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Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 379 records · Page 21Linked to original sources

Gap junction systems in the rat vestibular labyrinth: immunohistochemical and ultrastructural analysis.

The distribution of gap junctions within the vestibular labyrinth was investigated using immunohistochemistry and transmission electron microscopy. Connexin26-like immunoreactivity was observed among supporting cells in each vestibular sensory epithelium. Reaction product was also present in the transitional epithelium of each vestibular endorgan and in the planum semilunatum of crista ampullaris. No connexin26-like immunoreactivity was observed among thin wall epithelial cells or among vestibular dark cells. In addition, fibrocytes within vestibular connective tissue were positively immunostained. Reaction product was also detected in the melanocyte area just beneath dark cells. Ultrastructural observations indicated that a gap junction network of vestibular supporting cells extends to the transitional epithelium and planum semilunatum and forms an isolated epithelial cell gap junction system in each vestibular endorgan. In contrast, no gap junctions were found among wall epithelial cells or among dark cells. Fibrocytes and melanocytes were coupled by gap junctions and belong to the connective tissue cell gap junction system, which is continuous throughout the vestibular system and the cochlea. The possible functional significance of these gap junction systems is discussed.

Animals↗

Metabolism of illudin S, a toxic substance of Lampteromyces japonicus. IV. Urinary excretion of an illudin S metabolite in rat.

1. The urinary excretion of a metabolite of illudin S after oral administration to rat has been studied. 2. From an ethyl acetate extract of urine, metabolite 1, a cyclopropane ring-cleavage compound, was identified by liquid chromatographic-mass spectrometric analysis 3. A hplc method for determination of the metabolite in rat urine was developed with extraction using Sep-Pak C18 cartridge followed by liquid-liquid extraction. 4. The metabolite excreted during 3 days after administration of illudin S to rat amounted to approximately 10-19% of the dose as free form and 3-5% of the dose as glucuronide.

Agaricales↗

Amino acid supplementation to hyperalimentation in uremic rats: effects of amount and composition of amino acids on nutrition and uremia.

We evaluated amount and composition of amino acids in supplementation of hyperalimentation from the standpoint of whether it may improve nutrition and/or reduce the indexes of uremia such as BUN. Rats with established uremia, by 5/6 nephrectomy, were treated with various isocaloric solutions containing different amount of essential amino acids and histidine (EAA) or standard amino acids (SAA) which were formulated to provide Cal/N ratios of 300, 600, and 900. The BUN was lower and the nutritional index was better in rats infused with EAA compared with those administrated SAA, while severe distortion of plasma amino acid concentration, hyperammonemia, and fatty liver were observed at the Cal/N 300 condition. Rats infused with SAA gained positive nitrogen balance at the condition of Cal/N 300; however, plasma amino acid distortion was still observed. These results indicate that administration of EAA alone for treatment of renal failure needs high-calorie and low-nitrogen conditions such as Cal/N 600 for avoiding complications. Administration of standard amino acid solution is safe and nutritionally effective in the Cal/N 300 condition, but there are a few problems concerning nitrogen availability and plasma amino acid pattern.

Amino Acids↗

[Changes of lymphocyte subpopulation in advanced renal cell carcinoma patients with marked response to alpha-interferon therapy].

At present, no sufficient therapy for advanced renal cell carcinoma is available. Interferon (IFN) therapy has been used to treat renal cell carcinoma, but the efficacy of it is low, with response rate being only about 20%. We experienced two patients with advanced renal cell carcinoma had marked response to IFN-alpha therapy in proximity effect. Using monoclonal anti-bodies of each subset of lymphocytes, the peripheral blood lymphocytes (PBL) in these patients were evaluated by two color flow-cytometry. And these results and clinical course were assessed. The lymphocyte subpopulation that change of clinical course is been similar to in these patients were Tc (CD11b-CD8+), TSI (leu8+ CD4+), ATS/C (CD8+ HLA-DR+) and ATH/SI (CD4+ HLA-DR+). And the pretherapeutic immunological status of these patients was characterized by significantly increased CD4+/CD8+ and TH/TS ratio. In conclusion, the clinical response of advanced renal cell carcinoma to IFN therapy might be found if CD4+/CD8+ and TH/TS ratio are increased at pretherapeutic immunological status. In addition, assessment of TSI, TC, ATH/SI, and ATS/C, as immune parameters for monitoring the actual immune status of patient is found to be necessary part of immunotherapy.

Adult↗

[The expression of granulocyte colony-stimulating factor in malignant gliomas].

In this study, we investigated the expression of granulocyte colony-stimulating factor (G-CSF), G-CSF mRNA, G-CSF receptor mRNA in glioma cell lines, G-CSF in glioma cyst fluids, and the effect of recombinant G-CSF on the proliferation of glioma cells. First, to determine whether G-CSF is produced by glioma cells, we analyzed for the presence of G-CSF by ELISA in supernatants from glioma cell lines. G-CSF was detected in six of fourteen glioma cell lines constitutively, and, after stimulation with tumor necrosis factor-alpha (TNF-alpha), G-CSF was detected in four of eight cell lines which did not produce G-CSF constitutively. Then, we analyzed the expression of G-CSF mRNA by reverse-transcriptase polymerase chain reaction (RT-PCR) in six cell line, of which two produced G-CSF constitutively and three produced G-CSF only after stimulation with TNF-alpha. G-CSF mRNA was detected in all cell lines studied. To determine whether G-CSF was produced in vivo, we analyzed the presence of G-CSF by ELISA in five glioma cyst fluids, but G-CSF was not detected in any. We also analyzed the effect of G-CSF on the proliferation of glioma cells. The growth of glioma cells alone was not different from that of glioma cells incubated with recombinant G-CSF. In addition, we analyzed the presence of G-CSF receptor mRNA in glioma cells by RT-PCR; G-CSF receptor mRNA was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗

[Transcriptional regulation in airway epithelial cell gene expression].

Analysis of molecular mechanisms that regulate transcription in airway epithelial cells is important not only in understanding the principles of development and differentiation of the airway but also in unravelling the function of proteins encoded in the genes analysed. In addition, a well-characterized promoter of a gene can be used as to regulate the expression of a gene or genes introduced into the airway for gene therapy. For these reasons, we studied the cell-specific transcription of the secretory leukoprotease inhibitor gene and found a cis-element specific to airway epithelial cells in the promoter of this gene.

Amino Acid Sequence↗

[Home chemotherapy for peritoneal carcinomatosis].

Nineteen patients diagnosed with peritoneal carcinomatosis were treated by in-home chemotherapy over a period of four years from August, 1990 to July, 1994. Primary diagnoses of the four male and 15 female patients included 12 cases gastric cancer (four males, eight females), five cases of ovarian cancer, one case (female) of appendicular cancer, and one case (female) of breast cancer. In addition to oral administration of UFT-E and 5'-DFUR, chemotherapy included weekly intravenous injection of a massive dose of 5-FU (1,000 mg/m2), subselective intraaortic infusion and intraperitoneal infusion using a reservoir. These methods were used individually and in combination. The drugs used included 5-FU, CBDCA, CPA, THP, and EPIR. Subselective intraaortic infusion was performed by low dose continuous infusion using the Baxter infusor multiday type. Six gastric cancer patients lived normally for over one year, while four died in less than a year. All ovarian and appendicular cancer patients were CR, the breast cancer patient was PR. Ten patients continued working at their jobs while receiving at home chemotherapy treatments. Diuretics were used to alleviats ascites. Although there were no side effects on digestive organs, 5-FU and CBDCA were mixed with 100 mg hydrocortisone in the infusor to improve cachexia, and promote appetite and activity. Bone marrow suppression was very slight at these dosages, and weekly checkups were adequate. The at-home rate (number of days at home/entire period since onset) of all patients was 78%.

Adult↗

[Valvulo-annuloplasty for atrioventricular valvular regurgitation in univentricular heart and double outlet right ventricle].

Valvulo-annuloplasty for atrioventricular (AV) valvular regurgitation was performed in 10 patients with univentricular heart and double outlet right ventricle. Kay annuloplasty alone was employed in three patients with a quadricuspid or tricuspid common AV valve. Two of them died after the operation and the remaining one is waiting for reoperation because of recurrence of severe AV valve regurgitation. The suturing-up of free margins of the anterior and posterior common leaflets was performed in 3 children with quadricuspid common AV valve and effectively reduced the regurgitation. The semicircular annuloplasty with a thin Gore-tex graft or the suturing-up of floppy leaflets combined with plasty of the chordae and papillary muscle was carried out in two patients having tricuspid AV valve, and a favourable result was obtained in the semicircular annuloplasty. In mitral AV valvular regurgitation, two patients received the suturing-up of free margins of prolapsed leaflets, and the results were satisfactory. From these results we consider that the semicircular annuloplasty for dilated tricuspid AV valve and the suturing-up of free margins of dilated or floppy leaflets in quadricuspid and bicuspid AV valves are the recommendable procedures. If more than mild AV valvular regurgitation remains after these valvuloplasties, the Kay and/or DeVega annuloplasties should be added for eliminating the regurgitation.

Adolescent↗

[Analysis of glucose metabolism in patients with esophageal cancer by PET: estimation of hexokinase activity in the tumor and usefulness for clinical assessment using 18F-fluorodeoxyglucose].

We evaluated glucose metabolism of esophageal cancer by PET using 18F-fluorodeoxyglucose (FDG), in order to investigate its clinical usefulness. In 11 advanced cases k3 value reflecting hexokinase activity and Ci/Cp ratio expressing FDG uptake were calculated from radioactivity in the tumor (Ci) and the plasma (Cp). Both k3 and Ci/Cp were well correlated with hexokinase activity from the resected specimen, so Ci/Cp was considered to be a convenient index for clinical assessment of esophageal cancer. Forty-two cases before treatment revealed high accumulation of FDG, and 41 showed more than 2.0 of Ci/Cp. But, 10 normal controls and one esophageal benign tumor showed less than 2.0. As for 13 post-operative cases, 6 cases out of 7 with recurrence showed more than 2.0 for Ci/Cp, but all 6 cases of non-recurrent cases showed less than 2.0. FDG PET is an useful tool for differential diagnosis of recurrence. The clinicopathological findings were investigated in 26 resected cases. Age, location, vertical extension, histologic feature, lymph node metastasis and histologic stage were not correlative with Ci/Cp. As for DNA ploidy pattern, aneuploidy group showed significantly high Ci/Cp rather than diploidy group. Eight cases which showed more than 5.0 of Ci/Cp resulted in poor prognoses compared with 14 cases which showed less than 5.0.

Aged↗

[Clinical study of continuous warm blood cardioplegia with normothermic cardiopulmonary bypass in coronary artery bypass surgery].

This study was undertaken to determine whether continuous warm blood cardioplegia (CWBCP) could be acceptable as an alternative method for myocardial preservation in cardiac surgery. Between December 1991 and June 1993, 100 consecutive patients underwent coronary artery bypass surgery. Four patients who received terminal warm blood cardioplegia were excluded in this study. Fourty-eight patients (Group C) served as historical controls, and fourty-eight patients (Group W) from October 1992 to June 1993 served as a prospective, consecutive cohort for statistical comparison. Two groups varied in the types of myocardial protection and cardiopulmonary bypass (CPB) used: intermittent cold blood cardioplegia and moderate hypothermic CPB were used in Group C and CWBCP and normothermic CPB in Group W. The groups had similar number of bypass grafting, aortic cross-clamping time and CPB time. No patients was died. The prevalence of intraoperative cerebral infarction was equal in both groups (4.2%). The incidence of spontaneous defibrillation at cross-clamp removal was higher in Group W (85.4% versus 8.3%; p < 0.01). Less inotrope (dopamine) at 6 hours after operation was required in Group W (3.27 +/- 2.48 versus 4.78 +/- 2.99 micrograms/kg/min; p < 0.01). The intraoperative urgent use of the intraaortic balloon pump was noticeably less prevalent in Group W (0% versus 12.5%; p < 0.05). Group W patients were more likely to be hemodynamically stable after CPB discontinuing. Serum potassium levels during CPB was higher in Group W (max. 5.67 +/- 0.96 versus 4.39 +/- 0.50 mEq/l), so excessive potassium was eliminated using extracorporeal ultrafiltration. The major drawback of CWBCP was that continuous coronary perfusate occasionally obscured anastomosis site.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Overexpression of p53 protein in gliomas].

We analyzed the levels of p53 protein in 10 frozen astrocytoma specimens by using an ELISA kit. p53 protein was detected in seven of ten specimens, and ranged from 0.4 to 18.0ng/ml. To confirm that the p53 protein detected in this study actually represented mutations occurring within the p53 gene, we determined the nucleotide sequence in five of six positive cases, and in three of four negative cases. We amplified exons 5 to 9 by the PCR and sequence analysis was carried out by the dideoxy chain termination method. Point mutations resulting in amino acid substitutions were found in four of five positive cases but not in negative cases. Then we analyzed the presence of p53 protein in sera of 42 patients with malignant astrocytoma and 34 healthy donors, by the same method. p53 protein was detected in sera of 7 of 42 patients and 6 of 34 healthy donors, suggesting that this result may be due to non-specific responses. In conclusion, using the ELISA kit, overexpression of p53 protein, resulting from p53 mutations, in frozen astrocytoma specimens can be detected. This may be a good screening method for the detection of overexpression of p53 protein.

Astrocytoma↗

Effects of high-molecular-weight sodium hyaluronate on experimental osteoarthrosis induced by the resection of rabbit anterior cruciate ligament.

Sodium hyaluronate (HA) with a molecular weight of 202 x 10(4) (HA-202) was administered into the right knees of mature rabbits for the treatment of experimental osteoarthrosis induced by resection of the anterior cruciate ligament. At six and 12 weeks after the initiation of administration, the test group was compared with a group administered physiological saline solution to determine the effects on articular cartilage and synovial tissue. In both the six- and the 12-week period, cartilage degeneration proceeded with the lapse of time in both groups; however at 12 weeks, the efficacy of HA-202 in inhibiting degeneration was clearly observed at the lateral condyle of the femur and tibia where relatively marked degeneration was observed in the saline group. A comparison was also made among three groups administered HA-95 (sodium hyaluronate with a molecular weight of 95 x 10(4)), HA-202, and saline, respectively, for 12 weeks. The saline group showed the greatest cartilage degeneration accompanied by complete disorganization of the cartilage layer and the disappearance of chondrocytes. The degeneration was less in the HA groups, and it was more significantly inhibited in the HA-202 group than in the HA-95 group.

Animals↗

Effect of high-molecular-weight sodium hyaluronate on immobilized rabbit knee.

Experimental osteoarthrosis of the knee joint was induced in rabbits using a polyethylene binding brace. A 1% solution of sodium hyaluronate (HA) of molecular weight 1.73 x 10(6) (HA-173) was administered intraarticularly at a dosage of 0.1 ml/kg body weight twice a week. Changes in articular cartilage and synovial membrane, and joint contracture were compared with a saline control group at intervals throughout a six-week period of immobilization. In all groups, articular cartilage degeneration and joint contracture progressed with time but were inhibited by the administration of HA-173. Additionally, the results of a 1% solution of HA of molecular weight 9.8 x 10(5) (HA-98), a 1% solution of HA of molecular weight 2.02 x 10(6) (HA-202), and saline, each administered twice a week for five weeks at a dose of 0.1 ml/kg body weight, were compared. It was clear that the articular cartilage degeneration was significantly inhibited by HA as compared with saline, and that the effect was more potent with the higher molecular weight, HA-202, than with HA-98. Furthermore, joint contracture was inhibited by HA, and the effect was more potent with the higher molecular weight, HA-202, than with HA-98.

Animals↗

[Three siblings of painful muscle cramps (generalized muscle cramp disease) with alopecia and endocrinological disorders].

Three siblings with generalized painful muscle cramps, generalized alopecia, and endocrinological abnormalities are presented. Their clinical features are very similar to those in sporadic cases reported as having generalized muscle cramp disease. Autosomal recessive inheritance was suggested in our patients. Abnormal laboratory tests include hypersecretion of insulin after glucose loading, elevated levels of luteinizing hormone (LH) and follicular stimulating hormone (FSH), and hypersecretion of LH in the LH-RH test. An elevation of IgG and IgG index in the cerebrospinal fluid (CSF) of two patients suggests IgG production in the CSF. Oral administration of 75 to 150 mg of dantrolene sodium decreased the frequency, intensity, and duration of cramps in all cases. Autoimmune mechanisms based upon hereditary abnormalities are suggested as a cause of their disease.

Adult↗

Endothelin-1 analogues substituted at both position 18 and 19: highly potent endothelin antagonists with no selectivity for either receptor subtype ETA or ETB.

Novel endothelin-1 (ET-1) analogues which are highly potent endothelin antagonists at both receptor subtype ETA and ETB are reported. The replacement of Asp18 with the Thr18 and of Ile19 with a hydrophobic amino acid whose side-chain branches on the gamma-carbon such as Leu, cyclohexylalanine, and gamma-methylleucine (gamma-MeLeu) resulted in loss of or significantly decreased the biological activity of ET-1, while high affinity for the ETA (IC50 = 0.42-0.70 nM) and ETB (IC50 = 0.17-0.43 nM) receptor was retained. These compounds were shown to have high antagonist activities in ET-1-induced vasoconstriction of porcine coronary artery (pA2 7.4-7.7) and in Sarafotoxin S6c-induced vasoconstriction of rabbit pulmonary artery ([Thr18, gamma-MeLeu19]ET-1: pA2 8.4). Among these compounds, [Thr18, gamma-MeLeu19]ET-1 has the desirable characteristic of possessing no agonist activity at either receptor subtype.

Amino Acid Sequence↗

The sequence of the mouse phosducin-encoding gene and its 5'-flanking region.

Phosducin (Pd), a principal protein of retinal photoreceptor cells, modulates the phototransduction cascade by interacting with transducin. A recent report indicated that Pd and the G-protein-inhibitor protein (GIP) in brain are virtually identical. Here, we have sequenced the complete mouse clone (P1-AT) carrying the Pd gene, 3026 bp of its 5'-flanking region, and cDNAs generated from the retinal mRNAs. Gene Pd is 15 kb in length and has four exons. The splice sites for donor and acceptor were in good agreement with the GT/AG rule. Deduced Pd amino acid sequences were highly homologous to those of human, bovine and rat. In addition, we found more than one similar Pd gene and two different mRNAs. The P1-AT clone encodes one of the Pd mRNAs. These results open the possibility that the multiple Pd genes encode multiple Pd.

Animals↗

Antitumor effect of 22-oxa-calcitriol, a noncalcemic analogue of calcitriol, in athymic mice implanted with human breast carcinoma and its synergism with tamoxifen.

The antitumor effect of 22-oxa-calcitriol (OCT), a newly developed noncalcemic analogue of calcitriol, was examined in vivo in athymic mice implanted with human breast carcinoma with or without estrogen receptor (ER). In ER-positive MCF-7 tumor, the growth of which was dependent on exogenous estrogen, administration p.o. of OCT as well as the antiestrogen tamoxifen five times a week for 4 weeks suppressed tumor growth in a dose-related fashion. The antitumor effect of 1.0 microgram/kg body weight (BW) OCT (mean +/- SEM of tumor weight in 6 mice: 28 +/- 4% of vehicle-treated group) was comparable to that of 2.0 mg/kg BW tamoxifen (25 +/- 6% of control group). In addition, a synergistic antitumor effect of submaximal doses of OCT and tamoxifen was observed in MCF-7 tumor in vivo as well as in ER-positive breast carcinoma cell lines (MCF-7 and ZR-75-1) in vitro. Administration of OCT p.o. three times a week for 4 weeks also suppressed the growth of ER-negative MX-1 tumor in a dose-dependent manner without raising serum calcium concentrations. The antitumor effect of 1.0 microgram/kg BW OCT (mean +/- SEM of tumor weight in 10 mice: 44 +/- 6% of vehicle-treated group) was greater than that of 500 micrograms/kg BW Adriamycin (71 +/- 6% of control group). These results indicate that OCT suppresses the growth of ER-negative as well as ER-positive breast carcinoma in vivo without causing hypercalcemia and that the antitumor effect of OCT can be enhanced by tamoxifen in an ER-positive tumor. It is suggested that OCT may provide a new strategy, either alone or in combination with other anticancer drugs, for systemic adjuvant therapy of breast carcinoma regardless of ER status.

Animals↗