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S Oishi

Publications and source records attributed to S Oishi.

At least 37 records · Page 2Linked to original sources

[Subacute cor pulmonale due to microscopic pulmonary tumor embolism].

We report a case of subacute pulmonary hypertension caused by microscopic pulmonary tumor embolism due to the dissemination of gastric cancer cells. The patient, a 61-year-old man with no history of malignant diseases, was admitted to our hospital on October 14 in 1998 because of cough and dyspnea on effort, that had developed since the previous month. On admission, chest radiography including CT scans showed slight cardiomegaly and disseminated reticulonodular shadows predominating in the lower lung fields of both lungs, and arterial blood gas analysis disclosed severe hypoxemia. Lung perfusion scintigraphy revealed multiple irregular defects in both lungs. Echocardiography indicated right ventricular overload, and the pulmonary artery systolic pressure was estimated to be higher than 80 mmHg. Disseminated intravascular coagulation (DIC) developed on the 6th day of hospitalization. Multiple pulmonary embolism with DIC of unknown cause was diagnosed, and the patient was given anticoagulant therapy with heparin. However, he died of respiratory failure on the 7th day of hospitalization. At autopsy, an invasive cancer was found in the stomach, resembling type IIc early gastric cancer. The lumens of the pulmonary arterioles were significantly narrowed by fibrocellular proliferation and thrombi accompanying tumor cell clusters, and some of the microvessels were completely occluded. Disseminated microscopic pulmonary metastasis of malignant tumors should be included in the differential diagnosis of subacute pulmonary hypertension due to multiple pulmonary embolism of unknown cause.

Acute Disease↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Germline mutations of the RET proto-oncogene in eight Japanese patients with multiple endocrine neoplasia type 2A (MEN2A).

Multiple endocrine neoplasia type 2A (MEN2A) is a dominantly inherited cancer syndrome characterized by medullary thyroid carcinoma, pheochromocytoma, and parathyroid hyperplasia. The gene responsible for MEN2A was localized by linkage analysis to chromosome 10q11.2 in 1987, and recently mutations in RET, a proto-oncogene in the candidate region, were discovered in patients with MEN. The majority of mutations found so far in MEN2A patients have been located in nucleotide sequences encoding cysteine residues in the extracellular domain of RET. To characterize MEN2A germline alterations in the Japanese population, we screened DNA from eight unrelated patients for mutations in exons 10 and 11 of the RET proto-oncogene and found mutations in all eight patients, at codons 618, 620, or 634; each of these sites encodes a cysteine residue in the extracellular domain of RET. The mutations were confirmed in other affected individuals in the respective families by digestion of polymerase chain reaction (PCR) products containing the mutated codons with restriction enzymes (Rs alpha I, CfoI, or AluI) for which cleavage sites had been generated by the specific genetic alteration. These PCR-restriction enzyme systems will be useful for genetic diagnosis in members of families carrying these mutations.

Base Sequence↗

Defective blood coagulation is not causative of hepatic haemorrhage induced by microcystin-LR.

Male rats were intraperitoneally administered a lethal dose of microcystin-LR (a toxin of cyanobacteria). Prior to haemorrhage in the liver, blood coagulation and platelet aggregation activities were measured. The number of cellular components, white blood cells, red blood cells and, especially, platelets, decreased 1-1.5 hr after the injection. Plasma kaolin-activated partial thromboplastin time was prolonged and fibrinogen concentration was reduced, but antithrombin III activity and fibrin degradation product concentration were not significantly changed. Platelet aggregation was not affected for up to 0.5-1.0 hr after administration. Sequential analyses of those parameters and hepatotoxic markers indicate that those hematologic changes as well as the hepatic injury occur suddenly after the massive bleeding. These results suggest that microcystin-LR does not directly act on the haemostatic system to cause a disseminated intravascular coagulation-like state. The decrease in blood coagulation activity and platelet particle concentration may be the results of secondary consumptive effects following the hepatic haemorrhage.

Animals↗

Preparation and biological activity of 24-epi-26,26,26,27,27,27-hexafluoro- 1 alpha,25-dihydroxyvitamin D2.

A new fluorinated analog of vitamin D2, 24-epi-26,26,26,27,27,27-hexafluoro- 1 alpha,25-dihydroxyvitamin D2, was efficiently synthesized starting from (R)-4-isopropyl-3-propionyl-2- oxazolidinone with high stereochemical control. In all four physiological test systems, the fluorinate vitamin D2 analog was found to be slightly less active than 1 alpha,25-dihydroxyvitamin D3.

Animals↗

Mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A (Sipple's syndrome).

Genetic linkage analyses have traced the loci for multiple endocrine neoplasia type 2A (MEN 2A) to an interval on chromosome 10q11.2. This region encompasses the RET proto-oncogene, a receptor tyrosine kinase gene expressed in medullary thyroid carcinoma (MTC) and pheochromocytoma. By means of genomic polymerase chain reaction (PCR) amplification and DNA sequencing, we have analysed 19 individuals from two Japanese MEN 2A families for mutations of the RET proto-oncogene in exons 10 and 11. We conducted single-strand conformational polymorphism (SSCP) analysis of the RET proto-oncogene amplified from affected and unaffected family members. The DNA alterations in the RET proto-oncogene caused substitution of a cysteine for a serine at codon 620 in the exon 10 in three patients in one MEN 2A family, 1, and of a cysteine for a tyrosine at codon 634 in the exon 11 in six patients in the MEN 2A family, 2. We could find two asymptomatic MEN2A gene carriers who had no symptoms or signs of MEN 2A by DNA analysis of the RET proto-oncogene. No mutations in these exons were detected in any unaffected normal members of MEN 2A. A DNA alteration in the RET proto-oncogene coding sequence in exon 10 caused a shift on SSCP gels that was characteristic of the disease chromosome in the MEN 2A family, present only in affected members of the family. The DNA change could also be detected by restriction enzyme digestion with RsaI in family 2. Two MEN 2A patients with a cysteine for a tyrosine substitution at codon 634 in the exon 11 had parathyroid hyperplasia. We conclude that the identification of a DNA alteration in the MEN2A gene will permit predictive molecular testing of individuals at risk in these MEN 2A families and the PCR-restriction enzyme system will be useful for genetic diagnosis of members of these MEN 2A families. This information, by providing diagnostic certainty, should improve medical care for affected family members.

Adrenal Gland Neoplasms↗

Coexistence of MEN 2A and papillary thyroid carcinoma and a recurrent pheochromocytoma 23 years after surgery: report of a case and a review of the Japanese literature.

A 59-year-old woman who had undergone bilateral partial adrenalectomy 23 years previously was referred to our hospital because of neck masses and a left adrenal tumor. Fine needle aspiration biopsy of the neck tumor and elevated levels of calcitonin and CEA revealed medullary thyroid carcinoma. Slightly elevated levels of urinary normetanephrine and metanephrine, and results of a clonidine suppression test, CT, magnetic resonance imaging, and 131I-metaiodobenzylguanidine scintigraphy of the abdomen indicated that the left adrenal tumor was a recurrent pheochromocytoma in the residual adrenal gland. After total thyroidectomy, bilateral medullary thyroid carcinomas and papillary thyroid carcinoma were recognized pathologically. Although the coexistence of bilateral pheochromocytoma and medullary thyroid carcinoma is suggestive of multiple endocrine neoplasia (MEN), association of MEN type 2A (MEN 2A) with papillary thyroid carcinoma may have occurred incidentally. A retrospective analysis of 9 cases of pheochromocytoma associated with papillary thyroid carcinoma reported in the Japanese literature demonstrated a male-to-female ratio of 1:8, and an average patient age of 56.2 years. The present case indicates that association between pheochromocytoma and thyroid carcinoma may not always involve medullary thyroid carcinoma.

Adrenal Gland Neoplasms↗