Effectiveness of liposomes possessing surface-linked recombinant B subunit of cholera toxin as an oral antigen delivery system

Liposomes appear to be a promising oral antigen delivery system for the development of vaccines against infectious diseases, although their uptake efficiency by Peyer's patches in the gut and the subsequent induction of mucosal immunoglobulin A (IgA) responses remain a major concern. Aiming at targeted delivery of liposomal immunogens, we have previously reported the conjugation via a thioether bond of the GM1 ganglioside-binding subunit of cholera toxin (CTB) to the liposomal outer surface. In the present study, we have investigated the effectiveness of liposomes containing the saliva-binding region (SBR) of Streptococcus mutans AgI/II adhesin and possessing surface-linked recombinant CTB (rCTB) in generating mucosal (salivary, vaginal, and intestinal) IgA as well as serum IgG responses to the parent molecule, AgI/II. Responses in mice given a single oral dose of the rCTB-conjugated liposomes were compared to those in mice given one of the following unconjugated liposome preparations: (i) empty liposomes, (ii) liposomes containing SBR, (iii) liposomes containing SBR and coadministered with rCTB, and (iv) liposomes containing SBR plus rCTB. Three weeks after the primary immunization, significantly higher levels of mucosal IgA and serum IgG antibodies to AgI/II were observed in the rCTB-conjugated group than in mice given the unconjugated liposome preparations, although the latter mice received a booster dose at week 9. The antibody responses in mice immunized with rCTB-conjugated liposomes persisted at high levels for at least 6 months, at which time (week 26) a recall immunization significantly augmented the responses. In general, mice given unconjugated liposome preparations required one or two booster immunizations to develop a substantial anti-AgI/II antibody response, which was more prominent in the group given coencapsulated SBR and rCTB. These data indicate that conjugation of rCTB to liposomes greatly enhances their effectiveness as an antigen delivery system. This oral immunization strategy should be applicable for the development of vaccines against oral, intestinal, or sexually transmitted diseases.     

A shock reaction from insect bites in patients with urticaria pigmentosa

The examination of 11 urticaria pigmentosa (UP) patients included allergological history, skin prick, scarification tests and intracutaneous tests with noninfectious and bee poison allergens, total and specific serum IgE measurements, in vitro reaction of histamine release from peripheral blood basophils induced by bee poison. The response of mastocytosis patients to insect sting was characterized by a rapid (within 5 min) development of severe systemic reactions or shock. The skin reactions and serum antibodies to bee poison were not registered in 9 of 11 patients. They also had a negative reaction of allergen-specific histamine release from basophils. This gives evidence for nonimmunological, pseudoallergic mechanism of the shock reaction. The latter can be prevented by bee poison immunotherapy. IgE-antibody-mediated allergic reaction to bee sting could not be excluded in 2 patients. For them specific immunotherapy with bee poison, possibly with purified poison preparations containing the allergens alone, are indicated.     

Design considerations for a hardware-refreshed memory card for the MC68000

Circuit complexity is the main disadvantage of using hardware rather than software to refresh dynamic RAM. Program overheads, withdrawal of interrupts from use, and increased demands on system components other than the microprocessor militate against the software solution. A hardware-refreshed 256 kbyte dynamic RAM card has been developed for use with 68000-based systems. The design includes a TMS 4500AML controller and a TMS 4164 64k dynamic RAM. The operation of the dynamic RAM is explained. The RAM is interfaced to the 68000 by the system's VME bus. The organization of the memory is discussed, and the steps in a software routine to test blocks of memory are outlined.     

A Model to Estimate the Delivered Doses of Substances in Liquid and Gaseous Phases

A conceptual model is presented for assessing the dose of a chemical substance delivered to individual lung cells when exposure can occur through inhalation of the substance as either a gas or an aerosol of droplets. Assuming a threshold value for the concentration of a toxic species in a single cell, the model shows that the physical state of the substance may affect its biologic activity. Exposure to aerosol droplets of an irritating or reactive substance will deliver much higher surface concentrations to single cells than will a similar exposure to a gas. Under certain conditions, the surface concentration can be between 100 and 10¹0; times higher when the exposure involves an aerosol. Indirect support for the model is found in the observations that threshold limit values for aerosols are generally lower than those for gases.     

Genetic mapping of the spinocerebellar ataxia type 2 gene on human chromosome 12

The dominant spinocerebellar ataxias are a genetically heterogeneous group of diseases leading to premature death of neurons in the cerebellum and other parts of the nervous system. The mutation causing SCA1 is on human chromosome (CHR) 6p and SCA3 is on CHR 14q. To refine the location of the SCA2 gene on CHR 12q, we performed genetic linkage analysis between the SCA2 locus and nine Ioci (D12S58, D12S78, D12S317, D12S330, D12S353, D12S84, D12S105, D12S79, and PLA2) in three SCA2 families. The highest pairwise lod scores were obtained between SCA2 and D12S84/D12S105 and D12S79. We determined the best order and genetic distances among these loci in ten multigenerational families by multipoint linkage analysis and established the following order: D12S101-D12S58/IGF1- D12S78-D12S317-D12S330/D12S353-D12S84/D 12S105-D12S79-PLA2. Using this genetic map, multipoint linkage analysis placed SCA2 between D12S84/D12S105 and D12S79.