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1.
BMC Infect Dis ; 19(1): 11, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30611204

RESUMO

BACKGROUND: Circulating interferon-γ (IFN-γ) concentration may be sustained at a high level regardless of the initiation of antiretroviral therapy (ART) in some patients with HIV-1 infection. In the present study, we examined the clinical characteristics of HIV-1-infected patients with high levels of plasma IFN-γ. METHODS: The study subjects were patients infected with HIV-1 who were either naïve to ART with CD4+ cell count > 200 cells/µL (n = 12), or had achieved viral suppression after ART for over a year (n = 188). The levels of plasma IFN-γ and interleukin-6 (IL-6) were measured by the enzyme-linked immunosorbent assay. Patients were divided into high IFN-γ and low IFN-γ groups based on a cutoff level of 5 pg/mL. RESULTS: The high IFN-γ group included 41 patients (21%). Compared to the patients on ART with low IFN-γ levels, those on ART in the high IFN-γ group were more likely to be younger than 50 years of age (P = 0.0051) and less likely to have dyslipidemia (P = 0.0476) or to be on a protease inhibitor (P = 0.0449). There was no significant difference between groups in the median increase of CD4+ cell counts from the initiation of ART for up to 3 years. However, after 4 years, the increase in CD4+ cell counts was significantly lower in the high IFN-γ group compared with that in the low IFN-γ group. There were no such significant differences between patients with low and high (> 2 pg/mL) levels of plasma IL-6. CONCLUSION: We concluded that HIV-1-infected patients with high levels of circulating IFN-γ did not have a higher rate of comorbidities related to immune activation. However, they exhibited lower CD4+ cell count recovery after 4 years of being on ART. This deficit could be a consequence of persistent immune activation.


Assuntos
Antirretrovirais/uso terapêutico , Farmacorresistência Viral/genética , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , HIV-1/genética , Interferon gama/sangue , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD4-Positivos/patologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Soropositividade para HIV/sangue , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , HIV-1/classificação , HIV-1/isolamento & purificação , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , RNA Viral/genética
3.
J Infect Chemother ; 23(1): 29-34, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27729193

RESUMO

The CCR5 antagonist, maraviroc (MVC), is associated with an enhanced CD4+ T-cell response independent of virological suppression; however, its mechanism of action has not been elucidated. In this study, we confirmed the effect of MVC on CD4+ T-cell count recovery in immunological non-responders, and compared the conventional combination antiretroviral therapy (cART) with MVC-intensified cART. We also investigated the effect of MVC on interferon-γ (IFN-γ) production in CD4+ T cells in vitro and in vivo, and evaluated the relationship between the mRNA level of IFN-γ and the degree of CD4+ T-cell count recovery. In vitro analysis indicated that MVC significantly decreased mRNA levels of IFN-γ in HIV-Tat stimulated CD4+ T cells from healthy donor peripheral blood mononuclear cells. Of the 18 HIV-infected patients treated with MVC-intensified cART, 12 had a significantly increased CD4+ T-cell count after 24 weeks of additional treatment with MVC. In patients exhibiting a response in CD4+ T-cell counts, mRNA levels of IFN-γ in CD4+ T cells were lower than those in patients showing a non-response at baseline and at week 24, while mRNA levels of IFN-γ decreased in both groups at 24 weeks. In conclusion, MVC decreased the mRNA level of IFN-γ in CD4+ T cells in vitro and in vivo, especially in patients whose CD4+ T-cell count increased significantly. We also found that the lower baseline IFN-γ mRNA level and the larger decreased rate of IFN-γ mRNA in CD4+ T cells were associated with a good response to MVC regarding CD4+ T-cell recovery.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Cicloexanos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Interferon gama/metabolismo , RNA Mensageiro/metabolismo , Triazóis/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Contagem de Linfócito CD4/métodos , Linfócitos T CD4-Positivos/metabolismo , Feminino , Infecções por HIV/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/virologia , Masculino , Maraviroc , Pessoa de Meia-Idade , RNA Viral/metabolismo , Carga Viral/efeitos dos fármacos
4.
Kansenshogaku Zasshi ; 89(2): 254-8, 2015 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-26552122

RESUMO

OBJECTIVE: Peumocystis pneumonia (PCP) is one of the common opportunistic infections with severe respiratory failure, and is sometimes life-threatening in patients with the acquired immunodeficiency syndrome. Although treatment for PCP is established, an appropriate treatment period has not been evaluated to clarify the risk factors for immune reconstitution inflammatory syndrome (IRIS) associated with PCP. METHOD: We retrospectively analyzed the clinical characteristics of risk factor, which are the treatment period for PCP, and 67Ga scintigraphy (Ga-S) at the 21st day from the start of the treatment for PCP, with 21 cases of PCP and HIV infection treated during 2005-2012 at Kyushu Medical Center. RESULT: The rate of residual uptake by Ga-S was assessed in 17 cases (81%). Four cases were diagnosed as being PCP-IRIS, and residual uptake by Ga-S was detected in all PCP-IRIS cases. The durations of the therapy were classified into three groups: 21 days, 28 days, and 35 days. All PCP-IRIS cases were treated in the period of 28 days. In contrast, in 11 cases that showed residual uptake by Ga-S, and were treated for PCP in 35 days, PCP-IRIS did not occur. Additionally, there were 4 cases in which residual uptake by Ga-S did not occur. They were treated with PCP for only 21 days, but did not show PCP-IRIS. CONCLUSION: In this study, we showed that Ga-S is useful to evaluate the therapeutic effect. Furthermore, we found that the occurrence of PCP-IRIS could be prevented with the early start of cART after 21 days treatment for PCP, when residual uptake by Ga-S after the first treatment for PCP was not detected. It may also be possible to start cART in the early phase after its treatment without the occurrence of PCP-IRIS with the appropriate additional treatment of PCP for 14 days. These guidelines for treatment of PCP in HIV-infected adults and adolescents have been recommended for the duration of 21 days since 1984. We propose that for the prevention of PCP-IRIS, it is nessecory to reconsider recommendation for the treatment duration of 21 days, and meanwhile to evaluate the treatment effect of PCP with Ga-S, because PCP resistance to sulfa drugs, namely are trimethoprim-sulfamethoxazole, is beginning to appear.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Radioisótopos de Gálio , Pneumonia por Pneumocystis/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/etiologia , Cintilografia
5.
Viruses ; 16(4)2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38675897

RESUMO

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4+ count, CD4+/CD8+ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4+ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , População do Leste Asiático , Infecções por HIV , Imunização Secundária , SARS-CoV-2 , Humanos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Masculino , Feminino , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Pessoa de Meia-Idade , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Infecções por HIV/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Adulto , Japão , Idoso , Vacinação , Contagem de Linfócito CD4
6.
Kansenshogaku Zasshi ; 87(4): 441-5, 2013 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-23984594

RESUMO

We present herein a case report of a 59-year-old patient with HIV-1 infection who developed a CMV-induced pseudotumor of the duodenum. The patient presented with oral pain and dysphagia. Physical examination revealed oral thrush. An EIA and a Western blot assay for antibodies to HIV were positive. His CD4-positive lymphocyte count was initially 49/microL with an HIV viral load of 2.6 x 10(5) copies/mL. Cytomegalovirus (CMV) reactivation was detected with the CMV antigenemia assay. He had CMV retinitis in both eyes with unilateral blurring. An endoscopic study revealed candida esophagitis, and a tumor-like lesion with an irregular ulcer at the papilla of Vater. Histological and immunohistochemical studies revealed a CMV-induced pseudotumor and severely inflamed duodenal mucosa with infiltration of CMV-positive cells. The patient was treated with oral valganciclovir and fluconazole for three weeks. As the oral thrush and retinitis showed improvement, he began antiretroviral therapy (ART), consisting of raltegravir and TDF/ FTC. One month later the patient's CD4-positive cells increased to 130/microL and the level of HIV-RNA decreased to 160 copies/mL, The CMV retinitis had transiently worsened because of an ART-induced inflammatory response, immune reconstitution inflammatory syndrome (IRIS). Six months after the ART initiation, an endoscopic study revealed that the esophagitis and the lesion at the papilla had improved. Biopsy showed no CMV-positive cells in the epithelium. The patient was now in a relatively healthy condition. CMV-induced pseudotumors of the duodenum are rare, and sometimes resemble malignancy. However, because this tomor responds to medical treatment physicians treating severely immunocompromised patients should be aware of its presentation and treatment.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/patologia , Ampola Hepatopancreática , Colangite/patologia , Infecções por Citomegalovirus/patologia , Infecções por HIV/complicações , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade
7.
Fukuoka Igaku Zasshi ; 103(1): 24-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22423500

RESUMO

We report the case of a 31-year-old woman who developed adult-onset Still's disease (AOSD) with a high level of serum interleukin (IL)-18. Although treated with high dose steroids, she suffered repeated remissions and her condition deteriorated. After we administered oral cyclosporine A (CsA), 200 mg/d, monitoring C2 and trough levels, her symptoms improved significantly. We decreased the dose of methylprednisolone slowly without noting a relapse. The use of CsA accompanied by C2 and trough level monitoring should be considered for refractory AOSD patients with high levels of serum IL-18.


Assuntos
Ciclosporina/administração & dosagem , Interleucina-18/sangue , Doença de Still de Início Tardio/sangue , Doença de Still de Início Tardio/tratamento farmacológico , Administração Oral , Adulto , Ciclosporina/sangue , Monitoramento Ambiental , Feminino , Humanos
8.
J Infect Chemother ; 17(2): 183-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20706762

RESUMO

Antiretroviral therapy for HIV infection is associated with lipodystrophy. However, raltegravir (RAL), a new integrase inhibitor, and atazanavir (ATV), a new generation of protease inhibitor (PI), have not been reported to significantly induce metabolic abnormalities in some clinical studies. The aim of this study was to investigate the influence and molecular mechanisms of RAL and compared it with the other three classes of ARVs (nucleoside reverse-transcriptase inhibitors; NRTI, nonnucleoside reverse-transcriptase inhibitor; NNRTI, and PI) on adipogenesis using 3T3-L1 cells. RAL and ATV had minimal effects on the lipid metabolism of 3T3-L1 cells. NRTI induced a moderate change, and NNRTI and some PIs induced a severe reduction in cell lipid content. These ARVs induced a decrease in the expression of genes associated with lipogenic transcription factors (sterol regulatory-element-binding protein-1c, CAAT box enhancer-binding protein-α, and peroxisome proliferator-activated receptor-γ). The differentiated 3T3-L1 cells were less sensitive to ARV-induced metabolic disturbance than were predifferentiated cells. RAL and ATV did not significantly affect the lipid metabolism in our in vitro study. The other ARVs had a direct influence on adipocytes. Degree and underlying mechanisms of metabolic disturbance differed among different ARVs. These data suggest that the distinct metabolic side-effect profiles of ARVs are a consequences of their differential effects on the adipocyte physiology. A better understanding of the mechanism of ARV-induced metabolic abnormalities could lead to safer use of ARVs or selection of alternative agents for further clinical development.


Assuntos
Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Fármacos Anti-HIV/farmacologia , Diferenciação Celular/efeitos dos fármacos , Oligopeptídeos/farmacologia , Piridinas/farmacologia , Pirrolidinonas/farmacologia , Células 3T3-L1 , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Animais , Fármacos Anti-HIV/classificação , Sulfato de Atazanavir , Regulação da Expressão Gênica , Inibidores de Integrase de HIV/farmacologia , Inibidores da Protease de HIV/farmacologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Estresse Oxidativo , Raltegravir Potássico , Inibidores da Transcriptase Reversa/farmacologia
9.
Mod Rheumatol ; 21(1): 76-8, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20680375

RESUMO

A 58-year-old woman was diagnosed with Churg-Strauss syndrome (CSS) based on the symptoms of bronchial asthma, eosinophilia, mononeuritis multiplex and histological examination of the right sural nerve. Prior to treatment, the serum interleukin (IL)-5 level was high, and rearrangement of the T cell receptor (TCR) gene was identified. This is the first report of TCR gene rearrangement in a patient with CSS. The expanded T cell clone may be responsible for the overproduction of IL-5. Further studies are warranted to disclose a prevalence of TCR gene rearrangement in CSS patients and its pathophysiological roles in the development of this disease.


Assuntos
Síndrome de Churg-Strauss/genética , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Genes Codificadores da Cadeia beta de Receptores de Linfócitos T , Interleucina-5/sangue , Síndrome de Churg-Strauss/sangue , Síndrome de Churg-Strauss/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Nervo Sural/patologia
10.
Mod Rheumatol ; 21(5): 557-60, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21547700

RESUMO

A 79-year-old man was diagnosed with relapsing polychondritis, from symptoms of bilateral auricular deformity and pigmentation, polyarthralgia, and audiovestibular damage, and from histological examination of the left auricular cartilage. The left auricular cartilage biopsy specimen revealed cartilage destruction with infiltration of plasmacytes expressing IgG4. This case suggests that IgG4 may be involved in the pathogenesis and etiology of relapsing polychondritis.


Assuntos
Adenocarcinoma/complicações , Doenças Autoimunes/imunologia , Imunoglobulina G/imunologia , Neoplasias Pulmonares/complicações , Policondrite Recidivante/imunologia , Adenocarcinoma/diagnóstico por imagem , Idoso , Doenças Autoimunes/complicações , Doenças Autoimunes/patologia , Biópsia , Orelha Externa/patologia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Plasmócitos/imunologia , Plasmócitos/patologia , Policondrite Recidivante/complicações , Policondrite Recidivante/patologia , Radiografia
11.
J Gastrointest Oncol ; 12(6): 2952-2959, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35070421

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection through unheated blood product for hemophilia caused in early 1980s has been significantly serious problem in Japan. After the development of HIV treatment in 1990s, HCV-related hepatocellular carcinoma (HCC) has been one of the most significant problem in these population. Treatment choices for HCC might be limited in hemophilia patients because of their bleeding tendency. The aim of this study was to elucidate the treatment choices and outcome of HCC in hemophilic patients coinfected with HIV/HCV due to contaminated blood products. METHODS: We asked 444 Japanese centers that specialize in treating HIV patients for participation, whether they have HIV/HCV coinfected cases with HCC, and the patient characteristics, treatments for HCC and survival after treatments were retrospectively reviewed according to each institutional medical records. RESULTS: Of 444 centers, 139 centers (31%) responded to the first query, and 8 centers (1.8%) ultimately provided 26 cases of HCC in coinfected hemophilic patients, diagnosed between December 1999 and December 2017. All 26 were male hemophilic patients, with a median age at HCC diagnosis of 49 (range, 34-73) years. Thirteen cases (50%) were HCV-RNA positive, and 14 cases (54%) had a solitary tumor. Even in the cases of Child-Pugh grade A, only 1 case underwent resection, and 18 cases (69%) did not receive the standard treatment recommended by the Japanese Society of Hepatology. CONCLUSIONS: Hemophilic HCC patients with HIV/HCV coinfection may not routinely receive standard treatment due to their bleeding tendency and several complications related to HIV/HCV coinfection.

12.
Eur J Haematol ; 84(6): 499-505, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20132301

RESUMO

Primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS) is a lethal disorder, but the recent application of highly active antiretroviral therapy (HAART) has significantly improved prognosis. This retrospective cohort study of AIDS-related PCNSL examined the actual clinical outcomes and prognostic variables affecting overall survival (OS) in the HAART era. Twenty-three newly diagnosed AIDS-related PCNSL at 12 regional centre hospitals for HIV/AIDS in Japan between 2002 and 2008 were consecutively enrolled. The estimated 3-yr OS rate of the entire cohort was 64% (95%CI, 41.0-80.3%). Whole brain radiation therapy (WBRT) had an independent positive impact on survival (WBRT >or=30 Gy vs. others, P = 0.02). Nine of 10 patients with a good performance status (PS) (0-2) remained alive with complete response, whereas 10 (77%) of 13 of those with a poor PS (3-4) died mostly after a short period. The estimated 3-yr OS rate of the groups with a good and poor PS was 100% and 38% (95%CI, 14-63%), respectively (P = 0.01). Leukoencephalopathy (grade >or= 2) developed in 21% of those that survived more than 12 months after radiation. The patients receiving a curative intent radiation dose (>or=30 Gy) of WBRT achieved prolonged survival while maintaining a good quality of life in the HAART era, especially among patients with a favourable PS.


Assuntos
Neoplasias Encefálicas/radioterapia , Linfoma Relacionado a AIDS/radioterapia , Adulto , Terapia Antirretroviral de Alta Atividade , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Leucoencefalopatias/etiologia , Linfoma Relacionado a AIDS/tratamento farmacológico , Linfoma Relacionado a AIDS/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Lesões por Radiação/etiologia , Dosagem Radioterapêutica , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
13.
Mod Rheumatol ; 20(2): 178-82, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19898920

RESUMO

We report a 24-year-old male with systemic lupus erythematosus (SLE) who developed influenza virus B-associated hemophagocytic syndrome and cardiac tamponade. Although the patient's general condition improved after steroid pulse therapy and pericardiocentesis, pericardial effusion re-accumulated. Colchicine and aspirin were administered, together with prednisolone, after which no further relapses occurred. This was a rare case of severe influenza-associated hemophagocytic syndrome and steroid-resistant pericardial effusion in an SLE patient.


Assuntos
Vírus da Influenza B , Influenza Humana/complicações , Lúpus Eritematoso Sistêmico/complicações , Linfo-Histiocitose Hemofagocítica/complicações , Pericardite/complicações , Anti-Inflamatórios/uso terapêutico , Aspirina/uso terapêutico , Colchicina/uso terapêutico , Quimioterapia Combinada , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/virologia , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Pericardite/diagnóstico por imagem , Pericardite/tratamento farmacológico , Prednisolona/uso terapêutico , Ultrassonografia , Adulto Jovem
14.
Fukuoka Igaku Zasshi ; 101(2): 34-40, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20560477

RESUMO

OBJECTIVE: To clarify the clinical usefulness of cerebrospinal fluid (CSF) interleukin-6 (IL-6) measurement in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), we studied CSF IL-6 levels in patients with NPSLE and analyzed the association between CSF IL-6 levels and other clinical findings of NPSLE. PATIENTS AND METHODS: We retrospectively analyzed records of 37 patients (33 females and four males) with NPSLE admitted to our hospital between January 2003 and December 2008. RESULTS: All patients showed neuropsychiatric symptoms. Fourteen patients showed abnormalities in brain magnetic resonance imaging (MRI) and 12 patients had abnormal findings in electroencephalography (EEG). Increased CSF cell counts and elevated levels of CSF IL-6 were found in 11 and 30 patients, respectively. Elevated levels of CSF IL-6 were not statistically correlated with specific abnormalities in the blood analysis, in increased CSF cell counts, and in abnormalities in the brain MRI and EEG. In addition, a group of NPSLE patients positive for antiphospholipid antibodies (aPL) showed lower CSF IL-6 than the patients negative for aPL. CONCLUSION: These results indicated that CSF IL-6 might be useful in diagnosis of NPSLE. However, general assessments of patients based on various factors (clinical manifestations, imaging findings and CSF examinations) are also required.


Assuntos
Interleucina-6/líquido cefalorraquidiano , Vasculite Associada ao Lúpus do Sistema Nervoso Central/líquido cefalorraquidiano , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Kansenshogaku Zasshi ; 83(3): 251-5, 2009 May.
Artigo em Japonês | MEDLINE | ID: mdl-19522309

RESUMO

Western blot (WB) is the most widely accepted confirmatory assay for detecting antibodies to the human immunodeficiency virus 1 (HIV-1). We report the case of an HIV-1 patient whose WB was negative for over two years. A 41-year-old Japanese man with Pneumocystis pneumonia (PCP) and pulmonary tuberculosis referred in March 2005 was found to have positive HIV-1 ELISA and HIV RNA PCR, but HIV-1 WB with only two bands, at gp160 and p18, and no WB HIV-2 band. The CD4 count was 37/microL, and total immunoglobulin, IgG, IgM, and IgG subclasses were normal. The man was treated for PCP and pulmonary tuberculosis, then underwent antiretroviral therapy. He had taken short-terms steroids to treat a drug allergy and immune reconstitution syndrome. Six months later, his serological ELISA tests for HIV-1 and HIV DNA PCR were negative and WB showed no positive band. The CD4 count recovered gradually, and exceeded 350/microL two years later, but WB remained negative. Lymphoproliferative assays and interferon y expression against HIV-pl7, p24, and p41 were studied and compared to those of other HIV-1 infected patients. Our patient showed no response to p17 or p24 and only a weak response to p41. Other patients showed a response to HIV-antigens, but patients with antiretroviral therapy or with histories of steroid use responded more weakly than those with neither. These findings show that HIV-specific lymphocytes decline with antiretroviral therapy and steroid treatment within early HIV infection. It is therefore important to interpret negative serological tests carefully in patients such as ours.


Assuntos
Western Blotting , Infecções por HIV/imunologia , HIV-1/imunologia , Adulto , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
16.
PLoS One ; 14(6): e0218996, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31246986

RESUMO

Telomere length (TL) is a marker of cellular and biological aging. Human immunodeficiency virus (HIV) infection has been reported to be associated with short TLs, which suggests that accelerated biological aging occurs in some cellular compartments of HIV+ individuals. In this study, we measured the TLs of peripheral leukocytes of HIV+ and healthy individuals and examined the biological and environmental correlates of TL. We also investigated the influence of TL on leukoaraiosis, an indicator of cerebral small vessel disease, in HIV+ individuals. Three hundred and twenty-five HIV+ individuals who received stable combination antiretroviral therapy (cART) for >1 year and achieved viral loads of <40 RNA copies/mL were enrolled along with 147 healthy individuals. Relative TLs of leukocytes were estimated by quantitative real-time polymerase chain reaction. Leukoaraiosis was assessed in 184 HIV+ individuals by fluid-attenuated inversion recovery magnetic resonance imaging. We analyzed several covariates, including markers of HIV infection, cART, and social/environmental factors; variables associated with TL length in univariate analyses were incorporated into multivariate models. The TLs of peripheral leukocytes of HIV+ individuals were significantly shorter than those of healthy individuals, and the rate of LT length decline with increasing age was greater. Linear regression analysis showed that in HIV+ individuals, increasing age, cART without integrase-stand transfer inhibitors (INSTI), failure to achieve viral loads of <40 copies/mL within 1 year of initiating cART, and substance use were significantly associated with shorter TLs, even after adjustment for the effects of age. Logistic regression analysis indicated an increasing risk of leukoaraiosis was associated with older age, shorter TLs, hypertension, and carotid artery plaque. Multivariate regression analysis indicated that older age and shorter TLs were significant risk factors for leukoaraiosis. In summary, our data showed that TL shortening in HIV+ individuals was independently associated with leukoaraiosis, and was associated with age, control of viral loads, use of INSTI, and substance use. Our results suggest that effective viral control and less toxic cART can help reduce TL shortening and improve outcomes among HIV+ individuals.


Assuntos
Infecções por HIV/genética , Leucoaraiose/diagnóstico por imagem , Leucócitos/química , Telômero/genética , Adulto , Fatores Etários , Idoso , Antirretrovirais/uso terapêutico , Estudos de Casos e Controles , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Leucoaraiose/genética , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Encurtamento do Telômero , Adulto Jovem
17.
Nihon Rinsho Meneki Gakkai Kaishi ; 30(2): 133-8, 2007 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-17473516

RESUMO

We herein report the successful use of rituximab in a 55-year-old woman with refractory PR3-ANCA-associated Wegener's granulomatosis. She responded to treatments with high dose methylprednisolone (mPSL), oral and intravenous cyclophosphamide, intravenous gammaglobulin, immunoabsorption, oral prednisolone (PSL), and oral ciclosporin, although she frequently relapsed with various symptoms, such as perforation of the small intestine, scleritis, orbital granuloma, complete AV block, multiple lung nodules, cerebellar infarction, and pharyngeal granuloma with a high level of PR3-ANCA. During her latest relapse, she was given high dose mPSL and 2 infusions of 600 mg (375 mg/m(2)) of anti-CD20 monoclonal antibody rituximab with an interval of 4 weeks, followed by a tapering of the administered PSL. The patient's PR3-ANCA levels normalized within 2 months, but at 6 months after the beginning of the administration of rituximab, the PR3-ANCA level gradually increased without any clinical symptoms. Therefore, two more infusions of rituximab were again administered and thereafter the PR3-ANCA level finally normalized. At present, at 14 months after the initial rituximab treatment, the patient's remission continues to be maintained. The successful treatment of this patient by rituximab therefore suggests that it is an effective and new therapeutic approach for the treatment of refractory Wegener's granulomatosis.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Granulomatose com Poliangiite/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Anticorpos Monoclonais Murinos , Feminino , Granulomatose com Poliangiite/imunologia , Humanos , Pessoa de Meia-Idade , Rituximab
18.
Hum Antibodies ; 14(3-4): 81-8, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16720978

RESUMO

By immunizing mice sequentially with six different V3 peptides we obtained a murine monoclonal antibody (MAb) C25, and its humanized counterpart KD-247. The MAb recognizes the sequence IGPGRA at the tip of the V3 loop and displays broad neutralizing activity against a variety of HIV-1 isolates. KD-247 was tested in an ex vivo neutralization assay to determine its capability to contain the spread of a quasi species population of clade B HIV-1 derived from two patients. The epitope of KD-247 was generally matching with the V3 sequences of various clones isolated from plasma and peripheral blood mononuclear cells (PBMC) of two patients. Complete or strong inhibition of viral replication was observed when the patients' PBMC were cultured with a high concentration of KD-247. Some neutralization escape variants, which had mutations in the V3 or outside of the V3 loop, emerged only at a low concentration of the MAb. These results suggest that KD-247 could be a good candidate for immunotherapy against HIV-1 in vivo.


Assuntos
Anticorpos Monoclonais/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/terapia , HIV-1/imunologia , Fragmentos de Peptídeos/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Monoclonais/uso terapêutico , Mapeamento de Epitopos , Anticorpos Anti-HIV/imunologia , Proteína do Núcleo p24 do HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/imunologia , Humanos , Leucócitos Mononucleares/imunologia , Camundongos , Dados de Sequência Molecular , Testes de Neutralização/métodos , Replicação Viral
19.
Artigo em Japonês | MEDLINE | ID: mdl-27118334

RESUMO

OBJECTIVE: To investigate clinical and laboratory features of giant cell arteritis (GCA). METHOD: We included 24 patients (6 men, 18 women; mean age 69.8 years) in this study. GCA was diagnosed based on the American College of Rheumatology 1990 classification criteria. RESULTS: Mean serum C-reactive protein was 9.03 mg/dl. GCA was classified into three types: classic temporal arteritis type (cranial GCA, nine patients); large-vessel type, affecting the aorta and its major branches without temporal arteries (12 patients); generalized type, affecting both temporal arteries and large vessels (three patients). Swelling and tenderness of temporal arteries were recognized in temporal arteritis and generalized arteritis. Ten of these patients also had histopathologic findings of arteritis, including giant cells in biopsy specimens. Examination of HLA-class 1 expression showed that one patient with cranial GCA, three with generalized GCA, and seven with large-vessel GCA were positive for HLA-A24, and four patients with large-vessel GCA were positive for HLA-B39. One patient with cranial GCA, one with generalized GCA, and six with large-vessel GCA were positive for HLA-B52. Nine patients were positive for anti-phospholipid antibodies (seven for anti-cardiolipin antibody immunoglobulin G, seven for anti-cardiolipin ß2-glycoprotein-1 antibody, one for lupus anticoagulant). CONCLUSION: Our study demonstrated that HLA-class 1 expression in GCA resembles that in Takayasu arteritis, suggesting that these two arteritis types share the same genetic background. In contrast, the difference in the prevalence of anti-phospholipid antibodies in GCA and Takayasu arteritis patients shows a difference in the characteristic aspects of these two arteritis types.


Assuntos
Arterite de Células Gigantes/classificação , Arterite de Células Gigantes/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antifosfolipídeos/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Feminino , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/patologia , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Arterite de Takayasu
20.
Intern Med ; 54(2): 223-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25743017

RESUMO

Human immunodeficiency virus (HIV) infection disturbs the host's immune function and often coexists with various autoimmune and/or systemic rheumatic diseases with manifestations that sometimes overlap with each other. We herein present the case of a 43-year-old Japanese man infected with HIV who exhibited elevated serum creatine kinase and transaminases levels without any symptoms. He was diagnosed with autoimmune hepatitis, polymyositis and Sjögren's syndrome and received combined antiretroviral therapy (cART); however, the laboratory abnormalities persisted. We successfully administered cART with the addition of oral prednisolone, and the patient's condition recovered without side effects related to the metabolic or immunosuppressive effects of these drugs.


Assuntos
Infecções por HIV/epidemiologia , Hepatite Autoimune/epidemiologia , Polimiosite/etiologia , Prednisolona/uso terapêutico , Síndrome de Sjogren/epidemiologia , Adulto , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepatite Autoimune/tratamento farmacológico , Humanos , Masculino , Polimiosite/tratamento farmacológico , Síndrome de Sjogren/tratamento farmacológico
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