Rachel Koshi

Abnormalities in neuromuscular junction structure and skeletal muscle function in mice lacking the P2X2 nucleotide receptor

ATP is co-released in significant quantities with acetylcholine from motor neurons at skeletal neuromuscular junctions (NMJ). However, the role of this neurotransmitter in muscle function remains unclear. The P2X2 ion channel receptor subunit is expressed during development of the skeletal NMJ, but not in adult muscle fibers, although it is re-expressed during muscle fiber regeneration. Using mice deficient for the P2X2 receptor subunit for ATP (P2X2(-/-)), we demonstrate a role for purinergic signaling in NMJ development. Whereas control NMJs were characterized by precise apposition of pre-synaptic motor nerve terminals and post-synaptic junctional folds rich in acetylcholine receptors (AChRs), NMJs in P2X2(-/-) mice were disorganized: misapposition of nerve terminals and post-synaptic AChR expression localization was common; the density of post-synaptic junctional folds was reduced; and there was increased end-plate fragmentation. These changes in NMJ structure were associated with muscle fiber atrophy. In addition there was an increase in the proportion of fast type muscle fibers. These findings demonstrate a role for P2X2 receptor-mediated signaling in NMJ formation and suggest that purinergic signaling may play an as yet largely unrecognized part in synapse formation.

A Monkey Model for Enterohemorrhagic Escherichia coli Infection

Adult Macaca radiata (n=22) were infected intragastrically with 10(12) Escherichia coli O157:H7 strain 84-01, which produces Shiga toxins 1 and 2. Clinical symptoms and bacterial excretion were documented in each monkey for a specified time period before they were killed. At necropsy, samples were obtained for culture and histologic and ultrastructural examination. Seventeen monkeys had diarrhea: E. coli O157 was isolated from postinfection stool samples from all monkeys and from autopsy cultures for 14 of 22 monkeys. Histologic examination showed attaching-effacing lesions, which appeared at 12 h and persisted for 7 days, in 12 monkeys. Widening of the intercellular spaces, degeneration and vacuolization of the epithelial cells, epithelial tufting, extrusion of epithelial cells, and neutrophilic infiltration were characteristic features seen in 20 of the 22 infected monkeys but not in 4 control monkeys. This monkey model closely parallels the early stages of the disease produced by E. coli O157:H7 and would be useful in the further study of pathogenic mechanisms and prevention methods in enterohemorrhagic E. coli infections.

Vimentin, cytokeratin 8 and cytokeratin 18 are not specific markers for M-cells in human palatine tonsils.

Standard immunohistochemical methods were used to detect the presence of vimentin, cytokeratin 8, cytokeratin 18, macrophages and Langerhans cells in the human tonsillar epithelium in formalin‐fixed and frozen tissue specimens. Vimentin detection was restricted to infiltrating cells of the lymphoid series, dendritic and vascular endothelial cells. All epithelial cells were negative. Cytokeratin 8 and 18 were readily detected in a large proportion of epithelial cells lining the crypt, but these cells bore no resemblance to the intestinal M‐cells. Langerhans cells and macrophages were seen in both the oropharyngeal and crypt epithelium and were more common in the latter. This study confirms the presence of antigen‐presenting cells, macrophages and Langerhans cells in the tonsillar epithelium and shows that intermediate filament proteins, vimentin, cytokeratin 8 and 18 are unreliable markers for human tonsillar M‐cells, if indeed such cells exist in human tonsils.

Morphology of the corpus callosum in human fetuses

Shape and size of the human fetal corpus callosum of a relatively racially homogeneous southern Indian sample population were studied in midsagittal sections of formalin fixed brains. Length of corpus callosum and width of its genu, body, and splenium were measured and the data statistically analyzed. Presence of an isthmus between the body and splenium did not correlate with the measured variables. There was no significant gender difference. The variables correlated significantly among each other but only callosal length and genu width correlated with gestation age. Significant absolute increase occurred in callosal length and genu width, whereas body and splenium widths remained the same. Simple regression equations to estimate the callosal length and genu width for a given age are derived. Clin. Anat. 10:22–26

Introduction to histology through the use of familiar objects: Innovative teaching module

To introduce first‐year medical students to fundamental concepts in histology and facilitate interpretation of two‐dimensional images in the context of the three‐dimensional nature of the object, a simple teaching module consisting of active exercises plus group discussions, using familiar objects from everyday use, was planned. In the process of mentally reconstructing sections through familiar objects, and representing in diagrams the appearance of these sections, students learned the use of common histology terms; the value of studying sections in series and at different planes; and spatial relationships of a) a nucleus within a cell, and b) tissue components within solid and hollow organs. Their understanding of these concepts was found to be good when evaluated by a multiple‐choice‐questions test, suggesting that this is an effective method for introducing beginners to fundamentals of histology. Clin. Anat. 10:333–336, 1997.

Problem in diagnostic imaging: pancreaticoduodenal arcade in splanchnic arterial stenosis.

This paper features a problem in diagnostic imaging in which a pre‐transplant abdominal angiogram of a potential liver recipient shows filling of the hepatic artery via the superior mesenteric artery and the pancreaticoduodenal arcade. The routing of this unusual supply to the liver is explained by careful study of abdominal aortic angiograms and a sagittal MRI made through the aorta. Clin. Anat. 11:206–208, 1998.