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Biomedical subjects

J Adachi

Publications and source records attributed to J Adachi.

At least 91 records · Page 5Linked to original sources

Microsatellite instability in primary and metastatic lung carcinomas.

Fifty-seven primary lung carcinomas and 35 metastatic lung carcinomas were analyzed for microsatellite instability at II different chromosomal loci. Although no instability was detected in 37 small cell lung carcinomas (SCLC), it was frequently detected in non-small cell lung carcinomas (NSCLC) (16/55, 29%). In NSCLC, the incidence of replication errors (RERs) in metastatic tumors (12/22, 55%) was significantly higher than that in primary tumors (4/33, 12%) (P = 0.0021). Among 10 pairs of primary tumors and corresponding metastases, there were 4 cases which manifested the identical RER phenotypes in both primary and metastatic tumors. In two cases, RER phenotypes were detected in metastatic but not in primary tumors. Never was an RER phenotype found only in a primary tumor but not in the metastases. RERs were detected more frequently in stage III or IV tumors (3/8, 38%) than stage I or II tumors (1/25, 4%) (P = 0.0359). Tumor cells with allelic losses on chromosome arm 3p or 18q tended to have RER phenotypes (P = 0.0432 and P = 0.0187, respectively). The data suggest that microsatellite instability is common in NSCLC but not in SCLC, and that genomic instability appears late in tumor progression and plays an important role in the acquisition of more malignant phenotypes in NSCLC.

Carcinoma, Non-Small-Cell Lung↗

Improved dating of the human/chimpanzee separation in the mitochondrial DNA tree: heterogeneity among amino acid sites.

The internal branch lengths estimated by distance methods such as neighbor-joining are shown to be biased to be short when the evolutionary rate differs among sites. The variable-invariable model for site heterogeneity fits the amino acid sequence data encoded by the mitochondrial DNA from Hominoidea remarkably well. By assuming the orangutan separation to be 13 or 16 Myr old, a maximum-likelihood analysis estimates a young date of 3.6 +/- 0.6 or 4.4 +/- 0.7 Myr (+/- 1 SE) for the human/chimpanzee separation, and these estimates turn out to be robust against differences in the assumed model for amino acid substitutions. Although some uncertainties still exist in our estimates, this analysis suggests that humans separated from chimpanzees some 4-5 Myr ago.

Amino Acid Sequence↗

Accumulation of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in blood and organs of the Lewis rats.

3-(Phenylamino)alanine (PAA), a newly discovered impurity in case-associated L-tryptophan tablets, has been investigated as a possible contributing factor in the etiology of eosinophilia-myalgia syndrome (EMS). We have studied distribution and elimination of PAA in rats which were administered a single 5 mg/kg dose of PAA by gastric gavage. PAA concentrations in blood, brain, kidney and liver were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. The concentration of PAA in each tissue reached a maximum at 5 h, and then gradually declined. A high level of PAA still remained at 24 h, indicating gradual elimination. The concentration of PAA in brain at 5 h was 2139 ng/g tissue, demonstrating passage through the blood-brain barrier. Consecutive administration of PAA (5 mg/kg) for 4 days resulted in approximately double the concentration in all tissues. Chronic treatment using PAA incorporated into food pellets for 6 weeks resulted in similar accumulations in each tissue, and following 12 days on a PAA free diet, levels of this drug were still detectable in all tissues.

Alanine↗

Phylogenetic place of mitochondrion-lacking protozoan, Giardia lamblia, inferred from amino acid sequences of elongation factor 2.

Partial regions of the mRNA encoding a major part of translation elongation factor 2 (EF-2) from a mitochondrion-lacking protozoan, Giardia lamblia, were amplified by polymerase chain reaction, and their primary structures were analyzed. The deduced amino acid sequence was aligned with other eukaryotic and archaebacterial EF-2's, and the phylogenetic relationships among eukaryotes were inferred by the maximum likelihood (ML) and the maximum parsimony (MP) methods. The ML analyses using six different models of amino acid substitutions and the MP analysis consistently suggest that among eukaryotic species being analyzed, G. lamblia is likely to have diverged from other higher eukaryotes on the early phase of eukaryotic evolution.

Amino Acid Sequence↗

Developmental ability of zona-free mouse embryos is influenced by cell association at the 4-cell stage.

Zona-free embryos at the 4-cell stage were classified into four types according to the total points of contact between the 4 blastomeres. Types A, B, C, and D had 3, 4, 5, and 6 points of contact, respectively. Embryos of these types were cultured individually in 20 microliters of Whitten's medium. Blastocysts derived from types A and D embryos at the 4-cell stage were transferred and observed on Day 17 of gestation. The number of live fetuses was significantly lower for type A than for type D embryos (p < 0.05). In spite of the removal of the zone pellucida, both types A and D blastocysts had cell numbers similar to those in zona-intact control embryos at 96 h after insemination. However, type A embryos had fewer (p < 0.05) inner cell mass (ICM) cells than did either the zona-intact control or type D embryos. Type D embryos did not have significantly fewer ICM than did the zona-intact control. Our data show that the cell association of zona-free embryos at the 4-cell stage influences differentiation of cells within the ICM and thus affects subsequent embryonic development. We suggest that one role of the zona pellucida after fertilization, in addition to protecting the preimplantation embryo, is to maintain the cell arrangement of 4-cell stage embryos to ensure subsequent successful cell lineage.

Animals↗

Diagnosis of brainstem abscess in the cerebritis stage by magnetic resonance imaging--case report.

A 52-year-old male presented with a brainstem abscess manifesting as high fever, diplopia, and left hemiparesis. Magnetic resonance (MR) imaging with gadolinium diethylenetriamine pentaacetic acid showed the lesion as a ring-like enhanced mass consisting of a necrotic center with surrounding edema, whereas postcontrast computed tomography revealed no such confirmatory findings. He was treated with antibiotics as the lesion had been detected in the acute cerebritis stage. Serial MR images showed that the lesion decreased remarkably in size. MR imaging can detect brain abscess in the earliest inflammatory stage.

Acute Disease↗

Functioning of the intrathoracic stomach after esophagectomy.

OBJECTIVE: To investigate acid secretion and motility of the intrathoracic stomach with truncal vagotomy after esophagectomy. DESIGN: Case-control study of patients undergoing esophagectomy, with average follow-up of 3.2 months, compared with health controls. SETTING: Yamaguchi University School of Medicine, Kogushi, Japan. PATIENTS: A random sample of 21 patients selected from 79 patients with esophageal cancer during the period from May 1988 to August 1993 received the intrathoracic stomach after subtotal esophagectomy. A control sample consisted of 14 men. INTERVENTIONS AND MAIN OUTCOME MEASURES: For acid secretion, a pH probe was placed in the intrathoracic stomach to measure the average pH value (average of total monitoring values) and pH holding time (ratio of the period during which the pH value was 3 or higher based on the entire continuous monitoring periods). For motility, digestive tract scintigraphy was performed to obtain the time activity curve from the analog image observed when patients ate meals labeled with indium 111. In addition, hemorrhagic ulcers in the intrathoracic stomachs of three patients were reported. RESULTS: A pH value below 3 was recognized after surgery, and there was no significant difference between pH values in patients and normal volunteers (average pH value, 3.9 +/- 1.5 vs 3.3 +/- 1.9; pH holding time, 52.2 +/- 20.2% vs 57.1 +/- 24.4%, respectively). The time activity curve of the intrathoracic stomach observed by scintigraphy underwent no change after surgery. Among three patients with hemorrhagic ulcers, two exhibited improvements after receiving a histamine blocker, while in the other, it was not effective. CONCLUSION: Acid secretion ability and motility of the intrathoracic stomach with truncal vagotomy may be unchanged after esophagectomy.

Case-Control Studies↗

Phylogenetic relationships among eutherian orders estimated from inferred sequences of mitochondrial proteins: instability of a tree based on a single gene.

The phylogenetic relationships among Primates (human), Artiodactyla (cow), Cetacea (whale), Carnivora (seal), and Rodentia (mouse and rat) were estimated from the inferred amino acid sequences of the mitochondrial genomes using Marsupialia (opossum), Aves (chicken), and Amphibia (Xenopus) as an outgroup. The overall evidence of the maximum likelihood analysis suggests that Rodentia is an outgroup to the other four eutherian orders and that Cetacea and Artiodactyla form a clade with Carnivora as a sister taxon irrespective of the assumed model for amino acid substitutions. Although there remains an uncertainty concerning the relation among Artiodactyla, Cetacea, and Carnivora, the existence of a clade formed by these three orders and the outgroup status of Rodentia to the other eutherian orders seems to be firmly established. However, analyses of individual genes do not necessarily conform to this conclusion, and some of the genes reject the putatively correct tree with nearly 5% significance. Although this discrepancy can be due to convergent or parallel evolution in the specific genes, it was pointed out that, even without a particular reason, such a discrepancy can occur in 5% of the cases if the branching among the orders in question occurred within a short period. Due to uncertainty about the assumed model underlying the phylogenetic inference, this can occur even more frequently. This demonstrates the importance of analyzing enough sequences to avoid the danger of concluding an erroneous tree.

Animals↗

Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.

3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6 micrograms between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Administration, Oral↗

Demonstration of sweat allergy in cholinergic urticaria.

Twenty patients with cholinergic urticaria, 11 sex- and age-unmatched patients with acute or chronic urticaria and 20 sex- and age-matched non-atopic control subjects were skin tested with autologous sweat. All cholinergic urticaria patients showed positive immediate-type skin reactions at 2(0)-2(9) dilutions of sweat (geometric mean of maximal positive dilutions +/- S.D. was 2(4.6 +/- 2.6), while in acute and chronic urticaria only three patients showed positive reactions at low dilutions (two 2(0) and one 2(1)) and none of 20 controls showed positive reactions. Prausnitz-Küstner (P-K) tests performed with the serum and sweat from six patients were all positive at 2(3)-2(8) dilutions. Percent histamine release from peripheral leukocytes of five patients challenged with the standard sweat samples was significantly higher than in five control subjects. Histamine release from leukocytes of the patient on sweat challenging was abandoned by acid treatment of leukocytes. Leukocytes, from a healthy subject sensitized with the patient's serum, released histamine on sweat challenging. These results seem to indicate that cholinergic urticaria patients have a type I allergy to their own sweat.

Adolescent↗

Protein phylogeny gives a robust estimation for early divergences of eukaryotes: phylogenetic place of a mitochondria-lacking protozoan, Giardia lamblia.

A partial nucleotide sequence of the mRNA encoding a major part of elongation factor 1 alpha (EF1 alpha) from a mitochondria-lacking protozoan, Giardia lamblia, was reported, and the phylogenetic relationship among lower eukaryotes was inferred by the maximum-likelihood and maximum-parsimony methods of protein phylogeny. Both the methods consistently demonstrated that, G. lamblia among the four protozoan species being analyzed, is the earliest offshoot of the eukaryotic tree. Although the Giardia EF1 alpha gene showed an extremely high G+C content as compared with those of other protozoa, it was concentrated only at the third codon positions, resulting in no remarkable differences of amino acid frequencies vis-à-vis those of other species. This clearly suggests (a) that the amino acid frequencies of conservative proteins are free from the drastic bias of genome G+C content, which is a serious problem in the widely used tree of ribosomal RNA, and (b) that protein phylogeny gives a robust estimation for the early divergences in the evolution of eukaryotes.

Amino Acid Sequence↗

Phylogenetic place of guinea pigs: no support of the rodent-polyphyly hypothesis from maximum-likelihood analyses of multiple protein sequences.

Graur et al.'s (1991) hypothesis that the guinea pig-like rodents have an evolutionary origin within mammals that is separate from that of other rodents (the rodent-polyphyly hypothesis) was reexamined by the maximum-likelihood method for protein phylogeny, as well as by the maximum-parsimony and neighbor-joining methods. The overall evidence does not support Graur et al.'s hypothesis, which radically contradicts the traditional view of rodent monophyly. This work demonstrates that we must be careful in choosing a proper method for phylogenetic inference and that an argument based on a small data set (with respect to the length of the sequence and especially the number of species) may be unstable.

Animals↗

Phylogenetic place of a mitochondria-lacking protozoan, Entamoeba histolytica, inferred from amino acid sequences of elongation factor 2'.

Partial DNA regions encoding a major part of translation elongation factor 2 (EF-2) from a mitochondria-lacking protozoan, Entamoeba histolytica, were amplified by polymerase chain reaction and their primary structures were analyzed. The deduced amino acid sequence was aligned with other eukaryotic and archaebacterial EF-2's, and the phylogenetic relationships among eukaryotes were inferred by the maximum likelihood (ML) method. The ML analyses using four different stochastic models of amino acid substitutions consistently suggest that among eukaryotic species being analyzed, E. histolytica is likely to have diverged from other higher eukaryotes on the early phase of eukaryotic evolution.

Amino Acid Sequence↗

Eutherian phylogeny as inferred from mitochondrial DNA sequence data.

The phylogenetic relationships among Primates, Artiodactyla, Cetacea, Carnivora, and Rodentia were estimated from the amino acid sequences of proteins encoded by the mitochondrial genomes, for which entire nucleotide sequence data are available, using Marsupialia, Aves, and Amphibia as outgroups. The overall evidence of the maximum likelihood, as well as maximum parsimony, analyses strongly suggests that Rodentia is an outgroup to the other four eutherian orders, and that Cetacea and Artiodactyla form a clade with Carnivora as a sister taxon, consistently with the molecular phylogenetic studies of previous authors. However, analyses of individual proteins do not necessarily conform to this conclusion, and some of the proteins reject the putatively correct tree with nearly 5% significance. Furthermore, the 12S mitochondrial ribosomal RNA sequences do not give the putatively correct tree irrespective of the alignments and of the phylogenetic methods, although the tree is not rejected with a statistical significance. The 16S ribosomal RNA sequences give the putatively correct tree with our sequence alignment when the ML method is used, but the result depends on the alignment and on the choice of outgroup species. These results illustrate the limitation of the ribosomal RNA data alone in phylogenetic inference, and suggest that we must analyze as many genes as possible and synthesize the results to draw a reliable conclusion.

Amino Acid Sequence↗

Intermittent cyclic therapy with etidronate in the prevention of corticosteroid induced bone loss.

OBJECTIVE: To assess the potential efficacy of intermittent cyclic therapy (ICT) with etidronate in the treatment of patients with corticosteroid induced osteoporosis. METHODS: Cohort study in a tertiary care university affiliated hospital in corticosteroid treated patients, with polymyalgia rheumatica, asthma, systemic lupus erythematosus, rheumatoid arthritis, or temporal arteritis, examining the effects of ICT etidronate. Patients were included if they were taking corticosteroids for a minimum of one year. Comparison patients were those who had been taking corticosteroids for a minimum of one year and who had not been treated with etidronate or other medication which might alter bone metabolism. A total of 68 patients were included from 253 considered. The mean (SD) dose of prednisone in the ICT etidronate treated patients was 9.3 (6.2) mg and in the comparison patients 9.4 (5.9) mg. The duration of prednisone therapy was 7.8 (5.8) years and 3.4 (4.2) years, respectively (p2 < 0.001). An analysis of covariance demonstrated that this difference did not alter our primary outcome measure. The primary outcome measure was the difference in the percentage change from baseline to one year of followup in bone mineral density (BMD) of the lumbar spine between treatment and comparison groups. RESULTS: ICT etidronate resulted in a statistically significant and clinically important increase in BMD. The BMD of the lumbar spine increased by 3.82% (0.65%), [95% confidence interval (CI), 2.51 to 5.14%] in the 35 ICT etidronate treated patients and decreased by 1.78% (0.76%), [95% CI, -3.34 to -0.23%] in the 33 comparison patients after 12 months (p2 < 0.0001). CONCLUSIONS: ICT etidronate prevented loss of vertebral bone density in patients with corticosteroid induced osteoporosis. Controlled, double blind, prospective trials with longer followup are needed to confirm these results and to demonstrate that increases in bone mass translate into decreased fracture rates.

Adrenal Cortex Hormones↗