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Biomedical subjects

H Satake

Publications and source records attributed to H Satake.

At least 37 records · Page 2Linked to original sources

Characterization of a cDNA encoding a precursor polypeptide of a D-amino acid-containing peptide, achatin-I and localized expression of the achatin-I and fulicin genes.

Achatin-I and fulicin, isolated from the ganglia and atria of the giant land snail Achatina fulica, are a tetrapeptide and pentapeptide containing a d-Phe and d-Asn at position 2, respectively. We succeeded in cloning a cDNA encoding a precursor of achatin-I from the Achatina ganglia, revealing that the d-Phe present in achatin-I is coded by a common l-Phe codon, TTT or TTC. The deduced polypeptide was found to comprise seven repeats of the achatin sequence GFAD and one analog GFGD flanked on both sides by the typical endoproteolytic site KR. Northern blot analysis of transcripts and Southern blot analysis of reverse transcription (RT)-PCR products demonstrated that achatin-I mRNA was localized in the subesophageal ganglia, whereas expression of fulicin mRNA was detected in the atrium as well as in the subesophageal ganglia. Furthermore, localization of the achatin gene transcript in the right and left pedal ganglia compartments was shown by in situ hybridization on sections of subesophageal ganglia, whereas the fulicin transcript was observed in the right and left parietal ganglia. These data suggested that achatin-I plays an essential role in the regulation of the heart as a neurotransmitter or neurohormone through production in the pedal ganglia and transport to the atrium, whereas fulicin serves not only as a neurotransmitter or neurohormone but also as a novel atrial hormone.

Amino Acid Sequence↗

Effects of hyper +Gz acceleration on brainstem and auditory cortical evoked potentials and cerebral blood flow in anesthetized rats.

Hypergravity acceleration along the long axis of the body (Gz) causes severe cardiovascular dysfunctions. Many studies have been conducted along this line. However, most previous studies used rather a short duration of hyper-Gz application, up to 30 sec, because application of large hyper-Gz brings animals into death. In order to elucidate effects of long duration of Gz application, we made experiments with Gz load for as long as 1000 sec. Cardiovascular dysfunctions and reduction of arterial blood pressure were usually accompanied by reduction of cerebral blood flow, leading subjects into loss of consciousness and into death. Recently, we studied the effects of +Gz load on evoked potentials. The present experiments shows effects of +Gz on brainstem auditory response and auditory evoked potentials.

Acceleration↗

Membrane-buffer partition coefficients of a local anesthetic tetracaine monitored by an anesthetic sensor; effects of temperature and pH.

Binding of a local anesthetic tetracaine (TC) to dimyristoylphosphatidylcholine (DMPC) bilayer membrane was studied by the potentiomerty with an ion-selective electrode sensitive to TC cation. DMPC membrane-buffer partition coefficient (K(app)) was determined in mole fraction unit as a function of pH for the lamellar gel (at 12 degrees C), ripple gel (at 20 degrees C), and liquid crystal (at 30 degrees C) phases. The partition coefficients of charged (K+) and uncharged TC (K0) into the DMPC membranes were estimated from the pH-dependence of K(app). The three states of DMPC membranes were more receptive to the uncharged TC than the charged species.

Algorithms↗

Preoperative staging of thyroid papillary carcinoma with ultrasonography.

OBJECTIVE: To evaluate the usefulness of ultrasonography including Doppler flow imaging for the preoperative staging of thyroid papillary carcinoma. MATERIALS AND METHODS: In 77 patients with thyroid papillary carcinoma who underwent total thyroidectomy, the accuracy of ultrasonography in preoperative clinical staging was assessed with use of pathologic examination on the basis of TNM classification by the International Union Against Cancer (UICC). RESULTS: In 63 (81.8%) cases, T categories were estimated accurately. The sensitivity in depicting tumor extension into the prethyroidal muscle and/or the sternocleidomastoid muscle was 77.8%, whereas the sensitivity for invasion into the trachea and the esophagus was 42.9 and 28.6%, respectively. In 37 (48.1%) cases, N categories were underestimated, and the sensitivity in the detection of regional lymph node metastasis was 36.7%. Doppler flow imaging was performed in 36 patients, and no correlation was found between flow patterns and the presence of local invasion or regional lymph node metastasis. CONCLUSION: Ultrasonography was useful for preoperative investigation of thyroid papillary carcinoma, but several limitations existed, especially in evaluating extracapsular invasion to deep locations and regional lymph node metastasis.

Adult↗

Interobserver agreement in sonographic diagnosis of breast tumors.

OBJECTIVE: To evaluate interobserver agreement in the interpretation of breast ultrasonography. METHODS: 55 breast masses (30 benign, 24 malignant) were interpreted by seven radiologists using a CRT viewing station. US criteria for differentiating between benign and malignant lesions included shape, border, boundary echoes, internal echoes, posterior echoes, and bilateral shadows. Each criterion and the observers' final impression was scored using the 5-point rating scales. For analyzing interobserver agreement, the kappa (kappa) values were employed. RESULTS: The kappa values of shape and posterior echoes were significantly higher than those of the other four criteria (P<0.05). Agreement was intermediate in border and internal echoes, and was low in boundary echoes and bilateral shadows. Agreement in the senior group (four observers) was relatively higher than that in the junior group (three observers) for all criteria but for internal echoes. Easily-diagnosed cases showed significantly higher kappa values compared with more ambiguous cases (P<0.05). CONCLUSION: Interobserver agreement in shape and posterior echoes was significantly higher than those of the other four criteria. Agreement was significantly dependent on case difficulty.

Breast Diseases↗

Pranidipine, a new 1,4-dihydropyridine calcium channel blocker, enhances cyclic GMP-independent nitric oxide-induced relaxation of the rat aorta.

Pranidipine, a new calcium channel blocker, prolonged endothelium-dependent relaxation induced by acetylcholine in an aortic ring preparation, contracted with prostaglandin F2alpha. This action was not shared by amlodipine. The effect was not modified by indomethacin, suggesting that the action of pranidipine does not involve prostanoid metabolism. N(G)-nitro-L-arginine completely prevented the action of Pranidipine. The drug affected neither nitric oxide (NO) synthase activity nor the level of cyclic GMP in the vessel. Pranidipine did not affect the sensitivity of the contractile proteins to calcium. Pranidipine also did not alter cyclic GMP-induced relaxation in alpha-toxin-skinned vascular preparations. Pranidipine also prolonged glyceryl trinitrate-induced relaxation in the endothelium denuded rat aorta. Furthermore, pranidipine enhanced relaxation of the aorta induced by glyceryl trinitrate even in the presence of methylene blue, a guanylyl cyclase inhibitor. This action was not modified by iberiotoxin or by charybdotoxin, two inhibitors of the calcium-activated potassium channel. The results strongly suggest that pranidipine enhances cyclic GMP-independent NO-induced relaxation of smooth muscle by a mechanism other than through NO-induced hyperpolarization. These effects were in direct contrast to amlodipine, another new 1,4-dihydropyridine calcium antagonist.

Amlodipine↗

Preclinical antitumor efficacy of S-1: a new oral formulation of 5-fluorouracil on human tumor xenografts.

S-1 is a new oral formulation of 5-fluorouracil (5-FU) consisted of 1M tegafur, 0.4M 5-chloro-2,4-dihydroxypyridine that inhibits a degradation of 5-FU, and 1M potassium oxonate that regulates the phosphorylation of 5-FU in the gastrointestinal tract, and has shown excellent antitumor efficacy against various murine tumors in rodents, compared to the oral tegafur-based antitumor drug, UFT (1M tegafur plus 4M uracil), which is used clinically in Japan. To assess the possibility of clinically using S-1, we investigated the antitumor effect of S-1 on various human solid tumor xenografts in athymic rats and mice. In the nude rat system, S-1 was significantly effective against all 12 tumor xenografts tested when its minimum toxic dose (15 mg/kg) was administered for 14 days. Three tumors, stomach (H-81), colon (KM12C) and breast (H-31) markedly regressed in response to treatment with S-1 but not with UFT. The antitumor potency of S-1 was weak against human tumors xenografted into nude mice and likely similar to that of UFT. The reason of the discrepancy in the efficacy of S-1 between rats and mice was found to be that the 5-FU levels in the blood and tumor tissue of rats after oral administration of S-1 persisted much longer than in mice, and this prolonged maintenance of plasma 5-FU levels was significantly related to the potent antitumor activity of S-1. In conclusion, the results of this study suggested that based on its biological and pharmacokinetic characteristics, oral S-1 should be active against various human cancers.

Administration, Oral↗

Effects of hyper +Gz acceleration on cardiovascular function, visual evoked potentials and cerebral blood flow in anesthetized rats.

Sustained hyper-gravity acceleration, particularly along the long axis of the body of animals or man (Gz), produces significant mal-effects on subjects, and hence it has been well studied, The most common syndromes of Gz application were cardio-vascular de-conditioning, and black-out, red-out, and loss of consciousness, which finally lead subjects into death. However, in most previous studies, the duration of applied Gz was rather short. In the present experiments, we can use longer duration of 1000 seconds. In addition, recent technological innovation make it possible to record directly local cerebral blood flow at a target cortical area with a Laser Doppler flow meter. We used this innovated method to measure local cerebral blood flow of rats in relation to visual evoked potentials (VEPs) under hyper-Gz acceleration. Also we recorded cardio-vascular parameters like heart rate from ECG, systolic and diastolic blood pressure and correlated them with cerebral blood flow and VEPs.

Acceleration↗

[MR-cholangiopancreatography using three-dimensional Fourier transfer fast asymmetric spin-echo method (3DFT-FASE)--clinical evaluation].

MR-cholangiopancreatography (MRCP) is a new and non-invasive method. With the three-dimensional Fourier transform fast asymmetric spin-echo (3DFT-FASE) method that allows data collection as volume and three-dimensional expression, a higher spatial resolution can be obtained in the direction of both slab thickness and in-plane. In this method, analysis by multi planar reconstruction (MPR) and observation from various angle by maximum intensity projection (MIP) are available. Although further studies are required to shorten the imaging time to stop breathing only once, to use the respiratory gating or navigator echo, clinically useful diagnosis are possible utilizing by the advantages of the 3DFT method.

Biliary Tract↗

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats.

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Adenocarcinoma↗

An artificial CuII complex with intriguing oxygen radical-quenching profile. X-ray structure, cytochrome c assay, and ESR study.

A novel artificial peptide named HPH-Pep, comprising a pyridine and two histidine units, was synthesized. The HPH-Pep-CuII complex had unique pentacoordinated structure as shown by X-ray crystallography and exhibited superoxide-scavenging activity as indicated by ESR spectroscopy. The superoxide-quenching profile of HPH-Pep-CuII was studied in detail by cytochrome c assay and ESR spin trapping and it was found that (1) HPH-Pep-CuII did not scavenge hydrogen peroxide or hydroxyl radical and hence the scavenging activity was specific to superoxide, and (2) HPH-Pep-CuII did not generate hydrogen peroxide upon scavenging superoxide.

Copper↗

[Inhibition of prostate cancer growth in nude mice by hormone and chemotherapy].

The combined effect of hormone and cytotoxic therapy on the growth of prostate cancer PC-3 in nude mice was investigated. PC-3 cell was derived from the bone metastasis of a hormone-refractory prostate cancer. Each group consisted of seven animals. After the inoculation of cancer cells, diethylstilbestrol (DES: 20 mg/kg) and futraful with uracil (UFT: 20 mg/kg) were administered for 25 days. DES and UFT synergically inhibited the growth. DES had no effect as a single agent on the growth of a hormone-independent cell line (KM20C) derived from human colon cancer. It also had no additive effect when given with UFT.

Animals↗

[Helical CT for lung-cancer screening: third report: fundamental study for ultralow-dose CT by application of small tube current and filter].

In order to develop ultra-low-dose helical CT for lung cancer screening, the effect of reduction of the tube current to 20mA and application of a 10mm thick aluminium filter upon radiation dose and image quality was evaluated with a phantom. Exposure dose at the center of a gantry and absorbed dose at the center of an acrylic phantom at 20mA with the filter were 15% and 29% of the dose at 50mA without the filter, respectively. For reduction of absorbed dose, reduction of the tube current was more useful than application of the filter. Image noise at 20mA with the filter was double that at 50mA without the filter. Neither reduction of the tube current nor application of the filter changed full width at half maximum on section sensitivity of the Z-axis. Although reduction of the tube current did not affect the difference in CT values between an acrylic sphere and styroform, application of the filter caused a reduction of 4.5% in the difference in CT values. Neither reduction of the tube current nor application of the filter affected the contrast resolution of the high-contrast phantom; however, that of the low-contrast phantom deteriorated. Although improvement of the filter and evaluation of clinical images are necessary, reduction of the tube current to 20mA and application of the aluminium filter appear to be a promising method for ultra-low-dose helical CT of the lung.

Filtration↗

[Helical CT for lung-cancer screening: fourth report. Detectability of pulmonary lesions].

The detectability of various abnormal findings in helical screening CT(HSCT) with low-dose and single-breath-hold scanning of the lung was examined using conventional CT as a gold standard. In 75 patients, HSCT was obtained with scanning parameters of 120kVp, 50 mA, 10 mm-collimation. 20 mm/second and 1 sec/rotation. Conventional CT was obtained with 150 mA and 10 mm-slice contiguous scanning HSCT depicted 141 of 159 focal lesions in nodules and masses (65 of 69 lesions more than 5mm in size), 44 of 47 in infiltrative lesions, 11 of 11 in reticular lesions and 23 of 39 in bullae and blebs. There were only 3 false positive lesions in nodule and mass. Sensitivity, specificity and accuracy of HSCT for diffuse lesions were 100% (11/11), 95% (61/64) and 96% (72/75) for fibrotic change and 75% (9/12), 100% (63/63) and 96% (72/75) for emphysematous change, respectively. Since the detectability of HSCT was good for abnormal findings, showing increased attenuation in comparison with the lung parenchyma, it was considered to be a promising method for lung-cancer screening.

Adult↗

Cupric ion blocks NF kappa B activation through inhibiting the signal-induced phosphorylation of I kappa B alpha.

A transcription factor NF kappa B, which regulates expression of various cellular genes involved in immune responses and viral genes including HIV, is sequestered in the cytoplasm as a complex with an inhibitory protein I kappa B. Various extracellular signals induce phosphorylation and rapid degradation of I kappa B alpha to release NF kappa B. Cu2+ was found to inhibit the activation of NF kappa B induced by TNF-alpha, TPA, or H2O2. Deoxycholate treatment of the cytoplasmic extract prepared from cells stimulated by TNF-alpha in the presence of Cu2+ resulted in the release of NF kappa B from I kappa B alpha, indicating that Cu2+ interferes with the dissociation of the NF kappa B-I kappa B complex. Neither phosphorylation nor degradation of I kappa B alpha was observed upon TNF-alpha stimulation in the presence of Cu2+. These results indicate that Cu2+ inhibits the release of NF kappa B by blockade of a signal leading to the phosphorylation of I kappa B alpha.

Animals↗

Histopathological evaluation of gastric mucosal environments in peptic ulcer using the endoscopic 5-point gastric biopsy method.

Although a strong association has been established between chronic Helicobacter pylori infection and peptic ulcers, the role of H. pylori is not necessarily causative because there are many patients infected with H. pylori who do not develop peptic ulcer. Therefore, we studied the relationship between the gastric mucosal environment and the development of peptic ulcers. We examined 165 endoscopic biopsy specimens from the gastric mucosa of 33 patients with peptic ulcers using the 5-point gastric biopsy method. The follow-up biopsies done within 3 weeks were well correlated with the first biopsy samples. We also reviewed the clinicohistopathological findings of 2250 endoscopic biopsy specimens from 450 patients with active gastric and/or duodenal ulcers. Over 90% of the patients with duodenal ulcer, with or without gastric ulcer, had no fundic gland atrophy, and a high incidence of intestinal metaplasia and pyloric mucosal atrophy was found in the patients with gastric ulcer. These findings suggest that patients with concomitant active gastric and duodenal ulcers exhibit severe atrophic changes in the antral mucosa but not in the fundic mucosa.

Adult↗

Cardiovascular responses to KC-135 hyper-gravity.

The present study was designed with two intentions; Are the effects of angular velocity detectable in the cardiovascular responses during the hyper-G? Another is object to examine how the otolith signal could modify the cardiovascular responses provoked by the exposure to the hyper-G. NASA/KC-135 hyper-gravity flight was used to generate high gravito-inertial forces to exclude a possible effect of angular velocity. Six healthy subjects was indicated to make dorsal flexion of the neck to reduce the otolith input. An exposure to +l.8Gz stress resulted in a remarkable increase of systolic and diastolic blood pressure, thereby pulse pressure became a little bit narrower. R-R interval revealed a tachycardia during the hyper-G except one subject. The present experiment bore the similar cardiovascular responses as those observed in the previous studies with a short rotating radius, suggesting that almost no effect of angular velocity acts on their responses. A weaker otolith input could possibly work on them. However a systematical observation can not recognize among the subjects for the vestibular effect on the cardiovascular responses. This fact of vestibular qualification leads us to speculate that it would depend on the subjects or other factors.

Adult↗