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Biomedical subjects

K Okamoto

Publications and source records attributed to K Okamoto.

At least 91 records · Page 5Linked to original sources

Characterization of relaxed photo-excited magnetized states in prussian-blue analogous magnets.

Local structure of a photo- or x-ray-induced ferrimagnet Cs0.8Co1.3 [W(CN)8](3-cyanopyridine)1.9 x 2.1H2O was investigated by means of Co K- and W L-edge XAFS spectroscopy. The Co K-edge XANES spectra provide quantitative information on the ratio of Co(II) and Co(III) by virtue of the factor analysis. It was found that the Co(II) ratios are 81.9% at 300 K and 32.7% at 150 K. When the sample was irradiated by x rays at 30 K, a phase transformation occurred in a similar manner to the visible-light irradiation and a relaxed excited state that exhibits ferrimagnetism was formed. The relaxed excited state gives the Co(II) ratio of 67.0%. The W L(III)-edge EXAFS spectra determine the W-C, W-N and W-Co distances. The results of the distances were obtained as R(W-C)=2.16 A, R(W-N)=3.31 A, R(W-CoII)=5.37 A and R(W-CoIII)=5.19 A, irrespective of the three phases. The local structure of the relaxed excited state was found to be identical with that of the high-temperature (300 K) phase. The phase transformation is concluded to be caused by the charge transfer and the spin flipping from the -W(IV)(S=0)-CN-CoIII (S=0)- configuration to -W(V)(S=1/2)-CN-CoII (S=3/2)-.

Journal Article↗

Abeta amyloidosis induces the initial stage of tau accumulation in APP(Sw) mice.

To clarify how Abeta deposits induce secondary tauopathy, the presence of phosphorylated tau, glycogen synthase kinase 3alpha (GSK3alpha), GSK3beta, cyclin-dependent kinase 5 (CDK5), mitogen-activated protein kinase (MAPK) and fyn were examined in the Tg2576 brain showing substantial brain Abeta amyloidosis and behavioral abnormalities. Phosphorylated tau at Ser199, Thr231/Ser235, Ser396 and Ser413 accumulated in the dystrophic neurites of senile plaques. The major kinase for tau phosphorylation was GSK3beta. Smaller contributions of GSK3alpha, CDK5 and MAPK were suggested. Thus, brain Abeta amyloidosis has a potential role in the induction of tauopathy leading to the mental disturbances of Alzheimer's disease.

Alzheimer Disease↗

Epoprostenol sodium, a prostaglandin I2, lacks tumor promoting effects in a medium-term liver carcinogenesis bioassay in rats.

Potential modifying effects of epoprostenol sodium administration on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats daily received subcutaneously epoprostenol sodium at doses of 0, 1, 10 and 100 microg/kg, or were fed phenobarbital sodium (PB) at a dietary level of 500 parts per million (ppm) as positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. Prominent flushing of extremis and signs of behavioural depression occurred after injection and lasted for 1 h in rats given 100 microg/kg epoprostenol sodium. Such clinical signs were slight in rats treated with 10 microg/kg, but not observed with 1 microg/kg. Marked decrease in body weight gain was noted in rats given 100 microg/kg. Statistically significant changes in relative liver weights were not found in any group given the test chemical. Epoprostenol sodium did not significantly increase the quantitative values for glutathione S-transferase placental form (GST-P) positive liver cell foci observed after DEN initiation, in clear contrast to the positive control. The results thus demonstrate that epoprostenol sodium lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.

Animals↗

Inhibitory effect of nicergoline on superoxide generation by activated rat microglias measured using a simple chemiluminescence method.

We evaluated the effect of nicergoline on superoxide production by rat microglias using a 2-methyl-6-(p-methoxyphenyl)-3, 7-dihydroimidazo[1,2-a]pyrazin-3-one-dependent chemiluminescence assay. Nicergoline dose-dependently inhibited superoxide production by microglias stimulated with phorbol myristate acetate or opsonized zymosan, while it had no effect on superoxide production by a hypoxanthine-xanthine oxidase system. These results indicate that nicergoline does not have a scavenging effect, but has an inhibitory effect on superoxide generation by microglias. Although this drug is commonly used for treating chronic cerebral infarction, it may also have a protective effect on progression of Parkinson's disease or Alzheimer's disease.

Animals↗

Brain Abeta amyloidosis in APPsw mice induces accumulation of presenilin-1 and tau.

APPsw transgenic mice (Tg2576) overproducing mutant amyloid beta protein precursor (betaAPP) show substantial brain Abeta amyloidosis and behavioural abnormalities. To clarify the subsequent abnormalities, the disappearance of neurons and synapses and dystrophic neurite formation with accumulated proteins including hyperphosphorylated tau were examined. Tg2576 demonstrated substantial giant core plaques and diffuse plaques. The number of neurons was significantly decreased in the areas containing the amyloid cores compared with all other areas and corresponding areas in non-transgenic littermates in sections visualized by Nissl plus Congo red double staining (p<0.001). The presynaptic protein alpha-synuclein and postsynaptic protein drebrin were also absent in the amyloid cores. betaAPP and presenilin-1 were accumulated in dystrophic neurites in and around the core plaques. Tau phosphorylated at five independent sites was detected in the dystrophic neurites in the amyloid cores. Thus, the giant core plaques replaced normal brain tissues and were associated with subsequent pathological features such as dystrophic neurites and the appearance of hyperphosphorylated tau. These findings suggest a potential role for brain Abeta amyloidosis in the induction of secondary pathological steps leading to mental disturbance in Alzheimer's disease.

Alzheimer Disease↗

Sputum processing for evaluation of inflammatory mediators.

Neutrophil-dominated inflammation is prominent in the cystic fibrosis (CF) and chronic bronchitis (CB) airways. We assessed the degree of airway inflammation by measuring the sputum concentrations of interleukin (IL)-8, myeloperoxidase (MPO), and deoxyribonucleic acid (DNA). We determined the relationship among the concentrations of these mediators and investigated methodological problems that may be responsible for reported variability in measurements. Sputa obtained from 31 patients were solubilized with phosphate-buffered saline, dithiothreitol (DTT) (0.1% or 1%), or dornase alfa (0.2 mg/mL). The sputum concentration of IL-8 and MPO was measured by enzyme-linked immunosorbent assay (ELISA), and DNA was measured using microfluorimetry. There was a significant relationship among sputum IL-8, MPO, and DNA. For MPO (means +/- SD), CF was 1,392 +/- 771 vs. CB at 75 +/- 65 mcg/mL; P < 0.0001. For IL-8: CF was 239 +/- 154 vs. CB at 121 +/- 108 ng/mL; P = 0.0002. For DNA, CF was 1.707 +/- 1.25 vs. CB at 0.184 +/- 0.272 mg/mL; P < 0.0001. The MPO concentration in CF sputum was approximately double after in vitro treatment with dornase alfa (P < 0.0001). There is a greater concentration of IL-8, MPO, and DNA in CF than in CB sputa. There is a significant relationship among these inflammatory markers in sputum. DNA polymers bind myeloperoxidase in the sputum, and we speculate that treatment with dornase alfa may remove a source of MPO inhibition.

Adolescent↗

Pro- and anti-inflammatory cytokine gene expression in rat sciatic nerve chronic constriction injury model of neuropathic pain.

Cytokines may be pathophysiologically involved in hyperalgesia. Uncertainty exists about the types of cytokines and their site of action. To study the role of key pro- and anti-inflammatory cytokines in a chronic constriction model of neuropathic pain, mRNA expression of TNF, IL-1beta, IL-6, and IL-10 was quantified using competitive RT-PCR. Each cytokine mRNA in rat sciatic nerve was examined at days 3, 7, 14, and 45 after chronic constriction injury (CCI). We also undertook behavioral testing of these rats. Thermal warming and touch thresholds were significantly reduced at days 3, 7, and 14 in the CCI group, compared with the sham-operated group. Cytokine gene expression in sciatic nerve was significantly increased at day 7 for IL-1beta and IL-6 and at day 14 for TNF. Expression of IL-10 underwent a gradual and progressive increase, reaching statistical significance at day 45.

Animals↗

A study of risk factors for ovarian metastases in stage Ib-IIIb cervical carcinoma and analysis of ovarian function after a transposition.

OBJECTIVE: The objective of the present study was to examine the incidence and risk factors of ovarian metastases in cervical carcinoma. The function of transposed ovaries was also studied. METHODS: In order to analyze the risk factors of ovarian metastases, 255 slides of pathological specimens were reassessed by multivariate logistic regression analysis. Fifty-six patients were studied prospectively on the basis of the function of transposed ovaries. Basal body temperature and serum hormone levels were analyzed. RESULTS: Ovarian metastasis was identified in 2 of 485 (0.4%) patients with squamous cell carcinoma and in 12 of 146 (8.2%) patients with nonsquamous tumors of the cervix. Histologic type (P = 0.0014) and blood vessel invasion (P = 0.0433) were significant independent risk factors for ovarian metastases, as revealed by multivariate logistic regression analysis. Cumulative survival curves of preserved ovaries showed a significant (P < 0.005) decline in the group with postoperative radiotherapy. CONCLUSION: Preservation of ovarian function should be pursued in patients with squamous cell carcinoma of the cervix, provided that the patient has no other risk factor (blood vessel invasion) for ovarian metastases. Moreover, sufficient attention should be paid to the proper handling of ovarian blood vessels during surgery, in order to shield and protect them from exposure to scattered radiation administered during postoperative radiotherapy.

Adenocarcinoma↗

Analysis of the distribution of CAG repeats and X-chromosome inactivation status of HUMARA gene in healthy female subjects using improved fluorescence-based assay.

We investigated the polymorphic CAG-repeat distribution and the X-inactivation status of the human androgen receptor (HUMARA) gene in 58 female Japanese volunteers. Polymerase chain reaction amplification was performed using a fluorescent-dye-labeled primer under conditions specific for GC-rich targets, and fragments were analyzed. To estimate the length of these fragments, FAM-labeled (blue fluorescent) products were simultaneously compared with ROM-labeled size markers (red) that were created by sequencing various HUMARA fragments. The number of polymorphic CAG repeats of HUMARA in 116 alleles from 58 female subjects ranged from 15 to 28. Of the 58 volunteers, 51 (88.0%) were heterozygous. In 96% of the heterozygous female subjects, the allelic differences were no greater than 6 repeats. X-chromosome inactivation was calculated as the ratio of the area of the smaller peak to the sum of the areas of the smaller and larger peaks. The average ratio was 0.38 (range, 0.09-0.50). Preferential use of 1 allele, by more than 75% (ratio. <0.25). was observed in 5 volunteers (10.9%). The clonal nature of a patient with chronic myelogenous leukemia was easily identified. This method is sensitive enough to discriminate a difference of 1 triplet repeat.

Clonal Deletion↗

Myofascial flap without skin for intra-oral reconstruction. 1: Animal studies.

BACKGROUND: Although myofascial flaps are already used clinically in intra-oral reconstruction, the source and process of epithelialization remain unclear. METHODS: The process of epithelialization of grafted myofascia in the oral cavity was investigated using the latissimus dorsi muscle of Wistar strain rats. RESULTS: The use of myofascial tissue to fill in defects may maintain the space by preventing shrinkage and contracture of the wound, and this myofascial tissue may induce regeneration of the mucosal epithelium. Myofascia itself did not have the potential to epithelialize. Epithelialization progressed gradually along the surface of the granulated myofascia from the surrounding incised mucosal margin of the recipient site to the central portion. Immunohistochemical staining showed that keratinocyte growth factor-expressing cells were found mainly in the granulated myofascia. Within the study period, regenerated epithelium with orthokeratosis consisting of stratified squamous cells was thin and had scanty rete pegs, but it was similar to normal epithelium. CONCLUSION: Grafted myofascia in the oral cavity may play a space-making role, and induce regeneration of the mucosal epithelium, associated with the production of keratinocyte growth factor.

Animals↗

Myofascial flap without skin for intra-oral reconstruction. 2: Clinical studies.

BACKGROUND: Based on the results of our animal experiment, we evaluated the clinical usefulness of myofascial graft materials in the reconstruction of intra-oral soft-tissue defects. METHODS: An axial-pattern or random-pattern myofascial flap was grafted to reconstruct oral soft-tissue defects caused by tumor resection in ten patients. A pectoralis major myofascial flap was employed in four patients, and a platysma myofascial flap was employed in six patients. RESULTS: All flaps survived, and epithelialization progressed gradually from the surrounding incised mucosal margin. Cicatricial contracture of the wound seemed to be mild and the regenerated mucosa was more flexible than skin. Because the myofascial tissue had only raw surfaces, the handling of the flaps in the oral cavity was very flexible. Moreover, cosmetically unsatisfactory scar formation and dysfunction at the donor site were mild. CONCLUSION: We feel that the myofascial graft procedure is a very useful option for the reconstruction of intra-oral soft-tissue defects, and will soon become a common procedure. We refer to this procedure as the "biological-guided mucosa regeneration (BGMR)" technique.

Adult↗

Change in signal intensity on MRI of fat in the head of markedly emaciated patients.

The amount of fat in various parts of the body decreases in emaciated patients, but responds differently to disease processes. The order of disappearance of fat in various parts of the head has rarely been studied with MRI. We imaged ten patients with anorexia nervosa and one cachectic patient with a psychiatric disorder with a 1.5 T imager. Signal intensities of bone marrow of the skull, subcutaneous tissue, and orbits were assessed on T1- and T2-weighted images, and correlated with the body mass index (BMI) and haemoglobin concentration (Hb). On T1-weighted images, five patients (BMI 15.6-17.8 kg/m2, mean 16.6 kg/m2; Hb 10.1-14.2 g/dl, mean 13.8 g/dl) showed the normal pattern of fat. One (BMI 13.6 kg/m2, Hb 10.4 g/dl) lost the high signal of bone marrow, but high signal of subcutaneous tissue and the orbits was preserved. High signal from bone marrow and subcutaneous tissue disappeared in three patients (BMI 11.5-13.5 kg/m2, mean 12.5 kg/m2; Hb 7.9-9.7 g/dl, mean 8.7 g/dl), but orbital high signal was preserved. The remaining two patients (BMI 9.3 and 13.5 kg/m2, mean 11.5 kg/m2; Hb 7.6 and 8.9 g/dl, mean 8.3 g/dl) showed complete loss of high signal from fat in the head. The order of disappearance of fat (bone marrow, subcutaneous fat, then orbits) correlated with both BMI and Hb. Atrophy of bone marrow was demonstrated on T2-weighted images in five patients with BMI 13.5 kg/m2 or less, and Hb 9.7 g/dl or less.

Adipose Tissue↗

MRI in essential primary cutis verticis gyrata.

We report MRI findings in four patients with essential primary cutis verticis gyrata (CVG). The patients were all men, aged 49-81 years (mean 65 years). They had no symptoms related to this rare scalp condition, preceding scalp disease or associated systemic disease. Coronal images showed a characteristic corrugated appearance of the thickened scalp at the vertex, diagnostic of CVG. Neuroradiologists should be aware of this condition.

Aged↗

Is timing of death from tumor recurrence predictable after curative resection for gastric cancer?

It is still difficult to predict whether cancer in patients who undergo curative gastrectomy for gastric cancer will recur and when they will die of recurrence. This study clarified predictive factors related to timing of death from tumor recurrence. A multivariate analysis was used to assess the dependence of death on postoperative tumor recurrence and were the dependence of the timing of death on tumor recurrence. Patients were divided into two groups according to the timing of death: those who died of tumor recurrence less than 2 years after surgery and those who died more than 2 years after surgery. Depth of cancer invasion, regional lymph node metastasis, and tumor size were independently correlated with tumor recurrence after curative gastrectomy. Onlv the depth of cancer invasion independently correlated with the timing of death due to tumor recurrence. It might be possible to predict the timing of death from tumor recurrence by the depth of cancer invasion into the gastric wall.

Female↗

Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with obstructive jaundice.

We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative therapy for patients with unresectable malignant diseases involving the ductal confluence or the common hepatic duct. Fifteen patients with malignant biliary obstruction were treated by cholangiojejunostomy at our hospital. Two patients had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies were performed in 14 patients and segment V cholangiojejunostomy in 1. Contraindications for surgical resection were locoregional invasion of tumors involving the proper and/or common hepatic artery and portal vein in 15 patients and the presence of hepatic metastases in 6 patients. Liver metastases were detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative complications occurred in 2 patients (13%), but there was no leakage of the cholangioenteric anastomosis in our series. There was no operative mortality after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months after surgery, 7 showed a significant improvement in performance status (PS) (82 +/- 10%) 3 months after the surgery compared with the preoperative PS (70 +/- 7%). Four of the 9 patients had recurrent cholangitis as a late complication, but 4 were completely free from jaundice. Median survival after cholangioenteric bypass was 9 months (range, 2-25 months). With respect to tumor location, the median survival time was 4 months (range, 2-25 months) in patients with gallbladder carcinoma and 15.5 months (range, 12-22 months) in those with bile duct carcinoma. While the median survival period after surgery was only 3 months (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can provide useful palliation for malignant biliary obstruction when combined with careful patient selection.

Bile Duct Neoplasms↗

Pancreatic cancer complicated by disseminated intravascular coagulation associated with production of tissue factor.

A 54-year-old man was diagnosed as having pancreatic cancer and disseminated intravascular coagulation. His plasma tissue factor level on the 11th hospital day was 996 pg/ml (normal range, 120-270 pg/ml). He was treated with gabexate mesilate, antithrombin III, and low-molecular-weight heparin. However, he died of multiple organ failure on the 17th hospital day. The histological finding was poorly differentiated ductal adenocarcinoma of the pancreas, and the production of tissue factor in this lesion was revealed. Tissue factor is a factor that initiates blood coagulation; thus, its expression in pancreatic cancer is one of the causes of coagulation abnormalities in this disease. Although one report has demonstrated immunoreactivity for tissue factor in pancreatic cancer, the patient's detailed clinical course was not mentioned in that report. This is the first report to prove that pancreatic cancer produced tissue factor in a patient with disseminated intravascular coagulation.

Adenocarcinoma↗

Diagnostic value of serum markers of connective tissue turnover for predicting histological staging and grading in patients with chronic hepatitis C.

PURPOSE: Chronic hepatitis C is an insidiously progressive disease, in which repeated assessment of liver histology is required. Various serum fibrotic markers have now been introduced. Our present aim was to assess, by receiver operating characteristic analysis, the usefulness of serum fibrotic markers for diagnosing fibrotic staging and necroinflammatory grading in chronic hepatitis C. METHODS: Serum levels of procollagen type III N-terminal peptide (PIIINP), 7S fragment of type IV collagen (PIVNP), hyaluronan (HA), matrix metalloproteinase (MMP)-1, MMP-2, and tissue inhibitor of metalloproteinases (TIMP)-1 were measured in 169 patients with chronic hepatitis C. RESULTS: The accuracy of these tests for discriminating stages greater than F2 from stages less than F1 was superior to that for discriminating stage F3 from stages less than F2. The most useful test for predicting stages greater than F2 was the serum HA test (cutoff value, 50 ng/ml; sensitivity, 75%; specificity, 80%), and the next-most useful was the serum MMP-2 test (cutoff value, 550 ng/ml; sensitivity, 75%; specificity, 70%). The usefulness of these tests for discriminating moderate grade from grades less than mild was superior to that for discriminating grades more than mild from minimal grade. The most useful test for predicting moderate grade was the serum HA test (cutoff value, 60 ng/ml; sensitivity, 77%; specificity, 74%), and the second-most useful was the serum PIVNP test (cutoff value, 6.5 ng/ml: sensitivity, 74%; specificity, 75%). The combination of the most useful and next-most useful test results increased the accuracy of the diagnosis of staging and grading. CONCLUSIONS: These serum fibrotic markers, especially the serum HA test, would be clinically useful for assessing staging and grading in patients with chronic hepatitis C.

Adult↗