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Biomedical subjects

Y Kagami

Publications and source records attributed to Y Kagami.

At least 19 recordsLinked to original sources

Neuroprotective effect of 5-HT3 receptor antagonist on ischemia-induced decrease in CA1 field potential in rat hippocampal slices.

The effect of 5-HT3 receptor agonists and antagonists on the hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 field potential elicited by stimulation of Schaffer collaterals was investigated using rat hippocampal slices. Treatment with the 5-HT3 receptor agonist, 2-methyl-5-HT (1-10 microM), exacerbated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5-HT3 receptor antagonist, Y-25130 (0.1-100 microM), or the 5-HT2 receptor antagonist, ketanserin (10, 100 microM), produced dose-dependent neuroprotection against the ischemia-induced decrease. However, in normal non-ischemic solution these treatments did not significantly change the CA1 field potential. The protective action of Y-25130 was blocked by co-treatment with 2-methyl-5-HT. The magnitude of protection in the Y-25130-treated group (EC50, 1.8 microM) was about 20 times greater than that in the ketanserin-treated group (EC50, 33 microM). The present study demonstrated that stimulation of 5-HT3 receptors plays a detrimental role in the development of ischemic damage, whereas blockade of the 5-HT3 receptor plays a neuroprotective role in ischemic damage, suggesting a facilitatory role of 5-HT neurons in ischemia-induced neuronal deficits.

5,7-Dihydroxytryptamine

[Prospective randomized trials comparing hyperfractionated radiotherapy with conventional radiotherapy in stage III non-small cell lung cancer].

From September 1987 to August 1990, 36 patients with stage III non-small cell lung cancer were randomly assigned to 65 Gy in 26 fractions of 2.5 Gy each (conventional radiotherapy) or 71.5 Gy in 52 fractions of 1.375 Gy given twice a day (hyperfractionated radiotherapy). The overall time for both groups was 6.5 weeks. The groups were similar in terms of age, performance status, previous chemotherapy, stage IIIA and IIIB, and histopathology. The rate of complete response was 44.4% for hyperfractionation, and 16.7% for conventional fractionation. Overall survival rates at 24 months and 36 months were 50.0% and 21.8% for hyperfractionation, and 31.3% and 0% for conventional fractionation. Fever due to radiation pneumonitis occurred in seven of 18 patients with hyperfractionation (38.9%) and four patients with conventional fractionation (22.2%). No severe late toxicity has been observed in either group. We conclude that hyperfractionated radiotherapy in non-small cell lung cancer may improve survival without increasing severe toxicity.

Adult

Intracavitary brachytherapy combined with external-beam irradiation for squamous cell carcinoma of the thoracic esophagus.

During the 15 year period from 1974 to 1988, 277 patients with previously untreated, histologically confirmed, squamous cell carcinoma of the thoracic esophagus were treated with the Time Dose and Fractionation (TDF) factor of more than 99. Of these, 161 patients were treated with external beam irradiation combined with intracavitary brachytherapy. Intracavitary brachytherapy was done for all patients for whom insertion of an outer applicator 1 cm in diameter was possible and for whom a relatively good performance status was seen at completion of external beam irradiation. Except for mild radiation-induced esophagitis, no acute radiation injuries were noted. The early clinical effect of radiation upon the esophageal lesion was determined by esophagography and esophagoscopy, approximately 1 month after the combined radiotherapy; a complete response was observed in 86 (53.4%) of the 161 patients. Furthermore, after a 5 year follow-up, local control of esophageal cancer was found to have been successful in 51 (31.7%) of the 161 patients. The highest rate of local control was associated with the following criteria: Stage I, T1, tumor length less than 5 cm, and superficial or tumorous type of tumor. The 5-year actuarial survival rates were 43.3% for Stage I, 21.1% for Stage II, and 0% for both Stages III and IV. Benign radiation-induced esophageal ulcerations or strictures did develop in five of the long-term survivors, suggesting that the dosage is close to the maximal tolerance of the esophagus. We recommend that 1500-2000 cGy in two or three fractions is the optimal dosage for intracavitary radiation of the esophageal mucosa after external irradiation of 5500 cGy in 22 fractions for 5.5 weeks or 6000 cGy in 30 fractions for 6 weeks. We believe that intracavitary treatment of esophageal carcinoma is a highly effective and a safe therapeutic modality, not only as a palliative therapy, but also as a radical treatment for patients in Stages I and II.

Aged

Male-specific metabolism of simvastatin by rat liver microsomes.

Simvastatin was more effectively metabolized by the liver microsomes of male rats than females. The sex difference appeared in the composition of the metabolites. Two male-specific metabolites were identified by NMR and mass spectrometry as 3''-hydroxy and 3',3''-dihydroxy-delta 4',5' derivatives of simvastatin.

Animals

[A case of RAEB-t treated by G-CSF showing complete remission after MST-16 treatment for subsequent reversible leukemia].

A seventy-five-year-old female with general fatigue, high fever and anemia was admitted. Her chest X-ray film revealed pneumonia. She was diagnosed as RAEB-t with the normal karyotype by peripheral blood film and bone marrow aspiration; 125 micrograms/ml of G-CSF was administered s.c. daily in order to increase neutrophil count because of the prolongation of pneumonia. Her blast cells in both peripheral blood and bone marrow showed a remarkable increase by G-CSF. After the cessation of G-CSF administration, blast cells decreased rapidly, and neutrophil count in the peripheral blood increased. Her pneumonia was then cured. After 5 months of stable hematological state, 60% of her bone marrow cells became occupied by blast cells again. So 2 consecutive courses of 14 days p.o. administration of 1,200 mg MST-16/day were tried. Three months after the first MST-16 trial, her bone marrow showed complete remission (CR) which lasted about 4 months. But she died of sepsis after the first relapse. Her bone marrow in CR still revealed several features of dyspoiesis.

Acute Disease

Cytogenetic and clonal culture evaluation after response to low dose Ara-C in myelodysplastic syndromes.

Cytogenetic and bone marrow culture studies were performed sequentially in 13 patients with myelodysplastic syndromes (MDS) who responded to low dose cytosine arabinoside (Ara-C) treatment (complete in nine and partial in four patients). Of nine patients with initial clonal karyotypic abnormalities, six recovered a normal karyotype after attaining a response to treatment, but the other three patients retained partial or total karyotypic abnormalities. A new clonal karyotypic abnormality appeared after treatment in one patient. Eight patients showed normal colony growth of both granulocyte-macrophage colony-forming units and erythroid burst-forming units after treatment, but five were still defective. There was a clear difference in the duration of response to treatment between these two groups. Consolidation treatment was not effective in patients with persistent karyotypic abnormalities or defective colony formation. Although the number of patients studied is small, these results suggest that hemopoiesis in patients with MDS following a response to treatment with low dose Ara-C is heterogeneous. Consolidation chemotherapy is recommended to ensure and prolong the response in patients showing normalization of both cytogenetic and bone marrow culture results.

Adolescent

Interleukin 4 and gamma-interferon may play a role in the histopathogenesis of peripheral T-cell lymphoma.

The first demonstration of cytokine expression in T-cell lymphoma by immunohistochemical methods is reported. Lymph node biopsy specimens were obtained from 18 patients with peripheral T-cell lymphoma. Interleukin 4 (IL-4) and gamma-interferon were each detected in 7 lymph nodes. Lymph node specimens diagnosed as angioimmunoblastic T-cell lymphoma and angiocentric lymphoma having distinctive histopathological features expressed IL-4 more frequently than other T-cell lymphomas, and all 7 patients expressing IL-4 had hypergammaglobulinemia. Lymph nodes with gamma-interferon expression showed an increase in histiocytes and/or epithelioid cells. Thus, IL-4 may play an important role in the development of hypergammaglobulinemia as well as in the growth and histopathogenesis of T-cell lymphoma, and gamma-interferon may be responsible for the development of Lennert's lesion.

Antibodies

Terminal differentiation of human erythroleukemia cell line K562 induced by aphidicolin.

To analyze the relationship between differentiation and DNA replication, the effect of aphidicolin, a specific inhibitor for DNA polymerase alpha, was measured with respect to erythroid differentiation and activities of DNA polymerases alpha, beta, and gamma. Five micromolar aphidicolin completely blocked the growth of K562 cells and caused 80% of cells to become hemoglobin positive after 5 days exposure. The cessation of K562 cell growth induced by aphidicolin was irreversible, whereas the inhibition of HeLa cell growth was completely reversible. The enzyme activity of DNA polymerase alpha of K562 cells showed a 50-110% increase with aphidicolin treatment as compared to control K562 cells; activities of DNA polymerases beta and gamma were not affected. These features sharply contrasted with the erythroid induction of the same cells by hemin, where cell growth was not suppressed and DNA polymerase alpha was not increased but rather decreased. The enzyme activity of DNA polymerase alpha remained high even after removal of aphidicolin from the culture medium. These results suggest that treatment with aphidicolin might induce an accumulation of protein factors for replication and/or differentiation, causing rapid cell differentiation of cells without cell division.

Antineoplastic Agents

Molecular cloning and characterization of a cDNA for a novel phorbol-12-myristate-13-acetate-responsive gene that is highly expressed in an adult T-cell leukemia cell line.

To identify gene products that might be involved in leukemogenesis of adult T-cell leukemia (ATL), we constructed a cDNA library from an ATL tumor cell line named IKD. By differential plaque hybridization using [32P]cDNAs of poly(A)+ RNA from IKD cells and a human T-lymphotropic virus type I-infected T-cell line (C91/PL) as probes and RNA blot analysis, we obtained a single cDNA clone of a gene that is highly expressed in IKD cells. Expression of this gene was also detected in fresh peripheral blood mononuclear cells of several ATL patients but not in those of healthy donors. Sequence analysis showed that the cDNA was that of a previously undescribed gene. On structural analysis of the cDNA (1,897 base pairs), a short open reading frame encoding a polypeptide of 54 amino acid residues was found. Exposure of human peripheral blood mononuclear cells, a T-cell lymphoma cell line (Jurkat), and quiescent human embryonic lung cells to phorbol-12-myristate-13-acetate resulted in rapid, transient expression of 2.0-kilobase mRNA of this gene. This induction of the gene was not inhibited by an inhibitor of protein synthesis, cycloheximide. From these findings, we suggest that this gene, named APR, is a member of the cellular immediate-early-response genes.

Amino Acid Sequence

[Chronic cytopenia associated with T8 lymphocytosis successfully treated with glucocorticoids].

We reported a prednisolone effective case of T 8 lymphocytosis. The patient was 83 years old male, who had suffered from hypoplastic anemia for more than 5 years before he admitted to our hospital. His blood picture was peculiar because adding to granulocytopenia, CD8 (+) large granular lymphocytes were dominant among his lymphocytes. A few days after administration of bolus methylprednisolone, prominent reticulocytosis and rapid improvement of anemia occurred and the latter continued for more than 1 year. We performed in vitro study on the mechanism of his cytopenias. The result of Southern blot analysis showed that his blood lymphocytes had a unique rearranged pattern of T cell receptor beta chain gene. Mononuclear cells had an inhibitory effect on autologous and allogenic CFU-E colony formation of bone marrow cells. These facts suggest that colony proliferating CD8 (+) lymphocytes had an inhibitory effect on erythropoiesis in vivo, and prednisolone blocked this inhibitory pathway in this patient.

Aged

[Clinical evaluation of cefbuperazone in severe infections complicated with hematological disorders].

The efficacy and the safety of an antibiotic in cephamycin group, cefbuperazone (CBPZ), were investigated in 93 patients with severe infections complicated with hematological disorders. The efficacy evaluation was made in 85 cases with underlying hematological disorders including 49 cases (57.6%) of leukemia and 18 cases (21.2%) of malignant lymphoma. The overall efficacy rate was 50.6% of the 85 evaluable cases. The clinical efficacy rate for sepsis and suspected sepsis was 53.4%. The most frequently used group of antibiotics for combination therapy was aminoglycosides in 37 cases, in which an efficacy rate of 62.2%, a higher rate than the efficacy rate of 48.5% for all the combination therapy cases, was obtained. In 16 cases in which penicillins were used as combination drug, the efficacy rate obtained was low, 31.3%. Efficacy rates obtained for cases with different neutrophil counts at the start of therapies were as follows: 52.2% in 23 cases with neutrophil counts below 100/mm3, 46.2% in 13 cases with neutrophil counts between 100 and 499/mm3 and 51.3% in 39 cases with neutrophil counts equal to or above 500/mm3, thus no significant differences in efficacy rates were observed for patients with different neutrophil counts. These results appear to suggest that CBPZ, alone or in combination with other antibiotic such as aminoglycosides, may be quite useful in the treatment of severe infections in patients with hematological disorders.

Adolescent

The AMeX method: a multipurpose tissue-processing and paraffin-embedding method. II. Extraction of spooled DNA and its application to Southern blot hybridization analysis.

In our previous report, we described a new fixation and paraffin-embedding method (the AMeX method) that preserves many of the antigens that are normally destroyed by routine formalin fixation. The current study was conducted to examine the preservation of high-molecular-weight DNA in tissues processed by this method. DNA was extracted from AMeX-processed tissue sections after deparaffinization by the same method as that used to extract DNA from fresh tissues. The total amounts of DNA extracted from 10 mg each in wet weight of AMeX-processed and fresh mouse liver tissues were identical. In tissues of malignant lymphoma, the total amount of spooled DNA extracted from 50 sections, each 20 microns thick, was about 8 micrograms/mm2. The electrophoretic pattern of DNA digested with restriction endonucleases on agarose gel from AMeX-processed tissue sections did not differ from that of fresh materials. Southern blot hybridization analysis also revealed that the mobility of specific DNA fragments was identical for AMeX-processed and fresh tissues. The AMeX method was thus proved to be a versatile multipurpose tissue-processing procedure, which is expected to provide important information regarding the correlation between morphology, phenotypic expression, and gene alteration.

Blotting, Southern

[Treatment of squamous cell carcinoma of the head and neck with multi-drug chemotherapy and radiotherapy].

Multi-drug chemotherapy containing cisplatin has been reported to be one of the most active chemotherapy regimens in advanced or recurrent head and neck squamous cell carcinoma. In this study, the current status of clinical investigation of combination chemotherapies is reviewed. And our data are presented in head and neck cancer with multi-drug chemotherapy containing cisplatin. Thirty-five patients of stage 3-4 and 70 patients with recurrent and/or metastatic head and neck squamous cell carcinoma were treated by multi-drug chemotherapy containing cisplatin, and radiotherapy and/or operation. The overall response rate was 71.4%, with 17.1% complete remission in previously untreated, locally advanced patients and 31.4% in recurrent or metastatic patients. Problems of chemotherapy combined with radiotherapy and future direction of clinical study in locally advanced or recurrent head and neck cancer are discussed.

Antineoplastic Combined Chemotherapy Protocols

[Radiotherapy and chemotherapy of esophageal cancer].

Radiotherapy for esophageal cancer is an available modality as well as surgery. Since radiotherapy for esophageal cancer is generally used for those patients with inoperable extensive disease, radiotherapy alone is unsatisfactory. New methods of radiotherapy are intracavitary treatment, hyperfractionation etc. Combination chemotherapy, especially including CDDP, seems to be more effective than single agents. Radiotherapy combined with chemotherapy is used by many investigators in an attempt to improve both local control and the cure rate of esophageal cancer.

Antineoplastic Combined Chemotherapy Protocols

[Antiemetic efficacy of betamethasone versus betamethasone combined with metoclopramide in cisplatin-treated cancer patients].

This study was designed to compare the antiemetic effect of betamethasone alone with that of betamethasone combined with metoclopramide. Forty-seven patients on chemotherapeutic regimens including cisplatin were entered into this study. Betamethasone was given in 4 doses of 20 mg/body at 30 minutes before and at 2.5 and 8 hours after cisplatin. Metoclopramide was given in 4 doses of 1mg/kg on the same schedule. Within 24 hours after the administration of cisplatin, no vomiting was observed in 42.9% of the patients treated with betamethasone alone and in 76.9% with betamethasone and metoclopramide. Betamethasone combined with metoclopramide was superior to betamethasone alone for the antiemetic effect in cisplatin-treated patients.

Adult

Concurrent adult T-cell leukemia and acute myeloblastic leukemia.

A 49-year-old man developed adult T-cell leukemia (ATL) and acute myeloblastic leukemia (AML) at the same time. Using Southern blotting analysis, the leukemic cells of the ATL were found to contain the human T-cell leukemia virus type I (HTLV-I) proviral genome, whereas those of the AML did not, indicating the HTLV-I not to be associated with the AML oncogenesis. At the initial presentation, the serum anti-HTLV-I antibody was judged on screening by a routine particle-agglutination (PA) test and an indirect immunofluorescence assay (IF) to be negative. By Western blotting analysis, however, the serum was proved to be positive for anti-HTLV-I antibody. These results indicate that a routine PA-test and an IF may show false negative reactions on very rare occasions of low antibody titer. This is the first report of a coincidence of ATL with another type of leukemia.

Antibodies, Viral