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Biomedical subjects

H Zhou

Publications and source records attributed to H Zhou.

At least 451 records · Page 25Linked to original sources

[Sequence analysis of 25S rDNA from Chinese medicinal plant duzhong Eucommia ulmoides Oliv].

OBJECTIVE: To provide new molecular data for the identification of the Chinese medicinal plant Duzhong (Eucommia ulmoides). METHOD: Sequencing and analyzing the 25S rDNA gene(rDNA) 5' terminal region. RESULT: More than 300 nucleotides of 25S rDNA 5' terminal region were determined, and the specific nucleotides can be used for the identification of this medicinal plant. CONCLUSION: This sequence analysis may serve as a basis for preparing the specific rDNA probe.

DNA, Plant↗

[Simulated experiment of hemodynamics changes in aorta during high energetic trauma through abdomen].

In order to study the mechanism of remote effect of missile wound, we designed and carried out a simulated experiment. The change of hemodynamics in aorta was examined with a pressure transducer during gunshot and then calculated. The results revealed superhigh pressure, high speed of pressure rising, accelerated velocity of blood flow, substantial pressure difference and profuse blood flow in aorta during gunshot.

Abdominal Injuries↗

[Selection of drug-labelled Bacillus sphaericus and studies on transformation and expression of foreign DNA].

NTG was used to make chemical mutation for Bacillus sphaericus, RifR and SmR labelled strains were selected, which could resist drug as much as 100 u/ml. The resistance to drug was stably inherited. The RifR strain was used as recipient and the plasmid containing the lysostaphin gene was transfered into it by protoplasts. Results showed that the lysostaphin gene could be expressed stably at high level in Bacillus sphaericus and the lysostaphin activity was about 122 u/ml medium after shaking culture.

Bacillus↗

[Supercritical-CO2 fluid extraction of Allium stativum oils].

Effective constituents from bulb of Allium stativum were extracted by supercritical-CO2 fluid. These constituents were analyzed by GC-MS. The results showed that oils from SFE-CO2 contained 12 components, two of them were first obtained from the plant.

Allium↗

[Serum soluble interleukin-2 receptor levels in uveitis].

PURPOSE: To investigate the relationship between serum SIL-2R levels and uveitis. METHODS: SIL-2R levels were measured in sera of 64 patients with active uveitis by ELISA assay, 61 healthy subjects as control. RESULTS: Serum SIL-2R levels in the patients with active uveitis were significantly higher than that in the controls, but there were no significant difference among anterior uveitis, intermediate uveitis, Behcet disease and Vogt-Koyanagi-Harada syndrome. After therapy the serum SIL-2R levels were obviously decreased. CONCLUSION: SIL-2R Levels in serum correlate with activity of uveitis.

Adolescent↗

Parathyroid-hormone-related protein in sarcoidosis.

Parathyroid-hormone-related protein (PTHrP) is the main mediator of the humoral hypercalcemia of malignancy. It is also detected in many normal adult and fetal tissues. Altered calcium metabolism occurs in sarcoidosis, and two cases of sarcoidosis with hypercalcemia and elevated plasma PTHrP are described. An archival study of 20 lymph node biopsies with the pathological diagnosis of sarcoidosis was performed. Immunohistochemistry using a polyclonal antiserum to human PTHrP and in situ hybridization using a riboprobe to human PTHrP were performed on the lymph node biopsies. Immunohistochemistry for PTHrP was also performed on the biopsies from the two cases with elevated plasma levels. Immunohistochemical analysis detected PTHrP in macrophages within granulomata in 17 of the 20 (85%) biopsies. In situ hybridization detected a positive signal for messenger RNA in the granulomata of 11 of 19 (58%) biopsies. PTHrP immunoreactivity and PTHrP gene expression are present in sarcoid granulomata. PTHrP may contribute to the hypercalcemia of sarcoidosis.

Adult↗

The -4 kilobase promoter region of the winged helix transcription factor HNF-3alpha gene elicits transgene expression in mouse embryonic hepatic and intestinal diverticula.

Murine hepatocyte nuclear factor-3alpha (HNF-3alpha) protein is a member of a large family of developmentally regulated transcription factors that share homology in the winged helix/fork head DNA binding domain and participate in embryonic pattern formation. HNF-3alpha also mediates cell-specific transcription of genes important for the function of hepatocytes, intestinal, pancreatic and bronchiolar epithelium. We have previously determined that -520 nucleotides upstream of the rat HNF-3alpha gene were sufficient to elicit hepatoma-specific expression in transfection assays and reported on a novel HNF-3alpha expression pattern in the renal pelvis urothelium of the embryonic and adult kidney. We also showed that retinoic acid mediated activation of the HNF-3alpha gene required -4 kb of the HNF-3alpha promoter region in F9 teratocarcinoma transfections. In order to determine regulatory sequences mediating the HNF-3alpha cellular expression pattern in developing mouse embryos, we created transgenic mice bearing the -4 kb HNF-3alpha promoter region driving expression of the beta-galactosidase transgene. Embryonic analysis of two transgenic mouse lines demonstrated that the -4 kb HNF-3alpha promoter sequences were sufficient to elicit transgene expression in the developing liver, intestine, esophagus, nasal epithelial cells and floorplate of the neurotube, but not in the mesodermal notochord or in the lung bud. One of the transgenic lines also exhibited proper expression in the mesonephric ducts and metanephric diverticulum, suggesting that the -4 kb HNF-3alpha promoter region contained a subset of the regulatory sequences necessary for HNF-3alpha expression in the developing kidney.

Animals↗

Prothrombin and its derivatives stimulate motility of melanoma cells.

Several studies indicated that activation of the clotting system may promote the growth and the invasive behavior of tumor cells. In the present study, we evaluated the migratory response of various melanoma cell lines to several clotting factors and prothrombin derivatives (thrombin, fragment 1, fragment 2 and kringle 1 fragment). Prothrombin, thrombin and fragment 1 stimulated chemotaxis of the murine (K-1735 M2, X21) and human A375 (SM) melanoma cell lines. Prothrombin and prothrombin fragment 1 showed their maximal chemotactic activity at 0.5 approximately 1 microM. Chemotaxis induced by thrombin was inhibited by hirudin, but not that induced by prothrombin or fragment 1. Other clotting proteins and the fragment 2 and kringle 1 fragment of prothrombin did not elicit chemotactic activity. Checkerboard analysis indicated that motility was directional with a significant chemokinetic component. The K-1735 M2 cells also migrated in a concentration-dependent manner to substratum-bound insoluble prothrombin, thrombin or fragment 1. Ligand binding assays showed that both prothrombin and fragment 1 bound to K-1735 M2 cells with apparent Kds of 0.5 microM. This binding was inhibited by an excess concentration of unlabeled prothrombin and fragment 1 but not by similar concentrations of other prothrombin fragments. These findings suggest that prothrombin and its fragment 1 exert chemotactic activity on melanoma cells by different mechanisms and different binding sites from that induced by thrombin.

Animals↗

Covalent attachment of ethidium to DNA results in enhanced topoisomerase II-mediated DNA cleavage.

The classic DNA intercalator, ethidium, was used to probe the effects of (i) intercalation and (ii) covalent modification of the DNA on the catalytic activity of topoisomerase II. Ethidium bromide, which binds reversibly to DNA via intercalation, does not stimulate topoisomerase II-mediated DNA cleavage at concentrations up to 100 microM, indicating that the intercalative binding of this molecule to DNA is not sufficient to alter the activity of the enzyme. In contrast, covalent attachment of the photoreactive ethidium analog to DNA resulted in marked enhancement of topoisomerase II-mediated single- and double-stranded DNA cleavage. This increase in DNA cleavage was observed at very low drug binding densities (<1 drug per 10-80 base pairs) which correspond to nanomolar concentrations, as compared with other topoisomerase II poisons such as etoposide or m-AMSA which require micromolar concentrations to elicit comparable DNA cleavage levels. Over the past decade, topoisomerase II has been an important target for a variety of clinically relevant anticancer agents due to the abilities of these agents to convert this enzyme to a cellular toxin resulting in an increase in the levels of enzyme-mediated DNA breaks. Modification of DNA by covalently attaching a DNA-targeting intercalating agent (i.e., ethidium bromide) resulted in a marked shift of the cleavage/religation equilibrium of the enzyme toward the cleaved state "poison" topoisomerase II as observed by the enhancement in single- and double-stranded cleavage; thus, key insight was gained into the mechanism(s) through which DNA binding agents may influence the catalytic properties of topoisomerase II. These data demonstrate that conversion of a reversible ethidium-DNA complex to an irreversible adduct results in the transformation of an ineffective intercalating drug into a potent topoisomerase II-targeted agent. Finally, they provide support for the recently proposed "positional poisoning model" for the actions of DNA lesions and anticancer drugs on the type II enzyme.

Animals↗

Calcitonin receptors, bone sialoprotein and osteopontin are expressed in primary breast cancers.

Several human breast cancer cell lines express the calcitonin receptor (CTR), but this has not been demonstrated previously in clinical breast cancers. We examined 18 primary breast cancers by reverse transcription-PCR, for expression of CTR and of the bone proteins osteopontin (OPN) and bone sialoprotein (BSP). OPN and CTR were expressed by each of the tumours, and 7 (39%) additionally expressed an alternate form of CTR, whilst BSP was expressed by 13 tumours (72%). In situ hybridisation confirmed that expression of OPN and CTR was confined to the tumour cells. Expression of CTR, BSP and OPN may prove to be a useful marker for breast cancers, and their role in the homing of breast cancer cells to bone remains to be investigated.

Breast Neoplasms↗

Effect of weight, sex, age, clinical diagnosis, and thromboplastin reagent on steady-state intravenous heparin requirements.

BACKGROUND: There is a significant direct relationship between steady-state intravenous heparin dose requirements and total body weight. Less is known about whether sex, age, clinical diagnosis, and the thromboplastin used to measure the activated partial thromboplastin time (aPTT) affect heparin dose requirements. METHODS: Four cohorts of patients treated with intravenous heparin were gathered from 3 hospitals: 2 cohorts with deep vein thrombosis (DVT) and 2 cohorts with coronary artery disease (CAD). For each clinical diagnosis, half the patients were monitored using one aPTT reagent and the remainder were monitored using a second reagent. Heparin doses and aPTT measurements were recorded, and the dose necessary to achieve an aPTT ratio of 2.0 was calculated using a computer software program. RESULTS: We analyzed the records of 340 patients: 165 with DVT and 175 with CAD. Using analysis of variance, there was a significant difference in the steady-state heparin requirements among patients with DVT compared with patients with CAD (P < .001). For each clinical diagnosis, the use of a different thromboplastin reagent did not affect heparin dose requirements (P > .42). Linear regression modeling disclosed that the steady-state heparin dose for patients with DVT was a function of weight plus an effect modifier involving weight and age, whereas for patients with CAD there was only a weak relationship with weight. CONCLUSIONS: Steady-state heparin dose requirements were significantly different in patients with DVT compared with patients with CAD, suggesting that different dosing nomograms are needed for each condition. For patients with DVT, the accuracy of the initial heparin dose estimate may be improved by considering the patient's age and weight.

Aged↗

Mutations at codon 249 of p53 gene in human hepatocellular carcinomas from Tongan, China.

Codon 249 (exon 7) of the putative tumor suppressor gene p53 is a mutational hot-spot for hepatocellular carcinoma (HCC) but not other tumors. DNA samples from primary HCC patients from Tongan, an area of high HCC incidence in China (> 40 per 100,000 population), were analyzed for specific mutations in codon 249 of the p53 gene using polymerase chain reaction (PCR)/restriction-digest methods and direct DNA sequencing. Seven of the 21 samples screened were found to have a point mutation at the third base position of codon 249 (AGG to AGT). The result is consistent with previous reports that the G-->T transversion is positively associated with the level of dietary aflatoxin B1 (AFB1) contamination, which has been implicated as one of the risk factors in Tongan area. Of the 7 HCC patients that contained the codon 249 point mutation, one was hepatitis B virus (HBV)-negative. This is only the second documentation of an HCC patient harboring the p53 codon 249 mutation, who was HBV-negative.

Adult↗

A tool for analyzing and annotating genomic sequences.

We describe a tool for analyzing and annotating large genomic sequences containing introns. The analysis and annotation tool (AAT) includes two sets of programs, one for comparing the query sequence with a protein database and the other for comparing the query with a cDNA database. Each set contains a fast database search program and a rigorous alignment program. The database search program quickly identifies regions of the query sequence that are similar to a database sequence. Then the alignment program constructs an optimal alignment for each region and the database sequence. The alignment program also reports the coordinates of exons in the query sequence. Pairwise alignments of the query sequence with protein and cDNA database sequences are combined into multiple sequence alignments, which provide a view of all protein and cDNA sequences matching a query region. On a data set of 570 DNA sequences, AAT identified 94% of coding nucleotides correctly and 74% of exons exactly. Results of analyzing a human BAC sequence with the AAT tool are also presented. The AAT tool reduces the labor-intensive work of locating the exons of the query sequence and improves the process of defining intron-exon boundaries by using the wealth of available protein and cDNA data.

Amino Acid Sequence↗

Biochemical and antiproliferative properties of 4-[ar(alk)ylamino]pyridopyrimidines, a new chemical class of potent and specific epidermal growth factor receptor tyrosine kinase inhibitor.

The tyrosine kinase inhibitors PD 69896, 153717, and 158780, which belong to the chemical class 4-[ar(alk)ylamino]pyridopyrimidines, have been characterized with respect to enzymology, target specificity, and antiproliferative effects in tumor cells. These compounds were competitive inhibitors with respect to ATP against purified epidermal growth factor (EGF) receptor tyrosine kinase and inhibited EGF receptor autophosphorylation in A431 human epidermoid carcinoma with IC50 values of 2085, 110, and 13 nM, respectively. Onset of inhibition was immediate once cells were exposed to these compounds, whereas recovery of receptor autophosphorylation activity after the cells were washed free of the compound was dependent on inhibitory potency. Thus, full activity returned immediately after removal of PD 69896 but required 8 hr after exposure to PD 158780. PD 158780 was highly specific for the EGF receptor in Swiss 3T3 fibroblasts, inhibiting EGF-dependent receptor autophosphorylation and thymidine incorporation at low nanomolar concentrations while requiring micromolar levels for platelet-derived growth factor- and basic fibroblast growth factor-dependent processes. PD 158780 inhibited heregulin-stimulated phosphorylation in the SK-BR-3 and MDA-MB-453 breast carcinomas with IC50 values of 49 and 52 nM, respectively, suggesting that the compound was active against other members of the EGF receptor family. The antiproliferative effects of this series of compounds against A431 cells correlated precisely with the inhibitory potency against EGF receptor autophosphorylation. PD 158780 reduced clone formation in soft agar of fibroblasts transformed by EGF, EGF receptor, or the neu oncogene but not ras or raf, further demonstrating its high degree of specificity. Finally, this compound was active against clone formation in several breast tumors having different expression patterns of the erbB family, indicating an anticancer utility in tumors expressing these receptors.

Carrier Proteins↗

Sequential assignments and secondary structure of the RNA-binding transcriptional regulator NusB.

The NusB protein is involved in transcriptional regulation in bacteriophage lambda. NusB binds to the RNA form of the nut site and along with N, NusA, NusE and NusG, stabilizes the RNA polymerase transcription complex and allows stable, persistent antitermination. NusB contains a 10 residue Arg-rich RNA-binding motif (ARM) at the N-terminus but is not sequentially homologous to any other proteins. In contrast to other known ARM-containing proteins, NusB forms a stable structure in solution in the absence of RNA. NMR spectroscopy was used to determine that NusB contains six alpha-helices: R10-Q21, 127-F34, V45-L65, Q79-S93, Y100-F114 and D118-L127. The structure of NusB makes it a member of a newly emerging class of alpha-helical RNA-binding proteins.

Amino Acid Sequence↗

Estimating the mean hazard ratio parameters for clustered survival data with random clusters.

We consider a latent variable hazard model for clustered survival data where clusters are a random sample from an underlying population. We allow interactions between the random cluster effect and covariates. We use a maximum pseudo-likelihood estimator to estimate the mean hazard ratio parameters. We propose a bootstrap sampling scheme to obtain an estimate of the variance of the proposed estimator. Application of this method in large multi-centre clinical trials allows one to assess the mean treatment effect, where we consider participating centres as a random sample from an underlying population. We evaluate properties of the proposed estimators via extensive simulation studies. A real data example from the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial illustrates the method.

Adult↗

Alzheimer presenilins in the nuclear membrane, interphase kinetochores, and centrosomes suggest a role in chromosome segregation.

Mutations in two related genes, presenilin 1 and 2, account for most early-onset familial Alzheimer's disease. Although structural features indicate that the presenilins are membrane proteins, their function(s) is unknown. We have localized the presenilins to the nuclear membrane, its associated interphase kinetochores, and the centrosomes-all subcellular structures involved in cell cycle regulation and mitosis. The colocalization of the presenilins with kinetochores on the nucleoplasmic surface of the inner nuclear membrane, together with other results, suggests that they may play a role in chromosome organization and segregation, perhaps as kinetochore binding proteins/receptors. We discuss a pathogenic pathway for familial Alzheimer's disease in which defective presenilin function causes chromosome missegregation during mitosis, resulting in apoptosis and/or trisomy 21 mosaicism.

Alzheimer Disease↗

Sorption/desorption of radioactive contaminants by sediment from the Kara Sea.

To understand the long term impact of the disposal of radioactive waste on the Kara Sea, partition coefficients (Kd) for several important radionuclides, the mineralogy of the sediment, and the relationship of Kd to liquid-to-solid ratio were quantified. Sediment was obtained from four locations in the Kara Sea area. Slow sorption kinetics were observed for 85Sr, 232U, 125I and 99Tc, whilst sorption was rapid (less than 50 h to steady-state) for 137Cs, 210Pb, and 241Am. Partition coefficients (Kd) were determined using batch type experiments and sorption isotherms which were developed for 85Sr, 99Tc, 125I, U and 137Cs. Partition coefficients for 137Cs were approx. 350 ml/g for sediment from the Trough and 180 ml/g for Stepovogo Fjord. This difference may be caused by the lower fraction of expandable clay in sediment from the fjord. Uptake of 85Sr, 99Tc, 125I, and U were all similar for both locations, with Kd values averaging 4, 3, 17 and 60 ml/g, respectively. The Kd for 137 Cs varied non-linearly from 40 to 3800 ml/g as the liquid-to-solid ratio varied from 3.4 to 6500, but only when the sorption capacity was high compared to the mass of 137Cs in the closed system of the experiment. Under identical conditions, sediment with lower Kd values showed no effect. Oxidation of sediment effectively desorbed 99Tc from the solid phase, whilst it caused increased uptake of 85Sr and U. In sequential rinses with fresh seawater, desorption was limited to 60% of 137Cs and 85Sr, and 35% of uranium.

Absorption↗