Vascular delay of the latissimus dorsi muscle: an essential component of cardiomyoplasty

BACKGROUND: Cardiomyoplasty (CMP) uses the latissimus dorsi muscle (LDM) to assist the heart in cases of cardiac failure. Distal ischemia and necrosis of the LDM is a recognized complication of CMP that can reduce distal muscle function and the mechanical effectiveness of CMP. METHODS: Canine (n = 9) LDMs were subjected to a 10-day period of vascular delay followed by a simulated CMP. Two weeks after simulated CMP (corresponding to the healing delay between CMP and the onset of LDM stimulation used in the clinical setting), LDM perfusion was measured in the distal, middle, and proximal segments of the muscle, and circumferential (distal and middle squeezing muscle function) and longitudinal (proximal pulling muscle function) force generation and fatigue rates were measured. The results were compared with the contralateral nondelayed simulated CMP. RESULTS: Muscle perfusion was significantly (p < 0.05) greater in the distal and middle segments of vascular-delayed LDMs. Circumferential muscle force generation and fatigue rates were significantly (p < 0.05) improved in the vascular-delayed LDMs. CONCLUSIONS: Vascular delay can significantly improve LDM perfusion and function in a model that closely reflects clinical CMP, and the use of vascular delay may improve clinical outcomes in CMP.     

Relationship of endometrial thickness with the menstrual timing of leuprolide acetate administration for preoperative preparation for hysteroscopic surgery

OBJECTIVES: To investigate the changes in the cholesterol:phospholipids (C/PL) ratio of erythrocyte membrane in post-menopausal women with and without hormone replacement therapy (HRT). STUDY DESIGN: A cross-sectional study including 83 patients divided into three groups according to HRT (group 1, no HRT (n = 52); group 2, combined HRT (n = 16); and group 3, estrogen-only therapy (n = 15)). RESULTS: The C/PL ratio was lower in group 2 with respect to group 1 and group 3 (P = 0.03). No difference was found in erythrocyte membrane cholesterol between the three groups; however, the phospholipid concentration was higher in group 2 with respect to the other groups (P < 0.05). In the control group, C/PL values correlated positively with plasma LDL levels (P < 0.005) and negatively with HDL levels (P < 0.005). CONCLUSIONS: From our data the addition of progestogens in HRT appears to decrease the C/PL of the erythrocyte membrane possibly resulting in a beneficial effect on rheological properties of erythrocyte membrane. The results of our study thus suggest additional benefits from supplementation of progestogens in HRT, in addition to prevention of estrogen dependent endometrial hyperplasia and adenocarcinoma.     

Pulmonary lesions in experimental ophidian paramyxovirus pneumonia of Aruba Island rattlesnakes, Crotalus unicolor

Histologic and ultrastructural changes were observed in the respiratory portions of lung in five 29-40-month-old Aruba Island rattlesnakes, Crotalus unicolor, that were inoculated with an Aruba Island Rattlesnake virus (AIV) strain of ophidian paramyxovirus (OPMV) isolated from an Aruba Island rattlesnake. Lungs from one non-infected and three mock-infected Aruba Island rattlesnakes were examined also. From 4 to 22 days following intratracheal inoculation, progressive microscopic changes were seen in the lung. Initially, increased numbers of heterophils were observed in the interstitium followed by proliferation and vacuolation of epithelial cells lining faveoli. The changes appeared to progress from cranial to caudal portions of the respiratory lung following inoculation. Beginning at 4 days postinoculation, viral antigen was demonstrated in epithelial cells lining faveoli with an immunofluorescent technique using a rabbit anti-AIV polyclonal antibody. Electron microscopy revealed loss of type I cells, hyperplasia of type II cells, and interstitial infiltrates of heterophils and mononuclear cells. Viral nucleocapsid material was seen within the cytoplasm and mature virus was seen budding from cytoplasmic membranes of infected type I and type II cells from 8 to 19 days after infection. A virus consistent with AIV was isolated from lung tissues of infected rattlesnakes, thus fulfilling Koch's postulates.     

Specificity and determinants of Sam68 RNA binding. Implications for the biological function of K homology domains

Sam68, a specific target of the Src tyrosine kinase in mitosis, possesses features common to RNA-binding proteins, including a K homology (KH) domain. To elucidate its biological function, we first set out to identify RNA species that bound to Sam68 with high affinity using in vitro selection. From a degenerate 40-mer pool, 15 RNA sequences were selected that bound to Sam68 with Kd values of 12-140 nM. The highest affinity RNA sequences (Kd approximately 12-40 nM) contained a UAAA motif; mutation to UACA abolished binding to Sam68. Binding of the highest affinity ligand, G8-5, was assessed to explore the role of different regions of Sam68 in RNA binding. The KH domain alone did not bind G8-5, but a fragment containing the KH domain and a region of homology within the Sam68 subgroup of KH-containing proteins was sufficient for G8-5 binding. Deletion of the KH domain or mutation of KH domain residues analogous to loss-of-function mutations in the human Fragile X syndrome gene product and the Caenorhabditis elegans tumor suppressor protein Gld-1 abolished G8-5 binding. Our results establish that a KH domain-containing protein can bind RNA with specificity and high affinity and suggest that specific RNA binding is integral to the functions of some regulatory proteins in growth and development.     

Staphylococcal enterotoxin A-induced fever is associated with increased circulating levels of cytokines in rabbits

Rabbits were injected intravenously with 10 to 100 ng of staphylococcal enterotoxin A (SEA) per kg, and colonic temperatures were monitored. The febrile responses were compared with circulating levels of interferon (IFN), tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, and IL-6 just before the injection of SEA. Both colonic temperatures and circulating levels of IFN, TNF, and IL-2 started to rise at 1 to 2 h and reached their peak levels at 3 to 5 h after SEA injection. Both the fever and the increased circulating levels of IFN, TNF, and IL-2 produced by SEA were decreased by pretreatment with indomethacin (a cyclo-oxygenase inhibitor) (15 mg/kg, intraperitoneally), anisomycin (a protein synthesis inhibitor) (15 mg/kg, subcutaneously), or dexamethasone (an effective anti-inflammatory and immunosuppressive agent) (4 mg/kg, intravenously) in rabbits. Rabbits were injected intravenously with 30 ng of SEA per kg on four consecutive days, and colonic temperatures were monitored. Compared to rabbits that received the single injection of SEA, rabbits that received four consecutive injections of SEA showed a lesser increase in circulating levels of IFN, TNF, and IL-2 as well as colonic temperatures in response to an intravenous dose of SEA (30 ng/kg). The data suggest that the prevention of the febrile response elicited by SEA by indomethacin, anisomycin, or dexamethasone is due to prevention by these compounds of the increase in the circulating levels of IFN, TNF, and IL-2. The pyrogenic hyporesponsiveness to repeated injection of SEA is associated with decreased production of these circulating cytokines.     

Cloning and functional characterisation of two novel nicotinic acetylcholine receptor alpha subunits from the insect pest Myzus persicae

Nicotinic acetylcholine receptors play a major role in excitatory neurotransmission in insect CNSs and constitute an important target for insecticides. Here, we report the isolation and functional characterisation of two cDNAs encoding nicotinic acetylcholine receptor alpha subunits from a major insect pest, the peach-potato aphid Myzus persicae. These two subunits, termed Mp alpha1 and Mp alpha2, are respective structural homologues of the Drosophila D alpha2/Schistocerca gregaria alphaL1 alpha-subunit pair and the Drosophila ALS alpha subunit. Xenopus oocyte expression confirmed that each Myzus subunit can form functional acetylcholine- or nicotine-gated channels. However, some electrophysiological and pharmacological properties of the Myzus subunits were distinct from those encoded by the corresponding Drosophila subunits. Coexpression of the Myzus subunits with the chick beta2 subunit revealed other differences from the Drosophila system, as only very limited potentiation of agonist-induced currents was observed with Mp alpha2 and none with Mp alpha1. Available data therefore indicate that structurally homologous insect nicotinic acetylcholine receptor alpha subunits from different species can exhibit distinctive physiological and pharmacological characteristics.     

Involvement of interleukin-3 in delayed-type hypersensitivity

The in vivo functions of interleukin-3 (IL-3) were investigated by generating IL-3-deficient mice. Although hematopoiesis was unimpaired in homozygous mutant animals, contact hypersensitivity reactions were compromised. IL-3 was required for efficient priming of hapten-specific contact hypersensitivity responses, but was dispensable for T-cell-dependent sensitization to tumor cells. These findings reveal a critical role for IL-3 in some forms of delayed-type hypersensitivity.