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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 19 recordsLinked to original sources

Microbleeds on gradient-echo T2(*)-weighted MR images from patients with multiple simultaneous intracerebral haemorrhages.

BACKGROUND: Multiple simultaneous intracerebral haemorrhages (ICH) occur rarely and the mechanism remains unknown. In this report, we compare several clinical factors of multiple haemorrhages, including microbleeds, with single intracerebral haemorrhages and discuss a potential explanation for their occurrence. METHODS: One hundred and ninety consecutive patients with intracerebral haemorrhage who were admitted within 24 hours after onset from January 2003 to November 2005 were included in the study. Several clinical factors, including the number of microbleeds on gradient-echo T2(*)-weighted magnetic resonance images, were compared between patients with single and multiple haemorrhages. FINDINGS: Computed tomography scans revealed that nine patients had multiple intracerebral haemorrhages. In all cases, five or more microbleeds were revealed on T2(*)-weighted magnetic resonance images. This was significantly higher than the number of microbleeds in patients with single intracerebral haemorrhage (p < 0.05). Systolic blood pressure on admission was > or =200 mmHg in seven of the nine patients and was higher than in patients with a single haemorrhage (p = 0.05). CONCLUSIONS: Elevated blood pressure induced by an initial haemorrhage was speculated to be the result of secondary haemorrhages in some patients with multiple microbleeds. Thus, strict blood pressure control may help to prevent the occurrence of multiple haemorrhages.

Adult↗

Purification, characterization, and potential applications of formate oxidase from Debaryomyces vanrijiae MH201.

Formate oxidase was found in cell-free extracts of Debaryomyces vanrijiae MH201, a soil isolate. After purification by column chromatography, the preparation showed a protein band corresponding to a molecular mass (MM) of 64 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The MM, estimated by a gel filtration, was 99 kDa. The preparation showed two and three bands on isoelectric focusing under denaturing and native conditions, respectively. These results suggest that the preparation contained three isoforms, each of which might be composed of alphaalpha, alphabeta, and betabeta subunits with apparently similar MM. The preparation acted on formate with K (m) and V (max) values of 11.7 mM and 262 micromol min(-1) mg(-1), respectively, at pH 4.5 and 25 degrees C, but showed no evidence of activity on the other compounds tested. The optimum pH and temperature were pH 4.0 and 35 degrees C, respectively. The preparation showed activities of 85% of the initial activity after storage at pH 6.0 and 4 degrees C for 8 weeks. When 10 mM formaldehyde was reacted with 2.0 U ml(-1) of the enzyme preparation at pH 5.5 and room temperature in the presence of 2.0 U ml(-1) of a microbial aldehyde oxidase and 100 U ml(-1) of catalase for 180 min, neither of formate nor formaldehyde was detected, suggesting that the reaction involved the quantitative conversion of formaldehyde to carbon dioxide.

Aldehyde Oxidase↗

The effect of dexamethasone on defective nephrin transport caused by ER stress: a potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases.

The mechanism by which glucocorticoids govern antiproteinuric effect in nephrotic syndrome remains unknown. Present study examined the protective role of dexamethasone (DEX) in the intracellular trafficking of nephrin under endoplasmic reticulum (ER) stress. Human embryonic kidney-293 cell line expressing a full-length human nephrin was cultured in mediums containing 5.5 or 25 mM glucose with or without DEX. The result revealed that glucose starvation evoked a rapid ER stress leading to formation of underglycosylated nephrin that was remained in the ER as a complex with calreticulin/calnexin. DEX rescued this interfered trafficking through binding to its receptor and stimulating the mitochondrial transcripts and adenosine 5' triphosphate (ATP) production, leading to synthesis of fully glycosylated nephrin. These results suggest that ER-stress in podocytes may cause alteration of nephrin N-glycosylation, which may be an underlying factor in the pathomechanism of the proteinuria in nephrotic syndrome. DEX may restore this imbalance by stimulating expression of mitochondrial genes, resulted in the production of ATP that is essential factor for proper folding machinery aided by the ER chaperones.

Adenosine Triphosphate↗

Decreased expression of NDRG1 is correlated with tumor progression and poor prognosis in patients with esophageal squamous cell carcinoma.

NDRG1 (N-myc downstream regulated gene-1) was reported to be necessary for p53-mediated apoptosis and to be regulated by PTEN (phosphatase and tensin homolog). In several cancers, it was suggested to be a tumor suppressor gene. Its significance in esophageal squamous cell carcinoma (ESCC) has not been studied. The objective of this study was to clarify the relation between clinicopathological and biologic factors in esophageal carcinoma and to determine the prognostic significance of the expression of NDRG1. Expression of NDRG1 mRNA was quantified by real-time reverse transcription polymerase chain reaction using a Lightcycler in 47 esophageal ESCC specimens. The data were analyzed with reference to clinicopathological factors. Among the esophageal cancer tissues, NDRG1 mRNA expression was significantly lower in tumors of more advanced pathological stage (0-I vs. II-IV; P = 0.0027) and local tumor invasion (T1-2 vs. T3-4; P = 0.0136). Patients who had low NDRG1 mRNA expression had a significantly shorter survival after surgery compared with patients who had high NDRG1 mRNA expression (log-rank test, P = 0.0478). Impaired NDRG1 expression may lead to more aggressive invasion of ESCC.

Aged↗

Pharmacology and toxicology of Bupleurum root-containing Kampo medicines in clinical use.

Kampo (Japanese traditional herbal) medicines have been produced by combining multiple crude drugs, almost all of plant origin but with some of animal or mineral origin, and contain a great many substances. Their effect is a combination of the various interactions of the constituent substances, whether they are enhancing, synergistic or suppressive. Kampo medicine has an overall effect that is different from the combined effects of individual crude drugs, and several side effects such as anorexia, slight fever and nausea have been reported in the treatment of certain disorders and disease states with Kampo medicines. Among 210 medical formulations used in Japan, some relevant information on the clinical uses, pharmacology and toxicology of six manufactured Kampo medical formulations, Shosaikoto, Daisaikoto, Saikokeishito, Hochuekkito, Saibokuto and Saireito, containing Bupleurum root are reviewed. Studies of some potential interactions between Kampo medicine and western drugs are also considered.

Animals↗

Application of in vivo cryotechnique to the examination of cells and tissues in living animal organs.

When all biological materials in cells and tissues of living animal organs are quickly and promptly frozen, immunolocalization of their components and structural features in situ is necessary to understand their in vivo functioning states. However, these direct morphological analyses were difficult to achieve by conventional chemical fixation methods during the last century. A new cryofixation method, named the "in vivo cryotechnique", in which the normal blood circulation in living animals is always retained at the moment of freezing, has become a powerful tool to visualize the real native morphology of cells and tissues with functional meaning. The "in vivo cryotechnique" can usually be combined with a wide range of subsequent preparation techniques, and can thereby enable us to perform various direct analyses on biological samples, reflecting the physiological functions of living animal organs.

Animals↗

Immunohistochemical study of serum albumin in normal and cadmium-treated mouse testis organs by "in vivo cryotechnique".

The in vivo injection of cadmium (Cd) was reported to induce blood-testis barrier disruption, and assumed to be an experimental model to examine junctional structures in seminiferous tubules. The purpose of this study is to investigate time-dependent changes of albumin permeability in the normal or Cd-treated mouse testis by our "in vivo cryotechnique" with immunohistochemistry, reflecting tight junctional (TJ) barriers of Sertoli cells. The albumin in the seminiferous tubules was firstly immobilized by the cryotechnique, in which normal blood circulation was always kept. The cryofixed testicular tissues were then processed for freeze-substitution, and embedded in the paraffin wax. Serial sections were immunostained by anti-mouse albumin antibody with peroxidase immunostaining, and also stained with hematoxylin-eosine (HE) for morphological observation. In normal seminiferous tubules, the immunoreaction products were localized around peritubular myoid cells and between Leydig cells, as well as in blood vessels. They were also localized as arch-like patterns around some spermatogonia in basal compartments of seminiferous tubules. Twenty-four and 48 hrs after Cd-treatment, some enlarged spaces and vesicular formations in the seminiferous epithelium were observed on the HE-stained sections. The albumin immunolocalization was detected not only in the basal compartments, but also in the adluminal compartments between Sertoli cells and germ cells. Thus, the structural disruptions of inter-Sertoli TJ barriers could be clearly demonstrated by the "in vivo cryotechnique".

Animals↗

Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer.

Constitutively activated signal transducers and activators of transcription (Stats), in particular Stat3 and Stat5, have been demonstrated to directly contribute to oncogenesis by stimulating cell proliferation and preventing apoptosis in various cancers. Stat3 is essential in mammary gland epithelial cell apoptosis and involution, whereas Stat5 is well established as a key factor in mammary epithelial cell growth and differentiation. Crosstalk between Stats and estrogen receptor (ER) has been demonstrated by several laboratories and we have focused on the role of Stat5 in ER-positive breast cancer. Using immunohistochemical techniques, we examined the expression of Stat3 and Stat5 in 517 human breast cancer tissues and analyzed their significance for prognosis and prediction of response to endocrine therapy. Stat5 expression was significantly correlated with histological grade (P<0.0001), ER (P=0.02), and progesterone receptor (P=0.026) expression. There was no difference between Stat3 expression and clinicopathological factors. In 346 patients with ER-positive breast cancer, patients with Stat5 positive tumors had significantly increased overall survival (P=0.0009) in multivariate analysis. There were 70 patients who received endocrine therapy as first-line treatment for metastatic breast cancer at relapse. The patients whose primary breast tumors were Stat5 positive, had significantly better response to endocrine therapy (P=0.04), and longer survival after relapse (P=0.0003), than those whose tumors were Stat5 negative. The present study demonstrates for the first time that Stat5 is a predictive factor for endocrine therapy response and a strong prognostic molecular marker in ER-positive breast cancer. Our data suggest that the expression of Stat5 is helpful in selecting patients who may benefit from endocrine therapy.

Adult↗

[Carcinomatous pericarditis successfully treated with thoracoscopic pericardial fenestration; report of a case].

We report a case of malignant pericardial effusion after lung cancer surgery treated with thoracoscopic pericardial fenestration. The patient was admitted to our hospital because of dyspnea. Computed tomography (CT) and ultrasound cardiography (UCG) revealed cardiac tamponade which was diagnosed as carcinomatous pericarditis by cytology. We attempted to inject 25 mg of cisplatin (CDDP) into the pericardial space twice. The response of the treatment was unexpectedly poor for the patient. The thoracoscopic pericardial fenestration was performed and the patient was discharged without a drainage tube on the 17th postoperative day. Malignant pericardial effusion is a common complication of advanced cancers and is often associated with significant morbidity. Thoracoscopic pericardial fenestration appears to be a safe, effective and minimally invasive treatment for patients with malignant pericardial effusion. This surgery might also have a favorable effect on the improvement of the quality of life for patients with malignant pericardial effusion resistant to chemotherapy.

Adenocarcinoma↗

Experimental observation of the 1/3 magnetization plateau in the diamond-chain compound Cu3(CO3)2(OH)2.

The magnetic susceptibility, high field magnetization, and specific heat measurements of Cu3(CO3)2(OH)2, which is a model substance for the frustrating diamond spin chain model, have been performed using single crystals. Two broad peaks are observed at around 20 and 5 K in both magnetic susceptibility and specific heat results. The magnetization curve has a clear plateau at one third of the saturation magnetization. The experimental results are examined in terms of theoretical expectations based on exact diagonalization and density matrix renormalization group methods. An origin of magnetic anisotropy is also discussed.

Journal Article↗

Glia maturation factor-beta is produced by thymoma and may promote intratumoral T-cell differentiation.

AIMS: To investigate whether Glia maturation factor-beta (GMFB) is expressed in thymomas and is associated with T-cell development. METHODS AND RESULTS: We investigated the expression of GMFB by immunohistochemistry in 86 cases of thymoma classified into five type A, 35 type AB, 11 type B1, 26 type B2, and nine type B3 thymomas according to the World Health Organization classification system. Immunoblotting and in situ hybridization (ISH) studies were also performed in selected cases. The results of the immunoblot analysis were in accordance with those of immunohistochemical scoring. The ISH study ascertained the tumour cells producing the protein. Immunohistochemically, GMFB expression was observed in one (20%) of type A, 32 (80%) of type AB, all (100%) of type B1 and B2, and eight (89%) of type B3 thymoma with statistically significant differences between type A and type AB, type B1, or type B2 thymoma, and between type B3 and type AB or type B2 thymoma. There was a significant correlation between GMFB expression and the amount of accompanying non-neoplastic T cells. GMFB promoted T-cell differentiation into CD4-/CD8+ cells when analysed by two-colour flow cytometry. CONCLUSIONS: The present study suggests that T-cell development in thymoma may be maintained partly by GMFB produced by the tumour cells.

Adult↗

Use of low dose dopamine, gabexate mesilate and ulinastatin reduces the water balance and pulmonary complication in thoracic esophagectomy patients.

SUMMARY: In spite of improvements in surgical technique and perioperative care, severe lung complication remains as the leading cause of morbidity in thoracic esophageal cancer patients who undergo esophagectomy. The purpose of this study was to evaluate the safety and effectiveness of postoperative drug therapy using low dose dopamine, gabexate mesilate, and ulinastatin on postoperative lung complication in esophageal cancer patients. Sixty-one patients operated for esophageal cancer from 1996 to 2000 were treated postoperatively with low dose dopamine (300 microg/kg/h), gabexate mesilate (80 mg/h), and ulinastatin (300 000 unit/day) as a study group. Seventy-four patients operated from 1987 to 1994 served as an historical control group. Various preoperative and perioperative medical parameters and water balance were analyzed. Postoperative pulmonary complications were observed in 26 patients (35.1%) in the control group and three patients (4.9%) in the study group, respectively (P < 0.0001). Preoperative and perioperative variables were not significantly different between the groups. Water balance from operation to postoperative day 3 in the study group was significantly lower than the control group. Postoperative use of low dose dopamine, gabexate mesilate, and ulinastatin significantly reduced pulmonary complications after esophagectomy. This may be partly attributable to negative water balance during the early postoperative days.

Carcinoma, Squamous Cell↗

Effect of paroxetine on marble-burying behavior in mice.

The present study was undertaken to investigate the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on marble-burying behavior in mice in comparison with those of fluvoxamine and clomipramine. Marble-burying test is extensively used as an animal model for obsessive/compulsive disorder. A significant inhibition in marble-burying behavior was observed with paroxetine, at a dose of 10 mg/kg. The earlier SSRI, fluvoxamine, also significantly inhibited marble-burying behavior at a dose of 30 mg/kg. Although clomipramine, a tricyclic antidepressant, caused an inhibition in marble-burying behavior, a high dose of 100 mg/kg was needed to show a significant effect. On the other hand, all the drugs used in the present study showed no significant changes in spontaneous locomotor activity at doses inhibiting marble-burying behavior. In conclusion, it was confirmed that paroxetine has a potent inhibitory effect on marble-burying behavior in mice, and could have a similar antiobsessive/anticompulsive activity in human beings.

Animals↗

[Metastatic carcinoma of the adrenal gland from large cell neuroendocrine carcinoma; report of a case].

A 69-year-old man had undertaken left upper lobectomy (ND 2 a) with partial resection of the left lower lobe under the diagnosis of a primary lung cancer, T2N0M0, stage IB in June, 2002. The histopathological diagnosis was large cell neuroendocrine carcinoma (LCNEC), T3N0M0, stage IIB. The patient was discharged on postoperative day 25. Abdominal computed tomography (CT) revealed an enhanced tumor in the left adrenal lesion, 3 cm in diameter, in October, 2003. Magnetic resonance imaging (MRI) showed a slightly low intensity mass on T1-weighted imaging and slightly high intensity on T2-weighted imaging without invasion to other organs. Tumor marker, NSE was slightly elevated on blood examination. Left adrenalectomy was performed with a surgical margin. Histopathologically, the tumor was diagnosed as metastasis of LCNEC. There is no evidence of recurrence for a year after surgery. Although a prognosis of LCNEC is poor in general, we should consider the resection of metastatic carcinoma of the adrenal gland from LCNEC for long-term survival expectantly.

Adrenal Gland Neoplasms↗

[Thymoma in elderly patients].

One hundred and twenty-three cases with primary thymoma have undergone an operation from 1972. Sixteen elderly patients (over 70 years old) were compared with 107 young patients in clinical appearance, pathological findings and outcome. There were no differences in Masaoka's classification, World Health Organization (WHO) pathological classification and frequency of complications as myasthenia gravis in both groups. In elderly patients different kinds of neoplasms often occurred during follow-up periods compared to in young patients. In both groups, basically policy of treatment is same. In the case of stage I or II, (extended) thymothymomectomy is performed. In the case of stage IIl, partial resection of invaded surrounding organs is added. We often perform preoperative corticosteroid therapy to shrink the tumor. In the case of stage IV a with pleural dissemination, thymothymomectomy with resection of all dissemination lesions is performed. The case with widespread invasion to pericardium and pericardial dissemination are considered as inoperable and undergo chemoradiotherapy. Postoperatively radiotherapy is added in the case of stage III and IV. In elderly patients 5 and 10 year survival rates were 60.2 and 48.1%. These were significantly worse compared to young patients. It depended on postoperative complications as sternomyelitis and different kinds of critical complications.

Age Factors↗

Angular distributions for (3,4)(Lambda)H bound states in the (3,4)He(e,e(')K+) reaction.

The (3,4)(Lambda)H and (4)(Lambda)H hypernuclear bound states have been observed for the first time in kaon electroproduction on (3,4)He targets. The production cross sections have been determined at Q(2)=0.35 GeV2 and W=1.91 GeV. For either hypernucleus the nuclear form factor is determined by comparing the angular distribution of the (3,4)He(e,e(')K+)(3,4)(Lambda)H processes to the elementary cross section 1H(e,e K+)Lambda on the free proton, measured during the same experiment.

Journal Article↗

Effects of anoxia on serum immunoglobulin and albumin leakage through blood-brain barrier in mouse cerebellum as revealed by cryotechniques.

The purpose of this study was to examine time-dependent topographical changes of leaking proteins from blood vessels in the mouse cerebellum to assess the effect of normal blood circulation on the blood-brain barrier (BBB). The distribution of leaking serum proteins was immunohistochemically examined by various cryotechniques including our "in vivo cryotechnique". The cryofixed cerebellar tissues were processed for the freeze-substitution method, and finally embedded in the common paraffin wax. Serial de-paraffinized sections were immunostained by anti-mouse immunoglobulin-G (IgG) or albumin antibody. By combination of the "in vivo cryotechnique", in which normal blood flow into the cerebellum was always kept in vivo, with the freeze-substitution method, serum IgG and albumin were clearly localized inside of cerebellar blood vessels. To examine abnormal leakage of blood vessels as a model of anoxia, some cerebellar tissues were partially removed from brains in the mouse skull and quickly frozen in the isopentane-propane within a minute. In such resected cerebellar tissues, serum IgG and albumin were diffusely immunostained in large areas around the blood capillaries, probably because of easy leakage of the serum components through the immediately changed BBB. To the contrary, no serum protein could be identified outside blood capillaries under living conditions of the anesthetized mice. The present combination method, both "in vivo cryotechnique" and freeze-substitution, for immunohistochemistry enabled us to examine the in vivo localization of serum components in mouse brains due to alteration of the BBB.

Animals↗

High-resolution record of Northern Hemisphere climate extending into the last interglacial period.

Two deep ice cores from central Greenland, drilled in the 1990s, have played a key role in climate reconstructions of the Northern Hemisphere, but the oldest sections of the cores were disturbed in chronology owing to ice folding near the bedrock. Here we present an undisturbed climate record from a North Greenland ice core, which extends back to 123,000 years before the present, within the last interglacial period. The oxygen isotopes in the ice imply that climate was stable during the last interglacial period, with temperatures 5 degrees C warmer than today. We find unexpectedly large temperature differences between our new record from northern Greenland and the undisturbed sections of the cores from central Greenland, suggesting that the extent of ice in the Northern Hemisphere modulated the latitudinal temperature gradients in Greenland. This record shows a slow decline in temperatures that marked the initiation of the last glacial period. Our record reveals a hitherto unrecognized warm period initiated by an abrupt climate warming about 115,000 years ago, before glacial conditions were fully developed. This event does not appear to have an immediate Antarctic counterpart, suggesting that the climate see-saw between the hemispheres (which dominated the last glacial period) was not operating at this time.

Journal Article↗