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Biomedical subjects

K Nagata

Publications and source records attributed to K Nagata.

At least 181 records · Page 10Linked to original sources
PubMed2000

Pharmacogenetics of sulfotransferase.

Cytosolic sulfotransferase catalyzes sulfoconjugation of relatively small lipophilic endobiotics and xenobiotics. At least 44 cytosolic sulfotransferases have been identified from mammals, and based on their amino acid sequences, these forms are shown to constitute five different families. In humans, 10 sulfotransferase genes have been identified and shown to localize on at least five different chromosomes. The enzymatic properties characterized in the recombinant forms indicate the association of their substrate specificity with metabolisms of such nonpeptide hormones as estrogen, corticoid, and thyroxine, although most forms are also active on the sulfation of various xenobiotics. Genetic polymorphisms are observed on such human sulfotransferases as ST1A2, ST1A3, and ST2A3.

Animals↗
PubMed2000

Altered beta-adrenergic signal transduction in nonfailing hypertrophied myocytes from Dahl salt-sensitive rats.

Desensitization of the beta-adrenergic receptor (beta-AR) response is well documented in hypertrophied hearts. We investigated whether beta-AR desensitization is also present at the cellular level in hypertrophied myocardium, as well as the physiological role of inhibitory G (G(i)) proteins and the L-type Ca(2+) channel in mediating beta-AR desensitization. Left ventricular (LV) myocytes were isolated from hypertrophied hearts of hypertensive Dahl salt-sensitive (DS) rats and nonhypertrophied hearts of normotensive salt-resistant (DR) rats. Cells were paced at a rate of 300 beats/min at 37 degrees C, and myocyte contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) were simultaneously measured. In response to increasing concentrations of isoproterenol, DR myocytes displayed a dose-dependent augmentation of cell shortening and the [Ca(2+)](i) transient amplitude, whereas hypertrophied DS myocytes had a blunted response of both cell shortening and the [Ca(2+)](i) transient amplitude. Interestingly, inhibition of G(i) proteins did not restore beta-AR desensitization in DS myocytes. The responses to increases in extracellular Ca(2+) and an L-type Ca(2+) channel agonist were also similar in both DS and DR myocytes. Isoproterenol-stimulated adenylyl cyclase activity, however, was blunted in hypertrophied myocytes. We concluded that compensated ventricular hypertrophy results in a blunted contractile response to beta-AR stimulation, which is present at the cellular level and independent of alterations in inhibitory G proteins and the L-type Ca(2+) channel.

Adenylate Cyclase Toxin↗
PubMed2000

Clinicopathological study of intracranial fusiform and dolichoectatic aneurysms : insight on the mechanism of growth.

BACKGROUND AND PURPOSE: Intracranial fusiform aneurysms can be divided into 2 clinically different subtypes: acute dissecting aneurysms and chronic fusiform or dolichoectatic aneurysms. Of these 2, the natural history and growth mechanism of chronic fusiform aneurysms remains unknown. METHODS: A consecutive series of 16 patients with chronic fusiform aneurysms was studied retrospectively to clarify patient clinical and neuroradiological features. Aneurysm tissues were obtained from 8 cases and were examined to identify histological features that could correspond to the radiological findings. RESULTS: Four histological features were found: (1) fragmentation of internal elastic lamina (IEL), (2) neoangiogenesis within the thickened intima, (3) intramural hemorrhage (IMH) and thrombus formation, and (4) repetitive intramural hemorrhages from the newly formed vessels within thrombus. IEL fragmentation was found in all cases, which suggests that this change may be one of the earliest processes of aneurysm formation. MRI or CT detected IMH, and marked contrast enhancement of the inside of the aneurysm wall (CEI) on MRI corresponded well with intimal thickening. Eight of 9 symptomatic cases but none of 7 asymptomatic cases presented with both radiological features. CONCLUSIONS: Data suggest that chronic fusiform aneurysms are progressive lesions that start with IEL fragmentation. Formation of IMH seems to be a critical event necessary for lesions to become symptomatic and progress, and this can be monitored on MRI. Knowledge of this possible mechanism of progression and corresponding MRI characteristics could help determine timing of surgical intervention.

Adult↗
PubMed2000

Prediction of embolism in atrial fibrillation: classification of left atrial thrombi by transesophageal echocardiography.

The current study was undertaken to clarify the relationship between cerebral/arterial embolism and the morphology of left atrial thrombi. Forty-one patients with atrial fibrillation and left atrial thrombi were followed for 1 year, using transesophageal echocardiography (TEE) to study how the shape, site, movability, number and maximum dimension of left atrial thrombi are related to embolism. Left atrial thrombi were classified by their shape and movability into movable ball (MB) type (n=13), fixed ball (FB) type (n=17) and mountain (MN) type (n=11). The thrombi were also classified by location into the interior section (n=3), middle section (n=8), and the entrance section (n=19) of the left atrial appendage, and the section outside of the left atrial appendage (n=11). The rate of embolism in the MB-type group was significantly higher than that in the other groups (ie, MB 76.9% vs FB 17.6% (p<0.01) vs MN 9.1%; p<0.01), which indicates that the MB-type thrombus is an important risk factor for cerebral/arterial embolism.

Adult↗
PubMed2000

Intestinal cytochrome P450 and response to rifampicin in rabbits.

Properties of cytochrome P450 (P450) in rabbit intestines have been investigated to assess the possibility of an experimental model for human intestinal oxidation of drugs. Significant amounts of P450 and cytochrome b5 and activities of NADPH-cytochrome P450 reductase were detected in microsomes from rabbit duodenal, jejunal, ileac and colon mucosa. All the small intestinal fractions mediated phenytoin, dextromethorphan and testosterone oxidations. Several P450 forms belonging to the CYP1A, CYP2C, CYP2D and CYP3A, but not CYP2B and CYP2E, subfamilies were detected in these tissues by Western blotting. A good correlation was observed between immunodetectable levels of CYP3A and activities of testosterone 6beta-hydroxylation. Small intestine, but not colon, CYP3A levels were increased by the pretreatment of rabbits with rifampicin (50 mg/kg for 4 days, p.o.). The extent of the increase was similar between duodena and livers. These properties of rabbit intestinal P450s were comparable to those of human intestine. These phenomena suggest the possibility that the rabbit is a beneficial in vivo model for the assessment of drug interaction occurring at the first pass of drugs ingested.

Animals↗
PubMed2000

The effect of the patellar tendon-bearing cast on loading.

We assessed the unloading effect of the patellar tendon-bearing (PTB) cast in five healthy volunteers using a new system for analysis of dynamic plantar pressure. We devised a method to improve the unloading effect of the PTB cast, and tested this using the same system. Our findings showed that the conventional PTB cast only achieved unloading of 30% of the body-weight and that the part of the cast on the leg had a more important role in the unloading than that which was in contact with the patellar tendon. When the depth of the free space under the foot inside the PTB cast was 1, 2 and 3 cm, the unloading effect was 60%, 80% and 98%, respectively. The unloading effect of the conventional PTB cast was disappointing at only 30% of body-weight. It was improved by producing a space between the sole of the foot and the cast, and was adjustable by altering the depth of this space.

Adult↗
PubMed2000

The expression and cellular localization of the sperm flagellar protein MC31/CE9 in the rat testis: possible posttranscriptional regulation during rat spermiogenesis.

We isolated the MC31 cDNA clone coding the antigen specifically recognized by the monoclonal antibody mMC31, and found that MC31 was identical to rat CE9. Therefore, this molecule is called MC31/CE9. MC31/CE9, a member of the immunoglobulin superfamily molecules, was localized on the rat sperm flagellar plasma membrane. We analyzed the expression and cellular localization of MC31/CE9 mRNA and protein in the adult rat testis by use of Northern hybridization, in situ hybridization, and immunohistochemical analyses. In the course of spermatogenesis, MC31/CE9 mRNA first appeared in type B spermatogonia. The mRNA signal intensity increased progressively to pachytene spermatocytes and remained constantly at a considerable level throughout the subsequent phases of spermatocytes and round spermatids, and then decreased gradually from step-11 spermatids to disappear in step-15 spermatids. On the other hand, MC31/CE9 protein expression showed a bimodal pattern. Immunohistochemical analysis for the MC31/CE9 protein revealed its most intense immunoreactivity on the flagella of step-8 to step-19 elongated spermatids. The cytoplasmic immunoreactivity of the MC31/CE9 protein also appeared in preleptotene to early pachytene spermatocytes and elongated spermatids, with particularly intense immunoreactivity in the Golgi complexes of zygotene and early pachytene spermatocytes (stage XIII to III) as well as step-8 to step-13 spermatids. Between these two phases, the MC31/CE9 protein proved undetectable in the cytoplasm of any spermatogenic cells. Sertoli cells and Leydig cells were devoid of MC31/CE9 mRNA and its protein. Therefore, the production of MC31/CE9 is thought to be posttranscriptionally regulated during spermiogenesis.

Animals↗
PubMed2000

Neuropsychological changes after surgery for anterior communicating artery aneurysm.

Neuropsychological disturbances following surgery for anterior communicating artery aneurysms were analyzed in 26 patients (11 males, 15 females) using the Hasegawa dementia scale-revised (HDS-R) over a 3-year period. The patients were aged from 34 to 76 years (mean 54.1 years). Lesions in the frontal lobe were evaluated using computed tomography (CT). Twenty-three patients had symptoms over the course. Four patients had basal forebrain lesion, five had ventral frontal lesion, and 12 had no lesion. Patients with basal forebrain lesion and no lesion tended to show disorientation. The mean HDS-R score was 10.2 points in the patients with ventral frontal lesion, and 13.5 points in the patients with no lesion. These scores are within the range for dementia. The mean HDS-R score in patients with basal forebrain and striate lesions was over 25 points and beyond the range for dementia. Significant differences were observed in the HDS-R score between patients with ventral frontal lesion and basal forebrain lesion, and between patients with no lesion and basal forebrain lesion (p < 0.05). Recovery from neuropsychological disturbances was poorer in patients with ventral frontal lesion and no lesion compared to those with basal forebrain and striate lesions, and their symptoms tended to persist.

Adult↗
PubMed2000

Effect of age on cerebral venous circulation disturbances in the rat.

OBJECT: Mild cerebral venous circulation disturbances (CVCDs) in aged patients are frequently known to cause unexpectedly severe postoperative complications in neurosurgical practice. The object of the present study was to determine whether there are age-related differences involved in vulnerability to CVCDs. METHODS: Thirty-eight male Wistar rats were used. A single cortical vein with a 100-microm diameter was occluded photochemically by using rose bengal dye and fiberoptic illumination in young (Group Y, 19 animals aged 10-14 weeks) and aged (Group A, seven animals aged 80-100 weeks) rats. Five young and seven aged animals served as sham-operated controls. Regional cerebral blood flow (rCBF) was determined from local CBF, which was measured at 25 (5 x 5) identical locations, with the occluded vein located central to the scanning field, by using a laser Doppler scanning technique every 15 minutes for 90 minutes after venous occlusion. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after occlusion. Histological specimens were examined 24 hours after occlusion. In Group Y, rCBF did not change significantly after venous occlusion. However, in Group A, rCBF decreased rapidly beginning 15 minutes after occlusion. Significant intergroup differences were observed 30, 60, and 90 minutes after occlusion. Venous flow arrest, which resulted in venous infarct, was observed on angiography 90 minutes after occlusion in two (10.5%) of 19 young and six (85.7%) of seven aged rats. The venous thrombus in Group A rats was significantly larger than that in Group Y rats 90 minutes after occlusion. Venous infarction was seen in all aged rats (100%) and in six young rats (31.6%); the infarct size, expressed as a percentage of the size of the ipsilateral hemisphere, was significantly larger in aged rats than in young rats. CONCLUSIONS: This study demonstrated an age-related increase in the rate and size of venous infarct following vein occlusion, suggesting that the greater vulnerability to CVCDs in the aged brain might be attributed to early and extensive hypoperfusion of circumscribed brain areas drained by the occluded vein. The larger thrombus formation in aged animals indicates that a shift in the thrombogenetic/thrombolytic equilibrium is responsible for the observed effect.

Aging↗
PubMed2000

Regional cerebral blood flow after status epilepticus.

Two patients with status epilepticus due to specific conditions were examined using MRI and stable Xe/CT CBF. [Case 1] A 30-year-old woman developed a grand mal seizure during delivery. She was comatose, and MRI revealed abnormal high intensity areas bilateral basal ganglia, compatible with eclampsia. Regional CBF was decreased in bilateral occipital lobes and right basal ganglia. Six days after onset. Regional gray matter flow was increased, especially in the thalami and basal ganglia. [Case 2] The patient is a 31-year-old male diagnosed with temporal lobe epilepsy since 10 years. At the onset, he had a prolonged right hemiconvulsion followed by generalized tonic-clonic convulsion. MRI 13 days after onset showed left hemispheric edematous swelling of gray matter. Stable Xe/CT 3 weeks after onset demonstrated increased cortical CBF corresponding to edematous area. The results suggested that regional CBF decreased immediately after status epilepticus and then increased for 1-3 weeks in the interictal period. We speculate that the energy debt incurred during prolonged seizure causes relative ischemic condition in the neurons, with the increase in CBF resulting from accelerated energy production for a long period.

Adult↗
PubMed2000

[Successful treatment of refractory thrombotic thrombocytopenic purpura with cyclosporine A and splenectomy].

A 19-year-old girl was admitted to our hospital because of general fatigue, headache and purpura. A number of her laboratory findings suggested hemolytic anemia and thrombocytopenia. Direct/indirect Coombs tests gave negative results. Although the patient had no neurological or renal abnormalities, peripheral blood smears showed marked red cell fragmentation, and therefore she was diagnosed as having thrombotic thrombocytopenic purpura (TTP). Fresh frozen plasma (FFP) was transfused daily. The thrombocytopenia and hemolysis immediately improved, but worsened again after reduction of the FFP transfusion. Plasma exchange was instituted every other day, but the patient's condition worsened. Palsy and consciousness disturbance developed, and finally she lapsed into a coma. Daily plasma exchange and methylprednisolone pulse therapy were performed, together with weekly vincristine therapy, and this led to a gradual improvement in the patient's condition. However, several attempts at weaning from plasma exchange resulted in exacerbation of the TTP activity. Therefore oral cyclosporine A was started and splenectomy was performed. After these interventions, despite transient relapse, the patient was successfully weaned off the FFP transfusion, and she is now in remission. Because in this case splenectomy and cyclosporine A resulted in sustained remission of TTP that was refractory to intensive plasma therapy, an autoimmune mechanism may have been involved in the pathogenesis.

Adult↗
PubMed2000

[Vascular and metabolic reserve in a case of hypoplasia of bilateral internal carotid arteries].

We report a 64-year-old right-handed man who presented with a hypoplasia of bilateral internal carotid arteries (ICAs). The patient complained of a vertigo and was diagnosed as having a benign paroxysmal positional vertigo. Upon neurological examination, he was completely free from neurological deficits. MR angiogram revealed an occlusion of both ICAs. On conventional angiogram, the right ICA was occluded about 3 cm distal from its origin, and the left ICA was occluded at the precavernous portion. There was an abundant collateral blood flow to the frontal, temporal and parietal lobes through the posterior communicating arteries. Both carotid canals were hypoplastic on 3D-CT. The patient was then diagnosed as having a hypoplasia of both ICAs. Using a positron emission tomography (PET), cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO2), oxygen extraction fraction (OEF), and vascular transit time (VTT) were measured during resting state, and the vascular reactivities to carbon dioxide inhalation (VRCO2), and to the intravenous administration of Acetazolamide (VRACZ) were also evaluated. There was no global or focal reduction in CBF and VTT was within normal limit, whereas a global reduction of CMRO2 caused mild decrease in OEF. Moreover, VRACZ was significantly decreased and an intracerebral steal phenomenon was observed in the parietal cortical areas, whereas VRCO2 was preserved. The discrepancy between VRACZ and VRCO2 observed could be related to the differences in the mechanisms underlying the vasodilating effects of carbon dioxide and ACZ.

Arterial Occlusive Diseases↗
PubMed1999

Prothoracicotropic activity of SBRPs, the insulin-like peptides of the saturniid silkworm Samia cynthia ricini.

Synthesis and secretion of the insect molting hormone ecdysteroid in the prothoracic glands (PGs) are stimulated by the prothoracicotropic hormone (PTTH) secreted by the brain. Bombyxins, insulin-like peptides of the silkworm Bombyx mori, show prothoracicotropic activity when administered to the saturniid silkworm Samia cynthia ricini, but they are inactive to B. mori itself. Recently, the genes for the bombyxin homologs of S. cynthia ricini (referred to as Samia bombyxin-related peptides, SBRPs) were cloned. To examine the prothoracicotropic activity of SBRPs on S. cynthia ricini, we synthesized two representative molecules, SBRP-A1 and -B1. They promoted pupa-to-adult development with ED(50) of 50 and 10 ng/pupa (EC(50) of 5 and 1 nM), respectively.

Amino Acid Sequence↗
PubMed1999

Histone- and chromatin-binding activity of template activating factor-I.

Template activating factor-I (TAF-I) is a histone-binding chromatin remodeling factor. We recently found that TAF-I is capable of mediating decondensation of Xenopus sperm chromatin by releasing sperm-specific basic proteins. Here we present evidence that TAF-I preferentially binds to histone H3 among four core histones. Immunofluorescent staining revealed that TAF-I binds to the decondensed sperm chromatin, of which protein components predominantly consist of histones H3 and H4.

Animals↗
PubMed1999

(-)-Epigallocatechin gallate inhibits mos activation-mediated xenopus oocyte maturation induced by progesterone.

(-)-Epigallocatechin gallate (EGCG), one of the constituents of green tea known to have a tumor preventing effect, inhibited maturation of Xenopus laevis oocytes induced by progesterone when this polyphenol was microinjected into oocytes at a final concentration of about 1 mM. Western blot and activity measurement analyses showed that Mos translation and the subsequent activations of mitogen-activated protein kinase and p90(rsk), probably by protein phosphorylation, seemed to have been inhibited by the microinjection of EGCG. These results suggest that EGCG may have the ability to control Xenopus oocyte maturation at least during the stage of Mos activation.

Animals↗
PubMed1999

Separate cis-acting DNA elements control cell type- and tissue-specific expression of collagen binding molecular chaperone HSP47.

HSP47 is a collagen-binding heat shock protein and is assumed to act as a molecular chaperone in the biosynthesis and secretion of procollagen. As the synthesis of HSP47 is closely correlated with that of collagen in various cell lines and tissues, we performed a promoter/reporter assay using HSP47-producing and nonproducing cells. 280 base pairs (bp(s)) of upstream promoter were shown to be necessary for the basal expression but not to be enough for the cell type-specific expression. When the first and the second introns were introduced downstream of this 280-bp region, marked up-regulation of the reporter activity was observed in HSP47-producing cells but not in nonproducing cells. This was confirmed in transgenic mice by staining the lacZ gene product under the control of the 280-bp upstream promoter and the introns. Staining was observed in skin, chondrocytes, precursor of bone, and other HSP47/collagen-producing tissues. A putative Sp1-binding site at -210 bp in the promoter, to which Sp3 and an unidentified protein bind, was shown to be responsible for this up-regulation when combined with the introns. However no difference in the binding to this probe was observed between HSP47-producing and nonproducing cells. The responsible region for cell type-specific up-regulation was found to be located in a 500-bp segment in the first intron. On electrophoresis mobility shift assay using this 500-bp probe, specific DNA-protein complexes were only observed in HSP47-producing cell extracts. These results suggest that two separate elements are necessary for the cell type-specific expression of the hsp47 gene; one is a putative Sp1-binding site at -210 bp necessary for basal expression, and the other is a 500-bp region within the first intron, required for cell type-specific expression.

3T3 Cells↗