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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 739 records · Page 41Linked to original sources

[Effect of body weight reduction on blood pressure and biochemical data].

The purpose of this study was to investigate the relation between body weight reduction and some complications associated with obesity. The subjects were 248 middle-aged obese persons (male 37, female 209) who participated in a weight reduction program at the Aichi Prefectural Center of Health Care from 1983 to 1990. The subjects had no severe complication, and the obesity indexes of all of them were over 120%. The program was held monthly for five months and consisted of diet (1500 kcal/day) and exercise (10000 walk steps/day). After the program, mean obesity index decreased by about 9%, and mean body weight reduction was about 5kg. Blood pressure, total cholesterol, triglyceride and GPT were significantly decreased, and HDL cholesterol was slightly increased. For each item the percentage of persons with abnormal values reduced by about 5 to 20%. From the relationship between degree of decrease of obesity and changes of the values of each item, it was estimated that some complications of obesity require greater than 5 to 10% decrease in obesity index to be affected. The value of each examination item before the program and the degree of decrease of obesity index had an effect on changes of the values, but obesity index before the program and age had little effect.

Adult↗

[Effect of ritodrine hydrochloride on fetal perfusion pressure in dually perfused human placenta].

Ritodrine hydrochloride is widely used in clinical obstetrics for the prevention of premature labor, but the knowledge of its effect on fetal circulation is limited. The purpose of this study was to elucidate changes in vascular resistance in the fetal placental circulation by using the dually perfused human placenta in vitro. The viability of the perfused placenta was maintained during the experiments because the production rate of hCG was constant. The transfer of ritodrine hydrochloride was observed and its concentration on the fetal side was about one third of maternal side at 120 min subsequent to the injection. The fetal perfusion pressure during the control period was 38.6 +/- 7.0 mmHg (mean +/- S.D., n=3). After the addition of ritodrine hydrochloride to the maternal circulation, the fetal perfusion pressure was decreased dose-dependently. The pressure was 95.4 +/- 1.8% at 80 ng/ml of ritodrine hydrochloride which was within the clinical concentration limits. It is concluded that ritodrine hydrochloride acts as a vasodilator on the fetal vasculature in the human placenta.

Adrenergic beta-Agonists↗

[Validity of photographical dietary assessment; a preliminary analysis].

We estimated nutritional intake from color photographs taken of meals with a 35-mm camera, and compared them with the values calculated from the menu. Among 21 meals examined, the coefficient of correlation between the values by the photo method and those from examining the menu was appreciably high; 0.842 in energy, 0.828-0.931 in three major nutrients, and 0.745-0.940 in vitamins and minerals. The differences between the photo method and menu observation were 0-14.8% on average, and the coefficient of variation of the differences was 9.1-32.3%. Estimation of salt was, however, very poor, and the agreement was lower due to the cooking method used. Some differences were found among the dietitians in estimated values of several nutrients. The running cost was approximately 87-yen per meal, which may pose a problem for large-scale dietary surveys. Compared with the use of record, recall, and frequency questionnaire methods, the photo method was easily used by participants, especially those not used to cooking, and could be applied to eating out or for take-out food. Moreover, this method may provide not only quantitative data but also qualitative including eating atmosphere. When estimation is difficult due to the ingredients or recipe, combined use with record or recall methods can facilitate estimation. This photo method is thus considered to be a valid and feasible means of dietary assessment.

Food Analysis↗

Increased expression of sialyl Lewis A and sialyl Lewis X in liver metastases of human colorectal carcinoma.

Sialyl Lewis A (SLA) and sialyl Lewis X (SLX) have been shown to be specific ligands for endothelial leukocyte adhesion molecule-1 (ELAM-1), and may be involved in the process of adhesion between cancer cells and endothelium. We used immunohistochemical methods to study the expression of SLA, SLX and CEA in both primary tumors and matched metastatic liver lesions of colorectal carcinomas. Specimens from primary tumors and matched liver metastases from 24 patients with colorectal carcinomas were studied immunohistochemically. The degree of expression of CEA in liver metastases was similar to that in primary tumors, but SLA and SLX were expressed on a larger proportion of tumor cells in liver metastases than in primary tumors. Our findings suggest that colorectal carcinoma cells expressing SLA and/or SLX form metastatic liver tumors. They also suggest that expression of SLA and SLX in primary of colorectal carcinoma can be used as a prognostic indicator of metastasis.

Adult↗

Use of strip biopsy for early duodenal cancer--a case report.

A 67-year-old man was referred for investigation of an abdominal mass. Upper gastrointestinal endoscopy revealed a polypoid lesion with a central depression in the duodenum. CT scan demonstrated a cystic lesion anterior to the pancreas. Examination of a biopsy specimen of the duodenal lesion suggested it was a carcinoma. Strip biopsy was therefore performed, and histological examination revealed a tubular adenocarcinoma with invasion limited to the mucosa, indicating that the lesion was completely resected. Subsequent 24-month follow-up did not indicate recurrence of the cancer. Strip biopsy thus appears to be a safe and efficient procedure for the management of early duodenal cancer.

Adenocarcinoma↗

Defective T cells from gld mice play a pivotal role in development of Thy-1.2+B220+ cells and autoimmunity.

The gld mouse represents a fascinating animal model of autoimmune disease, which is characterized by massive development of Thy-1.2+B220+ CD4-CD8- cells. These cells thus have double positive markers for T and B cells, but are double negative for CD4 and CD8 markers and are thus designated DN cells in the present context. An additional important feature in gld mice is a defect in expression of Fas ligand. To investigate the regulatory role of bone marrow-derived cells for the development of these DN cells and of gld autoimmunity, we constructed chimeric mice transplanted with fetal liver cells or fetal thymus from gld mice into nonirradiated severe combined immunodeficient (SCID) mice. These chimeric mice regenerated, developed both these DN cells and the gld autoimmune syndrome and also generalized lymphoproliferative disorders. However, when fetal liver cells from both gld and non-gld mice (C57BL/10 Thy-1.1 mice) were co-transplanted into SCID mice, the development of DN cells was apparently inhibited. Further, this inhibition was also seen in SCID mice that had been grafted with both gld and non-gld fetal thymus revealing the pivotal role played by T cells in development of DN cells. When B cells purified from non-gld (C3H+/+) mice were transplanted into SCID mice grafted with gld fetal thymus, the development of DN cells was not inhibited. Taken together, these findings indicate that T cells from non-gld mice inhibit the expression of gld features, e.g., lymphoproliferation, immune-based nephritic disease, and autoantibody production. These findings also suggest that the Fas ligand is selectively expressed on T cells.

Animals↗

Glycation of human beta 2-microglobulin in patients with hemodialysis-associated amyloidosis: identification of the glycated sites.

beta 2-Microglobulin (beta 2M) is a major component forming amyloid deposits in patients with hemodialysis-associated amyloidosis (HAA), a serious complication of long-term hemodialysis. Recently, we demonstrated that beta 2M modified with the Maillard reaction is a definite constituent of amyloid deposits in patients with HAA. Our further study demonstrated that this modified beta 2M induces not only chemotaxis of monocytes but also secretion of tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 from macrophages, suggesting the potential link of glycation of beta 2M by the Maillard reaction to the pathogenesis of HAA. The present study was undertaken to identify the glycated site(s) of beta 2M purified from long-term hemodialysis patients as well as beta 2M incubated with glucose in vitro. Borotritide-treated beta 2M was cleaved by endoproteinase Lys-C, and peptides were isolated by reverse-phase high-performance liquid chromatography, followed by amino acid sequence analysis and fast atom bombardment mass spectrometry to identify the glycated site. The glycated sites of beta 2M formed in vivo were found to be almost the same as those of glycated beta 2M in vitro. The primary glycated site was the alpha-amino group of the amino terminal isoleucine. Other minor sites were the epsilon-amino groups of Lys-19, -41, -48, -58, -91, and -94. Computer graphics of the three-dimensional structure of beta 2M suggested that the high specificity for the glycated site at Ile-1 may be explained by its high solvent accessibility and the nearby imidazole group of His-31 as an acid-base catalyst of the Amadori rearrangement.

Adult↗

Chemical modification of Penicillium 1,2-alpha-D-mannosidase by water-soluble carbodi-imide: identification of a catalytically important aspartic acid residue.

1,2-alpha-D-Mannosidase from Penicillium citrinum was inactivated by chemical modification with 1-ethyl-3-(3-dimethylamino-propyl)carbodi-imide (EDC). Most of the activity was lost after modification in the absence of a nucleophile, glycine ethyl ester. 1-Deoxymannojirimycin (dMM), a competitive inhibitor of the enzyme, showed partial protection against the inactivation. After the modification by EDC without the presence of a nucleophile, proteolytic digests of the enzyme were analysed by reversed-phase h.p.l.c. and a unique peptide was shown to decrease when dMM was present during the modification. The peptide was absent from the digests of unmodified enzyme. The amino acid sequence of the peptide (A; Ile-Gly-Pro) was identical in part with that of the adjacent peptide (B; Ile-Gly-Pro-Asp-Ser-Trp-Gly-Trp-Asp-Pro-Lys). When cholecystokinin tetrapeptide (Trp-Met-Asp-Phe-NH2) was modified by EDC alone, the modified peptide could be separated from unmodified peptide by reversed-phase h.p.i.c., and Edman degradation was stopped before the modified aspartic acid residue. This suggested that, in the enzyme, peptide A was derived from peptide B by the modification. Consequently, Asp-4 in peptide B was assumed to be masked by dMM during the modification, and to be involved in the interaction of the enzyme with its substrate.

1-Deoxynojirimycin↗

Purification and characterization of a novel arginine-specific cysteine proteinase (argingipain) involved in the pathogenesis of periodontal disease from the culture supernatant of Porphyromonas gingivalis.

A novel arginine-specific cysteine proteinase, termed "argingipain," was purified from culture supernatants of Porphyromonas gingivalis, an anaerobe commonly associated with progressive periodontal disease, by conventional chromatographic techniques. The purified enzyme was found to be composed of a single polypeptide of M(r) approximately 44,000. Analysis of the enzymatic properties revealed several distinctive features for this enzyme. The proteolytic activity is absolutely thiol-dependent, but the enzyme also has in part the characteristics of both metallo and serine endopeptidases, as shown by the inhibition of activity by metal chelators, chymostatin, and the chloromethyl ketones of tosyl-L-lysine and tosyl-L-phenylalanine. However, internal protease inhibitors, such as cystatins, tissue inhibitor of metalloproteinases, and alpha 1-antichymotrypsin, have no effects on the activity, suggesting its evasion from normal host defense systems in vivo. Despite its narrow specificity for synthetic substrates containing Arg in the P1 site and hydrophobic amino acids in the P2 or P3 sites, the enzyme extensively degrades collagens (types I and IV) and immunoglobulin G. Most important, the enzyme has the ability to disrupt the functions of polymorphonuclear leukocytes, as shown by its inhibitory effect on the generation of active oxygen species from the activated cells. Further, the enzyme is found to be produced by all of the species of P. gingivalis examined, but not by other bacteria. These results suggests that argingipain plays a key role as a major virulence factor from P. gingivalis in the development of periodontal disease via the direct destruction of periodontal tissue components and the disruption of normal host defense mechanisms.

Adhesins, Bacterial↗

A gD homologous gene of feline herpesvirus type 1 encodes a hemagglutinin (gp60).

A gene-encoding glycoprotein D (gD) homologue of feline herpesvirus type 1 (FHV-1) was identified and sequenced. It was located within an EcoRI 4.3-kbp fragment in the middle of the unique short region. The primary translation product of the gD homologous gene is predicted to consist of 374 amino acids with a molecular weight (MW) of 43.2 kDa. Comparative analysis among gD counterparts of other herpesviruses revealed that six cysteine residues which correlate with disulfide bond structure were conserved, and the amino acid sequences had homologies of 32.6% with bovine herpesvirus type 1 gIV, 29.1% with pseudorabies virus gp50, 28.3% with equine herpesvirus type 1 gD, and 22.0% with herpes simplex virus type 1 gD. When the gD homologue was expressed in COS cells and examined by indirect immunofluorescence and immunoprecipitation assays, it was recognized only by monoclonal antibodies (MAbs) reactive with gp60 which have virus-neutralizing and hemagglutination (HA)-inhibition (HI) activities. This expressed product had a MW of approximately 60 kDa and was shown to be a hemagglutinin by HA and HI tests with the MAbs. These results suggest that the gD homologue of FHV-1 is a hemagglutinin.

Amino Acid Sequence↗

Alteration in regional brain neuropeptides following intracerebroventricular infusion of excitotoxins in rats.

We determined regional brain concentrations of somatostatin (SS), neuropeptide Y (NPY) and arginine-vasopressin (AVP) in 3- and 13-month-old rats. We also examined the effects of the excitotoxins, ibotenic acid (IA), kainic acid (KA), and quinolinic acid (QA) on regional levels of brain neuropeptides in rats. Excitotoxins were infused continuously into the lateral ventricle for 14 days using an osmotic minipump. Our results indicate that; (1) NPY in the brain is especially vulnerable to aging, compared to AVP. (2) IA induces a decrease in brain regional concentrations of neuropeptides and the effects are different from those of other excitotoxins, for example, KA and QA. (3) These effects of IA on neuropeptides may be dependent on the age of the animals when exposed and on the dose of IA.

Age Factors↗

Beta 2-microglobulin modified with advanced glycation end products induces interleukin-6 from human macrophages: role in the pathogenesis of hemodialysis-associated amyloidosis.

Recently, we demonstrated that beta 2-microglobulin (beta 2M) of amyloid deposits in hemodialysis-associated amyloidosis (HAA), a serious complication leading to hemodialysis arthropathy, is modified with advanced glycation end products (AGEs) of the Maillard reaction. In the present study, to elucidate the possible involvement of AGEs-modified beta 2M (AGE-beta 2M) in the pathogenesis of HAA, we examined the effect of AGE-beta 2M on macrophage production of interleukin-6 (IL-6), an important cytokine for osteoclastogenesis and bone resorption. Purified AGE-beta 2M from long-term hemodialysis patients, but not normal beta 2M, stimulated synthesis and secretion of IL-6 from macrophages. Similar effects were also induced by in vitro-prepared AGE-beta 2M (normal beta 2M incubated with glucose for 60 days in vitro). These findings suggested a potential role of AGE-beta 2M in the pathogenesis of HAA.

Amyloidosis↗

Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by the presence of abnormal subpopulations of blood cells that are deficient in surface expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Recent studies showed that the gene termed PIG-A, which participates in the first step of GPI-anchor biosynthesis, is mutated in the abnormal blood cells from patients with PNH. In this study the genomic PIG-A gene was cloned and characterized to obtain nucleotide sequence information for analyzing somatic mutations of PIG-A in patients with PNH. The PIG-A gene is at least 17 kb long and has six exons. The exon-intron boundaries and 583 bp of the 5' flanking region were sequenced. The 5' flanking region has no TATA-like sequence, but includes four CAAT boxes, two AP-2 sequences, and a CRE sequence, some of which are present in regions necessary for the promoter activity. We report pairs of oligonucleotide primers for polymerase chain reaction that should be useful to amplify and analyze various regions of the PIG-A gene in patients with PNH.

Base Sequence↗

Nucleotide sequence analysis of Marek's disease virus (MDV) serotype 2 homolog of MDV serotype 1 pp38, an antigen associated with transformed cells.

Marek's disease (MD) virus (MDV) serotype 1 (MDV1) pp38, an antigen associated with MD-transformed cells, has been identified as an MDV1 serotype-specific antigen by analyses using specific monoclonal antibodies (MAbs). In the present study, we determined the region in the MDV serotype 2 (MDV2) genome that has homology with the MDV1 pp38 gene. As a result of sequence analysis, it was determined that an open reading frame (ORF) existed in this region. Furthermore, Northern blot analysis and reverse transcriptase polymerase chain reaction confirmed the existence of an RNA transcript related to the ORF in MDV2-infected cells. Computer analyses revealed that MDV1 pp38 could be divided into two parts; one part was highly homologous and the other part was not homologous with the peptides deduced from the ORF of MDV2, indicating that the epitope recognized by a MDV1 pp38-specific MAb is located in the latter part.

Amino Acid Sequence↗

Spontaneous nitric oxide release accounts for the potent pharmacological actions of FK409.

(+-)-(E)-Ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), which was isolated from microbial products, has been reported to show a vasorelaxant effect through a mechanism similar to that of the organic nitrates such as isosorbide dinitrate. In solution at pH 7.4, FK409 decomposed and released nitric oxide (NO) spontaneously, while isosorbide dinitrate did not. In in vitro biological tests, FK409 inhibited norepinephrine-induced contraction in rat isolated aorta more potently than did isosorbide dinitrate (ED50 = 1.0 and 310 nM, respectively) and ADP-induced human platelet aggregation (IC50 = 0.75 and > 100 microM, respectively). Nitrite/nitrate was recovered in urine accumulated for 24 h after collection from rats given FK409 or isosorbide dinitrate (10 mg/kg p.o.). FK409 (10 mg/kg p.o.) increased the plasma cyclic GMP level and at the same time decreased the mean blood pressure in conscious rats, while isosorbide dinitrate (10 mg/kg p.o.) did not change these parameters significantly. These results suggest that FK409 produces these pharmacological actions via spontaneously released NO, unlike isosorbide dinitrate, and has a possibility of becoming a unique orally active drug for cardiovascular diseases as a new NO donor.

Adenosine Diphosphate↗

No enhancement by nitric oxide of glutamate release from P2 and P3 synaptosomes of rat hippocampus.

Effects of nitric oxide on glutamate (Glu) release in long-term potentiation (LTP) were investigated by superfusion of conventional (P2) and large (P3) synaptosomes prepared from the rat hippocampus. Basal releasing rates of endogenous Glu from P2 and P3 fractions were 103.6 and 85.2 pmol/min/mg protein, respectively. Exposure to a depolarizing concentration of KCl (30 mM) evoked 3.58- and 4.52-fold increases in releasing rates of Glu from P2 and P3 fractions, respectively. Although the perfusion with sodium nitroprusside (NP, 10(-3) M), a nitric oxide-releasing agent, failed to augment the K(+)-evoked releases of Glu from P2 and P3 synaptosomes, NP enhanced that from slices of the hippocampus by 39% without changing basal release. Similarly, 8-bromoguanosine 3':5'-cyclic monophosphate (10(-4) M) increased the K(+)-evoked release of Glu from slices by 30%, but not from either synaptosomes. When synaptosomes were prepared from the hippocampus which was pretreated with two trains of electrical field stimulation (100 Hz, 0.1 ms, for 2 s), K(+)-evoked releases of Glu from P2 and P3 synaptosomes were increased by 15% and 23%, respectively. Although nitric oxide is postulated to function as a retrograde messenger to maintain LTP, present results suggest that nitric oxide may not directly act upon nerve terminals to enhance glutamate release, but that interventions of glias and short neurons may be involved in the presynaptic mechanism of LTP.

Amino Acids↗

Identification of mutations in DNA polymerase beta mRNAs from patients with Werner syndrome.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by prematurely aged appearance. Genetic linkage analysis has placed the relevant gene in subchromosomal band 8p12. DNA polymerase beta gene has been mapped to chromosome 8p12-11 and thought to be involved in DNA repair and possibly in recombination. Somatic cells from WS patients exhibit chromosomal instability, a markedly reduced replicative life span and slow growth. The functions of DNA polymerase beta gene and its position prompted us to examine this gene in WS patients. We have found the novel DNA polymerase beta cDNA species in blood samples from WS patients, which contain 107 bp insertions or 87 bp deletions in the catalytic domain of DNA polymerase beta. These mutations change the structure of DNA polymerase beta and thus the capacity of the DNA repair system would be impaired, which may account for the high mutation rate observed in WS.

Amino Acid Sequence↗