Visual recognition based on temporal cortex cells: viewer-centred processing of pattern configuration

A model of recognition is described based on cell properties in the ventral cortical stream of visual processing in the primate brain. At a critical intermediate stage in this system, 'Elaborate' feature sensitive cells respond selectively to visual features in a way that depends on size (+/- 1 octave), orientation (+/- 45 degrees) but does not depend on position within central vision (+/- 5 degrees). These features are simple conjunctions of 2-D elements (e.g. a horizontal dark area above a dark smoothly convex area). They can arise either as elements of an object's surface pattern or as a 3-D component bounded by an object's external contour. By requiring a combination of several such features without regard to their position within the central region of the visual image, 'Pattern' sensitive cells at higher levels can exhibit selectivity for complex configurations that typify objects seen under particular viewing conditions. Given that input features to such Pattern sensitive cells are specified in approximate size and orientation, initial cellular 'representations' of the visual appearance of object type (or object example) are also selective for orientation and size. At this level, sensitivity to object view (+/- 60 degrees) arises because visual features disappear as objects are rotated in perspective. Processing is thus viewer-centred and the neurones only respond to objects seen from particular viewing conditions or 'object instances'. Combined sensitivity to multiple features (conjunctions of elements) independent of their position, establishes selectivity for the configurations of object parts (from one view) because rearranged configurations of the same parts yield images lacking some of the 2-D visual features present in the normal configuration. Different neural populations appear to be selectively tuned to particular components of the same biological object (e.g. face, eyes, hands, legs), perhaps because the independent articulation of these components gives rise to correlated activity in different sets of input visual features. Generalisation over viewing conditions for a given object can be established by hierarchically pooling outputs of view-condition specific cells with pooling operations dependent on the continuity in experience across viewing conditions. Different object parts are seen together and different views are seen in succession when the observer walks around the object. The view specific coding that characterises the selectivity of cells in the temporal lobe can be seen as a natural consequence of selective experience of objects from particular vantage points. View specific coding for the face and body also has great utility in understanding complex social signals, a property that may not be feasible with object-centred processing.     

Selective role for beta-protein kinase C in signaling for O-2 generation but not degranulation or adherence in differentiated HL60 cells

A role for protein kinase C (PKC) isotypes is implicated in the activation of phagocytic cell functions. An antisense approach was used to selectively deplete beta-PKC, both betaI- and betaII-PKC, but not alpha-PKC, delta-PKC, or zeta-PKC in HL60 cells differentiated to a neutrophil-like phenotype (dHL60 cells). Depletion of beta-PKC in dHL60 cells elicited selective inhibition of O-2 generation triggered by fMet-Leu-Phe, immune complexes, or phorbol myristate acetate, an activator of PKC. In contrast, neither ligand-elicited beta-glucuronidase (azurophil granule) release nor adherence to fibronectin was inhibited by beta-PKC depletion. Ligand-induced phosphorylation of a subset of proteins was reduced in beta-PKC-depleted dHL60 cells. Phosphorylation of p47(phox) and translocation of p47(phox) to the membrane are essential for activation of the NADPH oxidase and generation of O-2. beta-PKC depletion had no effect on the level of p47(phox) in dHL60 cells but did significantly decrease ligand-induced phosphorylation of this protein. Furthermore, translocation of p47(phox) to the membrane in response to phorbol myristate acetate or fMet-Leu-Phe was reduced in beta-PKC-depleted cells. These results indicate that beta-PKC is essential for signaling for O-2 generation but not cell adherence or azurophil degranulation. Depletion of beta-PKC inhibited ligand-induced phosphorylation of p47(phox), translocation of p47(phox) to the membrane, and activation of O-2 generation.     

Speech perception performance in experienced cochlear-implant patients receiving the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant

Sixteen experienced cochlear implant patients with a wide range of speech-perception abilities received the SPEAK processing strategy in the Nucleus Spectra-22 cochlear implant. Speech perception was assessed in quiet and in noise with SPEAK and with the patients' previous strategies (for most, Multipeak) at the study onset, as well as after using SPEAK for 6 months. Comparisons were made within and across the two test sessions to elucidate possible learning effects. Patients were also asked to rate the strategies on seven speech recognition and sound quality scales. After 6 months' experience with SPEAK, patients showed significantly improved mean performance on a range of speech recognition measures in quiet and noise. When mean subjective ratings were compared over time there were no significant differences noted between strategies. However, many individuals rated the SPEAK strategy better for two or more of the seven subjective measures. Ratings for "appreciation of music" and "quality of my own voice" in particular were generally higher for SPEAK. Improvements were realized by patients with a wide range of speech perception abilities, including those with little or no open-set speech recognition.     

Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.     

Perioperative specific management of blood volume loss in craniosynostosis surgery

Accurate assessment and replacement of blood loss and fluid-electrolyte deficit during craniosynostosis repair is difficult owing to patient size and the diversity of surgical technique. Forty-three patients undergoing primary craniosynostosis repair over a 10-year period were studied retrospectively to determine blood loss and fluid deficit and to assess blood transfusion practices during both intraoperative and postoperative periods. Blood loss was calculated on the basis of estimated red cell mass (ERCM) and fluid-electrolyte imbalance was investigated with blood samplings. Blood transfusion was considered appropriate if the postoperative or posttransfusion ERCM was within 12% of the preoperative value. Estimated fluid requirement (EFR) was used in 4 ml kg(-1) h(-1) except for neonates. Intraoperatively, 80% of all patients were appropriately managed with respect to blood transfusion and EFR. Postoperatively only 20% of the patients receiving transfusions were transfused appropriately. In 23.3% of these patients (10/43) unexpected respiratory distress developed immediately after their recovery from the anesthesia. With the measurement of estimated blood volume and allowable blood loss, appropriate transfusion could be achieved for the successful treatment of the primary craniosynostosis.     

Ethical and practical issues involved in behavioral pharmacology research that administers drugs of abuse to human volunteers

Researchers carrying out non-therapeutic research that involves the administration of drugs of abuse to human volunteers can be faced with many ethical and practical questions. The history of this type of research is relatively brief, with little in the way of published information relevant to carrying out behavioral pharmacological research with human participants. The aim of this article is to raise issues that occur in most studies of this type and to provide solutions that we have found acceptable and which have been approved by a variety of institutions and regulatory agencies. Clearly, there are other approaches that would work equally as well, and we are not attempting to provide 'the' answer to many of the issues raised. We believe that raising these issues and providing our perspectives is important for stimulating others to discuss them and for all of us to strive, where possible, to reach a consensus concerning ethical practices and to become aware of gaps and pitfalls. The topics discussed range from the nuts and bolts of acquiring and keeping track of drugs, to selecting research participants and designing ethical studies that protect our volunteers while still collecting scientifically useful data.     

CD8+CD103+ T cells analogous to intestinal intraepithelial lymphocytes infiltrate the pancreas in chronic pancreatitis

OBJECTIVE: Chronic pancreatitis is a painful chronic inflammatory disease of the exocrine pancreas that is associated with the replacement of functional parenchyma by extended fibrosis and with a massive infiltration of T lymphocytes. However, to date further characterization of infiltrating T cells in chronic pancreatitis has not been undertaken. METHODS: Using the novel method of multiepitope imaging with fluorochrome-tagged specific monoclonal antibodies, which allows the simultaneous localization and characterization of T cells in tissues, we analyzed the distribution and phenotypes of T cells infiltrating the pancreas in chronic pancreatitis. RESULTS: The mean CD4:CD8 ratio in 10 cases of chronic pancreatitis was 2.4:1. In order of decreasing frequency, the following markers were observed: CD45RO, CD18, TCRgammadelta, and CD103. The lymphocytes, especially of the CD4+ subset, were found mainly in the fibrous stroma, but T cells were also observed periductally. A T-cell subset bearing the phenotype CD8+CD103+, analogous to intestinal intraepithelial lymphocytes, was found intracalating between the cells of the ductal epithelium. CONCLUSIONS: Phenotyping of the T lymphocytes in chronic pancreatitis supports the concept of the involvement of cell-mediated cytotoxicity in the pathogenesis of this disease. In addition, intraepithelial lymphocytes were found interspersed between the ductal epithelial cells, pointing to a role of this T-cell subset as a first-line defense against deleterious epithelial events in chronic pancreatitis.     

Dilutional and modified ultrafiltration reduces pulmonary hypertension after operations for congenital heart disease: a prospective randomized study

OBJECTIVE: A prospective randomized study was performed to test whether removal of endothelin-1, by ultrafiltration techniques, will reduce pulmonary hypertension after operations for congenital heart disease. METHODS: Twenty-four patients with pulmonary hypertension (systolic pulmonary/systemic arterial pressure ratio > 60%) undergoing cardiac operations were randomized into a control group (n = 12) having conventional ultrafiltration and an experimental group (n = 12) undergoing dilutional ultrafiltration during and modified ultrafiltration after cardiopulmonary bypass. Plasma endothelin-1, nitric oxide metabolites, and cyclic guanosine monophosphate were assayed before bypass, 10 minutes into bypass, after bypass, and 0, 3, 6, and 12 hours after the operation in both groups, as well as in the ultrafiltrates and after modified ultrafiltration in the experimental group. Both groups received alpha-blockers (chlorpromazine and/or prazosin) postoperatively using the same guidelines. RESULTS: The ultrafiltrates contained significant amounts of endothelin-1 (1.81 +/- 0.86 pg/ml, dilutional, and 6.44 +/- 1.82 pg/ml, modified ultrafiltrate). Endothelin-1 and the pulmonary/systemic pressure ratio were significantly lower in experimental compared with control patients. Nitric oxide metabolites and cyclic guanosine monophosphate increased similarly in both groups for 12 hours after the operation (p = not significant). Three of 12 control patients (25%) but no experimental patients had pulmonary hypertensive crises (p = 0.07). The experimental patients required significantly less ventilatory support (67 +/- 47 hours vs 178 +/- 139 hours for control patients, p = 0.048). CONCLUSIONS: Dilutional and modified ultrafiltration reduce endothelin-1 and the pulmonary/systemic pressure ratio postoperatively and may become an important adjunct for preventing pulmonary hypertension after operations for congenital heart disease in high-risk patients.     

Long term effects of 50 mg acetylsalicylic acid alone and in combination with dipyridamole on platelet function after coronary bypass surgery

In a prospective randomized trial in 42 patients undergoing coronary artery bypass surgery, we analyzed the long term platelet inhibiting effects of 50 mg acetylsalicylic acid (ASA) by itself and in combination with dipyridamole (2 x 200 mg), in comparison with phenprocoumon. Three and six months therapy led to significant inhibition of maximum aggregation induced by collagen 1 microgram/ml in platelet rich plasma (PRP) by more than 50% (p < or = 0.05). In PRP stimulated with 5 micrograms/ml collagen maximum inhibition amounted to nearly 20% (n.s.). The groups treated with ASA/ASA + dipyridamole showed an ADP threshold concentration 2.5 times higher than the group treated with phenprocoumon (p < or = 0.05). After stimulation with collagen 1 microgram/ml and 5 micrograms/ml thromboxane B2 synthesis in vitro in both groups treated with ASA was reduced to 1% of the base line values (p < or = 0.01). Inhibition of aggregation in whole blood appeared evident, but was not statistically significant due to considerable fluctuation of measurement. An additional effect of dipyridamole was not detectable. In conclusion, treatment with 50 mg ADA/d results in a lasting, effective inhibition of aggregation of platelets in patients with coronary artery bypass surgery. There is no synergistic effect of additional dose of 400 mg dipyridamole/d.