PubMed Health⌕ Search

Biomedical subjects

Y Iwatani

Publications and source records attributed to Y Iwatani.

At least 19 recordsLinked to original sources

[Extensive educational program for high performance medical technologists].

The education system for medical technologists has recently been revolutionized, their educational periods vary from 2 to 9 years, and some already have doctoral degrees. In such a new situation, our faculty thinks that the most important point for new medical technologists is the ability to have a broad view of the clinical fields, especially the view of patients. Special training in bed-side education and a stint in several divisions, such as the surgical operation room, rehabilitation. radiological examination room, pharmacy, central storage room of medical records, and medical informatics, and so on, of the hospital is a powerful tool to obtain a broad view of the various clinical fields and can be essential for developing high performance medical technologists. As nine years have passed since starting this education, we evaluated this practice through systematic personal communication. As a result, it was found to be extremely effective for many reasons such as having a continuous image of the patient when they examine the blood sample in the hospital laboratory, showing advanced laboratory performance, and having no mental barrier to visiting the wards and so on. The abilities of our alumni are praised highly by many large scale hospitals around the country and 50% of them are working in the clinical laboratory division of these hospitals. About 40% are working in the division of research and development in various companies. We express sincere thanks to the director and all cooperative individuals for this course in the Osaka University Hospital.

Curriculum↗

Decrease of CD154 intensity on peripheral CD4+ T cells in autoimmune thyroid disease.

To clarify immunological differences among patients with Graves' disease (GD) and Hashimoto's disease (HD) at various levels of severity, we examined the expression of the CD154 molecules on peripheral T cells, which regulate B cell activation, B cell differentiation, and T-cell survival. We found decreases in the intensities of CD154 on peripheral CD4(+) cells from euthyroid patients with GD and HD, but we did not find any differences between patients with different disease severities. CD8(+) cells did not express CD154 molecules. Thus, CD154 expression on CD4(+) cells may be related to the pathogenesis of the autoimmune thyroid diseases, not to the disease severity.

Adult↗

Lower concentration of serum soluble CD8 in severe Hashimoto's disease.

To investigate the roles of soluble CD4 (sCD4) and CD8 (sCD8) in the severity of autoimmune thyroid diseases, we examined serum concentrations of sCD4 and sCD8 in various degrees of severity of Hashimoto's disease (HD) and Graves' disease (GD) by enzyme immunoassay. The serum concentration of sCD8 was lower in euthyroid patients with HD undergoing treatment for hypothyroidism (severe HD) than in untreated, euthyroid patients with HD (mild HD), but the sCD4 concentration did not differ between patients with severe and mild HD. The serum sCD8 concentration was negatively correlated with the proportion of CD25(+) cells in CD8(+) cells in patients with severe HD. Serum sCD4 and sCD8 concentrations did not differ between euthyroid patients with GD in remission and those with intractable GD. These results indicate that serum sCD8 is involved in the severity of HD, possibly by down-regulating the function of cytotoxic T cells.

CD4 Antigens↗

High frequency of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive Clostridium difficile in a hospital in Japan and risk factors for infection.

Patients hospitalized in a hospital with a high incidence of antibiotic-associated diarrhea due to toxin A-negative, toxin B-positive (A-/B+) Clostridium difficile were retrospectively investigated to determine the clinical manifestations and risk factors for infection. Of 77 Clostridium difficile isolates obtained from 77 patients during the 1-year investigation period, 30 were A-/B+ and 47 were toxin A-positive, toxin B-positive (A+/B+). By pulsed-field gel electrophoresis analysis, 23 of the 30 A-/B+ strains were outbreak-related, suggesting nosocomial spread of a single type of bacterium, which mainly affected patients in the wards of respiratory medicine, hematology and neurology. Using regression analysis, three factors were found to be associated with infection by A-/B+ isolates: (i) exposure to antineoplastic agents ( P=0.01, odds ratio [OR]=5.1), (ii) the use of nasal feeding tubes ( P=0.008, OR=5.2), and (iii) assignment to a certain internal medicine ward ( P=0.05, OR=3.0). Between patients with Clostridium difficile-associated diarrhea caused by A-/B+ strains and those with A+/B+ strains, no statistically significant difference was found in body temperature, serum concentration of C-reactive protein, leukocyte count in whole blood, frequency of diarrhea, or type of underlying disease. These results indicate that A-/B+ strains of Clostridium difficile can cause intestinal infection in humans and they spread nosocomially in the same manner as A+/B+ strains.

Adolescent↗

In vitro combined effects of cefozopran/teicoplanin and cefozopran/vancomycin on methicillin-resistant Staphylococcus aureus.

We determined the in vitro effects of teicoplanin (TEIC) or vancomycin (VCM) added to cefozopran (CZOP) on 50 methicillin-resistant Staphylococcus aureus (MRSA) strains, using a modified checkerboard method with serial 1.25-fold dilutions, and assessed the time-kill curve. CZOP + TEIC was synergistic (fractional inhibitory concentration index < or = 0.5) against 98% and CZOP + VCM against 20% of strains. Both drug combinations were additive against the remaining strains. A comparison of the fractional bactericidal concentration indices for 32 strains showed synergistic bactericidal effects for CZOP + TEIC in 88%, and in 48% for CZOP +VCM, confirming that CZOP + TEIC is superior to CZOP + VCM. The time-kill curve confirms that the bactericidal potency of these drugs is increased through combined use with CZOP. These results suggest that treatment using TEIC or VCM with CZOP may be useful in treating MRSA infections, including polymicrobial infections and those involving Gram-negative rods.

Anti-Bacterial Agents↗

Analysis of dominant-negative effects of mutant Env proteins of human immunodeficiency virus type 1.

The Env protein of human immunodeficiency virus type 1 is assembled into a stable trimer, and oligomerization is required for maintenance of viral infectivity. This property of Env suggests that Env mutants may have a dominant-negative effect on virus infectivity. To investigate this possibility, we established a packaging cell line in which both wild-type and mutant Env proteins could be expressed simultaneously in a single cell. We analyzed the effects of two types of Env mutants: cytoplasmic tail-truncated TM mutants and a mutant defective in gp120/gp41 cleavage. The cytoplasmic tail-truncated proteins were found to be incorporated into virions by forming an oligomer with wild-type TM, but could not inhibit the wild-type function. In contrast, phenotypic mixing of cleavage-defective Env with the wild-type protein caused dramatic inhibition of infectivity, indicating that this mutant has a strong dominant-negative phenotype.

Acquired Immunodeficiency Syndrome↗

Increase of CD5(+) B cells during adolescence in female mice.

We examined physiological changes in CD5(+) B lymphocytes in mice associated with aging (from 1 or 5 to 50 weeks of age). The most predominant populations of lymphocytes among these mice were mainly CD5(-) B cells in the spleen and peritoneal cavity, and T cells in the thymus. However, in the spleen, CD5(+) B cells increased from 1 to 15 weeks, and then decreased with aging. In the thymus, CD5(+) B cells increased from 3 to 9 weeks of age, and subsequently became more predominant than CD5(-) B cells. In the peritoneal cavity, CD5(+) B cells increased from 5 to 9 weeks of age, became the most predominant population in lymphocytes at 7 to 9 weeks of age, and decreased with aging. The proportion of CD5(+) B cells in total B cells increased from 5 to 7 or 9 weeks of age, and then decreased with aging, with the highest proportion at 9 weeks of age in the spleen (15%), thymus (94%), and peritoneal cavity (54%). These findings indicate that CD5(+) B cells increase physiologically during mouse adolescence, and subsequently decrease with aging.

Aging↗

Modification of virus infectivity by cytoplasmic tail of HIV-1 TM protein.

Envelope glycoprotein incorporation is an essential process in formation of infectious particles of human immunodeficiency virus. Accumulated data have indicated that the cytoplasmic tail of Env gp41 is required for efficient incorporation. By analyzing mutant viruses with truncated cytoplasmic tails, we found that the domain was required in a cell-type-dependent manner for maintaining virus infectivity. Although the viruses with truncated cytoplasmic tails produced from HeLa, A3.01 and SupT1 cells showed a greatly reduced infectivity, those from SW480 and MT-4 cells retained a significant infectivity. To clarify the different effect of the cytoplasmic tail mutation on virus infectivity, we performed biochemical studies on the virions produced from HeLa and SW480 cells. Although the truncation of cytoplasmic tail appeared to reduce the Env incorporation in both cell lines, it caused a significant incorporation of Env precursor with HeLa cells. The results suggested that the cytoplasmic tail regulated selective incorporation of processed Env into virions in a cell-type-dependent manner.

Cell Line↗

Anti-prothrombin antibodies combined with lupus anti-coagulant activity is an essential risk factor for venous thromboembolism in patients with systemic lupus erythematosus.

Anti-prothrombin antibodies (anti-prothrombin) and anti-beta2-glycoprotein I antibodies (anti-beta2-GP I) are the most common and characterized anti-phospholipid antibodies (aPL) detected using specific enzyme-linked immunosorbent assay (ELISA) systems. Recently, lupus anti-coagulant (LA) activity detected by a phospholipid-dependent coagulation assay was reported to be associated with anti-prothrombin and/or anti-beta2-GP I. Here we show that the co-existence of IgG anti-prothrombin and LA activity might be an essential risk factor for venous thromboembolism (VTE) in patients with systemic lupus erythematosus (SLE). We examined not only the levels of antibodies to prothrombin and anti-beta2-GP I (both IgG and IgM isotypes) using an ELISA system, but also LA activity detected using both diluted Russell's viper venom time (dRVVT) and STACLOT LA test in 124 patients with SLE. The SLE patients were divided into four groups according to the results of ELISA and LA assay results for each aPL: group A, ELISA+ and LA+ group B, ELISA+ and LA-; group C, ELISA- and LA+ group D, ELISA- and LA-. Regarding IgG anti-prothrombin, the prevalence of VTE was significantly higher in group A (16/35 cases, 45.7%, P < 0.001, Fisher's exact probability test) than in the other groups (B, 2/30, 6.7%; C, 1/22, 4.5%; D, 1/37, 2.7%). With respect to IgM anti-prothrombin and IgG or IgM anti-beta2-GP I, the prevalence of VTE was higher in both groups A and C than in group D, but no statistical difference in prevalence was found between groups A and C. Multivariate logistic regression analysis of risk factors for VTE confirmed that the co-existence of IgG anti-prothrombin and LA activity was the only significant risk factor for VTE (odds ratio, 19.13; 95% confidence intervals, 4.74-77.18).

Adolescent↗

A thiol proteinase inhibitor, E-64-d, corrects the abnormalities in concanavalin A cap formation and the lysosomal enzyme activity in leucocytes from patients with Chediak-Higashi syndrome by reversing the down-regulated protein kinase C activity.

We have reported previously that the abnormally down-regulated protein kinase C (PKC) causes cellular dysfunction observed in natural killer (NK) cells, polymorphonuclear leucocytes (PMNs) and fibroblasts from beige mouse, an animal model of Chediak-Higashi syndrome (CHS). Here we show that the abnormal down-regulation of PKC activity also occurs in Epstein-Barr (EB) virus-transformed cell lines from CHS patients. When CHS cell lines were stimulated with concanavalin A (Con A) for 20 min, the membrane-bound PKC activity declined markedly, whereas that in control cell lines increased. We found that E-64-d, which protects PKC from calpain-mediated proteolysis, reversed the declined PKC activity and corrected the increased Con A cap formation to almost normal levels in CHS cell lines. We confirmed that the dysregulation of PKC activity also occurred in peripheral blood mononuclear leucocytes (PBMC) from CHS patients and that E-64-d corrected both the declined PKC activity and increased Con A cap formation. E-64-d also corrected the reduced lysosomal elastase and cathepsin G activity in CHS cell lines. In contrast, chelerythrin, a specific inhibitor of PKC, and C2-ceramide, which promotes PKC breakdown induced by calpain, increased Con A cap formation and inhibited both elastase and cathepsin G activity in normal cell lines. Moreover, we found that ceramide production in CHS cell lines increased significantly after Con A stimulation, which coincides with our previous observation in fibroblasts from CHS mice. These results suggest an association between ceramide-induced PKC down-regulation and the cellular dysfunctions in CHS.

Calpain↗

Glycyrrhizin enhances interleukin-12 production in peritoneal macrophages.

Interleukin-12 (IL-12) is a monocyte/macrophage-derived cytokine that plays a prominent role in the development of T helper type 1 (Th1) cell-mediated immune responses. Glycyrrhizin (GL), an aqueous extract of liquorice root, used as Chinese medicine, is known to have various immunomodulating activities. In this study, GL showed a dose-dependent priming effect on lipopolysaccharide (LPS)-induced IL-12 p40 and IL-12 p70 (heterodimer of p40 and p35) protein production by peritoneal macrophages (PM). The maximal effect was observed when GL was intraperitoneally administered 12 hr before the PM were harvested and stimulated in vitro with LPS. The increases in IL-12 p70 and p40 protein production were primarily due to up-regulated transcription of IL-12 p35 and p40 messenger RNAs (mRNAs), as demonstrated by RNase protection assay. The augmentation of IL-12 p40 mRNA expression induced by GL pretreatment was associated with increased NF-kappaB activation. Moreover, GL exhibited the same priming effect on IL-12 production in interferon-gamma knockout (IFN-gamma-/-) mice. The production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was not induced at any time point after GL pretreatment. These findings demonstrated the ability of GL to enhance LPS-induced IL-12 production by peritoneal macrophages, and indicated that the priming effect of GL on IL-12 production was independent of both IFN-gamma and GM-CSF.

Animals↗

[Informed consent for the use of the remaining portion of laboratory specimens for education, research, and quality control of laboratory tests].

The remaining portion of a laboratory specimen is usually used for education, research, and quality control of laboratory tests in hospitals, but informed consent has not been obtained because of the high volume of patients who undergo laboratory tests. However, patients must be informed in some manner. Therefore, we decided to inform patients that any remaining specimen would be used for various purposes by placing such a notice on walls in the central clinical laboratory and hospital lobby. We then obtained a signature on a dissent document, instead of a consent document, from any patient who dissented from such use. This indirect process for obtaining informed consent was approved by the ethics committee of Osaka University Medical School. The number of dissent documents sent in to the director was 54 of about 400,000 patients who underwent laboratory tests over the last 3 years, and there was no complaint against this "informed consent process".

Clinical Laboratory Techniques↗

Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications.

BACKGROUND: Anti-phospholipid (aPL) antibodies (Abs) frequently found in the plasma of patients with systemic lupus erythematosus (SLE) have been associated with thrombotic complications. Our aim was to clarify the roles in thrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as beta(2)-glycoprotein I (beta(2)-GPI), prothrombin, protein C, protein S, and annexin V. METHODS: We determined the prevalence of aPL Abs to various phospholipid-binding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 cases), and patients without complications (91 cases). The aPL Abs were measured by an ELISA system in which human plasma proteins (beta(2)-GPI, prothrombin, protein C, protein S, and annexin V) were immobilized on gamma-irradiated or plain polystyrene plates. RESULTS: All types of aPL Abs were frequently observed in the patients with SLE when gamma-irradiated polystyrene plates were used (51 of 168 cases positive for anti-beta(2)-GPI, 94 of 168 cases positive for anti-prothrombin, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive for anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plates were used. Multivariate analysis confirmed that both anti-beta(2)-GPI and anti-prothrombin Abs were significant risk factors for arterial thrombosis [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2-25 and 1.8-116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous thrombosis (OR, 30.4; CI, 3.3-281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V Abs (OR, 5.9; CI, 1.4-14.8). CONCLUSIONS: Patients with SLE frequently have some aPL Abs to beta(2)-GPI, prothrombin, protein C, protein S, and annexin V. Thrombotic complications in SLE may depend on the antigenic specificities of these Abs, alone or in combination.

Adolescent↗

[Postoperative chemotherapy with a novel oral anticancer drug composed of tegafur, gimeracil and oteracil potassium to curability C scirrhus type gastric cancer].

We report the a case of 60-year-old male whose final finding was curability C and stage IV scirrhus type gastric cancer because of N3, CY1 and DM (+) treated with a novel oral anticancer drug composed of tegafur (FT), Gimeracil (CDHP) and Oteracil Potassium (Oxo) in a molar ratio of 1:04:1 after operation. This drug was administered orally twice daily after meals at a dose of 80 mg/body/day. One cycle consisted of consecutive administration for 28 days and 14 days rest, and this treatment cycle was repeated twice. Postoperative abdominal CT showed swollen paraaortic lymph nodes regarded as metastasis. However, they were reduced after 1 cycle and remained so. The serum carcinoembryonic antigen (CEA) level had decreased after 1 cycle. The patient's performance status (PS) had also recovered without severe side effects. It was considered that this anticancer drug composed of FT, CDHP and Oxo was effective to scirrhus type gastric cancer and useful as an adjuvant chemotherapy in view of the patient's living quality.

Administration, Oral↗