Transplantation of xenogeneic embryonic thymus to athymic nude mice induces acquisition of distorted immunity.
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Animals↗
Biomedical subjects
K Ohno
Publications and source records attributed to K Ohno.
Acute epidural hematoma developing during twist-drill craniostomy: a complication of percutaneous subdural tapping for the treatment of chronic subdural hematoma.
BACKGROUND: This case illustrates that although percutaneous subdural tapping for patients with chronic subdural hematoma (CSDH) is successful and minimally invasive, it can be complicated by acute epidural hematoma. CASE PRESENTATION: A 62-year-old woman presented with headache two months after minor head trauma. Computed tomography (CT) scanning revealed CSDH with mixed density on the right side. Prior to percutaneous subdural tapping, twist-drill craniostomy was performed at the parietal tuber. When the drill-needle reached the dura mater, the patient began to complain of headache, which was followed by altered consciousness. CT scanning disclosed acute epidural hematoma abutting the CSDH; both hematomas were evacuated by emergency craniotomy. At surgery, no definite bleeding source was identified apart from oozing on the dura mater. CONCLUSION: Hemorrhagic complications after percutaneous subdural tapping are rare. The formation of acute epidural hematoma during twist-drill craniostomy has not been reported in the literature. This complication can occur when the blunt tip of the drill-needle remains on the dura mater without penetrating into the subdural hematoma cavity.
Acute Disease↗
Antiviral activity of NMSO3 against respiratory syncytial virus infection in vitro and in vivo.
NMSO3, a sulfated sialyl lipid was evaluated for its efficacy against respiratory syncytial virus (RSV) and other myxovirus infections in cell culture. The median effective concentration (50% effective concentration, EC(50)) of NMSO3 against replication of the Long strain of RSV in HEp-2 cells was 0.2 and 0.32 microM by optical ELISA and the plaque reduction method, respectively. On the other hand, the corresponding values for ribavirin were 10.5 and 11.2 microM, respectively. NMSO3 showed potent activity against other laboratory strains as well as fresh clinical isolates of RSV, and the average EC(50) was similar to that for Long strain. NMSO3 exhibited minimal cytotoxicity against HEp-2, MDCK, HMV-2 and Vero cells for which the median cytotoxic concentration (CC(50)) was more than 685 microM. The selectivity index [SI=(CC(50) for HEp-2/EC(50))] of NMSO3 for RSV exceeded 2978 and that of ribavirin was 6. The EC(50) of NMSO3 against influenza virus (FluV) A (H3N2) was 23.8 by the MTT method using HMV-2 cells, and 17.8 microM by the TCID(50) method using MDCK cells. NMSO3 did not inhibit replication of influenza B virus, parainfluenza virus type 2 and canine distemper virus at 103 microM. NMSO3 inhibited RSV infection of HEp-2 cells when it was added between 0 and 1.5 h after virus infection. By a temperature shift experiment during the period of contact between the virus and cells, NMSO3 inhibited both the binding of RSV to the cells and its penetration into the cells. Prophylactic and therapeutic efficacy of NMSO3 against RSV infection in cotton rats was examined. Intraperitoneal administration of 100 mg/kg per day of NMSO3 to cotton rats from 1 day before or 1 h after to 3 days after the RSV infection, once a day every day, decreased the RSV titer in lungs to 10(-1.26) to 10(-1.63) compared to the control rats which were infected with RSV and left untreated.
Animals↗
Interruption of supramammillohippocampal afferents prevents the genesis and spread of limbic seizures in the hippocampus via a disinhibition mechanism.
In this study we describe the preventive effect of interruption of the supramammillohippocampal afferents on the Fos expression in the forebrain and epileptic discharges in the hippocampal electroencephalogram in rat model of kainic acid-induced limbic seizure. Little was known about the contribution of different degrees of neural activity of hippocampal principal cells to the genesis and spread of limbic seizures in the forebrain structures. Following kainic acid injection to the amygdala with or without concurrent injection of muscimol to the supramammillary nucleus, behavioral changes and electroencephalograms were observed in freely moving rats. The animals were processed for Fos immunocytochemical analysis at several time points. The latest expression of Fos at 2h was seen in hippocampal CA1-CA3, ventrolateral thalamic nuclei and mediodorsal caudate putamen, while the early Fos expression at 0.5h was seen in the piriform, entorhinal and other cortices, the thalamic midline nuclei and hypothalamic nuclei. Muscimol injection to the supramammillary nucleus prevented Fos expression in the CA1-CA3 region and reduced that in the forebrain regions with the latest Fos expression, but did not affect Fos expression in other forebrain regions with early Fos expression. This treatment also eliminated epileptic discharges and attenuated all waves in hippocampus. These findings indicate that an acute interruption of the facilitatory hypothalamic afferents by intrasupramammillary injection of muscimol may cause the inactivation of the disinhibition mechanism for hippocampal throughput at the dentate gyrus, resulting in the blockade of the genesis and spread of limbic seizures in the hippocampus.
Afferent Pathways↗
Well-defined oligosaccharide-terminated polymers from living radical polymerization.
beta-cyclodextrin has been transformed into an initiator for copper(I)-mediated living radical polymerization via successive acetylation, ring opening, and condensation reactions. This glycoinitiator has been successfully used to prepare a range of methacrylate polymers, which show all characteristics of living polymerization. Poly(methyl methacrylate) is prepared with an Mn of 10,100 g/mol (theoretical Mn = 10,900) and polydispersity of 1.09. Excellent first-order kinetics and an evolution of mass with time are presented. Hydrophilic polymers based on poly(ethylene glycol), glucose and tertiary amine monomers are successfully prepared with terminal maltoheptose units. Polymerization of styrene results in a broadening of the polydispersity to 1.48 while maintaining good control over the Mn. The acetyl protecting groups on the maltoheptose terminal unit are easily removed in all cases to give the hydroxylated sugar, as shown by NMR. These results demonstrate the applicability of utilizing glycoinitiators as a new, versatile route to a wide range of glycopolymers. The polymerization chemistry is inert to the sugar functionality allowing glyco units to be precisely placed within a synthetic macromolecule with all the associated advantages of living polymerization.
Carbohydrate Sequence↗
Validity, reliability and acceptability of the Japanese version of the General Well-Being Schedule (GWBS).
The General Well-Being Schedule (GWBS) is a widely used, self-administered questionnaire to measure subjective well-being. It contains 18 items and was originally hypothesized to have six domains; however, the following studies suggest other factorial models. We devised the schedule's Japanese edition following the standard procedure and tested its psychometric properties considering Japanese cultural characteristics. Subjects were 1224 middle-aged participants undergoing health checkups in Adachi, Tokyo. The reliability of the original version was high: alpha coefficient, 0.90; test-retest Pearson's correlation coefficient, 0.81; and intra-class correlation coefficient, 0.85. Confirmatory factor analyses supported the structural validity of the 6-factor, the following 3-factor and 4-factor models (goodness of fit index: 0.932, 0.946 and 0.937, respectively). A new 3-factor model developed after the exclusion of item 11, which had no correlation with the other variables, was proved to have a higher fitness index (0.958) than the other models. This 17-item version showed adequate reliability (alpha coefficient, 0.91; test-retest Pearson's correlation coefficient, 0.81; and intra-class correlation coefficient, 0.85) and concurrent validity compared with the General Health Questionnaire, State-Trait Anxiety Inventory, Center for Epidemiologic Studies Depression Scale, Self-rating Depression Scale and Profile Of Mood State (correlation coefficients: -0.75 to -0.53). The median time required to complete the schedule was five minutes. Completing this instrument was easy for 80% of the subjects. These findings attest to the adequacy of the 17-item Japanese GWBS for the comprehensive assessment of individual inner state.
Adult↗
Cloning and sequencing of canine MAGE cDNA.
Melanoma antigens (MAGE) are regarded to induce tumour-specific immune response and thought to be potential therapeutical agents for cancer immunotherapy. We hereby report the canine MAGE cDNA cloned from the testis of a beagle dog. Canine MAGE cDNA is 1,455 base pair (bp) nucleotides in length, and contains an open reading frame (ORF) of 1,137 bp nucleotides encoding a protein of 378 amino acids. The predicted amino acid sequence has 22-49% of homology with other MAGE proteins. mRNA transcripts of canine MAGE were detected only in the melanoma and testis and not in other normal tissues of adult dog by reverse transcriptase-polymerase chain reaction (RT-PCR), indicating that the expression pattern of canine MAGE mRNA is similar to that of the MAGE family genes in tumor and normal tissues.
Animals↗
Effects of anticonvulsants on local anaesthetic-induced neurotoxicity in rats.
The effects of various anticonvulsants on local anaesthetics procaine- and lidocaine-induced convulsions were investigated in rats. Pretreatment with diazepam (2.5-5 mg/kg, intraperitoneally) and clonazepam (5-10 mg/kg, intraperitoneally) completely protected the rats against both local anaesthetic-induced convulsions. Phenobarbital (12.5-50 mg/kg, subcutaneously) also significantly decreased the incidence of both convulsions and prolonged their latencies. Carbabazepine (10-40 mg/kg, intraperitoneally) did not completely repress both convulsions, but it prolonged their latencies. Phenytoin (5-20 mg/kg, intraperitoneally) and primidone (30-60 mg/kg, intraperitoneally) markedly enhanced both local anaesthetic-induced convulsions, as shown by shortening of latency and increase in mortality. Valproate (100-200 mg/kg, intraperitoneally) produced a protective effect against procaine-induced convulsions, while it strongly enhanced lidocaine-induced convulsions. These results suggest that the benzodiazepines are effective drugs to prevent neurotoxicity induced by local anaesthetics, while phenytoin and primidone potentiate them.
Anesthetics, Local↗
Effect of ovariectomy on bone remodeling adjacent to hydroxyapatite-coated implants in the tibia of mature rats.
PURPOSE: The purpose of this study was to examine the effects of estrogen deficiency on bone remodeling adjacent to implants in the tibia of mature rats. MATERIALS AND METHODS: Hydroxyapatite-coated implants were placed bilaterally in the proximal metaphysis of the tibia of 18 female Wistar rats (48 weeks old), and ovariectomy was performed 168 days later. As a control, sham ovariectomy was performed in a similar group of 18 rats. Six animals from each group were killed at 28, 84, and 168 days after ovariectomy. Undecalcified sections were prepared, and changes in the bone tissue around the implants were evaluated histologically. Histomorphometric measurements were made with a computer-based image analyzer to quantify the unit bone mass around each implant and the amount of implant-bone contact. RESULTS: In the cortical bone area, ovariectomy induced only a slight decrease in bone contact with the implant, compared with that in the sham-operated rats. However, both the bone volume around the implant and implant-bone contact were significantly decreased in the cancellous bone area in ovariectomized rats compared with the sham-operated rats. CONCLUSION: Thinning of the bone trabeculae holding dental implants may occur with estrogen deficiency.
Animals↗
Fundamental gating mechanism of nicotinic receptor channel revealed by mutation causing a congenital myasthenic syndrome.
We describe the genetic and kinetic defects in a congenital myasthenic syndrome due to the mutation epsilonA411P in the amphipathic helix of the acetylcholine receptor (AChR) epsilon subunit. Myasthenic patients from three unrelated families are either homozygous for epsilonA411P or are heterozygous and harbor a null mutation in the second epsilon allele, indicating that epsilonA411P is recessive. We expressed human AChRs containing wild-type or A411P epsilon subunits in 293HEK cells, recorded single channel currents at high bandwidth, and determined microscopic rate constants for individual channels using hidden Markov modeling. For individual wild-type and mutant channels, each rate constant distributes as a Gaussian function, but the spread in the distributions for channel opening and closing rate constants is greatly expanded by epsilonA411P. Prolines engineered into positions flanking residue 411 of the epsilon subunit greatly increase the range of activation kinetics similar to epsilonA411P, whereas prolines engineered into positions equivalent to epsilonA411 in beta and delta subunits are without effect. Thus, the amphipathic helix of the epsilon subunit stabilizes the channel, minimizing the number and range of kinetic modes accessible to individual AChRs. The findings suggest that analogous stabilizing structures are present in other ion channels, and possibly allosteric proteins in general, and that they evolved to maintain uniformity of activation episodes. The findings further suggest that the fundamental gating mechanism of the AChR channel can be explained by a corrugated energy landscape superimposed on a steeply sloped energy well.
Cell Line↗
Specific cell targeting for delivery of toxins into small-cell lung cancer using a streptavidin fusion protein complex.
New modalities of treatment for small-cell lung cancer (SCLC) are needed, because the majority of patients continue to die of disseminated disease despite an initial response to conventional chemotherapy. Abnormal surface expression of the neural-cell adhesion molecule (NCAM) has been noted to be highly associated with SCLC. We examined the ability and efficiency of a streptavidin-Protein A (ST-PA) fusion protein complexed with an anti-NCAM monoclonal antibody (Mab) to transfer biotinylated beta-galactosidase into human SCLC cell lines NCI-H69, NCI-H526, and NCI-H446. When the surface molecule NCAM was targeted with this system, more than 99% of the targeted cells internalized and exhibited beta-galactosidase activity. In addition, we evaluated cytotoxic activity against SCLC lines NCI-H69 and NCI-H526 by efficient delivery of biotinylated glucose oxidase using the same ST-PA/anti-NCAM Mab complex. Cytotoxicity of the transduced cells (SCLC) was 10-fold and 100-fold greater, respectively, than the glucose oxidase control. This system could be widely applied for specific therapy of cancer cells by targeting unique surface molecules (antigens) using the corresponding Mab/ST-PA complex to transfer a variety of effector molecules; e.g., immunotoxic compounds, into target cells with a high degree of efficiency and specificity.
Animals↗
Genotype-phenotype relationship of Niemann-Pick disease type C: a possible correlation between clinical onset and levels of NPC1 protein in isolated skin fibroblasts.
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Adolescent↗
Clonality analysis of various hematopoietic disorders in cats naturally infected with feline leukemia virus.
The clonality analysis of the bone marrow cells was carried out by detecting the integrated proviruses of feline leukemia virus (FeLV) to understand the pathogenesis of FeLV-associated hematopoietic disorders in cats. Bone marrow cells from 4 cases with acute myeloid leukemia (AML), 9 cases with myelodysplastic syndromes (MDS), 2 cases with pure red cell aplasia (PRCA) and 3 healthy carriers infected with FeLV were subjected to Southern blot analyses using an exogenous FeLV probe. Clonal hematopoiesis was found in all the cases with AML and in 6 of the 9 cases with MDS, but not in the cases with both PRCA and healthy carriers infected with FeLV. In the 2 cases with MDS, it was thought that the same clones of the hematopoietic cells might proliferate before and after the progression of the disease irrespective of the changes of the hematological diagnoses by cytological examination. This study indicates that MDS in cats is a disease manifestation as a result of clonal proliferation of hematopoietic cells and can be recognized as a pre-leukemic state of AML.
Animals↗
Experimental sensitization with Japanese cedar pollen in dogs.
Japanese cedar pollinosis is a type I allergic disease mediated by immunoglobulin E (IgE) antibodies to Japanese cedar (Cryptomeria japonica) pollen antigen (CPAg). By using 22 dogs consisting of 20 dogs aged 3 months and 2 dogs aged 3 years, immunization was performed by subcutaneous injections of CPAg with aluminum hydroxide gel. Variable levels of CPAg-specific IgE antibody response were detected in 21 of the 22 immunized dogs two weeks after the second immunization. This study provided an experimental sensitization system with CPAg in dogs, which will be useful for further immunological studies on Japanese cedar pollinosis.
Animals↗
In vivo and in vitro tests showing sensitization to Japanese cedar (Cryptomeria japonica) pollen allergen in atopic dogs.
Using both in vivo and in vitro tests, dogs with atopic dermatitis were examined for sensitization with Japanese cedar (Cryptomeria japonica, CJ) pollen allergen. Ten dogs with clinical manifestation of atopic dermatitis were shown to be sensitized to CJ pollen based on the results of intradermal skin test and serum antigen-specific IgE test. In vitro lymphocyte stimulation test showed blastogenic response after stimulation with crude antigen of CJ pollen in all of the 5 cases examined. The peripheral leukocytes showed increased histamine release after stimulation with crude antigen of CJ pollen in 2 cases examined. These data indicate that a proportion of dogs with atopic dermatitis is sensitized to CJ pollen in a cell-mediated manner and show immediate phase reaction of type I hypersensitivity.
Allergens↗
Inhibitory effect of apple pectin and culture condensate of Bifidobacterium longum on colorectal tumors induced by 1,2-dimethylhydrazine in transgenic mice harboring human prototype c-Ha-ras genes.
The number and tumor score of colorectal tumors induced by 1,2-dymethylhydrazine in transgenic (Tg) mice carrying human c-Ha-ras genes were significantly reduced by ingestion of apple pectin (AP) or a culture condensate of Bifidobacterium longum (MB) when compared with a control diet. There was no statistical difference in the incidence of colorectal tumors in Tg mice between the AP or MB diet and the control diet. This study demonstrated that Tg mice are a useful tool for screening inhibition of colorectal tumors by functional foods.
1,2-Dimethylhydrazine↗
Changes in local cerebral blood flow, glucose utilization, and mitochondrial function following traumatic brain injury in rats.
The pathophysiology of secondary brain damage following experimental traumatic brain injury was investigated by measuring local cerebral blood flow (lCBF), local cerebral glucose utilization (lCGU), and activity of succinate dehydrogenase (SDH), which is a mitochondrial enzyme of the tricarboxylic acid cycle, in the rat brain after moderate lateral fluid percussion injury. Measurements used autoradiography for lCBF and lCGU with [14C]iodoantipyrine and [14C]2-deoxyglucose, respectively. Regional SDH activity was determined using quantitative imaging of formazan produced from 2,3,5-triphenyl tetrazolium chloride by SDH. lCBF decreased at 1 hour after injury and was significantly lower than the preinjury level in almost all regions of both hemispheres at 6 and 24 hours, and remained low at 2 weeks. lCGU increased 1 hour after injury but was significantly decreased at 6 and 24 hours, and at 2 weeks in most regions of both hemispheres. The ipsilateral hemisphere showed a significant decrease in the activity of SDH in the cortices, hippocampus, thalamus, and caudate/putamen, most conspicuously 72 hours after injury, whereas no significant decrease was observed in the contralateral hemisphere at any time. Necrosis in the injured cortex and reduction of the number of neurons in the ipsilateral hippocampus were observed 2 weeks after injury. The present study showed that a decrease in lCBF and mitochondrial dysfunction occur with glucose hypermetabolism around 1 hour after lateral fluid percussion injury, and that lCBF, lCGU, and mitochondrial function all deteriorate after 6 hours. This suggests that lCBF and cellular metabolism may change dynamically during the several hours following traumatic brain injury, and afterwards neuronal damage may result in an irreversible change in the areas with depressed glucose hypermetabolism in the early period after injury in combination with mitochondrial dysfunction.
Animals↗
The spectrum of mutations causing end-plate acetylcholinesterase deficiency.
The end-plate species of acetylcholinesterase (AChE) is an asymmetric enzyme consisting of a collagenic tail subunit composed of three collagenic strands (ColQ), each attached to a tetramer of the T isoform of the catalytic subunit (AChE(T)) via a proline-rich attachment domain. The principal function of the tail subunit is to anchor asymmetric AChE in the synaptic basal lamina. Human end-plate AChE deficiency was recently shown to be caused by mutations in COLQ. We here report nine novel COLQ mutations in 7 patients with end-plate AChE deficiency. We examine the effects of the mutations on the assembly of asymmetric AChE by coexpressing each genetically engineered COLQ mutant with ACHE(T) in COS cells. We classify the newly recognized and previously reported COLQ mutations into four classes according to their position in ColQ and their effect on AChE expression. We find that missense mutations in the proline-rich attachment domain abrogate attachment of catalytic subunits, that truncation mutations in the ColQ collagen domain prevent the assembly of asymmetric AChE, that hydrophobic missense residues in the C-terminal domain prevent triple helical assembly of the ColQ collagen domain, and that other mutations in the C-terminal region produce asymmetric species of AChE that are likely insertion incompetent.
Acetylcholinesterase↗