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Biomedical subjects

T Hiruma

Publications and source records attributed to T Hiruma.

31 records · Page 2Linked to original sources

Inhibitory effect of cilnidipine on pressor response to acute cold stress in spontaneously hypertensive rats.

We investigated the effect of cilnidipine on cardiovascular and neuroendocrine responses to acute cold stress in conscious and unrestrained or moderately restrained spontaneously hypertensive rats (SHRs). Acute cold stress significantly increased mean blood pressure without marked change in heart rate. The acute cold stress-induced elevation in blood pressure was almost abolished by 1 mg/kg, p.o. of prazosin. The cold stress also elevated plasma norepinephrine and epinephrine levels. Cilnidipine at 3 mg/kg, p.o. significantly inhibited the pressor response to acute cold stress. Although 3 mg/kg, p.o. of nifedipine, nicardipine or manidipine lowered mean blood pressure to a similar extent as cilnidipine, none of these three drugs affected the pressor response. Cilnidipine also reduced the cold stress-induced increment in plasma norepinephrine but not the epinephrine level. These findings suggest that acute cold stress may induce the elevation in blood pressure due to an enhanced activation of the sympathoadrenal system in SHRs and that cilnidipine may suppress the pressor response by inhibiting the sympathetic nerve activity.

Animals↗

Inhibitory effect of cilnidipine on vascular sympathetic neurotransmission and subsequent vasoconstriction in spontaneously hypertensive rats.

We reported previously that cilnidipine inhibited increases in blood pressure and plasma norepinephrine (NE) level in response to cold stress in spontaneously hypertensive rats (SHRs). In the present study, we investigated the effect of cilnidipine on sympathetic neurotransmission and subsequent vasoconstriction in SHRs. In pithed SHRs, electrical sympathetic nerve stimulation (ESNS) elevated blood pressure, and this pressor response was abolished by guanethidine. Cilnidipine at 10 micrograms/kg, i.v. and phentolamine at 1 mg/kg, i.v. suppressed the pressor response to ESNS by 28 +/- 6% and 67 +/- 3%, respectively. Neither nifedipine nor nicardipine inhibited it. The pressor response to exogenous NE was not influenced by cilnidipine. alpha, beta-Methylene ATP inhibited the pressor response to ESNS in the presence or absence of phentolamine. Cilnidipine also attenuated the phentolamine-resistant pressor response to ESNS. In SHR mesenteric vasculatures preloaded with [3H]-NE, cilnidipine (10(-7) M) as well as omega-conotoxin significantly inhibited the 3H overflow evoked by periarterial nerve stimulation. In radioligand binding experiments, cilnidipine inhibited [125I]-omega-conotoxin binding to rat synaptosomes, but it did not inhibit [3H]-prazosin binding to rat cortex membranes. These results suggest that cilnidipine may reduce electrically stimulated NE release from the sympathetic nerve endings of SHR vasculatures probably through its N-type Ca channel blocking action and that cilnidipine may also inhibit the vasoconstriction induced by ATP released concomitantly during nerve stimulation.

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Calcium-containing vacuolated mitochondria during early heart development in chick embryos as demonstrated by cytochemistry and X-ray microanalysis.

The ultrastructure of mitochondria in the developing heart was examined in chick embryos from 2 to 7 days after fertilization. Vacuolated mitochondria were observed in the heart muscle cells of embryos at all stages examined. The number of vacuolated mitochondria as a percentage of total mitochondria in muscle cells was high in embryos at 3 and 4 days and was much higher in the ventricular cells than in the atrial cells. Examination by cytochemistry and X-ray microanalysis revealed the accumulation of calcium in the vacuoles of mitochondria. These results suggest important roles for vacuolated mitochondria in the regulation of the intracellular concentration of calcium during the early development of the chick heart.

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[Osteolytic and osteosclerotic lesion of the femur associated with pustulosis palmaris plantaris].

The cases with pustulosis palmaris et plantaris associated with lesions in sterno-cost clavicular region, spine and ilio sacral joint have been in the previous literatures. We encountered four rare cases of this pustulosis in association with femoral lesion. We mainly reported their radiological and pathologic findings. Three cases had lesions in the diaphysis of the femur, while one case had lesion in the lesser trochanter. The average age was 55.5 years (range 53-60) All patients complained of thigh pain. Three cases suffered sterno cost clavicular pain also. Laboratory data showed the elevation of white blood cell number, ESR and tested positive for C-reactive protein. The radiological findings showed osteolytic lesions of the femoral cortex at the onset of the disease, followed by thickening and sclerosis in the cortex. A biopsy was performed in three cases and the pathological results showed no malignancy. The specimens showed only chronic inflammation. Pathological results and radiological abnormalities suggested that femoral lesion of pustulosis palmaris et plantaris originated from the periostenum or the cortex of bone.

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Histogenesis of tunica media of the chick aorta.

We investigated the formation of the aortic tunica media in developing chicks from Hamburger-Hamilton stage (st) 12 to 1-day after hatching. At st 12, some cells of the lateral plate and the somite adjacent to the aorta extended processes toward the aortic endothelial tube. This is the first sign of the tunica media formation of the aorta. Then, these cells detached from the lateral plate and the somite attached to the aortic endothelial tube and covered it almost entirely by st 18. At this stage, bundles of microfilaments and spots of dense material were found in the peripheral region of cells of the tunica media (media cells); suggesting the earliest differentiation of smooth muscle cells. Subsequently, the tunica media increased in the number of cell-layers, reaching approximately 20 layers at st 34 (8-day incubation). The outer layers of the tunica media consisted of undifferentiated cells, whereas typical smooth muscle cells were found within the inner 4 to 5 layers. Elastic fibers first appeared at this st 34. With there was an increase in the elastic component, the tunica media assumed the lamella structure consisting of the alternating myocytes and elastic laminae. The aortic media 1-day after hatching essentially exhibited the same mature state as seen in the adult chickens.

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[Rabbit osteosarcoma induced by hydroxypropylcellulose mixed beryllium oxide pellet--comparison between implantations into bone marrow cavity and into fracture callus of the femur].

Hydroxypropylcellulose mixed beryllium oxide pellets were implanted into the distal metaphysis in the right femurs of 30 rabbits (3 groups, 10 rabbits each): in Group 1 into the internal callus 1 week after production of artificial fracture at a dose of 300 mg, in Group 2 into the bone marrow cavity at a dose of 300 mg, and in Group 3 into the bone marrow cavity at a dose of 50 mg. Osteosarcoma was induced in all of 10 rabbits in Group 1, 7 out of 10 in Group 2, 1 out of 10 in Group 3 at 56 weeks after implantation of BeO. In Group 1, the emergence of tumor and the increase of serum alkaline phosphatase appeared significantly earlier and 80% of the animals with osteosarcoma showed lung metastasis. This experimental method, especially that used in group 1, appears to be useful for the study of human osteosarcoma.

Alkaline Phosphatase↗

Epicardial formation in embryonic chick heart: computer-aided reconstruction, scanning, and transmission electron microscopic studies.

Epicardial formation in the embryonic chick heart from initial to final stages was revealed by means of computer-aided reconstructions based on serial resin sections for light microscopy, with further detailed observations using scanning and transmission electron microscopy. The origin of the epicardium was recognized as protrusions of mesothelial cell clusters on the right side of the external surface of the sinus venosus at 23 somites (stage 14+). These protrusions elongated to give rise to several villous processes, the tips of which eventually touched the dorsal wall of the embryonic heart at 30 somites (stage 17). Originating from these adhesion sites, mesothelial cells spread gradually onto myocardial cells in all directions to form a monolayered sheetlike cover. Thus, by stage 23, the ventricle was completely overlaid with epicardium, and blood-island-like structures appeared within the subepicardial layer. The atrium was not enveloped by epicardium until stage 25, and the extreme distal end of the bulbus cordis was reached by the advancing epicardium at stage 27. A chronological table of epicardial formation in the chick heart is presented.

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Early cardiogenesis in the newt embryo.

The migration of cardiogenic cells and the formation of a tubular heart in newt embryos were examined mainly by scanning electron microscopy (SEM). Cardiogenic cells are known to localize at the border region of lateral mesoderm migrating in the space between the ectoderm and the endoderm. They initially (before stage 20 or mid-neurula) appeared to attach to the basal surface of the ectoderm, whereas later (after stage 22 or late neurula) they changed their scaffold to the endoderm. On the scaffold cell surface, very fine fibrils of extracellular matrix (ECM) were found. These fibrils were proved to be composed partly of fibronectin by the immunofluorescence method as well as by immunoSEM using latex bead-labeled antibody, suggesting their seemingly important role in migration of cardiogenic cells. At stage 26 or the early tail bud stage, when the tips of bilateral cardiogenic areas begin to fuse under the foregut, several free vasoformative cells are seen there and the mesodermal sheet itself splits into two layers to produce a coelomic cavity. The splanchnic wall of the coelomic or pericardial cavity was recognized to form a though consisting of cobblestone-like myocardial cells not yet covered with the epicardium.

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An ultrastructural topographical study on myofibrillogenesis in the heart of the chick embryo during pulsation onset period.

Ultrathin sections of the chick embryonic heart at the 8-, 9- and 10-somite stage were cut serially at an interval of 20 micron and mounted for transmission electron microscopic examination on a copper grid with a sufficiently large hole to survey the entire section area. The grid was supported by a formvar film. Thick filaments were first found to assemble into well-defined bundles in several cells composing the caudal region of the newly formed heart just before onset of the pulsation at the 8-somite stage. Then, at the 9-somite stage when pulsation commences, the cells possessing nascent myofibril(s) increase in number, slightly more in the right side of ventricular region. At the 10-somite stage, the rhythmical contraction is established and striated myofibrils become distinctly discernible. Right side dominance is more conspicuous at this stage than previously. Then, myofibrillogenesis gradually progresses toward the cranial or bulbar region.

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TEM-studies on development and canalization of the dorsal aorta in the chick embryo.

Transmission electron microscopic investigations were carried out on the early development of the dorsal aorta in chick embryos during the period ranging from the 6-somite stage to the 16-somite stage. Special attention was paid to the formation of the vascular lumen. The initial angioblasts tended to aggregate into a cluster with a narrow intercellular space. Only a few punctate thickenings of the plasma membrane were found at junctional sites of the angioblasts. The vascular cavity appeared to be produced by expansion of the intercellular space and possibly also by enclosure of the extracellular space with attenuated vasoformative cells. The wall of the early vessels so formed was frequently observed to be open to the extravascular space through clefts originating probably from incomplete closure of the early endothelium. No specific ultrastructural features characterizing the angioblasts or early endothelial cells were recognized.

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Scanning electron microscopic study on the development of primitive blood vessels in chick embryos at the early somite-stage.

Primary vasculogenesis in chick embryos at the early somite stage (1-14 somites) was investigated mainly by scanning electron microscopy (SEM), with special reference to the development of primitive blood vessels such as the arteria et vena vitellina (AV, VV), aorta dorsalis (AD) and vena cardinalis (VC). After glutaraldehyde fixation, the endoderm or ectoderm was removed from the embryos to expose either the ventral (AV, VV, AD) or the dorsal (VC), vascular system. The mode of vascular formation was found to be identical in all these blood vessels, arising first in loco as isolated solid masses or cords composed of so-called angioblasts. The angioblasts at this developmental phase could be distinguished from underlying mesenchymal cells, exhibiting a relatively flat surface. The VV was recognized first on both sides of the anterior intestinal portal at the 4-somite stage, whereas the forming AD was identified on the ventral surface of the paired somites at the 6-somite stage, appearing almost simultaneously from the cranial to caudal somite regions. After the 8-somite stage, the AV was formed by transformation of one of the caudal plexuses spreading to the area vasculosa. In the 9-somite stage, the angioblastic cords of the VC appeared on the dorsal side of the mesoderm in the same manner as for other ventral vessels. This finding differs from the statement of a previous author that the VCis formed by longitudinal anastomosis of intersegmental diverticula of the AD.

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