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Biomedical subjects

S Kosugi

Publications and source records attributed to S Kosugi.

At least 19 recordsLinked to original sources
PubMed2006

How do bioethics teachers in Japan cope with ethical disagreement among healthcare university students in the classroom? A survey on educators in charge.

OBJECTIVE: The purpose of this study was to demonstrate how educators involved in the teaching of bioethics to healthcare university students in Japan would cope with ethical disagreement in the classroom, and to identify factors influencing them. METHODS: A cross sectional survey was conducted using self administered questionnaires mailed to a sample of university faculty in charge of bioethics curriculum for university healthcare students. RESULTS: A total of 107 usable questionnaires were returned: a response rate of 61.5%. When facing ethical disagreement in the classroom, coping behaviour differed depending on the topic of discussion, was influenced by educators' individual clear ethical attitudes regarding the topic of discussion, and was independent of many respondents' individual and social backgrounds. Among educators, it was commonly recognised that the purpose of bioethics education was to raise the level of awareness of ethical problems, to provide information about and knowledge of those issues, to raise students' sensitivity to ethical problems, and to teach students methods of reasoning and logical argument. Yet, despite this, several respondents considered the purpose of bioethics education to be to influence students about normative ethical judgments. There was no clear relationship, however, between ways of coping with ethical disagreement and educators' sense of the purpose of bioethics education. CONCLUSIONS: This descriptive study suggests that educators involved in bioethics education for healthcare university students in Japan coped in various ways with ethical disagreement. Further research concerning ethical disagreement in educational settings is needed to provide better bioethics education for healthcare students.

Adaptation, Psychological↗
PubMed2006

Pretreatment with magnesium sulphate is associated with less succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemodynamic changes than precurarization with vecuronium during rapid sequence induction.

Although it has side effects, succinylcholine is still widely used in rapid sequence induction. The aim of the present study is to evaluate the effects of pretreat ment with magnesium and precurarization of vecuroni um on succinylcholine-induced fasciculation and subse quent tracheal intubation-induced hemodynamic changes during rapid sequence induction. Fifty-five patients were allocated to three groups by a blinded randomization: Group M received saline 100 ml with magnesium 40 mg x kg(-1) for 5 min at 6.5 min before induction and sub sequently administered saline 1-2 ml at 1.5 min before induction; Group V received saline 100 ml for 5 min at 6.5 min before induction and subsequently administered vecuronium 0.02 mg x kg(-1) at 1.5 min before induction; Group C received saline 100 ml for 5 min at 6.5 min before induction and then saline 1-2 ml at 1.5 min before induction. Fasciculation scores and mean percent changes of heart rate, systolic blood pressure and rate pressure product between baseline and after induction were significantly lower in group M than those in group C and group V. Pretreatment with magnesium is more effective to limit succinylcholine-induced fasciculation and subsequent tracheal intubation-induced hemody namic changes in rapid sequence induction compared with vecuronium pretreatment, although magnesium does not prevent the elevation of serum potassium con centration after induction.

Adult↗
PubMed2005

Polymorphisms in PTCH1 affect the risk of ameloblastoma.

Ameloblastoma is the most common odontogenic tumor, but the genetic nature of the changes in the tumor cells has been unclear. Mutations of CTNNB1 or PTCH1 are observed in many human tumors. Both CTNNB1 and PTCH1 are important in tooth development and are expressed in ameloblastoma. The aim of this study was to investigate whether genetic alterations of CTNNB1 and PTCH1 are present in ameloblastoma. We investigated 14 cases of ameloblastoma. The polymorphisms found in the ameloblastoma patients were further examined in a subsequent case-control study. We found a CTNNB1 mutation in one case of plexiform-type ameloblastoma. CGG triplet repeat-number polymorphism (CGG7/CGG8) in the 5'-untranslated region of PTCH1 was observed. The proportion of CGG8 alleles was significantly higher in the ameloblastoma group. The results of this study indicate a possible relationship between the CGG8 allele in PTCH1 and the risk for ameloblastoma.

Adult↗
PubMed2004

Self-expandable metallic stents for palliation of malignant esophageal obstruction: special reference to quality of life and survival of patients.

SUMMARY. Self-expandable metallic stents (EMS) provide a common option for malignant esophageal stenosis because of the low complication rate and high dysphagia improvement rate. However, there are few studies on the functional duration of EMS and the extent of improvement of the quality of life. We retrospectively analyzed 18 patients who received EMSs in our division from 1996 to 2002. The median duration of possible food intake and the median survival period were 94.5 and 108 days. The median duration of domiciliary treatment was 56 days. Six of the 18 patients were not discharged from hospital after EMS insertion. The Karnofsky index was found to be a significant determinant of the feasibility of domiciliary treatment. One-third of the patients are incapable of obtaining the benefits of the palliative therapy. EMS deployment should be prudently selected for patients exhibiting low performance status.

Adult↗
PubMed2004

Activation of integrin alpha IIb beta 3 in the glycoprotein Ib-high population of a megakaryocytic cell line, CMK, by inside-out signaling.

Affinity/avidity state of integrin alpha IIb beta 3 is regulated by intracellular inside-out signaling. Although several megakaryocytic cell lines have been established, soluble ligand binding to alpha IIb beta 3 expressed in these cells by cellular agonists has not been demonstrated. We have re-examined agonist-induced alpha IIb beta 3 activation on megakaryocytic cell lines with a marker of the late stage of megakaryocytic differentiation, glycoprotein Ib (GPIb). Activation of alpha IIb beta 3 was assessed by PAC1 and soluble fibrinogen binding to the cells. We found that alpha IIb beta 3 expressed in CMK cells with high GPIb expression was activated by a phorbor ester, phorbol myristate acetate (PMA). Although the population of the GPIbhigh cells was <0.5% of the total cells, incubation with a nucleoside analog, ribavirin, efficiently increased the PMA-reactive GPIbhigh cells. Not only PMA but also a calcium ionophore, A23187, induced alpha IIb beta 3 activation, and PMA and A23187 had an additive effect on alpha IIb beta 3 activation. Ligand binding to the activated alpha IIb beta 3 in the GPIbhigh CMK cells is totally abolished by an alpha IIb beta 3-specific antagonist, and inhibited by wortmannin, cytochalasin-D and prostaglandin E1, and the effects of these inhibitors on alpha IIb beta 3 activation in the GPIbhigh CMK cells were compatible with those in platelets. We have also demonstrated that the ribavirin-treated CMK cells express PKC-alpha, -beta, -delta and -theta, and suggested that PKC-alpha and/or -beta appear to be responsible for PMA-induced activation of alpha IIb beta 3 in CMK cells.

Alprostadil↗
PubMed2003

Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus.

The role of cervical lymphadenectomy for thoracic esophageal cancer is controversial. This study evaluated the impact of cervical lymphadenectomy on the cervical lymph node metastasis (LNM) and survival rates of patients with esophageal cancer. We analyzed 199 patients who received radical esophagectomy with three-field lymphadenectomy. The overall 5-year survival rate was 49.4%. Cervical LNM was found in 36 (18.1%) out of the 199 patients. The 5-year survival rates of the patients with cervical LNM from upper and mid-esophageal cancers were 71.4% and 35.9%, respectively. However, none of the patients with cervical LNM from lower esophageal cancer survived more than 4 years after esophagectomy. The overall survival of patients with five or more metastatic nodes (5.9%) was significantly worse than that of patients with less than five positive nodes (45.5%). Cervical lymphadenectomy is beneficial for patients with carcinoma of the upper and mid-thoracic esophagus, and with less than five positive nodes.

Adult↗
PubMed2002

Sevoflurane preconditions stunned myocardium in septic but not healthy isolated rat hearts.

BACKGROUND: Recent evidence indicates that sevoflurane treatment before prolonged ischaemia reduces infarct size in normal hearts, mimicking ischaemic preconditioning. We examined whether exposure to sevoflurane before brief ischaemia, inducing a 'stunned myocardium', provided such protective effects in an isolated working heart from normal or septic rats. METHODS: With institutional approval, 91 rats were randomly allocated into one of either caecal-ligation and perforation (CLP: n=50) or sham (Sham: n=41) procedure groups 24 h before the study. After determination of baseline measurements, including cardiac output (CO), myocardial oxygen consumption (mVO(2)) and cardiac efficiency (CE; CO x peak systolic pressure/mVO(2)), each isolated heart was perfused with or without 2% sevoflurane for 15 min before global ischaemia (pre-ischaemia). After 15 min ischaemia and 30 min reperfusion, all hearts were assessed for functional recovery of myocardium (post-reperfusion). RESULTS: During the pre-ischaemia period, 2% sevoflurane caused a significant reduction of CO in the CLP group compared with the Sham group. During the post-reperfusion period, both CO (16.9 vs 11.0 ml min(-1)) and CE (11.2 vs 7.7 mm Hg ml(-1) ( micro l O(2))(-1)) was higher in the sevoflurane-treated vs -untreated hearts from CLP rats, and was accompanied by lower incidence of reperfusion arrhythmia compared with control hearts (8 vs 32%). In contrast, 2% sevoflurane did not provide cardioprotective effects in normal rats. CONCLUSIONS: The current study demonstrates that pre-treatment with sevoflurane minimizes myocardial dysfunction and the incidence of reperfusion arrhythmia after brief ischaemic insults in septic hearts.

Anesthetics, Inhalation↗
PubMed2001

Platelet-associated anti-GPIIb-IIIa autoantibodies in chronic immune thrombocytopenic purpura recognizing epitopes close to the ligand-binding site of glycoprotein (GP) IIb.

Localization of epitopes for platelet-associated (PA) anti-GPIIb-IIIa (alpha(IIb)beta(3)) autoantibodies in chronic immune thrombocytopenic purpura remains elusive. Previous studies suggest that PA antibodies recognize the tertiary structure of intact glycoprotein (GP) IIb-IIIa. To localize their epitopes using antigen-capture enzyme-linked immunosorbent assay (ELISA), the reactivity of 34 PA anti-GPIIb-IIIa antibodies was examined with recombinant GPIIb-IIIa having a defect in ligand-binding sites in either GPIIb or GPIIIa, and no major conformational change was induced: KO variant GPIIb-IIIa was attributed to a 2-amino acid insertion between residues 160 and 161 in the W3 4-1 loop in GPIIb, and CAM variant GPIIb-IIIa was attributed to D119Y in GPIIIa. In one third (11 of 34) of the patients, PA antibodies showed a marked decrease (less than 50%) in reactivity with KO compared with wild-type GPIIb-IIIa. Their reactivity was also impaired against GPIIbD163A-IIIa. In sharp contrast, they reacted normally with CAM GPIIb-IIIa. OP-G2, a ligand-mimetic monoclonal antibody, markedly inhibited their binding to GPIIb-IIIa in patients with impaired binding to KO GPIIb-IIIa, but small GPIIb-IIIa antagonists did not. In addition, a newly developed sensitive ELISA indicated that autoantibodies showing impaired binding to KO are more potent inhibitors for fibrinogen binding. The present data suggest that certain PA anti-GPIIb-IIIa autoantibodies recognize epitopes close to the ligand-binding site in GPIIb, but not in GPIIIa.

Adult↗
PubMed2001

Ligand binding to integrin alpha(v)beta(3) requires tyrosine 178 in the alpha(v) subunit.

Integrin alpha(v)beta(3) has been implicated in angiogenesis and other biological processes. However, the ligand-binding sites in alpha(v), a non-I-domain alpha subunit, remain to be identified. Recently in alpha(IIb), the other partner of the beta(3) subunit, several discontinuous residues important for ligand binding were identified in the predicted loops between repeats 2 and 3 (W3 4-1 loop) and within repeat 3 (W3 2-3 loop). Based on these findings, alanine-scanning mutagenesis in 293 cells was used to investigate the role of these loops (cysteine [C]142-C155 and glycine [G]172-G181) of alpha(v) in ligand binding. Wild-type alpha(v)beta(3) was able to bind soluble fibrinogen following integrin activation either by 0.5 mM manganese dichloride (MnCl(2)) or a mutation of beta(3) threonine (T)562 to asparagine. However, mutation of tyrosine (Y)178 to alanine in the predicted G172-G181 loop of alpha(v) abolished fibrinogen binding, and alanine (A) substitutions at adjacent residues phenylalanine (F)177 and tryptophan (W)179 had a similar effect. Cells expressing Y178Aalpha(v) also failed to bind to immobilized fibrinogen. Moreover, the Y178A mutation abolished the binding of WOW-1 Fab, a monovalent ligand-mimetic anti-alpha(v)beta(3) antibody, and the expression of beta(3) ligand-induced binding sites (LIBS) induced by arginine-glycine-aspartic acid-tryptophan (RGDW). In sharp contrast to the data obtained with alpha(IIb), none of the mutations in the predicted W3 4-1 loop in alpha(v) impaired ligand binding. These results implicate alpha(v) Y178 in ligand binding to alpha(v)beta(3), and they suggest that there are key structural differences in the adhesive ligand-binding sites of alpha(v)beta(3) and alpha(IIb)beta(3).

Amino Acid Sequence↗
PubMed2001

Analyses of genetic abnormalities in type I CD36 deficiency in Japan: identification and cell biological characterization of two novel mutations that cause CD36 deficiency in man.

To elucidate genetic abnormalities in type I CD36 deficiency, we analyzed 28 Japanese subjects whose platelets and monocytes/macrophages lacked CD36 on their surface. We identified two novel mutations in the CD36 gene. One was a complex deletion/insertion mutation, in which 3 bp, GAG, were deleted at nucleotide (nt) 839-841, and 5 bp, AAAAC, were inserted at the same position (839-841del-->insAAAAC). Mutation 839-841del-->insAAAAC led to a frameshift and appearance of a premature stop codon; it was also accompanied with a marked reduction in the amount of CD36 mRNA. The other was a 12-bp deletion at nt 1438-1449 (1438-1449del) accompanied with or without skipping of exon 9 (nt 959-1028). Mutation 1438-1449del led to an inframe 4-amino-acid deletion, whereas exon 9 skipping led to a frameshift and the appearance of a premature stop codon. Expression assay revealed that both 1438-1449del and exon 9 skipping directly caused impairment of the surface expression of CD36. A survey of the five known mutations including 839-841del-->insAAAAC and 1438-1449del in type I CD36-deficient subjects demonstrated that the five mutations covered more than 90% of genetic defects among them and that the substitution of T for C at nt 478 (478C-->T) was the most common mutation with more than 50% frequency. However, none of the four subjects that possessed isoantibodies against CD36 had 478C-->T, suggesting that 478C-->T prevents the production of isoantibodies against CD36.

Alleles↗
PubMed2001

Successful non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) for Waldenström's macroglobulinemia with severe pancytopenia.

We report a 62-year-old male who underwent non-myeloablative allogeneic peripheral blood stem cell transplantation (PBSCT) because of his life-threatening severe pancytopenia due to refractory Waldenström's macroglobulinemia. This therapy was performed safely and he made a marked recovery from his cytopenia that had not been improved with any other therapy. Bone marrow aspirates showed post-transplant mixed chimerism during engraftment, and became completely donor-derived after a series of GVHD symptoms, without subsequent donor lymphocyte infusion. Our results suggest that non-myeloablative allogeneic PBSCT could be a good alternative for patients suffering from multi-drug resistant Waldenström's macroglobulinemia.

Critical Illness↗
PubMed2001

A novel germline mutation of the MEN1 gene, L259del, in a patient with sporadic multiple endocrine neoplasia type 1 (MEN1).

A Japanese woman was treated for insulinoma when she was 29 years old. Ten years later, heperparathyroidism and non-functioning adrenal tumor were found and she was diagnosed as having multiple endocrine neoplasia type 1 (MEN1). No other family members have developed MEN-related lesion(s). Genomic DNA of the patient was analyzed by sequencing for the MEN1 gene and a novel, three-base in-frame deletion resulting in deletion of an amino acid Leu259 was identified. Her two children showed a wild-type sequence at this codon.

Adult↗
PubMed2001

Diagnostic value of tests for reticulated platelets, plasma glycocalicin, and thrombopoietin levels for discriminating between hyperdestructive and hypoplastic thrombocytopenia.

We measured reticulated platelets (RPs) and plasma glycocalicin (GC) and thrombopoietin (TPO) levels simultaneously in 107 thrombocytopenic patients to clarify the diagnostic value of these tests for discriminating hyperdestructive from hypoplastic thrombocytopenia. The percentage of RPs and GC index (plasma GC level normalized for the individual platelet count) were markedly elevated in patients with idiopathic thrombocytopenic purpura (ITP) but normal or slightly elevated in patients with aplastic anemia (AA) or chemotherapy-induced thrombocytopenia (ChemoT). For RP percentage for diagnosing hyperdestructive thrombocytopenia the sensitivity and specificity were excellent but were lower for the GC index. Absolute RP counts and plasma GC levels were markedly decreased and plasma TPO levels markedly elevated in patients with AA or ChemoT, but absolute RP counts and plasma GC levels were moderately decreased and plasma TPO levels only slightly elevated in patients with ITP. The sensitivity and specificity of plasma TPO levels for diagnosing hypoplastic thrombocytopenia were excellent. Using the RP percentage and plasma TPO levels in combination improved specificities. Simultaneous measurement of RP percentage and plasma TPO level may help discriminate thrombocytopenia of unknown cause in routine hematologic practice.

Adult↗
PubMed2001

[Psychological counseling as a management of stress in work place].

We have made psychological counseling service a part of a mental health program for 10,700 employees since 1980. Our counseling method is based on a psychological stress model and divided into three steps. The first is psychological stress survey by means of the Job Stress Scale (JSS). JSS was administered to a group of about 500 employees. The result of the JSS is reported to each employee by in-house letter. The second is a substructured interview for maladjusted employees found in JSS psychological stress reactions scores. The interviewer explains each of the JSS sub-scales such as job stressors, coping strategies, social support, and psychological stress reactions to interviewees. The last is psychological counseling. Counselees are chosen by the interviewer according to the following conditions: 1) request for counseling, 2) need for psychiatric treatment, 3) strong psychological stress reactions in spite of low job stressors, 4) signs of family problems. These four steps may decrease an employee's resistance to counseling.

Counseling↗
PubMed2001

Anti-alphavbeta3 antibodies in chronic immune thrombocytopenic purpura.

In chronic immune thrombocytopenic purpura (ITP), anti-GPIIb-IIIa (alphaIIbbeta3) autoantibodies have been detected in serum and/or platelet-associated IgG (PAIgG) and considered as one of the major causes. We examined whether anti-alphavbeta3 antibodies might be present in ITP cases because of the similarity between alphavbeta3 and GPIIb-IIIa (alphaIIbbeta3). Modified antigen capture ELISA (MACE) using human umbilical vein endothelial cells (HUVEC) showed the presence of serum anti-alphavbeta3 antibodies in 23 of 80 ITP patients (29%). Cross-adsorption studies between platelets and HUVEC demonstrated that most of anti-alphavbeta3 and anti-GPIIb-IIIa antibodies exclusively reacted with alphavbeta3 and GPIIb-IIIa, respectively. Platelet-associated anti-GPIIb-IIIa antibodies did not react with alphavbeta3, either. Interestingly, patients having anti-alphavbeta3 antibodies showed significantly lower platelet counts than negative patients. These results indicate the serum anti-alphavbeta3 antibodies are different ones from the classical anti-GPIIb-IIIa (alphaIIbbeta3) antibodies and would provide a new insight into the pathophysiology of ITP as well as the autoantigenic epitopes on beta3 integrins.

Autoantibodies↗
PubMed2000

Cloning and DNA-binding properties of a tobacco Ethylene-Insensitive3 (EIN3) homolog.

Ethylene-Insensitive3 (EIN3) is a transcription factor that works in the ethylene signaling pathway in Arabidopsis. We isolated a tobacco cDNA encoding an EIN3 homolog as a sequence-specific DNA-binding protein. The encoded protein TEIL (tobaccoEIN3-like) shares 60% identity in amino acid sequence with EIN3. The DNA-binding domain was localized in the N-terminal half, which shows 92% identity in amino acid sequence with the corresponding region of EIN3, suggesting a conserved function in DNA-binding specificity. TEIL was indeed functionally similar to EIN3 because, like EIN3-overexpressing plants, transgenic Arabidopsis seedlings overexpressing TEIL cDNA exhibited constitutive triple response phenotypes. Random binding site selection analysis revealed that the consensus binding sequence for TEIL is AYGWAYCT, where Y and W represent A or C and A or T, respectively. A reporter plasmid containing the TEIL binding sites showed a 7- to 10-fold higher activation relative to that containing a mutated TEIL-binding sequence in tobacco protoplasts. A further 2- to 3-fold increase in activation was observed when a plasmid for TEIL overproduction was co-transfected, indicating that TEIL is a transcriptional activator. Moreover, nuclear extracts from ethylene-treated leaves showed an increase in DNA-binding activity specific to the TEIL-binding sequence, despite the level of the transcripts being unchanged. These observations suggest that TEIL functions as a transcription activator with a relatively redundant DNA-binding specificity, and its function may be regulated at least in part by modulation of the DNA-binding activity through ethylene signaling.

Amino Acid Sequence↗
PubMed2000

Gene diagnosis and clinical management of multiple endocrine neoplasia type 1 (MEN1).

Identification of the MEN1 gene as a disease gene for multiple endocrine neoplasia type 1 (MEN1) has made it possible to predict whether a family member of an MEN1 patient will suffer from the same disease. MEN1 mutations have been found in almost all cases with familial MEN 1, but in fewer cases with sporadic MEN1. We analyzed MEN1 mutations in the largest number of Japanese MEN1 patients, 17 families and 21 sporadic cases, and found 54 MEN1 mutant carriers and 30 non-carriers. Furthermore, we identified a MEN1 phenocopy: GH-secreting pituitary tumor and primary hyperparathyroidism, which develops at older ages. In this article, we discuss how to utilize MEN1 gene diagnostics for the clinical management of MEN 1 patients and MEN1 mutation carriers.

Humans↗