[Ca and Na regulation in cardiac cells].
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Calcium↗
Biomedical subjects
K Hashimoto
Publications and source records attributed to K Hashimoto.
[Future antihypertensive drugs].
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Animals↗
[A case report of successful transcatheter arterial embolization therapy for osseous metastasis of hepatocellular carcinoma].
A 74-year-old man was admitted to our hospital with a chief complaint of severe local pain of the hip joint. Radiological findings showed a metastasized lesion on the left side of the pelvic wall originated from hepatocellular carcinoma (HCC) in the anterior segment of the liver. Transcatheter arterial embolization (TAE) therapy using epirubicin, Lipiodol and Spongel was successfully performed twice for primary HCC, and four times for osseous metastasis of HCC. After TAE therapy, the size of the metastasized lesion decreased with relief of pain, and an improvement in performance status of 4 to 2 was achieved. In conclusion, TAE therapy is thought to be very useful in the treatment of osseous metastasis of HCC with severe local pain.
Aged↗
[Intrapericardiac instillation of epirubicin for carcinomatous cardiac tamponade from breast cancer].
Three cases of carcinomatous cardiac tamponade from breast cancer are presented. All patients have had another recurrence and history of treatment. Though the prognoses were considered to be unfavorable, pericardiac drainage and the instillation of epirubicin were effective. Side effects of fever and dyspnea were experienced temporarily by two patients with no serious events. Following the systemic chemotherapy, two patients needed no supplemental drainage. All patients had a sufficient quality of life for about 1 year or longer. We found that positive therapy can be significant for such patients with advanced disease.
Aged↗
[Effectiveness of docetaxel plus cisplatin in large cell lung cancer showing little response to prior chemotherapy with MVP].
The present patient was a 53-year-old male who had large cell lung cancer of c-T4N1M0. We administered multi-drug regimen including mitomycin C, vindesine and cisplatin (CDDP) because of cancer invasion into the great vessels seen on a chest CT. After 3 courses, the cancer showed no change in size. Therefore, we adopted chemotherapy of docetaxel (Taxotere: TXT) and CDDP. After 4 courses, the size of the mass had decreased (partial response). The only major toxic defect was grade 3 neutropenia. A good response to TXT and CDDP could lead to complete resection of lung cancer. It is suggested that TXT is effective in the treatment of large cell lung cancer.
Antineoplastic Combined Chemotherapy Protocols↗
[Combined use of ante- and retrograde cardioplegia: limited efficacy in elective coronary artery bypass].
One Hundred and twenty-four patients undergoing elective coronary bypass surgery were retrospectively selected and divided into two groups according to their difference of cardioplegic methods, either antegrade (AC) only (n = 65) or combination of ante- and retrograde (AC + RC) cardioplegic delivery (n = 64). Myocardial blood flow in the right (RV) and left ventricles (LV) was measured during the cardioplegia by a laser Doppler. Peak CPK-MB levels were compared postoperatively between the two groups and more in detail according to extent of coronary obstructive disease. 1) The antegrade administration of cardioplegic solution provided preferential flow to the RV compared to the LV, whereas the retrograde administration resulted in the opposite result (AC; LV 6.9 +/- 4.7, RV: 8.6 +/- 5.3, p < 0.05, RC; LV: 9.0 +/- 4.9, RV: 5.9 +/- 4.6 ml/min/100 g, p < 0.05). This result suggested that the combination of both administrations was meaningful to obtain uniform distribution of cardioplegic solution. 2) The peak CPK-MB, compared in the entire two groups, was slightly low in the combination use (AC; 48 +/- 16, AC + RC; 43 +/- 15 IU/l, p = 0.08), but the clinical meaning did not exist. However, in the severe cases, which involved two of following criteria (left main disease, severe occlusion of left or right coronary), the max CPK-MB level was statistically decreased by the combined use of ante- and retrograde cardioplegia (AC; 50 +/- 16, AC + RC; 40 +/- 12 IU/l, p < 0.05). We concluded that the merit of combined use was limited to the cases with severely extended coronary obstructive disease.
Aged↗
[A clinical case of 13 years old boy of aspirin-induced asthma with food allergy].
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Adolescent↗
[The effect of sevoflurane and enflurane on renal sympathetic nerve activity in sinoaortic denerved rabbits].
We assessed the effects of sevoflurane and enflurane, i.e. halogenated volatile anesthetics, on blood pressure, heart rate, and renal sympathetic nerve activity (RSNA) in rabbits. To eliminate the influence of baroreceptor reflex, bilateral carotid sinus nerve branches and vagus nerves were resected before the measurements. Sevoflurane and enflurane [0.5-1.15 MAC (minimum alveolar anesthetic concentration)] did not significantly change heart rate, but decreased mean blood pressure in a concentration-dependent manner. On the other hand, while sevoflurane did not significantly attenuate RSNA, enflurane decreased it in a concentration-dependent manner. There was a significant difference between sevoflurane and enflurane in their effects on RSNA. These results suggest that a decrease in blood pressure caused by sevoflurane is related to factors other than sympathetic nerve activity, and that hypotension caused by enflurane is related more closely to attenuated activity of sympathetic nerve, at least, in comparison with sevoflurane.
Anesthetics, Inhalation↗
[A study of reduction of NF 2 protein, mRNA and loss of 22 q in sporadic meningiomas].
Neurofibromatosis 2(NF 2) is one of the tumor suppressor genes, and its disorder has been reported in sporadic meningiomas. We investigated some reduction of expression of NF 2 protein and mRNA in 33 sporadic meningiomas, using immunohistochemistry and in situ hybridization, respectively. Seventeen of 33 (51.5%) meningiomas demonstrated significantly reduced or absent NF 2 protein expression. Its mRNA was also reduced or absent in 11 of 24(45.8%) meningiomas, and some statistically significant correlation was shown between reductions of NF 2 protein and its mRNA. Furthermore, we studied about loss of 22 q in 5 meningiomas with fluorescence in situ hybridization. In the cases with reduction of NF 2 protein and/or mRNA, 22 q telomere signals were observed as loss of heterozygosity. On the other hand, in the cases with expression of NF 2 protein and mRNA, 22 q telomere signals were normal. In conclusion, reduction or absence of NF 2 protein and mRNA may play an important role in the tumorigenesis of about half number of sporadic meningiomas.
Chromosomes, Human, Pair 22↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗
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↗