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1.
Hum Comput Interact ; 36(2): 150-201, 2021.
Article in English | MEDLINE | ID: mdl-33867652

ABSTRACT

Digital experiences capture an increasingly large part of life, making them a preferred, if not required, method to describe and theorize about human behavior. Digital media also shape behavior by enabling people to switch between different content easily, and create unique threads of experiences that pass quickly through numerous information categories. Current methods of recording digital experiences provide only partial reconstructions of digital lives that weave - often within seconds - among multiple applications, locations, functions and media. We describe an end-to-end system for capturing and analyzing the "screenome" of life in media, i.e., the record of individual experiences represented as a sequence of screens that people view and interact with over time. The system includes software that collects screenshots, extracts text and images, and allows searching of a screenshot database. We discuss how the system can be used to elaborate current theories about psychological processing of technology, and suggest new theoretical questions that are enabled by multiple time scale analyses. Capabilities of the system are highlighted with eight research examples that analyze screens from adults who have generated data within the system. We end with a discussion of future uses, limitations, theory and privacy.

2.
AJNR Am J Neuroradiol ; 39(5): 864-868, 2018 05.
Article in English | MEDLINE | ID: mdl-29519788

ABSTRACT

BACKGROUND AND PURPOSE: During stent-assisted coiling of ICA aneurysms, stent tips are sometimes unintentionally embedded into ICA branches. Stent tips can be visualized because they have radiopaque markers. Concerns regarding stent tip misplacement include risks of artery perforation and occlusion. The aim of this study was to evaluate the long-term outcomes of ICA branches with embedded stent tips. MATERIALS AND METHODS: ICA branches with embedded stent tips were identified among 35 patients with unruptured ICA aneurysms treated with stent-assisted coiling between November 2003 and November 2014. Patient clinical and angiographic outcomes associated with the embedded stent tip were analyzed. RESULTS: Most of the 35 studied aneurysms were paraclinoid ICA aneurysms (n = 30). The most commonly involved ICA branch was the posterior communicating artery (26 patients, 74.3%), followed by the anterior choroidal artery (8 patients, 22.9%) and ophthalmic artery (1 patient, 2.9%). During the follow-up period (38.6 Ā± 17.9 months), no new neurologic deficits developed. Neither hemorrhagic nor thromboembolic events occurred. Angiography was performed during the final follow-up evaluation at a mean of 32.7 Ā± 18.0 months, and all ICA branches with embedded stent tips showed patent blood flow without severe luminal narrowing. CONCLUSIONS: In our experience, placement of a stent tip into ICA branches during stent-assisted coiling was not associated with any major adverse events.


Subject(s)
Carotid Artery, Internal/pathology , Embolization, Therapeutic/adverse effects , Endovascular Procedures/adverse effects , Intracranial Aneurysm/therapy , Stents/adverse effects , Adult , Aged , Embolization, Therapeutic/instrumentation , Endovascular Procedures/instrumentation , Female , Humans , Male , Middle Aged , Treatment Outcome
3.
Cell Death Differ ; 13(1): 84-95, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16003391

ABSTRACT

Calmodulin (CaM) influences many cellular processes by interacting with various proteins. Here, we isolated AtBAG6, an Arabidopsis CaM-binding protein that contains a central BCL-2-associated athanogene (BAG) domain. In yeast and plants, overexpression of AtBAG6 induced cell death phenotypes consistent with programmed cell death (PCD). Recombinant AtBAG6 had higher affinity for CaM in the absence of free Ca2 + than in its presence. An IQ motif (IQXXXRGXXXR, where X denotes any amino-acid) was required for Ca2 +-independent CaM complex formation and single amino-acid changes within this motif abrogated both AtBAG6-activated CaM-binding and cell death in yeast and plants. A 134-amino-acid stretch, encompassing both the IQ motif and BAG domain, was sufficient to induce cell death. Agents generating oxygen radicals, which are known to be involved in plant PCD, specifically induced the AtBAG6 transcript. Collectively, these results suggest that AtBAG6 is a stress-upregulated CaM-binding protein involved in plant PCD.


Subject(s)
Apoptosis/physiology , Arabidopsis Proteins/metabolism , Calmodulin-Binding Proteins/metabolism , Amino Acid Motifs , Amino Acid Sequence , Arabidopsis/cytology , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Base Sequence , Binding Sites/genetics , Calmodulin-Binding Proteins/genetics , Cloning, Molecular , DNA, Plant/genetics , Genes, Plant , HSC70 Heat-Shock Proteins/genetics , HSC70 Heat-Shock Proteins/metabolism , Molecular Sequence Data , Mutagenesis, Site-Directed , Protein Structure, Tertiary , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Saccharomyces cerevisiae/cytology , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Sequence Deletion , Sequence Homology, Amino Acid , Transformation, Genetic , Two-Hybrid System Techniques
4.
Poult Sci ; 85(6): 1107-13, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16776483

ABSTRACT

The effect of irradiation on thiobarbituric acid reactive substances (TBARS) and volatile compounds in raw and cooked nonirradiated and irradiated chicken breast meat infused with green tea and grape seed extracts was investigated. Chicken breast meat was vacuum infused with green tea extract (3,000 ppm), grape seed extract (3,000 ppm), or their combination (at a total of 6,000 ppm), irradiated with an electron beam, and stored at 5 degrees C for 12 d. The targeted irradiation dosage was 3.0 kGy and the average absorbed dosage was 3.12 kGy. Values of TBARS and volatile compound contents of raw and cooked chicken meat were determined during the 12-d storage period. Thiobarbituric acid reactive substances values ranged from 15.5 to 71.4 mg of malondialdehyde/kg for nonirradiated raw chicken and 17.3 to 80.1 mg of malondialdehyde/kg for irradiated raw chicken. Values for cooked chicken ranged from 31.4 to 386.2 and 38.4 to 504.1 mg of malondialdehyde/kg for nonirradiated and irradiated chicken, respectively. Irradiation increased TBARS and hexanal values of controls and meat infused with plant extracts. Hexanal had the highest intensity of volatiles followed by pentanal and other volatiles. Cooking the samples significantly (P < 0.05) increased the amounts of TBARS and volatiles. Addition of plant extracts decreased the amount of TBARS as well as hexanal and pentanal values. Although irradiation increases lipid oxidation, infusion of chicken meat with plant extracts could reduce lipid oxidation caused by irradiation.


Subject(s)
Chickens , Food Irradiation , Meat/analysis , Plant Extracts/administration & dosage , Thiobarbituric Acid Reactive Substances/analysis , Aldehydes/analysis , Animals , Camellia sinensis/chemistry , Food Irradiation/adverse effects , Hot Temperature , Lipid Peroxidation/drug effects , Seeds/chemistry , Vitis/chemistry , Volatilization
5.
Cancer Res ; 56(6): 1279-82, 1996 Mar 15.
Article in English | MEDLINE | ID: mdl-8640814

ABSTRACT

Helicobacter pylori causes type B gastritis. It shows strong association with the development of gastric carcinoma. A plausible hypothesis for the missing link between H. pylori infection and gastric carcinogenesis involves oxygen free radical-induced DNA damage. To test this hypothesis, we compared the amount of 9-hydroxydeoxyguanosine, a marker for oxygen free radical-induced DNA damage, in the DNA of human gastric mucosa with and without H. pylori infection. Gastric antral biopsies were taken from pediatric patients and volunteers to select H. pylori-positive and H. pylori-negative specimens. The 8-hydroxydeoxyguanosine content of the gastric mucosal DNA was measured after H. pylori-positive and H. pylori-negative volunteers were identified. The increased level of oxidative DNA damage suggests the mechanistic link between H. pylori infection and gastric carcinoma.


Subject(s)
DNA Damage , DNA/chemistry , Deoxyguanosine/analogs & derivatives , Gastric Mucosa/chemistry , Gastritis/genetics , Helicobacter Infections/complications , Helicobacter pylori , Reactive Oxygen Species/toxicity , 8-Hydroxy-2'-Deoxyguanosine , Adolescent , Child , Child, Preschool , DNA/drug effects , Deoxyguanosine/analysis , Female , Gastric Mucosa/microbiology , Gastric Mucosa/pathology , Gastritis/microbiology , Gastritis/pathology , Helicobacter Infections/genetics , Helicobacter Infections/pathology , Humans , Infant , Male
6.
Biochim Biophys Acta ; 1433(1-2): 56-67, 1999 Aug 17.
Article in English | MEDLINE | ID: mdl-10446359

ABSTRACT

In plants, multiple calmodulin (CaM) isoforms exist in an organism which vary in their primary structures in as much as 32 residues out of their 148 amino acids. These CaM isoforms show differences in their expression patterns and/or target enzyme activation ability. To further understand the biological significance of CaM isoforms, we examined whether CaM isoforms act on specific regulatory targets. In gel overlay assays on various soybean tissue extracts, surprisingly, two soybean CaM isoforms (SCaM-1 and SCaM-4) did not show significant differences in their target binding protein profiles, although they exhibited minor differences in their relative target binding affinities. In addition, both SCaM isoforms not only effectively bound five known plant CaMBPs, but also showed competitive binding to these proteins. Finally, immunolocalization experiments with the SCaM proteins in sections of various tissues using specific antibodies revealed similar distribution patterns for the SCaM isoforms except for root tissues, which indicates that the SCaM isoforms are concomitantly expressed in most plant tissues. These results suggest that CaM isoforms may compete for binding to CaMBPs in vivo. This competitive nature of CaM isoforms may allow modulation of Ca(2+)/CaM signaling pathways by virtue of relative abundance and differential target activation potency.


Subject(s)
Calcium-Binding Proteins/metabolism , Calmodulin/metabolism , Plants/metabolism , Binding, Competitive , Calcium-Binding Proteins/analysis , Calcium-Binding Proteins/genetics , Membrane Proteins/metabolism , Protein Isoforms/metabolism , Signal Transduction , Glycine max/chemistry , Glycine max/metabolism
7.
Biochim Biophys Acta ; 1382(1): 80-90, 1998 Jan 15.
Article in English | MEDLINE | ID: mdl-9507071

ABSTRACT

Two antifungal peptides (Pn-AMP1 and Pn-AMP2) have been purified to homogeneity from seeds of Pharbitis nil. The amino acid sequences of Pn-AMP1 (41 amino acid0 residues) and Pn-AMP2 (40 amino acid residues) were identical except that Pn-AMP1 has an additional serine residue at the carboxyl-terminus. The molecular masses of Pn-AMP1 and Pn-AMP2 were confirmed as 4299.7 and 4213.2 Da, respectively. Both the Pn-AMPs were highly basic (pI 12.02) and had characteristics of cysteine/glycine rich chitin-binding domain. Pn-AMPs exhibited potent antifungal activity against both chitin-containing and non-chitin-containing fungi in the cell wall. Concentrations required for 50% inhibition of fungal growth were ranged from 3 to 26 micrograms/ml for Pn-AMP1 and from 0.6 to 75 micrograms/ml for Pn-AMP2. The Pn-AMPs penetrated very rapidly into fungal hyphae and localized at septum and hyphal tips of fungi, which caused burst of hyphal tips. Burst of hyphae resulted in disruption of the fungal membrane and leakage of the cytoplasmic materials. To our knowledge, Pn-AMPs are the first hevein-like proteins that show similar fungicidal effects as thionins do.


Subject(s)
Antifungal Agents/chemistry , Antimicrobial Cationic Peptides , Lectins/chemistry , Plant Proteins/chemistry , Seeds/chemistry , Amino Acid Sequence , Animals , Antifungal Agents/isolation & purification , Antifungal Agents/pharmacology , Bacteria/drug effects , Biological Assay , Cell Line , Cell Survival/drug effects , Fungi/drug effects , Fungi/physiology , Fungi/ultrastructure , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Molecular Sequence Data , Molecular Weight , Plant Lectins , Plant Proteins/isolation & purification , Plant Proteins/pharmacology , Sequence Alignment , Sequence Homology, Amino Acid , Serine , Spores, Fungal
8.
Eye (Lond) ; 29(12): 1555-60, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26293140

ABSTRACT

UNLABELLED: Purpose: To evaluate and compare surgical outcomes with respect to refractive errors in strabismus surgery for the treatment of intermittent exotropia (IXT). METHODS: The medical records of patients with IXT who were treated by one surgeon from January 2005 and June 2011 were reviewed. Three hundred and thirty-three IXT patients were included and divided into three groups according to preoperative refractive error: IXT with hyperopia (group I), IXT with emmetropia (group II), and IXT with myopia (group III). The surgical outcomes with respect to sensory and motor criteria were compared among the three groups. RESULTS: The surgical success rates according to motor criteria and sensory and motor criteria combined were higher in groups I (29 patients) and III (124 patients) than in group II (180 patients) at postoperative 3 and 6 months and at the last follow-up. Stereopsis was significantly better in groups II and III than in group I preoperatively (P=0.002 by one-way analysis of variance test); however, the difference was not significant postoperatively. Twenty patients in group I (69.0%) were prescribed undercorrected hyperopic spectacles postoperatively, while only 22 patients in group III (17.7%) were prescribed spectacles with more myopic power than their refractive errors. CONCLUSION: In the surgical treatment of IXT, hyperopia was not an indicator of poor prognosis. Taking into consideration the age effect, follow-up period after IXT surgery, and stereopsis improvement, hyperopic refractive error is rather a good prognostic factor.


Subject(s)
Exotropia/surgery , Hyperopia/diagnosis , Hyperopia/etiology , Oculomotor Muscles/surgery , Ophthalmologic Surgical Procedures/adverse effects , Child , Child, Preschool , Depth Perception/physiology , Eyeglasses , Female , Humans , Hyperopia/therapy , Male , Prognosis , Retrospective Studies , Risk Factors
9.
Minerva Cardioangiol ; 63(6): 495-505, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25283168

ABSTRACT

AIM: The effects of beta-blockers in pediatric and congenital heart disease (CHD) patients suffering from heart failure are controversial. We performed a meta-analysis to determine whether beta-blockers are effective for heart failure in pediatric and CHD patients. METHODS: We searched for clinical trials focusing on clinical on clinical and ventricular functional/dimensional changes after beta-blocker therapy in PubMed (from its inception to August 2013) and bibliographies of identified studies. Studies investigating any of three beta blockers (carvedilol, bisoprolol, and extended release metoprolol succinate) which are known to be effective in adult patients with heart failure were included. RESULTS: Of the 158 screened, 17 (N.=476) fulfilled the study criteria and were analyzed. Beta-blockers were associated with significant improvements in left ventricular (LV) ejection fraction (EF) (12.47%; 95% CI, 10.36 to 14.61), fraction shortening (5.75%; 95% CI, 4.42 to 7.08), LV end-diastolic dimension (-2.91 mm; 95% CI, -5.46 to -0.36), and LV systolic dimension (-4.03 mm; 95% CI, -6.81 to -1.25). No significant change in the pooled mean difference of the right ventricular (RV) EF (3.50%; P=0.08) was observed. However, the RV EF in the untreated group showed a deteriorating trend (-3%), which was different from the trend in the treatment group. There was a significant reduction in the incidence of clinical worsening (odds ratio, 2.15; 95% CI, 1.27 to 3.66). CONCLUSION: Beta-blocker therapy was associated with a significant improvement of echocardiographic parameters in patients with systemic LV failure. However, the use of beta-blockers did not provide significant benefits in terms of improving the EF in patients with RV failure. Nonetheless, beta-blockers may be effective to prevent the clinical deterioration of pediatric and CHD patients with heart failure.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Heart Defects, Congenital/drug therapy , Heart Failure/drug therapy , Age Factors , Bisoprolol/therapeutic use , Carbazoles/therapeutic use , Carvedilol , Child , Heart Defects, Congenital/physiopathology , Heart Failure/physiopathology , Humans , Metoprolol/therapeutic use , Propanolamines/therapeutic use , Ventricular Dysfunction, Left/drug therapy
10.
Trends Biotechnol ; 14(5): 153-8, 1996 May.
Article in English | MEDLINE | ID: mdl-8645449

ABSTRACT

Recent advances in biomedical science in general, and molecular biology in particular, have provided a greater understanding of pathogenesis at the molecular and (sub)cellular level. In turn, this has stimulated the development of macromolecular, mechanism-based therapeutic agents, ranging from recombinant proteins, to oligonucleotides, to genes/gene fragments. The factors essential for the successful development of this new class of therapeutic agents are not necessarily the same as those for the development of conventional small organic molecules. This review mentions several issues relating to the development of macromolecular drugs, and emphasizes the key issue of drug transport and delivery.


Subject(s)
Biotechnology/trends , Drug Delivery Systems/trends , Drug Design , Molecular Weight
11.
Mol Plant Microbe Interact ; 13(4): 470-4, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10755311

ABSTRACT

In order to study molecular interactions that occur between rice and rice blast fungus upon infection, we isolated fungal elicitor-responsive genes from rice (Oryza sativa cv. Milyang 117) suspension-cultured cells treated with fungal elicitor prepared from the rice blast fungus (Magnaporthe grisea) employing a method that combined mRNA differential display and cDNA library screening. Data base searches with the isolated cDNA clones revealed that the OsERG1 and OsERG2 cDNAs share significant similarities with the mammalian Ca2+-dependent lipid binding (C2) domains. The OsCPX1 cDNA is highly homologous to peroxidases. The OsHin1 cDNA exhibits homology to the tobacco hin1 gene, whose expression is induced by avirulent pathogens. The OsLPL1 and OsMEK1 cDNAs share homologies with lysophospholipases and serine/threonine mitogen-activated protein (MAP) kinase kinases, respectively. The OsWRKY1 and OsEREBP1 cDNAs are homologous to transcription factors, such as the WRKY protein family and the AP2/EREBP family, respectively. Transcripts of the OsERG1, OsHin1, and OsMEK1 genes were specifically elevated only in response to the avirulent race KJ301 of the rice blast fungus. Our study yielded a number of elicitor-responsive genes that will not only provide molecular probes, but also contribute to our understanding of host defense mechanisms against the rice blast fungus.


Subject(s)
Magnaporthe/pathogenicity , Oryza/metabolism , Plant Proteins/metabolism , RNA, Plant/metabolism , Signal Transduction/genetics , Blotting, Northern , Cells, Cultured , Oryza/microbiology , Plant Proteins/analysis , RNA, Messenger/analysis , RNA, Plant/analysis , Virulence
12.
FEBS Lett ; 486(2): 103-6, 2000 Dec 08.
Article in English | MEDLINE | ID: mdl-11113447

ABSTRACT

Possible functions that have been proposed for the plant 1Cys-peroxiredoxin, include activity as a dormancy regulator and as an antioxidant. The transcript level of rice 1Cys-peroxiredoxin (R1C-Prx) rapidly decreased after imbibition of rice seeds, but the protein was detected for 15 days after imbibition. To investigate the function of this protein, we generated transgenic tobacco plants constitutively expressing the R1C-Prx gene. The transgenic R1C-Prx plants showed a germination frequency similar to control plants. However, the transgenic lines exhibited higher resistance against oxidative stress, suggesting that antioxidant activity may be its primary function.


Subject(s)
Antioxidants , Oryza/enzymology , Peroxidases/physiology , Animals , Gene Expression , Germination/physiology , Oryza/genetics , Oryza/physiology , Oxidative Stress , Peroxidases/genetics , Peroxiredoxins , Plants, Genetically Modified , Plants, Toxic , Rabbits , Seeds/physiology , Nicotiana
13.
J Thromb Haemost ; 1(2): 363-73, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12871512

ABSTRACT

The peptide LSARLAF (LSA) causes alphaIIbbeta3-dependent platelet activation that results in alpha-granule secretion and aggregation. LSARLAF-induced, alphaIIbbeta3-mediated outside-in signaling causing alpha-granule secretion and platelet aggregation was studied using washed mouse platelets. ADP receptor antagonists, enzyme inhibitors, normal platelets and platelets from mice that lack either Galphaq or thromboxane (Tx) A2 receptors were used for this investigation. The results demonstrate that LSA-induced alphaIIbbeta3-mediated signaling producing aggregation of washed platelets is mediated through the release of ADP and thromboxane, which cause alpha-granule release by mediating their effects though Galphaq and/or Gi depending on the level of LSA used to activate the platelets. Specifically, alphaIIbbeta3 elicited aggregation of washed platelets in response to a low level of LSA requires signaling through the ADP receptor P2Y1 and Galphaq, and the ADP receptor P2Y12 and Gi as well as TxA2 receptors. However, this aggregation is independent of Galphaq and TxA2 signaling in response to high LSA concentrations, but is dependent on ADP signaling through its receptor P2Y12, and therefore presumably Gi, regardless of the level of LSA used to activate the platelets. PKC function is required for ADP secretion and the subsequent signaling through P2Y12 regardless of the level of LSA used to activate the platelets. The end point of the LSA-induced alphaIIbbeta3-mediated signaling characterized in this study is alpha-granule secretion, which provides the fibrinogen required for aggregation of washed platelets.


Subject(s)
Blood Platelets/drug effects , Blood Platelets/physiology , Oligopeptides/pharmacology , Platelet Glycoprotein GPIIb-IIIa Complex/physiology , Adenosine Diphosphate/blood , Animals , Cell Degranulation/drug effects , Cell Degranulation/physiology , Female , GTP-Binding Protein alpha Subunits, Gq-G11 , Heterotrimeric GTP-Binding Proteins/blood , In Vitro Techniques , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Phosphatidylinositol 3-Kinases/blood , Platelet Aggregation/drug effects , Platelet Aggregation/physiology , Protein Kinase C/blood , Receptors, Purinergic P2/blood , Receptors, Thromboxane/blood , Signal Transduction/drug effects
14.
J Med Chem ; 29(8): 1346-50, 1986 Aug.
Article in English | MEDLINE | ID: mdl-3016261

ABSTRACT

A 1,4-benzodiazepine analogue alprazolam (1) undergoes ring-opening hydrolysis under acidic conditions to form a triazolobenzophenone (2). At a neutral pH, 2 rapidly and quantitatively cyclizes back to 1. This facile reversible reaction was utilized in developing water-soluble prodrugs of 1 in which the "solubility anchoring" acyl moieties are formyl, acetyl, succinyl, glycyl, leucyl, and gamma-aminobutyryl groups. These compounds were prepared directly from 2 and corresponding acids through DCC coupling in a 1:1 mixture of H2O and THF. They should be stable in aqueous media at room temperature. Promoieties used should be nontoxic at an intended dose level. In vitro human serum hydrolysis study showed that only glycyl and leucyl amides were able to regenerate 1 within a reasonable period of time. Ex vivo competitive receptor binding assay in mice with [3H]flunitrazepam indicated that leucyl amide prodrug should be able to produce a rapid onset of the intrinsic central nervous system activity of 1 when parenterally administered. For all compounds studied, the final outcome of the biological response appears to be kinetically controlled, rather than by an unfavorable equilibrium, particularly by the first step in which the amide bond is hydrolyzed in vivo.


Subject(s)
Benzodiazepines/administration & dosage , Dosage Forms , Alprazolam , Animals , Benzodiazepines/metabolism , Binding, Competitive , Blood , Brain/metabolism , Female , Flunitrazepam/metabolism , Humans , Hydrolysis , In Vitro Techniques , Male , Mice , Receptors, GABA-A/metabolism , Solubility , Water
15.
J Med Chem ; 20(11): 1525-7, 1977 Nov.
Article in English | MEDLINE | ID: mdl-410931

ABSTRACT

In order to improve the chemical stability of prostaglanding E2 (2), prostaglanding E2 ethylene ketal (1) was prepred by direct ketalization of 2 with ethylene glycol in benzene. To establish a quantitative assessment of 1 as a chemically stable and orally active prodrug of 2, the hydrolysis of 1 to 2 and the subsequent dehydration of 2 to prostaglandin A2 (3) were followed at 25 degrees C and six pH's ranging from 2.0 to 6.5 by means of a high-pressure liquid chromatographic procedure. Kinetic results clearly indicate that 1 should be quantitively hydrolyzed back to the parent drug 2 dehydration of 2 to 3 are in the order of 1 h and 14 days, respectively. The preliminary data on the biological response after oral administration of 1 appeared to indicate the 1 is bioequivalent to 2.


Subject(s)
Prostaglandins E, Synthetic/chemical synthesis , Acetals/chemical synthesis , Animals , Biological Availability , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , Drug Stability , Female , Haplorhini , Hydrolysis , Kinetics , Macaca mulatta , Pregnancy , Prostaglandins E, Synthetic/pharmacology , Uterine Contraction/drug effects
16.
Virus Res ; 23(1-2): 39-53, 1992 Apr.
Article in English | MEDLINE | ID: mdl-1318627

ABSTRACT

A hepatitis C virus (HCV) genome was isolated and sequenced from a single Japanese patient with chronic non-A, non-B hepatitis. The genome (HCV-JT), which was constructed with 23 cDNA clones, consisted of 9436 nucleotides with a long open reading frame which could encode a sequence of 3010 amino acid residues. To study the sequence variation of the HCV genome in an individual, we analyzed another sequence of the HCV genome (HCV-JT') constructed with different cDNA clones derived from the same patient. The nucleotide variation between HCV-JT and -JT' was less than 1%, and was distributed throughout the genome except in the 5' non-coding region, where no variation was observed. The diversity was higher (1.6%) in the putative envelope protein region than in other regions. The nucleotide and deduced amino acid sequences of HCV-JT showed homologies of about 91 and 95%, respectively, with those of other Japanese HCV isolates. The nucleotide diversity was high in the gp 70 region (corresponding to the NS 1 region of flaviviruses) and low in the 5' non-coding and p22 (putative core protein) regions. A similar pattern of distribution of nucleotide changes was observed on comparison of HCV-JT with an American isolate HCV-US, where the homologies in nucleotide and amino acid sequences were about 79 and 85%, respectively. Base transversions contributed about 50% of the total base exchanges between the Japanese and American HCV sequences, but only 20% or less of those among Japanese HCV or among American HCV sequences. Thus, the Japanese and American HCVs are genetically distinguishable, supporting our earlier prediction that these two HCVs could be classified as different subtypes.


Subject(s)
Carrier State/microbiology , Genetic Variation , Genome, Viral , Hepacivirus/genetics , Hepatitis C/genetics , Amino Acid Sequence , Base Sequence , Cloning, Molecular , DNA, Viral/isolation & purification , Hepacivirus/isolation & purification , Hepatitis C/microbiology , Humans , Japan , Molecular Sequence Data , Sequence Homology, Nucleic Acid
17.
Radiother Oncol ; 41(2): 163-7, 1996 Nov.
Article in English | MEDLINE | ID: mdl-9004360

ABSTRACT

BACKGROUND AND PURPOSE: Ginkgo biloba leaf extract (GBE) is known to increase peripheral blood circulation. The hypothesis that GBE may be able to enhance radiosensitivity of tumor by improving tumor blood flow and thus decreasing hypoxic fraction was tested. MATERIALS AND METHODS: Fibrosarcoma (FSaII) growing in C3H mouse leg muscle was used as a tumor model. GBE was given i.p. 1 h before irradiation with or without priming dose given 1 day earlier. Effect on tumor and normal tissue radiation reaction was investigated. RESULTS: Tumor growth delay by radiation was more elongated after two doses (1-day interval) of GBE than after a single dose. Radiation dose for 3-day tumor growth delay was decreased from 12.45 (10.97-13.93) Gy to 6.06 (3.89-8.22) Gy by two doses of GBE [enhancement ratio = 2.06 (1.32-2.79)]. Hypoxic cell fraction was 10.6% (6.3-18.2%) for control, 7.2% (3.8-14.0%) after a single dose (P = 0.18) and 2.7% (1.5-5.0%) after two doses (P < 0.001). Radiation effect on normal tissue, estimated by acute skin reaction and jejunal crypt assay, was not affected by GBE. CONCLUSION: Ginkgo biloba extract enhances radiation effect on tumor without increasing acute normal tissue radiation damage in this model system probably by increasing tumor blood flow and further investigation for this possible radiosensitizer is needed.


Subject(s)
Fibrosarcoma/radiotherapy , Muscle Neoplasms/radiotherapy , Plant Extracts/therapeutic use , Radiation-Sensitizing Agents/therapeutic use , Animals , Cell Hypoxia , Female , Male , Mice , Mice, Inbred C3H , Neoplasm Transplantation , Radiation Dosage
18.
Radiother Oncol ; 56(2): 175-9, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10927136

ABSTRACT

PURPOSES: The objectives of this prospective clinical trial were to determine whether pentoxifylline improves the radiation response and survival in patients with non-small cell lung cancer. MATERIALS AND METHODS: From July 1993 through October 1994, 64 patients with histologically confirmed Stage I, II and III non-small cell lung cancer were randomly divided into pentoxifylline (Pento)+Radiotherapy (RT) group and RT alone group. Out of the 64 patients, only 47 patients who had measurable tumors on chest X-ray views were analyzed and divided into Pento+RT group (n=27) and RT alone group (n=20). Total tumor dose of 65-70 Gy was delivered as conventional fractionated radiation schedules. Pento was given to the patients 3 x 400 mg/day with a daily dose of 1200 mg during RT. RESULTS: Complete response (CR), partial response (PR), and stable in Pento+RT group were three (11%), 13 (48%), and 11 (41%), respectively, as compared with corresponding values of three (15%), 13 (65%), and four (20%) in the RT alone group. The median time to relapse in the Pento+RT group was 11 months which was 2 months longer than for the RT alone group (P>0.05). All the patients in both groups showed lower than or equal to grade 2 dysphagia, odynophagia, pulmonary fibrosis, and pneumonitis. The median survival was 18 months in the Pento+RT group and 7 months in the RT alone group. The 1-year survival rate was 60% in the Pento+RT group and 35% in the RT alone group, the 2-year survival rate was 18% in the Pento+RT group and 12% in the RT alone group. But these differences were not statistically significant (P>0.05). CONCLUSION: We concluded that Pento is a modestly effective radiation response modifier and provide benefit in the treatment of non-small cell lung cancer.


Subject(s)
Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Pentoxifylline/administration & dosage , Radiation-Protective Agents/administration & dosage , Radiotherapy/methods , Aged , Carcinoma, Non-Small-Cell Lung/mortality , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Lung Neoplasms/mortality , Male , Middle Aged , Probability , Prospective Studies , Radiotherapy, Adjuvant , Survival Analysis , Treatment Outcome
19.
Psychopharmacology (Berl) ; 144(3): 272-8, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10435394

ABSTRACT

RATIONALE: CNS-active drugs produce specific electroencephalographic changes and the concentration-effect relationship of antipsychotics may be elucidated by adopting electroencephalography (EEG) as an effect measurement tool. OBJECTIVE: The purpose of the present study was to determine the concentration-effect relationship of risperidone by assessing the EEG effect after oral administrations of single dose risperidone in healthy young males. METHODS: Nine healthy male volunteers received a 1 mg single oral dose of risperidone according to a placebo controlled crossover design. Plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone were measured by radioimmunoassay. Quantitative EEG parameters were obtained for each of four frequency bands through spectral EEG analysis. The difference in the absolute power in the delta frequency band for the F3 lead between risperidone and placebo was used as a drug effect parameter. For pharmacokinetic-pharmacodynamic modeling, the hypothetical effect compartment kinetically linked to plasma by a first-order process was postulated. All curve fittings were done with the non-linear curve-fitting program NONLIN. RESULTS: Our results showed that absolute powers in delta and theta frequency bands were higher for risperidone administration than for placebo at all EEG leads, and the maximum effects were detected at about 3 h after administration of the drug. The hysteresis loop was observed in the plot of plasma concentration of risperidone or sum of risperidone and 9-hydroxyrisperidone (Cp) versus EEG effect for each subject. A linear model adequately described the relationship between the effect compartment concentrations (Ce) and EEG effects, and the two limbs of hysteresis in the Cp-effect plot were collapsed in the Ce-effect plot for risperidone or risperidone plus 9-hydroxyrisperidone. CONCLUSION: The increases of absolute power for delta and theta frequency bands of EEG were induced by single oral administration of risperidone. The linear PK-PD model fit well with the relationship between effect compartment concentrations (Ce) and EEG effects of risperidone.


Subject(s)
Antipsychotic Agents/pharmacokinetics , Electroencephalography/drug effects , Risperidone/pharmacokinetics , Administration, Oral , Adult , Antipsychotic Agents/blood , Antipsychotic Agents/metabolism , Antipsychotic Agents/pharmacology , Dose-Response Relationship, Drug , Humans , Isoxazoles/blood , Isoxazoles/pharmacokinetics , Male , Models, Biological , Paliperidone Palmitate , Pyrimidines/blood , Pyrimidines/pharmacokinetics , Risperidone/blood , Risperidone/metabolism , Risperidone/pharmacology
20.
Surgery ; 122(4): 748-54; discussion 754-6, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9347852

ABSTRACT

BACKGROUND: The unexpected intraoperative finding of a cancerous gallbladder has become particularly problematic, because cancer recurs rapidly after laparoscopic cholecystectomy. It would be desirable to identify the patients of greatest risk for gallbladder cancer before operation. After several elderly patients presenting with acute cholecystitis were found to have gallbladder cancer, we performed the following study. METHODS: Records of patients (60 years of age or older, 1987 to 1995) with an admitting diagnosis of acute cholecystitis and symptoms including right upper quadrant pain, nausea, vomiting, fever, and leukocytosis were reviewed. RESULTS: Eighty patients were included in the study. Carcinoma involving the gallbladder was found in seven patients; six had primary and one had metastatic carcinoma. The 73 patients without cancer underwent cholecystectomy. The differences between the noncancer and cancer patients included age (68 +/- 7 versus 74 +/- 8 years, p < 0.05), total bilirubin (mg/dl, 1.5 +/- 1.5 versus 3.7 +/- 3.4, p < 0.01), alkaline phosphatase (IU/L, 179 +/- 132 versus 369 +/- 226, p < 0.01), and aspartate aminotransferase (IU/L, 77 +/- 93 versus 158 +/- 157, p < 0.05). CONCLUSIONS: Additional work-up and open cholecystectomy should be considered in elderly patients presenting with apparent acute cholecystitis, especially when liver functions are abnormal.


Subject(s)
Cholecystectomy, Laparoscopic , Cholecystitis/complications , Gallbladder Neoplasms/epidemiology , Acute Disease , Aged , Aged, 80 and over , Analysis of Variance , Cholecystectomy , Female , Follow-Up Studies , Gallbladder Neoplasms/mortality , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/surgery , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors
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