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Search Results: 1 - 10 of 1044 matches for " Shinichi Oka "
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Outcome of Vision Impairment and Diabetes Insipidus in Suprasellar Region Germinoma  [PDF]
Satoshi Utsuki, Hidehiro Oka, Yoshiteru Miyajima, Chihiro Kijima, Kiyotaka Fujii, Shinichi Kan
International Journal of Clinical Medicine (IJCM) , 2011, DOI: 10.4236/ijcm.2011.22016
Abstract: Aim: Many cases of suprasellar region germinoma occurs in diabetes insipidus (DI), but a patient initially may come to the hospital for the chief complaint of visual impairment. The aim of this study is to determine the etiology of initial symptom presentation and the outcomes of visual impairment and DI in suprasellar region germinoma. Methods: We investigated eleven cases of single lesion suprasellar germinomas that were diagnosed and treated in our hospital. For each, a magnetic resonance imaging (MRI) was performed. Results: At the hospital visit, decreased visual acuity was found in 5/11 cases, while DI was found in all cases. The decreased visual acuity was improved in 4/5 cases by treatment, but DI improved in only 2/11 cases. In 10 cases, DI occurred earlier than visual impairment. As the initial symptom, visual impairment occurred earlier than DI in only one case and did not improve by treatment. In this case, a pituitary stalk of the normal thickness could be identified by MRI, and the optic nerve was swollen. In ten cases except this case, no significant enlargement of optic nerve was detected, and a swollen pituitary stalk was confirmed. Conclusions: In suprasellar germinomas, it is rare, but the optic nerve can significantly swell at onset, while the pituitary stalk may be intact. In such cases, visual impairment occurs earlier than DI, and visual impairment may not be improved.
Slow Turnover of HIV-1 Receptors on Quiescent CD4+ T Cells Causes Prolonged Surface Retention of gp120 Immune Complexes In Vivo
Yasuhiro Suzuki, Hiroyuki Gatanaga, Natsuo Tachikawa, Shinichi Oka
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0086479
Abstract: Peripheral blood CD4+ T cells in HIV-1+ patients are coated with Ig. However, the causes and consequences of the presence of Ig+ CD4+ T cells remain unknown. Previous studies have demonstrated the rapid turnover of viral receptors (VRs) on lymphoma and tumor cells. The present study investigates the turnover of VRs on peripheral quiescent CD4+ T cells (qCD4s), which are the most abundant peripheral blood CD4+ T cells. Utilizing pharmacological and immunological approaches, we found that the turnover of VRs on qCD4s is extremely slow. As a result, exposure to gp120 or HIV-1 virions in vitro causes gp120 to remain on the surface for a long period of time. It requires approximately three days for cell-bound gp120 on the surface to be reduced by 50%. In the presence of patient serum, gp120 forms surface immune complexes (ICs) that are also retained for a long time. Indeed, when examining the percentages of Ig+ CD4+ T cells at different stages of HIV-1 infection, approximately 70% of peripheral resting CD4+ T cells (rCD4s) were coated with surface VRs bound to slow-turnover gp120-Ig. The levels of circulating ICs in patient serum were insufficient to form surface ICs on qCD4s, suggesting that surface ICs on qCD4s require much higher concentrations of HIV-1 exposure such as might be found in lymph nodes. In the presence of macrophages, Ig+ CD4+ T cells generated in vitro or directly isolated from HIV-1+ patients were ultimately phagocytosed. Similarly, the frequencies and percentages of Ig+ rCD4s were significantly increased in an HIV-1+ patient after splenectomy, indicating that Ig+ rCD4s might be removed from circulation and that non-neutralizing anti-envelope antibodies could play a detrimental role in HIV-1 pathogenesis. These findings provide novel insights for vaccine development and a rationale for using Ig+ rCD4 levels as an independent clinical marker.
Amebiasis in HIV-1-Infected Japanese Men: Clinical Features and Response to Therapy
Koji Watanabe,Hiroyuki Gatanaga ,Aleyla Escueta-de Cadiz,Junko Tanuma,Tomoyoshi Nozaki,Shinichi Oka
PLOS Neglected Tropical Diseases , 2011, DOI: 10.1371/journal.pntd.0001318
Abstract: Invasive amebic diseases caused by Entamoeba histolytica are increasing among men who have sex with men and co-infection of ameba and HIV-1 is an emerging problem in developed East Asian countries. To characterize the clinical and epidemiological features of invasive amebiasis in HIV-1 patients, the medical records of 170 co-infected cases were analyzed retrospectively, and E. histolytica genotype was assayed in 14 cases. In this series of HIV-1-infected patients, clinical presentation of invasive amebiasis was similar to that described in the normal host. High fever, leukocytosis and high CRP were associated with extraluminal amebic diseases. Two cases died from amebic colitis (resulting in intestinal perforation in one and gastrointestinal bleeding in one), and three cases died from causes unrelated to amebiasis. Treatment with metronidazole or tinidazole was successful in the other 165 cases. Luminal treatment was provided to 83 patients following metronidazole or tinidazole treatment. However, amebiasis recurred in 6 of these, a frequency similar to that seen in patients who did not receive luminal treatment. Recurrence was more frequent in HCV-antibody positive individuals and those who acquired syphilis during the follow-up period. Various genotypes of E. histolytica were identified in 14 patients but there was no correlation between genotype and clinical features. The outcome of metronidazole and tinidazole treatment of uncomplicated amebiasis was excellent even in HIV-1-infected individuals. Luminal treatment following metronidazole or tinidazole treatment does not reduce recurrence of amebiasis in high risk populations probably due to amebic re-infection.
Illicit Drug Use Is a Significant Risk Factor for Loss to Follow Up in Patients with HIV-1 Infection at a Large Urban HIV Clinic in Tokyo
Takeshi Nishijima, Hiroyuki Gatanaga, Hirokazu Komatsu, Misao Takano, Miwa Ogane, Kazuko Ikeda, Shinichi Oka
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072310
Abstract: Background Loss to follow up (LTFU) is an important prognostic factor in patients with HIV-1 infection. The impact of illicit drug use on LTFU of patients with HIV-1 infection is unknown in Japan. Methods A single center observational study was conducted to elucidate the impact of illicit drug use on LTFU at a large HIV clinic in Tokyo. LTFU was defined as those who discontinued their visits to the clinic for at least 12 months and were not known to be under the care of other facilities or have died within 12 months of their last visit. Patients who first visited the clinic between January 2005 and August 2010 were enrolled. Information on illicit drug use was collected in a structured interview and medical charts. Comparison of the effects of illicit drug use and no use on LTFU was conducted by uni- and multi-variate Cox hazards models as the primary exposure. Results The study subjects were 1,208 patients, mostly Japanese men, of relatively young age, and infected through homosexual contact. A total of 111 patients (9.2%) were LTFU (incidence: 24.9 per 1,000 person-years). Among illicit drug users and non users, 55 (13.3%) and 56 (7.1%) patients, respectively, were LTFU, with incidence of 35.7 and 19.2 per 1,000 person-years, respectively. Uni- and multi-variate analyses showed that illicit drug use was a significant risk for LTFU (HR=1.860; 95% CI, 1.282-2.699; p=0.001) (adjusted HR=1.544; 95% CI, 1.028-2.318; p=0.036). Multivariate analysis also identified young age, high CD4 count, no antiretroviral therapy, and no health insurance as risk factors for LTFU. Conclusions The incidence of LTFU among illicit drug users was almost twice higher than that among non users. Effective intervention for illicit drug use in this population is warranted to ensure proper treatment and prevent the spread of HIV.
Preemptive Therapy Prevents Cytomegalovirus End-Organ Disease in Treatment-Na?ve Patients with Advanced HIV-1 Infection in the HAART Era
Daisuke Mizushima, Takeshi Nishijima, Hiroyuki Gatanaga, Kunihisa Tsukada, Katsuji Teruya, Yoshimi Kikuchi, Shinichi Oka
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0065348
Abstract: Background The efficacy of preemptive therapy against cytomegalovirus (CMV) infection remains unknown in treatment-na?ve patients with advanced HIV-1 infection in the HAART era. Methods The subjects of this single-center observation study were126 treatment-na?ve HIV-1 infected patients with positive CMV viremia between January 1, 2000 and December 31, 2006. Inclusion criteria were age more than 17 years, CD4 count less than 100/μl, plasma CMV DNA positive, never having received antiretroviral therapy (ART) and no CMV end-organ disease (EOD) at first visit. The incidence of CMV-EOD was compared in patients with and without preemptive therapy against CMV-EOD. The effects of the CMV preemptive therapy were estimated in uni- and multivariate Cox hazards models. Results CMV-EOD was diagnosed in 30 of the 96 patients of the non-preemptive therapy group (31%, 230.3 per 1000 person-years), compared with 3 of the 30 patients of the preemptive therapy group (10%, 60.9 per 1000 person-years). Univariate (HR = 0.286; 95%CI, 0.087–0.939; p = 0.039) and multivariate (adjusted HR = 0.170; 95%CI, 0.049–0.602; p = 0.005) analyses confirmed that CMV-EOD is significantly prevented by CMV preemptive therapy. Multivariate analysis showed that plasma CMV DNA level correlated significantly with CMV-EOD (per log10/ml, adjusted HR = 1.941; 95%CI, 1.266–2.975; p = 0.002). Among the 30 patients on preemptive therapy, 7 (23.3%) developed grade 3–4 leukopenia. The mortality rate was not significantly different between the two groups (p = 0.193, Log-rank test). Conclusions The results indicate that preemptive therapy lowers the incidence of CMV-EOD by almost 25%. Preemptive therapy for treatment-na?ve patients with CMV viremia is effective, although monitoring of potential treatment-related side effects is required.
High Prevalence of Illicit Drug Use in Men Who Have Sex with Men with HIV-1 Infection in Japan
Takeshi Nishijima, Hiroyuki Gatanaga, Hirokazu Komatsu, Misao Takano, Miwa Ogane, Kazuko Ikeda, Shinichi Oka
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081960
Abstract: Objective To examine the prevalence of illicit drug use among men who have sex with men (MSM) with HIV-1 infection in Japan, where the life-time prevalence of illicit drug use in the general population is only 2.9%. Design A single-center cross-sectional study at a large HIV clinic in Tokyo, which treats approximately 15% of HIV-1 infected patients in Japan. Methods The prevalence of illicit drug use and the assciation of characteristics and social demographics of the patients with illicit drug use were examined. Patients who visited the clinic for the first time from 2005 to 2010 were enrolled. Relevant variables were collected using a structured interview and from the medical records. Multivariate logistic regression analyses were applied to estimate the odds of association of MSM over non-MSM HIV-infected patients with illicit drug use. Results 1,196 patients were enrolled. They were mostly Japanese men of relatively young age. Illicit drug use (including injection drugs) was reported by 35% of the patients (by 40% of MSM), and 4% were IDU while 5% were on methamphetamine. 2% of the population was arrested due to illicit drugs. MSM was significantly associated with illicit drug use (adjusted OR = 4.60; 95% CI, 2.88–7.36; p<0.01). Subgroup analysis of the patients stratified by three age groups (≤30, 31 to 40, and >40) showed that the odds of association of MSM with illicit drug use was the strongest in the youngest age group (≤30 years: adjusted OR = 7.56; 95% CI, 2.86–20.0; p<0.01), followed by the oldest (>40 years: adjusted OR = 6.15; 95% CI, 2.40–15.8; p<0.01), and the weakest in the group aged 31 to 40 (adjusted OR = 3.39; 95% CI, 1.73–6.63; p<0.01). Conclusions The prevalence of illicit drug use is high among MSM patients with HIV-1 infection in Japan. Effective intervention for illicit drug use in this population is warranted.
Is Ritonavir-Boosted Atazanavir a Risk for Cholelithiasis Compared to Other Protease Inhibitors?
Yohei Hamada, Takeshi Nishijima, Hirokazu Komatsu, Katsuji Teruya, Hiroyuki Gatanaga, Yoshimi Kikuchi, Shinichi Oka
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0069845
Abstract: Objective To compare the incidence of complicated cholelithiasis in patients receiving ritonavir-boosted atazanavir (ATV/r)- containing antiretroviral therapy with those on other protease inhibitors (PIs). Design We conducted a single-center retrospective cohort study of patients who started either ritonavir-boosted ATV/r- or other PIs (ritonavir-boosted fosamprenavir, unboosted fosamprenavir, lopinavir/ritonavir, and ritonavir-boosted darunavir) -containing antiretroviral therapy. Methods The incidence of complicated cholelithiasis was determined in each group. Complicated cholelithiasis was defined as follows: 1) cholelithiasis complicated by cholecystitis, cholangitis, or pancreatitis or 2) symptomatic cholelithiasis or choledocholithiasis which required invasive procedures such as cholecystomy and endoscopic retrograde cholangiopancreatography. The effects of ATV/r were estimated by univariate and multivariate Cox hazards models as the primary exposure. Results Complicated cholelithiasis was diagnosed in 3 patients (2.23 per 1000 person-years) in the ATV/r group (n = 466), and 3 (1.64 per 1000 person-years) in the other PIs group (n = 776), respectively. The incidence was not statistically different in the two groups by log-rank test (P = 0.702). By univariate and multivariate analysis adjusted for age and body weight, ATV/r use was not associated with cholelithiasis. (HR = 1.365; 95% CI, 0.275–6.775; p = 0.704) (adjusted HR = 1.390; 95% CI, 0.276–7.017; p = 0.690). For the 3 patients who developed cholelithiasis in the ATV/r group, the time to the diagnosis of cholelithiasis was 18, 34, and 39 months, respectively. Conclusion In this study, the incidence of complicated cholelithiasis was low and was not different between patients on ATV/r and those on other PIs. On the contrary to ATV/r-associated nephrolithiasis, the possible risk of cholelithiasis should not preclude the use of ATV/r.
V3-Independent Competitive Resistance of a Dual-X4 HIV-1 to the CXCR4 Inhibitor AMD3100
Yosuke Maeda, Hiromi Terasawa, Yusuke Nakano, Kazuaki Monde, Keisuke Yusa, Shinichi Oka, Masafumi Takiguchi, Shinji Harada
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089515
Abstract: A CXCR4 inhibitor-resistant HIV-1 was isolated from a dual-X4 HIV-1 in vitro. The resistant variant displayed competitive resistance to the CXCR4 inhibitor AMD3100, indicating that the resistant variant had a higher affinity for CXCR4 than that of the wild-type HIV-1. Amino acid sequence analyses revealed that the resistant variant harbored amino acid substitutions in the V2, C2, and C4 regions, but no remarkable changes in the V3 loop. Site-directed mutagenesis confirmed that the changes in the C2 and C4 regions were principally involved in the reduced sensitivity to AMD3100. Furthermore, the change in the C4 region was associated with increased sensitivity to soluble CD4, and profoundly enhanced the entry efficiency of the virus. Therefore, it is likely that the resistant variant acquired the higher affinity for CD4/CXCR4 by the changes in non-V3 regions. Taken together, a CXCR4 inhibitor-resistant HIV-1 can evolve using a non-V3 pathway.
Nicotinamide Mononucleotide, an Intermediate of NAD+ Synthesis, Protects the Heart from Ischemia and Reperfusion
Takanobu Yamamoto, Jaemin Byun, Peiyong Zhai, Yoshiyuki Ikeda, Shinichi Oka, Junichi Sadoshima
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098972
Abstract: Nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme for nicotinamide adenine dinucleotide (NAD+) synthesis, and Sirt1, an NAD+-dependent histone deacetylase, protect the heart against ischemia/reperfusion (I/R). It remains unknown whether Nampt mediates the protective effect of ischemic preconditioning (IPC), whether nicotinamide mononucleotide (NMN, 500 mg/kg), a product of Nampt in the NAD+ salvage pathway, mimics the effect of IPC, or whether caloric restriction (CR) upregulates Nampt and protects the heart through a Sirt1-dependent mechanism. IPC upregulated Nampt protein, and the protective effect of IPC against ischemia (30 minutes) and reperfusion (24 hours) was attenuated at both early and late phases in Nampt +/? mice, suggesting that Nampt plays an essential role in mediating the protective effect of IPC. In order to mimic the effect of Nampt, NMN was administered by intraperitoneal injection. NMN significantly increased the level of NAD+ in the heart at baseline and prevented a decrease in NAD+ during ischemia. NMN protected the heart from I/R injury when it was applied once 30 minutes before ischemia or 4 times just before and during reperfusion, suggesting that exogenous NMN protects the heart from I/R injury in both ischemic and reperfusion phases. The protective effect of NMN was accompanied by decreases in acetylation of FoxO1, but it was not obvious in Sirt1 KO mice, suggesting that the effect of NMN is mediated through activation of Sirt1. Compared to control diet (90% calories), CR (60% calories for 6 weeks) in mice led to a significant reduction in I/R injury, accompanied by upregulation of Nampt. The protective effect of CR against I/R injury was not significant in cardiac-specific Sirt1 KO mice, suggesting that the protective effect of CR is in part mediated through the Nampt-Sirt1 pathway. In conclusion, exogenous application of NMN and CR protects the heart by both mimicking IPC and activating Sirt1.
Diagnostic value of antigenemia assay for cytomegalovirus gastrointestinal disease in immunocompromised patients
Naoyoshi Nagata, Masao Kobayakawa, Takuro Shimbo, Kazufusa Hoshimoto, Tomoyuki Yada, Takuji Gotoda, Junichi Akiyama, Shinichi Oka, Naomi Uemura
World Journal of Gastroenterology , 2011,
Abstract: AIM: To investigate the utility of the cytomegalovirus (CMV) antigenemia assay for the diagnosis of CMV gastrointestinal disease (GID).METHODS: One hundred and thirty immunocompromised patients were enrolled in this study. Patients with a history of anti-CMV treatment and who had not undergone examination using the antigenemia assay were excluded. CMV-GID was defined as the detection of large cells with intranuclear inclusions alone or associated with granular cytoplasmic inclusions by biopsy. Biopsy sections were stained with hematoxylin and eosin and immunohistochemically stained with anti-CMV. We evaluated the association between CMV-GID and patient characteristics (symptoms, underlying disease, medication, leukocyte counts, and antigenemia assay). All patients were checked with an human immunodeficiency virus (HIV) antibody test before endoscopic examination. White blood cell (WBC) counts were obtained from medical records within 1 wk of endoscopy. Leukopenia was defined as a total WBC count < 5000 cells/mm3. For HIV patients, we also checked CD4+ counts from medical records.RESULTS: A total of 99 patients were retrospectively selected for analysis. Of the immunocompromised patients, 19 had malignant disease, 18 had autoimmune disease, 19 had disorders of biochemical homeostasis, three had undergone transplantation, and 45 had HIV infection. A total of 50 patients had received immunosuppressive therapy. No patients had inflammatory bowel disease. Fifty-five patients were diagnosed as having CMV-GID. Univariate analysis indicated an association between HIV infection, leukopenia, and positive antigenemia and CMV-GID (P < 0.05). Multivariate analysis using logistic regression revealed that HIV infection and positive antigenemia were the only independent factors related to CMV-GID (P < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of antigenemia for CMV-GID were 65.4%, 93.6%, 91.9%, and 71.0%, respectively. In a subgroup analysis, patients with leukopenia displayed low sensitivity and high specificity. Minimal differences in accuracy were seen among patients with or without leukopenia. HIV-infected patients displayed low sensitivity and high specificity. Accuracy barely differed between HIV-positive and -negative patients. In HIV-infected patients, CD4 count < 50 cells/μL resulted in low sensitivity and high specificity. Differences in accuracy among patients were minor, regardless of CD4 count. In patients who had undergone both quantitative real-time polymerase chain reaction (PCR) and antigenemia assay,
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