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Biomedical subjects

H Maeda

Publications and source records attributed to H Maeda.

At least 649 records · Page 36Linked to original sources

Specificity for various imino-acid-residues of a proline-specific dipeptidylcarboxypeptidase from a Streptomyces species.

A proline-specific dipeptidylcarboxypeptidase, which removes diproline from the C-terminus of the proline-containing peptides, such as Boc-Pro-Pro-Pro-Pro and Leu-Pro-Pro-Pro-Pro-Pro, has recently been purified from a Streptomyces sp. The specificity of the enzyme for various imino acid-containing synthetic peptide substrates was further studied. The peptides with proline, hydroxyproline, or dehydroproline at the P2' position were found to be good substrates, while those with pipecolic acid, D-proline or other usual amino acids at the P2' position were scarcely hydrolyzed. The peptides with proline, dehydroproline, pipecolic acid, or N-methyl-alanine at the P1' position were well-hydrolyzed, while those with hydroxyproline or D-proline at the P1' position were not hydrolyzed. Utilizing this high specificity for imino acids, Boc-Pro-Pro-Pro-Pro was synthesized by the enzyme using Boc-Pro-Pro as the acidic component and Pro-Pro as the basic component.

Amino Acid Sequence↗

Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction.

A labile inorganic free radical, nitric oxide (.NO), is produced by nitric oxide synthase from the substrate L-arginine in various cells and tissues. It acts as an endothelium-derived relaxing factor (EDRF) or as a neurotransmitter in vivo. We investigated the reactivity of stable radical compounds, imidazolineoxyl N-oxides such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), carboxy-PTIO, and carboxymethoxy-PTIO against .NO/EDRF in both chemical and biological systems. By using electron spin resonance (ESR) spectroscopy, imidazolineoxyl N-oxides were found to react with .NO in a stoichiometric manner (PTIO/.NO = 1.0) in a neutral solution (sodium phosphate buffer, pH 7.4) with rate constants of approximately 10(4) M-1 s-1, resulting in the generation of NO2-/NO3- and imidazolineoxyls such as 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl (PTI), carboxy-PTI, or carboxymethoxy-PTI. Furthermore, the effects of imidazolineoxyl N-oxides on acetylcholine- or ATP-induced relaxation of the smooth muscle of rabbit aorta were tested. The vasorelaxations were inhibited by all three imidazolineoxyl N-oxides markedly. The inhibitory effects of carboxy-PTIO was almost 2-fold stronger than those of .NO synthesis inhibitors, N omega-nitro-L-arginine and N omega-monomethyl-L-arginine. Generation of EDRF/.NO was identified by reacting the PTIO in aortic strips and quantitating the reaction product with ESR spectroscopy. Thus, it was clarified that imidazolineoxyl N-oxide antagonize EDRF/.NO via a unique radical-radical reaction with .NO.

Acetylcholine↗

A wireless axial pair resonator.

A wireless axial pair resonator consists of two coils coupling inductively with a body coil, which is used as a signal transmitter and receiver. Computer simulations gave signal enhancements of 1.41 and 1.47 for the resonators of 15- and 20-cm diameter, whereas those of phantom studies gave 1.37 and 1.49.

Computer Simulation↗

Absence of bcr/abl gene in single hemopoietic progenitors in some patients with chronic myelogenous leukemia.

CD34+DR- and CD34+DR+ cells were isolated from the marrow mononuclear cells of five patients with chronic myelogenous leukemia (CML) carrying the Philadelphia (Ph) chromosome. Analysis of bcr/abl hybrid mRNA in individual colonies from a single cell using reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated the presence or absence of the hybrid mRNA. For patient 1 in the chronic phase of CML, the hybrid mRNA was detected in all colonies derived from CD34+DR+ and CD34+DR- hemopoietic progenitors. In contrast, for patient 2 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ progenitors but not in any from CD34+DR- progenitors. For patient 3 in the chronic phase of CML, the mRNA was detected in all individual colonies from CD34+DR+ but in only some of the colonies from CD34+DR- progenitors. For patients 4 and 5 in the acute crisis of CML, the mRNA was found in a portion of colonies from CD34+DR+ and CD34+DR- progenitors. These results indicated that normal clones can persist in CD34+DR- progenitors in some patients with CML, even when chromosome analysis detects the Ph chromosome in all metaphases of bone marrow cells.

Adult↗

Modulation of glutathione S-transferase activity by a thiol/disulfide exchange reaction and involvement of thioltransferase.

Low concentrations of cystamine and cystine inactivated human placenta glutathione S-transferase (GST-pi) in cytosolic fraction very effectively, as did the purified enzyme, through the thiol/disulfide exchange reaction. Mixed disulfide formation of GST-pi in cytosol was prevented by thioltransferase existing in cytosol with a low concentration of GSH. This protection of GST-pi activity was more effective with the participation of glutathione reductase. The incorporation of half-[14C]cystine into a GST-pi molecule according to the inactivation was provided by autoradiography. Purified human placenta thioltransferase (1900-fold from cytosol) could release the incorporated half-[14C]cystine from a GST-pi molecule with restoration of enzyme activity. Thioredoxin in placenta cytosol could not protect the GST-pi activity from inactivation at all.

Chromatography, Affinity↗

Role of bradykinin in microbial infection: enhancement of septicemia by microbial proteases and kinin.

Data presented herein will show that bradykinin, microbial proteases which activate the kinin generating cascade, and kininase inhibitors can enhance septicemia by approximately 10 to 100 fold in mice infected intraperitoneally (i.p.) with a strain of bacteria, Pseudomonas aeruginosa 621, which does not usually produce a kinin generating protease. Bacterial spreading was evaluated either in the blood or in the spleen by colony formation on agar plates. Using the P. aeruginosa kaguma strain which produces a large amount of proteases, further experiments were carried out. Results showed that two different protease inhibitors (ovomacroglobulin and a synthetic peptide inhibitor against pseudomonal elastase) as well as a kinin antagonist suppressed bacterial dissemination to 1/10-1/100 of control. Similar results were observed in experiments using Vibrio vulnificus. These data support the hypothesis that microbial proteases and especially bradykinin is responsible for facilitation of microbial dissemination in vivo.

Animals↗

Chromosome abnormalities in peripheral lymphocytes from patients with progressive systemic sclerosis.

Chromosomal abnormalities in cultured peripheral lymphocytes from 14 progressive systemic sclerosis (PSS) patients and 15 normal subjects were examined. No increase was observed in the frequency of chromosome aberrations in PSS patients who had not received any medical treatment. Those who had received medication showed an increased frequency of dicentrics (0.3%) although the frequency was not significantly higher than that for normal subjects. It is not clear, however, whether the increase was due to the hypersensitivity of PSS patients to agents used for therapeutic purposes.

Adult↗

Severe respiratory depression after epidural morphine in a patient with myotonic dystrophy.

We describe a patient with myotonic dystrophy who underwent cholecystectomy, and developed severe respiratory depression following epidural administration of morphine to provide postoperative analgesia. At preoperative assessment, he demonstrated near normal vital capacity and maximal voluntary ventilation, but the presence of chronic ventilatory failure with a resting value of PaCO2 51 mmHg. Anaesthesia was produced by a combination of epidural and light general anaesthesia without intravenous anaesthetics, narcotics or neuromuscular relaxants. Five hours after epidural administration of 2 mg morphine, the patient developed severe respiratory depression with a PaCO2 of 93 mmHg. Intravenous naloxone resulted in transient improvement in minute volume, suggesting that epidural morphine was responsible for the depression. Epidural morphine can cause unexpected respiratory depression, even at a small dose, because of the sensitivity of the respiratory centre to morphine in patients with myotonic dystrophy.

Analgesia, Epidural↗

Retardation of mouse odontoblast differentiation by heparin in vitro.

The effect of heparin was studied histologically and immunohistochemically. Tooth germs from 15-day-old mouse embryos were cultured with or without heparin. After 6 days of culture in control medium, mesenchymal cells underlying the inner enamel epithelium had differentiated into odontoblasts and secreted predentine. In medium with heparin, mesenchymal cells were undifferentiated. In medium with other glycosaminoglycans such as chondroitin sulphate, dermatan sulphate or hyaluronate, tooth germs were similar to those in control medium, as were those in medium with heparin-Sepharose absorbed serum. After 12 days of culture in the heparin medium, mesenchymal cells in some cusps had differentiated into odontoblasts and secreted predentine but in other cusps remained undifferentiated. Immunohistochemically, exogenous heparin did not prevent the deposition of type IV collagen, laminin and fibronectin in the basement membrane and extracellular matrix. These results suggest that exogenous heparin retards differentiation of odontoblasts but not by disruption of the basement membrane nor inactivation of heparin-binding growth factors present in serum.

Animals↗

Magnetic resonance images of hematospermia.

Seminal vesicles and their adjacent structures were studied using magnetic resonance imaging (MRI) in 7 normal volunteers and 15 patients with hematospermia. Normal seminal vesicles are depicted on T2-weighted images either as a mixture of high- and low-signal granules or as a convolution of tubules with a diameter of less than 0.5 cm. Fourteen of the 15 patients with hematospermia exhibited abnormalities on MRI. Dilatation or cyst formation in the seminal vesicle was observed in 13 patients, and a dilatation of the midline structure was seen in 3 patients. Abnormal signal intensity of the seminal vesicles was seen in 11 patients and was thought to be due to subacute hemorrhage.

Adult↗

Immunomodulating activities of orally administered SMANCS, a polymer-conjugated derivative of the proteinaceous antibiotic neocarzinostatin, in an oily formulation.

Immunomodulatory effects of oily formulated SMANCS, a polymer conjugated derivative of the proteinaceous antibiotic neocarzinostatin, after oral administrations to mice was investigated. The oral administrations of SMANCS, dissolved in medium-chain triglyceride containing phosphatidylcholine and polyglycerine dioleate (oily SMANCS), resulted in: (1) augmentation of NK cell activity in naive mice, (2) activation of macrophage cytostasis in naive mice, (3) enhancement of the generation of cytotoxic T-lymphocytes in mice immunized with allogeneic lymphocytes, (4) production of circulating interferon in naive mice, and (5) increase of delayed-type hypersensitivity response in mice immunized with sheep red blood cells. The degree of immunomodulation orally stimulated with oily SMANCS was similar to that of the immunomodulation induced by i.v. or i.p. administrations of aqueous formulated SMANCS (aqueous SMANCS). Although SMANCS is a protein drug that may be digestable by various enzymes present in the stomach, in the present study immunomodulating activities of SMANCS were clearly demonstrated when an oily formulation of the compound was administered to mice orally. Since aqueous SMANCS administered parenterally and oily SMANCS administered orally exhibit the same immunomodulatory activities and the former has demonstrated antitumor activity in man and animals, the latter may possess this same antitumor activity.

Adjuvants, Immunologic↗

Cutaneous papillomatosis associated with papillomavirus infection in a dog.

A 7-year-old female Kerry blue terrier dog developed 20 cutaneous nodules, up to 4 mm in diameter, over the body. Light and electron microscopy demonstrated that they were virus-associated inverted papillomas and they are described because canine skin viral papillomas have not been frequently reported.

Animals↗

Augmentation of tumour delivery of macromolecular drugs with reduced bone marrow delivery by elevating blood pressure.

Effects of angiotensin II (AT-II)-induced hypertension on the distribution of macromolecules to Walker carcinoma and to bone marrow of SMANCS [poly(styrene-co-maleic-acid)-neocarzinostatin conjugate] were investigated in rats. AT-II-induced hypertension from about 100 to 150 mmHg significantly increased the accumulation of the macromolecular drug SMANCS and 51Cr-labelled bovine serum albumin ([51Cr]BSA), representatives of macromolecular drugs, in tumour tissue. At 1 h after i.v. administration, intratumour concentrations of [51Cr]BSA and SMANCS were elevated by 1.2-1.8-fold. The higher drug accumulation in the tumour that was produced by the artificial hypertension was retained even 6 h after administration. This observation indicates an additive effect to that under normotensive conditions where intratumour macromolecular drug concentrations increase steadily during this period. Furthermore, distributions of these drugs in the bone marrow and the small intestine decreased during artificial hypertension to 60-80% of those in the normotensive state. Therefore, the drug concentration ratios of tumour/bone marrow and tumour/small intestine were increased by 1.8-2.4-fold. A decreased distribution of SMANCS to normal tissues under hypertensive conditions was also confirmed by the significant reduction of its toxicity e.g. leukopenia, diarrhoea, and body weight loss, even at a lethal dose. On the contrary, [3H]methylglucose showed no remarkable difference in tumour or bone marrow accumulation under this hypertensive condition. These results show the advantages of macromolecules over small molecules for AT-II-induced hypertension chemotherapy.

Angiotensin II↗

The suppressive effect of gelatin-conjugated superoxide dismutase on disease development and severity of collagen-induced arthritis in mice.

We studied the effect of superoxide dismutase (SOD) on murine collagen-induced arthritis (CIA), an animal model of human rheumatoid arthritis (RA). Among SOD derivatives studied, only gelatin-SOD conjugate which has prolonged half life in vivo was effective to suppress the development of CIA, while native SOD or gelatin carrier alone was ineffective. Interestingly, pyran polymer-conjugated SOD which also has a long half life showed no suppressive effect on the disease. No significant effect on immune response against type II collagen (CII) was found in any of the experimental groups. In addition, induction of suppressor cells was not detected in spleen or lymph node cells of the gelatin-SOD-treated group. Therefore, these results suggest that oxygen radicals may have an important role in the effector phase of the immune response to manifest this chronic autoimmune polyarthritis. Thus, the use of appropriate antioxidants for the treatment of human RA may be rationalized.

Animals↗

Unique associations between HLA-B and HLA-DRB1*04 gene variants in Japanese.

HLA-DRB1*04 gene variants were determined in apparently healthy Japanese with PCR-SSCP and PCR-RFLP, and HLA-B-DRB1*04 haplotype frequencies were estimated statistically. DRB1*0405, which consisted of 60% of the Japanese DRB1*04 gene pool, was associated strongly with HLA-B54. This association was observed only for DRB1*0405, and not for any other DR4 variants. DRB1*0403 and DRB1*0406, which share the same peptide sequence except for amino acid 37, were both associated with B35 and B62. DRB1*0407 was associated exclusively with B35. DRB1*0410 was associated with B60 and B61. B60 and B61, on the other hand, were associated only with DRB1*0410 and DRB1*0405. B35 was associated with all DR4 microvariants. With this possible exception, our calculation suggests that unique B-DR associations were present even for DR4 microvariants. The knowledge of HLA-B and DRB1*04 associations would be useful in clinical settings.

Asian People↗

Hodgkin's-like lymphoma in a dog.

This is the first reported case of canine Hodgkin's-like lymphoma in Japan. Tumor growth involved the lymph nodes and multiple visceral organs. Histopathological examination revealed that the tumor consisted of a large number of typical Reed-Sternberg cells with symmetrically arranged nuclei, the so-called "mirror-image" cells, intermingled with various numbers of inflammatory cells and globule leucocytes.

Animals↗