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Biomedical subjects

J Zhao

Publications and source records attributed to J Zhao.

At least 757 records · Page 42Linked to original sources

[Cisplatin or combined cisplatin and 60Co radiation in the treatment of advanced lung cancer--report of 145 cases].

The result of 145 patients with advanced primary lung cancer treated by cisplatin alone or combined cisplatin and 60Co radiation from June 1981 to August 1983 is reported. 75 of these cases were clinical stage III and 70 stage IV. 57 (39%) were proved by pathology and 64 (44%) by cytology, totalling 121 (83%) as non-small cell lung cancers. The other 24 (17%) were diagnosed by clinical means. All the patients were divided into two groups. Group I, 26 cases were treated by cisplatin alone. In this group, no complete response was found, the partial response rate was 31% and 1-year survival rate was 40%. Group II, 119 patients were treated by the combination of cisplatin and 60Co radiation. Complete response rate was 16%, partial 59%, 1 and 2-year survival rates were 52% and 33%, respectively. The results show that the combination of cisplatin and 60Co therapy is more effective for the advanced lung cancers.

Adenocarcinoma↗

The tunnelling conductance of molecularly ordered metalloprotein arrays.

Metalloproteins can be self-assembled in molecularly ordered, electrochemically addressable arrays. We report here on a study of the transport characteristics of the blue copper protein, azurin, from Pseudomonas aeruginosa, by a combination of electrochemical and scanning probe techniques (scanning tunnelling microscopy and conducting atomic force microscopy). Redox-switchable chemisorbed molecular arrays can be formed from both wild-type and mutant proteins using the strong affinity of cysteine residue thiolates for pristine gold surfaces. The molecular transconductance of single protein molecules within these arrays has been studied under controllable conditions where it has been additionally possible to resolve the effects of protein mechanical perturbation. Although tunnelling appears to be non-resonant and adequately explained through the use of a square barrier model, under some conditions the contribution of the redox-active copper centre to conductance is resolvable.

Azurin↗

Multivalent ligand system carrying enkephalin and neurotensin coimmobilized on liposomes.

A multivalent ligand system was constructed by coimmobilization of two kinds of peptide ligands, enkephalin and neurotensin derivatives having a dioctadecyl group, on dimyristoylphosphatidylcholine (DMPC) liposomes. The enkephalin derivatives are Tyr-D-Ala-Gly-Trp-Leu-(Sar-Sar-Pro)n-[N(C18H37)2] (Enk3nD, n = 0, 1, 2), where a dioctadecyl group was connected to the C-terminal side of enkephalin directly or through a hydrophilic and flexible spacer chain of different lengths. The neurotensin derivatives are Ac-Glu[N(C18H37)2l-(Sar-Sar-Pro)n-Arg-Arg-Pro-Tyr-Ile-Leu-OH (D3nNT, n = 0, 1, 2, 3). The derivatives were spontaneously immobilized on DMPC liposomes by overnight incubation. The receptor affinity of the enkephalin derivatives became significantly higher upon immobilization on liposomes. The highest affinity was obtained for the delta receptor by Enk6D immobilized on DMPC liposomes. This affinity is higher than that of enkephalinamide. Neurotensin derivatives coimmobilized with large amounts of Enk3D on the DMPC liposomes show higher affinity than the neurotensin derivatives immobilized alone. The effect of Enk3D on the receptor affinity of the coimmobilized neurotensin derivative disappeared by the addition of [Ala2, MePhe4, Glyol5]enkephalin (DAGO). Therefore, the receptor affinity of a peptide hormone is altered by immobilization on DMPC liposomes and by coimmobilization with other peptide hormones. It was confirmed by fluorescent microscopy that the multivalent ligand system binds to receptors without release of the bound ligands from DMPC liposomes.

Animals↗

Leptin receptor expression increases in placenta, but not hypothalamus, during gestation in Mus musculus and Myotis lucifugus.

In addition to effects on appetite and metabolism, the hormone leptin is required for reproduction in mammals. Maternal plasma leptin is increased above non-pregnant levels in all mammals thus far examined, including humans. The increase in plasma leptin appears to result in part from upregulation of adipose leptin secretion (e.g., in mice), or from production and secretion of leptin from the placenta (e.g., in humans and some bats). The placenta may also modulate maternal leptin levels via production of a plasma leptin-binding protein (mice, humans). Thus, the placenta plays a coordinating role in regulation of maternal leptin during pregnancy. In this study, the hypothesis that the placenta is also a target organ for leptin in diverse taxa was tested by examining the expression of leptin receptors (Ob-R) in placentae from species of distantly related mammalian taxa, Mus musculus (the laboratory mouse) and Myotis lucifugus (the little brown myotis, also called the little brown bat). A partial sequence of M. lucifugus Ob-R cDNA was first obtained and found to share approximately 78-88% homology at the nucleotide level with known mammalian Ob-R cDNAs. Using probes and primers designed from this sequence, receptor expression was detected in numerous tissues of M. lucifugus, including placenta, which expressed two major receptor isoforms as judged by molecular size. In both species, Ob-R mRNA expression in placenta significantly increased from early to late gestation. Expression of Ob-R mRNA was not affected by cAMP treatment in vitro. The increase in Ob-R mRNA expression in placenta was specific, since Ob-R mRNA expression did not change during gestation in either species in hypothalamus, the major site of the central actions of leptin. Thus, Ob-R is expressed in placenta throughout gestation in mice and bats, and its expression increases over the course of gestation, which raises the possibility that leptin may exert temporally distinct effects on placental growth or function throughout gestation. Because similar placenta-specific changes in leptin receptor expression occurred in species from distantly related mammalian taxa which collectively comprise approximately 70% of all known mammalian species, it is possible that placental actions of leptin are conserved across mammals, even in those species (such as the Swiss-Webster strain of mouse) in which the placenta does not itself produce leptin.

Animals↗

Mediator-free amperometric determination of toxic substances based on their inhibition of immobilized horseradish peroxidase.

We have demonstrated the feasibility of quantitatively detecting selected toxic materials through their inhibitory effect on an enzyme electrode that utilizes colloidal gold-immobilized horseradish peroxidase and does not require a mediator. Quantitative detection of azide, cyanide, thiourea, sulfide, and dichromate is demonstrated. The sensitivity and inhibition kinetics for this immobilized enzyme electrode are found to be different from those observed previously for homogeneous horseradish peroxidase. Possible reasons for this difference are discussed. Due to the availability of a large number of enzymes and their toxic inhibitors, this work based on immobilized enzyme inhibition coupled to an electrode surface significantly broadens the possible applications of biosensors and offers alternative methods for toxic substance determination.

Anions↗

Structure of 5' regions and expression of phenobarbital-inducible rabbit cytochrome P450IIC genes.

To analyze phenobarbital-inducible genes in the P450IIC subfamily, fragments of rabbit genomic DNA containing portions of the P450IIC1 and P450IIC4 genes were isolated and the DNA sequences of the 5'-flanking regions and exons were determined and compared to that of the P450IIC2 gene. The sequences have consensus TATA motifs about 20 bp from the mRNA initiation sites as determined by single-strand nuclease mapping and primer extension. Sequences similar to those for proposed liver-specific regulatory factors, HNF-1 and CCAAT, are found in the P450 5'-flanking regions. A glucocorticoid response element is present in the P450IIC2 gene but is not conserved in P450IIC1 or P450IIC4. Other sequences similar to binding sites for AP-1, the octamer binding proteins, and SPH-1 are present. Except for the TATA motif, none of the potential regulatory sequences was conserved at the same location in the different genes. The P450IIC1 and P450IIC2 genes exhibited high similarity detectable by dot matrix analysis throughout the 700 bp of sequenced 5'-flanking region while the P450IIC4 gene exhibited high similarity to both P450IIC1 and P450IIC2 only for about -150 nucleotides from the RNA initiation site. Southern analysis using probes from the 5' region of the P450IIC4 gene suggests that there are at least three closely related members in the P450IIC4 subgroup in agreement with previous studies. After phenobarbital treatment, levels of P450IIC4 mRNA increased about fourfold, as measured by dot blot hybridization with a P450IIC4-specific oligonucleotide probe or by single-strand nuclease mapping of the 5' end of the mRNA, indicating that the P450IIC4 gene characterized in this study is responsive to phenobarbital. Phenobarbital treatment of rabbits increased in vitro transcription of RNA for both the P450IIC1/2 and P450IIC4 gene subgroups but only slightly and transiently for the constitutive P450IIC3 gene.

Amino Acid Sequence↗

Toxicity of beta-carotene and its exacerbation by acetaldehyde in HepG2 cells.

In rats and baboons, the hepatotoxicity of chronic ethanol consumption is exacerbated by beta-carotene feeding, but the mechanism of this adverse effect is unknown. In this study, the toxicity of beta-carotene and acetaldehyde was documented by the MTT test (an assay of reduction of tetrazolium to formazan) and by lactate dehydrogenase (LDH) leakage. In HepG2 cells, beta-carotene or acetaldehyde inhibited mitochondrial reduction function as indicated by a decrease of the MTT test. beta-Carotene was inhibitory at very low concentration, in a dose-dependent manner. The combination of these two compounds resulted in an additive effect. Acetaldehyde increased LDH leakage from the HepG2 cells into the medium, whereas beta-carotene by itself did not show such an effect, but it exacerbated the toxicity of acetaldehyde when combined. In addition, this study showed that acetaldehyde and beta-carotene inhibited each other's clearance from the medium, which suggests that these two chemicals may share, at least in part, a common metabolic pathway (possibly via aldehyde dehydrogenase) in the cells, and that a competitive inhibition may exist. In conclusion, this preliminary study indicates that beta-carotene is toxic to hepatocytes, especially when combined with acetaldehyde, the metabolite of ethanol.

Acetaldehyde↗

Pyoderma gangraenosum caused by Rhizopus arrhizus.

A rare case of pyoderma gangraenosum caused by Rhizopus arrhizus is reported. The patient, a 50-year-old male farmer, was admitted to hospital complaining of gangrening and festering of the right upper arm with severe pain for nearly 2 months. A lesion was found on the inside of right upper arm. The central skin part of the lesion became black dry gangrenous, the periphery was deeply ulcerated with yellow-green pus. The necrotic crust, biceps, triceps and vessels inherited a histopathologically proven fungal infection. The fungus isolated was identified as Rhizopus arrhizus. The infection was successfully treated with itraconazole.

Humans↗

Function of estrogen receptor isoforms alpha and beta in endometrial carcinoma cells.

The aim of this study was to explore how to modulate the expression of estrogen receptors (ER) alpha and beta and to verify the role of ERalpha and beta in relationship to estrogen and tamoxifen (TAM). A series of oligodeoxyribonucleotides (ODN) corresponding to regions of the ERalpha or beta was tested in human endometrial cancer cell lines (HEC-1B). The change in HEC-1B proliferation in response to 17beta-estradiol (E(2)) and TAM under the impact of antisense ODN was studied. The results of the study are as follows: 1) transfection with antisense ODN significantly inhibited ERalpha and ERbeta protein production, 2) the cells lost the ability to proliferate in response to E(2) after transfection with ERalpha antisense ODN especially at 24, 48, and 72 h. There was no obvious change in response to E(2) in HEC-1B cell lines that were transfected with ERbeta antisense ODN, and 3) after transfection with ERalpha antisense ODN, HEC-1B cells lost the ability to proliferate in response to TAM at 48 h. This inhibition was also observed after transfection with ERbeta antisense ODN at 24 h. ERalpha may be the primary receptor in the proliferation of HEC-1B cells in response to E(2). Both ERalpha and ERbeta are involved in the agonist impact of TAM on endometrial cancer cells.

Cell Proliferation↗

Different effect of ATP on ANP receptor guanylyl cyclase in spontaneously hypertensive and normotensive rats.

AIM: Natriuretic peptide receptor A (NPR-A) is the main physiological receptor for atrial natriuretic peptide (ANP). Maximal activation of NPR-A guanylyl cyclase (GC) requires ANP binding and ATP interaction with a putative cytoplasmic site. This study investigates the regulatory effect of ATP on GC-coupled NPR-A activity in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). METHODS: Cyclic GMP production and competitive inhibition of [(125)I]ANP(1-28) binding were performed in solubilized glomerular and papillary renal membranes. RESULTS: Here, we report that incubation of renal glomerular and papillary membranes with ATP induced a concentration-dependent increase in basal and ANP(1-28)-stimulated GC activity that was significantly greater in SHR than in age-matched WKY. ATPgammaS was more effective than ATP and induced a greater stimulation of cGMP production in SHR than in WKY. In contrast, in solubilized membranes ATP exerted an inhibitory role on basal and ANP(1-28)-induced GC activity, suggesting that an accessory protein is required for ATP-induced GC activation. ATP increases NPR-A affinity for ANP(1-28) and decreased B(max) in crude and solubilized membranes. Kinetic analysis of GC-coupled NPR-A revealed that ATP reduced the Km and increased the V(max), an effect that was greater in SHR. CONCLUSION: Our observations indicate that ATP exerts a greater net effect on NPR-A in SHR than in WKY, which might explain the greater rate of cGMP production observed in SHR compared to WKY.

Adenosine Triphosphate↗

Characterization of B2-bradykinin receptors in rabbit principal cells of the collecting duct.

Bradykinin (BK) plays a key role in collecting duct functions. Using an established line of principal cells of the rabbit collecting duct (R.C. SV3), we examined the characteristics of the BK receptors in these cells. [3H]-BK bound specifically to R.C. SV3. Saturation binding analyses allowed KD (968 +/- 232 pM) and Bmax values (356 +/- 43 fmol/mg protein) to be calculated. Competitive displacement of [3H]-BK was observed with Hoe-140, a specific type 2 BK receptor (BKR-2) antagonist, but not with des arg9-BK, a BKR-1 agonist. The presence of BKR-2 was confirmed by the reverse-transcription polymerase chain reaction technique. BK stimulated cytosolic calcium and inositol phosphate formation in a dose-dependent manner (from 1 nM to 1 microM). BK also inhibited the arginine vasopressin dependent increase of cyclic adenosine monophosphate. This effect could not be related to the production of prostaglandin E2. These results demonstrate the presence of high-affinity BKR-2 in the principal cells of the rabbit collecting duct that are linked to phospholipase C activity and are involved in arginine vasopressin related regulatory loops.

Animals↗

Molecular analysis to assign parental origin and distinguish de novo i(21q) from t(21q21q) in two Down syndrome fetuses.

OBJECTIVE: We sought to determine the origin of two prenatal cases of chromosome 21 rearrangements not amenable to clarification by conventional cytogenetic methodology. METHODS: Hypervariable repeat polymorphisms (chromosome 21) were used to determine the type of structural rearrangement and the parental origin of the rearranged chromosome. The repeats used were highly polymorphic and located very close to the centromere; thus, the likelihood of differences among the parental alleles and overall informativeness were increased. RESULTS: The rea(21q21q) chromosomes were identified as a Robertsonian translocation in one fetus and an isochromosome in the other. The extra chromosome material was found to be maternal in origin in both cases. CONCLUSION: The ability to clarify the origin of abnormal chromosomal rearrangements provides valuable information concerning possible mechanisms of aneuploidy, as well as clinical data that may have an impact in assessing a patient's risk for abnormal offspring.

Chromosomes, Human, Pair 21↗