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Biomedical subjects

T Tajima

Publications and source records attributed to T Tajima.

At least 19 recordsLinked to original sources

Identification of DNA markers of tobacco linked to bacterial wilt resistance.

Bacterial wilt caused by Ralstonia solanacearum is one of the most destructive soil-borne diseases in the world. Breeding resistant commercial varieties of tobacco is difficult because most donor candidates' resistance is controlled by polygenes. In this paper, we demonstrate the identification of useful DNA markers for bacterial wilt-resistant tobacco breeding. One hundred and seventeen markers were identified by the amplified fragment length polymorphism (AFLP) method between W6, a burley variety with resistance originating from a Japanese domestic variety, Hatano, and Michinoku 1, a commercial burley wilt-susceptible variety, using 3,072 primer combinations. These markers were analyzed in 125 doubled haploid lines, derived from F(1) hybrids between W6 and Michinoku 1, and a linkage map consisting of ten linkage groups was drawn. The resistance phenotype of each of these lines was investigated on the basis of the average of disease severity obtained from field trials over two growing cycles. Quantitative trait loci (QTL) analysis was performed on the marker phenotypes and the resistance phenotype of each line. One QTL for the bacterial wilt resistance of W6 and DNA markers associated with this QTL were identified on a linkage group consisting of 15 markers, 32 cM in length. This QTL explained more than 30% of the variance in resistance among these lines.

Burkholderia↗

Proposed double-layer target for the generation of high-quality laser-accelerated ion beams.

In order to achieve a high-quality, i.e., monoenergetic, intense ion beam, we propose the use of a double-layer target. The first layer, at the target front, consists of high-Z atoms, while the second (rear) layer is a thin coating of low-Z atoms. The generation of high-quality proton beams from the double-layer target, irradiated by an ultraintense laser pulse, is demonstrated with three-dimensional particle-in-cell simulations.

Ions↗

Particle in cell simulation of laser-accelerated proton beams for radiation therapy.

In this article we present the results of particle in cell (PIC) simulations of laser plasma interaction for proton acceleration for radiation therapy treatments. We show that under optimal interaction conditions protons can be accelerated up to relativistic energies of 300 MeV by a petawatt laser field. The proton acceleration is due to the dragging Coulomb force arising from charge separation induced by the ponderomotive pressure (light pressure) of high-intensity laser. The proton energy and phase space distribution functions obtained from the PIC simulations are used in the calculations of dose distributions using the GEANT Monte Carlo simulation code. Because of the broad energy and angular spectra of the protons, a compact particle selection and beam collimation system will be needed to generate small beams of polyenergetic protons for intensity modulated proton therapy.

Computer Simulation↗

Expression of a novel matrix metalloproteinase gene during Cynops early embryogenesis.

Matrix metalloproteinases (MMPs) are thought to play important roles in the gastrulation of Cynops pyrrhogaster embryos. MMP cDNAs were cloned from Cynops pyrrhogaster and we report here a novel MMP called CyMMP, which has strong similarity to MMP-21 (XMMP) in Xenopus. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated that CyMMP mRNA was already present in cleavage stage embryos. The amount of the mRNA then gradually decreased, but increased again starting in late gastrula. There were regional differences in the level of CyMMP mRNA expression at late gastrula: the involved archenteron roof was the predominant site of expression of the gene, while there was weak expression in the neuroectoderm and epidermal ectoderm. We also found that the gene was activated in artificially mesodermalized ectoderm. The present findings indicate that CyMMP mRNA expression is activated in differentiating mesoderm during gastrulation, suggesting that CyMMP plays a role in gastrulation-related cell movement.

Amino Acid Sequence↗

Detection of tumor cells in the portal and peripheral blood of patients with colorectal carcinoma using competitive reverse transcriptase-polymerase chain reaction.

BACKGROUND: In spite of many reports, it remains unclear whether the presence of tumor cells in circulating blood flow predicts a poor prognosis. METHODS: Competitive seminested reverse transcriptase-polymerase chain reaction (RT-PCR), a technique for the quantitative detection of tumor cells, was applied to detect the presence of tumor cells in portal and peripheral blood samples from 121 patients with colorectal carcinoma and to clarify their clinical significance. This technique can detect one carcinoembryonic antigen (CEA) mRNA-expressing tumor cell in 1 x 10(5) normal lymphocytes. RESULTS: Six of 33 healthy volunteers (18%) demonstrated a positive reaction to this technique. CEA mRNA expression was detected in the portal blood in 51% of patients and in the peripheral blood in 42% of patients. The results from the two blood samples were consistent in 91% of patients. The positive expression rates for portal blood in patients with T1 tumors and those with TNM Stage I disease were 38% and 45%, respectively. The positive rate was significantly higher in patients with colon carcinoma and those with Stage III or IV disease. CEA mRNA expression, quantitatively measured (x 10(-8)/beta-actin), was 22.9 +/- 35.1 in the portal blood and 19.9 +/- 40.0 in the peripheral blood, with no statistically significant difference. A significant positive correlation was noted between portal and peripheral CEA mRNA expression levels according to Spearman correlation analysis (correlation coefficient = 0.78; P < 0.01). Multivariate analysis revealed that the positive rate and level of CEA mRNA expression in the portal and peripheral blood did not appear to be influenced by the established prognostic factors. CONCLUSIONS: The presence of circulating tumor cells might be of less value as a prognostic factor because they also can be detected in patients with early-stage colorectal carcinoma and appeared to be independent of the conventional prognostic factors.

Blood Specimen Collection↗

Liver metastasis from gallbladder carcinoma: anatomic correlation with cholecystic venous drainage demonstrated by helical computed tomography during injection of contrast medium in the cholecystic artery.

BACKGROUND: The current study evaluated whether the sites of liver metastasis from gallbladder carcinoma are correlated with areas of cholecystic venous drainage (CVD) utilizing helical computed tomography (CT) during the injection of contrast medium into the cholecystic artery (cholecystic artery CT). METHODS: Cholecystic artery CT scans were performed in 26 patients with gallbladder carcinoma. Liver metastases were examined retrospectively in these patients on CT, and the sites of liver metastasis and CVD were compared closely. The patients were divided into concurrent (those who had metastasis at the time of cholecystic artery CT), early postoperative metastasis (those who developed metastasis within 6 months after surgery), and late postoperative metastasis (those who developed metastasis more than 6 months after surgery) groups. The frequency of metastasis related to CVD was compared between the three groups. RESULTS: A total of 32 metastases were identified in 11 patients, 21 of which were related to CVD. Six patients were included in the concurrent metastasis group; 18 of 20 tumors were found to be related closely to CVD. There were two patients in the early postoperative metastasis group; all three of the tumors detected were found to be closely related to CVD. Three patients were subclassified as being in the late postoperative metastasis group; none of the nine tumors detected appeared to be in areas associated with CVD. CONCLUSIONS: The sites of liver metastases were found to be well correlated with the areas with CVD, particularly in the concurrent and early postoperative metastasis groups. CVD may be a useful marker of potential areas of liver metastasis from gallbladder carcinoma, particularly in patients with early stage metastasis.

Adult↗

Intraoperative radiation therapy for curatively resected rectal cancer.

PURPOSE: Intraoperative radiotherapy has been used for local control of locally advanced rectal cancer. The aim of this study was to investigate the efficacy of intraoperative radiotherapy for curatively resected rectal cancer. METHODS: Between 1982 and 1998, intraoperative radiotherapy was administered in combination with curative resection in 78 patients with adenocarcinoma of the middle or lower third of the rectum (intraoperative radiotherapy group). Sixty-two of the patients had received preoperative radiotherapy with 20 Gy. Intraoperative radiotherapy was performed by a new strategy in which an electron beam was administered as uniformly as possible to the entire dissected surface of the pelvis. Retrospective comparisons were made with 248 patients treated by surgery alone during the same period (non-intraoperative radiotherapy group). RESULTS: The differences in tumor stage or surgical procedures between the two groups were not statistically significant. Survival, disease-free survival, and local recurrence-free survival in the intraoperative radiotherapy group were significantly more favorable than in the non-intraoperative radiotherapy group (P = 0.01, P = 0.04, and P = 0.02). Differences in survival were observed in Stage II patients but not in Stage I or Stage III patients. The local failure rate was 2.6 percent in the intraoperative radiotherapy group and 11.3 percent in the non-intraoperative radiotherapy group, and the difference was significant (P = 0.02). The distant metastasis rate was 18.0 percent in the intraoperative radiotherapy group and 19.5 percent in the non-intraoperative radiotherapy group, and the difference was not significant. There was a significantly higher rate of wound infection in the intraoperative radiotherapy group, but no infections were serious. CONCLUSIONS: In patients with adenocarcinoma of the middle or lower third of the rectum, intraoperative radiotherapy to the entire dissected surface of the pelvis reduced local recurrence in Stage II and Stage III patients and improved survival in Stage II patients.

Adenocarcinoma↗

Clinical development of trastuzumab in breast cancer.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) is now available for clinical use in the U.S.A. It is also expected to be available in Japan in the near future. In this paper, the details of this novel biologic agent are reviewed in conjunction with a phase I study performed in Japan.

Animals↗

Compassionate use of humanized anti-HER2/neu protein, trastuzumab for metastatic breast cancer in Japan.

The HER-2/neu protein is thought to be a unique and useful target for antibody therapy of cancers overexpressing the HER-2/neu gene. The recombinant humanized anti-HER-2 monoclonal antibody, trastuzumab (Herceptin) was approved for clinical use in the US in 1998. In Japan, it was approved and later became available in June, 2001. We have treated 41 patients with metastatic breast cancer with trastuzumab purchased from the US. In this paper, the details of the patients we experienced are reviewed.

Adult↗

Quantitative analysis of infantile ureteropelvic junction obstruction by diuretic renography.

Infantile hydronephrosis detected by ultrasonography poses a clinical dilemma on how to treat the condition. This article reports a retrospective study to evaluate infantile hydronephrosis due to suspected ureteropelvic junction (UPJ) obstruction by means of standardized diuretic renography and to speculate its usefulness for quantitative assessment and management of this condition. Between November 1992 and July 1999, 43 patients who had the disease detected in their fetal or infantile period were submitted to this study. Standardized diuretic renograms were obtained with 99mTc-labeled diethylene-triaminepenta-acetate (Tc-99m-DTPA) or 99mTc-labeled mercaptoacetyl triglycine (Tc-99m-MAG3) as radiopharmaceuticals. Drainage half-time clearance (T 1/2) of the activity at each region of interest set to encompass the entire kidney and the dilated pelvis was used as an index of quantitative analysis of UPJ obstruction. Initial T 1/2s of 32 kidneys with suspected UPJ obstruction were significantly longer than those of 37 without obstruction. T 1/2s of kidneys which had undergone pyeloplasty decreased promptly after surgery whereas those of units followed up without surgery decreased more sluggishly. These findings demonstrate that a standardized diuretic renographic analysis with T 1/2 can reliably assess infantile hydronephrosis with UPJ obstruction and be helpful in making a decision on surgical intervention.

Child, Preschool↗

Hepatic nodular hyperplasia in a boy with Alagille syndrome: CT and MR appearances.

A boy with Alagille syndrome complicated by hepatic nodular hyperplasia (HNH) is reported. During pre-transplantation evaluation, CT and MRI revealed a large hepatic lesion with multiple small nodular lesions. Angiography demonstrated a large hypervascular lesion and CT arterial portography (CTAP) showed a portal perfusion defect corresponding to the lesion. CTAP also revealed large portal vein branches running through the lesion. Although hepatocellular carcinoma is known to accompany Alagille syndrome, HNH should also be considered when large vessels running through the lesion are demonstrated.

Alagille Syndrome↗

A pharmacological study of the weekday-on/weekend-off oral UFT schedule in colorectal cancer patients.

PURPOSE: The new weekday-on/weekend-off schedule for oral UFT administration consists of its administration for 5 consecutive days followed by 2 days off the drug. The intratumor 5-FU (5-fluorouracil) concentration has been reported to be correlated to the tumor response in patients treated with intravenous 5-FU. The aim of this study was to investigate the pharmacokinetics during the 2 days off the drug in cancer patients treated with the weekday-on/weekend-off schedule for oral UFT. METHODS: The subjects were 24 colorectal cancer patients. They were divided into three groups, and were all given UFT, 600 mg/day, for 5 days before surgery. Surgery was performed 2, 24, or 48 h after the final dose of UFT. The 5-FU concentrations in the serum, tumor, and in the normal mucosa were measured. RESULTS: The serum 5-FU concentrations after the final dose of UFT were: 23 +/- 12 ng/ml (mean +/- SD) at 2 h, 7 +/- 3 ng/ml at 24 h, and 6 +/- 3 ng/ml at 48 h. The intratumor 5-FU concentrations were: 113 +/- 45 ng/g at 2 h, 54 +/- 20 ng/ml at 24 h, and 54 +/- 35 ng/ml at 48 h, and the concentrations in the normal mucosa were: 36 +/- 15 ng/g (mean +/- SD) at 2 h, 17 +/- 6 ng/ml at 24 h, and 18 +/- 6 ng/ml at 48 h after the final dose. While the serum 5-FU concentration decreased to very low levels by 24 h after the final dose of UFT, the intratumor 5-FU concentrations were maintained at more than 50 ng/g at least until 48 h after the final dose. The 5-FU concentrations in the normal mucosa were maintained at about one third of the intratumor concentrations at all time points. CONCLUSION: Although the weekday-on/weekend-off schedule for UFT administration included intermittent 2-day drug-off periods, this pharmacokinetic study revealed that the 5-FU concentrations in the tumor were maintained at much higher levels than in the serum throughout these periods.

Administration, Oral↗

Two mutations of the Gsalpha gene in two Japanese patients with sporadic pseudohypoparathyroidism type Ia.

Pseudohypoparathyroidism Ia (PHP-Ia), is an inherited disease with clinical hypoparathyroidism caused by parathyroid hormone resistance (PTH), and shows the phenotype of Albright hereditary osteodystrophy (AHO), including short stature, obesity, round face, brachydactyly, and subcutaneous ossification. This disease is caused by mutation that inactivates the alpha-subunit of Gs, the stimulatory regulator of adenylyl cyclase. Here, a novel frameshift mutation (delG at codon 88) in exon 4, and a missense mutation (R231H) in exon 9 of the Gsalpha gene were identified in two Japanese patients with sporadic PHP-Ia. Deletion of a G in exon 4 at codon 88 in the first patient produced a premature stop codon, resulting in the truncated protein. The second patient had a previously reported R231H mutation. Because this amino acid is located in a region, switch 2, that is thought to interact with the betagamma subunit of Gsalpha protein, this mutation may impair Gs protein function. We report here one novel Gsalpha mutation, and note that mutations in Japanese patients with PHP-Ia are probably heterogeneous.

Adult↗

Dietary restriction of choline reduces hippocampal acetylcholine release in rats: in vivo microdialysis study.

We fed rats with a diet deficient in choline for 12 weeks and studied how dietary choline deficiency affected their behavior and their ability to release acetylcholine in discrete regions of rat brain using step-through passive avoidance task and in vivo microdialysis. In comparison with the control, rats fed the choline-deficient diet showed poorer retention of nociceptive memory in the passive avoidance task. Average choline level in cerebrospinal fluid in the choline-deficient group was significantly less (33.1%) than that of control rats. In vivo microdialysis showed no difference in the pattern of acetylcholine release enhanced by intraperitoneal administration of scopolamine hydrochloride (2 mg/kg) in the striatum between the two groups, whereas in the hippocampus, the maximum and subsequent increase of acetylcholine from the baseline by scopolamine injection was significantly lower in the choline-deficient group than in the control. From the results of our study, we speculate that long-term dietary restriction of choline can affect extra- and intracellular sources of substrates required for acetylcholine synthesis, and eventually limit the ability to release acetylcholine in the hippocampus. Reduced capacity to release acetylcholine in the hippocampus implies that the mechanism, maintaining acetylcholine synthesis on increased neuronal demand, may vary in discrete regions of the brain in response to dietary manipulation. The vulnerability of the mechanism in the hippocampus to dietary choline restriction is indicated by impaired mnemonic performance we observed.

Acetylcholine↗

Capsid protein gene variation among feline calicivirus isolates.

We amplified the capsid protein gene fragments of 30 Japanese isolates of feline calicivirus (FCV), including the C, D, and E regions, by reverse transcription-polymerase chain reaction (RT-PCR), followed by direct sequencing. Alignment of the predicted amino acid sequences, together with other published sequences from the isolates obtained in other countries, demonstrated a marked heterogeneity among the isolates, confirming the current definition of hypervariable regions within the capsid protein: these regions give rise to the antigenic variations seen in FCV isolates. Phylogenetic analysis of the nucleotide sequences could not identify significant geographically or temporally separated clusters of FCV isolates, supporting the theory of a single genotype.

Amino Acid Sequence↗

Comparative study of sequential expression of the organizer-related genes in normal Cynops pyrrhogaster embryos and mesodermalized ectoderm.

An artificially mesodermalized ectoderm (mE) of early Cynops pyrrhogaster gastrula acquires the organizer property; the mE is able to induce the secondary axis. The expression of organizer-related genes was investigated during the mesodermalizing process of the mE. The expression of C. pyrrhogaster organizer-related genes, such as bra, gsc, lim-1, chd and noggin, were analyzed. Cynops pyrrhogaster shh expression was also investigated. The organizer-related genes were activated by 12 h after the mesoderm-inducing stimulus. It was noted that there was a temporal gap in the expression of each gene. The expression of bra and gsc seemed to be more quickly activated during the mesodermalizing process. While expression of lim-1 and noggin was activated later than that of bra and gsc, lim-1 expression was earlier than chd and noggin expression. Shh expression was activated later than lim-1/noggin. The present study suggests the possibility that the bra/gsc, lim-1, chd, noggin and shh genes are expressed one by one in that order during the mesodermalizing of the presumptive ectoderm. It also indicates that the sequence is not always consistent with that of the whole embryo during normal embryogenesis. The meaning of the discrepancy will be discussed in connection with the cascade of certain genes expressed during the mesodermalizing process.

Actins↗