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Biomedical subjects

T Morimoto

Publications and source records attributed to T Morimoto.

At least 37 records · Page 2Linked to original sources

Brain histamine and feeding behavior.

Food intake is regulated by many endogenous substances, such as peptides and neurotransmitters in the central nervous system. Based on the clinical observation that some antidepressants and antipsychotics with antihistaminic activity stimulate food intake and increase body weight, histamine has been thought to be an anorectic agent. Several lines of evidence suggest that histamine decreases food intake via H(1)-receptors (H1R) at least in the ventromedial hypothalamus or the paraventricular nucleus. Recently, mutant mice lacking H1R were generated and the interaction between the histaminergic system and leptin-induced suppression of food intake was evidenced by using these mice. In regulating food intake, histamine is indicated to functionally associate with neuropeptide Y, peptide YY, and bombesin. However, the question remained as to why the circadian variation in the level of histamine is inversely correlated to the pattern of feeding.

Animals↗

Microfluidic device for airborne BTEX detection.

We fabricated a microfluidic device for the optical detection of airborne benzene, toluene, ethylbenzene and xylenes (BTEX). The device consists of concentration and detection cells formed of 3 cm x 1 cm Pyrex plates. The concentration cell is composed of an adsorbent to concentrate the BTEX gases and a thin-film heater todesorb the concentrated gases from the adsorbent thermally. The collected gases are introduced into the detection cell, which is connected to optical fibers, to measure their absorption spectra. We optimized the device's operating conditions by studying the thermal characteristics of the concentration cell and the time profile of the gas concentration flowing in the detection cell. We used the device under optimized operating conditions to detect toluene gas as a typical example BTEX. The gas concentration amplification rate was approximately 2 orders of magnitude, and we successfully measured parts-per-million levels of toluene gas with this device.

Air Pollutants↗

Calcineurin-GATA4 pathway is involved in beta-adrenergic agonist-responsive endothelin-1 transcription in cardiac myocytes.

Increases in the expression of endothelin-1 (ET-1) in cardiac myocytes play a critical role in the development of heart failure in vivo. Whereas norepinephrine (NE) is a potent inducer of ET-1 expression in cardiac myocytes, the signaling pathways that link NE to inducible cardiac ET-1 expression are unknown. Adrenergic stimulation results in an increase in intracellular calcium levels, which in turn activates calcineurin. Here, we have shown that stimulation with NE markedly increased the expression of the ET-1 gene in primary cardiac myocytes from neonatal rats. This increase was severely attenuated by a beta-adrenergic antagonist, metoprolol, but not by an alpha-adrenergic antagonist, prazosin. Consistent with these data, the beta-adrenergic agonist isoproterenol (ISO) activated the rat ET-1 promoter activity to an extent that was similar to NE. The ISO-stimulated increase in promoter activity was significantly inhibited by a Ca(2+)-antagonist, nifedipine, and an immunosuppressant, cyclosporin A, which blocks calcineurin. Mutation analysis indicated that the GATA4 binding site is required for ISO-responsive ET-1 transcription. Stimulation with ISO enhanced the interaction between NFATc and GATA4 in cardiac myocytes. Consistent with this interaction, overexpression of GATA4 and NFATc synergistically activated the ET-1 promoter. These findings demonstrate that NE-stimulated ET-1 expression in cardiac myocytes is mediated predominantly via a beta-adrenergic pathway, and that calcium-activated calcineurin-GATA4 plays a role in this process.

Adrenergic beta-Agonists↗

Calcineurin pathway is required for endothelin-1-mediated protection against oxidant stress-induced apoptosis in cardiac myocytes.

Endothelin-1 (ET-1) acts not only as a growth-promoting peptide but also as a potent survival factor against myocardial cell apoptosis. However, the signaling pathways leading to myocardial cell protection by ET-1 are poorly understood. Using a culture system of primary cardiac myocytes derived from neonatal rats, we show in the present study that ET-1 almost completely blocked the hydrogen peroxide-induced increase in the percentage of TdT-mediated dUTP-biotin nick-end labeling-positive myocytes. Apoptosis inhibition by ET-1 was confirmed by cytofluorometric analysis as well as by examination of the ladder formation, morphological features, and caspase-3 cleavage. We have found that ET-1 converts the nuclear factor of activated T lymphocytes (NFATc) in cardiac myocytes into high-mobility forms and translocates cytoplasmic NFATc to the nuclei. In addition, ET-1 stimulates the interaction between NFATc and the cardiac-restricted zinc-finger protein GATA4 in these cells. The immunosuppressants cyclosporin A and FK506, which antagonize calcineurin, negated the inhibitory effect of ET-1 on apoptosis. Calcineurin activation de novo was sufficient to inhibit hydrogen peroxide-induced apoptosis. ET-1 induced the expression of an antiapoptotic protein bcl-2 in cardiac myocytes in a cyclosporin A-dependent manner, but it did not alter the expression of bax. Cyclosporin A also attenuated the ET-1-stimulated transcription of the bcl-2 gene in these cells. These findings demonstrate that the calcineurin pathway is required for the inhibitory effect of ET-1 on oxidant stress-induced apoptosis in cardiac myocytes.

Active Transport, Cell Nucleus↗

Analysis of the metabolites of the sodium salt of 6-hydroxy-5-(phenylazo)-2-naphthalenesulfonic acid in Sprague-Dawley rat urine.

The sodium salt of 6-hydroxy-5-(phenylazo)-2-naphthalenesulfonic acid (SS-AN), which is a subsidiary color present in Food Yellow No. 5 [Sunset Yellow FCF, disodium salt of 6-hydroxy-5-(4-sulfophenylazo)-2-naphthalenesulfonic acid], was orally administered to Sprague-Dawley rats. Metabolite A, metabolite B, and unaltered SS-AN were detected as colored metabolites in the rat urine. Analysis of the chemical structures showed that metabolite A (major peak) was 6-hydroxy-5-(4-sulfooxyphenylazo)-2-naphthalenesulfonic acid, the sulfuric acid conjugate of SS-AN, and metabolite B (minor peak) was 6-hydroxy-5-(4-hydroxyphenylazo)-2-naphthalenesulfonic acid (SS-PAP), which is a derivative of metabolite A without the sulfuric acid. The colorless metabolites p-aminophenol, o-aminophenol, and aniline present in the urine were analyzed by liquid chromatography-mass spectrometry. The orally administered SS-AN had been metabolized to the colorless metabolites (p-aminophenol 45.3%, o-aminophenol 9.4%, aniline 0.4%) in the 24-h urine samples. Analysis of the colored metabolites by high-performance liquid chromatography with detection at 482 nm indicated the presence of metabolite A (0.29%), SS-PAP (0.01%), and SS-AN (0.02%) were detected in the 24-h urine samples. Approximately 56% of SS-AN was excreted into the urine and the rest is probably excreted into feces.

Animals↗

Selectivity of stationary phases in reversed-phase liquid chromatography based on the dispersion interactions.

Selectivity of 15 stationary phases was examined, either commercially available or synthesized in-house. The highest selectivity factors were observed for solute molecules having different polarizability on the 3-(pentabromobenzyloxy)propyl phase (PBB), followed by the 2-(1-pyrenyl)ethyl phase (PYE). Selectivity of fluoroalkane 4,4-di(trifluoromethyl)-5,5,6,6,7,7,7-heptafluoroheptyl (F13C9) phase is lowest among all phases for all compounds except for fluorinated ones. Aliphatic octyl (C8) and octadecyl (C18) phases demonstrated considerable selectivity, especially for alkyl compounds. While PBB showed much greater preference for compounds with high polarizability containing heavy atoms than C18 phase, F13C9 phase showed the exactly opposite tendency. These three stationary phases can offer widely different selectivity that can be utilized when one stationary phase fails to provide separation for certain mixtures. The retention and selectivity of solutes in reversed-phase liquid chromatography is related to the mobile phase and the stationary phase effects. The mobile phase effect, related to the hydrophobic cavity formation around non-polar solutes, is assumed to have a dominant effect on retention upon aliphatic stationary phases such as C8, C18. In a common mobile phase significant stationary phase effect can be attributed to dispersion interaction. Highly dispersive stationary phases such as PBB and PYE retain solutes to a significant extent by (attractive) dispersion interaction with the stationary phase ligands, especially for highly dispersive solutes containing aromatic functionality and/or heavy atoms. The contribution of dispersion interaction is shown to be much less on C18 or C8 phases and was even disadvantageous on F13C9 phase. Structural properties of stationary phases are analyzed and confirmed by means of quantitative structure-chromatographic retention (QSRR) study.

Chromatography, Liquid↗

Unique biochemical nature of carp retinol-binding protein. N-linked glycosylation and uncleavable NH2-terminal signal peptide.

Retinol transport and metabolism have been well characterized in mammals; however, very little is known in fish. To study the mechanism by which fish retinol-binding protein (RBP) is able to remain in plasma besides its small molecular size, we isolated RBP cDNA from a carp liver cDNA library. Comparison of the deduced amino acid sequence with that of known vertebrate RBPs showed that carp RBP has high homology to the other cloned vertebrate RBPs, but it lacks the COOH-terminal tetrapeptide, RNL(S)L, which is most likely involved in the interaction with transthyretin in mammalian RBPs. In addition, the primary structure of carp RBP contains two consensus N-linked glycosylation sites that represent a unique feature. We have obtained experimental evidence, by in vitro and in vivo expression experiments, that both sites are indeed glycosylated. We have also characterized the protein as a complex type N-linked glycoprotein by lectin binding assay, neuraminidase and endoglycosidase H and F digestion. Inhibition of glycosylation by tunicamycin treatment of transfected cells caused a great reduction of RBP secretion. Since kidney filtration of anionic proteins is less than half that of neutral protein of the same size, this finding strongly suggests that the amount of carp RBP filtration through kidney glomeruli may be reduced by a glycosylation-dependent increase in the molecular size and negative charge of the protein. A second unique feature of carp RBP as secretory protein is the presence of a nonconserved NH(2)-terminal hydrophobic domain, which functions as an insertion signal but is not cleaved cotranslationally and remains in the secreted RBP.

Amino Acid Sequence↗

Depressive symptoms among poststroke patients in Japan: frequency distribution and factor structure of the GDS.

OBJECTIVE: The present study examined the nature, prevalence, and covariates of depressive symptoms among home-dwelling poststroke patients in Japan using the Geriatric Depression Scale Short Form (GDS-1). Poststroke results were compared with those of elderly with affective disorders and with those of healthy nonstroke elderly. METHODS: Poststroke patients (n = 101) who did not also have a diagnosis of Alzheimer's dementia, were identified from patient records at seven randomly selected hospitals with outpatient rehabilitation clinics in a metropolitan area in western Japan and invited to participate in the study. All instruments were interview-administered. RESULTS: GDS scores did not correlate with age, sex, education, functional dependence, aphasia, paralysis or presence of other chronic illnesses. However, GDS scores did correlate significantly with self-rated general health and poststroke duration. Compared with the frequency distribution in a psychiatric sample, poststroke patients had higher positive affect and lower depressed mood but similar social withdrawal scores. The factor structure of the poststroke sample differed from that of nonstroke elderly in that depressed mood items loaded with items for energy loss and memory problems. CONCLUSION: Despite the fact that 62% of subjects scored > or = 6 on the GDS, none were currently receiving assessment and/or treatment for their depressive symptoms. The frequency distribution and factor structure suggest that poststroke GDS scores reflect endorsement of functional losses such as decreased energy and impaired memory and subsequent feelings of helplessness, boredom and social withdrawal rather than decreased positive affect. Treatment should focus on dealing with these issues.

Aged↗

Use of a segment of transverse colon as a gastric substitute after total gastrectomy: an audit of 18 patients.

BACKGROUND: Various types of reconstruction have been employed in attempts to improve the quality of life after total gastrectomy. The use of a jejunal pouch has been the most common approach, and preservation of the duodenal passage has been recommended in several related studies. The aim of the present study was to investigate the benefit of the use of a segment of transverse colon as a gastric substitute. METHODS: Isoperistaltic interposition with a segment of transverse colon was performed after total gastrectomy in 18 patients with gastric malignancies. To clarify the benefits and disadvantages of this technique, a comparison was made between these patients and another 17 patients who underwent jejunal interposition without a pouch. The parameters to be compared included operation time, amount of blood loss, incidence of postoperative complications, and changes in body weight. RESULTS: Postoperative complications were more frequent in the patients reconstructed with the transverse colon, despite a lower incidence of extended lymphadenectomies in this group of patients. No advantage over those treated by the jejunal interposition, in terms of postoperative body weight, was evident during 2 years of follow-up. CONCLUSION: Although it may be too early to draw definite conclusions, there seems to be little benefit in the use of the transverse colon as a gastric substitute.

Carcinoma↗

A new approach to mRNA in proximal tubule cells of patients with CLCN5 channelopathy.

ClC-5 is a chloride channel whose gene mutations have been reported to be associated with X-linked nephrolithiasis (XRN), X-linked recessive hypophosphatemic rickets (XLRH), Dent disease, and idiopathic low-molecular-weight proteinuria (ILMWP) in Japanese children. To establish more efficient screening for CLCN5 abnormalities, we developed a new diagnostic method using reverse transcription and polymerase chain reaction (RT-PCR) of cultured renal tubular cells from the urine of patients. Using this new method, we successfully detected microdeletion of ClC-5 mRNA in a patient and splicing abnormality of the CLCN5 Cl channel.

Cells, Cultured↗

Lymph node metastasis in cancer of the middle-third stomach: criteria for treatment with a pylorus-preserving gastrectomy.

A retrospective study was conducted to establish the criteria for performing a pylorus-preserving gastrectomy. This study was performed on 491 patients who had cancer of the middle-third stomach and had been curatively treated with a distal gastrectomy. The incidence of node metastasis for each lymph node station (the group of regional lymph nodes which have been anatomically defined and classified by the Japanese Classification of Gastric Carcinoma) was evaluated with reference to the depth of invasion, tumor size, and circumferential location, to show any significant correlations with an increase in tumor diameter or in the depth of tumor invasion. The benefits of resecting each station was then evaluated based on the incidence of metastasis to each station and the rate of long-term survivors among those with metastasis to each station. The benefit was substantial for the lymph nodes along the lesser curvature, along the right gastroepiploic artery, and at the base of the left gastric artery, while the advantages were almost negligible for the suprapyloric nodes and right paracardial nodes. In conclusion, carcinoma that fulfills either of the following conditions may thus be indicated to undergo a pylorus-preserving gastrectomy: (i) restricted to a depth of m or sml, (ii) a depth of sm2 or mp with a diameter of less than 2cm, (ii) a depth of sm2 or mp and located in the greater curvature.

Adult↗

Cerebral aneurysms in the perforating artery manifesting intracerebral and subarachnoid haemorrhage--report of two cases.

BACKGROUND: An arteriosclerotic aneurysm in the perforating artery has been focused on as a causative factor for hypertensive intracerebral haemorrhage. However, its pathogenesis remains unknown, and its existence is still a controversy. CASE DESCRIPTION: A 62-year-old female and a 70-year-old male with a history of hypertension suffered from intracerebral haemorrhage accompanied by subarachnoid haemorrhage. Cerebral angiograms demonstrated an aneurysm arising from the perforating artery at the central location of the haematoma in both cases. The aneurysms were confirmed as the cause of bleeding during microsurgery, and were resected. Histological examination of the surgical specimens revealed that the walls of the aneurysms lacked internal elastic lamina and consisted only of the adventitia. CONCLUSION: These findings demonstrate that the aneurysm in the perforating artery can be a causative factor for hypertensive intracerebral haemorrhage, and indicate that the loss of internal elastic lamina induced by hypertension may contribute to the formation of the aneurysm of the perforating artery.

Aged↗

Trigeminal neuralgia associated with achondroplasia. Case report with literature review.

A 59-year-old male with a history of 2 years of typical trigeminal neuralgia manifested the characteristics of achondroplasia. X-ray and magnetic resonance imaging demonstrated basilar impression, deformity of the posterior fossa with marked asymmetry of petrous bone and compression of pons and trigeminal nerve by the left vertebral artery and anterior inferior cerebellar artery. Microvascular decompression was performed through a suboccipital craniectomy. The neuralgia disappeared soon after surgery and remains completely resolved until today. This is the first reported case of trigeminal neuralgia in a patient with achondroplasia. The deformity of the skull base was considered to influence the development of the trigeminal neuralgia.

Achondroplasia↗

Perimetric sensitivity and retinal thickness in eyes with macular edema resulting from branch retinal vein occlusion.

PURPOSE: To document and study the relationship between perimetric sensitivity and retinal thickness at the foveal and parafoveal points in eyes with macular edema associated with branch retinal vein occlusion. METHODS: A prospective study was performed using the central 10-2 Humphrey perimetry program and optical coherence tomography. Seventeen eyes with branch retinal vein occlusion were eligible showing macular edema without macular nonperfusion or massive retinal hemorrhage. RESULTS: The sensitivity and retinal thickness were significantly correlated at the fovea (r = -0.629, P =.006) as well as 1 (r = -0.656, P <.0001) and 3 (r = -0.885, P <.0001) degrees apart from the fovea. The visual acuity that is expressed as a logarithm of the minimum angle of resolution (LogMAR) also correlated with retinal thickness (r = 0.591, P =.011). CONCLUSION: The increased retinal thickness resulting from macular edema is closely correlated with retinal sensitivity as measured by automated static perimetry both at the fovea and parafovea. Measuring the retinal thickness using optical coherence tomography may be useful in monitoring macular edema in eyes with branch retinal vein occlusion.

Adult↗

Effect of Ca(2+)-free and Mg(2+)-free BSS Plus solution on the retinal pigment epithelium and retina in rabbits.

PURPOSE: To determine whether intravitreal irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus (Alcon Laboratory, Fort Worth, Texas) solution alters the adhesiveness between the retinal pigment epithelium and the retina of rabbits. METHODS: Thirty-four eyes of 34 Dutch pigmented rabbits underwent lensectomy and vitrectomy. Subsequently, the vitreous cavity of 24 eyes was irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 10 or 20 minutes. The other 10 eyes were irrigated with BSS Plus solution for 20 minutes as controls. To determine the adhesiveness between the retinal pigment epithelium and retina, a retinal detachment was produced in 12 of the 34 eyes. The apical surface of the retinal pigment epithelium and the photoreceptor outer segments were examined by scanning electron microscopy. Retinal physiology was assessed by electroretinography and retinal morphology by light microscopy. RESULTS: After retinal detachment was produced, the number of cone sheaths on the apical surface of the retinal pigment epithelium after irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes (33 +/- 15, mean +/- SD) was significantly less than the number of cone sheaths on the apical surface of the retinal pigment epithelium of eyes after irrigation with BSS Plus solution for 20 minutes (120 +/- 50) or the number of cone sheaths on the apical surface of the retinal pigment epithelium of eyes after 10 minutes of irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution (115 +/- 49; P =.02). The b-wave amplitudes in the eyes irrigated with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes were depressed compared with the b-waves in eyes irrigated with BSS Plus solution for 20 minutes on the first postoperative day (P =.03). After the third postoperative day, there was no significant difference in the b-waves (P >.06). Light microscopy demonstrated no morphologic abnormalities after the use of both solutions. CONCLUSIONS: Intravitreal irrigation with Ca(2+)-free and Mg(2+)-free BSS Plus solution for 20 minutes altered the adhesion between the retinal pigment epithelium microvilli and retinal outer segments and made the creation of retinal detachment less traumatic. These results suggest that Ca(2+)-free and Mg(2+)-free BSS Plus solution may be of clinical value for the creation of an intentional retinal detachment for foveal translocation surgery.

Animals↗