Biomedical subjects

Y Takeda

Publications and source records attributed to Y Takeda.

At least 361 records · Page 20Linked to original sources

PubMed1998

Significance of water solubility in the gastrointestinal absorption of trans-bis(n-valerato)(1R,2R-cyclohexanediamine)(oxalato)platinum(IV), an orally active antitumor platinum complex, and its analogs.

Trans-bis(n-valerato)(1R,2R-cyclohexanediamine)(oxalato++ +)platinum(IV) (C5-OHP) is an orally active platinum complex we prepared. The gastrointestinal absorption of C5-OHP was examined in rats and compared with those of C5-OHP analogs which have a general formula of trans-bis(n-OCOCnH2n+1)(1R,2R-cyclohexanediamine)(oxalato )platinum(IV) as well as C5-OHP. The complexes did not show significant differences in pharmacokinetic behavior after i.v. injection. Plasma platinum level after a single oral administration at a dose was higher for a complex with higher water solubility. The intestinal absorption rate measured by an in situ recirculating perfusion technique was higher for a complex with higher lipophilicity. These results indicate that the water solubility is a more dominant factor than the lipophilicity in the gastrointestinal absorption of the complexes. Then, the effects of surfactants and alpha-cyclodextrin (alpha-CD) on the solubility of C5-OHP was studied. Among the agents tested, alpha-CD showed the highest effect in increasing the solubility. Administration of C5-OHP together with alpha-CD gave approximately three times higher plasma platinum levels than administration of C5-OHP alone. Water solubility was found to be a dominant factor in the gastrointestinal absorption of C5-OHP and its analogs.

Animals↗

PubMed1998

I-123 uptake in nonfunctional struma ovarii.

A case of nonfunctional struma ovarii preoperatively diagnosed by scintigraphy of the pelvis using I-123 NaI is reported. US, CT, and MRI revealed a multilobulated mass composed of cystic and solid components. CT showed cystic components with slightly high density and MRI showed various signal intensities on T1- and T2-weighted images. I-123-scintigraphy of the pelvis showed uptake in the pelvic mass. Microscopic examination revealed the histologic appearance of thyroid tissue accompanied by follicular adenoma. I-123 scintigraphy of the pelvis was useful for reaching the correct preoperative diagnosis in this patient with nonfunctional struma ovarii.

Adenoma↗

PubMed1998

Differentiation of benign from malignant nodules by accumulation of Tc-99m pertechnetate using TI-201 delayed scans.

Thyroid carcinoma usually is characterized by a nonfunctioning or "cold" nodule depicted on the Tc-99m scan. Twelve patients with functioning "hot" thyroid nodules underwent thyroidectomy (nine hemithyroidectomies, two nodulectomies, and one subtotal thyroidectomy). Histologic examination revealed that five patients (42%) had malignant nodules (papillary carcinoma in two and follicular carcinoma in three). Of the seven patients with benign nodules, five had follicular adenoma and two had adenomatous hyperplasia. TI-201 scanning (early and delayed) was performed at the same time as Tc-99m scanning. Only one of the seven benign nodules showed accumulation on the delayed TI-201 scan, whereas all five malignant nodules showed accumulation. The delayed TI-201 scan is useful for the differentiation of benign from malignant nodules that show accumulation of Tc-99m pertechnetate.

Diagnosis, Differential↗

PubMed1998

Pleomorphic adenoma of the minor salivary gland with pseudoepitheliomatous hyperplasia of the overlying oral mucosa: report of two cases.

Two cases of intra-oral pleomorphic adenoma with marked pseudoepitheliomatous hyperplasia of the overlying oral mucosa are reported. Incisional biopsy specimens, taken a few weeks before surgical excision of the tumor, showed no squamous cell element. Surgically excised specimens revealed pseudoepitheliomatous hyperplasia with hyperortho- and para-keratinization, which extended from overlying oral squamous epithelium, where an incisional biopsy was performed into the deep tumor area. Approximately half of the tumor area in case 1 and one-third in case 2 were occupied by hyperplastic squamous epithelium of the oral mucosa. Although the induction mechanism of such prominent pseudoepitheliomatous hyperplasia of the overlying oral mucosa occupying more than one-third of the tumor area could not be understood, it is thought that surgical injury and/or focal anesthesia during the incisional biopsy played an important role. To the best of our knowledge, these two cases represent the first reported association between benign salivary gland tumor and marked pseudoepitheliomatous hyperplasia of the overlying oral mucosa.

Adenoma, Pleomorphic↗

PubMed1998

Elevated fetal fibronectin in midtrimester amniotic fluid is involved with the onset of preeclampsia.

OBJECTIVE: To examine early midtrimester amniotic fluid for its significance in pregnancy outcomes, especially with connection to the pathogenesis of preeclampsia. METHODS: A prospective, nested, case-control study was conducted. Fetal fibronectin in early midtrimester (16-20 weeks gestation) amniotic fluid was measured by EIA method. Results were compared by their pregnancy outcomes. RESULTS: Amniotic fluid levels of fetal fibronectin were significantly higher in the group subsequently developing severe preeclampsia (106.8 +/- 13.2 micrograms/ml, mean +/- SD, n = 12) compared with matched controls (66.7 +/- 7.1 micrograms/ml, n = 12) (p < 0.05). CONCLUSION: High levels of fetal fibronectin were found in the amniotic fluid of women subsequently developing severe preeclampsia before any symptom appear. Involvement of extracellular injury or cellular hyperactivity in the midtrimester placental site with the onset of preeclampsia is suggested.

Adult↗

PubMed1998

Development and evaluation of a multiplex PCR assay for rapid detection of toxigenic Vibrio cholerae O1 and O139.

A multiplex polymerase chain reaction assay was developed for concurrent detection of rfb sequences specific for the O1 and the O139 serogroups of Vibrio cholerae and for ctxA specific sequences. The multiplex PCR assay was found to be highly specific and sensitive and was capable of detecting 65 cfu and 200 cfu per assay of V. cholerae O1 and O139, respectively. Evaluation of the multiplex PCR assay using 121 stool samples from patients admitted to the Infectious Diseases Hospital, Calcutta, showed the assay to be 100% sensitive and 95.2% specific when the culture method was taken as the standard. In addition to the 38 PCR positive stool samples, an additional four samples which were negative by culture method but positive by PCR assay belonged to the O139 serogroup. All the 38 stool samples positive for either O1 or O139 serogroup by PCR assay were also positive for the ctxA amplicon indicating that the O1 and O139 V. cholerae strains have the genetic potential of producing cholera toxin.

Bacterial Proteins↗

PubMed1998

Elevated IL-6 in midtrimester amniotic fluid is involved with the onset of preeclampsia.

PROBLEM: The primary defect of placental development in preeclampsia is speculated to occur at midtrimester gestation. Abnormal feto-maternal immune reactions have been considered as factors in such defective placentation. METHOD OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and gestations measured for cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL-1 beta, IL-6, and IL-8). The effect of each cytokine on thrombomodulin levels was tested in cultured trophoblast cells. RESULTS: Among the measured cytokines, IL-6 and IL-8 were significantly elevated in the midtrimester amniotic fluid of the future preeclamptic group. Trophoblasts stimulated with TNF-alpha plus IL-6 had significantly decreased levels of cellular thrombomodulin compared to those without cytokine addition. CONCLUSIONS: Elevated cytokines in midtrimester amniotic fluid suggest an abnormal fetomaternal immune response occurring before the clinical manifestation of preeclampsia. Cytokine-induced suppression of thrombomodulin in trophoblasts may be directly involved in the pathogenesis of preeclampsia.

Amniocentesis↗

PubMed1998

[Evaluation of commercial kits for a rapid detection of Escherichia coli O157 in stool].

To introduce rapid detection of E. coli O157 in the stool without culturing, nine different commercial kits for detection of E. coli O157 were compared. VIP, Reveal, Path Stik, Quix, Now EH and EZ coli were found to detect E. coli O157 greater than 10(6) CFU/ml. TECRA and Novapath could detect more than 10(5) CFU/ml. VIDAS reacted positive with more than 10(4) CFU/ml. TECRA, Novapath, Quix could detect 1:4, 1:4, 1:9 dilution of stool specimen spiked with E. coli O157 respectively, but others could not detect with 1:9 dilution of stool specimen. When stool specimens spiked with E. coli O157 were diluted ten times, centrifuged slightly and supernatants were tested, Path Stik, Quix and EZ coli could detect 10(7) CFU/ml. TECRA and Novapath could detect 10(6) CFU/ml, whereas VIDAS could detect 10(6) CFU/ml. Quix is therefore one of the most suitable kit for detection of E. coli O157 in the stool at the bedside, although some non-specific reactions were observed. Path Stik is also convenient kit at the bedside. VIDAS, although it requires special equipment, is the most sensitive kit for detection of E. coli O157 and is suitable for detection of low levels of E. coli O157 in the clinical laboratory.

Escherichia coli O157↗

PubMed1998

Sequencing and characterization of the xyl operon of a gram-positive bacterium, Tetragenococcus halophila.

The xyl operon of a gram-positive bacterium, Tetragenococcus halophila (previously called Pediococcus halophilus), was cloned and sequenced. The DNA was about 7.7 kb long and contained genes for a ribose binding protein and part of a ribose transporter, xylR (a putative regulatory gene), and the xyl operon, along with its regulatory region and transcription termination signal, in this order. The DNA was AT rich, the GC content being 35.8%, consistent with the GC content of this gram-positive bacterium. The xyl operon consisted of three genes, xylA, encoding a xylose isomerase, xylB, encoding a xylulose kinase, and xylE, encoding a xylose transporter, with predicted molecular weights of 49,400, 56,400, and 51,600, respectively. The deduced amino acid sequences of the XylR, XylA, XylB, and XylE proteins were similar to those of the corresponding proteins in other gram-positive and -negative bacteria, the similarities being 37 to 64%. Each polypeptide of XylB and XylE was expressed functionally in Escherichia coli. XylE transported D-xylose in a sodium ion-dependent manner, suggesting that it is the first described xylose/Na+ symporter. The XylR protein contained a consensus sequence for binding catabolites of glucose, such as glucose-6-phosphate, which has been discovered in glucose and fructose kinases in bacteria. Correspondingly, the regulatory region of this operon contained a putative binding site of XylR with a palindromic structure. Furthermore, it contained a consensus sequence, CRE (catabolite-responsive element), for binding CcpA (catabolite control protein A). We speculate that the transcriptional regulation of this operon resembles the regulation of catabolite-repressible operons such as the amy, lev, xyl, and gnt operons in various gram-positive bacteria. We discuss the significance of the regulation of gene expression of this operon in T. halophila.

Amino Acid Sequence↗

PubMed1998

Mutational analysis of superantigen activity responsible for the induction of skin erythema by streptococcal pyrogenic exotoxin C.

Streptococcal pyrogenic exotoxin C (SPEC), when injected intradermally, induces erythema in unsensitized rabbits. In the present study, we examined whether this erythema induction is due to the T-cell stimulatory activity of SPEC as a superantigen. Analysis by using single-residue mutant SPECs indicated that mutant SPECs Y15I, A16E, and Y17I, in which tyrosine 15, alanine 16, and tyrosine 17 were replaced with isoleucine, glutamic acid, and isoleucine, respectively, exhibited significantly reduced mitogenic activity for Vbeta2(+) human T cells in vitro, and Y15I showed as much as a 1, 000-fold reduction. Y15I mutant SPEC, however, retained the ability to bind to major histocompatibility complex class II antigen and to form a homodimer, implying that residue 15 is critically important for the interaction of SPEC with T-cell antigen receptor beta chains. When injected intradermally into normal rabbits, wild-type SPEC induced a characteristic erythema after 3 h in a dose-dependent fashion, which was associated with polymorphonuclear and mononuclear cell infiltration. This erythema formation was found to be severely suppressed by systemic pretreatment with cyclosporin A, suggesting the involvement of host T cells. Y15I mutant SPEC exhibited nearly 1, 000-fold less erythema induction in vivo than wild-type SPEC. Altogether, the present results strongly suggest that erythema induction in rabbits by SPEC is attributable mostly to its T-cell stimulatory activity as a superantigen.

Amino Acid Sequence↗

PubMed1998

Identification and characterization of a newly isolated shiga toxin 2-converting phage from shiga toxin-producing Escherichia coli.

Shiga toxins 1 (Stx1) and 2 (Stx2) are encoded by toxin-converting bacteriophages of Stx-producing Escherichia coli (STEC), and so far two Stx1- and one Stx2-converting phages have been isolated from two STEC strains (A. D. O'Brien, J. W. Newlands, S. F. Miller, R. K. Holmes, H. W. Smith, and S. B. Formal, Science 226:694-696, 1984). In this study, we isolated two Stx2-converting phages, designated Stx2Phi-I and Stx2Phi-II, from two clinical strains of STEC associated with the outbreaks in Japan in 1996 and found that Stx2Phi-I resembled 933W, the previously reported Stx2-converting phage, in its infective properties for E. coli K-12 strain C600 while Stx2Phi-II was distinct from them. The sizes of the plaques of Stx2Phi-I and Stx2Phi-II in C600 were different; the former was larger than the latter. The restriction maps of Stx2Phi-I and Stx2Phi-II were not identical; rather, Stx2Phi-II DNA was approximately 3 kb larger than Stx2Phi-I DNA. Furthermore, Stx2Phi-I and Stx2Phi-II showed different phage immunity, with Stx2Phi-I and 933W belonging to the same group. Infection of C600 by Stx2Phi-I or 933W was affected by environmental osmolarity differently from that by Stx2Phi-II. When C600 was grown under conditions of high osmolarity, the infectivity of Stx2Phi-I and 933W was greatly decreased compared with that of Stx2Phi-II. Examination of the plating efficiency of the three phages for the defined mutations in C600 revealed that the efficiency of Stx2Phi-I and 933W for the fadL mutant decreased to less than 10(-7) compared with that for C600 whereas the efficiency of Stx2Phi-II decreased to 0.1% of that for C600. In contrast, while the plating efficiency of Stx2Phi-II for the lamB mutant decreased to a low level (0.05% of that for C600), the efficiencies of Stx2Phi-I and 933W were not changed. This was confirmed by the phage neutralization experiments with isolated outer membrane fractions from C600, fadL mutant, or lamB mutant or the purified His6-tagged FadL and LamB proteins. Based on the data, we concluded that FadL acts as the receptor for Stx2Phi-I and Stx2Phi-II whereas LamB acts as the receptor only for Stx2Phi-II.

Animals↗

PubMed1998

Molecular analysis of non-O1, non-O139 Vibrio cholerae associated with an unusual upsurge in the incidence of cholera-like disease in Calcutta, India.

There was an inexplicable upsurge in the incidence of non-O1, non-O139 Vibrio cholerae among hospitalized patients admitted to the Infectious Diseases Hospital, Calcutta, India, between February and March 1996. Of the 18 strains of V. cholerae isolated during this period, 15 belonged to the non-O1, non-O139 serogroups (4 belonged to O144, 3 belonged to O11, 1 each belonged to O6, O8, O12, O19, O39, and O58, and 2 strains could not be typed), 2 belonged to the O139 serogroup, and 1 belonged to the O1 serogroup. Cell-free culture supernatants of 13 representative non-O1, non-O139 V. cholerae strains evoked a distinct cytotoxic effect on CHO and HeLa cells, and the strains examined produced the nonmembrane-damaging cytotoxin. By several PCR assays, it was determined that none of the non-O1, non-O139 strains were positive for the ctxA, zot, ace, and tcpA genes and for the genes representing the heat-labile toxin, heat-stable toxin, and verotoxin of Escherichia coli and the various variants of these genes. Studies on the clonality of non-O1, non-O139 V. cholerae strains by restriction fragment length polymorphism (RFLP) analysis of rRNA genes and of other genes (hlyA, hlyU, hlx, toxR, and attRS1) and by pulsed-field gel electrophoresis (PFGE) collectively indicate that the upsurge which occurred in February and March 1996 was caused by strains belonging to different clones. Overall, there was an excellent correlation between the results of ribotyping, RFLP analysis of various genes, and PFGE, with strains belonging to a particular serogroup showing nearly identical restriction patterns and PFGE profiles. It is clear from this study that some serogroups of V. cholerae can cause diarrhea by a mechanism quite different from that of toxigenic V. cholerae O1 and O139, and we have proposed the nomenclature of enteropathogenic V. cholerae to include these serogroups.

Bacterial Typing Techniques↗

PubMed1998

Molecular epidemiology of reemergent Vibrio cholerae O139 Bengal in India.

We report the prevalence of the O139 serogroup in Calcutta, India, after its reemergence in August 1996 and the spread of the reemerged clone to other parts of the country by using previously established molecular markers. Phenotypically, the reemerged Vibrio cholerae O139 displayed a difference compared to those that appeared in late 1992 and 1993 in that the current O139 strains are sensitive to co-trimoxazole. Ribotyping with the enzyme BglI produced two rRNA restriction patterns in the O139 strains isolated after August 1996, and these patterns were identical to those exhibited by strains of O139 isolated in 1992. Three clones of V. cholerae O139 are currently prevailing in the country, with strains exhibiting three bands after HindIII digestion and hybridization with a ctxA probe being dominant. The reemergence of V. cholerae O139 in Calcutta after a 32-month quiescent period reestablishes the O139 serogroup as an entity which is likely to play a crucial role in the temporal antigenic variations among the serogroups of V. cholerae causing cholera.

Bacterial Typing Techniques↗

PubMed1998

Aldosterone overproduction and CYP11B2 mRNA overexpression in vessels of spontaneously hypertensive rats.

Aldosterone is synthesized in extra-adrenal tissues such as blood vessels and brain. Damage to blood vessels could play a crucial role in perpetuating hypertension. In this study, we determined both aldosterone production and aldosterone synthase gene-CYP11B2 mRNA expression in vessels of spontaneously hypertensive rats (SHR). The results showed that aldosterone was overproduced in the vasculature of SHR, by means of ex vivo mesenteric artery perfusion, HPLC, and RIA, and that CYP11B2 mRNA expression was upregulated in aortas of SHR, confirmed by RT-PCR and Southern blot.

Aldosterone↗

PubMed1998

Renal 11beta-hydroxysteroid dehydrogenase in genetically salt-sensitive hypertensive rats.

-Renal 11beta-hydroxysteroid dehydrogenase II (11beta-HSDII) converts glucocorticoids into inactive metabolites and plays an important role in controlling blood pressure and sodium retention. To examine whether this enzyme may be involved in the pathophysiology of salt-sensitive hypertension, we determined 11beta-HSDII activity and mRNA levels in the blood vessel and kidney of Dahl Iwai salt-sensitive (DS) rats and Dahl Iwai salt-resistant (DR) rats. Urinary free corticosterone:free 11-dehydrocorticosterone ratio was measured to estimate renal 11beta-HSD activity. Vascular 11beta-HSDII activity was expressed as percent conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone in homogenized mesenteric arteries. 11beta-HSDII mRNA was estimated with the use of competitive polymerase chain reaction (PCR). Renal 11beta-HSDII activity and mRNA levels were significantly decreased in 8- and 12-week-old high salt DS rats compared with DR, Sprague-Dawley (SD), or low salt DS rats of the same age. Decreased 11beta-HSDII activity and mRNA levels in mesenteric arteries were observed in 8- and 12-week-old high salt DS rats. Urinary excretion of 11beta-HSDII inhibitory factors was measured by inhibition of enzyme activity in microsomes from human kidney. The urinary inhibitors were significantly increased in 8- and 12-week-old high salt DS rats compared with DR, SD, or low salt DS rats of the same age. There were no significant differences in 11beta-HSDII activity and mRNA levels in mesenteric arteries and kidney or in urinary inhibitors between 4-week-old DS, DR, and SD rats. These results indicate that 11beta-HSDII may play a role in salt sensitivity and development of hypertension in the DS rat.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1998

Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors.

A novel series of phenoxyacetic acid derivatives was synthesized based on considerations of the three-dimensional structural similarity of YM022 and RP72540. The gastrin/cholecystokinin (CCK)-B and CCK-A receptor antagonist activities of these compounds were evaluated by investigation of their affinities for human gastrin/CCK-B receptors and human CCK-A receptors, respectively. It was found that N-methyl-N-phenyl-2-[2-[N-(N-methyl-N-phenyl-carbamoylmethyl)-N-[2 -[3-(3- methylphenyl)ureido]acetyl]amino]phenoxy]acetamide (20k, DZ-3514) exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A receptors.

Acetamides↗

PubMed1998

Synthesis of phenoxyacetic acid derivatives as highly potent antagonists of gastrin/cholecystokinin-B receptors. II.

A series of phenoxyacetanilide derivatives was synthesized and their antagonist activities for human gastrin/cholecystokinin (CCK)-B and CCK-A receptors were evaluated. Among the compounds synthesized, 2-[3-[3-[N-[2-(N-methyl-N-phenylcarbamoylmethoxy)phenyl]-N-(N-meth yl-N- phenylcarbamoylmethyl)carbamoylmethyl]-ureido]phenyl]acetic acid (20i, DA-3934) exhibited high affinity for gastrin/CCK-B receptors and high selectivity over CCK-A receptors. DA-3934 and its methyl ester derivative inhibited pentagastrin-induced gastric acid secretion in rats in a dose-dependent manner.

Acetates↗

PubMed1998

High-dose immunoglobulin G therapy for fulminant myocarditis.

The cardiac function of an adult patient with fulminant myocarditis requiring a mechanical circulatory support was improved, along with the suppressed release of inflammatory mediators, after intravenous infusion with high-dose immunoglobulin. This therapy may have immunomodulatory effects and serve as a potential adjunctive therapy for patients with fulminant myocarditis.

Adjuvants, Immunologic↗