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Biomedical subjects

E Fujita

Publications and source records attributed to E Fujita.

At least 37 records · Page 2Linked to original sources
PubMed1999

BMP-4 and retinoic acid synergistically induce activation of caspase-9 and cause apoptosis of P19 embryonal carcinoma cells cultured as a monolayer.

In monolayer cultures of P19 EC cells treated with both all-trans retinoic acid (RA) and bone morphogenetic protein (BMP)-4 (RA/BMP-4 treatment), many non-adherent apoptotic cells and activated caspase-3-positive cells were observed, but they were not observed in cells treated with RA or BMP-4 alone. Consistent with the appearance of activated caspase-3-positive cells, BMP-4 and RA together induced processing of caspase-9, Ac-DEVD-MCA cleavage activity and DNA fragmentation. These three activities were observed infrequently or not at all when cells were treated with RA or BMP-4 alone. In the RA/BMP-4 treatment-induced apoptosis, caspase-9 was upstream of caspase-3 in the enzyme cascade, and the caspase-9 to -3 step was key in the apoptotic pathway. Bcl-xL inhibited processing of caspase-9, Ac-DEVD-MCA cleavage activity and DNA fragmentation induced by RA/BMP-4 treatment. However, unlike staurosporine-induced apoptosis, cytochrome c, which activates caspase-9, was not detected in the cytosol of RA/BMP-4-treated cells. RA and BMP-4 may activate caspase-9 through an apoptotic pathway other than the Apaf-1/cytochrome c pathway. The prominent decrease of X-chromosome-linked inhibitory apoptosis protein (XIAP) in the cytosol may explain the activation of caspase-9 induced by RA and BMP-4 treatment.

Animals↗
PubMed1999

Effect of mandibular advancement splint on psycho-intellectual derangements in patients with sleep apnea syndrome.

The mandibular advancement splint (MAS) was recently introduced for the management of sleep apnea syndrome (SAS), although its effects on psycho-intellectual functions have not been elucidated yet. We examined psycho-intellectual function before and after treatment with MAS in patients with SAS. Twenty patients with SAS underwent psycho-intellectual function testing before and after treatment with MAS for 3 to 4 weeks. The apnea index significantly decreased from 19.0+/-15.6 to 2.4+/-1.9. The state anxiety score significantly decreased from 44.6+/-12.1 to 33.7+/-11.1, the trait anxiety score significantly decreased from 46.2+/-13.4 to 37.6+/-13.8, and the depression scale score significantly decreased from 39.2+/-11.0 to 30.8+/-9.9 with MAS treatment. By the Cornell Medical Index and the Yatabe-Guilford test, the patients became less neurotic and less eccentric after treatment. By the Uchida-Kraepelin psychodiagnostic test, calculation ability significantly increased from 1247.4+/-402.1 to 1950.2+/-651.9. We conclude that MAS treatment reduces apneic episodes and improves psycho-intellectual derangements in patients with SAS.

Adult↗
PubMed1999

[Long-term follow-up study on sequelae of carbon monoxide poisoning; serial investigation 33 years after poisoning].

1. We examined 156 patients 33 years after CO poisoning occurred at the Miike Mikawa Mine, Fukuoka, Japan. The subjects were classified according to age as follows: between 55 and 59 years (n = 14), 60 and 69 years (n = 62), 70 and 79 years (n = 60), and 80 and 87 years (n = 18). The mean age was 69.2 years old. Concerning the duration of coma that occurred soon after the accident, 64 remained comatose from 0 to 6 hours, 46 from 6 to 12 hours and 46 from 12 to 48 hours. 2. Subjective symptoms were observed in 96.8% of the patients. Among them, forgetfulness was noted in 89.7%, followed by irritability in 66.7%, headache in 59.6%, insomnia in 55.8%, limb pain in 46.8%, dull head feeling in 42.9% and dizziness in 36.5%. 3. Intellectual disturbances were observed in 68.6% of the patients, including impression disturbance in 58.3%, memory disturbance in 51.9%, calculation disturbance in 63.5%, thinking disturbance in 61.5% and disorientation in 14.1%. 4. Apathy and disorder of volition and interest which were found in 72.4% were included in personality change because all symptoms persisted for many years. Personality change was classified as follows: weakness of emotion and will (hypobulia) in 54.4%, infantilism in 35.2%, hyperactive, talkactive and lack of inhibition in 18.5%, lack of self-possession and unstable temper in 9.6%, depression in 15.3%, neurosis in 7.6% and schizophrenic state in 2.5%. Among these symptoms of personality change, weakness of emotion and will and infantilism were conspicuous among the patients who remained in a coma for more than 6 hours soon after the accident but showed no relationship with age. 5. Neurological symptoms that were found in 48.7% of the patients were classified as sensory disturbance in 25.6%, peripheral nerve symptoms in 16.0%, pyramidal symptoms in 14.1%, ataxia and cranial nerve symptoms in 7.1%, paroxysmal symptoms in 6.4% and focal symptoms in 4.5%, extrapyramidal symptoms in 21.8% (Parkinsonism in 4.5%, tremor in 10.9% and muscle rigidity in 16.0%) and vegetative symptoms in 37.2%. 6. At the time of investigation, 5 CO poisoning patients were classified as serious cases (3.2%), 20 as comparatively serious (12.8%) medium-degree cases, 28 as comparatively mild (17.9%) medium-degree cases, 37 as comparatively serious (23.7%) mild cases, 42 as comparatively mild (26.9%) mild cases, 24 (15.4%) as having symptoms which were not problematic, and 24 (15.4%) as having symptoms that markedly worsened due to complication. 7. A total of 138 (88.4%) cases had complications were classified as follows: 78 cases (50.0%) of hypertension, 62 cases (39.7%) of cerebral infarction, 24 cases (15.4%) of cardiac disturbance, 21 cases (13.5%) of diabetes mellitus, 14 cases (9.0%) of hepatic disturbance and six cases of silicosis (3.8%). 8. Cranial MRI was carried out for 129 cases (82.7%). Of the abnormal findings identified, cerebral atrophy accounted for 72.0% (93 cases), including moderate and severe cases in 47.2% (61 cases), pallidum lesion for 37.9% (49 cases), lacunar infarction (including cerebral infarction) for 52.7% (68 cases), and hippocampal atrophy for 18.6% (24 cases). Many cases of cerebral atrophy and hippocampal atrophy were observed in patients who remained in the initial coma for more than 12 hours and were 80 years of age or old. The cases of pallidum lesion were observed in patients who remained in the initial coma for more than 6 hours, and no relationship with age was found. The other findings, cerebral atrophy and lacunar infarction showed a slight relationship with age. 9. Among the moderate and serious cases of intellectual disturbance, cerebral atrophy constituted to 62.5%, lacunar infarction 68.7% and pallidum lesion 50.0%. Among the moderate and serious cases of personality change, cerebral atrophy constituted 78.5%, lacunar infarction 35.0% and pallidum lesion 50.0%. Moreover, among extrapyramidal symptoms, pallidum lesion constituted 58.6%, cerebral atrophy 55.1% and lacun

Accidents, Occupational↗
PubMed1998

RA70 is a src kinase-associated protein expressed ubiquitously.

RA70, which is expressed during neuronal differentiation of P19 EC, is highly homologous to human src kinase-associated phosphoprotein (SKAP55). Here we isolated human full-length RA70 cDNA. Unlike SKAP55, which is specifically expressed in thymus and T cells, RA70 was expressed ubiquitously in various tissues including lung, skeletal muscle, and spleen, and in various cell lines including human monocytic leukemia (U937) cells, but RA70 was undetectable in thymus and T cell lymphoma (Jurkat) cells. RA70 as well as SKAP55 proved to be a protein with molecular weight 55 kDa associated with SH2 domain of Fyn. Interaction between RA70 and src family kinases, Fyn, Hck and Lyn, was detected during monocytes/macrophage-differentiation of U937 cells. Thus, like SKAP55, RA70 is an adaptor protein of the src family kinases. RA70 may play an essential role in the src signaling pathway in various cells.

Amino Acid Sequence↗
PubMed1998

Detection of activated caspase-3 (CPP32) in the vertebrate nervous system during development by a cleavage site-directed antiserum.

We previously demonstrated that Caspase-3 is highly expressed in dorsal root ganglia and trigeminal ganglia of mouse embryos [T. Mukasa, K. Urase, Y.M. Momoi, I. Kimura, T. Momoi, Specific expression of CPP32 in sensory neurons of mouse embryos and activation of CPP32 in the apoptosis induced by a withdrawal of NGF, Biochem. Biophys. Res. Commun., 231 (1997) 770-774.]. Since, however, Caspases are processed into active form during apoptosis, it is difficult to examine the involvement of activated Caspases in naturally occurring cell death during development by immunohistochemical staining or in situ hybridization method. We prepared a cleavage site-directed antiserum against Caspase-3 (anti-p20/17). This antiserum reacted with fragment (p20/17) of Caspase-3, but not proCaspase-3 (p32), proCaspase-7 (p34) and its cleaved fragment (p24). We examined the relationship between the activation of Caspase-3 and the appearance of the naturally occurring apoptotic cells in the nervous system during development. In the trigeminal ganglia and dorsal root ganglia, the expression of Caspase-3 mRNA was maximal before the appearance of p20/17-positive cells and apoptotic cells. In the mouse brain, many p20/17-positive cells and apoptotic cells were observed in the neuroepithelium in the early developmental stages, but very few p20/17-positive cells were detected in postmitotic neurons in the cerebral cortex although Caspase-3 mRNA was expressed highly. Caspase-3 is activated mainly during apoptosis of neuroepithelial cells in the early developmental stages but not of mature neurons at postnatal stages.

Animals↗
PubMed1998

Detection of activated Caspase-3 by a cleavage site-directed antiserum during naturally occurring DRG neurons apoptosis.

We prepared a cleavage site-directed antiserum against Caspase-3 (anti-p20/17), which reacts with the p20/17 fragment (p20/17) activated by cleavage but not proCaspase-3 (p32), and examined the relationship between the activation of Caspase-3 and apoptosis. We identified p20/17-positive cells where cell death occurs naturally: interdigits of the forelimbs, small intestine epithelium, thymus, trigeminal ganglia, and dorsal root ganglia of mouse embryos. Withdrawal of nerve growth factor induced the appearance of p20/17-positive cells with DNA fragmentation in the culture of dorsal root ganglia neurons, while DNA fragmentation was detected in both p20/17-positive and -negative neurons in dorsal root ganglia of mouse embryos. These results suggest that not only activation of Caspase-3 but also other molecular mechanism play a role in the naturally occurring dorsal root ganglia apoptosis. Cleavage site-directed antisera against Caspases will be useful for the analysis of the molecular mechanism of naturally occurring apoptosis during development.

Animals↗
PubMed1998

Free D- and L-amino acids in ventricular cerebrospinal fluid from Alzheimer and normal subjects.

Free D-Ser, D-Asp and total D-amino acids were significantly higher (p < 0.05) in Alzheimer (AD) ventricular CSF than in normal CSF. There was no significant difference in the total L-amino acids between AD and normal CSF, but L-Gln and L-His were significantly higher (p < 0.05) in AD-CSF. The higher concentrations of these D- and L-amino acids in AD ventricular CSF could reflect the degenerative process that occurs in Alzheimer's brain since ventricular CSF is the repository of amino acids from the brain.

Alzheimer Disease↗
PubMed1998

Wortmannin enhances activation of CPP32 (Caspase-3) induced by TNF or anti-Fas.

CPP32/apopain (Caspase-3), a protease of the Ced-3/ICE family, is a central mediator in the apoptosis induced by TNF or anti-Fas. In this study we demonstrate that wortmannin, an inhibitor of PI-3K, enhances the activation of CPP32 (Caspase-3) and DNA fragmentation in TNF-treated U937 cells and anti-Fas-treated Jurkat cells. Caspase-3-like activity, Ac-DEVD-MCA cleavage activity, is enhanced by wortmannin in the range of the concentration (1 - 100 nM) specifically inhibiting PI-3K. LY294002, another PI-3K inhibitor, also enhances Caspase-3-like activity, but inhibitors for myosin light chain kinase and calmodulin dependent kinase do not have any effect on the Caspase-3-like activity. Wortmannin (1 - 100 nM) enhances the processing of Caspase-3 (32K) into active form (17K) in TNF- or anti-Fas-treated cells, but not in untreated cells. These observations suggest that inhibition of PI-3K induces the activation of processing enzyme of Caspase-3 or increases the susceptibility of Caspase-3 to the processing enzyme. PI-3K seems to protect the cells from apoptosis by suppressing the activation of Caspase-3.

Androstadienes↗
PubMed1998

Arizona hazardous air pollutants monitoring program

In order to evaluate the existing risk to public health in Arizona related to hazardous air pollution, ambient air monitoring for selected hazardous air pollutants (HAPs) was carried out in 1994-1996 in several representative urban and rural areas of Arizona. A wide range of organic HAPs was monitored, requiring a variety of sampling and analysis methods. Stainless steel SUMMA canisters were used for collection of volatile hydrocarbons and halocarbons, which were analyzed by capillary gas chromatography with flame ionization and electron capture detection (GC-FID/ECD). Carbonyl compounds were collected using 2,4-dinitrophenylhydrazine-impregnated cartridges and analyzed by high performance liquid chromatography with ultraviolet detection. Semi-volatile and non-volatile polycyclic aromatic compounds were collected using a sampling train consisting of a filter followed by a PUF/XAD-4/PUF sandwich cartridge. Following extraction, samples were analyzed by capillary GC with mass spectrometric detection (GC-MS). Database software was developed for data processing and reporting functions. This paper describes the sampling strategy and the sampling and analysis methods employed in the monitoring program and presents a summary of all the results obtained during the duration of the sampling program.

Journal Article↗
PubMed1997

Involvement of Sonic hedgehog in the cell growth of LK-2 cells, human lung squamous carcinoma cells.

Mutation of the Patched gene has been detected in human inherited basal cell nevus syndrome (BCNS) and sporadic basal cell carcinomas (BCC), suggesting a strong relation between a Sonic hedgehog-Patched signal and cell proliferation. In the present study, we demonstrate that Sonic hedgehog is expressed in human lung squamous carcinoma (LK-2 and EBC-1) and some adenocarcinoma cell lines. The expression of Sonic hedgehog is also detected in the human lung squamous carcinoma tissues, but not in the normal lung tissue of the same patient. The N-terminal region of Sonic hedgehog stimulates the incorporation of BrdU into LK-2 cells and stimulates their cell growth, while anti-Shh-N inhibits their cell growth. These results suggest that a Sonic hedgehog signal is involved in the cell growth of LK-2 cells.

Amino Acid Sequence↗
PubMed1997

High performance polymer supports for enzyme-assisted synthesis of glycoconjugates.

Efficient and practical methodology for the construction of carbohydrates, including oligosaccharide derivatives and sphingoglycolipids, was established on the basis of a water-soluble polymer supports having unique linkers that can be cleaved by specific conditions. Novel glycomonomers for the construction of polymer supports were synthesized and copolymerized with acrylamide to give three types of water-soluble glycopolymers having primer sugars through the specific linkers containing (i) p-substituted benzyl group, (ii) L-phenylalanine residue, and (iii) ceramide-mimetic L-serine derivative, respectively. These glycopolymers were employed for sugar elongation reactions with glycosyl transferases such as GlcNAc beta 1,4-galactosyl transferase, beta Gall-->3/4GlcNAc alpha-2,6-sialyl transferase, and beta Gall-->3/4GlcNAc alpha-2,3-sialyl transferase in the presence of each sugar nucleotide as glycosyl donor to afford polymers having N-acetyllactosamine, sialyl alpha-(2-->6) N-acetyllactosamine, and sialyl alpha-(2-->3) lactose residues in excellent yield. Subsequent hydrogenolysis, hydrolysis with alpha-chymotrypsin, or transglycosylation to ceramide with ceramide glycanase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl alpha-(2-->6) N-acetyllactosamine derivative having a terminal amino group, and ganglioside GM3 in high yield.

Acrylic Resins↗
PubMed1996

Enhancement of CPP32-like activity in the TNF-treated U937 cells by the proteasome inhibitors.

CPP32, which is most closely related to CED-3 in the apoptotic protease in C. elegance, is activated during apoptosis induced by anti-Fas and TNF. Since processing of CPP32 is important for the activation, we examined the effects of protease inhibitors on CPP32-like activity in the TNF-treated U937 cells. Unexpectedly, proteasome inhibitors (at 5 microM) such as Z-LLnV, Z-LLL, and lactacystin enhanced CPP32-like activity, Ac-DEVD-MCA degrading activity, in the TNF-treated U937 cells in 3 hr, but E64d, cysteine protease inhibitor, did not. These proteasome inhibitors alone did not enhance CPP32-like activity in the untreated U937 cells under the condition used. The proteasome seems to protect the cells from apoptosis by degrading CPP32-like protease or its processing enzyme.

Caspase 3↗
PubMed1996

Lung microvascular pressure profile in acute lung injury.

To clarify the role of microvessels in the development of pulmonary hypertension of acute lung injury, we induced lung edema by oleic acid (OA) in ten artificially perfused cat lungs and measured microvascular pressure. Pulmonary artery pressure (Ppa) and pressure of 30-50 microns arteriole (Parteriole) increased from 19.2 +/- 1.4 and 15.7 +/- 1.0 cmH2O before to 30.5 +/- 5.0 cmH2O and 22.7 +/- 2.4 cmH2O after edema, respectively. Pressure of 30-50 microns venule (Pvenule) and venous occlusion pressure (Pvo) did not change significantly after edema. Double occlusion pressure (Pdo) which represents pulmonary microvascular pressure increased from 14.5 +/- 0.6 to 17.7 +/- 2.0 cmH2O. Pressure gradient in the artery, i.e., between Ppa and Parteriole and in the microvessels, i.e., between Parteriole and Pvenule increased when lung became edematous. Pressure gradient in vein, i.e., between Pvenule to left atrium was not affected by edema. Pdo was in the midst of Parteriole and Pvenule in both edematous and non-edematous lung. In acute lung injury, increase of microvascular resistance was followed by an increase of arterial resistance and caused pulmonary hypertension.

Acute Disease↗
PubMed1996

[A study on peak expiratory flow monitoring maneuver as compared to forced expiratory flow maneuver].

In this study, we tried to clarify the characteristics of peak expiratory flow (PEF) measurement maneuver as a tool of daily monitoring severity of asthma in accordance with peak expiratory flow rate (PEFR) of forced expiratory maneuver. PEF did not differ when measured either in the standing or sitting position. However, obese individuals may have higher PEF when measured in the standing position and subjects with emphysematous change may have higher PEF when measured in the sitting than in the standing position. PEF did not differ when measured either with or without nose clip. Expiration time and volume in PEF measurement requires only one fifth and a half of that of forced expiratory flow volume measurement, respectively. In 36% of asthmatic patients in whom PEF is measured daily, PEF measurements were thought to be measured after inspiring at about 90% of forced vital capacity. Although PEF is a well tolerated useful clinical parameter in the management of bronchial asthma, it has different characteristics from peak expiratory flow rate (PEFR) of forced expiratory volume measurement.

Adult↗
PubMed1995

[Scimitar syndrome with diagnostic MRI findings].

A fifty-year-old woman was admitted to our hospital because of an abnormal shadow on a chest X-ray film. She was asymptomatic. Chest X-ray film showed a scimitar-like vessel in the right lung, dextroposition of the heart, and hypoplasia of the right pulmonary artery. MRI revealed that the scimitar vein was anomalous pulmonary venous return from the right lung. Normal venous return from the right lower lobe to the left atrium was confirmed by pulmonary artery angiography. MRI findings have been useful in the diagnosis of scimitar syndrome.

Female↗