A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test

The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976–1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5–95 years with 45.5% over 60 years. The referring specialities were Gastroenterology (47.6%), Haematology (11.3%), Paediatries (2.1%) and all others (39.9%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B₁₂ malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio 1.3 and 127 (73.8%) a ratio 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%).     

Effects of long working hours and the night shift on severe sleepiness among workers with 12‐hour shift systems for 5 to 7 consecutive days in the automobile factories of Korea

We investigated the effects of 12‐hour shift work for five to seven consecutive days and overtime on the prevalence of severe sleepiness in the automobile industry in Korea. [Correction added after online publication 28 Nov: Opening sentence of the summary has been rephrased for better clarity.] A total of 288 randomly selected male workers from two automobile factories were selected and investigated using questionnaires and sleep‐wake diaries in South Korea. The prevalence of severe sleepiness at work [i.e. Karolinska Sleepiness Scale (KSS) score of 7 or higher] was modeled using marginal logistic regression and included theoretical risk factors related to working hours and potential confounding factors related to socio‐economic status, work demands, and health behaviors. Factors related to working hours increased the risk for severe sleepiness at the end of the shift in the following order: the night shift [odds ratio (OR): 4.7; 95% confidence interval (CI): 3.6–6.0)], daily overtime (OR: 2.2; 95% CI: 1.7–2.9), weekly overtime (OR: 1.6; 95% CI: 1.0–2.6), and night overtime (OR: 1.6; 95% CI: 0.8–3.0). Long working hours and shift work had a significant interactive effect for severe sleepiness at work. Night shift workers who worked for 12 h or more a day were exposed to a risk of severe sleepiness that was 7.5 times greater than day shift workers who worked less than 11 h. Night shifts and long working hours were the main risk factors for severe sleepiness among automobile factory workers in Korea. Night shifts and long working hours have a high degree of interactive effects resulting in severe sleepiness at work, which highlight the need for immediate measures to address these characteristics among South Korean labor force patterns.     

人白细胞介素12在哺乳动物细胞中的稳定表达及其生物活性的研究

目的采用遗传基因工程方法获得具有生物活性的人白细胞介素12,探索其治疗肿瘤和慢性肝炎的可行性。方法采用已克隆的国人IL-12基因序列,利用内部核糖体切入位点(IRES)完成IL-12P35、P40双亚基共表达载体的构建,通过转染CHODHFR缺陷细胞,双抗夹心ELISA法筛选阳性克隆,MTX加压扩增,PCR检测其基因整合,T淋巴细胞增殖和诱生γ干扰素实验检测其生物活性。结果获得了稳定高效表达人IL-12的工程细胞系,表达产物为70×103左右的糖蛋白。结论本研究得到的基因重组人IL-12具有良好的生物活性,有强的诱导产生γ干扰素的能力和诱导活化T淋巴细胞增殖能力。     

Osteopontin affects the persistence of beta-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms

Osteopontin (OPN) plays a pivotal role in various immune responses and inflammatory diseases. OPN is expressed in various granulomatous diseases; however, the cellular and molecular role of OPN in these diseases is not well known. We analyzed the role of OPN in a beta-glucan-induced hepatic granuloma model. First, we found that neither OPN deficiency nor overexpression of OPN affected the number and the size of hepatic granulomas at day 7, indicating that OPN is not involved in the formation of hepatic granulomas at the early stages. Importantly, OPN did not influence the liver tissue damage as defined by alanine aminotransferase and aspartate aminotransferase levels at early stages. Second, OPN deficiency resulted in the reduction of IL-12 and IFN-gamma production at early stages. Third, at late stages, OPN deficiency resulted in a decrease in the number and size of hepatic granulomas, and a reduction of liver tissue injury. This was due to the reduction of the cellular recruitment including macrophages, CD4 T cells and dendritic cells into the liver, and the reduction of tumor necrosis factor (TNF)-alpha production in the liver. In contrast, overexpression of OPN resulted in the persistence of granuloma formation. These data suggest that OPN affects the persistence of hepatic granuloma formation. Our results indicate that OPN up-regulates the production of IL-12 and IFN-gamma within the granulomas at early stages, and OPN has an additional role in the regulation of cellular recruitment and TNF-alpha production at late stages that determine the severity of liver tissue injury.     

Differential effects of interleukin 12 and interleukin 10 on superantigen-induced expression of cutaneous lymphocyte-associated antigen (CLA) and alphaEbeta7 integrin (CD103) by CD8+ T cells

At both cutaneous and mucosal sites, interleukin (IL)-10, IL-12 and transforming growth factor (TGF)-beta are important regulators of chronic inflammatory disease, where cutaneous lymphocyte-associated antigen (CLA) and alphaE integrin (CD103) may be expressed. Stimulation with streptococcal pyrogenic exotoxin C (SpeC) increased the expression of CD103 by CD8+ but not CD4+ T cells. While adding IL-12 augmented the expression of CLA, superantigen-induced expression of CD103 was markedly suppressed by IL-12, which could be reversed by TGF-beta. Antibodies against TGF-beta inhibited, and a combination of anti-TGF-beta and IL-12 completely abrogated the induced CD103 expression. IL-10 strongly decreased the frequency of CLA+ and although not increasing the frequency of CD103+CD8+ T cells, the amount of CD103 expressed per cell was markedly increased. Thus, the expression of CLA and CD103 may be antagonistically regulated by IL-10 and IL-12 and the balance between these cytokines could influence the T cell migration of inflammatory cells into epithelial tissues.     

Nasal congestion as a side effect of cromolyn sodium

Cromolyn sodium, a recently introduced antiasthmatic medication, is known occasionally to produce maculopapular and urticarial rashes, and increased bronchospasm. A patient is reported with a previously unpublished side effect of this medication, i.e., severe nasal congestion.     

心脑疾病对同步十二导联心电图多重分形谱的影响

对心脑疾病人群的同步十二导联ECG(心电图)进行多重分形特性分析,发现不同导联的多重分形曲线互不重叠。计算其十二导联平均的多重分形奇异强度分布范围以及分布范围的十二个导联间的离散特性,发现不同人群中存在互为交叉而有明显不同的结果。用十二导联多重分形Δα的平均值Δα及其离散度δα(取Δα的标准差)两个参量来描述其多重分形谱特征。发现健康人与心脏病人Δα接近,但δα相差较大;健康人与脑损伤患者δα接近,但Δα相差较大。预示着多重分形特性受到神经自律和心脏组织结构的自谐特性的双重控制,特征参数Δα与神经控制相对应,δΔ与心脏组织结构自谐特性的各向异性相对应。     

Heligmosomoides polygyrus inhibits established colitis in IL-10-deficient mice

Inflammatory bowel disease (IBD) is prevalent in industrialized countries, but rare in less-developed countries. Helminths, common in less-developed countries, may induce immunoregulatory circuits protective against IBD. IL-10(-/-) mice given piroxicam develop severe and persistent colitis. Lamina propria mononuclear cells from colitic IL-10(-/-) mice released IFN-gamma and IL-12. The ongoing piroxicam-induced colitis could be partially blocked with anti-IL-12 monoclonal antibody suggesting that the inflammation was at least partly IL-12 dependent. Colonization of piroxicam-treated colitic IL-10(-/-) mice with Heligmosomoides polygyrus (an intestinal helminth) suppressed established inflammation and inhibited mucosal IL-12 and IFN-gamma production. H. polygyrus augmented mucosal IL-13, but not IL-4 or IL-5 production. Transfer of mesenteric lymph node (MLN) T cells from IL-10(-/-) animals harboring H. polygyrus into colitic IL-10(-/-) recipients inhibited colitis. MLN T cells from worm-free mice did not. Foxp3 (scurfin) drives regulatory T cell function. H. polygyrus enhanced Foxp3 mRNA expression in MLN T cells that had regulatory activity. This suggests that H. polygyrus inhibits ongoing IL-10(-/-) colitis in part through blocking mucosal Th1 cytokine production. Resolution of inflammation is associated with increased IL-13 production and can be adoptively transferred by MLN T cells.     

Increased circulating interleukin-12 (IL-12) p40 in pulmonary sarcoidosis

In sarcoidosis, a T helper 1 (Th1) response is an essential event and the up-regulation of interleukin-12 (IL-12) has been detected in affected disease sites. In order to investigate the clinical usefulness of circulating IL-12, we measured the serum concentrations of IL-12 by ELISA and performed immunohistochemistry using specific MoAbs for IL-12 in the lungs and scalene lymph nodes of patients with sarcoidosis. The serum concentration of IL-12 p40 was detectable in all 45 patients with pulmonary sarcoidosis and 18 normal controls, whereas that of IL-12 p70 was undetectable. The serum concentrations of IL-12 p40 in pulmonary sarcoidosis were significantly higher than those of the normal controls, especially in cases with abnormal intrathoracic findings detected by chest roentogenogram. The serum concentrations of interferon-gamma (IFN-gamma) also increased compared with those of normal controls and there was a significant positive correlation between the serum concentrations of IL-12 p40 and IFN-gamma. Furthermore, serum angiotensin-converting enzyme (ACE) and lysozyme, which are known to be useful markers for disease activity in sarcoidosis, correlated well with the serum concentrations of IL-12 p40. The positive 67Ga scan group (for lung field) had significantly elevated serum IL-12 p40 levels compared with those of the negative group. No bioactivity of IL-12 p70 was detected in three sarcoid cases sera by using the IL-12 responsive cell line. Finally, the immunohistochemical approach revealed that IL-12 p40 was expressed in the epithelioid cells and macrophages of sarcoid lungs and lymph nodes. We concluded that the production of IL-12 p40 was far greater in the sera and we have demonstrated this to be a useful clinical marker for disease activity and the Th1 response in pulmonary sarcoidosis.