PKN, a conserved family member related to PKC, was the first protein kinase identified as a target of the small GTPase Rho. PKN is involved in various functions including cytoskeletal arrangement and cell adhesion. Furthermore, the enrichment of PKN3 mRNA in some cancer cell lines as well as its requirement in malignant prostate cell growth suggested its involvement in oncogenesis. Despite intensive research efforts, physiological as well as pathological roles of PKN3 in vivo remain elusive. Here, we generated mice with a targeted deletion of PKN3. The PKN3 knockout (KO) mice are viable and develop normally. However, the absence of PKN3 had an impact on angiogenesis as evidenced by marked suppressions of micro-vessel sprouting in ex vivo aortic ring assay and in vivo corneal pocket assay. Furthermore, the PKN3 KO mice exhibited an impaired lung metastasis of melanoma cells when administered from the tail vein. Importantly, PKN3 knock-down by small interfering RNA (siRNA) induced a glycosylation defect of cell-surface glycoproteins, including ICAM-1, integrin β1 and integrin α5 in HUVECs. Our data provide the first in vivo genetic demonstration that PKN3 plays critical roles in angiogenesis and tumor metastasis, and that defective maturation of cell surface glycoproteins might underlie these phenotypes.

A 27‐year‐old woman with panic disorder taking 20 mg olanzapine daily for 4 months was admitted to Mito Kyodo General Hospital, Mito, Ibaraki, Japan, because of disturbed consciousness with fever, hyperglycemia, hyperosmolarity and elevated creatine phosphokinase. She was diagnosed with a hyperosmolar hyperglycemic state and neuroleptic malignant syndrome. Brain magnetic resonance imaging showed transiently restricted diffusion in the splenium of the corpus callosum, with a high signal intensity on diffusion‐weighted imaging. The neurological abnormalities disappeared along with improvement of metabolic derangements, and the follow‐up magnetic resonance imaging carried out on the 26th day of admission showed complete resolution of the lesions in the splenium of the corpus callosum. These clinical and radiological features are highly suggestive of clinically mild encephalitis/encephalopathy with a reversible splenial lesion. The first case of mild encephalitis/encephalopathy with a reversible splenial lesion caused by olanzapine‐induced hyperosmolar hyperglycemic state and neuroleptic malignant syndrome is reported.

Aims/Introduction Flash and continuous glucose monitoring systems are becoming prevalent in clinical practice. We directly compared a flash glucose monitoring system (FreeStyle Libre Pro [FSL ‐Pro]) with a continuous glucose monitoring system ( iP ro2) in patients with diabetes mellitus. Materials and Methods Glucose concentrations were simultaneously measured using the FSL ‐Pro, iP ro2 and self‐monitoring blood glucose in 10 patients with diabetes mellitus, and agreement among them was assessed. Results Parkes error grid analysis showed that the 92.9 and 7.1% of glucose values measured using the FSL ‐Pro fell into areas A and B, respectively, and that 96.3, 2.8 and 0.9% of those determined using iP ro2 fell into areas A, B and C, respectively. The median absolute relative differences compared with self‐monitoring blood glucose were 8.1% (3.9–12.7%) and 5.0% (2.6–9.1%) for the FSL ‐Pro and iP ro2, respectively. Analysis of 5,555 paired values showed a close correlation between FSL ‐Pro and iP ro2 glucose values (ρ = 0.96, P < 0.01). Notably, 65.3% of all glucose values were lower for the FSL ‐Pro than the iP ro2. Median glucose values also decreased by 3.3% for the FSL ‐Pro compared with the iP ro2 (177.0 [133.0–228.0] vs 183.0 [145.0–230.0] mg/dL, P < 0.01). The difference in glucose values between the two systems was more pronounced in hypoglycemia. The median absolute relative difference between FSL ‐Pro and iP ro2 during hypoglycemia was much larger than that during euglycemia and hyperglycemia. Conclusions Both the FSL ‐Pro and iP ro2 systems are clinically acceptable, but glucose values tended to be lower when measured using the FSL ‐Pro than the iP ro2. Agreement was not close between these systems during hypoglycemia.

A case of acute‐onset type 1 diabetes mellitus concomitant with pneumonitis and vitiligo is described.

Abstract. To elucidate the involvement of cyclooxygenase (COX) in degradation of aggregated protein in diabetic glomeruli, we used streptozotocin (STZ)-induced diabetic mice and aggregated bovine serum albumin (a-BSA) as a model protein. There was a higher deposition of a-BSA in diabetic glomeruli compared to normal glomeruli 18 h after a-BSA injection at 4 and 8 weeks after STZ. Degradation of a-BSA was confirmed using isolated glomeruli. Diabetic glomeruli produced prostaglandin E 2 (PGE 2 ) more than normal glomeruli in the basal level at 8 weeks. a-BSA caused further increase of PGE 2 production in normal glomeruli, but not in diabetic glomeruli. Niflimic acid, a selective COX-2 inhibitor, reduced PGE 2 production of normal glomeruli in the a-BSA loading group, but not that in the control group. In diabetic glomeruli, niflimic acid reduced PGE 2 production in both the control group and a-BSA loading group. In normal glomeruli, a-BSA increased expressions of both COX-2 mRNA and protein. However, in diabetic glomeruli, a-BSA increased COX-2 mRNA expression but not COX-2 protein expression. These results suggest that retarded degradation of aggregated protein in diabetic glomeruli is associated with lack of further expression of COX-2 protein and further production of PGE 2 in response to aggregated protein.