Peroxisome proliferator-activated receptor ɣ agonist mediated inhibition of heparanase expression reduces proteinuria.

Background: Proteinuria is associated with many glomerular diseases and a risk factor for the progression to renal failure. We previously showed that heparanase (HPSE) is essential for the development of proteinuria, whereas peroxisome proliferator-activated receptor ɣ (PPARɣ) agonists can ameliorate proteinuria. Since a recent study showed that PPARɣ regulates HPSE expression in liver cancer cells, we hypothesized that PPARɣ agonists exert their reno-protective effect by inhibiting glomerular HPSE expression.

The Calcium-Dependent Protease Calpain-1 Links TRPC6 Activity to Podocyte Injury.

Background: The hallmark of podocytopathies, such as FSGS, is podocyte injury resulting in proteinuria. Transient receptor potential channel C6 (TRPC6) is a calcium-conducting ion channel expressed at the slit diaphragm. TRPC6 gain-of-function mutations and glomerular TRPC6 overexpression are associated with proteinuria.

IL-1β Promotes a New Function of DNase I as a Transcription Factor for the Fas Receptor Gene.

Recently we described that endonuclease inactive DNase I translocated into the nucleus in response to increased endogenous IL-1β expression. Here, we demonstrate impact and function of translocated DNase I in tubular cells. Effect of cytokines on expression level and nuclear localisation of DNase I and corresponding levels of Fas receptor (FasR) and IL-1β were determined by confocal microscopy, qPCR and western blot analyses, in presence or absence of siRNA against IL-1β and DNase I mRNA.

Sildenafil Prevents Podocyte Injury PPAR--Mediated TRPC6 Inhibition.

Transient receptor potential channel C6 (TRPC6) gain-of-function mutations and increased TRPC6 expression in podocytes induce glomerular injury and proteinuria. Sildenafil reduces TRPC6 expression and activity in nonrenal cell types, although the mechanism is unknown. Peroxisome proliferator-activated receptor (PPAR-) is a downstream target of sildenafil in the cyclic guanosine monophosphate (cGMP)-activated protein kinase G (PKG) axis.

1,25-Vitamin D3 Deficiency Induces Albuminuria.

Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1α-hydroxylase activity.

Vitamin D attenuates proteinuria by inhibition of heparanase expression in the podocyte.

The glomerular filtration barrier consists of podocytes, the glomerular basement membrane, and endothelial cells covered with a glycocalyx. Heparan sulphate (HS) in the glomerular filtration barrier is reduced in patients with proteinuria, which is associated with increased expression of the HS-degrading enzyme heparanase. Previously, we showed that heparanase is essential for the development of proteinuria in experimental diabetic nephropathy.

Glucose specifically regulates TRPC6 expression in the podocyte in an AngII-dependent manner.

Slit diaphragm and podocyte damage is crucial in the pathogenesis of proteinuria in diabetic nephropathy (DNP). Gain-of-function mutations in TRPC6, a slit diaphragm-associated ion channel, cause glomerulosclerosis; TRPC6 expression is increased in acquired glomerular disease. Hyperglycemia and high intrarenal angiotensin II (AngII) levels could contribute to podocyte injury in DNP.

Early development of hyperparathyroidism due to loss of PTH transcriptional repression in patients with HNF1β mutations?

Context: Heterozygous mutations or deletions of the transcription factor hepatocyte nuclear factor 1β (HNF1β) result in a heterogeneous syndrome characterized by renal cysts and diabetes, together with a variety of other extrarenal and renal manifestations. Interestingly, in several patients with HNF1β abnormalities, we observed early hyperparathyroidism and PTH levels that we judged inappropriately high compared with the degree of renal function decline.

Objective: Based on the above clinical observations, we tested the hypothesis of a direct role of HNF1β in the transcriptional regulation of the human PTH gene in the parathyroid gland.

Patients' priorities in assessing organisational aspects of a general dental practice.

Objectives: To explore which organisational aspects are considered most important by patients when assessing a general dental practice, and which patients' characteristics influence their views on these aspects by a paper questionnaire.

Participants: The questionnaire was handed out to a sample of 5,000 patients in the Netherlands.

Results: The response rate was 63%.

Vitamin D down-regulates TRPC6 expression in podocyte injury and proteinuric glomerular disease.

The transient receptor potential cation channel C6 (TRPC6) is a slit diaphragm protein expressed by podocytes. TRPC6 gain-of-function mutations cause autosomal dominant focal segmental glomerulosclerosis. In acquired proteinuric renal disease, glomerular TRPC6 expression is increased.

Organisational aspects of dental practices: do dental students think like patients or like general dental practitioners?

Introduction: In view of transparency in health care, the widespread desire for more patient-centred care, and in an attempt to facilitate educational programmes that effectively respond to these changes, two research questions are formulated: (i) How do dental students rate the importance of various organisational aspects of dental practices compared with dental patients and general dental practitioners (GDPs), and what prescripts, defined as specific operational responsibilities of GDPs in these matters, do dental students propose? and (ii) In doing so, do students resemble patients or GDPs?

Methods: In two survey studies, dental students (n = 198), patients (n = 3127) and GDPs (n = 303) were asked to rate by questionnaire the importance of 41 organisational aspects of a general dental practice and proposed specific operational responsibilities ('prescripts').

Results: Seven of 41 aspects were rated as important by the majority of the students. Although in a different rank order, three aspects were predominantly selected by all three groups: continuing education, accessibility by telephone and Dutch-speaking GDP.

Views of patients and general dental practitioners on the organizational aspects of a general dental practice.

Objective: To examine the views of patients and general dental practitioners (GDPs) on the organizational aspects of a general dental practice and to see whether their views differ.

Background: Health care has increasingly centred on the patient over the last two decades, and the patients' opinions have been taken more seriously. Although in other health-care sectors research on organizational aspects has been performed, research in dental care is lacking on this subject.

The estimation of patients' views on organizational aspects of a general dental practice by general dental practitioners: a survey study.

Background: Considering the changes in dental healthcare, such as the increasing assertiveness of patients, the introduction of new dental professionals, and regulated competition, it becomes more important that general dental practitioners (GDPs) take patients' views into account. The aim of the study was to compare patients' views on organizational aspects of general dental practices with those of GDPs and with GDPs' estimation of patients' views.

Methods: In a survey study, patients and GDPs provided their views on organizational aspects of a general dental practice.

[Quality of dental care: new ideas of the government].

In the 1990s the Dutch government imposed several laws to strengthen the position of the patient and to improve the quality of care. These laws did not always have the intended outcome. Recently the Ministry of Public Health, Welfare and Sport launched the programme, 'The 7 rights of the patient in health care: investing in health care relations'.

Haemopoietic growth factor tyrosine kinase receptor expression profiles in normal haemopoiesis.

Expression profiles were generated for the haemopoietic tyrosine kinase receptors (HGF-TKRs or class III TKRs) by PCR on cDNA samples (RT-PCR) using a degenerate primer set. Each profile consisted of primary and secondary, i.e.

Direct display of hematopoietic tyrosine kinase receptor expression profiles in KG1 cells by PCR using degenerate primers.

Hematopoietic tyrosine kinase receptors (HGF-TKRs or class III TKRs) are essential for the growth and differentiation of hematopoietic cells. In this report we present a novel method that generates expression profiles of these receptors. The method was tested and optimized using the myeloblastic/ promyelocytic cell line KG1.

Denaturing and non-denaturing gel electrophoresis as methods for the detection of junctional diversity in rearranged T cell receptor sequences.

Two nucleic acid gel electrophoresis techniques were tested as a possible tool for analyzing junctional diversity in rearranged T cell receptor (TcR) sequences in order to define the extent of T cell heterogeneity. For this purpose denaturing gradient gel electrophoresis (DGGE) as well as non-denaturing gel electrophoresis (nDGE) techniques have been studied. Detection of junctional diversity is based on mobility shifts, caused by nucleotide sequence polymorphism, of polymerase chain reaction amplified rearranged TcR sequences.