Feeding behavior and ambulatory activity in rats with D-galactosamine-induced hepatic failure.

This study was undertaken to investigate changes in feeding behavior and ambulatory activity, in rats with D-galactosamine (D-GAL)-induced hepatic failure. D-GAL was administered (1000 mg/kg) IP at 1800, just before the dark phase. The first significant decrease of ambulatory activity in rats with hepatic failure was observed between 0000 and 0300 h. A significant increase in drinking behavior was observed between 1800 and 2100 h, and a significant decrease was observed between 2100 and 0300 h. A significant decrease in food intake occurred between 1800 and 2400 h. Thereafter, there was no difference in food intake. In conclusion, we demonstrated significant changes in ambulatory activity, drinking behavior and food intake produced by D-GAL. A wide variation in systems, including monoamine turnover, and amino acid disturbance could be expected in these animals, and such changes might also have contributed to the results observed.     

No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients

Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc.     

Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia

Noonan syndrome (NS) is characterized by short stature, characteristic facial features, and heart defects. Recently, missense mutations of PTPN11, the gene encoding protein tyrosine phosphatase (PTP) SHP-2, were identified in patients with NS. Further, somatic mutations in PTPN11 were detected in childhood leukemia. Recent studies showed that the phosphatase activities of five mutations identified in NS and juvenile myelomonocytic leukemia (JMML) were increased. However, the functional properties of the other mutations remain unidentified. In this study, in order to clarify the differences between the mutations identified in NS and leukemia, we examined the phosphatase activity of 14 mutants of SHP-2. We identified nine mutations, including a novel F71I mutation, in 16 of 41 NS patients and two mutations, including a novel G503V mutation, in three of 29 patients with leukemia. Immune complex phosphatase assays of individual mutants transfected in COS7 cells showed that ten mutants identified in NS and four mutants in leukemia showed 1.4-fold to 12.7-fold increased activation compared with wild-type SHP-2. These results suggest that the pathogenesis of NS and leukemia is associated with enhanced phosphatase activity of mutant SHP-2. A comparison of the phosphatase activity in each mutant and a review of previously reported cases showed that high phosphatase activity observed in mutations at codons 61, 71, 72, and 76 was significantly associated with leukemogenesis.     

Indications for retrograde cystourethrography in trauma

Injuries to the lower genitourinary tract may occur with penetrating or severe blunt lower abdominal trauma. Commonly associated findings are pelvic fractures and gross hematuria or a bloody urethral discharge. Retrograde cystourethrography should be performed in all cases of penetrating trauma when lower genitourinary tract injury is suspected. We recommend retrograde urethrography in male patients with a pelvic fracture or significant lower abdominal or perineal trauma without a fracture when associated with gross hematuria, a bloody urethral discharge, inability to void, swelling, ecchymosis or hematoma of the perineum or penis, or a "high-riding" or boggy prostate. Cystography should follow urethrography after a urethral injury has been excluded.     

Preservation of pancreas in the University of Wisconsin solution supplemented with AP39 reduces reactive oxygen species production and improves islet graft function

Ischemia-reperfusion injury (IRI) results in increased rates of delayed graft function and early graft loss. It has recently been reported that hydrogen sulfide (H₂S) protects organ grafts against prolonged IRI. Here, we investigated whether the preservation of pancreas in University of Wisconsin (UW) solution supplemented with AP39, which is a mitochondrial-targeted H₂S donor, protected pancreatic islets against IRI and improved islet function. Porcine pancreata were preserved in the UW solution with AP39 (UW + AP39) or the vehicle (UW) for 18 h, followed by islet isolation. The islet yields before and after purification were significantly higher in the UW + AP39 group than in the UW group. The islets isolated from the pancreas preserved in UW + AP39 exhibited significantly decreased levels of reactive oxygen species (ROS) production and a significantly increased mitochondrial membrane potential as compared to the islets isolated from the pancreas preserved in the vehicle. We found that the pancreas preserved in UW + AP39 improved the outcome of islet transplantation in streptozotocin-induced diabetic mice. These results suggest that the preservation of pancreas in UW + AP39 protects the islet grafts against IRI and could thus serve as a novel clinical strategy for improving islet transplantation outcomes.     

Functional transition: Inconsistently parallel to the increase in future liver remnant volume after preoperative portal vein embolization

BACKGROUNDPreoperative portal vein embolization (PVE) is a widely used strategy to enable major hepatectomy in patients with insufficient liver remnant. PVE induces hypertrophy of the future liver remnant (FLR) and a shift of the functional reserve to the FLR. However, whether the increase of the FLR volume (FLRV) corresponds to the functional transition after PVE remains unclear.AIMTo investigate the sequential relationship between the increase in FLRV and functional transition after preoperative PVE using 3-dimensional (3D) computed tomography (CT) and ^99mTc-galactosyl-human serum albumin (^99mTc-GSA) single-photon emission computed tomography (SPECT) fusion images. METHODSThirty-three patients who underwent major hepatectomy following PVE at the Department of Gastroenterological Surgery I, Hokkaido University Hospital between October 2013 and March 2018 were enrolled. Three-phase dynamic multidetector CT and ^99mTc-GSA SPECT scintigraphy were performed at pre-PVE, and at 1 and 2 wk after PVE; 3D ^99mTc-GSA SPECT CT-fused images were constructed from the Digital Imaging and Communications in Medicine data using 3D image analysis system. Functional FLRV (FFLRV) was defined as the total liver volume × (FLR volume counts/total liver volume counts) on the 3D ^99mTc-GSA SPECT CT-fused images. The calculated FFLRV was compared with FLRV.RESULTSFFLRV increased by a significantly larger extent than FLRV at 1 and 2 wk after PVE (P < 0.01). The increase in FFLRV and FLRV was 55.1% ± 41.6% and 26.7% ± 17.8% (P < 0.001), respectively, at 1 wk after PVE, and 64.2% ± 33.3% and 36.8% ± 18.9% (P < 0.001), respectively, at 2 wk after PVE. In 3 of the 33 patients, FFLRV levels decreased below FLRV at 2 wk. One of the three patients showed rapidly progressive fatty changes in FLR. The biopsy at 4 wk after PVE showed macro- and micro-vesicular steatosis of more than 40%, which improved to 10%. Radical resection was performed at 13 wk after PVE. The patient recovered uneventfully without any symptoms of pos-toperative liver failure.CONCLUSIONThe functional transition lagged behind the increase in FLRV after PVE in some cases. Evaluating both volume and function is needed to determine the optimal timing of hepatectomy after PVE.     

Does the washout phenomenon of Tc-99m HM-PAO correlate to the “Filling-in” phenomenon of I-123 IMP with brain SPECT?

Summary Using SPECT, the time course of brain uptake was compared between N-isopropyl-p-[I-123]-iodoamphetamine (I-123 IMP) and Tc-99m d,l hexamethyl-propyleneamine oxime (Tc-99m HM-PAO). Of 14 patients with cerebrovascular disease showing areas of the filling-in phenomenon (i.e. delayed uptake) with I-123 IMP brain SPECT, 7 exhibited persistent defects with Tc-99m HM-PAO (Group I), and 7 showed early washout after the initial uptake (Group II). The filling-in of I-123 IMP did not always correlate to the washout region of Tc-99m HM-PAO. The temporal changes were also confirmed by semiquantitative analysis. While the filling-in of I-123 IMP was affected by many factors, the washout of Tc-99m HM-PAO was attributed to significant reduction of Tc-99m HM-PAO in the plasma. Delayed imaging of the brain with Tc-99m HM-PAO using SPECT may give a more accurate estimate of regional cerebral blood flow in cerebrovascular disease, because it should be lees effected by cerebral blood volume.     

Effect of irradiation on transforming growth factor-β secretion by malignant glioma cells

Glioblastoma cells secrete transforming growth factor- (TGF-), whichhas a variety of immunosuppressive properties. We investigatedthe effect of irradiation TGF- secretion by malignantglioma cells. Three malignant glioma cell lines (T98G,A172, KG-1-C) were cultured and irradiated using 10and 50 Gy Linac radiation. After further culturefor 36 hours in serum-free culture medium, thesupernatants were collected. The TGF- activity in theculture supernatants was determined using a specific bioassay.The levels of the active form and totalTGF- in the supernatants from irradiated malignant gliomacells decreased compared to those from un-irradiated cells.However, since irradiation inhibited the growth of tumorcells, the amount of TGF- secretion per cellin irradiated cells tended to increase after irradiation.These results suggest that malignant glioma cells canstill secrete TGF- and activate latent TGF- evenafter large dose irradiation, despite the inhibition oftumor growth.     

Upward migration of the L-P shunt catheter into the cranial base

A rare complication of upward migration of the L-P shunt catheter into the cranial base is reported. A 59-year-old female with hydrocephalus underwent L-P shunt with a one-piece catheter. The catheter was secured with a clip but migrataed up to the cranial base without the clip becoming detached from the catheter. We assume that the catheter slipped at the position of the clip as the result of a strong force produced by lumbar movements, and that the clip may have acted like an one-way valve to push the catheter into the spinal canal. To prevent such a complication, we should tighten the clip as firmly as possible and use more clips, or use another type of clip which prevents slipping of a one-piece catheter such as the one described by Imaizumi et al.