Search PubMed⌕ Search

Biomedical subjects

S Fukuhara

Publications and source records attributed to S Fukuhara.

At least 109 records · Page 6Linked to original sources
PubMed1998

Refinement of the BCL2/immunoglobulin heavy chain fusion gene in t(14;18)(q32;q21) by polymerase chain reaction amplification for long targets.

The t(14;18)(q32;q21) translocation, involving the BCL2 gene and junctional segments (JH) of the immunoglobulin heavy chain gene (IGH), constitutes the most common chromosomal translocation in non-Hodgkin's lymphoma of B-cell type. Although the breakpoints in BCL2 are largely clustered within the major breakpoint region (MBR) and minor cluster region (mcr), it is known that some breakpoints map away from these regions, resulting in negative amplification of the junctional sequence by polymerase chain reaction (PCR) for < 1 kb targets. To circumvent this problem, we applied a novel PCR technology for long DNA targets, long-distance (LD-) PCR, to the detection of t(14;18) in clinical materials. Oligonucleotide primers were designed to be quite distant from the two known cluster regions in BCL2, and those for the corresponding IGH were complementary to the enhancer and constant regions. In all 52 cases identified as carrying BCL2/JH fusion by conventional Southern blot analysis, LD-PCR successfully amplified fragments encompassing the junctions, which were readily identifiable on ethidium bromide-stained gel. The size of the LD-PCR products ranged from 3.9 kb to 10.7 kb in MBR/IGH fusion and 1.9 kb to 16 kb in mcr/IGH fusion. Furthermore, we established an LD-PCR protocol for > 20 kb targets, which covered the intervening region between the MBR and mcr. Restriction analysis of the LD-PCR products revealed that breakpoints in 33 cases fell within the 150 bp-MBR region, and in 3 cases were within the mcr determined previously by others. In contrast, the breakpoints of the remaining 16 cases were distributed over a large region from the MBR through mcr. Nucleotide sequence analysis of a potential cluster region revealed the presence of an Alu repeat sequence. Restriction analysis of LD-PCR products with BstEII demonstrated a predominant usage of the JH6 segment (71%) at the BCL2/JH junctions. LD-PCR using primers for the constant region genes showed that class switch recombination occurred in more than 80% of the IGH genes on the der(14) chromosome. Our study showed that LD-PCR was capable of detecting virtually any t(14;18) that occurred within the approximately 30 kb region downstream of the MBR, and thus is suitable for initial diagnosis of lymphoma tissues. Furthermore, as amplified fragments obtained by the LD-PCR contained distinctive regions of BCL2 and IGH, restriction analysis and nucleotide sequencing of the products refined the characteristics of t(14;18).

Base Sequence↗
PubMed1998

Changes of immunological markers after autologous peripheral blood stem cell transplantation.

PURPOSE: Recently high-dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) has become an important treatment for hematological and solid tumors. METHODS: Immunological parameters were examined before and after PBSCT in 9 patients with lung cancer and 13 patients with malignant lymphoma. Findings were compared with those for bone marrow transplantation (BMT). Peripheral blood cells were analyzed for phenotype and the levels of cytokines and soluble factors were measured. RESULTS: After PBSCT, activated T cells (CD3+HLA-DR+ cells, CD8+HLA-DR+ cells) and suppressor/cytotoxic T cells (CD8+CD11b- cells) were significantly higher in the patients with lung cancer than in those with malignant lymphoma. Serum levels of interleukin-4 and soluble interleukin-2 receptor were also significantly higher in the patients with lung cancer than in those with lymphoma. On the other hand, the serum levels of interferon gamma, tumor necrosis factor alpha, interleukin-6, soluble human leukocyte antigen class 1, and soluble thrombomodulin were significantly increased after bone marrow transplantation. The transfused peripheral stem cells of lung cancer and lymphoma patients had a similar number of granulocyte/macrophage-colony-forming units, but lung cancer patients had significantly more CD34-positive cells. CONCLUSION: By reinfusing large numbers of autologous immune cells, PBSCT may accelerate immune reconstitution, with T cells being likely to have a marked therapeutic potential. The changes after PBSCT were greater in patients with lung cancer than in lymphoma patients. These blood cells are potent mediators of anticancer activity and could play an important role in the elimination of autologous malignant cells.

Adult↗
PubMed1998

Signaling pathways via NK1 receptors and their desensitization in an AR42J cell line.

Substance P (SP) has been shown to induce phosphatidylinositol (PI) hydrolysis and Ca2+ mobilization in AR42J cells. In this study, we confirmed the expression of NK1 but not NK2 or NK3 receptors in this cell line, and further investigated signaling pathways via NK1 receptors and their desensitization. The activation of NK1 receptors by SP affected neither basal cyclic AMP level nor cyclic AMP accumulation induced by secretin and forskolin, although it stimulated PI hydrolysis. Furthermore, SP induced Ca2+ mobilization even in the absence of extracellular Ca2+, though maximal response was reduced. U73122, a phospholipase C (PLC) inhibitor, nearly abolished Ca2+ response to SP. In addition, SP-induced Ca2+ signaling and PI hydrolysis rapidly desensitized following short exposure to SP, which did not affect the Ca2+ amount in intracellular Ca2+ stores or Ca2+ responses to carbachol and gastrin releasing peptide-10. These findings suggested that NK1 receptors do not couple to adenylate cyclase, although they induce PI response, and that NK1 receptors induce both intracellular Ca2+ release and Ca2+ influx through PLC activation. Ca2+ signaling and PI hydrolysis through NK1 receptors desensitized rapidly after the stimulation, maybe dependent on the modification of NK1 receptors.

Animals↗
PubMed1998

Translating health status questionnaires and evaluating their quality: the IQOLA Project approach. International Quality of Life Assessment.

This article describes the methods adopted by the International Quality of Life Assessment (IQOLA) project to translate the SF-36 Health Survey. Translation methods included the production of forward and backward translations, use of difficulty and quality ratings, pilot testing, and cross-cultural comparison of the translation work. Experience to date suggests that the SF-36 can be adapted for use in other countries with relatively minor changes to the content of the form, providing support for the use of these translations in multinational clinical trials and other studies. The most difficult items to translate were physical functioning items, which used examples of activities and distances that are not common outside of the United States; items that used colloquial expressions such as pep or blue; and the social functioning items. Quality ratings were uniformly high across countries. While the IQOLA approach to translation and validation was developed for use with the SF-36, it is applicable to other translation efforts.

Cross-Cultural Comparison↗
PubMed1998

Cross-cultural comparisons of the content of SF-36 translations across 10 countries: results from the IQOLA Project. International Quality of Life Assessment.

Increasingly, translated and culturally adapted health-related quality of life measures are being used in cross-cultural research. To assess comparability of results, researchers need to know the comparability of the content of the questionnaires used in different countries. Based on an item-by-item discussion among International Quality of Life Assessment (IQOLA) investigators of the content of the translated versions of the SF-36 in 10 countries, we discuss the difficulties that arose in translating the SF-36. We also review the solutions identified by IQOLA investigators to translate items and response choices so that they are appropriate within each country as well as comparable across countries. We relate problems and solutions to ratings of difficulty and conceptual equivalence for each item. The most difficult items to translate were physical functioning items that refer to activities not common outside the United States and items that use colloquial expressions in the source version. Identifying the origin of the source items, their meaning to American English-speaking respondents and American English synonyms, in response to country-specific translation issues, greatly helped the translation process. This comparison of the content of translated SF-36 items suggests that the translations are culturally appropriate and comparable in their content.

Cross-Cultural Comparison↗
PubMed1998

Testing the equivalence of translations of widely used response choice labels: results from the IQOLA Project. International Quality of Life Assessment.

The similarity in meaning assigned to response choice labels from the SF-36 Health Survey (SF-36) was evaluated across countries. Convenience samples of judges (range, 10 to 117; median = 48) from 13 countries rated translations of response choice labels, using a variation of the Thurstone method of equal appearing intervals. Judges marked a point on a 10-cm line-representing the magnitude of a response choice label (e.g., "good" relative to the anchors of "poor" and "excellent"). Ratings were evaluated to determine the ordinal consistency of response choice labels within a response scale; the degree to which differences between adjacent response choice labels were equal interval; and the amount of variance due to response choice label, country, judge, and interaction between response choice label and country. Results confirmed the hypothesized ordering of response choice labels; the percentage of ordinal pairs ranged from 88.7% to 100% (median = 98.2%) across countries and response scales. Examination of the average magnitudes of response choice labels supported the "quasi-interval" nature of the scales. Analysis of variance (ANOVA) results supported the generalizability of response choice magnitudes across countries; labels explained 64% to 77% of the variance in ratings, and country explained 1% to 3%. These results support the equivalence of SF-36 response choice labels across countries. Departures from the assumption of equal intervals, when observed, were similar across countries and were greatest for the two response scales that are recalibrated under standard SF-36 scoring. Results provide justification for scoring translations of individual items using standard SF-36 scoring; whether these items form the same scales in other countries as they do in the United States is evaluated with tests of scaling assumptions.

Analysis of Variance↗
PubMed1998

Translation, adaptation, and validation of the SF-36 Health Survey for use in Japan.

Development of the Japanese SF-36 was completed in two phases: Phase 1: Japanese version 1.1 was produced according to International Quality of Life Assessment (IQOLA) project guidelines, but some results of psychometric tests were unexpected. First, scores varied little across physical-functioning items. Second, using factor analysis, we could not clearly distinguish the scales designed to measure the "physical" component of quality of life from those designed to measure the "mental" component. Phase 2: Focus-group discussions revealed that limited had often been interpreted as limited by a doctor. Therefore, is difficult to do was used instead (version 1.2). Results of two surveys indicated that version 1.2 yields scores that are reliable by internal consistency and test-retest standards and yields two principal components. In Japan, however, the pattern of correlations between some scales and the principal components differs from that in the United States. Iterative use of qualitative and quantitative methods was very important in developing the Japanese SF-36.

Cross-Cultural Comparison↗
PubMed1998

Psychometric and clinical tests of validity of the Japanese SF-36 Health Survey.

Cross-sectional data from a representative sample of the general population in Japan were analyzed to test the validity of Japanese SF-36 Health Survey scales as measures of physical and mental health. Results from psychometric and clinical tests of validity were compared. Principal components analyses were used to test for the hypothesized physical and mental dimensions of health and the pattern of scale correlations with those components. To test the clinical validity of SF-36 scale scores, self-reports of chronic medical conditions and the Zung Self-Rating Depression Scale were used to create mutually exclusive groups differing in the severity of physical and mental conditions. The pattern of correlations between the SF-36 scales and the two empirically derived components generally confirmed hypotheses for most scales. Results of psychometric and clinical tests of validity were in agreement for the Physical Functioning, Role-Physical, Vitality, Social Functioning, and Mental Health scales. Relatively less agreement between psychometric and clinical tests of validity was observed for the Bodily Pain, General Health, and Role-Emotional scales, and the physical and mental health factor content of those scales was not consistent with hypotheses. In clinical tests of validity, the General Health, Bodily Pain, and Physical Functioning scales were the most valid scales in discriminating between groups with and without a severe physical condition. Scales that correlated highest with mental health in the components analysis (Mental Health and Vitality) also were most valid in discriminating between groups with and without depression. The results of this study provide preliminary interpretation guidelines for all SF-36 scales, although caution is recommended in the interpretation of the Role-Emotional, Bodily Pain, and General Health scales pending further studies in Japan.

Adult↗
PubMed1998

Tests of data quality, scaling assumptions, and reliability of the SF-36 in eleven countries: results from the IQOLA Project. International Quality of Life Assessment.

Data from general population samples in 11 countries (n = 1483 to 9151) were used to assess data quality and test the assumptions underlying the construction and scoring of multi-item scales from the SF-36 Health Survey. Across all countries, the rate of item-level missing data generally was low, although slightly higher for items printed in the grid format. In each country, item means generally were clustered as hypothesized within scales. Correlations between items and hypothesized scales were greater than 0.40 with one exception, supporting item internal consistency. Items generally correlated significantly higher with their own scale than with competing scales, supporting item discriminant validity. Scales could be constructed for 93-100% of respondents. Internal consistency reliability of the eight SF-36 scales was above 0.70 for all scales, with two exceptions. Floor effects were low for all except the two role functioning scales; ceiling effects were high for both role functioning scales and also were noteworthy for the Physical Functioning, Bodily Pain, and Social Functioning scales in some countries. These results support the construction and scoring of the SF-36 translations in these 11 countries using the method of summated ratings.

Cross-Cultural Comparison↗
PubMed1998

A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32).

t(9;14)(p13;q32), a subtype of 14q32 translocation, plays an essential role in the development of lymphoplasmacytoid lymphoma. t(9;14)(p13;q32) Causes juxtaposition of the PAX-5 gene on 9p13 and the IgH gene on 14q32, leading to the deregulation of the PAX-5 gene. We report a case of primary splenic lymphoma with a t(9;14). The histological diagnosis was diffuse large B-cell lymphoma without plasmacytoid differentiation. The lymphoma cells showed a complex karyotype including a t(9;14). Southern blot analysis localized the breakpoint of the PAX-5 gene within a couple of kb regions upstream of the exon 1A, although the involvement of the PAX-5 gene with the immunoglobulin heavy chain gene could not be confirmed.

Chromosomes, Human, Pair 14↗
PubMed1998

Advance directives and other medical decisions concerning the end of life in cancer patients in Japan.

The purpose of our survey was to investigate the experience of physicians regarding advance directives and other medical decisions concerning the end of life. A postal questionnaire was sent to 500 Japanese physicians who were most involved in medical care of terminal patients. A total of 339 (68%) physicians responded. In dealing with terminal patients, approximately half gave priority to their patients' wishes for medical care, if known, regardless of the patient's competency. Of the respondents, 149 had been presented with advance directives by their patients and 35% followed all advance directives presented in their practice. Cardiopulmonary resuscitation (CPR) for arrested patients to enable their family to be at the bedside at the time of the death was common. More than 60% of the respondents thought that active euthanasia and assisted suicide were never ethically justified. Our study indicates that the wishes of patients are currently not always given top priority in medical decisions concerning the end of life.

Adult↗
PubMed1998

HLA and HPA typing in idiopathic thrombocytopenic purpura patients treated with Kami-kihi-to.

We performed human leukocyte antigen (HLA) and human platelet antigen (HPA) in patients with Kami-kihi-to-responsive idiopathic thrombocytopenic purpura. The HLA-A2, A61 and Cw1 were significantly increased in responders compared with nonresponders, as were HLA DRB1 *0901, DRB1 *1502, and DPB1 *0501. In contrast, HLA DPB1 *0201 and DPB1 *0901 were significantly decreased in responders. The a/b genotype of HPA-2 and a/a genotype of HPA-3 were markedly increased in nonresponders, and anti-GPIb antibody was also increased. These results suggest that HLA, HPA, and anti-GP antibody studies may predict the response of idiopathic thrombocytopenic purpura to Kami-kihi-to.

Antigens, Human Platelet↗
PubMed1998

[Validation of interviewer administration of the Short Form 36 Health Survey, and comparisons of health-related quality of life between community-dwelling and institutionalized elderly people].

The Short Form 36 Health Survey (SF-36) is a questionnaire that is widely used to measure health-related quality of life. Because self-administered questionnaires may not be appropriate for seriously ill or elderly people, we administered the SF-36 to institutionalized elderly people by face-to-face interviews, and tested its reliability and validity. We also compared the SF 36 score of those subjects with the scores of community-dwelling elderly people. We studied 117 people aged 65 or over who were living in residential facilities on Sado island and 62 randomly sampled elderly people who were living in the community. The SF-36 scores of the institutionalized subjects had acceptable ceiling and floor effects, and their internal consistency, concurrent validity, and construct validity were high. The only exceptions were the scores of the "vitality" subscale. Adjusted mean scores on four subscales were higher among the institutionalized subjects than among those living in the community: role limitation due to physical condition, role limitation due to emotional condition, social functioning, and bodily pain. The two groups did not differ with regard to scores on the "mental health" scale, the "vitality" scale, or the "general health perception" scale. We conclude that the SF-36 can be useful for measuring health-related quality of life among institutionalized elderly people, if it is administered in face-to-face interviews.

Activities of Daily Living↗
PubMed1998

[Anti-fibrinogen antibody detected in a patient with systemic lupus erythematosus and disseminated intravascular coagulation].

A 22-year-old woman was admitted to our hospital with fever, generalized lymphadenopathy, and pancytopenia in February 1995. She was diagnosed as having systemic lupus erythematosus (SLE) based on positivity for anti-nuclear antibody, and polyarthritis among other findings. A diagnosis of disseminated intravascular coagulation (DIC) was made based on the increase of FDP and other data (DIC score: 7). We also detected an anti-fibrinogen antibody. Lymph node biopsy revealed subacute necrotizing inflammation and there were on signs of the hemophagocytic phenomenon in bone marrow. The DIC score improved and the anti-fibrinogen antibody disappeared in association with the response of SLE to prednisolone therapy. The onset of SLE associated with DIC has never been reported before, as far as we could determine. The mechanism of DIC associated with SLE may be related to endothelial damage caused by immune complexes.

Adult↗
PubMed1998

Effect of cilostazol on soluble adhesion molecules and platelet-derived microparticles in patients with diabetes.

We evaluated the plasma concentrations of soluble adhesion molecules and platelet-derived microparticles (PMP) in patients with non-insulin dependent diabetes mellitus (NIDDM) and studied the effect of cilostazol on PMP generation. There were differences in the levels of soluble adhesion molecules between NIDDM patients (N = 43) and the control subjects (N = 30) (soluble thrombomodulin: 11.5+/-5.3 vs. 7.0+/-1.2 TU/ml, p<0.0001; soluble vascular cell adhesion molecule-1: 708+/-203 vs. 492+/-113 ng/dl, p<0.0001; soluble intercellular cell adhesion molecules- 1: 274+/-65 vs. 206+/-48 ng/dl, p<0.0001; soluble P-selectin: 194+/-85 vs. 125+/-43 ng/dl, p<0.0001). There were also differences in the levels of PMP and platelet activation markers between NIDDM patients and the controls (PMP: 943+/-504 vs. 488+/-219/10(4) plt, p<0.0001; platelet CD62P: 9.2+/-4.6 vs. 4.4+/-4.3%, p<0.001; platelet CD63: 10.2+/-4.5 vs. 4.5+/-3.3%, p<0.0001; platelet annexin V: 9.1+/-3.9 vs. 5.3+/-3.8%, p<0.001). To study the release of PMP into plasma, a modified cone-and-plate viscometer was used. Increased release of PMP from platelets was observed in diabetic plasma compared to normal plasma under high shear stress conditions (2,672+/-645 vs. 1,498+/-386/10(4) plt, p<0.05). Therefore, one cause of PMP elevation in NIDDM may be high shear stress. The levels of PMP, activated platelets, and soluble adhesion molecules all decreased significantly after treatment with cilostazol. These results suggest that cilostazol may be useful for the inhibition of both PMP-dependent and -independent vascular damage in NIDDM.

Adult↗
PubMed1998

Clinical evaluation of transfusion of prestorage-leukoreduced apheresis platelets.

UNLABELLED: With increased use of platelet concentrate (PC) in recent years, adverse reactions to PC transfusion have received much clinical attention. Most of these reactions stem from white blood cells (WBC) contaminating the transfused PC. Several are thought to be preventable by removing WBC before PC storage. METHODS: We routinely filtered apheresis PC either during collection or immediately afterwards and monitored various indicators of platelet quality during storage. After transfusion to patients, transfusion efficacy and the type, severity, and frequency of posttransfusion side effects were compared with those of a control group in which PC was filtered at the bedside. RESULTS: Prestorage-filtered PC contained an average of 3.1+/-0.7 x 10(11) platelets and 0.9+/-1.2 x 10(6) contaminating leukocytes. Measurement of platelet function and metabolic indicators revealed normal values throughout the storage period. CD62 measurement revealed no undue platelet activation after filtration or during the storage period. Cytokine, histamine, bradykinin, and complement levels showed no significant increase after filtration or during storage. Transfusion efficacy and overall side effect incidence rates were similar for the prestorage- and bedside-filtered groups, but reactions of the bedside-filtered group included serious reactions such as breathing difficulties and shock. No serious reactions were noted in the prestorage-filtered group. CONCLUSION: Filtering PC before storage has no adverse effect on PC quality and may reduce the severity of post transfusion side effects.

Blood Platelets↗