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Biomedical subjects

H Takeda

Publications and source records attributed to H Takeda.

At least 325 records · Page 18Linked to original sources

Specification of posterior midbrain region in zebrafish neuroepithelium.

BACKGROUND: The developing vertebrate nervous system displays a pronounced anterior-posterior (A-P) pattern, but the mechanism that generates this pattern is poorly understood. We examined through cell-transplantation experiments, when and how the cells in the zebrafish posterior midbrain acquire regional specificity along the A-P axis as shown by pax[b] gene expression. RESULTS: Labelled donor cells from the presumptive midbrain region at various stages were transplanted into more anterior part of unlabelled host embryos of the same developmental stage, and the expression of pax[b] in the donor cells were examined by in situ hybridization. The results indicated that, in the cells from the presumptive midbrain region, expression of pax[b] was determined as early as the 55%-epiboly (6.5 h, early gastrulation) when the underlying hypoblastic layer reached the presumptive midbrain region. We also found that when transplanted heterotopically, anterior, but not posterior, hypoblast cells induced expression of pax[b] in the overlying ectoderm. CONCLUSIONS: Expression of a midbrain specific gene is determined during early gastrulation and the hypoblastic layer plays an important role in this determination process.

Animals↗

Atrophic changes of gastric mucosa are caused by Helicobacter pylori infection rather than aging: studies in asymptomatic Japanese adults.

BACKGROUND: The current study was designed to evaluate the effect of aging and Helicobacter pylori infection on the gastric mucosa in asymptomatic Japanese adults. MATERIALS AND METHODS: Eighty-five asymptomatic healthy adults were recruited from a health-screening center in Sapporo. All subjects underwent endoscopy and gastric biopsy, and serum was obtained for IgG antibodies to H. pylori, serum gastrin, and pepsinogen levels. RESULTS: The prevalence of atrophic change of the gastric mucosa assessed by pathological findings increased with age (49% in the 30- to 39-year-old group compared to 89% in those 60 years and older, p < .001). The frequency of intestinal metaplasia also increased with age (38% in the 30- to 39-year-old group compared to 82% in those 60 years and older, p < .001). In contrast, the frequency of atrophic gastritis and intestinal metaplasia was extremely low in the H. pylori seronegative group regardless of age. Mean serum gastrin level in H. pylori-positive adults was significantly greater than in those who were H. pylori-negative (114.3 +/- 11.2 compared to 65.8 +/- 6.5 pg/ml, p < .03). The serum pepsinogen I-II ratio was significantly lower in those with H. pylori infection than in those without (3.1 compared to 6.6, p < .0001). CONCLUSIONS: These results suggest that the chronological changes in the gastric mucosa in Japanese individuals are either entirely related to H. pylori infection or the process is greatly accelerated by H. pylori infection.

Adult↗

Extracting 1/f fluctuation from the arterial blood pressure of an artificial heart.

We have studied the fluctuations of an artificial circulation for the analysis of the physiological aspects; however, the conventionally used fast Fourier transform (FFT) method cannot separate harmonic oscillations, such as respiratory and Mayer waves, from the 1/f fluctuation, which has been though to represent underlying fractal dynamics. Fractal structure was shown in the strange attractor with chaotic dynamics, which is thought to be a flexible and intelligent system. In this study, the coarse-graining spectral analyzing (CGSA) method was utilized to quantitatively evaluate the proportion of the 1/f fluctuation in the total power in the frequency domain and to analyze artificial circulation in the whole system. We implanted two pneumatically actuated ventricular assist devices as biventricular bypasses (BVBs) in chronic animal experiments using 4 healthy adult goats. To compare the natural and prosthetic circulation of each experimental animal, the BVB-type complete prosthetic circulation model with electrically induced ventricular fibrillation was adopted. All hemodynamic parameters of natural and prosthetic circulation were recorded under awake conditions and calculated with the use of a personal computer. With the use of the CGSA method, time-series data of the hemodynamics were analyzed and fractal percentages, extracting the 1/f fluctuation from a given time series, were calculated. Fractal percentages of the arterial blood pressure were 85.8 +/- 10.7% and 82.0 +/- 7.3% with natural and artificial circulation, respectively (not significant [NS]). 1/f fluctuation showed the characteristics of being fractal in a time series. The fractal structure showed robustness and error resistance in nonlinear dynamics. Therefore, our results suggest that the circulatory regulatory system of the artificial heart may have desirable characteristics such as error resistance.

Animals↗

Linkage of [Ca2+]i in single isolated D cells to somatostatin secretion induced by cholecystokinin.

The Ca2+/inositol phospholipid signaling cascade has been implicated in the mechanism by which cholecystokinin (CCK) stimulates gastric somatostatin release, but a direct linkage between intracellular events in gastric D cells and somatostatin secretion has not been established. To address this problem we developed a method for correlating somatostatin release with the measurement of intracellular Ca2+ concentration ([Ca2+]i) in isolated D cells. Resting [Ca2+]i in single D cells was 100 +/- 5.7 nM (means +/- SE, n = 41), and CCK induced a rise in [Ca2+]i in a dose-dependent fashion, producing a maximal stimulatory effect (243 +/- 15% of control, n = 12) at a peptide concentration of 2 x 10(-8) M. The CCK-mediated increase in [Ca2+]i was biphasic, with a rapid, initial transient elevation followed by a sustained plateau. The rise in [Ca2+]i was accompanied by a concomitant increase in release of somatostatin-like immunoreactivity (SLI). Removal of extracellular Ca2+ had no effect on the initial transient elevation in [Ca2+]i induced by CCK but abolished both the sustained plateau in [Ca2+]i and the release of SLI. The selective CCK antagonist L-364, 718 (10(-7) M) inhibited the effects of CCK on both [Ca2+]i and SLI release. The nonspecific Ca2+ channel blocker NiCl2 (10(-3) M) and the L-type Ca2+ channel blocker nifedipine inhibited the sustained rise in [Ca2+]i and the release of SLI but left the initial transient increase in [Ca2+]i unaltered. These results indicate that CCK-stimulated release of SLI from D cells in the gastric fundus is linked to influx of extracellular Ca2+ via L-type Ca2+ channels.

Animals↗

Effect of endotoxin on bile acid transport in rat liver: a potential model for sepsis-associated cholestasis.

Intrahepatic cholestasis in the setting of extrahepatic bacterial infection has been attributed to the effects of endotoxin and cytokines such as tumor necrosis factor-alpha (TNF-alpha) on bile acid transport. To define the mechanism of sepsis-associated cholestasis, taurocholate transport was examined in basolateral (bLPM) and canalicular (cLPM) rat liver plasma membrane vesicles derived from control and endotoxin [lipopolysaccharide (LPS)]-treated animals and in plasma membrane vesicles prepared after TNF-alpha treatment. Na(+)-dependent [3H]taurocholate uptake and both membrane-potential-dependent and ATP-dependent [3H]taurocholate transport were reduced in bLPM and cLPM vesicles, respectively, after LPS treatment. In membrane vesicles from TNF-alpha-treated animals, Na(+)-dependent [3H]taurocholate uptake was also reduced. Northern blot hybridization, using cDNA probes for the putative sinusoidal bile acid transporter (Ntcp) and canalicular ecto-adenosinetriphosphatase, demonstrated decreased mRNA levels after LPS and TNF-alpha treatment. Immunoblot analysis of membrane extracts from LPS-treated animals revealed decreased levels of these putative bile acid transporters. Impaired bile acid transport at the sinusoidal and canalicular membrane domains by these and other mediators of the inflammatory response may account for sepsis-associated cholestasis.

Adenosine Triphosphatases↗

Cardioprotection due to preconditioning correlates with increased ecto-5'-nucleotidase activity.

We investigated whether loss of myocardial protection after ischemic preconditioning (IP) is related to the extent of deactivation of activated ecto-5'-nucleotidase. The coronary arteries of mongrel dogs were occluded four times for 5 min separated by 5 min of reperfusion (IP). Five (IP1), 30 (IP2), 60 (IP3), and 120 min (IP4) after the fourth 5-min coronary occlusion or after a corresponding nonischemic period (control groups), the coronary arteries were occluded for 90 min followed by 6 h of reperfusion. The infarct size-limited effect of IP gradually disappeared in the IP2 (21.6 +/- 3.9%) and IP3 (33.8 +/- 3.6%) groups compared with the IP1 group (8.3 +/- 1.6%) and returned to the control level in the IP4 group (39.9 +/- 5.2%). The increased ecto-5' -nucleotidase activity due to the IP procedure decreased according to the order of IP1 to IP4 groups. Infarct size was inversely correlated with ecto-5'-nucleotidase activity (P < 0.001). An inhibitor of ecto-5'-nucleotidase blunted the infarct size-limiting effect of IP. The infarct size-limiting effect of IP decreased as the activation of ecto-5'-nucleotidase was blunted. These results suggest that ecto-5'-nucleotidase activity plays a key role in the cardioprotection of IP.

5'-Nucleotidase↗

Protective effects of Acanthopanax senticosus Harms from Hokkaido and its components on gastric ulcer in restrained cold water stressed rats.

The aim of this study is to investigate the pharmacological effect of the stem bark of Acanthopanax senticosus Harms from Hokkaido (Japanese name: Ezoukogi) in place of the root bark as a restorative tonic on the stress-induced gastric ulcer. In the test, the extract of the stem bark of A. senticosus prepared with hot water was dissolved in water and used for the assay of the protective effect of gastric ulcer (erosion) on stressed rats that were restrained on cold water. The result from a single oral administration of the stem bark of A. senticosus-extract (50, 100 and 500 mg/kg, per day) dissolved in 1 ml distilled water did not show any protective effect on gastric ulcer, but the protective effect was observed in a dose-dependent manner from the oral administration of the extract (50, 100 and 500 mg/kg, per day) for 2 weeks. Pre-administration of the stem bark of A. senticosus-extract in a dose of 500 mg/kg showed the most potent inhibition without affecting either body or adrenal glands weights. Among ether, chloroform, n-butanol and aqueous residue extracts from the stem bark of A. senticosus-extract, the n-butanol extract used for oral administration for 2 weeks showed an obvious inhibition of 61.1% on gastric ulcer, compared with the control group which was treated with distilled water in the same way. Chlorogenic acid and syringaresinol di-o-beta-D-glucoside, as the major components of the n-butanol extract, showed a significantly inhibitory effect on gastric ulcer, at 21.4% and 51.3%, respectively. We suggested that the protective effect of the stem bark of A. senticosus on gastric ulcer may be partially due to those of chlorogenic acid and syringaresinol di-o-beta-D-glucoside.

Adrenal Glands↗

[Behavioral studies of KSG-504, a new CCK-A receptor antagonist].

The effects of KSG-504 after intravenous administration on behavior and other central functions were studied. KSG-504 did not affect the general behavior of dogs up to the dose of 30 mg/kg, but the drug (100 mg/kg, i.v.) caused vomiting in 3 out of the 5 dogs. Moreover, KSG-504 (1-30 mg/kg, i.v.) had no effects on spontaneous motility, thiopental-induced sleep, acetic acid-induced writhing in mice and satiety in rats. A high dose of CCK-8 (100 micrograms/kg or more) suppressed spontaneous motility, writhing and satiety, and prolonged sleep when administered subcutaneously. The behavioral changes induced by CCK-8 were antagonized by KSG-504 in a dose-dependent manner (1-30 mg/kg, i.v.). When KSG-504 was administered intravenously to rabbits at the dose of 10 mg/kg or 0.5 mg/kg/min for 120 min, we could not detect the drug in the cerebrospinal fluid, indicating that KSG-504 does not cross the blood-brain barrier after peripheral administration of the drug. Thus, the inhibitory effect of KSG-504 on CCK-8-induced behavioral changes may be the result of antagonism at peripheral CCK-A receptors.

Animals↗

Effects of KSG-504, a new cholecystokinin-A-receptor antagonist, on pancreatic exocrine and endocrine secretions in rats.

The effects of KSG-504 ((S)-arginium (R)-4-[N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulf onyl) pentanoate monohydrate), a new cholecystokinin (CCK)-A-receptor antagonist, on pancreatic exocrine secretion in anesthetized rats and endocrine secretion in conscious rats were studied. Intravenous injection of KSG-504 inhibited the pancreatic amylase output stimulated by intravenous infusion of CCK-8 in a dose-dependent manner (ED50: 18 micrograms/kg/min). Moreover, KSG-504 significantly reduced the CCK-8-stimulated increases in pancreatic juice volume and outputs of protein, trypsin and lipase. Intraduodenal infusion of casein increased the plasma CCK concentration and the pancreatic amylase output. KSG-504 significantly inhibited the pancreatic amylase output stimulated by casein. Pancreatic juice volume and bicarbonate output were significantly stimulated by intravenous infusion of secretin, but were not changed by KSG-504. When pancreatic exocrine secretion was stimulated by secretin plus CCK-8, KSG-504 suppressed the increases in juice volume and bicarbonate output to the level stimulated by secretin alone. Basal pancreatic amylase output was decreased by KSG-504. KSG-504 decreased the level of plasma immunoreactive insulin (IRI) stimulated by glucose plus CCK-8, but had no effect on IRI stimulated by glucose alone and the basal IRI. These in vivo studies suggest that KSG-504 has significant inhibitory effects both on the pancreatic exocrine and endocrine secretion stimulated by CCK, but has no effect on the exocrine secretion stimulated by secretin.

Animals↗

Swift transformation and locomotion of polymorphonuclear leukocytes and microglia as observed by VEC-DIC microscopy (video microscopy).

The detailed assembly used by us for video-enhanced contrast-differential interference contrast (VEC-DIC) microscopy (video microscopy is first described. Employing such video microscopy, we then examined the morphological changes occurring during locomotion and activation processes of polymorphonuclear leukocytes (PMNL) and microglia at an almost electron microscopic magnification. Upon contacting the substratum, PMNL transformed into a polarized ameboid shape and crawled extending pseudopodia, as has been well documented previously. The PMNL sometimes displayed a peculiar locomotion as if they were stepping on "tiny legs", or sliding on a treadmill of cell membrane. Cultured microglia were observed to exist in 4 forms; ramified, reactive, villous, and ameboid. Microglia in the reactive form pivoted, circled and crawled on the astroglial cell layer using their transparent lamellipodia with no morphological changes in their cell body. Unlike PMNL, reactive microglia exhibited no agitated movements of their intracellular organelles, including granules and cytosol, during locomotion. Lamellipodia on the undersurface of the cell body touching the cell layer adhesively, appeared to serve as the locomotive apparatus. When activated, both floating PMNL and microglia of villous form assumed an ameboid shape within a few seconds. Microglia occasionally swam in the medium waving their lamellipodia towards a target object (e.g. zymosan A particles), remodelling to an amorphous ameboid form and covering up the target. We attempt to discuss such swift morphological changes from the standpoint of thermodynamic potential of Gibbs free energy which is stored within the cells.

Cell Movement↗

[Sound lateralization testing based on interaural intensity difference discrimination and interaural time difference discrimination in acoustic neurinoma patients--comparison of ABRS].

Sound lateralization is considered useful in diagnosing retrocochlear lesions. Interaural time difference (ITD) discrimination has been considered more important than interaural intensity difference (IID) discrimination in diagnosing retrocochlear lesions. The purpose of this study was to determine whether testing sound lateralization by IID and ITD discrimination is useful in patients with acoustic neurinomas (AN). Twenty patients (15 to 74 years old) with unilateral AN were studied by testing IID and ITD discrimination using a self-recording device by delivering 500 Hz band noise through head-phones. Auditory brainstem response (ABR) testing and magnetic resonance imaging (MRI) were also performed in all patients. IID discrimination abnormalities were found in 25% of all patients, and ITD discrimination abnormalities in 85%. Five patients (25%) showed both IID and ITD discrimination abnormalities. One of the three patients with both normal IID and ITD discrimination showed waves I and V, and two of them showed waves I, III and V. One of the five patients with both IID and ITD discrimination abnormalities showed no response, two of them showed only wave I, the other two showed waves I, III and V. Two patients with latency prolongation between waves III and V had both IID and ITD discrimination abnormalities, and seven patients with latency prolongation between waves I and III had normal ITD discrimination or slightly abnormal ITD discrimination and normal IID discrimination. Three of the four patients with large tumors (> 3 cm) had both IID and ITD discrimination abnormalities, while two patients with small ear tumors (< 1 cm) had both normal IID discrimination and normal ITD discrimination. Normal ITD discrimination or slightly abnormal ITD discrimination was found in the majority of patients with wave III. Impairment of ITD discrimination was well correlated with wave III abnormalities. Patients with latency prolongation between waves III and V showed a high degree of ITD discrimination abnormality. Impairment of IID discrimination was related to a high degree of cochlear nerve damage or brainstem damage. We emphasize that IID discrimination is important in the neurological diagnosis of AN, in addition to ITD discrimination. Sound lateralization testing was a useful screening test for diagnosing AN, because tumor size influenced lateralization in every patient, and ITD discrimination was closely correlated with the ABR findings.

Acoustic Stimulation↗

Strange hemodynamic attractor parameter with 1/R total artificial heart automatic control algorithm.

To evaluate the automatic control algorithm of the total artificial heart (TAH) as an entity, and not just as parts, a non-linear mathematical analyzing technique including chaos theory was utilized. Chronic experiments on the biventricular bypass type artificial heart implantation were performed in healthy adult goats after the natural ventricles were removed. Hemodynamic time series data were recorded under the awake standing condition with TAH 1/R and fixed driving. Time series data were recorded on a magnetic tape and analyzed on a personal computer system with an A-D converter. Using the nonlinear mathematical technique, the time series data were embedded into the phase space and the Lyapunov numerical method was carried out for the quantitative evaluation of the sensitive dependence on the initial condition of the reconstructed attractor. Calculation of the largest Lyapunov exponents suggested that the reconstructed attractor of the left pump output during TAH 1/R control was a larger dimensional strange attractor, a characteristic pattern of deterministic chaos. A total system indicating chaotic dynamics was thought to be a flexible and intelligent control system. Thus, our results suggest that 1/R TAH control may be suitable for the biventricular assist type total artificial heart.

Algorithms↗

Fluctuations of the hemodynamic derivatives during left ventricular assistance using oscillated blood flow.

To analyze the autonomic nervous system during left heart bypass with a vibrating flow pump (VFP), fluctuations in hemodynamic derivatives were evaluated by the spectral analysis method using fast fourier transform methodology. After the left pleural cavity was opened through the fourth intercostal space under general anesthesia, a VFP was implanted as the left heart bypass device in chronic animal experiments using 3 healthy adult goats. Hemodynamic parameters with and without VFP assistance were recorded on magnetic tape in awake animals and were analyzed by computer through an analog to digital convertor. Power spectral analysis was performed on a beat-to-beat basis for the evaluation of the fluctuations. During left heart bypass with the VFP, Mayer wave fluctuations were decreased significantly although respiratory waves were not changed significantly. These results suggest that sympathetic nervous system modulation was changed under the influences of the left heart bypass with VFP. By using this analysis methodology, truly physiologic ventricular assistance may be achieved.

Animals↗

Aspirin improves the enhanced erythrocyte aggregability in patients with cerebral infarction.

We examined the effect of aspirin on the enhanced erythrocyte aggregability in 19 patients with cerebral infarction during the chronic phase. Aspirin (81 mg/day) was administered for 8 weeks. The rate of erythrocyte aggregation (aggregability) was measured using the whole-blood erythrocyte aggregometer developed by us (Am. J. Physiol. 251, H1205-H1210, 1986) before, and at 4 and 8 weeks after initiation of the aspirin administration. Concomitant measurements were made of certain blood factors such as the hematocrit, albumin-globulin (A/G) ratio and fibrinogen concentration. The erythrocyte aggregation rates before, and at 4 and 8 weeks were 0.154 +/- 0.019/s, 0.144 +/- 0.020/s, and 0.143 +/- 0.020/s, respectively. The erythrocyte aggregation rates at 4 and 8 weeks were significantly (P < 0.05, Bonferroni's modified t-test) lower than that before aspirin administration. Although the hematocrit value and A/G ratio were not changed at 4 and 8 weeks after the initiation of aspirin, the concentration of fibrinogen were significantly (P < 0.05) reduced at 4 weeks. The above results suggest that aspirin can improve the enhanced erythrocyte aggregability in patients with cerebral infarction during the chronic phase.

Adult↗

[A patient with HCC successfully treated by ethanol injection therapy with etoposide].

A patient with hepatocellular carcinoma (HCC) who underwent successfully percutaneous ethanol injection therapy (PEIT) with etoposide was reported. A 72-year-old Japanese man with positive HCV-Ab developed multiple tumors of HCC. He underwent transcatheter arterial embolization (TAE) four times and PEIT three times, but the growth of tumors (particularly, S8) could not be controlled by these modalities. Then, the mixture of etoposide (20 mg), ethanol (8.5 ml) and lipiodol (1.5 ml) was injected into S6 tumors. Consistent with the normalization of serum AFP level, CT scan revealed the marked remaining lipiodol in these tumors. PEIT with etoposide is the treatment of choice in patients with HCC refractory to treatment by conventional TAE or PEIT.

Aged↗

[Application for therapeutic use of deuterium oxide (D2O) against human pancreatic cancer].

This study was designed to assess the possibility of D2O as a therapeutic agent against human pancreatic cancer. We examined the effect of D2O on growth and invasion of human pancreatic cancer cells (Panc-1, MIA PaCa-2, BxPC-3) by using MTT assay and nude mice, on which human pancreas cancer cells were transplanted. In vitro growth of the three lines was significantly inhibited by D2O in a dose dependent manner, especially at more than a 10% concentration. Growth of Panc-1, which was transplanted in nude mice, was also inhibited by continuous oral intake of 30% D2O. Furthermore, the effect of D2O on cancer invasiveness was assessed by Matrigel invasion chamber assay. BxPC-3, which is the most adherent of the three lines, significantly reduced its invasiveness in more than 30% D2O media. In addition, the present study also demonstrated the inhibition of cancer cell locomotion by D2O in phagocytokinetic analysis. In conclusion, D2O may be applied for the therapeutic use against pancreatic cancer.

Animals↗

[A surgical case of ecchordosis physaliphora].

The authors report a rare case of ecchordosis physaliphora (EP) in the prepontine region. A 51-year-old woman was admitted with a small cystic mass in the prepontine region, complaining of headache and an episode of transient double vision. Plain X-ray and lateral tomography films showed a protrusive hyperostosis at the middle clival region. The CT scan showed no abnormal densities in the retroclival region, and CT cisternography showed an isolated small round mass in the prepontine cistern. A small cystic mass with no enhancement with Gd-DTPA was revealed on MRI, mildly compressing the basilar artery and the rostral surface of the pons. The totally excised mass was pedunculated and was contiguous with the dorsal wall of the clivus via a small dural defect. The histologic diagnosis was EP, consisting of scattered physaliphorous cell nests, which were not positive for MIB-1 staining. The pedicle consisted of mature cartilaginous cells. The authors briefly reviewed the few previously reported cases of symptomatic EP and intradural chordoma, and discussed the differences between them. The histological features, especially the proliferation potential, may be pathognomonic. The histogenesis and the clinical features of symptomatic EP are also provided.

Brain Neoplasms↗