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Biomedical subjects

K Irie

Publications and source records attributed to K Irie.

At least 55 records · Page 3Linked to original sources

Anti-NO action of carvedilol in cell-free system and in vascular endothelial cells.

1. Carvedilol, an adrenoceptor blocker with antioxidant activity, was studied for its ability to interact with NO in a cell-free condition and in an endothelial cell line (ECV304). 2. In a cell-free system, carvedilol attenuated NO-dependent reduction of carboxy-2-phenyl-4,4, 5,5-tetramethyl-imidazoline-1-oxyl-3-oxide induced by a NO donor, 1-hydroxy-2-oxo-3-(aminopropyl)-3-isopropyl-1-triazene (NOC5), which was determined by electron paramagnetic resonance (EPR) spectrometry. The EPR study also showed that nitrosylhaemoglobin formation in rat red blood cells by the addition of NO-saturated solution was attenuated by prior incubation with 0.1 - 10 microM carvedilol. 3. NO-induced fluorescence in 4,5-diaminofluorescein-2 diacethyl (DAF-2DA)-loaded ECV304 cells was attenuated by carvedilol but not by labetalol. The IC(50) of carvedilol for NOC5 or sodium nitroprusside-induced fluorescence of DAF-2DA in ECV304 cells was 1. 0x10(-7) M, which was similar to the reported IC(50) of carvedilol for the antioxidant effect. 4. Cell toxicity induced by a NO donor determined by the number of viable cells after 24 h treatment with 2-2'(hydroxynitrosohydrazino)bis-ethanamine was significantly attenuated by pretreatment with 1 microM carvedilol. 5. Both free and cell-associated carvedilol quenched NO. Because NO mediates both physiological and pathophysiological processes, NO quenching by the drug may have diverse clinical implications depending upon specific functions of local NO in tissues where carvedilol is distributed.

Animals↗

Evaluation of iNOS-dependent and independent mechanisms of the microvascular permeability change induced by lipopolysaccharide.

1. Subcutaneous injection of lipopolysaccharide (LPS) increases plasma leakage in mouse skin. Pretreatment with LPS conditions mice tolerant to the LPS-induced plasma leakage. Nitric oxide (NO) has been suggested to be involved in these LPS effects. A specific role of inducible NO synthase (iNOS) was investigated in the LPS-induced plasma leakage using iNOS deficient mice. 2. Plasma leakage in mouse skin was measured by the local accumulation of Pontamine sky blue at the site of subcutaneous injection of LPS (Sal. typhimurium). LPS (100 - 400 microg site(-1)) produced a dose-related increase in dye leakage in both iNOS deficient and wild-type mice with about 40% less dye leakage in iNOS deficient mice. 3. Indomethacin (5 mg kg(-1)), N-[-2-cyclohexyloxy]-4-nitrophenyl methanesulphonamide (NS-398) (1 mg kg(-1)), diphenhydramine (10 mg kg(-1)) and anti-TNF-alpha antibody (dilution 1 : 400, 10 ml kg(-1)) inhibited the LPS-induced dye leakage in both iNOS deficient and wild-type mice, whereas N(G)-nitro-L-arginine methyl ester (L-NAME) (10 mg kg(-1)) or aminoguanidine (10 mg kg(-1)) inhibited that in wild-type but not in iNOS deficient mice. 4. Pretreatment with LPS (0.15 mg kg(-1) i.p.) 4 h before decreased the LPS-induced dye leakage in wild-type but not in iNOS deficient mice. LPS pretreatment increased serum corticosterone levels in both mice, while it increased the serum nitrate/nitrite levels in wild-type but not in iNOS deficient mice. 5. These studies indicate that an increase in vascular permeability induced by LPS is mediated by NO produced by iNOS, eicosanoids, histamine and TNF-alpha. The tolerance against LPS-induced vascular permeability change may be mediated by iNOS induction but not by an increased release of endogenous corticosteroids.

Animals↗

Role of inflammatory mediators in lipid A analogue (ONO-4007)-induced vascular permeability change in mouse skin.

1. Endotoxin shock is accompanied by an increase in peripheral vascular permeability. It has been postulated that most biological activities of LPS are derived from lipid A moiety. Here we examined the effect of lipid A analogue ONO-4007 in increasing vascular permeability and the possible mediators in mouse skin by a dye leakage method. 2. Subcutaneous injection of ONO-4007 (1 - 2 mg site(-1)) induced a dose-dependent increase in vascular permeability which was evident after 120 min. 3. ONO-4007-induced dye leakage was significantly attenuated by pretreatments with anti-tumour necrosis factor-alpha (TNF-alpha) and anti-interleukin-1alpha (IL-1alpha) antibodies, but not with indomethacin (5 mg kg(-1)) or diphenhydramine (10 mg kg(-1)). ONO-4007-induced dye leakage was significantly inhibited by a pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) (10 mg kg(-1)) but not with aminoguanidine (50 mg kg(-1)). In inducible nitric oxide synthase (iNOS)-deficient mice, ONO-4007 significantly increased the dye leakage, while ONO-4007 dilated rat thoracic aortic rings pre-contracted with phenylephrine, and the L-NAME pretreatment inhibited the dilation. 4. Thus, TNF-alpha, IL-1alpha and constitutive NOSs-derived nitric oxide but not prostaglandins or histamine play a role in ONO-4007-induced increase in vascular permeability. Although ONO-4007 mimics LPS in increasing vascular permeability, mechanisms of permeability change elicited by ONO-4007 were not identical to those of LPS.

Animals↗

Treatment of arteriovenous malformation of the brain--preliminary experience.

With the availability of new techniques, such as intravascular embolisation and radiosurgery, the therapeutic approach to arteriovenous malformations (AVMs) of the brain has recently been modified. The present study reports the authors, experiences in treating AVMs over the past 13 years. Spetzler-Martin grading of AVMs was I and II in 19 cases, III in 12, IV in 5 and V in 1 case. Four therapeutic regimens were utilised: surgical resection alone, embolisation and resection, and radiosurgery alone or after surgical resection. Generally, for low-grade AVMs (Spetzler-Martin grades I, II and III), the therapeutic choice was surgical resection in 27 cases, in combination with pre-operative embolisation in two of these patients. Two cases received radiotherapy only and one case received radiosurgery after embolisation, while one case was treated conservatively. Of the five cases of grade IV, four required surgical treatment, whereas the fifth case was treated conservatively. Favourable results (good recovery and moderate disability) were obtained in 96% of the low-grade AVMs as compared with the high-grade AVMs (66%) that had a poor outcome (due to primary brain damage resulting from haemorrhage at the onset in three cases and due to postoperative re-bleeding in one case). This report summarises preliminary experience in treating intracranial AVMs by surgical resection, intravascular embolisation and radiotherapy. Good therapeutic results can be expected by combining these therapeutic modalities.

Adult↗

Eruptive vellus hair cyst and epidermoid cyst in a patient with pachyonychia congenita.

We report the first case of pachyonychia congenita (PC) associated with both eruptive vellus hair cyst (EVHC) and epidermoid cyst. The patient is a 12-year-old Japanese girl who presented with two natal teeth at birth. She had thickening and discoloration of the fingernails and toenails, plantar hyperkeratosis, palmar-plantar hyperhidrosis and multiple cutaneous cysts. Histologic examination revealed EVHC and epidermoid cyst.

Axilla↗

A case of CD56+ cutaneous aleukaemic granulocytic sarcoma with myelodysplastic syndrome.

We describe a 70-year-old man with cutaneous granulocytic sarcoma who presented with numerous cutaneous nodules but without any leukaemic involvement of the peripheral blood. The tumour cells were positive for lysozyme, peroxidase, CD11a, CD11c, CD33 and HLA-DR, and weakly positive for CD4 and CD14, suggesting granulocytic differentiation. The bone marrow at admission showed dysplasia of the erythrocytic and granulocytic lineage and complex chromosomal abnormalities in association with an increase in monocytes. The patient was diagnosed as having granulocytic sarcoma of monocytic lineage with concomitant myelodysplastic syndrome. In this case, tumour cells also expressed the neural cell adhesion molecule (CD56), which has been suggested as a possible risk factor for developing granulocytic sarcoma in acute myelogenous leukaemia.

Aged↗

Synthesis and tumor-promoting activities of 12-Epi-phorbol-12,13-dibutyrate.

12-Epi-phorbol-12,13-dibutyrate (1), the C12-epimer of the most frequently used phorbol ester probe, phorbol-12,13-dibutyrate (PDBu), has been synthesized from phorbol in 9 steps in order to investigate the structural requirements for tumor-promoting activity. Compound 1 showed about 100-fold weaker in vitro biological activities related to in vivo tumor promotion, Epstein-Barr virus early antigen (EBV-EA)-inducing ability, superoxide (O2-) generation-inducing ability, and binding to the protein kinase C (PKC) regulatory domain surrogate peptides. The results indicated that the beta-stereochemistry at position 12 of the phorbol skeleton is important for optimal activity. Binding selectivity to each PKC C1 domain of 1 was almost equal to that of PDBu.

Antigens, Viral↗

Immunoreactivity to a monoclonal antibody (OS-3) is shared by osteoclasts and bicarbonate-secreting cells.

OS-3, a monoclonal antibody raised against macrophagic cells derived from cultured rat glomeruli, reacts with the plasma membrane of various bicarbonate-secreting cells such as epithelial cells of the pancreatic excretory duct and type B intercalated cells of the kidney, suggesting that the antigenic molecule of OS-3 is involved in bicarbonate production and/or secretion. Since osteoclasts must vigorously extrude bicarbonate to maintain cytoplasmic pH in a physiologic range during proton secretion, we examined the localization of OS-3 immunoreactivity in the bone tissue to determine the involvement of the detected molecule in the transmembrane transport of bicarbonate in osteoclasts. The OS-3 selectively stained the basolateral plasma membrane of osteoclasts. Ultrastructurally, the immunoreactivity with OS-3 was associated with small cytoplasmic projections and microplicae of the basolateral plasma membrane. This finding suggests that osteoclasts express the molecule common to bicarbonate-secreting cells to utilize it for bicarbonate transport during bone resorption.

Animals↗

Localization of alkaline phosphatase and osteopontin during matrix mineralization in the developing cartilage of coccygeal vertebrae.

We observed the manner in which alkaline phosphatase (ALPase) and osteopontin were localized in the cartilage and intramembranous bone of coccygeal vertebrae during matrix mineralization, shedding considerable light on the manner in which they develop. In the cartilage matrix of coccygeal vertebrae, we observed the localization of ALPase activity in the boundary of the proliferative and the hypertrophic zones. Granular nodules of mineralization were consistently found in the boundary of both zones, and increased in size when close to the hypertrophic zone. While osteopontin was rarely present in the early stages of mineralization, its localization along the margins of mineralized matrices in the hypertrophic zone was prominent. In contrast to cartilage, mineralized nodules in the intramembranous bone in the mid-portion of the vertebra displayed osteopontin-immunoreactivity, indicating its early synthesis and subsequent accumulation to early-stage mineralized nodules. When blood vessels, accompanied by osteoblastic and osteoclastic cell populations, invaded the cartilage, osteopontin was localized in the lower region of the hypertrophic zone, despite its maintaining the localization of ALPase and early-stage mineralization. Thus, our investigation demonstrated ALPase activity consistent with early-stage mineralization in the cartilage matrix. However, the fact that osteopontin-localization could not be pinpointed might account for its multifunctionality as concerns both the regulation of mineralization and the attachment of migrating osteogenic and osteoclastic cells to the mineralized matrix.

Acid Phosphatase↗

Development of colonic necrosis following severe acute pancreatitis.

We herein describe a 70-year-old male patient who developed colonic necrosis following severe acute pancreatitis. He was referred to our hospital with a diagnosis of acute pancreatitis. In the course of the disease, he developed sudden and massive hematochezia and died. The autopsy findings revealed large bowel ischemia with transmural infarction. The possible pathogenic mechanisms of colonic ischemia are also discussed.

Acute Disease↗

Endovascular treatment of basilar tip aneurysm associated with moyamoya disease--case report.

A 58-year-old female was admitted unconscious to a local hospital. Computed tomography demonstrated subarachnoid hemorrhage. Cerebral angiography revealed evidence of moyamoya disease and a saccular aneurysm at the tip of the basilar artery. The patient was transferred to our hospital for embolization of the basilar tip aneurysm. Endovascular embolization was performed using Guglielmi detachable coils (GDCs), and the aneurysm was completely occluded with preservation of the parent artery. No change in the patient's neurological status was seen during and after the procedure. Endovascular treatment using GDCs appears to be particularly suitable for ruptured cerebral saccular aneurysms in patients with moyamoya disease.

Basilar Artery↗

Balloon-assisted coil placement in wide-necked cerebral aneurysms: preliminary clinical experience.

Endovascular treatment of wide-necked cerebral aneurysms with Guglielmi detachable coils (GDCs) has been limited due to coil protrusion into the artery. Seven patients with wide-necked cerebral aneurysms were treated with GDCs with temporary balloon inflation for mechanical protection during coil placement. Transarterial embolization of the aneurysm with GDCs had failed due to coil protrusion into the parent artery. The use of simultaneous temporary balloon protection achieved more dense intra-aneurysmal coil packing, especially in the neck, without compromising the parent artery.

Aged↗

A comparison of magnetic resonance imaging and arthroscopic evaluation of chondral lesions of the knee.

This study compared the sensitivity of magnetic resonance imaging (MRI) to arthroscopy in detecting localized chondral lesions of the knee, especially lesion depth, in 28 patients with 32 femoral and tibial lesions. Average patient age was 24.3 years. Chondral lesions were classified according to five grades. The sensitivity of MRI was 100% for grade 3 (deep) and higher lesions, but was less for superficial chondral lesions. Arthroscopic and MRI grades coincided for only three lesions. Magnetic resonance imaging was not so accurate regarding depth even for deep chondral lesions, although subchondral lesions undetectable by arthroscopy often were detected by MRI.

Adolescent↗

A case of multiple myeloma which developed into multiple extramedullary involvement in the terminal stage.

A 69-year-old man with a diagnosis of multiple IgG class myeloma received combination chemotherapy. He achieved a partial response with an undetected M spike. However, he demonstrated new lytic bone lesions and multiple extramedullary involvement 10 months after the initial presentation. Polymerase chain reaction (PCR) analysis using a framework 3 (Fr3) V-region primer clarified a discrete band in the extramedullary tumor, while it yielded 4 bands including the same size as the extramedullary tumor produced in the bone marrow sample obtained before the chemotherapy. These findings suggest that a resistant and non-secretory clone was selected by the combination chemotherapy.

Aged↗

A new class of simplified phorbol ester analogues: synthesis and binding to PKC and eta PKC-C1B (eta PKC-CRD2).

[formula: see text] A unique class of simplified phorbol ester analogues is described for the first time. A highly efficient retro-annelation sequence was developed in order to remove the five-membered ring from the phorbol diterpene core, allowing access to BCD ring analogues of the phorbol esters. The binding of these analogues to protein kinase C (PKC) and the truncated peptide eta PKC-C1B (eta PKC-CRD2) is also reported.

Animals↗

Synthesis and phorbol ester-binding studies of the individual cysteine-rich motifs of protein kinase D.

To investigate the phorbol ester-binding properties of the individual cysteine-rich motifs of protein kinase D (PKD), the 52-mer peptides containing each cysteine-rich motif of PKD (PKD-C1A, PKD-C1B) have been synthesized. The [3H]phorbol-12,13-dibutyrate (PDBu) binding to PKD-C1A was affected drastically by incubation temperature while that to PKD-C1B was not. Scatchard analysis of [3H]PDBu binding to both PKD C1 peptides gave dissociation constants of 2.5 +/- 0.4 and 2.7 +/- 0.8 nM for PKD-C1A and PKD-C1B, respectively, indicating that the two cysteine-rich motifs of PKD are functionally equivalent like those of PKCgamma.

Amino Acid Sequence↗