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Biomedical subjects

Y Fujii

Publications and source records attributed to Y Fujii.

At least 469 records · Page 26Linked to original sources

Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.

Animals↗

An immunocytochemical study of changes in the human erythrocyte membrane skeleton produced by stretching examined by the quick-freezing and deep-etching method.

A quick-freezing and deep-etching method in combination with erythrocyte splitting was used to examine the cytoplasmic aspect of whole-mount human erythrocyte membranes. Various external forces induced alterations in membrane skeletal organisation during the splitting procedure. The initial change was elongation in the peripheral part of the membrane skeleton, examined by immunostaining with a monoclonal antispectrin antibody. Under severe stretching conditions, a linear rearrangement of filamentous components was evident; these were disposed parallel to the rim of the erythrocyte, while the central part of the concavity exhibited a more compacted structure. These changes resulted in a different distribution of membrane skeletal components between central rigid and peripheral flexible areas in biconcave erythrocytes. It is suggested that the reversible membrane skeletal changes in the flexible areas which resist the external forces are important for maintaining the normal framework of biconcave human erythrocytes.

Antibodies, Monoclonal↗

Granisetron reduces the incidence of nausea and vomiting after middle ear surgery.

We studied the efficacy of granisetron, a selective 5-hydroxytryptamine type-3 receptor antagonist, in preventing postoperative nausea and vomiting (PONV) after middle ear surgery. In a randomized, double-blind, placebo-controlled study, 60 ASA I patients received placebo (saline) or granisetron 40 micrograms kg-1 i.v. immediately before induction of anaesthesia (n = 30 in each group). A standard general anaesthetic technique was used. During the first 24 h after anaesthesia, the incidence of PONV in patients who had received granisetron was lower than in those who had received placebo (17% vs 63%; P < 0.05). There were no clinically important adverse effects in either group. We conclude that granisetron, given before anaesthesia, reduced the incidence of PONV after middle ear surgery.

Adult↗

A simple method for recovering the motile spermatozoa from extremely low quality sperm samples.

Recovery of motile spermatozoa from extremely low quality samples for use in the intracytoplasmic sperm injection (ICSI) procedure is difficult. To solve this problem we developed a simple method to recover the motile spermatozoa using a 3% polyvinylpyrrolidone (PVP) droplet. After depositing a sperm pellet into this slightly viscous droplet, motile spermatozoa readily swam out to the clear area while immotile spermatozoa dispersed to a lesser extent, so that motile and immotile cells became clearly separated from each other. A total of 36 ICSI cycles using spermatozoa with extremely low quality characteristics were performed. We recovered the motile spermatozoa from all sperm samples from two sources of poor quality spermatozoa. Thirty-one cycles of ICSI with ejaculate resulted in fertilization and pregnancy rates of 54 and 29% respectively. Five cycles of ICSI with frozen-thawed epididymal spermatozoa resulted in fertilization and pregnancy rates of 70 and 60% respectively. The 3% PVP droplet method is very simple and easy to perform, so it may be useful for recovering the motile spermatozoa from extremely low quality sperm samples used for ICSI.

Cell Separation↗

Electron microscopic study of erythroblastic islands obtained by 'tissue-stamp culture' method.

A new 'tissue-stamp culture' method was developed for stamping proliferating erythroblasts of mouse spleens on collagen-coated coverslips after inducing haemolytic anaemia by administration of 1-acetyl-2-phenylhydrazine, and then adherent splenic cells were cultured for a few days. We could obtain many erythroblastic islands, where cultured erythroblasts were located over macrophages and were proliferated synchronously for 10-30 h, and then the erythroblasts were differentiated and enucleated after 30-50 h in the presence of erythropoietin. To observe three-dimensional structures of the erythroblastic islands, a scanning electron microscope was used for the cultured cells treated with critical point-drying method. Immature wrinkled erythroblasts with many micropinocytic pits were attached to the central area of the flattened macrophages with many cytoplasmic projections, though matured erythroblasts were localized on their peripheral areas. Moreover, cytoplasmic projections of underlying macrophages, which were attached to the matured erythroblasts, were decreased in number. At a late stage, deep cytoplasmic invaginations of erythroblasts observed at a middle stage became shallow after their enucleation and flattened to form their concave shapes. This 'tissue-stamp culture' system would be useful for studying specific interaction between stromal macrophages and haematopoietic cells.

Anemia, Hemolytic↗

The effects of dexamethasone on antiemetics in female patients undergoing gynecologic surgery.

UNLABELLED: This randomized, double-blind study compared the effects of dexamethasone plus either droperidol, metoclopramide, or granisetron with each antiemetic alone for preventing postoperative nausea and vomiting (PONV) in 270 female patients undergoing general anesthesia for major gynecological surgery. Patients were randomly assigned to receive either droperidol 1.25 mg (Group D1, n = 45), droperidol 1.25 mg plus dexamethasone 8 mg (Group D2, n = 45), metoclopramide 10 mg (Group M1, n = 45), metoclopramide 10 mg plus dexamethasone 8 mg (Group M2, n = 45), granisetron 40 micrograms/kg (Group G1, n = 45), or granisetron 40 micrograms/kg plus dexamethasone 8 mg (Group G2, n = 45) immediately before the induction of anesthesia. A standard general anesthetic technique and postoperative analgesia were used throughout the study. Complete response, defined as no PONV and no administration of rescue antiemetic medication during the first 24 h after anesthesia, was 49% in Group D1, 60% in Group D2 (P = 0.199 versus Group D1), 51% in Group M1, 62% in Group M2 (P = 0.198 versus Group M1), 80% in Group G1, and 96% in Group G2 (P = 0.025 versus Group G1). Our results suggest that dexamethasone enhances the antiemetic efficacy of granisetron but does not potentiate the other antiemetics-droperidol and metoclopramide-in female patients undergoing major gynecological surgery. IMPLICATIONS: We compared the efficacy of dexamethasone plus three different antiemetics-droperidol, metoclopramide, and granisetron-for the prevention of nausea and vomiting after gynecologic surgery. The granisetron-dexamethasone combination was the most effective for preventing post-operative emetic symptoms.

Adult↗

Detection of delayed cerebral vasospasm, after rupture of intracranial aneurysms, by magnetic resonance angiography.

OBJECTIVE: The goal of this study was to assess the value of magnetic resonance angiography (MRA), compared with conventional angiography, in the diagnosis and follow-up monitoring of delayed cerebral vasospasm after subarachnoid hemorrhage resulting from rupture of intracranial aneurysms. METHODS: For 32 patients undergoing examination by both MRA and conventional angiography during the period of risk for vasospasm, on the same day, the frequency and severity of and sequential changes in vasospasm were evaluated. The three-dimensional time-of-flight method was used. MRA was performed three times, i.e., before, during, and after the period of risk for vasospasm. Conventional angiography was performed twice, i.e., at admission and during the period of risk for vasospasm. Vasospasm was assessed at 22 regions of the cerebral arteries, including the bilateral anterior cerebral (A1, A2, and A3 segments), middle cerebral (M1, M2, and M3 segments), internal carotid (C1 and C2 segments), posterior cerebral (P1 and P2 segments), and posterior communicating arteries. RESULTS: Seven patients were excluded because of poor MRA images. Twenty-two of 25 patients (125 arteries) showed vasospasm in conventional angiograms. Nineteen of the 22 patients also showed vasospasm in MRA images; however, 57 arteries (45.6%) were diagnosed as showing vasospasm by MRA, and 59 (47.2%) could not be evaluated because of artifacts. For the remaining three patients (nine arteries, 7.2%), vasospasm could not be detected by MRA. Sequential changes in vasospasm could be well evaluated by MRA. CONCLUSION: MRA could be useful for management of cerebral vasospasm, although it cannot become a practical alternative to conventional angiography.

Adult↗

Involvement of Ca(2+)-calmodulin-dependent protein kinase II in the intestinal secretory action of Escherichia coli heat-stable enterotoxin II.

Treating the mouse intestine with the calmodulin antagonist W-7 and KN-93, an inhibitor of Ca(2+)-calmodulin-dependent protein kinase II (CaMK II), reduced the sensitivity of the host to the action of Escherichia coli heat-stable enterotoxin II (STII). CaMK II activity in mouse intestinal cells increased after exposure to STII. These results indicate that CaMK II is involved in the mechanism of action of STII.

Animals↗

Bacillus Calmette-Guérin enhances production and secretion of type IV collagenases in peripheral blood mononuclear cells.

Intravesical administration of bacillus Calmette-Guérin (BCG) is an effective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whether BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Production and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography, western blot analysis, and northern blot analysis. Invasion of bladder cancer cells was also examined using reconstituted basement membrane (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the production and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PBMCs may account in part for the effect.

Cells, Cultured↗

Granisetron reduces incidence of nausea and vomiting after breast surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) remains a troublesome problem. The study was performed to evaluate the antiemetic efficacy of prophylactic granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, on the incidence of PONV in patients undergoing general anaesthesia for breast surgery. METHODS: In a randomized, placebo-controlled, double-blind study, 50 female patients, 45-68 years, were given a single dose of either placebo (saline, n = 25) or granisetron (40 micrograms.kg-1, n = 25) intravenously over 2-5 min immediately before the induction of anaesthesia. Postoperatively, during the first 24 hours after anaesthesia, the incidence of PONV and adverse events was recorded. RESULTS: The treatment groups were similar for patient demographics, types of surgery, anaesthetic and postoperative management. Postoperatively, the incidence of PONV was 48% and 16% after administration of placebo and granisetron, respectively (P < 0.05). No differences in the incidence of other adverse events were observed between the two groups. CONCLUSION: Granisetron is an effective antiemetic for preventing PONV in patients undergoing general anaesthesia for breast surgery.

Aged↗

Effective dose of granisetron in the reduction of nausea and vomiting after breast surgery.

BACKGROUND: Prophylactic use of granisetron, a selective 5-hydroxytryptamine type 3 receptor antagonist, reduces the incidence of nausea and vomiting after breast surgery. This study was undertaken to determine the minimum effective dose of granisetron in the reduction of postoperative nausea and vomiting (PONV) in patients undergoing general anaesthesia for breast surgery. METHODS: In a randomized, double-blind manner, 120 female patients aged 42-66 years were assigned to receive either placebo (saline) or granisetron in a dose of 20 micrograms.kg-1, 40 micrograms.kg-1 and 80 micrograms.kg-1 i.v. immediately before the induction of anaesthesia. A standard general anaesthetic technique was employed throughout. The PONV and safety assessments were performed continuously during the first 24 h after anaesthesia. RESULTS: There were no significant differences among the groups with regard to patient demographics, surgical procedures, anaesthetics administered and analgesics given. The incidence of PONV was 47%, 43%, 17% and 17% after administration of placebo and granisetron 20 micrograms.kg-1, 40 micrograms.kg-1 and 80 micrograms.kg-1, respectively. Granisetron 40 micrograms.kg-1 was as effective as 80 micrograms.kg-1 and both resulted in significant reductions of the incidence of PONV compared with placebo and granisteron 20 micrograms.kg-1 (P < 0.05). No differences in the incidence of adverse events were observed among the groups. CONCLUSION: Granisetron 40 micrograms.kg-1 appears to be the minimum effective dose for reducing PONV in patients undergoing general anaesthesia for breast surgery.

Adult↗

Extracellular secretion of Escherichia coli heat-stable enterotoxin I across the outer membrane.

Escherichia coli heat-stable enterotoxin Ip (STIp) is an extracellular toxin consisting of 18 amino acid residues that is synthesized as a precursor of pre (amino acid residues 1 to 19), pro (amino acid residues 20 to 54), and mature (amino acid residues 55 to 72) regions. The precursor synthesized in the cytoplasm is translocated across the inner membrane by the general export pathway consisting of Sec proteins. The pre region functions as a leader peptide and is cleaved during translocation. However, it remains unknown how the resulting peptide (pro-mature peptide) translocates across the outer membrane. In this study, we investigated the structure of the STIp that passes through the outer membrane to determine how it translocates through the outer membrane. The results showed that the pro region is cleaved in the periplasmic space. The generated peptide becomes the mature form of STIp, which happens to have disulfide bonds, which then passes through the outer membrane. We also showed that STIp with a carboxy-terminal peptide consisting of 3 amino acid residues passes through the outer membrane, whereas STIp with a peptide composed of 37 residues does not. Amino acid analysis of mutant STIp purified from culture supernatant revealed that the peptide composed of 37 amino acid residues was cleaved into fragments of 5 amino acid residues. In addition, analyses of STIps with a mutation at the cysteine residue and the dsbA mutant strain revealed that the formation of an intramolecular disulfide bond within STIp is not absolutely required for the mature region of STIp to pass through the outer membrane.

Amino Acid Sequence↗

Protection of mice from respiratory Sendai virus infections by recombinant vaccinia viruses.

Mechanisms of protection of mice from Sendai virus, which is exclusively pneumotropic and causes a typical respiratory disease, by immunization with recombinant vaccinia viruses (RVVs) were investigated. Although the RVV carrying a hemagglutinin-neuraminidase gene of Sendai virus (Vac-HN) propagated in the noses and lungs of mice by either intranasal (i.n.) or intraperitoneal (i.p.) inoculation, no vaccinia virus antigens were detected in the mucosal layer of upper and lower airways of the i.p.-inoculated mice. The mice immunized i.n. with Vac-HN or Vac-F (the RVV carrying a fusion protein gene of Sendai virus) demonstrated the strong resistance to Sendai virus challenge both in the lung and in the nose, whereas the i.p.-immunized mice showed almost no resistance in the nose but showed a partial resistance in the lung. Titration of Sendai virus-specific antibodies in the nasal wash (NW), bronchoalveolar lavage (BAL), and serum collected from the Vac-F-immunized mice showed that the NW from the i.n.-immunized mice contained immunoglobulin A (IgA) antibodies but no IgG and the BAL from the mice contained both IgA and IgG antibodies. On the other hand, neither IgA nor IgG antibodies were detected in the NW from the i.p.-immunized mice and only IgG antibodies were detected in the BAL, although both i.n.- and i.p.-immunized mice exhibited similar levels of serum IgG, IgA, and neutralizing antibodies. The resistance to Sendai virus in the noses of i.n.-immunized mice could be abrogated by the intranasal instillation of anti-mouse IgA but not of anti-IgG antiserum, while the resistance in the lung was not significantly abrogated by such treatments. These results demonstrate that IgA is a major mediator for the immunity against Sendai virus induced by the RVVs and IgG is a supplementary one, especially in the lung, and that the RVV should be intranasally inoculated to induce an efficient mucosal immunity even if it has a pantropic nature.

Administration, Intranasal↗

Involvement of MAP kinase and c-fos signaling in the inhibition of cell growth by somatostatin.

Somatostatin significantly suppressed cell growth of the mouse insulinoma-derived cell line MIN6. MIN6 cells exhibited high-affinity binding of somatostatin with 50% inhibitory concentration value of 0.9 nM. RNA blot analysis revealed that MIN6 cells expressed only SSTR3 among the five somatostatin receptors so far identified. Treatment of MIN6 cells with somatostatin significantly reduced the serum-induced c-fos expression levels. On the other hand, somatostatin (100 nM) treatment of MIN6 cells cultured in medium containing 10% serum transiently increased c-fos expression levels to 282 +/- 4.7% and then significantly decreased them to 27 +/- 7.6% of the levels before treatment. Mitogen-activated protein (MAP) kinase activity transiently increased to 656 +/- 91.2% and decreased thereafter to 39 +/- 13.3% of the activity before the addition of somatostatin (100 nM) into the medium. In addition, the stimulatory effect of somatostatin on c-fos expression and MAP kinase activity (early effect) was not altered by pertussis toxin (PTX), whereas the suppressive effect of somatostatin on c-fos expression and MAP kinase activity (late effect) was mitigated by PTX. These findings suggest that an inhibition of c-fos expression mediated by cross talk between PTX-sensitive G protein signaling and receptor tyrosine kinase signaling is one of the mechanisms by which somatostatin inhibits cell growth in MIN6 cells.

Animals↗

Mature CD4 single positive thymocytes in human Thymoma: T cells may differentiate in the thymic epithelial cell tumor.

Human thymoma, which is occasionally associated with autoimmune disease, is a thymic epithelial cell tumor and often contains a large number of lymphocytes. In a previous study, we have shown that a proportion of CD4 single positive T cells in human thymomas lack CD3, suggesting immaturity. In this study, we focused on the rest of the CD4 single positive T cells in thymomas that expressed CD3/TcR alpha beta and investigated the maturity of single positive T cells by analyzing lymphocyte surface antigens and the cells' proliferative response to a mitogen. CD4 single positive cells that expressed CD3 or TcR alpha beta also expressed CD69 and had probably undergone positive selection in the tumor. Further, isolated CD4 or CD8 single positive cells from the thymomas responsed to a mitogen although at lower levels than the corresponding single positive cells in the peripheral blood. These results indicate that thymomas contain single positive T cells which have mature phenotype and proliferative ability, and suggest that T cells may differentiate in thymoma.

Adult↗

Ultrastructural study of axonal cytoskeletons in the optic nerve damaged by acutely elevated intraocular pressure using the quick-freezing and deep-etching technique.

The aim of this study was to examine the ultrastructure of axonal cytoskeletons in guinea pig optic nerve damage induced by acutely elevated intraocular pressure (IOP) employing the quick-freezing and deep-etching method. An IOP of 60 mm Hg was maintained for 4 h. The unmyelinated axoplasm of the optic nerve at the normal IOP was filled with longitudinally oriented neurofilaments and bundled microtubules, which were cross-linked by numerous cross-bridges. Membranous organelles, such as mitochondria and vesicles, were scattered in the axoplasm. These organelles were similarly interconnected with microtubules or neurofilaments by the cross-bridges. The unmyelinated axoplasm of the optic nerve following acutely elevated IOP was shown to include intraaxonal collections of various membranous organelles and reduction of microtubules and neurofilaments. The cross-bridges linking microtubules, neurofilaments and membranous organelles in such axoplasm appeared to be dramatically reduced in number. Thus, it is suggested that the ultrastructural changes of axonal cytoskeletons in some optic nerves following elevated IOP might include the reduction of microtubules, neurofilaments and their associated cross-bridges.

Animals↗