Expression of somatostatin receptors in arginine vasopressin hormone-secreting olfactory neuroblastoma--report of two cases

OBJECTIVE: Arginine vasopressin hormone-secreting olfactory neuroblastomas are extremely rare, with fewer than twenty cases reported in the literature. Two of these cases, both initially presenting with the syndrome of inappropriate antidiuretic hormone, are presented. The second tumour was successfully identified using somatostatin receptor (octreotide) radiographic scintography. METHOD: The pathological specimens from both cases were examined immunohistochemically for somatostatin receptors. RESULTS: Samples from both cases demonstrated positivity for somatostatin receptors. CONCLUSIONS: This report demonstrates the potential use of somatastatin analogues in the investigation, follow-up and treatment of patients with olfactory neuroblastoma.     

Cortical organization of sensory corrections in visuomotor skill acquisition

During sensorimotor skill acquisition, early learning of the required neuromuscular pattern and sensorimotor mappings is followed by an intermediate stage of gradually increasing consistency and efficiency of execution, which gives way, with persistent practice, to the later stages of automatization. It has been suggested that the intermediate stage is distinguished by refinements in the background sensory corrections that support, stabilize and smoothen the fine motor adjustments required by the new coordination. While the later stages of motor refinement are thought to be sub-cortically organized, the neurophysiology of the proposed sensory learning component in the intermediate stage is not well understood. During explicit learning of a visually cued finger-tap sequence, the present research used fMRI to isolate those cortical activations that were significant in the immediate post-learning phase, but were not also observed during the corresponding pre-learning phase. Such exclusively post-learning activation occurred significantly more in visual and somatosensory association areas, than in primary somatosensory or primary and secondary motor areas. These results show that the intermediate stage of skill acquisition has a significant sensory learning component, and that the process has observable cortical correlates.     

Binding of alpha2 monoclonal antibody to human cervical tumor cell (SiHa) surface alpha2beta1 integrin modulates MMP-2 activity

OBJECTIVE(S): The purpose was to study the interrelationship between cell surface integrin receptor (alpha2beta1) and matrixmetalloproteinases. METHODS: Immunoprecipitation and cell adhesion assay were done to assay alpha2beta1 and alpha3beta1 on SiHa cell surface. Zymogram was developed to assay secreted MMP activity of cells grown in presence of alpha2 monoclonal antibody. Immunoblot was developed to assay expression of MMP-2, FAK, and p-FAK. Plasma membrane-dependent activation of MMP2 was performed by incubating pure MMP-2 with membrane-enriched fraction isolated from SiHa cells. RESULTS: Immunoprecipitation and cell adhesion assay results confirmed the presence of alpha2beta1 receptor on SiHa cells. Zymographic analysis of serum-free media collected at different time points from SiHa cells grown on alpha2 monoclonal antibody-coated culture dishes showed the expression and activation of MMP-2 within 2-4 h, confirmed by immunoblot. Western blot of cells grown on alpha2-coated dishes for 30 min-4 h showed increased phosphorylation of FAK. Membrane-enriched fraction isolated from SiHa cells was found to specifically activate proMMP-2 to its activated forms within 30 min. CONCLUSION(S): The experimental findings strongly indicate that SiHa cell surface alpha2beta1 regulates MMP-2 expression. Increased phosphorylation of focal adhesion kinase (FAK) strongly indicates the possible role of FAK in signaling cascade. Incubation of SiHa cell membrane fraction with pure MMP-2 strongly confirms the cell membrane-dependent activation of proMMP2.     

Immobility--a major risk factor for development of pressure ulcers among adult hospitalized patients: a prospective study

OBJECTIVE: To identify risk factors associated with pressure ulcer development among adult hospitalized medical and surgical patients. DESIGN: A prospective comparative study including 530 adult patients from medical and surgical wards. Registered Nurses made the data collection on admission and once a week for up to 12 weeks. The risk assessment scale used was the Risk Assessment Pressure Sore (RAPS) scale, including the following variables; general physical condition, activity, mobility, moisture, food intake, fluid intake, sensory perception, friction and shear, body temperature and serum albumin. RESULTS: Sixty-two (11.7%) patients developed 85 pressure ulcers. The most common pressure ulcer was that of nonblanchable erythema. Patients who developed pressure ulcers were significantly older, hospitalized for a longer time, had lower scores on the total RAPS scale, had lower weight and lower diastolic blood pressure than nonpressure ulcer patients did. In the multiple logistic regression analyses using variables included in the RAPS scale immobility emerged as a strong risk factor. When adding remaining significant variables in the analyses, mobility, time of hospitalization, age, surgical treatment and weight were found to be risk factors for pressure ulcer development. CONCLUSION: It is confirmed that immobility is a risk factor of major importance for pressure ulcer development among adult hospitalized patients. The results also indicate that the RAPS scale may be useful for prediction of pressure ulcer development in clinical practice.     

Splenic hydatid cysts in a 20-year-old soldier

Hydatid disease is a parasitic infection of humans and herbivorous animals caused by Echinococcus granulosus. A 20-year-old male soldier from Booshehr province police center was admitted with left upper quadrant pain that began 1 year before admission. Sonography disclosed an echogenic mass measuring 14 x 16 cm near the spleen and kidneys; a computed tomography scan confirmed it as a hypodense mass of the spleen that was 16 x 17 x 18 cm in dimension. Casoni skin test and indirect fluorescent antibody were positive. Through laparatomy, a splenectomy was successfully performed.     

Evaluation of the compatibility of a second generation recombinant anthrax vaccine with aluminum-containing adjuvants

Recombinant protective antigen (rPA) is the active pharmaceutical ingredient in a second generation anthrax vaccine undergoing pre-clinical evaluation. This rPA vaccine differs from the currently licensed vaccine, anthrax vaccine adsorbed (AVA), in that the sole component is a recombinant form of protective antigen (PA). Unlike AVA the rPA vaccine contains no lethal factor (LF) or edema factor (EF), components of the two bipartite toxins, nor many other Bacillus anthracis-related contaminating proteins that are present in AVA. The proposed clinical protocol involves adsorption of the rPA to an aluminum-based adjuvant. The adsorptive characteristics of rPA and two aluminum-containing adjuvants were examined in a physiological buffer with and without EDTA. Based on the pI of rPA (pI=5.6) and the zero charge point of aluminum hydroxide adjuvant (11.5) and aluminum phosphate adjuvant (4.5), it was predicted and demonstrated that rPA bound in a more efficient manner to aluminum hydroxide adjuvant than to aluminum phosphate adjuvant in the physiological buffer. Binding of the rPA to the aluminum hydroxide adjuvant was decreased by increasing amounts of phosphate in the buffer. The adsorptive capacity for rPA onto aluminum hydroxide adjuvant in the physiological buffer and in water were calculated to be 0.46 mg rPA/mg aluminum in DPBS and 0.73 mg rPA/mg aluminum in water. This study also demonstrated that upon desorption from the aluminum hydroxide adjuvant the rPA was physically intact and free of detectable aggregates. Further, the eluted material was biologically active in an in vitro cytotoxicity assay. Desorption was only possible after an overnight incubation of 2-8 degrees C and not after a room temperature incubation reflecting increased contact with the aluminum hydroxide adjuvant over time. These data suggest that the interaction between rPA and aluminum hydroxide adjuvant is predominantly electrostatic in character.     

Oral immunization of adult volunteers with microencapsulated enterotoxigenic Escherichia coli (ETEC) CS6 antigen

As a step in the development of an oral vaccine against ETEC, we evaluated the safety and immunogenicity of CS6, a polymeric protein commonly found on the surface of ETEC. Formulations included 1 and 5mg doses of CS6, either encapsulated in biodegradable polymer poly(D, L)-lactide-co-glycolide (PLG), or as free protein, administered orally in a solution of either normal saline or a rice-based buffer. Three doses of CS6 were given at 2-week intervals. Blood was collected immediately before and 7 days after each dose. All formulations were well tolerated. Four of five volunteers who received 1mg CS6 in PLG microspheres with buffer had significant IgA ASC responses (median=30 ASC per 10(6) PBMC) and significant serum IgG responses (median=3.5-fold increase). Oral administration of these prototype ETEC vaccine formulations are safe and can elicit immune responses. The ASC, serum IgA, and serum IgG responses to CS6 are similar in magnitude to the responses after challenge with wild-type ETEC [Coster et al., unpublished data]. Further studies are underway to determine whether these immune responses are sufficient for protection.     

CD40 signaling is impaired in L. major-infected macrophages and is rescued by a p38MAPK activator establishing a host-protective memory T cell response

Leishmania, a protozoan parasite, lives and multiplies as amastigote within macrophages. It is proposed that the macrophage expressed CD40 interacts with CD40 ligand on T cells to induce IFN-gamma, a Th1-type cytokine that restricts the amastigote growth. Here, we demonstrate that CD40 cross-linking early after infection resulted in inducible nitric oxide synthetase type-2 (iNOS2) induction and iNOS2-dependent amastigote elimination. Although CD40 expression remained unaltered on L. major-infected macrophages, delay in the treatment of macrophages or of mice with anti-CD40 antibody resulted in significant reduction in iNOS2 expression and leishmanicidal function suggesting impaired CD40 signaling in Leishmania infection. The inhibition of CD40-induced iNOS2 expression by SB203580, a p38-mitogen activated protein kinase (p38MAPK)-specific inhibitor, and the reversal of the inhibition by anisomycin, a p38MAPK activator, suggested a crucial role of p38MAPK in CD40 signaling. Indeed, the CD40-induced p38MAPK phosphorylation, iNOS2 expression and anti-leishmanial function were impaired in Leishmania-infected macrophages but were restored by anisomycin. Anisomycin's effects were reversed by SB203580 emphasizing the role of p38MAPK in CD40-induced iNOS2-dependent leishmanicidal function. Anisomycin administration in L. major-infected BALB/c mice resulted in significant reduction in the parasite load and established a host-protective Th1-type memory response. Also implicated in these findings is a scientific rationale to define novel anti-parasite drug targets and to bypass the problem of drug resistance.     

Neural prosthetic control signals from plan activity

The prospect of assisting disabled patients by translating neural activity from the brain into control signals for prosthetic devices, has flourished in recent years. Current systems rely on neural activity present during natural arm movements. We propose here that neural activity present before or even without natural arm movements can provide an important, and potentially advantageous, source of control signals. To demonstrate how control signals can be derived from such plan activity we performed a computational study with neural activity previously recorded from the posterior parietal cortex of rhesus monkeys planning arm movements. We employed maximum likelihood decoders to estimate movement direction and to drive finite state machines governing when to move. Performance exceeded 90% with as few as 40 neurons.