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Biomedical subjects

H Ito

Publications and source records attributed to H Ito.

At least 577 records · Page 32Linked to original sources
PubMed1999

Brain temperature modifies glutamate neurotoxicity in vivo.

The purpose of this study was to examine the effects of mild hypothermia and hyperthermia on glutamate excitotoxicity. Glutamate-induced cortical lesions were produced in hypothermic (32 degrees C), normothermic (37 degrees C), and hyperthermic (40 degrees C) rats by perfusion of a 0.5 M glutamate solution via a microdialysis probe. The volume of the lesion 7 days after glutamate perfusion was quantified histologically by image analysis. This histological assessment was performed in two experiments; in one, each of the target temperatures was induced before glutamate perfusion, and in the other, each of the target temperatures was induced after stopping the glutamate perfusion. We also examined the effect of temperature on the diffusion of exogenously delivered material in the extracellular space using autoradiography of the perfused glutamate solution containing 14C-labeled sucrose. In the two experiments in which each of the target temperatures was induced before or after glutamate perfusion, the volume of damage was reduced by mild hypothermia and enlarged by mild hyperthermia. The volume of 14C diffusion also increased as brain temperature increased. These results provide evidence that small variations of brain temperature modify glutamate excitotoxicity. The results also suggest that the change in glutamate diffusion in the extracellular space is one mechanism by which mild hypothermia and hyperthermia exert their protective and harmful effects respectively.

Analysis of Variance↗
PubMed1999

HLA-DPB1*0501-associated opticospinal multiple sclerosis: clinical, neuroimaging and immunogenetic studies.

In order to clarify the relationship between the clinical phenotype and the human leucocyte antigen (HLA) in multiple sclerosis in Asians, 93 Japanese patients with clinically definite multiple sclerosis underwent clinical MRI and HLA-DPB1 gene typing studies. According to a neurological examination, 29 patients were classified as opticospinal multiple sclerosis, 17 as spinal multiple sclerosis and 47 as Western type multiple sclerosis showing the involvement of multiple sites in the CNS including either the cerebrum, cerebellum or brainstem. The opticospinal multiple sclerosis showed a significantly higher age of onset, higher expanded disability status scale scores and higher CSF cell counts and protein content than the Western type multiple sclerosis. On brain and spinal cord MRI, the opticospinal multiple sclerosis showed a significantly lower number of brain lesions, but a higher frequency of gadolinium-enhancement of the optic nerve and a higher frequency of spinal cord atrophy than in Western type multiple sclerosis. The frequency of the HLA-DPB1*0501 allele was found to be significantly greater in opticospinal multiple sclerosis (93%) than in healthy controls (63%, corrected P value = 0.0091 and relative risk = 7.9), but not in Western type multiple sclerosis (66%) or spinal multiple sclerosis (82%). The marked differences in the clinical and MRI findings as well as in the immunogenetic backgrounds between the opticospinal multiple sclerosis and Western-type multiple sclerosis together suggest that HLA-DPB1*0501-associated opticospinal multiple sclerosis is a distinct subtype of multiple sclerosis.

Adult↗
PubMed1999

Inhibition of hepatocellular carcinoma by glycyrrhizin in diethylnitrosamine-treated mice.

Glycyrrhizin (GL) is widely used in Japan as a therapeutic agent for chronic active liver diseases. However, its action on hepatocarcinogenesis remains to be elucidated. To clarify its effect, mice treated with diethylnitrosamine (NDEA) with or without GL were analyzed. Five-week-old male BALB/c mice were divided into two groups, GL (n=50) and C (n=47). Mice in the GL group intramuscularly received 2 mg of GL 3 days a week, and mice in the C group received the same volume of saline in the same way. After 2 weeks, the mice were treated with an i.p. injection of 75 mg/kg body wt of NDEA weekly for 3 weeks and 100 mg/kg body wt of NDEA weekly for the following 3 weeks. Thirty additional mice that did not receive NDEA treatment were divided into two groups, GC (n=15) and SC (n=15). They received GL or saline, respectively. Mice in the 4 groups were killed every 5 weeks after the last injection of NDEA from 7 weeks to 32 weeks. Liver function tests such as AST and albumin were significantly improved in the GL group compared with the C group (P < 0.05, each). Although liver nodules appeared in the C group at 22 weeks, they were not observed until 32 weeks in the GL group. At 32 weeks, the mean number of liver tumors, composed of adenoma and hepatocellular carcinoma (HCC), in the GL group was 0.71, which was significantly decreased compared with 1.64 of the C group (P < 0.05). The mean number of HCC in the GL group was 0.29/liver, which was lower than 0.82/liver in the C group (P < 0.05). The incidence rate of HCC at 32 weeks was 64% in the C group and 21% in the GL group (P < 0.05, C versus GL group). Our results suggest that GL treatment inhibits the occurrence of HCC.

Adenoma↗
PubMed1999

Purification and further characterization of enteropeptidase from porcine duodenum.

Enteropeptidase [EC 3.4.21.9] is a membrane-bound serine endopeptidase present in the duodenum that converts trypsinogen to trypsin. We previously cloned the cDNA of the porcine enzyme and deduced its entire amino acid sequence [M. Matsushima et al. (1994) J. Biol. Chem. 269, 19976-19982]. In the present study, we purified the porcine enzyme approximately 2,200-fold in a 12% yield from a duodenal mucosal extract to apparent homogeneity by an improved procedure comprising four steps of chromatography including benzamidine-Sepharose affinity chromatography. Lectin blotting analysis suggested that the enzyme is glycosylated mainly with N-linked carbohydrate chains of the tri- and/or tetraantennary complex type. The H and L chains of the enzyme were separated into two major bands upon SDS-PAGE under reducing conditions, suggesting that the enzyme mainly comprises two isoforms, a higher molecular weight form and a lower molecular weight form. The enzyme was also separated by lectin affinity chromatography into two major fractions, named isoforms I and II, which corresponded to the higher and lower molecular weight forms, respectively. These two isoforms appeared to be different only in the carbohydrate moiety, having essentially the same enzymatic properties. The enzyme was optimally active at pH 8.0 toward Gly-Asp-Asp-Asp-Asp-Lys-beta-naphthylamide, and was inhibited strongly by various serine proteinase inhibitors. Furthermore, it was also strongly inhibited by E-64 [L-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane], a cysteine proteinase inhibitor. Substrate specificity studies involving various synthetic peptides indicated that acidic residues at the P2, P3, and/or P4 positions are especially favorable for maximal activity, but are not absolutely necessary, at least in the cases of peptide substrates.

Animals↗
PubMed1999

Comparison of the effects of convulsant and depressant barbiturate stereoisomers on AMPA-type glutamate receptors.

BACKGROUND: Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system. Although barbiturates have been shown to suppress the AMPA receptor-mediated responses, it is unclear whether this effect contributes to the anesthetic action of barbiturates. The authors compared the effects of depressant [R(-)] and convulsant [S(+)] stereoisomers of 1-methyl-5-phenyl-5-propyl barbituric acid (MPPB) on the AMPA and gamma-aminobutyric acid type A (GABA(A)) receptor-mediated currents to determine if the inhibitory effects on AMPA receptors correlate to the in vivo effects of the isomers. METHOD: The authors measured whole-cell currents in the rat cultured cortical neuron at holding potential of -60 mV. Kainate 500 microM was applied as the agonist for AMPA receptors. Thiopental (3-300 microM), R(-)-MPPB or S(+)-MPPB (100-1,000 microM) was coapplied with kainate under the condition in which the GABA(A) receptor-mediated current was blocked. Effects of MPPB isomers on the current elicited by GABA 1 microM were studied in the separate experiments. RESULTS: Thiopental inhibited the kainate-induced current reversibly and in a dose-dependent manner, with a concentration for 50% inhibition of 49.3 microM. Both R(-)-MPPB and S(+)-MPPB inhibited the kainate-induced current with a little stereoselectivity. R(-)-MPPB was slightly but significantly more potent than S(+)-MPPB. In contrast, R(-)-MPPB enhanced but S(+)-MPPB reduced the GABA-induced current. CONCLUSIONS: Both convulsant and depressant stereoisomers of the barbiturate inhibited the AMPA receptor-mediated current despite of their opposite effects on the central nervous system in vivo. Although thiopental exhibited a considerable inhibition of AMPA receptors, the results suggest that the inhibition of AMPA receptors contributes little to the hypnotic action of the barbiturates.

Animals↗
PubMed1999

Augmented enhancement of in vitro production of inflammatory cytokines in peripheral blood mononuclear cells in patients undergoing simultaneous resection of the liver and gastrointestinal tract.

OBJECTIVE: To determine changes in the production of inflammatory cytokines and acute-phase proteins, and in the priming of peripheral blood mononuclear cells (PBMC), as mechanisms for the high incidence of postoperative complications in patients who have undergone hepatectomy simultaneously with resection of the gastrointestinal tract. DESIGN: Prospective, clinical study for 3 wks after operation. SETTING: A surgical department in a university hospital. PATIENTS: Twenty-one consecutive adult patients with synchronous and metachronous hepatic metastases from gastrointestinal malignancies, curatively resected by simultaneous resection (group A, n = 9) or by hepatectomy alone (group B, n = 12), and 15 patients with gastrointestinal malignancies undergoing curative resection (group C). INTERVENTION: Peripheral venous blood samples collected before operation and on days 1, 3, 5, 7, 10, 14, and 21 after operation. MEASUREMENTS AND MAIN RESULTS: The serum and plasma levels of acute-phase proteins, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, and endotoxin were measured. The in vitro production of IL-1beta and TNF-alpha by PBMC was also determined by the stimulation of lipopolysaccharide. The incidence of postoperative complications was significantly higher in group A than in groups B and C. The serum levels of IL-6 increased significantly, with a peak at postoperative day 1 in all groups, and the peak levels of IL-6 in groups A and B were significantly higher than that in group C. The serum levels of all acute-phase proteins measured in this study (alpha1-antitrypsin, haptoglobin, and C-reactive protein) increased markedly after operation in group C (p < .05). In group A, only C-reactive protein increased after operation, but its peak level was lower than in groups B and C (p < .05). Although IL-1beta and TNF-alpha in the serum were not detectable in any of the groups during the entire study period, the lipopolysaccharide-induced in vitro production of IL-1beta and TNF-alpha by PBMC in all groups was significantly elevated after operation, with a peak at days 1 and 3 after operation, respectively. In addition, the elevation of the in vitro production of IL-1beta and TNF-alpha in group A was significantly greater than that in group C, lasting until postoperative day 5 (IL-1beta) and postoperative day 10 (TNF-alpha). The levels of plasma endotoxin increased significantly in all groups, with a peak at day 1 after operation, and the peak levels were significantly higher in group A than in groups B and C. There was a significant correlation between the peak levels of in vitro TNF-alpha production and the peak levels of plasma endotoxin (r2 = .331, p< .01). CONCLUSIONS: The augmented enhancement of the priming of PBMC as a result of surgery in patients undergoing simultaneous resection of the liver and gastrointestinal tract, together with the reduced synthesis of the acute-phase reactants and impaired host defense mechanisms, might be responsible for the high incidence of postoperative complications, possibly because subsequent exposure of primed macrophages/monocytes to triggering substances such as endotoxin and bacterial components after operation results in inappropriate production of inflammatory cytokines.

Acute-Phase Proteins↗
PubMed1999

Immature teratoma originating from the pituitary gland: case report.

OBJECTIVE AND IMPORTANCE: Recently, it has been suggested that the primary site of suprasellar germinomas is the neurohypophysis, but nongerminomatous germ cell tumors originating from the pituitary gland have been rarely reported. CLINICAL PRESENTATION: A 27-year-old man presented with panhypopituitarism, bitemporal hemianopsia, and mild right oculomotor nerve paralysis. Diabetes insipidus was not observed. The tumor was shown by magnetic resonance imaging to extend and invade bilateral cavernous sinuses, sellar and clival dura mater, and the sphenoid sinus mucosa. INTERVENTION: Transsphenoidal removal yielded a diagnosis of immature teratoma. Serum alpha-fetoprotein was prominently elevated. Magnetic resonance imaging and surgical findings of the superiorly displaced residual pituitary gland strongly suggest the pituitary origin of this rare tumor. CONCLUSION: In contrast to the neurohypophyseal germinomas, nongerminomatous malignant germ cell tumors originating from the pituitary gland tend not to be associated with diabetes insipidus and thus mimic adenomas. Evaluation of the tumor markers is necessary in young patients with cavernous sinus syndrome and invasive pituitary tumors with heterogeneous intensity revealed by magnetic resonance imaging.

Adult↗
PubMed1999

67Ga planar imaging with a low-energy collimator and scatter correction using the triple energy window method.

To improve the spatial resolution and contrast of 67Ga planar imaging, we used a low-energy collimator and two lower-energy windows with a triple-energy-window (TEW) scatter compensation method. The spatial resolution is better than with a medium-energy collimator, and the TEW method can correct for scattered photons and reduce the background counts. In a phantom study and a clinical study involving 44 patients, the images obtained by the proposed method were compared with the images obtained with a medium-energy collimator and three energy windows without scatter compensation (the conventional method). The spatial resolution and the counts were measured. Two nuclear medicine physicians interpreted the images and clinical usefulness was evaluated. The spatial resolution and contrast were improved by our proposed method. It enabled the detection of lesions in five locations in the clinical study. The counts were reduced but misreadings were not seen. We conclude that our proposed method shows a clinical advantage over the conventional method. It can be used easily and quickly with commercially available equipment and is useful in clinical practice.

Adult↗
PubMed1999

Crystallization of lipopolysaccharide from a Salmonella typhimurium semi-rough (SR) mutant.

Salmonella typhimurium SR-form lipopolysaccharide (LPS), consisting of a single repeating unit of the O-antigenic polysaccharide, linked to the R-core consisting of oligosaccharide that is, in turn, linked to lipid A, formed crystals whose shapes were hexagonal plates, discoids, and solid columns when precipitated by the addition of 2 volumes of 95% ethanol containing 375 mM MgCl2 and kept in 70% ethanol containing 250 mm MgCl2 at 4 C for 10 days. Among these crystals, the basic form is considered to be the hexagonal plates. Analyses of hexagonal plate crystals showed that they consist of hexagonal lattices with a lattice constant (a axis) of 4.62 A and longitudinal axis (c axis) of approximately 100 A. In X-ray diffraction patterns in the low-angle region, crystals of S. typhimurium SR-form LPS exhibited much less distinct reflections when compared with crystals of synthetic Escherichia coli-type lipid A. In contrast to the previous finding that S. minnesota S-form LPS possessing the O-antigenic polysaccharide does not crystallize under the same experimental conditions as used in the present study, the presence of a single repeating unit of the O-antigenic polysaccharide does not inhibit crystallization.

Carbohydrate Conformation↗
PubMed1999

Post-stroke treatment with imidapril reduces learning deficits with less formation of brain oedema in a stroke-prone substrain of spontaneously hypertensive rats.

The present study was undertaken to examine the effects of the ACE (angiotensin converting enzyme) inhibitor imidapril, on the brain, when administered after the onset of stroke in a stroke-prone substrain of spontaneously hypertensive rats (SHRSP). Learning deficits and induced lesions in the brain as well as in the kidneys and heart were investigated in detail. SHRSP were divided into two groups with or without salt loading at the age of 4 weeks. The salt loading was performed for 7-9 weeks to increase the incidence of stroke. Within 24 h after the first observation of stroke, animals were subsequently treated with 5 mg/kg imidapril orally once a day or the vehicle for up to the age of 27 weeks. Imidapril attenuated progression of neurological abnormalities such as irritability, hyperkinesia and motor dysfunction, and increased survival rate. In three-panel runway testing, learning deficits did not develop significantly in the imidapril-treated group, and was comparable to that in the non-salt-loaded/non-stroke group. Imidapril reduced oedema formation in the cortex, hippocampus and striatum, and also suppressed lesion formation in the kidneys and heart. Imidapril thus suppressed progression of neurological deficits with loss of learning ability following onset of stroke, and also suppressed formation of oedema in the brain and decreased the number of lesions in other organs. Imidapril-induced reduction of cerebrovascular damage, which presumably occurs in the brain after stroke, may account for the inhibitory effects of imidapril on lesion formation and learning impairment.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

An angiographically occult arteriovenous malformation in the medial parietal lobe presenting as seizures of medial temporal lobe origin.

We present an unusual case of a patient who was diagnosed with temporal lobe epilepsy and whose seizures were reduced markedly after excision of an angiographically occult arteriovenous malformation (AVM) located in the left medial parietal lobe. A 38-year-old man had complex partial seizures characterized by motionless staring with oroalimentary and behavioral automatisms since the age of 15 years. Magnetic resonance imaging (MRI) demonstrated a small lesion extending from the left posterior cingulate gyrus to the precuneus. There was no MRI evidence of mesial temporal sclerosis. Intracranial EEG recordings showed ictal onset from the left medial parietal lobe propagating to the medial temporal lobes. Clinical signs appeared when these discharges reached the temporal lobes. After excision of the lesion (which was histologically confirmed as an AVM), together with the marginal cortex, seizures were reduced significantly. Careful diagnostic evaluation of lesions such as the this one may reveal an epileptogenic lesion (zone) far from the region where scalp ictal discharges seem to arise. In our case, we hypothesize that false localization was due to propagation of ictal discharges from the parietal focus through the limbic system.

Adult↗
PubMed1999

Nicorandil, a potassium channel opener, abolished torsades de pointes in a patient with complete atrioventricular block.

TdP is a serious complication of AV block. We report a case of complete AV block with QT prolongation who had bouts of TdP resistant to lidocaine and isoproterenol. Temporary pacing could not be performed, because insertion of a pacing lead triggered TdP that deteriorated into ventricular fibrillation. Nicorandil, a potassium channel opener, shortened the QT interval and abolished TdP. This may suggest that potassium channel opening drugs are clinically effective against TdP associated with bradycardia-dependent QT prolongation.

Aged↗
PubMed1999

Enhanced polymorphonuclear neutrophil-mediated endothelial cell injury and its relation to high surgical mortality rate in cirrhotic patients.

OBJECTIVE: A high incidence of complications has been documented in patients with cirrhosis after operations. Recently, polymorphonuclear neutrophils (PMN) have been revealed to have the capacity to injure vascular endothelium and to cause organ damage. Furthermore, the altered function of PMN has been shown in patients with cirrhosis. However, there are few reports investigating the interaction between PMN and endothelial cells and its relation to a high incidence of postoperative complications in cirrhosis. The aim of this study was to evaluate PMN-mediated endothelial cell injury in patients with cirrhosis. METHODS: Patients were divided into two groups: those who had normal liver with metastatic liver carcinoma and those who had cirrhosis with hepatocellular carcinoma. All patients in both groups underwent hepatic resection. PMN were isolated from patients before operation. Human umbilical vein endothelial cells and PMN were cocultured after addition of phorbol myristate acetate. The release of lactate dehydrogenase (LDH) and thrombomodulin in the cocultured medium and the elastase activity in PMN suspension were measured. RESULTS: The release of both LDH and thrombomodulin in the group with cirrhosis was significantly higher than in the group with normal liver. The elastase activity was similarly higher in the group with cirrhosis than in the group with normal liver. The surgical morbidity rate was remarkably higher in the group with cirrhosis (50%) than in the group with normal liver (0%). CONCLUSIONS: This study shows that PMN have an enhanced potential to cause endothelial cell injury in patients with cirrhosis. This PMN "priming" may be responsible for the occurrence of postoperative complications in patients with cirrhosis after hepatectomy.

Adult↗
PubMed1999

Expression of p53 oncoprotein increases intratumoral microvessel formation in human salivary gland carcinomas.

P53 protein and vascular endothelial growth factor (VEGF) expression, and mean intratumoral microvessel density (IMVD) were studied by immunohistochemistry in 31 salivary gland carcinomas, consisting of 11 adenoid cystic carcinomas (AdCCs), 10 mucoepidermoid carcinomas (MECs), 7 acinic cell carcinomas (AcCCs), and 3 squamous cell carcinomas (SCCs). Cases with p53 protein in more than 20% of tumor cells were detected in one AdCC, four MECs, one AcCC, and two SCCs. Both frequency of p53 and VEGF expression, and mean IMVD, were higher in the MECs and SCCs than in the AdCCs and AcCCs. Similarly, both VEGF expression and mean IMVD were significantly higher (P<0.05) in the eight p53-positive tumors than in the 23 negative tumors. Six cases with survival periods less than 5 years showed significantly higher frequency of p53 and VEGF expression and of mean IMVD than those with longer survival periods. These results indicate that p53 expression might partly correlate with VEGF expression and mean IMVD, and be a factor in the survival of patients with salivary gland carcinomas.

Adult↗
PubMed1999

Mutational analysis of the putative fusion domain of Ebola virus glycoprotein.

Ebola viruses contain a single glycoprotein (GP) spike, which functions as a receptor binding and membrane fusion protein. It contains a highly conserved hydrophobic region (amino acids 524 to 539) located 24 amino acids downstream of the N terminus of the Ebola virus GP2 subunit. Comparison of this region with the structural features of the transmembrane subunit of avian retroviral GPs suggests that the conserved Ebola virus hydrophobic region may, in fact, serve as the fusion peptide. To test this hypothesis directly, we introduced conservative (alanine) and nonconservative (arginine) amino acid substitutions at eight positions in this region of the GP2 molecule. The effects of these mutations were deduced from the ability of the Ebola virus GP to complement the infectivity of a vesicular stomatitis virus (VSV) lacking the receptor-binding G protein. Some mutations, such as Ile-to-Arg substitutions at positions 532 (I532R), F535R, G536A, and P537R, almost completely abolished the ability of the GP to support VSV infectivity without affecting the transport of GP to the cell surface and its incorporation into virions or the production of virus particles. Other mutations, such as G528R, L529A, L529R, I532A, and F535A, reduced the infectivity of the VSV-Ebola virus pseudotypes by at least one-half. These findings, together with previous reports of liposome association with a peptide corresponding to positions 524 to 539 in the GP molecule, offer compelling support for a fusion peptide role for the conserved hydrophobic region in the Ebola virus GP.

Amino Acid Sequence↗
PubMed1999

Examination of synovial fluid and serum hyaluronidase activity as a joint marker in rheumatoid arthritis and osteoarthritis patients (by zymography).

OBJECTIVE: Hyaluronic acid (HA) is an important joint marker and the substrate for hyaluronidase (HAase). Synovial fluid (SF) and serum HAase were measured to investigate the potential use of HAase as a joint marker in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. METHODS: The subjects were 39 patients with RA and 42 patients with OA. HAase activity was measured by zymography and its relation with various parameters examined statistically. RESULTS: In RA SF a positive correlation (r = 0.458, p = 0.0186) was found between SF HAase activity and the concentration of serum C reactive protein. A positive correlation (r = 0.45, p = 0.024) was also found between SF HAase activity and platelet count in the RA group. Serum HAase activity in the RA group was significantly higher than in the OA group (p < 0.0001) and normal controls (p < 0.0001). CONCLUSION: The results suggest that SF HAase activity could be used as a marker of synovial inflammation.

Aged↗
PubMed1999

Different brain morphologies from different genotypes in a single teleost species, the medaka (Oryzias latipes)

In a teleost fish, the medaka (Oryzias latipes), many inbred strains have been established from various origins including wild populations. Brains from five genetically different strains, which had been bred and raised under the same conditions, were examined to determine whether there is intraspecific genetic variation. A total of 25 brains from the wild-type strains (HNI-II, HB11A and HB32C) and from the body-colour mutant strains (Hi3 and HO5) were fixed, and the external features of the brains were examined under a stereomicroscope. The differences between the HNI-II brains and the Hi3 brains were the most remarkable in the external features. In order to carry out a volumetric analysis, the brains of all strains were cut into complete serial cryostat sections. Total brain volumes and relative volumes (in % of total brain volume) of the olfactory bulb, telencephalon, optic tectum, and cerebellum were calculated in each brain using a semi-automatic image analyzer. Statistical analysis showed that significant differences in the total brain volumes and the relative volumes of these subdivisions exist not only between wild-type and mutant strains but also among wild-type strains. Thus, our results demonstrate that the strains with different genotypes possess large variation in brain morphology. This is the first report to demonstrate that there exists intraspecific genetic variation in the gross brain morphology of a wild-type vertebrate.

Animals↗