Biomedical subjects

C Zhao

Publications and source records attributed to C Zhao.

At least 163 records · Page 9Linked to original sources

PubMed1997

The human beta-defensin-1 and alpha-defensins are encoded by adjacent genes: two peptide families with differing disulfide topology share a common ancestry.

We cloned a novel human beta-defensin gene and determined its full-length cDNA sequence. The entire gene spanned more than 7 kb and included a large 6962-bp intron. The 362-bp cDNA encoded a prepropeptide that corresponded precisely to the recently identified human beta-defensin HBD-1, an antimicrobial peptide implicated in the resistance of epithelial surfaces to microbial colonization. By two-color fluorescence in situ hybridization on both metaphase chromosome and released chromatin fiber, HBD-1 gene (DEFB1 in HUGO/GDB nomenclature) mapped to chromosomal region 8p23.1-p23.2 in close proximity (within 100-150 kb) to the gene for the human neutrophil alpha-defensin HNP-1 (DEFA1). Thus, despite a complete lack of DNA sequence similarity and despite differences in their disulfide-pairing pattern, the alpha- and beta-families appear to have evolved from a common premammalian defensin gene.

Algorithms↗

PubMed1997

cDNA cloning of three cecropin-like antimicrobial peptides (Styelins) from the tunicate, Styela clava.

We cloned precursors of three new antimicrobial peptides, Styelins C, D and E, from a pharyngeal cDNA library of a tunicate, Styela clava. Preprostyelins resembled dipteran preprocecropins, while the mature domain of Styelin C resembled Cecropin P1, an antimicrobial peptide purified from the porcine intestine. Beginning with the last 6 residues of their signal sequences, Styelin C and Cecropin 1 from Drosophila virilis had 8/11 identical amino acids (72.7%). Moreover, 4 of the last 6 residues of their mature peptide domains were also identical. Styelins were shorter, by 8 residues, than dipteran cecropins and preprostyelins contained a conserved, polyanionic C-terminal extension that was absent in preprocecropins. Delineation of cecropin-like antimicrobial peptides in a protochordate supports the antiquity of this family as effectors of innate immunity in animals and it increases the likelihood that additional cecropin-like peptides will be found among other evolutionary descendants of protochordates--vertebrates.

Amino Acid Sequence↗

PubMed1997

cDNA cloning of Clavanins: antimicrobial peptides of tunicate hemocytes.

Clavanins are a family of alpha-helical antimicrobial peptides found in hemocytes of the tunicate, Styela clava. We examined a cDNA library prepared from pharyngeal tissues of S. clava and sequenced 24 clones that encoded prepropeptides of Clavanins A, C, D or E. These sequences indicated that Clavanins are synthesized as 9.2 kDa prepropeptides which contain a 19-residue signal peptide, followed in turn by a highly polar 'pro' region (LEERKSEEEK) with five glutamic acid residues, the 23 residues of the mature Clavanin peptide, the glycine residue needed for its amidation and a 27-residue polar C-terminal extension that is removed in later processing. Although the signal sequence and anionic propiece of Clavanin precursors share features with corresponding regions in precursors of the certain frog peptides, including ranalexin, gaegurins, dermaseptins and deltorphins, their unique multipartite structure suggests that they are not actually homologues of these amphibian peptides.

Amino Acid Sequence↗

PubMed1997

Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues.

Leptin's effects are mediated by interactions with a receptor that is alternatively spliced, resulting in at least five different murine forms: Ob-Ra, Ob-Rb, Ob-Rc, Ob-Rd, and Ob-Re. A mutation in one splice form, Ob-Rb, results in obesity in mice. Northern blots, RNase protection assays, and PCR indicate that Ob-Rb is expressed at a relatively high level in hypothalamus and low level in several other tissues. Ob-Ra is expressed ubiquitously, whereas Ob-Rc, -Rd, and -Re RNAs are only detectable using PCR. In hypothalamus, Ob-Rb is present in the arcuate, ventromedial, dorsomedial, and lateral hypothalamic nuclei but is not detectable in other brain regions. These nuclei are known to regulate food intake and body weight. The level of Ob-Rb in hypothalamus is reduced in mice rendered obese by gold thioglucose (GTG), which causes hypothalamic lesions. The obesity in GTG-treated mice is likely to be caused by ablation of Ob-Rb-expressing neurons, which results in leptin resistance.

Alternative Splicing↗

PubMed1997

Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor.

ATP-sensitive potassium channels (K-ATP channels) couple cell metabolism to electrical activity and are important in the physiology and pathophysiology of many tissues. In pancreatic beta-cells, K-ATP channels link changes in blood glucose concentration to insulin secretion. They are also the target for clinically important drugs such as sulphonylureas, which stimulate secretion, and the K+ channel opener diazoxide, which inhibits insulin release. Metabolic regulation of K-ATP channels is mediated by changes in intracellular ATP and Mg-ADP levels, which inhibit and activate the channel, respectively. The beta-cell K-ATP channel is a complex of two proteins: an inward-rectifier K+ channel subunit, Kir6.2, and the sulphonylurea receptor, SUR1. We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP.

ATP-Binding Cassette Transporters↗

PubMed1997

Fe- and Co-bleomycins bound to site specific and nonspecific DNA decamers: comparative binding and reactivity of their metal centers.

Co- and Fe-bleomycins (Blms) have been reacted with DNAa, d(GGAAGCTTCC)2, containing a specific site for cleavage, and DNAb, d(GGAAATTTCC)2, a closely related nonspecific 10-mer, to survey whether features of structure and reactivity of these adducts vary systematically as a function of the base sequence of the DNA oligomer. The ESR spectrum of NO-Fe(II)BlmDNAa is rhombically perturbed in comparison with that of NO-Fe(II)BlmDNAb, which is nearly identical to the spectrum of NO-Fe(II)Blm. The ESR spectrum of Fe(III)BlmDNAa in phosphate buffer is low-spin; that of Fe(III)BlmDNAb is high-spin as seen with Fe(III)Blm alone. According to absorbance spectroscopy, O2-Fe(II)BlmDNAa is stabilized in comparison with the DNAb adduct. Similar stabilization of O2-Co(II)Blm bound to DNAa but not to DNAb was also observed by ESR spectroscopy. HO2(-)-Co(III)Blm A2 binds in slow exchange on the NMR time scale to DNAa at its 5'-G-pyrimidine-3' site of cleavage. In contrast, fluorescence and NMR spectroscopy demonstrate that most of HO2(-)-Co(III)Blm A2 binds stoichiometrically in fast exchange to DNAb. The reactions of Fe(III)BlmDNAa and Fe(III)BlmDNAb with ascorbate and O2 reveal that the latter becomes activated and cleaves its 10-mer, producing base propenals, at a faster initial rate. Thus, in two series of metallobleomycins, (A) NO-Fe(II)Blm, O2-Fe(II)Blm, Fe(III)Blm in phosphate buffer, and HO2(-)-Fe(III)Blm and (B) O2-Co(II)Blm and HO2(-)-Co(III)Blm, the metal domain of each species interacts differently with DNA depending upon its base sequence.

Antibiotics, Antineoplastic↗

PubMed1997

Serine palmitoyltransferase (scs1/lcb2) mutants have elevated copy number of the L-A dsRNA virus.

The microsomal fraction isolated form serine palmitoyltransferase (lcb2/scs1) mutants is enriched in a 90 kDa protein. The protein was identified as the major coat (Gag) protein of the L-A dsRNA virus particles by partial sequencing and by its interaction with anti-Gag antibodies. The total amount of Gag in whole-cell lysates of scs1/lcb2 mutant cells is greater than in wild-type lysates indicating that the enrichment of the protein in the microsomal fraction of scs1/lcb2 mutant cells may result from increased copy number of the L-A dsRNA virus. This is supported by the findings that the mutants also have increased levels of L-A dsRNA. Altered sphingolipid synthesis in the scs1 mutant cells appears to increase the copy number of the L-A viral particles.

Acyltransferases↗

PubMed1997

Clavanins, alpha-helical antimicrobial peptides from tunicate hemocytes.

Hemocytes from the invertebrate Styela clava, a solitary tunicate, contained a family of four alpha-helical antimicrobial peptides that were purified, sequenced and named clavanins A, B, C and D. Each clavanin contained 23 amino acid residues and was C-terminally amidated. The tunicate peptides resembled magainins in size, primary sequence and antibacterial activity. Synthetic clavanin A was prepared and displayed comparable antimicrobial activity to magainins and cecropins. The presence of alpha-helical antimicrobial peptides in the hemocytes of a urochordate suggests that such peptides are primeval effectors of innate immunity in the vertebrate lineage.

Amino Acid Sequence↗

PubMed1997

Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from Dioncophyllaceae and Ancistrocladaceae species.

Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from Dioncophyllaceae and Ancistrocladaceae species. International Journal for Parasitology 27: 29-32. Naphthylisoquinoline alkaloid-containing extracts (10 micrograms ml-1) of species belonging to the Dioncophyllaceae and the Ancistrocladaceae, 2 small tropical plant families, display pronounced in vitro activities against exoerythrocytic stages of Plasmodium berghei (Anka), developing in human hepatoma cells (Hep G2). The highest activities were obtained with CH2Cl2 root and bark extracts, and a CH2Cl2/NH3 leaf extract from Triphyophyllum peltatum, a CH2Cl2/NH3 root extract from Ancistrocladus abbreviatus, and a CH2Cl2 leaf extract from A. tectorius. The degrees of growth inhibition ranged within 27.7-70.0%. The commercially available drug primaquine diphosphate (25 micrograms ml-1) caused a comparable effect (62.1%) in the same test system.

Animals↗

PubMed1997

Response of substance P-immunoreactive nerve fibres in the anterior pituitary to plasma oestrogen levels in the rat.

The mammalian anterior pituitary has recently been shown to be innervated by substantial amounts of peptidergic nerve fibres. It has also been found that adrenalectomy increases the amount of calcitonin gene-related peptide-like immunoreactive nerve fibres in the anterior pituitary of the rat, and that stimulation of the nerve fibres in vitro can enhance release of ACTH. In the present study, the density of substance P-like immunoreactive nerve fibres in the anterior pituitary of the rat were examined in relation to variations in plasma oestrogen status. The amount of substance P-like immunoreactive nerve fibres increased significantly (P < 0.001) after ovariectomy, and decreased significantly (P < 0.01) under oestrogen replacement, in a dose-dependent manner. The results suggest the possibility of the direct neural involvement of oestrogen secretion in anterior pituitary regulation, which further substantiates the hypothesis of neural-humoral dual regulation of the mammalian anterior pituitary.

Animals↗

PubMed1997

Acetaminophen cytotoxicity in mouse eye: mitochondria in anterior tissues are the primary target.

Acetaminophen (APAP) injected into C57BL/6 mice (cytochrome P450 inducer-responsive strain) that had been pretreated with b-naphthoflavone (BNF) produced ocular tissue damage, including cataract. Our previous histocytochemical studies showed that tissue damage spread in association with the flow of the aqueous humor and appeared first in the ciliary epithelium, followed by the iris and corneal endothelium and, finally, the lens. The neural retina, retinal pigmented epithelium and choroid remained unaffected. A close examination of the affected tissues indicated that mitochondria are the primary target of APAP cytotoxicity. In order to investigate whether the respiratory capacity of mitochondria is more sensitive to APAP cytotoxicity than mitochondrial morphology, we determined in this work the oxygen uptake by eye tissues dissected from BNF-pretreated and APAP-injected C57BL/6 mice. Oxygen uptake by the ciliary body/iris decreased about 60% at 90 min and 85% at 120 min after APAP administration. The oxygen uptake was inhibited about 50% by 10 microM rotenone. Since the earliest sign of mitochondrial damage was noted at 120 min, the result indicates that mitochondrial energy dysfunction precedes morphological alterations. It was also observed that oxygen uptake by the retina remained unaffected at least for 120 min after APAP administration; therefore, it is evident that the retina and, possibly, other posterior tissues as well are resistant to APAP cytotoxicity, not only in their morphology but, also, in their capacity of mitochondrial energy metabolism.

Acetaminophen↗

PubMed1997

DNA adducts in human nasal mucosa and white blood cells from smokers and non-smokers.

The goal of the present study was to measure the levels of DNA adducts in human nasal mucosa cells and in total white blood cells in relation to smoking. DNA was isolated from samples of 20 healthy volunteers (six smokers and 14 non-smokers). The levels of DNA adducts were measured by 32P-postlabelling assay. In smokers the mean DNA adduct levels were 3.3 and 17.0 adducts/10(8) nucleotides in total white blood cells and nasal mucosa cells respectively. The corresponding values in non-smokers were 2.0 and 6.8 adducts/10(8) nucleotides. The mean adduct level was significantly higher in nasal mucosa cells than in total white blood cells both in smokers and non-smokers. The mean adduct levels in smokers' nasal mucosa cells were significantly higher than those in non-smokers. Thus the nasal mucosa cells constituted a sensitive tissue for the determination of cigarette smoking induced DNA adducts. Combining the sensitivity of the 32P-postlabelling assay with the specificity of the nasal mucosa to the airborne chemical exposures, the DNA adduct analysis from human nasal mucosa cells represents a method of choice in the assessment of exposure to airborne carcinogens.

Adult↗

PubMed1997

Porcine polymorphonuclear leukocytes generate extracellular microbicidal activity by elastase-mediated activation of secreted proprotegrins.

Antimicrobial peptides of several structural classes have been found in phagocytes and epithelial cells of many animals. The broadly microbicidal protegrins (PG1, -2, and -3) were originally isolated as 16 to 18-amino-acid peptides from pig neutrophil lysates, but the corresponding cDNA sequences encoded much larger precursors that belonged to the cathelicidin family of antimicrobial peptides. We explored the storage, secretion, and microbicidal activation of protegrins in porcine neutrophils and in a model system consisting of recombinant proprotegrin 3 (pPG3) and various serine proteases and their inhibitors. Protegrins were stored in neutrophils as inactive proforms that were cleaved by neutrophil elastase to mature protegrins during the preparation of granule lysate and during phorbol myristate acetate-stimulated granule secretion from intact neutrophils. Recombinant pPG3 was efficiently cleaved by trace amounts of human neutrophil elastase or equivalent amounts of elastase activity from porcine neutrophils, but pPG3 was relatively resistant to porcine pancreatic elastase or human neutrophil cathepsin G. The recombinant pPG3 and neutrophil proprotegrins lacked microbicidal activity, but the mature protegrins generated in the elastase-mediated cleavage reaction were as active against Listeria monocytogenes as the chemically synthesized protegrin. The secretion and elastase-mediated activation of proprotegrins accounted for much of the stable microbicidal activity of porcine neutrophil secretions against L. monocytogenes. Secreted proprotegrins and trace amounts of elastase constitute a binary microbicidal system that is likely to contribute to the antimicrobial activity of porcine inflammatory fluids.

Amino Acid Sequence↗

PubMed1997

Integrin-mediated regulation of hematopoiesis: do BCR/ABL-induced defects in integrin function underlie the abnormal circulation and proliferation of CML progenitors?

Hematopoiesis takes place in close contact with the marrow microenvironment. Normal progenitors adhere through a variety of receptors to stroma and extracellular matrix components, including fibronectin. Adhesion through integrins to fibronectin may not only serve to anchor progenitors to the microenvironment but also to directly alter the proliferative behavior of normal hematopoietic progenitors. Chronic myelogenous leukemia (CML) is a malignant disease of the hematopoietic stem cell. At the molecular level, CML is characterized by the BCR/ABL gene rearrangement which encodes for the oncoprotein, p210bcr-abl. Presence of the p210bcr-abl tyrosine kinase is necessary and sufficient for the malignant transformation of hematopoietic cells. Clinically, CML is characterized by an abnormal, premature release of primitive progenitors and precursors in the blood and by the continuous proliferation of the malignant progenitor population. In vitro, CML progenitors fail to adhere to or be regulated by marrow stroma. Since CML progenitors express similar numbers of integrin adhesion receptors as normal progenitors, functional rather than quantitative differences of these receptors on CML progenitors may be responsible for the abnormal circulation and proliferation of the malignant clone. In this manuscript we will review the role of integrin adhesion receptors present on normal hematopoietic progenitors in the regulation of their proliferation and discuss signal transduction mechanisms that may be responsible for these effects. We will also discuss the integrin defect in CML which may be caused by the presence of the oncoprotein, P210bcr-abl, and may explain the abnormal trafficking and proliferation observed in CML.

Bone Marrow↗

PubMed1997

[A new type of intellectualized Y-maze].

This paper describes the hardware and software of an intellectualized Y-maze with a microcomputer, which controls the whole procedure of discrimination learning test for rats or mice. By monitoring the action of the animal with the infrared photoelectrical sensors, its determination is accurate and timing precise. Due to working on the platform of WINDOWS, the interface is friendly and the operation is convenient and simple.

Animals↗

PubMed1997

[A randomized controlled clinical study of cefetamet pivoxil versus cefixime in the treatment of 99 cases bacterial infections].

A randomized controlled clinical study of cefetamet pivoxil (CAT) compared with cefixime (CFX) was conducted to evaluate its safety and efficacy in treating bacterial infections. 99 patients suffering from respiratory and urinary tract infections were enrolled in the study. 10 patients were excluded within the first 72 hrs after initiation of the study. 55 and 54 were evaluated for the safety of CAT and CFX respectively. 51 patients in the CAT group and 48 patients in the CFX group were evaluated for the efficacy. The doage of CAT was 250-500 mg and CFX was 200 mg, twice daily orally for 7-10 days. The results showed that the clinical efficacy rates of CAT and CFX were 94.1% (48/51) and 91.7% (44/48), the bacterial clearance rates were 95.3% and 95.1%, respectively. Adverse drug reactions occurred in 9.1% and 7.4% in the two groups respectively. The study demonstrated that there were no satistical differences between the two groups with respect to clinical efficacy, bacterial clearance and adverse reactions.

Adolescent↗

PubMed1997

[Transmission electron microscopic study on eosinophil degranulation in nasal mucosa in allergic rhinitis].

To observe the ultrastructure of eosinophil (EOS) degranulation in nasal mucosa in allergic rhinitis, nasal mucosa biopsies from patients with perennial allergic rhinitis (PAR, n = 13) pollinosis (PS, n = 9) subjects and normal controls (n = 3) were processed and the ultrastructure changes of EOS degranulation were examined under transmission electron microscope and routine histopathological observation. The ultrastructure of EOS degranulation in nasal mucosa collected from PAR and PS patients in their remission period differed from that in their attacking period, though there was no distinct differences in the distribution patterns of EOS. Increased cell membrane projections, eminent cytoplasm vacuolization, inconsistent density of granules with its crystalloid being lost, plus tissue edema and damage of collagen fibers in adjacent areas of degranulating EOS were among the most important ultrastructural changes of EOS in attacking period. The interrelations of EOS, mast cells (MC) and T-lymphocytes play important roles in the pathogenesis of allergic rhinitis.

Adult↗

PubMed1997

[Senility-preventing effect of erlingcankang decoction].

Experiments with Erlingcankang Decoction showed that when given to silk worms it could noticeably prolong the growth period of larvae and raise an average of 10-day survival of the male moths; when given to mice it could prolong their life; and when given to on old rats it could markedly raise the contents of SOD in the liver and red cells, lower the content of MAO-B in the brain, LF in the brain and adrenal gland and also LPO in the liver.

Aging↗