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Biomedical subjects

T Takeuchi

Publications and source records attributed to T Takeuchi.

At least 91 records · Page 5Linked to original sources
PubMed1994

Intra-arterial chemotherapy using a reservoir for endocrine-refractory prostate cancer.

For local control in patients with endocrine-refractory prostate cancer, an intra-arterial chemotherapy regimen comprising methotrexate (MTX), Adriamycin (ADM), and cisplatin (CDDP) was evaluated. A total of 19 patients having a mean age of 66.4 +/- 8.8 years and a mean performance status (PS) of 1.3 +/- 1.0 were enrolled. Of these patients, 3 had proved to be resistant to initial endocrine therapy and the remaining 16 had relapsed from disease stabilization after endocrine therapy. The catheter tip was placed in the internal iliac artery in 16 cases, in the common iliac artery in 2 cases, and in the aorta in 1 case after occlusion of the contralateral feeding artery. The intraarterial chemotherapy was performed mainly using MTX (30 mg/m2), ADM (30 mg/m2), and CDDP (50 mg/m2) as one course and was repeated for a mean of 2.9 +/- 2.3 courses. Then, in an outpatient clinic, 5-fluorouracil (5-FU), ADM, or MTX was given intra-arterially as maintenance chemotherapy until re-relapse. As based on the criteria for evaluation of nonsurgical therapy in prostate cancer proposed by the Japanese Urological Association, the prostatic lesion showed a partial response (PR) in 9 cases and no change (NC) in 10 cases. As judged from the response of prostate-specific antigen (PSA), a complete response (CR) was obtained in 6 cases, a PR, in 3 cases; and NC and progressive disease (PD), in 2 cases each. Therefore, the overall response rate was 63%. Improvement in the symptoms was observed in 83% of patients. The duration of the response was 15.1 +/- 10.5 months for the PR cases and 7.4 +/- 5.7 months for the NC cases. Furthermore, the mean survival time observed in the PR group was 38.9 months, which was better than that seen in the NC (16.4 months) and PD (10.5 months) groups. These results suggest that intra-arterial chemotherapy may become an option for the treatment of locally advanced and endocrine-refractory prostate cancers. Using a reservoir, this chemotherapy can be easily given in an outpatient clinic.

Abdominal Muscles↗
PubMed1994

Expression of human tyrosine hydroxylase-chloramphenicol acetyltransferase (CAT) fusion gene in the brains of transgenic mice as examined by CAT immunocytochemistry.

We have produced transgenic (Tg) mice carrying 5.0-kb fragment from the 5'-flanking region of the human tyrosine hydroxylase (hTH) gene fused to a reporter gene, chloramphenicol acetyltransferase (CAT) [Sasaoka et al. (1992) Mol Brain Res 16: 274-286]. In the brain of the Tg mice, CAT expression has been observed in catecholaminergic (CAnergic) neurons and also in non-CAnergic neurons. The aim of the present study is to examine in detail the cell-type specific expression of the hTH-CAT fusion gene in the brain of the Tg mice, by use of immunohistochemistry for CAT, TH, and aromatic L-amino acid decarboxylase (AADC). CAT-immunoreactive cells were found in CAnergic brain regions which contained TH-positive cells, and also in non-CAnergic brain regions which contained no TH-labeled cells. The non-CAnergic brain regions that represented CAT-stained cells were further divided into two groups: (i) regions containing AADC-labeled cells, for example, bed nucleus of the stria terminalis, nucleus suprachiasmaticus, mammillary body, nucleus raphe dorsalis, inferior colliculus, and nucleus parabrachialis, and (ii) regions containing no AADC-positive cells, for example, main olfactory bulb (except A16), accessory olfactory bulb, nucleus olfactorius anterior, caudoputamen, septum, nucleus accumbens, hippocampus, medial nucleus of the amygdala, entorhinal cortex, nucleus supraopticus, and parasubiculum. The results indicate that the 5.0-kb DNA fragment flanking the 5' end of the hTH gene may contain the element(s) specific for neuron-specific TH expression but which may be insufficient to attenuate ectopic expression.

Animals↗
PubMed1994

Mechanism of transient mental nerve paraesthesia in sagittal split mandibular ramus osteotomy.

We investigated the mechanism involved in paraesthesia associated with sagittal split mandibular ramus osteotomy by three-dimensional computed tomography (3-D CT). Ten female patients underwent this procedure between 1988 and 1991. The inferior alveolar neuro-vascular bundles remained intact during the sagittal osteotomy in all cases. We examined the changes in the shape of the foramen mandibulae over a period of 6 months during which the transient mental nerve paraesthesia was recovered, and studied the distance from the foramen mandibulae to the spina mentalis (F-S distance) as measured on 3-D film. The postoperative 3-D CT scan showed bone resorption in front of the foramen mandibulae, and the F-S distance was shortened by an average of 2.94 mm. These findings suggest that possible causes of the paraesthesia is due to compression of the nerve trunk resulting from posterior movement of the mandibular ramus.

Adolescent↗
PubMed1994

Postnatal reference growth curves for very low birth weight infants.

To construct standard growth curves for Japanese infants of very low birth weight (VLBW) with birth weights of 500-1499 g, we reviewed longitudinal data provided by 54 neonatal intensive care units in Japan. A total of 382 surviving singleton infants, appropriate for gestational age infants, and who were free of neurological sequelae at more than 2.5 years of age, were enrolled. Growth curves, including body weight, head circumference and body length were generated for four ranges of birth weight: 500-749 g, 750-999 g, 1000-1249 g, and 1250-1499 g. When compared with previously published growth data from western countries, Japanese infants of VLBW showed greater weight loss, regained birth weight more slowly, and exhibited smaller average gains in weight, head circumference, and body length. The growth curves reported in western countries may not be useful as reference standards of early postnatal growth in Japan. The new growth curves are a more accurate reflection of current in-hospital growth trends in Japan.

Asian People↗
PubMed1994

Dysgenesis of melanocytes and cochlear dysfunction in mutant microphthalmia (mi) mice.

In order to evaluate the cytological homology of intermediate cells and melanocytes, and to investigate the function of melanocytes in the inner ear, hearing acuity and cochlear pathology were studied in three strains of mice, namely, wild type mice (+/+), albino mice without melanin (c2J/c2J), and microphthalmia mice with no melanocytes (mibw/mibw). Our histochemical data indicated that intermediate cells showed cytological characteristics almost identical to those of melanocytes and that disorders of melanin and/or melanocytes were reflected in the stria vascularis of each mouse. While c2J/c2J presented the same normal hearing acuity and normal structure of the stria vascularis as +/+, the hearing acuity of mibw/mibw mutants was severely impaired. Their stria vascularis was abnormally thin, lacking intermediate cells. According to these results, lack of melanin has little influence on hearing acuity; however, the absence of intermediate cells or melanocytes causes severe hearing loss, presumably due to a strial dysfunction.

Animals↗
PubMed1994

Crocidolite asbestos increased 8-hydroxydeoxyguanosine levels in cellular DNA of a human promyelocytic leukemia cell line, HL60.

Crocidolite, one of the most carcinogenic asbestos fibers, induces the release of reactive oxygen species (ROS) from neutrophils and macrophages. Using HPLC combined with electrochemical detection, we determined that 8-hydroxydeoxyguanosine (8OHdG), a molecule typical of mutagenic oxidative DNA damage, was induced in the cellular DNA of a human promyelocytic leukemia cell line, HL60, incubated with crocidolite. Crocidolite increased 8OHdG in the cellular DNA of phorbol myristate acetate (PMA)-differentiated HL60, which phagocytosed crocidolite. PMA-differentiated HL60 released ROS spontaneously, as determined by ESR with 5,5-dimethylpyrrolone-N-oxide as a spin trap. However, the release of ROS from the cell line did not increase after the addition of crocidolite. The addition of superoxide dismutase at a sufficient concentration to scavenge ROS released from the cell did not inhibit the 8OHdG increase induced by crocidolite. Cytochalasin B, which inhibited phagocytosis, did not inhibit the release of ROS. However, it inhibited the crocidolite-induced 8OHdG increase by 48.3%. Contrary to PMA-differentiated HL60, undifferentiated HL60 neither phagocytosed crocidolite nor showed a crocidolite-induced increase in 8OHdG formation. The 8OHdG increase induced by crocidolite was not correlated with ROS release, but with the internalization of crocidolite, suggesting that the increase was not due to an increase in ROS release from the cell but was due to the conversion of relatively inert ROS to highly reactive ROS, such as hydroxyl radicals, by crocidolite that was internalized and close to DNA.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

Evaluation of 8-hydroxydeoxyguanosine, a typical oxidative DNA damage, in human leukocytes.

8-Hydroxydeoxyguanosine (8-OHdG) is a typical form of oxidative DNA damage which causes mutation in vitro and in vivo. We investigated potential factors confounding 8-OHdG determination and, based on the results, then determined the 8-OHdG levels in human peripheral blood leukocytes. 8-OHdG was detected electrochemically after extraction of DNA from the cells without the use of phenol by a DNA extractor under helium. In the preliminary experiments, the mononuclear leukocytes (MN) in blood samples obtained from 19 laboratory workers and students were separated from the polymorphonuclear leukocytes (PMN) with Mono-Poly resolving medium. The 8-OHdG in the MN (1.157 +/- 0.414 molecules per 10(5) deoxyguanosine) did not differ significantly from that in PMN (1.131 +/- 0.418). The effect of red blood cells (RBC) on 8-OHdG formation during DNA extraction was then examined by adding RBC to the human lymphoblastoid cell line FA72. Addition of RBC at ratios of up to 4 RBC per FA72 cell did not increase 8-OHdG levels, while addition at a RBC/FA72 cell ratio of 20 increased the 8-OHdG level 1.43-fold over that without RBC. The potential effect of histidine, a scavenger of both hydroxyl radicals and singlet oxygen, on reduction of artificial 8-OHdG formation during DNA extraction was examined during DNA extraction in the human promyelocytic leukemia cell line HL60. Addition of His decreased the 8-OHdG level dose-dependently (30% reduction at 30 mM His concentration). Based on these results, we determined the 8-OHdG levels in human leukocyte samples obtained from 79 healthy male factory workers aged 24-59 years. The leukocyte fraction containing both MN and PMN was separated from RBC with Mono-Poly resolving medium and DNA was extracted from the leukocytes in the presence of 30 mM His. The mean 8-OHdG level in these samples was 1.072 +/- 0.230. To evaluate the reliability of the assay, FA72 was used as a standard sample in all assay determinations and the 8-OHdG levels of both the leukocyte samples and the FA72 sample(s) were measured in each determination. The inter- and intra-assay coefficients of variation (CV) were calculated to be 14.4% (n = 14) and 3.9-13.5% (n = 3-5 per assay) respectively. The 8-OHdG level was measured twice in 19 leukocyte samples; the value at the first determination was not correlated with that at the second determination. The range of 8-OHdG levels in the samples was relatively small compared with the CV of the assay.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1994

A new CCK-A antagonist, KSG-504, administered intraduodenally, inhibits pancreatic secretion in rats.

We studied the effect in anesthetized rats of a new cholecystokinin (CCK) receptor antagonist developed in Japan, KSG-504, administered intraduodenally, on pancreatic exocrine secretion stimulated by exogenous CCK and intraduodenal casein. Intraduodenal administration of KSG-504 in graded doses of 2.5-50 mg/kg/h produced dose-dependent inhibition of pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 micrograms/kg/h. The ID50 (half-maximal inhibition dose) of KSG-504 for CCK-8-stimulated amylase secretion was 3.4 mg/kg/h. Moreover, intraduodenal KSG-504 (5 and 25 mg/kg/h) dose dependently suppressed pancreatic juice volume, and amylase output increased with intraduodenal infusion of casein (400 mg/h). It is concluded that KSG-504 administered intraduodenally has a significant, potent inhibitory action on the exocrine pancreas stimulated by exogenous CCK and intraduodenal casein.

Animals↗
PubMed1994

CA19-9 as a screening and diagnostic tool in symptomatic patients: the Japanese experience.

Although the prognosis for pancreatic cancer is generally poor, the Japanese Pancreatic Cancer Register reported in 1992 that the survival rate for resected pancreatic cancer was much higher than that for more conservative treatment. T1 and T2 pancreatic tumors are much more frequently resectable than are T3 and T4 tumors, and the 5-year survival rate for unresected T2, T3, and T4 cases is 0%. These findings emphasize the importance of early diagnosis of resectable pancreatic cancer. CA19-9 has shown satisfactory sensitivity in detecting advanced pancreatic cancer; we sought to determine the effectiveness of CA19-9 as part of a screening program for early cancer. Using elastase 1, CA19-9, and ultrasonography, we developed and tested a program of mass screening on persons presenting with and without abdominal complaints.

Adult↗
PubMed1994

Comparison of CA19-9 with other tumor markers in the diagnosis of cancer of the pancreas.

The carbohydrate antigen 19-9 (CA19-9) and radioimmunoassay have been shown to offer new hope for improving the diagnosis of pancreatic cancer, and various tumor markers (including SPan-1, DUPAN-2, and CA50) have been established. While clinical studies of these markers have found satisfactory sensitivities, only a few studies have compared these tumor markers on the same blood samples. We therefore evaluated the clinical efficacy of SPan-1, CA19-9, DUPAN-2, CA50, carcino-embryonic antigen, and Elastase 1 in detecting pancreatic cancer in identical blood samples.

Antigens, Neoplasm↗
PubMed1994

A novel mutation in the erythrocyte protein 4.2 gene of Japanese patients with hereditary spherocytosis (protein 4.2 Fukuoka).

Human erythrocyte protein 4.2 (band 4.2; pallidin) is a major membrane protein that comprises 5% of the total weight of the human erythrocyte membrane. Deficiencies of this protein have been observed in hereditary spherocytosis with anaemia, suggesting a role of protein 4.2 in erythrocyte stability and integrity. The molecular basis of this disorder remains unknown. As a first step in elucidating the pathogenesis of hereditary spherocytosis associated with protein 4.2 deficiency, we cloned and sequenced the erythrocyte protein 4.2 gene from a normal Japanese person. We prepared sets of oligonucleotide primers for polymerase chain reaction (PCR) and determined nucleotide sequences of exons and exon-intron boundaries of the protein 4.2 gene from three unrelated Japanese patients with hereditary spherocytosis due to a complete defect of protein 4.2, using PCR-related techniques. Two patients were homozygous for a missense mutation in codon 142 with the Ala (GCT)-->Thr (ACT) amino acid substitution that has been reported previously (protein 4.2NIPPON), whereas one patient was compound heterozygous for the same missense mutation in codon 142 and a guanine-adenine transition in codon 119 that changes the codon for Trp (TGG) to the termination codon (TGA) (protein 4.2Fukuoka). No additional mutation was identified in other exons of the protein 4.2 genes. Dot-blot hybridization with allele-specific oligonucleotide probes showed that homozygosity for the missense mutation in codon 142 and compound heterozygosity for the codon 142 and the codon 119 mutations were related to protein 4.2 deficiency in the families. Although two alleles of missense mutation of the codon 142 were also detected in 100 alleles of healthy Japanese, results obtained in this study indicate that the two mutations described above are closely related to the pathogenesis of hereditary spherocytosis due to protein 4.2 defect.

Adult↗
PubMed1994

Improvement of mitomycin C- and cyclophosphamide-induced thrombocytopenia and leucocytopenia by prior treatment with deoxyspergualin in dogs.

Deoxyspergualin (DGS) is a new immunosuppressant which has shown inhibitory haemopoietic activity. We investigated the myeloprotective effect of DSG against the haemopoietic injury of mitomycin C (MMC) or cyclophosphamide (CYC) by measuring peripheral blood cell numbers in dogs. DSG given at 5 mg/kg on days 3, 2 and 1 before, or at 10 mg/kg on either days 2 and 1 before or on day 1 before and the day of injection of MMC at 0.25 mg/kg ameliorated both the thrombocytopenia and leucopenia caused by MMC. This ameliorative effect was more evident on platelet counts than on white blood cell counts. In addition, the leucopenia and thrombocytopenia induced by a single injection of CYC at 10 mg/kg was also ameliorated by prior DSG administration. These findings suggest that DSG may be useful in protecting against the haemopoietic damage induced by chemotherapeutic agents in the treatment of cancer.

Animals↗
PubMed1994

Cellular composition of the pancreatic islets in Mongolian gerbils (Meriones unguiculatus).

In Mongolian gerbil, morphological changes with age in the content of endocrine cells in the pancreatic islets were analyzed and their relation evaluated by an oral glucose tolerance test. The glucose level 2 hours after glucose administration was 125 +/- 5 mg./d1 in the young group and 103 +/- 4 mg./d1 in the old group. In the dorsal portion, B cells were mainly observed in the central area of the islets, surrounded by circular layers of A cells in the peripheral area. Between the A cells and B cells, D cells were scattered or present in layers. A few PP cells were present in the peripheral area of the islets. In the ventral portion, only a few A cells were observed in the peripheral area of the islets, and B cells were surrounded by PP cells. Secretory granules of A cells generally had an electron-dense spherical core in the limiting membrane. The halo between the limiting membrane and core in A cells was narrower than that in B cells. Secretory granules of B cells were larger than those in A cells, and the core was less electron-dense, and the halo was wider. Secretory granules of D cells were similar in size to those of A cells; the core showed low electron density, and the halo was very narrow. Granules of PP cells resembled those of A cells, but the electron density of the core was slightly lower. The gerbils showed changes in glucose tolerance, the size of the pancreatic islets, the percentage of B cells, and of A cells in the dorsal portion with age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1994

Efficacy of synchronized IMV on weaning neonates from the ventilator.

This study evaluated the efficacy of a new patient-triggered ventilator that triggered the patient's inspiratory effort by detecting the change in airflow by means of a 'hot wire' anemometer. This ventilator was used in both the conventional and the synchronized intermittent mandatory ventilation (SIMV) modes in seven neonates. Values for blood gas, spontaneous breathing rate, tidal volume of spontaneous breaths and minute volume were compared in all seven neonates. The resistive work of spontaneous breathing in five neonates, obtained with synchronized intermittent mandatory ventilation was compared with the values obtained using conventional mechanical ventilation on the previous day of weaning from the ventilator. At each the inflation time studied (0.4, 0.3, 0.24 s), all mechanical breath occurred synchronously with infants' inspiratory efforts. The median trigger delay was 80 ms. Oxygenation was improved on the new system compared with the conventional system. Tidal volume of spontaneous breathing and minute volume were increased with SIMV compared with conventional mechanical ventilation, although the resistive work of spontaneous breathing was decreased with SIMV. The tidal volume of spontaneous breaths was more constant with SIMV versus conventional mechanical ventilation. Thus, the airway flow-triggered SIMV may lessen inspiratory muscle fatigue during weaning process. We conclude that the SIMV is useful in weaning neonates from the ventilator.

Equipment Design↗
PubMed1994

Nitric oxide-mediated inhibitory response of rat proximal colon: independence from changes in membrane potential.

1. We studied the relation of nitric oxide-mediated relaxation of smooth muscle to changes in membrane potential of cells in the proximal colon of rats. 2. The resting membrane potential and electrical field stimulation (EFS)-induced junction potentials were recorded from the circular and longitudinal muscle cells. 3. Localized distension with a small balloon caused relaxation of the circular muscle on the anal side of the distended region (descending relaxation). Relaxation of the longitudinal muscle was also induced by EFS. 4. Inhibitory junction potentials (i.j.ps) were recorded from all circular muscle cells tested, but rarely from the longitudinal muscle cells. 5. The i.j.ps were recorded only in the presence of atropine but relaxations of both muscles were induced even in the absence of atropine. 6. Apamin (100 nM) completely abolished the i.j.ps recorded in both circular and longitudinal muscle cells, but had no significant effect on the relaxations of either. 7. In contrast to apamin, Ng nitro-L-arginine (10 microM) inhibited the relaxations of both muscles, but did not affect the i.j.ps. 8. Exogenously added nitric oxide (0.1-10 microM) induced relaxations of both muscles concentration-dependently, but did not affect the membrane potentials at these concentrations. 9. These data strongly suggest that nitric oxide-mediated relaxation of rat proximal colon is not associated with the i.j.ps of the cell membrane.

Animals↗
PubMed1994

Identification of nuclear factors that bind to the mouse tyrosinase gene regulatory region.

Several nuclear factors that interact with sequences in the 5' flanking region of the mouse tyrosinase gene were identified using band shift and methylation interference assays. One of these factors bind to an AT-rich sequence, TATCAATTAG, located at -183 base pairs upstream of the transcription start site. To isolate cDNA clone encoding this DNA binding protein, we have screened a lambda gt11 cDNA expression library prepared from mouse melanocyte cell line with a labeled oligonucleotide probe containing its binding site. Complementary DNA clones encoding mouse high mobility group protein HMG-I and its isoform HMG-Y were obtained. HMG-I(Y) is a low molecular size, basic nuclear protein that binds specifically to AT-rich region of double-stranded DNA in vitro. In Northern blot analysis the level of HMG-I(Y) mRNA expression did not correlate with that of tyrosinase or TRP-1. Although the amount of HMG-I(Y) transcripts has no apparent influence on the mouse tyrosinase gene expression, it is possible that HMG-I(Y) binds to the 5' flanking sequence of the tyrosinase gene as an auxiliary factor, and facilitates the binding and activity of other transcription factors.

Animals↗