Honeycomb structure of adatoms surrounding substituted atoms: Cu(111)-(2 x 2)-3Li.
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Journal Article↗
Biomedical subjects
S Mizuno
Publications and source records attributed to S Mizuno.
Complex surface alloy formed by Li deposition on Cu(001) determined by dynamical low-energy electron diffraction.
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Journal Article↗
Flow cytometric analysis of nuclear DNA content in oral leukoplakia: relation to clinicopathologic findings.
DNA ploidy of 50 biopsy specimens of oral leukoplakia was investigated by flow cytometry, and the results were compared with the clinicopathologic appearances. The aneuploidy rate of the leukoplakias was 17/50 (34%), and the mean DNA index (DI) of the aneuploid lesions was 1.22, with a range from 0.70 to 1.84. The incidence of the aneuploidy was significantly (P < 0.01) higher in nonhomogeneous leukoplakias (11/18) than in homogeneous lesions (6/32). The aneuploidy rate of the severely dysplastic leukoplakias (11/17) was significantly higher than those of the mildly dysplastic (4/22; P < 0.01) and the nondysplastic (2/11; P < 0.02) lesions. A significant (P < 0.01) difference in the aneuploidy rate was also observed between tongue (12/23) and gingival (2/18) leukoplakias.
Aneuploidy↗
Isolation and expression of a chicken DNA methyltransferase cDNA.
A 0.5 kb fragment of chicken DNA methyltransferase cDNA was PCR-amplified using a set of degenerate primers. A clone harboring a 5 kb insert was isolated from a cDNA library by screening with the PCR-amplified cDNA fragment as a probe. The elucidated nucleotide sequence gave a 4,614 nucleotide open reading frame, and the predicted protein was highly homologous to the mouse and human DNA methyltransferases, especially in the amino acid sequence of the catalytic domain in the carboxyl-terminal region. The cysteine-rich region and Lys-Gly repeat first found in the mouse sequence were also conserved in chicken. However, about 250 amino acid residues in the amino-terminal portion of chicken DNA methyltransferase diverged from the amino-terminus of the mouse or human sequence. Northern blot analysis showed that the message of chicken DNA methyltransferase was expressed at high levels in the testis, in the lung and in Marek's virus-transformed chicken T-lymphoma cells. Expression of the chicken DNA methyltransferase in COS1 cells demonstrated that the enzyme is a so-called maintenance-type methylase. When poly(dG-dC)-poly(dG-dC) was used as the methyl acceptor, to provide a measure of de novo methylase activity, the Km value for S-adenosyl L-methionine was about 5 microM, which was 10 times higher than that when poly(dI-dC)-poly(dI-dC) was used. The affinity of DNA methyltransferase for S-adenosyl L-methionine in catalyzing de novo-type methylation activity was lower than that in catalyzing maintenance-type activity, though it was still high enough for the enzyme to work as a de novo-type methylase under physiological conditions.
Amino Acid Sequence↗
Stimulation of phagocytosis and phagosome-lysosome fusion by glycosphingolipids from Sphingomonas paucimobilis.
Sphingomonas paucimobilis, a Gram-negative opportunistic pathogen, is actively phagocytosed by human peripheral polymorphonuclear leukocytes (PMN) in vitro. However, when live or killed cells were delipidated, the phagocytic rate was clearly decreased. Therefore, we have investigated the physiological role of membrane lipids in phagocytic processes. S. paucimobilis type strain 2395 produces four classes of acidic glycosphingolipids (GL-1, GL-2, GL-3, and GL-4) with the common components of glucuronic acid, 2-hydroxy myristic acid and d18:0 or d21:1 long-chain base. The effect of acidic glycosphingolipids on phagocytosis by PMN using killed Staphylococcus aureus cells coated with glucuronosyl ceramide (GL-1) or ceramide tetrahexoside (GL-4) was also examined. The rate of phagosome-lysosome fusion by PMN was determined by counting acridine orange-stained bacteria under a fluorescence microscope. Both phagocytosis and phagosome-lysosome fusion by PMN of glycosphingolipid-coated bacteria were stimulated markedly in a dose-dependent manner. It was noted that GL-1 or GL-4 stimulated phagosome-lysosome fusion dramatically, but synthetic lipid A did not. Superoxide anion release from PMN was enhanced significantly by the coating with synthetic lipid A at higher concentration, but only slightly with GL-1 or GL-4. Glucuronic acid was an inhibitor of phagocytosis of GL-1-coated S. aureus by PMN. The effect of acidic glycosphingolipids obtained from mammalian tissue on phagocytosis was also compared with that of bacterial glycosphingolipids. Ganglioside GM3 and sulfatide showed a marked stimulative activity for phagocytosis by PMN, while the neutral glycosphingolipids did not. Thus, bacterial acidic glycosphingolipid and mammalian acidic glycosphingolipid promote phagocytosis and phagosome-lysosome fusion by PMN.
Glycosphingolipids↗
A pharmacokinetic and pharmacodynamic analysis of CPT-11 and its active metabolite SN-38.
In the present study, an attempt was made to determine the precise pharmacokinetics of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). The relationship between pharmacokinetic parameters and pharmacodynamic effects was also investigated to elucidate the cause of interpatient variation in side effects. Thirty-six patients entered the study. CPT-11, 100 mg/m2, was administered by IV infusion over 90 min weekly for four consecutive weeks. The major dose-limiting toxicities were leukopenia and diarrhea. There was a positive correlation between the area under the concentration-time curve (AUC) of CPT-11 and percent decrease of WBC (r = 0.559). On the other hand, episodes of diarrhea had a better correlation with the AUC of SN-38 (r = 0.606) than that of CPT-11 (r = 0.408). Multivariate analysis revealed that the AUC of SN-38, AUC of CPT-11 and indocyanine green retention test were significant variables for the incidence of diarrhea and that both performance status and AUC of CPT-11 were significant variables for percent decrease of WBC. The large interpatient variability of the degree of leukopenia and diarrhea is due to a great plasma pharmacokinetic variation in CPT-11 or SN-38. The AUCs of CPT-11 and SN-38 obtained from the first administration of CPT-11 correlate with toxicities, but it is impossible to predict severe side effects before the administration of CPT-11 at the present time.
Adult↗
A limited sampling model for estimating pharmacokinetics of CPT-11 and its metabolite SN-38.
The objective of this study was to develop a limited sampling model (LSM) to estimate the area under the curve (AUC) of 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and that of 7-ethyl-10-hydroxycamptothecin (SN-38) as predictive pharmacokinetic variables for leukopenia and episodes of diarrhea induced by CPT-11 administration. The model was developed with a training set consisting of pharmacokinetic studies in 36 patients who received a 90-min i.v. infusion of CPT-11 at a dose of 100 mg/m2. A multiple regression analysis of CPT-11 or SN-38 concentrations observed at each time point in the training set was used to predict the AUC of CPT-11 or SN-38. The final sampling models using only two time points were: AUCCPT-11 = 3.7891*C2.5 + 14.0479*C13.5 + 1.5463 AUCSN-38 = 0.5319*C2.5 + 19.1468*C13.5 + 72.7349 where C2.5 and C13.5 are the plasma concentration of CPT-11 (micrograms/ml) or SN-38 (ng/ml) at 2.5 and 13.5 h after the initiation of CPT-11 infusion, respectively. The models were validated prospectively on a separate test data set of 12 patients receiving the same dose of CPT-11 investigated in a previous study. Validation of the final LSM on the test data set gave values of root mean square error (RMSE) of 12.72% and 5.97% for the AUC of CPT-11 and that of SN-38, respectively. The model can be used to monitor the AUCs of both CPT-11 and SN-38 for the early prediction of toxicities and to establish a pharmacokinetically based dose modification strategy for safe administration of CPT-11.
Adult↗
Quantitative analysis of AML1/ETO transcripts in peripheral blood stem cell harvests from patients with t(8;21) acute myelogenous leukaemia.
Peripheral blood stem cells (PBSC) have been used increasingly for haemopoietic reconstitution after marrow-ablative chemotherapy in patients with acute leukaemia because of the possibility that there is a lower risk of leukaemic contamination. We have developed a titration assay using a competitive reverse transcriptase polymerase chain reaction (RT-PCR) which is able to estimate the number of AML1/ETO transcripts so that minimal residual disease (MRD) can be monitored quantitatively in patients with t(8;21) acute myelogenous leukaemia (AML). Using a qualitative RT-PCR method, AML1/ETO transcripts could be detected in all samples from 15 first PBSC harvests and 11 second PBSC harvests obtained from 15 patients with t(8;21) AML. With our competitive RT-PCR assay, the number of AML1/ETO transcripts was found to be lower in the second PBSC harvest than that in the first in every individual. Furthermore, MRD in PBSC harvests was less than that in the corresponding bone marrow obtained on the day of PBSC collection in the individual patients studied. In 10 patients who received autologous blood stem cell transplantation (ABSCT), we could not find a relationship between the number of AML1/ETO transcripts in the infused PBSC harvests and the clinical outcome after ABSCT. The present study clearly indicates that although PBSC harvests collected after consolidation chemotherapy are contaminated by leukaemic cells, the degree of leukaemic contamination may decrease as chemotherapy is repeated. The mobilization of PBSC by repeated chemotherapy may provide an advantageous source of haemopoietic stem cells for ABSCT.
Adolescent↗
Characterization of blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia.
We investigated the biological characteristics of 'eosinophilic' leukaemic blasts from a patient with eosinophilic blast crisis of chronic myelogenous leukaemia (CML). Southern blot analysis of the bcr gene demonstrated the identical single rearranged band in both the leukaemic blasts and mature eosinophils. IL-3, IL-5 and GM-CSF significantly enhanced proliferation and differentiation of these leukaemic blasts, and only eosinophils were generated from in vitro cultures. Those eosinophils expressed the B3A2 chimaeric messenger RNA seen in the leukaemic blasts. These observations indicate that eosinophil progenitors may be involved in the development of eosinophilic blast crisis of CML and that IL-3, IL-5 and GM-CSF act on the leukaemic eosinophil progenitors.
Blast Crisis↗
[Good response to ganciclovir in a patient of cytomegalovirus (CMV) interstitial pneumonitis and gastric ulcer following allogeneic bone marrow transplantation for acute lymphoblastic leukemia].
This 35-year-old housewife was initially treated with vincristine, prednisolone and L-asparaginase for acute lymphoblastic leukemia (ALL, L1 by FAB classification) in 1988 and entered into complete remission. Ten months later she underwent bone marrow transplantation (BMT) from her HLA-identical and MLC-negative sister. The conditioning regimens consisted of busulfan 4 mg/kg/day for 4 days orally and cyclophosphamide 60 mg/kg/day for 2 days intravenously followed by cyclosporine and prednisolone for graft-versus-host disease prophylaxis. Fifty days after BMT, she suffered interstitial pneumonitis and a gastric ulcer, and was treated with a high dose of methylprednisolone and cimetidine. She experienced transient improvement, but soon cough, dyspnea and epigastralgia became worse. The specimens obtained by transbronchial alveolar lavage (BAL) and endoscopic gastric biopsy showed many giant cells containing inclusion bodies which were identified as cytomegalovirus (CMV). This time ganciclovir was started in addition to prednisolone. Then she gradually improved and after repeated BAL and the gastric biopsy after treatment showed no inclusion body in the specimen. Although leukocytopenia was significant for this patient, ganciclovir is considered to be useful for controlling CMV infection in both the lungs and stomach.
Adult↗
[Clinical use of EVAR and OVAR by the dumped rotation test--comparison of normal volunteers and patients with unilateral vestibular nerve section].
Horizontal eye movements in response to either earth vertical axis rotation (EVAR) or off vertical axis rotation (OVAR) by a 10 degree tilted axis were recorded in six normal subjects and three patients with unilateral vestibular nerve section. Both trials consisted of acceleration at approximately 400 deg/sec2 until an angular velocity of 180 deg/sec was reached followed by deceleration at -4 deg/sec2 until rotation ceased. This is the so-called dumped rotation procedure. Total numbers of nystagmic beats and the duration of perrotatory nystagmus in these two different trials were compared. The results were as follows: 1) Total numbers of nystagmic beats in OVAR were significantly larger than in EVAR. 2) The duration of perrotatory nystagmus in OVAR was significantly longer than in EVAR. Only the horizontal semicircular canals were stimulated by angular acceleration in EVAR, whereas both otolith organs and semicircular canals were stimulated on changing the position of the head around the direction of the gravity in OVAR.
Acceleration↗
PCR inhibition assay for DNA-targeted antibiotics.
DNA amplification by polymerase chain reaction (PCR) should be inhibited if the target for amplification region in the template DNA is nicked or cut. Based on this premise, we established a sensitive and differential assay using PCR to detect antibiotics that act on DNA. After template lambda DNA (10 pg) was incubated with antibiotics (10 approximately 20 ng) at 37 degrees C for 30 minutes in a 5 microliters reaction volume, a PCR assay (10 microliters reaction volume; 25 approximately 30 cycles) was performed under the conditions we modified, resulting in amplification of a 500 bp fragment of lambda DNA which was monitored by agarose gel electrophoresis. Among the several antibiotics examined, the anthracyclines, bleomycin, D-cycloserine and mitomycin C clearly inhibited the PCR amplification reaction, whereas actinomycin D and ofloxacin did not. Preincubation of template DNA in the presence of Fe++ was necessary for bleomycin and cycloserine to exhibit marked inhibition of PCR. Mitomycin C exhibited the inhibition in the presence of DTT and Cu+. By contrast, non-DNA-acting antibiotics (200 ng) such as aminoglycosides, beta-lactams, and macrolides showed no inhibition. The PCR-amplified fragment from lambda DNA was not degraded by incubation with the antibiotics (20 ng) that inhibited PCR. Furthermore, ethylacetate extracts of the cultured broths of actinomycetes proved to be suitable as samples for this PCR inhibition assay.
Actinomycetales↗
[Primary intracranial malignant epidermoid--case report].
Intracranial malignant epidermoid is uncommon. We report a case of a 74-year-old woman with a primary intracranial malignant epidermoid in the parapontine region. The tumor was visualized as two components (a low-density benign prepontine lesion and a malignant enhanced cerebellopontine angle lesion) on CT scan. On MRI, the benign portion demonstrated low-signal intensity on T1 weighted images and markedly increased heterogeneous signal intensity on T2 weighted images, while the malignant portion showed iso-signal intensity on T1 weighted images that was markedly enhanced and heterogeneous signal intensity on T2 weighted images. Lack of contrast enhancement is a typical finding in benign epidermoid, although rim enhancement has been described in a few cases. In our patient, the contrast enhancement on CT scan in the otherwise typical epidermoid cyst suggested malignant degeneration. Using MR imaging, we could distinguish malignant epidermoid from benign epidermoid cyst more precisely.
Aged↗
Reevaluation of prognostic factors in gastric leiomyosarcoma.
OBJECTIVES: The aim of our study was to reevaluate the prognostic factors in gastric leiomyosarcomas, particularly those under 6 cm, which, because of improved diagnostic techniques, make up a large proportion of this series, in contrast to previously published works. METHODS: The clinicopathological features in 83 patients with gastric leiomyosarcoma were reviewed. Cox's proportional hazards regression analysis was used to determine the prognostic factors. RESULTS: Sixty of 84 leiomyosarcomas (71.4%) were less than 6 cm in diameter. In univariate analysis, the following factors were considered to be unfavorable, with statistical significances: 1) presence of distant metastasis and/or direct invasion of adjacent structures at diagnosis (hazard ratio 36.60), 2) > or = 4 mitoses per 20 high-power fields (25.39), 3) severe nuclear atypia (16.74); 4) presence of ulceration of overlying gastric mucosa (12.57), and 5) diameter > or = 6 cm (5.57). Among these factors, mucosal ulceration has been identified as a new factor associated with poor prognosis. Histologically, the tumors with ulceration showed more severe nuclear atypia (p < 0.05), necrosis (p < 0.01), and a higher incidence of mitosis (p < 0.01), compared with tumors without ulceration. In multivariate analysis, factors 1, 2, and 3 were statistically significant, although neither size nor ulceration was significant. CONCLUSIONS: The presence of distant metastasis and/or direct invasion, high mitotic rate, and severe nuclear atypia were confirmed to be unfavorable prognostic indicators. Mucosal ulceration, indicating high proliferative activity of the tumor, even if small, suggests a poor prognosis, although it was not significant in multivariate analysis.
Combined Modality Therapy↗
[The progress of autologous peripheral blood stem cell transplantation].
It has recently become known that sufficient numbers of multi-potent stem cells transiently appear in the peripheral blood at the time of recovery from myelosuppression after chemotherapy for collection for later transfusion (autologous peripheral blood stem cell transplantation; ABSCT). It is also known that cytokines such as G-CSF or GM-CSF enhance the mobilization of stem cells in peripheral blood. It is, therefore, easy to collect a large number of progenitor cells using the apheresis technique. We have also succeeded in developing an easy preservation method using DMSO-HES-ALBUMIN as a cryoprotective agent for simple storage in a -80 degrees C refrigerator. Furthermore, the development of measurement of CD34 positive cells become easy to estimate the contents of progenitor cells in harvested peripheral mononuclear cells. These techniques contribute to the safe and reliable practice of ABSCT. There are high expectations for ABSCT as a new technique in the cure of patients with such diseases as hematological malignancy and chemotherapy sensitive solid tumor, as it makes possible the administration of super-high dose anti-cancer drugs which cause marrow ablation.
Hematopoietic Stem Cell Transplantation↗
Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese.
To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.
Adolescent↗
Genotyping analysis of HLA-class II and III genes in unrelated bone marrow transplantation among Japanese. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank.
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Adolescent↗
Histochemical studies of the separation of the lens vesicle in the mouse.
Histochemical studies were carried out in the mouse on the changes and distribution patterns of glycosaminoglycan molecular species during the separation of the lens vesicle. To obtain embryos, pregnant mice of the Jcl:ICR strain were sacrificed on day 10.5 or 11 of pregnancy. Serial frontal sections were strained with hematoxylin-eosin and sensitized high iron diamine. To identify glycosaminoglycan molecular species in tissues, an enzyme digestion (double digestion with chondroitinase B and testicular hyaluronidase) and a chemical modification (nitrous acid treatment) were performed in combination with the sensitized high iron diamine method. Before separation of the lens vesicle, chondroitin sulfate A/C and B were found in the basement membrane of the future corneal epithelium and intercellular matrices between the future corneal epithelium and lens vesicle, and chondroitin sulfate A/C was identified in the lens capsule. After separation of the lens vesicle, heparan sulfate emerged in the basement membrane of the future corneal epithelium and intercellular matrices between the future corneal epithelium and lens vesicle. These results indicate that the changes and distribution pattern of glycosaminoglycan molecular species play an important role during the separation of the lens vesicle.
Animals↗