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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 433 records · Page 24Linked to original sources

[Advances in molecular biological investigation of blood group-active substances on the human red blood cell].

Blood group antigens on the human red blood cell are originally of serological significance. Recent advances in molecular biology and genetics have greatly increased our knowledge of the chemical structures, functions, and genetic backgrounds of these antigens. Carbohydrate antigens are widely expressed in various tissues, whereas protein(polypeptide) antigens are generally specific to the surface molecules of erythroid cells, suggesting their possible roles in membrane structure and function (transporters, receptors, adhesion molecules, and enzymes). This paper reviewed the recent topics with special regard to clinical significance including blood transfusion, and discussed.

ABO Blood-Group System↗

[Errors in detection of subgroups in the ABO blood group system].

In the ABO blood group system, several subgroups have been described based on: 1) the difference of reactivities of the red cells with anti-A, anti-B, anti-A1, and anti-H, 2) the presence or absence of anti-A, anti-B, anti-A1, anti-H, and anti-HI in serum, and 3) the presence of A, B, H substances in the saliva of ABH secretors. Subgroups of A are more frequent in Caucasians than in Japanese, while those of B are more frequent in Japanese. Both the red cell typing (testing red cells for A and B antigens) and serum typing (testing the antibodies in the serum against red cells of known ABO groups) are important to identify and not to overlook these ABO subgroups. When transfusion is required in individuals with these subgroups, compatible blood products must be selected according to the presence or absence of antibodies active at 37 degrees C.

ABO Blood-Group System↗

[Deleterious pathogenic mechanism involving host response in influenza virus infection in mice].

In the influenza virus infected mice there is a host response which involves free radical generation particularly in the host lung. First, superoxide generation was elevated excessive extent, 200-600 fold in the alveolar lavage fluid (BALF), by induction of xanthine oxidase which becomes maximal at about 8 days after infection while virus yield becomes maximum on day 4. Mice start to die on day 9 although the virus in BALF is undetectable; thus virus disease in the absence of virus. Second, inducible form of nitric oxide synthetase is also triggered exactly in parallel to xanthine oxidase. This indicates NO and O2- is produced simultaneously implicating the formation of peroxynitrite (ONOO-) due to a rapid reaction between NO + O2-. Consequently nitration of lung tissue by ONOO- was demonstrated. ONOO- is also found much toxic than O2- or H2O2 in the cultured cells. Third, proteases are involved in various ways in this infection; activation of xanthine dehydrogenose to xanthine oxidase, activation of viral infectivity and triggering of bradykinin generation and inflammation by activating prekallikrein. Lastly, activation of matrix procollagenase (proMMP) by ONOO- and NO2, generated above, was suggested, which will damage connective tissue. Thus all events involving proteases will augment viral pathogenesis.

Animals↗

[Bronchial hyperresponsiveness in patients with vasospastic angina pectoris (VSAP)].

To determine the relationship between airway and coronary artery spasmogenesity in patients with vasospastic angina pectoris (VSAP), we measured the bronchial responsiveness to inhaled methacholine in 21 VSAP patients (V-group) and compared it to that of 17 chest pain syndrome patients with normal coronary (N-group). In the V-group, logarithmic values of the minimum cumulative dose required to decrease respiratory conductance from the baseline (Log Dmin) was significantly lower than that in N-group (0.47 +/- 0.60 log units vs. 0.98 +/- 0.60 log units respectively, p < 0.05). Log Dmin was significantly correlated with the dose of acetylcholine which induced a greater than 90% stenosis of the coronary artery (r = 0.383, p < 0.05). We concluded that both the coronary artery and the airway show hyperresponsiveness to cholinergic agonists in patients with VSAP.

Aged↗

[Radiotherapy for adenocarcinoma of the uterine cervix].

One hundred three patients with adenocarcinoma of the uterine cervix treated with radiotherapy between 1975 and 1992 were evaluated. The results for 24 patients treated with radiotherapy alone were as follows: The overall 5-year survival rates for Stages I + II (N = 12) and III + IV (N = 12) were 52% and 16%, respectively, lower than those for squamous cell carcinoma (stage I: 89%, II: 54%, III: 44%, IV: 19%). The overall response rate was 79.1%, and the recurrence rate was 54.2% (local recurrence: 29.2%, distant metastasis: 33.3%). In Stage I + II patients with an intracavitary irradiation dose of 40 Gy (LDR) or more, there was no local recurrence. In stage III + IV patients, local recurrence was recognized in spite of the high dosage of intracavitary irradiation. The results for 79 patients treated with combined irradiation and operation were as follows: The overall 5-year survival rates for Stages I, II, III and IV were 76%, 60%, 57%, and 0%, respectively. The incidence of lymph node metastasis was 30.4%, and for Stages I, II, III and IV was 26.7%, 34.6%, 28.6%, and 100%, respectively. This showed that adenocarcinoma had a higher incidence of lymph node metastasis after the early stage. The recurrence rate for patients with lymph node metastasis was 75.0%, significantly higher than 25.4% for patients without lymph node metastasis (p < 0.001). To improve prognosis, 40 Gy or more of intracavitary irradiation dose (LDR) and systemic chemotherapy to prevent distant metastasis are recommended for stage I and II cases. For stage III and IV cases, it was thought to be difficult to control local disease with radiation alone. Additional treatment should be used for these cases, i.e. intraarterial infusion, chemotherapy, hyperthermia and so on.

Adenocarcinoma↗

Molecular cloning and characterization of the gene encoding 53 kD outer membrane protein of Porphyromonas gingivalis.

The pga53 gene which encoded the antigenic 53 kD outer membrane protein (Ag53) was isolated from a genomic DNA library of Porphyromonas gingivalis FDC381 by using an Ag53-immunized rabbit serum. Determination of its complete nucleotide sequence revealed that the precursor of Ag53 had a 50 amino-acid putative signal sequence and the mature protein of 448 amino acids. The deduced amino acid sequence after a 50 amino-acid putative signal sequence was in complete agreement with the first 20 N-terminal amino acids of purified Ag53. Analysis of the deduced amino acid sequence revealed the presence of a highly hydrophilic proline-rich region at the C-terminal of Ag53. The deduced amino acid sequence showed 29.9% homology with that of a 72 kD cell-surface protein in P. gingivalis. Southern hybridization revealed that pga53 was specific to several P. gingivalis strains and that P. gingivalis strains which did not possess Ag53 had genes homologous to pga53.

Amino Acid Sequence↗

Increased portal endothelin-1 level is associated with the liver function after cardiopulmonary bypass in rabbits: influence of hypothermia on the damage.

The purpose of this study was to prove the hypothesis that ET-1 production is increased in the splanchnic-hepato circulation during cardiopulmonary bypass (CPB) with or without hypothermia and this greatly affects hepatocellular function after surgery. Twelve Japanese white rabbits were used. In group I (n = 6), the rectal temperature was kept at 37.0 degrees C during CPB (90 min). In group II (n = 6), the rectal temperature was lowered to 26 degrees C during the first 30 minutes and then increased to 37 degrees C for the following 60 minutes. In group I, surface liver tissue blood flow (LBF) remained stable during CPB. While, in group II, LBF was significantly reduced to 66.9% of baseline values during hypothermic CPB, but it increased during the rewarming phase to 84.3% of the baseline value (p = 0.0070). At the end of CPB, portal ET-1 levels were increased in both groups, but they were significantly higher in group II (7.32 +/- 0.50 pg/ml and 9.29 +/- 0.61 pg/ml, respectively). Serum GOT, GPT, LDH and arterial ammonia levels were also higher in group II. Portal ET-1 levels had a significant positive correlation with those liver enzymes. Histopathological examination after CPB showed severe damage of the hepatic parenchyma in zone 3 associated with microvesicular fatty infiltration in group II.

Analysis of Variance↗

Estimation of carboxyhemoglobin concentrations in thermo-coagulated blood on a CO-oximeter system: an experimental study.

In order for forensic toxicological application of a CO-oximeter system to carboxyhemoglobin (CO-Hb) analysis of thermo-coagulated blood, an experimental study was performed. Blood samples containing varying concentrations of CO-Hb were gradually heated up to 70-80 degrees C in ca. 1-13 min, and the extracts (soluble fractions) were examined. CO-Hb contents in the extracts did not represent those in whole thermo-coagulated blood, showing a considerable increase especially for the samples with the initial CO-Hb levels of ca. 25-50%. Changes in CO-Hb % measurements depended little on the heating time but greatly on the final temperature of the blood. The apparent increase in CO-Hb measurements proved to be significantly related to the decrease in total soluble hemoglobin due to thermo-coagulation which depended on the CO-Hb contents, not due to CO-Hb formation by heat. Although gas chromatographic analysis of CO combined with appropriate measurement of total hemoglobin would be required for accurate CO-Hb determination of thermo-coagulated blood, a possible method for rough estimation (semiquantitative screening) of CO-Hb content in whole thermo-coagulated blood with the CO-oximeter was proposed on the basis of thermostability of CO-Hb. The estimated CO-Hb values correlated with the contents measured by a gas chromatographic method independently of the heating time or final temperature up to 80 degrees C.

Adult↗

Immunohistochemical investigation of pulmonary surfactant in perinatal fatalities.

In order to verify forensic pathological significance of immunohistochemical investigation of pulmonary surfactant, 11 forensic and 16 clinico-pathological cases of perinatal death were comparatively examined. Surfactant appeared in some infants of 31-32 weeks gestation and was usually positive thereafter, indicating maturity of fetal lungs, although it may not have fully developed until about the 36th week of gestation. It was negative in all cases of the hyaline membrane disease except for a full-term infant (secondary respiratory distress syndrome). In usual cases, surfactant coating the expanded alveolar epithelia with its diffuse deposit in the intra-alveolar spaces was considered to indicate duration of hypoxia under persistent respiration (agonal state). Such finding was most intensely observed in asphyxia and in severe respiratory failure from intrinsic causes in the infants over ca. 36 weeks of gestation. With reference to pulmonary micromorphology, the amount of intra-alveolar surfactant seemed to be most closely related to the alveolar septal (interstitial) edema.

Cause of Death↗

Isolation and analysis of a novel gene, HXC-26, adjacent to the rab GDP dissociation inhibitor gene located at human chromosome Xq28 region.

We screened potential promoter regions from NotI-linking cosmid clones mapped on human chromosome Xq28 region with our constructed trapping vector and isolated six fragments containing transcription activity. Using one of the obtained fragments as a probe, a novel gene was isolated by screening a human skeletal muscle cDNA library. The isolated cDNA, termed HXC-26, contained an open reading frame of 975 nucleotides encoding 325 amino acids (38,848 Da). The HXC-26 gene was composed of 13 exons that span approximately 8 kb. Several potential GC boxes were found in the putative promoter region, but no typical TATA box. The HXC-26 gene associated with a CpG island was located adjacent to the rab GDP dissociation inhibitor (GDI) gene.

Amino Acid Sequence↗

Constructing an efficient trans-acting genomic HDV ribozyme.

We have engineered a genomic HDV ribozyme to construct several trans-acting ribozymes for use in trans to cleave target RNAs. Among the 10 different combinations attempted, only HDV88-Trans had cleavage activity on the 13-nucleotide substrate, R13, in vitro. To improve the cleavage efficiency, at least in vitro, of the HDV88-Trans ribozyme (kclv = 0.022 min(-1)), we have constructed several variants that differ in forming stem II (length) in the pseudoknot secondary structure model. When cleavage rate constants were analyzed and compared among variants of HDV88-Trans, HDV88-Trans-4 yielded kclv = 1.7 min(-1). HDV88-Trans-4 thus represents the highest active genomic HDV ribozyme that functions in trans thus far constructed, and has activity under physiological conditions (pH 7.1 at 37 degrees C with 1 mM of MgCl2).

Base Sequence↗

Evaluation of post-mortem oxymetry in fire victims.

In order to investigate the pathophysiology of death due to fires, we examined blood samples of 48 fire victims on CO-oximeter systems and evaluated the oxymetric differences between arterial and venous blood as well as those between the heart and peripheral blood. Post-mortem carboxyhemoglobin (CO-Hb) levels in the left and right heart blood, respectively, ranged from 1.2 to 94.7% and from 0.4 to 90.5%. Marked arterio-venous and centro-peripheral differences were observed in the cases of high CO-Hb (above ca. 70%), suggesting an immediate effect of fatal carbon monoxide (CO) poisoning probably accompanied with acute heart failure. A relatively high oxyhemoglobin level was observed in the cases of low CO-Hb (below ca. 30%). In some cases, reduced hemoglobin levels in the left heart blood were paradoxically somewhat higher than those in the right. These oxymetric profiles may assist to consider the final balance of blood gas in fire victims depending on increased CO, carbon dioxide, and reduction of oxygen in the ambient atmosphere due to combustion, although post-mortem interference should be taken into consideration.

Adolescent↗

Cloning of a human homolog of the Drosophila minibrain/rat Dyrk gene from "the Down syndrome critical region" of chromosome 21.

To isolate genes responsible for some features of Down syndrome, we performed exon trapping experiments using a series of cosmid clones derived from "the Down syndrome critical region" of chromosome 21 and isolated six exons which are highly homologous to the sequence of Drosophila minibrain (mnb) gene. The Drosophila mnb gene encodes a serine/threonine protein kinase that is required in distinct neuroblast proliferation centers during postembryonic neurogenesis. Using one of these six exons as a probe, we isolated cDNA clones for human homolog of Drosophila mnb gene (MNB) from a fetal brain cDNA library. Human MNB cDNA encodes a protein of 754 amino acids with a nuclear targeting sequence and a catalytic domain common to the serine/threonine-specific protein kinase. The human MNB protein strikingly resembles the recently discovered rat Dyrk protein kinase with a dual specificity. The MNB mRNA is expressed in various tissues including fetal and adult brains. The remarkable similarity of human MNB protein to Drosophila mnb and rat Dyrk proteins implies that human MNB protein may play a significant role in a signaling pathway regulating nuclear functions of neuronal cell proliferation, contributing to certain features of Down syndrome.

Adult↗

The mammalian single-minded (SIM) gene: mouse cDNA structure and diencephalic expression indicate a candidate gene for Down syndrome.

We have recently isolated a human homolog (hSIM) of the Drosophila single-minded (sim) gene from the Down syndrome critical region of chromosome 21 using the exon trapping method. The Drosophila sim gene encodes a transcription factor that regulates the development of the central nervous system midline cell lineage. To elucidate the structure of the mammalian SIM protein, we have isolated cDNA clones from a mouse embryo cDNA library. The cDNA clones encode a polypeptide of 657 amino acids with a bHLH (basic-helix-loop-helix) domain, characteristic of a large family of transcription factors, and a PAS (Per-Arnt-Sim) domain in the amino-terminal half region. Both of these domains have striking sequence homology with human SIM and Drosophila SIM proteins. In contrast, the carboxy-terminal half of the mouse SIM protein consists of a proline-rich region with no sequence homology to the Drosophila SIM protein. A similar proline-rich domain is known for the activator domain of a number of transcription factors. Whole-mount embryo in situ hybridization experiments revealed that the SIM mRNA is expressed prominently in the diencephalon of mouse embryos at 8-9.5 days postcoitum. The structural characteristics of the mouse SIM protein and its expression in the diencephalon during embryogenesis strongly suggest that the newly isolated mammalian SIM homolog may play a critical role in the development of the mammalian central nervous system. We propose that the human SIM gene may be one of the pathogenic genes of Down syndrome.

Animals↗

Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth.

BACKGROUND: Rapid tumor growth is caused by angiogenesis factors, growth factors, etc. We previously reported a possible connection between nitric oxide (NO) and enhanced vascular permeability in solid tumor. In the present experiment, the role of NO in solid tumor pathology was further investigated in animal tumor. METHODS: To identify NO formed in solid tumor (AH136B) implanted in the feet of rats, electron paramagnetic resonance (EPR) spectroscopy was performed directly on the frozen tumor tissue at 110K by measuring endogenous nitrosyl iron-sulfur complexes, and by using exogenously added NO capturing agents, i.e., diethyldithiocarbamate (DETC)-Fe2+ and N-(dithiocarboxy) sarcosine (DTCS)-Fe2+ complexes. Induction of inducible isoform of nosymthase iNOS mRNA was examined with reverse transcriptase-polymerase chain reaction (RT-PCR) combined with Southern blot analysis. In addition, vascular permeability was assessed by measuring extravasation of 51Cr-labeled bovine serum albumin in solid tumor. RESULTS: Strong EPR signals from NO adducts of DETC-Fe2+ and DTCS-Fe2+ as well as strong signals from NO-hemoglobin and dinitrosyl iron sulfur complex were generated by tumor. The signal height of NO-(DTCS)2-Fe2+ observed in AH136B solid tumor was increased as the tumor gained up to 1.75 g. Induction of iNOS mRNA expression was confirmed by the above methods. Enhanced vascular permeability was suppressed by NOS inhibitors N omega- monomethyl-L-arginine or S-methylisothiourea sulfate and augmented with administration of L-arginine. CONCLUSIONS: Excessive NO production by iNOS in solid tumor was identified unequivocally by EPR spectroscopy. NO formed in solid tumor can be involved in enhanced vascular permeability and increased blood flow, and hence sustain tumor growth.

Animals↗

Changes in cellular components of spleen and lymph node cells and the effector cells responsible for Meth A tumor eradication induced by zinostatin stimalamer.

We reported previously that pretreatment with zinostatin stimalamer (ZSS) eradicated Meth A tumors in BALB/c mice. We herein investigated cellular components of spleen and lymph node cells of Meth A-bearing ZSS-pretreated mice by flow cytometry; the antitumor effector cells by in vivo depletion of T cells, NK cells, or macrophages; and host-mediated antitumor activity associated with ZSS treatment after tumor transplantation. ZSS given on day-3 transiently decreased the number of spleen cells. The percentage of T cells increased, but B cells and macrophages decreased. B cells decreased in inguinal lymph nodes in Meth A-bearing ZSS-pretreated mice, but increased in Meth A-bearing control mice. In vivo depletion experiments using antibodies or carrageenan showed that antitumor effector cells for tumor eradication are Thy1.2+/Lyt2.2+ and that at least a part of them are asialo GM1+. Thy1.2+/Lyt2.2+/asialoGM1- cells are important in generation of the antitumor activity of ZSS; however, L3T4+ T cells are also involved in initiation of tumor eradication. The result of ZSS treatment after tumor transplantation suggests that ZSS might exhibit antitumor activity by augementating host-mediated antitumor resistance, as well as its intrinsic cytocidal activity.

Animals↗

Syntheses of 1-O-carboxyalkyl GLA-60 analogues.

As part of our ongoing study to survey potent LPS antagonists, the following six compounds were synthesized in an efficient manner: 3-carboxypropyl and carboxymethyl 2-deoxy-2-(2,2-difluorotetradecanamido)-4-O-phosphono-3-O-[(R)-3- (tetradecanoyloxy)tetradecanoyl]-alpha- and beta-D-glucopyranosides (11 and 23; 32 and 36), as well as the non-fluorinated equivalents, carboxymethyl 2-deoxy-4-O-phosphono-2-tetradecanamido-3-O-[(R)-3-(tetradecano yloxy)- tetradecanoyl]-alpha-D-glucopyranoside (44) and carboxymethyl 2-deoxy-2-[(R)-3-(hydroxy)tetradecanamido]-4-O-phosphono-3-O-[(R)- 3- (tetradecanoyloxy)tetradecanoyl]-alpha-D-glucopyranoside (48). Of these compounds, 32 was most pronounced in terms of LPS-antagonistic activity.

Carbohydrate Conformation↗