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Biomedical subjects

M Ando

Publications and source records attributed to M Ando.

At least 19 recordsLinked to original sources
PubMed2001

Osmotic shock induces G1 arrest through p53 phosphorylation at Ser33 by activated p38MAPK without phosphorylation at Ser15 and Ser20.

Osmotic shock induced transient stabilization of p53, possibly due to increased degradation of Mdm2. Stabilized p53 was activated by p38(MAPK), resulting in G(1) arrest through induction of p21(WAF1). Among the postulated phosphorylation sites involved in p53 stabilization or activation (Ser(15), Ser(20), Ser(33), and Ser(46)), only Ser(33) was phosphorylated. Furthermore, interaction of p53 with the transcriptional coactivator p300 was induced, and Lys(382) of p53 was acetylated. Although inhibition of p38(MAPK) did not prevent nuclear accumulation of p53, phosphorylation of Ser(33) was markedly suppressed by SB203580, a specific inhibitor of p38(MAPK). Under these conditions, acetylation of Lys(382) and induction of p21(WAF1) were also inhibited, and cells with elevated levels of p53 showed normal cell cycle progression. Activated p38(MAPK) phosphorylated endogenous p53 at Ser(33) in living cells. In stable transformants expressing dominant negative MKK6, an upstream protein kinase of p38(MAPK), p53 stabilization was induced normally following osmotic shock, but phosphorylation of Ser(33), acetylation of Lys(382), and induction of p21(WAF1) were almost completely inhibited. These results suggest that phosphorylation at Ser(33) by p38(MAPK) is critical for activation of p53 following osmotic shock. Phosphorylation of neither Ser(15) nor Ser(20) was needed in this activation.

Acetylation↗
PubMed2001

Establishment of an expression cloning system for CD4+ T cell epitopes.

We previously reported an epitope presenting vector, pCI, a derivative of a human invariant chain (Ii) expression vector, in which the class II associated invariant chain peptide (CLIP, Ii p89-101) could be substituted with antigenic peptides. In the current study, we used this vector to develop a new expression cloning system to identify CD4+ T cell epitopes. We inserted double-stranded oligo DNAs of randomized sequences into this vector and prepared an epitope-presenting library which loads randomized 13-mer peptides onto HLA class II molecules coexpressed in COS-7 cells. Utilizing this library, we isolated a cross-reactive epitope recognized by a glutamic acid decarboxylase (GAD) 65-autoreactive T cell clone established from a patient with insulin-dependent diabetes mellitus. Although the newly identified epitope (PVQLSNQWHVVGATF) was far different from the original epitope, GAD65 p116-128 (NILLQYVVKSFDR), it did have the capacity to stimulate the T cell clone comparable to that of the original GAD epitope. Our system may be applicable not only for identifying of cross-reactive epitopes for CD4+ T cells of known specificity, but also for detection of epitopes stimulatory for CD4+ T cells the epitopes of which are unknown.

Amino Acid Sequence↗
PubMed2001

Role of monocyte chemoattractant protein-1 in Propionibacterium acnes-induced pulmonary granulomatosis.

The inflammatory process in granulomatous disorders such as sarcoidosis is mainly the consequence of delayed hypersensitivity induced by causative antigens. Propionibacterial DNA was isolated recently by PCR from human sarcoidosis tissue. Hence, we developed a model using sensitized rabbits for T cell-mediated pulmonary granulomatosis induced by Propionibacterium acnes (P. acnes) and investigated the role of monocyte chemoattractant protein-1 (MCP-1) in the pathogenesis of the granuloma formation in vivo. Intravenous injection of P. acnes into sensitized rabbits induced massive pulmonary granulomas on day 3. Maximum levels of MCP-1 in sera and bronchoalveolar lavage fluid (BALF) were detected on day 1 and preceded recruitment of monocyte/macrophages and T cells. In BALF, monocyte chemotaxis peaked 1 day after P. acnes challenge, and T cell chemotaxis peaked 3 days after P. acnes challenge. Anti-MCP-1 IgG inhibited monocyte chemotaxis by 80.2% and T cell chemotaxis by 35.7%. Phenotypic analysis of migrating T cells revealed that activated and memory T cells (CD26(+)/CD45RO(+)) but not naive cells were preferentially attracted to BALF. Administration of MCP-1 antiserum in vivo inhibited the development of granulomas in both size 59.9% reduction and number 28.6% reduction, the number of infiltrating leukocytes in BALF, and the expression of adhesion molecules on leukocytes in peripheral blood and BALF. Our data indicate that MCP-1 plays important roles in granuloma formation by attracting and activating specific types of cells in this model. Furthermore, results suggest that the rabbit model resembles human angiocentric granulomatosis and would be useful for investigating the immunopathogenesis of human pulmonary granulomatosis.

Animals↗
PubMed2001

Stable operation of a 300-m laser interferometer with sufficient sensitivity to detect gravitational-wave events within our galaxy.

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.

Astronomy↗
PubMed2001

Health effects of fluoride pollution caused by coal burning.

Recently a huge amount of fluoride in coal has been released into indoor environments by the combustion of coal and fluoride pollution seems to be increasing in some rural areas in China. Combustion of coal and coal bricks is the primary source of gaseous and aerosol fluoride and these forms of fluoride can easily enter exposed food products and the human respiratory tract. Major human fluoride exposure was caused by consumption of fluoride contaminated food, such as corn, chilies and potatoes. For each diagnostic syndrome of dental fluorosis, a log-normal distribution was observed on the logarithm of urinary fluoride concentration in students in China. Urinary fluoride content was found to be a primary health indicator of the prevalence of dental fluorosis in the community. In the fluorosis areas, osteosclerosis in skeletal fluorosis patients was observed with a high prevalence. A biochemical marker of bone resorption, urinary deoxypyridinoline content was much higher in residents in China than in residents in Japan. It was suggested that bone resorption was stimulated to a greater extent in residents in China and fluoride may stimulate both bone resorption and bone formation. Renal function especially glomerular filtration rate was very sensitive to fluoride exposure. Inorganic phosphate concentrations in urine were significantly lower in the residents in fluorosis areas in China than in non-fluorosis area in China and Japan. Since airborne fluoride from the combustion of coal pollutes extensively both the living environment and food, it is necessary to reduce fluoride pollution caused by coal burning.

Adult↗
PubMed2001

Suppression of pulmonary antibacterial defenses mechanisms and lung damage in mice exposed to fluoride aerosol.

In endemic fluorosis areas in China associated with coal burning, indoor airborne fluoride pollution is severe. To determine the effects of fluoride aerosols on pulmonary antibacterial defense mechanisms and lung damage, mice were exposed to various concentrations of fluoride aerosol (2, 5, or 10 mg/m3) or filtered air (control) for 14 d, 4 h/d in an inhalation chamber. Bactericidal activity against Staphylococcus aureus in the lung and the number and profile of free pulmonary cells, protein content, and lactate dehydrogenase (LDH) activity in bronchoalveolar lavage (BAL) fluid were assessed. Urinary fluoride concentration, an indicator of fluoride exposure, increased in proportion to fluoride aerosol concentration in the chamber. Wet lung weight was significantly higher on d 14 in mice exposed to 10 mg/m3 than in controls. Pulmonary bactericidal activity against S. aureus was concentration-dependently suppressed at 5 and 10 mg/m3 fluoride. The number of alveolar macrophages (AMs) in the BAL fluid of the mice not bacterially challenged decreased significantly at 10 mg/m3 fluoride. The number of polymorphonuclear leukocytes and lymphocytes increased significantly at 10 mg/m3 fluoride exposure. The concentration of total protein (TP) and albumin in BAL supernatant increased significantly at 5 and 10 mg/m3 fluoride exposure, and LDH activity rose markedly at the higher fluoride concentration. Data indicate that fluoride inhalation produces pulmonary cellular alterations that are associated with a diminished ability to cope with infectious bacteria.

Aerosols↗
PubMed2001

Intestinal microflora are necessary for development of spontaneous adenocarcinoma of the large intestine in T-cell receptor beta chain and p53 double-knockout mice.

This study was conducted to confirm the hypothesis that intestinal microflora are required for the development of adenocarcinoma in the colon of the TCRbeta and p53 double-knockout (TCRbeta-/- p53-/-) mouse. Germ-free TCRbeta-/- p53-/- mice were produced. At 7 weeks of age, the animals were divided into two groups (n = 10/group), and one of these groups was conventionalized. Animals of both groups were subjected to histopathological examination for adenocarcinoma of the colon at 4 months of age. There was no development of adenocarcinoma of the colon among the germ-free mice, whereas in the conventionalized group, adenocarcinomas of the ileocecum and cecum were detected in 70% of animals. These results indicate the usefulness of the TCRbeta-/- p53-/- mouse as a colon cancer animal model that develops spontaneous adenocarcinoma of the colon early in life, and suggest that intestinal microflora play a major role in the development of adenocarcinoma of the colon in this animal model.

Adenocarcinoma↗
PubMed2001

Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury.

STUDY DESIGN: A prospective, randomized, and double-blind study comparing high-dose methylprednisolone sodium succinate (MPSS) with placebo, in the treatment of patients with acute cervical spinal cord injury. OBJECTIVES: To evaluate the complications of high-dose MPSS in patients with acute cervical spinal cord injury when administered within 8 hours of injury. SUMMARY OF BACKGROUND DATA: High-dose therapy with MPSS has been demonstrated to improve the recovery of motor function in patients with acute cervical spinal cord injury. However, little is known about the follow-up complications. METHODS: Forty-six patients, 42 men and 4 women (mean age, 60.6 years; range, 18-84), were included in the study: 23 in the MPSS group and 23 in the placebo group. They were treated without surgery for spinal cord injury in the cervical spine, and were enrolled in the trial if a diagnosis had been made and treatment had begun within 8 hours. Complications of high-dose therapy with MPSS were compared with placebo treatment throughout the study period and up to 2 months after injury. RESULTS: The MPSS group had 13 patients (56.5%) with complications, whereas the placebo group had 8 (34.8%). The difference between the two groups was not statistically significant (P = 0.139). There were eight instances of pulmonary complication with MPSS (34.8%) and one instance (4.34%) with placebo (P = 0.009). There were four instances of gastrointestinal complication (17.4%) with MPSS and none with placebo (P = 0.036). Pulmonary (complications were more prevalent in patients aged more than 60 years (P = 0.029). CONCLUSION: Aged patients with cervical spinal injury may be more likely to have pulmonary side effects (P = 0.029) after high-dose therapy with MPSS and thus deserve special care.

Adult↗
PubMed2001

New insights into the thrombopoietic status of patients on dialysis through the evaluation of megakaryocytopoiesis in bone marrow and of endogenous thrombopoietin levels.

The thrombopoietic status of patients with uremia remains unclear. This issue was addressed with particular reference to marrow megakaryocytopoiesis and endogenous thrombopoietin (TPO) levels. A study was conducted in 114 patients on hemodialysis, 43 patients on continuous ambulatory peritoneal dialysis, and 48 age-matched controls. Reticulated platelets, a marker of marrow megakaryocytopoiesis, were measured by flow cytometry. Serum TPO levels, platelet-associated IgG (PAIgG) levels, and hepatitis C virus (HCV) antibody titers were also measured by enzyme-linked immunosorbent assay. Circulating and reticulated platelet counts were significantly lower in the patients on dialysis than in the controls. Thrombocytopenia (less than 150 x 10(9)/L) was most frequent in the HCV-positive hemodialysis patients, who had a higher incidences and higher PAIgG titers. The following results were obtained in the HCV-negative dialysis patients: (1) platelet counts chronologically decreased with years on hemodialysis; (2) platelet counts were associated with the reticulated platelet counts; (3) serum TPO levels were significantly elevated in the dialysis patients, responding to the decrease of reticulated platelets; (4) hematocrits had a positive correlation with serum TPO levels, and serum TPO levels were significantly higher in the patients on hemodialysis who did not require recombinant human erythropoietin therapy than in the other patients. In conclusion, thrombocytopenia is a frequent finding in patients on dialysis. The failure of megakaryocyte production could be the principal cause of the platelet reduction, and the peripheral destruction and sequestration of platelets may be concomitantly involved. Elevation of serum TPO may in part serve as an aid to erythropoiesis in dialysis patients.

Adult↗
PubMed2001

The first total synthesis of (-)-solanapyrone E based on domino Michael strategy.

[figure: see text] A phytotoxin, solanapyrone E, has been synthesized from the decalone prepared by the domino Michael reaction of the kinetic enolate of optically pure acetylcyclohexene with methyl crotonate. After several transformations on the decalone ring, condensation of a methyl acetoacetate equivalent installed a pyrone moiety and introduction of a hydroxymethyl unit into the pyrone ring furnished solanapyrone E.

Alternaria↗
PubMed2001

Efficacy of docetaxel 60 mg/m2 in patients with metastatic breast cancer according to the status of anthracycline resistance.

PURPOSE: To evaluate the efficacy of docetaxel 60 mg/m2 in metastatic breast cancer (MBC) according to the status of anthracycline resistance. PATIENTS AND METHODS: Ninety-nine patients with anthracycline-resistant MBC were treated with docetaxel 60 mg/m2 intravenously for a 90-minute period every 3 to 4 weeks. Anthracycline resistance was defined as primary and secondary resistance. Primary resistance was defined as progression during or within 6 months after completion of adjuvant anthracycline, and no MBC response to a first-line regimen that contained anthracycline. Secondary resistance was defined as progression after a documented clinical response to a first-line anthracycline treatment for MBC. Secondary resistance was further divided into three categories: (1) absolute resistance, or progression during treatment with anthracycline after a period of response; (2) relative resistance, or progression within 6 months after anthracycline administration ended; and (3) sensitive regrowth, or progression more than 6 months after the conclusion of anthracycline administration. RESULTS: The response rate in the 99 patients was 35.4% (95% confidence interval, 30.1% to 44.8%). The response rates according to the status of anthracycline resistance were as follows: primary resistance (n = 46), 19.6%; secondary resistance (n = 53), 49.1% (absolute resistance [n = 16], 56.3%); relative resistance (n = 17), 47.1%; and sensitive regrowth (n = 20), 45.0%. The median time to treatment failure in patients with primary resistance was 2.9 months, compared with 5.2 months in patients with secondary resistance (P = .0022). CONCLUSION: Docetaxel at a dose of 60 mg/m2 seemed to be effective in MBC with secondary resistance to anthracycline. The status of anthracycline resistance is important for the prediction of response to second-line treatment with docetaxel.

Adult↗
PubMed2001

Eight novel mutations of the FBN1 gene found in Japanese patients with Marfan syndrome.

Marfan syndrome (MFS), an autosomal dominant connective tissue disorder, is caused by mutations in the gene encoding fibrillin 1 (FBN1). The clinical spectrum and severity of MFS disorder varies greatly both between and within families. Since there have been only a few reports on the relationship between FBN1 genotypes and clinical phenotypes in Japanese patients, the FBN1 gene was analyzed in 27 Japanese patients diagnosed with MFS. The nucleotide sequence of the 65 exons of the FBN1 gene was analyzed by PCR and direct sequencing. We have identified six polymorphisms and nine mutations including: four missense mutations (C1652Y, Q2054P, D2127Y, C2221R) in six patients, three nonsense mutations (R215X, S813X, R2220X) in three patients, and two frameshift mutations (2567insT, 7790insT) in three patients. Six of these nine mutations were in the calcium-binding epidermal growth factor-like domains all causative mutations detected except for C2221R were novel. It has been reported that the severe phenotypes of infantile MFS correlate with mutations in the mid region of FBN1, however, mutations were not detected in this region in the population analyzed in this study. Our results suggest that the location of the mutation is not the sole determinant of phenotypic severity; rather there is some difference in the genetic basis of MFS between Japanese and Caucasian populations.

Adolescent↗
PubMed2001

High-performance liquid chromatographic assay for glucuronidation activity of 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), in human liver microsomes.

A simple and sensitive assay for glucuronidation activity of 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan (CPT-11), in human liver microsomes by high-performance liquid chromatography (HPLC) with fluorescence detection is reported. The method was validated for the determination of SN-38 glucuronide (SN-38G) with respect to specificity, linearity, recovery, stability, precision, accuracy, and limits of detection and quantitation. There was no interference from matrix and non-enzymatic reactions. The calibration curve for SN-38G was linear from 5 to 500 nM. Average recoveries ranged from 98 to 100% in spiked human liver microsome samples, and the SN-38G was stable at 4 degrees C for at least 72 h. The newly developed method was found to be more sensitive and selective than previous methods using thin layer chromatography and HPLC. The limit of quantitation for SN-38G was 5 nM (2.5 pmol/assay). The intra- and inter-day precision and accuracy were less than 7 and 4%, respectively. The intra- and inter-day precision of enzyme assay for UDP-glucuronosyltransferase (UGT) activity toward SN-38 in human liver microsomes was less than 4%. With this improved sensitivity, the kinetics of SN-38 glucuronidation in human liver microsomes could be determined more precisely. Therefore, this method is applicable to in vitro study on the side effects and drug interactions of CPT-11 using small amounts of biological sample.

Camptothecin↗
PubMed2001

Ruptured left ventricular pseudoaneurysm penetrating into the left pleural cavity.

We experienced a rare case of ruptured left ventricular pseudoaneurysm penetrating into the left pleural cavity. A 77-year-old woman was first diagnosed with unstable angina due to sudden chest pain onset and abnormal electrocardiographic findings. In 2 days, massive left pleural effusion was recognized by chest X-ray, though subsequent computed tomographic scans did not show any aortic pathology. We observed her with left thoracentesis alone. Two days later, cardiac arrest suddenly occurred and emergency surgery was undertaken after resuscitation by percutaneous cardiopulmonary support. In surgery, a moderate amount of intrapericardial hematoma caused by rupture of a left ventricular pseudoaneurysm penetrating into the left pleural cavity was found and successfully repaired. This rare rupture of a left ventricular pseudoaneurysm penetrating into the left pleural cavity generated massive hemo-hydrothorax.

Aged↗
PubMed2001

CD34+-selected autologous peripheral blood stem cell transplantation conditioned with total body irradiation for malignant lymphoma: increased risk of infectious complications.

Although high-dose chemotherapy with autologous peripheral blood stem cell transplantation (autoPBSCT) has been shown or confirmed to be an effective treatment for high-risk and relapsed non-Hodgkin's lymphoma (NHL), relapse after autoPBSCT remains a serious problem. In a clinical trial to overcome relapse, we adopted a treatment plan in which PBSCs purified in vitro to CD34+ cells to deplete tumor cells (CD34+ autoPBSCT), total body irradiation (TBI) of 1200 cGy, and melphalan, 180 mg/m2, were used as a preconditioning regimen. Eighteen patients with relapsed or high-risk NHL participated in the study. This study compared the incidence of complications following CD34+ autoPBSCT preconditioned with the TBI regimen (n = 10): the TBI group; CD34+ autoPBSCT with the non-TBI regimen (n = 8): the non-TBI group; and unselected autoPBSCT with the non-TBI regimen (n = 19): the unselected autoPBSCT control group. After day 30 posttransplantation, 6 of 10 patients treated with the TBI regimen developed 11 infectious complications in total, compared with only 1 of 8 patients treated with the non-TBI regimen and 4 of 19 patients given unselected autoPBSCT. Two fatal complications occurred in the TBI group, but none occurred in the other 2 groups. The CD4+ lymphocyte count at 1 month posttransplantation was significantly lower in the TBI group than in the unselected autoPBSCT group. These findings suggest that the addition of TBI to the preconditioning regimen for CD34+ autoPBSCT is associated with an increased incidence of severe infectious complications after transplantation.

Adult↗
PubMed2001

Bipartite median nerve with a double compartment within the transverse carpal canal.

An anomaly of the median nerve in which there is a division into two branches at the level of the distal third of the forearm is reported. This case was unique in that the ulnar branch of the median nerve passed through a separate compartment within the transverse carpal ligament. It was necessary to decompress both branches of the nerve when releasing the carpal canal.

Carpal Tunnel Syndrome↗