Search PubMed⌕ Search

Biomedical subjects

M Koizumi

Publications and source records attributed to M Koizumi.

At least 19 recordsLinked to original sources
PubMed2000

Molecular recognition of cAMP by an RNA aptamer.

Two classes of RNA aptamers that bind the second messenger adenosine 3',5'-cyclic monophosphate (cAMP; 1) were isolated from a random-sequence pool using in vitro selection. Class I and class II aptamers are formed by 33- and 31-nucleotide RNAs, respectively, and each is comprised of similar stem-loop and single-stranded structural elements. Class II aptamers, which dominate the final selected RNA population, require divalent cations for complex formation and display a dissociation constant (K(D)) for cAMP of approximately 10 microM. A representative class II aptamer exhibits substantial discrimination against 5'- and 3'-phosphorylated nucleosides such as ATP, 5'-AMP, and 3'-AMP. However, components of cAMP such as adenine and adenosine also are bound, indicating that the adenine moiety is the primary positive determinant of ligand binding. Specificity of cAMP binding appears to be established by hydrogen bonding interactions with the adenine base as well as by steric interactions with groups on the ribose moiety. In addition, the aptamer recognizes 8,5'-O-cycloadenosine (2) but not N(3), 5'-cycloadenosine (3), indicating that this RNA might selectively recognize the anti conformation of the N-glycosidic bond of cAMP.

Adenosine Triphosphate↗
PubMed2000

General asymmetric hydrogenation of hetero-aromatic ketones

trans-RuCl(2)[(R)-xylbinap][(R)-daipen] or the S,S complex acts as an efficient catalyst for asymmetric hydrogenation of hetero-aromatic ketones. The hydrogenation proceeds with a substrate-to-catalyst molar ratio of 1000-40000 to give chiral alcohols in high ee and high yield. The enantioselectivity appears to be little affected by the properties of the hetero-aromatic ring. This method allows for asymmetric synthesis of duloxetine, an inhibitor of serotonin and norepinephrine uptake carriers.

Journal Article↗
PubMed2000

Selective hydrogenation of benzophenones to benzhydrols. Asymmetric synthesis of unsymmetrical diarylmethanols

[reaction: see text] trans-RuCl2[P(C6H4-4-CH3)3]2(NH2CH2CH2NH2) acts as a highly effective precatalyst for the hydrogenation of a variety of benzophenone derivatives to benzhydrols that proceeds smoothly at 8 atm and 23-35 degrees C in 2-propanol containing t-C4H9OK with a substrate/catalyst ratio of 2000-20000. Use of a BINAP/chiral diamine Ru complex effects asymmetric hydrogenation of various ortho-substituted benzophenones and benzoylferrocene to chiral diarylmethanols with consistently high ee.

Journal Article↗
PubMed2000

Ascites of severe acute pancreatitis in rats transcriptionally up-regulates expression of interleukin-6 and -8 in vascular endothelium and mononuclear leukocytes.

The molecular mechanisms that link acute pancreatitis and multiple organ failure remain unknown. We examined the effect of ascitic fluids prepared from rats with experimental necrotizing pancreatitis on the expression of interleukin (IL) -6 and IL-8 in human umbilical vein endothelial cells (HUVEC) and human monocytic THP-1 cells. Incubation of HUVEC or THP-1 cells with the ascitic fluids resulted in a concentration-dependent up-regulation of the cytokine expression with comparable mRNA induction. Electrophoretic mobility shift assay revealed that the ascitic fluids increased the nuclear factor-kappaB (NF-kappaB) and NF-IL6 binding activities. Intraperitoneal injection of ascitic fluids into healthy rats induced the activation of NF-kappaB in the infiltrating leukocytes in the lung. Our results suggested that ascitic fluids may play a role in the pathophysiology of severe acute pancreatitis through the activation of transcription factors and consequent cytokine productions in distant organs.

Animals↗
PubMed2000

Interference from irrelevant features on visual discrimination by macaques (Macaca fuscata): a behavioral analogue of the human Stroop effect.

To study the operation of selective attention in a conflict situation with automatic processes, we trained 4 Japanese macaques (Macaca fuscata) extensively on a manual go/no-go task. The monkey had to discriminate either the color, shape, motion direction, or location of a visual stimulus. In each trial, the behavioral meaning of the relevant feature (go or no-go) could either be congruent or incongruent with irrelevant features of the same stimulus. Reaction times were slowed, and error rates increased when irrelevant stimulus features were incongruent with the required response. The effects were obtained when the monkey attended to the color, shape, or motion direction, but not when it attended to the location of the stimulus. The effects were cumulative so that the interference from 1 incongruent feature was smaller than that from 2 incongruent features. We propose that the present paradigm provides a behavioral analogue of the human Stroop effect.

Analysis of Variance↗
PubMed2000

Angiotropic lymphoma: proliferation of B cells in the capillaries of cutaneous angiomas.

We report a 52-year-old patient with cutaneous angiomas on the trunk in association with angiotropic lymphoma involving the nervous system. The lesional skin showed proliferation of atypical B cells in the capillaries. The diagnosis of angiotropic lymphoma with neurological deficits is often difficult before death. Thus, skin biopsy in this case proved to be diagnostic of the central nervous system disease without the risk of brain biopsy. The diagnosis of angiotropic lymphoma in the future may be achievable by biopsy of coincidental angiomas.

Biopsy↗
PubMed2000

[An early phase II trial combining cisplatin, carboplatin and vindesine in patients with inoperable non-small cell lung cancer].

We conducted an early phase II trial of advanced non-small cell lung cancer (NSCLC) to evaluate the response efficacy of a combination of cisplatin (CDDP), carboplatin (CBDCA) and vindesine (VDS). The twenty-four patients in the study had had no previous treatment. CDDP (15 mg/m2), CBDCA (200 mg/m2) and VDS (3 mg/m2) were administered on Day 1, CDDP (15 mg/m2) was administered on Days 2-5, and VDS (3 mg/m2) was administered on Day 8. We observed 9 partial responses (PR), with a total response rate of 39%. The overall median survival was 72 weeks, and the 1-year survival rate was 57%. Major toxicities were hematologic; leukopenia of grades 3 and 4 occurred in 25% patients, and thrombocytopenia occurred in 21%. Therefore, the combination of CBDCA with CDDP and VDS chemotherapy was effective against inoperable NSCLC with tolerable toxicities and a favorable median survival time.

Adenocarcinoma↗
PubMed2000

[Influence of the radioactive strontium (89Sr) using for nuclear medical radiation therapy upon radioactive draining-water system].

PURPOSE: Strontium-89 chloride (89Sr) is a new radiopharmaceutical that provides effective pain relief for metastatic bone lesions, and is expected to be available soon in the palliative management for metastatic bone pain in Japan. Because of relatively long physical half life (50.5 days), 89Sr may affect to the radioactive draining-water system by exceeding the limits of activity concentration for radioactive drain. In this article, the influence of 89Sr use on the radioactive drainage system was simulated. METHODS: The standard tank capacity of drainage and draining frequency was determined from the results of questionnaire carried out for the nationwide medical and research institutes where radioisotope treatment are performed. On the assumption that 89Sr of 148 MBq for one therapy was used twice a week and several common radionuclides were used as the same activity as used at Chiba Cancer Center, the influence of 89Sr was estimated. The calculation was performed using the activity contamination ration into the draining-water system of each radionuclide of 0.01, which was legally determined. RESULTS: The simulation revealed that the sum of the contamination ratios of individual radionuclides exceeded a legal value of 1.0 in standard drainage with the capacity of 5 m3 and 10 m3 and draining frequency of 7 times per year. The actual contamination ratios of common radiopharmaceuticals measured at Chiba Cancer Center ranged from 1/100 to 1/1000 of the legal values. CONCLUSION: It is necessary that the legal value of activity contamination ratios into the draining-water system should be reassessed before starting 89Sr therapy.

Bone Neoplasms↗
PubMed1999

Radiotherapy of early tongue cancer in patients less than 40 years old.

PURPOSE: To evaluate the results of treatment for early mobile tongue cancer in patients less than 40 years. METHODS AND MATERIALS: Between January 1967 and September 1992, 70 patients less than 40 years old (young age group) with early tongue cancer (T1-2N0M0) were treated with low-dose-rate (LDR) interstitial radiotherapy at the Osaka University Hospital (OUH). All patients had a minimum 2-year follow-up (median: 13 years). External radiotherapy (median: 30 Gy) was combined in 25 cases. The treatment results were compared with those for two older age groups (middle age: 40-64 years old; old age: 65 years old or more). RESULTS: The 5-year probability of cause-specific survival (CSS) rate for the young age group was 80%, which was not significantly different from the two older groups: 81% for middle age and 71% for old age. However, male patients of young age showed significantly worse rates than those of middle and old age (p = 0.02). The 5-year local control rate for the young age group was 78%. It was not significantly different from the two older groups: 81% for middle age and 70% for old age. The incidence of regional lymph node metastasis was 32% for T1, 48% for T2, 56% for males, and 24% for females. The regional failure rate of young males was significantly higher than those of the two older groups: 32% for middle and 22% for old age (p = 0.001). CONCLUSION: The overall treatment results for patients with early tongue cancer less than 40 years old were not worse than those of older age groups. However, male gender was a risk factor for lymph node metastasis and CSS.

Adult↗
PubMed1999

Crystal structure of coagulation factor IX-binding protein from habu snake venom at 2.6 A: implication of central loop swapping based on deletion in the linker region.

Coagulation factor IX-binding protein (IX-bp) isolated from the venom of the habu snake (Trimeresurus flavoviridis) is a disulfide-linked heterodimer consisting of homologous subunits A and B. The structure of IX-bp has been solved by X-ray crystallography at 2.6 A resolution to a crystallographic R -value of 0.181. The main-chain fold of each subunit is homologous to the carbohydrate-recognition domain of C-type lectins (C-type CRDs) except for the extended central loop. The structure is almost identical with that of factors IX and X-binding protein (IX/X-bp) as expected from the high level of amino acid sequence homology. The functional difference in ligand recognition from IX/X-bp must reside in the amino acid differences. A continuity of different amino acid residues located from the C-terminal of the second alpha-helix to the following loop forms the local conformational difference in this region between the two proteins. This loop participates in the formation of the concave surface between the two subunits, the putative binding site for the Gla-domain (gamma-carboxyglutamic acid-containing domain) of the coagulation factors. Another difference between the two proteins is in the relative disposition of subunits A and B. When the B subunits are superimposed, about a 6 degrees rotation is required for the superposition of the A subunits. A calcium ion links the second alpha-helix region to the C-terminal tail in each subunit and helps to stabilize the structure for Gla-domain binding. The interface created by the central loop swapping in the dimer IX-bp is almost identical with that seen within the monomeric C-type CRDs. This dimer forms as the result of the amino acid deletion in the linker region of the central loop of the original C-type lectins. Such a dimerization disrupts the lectin active site and creates a Gla-domain binding site, imparting functional diversity.

Amino Acid Sequence↗
PubMed1999

Perioperative fractionated high-dose rate brachytherapy for malignant bone and soft tissue tumors.

PURPOSE: To investigate the viability of perioperative fractionated HDR brachytherapy for malignant bone and soft tissue tumors, analyzing the influence of surgical margin. METHODS AND MATERIALS: From July 1992 through May 1996, 16 lesions of 14 patients with malignant bone and soft tissue tumors (3 liposarcomas, 3 MFHs, 2 malignant schwannomas, 2 chordomas, 1 osteosarcoma, 1 leiomyosarcoma, 1 epithelioid sarcoma, and 1 synovial sarcoma) were treated at the Osaka University Hospital. The patients' ages ranged from 14 to 72 years (median: 39 years). Treatment sites were the pelvis in 6 lesions, the upper limbs in 5, the neck in 4, and a lower limb in 1. The resection margins were classified as intracapsular in 5 lesions, marginal in 5, and wide in 6. Postoperative fractionated HDR brachytherapy was started on the 4th-13th day after surgery (median: 6th day). The total dose was 40-50 Gy/7-10 fr/4-7 day (bid) at 5 or 10 mm from the source. Follow-up periods were between 19 and 46 months (median: 30 months). RESULTS: Local control rates were 75% at 1 year and 48% in 2 years, and ultimate local control was achieved in 8 (50%) of 16 lesions. Of the 8 uncontrolled lesions, 5 (63%) had intracapsular (macroscopically positive) resection margins, and all the 8 controlled lesions (100%) had marginal (microscopically positive) or wide (negative) margins. Of the total, 3 patients died of both tumor and metastasis, 3 of metastasis alone, 1 of tumor alone, and 7 showed no evidence of disease. Peripheral nerve palsy was seen in one case after this procedure, but no infection or delayed wound healing caused by tubing or irradiation has occurred. CONCLUSION: Perioperative fractionated HDR brachytherapy is safe, well tolerated, and applicable to marginal or wide surgical margin cases.

Adolescent↗
PubMed1999

Effect of electric field on physical states of cell-associated water in germinating morning glory seeds observed by 1H-NMR.

Morning glory seeds in dry conditions (0.099 g H2O/dry wt.) were exposed to electric fields and germinated. The physical state of water in the germinating seeds of both control and exposed groups were examined using 1H-NMR spectroscopy and NMR microscopy. Three water fractions were observed which were characterized by different relaxation times (T1) and chemical shifts. The average region containing long T1 fractions was approximately 50 micrometer in diameter and consisted of half-permeable barriers. The maximum intracellular water transport rate was 2.3x10-5 cm2/s. The treatment with electric field (500 kV/m for 60 min) increased the fraction with the shortest T1 and decreased that with the longest T1. Because the total water content in the treated seeds (3.4 g H2O/dry wt.) was similar to that in the untreated seeds (3.9 g H2O/dry wt.), the treated seeds held more water in a condition in restricted motion than the untreated seeds. It is thought that the membrane systems were affected by the electric polarization which led to an unusual accumulation of water and the hydration of stored macromolecules during the imbibition process. This set of events led to excessive swelling of stored macromolecules, resulting in the disruption of membrane systems and irregular organization of tissue structures.

Cell Membrane↗
PubMed1999

A low-resolution structure of rice dwarf virus determined by ab initio phasing.

Rice dwarf virus crystals belong to space group I222 with cell parameters a = 770 (2), b = 795 (5), c = 814 (5) A and alpha = beta = gamma = 90 degrees. The unit cell of the crystal contains two viruses at the origin and body-centred positions. Using data synthesized from a rice dwarf virus model crystal in the space group I222, the possibility of ab initio phasing was thoroughly examined. The centric nature of the initial phases was unexpectedly broken by extensive iteration of the non-crystallographic symmetry averaging. The structure of rice dwarf virus was then solved with ab initio phasing up to 20 A resolution. The triangulation number determined by the present study is T = 13, which is different from the triangulation number, T = 9, previously determined by electron microscopy [Uyeda & Shikata (1982). Ann. Phytopathol. Soc. Jpn, 48, 295-300].

Capsid↗
PubMed1999

Different expression patterns of nitric oxide synthase isozymes in various gynecological cancers.

The expression of nitric oxide synthase (NOS) in human gynecological cancers, including ovarian cancers, uterocervical cancers, and endometrial cancers for example, was examined by the reverse transcriptase/polymerase chain reaction, coupled with Southern hybridization and by immunohistochemistry. Nitric oxide synthase II (NOS II), an inducible form, was expressed in more than 90% of the cancers. Nitric oxide synthase I (NOS I), a neuronal form, was expressed in 58% of all the ovarian cancers, in which the serous type is found more frequently (5 out of 7) than the mucinous type (2 out of 6), and in all clear-cell cancers. The frequency of NOS I expression in uterocervical cancers and endometrial cancers was relatively low. Nitric oxide synthase III (NOS III), an endothelial form, was detected in 25% of ovarian and 33% of endometrial cancers, while no expression was detected in uterocervical cancers. In terms of cancer types, all clear-cell adenocarcinomas and most of the serous-type adenocarcinomas expressed both NOS I and NOS II, while most uterine squamous carcinomas and endometrial adenocarcinomas expressed only NOS II. However, there was no correlation between the frequency of NOS expression and patients' age or the clinical stage of the disease. Since NO increases vascular permeability and blood flow, the high frequency of NOS expression in gynecological cancers may serve to stimulate and promote tumor growth.

Blotting, Southern↗
PubMed1999

Helicobacter pylori-dependent ceramide production may mediate increased interleukin 8 expression in human gastric cancer cell lines.

BACKGROUND & AIMS: Helicobacter pylori adheres to gastric epithelial cells, activates nuclear factor kappaB (NF-kappaB), and stimulates interleukin (IL)-8 production, but the responsible molecular mechanisms remain largely unknown. Because several studies have shown that sphingolipids are involved in a number of signaling pathways, including NF-kappaB activation, we investigated the possible role of sphingolipids in the regulation of IL-8 expression in Kato III and AGS cells. METHODS: IL-8 production in the conditioned media was quantified by enzyme immunoassay. Induction of messenger RNA (mRNA) was assessed by Northern blot analysis. Activation and binding activity of transcription factors were examined by luciferase assay and electrophoretic mobility shift assay, respectively. Intracellular levels of ceramide were quantified by diacylglycerol kinase assay. RESULTS: A cell-permeable ceramide analogue (C2-ceramide) increased IL-8 expression with comparable mRNA induction. This effect was mimicked by sphingomyelinase, but not by phospholipase A2 or phospholipase C. C2-ceramide induced IL-8 gene transcription mainly through activation of NF-kappaB because mutation of the NF-kappaB-binding site completely abrogated the induction of luciferase activity. Direct contact of live H. pylori with epithelial cells increased the intracellular concentration of ceramide. CONCLUSIONS: The results suggest a novel role of the sphingomyelin-ceramide pathway, at least in part through NF-kappaB, in IL-8 production induced by H. pylori infection in gastric epithelial cells.

Ceramides↗
PubMed1999

Communication between the axillary and radial nerves in the human upper arm.

The communication between the axillary (Ax) and the radial (R) nerves, which was observed in eight upper arms from 602 arms of 301 Japanese cadavers, was studied to determine its origin and distribution. The brachial plexus and spinal segments contributing to the Ax and R in all cases where communication occurred had no distinct differences from those in cases having no communication. According to the direction, the communication is divided into two groups: the communication from the Ax to R (7 cases) and vice versa (2 cases). One specimen had both groups of communication. The origin of communicating branches in these groups extended into the overlapping area (C5 + 6) of the origin of the Ax with that of the R, mainly from the ventral layer of the posterior cord from C6. The distribution of the communicating branch varied in development according to specimens. The communication from the Ax to R has a tendency to invade, from proximally to distally, the distribution of the muscular branches of the R to the radial extensor muscles of the forearm including the supinator muscle. However, the development into the cutaneous branches has no distinct inclination. These findings in humans and some other comparative anatomical descriptions show that in phylogeny the radial extensor muscles of the forearm have a different origin from other extensor muscles of the forearm and have a close relationship with the Ax. Therefore, the communication between the Ax and R holds an important clue in clarifying the morphological significance of the extensor nerves and muscles of the forearm.

Arm↗