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Biomedical subjects

H Wada

Publications and source records attributed to H Wada.

At least 163 records · Page 9Linked to original sources
PubMed2000

Evaluation of CMV/human herpes virus-6 positivity in bronchoalveolar lavage fluids as early detection of acute GVHD following BMT: evidence of a significant relationship.

We evaluated the relationship between CMV and human herpes virus-6 (HHV-6) reactivation and the incidence of grades 2 to 4 acute GVHD post BMT. Bronchoalveolar lavage fluid (BALF) samples extracted from 54 BMT recipients on post-BMT day 35 were analyzed by PCR for detection of CMV DNA, HHV-6 DNA and CMV plus HHV-6 DNA. CMV DNA was detected in 26 patients and 13 (50%) developed grades 2 to 4 acute GVHD. Of the 28 who were CMV negative, only six (21.4%) developed grades 2 to 4 acute GVHD. HHV-6 was detected in 18 patients, and 11 (61.1%) developed grades 2 to 4 acute GVHD. Of the 36 who were HHV-6 negative, only eight (22.2%) developed grades 2 to 4 acute GVHD. CMV and HHV-6 were detected in 13 patients, and eight (61.5%) developed grades 2 to 4 acute GVHD. Of the 23 who were negative for both CMV and HHV-6, only three (13%) developed grades 2 to 4 acute GVHD. In all experiments, the difference between the groups was significant (P<0.05, P<0.05 and P<0.01, respectively). We conclude that herpes virus infection, in particular CMV concurrent with HHV-6 reactivation, is predictive of moderate to severe acute GVHD.

Adolescent↗
PubMed2000

Complications after bone marrow transplantation are manifestations of systemic inflammatory response syndrome.

Bone marrow transplantation has been established as a useful treatment for various hematological disorders and is now performed widely, but the mortality rate is still high due to various complications. A clear therapeutic policy for such complications has not yet been established because of their complex nature. We investigated whether the major complications occurring after bone marrow transplantation could be classified as aspects of the systemic inflammatory response syndrome. Subjects were 10 patients who developed severe complications after bone marrow transplantation (graft-versus-host disease, thrombotic microangiopathy, respiratory disorders, and cytomegalovirus interstitial pneumonitis) and 16 patients without complications. Their symptoms, serum cytokines, and factors related to vascular endothelial damage were compared before and after transplantation. Whereas all 10 patients who developed complications had fever in the aplastic phase after transplantation, 15 of the 16 patients without complications remained afebrile (P < 0.001, t-test). When compared with the patients who did not develop complications, the patients with complications also showed significantly higher cytokine levels during the recovery phase after transplantation (P < 0.0001, t-test). Thus, the patients with complications developed fever in the aplastic phase and showed an increase of cytokines during the recovery phase, which triggered the occurrence of vascular endothelial damage shown by factors such as the thrombomodulin and plasminogen activator inhibitor type 1. This sequence of events corresponds with that occurring during systemic inflammatory response syndrome, so many of the complications of bone marrow transplantation can be considered as manifestations of this syndrome.

Adult↗
PubMed2000

Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation.

Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.

Adolescent↗
PubMed2000

The role of colour Doppler ultrasonography in detecting prostate cancer.

OBJECTIVE: To determine the usefulness of colour Doppler ultrasonography (CDUS) in detecting prostate cancer, by comparing CDUS with grey-scale transrectal ultrasonography (TRUS) and magnetic resonance imaging (MRI). PATIENTS AND METHODS: In all, 278 patients who underwent prostate biopsies because of an abnormal digital rectal examination, elevated prostate specific antigen levels, and/or abnormal TRUS between May 1998 and November 1999 were evaluated. The diagnostic accuracies of TRUS, CDUS, MRI and combinations of these imaging techniques in detecting prostate cancer were compared, based on the biopsy results. RESULTS: Carcinoma was detected in 233 of 1696 specimens, and 87 patients were diagnosed with prostate cancer. For each detected cancer site, the sensitivity of CDUS was lower than those of other imaging techniques, but CDUS had high a specificity and positive predictive value. The combination of grey-scale TRUS and CDUS or MRI improved the sensitivity and negative predictive value. The specificity and positive predictive value of the combination of grey-scale TRUS and MRI were less than those for grey-scale TRUS alone, while those for the combination of grey-scale TRUS and CDUS were higher than those for grey-scale TRUS alone. Five tumours were isoechoic but seen as hypervascular lesions with CDUS. CONCLUSION: CDUS provides information useful for detecting prostate cancer when used in combination with grey-scale TRUS, and should be included in the routine examination for prostate cancer.

Adenocarcinoma↗
PubMed2000

A multicenter trial of mizoribine compared with placebo in children with frequently relapsing nephrotic syndrome.

BACKGROUND: The use of corticosteroids or cytotoxic/immunosuppressive agents such as cyclophosphamide, chlorambucil, and cyclosporine for the treatment of frequently relapsing nephrotic syndrome (FRNS) is limited because of their adverse effects. This study was conducted to evaluate the efficacy and safety of mizoribine, a relatively new immunosuppressive drug developed in Japan, in children with FRNS. METHODS: A double-blind, placebo-controlled, multicenter trial was carried out in children, from 2 to 19 years old, with FRNS. At relapse, patients were treated with prednisolone. According to a dynamic allocation, mizoribine or a placebo was concurrently administered to each patient. Prednisolone was gradually tapered and discontinued within 12 weeks. The test drug was maintained for 48 weeks. The primary end point was the relapse rate (the total number of relapses/the total treatment days for all patients). Analyses were performed according to the intention-to-treat principle. RESULTS: The primary analysis was conducted on 99 mizoribine- and 98 placebo-treated patients. The relapse rate was lower in the mizoribine group than in the placebo group (0.0055 vs. 0.0067; ratio 0.81, 95% CI, 0.61 to 1.05, P = 0.12). The hazard ratio of the cumulative remission rate between the two groups was 0.79 (95% CI, 0. 57 to 1.08). In the subgroups consisting of patients 10 years old or younger, the relapse rate ratio between the mizoribine subgroup (54 patients) and the placebo subgroup (57 patients) was 0.66 (95% CI, 0. 44 to 0.94, P = 0.017). The hazard ratio of the cumulative remission rate between the two subgroups was 0.56 (95% CI, 0.37 to 0.85, P = 0. 007). Hyperuricemia was the most common adverse event with mizoribine (16%), but was transient. CONCLUSIONS: Compared with the placebo, mizoribine significantly decreased the relapse rate and prolonged the remission period in the subgroup consisting of patients 10 years old or younger. This drug may be useful in young children with FRNS who generally relapse more frequently than older children.

Adolescent↗
PubMed2000

Cerebral tissue oxygen saturation during percutaneous cardiopulmonary support in a canine model of respiratory failure.

Percutaneous cardiopulmonary support (PCPS) has come to be applied for cardiopulmonary resuscitation and in the management of severe respiratory failure as well as severe heart failure. We investigated cerebral tissue oxygen saturation during PCPS in a canine model of respiratory failure using near-infrared spectroscopy. Animals were mechanically ventilated with 10% oxygen to make a respiratory failure model. Perfusion with PCPS was performed via the left femoral artery and switched to that via the right axillary artery. Cerebral tissue oxygen saturation was 54.2 +/- 3.4% during PCPS via the femoral artery and was 82.3 +/- 4.6% during PCPS via the axillary artery (p = 0.001). Hepatic tissue oxygen saturation was not significantly different. LV dP/dt max increased significantly after switching to the axillary blood supply (p = 0.001). Conventional PCPS may not have the capability of supporting cerebral circulation under severe respiratory failure without organic heart disease.

Analysis of Variance↗
PubMed2000

Eccentric roller type total artificial heart creating interatrial shunt.

Creating an interatrial shunt to achieve left-right flow balance and modification of the blood chambers to improve the basic performance of the device were performed in developing an eccentric roller type total artificial heart (ERTAH). Smaller blood chambers reduce friction loss and increase durability and energy efficiency. We changed the left blood chamber volume of 60 ml to 40 ml and the right blood chamber volume of 53 ml to 35 ml compared with previous types. Designs of inlet and outlet ports were modified to prevent backflow. In the mock circulatory system, redesigning the blood chambers resulted in a 20% increase in energy efficiency, about a two-fold increase of cardiac output and improved durability compared to the previous type. In an animal experiment, the ERTAH operated at a driving rate of 160 rpm with a left flow rate of 6.0 L/min and a right flow rate of 5.4 L/min. Interatrial shunt flow rate was 250-400 ml/min.

Animals↗
PubMed2000

Diagnosis of disseminated intravascular coagulation by hemostatic molecular markers.

In the present study, the positive rate of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), soluble fibrin monomer (sFM), and D-dimer for the diagnosis of disseminated intravascular coagulation (DIC) was evaluated. The study comprised 307 patients with DIC, 123 with pre-DIC, and 121 with non-DIC. Plasma levels of TAT, PPIC, sFM, and D-dimer were significantly higher in DIC and pre-DIC patients than in non-DIC patients. In DIC patients, the positive rate of sFM was high and that of D-dimer was low; the positive rate of PPIC was higher in patients with hematopoietic malignancy than in those without this disease. In pre-DIC patients, the positive rate of all markers was low (<0.16), and the positive rate of PPIC was relatively high. In non-DIC patients, the positive rate of all hemostatic markers was low (<0.16), that of sFM being the lowest. Scoring the positive rate of TAT, PPIC, and sFM disclosed the following results: 72% of DIC patients had three or more points, 17.6% of pre-DIC patients had three or more points, and almost all (96.6%) non-DIC patients had two or less points. Scoring the positive rate of TAT, PPIC, and D-dimer disclosed the following results: 52.9% of DIC patients and 27.4% of pre-DIC patients had three or more points and almost all (96.7%) non-DIC patients had 2 or less points. These data suggest that the combination of TAT, PPIC, and sFM is useful for making the diagnosis of DIC.

Antifibrinolytic Agents↗
PubMed2000

Study of cardiovascular risk factors and hemostatic molecular markers in elderly persons.

In this study, plasma concentrations of hemostatic molecular markers were investigated in 118 elderly persons with normal renal function (aged 65 to 97 years) who could manage their activities of daily living (ADL) by themselves, to find a strategy for conservation or elevation of ADL and quality of life (QOL). In all subjects, the frequency by which hemostatic markers exceeded their upper limit of normal range was 35.9% for thrombin-antithrombin HI complex (> or = 3.7 ng/ml), 38.3% for soluble fibrin monomer (> or = 4.0 microg/ml), 41.8% for D-dimer (> or = 1.0 microg/ml), 49.0% for plasmin-alpha2 plasmin inhibitor complex (> or = 1.0 microg/ml), and 53.7% for thrombomodulin (> or = 20 ng/ml). The mean plasma levels of these markers were slightly higher than the upper limit of their normal range. These markers were also investigated in samples of patients with and without cardiovascular risk factors and with and without cardiovascular diseases (ischemic heart disease and/or cerebral infarction). Furthermore, the results were analyzed in relationships between cardiovascular disease and cardiovascular risk factor or aging. The findings suggest that aging exerts a stronger influence on plasma levels of these hemostatic molecular markers than the presence of cardiovascular risk factors and cardiovascular diseases. From the viewpoint for conservation or elevation of ADL and QOL in elderly persons, also other factor, such as drug intake, lifestyle, aging, and so on, must be considered to clarify the relationship between the plasma levels of the hemostatic molecular markers and cardiovascular risk factors or cardiovascular diseases.

Aged↗
PubMed2000

ISI/INR system in Japan: experience from simultaneous measurement of the same plasma at four different laboratories.

In 1984, the Scientific and Standardization Committee (formerly ICTH) recommended the use of the International Sensitivity Index and International Normalized Ratio (ISI/INR) System for the monitoring of oral anticoagulant therapy. This system was introduced because the sensitivity of thromboplastin reagents used for the measurement of prothrombin time (PT) was widely different and comparison among hospitals employing different reagents was virtually impossible. In this study, we simultaneously measured the plasma from 7 patients with warfarin therapy at 4 different institutions for PT seconds, PT-INR, thrombotest (TT) seconds and TT-INR. The comparison between these laboratories revealed clinically important variances between the 4 laboratories even when PT was converted to PT-INR. Laboratory 1 and laboratory 3 were using the same thromboplastin reagents for the measurement of PT. The PT (seconds) in both laboratories showed similar numbers, but when they converted into INR, the variances were significant (maximum coefficient of variance 10.44). We investigated the reason why these differences occurred and found that the PT seconds (11.40) for normal control at laboratory 3 were somewhat larger than those of other laboratories. If we assume that PT-INR is identical to TT-INR, the estimated PT (second) for normal control at laboratory 3 can be calculated from TT-INR, and was found to be 10.56 +/- 0.10 seconds. This was nearly the same as the one that was used at laboratory 1. In conclusion, there still exist some difficulties that must be overcome before the ISI/INR system can be used reliably, and we suggest attention be given to the PT seconds used as normal control plasma.

Adult↗
PubMed2000

Increased hemostatic molecular markers in patients undergoing anticoagulant therapy.

We evaluated several molecular markers of hemostasis in 92 patients with hypercoagulable states treated with anticoagulant therapy. In all patients, the average values of the international normalized ratio (INR) were 1.70 +/- 0.50; this increase in INR was not, however, significant in patients under thrombotest (TT) monitoring. There were no thrombotic or severe bleeding complications in these patients during a period of 27 months. Plasma levels of thrombin-antithrombin complex (TAT), plasmin-plasmin inhibitor complex (PPIC), D-dimer, and soluble fibrin monomer (sFM) were slightly increased, suggesting that anticoagulant therapy was not completely effective in our Japanese patients based on the values of the TT. The INR was negatively correlated with TT, protein C, and protein S and particularly with TT between 10 and 80%. The range of TT was not correlated with the plasma level of TAT, PPIC, D-dimer, or sFM, but the range of INR was correlated with the plasma level of TAT, D-dimer, and sFM. The percentage of TAT, D-dimer, and sFM within normal range was significantly lower in patients with high INR. These findings show that INR is better than TT for the monitoring of warfarin therapy and that the therapeutic values of INR during the anticoagulant therapy should be > 1.7 in Japanese patients.

Adult↗
PubMed2000

Redox regulation by thioredoxin superfamily; protection against oxidative stress and aging.

Thioredoxin (TRX) is a 12 kD protein with redox-active dithiol in the active site; -Cys-Gly-Pro-Cys-. We originally cloned human TRX as adult T cell leukemia derived factor (ADF) produced by HTLV-I transformed cells. TRX and related molecules maintain a cellular reducing enviroment, working in concert with the glutathione system. Physiologically, TRX has cytoprotective effects against oxidative stress. TRX promotes DNA binding of transcription factors such as NF-kB, AP-1, p53, and PEBP-2. The TRX superfamily, including thioredoxin-2 (mitochondrial thioredoxin) and glutaredoxin, are involved in biologically important phenomena via the redox-regulating system. Thioredoxin-binding protein-2, which we recently identified by a yeast two-hybrid system, is a type of endogenous modulator of TRX activity. TRX is secreted from the cells and exhibits cytokine-like and chemokine-like activities. Redox regulation by TRX plays a crucial role in biological responses against oxidative stress.

Aging↗
PubMed2000

Immunohistochemical localization of telomerase hTERT protein and analysis of clonality in multifocal vulvar intraepithelial neoplasia.

Vulvar intraepithelial neoplasias (VINs) are potentially premalignant lesions of the squamous mucosa. The immunohistochemical distribution of the catalytic protein subunit of telomerase (hTERT) and the patterns of X chromosome inactivation were investigated as markers of neoplasia in samples from a patient with multifocal and diffuse VIN. hTERT nuclear staining in VIN correlated with squamous maturation and the degree of nuclear atypia. Normal mucosa revealed faint nuclear staining of parabasal cells and lower intermediate layer squamous cells. Monoclonal composition was demonstrated in 0 of 3 samples of VIN1, 2 of 3 samples of VIN2, and 13 of 13 samples of VIN3. The patterns of X chromosome inactivation indicated intramucosal extension and multifocal origin of individual lesions. Five samples of histologically normal vulvar squamous epithelium revealed a random pattern of X chromosome inactivation, consistent with polyclonal composition. All 19 samples from 9 lesions contained human papillomavirus (HPV)-16 sequences. Neither mutations in the p53 tumor suppressor gene or K-ras oncogenes nor loss of heterozygosity at 7 chromosomal loci were detected in any of the 19 samples of VIN. These results demonstrate that HPV-associated VIN may result from multifocal and diffuse 2-dimensional intraepithelial expansion of an immortalized monoclonal cell population.

Carcinoma in Situ↗
PubMed2000

A detailed linkage map of medaka, Oryzias latipes: comparative genomics and genome evolution.

We mapped 633 markers (488 AFLPs, 28 RAPDs, 34 IRSs, 75 ESTs, 4 STSs, and 4 phenotypic markers) for the Medaka Oryzias latipes, a teleost fish of the order Beloniformes. Linkage was determined using a reference typing DNA panel from 39 cell lines derived from backcross progeny. This panel provided unlimited DNA for the accumulation of mapping data. The total map length of Medaka was 1354.5 cM and 24 linkage groups were detected, corresponding to the haploid chromosome number of the organism. Thirteen to 49 markers for each linkage group were obtained. Conserved synteny between Medaka and zebrafish was observed for 2 independent linkage groups. Unlike zebrafish, however, the Medaka linkage map showed obvious restriction of recombination on the linkage group containing the male-determining region (Y) locus compared to the autosomal chromosomes.

Animals↗
PubMed2000

Highly increased plasma concentrations of the nicked form of beta(2) glycoprotein I in patients with leukemia and with lupus anticoagulant: measurement with a monoclonal antibody specific for a nicked form of domain V.

beta(2)-Glycoprotein I (beta(2)GPI) consists of five tandem repeated domains (I, II, III, IV, and V). The nicked form of beta(2)GPI (N-beta(2)GPI ) which was cleaved by plasmin in vitro at Lys 317-Thr 318 in domain V, showed reduced affinity for the negatively charged phospholipids, especially cardiolipin (CL). Recently, the N-beta(2)GPI was detected in the plasma of patients with disseminated intravascular coagulation syndrome (DIC) by an immunological method. In the present study, we prepared monoclonal antibodies for the nicked form, and demonstrated that the concentrations of this form of beta(2)GPI, which were analyzed by a sandwich ELISA using two specially prepared monoclonal antibodies, were significantly increased in the plasma of patients with leukemia (n = 51, mean +/- SD: 162.0 +/- 118.3 ng/ml) and with lupus anticoagulant (LA) (n =40, mean +/- SD: 3,041.5 +/- 16,579.7 ng/ml), compared to the normals (n = 33, mean +/- SD: 1.04 +/- 1.54 ng/ml). We found a significant correlation between the concentrations of N-beta(2)GPI and those of typical molecular markers for a fibrinolytic state such as plasmin-alpha(2) plasmin inhibitor complex (PIC) and D-dimer in patients with leukemia, but not in patients with LA. These results suggested that the generation of N-beta(2)GPI was caused by plasmin in the patients with leukemia, and by unknown proteases in the patients with LA. In the patients with LA, the levels of N-beta(2)GPI tended to be higher in those without thrombosis than in those with thrombosis.

Antibodies, Monoclonal↗
PubMed2000

Control of antibody-antigen interaction using anion-induced conformational change in antigen peptide.

The binding of a monoclonal antibody to an epitope peptide was controlled by the conformational change of the epitope peptide induced by anions. We synthesized peptides in which the epitope sequence DTYRYI for the monoclonal antibody AU1 is located between amphiphilic peptides (KKLL)n and (LLKK)n. In the absence of an appropriate anion, the peptide was in a random coil state and the epitope was linear. In contrast, in the presence of an appropriate anion, the peptide exhibited an anti-parallel alpha-helical structure and the epitope was subsequently 'bent'. In the presence of 41 microM triphosphate, the association constant between the antibody and the peptide was decreased by one order of magnitude in the case of n = 3 and at least three orders of magnitude in the case of n = 4 or 5. Oligo-DNAs, as anions, dissociated the antibody-peptide complex, whereas triphosphate did not. The DNA concentrations required for 50% dissociation of the antibody-peptide complex at pH 7.5 were 4x10(-8), 1x10(-7) and 6x10(-6) M for decamer, octamer and hexamer DNA, respectively.

Amino Acid Sequence↗