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H Namba

Publications and source records attributed to H Namba.

At least 145 records · Page 8Linked to original sources

Correlation between suppression of c-myc and antiproliferative effect of transforming growth factor-beta 1 in thyroid carcinoma cell growth.

The growth regulatory activity of transforming growth factor-beta 1 (TGF beta 1) was studied in a clonal strain of thyroid papillary carcinoma cell (NPA). Despite the presence of TGF beta 1 and its receptor messenger RNA in thyroid carcinoma, the molecular mechanism of TGF beta 1 action on cell growth of thyroid carcinoma has not yet been elucidated. Exogenously added TGF beta 1 inhibited DNA synthesis and cell growth in a dose- and time-dependent manner at concentrations of 0.1-10 ng/ml. TGF beta 1 inhibited not only basal but also fetal bovine serum-stimulated cell proliferation. Steady state levels of c-myc messenger RNA transcripts were inhibited by TGF beta 1 after 0.5-h treatment. Antisense, but not sense, c-myc oligodeoxynucleotides also caused suppression of NPA cell growth in a dose-responsive manner. Transfection studies of the 5'-up-stream flanking region (UFR) of c-myc/chloramphenicol acetyltransferase chimera genes suggest the presence of a TGF beta 1-responsive DNA element in the 2.3-kilobase c-myc 5'-UFR. Deletion mutant studies indicate the element lies between -106 to 70 relative to the P1 transcription start site. Studies with the gel mobility shift assay using 23-basepair double strand DNA showed the presence of at least two nuclear factors in NPA cell. TGF beta 1 treatment did not cause any alteration in TGF beta 1-induced mobility; however, the reduction of a positive band was selectively observed during 30 min to 2 h after treatment with TGF beta 1. In contrast, the position and intensity of another band were not altered by TGF beta 1 treatment. These results demonstrate that the inhibition of a nuclear factor binding to the c-myc 5'-UFR and subsequent suppression of c-myc gene expression are directly involved in the antiproliferative action of TGF beta 1 in NPA cell growth.

Base Sequence↗

Role of intracellular Ca2+ pools in the effects of halothane and isoflurane on vascular smooth muscle contraction.

We examined the effect of halothane and isoflurane on contraction in the vascular smooth muscle of rat thoracic aorta simultaneously with the cytosolic Ca2+ levels ([Ca2+]i). Isolated spiral strips of rat thoracic aorta were suspended for isometric tension recordings in physiologic salt solution. The [Ca2+]i was measured concomitantly using fura-2-Ca2+ fluorescence. Muscle tension was elicited either by 51 mM K+ solution or 30 nM norepinephrine, and the muscle was exposed to 0%, 1%, 2%, 3% halothane or 0%, 1%, 2%, 3%, 4% isoflurane. The effects of the anesthetics were compared with the effects of verapamil, an L-type voltage-dependent Ca2+ channel blocker, also administered during K(+)-induced muscle contraction. In another series, the effects of the anesthetics on caffeine- or norepinephrine-induced muscle contraction were determined in Ca(2+)-free solution. Finally, 3% halothane or 4% isoflurane was administered during K(+)-induced contraction in muscle strips pretreated with ryanodine and caffeine. During K(+)-induced contraction, halothane evoked a transient increase followed by a decrease in both muscle tension and [Ca2+]i. The biphasic change in muscle tension was not elicited by isoflurane or by any agent under norepinephrine-induced contraction. Both halothane and isoflurane ultimately suppressed both K(+)- and norepinephrine-induced increases in muscle tension and the [Ca2+]i in a concentration-dependent manner. The slopes of the [Ca2+]i-tension regression lines under the two anesthetics were significantly steeper than that under verapamil during K(+)-induced contraction. Halothane, but not isoflurane, augmented 4 mM caffeine-induced tension and [Ca2+]i transients in the Ca(2+)-free solution in a concentration-dependent manner. However, neither anesthetic influenced norepinephrine-induced tension and [Ca2+]i transients. In the muscle strips pretreated with ryanodine and caffeine, the difference observed between the anesthetics was abolished. In conclusion, halothane, but not isoflurane, enhances Ca2+ release predominantly from the caffeine-releasable Ca2+ stores in vascular smooth muscle; this release may modify the effect of halothane. The intracellular Ca2+ pools can be affected differently by volatile anesthetic drugs, depending on the nature of the stimulus for smooth muscle contraction.

Animals↗

Assessment of the brain areas perfused by superselective intra-arterial chemotherapy using single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime--technical note.

The brain areas perfused by superselective intra-arterial (i.a.) chemotherapy were assessed using single photon emission computed tomography (SPECT) with technetium-99m-hexamethyl-propyleneamine oxime (99mTc-HMPAO). A superselective catheter was introduced into the anterior, middle, or posterior cerebral artery of patients with malignant glioma for i.a. chemotherapy. 99mTc-HMPAO was subsequently injected via the same catheter used for chemotherapy, and a higher dose of 99mTc-HMPAO was injected intravenously to obtain adequate background brain images. Comparison of the SPECT images with magnetic resonance images could confirm complete perfusion of the tumor tissue. In two patients with malignant glioma, regions of interest were selected in the peritumoral brain area and a reference brain area, and the radioactivity was measured. The concentration of 99mTc-HMPAO was about 50 times higher in tissue perfused by superselective injection into anterior or middle cerebral artery compared to intravenous injection. 99mTc-HMPAO SPECT is readily available in many institutions and the information provided is useful for planning more effective and safe i.a. chemotherapy.

Adolescent↗

Morphological and physiological bases of crayfish local circuit neurones.

As the subject of neuroethological studies, arthropods offer several advantages to elucidate the neural processes that generate and control behavioural acts. The relative simplicity of their neural organization and their identifiable neurones are particularly advantageous. The crayfish, Procambarus clarkii, uropods are paired appendages of the last abdominal segment that show bilateral closing movement in response to mechanical stimulation. This movement, the avoidance "dart" response, is mediated by a cascade and parallel organization of local circuit neurones in the terminal abdominal ganglion. Thirty intersegmental ascending interneurones and 20 spiking local interneurones have been identified both morphologically and physiologically. They receive exteroceptive inputs directly from the sensory afferents. Two complementary groups of unilateral nonspiking local interneurones have also been functionally identified. They exert fine control over the wide range of activity of motor neurones in a graded and sustained manner. These nonspiking interneurones form opposing and parallel pathways that are essential in modulating the pattern of movement of the uropods.

Animals↗

[Reoperations for valvular heart disease through repeated median sternotomy incision].

One thousand and three hundred patients underwent open heart surgery for acquired valvular diseases in our hospital from 1952 through December 1993. There were 105 reoperative cases through repeated median sternotomy incision and 52 cases of prosthetic valve replacement by the same operator in the last 5 years. We studied technical procedures by these reoperative experience. There was only one case (1.9%) of hospital death in replacement cases. We believe that repeated open heart surgery for acquired valvular diseases should be done prior to deterioration of patient's clinical condition. We had to pay attention to facilitate mobilization of right atrium and aortic root in the aortic and mitral valvular reoperations. To decrease operative mortality of prosthetic valve replacement, each operative techniques were necessary by the reasons for reoperation.

Adolescent↗

Physiology and morphology of spiking local interneurons in the terminal abdominal ganglion of the crayfish.

Not only nonspiking local interneurons but also spiking local interneurons in the terminal abdominal ganglion of the crayfish (Procambarus clarkii Girard) contribute to form the motor output of the uropod. In this study, 14 spiking local interneurons are identified by their gross morphology and physiological properties including the sensory inputs from the uropod and premotor output onto the uropod motor neurons on both sides. Morphologically, they are divided into three groups based on the position of their somata: anterior, medial, and posterior. The main branches of interneurons in each group are usually extended on the side contralateral to the soma, or they have profuse bilateral branches. Physiologically, all of them receive excitatory inputs from the afferents innervating the exopodite on the side ipsilateral their main branches. They are usually silent, and spike only in response to sensory stimulation. The majority of them (11 out of 14 neurons) have output effects on the uropod motor neurons that elicit reciprocally closing pattern. They increased the activity of the closer motor neurons and decreased the activity of the opener motor neurons. Only one interneuron inhibits the closer motor neurons. The remaining two interneurons coactivate both the antagonistic motor neurons. Since the reciprocal closing pattern of the uropod motor neurons is elicited in response to sensory stimulation of the uropod, spiking local interneurons may initiate this local reflex circuit. They detect the initiation of the stimulus and convey signals from the sensory to the motor side.

Animals↗

[Thyroid and radiation].

The topic "Thyroid and Radiation" is both an old and a new area to be solved by human beings. The thyroid is an organ that is usually susceptible to exposure to ionizing radiation, both by virtue of its ability to concentrate radioiodine (internal radiation) and by routine medical examination: Chest X-ray, Dental X-ray, X-irradiation of cervical lymphnodes etc. (external radiation). Iodine-131 is widely used for the therapy of Graves' disease and thyroid cancers, of which the disadvantage is radiation-induced hypothyroidism but not complications of thyroid tumor. The thyroid gland is comparatively radioresistant, however, the data obtained from Hiroshima, Nagasaki and Marshall islands indicates a high incidence of external radiation-induced thyroid tumors as well as hypothyroidism. The different biological effects of internal and external radiation remains to be further clarified. Interestingly, recent reports demonstrate the increased number of thyroid cancer in children around Chernobyl in Belarus. In this review, we would like to introduce the effect of radiation on the thyroid gland at the molecular, cellular and tissue levels. Furthermore the clinical usefulness of iodine-131, including the safety-control for radiation exposure will be discussed.

Cell Division↗

Autocrine/paracrine function of parathyroid hormone-related peptide in rat osteoblast-like cells.

Parathyroid hormone-related peptide (PTHrP) may be synthesized in or near its target tissues and acts by autocrine and/or paracrine fashions. The rat clonal strain of the osteoblast-like cell, ROS 17/2.8-5, can express low levels of PTHrP in the cytoplasm; however, the autocrine function of PTHrP in ROS cells has not yet been clarified. We created PTHrP expression vectors and transfected them into cells in order to elucidate the functional role of PTHrP on their own target cells. Sense and antisense rat PTHrP expression vectors (pSV2 neo-ECE-rPLP) were transfected into ROS cells independently and cultured for 72 hours. Cells overexpressing PTHrP were detected by immunocytochemical analysis and confirmed by Northern blot analysis, respectively. These transfected cells demonstrated mitogenic activity as determined by BrdU uptake staining. These findings suggest the functional role of PTHrP on their own PTHrP expressing cells via an autocrine/paracrine fashion. These PTHrP-overexpressing ROS cells provide a model in vitro system to clarify the mechanism by which PTHrP acts in an autocrine/paracrine fashion.

Animals↗

Protein phosphatase type 2B (calcineurin)-mediated, FK506-sensitive regulation of intracellular ions in yeast is an important determinant for adaptation to high salt stress conditions.

To assess the physiological function of Ca(2+)-dependent protein phosphatase (PP2B) in the yeast Saccharomyces cerevisiae, the phenotypes of PP2B-deficient mutants were investigated. Although PP2B was dispensable for growth under normal conditions, the mutations did, however, cause growth inhibition under certain stress circumstances. The growth of the mutants was inhibited by NaCl and LiCl, but not by KCl, CaCl2, MgCl2 or nonspecific osmotic stresses. Upon shift to high NaCl medium, intracellular Na+ levels of both wild type yeast and the mutants initially increased at a comparable rate. However, internal Na+ in wild type cells started to decline more rapidly than the mutant cells during cultivation in high NaCl medium, indicating that PP2B is important in maintaining a gradient across the membrane. The protection against salt stress was achieved, at least in part, by the stimulation of Na+ export. The maintenance of a high level of internal K+ in high NaCl medium was also PP2B-dependent. In the presence of the immunosuppressant FK506, the growth behaviour and intracellular Na+ and K+ of wild type cells in high NaCl medium became very similar to those of the PP2B-deficient mutant in a manner dependent on the presence of the FK506 binding protein.

Adaptation, Physiological↗

Intra-arterial mannitol infusion in the chemotherapy for malignant brain tumors.

To assess whether therapeutic efficacy is related to the intra-arterial (IA) mannitol infusion prior to ACNU and cisplatin (CDDP) for malignant brain tumors, the survival time of patients with and without mannitol infusion was compared. Ninety-eight patients were randomly assigned to either a mannitol infusion group (group A) or a non-mannitol infusion group (group B); 34 with malignant gliomas (18 in group A and 16 in group B) and 64 with brain metastases (36 in group A and 28 in group B). During radiotherapy, ACNU and CDDP at a dose of 100 mg/body were given through the common carotid artery at a rate of 20 mg/min. In group A, 50 ml of 20% mannitol was injected intra-arterially at a rate of 50 ml/min immediately prior to the injection of chemotherapeutic agents. Of the patients with malignant gliomas, the median survival time (MST) was 52 weeks for all 34 cases, 68 weeks for group A, and 47 weeks for group B. Survival analysis showed no significant differences between the two treatment groups. Of the patients with brain metastases, the MST was 40 weeks for all 64 cases, 47 weeks for group A, and 24 weeks for group B; the survival time was significantly longer in group A as compared to group B (p < 0.05). This study has demonstrated that, for the patients with brain metastases, IA mannitol infusion provided a survival benefit in the IA chemotherapy employing ACNU and CDDP. In contrast, IA mannitol infusion offered no survival benefit to the patients with malignant gliomas.

Adolescent↗

Skeletal muscle glucose transporter gene expression is not affected by injecting growth-hormone-secreting cells in young rats.

To elucidate the diabetogenic effect of growth hormone on glucose metabolism the regulation of glucose transporter (GLUT) gene expression was examined in rat skeletal muscles. Female Wistar-Furth rats were implanted subcutaneously with growth-hormone-producing pituitary tumour (GH3) cells. Animals were killed 4 or 9 weeks after GH3 cell injection. Although body weight, serum growth hormone and insulin-like growth factor I levels were remarkably elevated during the 4-9 week period, serum blood glucose levels were within normal range. Muscles were obtained from the quadriceps muscle, diaphragm and heart, respectively. Northern blot analysis and Western blot analysis were performed using specific cDNA probes and antibodies. During the 4-9 week period, the levels of muscle GLUT1 and 4 mRNA (corrected by beta-actin mRNA level) in each muscle from the rats injected with tumour cells were not significantly different from those of control rats. Chronic elevation of growth hormone in these rats did not cause any change in GLUT 1 and 4 expression compared to the controls during the euglycaemic period. These results provide the first evidence that chronic growth hormone elevation itself does not affect a key gene of in vivo glucose metabolism.

Animals↗

Demonstration of abnormal perfusion in the pons with high resolution SPECT and technetium-99m HMPAO in a patient with acoustic neuroma.

We detected a regional defect in the pons with ipsilateral cerebellar hypoperfusion in a patient with acoustic neuroma by brain SPECT with 99mTc HMPAO. A high spatial resolution SPECT system with three detectors equipped with fan-beam collimators was employed. This is the first report of a defect in the brainstem being visualized by perfusion SPECT and this method could make it possible to clarify the cause of a remote effect on the cerebellar perfusion by injury to the brainstem.

Cerebellum↗

Modulation of pituitary insulin-like growth factor-I bindings in rats bearing somatomammotrophic tumors.

To clarify the hormonal regulation of pituitary insulin-like growth factor-I (IGF-I) bindings, we examined the continuous effect of growth hormone (GH) on [125I] IGF-I binding sites, using rats bearing transplantable GH-secreting rat pituitary tumor cells. A total of 24 female Wistar-Furth rats (4-week old) was divided into four groups (n = 6). The first group rats were control (C). The second group rats were injected subcutaneously with 3 x 10(6) GH3 pituitary tumor cells (GH). The third group rats were thyroidectomized (Tx) and the fourth were dual-treated (GHTx). The brain, pituitary gland, liver, and kidney were immediately subjected to quantitative receptor autoradiography after a 4-week treatment period. Using kinetic experiments, GH rats had higher Bmax values of specific [125I] IGF-I binding sites in the anterior pituitary gland and Tx rats had lower Bmax values than control rats. Two-way analysis of variance among the 4 groups was examined. The effects of both GH and Tx treatment on [125I] IGF-I binding Bmax were observed only in the anterior pituitary gland and not in the other tissues examined. There were no differences in the Kd values of the binding sites. These data indicate that continuous GH excess selectively up-regulates the number of pituitary IGF-I binding sites in vivo, and that this may play a role in feedback regulation of the GH-IGF-I axis.

Animals↗

Retinoic acid inhibits human thyroid peroxidase and thyroglobulin gene expression in cultured human thyrocytes.

The effect of retinoic acid (RA) on thyroid peroxidase (TPO) and thyroglobulin (Tg) gene expression was investigated in cultured human thyrocytes. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH 5mU/ml and RA 0, 0.01, 0.1, 1.0 microM for 72 h respectively. The samples were then subjected to Northern gel analysis. Northern gel analysis using the specific cDNA probes showed that RA suppressed the accumulation of TPO and Tg mRNA stimulated by TSH in a time- and dose-responsive manner. Furthermore, RA inhibited forskolin and 8-Bromo-cyclic-AMP-induced TPO and Tg gene expression, suggesting a distal action site for these cAMP mediated gene expressions. Immunoprecipitation analysis using the specific monoclonal antibodies showed that TSH increased newly synthesized 100, 75, 36-kDa [35S] TPO. The increased de novo TPO was markedly inhibited by RA. Tg secretion from monolayer cultures was measured by radioimmunoassay. RA also inhibited TSH-induced Tg secretion in a dose dependent manner. RA did not affect [3H] thymidine uptake into primary cultured human thyrocytes. In conclusion, RA inhibits the synthesis of TPO and Tg via the suppression of thyroid-specific gene expression although the exact site of RA action on these genes in human thyroids remains to be further elucidated. These results suggest that RA may play a regulatory role in Tg and TPO gene expression, subsequently resulting in the suppression of thyroid hormone synthesis.

8-Bromo Cyclic Adenosine Monophosphate↗

Effects of halothane and isoflurane on cytosolic calcium ion concentrations and contraction in the vascular smooth muscle of the rat aorta.

BACKGROUND: Halothane and isoflurane have been reported to suppress the contraction of vascular smooth muscle, although the exact mechanism has not been explained fully. This study examined the effect of halothane and isoflurane on cytosolic calcium ion (Ca2+) concentrations ([Ca2+]cyt), which was measured simultaneously with muscle tension in the vascular smooth muscle of the rat aorta to improve the understanding of the anesthetic's effect on vascular smooth muscle. METHODS: Isolated spiral strips of rat thoracic aorta were suspended for isometric tension recordings in physiologic salt solution. The [Ca2+]cyt was measured concomitantly by using fura-2-Ca2+ fluorescence. During exposure to 0%, 1%, 2%, or 3% halothane or 0%, 2%, or 4% isoflurane, increases in muscle tension and [Ca2+]cyt induced by 32.8 mM K+ or 30 nM norepinephrine were measured and compared with the reference values. In the other series, the 3% halothane-induced increase in [Ca2+]cyt was measured in Ca2+)-free solution without and with a pretreatment of ryanodine, caffeine, or norepinephrine. RESULTS: Halothane and isoflurane increased resting-state [Ca2+]cyt, although only 3% halothane elicited a transient increase in muscle tension during the resting state. By contrast, both anesthetic agents attenuated the high K(+)- and norepinephrine-induced increases in [Ca2+]cyt and muscle tension in a concentration-dependent manner. During 3% halothane or 4% isoflurane exposure, the pretreatment of the muscle strip with a 10(-6)-M dose of Bay K 8644 augmented the high K(+)-induced increase in [Ca2+]cyt to the level observed in the control (0% anesthetic exposure) state. However, the increase in muscle tension in the presence of Bay K 8644 was low; it was still attenuated from the control level during 3% halothane or 4% isoflurane administration. These results indicate that, not only [Ca2+]cyt-dependent, but also [Ca2+]cyt-independent, mechanisms are involved in the anesthetic-induced suppression of smooth muscle contraction. A 3% halothane-induced increase in [Ca2+]cyt was observed in the Ca(2+)-free solution even when the muscle strip was pretreated with a 10(-6)-M dose of ryanodine and a 20-mM dose of caffeine, whereas it was abolished completely after the muscle strip was pretreated with ryanodine, caffeine, and 100 nM norepinephrine. These results indicate that halothane can release Ca2+ from an intracellular Ca2+ store other than the caffeine-releasable site. CONCLUSIONS: Halothane and isoflurane have multiple effects on the [Ca2+]cyt and induce [Ca2+]cyt-dependent and [Ca2+]cyt-independent suppression of the contraction in the vascular smooth muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Expression of parathyroid hormone related peptide in human pituitary tumours.

The presence of parathyroid hormone related peptide (PTHrP) was studied in 20 patients with pituitary adenomas and one patient with pituitary adenocarcinoma. PTHrP expression was shown in almost all of the pituitary adenomas (95%) and in 100% (n = 7) growth hormone producing pituitary adenomas. A metastatic lesion from a pituitary growth hormone producing adenocarcinoma revealed strongly expressed PTHrP. It was weakly detected in normal pituitary cells in all of the specimens (n = 10). There was no significant correlation, however, between PTHrP expression and the clinical or pathological features of growth hormone producing tumours. Apart from an important role in the physiological function of the pituitary gland, PTHrP may be closely related to somatotroph tumorigenicity.

Adenocarcinoma↗