Abstract Purpose Disuse atrophy of the lower limbs of patients with consciousness disturbance has often been recognized as “an unavoidable consequence,” such that the mechanism was not investigated ...diligently. In this study, we examined the preventive effects of electrical muscle stimulation (EMS) against disuse atrophy of the lower limbs in patients in coma after stroke or traumatic brain injury in the intensive care unit. Materials and Methods We evaluated changes in cross-sectional area of lower limb muscles weekly with computed tomography in 6 control group patients and 9 EMS group patients. Electrical muscle stimulation was performed daily from day 7 after admission. We evaluated the anterior thigh muscle compartment, posterior thigh muscle compartment, anterior leg muscle compartment, and posterior leg muscle compartment. Results In the control group, the decrease in cross-sectional area progressed in all compartments every week ( P < .0001). Cross-sectional areas of all compartments at day 14 were significantly decreased in the control group compared with those in the EMS group at day 7 ( P < .001). We were able to limit the rate of muscle atrophy as measured in the cross-sectional areas to within 4% during the period of EMS (days 7-42) in 5 patients. The difference between the control and the EMS groups was statistically significant ( P < .001). Conclusion Electrical muscle stimulation is effective in the prevention of disuse muscle atrophy in patients with consciousness disorder.
In our previous study of patients with early-phase severe traumatic brain injury (TBI), the anti-inflammatory interleukin (IL)-10 concentration was lower in cerebrospinal fluid (CSF) than in serum, ...whereas proinflammatory IL-1beta and tumor necrosis factor (TNF)-alpha concentrations were higher in CSF than in serum. To clarify the influence of additional injury on this disproportion between proinflammatory and anti-inflammatory mediators, we compared their CSF and serum concentrations in patients with severe TBI with and without additional injury. All 35 study patients (18 with and 17 without additional injury) had a Glasgow Coma Scale score of 8 or less upon admission. With the exception of additional injury, clinical characteristics did not differ significantly between groups. CSF and serum concentrations of two proinflammatory mediators (IL-1beta and TNF-alpha,) and three anti-inflammatory mediators (IL-1 receptor antagonist IL-1ra, soluble TNF receptor-I sTNFr-I, and IL-10) were measured and compared at 6 h after injury. CSF concentrations of proinflammatory mediators were much higher than the corresponding serum concentrations in both patient groups (P < 0.001). In contrast, serum concentrations of anti-inflammatory mediators were much higher than the paired CSF concentrations in patients with additional injury (P < 0.001), but serum concentrations were lower than or equal to the corresponding CSF concentrations in patients without additional injury. CSF concentrations of IL-1beta, IL-1ra, sTNFr-I, and IL-10 were significantly higher (P < 0.01 for all) in patients with high intracranial pressure (ICP; n = 11) than in patients with low ICP (n = 24), and were also significantly higher (P < 0.05 for all) in patients with an unfavorable outcome (n = 14) than in patients with a favorable outcome (n = 21). These findings indicate that increased serum concentrations of anti-inflammatory mediators after severe TBI are mainly due to additional extracranial injury. We conclude that anti-inflammatory mediators in CSF may be useful indicators of the severity of brain damage in terms of ICP as well as overall prognosis of patients with severe TBI.
Hydrochloric acid (HCl) is produced in parietal cells of gastric epithelium by a H + âK + pump. Protons are secreted into the gastric lumen in exchange for K + by the action of the H + âK + ...-ATPase. Luminal K + is essential for the operation of the pump and is thought to be supplied by unidentified K + channels localized at the apical membrane of parietal cells. In this study, we showed that histamine- and carbachol-induced
acid secretion from isolated parietal cells monitored by intracellular accumulation of aminopyrine was depressed by Ba 2+ , an inhibitor of inwardly rectifying K + channels. Among members of the inwardly rectifying K + channel family, we found with reverse transcriptase-polymerase chain reaction analyses that Kir4.1, Kir4.2 and Kir7.1 were
expressed in rat gastric mucosa. With immunohistochemical analyses, Kir4.1 was found to be expressed in gastric parietal cells
and localized specifically at their apical membrane. The current flowing through Kir4.1 channel expressed in HEK293T cells
was not affected by reduction of extracellular pH from 7.4 to 3. These results suggest that Kir4.1 may be involved in the
K + recycling pathway in the apical membrane which is required for activation of the H + âK + pump in gastric parietal cells.
A 54-year-old woman complaing of right upper abdominal pain was referred to the hospital with a diagnosis of a giant hepatocellular carcinoma (HCC) 20cm in size on admission, the HCC occupied the ...entire right and medial lobes of the liver, and contacted with the left hepatic vein. The tumor emboli advanced to the main to left branchs of portal vein (Vp4). A right trisegmentectomy, a caudate lobectomy, a removal of the tumor emboli in the portal vein, a bile duct resection and a hepaticojejunostomy were performed. During the removal of the tumor emboli, a baloon catheter inserted from the umbilical vein was used as a method of hemostasis. The postoperative course was uneventful and she was discharged from the hospital on 24th POD. However, recurrence occurred in the remnant liver two months later. Inspite of additional therapies such as intermittent, intraarterial chemotherapy with reservor and radiation, she died of recurrence ten months after the operation. Pathologically, the mass was moderately differentiated HCC with vp4 and the tumor emboli invaded the wall of the bifurcation of the portal vein. We think that this HCC revealed a rare mode of progression as HCC.
Inwardly rectifying K^+ channel, Kir4.1/KAB-2/Kir1.2, is expressed in glial cells of brain and distal tubular epithelia of kidney and is considered to participate in K^+ transport. We found that some ...subset of gastric mucosal cells of rat stomach expressed Kir4.1 mRNA by RT-PCR and in situ hybridization. By immunohistochemical analysis, Kir4.1 was found to be expressed in parietal cells. Immunoelectron microscopic examination further revealed that Kir4.1 was expressed in tubulovesicles and apical membrane of parietal cells and co-localized with H^+ /K^+ -ATPase. This suggests that Kir4.1 participates in acid secretion. Kir4.1 may supply K^+ ions to the K^+ site of H^+ /K^+ -ATPase to maintain the ATPase activity. SAP97/dlg, which contains three PDZ domains, was also found to be expressed on tubulovesicles and apical membrane of parietal cells. SAP97 could aggregate Kir4.1 on the membrane of transfected cells with SAP97 and Kir4.1. SAP97 may participate in the subcellular localization of Kir4.1 in parietal cells.
Aire controls the fate of autoreactive thymocytes (i.e., clonal deletion or development into regulatory T cells Tregs) through transcriptional control of the expression of tissue-restricted ...self-antigens (TRAs) from medullary thymic epithelial cells (mTECs) and bone marrow (BM)-derived cells. Although TRAs expressed by mTECs and BM-derived cells are suggested to complement each other to generate a full spectrum of TRAs, little is known about the relative contribution of TRAs from each component for establishment of self-tolerance. Furthermore, the precise role of Aire in specific types of Aire-expressing APCs remains elusive. We have approached these issues by generating two different types of transgenic mouse (Tg) model, which express a prefixed model self-antigen driven by the insulin promoter or the Aire promoter. In the insulin-promoter Tg model, mTECs alone were insufficient for clonal deletion, and BM-derived APCs were required for this action by utilizing Ag transferred from mTECs. In contrast, mTECs alone were able to induce Tregs, although at a much lower efficiency in the absence of BM-derived APCs. Importantly, lack of Aire in mTECs, but not in BM-derived APCs, impaired both clonal deletion and production of Tregs. In the Aire-promoter Tg model, both mTECs and BM-derived APCs could independently induce clonal deletion without Aire, and production of Tregs was impaired by the lack of Aire in mTECs, but not in BM-derived APCs. These results suggest that the fate of autoreactive thymocytes together with the requirement for Aire depend on the cell types that express self-antigens and the types of APCs involved in tolerance induction.
Choline supplies methyl groups for regeneration of methionine and the methyl donor S-adenosylmethionine in the liver. Here, we report that the catabolism of membrane phosphatidylcholine (PC) into ...water-soluble glycerophosphocholine (GPC) by the phospholipase/lysophospholipase PNPLA8-PNPLA7 axis enables endogenous choline stored in hepatic PC to be utilized in methyl metabolism. PNPLA7-deficient mice show marked decreases in hepatic GPC, choline, and several metabolites related to the methionine cycle, accompanied by various signs of methionine insufficiency, including growth retardation, hypoglycemia, hypolipidemia, increased energy consumption, reduced adiposity, increased fibroblast growth factor 21 (FGF21), and an altered histone/DNA methylation landscape. Moreover, PNPLA8-deficient mice recapitulate most of these phenotypes. In contrast to wild-type mice fed a methionine/choline-deficient diet, both knockout strains display decreased hepatic triglyceride, likely via reductions of lipogenesis and GPC-derived glycerol flux. Collectively, our findings highlight the biological importance of phospholipid catabolism driven by PNPLA8/PNPLA7 in methyl group flux and triglyceride synthesis in the liver.
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•PNPLA7 is a major lysophospholipase that produces GPC in the liver•Mice deficient in PNPLA7 or PNPLA8 show various signs of methionine insufficiency•Choline mobilized from hepatic PC by the PNPLA8-PNPLA7 axis supplies methyl groups•This PC-catabolic pathway is also linked to hepatic TG synthesis via glycerol flux
Hirabayashi et al. demonstrate that hepatic phosphatidylcholine catabolism driven by two particular members of the phospholipase A2 family, PNPLA7 and PNPLA8, mobilizes endogenous choline to replenish the methionine cycle with methyl groups. Genetic deletion of these enzymes leads to systemic abnormalities reminiscent of methyl group deficiency.
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