The serine racemase mRNA is predominantly expressed in rat brain neurons

D-serine is an endogenous and obligatory coagonist for the glycine site of the N-methyl-D-aspartate receptor in the mammalian brain. D-serine is synthesized from L-serine by serine racemase; immunohistochemical studies have long been believed to indicate that serine racemase and D-serine occur predominantly in astrocytes. However, we have recently demonstrated in the primary cultures that both the mRNA and protein levels of serine racemase are higher in neurons than in astrocytes. Here we report the application of in situ hybridization based on tyramide signal amplification for the detection of serine racemase mRNA in sections of the adult rat brain. Serine racemase mRNA could be demonstrated in a large number of neurons throughout the brain, especially in the forebrain such as the cerebral cortex, striatum, and hippocampus. This is the first study to demonstrate the exact localization of serine racemase mRNA at the cellular or tissue level. These results suggest that neuron-derived D-serine could modulate neurotransmission via the glycine site of N-methyl-D-aspartate receptors.     

Trigeminal schwannomas: experience with 57 cases and a review of the literature

Neurosurgical Review - Trigeminal schwannoma is a mostly benign tumor that can be cured by complete resection. Over the last few decades, several pioneers have developed surgical approaches...     

Molecular approaches to the study of renal disease

Summary: Recent developments in cell biology and molecular biology have provided new techniques for molecular studies on renal diseases. the in situ hybridization technique demonstrates the site and the degree of gene expression of various cytokines and regulating proteins associated with the altered function of the glomeruli. It is not known, however, if the expression of these genes is different among various glomerular diseases. the aim of this study was to elucidate the disease specific phenomena in glomerular gene expression. Renal biopsy specimens were obtained from patients with diabetic nephropathy, and IgA nephropathy. the degree of tissue damage as well as the levels of various clinical parameters were matched between these two groups. In situ hybridization of mRNA in renal tissues for transforming growth factor (TGF)-β, storomelysin (MMP-3) and tissue inhibitor of metalloproteinase (TIMP-1) were performed using nonradioactive digoxigenin (DIG)-labelled oligonucleotide probes. In parallel studies, renal biopsy specimens were stained with monoclonal antibody against advanced glycated end-products (AGE). the results demonstrated that the distribution of mRNA expression of TGF-β was similar between these two diseases, but the expression of MMP-3 and TIMP-1 was parallel with the degree of tissue damage in patients with IgA nephropathy while it was diminished in patients with an advanced degree of tissue damage due to diabetic nephropathy. Positive staining of renal tissues with anti-AGE antibody was only observed in patients with diabetic nephropathy. It is concluded that glycation of renal structural proteins might interfere with their metabolism by enzymes and their inhibitors, while a cytokine responsible for mesangial expansion was similarly expressed.     

Immunohistochemical staining of renal biopsy samples in patients with diabetic nephropathy in non-insulin dependent diabetes mellitus using monoclonal antibody to advanced glycation end products

Summary: Immunohistochemical staining of glomeruli in patients with diabetic nephropathy (DN) in non-insulin dependent diabetes mellitus (NIDDM) using the monoclonal anti-advanced glycation end products (AGE) antibody is described. In order to detect the localization of AGE in human renal tissues, we performed immunohistochemical staining using the monoclonal anti-AGE antibody in the glomeruli of 11 patients with DN and 11 age-matched patients with diffuse mesangial proliferative glomerulonephritis without IgA deposition (DPGN) as controls.
Emergence of AGE in the mesangial area was more marked in the glomeruli of patients with severe mesangial expansion than in those with mild expansion. AGE in the extraglomerular arteriolar walls was also observed. In contrast, there was no positive staining using the same antibody in renal tissue obtained from DPGN.
These data support the concept that deposition and/or formation of AGE in the mesangial area might be associated with the progression of diabetic nephropathy.