Importance of epidermal growth factor in pathogenesis of fetal growth restriction.
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Amniotic Fluid↗
Biomedical subjects
J He
Publications and source records attributed to J He.
Structure, sequence, and promoter analysis of human disabled-2 gene (DAB2).
Disabled-2 (DAB2 for human and Dab2 for other species) is one of two mammalian orthologues of Drosophila Disabled. DAB2 exhibits properties of a tumor suppressor gene: the expression of DAB2 is eliminated in 85-95% of breast and ovarian tumors; homozygous deletions of the gene have been found in some of these tumors; and reintroduction of DAB2 expression suppresses tumorigenicity of carcinoma cells. To study the mechanisms of loss of expression and to detect possible mutations in tumors, we have investigated the genomic structure of the DAB2 gene. The complete DAB2 gene was identified and sequenced from four overlapping BAC clones found to contain the gene. Complement factor 9 (C9) gene was localized next to the DAB2 gene at the 3'-end of the BAC DNA fragments. The human DAB2 gene is about 35 kb in size and consists of 15 exons and 14 introns, producing an approximately 4-kb message. A spliced variant corresponding to mouse Dab2 p93 and a 3'-end spliced variant were also identified. The translation initiation site resides in the second exon, and the noncoding first exon is separated from the second exon by a 14-kb intron. The 420-bp sequence 5' of exon 1 contains a CpG island (39 CpG sites). This 420-bp putative promoter was found to contain the site for transcription initiation, identified by RNase protection assay, and is sufficient for active transcription in epithelial cells. The information about the gene structure of DAB2 will enable us to analyze possible mutations and the mechanisms of loss of DAB2 expression in tumors.
Adaptor Proteins, Signal Transducing↗
The effect of preoperative transcatheter hepatic arterial chemoembolization on disease-free survival after hepatectomy for hepatocellular carcinoma.
BACKGROUND: Although surgical resection has produced better results than other therapies for local control of hepatocellular carcinoma (HCC), the long term results have not been satisfactory because of a low disease-free survival rate. The effects of preoperative transcatheter arterial chemoembolization (TACE) on improving disease-free survival of HCC after hepatectomy has remained controversial. METHODS: The current study was retrospective survey of 1725 patients who had hepatectomy for HCC between January 1990 and December 1995 and had follow-up data for 1457 cases. The follow-up rate was 84.5%. The significant prognostic factors were analyzed using a Cox proportional hazards survival model, and the disease-free survival was calculated by Kaplan-Meier estimation. Among 1457 cases, 120 patients underwent preoperative TACE and were divided into a one time TACE group, over two times TACE group, an effective group, and ineffective group. RESULTS: Multivariate analyses revealed significant prognostic factors as follows: preoperative TACE number, preoperative TACE effect, preoperative lesion number, intraoperative tumor thrombus, tumor size, tumor gross type, daughter nodules, vascular invasion, and postoperative alpha-fetoprotein value. Kaplan-Meier estimation showed that the 5-year disease-free survival rates of the over two times group, the one time group, and no TACE group were 51.0%, 35.5%, and 21.4%, respectively, and that the mean disease-free survival times of the three groups were 66.4, 22.5 and 12.5 months, respectively. The effective group had a 5-year disease-free survival rate of 56.8%, with a mean time of 90.1 months. CONCLUSIONS: Effective preoperative TACE may be one of the best methods, which can be clinically performed at present, for resectable HCCs including small HCCs for improving disease-free survival after hepatectomy. According to tumor size, range, location, hepatic function, and TACE effect, TACE can be performed 2-4 times preoperatively within 6 months.
Adolescent↗
Selection of initial antihypertensive drug therapy.
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Angiotensin-Converting Enzyme Inhibitors↗
Tetrahydroisoquinoline derivatives containing a benzenesulfonamide moiety as potent, selective human beta3 adrenergic receptor agonists.
Tetrahydroisoquinoline derivatives containing a 4-(hexylureido)benzenesulfonamide were examined as human beta3 adrenergic receptor (AR) agonists. Notably, 4,4-biphenyl derivative 9 was a 6 nM full agonist of the beta3 AR. Naphthyloxy compound 18 (beta3 EC50 = 78 nM) did not activate the beta1 and beta2 ARs at 10 microM, and showed >1000-fold selectivity over binding to the beta1 and beta2 ARs.
Adrenergic beta-3 Receptor Antagonists↗
P18 tumor suppressor gene and progression of oligodendrogliomas to anaplasia.
P18INK4C is a good candidate to be the tumor suppressor gene involved in oligodendrogliomas on 1p32. Loss of heterozygosity on 1p, mutation(s), homozygous deletion(s), and expression of p18 in 30 oligodendroglial tumors were investigated. Loss of heterozygosity on 1p was found in 15 tumors. A p18 mutation was found at an recurrence of an anaplastic oligodendroglioma, but not in the primary, low-grade tumor. No homozygous deletions were found and p18 was expressed in all cases. These results show that p18 alteration is involved in tumor progression in a subset of oligodendrogliomas.
Alleles↗
Rat hippocampal slices need bicarbonate for the recovery of synaptic transmission after anoxia.
The purpose of this study was to see how the nominal removal of bicarbonate (HCO(-)(3)) from the extracellular space of brain tissue influenced recovery of brain tissue from anoxia. Removal of HCO(-)(3) in HEPES-buffered artificial cerebrospinal fluid (aCSF) inhibited almost completely recovery of synaptic transmission in hippocampal slices after anoxia. Altered pH did not contribute to this finding because adjusting intracellular (pH(i)) and extracellular (pH(o)) pH to control levels did not reduce the effect of HCO(-)(3) removal. Our results suggest that HCO(-)(3) levels are important in determining the extent of anoxic or ischemic brain injury.
Animals↗
Heterolytic and homolytic N-H bond dissociation energies of 4-substituted Hantzsch 2,6-dimethyl-1,4-dihydropyridines and the effect of one-electron transfer on the N-H bond activation.
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Chemistry, Organic↗
Seeing the herpesvirus capsid at 8.5 A.
Human herpesviruses are large and structurally complex viruses that cause a variety of diseases. The three-dimensional structure of the herpesvirus capsid has been determined at 8.5 angstrom resolution by electron cryomicroscopy. More than 30 putative alpha helices were identified in the four proteins that make up the 0.2 billion-dalton shell. Some of these helices are located at domains that undergo conformational changes during capsid assembly and DNA packaging. The unique spatial arrangement of the heterotrimer at the local threefold positions accounts for the asymmetric interactions with adjacent capsid components and the unusual co-dependent folding of its subunits.
Capsid↗
Primary role for Gi protein signaling in the regulation of interleukin 12 production and the induction of T helper cell type 1 responses.
We explored the role of Gi protein signaling in the regulation of interleukin (IL)-12 production and T helper cell type 1 (Th1) T cell differentiation. In initial studies, we showed that treatment of normal mice with pertussis toxin (PT), which inhibits Gi protein signaling, enhanced the capacity of splenocytes to produce IL-12 in response to both microbial and nonmicrobial stimuli. In addition, PT treatment increased the production of tumor necrosis factor (TNF)-alpha and IL-10 by stimulated cells. These findings were corroborated by the fact that untreated Gi2alpha(2/-) mice exhibited enhanced production of IL-12 and TNF-alpha by splenocytes, and of IL-12 p40 by purified spleen CD8alpha(+) lymphoid dendritic cells. Finally, we showed that while normal BALB/c mice infected with Leishmania major exhibited a nonhealing phenotype, those treated with PT when infection was initiated exhibited a healing phenotype along with an enhancement of leishmania-specific Th1 responses in draining lymph nodes. Further, healing was prevented by coadministration of anti-IL-12 and PT. These data demonstrate that endogenous Gi protein signaling has a primary role in the regulation of IL-12 production and the induction of Th1 responses in vivo.
Adenosine Diphosphate Ribose↗
Density dependence of the transition temperature in a homogeneous bose-einstein condensate
Transition temperature data obtained as a function of particle density in the 4He-Vycor system are compared with recent theoretical calculations for 3D Bose-condensed systems. In the low density dilute Bose gas regime we find, in agreement with theory, a positive shift in the transition temperature of the form DeltaT/T0 = gamma(na(3))(1/3). At higher densities a maximum is found in the ratio of T(c)/T0 for a value of the interaction parameter, na(3), that is in agreement with path-integral Monte Carlo calculations.
Journal Article↗
Breast carcinoma etiology: current knowledge and new insights into the effects of reproductive and hormonal risk factors in black and white populations.
BACKGROUND: A crossover in breast carcinoma incidence at ages 45-49 years has been observed between black and white women, with blacks experiencing higher incidence at younger ages and lower incidence after age 50 years. Can this phenomenon be partially explained by the differences in the distributions of reproductive risk factors? This article focuses on the effects and distributions of age at first full term pregnancy (FFTP), parity, and oral contraceptive (OC) use in younger versus older and black and white populations. Effects of hormone replacement therapy (HRT) are also summarized. METHODS: A literature review was conducted and information integrated on the effects and distributions of reproductive and hormonal risk factors in black and white populations, the crossover effect of parity, and the Pike model of "breast tissue age." RESULTS: Overall, early age at FFTP and higher parity decreased risk for both races. Distributions of age at FFTP and parity varied widely between the two races. Based on the effects and distributions of age at FFTP and parity, the authors formulated the hypothesis that a crossover in incidence curves between the two races would be expected, rather than be considered an anomaly. Regarding OC use, generally a stronger increase in risk was observed for younger women than for older women. Regarding HRT, a recent meta-analysis observed an increased risk of 1.35 for 5 years of use or more. CONCLUSIONS: To promote public health in diverse populations, and to provide further insight into breast carcinoma etiology, research needs to focus on multicultural differences and similarities in the relation of hormonal risk factors and breast carcinoma.
Black or African American↗
Mass spectrometric study of six cyclic esters
A series of cyclic esters, which are optically active as a consequence of their helical structures, were synthesized to investigate the relationships between their structures and their optical activities. This paper reports the electron impact fragmentation mechanisms of these six cyclic esters. Accurate mass measurements and mass analyzed ion kinetic energy spectrometry confirmed fragmentation patterns. The stability of the fragment ions has a great influence on the fragmentation pathways, but no correlation with the optical activity was found.
Journal Article↗
Asynchronous activation of 10 muscle-specific protein (MSP) genes during zebrafish somitogenesis.
In the present study, 10 zebrafish cDNA clones coding for muscle-specific proteins (MSPs) were characterized and most of them encode fast skeletal muscle isoforms. They are skeletal muscle alpha-actin (acta1), fast skeletal muscle a-tropomyosin (tpma), fast skeletal muscle troponin C (tnnc), fast skeletal muscle troponin T (tnnt), fast skeletal muscle myosin heavy chain (myhz1), fast skeletal muscle myosin light chain 2 (mylz2), fast skeletal muscle myosin light chain 3 (mylz3), muscle creatine kinase (ckm), parvalbumin (pvalb), and desmin (desm). Using these cDNA probes, their expression patterns in developing embryos and adults were compared by Northern blot hybridization and whole-mount in situ hybridization. All of the 10 genes are expressed in both embryos and adult fish, and the expression is highly abundant in skeletal muscle. Among them, acta1, tpma, tnnc, tnnt, myhz1, mylz2, mylz3 and pvalb, are expressed specifically in fast skeletal muscle while ckm and desm are expressed in both fast and slow skeletal muscles. In addition, tpma, ckm, and desm are also expressed in the heart. Ontogenetically, the onset of expression of these MSP genes in zebrafish skeletal muscle varies and the expression occurs rostral-caudally in developing somites. Shortly after the expression of myoD, desm is the first to be activated at approximately 9 hpf, followed by tpma (approximately 10 hpf), tnnc (approximately 12 hpf), acta1 (approximately 12 hpf), ckm (approximately 14 hpf), myhz1 (approximately 14 hpf), mylz2 (approximately 16 hpf), mylz3 (approximately 16.5 hpf), tnnt (approximately 16.5 hpf), and pvalb (approximately 16.5 hpf). At later stages (after 48 hpf), these MSP genes are also expressed in fin buds and head muscles including eye, jaw, and gill muscles. Thus, our experiment demonstrated the order of expression of the 10 MSP genes, which may reflect the sequence of muscle filament assembly. In spite of the asynchrony in activation of these MSP genes, the timing of expression for each individual MSP gene appears to be synchronous to somite development as each somite has an identical timetable to express the set of MSP genes.
Actins↗
Characterization of mesogen-jacketed liquid crystalline polymers by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
For synthetic polymers, a proper sample preparation method is essential for successful characterization by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. In this work, six synthetic mesogen-jacketed liquid crystalline polymers (MJLCPs) with different main-chain, spacer and mesogenic units were investigated by MALDI-TOF mass spectrometry. Several factors that affect the analysis of these polymers were examined. These factors include matrices used, cationization salts used, the concentration of polymers, and the ratio of sample to matrix. After testing different conditions, we found a suitable sample preparation method for these six polymers. The number average molecular weight (M(n)), weight average molecular weight (M(w)) and polydispersity (PD) were calculated using data obtained in the linear mode. The end groups of the polymers were proposed using data obtained in reflectron mode. Copyright 2000 John Wiley & Sons, Ltd.
Journal Article↗
Electron impact fragmentation mechanisms of some cyclic esters with helical structures
The electron impact mass spectra of several cyclic esters with helical structures have been studied. Their fragmentation pathways were proposed and confirmed by mass-analyzed ion kinetic energy (MIKE) and high-resolution data. In general, the dominant fragmentation pathways in the spectra of these compounds originate from a alpha-cleavage with loss of a hydrogen or methyl group. The difference between hydrogen and methyl group loss greatly affects the subsequent fragmentations. Although, due to their helicity, these cyclic esters are optically active no stereo-related fragmentation pathway was observed. Copyright 2000 John Wiley & Sons, Ltd.
Journal Article↗
Enantiomeric separation of an aryloxyphenoxypropanoic acid by CE and LC.
A capillary electrophoresis (CE) and an high performance liquid chromatography (HPLC) chiral separation have been developed for an aryloxyphenoxypropanoic acid, 2-[4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy]propanoic acid, a new antitumor agent. The racemic mixture is analyzed, without derivatization, as the free acids. The CE assay is based on inclusion complexation with hydroxypropyl-beta-cyclodextrin. HPLC separation is achieved with a CSP column with the glycopeptide, teicoplanin, as the chiral selector. Both methods give baseline resolution to the R-and S-isomers. The methods were validated for assay and for optical purity assessment of the R-isomer. For assay, the HPLC method is precise (RSD < 0.6%), accurate (error, 0.5%) and linear (r2 = 0.9998). It is able to precisely (RSD = 0.5%) and accurately (error, 0.9%) detect 0.3-6.0% of one isomer (S) in the other (R). The CE assay is much less precise and accurate than HPLC. It is a good alternative to separate and detect the enantiomers, however.
Antineoplastic Agents↗
Stability-indicating LC assay of and impurity identification in homoharringtonine samples.
Homoharringtonine (HHT) is a potent myelosuppressive agent and has antitumor activity. Recent studies suggest that it inhibits tumor growth by inducing apoptosis. HHT is an ester of the alkaloid cephalotaxine. It is isolated from genus Cephalotaxus. At least ten HHT analogs have been identified from cephalotaxus extracts. High performance liquid chromatography (HPLC) separations of the cephalotaxine alkaloids in plant extracts have been reported, they have not been validated as specific and stability-indicating for HHT. Due to the complexity of the alkaloid extracts, it is conceivable that additional analogs may still be unresolved from HHT. This paper presents an improved and validated HPLC assay for HHT. The assay is stability-indicating, precise (R.S.D. < 1%), linear (r2 = 0.9999), and accurate (error < 1%). The assay reveals three congeners present as impurities in HHT samples. Two are new and have not been previously reported. Identities of the impurities and forced decomposition products, elucidated with their HPLC retention and spectral data, are also presented.
Antineoplastic Agents, Phytogenic↗