[Treatment of oral leukoplakia with chinese herbs(No.1) and transferrin factor]
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Journal Article↗
Biomedical subjects
H Yang
Publications and source records attributed to H Yang.
Glucose control and long-term survival in biobreeding/Worcester rats after intraperitoneal implantation of hydrophilic macrobeads containing porcine islets without immunosuppression.
BACKGROUND: We investigated the effectiveness of implanted macrobeads containing porcine islets as long-term therapy for type I diabetes mellitus in Biobreeding/Worcester (BB/Wor) rats, an animal model of spontaneous type I human diabetes. End points included acute control of glucose, weight gain, survival time, and the renal changes associated with diabetes. MATERIALS AND METHODS: Eighteen chronic spontaneously diabetic BB/Wor rats were each implanted with 56-150 porcine islet macrobeads secreting 1.3-5.2 U of insulin/24 hr in culture medium at 37 degrees C. Their clinical courses and selective histological observations were compared with those of animals maintained on Linplant insulin-release implants (6 rats) or protamine zinc insulin alone (10 rats). RESULTS: The rats that underwent porcine islet macrobead implantation (PIMI) survived for a mean of 171 days (range, 79-288) after implantation without exogenous insulin, immunosuppressive treatment, or lactated Ringer's therapy. All appeared healthy and maintained their body weights (mean 356+/-21 g) throughout this period, even though their nonfasting blood glucose levels fluctuated significantly, with the mean for the group being 245+/-102 mg/dl (range, 157-320 mg/dl). There was mild glucosuria in some animals. In comparison, the 10 BB/Wor rats maintained on exogenous protamine zinc insulin had a mean survival time of 53 days (range, 10-217), a "last entry" mean body weight of 283+/-23 g, and a mean nonfasting glucose level of 340+/-90 mg/dl. The six Linplant implant animals had a mean survival time of 164 days (range, 1-264 days), a "last entry" mean body weight of 374+/-21 g, and a mean nonfasting glucose level of 189+/-91 mg/dl (range, 135-219). Episodes of ketonuria, abrupt loss of body weight, dehydration, and symptomatic hypoglycemia were more common in both these groups than in the PIMI animals. Glucose tolerance tests comparing diabetic animals treated with porcine islet macrobead implants, exogenous insulin-treated diabetic BB/Wor rats, and normal nondiabetic Wistar-Furth rats showed that the responses of those with the macrobead implants were similar to those of the normal rats, while the exogenous insulin-treated diabetic BB/Wor rats had the expected abnormal responses. Light microscopic examination of the PIMI and Linplant animals' kidney sections appeared normal, whereas those of the exogenous insulin-injected BB rats showed moderate focal tubular atrophy and an increased mesangial matrix. Macrobeads retrieved from the peritoneal cavity at necropsy were found to secrete insulin, C-peptide, and glucagon, indicating that they were still functional after 199 or more days in the peritoneal cavity. CONCLUSIONS: Our results indicate that macrobeads containing porcine islets implanted intraperitoneally in natural insulin-dependent diabetic BB/Wor rats are capable of normalizing glucose control, permitting a normal life span, and preventing the renal changes normally associated with diabetes. Therefore, further short- and long-term studies of porcine islet macrobead implantation in chemically induced and naturally occurring diabetes in rodents, as well as larger animals including dogs, monkeys and possibly humans, are merited.
Animals↗
Hyperthyroidism decreases thyrotropin-releasing hormone gene expression in the caudal raphe nuclei and the parapyramidal regions in rats.
Altered thyroid statuses are associated with autonomic disorders. Medullary thyrotropin-releasing hormone (TRH) and substance P (SP) regulate autonomic nervous activity. The influences of thyroid statuses on TRH and SP gene expressions in the caudal raphe nuclei and the parapyramidal regions were studied using quantitative in situ hybridization histochemistry. In male rats thyroidectomized (Tx) for 30 days, the serum T4 levels decreased by 64% and the medullary pro-TRH mRNA signals (silver grains per neuron) significantly increased by 32-45%. These changes were prevented by daily i.p. T4 (2 microg/100 g) injection in Tx rats. In sham operated/T4 (20 microg/100 g, daily) injected rats, T4 levels significantly increased by 88% and the silver grains decreased by 38-40%. Medullary SP mRNA signals were not significantly changed by altering thyroid status. These results support the concept that thyroid hormone regulates medullary TRH gene expression by negative feedback.
Animals↗
Permanent cardiovascular protection from hypertension by the AT(1) receptor antisense gene therapy in hypertensive rat offspring.
Our previous studies have demonstrated that the introduction of angiotensin II type I receptor antisense (AT(1)R-AS) cDNA by a retrovirally mediated delivery system prevents the development of hypertension in the spontaneously hypertensive rat (SHR), an animal model for primary hypertension in humans. These results have led us to propose the hypothesis that an interruption of the renin-angiotensin system (RAS) activity at a genetic level would prevent hypertension on a permanent basis. F(1) and F(2) generations of offspring from a retroviral vector, LNSV- and LNSV-AT(1)R-AS-treated SHR, were generated, and various physiological parameters indicative of hypertension were studied and compared with those of their parents to investigate this hypothesis. Both F(1) and F(2) generations of LNSV-AT(1)R-AS-treated SHR expressed a persistently lower blood pressure, decreased cardiac hypertrophy and fibrosis, decreased medial thickness, and normalization of renal artery excitation-contraction coupling, Ca(2+) current, and [Ca(2+)](i) when compared with offspring derived from the LNSV-treated SHR. In fact, the magnitude of the prevention of these pathophysiological alterations was similar to that observed in the LNSV-AT(1)R-AS-treated SHR parent. The prevention of cardiovascular pathophysiology and expression of normotensive phenotypes are, at least in part, a result of integration and subsequent transmission of AT(1)R-AS from the SHR parents to offspring. These data demonstrate that a single intracardiac injection of LNSV-AT(1)R-AS causes a permanent cardiovascular protection against hypertension as a result of a genomic integration and germ line transmission of the AT(1)R-AS in the SHR offspring.
Animals↗
Oryza sativa PSK gene encodes a precursor of phytosulfokine-alpha, a sulfated peptide growth factor found in plants.
Phytosulfokine-alpha [PSK-alpha, Tyr(SO(3)H)-Ile-Tyr(SO(3)H)-Thr-Gln], a sulfated mitogenic peptide found in plants, strongly promotes proliferation of plant cells in culture at very low concentrations. Oryza sativa PSK (OsPSK) cDNA encoding a PSK-alpha precursor has been isolated. The cDNA is 725 base pairs long, and the 89-aa product, preprophytosulfokine, has a 22-aa hydrophobic region that resembles a cleavable leader peptide at its NH(2) terminus. The PSK-alpha sequence occurs only once within the precursor, close to the COOH terminus. [Ser(4)]PSK-alpha was secreted by transgenic rice Oc cells harboring a mutated OsPSK cDNA, suggesting proteolytic processing from the larger precursor, a feature commonly found in animal systems. Whereas PSK-alpha in conditioned medium with sense transgenic Oc cells was 1.6 times as concentrated as in the control case, antisense transgenic Oc cells produced less than 60% of the control level. Preprophytosulfokine mRNA was detected at an elevated constitutive level in rice Oc culture cells on RNA blot analysis. Although PSK-alpha molecules have never been identified in any intact plant, reverse transcription-PCR analysis demonstrated that OsPSK is expressed in rice seedlings, indicating that PSK-alpha may be important for plant cell proliferation both in vitro and in vivo. DNA blot analysis demonstrated that OsPSK homologs may occur in dicot as well as monocot plants.
Amino Acid Sequence↗
Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
The PTEN tumor suppressor is mutated in diverse human cancers and in hereditary cancer predisposition syndromes. PTEN is a phosphatase that can act on both polypeptide and phosphoinositide substrates in vitro. The PTEN structure reveals a phosphatase domain that is similar to protein phosphatases but has an enlarged active site important for the accommodation of the phosphoinositide substrate. The structure also reveals that PTEN has a C2 domain. The PTEN C2 domain binds phospholipid membranes in vitro, and mutation of basic residues that could mediate this reduces PTEN's membrane affinity and its ability to suppress the growth of glioblastoma tumor cells. The phosphatase and C2 domains associate across an extensive interface, suggesting that the C2 domain may serve to productively position the catalytic domain on the membrane.
Amino Acid Sequence↗
Production of human alloreactive antibodies by uremic sensitized lymphocytes engrafted in severe combined immunodeficient mice.
BACKGROUND: Numerous studies have documented antibody responses to nominal antigens in human peripheral blood lymphocyte (hu-PBL)-severe combined immunodeficient (SCID) mice engrafted with PBL. We suggest, therefore, that engraftment of SCID mice by allosensitized cells produces alloreactive antibodies (allo-Ab). As such, SCID mice can be used as a model to examine the cellular basis of the sustenance of humoral alloresponses. METHODS: C.B-17 SCID mice were engrafted intraperitoneally with PBL from sensitized uremic patients for 5 weeks and classified into the following: group 1, 8 mice engrafted with unactivated cells (n = 5; n = sensitized patients); group 2, 6 mice engrafted with unactivated PBL (n = 3) followed 2 days later by in vivo activation with interleukin-2 (IL-2) and lipopolysaccharide (LPS); group 3, 11 mice engrafted with cells preactivated in vitro with IL-2 and LPS (n = 6); group 4, 9 mice engrafted with cells preactivated with irradiated allogeneic transformed B cells, IL-2, and LPS (n = 5); group 5, 10 mice engrafted with cells preactivated with IL-2, LPS, and HLA class II allopeptides and adjuvant (n = 6); group 6, 8 control mice engrafted with control cells preactivated with IL-2 and LPS. Two weeks later, each group was rechallenged by the same stimuli. Allo-Ab production was measured by the panel-reactive antibody PRA-STAT ELISA method. Results. Allo-Ab was produced in 54.5% of group 3, 43% of group 4; 80% of group 5, and 0% of groups 1, 2, and 6. The ratio of alloreactive positive wells in the allo-Ab-producing PBL-hu-SCID mice to that present in the respective patient's sera was 82%, 52%, and 87% in groups 3, 4, and 5, respectively. Conclusions. The study demonstrates the feasibility of using the hu-PBL-SCID model to study alloreactive memory B-cell function in humans. Discrete HLA-class allopeptides (group 5) appeared more potent allo-Ab producers than allogeneic cells (group 4).
Adjuvants, Immunologic↗
An integrated decoupler for capillary electrophoresis with electrochemical detection: application to analysis of brain microdialysate.
An approach to capillary electrophoresis with electrochemical detection (CE-EC) suitable for determination of dopamine in 1-min brain microdialysate samples is described. The CE-EC system includes an electrochemical detection cell that permits easy, precise, and permanent alignment of a carbon fiber microelectrode with a separation capillary (30-micron i.d., 75-cm length). Amperometric detection was performed at a constant applied potential of 600 mV with respect to a Ag/AgCl reference electrode. Decoupling of the electrophoretic current from the amperometric detector was accomplished with an integrated end-column decoupler prepared by etching the capillary outlet with HF. The decoupler produces baseline noise of 50 fA, or less, in the presence of 10-20-muA current in the separation capillary. The low baseline noise affords low mass (attomoles) and low concentration (nanomolar) detection limits for dopamine and 4-methylcatechol. A peak attributable to dopamine was identified in electropherograms of brain microdialysate samples obtained from anesthetized rats. Identification of the dopamine peak was confirmed by pharmacological methods. Dopamine was readily detected in 1-min brain microdialysate samples. The dopamine concentration in 1-min brain microdialysis samples was significantly altered by drug treatments and by brief electrical stimulation of dopaminergic axons.
Animals↗
Isolation of high-affinity peptide antagonists of 14-3-3 proteins by phage display.
The 14-3-3 proteins interact with diverse cellular molecules involved in various signal transduction pathways controlling cell proliferation, transformation, and apoptosis. To aid our investigation of the biological function of 14-3-3 proteins, we have set out to identify high-affinity antagonists. By screening phage display libraries, we have identified a set of peptides which bind 14-3-3 proteins. One of these peptides, termed R18, exhibited a high affinity for different isoforms of 14-3-3 with estimated K(D) values of 7-9 x 10(-)(8) M. Recognition of multiple isoforms of 14-3-3 suggests the targeting of R18 to a structure that is common among 14-3-3 proteins, such as the conserved ligand-binding groove. Indeed, mutations that alter critical residues in the ligand-binding site of 14-3-3 drastically decreased the level of 14-3-3-R18 association. R18 efficiently blocked the binding of 14-3-3 to the kinase Raf-1, a physiological ligand of 14-3-3, and effectively abolished the protective role of 14-3-3 against phosphatase-induced inactivation of Raf-1. The cocrystal structure of R18 in complex with 14-3-3zeta revealed the occupancy of the general binding groove of 14-3-3zeta by R18, explaining the potent inhibitory effect of R18 on 14-3-3-ligand interactions. Such a well-defined peptide will be an effective tool for probing the role of 14-3-3 in various signaling pathways, and may lead to the development of 14-3-3 antagonists with pharmacological applications.
14-3-3 Proteins↗
Effect of thioacetamide on the hepatic expression of gamma-glutamylcysteine synthetase subunits in the Rat.
Glutathione (GSH) is the main nonprotein thiol important in antioxidant defense and maintenance of the intracellular redox state. A major determinant of the rate of GSH synthesis is the activity of the rate-limiting enzyme, gamma-glutamylcysteine synthetase (GCS). A heavy (HS) and light subunit (LS) make up GCS; oxidative stress regulates both transcriptionally. cis-Acting elements important for the oxidative stress-induced transcriptional up-regulation of both subunits are antioxidant response element (ARE) and activator protein-1 (AP-1) site. The nuclear factor-kappaB (NF-kappaB) binding site may also regulate the heavy subunit. Increased GSH and gamma-glutamyltranspeptidase are often observed in preneoplastic hepatocyte nodules and may be important in hepatocarcinogenesis. The current work examined the effect of a commonly used hepatocarcinogen, thioacetamide (TAA), on the expression of GCS subunits. After 3 weeks of TAA treatment, liver GSH level remained unchanged despite significant oxidative stress as measured by the thiobarbituric acid reactive substance assay. The mRNA levels of GCS-HS and GCS-LS increased six- and fourfold, respectively, and the protein level of GCS-HS and GCS activity all increased. Electrophorectic mobility shift assay showed binding to ARE, AP-1, and NF-kappaB probes all increased. These results suggest TAA treatment increased hepatic GCS subunit expression and GCS activity by inducing oxidative stress and increasing the binding to redox-sensitive cis-acting elements important for transcriptional up-regulation of GCS. This is the first in vivo study that examined the effect of a hepatocarcinogen on GCS expression.
Animals↗
Rapid, direct determination of polyphenols in tea by reversed-phase column liquid chromatography.
Column liquid chromatography on a C18-bonded silica column with water-methanol-acetic acid as eluent was used to determine polyphenols and caffeine in tea. Without any pretreatment, catechin, epicatechin gallate, epigallocatechin gallate, epigallocatechin, epicatechin and caffeine were separated successfully within 15 min. The detection limits (S/N = 3) of polyphenols studied were 1.8-24 mg/l at a detection wavelength 270 nm. The linear range of the peak area calibration curves for the analytes were over two orders of magnitude with a correlation coefficient of 0.996-0.999. Using this method, some Chinese tea samples were analyzed with a good reproducibility (RSD are below 5%).
Caffeine↗
Glypican-3-deficient mice exhibit developmental overgrowth and some of the abnormalities typical of Simpson-Golabi-Behmel syndrome.
Glypicans are a family of heparan sulfate proteoglycans that are linked to the cell surface through a glycosyl-phosphatidylinositol anchor. One member of this family, glypican-3 (Gpc3), is mutated in patients with the Simpson-Golabi-Behmel syndrome (SGBS). These patients display pre- and postnatal overgrowth, and a varying range of dysmorphisms. The clinical features of SGBS are very similar to the more extensively studied Beckwith-Wiedemann syndrome (BWS). Since BWS has been associated with biallelic expression of insulin-like growth factor II (IGF-II), it has been proposed that GPC3 is a negative regulator of IGF-II. However, there is still no biochemical evidence indicating that GPC3 plays such a role.Here, we report that GPC3-deficient mice exhibit several of the clinical features observed in SGBS patients, including developmental overgrowth, perinatal death, cystic and dyplastic kidneys, and abnormal lung development. A proportion of the mutant mice also display mandibular hypoplasia and an imperforate vagina. In the particular case of the kidney, we demonstrate that there is an early and persistent developmental abnormality of the ureteric bud/collecting system due to increased proliferation of cells in this tissue element. The degree of developmental overgrowth of the GPC3-deficient mice is similar to that of mice deficient in IGF receptor type 2 (IGF2R), a well characterized negative regulator of IGF-II. Unlike the IGF2R-deficient mice, however, the levels of IGF-II in GPC3 knockouts are similar to those of the normal littermates.
Abnormalities, Multiple↗
HMG-1 as a late mediator of endotoxin lethality in mice.
Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
Animals↗
Magnetite Nanoparticles Prepared by Precipitation from Partially Reduced Ferric Chloride Aqueous Solutions.
Spherical magnetite particles with mean diameter of about 10 nm or less were prepared by means of a reduction-precipitation method with ferric chloride as starting material, which was partially reduced to ferrous salts by Na2SO3 before alkalinizing with ammonia. It was found that the nature of the product depends strongly on the initial ratio R0 = [Fe3+]0/[SO2-3]0. The most appropriate ratio was 3 as proved by X-ray diffraction analysis on the samples although the initial concentration of ferric chloride can be different. Particle diameter increased from ca. 3 to ca. 11 nm with an increase of the concentration of aqueous ferric chloride from 0.075 to 0.45 mol dm-3. The advantage of this method lies in the formation of a red intermediate during the reduction process, which enables us to prevent the reoxidation of the ferrous ions by adding precipitation agents at the end of the reduction reaction without the protection of nitrogen or argon. Copyright 1999 Academic Press.
Journal Article↗
Rap1 GTPase-activating protein SPA-1 negatively regulates cell adhesion.
Rap1 GTPase is activated by a variety of stimulations in many types of cells, but its exact functions remain unknown. In this study we have shown that SPA-1 interferes with Rap1 activation by membrane-targeted C3G, C3G-F, in 293T cells through the GTPase activating protein (GAP) activity. SPA-1 transiently expressed in HeLa cells was mostly localized at the cortical cytoskeleton and induced rounding up of the cells, whereas C3G-F conversely induced extensive cell spreading. Conditional SPA-1 overexpression in HeLa cells by tetracycline-regulative system suppressed Rap1 activation upon plating on dishes coated with fibronectin and resulted in the reduced adhesion. When SPA-1 was conditionally induced after the established cell adhesion, the cells gradually rounded up and detached from the dish. Both effects were counteracted by exogenous fibronectin in a dose-dependent manner. Retroviral overexpression of SPA-1 in promyelocytic 32D cells also inhibited both activation of Rap1 and induction of cell adhesion by granulocyte colony stimulating factor without affecting differentiation. These results have indicated that Rap1 GTP is required for the cell adhesion induced by both extracellular matrix and soluble factors, which is negatively regulated by SPA-1.
Animals↗
Kainic acid into the parapyramidal region protects against gastric injury by ethanol.
Neurons in the parapyramidal region of the ventral medulla project to the dorsal vagal complex and intermediolateral column. Kainic acid (0.5-5.0 ng) microinjected unilaterally into the parapyramidal region reduced 45% ethanol-induced gastric lesions by 50-60% in urethane anesthetized rats. Microinjections at sites nearby, but outside of the parapyramidal region, had no effect. These results provide the first evidence that the activation of parapyramidal region neurons influences gastric function and suggests a possible role of this ventral medulla region in gastric regulation.
Analysis of Variance↗
Vicia root-micronuclei assays on the clastogenicity of water samples from the Kui River near Xuzhou city, People's Republic of China.
The Vicia root-micronucleus (VR-MCN) bioassay was used to determine the genotoxicity of water samples collected from the Kui River near Xuzhou city, China. Results show that all water samples induced elevated MCN frequencies over background. This indicates that the river water was polluted with genotoxic material. The source of pollutants in this river is discussed.
China↗
Localization of a human nucleoporin 155 gene (NUP155) to the 5p13 region and cloning of its cDNA.
Nucleoporins are the main components of nuclear pore complexes (NPCs) involved in nucleo-cytoplasmic transport. Starting with an expressed DNA fragment retrieved by exon trapping from pooled human BAC clones mapped to the short arm of chromosome 5, we identified a human nucleoporin cDNA sequence by PCR from a human testis cDNA library. The coding sequence showed high homology to that of the rat nucleoporin 155 (Nup155) cDNA. FISH analysis with the human BAC clone as probe localized the human NUP155 gene to chromosome band 5p13. Northern analysis showed that the human NUP155 gene was expressed at different levels in all tissues tested. Two species of transcripts were observed with estimated lengths of 5.4 and 4.7 kb, respectively, in concordance with the finding of two alternative polyadenylation sites in the cDNA. The genomic location of the human NUP155 gene suggests a possible role in the mental and developmental retardation associated with hemizygous deletions of the 5p13 region.
Amino Acid Sequence↗