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Biomedical subjects

K Hatanaka

Publications and source records attributed to K Hatanaka.

At least 37 records · Page 2Linked to original sources

Development of rigor mortis is not affected by muscle volume.

There is a hypothesis suggesting that rigor mortis progresses more rapidly in small muscles than in large muscles. We measured rigor mortis as tension determined isometrically in rat musculus erector spinae that had been cut into muscle bundles of various volumes. The muscle volume did not influence either the progress or the resolution of rigor mortis, which contradicts the hypothesis. Differences in pre-rigor load on the muscles influenced the onset and resolution of rigor mortis in a few pairs of samples, but did not influence the time taken for rigor mortis to reach its full extent after death. Moreover, the progress of rigor mortis in this muscle was biphasic; this may reflect the early rigor of red muscle fibres and the late rigor of white muscle fibres.

Animals↗

Diagnosis of cyanide intoxication by measurement of cytochrome c oxidase activity.

Cytochrome c oxidase (CCO), a mitochondrial enzyme, is inactivated by cyanide or carbon monoxide (CO) intoxication. We measured CCO activity, in the major organs of the rat at various times after death caused by cyanide intoxication. Tissue samples were homogenized, and the CCO activity in the mitochondrial fraction was measured using ferrous cytochrome c as the substrate. The CCO activity inhibition was highest in the brain, although the cyanide concentration was lowest level. As a result of this and the clinical symptoms displayed, we consider the brain to be the primary organ of cyanide intoxication. As cyanide is highly toxic to humans, in small amounts and many patients and victims have already had some medical care, it is difficult to detect cyanide in criminal investigations. The CCO activities in various organs remained significantly low for 2 days after the cyanide intoxication, suggesting that the diagnosis may be possible by measuring not only the cyanide concentration but also the CCO activity.

Animals↗

Judging semantic and episodic incongruity: a magnetoencephalographic study.

Evoked magnetic fields over the entire head were measured during a semantic judgment task, in which conditions of the pre-test learning session were manipulated. Subjects learnt related and unrelated category-noun pairs, and were then asked to judge the relationship between category and noun. Unrelated pairs evoked activation around 400 ms in the left temporal area. In addition, newly presented related pairs, of which the categories were used to learn unrelated pairs, also evoked similar activities. Our findings suggest that these activities are not only related to the semantic incongruity between a pair of words as in previous studies, but also to the episodic incongruity between the learning and measurement sessions.

Adult↗

Role of phasic dynamism of p38 mitogen-activated protein kinase activation in ischemic preconditioning of the canine heart.

Although ischemic stress, including ischemic preconditioning (IP), activates p38 mitogen-activated protein kinase (MAPK), the relationship between p38 MAPK activation and the underlying cellular mechanisms of cardioprotection by IP is not verified in vivo. We examined the effects of the selective p38 MAPK inhibition on the cardioprotective effect of IP in the open-chest dogs. The coronary artery was occluded 4 times for 5 minutes, separated by 5 minutes of reperfusion (IP) followed by 90 minutes of occlusion and 6 hours of reperfusion. We infused SB203580 into the coronary artery during IP and 1 hour of reperfusion, during IP alone, and during sustained ischemia in the IP group. p38 MAPK activity markedly increased during IP but did not additionally increase at the onset of ischemia and was even attenuated at 15 minutes of sustained ischemia, and heat-shock protein (HSP) 27 was phosphorylated and translocated from cytosol to myofibril or nucleus without affecting total protein level at the onset of ischemia compared with the control group. SB203580 treatment (1 micromol/L) only during IP blunted the infarct size limitation by IP (37.3+/-6.3% versus 7.4+/-2.1% in the IP group, P:<0.01) and attenuated either phosphorylation or translocation of HSP27 during IP. Although the SB203580 treatment throughout the preischemic and postischemic periods had no significant effect on infarct size (33.3+/-9.4%) in this model, treatment with SB203580 only during ischemia partially mimicked the infarct size limitation by IP (26.8+/-3.5%). Thus, transient p38 MAPK activation during ischemic preconditioning mainly mediates the cardioprotection followed by HSP27 phosphorylation and translocation in vivo in the canine heart.

Animals↗

Neuromagnetic localization of N15, the initial cortical response to lip stimulus.

The initial cortical response of the trigeminal somatosensory evoked magnetic fields was measured for electrical stimulation of the lower lip in eleven subjects. The stimulus frequency was 0.7 Hz and stimulus intensity was nine times sensory threshold. The initial contralateral response was detected in 20 hemispheres at a latency of 14.6+/-1.3 ms and was named N15m. The equivalent current dipole of N15m was localized at the posterior bank of the central sulcus with anterior-superior orientation, and inferior to the dipole of N20m for median nerve stimulation.

Adult↗

Suppression of colorectal cancer growth using an adenovirus vector expressing an antisense K-ras RNA.

In human colorectal cancer, K-ras point mutations occur in approximately 40-50% of the cases, a frequency second only to pancreatic cancer (80-90%). Unlike pancreatic and lung cancers, however, the tumor-suppressive effect of antisense K-ras RNA expression has not been examined for colorectal cancers. A recombinant adenovirus vector expressing an antisense or sense K-ras gene fragment (AxCA-AS-K-ras or AxCA-S-K-ras) was first transduced into seven human colorectal cancer cell lines. Stable expression of antisense or sense K-ras RNA was detected by RNA blot analysis. Western blot analysis confirmed a reduction of up to 25% of K-ras-specific p21 protein in the antisense K-ras-transduced HCT-15 cells. In contrast to our previous findings on pancreatic cancer, the status of K-ras point mutations was not correlated with the growth-suppressive effect of the antisense K-ras vector: both the K-ras-mutation-positive and -negative colorectal cancer cell lines were suppressed for their growth in vitro. There was no growth-inhibitory effect on normal cells such as hepatocytes. Next, to test the efficacy in vivo, HCT-15 cells were inoculated subcutaneously into the left flank of SCID mice, and AxCA-AS-K-ras was injected intratumorally three times after the tumor mass was established. The infection of AxCA-AS-K-ras, but not the control AxCA-S-K-ras, significantly suppressed the growth of the HCT-15 subcutaneous tumor. This study shows that the adenovirus-mediated in vivo gene transfer of the antisense K-ras construct may be a useful therapeutic strategy for colorectal cancer.

Adenoviridae↗

Movement-related magnetic fields to tongue protrusion.

Movement-related magnetic fields (MRFs) associated with tongue protrusion were measured in five normal subjects using a helmet-shaped magnetoencephalography system. Bihemispherical two-dipolar patterns appeared from approximately -2000 or -1000 to 0 ms to the trigger signal indicating when protrusion of the tongue tip reached the frontal part of the palate. Equivalent current dipoles (ECDs) for the MRFs were localized on the central sulcus, 14.4 +/- 6.1 mm inferior (P < 0.0001) and 7.6 +/- 6.9 mm anterior (P < 0.01) to the ECD for the N20m in the somatosensory evoked fields for median nerve stimuli. The ECD orientations of MRFs were anterior and perpendicular to the central sulcus. These results correspond to the movement-related potentials for tongue protrusion previously recorded from subdural electrodes in patients with epilepsy. Magnetoencephalography can be applied to analyze cortical functions related to tongue movement with high resolution in time and space in normal subjects.

Adult↗

Somatosensory evoked fields in comatose survivors after severe traumatic brain injury.

OBJECTIVE: To evaluate the cortical function quantitatively in patients in the chronic phase of severe traumatic brain injury. METHODS: Thirteen patients with severe traumatic brain injury due to traffic accident followed by persistent consciousness disturbance and disability were studied. Somatosensory evoked magnetic fields (SEFs) for unilateral median nerve stimulation were measured using a whole-head magnetoencephalography system. The latency and electrical current dipole (ECD) moment for the N20m, P30m, N45m and P60m components were calculated and compared with those of 14 age-matched healthy adults. RESULTS: The peak latency of N20m was longer (P<0.05) and those of P30m and N45m were shorter (P<0.01) in the patients than in normal adults. The ECD moment of N20m and P30m was smaller and that of N45m and P60m was larger in the patients than in normal adults (P<0.01). CONCLUSIONS: These results can be explained by the hypothesis that diffuse brain injury induces decreased and delayed input of the somatosensory afferent and compensational amplification of the response in the primary somatosensory cortex. Middle-latency SEFs may be applicable as a cortical functional measure for patients with severe traumatic brain injury.

Adult↗

Successful non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) for Waldenström's macroglobulinemia with severe pancytopenia.

We report a 62-year-old male who underwent non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) because of his life-threatening severe pancytopenia due to refractory Waldenström's macroglobulinemia. This therapy was performed safely and he made a marked recovery from his cytopenia that had not been improved with any other therapy. Bone marrow aspirates showed post-transplant mixed chimerism during engraftment, and became completely donor-derived after a series of GVHD symptoms, without subsequent donor lymphocyte infusion. Our results suggest that non-myeloablative allogeneic PBSCT could be a good alternative for patients suffering from multi-drug resistant Waldenström's macroglobulinemia.

Critical Illness↗

Polyethylenimine-mediated gene transfer into pancreatic tumor dissemination in the murine peritoneal cavity.

Although peritoneal dissemination of cancer cells often occurs at the advanced stages of pancreatic, gastric or ovarian cancers, no effective therapy has been established. Cationic lipid-mediated gene transfer into peritoneal dissemination may offer a prospect of safe therapies, but vector improvements are needed with regard to the efficiency and specificity of the gene transfer. In this study, the intraperitoneal injection of plasmid DNA:polyethylenimine (PEI) complexes into mice was evaluated as a gene delivery system for the peritoneal disseminations. The luciferase and beta-galactosidase genes were used as marker genes. PEI was more efficient than the cationic lipids examined in this study in vivo, and the transgene was preferentially expressed in the tumors. Although PCR analysis showed that the injected DNA was delivered to various organs, the distributed DNA became undetectable by 6 months after the gene transfer. Blood chemistry and histological analysis showed no significant toxicity in the injected mice. This study demonstrated that the intraperitoneal injection of DNA:PEI is a promising delivery method to transduce a gene into disseminated cancer nodules in the peritoneal cavity.

Animals↗

Thiol-oxidizing agent diamide and acidic pH enhance lipid peroxidation of rat heart mitochondria and cardiolipin-cytochrome c complex.

In this study, we investigated lipid peroxidation in rat heart mitochondria hydrolyzed by phospholipase A2 (PLA2) and lipid peroxidation in a mitochondrial-mimetic lipid peroxidation system, where phospholipids such as cardiolipin (CL) and cytochrome c (Cyt c) were first mixed together and then PLA2 and calcium chloride were added to the mixture (CL-Cyt c-PLA2 system). Production of hydroperoxy and hydroxy compounds of linoleic acid (LA) in the mixture was measured by high performance liquid chromatography. The ratio of the total amount of hydroperoxy and hydroxy compounds of LA to that of LA was calculated as an index for lipid peroxidation (1000 x mol/mol). The index for lipid peroxidation in the rat heart mitochondria hydrolyzed by PLA2 at the physiological pH of 7.4 was 22.8 +/- 2.2 (mean +/- SD, n = 4) and that at the acidic pH of 6.7 was 41.8 +/- 2.0. In the presence of the thiol (SH)-oxidizing agent diamide, the index was 47.0 +/- 2.6 (pH 7.4). In the CL-Cyt c-PLA2 system, lipid peroxidation seemed to be due to three mechanisms: (1) oxidation of the LA (nonreleased form) constituent of CL by Cyt c (oxidation of CL by Cyt c); (2) oxidation of free LA, released from CL, involving the oxidation of CL by Cyt c (free LA oxidation by the CL-Cyt c complex); and (3) oxidation of free LA, released from CL, by Cyt c and calcium ions (LA-Cyt c-Ca system). The lipid peroxidation of the CL-Cyt c-PLA2 system was also enhanced by the addition of diamide and by an acidic pH of 6.7. The fact that the SH-oxidizing agent enhanced the lipid peroxidation in the CL-Cyt c-PLA2 system suggested that SH groups in the hemoprotein played an inhibitory role in lipid peroxidation in the system.

Animals↗

Primary lymphoma of spermatic cord.

Primary lymphomas of spermatic cord are extremely rare. In a review of the world medical literature, until now, only fourteen cases of spermatic cord lymphoma have been reported, and, furthermore, they have a poor prognosis even in patients with stage I disease. Herein, we report a new case of primary non-Hodgkin's lymphoma of the spermatic cord. In August, 1993, 76-year-old man visited an urological hospital with a compaint of a right intrascoral mass, and underwent orchiectomy. Macroscopically no invasive lesion in the testis was observed, and the tumorous lesion was restricted to the epididymis. The histopathological study indicated that he suffered from primary malignant lymphoma of the spermatic cord (B-cell, diffuse medium-sized cell type). As radiographic investigations showed no other invasive lesion, the patient was diagnosed to be in stage IE. He was followed only with clinical observation, and, in August, 1996, relapsed with extensive disease in the abdoninal cavity, and was transferred to our hospital. Fourty months after the orchiectomy, he died of progression of disease irrespective of the salvage radio-chemotherapies given to him.

Aged↗

Hand-assisted laparoscopic splenectomy for idiopathic thrombocytopenic purpura during pregnancy.

A successful case of a hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum for autoimmune thrombocytopenic purpura in a patient at 23 weeks' gestation is reported. Preoperative splenic arterial embolization was performed on the same day as the operation using painless contour embolic material and super-absorbent polymer microspheres. The abdominal wall retraction method first was applied to avoid the effects of pneumoperitoneum on systemic hemodynamic alterations. However, a sufficient surgical view could not be obtained, as the intra-abdominal organs were elevated because of the enlarged uterus. A surgical view with 4 to 6-mm Hg pneumoperitoneum was available for the hand-assisted splenectomy. The postoperative course was uneventful, and the patient vaginally delivered a healthy infant. A hand-assisted laparoscopic splenectomy with low-pressure pneumoperitoneum after splenic arterial embolization would be feasible for patients with autoimmune thrombocytopenic purpura during a relatively advanced pregnancy.

Adult↗

Transatrial repair of ventricular septal rupture under preoperative localization by transesophageal echocardiography.

We report about a 71-year-old woman with postinfarction ventricular septal rupture who was successfully treated by the transatrial closure under preoperative localization by transesophageal echocardiography. In an attempt at transatrial repair of the ventricular septal rupture, the most important thing is preoperative localization of the defect in the septum, which is located high and posterior, where it is smooth with relatively few trabeculations and can be readily exposed by retraction of the tricuspid valve.

Aged↗

Synthesis of oligosaccharide with controlled sequence.

A simple method for the synthesis of alternate heteropolysaccharide was investigated. Two types of modified glucose were combined into a cellobiose-type disaccharide monomer having only acetyl groups except a free hydroxyl group at C-3'. Polycondensation of this monomer, using stannic tetrachloride as catalyst, easily gave a novel copolysaccharide having regularly alternating 1,3-beta and 1,4-beta linkages.

Journal Article↗

FR167653, a cytokine synthesis inhibitor, exhibits anti-inflammatory effects early in rat carrageenin-induced pleurisy but no effect later.

We prepared a pharmacological profile of FR167653 (1-[7- (4-fluorophenyl)-1,2,3,4-tetrahydro-8-(4-pyridyl) pyrazolo[5,1-c][1,2,4]triazin-2-yl]-2-phenylethanedion sulfate monohydrate), a cytokine synthesis inhibitor, on early (5 h after irritation) and late (14-24 h after irritation) phases of rat carrageenin-induced pleurisy and on mediator-induced plasma exudation, in comparison with that of dexamethasone. In the early phase, FR167653 (30 mg/kg) and dexamethasone (0.3 mg/kg) equipotently suppressed plasma exudation and leukocyte infiltration. Furthermore, both agents significantly lowered the prostanoid levels in the exudate. Expression of cyclooxygenase-2 protein on leukocytes in the early phase of inflammation was not affected by dexamethasone, but it was suppressed by FR167653. However, FR167653 did not significantly affect the leukocyte mRNA level of cyclooxygenase-2. Both agents significantly suppressed the levels of both tumor necrosis factor-alpha and interleukin-1beta. FR167653 had a different pharmacological profile from dexamethasone in the late phase of this model in that, unlike dexamethasone, it did not affect cyclooxygenase-2 expression in mesothelial cells, the 6-keto-prostaglandin F1alpha level in the exudate or hyperplasia of mesothelium. Furthermore, unlike dexamethasone, FR167653 did not consistently inhibit mediator-induced plasma exudation. These results suggest that FR167653 or one of its analogs may be new candidates for therapy with a spectrum of activity distinct from that of current anti-inflammatory steroids.

Animals↗

Azido glycoside primer: a versatile building block for the biocombinatorial synthesis of glycosphingolipid analogues.

A lactoside primer, 12-azidododecyl beta-lactoside, was synthesized via the Koenigs-Knorr method by glycosylation of 1,12-dodecyldiol with perbenzoylated lactosyl bromide. The presence of the 2-O-acyl substituent in the donor gave the beta-lactoside, and an excess of acceptor ensured monoglycosylation of the diol. Mesylation of the omega-hydroxyl group in the aglycon, followed by displacement of the mesylate with azide and subsequent O-debenzoylation gave the desired omega-azidododecyl beta-lactoside. The azido glycoside primer was examined in mouse B16 melanoma cells for its feasibility as a building block for oligosaccharide biosynthesis. Uptake of the azido glycoside primer by B16 cells resulted in the sialylation of the galactose residue of the primer to give a glycosylated product having the same glycan as in ganglioside GM3. After 24 h incubation of B16 cells with the primers, the amount of sialylated omega-azidododecyl beta-lactoside primer was 75% of the amount of sialylated n-dodecyl beta-lactoside. However, after 48 h incubation, both primers gave equal amounts of the sialylated products. Interestingly, the remaining azido glycoside primer after 48 h incubation was 5.6-fold greater than that of the alkyl primer, indicating degradation of the alkyl primer to a larger extent than the omega-azido glycoside primer. The facile chemical synthesis and the efficient uptake in cells make the azido glycoside primer a versatile building block for the biocombinatorial synthesis of glycolipid oligosaccharides.

Animals↗

Are the anti-inflammatory effects of dexamethasone responsible for inhibition of the induction of enzymes involved in prostanoid formation in rat carrageenin-induced pleurisy?

Since anti-inflammatory steroids modulate multiple gene expression, including the expression of prostaglandin H synthase-2 and phospholipase A(2), at the molecular level, we studied the effects of dexamethasone on rat carrageenin-induced pleurisy to elucidate whether regulation of phospholipase A(2) and prostaglandin H synthase-2 expression is the primary mechanism of its anti-inflammatory action. Suppression of plasma exudation by a lower dose of dexamethasone (0.3 mg/kg) was almost equal to that by aspirin (100 mg/kg), but that by higher dexamethasone doses (3 and 30 mg/kg) was considerably stronger, suggesting the involvement of effects other than that on prostanoid formation. The lower dose of dexamethasone also significantly reduced the pleural exudate neutrophil count and prostanoid levels. However, this dose affected neither the prostaglandin H synthase-2 level nor the phospholipase A(2) activity in the exudate cells. The prostaglandin H synthase-2 level was affected only at the higher doses, while phospholipase A(2) activity was not. These results suggest that the anti-inflammatory effects of dexamethasone in acute inflammation cannot be ascribed to direct interference with prostanoid formation via suppression of phospholipase A(2) and prostaglandin H synthase-2 expression.

Animals↗