Search PubMed⌕ Search

Biomedical subjects

H Kanno

Publications and source records attributed to H Kanno.

At least 37 records · Page 2Linked to original sources
PubMed2000

Low frequency of HLA-A*0201 allele in patients with Epstein-Barr virus-positive nasal lymphomas with polymorphic reticulosis morphology.

Lymphoproliferative diseases of the nasal cavity and paranasal sinuses occur frequently in Asian countries and are histologically categorized as monomorphic ordinary lymphoma and polymorphic reticulosis (PR) with apparent inflammatory cell infiltration. The large atypical cells in PR show natural-killer cell nature and frequently contain Epstein-Barr virus (EBV) DNA. Among the EBV genes involved in latent infection, those encoding EBV latent membrane proteins are frequently expressed in PR. Several cytotoxic T-lymphocyte (CTL) defined epitopes have been mapped to latent membrane proteins restricted with HLA-A2, -A11 or -A24 antigens. Thus, the HLA-A allele may affect the development of PR. To examine this possibility, HLA-A alleles of 25 patients with EBV(+) PR were determined with low-resolution polymerase chain reaction-based typing using HLA-A locus sequence-specific primer combinations. The frequency of HLA-A alleles including HLA-A2 and -A24 antigens in PR patients was lower than that in the normal Japanese population, but the difference was not significant. Since HLA-A2-restricted CTL responses are well delineated at the A2-subtype level, the A2-subtype of PR cases with HLA-A2 antigen was further determined by high-resolution genetic typing. The frequency of HLA-A*0201 in PR was significantly lower than in the normal population (p=0.0314). The HLA-A*0201-restricted CTL responses may thus function in vivo to suppress the development of overt lymphoma.

Adult↗
PubMed2000

Role of the von Hippel-Lindau tumor suppressor protein during neuronal differentiation.

The von Hippel-Lindau (VHL) tumor suppressor protein down-regulates transcription by transcriptional elongation enhanced by antagonizing elongin B and C. Transcriptional regulation is an important control mechanism for embryogenesis and tumorigenesis. The VHL gene and protein are expressed in neuronal cells of the fetal and adult brain. However, the role of the VHL gene in the central nervous system (CNS) has not been elucidated. The VHL gene might modify the expression of various genes during embryogenesis and tumorigenesis in CNS. We investigated the role of the VHL gene in CNS development using rodent CNS progenitor cells. Here we show that expression of the VHL protein is correlated with neuronal differentiation but not with glial differentiation in CNS progenitor cells, and we also show that VHL gene transduction induces neuronal differentiation. In addition, a VHL mRNA antisense oligonucleotide inhibits differentiation of CNS progenitor cells and up-regulates their cell cycle. In conclusion, the VHL gene plays an essential role in neuronal differentiation as well as transcription.

Animals↗
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

Effects of cyclic polylactate (CPL) on the growth of cloned leukemic cells in vitro.

A novel supramolecular oligomer, cyclic polylactate (CPL), was first discovered in the culture medium of HeLa-S tumour cells, and was reported to inhibit the growth of FM3A ascites tumour cells by inhibiting the activities of pyruvate kinase (PK) and lactic dehydrogenase (LDH). We have now synthesized CPL-containing oligomers with polymerization numbers ranging from 9 to 19, by prolonged heating and rapid mixing of a carbohydrate compound of the L-lactic acid monomer (C(3)H(6)O(3)) under decreased pressure and have studied its effects on the growth of leukemic cells. Treatment with 0.02 mg/ml CPL inhibited the growth of HL60 and TF-1 cells, while the growth of K562 cells was inhibited by 0.2 mg/ml CPL. A concentration of 2 mg/ml CPL was required to inhibit granulocyte-macrophage progenitor cell (CFU-GM) and burst-forming unit erythroid (BFU-E) precursor colony formation among normal bone marrow cells. Furthermore, 7A6 antigen expression and DNA ladder formation were observed in leukemic cells cultured with CPL, indicating that CPL induces apoptotic changes in these cells. These findings suggest that CPL might be a useful chemotherapeutic agent for leukemia.

Antineoplastic Agents↗
PubMed2000

Regulation of conjunctival goblet cell secretion by Ca(2+)and protein kinase C.

Conjunctival goblet cells secrete mucus in response to cholinergic (muscarinic) agonists, but the underlying signaling pathways activated in this tissue are not well understood. Cholinergic agonists usually activate phospholipase C to produce inositol 1,4,5 trisphosphate and diacylglycerol. Inositol 1,4,5 trisphosphate increases the intracellular Ca(2+)concentration ([Ca2(+)](i)) while diacylglycerol activates protein kinase C (PKC). PKC and Ca(2+), either by itself or with calmodulin, activate cellular functions. Goblet cell glycoprotein secretion, our index of mucin secretion, was measured from pieces of rat conjunctiva with an enzyme-linked lectin assay using the lectin Ulex europaeus agglutinin I (UEA-I). UEA-I selectively recognizes high molecular weight glycoproteins secreted by the goblet cells. Increasing the [Ca(+)](i)with the Ca(2+)ionophore ionomycin stimulated glycoprotein secretion from conjunctival goblet cells. Cholinergic agonist-induced secretion was completely blocked by chelation of extracellular Ca(2+)and by the Ca(2+)/calmodulin-dependent protein kinase inhibitors KN93 and W7 as well as their inactive analogs KN92 and W5. Activation of classical and novel PKC isozymes by phorbol 12-myristate 13-acetate and phorbol 12,13-dibutyrate stimulated goblet cell glycoprotein secretion. When ionomycin and PMA were added simultaneously, secretion was additive. PKC isozymes were identified by Western blotting analyses with antibodies specific to nine of the 11 PKC isozymes (PKCgamma and zeta were not tested). All nine PKC isozymes were identified in the conjunctival epithelium. The cellular location of the PKC isozymes was determined by immunofluorescence microscopy. Goblet cells contained the classical PKC isozymes PKCalpha, -betaI and -betaII, the novel PKC isozymes PKCepsilon, -theta;, and - mu, and the atypical PKC isozyme PKCzeta. We were unable to determine if PKC activation is required for cholinergic-agonist induced secretion because the PKC inhibitors chelerythrine and staurosporine alone greatly increased secretion. We conclude that Ca(2+)plays a major role in cholinergic agonist-induced conjunctival goblet cell secretion, but this agonist appears not to use Ca(2+)/calmodulin-dependent protein kinases. We also conclude that activated PKC can stimulate goblet cell secretion and that seven different PKC isoforms are present in the goblet cells.

Animals↗
PubMed2000

Molecular cloning and expression profile of rat myocilin.

Myocilin is known to be associated with the pathogenesis of juvenile-onset primary open angle glaucoma. The tissue distribution of myocilin transcripts has been analyzed in both humans and mice, and a high level of expression in the retina and skeletal muscle has been reported. The functions of myocilin in these tissues are unknown. We isolated rat myocilin cDNA and examined the expression pattern of myocilin, including its expression in endocrine organs, using Northern blot analysis. The rat myocilin cDNA sequence has two in-frame initiation codons, the upstream and downstream ATGs corresponding to the initiation codon of human and murine myocilin, respectively. It is most likely that the first ATG is a translational initiation codon, since 8 of 13 amino acid residues deduced from the rat cDNA sequence between the first and the second ATGs are the same as those in human myocilin. The open reading frame encodes 502 amino acids. Rat myocilin also has both a myosin-like domain and an olfactmedin-like domain, which have been identified in human and murine myocilin. Northern analysis of rat myocilin mRNA revealed substantial expression in the thyroid gland, as well as in the retina and muscle. No transcripts were detected in other endocrine glands, including the adrenal gland, pituitary, and testis. Myocilin may play an important role in thyroid function. Further study of the expression and role of myocilin in the thyroid is required.

Amino Acid Sequence↗
PubMed2000

Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan.

Glycogen storage disease type IIIa (GSD IIIa) is an autosomal recessive disorder caused by deficiency of the glycogen-debranching enzyme (AGL). Recent studies of the AGL gene have revealed the prevalent mutations in North African Jewish and Caucasian populations, but whether these common mutations are present in other ethnic groups remains unclear. We have investigated eight Japanese GSD IIIa patients from seven families and identified seven mutations, including one splicing mutation (IVS 14+1G-->T) previously reported by us, together with six novel ones: a nonsense mutation (L124X), a splice site mutation (IVS29-1G-->C), a 1-bp deletion (587delC), a 2-bp deletion (4216-4217delAG), a 1-bp insertion (2072-2073insA), and a 3-bp insertion (4735-4736insTAT). The last mutation results in insertion of a tyrosine residue at a putative glycogen-binding site, and the rest are predicted to cause synthesis of truncated proteins lacking the glycogen-binding site at the carboxyl terminal. Thirteen novel polymorphisms have also been revealed in this study: three amino acid substitutions (R387Q, G1115R, and E1343 K), one silent point mutation (L298L), one nucleotide change in the 5'-noncoding region, and eight nucleotide changes in introns. Haplotype analysis with combinations of these polymorphic markers showed L124X, IVS14+1G-->T, and 4216-4217delAG to be on different haplotypes. These results demonstrate the importance of the integrity of the carboxy terminal domain in the AGL protein and the molecular heterogeneity of GSD IIIa in Japan.

Amino Acid Sequence↗
PubMed2000

Induction of chromosomal aberrations and growth-transformation of lymphoblastoid cell lines by inhibition of reactive oxygen species-induced apoptosis with interleukin-6.

Etiological evidence, indicating the relationships between the onset of malignant lymphoma and pre-existing chronic inflammation, has been accumulated. For the autonomous growth of malignant tumor, genetic lesions, such as chromosomal aberrations, amplification of oncogenes, and mutations of genes involved in the cell cycle regulation, must be essential. However, how the inflammation promotes the accumulation of genetic lesions and induces the autonomous growth of lymphoid cells remains unclear. Reactive oxygen species released by polymorphonuclear leukocytes and macrophages are factors causing DNA damage in the foci of inflammation, and thus could play a role in lymphomagenesis. The xanthine/xanthine oxidase (X/XOD) system produces a mixture of hydrogen peroxide and superoxide anion extracellularly, and thus serves as an in vitro source of reactive oxygen species. Cell death of lymphoblastoid cell lines (LCLs) was induced with X/XOD treatment in a dose-dependent manner. DNA fragmentation, which is the characteristic feature of apoptosis, was observed in LCLs at 4-8 hours after X/XOD treatment. Among cytokines such as interleukin-6 (IL-6), IL-10, and interferon-gamma, only pretreatment with IL-6 gave LCLs the resistance to X/XOD-induced cell death in a dose-dependent manner. The proportion of apoptotic cells in X/XOD-treated LCL culture was decreased with IL-6 pretreatment by quantification with flow cytometric analysis. Treatment of LCLs with IL-6 for 48 hours up-regulated bcl-2 mRNA expression. Furthermore, the LCLs repeatedly treated with X/XOD and cultured with or without IL-6 showed many more structural abnormalities of chromosomes than those without X/XOD treatment. Colony forming efficiency of X/XOD-treated LCLs with IL-6 was significantly higher than those without IL-6, and even relatively higher than LCLs without X/XOD treatment. IL-6 could support the survival of non-neoplastic B cells and accelerate the malignant transformation of B lineage cells in inflammatory lesions.

Apoptosis↗
PubMed2000

Hexokinase: gene structure and mutations.

Hexokinase (HK) deficiency is a rare red cell enzyme deficiency associated with hereditary non-spherocytic haemolytic anaemia; to date, only 17 affected families have been reported. Human HK has four major isozymes, each of which is encoded by a separate gene. Recent studies have shown that both ubiquitously expressed type I HK (HK-I) and erythroid-specific HK-R are expressed in erythrocytes, and that these isozymes are encoded by the single HK-I gene. The human HK-I gene has 19 exons, the HK-I and HK-R transcripts being produced by using two distinct promoters. Thus, the first and second exons are specifically utilized for the erythroid-specific HK-R and ubiquitously expressed HK-I isozymes respectively. So far, only two HK variants have been analysed at the molecular level. Since the human HK-I crystal structure has recently been elucidated, the molecular analysis of the HK variants will be useful for discussing the structure-function relationship of the enzyme.

Amino Acid Sequence↗
PubMed2000

Expressions of Fas ligand and other apoptosis-related genes and their prognostic significance in epithelial ovarian neoplasms.

Expression of apoptosis-related proteins, bcl-2, Bax, Fas and Fas ligand (L), in ovarian epithelial neoplasms together with its clinical relevance was examined by immunohistochemistry. They included 36 cases with adenoma, 33 with low potential malignancy (LPM) and 63 with carcinomas. bcl-2 expression was observed in 14 of 36 cases (39%) with adenoma, five of 33 (15%) with LPM (P< 0.05) and 12 of 63 (19%) with carcinoma (P < 0.05). Cases with bcl-2 expression showed more favourable prognosis than those without, but the difference was not statistically significant. There was no difference in frequency of Bax and Fas expression between each histologic category. Fas L expression was observed in one of 36 cases (3%) with adenoma, but in 12 of 33 (36%) with LPM (P < 0.001) and 42 of 63 (67%) with carcinoma (P < 0.0001). In carcinomas, cases expressing Fas L showed a less favourable prognosis than those without (P = 0.02). Density of CD8+ lymphocytes, possibly cytotoxic T-cells, was higher in serous carcinoma with negative Fas L expression than those with positive Fas L expression. These findings suggest that Fas L expressing carcinomas induce apoptosis in infiltrating CTL with Fas expression, and escape from immune surveillance.

Adenoma↗
PubMed2000

Pyruvate secreted by human lymphoid cell lines protects cells from hydrogen peroxide mediated cell death.

Reactive oxygen species (ROS) released from polymorphonuclear leukocytes and macrophages could cause DNA damage, but also induce cell death. Therefore inhibition of cell death must be an important issue for accumulation of genetic changes in lymphoid cells in inflammatory foci. Scavengers in the post culture medium of four lymphoid cell lines, lymphoblastoid cell lines (LCL), Raji, BJAB and Jurkat cells, were examined. Over 80% of cultured cells showed cell death 24 h after xanthine (X)/xanthine oxidase (XOD) treatment, which was suppressed by addition of post culture medium from four cell lines in a dose-dependent manner. H2O2 but not O2*- produced by the X/XOD reaction was responsible for the cytotoxity, thus we used H2O2 as ROS stress thereafter. The H2O2-scavenging activity of post culture media from four cell lines increased rapidly at the first day and continued to increase in the following 2-3 days for LCL, Raji and BJAB cells. The scavenging substance was shown to be pyruvate, with various concentrations in the cultured medium among cell lines. Over 99% of total pyruvate was present in the extracellular media and less than 1% in cells. alpha-Cyano-4-hydroxycinnamate, a specific inhibitor of the H+-monocarbohydrate transporter, increased the H2O2-scavenging activity in the media from all four cell lines via inhibition of pyruvate re-uptake by cultured cells from the media. These findings suggest that lymphoid cells in inflammatory foci could survive even under ROS by producing pyruvate, so that accumulation of lymphoid cells with DNA damage is possible.

Cell Death↗
PubMed2000

Haemophilus influenzae infection and Guillain-Barré syndrome.

It has been reported recently that Haemophilus influenzae can elicit an axonal form of Guillain-Barré syndrome. To investigate the incidence and features of H. influenzae-related Guillain-Barré syndrome, anti-H. influenzae antibody titres were measured by enzyme-linked immunosorbent assay (ELISA) in 46 consecutive Japanese patients with Guillain-Barré syndrome, 49 normal controls, 24 patients with multiple sclerosis and 27 patients with amyotrophic lateral sclerosis (ALS). Whole bacteria of non-encapsulated (non-typable) H. influenzae isolated from one of the Guillain-Barré syndrome patients was the antigen used. Elevated anti-H. influenzae antibodies for two or three classes of IgG, IgM and IgA were found in six (13%) Guillain-Barré syndrome patients, but not in the normal controls and patients with multiple sclerosis or ALS. The incidence was significantly higher in patients with Guillain-Barré syndrome than in the normal controls (P = 0.01) and patients with multiple sclerosis or ALS (P = 0.009). Western blot analysis confirmed that the H. influenzae-positive patients' IgG recognized the lipopolysaccharides of H. influenzae. Guillain-Barré syndrome patients with anti-H. influenzae antibodies showed relatively uniform clinical and laboratory features: prodromal respiratory infection, less frequent cranial and sensory nerve involvement, pure motor axonal degeneration on electrophysiology, and positivity for IgG anti-GM1 antibodies. Although the features were similar to those in Guillain-Barré syndrome patients infected by Campylobacter jejuni, the recoveries seemed to be better in patients with H. influenzae-related Guillain-Barré syndrome. It is concluded that a form of Guillain-Barré syndrome occurs after respiratory infection by H. influenzae in the Japanese population. A particular strain of non-typable H. influenzae has a ganglioside GM1-like structure and elicits axonal Guillain-Barré syndrome similar to C. jejuni-related Guillain-Barré syndrome.

Adult↗
PubMed2000

Connection designs of three different implant systems in the resorbed edentulous maxilla: a case report.

This report presents the mixed use of three different system implants for an implant-supported fixed bridge in a resorbed maxilla. Two of six implants that had been placed were lost. New implants were combined with the remaining implants that had been placed by the previous dentists in 1992 and 1997. The three implant systems consisted of the following: one incorporated an intramobile element into an implant device, and the other two were whole titanium screw-type implants (one with a machined surface and the other with a plasma-sprayed surface). This clinical report describes the connection designs of these different system implants to the fixed bridge and lists the complications that followed.

Bone Resorption↗
PubMed2000

Analysis of T-cell antigen receptor gamma chain gene rearrangement by polymerase chain reaction in combination with denaturing gradient gel electrophoresis in the differential diagnosis of cutaneous T-lymphoproliferative diseases.

A polymerase chain reaction (PCR)-based strategy has been developed for analysis of clonal rearrangement of the T-cell receptor gamma gene (TCR gamma) and was shown to be useful for detection of clonal T-cell populations. In this study, we performed PCR combined with denaturing gradient gel electrophoresis (DGGE) on fresh frozen biopsy samples from 16 patients with cutaneous T-lymphoproliferative diseases in whom a definite diagnosis was difficult to make on morphological and immunohistochemical grounds alone. Ages of the patients at biopsy ranged from 28 to 81 (median 62) years, and the subjects consisted of 8 men and 8 women. They presented with erythema on the extremities in 5 cases, trunk in 7, buttock in 2, and papules on the trunk and face in one case each. Clonal rearrangement of TCR gamma was observed in 3 of 16 cases. Clinical diagnoses of these three cases were mycosis fungoides, cutaneous invasion of adult T-cell leukemia (ATL), and large granular lymphocytic leukemia (LGL) of T-cell type, respectively, but they were histologically difficult to differentiate from reactive cutaneous T-cell proliferation. The skin lesions of the LGL case worsened, and this patient died two years after biopsy. Another patient with suspected mycosis fungoides in the plaque stage died due to dissemination of tumors 22 months after biopsy. The remaining one patient with ATL survived with cutaneous lesions for over four years. Clonality was not demonstrated in the remaining 13 cases, and their clinical courses were favorable. These findings showed that demonstration of clonal TCR gamma gene rearrangement using the PCR-DGGE method is very helpful for diagnosis of cutaneous T-cell neoplasms.

Adult↗
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↗
PubMed2000

[The present status of susceptibility tests for detection of antibiotic-resistant bacteria in Japan].

Recently, NCCLS Susceptibility tests have been widely used in Japan. NCCLS Susceptibility tests are one of the most excellent systems in the world. However, there are some differences in the type of antibiotic-resistant bacteria and systems of chemotherapy between Japan and the USA. To use NCCLS methods more effectively in Japan, it is necessary to make a partial amendment concerning with the choice of antibiotics and break points of resistance.

Ampicillin Resistance↗