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Articles by M Hashimoto
Total Records ( 5 ) for M Hashimoto
  Y Kushi , H Kamimiya , H Hiratsuka , H Nozaki , H Fukui , M Yanagida , M Hashimoto , K Nakamura , S Watarai , T Kasama , H Kajiwara and T. Yamamoto
 

Bacterial sialyltransferases (STs) from marine sources were characterized using glycosphingolipids (GSLs). Bacterial STs were found to be β-galacotoside STs. There were two types of STs: (1) ST obtained from strains such as ishi-224, 05JTC1 (#1), ishi-467, 05JTD2 (#2), and faj-16, 05JTE1 (#3), which form 2-3 sialic acid (Sia) linkages, named 2-3ST, (2) ST obtained from strains such as ISH-224, N1C0 (#4), pda-rec, 05JTB2 (#5), and pda-0160, 05JTA2 (#6), which form 2-6 Sia linkages, named 2-6ST. All STs showed affinity to neolacto- and lacto-series GSLs, particularly in neolactotetraosyl ceramide (nLc4Cer). No large differences were observed in the pH and temperature profiles of enzyme activities. Kinetic parameters obtained by Lineweaver–Burk plot analysis showed that #3 and #4 STs had practical synthetic activity and thus it became easily possible to achieve large-scale ganglioside synthesis (100–300 µM) using these recombinant enzymes. Gangliosides synthesized from nLc4Cer by 2-3 and 2-6STs were structurally characterized by several analytical and immunological methods, and they were identified as IV3NeuAc-nLc4Cer(S2-3PG) and IV6NeuAc-nLc4Cer (S2-6PG), respectively. Further characterization of these STs using lactotetraosylceramide (Lc4Cer), neolactohexaosylceramide (i antigen), and IV6kladoLc8Cer (I antigen) showed the synthesis of corresponding gangliosides as well. Synthesized gangliosides showed binding activity to the influenza A virus [A/panama/2007/99 (H3N2)] at a similar level to purified S2-3PG and S2-6PG from mammalian sources. The above evidence suggests that these STs have unique features, including substrate specificities restricted to lacto- and neolactoseries GSLs, as well as catalytic potentials for ganglioside synthesis. This demonstrates that efficient in vitro ganglioside synthesis could be a valuable tool for selectively synthesizing Sias modifications, thereby permitting the exploration of unknown functions.

  K Ichiyama , M Hashimoto , T Sekiya , R Nakagawa , Y Wakabayashi , Y Sugiyama , K Komai , I Saba , T Moroy and A. Yoshimura
 

Th cells have long been divided into two subsets, Th1 and Th2; however, recently, Th17 and inducible regulatory T (iTreg) cells were identified as new Th cell subsets. Although Th1- and Th2-polarizing cytokines have been shown to suppress Th17 and iTreg development, transcriptional regulation of Th17 and iTreg differentiation by cytokines remains to be clarified. In this study, we found that expression of the growth factor independent 1 (Gfi1) gene, which has been implicated in Th2 development, was repressed in Th17 and iTreg cells compared with Th1 and Th2 lineages. Gfi1 expression was enhanced by the IFN-/STAT1 and IL-4/STAT6 pathways, whereas it was repressed by the transforming growth factor-β1 stimulation at the promoter level. Over-expression of Gfi1 strongly reduced IL-17A transcription in the EL4 T cell line, as well as in primary T cells. This was due to the blockade of recruitment of retinoid-related orphan receptor t to the IL-17A promoter. In contrast, IL-17A expression was significantly enhanced in Gfi1-deficient T cells under Th17-promoting differentiation conditions as compared with wild-type T cells. In contrast, the impacts of Gfi1 in iTregs were not as strong as in Th17 cells. Taken together, these data strongly suggest that Gfi1 is a negative regulator of Th17 differentiation, which represents a novel mechanism for the regulation of Th17 development by cytokines.

  M Hashimoto , T Iimoto and T. Kosako
 

A novel neutron dose measurement method that flexibly responds to variations in the neutron field is being developed by Japan Atomic Energy Agency. This is an implementation of the multi-detector method (first introduced in 1960s) for neutron dose evaluation using a convex hull in the response space defined for multiple detectors. The convex hull provides a range of possible neutron dose corresponding to the incident neutron spectrum. Feasibility of the method was studied using a simulated response of mixed gas proportional counter. Monochromatic neutrons are shown to be fundamentally suitable for mapping the convex. The convex hull can be further reduced taking into consideration a priori information about physically possible incident neutron spectra, for example, theoretically derived moderated neutron spectra originated from a fission neutron source.

  T Fujibuchi , N Funabashi , M Hashimoto , H Kato , M Kurokawa , H. M Deloar , E Kunieda , I Komuro and T. Sakae
 

Organ absorbed doses in computed tomography (CT) scans can be measured with anatomical phantoms but not inside the human body. In this study, a straightforward method was investigated to estimate organ doses in clinical CT using the radiation treatment planning system (RTPS) and compared them with experimental results of photoluminescence dosemeters (PLD). In a heterogeneous phantom, the average difference between PLD and RTPS values were –5.0 % for the body and 7.1 % for the lung. Using CT data, organ doses in 30 clinical cases were then calculated. There was a significant inverse correlation between the calculated values of organ doses and body mass index (BMI, correlation coefficients (r)=–0.69 (whole body), –0.80 (right lung), –0.81 (left lung), –0.76 (spinal cord), –0.74 (vertebra bone), –0.74 (heart), and –0.79 (oesophagus), all p < 0.01). An RTPS can be a simple and useful tool for estimating equivalent doses inside the human body, during whole-body CT scans.

  Y Okumura , F Tanaka , K Yoneda , M Hashimoto , T Takuwa , N Kondo and S. Hasegawa
  Background

Circulating tumor cells in peripheral blood (CTC) is a potential surrogate of distant metastasis, which is the critical factor influencing decision making regarding therapy and prognosis of primary lung cancer patients. After our preliminary study showing that CTCs were detected in peripheral blood in 29.4% of resectable lung cancer patients, we conducted a prospective study on CTC in pulmonary vein (PV) blood because tumor cells apart from the primary tumor may circulate after passing through the drainage PV.

Methods

A total of 30 consecutive lung cancer patients who underwent thoracotomy were included. The CTCs in peripheral blood and in PV blood from the primary tumor site were quantitatively examined with the CellSearch system, and the numbers of CTCs per 7.5 mL peripheral and PV blood in each patient were represented as periCTC count and pvCTC count, respectively.

Results

Circulating tumor cell was detected in peripheral blood in 5 patients (16.7%; the periCTC count was 1 in 2 patients; and 2, 3, and 16 in 1 patient each), and the incidence of positive periCTC was higher in squamous carcinoma patients than in adenocarcinoma patients (p = 0.028). Circulating tumor cell was detected in PV blood in most patients (29 of 30, 96.7%), and the mean and median pvCTC counts were 1,195 and 81, respectively (range, 0 to 10,034). There was no significant correlation between pvCTC count and any other patient characteristic, including periCTC count.

Conclusions

In resectable lung cancer, CTC was positive in peripheral blood of some patients and in PV blood of most patients. A long-term follow-up study to clarify the clinical significance of pvCTC status is warranted.

 
 
 
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