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Biomedical subjects

Y Shao

Publications and source records attributed to Y Shao.

192 records · Page 11Linked to original sources
PubMed1992

Expression of adrenergic receptors in individual astrocytes and motor neurons isolated from the adult rat brain.

Attempts to show the distribution of adrenergic receptors (ARs) in autoradiographs of a brainstem motor nucleus following elimination of motor neurons yielded the unexpected result of an increase in beta-AR density. This increase was related to the gliosis accompanying the motor neuron degeneration. To determine the cells on which the AR subtypes were located, we dissociated cells from various regions of the adult rat brain and subsequently identified astrocytes by glial fibrillary acidic protein (GFAP) immunofluorescence. Slides containing the astrocytes were prepared for autoradiography using the nonselective beta ligand 125I-iodocyanopindolol (125ICYP) or the alpha 1 ligand 125IBE 2254 (125I-HEAT). The addition of the selective beta 1 blocker betaxolol or the beta 2 blocker ICI 118.551 to the incubation medium to displace 125ICYP binding was used to determine the binding of beta-AR subtypes. The great majority (greater than 88%) of isolated astrocytes sampled from the trigeminal motor nucleus, cerebral cortex, striatum, and cerebellum showed beta-AR binding. Astrocytes from the first three regions had similar average densities of beta-ARs, whereas the density in cerebellar astrocytes was 2- to 3-fold greater. The beta 2-AR subtype was proportionally greater than the beta 1 subtype in each region. Reactive astrocytes isolated from the trigeminal motor nucleus after degeneration of motor neurons showed a beta-AR density nearly 2-fold greater than resting astrocytes from the same region, with the beta 1 subtype showing the greater proportional increase. There was no beta-AR binding on trigeminal motor neurons. Astrocytes also showed a significant level of alpha 1-AR binding. No differences in alpha 1-AR binding were found in normal astrocytes isolated from the different regions, nor was there an increase in reactive astrocytes. In contrast, trigeminal motor neurons had an alpha 1-AR density nearly 10 times greater than astrocytes. In terms of the NE modulation of synaptic responses in motor neurons, the distribution of ARs would permit NE to act indirectly through alpha 1 and beta receptors on astrocytes and directly through alpha 1 receptors on motor neurons.

Animals↗
PubMed1992

Selection of reagents for human radioimmunotherapy.

Promising response rates are noted in patients with refractory Hodgkin's disease after radioimmunoglobulin therapy (RIT) with Yttrium-90 labeled polyclonal antiferritin. To explore the most efficacious selection of RIT reagents for use in humans, experimental animal data are reviewed for radiolabeled antiferritin and B72.3. Nude mice with subcutaneously implanted human malignancies provide an excellent primary screen for radiolabeled antibodies under consideration for use in humans. They provide information on the potential of a new reagent to target a human malignancy in vivo. The other determinant of the therapeutic ratio of RIT reagents--normal tissue toxicity--is best analyzed in large animals, such as dogs. Hematologic toxicity is dose limiting in all species and best predicted by a prescription of radiolabeled antibodies in mCi per kilogram body weight and the presence or absence of bone marrow targeting. Per cGy, RIT is more effective in causing BM damage in dogs than in rats. In dogs, bone marrow transplantation with autologous cryopreserved bone marrow cells or G-CSF treatment can accelerate hemopoietic recovery and granulopoiesis, respectively, after RIT. When dose escalation beyond bone marrow toxicity is performed, the liver (dog) or the intestinal tract (rat) become the next dose limiting tissue in dose escalation studies. Significant improvement in RIT results will be achieved when the normal liver uptake of chelated monoclonal antibody in dogs and in human patients can be prevented. The described animal models and continued investigations of RIT in patients with endstage Hodgkin's disease will allow for further improvement in the therapeutic ratio of RIT and the applicability of RIT in humans.

Animals↗
PubMed1992

Influence of loading conditions and contractile state on pulmonary venous flow. Validation of Doppler velocimetry.

BACKGROUND: Although recent studies suggest that pulmonary venous flow velocities may be used to evaluate left ventricular diastolic function, the influence of loading conditions and contractile state on the magnitude and pattern of pulmonary venous flow are poorly understood. METHODS AND RESULTS: Fourteen anesthetized open-chest mongrel dogs were instrumented with pulmonary venous flow probes, atrial sonomicrometer crystal paris, and high-fidelity micromanometers; transesophageal Doppler echocardiography was used to obtain simultaneous pulmonary venous flow velocities. Measurements were made over a wide range of left atrial pressure obtained by either intravascular volume infusion and inferior vena caval balloon inflation (n = 8), halothane inhalation (n = 6), or phenylephrine infusion (n = 5). There was an excellent correlation for pulmonary venous systolic (J) to diastolic (K) time integral between the Doppler and flow probe signal (r = 0.94; SEE, 0.18). When left atrial pressure was increased by volume infusion, there was a significant linear relation between mean left atrial pressure and the Doppler J/K peak (r = 0.64; SEE, 3.4 mm Hg) and flow velocity-time integral ratio (r = 0.75; SEE, 2.9 mm Hg). By contrast, when left atrial pressure was elevated by halothane-induced cardiac depression, there was no correlation. The independent determinants of the pattern of pulmonary venous flow (stepwise multiple linear regression analysis) under all conditions were atrial systolic shortening, aortic systolic pressure, heart rate, and left ventricular end-systolic dimension (cumulative r = 0.80). CONCLUSIONS: The pattern of pulmonary venous flow can be measured accurately with Doppler velocities and is differentially influenced by loading conditions and myocardial contractile state; in the absence of myocardial contractile dysfunction, the pattern of pulmonary venous flow may provide an estimate of left atrial pressure; and pulmonary venous flow is determined largely by atrial systolic function.

Animals↗
PubMed1991

Cytogenetic studies on peripheral lymphocytes of members from two multiple familial polyposis coli families.

Cytogenetic studies were carried out on peripheral lymphocytes of 30 members from two typical familial polyposis coli (FPC) families. It was found that, under low folic acid culture conditions, the chromosome aberration rate of FPC family members (10%) was much higher than that of the control group (2.3%). No significant difference in SCE was found between the two groups. We suggest that the chromosome aberration rate under certain conditions may be used as a parameter for the early detection of FPC in certain FPC families. The analysis of fragile sites sensitive to low folic acid in FPC family members revealed that besides the significant increase of 3p14, which is frequently seen in tumor patients, other unique sites (1p22, 1p32 and 6q21) were also present in most of the FPC patients. Fragile sites 1p22, 1p32 and 6q21 are located near certain well known oncogene loci; thus, they may have something to do with the pathogenesis of FPC. The actual relationship between these fragile sites and FPC remains to be elucidated.

Adenomatous Polyposis Coli↗
PubMed1991

[Isolation of human immunodeficiency virus (HIV) in epidemic area of HIV infection in Yunnan Province].

Blood were collected from HIV infected persons in epidemic area of HIV infection in Yunnan province for isolation of HIV. The coculture method was used for cultivating the virus and reverse transcriptase assay (RT) was the main method for detection of HIV. Of 25 seropositive, 24 asymptomatic and one PGL, 10 showed positive RT activity (greater than 5,000 cpm/ml and with a steadily increase, some to more than 40,000 cpm/ml). The results were confirmed by the detection of HIV1 p24 Ag (ELISA) and HIV1 POL and GAG gene sequence (PCR]. In accordance with the reports from other labs, the viruses isolated from these group of persons infect only PMCs, grew slowly with gradual increase of RT activity and caused no CPE. Efforts are making, at present, to rise the virus titer with better culture system. The amplified gene sequence of the isolates are under investigating.

Cells, Cultured↗
PubMed1991

A clinical and laboratory study of ciclopirox olamine (8% Batrafen) in the treatment of onychomycosis.

Ciclopirox olamine, a new synthetic substituted pyridone derivative, is an antimycotic agent with activity against a broad spectrum of pathogenic and nonpathogenic fungi. The clinical efficacy and safety of 8% ciclopirox olamine nail liquor were evaluated in 100 cases with finger (or great toe) onychomycosis. After 16 weeks and 24 weeks of treatment for finger and great toe onychomycosis, respectively, the overall therapeutic results were excellent in 36 cases, good in 17, fair in 24, and poor in 23. The period of treatment was extended in 31 cases; among them, 10 cases showed further improvement. As for in vitro inhibitory activity, the MIC of ciclopirox olamine against T. rubrum and C. albicans was 1 to 4 mg/L and 1 to 16 mg/L, respectively. This study indicates that 8% ciclopirox olamine nail liquor, with its satisfactory efficacy and lack of side effects, is a good remedy for onychomycosis.

Adult↗
PubMed1985

Cancer risks posed by aflatoxin M1.

The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

Aflatoxin M1↗
PubMedDate not supplied

The correlation between the gossypol contents in blood plasma, rete testis fluid, and cauda epididymal fluid following chronic treatment with gossypol in rats.

Concentrations of gossypol in blood plasma, rete testis fluid, and fluid from the caudia epididymidis were measured simultaneously by high performance liquid chromatography in rats treated with gossypol (15 mg/kg daily for 3 weeks). Antispermatogenic effects were demonstrated by loss of sperm motility in the cauda epididymidis and structural changes in the testis. It was found in these treated rats that concentrations of gossypol were lower in rete testis fluid compared with blood plasma but increased significantly in fluid from the cauda epididymidis. The results indicate a restriction of the blood-testis barrier to gossypol and its local concentration in the epididymis after fluid resorption.

Animals↗
PubMedDate not supplied

Resting and reactive astrocytes express adrenergic receptors in the adult rat brain.

Adrenergic receptor subtypes were localized in situ and in cells isolated from the trigeminal motor nucleus and several other brain regions. To study receptor expression in reactive astrocytes, motor neuron degeneration and a glial reaction were induced in the trigeminal motor nucleus by the injection of the toxic lectin Ricin communis into the trigeminal motor root. Autoradiography following incubation of tissue sections in the alpha 1-ligand 125IBE 2254 (HEAT) or the beta-ligand 125Iodocyanopindolol (ICYP) showed a decrease in alpha 1- and an increase in beta-adrenergic receptor binding in the region of neuronal degeneration and gliosis. Glial hypertrophy, rather than hyperplasia, appears to be mainly responsible for the increased beta-binding, since inhibition of mitosis with cytosine arabinofuranoside only partially blocked elevations of beta-adrenergic receptor binding and GFAP immunolabelling in reactive astrocytes. More direct evidence for the expression of adrenergic receptors in normal and reactive astrocytes was obtained by combined autoradiography and immunohistochemistry of cells dissociated from the cerebral cortex, striatum, cerebellum, and trigeminal motor nucleus of adult rats. More than 88% of GFAP-positive astrocytes showed varying densities of beta-adrenergic receptor binding. In each region, the beta 2-subtype was proportionally greater than the beta 1-subtype. Astrocytes also expressed a significant density of alpha 1-receptors. Trigeminal motor neurons did not show beta-receptor binding, but had a density of alpha 1-receptors tenfold greater than astrocytes. A model for the role of astrocytes in adrenergic receptor-mediated modulation of trigeminal motor neuron excitability is discussed.

Animals↗
PubMedDate not supplied

Production of neutrons from interactions of GCR-like particles.

In order to help assess the risk to astronauts due to the long-term exposure to the natural radiation environment in space, an understanding of how the primary radiation field is changed when passing through shielding and tissue materials must be obtained. One important aspect of the change in the primary radiation field after passing through shielding materials is the production of secondary particles from the breakup of the primary. Neutrons are an important component of the secondary particle field due to their relatively high biological weighting factors, and due to their relative abundance, especially behind thick shielding scenarios. Because of the complexity of the problem, the estimation of the risk from exposure to the secondary neutron field must be handled using calculational techniques. However, those calculations will need an extensive set of neutron cross section and thicktarget neutron yield data in order to make an accurate assessment of the risk. In this paper we briefly survey the existing neutron-production data sets that are applicable to the space radiation transport problem, and we point out how neutron production from protons is different than neutron production from heavy ions. We also make comparisons of one the heavy-ion data sets with Boltzmann-Uehling-Uhlenbeck (BUU) calculations.

Aerospace Medicine↗
PubMedDate not supplied

Load independence of radionuclide diastolic filling measurements in acute coronary occlusion.

BACKGROUND: An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease. METHODS AND RESULTS: The time constant of isovolumic relaxation (T) and the left atrioventricular gradient were measured with micromanometer catheters and diastolic left ventricular filling variables were measured with radionuclide ventriculography in nine anesthetized, open-chest dogs with an acute coronary artery occlusion. Infusion of the positive inotropic drug dobutamine hydrochloride (5 to 10 micrograms/kg/min) resulted in a 35% shortening of T and a 37% increase in the radionuclide first-half filling fraction (both p < 0.05), but no change in the left atrioventricular gradient. Conversely, infusion of the alpha-adrenergic vasoconstrictor phenylephrine hydrochloride (20 to 40 micrograms/min) augmented left ventricular load, increasing the atrioventricular gradient by 45%, but had no significant effect on T or the first-half filling fraction. Infusion of the direct-acting vasodilator, sodium nitroprusside (80 to 120 micrograms/min), was accompanied by a 14% lengthening of T with a corresponding 28% decrease in the first-half filling fraction (both p < 0.05). CONCLUSION: In an anesthetized, open-chest canine model of acute myocardial ischemia, the radionuclide first-half filling fraction reflects pharmacologically induced changes in the lusitropic state of the left ventricle with relative independence of loading conditions.

Acute Disease↗