Microscopic Haematuria as a Predictor of Urological Diseases among Steel Workers

A cohort of 501 workers in a steel mill in Ontario, Canada wasfollowed up from 1974 to 1986 for 13 years. Results indicatethat the 13-year cumulative incidence of urological diseasesamong workers who had a positive urinalysis result of microscopichaematuria at the beginning of the follow-up period (1974) was1·3 times that of those who had a negative urinalysisresult (95 % confidence interval 0·6–2·8).This relative risk remained the same after adjusting for ageand smoking. This indicates that there is a possibility thaturinary screening for microscopic haematuria could be a usefulpredictor of urological disease occurrence. However, the benefitsof early detection and management were difficult to demonstrate.Serious urological diseases, particularly urinary cancers, werenot detected earlier as a result of the urinary screening testin this study. Several studies have been done to validate thetest in the past. More work to validate the test and to determinethe predictive accuracy is recommended. Requests for reprints should be addressed to: Dr B. C. K. Choi, Occupational and Environmental Health Unit, Faculty of Medicine, University of Toronto, FitzGerald Building, 150 College Street, Toronto, Canada M5S 1A8     

Impact of mesangial IgA deposits in 14th-postoperative-day routine renal allograft biopsies

SUMMARY: Three hundred fourteen 14th-postoperative-day routine renal allograft biopsies were evaluated together with clinical data. Out of 314 biopsies, mesangial IgA deposits were positive in 122 biopsies (39%). According to Banff classification, the rate of acute rejection was significantly lower in mesangial IgA deposit-positive (IgA(+)) patients (7.4%) than in mesangial IgA deposit-negative (IgA(-)) patients (19.7%) on the 14th postoperative day. Thereafter, rate of biopsy-proven and clinical acute rejection was continuously lower for up to 12 months in IgA(+) patients than in IgA(-) patients. the detection rate of mesangial IgA deposits was significantly higher in human leucocyte antigen (HLA)-well-matched (HLA mismatch number was <3) patients than in HLA-poorly matched (HLA mismatch number was <3) patients. In HLA-well-matched patients, the serum creatinine levels were significantly lower in IgA(+) patients than in IgA(-) patients after 3 post-transplant months and up to 1 post-transplant year. Follow-up (mean interval: 13 months) allograft biopsies were performed in 34 patients out of 122 IgA(+) patients. In the follow-up biopsies, initially detected mesangial IgA deposits had disappeared in 22 patients (65%) out of 34 patients. Twelve patients (35%) still had mesangial IgA deposits, and all of them had clinical and pathological findings consistent with IgA nephropathy. Patients with continuous mesangial IgA deposits in the follow-up biopsies had a better renal function at 1 year and a higher 5-year graft survival rate compared with patients who lost the initially deposited IgA. the present study demonstrates that long-lasting mesangial IgA deposits in renal transplants prevent allografts from acute rejection, which leads to better graft outcome.     

MMP-2 regulates human platelet activation by interacting with integrin αIIbβ3

Summary. Background: Human platelets contain matrix metalloproteinases (MMPs) that are secreted during platelet activation. Platelet MMPs have been implicated in the regulation of cellular activation and aggregation. Although the proaggregatory effect of MMP‐2 has been demonstrated, the functional mechanism is not clearly understood. Objectives: This work was carried out in order to elucidate the biochemical mechanism of MMP‐2‐associated platelet activation and aggregation. Methods: MMP‐2 binding to the platelet surface was analyzed by flow cytometry. The cell surface target of MMP‐2 was identified in thrombin receptor‐activating peptide‐stimulated platelets by immunoprecipitation, Western blotting and fluorescence microscopy. A recombinant hemopexin‐like domain was used to characterize the nature of MMP‐2 binding to the platelet surface. The functional significance of MMP‐2 in platelet activation was investigated by quantitative measurements of the activation markers P‐selectin (CD62P) and active α_IIbβ₃. The role of MMP‐2 in platelet aggregation was analyzed with an aggregometer. Results: ProMMP‐2 binds to integrin α_IIbβ₃ in stimulated platelets in which proMMP‐2 is converted into MMP‐2. Fibrinogen was able to replace the α_IIbβ₃‐bound MMP‐2. The molecular interaction of MMP‐2 and integrin α_IIbβ₃ was abrogated by the recombinant human hemopexin‐like domain of MMP‐2, leading to reduced cell surface expression of activation markers CD62P and active α_IIbβ₃, and resulting in suppressed platelet aggregation. Conclusion: This work clearly demonstrates that platelet activation and aggregation is regulated by MMP‐2 that specifically interacts with integrin α_IIbβ₃. The C‐terminal hemopexin‐like domain of MMP‐2 is an essential element for binding to α_IIbβ₃.     

Long-term Results Following 131I Treatment for Graves' Disease in Hong Kong Chinese--Discriminant Factors Predicting Hypothyroidism

The clinical outcome of 1028 Hong Kong Chinese patients withGraves' disease treated with radioiodine therapy and followedfor a mean of 9.85±4.84 years (range 2–20) wasanalysed. Retreatment was required by 413 patients (40.2 percent), with 134 patients (13.0 per cent) requiring more thantwo ¹³¹I doses. One hundred and eighty-nine patients receivedcarbimazole after ¹³¹I until euthyroidism was achieved. Thecumulative incidence of hypothyroidism at one, five, 10 and15 years was 9.6 per cent, 31.4 per cent, 53.8 per cent and65.8 per cent, respectively. The average incidence of hypothyroidismafter the first two years was 3.3 per cent per annum. Stepwiselogistic regression analysis of pretreatment variables suggestedthat a combination of adjunctive carbimazole therapy, absenceof ophthalmopathy and longer effective half-lives of ¹³¹I wereof value in predicting which patients were less likely to developpermanent hypothyroidism. However, the probability of accuratelypredicting permanent hypothyroidism based on the present modelwas only 60 per cent. We believe that no single pretreatmentvariable, or combination of variables, predicts long-term hypothyroidismwith sufficient confidence to justify the use of a ‘formula’approach for prescribing ¹³¹I therapy for Graves' disease.     

Titanium Dioxide Exposure Induces Acute Eosinophilic Lung Inflammation in Rabbits

Titanium dioxide (TiO₂) is increasingly widely used in industrial, commercial and home products. TiO₂ aggravates respiratory symptoms by induction of pulmonary inflammation although the mechanisms have not been well investigated. We aimed to investigate lung inflammation in rabbits after intratracheal instillation of P25 TiO₂. One ml of 10, 50 and 250 µg of P25 TiO₂ was instilled into one of the lungs of rabbits, chest computed-tomography was performed, and bronchoalveolar lavage (BAL) fluid was collected before, at 1 and 24 h after P25 TiO₂ exposure. Changes in inflammatory cells in the BAL fluids were measured. Lung pathological assay was also carried out at 24 h after P25 TiO₂ exposure. Ground glass opacities were noted in both lungs 1 h after P25 TiO₂ and saline (control) instillation. Although the control lung showed complete resolution at 24 h, the lung exposed to P25 TiO₂ showed persistent ground glass opacities at 24 h. The eosinophil counts in BAL fluid were significantly increased after P25 TiO₂ exposure. P25 TiO₂ induced a dose dependent increase of eosinophils in BAL fluid but no significant differences in neutrophil and lymphocyte cell counts were detected. The present findings suggest that P25 TiO₂ induces lung inflammation in rabbits which is associated with eosinophilic inflammation.     

软组织硬度超声测试系统用于类风湿足底软组织评估

测量软组织的硬度能够评估某些疾病的严重程度,但是临床上广泛使用的触摸诊断只能根据操作者的感觉定性地给出一个硬度的变化值,结果很大程度上受制于操作者的经验,所以有必要开发定量客观评估软组织硬度的工具。本文介绍一种软组织硬度超声测试系统,该系统以超声探头作为印压头,以超声信号获取被测组织的形变,利用印压实验测量软组织的力学特性。在引言部分我们回顾了该系统到目前为止在各种软组织测试当中的应用,正文部分我们主要报导此系统用于测量类风湿病人足底软组织硬度的变化。测试结果显示,有足部畸形的类风湿病人的第五跖骨头下软组织硬度为（67.1±38.1）kPa,明显高于正常人（46.0±12.1）kPa（p=0.021）。类风湿病人第一和第五跖骨头下面软组织厚度也明显小于正常人（p=0.010及p=0.027）。实验结果证明类风湿病人的足部畸形会导致外侧跖骨头下软组织硬度的增加。该超声硬度测试系统还可以用来监测类风湿病人脚底软组织力学特性随病变时间的变化。     

CD40 ligand shedding is regulated by interaction between matrix metalloproteinase‐2 and platelet integrin αIIbβ3

Summary. Background: CD40 ligand (CD40L, CD154) in the circulatory system is mainly contained in platelets, and surface‐expressed CD40L on activated platelets is subsequently cleaved by proteolytic activity to generate soluble CD40L (sCD40L). However, the enzyme responsible for the shedding of CD40L in activated platelets has not been clearly identified yet. We have recently found that molecular interaction of matrix metalloproteinase‐2 (MMP‐2) with integrin α_IIbβ₃ is required for the enhancement of platelet activation. Objectives: To elucidate the biochemical mechanism of MMP‐2‐associated sCD40L release. Methods: Localization of MMP‐2 and CD40L in platelets was analyzed by flow cytometry and fluorescence microscopy. The release of sCD40L from activated platelets was measured by enzyme‐linked immunosorbent assay. MMP‐2 binding to α_IIbβ₃ was analyzed by immunoprecipitation and western blotting. Recombinant hemopexin‐like domain and MMP‐2‐specific inhibitor were used to characterize the nature of MMP‐2 binding and catalytic activity. Results: It was revealed that interaction of MMP‐2 with α_IIbβ₃ is required for effective production of sCD40L in activated human platelets. Platelet activation and release of sCD40L were significantly affected by inhibition of platelet‐derived MMP‐2 activity or by inhibition of binding between the enzyme and the integrin. It was also found in platelet‐rich plasma that MMP‐2 activity is responsible for generating sCD40L. Conclusions: The results presented here strongly suggest that MMP‐2 interacts with α_IIbβ₃ to regulate the shedding of CD40L exposed on the surfaces of activated human platelets.