive subjects with acute HIV-1 infection (P = 2 x 10(-6)), even when assays were repeated using the SL9 peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in chronic infection may differ substantially from those that constitute the initial antiviral CTL response. This finding is an important consideration in vaccine design and in the evaluation of vaccine candidates.

Acute Disease↗

Blood genomic responses differ after stroke, seizures, hypoglycemia, and hypoxia: blood genomic fingerprints of disease.

Using microarray technology, we investigated whether the gene expression profile in white blood cells could be used as a fingerprint of different disease states. Adult rats were subjected to ischemic strokes, hemorrhagic strokes, sham surgeries, kainate-induced seizures, hypoxia, or insulin-induced hypoglycemia, and compared with controls. The white blood cell RNA expression patterns were assessed 24 hours later using oligonucleotide microarrays. Results showed that many genes were upregulated or downregulated at least twofold in white blood cells after each experimental condition. Blood genomic response patterns were different for each condition. These results demonstrate the potential of blood gene expression profiling for diagnostic, mechanistic, and therapeutic assessment of a wide variety of disease states.

Animals↗

Influence of environmental salinity on messenger RNA levels of growth hormone, prolactin, and somatolactin in pituitary of the channel catfish (Ictalurus punctatus).

Pituitary growth hormone (GH), prolactin (PRL), and somatolactin (SL) messenger RNA levels in channel catfish (Ictalurus punctatus) were examined under various environmental and physiological conditions. Catfish were sampled following salinity challenge, during the winter (December) and spring or summer (April or July), and at different sizes (15-18 g, 620-664 g, and 956-1134 g). When catfish (956-1134 g) were transferred from freshwater to saline water containing 8 ppt NaCl, their plasma [Na(+)] increased significantly above values in the freshwater control group until they were transferred back to freshwater. Pituitary GH mRNA levels were low for the first 24 hours following transfer to saline water, but thereafter were significantly elevated above control values until the fish were transferred back to freshwater. Pituitary GH mRNA levels were highest in July and lowest in December. Growth hormone mRNA levels were also elevated in the size groups 15-18 g and 956-1134 g in July when compared with December values. Pituitary PRL mRNA levels increased for the first 24 hours following transfer to saline water (956-1134 g), but thereafter were significantly lower than control values until the fish were transferred back to freshwater. Pituitary PRL mRNA levels were highest in April and July and lowest in December, and were also elevated in the size groups 620-664 g and 956-1134 g. Pituitary SL mRNA levels were unaffected in catfish transferred to saline water; however, levels were significantly elevated in catfish of the 956-1134-g size group sampled in April when compared with December. These results suggest the involvement of GH in adaptation to brackish water and of PRL in adaptation to freshwater in the catfish, and seasonal and size-related differences in pituitary GH, PRL, and SL mRNA levels.

Journal Article↗

Hierarchical approach to predicting permeation in ion channels.

A hierarchical computational strategy combining molecular modeling, electrostatics calculations, molecular dynamics, and Brownian dynamics simulations is developed and implemented to compute electrophysiologically measurable properties of the KcsA potassium channel. Models for a series of channels with different pore sizes are developed from the known x-ray structure, using insights into the gating conformational changes as suggested by a variety of published experiments. Information on the pH dependence of the channel gating is incorporated into the calculation of potential profiles for K(+) ions inside the channel, which are then combined with K(+) ion mobilities inside the channel, as computed by molecular dynamics simulations, to provide inputs into Brownian dynamics simulations for computing ion fluxes. The open model structure has a conductance of approximately 110 pS under symmetric 250 mM K(+) conditions, in reasonable agreement with experiments for the largest conducting substate. The dimensions of this channel are consistent with electrophysiologically determined size dependence of quaternary ammonium ion blocking from the intracellular end of this channel as well as with direct structural evidence that tetrabutylammonium ions can enter into the interior cavity of the channel. Realistic values of Ussing flux ratio exponents, distribution of ions within the channel, and shapes of the current-voltage and current-concentration curves are obtained. The Brownian dynamics calculations suggest passage of ions through the selectivity filter proceeds by a "knock-off" mechanism involving three ions, as has been previously inferred from functional and structural studies of barium ion blocking. These results suggest that the present calculations capture the essential nature of K(+) ion permeation in the KcsA channel and provide a proof-of-concept for the integrated microscopic/mesoscopic multitiered approach for predicting ion channel function from structure, which can be applied to other channel structures.

Bacterial Proteins↗

Coumaroyl flavonol glycosides from the leaves of Ginkgo biloba.

Two coumaroyl flavonol glycosides, isorhamnetin 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside], and kaempferol 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside]-7-O-beta-D-glucopyranoside, were isolated from the n-BuOH extract of Ginkgo biloba leaves. These two, together with six other flavonol glycosides, kaempferol 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside], quercetin 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside], quercetin 3-O-alpha-L-[6"'-p-coumaroyl-(beta-D)-glucopyranosyl-(1,2)-rhamnopyranoside]-7-O-beta-D-glucopyranoside, quercetin 3-O-beta-D-glucopyranosyl-(1-2)-alpha-L-rhamnopyranoside, quercetin 3-O-beta-rutinoside, and quercetin 3-O-beta-D-glucopyranoside, showed profound antioxidant activities in DPPH and cytochrome-c reduction assays using the HL-60 cell culture system.

Antioxidants↗

Phosphodiesterase 3B gene expression is enhanced in the liver but reduced in the adipose tissue of obese insulin resistant db/db mouse.

Phosphodiesterase (PDE) 3B, when activated by insulin, causes a decrease in intracellular cAMP concentration. The activation of this enzyme results in the reduced output of free fatty acids (FFA) from adipocytes, and an increased lipogenesis in liver. We have recently shown that PDE3B gene expression is reduced in adipose tissues of KKAy mice. We intend to further elucidate the regulation of PDE3B in liver as well as adipose tissues in relation to the insulin resistant state. We examined PDE3B gene expression in liver and adipose tissues of obese, insulin-resistant diabetic db/db mice and also checked the effect of an insulin-sensitizing drug, troglitazone, on this gene expression. In the liver of db/db mice, PDE3B mRNA, its corresponding protein, and the associated catalytic activity were all increased by 2.1, 1.9 and 1.6-fold, respectively, over those in db/+ control mice. Histological examination revealed substantial triglyceride storage in the liver of db/db mice. Conversely, in the adipose tissue of db/db mice, PDE3B mRNA, protein, and its associated activity were all decreased by 0.38, 0.33 and 0.36-fold, respectively. Troglitazone, which has no effect on PDE3B in liver, increased the expression of this gene in adipocytes. This increase is associated with a reduction in the elevated levels of serum insulin, glucose, FFA and triglycerides. The reduced PDE3B gene expression in adipose tissues, which results in the elevation of serum FFA, could be the primary event in the development of insulin resistance in db/db mice. The enhanced PDE3B gene expression may correlate with changes in triglyceride storage in the liver of these mice.

3',5'-Cyclic-AMP Phosphodiesterases↗

Oestrogen-mediated suppression of tumour necrosis factor alpha-induced apoptosis in MCF-7 cells: subversion of Bcl-2 by anti-oestrogens.

In oestrogen receptor (ER)-positive breast carcinoma cells, 17beta-oestradiol suppresses a dose-dependent induction of cell death by tumour necrosis factor alpha (TNF). The ability of oestrogens to promote cell survival in ER-positive breast carcinoma cells is linked to a coordinate increase in Bcl-2 expression, an effect that is blocked with the pure anti-oestrogen ICI 182,780. The role of Bcl-2 in MCF-7 cell survival was confirmed by stable overexpression of Bcl-2 which resulted in suppression of apoptosis induced by doxorubicin (DOX), paclitaxel (TAX) and TNF as compared to vector-control cells. The pure anti-oestrogen ICI 182,780 in combination with TNF, DOX or TAX potentiated apoptosis in vector-transfected cells. Interestingly, pre-treatment with ICI 182,780 markedly enhanced chemotherapeutic drug- or TNF-induced apoptosis in Bcl-2 expressing cells, an effect that was correlated with ICI 182,780 induced activation of c-Jun N-terminal kinase. Our results suggest that the effects of oestrogens/anti-oestrogens on the regulation of apoptosis may involve coordinate activation of signalling events and Bcl-2 expression.

Antibiotics, Antineoplastic↗

Four new isoflavone triglycosides from Sophora japonica.

Four new isoflavone triglycosides, genistein 7-O-beta-D-glucopyranoside-4'-O-[(alpha-L-rhamnopyranosyl)-(1-->2)-beta-D-glucopyranoside] (1), genistein 7-O-beta-D-glucopyranoside-4'-O-[(beta-D-glucopyranosyl)-(1-->2)-beta-D-glucopyranoside] (2), genistein 7-O-alpha-L-rhamnopyranoside-4'-O-[(alpha-L-rhamnopyranosyl)-(1-->2)-beta-D-glucopyranoside] (3), and genistein 7-O-alpha-L-rhamnopyranoside-4'-O-[(beta-D-glucopyranosyl)-(1-->2)-beta-D-glucopyranoside] (4), together with nine known compounds, namely, genistein 7-O-beta-D-glucopyranoside-4'-O-beta-D-glucopyranoside, sophorabioside, prunetin 4'-O-beta-D-glucopyranoside, sophororicoside, genistin, rutin, kaempferol 3-O-beta-rutinoside, quercetin 3-O-beta-D-glucopyranoside, and kaempferol 3-O-beta-D-glucopyranoside, were isolated from the pericarps of Sophora japonica. The structures of 1-4 were determined by spectroscopic methods.

Carbohydrate Sequence↗