Adipose tissue at entheses: the innervation and cell composition of the retromalleolar fat pad associated with the rat Achilles tendon

This study set out to determine whether the fat pad at the attachment of the Achilles tendon has features enabling it to function as an immune organ and a mechanosensory device, and to be a source of pain in insertional tendon injuries. Sections for histology and immunohistochemistry were cut from the Achilles tendon enthesis organ of 1 day old, 1 month, 4 month and 24 month old rats. For fluorescence and peroxidase immunohistochemistry, cryosections were labelled with primary antibodies directed against PGP9.5, substance P, neurofilament 200, calcitonin gene related peptide, CD68, CD36, myeloid related protein 14, actin and vinculin. The fat pad contained not only adipocytes, but also fibrous tissue, mast cells, macrophages, fibroblasts and occasional fibrocartilage cells. It was richly innervated with nerve fibres, some of which were likely to be nociceptive, and others mechanoreceptive (myelinated fibres, immunoreactive for neurofilament 200). The fibres lay between individual fat cells and in association with blood vessels. In marked contrast, the enthesis itself and all other components of the enthesis organ were aneural at all ages. The presence of putative mechanoreceptive and nociceptive nerve endings between individual fat cells supports the hypothesis that the fat pad has a proprioceptive role monitoring changes in the insertional angle of the Achilles tendon and that it may be a source of pain in tendon injuries. The abundance of macrophages suggests that the adipose tissue could have a role in combating infection and/or removing debris from the retrocalcaneal bursa.     

Presynaptic D1 dopamine receptors facilitate glutamatergic neurotransmission in the rat globus pallidus

The effects of D1/5 dopamine agonists on spontaneous excitatory postsynaptic currents (sEPSCs) were studied in neurons of the rat globus pallidus using whole-cell recordings in the presence of TTX and bicuculline. In this condition, CNQX abolished the sEPSCs, indicating that they were solely mediated by AMPA receptors. SKF 38393, a D1-like agonist, increased the frequency but not the amplitude of the sEPSCs, suggesting a presynaptic site of action. The increase in frequency was blocked by SCH 23390, a D1/5 antagonist. Quinpirole, a D2-like agonist, decreased the frequency but did not affect the amplitude of the synaptic currents. SKF 38393 increased the frequency of sEPSCs currents, even in presence of quinpirole, indicating that D1/5- and D2-like receptors independently modulate glutamate release upon a single neuron. The results suggest that the dopaminergic control of the glutamate transmission in the globus pallidus may play a role in processing cortical information in the indirect pathway of the basal ganglia.     

Fructosamine-6-phosphates are deglycated by phosphorylation to fructosamine-3,6-bisphosphates catalyzed by fructosamine-3-kinase (FN3K) and/or fructosamine-3-kinase-related-protein (FN3KRP)

Nonenzymatic glycation of proteins and some phospholipids by glucose and other reducing sugars (a.k.a Maillard reaction) is an unavoidable result of the coexistence of these sugars and the affected macromolecules in living systems. The consequences of this process are deleterious both in the intracellular and extracellular environments as evidenced by the close association between increased nonenzymatic glycation and complications of diabetes. Because of these considerations, we have proposed that the intrinsic toxicity of glucose and other sugars is counteracted in vivo by active deglycation mechanisms including transglycation of Schiff's bases and FN3K-dependent breakdown of fructosamines. While this modified hypothesis is receiving increasing experimental support, several issues regarding glycation/deglycation remain unresolved. Two such important questions are In this paper we propose a resolution of both these quandaries by proposing that fructosamine-6-phosphates are deglycated by phosphorylation to fructosamine-3,6-bisphosphates catalyzed by FN3KRP and/or possibly FN3K. We provide some preliminary evidence in support of this hypothesis and outline experimental approaches for definitive tests of this hypothesis. The potential medical implications of this finding are not clear yet but, if correct, this observation is likely to have a major impact on our understanding of the very basic and hitherto unexplored aspect of glucose metabolism and chemistry in vivo. One can imagine that, at some point in the future, measurement of FN3K/FN3KRP activity may be of diagnostic value in assessing an individual's susceptibility to diabetic complications. Further down the road, one can also envision a gene therapeutic intervention to bolster FN3K/FN3KRP-based antiglycation defenses.     

"Stroop concordant" coloring of letters for remediation of dyslexia

In the modern society of the printed word dyslexia can be distressing and disabling. Commonly dyslexia manifests as a difficulty reading often caused by confusion or reversal of certain letters such as 'b' and 'd', and 'p' and 'q' and 'g'. Here we suggest that one method of remediation or amelioration is to print letters in color such as a 'b' in blue print, an 'r' in red, 'g' in green and 'p' in pink. Such coloring of letters takes advantage of the well-known association of vision of the color with the color's name--and therefore enunciation of the color's first letter.     

In vitro assembly of a prohead-like structure of the Rhodobacter capsulatus gene transfer agent

The gene transfer agent (GTA) is a phage-like particle capable of exchanging double-stranded DNA fragments between cells of the photosynthetic bacterium Rhodobacter capsulatus. Here we show that the major capsid protein of GTA, expressed in E. coli, can be assembled into prohead-like structures in the presence of calcium ions in vitro. Transmission electron microscopy (TEM) of uranyl acetate staining material and thin sections of glutaraldehyde-fixed material demonstrates that these associates have spherical structures with diameters in the range of 27-35 nm. The analysis of scanning TEM images revealed particles of mass approximately 4.3 MDa, representing 101+/-11 copies of the monomeric subunit. The establishment of this simple and rapid method to form prohead-like particles permits the GTA system to be used for genome manipulation within the photosynthetic bacterium, for specific targeted drug delivery, and for the construction of biologically based distributed autonomous sensors for environmental monitoring.     

Fluorescence in situ hybridization in diagnostic cytology

Fluorescence in situ hybridization (FISH) is a technique that uses fluorescently labeled DNA probes to detect chromosomal alterations in cells. FISH can detect various types of cytogenetic alterations including aneusomy (ie, abnormalities of chromosome copy number), duplication, amplification, deletion, and translocation. Because tumor cells generally contain chromosomal alterations, FISH is able to detect cells that have chromosomal abnormalities consistent with neoplasia in exfoliative and aspiration cytology specimens. This review will discuss the utility of FISH for the detection of bladder, lung, pancreatobiliary, and esophageal carcinoma in cytologic specimens.