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Biomedical subjects

A Nakata

Publications and source records attributed to A Nakata.

At least 55 records · Page 3Linked to original sources
PubMed1997

Strain-related differences in Sephadex bead-induced airway hyperresponsiveness and inflammation in rats.

OBJECTIVE: The aim of this study was to compare Sephadex G-200 (Sephadex)-induced airway hyperresponsiveness (AHR) and pulmonary eosinophilia among some rat strains. MATERIALS: Sprague-Dawley (SD), Brown-Norway (BN), Fischer 344 (Fischer), Lewis and Wistar-Kyoto (WKY) rats were used. METHODS: Sephadex (0.5 mg/animal) was intravenously administered on days 0, 2 and 5. Measurement of AHR using serotonin and bronchoalveolar lavage (BAL) was performed on day 7. RESULTS: The Lewis strain exhibited significant AHR to Sephadex but the BN, Fischer and WKY strains did not. Additionally, the degree of AHR in Lewis rats was smaller than in SD rats throughout the study. Eosinophils in BAL fluid, however, increased in each strain, and the magnitude of the response was BN > Lewis > WKY > Fischer. Both the AHR and pulmonary eosinophilia in Lewis rats were inhibited by dexamethasone (0.1 mg/kg, p.o. x3). CONCLUSION: These results indicate that the Lewis rat is a useful strain for analysis of the mechanism of Sephadex-induced AHR and airway inflammation.

Animals↗
PubMed1997

Decreased cytotoxic lymphocyte counts in alexithymia.

BACKGROUND: Alexithymia is a psychological trait characterized by a difficulty in verbalizing feelings, which has been associated with a number of illnesses, including bronchial asthma and cancer. METHODS: In order to understand how psychological variables such as alexithymia affect physical health, we compared the lymphocyte subsets of men (n = 97, mean 30.6) rated as high and low alexithymic when measured by the Toronto Alexithymia Scale (TAS). We analyzed our data by considering alexithymia a categorical variable, using TAS scores of 62 and below, and 74 and above, and by considering alexithymia a continuous variable, using the mean TAS score (64.01) separating high from low alexithymia. RESULTS: When alexithymia was considered a categorical variable, highly alexithymic men had significantly lower numbers of the most cytotoxic natural killer (NK) subset, (CD57-CD16+ cells). When alexithymia was considered a continuous variable, in addition to the NK subset, killer effector T cell (CD8+CD11a+ cells) count was also significantly lower. These results were obtained after controlling for possible effects of smoking and alcohol intake. CONCLUSIONS: These results suggest that the negative modulation of cellular immunity, especially the cytotoxic lymphocytes, may be one mechanism which, combined with other factors that have a negative effect on the immune system such as stress, results in the association between alexithymia and ill health. It is suggested that future studies should, in addition to cell counts, attempt to identify the effects of psychological variables on the cytolytic activity of cytotoxic lymphocytes. Furthermore, follow-up studies should monitor the subjects over the years to demonstrate that alexithymia-mediated negative modulation of the immune system results in clinical pathologies.

Adult↗
PubMed1997

Effects of job strain on helper-inducer (CD4+CD29+) and suppressor-inducer (CD4+CD45RA+) T cells in Japanese blue-collar workers.

BACKGROUND: The effects of job strain on helper-inducer (CD4+CD29+) T cells and suppressor-inducer (CD4+CD45RA+) T cells are not clear. METHODS: The subjects were 65 male blue-collar workers in a chemical plant in Japan. Perceived job stressors were assessed using the Japanese version of Job Content Questionnaire, i.e., job demands, job control, supervisor support and coworker support. Blood samples were taken from these subjects, and number and percentage of total lymphocytes were calculated for total T cells, helper (CD4+) T cells, suppressor/cytotoxic (CD8+) T cells, helper-inducer (CD4+CD29+) T cells and suppressor-inducer (CD4+CD45RA+) T cells using the double-staining fluorescence. RESULTS: Job control significantly and positively correlated with number and percentage of helper-inducer (CD4+CD29+) T cells, after controlling for age, number of cigarettes per day and blood lead concentration (Spearman's partial correlation, p < 0.05), while job demands, supervisor support or coworker support did not (p > 0.05). The job strain index, i.e., the ratio of job demands to job control, significantly and negatively correlated with the percentage of helper-inducer (CD4+CD29+) T cells (p < 0.05). None of the job stress scales significantly correlated with number or percentage of suppressor-inducer (CD4+CD45RA+) T cells (p > 0.05). CONCLUSIONS: It is suggested that higher job strain or lower job control is associated with a decrease in helper-inducer (CD4+CD29+) T cells in Japanese blue-collar workers.

Adult↗
PubMed1997

Successful transfer of late phase eosinophil infiltration in the lung by infusion of helper T cell clones.

Bronchial asthma is characterized by chronic eosinophilic inflammation of the bronchial mucosa. Accumulating evidences suggest that activated T cells and T cell cytokines play critical roles in the local accumulation and activation of eosinophils. To further delineate the critical role of T cells on asthma, we tested the possibility whether eosinophilic inflammation of the bronchial mucosa is induced by transferred T cell clones, in the absence of antigen-specific immunoglobulins (IgE, A, and G). Ovalbumin-specific Th2 clones were established and cytokine profiles were determined. Eosinophilic inflammation accompanied with airway hyperresponsiveness occurred only when unprimed mice were transferred with IL-5 producing Th2 clones and challenged by the inhalation of relevant antigen. Increase of IL-5 concentration in bronchoalveolar lavage fluid (BALF) was detected after the challenge, indicating the local production of cytokines by the transferred T cells, and preceded the appearance of the airway eosinophilia. Eosinophil infiltration was completely suppressed by the administration of anti-IL-5 neutralizing antibody, indicating the essential role of IL-5 in this model. The intensity of the eosinophil accumulation in vivo correlated well with the capacity of the T cell clones to produce IL-5 in vitro. We concluded that the existence of IL-5-producing helper T cells is sufficient for the development of the eosinophilic inflammation at the bronchial mucosa upon inhalation challenge of the relevant antigen.

Animals↗
PubMed1996

Localization of heparin-binding epidermal growth factor-like growth factor in human coronary arteries. Possible roles of HB-EGF in the formation of coronary atherosclerosis.

BACKGROUND: Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a newly identified member of the EGF family. Our previous in vitro studies showed that HB-EGF is a potent mitogen and chemoattractant for vascular smooth muscle cells (SMCs), suggesting the role of HB-EGF in the pathogenesis of atherosclerosis. The purposes of the present study were to investigate the localization of HB-EGF in both normal and atherosclerotic human coronary arteries and to elucidate the possible roles of this growth factor in the formation of atherosclerotic lesions. METHODS AND RESULTS: The immunohistochemical localization of HB-EGF, SMCs, macrophages, and EGF receptors (EGFRs) was examined in human coronary arteries obtained at autopsy. The medial SMCs of coronary arteries in neonates, infants, and children consistently synthesized HB-EGF protein. In normal adults, however, the relative number of HB-EGF-positive medial SMCs decreased gradually with age after about 30 years of age. In nonatherosclerotic coronary arteries with diffuse intimal thickening, SMCs of the intima, especially those located in the area of the medial side of the intima, were strongly positive for HB-EGF protein. In atherosclerotic plaques of coronary arteries with eccentric intimal thickening, both SMCs and macrophages in and around the core lesions, in addition to the intimal and medial SMCs located adjacent to the plaque, produced HB-EGF protein. A strong immunostaining of EGFRs was observed in these SMCs, suggesting a close association of HB-EGF and EGFR expression. CONCLUSIONS: These data suggest that HB-EGF might play important roles in the migration of SMCs from the media to the intima, the proliferation of intimal SMCs, and the interaction between SMCs and macrophages in the process of coronary atherogenesis.

Adult↗
PubMed1996

Facilitatory role of somatostatin via muscarinic cholinergic system in the generation of long-term potentiation in the rat dentate gyrus in vivo.

We investigated whether somatostain modulates the generation of long-term potentiation (LTP) in rat perforant path-dentate gyrus synapse in vivo. When somatostatin was injected intracerebroventricularly (i.c.v.) 20 min prior to the tetanus, the intensity of LTP increased dose dependently. Synaptic potential evoked by a low-frequency test stimulation, however, was not altered by somatostatin. We next tested whether the LTP-augmenting effect of somatostain is mediated by cholinergic activation, because somatostatin was demonstrated to promote acetylcholine release in rat hippocampal slice. Pirenzepine (50 nmol/rat), a muscarinic M1 receptor antagonist, did not affect the tetanus-induced LTP by itself. But when it was co-applicated with the somatostatin (50 ng/rat) 20 min before tetanus, it completely abolished the LTP-augmenting effect of somatostatin. Then we examined the effect of octreotide, a potent agonist specifically binding to somatostatin receptor subtypes 2 and 4, on the generation of LTP. Octreotide (500 ng/rat) also facilitated the intensity of LTP. These results suggest that somatostatin facilitates the generation of perforant path-dentate gyrus granule cell LTP by activating the muscarinic cholinergic receptor and the effect of somatostatin is induced, at least partly, by somatostatin receptor subtypes 2 and 4 in vivo.

Animals↗
PubMed1996

DNA binding of PhoB and its interaction with RNA polymerase.

We have identified the DNA-binding domain (DBD) of an Escherichia coli activator protein PhoB as its C-terminal 91 residues. Four amino acid positions in the PhoB DBD are found important for interaction with the RNA polymerase holoenzyme that contains the sigma 70 subunit. Assuming that the PhoB DBD is structurally similar to the histone H5 DBD, the four positions are placed around the turn region that connects two putative helices, 2 and 3 (helix 3 is likely to be the recognition helix). The binding sites of PhoB, three with the sequence TGTCA and one of TTACA, are identified in the pstS promoter. The pstS promoter has intrinsic bending (or bendability), which is much enhanced upon binding PhoB. On the basis of the above, some aspects of the PhoB-DNA-RNA polymerase interaction are discussed.

Amino Acid Sequence↗
PubMed1996

Effects of pravastatin on plasma and urinary mevalonate concentrations in subjects with familial hypercholesterolaemia: a comparison of morning and evening administration.

In order to determine whether there is a difference in the effect of the hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin on cholesterol synthesis between the morning and the evening, we studied the 24-h profile of mevalonate in plasma and urine in 11 subjects with heterozygous familial hypercholesterolaemia. In study 1, eight subjects with familial hypercholesterolaemia took pravastatin (20 mg) once in the morning, and another 20-mg dose in the evening after a 1-week wash-out period. In study 2, five subjects with familial hypercholesterolaemia took pravastatin (20 mg per day) in the morning on 3 consecutive days and on 3 days in the evening after a 1 day wash-out. Plasma mevalonate concentrations were reduced at 9 h and 5 h after pravastatin administration in the morning and the evening, respectively. Urinary mevalonate excretion was significantly reduced at 4-8 h after pravastatin administration in the morning (51 vs 19 nmol.h-1) and at 4-16 h after pravastatin administration in the evening (56 vs 27 nmol.h-1). Daily urinary mevalonate excretion was equally and significantly reduced by pravastatin in the morning or evening. In conclusion, we found that morning and evening administration of pravastatin caused equal reductions in plasma and urinary mevalonate concentrations.

Administration, Oral↗
PubMed1996

An Economic Analysis of Water and Sanitation Infrastructure Improvements in the Colonias of El Paso County, Texas.

The authors conducted a cost-benefit analysis of a project to improve water supply and sanitation infrastructure in a rural community (colonia) along the United States-Mexico border. The present value of total costs in the scenario without improvements was $42,937,507, compared with net costs with improvements of $34,600,800. It is estimated that improved access to safe drinking water and solid waste sanitation prevented 155 cases of hepatitis A and 5,165 cases of gastrointestinal illness over 26 years and saved $846,541 in associated health care costs, approximately 10% of the total estimated savings. The majority of benefits was in the form of time savings and increased land values. The authors did not consider the value of improving environmental conditions for future generations and preventing communicable disease epidemics associated with poor sanitation. Accurate value estimates for these benefits might strengthen the argument for undertaking similar infrastructure-improvement projects in the colonias and in other underdeveloped rural areas of the United States. cost-benefit analysis; water supply and sanitation; health care costs; disease-prevention effectiveness Hanley & Belfus, Inc. Int J Occup Environ Health 1077-3525 2 3 1996 July/September Decreases in Subpopulations of T Lymphocytes and Natural Killer Cells in the Blood of Retired Chromate Workers 222 225 EN Takeshi Tanigawa Shunichi Araki Department of Public Health, Faculty of Medicine, University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan. Akinori Nakata Takaharu Araki Susumu Sakurai To examine the effects of past exposure to chromates on lymphocyte subpopulations in man, the authors measured subpopulations of T lymphocytes and natural killer (NK) cells by flow cytometry together with B lymphocytes in blood samples from 27 male workers and 22 healthy controls. All subjects were nonsmokers. The numbers of CD4+CD45RA+ (suppressor-inducer), CD8+ (suppressor/cytotoxic) and total T lymphocytes, CD16+CD57+ NK cells, and total lymphocytes in the blood of chromate workers were significantly smaller than those in the blood of healthy controls (analysis of covariance with age as a covariate). It is suggested that suppressor-inducer and suppressor/cytotoxic T lymphocytes and NK cells with intermediate NK cell activity are most susceptible to the effects of past exposure to chromates as compared with other lymphocyte subpopulations such as B and CD4+CD29+ T lymphocytes.

Journal Article↗
PubMed1996

Interventricular septal dissection in a patient with an old myocardial infarction.

We observed an unusual case of interventricular septal wall dissection in a patient with a prior myocardial infarction. Echocardiography, magnetic resonance imaging, and left ventriculography revealed separation of the right-side and left-side walls of the interventricular septum with an accessory chamber between the two walls. Morphologic findings were consistent with interventricular septal dissection.

Diagnosis, Differential↗
PubMed1995

Autophosphorylation and activation of transcriptional activator PhoB of Escherichia coli by acetyl phosphate in vitro.

The PhoB protein, the transcriptional activator for the genes belonging to the phosphate regulon in Escherichia coli, was autophosphorylated in the presence of acetyl phosphate (acP) in vitro. The properties of phospho-PhoB, such as stability upon acid or alkali treatment and activating pstS transcription by RNA polymerase holoenzyme, were the same as those of phospho-PhoB produced from phospho-PhoR or phospho-PhoM. These results indicate that PhoB is an enzyme that catalyzes its own phosphorylation using acP, a low-molecular-weight metabolic intermediate.

Bacterial Proteins↗
PubMed1995

Mutational analysis of the role of the first helix of region 4.2 of the sigma 70 subunit of Escherichia coli RNA polymerase in transcriptional activation by activator protein PhoB.

Transcription of the genes belonging to the phosphate (pho) regulon in Escherichia coli requires the specific activator protein PhoB, in addition to RNA polymerase containing the major sigma factor, sigma 70, which is encoded by rpoD. We previously isolated two mutant sigma 70s (D570G and E575K) that were specifically defective in transcribing the pho genes. The mutated sites were located near and within the first helix of the helix-turn-helix (HTH) motif or region 4.2 of sigma 70. To study further the role of the first helix of the HTH motif of sigma 70 in transcriptional activation by PhoB, we made a series of rpoD mutations that alter the motif and purified the mutant sigma 70 proteins. RNA polymerases containing the mutant sigma 70s Y571A, T572L, V576T, K578E and F580V showed reduced in vitro transcription from the pstS promoter, a representative pho promoter, in the presence of PhoB, whereas RNA polymerase containing another mutant sigma 70 (E574K) showed enhanced transcription from the promoter. Transcription from the activator-independent tac promoter and the pBR-P4 promoter, which is independent of PhoB and requires cAMP-CRP (cAMP receptor protein) for transcription, was affected at most only marginally by these sigma 70 mutations. These results provide further evidence that the first helix plays an important role in the specific interaction between RNA polymerase and PhoB protein bound to the pho promoters in transcriptional activation.

Amino Acid Sequence↗
PubMed1995

Overproduction, purification, and diagnostic use of the recombinant HIV-1 Gag proteins, the precursor protein p55 and the processed products p17, p24, and p15.

HIV-1 Gag protein precursor p55, and its processed products, p17, p24, and p15 were overproduced in Escherichia coli and purified to near homogeneity. To study the antigenic properties and the potentiality as the diagnostic and prognostic reagents, varying amounts of the purified Gag proteins were dotted onto the polyvinylidene difluoride membrane and reacted with 40 sera of HIV-1-infected individuals (35 AC, 1 ARC, and 4 AIDS patients) and 10 sera of normal healthy donors. p55 reacted with 40 (100%) sera of HIV-1 carriers, while p17, p24, and p15 reacted with 37 (92.5%), 35 (87.5%) and 34 (85%) of the 40 sera of HIV-1 carriers, respectively. On the whole, the reaction of p55 was especially strong and that of p15 was the weakest. p55 showed the strongest reaction among the four Gag proteins with all specimens, and it showed a positive reaction with a carrier serum with which none of the processed Gag proteins showed a positive reaction. Therefore, p55 is the most useful antigen among the four Gag proteins for detection of the Gag antibodies and may even be one of the most useful antigens for the diagnosis of HIV-1 infection.

Chromatography, Gel↗
PubMed1995

Three antigenic regions in p17 of human immunodeficiency virus type 1 (HIV-1) revealed by mouse monoclonal antibodies and human antibodies in HIV-1 carrier sera.

We investigated the murine antibody response to recombinant p17 (rp17) of human immunodeficiency virus type 1 (HIV-1) and the human antibody response directed to p17 in HIV-1 infection. Three large peptides covering residues 12-29, 53-87 and 87-115 of p17 were synthesized. The cysteine residues 57 and 87 of peptide 53-87 were reoxidized to form a disulfide bridge. Eighteen out of 19 murine monoclonal anti-rp17 antibodies had relatively high affinities (KA = 1.9 x 10(5)-1.4 x 10(8) M-1) with one of the 3 p17 peptides in the liquid phase. Each monoclonal antibody reacted only with one particular peptide and had no reactivity with the other 2 p17 peptides. All the monoclonal antibodies reacted with rp17 in the liquid phase with a reasonable degree of affinity (KA = 2.0 x 10(5)-1.8 x 10(7) M-1). Four HIV-1 carrier sera, which were positive in ELISA using rp17 as the antigen, reacted positively in an ELISA using 3 p17 peptides which were used to titrate murine monoclonal antibodies. Murine monoclonal antibodies having specificity for the 3 p17 peptides stained live HIV-1-infected cells by means of indirect membrane immunofluorescence, irrespective of their specificity. This suggests that the various portions of p17 (at least 3 regions of p17) were exposed on the surface of live infected cells, probably as short polypeptide chains.

Amino Acid Sequence↗
PubMed1995

Reduced uptake of oxidized low density lipoproteins in monocyte-derived macrophages from CD36-deficient subjects.

To clarify the physiological roles of CD36 as an oxidized low density lipoprotein (OxLDL) receptor, we analyzed the monocyte-derived macrophages from normal and two CD36-deficient subjects, since we identified the molecular abnormalities (Kashiwagi, H., Y. Tomiyama, Y. Kosugi, M. Shiraga, R. H. Lipsky, Y. Kanayama, Y. Kurata, and Y. Matsuzawa 1994. Blood. 83:3545-3552; and Kashiwagi, H., Y. Tomiyama, S. Honda, S. Kosugi, M. Shiraga, N. Nagao, S. Sekiguchi, Y. Kanayama, Y. Kurata, and Y. Matsuzawa. 1995. J. Clin. Invest. 95:1040-1046). Scatchard analysis of 125I-OxLDL binding showed a linear plot and the maximum binding was lower by approximately 40% in the macrophages from subjects with CD36 deficiency than those from normal controls. Competition studies showed that the uptake of 125I-OxLDL was suppressed by OKM5, an antibody against CD36, by 53% in normal control macrophages, but not in the CD36-deficient macrophages. After incubation with OxLDL for 24 h, cholesteryl ester mass accumulation was reduced by approximately 40% in the macrophages from CD36-deficient subjects than those from normal controls. These results suggest that CD36 is one of the physiological receptors for OxLDL. Since specific binding of OxLDL was only reduced by approximately 40% in spite of the complete deficiency of CD36, several other receptors also may have some role in OxLDL uptake. Further studies will be needed to assess the quantitative role of CD36 in foam cell formation in vivo.

Adult↗
PubMed1995

Limited impairment of learning performances in mice treated with cysteamine.

Cysteamine has been reported to disturb learning performance in rats. Our study was made to determine if this is also true in mice. Adult male ddY mice were subjected to a battery of learning tests following our standard experimental protocols. Cysteamine injected 30 min prior to the learning trial dose-dependently increased the number of errors in the testing trial of step-down test, and its effect was statistically significant at a dose of 200 mg/kg. In the lever press test, 200 mg/kg injection of cysteamine also suppressed the conditioned avoidance rate. However, no significant changes were observed in other tests. These results suggest that the learning disorder induced by cysteamine in mice is restricted to a specific type of behavioral performance. In conclusion, the mechanism by which cysteamine generates learning deficiency in mice may differ from that in rats.

Animals↗
PubMed1995

Distal vasoconstriction following coronary angioplasty--comparison of emergent and elective PTCA.

To examine the occurrence of distal vasoconstriction following primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction, quantitative coronary angiography was performed during and after acute myocardial infarction. An assessment of coronary artery vasoconstriction was made in patients undergoing primary and elective PTCA. The primary PTCA group was subdivided into two groups based on initial antegrade flow characteristics: group 1 (TIMI grade flow 0/1) and group 2 (TIMI grade flow 2/3). All balloon angioplasties were performed during continuous administration of nitrates. There was no significant difference with relation to lesion diameter, lesion stenosis, or diameter of the left circumflex coronary artery between the acute and chronic phase in both groups. The distal diameter, however, was smaller during the acute phase than in the chronic phase in both groups (1.7 +/- 0.5 vs 2.0 +/- 0.4 mm, p < 0.001; 2.0 +/- 0.4 vs 2.2 +/- 0.3 mm, p < 0.05, respectively). The percent vasoconstrictive response of the distal segment was greater in the primary PTCA group than in the elective PTCA group (11.2 +/- 18.1 vs -1.9 +/- 7.1%, p < 0.0001, respectively). In conclusion, nitrate-resistant coronary artery vasoconstriction following primary PTCA occurs distal to the site of balloon dilation.

Aged↗