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S Kudo

Publications and source records attributed to S Kudo.

At least 91 records · Page 5Linked to original sources
PubMed2000

[Intra-arterial infusion chemotherapy with docetaxel for locally advanced breast cancer and inflammatory breast cancer].

From 1998 to 2000, we performed neoadjuvant intra-arterial infusion chemotherapy using docetaxel (60 mg/m2) a few times with 5 patients with local advanced breast cancer and inflammatory breast cancer. Therapeutic effects included 3 cases of PR among the breast tumor patients and downstaging was obtained 2 cases. No critical side effects were found due to this chemotherapy. We could perform mastectomy in all the cases. We consider intra-arterial infusion using docetaxel to be highly effective with few side effects in cases of advanced breast cancer.

Adenocarcinoma↗
PubMed2000

In vitro characterization of the oxidative cleavage of the octyl side chain of olanexidine, a novel antimicrobial agent, in dog liver microsomes.

The metabolism of olanexidine [1-(3,4-dichlorobenzyl)-5-octylbiguanide], a new potent biguanide antiseptic, was investigated in dog liver microsomes to characterize the enzyme(s) catalyzing the biotransformation of olanexidine to C-C bond cleavage metabolites. Olanexidine was initially biotransformed to monohydroxylated metabolite 2-octanol (DM-215), and DM-215 was subsequently oxidized to diol derivatives threo-2,3-octandiol (DM-221) and erythro-2,3-octandiol (DM-222). Diols were further biotransformed to a ketol derivative and C-C bond cleavage metabolite (DM-210, hexanoic acid derivative), an in vivo end product, in the incubation with dog liver microsomes. The formations of DM-215, DM-221, DM-222, and DM-210 followed Michaelis-Menten kinetics, and Eadie-Hofstee analysis of the metabolite formation activity confirmed single-enzyme Michaelis-Menten kinetics. The K(m) and V(max) values for the formation of DM-210 appeared to be 2.42 microM and 26.6 pmol/min/mg in the oxidation of DM-221 and 2.48 microM and 30.2 pmol/min/mg in the oxidation of DM-222. The intrinsic clearance (V(max)/K(m)) of the C-C bond cleavage reactions was essentially the same with either DM-221 or DM-222 as substrate. These oxidative reactions were significantly inhibited by quinidine, a selective inhibitor of CYP2D subfamilies, indicating the metabolic C-C bond cleavage of the octyl side chain of olanexidine to likely be mediated via the CYP2D subfamily in dog liver microsomes. This aliphatic C-C bond cleavage by cytochrome P450s may play an important role in the metabolism of other drugs or endogenous compounds possessing aliphatic chains.

Animals↗
PubMed1999

Association and dissociation properties of natural human interferon gamma.

The properties of natural human interferon gamma (IFN-gamma) molecules dissolved in protein-denaturing and non-denaturing solvents were examined by high-performance size-exclusion chromatography on a gel permeation column. IFN-gamma and tritium-labeled IFN-gamma molecules formed either dimers (>90.5%) with the molecular mass of 60 kDa or probably tetramers (<9.5%) with the molecular mass of approximately 100 kDa in non-denaturing solvents, and no monomer was detected. These oligomers were dissociated in protein-denaturing solvents such as 6 M guanidine hydrochloride, and IFN-gamma existed as monomers. There is no effect on formation of the monomer based on the dissociation of oligomers by acid treatment at pH 4.0. The monomers in protein-denaturing solvents formed dimers by association when applied to a column equilibrated with a non-denaturing solvent of phosphate buffer, pH 7.0. In conclusion, natural human IFN-gamma forms oligomers, particularly dimers, in non-denaturing solution, and this oligomer formation is a reversible reaction.

Cell Line↗
PubMed1999

Thallium-201 SPECT of adjacent intracranial tumours: a contrast in thallium kinetics.

We report a case of adjacent intracranial tumours: malignant fibrous histiocytoma (MFH) and meningioma. Thallium-201 single-photon emission computed tomography demonstrated different thallium kinetics between the tumours (slow washout from the MFH and rapid clearance in the meningioma) and could be said to have been useful for preoperative histological estimation.

Aged↗
PubMed1999

Sclerosing stromal tumor of the ovary: radiologic findings.

Sclerosing stromal tumor is a rare ovarian neoplasm. We describe the radiologic findings of sclerosing stromal tumor in two patients. In both patients, MR and CT images showed a large mass in the left adnexal region. On dynamic contrast-enhanced images, the tumors showed early peripheral enhancement with centripetal progression.

Adult↗
PubMed1999

Retropharyngeal rhabdomyosarcoma mimicking pseudotumor cerebri.

A 6-year-old male presented with headache, vomiting, visual obscuration, and papilledema. Clinical presentation, initial laboratory data, and radiologic evaluation suggested a diagnosis of pseudotumor cerebri. The development of lower cranial nerve palsies after transient resolution of symptoms prompted reassessment of the diagnosis, which revealed retropharyngeal rhabdomyosarcoma involving the right jugular vein. Cerebral angiography demonstrated the complete venous occlusion at the jugular foramen. Careful neurologic follow-up is essential in a patient with pseudotumor cerebri or idiopathic intracranial hypertension.

Cerebral Angiography↗
PubMed1999

Significance of hematoma size for evaluating the grade of blunt renal trauma.

BACKGROUND: The hematoma size relative to the body size was measured on computed tomography films using a personal computer system in order to define whether that parameter is useful for decision-making in the management of blunt renal trauma. METHODS: From 1982 to 1997, 33 patients with intermediate or severe grade blunt renal trauma were retrospectively divided into three groups: group 1, managed conservatively without transcatheter embolization; group 2, managed by bedrest after selective transcatheter embolization; and group 3, managed operatively. In these three groups, the hematoma area (H) and the ratio of hematoma area to body area on CT (H/B) were measured and the chronological changes of the H/B in groups 1 and 2 were studied. RESULTS: The H and H/B of group 3 were significantly larger than those of group 1. The H/B was more clearly distinguished for each group compared with the H alone. Well-preserved kidney integrity, despite the presence of a large hematoma in group 2, allowed the conservative treatment following transcatheter embolization of the bleeding site. The H/B of all group 1 patients gradually decreased and on the 40th or 50th day after injury they reached a level equivalent to the ratio of contra-lateral normal kidney area to body area. CONCLUSION: The ratio of hematoma area to body area on CT was very useful in evaluating the grade of blunt renal trauma. In conservative treatment for blunt renal trauma changes of the hematoma size is a useful indicator for management.

Adolescent↗
PubMed1999

Pharmacokinetics of natural human IFN-alpha in hemodialysis patients.

A pharmacokinetic study of natural human interferon-alpha (IFN-alpha) was conducted in hemodialysis patients. Natural human IFN-alpha was intramuscularly (i.m.) administered to 8 hemodialysis patients at a single dose of 5 million IU and to 7 patients undergoing hemodialysis at the same dose once daily for 5 successive days. The serum antiviral activity was determined by a cytopathic effect bioassay. In the single dose study, the serum antiviral activity reached a maximum (Cmax) of 56.4 +/- 33.3 IU/ml at 8.3 +/- 2.7 h after dosing, and the area under the serum concentration-time curve (AUC0-24h) was 957.2 +/- 601.8 IU h/ml. The Cmax and AUC0-24h values at day 5 following the repeated dosing were both 2.6-fold higher than those of day 1, and the serum antiviral activity reached a steady state within 3 days after initiation of repeated administration. The serum antiviral activity in hemodialysis patients showed a tendency to increase compared with that in the subjects with normal renal function, but the magnitude of the differences was not great. In one nonhemodialysis patient with poor renal function (creatinine clearance < 30 ml/min), no increases in serum antiviral activity owing to repeated dosing were observed. The main adverse events seen were fever (4 of 13, 30.8%), leukopenia (3 of 13, 23.1%), and fatigue (2 of 13, 15.4%). These results suggest that dosage modifications of natural human IFN-alpha are unnecessary for patients with low renal function, even those undergoing hemodialysis.

Aged↗
PubMed1999

Intrarenal handling of recombinant human interleukin-1alpha in rats: mechanism for proximal tubular protein reabsorption.

The intrarenal distribution of recombinant human interleukin (IL)-la was studied in Sprague-Dawley male rats by immunohistochemical staining. The effects of the concurrent administration of various proteins or synthetic polypeptides on the urinary excretion of IL-1alpha were also studied to clarify the mechanism(s) for the reabsorption of IL-la in the renal tubules. Microscopic immunohistochemistry showed that IL-1alpha distributed to early proximal convoluted tubules but not to glomeruli, Henle's loops, distal tubules, or collecting ducts. Electron microscopic immunohistochemistry showed that IL-la was taken up into the endocytic vesicle located close to the apical membrane of the proximal tubular epithelial cells, then accumulated in lysosomes. Urinary excretion of intravenous IL-la at 500 microg/kg was extremely low, accounting for only 0.014% of the dose administered. The coadministration of intravenous human serum albumin did not affect the urinary excretion of IL-1alpha, whereas trypsinogen, myoglobin, and trypsin inhibitor dose-dependently produced an increase in the excretion of IL-la, the potency of which was greatest in that order. Poly-L-lysine, but not poly-L-glutamic acid dose-dependently increased the urinary excretion of IL-1alpha. These results indicate that most of the glomerular filtrated IL-1alpha could be easily reabsorbed into the proximal tubular cells via endocytosis, and the reabsorption was inhibited by coadministered low molecular weight proteins, particularly basic proteins. This result suggests that scavengers with a negative charge and broad binding ability for glomerular filtered proteins exist on the surface of the apical membrane of proximal tubular cells and play an important role in the reabsorption of filtered proteins.

Absorption↗
PubMed1999

Role of interleukin-1beta in the modulations of cytochrome P450 and heme metabolism in rat liver.

The effect of recombinant human interleukin-1beta (IL-1beta) on the modulation of hepatic cytochrome P450 (P450) was investigated by in vivo subcutaneous dosing studies in male Sprague-Dawley rats. To assess the effect of IL-1beta on heme metabolism, we determined the delta-aminolevulinic acid synthetase (delta-ALAS) and heme oxygenase activities in the liver. IL-1beta suppressed the microsomal total P450 and heme contents and delta-ALAS activity in the liver. In contrast, microsomal heme oxygenase activity was significantly increased by the IL-1beta treatments. Western blot analysis and marker enzyme activities for individual P450 isoforms demonstrated that IL-1beta suppressed CYP2C6, 2C13, 2E1, and 3A2, whereas CYP2A, 2B1/2, 2C11, and 4A1 were not influenced by the treatments. IL-1beta inhibited both allylisopropylamide- and phenobarbital-inducible delta-ALAS activities in the liver. These results indicate that IL-1beta has differential effects on the constitutive P450, and also on delta-ALAS and heme oxygenase activities in rat liver. Thus, the modulation of hepatic P450 by IL-1beta is complex, and IL-1beta may be involved in the regulation of both apoprotein synthesis for each P450 isoform and the heme pools in the liver.

5-Aminolevulinate Synthetase↗
PubMed1999

Proteases involved in the metabolic degradation of human interleukin-1beta by rat kidney lysosomes.

The in vitro metabolic degradation of human interleukin (IL)-1beta was studied using lysates of rat kidney lysosomes, and proteases involved in the degradation were identified. In the study of IL-1beta degradation, fluorescein isothiocyanate (FITC)-labeled IL-1beta was used as a substrate. The maximal degradation of IL-1beta occurred at pH 3.0, and the reaction was proportional to the lysosomal protein concentration and time of incubation. The degradation was stimulated by the addition of L-cysteine. The reaction was not inhibited by phenylmethanesulfonyl fluoride or EDTA, indicating that serine proteases or metalloproteases do not play a major role in the degradation process. N-Ethylmaleimide, leupeptin and E-64, inhibitors of thiol protease, inhibited the degradation of IL-1beta, by 59%-70%. Pepstatin A, an inhibitor of carboxyl protease, inhibited the degradation by 58%. Combinations of thiol and carboxyl protease inhibitors nearly completely inhibited the degradation. Bio-Gel P-10 gel filtration chromatography of in vitro reactants confirmed the ability of lysosomal proteases to degrade IL-1beta and revealed four to five peaks of degradation products. Taken together, these results indicate that thiol protease and carboxyl protease play an important role in the IL-1beta degradation process by kidney lysosomes. Leupeptin and E-64 dose dependently inhibited both cathepsin B and cathepsin L activities, and pepstatin A strongly inhibited cathepsin D activity in rat kidney lysosomes. The present results suggest that cathepsin B, cathepsin L, and cathepsin D in kidney lysosomes are involved in the metabolic degradation of human IL-1beta.

Animals↗
PubMed1999

A study on the effects of endogenous nitric oxide on coronary blood flow, myocardial oxygen extraction and cardiac contractility.

The purpose of the present study was to clarify how endogenous nitric oxide (NO) affects cardiac contractility and myocardial oxygen consumption (MVO2) in vivo. alpha-Chloralose-anesthetized dogs (n = 18) were instrumented to perform continuous and simultaneous measurements of coronary blood flow (CBF), anterior interventricular vein oxygen saturation (with the use of a fiberoptic catheter), aortic pressure, left ventricular pressure, and left ventricular volume. CBF, myocardial oxygen extraction (O2-extract), MVO2, the relationship between CBF and O2-extract during direct vasodilation induced by intracoronary papaverine (0.1, 0.2, 0.4 mg/kg), and cardiac contractility (Emax) were examined at control, after intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA, 2 mg/kg) and after antagonization of NO by L-arginine (20 mg/kg). L-NMMA decreased CBF from 62.0 +/- 1.7 to 59.7 +/- 2.4 (mL/min/100 g, P < 0.05) and increased O2-extract from 68.2 +/- 1.7 to 79.0 +/- 1.7% (P < 0.05). Emax was increased after L-NMMA from 3.2 +/- 0.2 to 3.7 +/- 0.1 (mmHg/mL/100 g, P < 0.05). These effects of L-NMMA were antagonized by L-arginine (P < 0.05 vs. after L-NMMA, P = NS vs. before L-NMMA). L-NMMA shifted CBF and O2-extract relationship determined by papaverine injection upward and L-arginine antagonized it to its baseline level. Endogenous NO reduces cardiac contractility and decreases MVO2, while increasing CBF.

Animals↗
PubMed1999

Methylation-mediated transcriptional silencing in euchromatin by methyl-CpG binding protein MBD1 isoforms.

DNA methylation of promoter-associated CpG islands is involved in the transcriptional repression of vertebrate genes. To investigate the mechanisms underlying gene inactivation by DNA methylation, we characterized a human MBD1 protein, one of the components of MeCP1, which possesses a methyl-CpG binding domain (MBD) and cysteine-rich (CXXC) domains. Four novel MBD1 isoforms (MBD1v1, MBD1v2, MBD1v3, and MBD1v4) were identified by the reverse transcription-PCR method. We found that these transcripts were alternatively spliced in the region of CXXC domains and the C terminus. Green fluorescent protein-fused MBD1 was localized to multiple foci on the human genome, mostly in the euchromatin regions, and particularly concentrated in the pericentromeric region of chromosome 1. Both the MBD sequence and genome methylation were required for proper localization of the MBD1 protein. We further investigated whether MBD1 isoforms are responsible for transcriptional repression of human genes. A bacterially expressed MBD1 protein bound preferentially to methylated DNA fragments containing CpG islands from the tumor suppressor genes p16, VHL, and E-cadherin and from an imprinted SNRPN gene. All MBD1 isoforms inhibited promoter activities of these genes via methylation. Interestingly, MBD1 isoforms v1 and v2 containing three CXXC domains also suppressed unmethylated promoter activities in mammalian cells. These effects were further manifested in Drosophila melanogaster cells, which lack genome methylation. Sp1-activated transcription of methylated p16 and SNRPN promoters was inhibited by all of the MBD1 isoforms, whereas the isoforms v1 and v2 reduced Sp1-activated transcription from unmethylated promoters as well. These findings suggested that the MBD1 isoforms have different roles in methylation-mediated transcriptional silencing in euchromatin.

Alternative Splicing↗
PubMed1999

Successful autotransplantation of microvessel fragments into the rat heart.

We examined whether microvessel fragments (Mvf), autologously transplanted with myofibroblasts (Mf) into the heart, could survive and form connections to the host's coronary microcirculation. Neither achievement has been reported before in the heart. Mvf and Mf were prepared from Sprague-Dawley rat epididymal fat pads. A mixture of Mvf (labeled with the fluorescent probe DiI-acetylated low-density lipoprotein, DiI-Ac-LDL) and Mf was injected into the superficial myocardium under general anesthesia. Rats (n = 5 in each group) were killed on postoperative days 7, 14, 21, 42 and 49, and India ink was perfused through the coronary arteries. Frozen sections of the injected area were examined under fluorescence and light microscopes. Some DiI-Ac-LDL-labeled Mvf survived in each group, and India ink was present in the lumina of microvessels coincident with DiI-Ac-LDL-labeled autotransplanted Mvf. Hematoxylin and eosin staining revealed mild inflammatory reactions followed by some fibrosis at the injection sites. These findings indicate that autotransplanted Mvf can survive for at least 49 days, and that patent microvascular anastomoses can form between them and the host's coronary microvessels. Possibly, autotransplantation of Mvf could lead to the development of a new collateral microcirculation, a phenomenon especially important in the ischemic heart.

Animals↗
PubMed1999

Oral administration of soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS) reduces ischemic damage in the gerbil hippocampus.

Mongolian gerbils orally administered with soybean lecithin transphosphatidylated phosphatidylserine (SB-tPS, 240 mg/kg) for 5 days were subjected to cerebral ischemia by bilateral common carotid artery occlusion. The pyramidal cell damage of the hippocampal CA1 subfield was classified into 4 grades according to the proportion of damaged neurons on the tenth day after the ischemic treatment. The damage score of the SB-tPS group was statistically less than that of the control group. This suggests that the pre-administration of SB-tPS may relieve the delayed neuronal cell death caused by cerebral ischemia.

Administration, Oral↗
PubMed1999

Pharmacokinetics of haloperidol: an update.

Haloperidol is commonly used in the therapy of patients with acute and chronic schizophrenia. The enzymes involved in the biotransformation of haloperidol include cytochrome P450 (CYP), carbonyl reductase and uridine diphosphoglucose glucuronosyltransferase. The greatest proportion of the intrinsic hepatic clearance of haloperidol is by glucuronidation, followed by the reduction of haloperidol to reduced haloperidol and by CYP-mediated oxidation. In studies of CYP-mediated disposition in vitro, CYP3A4 appears to be the major isoform responsible for the metabolism of haloperidol in humans. The intrinsic clearances of the back-oxidation of reduced haloperidol to the parent compound, oxidative N-dealkylation and pyridinium formation are of the same order of magnitude, suggesting that the same enzyme system is responsible for the 3 reactions. Large variation in the catalytic activity was observed in the CYP-mediated reactions, whereas there appeared to be only small variations in the glucuronidation and carbonyl reduction pathways. Haloperidol is a substrate of CYP3A4 and an inhibitor, as well as a stimulator, of CYP2D6. Reduced haloperidol is also a substrate of CYP3A4 and inhibitor of CYP2D6. Pharmacokinetic interactions occur between haloperidol and various drugs given concomitantly, for example, carbamazepine, phenytoin, phenobarbital, fluoxetine, fluvoxamine, nefazodone, venlafaxine, buspirone, alprazolam, rifampicin (rifampin), quinidine and carteolol. Overall, drug interaction studies have suggested that CYP3A4 is involved in the biotransformation of haloperidol in humans. Interactions of haloperidol with most drugs lead to only small changes in plasma haloperidol concentrations, suggesting that the interactions have little clinical significance. On the other hand, the coadministration of carbamazepine, phenytoin, phenobarbital, rifampicin or quinidine affects the pharmacokinetics of haloperidol to an extent that alterations in clinical consequences would be expected. In vivo pharmacogenetic studies have indicated that the metabolism and disposition of haloperidol may be regulated by genetically determined polymorphic CYP2D6 activity. However, these findings appear to contradict those from studies in vitro with human liver microsomes and from studies of drug interactions in vivo. Interethnic and pharmacogenetic differences in haloperidol metabolism may explain these observations.

Antipsychotic Agents↗
PubMed1999

Production of menaquinones by lactic acid bacteria.

Lactic acid bacteria were examined for their ability to produce quinone compounds, which may include dietary sources of menaquinones. Isoprenyl quinones in bacterial cells grown in a synthetic medium were extracted and analyzed by thin layer chromatography. Lactococcus lactis ssp. cremoris (three strains), Lactococcus lactis ssp. lactis (two strains), and Leuconostoc lactis were selected as high producers of quinone that synthesized more than 230 nmol of quinones/g of dried cells. The quinones were presumed to be menaquinone-7 to -10 by high performance liquid chromatography. Precise molecular weights were determined by mass spectrometry for Lactococcus lactis ssp. cremoris YIT 2011 and Leuconostoc lactis YIT 3001 and identified as menaquinone-8 and -9 for the former and menaquinone-9 and -10 for the latter. Those strains, when grown either in reconstituted nonfat dry milk or a soymilk medium, produced a beneficial quantity for dietary supplement (i.e., 29 to 123 micrograms of menaquinones/L of the fermented medium).

Benzoquinones↗