Plasma cells induce apoptosis of pre-B cells by interacting with bone marrow stromal cells

By using two-color phenotypic analysis with fluorescein isothiocyanate- anti-CD38 and phycoerythrin-anti-CD19 antibodies, we found that pre-B cells (CD38+CD19+) signifcantly decreased depending on the number of plasma cells (CD38++CD19+) in the bone marrow (BM) in the cases with BM plasmacytosis, such as myelomas and even polyclonal gammopathy. To clarify how plasma cells suppress survival of pre-B cells, we examined the effect of plasma cells on the survival of pre-B cells with or without BM-derived stromal cells in vitro. Pre-B cells alone rapidly entered apoptosis, but interleukin-7 (IL-7), a BM stromal cell line (KM- 102), or culture supernatants of KM-102 cells could support pre-B cell survival. On the other hand, inhibitory factors such as transforming growth factor-beta1 (TGF-beta1) and macrophage inflammatory protein- 1beta (MIP-1beta) could suppress survival of pre-B cells even in the presence of IL-7. Plasma cells alone could not suppress survival of pre- B cells in the presence of IL-7, but coculture of plasma cells with KM- 102 cells or primary BM stromal cells induced apoptosis of pre-B cells. Supernatants of coculture with KM-102 and myeloma cell lines (KMS-5) also could suppress survival of pre-B cells. Furthermore, we examined the expression of IL-7, TGF-beta1, and MIP-1beta mRNA in KM-102 cells and primary stromal cells cocultured with myeloma cell lines (KMS-5). In these cells, IL-7 mRNA was downregulated, but the expression of TGF- beta1 and MIP-1beta mRNA was augmented. Therefore, these results suggest that BM-derived stromal cells attached to plasma (myeloma) cells were modulated to secrete lesser levels of supporting factor (IL- 7) and higher levels of inhibitory factors (TGF-beta1 and MIP-1beta) for pre-B cell survival, which could explain why the increased number of plasma (myeloma) cells induced suppression of pre-B cells in the BM. This phenomenon may represent a feedback loop between pre-B cells and plasma cells via BM stromal cells in the BM.     

Tracking of Blood Pressure Among Adolescents and Young Adults in an Urban Slum of Puducherry

Background:

Early diagnosis of hypertension (HT) is an important strategy in its control. Tracking of blood pressure (BP) has been found useful in identifying persons with potential HT, particularly in youngsters. A cohort of 756 subjects (with baseline information as a cross-sectional study in 2002) was followed up in 2006 to comment on the distribution of BP and its attributes.

Objectives:

To track BP distribution in a cohort of adolescents and young adults, and assess the persistence of high/low normotensives; to measure the incidence of HT and study the relationship of BP with age, sex, socioeconomic status, BMI, physical exercise, salt intake, smoking and alcohol consumption.

Materials and Methods:

The baseline study cohort (2002) of 756 subjects (19-24 years) in urban field area of Department of Preventive and Social Medicine, JIPMER, was followed up between May and November 2006 by house visits for measurement of sociodemographic variables, anthropometry, salt intake, physical activity and BP.

Results:

A total of 555 subjects from the 2002 cohort were contacted (73.4%), in that 54.5% subjects who were below 5^th percentile, 93.6% subjects between 5^th and 95^th percentiles and 72% of those above 95^th percentile previously persisted in the same cut-offs for systolic blood pressure (SBP). The corresponding figures for diastolic blood pressure (DBP) were 46.2, 92.2 and 74.1%, respectively. Shift from one cut-off to another was not significant for both SBP and DBP, proving the tracking phenomenon. Annual incidence of HT was 9.8/1000. Baseline BP was the significant predictor of current BP for the entire cohort; BMI and salt intake were significant predictors only in certain sections of the study cohort.

Conclusions:

Early diagnosis of hypertension even among adolescents/young adults is an important preventive measure, as tracking exists in the population.     

ANTIBODIES TO SACCHAROMYCES CEREVISIAE and ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODIES IN INFLAMMATORY BOWEL DISEASE: ASSESSMENT and RELEVANCE IN AN AUSTRALIAN POPULATION USING TWO DIFFERENT ASCA ASSAY KITS

A number of North American and European studies have elucidated a relationship between antibodies to the yeast Saccharomyces cerevisiae (ASCA) and Crohn's disease (CD).
Aims  (1) To ascertain whether this relationship is relevant to Australian patients; (2) To compare the results with two different commercial ASCA kits; (3) To examine the usefulness of this test in combination with perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) for distinguishing Crohn's disease from ulcerative colitis (UC).
Methods  Serum samples were obtained from 28 patients with CD, 27 patients with UC and 22 non-IBD patients presenting for investigation of other gastroenterological illnesses. ASCA IgG and IgA were determined by enzyme immunoassay using the two test kits. pANCA was detected by indirect immunofluorescence.
Results  Using the Medizym test kit, the presence of either IgG or IgA ASCA was 50% sensitive and 93% specific for CD. The QUANTA Lite kit yielded a higher sensitivity of 79% but specificity of 74%. The sensitivity of pANCA for UC was 48% but was 100% specific. Used in combination, ASCA+ve/pANCA–ve was only 50% sensitive but 100% specific for CD using the Medizym kit compared with 79% sensitivity and 93% specificity using QUANTA Lite. The combination of ASCA–ve/pANCA+ve was 41% sensitive and 100% specific for ulcerative colitis using the Medizym kit compared with 30% sensitive and 100% specific using QUANTA Lite.
Conclusions  At least 50% of Australian patients with CD have ASCA detectable in serum, confirming the results of overseas studies. Sensitivity was greater with the QUANTA Lite kit whereas the Medizym kit was slightly more specific. ASCA may aid in the diagnosis of CD. When used in combination with pANCA it may also help distinguish CD from UC in difficult cases.     

Treatment of water for dialysis ‐ A European survey

The EDTNA/ERCA survey of the treatment of water for dialysis was the third project organised through the Collaborative Research Programme (CRP). Data was collected from 69 haemodialysis facilities in 14 countries. Water quality in European dialysis units was mainly self‐regulated. The majority of centres aimed to meet the requirements of the European Pharmacopoeia, but only 50% carried out tests to check compliance. All facilities used reverse osmosis to treat water for dialysis, most also used softening and carbon adsorption. There was a wide variation in policies for the maintenance of carbon filters, and for the control and monitoring of contamination in the distribution system. Endotoxin tests carried out in 27 facilities showed that higher levels of contamination are associated with systems that are infrequently disinfected, and also with older system designs. The survey indicated that guidelines for water treatment are urgently needed. EDTNA/ERCA guidelines for microbiological monitoring are now being drafted, additional guidelines are under consideration.     

The role of adiponectin for immune cell function in metabolic diseases

Adiponectin, as an indispensable regulator of the immune system, is the most abundant adipokine and is mainly produced by white adipose tissue. Adiponectin mediates the positive effects on systemic metabolism by regulating associated downstream signalling pathways; however, accumulating evidence shows that adiponectin plays an important role in regulating the function of innate and adaptive immune cells in the development of obesity and its related diseases. In this review, we focus on the biological function of adiponectin in regulating innate and adaptive immunity and outline the key role of adiponectin in various metabolic diseases, which will highlight a potential direction for adiponectin-based therapeutic interventions for metabolic diseases.     

Gut microbiota changes in patients with hypertension: A systematic review and meta-analysis

Hypertension is a major public health issue worldwide. The imbalance of gut microbiota is thought to play an important role in the pathogenesis of hypertension. The authors conducted the systematic review and meta-analysis to clarify the relationship between gut microbiota and hypertension through conducting an electronic search in six databases. Our meta-analysis included 19 studies and the results showed that compared with healthy controls, Shannon significantly decreased in hypertension [SMD = −0.13, 95%CI (−0.22, −0.04), p = .007]; however, Simpson [SMD = −0.01, 95%CI (−0.14, 0.12), p = .87], ACE [SMD = 0.18, 95%CI (−0.06, 0.43), p = .14], and Chao1 [SMD = 0.11, 95%CI (−0.01, 0.23), p = .08] did not differ significantly between hypertension and healthy controls. The F/B ratio significantly increased in hypertension [SMD = 0.84, 95%CI (0.10, 1.58), p = .03]. In addition, Shannon index was negatively correlated with hypertension [r = −0.12, 95%CI (−0.19, −0.05)], but had no significant correlation with SBP [r = 0.10, 95%CI (−0.19, 0.37)] and DBP [r = −0.39, 95%CI (−0.73, 0.12)]. At the phylum level, the relative abundance of Firmicutes [SMD = −0.01, 95%CI (−0.37, 0.34), p = .94], Bacteroidetes [SMD = −0.15, 95%CI (−0.44, 0.14), p = .30], Proteobacteria [SMD = 0.25, 95%CI (−0.01, 0.51), p = .06], and Actinobacteria [SMD = 0.21, 95%CI (−0.11, 0.53), p = .21] did not differ significantly between hypertension and healthy controls. At the genus level, compared with healthy controls, the relative abundance of Faecalibacterium decreased significantly [SMD = −0.16, 95%CI (−0.28, −0.04), p = .01], while the Streptococcus [SMD = 0.20, 95%CI (0.08, 0.32), p = .001] and Enterococcus [SMD = 0.20, 95%CI (0.08, 0.33), p = .002] significantly increased in hypertension. Available evidence suggests that hypertensive patients may have an imbalance of gut microbiota. However, it still needs further validation by large sample size studies of high quality.     

QUADAS的制定:用于系统评价中评价诊断性研究质量的工具

背景在以系统评价为基石的循证医学时代,需要有恰当的质量评价工具。对诊断性研究的评价目前尚缺乏系统开发且经过验证的评价工具。本研究的目的是采用共识决策法整合经验证据和专家意见,制定在系统评价时用于评价原始诊断性研究质量的工具。方法按照循证原则,我们在之前发表的3篇诊断性研究文献的综述的基础上,初选出一些条目形成列表,然后通过Delphi流程逐步调整列表,形成质量评价工具。参与Delphi流程的都是诊断性研究领域的专家。结果共有9位诊断学领域的专家参与Delphi流程。经过4轮Delphi流程后,专家们对哪些条目应纳入评价工具达成共识,我们把这个评价工具命名为QUADAS。纳入条目从最初的28个减少到14个,涵盖了疾病谱、金标准、疾病进展偏倚(disease progression bias)、证实偏倚(verification bias)、评价偏倚、临床评价偏倚、合并偏倚、试验的实施、病例退出以及不确定结果。QUADAS工具中的每个条目都配有评分细则。结论本研究项目开发出了用于诊断性试验系统评价的循证质量评价工具。下一步工作是确定其适用性和有效性。