Biomedical subjects

X M Yang

Publications and source records attributed to X M Yang.

At least 37 records · Page 2Linked to original sources

PubMed2000

Ability of insulin to modulate hepatic glucose production in aging rats is impaired by fat accumulation.

Increased total fat mass (FM) and visceral fat (VF) may account in part for age-associated decrease in hepatic insulin action. This study determined whether preventing the changes in body fat distribution abolished this defect throughout aging. We studied the F(1) hybrid of Brown Norway-Fischer 344 rats (n = 29), which we assigned to caloric restriction (CR) or fed ad libitum (AL). CR (55% of the calories consumed by AL) was initiated and used at 2 mo to prevent age-dependent increases in FM and VF. AL rats were studied at 2, 8, and 20 mo; CR rats were studied at 8 and 20 mo. VF and FM remained unchanged throughout aging in CR rats. AL-fed rats at 8 and 20 mo had over fourfold higher FM and VF compared with both CR groups. Insulin clamp studies (3 mU. kg(-1). min(-1) with somatostatin) were performed to assess hepatic insulin sensitivity. Prevention of fat accretion resulted in a marked improvement in insulin action in the suppression of hepatic glucose production (HGP) (6.3 +/- 0.3 and 7.2 +/- 1.2 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 8.3 +/- 0.5 and 10.8 +/- 0.9 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The rate of gluconeogenesis (by enrichment of hepatic uridine diphosphate glucose and phosphoenolpyruvate pools by [(14)C]lactate) was unchanged in all groups. The improvement in hepatic insulin action in the CR group was mostly due to effective suppression of glycogenolysis (4.4 +/- 0.3 and 4.9 +/- 0.3 mg. kg(-1). min(-1) in 8- and 20-mo CR rats vs. 5.8 +/- 0.6 and 8.2 +/- 1.0 mg. kg(-1). min(-1) in 8- and 20-mo AL rats, respectively). The results demonstrated the preservation of hepatic insulin action in aging CR rats. Therefore, body fat and its distribution are major determinants of age-associated hepatic insulin resistance.

Adipose Tissue↗

PubMed2000

Aging does not contribute to the decline in insulin action on storage of muscle glycogen in rats.

Increase in fat mass (FM) and changes in body composition may account for the age-associated impairment in insulin action on muscle glycogen storage. We wish to examine whether preventing the increase in FM abolishes this defect seen with aging. We studied the novel aging model of F1 hybrids of BN/F344 NIA rats fed ad libitum (AL) at 2 (weighing 259+/-17 g), 8 (459+/-17 g), and 20 (492+/-10 g) mo old. To prevent the age-dependent growth in FM, rats were caloric restricted (CR) at 2 mo by decreasing their daily caloric intake by 45% (weighing 292+/-5 g at 8 mo, 294+/-9 g at 20 mo). As designed, the lean body mass (LBM) and %FM remained unchanged through aging (8 and 20 mo old) in the CR rats and was similar to that of 2-mo-old AL rats. However, 8- and 20-mo-old AL-fed rats had three- to fourfold higher FM than both CR groups. Peripheral insulin action at physiological hyperinsulinemia was determined (by 3 mU x kg(-1). min(-1) insulin clamp). Prevention of fat accretion maintained glucose uptake (R(d); 29+/-2, 29+/-2, and 31+/-4 mg x kg LBM(-1) x min(-1)) and glycogen synthesis rates (GS, 12+/-1, 12 +/-1, and 14+/-2 mg x kg LBM(-1) x min(-1)) at youthful levels (2 mo AL) in 8- and 20-mo-old CR rats, respectively. These levels were significantly increased (P<0.001) compared with AL rats with higher %FM (R(d), 22+/-1 and 22+/-2 and GS, 7+/-1 and 8+/-2 mg x kg LBM(-1). min(-1) in 8- and 20-mo-old rats, respectively). The increase in whole body GS in age-matched CR rats was accompanied by approximately 40% increased accumulation of [(3)H] glucose into glycogen and a similar increase in insulin-induced muscle glycogen content. Furthermore, the activation of glycogen synthase increased, i.e., approximately 50% decrease in the Michaelis constant, in both CR groups (P<0.01). We conclude that chronic CR designed to prevent an increase in storage of energy in fat maintained peripheral insulin action at youthful levels, and aging per se does not result in a defect on the pathway of glycogen storage in skeletal muscle.

Aging↗

PubMed2000

[Protective effects of gangliosides on cerebral neuronal damage of rat during acute hypoxia].

OBJECTIVE: To observe the preventive and therapeutic effects of gangliosides on acute altitude hypoxic brain damage. METHOD: Fifteen Wistar rats, weighed 180-220 g, were randomly divided into 3 groups, hypoxia group A, hypoxia group B and normoxia group. The rats in hypoxia group A were exposed to a simulated altitude of 7000 m for 5 hours and the rats in hypoxia group B were exposed to hypoxia after intraperitoneal administration of mixed gangliosides (100 mg/kg/d) for 3 days. RESULT: Gangliosides could ameliorate the severity of damage in neuronal bodies, cellular skeletons and synapses, especially in synapses. CONCLUSION: It is suggested that gangliosides are effective in preventing and treating hypoxic brain damages by decreasing the accumulation of intracellular Ca2+, and stabilizing CaM and CaM PKII activity during acute hypoxia.

Altitude Sickness↗

PubMed2000

[Isolation of regulation genes related with liver regeneration by representational difference analysis].

mRNA isolated from 2/3 partially hepatectomied rats was used as a tester for representational difference analysis (RDA). The subtracted tester cDNA was cloned into a T vector and a rat regeneration liver specific EST pool was constructed, which contained about 30000 independent clones. A sequence analysis of 52 clones randomly picked up from this pool indicated that the liver regeneration specific sequences were enriched, and the results of RNA blots revealed some novel genes in association with liver regeneration.

Animals↗

PubMed2000

[The effect of chronic ototoxicity of gentamicin on the function of auditory efferents].

OBJECTIVE: To study the effect of chronic ototoxicity of gentamicin on the function of the cochlea and auditory efferents. METHOD: The effect of chronic ototoxicity of gentamicin on the function of the cochlea was determined by recording thresholds of the compound action potentials (CAP) of the auditory nerves to tone pip at 4, 6, 8, 10 and 12 kHz. The function of the medial olivocochlear (MOC) system was determined, through the observation of the effect of the contralateral noise (CLN) on CAP, before and after gentamicin administration. RESULT: The suppression effects of CLN on CAP were irreversibly eliminated, and the effects were most obvious at the 11th week after gentamicin (P < 0.01), and the response threshold of CAP was raised about 10 dB and 25 dB, respectively, at the 3rd and 11th week after the application of gentamicin. These results were most related to the morphological changes on cochlear efferents and hair cells. CONCLUSION: The auditory efferents play an important role in the chronic ototoxicity of gentamicin.

Animals↗

PubMed2000

[Benign paroxysmal positional vertigo following radiotherapy for nasopharyngeal carcinoma (report of 3 cases)].

OBJECTIVE: To investigate the effect of ionizing radiation on the vestibule of the inner ear. METHOD: Three patients with benign paroxysmal positional vertigo (BPPV) accompanied by hearing loss following radiotherapy for nasopharyngeal carcinoma (NPC) were reported. Particle repositioning maneuver (PRM) was used as treatment for BPPV, and salvia miltiorrhiza tablets were taken orally to treat hearing loss. RESULT: Two of three cases with BPPV recovered and one was effective; Mean phone frequency hearing increased 10 dB compared with that before therapy. CONCLUSION: Occurrence of BPPV in this series may be related to radiation damage on the vestibule; PRM is a effective modality for the patients with BPPV.

Adult↗

PubMed1999

Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3'-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage.

Mammalian polynucleotide kinases catalyze the 5'-phosphorylation of nucleic acids and can have associated 3'-phosphatase activity, predictive of an important function in DNA repair following ionizing radiation or oxidative damage. The sequences of three tryptic peptides from a bovine 60-kDa polypeptide that correlated with 5'-DNA kinase and 3'-phosphatase activities identified human and murine dbEST clones. The 57.1-kDa conceptual translation product of this gene, polynucleotide kinase 3'-phosphatase (PNKP), contained a putative ATP binding site and a potential 3'-phosphatase domain with similarity to L-2-haloacid dehalogenases. BLAST searches identified possible homologs in Caenorhabditis elegans, Schizosaccharomyces pombe, and Drosophila melanogaster. The gene was localized to chromosome 19q13.3-13.4. Northern analysis indicated a 2-kilobase mRNA in eight human tissues. A glutathione S-transferase-PNKP fusion protein displayed 5'-DNA kinase and 3'-phosphatase activities. PNKP is the first gene for a DNA-specific kinase from any organism. PNKP expression partially rescued the sensitivity to oxidative damaging agents of the Escherichia coli DNA repair-deficient xth nfo double mutant. PNKP gene function restored termini suitable for DNA polymerase, consistent with in vivo removal of 3'-phosphate groups, facilitating DNA repair.

Amino Acid Sequence↗

PubMed1999

Recognition between disordered polypeptide chains from cleavage of an alpha/beta domain: self-versus non-self-association.

Advances in structural biology have provoked a re-evaluation of the biological significance of the disordered state of proteins. We believe that the rules that govern structure, stability and kinetics in the molecular recognition between disordered polypeptide chains can be elucidated by studying processes that couple association with folding. The reassembly of single domain proteins by fragment complementation provides an excellent opportunity to study them. Since almost the complete sequence is available, although not on a single chain, most of the complementary fragments are expected to reassemble. However, that happens not to be the case. We have chosen E. coli thioredoxin (Trx), a small, single alpha/beta-domain protein, as a model system to study the effect of the site and number of cleavages on the reassembly of complementary fragments. We have shown at atomic detail the reassembly after cleavage of a loop (1-73, 74-108) and after cleavage of an alpha-helix (1-37, 38-108). Although both sets of fragments produce native-like complexes, there are clear differences in the interface geometry, apparent stability of the folded state and mechanism of association/folding: (i) the apparent equilibrium dissociation constant for 1-37/38-108 complex (4 microM) is higher than the one for 1-73/74-108 complex (49 nM), (ii) the apparent rate constants of non-self-association are similar (about 10(3) M-1s-1), and (iii) only the 1-37 fragment self-associates under these experimental conditions. Here the competition between self- and non-self-association leads to an apparently less stable 1-37/38-108 complex.

Binding Sites↗

PubMed1999

Smaller infarct after preconditioning does not predict extent of early functional improvement of reperfused heart.

We evaluated the ability of ischemic preconditioning to restore function to salvaged myocardium in rabbits. Although ischemic preconditioning reduces infarct size, few investigators studying recovery of function after coronary occlusions lasting >/=30 min have reported any mechanical benefit in preconditioned hearts. However, because myocardial function was seldom evaluated beyond 5 h after reperfusion stunning may have masked the benefit. Accordingly, rabbits were chronically instrumented with a pneumatic occluder around a branch of the left coronary artery, a pair of 1-mm ultrasonic crystals in the myocardial territory destined to become ischemic, and electrocardiogram (ECG) leads. One week after surgery the ECG and segment length tracing were recorded at rest, during 30-min occlusion and 1 h of reflow, and again at 24, 48, and 72 h. In ischemically preconditioned rabbits, 5-min coronary occlusion and 10-min reperfusion preceded the long occlusion. The beginning and end of systole were determined by recording the first and second heart sounds with a hand-held precordial microphone. Postmortem infarct size was measured with triphenyltetrazolium chloride. During the 30-min coronary occlusion all segments became nearly akinetic or bulged during systole. After 60 min of reflow there was little return of function in either group. Between 24 and 72 h there was minimal recovery in the control group (segment shortening equals 13.3 +/- 4.1% of baseline), whereas function was much better in preconditioned hearts (44.2 +/- 7.4% of baseline, P < 0.02). Infarct size as a percentage of risk zone was much smaller in preconditioned hearts (10.2 +/- 1.4 vs. 29.7 +/- 1.8%, P < 0.001). Thus there is a gradual recovery of systolic function of reperfused myocardium after a coronary occlusion. Although early mechanical recovery is significantly better after preconditioning, it is much less than would be predicted by the reduction of infarct size.

Animals↗

PubMed1999

S-T segment voltage during sequential coronary occlusions is an unreliable marker of preconditioning.

During coronary angioplasty, a stair-step decrease in peak S-T segment elevation from the first to the second coronary occlusion has been assumed to indicate a preconditioning (PC) effect. This association was evaluated with myocardial electrograms in rabbits, which revealed that two sequential 5-min coronary occlusions resulted in a marked decrease in the area under the S-T segment voltage-time curve (P < 0.05) with no change during a third occlusion. Pretreatment with either 5-hydroxydecanoate, a mitochondrial ATP-sensitive potassium (K(ATP)) channel blocker, or anisomycin, an activator of stress-activated protein kinases, had no effect on the stair-step decline in the S-T segment voltage between the first two occlusions. HMR-1883, a potent closer of sarcolemmal K(ATP) channels, abolished changes in S-T segment elevation after brief coronary occlusions but had no effect on the infarct-sparing property of the two preconditioning 5-min occlusions. Interestingly, HMR-1883 blocked myocardial protection from diazoxide, raising doubt that the latter opens only mitochondrial channels. Therefore, myocardial protection and S-T segment changes during ischemia are dissociated. These data suggest that it is the mitochondrial K(ATP) channel that protects the myocardium, and it is the sarcolemmal channel that is responsible for changes in S-T elevation. Therefore, it cannot always be inferred that changes in S-T segment elevation reflect the state of myocardial protection.

Adenosine Triphosphate↗

PubMed1999

Comparison of iodixanol 270 with iohexol 300 in infrapopliteal arteriography. Digital densitometric analysis of angiographic opacification.

PURPOSE: To compare iodixanol 270 mg I/ml with iohexol 300 mg I/ml in infrapopliteal arteriography by measuring digital densitometric vessel opacification and by visually assessing angiographic enhancement. MATERIAL AND METHODS: In a double-blind, dual-balanced, 4-sequence cross-over design, 50 claudicant patients received two contrast media injections (10 min interval) in the superficial femoral artery. Digital angiography was performed at 8 frames/s and time-density curves with a circular region of interest over a distal calf artery were generated. A mixed, linear model was used to identify effects influencing the density measurements. Subjective evaluation of the image quality was made independently by two observers. RESULTS: No statistically significant difference between the contrast media was revealed in the analysis of the densitometric measurements (p=0.14) nor in the subjective visual evaluation (p=0.74). However, the mean density at the time of maximum opacification was higher after the first injection than that after the second injection (p=0.02). There was a tendency towards lower intensity of warmth during injection of iodixanol 270 than during injection of iohexol 300. CONCLUSION: In patients with severe occlusive atherosclerotic disease, iodixanol yielded the same image quality as iohexol in infrapopliteal arteriography, in spite of the 30 mg I/ml lower iodine concentration.

Absorptiometry, Photon↗

PubMed1999

[Biological activity of recombinant human hepatopoietin].

We examined the effects of rhHPO on the cell growth and DNA synthesis of both rat primarily cultured hepatocytes and hepatic carcinoma cell line in vitro by MTS and 3H-TdR in corporation methods. It was indicated that rhHPO is an important stimulating factor of regeneration, which may be developed as a potential drug for the treatment of severe hepatic diseases. We also found an inhibitory effect of rhHPO on the DNA synthesis of lung cancer cell lines GLC-82 in vitro, which might provide a valuable indicator for the study of its specificity and mechanisms.

Animals↗

PubMed1998

Autocrine hepatocyte growth factor provides a local mechanism for promoting axonal growth.

In this report, we describe a novel local mechanism necessary for optimal axonal growth that involves hepatocyte growth factor (HGF). Sympathetic neurons of the superior cervical ganglion coexpress bioactive HGF and its receptor, the Met tyrosine kinase, both in vivo and in vitro. Exogenous HGF selectively promotes the growth but not survival of cultured sympathetic neurons; the magnitude of this growth effect is similar to that observed with exogenous NGF. Conversely, HGF antibodies that inhibit endogenous HGF decrease sympathetic neuron growth but have no effect on survival. This autocrine HGF is required locally by sympathetic axons for optimal growth, as demonstrated using compartmented cultures. Thus, autocrine HGF provides a local, intrinsic mechanism for promoting neuronal growth without affecting survival, a role that may be essential during developmental axogenesis or after neuronal injury.

Animals↗

PubMed1998

The 2 micrometer plasmid stability system: analyses of the interactions among plasmid- and host-encoded components.

The stable inheritance of the 2 micrometer plasmid in a growing population of Saccharomyces cerevisiae is dependent on two plasmid-encoded proteins (Rep1p and Rep2p), together with the cis-acting locus REP3 (STB). In this study we demonstrate that short carboxy-terminal deletions of Rep1p and Rep2p severely diminish their normal capacity to localize to the yeast nucleus. The nuclear targeting, as well as their functional role in plasmid partitioning, can be restored by the addition of a nuclear localization sequence to the amino or the carboxy terminus of the shortened Rep proteins. Analyses of deletion derivatives of the Rep proteins by using the in vivo dihybrid genetic test in yeast, as well as by glutathione S-transferase fusion trapping assays in vitro demonstrate that the amino-terminal portion of Rep1p (ca. 150 amino acids long) is responsible for its interactions with Rep2p. In a monohybrid in vivo assay, we have identified Rep1p, Rep2p, and a host-encoded protein, Shf1p, as being capable of interacting with the STB locus. The Shf1 protein expressed in Escherichia coli can bind with high specificity to the STB sequence in vitro. In a yeast strain deleted for the SHF1 locus, a 2 micrometer circle-derived plasmid shows relatively poor stability.

Activating Transcription Factors↗

PubMed1998

Development of Bacillus thuringiensis fermentation and process control from a practical perspective.

Bacillus thuringiensis (Bt) is the most widely used biopesticide producer in the biological control market. It is very critical for the Bt pesticide industry to be able to achieve a high yield in the Bt fermentation process in order to reduce its cost and compete with chemical pesticides in the market. We review the overall development of Bt fermentation process research and provide our point of view for the future research opportunities and potential improvements. This minireview covers the areas of fermentation physiology, growth dynamics and high-yield process control. It is pointed out that many studies aimed to improve spore count and process research focusing on toxin protein yield is lacking. In addition, significant development opportunities reside in the process development for the genetically engineered Bt strains expressing multiple toxin proteins.

Bacillus thuringiensis↗

PubMed1997

Amino acid changes in a unique sequence of bacteriophage T7 DNA polymerase alter the processivity of nucleotide polymerization.

T7 gene 5 DNA polymerase forms a complex with Escherichia coli thioredoxin (its processivity factor), and a 76-amino acid sequence (residues 258-334), unique to gene 5 protein, has been implicated in this interaction. We have examined the effect of amino acid substitution(s) in this region on T7 phage growth and on the interaction of the polymerase with thioredoxin. Among the mutations in gene 5, we found that a substitution of either Glu or Ala for Lys-302 yielded a protein that could not complement T7 phage lacking gene 5 (T7Delta5) to grow on E. coli having reduced thioredoxin levels. One triple mutant (K300E,K302E,K304E) could not support the growth of T7Delta5 even in wild type cells. This altered polymerase is stimulated 4-fold less by thioredoxin than is the wild type enzyme and the polymerase-thioredoxin complex has reduced processivity. The exonuclease activity of the altered polymerase is not stimulated to the same extent as that of the wild type enzyme by thioredoxin. The observed dissociation constant of the gene 5 protein K(300,302,304)E-thioredoxin complex is 7-fold higher than that of the wild type complex. The altered polymerase also has a lower binding affinity for double-stranded DNA.

Bacteriophage T7↗

PubMed1997

Protection of ischemic preconditioning is dependent upon a critical timing sequence of protein kinase C activation.

The protection of ischemic preconditioning (PC) appears to be triggered by activation of receptors which couple to protein kinase C (PKC) during the brief ischemia. Previous experiments, however, suggest that phosphorylation of PKC's substrates is not required for the myocytes to enter the preconditioned state. Because of the fundamental importance of this observation, the present study was designed to stringently test when phosphorylation must occur during a PC protocol. We used an in vitro rabbit heart which permitted precise control of the timing of exposure to staurosporine (STA), a reversible blocker of PKC's kinase activity. In control hearts a 30-min regional coronary occlusion followed by 2 h of reperfusion resulted in 31.4 +/- 1.5% infarction of the region at risk, and STA (100 nM) had little effect. PC with 5 min of global ischemia and 10 min of reperfusion reduced infarction to 11.4% (P < 0.01 v control). STA starting 5 min before and ending 5 min after the 5-min PC ischemia did not block protection (14.1 +/- 1.7% infarction, P < 0.01 v control). When the PC protocol was changed to 5 min ischemia/20 min reperfusion, STA still could not block protection even though the infusion continued for 15 min after the PC ischemia. However, when a 15-min STA infusion was initiated 5 min before the 30-min ischemic period. PC's protection was totally blocked. Moreover this late infusion of STA continued to block protection even when the PC stimulus was amplified by three cycles of 5-min ischemia/10-min reperfusion. These observations indicate that kinase activity is not required to put the rabbit heart into a preconditioned state suggesting that some process upstream of PKC's kinase is responsible for the triggering and memory of PC.

Animals↗

PubMed1997

Attenuation of S-T segment elevation during repetitive coronary occlusions truly reflects the protection of ischemic preconditioning and is not an epiphenomenon.

Attenuation of S-T segment elevation between the first and subsequent balloon inflations of a coronary angioplasty procedure has been assumed to indicate a transition to a preconditioned state, but there has been no validation of this assumption. Open-chest rabbits were instrumented with a coronary snare and epicardial electrode. The coronary artery was occluded twice for 5 min with each occlusion followed by 10 min of reflow before a final 30 min occlusion. The evolving S-T elevation was quantitated as the voltage-time integral. For the first coronary occlusion total S-T segment elevation averaged 40.8+/-5.4 mV x min, significantly greater than 26.2+/-4.6 mV x min for the second occlusion (p < 0.001). There was no further change during the initial 5 min of the third occlusion (24.5+/-4.5 mV x min). When the protection of ischemic preconditioning was blocked by intravenous infusion of 8-(p-sulfophenyl)theophylline, an adenosine receptor antagonist, attenuation of S-T segment elevation was no longer apparent. When preconditioning was pharmacologically triggered by tyramine rather than ischemia, there also was no alteration in S-T segment elevation among the 3 occlusions. Therefore, S-T elevation was diminished during the second episode of ischemia only when a transition occurred from non-preconditioned to preconditioned state between occlusions. An attenuated S-T segment is a valid marker for the presence of the preconditioned state.

Animals↗