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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 91 records · Page 5Linked to original sources

Mice lacking histidine decarboxylase exhibit abnormal mast cells.

Histidine decarboxylase (HDC) synthesizes histamine from histidine in mammals. To evaluate the role of histamine, we generated HDC-deficient mice using a gene targeting method. The mice showed a histamine deficiency and lacked histamine-synthesizing activity from histidine. These HDC-deficient mice are viable and fertile but exhibit a decrease in the numbers of mast cells while the remaining mast cells show an altered morphology and reduced granular content. The amounts of mast cell granular proteases were tremendously reduced. The HDC-deficient mice provide a unique and promising model for studying the role of histamine in a broad range of normal and disease processes.

Alleles↗

The charge-transfer complex trans-STB-TCNQF4.

In the crystal structure of the title charge-transfer complex, namely trans-stilbene-2,2'-(2,3,5,6-tetrafluorobenzene-1,4-diylidene)propanedinitrile (1/1) (trans-STB-TCNQF(4)), C(14)H(12).C(12)F(4)N(4), the planar STB and TCNQF(4) molecules are stacked alternately. The structure is not isostructural with that of STB-TCNQ. No anomaly was found in the displacement parameters of any atoms, while the bond length of the central C=C moiety was shorter than the corresponding bond in ethylene. This suggests that the central C=C moiety of the STB molecule vibrates with a large amplitude, similar to the case in free STB and STB-TCNQ.

Journal Article↗

High-fidelity transmission acquired via a developmental decrease in NMDA receptor expression at an auditory synapse.

Central auditory relay synapses in mature animals follow high-frequency inputs for computation of sound localization. In immature mice, however, transmission at the calyx of Held synapse in auditory brainstem was inaccurate for high-frequency inputs because the summed slow synaptic potential components caused aberrant firings or blocked action potentials. As the mice matured, synaptic potentials became shorter, with smaller and faster NMDA receptor components, thereby establishing the precise one-to-one transmission for high-frequency inputs. Developmental acquisition of this high-fidelity transmission could be mimicked experimentally in immature mice by blocking NMDA receptors with d(-)2-amino-5-phosphonovaleric acid (d-APV). Furthermore, bilateral cochlear ablations at postnatal day 7 (P7) attenuated the developmental decrease of NMDA receptor expression and prevented the acquisition of high-fidelity transmission. We suggest that auditory activity, which begins at P10-P12 in mice, downregulates the expression of postsynaptic NMDA receptors, thereby contributing to the establishment of high-fidelity synaptic transmission.

2-Amino-5-phosphonovalerate↗

Ribosomal protein S5 interacts with the internal ribosomal entry site of hepatitis C virus.

Translational initiation of hepatitis C virus (HCV) genome RNA occurs via its highly structured 5' noncoding region called the internal ribosome entry site (IRES). Recent studies indicate that HCV IRES and 40 S ribosomal subunit form a stable binary complex that is believed to be important for the subsequent assembly of the 48 S initiation complex. Ribosomal protein (rp) S9 has been suggested as the prime candidate protein for binding of the HCV IRES to the 40 S subunit. RpS9 has a molecular mass of approximately 25 kDa in UV cross-linking experiments. In the present study, we examined the approximately 25-kDa proteins of the 40 S ribosome that form complexes with the HCV IRES upon UV cross-linking. Immunoprecipitation with specific antibodies against two 25-kDa 40 S proteins, rpS5 and rpS9, clearly identified rpS5 as the protein bound to the IRES. Thus, our results support rpS5 as the critical element in positioning the HCV RNA on the 40 S ribosomal subunit during translation initiation.

5' Untranslated Regions↗

Initial and long-term results of directional coronary atherectomy in unprotected left main coronary artery.

Angioplasty in the unprotected left main coronary artery (LMCA) has been controversial. Recently, several studies have suggested that new procedures and devices such as directional coronary atherectomy (DCA) and stents may change this situation. Although there are many reports of unprotected LMCA stenting, there are few reports of DCA of this lesion. Therefore, initial and long-term results were evaluated in 101 patients who underwent DCA for unprotected LMCA in our hospital. Emergency procedures were performed in 15 patients and electively in 86 patients. Scheduled angiographic follow-up was routinely performed, and all patients were clinically followed for >4 months after DCA. Technical success was achieved in 99%, and in-hospital outcomes were cardiac death (2%), noncardiac death (4%), Q-wave myocardial infarction (1%), non-Q-wave myocardial infarction (8.9%), coronary artery bypass grafting (0%), and repeat angioplasty (4%). In-hospital results varied considerably, depending on presentation. In-hospital mortality was significantly higher in the emergency, left ventricular ejection fraction < or =35%, and high-risk surgical subgroups. The angiographic restenosis rate was 20.4% at follow-up, and its predictor was postminimal lumen diameter by multivariate analysis. Mean clinical follow-up was 2.8 years; estimated 1- and 3-year survival rates were 87% and 80.7%, respectively. The cardiac survival rate of the low-risk surgical subgroup was significantly higher than that of the high-risk surgical subgroup (p <0.05). Thus, our data show that DCA can be performed safely and effectively in unprotected LMCA with an acceptable low restenosis rate and high survival rate.

Adult↗

Novel functions of complex carbohydrates elucidated by the mutant mice of glycosyltransferase genes.

Complex carbohydrates consist of carbohydrate moieties and protein or lipid portions, resulting in the formation of glycoproteins, proteoglycans or glycosphingolipids. The polymorphic carbohydrate structures are believed to contain profound biological implications which are important in cell-cell or cell-extracellular matrix interactions. A number of studies to delineate the roles of carbohydrates have been performed, and demonstrated definite changes in their profiles, cellular phenotypic changes or, sometimes, morphological and functional changes in tissues after modification of their structures. Recent successes in the isolation of glycosyltransferase genes and their modification enzyme genes has enabled clearer demonstrations of the roles of complex carbohydrates. In particular, genetic modification of glycosyltransferase genes in mice can elucidate the biological significances of their products in vivo. Here, we summarize recent advances in the understanding of the roles of complex carbohydrates provided from studies of gene knock-out mice of glycosyltransferase and modification enzyme genes focusing on novel functions which had not been expected.

Animals↗

Adenosine receptor subtypes modulate two major functional pathways for hippocampal serotonin release.

To clarify the mechanisms of interaction between adenosine A(1) receptor (A1-R) and adenosine A(2) receptor (A2-R) on neurotransmitter release, this study determined the functional interactions among adenosine receptors (AD-Rs), voltage-sensitive Ca(2+) channels (VSCCs), protein kinases (PKs), and synaptic proteins [N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors] on hippocampal serotonin release using in vivo microdialysis in freely moving rat. Basal serotonin release was regulated by two functional complexes: N-type VSCC (N-VSCC)/calcium-phospholipid-dependent protein kinase (PKC)/syntaxin (major pathway) and P-type VSCC (P-VSCC)/cyclic AMP-dependent protein kinase (PKA)/synaptobrevin (minor pathway). However, K(+)-evoked serotonin release was regulated by N-VSCC/PKC/syntaxin (minor pathway) and P-VSCC/PKA/synaptobrevin (major pathway). A1-R antagonists increased basal serotonin release, which was reduced by inhibitors of N-VSCC, PKC, and syntaxin predominantly and by inhibitors of PKA and synaptobrevin weakly, but was not affected by P-VSCC inhibitor. In the presence of A1-R antagonist, A2-R agonists increased basal serotonin release, which was inhibited by inhibitors of P-VSCC, PKA, and synaptobrevin predominantly and reduced by inhibitors of N-VSCC, PKC, and syntaxin weakly. Under the condition of activation of adenylate cyclase in the absence of A1-R antagonists, A2-R agonists increased basal serotonin release. A1-R antagonist and A2-R agonist enhanced K(+)-evoked serotonin release, which was inhibited by inhibitors of P-VSCC, PKA, and synaptobrevin predominantly. These results suggest that an activation of A1-R suppresses serotonin release via inhibition of both N-VSCC/PKC/syntaxin and P-VSCC/PKA/synaptobrevin pathways, and an activation of A2-R stimulates serotonin release via enhancement of the P-VSCC/PKA/synaptobrevin pathway. Therefore, PKA activity plays an important role in the interaction between A1-R and A2-R on hippocampal serotonin release.

Adenylyl Cyclases↗

Dynamic changes in cytokine levels in serum and synovial fluid following filtration leukocytapheresis therapy in patients with rheumatoid arthritis.

We attempted to determine whether various cytokine levels in the serum and synovial fluid (SF) of rheumatoid arthritis (RA) patients are influenced by the performance of filtration leukocytapheresis (LCP). The filtration LCP procedure that used a Cellsorba column (LCP group: n=22; responder subgroup: n=17, non-responder subgroup: n=5) or sham apheresis (control group; n=7) was repeated three times at 1-week intervals. Serum (LCP group, n=22; control group, n=7) and SF (LCP group, n=6; control group, n=3) samples were collected before and after LCP. Levels of tumor necrosis factor alpha (TNFalpha), interleukins (IL-1 beta, IL-2, IL-6, IL-8, IL-10, and IL-15), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), RANTES were measured by an enzyme-linked immunosorbent assay. Serum TNF alpha, IL-15, and RANTES were significantly reduced only in the LCP group. Serum IL-10 significantly increased only in the LCP group. In the LCP subgroup, serum IL-15, GM-CSF, and RANTES levels were reduced significantly, while serum IL-10 levels increased significantly only in the responder group after treatment. Serum TNF alpha levels were reduced significantly in both subgroups. Changes in serum IL-10 correlated positively with the improvement of patient's assessment of pain and global severity, and physician's assessment of global severity. These results indicate that the removal of leukocytes from the peripheral blood of RA patients provokes dynamic changes in some cytokine levels in the serum and/or synovial fluid. These changes may explain some of the mechanisms by which the articular symptoms are improved by filtration LCP.

Adult↗

Direct measurement of HDL cholesterol: method eliminating apolipoprotein E-rich particles.

It has been reported that the existing direct method of high density lipoprotein (HDL) cholesterol measures particles enriched with apolipoprotein E (apoE). The aim of our study was to investigate a new analytical protocol to directly measure HDL cholesterol that eliminates apoE-rich particles. The interactions of four lipoproteins (HDL(3), HDL(2), LDL, and VLDL + chylomicron) with surfactants, divalent cations, sugars, and lectins were investigated. By analyzing sera, HDL(3), and HDL(2), we examined the relationships among the measurements obtained by our protocol, a precipitation method using heparin-MnCl(2), and a commercially available kit for this direct method. A significant difference was found between the direct method and the heparin-MnCl(2) method, but not between our protocol and the heparin-MnCl(2) method. Multiple regression analysis showed that the difference between the direct method and the heparin MnCl(2) method is dependent on sources of apoE-rich HDL. In conclusion, our protocol enables a direct measurement of HDL cholesterol that eliminates apoE-rich particles.

Apolipoproteins E↗

Direct measurement of low-density-lipoprotein cholesterol is more effective than total cholesterol for the purpose of lipoprotein screening.

BACKGROUND: We have developed a new method for chemically measuring blood low-density-lipoprotein (LDL) cholesterol. In the present study, we simulated guidelines of the National Cholesterol Education Program (NCEP) using our LDL cholesterol measurements. METHODS: Blood samples were collected from 1,069 individuals (519 males, 550 females) who were referred to our laboratory at Niigata University Hospital for lipoprotein analysis. LDL cholesterol levels were determined according to our assay protocol, which has been published previously. Subjects were categorized by NCEP guidelines and identified "false positives" and "false negatives" on the basis of LDL cholesterol levels measured by our method. RESULTS: The sensitivity of the NCEP guidelines is 87.5% and the specificity is 87.1%, provided we assume that every individual has fewer than two risk factors for coronary heart disease. If we assume that every individual has two or more risk factors, the sensitivity and specificity of the guidelines are 99 and 56.8%, respectively. CONCLUSION: This study presents an opportunity to reevaluate guidelines for routine lipoprotein screening. The chance that individuals with higher LDL cholesterol and lower high-density-lipoprotein cholesterol levels in serum would be missed at initial classification should be zero. The chance that individuals with desirable lipid levels would undergo further lipoprotein analysis should be decreased. Since the new method can be implemented cost-effectively in routine lipoprotein screening, direct measurement of LDL cholesterol could replace total cholesterol.

Adult↗

Portal vein thrombosis successfully treated with a colectomy in active ulcerative colitis: report of a case.

Portal vein thrombosis is a rare complication in ulcerative colitis. We present a patient with portal vein thrombosis in ulcerative colitis who was successfully treated with colectomy. A 38-year-old Japanese female was admitted to our hospital because of an exacerbation of colitis. Abdominal ultrasonography performed because of liver dysfunction showed the thrombus in an umbilical portion of the portal vein. The patient underwent a subtotal colectomy and ileostomy because her colitis did not respond to intensive intravenous therapy. Although portal vein thrombus was treated with an intravenous infusion of urokinase before the operation, no change in the thrombus size was found. Approximately three months after the colectomy, the thrombus of the portal vein disappeared without anticoagulant therapy. Although a resection of an inflamed colon may be theoretically effective in the thrombosis in the inflammatory bowel disease, its benefit has not been confirmed. Our case suggests that the resection of the diseased bowel may have a favorable effect on the course of portal vein thrombosis in acute attacks of ulcerative colitis.

Adult↗

Mesenteric panniculitis of the colon with obstruction of the inferior mesenteric vein: report of a case.

Mesenteric panniculitis is a rare disease characterized by nonspecific inflammation of the fat tissue of the mesentery. We present an extremely rare case of mesenteric panniculitis of the sigmoid colon, complicated by occlusion of the inferior mesenteric vein. A 75-year-old male presented with a one-month history of abdominal distention and abdominal mass without pain. Physical examination revealed a firm mass in the lower abdomen. Barium enema study demonstrated rugged mucosa and a serrated contour in the rectosigmoid colon. Computed tomography showed that the mass arose from the mesentery, which surrounded the mesenteric vessels. The density of the mass was slightly higher than that of fatty tissue. Based on these radiologic findings, the patient was diagnosed as having mesenteric panniculitis of the rectosigmoid colon. Colonoscopy showed narrowing with edematous mucosa in the rectosigmoid colon, whereas marked dilated vessels were noted in the proximal portion of the sigmoid colon. Angiography showed occlusion of the inferior mesenteric vein, with venous flow returning via a collateral vein. The patient was observed without medication because his condition was satisfactory. His symptoms subsequently disappeared during a period of several weeks. The mass in the lower abdomen gradually diminished in size, disappearing three months later. Computed tomography and barium enema showed improvement of the lesion. The favorable outcome of the present case was probably because of formation of a collateral vein. The present case suggests that aggressive therapy for mesenteric panniculitis should be avoided, because the outcome of this disorder is good, even when there is obstruction of vessels.

Abdominal Pain↗

Nitric oxide inhibits the release of acetylcholine in the isolated retina.

BACKGROUND: Recent studies have revealed that administration of nitric oxide (NO) donors increases the release of neurotransmitters in various brain regions. In the retina, NO synthetase (NOS) is found in retinal amacrine and ganglion cells, and it is evident that NO is involved in encoding visual information. In the present study, therefore, NO donors were used to study the effect of exogenous NO on the high K(+)-evoked release of endogenous acetylcholine (ACh) in the rat retina. METHODS: Isolated rat retinal preparations were superfused with modified Krebs-Ringer bicarbonate buffer solution. In each experiment, stimulation for 10 min with 30 mM KCl was done twice. The amounts of ACh released by the first or second KCl stimulation were termed S1 and S2 respectively. Test agents were applied just before the second KCl stimulation. The effects of test agents were evaluated as S2 divided by S1. ACh was converted to hydrogen peroxide and electrochemically assayed by high-performance liquid chromatography. RESULTS: S-Nitro-N-acetyl-DL-penicillamine (SNAP), an NO donor, dose-dependently inhibited the high K(+)-evoked release of endogenous ACh. Such inhibition by NO was confirmed also by another NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxy imino]-5-nitro-3-hexenamide (NOR3). The inhibitory effect of SNAP was abolished by both carboxy-PTIO, an NO scavenger, and bicuculline, an antagonist of GABAA receptors. CONCLUSIONS: The NO-induced decrease of ACh release is probably due to an NO-induced increase of GABAergic system inhibition.

Acetylcholine↗

Mixed state on a sparsely encoded associative memory model.

We analyzed symmetric mixed states corresponding to the so-called concept formation on a sparsely encoded associative memory model with 0-1 neurons. Three types of mixed states--OR, AND, and a majority decision--are described as typical examples. Each element of the OR mixed state is composed of corresponding memory pattern elements by means of the OR operation. The other two types are similarly defined. By analyzing their equilibrium properties through self-consistent signal-to-noise analysis and computer simulation, we found that the storage capacity of the OR mixed state diverges in a sparse limit, but that the other states do not diverge. In addition, we found that the optimal threshold values, which maximize the storage capacity for the memory pattern and the OR mixed state, coincide with each other in the spare limit. We conclude that the OR mixed state is a reasonable representative of mixed state in the sparse limit.

Computer Simulation↗

Multiple venous aneurysm of a basilic vein.

An uncommon case of multiple venous aneurysm of the basilic vein was diagnosed in a 61-year-old woman who presented with a left arm mass. The lesion was successfully resected with day surgery. Clinical features, including the complications, treatment, and etiology of these exceedingly uncommon lesions, are discussed.

Aneurysm↗

Different recurrence patterns after phototherapeutic keratectomy in the corneal dystrophy resulting from homozygous and heterozygous R124H BIG-H3 mutation.

PURPOSE: To report the recurrence pattern of corneal deposits after phototherapeutic keratectomy in patients with corneal dystrophies resulting from homozygous and heterozygous Arg124His (R124H) mutation of the BIG-H3 gene. METHODS: Slit-lamp examination was performed on patients with corneal dystrophy resulting from a genetically confirmed BIG-H3 R124H mutation. RESULTS: The recurrence of corneal deposits after phototherapeutic keratectomy in patient with heterozygous R124H mutation was mild; the granular opacities occurred as spot lesions in the central cornea. The patient with a homozygous mutation had a more severe pattern, and the recurrent lesions were diffuse and occurred in the periphery between the corneal epithelium and laser-ablated stroma. The recurrence-free interval in homozygous patients was shorter. CONCLUSION: The mutation genotype of BIG-H3 gene determines the recurrence pattern after phototherapeutic keratectomy.

Aged↗

Is segmentectomy with lymph node assessment an alternative to lobectomy for non-small cell lung cancer of 2 cm or smaller?

BACKGROUND: Lesser resection than the standard lobectomy for small-sized cT1N0M0 non-small cell lung cancers continues to be debated. METHODS: We reviewed specimens of 139 patients after lobectomy for cT1N0M0 cancer of 2 cm or less. In addition, we prospectively enrolled 70 patients able to tolerate a lobectomy, in a trial of lesser resection for these lesions. The limited procedure consisted of segmentectomy in which the resection line was delivered beyond the burdened segment, plus exploration of lymph nodes by frozen sectioning. This procedure was modified if the result was positive; this modified procedure was called extended segmentectomy. RESULTS: The nodal status after lobectomy was pN0, 107 patients; pN1, 12 patients; and pN2, 20 patients. Of the pN1 patients, 2 had only intralobar nodal involvement within the same segment of the main tumor. In the remaining 30 patients with nodal involvement, we ascertained the nodal involvement during the operation. Regarding intrapulmonary metastasis, 1 of 8 patients having this metastasis had the lesion at the segment where the main tumor was not located and had N2 disease, which was detected intraoperatively. If extended segmentectomy had been performed instead of lobectomy, the lesion could have been removed completely. The 5-year survival of patients with cT1N0M0 cancer of 2 cm or less was 87.3% after extended segmentectomy. There were no local recurrences and three noncancer-related deaths. Among patients with pT1N0M0 cancer of 2 cm or less, the 5-year survival was 87.1% in the extended segmentectomy group and 87.7% in the lobectomy group (p = 0.8008). CONCLUSIONS: Extended segmentectomy should be considered as an alternative for patients with cT1N0M0 non-small cell lung cancer of 2 cm or smaller.

Carcinoma, Non-Small-Cell Lung↗