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Biomedical subjects

S Oishi

Publications and source records attributed to S Oishi.

At least 19 recordsLinked to original sources
PubMed2001

Conformational study of a highly specific CXCR4 inhibitor, T140, disclosing the close proximity of its intrinsic pharmacophores associated with strong anti-HIV activity.

We report the solution structure of T140, a truncated polyphemusin peptide analogue that efficiently inhibits infection of target cells by T-cell line-tropic strains of HIV-1 through its specific binding to a chemokine receptor, CXCR4. Nuclear magnetic resonance analysis and molecular dynamic calculations revealed that T140 has a rigidly structured conformation constituted by an antiparallel beta-sheet and a type II' beta-turn. A protuberance is formed on one side of the beta-sheet by the side-chain functional groups of the three amino acid residues (L-3-(2-naphthyl)alanine, Tyr5 and Arg14), each of which is indispensable for strong anti-HIV activity. These findings provide a rationale to dissect the structural basis for the ability of this compound to block the interaction between CXCR4 and envelope glycoproteins from T-tropic strains of HIV-1.

Amino Acid Sequence↗
PubMed2001

Unusual early bile excretion from the liver in patients with fulminant hepatic failure as detected by Tc-99m-PMT hepatobiliary scintigraphy; comparison with Tc-99m-GSA scintigraphy.

In two females (58 and 14 years old) with fulminant hepatic failure, Tc-99m-PMT hepatobiliary scintigraphy was used to evaluate intrahepatic bile stagnation, and Tc-99m-GSA scintigraphy to evaluate hepatic functional reserve. In both patients, Tc-99m-PMT hepatobiliary scintigraphy showed unusual early bile excretion into the extrahepatic bile duct and small intestine within the first 30 min of imaging. These findings contradicted typical findings of intrahepatic bile stagnation of fulminant hepatic failure. The receptor index and blood clearance index determined from dynamic acquisition data on Tc-99m-GSA scintigraphy suggested a markedly decreased hepatic functional reserve. These findings were compatible with fulminant hepatic failure. A discrepancy was observed between the findings of hepatobiliary scintigraphy and those of Tc-99m-GSA scintigraphy. The pathological state of early bile excretion from the liver into the bile duct should be considered in fulminant hepatic failure.

Adolescent↗
PubMed2001

Testicular toxicity of dietary 2,2-bis(4-hydroxyphenyl)propane (bisphenol A) in F344 rats.

Male F344/DuCrj (Fischer) rats were given bisphenol A (BPA) in the diet at levels of 0 (control), 0.25, 0.50 and 1.00%, equivalent to 0, 235, 466 and 950 mg/kg per day, respectively, for 44 days. Body weight gains were depressed dose-dependently in BPA-treated rats, and those of 0.50 and 1.00% groups were significant. Testis and epididymis weights were not significantly decreased. Both absolute and relative weights of dorsolateral prostate and preputial glands were reduced in a dose-related fashion. Absolute weights of seminal vesicles and hypophysis were also decreased. Histopathologically, seminiferous tubule degeneration and loss of elongated spermatids were observed, the severity being related to BPA dose. The disorganization, distortion and degeneration of late spermatids, and the atrophy of seminiferous tubules were found even in the 0.25% BPA group. Serum testosterone concentrations were not decreased in BPA-treated groups. These results indicate that BPA even at a level of 0.25% (235 mg/kg per day) is clearly toxic to male reproductive organs.

Administration, Oral↗
PubMed2001

A new polymorph of barium chloroanilate trihydrate.

Single crystals of a new polymorph of the title compound, barium(II) 3,6-dichloro-2,5-dihydroxy-1,4-benzoquinone trihydrate, Ba2+.C6Cl2O4(2-).3H2O, have been grown in sodium metasilicate gel. Each Ba2+ cation is coordinated by eight O atoms. The Ba2+ cations are bridged by an O atom of a ligand around the centre of symmetry at Wyckoff position 4a and by the O atom of a water molecule around the centre of symmetry at Wyckoff position 4b, forming a sheet parallel to the (100) plane. Loose contacts are found around one of the water molecules, as observed in the Cmca form.

Journal Article↗
PubMed2001

End effects of rated life quality: the James Dean Effect.

In three studies, we explored how the ending of a life influences the perceived desirability of that life. We consistently observed that participants neglected duration in judging the global quality of life. Across all the studies, the end of life was weighted heavily, producing ratings that contradict a simple hedonic calculus in which years of pleasure and pain are summed. Respondents rated a wonderful life that ended abruptly as better than one with additional mildly pleasant years (the "James Dean Effect"). Similarly, a terrible life with additional moderately bad years was rated as more desirable than one ending abruptly without those unpleasant years (the "Alexander Solzhenitsyn Effect"). Finally, embedding moderately intense years in the middle of life did not produce effects as strong as adding those years to the end of life, suggesting that a life's ending is weighted especially heavily in judging quality of life.

Adult↗
PubMed2000

Pharmacophore identification of a specific CXCR4 inhibitor, T140, leads to development of effective anti-HIV agents with very high selectivity indexes.

A polyphemusin peptide analogue, T22 ([Tyr(5,12), Lys7]-polyphemusin II), and its shortened potent analogues, T134 (des-[Cys(8,13), Tyr(9,12)]-[D-Lys10, Pro11, L-citrulline16]-T22 without C-terminal amide) and T140 [[L-3-(2-naphthyl)alanine3]-T134], strongly inhibit the T-cell line-tropic (T-tropic) HIV-1 infection through their specific binding to a chemokine receptor, CXCR4. T22 is an extremely basic peptide possessing five Arg and three Lys residues in the molecule. In our previous study, we found that there is an apparent correlation in the T22-related peptides between the number of total positive charges and anti-HIV activity or cytotoxicity. Here, we have conducted the conventional Ala-scanning study in order to define the anti-HIV activity pharmacophore of T140 (the strongest analogue among our compounds) and identified four indispensable amino acid residues (Arg2, Nal3, Tyr5, and Arg14). Based on this result, a series of L-citrulline (Cit)-substituted analogues of T140 with decreased net positive charges have been synthesized and evaluated in terms of anti-HIV activity and cytotoxicity. As a result, novel effective inhibitors, TC14003 and TC14005, possessing higher selectivity indexes (SIs, 50% cytotoxic concentration/50% effective concentration) than that of T140 have been developed.

Amino Acid Sequence↗
PubMed2000

Direct comparison of electron transfer properties of two distinct semisynthetic triads with non-protein based triad: unambiguous experimental evidences on protein matrix effects.

In order to understand the roles of protein matrix in electron transfer processes (ET) within biological systems, a heme-based donor (Zn-heme: ZnPP)-sensitizer (Ru2+(bpy)3)-acceptor (cyclic viologen: BXV4+) triad 1 was used as a probe molecule. Two semi-synthetic systems, Cyt-b562(1) and Mb(1), in which the triad is incorporated into cytochrome b562 (Cyt-b562) or into myoglobin (Mb), were constructed by cofactor reconstitution. These two semi-synthetic proteins were compared with the triad itself (i.e., without the protein matrix) using absorption spectroscopy, steady state emission and excitation studies, laser flash photolysis experiments, and molecular modeling. Photoexcitation of the ZnPP moiety of Cyt-b562(1) or Mb(1) leads to a direct ET from the triplet state of ZnPP state (3ZnPP) to BXV4+ to generate a final charge-separated (CS) state, Cyt-b562(Zn+)-Ru2+-BXV3+* or Mb(Zn+)-Ru2+-BXV3+*. On the other hand, direct ET from the excited ZnPP moiety to the BXV4+ moiety is also involved in 1 in the absence of the protein matrix, but the excited state of ZnPP involved is not 3ZnPP, but the singlet excited state (1ZnPP) in this pathway. When the Ru2+(bpy)3 moiety of Cyt-b562(1) or Mb(1) is excited, a stepwise ET relay occurs with the ion-pair, Cyt-b562(Zn)-Ru3+-BXV3+* or Mb(Zn)-Ru3*-BXV3+*, as an intermediate, leading to the same final CS state as that generated in the direct ET pathway. The lifetimes of the corresponding final CS states were determined to be 300 ns for 1 in the absence of the protein matrix, 600-900 ns for Cyt-b562(1) and 1.1-18 micros for Mb(1), the values of which are greatly affected by the protein matrix. Molecular modeling study of the three systems consistently explained the differences of their photophysical behavior.

Cytochrome b Group↗
PubMed2000

Cultural variation in the use of current life satisfaction to predict the future.

Three studies examined cultural and situational influences on the tendency for people to use their current life satisfaction to predict future life events. On the basis of the self-enhancement literature, it was predicted that either writing about a positive personal experience or reading about another's negative experience would lead European Americans to focus their attention on internal attributes and thus would lead them to use their current life satisfaction in predicting the future. Conversely, on the basis of the self-criticism literature, it was predicted that these same conditions would lead Asian Americans to focus their attention on external factors and, therefore, would decrease their likelihood of using their current life satisfaction to predict the future. Studies 1 and 2 supported these hypotheses. Study 3 showed that these patterns could be obtained by subliminally priming concepts associated with individualism and collectivism.

Adolescent↗
PubMed2000

Abnormal pulmonary accumulation of indium-111 chloride in pneumocystis carinii pneumonia as detected by bone marrow scintigraphy.

PURPOSE: Unusual pulmonary uptake of In-111 chloride in a patient with Pneumocystis carinii pneumonia and autoimmune hepatitis is described. METHOD: In-111 chloride bone marrow scintigraphy was performed to evaluate the bone marrow activity associated with pancytopenia in a 56-year-old woman with autoimmune hepatitis. RESULTS: An In-111 chloride bone marrow scan showed increased pulmonary uptake predominantly in both upper lung fields. P. carinii pneumonia was seen to be developing as an immunocompromised complication after treatment for autoimmune hepatitis. CONCLUSION: When In-111 chloride bone marrow scintigraphy shows increased uptake in the lungs of immunocompromised patients, a combined opportunistic inflammatory disease such as P. carinii pneumonia should be considered in the diagnosis.

Bone Marrow↗
PubMed2000

Disposition of orally administered 2,2-Bis(4-hydroxyphenyl)propane (Bisphenol A) in pregnant rats and the placental transfer to fetuses.

We studied the disposition of bisphenol A (BPA) in pregnant female F344/DuCrj(Fischer) rats and its placental transfer to fetuses after a single oral administration of 1 g/kg BPA dissolved in propylene glycol. BPA in maternal blood, liver, and kidney reached maximal concentrations (14.7, 171, and 36 microg/g) 20 min after the administration and gradually decreased. The levels were 2-5% of the maximum 6 hr after the administration. The maximal concentration of BPA in fetuses (9 microg/g) was also attained 20 min after the administration. BPA levels then gradually reduced in a similar manner to maternal blood. These results suggest that the absorption and distribution of BPA in maternal organs and fetuses are extremely rapid and that the placenta does not act as a barrier to BPA.

Absorption↗
PubMed2000

Effects of cadmium administration on the endogenous metal balance in rats.

The concentrations of cadmium and other metal ions in selected organs, urine, and blood of female rats were measured after exposure to cadmium chloride through their diet or by oral or intravenous administration. The hematological and urinary variations were followed for 4 wk. Body weight gain and the weights of livers and kidneys from all treated groups were not significantly different from the controls. No gross morphological changes were observed in any of the tissues studied at necropsy. The accumulation of cadmium occurred in the liver and kidney. The zinc levels in these organs were elevated relative to controls, in all treated groups regardless of dose and exposure route. Copper was elevated in the liver, kidney, bone, and blood of animals subject to intravenous administration of cadmium. Hepatic iron was decreased in the dietary and orally treated groups, but was not affected in the intravenous study group. The level of magnesium in kidney was increased for all exposure routes, but that of liver was increased only in the intravenously injected groups. The changes in the concentrations of sodium, potassium, calcium, and phosphorus did not follow a specific pattern and varied from organ to organ, depending on the exposure route. The discussion includes a relationship between tissue injury and the alteration of tissue essential element concentrations.

Animals↗
PubMed2000

The psychological trade-offs of goal investment.

The primary goal of this research was to investigate the possibility that being very invested in goals has psychological trade-offs. Self-report methods were used in a concurrent study with college students (Study 1) and a longitudinal study with elementary school children (Study 2). The results of both studies provided support for the hypothesis that high goal investment has psychological trade-offs. Such investment was associated with positive emotions as well as with worrying, both concurrently and longitudinally. In addition, evidence for mediational mechanisms was provided: Perceptions of accomplishment accounted for the relation between goal investment and positive emotions; the link between goal investment and worrying was mediated by predictions that failure would be upsetting. The implications of these findings for distinguishing between depressive and anxiety symptoms are discussed.

Adolescent↗
PubMed1999

Plasmodium falciparum domain mediating adhesion to chondroitin sulfate A: a receptor for human placental infection.

Malaria during the first pregnancy causes a high rate of fetal and neonatal death. The decreasing susceptibility during subsequent pregnancies correlates with acquisition of antibodies that block binding of infected red cells to chondroitin sulfate A (CSA), a receptor for parasites in the placenta. Here we identify a domain within a particular Plasmodium falciparum erythrocyte membrane protein 1 that binds CSA. We cloned a var gene expressed in CSA-binding parasitized red blood cells (PRBCs). The gene had eight receptor-like domains, each of which was expressed on the surface of Chinese hamster ovary cells and was tested for CSA binding. CSA linked to biotin used as a probe demonstrated that two Duffy-binding-like (DBL) domains (DBL3 and DBL7) bound CSA. DBL7, but not DBL3, also bound chondroitin sulfate C (CSC) linked to biotin, a negatively charged sugar that does not support PRBC adhesion. Furthermore, CSA, but not CSC, blocked the interaction with DBL3; both CSA and CSC blocked binding to DBL7. Thus, only the DBL3 domain displays the same binding specificity as PRBCs. Because protective antibodies present after pregnancy block binding to CSA of parasites from different parts of the world, DBL-3, although variant, may induce cross-reactive immunity that will protect pregnant women and their fetuses.

Animals↗
PubMed1998

Identification of cytochrome P450 isozymes involved in metabolism of the alpha1-adrenoceptor blocker tamsulosin in human liver microsomes.

1. The in vitro human liver metabolism of the alpha1-adrenoceptor blocker tamsulosin was investigated. When 14C-tamsulosin was incubated with human liver microsomes, it was converted to five known urinary metabolites and at least three unknown metabolites. Of the former group, the predominant metabolite was the O-deethylated metabolite (M-1), followed by the o-ethoxyphenoxy acetic acid (AM-1) and the m-hydroxylated metabolite (M-3). 2. There was a good linear relationship between AM-1 formation and testosterone 6beta-hydroxylase activity in microsomes from each of 10 individual donors. The rate of M-1 formation also correlated with the same activity, albeit the correlation curve did not pass through the origin. By contrast, the rates of M-3 and the O-demethylated metabolite (M-4) formation correlated with dextromethorphan O-demethylase activity. 3. Ketoconazole strongly inhibited AM-1 formation and reduced that of M-1 by c. 60%. Immunoinhibition studies using anti-rat antibodies supported these results. The formation of M-3 and M-4 was inhibited by quinidine and sparteine. 4. It is concluded that formation of tamsulosin metabolites, AM-1 and M-1, is catalysed by CYP3A4 whereas that of M-3 and M-4 is catalysed by CYP2D6. However, minor contributions from other CYPs cannot be excluded.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1997

Chronic toxicity studies of piperonyl butoxide in CD-1 mice: induction of hepatocellular carcinoma.

Male and female CD-1 mice (51-104 mice/group) were administered piperonyl butoxide (alpha-[2-(2-butoxyethoxy)ethoxy-4,5-methylenedioxy-2-propyltol uene) in the diet at levels of 0 (control), 0.6 and 1.2% for 52 weeks (1 year). Hepatocellular carcinomas were induced in treated groups in a dose-dependent manner. The incidences of hepatocellular carcinoma were 11.3 and 52.0% in male mice given 0.6 and 1.2% piperonyl butoxide, and 41.2% in female mice given 1.2%. Piperonyl butoxide is thus a hepatocarcinogen to mice as it is known to be to rats.

Animals↗
PubMed1996

Pennyroyal toxicity: measurement of toxic metabolite levels in two cases and review of the literature.

BACKGROUND: Pennyroyal is a widely available herb that has long been used as an abortifacient despite its potentially lethal hepatotoxic effects. However, quantitative data for pennyroyal constituents and their metabolites in humans have not been previously reported. OBJECTIVES: To quantify pennyroyal metabolites in human overdose, to correlate these findings with clinical variables, and to place these findings in the context of previously reported cases of pennyroyal toxicity. DESIGN: Clinical case series of pennyroyal ingestions; quantification of pennyroyal metabolites by gas chromatography and mass spectrometry; qualitative detection of protein-bound adducts of the metabolites of pennyroyal constituents in human liver by Western blot assay; and review of the literature based on a search of MEDLINE, Index Medicus, and the reference citations of all available publications. RESULTS: We report four cases of pennyroyal ingestion. One patient died, one received N-acetylcysteine, and two ingested minimally toxic amounts of pennyroyal and were not treated with N-acetylcysteine. In the fatal case, postmortem examination of a serum sample, which had been obtained 72 hours after the acute ingestion, identified 18 ng of pulegone per mL and 1 ng of menthofuran per mL. In a serum sample from the patient treated with N-acetylcysteine, which had been obtained 10 hours after ingestion, the menthofuran level was 40 ng/mL. Review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patients who had been exposed to at least 10 mL of pennyroyal oil. CONCLUSION: Pennyroyal continues to be an herbal toxin of public health importance. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potential role of N-acetylcysteine. Better understanding of the toxicity of pennyroyal may also lead to stricter control of and more restricted access to the herb.

Acetylcysteine↗