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Biomedical subjects

M Zhao

Publications and source records attributed to M Zhao.

At least 253 records · Page 14Linked to original sources
PubMed1997

[Effects of cigarette smoke extract on proliferation and ET-1 release of airway smooth muscle cells].

OBJECTIVE: To investigate whether the effect of smoking on airway smooth muscle cells (ASMC) is mediated by the autocrine action of endothelin-1 (ET-1). METHODS: Abbit ASMC was cultured exposed to cigarette smoke extract (CSE), we examined the mitogenic effect CSE on ASMC in vitro and whether the ETA receptor antagonist JKC-301 can inhibit this effect. RESULTS: The exposure of ASMC to 10% and 30% CSE resulted in obvious cytotoxity. The viability of ASMC was decreased, the lipid peroxides (MDA) formation was increased, and the release of lactate dehydrogenase (LDH) into supernatant was enhanced. 5% CSE significantly enhanced the cultured ASMC[3H]-thymidine (3H-TdR) incorporation by 59.9% (P < 0.01) over control. The ASMC proliferative response to 5% CSE was dose-dependently inhibited by JKC-301. Moreover, 5% CSE evoked time-dependent release of endogenous ET-1 from ASMC. CONCLUSION: These data demonstrate that 5% CSE mediates ASMC proliferation via release and autocrine mitogenic action ET-1.

Administration, Inhalation↗
PubMed1997

[Radionuclide scintigraphy in etiologic diagnosis of gastrointestinal bleeding in children].

OBJECTIVE: To assess the role of radionuclide scintigraphy in etiologic diagnosis of gastrointestinal bleeding in children, especially in detecting the cases of Meckel's diverticulum or double intestine. METHODS: 99mTc-pertechnetate abdominal scintigraphy was undertaken in 26 children with history of gastrointestinal bleeding. Additional 99mTc-RBC scintigraphy was performed in 12 cases who gave a negative 99mTc-pertechnetate scintigraphy as they had the signs of active bleeding. The final diagnosis of all cases was proved by surgery and pathology or endoscopy. RESULTS: In detecting Meckel's diverticulum and double intestine, the sensitivity, specificity and accuracy of 99mTc-Pertechnetate scintigraphy were 85. 7% (12/14), 91.7% (11/12) and 88.5% (23/26) respectively. CONCLUSION: Radionuclide scintigraphy may be the first procedure to explore the etiology in the lower digestive tract.

Child↗
PubMed1996

Testicular toxicity evaluation of arsenic-containing binary compound semiconductors, gallium arsenide and indium arsenide, in hamsters.

The testicular toxicities of gallium arsenide (GaAs), indium arsenide (InAs) and arsenic trioxide (As2O3) were examined by repetitive intratracheal instillation using hamsters. GaAs (7.7 mg/kg) and As2O3 (1.3 mg/kg) were instilled twice a week a total of 16 times and InAs (7.7 mg/kg) was instilled a total of 14 times. GaAs caused testicular spermatid retention and epididymal sperm reduction, though the degrees were less severe than those in rats shown in our previous experiment. InAs and As2O3 did not show any testicular toxicities. Serum arsenic concentration in GaAs-treated hamsters was less than half of that in As2O3-treated hamsters in which no testicular toxicities were found. Serum molar concentration of gallium was 32-times higher than that of arsenic in GaAs-treated hamsters. Therefore gallium may play a main role in the testicular toxicity of GaAs in hamsters.

Animals↗
PubMed1996

Human APOE protein localized in brains of transgenic mice.

Transgenic mice carrying the three common human apolipoprotein E (APOE) alleles have been developed. In this study, brains of the transgenic mice have been analyzed by in situ histohybridization, immunohistochemistry, and immunoblots to determine sites of gene expression, to identify specific brain cells associated with human apoE protein, and to determine the relative concentrations of the human apoE. Results indicate that (1) human APOE mRNA and apoE protein occur in the gray and white matter of transgenic mouse brains; (2) in the hippocampus of transgenic brains, human apoE protein reacts immunologically within the same cells as the glial fibrillary acidic protein (GFAP), a specific marker for astrocytes; and (3) concentrations of the apoE isoforms determined in three heterozygous transgenic brains range from 22 to 250 pmol/g wet weight of brain.

Alleles↗
PubMed1996

Testicular toxicity of gallium arsenide, indium arsenide, and arsenic oxide in rats by repetitive intratracheal instillation.

The testicular toxicities of two compound semiconductor materials, gallium arsenide (GaAs) and indium arsenide (InAs), and arsenic oxide (As2O3) were examined in rats by repetitive intratracheal instillation of these substances in suspension twice a week, a total of 16 times. A single instillation dose was 7.7 mg/kg in the GaAs and the InAs groups and 1.3 mg/kg in the As2O3 group. A significant decrease in sperm count and significant increase in the proportion of morphologically abnormal sperm were found in the epididymis in the GaAs group. Especially, abnormal sperm with a straight head increased markedly in this group. In the GaAs-treated rats, there was 40-fold increase in the degenerating late elongated spermatids at the postspermiation stages, stages IX, XI, and XI. From these results, it is indicated that GaAs disturbed the spermatid head transformation at the late spermiogenic phases and caused spermiation failure. InAs caused a sperm count decrease in the epididymis, though its testicular toxicity was relatively weak compared with that of GaAs. As2O3, a probable dissolution arsenic product of GaAs and InAs in vivo, did not show any testicular toxicities in this study. It seems likely that, along with arsenics, gallium and indium play a role in the testicular toxicities of GaAs and InAs.

Animals↗
PubMed1996

Distribution of [3H] alpha, beta-methylene ATP binding sites in pulmonary blood vessels of different species.

Purinergic neurotransmission has been reported to take part in the regulation of pulmonary vascular resistance in many species. The receptor which mediates the contraction of blood vessels by ATP was defined as P2X-purinoceptors in pharmacological studies. In the present study, autoradiographic localization of P2X-purinoceptors was carried out in pulmonary blood vessels from rat, guinea-pig, rabbit, piglet and human by using [3H] alpha, beta-methylene ATP ([3H] alpha, beta-MeATP) as the radioligand. Autoradiographs showed that all the pulmonary arteries had been labelled with [3H] alpha, beta-MeATP. The specific binding sites were only associated with the smooth muscle of the blood vessels. Semi-quantitation of the autoradiographs revealed significant differences in the densities of P2X-purinoceptors amongst the vessels studied, both regional and interspecific. Generally, intrapulmonary arteries were labelled more heavily than the main pulmonary arteries, and the medium- and small-sized arteries had higher densities of P2X-purinoceptor than the large muscular arteries. The veins were sparsely labelled, except that rat intrapulmonary veins were labelled moderately. The results from this study provide: (1) direct evidence for the existence of P2X-purinoceptors in pulmonary vasculature, (2) a semi-quantitative estimation of the relative density of P2X-purinoceptors in pulmonary vessels of different sizes; and (3) a comparison of the P2X-purinoceptor densities among the species studied. Furthermore, the distribution of the P2X-purinoceptors is consistent with known pharmacological responses elicited by ATP in these vessels.

Adenosine Triphosphate↗
PubMed1996

Characterization and autoradiographic localization of [3H] alpha,beta-methylene ATP binding sites in cat urinary bladder.

1. The characteristics and distribution of [3H] alpha,beta-methylene ATP ([3H] alpha,beta-MeATP), a radioligand for P2X-purinoceptors, binding sites in cat urinary bladder detrusor were examined. 2. Saturation analysis revealed that, in cat bladder membrane preparations, only one population of binding sites with high affinity (Kd = 1.8 nM) was present, in contrast to other species where both high-and low-affinity binding sites are present. Another feature is that the density of the binding sites in the cat bladder (Bmax = 21.2 pmol/mg protein) is considerably higher (about 2-fold) than the high-affinity binding component in the rat bladder membrane preparations. 3. Displacement experiments with unlabelled purinoceptor ligands indicate that [3H] alpha,beta-MeATP mainly binds to P2X-purinoceptors. The order of binding displacement activity was: alpha,beta-methylene ATP, beta,gamma-methylene ATP > 2-methylthioATP > ATP > suramin and L-beta,gamma-methylene ATP > > adenosine. 4. Autoradiographic study demonstrated dense specific binding sites of [3H] alpha,beta-MeATP on detrusor smooth muscle of cat bladder. 5. The results of this study are consistent with pharmacological studies for the existence of P2X-purinoceptors in cat bladder.

Adenosine Triphosphate↗
PubMed1996

Properties of tri- and tetracarboxylate Ca2+ indicators in frog skeletal muscle fibers.

Recently a number of lower-affinity fluorescent Ca2+ indicators have become available with principal absorbance bands at visible wavelengths. This article evaluates these indicators, as well as two shorter wavelength indicators, mag-fura-5 and mag-indo-1, for their suitability as rapid Ca2+ indicators in frog skeletal muscle fibers. With three lower-affinity tricarboxylate indicators (mag-fura-5, mag-indo-1, and magnesium orange), the change in fluorescence in response to an action potential (delta F) appeared to track the myoplasmic Ca2+ transient (delta[Ca2+]) without delay. With three lower-affinity tetracarboxylate indicators (BTC, calcium-orange-5N, and calcium-green-5N) and one tricarboxylate indicator (magnesium green), delta F responded to delta[Ca2+] with a small delay. Unfortunately, with the tetracarboxylate indicators, other problems were detected that appear to limit their usefulness as reliable Ca2+ indicators. Surprisingly, delta F from mag-fura-red, another tricarboxylate indicator, was biphasic (with 480 nm excitation), a feature that also greatly limits its usefulness. With several of the indicators, estimates were obtained for the myoplasmic value of KD, Ca (the indicator's dissociation constant for Ca2+) and found to be elevated severalfold in comparison with the value measured in a simple salt solution. These and other problems related to the quantitative use of Ca2+ indicators in the intracellular environment are evaluated and discussed.

Action Potentials↗
PubMed1996

Inhibition of sarco-endoplasmic reticulum calcium ATPases (SERCA) by polycyclic aromatic hydrocarbons: lack of evidence for direct effects on cloned rat enzymes.

Previous studies have demonstrated that immunosuppressive polycyclic aromatic hydrocarbons (PAHs) disrupt Ca2+ homeostasis leading to inhibition of the Ca(2+)-dependent pathways of T cell and B cell activation. The sustained Ca(2+)-elevation produced by immunosuppressive PAHs may result from the inhibition of Ca(2+)-ATPases in the endoplasmic reticulum (SERCA). The purpose of the present study was to determine whether PAHs directly inhibit cloned SERCA enzymes, and whether there is any selectivity for certain isoforms. PAHs were examined for their effects on purified cloned rat SERCA enzymes, including SERCA1, SERCA2a and SERCA3, transiently expressed in human embryonic kidney (HEK) cells. Results showed that known SERCA inhibitors, thapsigargin (100 nM) and 2,5-di(t-butyl)-1,4-benzohydroquinone (10 mumol), completely inhibited all rat SERCA isoforms, whereas 7,12-dimethylbenz(a)anthracene, benzo(a)pyrene, benzo(e)pyrene, anthracene, 3-methyl-cholanthrene, 9,10-dimethylanthracene and benz(a)anthracene at concentrations as high as 10 mumol appeared to have little inhibitory effect on any of the SERCA. The results demonstrating that PAHs do not inhibit cloned SERCA enzymes suggest that metabolism may be required for PAH-induced inhibition, or that other cellular elements, not present in the HEK transfection model, may be required for activity.

Adenosine Triphosphate↗
PubMed1996

Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo.

Nuclear magnetic resonance (NMR) non-invasively measures the apparent diffusion coefficient (ADC) of water, which is sensitive to the biophysical characteristics of tissue. Because anti-cancer treatment alters tumour pathophysiology, tumour ADC may be altered by treatment. In order to test this hypothesis, ADC was measured in s.c. implanted murine RIF-1 tumours before and up to 9 days after treatment with cyclophosphamide. A dose-dependent, reversible increase in tumour ADC was observed after cyclophosphamide treatment, which is consistent with an increase in the fraction of interstitial water due to treatment-induced cell death. Because tumour water ADC is increased substantially at a time when there is no change in tumour volume for a dose which produces minimal cell kill, its measurement could provide a novel means for early detection of response to anti-cancer therapy. If the changes in ADC observed in the present study are evident for commonly used anti-cancer therapies in different tumour types and specific to a therapeutic response, the approach could be broadly applicable as a response predictor since magnetic resonance imaging can be used to measure ADC in human tumours.

Animals↗
PubMed1996

The amplitude and time course of the myoplasmic free [Ca2+] transient in fast-twitch fibers of mouse muscle.

Bundles of 10-100 fibers were dissected from the extensor digitorum longus muscle of mouse, mounted in an apparatus for optical recording, and stretched to long sarcomere length (> or = 3.6 microns). One fiber within the bundle was microinjected with furaptra, a fluorescent indicator that responds rapidly to changes in myoplasmic free [Ca2+] (delta [Ca2+]). Twitches and brief tetani were initiated by external stimulation. At myoplasmic furaptra concentrations of approximately 0.1 mM, the indicator's fluorescence signal during fiber activity (delta F/F) was well resolved. delta F/F was converted to delta [Ca2+] under the assumption that furaptra's myoplasmic dissociation constant for Ca2+ is 98 microM at 16 degrees C and 109 microM at 28 degrees C. At 16 degrees C, the peak amplitude of delta [Ca2+] during a twitch was 17.8 +/- 0.4 microM (+/-SEM; n = 8) and the half-width of delta [Ca2+] was 4.6 +/- 0.3 ms. At 28 degrees C, the peak and half-width values were 22.1 +/- 1.8 microM and 2.0 +/- 0.1 ms, respectively (n = 4). During a brief high-frequency tetanus, individual peaks of delta [Ca2+] were also well resolved and reached approximately the same amplitude that resulted from a single shock; the initial decays of delta [Ca2+] from peak slowed substantially during the tetanus. For a single twitch at 16 degrees C, the amplitude of delta [Ca2+] in fast-twitch fibers of mouse is not significantly different from that recently measured in fast-twitch fibers of frog (16.5 +/- 0.9 microM; Zhao, M., S. Hollingworth, and S.M. Baylor. 1996. Biophys. J. 70:896-916); in contrast, the half-width of delta [Ca2+] is surprisingly brief in mouse fibers, only about half that measured in frog (9.6 +/- 0.6 ms). The estimated peak rate at which Ca2+ is released from the sarcoplasmic reticulum in response to an action potential is also similar in mouse and frog, 140-150 microM/ms (16 degrees C).

Animals↗
PubMed1996

Purification and characterization of ostrich pancreatic secretory trypsin inhibitor.

Ostrich pancreatic secretory trypsin inhibitor was isolated and purified using acid extraction, salt fractionation. SP-Sephadex C-50 and QAE-Sephadex A-25 chromatography and RP-HPLC. The amino acid sequence of ostrich PSTI showed it is a single peptide chain containing 69 amino acid residues with the highest homology between ostrich and chicken PSTI. The molecular weight, as determined by electronspray mass spectrometry and from amino acid sequence data, is 7650 Da. The isoelectric point of ostrich PSTI was found to be 5.7. Ostrich PSTI specifically inhibited ostrich and commercial bovine trypsin with Ki values of 8.0 x 10(-9) and 2.4 x 10(-7) M, respectively, while no inhibitory effects were observed with other serine proteases.

Amino Acid Sequence↗
PubMed1996

Regulation of alpha 1-, beta 1-, and beta 2-adrenergic receptors in rat heart by norepinephrine.

Previous studies suggest that the desensitization and downregulation of beta 1-adrenergic receptors (beta 1-AR) in the failing heart are the result of the elevated plasma catecholamine levels associated with this disease. To examine norepinephrine (NE)-induced regulation of cardiac adrenergic receptors, rats were infused with l-NE (200 micrograms.kg-1.h-1 for 7 days) or vehicle (0.001 N HCl) by implantation of osmotic minipumps. The technique of coverslip autoradiography was used to quantify alpha 1-adrenergic receptors (alpha 1-AR), beta 1-AR, and beta 2-AR in different tissue compartments of rat hearts. For measurement of beta-AR binding, sections were incubated with 70 pM [125I]iodocyanopindolol (ICYP) alone or in the presence of 5 microM dl-propranolol or 5 x 10(-7) M CGP-20712A (a beta 1-antagonist) and then set up for autoradiography. [3H]prazosin (1 nM) with or without phentolamine was used to study alpha-AR binding. Chronic infusion of NE induced a greater downregulation of beta 2-AR compared with beta 1-AR in all regions studied, including atrial and ventricular myocytes, coronary arterioles, and connective tissue. An 18% loss of beta 1-AR was seen only in atrial myocytes; beta 1-AR density actually increased 28% in ventricular myocytes following NE infusion. There was a 15% decrease in alpha 1-AR in ventricular myocytes, whereas no change in alpha 1-AR density was seen in myocardial arterioles. Our study demonstrates that beta 2-AR are more susceptible to NE-induced downregulation than beta 1-AR. Thus other mechanisms may be involved in the selective downregulation of beta 1-AR in certain forms of heart failure.

Animals↗
PubMed1996

Orientation and directed migration of cultured corneal epithelial cells in small electric fields are serum dependent.

Reorientation and migration of cultured bovine corneal epithelial cells (CECs) in an electric field were studied. Electric field application was designed to model the laterally directed, steady direct current electric fields which arise in an injured corneal epithelium. Single cells cultured in media containing 10% foetal bovine serum showed significant galvanotropism, reorienting to lie perpendicular to electric field vector with a threshold field strength of less than 100 mV/mm. Cells cultured in serum-free medium showed no reorientation until 250 mV/mm. Addition of EGF, bFGF or TGF-beta 1 singly or in combination to serum free medium significantly restored the reorientation response at low field strengths. Both the mean translocation rate and directedness of cell migration were serum dependent. Cultured in medium with serum or serum plus added EGF, single cells showed obvious cathodal migration at 100 mV/mm. Increasing electric field strength enhanced the cathodal directedness of single cell migration. Supplementing serum free medium with growth factors restored the cathodal directed migration of single cells and highest directedness was found for the combination of EGF and TGF-beta 1. Corneal epithelial sheets also migrated towards the cathode in electric fields. Serum or individual growth factors stimulated CEC motility (randomly directed). Applied fields did not further augment migration rates but added a vector to stimulated migration. Electric fields which are present in wounded cornea interact with other environmental factors and may impinge on CECs migration during wound healing. Therapies which combine the application of growth factors and electric fields may be useful clinically.

Animals↗
PubMed1996

Expression of inducible nitric oxide synthase in rat pulmonary Cryptococcus neoformans granulomas.

Rats, like humans, have extremely effective immune mechanisms for controlling pulmonary Cryptococcus neoformans infection. The mechanism(s) responsible for efficient immunity in rat experimental infection is unknown. Recently, induction of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) have been implicated as an important microbicidal mechanism by which activated macrophages effect cytotoxicity against microbes. In this report, we investigated the expression of iNOS in rat pulmonary cryptococcosis. Localization and regulation of NO production was studied by immunohistochemistry for iNOS in conjunction with immunohistochemistry for cell markers, cytokines, and cryptococcal capsular polysaccharide. iNOS immunoreactivity was detected in macrophages, neutrophils, vascular endothelium, and respiratory epithelium. Double-immunolabeling studies revealed that the most prominent iNOS immunoreactivity was localized to epithelioid macrophages (CD11b/c+) within granulomas; CD4+ and CD8+ T cells were numerous around granulomas but did not express iNOS. iNOS immunoreactivity was detected in a selective population of epithelioid macrophages within some granulomas but not others. iNOS- granulomas were identical to iNOS+ granulomas with respect to morphology and immunohistochemical profiles. Macrophage iNOS immunoreactivity was detected 1 week after infection in one out of four rats and was strongly expressed in all rats at 2 weeks (in up to 50 percent of the granulomas) but declined considerably by 25 days. iNOS expression coincided with granuloma formation and preceded a decrease in lung fungal burden, suggesting an anticryptococcal role for NO. By double labeling, cytokines that have been shown to promote (interferon-gamma, granulocyte/macrophage colony-stimulating factor) and inhibit (transforming growth factor-beta) macrophage iNOS expression were detected around iNOS+ granuloma. iNOS immunoreactivity was expressed in selected neutrophils (1 and 2 weeks) and endothelial cells (1 and 2 weeks and 25 days) in the inflamed lung. Airway iNOS immunoreactivity was limited to the luminal border of rare bronchiolar epithelial cells. iNOS immunoreactivity was not detected in uninfected rats. The present study provides the first evidence for association of iNOS expression with protective cellular responses to cryptococcal infection in vivo.

Animals↗
PubMed1996

Tenascin and type IV collagen expression in liver cell dysplasia and in hepatocellular carcinoma.

The extracellular matrix (ECM) located in and around tumors is different from normal organ stroma, and there is evidence that it is critically involved in carcinogenesis and malignant growth. Whereas an abnormal composition of ECM in hepatocellular carcinomas (HCC's) has previously been demonstrated, not much is known so far with respect to putative HCC precursor lesions. We have, therefore, systematically analyzed the immunohistochemical reactivity for two major ECM components, tenascin and type IV collagen, in three types of liver cell dysplasia (LCD), and compared the findings with patterns observed in HCC's of different types and grades. Tenascin reactivity was generally stronger in HCC's than in cirrhosis. In cirrhotic nodules harboring areas of LCD, tenascin expression was significantly lower in small cell LCD than in large cell LCD. Type IV collagen reactivity in and around HCC's decreased as a function of a lower differentiation grade. In both groups of cirrhosis, i.e. with or without HCC, cirrhotic nodules occupied by the small cell variant of LCD exhibited a significantly lower type IV collagen reactivity than those with large cell LCD or simple regenerative cells. Taken together these findings suggest that, similar to adenomatous hyperplasia, small cell LCD is characterized by an abnormal tenascin and type IV collagen expression, thus reflecting the defective ECM pattern observed in HCC's.

Carcinoma, Hepatocellular↗
PubMed1996

Copper/zinc and manganese superoxide dismutases in alcoholic liver disease: immunohistochemical quantitation.

Alcohol damage to the liver can, among other factors, be mediated through the action of toxic oxygen radicals generated by ethanol. Major antioxidants in the liver are copper/zinc and manganese superoxide dismutases (Cu/Zn- and Mn-SODs). In order to test whether SODs may be differentially expressed in alcoholic liver disease (ALD), biopsies from 45 patients with ALD were analyzed for qualitative and quantitative immunoreactivity of Cu/Zn- and Mn-SOD in hepatocytes. The overall amount of Cu/Zn-SOD reactivity was significantly lower in ALD than in control biopsies, whereas no difference was found for Mn-SOD. Staining for both enzymes was decreased in ballooned hepatocytes. Low Cu/Zn-SOD was correlated with advanced lattice-like perisinusoidal fibrosis. In hepatocytes forming cirrhotic nodules, SOD reactivity was similar to that of control cells. The results suggest that SODs may be differentially regulated in ALD, and that Mn-SOD, an inducible enzyme, may be involved in recovery and cell protection in ALD.

Adult↗