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Biomedical subjects

M Masuda

Publications and source records attributed to M Masuda.

At least 343 records · Page 19Linked to original sources

[M-VAC chemotherapy for advanced urothelial cancer--side effects and their management].

Since the M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin) regimen was reported by Sternberg in 1985, it has been widely accepted for the treatment of metastatic transitional cell carcinoma. This regimen has a significantly high response rate, but bone marrow suppression and gastrointestinal (GI) symptoms are inevitable. To complete this M-VAC regimen, preventive therapy for side effects is necessary. From November 1986 to March 1993, a total of 72 patients were admitted and received M-VAC therapy at our hospital. All of them had metastatic or invasive transitional cell carcinoma and they received a total of 163 complete courses of M-VAC therapy. We examined the side effects of this M-VAC regimen, and evaluated the effectiveness of colony-stimulating factor for prevention of granulocytopenia or granisetron for prevention of GI symptoms. Twenty-three patients (39 courses) were given recombinant colony-stimulating factor. This cytokine prevented the nadir of neutropenia and shortened the period to reach the nadir and period that the neutrophil count was below 1,000/mm3. Twelve patients (26 courses) were given granisetron, with significant reduction of the incidence of GI symptoms. These findings suggest that M-VAC therapy is effective and safe when used in combination with these drugs.

Adult↗

[A case of malignant hemangiopericytoma arising from the mediastinum accompanied by hepatocellular carcinoma].

A 65-year-old man was admitted to Oita Medical University Hospital with complaints of right back pain, diplopia and vertigo. A tumor, 33 x 25 mm, was found on the right lateral chest wall on admission. Chest X-ray film and chest CT scan showed a tumor, 50 x 30 mm, in the right posterior mediastinum. The chest wall tumor was diagnosed as malignant hemangiopericytoma by biopsy, and the same diagnosis was made for the mediastinal lesion by aspiration cytology. Brain MRI showed a mass at the skull base, which was found to be a metastatic bone tumor from the mediastinal malignant hemangiopericytoma. Abdominal CT scan showed a massive tumor, 65 x 60 mm, in the right lobe of the liver. The liver tumor was diagnosed as hepatocellular carcinoma by biopsy. Combination chemotherapy, employing cyclophosphamide, vincristine, pirarubicin and dacarbazine (DYVADIC), in conjunction with radiation therapy, produced no response. The patient died 5 months after admission. Malignant hemangiopericytoma arising from the mediastinum is uncommon. Thus, the clinical features of our case, as well as those of previously reported cases in Japan, are discussed herein.

Aged↗

[Nasal NK-cell lymphoma].

A 75-year-old man was admitted to our hospital on June 1st, 1993, because of nasal obstruction, epistaxis, fever, night sweats and weight loss. Examination disclosed a 2-cm white necrotic mass in the nasal septum, and a biopsy disclosed non-Hodgkin's lymphoma, diffuse, mixed-type. Imprint smears showed cytoplasmic azurophilic granules in the tumor cells. Dense granules were demonstrated by electron microscopy. The tumor cells were CD1-2+3-4-7+8-16+56+57-, and T cell receptor genes were in germline configuration. NK activity against K562 was strongly positive. Based on morphologic, phenotypic, immunogenotypic, and cytotoxic findings, the tumor cells seemed to be derived from activated NK cells. Because the tumor cells were positive for the EB virus and CD21 antigen, EB virus seemed to have infected CD21-positive NK cells and transformed them. MDR P-glycoprotein was also positive. This finding may explain why nasal lymphomas are resistant to chemotherapy and have a poor prognosis.

Cell Transformation, Viral↗

An immunohistochemical analysis for cancer of the esophagus using monoclonal antibodies specific for modified nucleosides.

BACKGROUND: Modified nucleosides such as 1-methyl-adenosine and pseudouridine exist as minute components of transfer ribonucleic acid (tRNA) and are excreted in the urine in large amounts in the presence of malignancy. Although use of these modified nucleosides as tumor markers has long been studied and many reports have detailed their relationship with malignant tumors and the urinary excretion of various modified nucleosides, there have been no reports on modified nucleosides in esophageal carcinoma. METHODS: Monoclonal antibody patterns against 1-methyladenosine and pseudouridine were studied in esophageal carcinoma, freshly resected esophageal carcinoma tissue specimens fixed in 10% neutral formaldehyde solution, embedded in paraffin, and sectioned for immunohistochemical study. Inhibition enzyme-linked immunosorbent assay (ELISA) was used to examine urinary excretion of these modified nucleosides in patients with esophageal carcinoma. RESULTS: Although rare in normal esophageal epithelium, these modified nucleosides were strongly stained in esophageal carcinoma cells. Most carcinoma cells exhibited a cytoplasmic pattern, although some cells at the infiltrating edge displayed a nuclear pattern. These modified nucleosides were intensely imaged in 11 of 12 cultured esophageal cell lines, the exception being one line that had a much longer doubling time. Using ELISA, urinary excretion of these modified nucleosides was found to be significantly higher in patients with esophageal carcinoma than in healthy subjects; such excretion correlated with carcinoma size and stage and tended to decrease after treatment. CONCLUSIONS: These findings indicate that the modified nucleosides 1-methyladenosine and pseudouridine may be useful as tumor markers for esophageal carcinoma.

Adenosine↗

Association of all three types of Fc gamma R (CD64, CD32, and CD16) with a gamma-chain homodimer in cultured human monocytes.

Receptors for the Fc region of IgG (Fc gamma R) on mononuclear phagocytes have been shown to play an important role in the removal of IgG-opsonized particles from the circulation. We found that all three types of Fc gamma R (CD64, CD32, and CD16) in cultured human monocytes are associated with the gamma-chain homodimer that is also present in the high affinity receptor for IgE. Immunoprecipitates of each of these Fc gamma R, prepared from 1% digitonin lysates of cultured human monocytes, incorporated phosphate into a gamma-chain homodimer when incubated with [gamma-32P]ATP. Fc gamma RII immunoprecipitates also incorporated phosphate into Fc gamma RII itself. When human alveolar macrophages were used, similar results were obtained. Although to a minor extent, each anti-Fc gamma R immunoprecipitate from freshly purified monocytes also coprecipitated gamma-chains. These Fc gamma R and gamma-chains did not constitute one large complex, because anti-Fc gamma RI or anti-Fc gamma RIII immunoprecipitates did not coprecipitate Fc gamma RII. In addition, F (ab')2 fragments of anti-Fc gamma R mAb bound to intact cells were recovered in the anti-gamma-chain immunoprecipitates but not in immunoprecipitates made with anti-Fc gamma RIII or anti-Fc gamma RII mAb. When recovery of radioactivity in anti-gamma-chain immunoprecipitates was compared with that in anti-mouse-Ig immunoprecipitates, approximately 25% of the Fc gamma RI and 20% of the Fc gamma RII expressed at the cell surface were associated with gamma-chains. The gamma-chains may play an important role in signal transduction via Fc gamma R in human macrophages.

Antibodies, Monoclonal↗

Tyrosine phosphorylation of a gamma-chain homodimer associated with Fc gamma RIII (CD16) in cultured human monocytes.

The efficient expression of transmembrane-anchored Fc gamma RIIIa requires the presence of other peptides, such as the gamma-chain of the IgE receptor I or the zeta-chain of the TCR. We found that Fc gamma RIIIa in cultured human monocytes is specifically associated with the gamma-chain homodimer, and that the gamma-chains in this complex are phosphorylated on tyrosine residues. Anti-Fc gamma RIII immunoprecipitates, which were prepared from 1% digitonin lysates of cultured human monocytes, incorporated phosphate into a homodimer consisting of two 14-kDa polypeptides when incubated with [gamma-32P]ATP. Identity of this co-associated structure of Fc gamma RIIIa as the gamma-chain dimer was confirmed by elution of the protein from the anti-Fc gamma RIII immunoabsorbent with 1% Nonidet P-40 detergent and reimmunoprecipitation with anti-gamma-chain antibody. Phosphoamino acid analysis showed that the gamma-chain exclusively contained phosphotyrosine. The gamma-chain was also phosphorylated when electropermeabilized cells were activated by cross-linking Fc gamma RIIIa. The gamma-chain may play an important role in signal transduction via Fc gamma RIIIa in human macrophages.

Cells, Cultured↗

A comparative study of the solution structures of tachyplesin I and a novel anti-HIV synthetic peptide, T22 ([Tyr5,12, Lys7]-polyphemusin II), determined by nuclear magnetic resonance.

The solution structure of tachyplesin I, which was isolated from membrane acid extracts of the hemocytes from the Japanese horseshoe crab (Tachypleus tridentatus), was determined by nuclear magnetic resonance (NMR) and distance geometry calculation. Tachyplesin I takes an antiparallel beta-sheet structure with a type-II beta-turn. Recently, among more than 20 synthetic peptides associated with tachyplesin and its isopeptide (polyphemusin), we found that a novel compound, which we designated as T22 ([Tyr5,12, Lys7]-polyphemusin II), strongly inhibited the human immunodeficiency virus (HIV)-1-induced cytopathic effect and viral antigen expression. The solution structure of T22 was investigated using NMR, and its secondary structure was confirmed to be similar to that of tachyplesin I. The anti-parallel beta-sheet structure and the several amino-acid side chains on the plane of the beta-sheet of T22 are thought to be associated with the expression of anti-HIV activity.

Amino Acid Sequence↗

A bispecific antibody enhances cytokine-induced killer-mediated cytolysis of autologous acute myeloid leukemia cells.

An anti-CD3 Fab' x anti-CD13 Fab' bispecific antibody (BsAb) was generated. This BsAb reacted with both CD3+ T cells and CD13+ acute myeloid leukemia (AML) cells. We investigated whether cytokine-stimulated peripheral blood mononuclear cells (PBMC) could lyse patient AML cells after addition of the BsAb. When interleukin-2 (IL-2)-stimulated PBMC were assayed for their cytotoxicity against 51Cr-labeled allogeneic and autologous CD13+ AML cells, their activity was markedly enhanced by the addition of the BsAb. PBMC stimulated with IL-2 plus anti-CD3 monoclonal antibody (MoAb) showed higher proliferative ability and higher cytotoxicity if this was expressed as lytic units per culture. IL-7-stimulated PBMC also exhibited enhanced cytotoxicity against CD13+ AML cells after addition of the BsAb. Ultrastructurally, CD13+ AML cells incubated with IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb showed apoptotic morphologic changes. A colony assay for AML blast progenitors showed that the colony formation of CD13+ AML cells was inhibited by the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC, and that this inhibition was further enhanced by the addition of the BsAb. A colony assay for normal bone marrow progenitor cells showed that the addition of autologous IL-2 plus anti-CD3 MoAb-stimulated PBMC and the BsAb inhibited the formation of granulocyte-macrophage colonies and mixed-cell colonies. However, the degree of inhibition was smaller than that for the AML blast colonies. Taken together, these findings suggest that this BsAb may be useful for ex vivo purging of CD13+ AML cells in autologous bone marrow transplantation.

Antibodies, Monoclonal↗

R56865, a Na(+)- and Ca(2+)-overload inhibitor, reduces myocardial ischemia-reperfusion injury in blood-perfused rabbit hearts.

The cardioprotective effects of R56865 were studied in isolated rabbit hearts, blood-perfused with a support rabbit system. The effect on ischemic injury was evaluated by comparing myocardial contracture and contents of ATP catabolites and of lactate during 60 min of normothermic ischemia in untreated hearts (group I) and in hearts treated with 0.63 mg/kg of R56865 starting 20 min before ischemia (group II; n = 5 in each group). R56865 delayed the onset, and decreased the extent of ischemic contracture, but had no effect on the myocardial content of ATP, of its catabolites of lactate. The effect on reperfusion injury was studied by monitoring left ventricular function during 80-min reperfusion after the 60-min ischemia in three groups (n = 6 in each): an untreated group (group I) and two groups treated with R56865 given either before (group II) or after ischemia (group III). Ultrastructural changes and cellular calcium distribution after reperfusion were also studied. R56865 improved the recovery of function and prevented contracture during reperfusion. Left ventricular end-diastolic pressure was 13.2 +/- 2.8 mmHg in group II and 31.3 +/- 8.1 mmHg in group III vs 45.0 +/- 2.6 mmHg in group I (P < 0.0001 for II vs I; P > 0.05 for III vs I). Left ventricular developed pressure, maximum dP/dt and minimum dP/dt recovered to 71.0 +/- 5.4%, 98.9 +/- 6.1%, 85.3 +/- 4.8% of baseline values, respectively, in group II, to 64.5 +/- 3.0% (P > 0.05), 76.8 +/- 3.0%, 70.2 +/- 4.0% in group III, vs 52.0 +/- 6.5%, 58.9 +/- 6.9% and 53.6 +/- 5.8% in untreated hearts (P < 0.05 for II or III vs I). Coronary flow was 24.5 +/- 2.2 ml/min and 19.8 +/- 1.8 ml/min in groups II and III vs 14.8 +/- 0.7 ml/min (P < 0.05) in the untreated group. On histology the myocardium in hearts treated either before or after ischemia was well protected and calcium distribution was almost normal after reperfusion, while in untreated hearts, most of the myocardium displayed irreversible damage accompanied by massive intracellular calcium accumulation. We conclude that R56865 could attenuate Ca(2+)-overload, thereby reducing myocardial ischemia-reperfusion injury after an extended period of ischemia.

Animals↗

Improvement of culture conditions for L-proline production by a recombinant strain of Serratia marcescens.

Serratia marcescens SP511 was previously reported to be an L-proline-producing strain that harbors a recombinant plasmid carrying the mutant type of the proline operon. This strain produced 65 g/L of L-proline in a medium containing 22% sucrose and urea after 5 d of incubation under the conventional culture conditions. We searched for more suitable culture conditions for more abundant L-proline production by SP511. To improve the supply of a nitrogen source to cells, ammonium was used instead of urea and fed to a culture under control of the pH of the medium. The concentrations of MgSO4 and K2HPO4 were increased, and in addition, sucrose was continuously added to the culture at a final concentration of 32%. Under these conditions, the cell amount was increased twofold over that under the previous conditions and L-proline production reached a maximum of more than 100 g/L after 4 d of incubation.

Ammonia↗

Trans-ventricular septal defect approach for resection of accessory mitral valve tissue.

Accessory mitral valve tissue is a rare cause of left ventricular outflow tract obstruction, which can be difficult to recognize. Surgical resection by the conventional transaortic approach with or without left atriotomy is extremely difficult in infants with a small aorta. When a ventricular septal defect is present, it may be the best way to approach the accessory mitral valve tissue, because the ventricular septal defect is located just in front of it. Five infants underwent resection of accessory mitral valve tissue together with repair of other intracardiac malformations. In 3 infants, resection of accessory mitral valve tissue was easily performed through the ventricular septal defect, which required enlargement in 2 patients.

Female↗

The effects of leukemia inhibitory factor and interleukin 6 on the growth of acute myeloid leukemia cells.

The effects of leukemia inhibitory factor (LIF) and interleukin 6 (IL-6) on blast progenitors from acute myeloblastic leukemia (AML) were examined using a blast colony assay in a serum-free culture system. LIF and IL-6 stimulated colony growth in 2 and 5, respectively, of 11 cases studied. The simultaneous addition of LIF with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3) or IL-6 produced a statistically significant increase of colony numbers in 3, 6 and 7 of 11 cases, respectively. Numbers of colonies increased significantly when IL-6 was added simultaneously with GM-CSF or IL-3 in 5 and 4 of 11 cases, respectively. LIF or IL-6 used in the primary culture did not significantly change the numbers of secondary colonies compared to GM-CSF. Previous exposure to LIF and IL-6 did not alter cellular phenotype or morphology, indicating that LIF and IL-6 did not induce the differentiation of fresh AML blasts.

Adult↗

The biased lamellipodium development and microtubule organizing center position in vascular endothelial cells migrating under the influence of fluid flow.

To analytically study the morphological responses of vascular endothelial cells (ECs) to fluid flow, we designed a parallel plate flow culture chamber in which cells were cultured under fluid shear stress ranging from 0.01 to 2.0 Pa for several days. Via a viewing window of the chamber, EC responses to known levels of fluid shear stress were monitored either by direct observations or by a video-enhanced time-lapse microscopy. Among the responses of cultured ECs to flow, morphological responses take from hours to days to be fully expressed, except for the fluid shear stress-dependent motility pattern change we reported earlier which could be detected within 30 min of flow changes. We report here that ECs exposed to more than 1.0 Pa of fluid shear stress have developed lamellipodia in the direction of flow in 10 min. This is the fastest structurally identifiable EC response to fluid shear stress. This was a reversible response. When the flow was stopped or reduced to the level which exerted less than 0.1 Pa of fluid shear stress, the biased lamellipodium development was lost within several minutes. The microtubule organizing center was located posterior to the nucleus in ECs under the influence of flow. However, this position was established only in ECs responding to fluid shear stress for longer than 1 h, indicating that positioning of the microtubule organizing center was not the reason for, but rather the result of, the biased lamellipodium response. Colcemid-treated ECs responded normally to flow, indicating that microtubules were not involved in both flow sensing and the flow-induced, biased lamellipodium development.

Animals↗

Establishment of a feline T-lymphoblastoid cell line susceptible to feline immunodeficiency viruses.

A feline T-lymphoblastoid cell line susceptible to feline immunodeficiency viruses (FIV) was established and designated as Yu-1 cells. Yu-1 cells continued to grow over one year with more than 100 successive passages in the presence of human recombinant interleukin-2. Surface antigens of Yu-1 cells were feline Pan-T+, CD4+, and CD8-. Susceptibility of Yu-1 cells to FIV strains were higher than that of the primary culture of the feline peripheral blood mononuclear cells, indicating that this cell line should be useful for isolation, propagation, and neutralization test of FIV.

Animals↗

Successful trimethoprim-sulfamethoxazole therapy in a patient with hyperimmunoglobulin E syndrome.

A male patient with hyperimmunoglobulin E syndrome is described. Recurrent lymphadenitis and cutaneous staphylococcal abscesses were resistant to various antibiotics, and chemotaxis and hydrogen peroxide production of polymorphonuclear leukocytes were impaired. Following trimethoprim-sulfamethoxazole therapy, he was free from the above infections, and impaired polymorphonuclear leukocyte functions recovered and serum IgE decreased to approximately one-fifth of its initial level. Subsequent irregular medications, however, resulted in impairment of polymorphonuclear leukocyte functions and an increased serum IgE concentration, which recovered after regular resumption of trimethoprim-sulfamethoxazole treatment. From these results, the beneficial effects of trimethoprim-sulfamethoxazole in hyperimmunoglobulin E syndrome are clinically apparent, but in vitro studies failed to demonstrate the positive effect of trimethoprim-sulfamethoxazole on polymorphonuclear leukocytes and their mechanism still remains to be elucidated.

Adolescent↗

[A case of cytomegalovirus pneumonia and Pneumocystis carinii pneumonia with lung cancer--diagnosis by the polymerase chain reaction].

A 64-year-old male was admitted to Oita Medical University Hospital because of primary lung cancer. After the anticancer chemotherapy, the patient developed a high fever. His chest X-ray showed diffuse reticular shadows bilaterally, which were considered to be a drug induced pneumonia, then pulse therapy with corticosteroid was performed. With this treatment, the diffuse reticular shadows disappeared. One month later, however, a severe interstitial pneumonia developed, and the patient died of respiratory failure. Autopsy findings demonstrated cytomegalovirus (CMV) and Pneumocystis carinni pneumonia. The polymerase chain reaction (PCR) for CMV in mononuclear cells in the blood was positive through out his hospitalization. In the sera, however, it was negative at the time of admission, then became positive 10 days before the onset of pneumonia. In addition, the PCR for P. carinni on the swab became positive as well. These results imply that PCR can be used for diagnosis of CMV and P. carinii infections from sera or swabs.

Cytomegalovirus Infections↗

Molecular breeding of a biotin-hyperproducing Serratia marcescens strain.

We previously reported that an acidomycin-resistant mutant of Serratia marcescens Sr41, SB304, and a mutant that was derived from SB304 and was resistant to a higher concentration of acidomycin, SB412, produced 5 and 20 mg of D-biotin, respectively, per liter of a medium containing sucrose and urea (N. Sakurai, Y. Imai, M. Masuda, S. Komatsubara, and T. Tosa, Appl. Environ. Microbiol. 59:2857-2863, 1993). In order to increase the productivity of D-biotin, the biotin (bio) operons were cloned from strains SB412, SB304, and 8000 (wild-type strain), and pLGM412, pLGM304, and pLGW101, respectively, were obtained through subcloning. These plasmids harbored 7.2-kb DNA fragments coding for the bioABFCD genes on a low-copy-number vector and were introduced into SB304, SB412, and 8000. Among the resulting recombinant strains, SB412(pLGM304) exhibited the highest D-biotin production (200 mg/liter) in the production medium. The plasmid was stably maintained in cells. Unexpectedly, SB412(pLGM412) grew very slowly, and the D-biotin productivity of this recombinant strain was not evaluated because pLGM412 was unstable.

Biotin↗