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Biomedical subjects

K Shimamura

Publications and source records attributed to K Shimamura.

At least 109 records · Page 6Linked to original sources
PubMed1995

Effects of chronic treatment with carvedilol on abnormalities of endothelium-dependent relaxation and structure of endothelium in resistance arteries of SHRSP.

1. This study investigated the effects of chronic treatment with carvedilol, a beta-blocking agent with an alpha-blocking activity, on blood pressure, endothelium-dependent relaxation and the endothelial structure of the mesenteric resistance artery in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Chronic treatment with carvedilol at a dose range of 30-120 mg/kg per day lowered systolic blood pressure of SHRSP from 234.9 +/- 3.3 to 198.7 +/- 3.1 mmHg at 16 weeks of age. 3. Acetylcholine-induced endothelium-dependent relaxation was impaired in the mesenteric artery from SHRSP and high concentrations of acetylcholine produced contractions. The impairment of the relaxation was abolished in the presence of indomethacin. Carvedilol treatment improved the impairment in the preparation from SHRSP. The structural abnormality of endothelium was observed in the preparation from SHRSP. The abnormality could be prevented by the antihypertensive treatment. 4. These results suggest that the impairment of endothelium-dependent relaxation in the preparation from SHRSP is due to the corelease of an endothelium-derived contracting factor which is considered to be a product of cyclo-oxygenase pathway of arachidonic acid cascade and that the impairment can be prevented by the antihypertensive treatment with carvedilol.

Acetylcholine↗
PubMed1995

Longitudinal organization of the anterior neural plate and neural tube.

Over the last century, several morphological models of forebrain organization have been proposed that hypothesize alternative topological solutions for the relationships of the histogenic primordia. Central to all of these models are their definitions of the longitudinal axis and the longitudinal organization of the neural plate and neural tube. To understand the longitudinal organization of the anterior brain, we have sought to identify molecular properties that are continuous along the entire longitudinal axis of the embryonic CNS. In this essay, we describe studies of the expression of several genes in the mouse between 7.5 (presomite stage) and 10.5 days post coitum (dpc) that provide evidence for the trajectory of the anterior-posterior axis and the longitudinal organization of the anterior CNS. Specifically, we report that the expression of noggin, sonic hedgehog and Nkx-2.2 define longitudinal columns of cells that are present along the entire CNS axis. Within the forebrain, the expression of these genes, as well as that of Nkx-2.1 and BF-1, are in distinct longitudinal regions in the neural plate and tube. We demonstrate that the earliest longitudinal axon pathways of the forebrain are spatially correlated with the longitudinal domain defined by Nkx-2.2. Finally, expression of the former genes, and Otx-1 and Emx-2, suggests that the cephalic neural plate is organized into molecularly distinct domains delimited by longitudinal and transverse borders; these results provide a foundation for defining the mechanisms that pattern the neural plate.

Animals↗
PubMed1995

Changes in lipid peroxide and antioxidant enzyme activities in corpora lutea during pseudopregnancy in rats.

This study investigated the involvement of lipid peroxidation and antioxidant enzymes in the regulation of luteal function in pseudopregnant rats. The activities of superoxide dismutase (SOD), a specific scavenger of superoxide radicals, and glutathione peroxidase, a scavenger of hydrogen peroxide, and lipid peroxide concentrations were measured in the corpus luteum on days 1, 3, 5, 7, 9, 11 and 13 of pseudopregnancy. The activity of SOD in the corpus luteum gradually increased until day 9 of pseudopregnancy and decreased thereafter, in a similar manner to serum progesterone concentration. Glutathione peroxidase activity significantly increased from day 1 to day 3 and remained high until day 11 of pseudopregnancy. The concentrations of lipid peroxides in the corpus luteum increased from day 3 to day 13 of pseudopregnancy. The involvement of prostaglandin F2 alpha (PGF2 alpha) in the production of lipid peroxides in regression of the corpus luteum was investigated by administering PGF2 alpha (3 mg kg-1, s.c.) or saline on days 7, 9 and 12 of pseudopregnancy. Each group of rats was autopsied 2 h later, and SOD activity, glutathione peroxidase activity and the concentration of lipid peroxides in the corpus luteum were determined. PGF2 alpha significantly increased lipid peroxide concentrations in the corpus luteum on days 7, 9 and 12 of pseudopregnancy (approximately twofold increases on days 7 and 9, and a fivefold increase on day 12, compared with the control that received saline). The activity of SOD in the corpus luteum was significantly increased by PGF2 alpha on days 7 and 9, but not on day 12, of pseudopregnancy. PGF2 alpha did not cause any significant changes in glutathione peroxidase activity in the corpus luteum on days 7, 9 and 12 of pseudopregnancy. It is concluded that lipid peroxides play an important role in regulating luteal function in pseudopregnant rats.

Animals↗
PubMed1995

Effects of NG-nitro-L-arginine on alpha-agonists-induced contraction of aortae from Wistar Kyoto rats and stroke-prone spontaneously hypertensive rats.

Differences in the influences of endothelium-derived nitric oxside (NO) on alpha-agonists-induced contraction in the aortae of spontaneously hypertensive and normotensive rats were studied by blocking NO synthesis with NG-nitro-L-arginine (L-NNA). L-NNA potentiated the contraction induced by noradrenaline. The potentiation was smaller in the preparation from stroke-prone spontaneously hypertensive rats (SHRSP) than in the preparation from Wistar Kyoto rats (WKY). Similar potentiation was observed in the contraction induced by phenylephrine; the potentiation was also smaller in the preparation from SHRSP. alpha 2-agonists, clonidine and UK-14304 induced dose-dependent contraction only in the presence of L-NNA. The dose-response curves for alpha 2-agonists in SHRSP aorta were different from those in WKY aorta; the maximum tension was observed at the concentration of 10(-6) M in the preparation from WKY, while the contraction further increased up to 10(-4) M in the preparation from WKY. Noradrenaline, clonidine and UK-14304 but not phenylephrine induced relaxation which was blocked by L-NNA. The relaxation was impaired in the preparation from SHRSP in greater extent than that by acetylcholine. It is suggested that basic or noradrenaline-stimulated NO release from endothelium decreased in the preparation from SHRSP and that alpha 2-adrenoceptor of both the endothelium and smooth muscle may be altered in the preparation from SHRSP.

Adrenergic alpha-Agonists↗
PubMed1995

Pulmonary fibrosis and sea-blue histiocyte infiltration in a patient with primary myelofibrosis.

The authors present the case of a 73 year old man with primary myelofibrosis, pulmonary fibrosis, and acquired sea-blue histiocytosis, who died of respiratory failure. Pathology of the lungs revealed infiltration by sea-blue histiocytes, and fibrosis in the alveolar septa, and clumps of these cells filling the alveolar spaces. Megakaryocytes were also occasionally observed in the alveolar capillaries.

Aged↗
PubMed1994

Mouse alpha N-catenin: two isoforms, specific expression in the nervous system, and chromosomal localization of the gene.

We isolated cDNAs encoding mouse homologues of chicken alpha N-catenin, a protein associated with the cadherin cell adhesion molecules, and identified two isoforms of this protein. One isoform (alpha N-catenin I) was identical to the chicken alpha N-catenin that had previously been identified, and the other (alpha N-catenin II) differed in having a 48-amino acid insertion in its C-terminal region. The ratio of the two isoforms changed during development; the isoform II was more abundant than the other in earlier embryonic stages, whereas isoform I was predominant in the adult stage. Immunostaining and in situ hybridization analyses revealed that the mouse alpha N-catenin was expressed almost exclusively in the nervous system. During embryogenesis, alpha N-catenin was first detected in nerve fibers of cranial and dorsal root ganglia and also in early neurons in the neural tube, including motor neurons. Thereafter, the expression of this protein occurred in various regions of the nervous system. Neurons, in general, strongly expressed alpha N-catenin, especially in their axonal fibers. On the other hand, the expression in glial cells varied with the region. For example, the ependymal layers of the neural tube generally expressed low levels of alpha N-catenin except at the inner limiting membrane facing the central canal, whereas the floor and roof plate exhibited strong expression of this protein at various portions of the central nervous system. The choroid plexus was devoid of alpha N-catenin. In the alpha N-catenin-negative regions, another subtype of alpha-catenin, alpha E-catenin, was expressed. Concerning nonneural tissues, alpha N-catenin was expressed only in some local mesenchymal cell clusters and the lens fibers. These results suggest that alpha N-catenin plays specific roles in neural cell-cell interactions. We also localized the mouse alpha N-catenin gene to chromosome 6.

Amino Acid Sequence↗
PubMed1994

Preferential localization of c-kit product in tissue mast cells, basal cells of skin, epithelial cells of breast, small cell lung carcinoma and seminoma/dysgerminoma in human: immunohistochemical study on formalin-fixed, paraffin-embedded tissues.

Eighteen hundred and eighty-four cases of human solid tumours and 833 samples of normal human tissues, formalin-fixed and paraffin-embedded, were examined immunohistochemically for expression of c-kit oncogene product using polyclonal antibody against synthesized c-kit peptide. Seminoma/dysgerminoma and small cell lung carcinoma (SCLC) show preferential c-kit expression at 92% and 36% frequency, respectively, whereas only sporadic cases of cervical carcinoma and non-SCLC lung carcinoma show c-kit positivity. A normal tissue counterpart positive for c-kit product is detected in the testis (spermatocyte) and ovary (oocyte) but not in the lung or the cervix. In contrast, normal epithelial cells of the breast, skin basal cells and tissue mast cells harbour c-kit product, but transformed cells of the former two are largely deficient in the c-kit protein. One hundred and thirty-nine neuroendocrine tumours and 39 non-pulmonary small cell carcinomas were all negative, except for two cases of neuroblastoma. This indicates a distinct character for SCLC in c-kit expression. The c-kit product may be a useful marker in diagnostic pathology of seminoma/dysgerminoma and SCLC among human solid tumours, and in distinction of SCLC from non-pulmonary small cell carcinoma.

Adult↗
PubMed1994

Immunoelectron microscopic localization of E-cadherin in dorsal root ganglia, dorsal root and dorsal horn of postnatal mice.

Sensory neurons and associated glial cells are known to express the cell-cell adhesion molecule E-cadherin. The cellular and subcellular localization of this molecule in the dorsal root ganglion, dorsal root, and spinal cord of postnatal mice was studied by the pre-embedding immunoelectron microscopic labelling technique. In the dorsal root and the superficial layer of the dorsal horn, a subset of fasciculating unmyelinated axons expressed E-cadherin at their axon-axon contacts at all ages studied, and these axons were clustered together and segregated from E-cadherin-negative axons. In contrast, pre-myelinating large-diameter axons in P2 mice as well as myelinated axons in mice from P14 to adulthood were E-cadherin-negative. Glial cells also expressed E-cadherin: In the dorsal root ganglia, all of the satellite cells expressed E-cadherin at contact sites with neurons, other satellite cells, and basal lamina, at all ages studied. In dorsal roots from P14 to adulthood, myelin-forming Schwann cells expressed E-cadherin at the outer mesaxons and the contact sites with basal lamina. Non-myelin-forming Schwann cells occasionally stained for this molecule at contact sites with the plasma membrane of E-cadherin-positive axons and at other sites. These results strongly suggest that E-cadherin plays an important role in the selective fasciculation of a particular subset of unmyelinated sensory fibres, and also in glial cell contacts.

Animals↗
PubMed1994

Oxytocin induces an inward current in pregnant rat myometrial cells.

The effects of oxytocin (OT) on holding current were studied in uterine smooth muscle cells freshly isolated from the longitudinal layer of 18-20 day pregnant rats, using the nystatin method of whole-cell voltage clamp. As we previously reported, the voltage-dependent Ca2+ current (L type) was partially inhibited by OT (about 30% inhibition at 1 microM). When the cells were held at the holding potential (HP) of -60 mV and the holding current was monitored, OT induced an inward current. The amplitude of this OT-induced current was 72 +/- 26 pA (n = 27). When the cell was held at more positive potentials (HP 0 or +40 mV), the OT-induced current reversed direction, becoming outward. This current usually was long lasting (74% of cells responding to OT); a transient current was observed in 26% of the cells. In the absence of either Na+ or Ca2+ in the bath solution, OT induced an inward current (at HP -60 mV). However, the OT-induced current was absent when both of these ions were omitted from the bath. These results suggest that OT induces an inward current through receptor-activated nonselective cation channels. The resulting increase of intracellular Ca2+ may contribute to the inhibition of voltage-dependent Ca2+ current produced by OT. This OT-induced current may also play an important role for membrane depolarization and accompanying contraction produced by OT in pregnant rat myometrium.

Animals↗
PubMed1994

Protein kinase C stimulates Ca2+ current in pregnant rat myometrial cells.

The factors that regulate the voltage-dependent Ca2+ channels in pregnant uterine smooth muscle cells have not been elucidated, including any roles for protein kinase C (PKC). Therefore, the role of PKC in the regulation of the slow (L type) Ca2+ channels was examined in myometrial cells isolated from late pregnant (18-19 day) rat uterus, using the nystatin-perforated whole-cell voltage clamp. A PKC activator, phorbol 12,13-dibutyrate (PDB), increased the L-type Ca2+ current (ICa(L)). Bath application of PDB (0.03 and 0.3 microM) increased the peak amplitude of ICa(L) by 21 +/- 14% (n = 6) and 37 +/- 8% (n = 9, p < 0.01), respectively. PDB did not change the holding current or shift the current-voltage relationship for ICa(L). The PKC inhibitors, H-7 (20 microM) or staurosporine (10 nM), reversed the effect of PDB. These results indicate that PKC may play a role in regulating Ca2+ channel function in pregnant rat myometrial cells and, therefore, may be involved in control of uterine contraction.

Animals↗
PubMed1994

Wnt-1-dependent regulation of local E-cadherin and alpha N-catenin expression in the embryonic mouse brain.

E-cadherin is transiently expressed in local regions of the embryonic mouse brain, which include several patchy areas on the mesencephalon and diencephalon and their roof plate and part of cerebellar rudiments. In the present study, we compared this E-cadherin expression with that of Wnt-1, which occurs in specific zones in the embryonic brain, and found certain spatiotemporal relations between them: Wnt-1 expression tended to run parallel or overlap with peripheries of the E-cadherin-positive areas. For example, in the dorsal midline, Wnt-1 was expressed at the middle of the roof plate, while E-cadherin was absent in the middle zone but detected in two arrays of marginal roof plate cells. Furthermore, alpha N-catenin, a cadherin-associated protein, was found to occur at the roof plate of the mesencephalon and diencephalon, coinciding with Wnt-1 expression. The expression of these molecules was then studied in two alleles of the Wnt-1 mutation, Wnt-1sw and Wnt-1neo. In mice homozygous for these mutant genes, E-cadherin expression in the roof plate was up-regulated; the middle E-cadherin-negative zone disappeared. Moreover, E-cadherin expression in the roof plate began earlier in the mutant mice than in wild-type mice. On the contrary, alpha N-catenin expression in the dorsal midline was suppressed in these mutants. These changes in cadherin and catenin expression occurred at the level of mRNA expression. These results suggest that the Wnt-1 signal is, either directly or indirectly, involved in the regulation of expression of E-cadherin and alpha N-catenin in restricted regions of the embryonic brain. This mechanism may contribute to the patterning of the expression of these adhesion-related proteins in the embryonic brain.

Alleles↗
PubMed1994

Effects of restraint stress on luteal function in rats during mid-pregnancy.

This study was undertaken to investigate the relationship between the inhibitory effect of restraint stress and the protective effect of the feto-placental luteotrophic factors on luteal function during mid-pregnancy in rats. The number of conceptuses was adjusted to one (1C group) or more than ten (FC group) on day 7 of pregnancy, and each rat received restraint stress from day 12 to day 17 of pregnancy. Restraint stress consisted of placing a rat individually in a small plastic holder three times a day for 1 h each time. Restraint stress significantly decreased serum progesterone concentration on day 17 of pregnancy in the 1C group, but not in the FC group. Restraint stress also decreased serum progesterone concentration on day 17 of pregnancy in the 1C group which received bilateral adrenalectomy on day 12 of pregnancy. The number of animals with fetal resorption in this group of rats (10 out of 14 animals) was significantly greater than in any other group of rats. The number of animals with fetal resorption in the adrenalectomized 1C group was significantly lower after daily injections of 4 mg progesterone from day 12 to day 17 of pregnancy. In the FC group of rats, even in adrenalectomized rats, restraint stress did not cause any changes in serum progesterone concentration or fetal loss. These data indicate that restraint stress is luteolytic and causes fetal loss during mid-pregnancy; this effect can be blocked by some factors from conceptuses, as occurred in the FC group.

Adrenalectomy↗
PubMed1994

Fine structure of the vomeronasal organ in the chinchilla (Chinchilla laniger).

Fine structure of the vomeronasal organ (VNO) was examined in the chinchilla (Chinchilla laniger) from a viewpoint of comparative anatomy. The VNO of chinchilla was a pair of tubular structure, about 6mm in length, and situated bilaterally along the base of the nasal septum. The VNO was encircled rostrally by the vomeronasal cartilage, but caudally by a bony capsule. The VNO communicated with the nasal cavity via a small pore at its rostral end, while it ended blindly at its caudal end. Its lumen was crescent to elliptical in a transverse plane, and lined medially with the vomeronasal sensory epithelium (VSE), but laterally with the vomeronasal respiratory epithelium (VRE). Jacobson's glands were tubulo-alveolar in type and distributed from the dorsolateral to the ventrolateral region of the VNO and opened with the duct to the lumen in the transitional region from the VSE to the VRE. Their secretions were periodic acid-Schiff (PAS)-positive but alcian blue (AB)-negative. The VSE consisted of sensory, supporting and basal cells. Supporting cells were characteristic of a large number of huge dense bodies in the perinuclear cytoplasm. The other ultrastructural features in sensory, supporting and basal cells of the VSE were similar to those in the previous reports. The VRE consisted of ciliated, non-ciliated and basal cells. Acinar cells of Jacobson's gland possessed two types of secretory granules. Secretory granules of one type were homogeneous and electronlucent, about 1,700nm in diameter, while granules of the other type were about 2,200nm in diameter, and various in electron density. The present findings suggest that the VNO is functionally active in the chinchilla.

Animals↗