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Biomedical subjects

Y Fukumoto

Publications and source records attributed to Y Fukumoto.

At least 73 records · Page 4Linked to original sources
PubMed1996

Characterization of ficolins as novel elastin-binding proteins and molecular cloning of human ficolin-1.

A novel elastin-binding protein, EBP-37, was recently identified and purified from human plasma. Its partial amino acid sequences showed significant homology to porcine ficolins, which were originally purified from porcine uterus membranes as multimeric proteins with fibrinogen- and collagen-like domains. Here we report the presence of ficolins in an elastin-binding fraction of porcine plasma and the direct binding of recombinant porcine ficolin-alpha to elastin. In addition, a cDNA encoding a human counterpart of porcine ficolins that is composed of 319 amino acids and is different from EBP-37 was cloned and named human ficolin-1. Northern blotting of various human tissues revealed that human ficolin-1 mRNA is highly expressed in peripheral blood leukocytes. These data suggested that there are at least two kinds of ficolin-related proteins in both pig and human, and they may function as plasma proteins with elastin-binding activities.

Amino Acid Sequence↗
PubMed1996

The importance of the hyperpolarizing mechanism increases as the vessel size decreases in endothelium-dependent relaxations in rat mesenteric circulation.

Endothelium-dependent relaxations are achieved by a combination of endothelium-derived prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). However, it remains to be fully clarified whether the relative contribution of these three mechanisms to endothelium-dependent relaxations varies as a function of the vessel size. This study was designed to clarify this point. Acetylcholine (ACh)-induced endothelium-dependent relaxations were examined in isolated blood vessels taken from the aorta and the proximal and distal mesenteric arteries of the rat. The contributions of PGI2, NO, and EDHF were evaluated by the inhibitory effects of indomethacin, N omega-nitro-L-arginine methyl ester (L-NAME) in the presence of indomethacin, and KCl in the presence of indomethacin and L-NAME, respectively. The membrane potentials were recorded with microelectrodes. The expression of endothelial No synthase (eNOS) was examined by both immunostaining and immunoblotting. The contribution of PGI2 was negligible in three different-sized blood vessels. The contribution of NO was most prominent in the aorta, whereas that of EDHF was most prominent in the distal mesenteric arteries. The resting membrane potential was significantly deeper and the ACh-induced hyperpolarization was greater in the distal mesenteric arteries than those in the aorta. The expression of eNOS was the highest in the aorta and the lowest in the distal mesenteric arteries. These results indicate that the importance of EDHF increases as the vessel size decreases in endothelium-dependent relaxations in the rat mesenteric circulation.

Acetylcholine↗
PubMed1996

Portal vein obstruction accompanied by intrahepatic stones.

This study was conducted to clarify the pathogenesis of portal vein obstruction (PVO) associated with intrahepatic stones. Five cases with PVO and intrahepatic stones were studied retrospectively. The coincidence rate of PVO in intrahepatic stones was 5.8% (5 of 86 cases), and that of intrahepatic stones in PVO, 45.5% (5 of 11 cases). All cases had one or more symptoms of cholangitis, such as high-grade fever, abdominal pain, and jaundice prior to diagnosis of PVO. The portal vein was occluded at the main trunk in 4 and in the left branch in 1. Intrahepatic stones were found in bilateral hepatic lobes in 3 and in the left lobe in 2. Numerous calcium bilirubinate stones were packed in dilatated intrahepatic bile ducts of an excised specimen of the liver. Microscopically, arterial structures could be seen, but the portal vein ceased to be evident about the involved bile duct. Based on the results of this study, persistent cholangitis and packed gallstones were concluded essential to the development of PVO accompanied by intrahepatic stones.

Adult↗
PubMed1996

[Localized cardiac uptake defect with 123I-MIBG SPECT in a case with pure progressive autonomic failure].

A 60-year-old man with 3 years' history of autonomic nervous system disturbances such as orthostatic hypotension, anhidrosis and atonic bladder is presented. He had an episode of paroxysmal atrial fibrillation as well. He had neither extrapyramidal nor cerebellar signs, and was diagnosed as having pure progressive autonomic failure. His cardiac SPECT with 123I-MIBG showed the loss of uptake at the apex and the inferior wall and the diminished uptake at lateral walls. But 99mTc-tetrofosmin SPECT following an exercise stress showed a normal cardiac uptake. It was suggested that non-cardiac disease-associated postganglionic sympathetic fiber abnormality began from an inferior wall and would extend to a whole heart in this disease. The cardiac 123I-MIBG SPECT is thought to be useful for localizing the denervated area of cardiac sympathetic nervous system.

3-Iodobenzylguanidine↗
PubMed1996

The role of fibroblast growth factor-2 in the vascular effects of interleukin-1 beta in porcine coronary arteries in vivo.

OBJECTIVE: We recently demonstrated that chronic treatment with interleukin-1 beta (IL-1 beta), a major inflammatory cytokine found in atherosclerotic lesions, induces coronary arteriosclerotic changes and vasospastic responses to serotonin and histamine in pigs in vivo and that those responses are partially mediated by platelet-derived growth factor (PDGF). This study was designed to examine, first, whether the effects of IL-1 beta are also partially mediated by fibroblast growth factor-2 (FGF-2), which is another important growth factor in atherosclerotic lesions, and, secondly, whether chronic treatment with FGF-2 per se also induces histological and functional changes in porcine coronary arteries in vivo. METHODS: Porcine coronary arteries were aseptically wrapped with cotton mesh absorbing IL-1 beta with or without neutralizing antibody to FGF-2. In a separate series of experiments porcine coronary arteries were chronically treated with FGF-2 itself in the same manner. Coronary vascular responses in vivo and histological changes were examined 2 weeks after the operation. RESULTS: Coronary vasospastic responses to serotonin and histamine and neointimal formation were induced at the site of the coronary artery where IL-1 beta was chronically and locally applied. These responses were significantly suppressed by co-treatment with a neutralizing antibody to FGF-2 but not by that with non-immune IgG. Immunostaining revealed the presence of FGF-2 in the endothelial cells, the thickened intima and the media at the IL-1 beta-treated site. Furthermore, chronic treatment with FGF-2 also induced coronary vasospastic responses to serotonin and histamine and neointimal formation. CONCLUSIONS: These results suggest that the vascular effects of IL-1 beta may also be mediated by FGF-2 in our swine model and that chronic treatment with FGF-2 also causes coronary arteriosclerotic changes and vasospastic responses in vivo.

Animals↗
PubMed1995

Enhancement of muscarinic receptor-coupled phosphatidyl inositol hydrolysis in diabetic bladder.

We previously have shown an increase in muscarinic receptor density in streptozotocin (STZ)-induced diabetic and sucrose-fed diuretic rat detrusor that correlates with an increase in the contractile response to muscarinic agonist (J Pharmacol Exp Ther 248:81, 1989; Diabetes 40: 265, 1991). To investigate the signal transduction pathway involved in this altered functional response, we examined muscarinic receptor-coupled phosphatidylinositol metabolism in STZ-diabetic, sucrose-fed diuretic and age-matched control rat bladders. [3H]myo-inositol uptake was similar in all groups, but incorporation of myo-inositol into phosphatidylinositol (PI) was significantly increased in the diabetic bladder compared to the sucrose-fed and control rat bladders. Carbachol-induced increase in inositol phosphate (IPs) production was higher in the diabetic bladder than in bladders from control and sucrose-fed animals although the EC50 values were similar for all groups. Enhanced inositol phosphate production after muscarinic agonist stimulation may be due not only to the upregulation of muscarinic receptors but also the increased incorporation of myo-inositol into PI in the STZ-induced diabetic bladder.

Animals↗
PubMed1995

Chronic inhibition of endothelium-derived nitric oxide synthesis causes coronary microvascular structural changes and hyperreactivity to serotonin in pigs.

BACKGROUND: Endothelium-derived nitric oxide (NO) is believed to regulate myocardial perfusion and structural changes in the vascular wall. Our objective was to determine whether chronic inhibition of NO synthesis causes structural and functional changes in coronary arteries. METHODS AND RESULTS: Coronary vasomotor response was studied in pigs before and after chronic oral administration of the NO synthesis antagonist N omega-nitro-L-arginine methyl ester (L-NAME) 30 mg.kg-1.d-1 for 2 weeks. Chronic L-NAME treatment increased (P < .01) arterial pressure but did not alter baseline coronary blood flow (CBF), epicardial coronary diameter, or heart rate. Chronic L-NAME treatment augmented (P < .01) the decrease in CBF in response to intracoronary serotonin (30 micrograms/kg) from 5 +/- 14% to 40 +/- 5% but did not alter the CBF response to prostaglandin F2 alpha. The serotonin-induced decrease in CBF after acute L-NAME administration was still less before (1.3 +/- 0.4%) than after chronic L-NAME treatment (51 +/- 6%). Chronic L-NAME treatment attenuated the increase in CBF with bradykinin (100 ng/kg) but did not alter the CBF response to nitroglycerin (10 micrograms/kg). Compared with intact pigs without L-NAME treatment, L-NAME-treated pigs had significant thickening of the media in the microvessels (diameter, < 300 microns) but not in the large epicardial vessels. Chronic intracoronary infusion of L-NAME at 3 mg.kg-1.d-1 for 2 weeks, which did not produce arterial hypertension, caused similar microvascular medial thickening. CONCLUSIONS: These results indicate that chronic administration of L-NAME caused coronary microvascular structural changes and hyperreactivity to serotonin in pigs in vivo, suggesting an important role of defective NO synthesis in coronary microvascular disorders.

Animals↗
PubMed1995

[A case of polyglandular autoimmune syndrome (PGA) type 1 complicated with slowly progressive IDDM].

A case of an 18-year-old female with polyglandular autoimmune syndrome (PGA) type 1 complicated by slowly progressive IDDM was described. She had epilepsy at the age of 5, and mucocutaneous candidiasis and hypoparathyroidism at 7 years. At the age of 18, the patient noticed thirst and body weight loss. On admission, she had uneven teeth and chronic mucocutaneous candidiasis. Plasma blood glucose was 312 mg/dl without ketosis, hemoglobin Alc 9.1%, serum calcium 3.5 mEq/l, serum phosphorus 6.0 mg/dl. A CT scan of her brain revealed calcification in the bilateral basal ganglia. Serum intact PTH was less than 10 pg/ml. Ellsworth-Howard's test showed hyperresponsiveness in the secretion of urinary phosphorus and cyclic-AMP. Other endocrinological studies showed no abnormality except for mild hyporesponsiveness in the secretion of urinary C-peptide (39.6 mu g/day). After admission, she was initially treated with diet alone with positive islet cell antibody (ICA). Three months later she was treated with low dose insulin, and ICA became negative. Then 5 months later it became positive again. Sixteen months later she had IDDM with positive ICA and without the secretion of urinary C-peptide. On the basis of these results, we diagnosed this case as PGA type 1 with the manifestations of hypoparathyroidism, chronic mucocutaneous candidiasis and slowly progressive IDDM. This is the second case report in Japan about PGA type 1. Furthermore, this case demonstrates for the first time in Japan that slowly progressive IDDM is complicated by PGA type 1. The patient had this HLA typing: A 24(9), BW52(5), BW60(40), CW3, DR2, DRW12, DQW7. More investigation is necessary to clarify the mechanism of PGA type 1.

Adolescent↗
PubMed1995

Regional differences in the density and subtype specificity of endothelin receptors in rabbit urinary tract.

We investigated the binding characteristics of endothelin (ET) receptors in rabbit ureter, bladder dome, bladder base, and urethra and compared the observed receptor properties with those of cloned human ETA and ETB receptors expressed in Chinese hamster ovary K-1 (CHO) cells. Receptor binding experiments with [125I]ET-1 revealed the presence of a single class of specific, saturable, high affinity [125I]ET-1 binding sites in all of the regions of the studied urinary tract. The rank order of the densities (Bmax values) of [125I]ET-1 binding sites was: ureter "bladder dome > bladder base = urethra. ET-1 and ET-2 inhibited [125I]ET-1 binding to the membrane particulates from the various regions of the urinary tract with single high affinity constants. A selective ETA receptor antagonist, BQ 123, and selective ETB agonists, ET-3 and sarafotoxin S6c (STXc), inhibited [125I]ET-1 binding to bladder dome, bladder base, and urethra with high and low affinity constants indicating the presence of both ETA and ETB receptor subtypes in these tissues. The subtype specificity of ET receptors in the rabbit tissues is confirmed with inhibition data obtained from similar binding studies in cloned human ETA and ETB receptors. The proportions of high affinity binding sites for ET-3, representing ETB receptors, were approximately 25%, 27%, and 46% in bladder dome, bladder base, and urethra, respectively. Corresponding values for STXc were approximately 17%, 28%, and 43% in bladder dome, bladder base, and urethra, respectively. In contrast to the findings for ET-3 and STXc, the proportions of high affinity binding sites for BQ 123, representing ETA receptors, in bladder dome, bladder base, and urethra were approximately 84%, 74%, and 60%, respectively. In ureter, these selective compounds inhibited [125I]ET-1 binding with either a low (ET-3 and STXc) or a high binding affinity (BQ 123), suggesting the presence of only a single receptor subtype (ETA) in this tissue. These data indicate that there are regional differences in the density and subtype specificity of ET receptors in the rabbit urinary tract.

Animals↗
PubMed1995

Acute tubulointerstitial nephritis in association with Yersinia pseudotuberculosis infection.

A 4-year-old girl was diagnosed as having acute renal failure due to tubulointerstitial nephritis. The girl presented with remittent fever, vomiting and non-oliguric acute renal failure with sterile pyuria and tubular reabsorptive dysfunction. Ultrasound examination revealed that the kidneys were markedly enlarged with diffuse hyperechogenicity in the cortex when the abnormal renal function was present and were restored in size and echogenicity when the renal function normalised. A diagnosis of Yersinia pseudotuberculosis infection was based on a rise in haemagglutination titres against the organism.

Acute Disease↗
PubMed1995

Oval pupil in patients with diabetes mellitus: examination by measurement of the dark-adapted pupillary area and pupillary light reflex.

Determination of the dark-adapted pupillary area (DAPA) by infrared photography revealed that some diabetic patients show corectopia (oval pupil) in addition to the small DAPA as pupillary abnormalities. The prevalence and clinical details of oval pupil were compared between diabetic patients and healthy subjects. Pupillary light reflexes were also analyzed with an infrared videopupillography in some of the diabetic patients. The healthy subjects were examined for the influence of age on the ratio of the pupillary diameter of the major and minor axes. The ratio was 1.04 +/- 0.02 (mean +/- S.D.) in the healthy subjects, and cases in which the ratio was +2 S.D. or higher than the mean ratio were defined as oval pupil. Oval pupil was observed in 21 (24%) of 86 diabetic patients, and was correlated with heart rate variation (P < 0.05) and DAPA (P < 0.01), which represent an autonomic dysfunction. Quantitative analysis of pupillary light reflexes with an infrared videopupillography revealed that the dark-adapted pupillary area before photic stimulation (P < 0.01) and the maximum %-velocity of constriction (P < 0.05) were significantly less in the oval pupil group than in the round pupil group. Cranial magnetic resonance imaging revealed no abnormalities in the oval pupil group. From these results, a peripheral autonomic disorder was implicated in the etiology of oval pupils in diabetic patients.

Adult↗
PubMed1995

EBP-37, a new elastin-binding protein in human plasma: structural similarity to ficolins, transforming growth factor-beta 1-binding proteins.

In order to study the elastin-binding factors in blood, human plasma was applied to an alpha-elastin-Sepharose column. The column-binding fraction contained a 37-kDa protein, which was tentatively named EBP-37. Partial amino acid sequences of EBP-37 were determined. It had collagenous and non-collagenous domains. Homology searches of the sequences revealed that the protein is very similar but not identical to ficolins, transforming growth factor-beta 1 (TGF-beta 1)-binding proteins from porcine uterus membranes. Direct interaction of EBP-37 with elastin was confirmed by demonstrating the binding of the isolated EBP-37 to alpha-elastin on a nitrocellulose membrane using the EBP-37-specific antiserum. The existence of oligomers and multimers crosslinked by disulfide bonds was demonstrated by immunoblot analysis. Possible functions of EBP-37 are discussed.

Amino Acid Sequence↗
PubMed1995

Tyrosine kinase inhibitor suppresses coronary arteriosclerotic changes and vasospastic responses induced by chronic treatment with interleukin-1 beta in pigs in vivo.

We recently demonstrated that chronic treatment with IL-1 beta induces coronary arteriosclerotic changes and vasospastic responses to autacoids in pigs in vivo and that those responses are importantly mediated by PDGF. The receptors for PDGF and other major growth factors are known to have tyrosine kinase activity. We therefore investigated the effects of a selective tyrosine kinase inhibitor, ST 638, on those responses induced by IL-1 beta in our swine model. Intimal thickening and coronary vasospastic responses to serotonin and histamine were induced at the site of the coronary artery where IL-1 beta was chronically and locally applied. These responses were significantly suppressed in a dose-dependent manner by cotreatment with ST 638. In addition, ST 494, which is an inactive form of ST 638, did not inhibit those responses. The treatment with ST 638 alone did not affect the coronary vasoconstricting responses to the autacoids. Immunoblotting using an antibody to phosphotyrosines confirmed the inhibitory effects of ST 638 on the tyrosine phosphorylations induced by IL-1 beta. These results thus suggest that tyrosine kinase activation may play an important role in mediating the effects of IL-1 beta, while also suggesting that ST 638 has an inhibitory effect on the arteriosclerotic changes and vasospastic responses to autacoids in our swine model in vivo.

Animals↗
PubMed1995

[Early relapse after peripheral blood stem cell transplantation in acute myelogenous leukemia with t(8;21)].

We report a 3-year-old boy with acute myelogenous leukemia, who relapsed very early after peripheral blood stem cell transplantation (PBSCT). He was admitted with a tumor in maxillar sinus and hemorrhagic diathesis and was diagnosed as having acute myelogenous leukemia with t(8;21). He achieved complete remission with etoposide, cytosine arabinoside and mitoxantrone. After 8 courses of consolidation therapy and marrow ablative chemotherapy, he received PBSCT. G-CSF was given from day 0 because of severe infection. WBC and platelete counts rapidly increased, however, from day 20 platelet count spontaneously decreased. Concomitantly bone marrow examination revealed the presence of blastic cells. RT-PCR showed that the presence of AML 1/MTG 8 chimera mRNA in the cryopreserved PBSC samples. In vitro analysis also revealed that leukemic cells had G-CSF receptors and increased 3H-thymidine uptake in the presence of G-CSF. These findings strongly suggest that the reinfusion of leukemic cells in PBSC and the administration of G-CSF after PBSCT might be relevant to early relapse in this patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Diabetes-induced alterations in the properties of muscarinic cholinergic receptors in rat vas deferens.

Muscarinic cholinergic receptors were identified and characterized by radioligand receptor binding assay using [3H]quinuclidinyl benzilate (QNB) in rat vas deferens membrane particulates of three experimental groups: 1) 8-week diabetic, 2) 8-week diabetic insulin-treated and 3) age-matched control. Diabetes was induced by the intravenous injection of 65 mg./kg. streptozotocin (STZ). The density of muscarinic receptors (Bmax values), as determined by saturation experiments with [3H]QNB, was demonstrated to be higher in the vas deferens of diabetic rats than in the vas deferens of control and diabetic insulin-treated rats. The equilibrium dissociation constants (KD values), however, were similar in all three groups. Muscarinic cholinergic antagonists competed with [3H]QNB binding sites in the vas deferens membrane particulates with the following rank order of Ki values: atropine < methoctramine < or = 4-DAMP < AF-DX 116 < HHSiD < pirenzepine = pfHHSiD. The pharmacological profile of muscarinic receptors was similar in all three groups. Additional pharmacological studies showed a similar rank order of Ki values for vas deferens, bladder dome and heart, but this rank order was significantly different in cerebral cortex and prostate. This is consistent with the predominance of the M2 muscarinic cholinergic receptor subtype in the rat vas deferens. It is concluded that STZ-induced diabetes causes an upregulation of muscarinic cholinergic receptor density in the rat vas deferens that can be prevented by the administration of insulin.

Animals↗