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Biomedical subjects

O Tanaka

Publications and source records attributed to O Tanaka.

At least 73 records · Page 4Linked to original sources
PubMed1996

The abnormal distribution of mossy fiber bundles and morphological abnormalities in hippocampal formation of dreher(J) (dr(J)/dr(J))mouse.

The organization of pyramidal cells and mossy fibers in the hippocampal formation of homozygous dreher(J) mutant mice was investigated using Timm's and Golgi methods. Five clear abnormalities were found: (1) some pyramidal cells were located below the infrapyramidal mossy fiber layer, (2) mossy fibers emerged in diffuse fashion from between the suprapyramidal and infrapyramidal mossy fiber layers, and their fibers invaded within the pyramidal cell layer, where they traveled as 3-6 small, usually quite short, bundles, (3) some normally situated pyramidal cells had unusual contacts with mossy fibers at two or three places on their apical and/or basal dendrites, (4) some normally situated pyramidal cells had abnormal dendritic trees typified by the occurrence of fine-caliber dendritic branches extending out of the apical dendrite or the apical portion of the soma, and (5) a few Timm positive fibers extending from the dentate hilus to the dentate molecular layer in both dreher(J) and control mice were observed. These abnormalities indicate that in the hippocampal formation a variety of cell populations and neuronal circuits can be indirectly modified by the dreher mutation.

Animals↗
PubMed1996

Simultaneous expression of keratan sulphate epitope (a sulphated poly-N-acetyllactosamine) and blood group ABH antigens in papillary carcinomas of the human thyroid gland.

The monoclonal antibody 5-D-4 recognizes heavily sulphated forms of keratan sulphate epitope. It reacted strongly with the cell surfaces of most thyroid papillary carcinomas from all the individuals examined, independently of the blood group of the patients. Cells of follicular variants of papillary carcinomas were also labelled by 5-D-4. In contrast, no labelling with this antibody was observed in other types of thyroid neoplasms, or in normal tissues. The reactivity of 5-D-4 with papillary carcinomas was markedly reduced or abolished by prior digestion with endo-beta-galactosidase, keratanase II, or N-glycosidase F. Although keratanase digestion had no effect on 5-D-4 labelling, it revealed the binding sites of Griffonia simplicifolia agglutinin II (GSA-II), which recognizes terminal N-acetylglucosamine in a limited number of carcinoma cells from some individuals. Blood group ABH antigens, which are simultaneously expressed together with keratan sulphate epitope in cancer cells, were eliminated by digestion with endo-beta-galactosidase and N-glycosidase F, but were resistant to keratanase and keratanase II treatment. These results indicate that keratan sulphate oligosaccharides are cancer-associated and are probably oncofoetal antigens, as are the blood group antigens in human thyroid glands. The results suggests that poly-N-acetyllactosamine, which is ubiquitously and consistently produced in papillary carcinomas, is modified in two different ways: sulphation on the 6-position of at least some units of either galactose or N-acetylglucosamine or both, and decoration of non-reducing termini with the blood group antigens. Along with the endo-beta-galactosidase-GSA-II labelling procedure, labelling with 5-D-4 may be a useful diagnostic means for distinguishing papillary carcinoma from other types of thyroid neoplasms.

ABO Blood-Group System↗
PubMed1996

Possible inhibitory effect of diazepam on the metabolism of zotepine, an antipsychotic drug.

Effects of smoking and cytochrome P450 2C19 (CYP2C19) status on the single dose kinetics of zotepine and pharmacokinetic interaction between zotepine and diazepam were investigated. In 14 healthy volunteers, the pharmacokinetics of zotepine after a single oral 25 mg dose were compared between eight smokers and six non-smokers, or between seven extensive metabolizers (EMs) and seven poor metabolizers (PMs) of S-mephenytoin. There was no significant difference in any pharmacokinetic parameters between smokers and non-smokers, or between the EM and PM groups. In 17 patients treated with zotepine 80-340 mg/day, intra-individual changes in plasma concentrations of zotepine caused by coadministration of diazepam 10 mg/day for 2 weeks were examined. Plasma concentrations of zotepine were significantly increased after coadministration of diazepam (P < 0.05). Consequently, it is suggested that neither smoking nor CYP2C19 status affects the metabolism of zotepine. The elevation in plasma concentrations of zotepine after coadministration of diazepam may be a result of competitive inhibition of zotepine metabolism by diazepam via other isoenzyme than CYP2C19, e.g., CYP3A4.

Adult↗
PubMed1996

Plasma prolactin concentration and psychopathology of schizophrenia.

1. The correlation between plasma prolactin concentration and psychopathology, as assessed by the BPRS, was studied in 56 unmedicated schizophrenic patients (28 males, 28 females). 2. There was no significant correlation between plasma prolactin concentration and total BPRS score or each item score. 3. No significant correlation was found when the BPRS items were classified into five clusters, i.e., positive, excitement, cognitive, negative, and anxiety-depression symptoms. 4. When males and females were analyzed separately, no significant correlation was found except a weak negative correlation (rs = -0.388, p < 0.05) for hostility score in females. 5. The present study suggests that plasma prolactin concentration does not reflect psychopathology of schizophrenia.

Adolescent↗
PubMed1996

Drug sensitivity testing for clinical samples from oesophageal cancer using adhesive tumour cell culture system.

A total of 83 specimens of surgically resected tumours from 78 patients with oesophageal cancer were assayed for drug sensitivity using an adhesive tumour cell culture system (LifeTrac CSA assay). Seventyone of 83 specimens had a sufficient number of cells to permit growth in culture and 57 of 71 (80%) were evaluable for drug response. Cells (3 x 10(3) ml-1 well-1) were cultured for 14 days and exposed to drugs on days 3-8. Growing cells were confirmed as cancer cells by immunohistochemical staining. IC90 values against several anti-cancer drugs were determined and population distributions of IC90 for each drug served as the basis for judging sensitivity. The 10th percentiles of IC90 (microgram ml-1) for CDDP, 5-FU, DOX, CPM, MTX, VP16, IFOS, VDS, BLM and CDDP + 5-FU were 0.3, 0.16, 0.005, 0.9, 0.006, 0.09, 0.8, 0.006, 0.04 and 0.15 + 0.09 respectively. The population distribution of IC90 against each drug showed a specific pattern that was very similar among histopathological gradings and stages of the disease. This system appeared to be a clinically applicable drug sensitivity test for human oesophageal cancer.

Antineoplastic Agents↗
PubMed1996

A method for rapid determination of zotepine by gas chromatography-mass spectrometry.

A rapid and sensitive method using solid-phase extraction and gas chromatography-mass spectrometry (GC-MS) has been developed for the determination of zotepine (ZTP), an atypical neuroleptic, in human plasma. The detection limit of ZTP was 1 microgram/L. Standard curves over the concentration range from 2.5 to 100 micrograms/L had a good linearity. Intraassay variability ranged from 2.2 to 3.3% and interassay variability from 3.5 to 6.6% at the concentration range of 5-75 micrograms/L. Our preliminary data of single-dose kinetics of ZTP by using this method suggested that the peak time and elimination half-life was much longer than previously reported, and that there appeared to be a second peak after 10-12 h of ZTP administration, indicating the possibility of the presence of enterohepatic recirculation.

Antipsychotic Agents↗
PubMed1996

Protection against oxidative damage by dihydroflavonols in Engelhardtia chrysolepis.

Dihydroflavonol taxifolin and its glycoside, astilbin, from Engelhardtia chrysolepis were evaluated as antioxidants and radical scavengers. These dihydroflavonols inhibited superoxide anion production in the xanthine/xanthine oxidase system. Microsomal lipid peroxidation induced by NADPH-cytochrome P-450 reductase was also inhibited by these flavonoids. Mitochondrial lipid peroxidation was inhibited only by the aglycon. Taxifolin protected peroxy radical-damaged mitochondria with no effect on enzyme activity. Furthermore, taxifolin and astilbin protected red cells against oxidative hemolysis. These dihydroflavonols were found to be effective for protecting subcellular systems and red blood cells against oxidative stress in vitro.

Animals↗
PubMed1996

The role of magnetic resonance imaging in the diagnosis and monitoring of myelodysplastic syndromes or leukemia.

Magnetic resonance imaging (MRI) can provide valuable information about regions of the bone marrow which are inaccessible to biopsy. MRI also is unique in characterizing normal and abnormal bone marrow because of its ability to distinguish fat from other tissues. In patients with myelodysplastic syndromes (MDS) or leukemia, marrow MRI is an important tool for accurate diagnosis and monitoring and may function as an adjunct to bone marrow aspiration and biopsy. In clinical practice, defining the anatomic distribution and extent of marrow involvement by MRI is of advantage in the management of patients with MDS or leukemia.

Bone Marrow↗
PubMed1996

[MR relaxation times in diffuse bone marrow disorders: evaluation of their clinical usefulness in differentiation between leukemia and anemia].

T1 and T2 relaxation time measurements of the femoral marrow were performed in 20 patients with acute myeloid leukemia (AML) and 9 patients with iron deficiency or other severe anemia who had shown diffuse abnormal signals on MR imaging of the femoral marrow. The ability of T1 and T2 values to differentiate between leukemic infiltration and hyperplastic hematopoietic marrow was evaluated. T1 and T2 ratios (T1 abnormal marrow/T1 normal marrow and T2 abnormal/T2 normal) were calculated, and the ratios of T1 to T2 (T1/T2) and of the T1 ratio to the T2 ratio (T1 ratio/T2 ratio) were also analyzed. Diffuse infiltrative marrows revealed prolonged T1 relaxation times in all patients with AML and other severe anemia, and it was not possible to distinguish the two groups of diseases on the basis of T1 values. The T2 relaxation times varied widely in AML, but the mean T2 value of the AML group was not statistically significantly different from that of the anemia group. There were also no significant differences in the T1 ratio, T2 ratio, T1/T2, and the T1 ratio/T2 ratio between leukemic infiltration and hyperplastic hematopoietic marrow. We concluded that measurement of T1 and T2 relaxation times was of limited clinical importance for the histological characterization of diffuse bone marrow disorders.

Adult↗
PubMed1996

[Pharmacokinetics of zotepine and various factors affecting that of zotepine].

The single dose kinetics of zotepine, and effects of smoking and cytochrome P450 2C19 (CYP2C19) on the kinetics, together with pharmacokinetic interaction between zotepine and diazepam were investigated. 1) The pharmacokinetics of zotepine was investigated in 14 healthy volunteers, and was compared between 7 extensive metabolizers (EM) and 7 poor metabolizers (PM) of CYP2C19 or between 8 smokers (S) and 6 non-smokers (NS). 2) In 17 patients treated with zotepine alone, intraindividual changes in the plasma concentrations of zotepine before and after coadministration of diazepam were examined. The time of the maximal plasma concentration and the elimination half-life of zotepine in 14 volunteers were about 4 hours and 21 hours, respectively, which were found to be much longer than previously reported data. There were no significant differences in the pharmacokinetic parameters between the EM and PM groups or between the S and NS groups. The plasma concentrations of zotepine were significantly increased after coadministration of diazepam. Consequently, it is suggested that smoking does not affect the pharmacokinetics and metabolism of zotepine, and that the metabolism of zotepine is not mediated by CYP2C19. Elevation in the plasma concentrations of zotepine after coadministration of diazepam may be caused by the inhibitory effect of diazepam on zotepine metabolism. As a plausible explanation for this, the metabolism of zotepine and diazepam may be commonly mediated not by CYP2C19 but by cytochrome P450 3A4, and the pharmacokinetic interactions may result from competitive inhibition between these two drugs.

Adult↗
PubMed1996

[MR imaging of the femoral marrow in adult acute leukemia: correlation of MRI patterns with FAB subtype and prognosis].

MR imaging of the femoral marrow was performed in 36 patients with untreated acute myeloid leukemia (AML) and 7 patients with acute lymphocytic leukemia (ALL). The MRI appearance was classified into five patterns: 1) fatty marrow; 2) faint signal; 3) nodular pattern; 4) heterogeneous infiltration; and 5) diffuse infiltration. The MRI patterns of the femoral marrow were compared among the FAB subtypes of acute leukemia, and the MRI patterns were correlated with prognosis. All five MRI patterns were observed in the femoral marrow in adult acute leukemia, and diffuse infiltration was most commonly seen (41.9%). A completely fatty marrow was also depicted in two cases (4.7%) and faint signal in four cases (9.3%) in spite of untreated acute leukemia. The M2 subtype of AML tended to be demonstrated as a minimally abnormal MRI finding, which was significantly different from the other types of AML. The patients who showed fatty marrow or faint signal were thought to have a good prognosis, while diffuse or heterogeneous infiltration was regarded as a poor prognostic sign. However, there were some exceptions to these rules, and no significant differences were revealed in prognosis between minimally abnormal and advanced MRI patterns. We concluded that MRI of the femoral marrow could be useful in the assessment of tumor volume of adult acute leukemia, and that there were limitations to predicting prognosis on the basis of the MRI manifestations.

Acute Disease↗
PubMed1995

Regulatory role of CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase) in insulin secretion by glucose in pancreatic beta cells. Enhanced insulin secretion in CD38-expressing transgenic mice.

Cyclic ADP-ribose (cADPR) serves as a second messenger for Ca2+ mobilization in insulin secretion, and CD38 has both ADP-ribosyl cyclase and cADPR hydrolase activities (Takasawa, S., Tohgo, A., Noguchi, N., Koguma, T., Nata, K., Sugimoto, T., Yonekura, H., and Okamoto, H. (1993) J. Biol. Chem. 268, 26052-26054). Here, we produced transgenic mice overexpressing human CD38 in pancreatic beta cells. The enzymatic activity of CD38 in transgenic islets was greatly increased, and ATP efficiently inhibited the cADPR hydrolase activity. The Ca2+ mobilizing activity of cell extracts from transgenic islets incubated in high glucose was 3-fold higher than that of the control, suggesting that ATP produced by glucose metabolism increased cADPR accumulation in transgenic islets. Glucose- and ketoisocaproate-induced but not tolbutamide- nor KCl-induced insulin secretions from transgenic islets were 1.7-2.3-fold higher than that of control. In glucose-tolerance tests, the transgenic serum insulin level was higher than that of control. The present study provides the first evidence that CD38 has a regulatory role in insulin secretion by glucose in beta cells, suggesting that the Ca2+ release from intracellular cADPR-sensitive Ca2+ stores as well as the Ca2+ influx from extracellular sources play important roles in insulin secretion.

ADP-ribosyl Cyclase↗
PubMed1995

Morphological abnormalities in the hippocampus of the weaver mutant mouse.

The lamination of the hippocampus in the homozygous B6CBA weaver mouse (wv/wv) was compared with that in normal B6CBA littermates (+/+) and C57BL/6J mice using Nissl and Timm's staining. In Nissl-stained preparations, the normal littermates exhibit a compact, regular arrangement of pyramidal cells in area CA3 of the hippocampus. In contrast, in homozygous weaver mutant mice, the pyramidal cell layer of area CA3 frequently appears to be thicker than normal with an apparent increase of neuropil, as evidenced by the presence of cell-free spaces within the layer. Also, small ectopic clusters of pyramidal cells and sometimes the subdivision of the pyramidal cell layer into 2 or 3 layers were found throughout the dorsoventral extent of the hippocampus. In Timm's stained preparations of the normal mouse hippocampus, two clearly separated bundles of axons were seen emerging from the hilus: one bundle running above the pyramidal cell layer of area CA3 (i.e., the suprapyramidal mossy fiber layer, SPMFL), and the second bundle running below the pyramidal cell layer (i.e., the infrapyramidal mossy fiber layer, IPMFL). In contrast, in some homozygous weaver mice, the origin of the mossy fiber bundles is clearly different from normal; specifically, mossy fibers emerge in a diffuse fashion from the area between suprapyramidal and infrapyramidal mossy fiber layers. In other weaver mice, short, discontinuous bundles diverge from the infrapyramidal mossy fiber layer and invade the thickened pyramidal cell layer. In addition, ectopic pyramidal cells are situated below the IPMFL in area CA3. The morphological changes observed in hippocampus of weaver mutants are likely to be secondary to a more basic genetic defect.

Animals↗
PubMed1995

Magnetic resonance imaging of femoral marrow in patients with myelodysplastic syndromes or leukemia.

We evaluated magnetic resonance imaging (MRI) of femoral marrow in 85 untreated adult patients with myelodysplastic syndromes (MDS) (N = 27), aplastic anemia (N = 9), and leukemia (N = 49). Images of femoral marrow were obtained using a T1-weighted spin-echo (SE) method and a short T1 inversion recovery (STIR) technique. In patients with MDS, the change in MRI pattern from a fatty or nodular pattern to a uniform pattern correlated with disease progression. Evolution to acute leukemia in MDS patients was associated with a higher signal intensity on STIR images (lower signal intensity on T1-weighted SE images) and an extended area of involvement. The femoral marrow in patients with de novo acute myeloid leukemia (AML) showed increased signal and varied patterns (scattered to uniform) on STIR images. However, the faint pattern (grade 4a) was characteristic of M2 AML. In patients with chronic myelogenous leukemia (CML) in the chronic phase, increased leukemic mass was represented by replacement of the femoral marrow with a region of abnormal signal intensity. The extent of involved areas in these CML patients correlated with the spleen size. This study indicates that MRI of femoral marrow is an important tool for the accurate diagnosis and management of patients with MDS and leukemia that may function as an adjunct to bone marrow aspiration and biopsy.

Adipose Tissue↗
PubMed1995

Ultrastructure of developing muscle in the upper limbs of the human embryo and fetus.

BACKGROUND: The ultrastructure of the myogenesis, which proceeds along with the appearance of muscle-specific proteins and isozymes, has not been fully described in the upper limb of staged human embryos. METHODS: Eight human embryos (Carnegie stage 14-22) and two fetuses (11 and 12 weeks of gestation) were fixed with 5% glutaraldehyde, 4% paraformaldehyde, and 0.2% picric acid in 0.1 M phosphate buffer, pH 7.2. The upper limbs were dissected out and processed for transmission electron microscopy, and sections of the biceps brachii muscle were cut and examined. RESULTS: At stage 14, the myoblasts were loosely scattered in the ventral proximal region of the upper limb bud and had a small amount of cytoplasm with a few intracellular organelles. At stage 16, the myoblasts were spindle shaped and oriented parallel to the axis of the upper limb bud. These cells had irregularly shaped nuclei with prominent nucleoli, rough endoplasmic reticulum (ER), and mitochondria, but no myofilaments were observed. At stages 17-19, rough ER, free ribosomes, and mitochondria increased in number and thick and thin filaments with faint Z-lines appeared in the peripheral cytoplasm of the myotube. The plasma membranes of some neighboring myotubes were continuous, suggesting that these cells were in the initial stages of the fusion process. At stage 22, the striated pattern of the myofilaments became evident and tubular structures appeared around them and near the plasma membrane. In the fetus at the 11th week, the basal lamina began to surround the myotubes, and T-tubules with sarcoplasmic reticulum were observed. Dyads and triads were observed in the myotube of the 12th week fetus. CONCLUSION: These findings suggest that rapid myogenesis occurs during the late embryonic period in human upper limbs and that the ultrastructural characteristics of mature myotubes are established during the early fetal period.

Arm↗
PubMed1995

Histocytochemical and immunohistochemical studies related to the role of glycogen in human developing digestive organs.

To elucidate the role of glycogen in the epithelium of developing digestive organs, we investigated the appearance of glycogen and glycogen phosphorylase (GP) in these organs. We studied 64 externally normal human embryos at Carnegie stages 13-23 (5.1-28.0 mm in crown-rump length, 4-8 weeks of gestation) by histocytochemical staining for glycogen and immunohistochemical staining with antibodies against two isoenzymes of GP: brain-type (BGP) and muscle-brain-type (MBGP) GP. At stage 13, glycogen appeared in the epithelium of the digestive tract and the parenchyma of the pancreas. As development advanced, glycogen granules increased in number and size in these tissues, and they became evenly distributed in the epithelium of the digestive tract as either single particles or aggregates, as deduced by electron microscopy at late embryonic stages. Immunoreactivity specific both for BGP and for MBGP was detected in the digestive tract and the pancreas from stage 13. As development advanced, both BGP- and MBGP-immunoreactive cells increased in number and in immunoreactivity, and the number of MBGP-immunoreactive cells became larger than that of BGP-immunoreactive cells. By contrast, in hepatic cells, which serve as a major storage site for glycogen in adults, glycogen was detected only from stage 20, in smaller amounts, without formation of aggregates, and no immunoreactivity specific for BGP or MBGP was apparent throughout the embryonic stages examined. Thus, in the epithelium of the digestive tract and the parenchyma of the pancreas, but not in hepatic cells, the appearance and localization of GP coincided almost exactly with that of glycogen. These observations suggest that glycogen in the epithelium of the digestive tract and the parenchyma of the pancreas has not only been synthesized but also degraded from an early embryonic period and may, thus, be related to active cellular metabolism that is specific for embryonic development, including proliferation of the epithelium and interactions between epithelium and mesenchyme.

Digestive System↗