Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 109 records · Page 6Linked to original sources

PubMed2001

Percutaneous extracorporeal life support for treatment of fatal mechanical complications associated with acute myocardial infarction.

Mechanical complications of acute myocardial infarction (AMI), such as free wall rupture, ventricular septal perforation (VSP), and mitral regurgitation due to papillary muscle rupture, are associated with high mortality rates. These complications result in extreme deterioration and increased risk of death in patients who do not receive timely resuscitation and surgical treatment. We studied the effectiveness of percutaneous extracorporeal life support (ECLS) for fatal mechanical AMI complications. Nine patients (7 men and 2 women, mean age 69 +/- 6 years) who suffered circulatory collapse refractory to conventional resuscitation were treated with ECLS. Circulatory collapse was caused by free wall rupture in 4 patients, VSP in 4, and mitral regurgitation due to papillary muscle rupture in 1. All patients were successfully resuscitated by ECLS and underwent surgical repair with conventional cardiopulmonary bypass. Eight patients required ECLS after surgery. Four of the 9 patients (2 with free wall rupture, 1 with VSP, and 1 with papillary muscle rupture) were successfully weaned from ECLS and were discharged. Three of the 4 survivors had no major complications, but the remaining survivor suffered neurological deficit. Four patients died while on devices. The duration of ECLS was from 13 to 167 h (mean 76 +/- 57 h) with a maximum bypass flow of 2.0 to 3.9 L/min (mean 2.9 +/- 0.6 L/min). There were no device-related complications during the support period. Total weaning rate was 56% (5/9), and survival was 44% (4/9). We conclude that ECLS can provide appropriate circulatory support during resuscitation and subsequent postoperative circulatory support for cardiovascular collapse associated with AMI complications.

Aged↗

PubMed2001

Chondrocyte-derived ezrin-like domain containing protein (CDEP), a rho guanine nucleotide exchange factor, is inducible in chondrocytes by parathyroid hormone and cyclic AMP and has transforming activity in NIH3T3 cells.

OBJECTIVE: The purpose of this study is to investigate stage- and hormone-dependent expression of chondrocyte-derived ezrin-like domain containing protein (CDEP), a putative guanine nucleotide exchange factor (GEF) for Rho in chondrocytes, and demonstrate the guanine nucleotide exchange activity of this protein in vitro, as well as the transforming activity in NIH3T3 cells. METHODS: The expression of CDEP mRNA in growth plate chondrocytes in vivo and in vitro was examined by RT-PCR Southern analysis. The guanine nucleotide exchange activity was determined using a recombinant CDEP peptide containing the DH and PH domains in Sf9 cell lysates. The transforming activity was examined using NIH3T3 cells transiently transfected with a truncated CDEP cDNA. RESULTS: CDEP mRNA was expressed at the highest level in the hypertrophic (terminal) stage of chondrocytes in vivoand in vitro. Parathyroid hormone (PTH) elicited a biphasic increase of CDEP mRNA in chondrocytes. The CDEP mRNA level increased within 1 h, then decreased nearly to the control level at 3 h. Thereafter the mRNA level started to increase at 6 h, reaching a plateau at 24 h. Dibutyryl cyclic AMP had a similar effect on CDEP expression in chondrocytes. The dissociation of [3H]GDP from RhoA was stimulated dose-dependently by Sf9 cell lysates containing the CDEP peptide. Furthermore, transfection of a truncated CDEP cDNA induced focus formation in NIH3T3 cultures. CONCLUSIONS: CDEP is a novel GEF for Rho family GTPases with the transforming activity. CDEP may play a role in mediating or modulating the action of cAMP-elevating hormones on maturing chondrocytes.

Animals↗

PubMed2001

Suppression of apoptosis is responsible for increased thickness of intestinal mucosa in streptozotocin-induced diabetic rats.

Intestinal mucosal growth is a common, but uncharacterized, observation associated with diabetes mellitus. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. To determine the contribution of apoptosis to the overall maintenance of intestinal growth, we examined intestinal apoptosis in the well-characterized streptozotocin (STZ)-induced diabetes rat model. Rats were injected with STZ (75 mg/kg body weight), thereafter they were allowed free feeding or restricted feeding for 3 weeks. Food intake and intestinal mucosal height were evaluated. In a second experiment, additional groups of animals were injected with STZ and were fed ad libitum for 1 or 3 weeks. Ornithine decarboxylase (ODC) activity, ratio of fragmented DNA to total DNA, electrophoresis of fragmented DNA, and Western blot analysis of caspase-3 were examined. Food intake gradually increased in free-feeding rats after induction of diabetes. Intestinal mucosal height in free-feeding diabetic rats was approximately 25% longer than controls, but this increase in mucosal height was not observed in restricted-fed diabetic rats (25 g/d). ODC activity in intestinal mucosa in diabetic rats did not differ from that of control rats. Percent fragmented DNA of diabetic rats 1 week after STZ injection was significantly lower than that of control rats, and this decrease returned to the control level 3 weeks after STZ treatment. Active form of caspase-3 was attenuated 1 week after drug treatment. Attenuated effect of diabetic rats on intestinal apoptosis did not affect increased apoptosis after ischemia-reperfusion. Suppression of apoptosis in the early days of STZ-induced diabetes was responsible for the increased mucosal height in the small intestine in STZ-induced diabetic animals.

Animals↗

PubMed2001

Induction of basic helix-loop-helix protein DEC1 (BHLHB2)/Stra13/Sharp2 in response to the cyclic adenosine monophosphate pathway.

DEC1 (BHLHB2)/Stra13/Sharp2, a basic helix-loop-helix (bHLH) transcription factor has been suggested to be involved in the control of proliferation and/or differentiation of several cells including nerve cells, fibroblasts and chondrocytes. In the present study, we examined the effect of parathyroid hormone (PTH), dibutyryl cAMP (Bt2cAMP) and forskolin on the expression of DEC1 in various cells. In rabbit chondrocyte cultures, PTH or Bt2cAMP increased the DEC1 mRNA level within 1 h. Thereafter, the DEC1 mRNA level rapidly decreased to the basal level at 3 h, and increased at 6-24 h. In cultures of a mouse embryo prechondrogenic cell line ATDC5, PTH or forskolin, an activator of adenylate cyclase, also increased the DEC1 mRNA level within 1 h. Furthermore, in all evaluated cell lines of human fibroblasts, canine epithelial cells, human carcinoma, human glioblastoma and human melanoma, Bt2cAMP increased the DEC1 mRNA level within 1-3 h. Studies with actinomycin D and cycloheximide indicated that the enhancement of DEC1 mRNA by cAMP was not due to mRNA stabilization and did not require new protein synthesis. These findings suggest that DEC1 is a novel direct target for cAMP in wide types of cells, and that the bHLH protein is involved in the control of gene expression in cAMP-activated cells.

Animals↗

PubMed2001

Programmed cell death in rat intestine: effect of feeding and fasting.

BACKGROUND: The regulation of intestinal cell death by luminal factors is poorly understood. The objectives of this study were to determine whether a diurnal rhythm of intestinal apoptosis exists, and to determine the role that feeding and fasting play in this process. METHODS: Mucosal apoptotic death was measured in fed and 24-h fasted rats and at various times after feeding by DNA fragmentation and in situ immunohistochemical staining (TUNEL). RESULTS: In 24-h fasted rats, 32% of total mucosal DNA was fragmented as compared to 9% in fed animals. In both jejunal and ileal segments, the fragmented DNA exhibited characteristic apoptotic DNA ladders on agarose gels. Immunohistochemical staining revealed significant location of apoptotic cells at the upper third of the intestinal villus. In the duodenum, DNA fragmentation at 6-12 h post feeding was 20% and decreased to 4% at 24 h. In comparison, DNA fragmentation in the jejunum and ileum was low from 0 to 6 h post feeding (2%-9%) and significantly increased at 12 h (18% versus 12%) and 24 h (30% versus 32%), respectively. These results are consistent with a temporal relationship between percent fragmented DNA and time after feeding with greater cell death at longer fasting period. A postprandial rhythm of DNA fragmentation was evident in the jejunum and ileum, in which fragmentation was at a peak between 0900 h and 1200 h. CONCLUSION: Collectively, the data show that initiation of apoptosis in apical enterocytes is coincident with cessation of feeding and commencement of fasting, and is consistent with a rhythm of programmed cell death in these cells that parallels the cyclical pattern of feeding and fasting.

Animals↗

PubMed2001

Pathological features of the lung in fatal high altitude pulmonary edema occurring at moderate altitude in Japan.

In order to characterize the pathological features of high altitude pulmonary edema (HAPE) occurring at moderate altitude in Japan, we performed routine hematoxylin and eosin (HE) staining in lung materials from HAPE autopsied cases. We also undertook advanced immunohistochemical staining for observation of type II pneumocytes, pulmonary surfactant (PS), and mast cells in the lung of HAPE cases to examine the biological changes within the lung parenchyma. The pathological findings of HAPE were characterized by alveolar edema, congestion of pulmonary vessels, alveolar hyaline membranes, alveolar hemorrhage, and multithrombi and fibrin clots, but maintained alveolar structure. The immunostaining results showed that the type II pneumocytes were cellular fusion, deformity, and exfoliation from the walls of alveoli; the PS not only lined the alveolar surface, but was also patchily distributed within alveoli; and the number of mast cells were increased (9.0 +/- 0.9 cells/mm(2)) compared to that in controls (1.1 +/- 0.4 cells/mm(2)) (p < 0.01). We conclude that the pathological features of HAPE at moderate altitude in Japan are similar to others reported worldwide, and that the type II pneumocytes, PS, and mast cells may contribute to some extent to pathophysiological parts in the development and progression of HAPE.

Adolescent↗

PubMed2001

Primary synovial sarcoma of the lung: a case report confirmed by molecular detection of SYT-SSX fusion gene transcripts.

We report a rare case of primary synovial sarcoma of the lung. The patient was a 49-year-old woman who presented with a well-defined oval-shaped mass in the left upper lobe on a chest radiograph. A malignant pulmonary tumor was suspected and consequently a left upper lobectomy was performed. Grossly, the tumor measured 5 x 4 cm, was whitish-yellow in color and soft in consistency. Histologically, the tumor showed a dense proliferation of short spindle cells, partly arranged in interlacing fascicles. In some areas a hemangiopericytoma-like pattern, stromal myxoid change and necrosis of various sizes were noted. Numerous mitotic figures were also seen. Immunohistochemically, the tumor cells were positive for epithelial markers such as cytokeratin and epithelial membrane antigen. As these features suggested a monophasic fibrous type of synovial sarcoma, we examined for the presence of SYT-SSXfusion gene transcripts using RNA samples from the frozen tumor tissue. A reverse transcription polymerase chain reaction amplified a single 583-base pair fragment characteristic of synovial sarcoma. As no other tumorous lesions were found during a follow-up period of 1 year, primary synovial sarcoma of the lung was our final diagnosis. This tumor should be considered in the differential diagnosis of round to short spindle cell tumors arising in the lung.

Female↗

PubMed2001

Treated natural history of superficial bladder cancer.

BACKGROUND: The present study was conducted to examine the natural history of superficial bladder cancer. METHODS: One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed. RESULTS: The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt. CONCLUSIONS: These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group.

Aged↗

PubMed2001

Template directed DNA photoligation via substituted 2'-deoxyuridine.

An efficient and reversible template-directed photoligation of oligodeoxynucleotides (ODNs) using 5-carboxyvinyldeoxyuridine (CVU) was described. We have also demonstrated about photochemical synthesis of circularized DNA and padlocking plasmid DNA via CVU mediated photoreaction.

Base Sequence↗

PubMed2001

Induction of mild intracellular redox imbalance inhibits proliferation of CaCo-2 cells.

Intracellular redox status plays a critical role in cell function, such as proliferation. Oxidative stress, which elicits redox imbalance, also affects cell growth. Therefore, it is often difficult to distinguish the effects of redox imbalance from those of oxidative stress. The objective of this study was to determine the role of redox imbalance independent of reactive oxygen species (ROS) production, in proliferation of human colonic CaCo-2 cells. Low concentrations of diamide plus 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) increased intracellular GSSG and decreased GSH and the GSH:GSSG ratio. These changes occurred within 30 min, which preceded a decrease in thymidine incorporation at 6 and 24 h. ROS formation was not detected under these conditions. This suppression of cell proliferative activity was attenuated by N-acetyl cysteine, in parallel with restoration of the intracellular GSH redox status. dl-buthionine-[S, R]-sulfoximine (BSO) decreased intracellular GSH level, but did not change the GSH:GSSG ratio. BSO alone had no effect on cell proliferation, but its presence exaggerated the suppressive effect of diamide plus BCNU. Flow cytometric analysis showed that cells were arrested at G1-to-S transition and G2/M phase. Collectively, this study shows that mild intracellular redox imbalance inhibited cell proliferation independent of ROS generation. Moreover, cells with compromised cellular GSH were susceptible to redox imbalance-induced inhibition of proliferation.

Acetylcysteine↗

PubMed2001

Appropriate dosing of pilsicainide hydrochloride in patients on hemodialysis.

Appropriate dosing of pilsicainide hydrochloride, an anti-arrhythmic drug excreted via the kidney, was investigated in patients on dialysis. Ten chronic hemodialysis patients with coexisting severe palpitation of supraventricular premature contractions (SVPC) were treated with 25 mg of pilsicainide hydrochloride before dialysis. All of their plasma concentrations were maintained within the therapeutic range and their mean dialysis rate was 32%. After 2 weeks, 7 patients were followed with consecutive daily dose treatment. In 3 of them, the dosage was returned to the single pre-dialysis administration because of the elevated plasma concentration reaching the toxic range 1 month after the start of administration. The dose schedule was maintained, and plasma pilsicainide concentrations remained within the therapeutic range during the 6-month follow-up. No abnormal findings were found in any parameters of electrocardiography, echocardiography or biochemistry. The number of SVPC diminished > 90% compared to the pretreatment level.

Anti-Arrhythmia Agents↗

PubMed2001

Effect of the central nervous system on mucosal growth and apoptosis in the small intestine.

Recently our studies have demonstrated that the central nervous system regulates in part mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase (ODC) activity is a key enzyme for polyamine synthesis which plays an important role for the intestinal mucosal growth. We have demonstrated that the increase of ODC activity in the duodenum just before the dark period is abolished by truncal vagotomy and that the infusion of 2-deoxy-D-glucose into the third cerebroventricle activates ODC activity in the small intestine. Epithelial homeostasis is balanced by regulation of cell proliferation and cell death. Our preliminary data showed that intestinal mucosal apoptosis decreased in the ventromedial-hypothalamus-lesioned rat. These results indicate that the central nervous system, in addition to local factors, is related to regulation of mucosal homeostasis in the intestinal mucosa.

Animals↗

PubMed2001

Interferon-gamma stimulates fractalkine expression in human bronchial epithelial cells and regulates mononuclear cell adherence.

Bronchial epithelial cells may contribute to airway inflammation by releasing chemokines and expressing surface membrane molecules involved in the adhesion of leukocytes. We found that interferon (IFN)-gamma stimulates expression of fractalkine, a potent chemoattractant for monocytes and T lymphocytes, in a time- and concentration-dependent manner by normal human bronchial epithelial cells in culture. Enhanced expression of fractalkine messenger RNA was confirmed by both reverse transcription/polymerase chain reaction and Northern blotting. IFN-gamma also stimulated fractalkine protein production and most of the protein was found in cell lysates. The adherence of blood mononuclear cells to the monolayers of bronchial epithelial cells stimulated with IFN-gamma was partly inhibited by an antifractalkine antibody. An antibody against intercellular adhesion molecule-1 was similarly effective in inhibiting the adhesion. Fractalkine protein levels in bronchoalveolar lavage fluids from patients with inflammatory diseases correlated positively with mononuclear cell counts in the fluids. The bronchial epithelium in a biopsy specimen of lung cancer was stained positively by immunofluorescent staining for fractalkine. We conclude that IFN-gamma stimulates fractalkine expression by bronchial epithelial cells, which may play an important role in inflammatory responses by recruiting mononuclear leukocytes to the bronchial epithelium.

Base Sequence↗

PubMed2001

Dose estimation based on a behavior survey of residents around the JCO facility.

The NIRS staff interviewed the residents in the evacuated zone around the JCO facility in Tokai-mura on 19 and 20 November, 1999, to obtain the following parameters every 30 minutes starting from 10:35 A.M. on 30 September to 6:15 A.M. on 1 October: the distance from the precipitation tank, the type of the house, positions in the house, wall materials and their thickness in order to estimate individual doses due to the accident. The ambient dose equivalents were obtained based on monitoring data during the accident. In addition, computer calculations were conducted to evaluate the conversion factor from ambient dose equivalent to effective dose equivalent as well as the shielding effect of the house or factory to estimate the effective dose equivalent to the residents. The estimated individual doses based on the behavior survey were in the range from zero to 21 mSv. The individual doses were reported to the residents during the second visit to each house and factory at the end of January, 2000.

Behavior↗

PubMed2001

An interlaboratory study of a candidate reference method for platelet counting.

A multinational interlaboratory task force explored the important variables of platelet reference counting and developed a candidate flow cytometric reference method based on the RBC/platelet ratio. A multicenter comparison was performed to determine whether the method met the necessary criteria and was precise enough to be recommended as a new reference method. Each laboratory analyzed serial dilutions of normal specimens, stabilized material, and at least 60 patient specimens with a range of platelet counts from 1 to 400 x 10(3)/microL (1-400 x 10(9)/L). Pooled analysis of the serial dilutions showed that RBC-platelet and RBC-RBC coincidence events became negligible at sufficiently high dilutions (i.e., > 1:1,000). All laboratories demonstrated excellent intra-assay and acceptable interlaboratory precision. Two antibodies (CD61 and CD41) were used for identifying platelets and individually gave acceptable results, but in a minority of samples, staining differences were observed. The optimum method thus uses a double-labeling procedure with a final dilution factor of 1:1,000. The study demonstrated that this method meets the criteria for a reference platelet count.

Anticoagulants↗

PubMed2001

Hypersensitivity pneumonitis induced by spores of Lyophyllum aggregatum.

OBJECTIVES: Lyophyllum aggregatum (LA) is called Shimeji in Japanese and is eaten commonly as a mushroom. Shimeji mushrooms are cultivated in an indoor environment all year round. This study aimed to clarify the clinical features of hypersensitivity pneumonitis (HP) induced by LA. PATIENTS AND SETTING: Ten patients showed mild respiratory symptoms including dry cough, sputum, and low-grade fever. We tried to characterize the clinical features and the findings using chest high-resolution CT (HRCT), pulmonary function tests (PFTs), and BAL fluid (BALF) tests in patients with HP induced by LA. HP was diagnosed from clinical features, HRCT findings, BALF findings, lung histology, and lymphocyte stimulation tests (LSTs) for LA. RESULTS: Laboratory findings showed mean (+/- SD) elevated levels of C-reactive protein (0.78 +/- 1.3 mg/dL), erythrocyte sedimentation rate (48 +/- 23 mm/h), and gamma-globulin (26.9 +/- 7.6%). PFTs revealed a slight decrease in the percentage diffusing capacity of the lung for carbon monoxide, possibly due to the presence of epithelial granulomas in the alveoli. Although 4 of 10 patients showed normal findings on the chest radiograph (CXR), chest HRCT findings of all patients showed centrilobular small nodules and diffuse ground-glass opacities. The BALF testing revealed an increase in total cell counts, showing predominantly activated T lymphocytes. The CD4/CD8 cell ratio was significantly decreased (0.5 +/- 0.3). The results of the LSTs were positive in seven of seven cases. CONCLUSIONS: Since patients with HP induced by LA typically have mild respiratory symptoms and sometimes normal CXR findings, their conditions might remain undiagnosed. However, the chest HRCT images showed the typical subacute phase of HP.

Adult↗

PubMed2001

Detection of B virus infection in cynomolgus monkeys by ELISA using simian agent 8 as alternative antigen.

The use of simian agent 8 (SA8) as an antigen for B virus (BV) antibody detection was evaluated in cynomolgus monkeys. Seventy-two sera judged as positive using BV antigen were all positive when the SA8 antigen was used. Out of 28 BV-negative sera 2 were positive against the SA8 antigen and one serum was classified as indeterminate. The present data indicates that detection of BV antibody can be achieved accurately and safely by enzyme-linked immunosorbent assay (ELISA) using SA8 antigen.

Animals↗

PubMed2001

Possible role of peripheral CD14low monocytes in the development of collagen-induced arthritis in cynomolgus monkeys (Macaca fascicularis).

The changes in levels of peripheral major lymphocyte subsets were monitored with 10 adult cynomolgus monkeys (5 females and 5 males) during the 9 weeks after immunization with chick type-II collagen in Freund's complete adjuvant. Three females and 3 males developed overt arthritis determined by swelling of small joints and increase of plasma alkaline phosphatase as well as C-reactive protein. An increase of CD16+ NK cells was observed in four non-arthritis-developed monkeys (two females and two males). There was no significant difference in the fluctuation pattern of CD4+ T cell, CD8+ T cell and CD20+ B cell levels between arthritis-developed monkeys and non-developed ones. In addition, the percentages of CD45RA+ CD4+ T cells to total CD4+ T cells, CD28- CD8+ T cells to total CD8+ T cells, and IgD- B cells to total B cells did not significantly differ between them. On the other hand, a significant increase was demonstrated in CD14-positive cells at 3 weeks after immunization in only arthritis-developed monkeys regardless of sex. The expression of CD14 antigen on the surface of increased cells was low in comparison with those appearing in blood obtained before immunization. In addition, increased CD14low cells showed no response to LPS stimulation. However, there was no significant difference in antibody titer to both chick type-II and monkey type-II collagen between arthritis-developed monkeys and non-developed ones. These results suggest that an increase in number of CD14low monocytes with immature function might be a part of the autoimmune response, and that the appearance of these cells is of pathogenic importance in the arthritic process in cynomolgus monkeys regardless of the production of autoantibody.

Alkaline Phosphatase↗