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Biomedical subjects

Yuji Hiramatsu

Publications and source records attributed to Yuji Hiramatsu.

At least 37 records · Page 2Linked to original sources

Intracardiac lead fracture in an implantable cardioverter-defibrillator.

A patient with an implantable cardioverter-defibrillator (ICD) experienced inappropriate shocks. X-rays revealed that the ventricular lead was fractured at a point, which seemed to be in a mechanical stress-free space in the heart. Multiple leads were entwined making a short flexible section sandwiched between the entwined area and the stiff coil susceptible to the stress from heart beats. The present case shows that indirect concentrated stress caused by restriction of lead flexibility can result in lead fracture. Upon implanting multiple endocardial leads, attention should be given to the relative position of each lead.

Adult↗

Term delivery choriocarcinoma patient with brain and lung metastases successfully treated by etoposide, methotrexate, actomycin D, cyclophosphamide and vincristine (EMA-CO) chemotherapy.

It is well known that antecedent term delivery and metastasis to sites other than the lungs and vagina are high risk factors for patients with gestational trophoblastic neoplasia. Here we report on a patient with choriocarcinoma who presented with brain and lung metastases after term delivery and was treated by EMA-CO chemotherapy. A 31-year-old woman delivered a healthy infant at term. Frequent episodes of hemoptysis occurred beginning 3 weeks after the delivery. On admission to our hospital, she had lesions in the uterus, lungs and brain as well as motor aphasia and hemiplagia. The pretreatment beta-hCG level was 21,000 ng/ml and the WHO score was 16 (high-risk group). The EMA-CO regimen was administrated as first-line chemotherapy and the patient achieved complete remission after 7 courses. Treatment was terminated after 11 courses and maintained with etoposide (25 mg/day) for 6 months. The patient has remained in complete remission for more than 16 years without other adjuvant therapies. We believe that EMA-CO can currently be considered the regimen of first choice for most high-risk patients with gestational trophoblastic neoplasia in view of its effectiveness and excellent tolerability.

Adult↗

[Surgical technique of leaflet extension in aortic valve regurgitation].

Detailed procedure of the leaflet extension technique in aortic valve regurgitation is described. The concept of the technique is to create a wide and deep coaptation zone by extending the prolapsed leaflets using glutaraldehyde-preserved autologous pericardium, and by suspending the commissures. The leaflet extension technique is a procedure of choice for aortic valve regurgitation in young patients who need to avoid strict anticoagulation therapy. A careful long-term follow-up is necessary to evaluate the durability of glutaraldehyde-preserved pericardium in aortic position.

Aortic Valve↗

Loss of basement membrane heparan sulfate expression is associated with pelvic lymph node metastasis in invasive cervical cancer.

Perlecan is a major heparan sulfate proteoglycan of basement membrane (BM) and binds to various cytokines and growth factors via its heparan sulfate glycosaminoglycan (HS-GAG) chains. The aim of this study was to investigate BM HS-GAG expression in invasive cervical cancers. We investigated the expression of BM HS-GAG by immunohistochemistry in 143 invasive cervical cancers and 30 metastatic lymph node samples, and analyzed correlations with various clinicopathological features. Furthermore, the gene expression levels of heparanase were assessed by RT-PCR in 52 invasive cervical cancer samples. HS-GAG expression index was significantly lower in cases of lymph node metastasis (p=0.01). There was no association between HS-GAG expression status and patient outcome. HS-GAG expression index in metastatic pelvic lymph nodes was significantly higher than that in the primary site (p=0.019). Furthermore, HS-GAG expression index was significantly lower in cases where heparanase mRNA expression was detectable (p=0.033). Heparanase mRNA expression is associated with the loss of BM HS-GAG expression, which is closely related to lymph node metastasis in invasive cervical cancers.

Adenocarcinoma↗

SSX expression in gynecological cancers and antibody response in patients.

The SSX genes are members of the cancer-testis (CT) antigen family. SSX2, the prototype SSX gene, was found by serological analysis of antigens by recombinant expression cloning (SEREX). Since little is known about SSX expression in gynecological malignancies, we investigated SSX mRNA expression in 115 gynecological cancer specimens and 25 normal control samples by RT-PCR. We also tested the humoral immune response to SSX2 and SSX4 using recombinant proteins. We found relatively high SSX4 mRNA expression in endometrial cancer (24%), ovarian cancer (13%), and cervical cancer (20%). In contrast, SSX1 and SSX2 mRNA expression was detected in not more than 4% of the gynecological cancer specimens analysed. No SSX mRNA expression was found in 25 normal specimens. Two gynecological cancer patients had antibodies against SSX4, whereas no antibody reactivity to SSX4 was found in the sera of 40 normal individuals. This suggests that SSX4 is a potential target for cancer vaccines in gynecological cancer patients.

Antibodies, Neoplasm↗

Use of artificial dermis and recombinant basic fibroblast growth factor for creating a neovagina in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome.

Vaginal agenesis is an uncommon, but not rare, condition. Although there are many methods for creating a neovagina, the optimal treatment is unknown. An 18-year-old woman with Mayer-Rokitansky-Küster-Hauser syndrome received vaginoplasty with a modified Wharton procedure using an artificial dermis (atelocollagen sponge). From 10 days after the operation, the patient was administered human recombinant basic fibroblast growth factor (bFGF) spray to accelerate epithelialization on the neovagina. At 50 days after the operation, we confirmed histological squamous epithelialization of the vaginal epithelium. At 12 months after the operation, the neovagina was at least 3.5 cm in width and approximately 8 cm in length. In this case, use of artificial dermis and recombinant bFGF to create a neovagina was an easy, less invasive and useful method.

Abnormalities, Multiple↗

High-frequency QRS potentials as a marker of myocardial dysfunction after cardiac surgery.

BACKGROUND: High-frequency QRS potentials are sensitive to myocardial ischemia. The aim of this study was to evaluate the usefulness of high-frequency QRS potentials as a marker of myocardial dysfunction after cardiac surgery. METHODS: Seventy patients undergoing coronary artery bypass grafting or heart valve surgery were involved. High-frequency QRS potentials were measured by signal-averaged electrocardiogram, and calculated as the root-mean-square voltage of the total QRS duration (RMST). The postoperative RMST was expressed as a percentage of the preoperative RMST. The mean RMST at 1 to 2 hours after removing the aortic cross-clamp was compared with the cardiac index, inotropic agents, and aortic cross-clamping time. The occurrence of ventricular tachycardia within 24 hours and the RMST at 2 postoperative days were also evaluated. Patients were divided into quartile groups from highest to lowest at postoperative RMST (groups 1, 2, 3, and 4, respectively, from maximum to minimum). RESULTS: In postoperative states, cardiac index significantly decreased in accordance with the RMST decrease in a stepwise manner, although there were no differences in cardiac index among the four groups preoperatively. Inotropic agents and aortic cross-clamping time increased as RMST decreased. A high rate of ventricular tachycardia within 24 hours and delayed RMST recovery at 2 postoperative days were seen in group 4. The curve of sensitivity and specificity showed that severe reduction (threshold, 35%) of RMST indicated low-output syndrome. CONCLUSIONS: The severe reduction of filtered high-frequency QRS potentials was related to myocardial dysfunction. Measurement of filtered high-frequency QRS potentials could become a useful, noninvasive, real-time monitor of myocardial dysfunction after surgery.

Cardiac Output, Low↗

Effects of nafamostat mesilate and minimal-dose aprotinin on blood-foreign surface interactions in cardiopulmonary bypass.

BACKGROUND: The pharmacological inhibition of blood-foreign surface interactions is an attractive strategy for reducing the morbidity associated with cardiopulmonary bypass. We compared the inhibitory effects of nafamostat mesilate (a broad-spectrum synthetic protease inhibitor) and minimal-dose aprotinin on blood-surface interactions in clinical cardiopulmonary bypass. METHODS: Eighteen patients undergoing coronary surgery were divided into three groups: (1) the control group (heparin, 4 mg/kg; n = 6), (2) the nafamostat mesilate group (heparin plus nafamostat, 0.2 mg/kg bolus followed by 2.0 mg/kg/h during cardiopulmonary bypass; n = 6), and (3) the aprotinin group (heparin plus aprotinin, 2.0 x 10(4) KIU/kg; n = 6). Platelet count, platelet aggregation, beta-thromboglobulin, prothrombin fragment F1.2, thrombin-antithrombin complex, plasminogen activator inhibitor-1, alpha2-plasmin inhibitor-plasmin complex, D-dimer, neutrophil elastase, and interleukin-6 were measured before, during, and after bypass. Bleeding times and blood loss were recorded. RESULTS: There were no significant differences between groups in platelet count, beta-thromboglobulin, plasminogen activator inhibitor-1, interleukin-6, bleeding times, or blood loss. Platelet aggregation was better preserved at 12 hours after surgery in the nafamostat and aprotinin groups than in the control group. Prothrombin fragment F1.2, thrombin-antithrombin complex and neutrophil elastase levels were significantly reduced by aprotinin, but not by nafamostat as compared with the control group. The alpha2-plasmin inhibitor-plasmin complex and D-dimer were significantly lower with either of the drugs. Aprotinin showed better control of D-dimer than did nafamostat. CONCLUSIONS: Nafamostat mesilate fails to reduce thrombin formation and neutrophil elastase release, whereas minimal-dose aprotinin inhibits both. Neither nafamostat nor aprotinin inhibits platelet activation. Nafamostat reduces fibrinolysis during cardiopulmonary bypass, although its effect is not as potent as aprotinin.

Aged↗

Eradication of HPV post-surgical treatments, its correlation with specific types, types of surgery and the physical status.

Low-risk human papillomaviruses (HPVs) will be completely eradicated as long as most visible lesions are treated. However, it is uncertain whether this is also the case for high-risk HPVs that are capable of causing cervical cancer. Many recent studies have demonstrated a high incidence of HPV persistence during post-conization or loop electrosurgical excision (LEEP) due to high-grade cervical intraepithelial neoplasia (CIN). In this report, we correlated the post-operative HPV status with pre-operative HPV type, types of surgery and HPV's physical status. Post-operative HPV E6 amplification by nested PCR was carried out for 157 female patients with positive pre-operative HPV. They underwent LEEPs, therapeutic laser conizations, and simple or radical hysterectomies. We found that high-risk types of HPVs were eradicated in 26.4% (42/159) of patients after extirpation of the lesions. The clearance rate of HPVs increased to 39.2% (40/102), excluding patients with other high-risk (OHR) kinds of type 31, 52b and 58, since OHR persisted after almost all surgeries. Eradication of HPV after radical hysterectomies are highly expected for patients with invasive cancer (70.0%, when excluding OHR), while more than half of them with CIN continue to carry pre-operative types of HPV or some different types from before treatment. Type 33 is most frequently persistent among types 16, 18 and 33. Persistent high-risk HPVs increase the risk for recurrence of post-surgical treatments of CIN, but the incidence is not high as long as the lesion is completely removed.

Carcinoma in Situ↗

Involvement of suppressor for Gal 1 in the ubiquitin/proteasome-mediated degradation of estrogen receptors.

The proteasome-mediated pathway involves the degradation of several nuclear receptors. Previously we demonstrated that the interaction between the suppressor for Gal 1 (SUG1) and nuclear receptors, the vitamin D receptor, or the pregnane X receptor was involved in proteasome-mediated degradation. In our recent experiments, we examined the potential role of SUG1 in the proteasome-mediated degradation of estrogen receptors (ER)alpha and -beta. Both ERs interacted with SUG1 in a ligand-dependent manner. Functionally, the overexpression of SUG1 inhibited both ERalpha- and ERbeta-mediated transcription in the presence of ligands. Transient expression studies demonstrated that the overexpression of wild-type SUG1 generated proteolytic fragments of both ERs and that these products were blocked by a proteasome inhibitor. The overexpression of SUG1 also enhanced the formation of ubiquitinated proteins of both ERs in the presence of ligand. On the other hand, bisphenol A (BSA), which activated ER-mediated transcription, did not enhance the interaction between ERbeta and SUG1. Furthermore, the degradation of ERbeta was much slower in the presence of BSA than in the presence of estradiol or phthalate, which is another endocrine-disrupting chemical. Also, BSA had no effect on the formation of proteolytic fragments of ERbeta, and neither did it have any effect on the ubiquitination of ERbeta. These findings indicate that the ubiquitin/proteasome-mediated degradation of both ER proteins may involve the interaction of SUG1 with both ERs. Moreover, BSA strongly blocked the ubiquitination and degradation of ERbeta compared with estradiol, suggesting that BSA may affect the ERbeta-mediated transcription of target genes by inhibiting ERbeta degradation.

ATPases Associated with Diverse Cellular Activitie↗

Antitumor effects of a soluble insulin-like growth factor I receptor in human ovarian cancer cells: advantage of recombinant protein administration in vivo.

Antitumor effects of a soluble form dominant negative of the type I insulin-like growth factor receptor (IGF-IR) designated as 486/STOP were evaluated in CaOV-3 human ovarian cancer cells by establishing stable transformants overexpressing 486/STOP and by administration of 486/STOP recombinant protein. Expression of 486/STOP was detected from total cell lysates, as well as conditioned media collected from stable transformants. In stable transformants, growth in monolayer was slightly retarded, and anchorage-independent growth in vitro and tumorigenicity in vivo were markedly inhibited. Addition of conditioned media from 486/STOP cells inhibited anchorage-independent growth of parental cells. Although tumorigenicity of parental cells in vivo was abrogated when they were cocultured in monolayer with 486/STOP cells over 48 h before injection to nude mice, coinjection of parental cells and 486/STOP cells without preculture was not successful. In contrast, administration of 486/STOP partially purified recombinant protein inhibited tumorigenicity of parental cells in vivo. Because 486/STOP cells result in massive apoptosis in vivo within 48 h, usage of a recombinant protein has a great advantage to use its unique bystander effect in vivo for clinical application.

Animals↗

Activated neutrophils and platelet microaggregates impede blood filterability through microchannels during simulated extracorporeal circulation.

BACKGROUND: Neutrophil sequestration and platelet microaggregates in organ capillaries have been implicated in the inflammatory response associated with cardiopulmonary bypass. We examined the filterability of neutrophils and platelet microaggregates through silicon microchannels during simulated extracorporeal circulation. We hypothesize that blood contact with artificial surfaces over time decreases the ability of neutrophils, platelets, and their aggregates to pass through microchannels. METHODS: Fresh human blood from donors (n = 9) was recirculated for 120 minutes in a simulated extracorporeal circuit. Blood samples were obtained from a donor at 0, 30, 60, and 120 minutes of recirculation. The microchannel transit time and the flow behavior of blood cells were evaluated by a silicon microchannel array flow analyzer. CD11b, L-selectin, and F-actin of neutrophils were measured by flow cytometry. Neutrophil and platelet counts and platelet aggregation to adenosine diphosphate were measured. RESULTS: The microchannel transit time was prolonged during recirculation, reaching 185.9% +/- 25.6% of baseline at 120 minutes. The video microscope showed that neutrophils and platelet microaggregates plugged the microchannels. CD11b, L-selectin, and F-actin levels changed significantly by 120 minutes. Platelet counts decreased and platelet aggregability was attenuated. CONCLUSIONS: Simulated extracorporeal circulation caused a progressive loss in the ability of neutrophils, platelets, and their aggregates to pass through the microchannels independent of neutrophil adhesion molecule expression.

Actins↗

ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation.

BACKGROUND: Among the serine proteases, neutrophil elastase is a powerful cytotoxic enzyme and plays a pivotal role in the inflammatory response associated with cardiopulmonary bypass. This study assesses the effects of the specific inhibition of neutrophil elastase by a novel, potent, low-molecular-weight neutrophil elastase inhibitor, ONO-6818. We hypothesized that ONO-6818 reduces inflammatory mediators and modulates adhesion molecules and the deformability of neutrophils during simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating fresh heparinized (3.75 U/mL) human blood for 120 minutes in a membrane oxygenator and a roller pump with and without 1.0 micromol/L of ONO-6818 (n = 9 for control group, n = 7 for ONO-6818 group). The neutrophil adhesion molecules, CD11b and L-selectin, and the cytoplasmic F-actin of neutrophils were measured by flow cytometry. Neutrophil deformability was evaluated using simulated silicon microcapillaries. Neutrophil elastase, interleukin 8, and C5b-9 were measured using enzyme immunoassay. RESULTS: Neutrophil elastase levels were significantly lower in the ONO-6818 group. ONO-6818 significantly reduced interleukin 8 and C5b-9 production. ONO-6818 did not modulate changes of CD11b and L-selectin during recirculation. Cytoplasmic F-actin content and changes of neutrophil deformability did not significantly differ between the groups. CONCLUSIONS: Inhibition of neutrophil elastase activity with ONO-6818 reduces further interleukin 8 production and the formation of the complement membrane attack complex, and this results in a reduction of neutrophil elastase levels during simulated extracorporeal circulation. This study suggests that specific neutrophil elastase inhibition with ONO-6818 is a feasible therapeutic option to attenuate the exaggerated inflammatory response associated with cardiopulmonary bypass.

Actins↗

Palliative open heart surgery in an infant with factor VII deficiency.

An infant with factor VII deficiency underwent palliative open heart surgery for pulmonary atresia with an intact ventricular septum. No references had been found on the management of this rare coagulation disorder in infantile cardiac surgery. We describe the peri- and postoperative management with a replacement therapy including a recombinant factor VIIa concentrate. We conclude that an appropriate replacement therapy is needed to control bleeding during open heart surgery with factor VII deficiency.

Cardiac Surgical Procedures↗

Phosphodiesterase type 4 inhibition of activated polymorphonuclear leukocytes in a simulated extracorporeal circulation model.

OBJECTIVES: Cardiopulmonary bypass is associated with a systemic inflammatory response syndrome and the risk of multiorgan injuries mediated by activated polymorphonuclear leukocytes. Phosphodiesterase type 4 is the predominant phosphodiesterase isozyme in polymorphonuclear leukocytes and plays a key role in the regulation of polymorphonuclear leukocyte activation. The aim of this study was to examine the effect of rolipram, a selective phosphodiesterase type 4 inhibitor, on the functional changes of polymorphonuclear leukocytes by using simulated extracorporeal circulation. METHODS: Simulated extracorporeal circulation was established by recirculating heparinized human blood for 120 minutes on a membrane oxygenator with and without 10 micro mol/L rolipram. F-actin content and L-selectin and CD11b expression of polymorphonuclear leukocytes were measured by means of flow cytometry. Polymorphonuclear leukocyte deformability was evaluated with a microchannel array flow analyzer that had a similar diameter as the capillaries. Polymorphonuclear leukocyte elastase was measured with an enzyme immunoassay. RESULTS: Rolipram reduced the increase of F-actin content of polymorphonuclear leukocytes and the increase of transit time of 100 micro L of blood sample through a microchannel. Rolipram reduced the increase of CD11b expression and the decrease of L-selectin expression of polymorphonuclear leukocytes. Rolipram reduced the release of elastase from polymorphonuclear leukocytes. CONCLUSION: Rolipram inhibited the deformability change mediated by F-actin assembly, the changes in adhesion molecules, and the release of elastase from activated polymorphonuclear leukocytes in simulated extracorporeal circulation. This study suggests that phosphodiesterase type 4 inhibition could be a feasible therapeutic strategy to prevent the exaggerated inflammatory response related to cardiopulmonary bypass.

3',5'-Cyclic-AMP Phosphodiesterases↗

Expression and potential roles of pregnane X receptor in endometrial cancer.

Estrogen has been shown to contribute greatly to growth and development in endometrial cancer. And recent research has suggested that intratumoral production of estrogen may play important roles in this cancer tissue. On the other hand, pregnane X receptor (PXR), a new member of nuclear receptors, has been shown to mediate the genomic effects of steroid hormones, including estrogen and xenobiotics. And this receptor is thought to regulate the expression of the cytochrome P-450 3A (CYP3A) gene family, which plays important roles in the metabolism of endogenous steroids and xenobiotics. Various levels of PXR expression were found in endometrial cancer tissues but not normal tissues. Tissues showing high PXR expression showed significantly high expression of CYP3A4/7 and low expression of estrogen receptor (ER) compared with levels in tissues showing low PXR expression. In endometrial cancer cell lines, HEC-1 cells, which express high PXR and low ER and progesterone receptor, show a stronger transcriptional response of the PXR-CYP3A pathway to the PXR ligands, especially endocrine-disrupting chemical, than do Ishikawa cells. These data suggest that the steroid/xenobiotics metabolism in the tumor tissue through PXR-CYP3A pathway might play an important role, especially in alternative pathway for gonadal hormone and endocrine-disrupting chemical effects on endometrial cancer expressing low ER alpha.

Aryl Hydrocarbon Hydroxylases↗