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Biomedical subjects

T Komiya

Publications and source records attributed to T Komiya.

At least 73 records · Page 4Linked to original sources

Protection against verocytotoxin in mice induced by liposome-coupled verocytotoxin.

Purified verocytotoxins (VTs), VT1 and VT2, were coupled to liposomes via glutaraldehyde. During the coupling procedure, both VT1 and VT2 were detoxified. Intraperitoneal injection in BALB/c mice with either VT1-liposome or VT2-liposome induced a substantial amount of anti-VT1 or anti-VT2 IgG antibody production, respectively. Mice immunized with VT2-liposome were protected against intravenous challenge with a lethal dose of VT2 and the degree of protection correlated well with the amount of IgG induced against VT2. Although VT1-liposome failed to induce protection against VT1, the decrease of the body weight observed after the toxin challenge correlated inversely with the amount of anti-VT1 IgG induced, suggesting that VT1 neutralizing antibody was present in VT1-liposome-immune mice. In addition, VT-liposome conjugate induced no detectable anti-VT IgE antibody production. These results demonstrate the potential ability of VT-liposome conjugates for the production of VT vaccine which induces protection against VTs.

Animals↗

Inhibitory effects of persimmon (Diospyros kaki) extract and related polyphenol compounds on growth of human lymphoid leukemia cells.

We have investigated the effects of persimmon (Diospyros kaki) extract (PS) and related polyphenol compounds such as catechin (C), epicatechin (EC), epicatechingallate (ECG), epigallocatechin (EGC), and epigallocatechingallate (EGCG) on the growth of human lymphoid leukemia Molt 4B cells. We found that PS, ECG, EGC, and EGCG strongly inhibited the growth of the cells in a dose-dependent manner, while C and EC inhibited the growth of the cells only moderately. Ornithine decarboxylase (ODC), a rate-limiting enzyme of polyamine biosynthesis, was inhibited by 10-20% by these polyphenol compounds. The morphology of the Molt 4B cells indicated severe damage 3 days after treatment with PS, ECG, EGC, and EGCG. Irregular shape of the cells and DNA fragmentation were observed in PS, ECG, EGC, or EGCG-treated cells. These results suggest that PS, ECG, EGC, and EGCG induce apoptosis (programmed cell death) of Molt 4B cells.

Antineoplastic Agents↗

[Histological study of micrognathic development in mouse fetus induced by 3,3-dimethyl-1-phenyltriazene].

The purpose of this study was to investigate the influence of 3,3-dimethyl-1-phenyltriazene (DMPT) on development of craniofacial structures in mouse fetus. (1) Pregnant C57BL/6 mice were treated with 30 mg/kg DMPT injection on days 10.5 approximately 13.5 of gestation. The fetuses were analyzed on day 15.0. The incidence of micrognathia was formed 100% in the treated group on days 10.5 and 11.0, and then decreased remarkably after day 11.5. This result suggested that the critical period of micrognathic development is days 10.5 approximately 11.0. (2) The fetuses, injected 30 mg/kg DMPT on day 10.5, were sacrificed on days 11.0 approximately 18.0. Their heads were used for the following histomorphological analyses: 1. clearing and Alcian blue-alizarin red double staining and 2. lateral graphic reconstruction using serial frontal sections. Dysmorphology of the anterior portion of Meckel's and nasal septal cartilage became evident after day 13.0, however, nasal capsule cartilage was hardly affected. It was concluded that hypoplastic Meckel's cartilage, caused by the administration of DMPT, induced mandibular dysmorphogenesis.

Animals↗

A comparison of young and aged populations for the diphtheria and tetanus antitoxin titers in Japan.

The antitoxin levels for diphtheria and tetanus were measured with samples of a young group immunized with diphtheria-tetanus-acellular pertussis combined vaccine and those of an aged group, members of which had not received vaccination in their youth. In the young group members of which had already received basic immunization with diphtheria-tetanus-acellular pertussis combined vaccine, the levels of both antitoxins rose well after injection at 11 to 12 years old with diphtheria-tetanus combined toxoids and remained high until 20 years of age. In the aged group, more than 80% showed antitoxin levels above 0.01 u/ml for diphtheria, while all had levels below that for tetanus, except three persons with confirmed tetanus immunization history. Maintenance of the protective antitoxin levels in the population by vaccination is necessary to prevent outbreaks of infection among unvaccinated or only partially immunized persons.

Adolescent↗

[A case of extracardiac noncoronary sinus Valsalva aneurysm associated with aortic regugitation].

A case of extracardiac noncoronary sinus Valsalva aneurysm was reported. A 11-year-old male with history of mild AR was admitted to the hospital due to severe AR. Echocardiography revealed that the severe AR and an aneurysm in the posterior part of the ascending aorta. Angiography revealed that the origin of the aneurysm was noncoronary sinus. Operative findings showed that the aneurysm sized 23 mm by 25 mm was an extracardiac type which grew posteroinferiorily at the left side of noncoronary sinus and that the dilation. Neither aortic valve nor the aortic route showed degenerative change. The ptosis of the valvular ring due to aneurysmal dilation of the noncoronary sinus caused AR. Then, valve repair composed by commissuroplasty and commissural suspension was carried out. And intraluminal patch closure technique in which the longitudinal diameter of patch was half of that of the aneurysm was effective on suspension of the valvular ring. Postoperative echocardiography showed decreasing of AR.

Aortic Aneurysm↗

[Early repair of ventricular septal rupture in patients over 80 years of age: infarction exclusion technique].

Since 1994, three patients more than 80 years of age underwent early repair of ventricular septal rupture complicating acute myocardial infarction at our hospital. The infarction exclusion technique introduced by David and Komeda was employed. Average aortic clamp time, cardiopulmonary bypass time and operation time were 83 minutes, 129 minutes and 228 minutes, respectively. No hemostatic suture were required to the left ventricular suture line. All patients survived. One patient with posterior ventricular septal rupture had residual shunt and necessitated transient hemodialysis but recovered. Thus, the infarction exclusion technique seems to be useful in the elderly with unfavorable tissue fragility.

Aged↗

[Hypercoagulable state in Duchenne muscular dystrophy].

Pulmonary and cerebral infarctions have come to be noticed as life-threatening complications of Duchenne muscular dystrophy (DMD). In order to elucidate the underlying mechanism of hypercoagulable state, was studied following markers of coagulation and fiblinolysis in 69 DMD and 50 control patients showing no signs of thrombosis: prothrombin time, activated partial thrombin time, thrombotest, fibrinogen, fibrinogen degradation product, thrombin-antithrombin III complex (TAT), alpha 2-plasmin inhibitor plasmin complex (PIC), D-dimer, protein C activity, protein S, antithrombin III, XII factor, thrombomodulin and plasminogen activity. 66 out of 69 patients (96%) showed abnormal results in more than one of these studies, among which abnormally low thrombotest (78%), high TAT (61%) and high PIC (40.3%), were very frequently observed. The results were not correlated to the age, the activity of daily living and the respiratory of cardiac functions. Significantly smaller number of the control patients suffering from other neuromuscular diseases showed abnormal results, while the ambulatory DMD patients not infrequently showed hypercoagulable state. These results strongly suggest that unknown inherent factor(s) as well as inevitable immobilization and cardiac dysfunction play(s) an important role in the development of hypercoagulable state in this intractable disorder.

Adolescent↗

[The significance of heparin concentration measurement during cardiopulmonary bypass--effect of heparin-coated circuit during normothermic bypass].

Recently, use of heparin-coated circuits during normothermic cardiopulmonary bypass has become a trend in cardiovascular surgery. In light of this, heparin administration protocols during bypass should be reevaluated. In twenty patients who underwent cardiac surgery using a heparin-coated circuit under normothermia, heparin concentration was measured with Hepcon/HMS. Before initiating bypass, 300 IU/kg of heparin was administered with additional heparin to maintain activated clotting time (ACT) at more than 400 seconds. The heparin dose response (HDR) was measured before heparin administration. HDR is a heparin concentration calculated to correspond to an ACT of 480 seconds. As an index of heparin control during bypass, average heparin concentration/HDR (HC/HDR) was calculated. HC/HDR was correlated with Fibrinogen degradation products E (R = -0.52). D dimer (R = -0.45). Thrombin antithrombin complex (R = -0.54). Antithrombin III (R = 0.50) and platelet number (R = 0.44), but not with 24-hour postoperative blood loss. In conclusion, even when using a heparin-coated circuit plasma coagulation activity was not sufficiently suppressed by use of a conventional ACT monitoring protocol during normothermic bypass. Therefore, the maintenance of HC/HDR at a higher level may be indicated.

Adolescent↗

p21 expression as a predictor for favorable prognosis in squamous cell carcinoma of the lung.

Although p21 WAF1/Cip1 expression has been detected immunohistochemically in non-small cell lung cancer (NSCLC), the associations between p21 expression and clinical characteristics are unknown. To determine the association between p21 expression and clinical features, p21 expression was immunohistochemically analyzed in paraffin-embedded tumor samples from 137 patients with curatively resected NSCLC. p21 expression, indicating normal p21 function, was detected in 48 (35.0%) of the 137 patients with curatively resected NSCLC and was detected more frequently in patients with stage I or II disease (40.2%) than in those with stage IIIA disease (22.5%; P = 0.0483). There was no difference in the positive rate between squamous cell carcinoma [SCC; 15 of 48 (31.3%)] and adenocarcinoma [30 of 77 (39.0%)]. For SCC, patients with tumors expressing p21 survived longer than did those with tumors negative for p21 expression; however, the corresponding survival time was not significant for adenocarcinoma. On the other hand, p53 expression, detected in 58 (42.3%) of these patients, did not act as any predictor for prognosis in either SCC or adenocarcinoma. Our findings suggest that the presence of p21 expression is associated with favorable prognosis in SCC and may be useful in obtaining candidates for adjuvant therapies from among patients with SCC.

Adenocarcinoma↗

Protein import into mammalian mitochondria. Characterization of the intermediates along the import pathway of the precursor into the matrix.

We have characterized several intermediates in the mitochondrial import stimulation factor (MSF)-dependent import into mammalian mitochondria of a matrix-targeted precursor, preadrenodoxin (pAd). In the first step, pAd docks onto the 37-kDa protein of the outer membrane (OM37) as a complex with MSF (stage I intermediate). It is then transferred to the import pore of OM in the presence of ATP, but in the absence of Deltapsi across the inner membrane (IM), to form stage II intermediate. Depletion of matrix ATP in the presence of both extramitochondrial ATP and Deltapsi induces accumulation of stage III intermediate, which is a mixture of the precursor with different intramitochondrial localizations: the precursor whose presequence had crossed either OM (IIIa) or both OM and IM (IIIb), but with a bulk portion remaining exposed to the cytosol and the precursor whose presequence had crossed both membranes, but with a residual portion staying within the intermembrane space (IIIc). These intermediates are on the correct import pathway and are characteristic in their protease accessibility, salt extractability, and antibody accessibility, as well as in their energy requirement for the chase reaction.

14-3-3 Proteins↗

Cytoplasmic chaperones determine the targeting pathway of precursor proteins to mitochondria.

Two ATP-dependent cytosolic chaperones, mitochondrial import stimulation factor (MSF) and hsp70, are known to be involved in the import of precursor proteins into mitochondria. Hsp70 generally recognizes unfolded proteins, while MSF specifically recognizes mitochondrial precursor proteins and targets them to mitochondria in a NEM-sensitive manner. Here we analyzed the relative contribution of these chaperones in the import process and confirmed that the precursor proteins are targeted to mitochondria via two distinct pathways: one requiring MSF and the other requiring hsp70. Both pathways depend on distinct proteinaceous components of the outer mitochondrial membrane. The MSF-dependent pathway is NEM-sensitive and requires the hydrolysis of extra-mitochondrial ATP for the release of MSF from the mitochondrial import receptor, whereas the hsp70-dependent pathway is NEM-sensitive and does not require extra-mitochondrial ATP. The NEM-insensitive, hsp70-dependent import became NEM-sensitive depending on the amount of MSF added. The relative importance of the two pathways appears to be determined by the affinities of MSF and hsp70 for the precursor proteins.

14-3-3 Proteins↗

Truncus arteriosus repair: influence of techniques of right ventricular outflow tract reconstruction.

Fifty-six consecutive patients underwent total correction of truncus arteriosus. Median age at repair was 41 days, with a range of 2 days to 8 months. In 71% the operation was done in the first 2 months of life. Nine patients had complex forms of truncus and 11 patients had aortic insufficiency. The truncal aortic root was transected, which provides a clear exposure of the coronary ostia. The aorta was reconstructed by direct end-to-end anastomosis, and the truncal valve was preserved in every case. Several different techniques were used for pulmonary reconstruction, including three types of anatomic reconstruction of the pulmonary valve with a trisigmoid leaflet system and two types of nonanatomic reconstruction. The anatomic techniques included use of 33 Dacron valved conduits, eight homograft valved conduits, and one porcine aortic root bioprosthesis. The nonanatomic reconstructions included direct anastomosis to the right ventricle in nine patients and insertion of autologous pericardial valved conduits in five. The hospital mortality was 16% (9/56; 95% confidence limits, 2% to 30%). Multivariate analysis outlines two independent incremental risk factors for hospital death: nonanatomic pulmonary valve reconstruction techniques and age younger than 1 month. The hospital mortality was 7.1% in the group with anatomic pulmonary valve reconstruction versus 43% in the group with nonanatomic pulmonary valve reconstruction (p = 0.015). The hospital mortality was 5.7% in those older than 1 month versus 33% in those younger than 1 month of age (p = 0.04). There were two late deaths. The actuarial freedom from reoperation and angioplasty at 7 years was 100% for patients receiving pericardial conduits, 80% for those undergoing direct anastomosis, 77% for those receiving Dacron conduits, and only 43% for those receiving homografts (p = 0.02). In conclusion, anatomic reconstruction of the pulmonary valve seems important at the time of the operation, age younger than 1 month remains an incremental risk factor, and the truncal valve can be preserved.

Age Factors↗

Pro-gastrin-releasing peptide (31-98) as a tumour marker of small-cell lung cancer: comparative evaluation with neuron-specific enolase.

We attempted to clarify whether serum levels of a carboxy-terminal fragment of ProGRP, ProGRP(31-98), could serve as a more accurate tumour marker in patients with SCLC than neuron-specific enolase (NSE). ProGRP(31-98) and NSE were measured retrospectively in 101 newly diagnosed untreated patients with SCLC, 111 with non-small-cell lung cancer (NSCLC) and 114 patients with non-malignant lung diseases. ProGRP(31-98) and NSE levels were determined using a sandwich enzyme-linked immunosorbent assay. Sensitivity in SCLC patients was 72.3% for ProGRP(31-98) and 62.4% for NSE. Comparing the area under curve (AUC) of 'receiver operator characteristics' of ProGRP(31-98) with that of NSE, ProGRP(31-98) was the more powerful marker in the diagnosis of SCLC (P = 0.0001). Serum levels of ProGRP(31-98) were higher in the 40 patients with extensive disease than in the 61 patients with limited disease (P = 0.0082). ProGRP(31-98) was significantly higher in patients with pure small-cell carcinoma than in patients with mixed small-cell/large-cell carcinoma (P = 0.02). In serial measurement in 16 patients responding to treatment, a high degree of correlation was noted between the decrease in serum ProGRP(31-98) levels and clinical response during the second week after treatment (P = 0.0045). These results indicate that the determination of serum ProGRP(31-98) levels plays an important role in the diagnosis and treatment of SCLC patients.

Biomarkers, Tumor↗

Conversion of glutathione into cadystins and their analogs catalyzed by carboxypeptidase Y.

Cadystins induced in a fission yeast treated with Cd2+ are the higher homologs of glutathione. In the present work, glutathione was incubated with Carboxypeptidase Y at a high substrate concentration. The reaction afforded not only the degraded product, but also cadystins and their analogs. A possible transformation pathway for glutathione by this enzyme is proposed.

Amino Acid Sequence↗

Isolation and partial structure of a unique lipophilic peptide, VAP peptide, from the heads of male silkworm moths.

A new lipophilic peptide was isolated from the MeOH-CH2Cl2 extract of adult heads of the male silkworm, Bombyx mori, by monitoring the diapause egg-inducing activity. Partial amino acid sequencing (1-55) revealed this peptide to be a unique type having a high content of lipophilic amino acids, Val, Ala, and Pro, and many repeating sequences. The compound was thus named VAP peptide.

Amino Acid Sequence↗

Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. I. Taxonomy, fermentation, isolation and biological activities.

Selective growth inhibition against IL-6 dependent cells was detected in fermentation extracts of a fungal strain FO-4649 which was characterized as Sporothrix species. An active metabolite (1) termed chlovalicin was isolated together with ovalicin and two other ovalicin derivatives (compounds 3 and 4). Chlovalicin, a ovalicin derivative with a chlorinated methylene moiety at the C-1 position of the cyclohexane ring, dose-dependently inhibited the growth of IL-6 dependent MH60 cells (IC50, 7.5 microM) in the presence of 0.2 U/ml IL-6 and, to a lesser extent, the growth of B16 melanoma cells (IC50, 38 microM). Among the other three compounds, only ovalicin showed inhibitory activity (IC50, 27 microM) against MH60 cells. These four compounds did not show any antimicrobial activity at a concentration of 1000 micrograms/ml.

Animals↗

Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. II. Physicochemical properties and structural elucidation.

A new growth inhibitor of IL-6 responsive MH60 cells, chlovalicin (MW; 332, C16H25O5Cl), was found in cultures of Sporothrix sp. FO-4649, together with a known sesquiterpene, ovalicin. The structure of chlovalicin was elucidated by spectroscopic methods. Chlovalicin possesses a chlorinated methylene moiety at the C-1 position, and it corresponds to halogenated products derived from the epoxide ring attached to the C-1 position of ovalicin. The absolute configuration of chlovalicin was clarified as 1S, 2R, 3S, 1'S, 2'R by chemical transformation from ovalicin.

Anti-Bacterial Agents↗

[Chemotherapy of small cell lung cancer].

Chemotherapy of small cell lung cancer is reviewed. Combination chemotherapy with cisplatin/etoposide (PE) or CAV (cyclophosphamide, adriamycin and vincristine) alternating with PE was established as standard regimens. Dose intensive chemotherapy, such as weekly regimens or using G-CSF, is being investigated. In patients with limited disease (LD), combined modality treatment is proven to produce favorable results, but the best sequence or fractionation of thoracic radiotherapy is unknown. More progress in the treatment of small cell lung cancer is expected.

Antineoplastic Combined Chemotherapy Protocols↗