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Biomedical subjects

Z Xia

Publications and source records attributed to Z Xia.

At least 73 records · Page 4Linked to original sources

Hepatic ceroid-lipofuscinosis in enzootic cardiomyopathy of sika deer (Cervus nippon temminck).

Hepatic lesions in 25 sika deer (Cervus nippon Temminck) aged 1-15 days, affected by selenium-deficiency cardiomyopathy, were examined histopathologically. Characteristic pathological findings, induced by stagnation of the plasma proteins of the cytoplasm, consisted of vacuolar degeneration of hepatocytes, formation of hyalin droplets, and ceroid-lipofuscinosis. Electron microscopically, these changes were closely associated with degeneration of the endoplasmic reticulum and mitochondria. Peroxisomes, which were observed around the vacuoles, were regarded as a reactive result of membrane disturbance caused by a decrease in glutathione peroxidase (GSH-Px)

Animals↗

Signaling pathways mediating anti-apoptotic action of neurotrophins.

Neurotrophins promote survival and suppress apoptosis in many populations of neurons. Currently, phosphatidylinositol-3 kinase (PI-3K) is recognized as the main mediator of this protective effect. However, most of the data collected so far on the anti-apoptotic signaling of neurotrophins were obtained using trophic withdrawal paradigms. Recent data from our and other groups indicate that extracellular-signal-regulated kinase 1/2 (Erk 1/2) may play a critical role in suppressing neuronal apoptosis triggered by cellular damage. Thus, it appears that either Erk1/2 or PI-3K, depending on the nature of the death-inducing stimulus, can mediate anti-apoptotic signaling of neurotrophins. In this review, we discuss the contribution of Erk1/2 and PI-3K to neuroprotection by neurotrophins. We also present data suggesting possible mechanisms by which these pathways might suppress neuronal death.

Animals↗

Nuclear volume estimation using different sampling, measurement and calculation methods.

OBJECTIVE: To study the reliability of volume parameter measured on tissue sections through different sampling, measurement and calculation methods. STUDY DESIGN: The largest nuclear profile image under a 100x, NA 1.30 oil immersion objective of primary spermatocytes and spherical spermatoblasts on 11-micron-thick seminiferous tubule sections and tissue images, under a 20x objective, on 4-micron sections were captured. Their volumes were measured and calculated by the five methods provided by the Technology for Image and Graphics Engineering Research cell image analysis system. RESULTS: The nuclear volumes obtained by nucleator and area equivalent diameter on the largest nuclear profile image were almost the same, including binary images by automated and manual interactive nucleator and grey scale images only by the latter. Nuclear volumes, calculated by random Feret diameter and equivalent diameter of the perimeter, the minimal circumference of the largest nuclear profile binary image, were obviously larger than those of the nucleator and area equivalent diameter. Due to different-sized nuclear slices entrapped in the same section, those nuclear volumes from the seminiferous tubule tissue images were strikingly lower than that of the largest nuclei profile image. The shape factors of primary spermatocytes and spherical spermatoblast nuclei under 100x and 20x objectives were approximately the same. CONCLUSION: The sample preparation, sampling methods and calculation formulas suitable to nuclear form are necessary to obtain reproducible volume parameters.

Animals↗

[Research on the parameters of Mark V injector].

This study sought to correctly preset the parameters of Mark v injection. The emphasis was laid on the flow rate in that, it ought to be set more carefully and more accurately for ensuring success in angiography. The authors analyzed the influential factors of flow rate and the relationship between flow rate and pressure limiting and hence proposed a set of typical presetting injection parameters. Experimental results demonstrated that with the contrast media concentration around 75%, high quality images could be obtained by setting the pressure limiting within 2068-5515 kPa.

Coronary Angiography↗

A clinical investigation on garlicin injectio for treatment of unstable angina pectoris and its actions on plasma endothelin and blood sugar levels.

To investigate the therapeutic effects and mechanisms of garlicin for treatment of unstable angina pectoris (UAP), garlicin injectio was intravenously dripped 60 mg/day in 34 cases for 10 days. Nitroglycerine was used in 21 cases of the control group. The results showed that the total effective rates in improving symptoms and electrocardiogram after garlicin treatment were respectively 82% and 62%, and that the plasma endothelin and blood sugar levels were markedly lowered in cases with hyperglycemia.

Aged↗

[Combined treatment of pseudohermaphroditism].

OBJECTIVE: To diagnose and treat female pseudohermaphroditism caused by 21-hydroxylase deficiencies. METHODS: Four female patients with 21-hydroxylase deficiencies have received combined treatment of reconstructive surgery and supplementary glucocorticoid in our hospital since 1990. RESULTS: The patients obtained a female external genitalia through the operation. Various symptoms resulted from 21-hydroxylase deficiency were improved with glucocorticoid therapy. CONCLUSION: A satisfying result can be achieved for pseudohermaphroditism by combination of surgery and medicine.

Adolescent↗

[Myocardial apoptosis induced by delayed fluid resuscitation in a burned rat model].

OBJECTIVE: To explore the possibility and the mechanism of myocardial apoptosis induced by delayed fluid resuscitation in a burned rat model and its relationship with nitric oxide (NO) and oxygen-derived free radicals. METHODS: In a rat model with 30% III degree burn, the genomic DNA of the myocardial tissue was detected with ApoAlert(TMLM)-PCR Ladder Assay Kit and visualized with agarose gel electrophoresis. Meanwhile, the NO and the content of unsaturated fatty acids were measured. RESULTS: In rats receiving delayed fluid resuscitation following burn, the myocardial genomic DNA exhibited DNA ladder-index of apoptosis, and the contents of myocardial NO and unsaturated fatty acid were much lower than those in rats receiving immediate resuscitation (P < 0.05). CONCLUSION: The myocardial tissue undergoes apoptosis in burned rats receiving delayed fluid resuscitation, and the decreased NO and the production of oxygen-derived free radicals are also observed in this process.

Animals↗

[Alterations of anabolism in hepatic cells of burned rats measured by (13)C NMR spectroscopy].

OBJECTIVE: To introduce a safe and specific approach of (13)C NMR spectroscopy and investigate the alterations in hepatic anabolism functions including pyruvate recycling, gluconeogenesis and anaplerosis in severely burned rats. METHODS: Adult Spreque -- Dawley (SD) rats were catheterized arteriovenously via left carotid and right external jugular vein under inhalation anesthesia and were randomly divided into burn group (B) and sham burn group (S). Fluid resuscitation started 20 min postburn. Sodium [1, 2, 3 -- (13)C] propionate (SP) was intravenously administered as a tracer at 72 postburn hour (PBH). (13)C NMR spectroscopy of extracted plasma and liver, arterial blood pressure, heart rate and plasma glucose and sodium levels were measured. Metabolic parameters were calculated using a mathematical model of input -- output matrix to feed the tricarboxylic acid cycle. RESULTS: When compared to those in C group, burned rats exhibited a lower arterial blood pressure, but normal blood glucose at 72 PBH. Intravenous SP infusion did not alter MAP, heart rate and plasma sodium. The form of blood sugar labeled by (13)C isotopomer was in excellent agreement with that from liver. After continuous infusion of SP for 45 mins, SP could reach metabolic steady status. The hepatic cellular gluconeogenesis, anaplerosis and the carbon flow rate in pyruvate recycling significantly increased in B group when comparing to those in C group. But the carbon flow rate in Kreb's cycle decreased relatively, and hepatic pools of alanine, glutamic acid and glutamine were enlarged obviously in burned rats relative to sham burn group. CONCLUSION: These data suggested that intravenous infusion of SP would not alter MAP, heart rate and blood sodium. Forty -- five mins after the intravenous infusion, the tracer could reach metabolic steady status. The form of blood sugar labeled by (13)C could represent that of hepatic sugar. Seventy -- two hours after major burns, there were increased hepatic anaplerosis, gluconeogenesis and pyruvate recycling and a correspondent increased utilization ratio of blood sugar by peripheral tissue.

Animals↗

[Effects of Salvia miltiorrhiza compound injection on serum endothelin, prostaglandin I2/thromboxane A2 ratio alteration following myocardial ischemia-reperfusion in patients undergoing intracardiac surgery].

OBJECTIVE: To investigate the effects of Salvia miltiorrhiza compound injection (SMCI) on serum endothelin (ET), prostaglandin I2(PGI2), thromboxane A2(TXA2), and PGI2/TXA2 ratio following myocardial ischemia-reperfusion in patients undergoing intracardiac surgery. METHODS: Twenty patients, scheduled for selective surgery, were randomly divided into the SMCI group (group A, 10 cases) and the control group (group B, 10 cases). SMCI 200 mg/kg was given intravenously in group A before starting the operation and at the time of rewarming respectively, and equivalent volumes of normal saline were administered to group B. The central venous blood samples were collected to measure the serum concentration of ET, PGI2, TXA2, and PGI2/TXA2 ratio. RESULTS: ET significantly reduced, while PGI2 and TXA2 obviously raised in both groups at the beginning (T1) of extracorporeal cardiopulmonary bypass (CPB) (P < 0.05). After cardiac ischemia-reperfusion, ET in group B increased rapidly and significantly (P < 0.05) and evidently higher than the corresponding value in group A 30 min after reperfusion (T3) till 24 hrs after reperfusion (T5). During reperfusion, PGI2 and TXA2 in group A decreased more rapidly than that of group B, while group A maintained higher PGI2/TXA2 ratio than that of group B. At T5, PGI2 and TXA2 in group A were significantly lower than those in group B, while PGI2/TXA2 ratio was higher than that in group B (P < 0.05). The serum ET level was obviously negatively correlated to PGI2/TXA2 ratio. The postoperative cardiac function recovered much better in group A than in that group B. CONCLUSION: SMCI can significantly reduce serum ET level, raise PGI2/TXA2 ratio, thus facilitate the postoperative cardiac function recovery following intracardiac surgery under CPB.

6-Ketoprostaglandin F1 alpha↗

1H NMR investigation of the distal hydrogen bonding network and ligand tilt in the cyanomet complex of oxygen-avid Ascaris suum hemoglobin.

The O(2)-avid hemoglobin from the parasitic nematode Ascaris suum exhibits one of the slowest known O(2) off rates. Solution (1)H NMR has been used to investigate the electronic and molecular structural properties of the active site for the cyano-met derivative of the recombinant first domain of this protein. Assignment of the heme, axial His, and majority of the residues in contact with the heme reveals a molecular structure that is the same as reported in the A. suum HbO(2) crystal structure (Yang, J., Kloek, A., Goldberg, D. E., and Mathews, F. S. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 4224-4228) with the exception that the heme in solution is rotated by 180 degrees about the alpha,gamma-meso axis relative to that in the crystal. The observed dipolar shifts, together with the crystal coordinates of HbO(2), provide the orientation of the magnetic axes in the molecular framework. The major magnetic axis, which correlates with the Fe-CN vector, is found oriented approximately 30 degrees away from the heme normal and indicates significant steric tilt because of interaction with Tyr(30)(B10). The three side chain labile protons for the distal residues Tyr(30)(B10) and Gln(64)(E7) were identified, and their relaxation, dipolar shifts, and nuclear Overhauser effects to adjacent residues used to place them in the distal pocket. It is shown that these two distal residues exhibit the same orientations ideal for H bonding to the ligand and to each other, as found in the A. suum HbO(2) crystal. It is concluded that the ligated cyanide participates in the same distal H bonding network as ligated O(2). The combination of the strong steric tilt of the bound cyanide and slow ring reorientation of the Tyr(30)(B10) side chain supports a crowded and constrained distal pocket.

Animals↗

Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.

Apoptosis is a form of programmed cell death that plays a pivotal role during development and in the homeostasis of the adult nervous systems. However, mechanisms that regulate neuronal apoptosis are not well defined. Here, we report that brain-derived neurotrophic factor (BDNF) protects cortical neurons against apoptosis induced by camptothecin or serum deprivation and activates the extracellular-signal-regulated kinase (ERK) and the phosphatidylinositol 3-kinase (PI 3-kinase) pathways. Using pharmacological agents and transient transfection with dominant interfering or constitutive active components of the ERK or the PI 3-kinase pathway, we demonstrate that the ERK pathway plays a major role in BDNF neuroprotection against camptothecin. Furthermore, ERK is activated in cortical neurons during camptothecin-induced apoptosis, and inhibition of ERK increases apoptosis. In contrast, the PI 3-kinase pathway is the dominant survival mechanism for serum-dependent survival under normal culture conditions and for BDNF protection against serum withdrawal. These results suggest that the ERK pathway is one of several neuroprotective mechanisms that are activated by stress to counteract death signals in central nervous system neurons. Furthermore, the relative contribution of the ERK and PI 3-kinase pathways to neuronal survival may depend on the type of cellular injury.

Animals↗

Changes in the generation of reactive oxygen species and in mitochondrial membrane potential during apoptosis induced by the antidepressants imipramine, clomipramine, and citalopram and the effects on these changes by Bcl-2 and Bcl-X(L).

In order to investigate the molecular mechanism of the antineoplastic effects exerted by the antidepressive agents imipramine, clomipramine, and citalopram, we examined the effects of these compounds on cell viability, generation of reactive oxygen species (ROS), and mitochondrial membrane potential (DeltaPsi(m)) in human acute myeloid leukemia HL-60 cells. Our results indicate that exposure to these compounds causes a loss in cell viability by activating the apoptotic process, as identified by electron microscopy, DNA gel electrophoresis, and flow cytometry. The increased generation of ROS induced by these drugs was a relatively early event and preceded the loss of DeltaPsi(m). Overexpression of the antiapoptotic protein Bcl-2 or Bcl-X(L) prevents antidepressant-induced apoptosis, as well as loss of DeltaPsi(m), but does not affect the generation of ROS.

Antidepressive Agents↗

TL1, a novel tumor necrosis factor-like cytokine, induces apoptosis in endothelial cells. Involvement of activation of stress protein kinases (stress-activated protein kinase and p38 mitogen-activated protein kinase) and caspase-3-like protease.

TL1 is a recently discovered novel member of the tumor necrosis factor (TNF) cytokine family. TL1 is abundantly expressed in endothelial cells, but its function is not known. The present study was undertaken to explore whether TL1 induces apoptosis in endothelial cells and, if so, to explore its mechanism of action. Cultured bovine pulmonary artery endothelial cells (BPAEC) exposed to TL1 showed morphological (including ultrastructural) and biochemical features characteristic of apoptosis. TL1-induced apoptosis in BPAEC was a time- and concentration-dependent process (EC50 = 72 ng/ml). The effect of TL1 was not inhibited by soluble TNF receptors 1 or 2. TL1 up-regulated Fas expression in BPAEC at 8 and 24 h after treatment, and significantly activated stress-activated protein kinase (SAPK) and p38 mitogen-activated protein kinase (p38 MAPK). The peak activities of SAPK and p38 MAPK in TL1-treated BPAEC were increased by 9- and 4-fold, respectively. TL1-induced apoptosis in the BPAEC was reduced by expression of a dominant-interfering mutant of c-Jun (62.8%, p < 0.05) or by a specific p38 inhibitor, SB203580 (1-10 microM) dose-dependently. TL1 also activated caspases in BPAEC, and TL1-induced apoptosis in BPAEC was significantly attenuated by the caspase inhibitor, ZVAD-fluromethyl-ketone. The major component activated by TL1 in BPAEC was caspase-3, which was based on substrate specificity and immunocytochemical analysis. These findings suggest that TL1 may act as an autocrine factor to induce apoptosis in endothelial cells via activation of multiple signaling pathways, including stress protein kinases as well as certain caspases.

Animals↗

The antidepressants imipramine, clomipramine, and citalopram induce apoptosis in human acute myeloid leukemia HL-60 cells via caspase-3 activation.

Some widely used antidepressants such as imipramine, clomipramine, and citalopram have been found to possess antineoplastic effects. In the present study, these compounds were found to induce apoptotic cell death in human acute myeloid leukemia HL-60 cells. Apoptosis induced by the antidepressants was identified by electron microscopy and conventional agarose gel electrophoresis and was quantitated by propodium iodide staining and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) via flow cytometry. Treatment with apoptosis-inducing concentrations of the antidepressants (80 microM imipramine, 35 microM clomipramine, or 220 microM citalopram) caused induction of caspase-3/caspase-3-like activity, which was monitored by the cleavage of poly(ADP-ribose) polymerase (PARP), the loss of the 32 kD caspase-3 (CPP32) precursor, and the cleavage of the fluorescent CPP32-like substrate PhiPhiLux. Pretreatment with a potent caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl-ketone (zVAD-fmk) inhibited antidepressant-induced CPP32/CPP32-like activity and apoptosis. Furthermore, activation of caspase induced by the antidepressants was preceded by the hypergeneration of intracellular reactive oxygen species (ROS). These results suggested that the antidepressants may induce apoptosis via a caspase-3-dependent pathway, and induction of apoptosis by the antidepressants may provide a clue for the mechanism of their antineoplastic effects.

Antidepressive Agents↗

Synthesis and biological evaluation of butanoate, retinoate, and bis(2,2,2-trichloroethyl)phosphate derivatives of 5-fluoro-2'-deoxyuridine and 2',5-difluoro-2'-deoxyuridine as potential dual action anticancer prodrugs.

A group of 3'-O-butanoyl, 5'-O-butanoyl, and 3',5'-di-O-butanoyl esters of 5-fluoro-2'-deoxyuridine (FDU), and 2',5-difluoro-2'-deoxyuridine (DFDU), 3'-O-retinoyl, and 3',5'-di-O-retinoyl esters of FDU, and 5'-O-bis(2,2,2-trichloroethyl)phosphoryl-FDU and its 3'-O-butanoyl ester, was synthesized. These compounds were designed to act as double prodrugs that would serve as a depot to release two active drugs that act through different mechanisms. Thus, a nucleotide derivative of FDU or DFDU could act as a competitive inhibitor for thymidylate synthase, whereas retinoic acid and butyric acid would be expected to induce cell differentiation. The in vitro anticancer activities for these prodrugs were determined against a panel of nine tumor types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate, breast) that encompassed about 60 human tumor cell lines. Structure-activity relationships indicate that O-butanoyl esters of FDU are approximately equipotent to FDU, the O-butanoyl esters of DFDU are less active than FDU, and the retinoyl and bis(2,2,2-trichloroethyl)phosphate derivatives of FDU exhibit comparable activity to FDU. In addition to their cytotoxic effect, 3'-O-retinoyl-FDU (12) and 3'-O-butanoyl-5'-O-bis(2,2,2-trichloroethyl)phosphoryl-FD U (16) also induced in vitro cell differentiation of promyelocytic leukemia HL60 cells. These combined cytotoxic and cell differentiation effects exhibited by 12 and 16 produced greater morphological drug-induced granulation and neutrophil vacuolation, and more cell apoptosis, than observed upon exposure to either retinoic acid or sodium butanoate. Dose-escalation studies in mice showed that 12 or 16 did not induce any acute or chronic toxicity, change in plasma clinical chemistry parameters, or gross histapathological changes at 60 days following an initial dosage regimen of 0.013 mmol/kg i.p. for 7-consecutive days. The in vivo growth delay response of murine mammary EMT6 solid tumors suggests that 3'-O-retinoyl-FDU (12) delays tumor growth relative to the other prodrugs investigated, sodium butyrate, retinoic acid, FDU, or a combination of retinoic acid and FDU. These preliminary results suggest that 3'-O-retinoyl-FDU (12) warrants further in vivo investigation to determine its tissue biodistribution and pharmacokinetic parameters that would be of value in assessing its potential usefulness as an anticancer prodrug.

Animals↗

Cloning, in vitro expression, and novel phylogenetic classification of a channel catfish estrogen receptor.

We obtained two channel catfish estrogen receptor (ccER) cDNA from liver of female fish using RT-PCR. The two fragments were identical in sequence except that the smaller one had an out-of-frame deletion in the E domain, suggesting the existence of ccER splice variants. The larger fragment was used to screen a cDNA library from liver of a prepubescent female. A cDNA was obtained that encoded a 581-amino-acid ER with a deduced molecular weight of 63.8 kDa. Extracts of COS-7 cells transfected with ccER cDNA bound estrogen with high affinity (Kd = 4.7 nM) and specificity. Maximum parsimony and Neighbor Joining analyses were used to generate a phylogenetic classification of ccER on the basis of 18 full-length ER sequences. The tree suggested the existence of two major ER branches. One branch contained two clearly divergent clades which included all piscine ER (except Japanese eel ER) and all tetrapod ERalpha, respectively. The second major branch contained the eel ER and the mammalian ERbeta. The high degree of divergence between the eel ER and mammalian ERbeta suggested that they also represent distinct piscine and tetrapod ER. These data suggest that ERalpha and ERbeta are present throughout vertebrates and that these two major ER types evolved by duplication of an ancestral ER gene. Sequence alignments with other members of the nuclear hormone receptor superfamily indicated the presence of 8 amino acids in the E domain that align exclusively among ER. Four of these amino acids have not received prior research attention and their function is unknown. The novel finding of putative ER splice variants in a nonmammalian vertebrate and the novel phylogenetic classification of ER offer new perspectives in understanding the diversification and function of ER.

Amino Acid Sequence↗

Pregnancy after tubal sterilization with bipolar electrocoagulation. U.S. Collaborative Review of Sterilization Working Group.

OBJECTIVE: To determine risk factors for pregnancy after tubal sterilization with bipolar electrocoagulation. METHODS: A total of 2267 women who had bipolar electrocoagulation were followed for up to 8 to 14 years as part of a multicenter, prospective, cohort study conducted in medical centers in nine United States cities. We used proportional hazards analysis and cumulative life-table probabilities to assess pregnancy risk in these women. RESULTS: The 5-year cumulative probability of pregnancy for women sterilized in 1978-1982 was 19.5 per 1000 procedures (95% confidence interval [CI], 12.2, 26.9); the comparable probability for women sterilized in 1985-1987 was significantly lower, 6.3 per 1000 procedures (95% CI, 0.0, 13.5) (one-tailed P = .01). Women enrolled in 1985-1987 who had fewer than three sites of coagulation had a probability of failure of 12.9 per 1000 procedures (95% CI, 0.0, 38.0); by contrast, women who had three or more sites coagulated had a probability of failure of 3.2 per 1000 procedures (95% CI, 0.0, 9.6) (one-tailed P = .01). CONCLUSION: The long-term probability of pregnancy after tubal sterilization with bipolar coagulation was very low when three or more sites of the fallopian tube were coagulated. Bipolar coagulating systems can be highly effective for sterilization when the fallopian tube is coagulated adequately.

Adolescent↗

Trends in prostatectomy for benign prostatic hyperplasia among black and white men in the United States: 1980 to 1994.

OBJECTIVES: To estimate the annual rate of discharge for prostatectomy for benign prostatic hyperplasia (BPH) in black and white men from 1980 to 1994 using the National Hospital Discharge Survey. METHODS: Overall and race-, age-, and year-specific utilization rates were estimated for the civilian population in the United States. Length of stay was calculated for each discharge, and the results were plotted over time. An expected number of discharges based on the rates observed in 1980 was estimated to determine the impact of decreased prostatectomy rates on the number of procedures that would have been expected in this aging population. RESULTS: Discharge rates for whites were within a narrow range (233.2 to 274.5 per 100,000) from 1980 through 1990 and then displayed a monotonic decline after 1991 to 131.3 per 100,000 in 1994. Rates for blacks were 10% to 24% lower from 1980 to 1991; the decline in discharge rates began in 1993 for blacks, and by 1994 the racial gap had closed. Length of stay decreased throughout the period but length of stay averaged 30% longer for blacks throughout. On the basis of the observed rates of 1980, there were more than 140,000 fewer prostatectomies performed for BPH in 1994 than would have been expected owing to the aging of the population. CONCLUSIONS: These data demonstrate that the black/white differences in prostatectomy for BPH that were observed in the 1980s have disappeared in recent years. Furthermore, rates have declined dramatically in all age- and race-specific groups. Further work is needed to determine whether this convergence in discharge rates is due to equalization of access to medical care or to differences in utilization of alternative therapies.

Black or African American↗