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Biomedical subjects

Y Maeda

Publications and source records attributed to Y Maeda.

At least 361 records · Page 20Linked to original sources

[Combined hepatic resection and removal of portal vein tumor thrombi].

Portal thrombectomy with extended hepatectomy for extensively progressive primary liver cancer (Vp 3), in which the tumor thrombus has spread beyond the first portal branches, will make other non-surgical treatments possible and improve patients quality of life. We have performed extensive resections in 15 cases of such Vp 3 liver cancer. One patient with huge HCC involving retrohepatic IVC underwent in situ extended left hepatectomy without reconstruction of IVC, resulting in postoperative renal failure because of thrombosis in the bilateral renal veins, but 14 other patients' postoperative courses were uneventful. Ten of 14 patients relapsed within one year, but these patients underwent non-surgical treatments, resulting in improvement in the quality of life. The 1-, and 3-year survival rates were 55.6% and 32.5%, respectively.

Adult↗

[Chronic progressive radiation myelopathy after bone marrow transplantation].

Two patients after bone marrow transplantation (BMT) developed chronic progressive radiation myelopathy (CPRM). The factors contributing to development of CPRM at the low dose, which radiation doses given for enlarged regional lymph nodes prior to BMT ordinarily would be too low to induce CPRM, were discussed, and clinicoradiologic correlations in CPRM from onset through the stabilized state examined. The clinicoradiologic findings of two patients, who are a 26-year-old man with malignant lymphoma (autologous BMT) performed radiotherapy totaling 20 Gy for enlarged regional lymph nodes before BMT, and a 40-year old woman with chronic myeloid leukemia (allogenic BMT) done 18.9 Gy, were examined. The involved spinal cord segments were irradiated for lymph node enlargement prior to BMT, and all the clinicoradiologic findings were consistent with CPRM. We considered possible synergistic toxicity with high-dose busulfan accompanying BMT. Unlike the second case, the first patient had continued severe progression of CPRM, possibly because a higher dose of additional radiotherapy (30 Gy) was given for presumed spinal cord tumor involvement in that case than in the other (< 20 Gy). These cases demonstrate that BMT protocols carry a risk of potentiating the spinal cord toxicity of low-dose radiotherapy.

Adult↗

[Acute transformation of chronic myelomonocytic leukemia with t(1;3) (p36;q21) abnormality].

A 66-year-old man was given a peripheral blood test because of low grade fever. Leukocytosis was detected, and the blood and bone marrow findings were consistent with those of chronic myelomonocytic leukemia. Three months later the hematological findings were: WBC 58,800/microliter (19% blastoid cells, 22% monocytes), Hb 9.0 g/dl, and a platelet count of 116 x 10(4)/microliters. A bone marrow examination revealed the presence of 52.6% blastoid cells and dysmegakaryocytopoiesis, including micromegakaryocytes. Serum and urinary lysozyme levels were elevated. Karyotypic analysis detected t(1; 3) (p36;q21), but not major bcr/abl mRNA. The patient was given a diagnosis of acute transformation of chronic myelomonocytic leukemia. Despite treatment, he died about 3 months later. t(1;3) is occasionally observed in cases of myelodysplastic syndrome (MDS) and leukemia. Patients with t(1;3) often exhibit dysmegakaryocytopoiesis; furthermore, acute leukemia develops more readily in those who also have MDS. Cases of long-term survival are rare.

Aged↗

[Measurement of theophylline concentrations by AccuMeter--comparison with the EIA method].

Theophylline is widely used for treating patients with bronchial asthma. However, since the therapeutic concentration range is narrow, adverse reactions are frequent and often difficult to control, making monitoring of theophylline concentration mandatory for its efficient and safe use. In this study, we employed the AccMeter which allowed us to measure theophylline concentrations quickly and with ease, and compared it with EIA method. AccMeter is a kit which consists of two parts. One part consists of a chromatopaper with antitheophylline mouse monoclonal antibody fixed on it, on which a smaple is applied with enzyme-linked theophylline. The other part consists of a coloring solution. We used a part of arterial blood samples collected for gas analysis as trial samples. Both whole blood and plasma from 50 patients who did or did not receive theophlline were analysed. Plasma portions were also used for measurements by the EIA method. Results from all three measurements were almost identical, and showed good correlation. The time necessary for measurement using AccMeter was about 20 minutes. We consider this method to be useful for clinics due to its simplicity and ease of handling, and the accuracy of the results obtained.

Bronchodilator Agents↗

[Primary malignant lymphoma in the central nervous system treated with high dose methotrexate (MTX)-CHOP (M-CHOP)].

From December 1995 to July 1997, six patients with primary malignant lymphoma in the central nervous system were treated with 2 to 5 cycles of the M-CHOP regimen (methotrexate 3 g/m2 on day 1, cyclophosphamide 750 mg/m2 on day 1, doxorubicin 40 mg/m2 on day 1, vincristine 1.4 mg/m2 on day 1, and predonisolone 60 mg on day 1 to 14: folic acid was given 3 hours after methotrexate at 10 mg/m2 every 3 hours for 9 doses intravenously). Five patients achieved complete remission (CR) and one experienced partial remission (PR). Posttherapeutic studies were performed in all patients with an average follow-up period of 20.1 months (range 8.1-26.8 months) after confirming the diagnosis. There was no evidence of recurrence of the tumors or growth of residual tumors in any of the patients in this period. The major toxic effect was myelosupression with leukopenia. Alopecia was observed in all patients. No treatment-related deaths were observed. The M-CHOP regimen seems to be a promising treatment for primary malignant lymphoma in the central nervous system.

Adult↗

[Recent arguments in advanced gastric cancer treatment].

In advanced inoperable gastric cancer patients, survival was significantly prolonged for the group receiving antineoplastic treatment against only the best supportive care group by some randomized controlled studies. Greater prolongation of survival is expected from surgery in CR and PR cases because of the change from inoperable to operable. One problem is that the evaluation of response to the primary site is different between Japan and other countries. Outside of Japan, it is considered that barium contrast studies and routine endoscopy are not sufficient for tumor response assessment at the primary site. I think this is not true evaluation of the response to gastric cancer chemotherapy to exclude primary site assessment. We must generalize the Japanese criteria of gastric cancer chemotherapy throughout the world.

Antineoplastic Combined Chemotherapy Protocols↗

[A clinical evaluation of combination therapy with radiation, MCNU, carboplatin and IFN-beta or with radiation, MCNU, carboplatin, etoposide and IFN-beta for malignant gliomas].

In this study, we examined the clinical course and prognosis of 32 patients with malignant glioma (17 patients with anaplastic astrocytoma, 15 patients with glioblastoma) treated with the MIC regimen (radiation, MCNU, carboplatin and IFN-beta) or MICE regimen (radiation, MCNU, carboplatin, etoposide and IFN-beta). Ten patients were treated with the MIC regimen and 22 patients with the MICE regimen. The patients treated with the MIC and MICE regimens exhibited no significant difference in clinical background factors. The response rate was 50.0% among the 8 evaluable patients treated with the MIC regimen, and 40.0% among the 20 evaluable patients treated with the MICE regimen. The first- and second-year survival rates for the MIC regimen were 40.0% and 30.0%, and those for the MICE regimen were 68.2% and 36.4%. The overall first- and second-year survivals were 59.4% and 33.9%, respectively. The 50% survival time was 8.6 months for the MIC regimen, 14.9 months for the MICE regimen, and 13.4 months overall. There was no significant difference in response rate or survival period between the group treated with the MIC regimen and that treated with the MICE regimen. Age, histological grade of malignancy, radicality of surgery and total dose of irradiation did not affect length of survival. The only factors significantly related to length of survival were response to the induction therapy and performance of maintenance therapy. These results did not demonstrate the superiority of either the MIC or MICE regimen to other regimens previously reported for the treatment of glioma. In addition, etoposide was found not to improve the efficacy of this type of combined chemoradiation therapy.

Adolescent↗

[A case of giant advanced breast cancer responding remarkably to chemo-endocrine therapy chiefly with doxifluridine].

A 68-year-old woman presented with advanced ulcerative breast cancer of the precordium; edema of the face, cervix and bilateral upper extremities; dyspnea from carcinomatous pleurisy; and multiple bone metastases, which suggested a terminal state. Her general condition improved with symptomatic therapies; thus, doxifluridine (5'-DFUR) and an endocrine therapeutic drug were given to reduce the primary focus, eliminate the edemas and decrease the plural effusion. When the tumor markers increased again, CEFT therapy [cyclophosphamide (CPA), epirubicin (epi-ADM), 5-fluorouracil (5-FU) and tamoxifen (TAM)] was conducted. This resulted in no adverse drug reaction, further reduction of the primary focus, and extremely improved Performance status (PS). The patient was discharged on 5'-DFUR and TAM therapy, which resulted in scarring of the ulcer, normalization of tumor marker levels, disappearance of the pleural effusion, and a reduction of metastatic bone foci. The findings suggest 5'-DFUR and endocrine therapeutic drugs can have a favorable clinical effect without impacting QOL and should be employed in patients with advanced cancer and poor general condition.

Aged↗

Chemical, metabolic and immunological characterization of gangliosides of human glioma cells.

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.

Antibodies, Monoclonal↗

Symmetry breaking in Dictyostelium morphogenesis: evidence that a combination of cell cycle stage and positional information dictates cell fate.

The event that visibly breaks the symmetry of the Dictyostelium aggregate is the formation of a nipple-shaped tip at its apex, but there has been considerable debate as to the equivalence of cells entering development, particularly with regard to the effect of cell cycle position at the onset of starvation. We show that there is a strong correlation between cell cycle position at the time of starvation and the subsequent expression of a marker of tip cell differentiation. Cells starved in late-G2 phase selectively differentiate into tip cells. Previous evidence indicated that tip cells differentiate at the extreme periphery of the aggregate and then move to the apex. Taken in combination, these data suggest that cell cycle position at the onset of starvation affects differentiation fate by determining a cell's probable position within the aggregate, i.e., that both cell cycle and positional information are used to generate pattern.

Animals↗

Activation of serum response factor in the liver of Long-Evans Cinnamon (LEC) rat.

We have studied the DNA binding activities of transcription factors in the liver of Long-Evans Cinnamon (LEC) rats, an animal model of Wilson's disease. Owing to a genetic defect, this strain of rats accumulates excessive copper in the liver and develops severe hepatitis and hepatocellular carcinoma. We found that the DNA binding activity of the serum response factor (SRF) was higher in the liver of LEC rats (approximately 2-fold) than in that of Wistar rats. There was a close correlation between the intensity of the activity and the concentrations of copper in the nuclear protein. The DNA binding activity of Sp1, on the other hand, showed similar levels in both LEC and Wistar rats. SRF may play an important role in the development of hepatocellular carcinoma in LEC rats by mediating the proto-oncogene c-fos induction. We suggest that the copper in nuclear protein may be involved in the activation of SRF.

Animals↗

Comparison of the effects of selective endothelin ETA and ETB receptor antagonists in congestive heart failure.

OBJECTIVES: This study was designed 1) to determine the extent to which endogenous endothelin (ET) affects hemodynamic, hormonal and body fluid balance through ETA and ETB receptors in congestive heart failure (CHF); and 2) to assess the therapeutic benefits and adverse effects of ET receptor antagonists for ETA and ETB on cardiorenal and neurohormonal variables. BACKGROUND: ET has two receptors, ETA and ETB, both of which are distributed in various tissues and cells. In vascular beds, ETA receptors mediate vasoconstriction, whereas ETB receptors mediate vasorelaxation. However, ETB receptors also exist in smooth muscle and mediate vasoconstriction. METHODS: We administered either the ETA receptor antagonist FR139317 (FR [n = 8], 1 and 10 mg/kg body weight) or the ETB receptor antagonist RES-701-1 (RES [n = 8], 0.2 and 1.5 mg/kg) to dogs with CHF induced by rapid ventricular pacing. The effects of both antagonists on cardiorenal and hormonal functions were studied. RESULTS: FR decreased cardiac pressures and the plasma atrial natriuretic peptide (ANP) level and increased cardiac output (CO). Urinary flow rate and urinary sodium excretion increased in association with an increase in the glomerular filtration rate and renal plasma flow (RPF). In contrast, RES increased cardiac pressures and decreased CO. It also decreased the plasma aldosterone level and RPF. Neither antagonist affected plasma norepinephrine levels. CONCLUSIONS: Endogenous ETs increase cardiac pressures and the retention of body fluid through ETA receptors in CHF. The vasodilative action through ETB receptors is overall functionally more important than the constrictive action through ETB receptors. ETs may regulate the secretion of ANP and aldosterone. Our findings suggest that selective ETA receptor antagonists have potential therapeutic benefits affecting both hemodynamic variables and diuresis, whereas ETB receptor antagonists have adverse hemodynamic effects, with the possibility of preventing fluid retention through suppression of aldosterone secretion in dogs with CHF.

Analysis of Variance↗

Serotonin inhibits nitric oxide synthesis in rat vascular smooth muscle cells stimulated with interleukin-1.

We investigated the effects of serotonin (5-hydroxytryptamine; 5-HT) on nitric oxide (NO) synthesis in vascular smooth muscle cells. We measured the production of nitrite, a stable metabolite of NO, and the expression of inducible NO synthase protein in cultured rat vascular smooth muscle cells. Incubation of the cultures with interleukin-1beta (10 ng/ml) caused a significant increase in nitrite production. 5-HT inhibited nitrite production by interleukin-1beta -stimulated vascular smooth muscle cells in a concentration-dependent manner (10(-8)-10(-5) M). 5-HT-induced inhibition of nitrite production was accompanied by decreased inducible NO synthase protein accumulation in vascular smooth muscle cells. Addition of the 5-HT2 receptor antagonist ketanserin, but not the 5-HT1A receptor antagonist spiroxatrine, inhibited the effect of 5-HT. On the other hand, the 5-HT2 receptor agonist alpha-methyl-5-HT, but not the 5-HT1A receptor agonist (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin, decreased interleukin-1beta-induced nitrite production by vascular smooth muscle cells. 5-HT significantly increased protein kinase C activity in vascular smooth muscle cells, and the protein kinase C inhibitor calphostin C dose-dependently abolished the effect of 5-HT on nitrite production. After protein kinase C activity was functionally depleted by treatment of cells with phorbol 12-myristate 13-acetate for 24 h, the effect of 5-HT was abolished. These results indicate that 5-HT acts on 5-HT2 receptors and inhibits NO synthesis in interleukin-1beta-stimulated vascular smooth muscle cells at least partially through a protein kinase C-dependent pathway.

Animals↗

The V1/V2 region of human immunodeficiency virus type 1 modulates the sensitivity to neutralization by soluble CD4 and cellular tropism.

A primary isolate (KMT) of human immunodeficiency virus type 1 (HIV-1) resistant to recombinant soluble CD4 (rsCD4) was isolated from an HIV-1-infected individual and grown in a T lymphoid cell line. KMT isolate passaged on CEM cells (KMT/CEM) was still resistant to rsCD4. The V1/V2 and V3 regions of the viral envelope glycoprotein are thought to be involved in various biological phenotypes. To determine the exact envelope region of the KMT isolate responsible for sensitivity to rsCD4 and cellular tropism, we performed sequence analysis of KMT and KMT/CEM isolates. Sequence analysis of the KMT isolate showed that the sequence of the V3 region was relatively homogeneous, whereas a considerable heterogeneity of the V1/V2 region was noted. In contrast, the sequences of the V1 to V3 regions were homogeneous in KMT/CEM isolates. Analysis of NL4-3-based recombinant viruses with amplified sequences of the V1 to V3 regions from KMT and KMT/CEM isolates showed that the V1/V2 region modulated the sensitivity to rsCD4. A change in resistance to rsCD4 by the V1/V2 region was associated with the ability of the isolate to replicate in macrophages and efficiently replicate in T lymphoid cell lines. A change to an isolate sensitive to rsCD4 was associated with reduced replication efficiency in T lymphoid cell lines. Our results suggest that the V1/V2 region is involved in modulating the sensitivity to rsCD4, macrophage tropism, and replication efficiency in T lymphoid cell lines.

Amino Acid Sequence↗

Study of the action of human salivary alpha-amylase on 2-chloro-4-nitrophenyl alpha-maltotrioside in the presence of potassium thiocyanate.

The degradation mechanism of a synthetic substrate, 2-chloro-4-nitrophenyl alpha-maltotrioside (CNP-G3), by human salivary alpha-amylase (HSA) was investigated by kinetic and product analyses. It was observed that the enzyme attacked the various CNP-maltooligosaccharides (CNP-G3 to CNP-G6) releasing free CNP. Addition of 500 mM potassium thiocyanate (KSCN) was also found to greatly increase the rates of CNP-release. It was the fastest with CNP-G3, and, in the presence of KSCN, was almost comparable to that of degradation of maltopentaose (G5). On the other hand, addition of KSCN decreased the rate of cleavage between glucan-glucan bonds in maltopentaose. Product analysis showed that KSCN addition altered the cleavage distribution which occurred 100% at the bond between CNP and G3, and that product distribution of free CNP was largely dependent on substrate concentration. Formation of CNP-G6, a larger product than the original substrate CNP-G3, was found to be present in the digest at high concentrations of substrate and in the presence of KSCN. Based on these results, a degradation pathway for CNP-G3 involving transglycosylation besides direct hydrolysis is proposed. The increase of the CNP-release by the addition of KSCN would result from a corresponding increase in the interaction between the CNP moiety and the corresponding subsite near the catalytic site, as well as the enhancement of the catalytic efficiency.

Chromatography, High Pressure Liquid↗