Biomedical subjects

H Iida

Publications and source records attributed to H Iida.

At least 271 records · Page 15Linked to original sources

PubMed1995

[Evaluation of partial volume effect in quantitative measurement of regional cerebral blood flow in single photon emission computed tomography--effects of limited spatial resolution and first-pass extraction fraction].

Two numerical brain phantoms were generated in order to investigate errors which might be included in the quantitative measurement of regional CBF with use of single photon emission computed tomography (SPECT). The first phantom simulated the normal brain, and effects of the limited spatial resolution of the SPECT scanner were evaluated for 4 tracer kinetic models of the conventional microsphere model, the intra-carotid bolus injection technique of 133Xe, 133Xe Kanno-Lassen method, and the IMP-autoradiography (IMP-ARG) method. The second phantom simulated the diseased brain with middle-carotid artery (MCA) occlusion, and effects of the limited first-pass extraction fraction were investigated for the microsphere model with various permeability-surface area products. The limited spatial resolution caused systematic underestimation of the radioactivity concentration in the gray matter regions, and systematic overestimation in the low CBF regions. These errors in the original radioactivity distribution were found to cause further systematic errors in the calculated regional CBF images. It was also found that these errors were highly dependent on the tracer kinetic model employed, e.g., regional CBF values were overestimated in the clearance and the Kanno-Lassen methods compared with the conventional microsphere method, whereas values were underestimated in the IMP-ARG method. It was also shown in this study that the limited first-pass extraction fraction caused significant underestimation in the calculated rCBF values. In addition, regional contrast can be reduced when using a tracer with small PS product.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain↗

PubMed1995

[Evaluation of partial volume effect in quantitative measurement of regional cerebral blood flow using positron emission tomography].

Effects of limited spatial resolution of the positron emission tomography (PET) scanner on the quantitative measurement of regional cerebral blood flow (rCBF) was investigated for various tracer kinetic models with use of 15O labeled water and PET. Using a numerical brain phantom consisting of a gray matter, white matter and cerebrospinal fluid components, dynamical tracer distribution images were calculated for the H215O bolus injection and for the C15O2 gas inhalation protocols. The tracer distribution images were convoluted with a 2 dimensional gaussian function with full-width at half maximum (FWHM) of 4, 7, 12 mm to simulate a limited spatial resolution of the PET scanner, and rCBF images were calculated according to some kinetic models. Smoothing the tracer distribution images caused a heterogeneous structure (tissue mixture) in a given volume element. rCBF values calculated by models with use of 15O-water and PET were found to provide rCBF values that were systematically underestimated compared with those obtained by the microsphere model for a mixed tissue region. Moreover, the magnitude of the underestimation was shown to be highly dependent on the tracer kinetic models employed, those errors for mixed tissue of gray and white matter were 20% on steady state, 9% on autoradiography and on weighted integration method, and 2% on non-linear least squares fitting, compared with microsphere model. More errors observed by steady state method and autoradiography method happened for tissue mixture consisting gray matter, white matter and cerebrospinal fluid components. It is important to take into account for difference of the partial volume effect for each models in calculated rCBF.

Brain↗

PubMed1995

[Quantitation of regional cerebral blood flow using 123I-IMP from a single SPECT scan and a single blood sampling--analysis on statistical error source and optimal scan time].

Recently, a method has been proposed to measure quantitative regional cerebral blood flow (rCBF) in man using N-isopropyl-p-[123I]-iodoamphetamine (IMP) and single photon emission tomography (SPECT). In this method (IMP-ARG method), a functional map of rCBF was calculated from a single SPECT scan data set, in which effects of the clearance of IMP from the brain was taken into account by employing the 2 compartment model. To avoid the procedures of frequent and/or continuous sampling of the arterial blood that was required in determination of the input function, use of a standard input function and calibrating it by one blood sampling were validated. The present study was intended to investigate the sensitivity to various sources of errors in the IMP-ARG method such as (1) effects of individual difference of the arterial input function, (2) effects of ambiguity of the regional distribution volume (Vd) of IMP, and (3) effects of inaccuracy of the SPECT measurement. It was shown in the present simulation study that errors in the calculated rCBF values were dependent on the SPECT mid-scan time (MST), and that the minimum error corresponded to the MST of approximately 30 min after the IMP infusion. With this optimal MST, errors in rCBF due to the individual difference of the input function was approximately 10%, and the errors due to the ambiguity of the Vd were approximately 8%. The total accuracy of the calculated rCBF in the IMP-ARG method was, therefore, estimated as approximately 13%. Although a relatively large error was expected at a high rCBF area, this study strongly suggested the IMP-ARG method being useful and accurate for providing the quantitative rCBF map for a clinical use.

Amphetamines↗

PubMed1995

Aging effect on neutral amino acid transport at the blood-brain barrier measured with L-[2-18F]-fluorophenylalanine and PET.

UNLABELLED: Neutral amino acids (NAAs) are transported from the blood to the brain using the same carrier system in a competitive fashion. The purpose of this study is to establish a method for evaluating neutral amino acid transport at the blood-brain barrier (BBB) in humans and to examine the aging effect of amino acid transport. METHODS: A dynamic PET study with L-(2-18F)-fluorophenylalanine (18F-Phe) was performed in 14 normal volunteers (age 21-71 yr; mean +/- s.d., age range 48.0 +/- 17.1 yr). By using a two-compartment model analysis and a weighted integration technique, the influx rate constant K1, the efflux rate constant k2 and distribution volume Vd of 18F-Phe were estimated in various brain structures. RESULTS: The value of K1 was inversely correlated with plasma NAA concentration (r = -0.69, p < 0.01). The cerebellum showed the highest value of K1, while the white matter showed the lowest. There was no significant change in K1 during aging. The value of k2 was significantly increased with age. CONCLUSION: No decline of K1 during aging indicated that NAA transport from the blood to the brain is a limiting process of age in amino acid incorporation. Fluorine-18-Phe PET imaging is a feasible method to study NAA transport at the BBB in vivo in humans and can be applied to pathological conditions of the brain.

Adult↗

PubMed1995

Myocardial blood flow: comparison of oxygen-15-water bolus injection, slow infusion and oxygen-15-carbon dioxide slow inhalation.

UNLABELLED: This study investigates the most appropriate protocol for measuring regional myocardial blood flow (MBF) using 15O-water in clinical applications. METHODS: Regional MBF, perfusable tissue fraction (PTF) and arterial blood volume (Va) were measured using 15O-water and dynamic PET on five healthy volunteers based on previously published models. Calculated values were compared for the following three tracer administration protocols: 15O-water bolus injection, 15O-water slow (2 min) infusion and 15O-carbon dioxide slow (2 min) inhalation. For the two slow administration protocols, the three parameters MBF, PTF and Va were computed by fitting the model equations to the myocardial regional time-activity curve. For the bolus injection of 15O-water, only two parameters, MBF and PTF, were fitted by using a fixed Va value obtained by a carbon dioxide blood volume scan. RESULTS: All protocols provided consistent MBF values, and the calculated values were homogeneous throughout the whole myocardial segments for all subjects. PTF values were also homogeneous and consistent in the anterior and lateral wall regions, but were significantly greater in the septum (approximately 20%) when the slow 15O-carbon dioxide inhalation protocol was used. MBF and PTF values obtained from the bolus injection protocol showed the smallest intersubject and interregional variations. The simulation study also showed that the magnitude of error was smallest when the bolus injection protocol was employed. CONCLUSION: The data suggest that the 15O-water bolus injection protocol together with the two-parameter fitting procedure provides the most accurate results for MBF and PTF. However, it requires arterial cannulation and a separate carbon monoxide scan. For clinical studies, however, the 15O-water infusion protocol would be a good alternative, providing MBF and PTF results with an acceptable degree of accuracy and without the need for arterial cannulation.

Administration, Inhalation↗

PubMed1994

The MID2 gene encodes a putative integral membrane protein with a Ca(2+)-binding domain and shows mating pheromone-stimulated expression in Saccharomyces cerevisiae.

The MID2 gene whose defect (the mid2-1 mutation) results in mating-pheromone-induced death in Saccharomyces cerevisiae was cloned and its nucleotide (nt) sequence determined. The sequence showed an open reading frame (ORF) coding for a 376-amino-acid (aa) protein with an estimated M(r) of 39,104, and six potential TATA boxes and two pheromone-response elements in its 5'-upstream region. The deduced aa sequence showed that the MID2 product (Mid2p) contains a putative N-terminal signal sequence followed by a long Ser-rich region that could contain O-glycosylation sites, a potential transmembrane domain and a conserved Ca(2+)-binding domain, with the latter two located in the C-terminal half. Northern blot analysis showed that the expression of MID2 is stimulated threefold by mating pheromone. Cells that lack MID2 were able to grow normally, but died when exposed to mating pheromone, like the original mid2-1 mutant.

Amino Acid Sequence↗

PubMed1994

Spinal cord intramedullary pressure. A possible factor in syrinx growth.

STUDY DESIGN: This study analyzed biomechanical characteristics of the cervical spinal cord, especially in relation to neck flexion. Intramedullary pressure was measured in different neck positions. OBJECTIVES: The results provided a rationale for dynamic changes in intramedullary pressure, with the flexed neck position playing a role in syrinx growth. SUMMARY OF BACKGROUND DATA: Dynamic changes in intramedullary pressure in the flexed position have been postulated to play an important role in syrinx growth. However, intramedullary pressure of the spinal cord has not been measured. METHODS: The authors designed a balloon method to assess, experimentally, intramedullary pressure dynamics of the spinal cord. A system was incorporated to examine the reliability of the balloons. Using 15 mongrel dogs, two balloons were embedded in the cervical spinal cord. Intramedullary pressure of the spinal cord was measured in several neck positions. In 5 of them, the same measurements were repeated when the spinal cord and roots were transected. RESULTS: When filled with a suitable volume of water, the balloons faithfully transmitted the pressure of the environment. No pressure differences were observed with the neck in the extended or neutral positions. However, when the neck was flexed, intramedullary pressure significantly increased. This increase in intramedullary pressure in the flexed neck position was not observed after spinal cord and roots were transected. CONCLUSION: The results indicated that the intramedullary pressure of the cervical spinal cord increases when the neck is flexed. This phenomenon might play an important role in syrinx growth.

Animals↗

PubMed1994

Roles of the carboxy-terminal region of Clostridium perfringens alpha toxin.

Treatment of Clostridium perfringens alpha toxin with aminopeptidase resulted in no effect on various activities of the toxin. Aminopeptidase did not hydrolyze the native toxin or the toxin treated with urea in the presence of EDTA. Treatment with carboxypeptidase for 30 min resulted in a 75% decrease in these activities. Incubation of the native toxin with carboxypeptidase for 30 min released approximately 15 amino acids from the C-terminus of the toxin. The biological activities of a mutant toxin lacking 20 C-terminal residues of the toxin (AT1-350) showed about 59-87% of the activity of native toxin. The mutant toxin showed partial antigenic identity with the native toxin. These data suggest that the C-terminal domain contributes to maintaining the active form of the toxin.

Aminopeptidases↗

PubMed1994

Secretion of human intracellular aspartic proteinase cathepsin E expressed in the methylotrophic yeast, Pichia pastoris and characterization of produced recombinant cathepsin E.

The human gastric cathepsin E (CTSE), a dimeric aspartic proteinase, was expressed in the methylotrophic yeast Pichia pastoris by placing the CTSE cDNA under the control of the methanol inducible alcohol oxidase promoter. The human CTSE expressed in P. pastoris was secreted into the culture medium as an active enzyme directed by its native signal sequence despite its intracellular localization in mammalian cells. The time course analysis of the culture supernatant of the P. pastoris transformant expressing human CTSE revealed that the recombinant human CTSE was secreted as a 90 kDa molecule and then converted via an 84 kDa intermediate to an 82 kDa mature molecule. A large-scale culture of the transformant was performed in a high cell density fermentor and the recombinant human CTSE was highly purified from the culture supernatant. The purified recombinant cathepsin E had the molecular mass of 82 kDa with the amino-terminal sequence starting with Ile37 of the sequence deduced from its cDNA sequence, suggesting that the human cathepsin E was accumulated in the culture supernatant as mature dimeric enzyme. The result of endoglycosidase-H digestion followed by Western blot analysis of the purified recombinant cathepsin E suggested that the human cathepsin E expressed in P. pastoris received N-linked high-mannose type glycosylation. The enzymatic properties of the recombinant enzyme were comparable to those of natural human CTSE.

Base Sequence↗

PubMed1994

Intracellular free calcium level and its response to cAMP stimulation in developing Dictyostelium cells transformed with jellyfish apoaequorin cDNA.

A new method is described for measuring intracellular free calcium concentrations, [(Ca2+)i], in the cells of Dictyostelium discoideum transformed with apoaequorin cDNA of the jellyfish, Aequorea victoria. Aequorin, a calcium-specific indicator, was regenerated in vivo from apoaequorin produced in the cells by incubation with coelenterazine. The results showed that [(Ca2+)i] in developing cells markedly increases at the aggregation stage and again at the culmination stage after a temporary drop at the migration stage. Except for the vegetative stage, the cells at all stages of development exhibit a sharp transient increase in [(Ca2+)i] upon stimulation with a cAMP (50 nM) pulse, high responses being observed at the migration and culmination stages. Separated prestalk cells of migrating slugs contain more than twice as much [(Ca2+)i] and show three times as large a response to cAMP stimulation as prespore cells.

Aequorin↗

PubMed1994

A method to quantitate cerebral blood flow using a rotating gamma camera and iodine-123 iodoamphetamine with one blood sampling.

A method has been developed to quantitate regional cerebral blood blow (rCBF) using iodine-123-labelled N-isopropyl-p-iodoamphetamine (IMP). This technique requires only two single-photon emission tomography (SPET) scans and one blood sample. Based on a two-compartment model, radioactivity concentrations in the brain for each scan time (early: t(e); delayed: td are described as: [formula: see text] respectively, where x denotes the convolution integral; Ca(t), the arterial input function; f, rCBF; and Vd, the regional distribution volume of IMP. Calculation of the ratio of the above two equations and a "table look-up" procedure yield a unique pair of rCBF and Vd for each region of interest (ROI). A standard input function has been generated by combining the input functions from 12 independent studies prior to this work to avoid frequent arterial blood sampling, and one blood sample is taken at 10 min following IMP administration for calibration of the standard arterial input function. This calibration time was determined such that the integration of the first 40 min of the calibrated, combined input function agreed best with those from 12 individual input functions (the difference was 5.3% on average). This method was applied to eight subjects (two normals and six patients with cerebral infarction), and yielded rCBF values which agreed well with those obtained by a positron emission tomography H2(15)O autoradiography method. This method was also found to provide rCBF values that were consistent with those obtained by the non-linear least squares fitting technique and those obtained by conventional microsphere model analysis. The optimum SPET scan times were found to be 40 and 180 min for the early and delayed scans, respectively. These scan times allow the use of a conventional rotating gamma camera for clinical purposes. Vd values ranged between 10 and 40 ml/g depending on the pathological condition, thereby suggesting the importance of measuring Vd for each ROI. In conclusion, optimization of the blood sampling time and the scanning time enabled quantitative measurement of rCBF with two SPET scans and one blood sample.

Aged↗

PubMed1994

Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction.

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)]fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.

Aged↗

PubMed1994

Prevalence of Lyme borrelia in ticks, especially Ixodes persulcatus (Acari: Ixodidae), in central and western Japan.

Prevalence of Lyme Borrelia in unfed ticks was surveyed in central and western Japan during spring from 1991 to 1993. The tick fauna was diverse; ticks obtained consisted of four genera and more than 12 identified species, and both southern and northern species coexist with altitudinal separation. Midguts of ticks were cultured in BSK medium for spirochetal isolation. Borrelia-positive rates for adults of both a common species, Ixodes ovatus Neumann, and a northern species, Ixodes persulcatus Schulze, in the extreme western part of the Japanese central mountainous zone (Fukui and Gifu prefectures) were 18.1 and 12.9%, respectively. A Borrelia-positive nymph of Haemaphysalis flava Neumann also was found for the first time in Japan. In contrast, I. persulcatus in southwestern Japan was localized in mountains with elevations over 800 m and was determined negative for Borrelia, whereas I. ovatus was highly positive (28.8%). These Borrelia isolates were diverse in typing of protein profiles. Our results reveal that I. persulcatus-borne Borrelia derived from northern Japan is kept within the limits of the western extremity of the central mountainous zone.

Animals↗

PubMed1994

MID1, a novel Saccharomyces cerevisiae gene encoding a plasma membrane protein, is required for Ca2+ influx and mating.

By establishing a unique screening method, we have isolated yeast mutants that die only after differentiating into cells with a mating projection, and some of them are also defective in Ca2+ signaling. The mutants were classified into five complementation groups, one of which we studied extensively. This mutation defines a new gene, designated MID1, which encodes an N-glycosylated, integral plasma membrane protein with 548 amino acid residues. The mid1-1 mutant has low Ca2+ uptake activity, loses viability after receiving mating pheromones, and escapes death when incubated with high concentrations of CaCl2. The MID1 gene is nonessential for vegetative growth. The efficiency of mating between MATa mid1-1 and MAT alpha mid1-1 cells is low. These results demonstrate that MID1 is required for Ca2+ influx and mating.

Amino Acid Sequence↗

PubMed1994

Fetal responses to acute fetal cocaine injection in sheep.

Maternal cocaine injection causes fetal hypoxemia, hypertension, and increased cerebral blood flow (CBF) in sheep. To test the hypothesis that increased fetal CBF is not due solely to fetal hypoxemia, we injected cocaine directly into a fetal vein. A single dose of cocaine [1 (group 1; n = 7) or 2 (group 2; n = 8) mg/kg i.v.] was administered to chronically catheterized, unanesthetized, near-term fetal sheep. Fetal CBF (microspheres), arterial blood pressure (BP), O2 content, and cerebral O2 consumption (CMRo2) were measured at baseline, 30 s, and 2, 5, and 15 min after fetal cocaine injection. Fetal CBF increased 27 +/- 9% (SE) at 5 min in group 1 and returned to baseline by 15 min, whereas fetal CBF increased 57 +/- 8% at 5 min and remained elevated at 15 min in group 2. Fetal BP increased at 30 min in both groups and remained increased at 2 min in group 1 and at 5 min in group 2. Cerebrovascular resistance increased at 30 s in both groups and then decreased at 5 min only in group 2. Fetal hypoxemia was observed in group 2 5 min after cocaine injection (arterial PO2 decreased 24 +/- 5%), whereas no hypoxemia was noted in group 1. CMRO2 was unchanged in group 1 but increased in group 2 at 5 min (41 +/- 10%) and was associated with an increase in cerebral O2 extraction. Increases in myocardial and adrenal blood flows and reductions in both small and large intestinal blood flows were noted at 5 min in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Effects of erythropoietin treatment on thyroid dysfunction in hemodialysis patients with renal anemia.

The thyroid function was evaluated before and after 6 months of recombinant human erythropoietin (rhEPO) treatment (1,500-9,000 U/week) in 22 hemodialysis patients with hematocrit levels < 25%. Based upon the changes in hematocrit following rhEPO treatment, the patients were divided into two groups: 11 patients with an increase of the hematocrit level > 5% (group I) and 11 patients with an increase < 5% (group II). Before rhEPO administration, the levels of thyroid hormones, especially free thyroxine (T4) and free triiodothyronine (T3), were below the normal range despite normal thyrotropin values in most of the patients (low T4:7 cases in group I and 9 in group II; low T3:10 cases in group I and 10 in group II). RhEPO treatment significantly increased both total amount and free fractions of thyroid hormones in group I, whereas it did not affect these values in group II. Consequently, the pretreatment low T4 or low T3 status was resolved in a substantial number of the patients in group I (low T4:5 cases, low T3:4 cases). In addition, there was a significant correlation between the increases in hematocrit and free T3 in all studied subjects (r = 0.603; p < 0.05). These results suggest that anemia may participate to some extent in the pathogenesis of thyroid dysfunction in hemodialysis patients with renal anemia.

Adult↗

PubMed1994

Phasic secretion of newly synthesized atrial natriuretic factor from unstimulated atrial myocytes in culture.

We have examined kinetics and composition of newly synthesized proteins secreted from cultured atrial myocytes from adult rats. Under unstimulated conditions, noncontracting cultured atrial myocytes, which were pulse-labeled for 10 minutes with [35S]methionine, rapidly released a considerable portion of newly synthesized atrial natriuretic factor (ANF) in a phasic secretion with a peak at 40 to 80 minutes of chase time. The phasic secretion almost ceased after 80 minutes of chase, after which relatively slow release of the hormone was observed. The ability to stimulate the phasic secretion with secretagogues and a marked resemblance of the radiochemical composition of released proteins in the unstimulated phasic secretion to that in stimulated secretion suggest that the proteins discharged from the cells during the phasic secretion might be derived from secretory granules. Examination of the quantitative change of intracellular ANF showed that approximately 60% of newly synthesized labeled ANF was still retained in the cells after the termination of the phasic secretion, indicating that the termination of the phasic secretion was not due to depletion of the labeled protein in the cells. These results suggest that a proportion of newly synthesized ANF was rapidly released from the unstimulated atrial myocytes via a secretory route that shares certain features with both the regulated and the constitutive secretory pathway and that a part of newly synthesized ANF is processed for rapid release while the remainder is destined for slow release or storage within the cells.

Amino Acid Sequence↗

PubMed1994

Mechanisms of vasodilation of cerebral vessels induced by the potassium channel opener nicorandil in canine in vivo experiments.

BACKGROUND AND PURPOSE: Nicorandil, a potent antianginal agent characterized as a potassium channel opener, could produce cerebrovascular dilation in in vitro studies. Our aim was to investigate the pharmacologic response to the topical application of nicorandil on the vasomotor tone of pial vessels in vivo. To elucidate its mechanism, we also studied the inhibitory action of methylene blue and glibenclamide against nicorandil-induced vasodilation. METHODS: In 14 dogs prepared with a parietal cranial window, we administered five different concentrations of nicorandil solution (10(-7), 10(-6), 10(-5), 10(-4), and 10(-3) mol/L) under the window and measured pial arterial and venular diameters. After pretreating pial vessels with either 10(-5) mol/L methylene blue or 10(-5) mol/L glibenclamide, we examined inhibitory action after the application of 10(-5) mol/L nicorandil. In additional experiments with 9 dogs, we evaluated the effects of nitroglycerin and cromakalim on pial vessels in the absence or presence of 10(-5) mol/L methylene blue and 10(-5) mol/L glibenclamide, respectively. RESULTS: Nicorandil produced significant, concentration-dependent dilation of pial vessels (P < .05). Methylene blue blocked nicorandil-induced dilation, whereas glibenclamide only attenuated such action of nicorandil. Nitroglycerin and cromakalim also produced a concentration-dependent increase in pial arteriolar and venular diameters (P < .05), and those effects were blocked in the presence of methylene blue or glibenclamide, respectively. CONCLUSIONS: Our in vivo study demonstrates that topical application of nicorandil dilates both pial arterioles and venules in a concentration-dependent manner and suggests that the mechanisms of such actions are most likely due to both cyclic GMP-mediated vascular smooth muscle dilation and the regulation of K+ flux.

Administration, Topical↗