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Biomedical subjects

E Suzuki

Publications and source records attributed to E Suzuki.

At least 271 records · Page 15Linked to original sources

Immunolocalization of a Drosophila phosphatidylinositol transfer protein (rdgB) in normal and rdgA mutant photoreceptor cells with special reference to the subrhabdomeric cisternae.

Distribution of rdgB protein, which was recently shown to be a Drosophila phosphatidylinositol transfer protein, was studied in the photoreceptor cells of compound eyes of normal and rdgAPC47 mutant of Drosophila melanogaster by immunoelectron microscopy using (1) pre-embedding HRP staining, (2) pre-embedding NANOGOLD labeling followed by siliver enhancement, (3) and post-embedding colloidal gold labeling methods. In normal cells, immunoreactivity was localized to the membranes of subrhabdomeric cisternae (SRC) and adjacent plasma membranes at the bases of photoreceptive microvilli. In rdgAPC47 mutant cells, whose SRC gradually degenerate, the immunoreactivity in the plasma membranes at the bases of microvilli disappeared in parallel with the degeneration of SRC. Instead, the abnormally proliferated membranous structures became labeled by the antibody. These results indicate that the rdgB protein is normally localized to the SRC membranes and probably adjacent photoreceptive membranes, suggesting the involvement of the rdgB protein in the phosphatidylinositol transfer between SRC and photoreceptive membranes.

Animals↗

[Sarcoidosis].

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Diagnosis, Differential↗

Does endothelin work as an intrarenal mechanism to alter pressure natriuresis in spontaneously hypertensive rats?

OBJECTIVE: To study the possible involvement of intrarenal endothelial dysfunction in the modulation of the pressure-natriuresis curve in spontaneously hypertensive rats (SHR). METHODS: We examined the effect of endothelin on pressure natriuresis in isolated perfused kidneys from 16-week-old SHR and Wistar-Kyoto (WKY) rats. Plasma and urinary endothelin levels in intact rats and the rate of endothelin release from isolated kidneys were also determined. RESULTS: Urinary sodium excretion by SHR kidneys was 60% less than by WKY rat kidneys at a given perfusion pressure. Endothelin-1 increased the renal vascular resistance dose-dependently and the change was comparable in SHR and WKY rats. A high perfusate concentration of endothelin-1 markedly reduced urinary sodium excretion, resulting in a significant rightwards shift of the pressure-natriuresis curve. However, endothelin-1 at concentrations below 0.1 nmol/l did not decrease urinary sodium excretion, despite its renal vasoconstrictory activity. In a different in vivo study, plasma endothelin-like immunoreactivity was similar in the two groups, as was the urinary endothelin excretion. However, the rate of endothelin release from isolated SHR kidneys was slightly greater than from WKY rat kidneys. CONCLUSION: Since the difference in endothelin levels is not remarkable, it seems unlikely that increased intrarenal production of endothelin plays a role in the maintenance of hypertension in SHR by modulating the pressure-natriuresis curve.

Animals↗

[Correlation between clinical stages on chest X-ray and findings in transbronchial lung biopsy specimens of sarcoidosis patients].

The 565 pulmonary tissue specimens taken from 155 sarcoidosis patients by transbronchial lung biopsy (TBLB) were studied by light microscopy. In stage II and III patients, the number of granulomas, the positive rate of hyalinofibrous granuloma, the relative proportion of hyalonofibrous granuloma group, and the degree of perigranulomal fibrosis and granuloma confluence were significantly higher than those in stage 0 and I patients. In stage I patients, the resolution of bilateral hiller lymphadenopathy was significantly more frequent in the atrophic granuloma group than in the hyalinofibrous granuloma group. The pulmonary lesions had a tendency to persist for a long time in stage II and III patients with hyalinofibrous granuloma or granuloma confluence. Newly appearing pulmonary lesions showed hypertrophic granulomas, as well as, marked lymphocytic cuffing. It appears that the changes in the stage on chest X-ray relate, not to the number of granulomas, but to the morphological findings of granulomas.

Biopsy↗

Mechanisms underlying the augmented responses of deoxycorticosterone acetate-salt hypertensive rats to neutral endopeptidase inhibitors.

OBJECTIVE: To explore the mechanisms for augmented neutral endopeptidase inhibitor-induced natriuresis in deoxycorticosterone acetate (DOCA)-salt rats. METHODS: We examined effects of a neutral endopeptidase-inhibitor, candoxatril, on plasma and urinary brain natriuretic peptide (BNP) levels, the influence of a specific atrial natriuretic peptide (ANP) receptor antagonist, HS-142-1, on the response to candoxatril, and the renal neutral endopeptidase activity in DOCA-salt rats. RESULTS: Candoxatril decreased blood pressure and increased urinary sodium excretion, both of which were greater in DOCA-salt rats than in normotensive control rats. These effects were associated with a significant rise in the plasma BNP level and the plasma ANP level in DOCA-salt rats. Urinary ANP excretion also increased, but urinary BNP excretion was not changed by candoxatril. Pretreatment with a specific ANP receptor antagonist (HS-142-1) diminished the effect of candoxatril on urinary sodium excretion, blood pressure and urinary cyclic GMP excretion. Urinary neutral endopeptidase-like activity was greater in DOCA-salt rats than in control rats. Northern blot analysis revealed that the ratio of renal neutral endopeptidase messenger RNA (mRNA) to beta-actin mRNA was comparable between the two groups. CONCLUSIONS: The neutral endopeptide inhibitor exerted its hypotensive and natriuretic effects mainly via the potentiation of the endogenous natriuretic peptides, including BNP. The augmented response of DOCA-salt rats also seems to be mediated by both the downregulation of clearance receptors and an increase in renal neutral endopeptidase activity.

Animals↗

[Pharmacokinetics of carboplatin in a patient under hemodialysis].

A patient with ovarian cancer under long-term hemodialysis was treated with carboplatin at 240 mg/m2 via intravenous drip infusion for 30 min. Hemodialysis was performed 1 or 2 hrs after the administration of carboplatin. The pharmacokinetics of carboplatin were determined, plasma total and free carboplatin-derived platinum (total Pt and free Pt) levels declined rapidly in the former. The AUC, T1/2 and Cmax of total and free Pt were estimated to be 7.14 and 3.14 mg/ml x min, 35.1 and 18.2 h, and 15.1 and 10.0 micrograms/ml, respectively. Plasma total and free Pt levels showed the same as normal control in the latter. The AUC, T1/2 and Cmax of total and free Pt were estimated to be 8.70 and 5.09 mg/ml x min, 27.6 and 21.9 h, and 13.2 and 13.2 micrograms/ml, respectively. No severe side effect was observed after administration of carboplatin. In conclusion, carboplatin may be given to the patient 2 hrs before hemodialysis in view of the pharmacokinetics.

Carboplatin↗

[Prognosis of interstitial pneumonitis (IP) in polymyositis (PM)/dermatomyositis (DM)].

IP, the major complication of PM/DM, is closely related to the life of these patients. In this study the course and prognosis of IP associated with PM/DM were investigated. Thirty IP patients with PM/DM were divided into 4 groups according to the course of IP. Clinical manifestations, laboratory data, chest radiographs and treatment were examined retrospectively. Eleven cases improved (Group I), 11 cases were exacerbated (Group E), 3 cases were unchanged (Group U), 2 cases died due to rapid progression of IP (Group D) and 3 cases dropped out. Both Group D patients were middle aged female DM patients without CPK elevation. All cases were treated with corticosteroids. The clinical manifestations, laboratory data, chest radiographs and initial dose of corticosteroid were not markedly different between Group I and E. The total dose of corticosteroids during the first 3 months tended to be higher in Group I than in Group E. Unlike idiopathic interstitial pneumonitis, the decrease in lung volume on chest radiographs improved after the treatment in 5 cases. We conclude that IP associated with PM/DM should be treated initially with high doses of corticosteroids.

Adult↗

Blood levels of leukotrienes (LTC4, D4, E4, B4) in asthmatic patients during attack and remission.

To assess the contribution of the leukotrienes, LTC4, D4, E4 and B4 during bronchial asthma attacks, simultaneous determination was made of their levels in venous blood. 25 patients with bronchial asthma (15 atopic types, 10 non-atopic types) participated in this study and 4 normal controls were used. Samples were obtained using heparinized syringe from the patients before treatment. A radioimmunoassay was conducted to measure LTs after purification with a Sep-pak column and separation by HPLC. In normal subjects, the levels were less than the minimal detectable amounts. LTC4, D4, E4 and B4 during asthmatic attacks were 100 +/- 179, 88 +/- 116, 479 +/- 291, and 55 +/- 73 (Mean +/- SD) pg/ml respectively (n = 27). Peptide LTs in remission were below minimal detectable levels. LTD4 in patients with moderate attacks was significantly (p < 0.05) higher than in those with mild attacks. Peptide LTs in moderate attack exceeded those in mild attacks, although not to a statistically significant degree. No significant differences in LT during attacks could be detected in atopic or non-atopic type patients. LTs would thus appear importantly involved in asthmatic attacks in atopic and non-atopic type patients, although other chemical mediators may give rise to airway inflammation.

Adolescent↗

Studies on the antiviral activity of propagermanium with immunostimulating action.

The effects of propagermanium (3-oxygermylpropionic acid polymer) on various virus-infected mice were investigated. Propagermanium did not inhibit the multiplication of various DNA or RNA viruses in vitro. Oral administration of propagermanium in mice infected with herpes simplex virus type I (HSV-1) significantly prolonged the mean survival days. The efficacy of propagermanium at doses of 1 and 10 mg/kg daily was 13.4 +/- 2.3 and 14.2 +/- 2.3 mean survival days in comparison with 7.7 +/- 0.5 mean survival days at control group. In vaccinia virus-infected mice, oral doses of propagermanium ranging from 0.2 to 10 mg/kg suppressed the number of pocks on the tail which induced by the virus. Propagermanium (0.5-10 mg/kg) orally given to HSV-1-infected mice induced cytotoxic T lymphocytes (CTL) against HSV-1 antigen. In addition, propagermanium (1-10 mg/kg) enhanced interferon-gamma (IFN-gamma) induction in mice treated with Mycobacterium bovis (BCG). In mice spleen cells cultured with Concanavalin A, 0.1 to 10 micrograms/ml of propagermanium stimulated interleukin 2 (IL-2) production. It seems likely that the antiviral activity of propagermanium was exerted via enhancement of host immune resistance against viral infection.

Adjuvants, Immunologic↗

Assay of enzymic O-methylation of catechol oestrogens by high-performance liquid chromatography with coulometric detection.

A simple and sensitive method for the determination of guaiaicol oestrogens enzymatically formed from 2- or 4-hydroxyoestradiol, by means of high-performance liquid chromatography with coulometric detection, has been developed. Catechol and guaiacol oestrogens were efficiently separated on a reversed-phase column, using 0.5% ammonium phosphate buffer (pH 3.0)-acetonitrile (59:41, v/v) as the mobile phase, and detected coulometrically in a screening-oxidation mode at +0.10 V and +0.35 V, respectively. The method was applied to the assay of in vitro enzymic O-methylation of catechol oestrogens. After 2- or 4-hydroxyoestradiol had been incubated with rat red blood cells in the presence of S-adenosylmethionine, the resulting guaiacols and unchanged substrate were percolated through an Extrelut-3 cartridge. The dried eluate was redissolved and directly injected. This simple procedure was as sensitive as the previously reported method using gas chromatography-mass spectrometry in a selected ion monitoring mode.

Animals↗

Evidence for C-type natriuretic peptide production in the rat kidney.

To elucidate the physiological role of C-type natriuretic peptide (CNP) as a local mediator, we examined the production of CNP in the rat kidney. The content of CNP in the kidney was 0.47 +/- 0.02 [SE] fmol/mg wet weight and the major molecular form of CNP was CNP-53. An established cell line from the rat kidney, NRK-52E cell, secreted CNP at a rate of 9.15 +/- 0.96 fmol/24 hr/mg protein. Furthermore, CNP mRNA was detected in the rat kidney and NRK-52E cell utilizing reverse transcription-polymerase chain reaction (RT-PCR). On the other hand, ANP in the rat kidney (2.56 +/- 0.19 fmol/mg wet weight) had the molecular form of alpha-ANP, but ANP mRNA was not detected by RT-PCR. No BNP immunoreactivity was found in the rat kidney, although BNP mRNA was detected by RT-PCR. These results indicate that only CNP among the natriuretic peptides is produced in significant amounts in the rat kidney under normal physiological conditions and that renal parenchymal cells may produce CNP.

Amino Acid Sequence↗

Absence of nonpercutaneous transmission of hepatitis C virus in a colony of chimpanzees.

Transmission of hepatitis C virus (HCV) was studied in a colony of 85 chimpanzees using assays for anti-HCV and HCV-RNA. Thirteen of the 85 sera were positive for anti-HCV, and 12 of the 13 were also positive for HCV-RNA. All of the anti-HCV positive sera except one were obtained from chimpanzees which had been inoculated with non-A, non-B hepatitis virus. On the other hand, only one of 63 sera of chimpanzees without history of experimental infection of the virus was positive for anti-HCV. Transmission to this chimpanzee was thought to be a needle contaminated with HCV. All 39 samples of chimpanzees born in the center were negative for both anti-HCV and HCV-RNA. Sixteen of their mothers had undergone experimental infection, and 6 of them were positive for both anti-HCV and HCV-RNA. These results suggest that nonpercutaneous transmission, including sexual and mother-to-infant transmissions, is not an important mode of transmission. If these findings apply to humans, definition of inapparent sources of the infection is needed.

Animals↗

Structural analysis of oxidation products of urofuran acid by hypochlorous acid.

The oxidation of urofuran acid derivatives (1-2) by hypochlorous acid (HOCl) was investigated with the goal to possibly simplify the detection of their metabolites in biological materials. The oxidation products of 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (1) were obtained as an isomeric mixture and confirmed to exist as cis (3a) and trans (3b) isomers, based on their 13C nuclear magnetic resonance (NMR) spectra. Similarly, the products of 5-H substituted acid 2 obtained by oxidation with HOCl were identified as 4a and 4b by 13C and 1H NMR which indicated the presence of cis and trans hemiacetal hydrogens at C-5 in a ratio of 2.11:1. The oxidation was found to proceed in a manner different from that of the F-acid, because of the presence of the electron withdrawing COOCH3 group at C-3 which favored the nucleophilic attack on the carbonyl group to afford cis- and trans-2,5-dihydroxy-2,5-dihydrofurans (3a-b, 4a-b).

Chromatography, Gel↗

Enzymatic O-methylation of catechol estrogens in red blood cells: differences in animal species and strains.

Enzymatic O-methylation of catechol estrogens in red blood cells has been investigated with respect to species difference. In the presence of S-adenosylmethionine, 2- or 4-hydroxyestradiol (2-OHE2 or 4-OHE2) was incubated with blood lysate obtained from rats (five strains), guinea pigs, mice, rabbits, dogs, monkeys, and humans, respectively. The yielded guaiacols and unchanged substrate were determined by gas chromatography/mass spectrometry in a selected ion monitoring mode employing the corresponding 2H4-labeled compounds as internal standards. The total amounts of guaiacols formed from 2-OHE2 and 4-OHE2 were different, being the highest (79.6% and 38.1%) in monkeys and the lowest (5.1% and 1.9%) in humans. The ratios of isomeric guaiacols formed from 4-OHE2 (4Me/3Me) were 7.6-71, while those from 2-OHE2 (2Me/3Me) were 1.4-3.2. Thus, marked differences in O-methylation of catechol estrogens were observed among animal species, but no significant strain difference was detected in rats.

Adult↗

Distribution of mec regulator genes in methicillin-resistant Staphylococcus clinical strains.

The distributions of the mec regulator genes mecI and mecR1, which were identified on the chromosome of mecA-carrying Staphylococcus aureus N315, in methicillin-resistant staphylococci isolated in Japan and various countries were studied. Screening by dot blot hybridization by using polymerase chain reaction (PCR)-amplified probes revealed that at least the 5'-end region of the mecR1 gene was present in all strains tested, whereas about 40% of the strains were negative for the mecI gene. The data suggested that these regulator genes were the original components of the additional mec region DNA of methicillin-resistant S. aureus as well as methicillin-resistant, coagulase-negative staphylococci of seven staphylococcal species (S. epidermidis, S. haemolyticus, S. hominis, S. sciuri, S. capitis, S. caprae, and S. warneri). The mecI gene, which presumably codes for the repressor protein of the mecA gene, was found to harbor a point mutation in all six mecI-positive methicillin-resistant S. aureus strains, and their basal level of mecA gene transcription was elevated compared with that of strain N315, which harbors a presumably intact counterpart of the mecI gene. The data suggested that the mecI gene encodes for a strong repressor function on mecA gene transcription and is deleted or mutated in clinical methicillin-resistant S. aureus strains with high levels of resistance to methicillin.

Amino Acid Sequence↗

Mechanisms for altered endothelium-dependent vasorelaxation in isolated kidneys from experimental hypertensive rats.

To study mechanisms for attenuated endothelium-dependent vasorelaxation in hypertension, we examined the effects of acetylcholine (ACh) on renal vascular resistance (RVR) and release rates of endothelium-derived relaxing factor (EDRF) in kidneys isolated from spontaneously hypertensive rats (SHR), deoxycorticosterone acetate (DOCA) salt-hypertensive (DOCA salt) rats, and Dahl salt-sensitive (Dahl S) rats. Decreases in RVR by ACh were smaller in hypertensive rats than in their normotensive controls. The release rate of nitric oxide into the perfusate, which was estimated using nitrite-nitrate as an index, did not differ between SHR and Wistar-Kyoto rats (WKY). However, the release rate of EDRF was markedly decreased in both DOCA salt rats and Dahl S rats compared with their normotensive controls (10(-7) M ACh: DOCA salt 45 +/- 6 vs. control 410 +/- 60 pmol.min-1.g-1 kidney wt, P < 0.001). In SHR, high-K+ perfusion or pretreatment with glibenclamide, inhibitors of endothelium-derived hyperpolarizing factor (EDHF), significantly reduced ACh-induced vasorelaxation only in WKY, resulting in no differences in the RVR reduction between SHR and WKY. Thus attenuated ACh-induced vasorelaxation in the SHR kidney may be attributed to a decrease in EDHF, but to a decrease in EDRF in DOCA salt rats and Dahl S rats.

Acetylcholine↗

Role of endogenous atrial natriuretic peptide in DOCA-salt hypertensive rats. Effects of a novel nonpeptide antagonist for atrial natriuretic peptide receptor.

BACKGROUND: To explore roles of endogenous atrial natriuretic peptide (ANP) in blood pressure and volume regulation, we examined the effects of a newly developed ANP antagonist, HS-142-1 (HS) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. METHODS AND RESULTS: We examined 1) the effects of HS on ANP- or brain natriuretic peptide (BNP)-induced reductions in renal vascular resistance (RVR) of rat isolated perfused kidneys, 2) the effects of HS on cyclic GMP (cGMP) production in rat cultured vascular smooth muscle cells pretreated with ANP or BNP, and 3) the renal and systemic effects of HS in DOCA-salt-treated rats and control rats. We found that 1) HS dose-dependently reversed ANP- or BNP-induced decreases in RVR; 2) ANP or BNP at 100 nM caused an eightfold increase in cGMP production. These increases in cGMP were inhibited by HS in a dose-dependent fashion, and 300 micrograms/ml HS decreased cGMP to the control level. HS alone did not influence RVR or cGMP production; and 3) DOCA-salt rats showed higher plasma concentrations of ANP (198 versus 75 pg/ml) and BNP (23.7 versus 2.7 pg/ml, each p < 0.01) than the control rats. Bolus administration of 8 mg/kg HS elevated blood pressure by 8% (p < 0.01). This rise in blood pressure was attributed to an increase in systemic vascular resistance (+14%, p < 0.05). Conversely, urinary excretion of sodium (-41%), glomerular filtration rate (-27%), and plasma (-77%) and urinary cGMP (-69%, each p < 0.01) were decreased by administration of 8 mg/kg HS. These effects were dose dependent in DOCA-salt rats but slight or negligible in the control rats. CONCLUSIONS: These results suggest that endogenous ANP and BNP may be involved in the regulation of blood pressure and body fluid volume in DOCA-salt rats in which ANP and BNP secretion is augmented.

Animals↗