Biomedical subjects
Publications and source records attributed to T Aoki.
A 15-month-old female infant with nystagmus, gait disturbance, diminished reflexes, ophthalmoplegia, and facial paresis was diagnosed as having Fisher syndrome. Magnetic resonance imaging revealed a transient, high-signal-intensity lesion on the left side of the cerebellum on T2-weighted images. The ataxia of Fisher syndrome is not compatible with polyneuritis, but can be explained by a cerebellar lesion, as seen in this case.
To clarify the factors influencing the concentrations and distribution of metal elements in the lung, we analyzed the following 8 metals in the 5 lung lobes of 17 autopsied urban dwellers by flame or flameless atomic absorption spectrometry: aluminum (Al), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb), manganese (Mn), copper (Cu), and Zinc (Zn). The arithmetic mean value (in micrograms of metal per gram of dry weight) calculated for five lobar metal concentrations in each subject ranged from 80 to 681 for Al, from 0.34 to 3.41 for Cd, from 0.41 to 12.7 for Cr, from 0.22 to 1.93 for Ni, from 0.15 to 1.47 for Pb, from 0.64 to 2.36 for Mn, from 2.84 to 7.24 for Cu, and from 40.7 to 77.6 for Zn. The eight metals were classifiable into two groups on the basis of the interindividual and interlobar concentration variations. The first group, consisting of Cu and Zn, was characterized by smaller interindividual variations (co-efficient of variation, CV < 30%) and smaller inter lobar variations (mean CV < 15%). Their levels were not affected significantly by sex, smoking habits, or possible occupational exposure to metal-containing dust. In contrast, the second group, consisting of Al, Cd, Cr, Ni, Pb, and Mn, exhibited larger interindividual variations (CV > 45%) and larger interlobar variations (mean CV > 25%). Concentrations of these metals, except for Cd, tended to be higher in the upper lobes than in the lower lobes. The concentrations of Al and Cr were significantly higher in men than in women. Smoking significantly elevated the levels of Cr, Cd, Ni, and Pb, and the concentrations of Al, Cr, Ni, and Mn were higher in subjects with possible occupational exposure to metal-containing dust than in those without such exposure. However, the interlobar distribution patterns of the metals did not seem to be influenced by sex, smoking habits, or occupational exposure to metal-containing dust.
Striated rootlets in ciliated cells are conical banded structures composed of longitudinally aligned filaments. The formation of striated rootlets during ciliognesis in the human oviduct epithelium was studied by electron microscopy. Primitive rootlets appeared at the proximal side of basal bodies before or at the same time as ciliary budding. After the formation of several striations, the tip of the rootlets extended deeply toward the interior of the cell and became differentiated into two distinct parts, viz., the proximal conical part connected to the basal body and the distal fibrillar part. The periodicity of the striations in the fibrillar part was 68. 5+/-2.95 nm, about 5 nm longer than that of the conical part (63. 9+/-2.25 nm). The dark band in the striation was thicker in the fibrillar part than in the conical part. Since the fibrillar part was not observed in the mature cilium, this part was considered as being either degraded or changed into the conical part during ciliogenesis.
The molecular structure of the biologically active diterpene alcohol isolated previously from the root-stalks of Dicranopteris pedata and Gleichenia japonica was confirmed to be (6S,13S)-cleroda-3,14-diene-6,13-diol by an X-ray crystallographic analysis, together with application of the octant rule to the Cotton effect observed in the CD spectrum of its 6-keto derivative. Further investigation of the root-stalks of D. pedata has resulted in the isolated two new glycosides, which were characterised as (6S,13S)-6-O-[beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl] 13-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-fucopyranosyl] cleroda-3,14-diene and (6S,13S)-6-O-[beta-glucopyranosyl]-13-O-[beta-fucopyranosyl-(1-->2) -alpha-rhamnopyranosyl]-cleroda-3,14-diene. Of these two glycosides, the former glycoside accelerated the growth of the stems of lettuce and inhibited the growth of the roots.
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The present study examined an 11-year-old girl with Down syndrome who suffered from acute myeloblastic leukemia (AML) preceded by preleukemic pancytopenia. Chromosomal analysis of leukemic cells revealed a chromosome change at t(8;21) and trisomy 8 associated with constitutional trisomy 21. Treatment with antineoplastic agents led to complete remission.
Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injected at a suprapharmacologic dose (100 microg/kg) daily for 5 d in normal rats caused marked increases in marrow megakaryocytes and platelet counts at 6-8 d followed by gradual decreases to control levels at 10-20 d. Interestingly, in addition to the expected thrombopoiesis, PEG-rHuMGDF was associated with myelofibrosis with a predominance of reticulin fibres at day 10 followed by complete normalization by day 20. At 6-8 d, the levels of transforming growth factor-beta1 (TGF-beta1) in the extracellular fluid of the marrow, the platelet poor plasma, and the platelet extract were increased 23-, 7- and 2-fold, respectively. The elevated levels of TGF-beta1 were gradually reduced to baseline levels at 13-20 d in accordance with the normalization of myelofibrosis and thrombopoiesis. An ultrastructural analysis showed that large fragments of megakaryocytes were deposited in the marrow parenchyma of PEG-rHuMGDF-treated rats at day 6. PEG-rHuMGDF administration at pharmacologic doses (1 and 10 microg/kg) did not induce the deposition of reticulin fibres in the marrow. These findings suggest that TGF-beta1 leaked from megakaryocytes is involved in the development of the PEG-rHuMGDF-induced myelofibrosis and that this is a reversible process related to the regulation of the excess production of platelets.
AIMS: Recurrence of desmoid tumours is difficult to predict from only histological findings. In this study, immunohistochemistry for counting stromal blood vessels and proliferative activity, DNA flow cytometry, and interphase cytogenetic analysis of chromosome 8 by fluorescence in-situ hybridization (FISH) were performed to assess the correlation between their parameters and the recurrence of desmoid tumours. METHODS AND RESULTS: The cases examined included 16 extra-abdominal desmoid and eight abdominal desmoids, comprising 14 recurrent and 10 non-recurrent cases. Eleven (69%) of the 16 extra-abdominal desmoids and three (38%) of the eight abdominal desmoids recurred. Patients with recurrent lesions (mean age, 20 years) were younger than those with non-recurrent tumours (34 years). Histologically, tumours with hypervascular areas frequently recurred after surgery in comparison with those with hypovascularity. There was no significant correlation between tumour size, the labelling index of the proliferating cell nuclear antigen (PCNA) and the recurrence. In flow cytometric analysis, all the cases examined showed a diploid pattern. The FISH study revealed that the incidence of trisomy 8 was significantly higher in the recurrent (72.7%) than in the non-recurrent cases (12.5%). CONCLUSIONS: These results suggest that a subgroup of desmoid tumours at risk of recurrence may be hypervascular lesions associated with trisomy 8.
We have cloned and sequenced the haemolysin gene locus from Edwardsiella tarda (ETH). This region encoded two open reading frames, designated ethA and ethB. ethA is the haemolysin gene consisting of 4782bp encoding a product of 165.3 kDa and ethB is an activation/secretion protein gene of 1677bp that encodes a product of 61.9 kDa. There were two putative ferric uptake regulator (Fur) binding sites on the 5' upstream region of the ethB gene overlapping the promoter region and ribosome-binding site. The haemolysin produced by the cloned gene was secreted by Escherichia coli. The deduced amino acid sequences of the ethA and ethB genes were found to be homologous to those of the haemolysin and activation/secretion proteins of Haemophilus ducreyi, Proteus mirabilis, and Serratia marcescens. E. coli carrying the ethA gene but not the ethB gene completely lost haemolytic activity, although the ethA gene was transcribed. The protein expressed by E. coli carrying a recombinant plasmid which encoded the ethA gene had haemagglutination activity. The EthB protein was necessary for activation of EthA protein (haemolysin). The ethA and ethB genes were very prevalent in haemolytic E. tarda strains isolated from diseased fish. Transcription of the ethB gene was regulated by iron. The ethA and ethB genes were transcribed independently.
In the human oviduct epithelium during ciliogenesis, short tubular structures were found in the transitional zone between the basal body and cilium. The tubules, termed transitional tubules from their location, were 34-36 nm in diameter and 0.13 +/- 0.06 micron in length; the number around a basal body was variable, but usually 4-6. The cytoplasmic leaflets of the tubule membranes were coated by electron-dense material and appeared to be connected to alar sheets. The transitional tubules existed transiently during ciliogenesis. The exact role of transitional tubules is unknown, but considering their location, they may fix the basal body in the apical cytoplasm during ciliary elongation and/or may be related to formation of alar sheets.
A fusion protein between green fluorescent protein (GFP) and neuron-specific enolase (NSE) was expressed in Escherichia coli. The GFP-NSE fusion protein migrated at 62 kDa in SDS-PAGE and retained the fluorescence under non-heating conditions. However, heat-denatured GFP-NSE was non-fluorescent and migrated at 74 kDa corresponding to the theoretical value. This suggests that the special structure of GFP, which is not denatured by SDS, influences its mobility in SDS-PAGE under non-heating conditions. The fluorescence intensity of GFP-NSE was measurable over a wide range by spectrophotometry or densitometry. The competitive immunoassay for NSE was performed using GFP-NSE as labeled antigen. Under our assay conditions, the working range of this system was about 2 -60 ng. This simple and rapid fluorescence immunoassay (FIA) using GFP-tagged antigen may be applicable to many protein markers.
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We have found that expression of the Bip (immunoglobulin heavy chain binding protein)/GRP78 (glucose regulated protein 78) gene is markedly enhanced specifically among the heat shock protein (HSP) 70 gene family during the neuronal cell death of PC12 (22a) cells, that is induced by removal of nerve growth factor (NGF) and blocked by a transcription inhibitor, actinomycin D. The Bip mRNA induction is suppressed when the NGF-deprivation-dependent cell death of PC12 (22a) cells is inhibited by cAMP, cycloheximide or high K+. The Ca2+ ionophore, A23187, caused neuronal cell death accompanied by up-regulation of Bip, HSP90, and HSP70 mRNAs. In addition, a chelator of intracellular Ca2+ (BAPTA) elevated Bip mRNA and induced cell death in a low Ca2+ medium. Alterations of intracellular calcium homeostasis thus appear to induce Bip mRNA expression as well as apoptosis in PC12 (22a) cells. However, release of Ca2+ from intracellular stores by thapsigargin induced Bip mRNA expression but not cell death, indicating that Bip mRNA induction is not sufficient for neuronal death. Induction of Bip mRNA in association with apoptosis was also observed for NGF-deprived sympathetic ganglion cells in primary culture. These lines of evidence suggest that selective induction of Bip mRNA may play an important role in the programmed cell death of neurons deprived of neurotrophic factors and could be a landmark of the neuronal programmed cell death.
We demonstrated the inhibitory effect of halothane (HAL) inhalation on the metabolism of chlorzoxazone (CZZ), a substrate for CYP2E1, in a bolus and a continuous injection study in rabbits receiving artificial ventilation. In a bolus injection study, the inhalation of 1.0% HAL significantly increased the half-life and the area under the curve and decreased the clearance of CZZ compared with those variables in midazolam administration. In a continuous injection study, the effect of various concentrations of inhaled HAL on plasma CZZ concentration at steady state was compared. Systolic and diastolic arterial blood pressure were decreased dose-dependently after 0.5%, 1.0%, or 2.0% HAL was inhaled. Although the plasma concentration of CZZ was increased 2.5-fold after 3 h of HAL inhalation, there was no significant difference in mean plasma concentrations among the groups treated with 0.5%, 1.0%, or 2.0% HAL. In contrast, the plasma concentration of lidocaine, a substrate for CYP3A, remained unchanged after 1.0% HAL was inhaled. These results suggest that general anesthesia obtained with HAL inhalation will affect the metabolism of drugs administered concomitantly when the drug is a substrate for CYP2E1.
Recent investigations have been suggesting that some neuronal subpopulations may die via programmed cell death after focal ischemic injury. To clarify the possible roles of the genes involved in the cell-death program, this study examined the expression of three members of the interleukin-1 beta converting enzyme (Ice) gene family (Ice, Nedd2, and Yama/CPP32) and two members of the bcl-2 gene family (bcl-2 and bcl-x) in the rat brain after permanent occlusion of the middle cerebral artery. Northern blot analysis revealed a transient induction of Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32 mRNA 16 to 24 h after the insult (5.8-fold at 24 h), whereas the expression of Ice remained constant. The expression of bcl-2 and bcl-x remained constant after the ischemic insult. Taking into account the key role of the Ice gene family in the execution of programmed cell death, the induction of Ice gene family might play a causative role in apoptotic cell death.
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Adhesion molecules play a major role in the processes of invasion and metastasis of malignant tumors. Their expression within tumors has been reported to be quantitatively and qualitatively altered according to the invasiveness and metastatic potential of the tumor. The present study tested whether the intratumoral expression of integrin alpha 3 can be detected by a radiolabeled monoclonal antibody. The in vitro binding study with four different human cancer cells showed that radioiodinated GA17 antibody recognizing integrin alpha 3 bound specifically to these cells to varying degrees, according to the antigen density on each cell. The biodistribution study with 125I- and 111In-labeled antibodies showed specific localization of radiolabeled GA17 to the xenografts. However, the in vivo tumor localization was not proportional to the antigen density calculated in vitro, and antibody metabolism varied among the tumors, as was also confirmed by in vitro radionuclide retention assay. The intratumoral distribution of radioactivities varied reflecting the antigen expression within the tumor. These results indicate that 1) integrin alpha 3 was expressed in various kinds of tumors and could be localized by the radiolabeled antibody, and 2) the expression of integrin alpha 3 and the metabolism of the radiolabeled antibody after binding to the antigen within the tumor were variable among the tumors, which affected the radionuclide distribution characteristics. The expression of adhesion molecules within these tumors was noninvasively detected by a radiolabeled antibody. It may be possible to use integrin alpha 3, when it is overexpressed, as a target of therapy with antibodies radiolabeled with alpha or beta emitters.
The Japanese Society of Gastroenterology (JSGE) will celebrate the centenary of its foundation in 1998. A variety of plans and projects are being prepared by the JSGE centennial celebration committee. In this article, the history of the JSGE is briefly described, and several projects, including the international symposium currently being planned, are introduced. The future prospects of our Society will also be described.