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H Kanno

Publications and source records attributed to H Kanno.

At least 19 recordsLinked to original sources
PubMed2000

In vivo gene gun-mediated DNA delivery into rodent brain tissue.

Various types of gene transfer into live tissues have been tried. However, in vivo gene transfer into brain tissue or neuronal cells without virus vector has required a great effort. Particle-mediated gene transfer into live brain tissue was thought to be impossible because of its fragility and the mechanical problem of a previous type of gene gun. In addition, particle-mediated DNA transfer into monolayer-cultured cells without mechanical damage has been difficult. We successfully transferred DNA into rodent live brain tissue and also into monolayer-cultured cells without mechanical damage by using a new type of gene gun and also confirmed gene expression in the brain. This new method represents another variation of gene transfer into the brain.

Animals↗
PubMed2000

Germ-line mutation analysis in patients with von Hippel-Lindau disease in Japan: an extended study of 77 families.

We have previously reported on the analysis of germ-line mutations in Japanese von Hippel-Lindau disease (VHL) patients and found mutations in 26 families. We have now extended these studies to include an additional 41 VHL families. Germ-line mutation of the VHL gene was screened by DNA-SSCP, direct sequencing, and Southern blot analysis. To summarize all of the data we have studied in this and our previous report, germ-line mutations have been detected in 55 of 77 (73%) (type 1: 41/62 (66%) and type 2: 14/15 (93%)) families. We found similarities in the nature of germ-line mutations including mutational incidence, location, and DNA substitution patterns between Japanese and Western VHL. These similarities may reflect the predominance of endogenous mutational processes. We also found several interesting characteristics in Japanese VHL. Twenty of 41 (49%) intragenic mutations were unique and not reported in the Western VHL. Four mutations (Arg113Stop, Gln132Stop, Leu158Val, and Cys162Tyr) previously characterized as type 1 mutations were identified in the type 2 (with pheochromocytoma) Japanese families. Genotype-phenotype correlation study suggested non-missense mutations predicted to result in the loss of VHL function were associated with the occurrence of renal cell carcinoma, as in sporadic tumors. Our data add to the diversity of VHL germ-line mutations and provide a better understanding of VHL disease in terms of both clinical management and molecular pathogenesis.

Genotype↗
PubMed2000

Microsatellite instability and k-ras, p53 mutations in thyroid lymphoma.

Patho-epidemiological studies showed that thyroid lymphoma (TL) arises in inflammatory lesions of chronic lymphocytic thyroiditis (CLTH). Replication error (RER) is found in inflammatory lesions and associated cancer, suggesting that chronic inflammation could be a risk factor for neoplastic development through causing RER. To clarify whether RER is involved in the pathogenesis of TL, we examined the microsatellite instability (MSI) in 9 cases with CLTH and 19 with TL, including 10 diffuse large B-cell lymphoma (DLBL), 4 follicle center cell lymphoma, 3 marginal zone B-cell lymphoma of extranodal (MALT) type, and 2 lymphoplasmacytic type. Sixteen distinct microsatellite repeats were analyzed. Mutations of p53 and k-ras genes were also examined. When alterations at 2 or more microsatellite loci were judged as positive, only 5 DLBL cases exhibited MSI. The frequency of MSI in DLBL was significantly higher than that in other types of TL and CLTH (P < 0.05). Four of 19 cases (21.1%) showed point mutation of the k-ras gene. The k-ras mutations occurred in the cases with DLBL with RER, and four of five cases with RER had a k-ras mutation, indicating a close association between RER and k-ras mutation. p53 mutations were not found in the CLTH. Two of 19 TL cases showed mutations of p53 gene. There was no significant association between RER and p53 mutation. These findings indicate that genomic instability contributes to the progression of TL from low grade to high grade, but not to the development of low grade lymphoma in CLTH lesions.

Adult↗
PubMed1999

HLA-A alleles of patients with pyothorax-associated lymphoma: anti-Epstein-Barr virus (EBV) host immune responses during the development of EBV latent antigen-positive lymphomas.

Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV) latent antigen-positive lymphoma resembling EBV-transformed lymphoblastoid cell lines (LCLs) and develops in non-immunocompromised patients. Thus, deficient anti-viral-antigen immune responses might be involved in the development of PAL. As MHC class I-restricted cytotoxic T lymphocytes (CTLs) are the major constituent of anti-viral immune responses, the HLA allele type and its expression may affect the development of PAL. Flow-cytometric analyses of PAL cell lines and LCLs using the W6/32 monoclonal antibody revealed that expression of HLA class I varied among cell lines. Although one PAL cell line, OPL-2, exhibited low expression, an LCL and another PAL cell line, OPL-1, strongly expressed HLA class I. Among the EBV latent infection genes, EBV nuclear antigens 2, 3, 4 and 6 and latent membrane proteins can induce efficient CTL responses in combination with HLA-A2 or -A11. HLA-A alleles of PAL patients were determined using low-resolution PCR-based typing with HLA-A locus sequence-specific primer combinations. The antigen frequencies of HLA-A2 and -A11 in PAL patients were not significantly different from those in the normal Japanese population. Although HLA class I antigen should be expressed during the course of lymphomagenesis, no HLA-A alleles influenced the development of overt PALs.

Aged↗
PubMed1999

Immunophenotypic and genotypic characterization of nasal lymphoma with polymorphic reticulosis morphology.

Nasal lymphoma with polymorphic reticulosis (PR) morphology is now categorized as T/natural killer (T/NK) cell lymphoma. In this study, immunophenotypes and genotypes of proliferating cells in 21 cases with PR were examined. The patients included 13 men and 8 women ranging in age from 20 to 74 (median 37) years. All patients presented with lesions in the upper respiratory tract, mostly in the nasal cavity. Histological specimens obtained from the primary lesions (19 cases) and metastatic cervical lymph nodes (2 cases) were used for analyses. Histologically, polymorphous proliferation was found in 20 cases, and these were thus diagnosed as PR. A monomorphous pattern was found in the remaining last case. Immunohistochemical analysis revealed that the proliferating cells were CD56 (123C3)+ and/or CD16 (2H7)+, TIA-1+ and frequently stained CD3 epsilon+. Tumor cells were frequently stained positively with monoclonal antibodies (mAbs) for T lymphocytes, but were negative for T-cell receptor (TCR) beta and delta chain expression. In situ hybridization analysis using an Epstein-Barr virus-encoded early RNA 1 (EBER-1) probe revealed positive signals in 13 of the 15 cases examined. Southern blotting analysis for clonality of the Epstein-Barr virus (EBV) genome in 12 positive cases confirmed the presence of monoclonal proliferation in 7 cases. The pattern of TCR gamma chain gene rearrangement was examined by PCR analysis of DNA from tumor tissues by the denaturing gradient gel electrophoresis method. The results demonstrated no clonal rearrangement in any of the 21 cases examined, including 7 cases with proven clonal proliferation of EBV-infected cells, indicating the absence of T-cell clones. Our findings strongly suggested that nasal T-cell lymphoma is in fact a NK cell lymphoma.

Adult↗
PubMed1999

Human HKR isozyme: organization of the hexokinase I gene, the erythroid-specific promoter, and transcription initiation site.

We previously described a cDNA for the human HKR isozyme, whose sequence is identical to that of the ubiquitous HKI isozyme, except for a unique 5' end sequence. Screening a human genomic library with a DNA fragment containing an erythroid-specific sequence we found one clone including 5' ends for both HKR and HKI genes. The first HKR exon was located 3 kb 5' of the first HKI exon. These results confirmed that HKR is produced from the HKI gene by alternate promoter and splicing. The HKI gene consisted of 19 exons. All exon-intron boundaries are conserved among the genes for hexokinase and glucokinase. The HKI gene length was estimated at over 67 kb. The initiation site for the HKR was identified by primer extension. Its promoter did not have a canonical TATA box, but an inverted GATA at nt -177 (i.e., 36 nt 5' to the transcription initiation site). In the HKR promoter a DNA fragment spanning nt -275 to nt -107 exhibited erythroid-specific activity. However, this was absent in shorter promoter fragments (nt -206 to -107 or nt -229 to -107). The sequence nt -275 to -229, which appeared critical for the erythroid-specific expression of the HKR gene, contained a consensus motif for Sp-1 and GATA, CCAAT, and GGAA motifs. The electrophoretic mobility shift assay (EMSA) suggested erythroid-specific cooperative protein-protein interaction in this region. Deletion of the GATA sequence as well as reaction with a specific antibody identified GATA-1 as one of the interacting proteins.

5' Untranslated Regions↗
PubMed1999

Increased activity of membrane glycoprotein PC-1 in the fibroblasts from non-insulin-dependent diabetes mellitus patients with insulin resistance.

Although most of patients with non-insulin-dependent diabetes mellitus (NIDDM) have insulin resistance, it is unknown whether a molecule might interfere with insulin action. Membrane glycoprotein PC-1 (plasma cell antigen-1), which inhibits insulin receptor tyrosine kinase activity, was isolated from fibroblasts of NIDDM patients. Because PC-1 content in skeletal muscle and adipose tissue correlated with whole body insulin sensitivity, PC-1 might play a role in insulin resistance. In order to know whether PC-1 activity of fibroblasts is also elevated in Japanese NIDDM patients, and whether PC-1 activity correlates with the parameters of insulin resistance in vivo or not, we measured PC-1 activity of cultured fibroblasts from 17 patients with NIDDM and seven healthy controls. PC-1 activity of the NIDDM patients was 85.2 +/- 33.1 nmol/mg per min (mean +/- S.D.), and was higher than that of healthy controls (42.6 +/- 12.7 nmol/mg per min, P = 0.0002). Insulin sensitivity was measured in 11 of 17 NIDDM patients by the artificial pancreas. PC-1 activity of the patients with insulin resistance (glucose infusion rate < 3.0 mg/kg per min, n = 7) was elevated to 99.9 +/- 31.9 nmol/mg per min, while that of the other patients (n = 4) was 55.3 +/- 7.5 nmol/mg per min (P = 0.003). In conclusion, glycoprotein PC-1 activity of dermal fibroblasts is correlated with insulin resistance in patients with NIDDM.

Adult↗
PubMed1999

Correlation of clinical features and telomerase activity in human gliomas.

Telomerase is a ribonucleoprotein containing an RNA template that synthesizes telomeric DNA. The expression of telomerase activity is concomitant with the attainment of immortality in tumor tissues and cells. In this report, we analyzed telomerase activity in 39 human gliomas with different histological, and in 10 meningiomas, 3 neurinomas, and 2 normal brain tissues by using a polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assay. Telomerase activity was detectable in almost all of the gliomas (36 of 39), but not in any of the meningiomas, neurinomas, or normal brain tissues. In addition, we also analyzed the level of telomerase activity in the 36 gliomas with positive telomerase activity. The relative telomerase activity of the glioma showed a clear association with the pathological grade of glioma; i.e., most of the tumors with high telomerase activity were pathologically of high grade. And also the relative level of telomerase activity could be correlated with the survival time of the patients. These results suggest that the level of telomerase activity in brain tumors is a diagnostic marker indicating the prognosis of the patient as well as the malignant potential of the tumor.

Astrocytoma↗
PubMed1999

Apoptotic changes precede mitochondrial dysfunction in red cell-type pyruvate kinase mutant mouse erythroleukemia cell lines.

Two erythroleukemia cell lines have been established from the splenic lesions of red blood cell-type pyruvate kinase (R-PK) activity-deficient mice of CBA/N origin infected with a polycythemic strain of Friend leukemia virus complex (FVp). Ten to 30% of the cells of these cell lines undergo apoptotic changes in routine passage, as shown by nuclear fragmentation, DNA laddering, DNA content (propidium iodide (PI) staining), and annexin V binding assay. In these cells, however, although adenosine 5'-triphosphate (ATP) levels were lower than in the control cells, the mitochondrial inner transmembrane potential (delta psi m), detected by rhodamine 123 (R123) and diSC3(5) staining, remained unchanged until the final stage of apoptosis. No evidence was obtained to relate this finding to R-PK mutation due to difficulty in cloning stable, conditionally inducible R-PK gene transfectants. However, low delta psi m in the apoptotic cell population of the control T3-K-1 (K-1) and T3-CI-2-0 (2-0) Friend erythroleukemia cells supports a possible relationship, as do results obtained in two Friend erythroleukemia cells recently isolated from normal CBA/N mice. These cell lines are expected to be useful for clarifying both the primary apoptotic changes independent of mitochondrial dysfunction and the PK-isozyme changes during erythrodifferentiation, for example, the decreased muscle type 2 (M2) PK level. Modification of growth signals in these cell lines may modulate differentiation and/or apoptosis and allow further elucidation of the signaling networks.

Adenosine Triphosphate↗
PubMed1999

[An experimental study of the protective effect of lazaroid (U-74389G) on cisplatin-induced toxicity].

Lazaroids, a novel series of 21-aminosteroids without glucocorticoid action, have the properties of free radical scavenging and potent inhibition of lipid peroxidation. U-74389G is one of the Lazaroid compounds. These compounds have shown excellent effect on central nervous system trauma and ischemia in experimental animals. The present study was designed to investigate whether Lazaroid (U-74389G) has a protective effect on Cisplatin (CDDP)-induced toxicity. Fisher 344 rats were used in this study. The animals were divided into three groups: I) CDDP 0.9 mg/kg i.v. alone; II) CDDP 0.9 mg/kg i.v. 1 hr after the p.o. administration of U-74389G 10 mg/kg; III) physiological saline 2.5 ml/kg i.v. instead of CDDP, for 7-10 days. First, the protective effect of Lazaroid (U-74389G) on CDDP-induced ototoxicity was studied. Cochlear damage was evaluated by means of the compound action potential (CAP) and histological examination using scanning electron microscopy. The degree of elevation of CAP thresholds and the rate of missing outer hair cells were significantly reduced in Group II as compared to Group I. These results clearly demonstrate that Lazaroid (U-74389G) has a protective effect on CDDP-induced ototoxicity. Second, the protective effect of Lazaroid (U-74389G) on CDDP-induced nephrotoxicity was studied. Nephrotoxicity was evaluated by means of serum BUN level and histopathological examination. There was no significant difference in serum BUN level and little difference of renal histopathological findings between Group I and Group II. Lazaroid (U-74389G) was not found to ameliorate CDDP-induced nephrotoxicity. Third, the influence of Lazaroid (U-74389G) on the antitumor effect of CDDP was investigated in rats inoculated subcutaneously with SCC-158 squamous-cell carcinoma cells. There was no significant difference of Tumor Growth Rate (TGR) between Group I and Group II. The result suggests that the combined administration does not alter the antitumor activity of CDDP. In conclusion, the combined administration of CDDP with Lazaroid (U-74389G) ameliorates CDDP-induced ototoxicity without decreasing the antitumor activity of CDDP.

Animals↗
PubMed1999

[Experimental studies of the protective effect of ginkgo biloba extract (GBE) on cisplatin-induced toxicity in rats].

Cisplatin (CDDP) is an effective antineoplastic agent in the treatment of solid malignant tumors. Its clinical use, however, is limited because of various side effects including sensorineural hearing loss. Several agents have been proposed to reduce these side effects. GBE has recently been reported to scavenge superoxide and hydroxyl radicals, resulting in a reduction of lipid peroxidation. GBE is expected to protect against CDDP-induced toxicity because its generative mechanism is thought to be associated with free-radical formation. The purpose of the present study was to evaluate GBE's efficacy as a protective agent against cisplatin-induced ototoxicity. Fisher rats were used in this study and were divided into three treatment groups: 1) animals administered 1.0 mg of CDDP per kg for 10 days (Group I), 2) animals receiving 100 mg of GBE per kg 90 min before administration 1.0 mg of CDDP per kg (Group II) and 3) a vehicle control (Group III). First, the protective effect of GBE on CDDP-induced ototoxicity was investigated. The auditory threshold was evaluated by means of the compound action potential (CAP) recording. After CAP recordings, cochlear sensory epithelia were observed throughout the cochlea by scanning electron microscopy. In Group II, the elevation of CAP thresholds at 12 kHz, 16 kHz, 20 kHz and the missing rate for the outer hair cells were significantly reduced as compared to those in Group I. These data suggest that GBE is effective for otoprotection against CDDP. Second, the protective effect of GBE on CDDP-induced nephrotoxicity was evaluated. Nephrotoxicity was evaluated by means of measurement of serum BUN and creatinine and histopathological examination of the kidney. These were significant differences in serum BUN and creatinine levels between Group I and Group II. Third, the influence of GBE against the antitumor effect of CDDP was researched in the rats inoculated subcutaneously with SCC-158 squamous cell carcinoma cells. There was no difference in tumor growth rate (TGR) between Group I and Group II. The result suggested that the combined administration had no influence on the antitumor activity of CDDP. In conclusion, the co-administration of CDDP with GBE is beneficial to ameliorate CDDP-induced toxicity without attenuation of CDDP antitumor activity.

Animals↗
PubMed1999

[In vitro activities of 23 antimicrobial agents against 4,993 gram-positive and gram-negative bacterial strains isolated from multicenter of Japan during 1994--in vitro susceptibility surveillance.Levofloxacin-Surveillance Group].

In a surveillance study conducted during 1994 at 24 medical institutes from different geographical areas of Japan, the susceptibility of clinical isolates to twenty three comparative agents, such as ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin, ampicillin, clavulanic acid/amoxicillin, oxacillin, piperacillin, cefaclor, cefotiam, cefdinir, cefclidin, ceftazidime, cefpirome, imipenem, aztreonam, vancomycin, minocycline, chloramphenicol, clarithromycin, sulfamethoxazole/trimethoprim, amikacin, and gentamicin, were tested by the standard broth micro-dilution method. A total of 4,993 isolates tested in this study included Streptococcus pneumoniae, methicillin susceptible Staphylococcus aureus (MSSA), methicillin resistant Staphylococcus aureus (MRSA), coagllase negative streptococci (CNS), Enterococcus faecalis, Enterococcus faecium, Enterobactericeae, Pseudomonas aeruginosa from patients with urinary tract infections or respiratory tract infections, and Haemophilus influenzae. For MSSA, S. pneumoniae, Enterobacteriaceae, and H. influenzae, more than 70% of the isolates was susceptible to fluoloquinolones. However, resistance occurred in more than 50% of MRSA and P. aeruginosa isolated from UTI. Fluoroquinolones were found to be effective against high level penicillin-resistant S. pneumoniae, the third generation cephem-resistant Enterobacteriaceae and ampicillin-resistant H. influenzae.

Anti-Bacterial Agents↗
PubMed1999

[Susceptibilities of Enterococcus faecium, PRSP and MRSA to RP59500 and their correlations with those to other drugs].

Investigations on emergence of vancomycin-resistant Enterococcus faecium (VREF) which has recently been attracting attention, especially in the Western countries, have been conducted in Japan. A total of 1,239 isolates of E. faecium were collected from 19 institutions during the period of April 1995 and June 1996, in the purpose of evaluating susceptibilities to variety of antimicrobial agents, including RP59500 and vancomycin (VCM), and detecting vancomycin-resistant genes (van genes). Susceptibilities of penicillin-resistant Streptococcus pneumoniae (PRSP) and methicillin-resistant Staphylococcus aureus (MRSA) were also studied. As a result, 2 isolates of E. faecium were found to be moderately resistant to VCM showing MIC of 8 micrograms/ml though the final identification in species level and the detection of van genes by PCR method have not been completed. On the other hand there detected no MRSA nor PRSP showing moderately resistant or resistant to VCM. It was concluded that RP59500 and VCM possessed favorable activity against clinically isolated E. faecium, PRSP and MRSA. Among other species of enterococci, moderately resistant strains to VCM showing MIC of 8 micrograms/ml were detected; 10 isolates of E. gallinarum, 4 of E. casseliflavus and 2 of E. flavescens. In those isolates, vanC1 and vanC2 were detected by PCR, and vanB was also detected in a isolates of E. gallinarum simultaneously.

Anti-Bacterial Agents↗
PubMed1999

Laparoscopic surgery assisted by a transvaginal approach.

We used laparoscopic surgery assisted by a transvaginal approach for gastrointestinal diseases. In the first case, a huge submucosal tumor enucleated laparoscopically from the minor curvature of the stomach was extracted through the vagina. In the second case, partial resection of the rectum to treat rectal endometriosis was performed laparoscopically with the assistance of manual handling inserted transvaginally. Although it can be applied only to female patients, especially to multipara, the vagina as an access point to the abdominal cavity can be widely used for various purposes in laparoscopic surgery.

Adult↗