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Biomedical subjects

Y Shao

Publications and source records attributed to Y Shao.

At least 163 records · Page 9Linked to original sources

Medicagenic acid saponins from Aster batangensis.

Two new medicagenic acid saponins, named asterbatanoside J and K, were isolated from the roots of Aster batangensis. On the basis of chemical and spectral studies especially 2D NMR including COSY, HETCOR, HMQC, HOHAHA, TOCSY, ROESY and HMBC techniques, their structures were established as 3-O-beta-D-glucopyranosyl-(1--> 6)-beta-D-glucopyranosyl-2 beta, 3 beta-dihydroxy-olean-12-en-23 alpha, 28-dioic acid- 28-O-alpha-L-arabinopyranosyl-(1-->3)-alpha-L- rhamnopyranosyl-(1-->2)-beta-D-fucopyranoside and 3-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl- medicagenic acid-28-O-beta-D-xylopyranosyl-(-->4)-[alpha-L- arabinopyranosyl-(1 -->3)-alpha-L-rhamnopyranosyl-(1-->2) -beta-D-fucopyranside, respectively.

Carbohydrate Conformation↗

Receptor-mediated calcium signals in astroglia: multiple receptors, common stores and all-or-nothing responses.

Calcium signals following activation of P2Y purinergic, alpha 1 adrenergic, and muscarinic cholinergic receptors were examined in individual astroglial cells. ATP, phenylephrine and carbachol, each increased intracellular calcium levels ([Ca2+]i) to similar amplitudes in the presence or absence of extracellular Ca2+. The dose-response relationship showed that less than an order of magnitude increase in ligand concentration led to maximal increase in [Ca2+]i from basal levels. Simultaneous application of multiple ligands did not produce additive effects on [Ca2+]i. These data suggested that different ligands released Ca2+ from common stores and that each of the ligands could cause maximal release. Application of a second ligand immediately after the first ligand produced an additional Ca2+ rise, suggesting that the Ca2+ stores were rapidly refilled and that receptor desensitization rather than Ca2+ depletion accounted for the rapid decline of the Ca2+ peak. Caged IP3 produced Ca2+ signals similar to those produced by ligands. For a given cell, both caged IP3 and ligands sometimes produced only one level of partial Ca2+ increases, suggesting the presence of a pool of high IP3-sensitive stores. Together, our results indicate that neuroligands tend to generate an all-or-nothing Ca2+ release from IP3 sensitive stores. The interactions between different receptor systems most likely occur at the level of IP3 accumulation.

Adenosine Triphosphate↗

New triterpenoid saponins, asterbatanoside D and E, from Aster batangensis.

Two new triterpenoid saponins named asterbatanoside D and E have been isolated from Aster batangensis and their structures elucidated as 3-O-beta- D-glucopyranosyl-bayogenin-28-O-beta-D-glucopyranosyl-(1-->6)-beta -D- glucopyranoside and 3-O-6'-acetyl-beta-D-glucopyranosyl-bayogenin-28-O-beta-D- glucopyranosyl-(1-->6)-beta-D-glucopyranoside by means of MS, 1D and 2D NMR techniques (COSY, TOCSY, ROESY, HMQC, and HMBC), and chemical reactions.

Carbohydrate Conformation↗

Asteryunnanosides F and G: two new triterpenoid saponins from Aster yunnanensis.

Two new triterpenoid saponins, aster-yunnanosides F and G, were isolated from the roots of Aster-yunnanensis. Their structures were determined as oleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and 3-O-beta-glucopyranosyloleanolic acid-28-O-beta-D-glucopyranosyl-(1-->6)-[alpha-L-rhamnopyranosyl-(1-->2) ]- beta-D-glucopyranoside by spectral data, especially 2D NMR analysis including COSY, HETCOR, HOHAHA, and ROESY techniques, and chemical transformation.

Carbohydrate Sequence↗

Effects of angiotensin II generated by an angiotensin converting enzyme-independent pathway on left ventricular performance in the conscious baboon.

Human chymase is a serine proteinase that converts angiotensin (Ang) I to Ang II independent of angiotensin converting enzyme (ACE) in vitro. The effects of chymase on systemic hemodynamics and left ventricular function in vivo were studied in nine conscious baboons instrumented with a LV micromanometer and LV minor axis and wall thickness sonomicrometer crystal pairs. Measurements were made at baseline and after [Pro11DAla12] Ang I, a specific substrate for human chymase, was given in consecutive fashion as a 0.1 mg bolus, an hour-long intravenous infusion of 5 mg, a 3 mg bolus, and after 5 mg of an Ang II receptor antagonist. [Pro11DAla12]Ang I significantly increased LV systolic and diastolic pressure, LV end-diastolic and end systolic dimensions and the time constant of LV relaxation and significantly decreased LV fractional shortening and wall thickening. Administration of a specific Ang II receptor antagonist reversed all the hemodynamic changes. In separate studies, similar results were obtained in six of the baboons with ACE blockade (20 mg, intravenous captopril). Post-mortem studies indicated that chymase-like activity was widely distributed in multiple tissues. Thus, in primates, Ang I is converted into Ang II by an enzyme with chymase-like activity. This study provides the first in vivo evidence of an ACE-independent pathway for Ang II production.

Angiotensin I↗

Left atrial mechanical and biochemical adaptation to pacing induced heart failure.

OBJECTIVE: To determine the left atrial mechanical and biochemical adaptations to congestive heart failure, 10 dogs with rapid atrial and ventricular pacing and seven control dogs were studied. METHODS: Animals were instrumented with left atrial sonomicrometers and micromanometers and left atrial pressure-volume relationships were generated by phenylephrine boluses for maximum elastance (Emax) and end systolic elastance (Ees) calculations. Left atrial maximum volume, ejection fraction, and mean circumferential fibre shortening (Vcf) were compared at matched left atrial pressure. At necropsy, myosin heavy chain (MHC) isoforms from the left atrial body and appendage were separated with SDS-PAGE, stained with monoclonal antibodies to alpha and beta MHC, and quantified with laser densitometry. RESULTS: Left atrial ejection fraction and Vcf were significantly lower and maximum atrial volume and atrial systolic stroke volume were significantly greater in heart failure than in control. Emax was not significantly altered in heart failure, at 5.9(SD 2.9) v 4.5(1.6) mm Hg.ml-1 in controls. However, Vcf was lower (P < 0.05) and the A loop pressure-volume area (an index of eternal mechanical work performed by the left atrium) was greater (P < 0.05) in heart failure than in control dogs. The percent beta MHC in the left atrial body was greater in dogs with heart failure than in controls, at 42.6(9.8) v 17.3(9.0)%, P < 0.05. By contrast there was no significant beta MHC isoform switch in the left atrial appendage [14.4(7.6) v 17.9(9.7)%]. CONCLUSIONS: In this model of left atrial pressure and volume overload, there is significant upregulation of beta MHC in the left atrial body but not in the appendage and this isoform switch is associated with decreased velocity of left atrial contraction, increased atrial mechanical work, and unchanged force generation.

Animals↗

Preoperative segmental localization of focal hepatic lesion on MRI.

In order to evaluate the accuracy of preoperative segmental localization of hepatic mass lesions, 68 cases were prospectively studied and evaluated by the correlation of magnetic resonance imaging (MRI) and surgical findings. Right, middle and left hepatic veins were seen in 100%, 97% and 94% of the subjects respectively on MRI. The right and left portal veins were seen in 100% and 95.6% respectively. The accuracy in determining the segmental location of hepatic lesions was 89.7%. The accuracy could be increased to 91.3% if the lesion was located at single segment whereas it was only 86.4% when the lesion extended across several segments. It is possible to say that MRI is an important modality in the preoperative segmental localization of masses.

Adolescent↗

[Hepatectomy under liver normothermic ischemia in primary liver cancer patients associated with cirrhosis].

From Aug 1984 to Aug 1990, under one-shot normothermic interruption of Porta Hepatis, hepatectomy was performed in 115 patients with primary liver cancer (PLC). The incidence of associated cirrhosis was 82.8% with liver function in Grade A in 59.4% of patients and in Grade B in 40.6% of patients according to Pugh's ranking criteria. Hemihepatic vascular occlusion was preferred. Due precautions were taken to prevent postoperative hepatic failure, including continuous low-pressure oxygen inhalation, the use of antioxidants and dexamethasone. Post-operative complications were: Hydrothorax (7.8%), subphrenic abscess (3.5%), bite leakage and gastrointestineal bleeding (0.9%). There was no operative mortality and hospital mortality.

Adult↗

[Significance of CEA and CA242 in the diagnosis of colorectal carcinoma].

Carcinoembryonic antigen (CEA) is frequently used in the diagnosis of the colorectal carcinoma. CA242 is a novel unique tumor-associated antigen characterized by higher tumor specificity and sensitivity for colorectal cancer, as compared with other mucin antigens. In this study, preoperative levels of serum CEA and CA242 were measured in 63 cases of colorectal carcinoma. It was disclosed that the positive rate of CA242 was higher than that of CEA, particularly in patients with colon cancer. The combined determination of CEA and CA242 significantly increased the sensitivity and accuracy in the detection of colorectal cancer as compared with the use of CEA alone (P < 0.01). In patients with advanced disease the positive rate was markedly elevated, especially in patients with liver metastasis. The results indicate that the combined use of CEA and CA242 assays is an useful adjunct diagnostic measure for colorectal carcinoma, and is helpful in the assessment of the stage of the disease as well as in making treatment plan.

Adult↗

Enhancement of the antineoplastic effect of mitomycin C by dietary fat.

In the present study, we investigated the effects of high dietary fat on the growth of MX-1 heterotransplanted in athymic mice and its response to mitomycin C (MC) treatment. We found that high fat intake (25% corn oil, w/w) significantly increased tumor growth, but at the same time it also increased the tumor response to MC treatment compared to the control low fat diet (5% corn oil, w/w). In the tumors from mice fed either low (5% w/w) or high (25% w/w) fat, MC treatment induced oxidative challenge, indicated by significantly increased tumor total superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase peroxidase activities, as well as increased tumor lipid peroxidation. On the other hand, glutathione reductase activity was inhibited by MC treatment. Some of the enzymes which are known to activate MC, such as cytochrome b5 reductase and DT-diaphorase, were also induced in the tumor by high dietary fat intake. The enzyme activities in hepatic tissues were also altered by dietary fat and MC treatment but to a lesser extent. We conclude that high dietary fat intake could enhance the chemotherapeutic effect of MC by increasing MC-activating enzyme activities. The observed increase in lipid peroxidation after MC treatment in MX-1 human mammary carcinoma implanted in the nude mice could result from the observed inhibited glutathione reductase activity. It is tempting to speculate that this might be another antineoplastic mechanism for MC in addition to its known role as a bioreductive alkylating agent. Alternatively, glutathione reductase may be a target for bioreductive alkylation.

Animals↗

Protein splicing: an analysis of the branched intermediate and its resolution by succinimide formation.

Protein splicing involves the excision of an internal domain from a precursor protein and the ligation of the external domains so as to generate two new proteins. Study of this process has recently been facilitated by the isolation of a precursor and a branched intermediate from a thermophilic protein splicing element expressed in a foreign protein context. Two aspects of protein splicing are examined in this paper. We demonstrate a succinimide at the C-terminus of the spliced internal protein, implicating cyclization of asparagine in resolution of the branched intermediate, and we identify an alkali-labile bond in the branched intermediate. A revised protein splicing model based on these experimental results is presented.

Alkalies↗

Use of bremsstrahlung radiation to monitor Y-90 tumor and whole body activities during experimental radioimmunotherapy in mice.

BACKGROUND: Large differences in uptake between tumors, even for the same size, frequently observed in clinical and experimental radioimmunotherapy (RAIT), make monitoring of uptake in individual tumors imperative in comparing protocols. 90Y, widely-used for RAIT, emits no gamma radiation and absorption of the beta particle in tissue makes its detection unsuitable for in vivo monitoring. We tested whether bremsstrahlung radiation, produced when betas are decelerated by nuclei, could be used to monitor tumor uptake. METHODS: Subcutaneous human LS174T colon carcinoma tumors were grown in the upper thigh of nude mice and labeled antibody injected intracardially. With the tumor placed in the 2 cm-diameter aperture in a lead collimator, photons with energies from 100 to 200 keV transmitted through plastic, which absorbed the beta particles, were counted to maximize shielding from the rest of the body. The contribution of the normal tissues was subtracted by counting the non-tumor-bearing leg in the same position. Excretion was calculated from whole body activity determined by removing the collimator, placing the mouse in a syringe surrounded by tissue-equivalent material 10 cm from the detector, and counting photons between 200 and 740 keV to minimize the effect of tissue attenuation. RESULTS: For tumors larger than 0.14 gm, a good correlation was obtained between the in vivo bremsstrahlung measurements and the measurements on excised tumors in a calibrated well counter. Similar excretion rates observed in all the animals suggested that the whole body counting was accurate. CONCLUSIONS: Bremstrahlung detection appears feasible and reliable for monitoring both tumor and whole body activities.

Animals↗

A new method for determining dose rate distribution from radioimmuno-therapy using radiochromic media.

PURPOSE: To describe and evaluate a new, simple, inexpensive method for directly measuring the radiation dose and its spatial distribution generated from explanted tissues of animals previously injected with radiolabeled immunoconjugates or other agents. METHODS AND MATERIALS: This technique uses the newly developed radiochromic dye medium (Gafchromic) which responds reproducibly for therapeutic dose exposures, has high spatial resolution, does not require film processing, and is relatively insensitive to ambient light. We have evaluated the dose distribution from LS174T tumors and selected normal tissues in nude mice previously injected with 90Y labeled anti-carcinoembrionic antigen antibodies. Individual tissues from sacrificed animals are halved and the flat section of the tissue is placed onto the dosimetry media and then frozen. The dosimetry medium is exposed to beta and Bremsstrahlung radiation originating from the frozen tissues. The relative darkening of the dosimetry medium depends on the dose deposited in the film. The dosimetry medium is scanned with a commercial flatbed scanner and the image intensity is digitally stored and quantitatively analyzed. Isodose curves are generated and compared to the actual tissue outline. RESULTS: The absorbed dose distribution due to 90Y exposure show only slight gradients in the interior of the tissue, with a markedly decreasing dose near the edges of the tissue. In addition, the isodose curves follow the tissue outline except in regions having radii of curvature smaller than the range of the beta-particle (R90 = 5 mm). These results suggest that the shape of the tumor, and its curvature, are important in determining the minimum dose delivered to the tumor by radiation from 90Y monoclonal antibodies, and hence in evaluating the tumor response to the radiation. The dose and spatial dose distribution were calculated assuming that the total 90Y activity is distributed uniformly throughout a half ellipsoid. The calculated spatial dose distributions for the half ellipsoids were similar to those observed from the dosimetry media that had been exposed to radioactivity contained in the tumors. CONCLUSION: This method provides direct dose evaluation without elaborate summary calculations based on activity measurements from serial slices. The measured radiation dose actually indicates the dose rate at the time of animal sacrifice. Quantitative analysis of radiation emitted from the tissues is relatively fast, making it feasible to examine a number of tissues under a variety of conditions.

Animals↗

Glutamate blocks astroglial stellation: effect of glutamate uptake and volume changes.

Neurotransmitters which increase intracellular cAMP levels can cause cultured astroglia to change from a flat, polygonal shape to a stellate morphology. Little is known about how glial stellation can be regulated by other transmitters. In the present study, we demonstrated that L-glutamate blocked isoproterenol (ISO) or dibutyryl-cAMP induced stellation in astroglia. The glutamate inhibition was concentration dependent, with its maximal effect on > 90% of cells at 500 microM. Glutamate also reversed glial stellation within a short period (< 30 min). Glutamate uptake analogues, D-glutamate and D-aspartate, rather than receptor agonists, kainate and quisqualate, mimicked the glutamate effect. Likewise, the glutamate uptake blocker, D-thero-beta-hydroxyaspartate, blocked the glutamate effect. The glutamate inhibition was not a result of inhibition of cAMP formation, since norepinephrine, which inhibited 80% of ISO-stimulated cAMP, also caused glial stellation. Increases in extracellular K+ to 50 mM also reduced glial stellation, whereas 25 mM K+ had little effect. Since 25 mM K+ caused much greater depolarization than 400 microM glutamate, it was unlikely that the effects of both glutamate and high [K+] on glial stellation were due to membrane depolarization. Hypotonic treatment (120 mOsm) enhanced, whereas hypertonic treatment (520 mOsm) prevented, the glutamate reversal of glial stellation. Thus, glial swelling appeared to be a primary mechanism for the inhibitory effect of glutamate and high [K+] on glial stellation. This mechanism could also explain the observation that glutamate inhibited stellation induced by PMA, a PKC activator. Our data suggest that glutamate released from neurons during neuronal activity or pathology can be taken up by astrocytes and alter their morphology. Changes in glial morphology may in turn affect the volume and composition of the extracellular space and, as a result, neuronal activity.

Animals↗

Plasticity of astrocytes.

It is becoming apparent that astrocytes carry out a large number of different functions in brain and are able to modify their characteristics throughout life, that is they exhibit a high degree of plasticity in their phenotype. For example, the morphology of astrocytes changes markedly during neuronal migration, maturation, and degeneration. It is conceivable that these cells must constantly adjust their abilities to meet changes in brain environment. Several examples of astrocytic plasticity are presented in this review. First, the ability of astrocytes to recognize neuronal signals can change qualitatively as well as quantitatively; evidence suggests that the expression of glial receptors may be developmentally regulated by both intrinsic and extrinsic signals. Second, the expression of adrenergic receptors by astrocytes in adult brain can change in response to neuronal degeneration. The up-regulation of beta-adrenergic receptors in this case suggests that these receptors play a role in function of reactive astrocytes. Finally, glial morphology can be reciprocally regulated by neurotransmitters such as norepinephrine and glutamate. This reciprocal regulation may be significant since both beta-adrenergic receptors and glutamate transporters are found predominantly in astrocytes in the brain. The change in glial morphology may also affect neuronal activity by changing the volume of the extracellular space.

Adaptation, Physiological↗