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Biomedical subjects

K Kuramoto

Publications and source records attributed to K Kuramoto.

At least 19 recordsLinked to original sources

C1s and O1s photoelectron satellite spectra of CO with symmetry-dependent vibrational excitations.

The photoelectron shake-up satellite spectra that accompany the C1s and O1s main lines of carbon monoxide have been studied by a combination of high-resolution x-ray photoelectron spectroscopy and accurate ab initio calculations. The symmetry-adapted cluster-expansion configuration-interaction general-R method satisfactorily reproduces the satellite spectra over a wide energy region, and the quantitative assignments are proposed for the 16 and 12 satellite bands for C1s and O1s spectra, respectively. Satellite peaks above the pi(-1)pi(*) transitions are mainly assigned to the Rydberg excitations accompanying the inner-shell ionization. Many shake-up states, which interact strongly with three-electron processes such as pi(-2)pi(*2) and n(-2)pi(*2), are calculated in the low-energy region, while the continuous Rydberg excitations are obtained with small intensities in the higher-energy region. The vibrational structures of low-lying shake-up states have been examined for both C1s and O1s ionizations. The vibrational structures appear in the low-lying C1s satellite states, and the symmetry-dependent angular distributions for the satellite emission have enabled the Sigma and Pi symmetries to be resolved. On the other hand, the potential curves of the low-lying O1s shake-up states are predicted to be weakly bound or repulsive.

Journal Article↗

Synthesis of bioactive PMMA bone cement via modification with methacryloxypropyltri-methoxysilane and calcium acetate.

Bone cement consisting of polymethylmethacrylate (PMMA) powder and methylmethacrylate (MMA) liquid is clinically used for fixation of implants such as artificial hip joints. However, it does not show bone-bonding ability, i.e., bioactivity. The lack of bioactivity would be one of factors which cause loosening between the cement and the implant. The present authors recently showed the potential of bioactive PMMA-based bone cement through modification with gamma-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. In this study, the effects of the kinds of PMMA powder on setting time, apatite formation and compressive strength were investigated in a simulated body fluid (Kokubo solution). The cement modified with calcium acetate calcined at 220 degrees C could set within 15 min when the PMMA powder had an average molecular weight of 100,000 or less. The addition of calcium acetate calcined at 120 degrees C in the PMMA powder required a much longer period for setting. The modified cements formed an apatite layer after soaking in the Kokubo solution within 1 day for cement starting from PMMA powder with a molecular weight of 100,000 or less. Compressive strengths of the modified cements were more than 70 MPa for cements starting from 100,000 and 56,000 in molecular weight. After soaking in Kokubo solution for 7 days, the modified cement consisting of PMMA powder of 100,000 in molecular weight showed a smaller decrease in compressive strength than that consisting of 56,000 in molecular weight. These results indicate that bioactive PMMA cement can be produced with appropriate setting time and mechanical strength when PMMA powders with a suitable molecular weight are used. Such a type of design of bioactive PMMA bone cement leads to a novel development of bioactive material for bone substitutes.

Acetates↗

Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells.

Myelodysplastic syndrome (MDS) is a clonal disorder of hematopoietic stem cells. To investigate whether chromosomal instability and/or DNA repair defects are involved in the development of MDS, we measured the micronucleus (MN) frequency in peripheral blood lymphocytes exposed to various doses of X-rays, using a cytokinesis-block micronucleus assay. The spontaneous MN frequencies in RAEB and RAEB-T patients were significantly higher than those in normal individuals (P = 0.0224, P = 0.008, respectively). Also, the X-ray-induced MN frequencies in RA/RARS, RAEB, and RAEB-T patients were significantly higher than those in normal individuals (P = 0.007, P = 0.003, P = 0.003, respectively, at 2 Gy). In order to elucidate the cause of unusual radiosensitivity, we measured the expression levels of nucleotide excision repair (NER) genes in peripheral blood mononuclear cells using a RT-PCR method. Reduction of NER gene expression was found in only one of 10 patients with low risk MDS, but in four of 11 patients with high risk MDS. Our data suggest that chromosomal instability and DNA repair defects may be involved in the pathophysiology of disease progression of MDS.

Adult↗

Tolerability and safety of a calcium channel blocker in comparison with a diuretic in the treatment of elderly patients with hypertension: secondary analysis of the NICS-EH.

A randomized prospective controlled study, the National Interventional Cooperative Study in Elderly Hypertensives (NICS-EH), previously demonstrated that the preventive effect of the long-acting calcium channel blocker nicardipine on the cardiovascular endpoint was similar to that of the diuretic, trichlormethiazide. The present report is a sub-analysis in which we compare the tolerability and safety of the calcium channel blocker with that of a diuretic in the long-term treatment of elderly hypertensives. A total of 429 elderly patients with hypertension were assigned to the nicardipine group or the diuretic group by the double-dummy method and were followed up for 5 years. Two hundred four patients in the nicardipine group and 210 patients in the diuretic group were analyzed. The incidences of fatal and nonfatal cardiovascular (CV) events in the two groups were comparable, and there was no significant difference in the cumulative event-free rate. However, the total incidence of adverse reactions, including non-CV events and unfavorable BP changes, was 31 cases (15.2%) in the nicardipine group, which was significantly lower than the 47 cases (22.4%) in the diuretic group (log-rank: p=0.026, G. Wilcoxon: p=0.01). The total number of medical endpoints, including CV events, the withdrawal of the patient from the study, was 52 (25.5%) in the nicardipine group, which was significantly lower than the 65 (31.0%) in the diuretic group (log-rank: p=0.078, G. Wilcoxon: p=0.044). It was concluded that sustained-release nicardipine is better tolerated, as it exhibits a lower incidence of medical-related withdrawals such as adverse drug reactions, non-cardiovascular events and unfavorable BP responses during the treatment.

Aged↗

ZK7, a novel zinc finger gene, is induced by vascular endothelial growth factor and inhibits apoptotic death in hematopoietic cells.

Vascular endothelial growth factor (VEGF) inhibits radiation-induced apoptosis in the leukemia cell line, CMK86 (O. Katoh et al., Cancer Res., 55: 5687-5692, 1995). To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we attempted to identify a transcription factor involved in the cellular response to VEGF stimulation. We cloned the cDNA of a novel Kruppel-type zinc finger (ZNF) gene, ZK7, from a cDNA library constructed from the human leukemia cell line CMK86 after incubation with VEGF. This cDNA encoded a protein of 289 amino acids, which contained a Kruppel-associated box A-box domain at the NH2 terminus and seven ZNF motifs at the COOH terminus. These ZNF motifs were identical to those of HZF16 (M. Saleh et al., Am. J. Hum. Genet., 52: 192-203, 1993). ZK7 and HZF16 genes appear to be the splice variants transcribed from the same gene. Northern blotting and quantitative reverse transcription-PCR analysis revealed that expression of ZK7 mRNA in CMK86 cells and human hematopoietic progenitor cells was increased after VEGF stimulation, whereas that of HZF16 mRNA remained unchanged. To examine the function of ZK7 protein, we generated clones of a human monocytoid leukemia cell line, U937, which were stably transfected with ZK7 or HZF16 cDNA. Importantly, ZK7-overexpressing cells had lower sensitivity to ionizing radiation and the chemotherapeutic agent etoposide than U937 parent cells or HZF16-overexpressing cells. Therefore, ZK7 protein may be involved in the inhibitory effect of VEGF on apoptotic cell death in human hematopoietic cells.

Amino Acid Sequence↗

Effect of long-term treatment with antihypertensive drugs on quality of life of elderly patients with hypertension: a double-blind comparative study between a calcium antagonist and a diuretic. NICS-EH Study Group. National Intervention Cooperative Study in Elderly Hypertensives.

We investigated the effect of long-term treatment with a calcium antagonist (nicardipine hydrochloride retard tablet) and a diuretic (trichlormethiazide) on quality of life (QOL) in elderly hypertensives in a multicenter, randomized, double-blind, comparative study (National Intervention Cooperative Study in Elderly Hypertensives Study Group). The percentage of patients who experienced side effects was 17.2% in the nicardipine group and 18.1% in the trichlormethiazide group and 2.9% and 4.3% of participants, respectively, withdrew due to those side effects. These results suggested that nicardipine was tolerated slightly better than trichlormethiazide. There were no significant differences between the two groups in terms of total QOL score or in degree of change (delta score) before and after calcium antagonist or diuretic administration. Lower score was seen in 3 categories (general symptoms, sleep scale, and sexual function) in the trichlormethiazide group (p< 0.05) and in one category (cognitive function) in the nicardipine group, but there was no significant difference in delta score in any of the individual items. In conclusion, the two anti-hypertensive agents had nearly equivalent effects on QOL in the long-term treatment of hypertension in the elderly and that neither resulted in a deterioration in QOL.

Aged↗

Establishment and characteristics of four sub-strains of F344 rats reared on various low protein and low energy diets.

Four sub-strains, reared by sib-mating and having for their origin the F344/DuCrj strain of rats, were established by feeding with different levels of low protein and low energy diets, and their characteristics investigated. The amounts of crude protein (CP) and digestible energy (DE) in the four diets were 17.6%-3.0 kcal, 10.5%-2.5 kcal, 8.4%-2.0 kcal, and 10.5%-2.5 kcal, respectively, and the four sub-strains established here were provisionally designated as F344/Tig1, F344/Tig2, F344/Tig3 and F344/Tig4, respectively. Intakes of nitrogen-corrected metabolizable energy (MEn) did not differ, and a large intake of digestible crude protein (DCP) was observed in F344/Tig1 rats. The body weight of rats provided with lower-nutrient diets showed a tendency to decrease until the F2 generation, but no change among the generations was seen subsequently, and the same compiled differences in protein content were maintained. Similar transitions were observed in the lifetime rearing test. Though F344/Tig3 rats, which were reared on minimum nutrients, showed a tendency to delayed puberty, we were easily able to breed four pairs in every generation using procedures similar to those used for other strains of rats. There were no differences among the F344/Tig1 to -3 strains of rats in body length, digestive tract length, or organ weight per body weight, and all the rats had a normal range of biochemical values. But the F344/Tig4 showed a high glutamic-oxaloacetic transaminase (GOT), and a tendency to decreased liver function and a shorter lifespan. These sub-strains of F344 rats clarified differences in fatty acid compositions, such as docosahexaenoic acid (DHA) in serum, liver and the brain. The rats were intended to be useful animal models for the study of nutritional environments and their influence on the memory and learning.

Animal Feed↗

Transcatheter embolization of mycotic aneurysm of the subclavian artery with metallic coils.

Mycotic aneurysms of the subclavian artery are rare. This report describes an experience of 2 rare cases in which transcatheter embolization with metallic coils was performed for the management of these lesions alternative to surgery. Two patients who had been treated with chemotherapy for malignant neoplasms were diagnosed as having mycotic aneurysms of the left subclavian artery. The causes of these lesions were presumed to be the invasion of the arterial wall by the pulmonary abscess in case 1, and wound infection after placement of the reservoir for intraarterial chemotherapy in case 2. In both cases, proximal and distal sites of the aneurysm were embolized with metallic coils. In case 1, the vertebral artery was also embolized with Guglielmi detachable coils to avoid retrograde blood flow. Both aneurysms were completely occluded by a single embolization. In case 1, although weakness and paresthesia of the left hand remained, lethal hemoptysis due to aneurysmal fistulization to the lung parenchyma ceased. In case 2, no neurological deficit except for mild paresthesia in the left thumb had been observed. Both patients died of primary disease 10 and 5 months after the procedure. Transcatheter embolization is technically feasible and effective enough to treat the mycotic aneurysm of the subclavian artery even in the situation in which the surgical option seems to be difficult or risky.

Aneurysm, Infected↗

[MALT lymphoma producing IgG-kappa type M-protein].

A 72-year-old woman, who has been administered prednisolone and azathioprine with diagnoses of idiopathic thrombocytopenic purpura (ITP) and autoimmune hepatitis (AIH), underwent a complete medical examination because of monoclonal gammopathy (IgG-kappa). Tumors were found in the ileum and descending colon. Pathological examination of biopsy specimens suggested a diagnosis of marginal zone B-cell lymphoma of the MALT type with a high-grade component. Flow cytometric analysis by two-color staining revealed that the neoplastic B cells expressed CD38, CD19, IgG and kappa, but not CD5 or CD10. There were no abnormal plasma cells in bone marrow smears. The patient achieved complete remission after receiving three cycles of THP-COP chemotherapy, which resulted in a decrease of the IgG level to within the normal range. These findings indicated that monoclonal IgG-kappa might be produced by lymphoma cells. However, the relationship of the immunosuppressive agents to the pathogenesis of the MALT lymphoma remains to be clarified.

Aged↗

Gastric tumor induction by 1,2-dimethylhydrazine in Wistar rats with intestinal metaplasia caused by X-irradiation.

Five-week-old male Wistar rats were X-irradiated with a total of 20 Gy in 2 equal fractions at a 3-day interval. 1,2-Dimethylhydrazine (DMH) solution was injected i.m. into the back musculature at a dose of 20 mg/kg body weight weekly for 10 weeks, beginning 20 weeks after the final irradiation. Twelve months after the initial carcinogen treatment, tumors in the fundus of the glandular stomach were observed in 5 of 23 animals receiving both X-irradiation and DMH treatment. No tumors of the glandular stomach were observed in the DMH and X-ray alone or nontreatment groups. It is concluded that the presence of intestinal metaplasia may increase sensitivity to the induction of gastric tumors by carcinogens like DMH.

1,2-Dimethylhydrazine↗

Vascular endothelial growth factor inhibits apoptotic death in hematopoietic cells after exposure to chemotherapeutic drugs by inducing MCL1 acting as an antiapoptotic factor.

We reported previously that vascular endothelial growth factor (VEGF) inhibits the apoptotic death of hematopoietic cells that is induced by exposure to ionizing radiation (O. Katoh et al., Cancer Res., 55: 5687-5692, 1995). In this study, we show that VEGF also inhibits apoptotic cell death that is induced by exposure to the chemotherapeutic drugs etoposide and doxorubicin. To elucidate the molecular mechanisms underlying this inhibitory effect of VEGF, we examined expression levels of BCL2 family proteins in CMK86, a human leukemia cell line, after treatment with VEGF. Northern blotting and immunoblotting analyses revealed that the expression level of MCL1, a member of the BCL2 family, was increased by VEGF. Moreover, to examine the effects of MCL1 on apoptotic cell death induced by exposure to etoposide, we generated a clonal U937 myeloid leukemia cell line transfected with vectors that promoted the constitutive expression of MCL1. MCL1 decreased the caspase 3 activity induced by exposure to etoposide and increased the viability of the transfected cells after etoposide exposure. Therefore, MCL1 may be involved in the inhibitory effect of VEGF on apoptotic cell death.

Antineoplastic Agents↗

The Krüppel-type zinc finger family gene, HKR1, is induced in lung cancer by exposure to platinum drugs.

To investigate the molecular mechanism associated with the signaling pathway of platinum drug administration, we focused on the C2H2-type zinc finger (ZNF) transcription factor gene family. Here we show cloning of a Krüppel-type ZNF gene, HKR1, which contains Krüppel-associated box (KRAB) domain and ZNF motifs. We found that mRNA expression of the HKR1 gene was induced in lung-cancer cell lines by exposure to cisplatin using Northern blot analysis. Moreover, we also found that HKR1 mRNA expression levels in lung cancers were higher than those in normal lung tissues, and that high expression levels in lung cancers were associated with antemortem platinum drug administration. These results suggest that HKR1 may be associated with the regulation of a signaling pathway involved in the progression of lung cancer or the acquisition of resistance to platinum drugs.

Adenocarcinoma↗

Cell kinetics of hemopoietic colony-forming units in spleen (CFU-S) in young and old mice.

The growth potential of the hemopoietic progenitor cells from young and old mice is similar. Previous studies of their cell-kinetics showed no significant differences between them when measured by the incorporation of tritiated thymidine ([3H]TdR). A different approach for exploring stem-cell kinetics in aged animals is provided by another method; the incorporation of bromodeoxyuridine (BrdUrd) during DNA synthesis followed by exposure to near-ultraviolet light (near-UV) kills BrdUrd labelled cells in DNA-synthesis (S-phase). This BrdUrd-near UV cytocide (BUUV) reveals the size of cycling fractions at the level of hemopoietic progenitor cells; it also demonstrates the velocity of the cells entering S-phase when cells are labeled by a continuous infusion of BrdUrd by an osmotic pump, followed by an appropriate colony-assay for each progenitor cell. We compared the cell kinetics of young and old hemopoietic progenitor cells (CFU-S) by this approach. Osmotic pumps were implanted subcutaneously in the backs of young (2 months) and old (22 months) male C57BL/6CrSlc mice for 2, 4, 8, 12, and 16 days to continuously infuse BrdUrd at a flow-rate of 1 mg/h per kg. Cells were harvested from femoral marrow of the infused mice, plated in non-coated bacterial plates, and exposed to a single dose of near-UV at 4000 J/m2. After BUUV cytocide, bone-marrow cells were assayed for 8- and 13-day CFU-S colonies. In the 8-day colonies, the cytocide fraction of CFU-S from young mice increased rapidly, whereas the fraction from old mice showed flatter curves. Both curves reached a plateau at 52.6% for young, and 43.9% for old mice, and then converged 4 days after labeling. In the 13-day colonies, the curve for the aged was much flatter than that for the young; however, the plateaus in both young and old are similar, but at much lower values than earlier, i.e. 24.5% and 16.0%, respectively. The size of the cycling fraction of progenitor cells was close in the two groups during the steady-state cell-cycle. However, the velocity of the cell cycle at a progenitor level was very different, old mice being much slower. Further, within the progenitors, the cell cycle was much slower in the primitive ones and became faster when the stem cells differentiated into mature progenitor cells.

Aging↗

Hepatitis C virus infection in acquired aplastic anemia.

Hepatitis-associated aplastic anemia (HAAA) is an uncommon disorder that usually is not due to hepatitis A or B virus infection. Hepatitis C virus (HCV) seropositivity is infrequently observed in aplastic anemia (AA) patients who have not been extensively transfused. However, HCV seropositivity may not be detected until several weeks or months after viral infection and AA patients may exhibit defective humoral immunity. Therefore, we evaluated sera from AA patients for the presence of HCV viremia using a reverse transcriptase polymerase chain reaction (RT-PCR) based assay and several serologic assays for HCV antibodies. Serum samples from 90 AA patients who presented to the UCLA Medical Center between March 1984 and February 1990 were analyzed. Overall, 17 patients were found to have HCV viremia by RT-PCR assay, of whom 14 had a positive second-generation HCV enzyme immunoassay (EIA-2) and only 6 were EIA-1 reactive. The frequency of HCV viremia increased with the duration of time between diagnosis and sample procurement, and the number of blood products transfused prior to sampling (P = 0.026). No patient who received fewer than 20 U of blood products or who was sampled less than 20 days after diagnosis had a positive HCV RT-PCR result. Of four patients with hepatitis-associated AA (HAAA), one who was sampled 23 days after diagnosis had hepatitis C viremia and a reactive EIA-2 assay. Therefore, the high frequency of HCV viremia in this patient population is most likely due to transfusion with contaminated blood products prior to the introduction of routine blood donor screening for HCV.

Anemia, Aplastic↗

The effects of dilution on the outcome of pooled plasma testing with HIV type 1 (HIV-1) RNA genome amplification as compared to the outcome of individual-unit testing with other HIV-1 markers.

BACKGROUND: Proposed testing of large plasma pools with genome amplification technology (GAT) for detection of transfusion-transmissible viruses may have unanticipated complications not associated with individual unit testing. One such potential complication, the effect of dilution resulting from pool formation, was the subject of the present study. STUDY DESIGN AND METHODS: Specimens from three plasma donor HIV type 1 (HIV-1) seroconversion panels were tested with a quantitative HIV-1 RNA GAT assay (lower detection limit, 400 copies). GAT results were compared to HIV-1 p24 antigen and anti-HIV-1/2 enzyme immunoassay results. Effects of dilution on the detection of GAT-positive panel specimens were assessed by terminal dilution with pooled volunteer-donor EDTA plasma samples. RESULTS: Low HIV-1 RNA copy numbers (755 and 890 copies/0.1-mL input) that were detectable in two individual plasma specimens before HIV-1 p24 antigen were subsequently undetectable by GAT upon dilution with an equal volume of nonreactive plasma from a single donor. HIV-1 RNA at higher copy numbers (15,500 copies/0.1-mL input) in an HIV-1 p24 antigen-reactive and anti-HIV-1/2-nonreactive specimen was undetectable when diluted to 1-in-50 (1-in-50). Terminal dilution of seven HIV-1 RNA-containing plasma panel specimens indicated a proportional loss of HIV-1 RNA detectability with increasing dilution. CONCLUSION: GAT for detection of HIV-1 RNA in individual specimens was more sensitive than other HIV markers. For pooled plasma testing, GAT-independent constraints, such as effects of dilution, may preclude the use of GAT detection as a replacement for individual unit testing with HIV serologic assays.

Gene Amplification↗

An approach for acute disruption of large arteries in patients with advanced cervical cancer: endoluminal balloon occlusion technique.

OBJECTIVE: To test the feasibility of an intraluminal balloon occlusion technique for the control of sudden arterial disruption from cervical branches in patients with advanced malignancy. BACKGROUND: A sudden disruption of large cervical arteries is a devastating complication of advanced cervical malignancy and local infection. METHODS: Three patients with this complication underwent endoluminal balloon occlusion before surgical management. A double-lumen balloon catheter was introduced from the femoral artery to the bleeding point. Angiographic examination of the intracranial cross-filling could be performed by the injection of contrast medium from the opposite carotid artery, and consciousness levels could be directly confirmed under unilateral carotid occlusion. RESULTS: Resection of the carotid or innominate artery was safely performed in all the patients. No neurologic complications occurred. Bleeding did not recur during follow-up (range 5-32 months). CONCLUSIONS: This experience, although limited, suggests that surgical intervention to control cervical arterial bleeding with intraluminal balloon occlusion prevents excessive bleeding, decreases the risk of damage to the central nervous system, and improves the outcome in these critically ill patients.

Acute Disease↗