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Biomedical subjects

T Yonezawa

Publications and source records attributed to T Yonezawa.

At least 37 records · Page 2Linked to original sources

Signal transduction cascade in staurosporine-induced prostaglandin E(2) production by rat peritoneal macrophages.

The possible participation of phosphatidylinositol (PI) 3-kinase, p44/42 mitogen-activated protein (MAP) kinases and protein kinase C (PKC) in staurosporine-induced prostaglandin E(2) (PGE(2)) production was investigated pharmacologically in rat peritoneal macrophages. When the cells were incubated in the presence of staurosporine (63 nM), phosphorylation of p44/42 MAP kinases and cytosolic phospholipase A(2) (cPLA(2)) was induced at 15 min and increased until 60 min, whereas PGE(2) production and expression of cyclooxygenase-2 (COX-2) protein began to increase at 2 h and increased thereafter. Both PD98059 and U0126, MAP kinase/extracellular signal-regulated kinase (ERK) kinase inhibitors, and LY294002, a PI 3-kinase inhibitor, inhibited staurosporine-induced phosphorylation of p44/42 MAP kinases and cPLA(2) and PGE(2) production. Moreover, U0126 inhibited staurosporine-induced arachidonic acid release at 1 h. Although PD98059 and U0126 at 30 microM partially inhibited staurosporine-induced COX-2 protein expression, they completely inhibited staurosporine-induced PGE(2) production. LY294002 at 100 microM did not inhibit staurosporine-induced expression of COX-2 protein. In contrast, Ro-31-8220, a PKC inhibitor, completely inhibited staurosporine-induced PGE(2) production and COX-2 protein expression at 8 h but did not inhibit staurosporine-induced phosphorylation of p44/42 MAP kinases and cPLA(2). These findings suggest that staurosporine induces PGE(2) production by two mechanisms. One is cPLA(2) phosphorylation through a signal transduction pathway from PI 3-kinase to p44/42 MAP kinases, by which arachidonic acid, a substrate for COX-1 and COX-2, is increased. The other is COX-2 protein expression, which is induced mainly by activation of PKC and partially by activation of p44/42 MAP kinases; thus, arachidonic acid is metabolized to PGE(2).

Animals↗

[A surgical case of papillary muscle reconstruction and double-CABGs for mitral regurgitation due to ruptured papillary muscle after myocardial infarction].

A 76-year-old female patient underwent papillary muscle reconstruction, and d-CABGs a month after the onset of myocardial infarction. Posterior papillary muscle (PPM) was recognized to be ruptured partially, its stump was sewn to original PPM. An ePTFE suture (CV 5) was placed from anterior mitral leaflet to anterior papillary muscle in attempt to reinforce PPM-repair. Carpentier-Edwards ring was inserted and d-CABGs (LITA to LAD and GEA to RCA) were performed, simultaneously. Postoperative examination revealed no regurgitation and no stenosis of bypass grafts during follow-up period of 5 months after the procedure. Papillary muscle reconstruction was effective procedure for MR due to the ruptured papillary muscle.

Aged↗

Dielectric analysis for estimation of oil content in the mycelia of Mortierella alpina.

The dielectric behavior of the filamentous fungi Mortierella alpina SAM2104 and 1S-4, which produce polyunsaturated fatty acid enriched oil in the mycelia, was investigated. During the cultivation carried out in a 10-kL fermentor for 12-15 days, the relative permittivity and conductivity of the broth were measured in the frequency range of 100 kHz to 30 MHz. The dielectric parameters, i.e., the amplitude of dielectric relaxation (Deltaepsilon) and the characteristic frequency (f(c)), were obtained by fitting the Cole-Cole equation to the observed dielectric relaxation, and the conductivity of the medium (kappa(a)) was also measured. The value of Deltaepsilon gradually increased from the second day through the end of cultivation, suggesting that volume fraction of the cell increased with oil accumulation. The conductivity of the cytoplasm (kappa(i)) was calculated from the experimental values of f(c) and kappa(a), using a theoretical equation based on an ellipsoidal cell model. As a result, good correlation between the calculated kappa(i) and the oil content was obtained. These findings indicate that dielectric analysis enables us to estimate the oil content in the mycelia of oleaginous fungi and also provides a useful tool for monitoring cell growth and for controlling the cultivation process.

Bioreactors↗

In vivo intradiscal pressure measurement in healthy individuals and in patients with ongoing back problems.

STUDY DESIGN: In vivo intradiscal pressure measurement in different postures in healthy individuals and in those with ongoing back problems. OBJECTIVES: With the most recent technique, 1) to analyze the influence of degeneration on the intradiscal pressure, 2) to calculate the spinal load on the L4-L5 intervertebral discs, and 3) to assess the relation between the spinal load and movement of the intervertebral motion segment. SUMMARY OF BACKGROUND DATA: Almost all the data on intradiscal pressure are from the studies by Nachemson. The results from these pioneering studies have formed the basis for current knowledge about the in vivo loading conditions of the human spine. Although performed already during the 1960s and 1970s with the technique available at that time, virtually no other similar studies have been performed to corroborate the findings. METHODS: The intradiscal pressure (vertical and horizontal) was measured using an advanced pressure sensor in 8 healthy volunteers and 28 patients with ongoing low back pain, sciatica, or both at L4-L5. Among other calculations, the actual loading conditions in various body positions were calculated in relation to the angle between the two vertebrae of the studied motion segments. RESULTS: The effect of respiration on intradiscal pressure was shown as a continuously periodic fluctuation in the healthy prone individual. The intradiscal pressure was significantly reduced according to the degree of disc degeneration as estimated by magnetic resonance imaging. There possibly was a difference between the vertical and horizontal pressures in the degenerated and nondegenerated discs because the nucleus pulposus was pressure-tropic property. The spinal load increased in the following order of body positions: prone, 144 N; lateral, 240 N; upright standing, 800 N; and upright sitting, 996N (P < 0.0001). In the standing and sitting body positions, the spinal load increased not only with forward bending, but also with backward bending. The spinal load was highly dependent on the angulation in the motion segment. The movements of the spine from a flexed to an extended position made the load of the spine change in a curvilinear fashion, fitting a squared equation in the standing body position. There was a correlation between the spinal load and the angle of the motion segment in the standing but not in the sitting body position. CONCLUSIONS: The spinal load was highly dependent on the angle of the motion segment in normal discs in vivo. The intradiscal pressure in degenerated discs was significantly reduced compared with that of normal discs. However, further studies on the effect of respiratory movement on intradiscal pressure, the difference between vertical and the horizontal pressures, and the difference in the spinal load between standing and the sitting body positions are necessary. The data obtained from the current study are fundamental to understanding the pathomechanisms and biomechanical problems of disc disease.

Adult↗

Real-time monitoring of yeast cell division by dielectric spectroscopy.

To assay cell cycle progression in synchronized culture of yeast we have applied dielectric spectroscopy to its real-time monitoring. The dielectric monitoring is based on the electromagnetic induction method, regarded as a nonelectrode method, which has resolved the problems encountered in measurements with metal electrodes, namely electrode polarization and bubble formation on electrodes. In the synchronized culture with temperature-sensitive cell division cycle mutants, the permittivity of the culture broth showed cyclic changes at frequencies below 300 kHz. The increase and decrease in the cyclic changes of the relative permittivity correspond to the increase in cell length and bud size and to the septum formation between mother and daughter cells, respectively.

Biophysical Phenomena↗

The autonomic control of the transmural dispersion of ventricular repolarization in anesthetized dogs.

INTRODUCTION: The initiation of ventricular arrhythmias is in part associated with autonomic nervous tone. We investigated the effects of sympathetic and parasympathetic stimulation on the monophasic action potentials (MAPs) of the epicardium (EPi), mid-myocardial (M) region, and endocardium (Endo) in vivo. METHODS AND RESULTS: In 12 mongrel open chest anesthetized dogs, both sides of the cervical vagus nerves and stellate ganglia were crushed with a tight ligature. Right atrial pacing at 600 msec cycle length was begun after the sinus nodal area had been crushed. MAPs from the M region were measured by two needle electrodes that were supported by a W-shaped plastic frame. The epicardial, M region, and endocardial MAP durations at 90% repolarization (MAPD90) were 287+/-7, 315+/-7, and 290+/-8 msec, respectively. The MAPD90 from M cells was longer than that from Epi or Endo. Sympathetic stimulation shortened MAPD90 more in the M region (53+/-4 msec) than that in the Epi (27+/-3 msec) or Endo (26+/-4 msec). The transmural dispersion of repolarization during sympathetic stimulation was shorter than that of the control. Parasympathetic stimulation did not significantly affect any of the MAPD90 values. Simultaneous sympathetic and parasympathetic stimulation produced changes not significantly to those produced by sympathetic stimulation alone. CONCLUSION: Our results suggest that sympathetic activity can reduce transmural dispersion of repolarization under autonomic control in the canine heart under baseline conditions.

Action Potentials↗

Angiotensin II type 1 receptor antagonist downregulates nonmuscle myosin heavy chains in spontaneously hypertensive rat aorta.

The aim of this study was to clarify the differences between the angiotensin II type 1 (AT1) receptor antagonist and the angiotensin-converting enzyme (ACE) inhibitor on smooth muscle and nonmuscle myosin heavy chain isoforms in aortic smooth muscle cells of Wistar-Kyoto rats and spontaneously hypertensive rats. All 4 myosin heavy chain isoforms are heterogeneously expressed in the smooth muscle cells of the aortic tunica media in 20-week-old rats, and the contractile-type myosin heavy chains are highly expressed in smooth muscle cells of the aortic tunica media compared with the synthetic-type myosin heavy chains. Both the AT1 receptor antagonist and the ACE inhibitor had the same effects on hemodynamics, smooth muscle cell hypertrophy and proliferation, fibrosis, and vascular remodeling in spontaneously hypertensive rats. However, the AT1 receptor antagonist had a more potent effect on the downregulation of the synthetic-type myosin heavy chains than the ACE inhibitor in spontaneously hypertensive rat aortic tunica media. In contrast, these effects of the AT1 receptor antagonist and the ACE inhibitor on hemodynamics, morphology, fibrosis, and expression of myosin heavy chain isoforms in smooth muscle cells of the aortic tunica media were not observed in Wistar-Kyoto rats. Thus, within 6 weeks, the AT1 receptor antagonist might modulate the cellular composition of myosin heavy chain isoforms in smooth muscle cells more efficiently than the ACE inhibitor, without morphological changes in the spontaneously hypertensive rat aorta.

Angiotensin Receptor Antagonists↗

Reduced urination rate while drinking beer with an unpleasant taste and off-flavor.

A lowered subjective evaluation of the taste and flavor of beer due to staleness or to the addition of an unpleasant taste and flavor was found to be closely correlated with the urination rate. Beer in the same lot was compared immediately after shipment from the brewery and after leaving at room temperature for 1 month or 5 months. Each beer sample was given to volunteers at the rate of 3 ml/kg/15 min for 2 hours, and the urine volume was measured every 30 minutes. The urination rate was highest from the volunteers who drank fresh beer and lowest from those who drank 5-month-old beer. The subjective evaluation of both the taste and drinkability of 5-month-old beer was significantly lower than that of fresh beer. Beer samples with various unpleasant taste and flavor substances added lowered the urination rate. The results suggest that the perception of an unpleasant taste and off-flavor would lower the urination rate.

Adult↗

[Dorsal root identification using spinal endoscopy and electro-physiology].

We aimed to develop a method of accurately identifying the dorsal root for the corresponding peripheral afferent nerve under endoscopic observation. We developed an endoscope with an external diameter of 1.8 mm. After small laminectomy on the lower thoracic vertebrae, we inserted this endoscope carefully into the epidural and then subarachnoid spaces. We observed structures in these spaces with the endoscope. We tried to determine the spatial relationship between these electrodes and dorsal root. After identifying each space, we inserted two electrodes into the visualized space to record evoked potentials; a bipolar electrode (protocol 1) and a catheter-type eight polar electrode (protocol 2). Each pole could be distinguished by marks. To stimulate peripheral nerves, we inserted needle-type electrodes into Th 10, 11 and 12 intercostal nerves. We attempted to record potentials from dorsal surface of the cord generated by intercostal nerve stimulus. Protocol 1: We moved the position of the bipolar recording electrodes between Th 9 and L 1 by 1 cm increment, and obtained evoked potentials correspondingly. Protocol 2: We chose the neighboring pairs of poles sequentially from the tip of the catheter for bipolar recording. At the end of each experiment, we dissected the animal and checked the intercostal nerve originating from the root. With the endoscope, we could clearly observe structures in the epidural and subarachnoid spaces. We could record evoked potentials from the dorsal spinal cord with the electrodes located either in epidural or in subarachnoid spaces. Shapes of evoked potentials changed characteristically according to the relative position between the root and the electrode. The largest potentials were obtained when the electrode was nearest to the dorsal root, of which the peripheral nerve was being stimulated. By combining endoscopy with the electrophysiological technique, we could accurately identify the dorsal roots for the corresponding peripheral afferent nerves. This method may be used for the selective dorsal root blockade under the visual field.

Animals↗

[Serial change of cerebral blood flow after collagenase induced intracerebral hemorrhage in rats].

In case of intracerebral hemorrhage (ICH), many clinical studies have reported that great alterations in regional cerebral blood flow (rCBF) have been observed not only in the acute but also in the chronic stage. However, due to the absence of reproducible animal model, experimental studies have failed to confirm the evidence. We therefore studied the serial change of rCBF and investigated the possibility of secondary brain damage using our collagenase induced ICH model. A total of 60 adult male rats were examined. 2 microliters artificial cerebrospinal fluid, which was adjusted to a pH 7.4 by a buffer, containing 0.25 units of bacterial collagenase was stereotactically injected into the left caudoputamen in 28 rats. 2 microliters artificial cerebrospinal fluid without collagenase was also injected into 28 control rats under sham operation. The remaining 4 rats were studied as a non treatment group. The rCBF of the frontal cortex, parietal cortex, temporal cortex, occipital cortex, caudoputamen, thalamus and the cerebellum was determined bilaterally by [14C]-iodoantipyrine quantitative autoradiography according to Sakurada's method at 2, 4, 12, 24, 48, 168 and 720 hours after the operation. At 4 hours after injection, significant decrease of rCBF was observed in the ipsilateral hemisphere and also in some contralateral regions. In the ipsilateral frontal cortex and caudoputamen, there was significant increase of the rCBF which reached close to the baseline at 24 hours. After that, the rCBF of those regions decreased significantly again and remained at a low value even 1 month after injection. In the other regions of the ipsilateral hemisphere which were located remotedly from the hematoma, the rCBF recovered from 24 to 48 hours after injection. In the contralateral hemisphere, the rCBF also recovered at 24 hours. We suggest that this alteration of the rCBF observed in perihematomatous regions was the result of secondary brain damage caused by the existence of hematoma. On account of this, we conclude that early removal of hematoma is necessary to obtain a better result in cases of ICH.

Animals↗

Cloning and expression of a unique inorganic pyrophosphatase from Bacillus subtilis: evidence for a new family of enzymes.

An open reading frame located in the COTF-TETB intergenic region of Bacillus subtilis was cloned and expressed in Escherichia coli and shown to encode inorganic pyrophosphatase (PPase). The isolated enzyme is Mn2+-activated, like the authentic PPase isolated from B. subtilis. Although 13 functionally important active site residues are conserved in all 31 soluble PPase sequences so far identified, only two of them are conserved in B. subtilis PPase. This suggests that B. subtilis PPase represents a new family of soluble PPases (a Bs family), putative members of which were found in Archaeoglobus fulgidus, Methanococcus jannaschii, Streptococcus mutans and Streptococcus gordonii.

Amino Acid Sequence↗

Dielectric behavior of budding yeast in cell separation.

Dielectric behavior of budding yeast in cell separation was studied by comparing two types of temperature-sensitive cell division cycle mutants that arrest before and after cell separation at the restrictive temperature. Single spherical cells before budding but after cell separation showed one main dielectric dispersion (centered at about 1 MHz) and one additional dielectric dispersion (at about 20 MHz), which were the Maxwell-Wagner dispersions due to the plasma membrane and due to both of the cell wall and vacuole, respectively. With cells that accumulated as doublets at a point immediately before cell separation, one more dielectric dispersion appeared around 200 kHz in addition to two dielectric dispersions similar to those found for the single cells without bud. The difference in dielectric behavior between the two types of cells might be mainly attributed to the difference in cell shape, which was theoretically examined using non-spherical cell models.

Cell Cycle↗

Dural arteriovenous malformation of the anterior cranial fossa occurring after bifrontal craniotomy.

A case of dural arteriovenous malformation of the anterior cranial fossa developing after bifrontal craniotomy is reported. The nidus was fed mainly by the left anterior ethmoidal artery. It was drained into the right sylvian vein and superior ophthalmic vein with patency of the superior sagittal sinus. A left frontal hemorrhage resulted from the nidus itself. This is the first reported case of an acquired dural arteriovenous malformation of the anterior cranial fossa verified by angiography. This rare lesion is discussed with regard to its etiology.

Cerebral Angiography↗

Physiological control of a total artificial heart: conductance- and arterial pressure-based control.

To obtain a physiological response by a total artificial heart (TAH), while eliminating the hemodynamic abnormalities commonly observed with its use, we proposed the use of a conductance- and arterial pressure-based method (1/R control) to determine TAH cardiac output. In this study, we endeavored to make use of a variable more closely tied to central nervous system (CNS) efferents, systemic conductance, to provide the CNS with more direct control over the output of the TAH. The control equation that calculates the target cardiac output of the TAH was constructed on the basis of measurement of blood pressures and TAH flow. The 1/R control method was tested in TAH-recipient goats with an automatic method by using a microcomputer. In 1/R control animals, the typical TAH pathologies, such as mild arterial hypertension and substantial systemic venous hypertension, did not occur. Cardiac output varied according to daily activity level and exercise in a manner similar to that observed in natural heart goats. These results indicate that we have determined a control method for the TAH that avoids hemodynamic abnormalities exhibited by other TAH control systems and that exhibits physiological responses to exercise and daily activities under the conditions tested. The stability of the control and the complete lack of inappropriate excursions in cardiac output is suggestive of CNS involvement in stabilizing the system.

Animals↗

Inhibition of delayed rectifier K+ current by dofetilide and E-4031 differentially affects electrical cardiac responses to vagus stimulation in anesthetized dogs.

Vagal activation influences various cardiac functions as well as occurrence of arrhythmias. Inhibition of a rapid type of delayed rectifier K+ current (I[Kr]) has been reported to be effective for the treatment of both ventricular and supraventricular arrhythmias. However, it is unknown how I[Kr] inhibition modulates the cardiac responses to vagal activation in situ. We analyzed the effects of I[Kr] inhibitors, dofetilide and E-4031, and a class I antiarrhythmic agent, disopyramide, on electrical cardiac responses to vagus stimulation in anesthetized dogs. Dofetilide (0.003-0.3 micromol/kg, i.v.), E-4031 (0.01-1 micromol/kg, i.v.) and disopyramide (2.9-29 micromol/kg, i.v.) prolonged sinus cycle length (SCL), right atrial effective refractory period (AERP) and ventricular effective refractory period (VERP) dose-dependently. During cervical vagus stimulation-induced prolongation of SCL, atrio-His (AH) interval and VERP and shortening of AERP, dofetilide and E-4031 inhibited the prolongation of SCL but potentiated the shortening of AERP. Dofetilide and E-4031 did not affect prolongations of AH interval and VERP. On the other hand, disopyramide inhibited all electrical cardiac responses to vagus stimulation. These results suggest that I(Kr) inhibition differentially modulate cardiac responses to vagus activation probably due to a different role of I(Kr) in each cardiac function in the heart in situ.

Animals↗

Different chronotropic and inotropic effects of EMD 57033 and EMD 53998, Ca2+ sensitizers, on isolated, blood-perfused dog heart preparations.

To investigate whether a Ca2+ sensitizer increases sinus rate, we studied the effects of racemic thiadiazinone, EMD 53998 (a Ca2+ sensitizer with phosphodiesterase inhibitory action) and its (+)-enantiomer EMD 57033 (a relatively pure Ca2+ sensitizer) on isolated, blood-perfused spontaneously beating right atria and paced left ventricles of the dogs. EMD 53998 increased sinus rate dose-dependently, but EMD 57033 did not. Both substances increased atrial and ventricular contractile force. Propranolol did not affect the responses to each substance. These results suggest that the Ca2+ sensitizing action induced by EMD 57033 does not affect pacemaker currents directly.

Animals↗