Immunological investigations in inbred mice chronically infected with cytopathogenic agents isolated from human cases of Balkan endemic nephropathy

An experimental chronic infection was induced in inbred A2G and CBA mice by repeated administration of four cytopathogenic agents isolated from human cases of Balkan endemic nephropathy (BEN). The slight humoral and cell-mediated immune responses to the BEN agents recorded in A2G mice were associated with autoimmunity and hypersensitivity phenomena. In contrast, the normal, intense immune response observed in CBA mice was not accompanied by any immunopathological changes. In both mouse lines the chronic infection with human BEN agents led to a secondary immune deficiency against sheep red blood cells or tuberculin.     

Investigations on the presence of antibodies to papova viruses in patients with different forms of cancer and in other categories of patients or apparently healthy subjects. Note I. Neutralizing antibodies to SV-40 in the cerebrospinal fluid of patients with brain tumors and chronic neurological diseases

Neutralizing antibodies to SV-40 were detected in cerebrospinal fluid samples from 16 out of 43 patients with brain tumors and in 6 out of 20 patients with different nonmalignant chronic neurological diseases. The patients' age excluded the correlation with a vaccine-associated or occupational contact with SV-40. The results ascertain the occurrence of SV-40 or of an antigenically related virus in the population of Romania.     

Possible relation between viruses and oromaxillofacial tumors. III. Demonstration of the SV40 antigen and anti-SV40 antibodies in patients with tumors of the parotid gland

SV40 antigen was detected in 7 of 13 malignant tumors developed in the head and neck region. Specific complement fixing antibodies were found in all the patients with the SV40 antigen present in the parotid gland tumoral cells. Incidence of the anti-SV40 complement fixing antibodies in parotid gland tumor bearing patients was of 69.6%.     

Ochratoxin A in human sera in the area with endemic nephropathy in Croatia

Ochratoxin A (OA) is nephrotoxic fungal metabolite (mycotoxin) occurring in foodstuffs. The compound is causally associated with mycotoxin porcine nephropathy, a disease comparable with a human kidney disease called endemic nephropathy (EN). In this paper we presented results obtained over a 10-year period in the hyperendemic village Kaniža, and in control villages where no clinical cases of nephropathy had been found. In the hyperendemic village Kaniža and non-endemic villages the incidence of OA in human blood was up to 4.5% (range 2–50 ng/ml) and up to 2.4% (range 2–10 ng/ml), respectively. Almost all samples of food and feed, collected randomly in the hyperendemic village were found to contain OA. Considering marked exposure to OA in Kaniža, it was assumed that incidence of EN in this population could be related to OA contamination of food and feed. Ireland Ltd.     

The role of lecithin cholesterol acyltransferase and organic substances from coal in the etiology of Balkan endemic nephropathy: a new hypothesis.

Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p=0.02) and (p=0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population.     

Possible relation between viruses and oromaxillofacial tumors. II. Research on the presence of the SV40 antigen and specific antibodies in patients with oromaxillofacial tumors

SV40 antigen was detected on sections through malignant oromaxillofacial tumors in 47.8% of the cases, with a higher incidence among the epithelium originating tumors. Anti-SV40 CF antibodies were detected in 83.6% of the examined subjects with cancer, but only in 57.9% of the blood donors. The titers were quite low in general. The results are discussed from the point of view of the immunologic status of the patients.     

Relevance of a rat model of papillary necrosis and upper urothelial carcinoma in understanding the role of ochratoxin A in Balkan endemic nephropathy and its associated carcinoma.

Ochratoxin A is nephrotoxic and has been implicated in the genesis of Balkan endemic nephropathy (BEN), a condition that leads to end-stage renal disease and upper urothelial tumours. This compound induces renal parenchymal carcinoma in male mice only, and is not considered to be a potent carcinogen nor is there experimental evidence of its propensity to cause upper urothelial carcinoma. There is, however, evidence that exposure to more than one mycotoxin may be an important factor in the clinical spectrum of BEN. Analgesic nephropathy is clinically different, but is also associated with an upper urothelial carcinoma. The combination of urothelial initiation and an acute papillary necrosis in rats produces upper urothelial carcinoma. This two-stage experimental model offers the potential to assess the role of ochratoxin A in BEN-associated upper urothelial carcinoma under experimental conditions.     

燃煤型地方性氟中毒病区人血浆H_2S、Hcy、VitB_6、VitB_(12)和叶酸水平的变化

目的观察燃煤型地方性氟病区人血浆硫化氢(H2S)及其代谢相关氨基酸的水平。方法采用离子选择电极、亚甲基蓝法和酶联免疫吸附法检测氟病区人血浆氟、H2S、同型半胱氨酸(Hcy)、VitB6、VitB12和叶酸(FA)的水平。结果与对照组相比,氟病区患者均有明显的氟斑牙,血浆氟含量明显增加(P<0.01),而H2S含量则明显降低(P<0.05);血浆Hcy、VitB6、VitB12和FA的水平在两组差异均无显著性(P>0.05)。结论燃煤型地方性氟中毒可明显降低人血浆H2S的水平,这可能与地氟病区人神经系统损伤有关。     

Comparative h NMR metabolomic urinalysis of people diagnosed with balkan endemic nephropathy, and healthy subjects, in romania and bulgaria: a pilot study

(1)H NMR spectroscopy of urine has been applied to exploring metabolomic differences between people diagnosed with Balkan endemic nephropathy (BEN), and treated by haemodialysis, and those without overt renal disease in Romania and Bulgaria. Convenience sampling was made from patients receiving haemodialysis in hospital and healthy controls in their village. Principal component analysis clustered healthy controls from both countries together. Bulgarian BEN patients clustered separately from controls, though in the same space. However, Romanian BEN patients not only also clustered away from controls but also clustered separately from the BEN patients in Bulgaria. Notably, the urinary metabolomic data of two people sampled as Romanian controls clustered within the Romanian BEN group. One of these had been suspected of incipient symptoms of BEN at the time of selection as a 'healthy' control. This implies, at first sight, that metabolomic analysis can be predictive of impending morbidity before conventional criteria can diagnose BEN. Separate clustering of BEN patients from Romania and Bulgaria could indicate difference in aetiology of this particular silent renal atrophy in different geographic foci across the Balkans.     

Pharmacokinetics of sirolimus (rapamycin) in subjects with mild to moderate hepatic impairment

Eighteen adult subjects with mild to moderate hepatic impairment and 18 healthy control subjects were given a single 15-mg dose of sirolimus by oral solution. Mean whole-blood sirolimus weight-normalized oral-dose clearances (CL/F) were significantly decreased (P = .02) in subjects with mild to moderate hepatic impairment by -31.8% and -36.0%, respectively, compared with controls. There were no significant differences in mean sirolimus C(max) and t(max) values among groups. The observed decreases in CL/F may be relevant in renal transplant patients with mild to moderate hepatic impairment, based on the close similarity of sirolimus CL/F in controls and previously studied stable renal transplant patients receiving multiple-dose administration of sirolimus and cyclosporine. There was considerable overlap in the CL/F values of hepatic-impaired subjects and controls, suggesting that whole-blood sirolimus trough concentrations in renal transplant patients exhibiting mild to moderate hepatic impairment be initially monitored to assess the need for dose adjustments.     

Serum antibodies to collagen type IV and development of diabetic vascular complications in children with type 1 (insulin-dependent) diabetes mellitus. A longitudinal study

Thickening of basement membrane in capillaries and small vessels is a well-known finding and important in the progression of diabetic microangiopathy. To monitor the metabolism of the basement membrane protein collagen type IV (CIV) in diabetes mellitus, serum levels of IgG, IgM and IgA to CIV were measured using an ELISA method in 28 children with Type 1 diabetes mellitus over a period of 6 years. These values were compared to serum antibodies to CIV in 24 age- and sex-matched controls. At the end of the study, 11 children had diabetic microangiopathy. IgG to CIV was associated with age (r = .33, P = .026), diabetes duration (r = .32, P = .021), HbA1c (r = .31, P = .019), microalbuminuria (r = .32, P = .022) and anti-AGE antibodies (r = .47, P = .0007). IgM to CIV correlated with age (r = .46, P = .001), diabetes duration (r = .45, P = .001), HbA1c (r = .26, P = .038) and anti-AGE antibodies (r = .26, P = .038) and IgA to CIV with triglycerides (r = .29, P = .038) and anti-AGE antibodies (r = .44, P = .0025). We suggest that serum levels of IgG to CIV can be used as a marker for the development of diabetic microalbuminuria.     

Double immunofluorescence studies of IgA and poly C9 (MAC) in glomeruli from patients with IgA nephropathy

Double immunofluorescent studies on IgA, poly (MAC) or C3 in glomeruli from patients with IgA nephropathy are described. Renal biopsy specimens were obtained from 12 patients with IgA nephropathy, four patients with proliferative glomerulonephritis (PGN) and two normal human kidney (NHK). These specimens were incubated with monoclonal anti-poly C9 (membrane attack complex; MAC) and then stained with FITC-labelled goat anti-mouse immunoglobulin (Ig) antiserum. After washing with phosphate buffered saline (PBS) (pH 7.4), the sections were stained with rhodamine-labelled rabbit anti-human IgA antiserum and examined by fluorescence microscopy. The sections were also stained with FITC-labelled goat anti-human C3 antiserum and then stained with rhodamine-labelled rabbit anti-human IgA antiserum. Markedly combined depositions of IgA and poly C9 or C3 in glomeruli were observed in patients with IgA nephropathy. There was a significant correlation between the deposition of poly C9 and the grading of histopathological injuries in such patients. There was also a significant correlation between the deposition of poly C9 in the extraglomerular vascular vessels and the ageing in patients with IgA nephropathy, PGN and NHK. It appears that the deposition of poly C9 might detect directly the activities of complement in glomeruli from patients with IgA nephropathy.     

Antagonizing bradykinin (BK) obliterates the cardioprotective effects of bradykinin and angiotensin-converting enzyme (ACE) Inhibitors in ischemic hearts

Bradykinin (BK) (1 × 10 ^?12?1 × 10^?8 mol/l) and the ACE inhibitor ramiprilat (2.58 × 10 ^?9?2.58 × 10^?5 mol/l) markedly reduced the incidence and duration of reperfusion arrhythmias in the isolated ischemic rat heart. Pretreatment with ramipril (1 mg/kg p.o.), enalapril (10 mg/kg p.o.), but not captopril (50 mg/kg p.o.) had similar effects. Active compounds also improved cardiodynamics and reduced lactate dehydrogenase (LDH) and creatine kinase (CK) activities, as lactate formation in coronary venous effluent. Cardiac tissue levels of glycogen, adenosine triphosphate (ATP), and creatine phosphate (CP) were preserved. The BK antagonist D-Arg-[Hyp², Thi^5,8, D-Phe⁷]BK abolished the beneficial effects of BK, ramipril, and ramiprilat in a competitive way. Increased concentrations of BK or ramiprilat were able to reverse the antagonism. In anesthetized dogs an infusion of BK, at the dose of 1 ng/kg/min during coronary occlusion and reperfusion was devoid of cardiovascular effects but reduced mortality and the decrease of LDH activity and lactate concentration in coronary sinus blood and preserved tissue levels of glycogen and energy-rich phosphates in the ischemic myocardium.     

Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis

SUMMARY: Antibody titers to P. gingivalis are increased in patients with rheumatoid arthritis and are associated with disease-specific autoimmunity. BACKGROUND: Periodontitis (PD) has been implicated as a risk factor for rheumatoid arthritis (RA). We sought to characterize antibody titers to P. gingivalis (a pathogen in PD) in subjects with RA, PD, and in healthy controls and to examine their relationship with disease autoantibodies. METHODS: P. gingivalis antibody was measured in subjects with RA (n=78), PD (n=39), and in controls (n=40). Group frequencies of bacterial titer elevations were compared using the Chi-square test and antibody titers were compared using non-parametric tests. Correlations of P. gingivalis titer with C-reactive protein (CRP), antibody to cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were examined in those with RA while CRP and autoantibody concentrations were compared based on seropositivity to P. gingivalis. RESULTS: Antibody titers to P. gingivalis were highest in PD, lowest in controls, and intermediate in RA (p=0.0003). Elevations in P. gingivalis (titer> or =800) were more common in RA and PD (67% and 77%, respectively) than in controls (40%) (p=0.002). In RA, there were significant correlations with P. gingivalis titer with CRP, anti-CCP-IgM, and -IgG-2. CRP (p=0.006), anti-CCP-IgM (p=0.01) and -IgG2 (p=0.04) concentrations were higher in RA cases with P. gingivalis titers > or =800 compared to cases with titers <800. CONCLUSION: Antibodies to P. gingivalis are more common in RA subjects than controls, although lower than that in PD. Associations of P. gingivalis titers with RA-related autoantibody and CRP concentrations suggests that infection with this organism plays a role in disease risk and progression in RA.     

Presence of antibodies to human cytomegalovirus in patients with different forms of cancer and in other categories of subjects

Complement fixing (CF) antibodies to the AD--129 strain of human cytomegalovirus (HCMV) were detected in patients with different forms of cancer, as well as in blood donors, in a proportion of 16.6% and 73.2%, respectively. The prevalence of CF antibodies to HCMV, strain AT--129, in the population of Romania is similar to that reported in other countries.     

心肌梗塞患者血清脂蛋白（a）水平和纤溶功能

采用临床病例对照研究，分析56例心肌梗塞（MI）患者血清脂蛋白（a）（LP（a））水平和纤港功能。结果显示；MI组Lp（a）水平明显高于对照组（227mg／L与136mg／L，P＜0．001），多因素分析控制年龄、体重指数、腰臀比、血压、烟酒史、血脂质、纤维蛋白原、血糖和胰岛素后，MI组Lp（a）仍呈非常显著意义（P＝0．0037。MI组纤溶酶原活化物的抑制物（PAI－1）为11．23AU／ml，高于对照组（9.57AU／ml，P＜0.05），同样用多因素分析控制上述因素后，MI组PAI-1仍有显著意义。Lp（a）与PAI－1之间无明显相关性。多元逐步回归分析发现胰岛素与Lp（a）有关，体重指数和年龄与PAI－1有关。