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Biomedical subjects

K Irie

Publications and source records attributed to K Irie.

At least 91 records · Page 5Linked to original sources
PubMed1998

Radicicol leads to selective depletion of Raf kinase and disrupts K-Ras-activated aberrant signaling pathway.

Activation of Ras leads to the constitutive activation of a downstream phosphorylation cascade comprised of Raf-1, mitogen-activated protein kinase (MAPK) kinase, and MAPK. We have developed a yeast-based assay in which the Saccharomyces cerevisiae mating pheromone-induced MAPK pathway relied on co-expression of K-Ras and Raf-1. Radicicol, an antifungal antibiotic, was found to inhibit the K-ras signaling pathway reconstituted in yeast. In K-ras-transformed, rat epithelial, and K-ras-activated, human pancreatic carcinoma cell lines, radicicol inhibited K-Ras-induced hyperphosphorylation of Erk2. In addition, the level of Raf kinase was significantly decreased in radicicol-treated cells, whereas the levels of K-Ras and MAPK remained unchanged. These results suggest that radicicol disrupts the K-Ras-activated signaling pathway by selectively depleting Raf kinase and raises the possibility that pharmacological destabilization of Raf kinase could be a new and powerful approach for the treatment of K-ras-activated human cancers.

Animals↗
PubMed1998

Morphological and immunocytochemical characterization of primary osteogenic cell cultures derived from fetal rat cranial tissue.

Enzymatic digestion of bone tissue potentially releases a mixture of precursor, differentiating, and mature cells. Conceptually, early fetal osteogenic tissue should provide a more uniform population of cells than late embryonic or newborn bone in which cells have already differentiated. In this context, we have applied sequential enzymatic digestion to obtain and culture cells from 15-16-day fetal rat cranial tissue, a developmental age where deposition of bone matrix has not yet started at this site. These cultures were compared with those of osteogenic cells isolated from newborn rat calvariae and grown under similar conditions. Matrix production and composition were examined by colloidal gold immunocytochemistry using antibodies to bone sialoprotein (BSP), osteocalcin (OC), and osteopontin (OPN). The plated cells formed mineralized nodules by day 14. The presence of mineral was determined by von Kossa staining and backscattered electron imaging (BEI), and the accumulation of calcium and phosphorus within the nodules was demonstrated by X-ray microanalysis and elemental mapping. At early time intervals, cells were generally cuboidal in shape and showed a well-developed Golgi apparatus, which occasionally was immunoreactive for OPN. Labeling for BSP and OPN was found over mineralization foci and electron-dense material within, and at the periphery, of larger mineralized masses and over accumulations of afibrillar matrix at the dish surface. Osteocalcin immunoreactivity was also associated with electron-dense portions of the bone-like matrix. These data demonstrate the potential of presumptive fetal rat calvarial cells to form a bone-like matrix in vitro and suggest that the assembly and mineralization pattern show similarities to the process of intramembranous ossification. Such a culture system is of interest not only for studying cellular and matrix events of bone formation, but also factors which influence mesenchymal cells in committing themselves to the osteogenic pathway.

Animals↗
PubMed1998

Cerebral blood flow and metabolism in patients with silent brain infarction: occult misery perfusion in the cerebral cortex.

OBJECTIVES: Silent brain infarction (SBI) is of growing interest as a possible risk factor for symptomatic stroke. Although morphological characteristics of SBI have been well defined, their characteristic patterns of cerebral blood flow (CBF) and metabolism are in dispute. The purpose of this study was to elucidate CBF and metabolism in patients with SBI in relation to symptomatic stroke. METHODS: The patients underwent PET and were separated into three groups; control group (C group), with no lesions on CT (n=9, mean age 57), SBI group, with no neurological signs or history of stroke, but with ischaemic lesions on CT (n=9, mean age 63), and brain infarction group (BI group), with neurological deficits and compatible CT lesions in the area supplied by perforating arteries (n=19, mean age 56). Regional CBF, oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2), and cerebral blood volume (CBV) were measured by PET. RESULTS: Mean values for CBF to the cerebral cortex and deep grey matter were lower in the SBI group (31.6 (SD 5.8) and 34.3 (SD 6.9) ml/100 g/min, respectively) and in the BI group (30.8 (SD 5.2), 33.9 (SD 5.9), respectively) than in the C group (36.0 (SD 6.6) and 43.5 (SD 9.5), respectively). Although mean CMRO2 of deep grey matter (2.36 (SD 0.52) ml/100 g/min) was significantly decreased in the SBI group compared with the C group (2.76 (SD 0.480), p<0.01), CMRO2 of the cortical area was as well preserved in the SBI patients (2.36 (SD 0.39)) as in the controls (2.48 (SD 0.32)) with a compensatory increase of mean OEF (0.45 (SD 0.06) and 0.41 (SD 0.05), respectively). CONCLUSIONS: Patients with SBI showed decreased CBF and CMRO2 in deep grey matter. On the other hand, decreased CBF with milder increased OEF, resulting in preserved CMRO2 in the cerebral cortex indicates the presence of occult misery perfusion, suggesting that patients with SBI have reduced cerebral perfusional reserves.

Adult↗
PubMed1998

A new method to improve in-bore middle cerebral artery occlusion in rats: demonstration with diffusion- and perfusion-weighted imaging.

BACKGROUND AND PURPOSE: In-bore middle cerebral artery occlusion (MCAO) enables investigators to acquire preischemic MRI data and to image ischemic changes immediately after occlusion. We have developed a highly successful in-bore MCAO method. This study describes the methods and pertinent techniques. METHODS: Sixty-seven Sprague-Dawley rats were subjected to temporary (n=36) or permanent (n=31) MCAO. The occluding device consisted of a supporting tubing, a driving line, and a silicone-coated 4-0 nylon suture occluder. Outside the magnet, the occluder was positioned in the carotid canal. MCAO was achieved in the magnet bore by remotely advancing the driving line until resistance was felt. Diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) were acquired before and immediately after occlusion and were used to document the presence of MCAO. RESULTS: Fifty-nine (88.1%) rats were successfully occluded, demonstrating hyperintensity on DWI, perfusion deficits on PWI, and no subarachnoid hemorrhage at postmortem examination. The average values of the apparent diffusion coefficient in both the frontoparietal cortex and the lateral caudoputamen significantly decreased as early as 3 minutes after the onset of ischemia. The failures included preocclusion damage (1/67), sliding out of the occluder during occlusion (1/67), no occlusion (2/67), and arterial perforation (4/67). CONCLUSIONS: Our in-bore MCAO method is easily performed and is as successful as MCAO induced outside the magnet.

Animals↗
PubMed1998

The value of colour Doppler ultrasonography for small bowel involvement of adult Henoch-Schönlein purpura.

Three patients presented with a non-thrombocytopenic purpuric rash on their upper and lower limbs, abdominal pain, diarrhoea, and arthralgia. Grey scale ultrasound showed abnormally thickened walls of the small bowel. Colour Doppler showed blood flow signals in the diseased bowel wall in all patients. Subsequent barium and endoscopic studies showed oedematous bowel loops with petechial lesions. Biopsy from the purpuric rash of the skin demonstrated vasculitis of subdermal small vessels. The clinical diagnosis of Henoch-Schönlein purpura was made in each case. This paper describes the efficacy of grey scale and colour Doppler ultrasonography in the assessment of the small bowel involvement of Henoch-Schönlein purpura.

Adult↗
PubMed1998

Synthesis and biological activities of (-)-6-n-octyl-indolactam-V, a new potent analogue of the tumor promoter (-)-indolactam-V.

(-)-Indolactam-V (1) without a hydrophobic chain at positions 6 and 7 of the indole ring is a weak tumor promoter compared with teleocidin Bs. To investigate the effects of the hydrophobic substituent at position 6 of teleocidin Bs, we synthesized (-)-6-n-octyl-indolactam-V (2) by a palladium-catalyzed coupling reaction from (-)-6-bromo-indolactam-V (7) which had been obtained by microbial conversion with Streptoverticillium blastmyceticum NA34-17 as the key step. (-)-7-n-Octyl-indolactam-V (3) with potent biological activities comparable to those of teleocidin Bs was similarly synthesized from (-)-7-bromo-indolactam-V as a positive control. Compound 2 showed similar biological activities to those of 3, indicating that the effect of the hydrophobic substituent at position 6 of 1 was identical to that at position 7.

Antigens, Viral↗
PubMed1998

Spinal cord hemangioblastoma presenting with subarachnoid hemorrhage.

A 41-year-old man presented with subarachnoid hemorrhage (SAH) caused by a cervical spinal cord hemangioblastoma. There were no features to distinguish the SAH from that due to an intracranial lesion. The diagnosis was established by cerebral angiography, computed tomography, and magnetic resonance imaging. The tumor was located in the right dorsolateral aspect of the cervical spinal cord. Hemilaminectomy was performed, and the tumor was completely removed. No postoperative neurological deficit was observed. The possibility of a spinal origin for SAH should be considered if no cranial origin can be detected.

Adult↗
PubMed1998

Large and giant middle to lower basilar trunk aneurysms treated by surgical and interventional neuroradiological methods.

Treatment of large and giant aneurysms of the basilar artery remains difficult and controversial. Three large or giant aneurysms of the lower basilar artery were treated with a combination of surgical and interventional neuroradiological procedures. All patients underwent the balloon occlusion test with hypotensive challenge (blood pressure reduced to 70% of the control value). The third patient did not tolerate the test. In the first patient, both vertebral arteries were occluded through a craniotomy. In the second patient, both the aneurysm and the basilar artery were occluded by detached balloons. In the third patient, one vertebral artery was occluded by surgical clipping and the other by detached helical coils and fiber coils. In spite of anti-coagulation and anti-platelet therapy, postoperative thrombotic or embolic ischemia occurred in the second and third patients. Fibrinolytic therapy promptly corrected the ischemic symptoms, but the second patient developed hemorrhagic complications at the craniotomy area 2 hours later. At follow-up examination, the first patient had only 8th cranial nerve paresis, the second patient who had a hemorrhagic complication was bed-ridden, and the third patient had no deficit. Interventional occlusion requires a longer segment of the parent artery compared to surgical occlusion of the parent artery and might cause occlusion of the perforating arteries. However, selected use of various coils can occlude only a short segment of the parent artery. Thus, the postoperative management of thromboembolic ischemia after the occlusion of the parent artery is easier using the interventional technique.

Adult↗
PubMed1998

Quadriceps atrophy after partial resection of the patellar tendon: an experimental study in a rat model.

Quadriceps muscle atrophy of rats was examined after resection of the central third (group 1) or the lateral two thirds (group 2) of the patellar tendon, the tensor fascia lata (group 3), or the medial hamstring (group 4). The quadriceps atrophied in groups 1 and 2, and more so in group 2, but there was no atrophy in groups 3 or 4. Thus, after an anterior cruciate ligament reconstruction procedure using the patellar tendon, resection of the patellar tendon itself leads to quadriceps atrophy and the extent of atrophy is related to the resected width.

Animals↗
PubMed1998

Cytologic and genetic study of polyomavirus-infected or polyomavirus-activated cells in human urine.

OBJECTIVE: To carry out a morphologic and genetic study of human polyomavirus infection or activation in child and adult urine specimens. DESIGN AND SETTING: The study was carried out on 16 urine samples from children with human polyomavirus infection and 104 samples from adults with virus activation identified among 18800 consecutive urine samples (0.64%). RESULTS: All specimens from children showed numerous typical intranuclear inclusion-bearing (INIB) cells. All adult specimens with cytological features similar to childhood specimens were defined as type 1 adult cases. We identified 14 adult cases with marked immunologic suppression as type 1 cases. The inclusions were large, homogeneous, and basophilic, and they were mainly attributable to the BK virus, as demonstrated by a polymerase chain reaction. These infected or activated cells revealed features demonstrating their origin in the superficial transitional epithelium of the urinary tract. Adult cases with different cytologic features were designated as type 2 adult cases. In type 2 adult cases, the number of virus-activated cells was lower, and degenerated intranuclear inclusion-bearing cells with a coarse chromatin pattern were observed in most cases. These characteristics were identified in 90 adults without immunologic suppression. A polymerase chain reaction with BamHI digestion demonstrated JC virus DNA in nearly all of these specimens. CONCLUSION: The JC virus-activated cells found in type 2 adult cases and the BK virus-infected cells found in childhood cases were not of clinical importance. However, the BK virus-activated cells associated with immunologic suppression may have prognostic significance.

Adult↗
PubMed1998

[A case report of aortic regurgitation associated with rheumatic arthritis].

We report a rare case of aortic regurgitation (AR) associated with rheumatic arthritis (RA). A 61-year-old female was admitted to our hospital with severe heart failure due to AR. She had a 8-year history of RA and had been treated with steroid therapy. Trans-esophageal echocardiography showed thickness and shortening of non coronary cusp (NCC) of aortic valve. After treated for heart failure, aortic valve replacement with SJM-HP 17 mm was done. At operation, right and left coronary cusps were almost normal, but NCC was thickened and shortened. The valve of NCC histology showed granuloma. She recovered uneventfully. Two cases of cardiac valvular disease, associated with granuloma of RA, were reported in Japan. We discussed these cases in this paper.

Aortic Valve↗
PubMed1998

Obstructive jaundice due to multiple hepatic abscesses.

A 63-year-old Japanese male with diabetes mellitus developed obstructive jaundice following the onset of multiple hepatic abscesses. Percutaneous transhepatic cholangiography showed intrahepatic bile duct irregularity and dilatations accompanied by a complete obstruction of the right branch of the intrahepatic bile duct. Three kinds of organisms were cultured from the blood and the drained bile. The cholangiographic changes returned to the normal after the liver abscesses subsided following biliary drainage and the administration of intravenous antibiotics.

Bacteroides Infections↗
PubMed1997

Cationic amino acid transporter-2 mRNA induction by tumor necrosis factor-alpha in vascular endothelial cells.

Nitric oxide (NO) synthesis may be coupled to the activity of the cellular L-arginine transporter, namely the cationic amino acid transporter. The present study examined tumor necrosis factor (TNF)-alpha-induced alterations in the gene expression of the cationic amino acid transporter (CAT) and NO production in human umbilical vein endothelial cells. In quiescent endothelial cells, CAT-1 mRNA expression, determined by reverse transcription-polymerase chain reaction, was dominant to that of CAT-2. TNF-alpha (10 ng/ml for 1-24 h) induced a time-dependent increase in CAT-2 but not CAT-1 expression. Moreover, TNF-alpha (1-30 ng/ml) treatment for 6 h induced a concentration-dependent increase in CAT-2 mRNA expression. The upregulation of CAT-2 expression by TNF-alpha was associated with enhanced nitrite accumulation in the culture medium (70% increase compared with vehicle-treated cells at 24 h). Thus, induction of the cationic amino acid transporter may constitute one mechanism for the TNF-alpha-induced NO production in human umbilical vein endothelial cells.

Amino Acid Transport Systems, Basic↗
PubMed1997

Nitric oxide mediates down regulation of lipoprotein lipase activity induced by tumor necrosis factor-alpha in brown adipocytes.

We previously reported that tumor necrosis factor-alpha (TNF-alpha)/cachectin suppresses lipoprotein lipase activity and its gene expression in brown adipocytes differentiated in culture. Recent evidence suggests that the effect of TNF-alpha over various cells is related to the enhanced production of nitric oxide (NO). The present study examined whether the suppressive effect of TNF-alpha on lipoprotein lipase activity is mediated by production of NO in the brown adipocytes. A reverse transcription-polymerase chain reaction (RT-PCR) assay revealed that TNF-alpha caused a concentration- and time-dependent expression of inducible NO synthase in brown adipocytes. Increasing concentrations of TNF-alpha (0.5-50 ng/ml) for 24 h resulted in a concentration-dependent decrease in lipoprotein lipase activity with reciprocal increase in nitrite production in the medium. The suppressive effect of TNF-alpha on lipoprotein lipase activity was significantly prevented by NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and aminoguanidine, but not by D-NAME, an inactive isomer. Furthermore, 8-bromoguanosine 3',5'-cyclic monophosphate, cell permeant cGMP, suppressed lipoprotein lipase activity and 1 H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one, a selective inhibitor for soluble guanylate cyclase, restored the TNF-alpha-suppressed lipoprotein lipase activity. These results suggest that TNF-alpha stimulates brown adipocytes to express inducible NO synthase, followed by production of NO, which in turn mediates the suppressive effect of TNF-alpha on lipoprotein lipase activity. The effect of NO is mediated, at least partly, through production of cGMP.

Adipocytes↗
PubMed1997

The prognostic significance of p53 and bcl-2 expression in lung adenocarcinoma and its correlation with Ki-67 growth fraction.

BACKGROUND: The p53 and bcl-2 gene deregulations are frequently involved in several types of epithelial malignancy. The aims of this study were to determine the relationships between the Ki-67 labeling index (LI) and the expression of p53 and bcl-2 protein in lung adenocarcinoma and to investigate the clinicopathologic features of the tumors and the prognostic significance of p53 and bcl-2. METHODS: Immunohistochemical staining for p53, bcl-2, and Ki-67 was performed on paraffin embedded sections from 114 lung adenocarcinomas from patients who had been treated with complete and potentially curative surgery. To define a cutoff value for p53 immunopositivity, 37 of 114 tumors were examined for p53 gene mutations using cDNA sequencing. The results were compared with clinical outcomes. RESULTS: Expression of p53 protein was defined as nuclear staining in more than 20% of tumor cells, and the concordance rate between p53 expression and gene mutation was 73%. Expression of p53 (39%) was significantly associated with higher Ki-67 LI (P < 0.001) and with several poor prognostic factors, such as poor histologic grade of differentiation (P < 0.05), lymphatic permeation (P < 0.001), and vascular permeation (P < 0.001). Expression of bcl-2 (38%) was significantly associated with favorable T classification (P < 0.001) and smaller tumor size (<2 cm) (P < 0.05) and tended to be associated with lower Ki-67 LI (P = 0.054). In univariate analysis, p53 expression was significantly correlated with poor prognosis (53% vs. 90% at 5 years, P < 0.001) and bcl-2 expression with favorable prognosis (90% vs. 68% at 5 years, P < 0.05). Proliferative activity was highest when only p53 was expressed; by contrast, proliferative activity was lowest when only bcl-2 was expressed. Among four groups of patients, the group that was positive only for p53 had the shortest survival; this difference was statistically significant. Multivariate analysis showed that T classification (P = 0.002), vascular permeation (P = 0.011), and p53 expression (P = 0.03) were independent prognostic factors. CONCLUSIONS: The results of this study indicated an inverse relationship between the proliferative activity of p53 and bcl-2. Expression of p53 was an independent factor associated with poor prognosis, whereas bcl-2 expression was associated with favorable prognosis.

Adenocarcinoma↗
PubMed1997

TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase.

Ceramide has been proposed as a second messenger molecule implicated in a variety of biological processes. It has recently been reported that ceramide activates stress-activated protein kinase (SAPK, also known as c-Jun NH2-terminal kinase JNK), a subfamily member of mitogen-activated protein kinase superfamily molecules and that the ceramide/SAPK/JNK signaling pathway is required for stress-induced apoptosis. However, the molecular mechanism by which ceramide induces SAPK/JNK activation is unknown. Here we show that TAK1, a member of the mitogen-activated protein kinase kinase kinase family, is activated by treatment of cells with agents and stresses that induce an increase in ceramide. Ceramide itself stimulated the kinase activity of TAK1. Expression of a constitutively active form of TAK1 resulted in activation of SAPK/JNK and SEK1/MKK4, a direct activator of SAPK/JNK. Furthermore, expression of a kinase-negative form of TAK1 interfered with the activation of SAPK/JNK induced by ceramide. These results indicate that TAK1 may function as a mediator of ceramide signaling to SAPK/JNK activation.

Animals↗
PubMed1997

Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK/JNK and p38 signaling pathways.

Mitogen-activated protein (MAP) kinase cascades are activated in response to various extracellular stimuli, including growth factors and environmental stresses. A MAP kinase kinase kinase (MAPKKK), termed ASK1, was identified that activated two different subgroups of MAP kinase kinases (MAPKK), SEK1 (or MKK4) and MKK3/MAPKK6 (or MKK6), which in turn activated stress-activated protein kinase (SAPK, also known as JNK; c-Jun amino-terminal kinase) and p38 subgroups of MAP kinases, respectively. Overexpression of ASK1 induced apoptotic cell death, and ASK1 was activated in cells treated with tumor necrosis factor-alpha (TNF-alpha). Moreover, TNF-alpha-induced apoptosis was inhibited by a catalytically inactive form of ASK1. ASK1 may be a key element in the mechanism of stress- and cytokine-induced apoptosis.

Amino Acid Sequence↗