PAG3/Papalpha/KIAA0400, a GTPase-activating protein for ADP-ribosylation factor (ARF), regulates ARF6 in Fcgamma receptor-mediated phagocytosis of macrophages

The Fcgamma receptor (FcgammaR)-mediated phagocytosis of macrophages is a complex process where remodeling of both the actin-based cytoskeleton and plasma membrane occur coordinately. Several different families of small GTPases are involved. We have isolated a GTPase-activating protein (GAP) for ADP-ribosylation factor (ARF), paxillin-associated protein with ARFGAP activity (PAG)3/Papalpha/KIAA0400, from mature monocytes and macrophage-like cells. Mammalian ARFs fall into three classes, and the class III isoform (ARF6) has been shown to be involved in FcgammaR-mediated phagocytosis. Here we report that PAG3 is enriched together with ARF6 and F-actin at phagocytic cups formed beneath immunoglobulin G-opsonized beads in P388D1 macrophages, in which overexpression of ARF6, but not ARF1 (class I) or ARF5 (class II), inhibits the phagocytosis. Overexpression of PAG3, but not its GAP-inactive mutant, attenuated the focal accumulation of F-actin and blocked phagocytosis, although surface levels of the FcgammaRs were not affected. Other ubiquitously expressed ARFGAPs, G protein-coupled receptor kinase interactors GIT2 and GIT2-short/KIAA0148, which we have shown to exhibit GAP activity for ARF1 in COS-7 cells, did not accumulate at the phagocytic cups or inhibit phagocytosis. Moreover, cooverexpression of ARF6, but not ARF1 or ARF5, restored the phagocytic activity of PAG3-overexpressing cells. We propose that PAG3 acts as a GAP for ARF6 and is hence involved in FcgammaR-mediated phagocytosis in mouse macrophages.     

Nonsecretory primary plasma cell leukemia successfully treated with VAD and MP therapy

A 78-year-old woman was admitted to our hospital because of lumbago and appetite loss. Blood analysis revealed anemia, hypercalcemia and circulating plasma cells. Bone marrow aspiration showed an elevated ratio (43%) of plasma cells, which expressed CD38 in the absence of CD19 and CD56 expression. Spinal MR imaging revealed multiple compression fractures and suggested diffuse invasion of plasma cells into the spinal bodies. No M-protein was detectable in serum or urine by immunoelectrophoresis and immunofixation, but cytoplasmic M-protein (IgG-kappa) was detected by enzyme antibody staining. On the basis of the history and data, nonsecretory primary plasma cell leukemia was diagnosed. First, the patient was given modified VAD therapy (vincristine, doxorubicin, and prednisolone) and complete remission was obtained. Then MP therapy (melphalan and prednisolone) was instituted, and remission has since been maintained for 11 months. Like many other cases of primary plasma cell leukemia, this case suggests that CD56 may act as an adhesion molecule between neoplastic plasma cells and bone marrow stromal cells. Our experience with this exceedingly rare case suggests the superiority of combination chemotherapy as an induction therapy and the effectiveness of MP therapy as maintenance therapy for this disease.     

l-[1-(13)C]Alanine is a useful substance for the evaluation of liver function

BACKGROUND: Using a rat model of hepatectomy, we investigated whether the severity of hepatopathy could be quantitatively measured from changes in expiratory (13)CO(2) levels after intravenous administration of l-[1-(13)C]alanine. MATERIALS AND METHODS: Under nembutal anesthesia, 20 mg/kg l-[1-(13)C]alanine was administered to rats via the femoral vein, and expiratory (13)CO(2) levels were measured for 15 min. Then, 30, 70, or 90% hepatectomy was performed. In the control group, simple laparotomy was performed. A breath test was conducted 20 min after laparotomy. We examined the correlation of total (13)CO(2) output (S) or single point (13)CO(2) level (SP) every 1 min for 15 min with liver weight/body weight (LW/BW) (%). RESULTS: In the control group, the breath test graph showed a specific peak level about 3 min after administration, but in all groups undergoing hepatectomy, it did not show any peak level during measurement. The correlation coefficient between S(12--15) after l-[1-(13)C]alanine administration and LW/BW was 0.902 (P < 0.0001). The correlation coefficient between SP(7) after l-[1-(13)C]alanine administration and LW/BW was highest, 0.908 (P < 0.0001). The severity of hepatopathy could also be evaluated, with significant differences in S(12-14) compared to control when the volume of resected liver was 30% or greater, but there was no significant difference between the groups undergoing 70 and 90% hepatectomy. However, the severity of hepatopathy could be evaluated, with significant differences in S(15) and SP(7) in all comparisons between groups. CONCLUSION: In the breath test with intravenously administered l-[1-(13)C]alanine, the severity of hepatopathy could be quantitatively evaluated in a short period by measuring S(15) and SP(7).     

Effectiveness of using low rate fluoroscopy to reduce an examiner's radiation dose during lumbar nerve root block

Background

Long-term exposure to radiation can lead to gene mutations and increase the risk of cancer. Low rate fluoroscopy has the potential to reduce the radiation exposure for both the examiner and the patient during various fluoroscopic procedures. The purpose of this study was to evaluate the impact of low rate fluoroscopy on reducing an examiner's radiation dose during nerve root block.

Decline in estimated glomerular filtration rate is associated with risk of end-stage renal disease in type 2 diabetes with macroalbuminuria: an observational study from JDNCS

Background

There is increased interest in surrogate endpoints for clinical trials of chronic kidney disease.

Methods

In this nationwide observational study of 456 patients with type 2 diabetes and clinically suspected diabetic nephropathy followed for a median of 4.2 years, we evaluated the association between estimated glomerular filtration rate (eGFR) and albuminuria at baseline or during follow-up and risk of ESRD.

Results

Low eGFR (<60 mL/min/1.73 m²) and macroalbuminuria at enrollment were independently associated with risk of ESRD. In patients with macroalbuminuria, both ≤?50% change and ?50 to ?30% change in eGFR over 1 and 2 years were predictive of ESRD. The higher cut point (≥50% decline in eGFR) was more strongly predictive but less common. Remission of macroalbuminuria to normo-/microalbuminuria at 1 and 2 years was associated with a lower incidence of ESRD than no remission; however, it was not a determinant for ESRD independently of initial eGFR and initial protein-to-creatinine ratio.

Conclusion

These results suggest that a ≥30% decline in eGFR over 1 or 2 years adds prognostic information about risk for ESRD in patients with type 2 diabetes and macroalbuminuria, supporting the consideration of percentage decline in eGFR as a surrogate endpoint among macroalbuminuric cases in type 2 diabetes. On the other hand, our study suggests that additional analyses on the relationship between remission of macroalbuminuria and risk of ESRD are needed in type 2 diabetes.

     

Anesthetic management for surgery of the ankle joint fracture in a patient with Ebstein's anomaly

The authors describe the successful anesthetic management of a patient with Ebstein's anomaly and Wolff-Parkinson-White syndrome who underwent repair for foot joint fracture. Anesthesia was provided by combined spinal-epidural block to minimize hemodynamic changes which cause an increase in right-to-left shunt and hypoxemia. We estimated hemodynamic status using radial arterial pressure, central venous pressure and ECG from the start of anesthesia. During anesthesia, his vital signs were unchanged to any significant degree. The recovery was rapid and the postoperative course was uneventful.     

A minimally invasive multiple percutaneous drainage technique for acute necrotizing pancreatitis

BACKGROUND:

In approximately 20% of patients, necrotizing pancreatitis is complicated with severe acute pancreatitis, with high morbidity and mortality rates. Minimally invasive step-up approach is both safe and effective, but sometimes requires multiple access sites.

METHODS:

A 62-year-old woman was admitted with diabetic ketoacidosis, and initial computed tomography (CT) revealed no evidence of acute pancreatitis. She was clinically improved with insulin therapy, fluid administration, and electrolyte replacement. However, on the 14^th day of admission, she developed a high-grade fever, and CT demonstrated evidence of acute necrotizing pancreatitis with a large collection of peripancreatic fluid. Percutaneous transgastric drainage was performed and a 14 French gauge (Fr) pigtail catheter was placed 1 week later, which drained copious pus. Because of persistent high-grade fever and poor clinical improvement, multiple 8 and 10 Fr pigtail catheters were placed via the initial drainage route, allowing the safe and effective drainage of the extensive necrotic tissue that was occupying the bilateral anterior pararenal space.

RESULTS:

After drainage, the patient recovered well and the last catheter was removed on day 123 of admission.

CONCLUSIONS:

Multiple percutaneous drainage requires both careful judgment and specialist skills. The perforation of the colon and small bowel as well as the injury of the kidney and major vessels can occur. The current technique appears to be safe and minimally invasive compared with other drainage methods in patients with extended, infected necrotic pancreatic pseudocysts.KEY WORDS: Percutaneous drainage, Acute necrotizing pancreatitis, Minimally invasive technique     

Assessment of sublingual PCO2 during selective cerebral perfusion

We monitored sublingual tissue PCO2 (PSLCO2) continuously with an ISFET (ion-sensitive field effect transistor) based PCO2 sensor during and after surgical treatment for descending aortic aneurysm. Using femoro-femoral bypass and a beating heart technique, distal end of aneurysm was clamped and then selective cerebral perfusion was performed into the left subclavian and left common carotid arteries. Aneurysmectomy and reconstructive surgery were carried out with proximal end of the left common carotid artery being clamped. Upon starting selective cerebral perfusion, PSLCO2 increased abnormally. PSLCO2 increased from 38 mmHg just after induction of anesthesia to the maximum value of 87 mmHg during selective cerebral perfusion. Three hours after arriving in the intensive care unit, the patient developed convulsion and anisocoria and the computed tomography showed cerebral infraction. Since the blood flow to the tongue is fed through the internal and external carotid arteries, the increase in PSLCO2 is supposed to be caused by the decrease of blood flow to the tongue during selective cerebral perfusion. The monitoring of PSLCO2 may be a useful method to estimate the brain blood flow during selective cerebral perfusion.