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Shinichi Oka

Publications and source records attributed to Shinichi Oka.

At least 37 records · Page 2Linked to original sources
PubMed2006

[Ocular complications in patients with human immunodeficiency virus infection].

PURPOSE: To evaluate the recent clinical manifestations of ocular complications in patients with human immunodeficiency virus(HIV) infection. METHODS: We retrospectively reviewed the medical records of 94 new HIV-positive patients examined at the International Medical Center of Japan between April 1, 2002, and March 31, 2003, and listed the details of ocular complications. The use of highly active antiretroviral therapy (HAART) and CD 4 cell counts was also recorded in patients with cytomegalovirus (CMV) retinitis and iritis/vitritis. RESULTS: The following ocular complications were recognized in 31 patients: retinal microvasculopathy (11 cases), CMV retinitis (10 cases), inactive inflammatory changes (6 cases), iritis/vitritis (5 cases), optic nerve atrophy (2 cases), papilledema (2 cases), ocular tuberculosis (1 case), progressive outer retinal necrosis (1 case) and conjunctival Kaposi's sarcoma (1 case). In patients with CMV retinitis, the CD 4 cell counts at the onset were lower than 50/microl except in 1 case. Iritis and/or vitritis were recognized in 5 cases, and the onset of 4 cases occurred after the beginning of HAART. Among the patients studied, immune recovery uveitis was suspected in 3 patients with a history of CMV retinitis. CONCLUSIONS: Ocular complications were recognized in almost one third of the patients in our series. Immune recovery uveitis was suspected in 3 patients with iritis/vitritis who previously had CMV retinitis.

Adult↗
PubMed2005

Mutations other than 103N in human immunodeficiency virus type 1 reverse transcriptase (RT) emerge from K103R polymorphism under non-nucleoside RT inhibitor pressure.

K103N mutation in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) confers high-level resistance against non-nucleoside RT inhibitors (NNRTIs) and it easily occurs partly because it arises by a single nucleotide substitution from wild-type K103. There are polymorphisms at codon 103 of HIV-1 RT. We found K103R polymorphic mutation in 3.3% of treatment-naive HIV-1-infected patients. R103N does not seem to occur as easily as K103N because R103N requires two nucleotide substitutions. To induce NNRTI resistance-associated mutations, HIV-1K103R was propagated in the presence of increasing concentrations of efavirez (EFV) or nevirapine (NVP). V179D emerged in all three EFV cultures and in two of four NVP cultures. R103G emerged by a single nucleotide substitution in one of three EFV cultures. R103N did not emerge in any of 7 NNRTI cultures. Analysis of recombinant HIV-1s showed that HIV-1K103R/V179D was significantly resistant and HIV-1K103G was moderately resistant against EFV and NVP.

Amino Acid Substitution↗
PubMed2005

Efficacy and immunologic responses to influenza vaccine in HIV-1-infected patients.

Influenza vaccine is recommended for HIV-1-infected patients. The present prospective study was conducted to evaluate the clinical efficacy and immunologic responses to the vaccine. From November 1 to December 27, 2002, 262 HIV-1-infected patients received a trivalent influenza subunit vaccine, whereas 66 did not. Influenza illness occurred in 16 vaccinated and 14 nonvaccinated patients (incidence = 6.1% [95% confidence interval (CI): 4%-10%] in vaccinated vs. 21.2% [CI: 13%-35%] in nonvaccinated persons, P < 0.001; relative risk = 0.29 [CI: 0.14-0.55]). Influenza vaccine provided clinically effective protection against influenza illness in HIV-1-infected patients. In baseline antibody-negative patients, anti-H1 and anti-H3 antibody responses to the vaccination were significant in those patients with a CD4 count >200 cells/muL compared with those with a CD4 count <200 cells/muL (P < 0.05). In contrast, in baseline antibody-positive patients, good antibody responses were observed irrespective of CD4 counts, like the healthy controls. Based on these results, annual vaccination is recommended. Specific CD4 responses correlated with HIV-1 viral load (VL), especially in patients treated with highly active antiretroviral therapy (HAART) compared with those without HAART (P < 0.01), although the clinical efficacy did not correlate with HIV-1 VL. HAART may enhance the immunologic efficacy of influenza vaccine.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Identification and characterization of HIV-1-specific CD8+ T cell epitopes presented by HLA-A*2601.

Since HLA-A*26 is one of the most common alleles in Asia, where approximately 20% of people have this allele, identification of HIV-1-specific epitopes presented by HLA-A*26 is necessary for studies on the immunopathogenesis of AIDS and vaccine development in Asia. As presented herein, we used the reverse immunogenetics approach to identify HIV-1 epitopes presented by HLA-A*2601, one of the major HLA-A*26 subtypes. We selected 24 HLA-A*2601-binding peptides out of 110 HIV-1 peptides by using a HLA-A*2601 stabilization assay. The ability of these HLA-A*2601-binding peptides to induce peptide-specific CD8(+) T cells was tested by stimulating PBMCs from HIV-1-infected individuals having HLA-A*2601 with these peptides. Four HLA-A*2601-binding peptides induced peptide-specific CD8 T cells. Analysis using HIV-1 recombinant vaccinia-infected C1R-A*2601 cells indicated that these four peptides were HIV-1 epitopes endogenously presented by HLA-A*2601. Two epitope-specific CD8(+) T cells were predominantly detected in HIV-1 infected individuals, suggesting that these epitopes may be useful for vaccine development.

Animals↗
PubMed2005

Modified Dynabeads method for enumerating CD4+ T-lymphocyte count for widespread use in resource-limited situations.

The Dynabeads method showed the potential for enumerating CD4 T lymphocytes (CD4 count) in HIV-1-infected individuals. The large volume of Dynabeads required for 1 sample and complex procedure made the method expensive and not easy for use, however. To decrease the cost and simplify the procedure, we reduced the volume of the Dynabeads, added wash times, and skipped over the staining step so as to count the CD4 cells directly under an optical microscope. The CD4 count of 246 blood samples using our modified Dynabeads method (DynabeadsCD4) showed a significant correlation with that obtained by flow cytometry (FlowcytoCD4) (r = 0.91 [P < 0.0001]; slope = 1.03, intercept = -16). The sensitivity and specificity for a CD4 count less than 200 cells/microL were 79% and 94%, and for a CD4 count less than 350 cells/microL, the sensitivity and specificity were 95% and 88%, respectively. The positive and negative predictive values for a CD4 count less than 350 cells/microL were 97% and 83%, respectively. The systematic error was 8 cells/microL (95% confidence interval [CI]: 0.4-16). The cost of Dynabeads for 1 sample was less than $1.00; thus, the estimated cost per DynabeadsCD4 test is less than $3.00, including the cost of other disposable materials. Our modified method is simple, economic, and accurate enough to monitor antiretroviral therapy in resource-limited situations.

Adult↗
PubMed2005

Cutting Edge: Epitope-dependent effect of Nef-mediated HLA class I down-regulation on ability of HIV-1-specific CTLs to suppress HIV-1 replication.

It is believed that Nef-mediated HLA class I down-regulation is one of the mechanisms that allow HIV-1-infected cells to escape from being killed by HIV-1-specific human CTLs. In this study, we show that the effect of Nef-mediated HLA class I down-regulation on the ability of HIV-1-specific CTLs to suppress HIV-1 replication is epitope dependent. The CTLs specific for two Pol epitopes presented by HLA-B*5101, one of the HLA alleles associated with slow progression to AIDS, effectively killed HIV-1-infected CD4+ T cells and suppressed HIV-1 replication. In contrast, those specific for the other four epitopes failed to kill HIV-1-infected CD4+ T cells and partially or hardly suppressed HIV-1 replication. The difference of the ability between these two types of CTLs may result from the difference of the number of HLA class I epitope complex on the surface of NL-432-infected CD4+ T cells.

Animals↗
PubMed2005

Survey of human immunodeficiency virus (HIV)-seropositive patients with mycobacterial infection in Japan.

OBJECTIVE: To assess DNA polymorphisms in mycobacterial isolates obtained from human immunodeficiency virus (HIV)-seropositive patients with tuberculosis in Japan from 1996 to 2003. METHODS: Restriction fragment length polymorphisms (RFLP) from Mycobacterium tuberculosis and Mycobacterium avium isolates obtained from individual seropositive patients with tuberculosis (n=78) were analysed with the use of IS6110 and (CGG)(5) or IS1245 and IS1311, respectively, as markers. As a control, the same procedures were applied to isolates from HIV-seronegative tuberculosis patients (n=87). RESULTS: Of 86 mycobacterial strains, M. tuberculosis, M. avium and Mycobacterium chelonae were identified in 48 (55.8%), 36 (41.9%) and 2 (2.3%) isolates, respectively. The obtained RFLP patterns of M. tuberculosis isolates from both the HIV-seropositive and -seronegative groups were variable, suggesting no obvious clustering among the isolates. Similar results were obtained in isolates of M. avium. CONCLUSIONS: This is the first report on the molecular epidemiology of Mycobacterium spp. isolated from HIV-seropositive patients in Japan. The results indicate that no particular clones of M. tuberculosis or M. avium prevail in HIV-seropositive patients in Japan. Further monitoring of mycobacterial infection associated with HIV infection in Japan should be continued.

Adolescent↗
PubMed2005

Patterns of cytokine production in human immunodeficiency virus type 1 (HIV-1)-specific human CD8+ T cells after stimulation with HIV-1-infected CD4+ T cells.

Although human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells can produce various cytokines that suppress HIV-1 replication or modulate anti-HIV-1 immunity, the extent to which HIV-1-specific CD8+ T cells produce cytokines when they recognize HIV-1-infected CD4+ T cells in vivo still remains unclear. We first analyzed the abilities of 10 cytotoxic T-lymphocyte (CTL) clones specific for three HIV-1 epitopes to produce gamma interferon, macrophage inflammatory protein 1beta, and tumor necrosis factor alpha after stimulation with epitope peptide-pulsed cells. These CTL clones produced these cytokines in various combinations within the same specificity and among the different specificities, suggesting a functional heterogeneity of HIV-1-specific effector CD8+ T cells in cytokine production. In contrast, the HIV-1-specific CTL clones for the most part produced a single cytokine, without heterogeneity of cytokine production among the clones, after stimulation with HIV-1-infected CD4+ T cells. The loss of heterogeneity in cytokine production may be explained by low surface expression of HLA class I-epitope peptide complexes. Freshly isolated HIV-1-specific CD8+ T cells with an effector/memory or memory phenotype produced much more of the cytokines than the same epitope-specific CTL clones when stimulated with HIV-1-infected CD4+ T cells. Cytokine production from HIV-1-specific memory/effector and memory CD8+ T cells might be a critical event in the eradication of HIV-1 in HIV-1-infected individuals.

CD4-Positive T-Lymphocytes↗
PubMed2005

Prediction of prolonged postprocedural hypotension after carotid artery stenting.

OBJECTIVE: Stent placement for the treatment of carotid artery stenosis may cause hemodynamic instability that induces ischemic complications for patients with bilateral carotid lesions. We carried out this study to define predictors of persistent hypotension after carotid stenting. METHODS: Thirty-three lesions in 31 consecutive patients (mean age, 69.2 +/- 8.6 yr) who underwent stent deployment for carotid stenosis were studied. Fourteen lesions were treated with Easy Wall stents (Boston Scientific, Tokyo, Japan) and 19 lesions were treated with Smart stents (Johnson & Johnson, Warren, NJ). We reviewed preoperative angiograms and ultrasonograms of the carotid artery and analyzed the predictive factors of postprocedural prolonged hypotension (systolic blood pressure < 90 mm Hg and periods > 3 h). RESULTS: Postprocedural hypotension was observed in 14 lesions (42.4%), of which medical treatment was necessary in seven (21.2%). A distance between carotid bifurcation and maximum stenotic lesion (< or = 10 mm; P = 0.0028) and type of stenosis (eccentric; P = 0.0287) on angiogram and fibrous plaque morphological features (P = 0.0008) and calcifications at carotid bifurcation (P = 0.0004) on ultrasonograms were determined to be independent risk factors of postprocedural hypotension. We introduced a scoring system for predicting prolonged hypotension that included factors such as the distance from carotid bifurcation to maximum stenotic lesion (< or = 10 mm), type of stenosis (eccentric), plaque morphological features (echogenic), and calcification at carotid bifurcation. The score was determined by adding one point for each of these factors. Three points or more on this score strongly suggested a high risk of prolonged hypotension. CONCLUSION: Our scoring system, which includes angiographic and ultrasonographic findings, may be a good index for the prediction of prolonged hypotension after carotid stenting and may contribute to the reduction of periprocedural ischemic events.

Adult↗
PubMed2004

Autologous transplantation of expanded neural precursor cells into the demyelinated monkey spinal cord.

The objective of this study was to establish if neural precursor cells could safely be developed from biopsy of the subventricular zone (SVZ) in the non-human primate (marmoset), and to determine their myelinating potential after autologous transplantation into a demyelinated lesion. Small amounts of tissue were safely collected from the subventricular-subependymal zone of the adult primate brain under ultrasonography without any neurological deficit. Neural precursor cells were isolated and expanded in the presence of mitogen in vitro. The dorsal columns of the adult marmoset spinal cord were demyelinated by X-irradiation and intraspinal injections of ethidium bromide in the center of the radiation field. Cell suspensions of the neural precursors were microinjected through a micropipette into the demyelinated lesion site in the spinal cord. Lesions were histologically examined 3 weeks after transplantation. Light and electron microscopic examination of plastic embedded sections revealed a significant number of myelinating profiles in the transplantation zone; no myelination was observed in control lesions. The myelinated axons had predominantly peripheral patterns of myelination. These results demonstrate that autologous transplantation of neural precursor cells in the adult nonhuman primate can remyelinate demyelinated central nervous system (CNS) axons, thus suggesting the potential utility of such an approach in demyelinating lesions in humans.

Animals↗
PubMed2004

Spontaneous recovery of hemoglobin and neutrophil levels in Japanese patients on a long-term Combivir containing regimen.

OBJECTIVE: In order to evaluate long-term toxicity of Combivir, we retrospectively reviewed clinical records of HIV-1 infected cases under treatment with Combivir-containing regimen and we analyzed the clinical data compared to other NRTIs-containing regimens. STUDY DESIGN: A total of 55 patients who were on Combivir and 39 on a control regimen were examined. RESULTS: After starting treatment with Combivir-containing regimens viral load and CD4(+) T-cell count improved as well as the control group. Rates of adverse events in Combivir group and ZDV (400 mg/day) + 3TC group were 50.9% (28/55) and 60% (12/20), respectively. Some of these Japanese patients who started Combivir regimen as a first-line HAART (primary Combivir group) showed some decrease in hemoglobin levels or neutrophil counts within 6 months. However, a significant recovery of these indices of hematological toxicities occurred in patients who continued the regimen for 18-24 months. CONCLUSION: Our findings suggest that the safety of 600 mg of ZDV is similar to 400 mg/day of ZDV and the existence of mechanisms that compensate for anemia and for the neutropenia associated with long-term use of Combivir.

Adult↗
PubMed2004

Functionally impaired HIV-specific CD8 T cells show high affinity TCR-ligand interactions.

We eventually isolated two different clonotypic CD8 T cell subsets recognizing an HIV Pol-derived epitope peptide (IPLTEEAEL) in association with HLA-B35 from a chronic HIV-infected patient. By kinetic analysis experiments, the subsets showed a >3-fold difference in half-lives for the HLA tetramer in complex with the Pol peptide. In functional assays in vitro and ex vivo, both subsets showed substantial functional avidity toward peptide-loaded cells. However, the high affinity subset did not show cytolytic activity, cytokine production, or proliferation activity toward HIV-infected cells, whereas the moderate affinity one showed potent activities. Furthermore, using ectopic expression of each of the TCR genes into primary human CD8 T cells, the CD8 T cells transduced with the high affinity TCR showed greater binding activity toward the tetramer and impaired cytotoxic activity toward HIV-infected cells, corroborating the results obtained with parental CD8 T cells. Taken together, these data indicate that impaired responsiveness of T cells toward HIV-infected cells can occur at the level of TCR-ligand interactions, providing us further insight into the immune evasion mechanisms by HIV.

CD8-Positive T-Lymphocytes↗
PubMed2004

Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naïve patients.

Several reports have recently shown that drug-resistant human immunodeficiency virus type 1 (HIV-1) is often isolated from treatment-naïve patients. We phenotypically analyzed HIV-1 strains isolated from 44 treatment-naïve individuals and found two strains highly resistant (69- and >310-fold) against nevirapine (NVP). Direct sequencing showed these two isolates had a novel mutation, K238S, in reverse transcriptase (RT), but did not have any reported NVP resistance-associated mutation. A 48-h culture in the presence of NVP, however, selected HIV-1 carrying NVP resistance-associated mutations, V106A, V108I, or both, suggesting that minor viral populations of these two isolates had harbored these mutations. Replication kinetic studies of recombinant HIV-1 clones suggested that K238S conferred a significant resistance against NVP, especially when accompanied with V106A (530-fold) or V108I (56-fold). Our study identified a novel NVP resistance-associated mutation, K238S, which could be persistently detected by genotypic assay longer than V106A and V108I during off-treatment period.

Adult↗
PubMed2004

Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma efavirenz concentrations in HIV-1 patients treated with standard efavirenz-containing regimens.

Efavirenz (EFV) is metabolized by cytochrome P450 2B6 (CYP2B6) in the liver. We analyzed the genotypes of CYP2B6 and their contribution to plasma EFV concentrations in 35 EFV-treated patients in International Medical Center of Japan. The mean plasma EFV concentration of patients with CYP2B6 *6/*6 (Q172H and K262R) (25.4+/-7.5 microM, +/-SD, n = 2) was significantly higher than that of patients with genotypes *6 heterozygote (9.9+/-3.3 microM, n = 10) or without alleles *6 (8.0+/-2.6 microM, n = 23) (p < 0.0001). To confirm our result, we further analyzed nine patients (three with high EFV concentrations and arbitrarily selected six with normal EFV concentrations) treated in Osaka National Hospital, and it resulted that the only three patients with the high concentrations were the *6/*6 holder. EFV dose could be decreased in those patients harboring the genotype to reduce toxicity with compromising potency, representing the first step of the Tailor-Made therapy of HIV-1 infection.

Alkynes↗
PubMed2004

Viral load of human herpesvirus 8 (HHV-8) in the circulatory blood cells correlates with clinical progression in a patient with HHV-8-associated solid lymphoma with aids-associated Kaposi's sarcoma.

We encountered a case of a rapidly progressive HHV-8-associated solid lymphoma with AIDS-associated Kaposi's sarcoma (KS). HHV-8 DNA load in whole blood cells was analyzed quantitatively by real-time PCR using amplification of the HHV-8-encoded ORF26 gene. Ours is the first observation that the rapid increase in the HHV-8 viral load (from 1.9x10(4) copies/microg to 1.6x10(6) copies/microg in 40 days) in conjunction with low CD4+ cell counts was accompanied by an accelerated clinical disease progression. The results indicate that the quantity of circulating HHV-8 is measurable with real-time PCR and can provide clinically useful information.

AIDS-Related Opportunistic Infections↗
PubMed2004

A discriminative study of health-related quality of life assessment in HIV-1-infected persons living in Japan using the Multidimensional Quality of Life Questionnaire for persons with HIV/AIDS.

The aim of this study is to evaluate the discriminative properties of the Multidimensional Quality of Life Questionnaire for HIV infection (MQoL-HIV) and to determine those factors contributing to the health-related quality of life (HRQoL) of HIV-1 infected persons living in Japan. The MQoL-HIV, the Nottingham Health Profile (NHP) as a generic instrument, and the Center for Epidemiologic Studies-Depression Scale (CES-D) as a psychological measure were administered in 375 patients as a multiple-centre study. The score distribution of the MQoL-HIV showed a unimodal distribution. The Cronbach's alpha coefficient scored more than 0.7 in seven out of 10 domains, but was low in both the physical functioning and sexual functioning domains. There was a strong correlation between the CES-D and MQoL-HIV index scores (R-0.73). Relatively high coefficient values were found between psychiatric and nervous symptoms and the index score (R=-0.60). In total, the MQoL-HIV may possess discriminative properties.

Adult↗
PubMed2003

Dilated cardiomyopathy in an adult human immunodeficiency virus type 1-positive patient treated with a zidovudine-containing antiretroviral regimen.

We describe an adult woman infected with human immunodeficiency virus type 1 (HIV-1) who developed dilated cardiomyopathy (DCM) with histologically confirmed mitochondrial damage while receiving anti-HIV-1 combination therapy that included nelfinavir, lamivudine, and zidovudine. DCM resolved after discontinuation of the regimen, and cardiac function remained normal after initiation of treatment with nelfinavir, lamivudine, and abacavir, which indicates that DCM was induced by mitochondrial toxicity, most likely caused by zidovudine.

Adult↗