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Biomedical subjects

K Arai

Publications and source records attributed to K Arai.

At least 433 records · Page 24Linked to original sources
PubMed1995

[The intrapulmonary metabolism of prostaglandin E1 in patients with pulmonary hypertension].

We investigated the intrapulmonary metabolism of prostaglandin E1 (PGE1), hemodynamics, oxygenation indexes (OI) and intrapulmonary shunt ratios (QS/QT) in patients with pulmonary hypertension (PH group, n = 7) and those with normal pulmonary artery pressure (N group, n = 5). PGE1 at a concentration of 20 approximately 60 ng.kg-1.min-1 was continuously administered intravenously to the patients in both groups for treatment. The intrapulmonary metabolism of PGE1 was calculated as 100 x (1--the concentration ratio of PGE1 in radial/pulmonary artery) %. The concentrations of PGE1 were measured by radioimmunoassay (DCC method) with the specific anti-PGE1 antibodies supplied by Ono Pharmaceutical Co. Hemodynamics were measured using a Swan-Ganz catheter, and OI and QS/QT were calculated from blood gas analyses. In the PH group, the intrapulmonary metabolisms of PGE1 decreased significantly compared with the N group. In addition, mPAP/mSAP in the PH group increased significantly compared with the N group regardless of PGE1 administration. There were no significant differences in OI and QS/QT between the two groups in spite of PGE1 administration. We concluded that the intrapulmonary metabolisms of PGE1 in patients with pulmonary hypertension were significantly decreased compared to the patients with normal pulmonary artery pressure. For this reason, it is important to monitor hypotension more carefully whenever we administer PGE1 to patients for the treatment of pulmonary hypertension.

Aged↗
PubMed1995

[Frontal type adrenoleukodystrophy: the progress of the white matter lesion--a neuroradiological and pathological study].

We studied the correlation between neuroradiological findings and pathological observations of white matter lesions in a patient with frontal type adrenoleukodystrophy. A 41-year-old man developed schizophrenic symptoms and generalized convulsions at the age of 40. Examination revealed baldness, loss of the axillary hair, stereotypical behavior, mutism, dysphagia echographia, right hemiparesis, and brisk reflexes in all four limbs with bilateral extensor plantar responses. Blood examination revealed a high concentration of very-long-chain fatty acids in plasma; the patient was diagnosed as having adrenoleukodystrophy. His condition continued to worsen, and gradually he became akinetic. He died of pneumonia at the age of 43. T1- and T2-weighted MR images distinguished three abnormal zones in the cerebral white matter in this case. In the first zone (Z1), the signal intensity was moderately high on T2-weighted images and slightly low on T1-weighted images; this zone was not enhanced with Gd-DTPA. In the second zone (Z2), the signal intensity was slightly high on T2-weighted images, while moderately low on T1-weighted images; Z2 was enhanced with Gd-DTPA. In the third zone (Z3), the signal intensity was markedly high on T2-weighted images and low on T1-weighted images; Z3 was not enhanced with Gd-DTPA. Z3 was located in the frontal pole; Z2 and Z1 were consecutively located in rostro-caudal fashion in the brain. The subsequent pathological study of the brain of this patient revealed the following findings: Z1 showed destruction of myelin with axonal sparing, Z2 showed numerous lipid-laden macrophages, demyelinated axons, and a vigorous perivascular mononuclear cell response, Z3 consisted of a dense mesh of glial fibrils and scattered astrocytes without any evidence of an active process. In this study, the correlation between MR images and pathological findings in adrenoleukodystrophy was clearly established. Single photon emission tomography with 99mTc-hexamethylpropyleneamine oxime, and positron emission tomography with 15O2 continuous inhalation technique showed a reduction in the regional cerebral blood flow (rCBF) and in the regional cerebral metabolic rate of oxygen (rCMRO2) in the cerebral cortex near the Z1 and Z3. A normal or slight increase of rCBF and a reduction of r CMRO2 was found in the cerebral cortex near the Z2. Coronal MR images showed that Z3 was located in the deep white matter, while Z2 and Z1 were consecutively located in an inner-outward fashion, suggesting that the demyelination process started in the cingulum and spread in an inner-outward fashion and progressed in rostro-caudal manner.

Adrenoleukodystrophy↗
PubMed1995

[Metabolic pathway of the degradation of macromolecules by lysosomal enzymes].

The lysosomes of most cells function principally in intracellular digestion. They contain several dozens of enzymes, mostly acid hydrolyases. Vacuolar-ATPase on lysosomal membrane establishes low-pH environment required for efficient expression of hydrolyase activity. Of several dozen disorders of human and various animals known to be due to lysosomal dysfunctions, most of the lysosomal storage diseases are of genetic origin. Metabolic pathways of intracellular macromolecules within lysosomes have been established from studies on the molecular and biochemical defects on lysosomal enzymes. In the lysosomal storage diseases most of all, the metabolic pathways of breakdown of lipids, glycosaminoglycans or oligosaccharides are severely affected. The degradation pathways of glycoproteins, proteoglycans, and glycolipids by lysosomal enzymes are described in this brief review.

Animals↗
PubMed1995

The concept of "template" assisted electronic medical record.

A new design for an electronic medical record with flexible template generation was developed. The "template" in this paper refers to one of the tools that calls a user's attention to entering the data items for each problem or to ordering tests when they are due. The template shows the patient's previous data and guides physicians to record the consistent description. Two kinds of medical data dictionaries are prepared. Data representations of signs, symptoms, laboratory tests, and other examinations are defined in the check items dictionary. The problem dictionary contains the possible patient problems with relation to check items and other kinds of related subjects. This system provides Problem Oriented Medical Record (POMR) and the graphical presentation of various patient data. The system was designed to establish a constant and integrated medical record.

Artificial Intelligence↗
PubMed1994

The transcription factor Sp1 is required for induction of the murine GM-CSF promoter in T cells.

The cis-acting region, GM-kappa B/GC-box (positions -95 and -73), within the murine GM-CSF gene promoter is required for maximal induction by stimulation with phorbol-12-myristate acetate (PMA) and calcium ionophore (A23187) in T cells. GM-kappa B defines a binding site for NF-kappa B, and GC-box defines a binding site for three (A1, A2, B) constitutive proteins. We report here that three copies of the GC-box can functionally compensate for the GM-kappa B/GC-box region, suggesting that the GC-motif can function independently of the GM-kappa B motif. The major GC-box binding activity A1 was purified and identified as the transcription factor Sp1. We show that depletion of Sp1 (A1) from nuclear extracts specifically decreases in vitro transcription activity on GM-CSF templates. Since the human GM-CSF promoter has a base difference within the GC-box, we speculate that this may explain why the human promoter is weak and that an upstream enhancer is required for the induction of the human GM-CSF gene.

Animals↗
PubMed1994

Escherichia coli PriA protein is essential for inducible and constitutive stable DNA replication.

Under certain conditions, Escherichia coli cells exhibit either of two altered modes of chromosomal DNA replication. These are inducible stable DNA replication (iSDR), seen in SOS-induced cells, and constitutive stable DNA replication (cSDR), seen in rnhA mutants. Both iSDR and cSDR can continue to occur in the absence of protein synthesis. They are dependent on RecA protein, but do not require DnaA protein or the oriC site. Here we report the requirement for PriA, a protein essential for assembly of the phi X174-type primosome, for both iSDR and cSDR. In priA1(Null)::kan mutant cells, iSDR is not observed after induction by thymine starvation. Replication from one of the origins (oriM1) specific to iSDR is greatly reduced by the priA1::kan mutation. cSDR in rnhA224 mutant cells deficient in RNase HI is also completely abolished by the same priA mutation. In both cases, SDR is restored by introduction of a plasmid carrying a wild-type priA gene. Furthermore, the viability of an rnhA::cat dnaA46 strain is lost at 42 degrees C upon inactivation of the priA gene, indicating the lethal effect of priA inactivation on those cells whose viability depends on cSDR. These results demonstrate that a function of PriA protein is essential for iSDR and cSDR and suggest the involvement of the PriA-dependent phi X174-type primosome in these DnaA/oriC-independent pathways of chromosome replication. Whereas ColE1-type plasmids, known to be independent of DnaA, absolutely require PriA function for replication, DnaA-dependent plasmid replicons such as pSC101, F, R6K, Rts1 and RK2 are able to transform and to be maintained in the priA1::kan strain.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1994

Structure of the gene encoding the alpha subunit of the human granulocyte-macrophage colony stimulating factor receptor. Implications for the evolution of the cytokine receptor superfamily.

The receptor for granulocyte-macrophage colony-stimulating factor (GM-CSF) is composed of at least two subunits, alpha and beta. In addition to the conserved cysteine residues and a "WSxWS" motif, the extracellular segments of both subunits have domains that are structurally related to a fibronectin type III domain. This structure is conserved in all members of the cytokine receptor superfamily. We isolated and characterized genomic DNA clones containing the entire coding sequences of the alpha subunit of the human GM-CSF receptor (hGMR alpha). The gene spans approximately 44 kilobases and has 13 exons. The major transcription initiation site was determined to be 195 base pairs upstream of the translation initiation site. The putative promoter region lacks a typical TATA motif and an Sp1 binding site, but contains a purine-rich stretch about 30 base pairs upstream of the transcription initiation site. This stretch is also found in the human interleukin 2 receptor gamma subunit and granulocyte colony-stimulating factor receptor genes. We compared the exon-intron organization of the hGMR alpha gene with other members of the cytokine receptor superfamily and found the genomic organizations to be remarkably well conserved. On the basis of these observations, we propose a model for evolution of this gene family.

Base Sequence↗
PubMed1994

Differential response of NF-kappa B1 p105 and NF-kappa B2 p100 to HTLV-I encoded Tax.

In a previous study we found that HTLV-I encoded Tax transactivator, which binds to NF-kappa B1 p105, suppresses p105-mediated I kappa B activity, thereby allowing entry of NF-kappa B p65 (RelA) and p50 into the nucleus. In the present report, we compared the effect of Tax on NF-kappa B2 p100, which also binds to Tax, with that of p105 in transfected COS7 cells. While p105 is processed to the DNA binding form, p50, processing of p100 was much less efficient both in the presence and absence of Tax. Both p105 and p100 showed I kappa B activity in sequestering NF-kappa B p65 into the cytoplasm. However, only p105-mediated I kappa B activity, and not that of p100, was inhibited by Tax. Chimeric molecules between p100 and p105 suggested that inefficient processing of p100 can be attributed to the Rel homologous domain, rather than to the ankyrin repeat domain. p100, but not p105, potently suppressed Tax- and p65-induced transaction of a GM-CSF promoter in Jurkat cells. Taken together, these results suggest that p105 and p100 may have distinct effects on Tax-induced transactivation events.

Amino Acid Sequence↗
PubMed1994

Characterization of NF(P), the nuclear factor that interacts with the regulatory P sequence (5'-CGAAAATTTCC-3') of the human interleukin-4 gene: relationship to NF-kappa B and NF-AT.

The P sequence of the human interleukin-4 (IL-4) gene, which was defined as a responsive element for phorbol 12-myristate 13-acetate and calcium ionophore (A23187) in Jurkat T cells, shares sequence similarity with the NF-kappa B and the NF-AT binding sites. We examined whether NF(P), a nuclear factor specific for the P sequence, is related to NF-kappa B and NF-AT. NF-kappa B (P65 or P65/P50 heterodimer) bound to the P sequence in electrophoretic mobility shift assays (EMSA) and activated transcription through the P sequence when expression plasmids were cotransfected with P sequence-driven reporter plasmids in Jurkat T cells. In EMSAs, NF(P) binding was inhibited by the unlabeled NF-AT binding site but not by the unlabeled AP1 binding site and purified NF-AT contained an activity that bound to the P sequence. Both mobility shift and sequence specificity of NF-AT were similar to those of NF(P) and only a small amount of P65 was detected in NF(P) in crude nuclear extracts. These results indicate that the component(s) of NF-AT has the potential to reconstitute NF(P) whereas NF-kappa B alone cannot account for NF(P) in crude extracts. Unlike NF-AT, NF(P) does not contain AP1 as its DNA binding component.

Base Sequence↗
PubMed1994

Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B/AP-1 in T cells.

Two cis-acting elements GM-kappa B/GC-box and CLE0, of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene are required for maximal induction in Jurkat T cells by costimulation with phorbol-12-myristate acetate (PMA) and Ca2+ ionophore (A23187). The GM-kappa B sequence is recognized by NF-kappa B, which is mainly induced by PMA. The CLE0 sequence interacts with factors, related to a PMA-induced AP-1 and a PMA/A23187-induced NF-AT. We examined whether signal transducing components in T cells can activate transcription of the GM-CSF gene. Cotransfection of NF-kappa B (p50/p65)- or AP-1 (c-Jun/c-Fos)-expression vectors into Jurkat cells with a luciferase reporter containing the GM-CSF promoter did not stimulate transcription from the GM-CSF promoter. In contrast, cotransfection with a combination of NF-kappa B and AP-1 significantly augmented transcription from the GM-CSF promoter containing the GM-kappa B/GC-box and the CLE0 (AP-1/NF-AT). Expression of a constitutively active calcineurin (CN), a Ca2+/calmodulin-dependent protein phosphatase, potentiated by two fold the transcriptional activation by NF-kappa B/AP-1. Both constitutively active forms of CN and protein kinase C (PKC) synergistically activated transcription from the GM-CSF promoter. These results suggest that cooperation among NF-kappa B-, AP-1- and NF-AT-binding sequences is required for induction of the GM-CSF gene through PKC- and Ca2+-signaling pathways downstream of T cell activation.

Animals↗
PubMed1994

Cytosol treated with GTP gamma S disintegrates lysosomes in vitro.

Cytosol that was treated with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) disintegrated lysosomes in a dose dependent manner, as detected by the release of preloaded fluorescein isothiocyanate-dextran from lysosomes. This phenomenon is a consequence of the two successive steps of incubation, (i) the treatment of cytosol with GTP gamma S, and (ii) the disintegration of lysosomes by the treated cytosol. The first step was specific for GTP gamma S and the effect of GTP gamma S was suppressed by GTP or GDP. The second step required ATP but it was not affected by bafilomycin A1. GTP gamma S treatment of lysosomes themselves did not induce their lysis. The lytic "factor(s)" produced in GTP gamma S-treated cytosol consisted of high molecular weight protein(s).

Adenosine Triphosphate↗
PubMed1994

Molecular cloning of a mouse counterpart for human TGF-beta type I receptor.

TGF-beta is a multifunctional polypeptide which is involved in the regulation of cell growth, differentiation, and immunomodulation. Its signaling receptors on the cell surface are postulated to be the type I (TGF beta RI) and type II receptors (TGF beta RII). Previously, TGF beta RII has been cloned and was found to be a receptor type serine/threonine kinase (RSK). In an attempt to isolate novel RSKs expressed in mouse ES cells, we obtained a clone designated as ESK2, which was very closely related to human TGF beta RI. The amino acid sequence of the intracellular domain is completely identical and the transmembrane domain is identical except for one residue. The extracellular domain is 90% homologous with a deletion and an insertion of four amino acid residues. ESK2 also binds to TGF-beta in the presence of TGF beta RII, indicating that ESK2 is the mouse counterpart for human TGF beta RI.

Amino Acid Sequence↗