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Hiroshi Saito

Publications and source records attributed to Hiroshi Saito.

At least 19 recordsLinked to original sources
PubMed2007

Latency of vestibular responses of pursuit neurons in the caudal frontal eye fields to whole body rotation.

The smooth pursuit system and the vestibular system interact to keep the retinal target image on the fovea by matching the eye velocity in space to target velocity during head and/or whole body movement. The caudal part of the frontal eye fields (FEF) in the fundus of the arcuate sulcus contains pursuit-related neurons and the majority of them respond to vestibular stimulation induced by whole body movement. To understand the role of FEF pursuit neurons in the interaction of vestibular and pursuit signals, we examined the latency and time course of discharge modulation to horizontal whole body rotation during different vestibular task conditions in head-stabilized monkeys. Pursuit neurons with horizontal preferred directions were selected, and they were classified either as gaze-velocity neurons or eye/head-velocity neurons based on the previous criteria. Responses of these neurons to whole body step-rotation at 20 degrees/s were examined during cancellation of the vestibulo-ocular reflex (VOR), VOR x1, and during chair steps in complete darkness without a target (VORd). The majority of pursuit neurons tested (approximately 70%) responded during VORd with latencies <80 ms. These initial responses were basically similar in the three vestibular task conditions. The shortest latency was 20 ms and the modal value was 24 ms. These responses were also similar between gaze-velocity neurons and eye/head-velocity neurons, indicating that the initial responses (<80 ms) were vestibular responses induced by semicircular canal inputs. During VOR cancellation and x1, discharge of the two groups of neurons diverged at approximately 90 ms following the onset of chair rotation, consistent with the latencies associated with smooth pursuit. The shortest latency to the onset of target motion during smooth pursuit was 80 ms and the modal value was 95 ms. The time course of discharge rate difference of the two groups of neurons between VOR cancellation and x1 was predicted by the discharge modulation associated with smooth pursuit. These results provide further support for the involvement of the caudal FEF in integration of vestibular inputs and pursuit signals.

Animals↗
PubMed2006

Further synthetic and biological studies on vitamin D hormone antagonists based on C24-alkylation and C2alpha-functionalization of 25-dehydro-1alpha-hydroxyvitamin D(3)-26,23-lactones.

An efficient synthesis and the biological evaluation of 80 novel analogs of 25-dehydro-1alpha-hydroxyvitamin D3-26,23S-lactone 2 (TEI-9647) and its 23R epimer (3) in which the lactone ring was systematically functionalized by introduction of a C1 to C4 primary alkyl group at the C24 position (5 sets of 4 diastereomers), together with their C2alpha-methyl, 3-hydroxypropyl, and 3-hydroxypropoxy-substituted derivatives were described. The triene structure of the vitamin D3 was constructed using palladium-catalyzed alkenylative cyclization of the A-ring precursor enyne with the CD-ring counterpart bromoolefin having the C24-alkylated lactone moiety on the side chain. The CD-ring precursors having 23,24-cis lactones were prepared by using a chromium-mediated syn-selective allylation-lactonization process, and the 23,24-trans lactone derivatives were derived from these via inversion of the C23 stereochemistry. The biological evaluation revealed that both binding affinity for chick vitamin D hormone receptor and antagonistic activity (inhibition of vitamin D hormone induced HL-60 cell differentiation) were affected by the orientation and chain-length of the primary alkyl group on the lactone ring. Furthermore, the C2alpha-functionalization of the C24-alkylated vitamin D3 lactones dramatically enhanced their biological activities. The most potent compound to emerge, (23S,24S)-2alpha-(3-hydroxypropoxy)-24-propyl exhibited almost 1000-fold stronger antagonistic activity (IC50=7.4 pM) than 2 (IC50=6.3 nM).

Alkylation↗
PubMed2006

Chemokine system and tissue infiltration in aggressive NK-cell leukemia.

NK cell-type lymphoproliferative disease of granular lymphocytes can be subdivided into aggressive NK-cell leukemia (ANKL) and chronic NK-cell lymphocytosis (CNKL). Hepatosplenomegaly is observed in ANKL patients, and hepatic failure is a common cause of death. Significant numbers of ANKL cells were pathologically observed in sinusoidal and interlobular regions of the liver, and in the splenic red pulp. In our previous study, ANKL cells were simultaneously positive for CXCR1 and CCR5. So, in order to elucidate the mechanism in the systemic migration of ANKL cells, we investigated the expression of the corresponding chemokines in ANKL compared with CNKL. The serum level of IL-8, MIP-1alpha and MIP-1beta was significantly elevated in ANKL patients, and ANKL cells were highly positive for IL-8, RANTES, MIP-1alpha and MIP-1beta according to intracellular staining and RT-PCR. These chemokines were also positively stained in hepatocytes. The interaction between Fas and Fas ligand (FasL) is supposed to be one of the mechanisms for liver dysfunction in ANKL. The serum concentration of soluble FasL was significantly high in ANKL patients, and ANKL cells expressed FasL protein in the cytoplasm. These results suggest that the chemokine system plays an important role in the transmigration of FasL-expressing ANKL cells.

Chemokines↗
PubMed2006

Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902.

PURPOSE: We initially conducted a randomized phase II study to compare irinotecan and cisplatin (IP) versus irinotecan, cisplatin, and etoposide (IPE) after etoposide and cisplatin (EP) with concurrent twice-daily thoracic radiotherapy (TRT) in limited-disease small-cell lung cancer (LD-SCLC). We amended the protocol to evaluate IP after EP with concurrent twice-daily TRT in a single-arm phase II study because of an unacceptable toxicity in IPE. PATIENTS AND METHODS: Previously untreated patients with LD-SCLC were treated intravenously with etoposide 100 mg/m2 on days 1 through 3 and cisplatin 80 mg/m2 on day 1 with concurrent twice-daily TRT (1.5 Gy per fraction, a total dose of 45 Gy) beginning on day 2 followed by three cycles of irinotecan 60 mg/m2 on days 1, 8, and 15 and cisplatin 60 mg/m2 on day 1 of a 4-week cycle. RESULTS: Of the 51 patients enrolled, 49 patients were assessable for response and toxicity. The overall response rate and complete response rate were 88% and 41%, respectively. The median survival time for all patients was 23 months. The 2-year and 3-year survival rates were 49% and 29.7%, respectively. The median progression-free survival was 11.8 months. The major toxicities observed were neutropenia (grade 4, 84%), febrile neutropenia (grade 3, 31%), infection (grade 3 to 4, 33%), electrolytes imbalance (grade 3 to 4, 20%), and diarrhea (grade 3 to 4, 14%). CONCLUSION: EP with concurrent twice-daily TRT followed by the consolidation of IP appears to be an active regimen which deserves further phase III testing in patients with LD-SCLC.

Aged↗
PubMed2006

Negative association of obesity and its related chronic inflammation with serum glycated albumin but not glycated hemoglobin levels.

BACKGROUND: Measurements of glycated albumin (GA) as well as glycated hemoglobin (HbA1c) have been applied in order to monitor chronic glycemic control in diabetic patients. Both glycated proteins are known influenced by various factors other than glycemia. It has recently been reported that GA level is low in obese, non-diabetic children and is negatively associated with body mass index (BMI) in adult diabetic patients. However, the reasons for the connection between obesity and GA remain unknown. The aim of this study was to examine whether BMI and the obesity-related inflammatory marker plasma high-sensitivity C-reactive protein (hs-CRP) are independently associated with GA and HbA1c. METHODS: Two hundred and twelve non-diabetic subjects (158 with normal glucose tolerance and 54 with impaired glucose tolerance) were enrolled in this study. The effects of fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2-h glucose, age, BMI and hs-CRP on HbA1c as well as those on GA were analyzed. RESULTS: FPG significantly correlated with HbA1c, and also significantly but weakly correlated with GA. BMI showed a significantly positive correlation with HbA1c, whereas it negatively correlated with GA. Plasma hs-CRP showed a weak positive correlation with HbA1c, whereas it was negatively associated with GA. By stepwise multivariate regression analyses, BMI and hs-CRP were negatively associated with GA but not with HbA1c. CONCLUSIONS: These results demonstrated that BMI as well as hs-CRP were independent negative risks of GA but not of HbA1c in non-diabetic subjects. Obesity and its related chronic inflammation are involved in lower serum GA levels, but not HbA1c levels, in relation to glycemia.

Body Mass Index↗
PubMed2006

Comparison of observed and expected numbers of detected cancers in the research center for cancer prevention and screening program.

BACKGROUND: The Research Center for Cancer Prevention and Screening program is a one-arm prospective study designed to evaluate the effect of multiple modalities for cancer screening. Basic programs consist of screening tests for cancer of the lung, esophagus, stomach, colon, rectum, liver, gall bladder, pancreas and kidneys, in addition to prostate cancer screening for males and breast, cervical, endometrial and ovarian cancer screenings for females. OBJECTIVE: To investigate the possibility of overdiagnosis, we compared the observed numbers with expected numbers based on the model. METHODS: We calculated the expected number of cancers on the basis of negative or positive history of screening tests within the previous year, based on assumed sensitivity and sojourn time. Observed numbers of screen-detected cases for stomach, colorectal, lung, prostate and breast cancer were compared with expected numbers. RESULTS: From February 2004 to January 2005, 3786 participants were enrolled in our study. The overall cancer detection rate was 5.8% (119/2061) for males and 4.1% (71/1725) for females. No statistically significant difference was found between observed and expected cases for colorectal cancer screening, gastric cancer screening for females and lung cancer screening for males. Observed numbers of breast, prostate and lung cancer for females exceeded those expected (P < 0.05). CONCLUSIONS: Although cancer screening programs in the present study increased the detection of potentially curable cancers, these modalities, particularly lung, breast and prostate screening, might detect cancers which would not necessarily be clinically significant. We should therefore weigh up benefit and harm for such cancer screening programs.

Adult↗
PubMed2006

Body mass index negatively influences glycated albumin, but not glycated hemoglobin, in diabetic patients.

Measurement of serum glycated albumin (GA) is accepted as an alternative method to evaluate chronic glycemic control in diabetic patients in whom measurement of HbA 1c is inadequate for some reason. Although GA levels are known to be influenced by serum albumin turnover besides glycemia, little is known about the physiological and pathological conditions affecting GA levels. This study was aimed to prove the effects of body mass index (BMI) on GA measurement in diabetic patients. We studied 209 patients with type 2 diabetes mellitus whose HbA 1c levels had been stable for at least the past three months. In the study patients HbA 1c and GA levels were found to be correlated to one another. Fasting plasma glucose (FPG) was significantly correlated with HbA 1c and GA. BMI showed a significant negative correlation with GA levels, whereas there was no correlation of BMI with HbA 1c levels. Multivariate regression analyses revealed that only FPG was positively correlated with HbA 1c, while FPG was positively and BMI was negatively correlated with GA. Only BMI was negatively correlated with the ratio of GA to HbA 1c. These results clearly demonstrate that GA levels are negatively influenced by BMI in diabetic patients.

Adult↗
PubMed2006

Cell bioassay for paralytic shellfish poisoning (PSP): comparison with postcolumn derivatization liquid chromatographic analysis and application to the monitoring of PSP in shellfish.

We performed a neuroblastoma cell (Neuro2a) culture assay modified slightly from a method reported previously to provide a simple and sensitive evaluation of paralytic shellfish poisoning (PSP) toxicity in shellfish. The cell bioassay was just as sensitive for C-toxins as for gonyautoxins. The sensitivity of our cell bioassay was 4 times that of the current standard mouse bioassay. Using the cell bioassay, we evaluated PSP toxicity in 361 shellfish samples collected from Mikawa Bay and Ise Bay, Aichi Prefecture, Japan, from April 1999-March 2002. The results were compared with those obtained in a postcolumn derivatization liquid chromatographic analysis. PSP toxins were detected in 236/361 samples by both assays, and there was a fairly good correlation (r = 0.9001, n = 236, p < 0.001) between the results from the two assays. We applied this cell bioassay when short-necked clams in the bay turned poisonous in 2001. The chronological changes in PSP toxicity in the short-necked clams were analyzed and compared with those of the cell density of poisonous plankton (Alexandrium tamarense) occurring in the bay. The PSP toxicity in shellfish peaked 2 weeks after the cell density reached a maximum. We recommend using the cell bioassay for routine monitoring of PSP toxicity in shellfish living in natural marine environments.

Animals↗
PubMed2006

A case of dysferlinopathy presenting choreic movements.

Mutations in the dysferlin gene cause limb-girdle muscular dystrophy type 2B (LGMD2B). The involvement of the central nervous system in dysferlinopathy has not been described. We describe the clinical features of a patient with LGMD2B associated with dysferlin mutations (homozygous G3370T) who presented progressive choreic movements. The patient had no evidence of other causes of chorea. It is suggested that the chorea may be associated with the altered expression of the brain isoform of dysferlin.

Brain↗
PubMed2006

Serum triglycerides and colorectal adenoma in a case-control study among cancer screening examinees (Japan).

OBJECTIVE: Most epidemiologic studies have shown serum triglycerides to be associated with colorectal adenoma. However, whether the association can be modified by smoking is unknown. We cross-sectionally investigated the association of serum triglycerides with the risk of adenoma by smoking status. METHODS: We identified 782 newly diagnosed adenoma cases from the examinees of a colorectal cancer screening program. All cases were diagnosed by a magnifying colonoscopy with dye spreading. We determined 738 controls without present illness or past history of adenoma from among the examinees. They provided their lifestyle information and fasting blood samples to measure their serum triglycerides. We calculated odds ratios (OR) and 95% confidence intervals (CI) of colorectal adenoma for serum triglycerides. RESULTS: High serum triglycerides were associated with colorectal adenoma (OR 1.5; 95% CI 1.1-2.0 for the highest versus the lowest quartile, P (trend, )0.030). A stronger association was observed between three or more adenoma cases and study controls (OR 2.3; 95% CI 1.3-4.2, P (trend,) < 0.0010). After classifying the study subjects by smoking status, a significant linear risk trend was found in ever-smokers (P (trend), 0.0018) but not in never-smokers (P (trend), 0.94; P (interaction), 0.067). CONCLUSIONS: Our results suggested that a higher serum triglyceride level may be related to a larger number of adenomas. Adenoma development involving an elevated serum triglyceride level may be modified by smoking.

Adenoma↗
PubMed2006

Phase II study of 3-week scheduling of irinotecan in combination with cisplatin in patients with advanced nonsmall-cell lung cancer.

OBJECTIVES: The combination of irinotecan and cisplatin given every 4 weeks is one of the standard treatments for advanced nonsmall-cell lung cancer (NSCLC) in Japan. The purpose of this study is to evaluate the efficacy, safety and dose-intensity as a measure of the feasibility of 3-week scheduling of irinotecan and cisplatin in patients with advanced NSCLC in phase II study. METHODS: Previously untreated patients with stage IIIB and IV NSCLC were treated intravenously with irinotecan (60 mg/m2) on days 1 and 8 and cisplatin (60 mg/m2) on day 1 of a 3-week cycle. RESULTS: Of the 28 patients enrolled, 27 were evaluable for response and toxicity. The response rate was 30% (95% confidence interval, 14-50%). The median duration of response was 16 weeks (range, 10-26 weeks). The median survival time for all patients was 52 weeks and the 1-year and 2-year survival rates were 48% and 29%, respectively. The dose-intensity of irinotecan was 34 mg/m2/wk (range, 19-40). The major toxicities observed were neutropenia (grade 3, 30%; 4, 30%), leukopenia (grade 3, 30%), and diarrhea (grade 3, 22%). Other toxicities were generally mild. CONCLUSIONS: Three-week scheduling of irinotecan and cisplatin is effective and feasible in advanced NSCLC.

Adult↗
PubMed2006

Molecular characterization of two anther-specific genes encoding putative RNA-binding proteins, AtRBP45s, in Arabidopsis thaliana.

RRM (RNA-recognition motif) domain is important for the post-transcriptional regulation of gene expression including RNA processing. In our previous study, we found one anther- and/or pollen-specific gene (LjRRM1, previously named as LjMfb-U93) in model legume, Lotus japonicus. Because of the richness of genomic information of another model plant, Arabidopsis thaliana, for functional analysis, we identified and characterized the orthologous genes in A. thaliana. By comparison of the partial nucleotide sequence of LjRRM1 to the public database, we identified three homologous genes (AtRBP45a, AtRBP45b, and AtRBP45c) in A. thaliana genome. Based on promoter analysis, both AtRBP45a and AtRBP45c were specifically expressed in immature anther tissues (tapetum cells) and mature pollen grains of transgenic plants. This expression pattern of AtRBP45a and AtRBP45c is quite similar to that of LjRRM1, indicating that AtRBP45a and AtRBP45c would be orthologous to LjRRM1. Because in another previous experiment, it was shown that proteins having RRM domains were related to pre-mRNA maturation, and as a conclusion, it is possible that LjRRM1, AtRBP45a, and AtRBP45c genes encoding RNA-binding proteins are functionally involved in the repression of translation in mature pollen grains in L. japonicus and A. thaliana.

Amino Acid Sequence↗
PubMed2006

Anther-specific genes, which expressed through microsporogenesis, are temporally and spatially regulated in model legume, Lotus japonicus.

Pollen germination and pollen tube elongation are important for pollination and fertilization in higher plants. To date, several pollen-specific genes have been isolated and characterized. However, there is little information about the precise spatial and temporal expression pattern of pollen-specific genes in higher plants. In our previous study, we identified 132 anther-specific genes in the model legume Lotus japonicus by using cDNA microarray analysis, though their precise expression sites in the anther tissues were not determined. In this study, by using in situ hybridization experiments, we determined the spatial and temporal expression sites of 46 anther-specific genes (ca. 35%), which were derived from two groups, cluster I-a and cluster II-a, according to flower developmental stages. In the case of the genes grouped into cluster I-a, thirteen clones were characterized. The specific hybridized signals were varied among the clones, and were observed in tapetum cells, microspores, and anther walls at the early developmental stage of anther tissues. In the case of the genes classified into cluster II-a, we used thirty three different cDNA clones encoding primary and secondary metabolism-related proteins, cell wall reconstruction-related proteins, actin reorganization-related proteins, and sugar transport-related proteins, etc., as a probe. Interestingly, all genes in these thirty three clones examined were specifically expressed in the bicellular pollen grains, though the signal intensity was varied among clones. From the data of the cluster II-a genes, the mRNAs related to pollen germination and pollen tube elongation were specifically transcribed and preserved in mature pollen grains.

Gene Expression Regulation, Plant↗
PubMed2006

Traumatic pseudoaneurysm of the subclavian artery following anterior dislocation of the shoulder: a report of a surgical case.

Vascular complications associated with simple anterior dislocation of the shoulder joint are rare. We report on a patient with a pseudoaneurysm of the right subclavian artery following anterior dislocation of the right shoulder. Complaints of progressive neurological deficit and swelling in the right upper extremity were initially attributed to hemarthrosis of the right shoulder joint, but pseudoaneurysm of the right subclavian artery was identified during an emergent operation on the right shoulder. Uncontrollable arterial hemorrhaging from the skin incision erupted during the operation and was treated using a double surgical approach.

Accidental Falls↗
PubMed2006

[Vitamin D and cancer].

Vitamin D is a steroid hormone which regulates calcium and bone homeostasis through intestine, bone, kidney and parathyroid. It has been reported that vitamin D inhibits the cancer incidence and tumor growth. In this review, we summarize the epidemiological, animal and clinical research of vitamin D on breast, colon and prostate cancer.

Animals↗
PubMed2006

Colorectal cancer screening using immunochemical faecal occult blood testing in Japan.

Japan has had a programme of colorectal cancer screening with immunochemical faecal occult blood testing since 1992. Participation rates are around 17%. Approximately 7% of subjects test positive and, of these, around 60% comply with the request to undergo further diagnostic testing. Colorectal cancer rates have been increasing rapidly in Japan in recent decades, and there is an urgent need to improve participation rates.

Adult↗