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Biomedical subjects

H Kanno

Publications and source records attributed to H Kanno.

At least 127 records · Page 7Linked to original sources
PubMed1996

[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↗
PubMed1996

Malignant lymphoma of the adrenal gland: its possible correlation with the Epstein-Barr virus.

Initial manifestation of malignant lymphoma in the adrenal gland is a rare event, and clinical and pathologic features are not fully understood. We conducted a nationwide study in Japan, and 20 patients with malignant lymphoma that showed initial and main manifestation in the adrenal gland were identified. Clinical and pathologic findings were summarized. In addition, the presence of the Epstein-Barr virus (EBV) genome in the tumor cells was examined by using polymerase chain reaction (PCR) and in situ hybridization (ISH), together with the immunohistochemical evaluation of the expression of latent membrane protein-1 (LMP-1). There were 13 men and seven women; their ages at admission ranged from 40 to 87 years (median, 65 yr). Fever, anemia, and elevation of lactic dehydrogenase levels were the common presenting findings. One patient had acquired immunodeficiency syndrome. Adrenal tumors were bilateral in 15 patients and unilateral (all in the left site) in five. Prognosis was very poor; all but two patients died within 1 year after admission. Histologically diffuse large cell type was the commonest type (14 specimens). Immunohistologically, 16 specimens were B-cell type, and one was T-cell type. Another three specimens showing no positive reaction for any antibodies were also judged as B-cell type on purely morphologic grounds. Prominent intravascular proliferation of tumor cells was found in five patients. PCR for EBV genomes gave positive results in five patients; the virus was subtyped as A in three patients and as B in two. The ISH provided positive signals in nine samples, including all five specimens positive for PCR. Four of the nine cases with detectable EBV by PCR and/or ISH expressed LMP-1. The present study shows that adrenal lymphoma is EBV associated and has a B-cell phenotype.

Adrenal Gland Neoplasms↗
PubMed1996

Interleukin-6-mediated growth enhancement of cell lines derived from pyothorax-associated lymphoma.

Malignant lymphomas frequently develop in the pleural cavity of the patients with long-standing pyothorax. Thus, the term pyothorax-associated lymphoma (PAL) has been proposed for this type of tumor. Most PAL are diffuse large cell lymphoma of B cell type that contain Epstein-Barr virus DNA. We have established two lymphoma cell lines from the biopsy specimens of PAL cases, OPL-1 and OPL-2. Because PAL develop in the sites of chronic inflammation, inflammatory cytokines might be involved in the lymphomagenesis. To address this point, we examined the regulation of the growth of OPL by human IL-6. Human recombinant IL-6 enhanced the growth rate of OPL. OPL-1 responded to recombinant IL-6 by growing faster even at concentrations of less than 0.1 ng/ml, whereas OPL-2 required higher concentrations of recombinant IL-6. OPL expressed IL-6 receptor mRNA detectable by reverse transcriptase PCR analysis and IL-6 receptor on cell surface by flow cytometric analysis, using anti-IL-6 receptor antibodies. On the other hand, only OPL-1 showed expression of IL-6 mRNA, which was detectable only by reverse transcriptase PCR, and secreted IL-6 protein into the culture media. The culture supernatant of OPL-1 exhibited growth-enhancing effects on OPL-1 and OPL-2. The addition of anti-IL-6 antibodies to the cultures inhibited the growth of OPL-1 but not OPL-2. OPL-2 did not secrete IL-6 protein into the media, and the culture supernatant from OPL-2 did not enhance growth of OPL-2. These findings suggest the involvement of IL-6 in the growth regulation of OPL, i.e., an autocrine mechanism of IL-6-related proliferation in OPL-1 and a paracrine mechanism in OPL-2. IL-6 locally produced in chronic pyothorax might also promote the development of PAL.

Base Sequence↗
PubMed1996

[Glutathione synthetase deficiency].

CASE REPORT: The patient was a boy born in June, 1990. The proband's father had a history of nonspherocytic hemolytic anemia. The patient was anemic at birth (Hb 11.9 g/dl) and had a hemolytic attack on postnatal day 2. His hemolysis became well compensated, and his second hemolytic episode occurred at three years of age. CLINICAL AND LABORATORY FINDINGS: The patient's mental development had so far been normal and he has no neurological symptoms. His only clinical manifestation has been compensated hemolytic anemia with a hemoglobin concentration of about 11.0 g/dl and a reticulocyte count of 3-6%. He was positive on the Heinz body formation test, and target cells were seen on his peripheral blood smear. The osmotic fragility test yielded slightly increased value. Decreased reduced glutathione (GSH) was observed (4.4 mg/dlRBC) (normal range: 63.9 +/- 9.6), and he also had decreased glutathione synthetase (GS) activity of 0.03 U/gHb (0.38 +/- 0.08 U/gHb). A diagnosis of GS deficiency was made. Decreased glutathione S-transferase (GST) activity was also found (0.57 U/gHb) (normal range: 6.65 +/- 1.20). DISCUSSION: GS deficiency has been reported in about 30 families all over the world. This patient was the first Japanese patient with red cell GS deficiency.

Child↗
PubMed1996

[Molecular basis and pathophysiology of red cell enzymopathies].

Recent progress in the molecular analysis of red cell enzymopathies showed over 160 mutations in the 10 distinct genes which were essential in red cell metabolisms. In addition, since three-dimensional structure of several enzymes including pyruvate kinase (PK) and glucose-6-phosphate dehydrogenase (G6PD) have been elucidated from X-ray crystallographic studies, the effect of amino acid substitutions on enzyme activity became predictable in some extent. On the contrary, the mechanism of hemolysis remains still unclear. To clarify the pathophysiology of red cell enzymopathies, establishment of an animal model have been long awaited. Recently we discovered the novel mice model of PK deficiency. The mutant mice with splenomegaly and nonspherocytic hemolytic anemia in an inbred colony of the CBA strain were enzymatically diagnosed as PK deficiency. A homozygous missense mutation was identified in the red cell (R)-type PKcDNA sequence of the mutant, and it caused a single amino acid substitution near the substrate binding site of PK. The erythroid-progenitor cell number increased in spleen of the mutant mice to a level approximately 66 times higher than in normal CBA mice, suggesting that compensatory extramedullary erythropoiesis in the spleen of the mutant mice might partly compensate the anemia. The mutant mice will be useful as an experimental model for understanding the pathophysiology of this disorder.

Animals↗
PubMed1996

[Clinical studies on vancomycin in the treatment of MRSA infection].

We evaluated the effectiveness and safety of vancomycin (VCM) alone and in combination with beta-lactam antibiotics in the treatment of MRSA infections, and obtained the following results: 1. Effectiveness. (1) In cases of MRSA infections alone, the improvement rate was 71.4% (5/7 patients) with VCM alone and 77.8% (35/45) with VCM in combination with beta-lactam antibiotics. (2) In cases of polymicrobial infections, few cases were treated with VCM alone, but the improvement rate in combination use with beta-lactam antibiotics was 71.8% (28/39). 2. Bacteriological effect. (1) In cases of single infection with MRSA, the rate of bacterial eradication was 71.4% (5/7) with VCM alone and 68.2% (30/44) with VCM in combination with beta-lactam antibiotics. (2) In cases of polymicrobial infections, few cases were treated with VCM alone, but the rate of bacterial eradication in combination use with be ta-lactam antibiotics was 63.2% (24/38) against MRSA and 31.6% (12/38) against polymicrobial agents including MRSA. 3. Safety. Occurrences of adverse reactions and abnormal laboratory test values when VCM was used alone or when it is used in combination with another drug were about the same in these uses. As a whole, advance reactions were observed in 16 patients (9.5%). Main adverse reactions were whole body redness, drug eruption, and rash etc. Abnormal laboratory test values were observed mainly in hepatic functions, and renal functions. 4. VCM concentrations in blood was determined in 38 patients. Doses of 0.5 g and 1.0 g of VCM was administered by intravenous drip infusion over a period of 1 to 2 hours, and mean blood concentrations 1 to 2 hours after the completion of drip infusion were 25.4 micrograms/ml and 14.4 micrograms/ml, respectively. 5. Synergic effects between VCM and other antibiotics tested were observed in FIC index against all of the six MRSA strains isolated from six patients, and the clinical effects of improvement or better were obtained against five of them.

Adolescent↗
PubMed1995

Pyruvate kinase deficiency of mice associated with nonspherocytic hemolytic anemia and cure of the anemia by marrow transplantation without host irradiation.

Mutant mice with splenomegaly and nonspherocytic hemolytic anemia were found in an inbred colony of the CBA/N (hereafter CBA) strain maintained in the Japan SLC Haruno farm (Shuchi-gun, Shizuoka, Japan). The activity of pyruvate kinase (PK) in red blood cells (RBCs) of the anemic mutants decreased to 16.2% of normal (+/+) CBA mice. Because the mutant CBA mice showed a remarkable reticulocytosis (41.6%) and because the PK activity of reticulocytes is much higher than that of mature RBCs, the PK activity in mature RBCs of the mutant CBA mice was calculated to be 2.8% that of mature RBCs of CBA-(+/+) mice. Because RBC type PK is encoded by the Pk-1 locus of the mouse (chromosome 3), we designated the mutant locus as Pk-1slc. The anemia and PK deficiency of CBA-Pk-1slc/Pk-1slc mice were cured by bone marrow transplantation (BMT) from CBA-(+/+) mice. Prior irradiation was not necessary for the curative BMT. On the other hand, the BMT from CBA-Pk-1slc/Pk-1slc mice to nonirradiated CBA-(+/+) mice did not result in the decrease of RBCs and the reduction of PK activity. The present results indicate that CBA-Pk-1slc/Pk-1slc mice are a potentially useful animal model for studying pathophysiology of PK deficiency and for developing new therapeutic methods to correct PK deficiency.

Anemia, Hemolytic, Congenital Nonspherocytic↗
PubMed1995

Primary structure of murine red blood cell-type pyruvate kinase (PK) and molecular characterization of PK deficiency identified in the CBA strain.

To clarify the molecular abnormality of pyruvate kinase (PK) deficiency identified in the mutant mice of CBA-Pk-1slc/Pk-1slc, we cloned murine red blood cell-type PK (R-PK) cDNA of those animals. The cDNA sequence spans 1827 bp, including an open reading frame that can encode 574 amino acids. Homology in the coding sequences between murine and human R-PK was 86.1% at nucleotide and 91.5% at amino acid levels. A homozygous missense mutation at nucleotide 1013 GGT-->GAT was identified in the cDNA sequence of the mutant, causing a single amino acid substitution at no. 338Gly-->Asp of the murine R-PK. Six amino acid residues, 335Val-336Ala-337Arg-338Gly-339Asp-340L eu, were encoded in exon 8 of both human and rat L (liver-type)/R-PK genes and were evolutionarily conserved in PK from bacteria through humans. 337Arg was reported to be important for substrate binding, suggesting that the amino acid change would impair substrate affinity of the PK subunit. A homozygous missense mutation at the catalytic domain has been identified in a human PK variant, PK Hong Kong (941ATT-->ACT, 314 Ile-->Thr). Although both 1013A and 941C gave rise to an amino acid change adjacent to the active site and may interfere with substrate binding to the subunit, the degree of anemia was much more severe in the human case. The erythroid-progenitor cell number increased in the spleen of Pk-1slc/Pk-1slc mice to a level approximately 66 times higher than that in normal CBA mice, suggesting that compensatory extramedullary erythropoiesis in the spleen of the mutant mice, but not in the human variant, might account for the observed difference in the phenotype.

Amino Acid Sequence↗
PubMed1995

Use of immunohistochemical procedures in diagnosing angiosarcoma. Evaluation of 98 cases.

BACKGROUND: Differential diagnosis of angiosarcoma, predominantly showing a non- or poorly vasoformative proliferation from other types of sarcomas, poorly differentiated carcinomas, and amelanotic melanoma, is often problematic. METHODS: The use of antibodies directed against Factor VIII-related antigen (FVIIIRA), Ulex europaeus lectin type 1 (UEA-1), CD31, and vascular endothelial growth factor (VEGF) in the diagnosis of angiosarcoma was examined in 98 cases of autopsy-proven angiosarcoma diagnosed during 1974-1990 in a survey of 178 Japanese hospitals. Reactivity of angiosarcoma cells for epithelial membrane antigen, cytokeratin, and melanoma cell antigen (HMB45) also was examined. RESULTS: Histologic specimens were formed exclusively by vasoformative areas in 32 cases and combined vasoformative and varying extents of non- or poorly vasoformative areas in another 66 cases. In vasoformative areas, the proliferating cells showed a diffuse positive reaction in the cytoplasm and/or cell surface for anti-FVII-IRA in 82 (84%) of 98 cases, for anti-CD31 in 78 (80%), and for UEA-1 in 69 (70%). In non- or poorly vasoformative areas, the positivity rate for FVIIIRA, CD31, and UEA-1 was 29%, 62%, and 46%, respectively. A positive reaction was found for either one of three endothelial markers in the non- or poorly vasoformative areas of 57 cases (86%). Epithelial membrane antigen and anticytokeratin antibody were positive in 4 and 11 cases, respectively, in the vasoformative areas and in 3 and 14 cases, respectively, in non- or poorly vasoformative areas with a simultaneous positive reaction for either one of three endothelial cell markers. None of the proliferating cells showed a positive reactivity for HMB45. The positivity rates of the angiosarcoma cells for each marker were different according to the primary tumor sites. The angiosarcoma cells in non- or poorly vasoformative areas showed the lowest positivity rate for anti-FVIIIRA in the heart (9%) and for anti-CD31 in the extremities (17%) and the highest positivity rate for anticytokeratin in the trunk (60%). Ulex europaeus lectin type 1 had almost the same reactivity rate (30-56%) in every organ. Angiosarcoma cells in 13 (36%) of 36 biopsy specimens and 8 (14%) of 56 autopsy specimens were positive for the anti-VEGF antibody. CONCLUSION: These findings suggest that the combined use of endothelial cell markers including FVIIIRA, UEA-1, and CD31 is useful in the diagnosis of angiosarcoma, especially in cases exclusively with a non- or poorly vasoformative pattern.

Adolescent↗
PubMed1995

Angiosarcoma in Japan. A review of 99 cases.

BACKGROUND: Angiosarcoma is rare, and information about its clinical features are limited. Therefore, a large scale study of angiosarcoma was performed in Japan. METHODS: Through a nationwide Japanese study, 99 cases of angiosarcoma were collected and their clinicopathologic findings were summarized relative to predisposing risk factors. RESULTS: The patient age at diagnosis was 3-92 years, (mean, 62 years), with a two to one male to female ratio. The head and face were the most common primary site (29 cases); other sites were liver (17); trunk (13): pleural cavity (6), chest wall (2), abdominal wall (2), buttock (2), inguinal region (1); heart (12); and extremities (7). The proven predisposing risk factors included chronic pyothorax for angiosarcoma in the pleural cavity (six), thorotrast in the liver (five), radiotherapy to the abdominal wall and buttock (four), and chronic limb edema of the forearm (one). Irrespective of primary sites, the majority of cases had metastases to lung in 72 cases, bone in 42, liver in 36, regional lymph nodes in 30, and adrenal gland in 24. The 2-year survival rate was 17%. CONCLUSIONS: This study describes a different etiology in the development of angiosarcoma in patients from Japan compared with that of patients from Western countries, though the frequency of angiosarcoma among all soft-tissue sarcomas was similar in both areas. In Japan, chronic pyothorax, radiotherapy, and thorotrast proved to be distinctive causative factors of angiosarcoma.

Adolescent↗
PubMed1995

A novel human catalase mutation (358 T-->del) causing Japanese-type acatalasemia.

Japanese-type acatalasemia is characterized by the almost total loss of catalase activity in red cells and is often associated with ulcerating oral lesions. A splicing mutation in intron 4 of catalase gene has so far been a sole disease-causing mutation found in Japanese-type acatalasemic patients. We report here a novel single base deletion in the catalase gene causing Japanese-type acatalasemia. The patient was a 72 year-old Japanese male. His maternal grandmother and his father were first cousins. Molecular analysis using non-RI PCR-SSCP analysis combined with direct sequencing revealed a deletion of the 358th thymine in exon 4 of the patient's catalase gene. The proband was a homozygote and his mother and his three children were heterozygotes for this mutation. The frame shift caused by the nucleotide deletion should alter the downstream amino acid sequence and introduce a new termination codon TGA 43 bp 3' to the mutation. Although the truncated peptide chain consisted of 133 amino acid residues might be translated in the patient's tissue, such an aberrant protein is expected to be extremely unstable and have no catalytic function at all. Our results suggest that Japanese-type acatalasemia is heterogeneous.

Acatalasia↗
PubMed1995

Cochlear effects of indacrinone are not altered by penicillin.

Indacrinone is a loop diuretic structurally related to ethacrynic acid. Indacrinone is a racemic mixture. Previous studies have shown that the (-) enantiomer caused reduction of endocochlear potential (EP) and elevation of compound action potential (CAP) threshold (Rybak and Whitworth, 1987a). It has been demonstrated that organic acids such as penicillin, probenecid and sodium salicylate prevent the reduction of EP normally observed after furosemide administration (Rybak et al., 1992a). The present study was designed to determine whether penicillin pretreatment could prevent changes in EP and CAP threshold in (-)-indacrinone treated chinchillas. Adult chinchillas were anesthetized with ketamine and pentobarbital. A microelectrode was advanced into the scala media using the round window approach, and CAP responses to clicks were measured. One group was treated with (-)-indacrinone 100 mg/kg via the jugular vein. A second group of animals received penicillin 50 mg/kg i.v. thirty minutes before (-)-indacrinone. The mean EP change in the indacrinone-treated animals was 38.38 +/- 19.32 millivolts (mv). The reduction of EP in the group receiving penicillin was 24.43 +/- 20.74 mv (P > 0.09). The mean CAP threshold changes in animals receiving indacrinone was 20 +/- 14.14 dB whereas those pretreated with penicillin showed a threshold shift of 21.43 +/- 20.35 dB (P > 0.05). These findings are consistent with previous studies which showed that the effect of ethacrynic acid on the EP and CAP was not changed by the pretreatment with penicillin (Rybak et al., 1990).

Action Potentials↗
PubMed1995

Immunological detection of penicillin-binding protein 2' of methicillin-resistant staphylococci by using monoclonal antibodies prepared from synthetic peptides.

Two synthetic peptides 31 and 32 amino acids in length were prepared as deduced from a known amino acid sequence of penicillin-binding protein 2' (PBP2') of methicillin-resistant Staphylococcus aureus. Two monoclonal antibodies were generated from fused cells of myeloma cells and splenic cells of mice immunized with the synthetic peptides. Western blot (immunoblot) analysis demonstrated specific binding of the antibodies to PBP2' of a methicillin-resistant S. aureus strain. An immunoradiometric assay was developed by using these antibodies for simple detection of PBP2'.

Amino Acid Sequence↗
PubMed1995

Sporadic activation of Epstein-Barr virus in thyroid lymphoma.

The causal role of Epstein-Barr virus (EBV) in the development of B-cell lymphoma, especially in immunocompromised individuals, has been suggested. The purpose of the present study was to evaluate an association of EBV with thyroid lymphoma (TL) and chronic lymphocytic thyroiditis (CLTH) which is known to play an important role in the development of TL. Thirty cases with TL and 28 with CLTH were studied for presence or absence of EBV genome in the lesions using the polymerase chain reaction (PCR) and the in situ hybridization method. EBV genomes were detected by PCR in one and two cases with CLTH and TL, respectively. Subtyping of EBV genome was possible in one TL case showing B-type in EBNA-2 coding region. In situ hybridization revealed positive signals in the nucleus of lymphoma cells, which also expressed latent membrane protein-1. The present findings indicate that activation of EBV in TL is not common.

Adolescent↗
PubMed1995

[Effect of caffeine and pentoxifylline on human sperm motility after one week storage at 3 degrees C].

The effect of caffeine (C) and pentoxifylline (P) on the sperm motility was examined after a 3 degrees C storage in a TEST yolk buffer for one week. Thus stored 24 semen samples from infertile patients were incubated with or without C or P at 37 degrees C. The motility was analysed for up to 240 minutes. The poststorage addition of C (1 mM) and P (1 mM) significantly increased the serum motility rate (p < 0.01). The stimulant effect of C and P was rather transient lasting no more than 2 hours. The prestorage addition of C and P in a preservant TEST yolk buffer was less effective than the poststorage administration. According to the time-related profiles of the sperm motility, 24 cases were divided into three groups. In group A (11 cases), the sperm motility rate increased from 30 to 90 minutes even without C or P. This group was responder of C and P. In group B (8 cases), the motility rate increased only in response to C and P and, in group C (5 cases), no such responses were observed. The prestorage semen qualities in terms of the sperm concentration, the motility rate, the velocity, the linearity, and the amplitude of the lateral head displacement were compared in these three groups. There was a significant difference between these 3 groups (p < 0.05) on the parameters in terms of the sperm concentration, motility rate and velocity. It was suggested that these prestorage parameters predict the sperm activity in response to C and P after a one week 3 degrees C storage.

Adult↗
PubMed1995

[Results of mutation analyses of von Hippel-Lindau disease gene in Japanese patients: comparison with results in United States and United Kingdom].

Recently the gene responsible for the von Hippel-Lindau (VHL) disease was identified as a tumor suppressor gene. Our ongoing studies on the mutation of the VHL gene in Japanese 28 VHL families with single strand conformational analyses of DNA and Southern blot analyses revealed 6 cases of insertion or deletion, 1 cases of splice site mutation and 9 cases of missense mutation, and 3 possible intragenic deletions. Our analytical findings are essentially similar to those observed in the western countries. The VHL families associated with pheochromocytoma had the same mutational hot spot as those in the western countries. Molecular analyses of the VHL gene in the Japanese VHL disease substantially improved the understanding of this disease and its inheritance character.

Blotting, Southern↗
PubMed1995

[Pyruvate kinase (PK) isozyme switching and genetic heterogeneity of PK deficiency].

Pyruvate kinase (PK) is a key glycolytic enzyme and has two structural genes; the L/R-gene encodes the L- and R-type PK, whereas the M-gene encodes the M1- and M2-type isozymes. The isozyme switches from the M2 to the R-type during erythroid differentiation, and recent results showed that the switching was achieved by activation of the R-PK promoter activity and the involvement of erythroid-specific transcription factors has been demonstrated. Glycolysis is a major energy source for red cells, therefore, PK deficiency results in hemolysis. PK deficiency is the most common glycolytic enzyme defect associated with hereditary hemolytic anemia, and inherited in an autosomal recessive manner. To date, 46 gene mutations have been identified, and molecular approach might be helpful for diagnosis of PK deficiency, particularly among transfusion-dependent subjects or infantile cases.

Anemia, Hemolytic↗