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Biomedical subjects

Y Shao

Publications and source records attributed to Y Shao.

At least 181 records · Page 10Linked to original sources
PubMed1994

Influence of acutely altered loading conditions on left atrial appendage flow velocities.

OBJECTIVES: The purpose of this study was to identify the effects of altered loading conditions on left atrial appendage flow velocities. BACKGROUND: Although studies have suggested that Doppler analysis of left atrial appendage blood flow may have clinical utility, the hemodynamic and cardiac mechanical determinants of left atrial appendage flow are poorly understood. METHODS: Transesophageal Doppler echocardiography was performed in eight atrially paced anesthetized dogs instrumented with sonomicrometers on the left atrial appendage and the left ventricular minor axis and with left atrial and left ventricular micromanometers. Left atrial appendage emptying and filling velocities corresponding to early and late ventricular diastole, respectively, were measured using volume expansion and phenylephrine infusion. RESULTS: Volume infusion caused a significant decrease in the early to late emptying and filling ratios (mean +/- SD 0.85 +/- 0.24 vs. 0.46 +/- 0.17 and 0.80 +/- 0.50 vs. 0.40 +/- 0.20, both p < 0.05). By contrast, phenylephrine infusion did not significantly alter either filling or emptying ratio. The independent determinants of each flow wave were identified with multiple regression analysis: early emptying velocity--time constant of left ventricular relaxation, left ventricular end-systolic dimension and aortic pressure (r = 0.75, p < 0.001); late emptying velocity--left ventricular peak positive time derivative of left ventricular pressure (dP/dt) and fractional shortening (r = 0.74, p < 0.001); early filling velocity--left atrial appendage shortening fraction (r = 0.45, p = 0.01) and late filling velocity--left atrial appendage lengthening rate and left ventricular fractional shortening (r = 0.56, p < 0.01). CONCLUSIONS: These results indicate that 1) both the magnitude and the pattern of left atrial appendage emptying and filling velocities are dependent on loading conditions, and 2) left atrial appendage velocities are influenced to a greater extent by changes in left ventricular than in left atrial appendage function. These findings may have implications for the pathogenesis of left atrial appendage thrombi.

Animals↗
PubMed1994

In vivo assessment of left atrial contractile performance in normal and pathological conditions using a time-varying elastance model.

BACKGROUND: Contractile function of the ex vivo, isolated left atrium (LA) has been described by a time-varying elastance, but this atrial chamber property has not been shown in vivo. METHODS AND RESULTS: Instantaneous LA pressure-volume (P-V) relations were studied in 12 anesthetized, autonomically blocked, atrially paced dogs. LA volume was calculated from orthogonal sonomicrometer pairs using a cast-validated formula. Data were collected during increases in LA pressure produced by a phenylephrine bolus (200 to 400 micrograms IV). Isochronal P-V points from 5 beats, representing a wide range of atrial pressures, were fitted by linear regression analysis (range of R2, .92 to .99). There were significant time-dependent increases in the slopes [E(t)] and small but statistically insignificant decreases in the volume axis intercepts [VO(t)] of the instantaneous LA P-V relations during atrial contraction; maximal elastance (Emax) occurred 29 +/- 16 milliseconds before atrial end systole (minimal LA volume). Emax was not significantly different than the slopes of either the nonisochronal end-systolic P-V relation (Ees) or the nonisochronal maximal P-to-V relation (EmaxPV): 5.5 +/- 2.8, 4.3 +/- 1.5, and 5.4 +/- 4.2 mm Hg/mL, respectively. In 7 dogs, data were collected both before and after a rapid infusion of calcium gluconate (1 to 2 g IV). Emax increased significantly with a calcium-induced increase in inotropic state (4.5 +/- 1.6 to 5.7 +/- 1.8 mm Hg/mL, P < .01), but the volume axis intercept was unchanged (3.6 +/- 0.7 versus 3.4 +/- 1.9, P = NS). In 4 additional dogs with heart failure (mean LA pressure, 26 +/- 6 mm Hg) produced by 3 weeks of rapid right ventricular pacing, LA stroke volume was significantly greater than and elastance determinations were similar to those of normal dogs. However, the effects of calcium infusion on LA function were attenuated in these animals. CONCLUSIONS: We conclude that (1) in the intact heart, LA contraction may be approximated by time-varying elastance with time-dependent changes in E(t) and that (2) LA systolic P-V relations using either the nonisochronal maximum P-to-V ratio or end systole may be useful as an estimate of Emax, are highly linear and sensitive to calcium-induced changes in inotropic state, and may be useful in identifying LA chamber adaptation to chronic hemodynamic loads.

Animals↗
PubMed1994

Terpenoid glycosides from the roots of Aster tataricus.

A new monoterpene glycoside, shionoside C, and a new oleanane-type triterpene glycoside, aster saponin G, were isolated from the roots of Aster tataricus. Their structures were elucidated on the basis of spectral and chemical methods. Shionoside C is L-endo-camphanol-8-3,5-isopropylidene-beta-D- apiofuranosyl-(1-6)-beta-D-glucopyranoside, aster saponin G is 3-O-[O-alpha-L-arabinopyranosyl-(1-6)-beta-D-glucopyranosyl]-2 beta, 3 beta, 16 alpha-trihydroxyolean-12-en-28-oic acid (asterogenic acid) 28-[O-beta-D-xylopyranosyl-(1-4)-alpha-L- rhamnopyranosyl-(1-2)-beta-D-xylopyranosyl]ester.

Bridged Bicyclo Compounds↗
PubMed1994

Neuroligand receptor heterogeneity among astroglia.

Astroglia are remarkedly diverse cells with respect to their pharmacological responsiveness and the processes regulated by neuroligand receptors. The results of single cell analyses indicate that astroglia continue to diversify in vitro. For example, the two daughter cells of a single division can exhibit qualitatively distinct responses to neuroligand application. These findings indicate that in contrast to most cells that "lock" their neuroligand receptor phenotype early in development, astroglia exhibit unusual plasticity. It is possible that this plasticity is necessary for immature astrocytes to respond to a changing neuronal environment during development. Interestingly, the increase in astroglial calcium following addition of neuroligands tends to originate from a localized area of the cell and then spreads as a wave that moves through the cell in a nondecremental manner. In situations in which astroglia are connected by gap junctions, the wave of calcium in one cell readily moves into the second without any obvious decrease in magnitude. Furthermore, astroglial calcium responses occur in an "all-or-none" manner reminiscent of neuronal action potentials. That is, the magnitude of an astroglial cell's calcium response appears relatively independent of the concentration of the ligand used or the density of receptors present on the cell. However, the probability of an astroglial cell responding to a given neuroligand is related to the density of receptors expressed and the concentration of the neuroligand applied. These characteristics suggest that, like neurons, signals received by an astrocyte are integrated and that when a threshold is reached the cell responds with a localized response that then propagates through that cell and into adjacent cells in a nondecremental manner. In neurons this is accomplished via depolarizations leading to action potentials and release of neurotransmitters. In astrocytes, distant signaling appears to occur via an "all-or-none" release of calcium, which then propagates through the cell and neighboring cells as a calcium wave. Our recent findings that neuroligands can modulate the opening and closing of astrocytic gap junctions suggest that specific pathways of astrocytic communication may exist. Overall, it is becoming evident that neuronal-glial signaling may be far more complex than previously imagined.

Action Potentials↗
PubMed1994

[A primary clinical trial of genital warts treated with domestic highly purified podophyllotoxin].

Genital warts (condyloma accunimata) are a kind of sexually transmitted disease (STD) caused by human papillomavirus (HPV). In this article, we report 75 cases of genital warts treated with highly purified podophyllotoxin. All volunteers were selected in our clinic and diagnosed according to typical skin lesions and positive 0.5% acetic acid test. Of the 74 cases 48 were male and 26 were female, with a mean age of 28.4 years (21-54). The average duration of disease was 4.4 months (2 weeks-3 years). All lesions were treated with 0.5% podophyllotoxin-ethanal solution topically 2 times per day for 3 successive days. The treatment was repeated if any warts persisted, but not more than 3 therapies in total were applied. The results showed that 41/48 (85.4%) of male and 23/26 (88.5%) of female patients were cured, the overall cure rate was 86.5% and the effectiveness rate (more than 50% lesions disappeared) was 96.15%. During another 3 months of follow-up, 9 male and 4 female patients (17.6% in total) experienced relapsed warts; these were cured with another treatment. Side effects including slight local irritation and erythema or superficial erosions were common, but 3 male and 2 female patients complained of sever pain and local swelling. All side effects were tolerable. It is concluded that our domestically produced highly purified podophyllotoxin is an effective, comparatively safe drug for the treatment of genital warts. It is also very simple to apply, and can be used for self-treatment.

Adult↗
PubMed1993

Regulation of astroglial responsiveness to neuroligands in primary culture.

Previous studies from this laboratory indicate that type-1 astroglia in primary culture are pharmacologically heterogeneous. Two competing hypotheses were proposed to explain the development of glial heterogeneity. First, that the heterogeneity may reflect stable subclasses of astroglia that express a set of receptor-signalling systems. Second, that astroglia can undergo qualitative changes in their expression of receptor-signalling systems with time in vitro. To distinguish between these two hypotheses, experiments were designed to examine neuroligand-evoked calcium responses within clones of type-1 astroglia. If stable and distinct subsets of astroglia were present, a clone derived from a single cell would exhibit uniform responses to a given set of neuroligands. Alternatively, if the pharmacological properties of astroglia underwent qualitative changes, astroglial clones should contain pharmacologically distinct cells. A video-based imaging system and the Ca2+ indicator dye Fura-2 were used to monitor receptor-mediated increases in Cai2+ upon receptor activation. Interestingly, only a fraction of the cells within a given clone responded to carbachol or histamine with an increase in Cai2+, whereas treatment with a P2Y purinergic receptor agonist generally increased Cai2+ in 100% of the cells within the clone. To examine the stability of the receptor signalling over time, individual astroglia within a number of clones were tested on different days for their ability to respond to neuroligands. The results of these experiments indicated that individual astroglial cells tended to lose their responsiveness to certain ligands such as carbachol and histamine as they developed responsiveness to others such as norepinephrine. Our data indicate that during development neurotransmitter receptors on astroglial cells are regulated by both internal and external mechanisms. Glial proliferation produces a variety of pharmacologically distinct astroglial cells. Exposure to neurotransmitters can qualitatively turn off some, but not all, astroglial receptor systems.

Adenosine Triphosphate↗
PubMed1993

Preclinical evaluation of intravenously administered 111In- and 90Y-labeled B72.3 immunoconjugate (GYK-DTPA) in beagle dogs.

B72.3, a monoclonal antibody with reactivity against human adenocarcinomas was obtained from the Cytogen Corporation in the form of an immunoconjugate coupled with linker-chelator GYK-DTPA by using proprietary carbohydrate directed site specific chemistry. The immunoconjugate was radiolabeled with indium-111 or yttrium-90. A preclinical analysis was performed in 10 normal beagle dogs. The pharmacokinetics of intravenously administered indium- and yttrium-labeled immunoconjugates were compared serially in blood, bone marrow and urine samples. Compared to 90Y less of the 111In label ended up in urine and more was found in blood and bone marrow. Indium-labeled B72.3 GYK-DTPA had relatively higher uptake in most glandular tissues than 111In-labeled antiferritin immunoconjugate. Bone marrow toxicity was the dose limiting side effect after intravenous infusion of 90Y-labeled B72.3 GYK-DTPA. Toxicity was also observed in the liver but not in other organ systems. Recently other investigators obtained similar results with these immunoconjugates in human patients. A preclinical pharmacokinetic analysis of radioimmunoconjugates in beagle dogs provided useful information regarding bone marrow toxicity, liver toxicity and in vivo instability of the immunoconjugate. Data suggest that for future trials in human patients, a more stable chelated immunoconjugate for yttrium is needed to achieve less liver uptake and a better correlation with the 111In-labeled product than the 90Y-labeled B72.3 GYK-DTPA used in this investigation.

Animals↗
PubMed1993

Fractionated intravenous administration of 90Y-labeled B72.3 GYK-DTPA immunoconjugate in beagle dogs.

B72.3, a monoclonal antibody with reactivity against human adenocarcinomas, was coupled with linker-chelator GYK-DTPA using carbohydrate mediated conjugation chemistry and radiolabeled with yttrium-90. Single and double intravenous injections of radioimmunoconjugate were compared for acute and late normal tissue toxicity in 15 beagle dogs. The second injection was given 4 or 8 days after the first. Pharmacokinetics of the radioimmunoconjugate in blood, bone marrow and urine were similar for first and second injections. Only bone marrow (acute) and liver (late) toxicity were observed. Both liver and bone marrow toxicity were decreased by fractionation of the injections. After double injections, the total equitoxic dose was 15 and 60% higher for bone marrow and liver toxicity, respectively. The mechanisms of normal tissue protection offered by fractionated radioimmunoglobulin therapy (RIT) remain to be defined. Fractionated RIT will have a better therapeutic ratio than single injection RIT, if antitumor effects appear to be less susceptible to fractionation than normal tissues.

Animals↗
PubMed1993

Comparative assessment of regional left atrial perfusion by laser Doppler and radionuclide microsphere techniques.

OBJECTIVE: The aim was to study the relation between left atrial microcirculatory flux, using laser Doppler flowmetry (LDF), and blood flow, using radiolabelled microspheres (MS). METHODS: Studies were done in five anaesthetised dogs. LDF probes were sewn to the appendage and body of the left atrium. Radionuclide spheres (15 microns) were used to quantitate blood flow at baseline, and during atrial pacing at 3.5 Hz, atrial fibrillation, and intravenous adenosine infusion (1 mg.kg-1 x min-1). RESULTS: In the left atrial body, both MS and LDF perfusion increased significantly during pacing and adenosine infusion; only LDF registered significant increases during atrial fibrillation. In the left atrial appendage, MS flow failed to increase significantly with any intervention and LDF perfusion increased significantly only during atrial fibrillation. There was a significant but weak correlation (r = 0.36, p < 0.05) between LDF and MS when data from all sample sites (n = 40) were compared, but good correlation when only baseline and pacing data were compared (r = 0.72, p = 0.0004, n = 20). In four additional dogs with heart failure [mean left atrial pressure 25.3(SD 7.4) mm Hg] produced by three weeks of rapid right ventricular pacing, flux values at baseline were increased significantly compared to control dogs and the responses registered by LDF to pacing, atrial fibrillation, and adenosine infusion were attenuated markedly. CONCLUSIONS: (1) Microcirculatory flux detected by LDF can identify the direction, and to a lesser extent, the magnitude of changes in regional atrial perfusion; and (2) LDF may be useful in identifying abnormalities of vasodilator reserve that accompany chronic left atrial myocardial dysfunction.

Animals↗
PubMed1993

The effect of cyclosporine treatment on the expression of genes encoding granzyme A and perforin in the infiltrate of mouse heart transplants.

Following activation of cytotoxic T cells and NK cells several genes encoding proteins putatively involved in cell-mediated cytotoxicity become expressed. The expression of genes encoding the cytotoxic T cell associated serine protease granzyme A and perforin was analyzed in cellular infiltrates of MHC mismatched (H-2d-->H-2k) heterotopic heart transplants both in immunosuppressed recipients treated with cyclosporine and in untreated recipients. Heart transplants were completely rejected by untreated animals on day 10 post-transplantation, whereas CsA treatment generally prolonged survival of the transplants beyond 30 days. In untreated recipients the number of granzyme A- and perforin-expressing cells in heart transplants increased from approximately 10 granzyme A-positive cells/mm2 and 1 perforin-positive cell/mm2 on day 2 posttransplantation to over 80 positive cells for both genes on day 5 posttransplantation. In contrast, these values remained always below 15 positive cells/mm2 for both genes between day 5 and day 30 posttransplantation in CsA-treated recipients. Comparison of the frequency of CD8+ T cells in the infiltrates showed that lower numbers of perforin and granzyme A-positive cells were mainly due to the immunosuppressive action of CsA rather than to reduced infiltration of transplants. The present study shows that expression of granzyme A and perforin gene can be used to discriminate between quiescent and activated cytotoxic cells also in immunosuppressed animals and further confirms that these can be used as sensitive markers for monitoring the fate of a transplant.

Animals↗
PubMed1993

Determination of left atrial volume using sonomicrometry: a cast validation study.

We developed a technique for left atrial (LA) volume estimation using two pairs of sonomicrometers sewn to the anteroposterior (LAX) and mediolateral (SAX) LA diameters and validated the method against water displacement of LA casts in 15 dogs. LA pressure was adjusted to a preselected level (5, 10, or 15 mmHg) by dextran infusion and was matched by postmortem infusion of casting resin (Conthane DPEN-18402). LA volume was modeled empirically as an ellipsoid of revolution without regression constants [(SAX)2(LAX)]. There was a strong correlation between the calculated LA volume and water displacement of the LA body [r = 0.87, standard error of estimate (SEE) = 3.3 ml, P = 0.0001] but a weaker correlation against water displacement of the entire LA (body+appendage, r = 0.81, SEE = 3.9 ml, P = 0.0003). The appendage volume fraction (appendage volume/total LA volume), as determined by water displacement of the casts, increased with increasing LA size (r = 0.78, P = 0.001). These data indicate that, in the normal canine heart, LA volume can be estimated accurately with high temporal and spatial resolution sonomicrometry using two atrial dimensions, and the contribution of appendage to total LA volume may become significant as the atrium enlarges.

Animals↗
PubMed1993

Influence of pericardium on left atrial compliance and pulmonary venous flow.

We studied seven open-chest anesthetized dogs to test the hypothesis that left atrial (LA) compliance is increased after pericardiectomy and to determine the effect of pericardiectomy on left atrial reservoir and conduit function. Two orthogonal sonomicrometer crystal pairs were used to estimate LA volume, and LA filling was assessed with a pulmonary vein (PV) flow probe. The left ventricular (LV) systolic (JFTI) and diastolic (KFTI) PV flow integrals were used as indexes of LA reservoir and conduit function, respectively. Diastolic LV transmitral flow was assessed with transesophageal Doppler echocardiography. Data were acquired over a wide range of intracardiac pressures and volumes obtained by intravenous hetastarch infusion both before and after pericardiectomy. The mean dynamic stiffness constant of the LA diastolic pressure-volume relation was significantly greater before pericardiectomy than afterwards (0.15 +/- 0.04 vs. 0.08 +/- 0.03 ml-1, P < 0.05). Data were analyzed before and after pericardiectomy at three matched levels of left atrial pressure (LAP; 7, 13, and 20 mmHg). The J-to-KFTI ratio increased significantly with volume infusion and was significantly less after pericardiectomy than before (1.2 +/- 0.7 vs. 1.2 +/- 0.6, 1.8 +/- 0.6 vs. 2.2 +/- 0.9, and 2.0 +/- 0.8 vs. 2.6 +/- 0.9 at low, mid, and high levels of LAP, respectively; P < 0.05 at mid and high levels of LAP). Peak early transmitral velocity increased with both volume infusion and pericardiectomy. We conclude that pericardiectomy increases LA compliance and early LV filling rate and is accompanied by a relatively greater augmentation in conduit than reservoir function of the left atrium.

Animals↗
PubMed1993

Altered left atrial compliance after atrial appendectomy. Influence on left atrial and ventricular filling.

Previous studies have shown regional differences in atrial distensibility. We studied 12 open-chest dogs to test the hypothesis that left atrial compliance is decreased after removal of the left atrial appendage and to determine the effect of altered atrial compliance on atrial reservoir and conduit function. Sonomicrometer crystal pairs were used to measure the long- and short-axis diameters of the left atrium over a wide range of intracardiac pressures and volumes obtained by intravenous hetastarch infusion both before and after suture ligation of the left atrial appendage (appendectomy). Pulmonary venous flow was measured with an ultrasonic flowmeter, and transmitral flow velocities were measured with transesophageal Doppler echocardiography. After appendectomy, the diastolic pressure-volume relation was shifted upward and to the left in six of seven dogs. The mean dynamic stiffness constant of the left atrial diastolic pressure-volume relation was significantly greater after appendectomy than before (0.20 +/- 0.11 [mean +/- SD] versus 0.14 +/- 0.08 ml-1, p < 0.01); the mean y intercept was slightly, but significantly, less after appendectomy (0.6 +/- 0.3 versus 1.3 +/- 0.6 mm Hg, p < 0.05). The left atrial reservoir volume (maximum minus minimum left atrial volume) was significantly less after appendectomy at matched left atrial pressures. The systolic to diastolic flow integral ratio of pulmonary venous flow (JFTI/KFTI), an index of the relative reservoir to conduit functions of the left atrium, increased significantly with volume infusion only before appendectomy; at matched left atrial pressure, JFTI/KFTI was significantly less afterwards.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Quantitative relationship between alpha 1-adrenergic receptor density and the receptor-mediated calcium response in individual astroglial cells.

alpha 1-Adrenergic receptor (alpha 1-AR) agonists elevate the intracellular calcium concentration ([Ca2+]i) in 60-80% of astroglia in vitro. Likewise, 60-70% of astroglia exhibit specific binding sites for the alpha 1-AR-selective antagonist (+-)-125I-[beta-(4-hydroxyphenyl)-ethylaminomethyl]tetralone. The density of alpha 1-AR binding sites varies markedly on individual cells, ranging from a few to > 2000 binding sites/1000 microns 2 of surface area. In the present study, we examined the relationship between the density of alpha 1-AR binding sites on astroglia and their ability to respond to alpha 1-AR agonists with a rise in [Ca2+]i. A video-based imaging system was used to monitor calcium responses in individual astroglial cells, which were subsequently assessed for their expression of alpha 1-ARs using receptor binding autoradiography. The ability of a given concentration of phenylephrine (PE) to elicit a calcium response correlated well with alpha 1-AR density (r = 0.94), i.e., the higher the receptor density the greater the probability that a given astroglial cell would respond to alpha 1-AR agonists. However, the amplitude of the calcium response did not correlate with the alpha 1-AR density. Cells with low alpha 1-AR density (< 10 binding sites/1000 microns 2) could generate a response with an amplitude comparable to that seen in cells with high alpha 1-AR density (> 1000 binding sites/1000 microns 2). To evaluate the relationship between receptor occupancy and calcium response, PE concentrations and alpha 1-AR density were varied while the calcium response in individual cells was monitored. Interestingly, for a given cell the amplitude of calcium response reached its maximum with a small step increase in the concentration of PE (< 5-fold), whereas the latency of the response decreased when PE concentrations were increased. Irreversible inactivation of alpha 1-ARs by phenoxybenzamine reduced the potency of PE but not the maximal calcium response. Cells that responded to 100 nM PE were able to generate a comparable response to 10 microM PE after inactivation of 90% of the total alpha 1-AR binding sites with phenoxybenzamine treatment. In summary, our results indicate that most astroglial cells express a substantial level of "spare" alpha 1-ARs that increase the sensitivity of these cells to alpha 1-AR agonists. Once activated, individual astroglial cells tend to generate a maximal [Ca2+]i elevation that is independent of the total alpha 1-AR density or the concentration of ligand.

Adrenergic alpha-Antagonists↗
PubMed1993

Surveillance and care of four Chinese hemophiliacs with human immunodeficiency virus (HIV) infection.

Four Chinese hemophiliacs with HIV infection have been followed up in Zhejiang Province since 1985. A plan for optimal care of HIV seropositive patients was proposed, including surveillance and care; clinical follow-up and preventive education of asymptomatic HIV seropositive patients; keeping the disease confidential so as not to stir up unnecessary social unease; propaganda and health education about acquired immunodeficiency syndrome (AIDS); treatment with traditional Chinese medicines; and regular surveillance of family members and medical personnel. This plan is regarded as feasible and effective for the prevention and control of AIDS in China.

Acquired Immunodeficiency Syndrome↗