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The present study aimed to establish candidate biomarker genes for the early detection of nephrotoxicity in mice, with a particular focus on nephrotoxicity caused by polyene macrolides. Comprehensive gene expression changes were evaluated using microarrays in a mouse model in which acute nephrotoxicity was induced by amphotericin B deoxycholate, trade name Fungizone. The upregulated genes identified through microarray analysis of kidney tissue of Fungizone-treated mice included several genes that have been reported as nephrotoxicity biomarkers in rats, and 14 genes were selected as candidate nephrotoxicity biomarkers. The usefulness of these genes as nephrotoxicity biomarkers in mice was evaluated further through expression profiling under several experimental conditions using real time RT-PCR. Expression of genes encoding kidney injury molecule 1, lipocalin 2, tissue inhibitor of metalloproteinase 1, and secreted phosphoprotein 1 was highly upregulated by Fungizone, nystatin, natamycin, amphotericin B methyl ester, and liposomal amphotericin B, and their area under the ROC curve values were more than 0.95. These genes were more sensitive at detecting nephrotoxicity than traditional clinical chemistry and histopathology parameters. This study provides novel evidence that these nephrotoxicity biomarker genes identified are translatable to mice, and that they are useful for early and sensitive detection of nephrotoxicity.

Background Although osteoarthritis (OA) is a highly prevalent joint disease, to date, no reliable biomarkers have been found for the disease. In this study, we attempted to identify factors the amounts of which significantly change in association with the progression of knee OA. Methods A total of 68 subjects with primary knee OA were enrolled in the study. These subjects were followed up over an 18-month period, and plasma and serum samples were obtained together with knee radiographs every 6 months, i.e., 0, 6, 12 and 18 months after the enrollment. Progressors and non-progressors were determined from the changes on radiographs, and plasma samples from those subjects were subjected to N-glycoproteomic 2D-LC-MALDI analysis. MS peaks were identified, and intensities for respective peaks were compared between the progressors and non-progressors to find the peak intensities of which differed significantly between the two groups of subjects. Proteins represented by the chosen peaks were identified by MS/MS analysis. Expression of the identified proteins was evaluated in synovial tissues from 10 OA knee joints by in situ hybridization, western blotting analysis and ELISA. Results Among the subjects involved in the study, 3 subjects were determined to be progressors, and 6 plasma and serum samples from these subjects were subjected to the analysis together with another 6 samples from the non-progressors. More than 3000 MS peaks were identified by N-glycoproteomic 2D-LC-MALDI analysis. Among them, 4 peaks were found to have significantly different peak intensities between the progressors and non-progressors. MS/MS analysis revealed that these peaks represented clusterin, hemopexin, alpha-1 acid glycoprotein-2, and macrophage stimulating protein, respectively. The expression of these genes in OA synovium was confirmed by in situ hybridization, and for clusterin and hemopexin, by western blotting analysis and ELISA as well. Conclusions In this study, 4 potential biomarkers were identified as potential prognostic markers for knee OA through N-glycoproteomic analysis. To the best of our knowledge, this is the first report for the use of glycoproteomic technology in exploring potential biomarkers for knee OA.

Objectives: The taste receptor gene family T2R has been implicated in the sensation of bitter taste. Phantogeusia is a spontaneous abnormal taste with no external stimulus. We analyzed the expression of T2R taste receptor genes in the tongues of patients with phantogeusia to assess their role in the pathogenesis of phantogeusia. Methods: We obtained specimens from 43 patients with phantogeusia and 24 normal volunteers by scraping the foliate papillae and examined these specimens for the expression of 10 T2R taste receptor genes using reverse transcription–polymerase chain reaction and electrophoresis. Results: The expression rate (subjects with detectable expression) of the 10 taste receptor genes in the healthy subjects ranged from 16.7% to 100%; 3 receptor genes were found in 50% or fewer of these subjects. In the patients with phantogeusia, the expression rate was increased significantly compared to that in the healthy control subjects for 3 of the 10 receptor genes examined. Conclusions: Our results show that the expression rate of some of the T2R taste receptor genes was increased significantly in patients with phantogeusia. These results suggest that increased expression of taste receptor genes is involved in the pathogenesis of phantogeusia; this finding may contribute to elucidation of the mechanism of this disorder.

A long-term study was carried out on 57 patients treated with radiation alone who had T2N0M0 squamous cell carcinoma of the glottic larynx. The response and survival rates were satisfactory, but the complete response (CR) and the larynx preservation rates showed a need for improvement. Thirty-four patients underwent salvage operations and a safe margin for the partial laryngectomy was evaluated by histopathological examination of serial sections of the surgical specimen.Although the effectiveness of combined chemoradiation therapy in the treatment of head and neck cancer has been reported, the facts remain unclear. The purpose of this study was to analyze the long-term outcomes of radiation therapy alone for T2N0M0 squamous cell carcinoma of the glottic larynx, i.e. the survival rate, the larynx preservation rate, and the reality of salvage operations. This is expected to contribute to an understanding of the synergistic effects of anticancer drugs used in combined chemoradiation therapy, the use of which will be expanded in the future. The reason for this is that the radiation source, radiation field, and radiation dose are nearly identical for patients with T2N0M0 squamous cell carcinoma of the glottic larynx.The subjects were 57 patients with untreated T2N0M0 squamous cell carcinoma of the glottic larynx. There were 55 males and 2 females. Their ages ranged from 31 to 86 years. The 4 MV Liniac X-ray external beam radiation therapy was carried out via two-dimensional horizontal opposing ports, 2 Gy per dose, five times a week with a total of 66 Gy.In 57 patients, we observed CR in 33 patients, partial response (PR) in 20 patients, no change (NC) in 4 patients, and progression disease (PD) in none of the patients. The response rate was 93.0% and the CR rate was 57.9%. The survival rates (Kaplan-Meier method) were: 5-year survival rate of 88.5% and 10-year survival rate of 73.5%. The larynx preservation rates (Kaplan-Meier method) were: 5-year larynx preservation rate of 60.4% and 10-year larynx preservation rate of 50.1%. The main side effect of grade 3 or more was only stomatitis in four patients, all of which were reversible changes (CTCAT v3.0 JCOG/JSCO). Salvage operation was required in 34 (59.6%) of 57 patients, 10 patients underwent partial laryngectomy, total laryngectomy was performed in 3 of the 10 patients following the partial laryngectomy, and 27 patients (47.4%) underwent total laryngectomy. The surgical specimens were serially sectioned at a thickness of 4 μm and examined histopathologically and compared to the macroscopic findings at surgery. The safe margin for partial laryngectomy was considered grossly to be 5 mm from the edge of the tumor.

We treated two patients with nasal tuberculosis. One was a 58-year-old female who visited our clinic because of right nasal obstruction and bleeding. Mild swelling of the inferior turbinate and a bloody nasal discharge were observed. Mycobacterium tuberculosis was cultured from the nasal discharge. Biopsy of the mucous membrane of the inferior turbinate showed a granuloma with epithelioid cells. The other was a 59-year-old female who visited us with complaints of right nasal obstruction, purulent nasal discharge, and frontal headache. Granulation, bleeding and crust attachment were observed on the right concha nasalis inferior and the nasal septum. Mycobacterium tuberculosis was cultured from the nasal discharge. Both patients had strongly positive Mantoux tests. Chest X-ray films showed evidence of old tuberulosis but no active pulmonary tuberculosis. Both patients were treated mainly with streptomycin and other anti-tuberculous drugs with satisfactory results.

An immunohistochemical investigation was conducted on infiltrating lymphocytes in submandibular glands removed from three cases with unspecific chronic sclerosing sialadenitis of the submandibular gland (unspecific CSSS) which has been described for the first time by Küttner. A high degree of lymphocyte infiltration was recognized and formation of lymphatic follicles was observed. In particular, activated B cells were predominantly observed in that part of the lymphatic follicles which was equivalent to germinal centers. In the T cell subset, the helper/inducer T cells displayed significant dominance over suppressor/cytotoxic T cells, and were distributed in the dark peripheral zone of the follicles. The distribution pattern of these lymphocytes seemed to be similar to antigenically stimulated lymph nodes and it was recognized that the unspecific CSSS could be a site of exceedingly active local immune responses. The authors believe that these findings support the view that unspecific CSSS (Küttner tumor) is an immune disorder.

We expeienced a case of rapid bone absorption of the femoral neck. A 55-year-old female who had been treated with oral medications for nearly thirty years for schizophrenia, was injured in a fall. She complained of right coxalgia, but fracture of the femoral neck was not diagnosed by anteroposterior radiograph in the local orthopaedic clinic. The pain didn't improve and she visited our hospital 50 days after the injury. Radiographs showed abnormal bone absorption of the femoral neck. The authors consider that the rapid bone absorption in this case was partly due to the mental disorder.

The clinical results after arthroscopic synovectomy in 24 knees of 14 RA patients with chronic synovitis were reviewed. The follow-up period ranged from 2 to 55 months, with an average of 32 months. The operated knee joints were divided into early synovectomy (Larsen's grade 0, 1, 2) and late synovectomy (Larsen's grade 3, 4, 5). Compared with preoperative findings, pain and swelling was on the whole improved. In early synovectomy, pain and swelling was improved in 11 of 13 knees and the effect was expected to remain for 3 to 5 years. In comparison, in late synovectomy, pain and swelling was improved in 5 of 9 knees (56%) within 3 years after surgery, with none achieving a good result after more than 3 years. This procedure seems to be indicated in early grade patients and appears to provide significant time saving in late grade patients.

Objective: Examine changes in the expression of taste receptor genes in patients who had loss of taste and those who had phantogeusia.Method: The subjects of this study consisted of 51 patients with loss of bitter taste and 43 patients with phantogeusia. The control group consisted of 24 subjects. We took specimens by scraping their foliate papillae. T2R family and TAS2R family gene expression was detected using RT-PCR and electrophoresis.Results: The patients with loss of bitter taste showed a significant decrease in the frequency of expression of taste receptor genes T2R8 (P = .002), 10 (P = .001), 13 (P = .003), 16 (pTAS2R40 (p48 (P = .007) compared with the control group. The frequency of gene expression of TAS2R42 (P = .008) and T2R3 (P = .033) were significantly increased in patients with phantogeusia.Conclusion: Expression of some genes was decreased in patients with loss of taste, while expression of other genes was increased in patients with phantogeusia. It was suggested that conflicting changes...

Allergic rhinitis is the most common allergic disease, displaying the typical nasal symptom of congestion. Prostaglandin D(2) (PGD(2)), a chemical mediator released in large amounts by mast cells upon allergic stimulation in humans, is known to be involved in nasal congestion. However, the mechanism by which this congestion occurs remains unclear.The effect of PGD(2) on the nasal airflow in guinea pigs was measured using a noninvasive approach that avoided any anesthetic effect. Isometric tension of isolated nasal mucosa and the nasal vascular corrosion resin cast technique were used to clarify the area of nasal mucosal vessels affected by PGD(2), and to examine the mechanism of PGD(2)-induced nasal congestion. Moreover, the involvement of second messengers in PGD(2)-induced mucosal relaxation was investigated.PGD(2) induced an increase in intranasal pressure in a guinea pig model of rhinitis. Additionally, sinusoidal microvessel dilatation appeared around the septum using the vascular corrosion resin cast technique in the nasal mucosa. Moreover, relaxation of the nasal mucosa following stimulation of the prostanoid DP-1 receptor was associated with cAMP levels in the tissue.PGD(2)-induced nasal congestion is caused by direct dilatation of the sinusoid vessels through the increase of cAMP levels in the nasal mucosa, demonstrating that the mechanism of PGD(2)-induced nasal congestion is different from other chemical mediators. Consequently, antagonists for the prostanoid DP-1 receptor would be an alternative approach for the relief of nasal congestion. Alternatively, the combined administration with antagonists for other mediators involved in nasal congestion may also be a valuable therapy for allergic rhinitis.

Consecutive daily low-dose S-1 therapy was less toxic and its efficacy was not inferior to the conventional administration schedule. Consecutive daily low-dose S-1 chemotherapy appears to be a treatment option for patients in whom it is difficult to continue the conventional administration schedule of S-1 due to adverse events.To evaluate the safety and efficacy of consecutive daily low-dose S-1 therapy in an adjuvant setting.This study investigated 52 patients with absence of local residual tumor, lymph node metastasis or distant metastasis after radical treatment for advanced head and neck squamous cell carcinoma. After receiving informed consent from patients, half of the usual dose of S-1 was administered daily for 2 years. The safety, feasibility, and efficacy of this approach were evaluated.Hematologic toxicity was seen in 51 of 52 patients (98.1%), but grade 3 hematologic toxicity was found in only 2 patients (3.8%). Nonhematologic toxicity was observed in 15 patients (28.8%) and all were grade 1. Forty-three patients (82.7%) were able to complete the chemotherapy for 2 years without dose reduction. The 3-year disease-free survival rate and 3-year survival rate were 82.6% and 94.0%, respectively.

The aim of this work is to examine the clinical findings of patients with taste disorders due to central lesions and also to study the central gustatory pathway in humans. We conducted a retrospective review of 13 patients with central taste disorders that visited Nihon University Itabashi Hospital. An additional 25 cases with central taste disorders previously reported in the literature were assessed in the study. We examined 38 patients with taste disorders due to central lesions. The sites of the central lesions and their frequencies, the laterality of taste disorders relative to the central lesions, and prognosis of taste disorders were studied. We identified the following taste-related regions in the central nervous system: the medulla, pons, midbrain, thalamus, internal capsule, putamen, corona radiata, and cerebral cortex. As for the laterality of the taste disorders, we observed more ipsilateral cases for lesions located from the medulla to the pons. We observed ipsilateral, contralateral, and bilateral cases for lesions located above the midbrain, but bilateral cases were more frequently detected. Taste disorders of 80% of the patients improved by 24 weeks. The prognoses of central taste disorders appeared to be good. We identified eight central regions supposed to be relate to taste disorders. From the laterality of the taste disorders relative to the central lesions, it was suggested that the central gustatory pathway ascends ipsilaterally from the medulla to the pons, branches at the upper pons, and then ascends bilaterally from the midbrain to the cerebral cortex.

Using the projector-augmented plane wave method, we study diffusion and dissociation processes of C(2)H(2) molecules on the ferromagnetic bcc-Fe(110) surface and investigate the formation process of graphene created by C(2)H(2) molecules. The most stable site for C(2)H(2) on the Fe surface is a hollow site and its adsorption energy is - 3.5 eV. In order to study the diffusion process of the C(2)H(2) molecule, the barrier height energies for the C atom, C(2)-dimer and CH as well as the C(2)H(2) molecule are estimated using the nudged elastic band method. The barrier height energy for C(2)H(2) is 0.71 eV and this indicates that the C(2)H(2) diffuses easily on this FM bcc-Fe(110) surface. We further investigate the two step dissociation process of C(2)H(2) on Fe. The first step is the dissociation of C(2)H(2) into C(2)H and H, and the second step is that of C(2)H into C(2) and H. Their dissociation energies are 0.9 and 1.2 eV, respectively. These energies are relatively small compared to the dissociation energy 7.5 eV of C(2)H(2) into C(2)H and H in the vacuum. Thus, the Fe surface shows catalytic effects. We further investigate the initial formation process of graphene by increasing the coverage of C(2)H(2). The formation process of the benzene molecule on the FM bcc(110) surface is also discussed. We find that there exists a critical coverage of C(2)H(2) which characterizes the beginning of the formation of the graphene.

Nei's (1972) genetic distance were estimated among 21 populations of the common freshwater shrimp Paratya compressa improvisa, living in the northern part of Japan. The estimates were based on examination of 18 enzyme loci by starch-gel electrophoresis. These shrimp populations were genetically classified into three geographic groups on the basis of predominating alleles typical for two loci Fdp-1 and Fdp-2. The "Kanto group" consisted of individuals having Fdp-1a and Fdp-2c, the "Japan Sea group" having Fdp-1b and Fdp-2a, and the "Pacific Ocean group" having Fdp-1b and Fdp-2c. Nei's genetic distance among the three different geographic groups, varied from 0.0572 to 0.2136. Average genetic distances were 0.1001 between Pacific Ocean and Japan Sea groups, 0.0851 between Pacific Ocean and Kanto groups, and 0.1990 between Japan Sea and Kanto groups. These values of genetic distance among the three groups are comparable with those among different subspecies.

多胚性カンキツの受精胚組織を起源とする胚化カルス経由の体細胞胚, すなわち雑種クローンの獲得について検討した. カラタチの花粉を交配して78日後の‘マルチーズブラッド’オレンジの胚珠を供試し, マイクロマニピュレータ用ガラスピペットで珠孔近傍から少量の組織片を摘出した. BAとNAAを一定量含む Murashige & Tucker (1969) 培地で培養してカルスを誘導し, malt extract 400mg・l-1および adenine 10mg・l-1添加した同培地に継代すると胚様体が再生された. その後, 実生化をはかったところ, 一部の処理区で三出葉を有する実生が観察された. 三出葉を有する実生の獲得率が高かったのは, カルスを誘導する際にBA 5.0mg・l-1とNAA 0.1mg・l-1, またはBA 1.0mg・l-1とNAA 0.1mg・l-1を加えた場合であった. 優勢形質である三出葉を有する実生は, 受精胚組織が脱分化した後に胚化して再生したものとみられ, 本手法によって雑種クローン増殖の可能性が示唆された.

胚発生の初期段階にあるカンキツの幼胚珠を温度環境を変えて培養し, 交雑胚の獲得率について検討した. カラタチの花粉を交配した‘マルチーズブラッド’オレンジと‘ダンカン’グレープフルーツの幼胚珠を malt extract 400mg・l-1および adenine 10mg・l-1を添加した Murashige & Tucker (1969) 培地に置床した. 温度条件を変えて70日間培養したところ, 生存胚珠数は25℃区および30℃区で多く, 20℃区ではかなり減少する傾向であった. これらの胚珠を, malt extract の濃度を次第に下げ adenine の代わりにGA310mg・l-1を添加した同培地で継代培養した. 培養135日後に三出葉を有した雑種実生の獲得率を調査した結果,‘マルチーズブラッド’オレンジの場合に30℃区で13.5%,‘ダンカン’グレープフルーツの場合に30℃区で10.8%, 25℃区で, 1.1%であり, in vitro において高温条件を与えながら幼胚珠を培養すると雑種実生を効率的に獲得できることが明らかとなった.

While inhaled glucocorticoids are the best treatment for the majority of chronic asthmatics, there is a small group who do not respond to these drugs or whose disease can only be controlled by high doses of oral glucocorticoids with risks of severe side effects. Therefore, a safe novel anti-asthmatic agent which has a different mechanism from that of glucocorticoids is needed for the management of asthma. We have previously shown that an orally active prostanoid DP receptor antagonist, S-5751, had potent anti-inflammatory effects in guinea pig and sheep asthma models. In this study, using a rat asthma like model, we found that lung neutrophilia and proinflammatory cytokine secretion as well as bronchial hyperresponsiveness and lung eosinophilia were induced by repeated antigen-inhalations after antigen-sensitization. These symptoms are similar to the pathogenesis of symptomatic asthma. Orally-administered prostanoid DP receptor antagonists S-5751 and pinagladin significantly suppressed not only bronchial hyperresponsiveness and lung eosinophilia but also neutrophilia and mucus secretion in the lung, while oral prednisolone inhibited only bronchial hyperresponsiveness and eosinophil infiltration. In addition, prostanoid DP receptor antagonists significantly suppressed interleukin (IL)-1β, IL-6 and CXCL1 mRNA in contrast to suppression of IL-4 and CCL11 mRNA by prednisolone. The majority of prostanoid DP receptor-expressing cells in both rat and human asthmatic lungs are infiltrative macrophages and/or monocytes. These results suggest that prostanoid DP receptor antagonists utilize different mechanisms from glucocorticoids, and that they would be a novel alternative and/or combination drug for asthma therapy.

To predict the efficacy of cisplatin and radiation therapy for maxillary squamous cell carcinoma, we examined the mRNA expression of 14 cisplatin-resistant genes and p53 mutation in specimens biopsied from patients prior to initiation of therapy. Five of 10 patients had mutations in the p53 gene, of whom four had residual tumors pathologically following chemoradiotherapy (p=0.0476). Of 14 genes examined, the mRNA expression of ATP7B was significantly lower in cases that were resistant to chemoradiotherapy. Six genes including multidrug resistance protein 1 (MDR-1), multidrug resistance associated protein 1 (MRP-1), Cu++ transporting, beta polypeptide (ATP7B), xeroderma pigmentosum, complementation group A (XPA), excision repair cross-complementing rodent repair deficiency, complementation group 1 (ERCC-1) and B-cell CLL/lymphoma 2 (BCL2) were down-regulated in cases of recurrent cancers. These results show that the evaluation of p53 mutation provides the most useful predictor of therapeutic effects. In responder cases, the drug-resistant genes that were determined in cell lines by culture do not necessarily translate into clinical relevance.

It has been suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy. A large-scale genotyping analysis of gene-based single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes identified the gene encoding acetyl-coenzyme A carboxylase beta (ACACB) as a candidate for a susceptibility to diabetic nephropathy; the landmark SNP was found in the intron 18 of ACACB (rs2268388: intron 18 +4139 C > T, p = 1.4×10−6, odds ratio = 1.61, 95% confidence interval [CI]: 1.33–1.96). The association of this SNP with diabetic nephropathy was examined in 9 independent studies (4 from Japan including the original study, one Singaporean, one Korean, and two European) with type 2 diabetes. One case-control study involving European patients with type 1 diabetes was included. The frequency of the T allele for SNP rs2268388 was consistently higher among patients with type 2 diabetes and proteinuria. A meta-analysis revealed that rs2268388 was significantly associated with proteinuria in Japanese patients with type 2 diabetes (p = 5.35×10−8, odds ratio = 1.61, 95% Cl: 1.35–1.91). Rs2268388 was also associated with type 2 diabetes–associated end-stage renal disease (ESRD) in European Americans (p = 6×10−4, odds ratio = 1.61, 95% Cl: 1.22–2.13). Significant association was not detected between this SNP and nephropathy in those with type 1 diabetes. A subsequent in vitro functional analysis revealed that a 29-bp DNA fragment, including rs2268388, had significant enhancer activity in cultured human renal proximal tubular epithelial cells. Fragments corresponding to the disease susceptibility allele (T) had higher enhancer activity than those of the major allele. These results suggest that ACACB is a strong candidate for conferring susceptibility for proteinuria in patients with type 2 diabetes., Author Summary Although cumulative epidemiological findings have suggested that genetic susceptibility plays an important role in the pathogenesis of diabetic nephropathy, no gene conferring susceptibility to diabetic nephropathy has been definitively identified. In a large-scale association study of 1,312 Japanese subjects with type 2 diabetes using SNPs from a Japanese SNP database, we show that the T-allele of ACACB rs2268388 is associated with diabetic nephropathy. We also show that the association is consistently observed in patients with type 2 diabetes and proteinuria across different ethnic groups, including populations of European descent. Because a DNA fragment corresponding to the disease susceptibility allele is shown to have higher enhancer activity, we hypothesize that the increase in the expression and/or activity of the encoded acetyl-coenzyme A carboxylase beta contributes to the development and progression of diabetic nephropathy. Our present analysis provides novel insight into the pathogenesis of diabetic nephropathy. This finding is important because diabetic nephropathy is a leading cause of end-stage renal disease and affects life expectancy in subjects with type 2 diabetes.

The planum semilunatum is located on the lateral side of the crista ampullaris of thesemicircular canal. With regard to the functions of the planum semilunatum, some researchers assume the existence of secretory activity based on the microstructural features observed in isotopic experiments. In the present study, in order to confirm the existence of an immunological mechanism in the ampulla of the semicircular canal, the distribution of immunoglobulins in the semi-circular canal of guinea pigs was investigated immunohistochemically. Positivity of IgG wasobserved in the constituent cells of the planum semilunatum or beneath the basement membrane ofthe cells.It is concluded that ample IgG, which is an important constituent of the body fluids, is collected within this region. The planum semilunatum containing such ample amounts of IgG might be involved in the immunological mechanism operating in the ampullar of the semicircular canal.

We experienced methrtrexate (MTX) therapy at a low dose level of 1, 25-7.5mg/week in 10 refractory RA patients with an uncontrollable inflammatory process, and studied its indication and effects. Eight of these 10 patievds began to show an improved Lansbury index value about 4 weeks after the initiation of drug therapy. Among the components of the Lansbury index a definite improvement was noted in morning stiffness, srasping power and the joint score, while the erythrocyte sedimentation rata improved slightly. No efficacy side effects occsred in one of 10 patients with the elevation of the transaminase serum level. The results of this therapeutic trial with MTX indicate that a favorable response can be expected even at a low dose level of 2.5mg/week or below in those patients with refractory RA whose treatment by gold sodium thrimalate, auranofin, bucllamine, D-penicillamine and or steroids has not been effective.

In order to estimate the degree of genetic divergence between two Paratya subspecies, Paratya compressa compressa and P. c. improvisa, which are common freshwater shrimp in Japan, isozymic analysis was carried out by starch gel electorophoresis. Eighteen loci coding for 15 enzymes were scored in both subspecies. Of the 18 loci, 7 divergent loci with no common allele were observed between the two subspecies. Nei's genetic distance between the subspecies was 0.597. Average heterozygosity was 0.044 in P. c. compressa but 0.069 in P. c. improvisa, indicating a difference in genetic variability between the two subspecies. These results indicate that the two subspecies are genetically divergent. The number of divergent loci and genetic similarities pointed to useful in-dices for genetic divergence between closely related species in the process of speciation.

Of patients with RA of the elbow treated by synovectomy in our department, 10 (12 elbows) in whom postoperative follow-up observations were feasible, were evaluated for the results of the operative treatment. They consisted of 3 males (5 joints) and 7 females (7 joints) with a mean age of 63.2 years and a mean follow-up period of 4 years. The affected synovium was removed through a longitudinal skin incision laterally. During the follow-up period, we noted relief of pain, improvement of the ranges of elbow flexion and extension, forearm supination and pronation in almost all the patients. An improvement of ADL was also prominent with the restoration of the patients' abilities to comb their hair with their hands, to eat and to hold Something. The results of the operation were thus quite gratifying with a definite improvement achieved in the range of motion of the joint and also of ADL.

Mo2C was formed as a eutectic in the final stage of solidification of high Cr cast iron containing Mo. This finely dispersed carbide that is harder than Cr7C3 is expected to give good wear resistivity of hot rolls. The effect of addition of Mo up to 10 mass% in 3mass%C-20mass%Cr iron was investigated. With increasing Mo content, tensile strength and fracture toughness decreased monotonically, and hot wear resistivity increased. These effects could be explained by the amount of Mo2C. Fine particles of Mo2C provided crack initiation and growth sites to cause fracture. However they prevented the propagation of wear cracks. Eutectic carbides should be controlled within about 35 vol% considering a balance between mechanical properties and wear resistivity.

When the blade of the windmill crosses with the tower in wind power generation system, the wind pressure that blows against the blade becomes weak and the rotor speed decreases. This is called tower shadow effect. This paper proposes the method used stator-flux-oriented vector control to prevent the effect of the tower shadow for the wind generator system with a wound rotor induction generator. This paper shows that the proposed control method is effective because the power variation is a little even if the rotor speed changes by the effect of the tower shadow. Furthermore by comparison between vector control and slip frequency control, it is confirmed that the performance of the vector control has been excellent.

In many cases of radiolucent foreign bodies in the airway of infants, diagnosis is difficult. The diagnostic method has been mainly to detect Holzknecht's sign through conventional radiography. However, it has been difficult to obtain highly reliable information for detecting foreign bodies or determining the site of the foreign bodies by this diagnostic method alone.The recently developed digital radiography utilizes digital signals which are converted from X-ray energy to get clear images. The image processor which consists of a high speed computer, mathematically integrates the signals to visualize the spacific site. Digital fluorography, in particular, is widely applied clinically in vascular radiography in the form of digital subtraction angiography. The authors applied digital fluorography to two infants cases of radiolucent foreign bodies (peanuts) in the airway. The results suggested that the method could be usefully applied to diagnose foreign bodies in the airway and to detect the sites of the foreign bodies.

A case of suppurative arthritis by Serratia Marcescen was reported.The patient was a sixty-seven years old male who complained of pain and swelling in his right hip.Roentgenographically in this case, destructive changes in the femoral head and acetabulum had been obsered within short duration. Especially disappearance of the femoral head had been observed within about three weeks.Serratia Marcescens was verified in bacteria culture from joint fluid and synovial tissue.Focal curettage and medication of Astromycin 400mg/day and Flomoxef sodium 2g/day for about a month post-operation, were administered, and thereafter his symptom and laboratory data, including C-reactive Protein and erythrocyte sedimentation rate, were improved.He was satisfied with the result of our treatment though using the hip brace.

The effect of a zinc-containing compound, Polaprezinc, was shown to clinically improve the disease conditions of idiopathic taste disorders with no serious side effects in a well controlled double-blinded clinical study.The purpose of the present study was to evaluate the efficacy and safety of a zinc-containing compound in the treatment of patients with idiopathic taste disorders, including patients with low serum zinc, by a Good Clinical Practice (GCP)-compliant, randomized, placebo-controlled, double-blind, multi-center clinical study.A group of 109 patients suffering from taste disorders was assigned into placebo and three treatment groups. Each group of patients was given either placebo (n=28), or 17 mg (n=27), 34 mg (n=26) or 68 mg (n=28) of oral zinc, Polaprezinc preparations, daily for 12 weeks.The group of patients given 68 mg zinc showed a significant improvement in their gustatory sensitivity compared with the placebo group. The most common side effects observed were increase in serum triglyceride and serum alkaline phosphatase, decrease in serum iron, and some gastrointestinal incidents, although they were not serious.

A lengthy alteration of gravity direction produced different effects on the intrinsic horizontal and vertical optokinetic oculomotor systems.To examine both optokinetic nystagmus (OKN) and optokinetic after-nystagmus (OKAN) in a 6 h 6 degrees head-down bedrest study, in which the subjects were kept lying under simulated micro-gravity conditions.In six normal healthy adults, we repeatedly (five times) and comparatively studied OKN and OKAN evoked by horizontal and vertical stimuli. Stage 1 was an upright sitting position. During the 6 h bedrest condition, we studied OKN and OKAN in 90 degrees recumbent lateral positions (stages 2, 3, and 4). In stage 5 the subject returned to an upright position.We confirmed that the change in gravity direction had various effects on the condition of OKN and OKAN. Also, we found that it took more than 3 h to reach a desirable level of systemic adaptive modification to the unique environmental condition. We considered that the early change was basically due to the changes in sensory inputs through the otolith organs, and the latter changes represented the adaptive process of the spatial orientation system. During the tilt, the occurrence rates of both horizontal and vertical OKANs were decreased; however, the conditions of these changes were different.

This paper discusses a role of the oxygen vacancy in HfO2/ultra-thin (UT) interfacial layer (IL) SiO2 gate stacks, focusing on the VFB roll-off. The metal/top-SiO2/HfO2/UT IL-SiO2/Si gate stacks have been studied. It is found for the first time that the VFB roll-off is eliminated by inserting 1~2 nm top-SiO2 between metal gate and HfO2. This elimination of the VFB roll-off is explained by compensating the bottom dipoles at HfO2/IL-SiO2 interface with the counter dipoles at top-SiO2/HfO2 interface. Therefore it is concluded that the bottom dipole is assigned to the dominant origin of the VFB roll-off.

We have investigated effects of the oxygen doping into TaCx on the effective work function (Phim,eff) in TaCx/SiO2/Si and TaCx/HfO2/Si gate stacks. It has been found for the first time that the threshold voltage (Vth) is tunable within 0.5~0.6V for HfO2 MOSFETs by adjusting the oxygen content within 0~12 at. % in TaCx. Furthermore, it has been shown that unknown oxygen content in TaCx gates is a possible origin of scattering among the Phim.eff data reported.

Fifty four patients with a frozen shoulder, in which closed manipulation was done, were examined as to their clinical results.Further, 33 of them were examined by arthrography and articular capacity of the shoulder.We performed manipulation and operative procedures for the frozen shoulder in patients who had not responded to conventional conservative modalities such as antiinflammatory drugs, steroid injections, nerve block and physical therapy.In cases that the articular capacity in the shoulder was more than 12ml, or expansion of rotator interval region was held comparatively in the scapular Y view of arthrography, in less than 11ml, a full range of motion was obtained by closed manipulation under general anesthesia.As to the manipulation procedure, care should be taken not to do forced manipulation and manipulation should be done as gently as possible.Post operative management is most important in determining the prognosis of the patients.The key is to maintain the shoulder at an elevated position and to resume exercise therapy at an early stage.

Acyclovir, an antiviral agent, was administered to six patients with Ramsay Hunt syndrome, which induced complete facial paralysis and consulted within one week of the onset of facial paralysis. Complete recovery of paralysis was noted in four patients. The remaining two patients with incomplete recovery were in their fifties or older, and one of the two patients had shown no response to the nerve exitability test (NET) on the paralyzed side.In the present study, the effect of acyclovir on the prognosis of facial paralysis of Ramsay Hunt syndrome was relatively favorable.

BACKGROUND. Although genetic abnormalities on 3p have been suggested to be linked to the development of squamous cell carcinoma of the head and neck, to the authors' knowledge no study to date has examined such genetic abnormalities in patients with squamous cell carcinoma of the tongue. In the current study, loss of heterozygosity (LOH) was evaluated at several loci within 3p, including the von Hippel-Lindau gene (VHL), in samples of tongue squamous cell carcinoma. In addition, the coding region of the intact VHL allele was screened for sequence mutations. METHODS. DNA was extracted from tumor and nontumor tissues collected from 28 patients with tongue squamous cell carcinoma. LOH was investigated by analysis of single nucleotide polymorphisms within exon 3 of VHL and by microsatellite analysis within another 10 loci. Mutation analysis of the VHL gene was performed by polymerase chain reaction (PCR) amplification and sequencing of the coding region of the gene. RESULTS. LOH within VHL was found at a high frequency (45.5%) within the tumor. However, mutations of the VHL gene were not detected in all tumor samples. LOH of other microsatellite markers on 3p was observed in 27.3% to 50% of tumor samples. Eleven (58%) of 19 samples that were informative at more than 2 loci exhibited LOH of at least 1 locus; 10 of these 11 cases exhibited LOH at multiple loci. CONCLUSIONS. A wide range of deletions in 3p, including at the VHL gene, may play a role in the development of tongue cancer. Cancer 2008. © 2007 American Cancer Society.

Objectives:To determine the characteristics of causative factors of taste disorders amongst the elderly, and to examine the therapeutic effect of a zinc agent, taking into account age-related factors.Subjects:A total of 408 patients with taste disorders were divided into three groups by age: 49 years or younger, 50 to 64 years old, and 65 years or older.Results:The incidence of taste disorders caused by drug administration and systemic disease were significantly higher in the elderly group. A serum zinc concentration of 69 µg/dl or lower was found in 33 per cent of the elderly group, significantly more (p Conclusions:In the elderly, the incidence of taste disorders caused by drug administration or systemic disease was significantly greater compared with other age groups. The curative effects of zinc administration were not observed to be influenced by age.

We report for the first time that VFB roll-off behavior observed in thinner EOT region for metal/HfO2/SiO2 stacks is directly related to re-oxidation at the bottom SiO2/Si interface. Based on this understanding, we propose a possible solution for keeping high effective work-function (Phim,eff ) without VFB roll-off and demonstrate the obtained Phim,eff value of 4.9 eV mPt3Si/HfO2/SiO2 stack.

Purpose: Matrix metalloproteinases (MMP) play a fundamental role in cancer development and progression. S-3304 is a potent, orally active, noncytotoxic inhibitor of MMPs, primarily MMP-2 and MMP-9, that prolongs survival in mice xenografts and is well tolerated in healthy volunteers. Experimental Design: The aims of this phase I clinical trial were to determine the maximum tolerated dose, dose-limiting toxicities, pharmacokinetic profile, and intratumoral MMP inhibitory activity of single-agent S-3304 in advanced and refractory solid tumors. MMP activity was determined by film in situ zymography (FIZ). Patients had tumor biopsies before and after S-3304 administration and were also evaluated for response and survival. Results: Four dose levels were explored [DL1-DL4 or 800, 1,600, 2,400, and 3200 mg twice daily (BID), respectively], and 32 patients were enrolled. Toxicities were mostly gastrointestinal. The maximum tolerated dose was not reached, but dose escalations beyond DL4 were impractical (number of capsules needed). S-3304 steady-state concentrations were reached by day 8, and day 1 mean Cmax and AUC0-8 increases were less than dose proportional. After S-3304 administration, 17 of 18 patients experienced inhibition of MMP activity by FIZ. Strong mean inhibition of MMP activity was observed in DL1 to DL3. The negative mean inhibitory activity calculated for DL4 was due to one patient with a 397% MMP activity increase. Conclusion: S-3304 is safe, well tolerated, and achieves plasma concentrations above those required to inhibit MMP-2 and MMP-9. Its intratumoral MMP inhibitory activity has been shown using FIZ, which is useful as a biomarker with this and other MMP inhibitors.