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Biomedical subjects

Hong Zhu

Publications and source records attributed to Hong Zhu.

At least 91 records · Page 5Linked to original sources

[Determination of trace elements in ancient Cheshi human costa by ICP-AES].

In recent years, the study on palaeodiet is an important research in the international archaeological field. Trace elements in human bones can supply a lot of valuable information to reconstruct ancient diet. In this study, The trace elements in Bronze age Cheshi human costa from Chubeixi cemetery in shanshan, Xinjiang were determined by ICP-AES. The sample was dissolved by HNO3 and HCl. Under the optimum conditions, eight elements can be determined simultaneously. The recoveries of the method are in the range of 87.4%-106.6%, and RSDs are in the range of 0.5%-3.3%. The method is simple, rapid, precise and convenient to operate. The results would be helpful for research in archaeology. This analysis established Xinjiang' s consult system of trace elements analysis for ancient human bones. The effects of various concentrations of acid solution on analysis results, the interference of coexistent elements, standard addition recovery, and precision of the method were investigated.

Adsorption↗

In vitro and in vivo modulations of benzo[c]phenanthrene-DNA adducts by DNA mismatch repair system.

Benzo[c]phenanthrene dihydrodiol epoxide (B[c] PhDE) is well known as an important environmental chemical carcinogen that preferentially modifies DNA in adenine residues. However, the molecular mechanism by which B[c]PhDE induces tumorigenesis is not fully understood. In this report, we demonstrate that DNA mismatch repair (MMR), a genome maintenance system, plays an important role in B[c]PhDE-induced carcinogensis by promoting apoptosis in cells treated with B[c]PhDE. We show that purified human MMR recognition proteins, MutS(alpha) and MutSbeta, specifically recognized B[c]PhDE-DNA adducts. Cell lines proficient in MMR exhibited several-fold more sensitivity to killing than cell lines defective in either MutS(alpha) or MutL(alpha) by B[c]PhDE; the nature of this sensitivity was shown to be due to increased apoptosis. Additionally, wild-type mice exposed to B[c]PhDE had intestinal crypt cells that underwent apoptosis significantly more often than intestinal crypt cells found in B[c]PhDE-treated Msh2(-/-) or Mlh1(-/-) mice. These findings, combined with previous studies, suggest that the MMR system may serve as a general sensor for chemical-caused DNA damage to prevent damaged cells from mutagenesis and carcinogenesis by promoting apoptosis.

Adaptor Proteins, Signal Transducing↗

Visualization of proliferating cells in the adult mammalian brain with the aid of ribonucleotide reductase.

Proliferating cells are hardly detectable in the adult mammalian brain by microscopy of stained sections, but after pre-labeling with radioactive thymidine or 5'-bromo-2-deoxyuridine (BrdU), either marks the nucleus, as do mitosis-related proteins such as Ki67 and PCNA. Engineered virus may also be used to mark proliferating cells. One alternative approach is to use the enzyme ribonucleotide reductase (RNR), expressed by proliferating cells, but not by quiescent ones. A monoclonal antibody against the M1 subunit of RNR was used to visualize proliferating cells in the brains of adult normal rats, rabbits, pigs and sheep. Stem cells were distinctly outlined. In the subgranular layer in the hippocampal dentate gyrus, most RNR immunoreactive cells were bipolar to multipolar, and had a large cell body and long processes. Two different populations of RNR expressing cells were visualized in the subventricular zone in the forebrain, one dominated by small, bipolar cells extending into the rostral migratory stream, while the other was formed by large multipolar cells, adjacent to the ependyma, with processes extending to the lateral ventricle. Furthermore, rare RNR-expressing cells were recognized throughout the brain. The RNR immunoreactive cells were immature, as they did not express any marker characterizing differentiated neurons and glial cells, except for a fraction that co-expressed the gliofibrillary acidic protein. BrdU and RNR were co-localized in proliferating cells in animals pretreated with BrdU. We conclude that RNR immunohistochemistry can accurately visualize proliferating cells, including stem cells, in adult mammalian brains. The occurrence of processes at cell proliferation is elucidated. Further, the advocated approach does not require any pre-labeling, and can be carried out on fixed tissues.

Animals↗

The PHD finger of the chromatin-associated protein ING2 functions as a nuclear phosphoinositide receptor.

Phosphoinositides (PtdInsPs) play critical roles in cytoplasmic signal transduction pathways. However, their functions in the nucleus are unclear, as specific nuclear receptors for PtdInsPs have not been identified. Here, we show that ING2, a candidate tumor suppressor protein, is a nuclear PtdInsP receptor. ING2 contains a plant homeodomain (PHD) finger, a motif common to many chromatin-regulatory proteins. We find that the PHD fingers of ING2 and other diverse nuclear proteins bind in vitro to PtdInsPs, including the rare PtdInsP species, phosphatidylinositol 5-phosphate (PtdIns(5)P). Further, we demonstrate that the ING2 PHD finger interacts with PtdIns(5)P in vivo and provide evidence that this interaction regulates the ability of ING2 to activate p53 and p53-dependent apoptotic pathways. Together, our data identify the PHD finger as a phosphoinositide binding module and a nuclear PtdInsP receptor, and suggest that PHD-phosphoinositide interactions directly regulate nuclear responses to DNA damage.

1-Phosphatidylinositol 4-Kinase↗

Phylogenetic analysis of rubella virus isolated during a period of epidemic transmission in Italy, 1991-1997.

To study the molecular epidemiology of rubella virus during endemic transmission, phylogenetic analysis of the nucleotide sequence of the E1 gene was done with 31 isolates collected in northern Italy during 1991-1997, a period spanning 3 epidemics. The viruses segregated into distinct genotypic strains. Cocirculation of genotypic strains was detected; however, each epidemic was associated with specific strains, and strain displacement occurred concomitantly with each epidemic. Although most of the viruses from Italy belonged to rubella genotype I and many were related to viruses isolated concurrently in other European countries, 3 viruses belonged to rubella genotype II, which previously had been isolated only in Asia. Thus, intercontinental importation of viruses also occurred.

Adult↗

Morphine-induced potentiation in the dentate gyrus of the hippocampus involves norepinephrine.

We examined the role of norepinephrine in the morphine-induced potentiation in the dentate gyrus of the hippocampus in chronically implanted freely moving rats. The population spikes of the field potentials in the dentate gyrus following perforant path stimulation were recorded before and after morphine injection. We found that a single dose of morphine sulfate (5 mg/kg, i.v.) resulted in a long-lasting augmentation in the amplitudes of population spikes. When pretreated with propranolol (5 mg/kg, i.v.), a beta-adrenoceptor antagonist, the morphine-induced potentiation was significantly attenuated. These results suggested that an increase in norepinephrine release in the hippocampus contributed to the morphine-induced potentiation.

Adrenergic beta-Antagonists↗

Low density lipoprotein receptor-related protein-mediated membrane translocation of 12/15-lipoxygenase is required for oxidation of low density lipoprotein by macrophages.

Oxidation of low density lipoprotein (LDL) is the key step for the development of atherosclerosis. The 12/15-lipoxygenase expressed in macrophages is capable of oxygenating linoleic acid esterified to cholesterol in the LDL particle, and thus this enzyme is presumed to initiate LDL oxidation. We recently reported that LDL receptor-related protein (LRP) was required for the enzyme-mediated LDL oxidation by macrophages and suggested the selective uptake of cholesterol ester from LDL to the plasma membrane (Xu, W., Takahashi, Y., Sakashita, T., Iwasaki, T., Hattori, H., and Yoshimoto. T. (2001) J. Biol. Chem. 276, 36454-36459). To elucidate precise mechanisms of lipoxygenase-mediated LDL oxidation, we investigated the intracellular localization of 12/15-lipoxygenase. The 12/15-lipoxygenase was predominantly detected in cytosol of resting peritoneal macrophages and of macrophage-like J774A.1 cells permanently transfected with the cDNA for the enzyme. When the cells were treated with LDL and subjected to subcellular fractionation, the 12/15-lipoxygenase was detected in the membranes with a concomitant decrease in cytosol as shown by Western blot analysis. The levels of the enzyme associated with the membrane reached maximum in 15 min after LDL addition and then decreased. However, the enzymatic activity of 12/15-lipoxygenase in the membrane fraction was very weak even after LDL treatment. This fact supports the suicide inactivation of the enzyme by the oxygenation of cholesterol ester transferred from the LDL particle to the plasma membrane. Immunohistochemical analysis using an antibody against 12/15-lipoxygenase revealed that the plasma membrane was the major site of the enzyme translocation by the LDL treatment. LDL-dependent 12/15-lipoxygenase translocation was inhibited by a blocking antibody against LRP. Furthermore, an enzyme translocation inhibitor, L655238, inhibited the LDL oxidation caused by the 12/15-lipoxygenase. We propose that cholesterol ester selectively transferred from the LDL particle to the plasma membrane via LRP is oxygenated by 12/15-lipoxygenase translocated to this membrane.

Animals↗

RAGE mediates amyloid-beta peptide transport across the blood-brain barrier and accumulation in brain.

Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta interaction with receptor for advanced glycation end products (RAGE)-bearing cells in the vessel wall results in transport of Abeta across the blood-brain barrier (BBB) and expression of proinflammatory cytokines and endothelin-1 (ET-1), the latter mediating Abeta-induced vasoconstriction. Inhibition of RAGE-ligand interaction suppresses accumulation of Abeta in brain parenchyma in a mouse transgenic model. These findings suggest that vascular RAGE is a target for inhibiting pathogenic consequences of Abeta-vascular interactions, including development of cerebral amyloidosis.

Aged↗

Redistribution of neurofilaments and accumulation of beta-amyloid protein after brain injury by rotational acceleration of the head.

Rotational acceleration of the head, as occurs in falls, car crashes, and sport injuries, may result in diffuse brain damage, with acute and chronic neurological and psychiatric symptoms. The present study addresses the effects of rotational trauma on the neuronal cytoskeleton, which stabilizes perikaryal, dendritic and axonal shape and function. The study focuses upon the distribution of (1) the phosphorylated form of the heavy neurofilament subunit, (2) the light neurofilament subunit, and (3) beta-amyloid, a marker for brain injury. While normally restricted to axons, the phosphorylated heavy neurofilament subunits were drastically decreased in the axons after rotational trauma. Instead, they accumulated in the neuronal perikarya, normally devoid of the phosphorylated subunit. This alteration was seen, not only in the cerebral cortex, but also in the hippocampus, the cervical spinal cord, the cerebellum, the cranial nerves and the pyramidal tract. The distribution of the light subunit of neurofilaments was also altered post trauma. Only a weak beta-amyloid immunoreactivity was detected in the brains of control animals. Promptly after the trauma, a large number of beta-amyloid positive neurons appeared. Intensely co-localized immunoreactivity for the light subunit of neurofilaments and of beta-amyloid was seen 3 days after the rotational trauma axons of in the subcortical white matter and in the granule cell layer of the dentate gyrus as well as in neurons of the hypoglossal nucleus. The reported alterations in the central nervous system neurons are similar to those in the human brain after closed head injury and in chronic degenerative diseases. Regions of importance for social behavior, memory and body movement were affected.

Acceleration↗

Bacteria associated with cysts of the soybean cyst nematode (Heterodera glycines).

The soybean cyst nematode (SCN), Heterodera glycines, causes economically significant damage to soybeans (Glycine max) in many parts of the world. The cysts of this nematode can remain quiescent in soils for many years as a reservoir of infection for future crops. To investigate bacterial communities associated with SCN cysts, cysts were obtained from eight SCN-infested farms in southern Ontario, Canada, and analyzed by culture-dependent and -independent means. Confocal laser scanning microscopy observations of cyst contents revealed a microbial flora located on the cyst exterior, within a polymer plug region and within the cyst. Microscopic counts using 5-(4,6-dichlorotriazine-2-yl)aminofluorescein staining and in situ hybridization (EUB 338) indicated that the cysts contained (2.6 +/- 0.5) x 10(5) bacteria (mean +/- standard deviation) with various cellular morphologies. Filamentous fungi were also observed. Live-dead staining indicated that the majority of cyst bacteria were viable. The probe Nile red also bound to the interior polymer, indicating that it is lipid rich in nature. Bacterial community profiles determined by denaturing gradient gel electrophoresis analysis were simple in composition. Bands shared by all eight samples included the actinobacterium genera Actinomadura and STREPTOMYCES: A collection of 290 bacteria were obtained by plating macerated surface-sterilized cysts onto nutrient broth yeast extract agar or on actinomycete medium. These were clustered into groups of siblings by repetitive extragenic palindromic PCR fingerprinting, and representative isolates were tentatively identified on the basis of 16S rRNA gene sequence. Thirty phylotypes were detected, with the collection dominated by Lysobacter and Variovorax spp. This study has revealed the cysts of this important plant pathogen to be rich in a variety of bacteria, some of which could presumably play a role in the ecology of SCN or have potential as biocontrol agents.

Animals↗

[Albumin kinetics in patients with severe sepsis].

OBJECTIVE: To explore the mechanism of hypoalbuminemia in patients with severe sepsis. METHODS: I(125)-labeled albumin was administered intravenously to 10 health volunteers and 10 patients with severe sepsis. Blood samples were taken at 0, 1, 2, 4, 8, 12, 24 hours and 2, 3, 4, 5, 6, 7, 9, 11, 13, 15, 18, 22, 25 days for the measurement of the dose of gamma-radiation and the curve of concentration and time. Then the half-life time (t(1/2)), apparent volume of distribution (V(d)) and transportation rate (K(12)) from center compartment to side compartment of albumin were calculated. RESULTS: The half-life time in septic group was obviously shorter than that in control group (8.2 +/- 1.4 vs. 12.5 +/- 1.7, P < 0.01). The transportation rate in the septic group was higher than that in the control group [(4.4 +/- 1.9) x 10(-2)/h vs. (2.4 +/- 0.6) x 10(-2)/h, P < 0.05]. There was no significant difference in apparent volume of distribution between the two groups. CONCLUSIONS: In patients with severe sepsis, the distribution rate of albumin from vessel to tissue was obviously increased and the decomposition rate of albumin was markedly improved.

Adult↗

[Mitochondrial DNA sequence variations of Keriyan in the Taklamakan desert].

The Keriyans live in the center of the Taklamakan desert of Xinjiang Province and they have never married with outsiders. Nobody knows clearly how they immigrated here and who was their origin. The mtDNA hypervariable segment I sequences were sequenced in 75 Keriyans. Seventy-one unique HVS I types were identified, varying at 68 nucleotide positions. Nucleotide diversity and the mean pairwise differences of Keriyan are intermediate between those reported for Eastern and Western populations. Keriyan's low Tajima's D statistics and bell-shaped pairwise-difference distributions can be interpreted as the hallmark of an ancient population expansion. Phylogenetic analysis shows Central Asian populations occupy a position intermediate between the Eastern and Western populations, moreover, the Keriyan presents shorter genetic distances to Xinjiang Uighur and Uighur in other places than to other populations.

Base Sequence↗

[Experience of perioperative nursing of benign prostate hyperplasia patients with diabetes].

OBJECTIVE: To study the perioperative nursing the benign prostate hyperplasia (BPH) patients with diabetes mellitus. METHODS: The nursing and treatment of 126 BPH patients with diabetes mellitus were investigated. RESULTS: Satisfactory nursing effect was seen in 122 of the patients, and postoperative improvement was significantly associated with post-void residual urine volume and urine flow in the 122 patients. CONCLUSIONS: Perioperative nursing lays an important base for successful operation and ensures curative effect of BPH patients with diabetes mellitus.

Aged↗

[Effect of Citrus aurantium extract on L-type calcium currents in ventricular myocytes of single guinea pigs].

OBJECTIVE: To determine the effect of citrus aurantium extract (CAE) on L-type calcium currents (ICa-L) in ventricular myocytes of guinea pigs. METHODS: Single myocytes were dissociated by enzymatic dissociation method. The whole-cell patch-clamp recording technique was used to record the change of calcium current after the administration of CAE. RESULTS: 1. CAE 4 x 10(-3), 2 x 10(-2), 4 x 10(-2), and 1 x 10(-1) g/ml increased the ICa-L by 15.89%, 29.01%, 52.03% and 59.76% (P < 0.05), respectively. 2. CAE 2 x 10(-1) and 4 x 10(-1) g/ml decreased the ICa-L by 16.61% and 30.87% (P < 0.05), respectively. CAE changed the ICa-L significantly, but did not change the shape of I-V curves. CONCLUSIONS: CAE 4 x 10(-3)-1 x 10(-1) g/ml can increase the L-type calcium current in guinea pig ventricular myocytes significantly in a concentration-dependent manner, and promote the opening of calcium channel. CAE 2 x 10(-1)-4 x 10(-1) g/ml may inhibit the L-type calcium channels of ventricular myocytes, and depress the opening of calcium channel.

Animals↗

[Therapeutic effect of the recombinant human granulocyto colony-stiimulating factor on radiation-induced agranulocytosis models of mice].

OBJECTIVE: To observe the effect of the recombinant human granulocyto colony-stimulating factor (rhG-CSF) on radiation-induced neutropenia models of mice. METHODS: rhG-CSF in 2 different doses (10 micrograms.kg-1.d-1 and 30 micrograms.kg-1.d-1) was injected respectively to radiation-induced neutropenia models of mice. The effect of rhG-CSF on the weight of the spleen, CFU-S, leukocyte counts, neutrophil counts, and CFU-GM of the marrow cell culture was observed. RESULTS: Both 30 and 10 micrograms.kg-1.d-1 of rhG-CSF increased CFU-GM of the marrow cell culture and the peripheral leukocyte and neutrophil, showing a significant difference compared with the NS control group (P < 0.05). CONCLUSION: rhG-CSF has a significant therapeutic effect on radiation-induced agranulocytosis models of mice.

Agranulocytosis↗

Discovery of aminothiazole inhibitors of cyclin-dependent kinase 2: synthesis, X-ray crystallographic analysis, and biological activities.

High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC(50) values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.

Animals↗

Utilization of commercial non-chitinase enzymes from fungi for preparation of 2-acetamido-2-deoxy-D-glucose from beta-chitin.

Commercial non-chitinase enzymes from Aspergilus niger, Acremonium cellulolyticus and Trichoderma viride were investigated for potential utilization in the preparation of 2-acetamido-2-deoxy-D-glucose (N-acetyl-D-glucosamine, GlcNAc) from chitin. Among the tested enzymes, cellulase A. cellulolyticus exhibited highest chitinolytic activity per weight toward amorphous chitin and beta-chitin from squid pen. The optimum pH of the enzyme was 3 where it produced two major hydrolytic products, GlcNAc and N,N'-diacetylchitobiose ([GlcNAc](2)). The product ratio, GlcNAc:[GlcNAc](2), increased while the total yield decreased as the pH was raised from 3. All of the [GlcNAc](2) produced at pH 3 can be converted in situ to GlcNAc by mixing cellulase A. cellulolyticus with one of several other enzymes from A. niger resulting in a higher yield of GlcNAc. An appropriate mixing ratio of cellulase A. cellulolyticus to another enzyme was 9:1 (w/w) and an optimum substrate concentration was 20 mg/mL.

Acetylglucosamine↗