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Biomedical subjects

F Kishi

Publications and source records attributed to F Kishi.

At least 19 recordsLinked to original sources
PubMed1999

Structural analysis of human SCC antigen 2 promoter.

The squamous cell carcinoma antigen (SCCA) has been used as a circulating tumor marker for the management of squamous cell carcinoma. SCCA consists of a small gene family of at least two in human genome (SCCA1 and SCCA2), which are tandemly arrayed on chromosome 18q21.3 and share 92% identical residues. SCCA expressions are tightly controlled in a tissue-specific manner. To investigate the role of SCCA2 in the cancer cells, we first isolated the human genomic clones, containing the promoter region of SCCA2 gene, and determined the nucleotide sequence surrounding the exon 1. The transcription start site was mapped by primer extension analysis, and a putative TATA box element was found in the 5'-flanking region. Other putative regulatory sequences, which include Ets binding sequence, NF-IL6 binding sequence and IRE consensus sequence, were also found in the region. Analysis of luciferase reporter gene expression in transient transfection showed that the promoter region of SCCA2 gene was located within the region from -424 to +47.

Antigens, Neoplasm↗
PubMed1998

Human natural resistance-associated macrophage protein 2: gene cloning and protein identification.

The Lsh/Ity/Bcg locus in the mouse genome regulates macrophage activation for antimicrobial activity against intracellular pathogens, and mouse Nramp1 (natural resistance-associated macrophage protein) gene was isolated as its candidate. The human NRAMP1 gene was subsequently isolated and its gene product was identified in macrophage/monocyte cells. Recently, a second Nramp gene, Nramp2, was found in mouse and human genomes. In the present study, we report the cloning and characterization of the human NRAMP2 gene, which is approximately 42 kb in length, containing 16 exons. The transcription start site was determined by 5'-RACE method, and the promoter was located between -246 bp to 145 bp in a region relative to the transcription start site, able to drive the luciferase reporter gene in HeLa cells. We also raised a polyclonal antibody against the glutathione S-transferase fusion protein containing the NH2-terminal 86 amino acids of human NRAMP2. The protein product of the human NRAMP2 gene is apparently present in human cultured cell lines as a 64 kDa protein recognized by this antibody, which is consistent with the molecular mass deduced from the human NRAMP2 cDNA.

Base Sequence↗
PubMed1998

Novel 31-amino-acid-length endothelins cause constriction of vascular smooth muscle.

We have reported that human chymase specifically cleaves big endothelins (ETs) at the Try31-Gly32 bond, and produces novel trachea-constricting 31-amino-acid-length ETs, ETs(1-31). In this study, we investigated the effect of synthetic ETs(1-31) on the contractile activity toward porcine coronary arteries and rat aortae. Although ETs(1-31) exhibited less potent vasoconstrictile activity in these tissues than 21-amino-acid-length ETs(1-21), or a similar extent, ET-1(1-31) caused significantly slower-developing and longer-lasting contraction than ETs(1-21). The ETA receptor antagonist, BQ485, completely inhibited the activity of ET-1(1-31). The ETB receptor antagonist, BQ788, also inhibited the activity of ET-1(1-31) toward rat aortae more efficiently than that ET-1(1-21). Therefore, trachea-constricting peptides ETs(1-31) play roles as vasoconstrictors in a different manner from ETs(1-21).

Animals↗
PubMed1998

Human natural resistance-associated macrophage protein is a new type of microtubule-associated protein.

Natural resistance-associated macrophage protein 1 (NRAMP1) is a putative membrane protein that dominates natural resistance to infection. An NRAMP1-glutathione S-transferase fusion protein was used to test the ability of the NRAMP1 NH2-terminal domain to bind to taxol-stabilized microtubules. Co-sedimentation analysis showed that the fusion protein binds to microtubules. Although the NH2-terminal domain of the NRAMP1 molecule has structural homology with the Pro-rich region of microtubule-associated protein 4 (MAP4), the presence of the MAP4 microtubule-binding domain fragment had little effect on the binding of the fusion protein to microtubules.

Animals↗
PubMed1998

Histamine H2-receptor-mediated nitric oxide release from porcine endothelial cells.

The involvement of histamine-receptor subtypes in histamine-induced release of nitric oxide (NO) from porcine aortic endothelial cells was studied. NO release was measured directly by using an NO electrode and by electron paramagnetic resonance (EPR) spin trapping. NO release induced by histamine (200 microM) was reduced in the presence of 2 microM cimetidine, an H2-receptor antagonist, but not altered by 2 microM pyrilamine, an H1-receptor antagonist. Histamine-induced NO release was significantly reduced by the addition of 20 microM of the Rp diastereomer of adenosine cyclic 3',5'-phosphorothioate (Rp-cAMPS), a membrane-permeable antagonist of cyclic adenosine monophosphate (cAMP). Application of 100 microM forskolin, an activator of adenylate cyclase, induced NO release from porcine aortic endothelial cells. Fura-2 acetoxymethylester (fura-2/AM) studies showed that addition of 100 microM histamine did not produce any significant increase in the use of free concentration of intracellular Ca2+. These results suggest that in porcine aortic endothelial cells, NO-mediated vasodilation might be caused by production of cAMP initiated through the histamine H2-receptor.

Animals↗
PubMed1998

Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins.

We report the novel role of human chymase in the production of bioactive 31-amino acid length endothelins (ETs), which may play a role in allergies and vascular diseases. In the bronchi of asthmatic patients, the vascular tissue in atherosclerosis, and the heart muscle in cardiac hypertrophy, both ET-like immunoreactivity and the accumulation of mast cells significantly increase. Chymase from human mast cells selectively cleaves big ET-1, -2 and -3 at their Tyr31-Gly32 bonds, and produces novel bioactive 31-amino acid length ETs, ETs(1-31), without any further degradation products. However, chymases from other species, human cathepsin G, and porcine alpha-chymotrypsin, degrade big ETs. ETs(1-31) at concentrations between 10(-9) M and 10(-7) M exhibited various contractile potencies in rat tracheae and porcine coronary arteries in a dose-dependent manner. Furthermore, ET-1(1-31) at concentrations between 10(-14) M and 10(-10) M caused a significant increase in the intracellular free Ca2+ concentration. The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET converting enzyme(s) or other chymotrypsin-type proteases and metallo-endopeptidases, because the contractile activity was not significantly inhibited on treatment with inhibitors of these proteases prior to the addition of ET-1(1-31).

Animals↗
PubMed1998

[Evaluation on the clinical background on early death in patients with pulmonary tuberculosis during the past five years].

We evaluated the clinical background of early death (within 3 months after admission to our hospital) in patients with active pulmonary tuberculosis during the past five years (1992-1996). Among 65 active pulmonary tuberculosis patients who died during the past five years, 32 (49%) died directly of tuberculosis. Thirteen (41%) of those 32 patients died of acute respiratory failure and 9 patients (28%) died in emacitation state. Twenty two patients (69%) died within 3 months after admission to our hospital (the early death group) and 10 patients (31%) died after 3 months (the late death group). Thirteen patients (59%) in the early death group died of acute respiratory failure. On the other hand, none in the late death group died of acute respiratory failure but 4 patients died of chronic heart and/or respiratory failure and 4 patients died in emarciation state. Compared to the patients in the late death group, more patients in the early death group had long total delays (patient's and doctor's delays), had coexisiting diseases, had fallen into acute respiratory failure, and were under malnutrition. We evaluated the nutritional condition of patients using the Onodera's PNI (Prognostic Nutritional Index; 10 x serum almumin concentration + 0.005 x peripheral lymphocyte count) and the PNI value was lower among the patients in the early death group than among those in the late death group. To prevent death due to tuberculosis, we emphasize that it is important to start anti-tuberculosis therapy before patients fall into acute respiratory failure and/or malnutrition.

Acute Disease↗
PubMed1997

Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells.

Chymase from human mast cells selectively cleaved big endothelins (ETs) at the Tyr31-Gly32 bond and produced novel trachea-constricting 31-amino acid-length endothelins, ETs(1-31), without any further degradation products. Chymases from other species, such as the enzymes from rat connective tissue and mucosal mast cells, and the other chymotrypsin-like proteases examined degraded big ETs. ETs(1-31) exhibited various contractile potencies as to the rat trachea in comparison with 21-amino acid-length endothelins, ETs(1-21), and big ETs: ET-1(1-21) > ET-1(1-31) > big ET-1; ET-2(1-31) > ET-2(1-21) > or = big ET-2; ET-3(1-21) > or = ET-3(1-31) > or = big ET-3. Among the ETs(1-31), ET-2(1-31) was the most potent constrictor, its potency being similar to that of ET-1(1-21) and stronger than that of ET-2(1-21). The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET-converting enzymes or other chymotrypsin-type proteases and metalloendopeptidases, because the contractile activity was not inhibited significantly on treatment with inhibitors of these proteases before the addition of ET-1(1-31). Inhibitors of chymotrypsin-type serine proteases, on the contrary, significantly enhanced the contractile activity exhibited by ET-1(1-31) and big ET-1, but not that by ET-1(1-21). These results suggest that protease(s) on the surface of the rat trachea tends to degrade ETs(1-31) and big ETs, and thereby reduces their contractile activity. Taken together, the results suggest that trachea-constricting ETs(1-31) generated by human chymase may play a role in the hyper-responsive airway in allergic inflammation.

Animals↗
PubMed1997

Expression of NRAMP1 molecule in human peripheral blood leukocytes.

Natural resistance or susceptibility of host to infection with several intracellular pathogens, such as Mycobacterium, Salmonella and Leishmania, is controlled in mice by the expression of a single dominant gene locus designated Lsh/Ity/Bcg. Natural resistance-associated macrophage protein gene 1 (Nramp1) was isolated as a candidate gene. Nramp1 gene encodes a 60 kDa polypeptide with 10-12 potential transmembrane domains and an evolutionary conserved consensus transport motif. The present study shows that the human NRAMP1 gene is expressed in all established hematopoietic cell lines examined, including monocytes/macrophages and B- and T-lymphocytes. In contrast, cell type-specific expressions are observed in human peripheral blood leukocytes. NRAMP1 expression is very low level in granulocytes. B- and T-lymphocytes are equivalent in the level of NRAMP1 expression. Notable expression of NRAMP1 gene can be detected in the monocyte population. These results have important implications for the host defence mechanisms and the pathogenesis of intracellular pathogens which are recognized and ingested by the mononuclear phagocyte system including monocytes/macrophages.

Animals↗
PubMed1997

Signal averaged electrocardiogram after exercise in patients with mitral valve prolapse.

While late potentials are correlated with an increased incidence of ventricular tachycardia, they are not necessarily a good predictor of ventricular electrical instability in patients with mitral valve prolapse (MVP). Our objective was to determine whether the signal averaged electrocardiogram (SAECG) after exercise can discriminate groups with a higher frequency of ventricular arrhythmia from those without. The SAECG was recorded before and after treadmill exercise in 20 normal subjects (N group), 20 patients with MVP (MVP group) and 10 patients with old myocardial infarction (MI group). Five patients (25%) in the MVP group and two patients (33%) in the MI group had late potentials before exercise. Late potentials in the MI group did not disappear with exercise, whereas they disappeared with exercise in two patients in the MVP group. The results suggest that the late potentials observed in patients with MVP differ in nature from those with old myocardial infarction and are not always related to lethal arrhythmia.

Adult↗
PubMed1997

[Clinical study of the application of the concepts of systemic inflammatory response syndrome (SIRS) in liver cirrhosis with or without hepatocellular carcinoma with upper gastrointestinal hemorrhage--a retrospective study].

The retrospective study was aimed at assessing the usefulness of the application of the criteria of SIRS for identifying a subset of patients with higher mortality in 22 cases (21 patients) of liver cirrhosis with upper gastrointestinal hemorrhage (GIH) and 16 cases (14 patients) of liver cirrhosis with hepatocellular carcinoma with upper GIH. The following results were obtained; (1) The incidence of SIRS on upper GIH was 66%. (2) The mortality rate in patients with SIRS on GIH was significantly higher than in patients with non-SIRS on GIH in 60 days after GIH was significantly higher than in patients with non-SIRS on GIH in 60 days after GIH (50% vs. 8%; p < 0.01). (3) The rate of patients who met four criteria of SIRS on GIH or during admission and of patients whose durations of SIRS was over 5 days was significantly higher in the died patients with SIRS on GIH than in the survived patients with SIRS on GIH (67% vs. 0%; p < 0.01, 67% vs. 0%; p < 0.01, respectively). These results suggested that the application of the criteria of SIRS was useful for identifying a subset of patients with higher mortality in chronic liver disease with GIH.

Adult↗
PubMed1997

[An observation on tuberculosis associated with HIV infection in Japan].

OBJECTIVE: To observe the reported cases of tuberculosis (TB) with HIV infection in Japan, in terms of their main clinical features and related factors. METHODS: A voluntary reporting network has been organized by the authors who are specialists of TB or respiratory medicine in tuberculosis institutions located roughly all over the country. The members have been encouraged to report not only their own cases but cases seen by their friends or in other institutions. RESULTS: By the end of 1996, a total of 71 cases have been reported of which 59 were TB and 12 NTM cases. Nationality of the cases were; Japan 48, Other Asian countries 16, Others 7. All of the NTM cases were Japanese. 30% of the cases were aged less than 30 years, 24% were thirties, 24% forties, 17% fifties and 6% were those aged 60 years or older. The cases were clearly younger than the TB cases in the national TB registry, and older than HIV-infected persons as known from the HIV surveillance system. 97% of the TB cases were bacteriologically confirmed cases. Eight of NTM cases were positive for MAC, others for M.kansasii. 42% of the cases had extra-pulmonary disease, including disseminated infections seen among 19%. Of TB cases 25% were excreting bacilli resistant to any of the anti-TB drugs which was higher than in the case of general TB population (10-15%). 11% of TB cases had past history of TB treatment. The cases had severe immunological impairment, 79% of the cases having CD4+ cell count less than 100. The route of HIV infection were; 51% heterosexual, 13% homosexual, 13% through blood preparations, etc. DISCUSSION: Although there may be many cases not included in this observation, it is considered to well reflect the real situation of the problem of Japan. More attention should be paid to HIV infection of the patients in the clinical practice of TB in Japan.

AIDS-Related Opportunistic Infections↗
PubMed1996

Intracellular and extracellular Ca2+ regulate histamine-induced release of nitric oxide in vascular endothelial cells as shown with sensitive and selective nitric oxide electrodes.

The effects of various agents that alter the intracellular Ca2+ concentration and the extracellular Ca2+ concentration on histamine-induced release of nitric oxides (NO) from porcine aortic endothelial cells were studied using NO electrodes. The NO release induced by application of histamine (200 microM) in Ca(2+)-free solution was similar to that in solution with a normal Ca2+ concentration on its first application, but reduced on its second application. NO release was also suppressed by 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA), which lowers the intracellular Ca2+ concentration, and was completely inhibited by Co2+, but it was not affected by verapamil, a voltage-dependent Ca2+ channel blocker. These results suggest that Ca2+ release from intracellular stores might play an important role in NO production, that influx of extracellular Ca2+ is required to refill the stores, and that this Ca2+ influx is not through voltage-dependent Ca2+ channels.

Animals↗
PubMed1996

Structural analysis of human natural resistance-associated macrophage protein 1 promoter.

Natural resistance-associated macrophage protein gene 1 (Nramp1) was isolated as a candidate for the mouse gene locus Lsh/Ity/Bcg, which regulates macrophage activation for antimicrobial activity against intracellular pathogens. To investigate the structural and functional organization of the human homologue, NRAMP1, the overlapping genomic clones encompassing NRAMP1 were isolated. These clones spanned approximately 35 kb in size and the nucleotide sequence of 3779 bp of the 5' flanking region has been determined. The transcription start site was mapped by primer extension analysis. A TATA box element and the transcription regulatory elements in the acute phase reaction were found.

Base Sequence↗
PubMed1996

Location of NRAMP1 molecule on the plasma membrane and its association with microtubules.

Natural resistance to infection with intracellular parasites, such as Leishmania, Salmonella, and Mycobacterium, is controlled in mice by the expression of a single dominant gene locus designated Lsh/Ity/Bcg. Natural resistance-associated macrophage protein gene 1 (NRAMP1) was isolated as a candidate gene. NRAMP1 encodes an M(r) 60000 polypeptide with 10-12 potential transmembrane domains and an evolutionary conserved consensus transport motif. The present study shows that the human NRAMP1 molecule is expressed in all cell lineages of macrophage/monocyte and B- and T-lymphocytes. Immunohistochemical analysis using antihuman NRAMP1 antibody provides the direct evidence that the NRAMP1 molecule is located and distributed on the plasma membrane. An NRAMP1-glutathione S-transferase (GST) fusion protein was used to affinity-purify a protein, bound to the NH2-terminal cytoplasmic domain of NRAMP1. It was found that the NRAMP1 molecule was associated with alpha- and beta-tubulin of microtubules. These results suggest that NRAMP1 may function as a molecule, possessing the abilities of membrane-anchoring and microtubule-binding, for the microtubule-mediated transport of vesicles and be a new class of microtubule-associated proteins.

Amino Acid Sequence↗
PubMed1996

A 90-year old patient with atrial septal defect and sinus rhythm.

A 90-year old patient with an atrial septal defect (ASD) and sinus rhythm, but no history of atrial fibrillation of heart failure is presented. Literature searches revealed no similar report of such a case. In addition, this patient represents the oldest documented patients with ASD associated and sinus rhythm.

Age Factors↗
PubMed1996

[Home oxygen therapy (HOT) in patients with pulmonary tuberculosis sequelae--comparison between patients medically treated and those surgically treated].

In Japan there are about 40,000 patients under home oxygen therapy (HOT), of whom about 30 to 40% are pulmonary tuberculosis sequelae (TBS). These patients can be divided into three groups depending on the treatments they had, Group 1: those who had medical treatments only, Group 2: those who had artificial pneumothorax, and Group 3: those who had thoracoplasties or other surgical treatments. The purpose of this study was to observe the distributions and possible differences in the survival rates among these groups. The study included 1537 patients with TBS under HOT followed at National Hospitals and Sanatoriums nationwide in Japan. In 819 patients the treatments were specified and of those 354 were in Group 1, 29 in Group 2, and 436 in Group 3, so that the proportion of surgically treated patients in PTS was estimated between 28.4% (436/ 1537) to 53.2% (436/819). The ages at the onset of tuberculosis, at the start of HOT and the intervals in between were 36.6, 66.2 and 29.8 in Group 1, and 26.8, 65.5, and 38.1 in Group 3 respectively. Though the ages at the start of HOT were the same, those at the onset of tuberculosis were about ten years younger in Group 3 than in Group 1. Comparing Group 1 and 3, the survival rates after the initiation of HOT (Kaplan-Meier method) was better in Group 2 (surgically treated) than in Group 1 (medically treated). It is speculated that the reason could be a better preservation of the function of the remaining lung in the surgically treated and a higher incidence of obstructive impairments in the medically treated patients.

Adolescent↗