The orchestration of the sensory-motor systems: Clues from Neuropsychology

Research over the last several decades has led to clear and empirically tractable proposals about the representation of conceptual knowledge in the brain. Here we argue that there are already sufficient data from neuropsychology to strongly constrain extant hypotheses about the representation of conceptual knowledge. One constraint imposed by these neuropsychological data is that recognition of actions and understanding of objects do not necessarily depend on the ability to produce object-associated actions. This conclusion compels a reconsideration of the role played by motor planning and/or execution processes in action and object recognition and understanding.     

Optical anisotropy of a pig tendon under compression*

The proximal region of the superficial digital flexor tendon of pigs passes under the tibiotarsal joint, where it is subjected to compressional and tensional forces. This region was divided into a surface portion (sp), which is in direct contact with the bone and into a deep portion (dp), which is the layer opposite the articulating surface. The purpose of this work was to analyse the distribution and organisation of the collagen bundles and proteoglycans in the extracellular matrix in sp and dp. Toluidine‐blue‐stained sections were analysed under a polarising microscope. Strong basophilia and metachromasia were observed in sp, demonstrating accumulation of proteoglycan in a region bearing compression, but the intensity was reduced the further layers were from the bone. Linear dichroism confirmed that the glycosaminoglycan molecules were disposed predominantly parallel to the longest axis of the collagen fibrils. Birefringence analysis showed a higher molecular order and aggregation of the collagen bundles in areas where the tension was more prominent. The crimp pattern was more regular in dp than in sp, probably as a requirement for tendon stretching. The optical anisotropy exhibited by the collagen bundles also confirmed the helical organisation of the collagen bundles in the tendon. Hyaluronidase digestion caused a decrease in the basophilia, but this was not eliminated, supporting the idea that in the matrix, proteoglycans are not completely available to the enzyme action.     

Postoperative spindle cell nodule of the breast: Pseudosarcomatous myofibroblastic proliferation following endo‐surgery

Despite the frequent use of fine‐needle aspiration, core biopsy and surgery, postoperative spindle cell nodule (PSCN) is a rare pathological complication that may be diagnostically treacherous. Presented herein is the case of a 52‐year‐old woman who developed a 7 mm mammary nodular lesion 66 days after removal of an area of columnar cell hyperplasia involving cellular and architectural atypia, performed with the Mammotome Breast Biopsy System. The lesion was highly cellular and composed of intersecting fascicles of plump spindle cells with blunt‐ended elongated nuclei and nucleoli easily visible. Interspersed mononuclear cells and hemosiderin‐laden macrophages were evident. PSCN is a reactive, benign myofibroblastic proliferation. Differential diagnosis includes benign and malignant spindle cell lesions of the breast. Recognition of this reactive lesion will avoid overdiagnosis of spindle cell malignant tumor. Attention to clinicopathological and histological features should result in accurate recognition of this lesion.     

Orbital meningioma with a granular cell component in a dog, with extracranial metastasis

A meningioma with a significant component of granular cells is described in the left ocular orbit of a 5-year-old male Golden retriever dog that presented with exophthalmos. The neoplastic mass surrounded the optic nerve. Microscopically, the tumour was characterized by nests of large, round to polygonal cells, variable in size, with eccentric nuclei and abundant eosinophilic cytoplasm, containing PAS-positive granules. In focal areas, cells were smaller and occasionally formed whorl-like structures. Immunohistochemical analysis revealed that neoplastic cells reacted positively for vimentin and, with less intensity, for neuron specific enolase and S-100, whereas they were negative for glial fibrillary acidic protein and cytokeratins. Metastatic growths, formed by similar cells, were seen in the lung and heart.     

Induced recruitment of NK cells to lymph nodes provides IFN-gamma for T(H)1 priming

Naive T cells are stimulated by antigen-presenting dendritic cells (DCs) in secondary lymphoid organs, but whether other types of cell participate in T cell priming is unclear. Here we show in mice that natural killer (NK) cells, which are normally excluded from lymph nodes, are rapidly recruited in a CCR7-independent, CXCR3-dependent manner to lymph nodes on stimulation by the injection of mature DCs. Recruitment of NK cells is also induced by some, but not all, adjuvants and correlates with the induction of T helper cell type 1 (T(H)1) responses. NK cell depletion and reconstitution experiments show that NK cells provide an early source of interferon-gamma (IFN-gamma) that is necessary for T(H)1 polarization. Taken together, our results identify an induced pathway of NK cell migration in antigen-stimulated lymph nodes and a mechanism by which some adjuvants may facilitate T(H)1 responses.     

Migration of human blood dendritic cells across endothelial cell monolayers: adhesion molecules and chemokines involved in subset-specific transmigration

Distinct subsets of dendritic cells (DCs) are present in blood, probably "en route" to different tissues. We have investigated the chemokines and adhesion molecules involved in the migration of myeloid (CD11c(+)) and plasmacytoid (CD123(+)) human peripheral blood DCs across vascular endothelium. Among blood DCs, the CD11c(+) subset vigorously migrated across endothelium in the absence of any chemotactic stimuli, whereas spontaneous migration of CD123(+) DCs was limited. In bare cell migration assays, myeloid DCs responded with great potency to several inflammatory and homeostatic chemokines, whereas plasmacytoid DCs responded poorly to all chemokines tested. In contrast, the presence of endothelium greatly favored transmigration of plasmacytoid DCs in response to CXCL12 (stromal cell-derived factor-1) and CCL5 (regulated on activation, normal T expressed and secreted). Myeloid DCs exhibited a very potent transendothelial migration in response to CXCL12, CCL5, and CCL2 (monocyte chemoattractant protein-1). Furthermore, we explored whether blood DCs acutely switch their pattern of migration to the lymph node-derived chemokine CCL21 (secondary lymphoid-tissue chemokine) in response to microbial stimuli [viral double-stranded (ds)RNA or bacterial CpG-DNA]. A synthetic dsRNA rapidly enhanced the response of CD11c(+) DCs to CCL21, whereas a longer stimulation with CpG-DNA was needed to trigger CD123(+) DCs responsive to CCL21. Use of blocking monoclonal antibodies to adhesion molecules revealed that both DC subsets used platelet endothelial cell adhesion molecule-1 to move across activated endothelium. CD123(+) DCs required beta(2) and beta(1) integrins to transmigrate, whereas CD11c(+) DCs may use integrin-independent mechanisms to migrate across activated endothelium.     

Complete Primary Sequences of Two λ Immunoglobulin Light Chains in Myelomas with Nonamyloid (Randall-Type) Light Chain Deposition Disease

We herein report on the first two primary sequences (BOU and RAC) of monoclonal light chains of the λ type responsible for nonamyloid λ light chain deposition disease. Both patients were affected with severe forms of myeloma complicated with renal failure. The pathological presentation typically featured Congo red-negative deposits along tubular basement membranes but differed somewhat from the typical “Randall-type” κ light chain deposition disease: they lacked the prominent glomerulosclerosis pattern often featuring nonamyloid κ deposits and were associated with cylinders or myeloma casts. Both protein sequences were deduced from those of the corresponding complementary DNAs in the bone marrow plasma cells. For each chain, products of three independent amplifications by polymerase chain reaction were sequenced and found to be identical. BOU and RAC λ mRNAs had a normal overall structure consisting of Vλ2 segments rearranged to Jλ2Cλ2 but displayed a number of unusual features within their primary sequences. These substitutions are likely responsible for changes in light chain conformation that promote their aggregation and deposition along renal tubule basement membranes.