We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorfieri, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorfieri in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols.

Two hours after the goldfish optic tract was cut, the severed axons in the retinal stump of the tract showed ballooning of the axoplasm and myelin sheath in the region of the cut, with accumulation in the swollen axon of various organelles, including dense cored vesicles. By day 1 the myelin sheath had degenerated back to a node of Ranvier and the tip of the severed axon had formed a myelin-free terminal bulb with a well-organized core of 9-10 nm filaments. By 2 days, such terminal bulbs were often seen to be extended on a neck of cytoplasm a few micrometers in length, presumably indicating axonal outgrowth. In addition, occasional small bundles of axon sprouts were first seen at this time. The sprouts had a diameter of about 2 micrometers and contained a central core of 9-10 nm filaments surrounded by a mantle of cell organelles (smooth endoplasmic reticulum, mitochondria and diverse vesicles), with few if any microtubules. Sprouts within a bundle were separated by fairly uniform 10-15 nm spaces. Beginning at 3 days, significant numbers of microtubules appeared in the sprouts, and there was an increasing proportion of small diameter (greater than or equal to 0.3 micrometer) sprouts. Thus it was not until 3 days that the sprouts took on the appearance usually considered to be typical of regenerating axons. By 6 days a dense layer of glial cells or macrophages formed a cap over the cut surface of the tract. Penetrating this layer were bundles containing up to 20-30 axon sprouts and also single axons which may have been serving as 'pioneering' fibres to which later-emerging axons would attach. There was no evidence that the regenerating axons were guided by the glial cells. At 6 days astroglia began to separate individual axons within the bundles but oligodendrocytes were still inactive at this time.

The malarial parasite dramatically alters its host cell by exporting and targeting proteins to specific locations within the erythrocyte. Little is known about the mechanisms by which the parasite is able to carry out this extraparasite transport. The fungal metabolite brefeldin A (BFA) has been used to study the secretory pathway in eukaryotes. BFA treatment of infected erythrocytes inhibits protein export and results in the accumulation of exported Plasmodium proteins into a compartment that is at the parasite periphery. Parasite proteins that are normally localized to the erythrocyte membrane, to nonmembrane bound inclusions in the erythrocyte cytoplasm, or to the parasitophorous vacuolar membrane accumulate in this BFA-induced compartment. A single BFA-induced compartment is detected per parasite and the various exported proteins colocalize to this compartment regardless of their final destinations. Parasite membrane proteins do not accumulate in this novel compartment, but accumulate in the endoplasmic reticulum (ER), suggesting that the parasite has two secretory pathways. This alternate secretory pathway is established immediately after merozoite invasion and at least some dense granule proteins also use the alternate pathway. The BFA-induced compartment exhibits properties that are similar to the ER, but it is clearly distinct from the ER. We propose to call this new organelle the secondary ER of apicomplexa. This ER-like organelle is an early, if not the first, step in the export of Plasmodium proteins into the host erythrocyte.