Fetal and Perinatal Brain Autopsy: Useful Macroscopic Techniques Including Agar In-situ and Pre-Embedding Methods.

Fragile perinatal and fetal brains are the rule rather than the exception for developmental neuropathologists. Retrieving the fresh brain from the skull and examining early fetal, macerated or severely hydrocephalic brains after fixation can be a challenge. Textbooks on neurodevelopmental pathology mention these challenges to macroscopic examination of the developing central nervous system only in passing, but many perinatal pathologists recognize this diagnostic problem.

Distinct Differences on Neointima Formation in Immunodeficient and Humanized Mice after Carotid or Femoral Arterial Injury.

Percutaneous coronary intervention is widely adopted to treat patients with coronary artery disease. However, restenosis remains an unsolved clinical problem after vascular interventions. The role of the systemic and local immune response in the development of restenosis is not fully understood.

[Thrombus in a patent foramen ovale].

Background: A "thrombus in transit" is a relatively rare diagnosis involving a thrombus in a patent foramen ovale. Patent foramen ovale occurs in about 25% of the population. A thrombus in transit may lead to paradoxical arterial emboli in the cerebral circulatory system and the extremities, as well as other locations.

The Dutch Transplantation in Vasculitis (DUTRAVAS) Study: Outcome of Renal Transplantation in Antineutrophil Cytoplasmic Antibody-associated Glomerulonephritis.

Background: Data on the outcome of renal transplantation in antineutrophil cytoplasmic antibody-associated glomerulonephritis (AAGN) patients are still limited. In particular, how disease recurrence in the renal allograft defines graft outcome is largely unknown. Therefore, we conducted a multicenter observational clinical and histopathological study to establish recurrence rate of AAGN in the allograft and the impact of recurrence on allograft survival.

Incipient renal transplant dysfunction associates with tubular syndecan-1 expression and shedding.

Syndecan-1 is a transmembrane heparan sulfate proteoglycan involved in regenerative growth and cellular adhesion. We hypothesized that the induction of tubular syndecan-1 is a repair response to incipient renal damage in apparently stable, uncomplicated renal transplant recipients. We quantified tubular syndecan-1 in unselected renal protocol biopsies taken 1 yr after transplantation.

Genetic analysis of intracapillary glomerular lipoprotein deposits in aging mice.

Background: Renal aging is characterized by functional and structural changes like decreased glomerular filtration rate, and glomerular, tubular and interstitial damage. To gain insight in pathways involved in renal aging, we studied aged mouse strains and used genetic analysis to identify genes associated with aging phenotypes.

Methods: Upon morphological screening in kidneys from 20-month-old mice from 26 inbred strains we noted intracapillary PAS-positive deposits.

Circulating alpha-klotho levels are not disturbed in patients with type 2 diabetes with and without macrovascular disease in the absence of nephropathy.

Background: Diabetes is associated with a high incidence of macrovascular disease (MVD), including peripheral and coronary artery disease. Circulating soluble-Klotho (sKlotho) is produced in the kidney and is a putative anti-aging and vasculoprotective hormone. Reduced Klotho levels may therefore increase cardiovascular risk in diabetes.

Gaseous hydrogen sulfide protects against myocardial ischemia-reperfusion injury in mice partially independent from hypometabolism.

Background: Ischemia-reperfusion injury (IRI) is a major cause of cardiac damage following various pathological processes. Gaseous hydrogen sulfide (H2S) is protective during IRI by inducing a hypometabolic state in mice which is associated with anti-apoptotic, anti-inflammatory and antioxidant properties. We investigated whether gaseous H2S administration is protective in cardiac IRI and whether non-hypometabolic concentrations of H2S have similar protective properties.

Urinary CD8+ T-cell counts discriminate between active and inactive lupus nephritis.

Introduction: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Early detection of initial renal manifestations and relapses during follow-up is pivotal to prevent loss of renal function. Apart from renal biopsies, current urinary and serological diagnostic tests fail to accurately demonstrate the presence of active LN.

SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation.

Genome-wide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FEcreat) and bias of estimated glomerular filtration rate (eGFR).

The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney.

Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to determine the miRNA expression profiles of 10 ccRCC-derived cell lines and short-term cultures of PTEC and to correlate these with their gene expression and copy-number profiles. Using microarray-based methods, a significantly altered expression level in ccRCC cell lines was observed for 23 miRNAs and 1630 genes.

Novel insights in localization and expression levels of C5aR and C5L2 under native and post-transplant conditions in the kidney.

Aims: The complement system, and especially C5a, plays an important role in the pathophysiology of renal diseases and post-transplant renal injury. The two receptors for C5a are C5a receptor (C5aR) and C5a-like-receptor-2 (C5L2). Only renal C5aR expression has been reported, although exact localization and alterations in expression after transplantation are unknown.

UMOD as a susceptibility gene for end-stage renal disease.

Background: In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant.

Methods: To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls.

Urine levels of HMGB1 in Systemic Lupus Erythematosus patients with and without renal manifestations.

Introduction: Lupus nephritis (LN) is a severe and frequent manifestation of systemic lupus erythematosus (SLE). Its pathogenesis has not been fully elucidated but immune complexes are considered to contribute to the inflammatory pathology in LN. High Mobility Group Box 1 (HMGB1) is a nuclear non-histone protein which is secreted from different types of cells during activation and/or cell death and may act as a pro-inflammatory mediator, alone or as part of DNA-containing immune complexes in SLE.

Beneficial effects of gaseous hydrogen sulfide in hepatic ischemia/reperfusion injury.

Hydrogen sulfide (H2 S) can induce a reversible hypometabolic state, which could protect against hypoxia. In this study we investigated whether H2 S could protect livers from ischemia/reperfusion injury (IRI). Male C57BL/6 mice were subjected to partial hepatic IRI for 60 min.

CUBN as a novel locus for end-stage renal disease: insights from renal transplantation.

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study).

Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation.

Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft protocol biopsies, renal allograft biopsies taken at indication, and non-transplant interstitial fibrosis. Syndecan-1 expression was increased in tubular epithelial cells in renal allograft biopsies compared with control.

Lectin complement pathway gene profile of the donor and recipient does not influence graft outcome after kidney transplantation.

In kidney transplantation, complement activation was found to be induced by donor brain death, renal ischemia-reperfusion injury and allograft rejection. There are three known pathways of complement activation: the classical, lectin and the alternative pathway. The lectin complement pathway can be activated upon pattern recognition by mannan binding lectin (MBL) or ficolins (FCN).

[From 'malignancy' to IgG4-related systemic disease].

IgG4-related systemic disease is a new clinical entity with a large variety of clinical symptoms that can affect almost all organs. The best known manifestations are retroperitoneal fibrosis and autoimmune pancreatitis. We present 3 patients aged 71, 83 and 70 years, with malaise, fatigue and swellings suggestive of a malignancy.

ADAM17 up-regulation in renal transplant dysfunction and non-transplant-related renal fibrosis.

Background: Interstitial fibrosis and tubular atrophy (IF/TA) is an important cause of renal function loss and ischaemia-reperfusion (I/R) injury is considered to play an important role in its pathophysiology. The aim of the present study was to investigate the role of a disintegrin and metalloproteinase 17 (ADAM17) in human renal allograft disease and in experimental I/R injury of the kidney.

Methods: We studied the expression of ADAM17 messenger RNA (mRNA) in IF/TA and control kidneys by reverse transcription-polymerase chain reaction and in situ hybridization.

Uromodulin in renal transplant recipients: elevated urinary levels and bimodal association with graft failure.

Background: Urinary uromodulin (UMOD) predicts renal prognosis in native kidneys, but data are conflicting. We investigated its prognostic impact for graft failure (GF) in renal transplant recipients (RTR; n = 600).

Methods: UMOD concentration was measured cross-sectionally in RTR at 6.

HRAS-mutated Spitz tumors: A subtype of Spitz tumors with distinct features.

It is often very difficult to confidently distinguish benign and malignant Spitz lesions, and a diagnosis of Spitz tumor of unknown malignant potential (STUMP) is rendered. To address this problem, we performed molecular genetic analysis in a large group of Spitz tumors (93 Spitz nevi and 77 STUMPs) and identified a subgroup of 24 lesions harboring a HRAS mutation. This subgroup lay predominantly in the dermis, had a relatively low cellularity, showed desmoplasia (with single cells interspersed between the collagen bundles), and had an infiltrating base.

Urinary T cells in active lupus nephritis show an effector memory phenotype.

Background: Systemic lupus erythematosus (SLE) is accompanied by alterations in T cell homeostasis including an increased effector response. Migrated effector memory T cells (CD45RO(+)CCR7⁻; T(EM)) appear to be involved in tissue injury. The objective of this study was to investigate the distribution and phenotype of effector memory T cells in the peripheral blood (PB), and their presence in renal biopsies and urine of patients with SLE.