An electron microscopic study of neurosecretion in the cerebral ganglion of the earthworm

Non-synaptic, exocytotic release of neurosecretory granules in cerebral ganglion neurons was observed electron microscopically in 3 species of the oligochaete annelids Aporrectodea caliginosa, Octolasion cyaneum and Lumbricus terrestris. In addition to the features indicating exocytotic release of neurosecretory granules into perineuronal space, possible features of neurosecretion into blood vessels were seen within the cerebral ganglion. Axon terminals in synaptic contact with perikaryal profiles of cerebral ganglion neurons were also found.     

Time-resolved particle image velocimetry and laser doppler anemometry study of the turbulent flow field of bileaflet mechanical mitral prostheses

Dynamic particle image velocimetry (PIV) was applied to the study of the flow field associated with prosthetic heart valves. The results were compared with those of laser Doppler anemometry (LDA). Anatomically and antianatomically oriented Jyros (JR) and St. Jude Medical (SJM) valves were compared in the mitral position to study the effects of valve design on the downstream flow field. The experimental program used a dynamic PIV system utilizing high-speed, high-resolution video to map the true time-resolved velocity field inside the simulated ventricle. This system was complemented by a study using the more traditional LDA system for comparison. Based on the experimental data, the following general conclusions can be made. High-resolution dynamic PIV can capture true chronological changes in the velocity and turbulence fields. It also produces very detailed velocity and turbulence information comparable to the LDA results. In the vertical measuring plane that passes both the center of the aortic and mitral valves (A-A section), the two valves (the SJM and the JR) show distinct circulatory flow patterns when the valve is installed in the antianatomical orientation. Small differences in valve design can generate noticeable differences, particularly during the accelerating flow phase. The SJM valve maintains a relatively high velocity through the central orifice; the curved leaflets of the JR valve generate higher velocities with a divergent flow during the accelerating and peak flow phases. In the velocity field directly below the mitral valve and normal to the previous measuring plane (B-B section), where characteristic differences in valve design will be visible, symmetrical twin circulations were observed because of the divergent nature of the flow generated by the two inclined half-disks installed in the antianatomical orientation. The SJM valve, with a central downward flow near the valve, is contrasted with the JR valve, which has a peripheral downward circulation with higher, turbulent stresses.     

Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.     

ABC proteins: key molecules for lipid homeostasis

Forty-nine ABC protein genes exist on human chromosomes. Eukaryotic ABC proteins were originally recognized as drug efflux pumps involved in the multidrug resistance of cancer cells. However, it is now realized that one of their major physiological roles is cellular lipid transport and homeostasis, and their dysfunction is often associated with human diseases. ABCA1 and ABCA7 mediate the apolipoprotein-dependent formation of a high-density lipoprotein–cholesterol complex. ABCA3 is indispensable for pulmonary surfactant secretion. ABCG5 and ABCG8 are involved in the secretion of plant sterols and cholesterol into bile. However, the primary substrates and mechanism of action of these ABC proteins have not been precisely defined. In this review article, we first describe the general structure and functions of eukaryotic ABC proteins. The current model of ABCA1 functionality is then explained based on studies on a topological model, subcellular localization, apoA-I dependence of HDL formation, functional defects of Tangier disease mutants, and ATP hydrolysis of purified ABCA1. ABCA1 is supposed to function as a transporter of lipids as well as a receptor for apoA-I. ABCA3 is likely involved in accumulating phospholipids and cholesterol in lamellar bodies and in generating multivesicular structures.     

Interaction between the immune and central nervous systems

Much of the understanding of tolerance has focused on the requirements for antigen-specific lymphocyte activation and function. However, there is increasing evidence for anatomic regulation of effector access to self antigens. Recently, a number of studies have provided evidence for tissue-specific “addressins” in chemokine/chemokine receptor pairs. The central nervous system (CNS) provides special anatomic barriers to the movement of cells from the vascular compartment to the parenchyma. Herein I raise the possibility that antigen, perhaps through specialized antigen-presenting cells, may play a role in regulating access of activated lymphocytes into the CNS parenchyma. The results suggest that a reexamination of the widely held dogma that all activated lymphocytes have access to the CNS parenchyma is nessary to understand the relationship between the immune and central nervous systems.     

Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.     

The role of climbing fibers in the development of Purkinje cell dendrites

Destruction of the inferior olivary nucleus was performed in newborn kittens in order to study the role of climbing fibers in the postnatal development of the cerebellum. In the three kittens which survived for 40–45 days after the unilateral destruction at 2 days old, histological examination demonstrated the lack of dendritic arborization in many Purkinje cells in the cerebellar cortex contralateral to the lesion. The olivectomized kittens showed cerebellar symptoms which became conspicous when the kittens started to walk. The results reveal an important role of climbing fibers in the development of Purkinje cell dendrites.     

The effect of immunotherapy on eosinophil accumulation and production of eosinophil chemotactic activity in the lung of subjects with asthma during natural pollen exposure

Two groups of birch pollen--allergic patients with seasonal rhinoconjunctivitis and asthma were followed during two consecutive birch-pollen seasons, one group, N = 10, during a season with high pollen load, and one group, N = 15, during a season of low pollen load. Half the patients were treated with immunotherapy (IT) for 3 and 4 years, respectively. The other half of the patients served as control group (non-IT). Bronchoalveolar lavage (BAL) was performed once before each season and once during the pollen season. Eosinophil (EOS) numbers in BAL were increased (p less than 0.01) during the season with high pollen load but not in the season with a low pollen load, and this increment was absent in the IT-treated group. Also, the EOS cationic protein levels were raised in the non-IT-treated group during the season with a high pollen load. The levels of EOS and neutrophil chemotactic activity were raised in BAL in both seasons in the non-IT-treated group compared with the IT-treated group (p less than 0.02, p less than 0.003, p less than 0.04, and p less than 0.005 in high- and low-load pollen season, respectively). Serum and BAL eosinophil chemotactic activity (ECA) were positively correlated (p less than 0.001). We conclude that there is an influx of active EOSs into the lung of pollen-allergic patients with asthma during a pollen season, which may be abrogated by IT. Furthermore, the generation of ECA appears to be an extremely sensitive marker of antigenic exposure, and the potent inhibition of the generation of ECA by IT may provide a clue as to the mechanism of this treatment.     

Topographical projections from the thalamus to the putamen in the cat

Thalamic projections to the putamen (Put) in the cat were studied by the retrograde horseradish peroxidase method. Major thalamic projections to the Put originate from the midline and intralaminar nuclear regions including the centre médian-parafascicular complex (CM-Pf). The other thalamic projections to the Put arise mainly from the suprageniculate nucleus (Sg), magnocellular division of the medial geniculate nucleus (MGm), caudomedial part of the lateroposterior nucleus (LP) and ventrolateral part of the ventromedial nucleus (VM). The VM projects to the rostral Put, while the posterior thalamic regions (Sg, MGm, LP) project to the caudal Put.