Biomedical subjects
Publications and source records attributed to T Oshima.
The authors describe a simple and available abdominal wall-lift technique for endoscopic surgery that involves a new suction lifter that they designed for laparoscopic surgery. Since July 1998, the authors have used this technique successfully in eight patients with appendicitis, in one patient with a perforated duodenal ulcer, and in one patient with an adenoma of the ascending colon.
Pulmonary functions are classified two kinds of functions which are respiratory and non-respiratory. We explained new clinical significant results by looking at the usual respiratory pulmonary function tests and devices in this paper. We found two new indexes on uneveness of ventilation by analyzed compartments of forced expiratory curves(Tiffneu curves) and at improvement of CO single breathing method on diffusing capacity test. We found new index on bronchial anaphylaxis for bronchial asthma by time constant measured from forced expiratory curves, also. We found new index on ventilatory efficiency at developing the automatic respiratory resistance meter by the forced oscillation method of Du Bois, too.
Mutations in the SOX10 gene, encoding a cell-lineage specific transcription factor, are associated with congenital deafness. We analyzed the expression of Sox10 mRNA in developing mouse inner ear by in situ hybridization. Sox10 mRNA is expressed in the entire epithelia of the otic vesicle at embryonic day 11.5 (E11.5) and in the developing cochlea and vestibule at E13.5. In postnatal day 8 and adult cochleas, Sox10 expression is restricted to the supporting cells of the organ of Corti. These expression profiles suggest that Sox10 is important for development of the cochlea.
Connexin 31 (Cx31) mutations cause an autosomal dominant form of high-frequency hearing loss. The immunohistochemical localization of Cx31 in mouse cochlea was studied at different ages between 0 and 60 days after birth (DAB). Cx31-like immunoreactivity was detected in fibrocytes of spiral ligament and spiral limbus at 12 DAB, gradually enhanced with the increase of age and reached the adult pattern on 60 DAB. Immunoreactivity decreased gradually from the basal to apical turn in all developmental stages. The mRNA of Cx31 was also identified by RT-PCR. The distribution of Cx31 and connexin 26 were obviously different in the developing mouse cochlea. The expression and distribution of Cx31 in the development may explain the progressive hearing loss in human Cx31 mutations.
The photoinduced electron transfer reaction of halogenated 1,4-benzoquinones with 2,3-dimethyl-2-butene or 3,4-dimethyl-2-pentene gave the primary, secondary, and tertiary monoallyl ethers of hydroquinones, with the product distributions highly dependent on the steric nature of quinones and olefins.
A number of proteins are expressed in the organ of Corti and are considered to be responsible for hearing. However, most of them have not been identified. Therefore, to achieve a better understanding of the genetic factors influencing these traits, the first step is to characterize the genes expressed in the organ of Corti. In the present study, a cDNA library was constructed from the guinea pig organ of Corti. After sequencing isolated clones, 196 expressed sequence tags (ESTs) were identified with FASTA analysis: 65 ESTs showed significant sequence homology to previously identified genes in guinea pig, human or other species, and 131 ESTs showed no significant matches to sequences already present in the DNA database DDBJ/GenBank/EMBL. A variety of matching sequences, some of which were known to be cochlea-specific, were found through FASTA analysis of the 65 clones. RT-PCR with a panel of 10 different tissue mRNA revealed the restricted expression of 13 unknown clones. The results of our analysis allowed the establishment of a list of genes expressed in the guinea pig organ of Corti.
Irradiation of various meta- and para-substituted homobenzoquinones with ethyl vinyl ether gave the [2 + 2] photoadducts, tricyclic diones, regio- and endo-selectively and in good yields. The tricyclic skeleton has an anti-form built by the addition of ethyl vinyl ether from the less hindered side of homoquinones. All of the CH(3), Cl, Br, and CH(3)O substituents at the reacting C=C double bond afforded head-to-head (HH) addition predominantly. In the case of CH(3), Cl, and Br, the ethoxy group was oriented in the endo-position, while the CH(3)O substituent led to a 1/5 mixture with the exo-isomer. It was also found that the Br-substituted [2 + 2] adducts undergo a facile skeletal rearrangement, being converted into dihydro-o-benzoquinone monomethide derivatives for para-substitution and dihydrobenzofuran derivatives for meta-substitution, probably under the influence of the in situ generated HBr. Intramolecular [2 + 2] photocycloaddition of an alkenylhomobenzoquinone afforded a tetracyclic dione.
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omega-Agatoxin IVA-sensitive Ca(2+) channels have been thought to be involved in physiological excitatory amino acid glutamate release and these channels may also contribute to the development of ischemic brain injury. Recently, we demonstrated that alpha-eudesmol from Juniperus virginiana Linn. (Cupressaceae) inhibits potently the presynaptic omega-agatoxin IVA-sensitive Ca(2+) channels. In the present study, we investigated the effects of alpha-eudesmol on brain edema formation and infarct size determined after 24 h of reperfusion following 1 h of middle cerebral artery occlusion in rats. We first found that alpha-eudesmol concentration-dependently inhibited glutamate release from rat brain synaptosomes and that its inhibitory effect was Ca(2+)-dependent. In the middle cerebral artery occlusion study, intracerebroventricular (i.c.v.) treatment with alpha-eudesmol significantly attenuated the post-ischemic increase in brain water content. alpha-Eudesmol also significantly reduced the size of the infarct area determined by triphenyltetrazolium chloride staining after 24 h of reperfusion. Using a microdialysis technique, we further demonstrated that alpha-eudesmol inhibits the elevation of the extracellular concentration of glutamate during ischemia. From these results, we suggest that alpha-eudesmol displays an ability to inhibit exocytotic glutamate release and to attenuate post-ischemic brain injury.
OBJECTIVE: HIV-1 infection is associated with alterations of several vascular endothelial functions including adhesion molecule expression, growth, and vascular permeability. The bases of these errors are not known, but might involve secretion of the HIV-1 derived transcription factor 'Tat-1'. This study investigated Tat-1 mediated endothelial barrier changes and second message regulation of this phenomenon. METHODS: We exposed human umbilical vein endothelial cell monolayers to Tat-1 (0-150 ng/ml) for up to 48 h and measured resulting changes in monolayer permeability. We also investigated the role of tyrosine and mitogen activated protein (MAP) kinases, and protein kinase G using the pharmacological blockers genistein, PD98059 and KT5823 respectively. RESULTS: Tat-1 significantly reduced monolayer barrier and increased albumin permeability within 24 h. Tat-1 also stimulated tyrosine phosphorylation of multiple endothelial proteins, disorganized junctional phosphotyrosine staining and increased the number of these immunostaining structures. The increased permeability produced by Tat-1 was blocked by genistein and PD98059, but not by KT5823. Genistein and PD98059 pretreatment also prevented the changes in phosphotyrosine immunostaining produced by Tat-1 and blocked phosphorylation of several proteins including MAP kinase. CONCLUSION: These results suggest that HIV may dysregulate endothelial barrier through the effects of Tat-1. These blocker experiments suggest that the effects of Tat are transcription/translation-dependent. These data demonstrate that Tat increases endothelial albumin permeability in vitro through tyrosine kinase and MAP kinase, but not protein kinase G pathways.
[reaction: see text] Irradiation of homonaphthoquinones with spiro-linked dibenzocycloheptene rings brings about the Norrish type II reaction to give polycyclic alcohols via a stereospecific 1,7-hydrogen abstraction of the less stable twist-boat conformer.
The release of glutamate during brain anoxia or ischaemia triggers the death of neurons, causing mental or physical handicap. The mechanism of glutamate release is controversial, however. Four release mechanisms have been postulated: vesicular release dependent on external calcium or Ca2+ released from intracellular stores; release through swelling-activated anion channels; an indomethacin-sensitive process in astrocytes; and reversed operation of glutamate transporters. Here we have mimicked severe ischaemia in hippocampal slices and monitored glutamate release as a receptor-gated current in the CA1 pyramidal cells that are killed preferentially in ischaemic hippocampus. Using blockers of the different release mechanisms, we demonstrate that glutamate release is largely by reversed operation of neuronal glutamate transporters, and that it plays a key role in generating the anoxic depolarization that abolishes information processing in the central nervous system a few minutes after the start of ischaemia. A mathematical model incorporating K+ channels, reversible uptake carriers and NMDA (N-methyl-D-aspartate) receptor channels reproduces the main features of the response to ischaemia. Thus, transporter-mediated glutamate homeostasis fails dramatically in ischaemia: instead of removing extracellular glutamate to protect neurons, transporters release glutamate, triggering neuronal death.
Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction protein and is expressed in the inner ear, have been shown to be responsible for a major part of nonsyndromic hereditary prelingual (early-childhood) deafness in Caucasians. We have sequenced the GJB2 gene in 39 Japanese patients with prelingual deafness (group 1), 39 Japanese patients with postlingual progressive sensorineural hearing loss (group 2), and 63 Japanese individuals with normal hearing (group 3). Three novel mutations were identified in group 1: a single nucleotide deletion (235delC), a 16-bp deletion (176-191 del (16)), and a nonsense mutation (Y136X) in five unrelated patients. The 235delC mutation was most frequently observed, accounting for seven alleles in 10 mutant alleles. Screening of 203 unrelated normal individuals for the three mutations indicated that the carrier frequency of the 235delC mutation was 2/203 in the Japanese population. No mutation was found in group-2 patients. We also identified two novel polymorphisms (E114G and I203T) as well as two previously reported polymorphisms (V27I andV37I). Genotyping with these four polymorphisms allowed normal Japanese alleles to be classified into seven haplotypes. All 235delC mutant alleles identified in four patients resided only on haplotype type 1. These findings indicate that GJB2 mutations are also responsible for prelingual deafness in Japan.
A complement regulatory protein, decay-accelerating factor (DAF, CD55), is known to protect host tissues from autologous complement activation. DAF is present on the apical side of human gastric epithelial cells, and its expression increases during gastritis. To develop an animal model for analysis of DAF expression on gastric cells, a mAb to guinea pig DAF was successfully used. Although DAF expression in the mucosal epithelium of the stomach is weak, as judged by immunohistochemical staining with the mAb, it was temporarily up-regulated at 12 and 24 h, and at 3 days after ischemia reperfusion (I/R) (p < 0.05). The DAF mRNA level in gastric tissues was determined by Northern blot analysis and found to be highest at 6 h after I/R, returning to the baseline at 24 h. Strong DAF mRNA expression was observed in the cytoplasm of cells beneath the eroded tissues 6 h after I/R. In guinea pigs, alternative splicing of DAF mRNA generates both GPI-anchored types and transmembrane types of DAF. RT-PCR analysis revealed that mRNAs of the transmembrane types had become significantly dominant by 6 h after I/R, whereas levels for the GPI-anchored types remained unchanged. In guinea pigs depleted of complement by cobra venom factor treatment, the area of erosion and the up-regulation of DAF expression in gastric epithelial cells after I/R were significantly limited compared with the normocomplementemic group, indicating that DAF may be up-regulated by an inflammatory stress.
To verify the role of macrophage migration inhibitory factor (MIF) in tumourigenesis, we examined the effect of an anti-MIF antibody on tumour growth and angiogenesis. We inoculated murine colon adenocarcinoma cell line colon 26 cells subcutaneously into the flank in BALB/c mice. After nine days, we treated tumour-bearing mice with an anti-rat MIF antibody by intraperitoneal injection on days 9, 11, 13, 15, 17, 19 and 21. We found significant inhibition of tumour growth by this treatment from day 15 to day 22. Next, we implanted a chamber filled with colon 26 cells, which only passes soluble factors, in the subcutaneous fascia of the flank, and treated mice with the anti-rat MIF antibody at days 1, 3 and 5. By histological examination at day 6, angiogenesis within the subcutaneous fascia in contact with the chamber was markedly suppressed. In vitro, we added an anti-human MIF antibody to human umbilical vein endothelial cells (HUVEC) to evaluate its effect on cell growth by measurement of [3H]thymidine incorporation. We observed that the anti-MIF antibody significantly suppressed [3H]thymidine uptake by HUVEC. These results suggest the possibility that MIF is involved in tumourigenesis via promotion of angiogenesis.
PURPOSE: To determine how anterior advancement of the mandible (ADM) affects spontaneous breathing through the nasal route in healthy human volunteers sedated with intravenous midazolam. METHODS: In four subjects who exhibited nasal breathing during midazolam sedation (intravenous dose: 0.09+/-0.02 mg x kg(-1), mean +/- SD), we measured respiratory rate (RR), peak nasal inspiratory airflow rate (V(nIpeak)) peak nasal expiratory airflow rate (V(nEpeak), duty ratio (Ti/Ttot) and nasal resistance (Rn) before and after ADM. Nasal resistance was calculated by dividing the difference between nasal mask and oropharyngeal pressure by airflow rate at peak nasal inspiratory airflow. RESULTS: The RR, V(nIpeak), and V(nEpeak) increased following ADM (P<0.001, respectively). On the contrary, Ti/Ttot decreased after ADM (P<0.001). Consequently, ADM decreased Rn from 30.4+/-40.8 to 5.0+/-5.6 (cm H2O x l(-1) x sec(-1)) (mean +/- SD) (P<0.001). In these four subjects, no respiratory airflow was observed through the oral route before and after ADM. CONCLUSION: Advancement of the mandible decreases nasal resistance, thereby facilitating spontaneous breathing through the nasal route in normal humans sedated with midazolam.
PURPOSE: To evaluate the effects of midazolam sedation followed by flumazenil antagonism on the work of nasal breathing in normal humans. METHODS: We measured minute ventilation through the nasal route, respiratory frequency, nasal resistance (Rn) and the work of nasal breathing under three conditions: awake, during midazolam sedation, and after flumazenil antagonism in eight healthy human subjects. A custom-made, partitioned face mask enabled nasal and oral airflow to be measured separately. To calculate Rn and the work of nasal breathing, nasal mask and oropharyngeal pressure was also measured. RESULTS: Total resistive work spent on the upstream segment of the nasal route per minute (Wn) (J x min(-1)) was greater during midazolam sedation (3.6 +/- 2.9) than while awake (1.6 +/- 0.9) and after flumazenil antagonism (1.7 +/- 0.6), respectively (mean +/- SD) (P < 0.05). Total resistive work spent on the upstream segment of nasal breathing (WnNnE) (JxL(-1)) increased from 0.31 +/- 0.14 to 0.75 +/- 0.61 after midazolam administration (P < 0.05) and decreased to 0.31 +/- 0.10 after flumazenil. Following midazolam administration, a strong correlation was observed between changes in WnNnE and changes in Rn r = 0.852, P < 0.0001), whereas there was no correlation between changes in Wn and changes in Rn r = 0.159, P = 0.279). CONCLUSION: The work of breathing spent on the upstream segment of the nasal route increases during midazolam sedation and returns to baseline after flumazenil antagonism.
Restriction fragment length polymorphisms of the vitamin D receptor gene have recently been reported to be associated with changes in bone mineral density. Alterations in systemic calcium balance and Ca-regulating hormones such as 1,25(OH)2 vitamin D3 and parathyroid hormone have been demonstrated in essential hypertension. We investigated the relationship between polymorphisms of the vitamin D receptor gene and systemic Ca metabolism in patients with essential hypertension and in normotensives. We compared 147 subjects with essential hypertension and 100 normotensive control subjects. The genotype distribution and derived allele frequencies for the vitamin D receptor gene were similar in the two groups (genotype bb/Bb/BB and allele B/b: 60.1/32.6/7.2 and 0.24/0.76 in hypertensives vs. 56.0/36.0/8.0 and 0.26/0.74 in normotensive subjects). Serum concentrations of total Ca in the bb, Bb, and BB groups were, respectively, 4.5+/-0.3 vs. 4.5+/-0.4 vs. 4.4+/-0.5 mmol/l in normotensives and 4.6+/-0.3 vs. 4.6+/-0.4 vs. 4.4+/-0.5 mmol/l in hypertensives. Ionized Ca levels were 1.17+/-0.04 vs. 1.16+/-0.04 vs. 1.15+/-0.04 mmol/l in normotensives and 1.16+/-0.04 vs. 1.16+/-0.04 vs. 1.14+/-0.05 mmol/l in hypertensives, respectively. These results indicate that the BB genotype of the vitamin D receptor gene is associated with lower serum Ca levels but is not a useful predictive marker for the development of essential hypertension in Japanese subjects.