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Biomedical subjects

Z Su

Publications and source records attributed to Z Su.

At least 73 records · Page 4Linked to original sources

[Analysis on chemical composition of genus Pueraria stems from China].

OBJECTIVE: To provide scientific basis for developing and utilizing Pueraria stems. METHOD: The contents of total flavonoid were determined by means of UV spectrophotometry. The isoflavones in stems and roots of nine species of genus Pueraria were analyzed by TLC. RESULTS: The stems and roots are similar in chemical composition. CONCLUSION: Pueraria stems as a potential resource could be used as a substitute for Pueraria roots.

Chromatography, Thin Layer↗

[Variations of the middle meatus mucosa ultrastructure after endoscopic sinus surgery].

OBJECTIVE: To explore the variations of middle meatus ultrastructure after endoscopic sinus surgery. METHOD: 10 cases whose middle meatus mucosa recovered well after undergoing endoscopic sinus surgery were screened, and postoperative electron microscope examinations of middle meatus mucosa were made in the first, second, third and forth month. RESULT: In the first month after operation, there was obvious fibre proliferation in the mucosa. In the second month, there was fibre proliferation and dissolution existing simultaneously. In the third month, the mucosa's structure resumed fundamentally to normal, but its function was not perfect. In the forth month, the mucosa was completely normal and can function normally. CONCLUSION: The mucosa of middle meatus can resume completely after endoscopic sinus surgery but need at least four months. It is very important to have a long time reexamination for improving therapeutic effect.

Adult↗

Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2.

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Fumagillin and ovalicin compose a class of structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. A synthetic analog of fumagillin, TNP-470, is currently undergoing clinical trials for treatment of a variety of cancers. A common target for fumagillin and ovalicin recently was identified as the type 2 methionine aminopeptidase (MetAP2). These natural products bind MetAP2 covalently, inhibiting its enzymatic activity. The specificity of this binding is underscored by the lack of inhibition of the closely related type 1 enzyme, MetAP1. The molecular basis of the high affinity and specificity of these inhibitors for MetAP2 has remained undiscovered. To determine the structural elements of these inhibitors and MetAP2 that are involved in this interaction, we synthesized fumagillin analogs in which each of the potentially reactive epoxide groups was removed either individually or in combination. We found that the ring epoxide in fumagillin is involved in the covalent modification of MetAP2, whereas the side chain epoxide group is dispensable. By using a fumagillin analog tagged with fluorescein, His-231 in MetAP2 was identified as the residue that is covalently modified by fumagillin. Site-directed mutagenesis of His-231 demonstrated its importance for the catalytic activity of MetAP2 and confirmed that the same residue is covalently modified by fumagillin. These results, in agreement with a recent structural study, suggest that fumagillin and ovalicin inhibit MetAP2 by irreversible blockage of the active site.

Amino Acid Sequence↗

Effects of overexpression of the Na+-Ca2+ exchanger on [Ca2+]i transients in murine ventricular myocytes.

We measured [Ca2+]i and [Na+]i in isolated transgenic (TG) mouse myocytes overexpressing the Na+-Ca2+ exchanger and in wild-type (WT) myocytes. In TG myocytes, the peak systolic level and amplitude of electrically stimulated (ES) [Ca2+]i transients (0.25 Hz) were not significantly different from those in WT myocytes, but the time to peak [Ca2+]i was significantly prolonged. The decline of ES [Ca2+]i transients was significantly accelerated in TG myocytes. The decline of a long-duration (4-s) caffeine-induced [Ca2+]i transient was markedly faster in TG myocytes, and [Na+]i was identical in TG and WT myocytes, indicating that the overexpressed Na+-Ca2+ exchanger is functionally active. The decline of a short-duration (100-ms) caffeine-induced [Ca2+]i transient in 0 Na+/0 Ca2+ solution did not differ between the two groups, suggesting that the sarcoplasmic reticulum (SR) Ca2+-ATPase function is not altered by overexpression of the Na+-Ca2+ exchanger. There was no difference in L-type Ca2+ current density in WT and TG myocytes. However, the sensitivity of ES [Ca2+]i transients to nifedipine was reduced in TG myocytes. This maintenance of [Ca2+]i transients in nifedipine was inhibited by Ni2+ and required SR Ca2+ content, consistent with enhanced Ca2+ influx by reverse Na+-Ca2+ exchange, and the resulting Ca2+-induced Ca2+ release from SR. The rate of rise of [Ca2+]i transients in nifedipine in TG myocytes was much slower than when both the L-type Ca2+ current and the Na+-Ca2+ exchange current function together. In TG myocytes, action potential amplitude and action potential duration at 50% repolarization were reduced, and action potential duration at 90% repolarization was increased, relative to WT myocytes. These data suggest that under these conditions, overexpression of the Na+-Ca2+ exchanger in TG myocytes accelerates the decline of [Ca2+]i during relaxation, indicating enhanced forward Na+-Ca2+ exchanger function. Increased Ca2+ influx also appears to occur, consistent with enhanced reverse function. These findings provide support for the physiological importance of both these modes of Na+-Ca2+ exchange.

Action Potentials↗

Antisense inhibition of the PTI-1 oncogene reverses cancer phenotypes.

The genetic alterations and molecular events mediating human prostate cancer development and progression remain to be defined. Rapid expression cloning and differential RNA display detect a putative oncogene, prostate tumor-inducing gene 1 (PTI-1), that is differentially expressed in human prostate (as well as breast, colon, and small cell lung) cancer cell lines, patient-derived prostate carcinomas, and blood from patients with metastatic prostate cancer. PTI-1 consists of a unique 5' untranslated region (5' UTR) with significant sequence homology to Mycoplasma hyopneumoniae 23S ribosomal RNA juxtaposed to a sequence that encodes a truncated and mutated human elongation factor 1alpha (Trun-EF). Stable expression of a nearly full-length 1.9-kb PTI-1 gene, but not the separate PTI-1 5' UTR or Trun-EF region, in normal rat embryo fibroblast cells, CREF-Trans 6, induces an aggressive tumorigenic phenotype in athymic nude mice. Blocking PTI-1 expression with antisense PTI-1 results in reversion of transformed PTI-1-expressing cells to a more normal cellular morphology with suppression in both anchorage-independent growth and tumorigenic potential in athymic nude mice. These findings document that PTI-1 is indeed an oncogene, and directly blocking PTI-1 expression can nullify cancer phenotypes. In these contexts, PTI-1 not only represents a gene with discriminating diagnostic properties but also may serve as a target for the gene-based therapy of human prostate and other cancers.

Animals↗

Sarcoplasmic reticulum function in murine ventricular myocytes overexpressing SR CaATPase.

To examine the effects of the overexpression of sarcoplasmic reticulum (SR) CaATPase on function of the SR and Ca2+ homeostasis, we measured [Ca2+]i transients (fluo-3), and L-type Ca2+ currents (ICa.L), Na/Ca exchanger currents (INa/Ca), and SR Ca2+ content with voltage clamp in ventricular myocytes isolated from wild type (WT) mice and transgenic (SRTG) mice. The amplitude of [Ca2+]i transients was insignificantly increased in SRTG myocytes, while the diastolic [Ca2+]i tended to be lower. The initial and terminal declines of [Ca2+]i transients were significantly accelerated in SRTG myocytes, implying a functional upregulation of the SR CaATPase. We examined the functional contribution of only the SR CaATPase to the initial and the terminal phase of the decline of [Ca2+]i, by abruptly inhibiting Na/Ca exchange with a rapid switcher device. The rate of [Ca2+] decline mediated by the SR CaATPase was increased by 40% in SRTG compared with WT myocytes. The function of the L-type Ca2+ channel was unchanged in SRTG myocytes, while INa/Ca density was slightly (10%) decreased. Measured SR Ca2+ content was significantly increased by 29% in SRTG myocytes. Thus, overexpression of SR CaATPase markedly accelerates the decline of [Ca2+]i transients, and induces in increase in SR Ca2+ content, with some downregulation of the Na/Ca exchanger.

Animals↗

Peroxynitrite is not a major mediator of endothelial cell injury by activated neutrophils in vitro.

OBJECTIVE: Human polymorphonuclear leukocytes (PMN) produce nitric oxide (NO), superoxide (O2.-) and peroxynitrite (ONOO-) upon stimulation. We investigated the role of ONOO- in PMN-induced injury to cultured bovine aortic endothelial cells (BAEC). METHODS: BAEC were cocultured with phorbol 12-myristate 13-acetate (PMA)-activated human PMN (effector-to-target ratio, 10:1) and injury to BAEC was evaluated at intervals by 51Cr release assay. The levels of NO, O2.-, ONOO- and nitrotyrosine, a reaction product of ONOO-, were also measured, and the influence of NO synthase inhibitors, O2.- and hydroxyl radical scavengers and other effectors was examined. RESULTS: In BAEC cocultured with PMA-activated PMN, 51Cr release was significantly increased [14.6 +/- 2.2% at 2 h (p < 0.05) and 42.6 +/- 2.7% at 4 h (p < 0.01); control (nonactivated PMN), < 4%]. Superoxide dismutase (100 U/ml) reduced 51Cr release to 4.6 +/- 2.2% at 2 h (p < 0.05). N-Iminoethyl-L-ornithine (L-NIO, 0.1 mM) potentiated 51Cr release (30.6 +/- 3.8% at 2 h, p < 0.01), and the potentiation was eliminated by anti-CD18 monoclonal antibody. The 51Cr release was completely prevented by dimethyl sulfoxide or by deferoxamine. Treatment of PMN with L-NIO inhibited NO generation and increased O2.- production. The nitrotyrosine level did not increase in BAEC cocultured with PMA-activated PMN. CONCLUSION: NO-derived ONOO- is not a major cytotoxic mediator in BAEC injury by activated PMN. NO may have a cytoprotective effect by inhibiting PMN adherence to endothelial cells.

Animals↗

Synthetic analogues of TNP-470 and ovalicin reveal a common molecular basis for inhibition of angiogenesis and immunosuppression.

TNP-470 (1), a synthetic derivative of the natural product fumagillin (2), potently inhibits angiogenesis in vivo and the growth of endothelial cell cultures in vitro. The structurally related natural product ovalicin (3) also inhibits angiogenesis but possesses potent immunosuppressive activity. The recent finding that all three drugs bind and inhibit the same target, methionine aminopeptidase 2 (MetAP2), raised the question of whether TNP-470 is also immunosuppressive and whether inhibition of MetAP2 underlies both activities of ovalicin. To address these questions, we synthesized a series of analogues of TNP-470 and ovalicin and tested them for their abilities to inhibit the proliferation of either endothelial cell or mixed lymphocyte cultures. TNP-470 and its analogues were found to possess both immunosuppressive and anti-angiogenic activities. A strong correlation was observed between the ability of compounds to inhibit bovine and human endothelial cell growth and their ability to inhibit the mouse mixed lymphocyte reaction (MLR), implying that the two activities share a common molecular basis, i.e., inhibition of MetAP2. Interestingly, ovalicin and several other compounds behaved differently in the human MLR than in either the mouse MLR or human endothelial cell proliferation assays, pointing to possible species-specific and cell type-specific differences in the metabolism or uptake of these compounds.

Animals↗

Abnormal myocyte Ca2+ homeostasis in rabbits with pacing-induced heart failure.

To determine whether there are abnormalities in myocyte excitation-contraction coupling and intracellular Ca2+ concentration ([Ca2+]i) homeostasis in pacing-induced heart failure (PF), we measured L-type Ca2+ current (ICa,L) and Na+/Ca2+ exchanger current (INa/Ca) with voltage clamp and measured intracellular Na+ concentration ([Na+]i) and [Ca2+]i with the use of sodium-binding benzofuran isophthalate (SBFI) and fluo 3 in ventricular myocytes isolated from control and paced rabbits. The peak systolic and diastolic levels and the amplitude of electrically stimulated [Ca2+]i transients (0.25 Hz, extracellular Ca2+ concentration = 1.08 mM) were significantly less in PF myocytes. Also, there was prolongation of the times to peak and decline of [Ca2+]i transients. ICa,L density was markedly decreased in PF myocytes. INa/Ca at -40 mV elicited by rapid exposure to 0 Na+ solution with a rapid solution switcher was significantly reduced in PF myocytes, suggesting that the function of the Na+/Ca2+ exchanger is impaired in these myocytes. In PF myocytes the decline of the [Ca2+]i transient when the Na+/Ca2+ exchanger was abruptly disabled was markedly prolonged compared with the decline in control myocytes, consistent with depressed sarcoplasmic reticulum (SR) Ca2+-ATPase function. RNase protection assay showed decreased levels of Na+/Ca2+ exchanger and SR Ca2+-ATPase mRNA in PF hearts, consistent with the function studies. We conclude that the functions of L-type Ca2+ channels, Na+/Ca2+ exchanger, and SR Ca2+-ATPase are impaired in myocytes from rabbit hearts with failure induced by rapid pacing. These abnormalities result in reduced [Ca2+]i transients and systolic and diastolic dysfunction and appear to account for the abnormal ventricular function observed.

Animals↗

Influence of prior Na+ pump activity on pump and Na+/Ca2+ exchange currents in mouse ventricular myocytes.

We examined the dependence of peak Na+ pump and Na+/Ca2+ exchanger currents on prior Na+ pump inhibition induced by exposure to zero extracellular K+ in voltage-clamped adult murine ventricular myocytes. Abrupt activation of the Na+ pump by reexposure of myocytes to extracellular K+ with a rapid solution switcher resulted in the development of a transient peak current at approximately 500 ms, followed by a decline over 1-2 min to a steady-state level. The magnitudes of both the peak Na+ pump current (Ip) and the peak outward Na+/Ca2+ exchange current, activated by rapidly reducing extracellular Na+ to zero with the solution switcher, were dependent on previous Na+ pump activity. [Na+] gradients (Na+-binding benzofuran isophthalate fluorescence) between the patch pipette and the bulk cytosol were relatively small and could not account for the large differences between peak and steady-state Ip and reverse Na+/Ca2+ exchanger currents. Our results are consistent with the presence of a subsarcolemmal Na+ concentration gradient, which is similar for the Na+ pump and the Na+/Ca2+ exchanger. These findings also support the hypothesis that the Na+ pump and the Na+/Ca2+ exchanger are colocalized in the sarcolemma.

Animals↗

Two-kidney, two clip renovascular hypertensive rats can be used as stroke-prone rats.

BACKGROUND AND PURPOSE: The cerebrovascular lesions in stroke-prone spontaneously hypertensive rats are not only dependent on high blood pressure but partly related to pressure-independent genetic factors. The aim of the present study was to observe whether spontaneous stroke occurred in renovascular hypertensive rats without a genetic deficiency. METHODS: The 1-kidney, 1 clip (1k1c); 2-kidney, 1 clip (2k1c); and 2-kidney, 2 clip (2k2c) methods were used to induce hypertension in male Sprague-Dawley rats with a ring-shaped silver clip. Sham-operated rats were used as controls. Blood pressure and neurological symptoms were observed in the rats without any artificial inducement. Brain sections stained with hematoxylin-eosin and phosphotungstic acid-hematoxylin were examined under a microscope to determine stroke foci. RESULTS: The attack rate of stable hypertension was 100% (55/55) in the 2k2c group, which was significantly higher than that in the 1k1c (23/30, 76.7%) and 2k1c (21/30, 70%) groups (P<0.01). None of the rats in the 2k2c group died of acute renal failure or suffered from diffuse cerebral lesions postoperatively. Forty weeks after renal artery constriction, the incidence of spontaneous stroke in the 2k2c group was 61.8% (34/55), which was significant higher than that in the 1k1c (7/30, 23.3%) and 2k1c (5/30,16.7%) groups (P<0.01). Stroke foci were not observed in normotensive controls. CONCLUSIONS: We conclude that 2k2c renovascular hypertensive rats with proper renal artery constriction can be used as stroke-prone renovascular hypertensive rats independent of a genetic deficiency.

Animals↗

Oxygen transfer characteristics in the compact callus aggregates of Rhodiola sachalinensis.

The effective diffusivity of oxygen in compact callus aggregates (CCA) of Rhodiola sachalinensis was extremely small, varying from 0.34 x 10(-11) to 5.4 x 10(-9) m2/s and increasing with particle diameter. The calculated results indicated that severe oxygen limitations occurred in the CCA aggregates. However, the direct determination of the viability of the cells demonstrated that the CCA aggregates contained a high fraction of viable cells. It was suggested that the tissue differentiation or plasmodesmata within the CCA aggregates may provide capillaries for improving transport of oxygen and other nutrients.

Drugs, Chinese Herbal↗

[Observation on inhibitory effect of tetrandrine on the growth of human skin fibroblast in vitro].

The effect of tetrandrine on the growth of human skin fibroblasts was observed in vitro culture. The result revealed that tetrandrine significantly inhibited the growth of fibroblast. The higher the concentration of tetrandrine, the higher the inhibition rate, forming a time-dependent relationship. The possible value of tetrandrine in the treatment of hypertrophic scar is discussed.

Alkaloids↗

Stroke-prone renovascular hypertensive rats.

PURPOSE: To summarized the methods for establishment, characteristics of vascular lesions in brain and heart and the application of stroke-prone renovascular hypertensive rats (RHRSP). DATA SOURCES AND METHODS: Most published original articles about RHRSP in our laboratory were reviewed. RESULTS: After the renal arteries were constricted bilaterally with ring-shape silver clips, the stroke-prone renovascular hypertensive rats were established. Hypertension was produced in all RHRSP (100%). The peak of blood pressure in RHRSP reached 29.1 +/- 3.0 kPa. The lesions of cerebral arteries and arterioles and the damage of cerebral capillary structure by hypertension were observed in the RHRSP. The incidence of spontaneous stroke was 56.4% within 40 weeks after the renal artery constriction. Left ventricular hypertrophy and small coronary arterial lesions in myocardium were discovered in all RHRSP. Myocardial infarction occurred spontaneously in 41.8% of RHRSP. The animal models have been used for the studies on mechanisms of stroke and myocardial infarction. CONCLUSIONS: Because the vascular lesions in cerebrum and heart in RHRSP are similar to that in human beings with hypertension, RHRSP can be used in the studies on mechanisms of hypertensive arteriosclerotic stroke and cardiac lesions and on verifying the effects of different medications to complications of hypertension, and the results might be more reliable than that in animal models without hypertension.

Animals↗

[Physicochemical changes in the process of preparing traditional Chinese drugs].

OBJECTIVE: Summarizing the physicochemical changes in the process of preparing traditional Chinese drugs and affording useful clues for the quality improvement of Chinese patent drugs. METHOD: Introducing the main physicochemical changes, such as precipitating reaction, solubility increasing, hydrolysis, and oxidation-reduction etc., which occur in the process of extracting, separating, concentrating and drying. RESULT AND CONCLUSION: The research of physicochemical changes occurring in the process of preparation and the probe into their mechanism play an important role in perfecting the basic theories of Chinese pharmacy, promoting the development of compatibility theory of Chinese pharmacy and improving the technology design for preparing and controlling the quality of Chinese patent drugs.

Drugs, Chinese Herbal↗

[Diagnostic significance of cuticular patterns on corolla surface from Pueraria spp].

OBJECTIVE: To provide reference materials for the classification and identification of Pueraria spp. by studying the cuticular patterns on corolla surface. METHOD: The cuticular patterns of corolla were observed under SEM (scanning electron microscope). RESULT: The species of the genus Pueraria are defferent from each other in cuticular patterns. CONCLUSION: The diagnostic characters of the cuticular patterns on corolla surface can be used for the classification and identification of Pueraria spp.

Fabaceae↗

[Isolation and observation of ciliated cells from guinea pig's nasal epithelium].

OBJECTIVE: To investigate nasal physiological function at a cellular level and to establish a method for isolating single ciliated cells from guinea pig's nasal epithelium. METHODS: The ciliated cells were isolated by means of mechanical dissociation after papain treatment and a differential interference contrast (DIC) microscope was used for 1000-fold observation (objective lens: 100-fold; eye piece: 10-fold). RESULTS: A total of 12,587 single ciliated cells could be isolated from nasal epithelium of each guinea pig. The criteria for good viability of isolated nasal ciliated cells include: (1) actively motile cilia; (2) a smooth cytoplasmic membrane; (3) cytoplasm in a state of translucence (birefringence); (4) cells neither swollen nor shrunk. With short term culture at room temperature, the isolated nasal ciliated cells retained a good viability for 2-9 hours or longer. The living ciliated cells showed swing motions of cilia with fast and slow phases at a rate of 51-119 times per minute. CONCLUSION: A method for isolating ciliated cells from guinea pig's nasal epithelium and a criteria for good viability of isolated ciliated cells have been established. Ciliary motion pattern and ciliary beating frequency were also studied.

Animals↗