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Biomedical subjects

S Fujii

Publications and source records attributed to S Fujii.

At least 91 records · Page 5Linked to original sources

Effects of nonionic contrast media on platelet aggregation: assessment by particle counting with laser-light scattering.

Intravascular radiographic contrast media used in angiography, particularly nonionic contrast media, may cause activation of platelets. This study was designed to determine which properties of nonionic contrast media were potentially responsible for this action. Platelet aggregation after adenosine diphosphate stimulation was studied in the platelet rich plasma obtained from 37 patients who underwent left ventriculography using the highly sensitive method of particle counting with laser-light scattering. Platelet activation by contrast media was studied in the platelet rich plasma from healthy volunteers using flow cytometric analysis to detect platelet degranulation as P-selectin expression. There was a significant decrease in platelet aggregation in patients injected with ioxilan or iomeprol compared with patients injected with iohexol. There was a significant increase in P-selectin expression with the three groups of contrast media compared to control. The platelet activation with ioxilan or iomeprol was significantly less compared to the activation with iohexol. The comparison showed that previous generalization regarding platelet activation by nonionic contrast media might not be valid. It is presumed that the higher osmolality of iohexol may contribute to the increase in platelet aggregation and activation.

Angiography↗

The temperature-dependent modulation of an inhibitory circuit in hippocampal slices as revealed by a population spike recording is mediated by extracellular adenosine.

We examined the effects of temperature on excitatory synaptic transmission and the recurrent inhibitory loop in CA1 neurons in guinea pig hippocampal slices. Increasing the temperature of the perfusing medium from 30 to 49 degrees C resulted in attenuation of both the amplitude of the synaptically evoked CA1 population spikes and the paired-pulse inhibition (PPI) of the spikes. A bath application of 2 microM picrotoxin, a gamma-aminobutyric acid receptor antagonist, did not affect the amplitude of the CA1 population spikes, but it significantly reduced PPI during the early heating phase (30-32 degrees C). In contrast, the application of 1 mM theophylline or 50 microM 8-phenyltheophylline, a selective adenosine A1 receptor antagonist, resulted in significant augmentation of the PPI during the early phase of hyperthermia (30-34 degrees C) and a significant increase in the amplitude of the CA1 population spikes at higher temperatures (34-43 degrees C). These results suggest that increased activation of adenosine A1 receptors in response to a temperature increase depresses not only excitatory synaptic responses, but also the strength of the inhibitory circuit in CA1 neurons. Furthermore, hyperexcitability of CA1 pyramidal neurons was seen in the middle of the heating range (34-38 degrees C), excitatory responses still being present, but the strength of the inhibitory circuit significantly reduced.

Animals↗

Clinical value of positron emission tomography with FDG for recurrent ovarian cancer.

OBJECTIVE: Recurrence is often a major problem for patients who have undergone surgery for ovarian cancer. This prospective study was undertaken to evaluate the clinical contribution of positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) for recurrent ovarian cancer. SUBJECTS AND METHODS: Twenty-four women who had undergone surgery or chemoradiotherapy for histopathologically proven ovarian cancer were enrolled in this study. Ovarian cancer was thought to have recurred in 12 of these women because of evidence on conventional imaging modalities or tumor marker measurements (group A). Clinical findings for the remaining 12 women showed them to be disease-free (group B). PET findings for the women were compared with the final diagnoses obtained by histopathology or by clinical follow-up. The clinical contribution of PET was assessed by evaluating whether PET yielded information complementing the findings of conventional modalities and by examining its impact on treatment. RESULTS: PET gave valuable information for seven of 12 patients in group A in addition to the information obtained from findings on conventional imaging, and treatment was affected in five patients. On the other hand, in group B, additional information was obtained in only three of 12 patients, and treatment of only one patient was affected. Overall sensitivity, specificity, and accuracy of conventional imaging modalities were 72.7%, 75.0%, and 73.3%, respectively, and these rates improved to 92.3%, 100.0%, and 94.4%, respectively, by considering both conventional imaging modalities and PET findings. CONCLUSION: Our preliminary data suggest that whole-body PET with FDG can be a complementary modality for following up patients who have had ovarian cancer, especially patients believed to be at risk for recurrence.

Case-Control Studies↗

Sodium sensitivity related to albuminuria appearing before hypertension in type 2 diabetic patients.

OBJECTIVE: To find whether sodium sensitivity of blood pressure appears before hypertension and whether the sensitivity is related to diabetic nephropathy, we examined type 2 diabetic patients with normal levels of serum creatinine. RESEARCH DESIGN AND METHODS: A total of 32 patients were divided into three age-matched groups: 11 patients had normoalbuminuria, 12 had microalbuminuria, and 9 had macroalbuminuria. Patients stayed on a diet with ordinary sodium levels for 1 week and a sodium-restricted diet for 1 week, in random order. Urinary excretion of sodium and albumin and systemic blood pressure were measured daily. A pressure-natriuresis curve was drawn by linkage of the two datum points obtained in the steady state during the different diets. We calculated the sodium sensitivity index as the reciprocal of the slope of this curve. RESULTS: The median sodium sensitivity index and the mean blood pressure were higher in micro- and macroalbuminuric patients than in normoalbuminuric patients. Eighteen patients were without hypertension (<140/90 mmHg); of these, 10 had blood pressure readings <130/85 mmHg with ordinary sodium levels. Urinary albumin was correlated with the index but not with blood pressure. For these 10 patients, the index in those with albuminuria was higher than in those with normoalbuminuria. In such patients with albuminuria, sodium restriction decreased albuminuria and blood pressure. CONCLUSIONS: In type 2 diabetic patients with albuminuria but normal levels of serum creatinine, sodium sensitivity of blood pressure appears before hypertension and is related to albuminuria; sodium restriction is one treatment for diabetic nephropath, even without hypertension.

Adult↗

Treatment of post-transplanted, relapsed patients with hematological malignancies by infusion of HLA-matched, allogeneic-dendritic cells (DCs) pulsed with irradiated tumor cells and primed T cells.

Patients with hematological malignancies who relapse after bone marrow transplantation (BMT) are often treated with donor lymphocyte infusion. However, this procedure often results in graft-versus-host disease (GVHD). While, Dendritic cells (DCs), which present antigens to naive T cells, have been used in the immunotherapy of cancer, this approach has been logistically difficult due to limiting numbers of DCs. We have now developed a method for obtaining a large number of DCs by treating the granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood stem cells (PBSCs) from healthy donors with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-4 (IL-4), and tumor necrosis factor-alpha (TNF-alpha). The resulting cells possess the morphologic, phenotypic, and functional characteristics of mature DCs. In in vitro studies, culture of these HLA-matched donor derived-DCs with irradiated each patient's tumor cells as an antigen source, followed by incubation with T cells from the patient, induced the production of highly cytotoxic T lymphocytes (CTLs) specific for the respective tumor cells in the semi-allogeneic setting. A transient, but objective clinical response was obtained in the absence of GVHD when we injected the DCs which had been pulsed with irradiated tumor cells as well as primed T cells from the same original donor of related- allogeneic stem cell transplantation into the relapsed patients. Our findings suggest that treatment of relapsed patients with such donor-derived DCs, and primed T cells may be effective as an adjunctive immunotherapy.

Adult↗

[T-cell prolymphocytic leukemia complicated by diffuse large B-cell lymphoma of the stomach].

We describe a case of T-cell prolymphocytic leukemia (T-PLL) in a 76-year-old man, who developed diffuse large B-cell lymphoma (DLBL) of the stomach, a previously unreported occurrence. The patient was referred to our hospital because of marked leukocytosis (40,000/microliter) without clinical symptoms. He was diagnosed as having T-PLL on the basis of the characteristic cell morphology and immunophenotype (CD2+, CD3+, CD4+, CD5+, CD7+, CD8-, CD25-, TCR alpha/beta+), but cytogenetic analysis showed no abnormalities. Fifteen months later, he developed a gastric tumor. Biopsy of the tumor revealed DLBL without features of MALT lymphoma; Helicobacter pylori was not detected. Chemotherapy eradicated the tumor, whereas the T-PLL was resistant to the therapy. The disease showed an indolent course for about 2 years thereafter. Immunological derangement due to T-PLL might have potentiated the development of DLBL in this case.

Aged↗

[A case report of total repair in a 71-year-old patient with tetralogy of Fallot].

A 71-year-old male is presented as ever the oldest patient of tetralogy of Fallot who underwent successful radical surgery. Heart murmur was pointed out at the age of 10 years. The patient consulted us because of dyspnea and cough, and was noted to have cyanosis and clubbing fingers. Polycythemia was also detected by hemoglobin of 20.8 g/dl and hematocrit of 58.4%, and a low PaO2 of 48.5 mmHg at room temperature was pointed out. Preoperative echocardiography and cardiac catheterization indicated a ventricular septal defect, overriding of the aorta, and right ventricular outflow tract stenosis with a pressure gradient of 115 mmHg between the right ventricle and the main pulmonary artery. Under cardiopulmonary bypass, the ventricular septal defect was closed with a dacron patch and the right ventricular outflow tract was enlarged by a patch of collagen-coated vascular graft with a commissurotomy of the pulmonary valve. Postoperatively, cyanosis disappeared and the pressure gradient was decreased to 26 mmHg.

Aged↗

[Results of questionnaire on open disclosure to patients with malignant lung tumors comparison of responses before and after chemotherapy].

To investigate patient attitudes towards open disclosure of malignant disease, we conducted a questionnaire survey of 17 patients with malignant lung tumors, to whom the nature of their disease was revealed. The questionnaire used a 100 mm analog scale. Ten of the patients were treated by chemotherapy and their questionnaire results before and after treatment were compared. It was found that they were mostly satisfied about being truthfully informed and that, indeed, they were anxious to know their true diagnoses. They were also keen to have their true prognosis revealed, but not as much as the diagnosis. They also wished to be informed about treatment and its effects. These attitudes showed no marked changes resulting from the administration of chemotherapy, and we therefore concluded that chemotherapy itself had no influence on patients' feelings about disclosure. The questionnaire was well accepted and was useful in judging attitudes to open disclosure.

Female↗

Mixed allogeneic chimerism with wild-type strains ameliorates atherosclerosis in apolipoprotein E-deficient mice.

Atherosclerosis involves inflammatory processes between vascular tissues and hematocytes with a hyperlipidemic background. To examine whether variations of hematocytes constitute one of the genetic components in atherosclerosis, irradiated apolipoprotein E (apoE)-deficient (apoE(-/-)) mice with hypercholesterolemia and preexisting atherosclerotic lesions were reconstituted with mixed bone marrow cells (BMC) from syngeneic and wild-type (apoE(+/+); atherosclerosis-resistant SJL or -susceptible B10.S) mice. Stable mixed allogeneic chimeras with small amounts of serum apoE were established without any detrimental complications. Compared with untreated apoE(-/-) mice or apoE(-/-) mice transplanted with syngeneic BMC alone, significant reduction of the cholesterol level and significant lesion regression were observed in the mixed chimeras. Furthermore, mixed chimeras given SJL BMC showed marked reductions in numbers of lesions compared with those reconstituted with B10.S BMC. Cholesterol levels in the former SJL chimeras, however, were significantly higher than those in the latter B10.S chimeras. These findings indicate that the resistance of SJL to atherosclerosis resides in the bone marrow-derived cells.

Animals↗

Water quality characteristics of forest rivers around Lake Biwa.

Forest river surveys were carried out at upper streams of several rivers in the Lake Biwa watershed to understand the water quality characteristics of the rivers, and to find out their relationships with forest features such as geographical, geological and vegetational data. The results showed: (1) Forests have some purification functions for nitrogen and organic matter, but become sources for most of ionic species. (2) Main mineral species in forest rivers are Ca2+, Mg2+ and Na+, HCO3-, CO3(2-), Cl-, SO4(2-) and SiO2. (3) Loading from forests was 0.4-7 kg/km2/d for TN and 0.01-0.3 kg/km2/d for TP. (4) River quality reflects the properties of each forest, and is unique to the place, especially in ionic species such as Ca2+ and Cl-. (5) A cluster analysis successfully categorized ionic components into several groups.

Ecosystem↗

Preparation and characterization of SNO-PEG-hemoglobin as a candidate for oxygen transporting material.

Acellular hemoglobin (Hb) derivates developed as oxygen carriers are known to cause hypertensive reactions due to their nitric oxide (NO) scavenging action. To modulate this undesired activity, we have developed a new Hb derivative, s-nitrosylated polyethylene glycol (PEG)-modified hemoglobin (SNO-PEG-Hb), which can deliver oxygen and NO. After human Hb was modified with PEG to increase its molecular weight, the free sulfhydryl groups of Hb were s-nitrosylated with s-nitrosoglutathione. Administration of unmodified Hb into anesthetized rats caused a hypertensive reaction, while s-nitrosylated Hb derivatives such as SNO-Hb and SNO-PEG-Hb did not raise blood pressure. The plasma half-lives of heme and NO bound to SNO-PEG-Hb were 11.5 and 2.4 hours respectively, indicating that the s-nitrosylated Hb derivative may act as a slow-releasing agent for NO. Based on these findings, SNO-PEG-Hb is a useful candidate for a blood substitute and tool for oxygen therapeutics.

Analysis of Variance↗

Evaluation of immunoglobulin G and its subclasses in aplastic anemia.

We selected 31 patients with aplastic anemia to measure their total immunoglobulin (Ig) G and IgG subclasses and compared the results obtained with those obtained in the normal control group (n=461). Patients with aplastic anemia were classified into three subgroups according to severity: mild subgroup (n=14), moderate subgroup (n=12) and severe subgroup (n=5). The decrease in total IgG was recognized in all these three subgroups (p<0.001). Although IgG1 decreased in severe subgroup (p<0.01), it showed no significant difference in mild and moderate subgroups. The decrease in IgG2 and IgG3 was observed in all these three subgroups (p<0.001 and p<0.01, respectively). Although IgG4 decreased in mild subgroup (p<0.05), it showed no significant difference in moderate and severe subgroups. We speculated that the measurement of IgG subclasses was useful in understanding the pathophysiology of humoral immunity in aplastic anemia.

Adult↗

Attenuation of hypothermia-induced platelet activation and platelet adhesion to artificial surfaces in vitro by modification of hemoglobin to carry S-nitric oxide and polyethylene glycol.

Hypothermic cardiopulmonary bypass alters platelet function and hypothermia is associated with postoperative myocardial ischemia. Thrombogenic surfaces such as extracorporeal circuits, vascular graft materials, and components of atherosclerotic plaque induce activation of platelets. The effects of human hemoglobin (Hb) covalently modified to carry S-nitric oxide (NO) functional groups (SNO-Hb), polyethylene glycol (PEG-Hb), and SNO-PEG-Hb on platelet activation were studied. Platelet activation was assessed by cytometric analysis of GPIIb-IIIa activation and P-selectin expression at hypothermic condition (22 degrees C) after stimulation with Hb derivatives. Platelet adhesion and aggregation were measured in a parallel glass plate chamber coated with unmodified Hb, SNO-Hb, PEG-Hb, SNO-PEG-Hb, and collagen. Platelet binding of antibodies to GPIIb-IIIa and P-selectin was significantly enhanced by hypothermic condition and by unmodified Hb. There was significantly less platelet binding of antibodies to GPIIb-IIIa and P-selectin with SNO-Hb, PEG-Hb, and SNO-PEG-Hb compared with unmodified Hb. There was significantly less platelet attachment, adhesion, and aggregation on the SNO-Hb, PEG-Hb and SNO-PEG-Hb coated surfaces compared with unmodified Hb-coated and -uncoated surfaces. SNO-Hb, PEG-Hb, and SNO-PEG-Hb induced less platelet activation at hypothermic temperature, and induced less platelet adhesion and aggregation on thrombogenic surfaces compared with unmodified Hb. The inhibitory effect may be derived from antiadhesive properties of Hb, antiplatelet actions of NO, and molecular barrier action of PEG.

Adult↗

Isolation and piezoresponse of the rpoA gene encoding the RNA polymerase alpha subunit from the deep-sea piezophilic bacterium Shewanella violacea.

The rpoA gene encoding the alpha subunit of RNA polymerase from the deep-sea piezophilic bacterium Shewanella violacea DSS12 was cloned and sequenced. The rpoA gene was found to encode a polypeptide consisting of 329 amino acids with a molecular mass of 36238 Da. S. violacea alpha protein was expressed in a ts Escherichia coli mutant, to confirm whether the rpoA gene is functional. It complemented this mutation, indicating a chimeric RNA polymerase is assembled at the non-permissive temperature. Recombinant alpha protein was overexpressed using an expression plasmid harboring the rpoA gene and purified to near homogeneity. Primer extension analysis revealed that two transcriptional initiation sites are recognized by sigma(70) RNA polymerase. It also indicated that pressure response (piezoresponse) in the alpha operon occurred at the transcriptional level, suggesting some positive regulators may interact with the transcriptional apparatus and regulate the expression of the operon at different pressure conditions.

Amino Acid Sequence↗

Enhancement of antitumor effect of bleomycin by low-voltage in vivo electroporation: a study of human uterine leiomyosarcomas in nude mice.

Uterine leiomyosarcoma is an extremely malignant neoplasm with high rates of distant metastasis, and systemic chemotherapy is not particularly effective. Thus, the introduction of more active anticancer agents, or of a new drug delivery system, is urgently needed. Recently, electrochemotherapy has been introduced as a way of enhancing the cytotoxic effects of chemotherapeutic agents. This involves administering the drug in combination with electric pulses (which permeabilize tumor cell membranes and allow the drug to enter the cells). In particular, bleomycin (BLM) cannot cross the plasma membrane efficiently, but its cytotoxicity can be enhanced by electropermeabilization. The aim of the present study was to investigate the effect of low-voltage electroporation (EP) in combination with local BLM injection on the growth of uterine leiomyosarcoma in nude mice. Human uterine leiomyosarcoma cells (SK-LMS-1) were implanted subcutaneously into nude mice. Tumor growth in mice treated with EP (100 V/cm) plus BLM was compared with that in mice receiving BLM alone, EP alone, or no treatment (controls). Tissue BLM concentrations and histological analysis (including mitotic counts) were evaluated in tumor tissues. There was a significant reduction in tumor growth in mice that received EP with BLM. One hour after the treatment, the local BLM concentration was 10 times higher in the tumors that received EP with BLM than in those receiving only BLM. Moreover, the mitotic count was lower in the tumors that received EP plus BLM than in the controls. These results demonstrate the possible therapeutic value of low-voltage EP with BLM in human uterine leiomyosarcoma.

Animals↗