Detection of Senile Plaque and Neurofibrillary Tangle using Bielschowsky-Hirano\u27s Silver Method

Conventional light microscopic morphometrical investigations were performed on senile plaques and neurofibrillary tangles in eighteen senile brains. Specimens from the hippocampal region were investigated statistically whether or not there is any difference in detection of senile plaques and neurofibrillary tangles among the conventional staining methods, that is, Hematoxylin-Eosin stain, Congo red stain, Periodic acid Schiff reaction, Bodian stain and Bielschowsky- Hirano\u27s silver stain. It was clarified that, even in the laboratory without specific antibody to senile plaque and neurofibrillary tangle, Bielschowsky-Hirano\u27s stain is the most useful and convenient staining method for detection of these ageing-related changes

Morphometrical Study on the Sclerotic Inferior Vena Cava in Chronic Lung Disease

The purpose of this study is to determine the relationship between chronic lung disease (CLD) and morphological changes in the inferior vena cava (IVC) from postmortem materials. The IVC and pulmonary truncus were obtained from 70 cases with CLD and/or cor pulmonale and from 23 controls. The tissues were processed for light and electron microscopic studies. The adventitia was by far the thickest component of the IVC wall. The total wall, intimal, and adventitial thicknesses were all significantly greater in the CLD cases than in the controls (p<0.001), but there was no significant difference in the ratio of adventitia thickness to wall thickness. The incidence of intimal thickening was 13.0% and 37.3% in controls and in CLD respectively. Electron microscopic examination of the IVC from the CLD cases revealeda marked increase in the amount of extracellular matrix including collagen, elastic fibers and ground substances in the adventitia as compared with the controls. No foam cells were detected in the thickened intima of the IVC. PA, right ventricular thickness and RV/LV ratio were greater in CLD than in controls. The blood gas levels of the CLD cases indicated obvious hypoxia (PaO2 54.2 mmHg). This study suggests that increased venous pressure and hypoxia might be implicated in the pathogenesis of phlebosclerosis in patients with CLD

Granular C3 Dermatosis

There has been no previous systematic study of bullous skin diseases with granular basement membrane zone deposition exclusively of C3. In this study we collected 20 such patients, none of whom showed cutaneous vasculitis histopathologically. Oral dapsone and topical steroids were effective. Various serological tests detected no autoantibodies or autoantigens. Direct immunofluorescence for various complement components revealed deposition only of C3 and C5?C9, indicating that no known complement pathways were involved. Studies of in situ hybridization and micro-dissection with quantitative RT-PCR revealed a slight reduction in expression of C3 in patient epidermis. These patients may represent a new disease entity, for which we propose the term “granular C3 dermatosis”. The mechanism for granular C3 deposition in these patients is unknown, but it is possible that the condition is caused by autoantibodies to skin or aberrant C3 expression in epidermal keratinocytes

Association of low ficolin-2 concentration in cord serum with respiratory distress syndrome in preterm newborns

IntroductionFicolin-2 is a serum pattern recognition molecule, involved in complement activation via the lectin pathway. This study aimed to investigate the association of ficolin-2 concentration in cord blood serum with complications related to premature birth.Methods546 premature neonates were included. The concentration of ficolin-2 in cord blood serum was determined by a sandwich TRIFMA method. FCN2 genetic variants were analysed with RFLP-PCR, allele-specific PCR, Sanger sequencing or allelic discrimination using TaqMan probes method.FindingsCord blood serum ficolin-2 concentration correlated positively with Apgar score and inversely with the length of hospitalisation and stay at Neonatal Intensive Care Unit (NICU). Multivariate logistic regression analysis indicated that low ficolin-2 increased the possibility of respiratory distress syndrome (RDS) diagnosis [OR=2.05, 95% CI (1.24-3.37), p=0.005]. Median ficolin-2 concentration was significantly lower in neonates with RDS than in premature babies without this complication, irrespective of FCN2 gene polymorphisms localised to promoter and 3’untranslated regions: for patients born &lt;33 GA: 1471 ng/ml vs. 2115 ng/ml (p=0.0003), and for patients born ≥33 GA 1610 ng/ml vs. 2081 ng/ml (p=0.012). Ficolin-2 level was also significantly lower in neonates requiring intubation in the delivery room (1461 ng/ml vs. 1938 ng/ml, p=0.023) and inversely correlated weakly with the duration of respiratory support (R=-0.154, p&lt;0.001). Interestingly, in the neonates born at GA &lt;33, ficolin-2 concentration permitted differentiation of those with/without RDS [AUC=0.712, 95% CI (0.612-0.817), p&lt;0.001] and effective separation of babies with mild RDS from those with moderate/severe form of the disease [AUC=0.807, 95% CI (0.644-0.97), p=0.0002].ConclusionLow cord serum ficolin-2 concentration (especially in neonates born at GA &lt;33 weeks) is associated with a higher risk of developing moderate/severe RDS, requiring respiratory support and intensive care

The dual role of complement in the progression of renal disease in NZB/W F1 mice and alternative pathway inhibition

► Complement plays a dual role in the pathogenesis of lupus. ► Selectively inhibiting the alternative complement pathway provides optimal protection from lupus nephritis. ► sCR2, the targeting moiety used to target deliver inhibitors to sites of complement activation, contributes to therapeutic outcome via modulation of autoimmunity. Complement plays a dual role in the progression of systemic lupus erythematosus since it has important protective functions, such as the clearance of immune complexes and apoptotic cells, but is also a mediator of renal inflammation. To investigate this balance in a clinically relevant setting, we investigated how targeted inhibition of all complement pathways vs. targeted inhibition of only the alternative pathway impacts immune and therapeutic outcomes in NZB/W F1 mice. Following onset of proteinuria, mice were injected twice weekly with CR2-fH (inhibits alternative pathway), CR2-Crry (inhibits all pathways at C3 activation step), sCR2 (C3d targeting vehicle) or saline. Sera were analyzed every 2 weeks for anti-dsDNA antibody levels, and urinary albumin excretion was determined. Kidneys were collected for histological evaluation at 32 weeks. Compared to the control group, all CR2-fH, CR2-Crry and sCR2 treated groups showed significantly reduced serum anti-dsDNA antibody levels and strong trends towards reduced glomerular IgG deposition levels. Glomerular C3 deposition levels were also significantly reduced in all three-treated groups. However, significant reductions of disease activity (albuminuria and glomerulonephritis) were only seen in the CR2-fH treated group. These data highlight the dual role played by complement in the pathogenesis of lupus, and demonstrate a benefit of selectively inhibiting the alternative complement pathway, presumably because of protective contributions from the classical and/or lectin pathways. The sCR2 targeting moiety appears to be contributing to therapeutic outcome via modulation of autoimmunity. Furthermore, these results are largely consistent with our previous data using the MRL/lpr lupus model, thus broadening the significance of these findings

The Effect of Ionizing Radiation on Epidermal Langerhans Cells:A Quantitative Analysis of Autopsy Cases with Radiation Therapy

Langerhans cells (LCs) are dendritic cells located in the epiderm is with antigen-presenting capacities. We performed a quantitative analysis of LC density in the anterior chest skin of 286 autopsy cases, including 31 cases treated with radiation therapy. Skin specimens were stained by immunoperoxidase technique (PAP method) with an anti-S-100 protein antiserum. S-100 positive LCs were counted for comparison between nonirradiated and irradiated cases. In this study we noted that, 1) The decline in density of the LCs was age-related and dendritic processes were more prominent in younger groups. 2) The cases irradiated within one month before autopsy showed a reduction in LC density compared with age-matched controls. 3) The cases irradiated more than one month before autopsy demonstrated no consistent or definite tendency. It is suggested that ionizing irradiation as well as ultraviolet light may deplete the LC density in an acute phase. The possibility that radiation therapy alters immunological surveillance in the human skin is discussed