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Biomedical subjects

K Shimamura

Publications and source records attributed to K Shimamura.

At least 127 records · Page 7Linked to original sources

Comparison of endothelium-dependent and -independent tension oscillation in aortae of stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats.

Differences in noradrenaline-induced tension oscillations between aortae from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control Wistar Kyoto rats (WKY) were studied. Endothelium-intact and -removed ring preparations were made from thoracic aorta of SHRSP and WKY, and isometric contraction was observed. Endothelium-intact preparations from WKY showed tension oscillations in response to high concentration of noradrenaline at significantly higher ratio, while only a few endothelium-removed preparation showed tension oscillations in response to low concentration of the drug. Fifteen out of 41 endothelium-removed preparations from SHRSP showed tension oscillations in response to low concentration of noradrenaline but no preparation showed oscillations in response to high concentration of the drug. Seven and 14 out of 42 endothelium-intact preparations from SHRSP showed oscillatory response to low and high concentration of the drug, respectively. Acetylcholine-induced relaxation and tension oscillations, both of which being significantly less in the preparation from SHRSP. Both the endothelium-independent tension oscillations and endothelium-dependent tension oscillations were abolished by removal of extracellular Ca or by verapamil. It is suggested that aortic smooth muscle of SHRSP possesses the property which produced tension oscillations, while the tension oscillations of WKY aorta is endothelium-dependent. The opening of voltage-dependent Ca++ channel of smooth muscle cell membrane which generates rhythmic contraction is increased in the aorta of SHRSP, while the release of endothelium-derived factors which induces rhythmic activities of smooth muscle cell is decreased.

Animals↗

Pulmonary fibrosis with megakaryocytoid cell infiltration and chronic myelogenous leukemia.

The relationship between fibrosis and megakaryocytic infiltration in the lungs of patients with Philadelphia-chromosome (Ph1)-positive chronic myelogenous leukemia (CML) is the focus of this review. Ph1-positive megakaryocytes are thought to reach and accumulate in the pulmonary vasculature through the marrow-blood barrier. In 21 autopsied patients with accelerated phase or blastic crisis of CML, megakaryocytic infiltration to the lungs was demonstrated in 10 patients, myelofibrosis in 12 patients and both in 5 patients. In 2 of the 10 patients with increased megakaryocytes in the lungs, relatively new fibrosis and alveolar damage in the acute phase were demonstrated with the simultaneous occurrence of myelofibrosis-"myelopulmonary fibrosis."Leakage of mitogenic factors resulting from an abnormality in the packaging mechanism of alpha-granules in these cells termed acquired grey platelet syndrome could cause fibrosis in the lungs as well as the bone marrow.

Humans↗

Forskolin inhibition of K+ current in pregnant rat uterine smooth muscle cells.

Two kinds of outward K+ currents were examined in single smooth muscle cells from pregnant rat uterus, using whole-cell voltage clamp. The first and faster component was more sensitive to 4-aminopyridine (4-AP), whereas the second and slower (delayed) component was more sensitive to tetraethylammonium (TEA). A possible third K+ component (Ca activated K+ current) was not recorded as the pipette solution included EGTA. Forskolin inhibited the outward current in a concentration-dependent manner (50% inhibition occurred at about 30 microM); it affected the delayed component rather than the fast component. 8-Bromo-cAMP did not alter the outward current. In addition, inhibitors of protein kinase A and GDP-beta S and GTP-gamma S did not affect the forskolin-induced inhibition. These results indicate that forskolin inhibition of the delayed component of the outward current is independent of cAMP generation in the pregnant rat myometrial cells. Therefore, forskolin seems to directly inhibit specific K+ channels, as was reported for several other cell types.

4-Aminopyridine↗

Effects of NG-nitro-L-arginine on electrical and mechanical responses to stimulation of non-adrenergic, non-cholinergic inhibitory nerves in circular muscle of the rat gastric fundus.

The effects of L-nitroarginine (L-NNA), an inhibitor of nitric oxide (NO) synthesis, on non-adrenergic, non-cholinergic inhibitory transmission in the circular smooth muscle of the rat gastric fundus were studied. The relaxation in response to nerve stimulation in the presence of guanethidine and atropine was depressed by the application of L-NNA (10(-4) M), and the depression was reversed by the addition of L-arginine (10(-4) M). The time course of the relaxation was altered from a monophasic to biphasic one, both of which were depressed. Stimulation of non-adrenergic, non-cholinergic nerves initiated inhibitory junctional potentials (i.j.p.). In addition, slow after-hyperpolarization was observed when stimuli were applied repeatedly at frequencies higher than 0.5 Hz. L-NNA reduced the i.j.p. partially and abolished the after-hyperpolarization, indicating the partial involvement of NO in non-adrenergic, non-cholinergic inhibitory transmission. The effects of L-NNA on the nerve-mediated relaxation are thought to be due to changes in the i.j.p. and slow after-hyperpolarization.

Animals↗

Proliferative activity of gastric cancer assessed by immunostaining for proliferating cell nuclear antigen.

The growth activity of 107 gastric carcinomas was assessed by immunohistochemical staining for formalin-fixed, paraffin-embedded tissue with a monoclonal antibody against proliferating cell nuclear antigen (PCNA). When the tumor doubling times (Tds) of 10 patients were estimated from the serum levels of carcinoembryonic antigen and carbohydrate antigen 19-9, there was an inverse correlation between the Tds and PCNA labeling index (LI) at P = 0.055. Flow-cytometric analysis was carried out by double staining for PCNA and DNA using fresh materials from 14 patients. The PCNA-positive cell fraction revealed by flow cytometry showed a good linear correlation with PCNA LI in routinely stained tissue. The LI of well-differentiated adenocarcinoma was significantly higher than that of the poorly differentiated type. When the LI was analyzed in well- or poorly differentiated adenocarcinoma, the value was significantly higher in the well-differentiated type with hepatic metastasis and in the poorly differentiated type with lymph node metastasis.

Adenocarcinoma↗

Urinary bladder carcinoma producing granulocyte colony stimulating factor (G-CSF): a case report with immunohistochemistry.

A rare case of urinary bladder carcinoma with granulocyte colony stimulating factor (G-CSF) production was reported. In an 83-year-old female, marked neutrophilia in the peripheral blood decreased from 132,500/mm3 to 3,300/mm3 after tumour resection. The tumour was a transitional cell carcinoma. The serum G-CSF level reduced from 238 pg/ml pre-operatively to normal (60 pg/ml) after the operation. Immunohistochemical investigation of the resected tumour with monoclonal antibody specific for G-CSF revealed positive staining in the carcinoma cells, confirming G-CSF secretion.

Aged↗

Autonomous production of granulocyte-colony stimulating factor in tumour xenografts associated with leukocytosis.

Leukocytosis sometimes accompanies malignant neoplasms in the absence of infection. It is thought that the production of colony-stimulating factor by neoplasms is the most potent cause of tumour-induced leukocytosis; several mechanisms have been suggested to explain this. We examined 155 human tumour xenografts established in nude mice, and found that 17 of the xenografts induced remarkable leukocytosis (> 15,000 microliters-1) in nude rats. We examined granulocyte colony-stimulating factor (G-CSF) production by the xenografts to study the mechanisms underlying this tumour-induced leukocytosis. Ten of the 17 xenografted human tumours appeared to express the G-CSF gene. Serum G-CSF increased, to concentrations of 179-37,218 pg ml-1, in host animals transplanted with the ten xenografts expressing the G-CSF gene transcripts. The biological activity of serum G-CSF also increased, to concentrations of 206-9,074 pg ml-1, in the host animals transplanted with the ten xenografts. Immunohistochemical analysis demonstrated G-CSF production at the cellular level in three of the ten xenografts. These results suggested that the production of G-CSF is a common event in human tumour xenografts associated with leukocytosis, but that factors other than G-CSF are also likely to be involved. Leukocytosis induced by neoplasms seems to be a heterogeneous and complex disorder.

Animals↗

Pulmonary fibrosis with megakaryocytoid cell infiltration in accelerated phase of chronic myelogenous leukaemia.

We report a patient in the accelerated phase of Philadelphia-chromosome-positive chronic myelogenous leukaemia who developed fibrosis in lungs, spleen and bone marrow. In the lungs, fibrosis was demonstrated in the alveolar septa which had been infiltrated by giant, bizarre-shaped cells resembling the megakaryocytes in the bone marrow. The relationship between the fibrosis and megakaryocytoid cell infiltration in the lungs is discussed.

Bone Marrow↗

Role of x-linked immunodeficiency (xid) and NK activity in rejection of human tumor xenotransplants in nude mice.

In order to elucidate the factors influencing the takes of human tumor xenografts in nude mice, we compared the transplantability of human tumors in nude mice with additional genetic defects in the immune system. The nude mice strains tested were classified as follows by expression of the beige gene and the x-linked immunodeficiency (xid) gene: 1) high NK nude (C57BL/6N, nu/nu), 2) low NK nude (C57BL/6 bg/bg nu/nu), 3) high NK nude with B-cell defect (CBA/N nu/nu), and 4) low NK nude with B-cell defect (NIH(S)III). Takes of human tumor xenografts including gastric carcinoma, T-cell lymphoma and B-cell lymphoma were better in nude mice with xid (CBA/N and NIH(S) III nude mice) than in nude mice without xid (B6 and beige nude mice). In addition, among the nude mice with xid expression, the takes were slightly better in nude mice with a CBA/N background than in those with a NIH(S) background. Moreover, the xenotransplantation rate in (CBA/N x C57BL/6N)F1 male nude mice with xid expression was higher than in (C57BL/6N x CBA/N)F1 males without xid expression, but did not react the same level as that in CBA/N nude. On the other hand, introduction of the beige gene into nude mice minimally improved the takes of human tumor xenografts under limited experimental conditions (inoculation of 100 x 10(5) T-cell lymphoma and 1 x 10(5) gastric carcinoma cells) despite the reduction of NK activity. In xenotransplantation of human tumors directly from patients, the take rates of the tumors were also better in CBA/N nude mice than in BALB/cA nude mice. The results in the present report confirmed the effect of xid and CBA/N genetic background on human tumor xenografts in nude mice, suggesting the existence of serum factors, possibly present in serum IgM, mediating rejection of the xenografts.

Animals↗

[Fine structure of the vomeronasal organ in the house musk shrew (Suncus murinus)].

Fine structure of the vomeronasal organ (VNO) was examined in an insectivore, house musk shrew (Suncus murinus), from a viewpoint of comparative anatomy. The VNO was a pair of tubular structure, about 6mm in length, and situated at the base of the nasal septum. The medial wall of the lumen of the VNO was lined with the sensory epithelium (SE) consisting of sensory, supporting and basal cells, while the respiratory epithelium (RE) lining the lateral wall was pseudostratified and covered with microvilli. Jacobson's glands were distributed on the dorsolateral to ventrolateral side of the VNO and opened to the lumen in the transitional region from the RE to the SE. Their secretion was PAS-positive bu talcian blue-negative. Ultrastructurally, sensory cells of the SE were bipolar neurons and covered on their free surface with conspicuously long microvilli. The other ultrastructural features in sensory, supporting and basal cells were similar to those in previously reported species. The ultrastructural features of the RE were also similar to those in previous reports except that the free surface was covered with microvilli instead of cilia. In addition, a few kinds of migrating cells were often observed in both the SE and the RE. Acinar cells of Jacobson's glands possessed a round to elliptical nucleus and many large secretory granules, about 1,000 nm in diameter. Rough endoplasmic reticulum and Golgi apparatus were well developed in their cytoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Relationship between blood pressure and smooth muscle tone in aortae of hypertensive rats: roles of [Ca2+].

Spontaneously developed tension (active tone) and intracellular Ca2+ level of aortae from spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), malignant SHRSP (M-SHRSP) and control Wistar Kyoto rats (WKY) were compared. Systolic blood pressure of WKY, SHR, SHRSP and M-SHRSP was 130 mmHg, 200 mmHg, 250 mmHg and 260 mmHg, respectively. Preparations from all strains of spontaneously hypertensive rats exhibited active tone which was abolished by the removal of extracellular Ca2+ or by the application of verapamil. The active tone was greater in the order of aortae from SHR < SHRSP < M-SHRSP. Intracellular Ca2+ level measured by Fura-2 method decreased by the removal of extracellular Ca2+. The degree of the decrease was greater as the blood pressure of the rats increased, indicating the greater elevation of intracellular Ca2+ level in the pressure of extracellular Ca2+. A correlation was obtained between the active tone, intracellular Ca2+ level and blood pressure. Thus, it was demonstrated that the development of the active tone is brought about by the changes in Ca2+ influx of smooth muscle cell membrane and the degree of the change is positively related to the degree of hypertension.

Animals↗

Dynamic control of cell-cell adhesion for multicellular organization.

Cadherin cell-cell adhesion molecules are associated with cytoskeletal proteins, including alpha and beta catenin, and plakoglobin. This cadherin-catenin complex plays an indispensable role in construction of ordered multicellular structures such as polarized epithelium. alpha-catenin is crucial for the cell binding function of cadherins; without it, cells cannot use the cadherin adhesion system for their adhesion. beta-catenin and plakoglobin possibly play more regulatory roles, as it was shown that their tyrosine phosphorylation correlated with modified cadherin activities. The expression of some cadherin-associated proteins is controlled by the wingless/Wnt-1 signal in embryos. These regulatory mechanisms of cadherin function and expression may be involved in dynamic control of cell-cell contacts during morphogenesis, and even in certain processes of cell growth and differentiation.

Animals↗

[A case of squamous cell carcinoma of the trachea in a female cigarette smoker].

A rare case of squamous cell carcinoma of the trachea in a female cigarette smoker is reported. The patient was a 72-year-old female with smoking index of 440 who developed wheezing and dyspnea on December 18, 1991. She was diagnosed as having bronchial asthma and hospitalized, but the symptoms were not improved. Bronchofiberscopic examination was performed and revealed a tracheal tumor on April 24, 1992. She was then referred to this cancer center. CT scan of the neck on admission showed a solid tumor which was 19 x 18 mm in diameter and protruded from the membranous portion and the right side of the tracheal wall into the lumen. Bronchofiberscopic findings revealed a soft polypoid tumor with a whitish coat on the surface and a tendency to bleed, at the second tracheal ring from the vocal cord. Histological findings of the biopsied specimen were compatible with poorly differentiated squamous cell carcinoma. A segmental resection of the trachea with end-to-end anastomosis was performed on May 6th, 1992. Postoperative radiation therapy (50.4 Gy) was added because of the residual microscopic cancer in the distal membranous portion of the tracheal wall. Female cases of squamous cell carcinoma of the trachea have been rarely reported in Japan. The relationship between squamous cell carcinoma of the trachea and smoking is considered.

Aged↗

Invasive thymoma with intracaval growth into the right atrium.

We report an unusual case of invasive thymoma with intracaval growth into the right atrium. Computed tomography and venacavography demonstrated this manner of extension of thymoma. The tumor was completely removed by means of cardiopulmonary bypass after four courses of chemotherapy. Multidisciplinary treatment for invasive thymoma with this growth pattern is thought to be useful.

Aged↗

E-cadherin expression in a particular subset of sensory neurons.

We found that the dorsal root ganglia (DRG) and trigeminal ganglia of mouse embryos express the E-cadherin cell-cell adhesion molecule and analyzed its expression profile. E-cadherin expression began around Embryonic Day 12 (E12) in these ganglia, thereafter increased, and persisted to the adult stage. This cadherin was expressed by 10 and 30% of DRG neurons in E17 and postnatal animals, respectively, as well as by satellite cells and some Schwann cells. E-cadherin-positive primary sensory fibers terminated only in a narrow region of the dorsal horn of the spinal cord, which was identified as part of lamina II by double-staining for E-cadherin and substance P or somatostatin. This E-cadherin expressing area of the spinal cord extended to part of the trigeminal nucleus in the medulla. These results showed that E-cadherin is expressed in a particular subset of primary sensory neurons which may have specific functional properties. We suggest that this adhesion molecule may play a role in the selective adhesion of sensory neuronal fibers.

Animals↗

Effects of chronic treatment with SQ29852 on spontaneous smooth muscle tone and endothelium-dependent relaxation in aorta of stroke-prone spontaneously hypertensive rats.

The effects of chronic treatment with SQ29852, an angiotensin-converting enzyme inhibitor, on spontaneous smooth muscle tone and endothelium-dependent relaxation of aorta from stroke-prone spontaneously hypertensive rats (SHRSP) were studied and compared with those of captopril. Endothelium-removed aorta from 16-week-old SHRSP exhibited a high amplitude of spontaneously developed active tension (active tone), whereas no active tone was observed in the preparation from control normotensive Wistar-Kyoto (WKY) rats. Treatment with SQ29852 or captopril at age 5-16 weeks prevented the development of hypertension. No active tone could be detected in the preparation from SQ29852-treated SHRSP. Endothelium-dependent relaxation was markedly reduced in the preparation from nontreated SHRSP compared with WKY rats. Treatment with SQ29852 prevented the impairment of endothelium-dependent relaxation. It was also shown that norepinephrine-induced contraction was markedly depressed in endothelium-intact aorta from SQ29852-treated rats. The effects of SQ29852 were more prominent than those of hydralazine when blood pressure was maintained at similar levels. It was suggested that SQ29852 exerts an action on both vascular smooth muscle and endothelium that is mediated by the inhibition of angiotension-converting enzyme in addition to indirect actions of SQ29852 that are brought about by blood pressure lowering.

Acetylcholine↗

Oxytocin actions on voltage-dependent ionic channels in pregnant rat uterine smooth muscle cells.

The effects of oxytocin, a uterotonic polypeptide hormone, on the voltage-dependent slow calcium, fast sodium, and potassium channel currents were studied using whole-cell voltage clamp of freshly isolated cells from late pregnant (18-21 day) rat myometrium. The calcium current was rapidly inhibited by oxytocin (about 25% inhibition at 20 nM) in a dose-dependent manner, and this inhibitory effect was completely reversible by washout. However, inhibition was not observed when barium was used as the charge carrier. Sodium current and potassium current were not modified by oxytocin, thus sodium and potassium currents may not play important roles in oxytocin-induced augmentation of uterine contraction. It is concluded that oxytocin stimulates uterine contraction by mechanisms other than augmentation of the voltage-dependent calcium current, e.g., by release of Ca from sarcoplasmic reticulum (by inositol triphosphate) or by activation of a receptor-operated Ca channel. The inhibition of the slow calcium current may be induced by the elevation of [Ca]i.

Animals↗