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The Journal of Rheumatology 06/2012; 39(6):1291. · 3.69 Impact Factor
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ABSTRACT: Procalcitonin (PCT), a precursor for calcitonin, has been reported to be elevated in bacterial infection. However, its significance in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, who have treatment with corticosteroid and immunosuppressive drug, is limited. To investigate the usefulness of serum procalcitonin measurement in the diagnosis of bacterial infection in patients with systemic autoimmune diseases, we analyzed 28 patients with systemic autoimmune diseases hospitalized because of fever and/or C-reactive protein (CRP) elevation. PCT was measured by the immunochromatography assay. Fourteen patients were considered having bacterial infections and the other 14 patients were considered having disease flare of their systemic autoimmune diseases. Serum CRP levels in the bacterial infection group was higher than that in the systemic autoimmune disease flare group; however, the difference did not reach statistical significance. The positive rate of serum PCT was significantly higher in the bacterial infection group (10/14, 71%) than that in the systemic autoimmune disease flare group (1/14, 7%), although there were 2 cases showing false positive PCT probably due to rheumatoid factor. This study suggested that PCT is useful in the diagnosis of bacterial infection in patients with systemic autoimmune diseases who are treated with corticosteroid and immunosuppressive drug.
Rinsho byori. The Japanese journal of clinical pathology 04/2012; 60(4):294-9.
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Kunihiko Umekita,
Yumi Kaneko,
Kenji Yorita,
Yayoi Hashiba,
Motohiro Matsuda,
Shunichi Miyauchi,
Shiro Ueno,
Ichiro Takajo,
Norio Kusumoto,
Yasuhiro Nagatomo,
Kousuke Marutsuka, Akihiko Okayama
Rheumatology (Oxford, England) 11/2011; 51(3):580-2. · 4.24 Impact Factor
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ABSTRACT: High human T-lymphotropic virus Type 1 (HTLV-1) proviral DNA load (PVL) has been reported to be one risk factor for the development of adult T-cell leukemia/lymphoma (ATL). ATL is also believed to develop in HTLV-1 carriers who acquire infection perinatally. ATL cells have been reported to frequently harbor defective provirus. In our study, PVLs for three different regions of HTLV-1 provirus (5'LTR-gag, gag and pX) were measured in 309 asymptomatic carriers with different infection routes. PVLs for the pX region in 21 asymptomatic carriers with maternal infection was significantly higher than in 24 carriers with spousal infection. Among 161 carriers with relatively high pX PVLs (equal to or greater than 1 copy per 100 peripheral blood mononuclear cells), 26 carriers (16%) had low gag PVL/pX PVL (less than 0.5) and four (2%) had low 5'LTR-gag PVL/pX PVL (less than 0.5). Low gag PVL/pX PVL ratio, which reflects deficiency and/or polymorphism of HTLV-1 proviral DNA sequences for the gag region, was also associated with maternal infection. These data suggest that HTLV-1 carriers with maternal infection tend to have high PVLs, which may be related to provirus with deficiency and/or the polymorphism of proviral DNA sequences. In addition, there is a possibility that this ratio may be used as a tool to differentiate the infection routes of asymptomatic HTLV-1 carriers, which supports the need for a large scale study.
International Journal of Cancer 07/2011; 130(10):2318-26. · 5.44 Impact Factor
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ABSTRACT: We examined the educational usefulness of lung auscultation training with an auscultation simulator "Mr. Lung".
Auscultation training was conducted for fifth-year students of the Medical Department of the University of Miyazaki, and consisted of a lecture by a pulmonologist (Board Certified Member of the Japanese Respiratory Society) and skill training using Mr. Lung for a total of 90 min. We compared the percentages of students who correctly identified 4 adventitious sounds before and after training. We also investigated the responses to a self-report questionnaire on self-evaluation after training, auscultation experiences before training, and opinions regarding medical education with the simulator.
The subjects' correct answer rate before training was 40% or less and that for the correct identification of rhonchi was the lowest (5%). The correct answer rate, which was not influenced by previous experience of auscultation, significantly increased after training (80% or more). In the self-report questionnaire, about 90% of the students answered that the ability to identify lung sounds by auscultation was necessary for all doctors and that the simulator was effective for acquiring this skill.
The auscultation simulator may be useful for medical students not only to enhance auscultatory skills but also to realize the importance of auscultation in clinical examination.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 06/2011; 49(6):413-8.
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Hiroyuki Takenouchi,
Kazumi Umeki,
Daisuke Sasaki,
Ikuo Yamamoto,
Hajime Nomura,
Ichiro Takajo,
Shiro Ueno,
Kunihiko Umekita,
Shimeru Kamihira,
Kazuhiro Morishita, Akihiko Okayama
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ABSTRACT: Few studies have specifically examined defective provirus in asymptomatic human T-lymphotropic virus Type 1 (HTLV-1) carriers and its relation to proviral DNA loads (PVLs). To assess the significance of defective provirus in asymptomatic carriers, we examined PVLs in peripheral blood mononuclear cells of 208 asymptomatic HTLV-1 carriers. The mean PVLs determined using primers for the pol region were less than that for the pX region in these carriers. Analysis of seven carriers with high PVLs for the pX region but lower PVLs for the pol region showed that four had single nucleotide polymorphisms of proviral genomes for the pol region and three had HTLV-1-infected cells with defective provirus. Three carriers with defective provirus showed high PVLs at their initial screens, and PVLs increased after a 10- to 12-year interval in two carriers. Southern blot assay showed clonal expansion of HTLV-1-infected cells, and the predominant clones changed during the observation period. These data suggest that although HTLV-1-infected cells with defective provirus may have a growth advantage, the predominant clones of HTLV-1-infected cells do not always survive for many years in asymptomatic carriers.
International Journal of Cancer 03/2011; 128(6):1335-43. · 5.44 Impact Factor
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Kunihiko Umekita,
Shunichi Miyauchi,
Shiro Ueno,
Ichiro Takajo,
Kazunori Kusumoto,
Satoru Hasuike,
Yoshiko Umekita,
Hiroyuki Tanaka,
Kenji Nagata,
Yasuhiro Nagatomo,
Hiroaki Kataoka,
Kazuya Shimoda, Akihiko Okayama
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ABSTRACT: We report a case of rheumatoid arthritis (RA) with autoimmune hepatitis (AIH) and Sjogren syndrome (SjS) that was treated with the tumor necrosis factor (TNF) inhibitor, etanercept (ETN). Both RA activity and transaminase levels improved as a result of treatment. Follow-up liver biopsy showed improvement of hepatitis. Although the efficacy of anti-TNF for RA patients with AIH remains controversial, this case suggests that treatment with ETN may result in a favorable clinical course in a certain subset of patients with RA and AIH.
Internal Medicine 01/2011; 50(11):1245-9. · 0.94 Impact Factor
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Shimeru Kamihira,
Yoshihisa Yamano,
Masako Iwanaga,
Daisuke Sasaki,
Masahiro Satake, Akihiko Okayama,
Kazumi Umeki,
Ryuji Kubota,
Shuji Izumo,
Kazunari Yamaguchi,
Toshiki Watanabe
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ABSTRACT: Human T-cell leukemia virus type-1 (HTLV-1) proviral load (VL) is an important determinant of viral pathogenesis and malignant evolution. Although VL has been quantified by in-house real-time quantifiable polymerase chain reaction (qPCR) technology, little is known about the harmonization among different VL assay systems. We evaluated intra- and inter-laboratory variability of VL measured at six laboratories using the same DNA samples seropositive for HTLV-1 in a two-step manner. The first study measured 60 samples by original in-house assays, finding that the median intra- and inter-laboratory coefficient of variation (CV) was 44.9% (range, 25.4-71.8%) and 59.9% (34.2-93.4%), respectively. The inter-laboratory correlation coefficients ranged from 0.760 to 0.875, indicating that VL were measured with good precision in each laboratory, but inter-laboratory regression slopes differed from 0.399 to 2.206, indicating that VL were measured with a wide variation between laboratories. To examine the effect of standardization of reference materials (RM) on the VL variability, we performed a second study using only 20 samples by substituting RM for plasmid including the HTLV-1 pX region. The median inter-laboratory CV for raw pX copy number was reduced significantly from 66.9% to 35.7%, whereas the median CV for the internal control remained almost unchanged, resulting in no improvement in inter-laboratory CV for VL. This indicates that each in-house assay system worked well with good precision, but standardizing RM alone was insufficient for harmonization. The relevant choice of not only RM, but also internal control genes for data normalization is expected to be realistic to standardize HTLV-1 VL measurement.
Cancer Science 11/2010; 101(11):2361-7. · 3.33 Impact Factor
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Masaaki Watanabe,
Shingo Nakahata,
Makoto Hamasaki,
Yusuke Saito,
Yohei Kawano,
Tomonori Hidaka,
Kiyoshi Yamashita,
Kazumi Umeki,
Tomohiko Taki,
Masafumi Taniwaki, Akihiko Okayama,
Kazuhiro Morishita
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ABSTRACT: Human T-lymphotropic virus 1 (HTLV-1) causes an aggressive malignancy of T lymphocytes called adult T-cell leukemia/lymphoma (ATLL), and expression of HTLV-1 Tax influences cell survival, proliferation, and genomic stability in the infected T lymphocytes. Cyclin-dependent kinase inhibitor 1A (CDKN1A/p21(waf1/Cip1)) is upregulated by Tax, without perturbation of cell cycle control. During an analysis of the gene expression profiles of ATLL cells, we found very low expression of CDKN1A in ATLL-derived cell lines and ATLL cells from patient samples, and epigenetic abnormalities including promoter methylation are one of the mechanisms for the low CDKN1A expression in ATLL cells. Three HTLV-1-infected cell lines showed high levels of expression of both CDKN1A and Tax, but expression of CDKN1A was detected in only two of six ATLL-derived cell lines. In both the HTLV-1-infected and ATLL cell lines, we found that activated Akt phosphorylates CDKN1A at threonine 145 (T145), leading to cytoplasmic localization of CDKNIA. In HTLV-1-infected cell lines, cytoplasmic CDKN1A did not inhibit the cell cycle after UV irradiation; however, following treatment with LY294002, a PI3K inhibitor, CDKN1A was dephosphorylated and relocalized to the nucleus, resulting in suppression of the cell cycle. In the ATLL cell lines, treatment with LY294002 did not inhibit the cell cycle but induced apoptosis with the cytoplasmic localization. Therefore, the low CDKN1A expression in ATLL cells may be a key player in ATLL leukemogenesis, and the abnormal genomic methylation may influence the expression of not only HTLV-1 Tax but also CDKN1A during long-term development of ATLL from the HTLV-1-infected T lymphocytes.
Journal of Virology 07/2010; 84(14):6966-77. · 5.40 Impact Factor
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ABSTRACT: A 36-year-old woman was given a diagnosis of hemophagocytic syndrome associated with systemic lupus erythematosus, and was treated with high-dose methylprednisolone and etoposide. She needed endotracheal intubation for mechanical ventilation because of respiratory failure. She developed hoarseness and stridor 69 days after extubation. A pedunculated mass under her glottis was observed by the laryngoscopy. Development of a laryngeal granuloma due to long-term contact with the endotracheal tube was considered, although she was continuously given oral prednisolone (22.5 mg/day) even after extubation. She was treated with inhalation of fluticasone propionate and her symptoms, e.g. hoarseness, decreased. Disappearance of the polypoid lesion was seen on day 26. A laryngeal granuloma due to intubation developed, even with the systemic administration of steroids; but it was successfully treated with steroid inhalation.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 07/2010; 48(7):488-91.
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Masako Iwanaga,
Toshiki Watanabe,
Atae Utsunomiya, Akihiko Okayama,
Kaoru Uchimaru,
Ki-Ryang Koh,
Masao Ogata,
Hiroshi Kikuchi,
Yasuko Sagara,
Kimiharu Uozumi,
Manabu Mochizuki,
Kunihiro Tsukasaki,
Yoshio Saburi,
Masaomi Yamamura,
Junji Tanaka,
Yukiyoshi Moriuchi,
Shigeo Hino,
Shimeru Kamihira,
Kazunari Yamaguchi
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ABSTRACT: Definitive risk factors for the development of adult T-cell leukemia (ATL) among asymptomatic human T-cell leukemia virus type I (HTLV-1) carriers remain unclear. Recently, HTLV-1 proviral loads have been evaluated as important predictors of ATL, but a few small prospective studies have been conducted. We prospectively evaluated 1218 asymptomatic HTLV-1 carriers (426 males and 792 females) who were enrolled during 2002 to 2008. The proviral load at enrollment was significantly higher in males than females (median, 2.10 vs 1.39 copies/100 peripheral blood mononuclear cells [PBMCs]; P < .001), in those 40 to 49 and 50 to 59 years of age than that of those 40 years of age and younger (P = .02 and .007, respectively), and in those with a family history of ATL than those without the history (median, 2.32 vs 1.33 copies/100 PBMCs; P = .005). During follow-up, 14 participants progressed to overt ATL. Their baseline proviral load was high (range, 4.17-28.58 copies/100 PBMCs). None developed ATL among those with a baseline proviral load lower than approximately 4 copies. Multivariate Cox analyses indicated that not only a higher proviral load, advanced age, family history of ATL, and first opportunity for HTLV-1 testing during treatment for other diseases were independent risk factors for progression of ATL.
Blood 05/2010; 116(8):1211-9. · 9.90 Impact Factor
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ABSTRACT: The blood level of C-reactive protein and erythrocyte sedimentation rate reflect inflammation and are useful for the diagnosis of bacterial infection. However, these markers are often increased in other diseases such as rheumatoid arthritis. Procalcitonin (PCT), a precursor of calcitonin, was reported to be produced at the time of bacterial infection. The detection of PCT in blood is especially useful for the diagnosis of bacteremia. PCT is also considered to be useful for the diagnosis of limited bacterial infections, such as pneumonia, meningitis, and pyelonephritis, although the level in these conditions could be much less than that in bacteremia. There are two methods for the measurement of PCT in Japan: the chemiluminescence enzyme immunoassay (CLEIA) and immunochromatography assay (IC). CLEIA is quantitative and is sensitive for detecting a low level of PCT. IC is semi-quantitative and is useful for bed-side testing. It is important to understand the features of these two methods of PCT and to use them in appropriate situations.
Rinsho byori. The Japanese journal of clinical pathology 05/2010; 58(5):517-22.
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ABSTRACT: Successful engraftment of human T-lymphotropic virus type 1 (HTLV-1)-infected cells and a marked increase of proviral DNA loads (PVLs) in non-obese diabetic/severe combined immunodeficient (NOD/SCID)/gammac(null) (NOG) mice have been reported. Whether the increased PVL in transplanted mice is due to the new infection of HTLV-1 was examined.
Mononuclear cells from 3 NOG mice with primary engraftment from asymptomatic HTLV-1 carriers were transplanted into a second group of NOG mice. HTLV-1 PVL, proviral integration by fluorescence in situ hybridization assay, expression of viral antigen, and T-cell clonality were analyzed.
The PVLs in the secondarily transplanted NOG mice were significantly higher than those of primarily transplanted NOG mice. Multiple signals of HTLV-1 proviruses in the nucleus of the infected cells were revealed by fluorescence in situ hybridization analysis. Expression of HTLV-1 tax/rex mRNA and antigen was observed. The variety of T-cell clones was limited in the transplanted NOG mice.
Multiple proviral integrations were considered to be due to the new infection from HTLV-1-infected cells to the other cells. Only a certain fraction of T cells seemed to have selectively survived in NOG mice after engraftment.
Intervirology 03/2010; 53(4):229-39. · 2.34 Impact Factor
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Yoko Kikumoto,
Yasufumi Kai,
Hiroshi Morinaga,
Mutsunori Iga-Murahashi,
Mikitaro Matsuyama,
Takashi Sasaki,
Hiroki Maruyama,
Masaaki Shimotori,
Hirofumi Makino,
Hitoshi Sugiyama, Akihiko Okayama
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ABSTRACT: We describe two cases of Fabry disease in non-blood-related Japanese men, manifesting recurrent stroke even after the start of enzyme replacement therapy. Both exhibited chronic inflammation and ocular involvement with elevated levels of serum C reactive protein prior to the onset of stroke. We, therefore, suggest the association among persistent inflammation, ocular involvement and recurrent stroke in a certain subset of Fabry disease patients. Both cases received enzyme replacement therapy with no improvement in inflammatory signs or laboratory data. These cases suggest that Fabry disease should be considered in young patients with cryptogenic stroke or CNS manifestations and fever of unknown origin.
Internal Medicine 01/2010; 49(20):2247-52. · 0.94 Impact Factor
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Norio Kusumoto,
Masayuki Kuroki,
Kunihiko Umekita,
Shiro Ueno,
Ichiro Takajo,
Yasufumi Kai,
Yasuhiro Nagatomo,
Masami Shimada,
Tomonori Hidaka,
Kazuyoshi Kubo,
Syunnichi Miyauchi, Akihiko Okayama
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ABSTRACT: A 25-year-old man undergoing splenectomy at 3 years of age to treat idiopathic thrombocytopenic purpura but no history of Streptococcus pneumonia vaccination, and reporting high fever, nausea, and headache developed purpura, confusion, and hypotension the next day and was admitted. Detailed examination showed disseminated intravascular coagulation and multiple-organ dysfunction. Chest X-ray and computed tomography (CT) showed pneumonia and pleural effusion. Blood culture was positive for S. pneumoniae. Gram staining of sputa yielded numerous white blood cells and gram-negative rods, and sputa culture was positive for Pasteurella multocida and Haemophilus influenzae. The medical history and presence of these organisms yielded a diagnosis of overwhelming postsplenectomy infection (OPSI), and the patient responded to treatment with a combination of benzylpenicillin, cefotaxime, and meropenem. This case suggests that patients with a history of splenectomy may benefit from vaccination for S. pneumoniae and adequate education on OPSI.
Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 06/2009; 83(3):261-5.
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ABSTRACT: Microparticles (MPs) are believed to play an important role in inflammatory diseases such as rheumatoid arthritis (RA). Leukocytapheresis (LCAP) is one of the options available for the treatment of RA. We analyzed the levels of MPs in RA, by flow cytometry, especially in relation to the effect of LCAP. Twenty female patients with RA were recruited into this study. Six of the 20 patients with RA further received LCAP. Plasma levels of platelet-derived MPs were high in patients with RA and are correlated with disease activity. LCAP significantly improved RA in all six patients. The numbers of platelet-derived MPs significantly decreased after the first session of LCAP, which was probably due to direct removal by LCAP. Mean numbers of platelet-derived MPs after four sessions of LCAP markedly decreased. The numbers of granulocyte-derived MPs, which are suggested to have an anti-inflammatory effect, were markedly increased after the first session of LCAP. These data suggest that removal of platelet-derived MPs and increase of granulocyte-derived MPs are novel mechanisms of LCAP as effective treatment in RA.
Modern Rheumatology 05/2009; 19(3):265-72. · 1.58 Impact Factor
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Norio Kusumoto,
Yasufumi Kai,
Kazuyoshi Kubo,
Syunnichi Miyauchi,
Kunihiko Umekita,
Shiro Ueno,
Ichiro Takajo,
Yasuhiro Nagatomo, Akihiko Okayama,
Takuro Kameda,
Kazuya Shimoda
Nihon Naika Gakkai Zasshi 05/2009; 98(4):859-61.
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ABSTRACT: Few studies have specifically examined proviral load (PVL) and clonal evolution of human T-lymphotropic virus type 1 (HTLV-1)-infected cells in vertically infected children.
Sequential samples (from ages 1 to 16 years) from 3 HTLV-1-infected children (cases A, B and C) in the Jamaica Mother Infant Cohort Study were analyzed for their PVL and clonal expansion of HTLV-1-infected cells in peripheral blood mononuclear cells (PBMCs) by inverse-long PCR.
The baseline PVL (per 100,000 PBMCs) of case A was 260 (at 1 year of age) and of case B it was 1,867 (at 3 years of age), and they remained constant for more than 10 years. Stochastic patterns of clonal expansion of HTLV-1-infected cells were predominately detected. In contrast, case C, who had lymphadenopathy, seborrheic dermatitis and hyperreflexia, showed an increase in PVL from 2,819 at 1.9 years to 13,358 at 13 years of age, and expansion of 2 dominant clones.
The clonal expansion of HTLV-1-infected cells is induced in early childhood after infection acquired from their mothers. Youths with high PVL and any signs and symptoms associated with HTLV-1 infection should be closely monitored.
Intervirology 02/2009; 52(3):115-22. · 2.34 Impact Factor
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ABSTRACT: A 74-year-old woman with hepatitis due to hepatitis C virus followed up using oral predonisolone (3 mg/day) for two years because of hypergammaglobulinemia-associated purpura reported fever and lumbago in February 2005. Upon admission in June, she was found in chest-computed tomography to have atelectasia in the right middle lung lobe and a nodule with a cavity in the right lower lobe. She tested positive for tuberculous glycolipid antibody. Gallium scintigraphy showed an abnormal accumulation in the lower lumbar vertebra. Magnetic resonance imaging showed abnormal enhancement at L4, L5, and their intervertebral disc. Mycobacterium intracellulare (M. intracellulare) was detected in blood culture, bronchoalveolar lavage, and a biopsy specimen from the intervertebral disc, yielding a diagnosis of disseminated nontuberculous mycobacteriosis (NTM) due to M. intracellulare. She was treated with clarithromycin (CAM), ethambutol (EB), and rifampicin (RFP), but EB and RFP were discontinued due to of the fever they induced. She was then treated with a combination of CAM, levofloxacin, and streptomycin and followed up as an out patient. Based on case reports of disseminated NTM infection in Japan, the prognosis is poor and a protocol must be established for its treatment.
Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 12/2008; 82(6):644-9.
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ABSTRACT: The natural history of human T-lymphotropic virus type I (HTLV-I) has been shown to differ markedly by geographic area. The differences include contrasting patterns of risk of adult T-cell lymphoma (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which may be due in part to differences in host immune response to infection. To characterize variations in host immunity across populations, we compared serologic immune marker patterns in HTLV-I-endemic populations in Japan and Jamaica. We matched 204 participants with archived blood from the Miyazaki Cohort Study (Japan) and the Food Handlers Study (Jamaica)-i.e., 51 HTLV-I-positive ("carriers") and 51 HTLV-I-negative individuals ("noncarriers") from each population-by age, sex and blood collection year. We compared plasma concentrations of markers of T-cell-mediated (antigen-specific) and nonspecific immunity using regression models and correlation coefficients. Compared to Jamaican HTLV-I noncarriers, Japanese noncarriers had higher covariate-adjusted mean levels of T-cell activation markers, including antibody to Epstein-Barr virus nuclear antigen-1 (reciprocal titer 27 vs. 71, respectively, p=0.005), soluble interleukin-2 receptor-alpha (477 vs. 623 pg/mL, p=0.0008) and soluble CD30 (34 vs. 46 U/mL, p=0.0001) and lower levels of C-reactive protein (1.1 vs. 0.43 microg/mL, p=0.0004). HTLV-I infection was associated with activated T-cell immunity in Jamaicans but with diminished T-cell immunity in Japanese persons. The observed population differences in background and HTLV-I-related host immunity correspond closely to the divergent natural histories of infection observed among HTLV-I carriers in Japan and Jamaica and corroborate a role for host immune status in the contrasting patterns of ATL and HAM/TSP risk.
International Journal of Cancer 10/2008; 124(3):614-21. · 5.44 Impact Factor
