Moyamoya syndrome occurred in a girl with an inactive systemic lupus erythematosus.

We report the case of a 17-year-old Korean girl with systemic lupus erythematosus (SLE) who presented with sudden weakness of the right-sided extremities and dysarthria. Oral prednisolone was being taken to control SLE. Results of clinical and laboratory examinations did not show any evidence of antiphospholipid syndrome or thromboembolic disease nor SLE activity. Cerebral angiography showed stenosis of the left internal carotid artery and right anterior cerebral artery with accompanying collateral circulation (moyamoya vessels). After the patient underwent bypass surgery on the left side, she recovered from the neurological problems and did not experience any additional ischemic attack during the 14-month follow-up period. This case represents an unusual association between moyamoya syndrome and inactive SLE (inactive for a relatively long interval of 2 years) in a young girl.

Rosiglitazone inhibits proliferation of renal proximal tubular cells via down-regulation of ERK and Akt.

Rosiglitazone has been reported to exert the protective effect against acute renal failure in animal models. However, the underlying mechanisms by which it protects the damaged kidney cells are poorly understood. The present study was therefore undertaken to examine the effect of rosiglitazone on cell proliferation and to determine its molecular mechanism in opossum kidney (OK) cells, an established renal proximal tubular cell line. Rosiglitazone treatment inhibited cell proliferation in a dose- and time-dependent manner, and such effects were not associated with induction of cell death. The anti-proliferative effect of rosiglitazone was accompanied by the cell cycle arrest at the G1 phase. Western blot analysis data showed that rosiglitazone caused down-regulation of extracellular signal-regulated kinase (ERK) and Akt pathway. Transfection of constitutively active forms of MEK (an upstream kinase of ERK) and Akt prevented the proliferation inhibition induced by rosiglitazone. Rosiglitazone facilitated the recovery of cells after cisplatin-mediated injury. Taken together, these data suggest that rosiglitazone induces inhibition of cell proliferation through ERK and Akt-dependent cell cycle arrest at the G1 phase. The cell cycle arrest may play a protective role in kidney cells by preventing injured cells from progressing in the cell cycle.

Delayed diagnosis of ureteropelvic junction avulsion in a child owing to unstable hemodynamics.

BACKGROUND: A 7-year-old previously healthy girl was injured in a traffic accident and presented to the emergency room with abdominal pain, microscopic hematuria, and wide skin defects and deep lacerations on the left flank, left upper abdomen, and right inguinal area. Initial CT of the abdomen was unremarkable. 3 weeks later, the patient complained of abdominal distension, left flank pain, and fever. INVESTIGATIONS: Blood and urine tests, CT of the abdomen, chest X-ray, antegrade pyelography, intravenous urography, renal ultrasonography and diuretic renal scan. DIAGNOSIS: Complete avulsion injury of the left ureteropelvic junction. MANAGEMENT: The patient underwent 11 plastic reconstructive surgeries, including a skin grafting operation. A percutaneous nephrostomy was performed for temporary diversion. After complete healing of the left flank wound, open pyeloplasty was performed to create a ureteropelvic anastomosis with stent. The patient was discharged 1 week after surgery and the stent was removed 5 weeks later. 5 years after pyeloplasty, her renal function was normal and she had experienced no complications.

Differential effect of FGF and PDGF on cell proliferation and migration in osteoblastic cells.

It has been known that growth factors such as fibroblast growth factor (FGF) and platelet-derived growth factor (PDGF) can promote proliferation and migration in a variety of cell types including osteoblastic cells. However, the mechanism underlying their action has not been clearly defined. The present study was undertaken to examine the effect of FGF and PDGF on cell proliferation and migration and to determine the role of extracellular signal-regulated kinase (ERK) and Akt in action of FGF and PDGF in osteoblastic cells. FGF enhanced proliferation in a dose- and time-dependent manner, whereas it did not affect cell migration. FGF induced a transient activation of ERK, but not Akt, which was inhibited by an inhibitor of MEK, the upstream kinase of ERK, but not by inhibitors of PI3K/Akt (LY294002), epidermal growth factor receptor (EGFR, AG1478), and Src (PP2). FGF-induced proliferation was inhibited by inhibitors of MEK/ERK and Src pathways. Exposure of cells to FGF stimulated transition of cell cycle from the G1 phase to S phase and increased phosphorylation of Rb. FGF-induced phosphorylation of Rb was attenuated by inhibitors of MEK/ERK and Src pathways. Cell migration studies indicated that PDGF stimulated migration, but it had no effect on cell proliferation. PDGF induced activation of ERK and Akt. The ERK activatin was inhibited by the Src inhibitor and the Akt activation was inhibited by inhibitors of EGFR and Src. PDGF-induced migration was inhibited by inhibitors of MEK/ERK, PI3K/Akt, EGFR and Src pathways. Taken together, these findings suggest that the MEK/ERK and Src pathways play an important role in the FGF-induced proliferation and signaling pathways involving MEK/ERK, EGFR, Src and PI3K/Akt mediate the PDGF-induced migration. These data are of importance in understanding the roles of these growth factors in osteoblastic cell proliferation and migration.

EGFR-dependent ERK activation triggers hydrogen peroxide-induced apoptosis in OK renal epithelial cells.

Oxidative stress induces activation of extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase families. However, it is unclear in renal epithelial cells whether the ERK activation is involved in cell survival or cell death in H2O2-treated cells. The present study was undertaken to determine the role of the ERK activation in H2O2-induced apoptosis of renal epithelial cells using opossum kidney (OK) cells, an established proximal tubular epithelial cell line. H2O2 resulted in a time- and dose-dependent apoptosis of OK cells. H2O2 treatment caused marked sustained activation of ERK. The ERK activation was prevented by PD98059 and U0126, inhibitors of ERK1/2 upstream kinase MEK1/2. Apoptosis caused by H2O2 was prevented by U0126. Transient transfection with constitutive active MEK1 increased the H2O2-induced apoptosis, whereas transfection with dominant-negative mutants of MEK1 decreased the apoptosis. H2O2 produced hyperpolarization of mitochondrial membrane potential and activation of caspases-3. H2O2-induced ERK activation was inhibited by the Src family selective inhibitor PP2 and the epidermal growth factor receptor inhibitor AG1478. The presence of AG1478, but not PP2, prevented H2O2-induced cell death. Taken together, our findings suggest that the ERK activation mediated by epidermal growth factor receptor plays an active role in inducing H2O2-induced apoptosis of OK cells and functions upstream of mitochondria-dependent pathway to initiate the apoptotic signal.

Hematuria and proteinuria in a mass school urine screening test.

A total of 1,044 school children identified with hematuria and/or proteinuria during a mass school urine screening test were referred to pediatric nephrologists at 13 hospitals in Korea. These children had isolated hematuria (IH) (60.1%), isolated proteinuria (IP) (26.4%: transient, 19.6%; orthostatic, 4.9%; persistent, 1.9%) or combined hematuria and proteinuria (CHP) (13.5%). The patient's history, physical examination, laboratory tests, kidney ultrasound and Doppler ultrasonography were obtained. Renal biopsies were performed on 113 children who showed severe proteinuria, hypertension, abnormal renal function, family history of chronic renal disease, systemic diseases or persistent hematuria and/or proteinuria for more than 12 months. IgA nephropathy (IgAN), thin basement membrane nephropathy (TBMN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), other GN, Alport syndrome and lupus nephritis were detected. IgAN and TBMN were the most common causes in the CHP group and IH group, respectively. Abnormal findings on the renal ultrasound with or without Doppler ultrasonography were noted in 147 cases (suspected nutcracker phenomenon, 65; increased parenchymal echogenicity, 40; hydronephrosis, 15). This study showed that the use of a mass school urine screening program can detect chronic renal disease in its early stage and recommends that more attention should be paid to identifying those children with CHP and massive proteinuria. A school urine screening program can detect chronic renal disease in its early stage. When mass screening is used, the initial aggressive diagnostic procedures such as renal biopsy are not needed. In addition, a regular follow-up for those children with IH and IP is certainly warranted.

Enhanced protection against HSV lethal challenges in mice by immunization with a combined HSV-1 glycoprotein B:H:L gene DNAs.

The effectiveness of a cocktailed HSV-1 three-glycoprotein B, H, and L gene vaccine in comparison to individual glycoprotein gene vaccines was studied with regard to protecting against the HSV-1 infection. Three glycoprotein gene recombinant DNA vaccines, which produced the corresponding glycoproteins in Vero cells, were constructed using a CMV promoter. The cocktailed DNA vaccines were prepared by combining all three genes. The titers of neurtalizing antibody following the immunization of the five vaccines were KOS(1/1024)>B:H:L=B(1/512)>H:L(1/64)>H(1/16) genes. The mice, which were immunized with L gene alone failed to induce enough neutralizing antibody. The CTL activity was rated as KOS (95%)>B:H:L (80%)>B(60%)>H:L(50%)> H (35%) gene vaccines at an E:T ratio of 50:1. The H gene alone or L gene vaccine alone induced little CTL activity. The protection rates of the DNA-vaccinated mice against the lethal intraperitoneal (i.p.) or i.m challenges were shown as KOS>B:H:L>B>H:L>H gene vaccines, and the protection activity depended on the lethal dosage of the challenging virus, which are inversely proportional to each other. Compared with the mice, which were vaccinated with individual DNA vaccines, the mice, which were vaccinated with the cocktailed three-gene vaccine, were shown to be better protected against the lethal challenging doses. It can be concluded that vaccination with the cocktailed three gene vaccines is more effective in protecting mice from the viral challenge and the protection rate varies inversely with the amount of lethal challenging dose used, although all DNA vaccines failed to block the latent infection in sensory nerves.