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Biomedical subjects

N Shoji

Publications and source records attributed to N Shoji.

At least 19 recordsLinked to original sources

Pre-emptive therapy against cytomegalovirus (CMV) disease guided by CMV antigenemia assay after allogeneic hematopoietic stem cell transplantation: a single-center experience in Japan.

From April 1998 to March 2000, a cytomegalovirus (CMV) antigenemia-guided pre-emptive approach for CMV disease was evaluated in 77 adult patients who received allogeneic hematopoietic stem cell transplantation at the National Cancer Center Hospital. A CMV antigenemia assay was performed at least once a week after engraftment. High-level antigenemia was defined as a positive result with 10 or more positive cells per 50 000 cells and low-level antigenemia was defined as less than 10 positive cells. Among the 74 patients with initial engraftment, 51 developed positive antigenemia. Transplantation from alternative donors and the development of grade II-IV GVHD were independent risk factors for positive antigenemia. Ganciclovir was administered as pre-emptive therapy in 39 patients in a risk-adapted manner. None of the nine low-risk patients with low-level antigenemia as their initial positive result developed high-level antigenemia even though ganciclovir was withheld. Only one patient developed early CMV disease (hepatitis) during the study period. CMV antigenemia resolved in all but two cases, in whom ganciclovir was replaced with foscarnet. In eight patients, however, the neutrophil count decreased to 0.5 x 10(9)/l or less after starting ganciclovir, including three with documented infections and two with subsequent secondary graft failure. The total amount of ganciclovir and possibly the duration of high-dose ganciclovir might affect the incidence of neutropenia. We concluded that antigenemia-guided pre-emptive therapy with a decreased dose of ganciclovir and response-oriented dose adjustment might be appropriate to decrease the toxicity of ganciclovir without increasing the risk of CMV disease.

Adolescent↗

Comparative multi-color flow cytometric analysis of cell surface antigens in bone marrow hematopoietic progenitors between refractory anemia and aplastic anemia.

Refractory anemia (RA) in myelodysplastic syndrome (MDS) without prominent dysplasia closely resemble the mild type of aplastic anemia (AA) in their hematological features. This sometimes makes it difficult to distinguish clearly between the two diseases. Using the multi-color flow cytometric technique, we compared cell surface antigen expression patterns on bone marrow hematopoietic progenitor cells which were isolated as a CD34 positive- CD45 dull positive with low side scatter intensity (CD34(+)CD45(dull+)SSC(low)) population in flow cytogram between RA (n=12) and AA (n=11). The antigens analyzed in CD34(+)CD45(dull+)SSC(low) mononuclear cells were: CD38 and CD71 for cell growth-related antigens, CD 33 and CD13 for myeloid and monocytoid lineage-associated antigens, CD7 and CD19 for lymphoid lineage, and CD14 for a monocytic lineage specific antigen. The percentages of CD34(+)CD45(dull+)SSC(low) cells in bone marrow non-erythroid mononuclear cells, and the expression frequencies of CD38, CD71, CD33 and CD13 antigens in CD34(+)CD45(dull+)SSC(low) progenitors were all significantly decreased in AA compared to normal bone marrows (n=7) (P<0.005). In contrast, in RA bone marrows the percentages of CD34(+)CD45(dull+)SSC(low) cells showed wide distribution and the cell surface antigen expression patterns varied among each case: some cases showed low frequencies of CD38 and CD71 expression as well as AA, whereas the others showed high expression frequency of specific antigen(s) which may reflect the clonal expansion of an abnormal clone in bone marrow. An MDS patient who had progressed from RA to RAEB showed further projecting pattern of expression of CD38 and CD33 in CD34(+)CD45(dull+)SSC(low) population in accordance with the disease progression. These data suggest that analysis of cell surface antigen expression patterns of CD34(+)CD45(dull+)SSC(low) progenitor cells by multi-color flow cytometry appears to be a useful method for qualitative and quantitative assessment of marrow progenitor states in AA and RA, therefore this method could be helpful for early detection of clonal evolution in MDS.

ADP-ribosyl Cyclase↗

Decline in antibiotic enzyme activity of neutrophils is a prognostic factor for infections in patients with myelodysplastic syndrome.

We used flow cytometry to measure the activities of cathepsin G and elastase. The activity of elastase in neutrophils from patients with myelodysplastic syndrome (MDS) was significantly lower than that in neutrophils from the control group (P<.001). Patients with low elastase activity were significantly susceptible to infection (P<. 05). Our study suggests that analyzing antibacterial enzymes is useful in evaluating the prognosis of patients with MDS.

Acute Disease↗

Use of real-time PCR to monitor human herpesvirus 6 reactivation after allogeneic bone marrow transplantation.

Reactivation of human herpesvirus 6 (HHV-6) is common following allogeneic marrow transplantation, however, little is known about the immune control and pathogenic potential of HHV-6 infection after transplantation. In order to determine whether reactivation of HHV-6 plays an important role in the development of complications in patients undergoing allogeneic bone marrow transplantation or not, we developed a very rapid quantification of viral DNA using a LightCycler. The amount of viral DNA was determined using a supernatant of a chronically infected cell line [TaY(OK)] which contains a known amount of viral DNA. Peripheral blood cells were collected from 5 patients undergoing allogeneic bone marrow transplantation once before transplant and once per week after transplant for 8-24 weeks. The real-time PCR system revealed that there was a linear correlation in the range of 101 to 105 molecules of reference. Using this system, we have found the presence of non-diagnosed HHV-6 reactivation as well as symptomatic infection, indicating the potential for routine implementation of this technology for laboratory diagnosis of HHV-6 infection. Our study shows that this method of rapid quantification of HHV-6 genomes by the real-time PCR using a LightCycler may be useful not only to understand the reconstitution of the immune system following marrow transplantation but also to manage the care of patients.

Adolescent↗

[Non-myeloablative stem cell transplant].

Myeloablation and immunosuppression were considered to be the two major roles of the conditioning regimens for allogeneic stem cell transplantation to facilitate engraftment. It has turned out, however, that immunosuppression is more important and myeloablation is not necessary for engraftment. At the same time, it is considered that the major anti-tumor effect of allogeneic stem cell transplantation depends on the graft-versus-leukemia effect, not on the conditioning regimen itself. In patients with CML who relapsed after allogeneic transplantation, for example, infusion of donor lymphocytes can induce a second complete remission. Non-myeloablative stem cell transplantation (NST) was developed in the late 90s based on these theories. Low-dose, less toxic, so-called "non-myeloablative" preparative regimens have been designed not to eradicate the malignancies, but to provide sufficient immunosuppression to allow donor cells to engraft, while the graft-versus-malignancy effects eradicate the tumor. This strategy permits allogeneic transplantation to be used in patients who are not eligible for conventional, often myeloablative, transplantation because of advanced age or organ dysfunction. Non-myeloablative preparative regimens contain purine analogs, such as fludarabine or cladribine. The NST regimen being used at the National Cancer Center Hospital, Tokyo, Japan, consists of cladribine (0.11 mg/kg x 6 days), busulfan (4 mg/kg x 2 days) and rabbit anti-thymocyte globulin (2.5 mg/kg x 4 days). We enrolled 6 patients in this NST protocol so far: 1 with severe aplastic anemia (sibling-PBSCT), 2 with MDS-RA (1 for sibling-PBSCT and 1 for matched uBMT), 1 with AML-CR2 (matched uBMT), 1 with AML-CR3 (sibling-PBSCT), and 1 with relapsed AML (mismatched related PBSCT). All patients achieved engraftment within 14 days with complete donor chimerism. In addition to leukemias, a graft-versus-malignancy effect was also reported in allogeneic NST of solid tumors, such as renal cell carcinoma and malignant melanoma. The long-term efficacy of NST remains to be determined, and further clinical trials are warranted.

Animals↗

Effects of endothelin receptor antagonists on anterior chamber inflammation induced by intravitreal injection of endothelin-1.

To investigate the role of endothelin receptors (ET(A) and ET(B)) in the inflammatory reaction induced by endothelin-1 (ET-1), the time course of changes in aqueous protein concentration (APC) after the intravitreal injection of ET-1 (10(-4), 10(-5) M) was measured using a laser flare-cell meter in pigmented rabbit eyes. The effects of pre-treatment with specific ET(A) receptor antagonist (97-139) (10(-1), 10(-2), 10(-3), 10(-4) M), specific ET(B) receptor antagonist (BQ-788) (1.6 x 10(-3) M), and vehicle solution were assessed. The influence of ET(A)receptor antagonist pre-treatment on aqueous prostaglandin E(2) and leukotriene B(4) concentrations was also evaluated. As a result, pre-treatment with ET(A) receptor antagonist blocked the APC increase induced by 10(-4) M ET-1 in a dose dependent fashion, while BQ-788 did not suppress the inflammatory reaction. The injection of ET-1 increased aqueous prostaglandin E(2) concentration, which was inhibited by pre-treatment with ET(A) receptor antagonist. Aqueous leukotriene B(4) concentration was not affected by ET-1 nor ET(A) receptor antagonist. In conclusion, ET(A) receptor mediates the increases in aqueous protein and prostaglandin E(2) concentration induced by ET-1 injection, and this inflammatory reaction occurs via the cyclooxygenase pathway of arachidonic acid cascade.

Animals↗

Influence of carbon dioxide on respiratory function during posterior retroperitoneoscopic adrenalectomy in prone position.

OBJECTIVE: To evaluate the influences of CO(2) insufflation on changes in blood gas analysis and end tidal CO(2) tension (PetCO(2)) during posterior retroperitoneoscopic adrenalectomy in the prone position. METHODS: Arterial blood gas analysis and measurements of PetCO(2) were carried out during CO(2) insufflation in 16 patients who underwent posterior retroperitoneoscopic adrenalectomy in the prone position (PRA group). The results were compared to 10 patients who underwent open posterior adrenalectomy (OPA group). Ventilation was artificially controlled during the study period in all cases. RESULTS: Arterial pH, PaCO(2), PetCO(2) and PaO(2) were not significantly different between the PRA and OPA groups. However, the PaCO(2)-PetCO(2) gradient in the PRA group was significantly higher than that in the OPA group (p < 0.01). CONCLUSION: Transperitoneal absorption of CO(2) occurs in patients undergoing retroperitoneoscopy in the prone position. The alveolo-arterial CO(2) gradient may be the only parameter which indicates the absorption of CO(2) during PRA.

Adrenal Gland Neoplasms↗

Microtubule and microfilament dynamics in rat embryos during the two-cell block in vitro.

Developmental block of rat embryo is induced by phosphate at the late two-cell stage. The present study uses immunocytochemistry and laser scanning confocal microscopy to examine microtubule and microfilament dynamics in blocked and nonblocked two-cell-stage rat embryos. Thin fibrous microtubules were distributed homogeneously in the cytoplasm in nonblocked embryos during the interphase of the two-cell stage and then translocated into mitotic spindles at the M-phase. In embryos blocked at the two-cell stage, much thicker fibrous microtubules were formed and distributed as rude meshwork structures in the cytoplasm. Microfilaments were distributed adjacent to nuclei and along the inside of the plasma membrane in nonblocked embryos during the two-cell stage, at M-phase, and at cleavage to the four-cell stage. In embryos blocked at the two-cell stage, however, microfilaments formed granules and dispersed in the cytoplasm. The distribution of microtubules and microfilaments changed relative to the occurrence of two-cell block. In summary, these results indicate that both microtubules and microfilaments are closely involved in the developmental block in two-cell rat embryos.

Actin Cytoskeleton↗

Pulmonary function after posterior retroperitoneoscopic surgery.

Pulmonary function tests were performed in 12 patients who underwent posterior retroperitoneoscopic surgery, before and on the 3rd and 7th days after operation. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FCV, vital capacity (VC), total lung capacity (TLC), residual volume (RV) and functional residual capacity (FRC) were not significantly different between before and after surgery. It is assumed that posterior retroperitoneoscopic surgery could be performed without impairment of pulmonary function after surgery.

Adrenalectomy↗

Inflammatory reaction via arachidonic acid cascade after intravitreal injection of endothelin-1.

PURPOSE: To investigate the characteristics of anterior chamber inflammatory reaction induced by intravitreal injection of endothelin-1 (ET-1). METHODS: The time course of changes in aqueous protein concentration (APC) after intravitreal injection of 10(-4), 10(-5), 10(-6) and 10(-7) M ET-1 into rabbit eyes was measured with a laser flare-cell meter. The influence of a topical diclofenac sodium (DFNa) pre- and post-treatment was assessed. Aqueous prostaglandin E2 and leukotriene B4 concentration was quantified using a radioimmunoassay technique. RESULTS: Intravitreal injection of 10(-4) and 10(-5) M ET-1 significantly increased APC, while 10(-6) and 10(-7) M ET-1 did not induce anterior chamber inflammation. After 10(-5) M ET-1 injection, APC reached a maximum at 4 h post-treatment and returned to a normal level 48 h after injection. Eyes treated with 10(-4) M ET-1 displayed a bi-phasic time course, with peak values observed 4 to 8 h as well as 48 h after administration. Pre- and post-treatment with topical DFNa completely suppressed the APC increase in the 10(-5) M ET-1 preparation, and considerably inhibited it in the 10(-4) M ET-1 preparation. After ET-1 injection, aqueous prostaglandin E2 concentration increased significantly, followed by an increase in APC. There were no changes in leukotriene B4 concentration. CONCLUSIONS: ET-1 induces anterior chamber inflammation via the cyclooxygenase pathway of the arachidonic acid cascade. The lipoxygenase pathway is not involved in this reaction.

Administration, Topical↗

Retroperitoneoscopic partial adrenalectomy using an endoscopic stapling device in patients with adrenal tumor.

We performed 15 retroperitoneoscopic partial adrenalectomies using an endoscopic stapling device to divide the normal adrenal tissue and adenoma. The mean operating time and mean blood loss were 162 (129-210) min and 12 (5-67) ml, respectively. In 1 patient (6.7%), a pneumothorax occurred at the end of the procedure due to injury of the medial crus of the diaphragm. However, the procedure was not subsequently converted to open surgery. These facts suggest that posterior retroperitoneoscopic partial adrenalectomy is a valuable addition to adrenal gland surgery.

Adrenal Gland Neoplasms↗

Acute onset of coagulopathy in a patient with Kasabach-Merritt syndrome following transurethral resection of bladder tumor.

We report an unusual case of Kasabach-Merritt syndrome in a 62 year-old woman with bladder tumor who suffered from acute consumption coagulopathy that increased the fibrinolytic activity due to the presence of a huge hemangioma in the upper and lower extremities. Two days after the transurethral resection of the solitary bladder tumor, serious hematuria and life-threatening disseminated intravascular coagulation developed. Following treatments with heparin and subsequent steroid treatment, hemorrhage and abnormal hemostatic values improved. It is suggested that extensive investigation of the coagulation system should be done in patients with giant hemangioma, particularly before a surgical procedure.

Acute Disease↗

Microscopic analysis of enzyme activity, mitochondrial distribution and hydrogen peroxide in two-cell rat embryos.

A developmental block is induced by phosphate in rat embryos at the late two-cell stage. The present study was designed to examine the energy metabolism of rat two-cell blocked and non-blocked embryos. Enzyme activity was measured in individual embryos by histochemical techniques. The activities of malate dehydrogenase, isocitrate dehydrogenase, lactate dehydrogenase, pyruvate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, glutamate dehydrogenase, glucose-6-phosphate dehydrogenase, glucose-6-phosphatase, and phosphorylase did not differ among non-blocked and blocked embryos. However, the activity of succinate dehydrogenase was significantly decreased in blocked embryos compared with non-blocked embryos. In blocked embryos, cytochrome oxidase activity was distributed homogeneously, but was located at the perinuclear region in non-blocked embryos. Active mitochondrial organization was visualized using the fluorescent probe rhodamine 123 and laser scanning confocal microscopy. In both non-blocked and blocked embryos, mitochondria were distributed homogeneously. The concentration of H2O2 measured fluorometrically in embryos cultured without phosphate did not change significantly during the culture period, but decreased in embryos cultured with phosphate. The timing corresponded to the occurrence of the two-cell block. In summary, these results suggest that the developmental block in rat two-cell embryos is induced by disturbance of mitochondrial energy metabolism.

Animals↗

Possible application of transmitted laser light for the assessment of human pulpal vitality.

The purpose of this study was to determine whether use of transmitted laser light would enable a better assessment of human pulpal vitality than back-scattered light does (LDF: laser Doppler flowmetry). The experiments were carried out on ten upper central incisors in six subjects aged 23-28 years; five of the teeth were vital with no restoration, and five were non-vital. For use with transmitted laser light, the fibers within the probe of a conventional LDF apparatus were used, one for transmitting light onto the buccal surface, the other for receiving it at the palatal surface of the same tooth. For LDF, the probe was fixed at the buccal surface. Blood flow was measured at three different locations on each experimental tooth: the incisal third, the center and the cervical third of the tooth crown. In non-vital teeth, 1) output signals with transmitted laser light all registered zero, and no oscillation could be seen in recordings from any location on the tooth, but 2) LDF signals were above zero, there were regular oscillations related to heart rate, and passive increases in blood flow (corresponding to blood pressure increases) were recorded from both the center and the cervical third of the tooth, indicating that LDF registered blood flow of non-pulpal origin. In vital teeth, LDF signals were significantly higher than in non-vital teeth at each location on the tooth. At the central site on vital teeth, the output signals for transmitted laser light were about twice those seen with LDF, and passive blood flow changes corresponding to blood pressure increases were more clearly observed. These results indicated that transmitted laser light would be useful for the assessment of tooth pulp vitality both because the blood flow signals did not include flow of non-pulpal origin, and because its output signals and response to blood flow changes were clear and could easily be monitored.

Dental Pulp↗

[Anterior chamber inflammation after the injection of endothelin-1 into the vitreous and the effect of an anti-prostaglandin agent].

We measured the time course of aqueous protein concentration (APC) with a laser flare-cell meter after the injection of endothelin-1 (ET-1) into the vitreous cavity of pigmented rabbits and investigated the influence of pre- or post-treatment with an anti-prostaglandin agent on these effects of ET-1. Injection of ET-1 significantly increased APC in a dose-dependent fashion. After 10(-5)M ET-1 injection, APC reached maximum at 4 hours after treatment and returned to the normal level 24 hours after the injection. On the other hand, the 10(-4)M ET-1 model displayed a bi-phase time course, with a peak value observed at 4 approximately 8 hours and 48 hours post-treatment, and APC did not return to normal even 7 days after treatment. Treatment with anti-prostaglandin agents before and after the injection blocked APC increase completely in the 10(-5)M ET-1 model, and partially in the 10(-4)M ET-1 model. These results indicate that ET-1 effects on APC are at least partially mediated by the cyclooxygenase pathway of the arachidonic acid cascade.

Animals↗

[Anterior chamber inflammation after the injection of endothelin-1 into the vitreous and the effect of ETA receptor antagonist].

To assess the receptors which mediate the inflammatory reaction induced by endothelin-1 (ET-1), we investigated the influence of pre-treatment with an ETA receptor antagonist (97-139) on the increase of aqueous protein concentration (APC) after the injection of ET-1 (10(-4), 10(-5)M) into the vitreous cavity of pigmented rabbits. The concentration of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the aqueous humor after the injection of 10(-4)M ET-1 with or without pre-treatment with 97-139 (10(-1), 10(-2), 10(-3)M) was also studied. Pre-treatment with 10(-2)M and 10(-1)M 97-139 completely prevented the APC increase induced by 10(-5)M and 10(-4)M ET-1, respectively. Increases in aqueous PGE2 concentration were observed after the injection of ET-1, which was inhibited by pre-treatment with 97-139. Aqueous LTB4 concentration was not changed significantly by ET-1. These results indicate that the effects of ET-1 on APC are at least partially mediated by the cyclooxygenase pathway of arachidonic acid cascade, and that ETA receptors play an important role in these reactions.

Animals↗