Biomedical subjects

Y Minami

Publications and source records attributed to Y Minami.

At least 37 records · Page 2Linked to original sources

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↗

PubMed2000

Determinants of infant feeding method in relation to risk factors for breast cancer.

BACKGROUND: Breastfeeding is considered to be an important factor for maternal and children's health. However, the epidemiological findings related to the effect of breastfeeding on women's health, especially with respect to breast cancer development, are inconsistent. Determinants of infant feeding method may contribute to the inconsistency. METHODS: A total of 24,769 women aged 40-64 in Miyagi Prefecture, Japan, responded to a self-administered questionnaire survey in 1990. Using the data obtained from 22,085 parous women, we calculated odds ratios (ORs) for the choice of "breastfeeding only" during reproductive period. RESULTS: Late age at menarche (> or = 16 years, OR = 1.57) and high body mass index (BMI) at 20 years of age (> or = 24, OR = 1.31) were associated with the choice of breastfeeding only. Late age at birth of first child (> or = 28 years, OR = 0.29), history of breast cancer in mother (OR = 0.68), and high educational level (more than a high school education, OR = 0.53) reduced the possibility of choosing breastfeeding only. CONCLUSION: The results indicate that the choice of infant feeding method is associated with several breast cancer risk factors. Based on this finding, we should construct appropriate breast cancer risk models for parous women and investigate the changes in the effects of breastfeeding and other breast cancer risk factors among these risk models. Especially in a risk model controlling for breastfeeding, the effects of other breast cancer risk factors should be reevaluated. Through comparisons among different risk models, we may find the best-fitted risk model and identify the true effect of breastfeeding.

Adolescent↗

PubMed2000

Optimal management of the axilla in patients with breast cancer.

BACKGROUND: Although most surgeons perform some form of axillary lymph node dissection (ALND) as part of locoregional management of operable breast cancer, the extent of dissection remains controversial. PATIENTS AND METHODS: Observation of the axilla trial (protocol I) and partial dissection trial (protocol I) began in January 1996. Between January 1996 and May 2000, 45 post-menopausal and 207 women with clinically node-negative breast cancer were enrolled into protocol I and protocol II respectively. RESULTS: The 4-year cumulative incidence rate of axillary recurrence was 7% in patients with untreated the axilla. The 4-year overall survival rate was 98% in patients with untreated the axilla. The 4-year disease-free and overall survival rates were 96% and 98% respectively in patients treated with partial dissection. CONCLUSION: Total axillary dissection seems to be unnecessary in Japanese breast cancer patients with relatively small tumors.

Adult↗

PubMed2000

Mortality and cancer incidence in patients with Parkinson's disease.

To investigate the risks of mortality and cancer incidence in Parkinson's disease (PD) we studied the prognosis of 246 PD patients in a community. The cohort of PD patients was identified in 1984, and survival, mortality, relocation, and cancer incidence during 1984-1992 were examined retrospectively in 1994. The risk was measured by a standard effect estimate, i.e., the standardized mortality ratio (SMR) or the standardized incidence ratio (SIR), compared with the rates in the general population. During the observation period 696 person-years in PD men and 1018 person-years in PD women were accumulated, and 49 PD men and 53 PD women died. The risk of mortality in PD was significantly increased in both sexes (SMR: men 1.74, women 1.97). In addition, the risk of cancer incidence was evaluated in 228 patients aged under 80 years; 8 PD men and 7 PD women developed cancer. The risk of overall cancer incidence in PD was less than 1 in either sex, but not significantly. The risk of breast cancer in PD women was significantly increased (SIR: 5.49), but the 95% confidence interval was wide (1.10-16.03). The results indicate that PD patients in a community have a twofold higher risk of mortality, and that PD may be associated with an increased risk of breast cancer in women.

Adult↗

PubMed2000

Differential interaction of Cbl with Grb2 and CrkL in CD2-mediated NK cell activation.

Natural killer (NK) cells participate in both innate and adoptive immunity by their prompt secretion of cytokines and by their ability to lyse virally infected cells or tumor cells. CD2 is surface glycoprotein receptors and crucial for NK cell activation. However, molecular events involved in CD2-mediated NK cell activation have not been fully elucidated. Cbl-Grb2 and Cbl-CrkL interactions have been implicated in T cell and B cell receptor, and cytokine receptor signaling. Here we analyzed tyrosine phosphorylation and interactions of Cbl with adapter proteins, Grb2 and CrkL, in NK3.3 cells. CD2 crosslinking results in the marked tyrosine phosphorylation of Cbl in an antibody concentration- and time-dependent manner. Immunodepletion studies reveal that Grb2-associated tyrosine phosphorylated p120 kDa protein is Cbl. In vitro binding studies using GST-fusion proteins demonstrate that Cbl constitutively associates with the SH3 domains of Grb2, with a preference for the amino-terminal domain. In addition, we demonstrate that CrkL associates with a large portion of tyrosine phosphorylated Cbl after CD2 stimulation of NK3.3 cells. In contrast to constitutive Cbl association with Grb2, tyrosine phosphorylated Cbl interacts with CrkL via its SH2 domain only after CD2 stimulation. Although the precise roles of interactions of Cbl with Grb2 and CrkL in NK cell activation remains to be elucidated, their tyrosine phosphorylation, in addition to the multiple protein interactions described here, strongly suggest that interactions of Cbl with Grb2 and CrkL may play pivotal roles in CD2-mediated NK cell activation.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Changes in serum hepatic fibrosis markers in biochemical responders to interferon therapy for chronic hepatitis C.

Serum hepatic fibrosis markers (7s domain of type IV collagen, N-terminal peptide of type III procollagen, and hyaluronate) were determined during and after a 6-month interferon treatment of patients with chronic hepatitis C. Changes in these markers were compared among the patients who showed a sustained normalization of serum alanine transaminase (ALT) levels with and without eradication of serum hepatitis C virus RNA (complete responders and biochemical responders) and nonresponders. In the case of complete responders, the serum 7s domain of type IV collagen and the N-terminal peptide of type III procollagen levels decreased at the end and 24 weeks after the end of the treatment. Hyaluronate levels were significantly decreased 24 weeks after the end of the treatment, as compared with those prior to the treatment. During and after interferon treatment, changes in these markers in the case of biochemical responders were nearly the same as those in the complete responders. These results suggest that serum hepatic fibrosis markers decrease in patients with chronic hepatitis C who show a sustained normalization of ALT after interferon treatment, even if serum hepatitis C virus RNA fails to be eradicated.

Journal Article↗

PubMed2000

A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer.

Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium ion channel family, and its site-directed active mutant (MDEG-G430F) induces massive Na+ influx into cells, leading to cell ballooning and cell bursting. We attempted a novel therapeutic approach for gastric cancers by transferring MDEG-G430F into cancer cells using tumor-specific promoters. In carcinoembryonic antigen (CEA)-producing gastric cancer cells, the level of cell death observed when MDEG-G430F was used with a CEA promoter was similar to that observed when using a potent nonspecific promoter such as the cytomegalovirus promoter. In an in vivo study, fusogenic liposome complexes containing MDEG-G430F driven by the CEA promoter were injected intraperitoneally into CEA-producing gastric cancer cells in a mouse peritoneal dissemination model. Although all 15 of the control mice were dead by 50 days postinoculation, 13 of the 15 mice treated with MDEG-G430F survived. These results indicate that transferring MDEG-G430F into cancer tissues using tumor-specific promoters can achieve striking and selective cancer cell death irrespective of the transcriptional efficiency of the promoters used in vivo, and suggest that this approach is a promising new strategy for cancer gene therapy.

Acid Sensing Ion Channels↗

PubMed2000

Involvement of CD95-independent caspase 8 activation in arsenic trioxide-induced apoptosis.

Arsenic trioxide (As2O3)-treatment is effective in acute promyelocytic leukemia (APL) patients with t(15;17). Clinically achievable concentrations of As2O3 induce apoptosis in NB4, an APL cell line, in vitro. Here, to study the mechanism of As2O3-induced apoptosis, we established an As2O3-resistant subline, NB4/As. Growth of NB4/As was inhibited by 50% after 2 day-treatment (IC50) at 1.6 microM As2O3, whereas IC50 of NB4 was 0.3 microM. Degradation of PML-RARalpha and change of the PML-subcellular localization were similarly induced by As2O3 in NB4 and NB4/As, suggesting that their contribution to apoptosis is small. Treatment with 1 microM As2O3 induced the activation of caspase 3 as well as a loss of mitochondrial transmembrane potential (deltapsim) in NB4 but not in NB4/As. Caspase 8 and Bid were also activated by As2O3 in NB4 but not in NB4/As. In NB4, an inhibitor of caspase 8 blocked not only the activation of caspase 3 but also the loss of deltapsim. Neither cell line expressed CD95/Fas, and agonistic anti-Fas antibody (CH-11) failed to cause apoptosis. Neither antagonistic anti-CD95/Fas antibody nor anti-Fas ligand antibodies influenced the As2O3-induced apoptosis. NB4/As had a higher concentration of intracellular glutathione (GSH) than NB4 (96 vs 32 nmol/mg). Reduction of the GSH level by buthionine sulfoxide (BSO) completely restored the sensitivity to As2O3 in NB4/As. Furthermore, caspase activation and the loss of deltapsim were recovered by combination treatment with BSO. These findings suggest that the As2O3 treatment activates caspase 8 in a CD95-independent but GSH concentration-dependent manner. In combination with BSO, As2O3 might be applied to therapy of leukemia/cancers which are insensitive to the clinically achievable concentrations of As2O3.

Antineoplastic Agents↗

PubMed2000

Mouse Ror2 receptor tyrosine kinase is required for the heart development and limb formation.

BACKGROUND: A mouse receptor tyrosine kinase (RTK), mRor2, which belongs to the Ror-family of RTKs consisting of at least two structurally related members, is primarily expressed in the heart and nervous system during mouse development. To elucidate the function of mRor2, we generated mice with a mutated mRor2 locus. RESULTS: Mice with a homozygous mutation in mRor2 died just after birth, exhibiting dwarfism, severe cyanosis, and short limbs and tails. Whole-mount in situ hybridization analysis showed that mRor2 was expressed in the branchial arches, heart and limb/tailbuds, in addition to the developing nervous system. The mutants had cardiac septal defects, mainly a ventricular septal defect. In addition, an examination of the skeletal systems revealed that the mutants had shorter limbs, vertebrae and facial structure, with a particular defect in their distal portions, and that almost no calcification was observed in their distal limbs. Histological examination showed abnormalities in the chondrocytes. CONCLUSIONS: Our findings suggest that mRor2 plays essential roles in the development of the heart and in limb/tail formation, in particular cardiac septal formation and ossification of distal portions of limbs and tails.

Animals↗

PubMed2000

Tissue and intracellular localization of indican and the purification and characterization of indican synthase from indigo plants.

Indican (indoxyl beta-D-glucoside) was found to accumulate only in green leaves of the indigo plant, and not in any other tissues. Comparisons of the indican content of protoplasts and vacuoles showed that indican was stored only in the vacuole of the cell. Indican content appeared and increased with the appearance and growth of leaves. In mature plants, the younger leaves contained larger amounts of indican than the older ones. Cell extracts of young leaves of indigo plant catalyzed the synthesis of indican from UDP-glucose and indoxyl. Indican synthase was extracted and purified from young leaves. The enzyme was separated into two fractions by anion-exchange chromatography. The enzyme in the fraction which was eluted by 0.1 M NaCl had a molecular weight of 53,000 by SDS-PAGE. Optimum pH of the enzyme was at about 10.0, indicating that the enzyme is likely localized in a different intracellular compartment from that of indican storage. The enzyme showed normal Michaelis-Menten kinetics and a K(m) value of 0.13 mM for UDP-glucose.

Glucosyltransferases↗

PubMed2000

[Absorption of a vaginal contraceptive, nonoxynol (polyoxyethylene nonylphenyl ether) and its metabolism to nonylphenol in female rabbits].

After intravaginal administration of a spermicide, nonoxynol (polyoxyethylene nonylphenyl ether, NPE) in female rabbits, the pharmacokinetics of NPE were examined by the HPLC method. The plasma levels after administration of NPE revealed a considerable amount of absorption of NPE into the circulation and the bioavailability after intravaginal administration was calculated to be 66% by comparison with that after intravenous administration. Unchanged NPE was not excreted into the urine in significant amounts even on intravenous administration. Nonylphenol (NP), a presumed metabolite of NPE, was simultaneously analyzed using GC-MS to assess the risk by its endocrine disrupting effects. Although the NP concentrations in the plasma were all below the lower limit of quantitation (10 ng/ml), small amounts of NP and its glucuronide conjugate were detected in the urine after intravaginal administration of NPE. Thus it was suggested that at least part of NPE absorbed in the circulation was metabolized to give NP. However, the sum of NP and its conjugate excreted in the urine was very small amounts (0.22% of dose). Therefore, it was assumed that the production of NP was not in the major pathway of the NPE metabolism.

Administration, Intravaginal↗

PubMed2000

Subacute tuberculous pericarditis with fibroelastic constriction diagnosed upon pericardiectomy.

A patient with subacute pericarditis showed no evidence suggesting tuberculosis until pericardiectomy was performed because of hemodynamic deterioration. The excised pericardium had a rubbery fibroelastic consistency; histologically, there were granulomatous changes characteristic of tuberculosis. Although tuberculous pericarditis is a difficult diagnosis, this case illustrates the diagnostic and therapeutic importance of early pericardiectomy before myocardial inflammatory infiltration occurs together with end-stage pericardial fibrosis and calcification.

Diagnostic Techniques, Cardiovascular↗

PubMed2000

Intercellular adhesion molecule 1 discriminates functionally different populations of human osteoblasts: characteristic involvement of cell cycle regulators.

The concept of differential regulation of certain adhesion molecules on different cell subsets and their relevance to cell functions has emerged in recent years. The initial event in bone remodeling is an increase in osteoclastic bone resorption and cell adhesion between osteoclastic precursors and bone marrow stromal cells or osteoblasts is known to commit the osteoclast development. Here, we show that human osteoblasts can be divided into two subsets based on the expression of the intercellular adhesion molecule (ICAM)-1; ICAM-1+ osteoblasts highly adhered to monocytes, including osteoclast precursors, produced osteoclast differentiation factor (ODF), and induced multinuclear osteoclast-like cell formation. Anti-ODF monoclonal antibody (mAb) did not inhibit the adhesion of monocytes to osteoblastic cells, whereas anti-leukocyte function-associated antigen (LFA)-1, a receptor for ICAM-1, mAb blocked the adhesion. We thereby propose that the higher affinity adhesion via LFA-1/ICAM-1 is prerequisite for efficient function of membrane-bound ODF during osteoclast maturation. The functional characteristics of ICAM-1+ osteoblasts were emphasized further by cell cycle regulation, as manifested by (i) up-regulation of p53 and p21, (ii) reduction of activity of cyclin-dependent kinase (cdk) 6, (iii) underphosphorylation of retinoblastoma protein, (iv) increased Fas but reduced bcl-2 expression, and (v) majority of cells remained at G0/G1 phase. Furthermore, ICAM-1+ osteoblasts were induced by interleukin-1beta (IL-1beta). Taken together, we propose that the differentiation of osteoblasts to ICAM-1+ subpopulation by inflammatory cytokines plays an important role in osteoporosis, which is observed in patients with chronic inflammation, because ICAM-1+ osteoblasts can bias bone turnover to bone resorption, committing osteoclast maturation through cell adhesion with its precursor, and the majority of ICAM-1+ osteoblasts arrested at G0/G1 phase. Such regulation of cell cycle arrest also is an important determinant of the life span of cells in bone in which continuous bone remodeling maintains its homeostasis.

Carrier Proteins↗