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Biomedical subjects

R Tao

Publications and source records attributed to R Tao.

At least 37 records · Page 2Linked to original sources
PubMed1999

Human growth hormone increases apo(a) expression in transgenic mice.

Levels of Lp(a), an atherogenic lipoprotein that circulates in human plasma, are increased by the administration of growth hormone (GH). Many of the physiological effects of GH are mediated through insulin-like growth factor-1 (IGF-1), but ironically, IGF-1 treatment of humans is associated with a fall in plasma Lp(a) levels. To glean insight into the mechanism responsible for the GH-associated increase in plasma levels of Lp(a), we administered recombinant human GH (rhGH) to mice expressing a 370-kb human genomic fragment containing the apo(a) gene, 40 kb of 5'-, and 200 kb of 3'-flanking sequence [YAC-apo(a) transgenic mice]. The plasma levels of apo(a) and hepatic levels of apo(a) mRNA rose dramatically in the post-pubertal male mice in response to rhGH treatment. To determine whether the increase in plasma apo(a) was mediated by IGF-1, we treated castrated and noncastrated YAC-apo(a) transgenic mice with a continuous infusion of IGF-1 (100 microg/d) for 2 weeks, and plasma levels of apo(a) fell by approximately 50%. Thus the effects of rhGH and IGF-1 administration on plasma levels of apo(a) in the YAC-apo(a) transgenic mice simulate those seen in humans. The coordinate changes in apo(a) mRNA and plasma levels of apo(a) in response to rhGH and IGF-1 strongly suggest that these 2 hormones have independent effects on the transcription of the apo(a) gene.

Animals↗
PubMed1999

Transgenic mice expressing a human apolipoprotein[a] allele.

The most important determinant of plasma levels of Lp[a] are sequence differences at the highly polymorphic apolipoprotein[a] (apo[a]) locus. To define the sequences that mediate the regulation of apo[a] expression, we cloned a 370 kb DNA fragment that included a 130 kb apo[a] gene, and 40 kb 5'- and 200 kb 3'-flanking region from an individual with high plasma levels of Lp[a] using a YAC vector. This genomic clone was used to generate transgenic mice. In the YAC-apo[a] transgenic mouse, apo[a] was only expressed in the liver, as it is in humans. The mean serum level of apo[a] in 4-week-old YAC-apo[a] transgenic mice was 20 mg/dl. In the female mice the levels of apo[a] varied over a 1.5-fold range during the 4-day estrus cycle and the levels correlated directly with serum progesterone levels. The serum levels of apo[a] decreased to almost undetectable level in male mice after puberty and this decrease was reversed by castration. Ingestion of a high-fat diet resulted in a approximately 100-fold fall in hepatic apo[a] mRNA levels and >60-fold decrease in serum apo[a] levels. To delimit the control elements that mediate tissue-specific and sex hormone-responsive apo[a] transcription, we derived a reporter YAC in which 40 kb of 5' flanking sequences from the cloned apo[a] allele were linked to a luciferase reporter gene. Analysis of four independent transgenic lines revealed no hepatic luciferase expression, suggesting that important cis -acting elements located outside the apo[a] 5'-flanking region are necessary for in vivo expression of apo[a].

Alleles↗
PubMed1999

Hereditary absence of complement C5 in adult mice influences Wallerian degeneration, but not retrograde responses, following injury to peripheral nerve.

We have examined the role of complement component 5 (C5) in peripheral nerve fiber degeneration and regeneration, as well as in glial and neuronal cell responses in the central nervous system (CNS). Adult congenic mice lacking C5 (C5(-)) and the corresponding normal strain (C5(+)) were used. Macrophage recruitment as well as axonal and myelin sheath elimination were delayed from 1 to 21 days postinjury in C5(-) mice compared to the C5(+) group after sciatic nerve crush. Despite this, recovery of motor function was not delayed. In the CNS, microglial cells and astrocytes responded in the same way from 3 to 21 days after sciatic nerve injury in C5(-) and C5(+) mice, and the extent of neuron death following hypoglossal nerve avulsion was the same in both groups. These findings suggest that C5 and/or its derivatives play an important role in initiating the recruitment of macrophages to the injured nerve and, probably indirectly, in early remyelination of regenerating axons, but does not influence the longterm functional restoration or axotomy-induced nerve cell death. C5-derived molecules do not appear to participate in central glial cell responses to peripheral nerve injury. These findings elucidate new aspects on the functional role of the complement system in the peripheral nervous system following peripheral nerve injury.

Animals↗
PubMed1998

Low density lipoprotein receptor-negative mice expressing human apolipoprotein B-100 develop complex atherosclerotic lesions on a chow diet: no accentuation by apolipoprotein(a).

We have generated mice with markedly elevated plasma levels of human low density lipoprotein (LDL) and reduced plasma levels of high density lipoprotein. These mice have no functional LDL receptors [LDLR-/-] and express a human apolipoprotein B-100 (apoB) transgene [Tg(apoB+/+)] with or without an apo(a) transgene [Tg(apoa+/-)]. Twenty animals (10 males and 10 females) of each of the following four genotypes were maintained on a chow diet: (i) LDLR-/-, (ii) LDLR-/-;Tg(apoa+/-), (iii) LDLR-/-;Tg(apoB+/+), and (iv)LDLR-/-;Tg(apoB+/+);Tg(apo+/-). The mice were killed at 6 mo, and the percent area of the aortic intimal surface that stained positive for neutral lipid was quantified. Mean percent areas of lipid staining were not significantly different between the LDLR-/- and LDLR-/-;Tg(apoa+/-) mice (1.0 +/- 0.2% vs. 1.4 +/- 0.3%). However, the LDLR-/-;Tg(apoB+/+) mice had approximately 15-fold greater mean lesion area than the LDLR-/- mice. No significant difference was found in percent lesion area in the LDLR-/-;Tg(apoB+/+) mice whether or not they expressed apo(a) [18.5 +/- 2.5%, without lipoprotein(a), Lp(a), vs. 16.0 +/- 1.7%, with Lp(a)]. Histochemical analyses of the sections from the proximal aorta of LDLR-/-;Tg(apoB+/+) mice revealed large, complex, lipid-laden atherosclerotic lesions that stained intensely with human apoB-100 antibodies. In mice expressing Lp(a), large amounts of apo(a) protein colocalized with apoB-100 in the lesions. We conclude that LDLR-/-; Tg(apoB+/+) mice exhibit accelerated atherosclerosis on a chow diet and thus provide an excellent animal model in which to study atherosclerosis. We found no evidence that apo(a) increased atherosclerosis in this animal model.

Animal Feed↗
PubMed1998

Cloning and characterization of cDNAs encoding S-RNases from almond (Prunus dulcis): primary structural features and sequence diversity of the S-RNases in Rosaceae.

cDNAs encoding three S-RNases of almond (Prunus dulcis), which belongs to the family Rosaceae, were cloned and sequenced. The comparison of amino acid sequences between the S-RNases of almond and those of other rosaceous species showed that the amino acid sequences of the rosaceous S-RNases are highly divergent, and intra-subfamilial similarities are higher than inter-subfamilial similarities. Twelve amino acid sequences of the rosaceous S-RNases were aligned to characterize their primary structural features. In spite of their high level of diversification, the rosaceous S-RNases were found to have five conserved regions, C1, C2, C3, C5, and RC4 which is Rosaceae-specific conserved region. Many variable sites fall into one region, named RHV. RHV is located at a similar position to that of the hypervariable region a (HVa) of the solanaceous S-RNases, and is assumed to be involved in recognizing S-specificity of pollen. On the other hand, the region corresponding to another solanaceous hypervariable region (HVb) was not variable in the rosaceous S-RNases. In the phylogenetic tree of the T2/S type RNase, the rosaceous S-RNase fall into two subfamily-specific groups (Amygdaloideae and Maloideae). The results of sequence comparisons and phylogenetic analysis imply that the present S-RNases of Rosaceae have diverged again relatively recently, after the divergence of subfamilies.

Amino Acid Sequence↗
PubMed1998

Clinical and bacteriologic study of eighty-six patients with systemic lupus erythematosus complicated by infections.

OBJECTIVE: To investigate the clinical and bacteriologic features of patients with systemic lupus erythematosus (SLE) complicated by bacterial and/or fungal infections. METHODS: Statistical analysis was made on basis of the clinical and bacteriologic data of 86 patients with SLE complicated by bacterial and/or fungal infections. RESULTS: One hundred and thirty-three episodes of infections occurred in 86 patients with SLE, in which 51.13% were nosocomial infections and 76.69% occurred in the blood system, respiratory tract, lungs and urinary tract. Gram-negative bacilli, gram-positive cocci, fungal and other bacterial infections accounted for 39.85%, 31.58%, 18.80% and 9.77%, respectively. In the bacterial infections, 18.52% were caused by L-form bacteria and more than 60% of the patients had no apparent toxic manifestations. The odds ratio (OR) of infection increased significantly in patients with damaged functions of the heart, lungs and kidneys, and in those who received high-dosage steroids. CONCLUSIONS: Patients with SLE tend to develop nosocomial infections with gram-negative bacilli which are the most common pathogens. The clinical manifestations of the infection are atypical. Careful inspection and monitoring, timely collecting the specimens for L-form bacterial culture can reduce misdiagnosis and missed diagnosis of the infection.

Adolescent↗
PubMed1998

[Expression of interleukin-8 and its receptor in acute promyelocytic leukemia under all-trans retinoic acid treatment].

OBJECTIVE: To evaluate the clinical significance of expression of interleukin-(IL-8) and its type A receptor(IL-8RA) in acute promyelocytic leukemia(APL) patients under all trans-retinoic acid(ATRA) induction. METHODS: Serum IL-8 level of 18 APL patients were dynamically studied(ELISA). Fresh APL cells from 3 patients were cultured with ATRA(10(-6) mmol/L). Supernatant IL-8 level and IL-8RA expression on APL cells were measured by FACS. RESULTS: In vitro, IL-8 concentrations decreased 72 hours after incubation, while IL-8RA increased. In vivo, IL-8 increased more rapidly and markedly than temperature and WBC counts did before retinoic acid syndrome(RA-S) occurred. Serum IL-6 and IL-8 levels significantly increased when the patients suffered infection, and IL-8 increased even before fever. Both IL-8 and D-dimer increased while DIC progressed. CONCLUSION: ATRA inhibited IL-8 secretion of APL cells while increased the expression of IL-8RA. Monitoring serum IL-8 concentrations could predict the development of RA-S and infection. Increase of both IL-8 and D-dimer concentrations suggested DIC progression.

Adolescent↗
PubMed1998

Alteration in regulation of serotonin release in rat dorsal raphe nucleus after prolonged exposure to morphine.

Regulation of serotonin (5-HT) release may be altered during the development of opioid tolerance and dependency. To test this hypothesis, changes in extracellular 5-HT during prolonged administration of morphine were determined by microdialysis in the dorsal raphe nucleus (DRN) of freely behaving rats. Morphine or placebo pellets were implanted s.c. As compared to placebo, morphine pellets induced a sustained, approximately 50% increase in DRN 5-HT and a significant elevation in hot plate latency during the 12-hr period after implantation. One week later DRN 5-HT had returned to control levels, and implanting additional morphine pellets had no effect on 5-HT or hot plate latency. One day after removing the pellets from rats exposed to morphine for 2 wk, acute challenge with morphine (20 mg/kg, s.c.) had a significantly smaller effect on 5-HT in the DRN as compared to the placebo treatment group. Administration of naltrexone to rats implanted with morphine pellets for 2 wk induced signs of withdrawal and a significant decrease in DRN 5-HT. These results suggest that the regulation of 5-HT release is altered during the development of tolerance to morphine. Thus, DRN 5-HT may be one of the factors involved in the changes in physiology and behavioral state during opioid withdrawal.

Animals↗
PubMed1997

Influence of AMPA/kainate receptors on extracellular 5-hydroxytryptamine in rat midbrain raphe and forebrain.

1. The regulation of 5-hydroxytryptamine (5-HT) release by excitatory amino acid (EAA) receptors was examined by use of microdialysis in the CNS of freely behaving rats. Extracellular 5-HT was measured in the dorsal raphe nucleus (DRN), median raphe nucleus (MRN), nucleus accumbens, hypothalamus, frontal cortex, dorsal and ventral hippocampus. 2. Local infusion of kainate produced increases in extracellular 5-HT in the DRN and MRN. Kainate infusion into forebrain sites had a less potent effect. 3. In further studies of the DRN and nucleus accumbens, kainate-induced increases in extracellular 5-HT were blocked by the EAA receptor antagonists, kynurenate and 6,7-dinitroquinoxaline-2,3-dione (DNQX). 4. The effect of infusing kainate into the DRN or nucleus accumbens was attenuated or abolished by tetrodotoxin (TTX), suggesting that the increase in extracellular 5-HT is dependent on 5-HT neuronal activity. In contrast, ibotenate-induced lesion of intrinsic neurones did not attenuate the effect of infusing kainate into the nucleus accumbens. Thus, the effect of kainate in the nucleus accumbens does not depend on intrinsic neurones. 5. Infusion of alpha-amino-3-hydroxy-5-methyl-4-isoxazolaproprionate (AMPA) into the DRN and nucleus accumbens induced nonsignificant changes in extracellular 5-HT. Cyclothiazide and diazoxide, which attenuate receptor desensitization, greatly enhanced the effect of AMPA on 5-HT in the DRN, but not in the nucleus accumbens. 6. In conclusion, AMPA/kainate receptors regulate 5-HT in the raphe and in forebrain sites.

Animals↗
PubMed1997

Identification of stylar RNases associated with gametophytic self-incompatibility in almond (Prunus dulcis).

Stylar proteins of 13 almond (Prunus dulcis) cultivars with known S-genotypes were surveyed by IEF and 2D-PAGE combined with immunoblot and N-terminal amino acid sequence analyses to identify S-RNases associated with gametophytic self-incompatibility (SI) in this plant species. RNase activities corresponding to Sa and Sb, two of the four S-alleles tested, were identified by IEF and RNase activity staining. The Sa-RNase band reacted with the anti-S4-serum prepared from Japanese pear (Pyrus serotina); no reaction with the antiserum was observed with the Sb-RNase band. When the Sa-RNase band was excised from an IEF gel stained for RNase activity, subjected to SDS-PAGE, and detected by immunoblotting, it appeared that this band consisted of a single protein that reacted with the anti-S4-serum with M(r) of about 28 kDa. With 2D-PAGE and silver staining of the stylar extracts, all four S-proteins could be successfully distinguished from each other in the highly basic zone of the gel. Although Sb-, Sc-, and Sd-proteins had roughly the same M(r) of about 30 kDa, the Sc-protein seemed to be slightly smaller than the Sb-protein and slightly larger than the Sd-protein. In 2D-PAGE profiles as well, the Sa-protein had M(r) of about 28 kDa, apparently smaller than the other three proteins. A bud sport, in which one of the two S-alleles of the original cultivar is impaired, was visualized as a loss of Sc-protein, which is consistent with the previous pollination study. All four S-proteins reacted with the anti-S4-serum, probably because of the differing conformations of these S-proteins in the IEF and 2D-PAGE gels. The Sa-protein in 2D-PAGE appeared to be identical to Sa-RNase in IEF; both had the same M(r) and were reactive with the anti-S4-serum. N-terminal amino acid sequence analysis of the four S-proteins revealed that they were highly homologous to each other and similar to the S-RNases of Malus, Pyrus, Scrophulariaceae, and Solanaceae. Taken together, RNases in the style are strongly suggested to be associated with the gametophytic SI of almond. This is the first report identifying and characterizing S-RNase in almond.

Amino Acid Sequence↗
PubMed1996

Differential effect of NMDA on extracellular serotonin in rat midbrain raphe and forebrain sites.

The contribution of NMDA receptors to regulation of serotonin (5-HT) release was assessed by in vivo microdialysis in freely behaving rats. During infusion of NMDA (30, 100, and 300 microM) into the dorsal raphe nucleus (DRN), 5-HT was increased by approximately 25, 100, and 280%, respectively. Competitive and noncompetitive NMDA-receptor antagonists blocked this effect on DRN 5-HT. Infusion of NMDA (300 microM) into the DRN also produced an 80% increase in extracellular 5-HT in the nucleus accumbens. During infusion of NMDA (100 and 300 microM) into the median raphe nucleus (MRN), 5-HT was increased by approximately 15 and 80%, respectively. NMDA-receptor antagonists blocked this effect on MRN 5-HT. Infusion of NMDA into the MRN also produced a significant increase in hippocampal 5-HT. In contrast, infusion of NMDA into the nucleus accumbens, frontal cortex, or hippocampus produced small decreases in 5-HT in these forebrain sites. Taken together, these results suggest that NMDA receptors in the midbrain raphe, but not the forebrain, can have an excitatory influence on 5-HT neurons and, thus, produce increased 5-HT release in the forebrain. Furthermore, in comparison with the MRN, DRN 5-HT neurons were more sensitive to the excitatory effect of NMDA.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Differential regulation of 5-hydroxytryptamine release by GABAA and GABAB receptors in midbrain raphe nuclei and forebrain of rats.

1. Extracellular 5-hydroxytryptamine (5-HT) was determined in dorsal raphe nucleus (DRN), median raphe nucleus (MRN) and nucleus accumbens by use of microdialysis in unanaesthetized rats. 2. Infusion of the gamma-aminobutyric acid (GABA)A receptor agonist muscimol into DRN and MRN resulted in decreased 5-HT in DRN and MRN, respectively. Muscimol infusion into nucleus accumbens had no effect on 5-HT. 3. Infusion of the GABAA receptor antagonist bicuculline into DRN resulted in increased DRN and nucleus accumbens 5-HT. Bicuculline infusion into MRN had no effect on 5-HT. This suggests that endogenous GABA had a tonic, GABAA receptor-mediated inhibitory effect on 5-HT in DRN, but not in MRN. 4. Infusion of the GABAB receptor agonist baclofen into DRN produced a decrease in DRN 5-HT. Baclofen infusion into nucleus accumbens resulted in decreased nucleus accumbens 5-HT. This suggests that GABAB receptors are present in the area of cell bodies and terminals of 5-hydroxytryptaminergic neurones. 5. Infusion of the GABAB receptor antagonists phaclofen and 2-hydroxysaclofen had no effect on midbrain raphe and forebrain 5-HT. This suggests that GABAB receptors did not contribute to tonic inhibition of 5-HT release. 6. In conclusion, 5-HT release is physiologically regulated by distinct subtypes of GABA receptors in presynaptic and postsynaptic sites.

5,7-Dihydroxytryptamine↗
PubMed1996

Oral administration of insulin as poly(vinyl alcohol)-gel spheres in diabetic rats.

The oral administration of insulin in poly(vinyl alcohol)-gel spheres (PVA-GS), an oral dosage form with prolonged residence time in the ileum, was examined in streptozotocin-induced diabetic rats. Intragastric administration of PVA-GS containing insulin and a protease inhibitor, aprotinin or bacitracin, caused a significant and prolonged reduction of blood glucose levels, suggesting insulin absorption. The bioavailability of insulin estimated from the hypoglycemic effect was about 2% in the presence of either protease inhibitor. The release profiles of insulin and the protease inhibitors from the PVA-GS could be explained by Higuchi's plot, and the rates were similar to each other. The site dependency of insulin absorption in the intestinal tract was examined by an in situ loop method. Insulin absorption estimated by plasma insulin levels was larger in the ileum and the large intestine than in the jejunum. The prolonged residence time of PVA-GS in the absorption site, the lower intestine, and the synchronous release of insulin and the protease inhibitors from the PVA-GS are the two major explanations for the improved bioavailability of insulin administered as PVA-GS containing a protease inhibitor.

Administration, Oral↗