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Biomedical subjects

H Iida

Publications and source records attributed to H Iida.

At least 37 records · Page 2Linked to original sources

Age-related decreases in the response of aquaporin-5 to acetylcholine in rat parotid glands.

Aquaporin-5 (AQP5) is important in salivary fluid secretion in response to cholinergic and adrenergic stimuli in rat parotid glands. We hypothesized that expression and function of AQP5 might change with age. Acetylcholine and epinephrine induced increases in AQP5 levels in the apical plasma membranes of both young adult and senescent rats. The stimulatory effect of acetylcholine, but not that of epinephrine, on AQP5 levels in the apical plasma membranes of the cells decreased markedly during aging. The quinuclidine derivative, SNI-2011, induced a persistent increase in AQP5 levels in the apical plasma membrane in the cells of both these rats. The amounts of M(3)-muscarinic receptor and Gq proteins did not decrease during aging. The age-related alteration in the responsiveness of AQP5 in the cells to these stimuli might account for the concomitant changes in nitric oxide synthase activity. These results suggest that SNI-2011 might have therapeutic benefit for the treatment of age-related xerostomia.

Acetylcholine↗

Mating-induced cumulus-oocyte maturation in the shrew, Suncus murinus.

The musk shrew, Suncus murinus, is an induced ovulator, the cumulus oophorus of which is unusual in several respects: it has no matrix, it always induces the acrosome reaction and it appears to be essential for fertilization. The present study documents distinctive features of the cumulus oophorus before and after ovulation, and of copulation-induced maturation of the ovulatory follicle, which has no antrum. In unmated females, potentially responsive ovarian follicles are distinguishable from large secondary follicles by differentiation of the granulosa into outer and inner cell layers, the latter being characterized particularly by intracellular glycogen deposits. The average number of responsive follicles equates with the number that ovulate. By about 10 h after mating, meiosis has reached metaphase II, with extrusion of the first polar body. Coincidentally, a cavity has developed between the inner and outer follicular layers, demarcating the smaller cells of the granulosa from the glycogen-rich cells of the cumulus oophorus. Subsequently, the glycogen becomes restricted primarily to the inner cumulus, and the corona cells began to retreat from the zona pellucida surface to form an unusual very distinct perizonal space that is clearly evident at the time of ovulation. The cumulus is stabilized by gap and tight junctions, and presents a smooth external surface that appears to initiate the acrosome reaction. After fertilization, at which time the zona pellucida becomes more resistant to both trypsin and dithiothreitol, the cumulus develops intercellular lacunae, and is eventually discarded about 15 h after ovulation.

Acrosome Reaction↗

Genetic relatedness among Japanese, American and European isolates of viral hemorrhagic septicemia virus (VHSV) based on partial G and P genes.

Molecular virological analyses of 8 Japanese VHSV (viral hemorrhagic septicemia virus) isolates from wild and farmed Japanese flounder Paralichthys olivaceus were performed to investigate their genetic relatedness to American and European isolates of VHSV. Phylogenetic analyses based on the partial nucleotide sequences of G and P genes revealed that there are 2 genogroups of VHSV in Japan. The first one represented by the Obama25 isolate is closely related to the American isolates (Genogroup I) while the other, the KRRV9601 isolate, is closely related to the traditional European isolates (Genogroup III). The 2 types of Japanese VHSV showed differences in the relative mobility of the G protein and intensity of the antibody reaction on the P and M proteins. The Obama25 type of VHSV is widely distributed as a native virus in the coastal areas of western Japan and has been responsible for the occurrence of VHSV infection in farmed Japanese flounder while the KRRV9601 isolate is considered to have been introduced from a foreign country.

Animals↗

A test model of hip brace for prevention of dislocation after total hip arthroplasty (Zetton Band).

Hip dislocations remain an intractable problem in patients with soft tissue impairment, particularly in those with muscle weakness around the hip, such as those who have undergone revision total hip arthroplasty (THA). At the authors' hospital, postoperative dislocations were observed in 10 of 154 hips between January 1985 and June 1988. Five hips required re-replacement. Conventional measures to prevent or treat post-THA dislocations have been anti-dislocation pants for soft fixation and a cast or abduction-forcing braces for firm fixation. However, the anti-dislocation pants for soft fixation were not as effective as indicated by the above 10 postoperative dislocations. The firm fixation techniques are considered to cause a reduction in muscle strength, causing psychological stress and poor activity of daily living (ADL). The authors devised a soft brace for easy application and prepared its test model to prevent muscle weakening, allow stability of the hip during rotation and avoid restrictions in ADL. This brace was applied to a patient who had 3 dislocations in a short period after being discharged who sustained a postoperative dislocation and achieved good results.

Aged↗

The modified Spitzy shelf operation for patients with dysplasia of the hip. A 24-year follow-up study.

We evaluated the long-term results of a modified Spitzy shelf operation for secondary osteoarthritis in 119 hips with a mean follow-up of 23.8 years. The mean age of the patients at the time of surgery was 25 years. Preoperative osteoarthritic change, the age at operation and shelf height were important factors in determining the outcome. Of the 61 hips in the pre-stage (three) and the initial stage (58) of osteoarthritis, 53 (87%) had good results, compared with only 30 (51%) of 58 hips with advanced osteoarthritis. Of the latter, 72% of those aged less than 25 years had good results compared with only 40% of patients aged over 25 years. The shelf height in the group with good results was significantly lower than in those with poor results. This operation is a safe procedure and indicated for acetabular dysplasia or subluxation of the hip with early osteoarthritic change in patients aged less than 25 years.

Acetabulum↗

Intra-bone marrow injection of allogeneic bone marrow cells: a powerful new strategy for treatment of intractable autoimmune diseases in MRL/lpr mice.

Intractable autoimmune diseases in chimeric resistant MRL/lpr mice were treated by a new bone marrow transplantation (BMT) method consisting of fractionated irradiation, 5.5 Gy x 2, followed by intra-bone marrow (IBM) injection of whole bone marrow cells (BMCs) from allogeneic normal C57BL/6 (B6) mice (5.5 Gy x 2 + IBM). In MRL/lpr mice treated with this method, the number of donor-derived cells in the bone marrow, spleen, and liver rapidly increased (almost 100% donor-derived cells by 14 days after the treatment), and the number of donor-derived hemopoietic progenitor cells concomitantly increased. Furthermore, donor-derived stromal cells were clearly detected in the cultured bone pieces from MRL/lpr mice treated with 5.5 Gy x 2 + IBM. All the recipients thus treated survived more than 1 year (> 60 weeks after birth) and remained free from autoimmune diseases. Autoantibodies decreased to almost normal levels, and abnormal T cells (Thy1.2(+)/B220(+)/CD4(-)/CD8(-)) disappeared. Hematolymphoid cells were reconstituted with donor-derived cells, and newly developed T cells were tolerant to both donor (B6)-type and host (MRL/lpr)-type major histocompatibility complex determinants. Successful cooperation was achieved among T cells, B cells, and antigen-presenting cells when evaluated by in vitro antisheep red blood cell responses. These findings clearly indicate that this new strategy (IBM-BMT) creates the appropriate hemopoietic environment for the early recovery of hemopoiesis and donor cell engraftment, resulting in the complete amelioration of intractable autoimmune diseases in chimeric resistant MRL/lpr mice without recourse to immunosuppressants. This strategy would therefore be suitable for human therapy.

Animals↗

Failure in the detection of aberrant mRNA from the heterozygotic splice site mutant allele for protein S in a patient with protein S deficiency.

A 29-year-old male patient with acute arterial obstruction and a medical history including thrombosis in the deep veins and pulmonary infarction presented with a reduced level of both protein S (PS) activity and free PS. Sequencing of the genomic PS gene in this patient revealed that the patient was heterozygous for the mutant PS allele, in which a nucleotide substitution occurred at the donor splice site in intron 12 (GT to GA). The patient was heterozygous for PS genes having dimorphic codons for Pro626 (CCA/CCG) and the aberrant allele in this patient was associated with the CCA form. Allelic exclusion of PS expression was demonstrated by use of Pro626 (CCA/CCG) dimorphism and only a normal mRNA sequence derived from the CCG-allele was identified in the patient. These findings suggested that the mutation at the splice site in the PS gene caused either defective production of mRNA or the gene may have produced extremely unstable RNA products, leading to reduced levels of PS activity and free PS in this patient.

Adult↗

Purification, characterization, molecular cloning, and subcellular distribution of neutral ceramidase of rat kidney.

Previously, we reported two types of neutral ceramidase in mice, one solubilized by freeze-thawing and one not. The former was purified as a 94-kDa protein from mouse liver, and cloned (Tani, M., Okino, N., Mori, K., Tanigawa, T., Izu, H., and Ito, M. (2000) J. Biol. Chem. 275, 11229--11234). In this paper, we describe the purification, molecular cloning, and subcellular distribution of a 112-kDa membrane-bound neutral ceramidase of rat kidney, which was completely insoluble by freeze-thawing. The open reading frame of the enzyme encoded a polypeptide of 761 amino acids having nine putative N-glycosylation sites and one possible transmembrane domain. In the ceramidase overexpressing HEK293 cells, 133-kDa (Golgi-form) and 113-kDa (endoplasmic reticulum-form) Myc-tagged ceramidases were detected, whereas these two proteins were converted to a 87-kDa protein concomitantly with loss of activity when expressed in the presence of tunicamycin, indicating that the N-glycosylation process is indispensable for the expression of the enzyme activity. Immunohistochemical analysis clearly showed that the ceramidase was mainly localized at the apical membrane of proximal tubules, distal tubules, and collecting ducts in rat kidney, while in liver the enzyme was distributed with endosome-like organelles in hepatocytes. Interestingly, the kidney ceramidase was found to be enriched in the raft microdomains with cholesterol and GM1 ganglioside.

Amidohydrolases↗

A novel splice acceptor site mutation of protein S gene in affected individuals with type I protein S deficiency: allelic exclusion of the mutant gene.

Sequencing studies of the protein S gene (PROS1) in a Japanese patient suffering from recurrent thrombosis revealed the following. The proband and his first daughter, but not the second daughter, were having the type I protein S (PS) deficiency due to a novel point mutation from A to G at the intronic acceptor splice site in intron 13 of the PROS1. In the affected daughter, exclusion of the aberrant allele was assessed by the BstX1 dimorphism of PROS1 at Pro626 (CCG/CCA). The reduced PS activities in the proband and his first daughter were apparently due to defective production of mRNA from the mutant allele.

Alleles↗

Arterial fraction of cerebral blood volume in humans measured by positron emission tomography.

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.

Adult↗

Brain perfusion SPECT study with 99mTc-bicisate: clinical pitfalls and improved diagnostic accuracy with a combination of linearization and scatter-attenuation correction.

To evaluate the usefulness of a combination of linearization and scatter-attenuation correction on 99mTc-bicisate (ECD)-single photon emission tomographic (SPECT) images, both cerebral blood flow (CBF)-positron emission tomographic (PET) images and ECD-SPECT images from fifteen patients with chronic cerebral infarction were acquired. We measured radioactivity counts in regions of interest (ROIs) on all sets of both images and obtained a 2D scattered graph between ECD-SPECT and CBF-PET data. To evaluate diagnostic accuracy, the sensitivity, specificity and accuracy of ECD-SPECT images were calculated by means of discriminant analysis. The same analysis was also performed on the ECD-SPECT images corrected by a combination of linearization and scatter-attenuation correction. An overall nonlinear relationship was observed between ECD-SPECT and CBF-PET. The sensitivity, specificity, and accuracy of ECD-SPECT images were 69.6%, 91.4% and 73.0%, and those of ECD images corrected by the combination of linearization and scatter-attenuation correction were 79.5%, 95.7% and 82.0% respectively. The clinically diagnostic accuracy of ECD-SPECT images corrected by the combined method apparently increased. So that the linearization with the scatter-attenuation method is useful for improving the diagnostic accuracy of ECD-SPECT images.

Aged↗

Use of [11C]acetate and [15O]O2 PET for the assessment of myocardial oxygen utilization in patients with chronic myocardial infarction.

Carbon-11 acetate positron emission tomography (PET) has been widely used to assess regional oxidative metabolism of the heart. However, the accuracy of [11C]acetate PET in assessing oxidative metabolism in infarcted myocardium remains controversial. Thirteen patients with stable coronary artery disease and old myocardial infarction were studied. The 15O-based PET studies yielded regional blood flow (rMBF, ml/min/g) and oxygen consumption (rMMRO2, ml/min/g), which was compared with the myocardial clearance rate constant (kmono) of [11C]acetate in segments with rMBF > or = 75% (group A), 50%-74% (group B) or < 50% (group C) of the normal reference segment. Mean MBF was 0.96 +/- 0.08 ml/g/min in group A, 0.67 +/- 0.06 ml/g/min in group B and 0.42 +/- 0.07 ml/g/min in group C segments. The segmental rMMRO2 correlated linearly with kmono (r = 0.89, P < 0.001, y = 0.61x + 0.026). The kmono/rMMRO2 ratio was comparable in the group A and B segments (0.99 +/- 0.19 vs 1.07 +/- 0.21, P = NS). However, the ratio was significantly higher in the group C segments (1.28 +/- 0.35, P = 0.037). It is concluded that kmono of [11C]acetate correlates linearly with rMMRO2 determined by [15O]O2 inhalation. However, kmono appears to yield higher rMMRO2 estimates than the [15O]O2 method in low-flow areas.

Acetates↗

Reduced myocardial flow reserve relates to increased carotid intima-media thickness in healthy young men.

Increased carotid artery wall thickness and lipoprotein oxidation are key early events in atherosclerosis. To test the hypothesis that reduced myocardial flow reserve is a marker of subclinical atherosclerosis, we examined the relationships between flow reserve and carotid artery intima-media thickness (IMT) in young men free from coronary heart disease. Basal and dipyridamole stimulated coronary blood flow was measured using positron emission tomography (PET) in 55 healthy men aged 36+/-4 years. Myocardial flow reserve was calculated as the ratio of stimulated flow to basal flow. The mean carotid artery IMT was measured using high-resolution ultrasound. Oxidised LDL was measured as baseline LDL diene conjugation. Myocardial flow reserve decreased across the quartiles of increasing IMT (P=0.006), and was 5.2+/-1.9 in the lowest quartile for IMT and 3.7+/-1.2 in the highest (P=0.04, I vs. IV quartile). In univariate analysis, oxidised LDL correlated inversely with flow reserve (r=-0.35, P=0.01) and directly with IMT (r=0.51, P<0.001). The association between flow reserve and IMT remained significant (P< or =0.01) in multivariate regression model including age, blood pressure, left ventricular mass, ox-LDL, total cholesterol, HDL-cholesterol and triglycerides as covariates. These data support the concept that reduced myocardial flow reserve reflects subclinical atherosclerosis in asymptomatic subjects, and suggest that increased lipoprotein oxidation is directly related to early structural and functional atherosclerotic vascular changes.

Adult↗

Comparison of myocardial blood flow during dobutamine-atropine infusion with that after dipyridamole administration in normal men.

OBJECTIVES: The present study was designed to compare the absolute myocardial blood flow (MBF) after intravenous dipyridamole infusion with that during dobutamine-atropine administration in normal healthy male volunteers. BACKGROUND: Both safety and usefulness of dobutamine-atropine stress in myocardial perfusion imaging have been reported. However, no information exists on whether the magnitude ofhyperemia achieved with dipyridamole and dobutamine-atropine is comparable. METHODS: Myocardial blood flow was measured with positron emission tomography and 15O-labeled water in 20 healthy young men (23 +/- 3 years) 1) at baseline, 2) after dipyridamole infusion (0.56 mg/kg over 4 min), and 3) during dobutamine (40 microg/kg/min) and atropine (0.25 to 1.0 mg) infusion. RESULTS: The MBF was significantly increased during dipyridamole infusion and during dobutamine-atropine stress compared with at rest (4.33 +/- 1.23 and 5.89 +/- 1.58 vs. 0.67 +/- 0.16 ml/min/g, respectively, p < 0.0001). Moreover, dobutamine-atropine infusion produced greater MBF compared with dipyridamole (p = 0.0011), while coronary vascular resistance did not differ significantly after dipyridamole administration and during dobutamine-atropine infusion (17.6 +/- 7.9 vs. 18.6 +/- 5.6 mm Hg/[ml/min/g], respectively). CONCLUSIONS: Near maximal coronary vasodilatation caused by dipyridamole is attainable using dobutamine and atropine in young healthy volunteers. Dobutamine in conjunction with atropine is no less effective than dipyridamole in producing myocardial hyperemia.

Adult↗

Ketamine, not propofol, attenuates cerebrovascular response to carbon dioxide in humans with isoflurane anesthesia.

STUDY OBJECTIVES: To investigate the effects of ketamine and propofol on the cerebrovascular response to carbon dioxide (CO(2)) in humans during isoflurane anesthesia. DESIGN: Randomized clinical investigation. SETTINGS: University hospital of a medical school. PATIENTS: 30 ASA physical status I and II adult, elective surgical patients. INTERVENTIONS AND MEASUREMENTS: With each patient given air/oxygen/isoflurane anesthesia, the flow velocity in the middle cerebral artery (Vmca) and pulsatility index were measured using the transcranial Doppler method under hypocapnic [arterial CO(2)tension (PaCO(2)) 28-32 mmHg], normocapnic (PaCO(2) 38-42 mmHg), and hypercapnic conditions (PaCO(2) 48-52 mmHg). PaCO(2) was altered by supplementing the inspired gas with CO(2) without changing the respiratory conditions. Patients were then randomly assigned to receive either ketamine 1 mg. kg(-1) or propofol (2 mg. kg(-1)followed by an infusion of 6-10 mg. kg(-1). hr(-1)) (n = 15 for each drug), and the measurements were repeated. MAIN RESULTS: Ketamine reduced both absolute and relative cerebrovascular reactivity to CO(2) significantly [2.9 +/- 0.8 (control) vs. 2.6 +/- 1.0 (ketamine) cm. sec(-1). mmHg(-1): p < 0.05; and 3.5 +/- 0.7 (control) vs. 2.8 +/- 0.9 (ketamine) %. mmHg(-1): p < 0.01, respectively]. However, ketamine did not reduce Vmca during hypercapnic conditions (117 +/- 29 cm. sec(-1)) compared with controls (120 +/- 28 cm. sec(-1)). Although propofol decreased Vmca during all conditions, it did not cause any change in either absolute or relative CO(2) reactivity [2.5 +/- 0.8 (control) vs. 2.5 +/- 1.0 (propofol) cm. sec(-1). mmHg(-1), and 3.3 +/- 1.3 (control) vs. 4.1 +/- 1.0 (propofol) %. mmHg(-1), respectively]. CONCLUSIONS: In humans given isoflurane anesthesia, a) ketamine reduced cerebrovascular response to CO(2), but cerebral blood flow (CBF) during hypercapnic conditions was comparable with controls, and b) although propofol decreases CBF, it maintains the cerebrovascular response to CO(2).

Adult↗

Effect of diltiazem on cardiac function assessed by echocardiography and neurohumoral factors after reperfused myocardial infarction without congestive heart failure.

The purpose of this study was to examine the effect of diltiazem on cardiac function and neurohumoral factors (BNP, epinephrine, norepinephrine) after reperfused myocardial infarction without congestive heart failure (Killip class I). On the first day after myocardial infarction following reperfusion therapy patients were randomly assigned to diltiazem treatment (group 1, n=33) or no treatment (group 2, n=39). We then performed echocardiographic examinations on the patients and measured heart rate, mean blood pressure and neurohormones (BNP, epinephrine and norepinephrine). Follow-up evaluations of echocardiography were performed at 4 and 12 weeks and of neurohormones at 1 and 4 weeks after acute myocardial infarction. The highest peaks of plasma BNP, epinephrine, and norepinephrine levels were observed before treatment and decreased with time in both groups. After 4 weeks the level of plasma BNP in the diltiazem treatment group was lower than in the no treatment group [55+/-3 pg/mL vs 85+/-5 pg/mL (P < 0.05)]. Other neurohormones did not differ between groups. Fractional shortening (FS) and ejection fraction (EF)improved after myocardial infarction in both groups, but significantly more in the diltiazem group (P < 0.05) after 12 weeks of treatment. Changes in BNP correlated significantly with changes in left ventricular end systolic volumes, FS and EF. In this study, diltiazem significantly improved systolic function and reduced the level of plasma BNP after myocardial infarction, which suggest that diltiazem may have a beneficial effect on myocardial infarction without congestive heart failure.

Aged↗