We examined the expression and localization of the prohormone convertases, PC1 and PC2, in the anterior pituitary cells of developing rats by a double staining procedure using in situ RT-PCR and an immunofluorescence technique. In the adult, both PC1 mRNA and PC2 mRNA were expressed in corticotrophs, gonadotrophs, thyrotrophs, and mammotrophs. These cells, except for corticotrophs, had previously been considered to be ones in which proprotein processing does not take place, but both PC1 and PC2 may be necessary to process other proteins, such as granin family proteins, having proteolytic cleavage sites and located in secretory granules of the above trophs. In addition, no PC1 or PC2 mRNA was expressed in somatotrophs, which is consistent with the fact that somatotrophs do not contain these granins. In addition, 7B2 mRNA was expressed in these PC2-positive trophs, suggesting that there is a functional relationship between PC2 and 7B2 proteins. We found that alpha-MSH was expressed in the corticotrophs of the postnatal rat and that the number of alpha-MSH-immunopositive corticotrophs decreased as development proceeded. Because the changes in the pattern of POMC processing are considered to depend on the relative expression levels of PC1 and PC2, PC1 and PC2 mRNAs were examined in corticotrophs during postnatal development. We found a decrease in the number of PC2 mRNA-positive cells, which coincided with one in the number of alpha-MSH-immunopositive corticotrophs, as postnatal development proceeded. Our present data demonstrate that the alpha-MSH production varies directly in accordance with the expression of PC2. We also discuss the possible significance of alpha-MSH production during the postnatal period.

Metastasis is the chief cause of mortality in cancer patients. Recently, chemokines and chemokine receptors were shown to play an important role in the metastasis of various cancers. We examined the role of chemokine receptor‐mediated signaling in the invasion potential of human oral squamous cell carcinoma (OSCC) cell lines that were derived from 5 primary tumors and 6 cervical lymph node metastases. Comprehensive analysis of the mRNAs for human chemokine receptors showed that the OSCC cell lines had uniform expression patterns of chemokine receptors. Overall, there were no consistent differences in the expression of chemokine receptors between primary site‐ and lymph node metastasis‐derived cell lines. However, a highly invasive OSCC cell line (SAS‐Hl) expressed up‐regulation of CCR5, CCR6, CCR7, CXCR1, CXCR6 and CX3CR1 compared to a poorly invasive OSCC cell line (SAS‐Ll). Then we examined whether factors in the tumor microenvironment regulated chemokine receptor expression in SAS‐Hl cells. Specifically, transforming growth factor (TGF) ‐β1 enhanced the expression of CCR5, CCR6, CCR7 and CX3CR1. Pretreatment of SAS‐Hl cells with transforming growth factor (TGF) ‐β1 increased the expression of CCR7 and CX3CR1, and then enhanced CCL21‐ and CX3CLl‐induced directional migration (l.5‐fold enhancement as compared with untreated control). In addition, CX3CL1 increased the adhesion of SAS‐Hl cells on uncoated tissue culture plates. Neither chemokine stimulated cell proliferation. Treatment of SAS‐Hl cells with CX3CL1 activated the phosphotidylinositol‐3‐kinase (PI3K) and MEK signal transduction pathways. Our results suggest that chemokine receptor‐mediated signaling is involved in the local invasion and metastasis of human OSCC.

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A 23-year-old woman presented with disturbance of consciousness and seizure. Her blood pressure was remarkably high, and brain magnetic resonance imaging (MRI) showed high-intensity T2 signals in the bilateral basal ganglia, corpus callosum, cerebral white matter, and cortex. With the administration of angiotensin II receptor blocker, the symptoms and MRI findings improved, along with normalization of blood pressure, and a diagnosis of posterior reversible leukoencephalopathy syndrome (PRES) was made. Plasma renin activity was high, and the right kidney was severely atrophic. Results from renal and adrenal vein sampling revealed renal vascular hypertension derived from the right renal artery stenosis. The right kidney was then removed by laparoscopic nephrectomy. Pathological examination of the kidney confirmed the diagnosis of fibromuscular dysplasia (FMD). In juvenile-onset encephalitis/encephalopathy, PRES due to FMD should be included in the differential diagnosis.

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