For over 80 years now, Shigella dysenteriae 1 has been known to produce one of the most potent of the lethal microbial toxins. It was originally called Shiga toxin (after the discoverer of the organism, K. Shiga) and classified as a neurotoxin because it results in a delayed-onset limb paralysis terminating in death when parenterally administered to sensitive animals (reviewed in reference 1). Shigella toxin is also cytotoxic to certain tissue culture cells, as well as enterotoxic (results in fluid secretion) when applied to intestinal mucosa (2-5). Biochemical and immunological evidence indicate that the three biological activities are the properties of the same molecule (3, 5). Its role in the pathogenesis of shigellosis has always been controversial, in part because other species of the genus could not be shown to produce the same toxin. This argument is no longer valid, for both S. flexneri and S. sonnei have been found to produce shigella toxin under appropriate in vitro conditions, and convalescent patients develop an antibody that neutralizes the dysenteriae 1 toxin (6-8). Pathogenic bacteria of other genera have also been found to produce a similar toxin that is neutralized by antibody to shigella toxin. These organisms include a variety ofE. coli serotypes including human enteropathogenic strains, the causative strain of human hemorrhagic colitis (Escherichia coli 0:155), the noninvasive rabbit pathogen RDEC-1, human Salmonella strains, and even Vibrio cholerae (9-11). The cross-reactive toxin has been dubbed "Shiga-like toxin." Since these E. coli strains do not produce the well-known LT or ST toxins and since a mutant strain of V. cholerae deleted of the gene for the production of the ADP-ribosyl transferase enzyme subunit A of cholera toxin (12) causes diarrhea in humans, the shigella (or Shiga-like) toxin may well be a critical virulence factor in diarrheal disease.Because of these observations, there is great interest in this toxin and the immunologically related products of other organisms. Shigeila toxin has recently (9-15) been purified and partially characterized by several laboratories. The

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Because PEN110 was as effective as gamma irradiation at inhibiting WBC proliferation, PEN110 treatment could potentially be used to prevent the development of GVHD following transfusion.

SUMMARY The human enteric protozoan, Giardia lamblia, has surface membrane lectin activity which mediates parasite adherence to erythrocytes. To determine whether an intestinal binding site exists for this lectin we have studied the interaction in vitro between axenically cultured Giardia trophozoites and isolated rat intestinal epithelial cells. Scanning electron microscopy showed that Giardia attached to the apical microvillus membrane and basolateral membrane of rat enterocytes. Any location on the parasite surface could mediate attachment without predeliction for the ventral disc. Trophozoites attached more avidly to jejunal compared with colonic epithelial cells. Attachment was inhibited at 4°C, by sugars and glycoproteins containing D-mannosyl residues and by subagglutinating concentrations of anti-Giardia rabbit serum and two monoclonal antibodies, all with reactivity to parasite surface membrane determinants. Trypsinisation of trophozoites also reduced attachment but the ability to attach was rapidly restored after returning trophozoites to TYI-S culture medium for 4 h at 37°C. Attachment was unaltered by the presence of the microfilament inhibitor cytochalasin B and in the absence of Ca++ and Mg++ ions. These findings support previous work that Giardia possesses a surface membrane mannose binding lectin and indicate that appropriate binding sites are present on rat intestinal epithelial cells. This lectin may play a part in mediating adherence of Giardia to mammalian intestine and could be a target for host immune defence.Adherence of microbial enteropathogens to host intestinal epithelium is considered to be a critical step in the pathogenesis of many intestinal infections.' Giardia is commonly found in close proximity to the small intestinal mucosa and when in the ventral surface down position, it is generally considered that the parasite attaches to intestinal epithelial cells by either a suction force generated beneath the ventral disc by the propulsive efforts of the ventral flagella (hydrodynamic theory),' by mechanical processes related to contractile protein elements of the ventral disc and ventrolateral flange," or by a combination of the two mechanisms.Giardia may be found in other orientations with respect to the gut mucosa such as the dorsal surface down position' as seen in one of our patients (Fig. 1). This suggests that parasite surface membrane determinants may also be involved in the attachment process. We have shown previously using mammalian erythrocytes as a model target for attachment, that Giardia lamblia, like some bacteria and other protozoa, has lectin activity associated with its surface membrane with specificities for D-glucosyl and D-mannosyl residues.7 To discover the possible relevance of this attachment mechanism in the pathogenesis of giardiasis, we have now investigated the interaction between Giardia and isolated mammalian intestinal epithelial cells to determine whether an intestinal receptor exists for this putative lectin in gut epithelium.

The levels of glucosamine and galactosamine were determined in conidia, germinating conidia, and vegetative mycelia of Neurospora crassa. In the vegetative mycelia about 90% of the amino sugars were shown to be components of the cell wall. The remaining 10% of the amino sugars were tentatively identified as the nucleotide sugars uridine diphospho-2-acetamido-2-deoxy-D-glucose and uridine diphospho-2-acetamido-2-deoxy-D-galactose. Conidia and vegetative mycelia contained about the same levels of glucosamine. During the first 9 h after the initiation of germination, the total glucosamine content had increased 3.1-fold, whereas the residual dry weight of the culture had increased 7.7-fold. This led to a drop in the glucosamine concentration from 100 Amol/g of residual dry weight to 42 ,mol/g. During this time, all of the conidia had germinated and