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Biomedical subjects

T Okamoto

Publications and source records attributed to T Okamoto.

At least 55 records · Page 3Linked to original sources

Self-regeneration of a Pd-perovskite catalyst for automotive emissions control.

Catalytic converters are widely used to reduce the amounts of nitrogen oxides, carbon monoxide and unburned hydrocarbons in automotive emissions. The catalysts are finely divided precious-metal particles dispersed on a solid support. During vehicle use, the converter is exposed to heat, which causes the metal particles to agglomerate and grow, and their overall surface area to decrease. As a result, catalyst activity deteriorates. The problem has been exacerbated in recent years by the trend to install catalytic converters closer to the engine, which ensures immediate activation of the catalyst on engine start-up, but also places demanding requirements on the catalyst's heat resistance. Conventional catalyst systems thus incorporate a sufficient excess of precious metal to guarantee continuous catalytic activity for vehicle use over 50,000 miles (80,000 km). Here we use X-ray diffraction and absorption to show that LaFe(0.57)Co(0.38)Pd(0.05)O(3), one of the perovskite-based catalysts investigated for catalytic converter applications since the early 1970s, retains its high metal dispersion owing to structural responses to the fluctuations in exhaust-gas composition that occur in state-of-the-art petrol engines. We find that as the catalyst is cycled between oxidative and reductive atmospheres typically encountered in exhaust gas, palladium (Pd) reversibly moves into and out of the perovskite lattice. This movement appears to suppress the growth of metallic Pd particles, and hence explains the retention of high catalyst activity during long-term use and ageing.

Journal Article↗

Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells.

Cimetidine has been shown to have beneficial effects in colorectal cancer patients. In this study, a total of 64 colorectal cancer patients who received curative operation were examined for the effects of cimetidine treatment on survival and recurrence. The cimetidine group was given 800 mg day(-1) of cimetidine orally together with 200 mg day(-1) of 5-fluorouracil, while the control group received 5-fluorouracil alone. The treatment was initiated 2 weeks after the operation and terminated after 1 year. Robust beneficial effects of cimetidine were noted: the 10-year survival rate of the cimetidine group was 84.6% whereas that of control group was 49.8% (P<0.0001). According to our previous observations that cimetidine blocked the expression of E-selectin on vascular endothelium and inhibited the adhesion of cancer cells to the endothelium, we have further stratified the patients according to the expression levels of sialyl Lewis antigens X (sL(x)) and A (sL(a)). We found that cimetidine treatment was particularly effective in patients whose tumour had higher sL(x) and sL(a) antigen levels. For example, the 10-year cumulative survival rate of the cimetidine group with higher CSLEX staining, recognizing sL(x), of tumours was 95.5%, whereas that of control group was 35.1% (P=0.0001). In contrast, in the group of patients with no or low levels CSLEX staining, cimetidine did not show significant beneficial effect (the 10-year survival rate of the cimetidine group was 70.0% and that of control group was 85.7% (P=n.s.)). These results clearly indicate that cimetidine treatment dramatically improved survival in colorectal cancer patients with tumour cells expressing high levels of sL(x) and sL(a).

Administration, Oral↗

Expression and localization of nm23-H1 in the human placenta.

The involvement of the nm23 gene, initially documented as a putative metastasis-suppressor gene, in normal development and differentiation has been supported by several investigations. To date, however, localization and expression pattern of nm23 in the human placenta has not been determined. In the present study, the expression of nm23-H1 was examined by Northern blot and immunohistochemical analyses in human placentas from various stages of gestation. In first trimester placenta, the villous cytotrophoblast and the extravillous trophoblast exhibited strong cytoplasmic staining for nm23-H1. In second trimester and term placentas, the few cytotrophoblasts present showed less intense staining than those in first trimester placenta. Northern blot analysis demonstrated a progressive decrease in nm23-H1 gene expression with advancing gestational age, which is consistent with the results obtained by immunohistochemistry. These findings suggest that nm23-H1 is involved in the differentiation process of the trophoblast, and high levels of nm23-H1 expression seem to reflect the proliferating, less differentiated state of that reserve.

Blotting, Northern↗

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome following allogeneic bone marrow transplantation.

We monitored the levels of various cytokines and chemokines, as well as an adhesion molecule and factors related to vascular endothelial damage, in three patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation. Measurements were done at the onset of this condition and during plasma exchange for treatment. At the onset of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome, the levels of interleukin-8, thrombomodulin, and plasminogen activator inhibitor-1 were all markedly increased. A close relationship was observed between improvement in symptoms by plasma exchange and a decrease in interleukin-8 level, suggesting that this chemokine may be related to the development of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome after bone marrow transplantation.

Adult↗

Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study.

In order to improve the disappointing prognosis of adult patients with acute lymphoblastic leukemia (ALL), we applied similar induction therapy as that used for acute myeloid leukemia (AML), ie frequent administration of doxorubicin (DOX). DOX 30 mg/m(2) was administered from days 1 to 3 and from days 8 to 10 together with vincristine, prednisolone, cyclophosphamide and L-asparaginase, followed by three courses of consolidation and four courses of intensification. From December 1993 to February 1997, 285 untreated adult patients with de novo ALL were entered. Of 263 evaluable patients (age 15 to 59; median 31), 205 (78%) obtained complete remission (CR). At a median follow-up period of 63 months, the predicted 6-year overall survival (OS) rate of all patients was 33%, and disease-free survival (DFS) rate of CR patients was 30%, respectively. By multivariate analysis, favorable prognostic factors for the achievement of CR were age <40 and WBC <50 000/microl; for longer OS were age <30 and WBC <30 000/microl; and for longer DFS of CR patients were FAB L1 and ALT <50 IU/l. Among 229 patients who had adequate cytogenetic data, 51 (22%) had Philadelphia (Ph) chromosome. Ph-negative chromosome was a common favorable prognostic factor for CR, longer OS and DFS. DFS was not different between early sequential intensification (n = 48) and intermittent intensification (n = 43) during the maintenance phase. Among CR patients under 40 years old, the 6-year survival was not different between the allocated related allo-BMT group (34 patients) and the allocated chemotherapy group (108 patients). However, among patients with Ph-positive ALL, the survival of patients who actually received allo-BMT was superior to that of patients who received chemotherapy (P = 0.046).

Antibiotics, Antineoplastic↗

Evidence that action potential generation is not the exclusive determinant to trigger spontaneous myogenic contraction of guinea-pig urinary bladder smooth muscle.

Urinary bladder smooth muscle (UBSM) exhibits spontaneous contraction. This spontaneous mechanical activity is myogenic and can be closely related to the UBSM cell action potential to facilitate Ca2+ influx through voltage-gated Ca2+ channels. In the present study, to know whether this membrane electrical event is the exclusive mechanism to trigger spontaneous smooth muscle contraction, we compared the inhibitory effects of Ca2+ channel blockers on the spontaneous action potential and mechanical activity in the isolated guinea-pig UBSM. Both action potential and rhythmic contraction were generated spontaneously in the presence of atropine (1 microM), phentolamine (1 microM), propranolol (1 microM), suramin (10 microM) and tetrodotoxin (1 microM), which suggest that both phenomena were myogenic in origin. Nisoldipine (100 nM) and diltiazem (10 microM) completely eliminated the generation of action potential whereas its frequency was dramatically increased by a dihydropyridine Ca2+ agonist, BayK 8644 (1 microM). In contrast to disappearance of action potential in the presence of Ca2+ channel blockers, spontaneous contraction of UBSM was inhibited only partly by nisoldipine or diltiazem and most of the mechanical components persisted in these channel blockers. These results indicate that spontaneous action potential in UBSM cell is generated through the activation of L-type voltage-gated Ca2+ channels. The subsequent elevation of intracellular Ca2+ concentrations during a burst of action potentials can be partly responsible for the induction of UBSM mechanical activity. In addition, the present study provides evidence that UBSM spontaneous mechanical activity is also attributable to the mechanism(s) other than the generation of Ca2+ spike.

Action Potentials↗

Clinical, histopathological and immunological distinction in two cases of IgA pemphigus.

Two cases of IgA pemphigus, one of the subcorneal pustular dermatosis (SPD) type and one of the intraepidermal neutrophilic IgA dermatosis (IEN) type, are described. IgA anti-keratinocyte cell surface antibodies reacted only with the uppermost epidermis in the SPD type but with the entire epidermis in the IEN type. A cDNA transfection test for desmocollins (Dsc) revealed that IgA antibodies of the SPD type reacted with Dsc1, but the IEN type did not react with any of the Dsc isoforms (Dsc1-3). ELISA for desmoglein 1 (Dsg1) and Dsg3 showed that neither of the cases had antibodies to Dsg - of either the IgG or IgA subtype. These results confirm that the autoantigen in SPD-type IgA pemphigus is Dsc1, whereas the antigen in most cases of IEN-type IgA pemphigus is unknown.

Aged↗

Enhancement of bile tolerance in lactococci by Tween 80.

AIMS: The aim of this study is to clarify the effect of Tween 80 on bile tolerance of lactococci. METHODS AND RESULTS: Four out of the six strains of lactococci could grow in broth containing 0.3% bile in the presence of 1% Tween 80, but grew slightly or not at all in the absence of Tween 80. Growing with Tween 80 altered the fatty acid composition of all three strains tested, but it is not clear which fatty acid influences bile tolerance. Material that absorbed light at 260 nm leaked from the cells tested with bile, but the leakage was decreased by addition of 1% Tween 80. Coincidentally, the decrease in the cell count by exposure to bile was suppressed by addition of Tween 80. CONCLUSIONS: Tween 80 enhances bile tolerance of some strains of lactococci. SIGNIFICANCE AND IMPACT OF THE STUDY: It is clarified that Tween 80 in the broth contributes to the bile tolerance of lactococci by reducing the cellular leakage caused by bile.

Bile↗

Influence of lactococcal plasmid on the specific growth rate of host cells.

AIMS: To investigate a lactococcal plasmid responsible for a reduction in growth rate of its host cell. METHODS AND RESULTS: Lactococcus lactis subsp. lactis biovar. diacetylactis DRC1 carries a high number of plasmids. The DRC1 wild-type strain was found to grow more slowly than a plasmid-free derivative of DRC1. The plasmids extracted from DRC1 together with an indicator plasmid were cotransformed into the plasmid-free strain DRC1021. A 7.4-kb cryptic plasmid, designated pDR1-1, was found to significantly affect the maximum specific growth rate ( micro max) of the host cell. Polymerase chain reaction (PCR) analysis was carried out in order to detect the presence of pDR1-1 in the other L. lactis strains. The micro max of the single pDR1-1-positive strain was determined to be the same as that of DRC1. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that pDR1-1 (or a pDR1-1-like plasmid) is a critical factor in the reduction of the micro max of DRC1, and that its effect on the micro max is significantly greater than that of any other coexisting plasmid.

Fermentation↗

Superior vena cava syndrome after bone marrow transplantation caused by aspergillosis: a case report.

Aspergillosis is known for the variety of unusual presentations in immuno-suppressed patients. We report a patient in whom aspergillosis caused the superior vena cava (SVC) syndrome. A 37-year-old woman became febrile soon after bone marrow transplantation (BMT). Chest radiography demonstrated a 5-cm mass extending from the right lung apex to the right supraclavicular fossa beside her Hickman catheter. She then developed SVC syndrome, which progressed despite treatment. Despite recovery of the white blood cell count, the patient continued to deteriorate, became comatose, suffered a cardiac arrest and died 31 days after BMT. Autopsy revealed Aspergillus infection at the apex of the right lung associated with innominate artery thrombosis.

Adult↗

Similarity between eruptions induced by sulfhydryl drugs and acute cutaneous graft-versus-host disease after bone marrow transplantation.

Cutaneous GVHD is histologically similar to eruptions induced by drugs containing a sulfhydryl group. The levels of interleukin-2 and interleukin-2 receptor were determined in a group of patients undergoing bone marrow transplantation (BMT) without graft-versus-host disease or any other complications and in a group with cutaneous graft-versus-host disease (GVHD) alone. In patients who only developed cutaneous GVHD, both interleukin-2 and inter-leukin-2 receptor levels were elevated when the disease was evident. As the elevation of these parameters became more marked, the grade of cutaneous graft versus-host disease also increased. In some patients, only one of the two parameters was elevated and the grade of graft-versus-host disease was low or no skin manifestations were seen. These findings suggest that interleukin-2 and interleukin-2 receptor act together in the development of cutaneous GVHD. This study also showed that the mechanism of cutaneous GVHD resembles that involved in the induction of eruptions by sulfhydryl-containing drugs.

Acute Disease↗

Changes in the populations of mitotic and apoptotic cells in white follicles during atresia in hens.

The aim of this study was to determine whether the population of mitotic cells changes in correlation with apoptotic cell population in follicular tissues during atresia of white follicles in hens. Hens were injected with 5-bromo-2'-deoxyuridine (BrdU) 1 h before tissue collection. The small white follicles were classified as healthy follicles and as early or late atretic follicles by histological observation. Mitotic and apoptotic cells were determined by immunocytochemistry for BrdU and terminal deoxytranceferase-mediated dUTP nick end labeling (TUNEL), respectively. The BrdU labeling was observed in some of the granulosa cells and thecal fibroblast-like cells in healthy follicles, whereas the population of the labeled cells was reduced in the granulosa and theca layers of atretic follicles. The image analysis confirmed that the frequency of BrdU-positive cells declined significantly in the granulosa and theca layers of early atretic follicles compared with those of healthy follicles. In contrast, the TUNEL-positive cells were negligible in healthy follicles. However, they were localized in the granulosa and theca layers of early and late atretic follicles, and those in the theca layer were more inside than outside. The frequency of TUNEL-positive cells was significantly increased with the progress of atretic changes. These results suggest that the population of mitotic cells decreases in association with increase of apoptotic cells during the atretic process of white follicles.

Animals↗

Effects of inducible nitric oxide synthase and xanthine oxidase inhibitors on SEB-induced interstitial pneumonia in mice.

The authors have previously reported that intratracheal instillation of staphylococcal enterotoxin-B (SEB) induced interstitial pneumonia (IP) in autoimmune-prone mice. SEB-reactive T-cells were critically involved in the development of IP in this model. Concern has arisen about the hazards of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the process of lung injury and fibrosis. Therefore, the involvement of nitric oxide (NO) and superoxide anion (O2-) in the pathogenesis of IP in this autoimmune-prone model has been investigated. Nitrite/nitrate levels were increased in bronchoalveolar lavage (BAL) fluid and serum from SEB-injected mice. The signal of the NO-(N-(dithiocarboxy) sarcosine)2-Fe2+ complex was detected in the SEB-injected lung and whole blood by electron paramagnetic resonance (EPR) spectroscopy. NO production was significantly decreased by aminoguanidine (AG) treatment. Xanthine oxidase (XO) activity in the lung, BAL fluid, and plasma was increased with instillation of SEB, and 4-amino-6-hydroxypyrazolo(3,4-d)-pyrimidine (AHPP) significantly inhibited XO activity. Moreover, both AG and AHPP significantly decreased production of pro-inflammatory cytokines, numbers of infiltrated cells in BAL fluid, and the area of thickened alveolar septa in the SEB-injected lung. In conclusion, the overproduction of nitric oxide and super oxide anion were implicated in the pathogenesis of interstitial pneumonia, and inducible nitric oxide synthase and xanthine oxidase inhibitors had protective effects against interstitial pneumonia in this model.

Animals↗

Cholesterol removal from media by lactococci.

Elevated serum cholesterol in humans is generally a risk factor correlated with the development of coronary heart disease. It has been reported that a culture of Lactobacillus acidophilus actively taking up cholesterol from a laboratory medium would function in vivo to exert a hypocholesterolemic effect. In the present study, seven strains of the genus Lactococcus were examined for their ability to remove cholesterol from laboratory media during growth. All strains of lactococci tested could remove cholesterol from media without degrading cholesterol. The amount of cholesterol removed was strain specific. Among them, Lc. Lactis subsp. lactis biovar diacetylactis N7 could remove as much cholesterol as L. acidophilus ATCC 43121, which had a beneficial influence on serum cholesterol levels in pigs. The manner of cholesterol removal by strain N7 corresponded to the manner of its growth. The growth of strain N7 (growth yield and growth efficiency) was enhanced. The fatty acid composition of the cells of strain N7 was altered by removing cholesterol from the media. The ability to remove cholesterol was also observed in the heat-killed cells of strain N7. However, the amount of cholesterol removed by the cells during growth was significantly higher than that removed by the heat-killed cells. Thus, strain N7 has the ability to remove cholesterol from media independently of whether cells are viable. These results indicate that administration of strain N7 in vivo may well be promising on the hypocholesterolemic effect.

Cholesterol↗

High prevalence of Epstein-Barr virus in gastric remnant carcinoma after Billroth-II reconstruction.

BACKGROUND: Epstein-Barr virus (EBV) has been detected in about 10% of gastric carcinoma cases worldwide, and a high prevalence of EBV involvement in gastric remnant carcinoma has been reported recently. Details of the background remnant stomach of EBV-positive lesions, however, have not been well clarified. METHODS: We screened 17 consecutive gastric remnant carcinoma lesions resected surgically. To detect EBV, we used in situ hybridization (ISH) for EBV-encoded small RNA1 (EBER-1) and we compared the clinicopathologic feature between EBV-positive and -negative gastric remnant carcinoma cases. RESULTS: EBV was detected in 41.8% (7 of 17) of the lesions by EBER-1 ISH. All 7 EBV-positive lesions developed in the anastomotic site had undergone Billroth-II reconstruction excess 20 years previously (mean 26.4 years). Histologically, all EBV-positive lesions were poorly differentiated adenocarcinomas with intense lymphocyte infiltration. In the adjacent mucosa of carcinomas, moderate or marked intestinal metaplasia was found in 85.7% (6 of 7) of EBV-positive lesions and in 40% (4 of 10) of EBV-negative lesions. CONCLUSIONS: EBV infection is strongly associated with gastric remnant carcinoma. Atrophic change of remnant gastritis in Billroth-II anastomoses is considered to be the carcinogenic background for EBV-positive gastric remnant carcinoma.

Adenocarcinoma↗

Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction.

Reducing sugars can react nonenzymatically with the amino groups of proteins to form Amadori products and subsequently cross-linked, heterogeneous fluorescent derivatives called advanced glycation end products (AGE). AGE can arise in vivo from various types of reducing sugars or dicarbonyl compounds and their formation and accumulation are known to progress during normal aging. In individuals with diabetes mellitus, this progression is greatly accelerated. The aim of the present study was to investigate which kinds of serum AGE components were associated with the severity of diabetic retinopathy in 72 type 2 diabetic patients without renal dysfunction. Serum levels of glucose-, glyceraldehyde- or methylglyoxal-derived AGE (methyl-AGE) were measured by an enzyme-linked immunosorbent assay. No significant correlations were found between serum levels of various AGE and HbA1c level, current age, systolic and diastolic pressure, diabetes duration, serum creatinine or blood urea nitrogen level in type 2 diabetic patients. A significant elevation of serum glucose-AGE was found to be associated with severity of diabetic retinopathy. While no differences in serum methyl-AGE levels were found between patients with diabetic retinopathy and those without, serum levels of glyceraldehyde-AGE showed a tendency to increase as normal retinal status advanced to simple and proliferative retinopathy (p = 0.06). The present results suggest that among various types of AGE, glucose-AGE serum levels may be a useful marker of diabetic retinopathy in type 2 diabetic patients without renal dysfunction.

Diabetes Mellitus, Type 2↗