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Biomedical subjects

M Asada

Publications and source records attributed to M Asada.

At least 37 records · Page 2Linked to original sources
PubMed2001

Possible involvement of cyclic adenosine monophosphate-independent mechanism in the positive chronotropic effect of norepinephrine in the isolated guinea pig right atrium.

BACKGROUND: Although both positive chronotropic and inotropic effects of beta-adrenergic stimulation are thought to be mediated by cyclic adenosine 3'5'-monophosphate, phosphodiesterase III inhibitors such as amrinone and milrinone potentiate the positive inotropic effect of catecholamines with minimum influence on the heart rate in clinical setting. The aim of the current study was to compare the positive chronotropic effect of norepinephrine with that of forskolin to elucidate whether cyclic adenosine monophosphate is relevant to the chronotropic effect of norepinephrine. METHODS: Concentration-response curves for the positive chronotropic effects of norepinephrine and forskolin on the spontaneously beating right atria of guinea pigs were determined in the absence and presence of phosphodiesterase inhibitors or ion channel inhibitors. In some experiments, the left atria driven electrically were used to determine the positive inotropic effect of norepinephrine. RESULTS: Norepinephrine and forskolin increased the beating rate in a concentration-dependent manner. The positive chronotropic effect of forskolin was potentiated by amrinone and 3-isobutyl-1-methylxanthine, whereas the positive chronotropic effect of norepinephrine was not potentiated by the phosphodiesterase inhibitors. In contrast, the positive inotropic effect of norepinephrine was potentiated by amrinone. The hyperpolarization-activated inward current inhibitor cesium chloride and L-type voltage-dependent Ca2+ current inhibitor verapamil suppressed the chronotropic effect of norepinephrine, whereas these inhibitors did not affect the chronotropic effect of forskolin. CONCLUSION: Norepinephrine increases the spontaneously beating rate by a different mechanism from that of forskolin, suggesting that cyclic adenosine monophosphate is causally unrelated to the positive chronotropic effect of norepinephrine in the guinea pig heart.

Adrenergic alpha-Agonists↗
PubMed2001

[Approaches to sella turcica in endoscopic pituitary surgery].

Recent advances in endoscopic sinus surgery suggested the potential for its surgical application to pituitary surgery. A number of institutions have reported the advantage of endoscope use in pituitary surgery, which is now widely accepted, but approaches to the sella vary in the literature. We retrospectively studied sella approaches in endoscopic pituitary surgery as rhinologists. Subjects included 6 cases of pituitary adenoma and 2 cases of Rathke's cleft cyst. A both-nostril transnasal transsphenoidal approach, our standard technique, was used in 6 cases. This approach consisted of elevation of mucoperiosteal flaps, resection of the vomer and sphenoid anterior wall, and opening of the sellar floor. Elevated mucoperiosteal flaps were used to close of the sella after tumor resection. All tumors were removed and no significant postoperative complications occurred. We found the both-nostril transnasal approach to be easy and time-saving and provided surgeon with a broad surgical field necessary to treat large tumors and accidental cases. Postoperative observation of the sella was easy for wide opening of the anterior wall of the sphenoid sinus. In our experience with reoperation, we quickly accessed the sella and easily removed tumors in the second operation. Our technique therefore has an advance in treatment of recurrence. The both-nostril transnasal approach involves the same procedures as median drainage of the sphenoid sinus, so our technique may have advantages in preventing mucocele of the sphenoid sinus as a late complication of transsphenoidal surgery. The transnasal transsphenoidal approach via both nostrils is preferable rhinologically.

Adenoma↗
PubMed2001

[A case of suprasellar hemangioblastoma with thoracic meningioma].

Supratentorial hemangioblastoma is encountered very rarely, with only about 110 cases reported. This report concerns a case of a suprasellar hemangioblastoma associated with thoracic meningioma. A 62-year-old man was admitted with visual disturbance of the left eye. T2-weighted magnetic resonance imaging (MRI) showed a high signal intensity mass in the suprasellar region without perifocal edema. T1-weighted MRI with gadolinium showed a homogeneously enhanced mass. The angiogram revealed remarkable tumor staining originating from the right and left internal carotid arteries (ICA) and the left external carotid artery (ECA). On the basis of the pre-operative diagnosis of tuberculum sellae meningioma, total tumor removal was performed. Photomicrographs of the specimen showed numerous capillaries divided by stroma cells. Positive immunostaining for factor VIII related antigen (F VIII RAg) was observed in endothelial cells, but immunostaining for epithelial membrane antigen (EMA) was not observed in any cells. A diagnosis of suprasellar hemangioblastoma was made on the basis of these findings. The patient suffered paraparesis on the postoperative seventh day. Since MRI showed a thoracic tumor, a second total tumor removal was performed. The tumor was diagnosed as a meningothelial meningioma. The patient was discharged without evidence of new neurological deficits. Our experience shows that, when a mass is vascularized in the cerebral hemisphere, the possibility of hemangioblastoma needs to be taken into consideration.

Hemangioblastoma↗
PubMed2001

[Anesthetic management for cardioverter defibrillator implantation in a patient with preoperatively undiagnosed myotonic dystrophy].

We unexpectedly anesthetized a 31-year-old male with mild myotonic dystrophy (MD) that had not been diagnosed preoperatively, for implantable cardioverter defibrillator (ICD) implantation. Although MD is an uncommon disorder, cardiac conduction abnormalities and dilated cardiomyopathy are seen commonly in these patients. Therefore, chances of ICD implantation may increase in MD patients. But, the patients are often unaware of this disease and it is common for them to conceal their symptoms, and the diagnosis may not be made before the operation. We emphasize that preoperative assessment is important and that it is necessary to consider MD in patients for ICD implantation.

Adult↗
PubMed2000

Effect on fertilization and development by re-culture after freezing and thawing of bovine oocytes matured in vitro.

This study evaluated the effect of 6-h repeat culture before insemination of frozen-thawed, in vitro-matured oocytes on their fertilizability and developmental capacity. Immature oocytes were cultured for 18 h or 24 h and were frozen incrementally. Post-thaw oocytes were repeat cultured for 0 h (control) or 6 h before insemination. With fertilizability, the proportion of enlarged sperm head was significantly (P<0.05) higher in oocytes cultured for 24 h without repeat culture (24:0 h; 51.8%) than those cultured for 24 h with repeat culture (24:6 h; 26.1%) and nonfrozen oocytes (25.9%). However, the proportion of male pronucleus (MPN) in the group of 24:0 h (32.4%) was significantly (P<0.05) lower than that of nonfrozen oocytes (64.3%); the formation of the female pronucleus and MPN were also significantly (P<0.01) lower (17.2%) than that of nonfrozen oocytes (56.1%). Polyspermic oocytes cultured for 18 h with repeat culture for 6 h (18:6 h) were significantly (P<0.05) higher (47.5%) than for nonfrozen oocytes (25.6%). Development to 8-cell stage in the group of 18:6 h was significantly (P<0.05) lower (1.6%) than that of nonfrozen oocytes (18.5%). The cleavage rates in the groups of 24:0 h (16.3%) and 24:6 h (23.4%) were also significantly (P<0.05) lower than for nonfrozen oocytes (63.3%). Development to blastocysts was low (3.9%), but hatched blastocysts were observed in frozen-thawed oocytes cultured for 18:0 h. These results indicate the post-thaw 6-h repeat culture did not greatly improve the fertilizability and embryonic development of oocytes cultured for 18 h or 24 h before freezing. Frozen-thawed oocytes after 24 h in vitro maturation without repeat culture especially had impaired capacities for fertilizability and development.

Animals↗
PubMed2000

Contribution of automated hematology analysis to the detection of apoptosis in peripheral blood lymphocytes.

Automated hematology analyzers (analyzers) can provide complete blood counts and white blood cell (WBC) differentials in clinical laboratories and alert users to the presence of quantitative and qualitative cell abnormalities through cautionary flags. In this study, we applied analyzers to the screening of apoptotic cells in peripheral blood and examined the triggering capacity of cautionary flags to detect apoptotic cell populations. EDTA-anticoagulated fresh peripheral blood from patients with acute infectious mononucleosis containing atypical lymphocytes comprising 12.3 +/- 4. 0% of WBC was applied to a Beckman-Coulter MAXM A/L Retic (MAXM) analyzer. The lymphocyte cluster spread upward in VOLUME/DF1 scattergrams and the threshold lines between lymphocyte and monocyte clusters shifted upward. Flags for the number and percentage of lymphocytes, variant lymphocytes, and blast cells were generally present for samples containing atypical lymphocytes. After the blood from acute infectious mononucleosis patients was incubated for 4 h at 37 degrees C, peripheral blood smears revealed the presence of morphologically apoptotic cells comprising 9.0 +/- 4.2% of WBC and a comparable reduction of lymphocytes. On the MAXM analyzer, the apoptotic lymphocyte cluster appeared under the lymphocyte cluster in VOLUME/DF1 scattergrams. However, no specific flag was present to alert users to the presence of the apoptotic lymphocyte cluster. We conclude that visual inspection of scattergrams generated by the MAXM analyzer can be useful for the detection of apoptotic lymphocytes in peripheral blood. Cytometry (Comm. Clin. Cytometry) 42:209-214, 2000. Published 2000 Wiley-Liss, Inc.

Apoptosis↗
PubMed2000

Human cytotoxic T-lymphocyte responses specific for peptides of the wild-type Wilms' tumor gene (WT1 ) product.

The product of the Wilms' tumor gene WT1 is a transcription factor overexpressed not only in leukemic blast cells of almost all patients with acute myeloid leukemia, acute lymphoid leukemia, and chronic myeloid leukemia, but also in various types of solid tumor cells. Thus, it is suggested that the WT1 gene plays an important role in both leukemogenesis and tumorigenesis. Here we tested the potential of WT1 to serve as a target for immunotherapy against leukemia and solid tumors. Four 9-mer WT1 peptides that contain HLA-A2.1-binding anchor motifs were synthesized. Two of them, Db126 and WH187, were determined to bind to HLA-A2.1 molecules in a binding assay using transporter associated with antigen processing-deficient T2 cells. Peripheral blood mononuclear cells from an HLA-A2.1-positive healthy donor were repeatedly sensitized in vitro with T2 cells pulsed with each of these two WT1 peptides, and CD8(+) cytotoxic T lymphocytes (CTLs) that specifically lyse WT1 peptide-pulsed T2 cells in an HLA-A2.1-restricted fashion were induced. The CTLs also exerted specific lysis against WT1-expressing, HLA-A2.1-positive leukemia cells, but not against WT1-expressing, HLA-A2.1-negative leukemia cells, or WT1-nonexpressing, HLA-A2. 1-positive B-lymphoblastoid cells. These data provide the first evidence of human CTL responses specific for the WT1 peptides, and provide a rationale for developing WT1 peptide-based adoptive T-cell therapy and vaccination against leukemia and solid tumors.

CD3 Complex↗
PubMed2000

Diagnosis and treatment of 6-pyruvoyl-tetrahydropterin synthase deficiency.

We detected a case of 6-pyruvoyl tetrahydropterin synthase (PTPS) deficiency during a neonatal mass screening and considered the differentiation and treatment of the peripheral form of PTPS deficiency. Although single treatment of BH4 had been started, because of the lowered biopterin (B) value, elevated neopterin (N) value, and N/B ratio in the cerebrospinal fluid (CSF), the peripheral form was judged negative and combined treatment with L-dopa and 5-hydroxy tryptophan (5-HTP) was started. Follow-up study will be necessary to confirm the diagnosis of PTPS deficiency.

Biopterins↗
PubMed2000

Synthesis and antitumor activity of duocarmycin derivatives: modification at C-8 position of A-ring pyrrole compounds bearing the simplified DNA-binding groups.

A series of the 8-O-substituted A-ring pyrrole derivatives of duocarmycin bearing the simplified DNA-binding moieties such as cinnamoyl or heteroarylacryloyl groups were synthesized, and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. In addition, the stability of the 8-O-substituted analogues in aqueous solution and the conversion to their active form (cyclopropane compound) from the 8-O-substituted analogues in mice or human serum were examined. The 8-O-substituted A-ring pyrrole derivatives bearing the simplified DNA-binding moieties showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the 8-O-substituted A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment-B (Seg-B), which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates and 4'-methoxy-beta-heteroarylacrylates. Moreover, among 8-O-substituted analogues, several compounds can be chemically or enzymatically converted to their active form in human serum. This result indicated that new 8-O-substituted derivatives were different prodrugs from KW-2189 and 8-O-substituted analogues being the same type of prodrug as KW-2189.

Animals↗
PubMed2000

New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals.

Only a few RFamide peptides have been identified in mammals, although they have been abundantly found in invertebrates. Here we report the identification of a human gene that encodes at least three RFamide-related peptides, hRFRP-1-3. Cells transfected with a seven-transmembrane-domain receptor, OT7T022, specifically respond to synthetic hRFRP-1 and hRFRP-3 but not to hRFRP-2. RFRP and OT7T022 mRNAs are expressed in particular regions of the rat hypothalamus, and intracerebroventricular administration of hRFRP-1 increases prolactin secretion in rats. Our results indicate that a variety of RFamide-related peptides may exist and function in mammals.

Amino Acid Sequence↗
PubMed2000

Engineering of an FGF-proteoglycan fusion protein with heparin-independent, mitogenic activity.

In the absence of heparan sulfate (HS) on the surface of target cells, or free heparin (HP) in the vicinity of their receptors, fibroblast growth factor (FGF) family members cannot exert their biological activity and are easily damaged by proteolysis. This limits the utility of FGFs in a variety of applications including treatment of surgical, burn, and periodontal tissue wounds, gastric ulcers, segmental bony defects, ligament and spinal cord injury. Here we describe an FGF analog engineered to overcome this limitation by fusing FGF-1 with HS proteoglycan (PG) core protein. The fusion protein (PG-FGF-1), which was expressed in Chinese hamster ovary cells and collected from the conditioned medium, possessed both HS and chondroitin sulfate sugar chains. After fractionation, intact PG-FGF-1 proteins with little affinity to immobilized HP and high-level HS modification, but not their heparitinase or heparinase digests, exerted mitogenic activity independent of exogenous HP toward HS-free Ba/F3 transfectants expressing FGF receptor. Although PG-FGF-1 was resistant to tryptic digestion, its physiological degradation with a combination of heparitinase and trypsin augmented its mitogenic activity toward human endothelial cells. The same treatment abolished the activity of simple FGF-1 protein. By constructing a biologically active proteoglycan-FGF-1 fusion protein, we have demonstrated an approach that may prove effective for engineering not only FGF family members, but other HP-binding molecules as well.

Amino Acid Sequence↗
PubMed2000

ATM protein and p53-serine 15 phosphorylation in ataxia-telangiectasia (AT) patients and at heterozygotes.

ATM (ataxia-telangiectasia mutated) gene plays a central role in the DNA-damage response pathway. We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. On Western blots, the full-length ATM protein was detected in eight of 18 AT cases, albeit at 1-32% of the normal levels, whereas a truncated ATM protein was detected in a single case, despite the prevalence among cases of truncation mutations. Of two ataxia without telangiectasia [A-(T)] cases, one expressed 20% and the other approximately 70% of the normal ATM levels. Noteworthy, among ten asymptomatic heterozygous carriers for AT, normal amounts of ATM protein were found in one and reduced by 40-50% in the remaining cases. The radiation-induced phosphorylation of p53 protein at serine 15, largely mediated by ATM kinase, was defective in AT, A(-T) and in 2/4 heterozygous carriers, while the G1 cell cycle checkpoint was disrupted in all AT and A(-T) cases, and in 3/10 AT heterozygotes. Altogether, our study shows that AT and A(-T) cases bearing truncation mutations of the ATM gene can produce modest amounts of full-length (and only rarely truncated) ATM protein. However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway.

Ataxia Telangiectasia↗
PubMed2000

In vitro maturation and ultrastructural observation of cryopreserved minke whale (Balaenoptera acutorostrata) follicular oocytes.

Minke whale (Balaenoptera acutorostrata) follicular oocytes were cryopreserved by a slow-step freezing procedure using ethylene glycol. The morphologically viable proportion of postthawed minke whale follicular oocytes was 39.7%. The maturity of the animals (immature and mature whales) or the presence or absence of cumulus cells (CC) did not affect the proportion of morphologically viable oocytes. Postthawed oocytes were examined for nuclear status after in vitro maturation. The presence of CC (29.1%) significantly enhanced (P < 0.05) the proportion of oocytes at metaphase I/anaphase I/telophase I stages compared to results with the absence of CC (13.5%). A total of 4 of 194 postthawed oocytes matured to the second metaphase stage after culture for 5.5 days with or without CC. The cryopreserved immature oocytes obtained from immature and mature whales were processed to examine the ultrastructure by transmission electron microscopy. Varying ultrastructural damage to the cytoplasm was observed as a result of the cryopreservation procedures. These results show that 20-30% of cryopreserved minke whale follicular oocytes can resume meiosis in vitro, but damage induced by the freezing and thawing procedures was observed.

Animals↗
PubMed2000

Molecular cloning of mouse alpha-1,6-fucosyltransferase and expression of its mRNA in the developing cerebrum.

Complementary DNA encoding mouse alpha-1,6-fucosyltransferase (FUT) was cloned. The deduced primary structure consisted of 575 amino acids and had 96.0% and 93.0% identity with alpha-1,6-FUT of human and porcine origin, respectively. Quantitative analysis of alpha-1,6-FUT mRNA expression during selected developmental stages of the cerebrum showed that the expression increased during later embryonic stages and was highest in the early postnatal stages (P1 to P7), after which it declined somewhat but still remained relatively high in the mature adult. The expression profile suggests important roles of FUT in the developing central nervous system.

Amino Acid Sequence↗
PubMed2000

[Dysregulation of the genes controlling apoptosis in cancer development].

Apoptosis is a cellular self-destruction mechanism involved in a variety of biological events. Cancer is a disorder of autonomous cell proliferation and accumulation, which is associated with the failure to undergo apoptosis in response to appropriate stimuli. Inhibition of apoptosis may be a prerequisite or acquired biological feature of various cancer cells. Resistance to apoptosis is achieved either by an increase in apoptosis resistance or decrease in apoptosis sensitivity. Some of the hereditary cancer syndrome patients have mutations in the genes to induce apoptosis, eventually leading to inhibition of apoptosis and cancer development.

Apoptosis↗
PubMed2000

Early lesions of cerebral atherosclerosis from induced hypertension in Watanabe heritable hyperlipidemic rabbits.

Watanabe heritable hyperlipidemic (WHHL) rabbits are well known to develop severe atherosclerotic lesions in extracranial arteries but not in cerebral arteries. In the present work we produced and investigated atherosclerotic lesions in cerebral arteries of WHHL rabbits by inducing hypertension. Hypertension was induced by right nephrectomy and surgically induced stenosis of the left renal artery. Six months after surgery the rabbits were killed for morphologic, immunohistochemical and transmission electron microscopic studies of extracranial and cerebral atherosclerosis. A significant rise in systolic blood pressure was evident 3 months after surgery in the hypertensive group (p < .001). Atherosclerotic lesions had developed areas near the vertebral-basilar arterial confluence and the circle of Willis in the hypertensive Watanabe rabbits by 6 months after surgery (p < .001). Atherosclerotic lesions in cerebral arteries remained less severe than in the aorta and coronary arteries, and showed qualitative morphologic differences. This is the first report of production by hypertension of experimental cerebral atherosclerosis in the WHHL rabbits, indicating that hypertension as well as hyperlipidemia was required for development of lesions in cerebral arteries. This model should be useful for studying development of cerebral atherosclerosis and may contribute to improved prevention and treatment of the human disease.

Animals↗