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Biomedical subjects

Kenji Ishihara

Publications and source records attributed to Kenji Ishihara.

At least 19 recordsLinked to original sources
PubMed2006

Nitric oxide production by the vacuolar-type (H+)-ATPase inhibitors bafilomycin A1 and concanamycin A and its possible role in apoptosis in RAW 264.7 cells.

In the mouse leukemic monocyte cell line RAW 264.7, the vacuolar-type (H(+))-ATPase (V-ATPase) inhibitors bafilomycin A1 and concanamycin A induced nitric oxide (NO) production through the expression of inducible nitric-oxide synthase mRNA and its protein and decreased cell growth and survival as determined by 3-(4,5-dimethyl(thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Bafilomycin A1 and concanamycin A activated nuclear factor (NF)-kappaB and activator protein-1 and decreased the level of IkappaB-alpha and increased that of phosphorylated c-Jun N-terminal kinase (JNK). NO production induced by these V-ATPase inhibitors was suppressed by the NF-kappaB inhibitor Bay 11-7082 [(E)3-[(4-methylphenyl)sulfonyl])-2-propenenitrile] and the JNK inhibitor SP600125 [anthra[1,9-cd]pyrazol-6(2H)-one] in parallel with the partial alleviation of the V-ATPase inhibitor-induced decrease in MTT response. The Na(+),K(+)-ATPase inhibitor dibucaine and the F-ATPase inhibitor oligomycin did not induce NO production at which concentrations the MTT response was decreased. The NO donor S-nitroso-N-acetyl-dl-penicillamine further lowered the V-ATPase inhibitor-induced decrease in the MTT response, and the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, sodium salt (carboxy-PTIO) alleviated it partially. Mitochondrial depolarization, an index of apoptosis, was induced by bafilomycin A1 and concanamycin A. On treatment with the nitric-oxide synthase inhibitor N(G)-monomethyl-l-arginine acetate, the disruption of mitochondrial membrane potential induced by bafilomycin A1 and concanamycin A was alleviated partially in parallel with the decrease in NO production. Carboxy-PTIO also alleviated it partially. Our findings suggest that the V-ATPase inhibitors bafilomycin A1 and concanamycin A similarly induce NO production and the newly produced NO participates partially in the V-ATPase inhibitor-induced apoptosis in RAW 264.7 cells.

Animals↗
PubMed2006

Inhibition of vacuolar-type (H+)-ATPase by the cytostatic macrolide apicularen A and its role in apicularen A-induced apoptosis in RAW 264.7 cells.

Apicularen A and the known vacuolar-type (H(+))-ATPase (V-ATPase) inhibitor bafilomycin A(1) induced apoptosis of RAW 264.7 cells, while apicularen B, an N-acetyl-glucosamine glycoside of apicularen A, was far less effective. Apicularen A inhibited vital staining with acridine orange of the intracellular organelles of RAW 264.7 cells, inhibited the ATP-dependent proton transport into inside-out microsome vesicles, and inhibited the bafilomycin A(1)-sensitive ATP hydrolysis. The IC(50) values of the proton transport were 0.58 nM for apicularen A, 13 nM for apicularen B, and 0.95 nM for bafilomycin A(1). Furthermore, apicularen A inhibited the bafilomycin A(1)-sensitive ATP hydrolysis more potently than apicularen B. F-ATPase and P-ATPase were not inhibited by apicularen A. We concluded that apicularen A inhibits V-ATPase, and thus induces apoptosis in RAW 264.7 cells.

Adenosine Triphosphate↗
PubMed2006

Severe cortical involvement in MV2 Creutzfeldt-Jakob disease: an autopsy case report.

MV2 type sporadic Creutzfeldt-Jakob disease (sCJD) is reported to have a long duration and marked involvement of the cerebral deep gray matter. We describe an autopsied long-surviving sCJD case of MV2. In the early stages, the patient exhibited memory impairment, attention deficit and semantic memory disorder. Diffusion-weighted MRI showed abnormal hyperintensity signals along the cerebral cortex, sparing the thalami and basal ganglia. Pathological observations included: severe spongiosis throughout the cerebral cortex, several kuru plaques and plaque-like PrP deposits in the cerebellum, with only minimal degeneration in the thalami and basal ganglia. Our case suggests that MV2 has a wide clinicopathological spectrum, which ranges from "VV2" to "MM2" type.

Aged↗
PubMed2006

An autopsy case of frontotemporal dementia with severe dysarthria and motor neuron disease showing numerous basophilic inclusions.

We report a clinicopathological study of a patient suffering from frontotemporal dementia (FLD) with severe dysarthria and concomitant motor neuron disease (MND). The patient was a 52-year-old woman with almost simultaneous emergence of severe dysarthria and FTD. The severe dysarthria subsequently evolved into anterior opercular syndrome. Motor neuron signs then emerged, and the patient developed akinetic mutism approximately 2 years after the onset of the disease. The patient died of pneumonia after a 7-year clinical illness. Pathologically, severe and widespread degeneration in the frontal and temporal lobes, including the anterior opercular area, limbic system, basal ganglia, spinal cord and cerebellum, and frequent ubiquitin- and tau-negative basophilic inclusions were observed. The pyramidal tracts and anterior horns of the cervical cord also showed marked degeneration. Cases showing basophilic inclusions reported so far have been divided into two groups: early onset FTD and MND with basophilic inclusions. Our case presented clinicopathological features of both FTD and MND, which suggests that cases showing basophilic inclusions may constitute a clinicopathological entity of FTD/MND.

Autopsy↗
PubMed2006

A metabonomics study of the hepatotoxicants galactosamine, methylene dianiline and clofibrate in rats.

The efficacy of high-resolution (1)H nuclear magnetic resonance ((1)H-NMR) spectroscopy-based metabonomics was studied in a model of rat liver toxicity. Hepatotoxicities were induced in male rats using methylene dianiline, clofibrate and galactosamine. Twenty-four-hr urine from days 1 to 5 after treatment were subjected to (1)H-NMR evaluation of the biochemical effects. Blood were also taken at Days 2, 3 and 5 to examine biochemical changes associated with hepatotoxicities, and histopathological changes were evaluated at termination. Increases in liver enzymes were observed in animals treated with methylene dianiline or galactosamine, and histopathological analysis revealed changes associated with hepatobiliary damage and hepatocellular necrosis in methylene dianiline- and galactosamine-treated animals, respectively. Principal component analysis and statistical Spotfire analyses were used to visualize similarities and differences in urine biochemical profiles produced by (1)H-NMR spectra. The biochemical effects of methylene dianiline and galactosamine were characterized by elevated levels of glucose, fructose, beta-hydroxybutyrate, alanine, acetoacetate, lactate and creatine and decreased levels of hippurate, 2-oxoglutarate, citrate, succinate, trimethylamine-N-oxide, taurine and N-acetylglutamate in rat urine. Clofibrate treatment elevated the levels of N-methylnicotinamide and 3,4-dihydroxymandelate and decreased the levels of 2-oxoglutarate and N-acetylaspartate. This work shows that combinations of (1)H-NMR and pattern recognition are powerful tools in the evaluation of the biochemical effects of xenobiotics in liver.

Aniline Compounds↗
PubMed2006

A case of frontotemporal lobar degeneration with progressive dysarthria.

We investigated the evolution of the neurological and neuropsychological characteristics in a right-handed woman who was 53-years-old at the onset and who showed personality changes and behavioral disorders accompanied by progressive dysarthria. She had hypernasality and a slow rate of speech with distorted consonants and vowels, which progressed as motor disturbances affecting her speech apparatus increased; finally, she became mute two years post onset. Her dysarthria due to bilateral voluntary facio-velo-linguo-pharyngeal paralysis accompanied with automatic-voluntary dissociation fit the description of anterior opercular syndrome. She showed personality changes and behavioral abnormalities from the initial stage of the disease, as is generally observed in frontotemporal degeneration (FTD), and her magnetic resonance image showed progressive atrophy in the frontotemporal lobes; thus, she was clinically diagnosed with FTLD. This patient's symptoms suggest that FTLD, including bilateral anterior operculum degeneration, causes progressive pseudobulbar paretic dysarthria accompanied by clinical symptoms of FTD, which raises the possibility of a new clinical subtype in the FTLD spectrum.

Atrophy↗
PubMed2006

Coronary artery fistula from the left circumflex to the coronary sinus.

A 27-year-old woman, who had received mitral valve repair for mitral regurgitation resulting from infective endocarditis, was admitted for a close examination of abnormal echocardiographic findings in the left atrium. Transthoracic echocardiography showed trivial mitral regurgitation with normal left ventricular contraction and dilatation of the coronary sinus. Auscultation revealed a grade 2 continuous murmur along the left sternal border. Transesophageal echocardiography demonstrated a marked dilatation of the coronary sinus just behind the posterior wall of the left atrium and turbulent blood flow in the dilated coronary sinus. Cardiac catheterization showed no significant step-up of oxygen saturation in the right heart and normal pulmonary artery pressure. Coronary angiography revealed a markedly dilated and tortuous circumflex coronary artery connected to the coronary sinus through a fistula. A left circumflex artery with a fistulous connection to the coronary sinus is extremely rare.

Adult↗
PubMed2006

[Parkinsonism secondary to chronic subdural hematoma. A case report].

We described a case of secondary parkinsonism due to chronic subdural hematoma (CSH). An 83-year-old man developed memory impairment and gait disturbance gradually since one year ago, and these symptoms subacutely deteriorated after he fell down and hit his head. On admission he had moderate cognitive impairment, gait disturbance (wide-based, small steps and initial freezing), postual instability, akinesia and right-sided rigidity. He did not have resting tremor. A CT scan showed a right-sided CSH with marked compression on the left hemisphere, and remarkable decrease of the blood flow in the left cerebral hemisphere was revealed by single photon emission computed tomography. His neurological condition improved gradually through the decrease of the CSH, which suggested the diagnosis of secondary parkinsonism due to CSH. We thought that the CSH in the right hemisphere caused right-sided parkinsonism through mechanical compression to the left hemisphere, which was shown in the SPECT image, in this case. Elderly people suffering from subacute progressive parkinsonism, should undergo CT studies be to differentiate the parkinsonism secondary to CSH.

Aged, 80 and over↗
PubMed2005

Mechanism of the eosinophilic differentiation of HL-60 clone 15 cells induced by n-butyrate.

n-Butyrate is one of the most powerful chemical inducers of the differentiation of human eosinophilic leukemia HL-60 clone 15 cells into mature eosinophils. We have recently reported that the mechanism by which HL-60 clone 15 cells differentiate into eosinophils by n-butyrate is that n-butyrate continuously inhibits histone deacetylase activity as a histone deacetylase inhibitor, resulting in continuous acetylation of histones. In this review, we discuss roles of histone acetyltransferase, histone deacetylase and histone deacetylase inhibitors in the differentiation of HL-60 clone 15 cells into eosinophils.

Acetylation↗
PubMed2005

Induction of apoptosis by apicularen A in human promyelocytic leukemia cell line HL-60.

Apicularen A, a macrolide isolated from the myxobacterial genus Chondromyces, suppressed the proliferation of human promyelocytic leukemia cells (HL-60 cells), increased the release of lactate dehydrogenase and induced condensation and fragmentation of chromatin at 1 to 100 nM. In addition, it induced the DNA fragmentation, increased the percentage of annexin V-stained cells, and cleaved poly(ADP-ribose) polymerase (PARP), a substrate of caspase. In contrast, apicularen B, an N-acetylglucosamine glycoside of apicularen A, had no such effects at 100 nM. These findings indicated that apicularen A induces apoptosis in HL-60 cells by activating caspases. Phosphorylation of p44/42 MAPK, p38 MAPK and Akt was not induced by apicularen A at 100 nM, suggesting that the apicularen A-induced apoptosis in HL-60 cells is not regulated by the activation of p44/42 MAPK, p38 MAPK or Akt. Furthermore, by acridine orange staining of the cells, it was suggested that apicularen A but not apicularen B inhibits vacuolar-type H+-ATPase.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Argyrophilic grain disease presenting with frontotemporal dementia: a neuropsychological and pathological study of an autopsied case with presenile onset.

A right-handed Japanese man with no consanguinity exhibited personality changes, speech disorder and abnormal behaviors, such as stereotypical, running-away, environment-dependent, and going-my-way behaviors, since the age of 49 years. At age 52 years, neuropsychological examination revealed frontal lobe dysfunctions, mild memory impairment, and transcortical sensory aphasia. MRI showed symmetrical severe atrophy of the anterior part of the temporal and frontal lobes. The clinical diagnosis was FTD. He died at age 54 years after a clinical illness of approximately 5 years. Numerous argyrophilic grains were observed throughout the limbic system, temporal lobe, frontal lobe and brainstem. In addition, there were many tau-positive neurons and glial cells. These findings are all compatible with argyrophilic grain disease (AGD). Our case, however, is atypical AGD because of the young age of onset of the disease and sharply circumscribed cortical atrophy exhibiting severe neuronal loss and gliosis. Our case, together with some other similar cases of atypical AGD, gives rise to the possibility that this type of AGD would constitute a part of pathological background of FTD.

Adult↗
PubMed2005

[Role of eosinophils in allergic inflammation].

Eosinophils are one of the cells that play a critical role in the pathogenesis of allergic diseases. The increase in the number of eosinophils in such diseases is regulated by interleukin-5 (IL-5). The author have prepared recombinant rat IL-5 using a baculovirus expression system and examined its biological activities in rat eosinophils. It was demonstrated that recombinant rat IL-5 prolongs the survival of mature eosinophils and differentiates immature eosinophils into mature eosinophils, suggesting that rat IL-5 is a factor for eosinophilia in rats. Recombinant rat eosinophil-associated ribonuclease (Ear)-1 and Ear-2 were also prepared. Eosinophil granule proteins are thought to cause tissue damage due to their cytotoxic activity, but using recombinant rat Ear-1 and Ear-2, it was found that rat Ear-1 and Ear-2 have strong RNase A activity and bactericidal activity, suggesting that these proteins play critical roles in host defense. Finally, the important role of acetylation of histones was clarified in the differentiation of HL-60 clone 15 cells into eosinophils using the histone deacetylase inhibitors sodium n-butyrate, apicidin, and trichostatin A. These findings would be useful for further investigations of the role of eosinophils in allergic inflammation.

Acetylation↗
PubMed2005

Inhibitory effect of porphyran, prepared from dried "Nori", on contact hypersensitivity in mice.

Porphyran is a major component of the red algae, Porphyra tenera and P. yezoensis, which are processed into a sheet type of dried food, "Nori". Porphyran has been reported to activate murine macrophages by in vitro and i.p. injection studies. The contact hypersensitivity (CHS) reaction in mice is commonly used as a model to evaluate the anti-allergic activity of food and food components. We therefore studied the effect of porphyran on the CHS reaction in Balb/c mice to evaluate anti-allergic activity of porphyran. We found that an oral administration of porphyran (2% in drinking water) suppressed the CHS reaction (ear edema) induced by 2,4,6-trinitrochlorobenzene. We also found that porphyran suppressed the serum level of IgE and the production of interferon-gamma (IFN-gamma) in the challenged ear lobe. We conclude from these results that the CHS reaction was suppressed by oral porphyran due to the decreased serum level of IgE and the production of IFN-gamma in the challenged ear lobe.

Animals↗
PubMed2005

[An autopsied case of medullary glioma with an abrupt onset of headache and hemiparesis].

We describe an 89-year-old woman who presented with an abrupt onset of headache and right hemiparesis. With the initial diagnosis of cerebral infarction, we started therapy using sodium ozagrel. The right hemiparesis worsened, however, and a continuous intravenous heparin injection showed no effect. Furthermore, nystagmus in the bilateral eyes, dysphagia, left hemiparesis, and central ventilation disorder appeared one after another in three weeks. A magnetic resonance images (MRI) of the head, performed on the fifth hospital day with regular intervals of axial sections, disclosed no lesion responsible for right hemiparesis. MRI of the brainstem and upper cervical cord, performed after two weeks with smaller intervals of axial sections, revealed a T2 high signal lesion in the left side of the medulla oblongata and upper cervical cord. After about five weeks from the onset of the disease, she died of pneumonia. With the pathological examination, we diagnosed as glioma originated in the left ventral part of medulla oblongata. Five similar cases of brainstem glioma have been reported so far. Our patient, the oldest one, showed an exceptionally rapid clinical course, instructing us to consider the possibility of medullary glioma even in the elderly patients presenting with acute onset hemiparesis followed by rapid and progressive appearance of brainstem signs.

Aged↗
PubMed2005

[An autopsied case of paraneoplastic neurologic syndrome (limbic encephalitis, cerebellar degeneration, and pseudohypertrophy in the inferior olivary nuclei) associated with T cell lymphoma].

We describe a patient with paraneoplastic neurologic syndrome confirmed on postmortem examination. This 42-year-old man was admitted due to general fatigue, emaciation and acute-onset disorientation. Neurological examination revealed disorientation, moderate cognitive impairment, cerebellar ataxia, bilateral limitations and nystagmus in all directions during external ocular movement, swallowing disorder, bilateral Babinski sign, sensory disturbance in the distal parts of all extremities, and Romberg's sign. T-cell lymphoma was diagnosed following biopsy of the cervical lymph node. Neurological condition improved slightly after chemotherapy, but subsequently deteriorated. At about 6 years after the disease onset, brain magnetic resonance imaging (MRI) revealed atrophy of bilateral hippocampi and the upper vermis of the cerebellum. The patient died of pneumonia after a clinical course of about 6 years and 6 months. Pathologically, neuronal loss, reactive gliosis and perivascular lymphocytic infiltration were observed in the hippocampi, cerebellum, and inferior olivary nuclei. Lymphocytes around the vessels were positive for LCA and UCHL-1, but negative for CD8 and L26, and thus were considered to be T cells. No lymphoma cell was observed in the central nervous system or lymphatic organs. Based on the pathological findings, paraneoplastic neurologic syndrome (limbic encephalitis, cerebellar degeneration and olivary pseudohypertrophy) associated with T-cell type malignant lymphoma was diagnosed. Only three other cases of paraneoplastic neurologic syndrome associated with T-cell lymphoma have been reported. In those cases, death occurred due to the deterioration of malignant lymphoma, whereas the present patient died about 6 years after the remission of malignant lymphoma. Prognosis may thus depend on the course of the malignant lymphoma. In the present patient, neurological symptoms deteriorated after remission of malignant lymphoma, and no pathological lesion were found in the lymphatic organs. Lesions in the central nervous system in paraneoplastic neurological syndromes may follow a course independent of the original malignant disease.

Humans↗
PubMed2004

Induction of nitric oxide production by the cytostatic macrolide apicularen A [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14 dihydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)] and possible role of nitric oxide in apicularen A-induced apoptosis in RAW 264.7 cells.

We previously reported that apicularen A [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-3,4,5,6,7,8,9,10-octahydro-7,14 dihydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)], a highly cytostatic macrolide isolated from the myxobacterial genus Chondromyces, induces apoptosis in the mouse leukemic monocyte cell line RAW 264.7. To analyze the action mechanism of apicularen A for the induction of apoptosis, effects of apicularen A on nitric oxide (NO) production in RAW 264.7 cells were examined. It was demonstrated that apicularen A at 10 and 100 nM induced nitrite production, whereas apicularen B [2,4-heptadienamide, N-[(1E)-3-[(3S,5R,7R,9S)-7-[[2-(acetylamino)-2-deoxy-beta-d-glucopyranosyl]oxy]-3,4,5,6,7,8,9,10-octahydro-14-hydroxy-1-oxo-5,9-epoxy-1H-2-benzoxacyclododecin-3-yl]-1 propenyl]-, (2Z,4Z)-(9CI)], an N-acetyl-glucosamine glycoside of apicularen A, had no effect at 100 nM. The apicularen A-induced nitrite production was accompanied by an increase in the level of inducible nitric-oxide synthase (iNOS) and its mRNA and was suppressed by the NOS inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA). In addition, apicularen A activated nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) and decreased the level of IkappaB-alpha and increased that of phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, the apicularen A-induced nitrite production was suppressed by the NF-kappaB inhibitor Bay 11-7082 [(E)-3-(4-methylphenylsulfonyl)-2-propenenitrile] and the JNK inhibitor SP600125 [anthra[1,9-cd]pyrazol-6(2H)-one]. These findings suggested that apicularen A activates NF-kappaB and AP-1, thus triggering the expression of iNOS mRNA and iNOS protein and induces NO production. Finally, apicularen A decreased cell growth and survival and cell viability and disrupted the mitochondrial membrane potential. The addition of l-NMMA partially recovered the apicularen A-induced decrease in cell growth and survival and cell viability and the disruption of mitochondrial membrane potential. These findings suggested that NO produced by apicularen A treatment participate partially in the apicularen A-induced apoptosis in RAW 264.7 cells.

Animals↗