Regulation of mast cell signaling through high-affinity IgE receptor by CD45 protein tyrosine phosphatase

The transmembrane tyrosine phosphatase CD45 regulates the activity of src family protein tyrosine kinases (PTK) and thereby influences the signaling via such receptors as T and B cell antigen receptors associated with these PTK. However, its implication in signaling through the mast cell receptor with high affinity for IgE (FcepsilonRI) is less clear, although Lyn, a member of the src family, plays an important role in FcepsilonRI-mediated signaling. To define a role for CD45 in FcepsilonRI signal transduction, we established CD45 high expressing rat basophilic leukemia cell lines (RBL-CD45H) and cell lines expressing trace amounts of CD45 (RBL-CD45L). We demonstrate that although all RBL-CD45L cell lines degranulate following IgE- and antigen-induced FcepsilonRI aggregation, the response is significantly reduced at a low dose of antigen. The cells show a delayed and slowed Ca(2+) mobilization even though at a higher dose where the cells degranulate to a similar extent as RBL-CD45H. This diminished Ca(2+) response is restored by reconstitution of RBL-CD45L with a chimeric molecule containing the cytoplasmic phosphatase domains of rat CD45. Furthermore, tyrosine phosphorylation of FcepsilonRI, association of FcepsilonRI with Lyn and PTK activity associated with FcepsilonRI, all of which are enhanced upon FcepsilonRI aggregation in RBL-CD45H, are impaired in RBL-CD45L. Finally, we show that FcepsilonRI is physically associated with CD45 in RBL-CD45H prior to receptor aggregation. Thus, we propose that, although not indispensable in mast cell degranulation, CD45 positively regulates the signaling through FcepsilonRI by promoting the activation of FcepsilonRI-associated Lyn.     

No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients

Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc.     

Lung cancer metastasis to adrenocortical adenomas. A chance occurrence or a predilected phenomenon?

To evaluate the common belief that cancer metastasis to adrenocortical adenomas is a predilected phenomenon, we compared the real incidence of cancer metastasis obtained by analyzing the autopsy results of our 160 lung cancer cases, as well as those found by reviewing the literature, with the theoretical incidence obtained through the simulation models we made. The results disclosed that statistically, the real incidence was significantly higher than the theoretical probability. Therefore, we concluded that the metastasis of lung carcinoma to adrenocortical adenomas is indeed predilected.     

Follicle structure-dependency of thyroglobulin and thyroxin staining in the thyroid glands of Graves' disease

H.E. morphology of the thyroid glands from 170 patients with Graves' disease was studied, and the thyroid follicles were classified into two main groups: (1) F pattern, in which the follicles show circle/ellipse on cut sections; (2) P pattern, in which the follicular epithelium protrudes into the lumen or a follicle, is accompanied by proliferation of tubular or microfollicular structures. Studies on three serial sections of 88 thyroid glands stained with hematoxylin and eosin, thyroglobulin (TG), and thyroxin (T4), respectively, revealed the followings: (i) TG/T4 staining is dependent on the follicle structure (i.e., F or P); while the epithelium and colloid including scalloped vesicles in F follicles generally exhibited a direct relationship between TG and T4 staining, those in P follicles often showed an intense TG, but negative T4 staining. (ii) The results of morphological and immunohistochemical studies of P follicles among the cases are consistent with the view that P follicles are in the process of proliferation of immature daughter follicles from a main follicle and of their maturation. (iii) P follicles of Graves' thyroid glands were evaluated as possible non-neoplastic counterparts of well-differentiated follicular and papillary tumors.     

Further insight into the task-dependent excitability of motor evoked potentials in first dorsal interosseous muscle in humans

We have reexamined the contradictory evidence in which task-dependent excitation of motor evoked potentials (MEPs) in the first dorsal interosseous (FDI) muscle was stronger with increasingly more complex finger tasks than with individual finger movement tasks. In the first step of the experiment, based on previous findings, we investigated remarkable functional differences between intrinsic and extrinsic hand muscles during complex finger tasks (precision and power grip). During the performance of the tasks, the optimal stimulus intensity of the transcranial magnetic stimulation (TMS) was applied to the contralateral motor cortex. MEPs of the FDI, extensor carpi radialis (ECR), and flexor carpi radialis (FCR) muscles were recorded simultaneously with increased background EMG activity step by step in both tasks. The intensity threshold of TMS was lower in the precision grip. Furthermore, the MEP amplitudes of FDI muscle dependent on the background EMG activity were different between these two tasks, i.e., MEP amplitudes and regression coefficients in a precision grip were larger than those in a power grip. Although our results for MEP amplitude and threshold in the FDI muscle were similar to previous reported evidence, the different contributions of a synergistic muscle (in particular, the ECR muscle) during performance in these tasks was new evidence. Since there were no differences in cutaneous afferent effects on both tasks, corticomotoneuronal (CM) cells connected to FDI motoneurons seemed generally to be more active during precision than power gripping, and there were different contributions from synergistic muscles during the performance of these tasks. In the second part of the experiment, the results obtained from the complex tasks were compared with those from a simple task (isolated index finger flexion). MEP amplitudes, dependent on the background EMG activity during isolated index finger flexion, varied among subjects, i.e., the relationship between the MEP amplitude and the background EMG of the FDI muscle showed individual, strategy-dependent modulation. There were several kinds of individual motor strategies for performing the isolated finger movement. The present results may explain the previous contradictory evidence related to the contribution of the CM system during coordinated finger movement.     

Three-dimensional distribution patterns of PRL,GH and ACTH cells in the house musk shrew ( Suncus murinus)

Despite a multitude of reports on the classification and distribution of anterior pituitary cells, no previous study has attempted to obtain the three-dimensional (3D) and computer-graphic distribution pattern of each cell type in the whole pituitary. Therefore, we mapped the anterior pituitary cells of the house musk shrew ( Suncus murinus) and found a distinct cellular distribution pattern. Serial horizontal sections of whole shrew pituitaries were stained immunohistochemically for prolactin (PRL), growth hormone (GH), and adrenocorticotropic hormone (ACTH) cells. The contours of positive cells and the anterior, intermediate, and posterior lobes in each section were digitized for 3D visualization by a volume rendering method. The reconstructed images and virtual frontal and sagittal slices were examined in detail. On the 3D reconstructed images, the PRL and GH cells had similar distribution patterns, although the former were concentrated in the dorsolateral and ventrocentral portions, and the latter in the dorsocentral portions of the anterior lobe. On both sides of the pituitary stalk, there lay portions that were conspicuous by scarcity of PRL and GH cells. ACTH cells were widely scattered throughout the whole anterior lobe, but they were very few in the above portions and the dorsocentral portions where GH cells were concentrated. No sex difference in the distribution patterns of each cell type was observed. However, PRL cells in females were more numerous than in males, whereas the opposite was true for GH and ACTH cells. We discuss the relationship between the formation of the spatial distribution patterns and anterior pituitary ontogeny.