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Biomedical subjects

Y Sekiguchi

Publications and source records attributed to Y Sekiguchi.

At least 37 records · Page 2Linked to original sources

Chemical modification of apomorphine to discover sigma ligands: 6H-dibenzo[b,d]pyran and carbazole analogues.

It seems that many sigma ligands have been designed from known sigma ligands. We focused on a difference in structural flexibility between haloperidol and apomorphine, and studied chemical modification of apomorphine, a compound with high affinity for dopamine D2 receptors but not for sigma receptors, for discovery of sigma ligands. The first modification yielded good results with 6H-dibenzo[b,d]pyran analogues with weak affinity for sigma receptors but not D2 receptors. Furthermore, carbazole analogues, compounds designed from 6H-dibenzo[b,d]pyran analogues, potentially acted at sigma receptors with high selectivity. This paper describes the design, synthesis and sigma/D2 selectivity of 6H-dibenzo[b,d]pyran and carbazole analogues.

Animals↗

Fluorescence in situ hybridization using 16S rRNA-targeted oligonucleotides reveals localization of methanogens and selected uncultured bacteria in mesophilic and thermophilic sludge granules.

16S rRNA-targeted in situ hybridization combined with confocal laser scanning microscopy was used to elucidate the spatial distribution of microbes within two types of methanogenic granular sludge, mesophilic (35 degrees C) and thermophilic (55 degrees C), in upflow anaerobic sludge blanket reactors fed with sucrose-, acetate-, and propionate-based artificial wastewater. The spatial organization of the microbes was visualized in thin sections of the granules by using fluorescent oligonucleotide probes specific to several phylogenetic groups of microbes. In situ hybridization with archaeal- and bacterial-domain probes within granule sections clearly showed that both mesophilic and thermophilic granules had layered structures and that the outer layer harbored mainly bacterial cells while the inner layer consisted mainly of archaeal cells. Methanosaeta-, Methanobacterium-, Methanospirillum-, and Methanosarcina-like cells were detected with oligonucleotide probes specific for the different groups of methanogens, and they were found to be localized inside the granules, in both types of which dominant methanogens were members of the genus Methanosaeta. For specific detection of bacteria which were previously detected by whole-microbial-community 16S ribosomal DNA (rDNA)-cloning analysis (Y. Sekiguchi, Y. Kamagata, K. Syutsubo, A. Ohashi, H. Harada, and K. Nakamura, Microbiology 144:2655-2665, 1998) we designed probes specific for clonal 16S rDNAs related to unidentified green nonsulfur bacteria and clones related to Syntrophobacter species. The probe designed for the cluster closely related to Syntrophobacter species hybridized with coccoid cells in the inner layer of the mesophilic granule sections. The probe for the unidentified bacteria which were clustered with the green nonsulfur bacteria detected filamentous cells in the outermost layer of the thermophilic sludge granule sections. These results revealed the spatial organizations of methanogens and uncultivated bacteria and their in situ morphologies and metabolic functions in both mesophilic and thermophilic granular sludges.

Anaerobiosis↗

[Portal and pulmonary hypertension in a patient with MCTD].

A 42-year-old woman with mixed connective tissue disease (MCTD) died due to the rupture of esophageal varices. The autopsy revealed fresh thrombi in the main trunk of the portal vein. Microscopic examination disclosed wide-spread periportal fibrosis and stenosis of peripheral portal veins without remodeling of hepatic lobular architecture, which was compatible to idiopathic portal hypertension (IPH). Anti-phospholipid antibody was negative. Accordingly it is likely that portal vein thrombosis developed secondary to IPH. In the literature 6 (37.5%) of 16 collagen vascular disease patients with IPH died, and three of them were due to rupture of esophageal varices. Therefore IPH should be considered to be one of the most important complications affecting its grave prognosis in patients with collagen vascular disease. The patient also had had pulmonary hypertension (PH) when the diagnosis of portal hypertension was made. In the literature we found 5 collagen vascular disease patients with both PH and IPH like this case. The most outstanding common clinical feature among these 6 patients was Raynaud's phenomenon associated with positive anti-RNP antibody. Moreover 5 of 6 cases including this case simultaneously developed both PH and IPH. The clinical course of these patients suggests there may be a common pathogenetic factor for these two lesions. A possible candidate involved in the pathogenesis of PH and IPH may be endothelin, one of the vasoactive substances, since its receptor is said to be expressed abundantly in pulmonary and portal vasculatures. However, further investigation is necessary to elucidate the mechanism of PH and IPH in collagen vascular diseases.

Adult↗

Nitric oxide modulates sympathetic control of left ventricular contraction in vivo in the dog.

Recently, evidence has been presented that nitric oxide (NO) modulates myocardial contraction induced by beta-adrenergic stimulation in vitro and in vivo. In this study, we investigated whether inhibition of the L-arginine NO system augments the positive inotropic response of the left ventricle to direct stimulation of the sympathetic nerves in vivo in the dog. Electrical stimulation was applied to the left stellate ganglion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz) and supramaximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomized dogs. Next, in the same dogs, N(omega)-nitro L-arginine methylester (L-NAME) was infused into the left anterior descending (LAD) coronary artery, and LSG stimulation repeated using the same protocol. Finally, L-arginine was infused into the LAD artery, and LSG stimulation repeated. We used the maximum of the first derivative of left ventricular pressure (LV max d P/dt) as an index of the myocardial contractility. Plasma epinephrine and norepinephrine concentrations were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME treatment in five of twelve dogs. L-NAME treatment significantly augmented the inotropic response of the left ventricle (percent change in the LV max dP/dt) to LSG submaximal stimulation trains from 164 +/- 13 to.212 +/- 21 (P < 0.03), from 187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P < 0.05), respectively. This response was reversed by L-arginine treatment. However, the inotropic response to the supramaximal stimulation train did not change after L-NAME and L-arginine treatment. L-NAME significantly increased plasma norepinephrine concentration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without changing plasma epinephrine concentration in the coronary sinus. It is concluded that the inhibition of the L-arginine NO system augmented the positive inotropic effect on the left ventricle during sympathetic nerve stimulation in normal dogs in vivo.

Animals↗

[Nonoperative management of major blunt renal lacerations with urinary extravasation: report of two cases].

Two cases of major blunt renal trauma with urinary extravasation managed by conservative treatment are presented herein. The first case: A 13-year-old girl fell from a bicycle. A computed tomographic (CT) scan showed right renal laceration with retroperitoneal hematoma. Renal arteriography showed evidence of fresh arterial bleeding without visualization of the lower pole. She was treated conservatively with superselective arterial embolization of the lower pole. She developed no urinoma with normal renal function. Renal renin and blood pressures stayed within the normal range in follow up studies. The second case: A 12-year-old boy fell from a tree and hit his right flank. A CT scan showed fragmentation of right renal cortex with retroperitoneal hematoma. He was treated conservatively as his vital signs remained stable, no active arterial bleeding was found no renal arteriography and both renal pelvis and ureters were well visualized by intra venous pyelography. Retroperitoneal hematoma was absorbed without formation of urinoma. Renal function remained within normal limits in follow up studies.

Adolescent↗

[A qualitative analytical method for nonpermitted food colors by HPLC].

The Ministry of Health and Welfare has been proposed an analytical method for food colors by HPLC. Conditions in the method and modified conditions of the proposed method were applied for permitted and nonpermitted food colors, and relative retention times were obtained. The relative retention times would be a clue of the confirmation of these nonpermitted colors by other method.

Chromatography, High Pressure Liquid↗

[Simultaneous analysis and detection of pesticides in fresh fruits and vegetables by HPLC and GC].

A method was established for simultaneous determination of pesticide residue in fresh fruits and vegetables by HPLC and GC. CH3CN extraction/NaCl partiton method was used in order to recover hydrophilic pesticide such as acephate, methamidophos. Dimethoate and methamidophos from okra and DDVP from strawberry were detected by GC. On the other hand confirmation method by GC and GC/MS was studied for peaks detected by HPLC with UV and/or FL detector. OPP, TBZ, imazalil chlorpyrifos etc. in citrus fruits were detected by the proposed method.

Chromatography, Gas↗

[Evaluation of therapy for dilated cardiomyopathy with heart failure by iodine-123 metaiodobenzylguanidine imaging: comparison with heart rate variability power spectral analysis].

The relationship between the myocardial uptake of iodine-123 metaiodobenzylguanidine (123I-MIBG) and heart rate variability parameters has not been determined. This study determined the relationship between the change in myocardial uptake of 123I-MIBG and improvement in left ventricular function after treatment, to determine the usefulness of 123I-MIBG imaging to assess the effect of therapy on heart failure due to dilated cardiomyopathy (DCM). 123I-MIBG imaging and power spectral analysis of heart rate variability were performed before and after treatment in 17 patients with heart failure due to DCM. The following parameters were compared before and after treatment: New York Heart Association (NYHA) functional class, radiographic cardiothoracic ratio (CTR), blood pressure, echocardiographic data [left ventricular end-systolic (LVDs) and end-diastolic (LVDd) diameters, left ventricular ejection fraction (LVEF)], plasma concentrations of norepinephrine and epinephrine, heart rate variability power spectral analysis data [mean low frequency (MLF) and high frequency power (MHF)] and the myocardium to mediastinum activity ratio (MYO/M) obtained in early and late images, and washout rate calculated by anterior planar imaging of 123I-MIBG. The NYHA functional class, LVEF, LVDs, CTR, MLF and MHF improved after treatment. Early MYO/M and late MYO/M improved after treatment. The rate of increase in late MYO/M was positively correlated with the rate of improvement of LVEF after treatment. Furthermore, the late MYO/M was negatively correlated with MLF. Washout rate revealed no correlation with hemodynamic parameters. These findings suggest that late MYO/M is more useful than washout rate to assess the effect of treatment on heart failure due to DCM. Furthermore, the 123I-MIBG imaging and heart rate variability parameters are useful to assess the autonomic tone in DCM with heart failure.

3-Iodobenzylguanidine↗

Production of granulocyte/macrophage and macrophage colony-stimulating factors by human thyrocytes in culture.

Monocytes/macrophages can be activated by the colony-stimulating factors (CSFs), granulocyte/macrophage CSF and macrophage CSF, and play a pivotal role in immune and inflammatory responses. We examined whether human thyrocytes can produce these CSFs. Interleukin-1 (IL-1) strongly up-regulated the gene and protein expression of the two CSFs. Interferon-gamma stimulated M-CSF expression but inversely suppressed GM-CSF expression in either basal or IL-1-stimulated condition. Thyrocytes prepared from Graves' thyroid tissues produced relatively larger amounts of GM-CSF in response to IL-1 and M-CSF in both basal and IL-1-stimulated conditions when compared to those obtained from normal and adenomatous goiter thyroid tissues. Thyrotropin attenuated M-CSF, but not GM-CSF, production. The present finding indicates that human thyrocytes themselves produce both GM-CSF and M-CSF, and thus may participate in immune and inflammatory responses through these CSFs production.

Cells, Cultured↗

[Endometrioid adenocarcinoma of the prostate: a case report].

A 69-year-old man was referred to our department with gross hematuria. Magnetic resonance imaging revealed the tumor directly invading the rectum. Biopsy of the tumor by transurethral resection demonstrated endometrioid adenocarcinoma of the prostate. Serum prostate specific antigen (PSA) level was normal. Because the tumor did not respond to hormonal therapy for a month, radical prostatectomy combined with rectal amputation was performed. Immunohistochemically, carcinoembryonic antigen was detected but PSA and prostatic acid phosphatase were not.

Aged↗

An anatomic study of neuropeptide immunoreactivities in the lumbar dura mater after lumbar sympathectomy.

STUDY DESIGN: The distribution and density of nerve innervation in the lumbar dura mater after lumbar sympathectomy were assessed in wistar rats. OBJECTIVE: To provide basic information on the interaction between sympathetic and sensory nerves in patients with low back pain. SUMMARY OF BACKGROUND DATA: Many studies have indicated that the sinuvertebral nerve has an important role in innervating the tissues around the vertebrae. However, the origin, innervating pattern, and connections between the nerves are still controversial. It is well known that pain is often accompanied with sympathetic symptoms and exaggerated by sympathetic stimuli. Occasionally, anesthetic block at the L2 or L3 sympathetic ganglion relieves low back pain or symptoms associated with low back pain. The authors assessed the changes of the density and distribution of nerve innervation of the lumbar dura mater after lumbar sympathectomy. METHODS: Normal adult rats were sympathectomized at L2-L3. The threshold for thermal noxious pain by hot-plate analgesia test and changes in neuropeptides in the lumbar dura mater and dorsal root ganglia using light microscopic immunohistochemistry were assessed and compared with control rats. RESULTS: In the hot-plate analgesia test, sympathectomized rats increased their hot-plate latency time compared with that of sham-operated rats. Density of calcitonin gene-related peptide immunoreactive fibers in sympathectomy side of the lumbar dura mater decreased to 45.5% compared with the contralateral side. The number and size of calcitonin gene-related peptide immunoreactive cells in dorsal root ganglia showed no difference between sympathectomized and contralateral side. CONCLUSION: Sympathectomy increased the pain threshold and made the sympathectomized rats hypesthetic. A large numbers of sensory fibers innervated the lumbar dura mater via L2-L3 sympathetic nerve in rats. Sympathectomy reduced the number of these nerve fibers in the lumbar dura mater. Sympathetic nerves may play an important role for low back pain involving the lumbar dura mater.

Animals↗

Involvement of bacterial antigens in immunoglobulin A nephropathy.

To investigate the involvement of bacterial antigens in Immunoglobulin A (IgA) nephropathy, we measured IgA, IgG and IgM antibodies to gram-negative Escherichia coli (E.coli) and Haemophilus influenzae (H.influenzae) by ELISA in 24 patients (11 males and 13 females) with IgA nephropathy and 22 normal controls (11 males and 11 females). The titers of IgA and IgM antibodies for E.coli and H.influenzae were significantly higher in the IgA nephropathy group than in the controls. In addition, IgA and IgM antibody titers for E.coli and H.influenzae showed a significant positive correlation with serum IgA and IgM levels. These findings suggest that subclinical infection by these bacteria stimulates IgA production and that this may be a factor in the development and progression of IgA nephropathy.

Adolescent↗

The herbal medicine sho-saiko-to induces nitric oxide synthase in rat hepatocytes.

We have examined the effects of the herbal medicine sho-saiko-to (SST) on nitric oxide (NO) biosynthesis in rat hepatocytes by measuring the stable end-product nitrite and the mRNA of inducible NO synthase (iNOS). Interferon-gamma (IFN) by itself failed to induce NO synthesis (IFN: 1-1,000 u/ml). SST also did not elicit NO synthesis at concentrations up to 300 micrograms/ml when administered alone, but dose-dependently induced NO production in the presence of IFN. Whereas SST or IFN induced barely detectable levels of iNOS mRNA when administered alone, a combination of SST and IFN markedly induced iNOS mRNA in the cells. SST also modestly increased NO synthesis caused by interleukin-1 or bacterial lipopolysaccharide as a single agent, or in combination with IFN. On the other hand, SST had no effects on the NO synthesis produced by iNOS which were already induced. Thus, we found that SST stimulates cultured hepatocytes to produce NO by inducing iNOS gene expression under appropriate conditions. The capability of SST to induce NO biosynthesis might be related to the therapeutic efficacy of SST on the liver diseases.

Amino Acid Oxidoreductases↗

Effect of cilazapril on vascular restenosis after percutaneous transluminal coronary angioplasty.

BACKGROUND: In experimental studies using cilazapril, the strongest inhibition of neointima formation was obtained when treatment was initiated 6 days before injury. The MERCATOR trial showed no reduction in restenosis with cilazapril given after percutaneous transluminal coronary angioplasty (PTCA). The purpose of this study is to determine whether previous administration of cilazapril could prevent restenosis. METHODS: A total of 167 patients were randomly and prospectively assigned to the cilazapril group or the control group. In the cilazapril group, 78 patients received a 2 mg dose of cilazparil daily, starting 7 days before PTCA and continuing for 6 months. Only 128 patients (cilazapril 56, control 72) completed the study because 39 dropped out. Coronary angiograms were evaluated by the quantitative coronary angiogram (QCA) system. RESULTS: There were no differences between the two groups of patients with regard to baseline clinical and angiographic characteristics. QCA analysis (cilazapril 66 lesions, control 101 lesions): the loss at follow-up in minimal lumen diameter was 0.36 +/- 0.57 mm in the cilazapril group and 0.57 +/- 0.75 mm in the control group (P < 0.05). Restenosis rate: in the cilazapril group, 16 of 56 patients (28.6%) had restenosis in contrast to 36 of 72 patients (50.0%) in the control group (P < 0.02). When vessel restenosis was evaluated, 16 of 63 vessels (25.4%) demonstrated restenosis in the cilazapril group, in contrast to 41 of 82 vessels (50.0%) in the control group (P < 0.01). CONCLUSIONS: Treatment using cilazapril 7 days before PTCA significantly reduced the rate of restenosis. These data suggest that previous administration of cilazapril might be important for preventing restenosis.

Aged↗

Quantitative double-tracer autoradiography with tritium and carbon-14 using imaging plates: application to myocardial metabolic studies in rats.

UNLABELLED: A system for 3H- and 14C-labeled macroautoradiography was developed that is able to quantify the tissue radioactivity of two tracers using imaging plates. METHODS: Discrimination between electrons emitted from 3H and 14C is possible on the basis of their different energy distributions. The general use imaging plate with a protective layer detects 14C radioactivity, but it does not detect 3H radioactivity which has a lower energy distribution than 14C. Recently, a 3H-sensitive imaging plate without a protective layer was developed. The 3H distribution image is obtained by subtracting the UR image from the TR image. For quantification of the tissue radioactivity of 3H and 14C, we obtained tissue equivalent values (Bq/mg) of commercially available 3H- and 14C-labeled graded standards using different dilutions of labeled heart paste and liquid scintillation counting. Using the 3H- and 14C-labeled graded standards, we confirmed the validity of the quantification of the 3H-autoradiographic intensity using this subtraction method. We applied this method to a rat model of acute myocardial ischemia to compare regional myocardial free fatty acid uptake determined by beta-methyl[1-14C]heptadecanoic acid to glucose uptake determined by 2-deoxy-D-[1-3H]glucose. RESULTS: Free fatty acid uptake was decreased sharply at the ischemic periphery where glucose uptake was preserved. CONCLUSION: This double-tracer autoradiography with 3H and 14C which has high sensitivity, a high spatial resolution of 50 microns and superior linearity with a wide dynamic range of 10(4) to 10(5) allows accurate quantification of the tissue radioactivity of the two radiopharmaceuticals.

Animals↗

Glycogenolytic activity of pituitary adenylate cyclase activating polypeptide (PACAP) in vivo and in vitro.

When pituitary adenylate cyclase activating polypeptide (PACAP-38, 420 pmol/kg) was injected to anesthetized dogs, hyperglycemia associated with elevation in plasma glucagon and adrenalin levels was observed. In dogs undergone adrenalectomy, the same dose of it stimulated insulin, but not glucagon, release and hyperglycemia was not observed. Much higher dose was needed to evoke hyperglycemia in such dogs. Next, direct glycogenolytic activities of PACAP, glucagon and adrenalin were studied on cultured rat hepatocytes. PACAP38 stimulated glucose output via cAMP production by the cells, but the potency was far less than that of glucagon. Adrenalin, however, could not exert the activity with physiological concentrations. These results indicate that hyperglycemic effect of PACAP can be attributed mainly to indirect effects resulting from glucagon and adrenalin release and possibly in part to a direct action on hepatocytes.

Adrenalectomy↗

Intrapleural omentum simulating pleural effusion.

We report herein a case of Morgagni hernia of omentum into the pleural space, simulating a pleural effusion on a routine chest radiograph. A 62-year-old man was referred to our clinic for close examination of a pleural effusion-like shadow at the right costophrenic region. He had no history of trauma and no symptoms. Chest computed tomographic scan showed a pleural effusion-like shadow with a fat density. Thoracoscopy revealed a movable omentum-like mass and no significant fluid in the right pleural space. Magnetic resonance imaging and celiac angiography confirmed the herniation of omentum into the right pleural space. This case suggests that a Morgagni hernia must be excluded in a patient with a fat density effusion-like shadow in the pleural space.

Diagnosis, Differential↗

Effect of NG-nitro-L-arginine on shock induced by endotoxin and by platelet activating factor in dogs.

When NG-nitro-L-arginine, a nitric oxide synthase inhibitor, administration was started 5 min prior to shock induction in anesthetized dogs, a partial restoration was observed in endotoxin-induced shock and a complete recovery in platelet activating factor (PAF)-induced shock. When NG-nitro-L-arginine infusion was started 5 min after shock induction, no significant recovery was observed in endotoxin-induced shock and a complete recovery in PAF-induced shock. These data indicate that enhanced production of nitric oxide by vascular endothelial cells may contribute to endotoxin- or PAF-induced shock and also that some mediators including inducible nitric oxide synthase and/or cellular damage might be involved in endotoxin-induced shock.

Amino Acid Oxidoreductases↗