Streptococcus taonis sp. nov., a novel bacterial species isolated from a blood culture of a patient.

One Gram stain-positive, catalase-negative, α-hemolytic, chain-forming or paired cocci, designated ST22-14T, was isolated from a blood culture of a child with suspected infection. The results of 16S rRNA gene sequences analyses showed that the most closely related species to strain ST22-14T were "Streptococcus vulneris" DM3B3T (99.2%), Streptococcus mitis NCTC 12261T (99.0%), "Streptococcus gwangjuense" ChDC B345T, (99.0%), Streptococcus oralis subsp. dentisani 7747T (99.0%), Streptococcus downii CECT 9732T (99.0%), and Streptococcus infantis ATCC 700779T (98.9%). The genome of strain ST22-14T consists of 2,053,261 bp with a G + C content of 39.4%. Average nucleotide identity values between strain ST22-14T and Streptococcus mitis NCTC 12261T or other five species were from 82.2 to 88.0%. In silico DNA-DNA hybridization of ST22-14T showed an estimated DNA reassociation value of 34.6% with the closest species. The main cellular fatty acids of strain ST22-14T were 16:0, 18:0, 14:0, 18:1ω7c and 18:1ω6c. Based on these results, strain ST22-14T should be classified as a novel species of genus Streptococcus, for which the name Streptococcus taonis sp. nov. is proposed (type strain ST22-14T = NBRC 116002T = BCRC 81402T).

Streptococcus taoyuanensis sp. nov., a Novel Species Isolated from a Patient with Bacteremia.

Streptococcus spp. are important opportunistic pathogen of bacteremia in both immunocompetent and immunosuppressed patients. A streptococcal strain, designated ST2T, was isolated from the blood specimen of a bacteremic patient. Comparative analyses of 16S rRNA, rpoB and groEL gene sequences demonstrated that the novel strain ST2T is a member of the genus Streptococcus. Based on of 16S rRNA gene sequence similarities, the type strains of Streptococcus (S.) parasanguinis (99.2%), S. ilei (98.8%), S. oralis subsp. oralis (97.6%), S. australis (97.5%) and S. sanguinis (97.5%) were the closest neighbours to strain ST2T. The housekeeping gene sequences (rpoB and groEL) similarities of strain ST2T to these closely related type strains were 80.4-97.4%, respectively. The complete draft genome of strain ST2T consisted of 2,155,906 bp with a G + C content of 42.0%. Strain ST2T has an average nucleotide identity (ANI) value of 94.1 and 81.3% with S. parasanguinis ATCC 15912T and S. ilei I-G2T, respectively. The highest in silico DNA-DNA hybridization value with respect to the closest species S. parasanguinis was 55.6%, below the species cut-off of 70% hybridization. The primary cellular fatty acids of strain ST2T were C16:0, C18:1 ω9c, C18:0 and C14:0. Based on biochemical criteria and molecular genetic evidence, it is proposed that strain ST2T be assigned to a new species of the genus Streptococcus as Streptococcus taoyuanensis sp. nov. The type strain of Streptococcus taoyuanensis is ST2T (=NBRC 115928T = BCRC 81374T) as the type strain.

Decline in hospitalization for childhood asthma in different air pollution regions in Taiwan, 2001-2012.

This study aimed to investigate the trends in childhood asthma hospitalization in regions with differing levels of air pollution in Taiwan, 2001-2012. Joinpoint regression was used to identify significant trend changes. The hospitalization rate varied according to gender, geographic region, and age. The incidence of childhood asthma hospitalization decreased from 127.99 to 76.67 (/100,000 population), with an average annual percentage change of around -4.1%; in the Yilan region, the average air pollution concentrations were 19.92 µg/m3, 39.47 µg/m3, 25.99 ppb, 2.19 ppb, and 11.23 ppb for PM2.5, PM10, O3, SO2, and NO2, respectively, which were lower than Taiwan's average values; however, the childhood asthma hospitalization rate was the highest (179.75/100,000 population). The national trend in childhood asthma hospitalization exhibited a significant decrease. The effects of air pollution on childhood asthma were greater in the higher-level air pollution regions, while less association was observed in the lower-level air pollution regions.

The modulation of Th2 immune pathway in the immunosuppressive effect of human umbilical cord mesenchymal stem cells in a murine asthmatic model.

BACKGROUND: Asthma is a chronic airway inflammatory disease that has a high prevalence nowadays, and seeking the means of relieving asthmatic symptoms is now an issue with increased importance. While mesenchymal stem cells have been demonstrated to display immunomodulatory effects, the effect of fetus-type mesenchymal stem cells (MSCs) on asthmatic symptoms in vivo have not been reported to date. METHODS: Female BALB/c mice at 8 weeks of age were sensitized by ovalbumin, and MSCs derived from Wharton's jelly of human umbilical cord mesenchymal stem cells (hUCMSCs) were injected into the asthmatic mice. Airway hyper-responsiveness, lung eosinophil infiltration, cytokine level in splenocyte cultures and serum immunoglobulin level were measured. Enzyme-linked immunosorbent assay was used to determine cytokine and immunoglobulin levels. RESULTS: This current study demonstrated that hUCMSCs attenuated both lung lymphocyte and eosinophil infiltration, and significantly decreased the concentration of Th2 cytokines interleukin-5 in splenocyte cultures. CONCLUSIONS: Human umbilical cord mesenchymal stem cells have the advantage of being easily harvested non-invasively and are capable of rapid proliferation, therefore an ideal material for stem cell-based immune therapies. The current study showed that fetal-type MSCs were able to suppress asthmatic symptoms efficiently, and its immunomodulatory effect resulted primarily from suppressing the Th2 pathway in the animal model. This study suggested that hUCMSCs could be an ideal candidate for cell-based therapies of asthma.

Downregulated CXCL12 expression in mesenchymal stem cells associated with severe aplastic anemia in children.

The mechanisms of idiopathic severe aplastic anemia (SAA) in children are not completely understood. Insufficiency of the bone marrow microenvironment, in which mesenchymal stem cells (MSCs) are an important element, can be a potential factor associated with hematopoietic impairment. In the current study, we studied whether aberrant gene expression could be found in MSCs from children with SAA. Using microarray analysis, two different patterns of global gene expression were detected in the SAA MSCs. Fourteen genes (POLE2, HGF, KIF20A, TK1, IL18R1, KITLG, FGF18, RRM2, TTK, CXCL12, DLG7, TOP2A, NUF2, and TYMS), which are related to DNA synthesis, cytokines, or growth factors, were significantly downregulated. Further, knockdown of gene expression was performed using the small hairpin RNA (shRNA)-containing lentivirus method. We found that knockdown of CXCL12, HGF, IL-18R1, FGF18, or RRM2 expression compelled MSCs from the controls to behave like those from the SAA children, with decreased survival and differentiation potential. Among them, inhibition of CXCL12 gene expression had the most profound effects on the behavior of MSCs. Further experiments regarding re-introduction of the CXCL12 gene could largely recover the survival and differentiation potential in MSCs with inhibition of CXCL12 expression. Our findings suggest that MSCs from children with SAA exhibit aberrant gene expression profiles and downregulation of CXCL12 gene may be associated with alterations in the bone marrow microenvironment.

Umbilical cord-derived mesenchymal stem cells for hematopoietic stem cell transplantation.

Hematopoietic stem cell transplantation (HSCT) is becoming an effective therapeutic modality for a variety of diseases. Mesenchymal stem cells (MSCs) can be used to enhance hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, prevent and treat graft-versus-host disease, and repair tissue damage in patients receiving HSCT. Till now, most MSCs for human clinical application have been derived from bone marrow. However, acquiring bone-marrow-derived MSCs involves an invasive procedure. Umbilical cord is rich with MSCs. Compared to bone-marrow-derived MSCs, umbilical cord-derived MSCs (UCMSCs) are easier to obtain without harm to the donor and can proliferate faster. No severe adverse effects were noted in our previous clinical application of UCMSCs in HSCT. Accordingly, application of UCMSCs in humans appears to be feasible and safe. Further studies are warranted.

High Induction of IL-6 Secretion From hUCMSCs Optimize the Potential of hUCMSCs and TCZ as Therapy for COVID-19-Related ARDS.

Biological and cellular interleukin-6 (IL-6)-related therapies have been used to treat severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure, which prompted further exploration of the role of IL-6 in human umbilical cord mesenchymal stem cell (hUCMSC) therapy. Peripheral blood mononuclear cells (PBMCs) were responders cocultured with hUCMSCs or exogenous IL-6. A PBMC suppression assay was used to analyze the anti-inflammatory effects via MTT assay. The IL-6 concentration in the supernatant was measured using ELISA. The correlation between the anti-inflammatory effect of hUCMSCs and IL-6 levels and the relevant roles of IL-6 and IL-6 mRNA expression was analyzed using the MetaCore functional network constructed from gene microarray data. The location of IL-6 and IL-6 receptor (IL-6R) expression was further evaluated. We reported that hUCMSCs did not initially exert any inhibitory effect on PHA-stimulated proliferation; however, a potent inhibitory effect on PHA-stimulated proliferation was observed, and the IL-6 concentration reached approximately 1000 ng/mL after 72 hours. Exogenous 1000 ng/mL IL-6 inhibited PHA-stimulated inflammation but less so than hUCMSCs. The inhibitory effects of hUCMSCs on PHA-stimulated PBMCs disappeared after adding an IL-6 neutralizing antibody or pretreatment with tocilizumab (TCZ), an IL-6R antagonist. hUCMSCs exert excellent anti-inflammatory effects by inducing higher IL-6 levels, which is different from TCZ. High concentration of IL-6 cytokine secretion plays an important role in the anti-inflammatory effect of hUCMSC therapy. Initial hUCMSC therapy, followed by TCZ, seems to optimize the therapeutic potential to treat COVID-19-related acute respiratory distress syndrome (ARDS).

Poor potential of proliferation and differentiation in bone marrow mesenchymal stem cells derived from children with severe aplastic anemia.

The pathogenesis of severe aplastic anemia (SAA) has not been completely understood, and insufficiency of the hematopoietic microenvironment can be an important factor. Here, we compared the basic properties of mesenchymal stem cells (MSCs), a major component of bone marrow microenvironment, from five SAA children with those of MSCs from five controls. Although MSCs from SAA children and controls were similar in morphology and immunophenotypic profile, SAA MSCs had slower expansion rate and smaller cumulative population doubling (1.83 +/- 1.21 vs 3.36 +/- 0.87; p = 0.046), indicating lower proliferative capacity. After osteogenic induction, SAA MSCs showed lower alkaline phosphatase activity (optical density, 1.46 +/- 0.04 vs 2.27 +/- 0.32; p = 0.013), less intense von Kossa staining, and lower gene expression of core binding factor alpha1 (0.0015 +/- 0.0005 vs 0.0056 +/- 0.0017; p = 0.013). Following adipogenic induction, SAA MSCs showed less intense Oil red O staining (optical density, 0.86 +/- 0.22 vs 1.73 +/- 0.42; p = 0.013) and lower lipoprotein lipase expression (0.0105 +/- 0.0074 vs 0.0527 +/- 0.0254; p = 0.013). These findings provided evidence that defects in bone marrow MSCs of SAA children do exist.

Sequential evaluation of serum monocyte chemotactic protein 1 among asymptomatic state and acute exacerbation and remission of asthma in children.

BACKGROUND: Monocyte chemotactic protein 1 (MCP-1) plays an important role in various immune and allergic disorders since it is a potent chemo-attractant for inflammatory cells, such as eosinophils, memory T cells, and monocytes. OBJECTIVE: To investigate serum MCP-1 during asymptomatic state and acute attacks of bronchial asthma. METHODS: In this longitudinal cohort design study, sequential serum levels of MCP-1 were measured by a sandwich enzyme-linked immunosorbent assay (ELISA). Twenty-four asthma patients' MCP-1 levels were examined at 5 time points: during the asymptomatic phase, in an acute wheezing episode, and at 1 week, 1 month, and 2 months after acute asthma attack. Fifteen children without asthma were enrolled as control. RESULTS: During the asymptomatic phase of asthma, serum MCP-1 levels were significantly higher than that of normal controls (329.57 +/- 99.20 pg/ml vs. 213.63 +/- 77.29 pg/ml, p = 0.001). In comparison with the asymptomatic phase, the serum MCP-1 levels during the acute asthma attack were significantly higher (682.88 +/- 88.45 pg/ml vs. 329.57 +/- 99.20 pg/ml, p < 0.001). After treatment of acute asthma exacerbation, all of the serum MCP-1 levels declined within 1 week, but were still higher than control 2 months later. CONCLUSION: In asthma patients, the consistently elevated serum levels of MCP-1 suggest its role in the pathogenesis of bronchial asthma - not only in the chronic inflammatory processes, but also in acute asthma attack exacerbation. These findings suggest a possible role for MCP-1 in the pathogenesis of asthma and a potential role for its use in anti-asthma treatment in the future.

The Short-Term Effects of Ambient Air Pollutants on Childhood Asthma Hospitalization in Taiwan: A National Study.

This investigation determined the effects of air pollution on childhood asthma hospitalization in regions with differing air pollution levels in Taiwan over a long time period. Data of childhood hospital admissions for asthma in patients aged 0⁻18 years and air quality in eight regions for the period 2001⁻2012 in Taiwan were collected. Poisson generalized linear regression analysis was employed to identify the relative risks of hospitalization due to asthma in children associated with exposure to varying levels of air pollutants with a change in the interquartile range after adjusting for temperature and relative humidity. Particulate matter ≤2.5 µm (PM2.5), particulate matter ≤10 µm (PM10), ozone (O3), sulfur dioxide (SO2), and nitrogen dioxide (NO2), were positively associated with childhood asthma hospitalization, while O3 was negatively associated with childhood asthma hospitalization. SO2 was identified as the most significant risk factor. The relative risks for asthma hospitalization associated with air pollutants were higher among children aged 0⁻5 years than aged 6⁻18 years and were higher among males than females. The effects of air pollution on childhood asthma were greater in the higher-level air pollution regions, while no association was observed in the lower-level air pollution regions. These findings may prove important for policymakers involved in implementing policies to reduce air pollution.

Therapeutic effects of a single injection of human umbilical mesenchymal stem cells on acute and chronic colitis in mice.

Multiple injections of bone marrow mesenchymal stem cells (BMMSCs) have been used for treatment of chronic colitis in mice. We aimed to report the therapeutic effects of a single injection of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute and chronic colitis. Male C57BL/6JNarl mice were divided into control, phosphate-buffered saline (PBS), and hUCMSCs treated groups, respectively. Acute and chronic colitis were induced in the mice (except controls) using 3% dextran sulfate sodium (DSS). The mice in the hUCMSCs group underwent a single injection of hUCMSCs. The disease activity index (DAI), colon length, histology, colon inflammation score, in vivo stem cells images, and blood cytokine levels were recorded. The DAI was significantly higher in the hUCMSCs group than in the control group and lower than in the PBS group on all days. The colon length was significantly longer and the colon inflammation score was significantly lower in the hUCMSCs group than in the PBS group on days 8 and 25. IL17A, Gro-α, MIP-1α, MIP-2, and eotaxin were significantly lower in the hUCMSCs group than in the PBS group on days 8 and 25. Single-injection hUCMSCs improved DSS-induced acute colitis and decreased progression of acute colitis to chronic colitis.

Application of a Time-Stratified Case-Crossover Design to Explore the Effects of Air Pollution and Season on Childhood Asthma Hospitalization in Cities of Differing Urban Patterns: Big Data Analytics of Government Open Data.

Few studies have assessed the lagged effects of levels of different urban city air pollutants and seasons on asthma hospitalization in children. This study used big data analysis to explore the effects of daily changes in air pollution and season on childhood asthma hospitalization from 2001 to 2010 in Taipei and Kaohsiung City, Taiwan. A time-stratified case-crossover study and conditional logistic regression analysis were employed to identify associations between the risk of hospitalization due to asthma in children and the levels of air pollutants (PM2.5, PM10, O3, SO2, and NO2) in the days preceding hospitalization. During the study period, 2900 children in Taipei and 1337 in Kaohsiung aged ≤15 years were hospitalized due to asthma for the first time. The results indicated that the levels of air pollutants were significantly associated with the risk of asthma hospitalization in children, and seasonal effects were observed. High levels of air pollution in Kaohsiung had greater effects than in Taipei after adjusting for seasonal variation. The most important factor was O3 in spring in Taipei. In children aged 0-6 years, asthma was associated with O3 in Taipei and SO2 in Kaohsiung, after controlling for the daily mean temperature and relative humidity.

Septic arthritis in patients with systemic lupus erythematosus: salmonella and nonsalmonella infections compared.

OBJECTIVES: To assess the clinical characteristics and outcome of systemic lupus erythematosus (SLE) with septic arthritis. METHODS: In this 20-year retrospective study, we reviewed the charts of SLE patients with septic arthritis confirmed by synovial fluid analysis and culture. To identify risk factors for septic arthritis, data of SLE patients with septic arthritis were compared with data of 100 hospitalized SLE patients without septic arthritis. RESULTS: There were 10,732 inpatient records of 3,127 SLE patients; 29 SLE patients had septic arthritis. Their ages ranged from 14 to 68 years (mean, 35.1 +/- 14.1 years). The mean SLE duration before septic arthritis onset was 30.6 months. All patients received corticosteroids; 93% had active disease (SLEDAI > or = 4). Compared with controls, avascular necrosis (AVN) of the femoral head was the most common predisposing articular disease (Odds ratio, 3.799;CI, 1.59 to 9.05). Of the 29 patients, 17 (59%) had salmonella infections and 12 (41%) had other infections. Salmonella-infected patients were younger (28.7 +/- 10.4 years) than those with nonsalmonella infections (44.1 +/- 14.0 years; P = 0.002). The hip was the most commonly affected joint, especially in the salmonella group, followed by the knees and ankles. Salmonella-infected patients were more prone to oligo-articular septic arthritis. The overall mortality rate was 10%. CONCLUSIONS: Salmonella enteritidis B is the most common pathogen causing septic arthritis in younger SLE patients. Septic arthritis tended to be oligo-articular and involve the hip joint. AVN of the femoral head was the most common predisposing articular disease. Once septic arthritis is suspected, culture specimens should be collected and appropriate antibiotics given immediately.

The role of mesenchymal stem cells in hematopoietic stem cell transplantation: from bench to bedsides.

Mesenchymal stem cells (MSCs) have been shown to be effective in the management of graft-versus-host disease (GVHD) due to their immunomodulatory effects. In addition to prevention and treatment of GVHD, many studies have demonstrated that MSCs can promote hematopoietic engraftment, accelerate lymphocyte recovery, reduce the risk of graft failure, and repair tissue damage in patients receiving hematopoietic stem cell transplantation (HSCT). Bone marrow (BM) has been considered as the traditional source of MSCs, and most of the knowledge concerning MSCs comes from BM studies. However, BM-derived MSCs have several limitations for their clinical application. Fetal-type MSCs can be isolated easier and proliferate faster in vitro as well as possessing a lower immunogenicity. Therefore, fetal-type MSCs, such as umbilical cord-derived MSCs, represent an excellent alternative source of MSCs. MSCs play multiple important roles in HSCT. Nevertheless, several issues regarding their clinical application remain to be discussed, including the safety of use in humans, the available sources and the convenience of obtaining MSCs, the quality control of in vitro-cultured MSCs and the appropriate cell passages, the optimum cell dose, and the optimum number of infusions. Furthermore, it is important to evaluate whether the rates of cancer relapse and infections increase when using MSCs for GVHD. There are still many questions regarding the clinical application of MSCs to HSCT that need to be answered, and further studies are warranted.

The comparison of interleukin 6-associated immunosuppressive effects of human ESCs, fetal-type MSCs, and adult-type MSCs.

BACKGROUND: Although human embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs) from various sources display immunomodulatory effects, direct comparisons among these classes of stem cells have not been reported. METHODS: Peripheral blood mononuclear cell suppression assays and carboxyfluorescein diacetate succinimidyl ester assays were used to assess the immunosuppressive effects of stem cells. Gene expression was measured using DNA microarrays. Enzyme-linked immunosorbent assays were used to determine interleukin (IL)-6 levels. RESULTS: We found that fetal-type MSCs proliferated significantly faster than adult-type MSCs. Compared with ESCs grown on feeder cells, ESCs grown in feeder cell-free conditions exhibited decreased immunosuppressive effects. The suppressive effects of ESCs were significantly stronger than those of MSCs, and the suppressive effects of fetal-type MSCs were significantly stronger than those of adult-type MSCs at each tested dose level. Analysis of gene expression by microarray and MetaCore pathway mapping revealed changes in eight different immune response pathways; we observed that IL-6 gene expression was highly significantly involved in all eight pathways. Significantly higher IL-6 elevation ratios (IL-6after:IL-6before) were found in ESCs compared with fetal-type MSCs, and these were also found in fetal-type MSCs compared with adult-type MSCs. Furthermore, IL-6 levels were found to correlate with cell dosages of MSCs and the suppressive effects. CONCLUSIONS: The ease of obtaining fetal-type MSCs and their rapid proliferation make these cells ideal candidates for cell-based therapies, especially for diseases associated with immune responses, given the immunosuppressive effects of these cells. IL-6 might play an important role in the immunosuppressive effects of various stem cells.

Effective treatment of severe steroid-resistant acute graft-versus-host disease with umbilical cord-derived mesenchymal stem cells.

BACKGROUND: Severe steroid-resistant acute graft-versus-host disease (aGVHD) is associated with high mortality. Bone marrow-derived mesenchymal stem cells (BMMSC) have been found to be immunosuppressive, and intravenous infusion of BMMSC is an effective therapy for steroid-resistant aGVHD. However, acquiring BMMSC requires an invasive procedure. METHODS: We compared umbilical cord-derived mesenchymal stem cells (UCMSC) and BMMSC for morphology, surface markers expression, differentiation, proliferative potential, and their suppressive effects on peripheral blood mononuclear cell proliferation. After institutional review board approved, we intravenously infused ex vivo expanded third-party UCMSC into two patients with severe steroid-resistant aGVHD. Adverse effects and patient responses of UCMSC were monitored. All procedures for UCMSC processing complied with current good tissue practice requirements. RESULTS: We found that UCMSC had superior proliferative potential and more suppressive effects on peripheral blood mononuclear cell proliferation compared with BMMSC. The aGVHD improved dramatically after each of four infusions of UCMSC into the two patients. No adverse effects were noted. Both patients are doing well now. CONCLUSIONS. Considering that acquiring UCMSC is noninvasive, these cells would appear to be the ideal candidates for clinical cell-based therapies. This is the first report of UCMSC in a human clinical application, and this procedure seems both feasible and safe. These findings suggested that UCMSC were effective for treating aGVHD.

Ding Chuan Tang, a Chinese herb decoction, could improve airway hyper-responsiveness in stabilized asthmatic children: a randomized, double-blind clinical trial.

Traditional Chinese medicine has a long history of application in the treatment of bronchial asthma. Solid scientific evidence, however, is not available despite its widespread use among patients worldwide and in Taiwan. To assess the effect of Ding Chuan Tang (DCT) in airway hyper-responsiveness (AHR) on asthmatic children via randomized, double blind, placebo-controlled clinical trial. This study enrolled children who were aged 8-15 and diagnosed as mild to moderate persistent asthma patients. They were randomly allocated to receive 6.0 g DCT or placebo daily for 12 wk. Self-recorded daily symptom scores, medication scores, and morning and evening peak expiratory flow rates were returned at the monthly clinic. Pulmonary function test, methacholine challenge test, and serum inflammatory mediators were measured before and at the end of the trial. Fifty-two asthmatic children completed the clinical study. Twenty-eight patients were assigned to the treatment group and 24 to the placebo group. At the end of the treatment period, AHR determined by log PC(20) was significantly improved in the DCT group (0.51 +/- 1.05 mg/ml vs. 0.26 +/- 0.84 mg/ml, p = 0.034). The total clinical and medication reduced parameters showed improvement in the DCT group (p = 0.004). The AHR, symptom and medication scores in children with persistent asthma were significantly improved with DCT treat for 12 wk. The results suggested more stable airways achieved with such an add-on complementary therapy.

RANTES and monocyte chemoattractant protein 1 as sensitive markers of disease activity in patients with juvenile rheumatoid arthritis: a six-year longitudinal study.

OBJECTIVE: To longitudinally investigate serum and synovial fluid (SF) levels of RANTES and monocyte chemoattractant protein 1 (MCP-1) as well as in vitro migration of mononuclear cells toward SF in patients with juvenile rheumatoid arthritis (JRA). METHODS: Serum and SF levels of RANTES and MCP-1 were determined by enzyme-linked immunosorbent assay. Chemotaxis was performed using the modified Boyden chamber method. RESULTS: Serum RANTES levels were significantly increased in all onset types of JRA, with the highest levels present in systemic-onset JRA. Serum MCP-1 levels were significantly elevated in patients with systemic-onset JRA and were associated with current systemic features. Although serum levels of RANTES and MCP-1 decreased significantly after treatment, RANTES and MCP-1 levels during disease remission were still significantly higher in JRA patients than in controls. A relationship was found between serum RANTES levels during remission and the duration of clinical remission, with low levels being associated with prolonged clinical remission and high levels with shorter clinical remission. Serum RANTES levels correlated with C-reactive protein concentrations, hemoglobin values, white blood cell (WBC) counts, and platelet counts, whereas serum MCP-1 levels correlated with WBC counts and serum ferritin levels. Levels of RANTES and MCP-1 in SF were elevated as compared with levels in serum. SF chemotactic activity for mononuclear leukocytes was significantly inhibited by either anti-RANTES or anti-MCP-1 antibody. CONCLUSION: RANTES is a key molecule in the pathogenesis of all onset groups of JRA, whereas MCP-1 is particularly important in systemic-onset JRA. Serum levels of these CC chemokines represent more highly sensitive markers of disease activity than conventional markers of inflammation.

Cutaneous lymphocytic vasculitis as the presenting feature of acute lymphoblastic leukemia.

The authors describe a patient with precursor B-cell acute lymphoblastic leukemia who presented with a 3-week history of indurated or ulcerative, purpuric lesions distributed mainly on her legs. A skin biopsy demonstrated a T-cell-mediated lymphocytic vasculitis. After the patient started chemotherapy, the skin lesions abated but she became febrile and a blood culture revealed cryptococci. The cryptococcal infection was successfully treated first with amphotericin B and later with fluconazole. The relationship between lymphocytic vasculitis and acute lymphoblastic leukemia may be an example of paraneoplastic association because both conditions seem to have appeared at about the same time, and both followed a parallel course. Lymphocytic vasculitis may also reflect a new manifestation of host-leukemia interaction.