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Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

At least 19 recordsLinked to original sources

Health-related quality-of-life after external beam radiation therapy for localized prostate cancer: intensity-modulated radiation therapy versus conformal radiation therapy.

We compared health-related quality-of-life (HRQL) after intensity-modulated radiotherapy (IMRT) with statuses obtained after old and new protocols of three-dimensional conformal radiation therapy (3DCRT) for localized prostate cancer. We measured the general and disease specific HRQL using the MOS 36-Item Health Survey (SF-36), and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI), respectively. IMRT resulted in similar profiles of general and disease-specific HRQL to two other methods within the first year after treatment. Moreover, IMRT gave rise to comparable urinary, intestinal and sexual side effects despite the high dose of radiation applied.

Aged↗

Isolated osteochondroma near the mandibular angle.

A benign tumour of osseous and cartilaginous origins, osteochondroma generally develops in osseous tissue and is frequently found near the end of long bones. It is relatively rare in the oral and maxillofacial region but is common in the mandibular condyle and coronoid process in the pediculate form. This is a report on a rare case of osteochondroma in soft tissue near the mandibular angle without pedicle to the bone.

Adult↗

Development of a micro-planar amperometric bile acid biosensor for urinalysis.

The determination of bile acid concentration in urine is useful for the screening and diagnosis of various hepatobiliary diseases. Currently, there is no concise method to determine bile acid concentration in urine. This study describes a bile acid biosensor fabricated by electrochemical technique for urinalysis. The micro-planar electrodes employed for the study consisted of a working electrode (platinum), a counter electrode (platinum) and a reference electrode (silver/silver chloride (Ag/AgCl)). The sensor chip was coated with Nafion using a spin-coater in order to both eliminate many interference species in urine and achieve long-term stability of the reference electrode. Nafion coating allowed the sensor chip to prevent the electrode reaction from interference species in urine, because it is charged negative strongly (Nafion contains sulfonic acid group). Three enzymes (bile acid sulfate sulfatase: BSS, beta-hydroxysteroid dehydrogenase: beta-HSD, and NADH oxidase: NHO) were immobilized by glutaraldehyde (GA: cross-linker) onto the sensor chip, because the immobilization of enzymes by GA is simple and commonly carried out. The sensor chip was able to detect bile acid in buffer solution. The optimum enzyme ratio immobilized onto the sensor chip was BSS:beta-HSD:NHO=4:4:20 U/1 chip. There was a relationship between the concentration of bile acid and the response current value. The dynamic range of the sensor chip was 2-100 microM for bile acid. Additionally, bile acid in the urine specimen could be detected using this bile acid biosensor. We present a simple and rapid bile acid biosensor with high sensitivity and high reproducibility.

Bile Acids and Salts↗

Antidepressant-like activity of a Kampo (Japanese herbal) medicine, Koso-san (Xiang-Su-San), and its mode of action via the hypothalamic-pituitary-adrenal axis.

Koso-san (Xiang-Su-San in Chinese), a Kampo (Japanese herbal) medicine, is used clinically in East Asia for the treatment of depression-like symptoms associated with the initial stage of the common cold, allergic urticaria due to food ingestion, irritable bowel syndrome, chronic fatigue syndrome, insomnia, and autonomic imbalance. However, the antidepressant-like activity of Koso-san has never been evaluated scientifically. In this study, ddY mice subjected to a combination of forced swimming and chronic mild stresses were termed depression-like model mice. The degree of the depression-like state was measured by the animal's duration of immobility using the forced swimming test (FST). Oral administration of Koso-san (1.0 g/kg/body wt./day, 9 days) significantly shortened the duration of immobility of the depression-like model mice in the FST; however, locomotor activity was not affected. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays an important role in the pathophysiology of depression. Levels of corticotropin-releasing hormone mRNA expression in the hypothalamus and proopiomelanocortin mRNA expression in the pituitary were significantly increased, and glucocorticoid receptor protein expression in the hypothalamus paraventricular nucleus was downregulated in the depression-like model mice. However, Koso-san ameliorated these alterations to the normal conditions. The results of this study suggest that Koso-san shows the antidepressant-like effect through suppressing the hyperactivity of the HPA axis in depression-like model mice.

Animals↗

The effect of ephedrine and phenylephrine on BIS values during propofol anaesthesia.

BACKGROUND: The purpose of this study was to evaluate the effect of ephedrine and phenylephrine on propofol concentrations and bispectral index during propofol anesthesia. METHODS: General anaesthesia was induced with propofol and was maintained with propofol (4 mg kg-1 h-1) and fentanyl. Vecuronium was used to facilitate the artificial ventilation of the lungs. Patients with systolic blood pressure > 90 mmHg were defined as the control group (n = 16). Patients who had to be treated for larger decreases in arterial blood pressure (systolic blood pressure 60, whereas no patient in the control or phenylephrine groups had bispectral index >60. There were no significant differences in propofol concentrations or cardiac output relative to baseline at 3 or 10 min after the administration of ephedrine or phenylephrine. CONCLUSIONS: Ephedrine increases bispectral index values without decreasing propofol concentrations during general anesthesia.

Anesthesia, Intravenous↗

Male New Zealand Black/KN mice: a novel model for autoimmune-induced permanent alopecia?

BACKGROUND: Irreversible, permanent and scarring alopecia is associated with several autoimmune diseases, including all autoimmune connective tissue disorders. The pathogenesis of autoimmune-induced permanent alopecia (APA) is still poorly understood, and instructive, simple mouse models for the study of APA are needed urgently. During the course of our studies in a well-established mouse model for chronic rheumatoid arthritis, the New Zealand Black/KN (NZB/KN) mouse, we noticed that ageing male NZB/KN mice developed spontaneous APA. OBJECTIVES: To study whether alopecia seen in ageing male NZB/KN mice displays key features of human APA and may, thus, be a useful new mouse model for clinically relevant APA research. METHODS: NZB/KN, the F1 hybrid of NZW/N Slc x NZB/KN (W/BKN F1), the F1 hybrid of NZB/KN x NZW/N Slc (BKN/W F1), and the F2 hybrid of W/BKN F1 x W/BKN F1 mice were employed in this study, in order to check which strain carries the highest risk of alopecia development. Besides routine histology, CD3, CD4 and CD8 expression as well as immunoglobulin (Ig) G and IgM deposition in hair follicles were investigated by immunohistology/immunofluorescence. Mast cell distribution/degranulation and Ki-67 (proliferation)/TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling) (apoptosis) positive cells were also analysed. RESULTS: Only F2 male NZB/KN mice were prone to develop alopecia, suggesting that Y chromosome-associated gene(s) are involved in the pathogenesis of APA, which incidence rises with increasing age. The lesional alopecia skin in 12-month-old male NZB/KN mice showed a sharp decline in hair follicle density, thus meeting a key criterion of permanent alopecia. Both macroscopically and histologically, the alopecia seen in these mice resembled in many respects different stages of clinical APA, such as alopecia associated with chronic discoid lupus erythematosus (DLE) in humans. Lesional APA hair follicles in mice displayed intrafollicular and perifollicular mononuclear cell infiltrates, as well as an increased number of activated (degranulated) perifollicular mast cells. In the fully developed lesion, many CD4+ cells were seen in perifollicular locations, including the epithelial stem cell region (bulge), and also contained a few CD8+ T cells. IgM deposits were found in the follicular basement membrane zone (BMZ). Both in the bulge and the hair matrix region of the affected anagen hair follicles, there were signs of massive keratinocyte apoptosis. CONCLUSIONS: Our currently available data suggest that male but not female NZB/KN mice may indeed represent a suitable mouse model for APA, with some similarities to the permanent alopecia seen in human DLE patients, although additional and confirmatory investigations are needed before this mouse strain can be accepted as a murine equivalent of APA in humans.

Aging↗

[Posterior ventricular septal perforation successfully repaired through right ventricular approach].

A 65-year-old man underwent a successful repair of a posterior ventricular septal perforation (VSP) 9 days after suffering an acute inferior myocardial infarction. After hospitalization, his hemodynamic condition gradually worsened, in spite of administering intensive medical therapy. Emergent operation was performed on the 4th day after onset. An equine pericardial patch was sutured around the VSP through the right ventricular side of the septum using the double-patch repair method and the right ventricular wall was closed as using the standard extracorporeal perfusion technique. The dimensions of the VSP measured 5 mm in diameter. Transesophageal echocardiography was performed on the 14th postoperative day. Cardiac catheter examination was done on the 18th postoperative day. No residual shunt was recognized and cardiac function was good. He was discharged on the 20th postoperative day. The occurrence of a posterior VSP is comparatively rare, and repair of VSP is difficult to perform during an acute period. Therefore, the operative results of VSP cases remain poor.

Aged↗

Structure formation in a binary monolayer of dipolar particles.

We propose an experimental technique for an easy to control realization of a binary dipolar monolayer where the two components have oppositely oriented dipole moments constrained perpendicular to the plane of motion without the application of an external field. The experimental setup ensures that hydrodynamic effects do not play a crucial role in the structure formation, the particles move deterministically due to the dipole-dipole interaction. At low concentrations, cluster-cluster aggregation occurs with chainlike morphologies, while at high concentration the particles self-assemble into various types of binary crystal lattices, in good agreement with the theoretical predictions. The structures formed by the particles are found to be sensitive to external perturbations due to the central interparticle forces, however, static friction arising at the contact surface of particles can increase the stability compared to systems with only viscous friction.

Journal Article↗

Solvent dependence of the spectra and kinetics of excited-state charge transfer in three (alkylamino)benzonitriles.

Steady-state absorption and emission spectra and emission decay kinetics are reported for 4-aminobenzonitrile (ABN), 4-(1-azetidinyl)benzonitrile (P4C), 4-(1-pyrrolidinyl)benzonitrile (P5C), and 4-(1-piperidinyl)benzonitrile (P6C) in 24 room temperature solvents. In solvents of modest to high polarity, P4C, P5C, and P6C exhibit dual fluorescence and emission decays characteristic of the transformation from an initially prepared (LE) state to a more polar charge transfer (CT) state, whereas ABN does not undergo this reaction. The frequencies of the steady-state absorption and emission spectra of all of these solutes can be rationalized using a dielectric continuum description of the solvent and considering only the minima on the reactive surfaces, which are assumed to involve both an intramolecular (twisting) and a solvation coordinate. Characteristics of the gas-phase solutes deduced from this analysis are in good agreement with electronic structure calculations and indicate that differences in their spectra mainly reflect differences in the relative energies of the gas-phase LE and CT states. The relative yields of LE and CT emission are not described as satisfactorily by this model, and reasons for this failure are discussed. The kinetics of the LE --> CT reaction vary considerably with solute and solvent. In many solvents, the emission decays of P4C are reasonably described by a simple two-state kinetic scheme with time-independent rate constants. In P5C and P6C multiexponential decays are observed that reflect time-dependent shifts of the component spectra as well as time-dependent reaction rates. A simplified analysis of these complex dynamics provides estimates for both the free energy change Delta(r)G and (average) LE --> CT rate constant k(f) for a wide range of solute and solvent combinations. The driving force for reaction (-Delta(r)G) follows the order P6C > P5C > P4C and increases with increasing solvent polarity. The reaction rates are correlated to Delta(r)G and follow the opposite trend. The relationships observed between k(f) and Delta(r)G suggest that static solvent effects, i.e., barrier height changes, are the primary determinants of the solvent dependence in P4C. Correlations between barrier-corrected rates and solvation times suggest that dynamical solvent effects contribute substantially to the solvent dependence of the rates in P5C, and especially P6C.

Journal Article↗

Interferon-gamma is a potent inducer of catagen-like changes in cultured human anagen hair follicles.

BACKGROUND: Interferon (IFN)-gamma appears to be an important hair cycle modulator in mice. It is unclear whether it has similar hair growth modulatory functions in human hair follicles. OBJECTIVES: To study whether IFN-gamma can be exploited to modulate the growth, pigmentation and/or cycling of organ-cultured human anagen scalp hair follicles, as an in vitro indicator system for how IFN-gamma affects human hair growth in vivo. This was correlated with the hair follicle expression patterns of IFN-gamma receptors alpha and beta. In addition, we wanted to establish a new, simple tool for the rapid experimental induction of catagen in vitro. METHODS: Normal human scalp hair follicles in the anagen VI stage of the hair cycle were cultured according to the method of Philpott et al., with or without IFN-gamma (50-1000 IU mL(-1)). Hair shaft elongation and pigmentation changes were measured, complemented by quantitative histomorphometry to assess changes in hair follicle cycling (hair cycle score), proliferation (Ki-67), melanogenesis (Masson-Fontana) and apoptosis (TUNEL). IFN-gamma receptors were also localized by immunofluorescence and EnVision technique. As transforming growth factor (TGF)-beta2 is a recognized key inducer of catagen in human hair follicles, TGF-beta2 expression was investigated by tyramide signal amplification and reverse transcription-polymerase chain reaction in anagen hair follicles treated with vehicle (phosphate-buffered saline) or IFN-gamma. RESULTS: IFN-gamma rapidly inhibited hair elongation in cultured human anagen hair follicles and induced morphological signs of catagen transformation after only 4 days of culture, i.e. faster than with other reported catagen-inducers (e.g. TGF-beta2). Proliferation was inhibited, apoptosis was increased and follicular melanogenesis was switched off in hair bulb keratinocytes treated in situ with IFN-gamma. Anagen hair follicles displayed strong IFN-gamma receptor alpha-like immunoreactivity, while the immunoreactivity for IFN-gamma receptor beta in the hair matrix was only weak. TGF-beta2 immunoreactivity and mRNA transcript levels were enhanced in hair follicles treated with IFN-gamma. CONCLUSIONS: These data suggest that IFN-gamma is a potent catagen inducer in normal human scalp hair follicles, which express cognate receptors, and show that IFN-gamma administration offers an excellent tool for experimental catagen induction in organ-cultured human hair follicles. This catagen induction probably occurs at least in part via upregulation of the recognized catagen-stimulatory growth factor TGF-beta2.

Apoptosis↗

Quantitative analysis of the effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetyltriglycine in dogs.

Effect of probenecid on pharmacokinetics of 99mTc-mercaptoacetylytriglycine (99mTc-MAG3) in dogs was investigated before (control), and after 15 min and 24 h of i.v. injection of probenecid (20 mg/kg). Plasma concentration-time profiles of 99mTc-MAG3 were described with a two-compartment open model. Plasma 99mTc-MAG3 clearances (Clp, ml/min/kg) were 7.9 +/- 0.5, 3.3 +/- 0.5 and 4.8 +/- 1.3 in control, 15 min and 24 h after probenecid administration respectively. Similarly, the biological half-lives at elimination phase (t(1/2), h) were 0.61 +/- 0.09, 0.79 +/- 0.11 and 0.74 +/- 0.12, and volumes of distribution at steady state (Vdss, L/kg) were 0.29 +/- 0.04, 0.20 +/- 0.05 and 0.25 +/- 0.06 respectively. The prolonged biological half-life and decreased Vdss decreased Clp significantly. Clp was a function of plasma probenecid concentration based on Michaelis-Menten kinetics. The maximum Clp inhibition (Imax) by probenecid and the plasma probenecid concentration that induced 50% of Imax (I50) were estimated to be 72 +/- 12% and 13 +/- 8 microg/ml respectively. This means that the rest (about 28%) of the Clp is not blocked by probenecid alone, suggesting the possibility of another route(s) of elimination or renal transporters which are independent from probenecid. Moreover, inter-species correlation between Clp of 99mTc-MAG3 and body weight are discussed.

Animals↗

Enhanced expression of suppressor of cytokine signalling-1 in the liver of chronic hepatitis C: possible involvement in resistance to interferon therapy.

Interferon-alpha (IFN-alpha) is widely used in the treatment of chronic hepatitis C (CHC). The suppressor of cytokine signalling (SOCS) family has been implicated in the regulation of JAK-STAT signalling, including IFN signalling. The negative effect of SOCS expression on the response of CHC to IFN-alpha is demonstrated here. The transcriptional levels of SOCS-1 and -3 in the livers of 21 patients with CHC and eight controls were investigated by quantitative reverse transcription-polymerase chain reaction. We established stable transfectants of SOCS-1 in a human hepatoma cell line, PLC/PRF/5 and analysed the effects of SOCS-1 on the phosphorylation of IFN-alpha-induced STAT-1 tyrosine by immunoblotting and the expression of antiviral genes by Northern blot. A prospective cohort study on SOCS-1 expression and clinical outcome was carried out in 77 patients with CHC who received IFN therapy. SOCS-1, but not SOCS-3, transcripts in the livers of CHC were significantly higher than controls (P < 0.005). IFN-alpha-induced STAT-1 phosphorylation and the expression of antiviral genes were inhibited in SOCS-1-transfected cells. Patients showing high SOCS-1 expression in the liver had a significantly lower rate of sustained virological response (SVR) to IFN therapy than those with low SOCS-1 expression (P = 0.0014). A multivariate analysis performed with host factors revealed that SOCS-1 staining in the liver can serve as a significant predictor for IFN SVR (P = 0.004). SOCS-1 expression is enhanced in the livers of CHC patients and might be involved in resistance to IFN therapy.

Adult↗

Effects of dioxin and nutrition on cellular proliferation and dioxin- and estrogen-linked genes in ovarian cancer cell lines.

This study was undertaken to examine the effects of dioxin (TCDD) and nutrition on cellular proliferation and dioxin- and estrogen-linked gene expression in ovarian cancer cell lines. Caov-3 and SK-OV-3 cells were incubated in a medium supplemented with 0.5-10% fetal bovine serum (FBS). Cell proliferation was assayed with an MTT assay. Dioxin- and estrogen-linked genes (AhR, ERalpha, ERbeta, CYP1A1 and ARNT) expressed were determined with the RT-PCR method. Caov-3 cells, but not SK-OV-3 cells, were proliferated with TCDD alone with increased AhR and ERa mRNA expressions when incubated in the low FBS concentration. CYP1A1 and ARNT mRNA expressions of SK-OV-3, but not that of Caov-3, were suppressed in the low FBS (under 1.0%) concentration. In the low FBS concentration medium with dioxin, AhR and ERa expression were increased with the proliferation of Caov-3 cells; CYP1A1 and ARNT were stable. Each ovarian cancer cell line may have its own distinct responsiveness to dioxin depending on the nutritional state.

Cell Line, Tumor↗

Sinorhizobium meliloti RpoH1 is required for effective nitrogen-fixing symbiosis with alfalfa.

Sinorhizobium meliloti is a root-nodulating, nitrogen-fixing bacterium. An S. meliloti strain that is mutant for the rpoH(1) gene, which encodes a sigma(32)-like protein, elicits the formation of ineffective nodules on the host plant alfalfa. We characterized the rpoH(1) mutant for phenotypes related to symbiosis. Alfalfa nodules formed by the rpoH(1) mutant exhibited greatly reduced levels of acetylene reduction activity compared to the wild-type nodules. Whereas intracellular colonization by rhizobia was observed in a zone just below the apical meristem, we found ultrastructural abnormalities and signs of degeneration of bacteroids within many host cells in the proximally adjacent zone. In the proximal part of the nodule, only a few nodule cells contained bacteroids. In contrast, the rpoH(1) mutant showed normal induction of nitrogen fixation gene expression in microaerobic culture. These results suggest that the rpoH(1) mutation causes early senescence of bacteroids during the endosymbiotic process, but does not affect the invasion process or the synthesis of the nitrogenase machinery. The rpoH(1) mutant exhibited increased sensitivity to various agents and to acid pH, suggesting that RpoH(1) is required to protect the bacterial cell against environmental stresses encountered within the host. Since RpoH(1) was previously reported to be required for the synthesis of some heat shock proteins (Hsps), we examined the transcription of several genes for Hsp homologs. We found that transcription of groESL(5), lon, and clpB after heat shock was RpoH(1)-dependent, and conserved nucleotide sequences were found in the -35 and -10 regions upstream of the transcription start sites of these genes. Although groESL(5) expression is almost completely dependent on RpoH(1), we found that a groESL(5) mutant strain is still capable of normal symbiotic nitrogen fixation on alfalfa.

Base Sequence↗

Clinical implications of insulin-like growth factors through the presence of their binding proteins and receptors expressed in gynecological cancers.

Since insulin-like growth factors (IGFs) are known to play critical roles in the development of cancers, we examined the expression of the mRNA and protein of IGF-binding protein (IGFBP) and cognate receptors to assess their possible involvement in gynecological malignancy. The specimens were obtained from 46 endometrial, 32 cervical, and 20 ovarian cancers, and 28 normal endometrium. In endometrial cancers, IGFBP-1, -2, -3 and IGF-1 receptor (IGF-1R) mRNAs were detected in 8.7, 89.1, 95.6, and 91.3% of tumors, respectively, and the corresponding proteins in 54.3, 54.3, 95.6, and 91.3% of tumors, respectively. Clinical staging was significantly related to the expression of IGFBP-1 and -2 proteins. In ovarian cancers, their mRNAs were detected in 10.0, 90.0, 95.0, and 100.0%, and proteins in 15.9, 50.0, 90.0, and 80.0%. In cervical cancers, their mRNAs were detected in 6.3, 90.6, 96.8, and 87.5%, and proteins in 44.4, 18.8, 84.4, and 87.5%. IGF-1R was highly expressed in all specimens. The abnormally balanced co-expression of IGFBPs and high levels of IGF-R in gynecological cancers suggest that IGF signals might be involved in the growth of these tumors.

Adenocarcinoma↗

Differences in ethoxyquin nephrotoxicity between male and female F344 rats.

Dose-response studies have shown a sharp threshold for the renal papillary toxic effect in male rats between 0.25% and 0.5% ethoxyquin (Eto) in the diet over 6 months. Although similar elevated urinary protein (albumin) levels resulted from dietary Eto (0.5%) in both males and females, papillary necrosis was male specific. Following [14C]Eto administration, radiolabel was associated with urinary albumin but not alpha 2 globulin (alpha(2mu)-g). Autoradiographic studies indicated that the sex differences in nephrotoxicity do not involve differences in distribution or retention of Eto. Faecal and urinary metabolic profiles were also similar in the two sexes. The sharp threshold of toxicity in the male rat could indicate a fine balance between toxifying/detoxifying metabolism of Eto.

Administration, Oral↗