Biomedical subjects

S Hamano

Publications and source records attributed to S Hamano.

At least 91 records · Page 5Linked to original sources

PubMed1996

Inhibitory effects of tranilast on proliferation, migration, and collagen synthesis of human vascular smooth muscle cells.

The aim of this study was to examine the effects of tranilast (anti-allergic drug) on proliferation, migration, and collagen synthesis in cultures of human vascular smooth muscle cells. Tranilast at 100 and 300 microM had several inhibitory effects. One is the effect on vascular smooth muscle cell proliferation induced by fetal bovine serum and platelet-derived growth factor (PDGF)-BB. Second is the effect on PDGF-BB-induced migration. Third is the effect on c-myc expression after PDGF-BB stimulation. Lastly, tranilast reduced the spontaneous collagen synthesis without reducing total protein synthesis. These results suggest that tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty via the inhibitory effects on proliferation, migration, c-myc gene expression, and collagen synthesis of vascular smooth muscle cells.

Anti-Allergic Agents↗

PubMed1995

Effects of low molecular weight heparin on a severely antithrombin III-decreased disseminated intravascular coagulation model in rabbits.

The effect of dalteparin, a low molecular weight heparin, on severely antithrombin III (ATIII)-decreased disseminated intravascular coagulation (DIC) model was compared with that of unfractionated heparin (heparin). The DIC model in rabbits was produced by continuous infusion of thrombin in combination with bolus injection of latex. After a 3 hr infusion of thrombin, plasma ATIII activity was lowered to 30% of normal plasma. Platelet number, fibrinogen content and alpha 2 plasmin inhibitor (alpha 2PI) activity were also decreased. Dalteparin (25-100 IU/kg/hr) and heparin (25-100 U/kg/hr) inhibited the decrease in ATIII activity, platelet number and fibrinogen content, and had no effect on alpha 2PI activity. Activated partial thromboplastin time (APTT) was prolonged by heparin (50 and 100 U/kg/hr), but not by dalteparin (25-100 IU/kg/hr). The ratio of anti-factor Xa (F.Xa) activity to anti-thrombin activity for dalteparin (50 IU/kg/hr) was higher than that for heparin (50 U/kg/hr). With the addition of exogenous ATIII, the ratio of anti-F.Xa to anti-thrombin for heparin increased, but that for dalteparin did not change. However, the increased ratio for heparin was still lower than the unchanged ratio for dalteparin. These results suggest that both dalteparin and heparin have the ability to rectify the abnormal parameters of severely ATIII-decreased DIC, and that the effects of dalteparin are mainly involved with anti-F.Xa activity whereas the effects of heparin are via anti-thrombin activity.

Animals↗

PubMed1995

Inhibition of PDGF- and TGF-beta 1-induced collagen synthesis, migration and proliferation by tranilast in vascular smooth muscle cells from spontaneously hypertensive rats.

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate faster and are more sensitive to transforming growth factor-beta 1 (TGF-beta 1) than those of normotensive Wistar-Kyoto rats. We studied the in vitro effects of tranilast, an anti-allergic drug, on the proliferation, migration and extracellular matrix synthesis in the SHR-VSMC. There were many inhibitory effects of tranilast (30-300 microM) on SHR-VSMC. One is the effect on the proliferation stimulated with fetal bovine serum (FBS), TGF-beta 1 and platelet-derived growth factor-BB (PDGF-BB). Another is the effect on the PDGF-BB-induced migration. Lastly, tranilast exhibited inhibitory effects on spontaneous collagen synthesis and TGF-beta 1-induced collagen and glycosaminoglycan synthesis. On the other hand, collagen induced the VSMC migration concentration-dependently. These results suggest that tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed1995

Muscle and intramuscular nerve pathology in congenital hypomyelination neuropathy.

Two patients had delayed development and generalized muscle hypotonia and weakness since early infancy. Their muscle biopsies showed slight variation in fiber size without group atrophy, and no clear evidence of an active demyelinating process in the intramuscular nerves. The most striking finding by light microscopy was the absence of myelinated fibers in the intramuscular nerve bundles. Ultrastructurally, the axons were devoid of myelin sheath or had very thin myelin sheaths, and the axons were surrounded by multilayered basal lamina forming an atypical onion bulb with no suggestions of myelin destruction. A sural nerve biopsy from one of the patients showed similar findings. Unlike the Déjèrine-Sottas type of hereditary motor and sensory neuropathy, there was no evidence of demyelination and remyelination in the muscle pathology, suggesting that the poor myelination in congenital hypomyelination neuropathy is due to a true "hypo"-myelination and not the result of demyelination.

Biopsy↗

PubMed1995

Paroxysmal kinesigenic choreoathetosis associated with prenatal brain damage.

We describe a 15 year old patient with paroxysmal kinesigenic choreoathetosis. Neurological examinations revealed a paresis of the right arm and hand that was similar to ulnar nerve palsy, a right homonymous hemianopsia and an ocular movement disturbance of smooth pursuit to left. Attacks of dystonic spasms began abruptly, usually following running, and lasted less than 5 min. Magnetic resonance imaging displayed a linear area of increased signal in the T2-weighted images along the lateral margin to the left putamen, atrophies of the frontal and temporal opercula and a large porencephalic cyst in the left parieto-temporo-occipital region. A cerebral blood flow study with single photon emission computed tomography showed hypoperfusion of the lenticular nucleus and the regions corresponding to the atrophies and the porencephalic cyst. Electroencephalograms during the attacks could not demonstrate epileptic abnormality. Only the neuronal plasticity of an immature brain could explain the discrepancy between the observed huge lesions of the brain and the minor neurological symptoms present. Attacks of paroxysmal kinesigenic choreoathetosis might occur when the basal ganglia maturate to some extent, even if the lesions in the brain were caused before birth.

Adolescent↗

PubMed1995

Induction of apoptosis of T cells by infecting mice with murine cytomegalovirus.

Cytomegalovirus (CMV) is associated with several lymphocyte dysfunctions, but the precise mechanisms of the dysfunctions are still unclear. To elucidate the mechanisms, a cell cycle-DNA content analysis was performed on splenic T cells of murine CMV (MCMV)-infected BALB/c mice. T cells from mice infected with 3 x 10(3) PFU of MCMV contained a higher percentage of hypodiploid nuclei after 12 or 24 h of culture than those from naive mice. T cells from infected mice also contained a larger amount of fragmented DNA. Taken together, these results suggested that infection with MCMV induced the apoptotic cell death of T cells. This induction of apoptosis accounted for the dysfunction of lymphocytes, at least partially. Flow cytometric analysis showed that T cells as well as B cells from MCMV-infected mice expressed an augmented level of Fas antigen, an apoptosis-associated cell surface molecule, which might be the cause of the apoptosis of cells. T cells from MCMV-infected C57BL/6-lpr/lpr mice with mutations at the lpr/fas locus, however, also showed a substantial level of apoptosis, which was reproducibly lower than that seen in C57BL/6 mice. Therefore, it was suggested that the Fas-mediated pathway contributed to but was not sufficient for the induction of apoptosis and that mechanisms other than the Fas-associated pathway were also involved in the induction of apoptosis.

Animals↗

PubMed1995

Saccular aneurysms of the proximal (M1) segment of the middle cerebral artery.

We report A series of 20 consecutive patients with 21 saccular aneurysms of the proximal (M1) segment of the middle cerebral artery. The incidence of M1 aneurysms was 3.0% among 660 patients with intracranial aneurysms and 12.9% among 155 patients with middle cerebral artery aneurysms in our center. Of the 20 patients, 2 were men and 18 were women. The aneurysms were classified into two types: the superior wall type (9 cases), arising at the origin of the lenticulostriate or fronto-orbital artery, and the inferior wall type (12 cases), arising at the origin of the early temporal branches. Twelve (60%) patients had ruptured M1 aneurysms. The incidence of multiple aneurysms was high (nine patients, 45%), and M1 aneurysms were responsible for subarachnoid hemorrhage in four patients. Of 14 M1 aneurysms greater than 5 mm in diameter, 11 (78.6%) ruptured. In contrast, only one (14.3%) of seven small (< or = 5 mm) aneurysms ruptured. In 12 patients with ruptured M1 aneurysms, intracerebral hematomas were recognized in 6 (50%). Intracerebral hematomas by the superior wall M1 aneurysms were located in the frontal lobe, and those by the inferior wall M1 aneurysms were in the temporal lobe. Fifteen patients (75%) made a useful recovery 6 months after surgery. Four patients (20%), who were in poor grade condition preoperatively, remained severely disabled. One patient died of sepsis 2 months after she recovered well from the operation. Special attention to the lenticulostriate arteries to avoid injury is critical for successful surgical treatment.

Adult↗

PubMed1994

Development of the human medial superior olivary nucleus: a morphometric study.

The development of the human medial superior olivary nucleus was studied in serial sections of 10 fetuses at 12-35 weeks of gestation (WG), an infant at 2 months of age and an adult of 63 years using an electronic planimeter with a computer. Morphometric analysis suggested that the development of the human medial superior olivary nucleus accelerates between 16 and 21 WG in terms of columnar lengths and volumes, neuronal sizes and circularity ratios, while it matures gradually in terms of the amount of Nissl bodies.

Female↗

PubMed1994

Characterization of the zona pellucida glycoproteins from bovine ovarian and fertilized eggs.

Bovine zona pellucida (ZP) glycoproteins from ovarian egg emerged as three bands with molecular mass of 78 kDa, 64 kDa and 21 kDa in SDS-PAGE under reducing conditions. Endo-beta-galactosidase (E beta G) digestion of the glycoproteins yielded five products with molecular mass of 76 kDa (E beta G-76), 68 kDa (E beta G-68), 63 kDa (E beta G-63), 47 kDa (E beta G-47) and 21 kDa (E beta G-21) under the same conditions. The N-terminal amino acid sequences of E beta G-76 and E beta G-21 were identical. This fact together with the results of diagonal SDS-PAGE indicated that E beta G-21 (N-terminal region) is linked to E beta G-63 (C-terminal region) through disulfide bond to form E beta G-76. Immunoblot analysis using anti-pig ZP protein antibodies revealed that bovine E beta G-76, E beta G-68 and E beta G-47 correspond to pig PZP2, PZP3 alpha and PZP3 beta glycoproteins, respectively. The E beta G-76 and E beta G-68 components were shown to be specifically cleaved during fertilization.

Amidohydrolases↗

PubMed1994

Ionic factors affecting the association of tyrosine hydroxylase with chromaffin granules in the adrenal medullary cell.

Chromaffin cells were treated with digitonin in medium containing various ions and the efflux of tyrosine hydroxylase from these permeabilized cells was then determined to elucidate a possible influence of cytoplasmic ionic environment on the association of this enzyme with the chromaffin granule. The enzyme efflux was observed with a distinct lag during exposure to low concentrations of digitonin in the medium containing isotonic sucrose. In contrast, a larger extent of the enzyme efflux was observed without any notable delay in the presence of isotonic NaCl. The results were thought to indicate the possibility that the dissociation of soluble enzyme from the granule surface within the permeabilized cells might occur in the presence of NaCl. Furthermore, the interaction between tyrosine hydroxylase and isolated chromaffin granule membranes was directly examined, and this interaction was shown to be inhibited by NaCl. However, the enzyme-granule membrane interaction was also inhibited by KCl and choline chloride. It therefore seems possible to consider that the inhibitory action of NaCl on the association of soluble enzyme with the granule may not be due to the specific action of Na+, but presumably due to the non-specific chaotropic effect of Cl-. On the other hand, the enzyme efflux was markedly reduced by the presence of Ca2+ in the permeabilizing medium, but the enzyme-granule membrane interaction was not affected by Ca2+ at the same concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

PubMed1994

Contraction and depolarization induced by fetal bovine serum in airway smooth muscle.

We investigated the effects of fetal bovine serum (FBS) on the resting membrane potential and muscle tone of canine airway smooth muscles using tension recording and microelectrode methods. At concentrations > 0.1%, FBS induced a sustained increase in muscle tone. At concentrations > 1%, FBS depolarized the resting membrane potential of dog trachea in a dose-dependent manner. When FBS was dialyzed, it failed to induce a sustained increase in muscle tone or to depolarize the membrane, indicating that FBS contained factor(s) that induced contraction of dog airway smooth muscles. When FBS was dialyzed against distilled water, the outer solution which was freeze dried and then reconstituted (> 1% in original vol) induced a sustained increase in muscle tone, indicating that FBS contained dialyzable factor(s) that increased muscle tone and depolarized the resting membrane potential of dog airway smooth muscles. Methysergide (10(-6) M) or cyproheptadine (10(-6) M), nonspecific antagonists to serotonin receptors, 5-hydroxytryptamines (5-HT1 and 5-HT2), markedly reduced the FBS-induced increase in the muscle tone to approximately 20% of the original value but did not abolish the response. On the other hand, methysergide (10(-6) M) completely suppressed the increase in the muscle tone evoked by peak fractions obtained by application of the dialysate of FBS or 5-HT to a C18 reverse-phase column, indicating the peak fractions contained only 5-HT. These observations indicate that FBS contained 5-HT and an unknown factor(s) responsible for increase in the muscle tone of the airway smooth muscle induced by FBS.

Animals↗

PubMed1994

Effects of epithelial cell supernatant on membrane potential and contraction of dog airway smooth muscles.

We investigated the effects of cultured epithelial cells and supernatants on resting membrane potential and excitatory neuroeffector transmission in smooth muscle cells of dog trachea and bronchioles. The mean resting membrane potential of the mucosa-free tracheal smooth muscle cells was -59.5 +/- 1.5 mV (+/- SD). Application of cultured epithelial cells (> 2.5 x 10(5) cells/ml) hyperpolarized the membrane, resulting in a potential of -64.5 +/- 1.7 mV. The supernatant of the cultured epithelial cells also increased the resting membrane potential of the mucosa-free tracheal smooth muscle cells by 4 to 9 mV. These hyperpolarizing actions were not modified by indomethacin (10(-5) M), l-NG-nitroarginine (10(-5) M), or oxyhemoglobin (10(-5) M), but were inhibited by glibenclamide (10(-6) M). The supernatants of the cultured epithelial cells completely or partially suppressed the contractile response of epithelium-denuded bronchioles to electrical field stimulations and suppressed the amplitude of excitatory junction potentials of the trachealis evoked by electrical field stimulations. Indomethacin prevented the inhibitory effect of supernatants on the amplitude of twitch contractions and excitatory junction potentials and markedly suppressed supernatant-associated inhibition of the excitatory neuroeffector transmission. Furthermore, indomethacin with AA861, a lipoxygenase inhibitor, completely suppressed this effect. Our findings suggest that cultured airway epithelial cells spontaneously release at least two factors. One factor selectively modulates the resting membrane potential, and the other inhibits the excitatory neuroeffector transmission.

Animals↗

PubMed1994

Ca2+ inactivation of voltage-dependent Na+ channels in cultured bovine adrenal chromaffin cells: further studies on inhibition of veratridine-induced catecholamine secretion by external Ca2+.

The stimulatory actions of veratridine (VTD) on catecholamine secretion and Na+ influx in cultured bovine adrenal chromaffin cells were studied in the presence of high concentrations of Ca2+ in the incubation mixture. Catecholamine secretion evoked by VTD was reduced by elevating the external Ca2+ concentration to higher than 2 mM. Under the same conditions, VTD-stimulated 22Na+ uptake into the cells was also reduced by elevating the extracellular Ca2+ concentration. In contrast, the secretory action of VTD was not significantly suppressed by preloading Ca2+ to the cells. Furthermore, the effects of extracellular Ca2+ on the sensitivities of the cells to VTD and tetrodotoxin (TTX) were examined, and neither their sensitivities to VTD nor those to TTX were shown to be significantly altered by elevating the Ca2+ concentration in the incubation mixture. These results seem to indicate that the elevation of extracellular Ca2+ concentration may cause the inhibition of VTD-induced catecholamine secretion as a consequence of the inactivation of voltage-dependent Na+ channels, and suggest that Ca2+ may directly act on the cell surface, and the site of Ca2+ action is presumably distinct from the sites of both VTD and TTX actions in the plasma membranes of adrenal chromaffin cells.

Adrenal Medulla↗

PubMed1994

Stimulatory effect of pituitary adenylate cyclase-activating polypeptide on catecholamine synthesis in cultured bovine adrenal chromaffin cells: involvements of tyrosine hydroxylase phosphorylation caused by Ca2+ influx and cAMP.

In cultured bovine adrenal chromaffin cells, pituitary adenylate cylase-activating polypeptide (PACAP) stimulated [14C]catecholamine synthesis from [14C]tyrosine (but not from [14C]DOPA) in a concentration-dependent manner, causing maximal stimulation at 10(-7) M. The stimulatory action of PACAP was not affected by staurosporine (an inhibitor of protein kinase C) or in the cells in which protein kinase C was down-regulated by prolonged exposure to TPA (an activator of protein kinase C), whereas it was partially attenuated in Ca(2+)-free medium. PACAP (10(-7) M) increased the formation of [3H]inositol phosphates, [Ca2+]i and 45Ca2+ uptake as well as cAMP. The peptide also stimulated the phosphorylation of tyrosine hydroxylase, the enzyme catalyzing the rate-limiting step in catecholamine synthesis. Catecholamine synthesis and tyrosine hydroxylase phosphorylation stimulated by the maximal effective concentration of dibutyryl cAMP or high K+, which activates Ca2+ uptake, were further enhanced by PACAP, suggesting that both cAMP- and Ca(2+)-dependent protein kinases may be involved in the stimulation of tyrosine hydroxylase phosphorylation and catecholamine synthesis caused by PACAP.

Adrenal Medulla↗

PubMed1994

[A case of hemimegalencephaly: ictal EEG and SPECT].

A case of 1-month-old female infant with hemimegalencephaly was reported. This disorder is a rare malformation characterized by congenital hypertrophy of one hemisphere and ipsilateral ventriculomegaly. Clinical signs of the patient included a left sided macrocephaly, intractable seizures and delayed development. Ictal single photon emission computed tomography (SPECT) on the 49th day using 99mTc-HMPAO showed hyperperfusion in the left occipital and frontal lobes, when ictal EEG showed a sharp wave-burst appearing continuously in the left occipital lobe that spread to the left frontal lobe. Interictal SPECT on the 48th day demonstrated and increased tracer accumulation in the left hemisphere, especially in the left frontal lobe. In this case, the megalencephalic hemisphere might have an important role for epileptogenesis and its spread according to the ictal SPECT findings.

Brain↗

PubMed1994

Lack of relationship between gamma-glutamyl transpeptidase and tyrosine transport in cultured bovine adrenal chromaffin cells.

Effect of gamma-glutamyl transpeptidase (GGTP) inhibitor acivicin on tyrosine transport was investigated in cultured bovine adrenal chromaffin cells. Tyrosine transport into the cells was inhibited by acivicin at the low concentration range. This drug also caused the inhibition of GGTP in the cell lysates, but the concentration required for the inhibition of the enzyme was evidently different from that producing the inhibition of tyrosine transport into the cells. In addition, tyrosine transport was not affected by a GGTP activator hippurate even at the high concentration. These results seem to provide the evidence that GGTP may not be involved in the transport of tyrosine into the adrenal chromaffin cell.

Adrenal Glands↗

PubMed1994

[Brain perfusion in acute infantile hemiplegia studied with single photon emission computed tomography].

Sequential examinations of single photon emission computed tomography (SPECT) were performed on a 5-month-old boy with acute infantile hemiplegia from the acute ictal stage. SPECT was performed with technetium-99m-hexamethyl-propylene-amineoxime during the status when the patient had left-hemiconvulsions (status epilepticus) and on the 3rd, 7th and 10th day after the status. During the ictal stage and the 3rd day after the status, diffuse hyperperfusion was revealed in the right hemisphere, while diffuse hypoperfusion was exhibited in the right hemisphere on the 7th and 10th day after the status. Hypoperfusion in the corresponding hemisphere, after the status, has been reported in patients with acute infantile hemiplegia. There has, however, been no report of ictal brain perfusion. The pathogenesis of this hyperperfusion is not clear, but alteration of brain perfusion in this patient, especially in acute phase, may help to elucidate the etiology of acute infantile hemiplegia.

Brain↗

PubMed1993

In vitro fertilization and development of bovine oocytes recovered from the ovaries of individual donors: A comparison between the cutting and aspiration method.

Bovine oocytes were recovered from ovaries by either the cutting or the aspiration method, after which the oocytes were fertilized and cultured in vitro to investigate their developmental ability. In the cutting method, the surface and the interior of ovaries were cut with a set of 10 razors stacked at 2-mm intervals in modified TCM-199 medium supplemented with 5% fetal bovine serum; the liberated oocytes were then collected. In the aspiration method all visible follicles (2 to 5 mm in diameter) at the ovarian surface were aspirated with a syringe and an 18-gauge needle. Significantly more oocytes were recovered by the cutting than the aspiration method (mean: 63.3 vs 22.1), and the proportion of Rank A oocytes was also higher for the cutting method (84.6 vs 41.3%). Although no significant differences were observed between the 2 methods in the proportion of fertilized oocytes developing to the blastocyst stage in culture, the average number of blastocysts obtained by the cutting method was about 3.6-fold higher than by aspiration. The blastocysts were transferred nonsurgically to 37 (cutting method) and 36 (aspiration method) recipients, and 22 (59.0%) and 19 (52.8%), respectively, became pregnant.

Journal Article↗