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Biomedical subjects

R Hashimoto

Publications and source records attributed to R Hashimoto.

At least 37 records · Page 2Linked to original sources

Functional differentiation in the human auditory and language areas revealed by a dichotic listening task.

The human auditory cortex plays a special role in speech recognition. It is therefore necessary to clarify the functional roles of individual auditory areas. We applied functional magnetic resonance imaging (fMRI) to examine cortical responses to speech sounds, which were presented under the dichotic and diotic (binaural) listening conditions. We found two different response patterns in multiple auditory areas and language-related areas. In the auditory cortex, the medial portion of the secondary auditory area (A2), as well as a part of the planum temporale (PT) and the superior temporal gyrus and sulcus (ST), showed greater responses under the dichotic condition than under the diotic condition. This dichotic selectivity may reflect acoustic differences and attention-related factors such as spatial attention and selective attention to targets. In contrast, other parts of the auditory cortex showed comparable responses to the dichotic and diotic conditions. We found similar functional differentiation in the inferior frontal (IF) cortex. These results suggest that multiple auditory and language areas may play a pivotal role in integrating the functional differentiation for speech recognition.

Acoustic Stimulation↗

Surgical cryoablation for frequent premature ventricular contraction originating in the left sinus of Valsalva.

Cryoablation in the left ventricular outflow tract and aortic valve replacement were conducted in a 70-year-old man with frequent premature ventricular contraction and nonsustained ventricular tachycardia complicated by Sellers grade 4 aortic regurgitation. The earliest endocardial activation site during premature ventricular contraction was confirmed by a preoperative electrophysiological study of the left sinus of Valsalva. Cryoablation preceded valvulectomy followed by aortic valve replacement. Clinical symptoms of premature ventricular contraction disappeared immediately after surgery.

Aortic Valve↗

Progressive and sufficient decrease of hepatitis B core antibody can predict the disappearance of hepatitis B virus DNA in Japanese patients with hepatitis B surface antigen clearance.

The aim of this study was to elucidate the relationships among serum levels of hepatitis B virus (HBV) DNA, periods after hepatitis B surface (HBs) antigen clearance, and the titer of hepatitis B core (HBc) antibody in 200-fold diluted serum. Twelve patients who had clearance of HBs antigen from serum were studied. Five patients had not received any treatment (group A), and seven had received prednisolone withdrawal therapy. The patients in groups A and B were followed up for 86 months and 108 months (median), respectively. Serum HBV was measured by the nested polymerase chain reaction method. In both groups, serum HBV tended to become gradually undetectable after HBs antigen clearance. The positive rate of HBV in the sera 5 years or more after HBs antigen clearance was significantly lower than that in the sera at less than 5 years, both in group A (P = 0.004) and group B (P = 0.010). In both groups, the titer of HBs tended to decline every year after HBs antigen clearance. HBV was still detectable in the sera of some patients for a long period of time after they showed seroconversion to HBs antibody. The results suggest that detection of HBV was difficult in sera with an HBc titer of 30% or lower and at more than 5 years after HBs antigen clearance in both groups. It is important to note that HBV DNA rarely exists in the serum, even when HBs antigen and HBc are both negative.

Adolescent↗

Inhibition of radical reaction of apolipoprotein B-100 and alpha-tocopherol in human plasma by green tea catechins.

(-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), (-)-epigallocatechin gallate (EGCg), and Trolox inhibited the decreases of apolipoprotein B-100 (apoB) and alpha-tocopherol in a radical reaction of human plasma initiated by Cu(2+). The concentrations of EC, EGC, ECg, EGCg, and Trolox for 50% inhibition (IC50) of apoB fragmentation were 39.1, 42.2, 14.6, 21.3, and 36.2 microM, respectively. Similar IC50 values were observed for alpha-tocopherol consumption, indicating the close relationship between apoB fragmentation and alpha-tocopherol consumption. These results demonstrate that tea catechins serve as an effective antioxidant in plasma and that the gallate group has a strong antioxidative activity.

Antioxidants↗

Results of patch testing with lavender oil in Japan.

We report the annual results of patch testing with lavender oil for a 9-year period from 1990 to 1998 in Japan. Using Finn Chambers and Scanpor tape, we performed 2-day closed patch testing with lavender oil 20% pet. on the upper back of each patient suspected of having cosmetic contact dermatitis. We compared the frequency of positive patch tests to lavender oil each year with those to other fragrances. We diagnosed contact allergy when patch test reactions were + or <+ at 1 day after removal. The positivity rate of lavender oil was 3.7% (0-13.9%) during the 9-year period from 1990 to 1998. The positivity rate of lavender oil increased suddenly in 1997. Recently, in Japan, there has been a trend for aromatherapy using lavender oil. With this trend, placing dried lavender flowers in pillows, drawers, cabinets, or rooms has become a new fashion. We asked patients who showed a positive reaction to lavender oil about their use of dried lavender flowers. We confirmed the use of dried lavender flowers in 5 cases out of 11 positive cases in 1997 and 8 out of 15 positive cases in 1998. We concluded that the increase in patch test positivity rates to lavender oil in 1997 and 1998 was due to the above fashion, rather than due to fragrances in cosmetic products.

Adolescent↗

Localized phosphorylation of vimentin by rho-kinase in neuroblastoma N2a cells.

BACKGROUND: Vimentin, which is one of the intermediate filaments, is the major cytoskeletal component in developing neurones or neuroblastoma cells. Rho-associated kinase (Rho-kinase), is rich in neurones and is found downstream of Rho. It is involved in the agonist-induced neurite retraction of neuronal cells, and phosphorylates vimentin at Ser-38 and Ser-71 resulting in in vitro disassembly of the filaments. RESULTS: We have investigated the distribution of vimentin phosphorylated by Rho-kinase in N2a neuroblastoma cells using site-specific phosphorylation-dependent antibodies. TM71 immunoreactivity, which specifically indicates Ser-71 phosphorylation on vimentin, was found in some neurites of dibutyryl cAMP-differentiated N2a cells. Transfection of the constitutively active form of Rho-kinase, CAT, significantly elevated TM71 immunoreactivity, and induced neurite retraction or cell rounding. Conversely, transfection of the dominant negative form of Rho-kinase, RB/PH(TT), or treatment of 10 microM Y-27632, a Rho-kinase specific inhibitor, abolished TM71 immuno-reactivity, and induced irregular neurite outgrowth. In contrast, 20 nM okadaic acid (OA) induced neurite retraction and specifically elevated TM71 immunoreactivity. In the OA-induced neurite retraction, tubulin disappeared in retracting neurites, where vimentin and actin remained co-localized. Furthermore, the OA-induced elevation of TM71 immunoreactivity and neurite retraction were completely blocked by pretreatment with 10 microM Y-27632, or by the ectopic expression of RB/PH(TT). CONCLUSIONS: This study suggests that the localized phosphorylation of vimentin by Rho-kinase in neurites was closely related with the cellular morphology of N2a cells, and that the Rho-kinase activity towards vimentin was balanced with OA-sensitive phosphatases.

Amides↗

Tau protein is a potential biological marker for normal pressure hydrocephalus.

A biological marker for normal pressure hydrocephalus (NPH) is beneficial for evaluation of its severity and of indications for shunt operation. Tau protein was initially considered as a biological marker in cerebrospinal fluid (CSF) from Alzheimer's patients. Recently, it has been demonstrated that degeneration in the brain causes elevation of tau in CSF. Therefore, the tau level in CSF from NPH patients was evaluated. Tau levels in CSF from NPH patients were significantly higher than that in controls. The tau levels were correlated with the severity of dementia, urinary incontinence, and gait disturbance in NPH. These results suggest that CSF tau may be useful as a biological marker for NPH to determine the level of neuronal degeneration.

Aged↗

Major phosphorylation site (Ser55) of neurofilament L by cyclic AMP-dependent protein kinase in rat primary neuronal culture.

Ser55 of neurofilament L (NF-L) is reported to be partly phosphorylated in neurons and to be phosphorylated by cyclic AMP-dependent protein kinase (PKA). Bovine NF-L was phosphorylated by PKA in a low concentration of MgCl2 (0.3 mM) and digested by trypsin. Trypsin-digested fragments were assigned by MALDI/ TOF (matrix-assisted laser desorption and ionization/ time-of-flight) mass spectrometry. Phosphorylation sites were found at Ser41, Ser55, and Ser62 in the head region, with Ser55 considered the preferred site. A site-specific phosphorylation-dependent antibody against Ser55 rendered NF-L phosphorylated at Ser55 detectable in primary cultured rat neurons. One-hour treatment with 20 nM okadaic acid increased the phosphorylation level of Ser55, and co-treatment with 10 microM forskolin enhanced it. However, forskolin alone did not elevate the phosphorylation level. As a consequence, NF-L may be phosphorylated at Ser55 by PKA or by a PKA-like kinase in vivo; however, the phosphorylation level of Ser55 may be modulated by certain phosphatases sensitive to okadaic acid.

Amino Acid Sequence↗

Site-specific phosphorylation of neurofilament-L is mediated by calcium/calmodulin-dependent protein kinase II in the apical dendrites during long-term potentiation.

Neurofilament-L (NF-L), one subunit of the neuronal intermediate filaments, is a major element of neuronal cytoskeletons. The dynamics of NF-L are regulated by phosphorylation of its head domain. The phosphorylation sites of the NF-L head domain by protein kinase A, protein kinase C, and Rho-associated kinase have been previously identified, and those by calcium/calmodulin-dependent protein kinase II (CaMKII) were identified in this study. A series of site- and phosphorylation state-specific antibodies against NF-L was prepared to investigate NF-L phosphorylation in neuronal systems. Long-term potentiation (LTP) is a cellular model of neuronal plasticity that is thought to involve the phosphorylation of various proteins. NF-L is considered a possible substrate for phosphorylation. During LTP stimulation of mouse hippocampal slices, the series of antibodies demonstrated the increase in the phosphorylation level of Ser(57) in NF-L and the visualization of the localized distribution of Ser(57) phosphorylation in a subpopulation of apical dendrites of the pyramidal neurons. Furthermore, Ser(57) phosphorylation during LTP is suggested to be mediated by CaMKII. Here we show that NF-L is phosphorylated by CaMKII in a subpopulation of apical dendrites during LTP, indicating that Ser(57) is a novel phosphorylation site of NF-L in vivo related to the neuronal signal transduction.

Amino Acid Sequence↗

Quantitative blood velocity mapping in glomerular capillaries by in vivo observation with an intravital videomicroscope.

We have evaluated rat glomerular microcirculation under in-vivo condition with an intravital videomicroscope. To measure erythrocyte velocities, a line segment was set along the glomerular capillaries in time-sequential videotaped images and then a spatiotemporal image was constructed along that segment. The angle of striped pattern in the spatiotemporal image which reflects the erythrocyte velocity, was estimated to compute erythrocyte velocity vector mapping. We found that erythrocyte velocities in rat glomeruli were significantly faster in diabetic rats than in control rats (p < 0.05). In conclusion, we have succeeded in quantitatively evaluating the in-vivo renal microcirculation with our videomicroscope system and by spatiotemporal image analyzing method.

Animals↗

Direct in vivo visualization of glomerular microcirculation by intravital pencil lens-probe CCD videomicroscopy.

There have been developed several types of experimental techniques for evaluation of renal microcirculation. Although each methodology possesses excellent and unique characteristics, it requires substantial artificial manipulation that might alter the renal microvascular responsiveness. To circumvent such limitations of previous ex vivo or in vitro approaches to glomerular microcirculation, we have developed a pencil lens probe CCD intravital videomicroscopic system that allows us to evaluate both systemic hemodynamics and renal microcirculation. Furthermore, real time images of afferent and efferent arterioles as well as glomeruli can be continuously assessed, which would facilitate the functional characterization of these microvessels in vivo. Finally, the tapered nature of the CCD probe of this videomicroscopy may allow direct observation of the renal microvasculature in small animals. In conclusion, this novel technique is a valuable tool for unveiling the in vivo, in situ, and intact renal microvascular behavior, and may provide further approaches to the understanding of renal microcirculation.

Animals↗

Distribution of Rho-kinase in the bovine brain.

Rho-associated kinase (Rho-kinase) is a serine/threonine protein kinase downstream of the small GTPase Rho, which participates in signaling pathways of many cellular functions. Although Rho-kinase is implicated in the regulation of the morphology of neuronal cells, the distribution of Rho-kinase in the brain has not been elucidated yet. In this study, we investigated the distribution of Rho-kinase using three antibodies recognizing the different epitopes of Rho-kinase. Rho-kinase was abundantly expressed in the gray matter in comparison with the white matter. Strong immunoreactivity was observed in the pyramidal neurons of the cerebral cortex and hippocampus and in the Purkinje cells of the cerebellum. These results indicate that Rho-kinase is abundantly distributed in neurons and might play an important role in remodeling of neurites.

Animals↗

Postencephalitic focal retrograde amnesia after bilateral anterior temporal lobe damage.

BACKGROUND: Marked retrograde amnesia with no or almost no anterograde amnesia is rare. Recently, a combination of ventrolateral prefrontal and temporopolar cortical lesions has been suggested as the cause of such isolated or focal retrograde amnesia. It is also assumed that when the right-sided cortical structures are damaged, autobiographical episodic memories are affected. OBJECTIVE: To search for new anatomic substrates for focal retrograde amnesia. METHODS: We performed extensive neuropsychological tests and obtained detailed neuroimages on a 43-year-old woman who showed a severe, persistent retrograde amnesia but only a limited anterograde amnesia after probable herpes simplex encephalitis. RESULTS: Tests of autobiographical memory revealed that she had a memory loss extending back to her childhood for both semantics and incidents; however, the ability to recall specific episodes appeared much more severely impaired than the ability to recall factual information about her past. The patient also showed profound impairments in recalling public memories; however, her scores improved nearly to a control level on forced-choice recognition memory tasks, although the recall of memories for a decade just before her illness remained mildly impaired. MRI revealed focal pathologies in the temporal poles and the anterior parts of the inferotemporal lobes on both sides, predominantly on the left, with some extension to the anterior parts of the medial temporal lobes. There was additional damage to the left insular cortex and its surrounding structures but no evidence of frontal lobe damage on MRIs or cognitive tests. CONCLUSIONS: A profound retrograde amnesia may be produced by damage to the bilateral temporal poles and anterior inferotemporal lobes in the absence of frontal lobe pathologies, and a dense and persistent episodic old memory loss can arise even with a relatively small lesion in the right anterior temporal lobe if it is combined with extensive damage to the left.

Adult↗

Casein kinase II is responsible for phosphorylation of NF-L at Ser-473.

Ser-473 is solely phosphorylated in vivo in the tail region of neurofilament L (NF-L). With peptides including the native phosphorylation site, it was not possible to locate responsible kinases. We therefore adopted full-length dephosphorylated NF-L as the substrate, and employed MALDI/TOF (matrix-assisted laser desorption and ionization/time of flight) mass spectrometry and a site-specific phosphorylation-dependent antibody recognizing Ser-473 phosphorylation. The antibody showed that casein kinase I (CK I) as well as casein kinase II (CK II) phosphorylated Ser-473 in vitro, while neither GSK-3beta nor calcium/calmodulin-dependent protein kinase II did so. However, the mass spectra of the tail fragments of the phosphorylated NF-L indicated that CK II was the kinase mediating Ser-473 phosphorylation in vitro as opposed to CK I, because CK I phosphorylated another site as well as Ser-473 in vitro. The antibody also demonstrated that NF-L phosphorylated at Ser-473 was abundant in the neuronal perikarya of the rat cortex, indicating that phosphorylation of Ser-473 may take place there. This result may support the suggestion that CK II is the kinase responsible for Ser-473 phosphorylation. Despite many reports showing that CK I mediates phosphorylation of neurofilaments, CK II may phosphorylate NF-L in vivo.

Amino Acid Sequence↗

Dynamic changes in corticospinal excitability during motor imagery.

We investigated temporal changes in the amplitudes of motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation over the left motor cortex during motor imagery. Nine subjects were instructed to imagine repetitive wrist flexion and extension movements at 1 Hz, in which the flexion timing was cued by a tone signal. Electromyographs (EMGs) were recorded from the first dorsal interosseous, flexor carpi radialis and extensor carpi radialis muscles of the right hand, and magnetic stimulation was delivered at 0, 250, 500 and 750 ms after the auditory cue. On average, the evoked EMG responses were larger in the flexor muscle during the phase of imagined flexion than during extension, whilst the opposite was true for the extensor muscle. There were no consistent changes in the amplitudes of MEPs in the intrinsic hand muscle (first dorsal interosseous). The EMG remained relaxed in all muscles and did not show any significant temporal changes during the test. The H-reflex in the flexor muscle was obtained in four subjects. There was no change in its amplitude during motor imagery. These observations lead us to suggest that motor imagery can have dynamic effects on the excitability of motor cortex similar to those seen during actual motor performance.

Adult↗

Presenilin-2 mutation and polymorphism in Japanese Alzheimer disease patients.

The Asn141Ile mutation of the presenilin 2 gene is responsible for familial early-onset Alzheimer disease found in Volga-German kindreds. However, the genetic influence of presenilin 2 gene on sporadic Alzheimer disease remains unknown. In this study, the frequency of the mutation and genetic association with the presenilin 2 locus were investigated in Japanese sporadic cases. The Asn141Ile mutation was not found in 88 cases of sporadic Alzheimer disease or 13 unrelated cases of familial Alzheimer disease. Fifty cases of late onset sporadic Alzheimer disease and 50 age-matched controls indicated no association with an exon 3 polymorphism of the presenilin 2 gene. These results indicate that the presenilin 2 mutation is not a major cause of Alzheimer disease.

Age of Onset↗