Endothelial cell infection and thrombosis in paralysis caused by equid herpesvirus-1: Equine stroke

Summary Eight mares were infected with equid herpesvirus-1 subtype 1 isolated from a case of equine paresis. In two mares killed at 4 d.p.i. immunofluorescence showed endothelial cell infection together with thrombosis in the rete arteriosus of the nasal mucosa and also in the spinal cord of one of these mares. Circulating platelet counts in the other six mares fell as early as 2 d.p.i. and remained depressed for seven days. Circulating immune complexes started to appear at 2 d.p.i., reached maximum levels at 10 d.p.i., but were undetectable at 28 d.p.i. Three of the six remaining mares developed varying degrees of inco-ordination at 8 and 9 d.p.i. In the two inco-ordinate mares that were killed at 9 and 10 d.p.i. the haemorrhages in the spinal cord and brain were associated with extensive endothelial cell fluorescence and thrombus formation. Clinical paresis coincided with an increase in circulating complement fixing and neutralising antibodies which in all six mares were higher against the subtype 2 isolate than subtype 1.In five yearlings infected with a subtype 2 isolate of EHV-1 platelet counts remained normal and neither immune complexes nor viraemia, nor inco-ordination were detected.With 8 Figures     

Mechanical and morphological determinants of peak power output in elite cyclists

Mechanical peak power output (PPO) is a determinant of performance in sprint cycling. The purpose of this study was to examine the relationship between PPO and putative physiological determinants of PPO in elite cyclists, and to compare sprint performance between elite sprint and endurance cyclists. Thirty-five elite cyclists (18 endurance; 17 sprint) performed duplicate sprint cycling laboratory tests to establish PPO and its mechanical components. Quadriceps femoris (Q_VOL) and hamstring muscle volume (HAM_VOL) were assessed with MRI, vastus lateralis pennation angle (Pθ_VL) and fascicle length (FL_VL) were determined with ultrasound imaging, and neuromuscular activation of three muscles was assessed using EMG at PPO during sprint cycling. For the whole cohort, there was a wide variability in PPO (range 775-2025 W) with very large, positive, bivariate relationships between PPO and Q_VOL (r = .87), HAM_VOL (r = .71), and Pθ_VL (r = .81). Step-wise multiple regression analysis revealed that 87% of the variability in PPO between cyclists was explained by two variables Q_VOL (76%) and Pθ_VL (11%). The sprint cyclists had greater PPO (+61%; P < .001 vs endurance), larger Q_VOL (P < .001), and BF_VOL (P < .001) as well as more pennate vastus lateralis muscles (P < .001). These findings emphasize the importance of quadriceps muscle morphology for sprint cycling events.     

Thyroid hormone and development of the rat hippocampus: morphological alterations in granule and pyramidal cells

A quantitative study of the morphogenesis of granule and pyramidal cells was performed on Golgi-Cox preparations of the developing hippocampus of normal and hypothyroid rats, and hypothyroid rats given replacement thyroxine treatment. In the normal hippocampus, the volume of the cell body and the number of branching points on the apical and on the basal dendrites of pyramidal cells increased between 6 and 10 days after birth. The pyramidal cells of Ammon's horn showed a gradation from area CA1 to area CA4 of progressive differentiation. In thyroid-deficient rats, the arborization of the dendritic field of both granule and pyramidal cells was impaired, and for pyramidal cells the extent of the impairment depended on the position of the cells in the Ammon's horn, the cells of CA3-4 areas being the most affected. Treatment of hypothyroid rats with a physiological dose of thyroxine restored some of the morphological defects to normal, but others were altered beyond control levels, indicating that thyroid hormone differentially controls not only the measured indices of maturation but also that its influence depends on the position of the pyramidal cells. The observations were consistent with the concept that thyroid hormone is important in the establishment of the CA1 to CA4 gradient of pyramidal cell differentiation and in the development of the spatiotemporal relationship between pyramidal and granule cells of the hippocampus.     

Endotoxin protects against hyperoxic decrease in membrane fluidity in endothelial cells but not in fibroblasts

We evaluated the ability of endotoxin to protect against hyperoxic depression of plasma membrane fluidity in endothelial cells and fibroblasts in culture. Second- to-fifth passage porcine aortic endothelial cells and human newborn foreskin fibroblasts with 20 ng/ml of endotoxin or diluent in the culture medium were exposed to 20% O2 (control) or 95% O2 (hyperoxic) in 5% CO2 for 4 hours. After exposure, cells were labeled with 1,6-diphenyl-1,3,5-hexatriene (DPH), an aromatic hydrocarbon that partitions into the hydrophobic core of lipid bilayer membranes, or transparinaric acid (TPA), a natural, conjugated fatty acid that orients parallel to fatty acyl chains of membrane phospholipids. Membrane fluidity was monitored by measuring changes in the steady state fluorescence anisotropies (rs) for DPH and for TPA by using fluorescence spectroscopy. Reductions in membrane fluidity increase the value of rs. Addition of endotoxin to the culture medium of control endothelial cells and fibroblasts had no effect on rs for DPH or TPA. In hyperoxic endothelial cells, rs for DPH and rs for TPA were increased (p less than 0.001). Addition of endotoxin to the medium of hyperoxic endothelial cells prevented the increases in rs for DPH and TPA. Hyperoxia increased rs for DPH (p less than 0.003) but not rs to TPA in fibroblasts, and endotoxin failed to prevent this increase. These results indicate that hyperoxia decreases plasma membrane fluidity in endothelial cells and fibroblasts and demonstrate that endotoxin prevents the decrease in plasma membrane fluidity in endothelial cells, but not in fibroblasts. These membrane-protective effects may represent an alternative mechanism by which endotoxin protects against hyperoxic cellular injury, and this mechanism may be specific for hyperoxic injury to endothelial cells.     

Antineuron specific enolase staining reactions in sarcomas and carcinomas: its lack of neuroendocrine specificity.

A commercially available polyclonal antiserum (Dakopatts) raised against bovine neuron specific enolase (NSE) was reacted with 197 sarcomas, 32 carcinomas, 11 carcinoid tumours and 20 malignant melanomas to assess its specificity for neuroendocrine tumours. All the tumours had been fixed in formalin and embedded in paraffin. Positive tumour cells were found in two of 11 squamous cell carcinomas, one of 11 adenocarcinomas, 10 of 10 oat cell carcinomas, 11 of 11 carcinoid tumours, 16 of 20 malignant melanomas, four of seven clear cell sarcomas, nine of 25 leiomyosarcomas, four of 22 rhabdomyosarcomas, one of seven angiosarcomas and one of 20 synovial sarcomas.     

Coronary Artery Disease in Patients with Ischemic Stroke and TIA

Background and ObjectivesIschemic stroke (IS) and coronary artery disease (CAD) share common risk factors and one may be the harbinger of the other. We aimed to study prevalence of symptomatic and asymptomatic CAD in a cohort of consecutive patients with IS and assess its relationship with intracranial and extracranial large artery cerebrovascular disease (LAD).MethodsAll consecutive eligible IS and Transient Ischemic Attack (TIA) patients were recruited into the study. Both clinically suspected and asymptomatic patients (N = 259) underwent myocardial Stress-rest Gated Technetium-99m (Tc99m) MIBI Myocardial Perfusion SPECT scan performed on a dual head SPECT-CT to estimate evidence of myocardial ischemia.ResultsThree hundred patients completed the study. Forty one patients were previously diagnosed cases of definitive CAD. Twelve patients were clinically suspected to have CAD and 247 patients were asymptomatic. Among these, 12 patients (4.81%) had a positive SPECT. The overall prevalence of CAD was 17.67% (n = 53). Presence of diabetes was an independent predictor of CAD (OR 1.98, 95% CI 1.07-3.67. P .02). No significant association was found between the presence of LAD and CAD in all subgroup comparisons. However, there was a suggestion of higher LAD among patients with known CAD compared with others.ConclusionsCAD is prevalent in patients with ischemic stroke. No definitive relationship was found between CAD and intracranial or extracranial LAD. Population based stratification tools are needed to further assess the need to detect subclinical CAD in patients with stroke.     

Somatostatin receptors: identification and characterization in rat brain membranes

We have identified and characterized specific receptors for tetradecapeptide somatostatin (SRIF; somatotropin release-inhibiting factor) in rat brain using [125I]Tyr11]SRIF as the radioligand. These receptors are present in membranes obtained from a subfraction of synaptosomes. Membranes derived from cerebral cortex bind SRIF with high affinity (Ka = 1.25 X 10(10) M-1) and have a maximum binding capacity (Bmax) of 0.155 X 10(-12) mol/mg. Neither opiates nor other neuropeptides appear to influence the binding of SRIF to brain membranes. Synthetic analogs with greater biological potency than SRIF--[D-Trp8]SRIF, [D-Cys14]SRIF, and [D-Trp8, D-Cys14]SRIF--bind to the receptors with greater avidity than SRIF, whereas inactive analogs [(2H)Ala3]SRIF and [Ala6]SRIF exhibit low binding. The ratio of receptor density to endogenous somatostatin is high in the cortex, thalamus, and striatum, low in the hypothalamus, and extremely low in the brain stem and cerebellum. Thus, SRIF receptors in the brain appear to be a distinct, new class of receptors with a regional distribution different from that of endogenous somatostatin.     

Hydrogen bonding, overlap geometry, and sequence specificity in anthracycline antitumor antibiotic.DNA complexes in solution.

We have deduced structural aspects of the intercalation complex of the anthracycline antitumor antibiotic daunomycin and its analogs with the synthetic DNA poly(dA-dT) by 1H and 31P NMR in high-salt solution. We demonstrate that the base pairs are intact at the antibiotic binding site and that the anthracycline phenolic hydroxyls form intramolecular hydrogen bonds with the quinone carbonyls and are shielded from solvent in the intercalation complex. The complexation shifts of the exchangeable phenolic and nonexchangeable aromatic protons demonstrate that rings B and C of the anthracycline chromophore overlap with adjacent base pairs, while anthracycline ring D passes right through the intercalation site in the complex. We observe two resolved 31P resonances attributable to the dA-dT and dT-dA phosphodiester linkages in the phosphorus spectra of the neighbor-exclusion daunomycin.poly(dA-dT) complex. This suggests that the anthracycline antitumor antibiotic exhibits a sequence specificity in its intercalation complex with alternating purine-pyrimidine synthetic DNAs in solution. These conclusions on hydrogen bonding and overlap geometry at the intercalation site and sequence specificity for the daunomycin.poly(dA-dT) complex in solution are in agreement with the structure of the daunomycin.dC-dG-dT-dA-dC-dG hexanucleotide duplex crystalline complex at atomic resolution published recently [Quigley, G. J., Wang, A. H.-J., Ughetto, G., van der Marel, G., van Boom, J. H. & Rich, A. (1980) Proc. Natl. Acad. Sci. USA 77, 7204-7208].