Tumor-specific Activation of Mitogen-activated Protein Kinase in Human Colorectal and Gastric Carcinoma Tissues

To search for the signaling events in colorectal carcinoma relevant to its tumorigenesis, we investigated the activity of mitogen-activated protein kinase (MAPK) in human colorectal carcinoma tissues and paired normal tissues. Of 64 cases examined, approximately 75% (48 cases) showed tumor-specific activation of MAPK by in situ kinase renaturation assay, as well as in vitro kinase assay with immunoprecipitated MAPK. In addition, tumor-specific activation of MAPK was associated with the activation of MAPK kinase in the cases we examined. However, no clear correlation of MAPK activation with lymph node involvement, metastatic rate, stage, histological classification, age or sex was observed. These results suggest that the MAPK pathway is involved in colorectal tumor development, but its activation alone is not sufficient for malignant conversion. In contrast to colorectal carcinoma, gastric carcinoma tissues showed a lower rate of MAPK activation, suggesting that the signaling pathway activated in colorectal carcinoma tissues may differ in part from that of gastric carcinoma.     

Either desipramine or TMB-8 suppresses cyanide-induced norepinephrine efflux from in vivo cardiac sympathetic nerves of cats

To investigate the effect of hypoxia on endogenous norepinephrine (NE) release from cardiac sympathetic nerve ending, we administered sodium cyanide (NaCN) for 30 min into the myocardial interstitial space through a dialysis probe and measured dialysate NE levels. During the NaCN perfusion, a marked and concentration-dependent increase in dialysate NE was observed. This cyanide-induced NE response was suppressed by pretreatment with despiramine (a membraneous NE transport inhibitor). Furthermore, the cyanide-induced NE response was suppressed by pretreatment with TMB-8 (intracellular Ca(2+) antagonist) but unaffected by omega-conotoxin GVIA (NE releasing inhibitor). Our data suggest that two (desipramine or TMB-8 suppressive) mechanisms contributed to the amount of NE efflux induced by cyanide in in vivo cardiac sympathetic nerve.     

Local epinephrine release in the rabbit myocardial interstitium in vivo

Although several investigations have suggested cardiac epinephrine (Epi) release, local Epi release in the myocardial interstitium in vivo has not been measured. Using cardiac microdialysis in the rabbit, we measured dialysate Epi and norepinephrine (NE) concentrations as indices of myocardial interstitial Epi and NE levels, respectively. Exocytotic release induced by local administration of KCl (100 mM) through the dialysis probe increased Epi to 24.2 +/- 13.2 pg/ml from a control value of 3.2 +/- 3.6 pg/ml (P < 0.01, n = 6). Non-exocytotic release induced by the local administration of tyramine (10 microg/ml) also increased Epi to 34.6 +/- 15.3 pg/ml (p < 0.05 from control, n = 6). We conclude that Epi can be released via both exocytotic and non-exocytotic release mechanisms from the heart.     

Chronological changes in cerebral air embolism that occurred during continuous drainage of infected lung bullae

We present a 43-year-old man with cerebral air embolism that occurred during continuous drainage of infected lung bullae. This complication is extremely rare, and may have been caused by the passage of air into the pulmonary venous circulation through a bronchovenous fistula and/or damaged pulmonary vessels. Air densities were demonstrated along the right frontal gyri on a CT performed 1 h after the onset of embolism, then moved to the deep cortex after 2.5 h. Three days later, a cortical infarct accompanied with extensive white matter edema in the right frontal lobe was confirmed by MRI. These CT and MRI findings may indicate the passage of intravascular air from the superficial to the deep cortex and subsequent cerebral infarction.     

Vaccination of dendritic cells loaded with interleukin-12-secreting cancer cells augments in vivo antitumor immunity: characteristics of syngeneic and allogeneic antigen-presenting cell cancer hybrid cells.

Cancer immunotherapy by fusion of antigen-presenting cells and tumor cells has been shown to induce potent antitumor immunity. In this study, we characterized syngeneic and allogeneic, murine macrophage/dendritic cell (DC)-cancer fusion cells for the antitumor effects. The results showed the superiority of allogeneic cells as fusion partners in both types of antigen-presenting cells in an in vivo immunotherapy model. A potent induction of tumor-specific CTLs was observed in these immunized conditions. In addition, the immunization with DC-cancer fusion cells was better than that with macrophage-cancer fusion cells. Both syngeneic and allogeneic DC-cancer fusion cells induced higher levels of IFN-gamma production than macrophage-cancer fusion cells. Interestingly, allogeneic DC-cancer fusion cells were superior in that they efficiently induced Th1-type cytokines but not the Th2-type cytokines interleukin (IL)-10 and IL-4, whereas syngeneic DC-cancer fusion cells were powerful inducers of both Th1 and Th2 cytokines. These results suggest that allogeneic DCs are suitable as fusion cells in cancer immunotherapy. To further enhance the antitumor immunity in the clinical setting, we prepared DCs fused with IL-12 gene-transferred cancer cells and thus generated IL-12-secreting DC-cancer fusion cells. Immunization with these gene-modified DC-cancer fusion cells was able to elicit a markedly enhanced antitumor effect in the in vivo therapeutic model. This novel IL-12-producing fusion cell vaccine might be one promising intervention for future cancer immunotherapy.     

Whole‐exome sequencing and host cell reactivation assay lead to a diagnosis of xeroderma pigmentosum group D with mild ultraviolet radiation sensitivity

A case of xeroderma pigmentosum (XP) group D in a 39‐year‐old Japanese man is reported. The patient had suffered from moderate to severe solar sensitivity and freckle‐like pigmented macules in sun‐exposed areas since 6 years of age, and developed skin malignancies such as squamous cell carcinoma, actinic keratosis, Bowen’s disease and basal cell carcinoma. The minimal erythema dose for ultraviolet (UV) radiation was decreased with a delayed peak reaction. The level of unscheduled DNA synthesis of fibroblasts from the patient was 70% of normal, while they expressed POLH, a gene product responsible for the XP variant. Whole‐exome sequencing indicated that the patient harbored a homozygous mutation of c.1802G>T, p.Arg601Leu in ERCC2. A genetic complementation test was carried out by host cell reactivation assay, which showed that the patient’s fibroblasts recovered only when they were transfected with XPD cDNA, confirming the diagnosis of XP‐D. Arg601Leu mutation in ERCC2 may be related to mild UV radiation sensitivity and moderate skin lesions.     

Risk factors for acetabular retroversion in developmental dysplasia of the hip: does the Pemberton osteotomy contribute?

BackgroundThe purpose of this study was to investigate residual acetabular retroversion after skeletal maturity in patients with Pemberton osteotomy.Patients and methodsWe compared 40 hips in 36 patients treated with a Pemberton osteotomy (Pemberton group) and 30 hips in 26 patients treated only with a Pavlik harness (Rb group) for developmental dysplasia of the hip. The average age at operation in the Pemberton group was 94.5 months and the follow-up duration was 151.8 months. Radiographic parameters included the acetabular index (a angle) and the center-edge angle of Wiberg, preoperatively and at skeletal maturity. We examined the crossover sign (COS) at the latest follow-up as a sign of acetabular retroversion (AR). We compared the parameters between the two groups and examined the risk factors for acetabular retroversion using a multivariate Cox model.ResultA COS (+) was significantly more frequent in the Pemberton group compared to the Rb group [15 hips (37.5 %) vs 3 hips (10 %); p = 0.0077]. In the Pemberton group, the average age at operation in COS (+) hips was significantly older than that in COS (—) hips (126.9 vs 72.8 months; p = 0.0005). The preoperative α angle did not vary between hips with and without COS; however, the postoperative α angle was significantly smaller in COS (+) hips. A multiple logistic regression analysis for prediction of COS (+) showed that the age at operation and the amount change of α angle were significant predictors for COS (+) hips. The cut-off of the age at operation was 7 years and 9 months old.ConclusionsAR was present in 37.5 % of the hips in the Pemberton group after skeletal maturity. Remodeling of acetabular version was observed in younger patients; however, hips in older patients (> 8 years) at the time of operation and greater degrees of correction tended to result in AR.