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Biomedical subjects

K Sakurai

Publications and source records attributed to K Sakurai.

At least 109 records · Page 6Linked to original sources

Cooperative roles of colon and anorectum during spontaneous defecation in conscious dogs.

Colorectal motility during spontaneous defecation was investigated using force strain gauge transducers implanted in the proximal colon, distal colon, rectum, and anus in six dogs. One 24-hr recording and several defecation recordings were made in each dog. During 24-hr recordings, 29 giant contractions were observed in the distal colon. The giant contractions, which propagated to the rectum, accompanied evacuation more frequently than those that stopped at the distal colon (P < 0.05). Of 66 episodes of defecation, 63 (95%) were accompanied by a giant contraction of the distal colon. Of these, 57 (90%) propagated to the rectum. In three events, giant contraction originated at the rectum. The rectum relaxed prior to the contraction. The internal anal sphincter also relaxed. Migration of giant contraction to the rectum, rectal relaxation-contraction sequence and sphincter relaxation played important roles during defecation. Defecation is a consequence of successive phenomena occurring in both the colon and anorectum.

Anal Canal↗

Blockade of neuropsin, a serine protease, ameliorates kindling epilepsy.

The behavioural and electrographical abnormalities associated with seizures in epileptic (kindled) mice correspond with those of human epilepsy. In kindled mice, neuropsin was markedly increased in the hippocampus and cerebral cortices. A single intraventricular injection of monoclonal antibodies specific to neuropsin reduced or eliminated the epileptic pattern noted on electroencephalograms and, as a result markedly inhibited the progression of kindling. Therefore, neuropsin appears to be a key protein controlling pathogenic events in the hippocampus, and thus neuropsin inhibitors might be useful for treatment of epilepsy.

Animals↗

Transition of the craniocaudal velocity of the spinal cord: from cervical segment to lumbar enlargement.

RATIONALE AND OBJECTIVES: The authors investigate the craniocaudal velocity of the spinal cord over its full length by using magnetic resonance imaging. METHODS: A spin-echo pulse sequence with velocity encoding gradients was used to examine five normal volunteers. Oblique-axial phase images at nine levels, from cervical spinal cord to lumbar enlargement, were obtained with prospective electrocardiogram gating. Time-velocity curves were then generated for these levels. RESULTS: Every part of the spinal cord moves first caudally after the R-wave of the electrocardiogram, then cranially. When compared with the cranial levels, peak velocity tend to occur later and their values tend to be smaller at the more caudal levels. CONCLUSIONS: Craniocaudal velocity is transmitted from cervical segment to lumbar enlargement.

Adult↗

Detection of clonotypic changes of T cells after stimulation with Porphyromonas gingivalis.

The aim of this study was to investigate whether Porphyromonas gingivalis stimulation would induce a selective activation and expansion of a limited T-cell receptor V beta repertoire or T-cell clonotype. Using samples from patients with chronic inflammatory periodontal diseases, we examined TCRBV gene usage and T-cell clonotypes of peripheral blood mononuclear cells incubated in the presence or absence of P. gingivalis outer membrane through a combination of reverse transcription polymerase chain reaction (RT-PCR) and subsequent single strand conformation polymorphism (SSCP) analysis. There was no difference in the mean expression for most BV families with or without P. gingivalis outer membrane in the culture. However, in individual cases, a few BV gene families did become overexpressed or underexpressed following stimulation, although a consistent pattern did not emerge. SSCP analysis showed that several new distinct bands appeared after stimulation, indicating distinct clonal accumulations, although the number of distinct bands decreased in most cases. These data suggest that clonotypic change occurred following stimulation with P. gingivalis outer membrane. Furthermore, the possibility of superantigen stimulation by P. gingivalis is unlikely to be due to the small change in BV gene usage and clonal T-cell accumulations with P. gingivalis outer membrane stimulation, as evidenced by SSCP. Thus, RT-PCR and SSCP analysis is useful in evaluating the host response to periodontopathic antigens.

Antigens, Bacterial↗

Endovascular papillary angioendothelioma (Dabska tumor) in an elderly woman.

A patient with endovascular papillary angioendothelioma with a low grade of malignancy showing papillary proliferation of endothelioid cells is presented. The patient, an 83-year-old woman, underwent resection of a tumor of the neck. At operation a 9 x 7 cm cystic tumor containing yellow transparent liquid with clots was found in the subcutaneous tissue. Histological studies showed endothelioid cells with spindle-shaped nuclei proliferated in layers around the fibrovascular cores, which showed the characteristic appearance of papillary proliferation. These cells were immunohistochemically positive for CD31, CD34 and factor VIII-related antigen. Based on these observations, the tumor was considered to be an endovascular papillary angioendothelioma (Dabska tumor). Dabska tumor is a vascular tumor with a low grade of malignancy and usually occurs in infants and young children. About 13 cases of Dabska tumor have been reported. The occurrence of a Dabska tumor in an aged patient is considered to be rare.

Aged↗

Oxidative stress and cytotoxicity induced by ferric-nitrilotriacetate in HepG2 cells that express cytochrome P450 2E1.

Iron can potentiate the toxicity of ethanol. Ethanol increases the content of cytochrome P450 2E1 (CYP2E1), which generates reactive oxygen species, and transition metals such as iron are powerful catalysts of hydroxyl radical formation and lipid peroxidation. Experiments were carried out to attempt to link CYP2E1, iron, and oxidative stress as a potential mechanism by which iron increases ethanol toxicity. The addition of ferric-nitrilotriacetate (Fe-NTA) to a HepG2 cell line expressing CYP2E1 decreased cell viability, whereas little effect was observed in control cells not expressing CYP2E1. Toxicity in the CYP2E1-expressing cells was markedly enhanced after the depletion of glutathione. Lipid peroxidation was increased by Fe-NTA, especially in cell extracts and medium from the CYP2E1-expressing cells. Toxicity was completely prevented by vitamin E or by 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, which also decreased the lipid peroxidation. Levels of ATP were lowered by Fe-NTA, and this was associated with a decreased rate of oxygen consumption by permeabilized cells with substrates donating electrons to complexes I, II, and IV of the respiratory chain. This mitochondrial damage was prevented by vitamin E. Toxicity was accompanied by DNA fragmentation, and this fragmentation was prevented by antioxidants. Overexpression of bcl-2 decreased the toxicity and DNA fragmentation produced by the combination of CYP2E1 plus Fe-NTA, as did a peptide inhibitor of caspase 3. These results suggest that elevated generation of reactive oxygen species in HepG2 cells expressing CYP2E1 leads to lipid peroxidation in the presence of iron, and the ensuing prooxidative state damages mitochondria, releasing factors that activate caspase 3, leading to a loss in cell viability and DNA fragmentation.

Antioxidants↗

Improved nitric oxide detection using 2,3-diaminonaphthalene and its application to the evaluation of novel nitric oxide synthase inhibitors.

A specific and sensitive detection method for nitric oxide (NO) in living cells and tissue culture systems is required in the search for novel NO synthase (NOS) inhibitors. We have improved a fluorometric determination with 2,3-diaminonaphthalene (DAN) by the addition of 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl (PTIO) as an oxidant to form NO2 from NO. This method is 3 times more sensitive than that without PTIO, and is suitable for examining the NOS-inhibitory activity of large numbers of test compounds using a 96-well microplate reader. The improved method was applied to N-monomethyl-L-arginine (L-NMMA) as a known inhibitor and the derivatives of 2-phenyl-1,2-benzisoselenazol-3(2H)-one as teat compounds in order to investigate the effect of these compounds on NO production from activated rat aortic smooth muscle cells. The results obtained indicate that this method is suitable for the rapid assay of large numbers of test compounds.

2-Naphthylamine↗

Development of a fluorescent indicator for nitric oxide based on the fluorescein chromophore.

Endogenous nitric oxide (NO) appears to modulate many physiological and pathophysiological processes. In order to obtain direct evidence for NO functions in vivo, we have developed 4,5-diaminofluorescein (DAF-2) as a novel fluorescent indicator for NO. Green-fluorescent triazolofluorescein formed by the reaction of NO and DAF-2 affords high sensitivity for NO (detection limit: 5 nM). Membrane-permeable DAF-2 diacetate (DAF-2 DA) was loaded into activated rat aortic smooth muscle cells, where the ester bonds are hydrolyzed by intracellular esterase, generating DAF-2. The fluorescence in the cells increased in a NO concentration-dependent manner. This imaging method should be useful for studies of the dynamic biological actions of NO at the molecular level with fine temporal and spatial resolution.

Animals↗

Adrenal hemorrhage associated with Klebsiella oxytoca bacteremia.

Septic adrenal hemorrhage is classically caused by meningococcemia. An autopsied case is presented of a 45-year-old man with adrenal hemorrhage due to Klebsiella oxytoca bacteremia following placement of a central venous catheter. He died 5 hours after developing disseminated intravascular coagulation (DIC). The bacterial entry site may have been the catheter. The cause of death was considered to be pulmonary edema due to bacteremia rather than adrenal insufficiency due to hemorrhage. Septic adrenal hemorrhage should be recognized as a subtype of sepsis rather than adrenal insufficiency, and may be caused in conditions of severe sepsis with DIC, independent of the microorganic variety.

Adrenal Gland Diseases↗

Judgment of abnormal condylar surface forms in edentulous patients by temporomandibular joint noise.

Forty-five patients with upper and lower complete dentures with no subjective symptoms of temporomandibular disorder (TMD) were studied. On initial examination, the existence of abnormal condylar surface forms and temporomandibular joint (TMJ) noises were checked in order to study the relationship between these abnormalities. Zonography was conducted to observe the abnormal condylar surface forms, and stethoscopy was conducted to detect TMJ noises. The results demonstrated the relationship between the abnormal condylar surface forms and TMJ noise at the significant level of 0.02%. Furthermore, a judgment of the presence of the abnormal condylar surface form could be based upon the existence of TMJ noise at the sensitivity value of 0.60.

Aged↗

[Immunohistochemical study of p53, p27 and PCNA expression in esophageal cancer].

We evaluated the clinical significance of p53, p27 and PCNA expressions in esophageal squamous cell carcinomas. Operative specimens obtained from 70 patients with esophageal squamous cell carcinomas were investigated by staining with antibodies against p53, p27 and PCNA. The correlations among p53, p27 and PCNA expression, clinicopathologic factors and prognosis were studied. The expression of p53 was observed in 55.7%, and it did not correlate to histologic classification, growth pattern, and lymphatic invasion. The expression of p27 was observed in 48.6%, and it correlated to lymph node metastasis. The PCNA positive index (PCNA-PI) was high in the p27 negative cases. The p53 positive and p27 negative group revealed the worst survival rate among groups. Therefore, the p27 positive case, often associated with well differentiated carcinoma, tends to have a slower tumor-growth rate and better prognosis. It is suggested that immunohistochemical assessment on the p53 and p27 expressions would be useful to the recognize the malignant potential and differentiation of squamous cell carcinoma of the esophagus.

Aged↗

Protection by rebamipide against acetic acid-induced colitis in rats: relationship with its antioxidative activity.

The aim of this study was to examine the efficacy of rebamipide on acetic acid-induced colitis in rats. Colitis was induced in male Wistar/ST strain rats by intracolonic injection of 2 ml of 5% acetic acid. After 24 hr, lesion score, myeloperoxidase (MPO) activity, thiobarbituric acid-reactive substances (TBARS), and antioxidants were measured. Rebamipide was administered orally to the rats twice, once immediately and once 8 hr after the induction of the colitis at doses of 7.5, 15, and 30 mg/kg. To evaluate the pathogenesis of neutrophils in this colitis model, neutrophil-depleted rats were also investigated. Increases of TBARS and MPO activity and decreases of total glutathione, superoxide dismutase (SOD) activity, and alpha-tocopherol were observed in this model. Rebamipide at 30 mg/kg decreased the lesion score significantly, which was associated with the reduction of colonic TBARS. The decreases of total glutathione, SOD activity, and alpha-tocopherol were also inhibited significantly by rebamipide. The preventive effect of rebamipide in this colitis model may be attributed to its inhibition of reactive oxygen species production.

Acetic Acid↗

Extensive DNA damage induced by monochloramine in gastric cells.

Colonization of Helicobacter pylori (Hp) to gastric mucosa plays an important role for the pathogenesis of gastric mucosal lesions. We previously reported the importance of monochloramine (NH2Cl), which was derived from the interaction between Hp-urease and infiltrated leukocytes, in the course of Hp-associated gastric mucosal injury. While the long-term infection of Hp in the gastric mucosa is known to be one of the virulent factors which closely link to the gastric carcinogenesis, the details of its pathogenetic mechanisms remain speculative. The present study is designed to examine whether a NH2Cl could damage the DNA of gastric cells. Rabbit gastric mucosal cells (RGMC) or KATO III cells were cultured and suspended. Cell suspensions were exposed to HOCl, NH3 or NH2Cl for 15 min to give a final concentration of 0.1 mM. The magnitude of a double strand break of DNA was quantified by measuring the remnant double strand stained by ethidium bromide (EB), and the fluorescence intensity of EB was analyzed by spectrophotometer. Separately, cell nuclei were stained by fluorescent dye (Hoechst No. 33258) in order to evaluate the levels of chromatin condensation evoked by DNA fragmentation. The number of cells with chromatin condensation was counted. During the entire experimental period, more than 85% of cells were persistently viable in all groups. NH2Cl significantly induced the DNA double strand break as well as chromatin condensation in RGMC and KATO III cells (P < 0.05). However, NH3 or HOCl did not induce the DNA double strand break as well as chromatin condensation in both cells. NH2Cl, but not its precursors (NH3 or HOCl), enhanced the levels of DNA injury, suggesting the possible involvement in the carcinogenesis of Hp-associated gastric mucosa.

Ammonia↗

Differentiation of dys- and demyelination using diffusional anisotropy.

We attempted differential diagnosis of dysmyelination and demyelination in childhood using magnetic resonance diffusion weighted imaging. Pelizaeus-Merzbacher disease, one of the dysmyelination disorders, demonstrated diffuse high intensity of the cerebral white matter on T2-weighted images, which demonstrated diffusional anisotropy on diffusion weighted images. On the other hand, high intensity lesions on T2-weighted images in Krabbe disease, one of the demyelination disorders, lost diffusional anisotropy. Another demyelination disorder, Alexander disease-related disorder, also lost its diffusional anisotropy. In contrast to relatively high signal of the lesions on diffusion-weighted images in Krabbe disease (high signal type), the lesions in Alexander disease-related disorder showed low signal on diffusion-weighted images (low signal type). These results suggest that diffusion-weighted images will be clinically useful to differentiate dysmyelination from demyelination; both of them demonstrate similar high intensity lesions of the white matter on T2-weighted images.

Adult↗

Inhibition of experimental metastasis and cell adhesion of murine melanoma cells by chondroitin sulfate-derivatized lipid, a neoproteoglycan with anti-cell adhesion activity.

Chondroitin sulfate dipalmitoylphosphatidylethanolamine (CS-PE), when immobilized onto substratum, inhibited the adhesion of B16F10 mouse melanoma cells to fibronectin-coated dishes (anti-adhesion activity). CS-PE showed the most potent anti-adhesion activity for the melanoma cells among various GAG-PEs. CS-PE also inhibited the adhesion of B16F10 cells to Matrigel and the invasion of the cells into Matrigel. In the in vivo system of experimental metastasis, administration of B16F10 cells with CS-PE into C57BL/6 mice significantly inhibited lung metastasis. The inhibition degree of CS or hyaluronic acid-PE was lower than CS-PE. CS-PE administered intravenously into mice before the injection of B16F10 cells also inhibited metastasis. Pretreatment of B16F10 cells with CS-PE caused some but a lower degree of inhibition. When CS-PE was injected intravenously into mice, more binding in the lung was found than when CS was injected. CS-PE but not CS inhibited the retention in the lung of fluorochrome-labeled B16F10 cells when injected intravenously into mice. Since there was no significant effect of CS-PE on the viability and growth of B16F10 cells, the results suggest that CS-PE immobilized onto the subendothelial matrix may prevent melanoma cells from adhering to the subendothelial substrata of lung capillaries and inhibit subsequent invasion processes of metastasis.

Animals↗

Anti-inflammatory activity of superoxide dismutase conjugated with sodium hyaluronate.

Superoxide dismutase (SOD) from bovine erythrocytes was conjugated with sodium hyaluronate (HA) with a mean molecular weight of 10(6) to have greater anti-inflammatory activity in vivo. Amino groups of SOD were coupled with carboxyl groups in the hyaluronate molecule using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The HA-SOD conjugate was composed of 1.5 mol of SOD molecule per 1 mol of hyaluronate on the average, and retained 70% of the activity of unmodified SOD. The conjugate was essentially non-immunogenic in mice, and exhibited much higher anti-inflammatory activities than HA or SOD in models of inflammatory diseases such as ischemic oedema of the foot-pad in mice, carrageenin-induced pleurisy and adjuvant arthritis in rats.

Animals↗