Biomedical subjects

K Hashimoto

Publications and source records attributed to K Hashimoto.

At least 91 records · Page 5Linked to original sources

PubMed2000

Aortic valve replacement with concomitant annular enlargement for small aortic annulus of less than 19 mm.

Three female patients with aortic stenosis associated with a severely small annulus underwent aortic valve replacement. In intraoperative measurements, a 19-mm obtulator could not pass through the aortic annulus in each case. We therefore concluded that it would be difficult to implant an appropriate-sized prosthesis in a routine fashion, so we performed an annular enlargement in a modified Nicks procedure. By using a wide teardrop-shaped patch for enlargement and slightly tilting insertion of a prosthesis, a 21 mm bileaflet mechanical prosthesis could be inserted into the enlarged annulus. Despite being a simpler method than other enlarging procedures, a two- or three-sizes larger prosthesis than the native annulus can be inserted with relative ease. Thus, the use of a 19 mm mechanical prosthesis may be avoidable in most adult cases.

Aged↗

PubMed2000

[Intrasellar epidermoid cyst].

We report a rare case of intrasellar epidermoid cyst. A 61-year-old man presented with complaints of the disturbance of consciousness and general fatigability. His laboratory data showed panhypopituitarism and MRI revealed the cystic tumor located at the intrasellar region. Tumor was removed by transsphenoidal approach and histological examination of the surgical specimen showed that the cyst wall was composed of the stratified squamous epithelium with keratohyaline granules.

Brain Diseases↗

PubMed2000

[A study of the minimum number of slices required for quantification of pulmonary emphysema by computed tomography].

We attempted to determine the minimum number of slices required for quantification of overall emphysema by computed tomography (CT). Forty-nine patients underwent CT scanning with a 15-mm slice interval, and 13 to 18 slices per patient were obtained. The percentage of low attenuation area (LAA%) per slice was measured with a method that we reported on previously, utilizing a CT program and NIH image. The average LAA% values for 1, 2, 3, and 6 slices evenly spaced through the lungs [LAA% (1), LAA% (2), LAA% (3), and LAA% (6)] were compared with those for all slices [LAA% (All)]. The correlation coefficients for LAA% (1), LAA% (2), LAA% (3), and LAA% (6) with LAA% (All) were 0.961, 0.981, 0.993, and 0.997, respectively. Mean differences +/- SD were -3.20 +/- 4.21%, -2.32 +/- 3.00, -0.20 +/- 1.84, and -0.16 +/- 1.26, respectively. From these results, we concluded that overall emphysema can be quantified by using at least three slices: one each of the upper, middle, and lower lung.

Adult↗

PubMed1999

Psychological stress increased corticotropin-releasing hormone mRNA and content in the central nucleus of the amygdala but not in the hypothalamic paraventricular nucleus in the rat.

The central administration of corticotropin-releasing hormone (CRH) to experimental animals sets into motion a coordinated series of physiological and behavioral events that promote survival during threatening situation. A large body of evidence suggest that CRH in the central nucleus of the amygdala (CEA) induces fear-related behaviors and is essential to fear conditioning; however, evidence of CRH-mediated activation of the amygdala under physiological situation is still limited. We report here a study of the impact of a psychological stressor on hypothalamic and amygdala CRH systems in the rat. Non-footshocked rats placed in a floored compartment surrounded by footshocked rats were defined as the psychological stress group. Rats were exposed to psychological stress for 15 min, and then sacrificed 1.5 and 3 h after cessation of stress. We found that our psychological stressor induced an increase in both CRH mRNA levels, as assessed by in situ hybridization histochemistry, and CRH content, as assessed by micropunch RIA, in the CEA. Exposure to the psychological stressor also caused a significant increase in CRH mRNA levels with a trend for an increase in CRH content in the dorsolateral subdivision of the bed nucleus of the stria terminalis (BNST) which is anatomically associated with the CEA. In contrast, psychological stress induced a small, but significant increase in type-1 CRH receptor (CRHR-1) mRNA in the hypothalamic paraventricular nucleus (PVN), while it failed to elevate either PVN CRH mRNA levels or content, CRH content in the median eminence (ME), or levels of plasma ACTH or corticosterone (CORT). Thus, in the context of a psychological stressor, the activation of the amygdala CRH system can occur without robust activation of the hypothalamic CRH system. In the light of previous data that the psychological stress-induced loss of sleep was reversed by the central administration of a CRH antagonist, these data suggest that CRH in the CEA may contribute to the psychological stress-evoked fear-related behavior such as hyperarousal. These data also indicate that in response to a psychological stressor, the amygdala CRH system is much more sensitive than is the CRH system emanating from the PVN.

Adrenocorticotropic Hormone↗

PubMed1999

Porphyrin-like fluorescence in oral cancer: In vivo fluorescence spectral characterization of lesions by use of a near-ultraviolet excited autofluorescence diagnosis system and separation of fluorescent extracts by capillary electrophoresis.

BACKGROUND: Red fluorescence from malignant tumors was observed in experimentally induced rat sarcoma by Policard (1924) and in ulcerated human oral carcinoma by Harris et al. (1987) by examination with ultraviolet (UV) irradiation. The objective of the current study was twofold: to examine in vivo the spectral characteristics of red fluorescence emitted from oral carcinomas and to separate the red fluorescent compounds in these lesions by the capillary electrophoretic (CE) method. METHODS: In vivo fluorescence spectral characteristics of oral carcinoma were examined by a near-UV excited autofluorescence diagnosis (NEAD) system developed by the authors. Fluorescence spectra of the extract from carcinomas were measured using a spectrofluorometer. CE was used to separate fluorescent compounds from the oral carcinomas. RESULTS: Of the 78 oral carcinomas examined using the NEAD system, 66 carcinomas (85%), including 2 adenoid cystic carcinomas (ACCs) and 14 recurrent squamous cell carcinomas (SCCs), showed porphyrin-like fluorescence spectra. The CE study was performed on three oral SCCs, two of which contained fluorescent compounds other than protoporphyrin IX and zinc protoporphyrin IX, whereas the other SCCs contained the compounds with the same migration time as protoporphyrin IX. CONCLUSIONS: Seventy-eight oral carcinomas, including ACCs and recurrent SCCs, were examined using the NEAD system. When exposed to UV light at a wavelength of 410 nm, 85% of the carcinomas showed porphyrin-like fluorescence spectra, whereas the normal mucosa in the oral cavity did not. Porphyrin-like fluorescent compounds were extracted from oral carcinomas and separated by a CE system equipped with a fluorescence detector. The CE data clearly show that compounds vary in each individual carcinoma.

Aged↗

PubMed1999

RNA melanoma vaccine: induction of antitumor immunity by human glycoprotein 100 mRNA immunization.

An RNA melanoma vaccine was investigated to induce protective immunity in a mouse-melanoma model. LacZ mRNA was synthesized in vitro by pSFV3 expression vector and introduced into the spleen of mice, using HVJ-liposomes. A high level of beta-galactosidase activity was detected for 10 days in mouse spleen. The human melanoma-associated antigen gp100 mRNA was synthesized in vitro by pSFV3 vector and encapsulated in HVJ-liposomes. Immunization by direct injection of the gp100 mRNA HVJ-liposomes into mouse spleen induced both anti-gp100 Ab and CTL responses against B16 melanoma. Immunization by administration of gp100 mRNA into the spleen delayed tumor growth and significantly prolonged survival compared with control treated mice. These preclinical studies demonstrate that an RNA tumor antigen vaccine strategy has potential application for human cancer treatment and prevention.

Animals↗

PubMed1999

Increased expression of zif268 mRNA in rat retrosplenial cortex following administration of phencyclidine.

Phencyclidine (PCP) has been shown to cause neurotoxicity in rat retrosplenial cortex following a single administration, although the precise mechanism underlying PCP-induced neurotoxicity is unclear. Using in situ hybridization and immunohistochemistry, we studied the effects of PCP on expression of immediate early gene zif268 mRNA and zif268 protein in the rat brain. High constitutive levels of zif268 mRNA and zif268 immunoreactivity were observed in the brain of control rats. Administration of PCP (12.5, 25 or 50 mg/kg, i.p., 6 h) caused marked induction of zif268 mRNA in the rat retrosplenial cortex, in a dose-dependent manner. However, the basal levels of zif268 mRNA in the other regions of cerebral cortex were decreased by administration of PCP. Emulsion-autoradiographical study suggested that marked expression of zif268 mRNA was observed in the layers III and IV of retrosplenial cortex where the neurotoxicity of PCP was detected. Furthermore, zif268 immunoreactivity in the layer IV of retrosplenial cortex was not changed by administration of PCP (25 mg/kg, i.p., 5 h), but that in the other layers of retrosplenial cortex was reduced by PCP. These results suggest that immediate early gene zif268 may, in part, play a role in the neurotoxicity of NMDA receptor antagonists such as PCP.

Animals↗

PubMed1999

Occurrence of dentate granule cell LTP without proximal dendritic Ca2+ increase.

We investigated activity-dependent calcium increases in proximal dendrites of dentate granule cells in the rat hippocampus, and its relationship with induction of LTP at perforant path synapses (PP-synapses). LTP was induced at PP-synapses by high-frequency stimulation (HFS; 100 Hz for 0.4 s), and the same HFS evoked a dendritic calcium increase in the proximal dendrite. However, bath-application of the L-type voltage-dependent calcium channel (VDCC) blocker nimodipine noticeably reduced this calcium increase without abolishing induction of LTP. This calcium increase mediated by high-threshold VDCCs is likely to be evoked by action potentials. LTP induction at PP-synapses is hence suggested to be independent of action potential-induced calcium increases in the proximal dendrite.

Animals↗

PubMed1999

Alteration in amino acids in motor neurons of the spinal cord in amyotrophic lateral sclerosis.

Little is known concerning the changes of amino acid composition in different regions of the spinal cord in patients with amyotrophic lateral sclerosis (ALS). We performed quantitative amino acid analyses in the posterior funiculus, the lateral corticospinal tract, and the anterior horn of cervical enlargement of the spinal cord from seven ALS patients, and the results were compared with those of seven patients with other neurologic diseases (control A) and seven patients without neurologic diseases (control B). The levels of collagen-associated amino acids, hydroxyproline, proline, glycine, and hydroxylysine, were markedly lower in the lateral corticospinal tract and the anterior horn of ALS patients than in controls A and B. The contents of the acidic amino acids glutamate and aspartate were also significantly decreased in the lateral corticospinal tract and the anterior horn of ALS patients as compared with those of controls A and B. These data suggest that decreased contents of collagen-associated amino acids and excitatory amino acids are related to the degeneration of the upper and lower motor neurons in the spinal cord in ALS.

Adult↗

PubMed1999

Diaminodiphenylsulfone resistance of Mycobacterium leprae due to mutations in the dihydropteroate synthase gene.

The nucleotide sequence analysis of the dihydropteroate synthase (DHPS) gene of six diaminodiphenylsulfone-resistant Mycobacterium leprae strains revealed that the mutation was limited at highly conserved amino acid residues 53 or 55. Though the mutation at amino acid residue 55 or its homologous site has been reported in other bacteria, the mutation at residue 53 is the first case in bacteria. This is the first paper which links the mutations in DHPS and sulfonamide resistance in M. leprae. This finding is medically and socially relevant, since leprosy is still a big problem in certain regions.

Dapsone↗

PubMed1999

Impairment of AMPA receptor function in cerebellar granule cells of ataxic mutant mouse stargazer.

The spontaneous recessive mutant mouse stargazer (stg) begins to show ataxia around postnatal day 14 and display a severe impairment in the acquisition of classical eyeblink conditioning in adulthood. These abnormalities have been attributed to the specific reduction in brain-derived neurotrophic factor (BDNF) and the subsequent defect in TrkB receptor signaling in cerebellar granule cells (GCs). In the stg mutant cerebellum, we found that EPSCs at mossy fiber (MF) to GC synapses are devoid of the fast component mediated by AMPA-type glutamate receptors despite the normal slow component mediated by NMDA receptors. The sensitivity of stg mutant GCs to exogenously applied AMPA was greatly reduced, whereas that to NMDA was unchanged. Glutamate release from MF terminals during synaptic transmission to GCs appeared normal. By contrast, AMPA receptor-mediated EPSCs were normal in CA1 pyramidal cells of the stg mutant hippocampus. Thus, postsynaptic AMPA receptor function was selectively impaired in stg mutant GCs, although the transcription of four AMPA receptor subunit genes in the stg GC was comparable to the wild-type GC. We also examined the cerebellum of BDNF knockout mice and found that their MF-GC synapses had a normal AMPA receptor-mediated EPSC component. Thus, the impaired AMPA receptor function in the stg mutant GC is not likely to result from the reduced BDNF-TrkB signaling. These results suggest that the defect in MF to GC synaptic transmission is a major factor that causes the cerebellar dysfunction in the stg mutant mouse.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Effects of azimilide, a KV(r) and KV(s) blocker, on canine ventricular arrhythmia models.

Using canine coronary artery ligation/reperfusion and adrenaline arrhythmia models, we determined the effects of azimilide, a class III antiarrhythmic agent, E-1-[[(5-(4-chlorophenyl)-2-furanyl) methylene]-amino]-3-[4-(4-methyl-1-piperazinyl)butyl]-2,4-imidazolidi nedione dihydrochloride. The coronary ligation/reperfusion arrhythmia experiments were divided into two groups, one using low heart rate halothane-anesthetized and the other using high heart rate pentobarbital-anesthetized dogs. Azimilide (6 mg kg(-1) + 0.1 mg kg(-1) min(-1) i.v.) prolonged the corrected QT interval (QTc), decreased the heart rate and suppressed the premature ventricular complexes during ligation (35 +/- 17 beats/30 min as compared with 909 +/- 246 in the control group), and also suppressed ventricular fibrillation induced by coronary ligation/reperfusion in the two groups (1/8 halothane-anesthetized dogs as compared with 7/8 dogs in the control group and 2/8 pentobarbital-anesthetized dogs as compared with 8/8 dogs in the control group). In adrenaline arrhythmia, azimilide hastened the onset of adrenaline arrhythmias and also aggravated the arrhythmias, showing proarrhythmic effects.

Anesthetics↗

PubMed1999

Differential effects of Bcl-2 overexpression on hippocampal CA1 neurons and dentate granule cells following hypoxic ischemia in adult mice.

In contrast to its known anti-apoptotic activity in sympathetic neurons, immortal neuronal cell lines, and primary cultured immature neurons of the central nervous system (CNS), the role of Bcl-2 in CNS neurons in the adult brain is poorly understood. In the present study, we examined effects of overexpression of Bcl-2 on selective neuronal death of the hippocampal CA1 neurons and the dentate granule cells induced by hypoxic ischemia in adult transgenic mice overexpressing human Bcl-2 under the control of neuron-specific enolase (NSE-hbcl-2). At the light microscopic level, numbers of TUNEL-positive cells with pyknotic nuclei were observed in the CA1 subfield of NSE-hbcl-2 transgenic mice, as well as that of wild-type mice, after hypoxic ischemic insult, although the onset of neuronal death was apparently delayed in NSE-hbcl-2 transgenic mice. The electron microscopic studies showed that morphological changes of the degenerating CA1 neurons from both groups were clearly distinct from ordinary apoptosis. In contrast, a significant amount of degenerating dentate granule cells from wild-type but not from transgenic mice had typical apoptotic nuclei by the treatment. The activation of caspase-3 was detected in the dentate granule cells but not that of the CA1 neurons. These results indicate that the overexpression of Bcl-2 effectively suppressed dentate granule cell apoptosis but only delayed cell death of the CA1 neurons induced by hypoxic ischemia, suggesting the occurrence of a non-apoptotic, caspase-3-independent mechanism for neuronal death in the CA1 subfield.

Animals↗

PubMed1999

Intracellular sodium accumulation during ischemia as the substrate for reperfusion injury.

To elucidate the role of intracellular Na+ kinetics during ischemia and reperfusion in postischemic contractile dysfunction, intracellular Na+ concentration ([Na+]i) was measured in isolated perfused rat hearts using 23Na nuclear magnetic resonance spectroscopy. The extension of the ischemic period from 9 minutes to 15, 21, and 27 minutes (at 37 degrees C) increased [Na+]i at the end of ischemia from 270.0+/-10.4% of preischemic level (mean+/-SE, n=5) to 348.4+/-12.0% (n=5), 491.0+/-34.0% (n=7), and 505.3+/-12.1% (n=5), respectively, whereas the recovery of developed pressure worsened with the prolongation of the ischemic period (95.1+/-4.2%, 84.3+/-1. 2%, 52.8+/-13.7%, and 16.9+/-6.4% of preischemic level). The kinetics of [Na+]i recovery during reperfusion was analyzed by the fitting of a monoexponential function. When the hearts were reperfused with low-[Ca]o (0.15 mmol/L) solution, the time constants of the recovery (tau) after 15-minute (8.07+/-0.85 minutes, n=5) and 21-minute ischemia (6.44+/-0.90, n=5) were significantly extended, with better functional recovery (98.5+/-1.4% for 15-minute [P<0.05]; 98.0+/-1.0% for 21-minute [P<0.05]) compared with standard reperfusion ([Ca]o=2.0 mmol/L, tau=3.58+/-0.28 minutes for 15-minute [P<0.0001]; tau=3.02+/-0.20 for 21-minute [P<0.0001]). A selective inhibitor of Na+/Ca2+ exchanger also decelerated the [Na+]i recovery, which suggests that the recovery reflects the Na+/Ca2+ exchange activity. In contrast, high-[Ca]o reperfusion (5 mmol/L) accelerated the [Na+]i recovery after 9-minute ischemia (tau=2.48+/-0.11 minute, n=5 [P<0.0001]) and 15-minute ischemia (tau=2.10+/-0.07, n=6 [P<0. 05]), but functional recovery deteriorated only in the hearts with 15-minute ischemia (29.8+/-9.4% [P<0.05]). [Na+]i recovery after 27-minute ischemia was incomplete and decelerated by low-[Ca]o reperfusion, with limited improvement of functional recovery (42. 5+/-7.9%, n=5 [P<0.05]). These results indicate that intracellular Na+ accumulation during ischemia is the substrate for reperfusion injury and that the [Na+]i kinetics during reperfusion, which is coupled with Ca2+ influx, also determines the degree of injury.

Animals↗

PubMed1999

Developmental regulation of action potential-induced Ca2+ entry in neocortical neurons.

Intracellular calcium plays a critical role in the regulation of membrane excitability, synaptic integration and synaptic plasticity. Using whole-cell recording and calcium imaging, we investigated intracellular calcium dynamics in apical dendrites of layer V pyramidal cells in the immature rat neocortex. Dendritic calcium increases induced by action potentials were only small on postnatal days 4-6 (P4-6), then underwent a gradual enhancement during the second post-natal week and were 2- to 3-fold larger on P16-18 than on P4-6. At P15-18 there were no significant differences in the calcium increases among the three subclasses of layer V pyramidal neurons: adapting regular spiking (RS), non-adapting RS and intrinsically bursting (IB) neurons. Developmental regulation of dendritic calcium dynamics may be crucial for functional maturation of the neocortex.

Action Potentials↗

PubMed1999

Postnatal development of action potential-induced dendritic calcium entry in neocortical layer II/III pyramidal cells.

By whole-cell patch-clamp recording and calcium imaging with fura-2, we investigated postnatal development of intracellular calcium dynamics in apical dendrites of layer II/III pyramidal cells in the rat visual cortex. Dendritic calcium increases, induced by single action potentials, occurred only slightly on postnatal days 8-10 (P8-10), and then underwent a gradual enhancement during the second postnatal week to become 2-3-fold larger on P16-18 than on P8-10. The results suggest that the developmental growth of calcium dynamics may play a critical role for functional development of neocortical neurons.

Action Potentials↗

PubMed1999

A predominant apoptotic death pathway of neuronal PC12 cells induced by activated microglia is displaced by a non-apoptotic death pathway following blockage of caspase-3-dependent cascade.

Activated microglia have been implicated in the regulation of neuronal cell death. However, the biochemical mechanism for neuronal death triggered by activated microglia is still unclear. When treated with activated microglia, neuronal PC12 cells undergo apoptosis accompanied by caspase-3-like protease activation and DNA fragmentation. Apoptotic bodies formed were subsequently phagocytosed by neighboring activated microglia. Pretreatment of the cells with the caspase-3-like protease inhibitor N-acetyl-Asp-Glu-Val-Asp-aldehyde did not reverse this cell death. Although Bcl-2 overexpression in the cells caused the inhibition of caspase-3-like protease activity and DNA fragmentation and the effective interference of apoptosis induced by deprivation of trophic factors, it could not suppress the activated microglia-induced neuronal death. At the electron microscopic level, degenerating cells with high levels of Bcl-2 were characterized by slightly condensed chromatins forming irregular-shaped masses, severely disintegrated perikarya, and marked vacuolation. Various protease inhibitors tested did not inhibit this cell death, whereas the radical oxygen species scavenger N-acetyl-L-cysteine significantly suppressed this death. Altogether, our study provides an alternative death pathway for the activated microglia-induced neuronal death by blockage of the caspase-3 protease cascade.

Acetylcysteine↗

PubMed1999

Partial nuclear localization of a bovine phosphoprotein, BCNT, that includes a region derived from a LINE repetitive sequence in Ruminantia.

BCNT, named after Bucentaur, is a protein that contains a 324-amino-acid region derived from part of a long interspersed DNA sequence element (LINE) in Ruminantia. However, the unique portion is completely missing in human and mouse BCNTs. Since no significant information on their function has been obtained by homology search, we at first examined cellular localization and biochemical characteristics of bovine BCNT to get a hint on its function. Subcellular fractionation and immunohistochemical analyses using a normal bovine epithelial cell line and bovine brain revealed that a significant amount of bovine BCNT is localized in the nuclei, while the major portion is present in the cytosol. Furthermore, it was shown that bovine BCNT is a phosphoprotein and that both bovine and human BCNTs are phosphorylated by casein kinase II in vitro. These results show that BCNTs consist of a unique family, probably a substrate of casein kinase II, which may contribute further to the understanding of gene evolution.

Amino Acid Sequence↗