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Biomedical subjects

K Okada

Publications and source records attributed to K Okada.

At least 271 records · Page 15Linked to original sources

[Malignant islet cell tumor of the pancreas with multiple liver metastases effectively treated by transcatheter arterial embolization with degradable starch microspheres--a case report].

A 57-year-old woman underwent distal pancreatectomy for malignant islet cell tumor of the pancreas in 1991. One year later, multiple liver metastases appeared. Although three transcatheter arterial embolizations (TAE) with spongel and nine ethanol injections were performed over seven years, the tumors were growing gradually. Therefore, TAE with degradable starch microspheres (DSM) was selected. Under angiography, TAE of the left hepatic artery was done using 900 mg of DSM following injection of Farumorubicin (20 mg), Lipiodol (3 ml) and cisplatin (90 mg). The tumors in the embolized hepatic area were remarkably decreased in size, and satisfactory local control was obtained. Thereafter, TAE with DSM was carried out twice, and she is still living with outpatient treatment. Thus, it is suggested that TAE with DSM could be a promising, alternative therapeutic modality for liver metastases from malignant islet cell tumor of the pancreas.

Antineoplastic Combined Chemotherapy Protocols↗

[Endonasal transsphenoidal surgery under local anesthesia for elderly patient with pituitary tumor: case report].

We present a surgical case under local anesthesia of an 88-year-old woman suffering from visual disturbance caused by pituitary adenoma. Magnetic resonance (MR) imaging showed a large pituitary tumor with suprasellar extension compressing the chiasmatic nerve. Neither she nor her family would agree to surgical therapy. However, when we proposed surgery under local anesthesia, they accepted it. Partial removal of the tumor via the endonasal transsphenoidal approach was carried out, uneventfully. The nasal surface was infiltrated with 4%-Xylocaine prior to the ordinary xylocaine injection to the nasal mucosa. The patient did not complain of any pain associated with the surgical procedure, including saline injection to the subarachnoid space through spinal drainage. The postoperative course was fine except for the temporarily appearance of diabetes insipidus. Postoperative MR imaging showed complete relief of compression to the chiasmatic nerve. Her visual field was improved dramatically. Endonasal transsphenoidal surgery under local anesthesia is thought to be one of the most useful methods of choice, especially in cases of elderly patient with pituitary tumor.

Adenoma↗

[Two cases of nephrogenic adenoma in the bladder diverticulum].

We report two cases of a nephrogenic adenoma in the bladder diverticulum. The first patient was an 81-year-old man with gross hematuria. Cystoscopy revealed bladder diverticulum and a papillary tumor within. Bladder diverticulectomy was performed and the histopathological diagnosis was a nephrogenic adenoma. The second patient was a 50-year-old man with gross hematuria and dysuria. Transabdominal ultrasound revealed bladder diverticulum. Transurethral coagulation of the bladder diverticulum was performed. Then three papillary tumors were detected, and were resected transurethrally. The histopathological diagnosis was a nephrogenic adenoma. These are the first and second cases of a nephrogenic adenoma in the bladder diverticulum reported in Japan.

Adenoma↗

[Evaluation of prostate cancer using FDG-PET].

The clinical usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) was examined in 54 patients with prostate cancer. FDG accumulation was positive in 38 of 54 the prostates (70%), 3 of 8 the lymph node metastases (38%) and 10 of 16 the bone metastases (63%), which suggested that FDG-PET is not superior to other conventional imaging methods as a tool for tumor detection. On the other hand, a quantitative value for FDG uptake in the prostate, expressed as a standardized uptake value (SUV), significantly correlated to the histological grade, clinical stage and serum PSA of the patients. A decrease of SUV was observed in all the patients who responded to endocrine treatment, and the patients with high pre-treatment SUV were shown to be at the risk for disease progression after initial treatment. The present results indicated that FDG-PET could provide us with useful prognostic information for the patients with prostate cancer by evaluating the malignant potential of the tumor.

Bone Neoplasms↗

Nutritional therapy of chronic hepatitis by whey protein (non-heated).

In an open study the clinical efficacy of milk serum (whey) protein (Immunocal; cysteine content: 7.6-fold higher than that of casein) isolated from fresh milk and purified without heating was evaluated in 25 patients with chronic hepatitis B or C. Immunocal (12 g as protein) food (mousse) was given twice a day, in the morning and evening, for 12 weeks (test period). Casein (12 g as protein) food (mousse) was similarly given for two weeks prior to the start of the supplement with Immunocal food (induction period) and for four weeks after the end of the supplement with Immunocal food (follow-up period). Serum alanine aminotransferase (ALT) activity was reduced, and plasma glutathione (GSH) levels increased in six and five of eight patients with chronic hepatitis B, respectively, 12 weeks after the start of the supplement with Immunocal food. Serum lipid peroxide levels significantly decreased, and interleukin (IL)-2 levels and natural killer (NK) activity significantly increased. However, there were no significant Immunocal-related changes in 17 patients with chronic hepatitis C. These findings suggest that the long-term supplement with Immunocal alone may be effective for improving liver dysfunctions in patients with chronic hepatitis B.

Adult↗

The formation of explosive compounds in bitumen/nitrate mixtures

Ignition of various bitumen/nitrate mixtures was examined using a new method of thermal analysis, developed in the present study, in order to determine the self-ignition temperatures (SIT) of the sample materials. The effects on the SIT of transition elements, particularly silver, and the heating rates were examined. The same bitumen/nitrate mixtures were prepared by mixing bitumen, NaNO(3), Ni(NO(3))(2) and either AgNO(3) or AgI. The sample heating rates were in the range from 0.5 to 4.0 degrees C/min. In the present work, SIT was found to be independent on the heating rate when AgI is added, while SIT was found to depend on the heating rate when AgNO(3) was added. The activation energy E(a) for the ignition of bitumen/nitrate mixtures has been calculated to be 30 kJ/mol. The suspected initiator of the ignition is thought to be silver fulminates or related compounds.

Journal Article↗

Surface Acidity and Hydrophilicity of Coprecipitated Al(2)O(3)-SiO(2) Xerogels Prepared from Aluminium Nitrate Nonahydrate and Tetraethylorthosilicate.

Amorphous aluminosilicate xerogels with various chemical compositions were prepared by coprecipitation, and their surface acidity and hydrophilicity were investigated by NH(3) gas temperature programed desorption (TPD), water vapor adsorption-desorption isotherms, and (27)Al magic angle spinning nuclear magnetic resonance (MAS NMR). The xerogels were synthesized by adding conc. NH(4)OH to an ethanol solution of calculated amounts of aluminium nitrate nonahydrate and tetraethylorthosilicate, and calcined at 300 degrees C for 4 h. All the NH(3) TPD spectra of the xerogels showed similar asymmetric peak profiles at around 200 degrees C tailing to the higher temperature side. The amount of acidity evaluated from the peak area of the TPD spectra showed a maximum at around 10 mol% Al(2)O(3) composition. The change as a function of composition showed a good correlation with the total amount of four and five coordinated Al atoms in the xerogels deduced from the (27)Al MAS NMR spectra. The water vapor adsorption isotherms of the xerogels were all of type IV irrespective of the composition. The maximum amounts of water vapor adsorbed by these xerogels were about 600-700 ml(STP)/g and were relatively high compared with those for various other adsorbents reported so far. Since the thickness of the adsorbed water vapor layer of the xerogels in the low relative pressure region increased with increasing Al(2)O(3) content, the surface of the xerogels is considered to become more hydrophilic with increasing Al(2)O(3) content of the xerogels. Copyright 1999 Academic Press.

Journal Article↗

Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23 kDa/proliferation-associated gene product.

Heme-binding protein 23 kDa (HBP23), a rat isoform of human proliferation-associated gene product (PAG), is a member of the peroxiredoxin family of peroxidases, having two conserved cysteine residues. Recent biochemical studies have shown that HBP23/PAG is an oxidative stress-induced and proliferation-coupled multifunctional protein that exhibits specific bindings to c-Abl protein tyrosine kinase and heme, as well as a peroxidase activity. A 2.6-A resolution crystal structure of rat HBP23 in oxidized form revealed an unusual dimer structure in which the active residue Cys-52 forms a disulfide bond with conserved Cys-173 from another subunit by C-terminal tail swapping. The active site is largely hydrophobic with partially exposed Cys-173, suggesting a reduction mechanism of oxidized HBP23 by thioredoxin. Thus, the unusual cysteine disulfide bond is involved in peroxidation catalysis by using thioredoxin as the source of reducing equivalents. The structure also provides a clue to possible interaction surfaces for c-Abl and heme. Several significant structural differences have been found from a 1-Cys peroxiredoxin, ORF6, which lacks the C-terminal conserved cysteine corresponding to Cys-173 of HBP23.

Amino Acid Sequence↗

4-Hydroxy-2-nonenal-mediated impairment of intracellular proteolysis during oxidative stress. Identification of proteasomes as target molecules.

Oxidative stress is associated with important pathophysiological events in a variety of diseases. It has been postulated that free radicals and lipid peroxidation products generated during the process may be responsible for these effects because of their ability to damage cellular components such as membranes, proteins, and DNA. In the present study, we provide evidence that oxidative stress causes a transient impairment of intracellular proteolysis via covalent binding of 4-hydroxy-2-nonenal (HNE), a major end product of lipid peroxidation, to proteasomes. A single intraperitoneal treatment with the renal carcinogen, ferric nitrilotriacetate, caused oxidative stress, as monitored by accumulation of lipid peroxidation products and 8-hydroxy-2'-deoxyguanosine, in the kidney of mice. In addition, transient accumulation of HNE-modified proteins in the kidney was also found by competitive enzyme-linked immunosorbent assay and immunohistochemical analyses. This and the observation that the HNE-modified proteins were significantly ubiquitinated suggested a crucial role of proteasomes in the metabolism of HNE-modified proteins. In vitro incubation of the kidney homogenates with HNE indeed resulted in a transient accumulation of HNE-modified proteins, whereas the proteasome inhibitor significantly suppressed the time-dependent elimination of HNE-modified proteins. We found that, among three proteolytic activities (trypsin, chymotrypsin, and peptidylglutamyl peptide hydrolase activities) of proteasomes, both trypsin and peptidylglutamyl peptide hydrolase activities in the kidney were transiently diminished in accordance with the accumulation of HNE-modified proteins during oxidative stress. The loss of proteasome activities was partially ascribed to the direct attachment of HNE to the protein, based on the detection of HNE-proteasome conjugates by an immunoprecipitation technique. These results suggest that HNE may contribute to the enhanced accumulation of oxidatively modified proteins via an impairment of ubiquitin/proteasome-dependent intracellular proteolysis.

Adenosine Triphosphate↗

Effects of electrical stimulation of thalamic nucleus submedius and periaqueductal gray on the visceral nociceptive responses of spinal dorsal horn neurons in the rat.

Electrical stimulation of the nucleus submedius (Sm) has been shown to suppress the viscerosomatic reflex (VSR), which is evoked by colorectal distension (CRD). We have examined the effects of focal electrical stimulation (0.3 ms, 50 Hz, 100 microA, 10 s) of the Sm and the periaqueductal gray (PAG) on the excitatory responses evoked by CRD in spinal dorsal horn neurons within the L6-S1 region in the urethane-anesthetized Wistar rats. Extracellular recordings were made from 32 spinal excitatory CRD responses. All of these neurons were convergent neurons with cutaneous receptive fields. The majority of the neurons (27/32) were wide dynamic range (WDR) neurons (responding to noxious and non-noxious cutaneous stimuli) while the remaining five neurons were nociceptive specific (NS) neurons (responding only to noxious cutaneous stimuli). The effects of electrical stimulation applied to 28 sites within the Sm were assessed for spinal neurons. Electrical stimulation in seven sites within the Sm (25%) inhibited the CRD excitatory response of dorsal horn neurons, while in two sites (7%) the same stimulation yielded facilitation. Electrical stimulation in the majority of the sites in the Sm (19/28, 68%) did not affect spinal excitatory CRD responses. On the other hand, electrical stimulation of the PAG clearly inhibited 20 of 22 (90%) CRD excitatory responses. These results suggest that the majority of Sm neurons may suppress VSR activity at a supraspinal reflex center rather than via a descending inhibition of spinal visceral nociceptive transmission, as is the case for the PAG.

Animals↗

Chlorophyll b and phycobilins in the common ancestor of cyanobacteria and chloroplasts.

Photosynthetic organisms have a variety of accessory pigments, on which their classification has been based. Despite this variation, it is generally accepted that all chloroplasts are derived from a single cyanobacterial ancestor. How the pigment diversity has arisen is the key to revealing their evolutionary history. Prochlorophytes are prokaryotes which perform oxygenic photosynthesis using chlorophyll b, like land plants and green algae (Chlorophyta), and were proposed to be the ancestors of chlorophyte chloroplasts. However, three known prochlorophytes (Prochloron didemni, Prochlorothrix hollandica and Prochlorococcus marinus) have been shown to be not the specific ancestors of chloroplasts, but only diverged members of the cyanobacteria, which contain phycobilins but lack chlorophyll b. Consequently it has been proposed that the ability to synthesize chlorophyll b developed independently several times in prochlorophytes and in the ancestor of chlorophytes. Here we have isolated the chlorophyll b synthesis genes (chlorophyll a oxygenase) from two prochlorophytes and from major groups of chlorophytes. Phylogenetic analyses show that these genes share a common evolutionary origin. This indicates that the progenitors of oxygenic photosynthetic bacteria, including the ancestor of chloroplasts, had both chlorophyll b and phycobilins.

Amino Acid Sequence↗

Walking to work and the risk for hypertension in men: the Osaka Health Survey.

BACKGROUND: It is not known whether physical activity is effective in reducing the risk for hypertension. OBJECTIVE: To investigate the association of the duration of the walk to work and leisure-time physical activity with the risk for hypertension. DESIGN: Prospective cohort study. SETTING: Work site in Osaka, Japan. PARTICIPANTS: 6017 Japanese men 35 to 60 years of age with systolic blood pressure less than 140 mm Hg, diastolic blood pressure less than 90 mm Hg, normal glucose intolerance, and no history of hypertension or diabetes at baseline. MEASUREMENTS: Data on physical activity were obtained by using questionnaires. Blood pressure was measured by using a standard technique; a value of at least 160/95 mm Hg was used to diagnose hypertension. RESULTS: During 59,784 person-years of follow-up, 626 cases of hypertension were confirmed. The duration of the walk to work was associated with a reduction in the risk for incident hypertension; multivariate-adjusted relative risks were 1.00 for a walk of 10 minutes or less (reference category), 0.88 (95% CI, 0.75 to 1.04) for an 11- to 20-minute walk, and 0.71 (CI, 0.52 to 0.97) for a walk of 21 minutes or more (P for trend = 0.02). For every 26.3 men who walk more than 20 minutes to work, one case of hypertension will be prevented. CONCLUSIONS: Walking to work and other types of physical activity decreased the risk for hypertension in Japanese men. Regular exercise can prevent hypertension.

Adult↗

Characterization of the transcriptional activator CBF1 from Arabidopsis thaliana. Evidence for cold denaturation in regions outside of the DNA binding domain.

A transcriptional activator, CBF1, from Arabidopsis thaliana, which has the AP2 domain for DNA binding and regulates the cold acclimation response, was overexpressed in Escherichia coli, purified, and characterized. Analyses of the interaction between CBF1 and the C-repeat/dehydration-responsive element by fluorescence measurement showed that CBF1 binds to C-repeat/dehydration-responsive element as a monomer irrespective of the temperature. CD spectra of the intact and truncated CBF1 proteins (1-213, 41-213, 41-157, and 41-146) were measured to examine the temperature-dependent changes of the secondary structure of CBF1. The results suggested that the CBF1 protein has regions exhibiting reversible cold denaturation in the range between 30 and -5 degrees C and also has a region exhibiting thermal denaturation between 40 and 60 degrees C. This cold denaturation occurred in both the N-terminal and acidic regions. The thermal denaturation occurred in the region encompassing the AP2 domain. The difference between the retention time of CBF1 at 4 degrees C and that at 25 degrees C in gel filtration, and the decrease of the sedimentation coefficient, s20,w, caused by the temperature change from 25 to 3 degrees C, strongly suggested that the cold denaturation was accompanied by the extension of the molecule. The possible cold denaturation observed here might be a physiologically important structural response of CBF1 to cold stress.

Arabidopsis↗

Crystallographic characterization of a stress-induced multifunctional protein, rat HBP-23.

HBP-23 is a stress-induced multifunctional rat protein that belongs to a novel family of antioxidant proteins, referred to as peroxiredoxins, and exhibits heme-binding and inhibition of c-Abl protein tyrosine kinase. Recombinant HBP-23 was crystallized by a hanging-drop vapor-diffusion method. The crystals belong to space group P41212 or P43212 with unit-cell dimensions of a = b = 73.47 A, c = 210.37 A and contain two protein molecules in the asymmetric unit. A data set at 2.7-A resolution was collected with a cryo-crystallographic technique. Crystals of selenomethionyl HBP-23 were also obtained under the same conditions.

Animals↗

Membranocystic lesion in lumbar yellow ligament.

STUDY DESIGN: An examination of surgical cases of membranocystic lesions in the lumbar yellow ligament between the fourth and fifth lumbar vertebrae. OBJECTIVES: To report the incidence and pathogenesis of membranocystic lesions of the yellow ligament in surgical specimens. SUMMARY OF BACKGROUND DATA: The membranocystic lesion has been observed not only in membranous lipodystrophy, but also in other conditions. However, there has been no report concerning this lesion in the yellow ligament. METHODS: Forty-four yellow ligaments excised in surgery were histologically reviewed. In eight cases, S-100 expression was investigated. In two cases, ultrastructural findings were examined. RESULTS: Membranocystic lesions were present in 8 (18%) of the 44 cases. The cases with the lesions had undergone surgery for spondylolisthesis (4 cases), sequestration-type disc herniation (2 cases), postradiation status (1 case), and spinal stenosis (1 case). Histologically, in all 8 cases, fibrosis was present around the lesion. In 5 of the 8 cases, chondrocytes were observed adjacent to the lesion, and nuclei positive for S-100 protein were observed in 4 cases. Nuclei of chondrocytes adjacent to the lesion also were positive for S-100 protein. Ultrastructurally, irregularly shaped cystic spaces surrounded by an electron-dense membranous structure, which were identical to those of membranous lipodystrophy, were observed. CONCLUSIONS: These results suggest that degeneration of the chondrocytes has a causal relationship to the formation of membranocystic lesions in the yellow ligament.

Adolescent↗

Simultaneous quantitative determination of cilostazol and its metabolites in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the simultaneous determination of cilostazol, a quinolinone derivative, and its known metabolites OPC-13015, OPC-13213, OPC-13217, OPC-13366, OPC-13269, OPC-13326 and OPC-13388 in human plasma was developed and validated. Cilostazol, its metabolites and two internal standards, OPC-3930 and OPC-13112, were extracted from human plasma by a combination of liquid-liquid and liquid-solid phase extractions, with combined organic solvents of n-butanol, methanol, chloroform, methyl-tert.-butyl ether, and a Sep-Pak silica column. The combined extract was then evaporated and the residue was reconstituted in ammonium acetate buffer (pH 6.5). The reconstituted solution was injected onto a HPLC system and was subjected to reversed-phase HPLC on a 5 microm ODS-80TM column to obtain quality chromatograph and good peak resolution. A gradient mobile phase with different percentages of acetonitrile in acetate buffer (pH 6.5) was used for the resolution of analytes. Cilostazol, its metabolites and the two internal standards were well separated at baseline from each other with resolution factor being 74 and 138. This HPLC method was demonstrated to be specific for all analytes of interest with no significant interference from the endogenous substances of human plasma. The lower limit of quantitation was 20 ng/ml for cilostazol and all metabolites. The method was validated initially for an extended linear range of 20-600 ng/ml for all metabolites and cilostazol, and has been revised later for a linear range of 20-1200 ng/ml for cilostazol and two major and active metabolites OPC-13015 and OPC-13213. The overall accuracy (relative recovery) of this method was established to be 98.5% to 104.9% for analytes with overall precision (CV) being 1.5% to 9.0%. The long-term stability of clinical plasma samples was established for at least one year at -20 degrees C. Two internal standards of OPC-3930 and OPC-13112 were evaluated and validated. However, the data indicated that there was no significant difference for all accuracy and precision obtained by using either OPC-3930 or OPC-13112. OPC-3930 was chosen as the internal standard for the analysis of plasma samples from clinical studies due to its shorter retention time. During the validation standard curves had correlation coefficients greater than or equal to 0.998 for cilostazol and the seven metabolites. These data clearly demonstrate the reliability and reproducibility of the method.

Chromatography, High Pressure Liquid↗

FILAMENTOUS FLOWER, a meristem and organ identity gene of Arabidopsis, encodes a protein with a zinc finger and HMG-related domains.

Distinctive from that of the animal system, the basic plan of the plant body is the continuous formation of a structural unit, composed of a stem with a meristem at the top and lateral organs continuously forming at the meristem. Therefore, mechanisms controlling the formation, maintenance, and development of a meristem will be a key to understanding the body plan of higher plants. Genetic analyses of filamentous flower (fil) mutants have indicated that FIL is required for the maintenance and growth of inflorescence and floral meristems, and of floral organs of Arabidopsis thaliana. FIL encodes a protein carrying a zinc finger and a HMG box-like domain, which is known to work as a transcription regulator. As expected, the FIL protein was shown to have a nuclear location. In situ hybridization clearly demonstrated that FIL is expressed only at the abaxial side of primordia of leaves and floral organs. Transgenic plants, ectopically expressing FIL, formed filament-like leaves with randomly arranged cells at the leaf margin. Our results indicate that cells at the abaxial side of the lateral organs are responsible for the normal development of the organs as well as for maintaining the activity of meristems.

Alleles↗

The crystal structure of pyroglutamyl peptidase I from Bacillus amyloliquefaciens reveals a new structure for a cysteine protease.

BACKGROUND: The N-terminal pyroglutamyl (pGlu) residue of peptide hormones, such as thyrotropin-releasing hormone (TRH) and luteinizing hormone releasing hormone (LH-RH), confers resistance to proteolysis by conventional aminopeptidases. Specialized pyroglutamyl peptidases (PGPs) are able to cleave an N-terminal pyroglutamyl residue and thus control hormonal signals. Until now, no direct or homology-based three-dimensional structure was available for any PGP. RESULTS: The crystal structure of pyroglutamyl peptidase I (PGP-I) from Bacillus amyloliquefaciens has been determined to 1.6 A resolution. The crystallographic asymmetric unit of PGP-I is a tetramer of four identical monomers related by noncrystallographic 222 symmetry. The protein folds into an alpha/beta globular domain with a hydrophobic core consisting of a twisted beta sheet surrounded by five alpha helices. The structure allows the function of most of the conserved residues in the PGP-I family to be identified. The catalytic triad comprises Cys144, His168 and Glu81. CONCLUSIONS: The catalytic site does not have a conventional oxyanion hole, although Cys144, the sidechain of Arg91 and the dipole of an alpha helix could all stabilize a negative charge. The catalytic site has an S1 pocket lined with conserved hydrophobic residues to accommodate the pyroglutamyl residue. Aside from the S1 pocket, there is no clearly defined mainchain substrate-binding region, consistent with the lack of substrate specificity. Although the overall structure of PGP-I resembles some other alpha/beta twisted open-sheet structures, such as purine nucleoside phosphorylase and cutinase, there are important differences in the location and organization of the active-site residues. Thus, PGP-I belongs to a new family of cysteine proteases.

Amino Acid Sequence↗