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Biomedical subjects

H Ikeda

Publications and source records attributed to H Ikeda.

At least 271 records · Page 15Linked to original sources

A new technique for transurethral resection of superficial bladder tumor in 1 piece.

PURPOSE: We developed a new transurethral resection technique that not only removes the entire tumor, but also the surrounding mucosa and underlying stroma with superficial proper muscle in 1 piece to determine accurately the depth of invasion and infiltration pattern of superficial bladder cancer. MATERIALS AND METHODS: A short curved needle electrode is used to make a circular incision around and level incisions underneath the tumor, and for tumor retrieval. RESULTS: Tissue sections of the cut surface crossing the tumor center revealed accurate histology regarding the growth pattern and depth of invasion. No perforation, uncontrollable bleeding or other serious complications occurred. CONCLUSIONS: More accurate histological diagnosis regarding the growth pattern and depth of lamina propria invasion was possible with removal of the tumor and surrounding material in 1 piece compared to conventional transurethral resection.

Electrodes↗

[Mechanisms of thiazolidinedione derivatives for hypoglycemic and insulin sensitizing effects].

Ciglitazone was the first insulin sensitizer with a thiazolidinedione structure to reduce insulin resistance and hyperglycemia and many thiazolidinedione derivatives (TZDs) have since been reported as insulin sensitizers. Pioglitazone is reported to lower blood glucose through reductions in both hepatic and peripheral insulin resistance. Regarding the molecular mechanism, pioglitazone was first reported to increase the tyrosine kinase activity of the insulin receptor and then TZDs were reported to increase the insulin signal transduction. TNF-alpha causes insulin resistance through inhibition of the insulin signal transduction and TZDs have been shown to reduce insulin resistance by the suppression of the TNF-alpha gene expression. In addition, TZDs are specific agonists of PPAR gamma and the hypoglycemic effect of TZDs has been shown to involve PPAR gamma among the PPARs. Based on these observations, the molecular mechanisms of TZDs are discussed.

Animals↗

[Radiation therapy for malignant lymphoma].

For the treatment of malignant lymphoma(ML), it is important to recognize its clinical features. Recently, the role of radiation therapy(RT) has been reconsidered in the treatment of ML because of the effectiveness of combined modality treatment (CMT) for early-stage aggressive non-Hodgkin's lymphoma(NHL). Recent data suggest that adjuvant radiotherapy to the bulky site in advanced-stage aggressive NHL may significantly improve the relapse-free survival and overall survival. On the other hand, in the treatment of early-stage Hodgkin's disease(HD), meta-analysis data showed no apparent survival benefit from CMT or extended RT compared with RT alone. So in the initial treatment of early-stage HD, RT alone with adequate field should be recommended. Low-grade mucosa-associated lymphoid tissue(MALT) lymphoma is considered to be an additional indication for the use of RT because it is very sensitive to radiation and potentially curable with RT.

Antineoplastic Combined Chemotherapy Protocols↗

[A case of a pituitary mass in association with sarcoidosis].

We report a case of a pituitary mass associated with sarcoidosis. Natural regression of the mass was demonstrated after the replacement of corticosteroid hormone. A seventy-one-year old man presented with blurred vision and general fatigability, and admitted to our hospital. He was diagnosed to have ophthalmic and pulmonary sarcoidosis. Two months later, he consulted our hospital again, with complaints of fatigability and vomiting. Laboratory data showed hyponatremia, and CT scan revealed a suprasellar mass. He had no neurological deficits. Diabetes insipidus was not observed. Magnetic resonance image showed a heterogeneously enhanced intrasellar and suprasellar dumbbell shaped mass and thickening of the pituitary stalk. Hormonal examination revealed corticosteroid insufficiency and hypothyroidism, possibly caused by the pituitary mass. Replacement of corticosteroid hormone significantly improved his fatigability. Two months later, follow-up MRI showed regression of the pituitary mass. Based on the clinical and radiological findings, pituitary mass was strongly suggested to be caused by sarcoidosis. We recommend prompt steroid treatment for such a pituitary mass and strict follow-up MRI study.

Aged↗

[A pilot study of irinotecan hydrochloride for metastatic breast cancer--efficacy as a salvage therapy].

From April 1996 through 1998, we treated twelve metastatic breast cancer patients with CPT-11 100 mg/m2 given on day 1, 8, and 15. All patients had received prior chemotherapy including anthracycline, and also another schedule such as MMC-VDS or HDMTX-5-FU. CPT-11 was well tolerated. One CR, two PR, and two long NC were achieved. Grade 3 leukocytopenia occurred in 2 patients. Grade 1 diarrhea occurred in 3 patients. According to the Kaplan-Meier method, the 50% survival was 354 days. In spite of intense prior chemotherapy, the treatment results with CPT-11 were satisfactory for anthracycline resistant metastatic breast cancer.

Adult↗

[Prognosis of hypertrophic and dilated cardiomyopathy].

Hypertrophic and dilated cardiomyopathies are a heterogeneous disease, both clinically and genetically. Hypertrophic cardiomyopathy(HCM) is important causes of sudden cardiac death and death from congestive heart failure, although HCM has a relatively benign prognosis. The prognosis of dilated cardiomyopathy(DCM) has improved due to advances in earlier diagnosis and therapy, however, sudden cardiac death and death from congestive heart failure still occur in DCM. Accordingly, it is of importance to know possible risk factors on risk stratification for a high-risk group in HCM and DCM. Possible risk factors may contribute to the construction of therapeutic strategies for the prevention of sudden cardiac death or death from congestive heart failure in patients with HCM and DCM.

Adrenergic beta-Antagonists↗

Lipopolysaccharide-triggered desensitization of TNF-alpha mRNA expression involves lack of phosphorylation of IkappaBalpha in a murine macrophage-like cell line, P388D1.

Activation of nuclear factor kappaB (NF-kappaB) is thought to be required for cytokine production by lipopolysaccharide (LPS)-responsive cells. Here, we investigated the contribution of NF-kappaB in preventing LPS-induced transcription of the tumor necrosis factor alpha (TNF-alpha) gene in a murine macrophage cell line, P388D1, when tolerance was induced in the cells with a short exposure to a higher dose of LPS. Electrophoretic mobility shift assays with the kappaB elements of the murine TNF-alpha promoter and enhancer revealed that nuclear mobilization of heterodimers of p65/p50, c-rel/p50 and p65/c-rel, and homodimers of p65 was markedly reduced in LPS-tolerant cells, whereas that of p50 homodimers was only slightly increased. Western blot analysis showed that the phosphorylation of Ser32 on IkappaBalpha and its transient degradation did not occur in LPS-tolerant cells. These results thus suggest that desensitization of TNF-alpha gene expression in this LPS-tolerant state is closely associated with down-regulation of transactivating NF-kappaB and may involve a defect in the LPS-induced IkappaBalpha kinase pathway.

Animals↗

[Three cases of measles-associated interstitial pneumonia].

It has been reported that measles-associated pneumonia is easily complicated with fatal respiratory failure. During the 6 months from January to June 1998, we treated three young patients with measles-associated pneumonia who had previously been healthy. Their chest X-ray and CT examinations revealed mainly interstitial and partially alveolar pneumonia surrounding extensive areas of bronchiolitis. In one patient, respiratory failure was present, and arterial blood gas analysis showed severe hypoxemia. Therefore, this patient was treated with a mechanical ventilator, which dramatically improved the condition. The other two patients received steroid-pulse therapy and improved rapidly. We believed that in measles-associated pneumonia, steroid pulse therapy is to be recommended for the severely ill patient. According to a report by the Japanese Ministry of Health and Welfare, measles-like disease was widespread in Japan in 1991 and occasionally encountered in 1996. But in Yamanashi Prefecture, the disease was prevalent in 1991, 1994 and 1998. The number of patients in our hospital had reflected the prevalence in the prefecture. It is suggested that the measles is a disease of regional prevalence.

Adult↗

Elucidation of the HIV-1 virucidal mechanism of methylene blue photosensitization and the effect on primary isolates.

The antiviral activity for primary isolates of human immunodeficiency virus (HIV) type 1 of a combination of methylene blue and light irradiation was investigated, in comparison with their virucidal effects on laboratory-adapted HIV-1. The antiviral mechanism was evaluated in terms of reverse transcriptase activity and viral RNA in the same viral stock. Despite a marked reduction in RNA (>3.07 Log(10)) and infectivity (6.10 Log(10)) under conditions of 1 microM methylene blue and 5 J/cm(2) irradiation when HIV-1(HTLV-IIIB) as a representative HIV-1 was employed, relatively little degradation of the viral envelope (0.20 Log(10)) and reverse transcriptase activity (1.52 Log(10)) was observed. Because no difference in the reduction of infectivity was found between primary isolates and laboratory-adapted HIV-1 (including HIV-2(ROD)), the antiviral mechanism of methylene blue photosensitization may be similar for all types of HIVs. Methylene blue photosensitization seems to deprive HIVs of infectivity, mainly due to RNA damage, and weak structural and functional damage of viral proteins.

Adaptation, Physiological↗

[Intra-arterial infusion chemotherapy in combination with microwave hyperthermia for cancer of head of pancreas and liver metastasis--a case of 16 years survival].

Our experience of arterial infusion chemotherapy combined with regional hyperthermia in the treatment of non-resectable pancreatic cancer was presented. A patient with cancer in the pancreatic head with accompanying extensive metastasis in both hepatic lobes was treated by sub selective aortic infusion of 5-FU and MMC with microwave hyperthermia. Both the cancer in the pancreatic head and the liver metastasis showed complete remission for 16 years.

Antineoplastic Combined Chemotherapy Protocols↗

Human anti-Dia monoclonal antibodies for mass screening.

The use of monoclonal antibodies (mabs) to blood group antigens is constantly increasing for routine typing. Two heterohybridoma cell lines, HMR15 and HMR22, were established by Epstein-Barr virus transformation of peripheral blood lymphocytes from a blood donor with anti-Dia. HMR15 mab directly agglutinated Di(a+) red cells, and HMR22 mab agglutinated Di(a+) red cells exclusively by the indirect antiglobulin test. Reactivities of both HMR15 and HMR22 mabs were specific for Dia and had good correlation with the reactivity of a commercial, polyclonal antiserum. The binding of monoclonal antibodies to antigen-positive red cells was mutually blocked by each other as well as by polyclonal anti-Dia. Immunoprecipitates by HMR22 mab with a Di(a+) preparation showed a 120 kDa band that was stained by anti-band 3. Dia typing of 2427 blood donors with the mabs and polyclonal typing serum detected 244 Di(a+) individuals (10.1%). No discrepancy was observed between the mabs and the polyclonal antiserum. HMR15 and HMR22 mabs are useful Dia typing reagents and can substitute for commercial antiserum.

Journal Article↗

The assembly of beta-methylene-TAD, a metabolically stable analogue of the antitumor agent TAD, by the stepwise esterification of monodeprotected methylenebis-(phosphonate) benzyl esters under Mitsunobu conditions.

Synthesis of the metabolically stable analogue of thiazole-4-carboxamide adenine dinucleotide (beta-methylene-TAD) was achieved via the sequential monodeprotection of tetrabenzyl methylenebis(phosphonate) after two rounds of Mitsunobu esterifications with the corresponding nucleoside components, tiazofurin and adenosine.

Adenosine Diphosphate↗

Identification of natural antigenic peptides of a human gastric signet ring cell carcinoma recognized by HLA-A31-restricted cytotoxic T lymphocytes.

Peptides of human melanomas recognized by CD8+ CTLs have been identified, but the nature of those of nonmelanoma tumors remains to be elucidated. Previously, we established a gastric signet ring cell carcinoma HST-2 and HLA-A31 (A*31012)-restricted autologous CTL clone, TcHST-2. In the present study, we determined the natural antigenic peptides of HST-2 cells. The purified preparation of acid-extracted Ags was submitted to the peptide sequencer, and one peptide, designated F4.2 (Tyr-Ser-Trp-Met-Asp-Ile-Ser-Cys-Trp-Ile), appeared to be immunogenic. To confirm the antigenicity of F4.2 further, we constructed an expression minigene vector (pF4.2ss) coding adenovirus E3, a 19-kDa protein signal sequence plus F4.2. An introduction of pF4.2ss minigene to HST-2 and HLA-A31(+) allogeneic tumor cells clearly enhanced and induced the TcHST-2 reactivity, respectively. Furthermore, when synthetic peptides of F4.2 C-terminal-deleted peptides were pulsed to HST-2 cells, F4.2-9 (nonamers), but not F4.2-8 or F4.2-7 (octamer or heptamer, respectively), enhanced the reactivity of TcHST-2, suggesting that the N-terminal ninth Trp might be a T cell epitope. This was confirmed by lack of antigenicity when using synthetic substituted peptides as well as minigenes coding F4.2 variant peptides with Ala or Arg at the ninth position of F4.2. Meanwhile, it was indicated that the sixth position Ile was critically important for the binding to HLA-A31 molecules. Thus, our data indicate that F4.2 may work as an HLA-A31-restricted natural antigenic peptide recognized by CTLs.

Amino Acid Sequence↗

Organization of the biosynthetic gene cluster for the polyketide anthelmintic macrolide avermectin in Streptomyces avermitilis.

Analysis of the gene cluster from Streptomyces avermitilis that governs the biosynthesis of the polyketide anthelmintic avermectin revealed that it contains four large ORFs encoding giant multifunctional polypeptides of the avermectin polyketide synthase (AVES 1, AVES 2, AVES 3, and AVES 4). These clustered polyketide synthase genes responsible for avermectin biosynthesis together encode 12 homologous sets of enzyme activities (modules), each catalyzing a specific round of polyketide chain elongation. The clustered genes encoding polyketide synthase are organized as two sets of six modular repeats, aveA1-aveA2 and aveA3-aveA4, which are convergently transcribed. The total of 55 constituent active sites makes this the most complex multifunctional enzyme system identified to date. The sequenced DNA region contains 14 additional ORFs, some of which encode polypeptides governing other key steps in avermectin biosynthesis. Between the two sets of polyketide synthase genes lie two genes involved in postpolyketide modification, one of which encodes cynthochrome P450 hydroxylase that probably catalyzes furan ring formation at C6 to C8a. Immediately right of the large polyketide synthase genes is a set of genes involved in oleandrose biosynthesis and its transglycosylation to polyketide-derived aglycons. This cluster includes nine genes, but one is not functional in the biosynthesis of avermectin. On the left side of polyketide synthase genes, two ORFs encoding methyltransferase and nonpolyketide synthase ketoreductase involved in postpolyketide modification are located to the left of the polyketide synthase genes, and an adjacent gene encodes a regulatory function that may be involved in activation of the transcription of avermectin biosynthetic genes.

Anthelmintics↗

High frequency of inactivation of the imprinted H19 gene in "sporadic" hepatoblastoma.

Embryonal tumors such as Wilms' tumor (WT), embryonal rhabdomyosarcoma (eRMS) and hepatoblastoma have been thought to have a common pathogenetic mechanism. H19 was found to be inactivated in WT and eRMS either by loss of heterozygosity or by hypermethylation of the maternal allele. We show here that the expression of the H19 gene is inactivated by maternal allelic loss or hypermethylation in 7 out of 8 "sporadic" hepatoblastomas. Furthermore, we analyzed expression of the IGF2 gene. Loss of imprinting of the IGF2 gene was detected and linked to inactivation of the H19 gene in 2 hepatoblastomas. However, 2 sporadic cases demonstrated monoallelic expression of the IGF2 gene with inactivation of the H19 gene. Our results suggest that H19 may play a role as a common imprinted tumor suppressor gene in "sporadic" hepatoblastomas but may at times work independently of IGF2 expression.

Child↗