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Biomedical subjects

T Komatsu

Publications and source records attributed to T Komatsu.

At least 181 records · Page 10Linked to original sources

Traumatic arteriovenous fistula treated by superselective embolisation with microcoils: case report.

A 27-year-old man with a traumatic direct dural arteriovenous fistula (DAVF) was treated using embolisation microcoils. He had suffered blunt trauma to the head while drunk and was aware of no neurological deficit. A few days after the accident, however, he noticed a bruit in the right temple. Angiography demonstrated a direct DAVF fed by the right middle meningeal artery and draining into a right temporal dural vein and the ipsilateral cavernous sinus. A Tracker-18 catheter was passed without difficulty through the fistula and the draining vein was then embolised from distal to proximal with microcoils, and finally the fistula was occluded with microcoils, resulting in total obliteration of the fistula. Immediately after the embolisation, the patient could no longer hear the bruit. Thus, when a microcatheter can be introduced into the draining vein, microcoils can be used as emboli in the treatment of direct DAVF.

Adult↗

Differential effects of ketamine and midazolam on heart rate variability.

Alterations in autonomic activity caused by anaesthesia can be assessed by spectral analysis of heart rate variability (HRV). This study examined the effects of ketamine and midazolam on HRV. Thirty patients of ASA PS 1 were studied. Fifteen were given ketamine (2 mg.kg-1) and 15 received midazolam (0.3 mg.kg-1), iv. The RR intervals of ECG were measured before and after induction of anaesthesia for ten minutes during spontaneous respiration. Power spectral density of the data was computed using fast Fourier transform. The spectral peaks within each measurement were calculated: low frequency area (LF, 0.04-0.15 Hz), high frequency area (HF, 0.15-0.5 Hz), and total power (TP, 0.04-0.5 Hz). Normalized unit power was derived as follows: low frequency area (nuLF): LF/TP x 100%, high frequency area (nuHF): HF/TP x 100%. Both ketamine and midazolam caused reductions in all measurements of HRV power (P < 0.05). However, ketamine increased nuLF from 64 +/- 14% to 75 +/- 13% (P < 0.05) and decreased nuHF from 36 +/- 14% to 25 +/- 13% (P < 0.05), while midazolam decreased nuLF from 66 +/- 15% to 54 +/- 14% (P < 0.05) and increased nuHF from 34 +/- 15% to 46 +/- 14% (P < 0.05). These results documented that both ketamine and midazolam reduced the total power and all frequency components of power in spite of their opposing effects on autonomic nervous activity. However, normalized unit power showed the expected sympathetic activation with ketamine and sympathetic depression with midazolam since ketamine increased nuLF and midazolam decreased nuLF.

Adult↗

Effects of MCI-225 on memory and glucose utilization in basal forebrain-lesioned rats.

The effects of MCI-225 on amnesia, the cerebral glucose metabolism, and choline acetyltransferase (ChAT) activity in basal forebrain (BF)-lesioned rats were studied in comparison with those of tacrine. Bilateral BF lesions with ibotenic acid impaired the performance in passive avoidance (PA) tasks. Single administration of MCI-225 (10 mg/kg, PO) after a 2-week postoperative recovery period, increased the escape latencies in the PA task, but was not statistically significant. Repeated administration of MCI-225 (0.3 and 1 mg/kg, PO for 6 days) significantly reversed the PA failure. The BF-lesioned rat exhibited a marked decrease in the local cerebral glucose utilization (LCGU) in the frontal cortex, parietal cortex, and caudate-putamen. MCI-225 (1 mg/kg, PO for 5 days) significantly ameliorated the reduction of the LCGU in the parietal cortex. MCI-225 did not change the decrease in the cortical ChAT activity induced by the BF lesion. Repeated administration of tacrine reversed the PA failure (0.3 mg/kg, PO) but failed to prevent the decrement in the LCGU and the ChAT activity. These results suggest that MCI-225 could be effective in the treatment of senile dementia of the Alzheimer type, which is accompanied with both deficit in the BF-cortex cholinergic neuron and cerebral glucose hypometabolism.

Animals↗

Viremia induced by influenza virus.

A mouse model of influenza A/PR/8 virus infection was adopted to investigate the blood and various tissues of intranasally infected mice for the presence of viral RNA by using the nested polymerase chain reaction. The nucleoprotein gene was detected in the red blood cell fraction from 1 to 5 days post-inoculation, while it was found in the lung and brain up to 14 days and in the liver, spleen, kidney, heart, and skeletal muscle up to 7 days. The virus-specific messenger RNA was transiently found in these organs. When mice received the uv-inactivated virus, viremia did not occur. The prior transfer of the hyperimmune serum prevented pneumonia but not bronchitis, and viremia was totally abolished. These results suggest: (1) viremia occurs during the acute phase of infection, (2) the virus is present in various organs and there the virus gene is transiently expressed, and (3) the virus enters the blood stream possibly through capillaries of the infected alveolar wall. Viremia may influence the pathogenesis of influenza.

Animals↗

Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression.

Alteration of expression levels of the nm23 genes has previously been correlated with metastatic status of ovarian epithelial carcinoma. To elucidate the relevance of the qualitative changes of the nm23 genes to progression of ovarian carcinoma and/or to nm23 expression levels of the tumour, 41 samples of epithelial ovarian tumours [three benign, three low malignant potential (LMP), and 35 frankly malignant tumours] were studied for mutation of the nm23-H1 and the nm23-H2 genes using single-strand conformational polymorphism (SSCP) analysis. In addition, loss of heterozygosity (LOH) at the nm23 locus on chromosome 17q was studied by CA repeat polymorphism analysis. Mutation of the K-ras gene was also analysed in the same specimens. A novel mutation of the nm23 gene was found in one case of stage III serous carcinoma without lymph model metastases. Sequencing of the subcloned mutant cDNA revealed a missense mutation from TGG to CGG at codon 133 of the nm23-H2 gene, resulting in a change from Trp to Arg. LOH at the nm23 locus was detected in 5 of 23 (21.7%) informative cases of ovarian carcinoma. Mutation of the K-ras gene was detected in 2 of 35 (5.7%) carcinomas at codons 12 and 13 respectively. There was no correlation between clinical stage or metastatic status of ovarian carcinoma and nm23 mutation, LOH at the nm23 locus or K-ras mutation. The expression levels of both the nm23-H1 and the nm23-H2 genes were lower in the tumour with nm23-H2 mutation and higher in those with K-ras mutation. This suggests that mutation of the nm23 genes and the K-ras gene affects carcinogenesis or progression of ovarian carcinoma by modulating expression of the nm23 genes.

Adult↗

In vivo induction of apoptosis by influenza virus.

Intranasal exposure of mice to influenza virus led to cell death in bronchial/bronchiolar epithelial cells, alveolar cells and lymphoid cells. These cells displayed fragmentation of nuclei and chromatin condensation. Nick end-labelling of DNA in situ confirmed that such apoptotic cells had fragmented DNA. These results suggest that the influenza virus induces apoptosis in vivo.

Animals↗

Parainfluenza virus type 1 infects olfactory neurons and establishes long-term persistence in the nerve tissue.

A mouse model of Sendai virus infection was adopted to examine the in vivo neurovirulence of parainfluenza viruses. A nested polymerase chain reaction detected the Sendai virus nucleoprotein gene in the olfactory bulbs of intranasally infected mice for at least 168 days post-infection (p.i.) and virus-specific messenger RNAs for 28 days p.i. Viral proteins were histochemically detected in some olfactory neurons for 7 days p.i. They were also found in glomeruli of the olfactory bulbs but not in the mitral cells and the tufted cells. No virus was detected in the whole brain not including the olfactory bulbs. When mice were inoculated with UV-inactivated virus, the viral RNA was present in the olfactory bulbs for a short period of 14 days, with no demonstrable viraemia. These results demonstrate that the parainfluenza virus directly accesses the central nervous system via olfactory neurons and establishes long-term persistence in the nerve tissue.

Animals↗

T cell-rich B cell lymphoma bearing Epstein-Barr virus in tumor cells: a case of IBL-T-like lesion following Lennert's lesion.

A case of T cell-rich B cell lymphoma (TCRBCL) with Epstein-Barr virus (EBV) infection in tumor cells is reported. A 50 year old male developed right cervical lymph node swelling in July 1988. Initial biopsy in April 1989 demonstrated many scattered Hodgkinoid atypical cells with Lennert's lesion. After partial remission following chemotherapy, the lymph nodes enlarged again, and a second biopsy in February 1991 showed an IBL-T-like lesion. Only a small number of Hodgkinoid atypical cells were still observed. After apparently, complete remission, the lesion soon recurred and the patient died in November 1992. Immunohistochemically the Hodgkinoid cells were positive for L26, but negative for LN2, LN3, UCHL-1, MT1, lysozyme, Ber-H2 and Leu-M1. Reactivity for immunoglobulins showed false-positive because of polyclonal staining. IgH monoclonality was detected by the polymerase chain reaction method in the first biopsied specimen, and by Southern blotting in the second biopsied snap-frozen specimen. Monoclonal TCR beta rearrangement was not detected. The Hodgkinoid atypical cells were positive for EBV-encoding RNA by in situ hybridization, and LMP-1 by immunostaining. Occasionally, EBV-bearing immunoblastic, medium sized, or small lymphocytic cells were also observed. This case indicates the possibility that EBV is related to the pathogenesis of TCRBCL.

Blotting, Southern↗

A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock.

Administration of monoclonal anti-CD3 antibody to mice treated with Propionibacterium acnes induced secretion of a high level of gamma interferon (IFN-gamma) into the circulation system, while it induced no significant release in untreated mice. In order to analyze this high-level induction of IFN-gamma in these bacterium-treated mice, we investigated the factors that might be involved. An activity that induces IFN-gamma in T cells was observed in the liver extracts of mice treated with P. acnes and subsequently challenged with lipopolysaccharide. Here, we purified an IFN-gamma-inducing factor from the liver extract to homogeneity and characterized it. Its molecular mass was 18 to 19 kDa, and its pI was 4.9. The amino acid sequence of the NH2-terminal portion was determined and shown to have no similarities to any protein in the EMBL, GenBank, and PIR data bases. The same molecule was also demonstrated in the serum factor that was previously reported to have an IFN-gamma-inducing activity and to have an apparent molecular mass of 75 kDa. Moreover, the activity of this serum factor was recovered in the fraction containing the 18- to 19-kDa protein under reducing conditions and was shown to have the same NH2-terminal amino acid sequence as that of the factor from the liver extract. In addition to the ability to induce IFN-gamma, this protein augmented T-cell proliferation and NK activity in the spleen cells. Thus, several of its biological activities were apparently similar to those of interleukin-12. These results indicated that this novel protein, which exhibited marked costimulatory activity on IFN-gamma production in vitro, was elevated vivo in response to P. acnes treatment. This factor, probably released from the producing cells by lipopolysaccharide stimuli, may be involved in the high-level induction of IFN-gamma in the P. acnes-treated mice.

Amino Acid Sequence↗

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↗

Vesicular stomatitis virus infection of the central nervous system activates both innate and acquired immunity.

Vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS) when intranasally applied. We have examined cellular inflammatory changes in the CNS following VSV infection. As early as 1 day postinfection (p.i.), astrocytes were activated in the olfactory bulb (OB). This was followed by activation of microglia, first observed in the OB at day 3 p.i. Expression of inducible nitric oxide synthase was observed in activated microglia in the OB at day 3 p.i., and increased inducible nitric oxide synthase expression coincided with decreased virus titers in tissue homogenates. Expression of major histocompatibility complex (MHC) class I molecules on astrocytes and microglial, endothelial, and ependymal cells was also rapidly induced and followed by induced expression of MHC class II molecules on astrocytes and microglial and endothelial cells. Consistent with the pattern of viral dissemination, MHC molecules were expressed temporally from the rostral-to-caudal direction. Infiltration of CD8+ cells was observed as early as 1 day p.i. in the OB. CD4+ cells were detected in the OB at day 4 p.i. Increasing T-cell infiltration coincided with decreased virus titers. In contrast, B-cell infiltration of the CNS was not detected until day 14 p.i., after the virus was cleared and mice were showing behavioral signs of recovery. Breakdown of the blood-brain barrier was detected beginning at day 6 p.i., was most severe at day 8 p.i., and was followed by full recovery. Collectively, these data show that both innate immunity (production of nitric oxide) and acquired immunity (expression of MHC molecules and T-cell infiltration) are activated following VSV infection in the CNS.

Amino Acid Oxidoreductases↗

Immunohistochemical localization of heat shock proteins HSP70 and HSP90 in the human endometrium: correlation with sex steroid receptors and Ki-67 antigen expression.

Heat shock proteins of 72 kDa and 90 kDa (HSP70, HSP90) have been suggested to be involved in the functional modulation of sex steroid receptors. We examined the immunohistochemical localization of HSP70 and HSP90 in both the functionalis and basalis layers of normal human endometrium during various phases of the menstrual cycle. Topological correlation with localization of estrogen receptors (ER), progesterone receptors (PR), and proliferation-related Ki-67 antigen was also analyzed. HSP70 was expressed in glandular cells of the basalis but not in the cells of the functionalis during the proliferative phase. In the secretory phase, however, glandular cells of both the basalis and functionalis markedly expressed HSP70. Endometrial stromal cells at the basal layer were positive for HSP70, whereas those cells in the functional layer were negative for HSP70 throughout the menstrual cycle. The topological expression of HSP70 in glandular and stromal cells of the basalis was inversely related to Ki-67 localization. Overexpression of HSP70 in the secretory glands was associated with down-regulation of ER and PR. These findings suggest that HSP70 expression is related to either hormonal regulation of cell proliferation and/or down-regulation of sex steroid receptors. HSP90 was strongly expressed in both glandular and stromal cells during the proliferative phase of the menstrual cycle; in the secretory phase, HSP90 expression was weak in both types of the cells. However, no topological difference in HSP90 expression between the basalis and the functionalis was observed.

Adult↗

[Synthesis of estimated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247). I. Synthesis of mono-hydroxylated metabolites].

The two mono-hydroxylated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of two tricyclic ketones, 9-amino-1,2,3,5,6,7-hexahydro-8H-cyclopenta[b]quinolin-8-one and 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]-quinolin-1-one, with NaBH4 afforded the corresponding racemic alcohols. The optically active mono-hydroxylated metabolites, (+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-8-ol and (+)-9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-1-ol, were obtained by optical resolution of each racemic alcohol using (+)-di-p-toluoyl-D-tartaric acid.

Aminoquinolines↗

[Synthesis of estimated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247). II. Synthesis of dihydroxylated metabolites].

The two dihydroxylated metabolites of 9-amino-2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinoline monohydrochloride monohydrate (NIK-247), which is a new drug for the treatment of dementia, were synthesized to determine their chemical structures. Reduction of the tricyclic diketone, 9-amino-2,3,6,7-tetrahydro-1H-cyclopenta[b]quinoline-1,8(5H)-dione, with equivalent molar of NaBH4, afforded the racemic two alcohols, (+/-)-9-amino-2,3,5,6,7,8-hexahydro-8-hydroxy-1H-cyclopenta[b]quinoli n-1-on e and (+/-)-9-amino-2,3,5,6,7,8-hexahydro-1-hydroxy-1H-cyclopenta[b]quinoli n-8- one. (+)-9-Amino-2,3,5,6,7,8-hexahydro-8-hydroxy-1H-cyclopenta[b]quinolin+ ++-1-one was obtained by optical resolution of the corresponding racemic hydroxyketone using (-)-di-p-toluoyl-L-tartaric acid. The optically active dihydroxylated metabolites were obtained by reduction of the (+)-8-hydroxy-1-one with NaBH4.

Aminoquinolines↗

A toluene-tolerant mutant of Pseudomonas aeruginosa lacking the outer membrane protein F.

The outer membrane protein profiles of a toluene-tolerant mutant, Pseudomonas aeruginosa, strain PAK103, were compared with those of its parent strain PAO1161. Protein F (OprF), the most abundant outer membrane protein in the parental strain PAO1161, was missing in the toluene-tolerant strain PAK103. The absence of OprF may lead to the loss of toluene diffusion across in the outer membrane of the mutant cells.

Amino Acid Sequence↗

Isolation and characterization of a hantavirus from Rattus norvegicus in a residential area of Nagoya City, Japan.

The prevalence of antibodies to hantavirus among Rattus norvegicus in Nagoya city was examined during the period from 1986 to 1993. Eight sera of 675 were antibody positive in an indirect fluorescent antibody test. Antibody positive rats were found in 1988, 1990, 1991 and 1992 and the numbers of rats were 1, 1, 3 and 3, respectively. A hantavirus strain was isolated from a rat captured in 1990 at a residential area adjoining to a pier in Nagoya port. The virus strain, named NR-9, was identified antigenically as the Seoul type of hantavirus in a neutralization test. Suckling rats inoculated with NR-9 strain survived, while those with SR-11 strain succumbed. A difference between the virulence of strains, NR-9 and SR-11 was demonstrated.

Animals↗

Testicular spermatid and epididymal sperm head counts as an indicator for reproductive toxicity in rats.

The testes of rats were exposed to a single soft x-ray irradiation at levels of 10, 25 and 63 Gy. Testicular and cauda epididymal weights and their sperm counts were decreased at 7 weeks after the irradiation. Histologically, there was an evidence of interrupted spermatogenesis dose-dependently. Animal mating trails, in which irradiated males were mated with untreated females revealed a slight increase in early stage of postimplantation loss at as low as 10 Gy. There were increases in preimplantation and early stage of postimplantation losses in the group of irradiated at 25 Gy. Infertility occurred in irradiated males at 63 Gy. The effects of irradiation were more severe on the sperm count parameters than on reproductive organ weights, histological examination and reproductive status. The testicular spermatid and epididymal sperm head counts are considered to be useful indicators to detect quantitatively the adverse effects on spermatogenesis.

Animals↗