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Biomedical subjects

H Akagi

Publications and source records attributed to H Akagi.

At least 19 recordsLinked to original sources
PubMed1992

Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels.

Functional maturation of the nicotinic acetylcholine receptor is executed by its gamma-to-epsilon subunit switching. The glycine receptor also has fetal (alpha 2) and adult (alpha 1) isoforms. However, whether subunit switching is responsible for developmental changes in glycine receptor function is not known. We recorded single-channel currents from homomeric glycine receptors expressed in Xenopus oocytes with cRNAs encoding the alpha 2 or alpha 1 subunits and compared them with those recorded from native glycine receptors in rat spinal neurons at various ontogenic periods. The mean channel life times of the alpha 1 and mature glycine receptors were equally short, whereas both the alpha 2 and fetal receptors showed a significantly longer open time. Consistent with these results, the decay time of the glycinergic inhibitory postsynaptic currents (IPSCs) in spinal neurons became shorter during postnatal development. We conclude that developmental switching of alpha subunits may accelerate the kinetics of IPSCs.

Aging↗
PubMed1992

Patients with homocystinuria: high metal concentrations in hair, blood and urine.

Patients with homocystinuria excrete a large amount of metal in their urine. Homocysteine similar to penicillamine, administration to methylmercury treated rats resulted in a large amount of urinary methylmercury excretion. These results suggested that the total metal amounts in the whole body of patients with homocystinuria might be decreased. However, actually metal concentrations in hair and plasma of these patients were higher than those of normal controls. High plasma and hair metal levels are not accounted for in patients with homocystinuria. The physiological metal excretory mechanism in which small amounts of metals bind to the small, plasma molecular substances filter through the kidney and emerge in the urine is necessary for reconfirmation. Strongly perturbed metal metabolism exists in the patients with homocystinuria.

Adult↗
PubMed1992

[Expression and function of glycine-gated Cl- channels].

Glycine is a major inhibitory neurotransmitter in the spinal cord and brain stem. Glycine acts by increasing the Cl- permeability through activation of a specific receptor/ion channel complex consisting of a pentameric subunit assembly. Molecular cloning has disclosed the nature of receptor subunits alpha and beta. While the role of the beta subunit is still unclear, the alpha subunit functions in both ligand (agonist/antagonist) binding and ion channel formation. It has been demonstrated that there are two isoforms of the alpha subunit, alpha 1 and alpha 2. The mRNAs encoding these subunit isomers are transcribed from different genes, in spite of their structural similarity. The alpha 1 mRNA is abundant in adult spinal cord, whereas the alpha 2 mRNA is mainly expressed in developing spinal cord as well as various regions of brain tissue. The single channel properties were examined in outside-out patches excised from Xenopus oocyte membrane expressing alpha 1 or alpha 2 homomeric receptors. The mean open time of alpha 2 channels was 70-times longer than that of alpha 1 channels. The subunit switching from alpha 2 to alpha 1, and resulting shortening of channel kinetics, may ensure a rapid motor control in adult animals.

Animals↗
PubMed1991

Cloning of a glycine receptor subtype expressed in rat brain and spinal cord during a specific period of neuronal development.

Complementary (c) DNAs encoding a glycine receptor (GlyR) isomer were cloned from libraries constructed in lambda ZAPII with poly (A)+ RNA of neonatal rat spinal cord. Northern blot analysis revealed that RNA hybridized to the cloned cDNA is detectable only for a period of late embryonic/early postnatal stage of the spinal cord. Moreover, other central nervous tissues, such as hippocampus and cerebral cortex, in the infant rats are also rich in this message. The 'neonatal (N) GlyR' has 71% homology to that of another GlyR isoform in which adult rad cord is rich (AGlyR). Injection of a single RNA transcribed from the NGlyr-cDNA into Xenopus oocyte induced functional formation of glycine-gated Cl- channels, however, its pharmacological property differed from that of AGlyR.

Amino Acid Sequence↗
PubMed1991

Functional properties of strychnine-sensitive glycine receptors expressed in Xenopus oocytes injected with a single mRNA.

Mature rat spinal cord cDNA libraries constructed in lambda gt10 and lambda ZAPII were screened with an oligonucleotide probe (39 mer), and 4 clones that possess DNA-inserts encoding a glycine receptor subunit were obtained. The cloned cDNAs were used to reconstruct the nucleotide sequence of the full-length open reading frame consisting of 1350 base pairs (bp) as well as the 5'-(184 bp) and 3'-(591 bp) non-coding regions. Synthetic RNA transcribed in vitro from the glycine receptor cDNA induced Xenopus oocytes to synthesize functional glycine receptor that generated large Cl- currents. The electrophysiological properties of the wild-type receptor and some mutant receptors produced by site-directed mutagenesis were analyzed.

Acetylcholine↗
PubMed1991

Long-term respiratory assistance using a right ventricular assist device system and a membrane oxygenator.

A new method for long-term respiratory assistance using a right ventricular assist device (RVAD) system and a membrane oxygenator (MO) was designed and evaluated. An air-driven RVAD was implanted between the right atrium and the pulmonary artery in five goats and an MO was set on the outlet conduit of the RVAD 2 weeks postoperatively. Two types of MOs [the SciMed (Life Systems) silicone sheet MO and a prototype MO using a novel multilayered composite membrane] were used in this study. Respiratory support with this system under systemic heparinization could be conducted for 4-8 days without major problems accompanied with conventional extracorporeal membrane oxygenation (ECMO) such as surgical bleeding, destruction of the blood components, serum leakage, insufficient bypass flow, and fatal systemic thrombosis. This method opened the possibility for ECMO to be used as a bridge before lung or heart-lung transplantation.

Animals↗
PubMed1991

Presence of human papillomavirus genome in human tumor cell lines and cultured cells.

A series of 47 human carcinoma cell lines and their cultured cells were examined for human papillomavirus (HPV) genomes with the use of an HPV detection kit (DNA-RNA hybridization, mixed HPV DNA probe of types 6, 11, 16, 18, 31, 33 and 35). Four of 8 cases of mild dysplasia, 3 of 9 cases of severe dysplasia, 3 of 7 cases of carcinoma in situ, 3 of 15 cases of uterine carcinoma and 5 of 6 cases of condyloma acuminatum were shown to contain the HPV DNA genome in primary cultured cells, while HPV was not detected in the third-passage cells except for the three cases of large cell, nonkeratinizing squamous cell carcinoma. HPV was also not detected in such normal tissues as uterine cervical squamous epithelium, uterine cervical columnar epithelium and endometrium. The presence of HPV DNA genomes was detected consistently in the passages of three lines (SKG-II, HKMUS and HKTUS; large cell nonkeratinizing squamous cell carcinomas of the uterine cervix) with the use of the Southern Blot method (DNA-DNA hybridization, mixed HPV probe of types 6, 11, 16 and 18). HPV type 16 DNA was detected in HKTUS, and HPV type 18 DNA was found in SKG-II and HKMUS. The other 44 cell lines, including ovarian carcinoma, endometrial carcinoma, sarcoma, gastric cancer, pancreatic cancer and rectal cancer, were negative for the HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33 and HPV-35 genomes under stringent hybridization conditions.

Adenocarcinoma↗
PubMed1991

[The artificial heart: present status and future prospects].

Artificial heart (AH) and heart transplantation (HTx) are complementary means of cardiac assistance and replacement. Temporary use AH including ventricular assist systems (VASs) and total artificial hearts (TAHs) have been put into clinical use. VASs applied to 848 patients in the world and 187 in Japan with acute profound heart failure. The short-term survival rates are 23.3% and 27.3%, respectively. HTx has become an accepted therapeutic procedures. To date, 255 patients received VAS and 182 received TAH as a bridge to HTx, because the number of candidates exceeds the supply of donor hearts. Long-term implantable AH is the future alternatives for cardiac replacement. It is recognized that several key components will be necessary for development of an AH with high performance including biomaterial with antithrombogenecity and durability, an implantable actuator, a noninvasive monitoring system and sensors, a miniature auto-control system, and an energy converter. Another types of devices are on the horizon. These are a muscle-powered biomechanical AH, an AH powered by artificial muscle, and an integrated artificial heart-lung device. With remarkable progress in medicine and engineering, we can expect to see totally implantable permanent use cardiac assist and replacement devices as an alternative for HTx in the near future.

Heart, Artificial↗
PubMed1990

A potent metabotropic glutamate receptor agonist: electrophysiological actions of a conformationally restricted glutamate analogue in the rat spinal cord and Xenopus oocytes.

The (2S,3S,4S) isomer of alpha-(carboxycyclopropyl)glycine (L-CCG-I), a conformationally restricted glutamate analogue, caused a marked depolarization of motoneurons in the isolated rat spinal cord, which was almost insensitive to CPP and CNQX. Depolarizing responses to L-CCG-I were markedly decreased by reducing the temperature of the bathing fluid. Similar results were obtained in the case of trans-ACPD, which is a metabotropic glutamate receptor agonist, but the depolarizing action of L-CCG-I was more potent than that of trans-ACPD. In Xenopus oocytes injected with poly(A)+ mRNA extracted from the rat brain, L-CCG-I induced significant oscillatory chloride currents, suggesting that L-CCG-I is a potent agonist for metabotropic-type glutamate receptors.

Amino Acids, Dicarboxylic↗