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Biomedical subjects

Z H Zhou

Publications and source records attributed to Z H Zhou.

At least 37 records · Page 2Linked to original sources
PubMed2001

Hyperactive ENaC identifies hypertensive individuals amenable to amiloride therapy.

Pathophysiological features of both primary aldosteronism and pseudohyperaldosteronism are hyperactive amiloride-sensitive epithelial Na(+) channels (ENaC) and refractory hypertension. Peripheral blood lymphocytes express ENaC, which functions and is regulated similarly to ENaC expressed by renal principal cells. Thus it was hypothesized that individuals with either of these hypertensive etiologies could be identified by assessment of the function and regulation of peripheral blood lymphocyte ENaC, by whole cell patch clamp. We also tested the hypothesis that specific inhibition of hyperactive ENaC with amiloride could ameliorate the hypertension. To test these hypotheses, we solicited blood samples from normotensive, controlled hypertensive, and refractory hypertensive individuals. Lymphocytes were examined electrophysiologically to determine whether ENaC was hyperactive. All positive findings were from refractory hypertensive individuals. Nine refractory hypertensive patients had amiloride added to their hypertensive therapy. Amiloride normalized the blood pressure of four subjects. These individuals all had hyperactive ENaC. Amiloride had no effect on individuals with normal ENaC. These findings suggest that whole-cell patch clamp of peripheral blood lymphocytes can be used to identify accurately and rapidly hypertensive individuals who will respond to amiloride therapy.

Adrenal Gland Neoplasms↗
PubMed2001

Stealth polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers: pharmacokinetics and anti-tumor effects.

The objective of this study was to investigate the pharmacokinetics and in vivo anti-tumor effect of recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) encapsulated in poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEG-PHDCA) nanoparticles. Our experimental results showed that PEG-PHDCA nanoparticles could extend the half-life of rHuTNF-alpha to 7.42 h and obviously change the protein biodistribution in tissues, and in particular, increase accumulation of rHuTNF-alpha in tumor. Compared with PHDCA nanoparticles and free rHuTNF-alpha, PEG-PHDCA nanoparticles loaded with rHuTNF-alpha showed higher antitumor potency at the same dose, which might be related to its higher accumulation in tumor tissues and longer plasma circulation time. Therefore, PEG-PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha.

Animals↗
PubMed2001

PEGylated recombinant human tumor necrosis factor alpha: pharmacokinetics and anti-tumor effects.

The aim of the present work was to investigate and assess the merit of PEGylated recombinant human tumor necrosis factor-alpha (rHuTNF-alpha) following our previous work. The rHuTNF-alpha was modified using activated polyethylene glycol (PEG), N-succinimidyl succinnate monomethoxy polyethylene glycol (SS-PEG). The pharmacokinetics and anti-tumor effect were investigated. The experimental results showed that PEGylated rHuTNF-alpha could obviously alter in vivo behavioral characteristics of rHuTNF-alpha. Among the synthesized PEG-rHuTNF-alphas with different PEG molecules, PEG20000-rHuTNF-alpha demonstrated the longest circulating half-life (24.8 h) which was about 50 times longer than that of rHuTNF-alpha (28.8 min). In addition, there was much more PEG20000-rHuTNF-alpha distributed into tumor tissues than other PEG-rHuTNF-alphas or rHuTNF-alpha with time, and PEG20000-rHuTNF-alpha also showed the highest anti-tumor potency. These results indicated that PEG20000-rHuTNF-alpha was a useful long circulating molecule with selective localization in tumor tissues and enhanced anti-tumor activity of rHuTNF-alpha.

Animals↗
PubMed2001

Involvement of calcitonin gene-related peptide in nitroglycerin induced improvement of preservation with cardioplegic solution.

AIM: To study improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of calcitonin gene-related peptide (CG RP) release. METHODS: The isolated rat heart was arrested using St Thomas Hospital cardioplegic solution and then was reperfused with normothermic Krebs-Henseleit solution for 40 min after the 4-h hypothermic ischemic period. Hear t rate, coronary flow, left ventricular pressure (LVP), and its first derivative (+/- dp/dtmax) were recorded, and the calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and the release of creatine kinase (CK) were measured. RESULTS: Nitroglycerin (0.1 or 1 micro;mol/L) or CGRP (5 or 10 nmol/L) caused an improvement of cardiac function (LVP and +/- dp/dtmax) and a decrease in the release of creatine kinase during reperfusion. The protection induced by nitroglycerin was abolished by CGRP(8-37), the selective CGRP receptor antagonist, or pretreatment wit h capsaicin to deplete sensory nerves neurotransmitter content, but was unaltered by treatment w ith glibenclamide, the blocker of the ATP-sensitive potassium channel (KATP). The protection induced by exogenous CGRP was not also blocked by glibenclamide. Levels of CGRP-LI in the coronary effluent were significantly increased in the hearts treated with nitroglycerin. However, the elevated level of CGRP-LI by nitroglycerin was abolished by pretreatment with capsaicin. CONCLUSION: The improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of CGRP release in the rat heart, and the effect is not related to the activation of the KATP channel.

Animals↗
PubMed2001

PEGylated polycyanoacrylate nanoparticles as salvicine carriers: synthesis, preparation, and in vitro characterization.

AIM: To synthesized poly(methoxypolyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEGylated PHDCA) with polyethylene glycol (PEG, Mr = 5000), prepare PEGylated PHDCA and poly(n-hexadecyl cyanoacrylate) (PHDCA) nanoparticles loading salvicine and determine their in vitro characterizations. METHODS: The structure of PEGylated PHDCA was determined with 1H-NMR, 13C-NMR and Fourier transform infrared spectrum (FTIR). Its molecular weight was determined by gel permeation chromatography (GPC). Nanoparticles were prepared by emulsion/solvent evaporation method. RESULTS: 1H-NMR, 13C-NMR, and FTIR were consistent with structure of PEGylated PHDCA, whose average molecular weight is 6680. Entrapment efficiency could be determined by high pressure liquid chromatography (HPLC) method without endogenous interference at the retention time of salvicine. The entrapment efficiency was 92.6 % for PEGylated PHDCA nanoparticles and 98.9 % for PHDCA nanoparticles. The nanoparticles size was about 250 nm. The values of the zeta potential were obviously influenced by the composition of the copolymer. Compared with PHDCA nanoparticles (-23.1 mV), PEGylated PHDCA nanoparticles showed a low surface potential (-9.6 mV). Salvicine release from nanoparticles showed an initial burst effect, then a plateau for an extended period, and finally sustained release phase. CONCLUSION: These results showed that the PEGylated PHDCA nanoparticles could be an effective carrier for salvicine delivery in the respect of anti-tumor potency.

Cyanoacrylates↗
PubMed2001

[Cochinchinenin--a new chalcone dimer from the Chinese dragon blood].

AIM: To study the active constituents of Dracaena cochinchinensis (Lour.) S.C. Chen. in the commercial dragon blood. METHODS: Various column chromatographies with Sephadex L-20 gel, MCI gel and silica gel were employed for the isolation and purification. The structures of compounds were elucidated by spectral analysis. RESULTS: Nine chalcones were isolated from the commercial dragon's blood which was made of D. cochinchinensis (Lour.) S.C. Chen.. By means of spectral data, they were identified as 1-[5-(2,4,4'-trihydroxydihydrochalconyl)]-1- (p-hydroxyphenyl)-3-(2-methoxy-4-hydroxy-phenyl)-propane (1), 2'-methoxysocotrin-5'-ol (2), socotrin-4'-ol (3), 2-methoxy-4, 4'-dihydroxydihydrochalcone (4), 2, 4, 4'-trihydroxy-dihydrochalcone (5), 2, 4, 4'-trihydroxy-6-methoxydihydrochalcone (6), 2', 4', 4-trihydroxychalcone (7), 2-methoxy-4, 4'-dihydroxychalcone (8) and 2'-methoxy-4', 4-dihydroxychalcone (9). CONCLUSION: Compound 1 is a new chalcone dimer and named as cochinchinenin. Compounds 2-9 were isolated from D. cochinchinensis (Lour.) S.C. Chen. for the first time.

Chalcone↗
PubMed2000

Seeing the herpesvirus capsid at 8.5 A.

Human herpesviruses are large and structurally complex viruses that cause a variety of diseases. The three-dimensional structure of the herpesvirus capsid has been determined at 8.5 angstrom resolution by electron cryomicroscopy. More than 30 putative alpha helices were identified in the four proteins that make up the 0.2 billion-dalton shell. Some of these helices are located at domains that undergo conformational changes during capsid assembly and DNA packaging. The unique spatial arrangement of the heterotrimer at the local threefold positions accounts for the asymmetric interactions with adjacent capsid components and the unusual co-dependent folding of its subunits.

Capsid↗
PubMed2000

[Effects of different loading exercises on endogenous sex hormones and their metabolites].

Small loading and strengthening exercises were performed by 22 athletes(11 males and 11 females). The levels of serum hormones and their urinary metabolites were detected. The results showed that the serum levels of testosterone(T), free testosterone(FT) and 17-OH-progesterone(17-OHP) in male athletes exhibited no conspicuous changes. The excretion of their urinary androsteroids was significantly increased after exercises(P < 0.05), but significantly decreased in the recovery period(P < 0.05). After small loading exercises, their serum levels of T and FT revealed no obvious changes except those of 17-OHP which evidently increased in female athletes(P < 0.05); whereas the excretion of their urinary steroid hormones declined promptly after the exercises and in the recovery period (all P < 0.05). After strengthening exercises, the serum levels of T, FT and 17-OHP decreased distinctly in female athletes (all P < 0.05), the excretion of their urinary steroid hormones raised clearly after training and in the recovery period(P < 0.05). Therefore, it is suggested that the secretion and metabolism of sex hormones in the organism are influenced by the loading quality of sports during training, and sexual difference exists simultaneously.

17-alpha-Hydroxyprogesterone↗
PubMed2000

Syntheses and spectroscopic and structural characterization of molybdenum(VI) citrato monomeric raceme and dimer, K4[MoO3(cit)].2H2O and K4[(MoO2)2O(Hcit)2].4H2O.

Investigation of the aqueous coordination chemistry for citrate and molybdenum(VI) resulted in the isolation of molybdenum(VI) citrato monomeric raceme and dimer K4[MoO3(cit)].2H2O (1) and K4[(MoO2)2O(Hcit)2].4H2O (2) (H4cit = citric acid). Complex 1 can serve as the first structurally characterized monomeric citrato molybdate and may represent an early mobilized precursor in the biosynthesis of FeMo-co (FeMo-cofactor). The two complexes have been characterized by elemental analyses and IR and NMR spectroscopies. The IR and NMR spectra are consistent with a monomeric species or a monooxo-bridged dinuclear structure, as revealed by a single crystal X-ray diffraction study. Compound 1 is monoclinic space group P2(1)/c with a = 7.225(1) A, b = 9.151(2) A, c = 22.727(2) A, beta = 94.93(1) degrees, V = 1497.1(7) A3, and Z = 4. Full-matrix least-squares refinement resulted in residuals of R = 0.027 and Rw = 0.032. The molybdenum atom forms an octahedral coordination with three oxo groups and one tridentate citrate, in which the latter is coordinated through the alkoxy and vicinal carboxyl and much more weakly by one of the two terminal groups [2.411(3) A]. Compound 2 is triclinic space group P1 with a = 8.2728(8) A, b = 8.9514(8) A, c = 10.0605(9) A, alpha = 101.673(8) degrees, beta = 100.672(7) degrees, gamma = 112.938(7) degrees, V = 642.5(3) A3, and Z = 1. Full-matrix least-squares refinement resulted in residuals of R = 0.033 and Rw = 0.039. The complex anion contains a linear (O2Mo)O(MoO2) core with the bridging oxo group lying at the center of inversion symmetry (Mo-Ob-Mo, 180 degrees). Each citrate ligand is three-coordinated to one molybdenum atom through the deprotonated hydroxy, alpha-carboxyl, and one beta-carboxyl group, making each metal atom six-coordinate.

Journal Article↗
PubMed2000

Three-dimensional structure of the human herpesvirus 8 capsid.

Human herpesvirus 8 (HHV-8), or Kaposi's sarcoma-associated herpesvirus, is a gammaherpesvirus implicated in all forms of Kaposi's sarcoma and certain lymphomas. HHV-8 has been extensively characterized, both biochemically and immunologically, since its first description in 1994. However, its three-dimensional (3D) structure remained heretofore undetermined largely due to difficulties in viral purification. We have used log-phase cultures of body cavity-based lymphoma 1 cells induced with 12-O-tetradecanoylphorbol-13-acetate to obtain HHV-8 capsids for electron cryomicroscopy and computer reconstruction. The 3D structure of the HHV-8 capsids revealed a capsid shell composed of 12 pentons, 150 hexons, and 320 triplexes arranged on a T=16 icosahedral lattice. This structure is similar to those of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV), which are prototypical members of alpha- and betaherpesviruses, respectively. The inner radius of the HHV-8 capsid is identical to that of the HSV-1 capsid but is smaller than that of the HCMV capsid, which is consistent with the relative sizes of the genomes they enclose. While the HHV-8 capsid exhibits many structural similarities to the HSV-1 capsid, our reconstruction shows two major differences: its hexons lack the "horn-shaped" VP26 densities bound to the HSV-1 hexon subunits, and the HHV-8 triplexes appear smaller and less elongated than those of HSV-1. These differences are in excellent agreement with our sequence comparisons of HHV-8 and HSV-1 capsid proteins. This gammaherpesvirus capsid structure complements previous structural studies on alpha- and betaherpesviruses in providing an account of structural similarities and differences among capsids representing all human herpesvirus subfamilies.

Capsid↗
PubMed2000

gp120-induced alterations of human astrocyte function: Na(+)/H(+) exchange, K(+) conductance, and glutamate flux.

Many human immunodeficiency virus (HIV)-infected patients suffer from impaired neurological function and dementia. This facet of the disease has been termed acquired immunodeficiency syndrome (AIDS)-associated dementia complex (ADC). Several cell types, including astrocytes and neurons, are not productively infected by virus but are involved in ADC pathophysiology. Previous studies of rat astrocytes showed that an HIV coat protein (gp120) accelerated astrocyte Na(+)/H(+) exchange and that the resultant intracellular alkalinization activated a pH-sensitive K(+) conductance. The present experiments were conducted to determine whether gp120 affected human astrocytes in the same fashion. It was found that primary human astrocytes express a pH-sensitive K(+) conductance that was activated on intracellular alkalinization. Also, gp120 treatment of whole cell clamped human astrocytes activated this conductance specifically. Furthermore, gp120 inhibited glutamate uptake by primary human astrocytes. These altered physiological processes could contribute to pathophysiological changes in HIV-infected brains. Because the gp120-induced cell physiological changes were partially inhibited by dimethylamiloride (an inhibitor of Na(+)/H(+) exchange), our findings suggest that modification of human astrocyte Na(+)/H(+) exchange activity may provide a means of addressing some of the neurological complications of HIV infection.

Amiloride↗
PubMed2000

Prevention of rabbit acute lung injury by surfactant, inhaled nitric oxide, and pressure support ventilation.

Improvement of pulmonary perfusion and blood oxygenation and prevention of acute lung injury (ALI) may rely on ventilation strategy. We hypothesized that application of a combined surfactant, inhaled nitric oxide (iNO), and pressure support ventilation (PSV) should more effectively protect the lungs from injury. Anesthetized and intubated adult rabbits weighing 2.8 +/- 0.3 kg were allowed to breathe room air while receiving oleic acid intravenously (60 microl/kg). Within 90 min this caused a reduction of Pa(O(2)) from 94 +/- 7 to 48 +/- 3 mm Hg and dynamic lung compliance (Cdyn) from 1.59 +/- 0.22 to 0.85 +/- 0.10 ml/cm H(2)O/kg (both p < 0.01), and increase of intrapulmonary shunting (Q S/Q T) from 9.4 +/- 1.2 to 27 +/- 5% (p < 0.05). PSV was subsequently applied with 3 cm H(2)O of continuous positive airway pressure and FI(O(2)) of 0.3, and the animals were randomly allocated to four groups, receiving: (1) PSV only (Control, n = 10); (2) iNO at 20 ppm (NO, n = 9); (3) surfactant phospholipids at 100 mg/kg (Surf, n = 8); and (4) surfactant at 100 mg/kg and iNO at 20 ppm (SNO, n = 8). PSV level was varied to maintain a tidal volume of 8 to 10 ml/kg for another 12 h or until early animal death. Five animals in the SNO, three each in the NO and Surf group, and one in the Control group survived 12 h (SNO versus Control, p < 0.05). The NO, Surf, and SNO groups had significantly improved mean Pa(O(2)) (> 70 mm Hg, p < 0.05), and reduced Q S/Q T (15, 19, and 17%, respectively, p < 0.05) at 6 and 12 h, but not in the Control group. The SNO group had the highest values of Cdyn at 12 h, alveolar aeration and disaturated phosphatidylcholine-to-total protein ratio in bronchoalveolar lavage fluid, and the lowest wet-to-dry lung weight ratio and lung injury score (p < 0.05). The results indicate that early alleviation of ALI by surfactant, iNO, and PSV is due to synergistic effects, and only PSV in this model had limited effects.

Administration, Inhalation↗
PubMed1999

A mouse homolog of the Saccharomyces cerevisiae meiotic recombination DNA transesterase Spo11p.

The Saccharomyces cerevisiae Spo11 protein is thought to catalyze formation of the DNA double-strand breaks that initiate meiotic recombination. We have cloned cDNA and genomic DNA for a mouse gene encoding a protein with significant sequence similarity to conserved domains found in proteins of the Spo11p family. This putative mouse Spo11 gene maps to the distal region of chromosome 2 (homologous to human chromosome 20q13.2-q13.3) and comprises at least 12 exons, spanning approximately 15-18 kb. Strong expression of the Spo11 message is seen in juvenile and adult testis by RNA in situ hybridization, RT-PCR, and Northern blot, with much weaker expression in thymus and brain. In situ hybridization detects expression in oocytes of embryonic ovary, but not of adult ovary. RT-PCR and in situ hybridization analyses of a time course of juvenile testis development indicate that Spo11 expression begins in early meiotic Prophase I, prior to the pachytene stage, with increasing accumulation of mRNA through the pachytene stage. Taken together, these results strongly suggest that this gene encodes the functional homolog of yeast Spo11p, which in turn suggests that the mechanism of meiotic recombination initiation is conserved between yeast and mammals.

Amino Acid Sequence↗
PubMed1999

TNF-alpha suppresses IFN-gamma-induced MHC class II expression in HT1080 cells by destabilizing class II trans-activator mRNA.

Precise regulation of MHC class II gene expression is crucial for development and function of the immune system. Class II trans-activator (CIITA) has been shown to be required for constitutive and IFN-gamma-induced MHC class II transcription. TNF-alpha is commonly coexpressed with IFN-gamma during immune-mediated inflammatory responses and modulates IFN-gamma-stimulated MHC class II expression. The effect of TNF-alpha on MHC class II expression depends on cell type and cellular differentiation state. We show here that TNF-alpha suppresses IFN-gamma-induced CIITA mRNA accumulation, resulting in decreased MHC class II expression in human fibrosarcoma HT1080 cells. TNF-alpha also inhibits CIITA mRNA accumulation and protein expression in a tetracycline-regulated system without affecting promoter activity. CIITA mRNA, regulated by either IFN-gamma or tetracycline, was destabilized in the presence of TNF-alpha, suggesting that TNF-alpha utilizes a distinct mechanism to suppress MHC class II expression in HT1080 cells. Consistent with this interpretation, TNF-alpha blocked IFN-gamma-induced CIITA and MHC class II expression in mutant cells that are unresponsive to TGF-beta or IFN-beta. This is the first instance in which MHC class II expression is inhibited by destabilizing CIITA mRNA.

Fibrosarcoma↗
PubMed1999

Three-dimensional visualization of tegument/capsid interactions in the intact human cytomegalovirus.

The three-dimensional structure of the intact human cytomegalovirus (HCMV) was determined to 18-A resolution by electron cryomicroscopy and computer reconstruction. Its capsid shell is composed of pentons, hexons, and triplexes arranged on a T = 16 icosahedral lattice and is identical to that of the B-capsid isolated from host cell nuclei. An icosahedrally ordered tegument layer formed by 960 copies of filamentous density is also visualized, which interacts with the pentons, hexons, and triplexes of the underlying capsid. The observed structural similarities and differences of HCMV with those of herpes simplex virus offer insights into the significance of the different tegument components for their infection processes while maintaining similar capsids.

Capsid↗
PubMed1999

Biochemical and molecular characterization of the [NiFe] hydrogenase from the hyperthermophilic archaeon, Thermococcus litoralis.

Thermococcus litoralis is a hyperthermophilic archaeon that grows at temperatures up to 98 degrees C by fermentative metabolism and reduces elemental sulfur (S0) to H2S. A [NiFe] hydrogenase, responsible for H2S or H2 production, has been purified and characterized. The enzyme is composed of four subunits with molecular mass 46, 42, 34 and 32 kDa. Elemental analyses gave approximate values of 22 Fe, 22 S and 1 Ni per hydrogenase. EPR spectra at 70 and 5 K indicated the presence of four or five [4Fe-4S] and one [2Fe-2S] type clusters. The optimal temperature for both H2 evolution and oxidation, using artificial electron carriers, was around 80 degrees C. The operon encoding the T. litoralis enzyme is composed of four genes forming one transcriptional unit, and transcription is not regulated by S0. An unusual transcription-initiation site is located 139 bp upstream from the translational start point. Sequence analyses indicated the presence of new putative nucleotide-binding domains. Upstream from the hydrogenase operon, ORFs probably encoding a molybdopterin oxidoreductase enzyme have been identified. Based on sequence, biochemical and biophysical analyses, a model of the enzyme and the pathway of electron flow during catalysis is proposed.

Amino Acid Sequence↗
PubMed1999

An agonist anti-human CD40 monoclonal antibody that induces dendritic cell formation and maturation and inhibits proliferation of a myeloma cell line.

CD40, a 48-50 KD cell membrane molecule, member of the nerve growth factor receptor and tumor necrosis factor receptor superfamily, is an important costimulatory molecule during the immune response. Anti-CD40 monoclonal antibody (MAb) has been shown earlier to costimulate with IgM or phorbol esters resting B cells to proliferate, differentiate, secrete immunoglobulins, and switch isotype. Here we report on an agonistic mouse anti-human CD40 MAb 5C11. The specificity of this MAb was verified by flow cytometry, Western blotting, and competition with anti-CD40 MAb 89. We studied the effects of MAb 5C11 on a multimyeloma cell line, XG2, that expresses the CD40 antigen strongly and found that this MAb caused the homotypic aggregation of XG2, strongly suppressed XG2 proliferation, and led to its apoptosis after 24 hr of treatment. Interestingly, MAb 5C11 also triggered the generation, proliferation, and maturation of dendritic cells from peripheral blood monocytes, either by itself or in combination with GM-CSF and IL-4.

Animals↗