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Biomedical subjects

K Irie

Publications and source records attributed to K Irie.

At least 163 records · Page 9Linked to original sources

An autopsy case of B-cell lymphoma associated with macroglobulinemia (IgM-k).

While he was treated for macroglobulinemia showing symptoms, a 65-year-old man developed an enlargement of the left lateral cervical lymph node. Biopsy specimens of the cervical lymph node revealed large-cell non-Hodgkin's lymphoma. The lymphoma cells had rearrangement in the immunoglobulin heavy chain and kappa light chain genes. There was osteolysis involving right metatarsal bones. And, a tumor appeared on the upper hard palate in the terminal stage. Autopsy specimens showed infiltration of lymphoma cells into multiple organs. Production of monoclonal immunoglobulin M was detected only slightly and focally in the tumors. Plasmacytic differentiation as in Waldenström's macroglobulinemia was not seen in any organs except the tumor on the upper hard palate. From these findings, it is speculated that B-cell lymphoma might have developed in the course of macroglobulinemia.

Aged↗

[A case of accessory nerve neurinoma presenting an intracisternal tumor].

A case of neurinoma from the spinal accessory nerve which is located in the cisterna magna is reported. A 54-year-old woman was admitted to the institute in 1990 with complaints of headache, nausea and ataxic gait for several months. Plain CT showed dilation of the lateral ventricles and a mass of lower density in the cisterna magna. The capsule and septa of the mass were enhanced with contrast medium. MRI showed the mass was low intense on T1-weighted images and high intense on T2-weighted images. Gadolinium visualized the mass multicystic. V-P shunt was performed before tumor resection. Through suboccipital craniectomy and C1 laminectomy the tumor was removed. The tumor had a long neck attached to the right spinal accessory nerve and extended to the cisterna magna.

Accessory Nerve↗

[Thymoma associated with progressive systemic sclerosis--a case report].

A 59-year-old man was admitted to hospital with sclerodactyly and high grade fever. He complained of wrist joint pain and swelling of bilateral hands. Despite of administration of non steroid anti-inflammatory drug and steroid the symptoms were progressive and sclerodactyly spreaded to the forearm. Through the results of the laboratory examination, he was diagnosed as progressive systemic sclerosis (PSS). Chest CT scan showed an anterior mediastinal tumor, and histological examination revealed a spindle cell type thymoma with mild lymphocytic infiltration. During hospitalization, the pulse therapy of steroid was administrated. Progressive sclerodactyly and interstitial pneumonia were improved, but stiffness of hand and joint pain was not diminished. In expectation of improvement of the symptoms, mediastinal tumor was removed. Histological diagnosis was thymoma of epitherial type. After surgery, symptoms decreased and at last diminished, dosage of steroid could be tapered.

Humans↗

Stimulatory effects of yeast and mammalian 14-3-3 proteins on the Raf protein kinase.

Intracellular signaling from receptor tyrosine kinases in mammalian cells results in activation of a signal cascade that includes the guanine nucleotide-binding protein Ras and the protein kinases Raf, MEK [mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) kinase], and MAPK. MAPK activation that is dependent on the coupling of Ras and Raf was reconstituted in yeast. Yeast genes were isolated that, when overexpressed, enhanced the function of Raf. One of them is identical to BMH1, which encodes a protein similar to members of the mammalian 14-3-3 family. Bacterially synthesized mammalian 14-3-3 protein stimulated the activity of Raf prepared from yeast cells expressing c-Raf-1. Thus, the 14-3-3 protein may participate in or be required for activation of Raf.

14-3-3 Proteins↗

Synergistic activation by Ras and 14-3-3 protein of a mitogen-activated protein kinase kinase kinase named Ras-dependent extracellular signal-regulated kinase kinase stimulator.

We have identified, in Xenopus oocyte cytosol, a protein kinase named REKS (Ras-dependent extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase kinase (MEK) stimulator), which phosphorylates and activates recombinant ERK2 through recombinant MEK in a recombinant GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-Ras-dependent manner. We show here that this REKS activity is synergistically enhanced by a combination of mammalian recombinant GTP gamma S-KiRas and 14-3-3 protein purified from rat brain. 14-3-3 protein is known to activate tyrosine and tryptophan hydroxylases, to modulate the protein kinase C activity, to stimulate secretion, and to show phospholipase A2 activity per se. 14-3-3 protein did not affect the MEK activity. 14-3-3 protein neither interacted with Ki-Ras nor affected the neurofibromin activity to stimulate the GTPase activity of Ki-Ras under the conditions where the recombinant N-terminal fragment of c-Raf-1 inhibited it. These results suggest that 14-3-3 protein has an additional function in the regulation of the Ras-MEK-ERK cascade pathway through the activation of REKS.

14-3-3 Proteins↗

[The effect of PTA on cerebral vessels in experimental vasospasm: a histopathological study].

Although the percutaneous transluminal angioplasty (PTA) is an useful procedure for the treatment of symptomatic vasospasm after subarachnoid hemorrhage, the morphological changes in spastic intracranial vessels after PTA are not yet clear. The purpose of this study was to evaluate the effects of PTA angiographically and histologically. Chronic cerebral vasospasm was induced by producing a blood clot in the subarachnoid space around the top of internal carotid siphon in Japanese monkey. After angiographic recognition of vasospasm, PTA was carried out with silicone microballoon at 1 atmosphere, 3 times for 10 seconds. Angiography after PTA disclosed significant dilatation at the site of PTA, without any significant dilatation of distal spastic vessels. Papaverine hydrochloride was then infused intra-arterially, which resulted in significant dilatation of distal spastic vessels. Upon histological examination, deformation and some denudation of endothelial cells were noted in the intimal layer. At the site of denudation, attachment of platelets was observed despite generalized heparinization. Internal elastic lamina and the media were also stretched and myocytes were deformed and arranged irregularly. These changes were not uniform all over the vascular walls. We conclude that the prolonged effect of PTA may be caused by mechanical damage of endothelial cells and myocytes, and the nonuniformity of histological changes in vascular wall may be a leading cause of its rupture during PTA.

Angioplasty, Balloon↗

Developmental changes in the response of rat isolated duodenum to nicotine.

Developmental changes in the response to ganglionic stimulants, nicotine and dimethylphenylpiperazinium, were investigated in rat isolated duodenum by recording isotonic mechanical activity. The duodenal response to nicotine/dimethylphenylpiperazinium (3 x 10(-7) to 10(-3) M) in neonatal rats was contraction, which was blocked by hexamethonium, tetrodotoxin and hyoscine. The response to nicotine/dimethylphenylpiperazinium (10(-6) to 10(-4) M) in the adult duodenum was relaxation, which was blocked by tetrodotoxin and hexamethonium, but by neither guanethidine nor hyoscine. The transition of the response to nicotine/dimethylphenylpiperazinium from contraction to relaxation occurred at around the 3rd postnatal week. Nicotine-induced relaxation of adult duodenum was significantly inhibited by preincubation with alpha-chymotrypsin, a proteolytic enzyme, and a combination of nucleotide pyrophosphatase and 8-phenyltheophylline, a P1 purinoceptor antagonist. Nicotine-induced relaxation was desensitized by alpha, beta-methylene ATP, a stable P2x purinoceptor agonist. These results suggest that the contractile response of isolated duodenum to nicotine is mediated through cholinergic transmission in neonatal rats and the relaxant response is mediated through non-adrenergic, non-cholinergic transmission, which involves both peptidergic and purinergic transmission, in adult rats.

Adenosine Triphosphate↗

Possible involvement of L-arginine-nitric oxide pathway in modulating regional blood flow to brown adipose tissue of rats.

To evaluate whether the L-arginine-nitric oxide (NO) pathway is involved in the regulation of regional blood flow to brown adipose tissue (BAT), the effects of two specific NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), on the blood flow to interscapular brown adipose tissue (IBAT) were studied in urethane-anesthetized rats. Regional blood flow in IBAT was measured with laser-Doppler flowmetry. An intravenous injection of L-NAME and L-NMMA, but not of either D-enantiomer, caused a transient and dose-dependent increase in IBAT blood flow. Dose-response curves for these NO synthase inhibitors showed that L-NAME was more potent than L-NMMA in increasing IBAT blood flow. We also observed a concomitant pressor effect accompanied by a slight decrease in heart rate following intravenous injection of L-NAME and L-NMMA. An elevation of IBAT blood flow and blood pressure induced by both L-NAME and L-NMMA was reversed by L-arginine in an enantiomerically specific manner. The increase in IBAT blood flow induced by NO synthase inhibitors was of shorter duration and less sensitive to L-arginine than the increase in blood pressure. Our results show that the IBAT blood flow is increased by inhibition of NO synthase and that the response of IBAT vasculature to NO synthase inhibitors is different from that of the resistance vessels which regulate blood pressure. The involvement of L-arginine-NO pathways in modulating microcirculation in IBAT is suggested.

Adipose Tissue, Brown↗

Possible role of nitric oxide in 5-hydroxytryptamine-induced increase in vascular permeability in mouse skin.

In order to test the hypothesis that a 5-hydroxytryptamine (5-HT)-induced increase in vascular permeability results from a cascade triggered by activation of the synthesis of nitric oxide (NO), the vascular permeability was investigated using the Pontamine sky blue leakage method in male mice. Subcutaneous injection of 5-HT induced a dose-related increase of vascular permeability at the injection site. The vascular permeability induced by 5-HT was inhibited by pretreatment with intraperitoneal injection of ketanserin (5-HT2A antagonist) and methysergide (5-HT1/2A antagonist), less efficiently by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine (NAN-190) (5-HT1A antagonist), but not by granisetron (5-HT3 antagonist). Increase in vascular permeability induced by 5-HT was inhibited by concurrent intravenous administration of NO synthase inhibitors NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue but not by the inactive enantiomer NG-nitro-D-arginine methyl ester (D-NAME). These results suggest that 5-HT increases vascular permeability by activating the 5-HT receptors and that endogenous NO is involved in this effect of 5-HT.

Amino Acid Oxidoreductases↗

Intra-arterial chemotherapy for brain stem glioma: report of four cases.

Four patients with pontine gliomas were treated with radiation and intra-arterial chemotherapy using ACNU, cisplatin, and/or carboplatin. All underwent biopsy and were histologically proven to have gliomas. Even though three were benign histologically, all appeared malignant on neuroimaging. Two patients had complete remissions; the others had partial responses; three patients died, 36, 14, and 15 months after the primary diagnosis. One patient, now in complete remission, has been alive for 24 months. There was no neurotoxicity except for transient nausea and vomiting. Intra-arterial chemotherapy is effective against brain stem gliomas, producing remission with minimum side effects.

Adolescent↗

Involvement of endogenous nitric oxide in non-adrenergic, non-cholinergic contraction elicited by [Met5]-enkephalin in rat isolated duodenum.

To investigate the possible neuromodulatory role of nitric oxide (NO) in the gastrointestinal tract, an examination was made of the effects of NG-nitro-L-arginine (L-NOARG), an inhibitor of NO synthase, on the intestinal response to [Met5]-enkephalin (ENK) by recording the mechanical activity of the isolated duodenum from rats. [Met5]-enkephalin elicited a biphasic response of the duodenum, i.e. transient relaxation followed by contraction. The relaxation induced by ENK was blocked by naloxone, an opioid receptor antagonist, but not by tetrodotoxin (TTX). The contractile response of the duodenum to ENK was blocked by TTX but not by naloxone. The contractile response was not affected by hyoscine, a muscarinic antagonist, or guanethidine, an adrenergic neuron blocking agent, indicating mediation by non-adrenergic, non-cholinergic (NANC) nerves. The contractile but not the relaxant response to ENK was blocked by L- but not D-NOARG. The contractile response was also inhibited by methylene blue, an inhibitor of both NO synthase and guanylate cyclase, and by indomethacin, a cyclooxygenase inhibitor. Thus, endogenous NO and prostaglandins are involved in the contractile response to ENK. Endogenous NO may modulate the release of excitatory NANC transmitters via a prejunctional mechanism.

Amino Acid Oxidoreductases↗

New teleocidin-related metabolites, (-)-7-geranylindolactam V and blastmycetin F, from Streptoverticillium blastmyceticum.

Two new teleocidin-related metabolites, (-)-7-geranylindolactam-V [2] and blastmycetin F [3], were isolated from fermentation broths of the actinomycete Streptoverticillium blastmyceticum NA34-17, and their structures were determined by spectroscopic methods. Compound 2 bound strongly to phorbol ester receptors in a mouse epidermal particulate fraction, suggesting that it is a potent in vivo tumor promoter comparable to teleocidins A-1 [4] and B-4 [5].

Animals↗

Lack of correlation of hypotensive effects with prevention of cardiac hypertrophy by perindopril after ligation of rat coronary artery.

1. The present study was designed to test the hypothesis that beneficial effects of angiotensin converting enzyme (ACE)inhibitors are independent of a fall in blood pressure in rat experimental heart failure following coronary ligation. 2. The animals were assigned randomly to six groups; sham operation, controls subjected to coronary ligation (control), coronary ligation plus chronic treatment with ACE inhibitors at non- and hypotensive doses; perindopril (0.2 or 2 mg kg-1 day-1) or enalapril (2 or 20 mg kg-1 day-1) for three weeks starting one week after the ligation. 3. Systemic blood pressure was measured every week during the experiments. At the end of the treatments, cardiac function and heart weight (an index of myocardial hypertrophy) were determined. In the other animals, ACE activities in plasma and tissues including heart, kidney, lung and blood vessels were measured. 4. In the controls, cardiac ACE activity, weight of right ventricle and left ventricular end-diastolic pressure (LVEDP) were higher compared to those in the sham-operated animals four weeks after the coronary ligation. However, ACE activities were not changed in plasma, kidney, lung and aorta by ligation of the coronary artery. 5. The chronic treatment with perindopril at a dose of 0.2 mg kg-1 day-1 inhibited the increase in ACE activity in cardiac tissue and suppressed the right ventricular hypertrophy without affecting systemic haemodynamics. In contrast, enalapril at a dose of 20 mg kg-1 day-1, but not 2 mg kg-1 day-1, prevented the development of the right ventricular hypertrophy. Enalapril at 20 mg kg-1 day-1 also lowered systemic blood pressure. 6. There is no significant correlation between systemic blood pressure and right ventricular hypertrophy at the end of the treatment with perindopril (r = 0.06) or enalapril (r = 0.1).7. These findings demonstrate that perindopril, an ACE inhibitor, prevents cardiac hypertrophy without affecting systemic blood pressure in the rat with heart failure after coronary ligation, and suggest that selective augmentation of ACE activity in cardiac tissue is involved in the progression of hypertrophy in this model.

Angiotensin-Converting Enzyme Inhibitors↗

The yeast MOT2 gene encodes a putative zinc finger protein that serves as a global negative regulator affecting expression of several categories of genes, including mating-pheromone-responsive genes.

The STE4 gene encodes the beta subunit of a heterotrimeric G protein that is an essential component of the pheromone signal transduction pathway. To identify downstream component(s) of Ste4, we sought pseudo-revertants that restored mating competence to ste4 mutants. The suppressor mot2 was isolated as a recessive mutation that restored conjugational competence to a temperature-sensitive ste4 mutant and simultaneously conferred a temperature-sensitive growth phenotype. The MOT2 gene encodes a putative zinc finger protein, the deletion of which resulted in temperature-sensitive growth, increased expression of FUS1 in the absence of pheromones, and suppression of a deletion of the alpha-factor receptor. On the other hand, sterility resulting from deletion of STE4 was not suppressed by the mot2 deletion. These phenotypes are similar to those associated with temperature-sensitive mutations in CDC36 and CDC39, which are proposed to encode general negative regulators of transcription rather than factors involved in the pheromone response pathway. Deletion of MOT2 also caused increased transcription of unrelated genes such as GAL7 and PHO84. Overexpression of MOT2 suppresses the growth defect of temperature-sensitive mutations in CDC36 and CDC39. These observations suggest that Mot2 functions as a general negative regulator of transcription in the same processes as Cdc36 and Cdc39.

Amino Acid Sequence↗

Cerebral hemodynamics in hypertensive patients compared with normotensive volunteers. A transcranial Doppler study.

BACKGROUND AND PURPOSE: The present study was designed to examine cerebral hemodynamics in early and chronic stages of hypertension using transcranial Doppler sonography. METHODS: Our study population consisted of 16 chronic hypertensive patients with chronic and small deep brain infarction, 10 young early-stage hypertensive subjects, and 16 young normotensive healthy volunteers. Using three-dimensional mapping techniques, we identified the M1 portion of the middle cerebral arteries and measured mean blood flow velocity, and we calculated the Gosling pulsatility index (PI), Fourier PI of the first harmonic (Fourier PI1), and cerebrovascular resistance. RESULTS: Mean blood flow velocity in the young hypertensive group was statistically higher (71.7 +/- 11.7 cm/s [mean +/- SD]) than among chronic hypertensive subjects (56.9 +/- 21.4 cm/s, P < .01) and normotensive subjects (63.2 +/- 11.8 cm/s, P < .05). Gosling PI presented a mirror image of mean blood flow velocity in both hypertensive and normotensive subjects. Chronic hypertensive subjects showed significantly higher Fourier PI1 (0.32 +/- 0.05) and cerebrovascular resistance (2.08 +/- 0.82 mm Hg/cm per second) than normotensive subjects (0.25 +/- 0.03 and 1.31 +/- 0.23 mm Hg/cm per second [P < .005], respectively) or early-stage hypertensive subjects (0.25 +/- 0.04 and 1.44 +/- 0.26 mm Hg/cm per second [P < .02], respectively). CONCLUSIONS: Early-stage hypertensive subjects demonstrated higher velocity, normal Fourier PI1, and near normal vascular resistance, whereas chronic hypertensive subjects showed near normal velocity, higher Fourier PI, and greater vascular resistance. Results may indicate different degrees of cerebral arteriopathy and arteriolopathy between early and late stages of hypertension.

Adult↗

Multiple brain infarction and hemorrhage by nonbacterial thrombotic endocarditis in occult lung cancer--a case report.

A fifty-four-year-old woman died from multiple brain infarction and hemorrhage in the bilateral cerebrum, cerebellum, and brainstem, with renal infarction. She developed hematuria and transient blindness sixteen days before admission. Low-grade fever, heart murmur, and aortic valve vegetation on ultrasonic cardiography suggested infectious endocarditis. Autopsy study revealed occult adenocarcinoma in the lung and nonbacterial thrombotic endocarditis, but infective endocarditis was not histologically confirmed. The patient was considered to be a rare case of nonbacterial thrombotic endocarditis who developed multiple small infarctions mainly in the brainstem and cerebellum. Nonbacterial thrombotic endocarditis seems to be still an important disease as the embolic source, even if cryptic, of systemic thromboembolism.

Adenocarcinoma↗

Tissue-targeting ability of saccharide-poly(L-lysine) conjugates.

To evaluate the effect of introducing a saccharide moiety to poly(amino acids) on tissue distribution, several glycoconjugates of epsilon-(2-methoxyethoxyacetyl)-poly(L-lysine) of three molecular weights were synthesized using an octylene spacer between the sugar and polymer chain. Methoxyethoxyacetylation of the epsilon-amino group of the lysine unit in poly(L-lysine) was useful for avoiding nonspecific distribution to many tissues as the result of cationic charges. The tissue-targeting ability of each saccharide moiety was considered as the actual amount changed in each tissue caused by saccharide modification. Galactose terminated saccharides such as galactose, lactose and N-acetylgalactosamine accumulated exclusively in the liver, probably by the hepatic receptor. These conjugates could therefore be good carriers for a drug delivery system to the liver. On the other hand, the mannosyl and fucosyl conjugates were preferentially delivered to the reticuloendothelial systems such as those in the liver, spleen and bone marrow. In particular, fucosyl conjugates accumulated more in the bone marrow than in the spleen. Xylosyl conjugates accumulated mostly in the liver and lung. Generally, the accumulated amount in the target tissue increased with increasing molecular weight and an increased number of saccharides on one molecule of polymer.

Animals↗