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H Sugihara

Publications and source records attributed to H Sugihara.

At least 181 records · Page 10Linked to original sources
PubMed1996

Contrast-enhanced MRI with gadodiamide injection in rat disease models.

The present study was designed to confirm the usefulness of contrast-enhanced magnetic resonance imaging (MRI) in diagnosing strokes of stroke-prone spontaneously hypertensive rats (SHRSP) and middle cerebral artery (MCA) occlusion, hepatocellular carcinoma and hydronephrosis of each experimental rat model. Male Sprague-Dawley rats (250-500 g), male SHRSP (ca. 250 g) and male F344 rats (ca. 300 g) were used for the investigation. Gadodiamide injection (Omniscan, Daiichi Pharmaceutical Co., Ltd. and Nycomed AS, Norway) was administered intravenously as the contrast agent at a dose of 0.1 mmol/kg except in hydronephrosis, where a dose of 0.05 mmol/kg was used. Magnetic resonance (MR) images were obtained with a 1.5T or a 2.0T magnetic field strength MRI unit. The signal intensity of the stroke lesions was increased after administration of gadodiamide injection in SHRSP and MCA-occluded rats. Hepatocellular carcinoma was undetectable without the use of the contrast agent, but the signal intensity of the tumor increased after administration of the gadodiamide injection, allowing the lesions to be detected. The signal intensity of the renal medulla increased in the non-ligated kidney, but not in the hydronephrotic kidney. The information given by the post-contrast images were superior to those obtained from the pre-contrast images in all the models. Contrast effects in SHRSP and MCA-occluded rats were related to differences in capillary permeability, those in rats with hepatocellular carcinoma depended on differences in vascularity, and those in hydronephrotic rats depended on blood flow and permeability.

Animals↗
PubMed1996

Contrast-enhanced MRI with gadodiamide injection in rabbit carcinoma models.

This study was designed to demonstrate the broad utility of contrast-enhanced magnetic resonance imaging (MRI) for diagnosis of carcinoma. Twenty-six New Zealand White rabbits of either sex (1.7-3.4 kg) were used for the investigation. VX2 carcinoma (squamous cell carcinoma) was implanted in either the brain, lung, ovary, bone or muscle of rabbits. Contrast agent, Gadodiamide Injection, was administered intravenously at a dose of 0.1 mmol/kg. MR images were obtained by a 1.5 T, or a 2.0 T magnetic field strength super-conductive MRI unit. The intensity of the signal for the carcinoma was increased after administration of contrast agent, and the detectability or diagnostic information of post-contrast images was superior to that of pre-contrast images in all models. In addition, no significant side effects were observed during the MRI examination. After diagnosis using MRI, morphological damage in each model was assessed by gross and histopathological examinations. In contrast-enhanced MRI, though there were variations between the models employed, contrast effects in brain and muscle carcinoma models were generally related to differences in capillary permeability, while imaging in lung, ovary and bone carcinoma models was dependent on differences in blood flow rate and the size of interstitial spaces. Overall, our results demonstrate that contrast-enhanced MRI is a useful and safe method for diagnosing tumors.

Animals↗
PubMed1996

The pathological sequence in the development of gastric cancer: I.

Although Helicobacter pylori has been designated a Group 1 carcinogen in humans, a causal role for this organism in the pathogenesis of gastric cancer has yet to be established. Histogenetically, gastric cancers have been classified into two main histological types, diffuse and intestinal, which have differing characteristics and pathogenesis. In diffuse-type cancer, minute signet ring tumours develop de novo in the neck region of glands. Gastritis caused by H. pylori infection does not contribute to the development of gastric cancer in this situation. In intestinal-type gastric cancer, the primary event is not always intestinal metaplasia, and the significance of H. pylori in this condition is not clear. There is evidence that a proportion of adenocarcinoma initially have a gastric-type phenotype, but undergo transformation to the intestinal type as the condition progresses.

Helicobacter Infections↗
PubMed1996

Antithrombotic effects of TAK-029, a novel GPIIb/IIIa antagonist, in guinea pigs: comparative studies with ticlopidine, clopidogrel, aspirin, prostaglandin E1 and argatroban.

The antithrombotic and bleeding time (BT)-prolonging effects of TAK-029, a novel glycoprotein IIb/IIIa antagonist, were characterized and compared with those of conventional antithrombotic agents in guinea pigs. TAK-029 potently inhibited the binding of fibrinogen and von Willebrand factor to purified human GPIIb/IIIa with IC50 values of 0.67 +/- 0.03 and 0.33 +/- 0.04 nM; it also inhibited human platelet aggregation induced by various aggregating agents with IC50 values of 29 to 38 nM. The in vitro antiplatelet effect of TAK-029 was potent in humans, guinea pigs and monkeys. When TAK-029 was given p.o. to guinea pigs, severe prolonging of BT (>1800 sec) was not observed with plasma concentrations of TAK-029 that inhibited ex vivo platelet aggregation by < 100%. The p.o. administration of TAK-029, ticlopidine and clopidogrel prolonged BT to the same extent, in parallel with their inhibition of ex vivo platelet aggregation. TAK-029 inhibited ex vivo platelet adhesion and thrombus formation in an arteriovenous shunt model more strongly than ticlopidine, clopidogrel and aspirin at doses causing similar prolongations of BT. In a balloon catheter-induced carotid thrombosis model, i.v. administration of TAK-029 significantly inhibited thrombus formation without prolonging BT. At doses that caused an incomplete antithrombotic effect, PGE1-alpha-cyclodextrin and argatroban produced hypotension and prolongation of BT, respectively. TAK-029 may be effective in patients suffering from arterial thrombotic diseases, which are refractory to these conventional antithrombotic agents.

Alprostadil↗
PubMed1996

Properties of Ca++ release induced by puff adder lectin, a novel lectin from the snake Bitis arietans, in sarcoplasmic reticulum.

Puff adder lectin (PAL), a novel lectin venom purified from Bitis arietans, induced Ca++ release from the heavy fraction (HSR) but not from the light fraction of skeletal muscle sarcoplasmic reticulum with EC50 congruent to 10 microM. The potency of PAL was approximately 200-fold higher than that of caffeine. The bell-shaped profile of Ca++ dependence for PAL was almost the same as that for myotoxin a (MYTX), a peptide Ca++ releaser, but was different from that for caffeine. Typical blockers of Ca++ release channels, such as Mg+2, procaine, ruthenium red and ryanodine, markedly reduced PAL-induced Ca++ release from HSR. Interestingly, PAL inhibited 125I-MYTX binding to HSR with IC50 approximately equal to 20 microM. Scatchard analysis revealed that the mode of inhibition by PAL was noncompetitive, which suggests that PAL binds to a different site from that of MYTX. PAL did not affect 3H-ryanodine binding to HSR. These results suggest that PAL binds to a different site from that of MYTX to cause Ca++ release from HSR with novel properties.

Animals↗
PubMed1996

The role of nitric oxide in dizocilpine-induced impairment of spontaneous alternation behavior in mice.

We investigated the role played by nitric oxide in the dizocilpine-induced impairment of both spontaneous alternation behavior in a Y-maze and of performance in a multiple-trial passive avoidance task in mice. Dizocilpine (0.1 mg/kg) impaired the spontaneous alternation behavior and the retention of passive avoidance without affecting acquisition in the multiple-trial passive avoidance task. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide (NO) synthase, dose-dependently impaired the spontaneous alternation behavior, but had no effect on either the acquisition or retention of passive avoidance. NG-nitro-D-arginine methylester had no effect on either task. The inhibitory effect of L-NAME on the spontaneous alternation behavior was completely reversed by the coadministration of L-arginine. Pretreatment with L-arginine ameliorated the dizocilpine-induced impairment of spontaneous alternation behavior, but not the impairment of the retention of passive avoidance. S-Nitroso-N-acetylpenicillamine, a generator of NO, completely inhibited the dizocilpine-induced impairment of spontaneous alternation behavior. Finally, the impairment of spontaneous alternation behavior caused by dizocilpine was significantly diminished by pretreatment with dibutyryl cyclic GMP. These results suggest that, although N-methyl-D-aspartate receptors play a critical role in both spatial working memory and long-term memory processes assessed by spontaneous alternation behavior and the passive avoidance, respectively, different neuronal mechanisms may be involved in these two processes. Further, it is suggested that the NO/cyclic GMP system may play a role in spatial working memory.

Animals↗
PubMed1996

[The serial change of the 123I-BMIPP SPECT in patients with hypertrophic cardiomyopathy].

We studied the serial change of 123I-BMIPP SPECT in the process of hypertrophic cardiomyopathy (HCM). In 16 patients with HCM, the imaging data were acquired 15 minutes after injection of 111 MBq 123I-BMIPP. The SPECT image was divided into 17 segments and the severity of the defect in each segment was scored visually using defect score, a 4-point grading system (score 0 = normal, score 1 = mildly decreased uptake, score 2 = moderately decreased uptake, score 3 = severely decreased uptake or defect). Each patient underwent this examination twice with interval of 25 +/- 14 months. In the first examination, we observed reduced uptake in 14 cases (88%), and often found it in septal portion of anterior or posterior wall. In the second examination, compared with the first study, total defect score (TDS: the summation of defect score of 17 segments) had increased in 7 cases (44%) of 16 cases, decreased in only 1 case (6%), and unchanged in 8 cases (50%). The regional defect score often increased in septal portion of anterior and posterior walls, and the high score area widespread toward the septum. There was no difference between TDS unchanged group and TDS worsened group in the point of background (age, family history of HCM), the interval of the two studies, and the findings of echocardiography (Dd, Ds, %F). In TDS worsened group (n = 7), clinically only 1 case became progressed stage. In others there were no progression in each clinical, echocardiographic, or 201Tl scintigraphic findings. This study revealed that myocardial fatty acid metabolic disorder often progresses during short interval in patients with HCM. In conclusion, the serial examination of 123I-BMIPP SPECT may contribute to an estimation of the stage or the prognosis in HCM.

Adult↗
PubMed1995

Effects of hyper- and hypoglycemia on blood growth hormone level in free-feeding rats with anterolateral deafferentation of the medial basal hypothalamus.

In rats with anterolateral deafferentation of the medial basal hypothalamus, the growth hormone (GH) level in the blood showed irregular and small fluctuations instead of the usual high bursts and low trough level, and the baseline GH level was higher than that in sham-operated rats. Continuous infusion of a glucose solution to operated rats increased the baseline level, GH pulse and pulse amplitude. I.v. bolus injection of the glucose solution resulted in a significant but transient increase in GH level. Insulin-induced hypoglycemia decreased the blood GH level in operated rats more effectively than in sham-operated ones and that was prevented by simultaneous infusion of glucose. Since SS influence on GH secretion had been largely eliminated in rats with anterolateral deafferentation of the medial basal hypothalamus, it is highly unlikely that the effects of hyperglycemia or hypoglycemia on GH secretion were the consequence of altered SS secretion.

Animals↗
PubMed1995

Primary structure of a coagulant enzyme, bilineobin, from Agkistrodon bilineatus venom.

The amino acid sequence and disulfide bridge location of the coagulant enzyme, named bilineobin, isolated from the venom of Agkistrodon bilineatus was determined by Edman sequencing of the peptides derived from digests with cyanogen bromide, clostripain, Staphylococcus aureus V8 protease, trypsin, and chymotrypsin. This enzyme has a molecular weight of 57,000 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; however, bilineobin consists of 235 amino acids and has a calculated molecular weight of 26,481. The enzyme contains fucose, GlcNAc, galactose, mannose and NeuAc and six N-linked glycosylation consensus sites. The carboxyterminal amino acid, proline, was determined using carboxypeptidase Y. The six disulfide bonds of bilineobin link Cys78 to Cys234, Cys120 to Cys188, Cys178 to Cys203, Cys7 to Cys141, Cys152 to Cys167, and Cys28 to Cys44. The amino acid sequence similarity to flavoxobin (T.C. Shieh et al., 1988, J. Biochem (Tokyo) 103, 596-605) and batroxobin (N. Itoh et al., 1987, J. Biol. Chem. 262, 3132-3135) was 67%. The deglycosylated enzyme more rapidly generated fibrinopeptide A than native bilineobin.

Agkistrodon↗
PubMed1995

Central glucoprivation evoked by administration of 2-deoxy-D-glucose induces expression of the c-fos gene in a subpopulation of neuropeptide Y neurons in the rat hypothalamus.

Central glucoprivation evoked by the intracerebroventricular administration of 2-deoxy-D-glucose (2DG) induces eating and suppresses growth hormone (GH) secretion in rats. To elucidate the hypothalamic mechanism of these phenomena, the induction of c-fos gene expression was examined by in situ hybridization using rats with centrally administered 2DG. Autoradiography on X-ray film showed that c-fos gene expression was transiently induced in discrete hypothalamic regions; namely the paraventricular nucleus, arcuate nucleus (ARC), the surrounding regions of the third ventricle dorsal to the ARC, and the periventricular nucleus (PeV). The time course of the expression was different in these nuclei. Double-label in situ hybridization for c-fos mRNA and neuropeptide Y (NPY) or somatostatin mRNAs revealed that 20% of the NPY neurons in the ARC expressed the c-fos gene, while a small population of somatostatin neurons (6.1% in the ARC and 2.6% in the PeV) expressed the c-fos gene following 2DG administration. Since NPY is an orexigenic neuropeptide and has an inhibitory effect on GH secretion, the data suggest that the activation of a subpopulation of NPY neurons in the ARC contributes, in part, to the increased food intake and suppression of GH secretion after central glucoprivation evoked by 2DG.

Animals↗
PubMed1995

In situ hybridization: a new technique to determine the origin of fibroblasts in cryopreserved aortic homograft valve explants.

Tissue degeneration reduces the durability of cryopreserved homografts. Earlier studies indicated that the presence of fibroblasts in homograft leaflets may contribute to increased valve longevity. These fibroblasts may be of recipient origin or represent surviving donor cells. We developed a method, based on in situ hybridization, to determine the origin of fibroblasts in homograft explants. In young pigs we performed aortic valve replacement with a cryopreserved porcine aortic homograft. A male homograft was implanted in a female pig, whereas two male recipients received a female homograft. After 3 to 4 months the homografts were explanted. Frozen sections were made and alternately examined with hematoxylin-eosin staining and in situ hybridization. With a biotinylated porcine Y chromosome-specific deoxyribonucleic acid probe, male fibroblasts could be clearly distinguished from female fibroblasts. In all leaflets we observed both donor and recipient fibroblasts. The distribution of these populations was marked in schematic drawings. Recipient fibroblasts mostly spread onto the leaflet surface but also penetrated the leaflet tissue. Remaining donor fibroblasts did not show morphologic signs of decreased viability on hematoxylin-eosin staining. In situ hybridization may become a useful technique in homograft research. In this porcine model, the fibroblasts in the aortic homograft explants were of both donor and recipient origin.

Animals↗
PubMed1995

Caloric intake stimulates growth hormone secretion in food-deprived rats with anterolateral deafferentation of the medial basal hypothalamus or administered antiserum to somatostatin.

In rats, food deprivation inhibits episodic growth hormone (GH) secretion. On the basis of previous studies, we hypothesized that during a recovery from prolonged fasting, caloric intake stimulates the release of GH-releasing factor (GRF) and this process does not depend on the specific macronutrients in the meal, while protein in the meal acts to restore characteristic ultradian rhythmicity of GH secretion. To test this hypothesis, the effect of caloric intake on GH secretion was examined in fasted adult male Wistar rats devoid of somatostatin (SS) influence on GH secretion either by anterolateral deafferentation (ALC) of the medial basal hypothalamus (MBH) or administration of anti-SS goat serum (ASS). Rats were provided with an indwelling right atrial cannula and were deprived of food for 72 h. ALC was performed 2 weeks prior to the study. ASS was given i.v. 8 h and 7 h prior to refeeding, respectively. Serial blood specimens were collected every 10 min. In rats with ALC (ALC rats) or rats given ASS (ASS rats), the blood GH level revealed irregularly occurring small fluctuations, instead of the usual high bursts and low trough level. The baseline GH level and the mean GH level of fasted ALC rats or fasted ASS rats were significantly lower than those of fed ALC rats or fed ASS rats. Feeding the isocaloric mixed meal, the protein meal or the protein-deficient meal increased the GH pulse frequency, the pulse amplitude, the baseline GH level and the mean GH level in 72-h fasted ALC rats. These changes in GH secretory pattern persisted during the period of observation and were independent of the type of meal ingested. Following feeding the mixed meal, similar changes in the GH secretory pattern demonstrated in 72-h fasted ALC rats were also observed in 72-h fasted ASS rats, suggesting that the stimulation of GH secretion following caloric intake is not limited to ALC rats. Since the influence of SS on GH secretion has been largely eliminated in ALC or ASS rats, it is highly unlikely that the augmentation of GH secretion following feeding after prolonged food deprivation was the consequence of inhibition of SS secretion. Although GRF measurement was not performed, it is conceivable that the signal of caloric intake is conveyed to the MBH and acts to stimulate GRF release.

Animals↗
PubMed1995

Role of nitric oxide in learning and memory and in monoamine metabolism in the rat brain.

1. We investigated the effects of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, on the performance of rats in a radial arm maze and in habituation tasks, and on monoamine metabolism in the brain. 2. Daily administration of L-NAME (10-60 mg kg-1) resulted in a dose-dependent impairment of performance during the acquisition of the radial arm maze task, while it failed to affect performance in those rats that had previously acquired the task. 3. The rate of decrease in locomotor activity in the habituation task in the L-NAME-treated rats was significantly less than that in control rats. 4. NG-nitro-D-arginine methyl ester (D-NAME, a less active inhibitor of NO synthase) showed no effects in the above behavioural tasks. 5. NO synthase activity was significantly decreased in both the L-NAME and D-NAME-treated rats, with the magnitude of inhibition being greater in the L-NAME-treated animals. 6. The content of 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and the 5-HIAA/5-hydroxytryptamine ratio in the hippocampus and cortex were significantly decreased in the L-NAME (60 mg kg-1)-treated rats compared with these values in the controls. 7. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) content was significantly increased in the L-NAME (60 mg kg-1)-treated rats compared with the values in the controls, while the DOPAC/dopamine ratio was not changed. 8. These results suggest that: (i) NO may play an important role in performance during the acquisition,but not retention, of the radial arm maze task, and (ii) that endogenous NO may be involved in the regulation of monoamine metabolism.

Animals↗
PubMed1995

Expression of the O9 polysaccharide of Escherichia coli: sequencing of the E. coli O9 rfb gene cluster, characterization of mannosyl transferases, and evidence for an ATP-binding cassette transport system.

The rfb gene cluster of Escherichia coli O9 directs the synthesis of the O9-specific polysaccharide which has the structure -->2-alpha-Man-(1-->2)-alpha-Man-(1-->2)-alpha-Man-(1-->3)-alpha- Man-(1-->. The E. coli O9 rfb cluster has been sequenced, and six genes, in addition to the previously described rfbK and rfbM, were identified. They correspond to six open reading frames (ORFs) encoding polypeptides of 261, 431, 708, 815, 381, and 274 amino acids. They are all transcribed in the counter direction to those of the his operon. No gene was found between rfb and his. A higher G+C content indicated that E. coli O9 rfb evolved independently of the rfb clusters from other E. coli strains and from Shigella and Salmonella spp. Deletion mutagenesis, in combination with analysis of the in vitro synthesis of the O9 mannan in membranes isolated from the mutants, showed that three genes (termed mtfA, -B, and -C, encoding polypeptides of 815, 381, and 274 amino acids, respectively) directed alpha-mannosyl transferases. MtfC (from ORF274), the first mannosyl transferase, transfers a mannose to the endogenous acceptor. It critically depended on a functional rfe gene (which directs the synthesis of the endogenous acceptor) and initiates the growth of the polysaccharide chain. MtfB (from ORF381) then transfers two mannoses into the 3 position of the previous mannose, and MtfA (from ORF815) transfers three mannoses into the 2 position. Further chain growth needs only the two transferases MtfA and MtfB. Thus, there are fewer transferases needed than the number of sugars in the repeating unit. Analysis of the predicted amino acid sequence of the ORF261 and ORF431 proteins indicated that they function as components of an ATP-binding cassette transport system. A possible correlation between the mechanism of polymerization and mode of membrane translocation of the products is discussed.

ATP-Binding Cassette Transporters↗
PubMed1995

Effects of various types of extracellular matrices on adhesion, proliferation, differentiation, and c-fos protein expression of porcine thyroid follicle cells.

Thyroid follicles in vivo are embedded in extracellular matrix (ECM). The composing epithelial cells are in close contact with ECM at the basal side. To examine cell-to-ECM interactions, we studied adhesion, proliferation and differentiation of porcine follicle cells monolayer-cultured on type I and IV collagen, fibronectin or laminin. At 3 h in culture, laminin had the lowest rate of cell adhesion. In proliferation, type IV collagen induced the highest level of nuclear bromodeoxyuridine intake. In a functional differentiation, laminin had about 3 times as much triiodothyronine production as the other ECM molecules. In confluent culture cells, we also examined an expression of c-fos protein, a transcription factor that plays crucial roles in signal transduction. Immunocytochemistry detected the protein mainly in the nuclei. Western blot showed that laminin induced the highest level of its expression. Thyrotropin (TSH, 10 mU/ml) did not affect adhesion of the cells on any of the substrata or proliferation of the cells on fibronectin; nor did TSH affect c-fos protein expression of the cells on the substrata except for fibronectin. Our results suggest that type IV collagen and laminin, major components of basement membrane, play positive roles in proliferation and differentiation of follicle cells, respectively, while laminin has no positive effect on adhesion of the cells at early culture; that the cells express c-fos protein even in contact inhibition of growth and its expression is regulated in part by ECM; and that ECM controls some behaviors of the cells in a TSH-dependent or TSH-independent manner.

Animals↗
PubMed1995

A rare case of primary pulmonary choriocarcinoma in a male: immunohistochemical detection for human chorionic gonadotropin, epidermal growth factor (EGF) and EGF-receptor.

a rare case of primary choriocarcinoma of the lung in a male is described with immunohistochemistry for human chorionic gonadotropin (hCG), epidermal growth factor (EGF) and EGF-receptor. The extragonadal trophoblastic origin of this pulmonary carcinoma was definitely confirmed by an autopsy examination, and hCG-production and hCG-positive staining of the tumor cells. Furthermore, the tumor cells clearly expressed EGF and its receptor which play an important role in the proliferation and differentiation of normal and neoplastic trophoblasts of the uterus. Our present case suggests that EGF may act in an autocrine manner in the tumor cells of primary pulmonary choriocarcinoma.

Aged↗