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Biomedical subjects

K Okamoto

Publications and source records attributed to K Okamoto.

At least 199 records · Page 11Linked to original sources
PubMed2000

Lymphoepithelial cyst of the pancreas: report of a case.

An extremely rare case of a lymphoepithelial cyst (LEC) of the pancreas is described herein. A pancreatic cystic tumor was initially detected in a 50-year-old man at a medical checkup. On admission, his serum carbohydrate antigen (CA) 19-9 level was 8100 U/ml and a computed tomography scan revealed a well-circumscribed multilocular cystic tumor in the pancreatic head and body. Magnetic resonance cholangiopancreatography showed no communication between the pancreatic ducts and the tumor. A distal pancreatectomy with lymph node dissection was performed because the lesion was suspected to be a mucinous cystadenoma or cystadenocarcinoma of the pancreas. However, histological examination revealed that the cyst was lined by stratified squamous epithelium and surrounded by lymphoid tissue. thereby confirming the diagnosis of LEC of the pancreas. The superficial layer of squamous epithelium and the cystic contents were found to be immunohistologically positive for CA19-9. Establishing a preoperative diagnosis of LEC is quite difficult because it resembles other cystic neoplasms of the pancreas in radiographic features and is frequently associated with an elevation of serum tumor markers such as CA19-9.

Biomarkers, Tumor↗
PubMed2000

Long-term benefit of extended lymphadenectomy with gastrectomy in distally located early gastric carcinoma.

BACKGROUND: Extended lymphadenectomy performed with gastrectomy has been reported to prolong survival of patients with early gastric cancer. However, some authors question the value of extensive lymphadenectomy in these patients, especially since much recent discussion of patient quality of life after gastrectomy has favored less invasive operations. METHODS: We retrospectively analyzed 485 patients who had undergone gastrectomy for early cancer in order to evaluate the effect of extended versus limited lymphadenectomy on postoperative survival. Various prognostic factors were examined for patients whose tumors were located in the distal third of the stomach. RESULTS: Although extended radical lymphadenectomy did not prolong postoperative survival when early gastric cancer was located in the middle or proximal third of the stomach, it did when the tumor occupied the distal third. CONCLUSIONS: Performance of extended radical lymphadenectomy was a significant prognostic factor for early gastric cancer patients when tumors were located in the distal third of the stomach.

Female↗
PubMed2000

Uncoupling effect of anacardic acids from cashew nut shell oil on oxidative phosphorylation of rat liver mitochondria.

Anacardic acids are one of natural products found in not only the cashew nut shell oil but also the nut and fruit juice. The present study was conducted to investigate the uncoupling effect of anacardic acids on oxidative phosphorylation of rat liver mitochondria using succinate (plus rotenone) as a substrate. Four anacardic acids with C15:0, C15:1, C15:2 or C15:3 as an alkyl side chain exhibited uncoupling effects similar to the classical uncoupler, 2,4-dinitrophenol on ADP/O ratio, state 4 and respiratory control ratio (RCR). Anacardic acid with C15:1 side chain was most effective for uncoupling of these compounds. Salicylic acid, which has no alkyl side chain, exhibited a very weak uncoupling effect on oxidative phosphorylation. When the carboxyl group in anacardic acids was lost converting them to the corresponding cardanols, uncoupling activity dramatically decreased regardless of the number of double bonds in the long alkyl chain. These results suggest that the C15 alkyl side chain as well as the carboxyl group may play an important role in assisting the uncoupling activity of anacardic acids in liver mitochondria of animals. This study provides the first evidence of an uncoupling effect of anacardic acids on liver mitochondria

2,4-Dinitrophenol↗
PubMed2000

Diverse mechanisms of osteoblast spreading on hydroxyapatite and titanium.

Hydroxyapatite (HA) is an osteoconductive implant material. We previously demonstrated that RGD peptides regulate the spreading of HOS cells on HA but not on titanium, speculating that the osteoconductivity of HA might be attributed to this RGD domain-dependent spreading of osteoblasts. To confirm this hypothesis, the molecules which regulate the spreading of HOS cells on HA and on titanium were investigated. The 50% effective dose (ED50) of RGD peptide for the spreading on HA was five fold lower comparing to titanium. Anti-alphaV integrin antibody, vitronectin, and fibronectin inhibited the spreading on HA but not on titanium. In Western blot analysis, vitronectin and fibronectin were found in components adsorbed to HA but not to titanium. Taken together, the spreading of HOS cells on HA but not on titanium requires the interaction of alphaV integrin and its ligands. The ED50 of the RGD peptides on titanium but not on HA was remarkably reduced by neuraminidase treatment, that by itself could not inhibit the spreading on both materials. This phenomenon suggests that RGD domain and sialic acid cooperatively but not independently mediate the spreading of HOS cells on titanium. Collectively, the molecules regulating the spreading on HA are apparently different from those on titanium. The spreading of osteoblasts mediated by RGD domain of vitronectin and fibronectin might contribute to the osteoconductive ability of HA.

Biocompatible Materials↗
PubMed2000

M-S vibrational study in three-coordinate thiolato compounds (NEt4)2[M(SC6H4-p-X)3] and (NEt4).

By using p-substituted benzenethiolate ligands, the novel three-coordinate copper(I) and silver(I) thiolato complexes (NEt4)2[Cu(SC6H4-p-X)3] (X=Cl (1) and Br (2)), (NEt4)2[Ag(SC6H4-p-X)3] (X=Cl (3) and Br (4)) and novel clusters (NEt4)2[M4(mu-SC6H4-p-Cl)6] (M=Cu (5) and Ag(6)) have been prepared and structurally characterized by single crystal X-ray diffraction. All the complexes have three-coordinate sites having point-group D3h symmetry. The three-coordinate mononuclear silver(I) complexes 3 and 4 are the first examples. The M-S stretching bands were determined by far-IR and FT-Raman spectroscopies; nu(Cu-S) 363-372 cm(-1) and nu(Ag-S) 353-363 cm(-1). These results indicate that M-S stretching vibration energy in the three-coordinate metal(I) site of the mononuclear compounds or clusters is around 340-380 cm(-1), and it is a useful tool for determining their coordination modes.

Benzene Derivatives↗
PubMed2000

The role of the [2Fe-2s] cluster centers in xanthine oxidoreductase.

Xanthine oxidoreductases (XOR), xanthine dehydrogenase (XDH, EC1.1.1.204) and xanthine oxidase (XO, EC1.2.3.2), are the best-studied molybdenum-containing iron-sulfur flavoproteins. The mammalian enzymes exist originally as the dehydrogenase form (XDH) but can be converted to the oxidase form (XO) either reversibly by oxidation of sulfhydryl residues of the protein molecule or irreversibly by proteolysis. The active form of the enzyme is a homodimer of molecular mass 290 kDa. Each subunit contains one molybdopterin group, two non-identical [2Fe-2S] centers, and one flavin adenine dinucleotide (FAD) cofactor. This review focuses mainly on the role of the two iron-sulfur centers in catalysis, as recently elucidated by means of X-ray crystal structure and site-directed mutagenesis studies. The arrangements of cofactors indicate that the two iron-sulfur centers provide an electron transfer pathway from molybdenum to FAD. However, kinetic and thermodynamic studies suggest that these two iron-sulfur centers have roles not only in the pathway of electron flow, but also as an electron sink to provide electrons to the FAD center so that the reactivity of FAD with the electron acceptor substrate might be thermodynamically controlled by way of one-electron-reduced or fully reduced state.

Amino Acid Sequence↗
PubMed2000

Development of an industrially stable process for L-threonine fermentation by an L-methionine-auxotrophic mutant of Escherichia coli.

Escherichia coli KY10935, an L-methionine-auxotrophic mutant, has the ability to produce 100 g/l of L-threonine under limited conditions of DL-methionine, but occasionally exhibits overgrowth with a concomitant decrease in L-threonine production. We found that the growth of the producer depended not only on the availability of DL-methionine but also on that of iron, and that the dependence on iron caused abnormal fermentations in response to fluctuations in the iron concentration among lots of corn steep liquor, a cheap natural material used as the production medium. To overcome this problem, culture conditions were re-optimized with respect to the amounts of both dl-methionine and iron added in the medium so that the growth was controlled irrespective of the lot of corn steep liquor, to establish a stable industrial process with high productivity.

Journal Article↗
PubMed2000

Histaminergic effect on apoptosis of rat small intestinal mucosa after ischemia-reperfusion.

This study aimed to examine the relationship between a harmful effect of histamine and apoptosis following ischemia-reperfusion in the rat intestine. The superior mesenteric artery was occluded for 60 min followed by reperfusion for 60 min. Rats were infused with H1-receptor antagonist (chlorpheniramine maleate) or H2-receptor antagonist (cimetidine). Additional rats were pretreated with aminoguanidine (100 mg/kg). Percent apoptosis in the intestinal mucosa increased after reperfusion, but neither H1 nor H2 antagonists had any effect on apoptosis. Aminoguanidine pretreatment inhibited activity of diamine oxidase and increased the plasma histamine concentration. Aminoguanidine attenuated the increase in mucosal apoptosis following reperfusion. Apoptosis induced by an ischemic insult to the intestinal mucosa was not related to an undesirable effect of histamine. Attenuation of increased intestinal apoptosis might be due to increased plasma histamine level and/or other pharmacological action of aminoguanidine, including inhibition of inducible nitric oxide synthase.

Animals↗
PubMed2000

FK506 augments glucocorticoid-mediated cyclooxygenase-2 down-regulation in human rheumatoid synovial fibroblasts.

Prostaglandins (PG) formed by cyclooxygenase (COX) enzymes are important mediators of inflammation in rheumatoid arthritis. The contribution of the inducible COX-2 to inflammation in the rheumatoid synovium is well documented. We examined the regulation of COX-2 mRNA and protein expression in response to both glucocorticoids (GC) and FK506 using rheumatoid synovial fibroblasts. Combined treatment of FK506 and a low concentration of dexamethasone (DEX) (10(-9) M) down-regulated synovial COX-2 mRNA and protein expression. In contrast, neither FK506 nor DEX (10(-9) M) alone influenced COX-2 expression. Immunocytochemical studies showed that pretreatment with FK506 enhanced the nuclear translocation of the glucocorticoid receptor (GR) in synovial fibroblasts in the presence of low concentrations of DEX (10(-9) M). Transient transfection experiments showed that treatment of cells with FK506 enhanced the expression of glucocorticoid-responsive gene reporter in the presence of DEX (10(-9) M). NF-kappaB is known to mediate the transcriptional activation of the COX-2 gene. Electrophoretic mobility shift assay demonstrated that DNA-binding activity of NF-KB was suppressed more profoundly by FK506 plus DEX (10(-9) M) treatment with those of DEX (10(-9)M) alone in IL-1beta-stimulated synovial cells. Our results indicated that FK506-induced potentiation of GR-mediated repression of synovial COX-2 gene transcription is the result of increased translocation of GR to the nucleus and subsequent repression of NF-kappaB transactivation. Our results also suggest that FK506 may exert anti-inflammatory effects in the rheumatoid synovium by potentiating GR-mediated signal transduction.

Arthritis, Rheumatoid↗
PubMed2000

Novel gene therapy for rheumatoid arthritis by FADD gene transfer: induction of apoptosis of rheumatoid synoviocytes but not chondrocytes.

Synovial cells in the rheumatoid synovium show abnormal proliferation, leading to joint destruction. Rheumatoid synovial cells express functional Fas antigen and are susceptible to Fas-mediated apoptosis. We have proposed the induction of apoptosis by Fas/Fas ligand system of proliferative rheumatoid synovium as a novel therapy for rheumatoid arthritis (RA). We have recently reported that Fas-associated death domain protein (FADD) plays a key role in Fas-mediated apoptosis of synovial cells in patients with RA. In this study, we determined whether FADD gene transfer could induce apoptosis of RA synoviocytes in vitro and in vivo. Transfection of FADD gene by adenoviral vector into cultured RA synoviocytes induced up-regulation of FADD expression and apoptosis. In addition, local injection of FADD adenovirus (Ad-FADD) eliminated synoviocytes in vivo by induction of apoptosis of proliferating human rheumatoid synovium engrafted in severe combined immunodeficiency mouse, which is the most suitable animal model of RA for the evaluation of treatment strategy in vivo. In addition, Ad-FADD-induced apoptosis was limited to cells of the synovium tissue and did not affect chondrocytes. Our results strongly suggest that FADD gene transfer can induce apoptosis of RA synoviocytes both in vitro and in vivo, suggesting that FADD gene transfer might be effective in the treatment of RA.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Purification and primary structure of a macromolecular-translocation inhibitor II of glucocorticoid-receptor binding to nuclei from rat liver. Inhibitor II is the 11.5-kDa Zn2+-binding protein (parathymosin).

The nuclear binding of the activated glucocorticoid-receptor (GR) is inhibited by endogenous macromolecules in vitro. Previously, we have separated the inhibitors into three species (MTI-I, MTI-II and MTI-III). In this study, we purified the most potent of the three species (MTI-II) from the livers of adrenalectomized rats to apparent homogeneity as judged by two-dimensional PAGE. Purified MTI-II inhibits GR binding to DNA containing glucocorticoid-response elements. To obtain the amino acid sequence of MTI-II, we digested the MTI-II with endopeptidases. The N-terminal amino acid sequences of the four digested fragments indicated that MTI-II is an 11.5-kDa Zn2+-binding protein (ZnBP, also known as parathymosin). Furthermore, we purified ZnBP to apparent homogeneity and found that it also inhibits GR binding to nuclei. ZnBP is known to be an abundant acidic protein involved in cell proliferation, and interacts with histone H1 or key enzymes of carbohydrate metabolism via its acidic domain. We also showed that the inhibition of GR binding to nuclei is mediated by the acidic domain of MTI-II (ZnBP, parathymosin) and that GR binds to the MTI-II affinity matrix. Our findings add a new biological function, i.e. the inhibition of GR binding to nuclei and DNA, to this ZnBP. Moreover, our findings suggest that the abundant acidic protein is involved in glucocorticoid action.

Adrenalectomy↗
PubMed2000

Distribution of amyloid beta protein precursor in the Alzheimer's disease brain.

In order to clarify the distribution and pathological changes of the amyloid beta protein precursor (betaAPP), 10 Alzheimer's disease (AD) brains and seven normal control brains were examined by immunocytochemistry and in situ hybridization histochemistry. All betaAPP isoforms were distributed evenly in neuronal cell bodies and their axons and dendrites. The betaAPP-positive neuronal processes showed mesh-like networks. In AD brains, betaAPP-positive neurons and mesh-like networks were generally decreased in spite of some intensely labeled neurons. All betaAPP isoforms accumulated in neuronal processes, dystrophic neurites and senile plaques. In situ hybridization histochemistry confirmed that all isoforms of betaAPP were expressed in neurons in control brains. In AD brains, the betaAPP mRNA signal was generally decreased besides some intense signal neurons corresponding to immunostaining findings. Few astrocytes expressed betaAPP. Thus, uniform expression and distribution of betaAPP were disturbed in AD brains showing uneven decreases or increases of neuronal betaAPP expression in individual neurons and betaAPP accumulation in neurons, neuronal processes and abnormal structures including dystrophic neurites, senile plaques and neurofibrillary tangles.

Aged↗
PubMed2000

Clinicopathological study of pleomorphic xanthoastrocytoma: correlation between histological features and prognosis.

The correlation between histopathological characteristics and prognosis was studied in six cases of pleomorphic xanthoastrocytomas (PXA) found in five patients. With regard to the duration from onset to the resection of the tumor, and the postoperative course, three cases had a favorable prognosis, although one case fatally recurred and in another, serial CT showed rapid tumor growth for 3 years. The histological characteristics of the favorable group of PXA comprised remarkable degeneration, low mitotic activity and a low MIB-1 labeling index. In contrast, the characteristics of the latter two cases of PXA rarely showed degeneration, had atypical mitoses, increasing mitotic activity and a higher MIB-1 labeling index, which indicates that the findings of degeneration, atypical mitoses, mitotic activity and MIB-1 labeling index correlate with the biological behavior of PXA. However, with regard to histological appearance and clinical course, PXA are tumors with a wide range of biological behavior.

Adolescent↗
PubMed2000

Functional modulation of the mineralocorticoid receptor by cis-diamminedichloroplatinum (II).

BACKGROUND: Renal salt wasting and hypotension are some of the frequent complications in patients treated with cis-diamminedichloroplatinum (II) (cDDP), and it is suggested that cDDP produces an abnormality in the renin-angiotensin system. However, not only the underlying mechanism but also prophylactic treatment of this cDDP toxicity remains unknown. In the present study, we investigated the molecular mechanism of this cDDP-induced disturbance of renal sodium handling with focusing on the effect of cDDP on mineralocorticoid receptor (MR) function. METHODS: The effect of cDDP was studied on nuclear translocation, DNA binding activity, and transactivation function of the MR. RESULTS: In a transient transfection assay, cDDP suppressed MR-dependent reporter gene expression. This cDDP-mediated repression of MR function, at least in part, is suggested to be due to the generation of reactive oxygen species and a subsequent decrease in ligand-dependent nuclear translocation and suppression of the interaction with DNA of the MR. This redox-dependent repression of MR function both in vitro and in vivo was reversed by treatment with reducing reagents. Moreover, cDDP, most possibly via formation of DNA adducts, inhibited MR-DNA interaction in a redox-independent fashion. CONCLUSIONS: MR function is impaired by cDDP at multiple levels, via redox-dependent and -independent mechanisms.

Animals↗
PubMed2000

Combined effects of inhaled nitric oxide and positive end-expiratory pressure during mechanical ventilation in acute respiratory distress syndrome.

We studied the combined effects of inhaled nitric oxide (INO) and positive end expiratory pressure (PEEP) during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Eleven patients received 0 and 4 parts per million of INO in random order for 30 min at PEEP levels of 0, 5, and 10 cm H2O. Respiratory and cardiovascular parameters were measured. The addition of INO and PEEP significantly improved arterial oxygenation (p < 0.005 and p < 0.0001, respectively). The combined effect of INO and PEEP on arterial oxygenation was remarkable during 10 cm H2O PEEP. There was synergistic effect on arterial oxygenation by combining INO and 10 cm H2O PEEP. The present study showed that the combination of INO and 10 cm H2O PEEP enhanced arterial oxygenation in patients with ARDS.

Administration, Inhalation↗