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Biomedical subjects

M Koizumi

Publications and source records attributed to M Koizumi.

At least 73 records · Page 4Linked to original sources
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↗
PubMed2000

[Beneficial effects of CHOP therapy in a case of intravascular large B-cell lymphoma diagnosed by skin biopsy].

We report a case of intravascular large B-cell lymphoma. A 52-year-old man gradually developed dementia and abnormal behaviors, which were later accompanied by spastic paraplegia and sensory disturbance in his lower limbs. MR imaging of his brain showed high signal intensity lesions on T2 imaging. IMP-SPECT images of the brain showed diffuse reduction of radioisotope uptake. Many skin rashes that looked like senile hemangioma were observed on his body. Several of those were biopsied, and the diagnosis of intravascular large B-cell lymphoma was made because of malignant B lymphocytes filling the vessel lumens in one of the seven biopsy specimens. CHOP therapy was performed and found to be effective for the neurological disorders such as dementia, paraplegia, and sensory disturbance. Our case suggests that skin biopsy for more than one sample of the skin rashes is very important for the diagnosis of intravascular large B-cell lymphoma. CHOP therapy might be effective in this case because of early diagnosis by skin biopsy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

[Bisphenol.alkylphenols].

Bisphenol A and some alkylphenols such as p-nonylphenol and p-tert-octylphenol, have been noticed as endocrine disruptors, showing estrogenic activities. In this article, the knowledge of endocrine disrupting toxicities of these chemicals is reviewed. These chemicals induce uterus proliferation(in both immature and ovariectomized animals), disruption of estrus cycles, etc. in rodent females. They also induce decreased weights of testes and the accessory organs with the histological atrophy in the males. The lowest adverse effect level for these chemicals is approx. 10 mg/kg/day by oral administration except fetal exposure. Because there are some reports on extremely low dose toxicities by fetal exposure, further investigation is necessary to estimate the full-time safety level.

Animals↗
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↗
PubMed1999

Production of radioactive endovascular stents by implantation of 133Xe ions.

A coronary stent was made radioactive by implantation of 133Xe ions for the purpose of suppressing the renarrowing of the part of blood vessel in which the stent is implanted. Electrons of relatively low energies emitted in the decay of 133Xe may give an antiproliferative effect of ionizing radiation to the intimal cells within a limited range of 1 mm. A 133Xe+ beam accelerated at 40 or 60 keV was directed to several stainless steel stents mounted on a target-holder table that could revolve and move up and down to distribute the 133Xe+ ions within a stent as well as among the stents. The radioactive stents produced contained up to 100 kBq of 133Xe and were implanted into the abdominal aortas of rabbits. Neointimal thickening was analyzed by histomorphometry for samples taken 4 weeks after stent implantation. The results indicate that the radioactive stents have a potential to suppress neointimal hyperplasia in rabbits.

Angioplasty, Balloon, Coronary↗
PubMed1999

The integrity of the disulfide bond in a cyclic somatostatin analog during 99mTc complexation reactions.

Recent development of a variety of thiol-free chelating agents has facilitated the design of 99mTc-labeled somatostatin analogs suitable for receptor imaging of somatostatin-positive tumors. However, it remains ambiguous whether the disulfide bonds in cyclic peptides are stable during 99mTc complexation reactions, and contradictory results have been reported regarding the integrity of disulfide bonds in cyclic somatostatin analogs. To estimate the stability of the disulfide bond in a synthetic somatostatin analog at low peptide concentrations, [125I]I-RC-160, in which radioiodine was incorporated into the 3-Tyr residue, was synthesized and the integrity of the disulfide bond of the peptide was investigated in the presence of reducing agents such as ascorbic acid, dithionite, and stannous ions. The disulfide bond in [125I]I-RC-160 remained stable in the presence of ascorbic acid in boiling water. The disulfide bond was also stable when treated with stannous ions at concentrations sufficient to reduce 99mTc for complexation with a thiol-free chelating agent, bis(hydroxamamide) analog when the 99mTc complexation reaction was performed at room temperature. However, the disulfide bond of [125I]I-RC-160 was slightly cleaved in the presence of a small amount of stannous ions when the reaction was performed in boiling water. Treatment of [125I]I-RC-160 with dithionite in boiling water markedly reduced the disulfide bond of the parental peptide. These findings indicated that synthetic somatostatin analogs may be labeled with 99mTc with stannous ions as the reducing agent without impairing their structure after conjugation of thiol-free chelating agents that provide 99mTc chelates under mild reaction conditions.

Ascorbic Acid↗
PubMed1999

Hepatolobectomy-induced depression of hepatic circulation and metabolism in the dog is counteracted by isoflurane, but not by halothane.

BACKGROUND: The effects of isoflurane and halothane anesthesia on hepatic circulation and oxygen metabolism during hepatolobectomy were investigated in the dog, in an attempt to assess which of the anesthetics was the better one for hepatic resection. METHODS: Mongrel dogs (n=24) were divided into two groups and accordingly anesthetized with isoflurane (n=12) or halothane (n = 12). Each test anesthetic was administered in air. Electromagnetic flowmeters were used to measure hepatic arterial and portal venous blood flows 1) before the inhalation of each anesthetic (baseline); 2) 1 h inhalation of 1.5 MAC (minimum alveolar concentration) of each anesthetic; and 3) 1 h after hepatolobectomy with each anesthesia. Measurements of systemic hemodynamics, blood gas tensions, and the arterial ketone body ratio were made at the same time. RESULTS: Isoflurane maintained portal venous, hepatic arterial and total hepatic blood flows better than halothane anesthesia before and after hepatolobectomy. With halothane anesthesia, hepatolobectomy decreased prominently hepatic arterial blood flow. Hepatic arterial and mesenteric vascular resistance increased in the halothane group, but remained constant in the isoflurane group after hepatolobectomy. Hepatic oxygen delivery was significantly suppressed in the halothane group, but did not change in the isoflurane group. No significant difference was found in hepatic oxygen consumption between the two groups, but the arterial ketone body ratio decreased significantly only in the halothane group before and after hepatolobectomy. CONCLUSION: The present data indicate that isoflurane has less adverse effect than halothane anesthesia on hepatic circulation, oxygen delivery and energy charge in hepatolobectomy cases.

Analysis of Variance↗
PubMed1999

Allosteric selection of ribozymes that respond to the second messengers cGMP and cAMP.

RNA transcripts containing the hammerhead ribozyme have been engineered to self-destruct in the presence of specific nucleoside 3',5'-cyclic monophosphate compounds. These RNA molecular switches were created by a new combinatorial strategy termed 'allosteric selection,' which favors the emergence of ribozymes that rapidly self-cleave only when incubated with their corresponding effector compounds. Representative RNAs exhibit 5,000-fold activation upon cGMP or cAMP addition, display precise molecular recognition characteristics, and operate with catalytic rates that match those exhibited by unaltered ribozymes. These findings demonstrate that a vast number of ligand-responsive ribozymes with dynamic structural characteristics can be generated in a massively parallel fashion. Moreover, optimized allosteric ribozymes could serve as highly selective sensors of chemical agents or as unique genetic control elements for the programmed destruction of cellular RNAs.

Acids↗
PubMed1999

Allosteric ribozymes sensitive to the second messengers cAMP and cGMP.

We have engineered allosteric ribozymes by combining modular rational design with combinatorial strategies. This new procedure was used to create allosteric ribozymes that are activated by specific nucleoside 3',5'-cyclic monophosphates (cNMPs). A random-sequence domain was attached to stem II of hammerhead ribozymes via a communication module that serves as an interface between ribozyme and the effector binding site. Subjecting this initial random pool to in vitro selection methods produced populations that respond, or cleave, only in the presence of specific effector molecules. From generation 18, 20 and 23, cGMP, cCMP and cAMP-specific responsive ribozymes, respectively, were isolated and characterized. These methods show great promise for engineering allosteric ribozymes and for creating new ligand-specific aptamers.

Allosteric Regulation↗
PubMed1999

Bone metabolic markers in the evaluation of bone scan flare phenomenon in bone metastases of breast cancer.

Bone scan flare seriously complicates evaluations of the therapeutic response of bone metastases. The value of bone metabolic markers in monitoring the therapeutic response for bone metastases in breast cancer was assessed. Twenty-three breast cancer patients with bone metastases treated by combined chemotherapy of cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) were monitored using bone scans; a bone resorption marker, pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP); a bone formation marker, bone-specific alkaline phosphatase (BAI-p); and a tumor-specific marker (CA15-3). Bone scans were performed before and 3 or 4 months after therapy. After CAF therapy, markers were measured monthly. As a control, the markers of nine patients without bone metastases who received adjuvant CAF therapy were also measured monthly. The therapeutic effect on bone metastases was assessed after the study. Five patients had progression of disease (PD), three had no change (NC), and 15 patients had partial responses (PR). Bone scan flare-up was seen in five PR patients. In patients who received adjuvant therapy, ICTP, BAI-p, and CA15-3 did not change. ICTP increased significantly in PD patients. ICTP did not increase in either NC or PR, including bone scan flare patients. BAI-p and CA15-3 did not show any discernible pattern among PD, PR, flare, and NC patients. Thus measuring ICTP could distinguish PD from NC or PR patients' responses to CAF therapy. This was true also for patients who showed bone scan flare-up. Measuring a bone resorption marker, ICTP, allows clinicians to monitor patients' responses to CAF therapy and may prevent prolonged ineffective therapy or unnecessary changes in therapy as a result of the flare phenomenon.

Adult↗