Oral FK 506 blood levels are elevated in pig short bowel model: further investigations with co-administration of an intestinal CYP3A4 inhibitor.
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Administration, Oral↗
Biomedical subjects
Y Hayashi
Publications and source records attributed to Y Hayashi.
Dose- and time-response studies of sodium o-phenylphenate urinary bladder carcinogenicity in rats.
Dose- and time-response studies of urinary bladder carcinogenesis due to orally administered sodium o-phenylphenate (OPP-Na) were performed using 5-week-old male Fischer 344 rats given diets containing 0 (control), 2500, 5000, 10,000, 15,000 or 20,000 ppm OPP-Na for 104 weeks and fed basal diets until 112 weeks (experiment 1). In addition, rats received diets containing 20,000 ppm OPP-Na for 0 (control), 12, 24, 52 or 104 weeks and were killed at week 112 (experiment 2). In experiment 1, the transitional cell carcinoma (TCC) was the major tumor type in the urinary bladder, and the dose-response curve was steep with many tumors occurring at the high doses of 15,000 and 20,000 ppm. The virtually safe dose at a risk level of 10(-6) for TCCs and papillomas was estimated to be 144 ppm by the Weibull model, a high value similar to that for sodium saccharin. In experiment 2, a few TCCs developed after 24 weeks of treatment, but the time-response curve was also steep with the majority of lesions occurring after longer exposure periods. Based on the observed steepness in dose- and time-responses, any implied cancer risk of OPP-Na at the low doses of interest to man must be considered to be very small.
Agrochemicals↗
Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder patient with Down syndrome.
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Chromosome Aberrations↗
Regulational effect of ghrelin on growth hormone secretion from perifused rat anterior pituitary cells.
Ghrelin, a novel growth hormone (GH)-releasing peptide, was recently isolated from the rat stomach as an endogenous ligand to growth hormone secretagogue receptor (GHS-R). Ghrelin specifically stimulates the release of GH from the rat anterior pituitary gland, but the regulational effect of ghrelin on GH secretion has not yet been clarified. We used a perifusion system to examine the single effect and combined effects of ghrelin with growth hormone-releasing hormone (GHRH) and somatostatin on GH secretion from rat anterior pituitary cells. The increase in GH concentration due to ghrelin stimulation showed a transitory peak that was almost the same as that previously reported for GHS, but apparently distinct from that of GHRH. Ghrelin (10(-10) M to 10(-8) M) stimulated GH secretion from the rat anterior pituitary cells in a dose-dependent manner. Serial ghrelin stimulation of the dispersed cells at 1-h intervals decreased the GH response, but the response recovered with stimulation at 3-h intervals, indicating that ghrelin strongly desensitized cells. Costimulation with ghrelin and GHRH elicited neither a synergistic nor an additive GH response from the rat pituitary cells. Furthermore, pretreatment to anterior pituitary cells with somatostatin strongly abolished ghrelin- and/or GHRH-stimulated GH secretion. In this study, we demonstrated that ghrelin caused weaker GH secretion than that caused by GHRH, and we also showed that costimulation with GHRH had no additive or synergistic effect on GH secretion, suggesting that ghrelin indirectly affects coordinated GH release from pituitary gland, as found in vivo.
Animals↗
Comparative functional morphology of the masticatory apparatus in the long-snouted crocodiles.
The masticatory muscles and their related structures of the skull were observed in the Indian gavial (Gavialis gangeticus), the false gavial (Tomistoma schlegelii), and the African slender-snouted crocodile (Mecistops cataphractus) to detail some morphological differences in comparison with the other crocodile species, and to compare and elucidate the functional strategy of themasticatory apparatus in these long-snouted species. The Musculus pterygoideus posterior was relatively smaller in the three species compared with many short-snouted crocodiles. It suggests that the masticatory power in fish-eating long-snouted species is not so high as in the short-snouted crocodiles, while the masticatory muscles were morphologically different among the three long-snouted species as follows. The M. pterygoideus posterior of the false gavial was extended in the lateral side of the lower jaw unlike the Indian gavial. The M. pseudotemporalis and the Fenestra supratemporalis were largely developed in the Indian gavial, however we suggest that the other two species possess the weak bundles in this muscle. The false gavial and the African slender-snouted crocodile have the pterygoid bone well-developed extending dorso-ventrally and it is suggested that the M. adductor mandibulae posterior attached to the pterygoid bone may be much larger than the Indian gavial. These data morphologically clarify the masticatory mechanism in the long-snouted crocodiles different from the short-snouted species, and demonstrate that the evolutional strategy to share the functional role in the masticatory muscles have been differently established between the Indian gavial and the other two species. We also obtained the morphological data in the fossil skull of the Machikane crocodile (Toyotamaphymeia machikanense) and concluded from the fossil characters that the considerable developments of the M.pterygoideus posterior and the M.pseudotemporalis in this species had not morphologically been consistent with both the Indian and false gavials.
Alligators and Crocodiles↗
Outcome of hepatoblastoma treated with the JPLT-1 (Japanese Study Group for Pediatric Liver Tumor) Protocol-1: A report from the Japanese Study Group for Pediatric Liver Tumor.
PURPOSE: Hepatoblastoma is the most common malignant liver tumor in childhood. Multicenter studies elucidate the optimal pre- or postoperative chemotherapeutic regimens. This report reviews the results of the Japanese Study Group for Pediatric Liver Tumor Protocol-1 (JPLT-1) and compares its outcomes with published reports of other studies. METHODS: From March 1991 to December 1999, 154 patients with malignant liver tumor including 145 cases of hepatoblastomas were enrolled in the JPLT study. Data from 134 cases were analyzed in this study. JPLT-1 protocol 91A was used for patients with stage I or II hepatoblastoma. The chemotherapy regimen consisted of repeated courses of cisplatin (CDDP), 40 mg/m(2), and tetrahydropyranyl (THP)-Adriamycin, 30 mg/m(2). JPLT-1 protocol 91B was administered to patients with stage IIIA, IIIB, or IV hepatoblastoma. The chemotherapy regimen consisted of repeated courses of CDDP, 80 mg/m(2), and THP-Adriamycin, 30 mg/m(2)/day for 2 days. Courses were repeated every 4 weeks as tolerated. RESULTS: Seven patients died of chemotherapy-related side effects. Six of them died of sepsis caused by leukopenia and 1 case of liver failure. Overall survival rate (3-year/6-year) was 100%/100% for stage I (n = 9), 100%/95.7% for stage II (n = 32), 76.6%/73.8% for stage IIIA (n = 48), 50.3%/50.3% for stage IIIB (n = 25), 64.8%/38.9% for stage IV (n = 20), and 77.8%/73.4% overall. For stage IIIA and B disease, intravenous chemotherapy was better than intraarterial chemotherapy (66.4% v 38.1% for event-free survival and 69.3% v. 57.1% for overall survival). Patients less than 1 year of age had a better prognosis than older patients, but age was not a significant prognostic factor by multivariate analysis. CONCLUSIONS: The overall and event-free survival rates of the JPLT-1 study of hepatoblastoma were comparable with the results of other multicenter studies in Europe and the United States. The event-free survival rate at 3 years for stage IIIB and IV disease was under 50%. New treatment strategies are needed for patients with advanced hepatoblastoma.
Adolescent↗
Comparison of insulinotrophic actions of nateglinide with glibenclamide dissociated from absorption in conscious dogs.
Nateglinide is more rapidly absorbed than glibenclamide. Therefore, the different absorption kinetics of both drugs were eliminated by intraportal administration in conscious fasted dogs. The plasma insulin profiles were compared under similar kinetic changes in plasma drug concentrations. After a priming dose of nateglinide (1 mg/kg. 5 min) or glibenclamide (40 microg/kg. 5 min), plasma drug concentrations reached a peak at 4 minutes (nateglinide, 80 +/- 5 micromol/L, n = 6 and glibenclamide, 263 +/- 60 nmol/L, n = 6) followed by a sustained level at approximately 30% of the peak concentration at 30 minutes. Nateglinide led to a rapid and constant reduction in arterial glucose of approximately 30% basal, while glibenclamide promoted a gradual decrease to approximately 50% basal at 120 minutes. An increase in plasma insulin level by nateglinide of 4 times basal (218 +/- 58 pmol/L v 47 +/- 3 pmol/L, P <.05, n = 6) occurred at 6 to 10 minutes followed by sustained release of 1.4 times basal (67 +/- 15 pmol/L, n = 6). The insulin surge was more than doubled (484 +/- 209 pmol/L, n = 6) under a euglycemic clamp. Insulin release by glibenclamide increased gradually reaching 10-fold basal (449 +/- 166 pmol/L, n = 6) at 60 minutes. This was not enhanced during a euglycemic clamp. Lowering the primed doses of nateglinide resulted in a diminished peak plasma insulin concentration. In contrast, glibenclamide caused only a slower increase, but eventually reaching a similar peak. By increasing the continuous infusion of nateglinide, the sustained insulin release was not altered. Glibenclamide, but not nateglinide, evoked prompt and sustained insulin release in the continuing presence of the other. These results are consistent with the concept that nateglinide produces a quick, but very short-lived, interaction with sulfonylurea (SU)-receptors on plasma membrane by free access of the drug from the cell exterior. In contrast, glibenclamide promotes a slow and longer interaction with the receptor by distribution of the drug into the cell inferior. We conclude, therefore, that not only the different kinetics of gastrointestinal (GI) absorption, but also the inherent difference in the interaction with beta cells is attributed to the different insulin release characteristics between nateglinide and glibenclamide in vivo.
ATP-Binding Cassette Transporters↗
Acquired type 3-like von Willebrand syndrome preceded full-blown systemic lupus erythematosus.
We report a quite rare case of acquired type 3-like von Willebrand syndrome (vWS) that preceded full-blown systemic lupus erythematosus (SLE). A 16-year-old woman with no previous disease history and no family history of hemorrhagic diathesis was referred to our hospital because of recurrent epistaxis and gingival bleeding. She was diagnosed as having atypical type 3 von Willebrand disease because of prolonged bleeding time with normal platelet count and prolonged activated partial thromboplastin time (aPTT), and an almost complete absence of von Willebrand factor (vWF) antigen, ristocetin cofactor activity (vWF:RCo) and ristocetin-induced platelet agglutination (RIPA). Furthermore, electrophoretic analysis of plasma vWF revealed a trace amount of vWF and an absence of the multimeric form of vWF. Infusions of either vasopressin or factor VIII/vWF concentrates improved bleeding symptoms and corrected the aPTT and RIPA. However, she complained of low-grade fever, general fatigue and polyarthralgia 5 months later, and leukocytepenia and hypo-complementemia developed. Anti-double-stranded DNA antibodies and lupus erythematosus cells became positive. These findings were compatible with SLE. Mixing the patient's platelet-poor plasma (PPP) with normal platelet-rich plasma (PRP) (PPP/PRP = 2/1) resulted in a complete inhibition of RIPA, suggesting the presence of vWF inhibitor in her plasma. Treatment with prednisolone (40 mg/day) started and the bleeding tendency gradually improved. One month later, all of the laboratory data including aPTT, bleeding time, RIPA and vWF:RCo became normal. These findings indicate that she has an acquired type 3-like vWS associated with SLE.
Adolescent↗
Congenital arachnoid cyst mimicking meningocele.
The subject of this report is a rare case of a 5-year-old girl who developed an arachnoid cyst with a bony and dural defect in the parietal convexity. She had no history of head trauma or infection. Surgical exploration revealed the bulging lesion to consist of cerebrospinal fluid-containing spongy subcutaneous tissue and to extend into the bony and dural defect. The arachnoid cyst cavity was found beneath the subcutaneous lesion and was not connected to the adjacent subarachnoid space. Histologically, the subcutaneous tissue contained a complex of sinusoidal channels formed by an abundance of migrating arachnoidal cells, thus mimicking meningocele.
Arachnoid Cysts↗
Expression of E-cadherin-catenin complex in human benign schwannomas.
The Ca2+-dependent cell adhesion molecule E-cadherin has been known to express in normal and reactive Schwann cells in rodents, and to play an important role in Schwann cell-Schwann cell adhesion and maintenance of peripheral nervous tissue architecture. However, little is known about expression of E-cadherin in schwannomas. The aim of the present study was to investigate the cellular expression and localization of E-cadherin, and its associated protein, alpha E-, alpha N- and beta-catenins in human schwannomas, which are supposed to derive from Schwann cells. We tested the hypothesis that these proteins might show an altered expression/distribution in schwannoma cells which correlates with their neoplastic behavior, including sparse cell-cell contact, as seen those in meningiomas and various carcinomas. In human schwannomas, however, E-cadherin, alpha E-catenin, and beta-catenin were detected by western blotting and immunohistochemistry, whereas alpha N-catenin was not. Immunoprecipitation using anti-E-cadherin antibody resulted in alpha E-catenin forming a complex with E-cadherin. SSCP analysis revealed no mutations in the transmembrane domain or in intracellular catenin-binding site of E-cadherin. These data suggest that the E-cadherin-alpha E-catenin complex is well preserved in human schwannoma cells, which is compatible with its benign behavior, and these molecules might be used as additional cell markers of Schwann cell-derived tumors.
Adult↗
Postnatal changes in ghrelin mRNA expression and in ghrelin-producing cells in the rat stomach.
Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. Although it is well known that a large amount of ghrelin is produced in the gastrointestinal tract, developmental changes in ghrelin mRNA expression and differentiation of ghrelin-immunopositive (ghrelin-ip) and mRNA-expressing (ghrelin-ex) cells in the stomach have not been elucidated. In this study, we therefore investigated the changes in ghrelin mRNA expression levels and in the numbers of ghrelin-ip and -ex cells in the stomachs of 1- to 8-week-old male and female rats by Northern blot analysis, immunohistochemistry and in situ hybridization. Northern blot analysis showed that the level of weak ghrelin mRNA expression was low in the postnatal period but then increased in a dimorphic pattern, i.e. transient stagnation at 4 weeks in the male rats and at 5 weeks in the female rats. The number of ghrelin-ip and ghrelin-ex cells also increased after birth, and more numerous ghrelin cells were found in female rats than in male rats, and this finding was confirmed by Northern blot analysis. Ghrelin-ip and -ex cells first appeared in the glandular base of the fundic gland and then they were found in the glandular base and the glandular neck at 3 weeks of age, suggesting that the distribution of ghrelin cells is extended from the glandular base to the glandular neck during the postneonatal development period. This is the first report on detailed changes in postneonatal ghrelin expression level and in the number of ghrelin cells in the rat stomach. The sexual dimorphism of ghrelin expression and ghrelin cell differentiation suggest that ghrelin plays an important physiological role in the stomach.
Animals↗
Minimally invasive direct coronary artery bypass for completely obstructed left anterior descending coronary artery.
BACKGROUND: We evaluated the efficacy of minimally invasive direct coronary artery bypass (MIDCAB) using the left internal thoracic artery (LITA) in patients with completely obstructed left anterior descending coronary artery (LAD). METHODS: Ten patients undergoing MIDCAB for LAD stenosis were enrolled in this study. These patients were all men aged 45 to 69 years, and were divided into two groups, one showing complete LAD obstruction (n=5, Group A), and one about 90% stenosis of the LAD (n=5, Group B). RESULTS: The internal size of the LAD at the anastomosis site was significantly smaller in Group A than in Group B, and the time required for graft anastomosis in Group A was significantly longer. Total operation time, intubation time after operation, perioperative bleeding, total blood transfusion, max CK-MB, and hospital stay did not significantly differ between the two groups. Postoperative coronary angiography revealed good graft patency in both groups, however, one Group A patient had graft obstruction. CONCLUSIONS: The MIDCAB procedure appears useful even in our patients with completely obstructed LAD, despite the long anastomosis time. However, the indications for this procedure are limited by any perceived difficulty in harvesting the LITA by indirect vision or in performing the anastomosis based on the size or quality of the LAD. Intensive preoperative angiography evaluation is essential and conversion to a median full-sternotomy is necessary for cases in which we cannot confirm the feasibility of MIDCAB.
Aged↗
Expression of alkaline phosphatase induces rapid and artificial mineralization in specific transformed Escherichia coli.
Matrix vesicles (MV) having high alkaline phosphatase (ALP) activity act as initiators of biological mineralization. Although bacteria have similar membranous structures to MV, ALP mediated mineralization has not been studied in bacterial cells. Escherichia coli was transformed with a bacterial ALP gene in this study. Recombinant E. coli overproducing ALP induced mineralization through hydrolysis of calcium-glycerophosphate (Ca-GP). Fourier transform infrared spectroscopy and electron microscopy combined with electron diffraction revealed newly formed hydroxyapatite mineral deposits. These findings suggest that hydrolysis of Ca-GP through ALP induced high Ca and Pi concentrations within bacterial cells followed by complete bacterial mineralization.
Alkaline Phosphatase↗
Nitrate removal rate in a continuous column denitrification reactor using hydrogen generated by electrolysis with carbon anodes and stainless cathodes.
An autotrophic continuous denitrification process, using hydrogen generated by electrolysis with activated carbon anodes, was experimentally demonstrated to be an effective nitrate removal process. Several fixed bed columns with polypropylene packing and honeycomb shaped activated carbon anodes and stainless rod cathodes were set in a thermostat chamber at 30 degrees C, and potassium nitrate enriched tap water as influent was supplied at various flow rates and electric currents. Although the anode is in the same column where microbial biomass grows, sufficient nitrate removal was observed. For example, almost complete removal of nitrate and nitrite was observed at a hydraulic retention time (HRT) as short as 1.8 h. A model assuming successive denitrification reactions and plug-flow process, nitrate reduction rate = k1 [NO3-] [H2], and nitrite reduction rate = k2 [NO2-] [H2](1.5) was proposed. Calculated results with k1 = 1.3 mmol(-1) h(-1) and k2 = 3.3 mmol(-1.5) x h(-1) agreed well with all the experimental results.
Biofilms↗
Complete response of Sister Mary Joseph Nodule from gastric adenocarcinoma treated with combination chemotherapy of low-dose S-1 and cisplatin.
A case of an unresected, advanced gastric cancer with Sister Mary Joseph nodule was presented. It was treated with new combination chemotherapy of low-dose S-1 and cisplatin producing complete response of periumbilical metastasis. Few treatments are efficacious for umbilical invasion of peritoneal dissemination. A complete response for Sister Mary Joseph nodule from gastric adenocarcinoma has not been ever reported.
Adenocarcinoma↗
Alkynethiolato and alkyneselenolato ruthenium half-sandwich complexes: synthesis, structures, and reactions with (eta(5)-C(5)H(5))(2)Zr.
Alkynethiolato and alkyneselenolato complexes of ruthenium, CpRu(PPh(3))(2)(EC(triple bond)CR) (Cp = eta(5)-C(5)H(5); E = S, R = Ph (1a), SiMe(3) (1b), (t)Bu (1c); E = Se, R = Ph (2a), SiMe(3) (2b)), were synthesized by the reactions of CpRuCl(PPh(3))(2) with corresponding lithium alkynechalcogenolates in THF. An analogous reaction of Cp*RuCl(PEt(3))(2) (Cp* = eta(5)-C(5)Me(5)) with LiSC(triple bond)CPh produced Cp*Ru(PEt(3))(2)(SC(triple bond)CPh) (3). Complexes 1a and 2a were allowed to react in THF with "Cp(2)Zr", generated in situ from Cp(2)ZrCl(2) and 2 equiv of n-BuLi, from which the S-bridged Ru-Zr dinuclear complexes CpRu(PPh(3))(C(triple bond)CPh)(mu-S)ZrCp(2) (4a) and CpRu(PPh(3))(C(triple bond)CPh)(mu-Se)ZrCp(2) (4b) were isolated, respectively. In these complexes, C-S(Se) bond cleavage of the alkynechalcogenolate ligands was promoted by "Cp(2)Zr", and the Zr atom was oxidized from II to IV. Treatment of 4a and 4b in THF under 1 atm CO gave rise to CpRu(CO)(C(triple bond)CPh)(mu-E)ZrCp(2) (E = S (5a), Se (5b)), while addition of tert-butyl isocyanide to a THF solution of 4b afforded CpRu(CN(t)()Bu)(C(triple bond)CPh)(mu-Se)ZrCp(2) (6). The crystal structures of 1a, 1c, 2a, 2b, 3, 4a, 4b, and 5b were determined by X-ray diffraction analysis.
Journal Article↗
Superior outcome of infant acute myeloid leukemia with intensive chemotherapy: results of the Japan Infant Leukemia Study Group.
This study analyzed data on 35 infants with acute myeloid leukemia (AML) who were treated with intensive chemotherapy between 1995 and 1998 in Japan. The incidence of boys, younger age (< 6 months old), and hyperleukocytosis at onset was high in patients with the M4/M5 subtype (n = 23) in the French-American-British classification, compared with the non-M4/M5 subtype (n = 12). Thirteen (56%) and 16 (70%) patients with the M4/M5 subtype also showed 11q23 translocations and MLL gene rearrangements, respectively, whereas only one patient with the non-M4/M5 subtype had this rearrangement. All 35 patients were treated with the ANLL91 protocol consisting of etoposide, high-dose cytarabine, and anthracyclines. Overall survival and the event-free survival (EFS) rates at 3 years of all patients were 76% (95% confidence interval [CI], 61.3%-90.7%) and 72% (95% CI, 56.4%-87.9%), respectively. EFS showed no significant difference between 2 subgroups divided by age, gender, presence of the MLL gene rearrangements, and white blood cell count at onset; EFS in patients with the M4/M5 subtype tended to be better than those with the non-M4/M5 subtype. Although all 6 patients who underwent allogeneic stem cell transplantation (SCT) have been in complete remission, no benefit of SCT was confirmed. These findings suggest that the intensive chemotherapy with the ANLL91 protocol might have been responsible for the observed good outcome of infant AML, even without SCT. The presence of the MLL gene rearrangements or the age at onset had no impact on the outcome of infant AML.
Aclarubicin↗
[Pulmonary embolism due to right atrial large thrombus quickly disappeared by intravneous thrombolysis].
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Aged↗