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Biomedical subjects

M Miyake

Publications and source records attributed to M Miyake.

At least 127 records · Page 7Linked to original sources
PubMed1998

KAI1/CD82 expression in nonsmall cell lung carcinoma is a novel, favorable prognostic factor: an immunohistochemical analysis.

BACKGROUND: The KAI1/CD82 gene, the product of which is a member of the transmembrane-4 superfamily, is a suppressor of metastasis; as a result, it is inversely associated with tumor progression and is a favorable prognostic factor in some tumors. This study was performed to determine the prognostic value of KAI1/CD82 protein levels in nonsmall cell lung carcinoma (NSCLC). In addition, levels of KAIl/CD82 expression in metastatic lesions were determined and compared with those in primary NSCLC lesions. METHODS: KAI1/CD82 expression in 200 NSCLC patients who underwent potentially curative surgery was immunohistochemically detected with C33, an anti-KAI1/CD82 monoclonal antibody. According to the degree of KAI1/CD82 positive cancer cells within the tumor tissue, each sample was classified as KAI1/CD82 positive, KAI1/CD82 reduced, or KAI1/CD82 negative. RESULTS: Sixty-five samples (32.5%) were KAI1/CD82 positive, 31 (15.5%) were reduced, and 104 (52%) were negative. There was no significant association between KAI1/CD82 expression and clinicopathologic factors, but patients who were positive for KAI1/CD82 expression had significantly favorable prognoses for overall survival (P = 0.0026) and disease free survival (DFS; P = 0.0007) compared with the other groups. In particular, among patients with adenocarcinoma, similar results were even more significant. In multivariate analysis, immunohistochemical KAI1/CD82 expression in patients with NSCLC was an independent prognostic factor for overall survival and DFS; in those with adenocarcinoma, it was an even more valuable factor. In some patients with NSCLC, especially those with adenocarcinoma, KAI1/CD82 expression levels in metastatic lesions were diminished compared with levels of expression in the primary lung lesions. CONCLUSIONS: The immunohistochemically determined level of KAI1/CD82 expression in NSCLC cells within tumor tissue appears to be a favorable prognostic factor for overall survival as well as DFS. The results of this study suggest that decreased KAI1/CD82 expression may be associated with tumor progression and enhanced metastatic potential in some patients with this disease.

Adult↗
PubMed1998

An ancient retrotransposal insertion causes Fukuyama-type congenital muscular dystrophy.

Fukuyama-type congenital muscular dystrophy (FCMD), one of the most common autosomal recessive disorders in Japan (incidence is 0.7-1.2 per 10,000 births), is characterized by congenital muscular dystrophy associated with brain malformation (micropolygria) due to a defect in the migration of neurons. We previously mapped the FCMD gene to a region of less than 100 kilobases which included the marker locus D9S2107 on chromosome 9q31. We have also described a haplotype that is shared by more than 80% of FCMD chromosomes, indicating that most chromosomes bearing the FCMD mutation could be derived from a single ancestor. Here we report that there is a retrotransposal insertion of tandemly repeated sequences within this candidate-gene interval in all FCMD chromosomes carrying the founder haplotype (87%). The inserted sequence is about 3 kilobases long and is located in the 3' untranslated region of a gene encoding a new 461-amino-acid protein. This gene is expressed in various tissues in normal individuals, but not in FCMD patients who carry the insertion. Two independent point mutations confirm that mutation of this gene is responsible for FCMD. The predicted protein, which we term fukutin, contains an amino-terminal signal sequence, which together with results from transfection experiments suggests that fukutin is a secreted protein. To our knowledge, FCMD is the first human disease to be caused by an ancient retrotransposal integration.

Amino Acid Sequence↗
PubMed1998

Mutations in exon 7 and 8 of p53 as poor prognostic factors in patients with non-small cell lung cancer.

This study was performed to clarify the different effects of each mutant exon of p53 as indicators of a poor prognosis in patients with non-small cell lung cancer (NSCLC). Tumor tissues of 204 patients with NSCLC were analysed; 96 tumors were stage I, 22 stage II, and 86 stage III. DNA was extracted from frozen specimens and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were performed to investigate mutations of p53 from exon 5 to exon 8. Seventy-five patients with NSCLC (36.8%) had mutations in p53 which included 72 cases of missense mutations and three cases of non-missense mutations. The overall survival rate of patients with mutant p53 adenocarcinomas was strikingly worse than that of patients whose tumors had wild-type p53 (35.7% vs 53.8%; P=0.041), but no significant difference in survival was found in the patients with NSCLC and squamous cell carcinoma. Mutations in exon 5 of p53 occurred in 33 cases (16.2%), mutation in exon 6 was detected in only one case (0.5%), mutations in exon 7 in 20 cases (9.8%), and mutations in exon 8 in 18 cases (8.8%). The overall survival rate of patients with mutations in exon 7 was worse than that of patients with wild-type p53 in NSCLCs and adenocarcinomas (42.9% vs 56.0%; P=0.025 and 33.3% vs 53.8%; P=0.048, respectively), whereas the overall survival of patients with mutations in exon 5 was almost the same as that of patients with wild-type p53. In addition, the overall survival rate of patients with mutations in exon 8 was strikingly worse than that of patients with wild-type p53 in NSCLCs, adenocarcinomas and squamous cell carcinomas (22.9% vs 56.0%; P<0.001, 19.0% vs 53.8%; P=0.004 and 33.3% vs 62.5%; P=0.042, respectively). Multivariate analysis with the Cox regression model of patients with NSCLC, adenocarcinoma and squamous cell carcinoma indicated that mutations in exon 8 were best correlated with the overall survival rate, followed by lymph node status (P<0.001, P=0.015 and P=0.006, respectively), and mutations in exon 7 of NSCLC were also revealed to have good correlation, followed by lymph node status and mutations in exon 8 (P=0.031). Mutation of p53 was a poor prognostic factor for adenocarcinoma as described previously. Moreover, mutations in exon 8 were more useful indicators of prognosis not only for adenocarcinoma but also for NSCLC. Worse overall survival of the patients with mutations in exon 8 of p53 was suggested to be associated with codon 273 mutations as well as mutations between codon 280 and 285 included into the H2 alpha helix corresponding to residues 278-286. These results suggested that abnormal conformation of H2 alpha helix might play an important role not only in the loss of normal function but also in the acquisition of tumorigenesis. Investigation of mutations in exon 8, especially codon 273 mutation and mutant H2 alpha helix was considered to be a clinically useful approach for determining the prognosis of patients with NSCLC.

Adenocarcinoma↗
PubMed1998

Vi-deficient and nonfimbriated mutants of Salmonella typhi agglutinate human blood type antigens and are hyperinvasive.

We generated nonfimbriated mutants from both Vi-positive and -negative Salmonella typhi to analyze the role of type 1 fimbriae and Vi-antigen in bacterial invasion. A Vi-defective mutant of S. typhi GIFU 10007-3 was more invasive than the wild-type strain GIFU 10007. The wild-type strain expressing Vi-antigen did not agglutinate both Saccharomyces cerevisiae and human erythrocytes but Vi-defective mutants were able to agglutinate S. cerevisiae and human erythrocytes. Nonfimbriated mutants from Vi-negative GIFU 10007-3 lost the ability to adhere to S. cerevisiae but still could agglutinate human erythrocytes. The Vi-negative mutant increased secreted proteins and became 5-fold more invasive than the wild-type strain. Nonfimbriated Vi mutants became 50-120-fold more invasive than the wild-type GIFU 10007. To determine why nonfimbriated Vi mutants still agglutinate human red blood cells, we searched bacterial proteins that could bind human blood-type antigens. We finally identified a candidate 37 kDa outer membrane protein that recognized fucosyl-galactose, a structure common to blood type A, B and H antigens.

ABO Blood-Group System↗
PubMed1998

Salmonella typhi rpoS mutant is less cytotoxic than the parent strain but survives inside resting THP-1 macrophages.

Transcription of the stationary-phase sigma factor RpoS of Salmonella typhi increased in the macrophage. A single rpoS mutant of S. typhi was constructed to analyze the role of RpoS in intracellular multiplication of the bacterium and host cell killing. This mutant was sensitive to starvation, low pH and hydrogen peroxide; however, it could still multiply inside resting macrophages and was less cytotoxic than the wild-type strain. Therefore, S. typhi might produce RpoS-dependent factors which could contribute to host cell death.

Bacterial Proteins↗
PubMed1998

IgG anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in Guillain-Barré syndrome.

To investigate the pathophysiological role of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we reviewed sequential nerve conduction studies of 345 nerves in 34 GBS patients. Statistically significant correlation between IgG anti-GM1 antibodies and electrodiagnoses was found. Sixteen IgG anti-GM1-positive patients were classified as having acute motor or acute motor sensory axonal neuropathy (AMAN or AMSAN) (12 patients), as having acute inflammatory demyelinating polyneuropathy (AIDP) (3 patients), or as undetermined (1 patient) by electrodiagnostic criteria. Besides axonal features, there was rapid resolution of conduction slowing and block. In 3 patients initially diagnosed as having AIDP, conduction slowing was resolved within days, and 1 of them and 3 AMAN patients showed markedly rapid increases in amplitudes of distal compound muscle action potentials that were not accompanied by prolonged duration and polyphasia. The time courses of conduction abnormalities were distinct from those in IgG anti-GM1-negative AIDP patients. Rapid resolution of conduction slowing and block, and the absence of remyelinating slow components, suggest that conduction failure may be caused by impaired physiological conduction at the nodes of Ranvier. Reversible conduction failure as well as axonal degeneration constitutes the pathophysiological mechanisms in IgG anti-GM1-positive GBS. In both cases, immune-mediated attack probably occurs on the axolemma of motor fibers.

Adult↗
PubMed1998

Separation and enrichment of the active component of carbon based paramagnetic materials for use in EPR oximetry.

Carbon based paramagnetic materials are frequently used for EPR oximetry, especially in vivo, but the EPR spectra of these materials often have more than one paramagnetic center and/or relatively low signal intensity. To determine whether the multi-components of carbon based materials could be separated and enriched in the active component, we used density gradient centrifugation to separate the materials into several fractions. We studied two types of coals, gloxy and Pocahontas, and found these materials to have large density distribution. The separated density fractions had very different EPR spectra and intensities. The active component from the coal material had a more homogeneous EPR signal and significantly increased EPR signal intensity, whereas for India ink, only slight changes were observed. This result can be very useful in the development of better probes for EPR oximetry.

Carbon↗
PubMed1998

Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-D-glucose using whole-body positron emission tomography and magnetic resonance imaging.

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after intravenous administration of 2-[F-18]fluoro-2-deoxy-D-glucose (18F-FDG) using whole-body positron emission tomography (PET) and magnetic resonance imaging (MRI). Whole-body dynamic emission scans for 18F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method using S-values adjusted to the individuals. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the "Japanese reference man" to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1x10(-1), 3.7x10(-2) and 2.8x10(-2) mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9x10(-2) mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1x10(-2) mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered 18F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals.

Adult↗
PubMed1998

Estimation of internal absorbed dose of L-[methyl-11C]methionine using whole-body positron emission tomography.

L-[Methyl-11C]-methionine (11C-methionine) is proposed as a useful radiotracer for tumour diagnosis. Human biodistribution data of cumulated activities and absorbed doses estimated by the MIRD (medical internal radiation dosimetry) method for 11C-methionine are not available in the literature. In this study we measured the organ activity for 11C-methionine by using whole-body positron emission tomography (PET) and estimated the absorbed doses to 25 organs by the MIRD method. Whole-body dynamic PET scans were performed on five normal volunteers to measure the time course of the organ activity concentration (activity/volume) after intravenous administration of 11C-methionine. Cumulated activities of the ten source organs were calculated from the time-activity curves, obtained from the dynamic PET data. Absorbed dose estimates were performed by the MIRD method for the Caucasian reference man and for the Japanese reference man. The organs which received the highest absorbed doses for the Caucasian reference man were found to be the bladder wall (2.7x10(-2) mGy/MBq), the pancreas (1.9x10(-2) mGy/ MBq), the liver (1.8x10(-2) mGy/MBq) and the kidney (1.1x10(-2) mGy/MBq). The effective doses for the Caucasian reference man and the Japanese reference man were calculated as 5.2x10(-3) and 5.0x10(-3) mSv/MBq, respectively.

Adult↗
PubMed1998

Founder-haplotype analysis in Fukuyama-type congenital muscular dystrophy (FCMD).

Fukuyama-type congenital muscular dystrophy (FCMD) is an autosomal recessive, severe muscular dystrophy associated with brain anomalies. After our initial mapping of the FCMD locus to 9q31-33, we performed linkage disequilibrium analysis, which led us to suspect that the FCMD gene lay within a region of less than 100 kb containing D9S2107. In the present study, we developed two new microsatellites (D9S2170 and D9S2171) in close vicinity to D9S2107 and examined haplotypes of FCMD chromosomes by using four markers (cen-D9S2105-D9S2170-D9S2171-D9S2107-tel). As 82% of the FCMD chromosomes that we examined shared the founder haplotype (138-192-147-183) and 94% of the FCMD patients in our panel carried founder haplotypes on one or both chromosomes, the data supported the hypothesis of a single founder of this disease in the Japanese population. Eight haplotypes different from the founder's were observed in FCMD chromosomes, indicating that eight different FCMD mutations in addition to the founder's have occurred in Japan. Moreover, we have detected several historical recombinations that have disrupted the founder haplotype at D9S2105 or D9S2170 and conclude that the FCMD gene is probably located just centromeric to D9S2170.

Chromosomes, Human, Pair 9↗
PubMed1998

Metal-ion stimulation and inhibition of lysophospholipase D which generates bioactive lysophosphatidic acid in rat plasma.

We found that lysophospholipase D (LPLD) in rat plasma prefers unsaturated to saturated lysophosphatidylcholines as substrates, generating a biologically active lipid, lysophosphatidic acid, but it does not hydrolyze diacyl-phospholipids. In this study, this LPLD required a metal ion for activity, Co2+ being the most effective, followed in order by Zn2+, Mn2+, and Ni2+. This metal-ion-stimulated LPLD with unique substrate specificity, which has not been described previously, was susceptible to thiol-blocking reagents and serine esterase inhibitors, but not to a histidine-modifying reagent. Consistent with results using thiol-modifying agents, short-chain fatty aldehydes, secondary products of lipid peroxidation, were found to inhibit LPLD. Addition of dibutylhydroxytoluene or butylhydroxyanisole to the plasma increased the activity of this enzyme, probably in a manner independent of its antioxidant activity, since another antioxidant, propyl gallate, was rather inhibitory. These results suggest that rat plasma contains an active LPLD that differs in some properties from other members of the known phospholipase D family detected in animal tissues and body fluids.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1998

Correlation of reduction in MRP-1/CD9 and KAI1/CD82 expression with recurrences in breast cancer patients.

MRP-1/CD9, KAI1/CD82, and ME491/CD63, have been reported to be associated with the metastatic potential of solid tumors. The aim of this study was to determine whether their expression in tumor tissues is a useful indicator for prognosis in breast cancer patients. We studied 109 breast cancer patients who underwent surgery. Quantitative reverse transcription-polymerase chain reaction analysis was performed to evaluate the expression of these genes. The results were confirmed with immunohistochemistry. All of the carcinomas were ME491/CD63 positive. Thirty-six tumors were MRP-1/CD9 negative. The disease-free survival rate and the 5-year survival rate of patients with MRP-1/CD9-negative tumors were both significantly lower than that in patients with MRP-1/ CD9-positive tumors (P = 0.0005 and P = 0.0380, respectively). Sixty-five tumors were KAI1/CD82 negative. The disease-free survival rate of patients with KAI1/CD82-negative tumors was significantly lower than that of patients with KAI1/CD82-positive tumors (P = 0.0065). Cox regression analysis demonstrated that MRP-1/CD9 status (P = 0.0016) and KAI1/CD82 status (P = 0.0234) were useful indicators for the disease-free survival of breast cancer patients. The disease-free survival rate and 5-year survival rate of patients with either MRP-1/CD9-negative or KAI1/CD82-negative tumors were both significantly lower than patients who were positive for both genes (P = 0.0003 and P = 0.0292, respectively). The expression of MRP-1/CD9 and KAI1/CD82 genes are useful indicators of a poor prognosis in breast cancer patients.

Aged↗
PubMed1998

Mutational analysis of the N-ras gene in acute lymphoblastic leukemia: a study of 125 Japanese pediatric cases.

A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

Child↗
PubMed1998

Design and evaluation of an osmotic pump tablet (OPT) for prednisolone, a poorly water soluble drug, using (SBE)7m-beta-CD.

PURPOSE: The purpose of this study was to develop a controlled-porosity osmotic pump tablet (OPT) for poorly water soluble drugs using a sulfobutyl ether-beta-cyclodextrin, (SBE)7m-beta-CD or Captisol, which acted as both a solubilizer and as an osmotic agent. METHODS: Prednisolone (PDL) was chosen as a model drug for this study. The release of PDL from osmotic pump devices and tablets was studied. In vivo absorption of PDL from OPT was evaluated in male beagle dogs. RESULTS: PDL release from the osmotic pump tablet with (SBE)7m-beta-CD was complete. Another cyclodextrin, hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and a sugar mixture of lactose and fructose resulted in incomplete release. Although PDL release from the OPT with (SBE)7m-beta-CD and the sugar formulation displayed mainly zero-order release characteristics, the tablet utilizing HP-beta-CD showed apparent first-order release characteristics. An in vivo absorption study in dogs correlated very well with the in vitro release profiles using the Japanese Pharmacopoeia dissolution method. CONCLUSIONS: The present results confirm that (SBE)7m-gamma-CD can serve as both the solubilizer and the osmotic agent for OPT of PDL, and modify the input rate of PDL without compromising oral bioavailability.

Absorption↗
PubMed1998

Interleukin 6 and its relationship to clinical parameters in patients with malignant pleural mesothelioma.

The relationship between interleukin 6 (IL-6) levels and clinical parameters was studied in 25 patients with malignant pleural mesothelioma. The serum levels of IL-6, C-reactive protein, alpha1-acid glycoprotein and fibrinogen were significantly higher in mesothelioma than in lung adenocarcinoma with cytology-positive pleural effusion. Serum IL-6 levels correlated with the levels of the acute-phase proteins. We demonstrated a high incidence of thrombocytosis (48%) and a significant correlation between platelet count and the serum IL-6 level. The level of IL-6 in the pleural fluid of patients with mesothelioma was significantly higher than in the pleural fluid of patients with adenocarcinoma, and was about 60-1400 times higher than in the serum. However, even higher levels of IL-6 in the pleural fluid and of thrombocytosis were found in patients with tuberculous pleurisy. These results indicate that large amounts of IL-6 from the pleural fluid of patients with mesothelioma leak into the systemic circulation and induce clinical inflammatory reactions. These profiles are not specific to mesothelioma as similar profiles are found in patients with tuberculous pleurisy. However, the detection of a markedly increased level of IL-6 in pleural fluid argues against a diagnosis of adenocarcinoma.

Adenocarcinoma↗
PubMed1998

Late-onset unilateral renal dysfunction combined with non-insulin-dependent diabetes mellitus and bronchial asthma following allogeneic bone marrow transplantation for acute lymphoblastic leukemia in a child.

We report a child with T cell acute lymphoblastic leukemia who developed late-onset multiple complications after allogeneic bone marrow transplantation from an HLA-matched sibling. The preparative regimen consisted of total body irradiation (TBI, 12 Gy), splenic irradiation (6 Gy) and cytosine arabinoside (3 g/m2 x 10). Splenic irradiation was added because of persistent splenomegaly in spite of intensive chemotherapy. He developed bronchial asthma 1 1/2 years post transplant. He presented with microhematuria and proteinuria 4 1/2 years post-transplant, which were due to unilateral left renal dysfunction. He developed type II, non-insulin-dependent diabetes mellitus 8 years post-transplant. A biopsy from the left kidney was not compatible with diabetic nephropathy. All these complications appear to be independently related to BMT, particularly TBI and/or splenic irradiation.

Adolescent↗
PubMed1998

Effects of calcium and bicarbonate on head-to-head agglutination in ejaculated boar spermatozoa.

The present study was conducted to reveal the effects of calcium and bicarbonate on the occurrence of head-to-head agglutination in ejaculated boar spermatozoa in vitro. Boar spermatozoa were washed and incubated in a modified Krebs-Ringer bicarbonate (mKRB) in a 37 degrees C CO2 incubator (5% CO2 in air) for 1-5 h. Before and after the incubation, aliquots of each sperm sample were fixed, smeared on glass slides, and stained with a phosphate-buffered solution of Giemsa to assess the percentages of head-to-head agglutinated spermatozoa. Before the incubation, only 5-12% of the spermatozoa were agglutinated. After the 1-h incubation, however, the percentage of head-to-head agglutinated spermatozoa rose to approximately 50%, followed by only minor increases thereafter. This rise was dependent on the concentrations of calcium chloride contained in the mKRB and was attenuated by the addition of 2 mM [ethylenebis(oxyethylenenitrilo)]tetra-acetic acid (EGTA) to the medium. Moreover, the replacement of sodium bicarbonate with 2-[4-(2-hydroxyethyl)-1-piperazinyl]ethanesulfonic acid (Hepes) in the medium and treatment with ruthenium red, which have both been shown previously to inhibit calcium uptake by boar spermatozoa, significantly reduced the rise. Based on these findings, it was concluded that extracellular calcium and bicarbonate are key factors regulating head-to-head agglutination in boar spermatozoa. The possible relationship between agglutinability and the fertilizing ability of boar spermatozoa is also discussed.

Animals↗