Comparisons of the course of coccidioidomycosis in two strains of inbred mice established that BALB/c mice are significantly more susceptible to pulmonary infection with Coccidioides immitis than are DBA/2 mice. The susceptibility of BALB/c mice does not reside in their inability to mount a delayed-type hypersensitivity response to C. immihis antigen. That is, BALB/c mice manifested footpad hypersensitivity to coccidioidin early during the course of disease, to a level comparable to that of DBA/2 mice. In contrast to the more resistant DBA/2 mouse strain, however, BALB/c mice developed anergy by day 15 postinfection. Suppression of the delayed-type hypersensitivity response was not specific for C. immitis antigen, as evidenced by the finding that BALB/c mice immunized with mycobacterial purified protein derivative prior to infection with C. immitis were suppressed in their footpad response to mycobacterial antigen at day 15 postinfection. Taken together, these results establish that genetically determined susceptibility to this fungus is associated with an acquired suppression of cell-mediated immune reactivity. Coccidioidomycosis is a mycotic disease caused by the diphasic fungus Coccidioides immitis. Primary infection is acquired via inhalation of mycelial-phase arthroconidia, which convert to endosporulating spherules in host tissue. Manifestations of the disease range from a benign, selflimited pulmonary infection to a severe, progressive, and often fatal mycosis involving pulmonary and extrapulmonary tissues. Host defense against C. immitis is T-cell dependent, transferable by immune T cells, independent of antibody, and correlative with delayed-type hypersensitivity (DTH) to coccidioidal antigens (1-3). Thus, in humans and experimental animals, primary self-limited disease is commonly associated with strong cell-mediated immune responses to C. immitis, and conversely, progressive coccidioidomycosis is associated with depressed cell-mediated immunity (CMI)

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A novel nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]-guanine (BIOLF-62), was found to have potent antiviral activity against herpes simplex virus types 1 and 2 at concentrations well below cytotoxic levels. For example, the Patton strain of herpes simplex virus type 1 was susceptible at concentrations 140-to 2,900-fold below that which inhibited cell division by 50%, depending upon the cell line used for assay. Different herpesvirus strains varied considerably in their susceptibility to the drug, as did results obtained with the same virus strain in different cell lines. BIOLF-62 compared favorably with 5-iodo-2'-deoxyuridine and acyclovir with respect to ratios of viral to cell inhibitory drug concentrations. Patterns of drug resistance in herpesvirus mutants suggested that the primary mode of action of BIOLF-62 is different from that of known antiviral compounds. Human adenovirus type 2, varicella-zoster virus, and Epstein-Barr virus were inhibited by this drug but at concentrations within the cell inhibitory range. Vaccinia virus and human cytomegalovirus were not inhibited at high drug concentrations.

Outer membrane fractions from Bacteroides gingivalis strains ATCC 33277, 381, W50, and W83 were isolated by French pressure cell disruption and the distribution of major and minor proteins was determined by SDS-PAGE electrophoresis after treatment with 2% Sarkosyl and 2% Triton X-100. Heat-modifiability of the outer membrane proteins (OMPs) from these B. gingivalis strains was also determined after treatment at 100 degrees C and analysis by both 1- and 2-dimensional SDS-PAGE. The distribution of the OMPs on the surface of these B. gingivalis strains was determined by 125I labelling. For the most part of the OMPs of B. gingivalis presented a complex distribution, with OMPs observed between 123 kD and 13 kD. While the distribution of the OMPs was strain specific, OMPs common to all of the strains were observed. Two percent Sarkosyl treatment of the OMs at room temperature resulted in the solubilization of approximately 60% of the OMP. The Sarkosyl-insoluble MOMPs had relative molecular weights between 110 kD and 20 kD. Many of the OMPs which were separated at room temperature were heat-modified at either 65 degrees C or 100 degrees C. Heating of the OMs at 100 degrees C resulted in the heat modification of the majority of those OMPs observed at room temperature. Sarkosyl-100 degrees C OMs displayed MOMPs at apparent molecular weights between 90 kD and 15 kD. Radioiodination of the B. gingivalis strains ATCC 33277, 381, W83 and W50 revealed between 7 and 14 MOMPs at the cell surface depending upon the strain. The complexity of the OM of these B. gingivalis strains indicated the possibility of identifying and separating those OMPs involved in a variety of biological functions, including virulence, transport, and cell interaction.

Can. J . Chem. 60, 3005 (1982). The chemical synthesis of 9-[[2-hydroxy-l-(hydroxymethyl)ethoxy]methyl]guanine is described. This compound, known a s BIOLF-62, is active against herpesviruses. This compound is a member of a novel class of nucleoside analogues which lacka rigid carbohydrate ring, but which possess all of the functional groups of naturally occurring deoxynucleosides. I The search for biologically active molecules has ' focused a great deal of attention on modified nucleosides (1-3). For several years we have been i developing a nucleoside analogue structure intended to interfere with viral and bacterial systems. The I structure was designed to lack the rigid conformal tional feature (syn-anti) of natural nucleosides but i at the same time retain the essential chemical features of natural nucleosides (e.g., purine or I pyrimidine ring, 03', 0 4 ' , and Os'oxygen functionalities). In a preliminary report (4) we described the synthesis of the adenine analogue 9[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]adenine. This compound was neither a substrate nor an inhibitor for adenosine deaminase, a key enzyme in animal systems that inactivates in vivo most adenine derivatives that show promising biological activity in vitro. In this report we wish to describe the synthesis of another member of this series, the potent antiviral compound 9[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine (5) which is known as BIOLF-62. Results and discussionThe first route fully explored for the synthesis of BIOLF-62 involved the condensation of 6-chloro-I