Search PubMed⌕ Search

Biomedical subjects

H Otsuka

Publications and source records attributed to H Otsuka.

At least 73 records · Page 4Linked to original sources

Immunogenic properties of a bovine herpesvirus-1 (BHV-1) recombinant expressing major pseudorabies virus (PrV) glycoproteins in combination.

A recombinant bovine herpesvirus type 1 (BHV-1), designated BHV-1/TF17-1, which expresses pseudorabies virus (PrV) glycoproteins gB, gC, gD, gE and gI in combination was constructed. To test the protective immunity, 10 mice were inoculated with BHV-1/TF17-1 and three weeks later 10 mice were intraperitoneally (i.p.) challenged with 20 LD50 virulent PrV (YS-81). BHV-1/TF17-1 protected all the mice from the PrV lethal challenge while all the control mice died in around 3 days. Mice vaccinated with BHV-1/TF17-1 acquired high PrV-neutralizing antibody titers and demonstrated strong delayed type hypersensitivity responses and moderate in vitro lymphocyte proliferative responses to PrV antigen. Since the major PrV glycoproteins were integrated into virions (probably into viral envelope), BHV-1/17-1 was neutralized with anti-PrV antiserum. However, the susceptibility of BHV-1/TF17-1 to anti-PrV antiserum is 2- to 4-fold lower than that of PrV vaccine lines. Our results demonstrated the possibility of BHV-1/17-1 as a vaccine to protect piglets from Audjesky's disease where maternal antibodies against PrV interfere attenuated live PrV vaccines.

Animals↗

Attachment and penetration of canine herpesvirus 1 in non-permissive cells.

Canine herpesvirus 1 (CHV-1) has a relatively narrow host cell range when compared to other alphaherpesviruses. The early events of CHV-1 infection in a permissive Madin-Darby canine kidney (MDCK) and non-permissive cell lines. In order to quantify attachment and penetration, were investigated quantitative competitive PCR (QCPCR) method was established for quantitation of CHV-1 DNA. In all non-permissive cells tested, no significant decrease in viral attachment was observed. When CHV-1 was treated with heparin, viral attachment to MDCK cells was reduced by 25% of the input CHV-1 attached to MDCK cells even in the presence of 50 microg/ml heparin. However, the attachment of CHV-1 to non-permissive cells was severely impaired by heparin treatment. In permissive MDCK cells, about 80% of attached CHV-1 penetrated into cells. However, only 4-10% of CHV-1 attached to non-permissive cells penetrated into cells. Our data indicated that CHV-1, like other herpesviruses, attached to permissive MDCK cells through two mechanisms: the first one is through the interaction mediated by heparan sulfate (HS) on the cell surface and the second involves unidentified viral component and the cellular receptor. In contrast, the non-permissive cells lacked the cellular receptor for the second attachment mechanism and the defect in viral penetration into non-permissive cell might be related to the lack of the cellular receptor.

Animals↗

Effect of age on cerebral venous circulation disturbances in the rat.

OBJECT: Mild cerebral venous circulation disturbances (CVCDs) in aged patients are frequently known to cause unexpectedly severe postoperative complications in neurosurgical practice. The object of the present study was to determine whether there are age-related differences involved in vulnerability to CVCDs. METHODS: Thirty-eight male Wistar rats were used. A single cortical vein with a 100-microm diameter was occluded photochemically by using rose bengal dye and fiberoptic illumination in young (Group Y, 19 animals aged 10-14 weeks) and aged (Group A, seven animals aged 80-100 weeks) rats. Five young and seven aged animals served as sham-operated controls. Regional cerebral blood flow (rCBF) was determined from local CBF, which was measured at 25 (5 x 5) identical locations, with the occluded vein located central to the scanning field, by using a laser Doppler scanning technique every 15 minutes for 90 minutes after venous occlusion. The cerebral venous flow pattern was examined using fluorescence angiography until 90 minutes after occlusion. Histological specimens were examined 24 hours after occlusion. In Group Y, rCBF did not change significantly after venous occlusion. However, in Group A, rCBF decreased rapidly beginning 15 minutes after occlusion. Significant intergroup differences were observed 30, 60, and 90 minutes after occlusion. Venous flow arrest, which resulted in venous infarct, was observed on angiography 90 minutes after occlusion in two (10.5%) of 19 young and six (85.7%) of seven aged rats. The venous thrombus in Group A rats was significantly larger than that in Group Y rats 90 minutes after occlusion. Venous infarction was seen in all aged rats (100%) and in six young rats (31.6%); the infarct size, expressed as a percentage of the size of the ipsilateral hemisphere, was significantly larger in aged rats than in young rats. CONCLUSIONS: This study demonstrated an age-related increase in the rate and size of venous infarct following vein occlusion, suggesting that the greater vulnerability to CVCDs in the aged brain might be attributed to early and extensive hypoperfusion of circumscribed brain areas drained by the occluded vein. The larger thrombus formation in aged animals indicates that a shift in the thrombogenetic/thrombolytic equilibrium is responsible for the observed effect.

Aging↗

Regional cerebral blood flow after status epilepticus.

Two patients with status epilepticus due to specific conditions were examined using MRI and stable Xe/CT CBF. [Case 1] A 30-year-old woman developed a grand mal seizure during delivery. She was comatose, and MRI revealed abnormal high intensity areas bilateral basal ganglia, compatible with eclampsia. Regional CBF was decreased in bilateral occipital lobes and right basal ganglia. Six days after onset. Regional gray matter flow was increased, especially in the thalami and basal ganglia. [Case 2] The patient is a 31-year-old male diagnosed with temporal lobe epilepsy since 10 years. At the onset, he had a prolonged right hemiconvulsion followed by generalized tonic-clonic convulsion. MRI 13 days after onset showed left hemispheric edematous swelling of gray matter. Stable Xe/CT 3 weeks after onset demonstrated increased cortical CBF corresponding to edematous area. The results suggested that regional CBF decreased immediately after status epilepticus and then increased for 1-3 weeks in the interictal period. We speculate that the energy debt incurred during prolonged seizure causes relative ischemic condition in the neurons, with the increase in CBF resulting from accelerated energy production for a long period.

Adult↗

[Pathogenesis of animal herpesviruses to human].

More than 90 spices of herpes viruses have been isolated from wide variety of non-human animals. Among these herpes viruses, only B virus (Cercopithecine herpesvirus 1), the natural host of which is macaque monkey, is severely pathogenic to human. B virus infects human through handling infected monkey tissues or by injury caused by infected monkey, and severe encephalitis ensues. However, in 1997 mucocutaneous infection without injury was reported. The genome structure and immunogenic property of B virus is similar to those of human herpesvirus(HSV). And pathogenecity of B virus to monkey is also similar to that of HSV to human. Although the natural host of pseudorabiesvirus (Suid herpesvirus 1) is swine, it infects wide range of animals and causes severe nervous symptoms. However, the pathogenicity to human is controversial.

Animals↗

[Asystole during electroconvulsive therapy in a patient with depression and myasthenia gravis].

A 44-yr-old woman presented with major depression. She was scheduled to receive electroconvulsive therapy under anesthetic care because of drug-induced leukopenia. Her significant past medical history was myasthenia gravis. She had been treated with thymectomy and pyridostigmine. She showed no evidence of muscle weakness while receiving the medication. After preanesthetic assessment, pyridostigmine was continued and routine anesthetics were chosen. Under 100% oxygen inhalation, thiamylal and suxamethonium were administered intravenously. Alternate current was delivered for 5 seconds, which induced seizure satisfactorily. However, asystole lasted for 10 seconds during the procedure. Spontaneous beating appeared followed by tachycardia and bigemina. Normal sinus rhythm returned four minutes later. She recovered smoothly, and showed no evidence of confusion nor muscle weakness. We speculated that pyridostigmine potentiated the ECT-induced vagal reflex and provoked asystole. In the following session, we pretreated her with intravenous atropine prior to thiamylal and suxamethonium. Although the current delivery increased RR-interval up to 1.2 seconds, neither asystole nor serious tachyarrhythmia occurred. Seven sessions of ECT relieved her psychiatric symptoms uneventfully. We presented a case of depression for which ECT was applied. Asystole with ECT seems associated with administration of pyridostigmine for the treatment of myasthenia gravis. Pretreatment with atropine can prevent asystole without inducing hazardous tachyarrhythmia.

Adult↗

Modifying effects of a mixture of acetaminophen, aspirin, dipyrone and ethenzamide on a multiorgan initiation model and its carcinogenicity in male F344 rats.

Six-week-old male F344 rats were given a mixture of 0.01% diethylnitrosamine, 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine and 0.02% N-methyl-N'-nitro-N-nitrosoguanidine in their drinking water for 1 week. When 0.8%, 0.4%, or 0% of a mixture of non-steroidal anti-inflammatory drugs (NSAIDs) (acetaminophen, aspirin, dipyrone plus ethenzamide) was given after treatment with initiators in their food from weeks 2 to 68, the incidences of liver cell tumors in the rats were 68% (P < 0.001), 25% and 8%, respectively, but those of other tumors were not different. Administration of NSAIDs from weeks 2 to 104 without initiators showed no carcinogenicity. From the results of medium-term liver bioassay, it was suggested that dipyrone and ethenzamide had promoting effects and acetaminophen had an inhibitory effect on rat hepatocarcinogenesis.

Acetaminophen↗

Modelling of the ischemic penumbra.

What happens to the ischemic penumbra--defined as a territory of critically reduced blood flow in the close neighborhood of an ischemic core--determines outcome after stroke. Currently the pathophysiology of the penumbra is studied predominantly in rat models with occlusion of the middle cerebral artery. Here we propose two other rat models with distinct advantages. One produces a large territory of critical flow reduction in the cortex of one hemisphere without presence of an infarct core: this model is suited to study mediator mechanisms that may transform the penumbra into necrotic tissue. It is produced by occluding one carotid artery and in addition reducing arterial pressure to 50 mm Hg using the hypobaric hypotension technique. Cortical flow is assessed by laser Doppler scanning. The second mode involves the photochemical occlusion of two adjacent cortical veins and goes along with a rather widespread reduction of cortical flow and the development of small infarcts of 2-5 mm3 infarct volume. Like the first model it is suited to administer mediators causing the infarct to grow in size, and thereby to evaluate the pathophysiologic significance of individual mediator mechanisms. In addition the model can be used to study specific therapeutic approaches.

Animals↗

Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study.

Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampus-amygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P = 0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks.

Adolescent↗

A patient with rectal cancer associated with ulcerative colitis in whom endoscopic ultrasonography was useful for diagnosis.

Endoscopic ultrasonography (EUS) was helpful for the diagnosis of rectal cancer associated with ulcerative colitis. The patient was a 38-year-old Japanese man with a 19-year history of relapsing-remitting type ulcerative colitis involving the entire colon. Routine colonoscopy revealed multiple polypoid prominences in the upper portion of the rectum. EUS revealed a hypoechoic mass in the submucosa beneath and around the polypoid lesion on the most oral side. Signet ring cells were found in a biopsy specimen from this lesion. Subtotal colectomy was performed. A depressed lesion was observed around the prominence on the most oral side; histologically, this lesion was poorly differentiated mucinous and signet ring cell carcinoma extending into the subserosa. The polypoid lesion on the most anal side was well differentiated adenocarcinoma, which was limited to the mucosa. Our findings suggest that EUS is helpful for detecting invasive cancer associated with ulcerative colitis.

Adenocarcinoma↗

Apoptosis in placentas from human T-lymphotropic virus type I-seropositive pregnant women: a possible defense mechanism against transmission from mother to fetus.

OBJECTIVE: The mechanism by which the placenta serves as the barrier against mother-to-fetus transmission of microorganisms remains to be elucidated. Programmed cell death, apoptosis, is considered a cellular defense mechanism against infection. The hypothesis of this study is that apoptosis of human T-lymphotropic virus type I (HTLV-I)-infected placental villous cells is involved in the defense mechanism against mother-to-fetus transmission of HTLV-I. METHODS: Apoptosis was compared in term placentas from eight HTLV-I-seropositive pregnant women and eight HTLV-I-seronegative pregnant women by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method. In addition, an in vitro cocultivation with an HTLV-I-infected lymphocyte cell line (MT-2 cells) was performed to examine whether placental villous cells were infected with HTLV-I and apoptosis was induced. RESULTS: The incidence of apoptosis-positive cells (nuclei) in placentas from the HTLV-I-seropositive pregnant women was higher than in the HTLV-I-seronegative pregnant women (P < .02). Cocultivation with MT-2 cells showed that trophoblast cells were able to be infected with HTLV-I and that apoptosis was induced in the placental villous cells. CONCLUSION: HTLV-I infection induces apoptosis in the placenta. We speculate that apoptosis may be involved in the defense mechanism of the placenta against mother-to-fetus transmission of HTLV-I.

Adult↗

Identification of the US3 gene product of BHV-1 as a protein kinase and characterization of BHV-1 mutants of the US3 gene.

We have identified the product of the US3 gene of bovine herpes virus type 1 (BHV-1), which is homologous to the herpes simplex virus type 1 (HSV-1) US3 protein kinase (PK) gene. The antibodies against the BHV-1 US3 gene product reacted with a 58 kDa polypeptide in BHV-1 infected cells and the 58 kDa polypeptide purified by immuno-precipitation demonstrated PK activity. Recent reports indicating that the US3 gene of HSV-1 is involved in the blockage of apoptosis in virus infected cells. As to the apoptosis in BHV-1 infected cells, we found following: (1) no apoptosis was observed in cells infected with wild type BHV-1 and the US3 mutants (2) the apoptosis induced by the osmotic shock of sorbitol treatment was blocked when cells were infected by the wild type BHV-1 (3) the US3 mutants of BHV-1 blocked the apoptosis of sorbitol treated cell, but the suppressive effect was delayed relative to that of wild type BHV-1 (4) the other BHV-1 mutants, with the intact US3 gene but with some other non-essential gene (genes) deleted behaved similar way to the US3 mutant. It is concluded that the US3 gene of BHV-1 is not directly involved in the blockage of apoptosis in infected cells.

Animals↗

Biosynthesis and interaction of glycoproteins E and I of canine herpesvirus.

In cells infected with canine herpesvirus (CHV), the mature form of glycoprotein E (gE) had a molecular weight of 94 kDa, and that of glycoprotein I (gI) had a broad range of molecular weights of 55-62 kDa. gE and gI formed a complex like gE and gI of other alphaherpesviruses. When cells were infected with the gI minus mutant of CHV (gI/Z), the mature form of the 94 kDa gE was not formed, but a 76 kDa gE polypeptide was found. Similarly, no mature gI was formed in cells infected with the gE minus mutant of CHV (gE/Z), but a 40 kDa gI polypeptide was formed. When cells were coinfected with gE/Z and gI/Z, the molecular masses of gE and gI were increased from 76 to 94 kDa and from 40 to 55-62 kDa, respectively. We constructed vaccinia virus recombinants which expressed CHV gE or CHV gI. Only when cells were coinfected with both the vaccinia recombinant which expressed gE and the vaccinia recombinant which expressed gI, gE and gI were processed into their mature forms. Our results suggest that the presence of both gE and gI is necessary for efficient processing of the precursors of gE and gI to their mature forms.

Animals↗

Growth behavior of bovine herpesvirus-1 in permissive and semi-permissive cells.

Bovine herpesvirus-1 (BHV-1) can replicate well in bovine-derived cell lines such as Madin Darby bovine kidney (MDBK) but grows poorly in hamster lung (HmLu-1). Virus replication, DNA synthesis, and immediate-early gene expression are severely restricted in HmLu-1. We compared adsorption and penetration of BHV-1 in permissive MDBK and semi-permissive HmLu-1 cells. At a low multiplicity of infection, BHV-1 attached to permissive MDBK cells twice as much as to HmLu-1. The presence of heparin inhibited the attachment of BHV-1 to MDBK cells by about 60%, but over 90% of the attachment was inhibited in HmLu-1. To investigate the penetration of BHV-1, we performed the quantitative measurement of viral DNA by quantitative competitive (QC)PCR in infected cells. In MDBK cells, virions attached to the cell surface, penetrated into the cells and were transported to the nucleus. However in HmLu-1, only a small fraction of the virions attached to the cell surface were allowed to penetrate. Our results indicated that the replication of BHV-1 in semi-permissive HmLu-1 was not dramatically restricted at one certain point but at some various stages including adsorption and penetration.

Animals↗

Antibodies produced by mice immunized with recombinant vaccinia viruses expressing two different types of a major Theileria sergenti surface antigen (p32) react with the native surface antigen.

A 32 kDa major surface antigen, p32, of Theileria sergenti at the piroplasm stage is the main target of the host immune response. The immunogenic property of the p32 varies in some strains among the population of Theileria sergenti in Japan where the Chitose type and the Ikeda type are the most common varieties. We have constructed vaccinia virus recombinants vv/p32C and vv/p32I which harbor the Chitose and Ikeda types of p32 gene, respectively. It was found that vv/p32C and vv/p32I produced type-specific p32 which did not cross react with the monoclonal antibodies (mAbs) against the other type of p32. When mice were immunized with vv/p32C and vv/p32I, antibodies against p32 were detectable 2 weeks after the immunization, and these antibodies reacted with the native surface antigen in purified T. sergenti merozoite.

Animals↗

Effects of hepatic impairment on the metabolism of fructose and 5-fluorouracil, as studied in fatty liver models using in vivo 31P-MRS and 19F-MRS.

The purpose of this study was to observe the effects of hepatic impairment on the metabolism of fructose and 5-fluorouracil (5-FU) in fatty liver models using in vivo 31P-MRS and 19F-MRS and to compare the results. In addition, we compared the results to those of other conventional tests such as laboratory examinations, imaging and pathology. Male SIc:Wistar rats were examined on BEM170/200 (4.7 T, Otsuka Electronics, USA) with 17-mm diameter surface coil. Fatty liver was induced by a choline deficient diet (CD diet) for 2 weeks. 31P-MRS were obtained for 90 min after intravenous (i.v.) injection of 1 g/kg of fructose and 19F-MRS were measured for 100 min after i.v. injection of 100 mg/kg of 5-FU. 1H-MRS and 1H-MRI were also performed. On 31P-MRS, there was no statistical difference in the time course of phosphomonoester (PME), adenosine triphosphate (ATP), and inorganic phosphate (Pi) between CD diet group and control group. On 19F-MRS, we detected high peak of fluoronucleotide (Fnct) and suppressed peak of alpha-fluoro-beta-alanine (FBAL) in CD diet group. We showed the metabolism of fructose and 5-FU by 31P-MRS and 19F-MRS, respectively. There was no difference in fructose metabolism but we observed increased fluoronucleotide and decreased a-fluoro-b-alanine in 5-FU metabolism of fatty liver. We speculate that the effects of hepatic impairment in fatty liver may be more severe on 5-FU metabolism and the increased fluoronucleotide may reflect cell proliferation.

Animals↗

Platanionosides A-C, megastigmane diglycosides from the leaves of Alangium platanifolium.

From the leaves of Alangium platanifolium var. platanifolium collected in Fukuoka Prefecture, Japan, three megastigmane diglycosides (1-3) were isolated, along with two known compounds, benzyl alcohol 7-O-beta-D-(6'-O-beta-D-xylopyranosyl)glucopyranoside and Z-hex-3-en-1-ol 1-O-beta-D-glucopyranoside. The structures of the new compounds, named platanionosides A (1), B (2), and C (3) were elucidated by spectroscopic evidence to be 3S,5R,6R,9R, 7E-megastigma-3,9-diol 3,9-di-O-beta-D-glucopyranoside, 3R,9R, 7E-megastigma-5,7-diene-3,9-diol 3,9-di-O-beta-D-glucopyranoside, and 5R,6S,7E-megastigma-3-on-7-en-9-ol 9-O-beta-D-(6'-O-beta-D-xylopyranosyl)glucopyranoside, respectively.

Chromatography, High Pressure Liquid↗