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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 37 records · Page 2Linked to original sources
PubMed2004

Induction of differentiation of human myeloid leukemia cells by jasmonates, plant hormones.

Some regulators of plant growth and differentiation have been shown to induce the differentiation of several human myeloid leukemia cells, and might be effective as differentiation inducers to control acute myelogenous leukemia cells. In this study, the growth-inhibiting and differentiation-inducing effects of jasmonates on human myeloid leukemia cells were examined. Several myeloid leukemia cells were cultured with methyl jasmonate (MJ) and its derivatives. Cell differentiation was determined by nitroblue tetrazolium-reducing activity, morphological changes, alpha-naphthyl acetate esterase activity and expression of differentiation-associated surface antigens. MJ induced both monocytic and granulocytic differentiation of HL-60 cells. MJ activated mitogen-activated protein kinase (MAPK) in the cells before causing myelomonocytic differentiation. MAPK activation was necessary for MJ-induced differentiation, since PD98059, an inhibitor of MAPK kinase, suppressed the differentiation induced by MJ. MJ also induced the differentiation of other human leukemia cell lines. Introduction of a double bond at the 4,5-position greatly enhanced the differentiation-inducing activity of MJ. MJ and its derivatives potently induce the differentiation of some myelomonocytic leukemia cells. One novel derivative is a particularly promising therapeutic agent for the treatment of leukemia.

Cell Differentiation↗
PubMed2004

The effects of a herbal medicine (Mao-to) in patients with chronic hepatitis C after injection of IFN-beta.

We found that a herbal medicine (Mao-to) relieves the side effects of interferon (IFN)-beta and the combination therapy improves the biochemical response rate. However, the exact mechanism by which Mao-to is effective remains to be established. We conducted a controlled trial to clarify the effects of Mao-to. The study was carried out in 18 patients with chronic hepatitis C, and we examined subjective symptoms, body temperature and cytokines such as interleukin (IL)-beta, IL-1receptor antagonist (ra), IL-6 and TNF-alpha. Each patient received 6 million units of IFN-beta intravenously. Mao-to was given orally just before, just after, and 1 hour after IFN administration. The control study was carried out 6 months after the combination therapy of Mao-to and IFN-beta. The scores for general malaise, arthralgia and discomfort were significantly lower in the combination group than in control group. Body temperature did not significantly differ between the two groups. Plasma IL-6 level and IL-1ra were significantly elevated in the combination group compared to control (P = 0.0057 and 0.0003, respectively). Mao-to did not affect plasma concentrations of IL-1beta and TNF-alpha. We considered the increment of IL-1ra caused by Mao-to is to be one of the key factors involved in reducing the flu-like symptoms accompanying IFN-beta and improving the biochemical response rate.

Adult↗
PubMed2004

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 12 chlorobenzenes.

Total chlorobenzene content of the Halowax mixtures ranged from 1100 to 9800 ng/g. A lower chlorinated Halowax 1031 and 1000 were a several times more contaminated with chlorobenzenes than higher chlorinated Halowax 1001, 1099, 1013, 1014, or 1051. Depending on the type of the Halowax mixture the most contributing amongst of chlorobenzene homologue groups were di-, tetra-, penta-, and hexa-CBz. A dominance and specific profile of 1,4-DiCBz, PeCBz, and HCBz were characteristic to Halowax 1001, 1099, 1013, 1014, and 1051, while for other formulation the CBzs profile varied, and 1,2,3,4-TeCBz (Halowax 1031) and 1,4-DiCBz (Halowax 1000) predominated. A steric hindrance effect seems to direct a preferential by-side formation of 1,4-DiCBz and further also of PeCBz and HCBz due to relatively elevated temperature as well as duration time of synthesis for five most chlorinated (49-70 Cl%) chloronaphthalene Halowax formulations.

Chlorobenzenes↗
PubMed2004

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 19 chlorophenols.

All seven Halowax formulations examined were contaminated with chlorophenols (CPhs). The total CPhs content of the CN mixtures ranged from 1050 to 34,200 ng/g. The absolute concentration of CPhs decreased with an increase of degree of chlorination (% Cl) of the Halowax 1031 (27%), 1000 (35%), 1001 (49%), and 1099 (51%), respectively, but remained relatively constant for higher chlorinated Halowax 1099 (51%), 1013 (54%), 1014 (59%), and 1051 (70%). 2,4,6-TrCPh and 2,4-DiCPh did contaminated all seven Halowax formulations and PeCPh remained undetected (<90 ng/g) only in Halowax 1099, while less frequently occurred 2,6-DiCPh and followed by 3-/4-MoCPh, 2,5-DiCPh, 2-MoCPh, 2,3-DiCPh, and 2,3,4,6-TeCPh. The CPh congeners such as 3,4-DiCPh, 3,5-DiCPh, 2,3,4-TrCPh, 2,3,5-TrCPh, 2,3,6-TrCPh, 2,4,5-TrCPh, 3,4,5-TrCPh, 2,3,4,5-TeCPh, and 2,3,5,6-TeCPh were undetected in any of the Halowax formulation examined. The profile (%) of higher chlorinated CPh homologues like PeCPh in the Halowaxes followed somehow a degree of chlorination (Cl %) of the parent mixture, i.e., increased from 14, 22, 43, 55, 52 to 80%, respectively, but exception was free of PeCPh the Halowax 1099. And contrary, for a lower chlorinated DiCPhs and TrCPhs their relative proportions decreased but again an exception was Halowax 1099. The fingerprint profiles of 2,4,6-TrCPh, 2,4-DiCPh, and PeCPh, which were usually the most abundant congeners varied and were less consisted when compared to the CPh homologue group profiles, and also more depended on the type of technical Halowax mixture. Due to absence of 2,4,5-TrCPh but presence of 2,4-DiCPh, 2,6-DiCPh, 2,4,6-TrCPh, and PeCPh, which, respectively, are indicative congeners for CPhs obtained by alkaline hydrolysis of chlorobenzenes or phenol chlorination using gaseous chlorine, just co-occurrence of phenol impurity in technical naphthalene is suggested as a solely source of CPhs in the Halowax mixtures.

Chlorophenols↗
PubMed2004

By-side impurities in chloronaphthalene mixtures of the Halowax series: all 209 chlorobiphenyls.

202 congeners of chlorobiphenyl (CB) with 109 single-resolved compounds and 93 co-eluting, which represented from mono- to deca-CB were quantified as by-side impurities in all seven and of various type the technical chloronaphthalene (CN) formulations of the Halowax series. IUPAC No. 104, 145, 159, 169, 184, 186, and 188 were undetected (<0.05-<0.7 ng/g). The total CBs content of the Halowax formulations ranged between 220 and 640,000 ng/g, and lower chlorinated Halowaxes 1031 (27% Cl) and 1000 (35% Cl) were two to three orders of magnitude more contaminated with CBs than higher chlorinated Halowax 1001, 1099, 1013, 1014, and 1051 (49-70% Cl). The profile of CB homologue groups of the Halowaxes changed and followed somehow a degree of chlorination of the parent CN mixture. For Halowax 1031 and 1000, a decreasing trend in proportion from mono- to deca-CB was evident, while for Halowax 1001, 1099, 1013, 1014, and 1051 the relative proportions between the CB homologue groups varied somehow. Evidently content of lower chlorinated mono- and di-CBs highly decreased and steadily increased tri- to octa-CBs and they become dominating homologues in Halowax formulations in parallel with an increase of the content of higher molecular weight CN constituents, respectively. Among planar non- and mono-ortho CBs, total concentrations in Halowax formulations were detected in the range of 2.0-2600 ng/g, and only 3,3',4,4',5,5'-HxCB (no. 169) was undetected (<0.05ng/g). Detection of by-side CBs in technical Halowaxes demonstrate clearly that those formulations apart from a massive introduction of dioxin-like CNs become in the past also an early source of environmental pollution with CBs, which proceeded for around 20-30 years use of original CB formulations.

Environmental Monitoring↗
PubMed2002

Experimental observation of radiation from cherenkov wakes in a magnetized plasma.

A proof-of-principle experiment demonstrates the generation of radiation from the Cherenkov wake excited by an ultrashort- and ultrahigh-power pulse laser in a perpendicularly magnetized plasma. The frequency of the radiation is in the millimeter range (up to 200 GHz). The intensity of the radiation is proportional to the magnetic field intensity as expected by theory. Polarization of the emitted radiation is also detected. The difference in the frequency of the emitted radiation between these experiments and previous theory can be explained by the electrons' oscillation in the electric field of a narrow column of ions in the focal region.

Journal Article↗
PubMed2002

The casein mRNA decay changes in parallel with the poly(A) tail length in the mouse mammary gland.

Using beta- and gamma-casein mRNAs, the relationship between poly(A) tail length and half-life of mRNA is determined in the mouse mammary gland during pregnancy and lactation. beta- and gamma-Casein mRNAs increase before and after parturition, respectively. The poly(A) tail as well as the half-life of casein mRNA becomes longer upon the active casein mRNA synthesis. The poly(A) tail is shortened gradually as lactation progresses. The half-life of mRNA decreases approximately from 20 h at early to 4 h at late lactation. Northern blot analysis reveals that nuclear RNA has the same poly(A) tail length as casein mRNA in the cytoplasm does. Thus, the mammary gland changes the poly(A) tail length of casein mRNA. The poly(A) tail length changes in parallel with the level of poly(A) polymerase (PAP) mRNA during pregnancy and lactation, suggesting that the mammary gland determines the poly(A) tail length of casein mRNA through the change in the PAP gene expression. As the half-life of casein mRNA is related with the degree of polyadenylation, we conclude that the poly(A) tail elongation and shortening is a mechanism in regulating the mRNA decay.

Amanitins↗
PubMed2002

Reconstruction of an amputated fingertip by a prefabricated free volar forearm flap.

An amputated fingertip was banked temporarily under the skin of the volar wrist. This prefabricated fingertip was transferred back to the finger 2 months later, together with a free flap from the volar wrist based on the superficial palmar branch of the radial artery. The fingertip pulp showed a little pale pigmentation, but maintained its length well. The dorsal tip of the finger looked normal. This two-stage procedure made it possible to salvage the amputated bone and nail.

Adolescent↗
PubMed2002

Incidence and clinical features of liver injury related to Kampo (Japanese herbal) medicine in 2,496 cases between 1979 and 1999: problems of the lymphocyte transformation test as a diagnostic method.

We retrospectively examined the summaries of all admission records of patients from 1979 to 1999 in our department, and selected for further study all liver injuries suspected of being related to Kampo medicines. Among 2,496 summaries, 30 summaries described liver disorders suspected of being related to Kampo medicines. Whether there was a causal relationship between the use of Kampo medication and the occurrence of liver injury was assessed according to the criteria described by Haller and Benowitz (2000), independently of the results of the lymphocyte transformation test (LTT). Among 30 events, we concluded that 9 were definitely unrelated, and 6 were probably unrelated to the use of Kampo medicines. Nine events (0.36% of 2,496 patient admissions and 0.06% of 14,616 outpatients) were considered possibly related, and only 6 events (0.24% of 2,496 patient admissions and 0.04% of 14,616 outpatients) were judged to be definitely or probably related to Kampo medicines. Low-grade eosinophilia was observed in a few patients of these "related" groups, and no fever or rash was observed in these "related" groups. Other clinical features, including type of liver injury, duration of Kampo medicine-use, recovery period and laboratory data, were not different from liver injuries associated with western drugs. Most patients in the definitely "unrelated" group were positive in the LTT for the suspect Kampo medicine, suggesting that the LTT may be unreliable for the diagnosis of Kampo-medicine-induced liver injury. From 1979 to 1999, our use of Kampo medicines to treat patients resulted in a low rate of liver injury and no fatalities.

Adolescent↗
PubMed2002

A comparative study between excess-dose users and regular-dose users of rhubarb contained in Kampo medicines.

With prolonged use of rhubarb-containing Kampo medicines, some patients come to ask for high-dose rhubarb because of deteriorated reactivity to rhubarb. We divided patients into two groups in terms of rhubarb-dose, and compared clinical backgrounds between regular-dose group and excess-dose group. Patients who were treated with rhubarb-containing Kampo extracts (manufactured prescriptions) or Kampo formulae (decoctions) for more than 12 months were enrolled. These two groups were compared for age, sex, shape of stool, abdominal symptoms, existence of hemorrhoids, Kampo diagnosis of abdomen, past stimulant laxative use, duration of stimulant laxative use before the first administration of rhubarb, duration of rhubarb use in our hospital, and initial existence of stimulant pain caused by taking stimulant laxatives for the first time. No significant difference was shown between the two groups in terms of age, duration of stimulant laxative-use before the first prescription of rhubarb, shape of stool, abdominal symptoms, existence of hemorrhoids, or duration of rhubarb-use. However, most patients in the regular-dose group had initial stimulant pain of the abdomen upon taking stimulant laxatives for the first time, but most patients in the excess-dose group did not (p < 0.001). All patients except one in the regular dose group had the sign of "umbilical region tenderness on pressure", but half of the excess-dose group did not have it (p = 0.041). Based on these findings, the absence of "initial stimulant pain" and the absence of "umbilical region tenderness on pressure" may predict increasing or excess use of rhubarb, and long-term use of rhubarb should be discouraged more strongly in the patients without these signs.

Cathartics↗
PubMed2002

Correlation of immunologic status with high-resolution CT and distributions of pulmonary tuberculosis.

PURPOSE: To investigate the correlation of cluster of differentiation (CD)4 lymphocyte counts with high-resolution CT (HRCT) findings and distribution of pulmonary tuberculosis. MATERIAL AND METHODS: Thirty-seven bacteriologically proven pulmonary tuberculosis, clinically non-AIDS, patients underwent HRCT and CD4 lymphocyte counts in peripheral blood cells were obtained within 3 days after the CT examinations. Patients were categorized into four groups according to CD4 lymphocyte counts (A >800; B 800-500; C 500-200; D <200). HRCT findings analyzed were as follows: typical, atypical, and mixed findings of post-primary tuberculosis, common, uncommon, and mixed distribution, and number of lobes involved. RESULTS: CD4 lymphocyte counts correlated with the degree of the mixture of atypical CT findings (rho=0.565, p<0.001) and the degree of the mixture of uncommon distribution (rho=0.431, p<0.01). Number of involved lobes showed no statistically significant correlation (rho=0.209, p=0.21). CONCLUSION: In patients with low CD4 levels, atypical HRCT findings co-exist with typical findings, and uncommon sites are involved in addition to common sites.

Adult↗
PubMed2002

Differential diagnosis between thymoma and non-thymoma by dynamic MR imaging.

PURPOSE: To evaluate the usefulness of dynamic MR imaging for differential diagnosis of anterior mediastinal tumors. MATERIAL AND METHODS: Fifty-nine patients with anterior mediastinal tumors were examined. According to histological diagnosis confirmed by surgery or biopsy, 31 had thymomas and 28 had non-thymoma lesions. The patients underwent dynamic MR imaging with gadopentetate dimeglumine administered as a bolus injection. Sequential images were obtained at 30-s intervals for 5 min. Significant differences in the mean peak times of time intensity curves (TICs) were found by histological type, using the Mann-Whitney test. RESULTS: The mean peak time of the TIC was 1.5 min in thymoma and 3.2 min in non-thymoma cases. The difference was statistically significant. Stages I and II of thymoma showed a mean value of 1.3 min, which was significantly shorter than that of 2.5 min in stage III. Differentiation of thymoma/non-thymoma based on the peak time of dynamic MR imaging showed optimal sensitivity (79%) and specificity (84%) when defining thymomas as lesions having peak time appearing earlier than 2 min and non-thymomas later than 2.5 min, with an accuracy of 81%. CONCLUSION: Dynamic MR imaging may improve the differential diagnosis between thymoma and non-thymoma and the staging of thymoma.

Adolescent↗
PubMed2001

Prognostic value of performance status assessed by patients themselves, nurses, and oncologists in advanced non-small cell lung cancer.

Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable, advanced non-small cell lung cancer were investigated prospectively. Weighted Kappa statistics for inter-observer agreement were 0.53 between oncologists and patients and 0.63 between oncologists and nurses. There was a significant difference among the assessments by the three groups (P < 0.001). Oncologists gave the healthiest performance status assessment, nurses an intermediate assessment, and patients the poorest. When included separately in the Cox model, the assessment by each group was significantly correlated with survival. However, the assessment by the patients themselves failed to distinguish survival of patients with performance status 1 and 2. Among the three models including patient-, nurse-, and oncologist-assessed PS, that including oncologist-assessed PS best fitted to the observed survival data. These results showed that the assessment by the patients themselves is different from those by the nurses and the oncologists and provided additional support for the use of the assessment by oncologists in clinical oncology.

Aged↗
PubMed2001

Enhancer regions of ovine interferon-tau gene that confer PMA response or cell type specific transcription.

Interferon-tau (IFNtau), produced by the trophectoderm of peri-implantation conceptuses in ruminant ungulates, attenuates the uterine production of a luteolytic factor, prostaglandin F(2alpha), resulting in the maintenance of corpus luteum function. However, molecular mechanisms regulating the temporal/spatial expression of IFNtau gene are not clearly understood. The 5'-upstream region of the sheep IFNtau (oIFNtau) gene was examined for its transcriptional regulation in two different cell types; JEG3 cells supported the transactivation of oIFNtau-reporter construct, but HeLa cells did not. In a heterologous SV40 enhancer-oIFNtau promoter or oIFNtau enhancer-SV40 promoter systems, elements required for such cell specific transactivation were localized between -654 and -555 bases, the enhancer, but not the basal promoter region of the oIFNtau gene. In these combinations, high degrees of transactivation were observed in JEG3 cells and the activity was further enhanced by the addition of phorbol 12-myristate 13-acetate (PMA), while those responses were absent in HeLa cells. To identify nucleotide sequences responsible for cell specific expression, transient transfection studies with sequential point mutations in the enhancer elements were executed. Transactivation of oIFNtau enhancer-reporter constructs was primarily regulated by three regions containing AP-1 site, GATA like sequence and site(s) unidentified. In gel mobility shift assays (GMSAs), the AP-1 site located in the enhancer region was recognized by nuclear extracts from both cell types. However, one of the GMSA probes containing GATA-like sequence exhibited different DNA-protein complex patterns in JEG3 and HeLa cells. Observations, in which the same upstream sequence behaved differently due possibly to kinds of nuclear factors available in these cell lines, suggest that such a sequence may be involved in cell specific transactivation of the oIFNtau gene. Furthermore, the same enhancer sequences were also recognized by nuclear extracts from sheep trophoblasts, suggesting that the enhancer sequences between -654 and -555 bases of oIFNtau gene may be functioning in vivo.

Animals↗
PubMed2001

Hormonal regulation of mitochondrial Tim23 gene expression in the mouse mammary gland.

Tim23, a mitochondrial inner membrane protein, is essential for cell viability. Mouse Tim23 cDNA consisted of 1142 nucleotides plus poly(A) at the 3' end. In situ hybridization showed that mammary epithelial cells expressed Tim23 mRNA during pregnancy. In order to examine the hormonal regulation of the Tim23 gene expression at lactogenesis, the quantity of Tim23 mRNA in the mammary gland was determined by the competitive RT-PCR. The level of Tim23 mRNA was low until mid-pregnancy, increased toward the end of pregnancy and was the highest on day 18 of pregnancy. On day 13 of pregnancy, Tim23 mRNA increased 2.7-fold between 8 and 16 h after ovariectomy but this increase was cancelled out by the simultaneous operation of adrenalectomy. In adreno-ovariectomized mice, the administration of cortisol increased Tim23 mRNA 2-fold but with progesterone, the stimulatory action of cortisol was no longer observed. The results indicated that the expression of the Tim23 gene became active in response to glucocorticoid.

Animals↗
PubMed2001

Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of irinotecan combined with carboplatin, to evaluate its efficacy and toxicity for patients with lung cancer, and to examine its pharmacokinetics and pharmacodynamics. METHODS: The dose of irinotecan was escalated from 40 mg/m2 per week in increments of 10 mg/m2. Carboplatin was fixed at 300 mg/m2. Multivariate regression models with an interaction term were used to evaluate synergistic pharmacodynamic interactions. RESULTS: The MTD and recommended dose of irinotecan were 60 and 50 mg/m2, respectively. Dose-limiting toxicities were grade 4 neutropenia and grade 3 or 4 diarrhea. In phase II studies, response rates were 81.3% (95% confidence interval 61.8-100%) in 16 patients with small-cell lung cancer and 22.2% (2.7-41.8%) in 18 patients with non-small-cell lung cancer. Two patients (6%) experienced grade 4 neutropenia, thrombocytopenia, and grade 3 diarrhea. The area under the plasma concentration versus time curve (AUC) of carboplatin ranged from 2.87 to 9.31 mg x min/ml, with a median of 4.66 mg x min/ml. In pharmacodynamic analyses, the log-transformed surviving fraction in platelet count (SFp) showed a significant association with the AUC of carboplatin (P=0.010), while that in neutrophil count (SFn) was not significantly correlated with any pharmacokinetic parameter. The interaction term was not significant in either case. CONCLUSIONS: These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy. A more sensitive method for predicting life-threatening toxicities is needed, however, because traditional pharmacokinetic parameters were not adequate tools for identifying patients at high risk of severe neutropenia and diarrhea. This combination regimen has only modest activity, and further studies are necessary to evaluate a different dose schedule.

Adult↗
PubMed2001

MR imaging findings of uterine endometrial stromal sarcoma: differentiation from endometrial carcinoma.

Endometrial stromal sarcoma (ESS) is a rare malignant neoplasm of the uterus. We retrospectively analyzed pelvic MR imaging in 8 cases of ESS to determine the characteristic MR findings of ESS. Magnetic resonance images of 8 cases of ESS were evaluated for findings including the size, margin of the tumor, nodular lesions at the tumor margin, intramyometrial worm-like nodular extension, multiple nodular mass formation, hemorrhage, and necrosis in the tumor. The degree of contrast enhancement was also analyzed. The MR imaging findings of 21 consecutive cases of endometrial carcinoma (EC) were also evaluated and compared with those of ESS. The mean and the standard deviation of the maximum diameter of ESS and EC were 8.80 +/- 4.99 and 3.93 +/- 2.47 cm, respectively. Increased enhancement in at least a part of the tumor was observed in five of the six analyzed ESS cases and in 2 of 12 analyzed EC cases. The irregular margin, nodular lesions at the margin, intramyometrial nodular extension, and multiple nodular mass formation were more frequently seen in cases of ESS than in cases of EC. Magnetic resonance imaging can play a role in both diagnosing ESS as well as in differentiating ESS from EC.

Aged↗