No abstract

Intrastriatal injections of qn c acid induce a pattern of neuronal degeneration similr to that seen in Huntington disease. In the present study, nerve growth factor (NGF) crossed the blo-brain barrier in a dose-dependent fashion following intravenous infusion when conjugated to an antibody directed against the transferrin receptor (9). In this regard, striatal cholinergic interneurons express the low-affinity p75 NGF receptor during development and the high-affinity TrkA NGF receptor throughout their lifetime, indicating that these neurons can respond to NGF (10-13).Whereas trophic factors such as NGF may be powerful tools for modulating the function and survival of specific neuronal populations, their clinical utility is limited by their inability to cross the blood-brain barrier. As a result, administration of neurotrophic factors to the central nervous system (CNS) requires invasive neurosurgical procedures such as infusion into the ventricular space (14), directly into brain parenchyma (15), or grafting neurotrophin-producing cells into CNS sites (16-18).To develop a noninvasive system for the delivery of macromolecules to the brain, Friden et al. (19,20) showed that NGF crosses the blood-brain barrier when conjugated to an antibody directed against the transferrin receptor (TfR). This delivery system takes advantage of the endogenous transport mechanism responsible for the delivery of iron to the brain and the fact that capillary endothelial cells within the brain express a high density of TfR (19,21 (19,20). Intravenous injections of OX-26-NGF conjugate (20 pg of NGF per injection; n = 12 rats), a nonconjugated mixture of OX-26 and NGF that was identical in composition to the conjugate (20 .g of NGF per injection; n = 8 rats), or vehicle (0.1 M sodium phosphate/5 mM EDTA, pH 6.0; n = 9 rats) were made through a jugular catheter in 0.5-ml volumes and the injections were flushed with 0.3 ml of heparinized saline. Intravenous injections were made for two consecutive days prior to a unilateral intrastriatal infusion of 120 nmol of quinolinic acid, the day of the lesion, and on alternate days thereafter for 14 days. Occasionally, the jugular catheter became occluded. Under these conditions, the rats received their injection via the tail vein.Quinolinic Acid Lesion Model. Young adult male SpragueDawley rats (200-300 g) were used in this study. Rats were first anesthetized with sodium pentobarbital (15 mg/kg, i.p.) and a PE10 (Clay Adams) catheter was placed into the left jugular vein. Three days later, rats were reanesthetized with sodium pentobarbital (15 mg/kg, i.p.) and placed in a Kopf stereotaxic frame. Quinolinic acid (120 nmol) was dissolved and sonicated in 0.9%6 NaCl and was drawn up into a 10-/4Hamilton syringe fitted with a sharp-tipped 26-gauge needle. The Hamilton syringe was lowered into the striatum at the following coordinates: 0.8 mm anterior to bregma; 2.5 mm

The etiological agent of 'bumper car' disease in lobsters Homarus americanus is described as a new species of ciliate, Anophryoides haemophila (Scuticociliatida: Orchitophryidae). A. haemophila n, sp, is distinguished from other species in the genus by the curved rectangular oral polykinetid 2, a somatic kinety range of 16 to 18, and its relatively small size. The parasite is easy to maintain in vivo and in vitro for extended periods at 2 to 5°C. Apparently the ciliate can be a significant impediment to the economic viability of coldwater lobster impoundments in eastern North America. However, factors inducing epizootics of 'bumper car' disease are unknown.

Studies were undertaken to characterize and determine the pathogenic mechanisms involved in a newly described systemic disease in Homarus americanus (American lobster) caused by a Vibrio fluvialis-like microorganism. Nineteen isolates were obtained from eight of nine lobsters sampled. Biochemically, the isolates resembled V. fluvialis, and the isolates grew optimally at 20°C; none could grow at temperatures above 23°C. The type strain (1AMA) displayed a thermal reduction time (D value) of 5.77 min at 37°C. All of the isolates required at least 1% NaCl for growth. Collectively, the data suggest that these isolates may embody a new biotype. Pulsed-field gel electrophoresis (PFGE) analysis of the isolates revealed five closely related subgroups. Some isolates produced a sheep hemagglutinin that was neither an outer membrane protein nor a metalloprotease. Several isolates possessed capsules. The isolates were highly susceptible to a variety of antibiotics tested. However, six isolates were resistant to erythromycin. Seventeen isolates harbored plasmids. Lobster challenge studies revealed that the 50% lethal dose of a plasmid-positive strain was 100-fold lower than that of a plasmid-negative strain, suggesting that the plasmid may enhance the pathogenicity of these microorganisms in lobsters. Microorganisms that were recovered from experimentally infected lobsters exhibited biochemical and PFGE profiles that were indistinguishable from those of the challenge strain. Tissue affinity studies demonstrated that the challenge microorganisms accumulated in heart and midgut tissues as well as in the hemolymph. Culture supernatants and polymyxin B lysates of the strains caused elongation of CHO cells in tissue culture, suggesting the presence of a hitherto unknown enterotoxin. Both plasmid-positive and plasmid-negative strains caused significant dose-related intestinal fluid accumulations in suckling mice. Absence of viable organisms in the intestinal contents of mice suggests that these microorganisms cause diarrhea in mice by intoxication rather than by an infectious process. Further, these results support the thermal reduction data at 37°C and suggest that the mechanism(s) that led to fluid accumulation in mice differs from the disease process observed in lobsters by requiring neither the persistence of viable microorganisms nor the presence of plasmids. In summary, results of lobster studies satisfy Koch's postulates at the organismal and molecular levels; the findings support the hypothesis that these V. fluvialis-like organisms were responsible for the originally described systemic disease, which is now called limp lobster disease.Catastrophic losses of Homarus americanus (American lobster) have been most consistently associated with gaffkemia, a disease caused by Aerococcus viridans subsp. homari (52,59). Recognized more than half a century ago as a cause of heavy mortalities in natural populations and impounded lobsters on the east coast of North America, infection usually results when A. viridans breaches the integu...