Biomedical subjects
Publications and source records attributed to J Dai.
The crude extract of the broth of Aspergillus ochraceus was found to inhibit the final stage of polyprotein processing during hepatitis C virus replication. Bioassay-guided fractionation led to the isolation of the known compound mellein as the active component of the extract. Also isolated were circumdatin F and a new alkaloid, circumdatin G. The structure of circumdatin G was determined by spectroscopic analysis.
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We report the cloning and characterization of a novel human hydroxysteroid dehydrogenase like gene (HSDL1) located on human chromosome 16q24.2. The HSDL1 cDNA is 3407 base pair in length, encoding a 309 amino acid polypeptide related to human 17beta-HSD3. Northern blot reveals that the HSDL1 is highly expressed in testis and ovary. In situ hybridization indicates that the expression of HSDL1 is predominantly increased in the prostate cancer tissue compared with the normal prostate tissue, which suggests that the gene expression is important to the arising of prostate cancer.
There is increasing evidence that antiproteases are able to affect the inflammatory response. To further examine this question, we administered human alpha-1-antitrypsin (alpha1AT) or a synthetic metalloprotease inhibitor (RS113456) to C57 mice followed by a single intratracheal dose of quartz, a dust that evokes a marked, lasting, polymorphonuclear leukocyte (PMN) infiltrate. At 2 hours after dust administration, both antiproteases completely suppressed silica-induced PMN influx into the lung and macrophage inflammatory protein-2 (MIP-2)/monocyte chemotactic protein-1 (MCP-1) (neutrophil/macrophage chemoattractant) gene expression, partially suppressed nuclear transcription factor kappaB (NF-kappaB) translocation, and increased inhibitor of NF-kappaB (IkappaB) levels. By 24 hours, PMN influx and connective tissue breakdown measured as lavage desmosine or hydroxyproline were still at, or close to, control levels after antiprotease treatment, and increases in NF-kappaB translocation and MIP-2/MCP-1 gene expression were variably suppressed. At both time points, neither agent prevented silica-induced increases in amount of whole lung MIP-2 or MCP-1 protein, but both did prevent increases in whole lung intercellular adhesion molecule-1 (ICAM-1) at 24 hours. Inactivating the alpha1AT by oxidation to the point that it no longer possessed antiproteolytic properties did not affect its ability to suppress inflammation. Both antiproteases also prevented the silica-induced acute inflammatory response in mice with knocked out genes for macrophage metalloelastase (MME -/-), mice that develop inflammation, but not connective tissue breakdown, and the pattern of alpha1AT breakdown fragments was identical in control and MME -/- animals. These findings suggest that, in this model of acute PMN mediated inflammation, a serine protease inhibitor and a metalloprotease inhibitor have similar anti-inflammatory properties, that inflammation is not mediated by proteolysis with generation of chemotactic matrix fragments, and that classic antiproteolysis (complexing of protease to antiprotease) probably does not play a role in suppression of inflammation. The antiproteolytic effects of these agents do not seem to be mediated by protection of endogenous alpha1AT.
OBJECTIVE: Observe the growth pattern of infants from birth to 18 months. METHODOLOGY: A prospective study was conducted from 1994 to 1996 in urban and township-rural areas of Guangdong Province, southern China, recruiting 568 and 257 newborn infants, respectively. Anthropometric data was collected at birth, 1.5, 4, 5, 6, 8, 10, 12, 15, and 18 months. RESULTS: The urban infants at birth had Z-scores of weight for age (WAZ), height for age (HAZ) and weight for height (WHZ) below the National Center for Health Statistics (NCHS) median (P < 0.01). However, from 1.5 to 4 months, the WAZ and WHZ scores were above (P < 0.01), but by 7 months fell and remained at - 0.7 to - 0.8 SD below the NCHS median (P < 0.01). HAZ scores improved after birth, were at the NCHS median to 8 months (P = NS), and then decreased to 0.2-0.4 SD below the NCHS median (P < 0.01). Compared with the urban infants, the township-rural infants were lighter and shorter throughout the first 18 months of life, and from 8 months of age, were - 1 SD or more below the NCHS median. CONCLUSIONS: Growth retardation was found in this sample of Chinese infants. The magnitude of growth retardation was greater for infants in the township-rural area compared with those in the urban area.
Stereotactic localization of an intracranial lesion by computed tomography or magnetic resonance imaging requires the use of a head frame that is fixed to the skull of the patient. To such head frames are attached either N-shaped or V-shaped localization rods. Because of patient positioning, the transverse imaging slices may not be parallel to the frame base; a coordinate transformation algorithm that takes this possibility into consideration is crucial. Here we propose such an algorithm for a head frame with V-shaped localization rods. Our algorithm determines the transformation matrix between the image coordinate system of a transverse image and the frame coordinate system. The determining procedure has three steps: (a) calculation of the oblique angles of a transverse image relative to the head frame and calculation of the image magnification factor; (b) determination of the coordinates of four central markers in both coordinate systems; and (c) determination of the 3 x 3 transformation matrix by using the coordinates of the four markers. This algorithm is robust in principle and is useful for improving the accuracy of localization.
This study verifies the concept of the super-omni wedge by validating its equations for effective wedge orientation and wedge angle and by comparing the dose distributions it produces with those produced by other wedge techniques. To validate the equations, we calculated dose distributions for 20 combinations of wedge orientations and wedge angles: we then determined the differences between the wedge orientations and angles predicted by the equations and those calculated by a three-dimensional treatment-planning system. To compare the super-omni wedge concept with other techniques, we calculated the dose and position differences between the dose distributions produced by the super-omni wedge concept and those produced by other wedge techniques. The error of wedge orientations ranged from -0.5 degrees to 0.4 degrees, and that of wedge angles ranged from -0.6 degrees to 1.7 degrees. The dose distributions produced by the super-omni wedge were similar and therefore equivalent to those produced by other wedge techniques. Serving as an intermediate step in treatment-planning optimization. the super-omni wedge is a reliable method for producing wedged dose distributions with arbitrary wedge orientations and wedge angles.
OBJECTIVES: To investigate the anticancer activities of Chinese leek (Allium tuberosum Rottler; [CL]). DESIGN: Fresh CL was extracted and reconstituted in phosphate-buffered saline. The in vitro antiproliferation activities of the extract were tested with two murine cancer cell lines and four human cancer cell lines. The in vivo anticancer effects were tested in C57BL mice with lung metastases of B16-F10 melanoma. The mice were inoculated with B16-F10 melanoma cells by intravenous (IV) injection on day 1. CL extract was given on days 6-8 by either IV injection or oral gavage. The lung metastases were examined on day 16. RESULTS: The extract inhibited the in vitro growth of all six cancer cell lines studied. The dose-response curves were sigmoidal with IC50 (50% inhibition concentrations) in the range of 2.5-13.0 mg of raw material per milliliter for the six cancer cell lines. At the CL concentration of 8-100 mg of raw material per milliliter, all the cells underwent apoptosis, and no live cells were left after being exposed to CL for 4-6 hours. Typical apoptosis-specific cell morphology changes were observed under a microscope. The induction of cancer cell apoptosis by CL extract was further verified by the DNA ladder assay. Treatment with a daily oral dose of the extract (equivalent to 2.5 or 12.5 mg of raw material per gram of body weight) reduced the B16-F10 melanoma lung metastatic colonies in mice by 40% (p < 0.03). IV injection of the extract (equivalent to 1.25 or 6.25 mg of raw material per gram of body weight) did not show any effect. CONCLUSIONS: CL extract inhibited cancer cell growth and induced apoptosis in vitro. Oral administration of CL extract significantly reduced lung metastases in the present animal model.
This paper proposes a sequencing algorithm for intensity-modulated radiation therapy with a multileaf collimator in the static mode. The algorithm aims to minimize the number of segments in a delivery sequence. For a machine with a long verification and recording overhead time (e.g., 15 s per segment), minimizing the number of segments is equivalent to minimizing the delivery time. The proposed new algorithm is based on checking numerous candidates for a segment and selecting the candidate that results in a residual intensity matrix with the least complexity. When there is more than one candidate resulting in the same complexity, the candidate with the largest size is selected. The complexity of an intensity matrix is measured in the new algorithm in terms of the number of segments in the delivery sequence obtained by using a published algorithm. The beam delivery efficiency of the proposed algorithm and the influence of different published algorithms used to calculate the complexity of an intensity matrix were tested with clinical intensity-modulated beams. The results show that no matter which published algorithm is used to calculate the complexity of an intensity matrix, the sequence generated by the algorithm proposed here is always more efficient than that generated by the published algorithm itself. The results also show that the algorithm used to calculate the complexity of an intensity matrix affects the efficiency of beam delivery. The delivery sequences are frequently most efficient when the algorithm of Bortfeld et al. is used to calculate the complexity of an intensity matrix. Because no single variation is most efficient for all beams tested, we suggest implementing multiple variations of our algorithm.
During the large-scale sequencing analysis of a human fetal brain cDNA library, we isolated two cDNA clones encoding two novel proteins, which show 52% and 72% identity to the cyclophilin isoform 10 of C. elegans, respectively. Sequence analysis revealed these two cDNA clones are two different splicing variants of a novel cyclophilin-like gene (PPIL3). The PPIL3 gene was identified on a completely sequenced BAC (GenBank accession AC005037) from chromosome 2q33 between STS markers stSG2762 (proximal) and SHGC-3074 (distal), oriented toward the telomere. The PPIL3 gene consisted of eight exons spanning more than 18 kb of genomic DNA. RT-PCR analysis indicated that PPIL3 was ubiquitously expressed in adult human tissues.
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To investigate the role of iron and active oxygen species (AOS) in asbestos-induced fibrosis, we loaded increasing amounts of Fe(II)/Fe(III) onto the surface of amosite asbestos fibers and then applied the fibers to rat tracheal explants. Explants were harvested after 7 d in air organ culture. Asbestos by itself doubled procollagen gene expression, and a further increase was seen with increasing iron loading; actual collagen content measured as hydroxyproline was increased in a similar pattern. Iron loading also increased gene expression of platelet-derived growth factor (PDGF)-A and transforming growth factor (TGF)-beta(1). Neither asbestos alone nor iron-loaded asbestos affected gene expression of PDGF-B, tumor necrosis factor-alpha, or TGF-alpha. The AOS scavenger tetramethylthiourea or treatment of fibers with the iron chelator deferoxamine prevented asbestos-induced increases in procollagen, PDGF-A, and TGF-beta gene expression, whereas glutathione had no effect. The proteasome inhibitor MG-132 abolished asbestos-induced increases in procollagen gene expression but did not affect increases in PDGF-A or TGF-beta(1) expression, whereas the extracellular signal-regulated protein kinase (ERK) inhibitor PD98059 had exactly the opposite effect. We conclude that surface iron as well as the iron-catalyzed generation of AOS play a role in asbestos-induced matrix (procollagen) production and that this process is driven in part through oxidant-induced nuclear factor kappa B activation. Surface iron and AOS also play a role in PDGF-A and TGF-beta gene expression, but through an ERK-dependent mechanism.
Prostate cancer (CaP) forms osteoblastic skeletal metastases with an underlying osteoclastic component. However, the importance of osteoclastogenesis in the development of CaP skeletal lesions is unknown. In the present study, we demonstrate that CaP cells directly induce osteoclastogenesis from osteoclast precursors in the absence of underlying stroma in vitro. CaP cells produced a soluble form of receptor activator of NF-kappaB ligand (RANKL), which accounted for the CaP-mediated osteoclastogenesis. To evaluate for the importance of osteoclastogenesis on CaP tumor development in vivo, CaP cells were injected both intratibially and subcutaneously in the same mice, followed by administration of the decoy receptor for RANKL, osteoprotegerin (OPG). OPG completely prevented the establishment of mixed osteolytic/osteoblastic tibial tumors, as were observed in vehicle-treated animals, but it had no effect on subcutaneous tumor growth. Consistent with the role of osteoclasts in tumor development, osteoclast numbers were elevated at the bone/tumor interface in the vehicle-treated mice compared with the normal values in the OPG-treated mice. Furthermore, OPG had no effect on CaP cell viability, proliferation, or basal apoptotic rate in vitro. These results emphasize the important role that osteoclast activity plays in the establishment of CaP skeletal metastases, including those with an osteoblastic component.
OBJECTIVE: To obtain more insight into information of signal transduction of EGF-receptor-mediated pathway response to the stimulation of hepatic stimulator substance (HSS). METHODS: HSS was extracted from weanling rat liver and partially purified. Bioactivity of HSS was confirmed with its ability to proliferate hepatoma cell in vitro. Meanwhile, a rat recombinant HSS vector was constructed and expressed in BL-21 E. Coli. Mitogen-activated protein kinase (MAPK) activation marked by phosphorylation at Thr202/Tyr204 was determined by Western blot. RESULTS: The molecular weight of the biochemically purified HSS was found identically to that of the recombined HSS as expressed in the prokaryotic cells. After the treatment of HSS, cellular MAPK phosphorylation was initiated obviously at 15 min and maintained to 30 min. In comparison with EGF, MAPK phosphorylation as stimulated by HSS appeared less intensive and later time-kinetics as well. The HSS induction on cellular MAPK phosphorylation was gradually inhibited by PD98059, a specific inhibitor of MAPK kinase (MEK). A complete blockade was seen at 100 micromol/L of PD98059. CONCLUSIONS: The involvement of HSS on MAPK activation implies that this liver-specific growth factor might take part in, either individually or as combined with other growth factors, the regulation of TPK signaling cascade during hepatocyte proliferation.
In order to study the toxicokinetics of terephthalic acid(TPA) in rats, and provide scientific basis for its biological exposed index (BEI), the concentrations of urine TPA in rats after single oral administration in dose of 100 mg/kg BW were determined by high pressure liquid chromatography. The toxicokinetic parameters were computed by using 3P97 program. The results showed that the first-order kinetics and two-compartment model were noted on the elimination of TPA. The main toxicokinetic parameters were as follows: Ka = 0.51/h, T1/2ka = 0.488 h, T1/2 alpha = 2.446 h, Tpeak = 2.160 h, Ku = 0.143/h, T1/2 beta = 31.551 h, Xu(max) = 10.00 mg. The excretion rates of TPA in urine were about 50%, 52% and 53% in 0-24 h, 0-48 h and 0-72 h respectively after administration. TPA is well absorbed when given orally and rapidly eliminated via urine. Urine TPA at the end of work shift should be considered as a biomarker of exposure for the occupational workers.
Expression of neutral endopeptidase (NEP) 24.11 is diminished in metastatic, androgen-independent prostate cancers (PCs; C. N. Papandreou et al., NAT: MED:, 4: 50--57, 1998). To determine the effects on androgen-independent PC cells of overexpressing cell-surface NEP, an inducible tetracycline-regulatory gene expression system was used to stably introduce and express the NEP gene in androgen-independent TSU-Pr1 cells generating WT-5 cells, which expressed high levels of enzymatically active NEP protein when cultured in the absence of tetracycline. TN12 cells, which contain the identical vectors without the NEP gene and do not express NEP, were used as control. Expression of NEP in WT-5 cells after removal of tetracycline from the media resulted in a >80% inhibition in cell proliferation over a 1-week period (P < 0.005) compared with control cells. Tumor formation occurred in the prostate glands of orthotopically injected athymic mice killed at 30 days in 4 of 5 mice that were given injections of 2 x 10(6) WT-5 cells and were fed doxycycline (NEP suppressed), and in all mice that were given injections of TN12 cells and were fed with or without doxycycline. In contrast, only 1 of 5 mouse prostates developed a tumor in mice that were given injections of WT-5 cells and that did not receive doxycycline. Analysis of the mechanisms of NEP-induced growth suppression revealed that NEP expression in WT-5 cells induced a 4-fold increase in the number of PC cells undergoing apoptosis, and increased the expression of p21 tumor suppressor gene protein and the level of unphosphorylated retinoblastoma protein as determined by Western blot. Flow cytometric analysis show that induced NEP expression in WT-5 cells resulted in a G(1) cell cycle arrest. These data show that NEP can inhibit PC cell growth and tumorigenicity and suggest that NEP has potential as therapy for androgen-independent PC.
Silk fibroin peptides could be obtained from soluble silk fibroin by enzymatic hydrolysis. Its hydrolyzates produced with Alcalase showed significant inhibitory activity against the angiotensin I-converting enzyme (ACE). One inhibitory peptide from the hydrolyzate at a degree of hydrolysis of 20% (sample A20) was purified and identified. Sample A20 was first isolated by size exclusion chromatography(SEC), eluted with 0.01 mol/L hydrochloric acid solution on a Sephadex G-15 column (1.6 cm i.d. x 100 cm). The peak of No. 5 on the SEC chromatography was further purified by reversed-phase HPLC (mu Bondapak C18 P/N 84176 column, 7.8 mm i.d. x 300 mm), eluted with a linear gradient elution with acetonitrile from 0% to 15% at temperature (30 +/- 2) degrees C. Then the pure peptide with ACE inhibitory activity was obtained, the amino acid sequence of which was identified as Gly-Tyr by mass spectrometry.
Hypersil BDS C18 and Zorbax SB C18, suitable to separate simultaneously seven kinds of catechins and caffeine, were screened out from seven brands of reversed-phase columns. Mobile phase was a solution of methanol-water-acetic acid (or trifluoro acetic acid). Seven kinds of catechins in tea samples from six places in China and three green tea polyphenol(GTP) samples from different producers were separated and determined in 30 min by isocratic and gradient elutions. The effects of mobile phase components and temperature of column on retention parameters of catechins and caffeine are reviewed. Chromatographic conditions and pretreatment methods of samples were optimized. Gallocatechin gallate(GCG) and (-)-catechin gallate(CG) were identified by electrospray ionization mass spectrometry(ESI-MS) and prepared by high performance liquid chromatography for quantitative analysis. The other catechins, (-)-epigallocatechin (EGC), (+)-catechin (D-C), (-)-epicatechin(EC), (-)-epigallocatechin gallate(EGCG), (-)-epicatechin gallate(ECG) were identified with standards.