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Biomedical subjects

T Hara

Publications and source records attributed to T Hara.

At least 127 records · Page 7Linked to original sources

Observation of large CP violation in the neutral B meson system.

We present a measurement of the standard model CP violation parameter sin2 phi(1) based on a 29.1 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is fully reconstructed as a J/psi K(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psi K(L), or J/psi K(*0) decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin2 phi(1) = 0.99+/-0.14(stat)+/-0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.

Journal Article↗

Clinical and biologic characteristics for recurring neuroblastoma at mass screening cases in Japan.

BACKGROUND: It is said that most cases detected by neuroblastoma mass screening at 6 months of age tend to have a favorable clinical course after a surgical resection either with or without mild chemotherapy. However, a few cases have an unfavorable outcome. In the current study, the authors analyzed the clinical and biologic characteristics for recurring neuroblastoma in mass screening cases. METHODS: In 245 cases detected through mass screening in the Kyushu area in Japan, the clinical data and biologic features (N-myc status, DNA ploidy, Shimada histology, neuron-specific enolase (NSE), ferritin) were investigated, whereas, in particular, the data for recurring cases also were analyzed. RESULTS: Of 245 cases, 28 tumors had one or more biologically unfavorable prognostic factors, and 6 patients experienced recurrence. Three of the six patients with recurring disease underwent a complete resection of the primary tumor, whereas three cases had undergone an incomplete resection of the tumor. Regarding the initial chemotherapy, three cases received mild chemotherapy, two cases received no chemotherapy, and one case had high-dose multidrug chemotherapy. Regarding biologic prognostic factors, four of six cases with recurring disease had one or more unfavorable factors, whereas two cases had no unfavorable factors. Regarding the outcome after recurrence, four cases are CR, one case has a stable residual tumor, and one case died of disease with N-myc amplification. CONCLUSIONS: Most neuroblastomas detected by mass screening at 6 months of age have biologically favorable factors. However, approximately 10% of the cases had one or more unfavorable factors and thus might have a higher risk of recurrence than the patients with no unfavorable factors. Conversely, some cases with recurring disease had no unfavorable factors; however, the reason for this is still unclear. A long-term follow-up for mass screening cases is important, and it also might be necessary to research the established biologic factors and identify other new prognostic factors.

Antineoplastic Combined Chemotherapy Protocols↗

Relation between breastfeeding and the prevalence of asthma : the Tokorozawa Childhood Asthma and Pollinosis Study.

Many risk factors for asthma have been proposed including age, gender (male), smoking, and family history of asthma. The importance of breastfeeding to childhood asthma is a controversial issue. The present study investigated the relation between breastfeeding and the prevalence of asthma among a childhood population. The subjects were 25,767 students, representing all public elementary and junior high schools in Tokorozawa, Japan (age range, 6--15 years). The study population included 2,315 students with asthma and 21,513 controls. Participants' parents completed the Japanese version of the American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute, questionnaire for children adopted by the Japanese Environmental Agency in 1998. The authors added supplementary questions on the parental history of asthma and feeding patterns from the age of 0--3 months. The risk of breastfeeding for asthma was compared with that of artificial feeding. After adjustment for age, gender, parental smoking status, and parental history of asthma, a significantly higher prevalence of asthma was noted among children who had been breastfed (adjusted odds ratio = 1.198; 95% confidence interval: 1.054, 1.363; p for trend < 0.01). The results indicated that breastfeeding in infancy might be related to the higher prevalence of asthma during preadolescence.

Adolescent↗

Quick quantitative analysis of gene dosages associated with prognosis in neuroblastoma.

The amplification of the N-myc gene and a gain of the chromosome 17q arm correlate with an unfavorable outcome in patients with neuroblastoma. In this study, we determined the gene dosage of the N-myc gene (located at 2p24) and Survivin gene (located at 17q25) using the p53 gene (located at 17p13) as the internal control gene by the TaqMan polymerase chain reaction (PCR)-based gene dosage analysis in 25 neuroblastoma samples. Based on the assumption that the gene dosages of each gene of a normal individual lymphocytes are 1.0, 11 of the 25 cases with a corrected gene dosage of N-myc (N-myc/p53) of more than 2.0 had a more unfavorable prognosis than the 14 cases with a N-myc gene dosage of less than 2.0 (5-year survival rate: 18 vs. 71%, P<0.01). Ten of 25 cases with a corrected Survivin gene dosage (Survivin/p53) of more than 2.0 had a more unfavorable prognosis than the 15 cases with a Survivin gene dosage of less than 2.0 (5-year survival rate: 10 vs. 67%, P<0.01). This quantitative PCR system is considered to be useful for quickly and accurately evaluating the degree of malignancy of neuroblastoma in order to select the optimal treatment.

Child↗

Caspase-dependent cytosolic release of cytochrome c and membrane translocation of Bax in p53-induced apoptosis.

Activation of p53 induces apoptosis in various cell types. However, the mechanism by which p53 induces apoptosis is still unclear. We reported previously that the activation of a temperature-sensitive mutant p53 (p53(138Val)) induced activation of caspase 3 and apoptosis in Jurkat cells. To elucidate the pathway linking p53 and downstream caspases, we examined the activation of caspases 8 and 9 in apoptotic cells. The results showed that both caspases were activated during apoptosis as judged by the appearance of cleavage products from procaspases and the caspase activities to cleave specific fluorogenic substrates. The significant inhibition of apoptosis by a tetrapeptide inhibitor of caspase 8 and caspase 9 suggested that both caspases are required for apoptosis induction. In addition, the membrane translocation of Bax and cytosolic release of cytochrome c, but not loss of mitochondrial membrane potential, were detected at an early stage of apoptosis. Moreover, Bax translocation, cytochrome c release, and caspase 9 activation were blocked by the broad-spectrum caspase inhibitor, Z-VAD-fmk and the caspase 8-preferential inhibitor, Ac-IETD-CHO, suggesting that the mitochondria might participate in apoptosis by amplifying the upstream death signals. In conclusion, our results indicated that activation of caspase 8 or other caspase(s) by p53 triggered the membrane translocation of Bax and cytosolic release of cytochrome c, which might amplify the apoptotic signal by activating caspase 9 and its downstream caspases.

Apoptosis↗

An experimental study on the interface strength between titanium mesh cage and vertebra in reference to vertebral bone mineral density.

STUDY DESIGN: Using human cadaver spines, the authors investigated mechanical properties of the interface between titanium mesh cage and vertebra in respect to vertebral bone mineral density. OBJECTIVES: The objective of this study is to examine the effects of the size of the mesh cage and an internal end ring system on interface mechanical properties in reference to vertebral bone mineral density. SUMMARY OF BACKGROUND DATA: A titanium mesh cage has recently been developed for anterior spinal reconstruction. The cage provides immediate postoperative stability and facilitates bony union with cancellous bone packed in the cage itself. Mechanical properties of the interface between the cage and vertebra, however, are yet to be clarified in osteoporotic spine. METHODS: Twenty-five lumbar vertebrae harvested from embalmed human cadavers (n = 20) were used. The vertebrae were divided into four experimental groups according to the applied cage conditions: Phi25 mm cage without internal end ring (L-), Phi19 mm cage without internal end ring (S-), Phi25 mm cage with internal end ring (L+), and Phi19 mm cage with internal end ring (S+). Bone mineral density of whole vertebral body was measured by dual energy radiograph absorptiometer (DXA). Peripheral quantitative computed tomography was used to determine local bone mineral density of subchondral cancellous bone of vertebral body. Each cage was compressed on vertebral endplate via a specially designed device connected to a material testing machine. Maximum load and stiffness of the interface between the cage and vertebra were measured from load-deformation data in quasi-static compression loading with a loading rate of 0.5 mm/min. Relationships between the mechanical properties and vertebral bone mineral densities were evaluated. In 11 specimens acoustic emission during compression loading was measured and simultaneously recorded in load-deformation data. After the mechanical test microradiograms of midsagittal sections of the vertebrae were taken to observe failure patterns of endplate or trabecular bone. RESULTS: Vertebrae compressed with large cages (group: L- or L+) showed greater maximum load than those compressed with small cages (group: S- or S+). The internal end ring contributed to higher maximumload. The size of the cage or the internal end ring, however, did not have any effect on stiffness. Maximum load and stiffness were positively correlated with whole vertebral bone mineral density measured by dual energy radiograph absorptiometer or local cancellous bone mineral density of subchondral bone measured by peripheral quantitative computed tomography. Correlation coefficient and P value were more significant in the association of the mechanical properties and subchondral bone mineral density measured by peripheral quantitative computed tomography than in the association of the parameters and whole vertebral bone mineral density measured by DXA. A load-deformation curve with an acoustic emission event count rate showed that significant acoustic emission signals were generated around maximum load. On microradiographic study most vertebrae compressed with the cage showed encroachment of the cage spikes into the endplate or trabecular structure, preserving structures of the most central portion of the vertebrae. CONCLUSION: A titanium mesh cage with larger diameter and/or augmentation of internal end ring produces a significant increase of the interface strength between the cage and the vertebra. A positive correlation between the interface strength and vertebral bone mineral density suggests that vertebral bone mineral density is an important parameter for successful spinal reconstruction, and also implies that in severe osteoporotic spine the stability of the cage is declined, and other instrumentation should be combined.

Aged↗

Presence of multiple HIV type 1 subtypes among mothers and children in Japan.

We collected blood samples from 70 HIV-1-infected pregnant women and 76 babies born to HIV-1-infected women in Japan, from 1989 to 1999. To analyze the genetic diversity of HIV-1 among mothers and children, we sequenced the C2-V3 regions of HIV-1 gp120. Phylogenetic tree analysis of these regions revealed that multiple HIV-1 subtypes, A, B, D, E, and G, were circulating among mothers and children in Japan. Thus, the genetic heterogeneity of HIV-1 among mothers and children in Japan is steadily increasing, although the number of cases remains small. Perhaps the longest term survivor, an 11-year-old child with a vertical HIV-1 subtype G infection in Japan, is one of our subjects.

Amino Acid Sequence↗

Measurement of B(0)(d)-B_(0)(d) mixing rate from the time evolution of dilepton events at the upsilon(4S).

We report a determination of the B(0)(d)-&B_(0)(d) mixing parameter Deltam(d) based on the time evolution of dilepton yields in Upsilon(4S) decays. The measurement is based on a 5.9 fb(-1) data sample collected by the Belle detector at KEKB. The proper-time difference distributions for same-sign and opposite-sign dilepton events are simultaneously fitted to an expression containing Deltam(d) as a free parameter. Using both muons and electrons, we obtain Deltam(d) = 0.463+/-0.008 (stat)+/-0.016 (syst) ps(-1). This is the first determination of Deltam(d) from time evolution measurements at the Upsilon(4S). We also place limits on possible CPT violations.

Journal Article↗

Effects of peptide dimerization on pore formation: Antiparallel disulfide-dimerized magainin 2 analogue.

To elucidate the effects of peptide dimerization on pore formation by magainin 2 (MG2), a covalently linked antiparallel dimer of the MG2 analogue [(F5Y, L6C, F16W, I20C-MG2)(2): II] was synthesized based on the dimer structure revealed by our NMR study. The interactions of the dimer with lipid bilayers were investigated by CD and fluorescence in comparison with a monomer analogue (F5Y, F16W-MG2: I). Similar to I, II was found to form a peptide-lipid supramolecular complex pore accompanied with lipid flip-flop and peptide translocation. The pore formed by II was characterized by a slightly larger pore diameter and a threefold longer lifetime than that of I, although the pore formation rate of the dimer was lower than that of the monomer. The coexistence of the dimer and the monomer exhibited slight but significant synergism in membrane permeabilization, which was maximal at a monomer/dimer ratio of 3. Therefore, we concluded that a pentameric pore composed of one pore-stabilizing dimer and three monomers maximized the overall leakage activity in keeping with our kinetic prediction.

Amino Acid Sequence↗

Measurement of the CP violation parameter sin2 phi(1) in B(0)(d) meson decays.

We present a measurement of the standard model CP violation parameter sin2 phi(1) (also known as sin2beta) based on a 10.5 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) collider. One neutral B meson is reconstructed in the J/psiK(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psiK(L), or J/psipi(0) CP-eigenstate decay channel and the flavor of the accompanying B meson is identified from its charged particle decay products. From the asymmetry in the distribution of the time interval between the two B-meson decay points, we determine sin2 phi(1) = 0.58(+0.32)(-0.34)(stat)+0.09-0.10(syst).

Journal Article↗

XANES analyses of silicon crystalline irradiated by nitrogen/oxygen ions.

X-ray absorption techniques have been applied to the characterization of 5 keV nitrogen / oxygen ions implanted silicon samples. The depth selective measurement of XANES by recording in PEY mode and the quantitative analysis by superposition of XANES spectra were carried out to elucidate the depth profile of implanted ions. It has been revealed that the silicon nitride phase were formed in silicon after prolonged N+ irradiation and it extended over the deep part of the damaged region from the surface. On the other hand, for the O+ irradiation, silicon dioxide phase were produced only in the shallow part of the damaged region, i.e., the silicon dioxide phase likely broke off during the irradiation.

Journal Article↗

Total gastrectomy with distal pancreatectomy and splenectomy for advanced gastric cancer.

BACKGROUND: Pancreaticosplenectomy (PS) is often performed simultaneously with total gastrectomy (TG) to facilitate dissection of the lymph nodes around the splenic artery and splenic hilus. To evaluate the effects of PS on survival, a retrospective study was performed. METHODS: Various clinicopathological factors influencing lymph node metastasis around the splenic hilus (No. 10) and the splenic artery (No. 11) were studied retrospectively in the upper or middle third of advanced gastric cancer patients who underwent TG with PS. The postoperative morbidity, mortality, and survival rate of patients who underwent TG with PS (the TG with PS group) were compared with those of patients who underwent TG alone (the TG-alone group). RESULTS: Tumor size larger than 41 mm and lymph node No. 2 metastasis were independently correlated with lymph node No. 10 and No. 11 metastasis. The mortality rate was similar, but the morbidity rate was significantly higher in the TG with PS group. In the patients with stage I and III, there was no significant difference between the two groups, but in the patients with stage II, the TG-alone group was significantly better than the TG with PS group (P = 0.0400). CONCLUSIONS: Combined PS with TG should never be performed as the standard surgical procedure for every stage of gastric cancer, especially stage II.

Adult↗

Rapid detection of the 22q11.2 deletion with quantitative real-time PCR.

We report the detection of 22q11.2 deletions using TaqMan(TM)PCR-based gene dosage analysis of patients previously diagnosed by fluorescent in situ hybridization (FISH). We performed quantitative PCR of the UFD1L gene from this region and showed a 99.7% statistical correlation between the two methods. The advantages of this method over FISH include: (i) rapidity; (ii) ease; (iii) relatively low cost and; (iv) the small quantities of DNA needed.

Abnormalities, Multiple↗

Quantitative monitoring of circulating Epstein-Barr virus DNA for predicting the development of posttransplantation lymphoproliferative disease.

Epstein-Barr virus (EBV)-DNA was quantitatively measured to assess posttransplantation virus reactivation by real-time polymerase chain reaction (PCR). In the first retrospective analysis of a 7-year-old boy with lymphoproliferative disease (LPD) after an unrelated cord blood transplantation, serum EBV-DNA progressively increased to 4 x 10(5) copies/mL. EBV load was then prospectively monitored in peripheral blood from posttransplantation patients. The second case was an 8 year-old boy with aplastic anemia who received a CD34+ cell transplantation. This patient died of LPD with the progression of pulmonary nodules. EBV-DNA increased to 4 x 10(4) copies/mL after the control of cytomegalovirus reactivation. On the other hand, EBV-DNA was undetectable (<200 copies/mL) in the series of all 58 samples from 10 patients who did not develop LPD after hematopoietic stem cell transplantation. Sequential monitoring of circulating EBV-DNA by quantitative PCR may be a useful indicator for predicting the development of posttransplantation LPD.

Anemia, Aplastic↗

Long-term outcome of treatment with protocols AL841, AL851, and ALHR88 in children with acute lymphoblastic leukemia: results obtained by the Kyushu-Yamaguchi Children's Cancer Study Group.

We analyzed the long-term outcome and late effects of treatment in 187 patients with childhood acute lymphoblastic leukemia (ALL) diagnosed between 1984 and 1990. Overall survival and event-free survival rates were 68.2% +/- 3.7% and 63.2% +/- 3.6% at 15 years, respectively. Of 55 patients who relapsed after achieving the first complete remission (CR), only 17.4% were rescued by salvage therapy. The advantage of stem cell transplantation over chemotherapy was observed only in those patients with bone marrow relapse during therapy. The SD for score height in patients maintaining the first CR significantly decreased at the time of final follow-up compared with that at diagnosis: 0.059 to -0.800 (P < .0001). The decrease was remarkable in patients younger than 5 years at diagnosis. Other late effects included mild liver dysfunction in 18% and hepatitis C virus infection in 9%. Congestive heart failure was observed in only 2.9% of patients despite the high cumulative dose of daunorubicin (450 mg/m2). Although the survival rates of patients on our protocols were comparable to those of other study groups, some modification, including reduction in dose of cranial irradiation and/or anticancer drugs, should be considered to reduce late adverse effects in survivors of childhood ALL.

Adolescent↗

Quantitative analysis of telomerase activity and telomerase reverse transcriptase expression in renal cell carcinoma.

To investigate the relationship between the telomerase activity levels and clinicopathological features of tumors, we quantified the telomerase activities of 23 renal cell carcinomas (RCCs) and four non-cancerous tissues, using a modified telomeric repeat amplification protocol assay, and assessed the hTERT mRNA levels of these samples by reverse transcription-polymerase chain reaction analysis. Elevated levels of telomerase activity had correlation with tumor stages as well as the degree of nuclear grades. Our findings suggested that telomerase activity is a useful indicator for tumor aggressiveness in RCCs. However, hTERT mRNA levels in RCCs had no correlation with nuclear grades and tumor stages. The telomerase activities and the hTERT mRNA levels in cancer cells were not always in parallel. These results suggested that telomerase activity is regulated in a posttranscriptional manner as well as a post-translational manner in tumor cells.

Adult↗