Fractalkine and inflammatory diseases]

The migration of leukocytes into inflamed peripheral tissues and lymphoid organs involves a cascade of molecular events finely regulated by cell adhesion molecules and chemokines. Fractalkine/CX3CL1 is a membrane-bound chemokine that functions not only as a chemoattractant but also as an adhesion molecule, and is expressed on endothelial cells activated by proinflammatory cytokines. The fractalkine receptor, CX3CR1, is expressed on cytotoxic effector lymphocytes including NK cells and cytotoxic effector T cells (T(CE)), mature monocytes/macrophages, and mucosal dendritic cells, all of which play important roles in elimination of pathogens and cancer cells. Recently, accumulating evidence in both clinical studies and animal disease models has shown that fractalkine is also involved in the pathogenesis of various chronic inflammatory diseases, such as rheumatoid arthritis and atherosclerosis. This article reviews the unique functions of fractalkine and its pathophysiological roles in various clinical conditions.     

Endoscopic and Histologic Findings of Intraductal Lesions Presenting with Nipple Discharge

Abstract:   To improve the utility of mammary ductoscopy, we investigated the correlation between endoscopic findings and histologic findings using intraductal biopsy specimens. Seventy-one intraductal biopsy specimens obtained from 63 patients between October 2001 and March 2004 were analyzed retrospectively. All specimens were obtained from monotonous intraductal lesions immediately after observation by mammary ductoscopy and were composed of a pure histologic subtype. With regard to endoscopic findings, color was classified as yellow, red, white, or colorless, and morphology was classified as spherical, lobular, mulberry, or amorphous. The histologic subtype was classified as papillotubular, papillary, degenerated, papillary cancer, solid-type ductal carcinoma in situ (DCIS), or cribriform cancer. The relationship between histologic diagnosis, color, and morphology was investigated. Intraductal biopsy specimens included 25 specimens of carcinoma and 46 specimens of papilloma. There was no significant correlation between color and diagnosis. Fourteen of 25 carcinoma specimens were amorphous, and amorphous morphology was significantly suggestive of malignancy (p < 0.001). Further, cribriform cancer was associated with amorphous morphology and yellow color. Morphology may be a useful endoscopically delineated parameter for differentiating intraductal lesions.      

Intracerebral penetration of carteolol hydrochloride in rats

To elucidate the penetrability of carteolol, a β-adrenoceptor antagonist (β-blocker) into the brain of rats, intracerebral and serum concentrations of the compound were determined in male rats receiving single or repetitive oral administration of carteolol hydrochloride at 30 mg/kg. The time-course of the intracerebral concentration of carteolol following single IV administration of the compound at 10 and 30 mg/kg was also studied in male rats. A high-performance liquid chromatography method was used to determine the intracerebral and serum concentrations. Following single oral dosing, the intracerebral concentration of carteolol reached a maximum of 0.074 μg/g at 2 h postdosing and declined with a half-life of 3.7 h, and the C_max and AUC of carteolol in the brain were 12.5% and 19.8% of those in serum. The intracerebral and serum concentrations of carteolol were determined in male rats receiving repetitive oral dosing of the compound once daily for 7 days. The concentration of carteolol in the brain and serum at 1 h postdosing varied within a range of 0.059–0.091 μg/g and 0.321–0.443 μg/ml, respectively, throughout the dosing period, showing no changes in the penetrability of the compound into the brain due to repeated dosing. The concentration of carteolol in the brain and serum increased in a dose-dependent manner in rats receiving a single IV administration of the compound. The elimination half-life of carteolol in the serum and brain was 0.6–0.8 h and 1.3–1.7 h, respectively, in rats following single IV dosing of the compound. The half-life in the brain was about twice as long as that in the serum. The brain to serum concentration ratio was 0.306:0.499. From the above results, it was concluded that carteolol is distributed from the circulation to the brain with low penetrability. Received: 30 October 1996/Final version: 16 December 1996     

Hemodynamic studies of portal hypertension with esophageal varices; a role of left gastric artery and vein

Hemodynamic states of portal hypertension with esophageal varices were studied by scintiphoto splenoportography (SSP) and left gastric angiographies in relation to endoscopic findings. The cases were classified into two groups by SSP. The flow of left gastric vein was hepatofugal in Group I (77.3%), and it was hepatopetal or "to and fro" in Group II (22.7%). Endoscopically, the varices were more severe in Group I than those in Group II. The diameter of left gastric vein was significantly larger in Group I. The values of K.ICG and liver function by blood analysis were also poor in Group I. Moreover, the cases with varices supplied by both left gastric artery and vein showed more severe endoscopic findings and history of hematemesis than those in the cases with varices supplied by left gastric artery alone. In conclusion, the results suggested that the flow of left gastric vein was closely related to the severity of esophageal varices.     

Takayasu arteritis: Follow-up studies for 20 years

We reviewed retrospectively 126 (5 male, 121 female) patients suffering from Takayasu arteritis who had been treated in our clinics from 1971 to 1990. The patients' ages ranged from 19 to 80yrs old (1990) with a mean age of 48.7 ± 11.8 years. HLA typing analysis in 98 patients revealed that 45 patients (47%) were confirmed as carrying the Bw52 antigen, a high result that is statistically significant as compared with that in healthy Japanese. Arteriograms (performed in 75 patients) revealed that 28 patients (37%) were affected in the aorta and its main branches by this disease (type IV by Nasu's classification) and 23 patients (31%) were affected only in the main branches (type I). The C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) improved significantly from 2.55 ± 0.28(+) and 57.0 ± 5.69 mm/hr to 0.53 ± 0.12(+) and 31.2 ± 3.45 mm/hr, respectively after treatment including steroid and antiplatelet therapy (P < 0.01).=" patients=" with=" bw52=" exhibited=" more=" severe=" inflammatory=" conditions=" than=" those=" without=" bw52.=" lung=" scintillations=" performed=" in=" 81=" patients=" showed=" pulmonary=" arterial=" lesions=" in=" 50=" patients=" (62%).=" echocardiograms=" revealed=" aortic=" regurgitation=" (ar)=" in=" 44=" patients=" (35%),=" with=" a=" significant=" difference=" noted=" between=" the=" bw52=" positive=" group=" and=" the=" bw52=" negative=" group=" [29/40=" (73%)=" versus=" 11/47=" (23%),=">P < 0.001].=" patients=" with=" bw52=" were=" prescribed=" higher=" doses=" of=" steroids=">P < 0.05)=" for=" longer=" periods=">P < 0.01)=" than=" those=" without=" bw52.=" of=" 11=" patients=" who=" died=" during=" our=" study=" period,=" 7=" died=" of=" cardiac=" complications,=" all=" of=" whom=" were=" suffering=" from=" ar.=" hla=" analysis=" performed=" in=" 6=" of=" these=" 7=" patients=" revealed=" that=" all=" carried=" the=" bw52=" antigen.=" in=" conclusion,=" the=" retrospective=" survey=" revealed=" that=" patients=" carrying=" the=" bw52=" antigen=" showed=" more=" severe=" inflammatory=" conditions=" and=" progressed=" more=" rapidly=" to=" complications=" and=" the=" fatal=" morbid=" condition,=" as=" compared=" with=" those=" without=" bw52.=" this=" suggests=" the=" important=" role=" of=" gene=" disequilibrium=" with=" this=" hla=">     

Calcitonin inhibits proton extrusion in resorbing rat osteoclasts via protein kinase A

Although calcitonin is well known to be a potent inhibitor of bone resorption, it remains unknown how it regulates osteoclastic H(+) transport. In this study, we examined the effects of calcitonin on H(+) extrusion in cultured rat resorbing osteoclasts using an intracellular pH (pHi) indicator, BCECF [2'7'-bis-(2-carboxyethyl)- 5-carboxyfluorescein]. Resorbing osteoclasts were identified by their formation of resorbing pits on calcium phosphate-coated quartz coverslips. Both basal pHi and H(+) extrusion activity were significantly higher compared to non-resorbing osteoclasts. Two types of H(+)-extruding systems were identified by pharmacological and immunocytochemical means: a bafilomycin-A(1)-sensitive and an amiloride-sensitive system [H(+) extrusion mediated by a vacuolar type proton pump (V-ATPase) and by a Na(+)/H(+) exchanger (NHE), respectively]. Calcitonin inhibited both H(+) extrusion activities in a dose-dependent manner and this action was mimicked by protein kinase A (PKA) activators, but not by protein kinase C (PKC) activators. Pretreatment with PKA inhibitors completely suppressed calcitonin-induced inhibition, whereas neither PKC inhibitors nor calcium chelators suppressed it. These results indicate that calcitonin inhibits H(+) extrusion generated by V-ATPase and NHE via PKA activation. These inhibitory mechanisms of H(+) transport by calcitonin are important for the regulation of bone resorption.