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Biomedical subjects

Y Minami

Publications and source records attributed to Y Minami.

At least 37 records · Page 2Linked to original sources
PubMed2001

Expression of nucleolar protein p120 predicts poor prognosis in patients with stage I lung adenocarcinoma.

BACKGROUND: P120 is a proliferation-associated nucleolar protein found in most human malignant tumors, but not in resting normal cells. In our previous studies, the expression of p120 was statistically correlated with the proliferation capacity in human lung cancer cells and could be a prognostic marker for resected lung adenocarcinoma. PATIENTS AND METHODS: The expression levels of p120 in tumors were assessed by immunohistochemistry in 59 patients with stage I lung adenocarcinoma who underwent radical resection. Using clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using Cox's proportional hazard model. RESULTS: A mean +/- SD of the labeling index of p120 was 35.3+/-14.4%. No significant correlation was found between the expression levels of p120 and clinicopathological factors. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those having low expression of p120 (P = 0.04). Multivariate analysis revealed that p120 served as an independent and strongest prognostic factor for resected lung adenocarcinoma (P = 0.033). CONCLUSION: This article provides the first evidence that the expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected stage I lung adenocarcinoma.

Adenocarcinoma↗
PubMed2001

Down-regulation of alpha6 integrin, an anti-oncogene product, by functional cooperation of H-Ras and c-Myc.

BACKGROUND: The molecular basis of cooperation of H-Ras and c-Myc in regulating cellular behaviour, such as cell adhesiveness, is still poorly understood. To investigate the role of H-Ras and c-Myc in cell adhesiveness, a constitutively active H-RasV12 (H-RasV12) and c-Myc were stably expressed, singly or in combination in a haematopoietic cell line, and the expression and activity of cell adhesion molecules were monitored. RESULTS: We have shown that the ectopic expression of H-RasV12, but not c-Myc alone, in a haematopoietic cell line, induces the activation of very late antigen-6 (VLA-6, alpha6beta1) integrin. Co-expression of H-RasV12 and c-Myc in the same cells further resulted in the induction of expression of vascular cell adhesion molecule-1 (VCAM-1) and the inhibition of expression of alpha6 integrin, a candidate anti-oncogene product, leading to a loss of adhesiveness to laminin (Lm), a ligand for VLA-6. CONCLUSIONS: Cooperation of H-Ras and c-Myc reciprocally regulates expression of the adhesion molecules, alpha6 integrin and VCAM-1. Our results represent an unprecedented account of the cooperation of the oncogene products, H-Ras and c-Myc, to inhibit expression of an anti-oncogene product, alpha6 integrin.

Animals↗
PubMed2001

Both the N- and C-terminal chaperone sites of Hsp90 participate in protein refolding.

Hsp90 is able to bind partially unfolded firefly luciferase and maintain it in a refoldable state; the subsequent successive action of the 20S proteasome activator PA28, Hsc70 and Hsp40 enables its refolding. Hsp90 possesses two chaperone sites in the N- and C-terminal domains that prevent the aggregation of denatured proteins. Here we show that both chaperone sites of Hsp90 are effective not only in capturing thermally denatured luciferase, but also in holding it in a state prerequisite for the successful refolding process mediated by PA28, Hsc70 and Hsp40. In contrast, the heat-induced activity of Hsp90 to bind chemically denature dihydrofolate reductase efficiently and prevent its rapid spontaneous refolding was detected in the N-terminal site of Hsp90 only, while the C-terminal site was without effect. Thus it is most likely that both the N- and C-terminal chaperone sites may contribute to Hsp90 function as holder chaperones, however, in a significantly distinct manner.

Animals↗
PubMed2001

Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1.

A newly identified CX3C-chemokine, fractalkine, expressed on activated endothelial cells plays an important role in leucocyte adhesion and migration. Co-immobilized fractalkine with fibronectin or intercellular adhesion molecule-1 enhanced adhesion of THP-1 cells, which express the fractalkine receptor (CX3CR1), compared with that observed for each alone. That adherence was fractalkine-dependent and was confirmed in blocking studies. However, soluble fractalkine induced little chemotaxis in THP-1 cells in comparison to monocyte chemotactic protein-1 (MCP-1), which induced a strong chemotactic response. Moreover, the membrane form of fractalkine expressed on ECV304 cells reduced MCP-1 mediated chemotaxis of THP-1 cells. These results indicate that fractalkine may function as an adhesion molecule between monocytes and endothelial cells rather than as a chemotactic factor.

Animals↗
PubMed2001

Calcium and pituitary adenylate cyclase-activating polypeptide induced expression of circadian clock gene mPer1 in the mouse cerebellar granule cell culture.

Mammalian circadian clock genes Per1 and Per2 are rhythmically expressed not only in the suprachiasmatic nucleus where the mammalian circadian clock exists, but also in other brain regions and peripheral tissues. The induced circadian oscillation of Per genes after treatment with high concentrations of serum or various drugs in cultured cells suggests the ubiquitous existence of the oscillatory mechanism. These treatments also result in a rapid surge of expression of Per1. It has been shown that multiple signaling pathways are involved in Per1 gene induction in culture cells. We used a dispersed primary cell culture made up of mouse cerebellar granule cells to examine the stimuli inducing the mPer genes and their signaling pathways in neuronal tissues expressing mPer genes. We demonstrated that mPer1, but not mPer2, mRNA expression was dependent on the depolarization state controlled by extracellular KCl concentration in the granule cell culture. Nifedipine treatment reduced mPer1 induction, suggesting that mPer1 mRNA expression depends on intracellular calcium concentration regulated through a voltage-dependent Ca2+ channel. Transient mPer1 mRNA induction was observed after elevating KCl concentration in the medium from 5 mM to 25 mM. This increased expression was suppressed by a calmodulin antagonist, or CaMKII/IV inhibitor, but not by MEK inhibitors. Addition of pituitary adenylate cyclase-activating polypeptide-38 to the medium also induced transient Per1 gene expression. This induction was mimicked by dibutyryl-cAMP and suppressed by a protein kinase A (PKA) inhibitor, but not by MEK inhibitors. These results suggest that Ca2+/calmodulin-dependent protein kinase II/IV- and PKA-dependent pathways are involved in high-KCl and PACAP-induced mPer1 induction, respectively, and neural tissues use multiple signaling pathways for mPer1 induction similar to culture cells.

Animals↗
PubMed2001

Loss of mRor1 enhances the heart and skeletal abnormalities in mRor2-deficient mice: redundant and pleiotropic functions of mRor1 and mRor2 receptor tyrosine kinases.

The mammalian Ror family of receptor tyrosine kinases consists of two structurally related proteins, Ror1 and Ror2. We have shown that mRor2-deficient mice exhibit widespread skeletal abnormalities, ventricular septal defects in the heart, and respiratory dysfunction, leading to neonatal lethality (S. Takeuchi, K. Takeda, I. Oishi, M. Nomi, M. Ikeya, K. Itoh, S. Tamura, T. Ueda, T. Hatta, H. Otani, T. Terashima, S. Takada, H. Yamamura, S. Akira, and Y. Minami, Genes Cells 5:71-78, 2000). Here we show that mRor1-deficient mice have no apparent skeletal or cardiac abnormalities, yet they also die soon after birth due to respiratory dysfunction. Interestingly, mRor1/mRor2 double mutant mice show markedly enhanced skeletal abnormalities compared with mRor2 mutant mice. Furthermore, double mutant mice also exhibit defects not observed in mRor2 mutant mice, including a sternal defect, dysplasia of the symphysis of the pubic bone, and complete transposition of the great arteries. These results indicate that mRor1 and mRor2 interact genetically in skeletal and cardiac development.

Animals↗
PubMed2001

Critical role of Caenorhabditis elegans homologs of Cds1 (Chk2)-related kinases in meiotic recombination.

Although chromosomal segregation at meiosis I is the critical process for genetic reassortment and inheritance, little is known about molecules involved in this process in metazoa. Here we show by utilizing double-stranded RNA (dsRNA)-mediated genetic interference that novel protein kinases (Ce-CDS-1 and Ce-CDS-2) related to Cds1 (Chk2) play an essential role in meiotic recombination in Caenorhabditis elegans. Injection of dsRNA into adult animals resulted in the inhibition of meiotic crossing over and induced the loss of chiasmata at diakinesis in oocytes of F(1) animals. However, electron microscopic analysis revealed that synaptonemal complex formation in pachytene nuclei of the same progeny of injected animals appeared to be normal. Thus, Ce-CDS-1 and Ce-CDS-2 are the first example of Cds1-related kinases that are required for meiotic recombination in multicellular organisms.

Amino Acid Sequence↗
PubMed2001

Evaluation of posttreatment response of hepatocellular carcinoma with contrast-enhanced coded phase-inversion harmonic US: comparison with dynamic CT.

PURPOSE: To assess the reliability of contrast material-enhanced real-time gray-scale ultrasonography (US) in evaluating posttreatment response of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty HCC nodules were examined with contrast-enhanced coded phase-inversion harmonic US before and after treatment. Intratumoral vascularity was assessed with continuous imaging in the early arterial phase and with interval-delay scanning to depict tumor parenchymal flow during the blood pool phase. Vascular findings at US were compared with those at dynamic computed tomography (CT). RESULTS: In 50 HCC nodules before treatment, positive enhancement of tumor vessels and tumor parenchymal flow (stain) were observed in 47 (94%) and 46 (92%), respectively. Either tumor vessel or stain was visualized with coded harmonic US in 49 of 50 nodules. Eighty-one coded harmonic US studies were performed in 49 posttreatment HCC nodules. Compared with dynamic CT, the sensitivity, specificity, and accuracy of coded harmonic US in helping to detect positive enhancement in pretreatment HCC were 98% (49 of 50), 100% (50 of 50), and 98% (49 of 50), respectively. After treatment, positive enhancement of tumor vascularity was observed in 39 (48%) of 81 posttreatment studies, and no enhancement was observed in others (52%). Coded harmonic US demonstrated partial and no enhancement of tumor vascularity in four and one nodule, respectively; after transcatheter arterial embolization with iodized oil, evaluation of tumor vascularity with dynamic CT was difficult because of the presence of oil. CONCLUSION: With enhancement, coded harmonic US depicted tumor vascularity by showing tumor vessels in a real-time fashion at continuous imaging and tumor parenchymal flow at interval-delay scanning.

Adult↗
PubMed2001

Hepatocellular carcinoma: depiction of tumor parenchymal flow with intermittent harmonic power Doppler US during the early arterial phase in dual-display mode.

PURPOSE: To assess the effectiveness of contrast material-enhanced intermittent harmonic Doppler ultrasonography (US) in depicting tumor vessels and tumor parenchymal flow (stain) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty-eight patients with 65 HCC nodules were examined by using intermittent harmonic power Doppler US and digital subtraction harmonic B-mode US, both with intravenous administration of SH U 508A. Vascular findings at early arterial phase harmonic US were classified as positive enhancement or nonenhancement, depending on the tumor vascularity relative to the surrounding liver parenchyma. These results were compared with those of three-phase helical dynamic computed tomography (CT). RESULTS: For hypervascular HCCs, there was excellent depiction of tumor vessels and tumor stain with the two intermittent harmonic US methods. The sensitivity and specificity for depiction of tumor vascularity were 93% (41 of 44 nodules) and 100% (21 of 21), respectively, with intermittent harmonic power Doppler US and 86% (38 of 44) and 100% (21 of 21), respectively, with subtraction US, as compared with these values at dynamic CT. Attenuation was an important factor in the depictability of tumor vascularity at harmonic US. CONCLUSION: Contrast-enhanced intermittent harmonic US enables noninvasive demonstration of tumor vessels and especially tumor stain in HCC.

Adult↗
PubMed2001

Contrast-enhanced subtraction harmonic sonography for evaluating treatment response in patients with hepatocellular carcinoma.

OBJECTIVE: Our objective was to assess the usefulness of contrast-enhanced subtraction harmonic sonography in evaluating the treatment response of patients with hepatocellular carcinoma. SUBJECTS AND METHODS: Thirty-two hepatocellular carcinoma lesions in 26 patients (age range, 44-85 years; mean age, 66 years) were examined with Levovist-enhanced intermittent harmonic imaging before and after therapy. A Toshiba Powervision 8000 was used. A subtraction image was obtained by digitally subtracting the last-frame harmonic image from the first-frame image when multishot mode was preset. Results of contrast-enhanced CT were compared with the results of subtraction harmonic imaging. RESULTS: Before therapy, an enhancement pattern of tumor vascularity was seen for 93.8% (30/32) of hepatocellular carcinoma nodules on subtraction harmonic imaging. After therapy, subtraction harmonic imaging showed 46.7% (14/30) enhancement (incomplete tumor necrosis) and 53.3% (16/30) no enhancement (complete tumor necrosis). When dynamic CT was the gold standard, the sensitivity, specificity, and accuracy of subtraction harmonic imaging were 93.3%, 100%, and 96.7%, respectively. Intratumoral flow signals in hepatocellular carcinoma after therapy on harmonic imaging were used as a guide to target additional percutaneous therapy. CONCLUSION: Digital subtraction contrast-enhanced harmonic imaging can depict tumor vascularity in hepatocellular carcinoma after therapy sensitively and accurately. Because it is easy to perform and provides real-time needle insertion guidance, it may be preferable to perform after localized therapy to monitor treatment response, which will reduce unnecessary CT scanning.

Aged↗
PubMed2001

Decreases in phenytoin hydroxylation activities catalyzed by liver microsomal cytochrome P450 enzymes in phenytoin-treated rats.

Phenytoin, 5,5-diphenylhydantoin, is a widely used anticonvulsant agent with a variety of toxicities, including drug interactions. The formation of four oxidative metabolites, 4'-hydroxylated (4'-HPPH), 3'-hydroxylated (3'-HPPH), a catechol (3',4'-diHPPH), and the 3',4'-dihydrodiol form of phenytoin was examined in rat liver microsomes. In 11 cDNA-expressed rat P450 enzymes tested, CYP2C6 had the highest activities in 4'- and 3'-HPPH formation from phenytoin, followed only by CYP2C11. In contrast, CYP2C11 had high activity for 3',4'-diHPPH formation from 4'-HPPH, followed by CYP2C6. The rates of 4'-HPPH and 3',4'-diHPPH formation from phenytoin in liver microsomes in the presence of NADPH were significantly decreased by oral administration of phenytoin (300 mg/kg for 20 days) to rats, despite the increase in P450 contents. However, the cumene hydroperoxide-supported formation of 3',4'-dihydrodiol and 4'-HPPH from phenytoin was induced by phenytoin administration. Hydrogen peroxide formation in reaction mixtures with NADPH was induced by the administration of phenytoin; however, the coupling ratio of phenytoin oxidation was decreased in phenytoin-induced liver microsomal P450 systems. These results suggested that phenytoin could not stimulate its own apparent oxidative metabolism by liver P450s induced with phenytoin administration. The increase of unmetabolized phenytoin and byproducts of oxygen generated in the phenytoin-induced liver microsomal P450 system may be involved in phenytoin-related drug toxicity.

Animals↗
PubMed2001

[A case of malignant pheochromocytoma associated with von Recklinghausen's disease].

A 48-year-old woman suffering from chest and lumbar pain was referred to our clinic for treatment. She had a history of von Recklinghausen's disease with multiple café-au-lait spots and neurofibromatosis. Computed tomography demonstrated a large tumor in the left adrenal gland and a small lesion in the liver, with the levels of plasma and urinary catecholamines being elevated. 131I-metaiodobenzylguanidine (MIBG) scintigraphy showed abnormal accumulations in the left adrenal tumor and multiple-bone lesions. A diagnosis of malignant pheochromocytoma with liver and bone metastases was made, and the patient received chemotherapy. Seven months after the diagnosis of malignant pheochromocytoma, she died of pulmonary edema due to disease progression. Autopsy revealed malignant pheochromocytoma with liver, lung, bone and lymph nodes metastases. We reviewed the literature on pheochromocytoma associated with von Recklinghausen's disease. To our knowledge, only 7 cases of malignant pheochromocytoma associated with von Recklinghausen's disease have been reported in Japan.

Adrenal Gland Neoplasms↗
PubMed2001

[On total care we have learned during home care hospice study trips in USA--from the experiences of 8 year times visits to America with medical students for practice].

Every year since 1993, as a part of the medical education program of Osaka University, I have taken 10 or more medical students and others to hospices in the USA to study hospice and home care during two weeks. We visit patients and interview them. Palliative care treatment is by definition care treatment designed to relieve pain and distress, pain and symptom management is essentially important. It was very impressive for us to see that in American hospices total care was provided by many kinds of professionals working as a team. Socio-psychological and spiritual care played important roles in total care, which was provided not only to the patients but also to the families, care-takers, and bereaved families after death. We saw home was the best and most natural place for them. I think we have much to learn from these experiences, such as that doctors and nurses are not bosses, but equals among professionals. Also, that home care is not a temporary place in an institution, and that there are many terminal illnesses, besides cancer and AIDS, for which patients require home care.

Comprehensive Health Care↗
PubMed2000

Hybrid proteasomes. Induction by interferon-gamma and contribution to ATP-dependent proteolysis.

Eukaryotic cells contain various types of proteasomes. Core 20 S proteasomes (abbreviated 20 S below) have two binding sites for the regulatory particles, PA700 and PA28. PA700-20 S-PA700 complexes are known as 26 S proteasomes and are ATP-dependent machines that degrade cell proteins. PA28 is found both in previously described complexes of the type PA28-20 S-PA28 and in complexes that also contain PA700, as PA700-20 S-PA28. We refer to the latter as "hybrid proteasomes." The relative amounts of the various types of proteasomes in HeLa extracts were determined by a combination of immunoprecipitation and immunoblotting. Hybrid proteasomes accounted for about a fourth of all proteasomes in the extracts. Association of PA28 and proteasomes proved to be ATP-dependent. Hybrid proteasomes catalyzed ATP-dependent degradation of ornithine decarboxylase (ODC) without ubiquitinylation, as do 26 S proteasomes. In contrast, the homo-PA28 complex (PA28-20 S-PA28) was incapable of degrading ODC. Intriguingly, a major immunomodulatory cytokine, interferon-gamma, appreciably enhanced the ODC degradation in HeLa and SW620 cells through induction of the hybrid proteasome, which may also be responsible for the immunological processing of intracellular antigens. Taken together, we report here for the first time the existence of two types of ATP-dependent proteases, the 26 S proteasome and the hybrid proteasome, which appear to share the ATP-dependent proteolytic pathway in mammalian cells.

Adenosine Triphosphate↗
PubMed2000

A critical role for the proteasome activator PA28 in the Hsp90-dependent protein refolding.

The 90-kDa heat shock protein, Hsp90, was previously shown to capture firefly luciferase during thermal inactivation and prevent it from undergoing an irreversible off-pathway aggregation, thereby maintaining it in a folding-competent state. While Hsp90 by itself was not sufficient to refold the denatured luciferase, addition of rabbit reticulocyte lysate remarkably restored the luciferase activity. Here we demonstrate that Hsc70, Hsp40, and the 20 S proteasome activator PA28 are the effective components in reticulocyte lysate. Purified Hsc70, Hsp40, and PA28 were necessary and sufficient to fully reconstitute Hsp90-initiated refolding. Kinetics of substrate binding support the idea that PA28 acts as the molecular link between the Hsp90-dependent capture of unfolded proteins and the Hsc70- and ATP-dependent refolding process.

Amino Acid Sequence↗
PubMed2000

Activation of calpain precedes morphological alterations during hydrogen peroxide-induced apoptosis in neuronally differentiated mouse embryonal carcinoma P19 cell line.

In order to reveal neurodegeneration elicited by reactive oxygen intermediates (ROI), neuronally differentiated cells from mouse embryonal carcinoma P19 cell line were exposed to hydrogen peroxide (H2O2). Enhanced protein-phosphorylation on tyrosine residues was detectable within 5 min of exposure to H2O2, and gradual rises in intracellular free Ca2+ level and in calpain activity were observed. Furthermore, H2O2 stimulation of differentiated P19 cells for 24 h resulted in morphological alterations in somas as well as neurites. Also, within 6 h of H2O2 treatment DNA fragmentation has been detected. Taken together, these results suggest that oxidative stress induces degradation of cytoskeletal proteins presumably resulting from increased intracellular Ca2+ concentration and subsequent activation of calpain.

Animals↗
PubMed2000

Intercellular adhesion molecule 1 underlies the functional heterogeneity of synovial cells in patients with rheumatoid arthritis: involvement of cell cycle machinery.

OBJECTIVE: To investigate whether synovial cells from rheumatoid arthritis (RA) synovium can be divided into 2 functionally different subpopulations: active or proliferative cells and apoptotic cells. METHODS: Expression of cell surface and cytoplasmic molecules on synovial cells was assessed by immunohistochemistry, flow cytometry, or Western blotting. Cells were categorized as intercellular adhesion molecule 1 (ICAM-1) positive or negative based on positive and negative selection of antibody-coated beads. Cell cycle and apoptosis were assessed using propidium iodide staining, TUNEL method, and DNA fragmentation. RESULTS: Expression of ICAM-1 and Fas was noted mainly in the synovial lining to sublining layer in vivo, and synovial cells could be clearly distinguished as ICAM-1 positive or negative. The expression of Fas was higher on ICAM-1-positive cells than on ICAM-1-negative cells in vitro. The functional and phenotypic heterogeneity between ICAM-1-positive and -negative cells was further emphasized by cell cycle machinery. The majority of ICAM-1-positive cells were arrested at the G0/G1 phase, whereas many of the ICAM-1-negative cells were at the S to G2/M proliferating phase. In ICAM-1-positive cells, p53 and p21 expression was up-regulated and cyclin-dependent protein kinase 6 activity was inhibited. Most ICAM-1-positive cells were apoptotic (as evidenced by TUNEL positivity and DNA fragmentation). ICAM-1-positive cells were induced not only by interleukin-1beta, but also by Fas crosslinking. CONCLUSION: ICAM-1-positive synovial cells represent growth arrest and subsequent apoptosis, whereas ICAM-1-negative cells are proliferative. Such differences in regulation of the cell cycle based on ICAM-1 status are important determinants of the lifespan, proliferation, and growth arrest of RA synoviocytes.

Apoptosis↗