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Biomedical subjects

Z Su

Publications and source records attributed to Z Su.

At least 91 records · Page 5Linked to original sources
PubMed1998

Effects of angiotensin II on intracellular calcium and contracture in metabolically inhibited cardiomyocytes.

Angiotensin II (A-II) is known to potentiate ischemic dysfunction during ischemia, but the mechanisms involved are not completely established. We examined the effects of A-II on intracellular calcium concentration ([Ca++]i) and cell contracture caused by metabolic inhibition in isolated adult rabbit ventricular myocytes. [Ca++]i was assessed by flow cytometry, using the Ca(++)-sensitive fluorescent probe, fluo-3. After 90 min of exposure to 2 mM cyanide (CN) and 0 glucose, there was a significant increase in myocyte [Ca++]i. This increase was slightly augmented in the presence of 100 nM A-II. In the presence of partial Na+/K+ ATP pump inhibition ([K+]o = 0.8 mM), there was a more significant increase in [Ca++]i associated with exposure to CN + A-II vs. CN alone. Similar results were obtained with CN plus 2-deoxyglucose, and the effect of A-II was inhibited by 10 microM 5-(N-ethyl-N-isopropyl)amiloride. Myocytes exposed to 2 mM CN and 0 glucose gradually developed contracture over a 3-hr period. Addition of 100 nM A-II significantly (P < .01) enhanced loss of rod shape morphology during 3 hr of CN exposure. Partial inhibition of the Na+ pump by exposure to 0.8 mM K+ had no effect on myocyte survival in the absence of CN, but augmented the harmful effect of A-II on cell contracture caused by CN exposure. This effect of A-II was completely reversed by the addition of 1 mM amiloride, a Na+/H+ exchange inhibitor. We conclude that A-II directly enhances cell injury during CN exposure in isolated rabbit ventricular myocytes. We postulate that this effect of A-II is mediated by stimulation of Na+/H+ exchange with resultant increased [Na+]i and subsequent [Ca++]i loading, possibly via reverse Na+/Ca++ exchange.

Angiotensin II↗
PubMed1997

Genetic and immunological adaptation of Heligmosomoides polygyrus in mice.

Two lines of Heligmosomoides polygyrus, QN and QA, were selected by passage, respectively, through naive and immune Quackenbush (Q) mice and their biology and capacity to induce immune responses in homologous Q and heterologous low- (SL) and high-responder (RH) mice were assessed. QA H. polygyrus survived the impact of otherwise protective immunity in Q mice better than did QN parasites, especially after a secondary infection. The enhanced survival of QA parasites was observed also in SL but not in RH mice. Infections with QA phenotypes induced a reduced antibody response and lower eosinophilia compared to QN parasites in Q mice. The total numbers of nucleated cells in the mesenteric lymph node (MLN) and spleen increased to different extents according to the genotype of the mice and the phenotype of parasite used: the increase was most profound in RH, least in SL and intermediate in Q mice; QN induced more lymphocytosis in the MLN and spleen than did QA parasite phenotypes. B cells from MLN and spleen, stained with fluorochrome-conjugated antibody against mouse Ig, showed increased intensity of fluorescence in the flow cytometric assay after infection with H. polygyrus, but to different degrees: the intensity increased most in RH and least in SL mice; more in Q mice infected with QN than with QA H. polygyrus. These results suggest that adaptation of parasites to immunity of the host is associated with reduction of their immunogenicity and is specific to the immune status and genotype of the host to which the parasites have become adapted.

Animals↗
PubMed1997

H-2 genes and resistance to infection with Heligmosomoides polygyrus in selectively bred mice.

Two lines of mice bred selectively for high resistance (RH) and susceptibility (SL) to reinfection with Heligmosomoides polygyrus demonstrated disparate levels of resistance to infection but did not differ in the frequency of H-2 antigens when assayed with antisera against antigens of 5 inbred H-2 haplotypes. The selected RH and SL mice were crossbred with, and backcrossed to, the inbred CBA mice. F1 mice from crosses between RH and CBA were as resistant to reinfection with H. polygyrus as their RH parents. F1 mice from crosses between SL and CBA were more resistant than either of their parents. BC1 mice were either positive or negative for H-2 antigens from RH and SL mice. BC1 mice that were positive for RH H-2 antigens were more resistant to infection than their negative littermates, but they were significantly more susceptible to infection with H. polygyrus than their F1 parents. These results demonstrated that genes within and mapped outside H-2 complex control the level of resistance to H. polygyrus in the selected mice and suggested that selective breeding of mice for resistance fixed the relevant genes in and outside the H-2 complex.

Animals↗
PubMed1997

Methionine aminopeptidase (type 2) is the common target for angiogenesis inhibitors AGM-1470 and ovalicin.

BACKGROUND: Angiogenesis, the formation of new blood vessels, is essential for tumor growth. The inhibition of angiogenesis is therefore emerging as a promising therapy for cancer. Two natural products, fumagillin and ovalicin, were discovered to be potent inhibitors of angiogenesis due to their inhibition of endothelial cell proliferation. An analog of fumagillin, AGM-1470, is currently undergoing clinical trials for the treatment of a variety of cancers. The underlying molecular mechanism of the inhibition of angiogenesis by these natural drugs has remained unknown. RESULTS: Both AGM-1470 and ovalicin bind to a common bifunctional protein, identified by mass spectrometry as the type 2 methionine aminopeptidase (MetAP2). This protein also acts as an inhibitor of eukaryotic initiation factor 2alpha (elF-2alpha) phosphorylation. Both drugs potently inhibit the methionine aminopeptidase activity of MetAP2 without affecting its ability to block elF-2alpha phosphorylation. There are two types of methionine aminopeptidase found in eukaryotes, but only the type 2 enzyme is inhibited by the drugs. A series of analogs of fumagillin and ovalicin were synthesized and their potency for inhibition of endothelial cell proliferation and inhibition of methionine aminopeptidase activity was determined. A significant correlation was found between the two activities. CONCLUSIONS: The protein MetAP2 is a common molecular target for both AGM-1470 and ovalicin. This finding suggests that MetAP2 may play a critical role in the proliferation of endothelial cells and may serve as a promising target for the development of new anti-angiogenic drugs.

Affinity Labels↗
PubMed1997

[Separation of soybean agglutinin by hydrophobic-interaction chromatography].

The soybean agglutinin (SBA) was separated with hydrophobic-interaction chromatography (HIC) in this work. HIC of the crude lectin extract of SBA was performed on Phenyl-Sepharose CL-4B column, 10 cm x 2.5 cm i.d., at a flow-rate of 1.0 mL/min. A 20 mL sample of the crude extract was applied to the column previously equilibrated with the buffer, 0.01 mol/L PBS containing ammonium sulfate (60% of saturation concentration). The column was eluted with the starting buffer, then with the buffer containing 30% saturation of ammonium sulfate, and finally with 0.01 mol/L PBS. Fractions were detected by UV absorbance at 280 nm and assayed for hemagglutinating activity. The results show that the purification-fold was as high as 35 and the recovery of activity was 100%.

Chromatography↗
PubMed1996

Peroxynitrite formation from activated human leukocytes.

We showed direct evidence of peroxynitrite formation from polymorphonuclear cells (PMN) with the nitration of 4-hydroxyphenylacetic acid (HPA) to 4-hydroxy-3-nitrophenylacetic acid (NO2HPA). Human PMN from healthy volunteers was stimulated with phorbol-12-myristate-13-acetate (PMA, 10 ng/ml) at 37 degrees C in 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid-buffered Hank's balanced salt solution (pH 7.4) with HPA (1 mM). NO2HPA was detected under PMA stimulation only in the presence of myeloperoxidase inhibitor. NO2HPA was eliminated by N-monomethyl-L-arginine (100 microM). The inhibition of myeloperoxidase appears to be essential to demonstrate the production of NO2HPA since myeloperoxidase itself or its product, hypochlorite, reacted with peroxynitrite and hampered the formation of NO2HPA.

Animals↗
PubMed1996

Biosynthesis of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine of cyclosporin A: enzymatic analysis of the reaction sequence including identification of the methylation precursor in a polyketide pathway.

3(R)-Hydroxy-4(R)-methyl-6(E)-octenoic acid, the C9-backbone of the unusual amino acid (4R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (Bmt), is biosynthesized as a coenzyme A thioester from acetyl-CoA, malonyl-CoA, NADPH, and S-adenosylmethionine via a polyketide pathway. Here we present detailed enzymatic studies about the basic assembly process. After attachment of the activated building units to Bmt polyketide synthase the intermediates remained enzyme-bound throughout the cycle. Premature cutoff of biosynthesis led to the release of the intermediates from the enzyme, either as coenzyme A thioesters or, in the case of reactive C8-intermediates, as lactones. Enzyme-bound 3-oxo-4-hexenoic acid, the condensation product of the second elongation cycle, could be identified as the exclusive substrate for the introduction of the methyl group. Part of the biosynthesis including the first elongation cycle, the second condensation reaction, and the methylation step was shown to follow a processive mechanism. All activated intermediates of this processive part could be introduced into the correct pathway at the respective steps, whereas 2-methyl-3-oxo-4-hexenoyl-CoA and all following methylated intermediates were not able to enter the cycle any more. Obviously, the region of Bmt polyketide synthase responsible for this latter part of the biosynthetic pathway is inaccessible for externally supplied coenzyme A thioesters. Butyryl-CoA was recognized by Bmt polyketide synthase with an efficiency comparable to that of crotonyl-CoA and processed to 3-hydroxy-4-methyloctanoyl-CoA, the saturated analog of the natural basic assembly product, indicating a relaxed specificity of Bmt polyketide synthase with respect to the starter unit.

Chromatography, Thin Layer↗
PubMed1996

The fourth EF-hand of calmodulin and its helix-loop-helix components: impact on calcium binding and enzyme activation.

CaM (4 cTnC) is a calmodulin--cardiac troponin C chimeric protein containing the first, second, and third calcium-binding EF-hands of calmodulin (CaM) and the fourth EF-hand of cardiac troponin C (cTnC) [George, S.E., Su, Z., Fan, D., & Means, A.R. (1993) J. Biol. Chem. 268, 25213-25220]. CaM (4 cTnC) showed 2-fold-enhanced carboxy-terminal Ca2+ affinity relative to CaM and also exhibited impaired activation of the CaM-regulated enzymes smooth muscle myosin light chain kinase (smMLCK), neuronal nitric oxide synthase (nNOS), and phosphodiesterase (PDE). To investigate the molecular basis for these effects, we constructed (1) additional chimeras, replacing most of CaM helix 7, Ca2+-binding loop 4, and helix 8 with the corresponding helices and loops of cTnC; and (2) point mutants in the fourth EF-hand of CaM. Replacement of CaM's fourth loop with the corresponding loop of cTnC enhanced Ca2+ affinity by over 3-fold through an increase in the Ca2+ on rate and also reduced cooperativity of Ca2+ binding. In contrast, substitution of CaM helix 7 or 8 modestly decreased Ca2+ affinity by increasing the Ca2+ off rate, without impairment of cooperativity. All three of the helix and loop chimeras fully activated PDE, with minor shifts in Kact. CaM (helix 7 cTnC) showed a significantly impaired ability to activate smMLCK and nNOS, whereas the other two chimeras retained about 80% of the maximal smMLCK and nNOS activation observed with CaM.

Calcium↗
PubMed1996

High density lipoproteins increase cytoplasmic free calcium in bovine aortic endothelial cells.

This study examined the influence of human high density lipoproteins (HDL) on the intracellular free calcium of cultured bovine aortic endothelial cells (BAECs). Intracellular Ca2+ concentration ([Ca2+]i) was determined by a fluorescent calcium indicator, Fura-2. It was found that, in the presence of 1 mmol/L extracellular calcium, HDL resulted in a biphasic elevation of [Ca2+]i in BAECs, consisting of an initial, transient component followed by a lower, but more sustained component. Doses of HDL from 25 to 200 micrograms protein/ml induced marked concentration-dependent elevations of [Ca2+]i in BAECs. The sustained component was abolished by deprivation of extracellular calcium or by pretreatment of endothelial cells with a calcium influx blocker, NiCl2, HDL-induced elevation of [Ca2+]i was attenuated in a concentration-dependent way by an inhibitor of calcium release, tetracaine. Repeated applications of HDL (100 micrograms protein/ml) markedly blunted the initial peak component of the calcium transient of BAECs. These results demonstrate that both intracellular and extracellular calcium pools are responsible for the biphasic elevation of [Ca2+]i induced by HDL in cultured BAECs.

Anesthetics, Local↗
PubMed1996

[Studies on Cnidium fruits by stereological method and computer image analysis].

The fruits, pollen grains, vascular bundles, stomata and endosperm cells of 4 Cnidium species were studied and determined by stereological method and computer image analysis technique. Statistical data were presented. In the volume of fruit and the area of vascular bundle, Cnidium dahuricum is the biggest, then C. salinum, C. japonicum and C. monnieri successively. In the volume of pollen grain,C. salinum is the biggest, followed by C. dahuricum, C. japonicum and C. monnieri in succession. In the volume of endosperm cell, C. dahuricum is also the biggest, and then C. japonicum, C. salinum and C. monnieri in order.

Fruit↗
PubMed1996

[Dynamic assay of oleanolic acid in Aralia taibaiensis Z. Z. Wang et H. C. Zheng].

The dynamic assay on oleanolic acid (OA) in Aralia taibaiensis shows that the plant has a higher OA level. The level in root cortex is 4.74%-10.81% and peak stages are mid-May to late June and late August to mid-September the level in stem barks is 3.59%-12.06% and peak period is between mid-May and late July, the level in leaves increases throughout the life time ranging from 2.41% to 6.66% and peak level is 6.66% around mid-September.

Drugs, Chinese Herbal↗
PubMed1996

[A study of HIA-DR antigen expression in nasopharyngeal carcinoma and its relation with clinical pathology and prognosis].

In order to clarify the relationship between HLA-DR antigen expression of nasopharyngeal carcinoma (NPC) and the clinicopathology and prognosis of NPC, immunohistochemical studies on HLA-DR antigen expression in 77 NPC cases were performed. The results showed that the positive rate of HLA-DR was 44.2% in this series. Non-neoplastic epithelium did not express this antigen. A close association was found between expression of HLA-DR antigen and the clinical staging of NPC. The positive rate of HLA-DR gradually decreased with tumor progression, showing a remarkable difference among tumors in different clinical stages (P < 0.05). Analysis of patient survival demonstrated that the prognosis of NPC patients with HLA-DR expression was significantly better than those without (P < 0.01). The above results give support to the possibility of immunomodulation of tumors.

Adult↗
PubMed1996

[The cochlea in short-term culture].

In order to establish organotypic culture of the cochlea, the dissection of the early postnatal mouse cochlea and its morphology in short-term culture were investigated. The viability of hair cells in the culture was assessed using differential interference contrast (DIC) microscopy and double-staining with fluorescein diacetate (FDA) and propidium iodide (PI). The hair cells remained viable and did not show any signs of damage for up to 8-18 hours. When incubated in Hank's solution containing 1 mmol/L dihydrostreptomycin, the hair cells initially deteriorated in 0.5-4.5 hours and progressed to entire degeneration after 10-20 hours. In addition to its utilization in organotypic culture, the cochlea in short-term culture can be used as a valuable model for studying cellular and molecular neurobiology of the inner ears.

Animals↗