Molecular analysis of new Japanese patients with holocarboxylase synthetase deficiency.
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Biotin↗
Biomedical subjects
Y Aoki
Publications and source records attributed to Y Aoki.
Hepatocyte growth factor stimulates the invasion of gallbladder carcinoma cell lines in vitro.
Human gallbladder cancer is highly malignant and its prognosis is usually poor depending on the extent of surrounding tissue invasion. We examined in vitro the invasive activity of four gallbladder cancer cell lines (GB-d1, GB-h3, GB-d2 and FU-GBC-1) in the absence or presence of hepatocyte growth factor (HGF). In type 1 collagen gel culture, HGF stimulated cell proliferation and induced an invasive phenotype of arborizing structures in GB-d1, GB-h3 and GB-d2. In a Matrigel invasion assay, invasion was also induced in three of these cell lines by HGF but not in FU-GBC-1. Cellular motility was, however, stimulated by HGF in all of the four cell lines to various extents. Zymography for proteolytic enzymes demonstrated high levels of type IV collagenase and urokinase-type plasminogen activator (u-PA) activity in GB-d1, GB-h3 and GB-d2 even in the absence of HGF. In the presence of HGF, the 72 kDa type IV collagenase (MMP-2) activity of GB-h3 and u-PA activities of GB-d1, GB-h3 and GB-d2 were enhanced. In contrast, the MMPs and PAs activities of FU-GBC-1 were faint irrespective of the addition of HGF. A Western blot analysis demonstrated higher levels of 190 kDa c-MET product (HGF receptor) of GB-d1, GB-h3 and GB-d2 than that of FU-GBC-1. The invasion in the Matrigel assay stimulated by HGF was inhibited by protease inhibitors, aprotinin and FOY-305, as well as by anti-HGF antibody. These results thus suggest that, in addition to the importance of the proteolytic activity, the cellular motility induced via the HGF/HGF-receptor system is essential for the invasive progression of gallbladder carcinoma cells.
Adenocarcinoma↗
Cathepsin G enhances human natural killer cytotoxicity.
Cathepsin G is a serine protease located in the azurophil granules of neutrophils. In this study, we investigated the effect of cathepsin G on the functions of human natural killer (NK) cells in vitro. Cathepsin G enhanced NK cytotoxicity rapidly in a dose-dependent fashion. The ability to augment NK cytotoxicity was markedly reduced in the presence of the inhibitor, phenylmethanesulphonyl fluoride (PMSF) or chymostatin, demonstrating that the proteolytic activity of cathepsin G is essential for the induction of NK cytotoxicity. Granulocyte exocytosis is required for NK cell-dependent target killing. Cathepsin G induced the release of the granule enzyme, N-acetyl-beta-D-glucosaminidase, from human NK cells. Moreover, an increase in the cytosolic-free Ca2+ concentration was observed in NK cells after stimulation with cathepsin G. When human granulocytes were stimulated with cytochalasin B and N-formyl-methionyl-leucyl-phenylalanine (fMLP), cathepsin G was released. The cathepsin G released from granulocytes also caused enhancement of NK cytotoxicity. In the presence of serine protease inhibitor the supernatant including cathepsin G obtained from stimulated granulocytes did not enhance NK cytotoxicity, but the stimulated granulocytes did. Highly purified human NK cells treated with cathepsin G enhanced NK cytotoxicity, but NK-depleted lymphocytes did not, demonstrating that cathepsin G regulates NK cytotoxicity independently of other factors. We have shown recently that human cathepsin G binds to human NK cells. These combined data indicate that cathepsin G released from granulocytes binds to NK cells and augments NK cytotoxicity through its protease activity.
Calcium↗
Successful treatment of a persistent cutaneous fistula to the seminal tract: imaging with three-dimensional computed tomography.
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Cutaneous Fistula↗
Expression of target genes by coinfection with replication-deficient viral vectors.
An in vivo transcription system was developed by coinfection of cells with replication-deficient viral vectors. Recombinant baculovirus (AcT7HCVLuc) and fowlpox virus (FPVT7HCVLuc) carrying a cDNA of the hepatitis C virus (HCV) minigene encoding the HCV 5' untranslated region (UTR), a luciferase gene and the 3' UTR, including the 98 nt extra sequence, under the control of the T7 promoter were constructed. The HCV minigene was synthesized in various cells by coinfection with one of these two viruses and recombinant baculovirus (AcCAT7) or adenovirus (AdexCAT7) expressing T7 RNA polymerase under the control of a mammalian promoter. Only a low level of luciferase expression was obtained in cells coinfected with AcT7HCVLuc and either AcCAT7 or AdexCAT7. In contrast, high-level luciferase expression was detected when the same cells were coinfected with FPVT7HCVLuc and either AcCAT7 or AdexCAT7. We further constructed a recombinant fowlpox virus with its HCV minigene extended to contain the whole HCV core protein region. Significantly high levels of expression of HCV core protein were detected in MT-2, COS7 and Vero cells by coinfection with the recombinant fowlpox virus and AdexCAT7. A coinfection system consisting of recombinant fowlpox virus and AdexCAT7 was established for high level of expression of a target gene in various cells.
Adenoviridae↗
Anti-proliferative effects of unmodified antisense oligodeoxynucleotides targeted against c-raf mRNA: use of poly (lysine/serine) copolymers or cationic lipopolyamines.
1. It is now known that nuclease-resistant phosphorothioate antisense oligodeoxynucleotides (ODN) have some actions that are unrelated to antisense mechanisms. In the present study we assessed the anti-proliferative effects of phosphorothioate (PS) and phosphodiester (PO; unmodified) antisense ODN targeted against c-raf mRNA on pancreatic cancer cells in vitro, using poly (lysine/serine) copolymers conjugated with polyethylene glycol (PLSP) or cationic lipopolyamines (Transfectam) as carriers. 2. The anti-proliferative effect of the PO antisense ODN was significantly (P < 0.05) greater than that of the PS ODN, either complexed with PLSP (2 mumol/L ODN) or the Transfectam (0.5 mumol/L ODN). However, the effect of the PS or PO antisense ODN was not dependent on the antisense sequence. The c-raf mRNA levels, assessed by reverse transcription-polymerase chain reaction, were obviously reduced by both PO and PS antisense ODN compared with mismatched ODN when complexed with the Transfectam (1 mumol/L ODN). 3. Although the anti-proliferative effects were mainly unrelated to antisense mechanisms, unmodified antisense ODN complexed with some carriers could be used as anti-tumour agents considering that synthetic carriers can be modified to improve functions, such as delivery.
Cations↗
Value of the free to total prostate specific antigen ratio and prostate specific antigen density for detecting prostate cancer in Japanese patients.
BACKGROUND: This study evaluated the free to total serum prostate specific antigen (f/t PSA) ratio and prostate specific antigen density (PSAD) in detecting prostate cancer in Japanese males with a PSA level between 2.5 and 20.0 ng/mL in a community-based urology practice. METHODS: Twenty-six patients with clinically localized prostate cancer and 44 patients with histologically-proven benign prostatic hyperplasia (BPH) were studied. The serum levels of free PSA (fPSA) and total (t) PSA were determined using a chemiluminescent enzyme immunoassay. The f/t PSA ratio was calculated by dividing the fPSA value by the total PSA value and was compared with the PSA and PSAD via the receiver operating characteristic (ROC) curves. RESULTS: Patients with prostate cancer had a significantly lower f/t PSA ratio than patients with BPH. The PSAD was a superiordiagnostic tool over PSA (P< 0.01) when analyzed by ROC curves. The f/t PSA ratio was also superior to PSA, but lacked significance (P=0.12), and similarly, the PSAD was superior, but not significant, to the f/t PSA ratio. Using a cut-off value of 0.19, the PSAD had a sensitivity of 81% and a specificity of 82%. With a cut-off value of 14.0%, the f/t PSA ratio had a sensitivity of 81% and a specificity of 66%. CONCLUSION: This study showed that PSAD alone improved cancer detection significantly better than PSA. However, it is still unclear whether the f/t PSA ratio is superior to PSA or PSAD in the discrimination between BPH and prostate cancer in Japanese male patients.
Aged↗
Ultrasensitive assay of prostate-specific antigen for early detection of residual cancer after radical prostatectomy.
OBJECTIVES: Perhaps the greatest value of PSA determination in the treatment of prostate cancer is in determining persistent disease after a radical prostatectomy. We investigated the ability of an ultrasensitive PSA assay to detect residual prostate cancer in men at risk for recurrence after a radical prostatectomy. METHODS: Using the Immulite third-generation PSA assay (detection limit, less than 0.003 ng/mL), and the standard IMx PSA assay, we determined PSA levels in 205 serum samples serially obtained from 34 men after a radical prostatectomy. The average days from surgery to serum sampling was 430 (range, 63 to 1296). Patients were classified as having nonaggressive or aggressive cancers, based on clinicopathologic findings. A biochemical relapse was arbitrarily defined. RESULTS: All 17 patients with nonaggressive cancers had PSA values of less than 0.02 ng/mL throughout the sampling period. Two of these patients (12%) had 2 or more consecutive PSA increases and were considered as a biochemical relapse. In contrast, 14 (82%) of 17 patients with aggressive cancers fit criteria of a biochemical relapse. All of the relapses were identified within 2 years after surgery. The IMx assay detected only 7 biochemical relapses during the same sampling period. CONCLUSIONS: Using the Immulite PSA assay, relapse detection times may be shortened allowing for most serological recurrences to be detected within 2 years after a radical prostatectomy. Patients with aggressive cancers may require frequent postoperative PSA determinations with a highly sensitive PSA assay which would allow early intervention when treatments for relapse are effective.
Aged↗
Characteristic pancreatic duct appearance in autoimmune chronic pancreatitis: a case report and review of the Japanese literature.
We report a case demonstrating the progressive narrowing of the pancreatic duct, which is presumed to be characteristic of autoimmune pancreatitis, and we review the 37 cases of chronic pancreatitis in which autoimmunity was suggested as an etiological factor in the Japanese literature. A 55-year-old man presented with abdominal discomfort, jaundice, and diffuse swelling of the pancreas on ultrasonography. Serial endoscopic retrograde pancreatography demonstrated the progression of an irregular narrowing of the main pancreatic duct forming diffusely over the course of 2 months. Because the patient had hyperglobulinemia and tested positive for autoantibodies, he was diagnosed as a case of autoimmune chronic pancreatitis. Steroid therapy was carried out with excellent success.
Autoimmune Diseases↗
A case of glycogen storage disease type Ia with multiple hepatic adenomas and G727T mutation in the glucose-6-phosphatase gene, and a comparison with other mutations previously reported.
We report a case of 23-yr-old man with glycogen storage disease (GSD) type Ia complicated by multiple hepatic adenomas. Analysis of the G-6-Pase gene using peripheral blood sample showed this patient to be homozygous for a G-to-T transversion at nucleotide 727 in exon 5. This mutation is prevalent among Japanese patients, suggesting that specific genotypes may correlate with different clinical courses or outcomes.
Adenoma↗
[A case of hypoxemic acute bronchiolitis presenting with diffuse nodular shadows caused by Mycoplasma pneumoniae].
A fifty year-old female who had previously been well presented with a productive cough and a high fever. Her initial chest X-ray film showed no abnormal lung shadows. Despite partial improvement of the fever and the serum level of acute phase reactant (CRP) in response to intravenous administration of piperacillin, she complained of increasing severity of cough and dyspnea. Follow-up chest X-ray films taken five days after therapy with piperacillin showed diffuse nodular shadows in the mid-to-lower lung fields bilaterally. Chest CT scan disclosed diffuse miliary nodules at the lung periphery and thickening of bronchovascular markings. Chest auscultation revealed late inspiratory coarse crackles and expiratory wheezing, and the patient's arterial oxygen tension was 61 mmHg. Suspected of suffering from primary atypical pneumonia, she was started on therapy with intravenous minocyclin (200 mg/day), two days after treatment her symptoms began improving significantly. Anti-mycoplasma antibody was found to be x 1280, and cold hemoagglutinin x 1024, establishing the diagnosis of Mycoplasma pneumoniae infection. The patient's condition completely recovered following a one week treatment with minocyclin. We concluded that her respiratory infection was caused by piperacillin-sensitive mico-organism, and also Mycoplasma pneumoniae which brought about hypoxic acute bronchiolitis to the patient.
Acute Disease↗
Leukotriene B4 mediates histamine induction of NF-kappaB and IL-8 in human bronchial epithelial cells.
In 16HBE transformed human bronchial epithelial cells, histamine stimulated interleukin (IL)-8 mRNA and protein secretion, and this histamine stimulation was inhibited by the H1-receptor antagonist diphenhydramine (DPH), by the inhibitor of 5-lipoxygenase-activating protein (FLAP) MK-886, by the 5-lipoxygenase inhibitor Zileuton, and by dexamethasone. Histamine stimulated bronchial epithelial cell production of leukotriene B4 (LTB4), and this production was inhibited by FLAP inhibitors MK-886 and L-655,238 and Zileuton. Histamine stimulated IL-8 luciferase reporter gene activity that was inhibited with DPH, dexamethasone, MK-886 and L-655,238, and Zileuton. The inhibition of IL-8 transcription and protein secretion by FLAP inhibitors and Zileuton was reversed with exogenous LTB4. There was increased IL-8 nuclear factor-kappaB (NF-kappaB) DNA-binding activity after histamine stimulation, and this was inhibited by DPH and MK-886. Cytoplasmic phospholipase A2 mRNA levels were also potently induced by histamine. Thus histamine stimulation of bronchial epithelial cells involves binding at H1 receptors, production of LTB4, activation of NF-kappaB and increased expression of IL-8.
Bronchi↗
CsA-sensitive purine-box transcriptional regulator in bronchial epithelial cells contains NF45, NF90, and Ku.
Human bronchial epithelial (HBE) cells express interleukin (IL)-2 [Y. Aoki, D. Qiu, A. Uyei, and P. N. Kao. Am. J. Physiol. 272 (Lung Cell. Mol. Physiol. 16): L276-L286, 1997]. 16HBE-transformed cells contain constitutive and inducible nuclear DNA-binding activity for the purine-box/nuclear factor (NF) of activated T cell (NFAT) target DNA sequence in the human IL-2 enhancer. Transcriptional activation through the purine-box DNA sequence requires stimulation with phorbol 12-myristate 13-acetate + ionomycin, and this activation is inhibited by cyclosporin A. Immunohistochemical staining of 16HBE cells demonstrates nuclear expression of the purine-box DNA-binding proteins NF45 and NF90 and no expression of NFATp or NFATc. NF90 and NF45 associate with the DNA-dependent protein kinase catalytic subunit and the DNA-targeting subunits Ku80 and Ku70 (N. S. Ting, P. N. Kao, D. W. Chan, L. G. Lintott, and S. P. Lees-Miller. J. Biol. Chem. 273: 2136-2145, 1998). Antibodies to Ku potently inhibit the purine-box DNA-binding complex. The purine-box transcriptional regulator in 16HBE cells likely comprises NF45, NF90, Ku80, Ku70, and the DNA-dependent protein kinase catalytic subunit.
Antigens, Nuclear↗
Paraneoplastic cerebellar degeneration with anti-Purkinje cell antibody associated with primary tubal cancer.
In patients with paraneoplastic cerebellar degeneration (PCD) due to gynecologic malignancies, a high titer of anti-Purkinje cell antibody (anti-Yo) has been found. Most patients, however, have limited oncologic disease at the time of onset of neurologic symptoms. We describe 2 cases of PCD due to tubal cancer with anti-Yo antibody. The onset of PCD occurred 4 and 14 months before the detection of cancer, respectively, and the presence of anti-Yo antibody facilitated early laparotomy in both cases. These patients, whose neurologic symptoms have not progressed, have survived without evidence of disease for 81 and 30 months since surgery, respectively. The presence of the anti-Yo antibody in patients with PCD warrants an aggressive approach to diagnosis and treatment of the underlying gynecologic cancer.
Adenocarcinoma↗
Cytokine regulation of the rat proopiomelanocortin gene expression in AtT-20 cells.
Although cytokines are known to be involved in the regulation of ACTH secretion, their effects, along with the molecular mechanisms, on POMC gene expression are not thoroughly characterized. In this study we examined the effects of representative cytokines on transcription of the POMC gene in corticotrophs in vitro using AtT20PL, a clone of the AtT20 cell line stably transfected with approximately 0.7 kilobase of the rat POMC 5'-promoter-luciferase fusion gene. In each experiment, cells were incubated with the cytokine tested, and the changes in POMC 5'-promoter activity were determined by a luciferase assay. The results showed that interleukin-1beta (IL-1beta) stimulated promoter activity in a biphasic manner [weak short term effects (2-3 h) followed by potent long term effects (>12-16 h)]. Tumor necrosis factor-alpha had similar effects, but much less potency. IL-6 showed a profound stimulatory, but only a long term (>20 h), effect. IL-2 did not influence POMC expression. In contrast, interferon-alpha (IFN alpha) and IFN-gamma showed acute stimulatory effects (approximately 4 h) followed by marked inhibitory effects (>8 h). Although the acute effects of IL-1beta, IL-6, and tumor necrosis factor-alpha alone were minimal, they significantly potentiated the stimulatory effect of CRH on POMC expression. Finally, pretreatment of the cells with a broad spectrum tyrosine kinase inhibitor, genistein, abolished or significantly diminished the effects of all cytokines except IFNs. Our results suggest that 1) each cytokine tested has a distinct effect on POMC gene expression; 2) there are positive cross-talk effects between CRH and cytokines at the corticotroph level; and 3) tyrosine phosphorylation cascades are involved in the intracellular signaling mechanisms of some cytokines.
Adrenocorticotropic Hormone↗
Hypertrophic cardiomyopathy with type I CD36 deficiency.
CD36 is a multifunctional membrane-type receptor glycoprotein that reacts with oxidized low-density lipoprotein and long-chain fatty acid (LCFA). A patient presented with hereditary hypertrophic cardiomyopathy (HCM) and type I CD36 deficiency (neither platelets nor monocytes expressed CD36) but showed no myocardial LCFA accumulation. CD36 was expressed in the capillary endothelial cells of the cardiac muscle of a control subject, while the patient's myocardial capillary endothelial cells were completely CD36-negative. These results suggest that type I CD36 deficiency is closely related to hereditary HCM and lack of myocardial LCFA accumulation.
CD36 Antigens↗
Distribution of ABH blood group epitopes on inner surface of dental hard tissue: serological, immunohistochemical and ultrastructural study on odontoblasts.
This study was designed to investigate localization of ABH antigens on the inner surface of human tooth hard tissues. The tooth samples, extracted therapeutically, were cut and dried at room temperature for a few weeks. Scanning electron microscopic observation disclosed that the inner surface was exclusively covered with the odontoblastic zone and virtually no blood vessels remained in the samples. Blood group activities of the tooth fragments, which were detected with absorption-elution test, were markedly decreased when the odontoblastic zone was scraped off. To visualize the activity, the avidin-biotin-peroxidase complex immunostaining was performed on the odontoblasts of fresh teeth followed by embedding. Decalcification process was omitted to preserve the antigenicity. Group specific colorization was successfully developed on the cell surface of the odontoblasts. Immunoreactivity of the cell membrane of the odontoblast including the odontoblastic process was also confirmed by immunotransmission microscopic observation. On the other hand, localization of epitopes on intrinsic dentine without cell components could not be visualized. The results of these experiments indicate that the odontoblasts are one of potent sources of blood group antigenicity for blood grouping of the human teeth.
ABO Blood-Group System↗
Japanese psychology students as psychiatric diagnosticians: application of criteria of mood and anxiety disorders to written case vignettes using the RDC and DSM-IV.
It is commonly believed in Japan that only psychiatrists are capable of providing reliable psychiatric diagnosis. The present study, therefore, examined using a case vignette design, how well Japanese psychology students agreed with a psychiatrist on the diagnoses of mood disorders (major depressive disorder and bipolar disorder) and anxiety disorders (pain disorder, obsessive-compulsive disorder, phobic disorder, and generalized anxiety disorder). The results suggest that appropriately trained Japanese psychology students can apply reliably the diagnostic criteria for these disorders, except for generalized anxiety disorder. It appeared that the students did not identify symptoms of restlessness and nervous tension, which may explain the relatively low reliability of the diagnosis for generalized anxiety disorder. The cross-cultural variation in the experience of anxiety is suggested as an explanation. The present study argues that it is feasible that Japanese nonmedical mental health professionals become familiar with the psychiatric diagnoses.
Adult↗