Demonstration that a lectin-like receptor (gp90MEL) directly mediates adhesion of lymphocytes to high endothelial venules of lymph nodes.

Lymphocyte migration from the blood into most secondary lymphoid organs is initiated by a highly selective adhesive interaction with the endothelium of specialized blood vessels known as high endothelial venules (HEV). The propensity of lymphocytes to migrate to particular lymphoid organs is known as lymphocyte homing, and the receptors on lymphocytes that dictate interactions with HEV at particular anatomical sites are designated "homing receptors". Based upon antibody blockade experiments and cell-type distribution studies, a prominent candidate for the peripheral lymph node homing receptor in mouse is the approximately 90-kD cell surface glycoprotein (gp90MEL) recognized by the monoclonal antibody MEL-14. Previous work, including sequencing of a cDNA encoding for this molecule, supports the possibility that gp90MEL is a calcium-dependent lectin-like receptor. Here, we show that immunoaffinity-purified gp90MEL interacts in a sugar-inhibitable manner with sites on peripheral lymph node HEV and prevents attachment of lymphocytes. Lymphocyte attachment to HEV in Peyer's patches, a gut-associated lymphoid organ, is not affected by gp90MEL. The results demonstrate that gp90MEL, as a lectin-like receptor, directly bridges lymphocytes to the endothelium

A homing receptor-IgG chimera as a probe for adhesive ligands of lymph node high endothelial venules.

The binding of lymphocytes to high endothelial venules (HEV) within peripheral lymph nodes (pln) is thought to be mediated by a lectinlike adhesion molecule termed the pln homing receptor (pln HR). The cloning and sequencing of cDNAs encoding both murine and human pln HR revealed that these adhesion molecules contain protein motifs that are homologous to C-type or calcium dependent lectin domains as well as to epidermal growth factor (egf) and complement-regulatory protein domains. We have produced a novel, antibody-like form of the murine HR by joining the extracellular region of the receptor to a human IgG heavy chain. This antibody-like molecule is capable of recognizing carbohydrates, blocking the binding of lymphocytes to pln HEV, and serving as a histochemical reagent for the staining of pln HEV. This murine HR-IgG chimera should prove useful in analyzing the distribution of the HR ligand(s) in normal as well as in inflammatory states

Barriers to initiation of antiretroviral treatment in rural and urban areas of Zambia: a cross-sectional study of cost, stigma, and perceptions about ART

BACKGROUND: While the number of HIV-positive patients on antiretroviral therapy (ART) in resource-limited settings has increased dramatically, some patients eligible for treatment do not initiate ART even when it is available to them. Understanding why patients opt out of care, or are unable to opt in, is important to achieving the goal of universal access. METHODS: We conducted a cross-sectional survey among 400 patients on ART (those who were able to access care) and 400 patients accessing home-based care (HBC), but who had not initiated ART (either they were not able to, or chose not to, access care) in two rural and two urban sites in Zambia to identify barriers to and facilitators of ART uptake. RESULTS: HBC patients were 50% more likely to report that it would be very difficult to get to the ART clinic than those on ART (RR: 1.48; 95% CI: 1.21-1.82). Stigma was common in all areas, with 54% of HBC patients, but only 15% of ART patients, being afraid to go to the clinic (RR: 3.61; 95% CI: 3.12-4.18). Cost barriers differed by location: urban HBC patients were three times more likely to report needing to pay to travel to the clinic than those on ART (RR: 2.84; 95% CI: 2.02-3.98) and 10 times more likely to believe they would need to pay a fee at the clinic (RR: 9.50; 95% CI: 2.24-40.3). In rural areas, HBC subjects were more likely to report needing to pay non-transport costs to attend the clinic than those on ART (RR: 4.52; 95% CI: 1.91-10.7). HBC patients were twice as likely as ART patients to report not having enough food to take ART being a concern (27% vs. 13%, RR: 2.03; 95% CI: 1.71-2.41), regardless of location and gender. CONCLUSIONS: Patients in home-based care for HIV/AIDS who never initiated ART perceived greater financial and logistical barriers to seeking HIV care and had more negative perceptions about the benefits of the treatment. Future efforts to expand access to antiretroviral care should consider ways to reduce these barriers in order to encourage more of those medically eligible for antiretrovirals to initiate care

Lost but Not Forgotten—The Economics of Improving Patient Retention in AIDS Treatment Programs

Gregory Bisson and Jeffrey Stringer discuss the implications of a new study showing how loss to follow-up affects the effectiveness of a public sector HIV program in Côte d'Ivoire

Short and long term retention in antiretroviral care in health facilities in rural Malawi and Zimbabwe.

Despite the successful scale-up of ART services over the past years, long term retention in ART care remains a major challenge, especially in high HIV prevalence and resource-limited settings. This study analysed the short (<12 months) and long (>12 months) term retention on ART in two ART programmes in Malawi (Thyolo district) and Zimbabwe (Buhera district)

Adenosquamous carcinoma of breast in a 19 years old woman: a case report

<p>Abstract</p> <p>Background</p> <p>Adenosquamous carcinoma of the breast is a rare form of metaplastic breast carcinoma. We report such a case in a 19 years old female.</p> <p>Case presentation</p> <p>Case notes and histopathology were reviewed. Adenosquamous carcinoma was diagnosed on wide local excision and patient underwent skin-sparing mastectomy with Latissimus dorsi flap reconstruction.</p> <p>Conclusions</p> <p>Adenosquamous carcinoma of the breast is a rare form of metaplastic breast carcinoma. Data on correct management, follow-up and prognosis are very limited but given the high potential for local recurrence, aggressive surgery may be the only option.</p

Cerebellar Integrity in the Amyotrophic Lateral Sclerosis - Frontotemporal Dementia Continuum

Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology

A portable near infrared spectroscopy system for bedside monitoring of newborn brain

BACKGROUND: Newborns with critical health conditions are monitored in neonatal intensive care units (NICU). In NICU, one of the most important problems that they face is the risk of brain injury. There is a need for continuous monitoring of newborn's brain function to prevent any potential brain injury. This type of monitoring should not interfere with intensive care of the newborn. Therefore, it should be non-invasive and portable. METHODS: In this paper, a low-cost, battery operated, dual wavelength, continuous wave near infrared spectroscopy system for continuous bedside hemodynamic monitoring of neonatal brain is presented. The system has been designed to optimize SNR by optimizing the wavelength-multiplexing parameters with special emphasis on safety issues concerning burn injuries. SNR improvement by utilizing the entire dynamic range has been satisfied with modifications in analog circuitry. RESULTS AND CONCLUSION: As a result, a shot-limited SNR of 67 dB has been achieved for 10 Hz temporal resolution. The system can operate more than 30 hours without recharging when an off-the-shelf 1850 mAh-7.2 V battery is used. Laboratory tests with optical phantoms and preliminary data recorded in NICU demonstrate the potential of the system as a reliable clinical tool to be employed in the bedside regional monitoring of newborn brain metabolism under intensive care

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well