New insights on P2X purinoceptors

Significant advances in understanding of P_2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown. Despite these issues, convincing evidence for P_2X receptor heterogeneity, from data with agonists, has recently been reported.A number of new antagonists at P_2X purinoceptors have also recently been described which to some degree appear to be more specific and useful than earlier antagonists like suramin. It is now apparent that suramin is a poor antagonist of ATP in many tissues because it potently inhibits ATPase activity at similar concentrations to those at which it blocks the P_2X purinoceptor.Advances in the use of radiolabelled nucleotides as radioligands for binding studies has allowed the demonstration of P_2X purinoceptors in a variety of tissues throughout the body including the brain. These studies have also provided evidence for receptor heterogeneity. Excitingly, two P_2X purinoceptor genes have been cloned but operational studies suggest that more than two types exist. The cloning studies have also demonstrated a unique structure for the P_2X purinoceptor which differentiates it from all other ligand-gated ion channel receptors. Further studies on P_2X purinoceptor operation and structure are needed to help resolve controversies alluded to regarding the characterization and classification of nucleotide receptors. Hopefully such studies will also lead to a better understanding of the physiological and pathological importance of ATP and its activation of P_2X purinoceptors. This will require the identification of better drug tools, in particular antagonists which may also provide the basis for novel therapeutic agents.     

MHC class II (I-A) region control of the IgE antibody repertoire to the ABA-1 allergen of the nematode Ascaris

ABA-1 is an approximately 14,000 molecular weight (MW) allergen which is among the most abundant proteins synthesized by the nematode parasite Ascaris. IgG and IgE responses to it are major histocompatibility complex (MHC)-restricted in rodents and have only been found to occur in rats of the RT1u haplotype and mice of the H-2s haplotype. Humans infected with the parasite vary substantially in their immune response to the allergen, but the genetic basis for this unknown. H-2 recombinant mice were used to identify the region within the MHC controlling antibody responses to the allergen. IgG antibody to immunoaffinity purified ABA-1 was assayed by radio-immunoassay and IgE by passive cutaneous anaphylaxis. This showed that the restriction element is the I-A molecule and that there was some evidence for I-E modulation of the level of response.     

A model for the prediction of osmolalities of modular formulas

A model is proposed for evaluation of osmolality of multicomponent formulas composed of modular ingredients. Nonlinear curve-fitting techniques applied to empirical data result in prediction of the osmolality of ingredients for any concentration desired. Osmolality of a multicomponent formula can be obtained by adding osmolalities of ingredients. Data handling is made possible by the use of simple microcomputer programs. The model is tested with products available for construction of amino acid-restricted diets.     

Calcium phosphate in catheter encrustation

Encrusted catheters from nine female patients were the source of samples of deposits which were examined by X-ray diffraction, atomic absorption spectroscopy, infra-red spectroscopy and extended X-ray absorption fine structure (EXAFS) spectroscopy. In eight samples the only crystalline phase which could be clearly distinguished by X-ray diffraction was ammonium magnesium orthophosphate hexahydrate, NH4MgPO4 X 6H2O, which occurs naturally as the mineral struvite. However, atomic absorption spectroscopy revealed an appreciable concentration of calcium in all samples. Calcium phosphates have previously been detected in catheter deposits. Infra-red and EXAFS spectra were consistent with the calcium phosphate being present as a poorly crystalline hydroxyapatite. Thus the deposits appear to consist of a mixture of crystalline struvite and a form of hydroxyapatite which is not fully crystalline.     

A review of intra-articular knee injuries in racquet sports diagnosed by arthroscopy

Because of the recent rapid increase in the number of knee injuries related to racquet sports, the authors undertook a retrospective study of such injuries seen over a 5-year period at the Toronto Western Hospital Sports Medicine Institute. The 121 patients who presented over the study period with a racquet-sports-related knee injury requiring arthroscopy represented 30% of all racquet-sports related injuries seen during that period. The mean age at presentation was 32.8 years and two-thirds of the patients were men. All the major racquet sports were represented. In all, 213 lesions (7 bilateral) were seen at 128 arthroscopies, and 165 arthroscopic procedures were performed. The most common lesion was meniscal followed by chondromalacia patellae, anterior cruciate ligament tears, chondral lesions and pathologic plicae. Over 90% of the patients returned to their chosen racquet sport within 3 months of the arthroscopy and most were playing at a similar performance level to that before the initial injury.     

Repression of the embryonic myosin heavy chain phenotype in regenerating chicken slow muscle is dependent on innervation.

Ventricular-like and fast myosin heavy chains (VL-MHC and FMHC) are transiently expressed during slow skeletal muscle development. The influence of innervation on repression of these MHC isoforms is investigated over an 84-day time course in: (1) normal anterior latissimus dorsi (N-ALD) muscles, (2) regenerating ALD (R-ALD) muscles, (3) denervated ALD (D-ALD) muscles, and (4) regenerating and denervated ALD (RD-ALD) muscles. Western blotting demonstrates that the VL-MHC is expressed in R-, D-, and RD-ALD muscles, but not in N-ALD muscles. Expression of the VL-MHC is transient in R-ALD muscles. In contrast, VL-MHC expression persists in RD-ALD muscles, and appears with time in D-ALD muscles. FMHC was not detected in N-ALD muscles by Western blotting. Two FMHCs are seen in R-ALD and RD-ALD muscles, and in 13-day embryonic ALD muscles. The slower migrating FMHC (FMHCA) comigrates with developmentally regulated FMHCs in fast pectoralis muscle, while the faster migrating FMHC (FMHCB) comigrates with the faster migrating FMHC in embryonic ALD muscle (13 days in ovo). FMHCB decreases in amount over the time course in R-ALD muscles, while FMHCA persists. In contrast, substantial levels of both FMHCs persist in RD-ALD muscles, and appear with time in D-ALD muscles. The cellular distribution of MHCs is followed by immunocytochemistry. Regenerating cells expressing VL-MHC and FMHC are replaced by a mature population in R-ALD muscles. Some of the mature myofibers in R-ALD muscles express FMHC, but not VL-MHC. In RD-ALD and D-ALD muscles, both regenerating and mature muscle cells are seen which express VL-MHC and FMHC. Our results indicate that innervation is required for the repression of VL-MHC and FMHCB during regeneration of slow muscle.