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Biomedical subjects

Y Yasui

Publications and source records attributed to Y Yasui.

At least 19 recordsLinked to original sources
PubMed2006

Troglitazone and 9cis,11trans,13trans-conjugated linolenic acid: comparison of their antiproliferative and apoptosis-inducing effects on different colon cancer cell lines.

BACKGROUND: We have previously reported that troglitazone, a synthetic ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), and bitter gourd seed oil rich in 9cis,11trans,13trans-conjugated linolenic acid (9c,11t,13t-CLN) prevent colon carcinogenesis. To evaluate the chemotherapeutic effect and potency of these compounds on colon cancer cells, we investigated their antiproliferative and apoptosis-inducing effects using different human colon cancer cell lines. METHODS: The antiproliferative and apoptosis-inducing effects of troglitazone and 9c,11t,13t-CLN were evaluated and compared using HT-29, DLD-1 and Caco-2 cells at different stages of enterocytic differentiation. RESULTS: Troglitazone and 9c,11t,13t-CLN decreased cell viability and induced apoptosis in three colon cancer cell lines. The susceptibility of HT-29, which expresses PPARgamma at high levels, to troglitazone and 9c,11t,13t-CLN was higher than that of Caco-2 cells with low levels of PPARgamma. CONCLUSION: Troglitazone and 9c,11t,13t-CLN exhibited more effective chemotherapeutic effects on HT-29 cells than on Caco-2 cells.

Antineoplastic Agents↗
PubMed2006

Folic acid supplementation during methotrexate immunosuppression is not associated with early toxicity, risk of acute graft-versus-host disease or relapse following hematopoietic transplantation.

Methotrexate (MTX) is used as an immunosuppressive agent for acute graft-versus-host disease (GVHD) prophylaxis following hematopoietic cell transplantation (HCT). Concerns that folate intake may impair MTX effectiveness or selectively rescue leukemic cells have led to variations in clinical practice regarding supplemental folic acid during MTX administration. A retrospective, observational study was undertaken to determine the association between folic acid intake (days 0-18 post transplant) and MTX toxicity and efficacy following HCT. The study population consisted of 311 adult patients who received a myeloablative HCT for chronic myelogenous leukemia, all four scheduled doses of MTX, and did not require leucovorin rescue. Multiple linear regression models were used to assess the relationships between folic acid intake (days 0-18 post-HCT) and oral mucositis index (OMI) scores, time to engraftment and risk of detectable acute GVHD. No statistically significant differences in mean OMI scores, time to engraftment, risk of acute GVHD, days to acute GVHD, risk of relapse or survival were observed when comparing patients taking, on average, <400 (14%), 400 (58%) or >400 microg (28%) folic acid per day. Our results suggest that concurrent folic acid supplementation does not change MTX effectiveness or toxicity in this patient population.

Acute Disease↗
PubMed2006

Multiscale processing of mass spectrometry data.

This work addresses the problem of extracting signal content from protein mass spectrometry data. A multiscale decomposition of these spectra is used to focus on local scale-based structure by defining scale-specific features. Quantification of features is accompanied by an efficient method for calculating the location of features which avoids estimation of signal-to-noise ratios or bandwidths. Scale-based histograms serve as spectral-density-like functions indicating the regions of high density of features in the data. These regions provide bins within which features are quantified and compared across samples. As a preliminary step, the locations of prominent features within coarse-scale bins may be used for a crude registration of spectra. The multiscale decomposition, the scale-based feature definition, the calculation of feature locations, and subsequent quantification of features are carried out by way of a translation-invariant wavelet analysis.

Algorithms↗
PubMed2005

Metamodels of bias in Cox proportional-hazards and logistic regressions with heteroscedastic measurement error under group-level exposure assessment.

In occupational epidemiology, group-based exposure assessment entails estimating the average exposure level in a group of workers and assigning the average to all members of the group. The assigned exposure values can be used in epidemiological analyses and have been shown to produce virtually unbiased relative-risk estimates in many situations. Although the group-based exposure assessment continues to be used widely, it is unclear whether it produces unbiased relative-risk estimates in all circumstance, specifically in Cox proportional-hazards and logistic regressions when between-worker variance is not constant but proportional to the true group mean. This question is important because (i) between-worker variance has been shown to differ among exposure groups in occupational epidemiological studies and (ii) recent theoretical work has suggested that bias may exist in such situations. We conducted computer simulations of occupational epidemiological studies to address this question and analysed simulation results using 'metamodelling'. The results indicate that small-to-negligible bias can be expected to result from heteroscedastic between-worker variance. Cox proportional-hazards models can produce attenuated risk estimates, while logistic regression may result in overestimation of risk gradient. Bias caused by ignoring the heteroscedastic measurement error is unlikely to be large enough to alter the conclusion about the direction of exposure-disease association in occupational epidemiology.

Computer Simulation↗
PubMed2004

Function and quality-of-life of survivors of pelvic and lower extremity osteosarcoma and Ewing's sarcoma: the Childhood Cancer Survivor Study.

Limb-sparing surgeries have been performed more frequently than amputation based on the belief that limb-sparing surgeries provide improved function and quality-of-life (QOL). However, this has not been extensively studied in the paediatric population, which has unique characteristics that have implications for function and QOL. Using the Childhood Cancer Survivor Study, 528 adult long-term survivors of pediatric lower extremity bone tumours, diagnosed between 1970 and 1986, were contacted and completed questionnaries assessing function and QOL. Survivors were an average of 21 years from diagnosis with an average age of 35 years. Overall they reported excellent function and QOL. Compared to those who had a limb-sparing procedure, amputees were not more likely to have lower function and QOL scores and self-perception of disability included general health status, lower educational attainment, older age and female gender. Findings from this study suggest that, over time, amputees do as well as those who underwent limb-sparing surgeries between 1970 and 1986. However, female gender, lower educational attainment and older current age appear to influence function, QOL and disability.

Adolescent↗
PubMed2004

The geography of the highest mortality areas in Spain: a striking cluster in the southwestern region of the country.

AIMS: To determine the areas of Spain with the most increased mortality risk. METHODS: Age adjusted relative risk of death by gender was estimated in each of 2218 small areas of the country using a non-parametric empirical Bayes method. To determine areas with "significantly increased risk" a Poisson based score test was used. RESULTS: Mapping of the highest risk areas showed a striking geographical clustering in the southwestern region of the country. This region, comprising 8% of the Spanish population, accounts for about one third (2884 deaths) of the total excess mortality.

Cluster Analysis↗
PubMed2001

Projections from the red nucleus to the parvicellular reticular formation and the cervical spinal cord in the rat, with special reference to innervation by branching axons.

After biotinylated dextranamine injection into the dorsal part of the red nucleus (RN) in the rat, labeled axons were distributed contralaterally in the lateral tegmental field including the parvicellular reticular formation (RFp), and ipsilaterally in the medial reticular formation. In the cervical spinal cord, labeled axons were present bilaterally with a contralateral dominance mainly in laminae V-VI and the dorsal part of laminae VII. After ipsilateral injections of rhodamine dextranamine, Fluoro-ruby (FR) into the RFp and Fluoro-gold (FG) into the upper cervical spinal cord, a population of FR-labeled neurons was found in the dorsal part of the contralateral RN, whereas the majority of FG-labeled neurons were located more ventrally. However, some of them were intermingled with FR-labeled neurons, and as many as one-third of FR-labeled neurons were labeled with FG. After combined injections of FR into the RFp and FG into the lower cervical spinal cord, RN neurons labeled with FG existed more ventrally than those retrogradely labeled from the upper cervical spinal cord, and less than 10% of FR-labeled neurons were labeled with FG. The present data suggest that axon collateral innervation of the RFp and the upper cervical spinal cord by single RN neurons may be responsible for coordinating head and orofacial movements.

Animals↗
PubMed2001

Dietary effects of bitter gourd oil on blood and liver lipids of rats.

Bitter gourd is widely used as an edible plant in Asia. In this study, we evaluated the effects of bitter gourd oil (BGO) on the blood and liver lipids of rats. Three groups of rats were given a basal diet (AIN-93G) containing 7% fat by weight. The dietary fat consisted of soybean oil (control), soybean oil + BGO (6.5:0.5, w/w; 0.5% BGO), or soybean oil + BGO (5:2, w/w; 2.0% BGO). This fat treatment gave 3.4 and 15.4% of cis(c)9,trans(t)11,t13-18:3 in the dietary fat of 0.5 and 2.0% BGO, respectively. Fatty acid analysis showed the occurrence of c9,t11-18:2 in the liver of rats fed BGO diets, whereas this conjugated linoleic acid (CLA) isomer was not detected in the liver of rats fed the control diet. Furthermore, dietary BGO decreased the concentration of 18:2n-6 and increased the concentration of 22:6n-3. The formation of the CLA isomer in the liver lipids of rats fed BGO diets could be explained by either of the following two metabolic pathways, namely, enzymatic biohydrogenation of c9,t11,t13-18:3 or enzymatic isomerization of c9,c12-18:2. The BGO diets had significantly reduced free cholesterol levels with a trend toward an increase in HDL cholesterol, but there was no significant change in the total cholesterol. The dietary BGO also affected the level of plasma hydroperoxides. A slight but significant increase in hydroperoxides was found in the rats fed 2.0% BGO. This may be attributed to the lower oxidative stability of c9,t11,t13-18:3 in BGO.

Animal Nutritional Physiological Phenomena↗
PubMed2001

Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism.

This study investigated whether a polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) modifies responses to methotrexate (MTX) in patients undergoing bone marrow transplantation. About 10% to 12% of the population carry the MTHFR TT genotype (enzyme activity, 30% of wild type [CC]). Patients (n = 220) with chronic myelogenous leukemia underwent marrow allografts and were given a short course of MTX. MTX toxicity measures included the oral mucositis index (OMI), speed of engraftment (platelet and granulocyte counts), and bilirubin. Patients with lower MTHFR activity (TT genotype) had 36% higher mean OMI during days 1 to 18 (+5.7, P =.046) and 20% higher OMI between days 6 and 12 (+3.8, P =.27). Platelet counts recovered more slowly among patients with the TT genotype compared to wild type (24% slower recovery to 10 000 platelets/microL, P =.23; 34% slower to 20 000/microL, P =.08). Patients with decreased MTHFR activity appear at risk of higher MTX toxicity. Because of the high prevalence of the TT genotype, these results may have implications for MTX dosage.

Adult↗
PubMed2001

Late mortality experience in five-year survivors of childhood and adolescent cancer: the Childhood Cancer Survivor Study.

PURPOSE: Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,227 5-year survivors. PATIENTS AND METHODS: Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources and coded and categorized as recurrent disease, sequelae of cancer treatment, or non-cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data. RESULTS: The cohort, including 208,947 person-years of follow-up, demonstrated a 10.8-fold excess in overall mortality (95% confidence interval, 10.3 to 11.3). Risk of death was statistically significantly higher in females (SMR = 18.2), individuals diagnosed with cancer before the age of 5 years (SMR = 14.0), and those with an initial diagnosis of leukemia (SMR = 15.5) or CNS tumor (SMR = 15.7). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 67% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 19.4), along with cardiac (SMR = 8.2), pulmonary (SMR = 9.2), and other causes (SMR = 3.3). Treatment-related associations were present for subsequent cancer mortality (radiation, alkylating agents, epipodophyllotoxins), cardiac mortality (chest irradiation, bleomycin), and other deaths (radiation, anthracyclines). No excess mortality was observed for external causes (SMR = 0.8). CONCLUSION: While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.

Adolescent↗
PubMed2001

Organization of projections from the medial agranular cortex to the superior colliculus in the rat: a study using anterograde and retrograde tracing methods.

The organization of corticotectal projections from the medial agranular cortex (AGm), which has been considered to contain rat's frontal eye field, was examined using anterograde and retrograde tracing techniques. When biotinylated dextranamine (BDA) injections were made into the rostral part of the AGm, small numbers of BDA-labeled axons were found in the rostral two-thirds of the superior colliculus (SC) while some labeled axons were seen in the caudal one-third of the SC. These labeled axons were distributed mainly in the lateral part of the stratum griseum intermediale. On the other hand, after BDA injections into the caudal part of the AGm, moderate to dense plexuses of labeled axons were found in the rostral two-thirds of the SC while some labeled axons were seen in the caudal one-third of the SC. These labeled axons were distributed in the ventromedial and dorsolateral marginal zones of the stratum griseum intermediale as well as in the stratum griseum profundum. The corticotectal projections were largely uncrossed. After combined injections of BDA into the caudal part of the AGm on one side and cholera toxin B subunit (CTb) into the paramedian pontine reticular formation on the opposite side or into the interstitial nucleus of Cajal on the same side, the overlapping distributions of BDA-labeled axons and CTb-labeled neurons were found in the ventromedial marginal zone of the stratum griseum intermediale ipsilateral to the site of BDA injection. These results suggest that the caudal part of the AGm plays a more significant role in the oculomotor function than does the rostral part of the AGm.

Animals↗
PubMed2001

Protein kinases required for segregation of vimentin filaments in mitotic process.

Vimentin, one of type III intermediate filament (IF) proteins, is expressed not only in mesenchymal cells but also in most types of tumor cells. In the present study, we introduced several types of vimentin mutated at putative phosphorylation sites in its amino-terminal head domain into type III IF-negative T24 cells. Site-specific mutation induced the formation of an unusually long bridge-like IF structure between the unseparated daughter cells, although these mutants formed the filament network similar to wild type in interphase cells. Together with sites phosphorylated by Rho-kinase and protein kinase C (PKC), vimentin-Ser72, which can not be phosphorylated by any known vimentin kinase, was one of the mutation sites essential for this phenotype. We further demonstrated that vimentin-Ser72 was phosphorylated specifically at the cleavage furrow during cytokinesis. These observations suggest the existence of a novel protein kinase responsible for vimentin filament separation through the cleavage furrow-specific vimentin phosphorylation. We propose that Rho-kinase, PKC, and an unidentified vimentin-Ser72 kinase may play important roles in vimentin filament separation during cytokinesis.

Actin Cytoskeleton↗
PubMed2001

Second malignant neoplasms in five-year survivors of childhood cancer: childhood cancer survivor study.

BACKGROUND: Because survival rates among childhood cancer patients are increasing, assessing the risk of second and subsequent malignant neoplasms (SMNs) is ever more important. Using the Childhood Cancer Survivor Study cohort, we identified the risk of SMNS: METHODS: A retrospective cohort of 13 581 children diagnosed with common cancers before age 21 years and surviving at least 5 years was constructed with the use of data from patients treated at 25 U.S. and Canadian institutions. SMNs were ascertained through self-administered questionnaires and verified by pathology reports. Information on therapeutic exposures was abstracted from medical records. The risk of SMN was evaluated by standardized incidence ratios (SIRs) and excess absolute risk. Poisson multiple regression models were used to assess the impact of host and therapy factors on the risk of developing SMNS: All statistical tests were two-sided. RESULTS: In 298 individuals, 314 SMNs were identified (SIR = 6.38; 95% confidence interval [CI] = 5.69 to 7.13). The largest observed excess SMNs were bone and breast cancers (SIR = 19.14 [95% CI = 12.72 to 27.67] and SIR = 16.18 [95% CI = 12.35 to 20.83], respectively). A statistically significant excess of SMNs followed all childhood cancers. In multivariate regression models adjusted for therapeutic radiation exposure, SMNs of any type were independently associated with female sex (P<.001), childhood cancer at a younger age (P for trend <.001), childhood Hodgkin's disease or soft-tissue sarcoma (P<.001 and P =.01, respectively), and exposure to alkylating agents (P for trend =.02). Twenty years after the childhood cancer diagnosis, the cumulative estimated SMN incidence was 3.2%. However, only 1.88 excess malignancies occurred per 1000 years of patient follow-up. CONCLUSIONS: Success in treating children with cancer should not be overshadowed by the incidence of SMNS: However, patients and health-care providers must be aware of risk factors for SMNs so that surveillance is focused and early prevention strategies are implemented.

Adolescent↗
PubMed2001

An increase in circulating mast cell colony-forming cells in asthma.

We compared a potential to generate mast cells among various sources of CD34(+) peripheral blood (PB) cells in the presence of stem cell factor (SCF) with or without thrombopoietin (TPO), using a serum-deprived liquid culture system. From the time course of relative numbers of tryptase-positive and chymase-positive cells in the cultured cells grown by CD34(+) PB cells of nonasthmatic healthy individuals treated with G-CSF, TPO appears to potentiate the SCF-dependent growth of mast cells without influencing the differentiation into mast cell lineage. CD34(+) PB cells from asthmatic patients in a stable condition generated significantly more mast cells under stimulation with SCF alone or SCF+TPO at 6 wk of culture than did steady-state CD34(+) PB cells of normal controls. Single-cell culture studies showed a substantial difference in the number of SCF-responsive or SCF+TPO-responsive mast cell progenitors in CD34(+) PB cells between the two groups. In the presence of TPO, CD34(+) PB cells from asthmatic children could respond to a suboptimal concentration of SCF to a greater extent, compared with the values obtained by those of normal controls. Six-week cultured mast cells of asthmatic subjects had maturation properties (intracellular histamine content and tryptase/chymase enzymatic activities) similar to those derived from mobilized CD34(+) PB cells of nonasthmatic subjects. An increase in a potential of circulating hemopoietic progenitors to differentiate into mast cell lineage may contribute to the recruitment of mast cells toward sites of asthmatic mucosal inflammation.

Adolescent↗
PubMed2001

Multi-beam polarized photometric detector for high-performance liquid chromatography.

A novel multi-beam polarized photometric detector (PPD) for high-performance liquid chromatography (HPLC) is described. By pairing a polarizing prism with a thin quartz plate as a retarder, many linear polarized beams are produced at every 1/2 wavelength of the plate, and the polarizing axes of the adjacent beams intersect each other. The addition of another prism inclining its polarizing axis by pi/4 against the first one enables the simultaneous measurement of optical rotations based on the PPD at many wavelengths. The combination of these optics with a photo-diode array detector can be used to construct a modulated type polarimeter. This detector is designed to measure the optical rotation of an analyte at its absorption band. The spline function connecting the points at 1/4 wavelengths of the plate was used as a baseline to extract the PPD waves. The use of the similarity factor as a noise filter gave high sensitivity. Application of the proposed technique to an analyte carrying the Cotton absorption band provided good results.

Chromatography, High Pressure Liquid↗
PubMed2001

Women's interest in genetic testing for breast cancer susceptibility may be based on unrealistic expectations.

We report on results of an interview study assessing women's attitudes toward and hypothetical interest in genetic susceptibility testing for breast cancer. Data are from 246 interviews with women of varying ethnicity (African American, European American, Native American, and Ashkenazi Jewish), family history of breast cancer (negative, positive, and borderline), and educational level. Semistructured interviews included questions on general health beliefs; attitudes, experiences, and concerns about breast cancer; and hypothetical interest in genetic testing. Influence of specific test characteristics was assessed with 14 Likert scales varying negative and positive predictive value, timing of disease, possible medical interventions following a positive result. Results reported include both statistical and qualitative analysis. We found that women had a high level of interest in testing which, in general, did not vary by ethnicity, level of education, or family history. Interest in testing appeared to be shaped by an exaggerated sense of vulnerability to breast cancer, limited knowledge about genetic susceptibility testing, and generally positive views about information provided through medical screening. However, study participants were most interested in a test that didn't exist (high positive predictive value followed by effective, noninvasive, preventive therapy) and least interested in the test that does exist (less than certain positive predictive value, low negative predictive value, and limited, invasive, and objectionable therapeutic options). Our data suggest that without a careful counseling process, women could easily be motivated toward interest in a test which will not lead to the disease prevention they are seeking.

Attitude to Health↗