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H Kanno

Publications and source records attributed to H Kanno.

At least 19 recordsLinked to original sources

Somatic mutations of the von Hippel-Lindau tumor suppressor gene and loss of heterozygosity on chromosome 3p in human glial tumors.

Molecular genetic analysis of von Hippel-Lindau tumor suppressor gene (VHL gene) was performed on 38 tissues of human glial tumors (ependymoma, 1; astrocytoma, 6; oligodendroglioma, 1; oligoastrocytoma, 2; anaplastic oligoastrocytoma, 3; anaplastic astrocytoma, 14; glioblastoma multiforme, 11). Somatic DNAs extracted from frozen tumor specimens were examined by single-strand conformational polymorphism analysis and direct sequencing. In addition, loss of heterozygosity (LOH) on chromosome 3p in 15 glial tumor cases, lymphocyte DNAs of which were available, was examined by use of 10 microsatellite probes and two polymorphism markers for the VHL gene. Two cases of low-grade gliomas showed somatic sense mutations in exon 3 of the VHL gene, and 6 of 15 cases (40.0%) showed LOH of chromosome 3p. The VHL gene-mutated cases also showed LOH. The retention of heterozygosity and high pathological grade of glial tumors were correlated significantly. In addition, Kaplan-Meier survival analysis for patients with glial tumors showed that patients with LOH had a significantly longer survival time than those without LOH. These results suggest that somatic mutations on 3p, including the VHL gene, may be involved in tumorigenesis of some low-grade glial tumors.

Adult

Thoracoscopic surgery combined with a supraclavicular approach for removing superior mediastinal tumor.

This report introduces our new technique of thoracoscopic surgery combined with a supraclavicular approach for removing superior mediastinal tumor. A 68-year-old woman noticed a tumor palpable in the left supraclavicular fossa. The patient had no pain around the neck and shoulder. A radio-opaque shadow 6 cm in diameter was detected in her left apical lung field on chest roentgenogram. Chest CT and MRI showed that the tumor was located in the superior mediastinum, extending up to the thoracic inlet, and there was no invasion of the surroundings. At first, a thoracoscopic examination was performed to assess the possibility of the excision. After dissecting the tumor from the mediastinal tissue and the first costovertebrae as far as possible by thoracoscopic surgery, a supraclavicular approach was used to enter the thoracic cavity. Complete resection of the tumor was successfully performed by thoracoscopic surgery combined with a supraclavicular approach. The tumor was removed in a plastic bag through the supraclavicular defect. Postoperative histopathology revealed that the tumor was a benign neurogenic one. A satisfactory follow-up of 5 postoperative days was observed without any complications, and the patient was discharged. The procedure was safe, easy, and minimally invasive to perform. Moreover, the supraclavicular approach could be used to add trocar port if needed.

Aged

Risk of cytomegalovirus infection after peripheral blood stem cell transplantation.

From 1992 to 1995, 105 patients received PBSCT in our hospitals and we observed no incidence of CMV-pneumonia. To clarify whether activation of CMV occurs in these patients shell vial cultures, CMV antigenemia and PCR (DNA-PCR and RT-PCR) were used as detection methods for CMV. Bronchoalveolar lavage (BAL) samples, MNC and PMN samples from peripheral blood leukocytes, and urine samples were taken from 17 patients on day 35 after PBSCT. CMV was detected in one urine specimen but not detected in any of the BAL, MNC or PMN specimens by shell vial culture. CMV antigenemia provided no positive data. Nine of the 74 samples taken from the 17 patients proved positive by DNA-PCR, but all CMV-mRNA results were negative by RT-PCR. We performed CMV antigenemia and PCR on MNC and PMN specimens from six patients every 1 to 2 weeks after transplantation to determine whether and when CMV was activated. Two patients tested positive transiently by DNA-PCR but negative throughout by both antigenemia and RT-PCR. These results suggest that the risk of CMV infection is low because the incidence of CMV activation in patients receiving PBSCT is low.

Adolescent

Production of the immunosuppressive cytokine interleukin-10 by Epstein-Barr-virus-expressing pyothorax-associated lymphoma: possible role in the development of overt lymphoma in immunocompetent hosts.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Both cell lines contain EBV DNA, but only OPL-1 expresses EBV nuclear antigen 2, which works as a target molecule for the cell-mediated immune response. As systemic immunodeficiency is unlikely to be present in PAL patients, PAL from which OPL-1 derived was not expected to be fully developed. In this study, we examined the expression of immunosuppressive factors in OPLs. Only OPL-1, not OPL-2, expressed interleukin-10 (IL-10) mRNA and secreted IL-10 into culture supernatant. Both OPL-1 and OPL-2 expressed transforming growth factor (TGF)-beta 1 mRNA; however, neither expressed latent TGF-beta-binding protein mRNA at a detectable level by Northern blot analysis. Because TGF-beta expresses its functions in cooperation with latent TGF-beta-binding protein, the biological functions of TGF-beta 1 could be negligible. Neither cell line expressed at a detectable level EBV BCRF-1 mRNA, a viral gene product that is partly homologous to human IL-10 and shares biological activities of IL-10. Although IL-10 is reported to promote the growth of activated or neoplastic B cells, OPL-1 did not respond to human recombinant IL-10 by growing faster. As OPL-1 expresses a target antigen for the host cytotoxic T-cell response, the production of an immuno-suppressive cytokine, IL-10, might contribute to the development of overt lymphoma by inducing locally immunosuppressive circumstances. The present study suggests that an immunosuppressive cytokine plays a role in lymphomagenesis of immunocompetent patients.

Animals

[Pyothorax-associated lymphoma: EBV-positive lymphoma developing in immunocompetent patients].

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most of PALs are diffuse lymphomas of B cell type and contain Epstein-Barr virus (EBV) DNA. We established two lymphoma cell lines from biopsy specimens of PAL cases, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. The differences in growth rate and oncogene expression between the lines could not be adequately explained by the pattern of EBV latent gene expression. The subsequent genetic lesions might be necessary for the development of overt lymphoma. Furthermore, the mechanism of development of viral antigen-positive tumor in immunocompetent patients is discussed.

Empyema, Pleural

Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia.

We report here two new cases of glucose phosphate isomerase (GPI) deficiency associated with hemolytic anemia and present the results of molecular analysis of the five Japanese GPI variants. A Japanese girl (GPI Fukuoka) had an episode of prolonged neonatal jaundice and at 3 years of age was admitted due to acute hemolytic crisis occurring with upper respiratory tract infection. Red blood cell (RBC) GPI activity was decreased to 11.8% of normal and the reduced glutathione (GSH) level of RBCs was slightly decreased. A 54-year-old Japanese man (GPI Iwate) was hospitalized due to chronic active hepatitis, and compensated hemolysis was noted. RBC GPI activity of the proband was decreased to 18.8%, and the GSH content was about half of the normal mean value. Sequencing of the reticulocyte GPIcDNA showed homozygous missense mutations 1028CAG-->CGG (343Gln-->Arg), 14ACC-->A7C (5Thr-->lle), 671ACG-->A7G (224Thr-->Met), and 1615GAC-->AAC (539Asp-->Asn) in GPI Narita, GPI Matsumoto, GPI Iwate, and GPI Fukuoka, respectively. We also identified GPI Kinki as a compound heterozygote of 1124ACA-->AGA(375Thr-->Arg)/ 1615GAC-->AAC(539Asp-->Asn). Our findings, together with the previous results of other investigators, showed that the GPI gene mutations so far identified were heterogeneous, although most GPI variants had common biochemical characteristics such as heat instability and normal kinetics. Several amino acid substitutions were identified in the proximity of the catalytically important amino acid residues such as Ser/Asp 159/160, Asp341, and Lys518, which have been identified in the structural analysis of the pig GPI. The molecular characterization of human GPI variants, therefore, may provide new insights into the genotype-phenotype correlation of GPI deficiency as well as the structure-function relationship of this enzyme.

Anemia, Hemolytic

Expression of Epstein-Barr virus latent infection genes and oncogenes in lymphoma cell lines derived from pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of patients with long-standing pyothorax. The term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PALs are diffuse lymphomas of the B-cell type and contain Epstein-Barr virus (EBV) DNA. We have established 2 lymphoma cell lines from biopsy specimens of PAL cases, OPL-1 and OPL-2, and examined their growth characteristics and the expression of EBV latent infection genes and oncogenes. OPL-2 exhibited a more rapid growth and higher saturation density than OPL-1, and only OPL-2 exhibited colony-forming activity in soft agar. OPL-1 and -2 were positive for B-cell differentiation markers and showed clonal surface immunoglobulins. Both line contained a single predominant form of episomal EBV DNA, indicating clonal cellular proliferation of an EBV-infected progenitor cell. OPL-1 and -2 contained type B and A EBV genome, respectively. Expression of EBV nuclear antigen (EBNA)2 mRNA and protein was detected by Northern and Western blot analysis in OPL-1, but not in OPL-2. On the other hand, the expression of latent membrane protein (LMP)1 mRNA in both OPL-1 and -2 was extremely weak and detectable only by reverse transcription-polymerase chain reaction. Protein expression of LMP1 was not observed by Western blot analysis or immunocytochemistry. Both lines expressed c-myc mRNA. Only OPL-1 expressed mRNA of c-fgr, an oncogene whose expression is upregulated by EBNA2. Both OPLs expressed bcl-2 mRNA without detectable expression of LMP1 protein.

Aged

Three cases of hereditary nonspherocytic hemolytic anemia associated with red blood cell glutathione deficiency.

Three unrelated Japanese patients with chronic nonspherocytic hemolytic anemia wer found to have marked deficiency of red blood cell (RBC) reduced glutathoine (GSH) (4.4%, 13.1%, and 6.9% of normal, respectively). A panel of RBC enzyme assays showed that one patient had decreased glutathione synthetase activity and the other two were moderately deficient in gamma-glutamylcystine synthetase. Some family members of each patient showed mild deficiency of the respective enzymes. RBCs of these patients also showed a decreased level of glutathione-S-transferase as in previously described GSH-deficient cases. Hemolytic anemia was their only manifestation, and neither 5-oxoprolinemia nor 5-oxoprolinuria, which are usually associated with to generalized type of glutathione synthetase deficiency, was noted in our patients.

Adolescent

Epstein-Barr virus in Hodgkin's disease patients in Japan.

BACKGROUND: The association of Epstein-Barr virus (EBV) and Hodgkin's disease (HD) has been suggested by serologic, epidemiologic, and molecular biologic studies. The high level of EBV association with HD in the developing countries was discussed in relation to the high HD incidence in these areas. Japanese HD shows a distinct peak incidence in older adults. In contrast, Western HD shows a bimodal pattern, the first peak in young adulthood and a second peak in older patients. In the present study, the EBV association with HD in Japan was investigated, and the results were compared with those reported from industrialized and developing countries. METHODS: Fifty-seven patients with HD were studied for the presence or absence of the EBV genome by the polymerase chain reaction and in situ hybridization methods. Seven cases were excluded from the analysis for EBV because of poor preservation of nucleotides in the specimens. RESULTS: EBV genomes were detected in the Reed-Sternberg (R-S) cells of 32 of the 50 patients examined (64%). The EBV association was independently affected by histologic subtype (84% in mixed cellularity and 44% in others), sex (76% in males and 31% in females), and age (76% in patients aged 40 years and older and 38% in patients younger than 40 years of age; P < 0.01). High EBV association is found at the peak in older adults predominantly with mixed cellularity type. Previous studies revealed that the high EBV was associated with the older peak of the bimodal peaks in Western HD, and a unimodal peak in childhood in developing countries. The EBV subtype was predominantly type A, which is identical to the immunocompetent type of HD reported previously. CONCLUSIONS: The results of the current study, together with those reported previously, showed that the presence of the Epstein-Barr virus correlated with mixed cellularity type, age older than 40 years, and male sex.

Adolescent

Prognostic factors in angiosarcoma: a multivariate analysis of 55 cases.

Data for prognostic factors in angiosarcoma (AS) are limited, prompting a large-scale study of AS with multivariate analysis. To analyze prognostic factors in angiosarcoma (AS), clinical and histologic findings in 55 patients collected from hospitals in Japan were reviewed. Prognostic factors were evaluated by univariate and multivariate Cox's proportional hazards models. The study involved 32 males and 23 females, ages 18-93 (median, 69) years. The primary sites of tumors included head and neck (32 cases), trunk (10), extremities (3), spleen (3), breast (3), and other (4). The overall 2-year survival rate was 21%. Univariate analysis of clinical factors including age, sex, size and depth of tumor, tumor-related symptoms, interval between onset of symptoms and admission, surgical procedures, adjuvant chemotherapy, and adjuvant radiotherapy showed that age, tumor size, and mode of treatment were significant for survival. Histologic factors analyzed were mitotic counts, cellularity, cellular pleomorphism, extent of necrosis, vascular differentiation, and nonspecific diagnosis. Only mitotic counts were significant for prognosis. Multivariate analysis on these four factors revealed that tumor size, mode of treatment, and mitotic counts were independent prognostic factors.

Adolescent

Laparoscopic reconstruction of vagina using sigmoid autograft.

With the advent of advanced laparoscopic techniques in surgery, new applications have been found, which have expanded the role of laparoscopy in the gynecological field. The aim of this paper is to introduce our laparoscopic technique of taking a sigmoid colon autograft for colpopoiesis in a patient with congenital agenesis of the vagina. This technique is less invasive and is easy to perform, and it may be the best choice of operation in respect to the naturalness and the permanency of the vagina that results. The success of this laparoscopic technique of taking a sigmoid autograft for colpopoiesis suggests diverse possible applications in the future.

Adult

A new method of the electrolyte-free long-term preservation of human sperm at 4 degrees C.

OBJECTIVES: To develop a new method for the long-term preservation of human sperm. SETTING: Andrology laboratory of our hospital. PATIENTS: Thirty-one normal and 19 asthenozoospermic semen samples obtained from patients attending our infertility clinic. The average sperm motility was 70.2% and 36.0% in the normal and asthenozoospermic groups, respectively. INTERVENTIONS: Ejaculated sperm were centrifuged and washed using the electrolyte-free Percoll gradient and then were preserved at 4 degrees C. MAIN OUTCOME MEASURES: The motility of the preserved sperm was analyzed using computer-assisted semen analyzer after the addition of Ham's modified F-10 (GIBCO, Grand Island, NY). RESULTS: In the normal group, motility rate after the addition of Ham's F-10 for 1, 2, and 4 weeks of preservation was 65.4%, 40.4%, and 5.5%, respectively. In the asthenozoospermic group, motility rate after 1 and 2 weeks of preservation was 31.3% and 18.1%, respectively. Preservation solutions containing sodium or potassium decreased motility after preservation. Restoration of preserved sperm was not achieved by incubation alone; however, reinitiation was induced by incubation together with Ham's F-10. CONCLUSIONS: Human sperm in the electrolyte-free solution survived for a long period of time at 4 degrees C and reinitiation of sperm motility after preservation required the addition of Ham's F-10.

Cold Temperature

The role of potassium ion and extracellular alkalization in reinitiation of human spermatozoa preserved in electrolyte-free solution at 4 degrees C.

OBJECTIVE: To elucidate reinitiation factors in human spermatozoa preserved in the electrolyte-free solution at 4 degrees C. SETTING: Andrology laboratory of our hospital. PATIENTS: Semen samples were obtained from patients attending our infertility clinic. INTERVENTIONS: Ejaculated sperm were centrifuged and washed using the electrolyte-free Percoll gradient and then were preserved for 1 week at 4 degrees C. MAIN OUTCOME MEASURES: The motility of preserved sperm was incubated and analyzed after the addition of electrolyte solutions. RESULTS: The motility rate was 9.6% when the preserved sperm were incubated directly. The motility increased to 35.1% after alkalization (pH 7.8) and further increased to 40.7% when 0.1 mM KCl was added. The motility decreased to 1.4% in a weak acidic solution (pH 6.8), however, the addition of a > or = 10 mM concentration of NaCl or > or = 0.1 mM concentration of KCl increased in motility. The motility rate in 40 mM NaCl and 40 mM KCl (pH 6.8) was 19.8% and 31.5%, respectively. The restoration of motility by NaCl was inhibited by 1 mM amiloride. The motility also rose to 54.1% and 32.3% in 0.04% NH3 and 80 mM NH4Cl solution, respectively. CONCLUSIONS: The reinitiation of preserved spermatozoa was induced by potassium ion and extracellular alkalization.

Amiloride

Molecular genetic diagnosis of von Hippel-Lindau disease: analysis of five Japanese families.

We analyzed deoxyribonucleic acids from blood samples of five Japanese von Hippel-Lindau (VHL) disease families (three familial cases, two new mutations) for the presence of VHL gene mutations by single-strand conformational polymorphism analysis and direct sequencing. Four of the five families showed germ line mutations in VHL gene, comprising 2 missense mutations, 1 deletion, and 1 splice-site mutation. Two families had VHL gene mutations at exon 1; 1 family at exon 3; and 1 family at the splice-site adjacent to exon 3. Presymptomatic patients were accurately diagnosed by these methods. However, one family did not show a VHL gene mutation in the germ line but showed a somatic mutation at exon 2 in the hemangioblastoma tissue. The consequence of the somatic mutation was a microdeletion leading to a frameshift mutation. Our study is the first report of VHL gene analyses of Japanese VHL disease families, and suggests that not only germ line mutation, but also somatic mutation can lead to development of a tumor associated with the VHL disease.

Base Sequence

Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in women with or without gynecologic cancer.

OBJECTIVE: To detect the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG) which is an oxygen-radical-forming agent, in the urine of patients with (n = 18) or without (n = 10) carcinoma of the female genitalia. None of the patients had been receiving any treatment before their urinary 8-OHdG levels were measured. METHODS: Urinary 8-OHdG was extracted by a solid-phase technique, and its level was determined by high-performance liquid chromatography (HPLC) with an electric chemical detector (ECD). RESULTS: We determined that the urinary 8-OHdG level decreased with as the age of the patient increased, and was extremely high in advanced cancer and recurrent cancer in a considerable number of patients. The urinary 8-OHdG level (1,827 +/- 1,500 pmol/kg/day, mean +/- SEM) in 18 patients with carcinoma was significantly higher (p < or = 0.05) than that (747 +/- 425 pmol/kg/day) in 10 patients without carcinoma. CONCLUSION: These results suggest that it might be possible to determine the spread of cancer to some extent by determining a patient's urinary 8-OHdG level.

8-Hydroxy-2'-Deoxyguanosine

Inhibitory effects of sterols isolated from Chlorella vulgaris on 12-0-tetradecanoylphorbol-13-acetate-induced inflammation and tumor promotion in mouse skin.

Inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice was observed in the methanol extract of Chlorella vulgaris, a green alga. The hexane soluble fraction obtained from the methanol extract exhibited marked inhibitory activity from which were isolated two delta(5,7)-sterols (ergosterol and 7-dehydroporiferasterol), two delta(5,7,9(11))-sterols [7,9(11)-dehydroergosterol and 7,9(11)-bisdehydroporiferasterol], two 5 alpha, 8 alpha-epidioxy-delta(6)-sterols (ergosterol peroxide and 7-dehydroporiferasterol peroxide), and a 7-oxo-delta(5)-sterol (7-oxocholesterol), among others. The delta 5'7-sterols, 5 alpha, 8 alpha-epidioxy-delta(6)-sterols and 7-oxo-delta 5-sterol inhibited TPA-induced inflammation in mice. The 50% inhibitory dose of these compounds for TPA-induced inflammation was 0.2-0.7 mg/ear. Furthermore, ergosterol peroxide markedly inhibited the tumor-promoting effect of TPA in 7,12-dimethylbenz[a]anthracene-initiated mice.

9,10-Dimethyl-1,2-benzanthracene

[Comparative study of the combined effect of HCFU and dipyridamole (DP) in colorectal carcinoma--TS inhibition rate. Kinki Cooperative Study Group of Chemotherapy for Colorectal Carcinoma].

In the forty-seven medical centers in the Kinki district, a comparative trial was conducted to investigate the enhancement of the efficacy of HCEU due to dipyridamol (DP), which is a biochemical modulator in patients with colorectal cancer who have had a curative resection. The trial consisted of two comparative groups: one group (Group A) received HCFU only for five days before operation and for two years from the second week, and the other group (Group B) was given HCFU + DP for the same trial period as Group A. The total number of patients collected was 653 (Group A: 327 patients; Group B: 326 patients) during the two-year trial period from October, 1991. Thymidylate Synthetase (TS) activity in the primary lesions, which is an index of proximity effect, was measured, and the TS inhibition rate (TSIR) was calculated from the activities. The results showed that the TSIR in the primary lesions for the HCFU + DP group (Group B: 0.33) was significantly higher than that of the HCFU group (Group A: 0.27) (p = 0.0006). There was no increase in the side effects of HCFU due to combined administration with DP. From the above results, the therapy with HCFU + DP is expected to be useful for patients with colorectal cancer who have undergone curative resection.

Adult