Area postrema lesions attenuate LiCl-induced c-Fos expression correlated with conditioned taste aversion learning

Lesions of the area postrema (AP) block many of the behavioral and physiological effects of lithium chloride (LiCl) in rats, including formation of conditioned taste aversions (CTAs). Systemic administration of LiCl induces c-Fos immunoreactivity in several brain regions, including the AP, nucleus of the solitary tract (NTS), lateral parabrachial nucleus (latPBN), supraoptic nucleus (SON), paraventricular nucleus (PVN), and central nucleus of the amygdala (CeA). To determine which of these brain regions may be activated in parallel with the acquisition of LiCl-induced CTAs, we disrupted CTA learning in rats by ablating the AP and then quantified c-Fos-positive cells in these brain regions in sham- and AP-lesioned rats 1 h following LiCl or saline injection. Significant c-Fos induction after LiCl was observed in the CeA and SON of AP-lesioned rats, demonstrating activation independent of an intact AP. LiCl-induced c-Fos was significantly attenuated in the NTS, latPBN, PVN and CeA of AP-lesioned rats, suggesting that these regions are dependent on AP activation. Almost all of the lesioned rats showed some damage to the subpostremal NTS, and some rats also had damage to the dorsal motor nucleus of the vagus; this collateral damage in the brainstem may have contributed to the deficits in c-Fos response. Because c-Fos induction in several regions was correlated with magnitude of CTA acquisition, these regions are implicated in the central mediation of lithium effects during CTA learning.     

Multi-valent human monoclonal antibody preparation against Pseudomonas aeruginosa derived from transgenic mice containing human immunoglobulin loci is protective against fatal pseudomonas sepsis caused by multiple serotypes

Pseudomonas aeruginosa is a serious human pathogen in a variety of patient groups including those with burns, hospitalized in intensive care, cystic fibrosis and neutropenia. Since there is no vaccine available, passive antibody prophylaxis against protective epitopes is an alternative strategy to prevent P. aeruginosa infection. However, immunoglobulin derived from multiple donors has variable anti-pseudomonas antibody titers, and human Mab are difficult to make from patient samples. We previously reported the use of XenoMouse mice, Ig-inactivated transgenic mice reconstituted with human immunoglobulin loci, to generate human Mab against a single serotype of P. aeruginosa lipopolysaccharide O-specific side chain (PS). We now report the creation of a panel of anti-PS human IgG2 Mab against nine additional O-specific side chain P. aeruginosa serotypes. The majority of the Mab were highly opsonic for uptake and killing of homologous P. aeruginosa by human PMN in the presence of human complement, and all the Mab protected cyclophosphamide-induced neutropenic mice from fatal P. aeruginosa sepsis with homologous serotypes. DNA sequence analysis showed that the Mab used V(H)3, V(H)4, V(H)5 and V(H)6 and Vkappa2, 3 and 4 variable region genes consistent with the heterogeneity of P. aeruginosa LPS O-side chain structure. We conclude that human Mab made in these transgenic mice against common pathogenic serotypes of P. aeruginosa are opsonic and highly protective, and that a high titer, multi-valent human Mab preparation against the majority of circulating O-side chain serotypes of P. aeruginosa could be used as prophylaxis against invasive infections in selected patient groups.     

Fully human IgG and IgM antibodies directed against the carcinoembryonic antigen (CEA) Gold 4 epitope and designed for radioimmunotherapy (RIT) of colorectal cancers

Background  

Human monoclonal antibodies (MAbs) are needed for colon cancer radioimmunotherapy (RIT) to allow for repeated injections. Carcinoembryonic antigen (CEA) being the reference antigen for immunotargeting of these tumors, we developed human anti-CEA MAbs.     

Primary HIV-1 subtype C infection in Ethiopia

Between 1997 and 2001, 1624 Ethiopian factory workers were enrolled in prospective HIV-1 cohorts in Ethiopia, at Akaki and Wonji towns. HIV-1 seroprevalence at intake was 11.8% (Akaki) and 7.1% (Wonji). HIV-1 incidence was .75 per 100 person-years (Akaki) and .35 per 100 person-years (Wonji). During follow up, CD4 T-cell counts remained significantly lower and CD8 T-cell counts significantly higher in Ethiopian seroconverters compared with Dutch seroconverters. Viral loads were lower in Ethiopian seroconverters versus Dutch seroconverters in the first months after seroconversion, subsequently increasing to similar levels. All 20 Ethiopian seroconverters were infected with HIV-1 subtype C (15 with sub-cluster C' and 5 with sub-cluster C). Viral loads were higher in sub-cluster C'-infected Ethiopian seroconverters. One subject demonstrated a window period of at least 204 days, combined with a high preseroconversion viral load and no decline of CD4 T cells over a follow-up period of at least 3 years.     

Distribution of Lymphocyte Subsets in Healthy Human Immunodeficiency Virus-Negative Adult Ethiopians from Two Geographic Locales

Immunological values for 562 factory workers from Wonji, Ethiopia, a sugar estate 114 km southeast of the capital city, Addis Ababa, Ethiopia, were compared to values for 218 subjects from Akaki, Ethiopia, a suburb of Addis Ababa, for whom partial data were previously published. The following markers were measured: lymphocytes, T cells, B cells, NK cells, CD4⁺ T cells, and CD8⁺ T cells. A more in depth comparison was also made between Akaki and Wonji subjects. For this purpose, various differentiation and activation marker (CD45RA, CD27, HLA-DR, and CD38) expressions on CD4⁺ and CD8⁺ T cells were studied in 60 male, human immunodeficiency virus-negative subjects (30 from each site). Data were also compared with Dutch blood donor control values. The results confirmed that Ethiopians have significantly decreased CD4⁺ T-cell counts and highly activated immune status, independent of the geographic locale studied. They also showed that male subjects from Akaki have significantly higher CD8⁺ T-cell counts, resulting in a proportional increase in each of the CD8⁺ T-cell compartments studied: naïve (CD45RA⁺CD27⁺), memory (CD45RA⁻CD27⁺), cytotoxic effector (CD45RA⁺CD27⁻), memory/effector (CD45RA⁻CD27⁻), activated (HLA-DR⁺CD38⁺), and resting (HLA-DR⁻CD38⁻). No expansion of a specific functional subset was observed. Endemic infection or higher immune activation is thus not a likely cause of the higher CD8 counts in the Akaki subjects. The data confirm and extend earlier observations and suggest that, although most lymphocyte subsets are comparable between the two geographical locales, there are also differences. Thus, care should be taken in extrapolating immunological reference values from one population group to another.     

Improving Doctor–Patient Communication: Examining Innovative Modalities Vis-à-vis Effective Patient-Centric Care Management Technology

This analysis investigates what patients and practitioners can do to improve their interactive communications to achieve optimal patient-centric (PC) care. One goal of this clinical practice approach is to improve patient satisfaction, compliance, and outcomes. The mutual responsibilities required of both the patients and practitioners to attain PC care are discussed. Innovative, information technology techniques in the healthcare environment in general and in care delivery in particular are explored. Practitioner-to-patient encouragement vis-à-vis self education on their conditions is also provided.