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Biomedical subjects

S Naito

Publications and source records attributed to S Naito.

At least 127 records · Page 7Linked to original sources

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗

Expression of recombinant human zona pellucida protein 2 and its binding capacity to spermatozoa.

The human zona pellucida (ZP) is composed of three major glycoproteins: ZP1, ZP2, and ZP3. The aim of this study was to clarify the role of ZP2 by focusing on the polypeptide structure. We produced in Escherichia coli a recombinant human ZP2 protein (rec-hZP2) corresponding to amino acid sequence 1-206 of the mature protein. The final yield of rec-hZP2 protein was 80 microg/ml Luria Broth medium. After 2-h incubation of human spermatozoa with rec-hZP2 in vitro, an immunofluorescent study indicated that rec-hZP2 bound only to acrosome-reacted spermatozoa. The binding site migrated from the acrosome to the midpiece of the spermatozoa. Rabbit and mouse antisera produced against rec-hZP2 stained native human ZP in the immunofluorescent study, and significantly blocked human sperm binding and penetration into human ZP as compared to control values. The N-terminal polypeptide portion of human ZP2 was shown to contain a binding site for acrosome-reacted spermatozoa and to play an important role in secondary sperm binding and penetration into the ZP.

Acrosome↗

Temporal and spatial patterns of accumulation of the transcript of Myo-inositol-1-phosphate synthase and phytin-containing particles during seed development in rice.

Myo-inositol-1-phosphate (I[1]P) synthase (EC 5.5.1.4) catalyzes the reaction from glucose 6-phosphate to I(1)P, the first step of myo-inositol biosynthesis. Among the metabolites of I(1)P is inositol hexakisphosphate, which forms a mixed salt called phytin or phytate, a storage form of phosphate and cations in seeds. We have isolated a rice (Oryza sativa L.) cDNA clone, pRINO1, that is highly homologous to the I(1)P synthase from yeast and plants. Northern analysis of total RNA showed that the transcript accumulated to high levels in embryos but was undetectable in shoots, roots, and flowers. In situ hybridization of developing seeds showed that the transcript first appeared in the apical region of globular-stage embryos 2 d after anthesis (DAA). Strong signals were detected in the scutellum and aleurone layer after 4 DAA. The level of the transcript in these cells increased until 7 DAA, after which time it gradually decreased. Phytin-containing particles called globoids appeared 4 DAA in the scutellum and aleurone layer, coinciding with the localization of the RINO1 transcript. The temporal and spatial patterns of accumulation of the RINO1 transcript and globoids suggest that I(1)P synthase directs phytin biosynthesis in rice seeds.

Amino Acid Sequence↗

Crystallization of lipopolysaccharide from a Salmonella typhimurium semi-rough (SR) mutant.

Salmonella typhimurium SR-form lipopolysaccharide (LPS), consisting of a single repeating unit of the O-antigenic polysaccharide, linked to the R-core consisting of oligosaccharide that is, in turn, linked to lipid A, formed crystals whose shapes were hexagonal plates, discoids, and solid columns when precipitated by the addition of 2 volumes of 95% ethanol containing 375 mM MgCl2 and kept in 70% ethanol containing 250 mm MgCl2 at 4 C for 10 days. Among these crystals, the basic form is considered to be the hexagonal plates. Analyses of hexagonal plate crystals showed that they consist of hexagonal lattices with a lattice constant (a axis) of 4.62 A and longitudinal axis (c axis) of approximately 100 A. In X-ray diffraction patterns in the low-angle region, crystals of S. typhimurium SR-form LPS exhibited much less distinct reflections when compared with crystals of synthetic Escherichia coli-type lipid A. In contrast to the previous finding that S. minnesota S-form LPS possessing the O-antigenic polysaccharide does not crystallize under the same experimental conditions as used in the present study, the presence of a single repeating unit of the O-antigenic polysaccharide does not inhibit crystallization.

Carbohydrate Conformation↗

Left posteroseptal Mahaim fiber associated with marked longitudinal dissociation.

We report a patient who underwent radiofrequency catheter ablation of a left posteroseptal atrioventricular (AV) Mahaim fiber with a marked longitudinal dissociation. During atrial pacing, Wenckebach-type atrioventricular block over the accessory pathway was observed with progressive preexcitation and no change in polarity of the delta waves. The AV conduction curve was discontinuous, with a distinct "jump-up" in local AV conduction time of 84 ms. The earliest ventricular activation was recorded from the posteroseptal portion of the mitral annulus, and the unipolar electrogram from a distal electrode had a high, steep deflection with uniphasic QS-like activity with 62 ms of local AV conduction time.

Adult↗

Antigen-specific, IgE-selective unresponsiveness induced by antigen-liposome conjugates. Comparison of four different conjugation methods for the coupling of antigen to liposome.

BACKGROUND: We have previously reported that ovalbumin (OVA) coupled with liposome via glutaraldehyde (GA) induced OVA-specific- and IgE-selective unresponsiveness in mice. METHODS: In this study, OVA-liposome conjugates were made using four different coupling protocols: via GA, N-(6-maleimidocaproyloxy) succinimide (EMCS), disuccinimidyl suberate (DSS) and N-succimidyl-3(2-pyridyldithio)propionate (SPDP) and the induction of antigen-specific IgG and IgE antibody production was investigated for each. In addition, antigen-specific cytokine production by spleen cells of mice immunized either with OVA-liposome or with OVA adsorbed with aluminum hydroxide was investigated. RESULTS: OVA-liposome conjugates coupled via GA or DSS did not induce anti-OVA IgE antibody production but induced substantial anti-OVA IgG antibody production. On the other hand, the induction of anti-OVA IgE unresponsiveness by OVA-liposome conjugates coupled via EMCS or SPDP was incomplete. The amount of interleukin 4 (IL-4) produced by spleen cells stimulated in vitro with OVA correlated well with anti-OVA IgE antibody production in donor mice. However, the production of no other cytokine, i.e., IL-2, IL-5, IL-10 or interferon-gamma, was correlated with in vivo IgE antibody production. CONCLUSION: OVA-liposome coupled via GA or DSS induced complete suppression of anti-OVA IgE production. The results in this study further suggest that the regulation of IgE antibody production does not necessarily correlate with so-called Th1 cytokine production.

Animals↗

Genotypic evolution in a quinolone-resistant Neisseria gonorrhoeae isolate from a patient with clinical failure of levofloxacin treatment.

Recently, a reduction in the antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to newer fluoroquinolones including levofloxacin in vitro has been recognized in Japan. We examined the quinolone resistance mechanisms in N. gonorrhoeae isolates from a patient with clinical failure of levofloxacin treatment. Man with gonococcal urethritis was treated with oral 100 mg levofloxacin 3 times daily for 7 days. However, clinical failure of the treatment was observed. The minimum inhibitory concentration of levofloxacin for the posttreatment isolate (4.0 microg/ml) was 4-fold higher than that for the pretreatment isolate (1.0 microg/ml). To analyze quinolone resistance mechanisms in the set of isolates, we performed DNA sequencing of the quinolone resistance-determining regions within the gyrA and parC genes. Moreover, we assayed the intracellular levofloxacin and norfloxacin accumulation level in these isolates. The pretreatment isolate contained three substitutions compared to susceptible wild-type isolate, including serine to phenylalanine at position 91 and aspartic acid to asparagine at position 95 in the GyrA protein, and serine to proline at position 88 in the ParC protein. The posttreatment isolate had four substitutions, including the same three substitutions and an additional glutamic acid to glutamine substitution at position 91 in ParC. There was no significant difference in the level of accumulation of levofloxacin and norfloxacin between the pretreatment and posttreatment isolates. Our results indicate that levofloxacin selects a mutant having an additional alteration within the gene cording for the ParC protein during treatment, which may have enhanced quinolone resistance in the organism.

Adult↗

Clinical and morphometrical interrelationships in patients with overt nephropathy induced by non-insulin-dependent diabetes mellitus. A light- and electron-microscopy study.

To clarify the relationships between clinical and renal structural findings in non-insulin-dependent diabetes mellitus (NIDDM), we studied 19 renal biopsy specimens from patients with overt diabetic nephropathy induced by NIDDM. By a conventional biopsy examination using light, immunofluorescent and electron microscopy, we excluded patients with any non-diabetic renal diseases which may have caused urinary abnormalities. Using standard stereological methods, the glomerular filtration surface area per nephron (S-Filt/neph), mesangial volume per glomerulus (V-Mes/glom), mesangial matrix volume per glomerulus (V-MM/glom) and the width of the glomerular basement membrane (GBM) were measured in nonoccluded glomeruli. The hyaline change in the arteriole was analyzed semiquantitatively using light microscopy as an index of arteriolar hyalinosis. Light-microscopic findings demonstrated minimal lesions in 4 cases, focal and/or segmental sclerotic lesions in 4 cases, and diffuse mesangial expansion in 11 cases (with and without nodular lesions in 9 and 2 cases, respectively). Mean glomerular volume of an open glomerulus in diabetic patients was 1.6 times the reference value obtained from nondiabetic patients with mild proteinuria and/or hematuria and normal renal function. Clinical parameters, including the duration of diabetes, urinary protein excretion and creatinine clearance were all related to S-Filt/neph, V-Mes/glom, V-MM/glom and the width of the GBM. In addition, V-MM/glom, the width of the GBM and the index of arteriolar hyalinosis were closely interrelated. Based on these findings, diabetic renal changes, including an increase in the mesangial matrix, thickening of the GBM and arteriolar hyalinosis, appeared to progress in parallel, and may reflect various clinical manifestations in patients with overt diabetic nephropathy induced by NIDDM without nondiabetic renal lesions.

Adult↗

Association between HLA-DRB1*15 and Japanese patients with rheumatoid arthritis complicated by renal involvement.

We performed serological phenotyping of HLA antigens in 175 patients with rheumatoid arthritis (RA) with (n = 41) and without (n = 134) renal involvement (RI), and DNA typing of HLA class II alleles in 75 patients. Among the patients with RA, the frequency of serologically determined HLA-DR4 was found to be significantly increased (odds ratio: 1.8, confidence interval: 1.3-2.5, p = 2.4x10(-4)). In the patients without RI, the frequency of serological DR4 significantly increased (odds ratio: 2.2, confidence interval: 1.6-3.3, p = 2. 6x10(-5)). On the other hand, among the patients with RI, a serological determinant, DR15, did significantly increase (odds ratio: 2.7, confidence interval: 0.9-8.4, p = 1.2x10(-3)) in comparison to the controls. At the DNA level, we found that the association of Japanese RA patients with serological HLA-DR4 was based on that with a genotype of HLA-DRB1*0405 (odds ratio: 2.4, confidence interval: 1.5-4.0, p = 4.4x10(-4)) and also found an association of HLA-DRB1*1501 (odds ratio: 2.8, confidence interval: 1.2-6.6, p = 0.017) with RA patients having RI. Our results confirmed the association of HLA-DRB1*04 with RA over the ethnic barrier at the DNA level. Our results also suggested a distinct genetic effect of HLA-DRB1*1501 in the aspect of the susceptibility of RI in RA.

Aged↗

Pharmacokinetics of BOF-4272, a xanthine oxidase inhibitor, after single intravenous or oral administration to male mice and rats.

BOF-4272, (+/-)-8-(3-methoxy-4-phenylsulphinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4 (1H)-one), is a new drug intended for the treatment of hyperuricaemia. This report describes the detailed pharmacokinetics of BOF-4272 in mice and rats after intravenous or oral administration. Plasma concentrations of BOF-4272 at 2-8h after intravenous administration were significantly higher in mice than in rats. Plasma concentrations of BOF-4272 after oral administration were significantly higher in fed mice than in fasted mice, but were similar in fasted and fed rats. The elimination half-life of the distribution phase (t1/2(alpha)) was similar in mice (0.158 h) and rats (0.210 h). The elimination half-life of the terminal elimination phase (t1/2(beta)) in mice was 1.936 h, while that in rats was 0.742 h. The volume of the central compartment (V1) was almost the same in mice (415 mL kg(-1)) and rats (440 mL kg(-1)). However, the volume of the peripheral compartment (V2) in mice was 1068 mL kg(-1), while that in rats was 92 mL kg(-1). The steady-state volume of distribution (Vss) was 2.8 times larger in mice than in rats. The area under the plasma concentration-time curve (AUC) in mice was 5332 ng h mL(-1), while that in rats was 3806 ng h mL(-1). The AUC0-24 h after oral administration was 2.5 times greater in fed mice than in fasted mice, and was 1.4 times greater in fasted rats than in fed rats. The correlation coefficients of Cmax and AUC0-24 h in both mice and rats after oral administration were greater than 0.997 in the dose range 1 - 125 mg kg(-1), indicating that the linear range of absorption or elimination (or both) of BOF-4272 is very wide. The results of the present study demonstrate that the mouse is a suitable animal species for evaluating the clinical pharmacokinetics of BOF-4272.

Administration, Oral↗

Metabolic pathways and pharmacokinetics of BOF-4272, a sulfoxide-containing drug, in the dog: in vivo and in vitro studies.

BOF-4272, (+/-)-8-(3-methoxy-4- phenylsulfinylphenyl)pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one, is a new drug intended for the treatment of hyperuricemia. This report describes the detailed metabolic pathways of BOF-4272 in the dog. The metabolic pathways were investigated using the metabolites found in plasma, urine, and feces after intravenous or oral administration of BOF-4272, as well as the metabolites found in the liver S9 incubation mixture after the addition of BOF-4272 or BOF-4269. BOF-4269 (the sulfide metabolite of BOF-4272) was the only metabolite detected in plasma and feces after the intravenous or oral administration of BOF-4272. BOF-4269 was detected in dog plasma after a lag time following the oral administration of BOF-4272, and the Cmax and AUC0-t of BOF-4269 were higher in fed dogs than in fasted dogs after the oral administration of BOF-4272. A small amount of BOF-4269 was detected in dog plasma immediately after the intravenous administration of BOF-4272. Only BOF-4276 (the sulfone metabolite of BOF-4272) was detected in the S9 incubation mixture after the addition of BOF-4272. Mainly BOF-4272 was detected and small amounts of BOF-4276 and M-1 (the hydroxy metabolite of BOF-4269) were detected in the S9 incubation mixture after the addition of BOF-4269. These findings suggest that BOF-4272 is mainly metabolized to BOF-4269 by the intestinal flora in dogs, whereas little of this drug is metabolized to BOF-4269 in the dog liver. In conclusion, this work has allowed us to formulate the proposed metabolic pathways of BOF-4272 in the dog.

Animals↗

[The application of the endotoxin test for globulin and other blood products].

The application of the endotoxin test for globulin and other blood products were investigated by two different limulus amebocyte lysate (LAL) test methods, colorimetric and kinetic turbidimetric methods, using two endotoxin-specific reagents. By the dilution of the blood products in 40 times or more, spiked endotoxin in the products was recovered accurately showing neither inhibition nor enhancement. The definite difference was not shown between the results obtained by the two LAL test methods. According to the method of the endotoxin test described under General Tests of The Japanese Pharmacopeia (thirteenth edition), JPXIII, the maximum valid dilution (MVD) for these products will be calculated to be 40 or more, so it is capable to measure the endotoxin limit for each product. This study indicates that the endotoxin test is applicable to measure the endotoxin content in globulin and other blood products as an alternative method for the rabbit pyrogen test.

Colorimetry↗

Quantitative analysis of surface P-wave morphology in isthmus ablation for type 1 atrial flutter: differentiation between complete isthmus block and slow isthmus conduction.

Changes in P-wave morphology in inferior leads during atrial pacing at the margins of the carvo-tricuspid isthmus have been reported to be useful for predicting the creation of isthmus block in radiofrequency (RF) ablation of type I atrial flutter (AFL). However, it is not known whether these changes in P-wave morphology allow the clinician to differentiate between complete isthmus block and slow isthmus conduction. P-wave morphology during low lateral right atrial (LLRA) pacing, as well as during coronary sinus ostium (PCS) pacing, was evaluated prior to ablation, during slow isthmus conduction, and after complete isthmus block in 30 patients with AFL. Changes in P-wave morphology during LLRA pacing were not sufficient to differentiate between complete isthmus block and slow isthmus conduction. While changes in P-wave morphology in lead II from inverted to biphasic during PCS pacing were observed in both slow isthmus conduction and complete isthmus block, the ratio of the positive component to the total P-wave amplitude (P-wave ratio) was significantly different between slow isthmus conduction (20+/-17%) and complete isthmus block (40+/-11%) (P<0.0001). When the P-wave ratio in lead II during PCS pacing was more than 75% of the F-wave ratio in lead II during AFL, bilateral complete isthmus block was predicted with a sensitivity of 88%, a specificity of 71%, a positive predictive value of 75%, and a negative predictive value of 85%. These results indicate that a P-wave ratio greater than 20% or a P-wave ratio during PCS pacing greater than 75% of the F-wave ratio during AFL may predict a bidirectional complete isthmus block.

Aged↗

Right ventricular infarction with cardiogenic shock treated with percutaneous cardiopulmonary support: a case report.

A patient with a right ventricular infarction was resuscitated with percutaneous cardiopulmonary support (PCPS), after attempts at reperfusion, high-dose inotropic support and intra-aortic balloon counterpulsation failed to improve the hemodynamic compromise. Emergency PCPS improved the cardiogenic shock and the reduced right ventricular load, allowing the ischemic right ventricle to recover in the setting of unsuccessful reperfusion. This case demonstrates the use of PCPS as a hemodynamic support device for spontaneous recovery of the ischemic right ventricle. PCPS may be a potential therapy for patients with right ventricular infarction.

Angioplasty, Balloon, Coronary↗

[Chlamydia trachomatis infection in male infertility--the clinical usefulness of the detection of antibodies against Chlamydia trachomatis].

BACKGROUND: The objective of this study is to investigate the clinical usefulness of the detection of antibodies against Chlamydia trachomatis (C. trachomatis) in potential male infertility patients. PATIENTS AND METHODS: Analysis of serum samples for the presence of antibodies against C. trachomatis by enzyme immunoassay was performed in 83 male infertility patients. RESULTS: Immunoglobulin A (IgA) and G (IgG)-antibodies against C. trachomatis were found in 16 and 10 of 83 serum samples (19.3 and 12.0%) respectively. IgA and/or IgG-antibodies against C. trachomatis were found in 20 of 83 serum samples (24.1%). Serum IgA, IgG, or IgA and/or IgG positive patients showed increased semen and urine leukocytes numbers and reduced semen volume and sperm numbers, compared with negative patients, respectively, although these effects are not statistically significant. By Spearman's correlation analysis, however, significant positive correlations with serum IgA or IgG antibody index were found in semen and urine leukocytes numbers. Significant negative correlations with serum IgA antibody index was found in semen volume. In serum IgA positive patients, only 1 of 8 first-voided urine samples was positive for C. trachomatis-DNA by PCR. Moreover, the positive rates of surum IgA antibody and cervical antigen in the 8 female partners of IgA positive patients were only 25% (2 of 8 serum samples) and 12.5% (1 of 8 cervical specimens) respectively. CONCLUSION: There was a high prevalence (24.1%) of serum IgA and/or IgG-antibodies against C. trachomatis from infertility patients. The existance of antibodies against C. trachomatis in serum samples possibly influence semen quality, suggesting that C. trachomatis infection may play an important role in male infertility.

Adult↗