[A case of mesenchymal chondrosarcoma in the orbit].
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Adult↗
Biomedical subjects
H Kanno
Publications and source records attributed to H Kanno.
Low substrate affinity of pyruvate kinase variant (PK Sapporo) caused by a single amino acid substitution (426 Arg-->Gln) associated with hereditary hemolytic anemia.
A point mutation (1277 CGG to CAG) was identified in the R-type pyruvate kinase (PK) cDNA of a PK variant, PK Sapporo, associated with hereditary non-spherocytic hemolytic anemia. The mutation causes a single amino acid substitution from Arg to Gln at the 426th amino acid residue of human R-type PK; consequently, the hydrophobicity around the mutated site is drastically decreased. The amino acid change occurred in the eighth alpha helix of A domain (A alpha 8) of PK, and it has been proposed that this region as well as A alpha 7, A beta 7, and A beta 8 is a potassium (K+) binding site. Because K+ binding to the PK subunit is considered to be essential for substrate binding, the mutation might account for the decreased affinity for phosphoenolpyruvate (PEP). This is compatible with the fact that all the reported PK variants carrying point mutations in those area have a high Michaelis constant (Km) for PEP.
Amino Acid Sequence↗
Molecular basis of impaired pyruvate kinase isozyme conversion in erythroid cells: a single amino acid substitution near the active site and decreased mRNA content of the R-type PK.
Conversion of pyruvate kinase (PK) isozymes from M2- to R-PK has been observed during erythroid cell maturation. To understand this mechanism, we analyzed the PK gene of a R-PK deficient patient, in whose erythrocytes the M2-PK was persistently expressed. A point mutation, 1102 GTC-->TTC was identified in the R-PK cDNA, and it caused a single amino acid substitution from 368Val-->Phe. The residue is very close to the 372nd Gln, the putative binding site of the monovalent cation (K+). The impaired K+ binding would cause the decreased affinity for phosphoenolpyruvate, consequently the variant PK may be extremely unstable. Although the proband's other PK allele did not have any structural change, the R-PK mRNA level in reticulocytes was decreased. These findings suggested that both the structural mutation near the active site and the decreased mRNA level of the R-PK were responsible for the disorder.
Amino Acid Sequence↗
The influence of docosahexaenoic acid loading on stroke-prone spontaneously hypertensive rats.
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Animals↗
Concise review: pyruvate kinase deficiency: historical perspective and recent progress of molecular genetics.
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Animals↗
A case of fatal infectious mononucleosis presenting with fulminant hepatic failure associated with an extensive CD8-positive lymphocyte infiltration in the liver.
We describe a fatal case of infectious mononucleosis presenting with fulminant hepatic failure associated with extensive CD8-positive lymphocyte infiltration and diffuse karyorrhexis in the liver. Immunohistochemical analysis of mononuclear cells showed that Leu-2a (CD8)-positive lymphocytes were heavily distributed in the portal areas and the sinusoidal spaces, but Leu-3a (CD4)-, Leu-14 (CD22)-, or My 4 (CD14)-positive cells were undetectable in sections of the liver. Southern blot hybridization studies disclosed the presence of Epstein-Barr virus DNA fragments in the liver tissue. The unusual pathologic and immunologic responses observed in this case could not simply be explained by severe Epstein-Barr virus infection. Some superimposed factors should be considered.
CD8 Antigens↗
Relationship between aromatase activity and steroid receptor levels in ovarian tumors from postmenopausal women.
Aromatase activity, as well as steroid receptors, exists in nonfunctional ovarian tumors. Steroid receptor status has been reported to be related to prognosis in ovarian cancer patients. We determined aromatase activity and progesterone receptor (PR) and estrogen receptor (ER) levels in 43 ovarian tumors obtained from postmenopausal women. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%). Eighty-three percent (10/12) of mucinous cystadenoma tissues showed positive PR with high aromatase activity, while 93% (13/14) of malignant tumors showed negative PR and low aromatase activity. Aromatase activity was detected in 95% (20/21) of PR-positive tumors, being greater than in PR-negative tumors (P < 0.002). There was a positive correlation between aromatase activity and PR (rs = 0.49, P < 0.001). However, there was no correlation between aromatase activity and ER. In 17 patients (43%), the serum estradiol level was higher than 30 pg/ml and there was a positive correlation among estradiol, estrone, androstenedione and testosterone. However, serum steroid levels were not correlated with aromatase activity, PR or ER. Aminoglutethimide inhibited aromatase activity of benign and malignant ovarian tumors, uterine myoma, choriocarcinoma cells and purified human placental P-450arom in a similar manner. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women. In addition to steroid receptor status, aromatase activity may be a useful prognostic factor in ovarian cancers.
Adult↗
Growth suppression of MCF-7 human breast cancer cells by aromatase inhibitors: a new system for aromatase inhibitor screening.
In our previous study we found that MCF-7 cells possess aromatase activity and stimulate estrogen receptor-mediated growth. The pathways through which androgens are converted to estrogens by aromatase and estrogens interact with estrogen receptors contribute significantly to growth stimulation. The administration of aromatase inhibitor results in suppression of growth stimulation by androgens. This system enabled us to assess directly the biological activities of aromatase inhibitors. Aromatase activity was inhibited in a dose-dependent manner by the addition of aminoglutethimide and CGS 16949A, competitive inhibitors, and of 14 alpha-hydroxy-4-androstene-3,6,17-trione and 4-hydroxy-androstenedione, mechanism-based inhibitors. After preincubation with mechanism-based inhibitors, aromatase activity was significantly suppressed, whereas after preincubation with competitive inhibitors, it was adversely increased. These effects were concentration- and time-dependent. Preincubation with competitive inhibitors resulted in augmentation of subsequent androgen stimulation of thymidine incorporation, while preincubation with mechanism-based inhibitors resulted in diminished stimulation by subsequent androgen administration. These results suggest that in MCF-7 cells competitive inhibitors adversely induce aromatase and accelerate the subsequent androgen stimulation of DNA synthesis. Suicide inhibitors are more effective than competitive inhibitors. This system will be useful for aromatase inhibitor screening.
Aminoglutethimide↗
5' structure and expression of human glucose-6-phosphate dehydrogenase mRNA.
The human glucose-6-phosphate (G6PD) cDNAs cloned from normal and carcinoma cells can encode 545-amino-acid residues starting from the first in-frame chain initiation codon. However, it was reported that the G6PD mRNAs of carcinoma cell lines were shorter and could encode only 515-amino-acid residues (Martini et al., 1986). We demonstrated the existence of two major G6PD mRNAs in normal reticulocytes, lymphoblasts, and hepatocytes by the primer extension analysis. The longer mRNA has a cap site at approx. nucleotide -166 and can encode 545-amino-acid residues, whereas the shorter mRNA has a cap site at approx. nucleotide -66, and encodes 515-amino-acid residues. These two naturally existing mRNAs (cDNAs) and an artificially truncated mRNA, which can encode the carboxy-terminal 479-amino-acid residues of the subunit, were expressed in the in vitro reticulocyte and wheat germ systems and in the in vivo E. coli system. All three species of mRNA (cDNA) were efficiently translated and produced proteins with the expected molecular sizes. The peptide with 515 residues formed the catalytically active enzyme, but the 545-residue protein and the 479-residue protein were catalytically inactive. The larger 545-residue protein may correspond to the larger G6PD precursor observed in the rat. The extended amino-terminal region encoded by the larger mRNA contains the -Arg-Gly-Gly-Arg-Arg-Arg-Arg-sequence, which is conserved in the nucleotide-binding protamine family.
Amino Acid Sequence↗
Aleutian mink disease parvovirus infection of mink macrophages and human macrophage cell line U937: demonstration of antibody-dependent enhancement of infection.
Aleutian mink disease parvovirus (ADV) infects macrophages in adult mink. The virulent ADV-Utah I strain, but not the cell culture-adapted ADV-G strain, infects mink peritoneal macrophage cultures and the human macrophage cell line U937 in vitro. However, preincubation of ADV-G with ADV-infected mink serum enhanced its infectivity for U937 cells. the enhancing activity was present in the protein A-binding immunoglobulin G fraction in the serum, but F(ab')2 fragments failed to enhance the infection. On the other hand, the same sera inhibited ADV-G infection of Crandell feline kidney (CRFK) cells. Although U937 cells were not fully permissive for antibody-enhanced ADV-G infection, ADV mRNA expression, genome amplification, and protein expression were identical to those found previously for ADV-Utah I infection of U937 cells. Preincubation of ADV-Utah I with soluble protein A partly inhibited the infection of U937 cells but did not affect infection of CRFK cells. In mink peritoneal macrophages, preincubation with the infected mink serum did not make ADV-G infectious. However, the infectivity for mink macrophages of antibody-free ADV-Utah I prepared from the lungs of infected newborn mink kits was enhanced by ADV-infected mink serum. Moreover, protein A partly blocked ADV-Utah I infection of mink macrophage cultures. These results suggested that ADV-Utah I enters mink macrophages and U937 cells via an Fc receptor-mediated mechanism. This mechanism, antibody-dependent enhancement, may also contribute to ADV infection in vivo. Furthermore, since ADV infection in mink is characterized by overproduction of anti-ADV immunoglobulins, antibody-dependent enhancement may play a critical role in the establishment of persistent infection with ADV in vivo.
Aleutian Mink Disease Virus↗
Aleutian mink disease parvovirus infection of mink peritoneal macrophages and human macrophage cell lines.
Aleutian mink disease parvovirus (ADV) mRNAs are found in macrophages in lymph nodes and peritoneal exudate cells from ADV-infected mink. Therefore, we developed an in vitro infection system for ADV by using primary cultures of mink macrophages or macrophage cell lines. In peritoneal macrophage cultures from adult mink, virulent ADV-Utah I strain showed nuclear expression of viral antigens with fluorescein isothiocyanate-labeled ADV-infected mink serum, but delineation of specific viral proteins could not be confirmed by immunoblot analysis. Amplification of ADV DNA and production of replicative-form DNA were observed in mink macrophages by Southern blot analysis; however, virus could not be serially propagated. The human macrophage cell line U937 exhibited clear nuclear expression of viral antigens after infection with ADV-Utah I but not with tissue culture-adapted ADV-G. In U937 cells, ADV-Utah I produced mRNA, replicative-form DNA, virion DNA, and structural and nonstructural proteins; however, virus could not be serially passaged nor could [3H]thymidine-labeled virions be observed by density gradient analysis. These findings indicated that ADV-Utah I infection in U937 cells was not fully permissive and that there is another restricted step between gene amplification and/or viral protein expression and production of infectious virions. Treatment with the macrophage activator phorbol 12-myristate 13-acetate after adsorption of virus reduced the frequency of ADV-positive U937 cells but clearly increased that of human macrophage line THP-1 cells. These results suggested that ADV replication may depend on conditions influenced by the differentiation state of macrophages. U937 cells may be useful as an in vitro model system for the analysis of the immune disorder caused by ADV infection of macrophages.
Aleutian Mink Disease Virus↗
A macrophage differentiating factor derived from human T cell line HUT102 acting on a mouse myeloid cell line M1.
Human T cell leukemia virus type I-transformed T cell line HUT102 constitutively secreted soluble factors which induced differentiation of a murine myeloid leukemic cell line, M1, to increase the immune complex-binding and/or phagocytizing capacity. This macrophage differentiating factor(s) (MDF) was purified from the culture supernatants of HUT102 cells by using several steps of column chromatography and novel immune-adherence and/or immune-phagocytic assays. The finally purified MDF activity was detected in the fraction that consisted of 40,000- and 45,000- molecular weight molecules. Antibodies specific for human interleukin-6 or for human granulocyte-colony stimulating factor, both of which have differentiation-inducing activity on M1 cells when used as a single factor, could not neutralize the MDF activity. These findings suggest that the 40,000- and/or 45,000- molecular weight molecules in the HUT102 cell products may be possible novel differentiation-inducing factors acting on a murine macrophage lineage across the species barrier.
Animals↗
The effect of endocochlear potential suppression upon susceptibility to acoustic trauma.
In the present study we investigated the influence of decreased endocochlear potential (EP) on acoustic trauma. Guinea pigs with decreased EP following i.v. administration of furosemide (FUR) and normal EP given physiological saline solution (PSS) i.v. instead of FUR were exposed to 2 kHz pure tone ranging from 110 to 130 dB SPL for 5 min. The input-output curves of the compound action potential (CAP) before acoustic overstimulation were compared with those at 2 h after the exposure. In 125 and 130 dB SPL exposure there was no difference in threshold shift between the FUR and PSS groups. In 115 and 120 dB SPL exposure, however, the threshold shift of the FUR group was significantly smaller than that of the PSS group. There was no significant difference between the two groups in 110 dB SPL exposure. These results indicate that the threshold shift of the CAP is mainly due to excessive vibration of the basilar membrane in the greater stimulus groups (125-130 dB SPL) but that the energy exhaustion of the hair cells to a certain extent participates in the threshold shift when the stimulus is milder (115-120 dB SPL). It is concluded that susceptibility to acoustic trauma of a milder intensity (115-120 dB SPL) is reduced when the energy consumption rate of the organ of Corti is decreased by EP suppression.
Acoustic Stimulation↗
Urinary epidermal growth factor in patients with gliomas: significance of the factor as a glial tumor marker.
Epidermal growth factor (EGF) content in urine from patients with glial tumors was examined by radioimmunoassay techniques with labeled human EGF and its rabbit EGF polyclonal antibody. There was no cross-reaction with transforming growth factor-alpha, which has a common receptor with EGF. Forty glial tumors were divided into three groups according to the clinical stage: Samples from Group A patients were obtained before therapy and/or after biopsy; in these patients a large volume of tumor was apparent on computerized tomography (CT). Group B samples were obtained after gross total removal of the tumor and/or chemo- and radiation therapy; these patients showed a small volume of residual tumor on CT. Samples from Group C patients were obtained after gross tumor total removal and/or chemo- and radiation therapy; no tumor was detected on CT scans in these patients. Urinary EGF levels in Group A samples were statistically significantly higher than in samples from healthy individuals (p < 0.001), Group B patients (p < 0.10), and Group C patients (p < 0.02). In addition, high-grade glial tumors in Group A cases showed a significantly higher level of urinary EGF than low-grade tumors in Group A patients (p < 0.05), or patients with meningioma (p < 0.02), metastatic brain tumor (p < 0.05), and cerebral infarction (p < 0.001). Longitudinal changes of urinary EGF levels in glioma patients mostly synchronized with the clinical course and therapeutic interventions. Therefore, urinary EGF, as a glial tumor marker, may be of practical value for diagnosing a malignant glioma and evaluating for the efficacy of chemo- and radiation therapy.
Adolescent↗
[Relationship among aromatase activity, estrogen receptor and progesterone receptor in ovarian tumors from postmenopausal women].
Aromatase activity, as well as steroid receptors, has been demonstrated in ovarian tumors. Aromatase activity was detected in 35 tumors (81%), PR in 21 tumors (49%) and ER in 13 tumors (30%) out of 43 ovarian tumors (27 benign, 14 malignant and 2 granulosa cell tumors). Moreover, immunohistochemical study demonstrated aromatase cytochrome P-450 (P-450arom) in the tumor tissues. Aromatase activity was significantly greater in PR-positive tumors than in PR-negative tumors (p < 0.002). There was a positive correlation between aromatase activity and the PR level (rs = 0.490, p < 0.001). Thirteen of 14 (93%) malignant tumors showed negative PR with low aromatase activity. However, the presence of ER was not correlated with aromatase activity or the presence of PR. There was a positive correlation among serum levels of estradiol, estrone, androstenedione and testosterone, whereas the serum steroid levels were not correlated with aromatase activity, the PR or ER of ovarian tumors. These results suggest that aromatase activity is correlated with PR in ovarian tumors of postmenopausal women.
Adult↗
[Successful management for advanced renal cell carcinoma under combination therapy with human lymphoblastoid interferon-alpha and UFT (mixture of tegafur and uracil): a case report].
We report a case of renal cell carcinoma in a 76-year-old man with pulmonary metastasis and tumor thrombus in inferior vena cava. The patient responded to the combination therapy with a small amount of HLBI (human lymphoblastoid interferon-alpha) and UFT (1:4 mixture of tegafur and uracil). HLBI was administered intramuscularly at a dose of 3 x 10(6) IU two times a week. However, the administration of the same dose was discontinued, because of the severe side effects, such as depression, general fatigue, anorexia and high fever. Finally, the maximum dose was determined to be 2 x 10(6) IU/week. Nine weeks after the first treatment, UFT was simultaneously given orally at a dose of 100 mg/day for potentiating the antitumor effect. At 12 weeks, the patient registered complete response of pulmonary metastasis, and partial response (83% reduction) of renal tumor. About 60 x 10(6) IU HLBI was administered until the response was noted. After 34 weeks of administration of HLBI, nephrectomy was performed. Histological diagnosis was renal cell carcinoma of clear cell subtype, grade 2. Microscopically, many lymphocytes infiltrated into the cancer cells. This suggests the possibility of immunological response caused by HLBI.
Aged↗
Structural analysis of human pyruvate kinase L-gene and identification of the promoter activity in erythroid cells.
The human pyruvate kinase (PK) L-gene is organized in 12 exons over 9.5 kilobases, and the first and second exons are specifically transcribed to the R- and L-type PK mRNA. The 5'-flanking region upstream the first exon has two CAC boxes and four GATA motifs within 250 bp from the translational initiation codon. Comparison with the rat L-gene revealed four well-conserved elements in the region. The transient transfection demonstrated that the 270-bp upstream region was a powerful promoter in K562 cells, whereas deletion of the distal 150-bp sequences, which included three GATA motifs, resulted in drastic reduction of the activity. When the hypersensitive site 2 of the human beta-globin gene locus was joined to the promoter, the activity of the proximal 120-bp region was enhanced. We concluded that the proximal 120-bp region had a basal promoter activity and that the distal 150-bp region acted as an enhancer in erythroid cells.
Animals↗
A single amino acid substitution (157 Gly----Val) in a phosphoglycerate kinase variant (PGK Shizuoka) associated with chronic hemolysis and myoglobinuria.
We have determined a single amino acid substitution in a new phosphoglycerate kinase (PGK) variant, PGK Shizuoka, associated with chronic hemolysis and myoglobinuria. PGK Shizuoka had an extremely low enzyme activity with normal kinetic properties and normal electrophoretic mobility. Total blood cell RNA of the patient was reverse-transcribed and amplified by the polymerase chain reaction. A single nucleotide substitution from guanine to thymine at position 473 of PGK messenger RNA was found. This nucleotide change causes a single amino acid substitution from Gly to Val at the 157th position, which is located in the NH2-terminal domain of the enzyme. This mutation creates a new Bst XI cleavage site in exon 5, and we thus confirmed the mutation in the variant gene. The replacement of Gly by Val is considered to affect enzyme catalysis.
Adult↗