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Biomedical subjects

T Kishi

Publications and source records attributed to T Kishi.

At least 55 records · Page 3Linked to original sources

[Clinical trial of prophylactic hepatic arterial chemotherapy for liver metastases in patients with Dukes' C colorectal cancer].

Preliminary results of a prospective non-randomized trial of prophylactic hepatic arterial chemotherapy for liver metastases from colorectal cancer are presented. Twenty-two colorectal cancer patients (infusion group) in Dukes' C stage were given hepatic arterial infusion of 5-FU (500 mg/body for 1 hr per week, repeated 50 times) and peroral UFT-E (2.0 g/body, daily). Informed consent was obtained from all patients. Adverse effects and postoperative recurrence in the infusion group were compared with those of patients with UFT-E alone (control group). Complications related to hepatic arterial infusion in the infusion group were also demonstrated. There was no adverse effect in the control group, while diarrhea (grade 1) developed in one patient (5%) and pigmentation in five (24%) in the infusion group. Complications related to infusion were found in five patients (5%). Three patients in the infusion group presented with metachronous hepatic lesions, two of which were resected successfully. In the control group, one patient died of marked hepatic metastases, and one developed ovarian metastasis with lymph node involvement. Our regimen appears hematologically safe, however, the high frequency of pigmentation should be kept in mind. The oncological benefit of this chemotherapy would be clarified by a larger series of cases and longer follow-up.

Administration, Oral↗

An essential function of Grr1 for the degradation of Cln2 is to act as a binding core that links Cln2 to Skp1.

In budding yeast, SCF complexes, composed of Skp1, Cdc53 and one of the F-box proteins, have been implicated in Cdc34-dependent ubiquitination. Grr1, which is required for degradation of G1 cyclins Cln1 and Cln2 as well as for regulation of glucose repression, is an F-box protein and interacts with Skp1 through the F-box motif. Grr1 also interacts in vitro with phosphorylated Cln1 and Cln2. However, ubiquitination of Cln1 has not been successful in an in vitro reconstituted system. In this study, domain analysis was performed to understand the role of Grr1 in the degradation of Cln2. Grr1 has another motif, leucine-rich repeats (LRR), in addition to the F-box. We found that the LRR is a domain for Cln2 binding. A deletion of half of the LRR abolished the interaction of Grr1 with phosphorylated Cln2 but not with Skp1 in vivo, and a deletion of the F-box abolished the interaction of Grr1 with Skp1 but not with phosphorylated Cln2 in vivo. Based on these results, we constructed grr1 mutants that are defective in association with either Skp1 or Cln2. Cln2 was highly stabilized and accumulated in the phosphorylated forms in the mutant cells. Furthermore, Skp1 associated in vivo with phosphorylated Cln2 in a Grr1-dependent manner. These data suggest that Grr1 is required for degradation of Cln2 through linking phosphorylated Cln2 to Skp1 in a SCFGrr1 complex.

Carrier Proteins↗

Tectal projections to the parvicellular reticular formation and the upper cervical spinal cord in the rat, with special reference to axon collateral innervation.

After Phaseolus vulgaris leucoagglutinin injection into the lateral part of the superior colliculus (SC) in the rat, labeled fibers and axon terminals in the lower brainstem were distributed not only in the medial reticular formation but also in the lateral tegmental field including the parvicellular reticular formation (RFp). More caudally, in the upper cervical spinal cord labeled fibers with bouton-like varicosities were distributed mainly in laminae V, VII and VIII, with relatively sparse distribution in lamina IX. These labeled axons were found bilaterally with a clear-cut contralateral dominance. After combined injections of rhodamine-dextranamine, Fluoro-ruby (FR) into the RFp and Fluoro-gold (FG) into the upper cervical spinal cord on the same side, SC neurons labeled with FR were intermingled with those labeled with FG in the lateral part of the SC contralateral to the injection sites. In the stratum griseum intermediale, some of them were double-labeled with both tracers. Our results suggest that SC neurons innervating both the RFp and the cervical spinal cord may be involved in the coordination of head and mouth movements.

Animals↗

Developmental appearance of oligodendrocytes in the embryonic chick retina.

The axons of the optic nerve layer are known to be myelinated by oligodendrocytes in the chick retina. The development of the retinal oligodendrocytes has been studied immunohistochemically with antibodies against oligodendrocyte lineage: monoclonal antibodies O4 and O1, and an antibody against myelin basic protein. O4 positive (O4+) cells were first detected in the retina on the tenth day of incubation (embryonic day (E)10, stage 36). The labeled cells were located in the optic nerve layer close to the optic fissure. Most were unipolar in shape, extending a leading process with a growth cone toward the periphery of the retina. By E12, unipolar O4+ cells had spread to the middle of the retina. Many O4+ cells close to the optic fissure showed radial arrangement with extension of processes toward the inner limiting membrane. O1+ oligodendrocytes were first observed in the E14 retina positioned just above (interiorly to) retinal ganglion cells. These labeled cells extended fine processes in the optic nerve layer. Limited numbers of myelin basic protein-positive cells were present by E16 and located interiorly to the retinal ganglion cells. In addition to the oligodendrocyte in the optic nerve layer, a limited number of O4+ cells were observed in the inner nuclear layer by E14, and they became O1+ by E18. Furthermore, explant culture experiments showed E10 to be the youngest stage at which the retina contained oligodendrocyte precursors. An intraventricular inj ection of fluorescent dye 1,1',dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate (DiI) at E6 yielded O4+/DiI+ cells in the retina at E10, which provided direct evidence to support migration of oligodendrocyte precursor into the retina. The present results demonstrated the sequential appearance of the cells of oligodendrocyte lineage and the detailed morphology of the developing oligodendrocytes in the retina. These morphologic features strongly suggested that retinal oligodendrocytes were derived from the optic nerve and spread by migration through the optic nerve layer.

Animals↗

Application of capillary electrophoresis for the determination of inorganic ions in trace explosives and explosive residues.

Capillary electrophoresis was developed for the analysis of low explosive residue, because a significant amount of inorganic anions and cations remain after deflagration. Certain high explosives, such as emulsion explosives, produce a vast quantity of inorganic ions after a blast and can readily be analyzed using capillary electrophoresis. Often, trace amounts of explosive residues may be present on physical evidence submitted in criminal cases. Trace amounts of inorganic ions such as nitrate, chlorate, and ammonium may be detected using capillary electrophoresis owing to the low detection limit of these species. The utility of capillary electrophoresis in the analysis of explosive residues is in its ability to simultaneously analyze trace explosives and ionic products present on physical evidence.

Anions↗

Oxygen consumption and motility of mechanically unloaded myocardial slices.

We have recently established a new measurement system of myocardial O2 consumption per min (mVO2) of mechanically unloaded rat left ventricular (LV) slices (Yasuhara et al.: Am. J. Physiol. 270: H1063-H1070, 1996). Using this system, we have revealed that an increment in O2 consumption (delta mVO2) by electrical stimulation primarily represents mVO2 for Ca2+ handling in the excitation-contraction (E-C) coupling, though much smaller than that in the whole heart preparation. The much smaller delta mVO2 in the sliced myocardium than that in the whole heart is due to the much lower frequency of stimulation (60 bpm against 300 bpm). We consider that delta mVO2 does not contain mVO2 for residual crossbridge cycling from the results showing no effect of 2,3-butanedione monoxime on delta mVO2 despite the large decrease in mechanically unloaded contraction, which is expressed by the motility index. We also revealed that mVO2 without stimulation represents basal metabolism. The basal metabolism in rat myocardial slices, which is much higher than in other mammalian hearts, corresponds to that in the rat whole heart preparation. We finally obtained the results showing that sarcoplasmic reticulum (SR) Ca2+ pump blockers, thapsigargin and cyclopiazonic acid, did not reduce basal metabolic mVO2 but both of them reduced delta mVO2 maximally by 50-70% of control and markedly reduced the motility index. We conclude that myocardial O2 consumption (VO2) is composed of VO2 for E-C coupling and basal metabolism and does not contain VO2 for residual crossbridge cycling. Basal metabolic VO2 does not include VO2 for the SR Ca2+ pump, and at least two-thirds of VO2 for E-C coupling represents VO2 for the SR Ca2+ pump.

Animals↗

Grr1 functions in the ubiquitin pathway in Saccharomyces cerevisiae through association with Skp1.

Cdc34, a ubiquitin-conjugating enzyme in Saccharomyces cerevisiae, is required for cell cycle progression. sic1, an S-phase cyclin-dependent kinase (CDK) inhibitor, is a critical target of Cdc34-mediated ubiquitination. Other essential target protein(s) could be defined since cdc34 sic1 double mutants still arrest in G2 phase. To identify proteins which function in the Cdc34-dependent ubiquitin pathway, a series of extragenic suppressors of the cdc34-1 sic1 double mutations was isolated. One of them was found to be defective in GRR1, which is involved not only in glucose repression but also in G1 cyclin destabilization. However, neither lack of glucose repression nor stabilization of G1 cyclin caused the suppression of cdc34-1 sic1. Conversely, Grr1 overproduction in cdc34-1 sic1 cells impaired colony formation, even at the permissive temperature. A multicopy suppressor, MGO1, which rescued the growth defect associated with Grr1 overproduction was isolated, and found to be identical to SKP1. Furthermore, Grr1 bound Skp1 directly in vitro. These results strongly suggest that Grr1 functions in the ubiquitin pathway through association with Skp1.

Anaphase-Promoting Complex-Cyclosome↗

Bone responses at various skeletal sites to human parathyroid hormone in ovariectomized rats: effects of long-term administration, withdrawal, and readministration.

This study was undertaken to examine bone responses to human parathyroid hormone (hPTH) at various skeletal sites. Forty 6-month-old female Wistar rats were divided into four groups, and bilateral ovariectomy (ovx) was performed in three of the four groups (n=30). The other group (n=10) received sham surgery (sham). Four weeks after the ovx, hPTH(1-34) administration was started. The ovx rats received 5 microg/kg per day of PTH (PTH-5; n=10), 10 microg/kg per day of PTH (PTH-10; n=10), or vehicle (PTH-v; n=10), three times a week for 24 weeks. Thereafter, PTH was withdrawn for 16 weeks followed by readministration at the same dosage for 8 weeks. The bone mineral content (BMC) at the whole skeleton and the bone mineral density (BMD) at the lumbar vertebrae, caudal vertebrae, distal femur, diaphysis of the femur, proximal tibia, and skull were longitudinally measured by dual-energy x-ray absorptiometry (DXA) at 4-week intervals during the experimental period. Thirteen rats that died during the experimental period were excluded from the analysis. As a result, the whole skeleton showed an increase in BMC during the PTH administration, whereas no withdrawal or readministration effects were observed. The metaphysis showed a highly sensitive bone response, while the lumbar vertebrae and diaphysis showed a moderate magnitude of changes in bone mass during the PTH administration. The skull and the caudal vertebrae did not show sensitive responses to PTH. After withdrawal, the BMD was markedly decreased at the sites that showed marked increases in BMD after PTH administration. The PTH readministration increased the BMD again at the sites that showed sensitive responses after the initial administration. Strength tests were also performed when the readministration was completed. The ultimate loads for the femur and vertebral body in the PTH-treated groups were significantly higher than those in the vehicle-treated group. In conclusion, the response to PTH in ovx rats varied among skeletal sites; withdrawal-related decreases were marked at the sites showing marked increases in bone mass related to PTH administration, and PTH readministration may be sufficiently effective.

Absorptiometry, Photon↗

Thrombosed varix in the submandibular space.

Thrombosed varix in the oral region often appears as a pigmented mass in the mucosa simulating a hemangiomatous lesion. It rarely occurs in the deeper orofacial region. We report a case of thrombosed varix in the submandibular space with symptoms of a tumor. The clinical symptoms and MRI and CT findings are discussed. The clinical symptoms were not characteristics. High signal intensity on CT (80 HU) and a concentric signal distribution on CT and MRI may suggest a thrombosed varix.

Chin↗

Cloning, sequencing, and disruption of the Bacillus subtilis psd gene coding for phosphatidylserine decarboxylase.

The psd gene of Bacillus subtilis Marburg, encoding phosphatidylserine decarboxylase, has been cloned and sequenced. It encodes a polypeptide of 263 amino acid residues (deduced molecular weight of 29,689) and is located just downstream of pss, the structural gene for phosphatidylserine synthase that catalyzes the preceding reaction in phosphatidylethanolamine synthesis (M. Okada, H. Matsuzaki, I. Shibuya, and K. Matsumoto, J. Bacteriol. 176:7456-7461, 1994). Introduction of a plasmid containing the psd gene into temperature-sensitive Escherichia coli psd-2 mutant cells allowed growth at otherwise restrictive temperature. Phosphatidylserine was not detected in the psd-2 mutant cells harboring the plasmid; it accumulated in the mutant up to 29% of the total phospholipids without the plasmid. An enzyme activity that catalyzes decarboxylation of 14C-labeled phosphatidylserine to form phosphatidylethanolamine was detected in E. coli psd-2 cells harboring a Bacillus psd plasmid. E. coli cells harboring the psd plasmid, the expression of which was under the control of the T7phi10 promoter, produced proteins of 32 and 29 kDa upon induction. A pulse-labeling experiment suggested that the 32-kDa protein is the primary translation product and is processed into the 29-kDa protein. The psd gene, together with pss, was located by Southern hybridization to the 238- to 306-kb SfiI-NotI fragment of the chromosome. A B. subtilis strain harboring an interrupted psd allele, psd1::neo, was constructed. The null psd mutant contained no phosphatidylethanolamine and accumulated phosphatidylserine. It grew well without supplementation of divalent cations which are essential for the E. coli pssA null mutant lacking phosphatidylethanolamine. In both the B. subtilis null pss and psd mutants, glucosyldiacylglycerol content increased two- to fourfold. The results suggest that the lack of phosphatidylethanolamine in the B. subtilis membrane may be compensated for by the increases in the contents of glucosyldiacylglycerols by an unknown mechanism.

Amino Acid Sequence↗

Effect of arylthiolated 2,3-dimethoxy-1,4-benzoquinones on respiratory activity and lipid peroxidation in bovine heart mitochondria.

A series of arylthiolated 2,3-dimethoxy-1,4-benzoquinones was synthesized and tested for the effect on the respiratory system and the lipid peroxidation in bovine heart mitochondria (BHM). These quinones showed intense inhibitory activities on the respiratory system in BHM. Their inhibitory activity in the succinate oxidase system was greater than that in the NADH oxidase system. No difference between the difference spectra, with and without these quinones, of the reduced minus oxidized forms of cytochromes (cyt.) suggested that these quinones inhibit at the site after cyt. a+a3 in the respiratory chain. Moreover, these quinones were as efficient as exogenous ubiquinone-10 (UQ-10) for the inhibition of lipid peroxidation. 5- And 5,6-di-arylthio groups on the quinone ring were found to be favorable for inhibition of the respiratory system and lipid peroxidation. Our results suggest that arylthiolated 2,3-dimethoxy-1,4-benzoquinones act as antioxidants by increasing the amount of endogenous reduced UQ-10 in BHM.

Animals↗

A simple fluorometric determination of vitamin C.

A simple and accurate method for determination of vitamin C (ascorbic acid (AsA) and dehydroascorbic acid (DHA)) using 4,5-dimethyl-o-phenylenediamine (DMPD) was investigated. It was found that DMPD is a useful fluorescent reagent. The reaction product of DMPD with DHA showed strong and stable fluorescence (Ex; 360 nm, Em; 440 nm). Fluorometric derivatives were extracted with isobutanol or n-butanol. Extraction with isobutanol was superior to that with n-butanol in terms of specificity, since fluorometric derivatives of keto acids were extracted with n-butanol, together with DHA. The fluorescence intensity of DMPD derivatives was absolutely stable in isobutanol for at least 24 h. The sensitivity of determination of vitamin C was improved by removing several non-fluorometric compounds coexisting in the samples. The derivative derived from AsA was easily separated from those of keto acids by an HPLC method. The determination of vitamin C in natural products was thus improved by extraction and the HPLC method.

1-Butanol↗

Histopathological and immunohistochemical studies on experimental asthmatic model induced by aerosolized ovalbumin inhalation in guinea pigs.

To establish an animal model of asthma, fully sensitized guinea pigs inhaled aerosolized ovalbumin after booster treatments. At 0, 1, 3, 6, 24 and 48 hr after provocation (hap), histopathological and immunohistochemical changes in the airways of guinea pigs were examined. From 1 to 6 hap, anaphylactic changes such as perivascular edema and bronchoconstriction were detected. After that, intensive infiltration of eosinophils appeared and lasted until 48 hap. Temporal increases in the number of apoptotic cells and proliferating cell nuclear antigen positive cells were detected in the alveoli after the provocation. These findings suggest that this animal model showing both immediate and late asthmatic responses may be useful as an asthmatic model.

Administration, Inhalation↗

Unloaded skeletal muscle O2 uptake decreases with decreased venous PO2 at high-frequency stimulation.

The aim of the present study was to clarify the effects of O2 diffusion limitation resulting from hypoxic interventions on O2 uptake (V.O2) in unloaded (that is, near-zero initial force) and loaded skeletal muscle in a high-frequency stimulation. We measured V.O2, muscle venous PO2 (PvO2) and initial force in gastrocnemius-plantaris muscle in situ of anesthetized dogs: (1) during hypoxic hypoxia at 1 Hz tetanic stimulation, and (2) during hypoxia induced by the perfusion with high O2-affinity erythrocytes (having a low value of PO2 at 50% saturation of hemoglobin (P50)) at 4 Hz twitch stimulation. Averaged unloaded V.O2 during normoxia was 10.2 ml.min-1.100 g-1 at averaged blood flow of 74 ml.min-1.100 g-1 (n = 6). Hypoxic hypoxia of a decreased O2 delivery (arterial O2 concentration x flow) significantly decreased both unloaded and loaded V.O2 with a decrease in PvO2 (p<0.05). The unloaded V.O2 was reduced to 8.5 ml.min-1.100 g-1. Low P50-hypoxia decreased V.O2 at high and low initial force conditions with a decrease in PvO2 (p<0.05) at the same O2 delivery. If these decreases in V.O2 correspond with a decrease in V.O2 at zero initial force (unloaded V.O2), the unloaded V.O2 value is calculated to be 7.57 ml.min-1.100 g-1 from V. O2-initial force data. Despite the different conditions of O2 delivery, the unloaded V.O2 decreased by both hypoxia showed similar values. Thus the decreased unloaded V.O2 does not seem to be derived from only the limited O2 delivery. Some other factors such as the limitation of O2 diffusion may contribute to the decreased V.O2.

Animals↗

[Intra-arterial infusion chemotherapy for unresectable or recurrent breast cancer].

Epirubicin and 5-FU were administered through an indwelling catheter inserted into the internal mammary artery and/or subclavian artery employing an implantable infusion port system for the treatment of unresectable advanced breast cancer and recurrent breast cancer. Intraarterial infusion chemotherapy proved to be an effective treatment modality for unresectable advanced breast cancer and recurrent breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Comparative study of technetium-99m-sestamibi and thallium-201 SPECT in predicting chemotherapeutic response in small cell lung cancer.

UNLABELLED: The purpose of this study was to evaluate the relationship between 99mTc-sestamibi (MIBI) accumulation by tumor and response to chemotherapy in small cell lung cancer patients compared with 201TI-chloride. METHODS: There were 19 patients with small cell lung cancer just before chemotherapy initiation. The patients were classified by a follow-up CT into complete remission, partial remission and no change groups. All patients underwent dual-isotope imaging with 201TI-chloride and 99mTc-MIBI. Regions of interest were placed over the tumors and contralateral normal lung tissue on one coronal view with a clearly defined lesion, and the tumor-to-normal (T/N) ratio and retention index were calculated. RESULTS: Early and delayed T/N ratios for 99mTc-MIBI in complete remission and partial remission groups were significantly higher (p < 0.05) than in the no change group. There was no significant correlation between T/N ratio and tumor response using 201TI-chloride. There were no significant differences in the retention index with respect to the tumor response in both 201TI-chloride and 99mTc-MIBI SPECT images. CONCLUSION: Technetium-99m-MIBI SPECT may be more effective than 201TI-chloride SPECT for evaluating response to chemotherapy in patients with small cell lung cancer.

Adult↗