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Biomedical subjects

R Takeda

Publications and source records attributed to R Takeda.

At least 37 records · Page 2Linked to original sources

Synaptic interactions between respiratory neurons during inspiratory on-switching evoked by vagal stimulation in decerebrate cats.

To elucidate neuronal mechanisms underlying phase-switching from expiration to inspiration, or inspiratory on-switching (IonS), postsynaptic potentials (PSPs) of bulbar respiratory neurons together with phrenic nerve discharges were recorded during IonS evoked by vagal stimulation in decerebrate and vagotomized cats. A single shock stimulation of the vagus nerve applied at late-expiration developed an inspiratory discharge in the phrenic neurogram after a latency of 79+/-11 ms (n = 11). Preceding this evoked inspiratory discharge, a triphasic response was induced, consisting of an early silence (phase 1 silence), a transient burst discharge (phase 2 discharge) and a late pause (phase 3 pause). During phase 1 silence, IPSPs occurred in augmenting inspiratory (aug-I) and expiratory (E2) neurons, and EPSPs in postinspiratory (PI) neurons. During phase 2 discharge, EPSPs arose in aug-I neurons and IPSPs in PI and E2 neurons. These initial biphasic PSPs were comparable with those during inspiratory off-switching evoked by the same stimulation applied at late-inspiration. In both on- and off-switching, phase-transition in respiratory neuronal activities started to arise concomitantly with the phrenic phase 3 pause. These results suggest that vagal inputs initially produce a non-specific, biphasic response in bulbar respiratory neurons, which consecutively activates a more specific process connected to IonS.

Animals↗

Synaptic potentials in respiratory neurones during evoked phase switching after NMDA receptor blockade in the cat.

1. Blockade of NMDA receptors by dizocilpine impairs the inspiratory off-switch (IOS) of central origin but not the IOS evoked by stimulation of sensory afferents. To investigate whether this difference was due to the effects of different patterns of synaptic interactions on respiratory neurones, we stimulated electrically the superior laryngeal nerve (SLN) or vagus nerve in decerebrate cats before and after i.v. administration of dizocilpine, whilst recording intracellularly. 2. Phrenic nerve responses to ipsilateral SLN or vagal stimulation were: at mid-inspiration, a transient inhibition often followed by a brief burst of activity; at late inspiration, an IOS; and at mid-expiration, a late burst of activity. 3. In all neurones (n = 16), SLN stimulation at mid-inspiration evoked an early EPSP during phase 1 (latency to the arrest of phrenic nerve activity), followed by an IPSP in inspiratory (I) neurones (n = 8) and by a wave of EPSPs in post-inspiratory (PI) neurones (n = 8) during phase 2 (inhibition of phrenic activity). An EPSP in I neurones and an IPSP in PI neurones occurred during phase 3 (brief phrenic burst) following phase 2. 4. Evoked IOS was associated with a fast (phase 1) activation of PI neurones, whereas during spontaneous IOS, a progressive (30-50 ms) depolarization of PI neurones preceded the arrest of phrenic activity. 5. Phase 3 PSPs were similar to those occurring during the burst of activity seen at the start of spontaneous inspiration. 6. Dizocilpine did not suppress the evoked phrenic inhibition and the late burst of activity. The shapes and timing of the evoked PSPs and the changes in membrane potential in I and PI neurones during the phase transition were not altered. 7. We hypothesize that afferent sensory pathways not requiring NMDA receptors (1) terminate inspiration through a premature activation of PI neurones, and (2) evoke a late burst of phrenic activity which might be the first stage of the inspiratory on-switch.

Animals↗

99mTc-tetrofosmin uptake in bone metastases from breast cancer.

99mTc-tetrofosmin myocardial imaging was performed in a 62-year-old woman who had undergone standard radical mastectomy for right breast cancer 6 years ago. Although the result was negative for the ischemic heart disease, it showed abnormal accumulation corresponding to the bone metastases in the spine. We believe that 99mTc-tetrofosmin imaging is helpful in detecting bone metastases from breast cancer.

Bone Neoplasms↗

NMDA receptor-mediated inspiratory off-switching in pneumotaxic-disconnected cats.

The pneumotaxic center is thought to govern inspiratory off-switching (IOS), and blockade of N-methyl-D-aspartate (NMDA) receptors by dizocilpine impairs IOS causing apneusis. The present study is to examine whether the NMDA receptor-mediated IOS mechanism functions in the medullary respiratory network after disconnecting the pneumotaxic center. In decerebrate and vagotomized cats, the nucleus parabrachialis medialis (NPBM) and vagus nerves were stimulated to evoke IOS and a dorsal pontine transection was performed while the central respiratory activity was recorded in phrenic neurogram. The transection eliminated the NPBM-stimulated IOS but not the vagally evoked IOS, and developed two types of respiration; eupnea in 12 and apneusis in six out of 18 cats. Apneustic respiration was not changed into eupneic one by changing the end-tidal CO2 level. In animals displaying eupnea after the transection, dizocilpine (0.3 mg/kg i.v.) produced apneusis, characterized by a prolonged inspiration, a shortened stage 1 expiration and an unchanged stage 2 expiration. Dizocilpine caused no further change in the apneustic pattern induced by the transection. The present results suggest that the medullary respiratory network is able to generate a eupneic respiration after disconnecting the pontine pneumotaxic center, and the NMDA mechanism plays an important role in the medullary respiratory network.

Age Factors↗

Aldosterone overproduction and CYP11B2 mRNA overexpression in vessels of spontaneously hypertensive rats.

Aldosterone is synthesized in extra-adrenal tissues such as blood vessels and brain. Damage to blood vessels could play a crucial role in perpetuating hypertension. In this study, we determined both aldosterone production and aldosterone synthase gene-CYP11B2 mRNA expression in vessels of spontaneously hypertensive rats (SHR). The results showed that aldosterone was overproduced in the vasculature of SHR, by means of ex vivo mesenteric artery perfusion, HPLC, and RIA, and that CYP11B2 mRNA expression was upregulated in aortas of SHR, confirmed by RT-PCR and Southern blot.

Aldosterone↗

Lisinopril decreases plasma free testosterone in male hypertensive patients and increases sex hormone binding globulin in female hypertensive patients.

The effect of an angiotensin-converting enzyme inhibitor, lisinopril, on gonadal hormones was assessed in 20 patients with essential hypertension. A daily dose of 5 to 20 mg of lisinopril was administered for 6 mo. In male patients, the free testosterone (f-T) concentration decreased significantly (before, 13.8+/-2.4 pg/ml; after, 9.9+/-1.5 pg/ml: mean +/- SEM, p < 0.05), whereas the plasma total testosterone (T), estradiol (E2), and sex hormone binding globulin (SHBG) concentrations were not significantly affected. Lisinopril had no effect on plasma T, f-T, or E2 concentrations in female patients, but significantly increased the plasma SHBG concentration (before, 48.0 6.1 nmol/l; after, 62.7+/-6.7 nmol/l: p < 0.01). The results of this preliminary study suggest that lisinopril affects plasma f-T and SHBG concentrations. The clinical implications of lisinopril-induced changes in plasma f-T and SHBG concentrations remain to be clarified.

Aged↗

Micacocidin A, B and C, novel antimycoplasma agents from Pseudomonas sp. II. Structure elucidation.

Metal-containing novel heterocyclic antibiotics, micacocidin A (1), B (2), and C (3) have been isolated from the culture filtrate of Pseudomonas sp. No. 57-250. The structure and absolute configuration of micacocidin A, an octahedral Zn2+ complex, was determined by X-ray crystallographic analysis. And then, the structures of the two congeners, micacocidin B (Cu2+ complex) and C (Fe3+ complex) were investigated by employing one dimensional and two dimensional homonuclear and heteronuclear NMR spectroscopies and mass spectrometry.

Anti-Bacterial Agents↗

Immunohistochemical and structural characteristics of the reticular framework of the white pulp and marginal zone in the human spleen.

BACKGROUND: The reticular framework of the white pulp (WP) and marginal zone (MZ) consists of reticulum cells and reticulin fibers. The antigenic heterogeneity of the reticular framework is well documented in the mouse and rat spleen. The aim of the present study is to characterize the reticular framework of the WP and MZ of the human spleen. METHODS: Nine surgically resected human spleens were investigated. Five of the nine spleens were perfused. Formalin-fixed materials were embedded in paraffin and serial sections prepared for hematoxylin-eosin, silver staining, and immunohistochemical examination. Electron and immuno-electron microscopy were also applied. Using confocal laser scanning microscopy, the reticular framework was analyzed three-dimensionally. RESULTS: The reticulin fibers of the framework were immunostained for type IV collagen in the WP and MZ. The WP was three-dimensionally delimited by the alpha-smooth muscle actin (alpha-SMA)-positive reticulum cells. In the WP, the distribution of alpha-SMA-positive reticulum cells formed the reticular framework of the periarteriolar lymphoid sheath (PALS). They also ensheathed the reticulin fibers. Interdigitating cells (IDCs) were scattered throughout the framework. A few IDCs attached to the framework. In the lymph follicle (LF), reticulum cells were not alpha-SMA-positive. The mesh of follicular dendritic cells (FDCs) was found in the germinal center. In places, the reticulin fibers were involved in the mesh of the FDCs and covered by the cytoplasm of FDCs. In the MZ, alpha-SMA-positive reticulum cells were arranged in a mesh pattern and ensheathed the fine reticulin fibers. CONCLUSION: The reticular framework of the PALS, LF, and MZ is specialized into heterogeneous components in the human spleen. The heterogeneity of the framework may induce the segregation of T and B lymphocytes.

Actins↗

Quantification of regional cerebral blood flow and vascular reserve in childhood moyamoya disease using [123I]IMP-ARG method.

Both regional cerebral blood flow (rCBF) and regional vascular reserve (rVR) in ten childhood Moyamoya disease were quantified pre- and post-operatively by autoradiographic processing using single photon emission computed tomography (SPECT) and N-isopropyl-rho-iodoamphetamine (IMP) (IMP-ARG method) to estimate hemodynamic effectiveness of surgical revascularization. Before surgery, in two patients, rCBF was reduced in the whole territories and loss of rVR in the anterior circulation was observed; +4.3% in the anterior cerebral artery (ACA), -3.0% in the middle cerebral artery (MCA) and +17.5% in posterior cerebral artery (PCA) territories. After surgery, in eight patients without transient ischemic attack (TIA) episodes, rCBF at rest was maintained around subnormal level in the whole territories, and mean rVR was up to +11.9, +17.3 and +28.3% in ACA, MCA and PCA territories, respectively. However, rVR in the anterior circulation was significantly reduced in comparison with rVR in the posterior circulation. Quantification of both resting rCBF and rVR using IMP-ARG method could provide reliable information concerning on surgical indication and its effectiveness in childhood Moyamoya disease.

Adolescent↗

Effects of isoflurane on brain stem blood flow and renal sympathetic nerve activity during induced hypotension.

Effects of isoflurane on arterial blood pressure, regional blood flow in the brain stem, and renal sympathetic nerve activity were compared with those during vasodilator-induced hypotension using decerebrate unanesthetized cats. Either prostaglandin E1 (PGE1) or trinitroglycerin (TNG) was used to decrease the mean arterial pressure 30% below the control level. The effects of isoflurane (0.5 MAC for 15 min) were examined in the following three conditions: (1) during PGE1-induced hypotension; (2) during TNG-induced hypotension, and (3) without either vasodilator. Isoflurane decreased the brain stem blood flow in parallel with a systemic blood pressure fall. Electrical activity of the renal sympathetic nerve consisted of a high-amplitude phasic and a low-amplitude tonic discharge. Isoflurane decreased the phasic activity and increased the tonic activity. Although the two vasodilators had a similar effect on systemic blood pressure and renal sympathetic discharge, TNG decreased the brain stem blood flow to a lesser extent than PGE1. However, the effects of isoflurane on all parameters were statistically identical in the three conditions not treated and pretreated with either vasodilator. Also, the blood concentrations of isoflurane did not differ among the three conditions. The present study demonstrates that isoflurane produces similar effects on systemic blood pressure, regional cerebral blood flow and sympathetic efferent discharge during vasodilator-induced hypotension and without any vasodilator.

Alprostadil↗

Vascular aldosterone in genetically hypertensive rats.

We have reported that aldosterone is synthesized and cytochrome P450aldo mRNA exists in the vasculature. To clarify the pathophysiological role of vascular aldosterone in hypertension, we compared aldosterone production in the mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats (WKY). The expressions of mRNA of cytochrome P450aldo, mineralocorticoid receptor, and alpha 1, Na,K-ATPase in the mesenteric arteries were compared between the two groups. Aldosterone concentration in the perfusate of the vasculature was measured by radioimmunoassay after purification with high-performance liquid chromatography. Cytochrome P450aldo and mineralocorticoid receptor mRNA levels were quantified by Southern blot analysis of the products of reverse-transcribed polymerase chain reaction. Levels of alpha 1 Na,K-ATPase mRNA were measured by Northern blot analysis. Vascular aldosterone and cytochrome P450aldo mRNA levels of 2-week-old SHRSP were significantly increased compared with those of age-matched WKY. However, vascular aldosterone in 4- and 9-week-old SHRSP did not differ from that in age-matched WKY. Expression levels of mineralocorticoid receptor mRNA in the vasculature of 4- and 9-week-old SHRSP were significantly increased compared with those in age-matched WKY. Concentrations of vascular alpha 1 Na,K-ATPase mRNA of 2-, 4-, and 9-week-old SHRSP also were significantly higher than those in age-matched WKY. These results suggest that vascular aldosterone contributes to the pathophysiology of hypertension in SHRSP in the early stage.

Aldosterone↗

Brain nitric oxide synthase messenger RNA in central mineralocorticoid hypertension.

The mechanism underlying the central hypertensinogenic effects of mineralocorticoids remains unclear. Given that nitric oxide (NO) is thought to act at autonomic sites in the brain to regulate arterial blood pressure, the effects of the potent mineralocorticoids aldosterone and 19-noraldosterone on the abundance of neuronal NO synthase (nNOS) mRNA in the brain were investigated. Wistar-Kyoto rats received a continuous intracerebroventricular infusion of aldosterone or 19-noraldosterone (5 ng/h) from an implanted osmotic minipump for 4 weeks. Total RNA was purified from microdissected tissue blocks containing the hypothalamus, dorsal medulla, rostral ventrolateral medulla, or caudal ventrolateral medulla, and changes in the abundance of nNOS mRNA were determined with a semiquantitative competitive polymerase chain reaction method. Blood pressure was significantly increased in rats 2, 3, and 4 weeks after the onset of intracerebroventricular aldosterone or 19-noraldosterone infusion compared with that in animals receiving vehicle. Subcutaneous infusion of either mineralocorticoid had no effect on blood pressure. Compared with controls, rats treated with aldosterone or 19-noraldosterone for 4 weeks showed significant decreases in the amount of nNOS mRNA in the hypothalamus and rostral and caudal ventrolateral medulla. These data suggest that reduced nNOS activity may contribute to the increase in blood pressure in rats with central mineralocorticoid-induced hypertension.

Aldosterone↗

A modified coaxial compound micropipette for extracellular iontophoresis and intracellular recording: fabrication, performance and theory.

Investigation of the identity and modes of action of neurotransmitters in the mammalian central nervous system can be facilitated by simultaneous intracellular recording of membrane potential and extracellular iontophoresis of agonists and antagonists. We describe here techniques for conveniently constructing a compound microelectrode, originally described by Sonnhof (Pflugers Arch 341, 351-358, 1973), suitable for such studies. The Sonnhof electrode consists of two components, a centraxial micropipette for recording membrane potential surrounded by a cylindrical array of 6 pipettes for iontophoresis. The cylindrical array tapers coaxially and terminates in 6 contiguous, crescent-shaped orifices surrounding the terminal portion of the central pipette, 25 - 50 microm from the tip. Pipettes were constructed from borosilicate glass tubing of 1-mm wall thickness having a 10-mm or 16-mm outer diameter. The resistances, flux and transport numbers for iontophoresis of glycine were measured for pipettes constructed from both sizes of glass. Flux increased with increasing levels of current, and transport number decreased with increasing micropipette resistance. A spherical diffusion model points out the steep dependence of steady state concentration on diffusional distance, stressing the importance of diminishing the distance between the iontophoresis source and the recording site. This is particularly true when brief pulses of current are used.

Animals↗

Pheochromocytoma in a long-term hemodialysis patient, discovered as an adrenal incidentaloma.

A case of pheochromocytoma was discovered incidentally during long-term hemodialysis for chronic renal failure due to acquired cystic kidney disease. A 52-year-old male patient was examined for weight loss of 3 kg during over a period of 3 months. Abdominal computed tomography (CT) revealed a left adrenal mass (3.0 cm in size). Plasma adrenaline and noradrenaline were increased to 521 pg/ml and 1,341 pg/ml, respectively, and the metoclopramide provocative test was positive. Further, in the scintiscan using 123I-metaiodobenzylguanidine (MIBG), an accumulation of the radionuclide in the left adrenal tumor region was confirmed. The patient is currently under observation and conservative treatment due to the possible occurrence of arterial hypotension after resection of the tumor and to lesser possibility of the malignancy.

3-Iodobenzylguanidine↗