Clinical Effectiveness and Safety Outcomes of Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke in China.

BACKGROUNDS AND PURPOSE: This study was aimed at investigating the outcomes and predictors for the poor functional outcome after endovascular treatment (EVT) in a large, mostly Asian population. METHODS: Between January 2014 and June 2016, acute stroke patients with anterior circulation occlusion and EVT were retrospectively enrolled from 21 stroke centers in China. The main outcomes were modified Rankin Scale (0-2 as functional independence, 3-6 as poor) at 90 days, symptomatic intracranial hemorrhage (sICH) at 72 h, and death at 90 days. Logistic regression was used to identify predictors for poor functional outcome at 90 days. RESULTS: Of the 698 patients, 304 (43.6%) patients had functional independence at 90 days. The sICH rate was 15.5% (108/698) and mortality rate at 90 days was 25.4% (177/698). Age (OR 1.04, 95% CI 1.02-1.07), National Institutes of Health Stroke Scale score at admission (11-20 vs. ≤10, OR 2.38, 95% CI 1.23-4.59; ≥21 vs. ≤10, OR 3.66, 95% CI 1.72-7.80), baseline glucose level (OR 1.09, 95% CI 1.01-1.18), onset to groin puncture >6 h (OR 1.88, 95% CI 1.06-3.31), sICH (OR 15.49, 95% CI 5.16-46.43), and pneumonia (OR 3.15, 95% CI 1.86-5.32) were independent predictors of poor functional outcomes, while good recanalization (OR 0.26, 95% CI 0.13-0.54), preoperative Alberta Stroke Program Early CT Score 8-10 (OR 0.48, 95% CI 0.28-0.83), and good collateral flow (OR 0.50, 95% CI 0.32-0.79) were protective factors. CONCLUSIONS: This study provides evidence in real world to support the performance of EVT in acute anterior circulation stroke patients in Chinese population. Patients with small infarct core, successful recanalization, good collateral status, and short treatment delay without sICH or pneumonia may benefit from EVT.

Lack of improvement following endovascular therapy in patients with acute ischemic stroke.

BACKGROUND: Recent randomized trials have consistently demonstrated a clinical benefit of endovascular therapy (ET) over best medical therapy (including intravenous (IV) thrombolysis in eligible patients) or IV thrombolysis only in selected patients with acute ischemic stroke (AIS) due to proximal occlusion in the carotid territory. Previous study demonstrates that lack of improvement (LOI) at 24 hours is an independent predictor of poor outcome and death at 3 months in patients with AIS treated with IV alteplase. However, LOI at 24 hours following ET has not been studied systematically. The purpose of this study is to identify predictors of LOI at 24 hours in patients with AIS after ET as well as the relationship between LOI and unfavorable outcome at 3 months. METHODS: A total of 98 consecutive patients with AIS treated with ET in two separate stroke centers from 2010 to 2014 were retrospectively reviewed. Data on demographics, preexisting vascular risk factors, occlusion site, pre- and post-treatment modified Treatment in Cerebral Ischemia (mTICI) classification, collaterals and National Institutes of Health Stroke Scale (NIHSS) score on admission as well as 24 hours after the endovascular procedurals were collected. LOI was defined as a reduction of 3 points or less on the NIHSS at 24 hours compared with baseline. A 3-month functional outcome was assessed using the modified Rankin scale (mRS). Unfavorable outcome was prespecified as a score of more than 2 on the mRS. The onset-to-reperfusion time (ORT) was defined as time to mTICI 2b or 3 or end of procedure. Long ORT was defined as time to reperfusion beyond 6 hours. Poor reperfusion was defined as mTICI ≦2a. The pretreatment collateral circulation extent was graded as poor (grades 0-1) or good (grades 2-4). RESULTS: Among the 98 patients with AIS who were treated with ET, LOI was present in 48 (49%) subjects. Multivariate analysis indicated that poor collaterals (odds ratio [OR] 3.25; 95% confidence interval [CI]: 1.29-8.19; p = 0.012) and long ORT (OR 3.97, 95% CI: 1.66-9.54; p = 0.002) were independent predictors of LOI. LOI (OR 7.18, 95% CI: 2.39-21.61; p < 0.001) was independently associated with unfavorable outcome at 3 months. CONCLUSION: Among patients with AIS treated with ET, as an independent predictor of unfavorable outcome, LOI at 24 hours is associated with poor collaterals and long ORT.

Dynamic change of neutrophil to lymphocyte ratio and hemorrhagic transformation after thrombolysis in stroke.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been shown to predict short- and long-term outcomes in ischemic stroke patients. We sought to explore the temporal profile of the plasma NLR in stroke patients treated with intravenous thrombolysis (IVT) and its relationship with intracranial bleeding complications after thrombolysis. METHODS: A total of 189 ischemic stroke patients were prospectively enrolled. Blood samples for leukocyte, neutrophil, and lymphocyte counts were obtained at admission and at 3-6, 12-18, and 36-48 h after IVT. Head CT was performed on admission and repeated after 36-48 h, and a CT scan was done immediately in case of clinical worsening. Hemorrhagic events were categorized as symptomatic intracranial hemorrhage (sICH) and parenchymal hematomas (PH) according to previously published criteria. RESULTS: An increasing trend in the NLR was observed after stroke, and the NLR was higher in patients who developed PH or sICH at 3-6, 12-18, and 36-48 h after IVT (P < 0.01) than in those without PH or sICH. The optimal cutoff value for the serum NLR as an indicator for auxiliary diagnosis of PH and sICH was 10.59 at 12-18 h. Furthermore, the NLR obtained at 12-18-h post-treatment was independently associated with PH (adjusted odds ratio [OR] 1.14) and sICH (adjusted OR 1.14). In addition, patients with a NLR ≥10.59 had an 8.50-fold greater risk for PH (95 % confidence interval [CI] 2.69-26.89) and a 7.93-fold greater risk for sICH (95 % CI 2.25-27.99) than patients with a NLR <10.59. CONCLUSIONS: NLR is a dynamic variable, and its variation is associated with HT after thrombolysis in stroke patients.

Risk factors of severe hand, foot and mouth disease: a meta-analysis.

BACKGROUND: In recent years, outbreaks of hand, foot and mouth disease (HFMD) have increased, and more and more severe cases have appeared. We conducted a meta-analysis to generate large-scale evidence on the risk factors of severe HFMD. METHODS: PubMed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI), and Wanfang (Chinese) were searched to identify relevant articles. All analyses were performed using Stata 11.0. RESULTS: We conducted a meta-analysis of 19 separate studies. Duration of fever ≥ 3 days (odds ratio (OR) 10.09, 95% confidence interval (CI) 6.22-16.35), body temperature ≥ 37.5°C (OR 4.91, 95% CI 1.26-19.18), lethargy (OR 7.75, 95% CI 3.78-15.89), hyperglycemia (OR 2.77, 95% CI 2.06-3.71), vomiting (OR 8.83, 95% CI 1.05-74.57), increased neutrophil count (weighted mean difference (WMD) 0.61, 95% CI 0.52-0.70), enterovirus 71 (EV71) infection (OR 5.13, 95% CI 3.11- 8.46), young age (WMD - 0.44, 95% CI - 0.69 to -0.19), and home care (OR 1.65, 95% CI 1.26-2.17) were significantly related to the risk of severe HFMD. We also found that a confirmed diagnosis at first visit to hospital significantly decreased the risk of severe HFMD (OR 0.30, 95% CI 0.09-0.99). We did not find an association between oral rash (OR 1.07, 95% CI 0.82-1.39), increased leukocyte count (WMD 0.51, 95% CI - 0.05-1.06), male sex (OR 1.06, 95% CI 0.91-1.24), or living in a rural area (OR 1.39, 95% CI 0.95-2.02) and the risk of severe HFMD. CONCLUSIONS: Duration of fever ≥ 3 days, body temperature ≥ 37.5°C, lethargy, hyperglycemia, vomiting, increased neutrophil count, EV71 infection, and young age are risk factors for severe HFMD. A confirmed diagnosis at first visit to hospital can significantly decrease the risk of severe HFMD.

Effects of organic and inorganic selenium on selenium bioavailability, growth performance, antioxidant status and meat quality of a local beef cattle in China.

Selenium (Se) is an essential nutrient with multiple health benefits to humans and animals. Cattle generally require dietary Se supplementation to meet their daily requirements. The two main forms of dietary Se in cattle are organic Se and inorganic Se. Data comparing the health and productivity effects of organic Se and inorganic Se on cattle are still insufficient, and it is necessary to conduct more research to evaluate the bioavailability, nutritional value, deposition, and body functions of Se sources in different breeds and physiological stages of cattle raised in areas with different Se levels. The objectives of this study were to determine the effects of organic and inorganic sources of Se on plasma biochemical indices, Se bioavailability, deposition in body tissues and organs, growth performance, antioxidant capacity and meat quality of beef cattle raised in Se-deficient areas. Fifteen Chinese Xiangzhong Black beef cattle with an average weight of 254.5 ± 8.85 kg were assigned to three dietary groups. The three groups were fed the same basal ration and supplemented with either an inorganic [sodium selenite (SS)] or organic [selenomethionine (SM) or Se-enriched yeast (SY)] source of Se (0.1 mg/kg dry matter) for 60 days. At the end of the experiment, three cattle from each group were randomly selected and slaughtered, and samples were collected from tissues and organs for analysis. The results revealed that growth performance, slaughter performance, Se content of tissues and organs, meat quality characteristics including chemical composition, pH45min, pH24h, drip loss, and cooking losses did not differ (p > 0.05) due to supplementation of the different organic and inorganic sources of Se. SM and SY were more effective in increasing (p < 0.05) immunoglobulin M (IgM) concentrations in the blood and reducing (p < 0.05) malondialdehyde (MDA) content in the longissimus dorsi than SS. In conclusion, organic Se is more effective than inorganic Se in improving the immune and antioxidant capacity of Chinese Xiangzhong Black beef cattle.

A low-carbon high inulin diet improves intestinal mucosal barrier function and immunity against infectious diseases in goats.

Introduction: Abrupt weaning is a major stressful event, contributing to intestinal abnormalities and immune system dysfunction in weaned kids. Inulin is a prebiotic fiber with many positive functions, including promoting intestinal fermentation and enhancing host immunity in monogastric animals. However, the effects of a high-inulin, energy-rich diet on ruminal fermentation characteristics, methane emission, growth performance, and immune systems of weaned kids have not been investigated. Methods: A fully automated in vitro fermentation system was used to investigate ruminal fermentation characteristics and methane emission of a mixed substrate of inulin and fat powder (1.31: 1) in comparison with maize grain-based starter concentrate. During a 1-week adaptation and 4-week trial phase, 18 weaned kids (8.97 ± 0.19 kg) were randomly assigned to two groups, one with a conventional diet (83% maize grain; CON) and the other with a low-carbon, high-inulin diet (41.5% maize grain, 14.4% fat powder, 18.9% inulin; INU). Results: In the in vitro rumen fermentation experiment, the total gas production was not different (p > 0.05); however, a lower (p < 0.05) methane production was observed for INU as compared to CON. The average daily gain and the ratio of feed intake and growth performance of kids fed with INU were higher (p < 0.05) than those fed with CON. Serum concentrations of alanine transaminase (ALT) and lactate dehydrogenase (LDH) were lower (p < 0.05), whereas the concentration of high-density lipoprotein (HDL) and cholesterol (CHOL) were higher (p < 0.05) in kids fed with the INU diet as compared CON. Dietary inulin significantly increased (p < 0.05) the secretion of immunoglobulins (IgA, IgG, and IgM) and inflammatory cytokines (IFN-γ and IL-10) in ileum tissue. Although no differences (p > 0.05) were observed in mRNA expression of tight junction markers, the INU diet tended to increase (p = 0.09) gene expression of ribosomal protein S6 kinase beta-1 (P70S6K) in the mammalian target of rapamycin (mTOR) pathway of longissimus dorsi muscle. Conclusion: Our findings highlighted that a low-carbon high-inulin energy-rich diet could be used as a promising strategy to improve gut immunity and growth performance of weaned kids under abrupt weaning stress and reduce methane production.

Post-ASPECTS based on hyperdensity in NCCT immediately after thrombectomy is an ultra-early predictor of hemorrhagic transformation and prognosis.

Background and Purpose: Almost half of the patients exhibit futile recanalization after thrombectomy; however, the early postoperative predictors of futile recanalization remain unclear. We analyzed the relationship of post-thrombectomy ASPECTS (Post-ASPECTS) with 90-day prognosis and hemorrhagic transformation (HT). Methods: We collected data from patients with acute ischemic stroke (AIS) with anterior-circulation large vessel occlusion (ACLVO) who were treated via thrombectomy within 10 h in 3 hospitals. Successful endovascular recanalization was achieved (modified thrombolysis in cerebral ischemia [mTICI] 2b/3). Non-contrast computed tomography (NCCT) examination was performed immediately (within 1 h) after thrombectomy. Post-ASPECTS were scored based on the brain parenchymal hyperdensity in NCCT according to the ASPECTS scoring method. HT was defined according to the ECASS II classification criteria. Linear correlation, logistic regression, and receiver operating characteristic curve analyses were used to determine the influencing factors and best predictive value of 90-day prognosis, 90-day death, and HT. Results: A total of 231 patients were enrolled. The good prognosis rate, mortality rate, and HT rate were 57.1, 9.5, and 38.3%, respectively. The Post-ASPECTS affected poor prognosis, death, and HT. The best predictive value of Post-ASPECTS for poor prognosis, death, and HT was 7. The specificities of Post-ASPECTS for predicting HT, poor prognosis, and death were 87.6% (AUC, 0.811; P < 0.001), 87.1% (AUC, 0.768; P < 0.001), and 73.7% (AUC, 0.748; P < 0.001), with positive predictive values of 74.2, 75.7, and 21.4%, respectively. Conclusion: Post-ASPECTS predicted 90-day prognosis, death, and HT with high specificity and high positive predictive value in patients with AIS with ACLVO. Post-ASPECTS may be an ultra-early predictor of prognosis after thrombectomy.

[Discussion and prospect of infusion of NK cells in the treatment of SARS-CoV-2 infection].

This article aims at investigating the feasibility and potential of natural killer (NK) cells to treat corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Through retrospective analysis of existing anti-virus researches and clinical application results of NK cells, and based on the characteristics and properties of this cell, we designed a plan for NK cells to treat COVID-19. As an important part of the immune system, NK cells have clear anti-viral ability. In addition, it also plays the role in immune defense, immune surveillance and immune regulation. Many clinical applications have proved the safety and effectiveness of NK cell application. Currently COVID-19 is highly contagious and harmful to people, and easy to cause irreversible lung damage. Although quarantine can effectively prevent and control viral infections, there is no effective drug treatment available. To avoid further greater losses, it is tremendously necessary to investigate an effective treatment plan.

Feeding Fungal-Pretreated Corn Straw Improves Health and Meat Quality of Lambs Infected with Gastrointestinal Nematodes.

Infections with gastrointestinal nematodes (GIN) adversely affect meat color in lambs. Although white-rot fungi (WRF) pretreatment increases nutritional value and fiber digestion of corn straw for lambs, whether it can improve meat quality of lambs infected with GINs is unknown. The objective of this experiment was to study effects of feeding WRF-pretreated corn straw on the health and meat quality of lambs infected with GINs. Sixteen healthy Ujumqin lambs were orally drenched with 3rd-stage GINs larvae and randomly divided into two dietary treatments of control (CON) and WRF diets for 70 days of feeding. Results showed that feeding WRF-pretreated corn straw decreased L* and b* values (p < 0.05) and increased a* value (p < 0.01) of both longissimus thoracis et lumborum (LTL) and semimembranosus (SM) muscles of lambs infected with GINs. Feeding WRF-pretreatment corn straw decreased fecal egg count (p = 0.014) and increased packed cell volume (p = 0.013) of lambs from 28 d of feeding and increased plasma iron content (p = 0.008) of lambs from 56 d of the feeding. Feeding WRF-pretreatment corn straw decreased myosin heavy-chain (MyHC)-I (p = 0.032) and MyHC-IIα (p = 0.025) content in LTL muscle and MyHC-I (p = 0.022) and MyHC-IIß (p = 0.048) in SM muscle of lambs. In conclusion, although there were no significant changes in the content of most amino acids or increased intensity of better flavor compounds, meat quality and health of lambs infected with GINs was significantly improved by feeding WRF-pretreated corn straw due to increased PCV and meat color and tenderness.

High-potency white-rot fungal strains and duration of fermentation to optimize corn straw as ruminant feed.

Five white-rot fungi Pleurotus ostreatus, Lentinus edodes, Hericium erinaceus, Pleurotus eryngii and Flammulina filiformis were studied (solid-state incubation and in vitro gas production) to determine lignin degradation and optimal duration of fermentation of corn straw. All fungi significantly decreased lignin, with optimal reductions after 28 d. Although cellulose also decreased, L. edodes and P. eryngii minimized these losses. In intro dry matter digestibility, total volatile fatty acid concentration and total gas production of fermented corn straw decreased (P < 0.001) as fermentation was prolonged, with improved rumen fermentability for all fungal treatments except F. filiformis. Total gas production in L. edodes did not decrease but peaked on day 28, whereas F. filiformis reduced methane emission. In conclusion, fermentation of corn straw with P. eryngii or L. edodes for 28 d degraded lignin and improved nutritional value as ruminant feed.

Primary angioplasty and stenting may be superior to thrombectomy for acute atherosclerotic large-artery occlusion.

Objective The objective of this article is to compare the effectiveness of primary angioplasty and/or stenting with stent retriever thrombectomy in acute anterior large-vessel occlusion due to atherosclerotic disease. Methods Patients were retrospectively reviewed from the endovascular treatment for acute anterior circulation ischemic stroke registry. Patients with large-vessel occlusions due to atherosclerosis were selected. We evaluated modified Rankin Scale (mRS) score at 90 days, modified thrombolysis in cerebral infarction (mTICI) score immediately post-procedure, and symptomatic and asymptomatic intracranial hemorrhage within 72 hours. Results Of 302 patients with acute anterior circulation occlusion due to atherosclerotic disease, 269 were treated with stent retriever thrombectomy as first-line therapy and 33 with angioplasty and/or stenting. Patients who received primary angioplasty treatment showed favorable independent outcome at 90 days (69.7% (23/33) vs 47.6% (128/269), p = 0.02) and lower rate of asymptomatic intracranial hemorrhage (9.1% (3/23) vs 30.5% (82/269), p = 0.01). Recanalization immediately post procedure did not differ (78.8%% (26/33) vs 86.2% (232/269), p = 0.29). Primary angioplasty therapy (OR, 0.27; 95% confidence interval (CI): 0.08-0.90; p = 0.03) and small baseline infarct (OR 0.36: 0.16-0.82; p = 0.02) were protective factors against poor functional outcome, while old age (OR 1.04:1.01-1.07; p = 0.006), severe neurological deficits (OR 3.76: 2.00-7.07; p < 0.001), and high glucose (OR 1.11: 1.01-1.23; p = 0.03) were associated with poor prognosis. Conclusions Patients with acute anterior circulation large-vessel occlusion due to atherosclerosis may benefit from urgent angioplasty and/or stenting as first-line therapy. Randomized controlled trials are warranted.

proBDNF Accelerates Brain Amyloid-ß Deposition and Learning and Memory Impairment in APPswePS1dE9 Transgenic Mice.

BACKGROUND: Alzheimer's disease (AD) is pathologically known for the amyloid-ß (Aß) deposition, neurofibrillary tangles, and neuronal loss in the brain. The precursor of brain-derived neurotrophic factor (proBDNF) before proteolysis has opposing functions to its mature form in neuronal survival and neurite growth. However, the role of proBDNF in the pathogenesis of AD remains unclear. OBJECTIVE: To investigate the effects of proBDNF on neurons in vitro, and on learning and memory impairment and brain Aß production in a transgenic AD mouse model (APPswePS1dE9). METHODS: We here examined the effects of proBDNF on the viability (MTT assay) and neurite growth (morphologic measurement) of the primary neurons in vitro. After the intracerebroventricular injection of adeno-associated virus-proBDNF (AAV-proBDNF), we then investigated the learning and memory impairment (Morris water maze) and Aß deposition in the brains of the AD mice. RESULTS: The results showed that proBDNF could inhibit neuronal viability and neurite growth in vitro, enhance Aß levels, and accelerate its deposition in the brain, which was consistent with the learning and memory impairment of AD mice, likely dependent on the membrane receptor of p75NTR. CONCLUSIONS: Our findings suggest that proBDNF may exert a crucially negative effect during AD pathogenesis andprogression.

Prediction of favorable outcome by percent improvement in patients with acute ischemic stroke treated with endovascular stent thrombectomy.

Our objective was to investigate a method for assessing early improvement and its predictive value for 3-month functional outcome in patients treated with EST. A total of 97 consecutive AIS patients undergoing EST were prospectively collected and retrospective reviewed. Data on demographics, vascular risk factors, admission National Institutes of Health Stroke Scale (NIHSS) score, 24-h NIHSS score, reperfusion and collateral formation were collected. Percent improvement was defined as ([baseline NIHSS score-24-h NIHSS score]/baseline NIHSS score×100%), while absolute improvement was calculated by the difference between scores (baseline NIHSS score-24-h NIHSS score). A 3-month functional outcome was assessed using the modified Rankin Scale (mRS). Favorable outcome was defined as a mRS score of 0-2. Areas under the receiver-operating characteristic (ROC) curve (AUC) for percent improvement and absolute improvement in predicting favorable outcome was compared. Finally, we investigated the independent predictors of improvement at 24h after EST and its relationship with favorable outcome. Pairwise comparison of ROC curves revealed that percent improvement had larger AUC than absolute improvement (p=0.004). Rapid neurological improvement (RNI), defined as percent improvement ⩾30%, was a powerful predictor of favorable outcome (odds ratio [OR] 7.63, confidence interval [CI]: 2.65-21.96; p<0.001). Good collaterals (OR 2.86; 95% CI: 1.11-7.38; p=0.030) and short onset-to-reperfusion time (ORT) (OR 3.02, 95% CI: 1.17-7.80; p=0.022) were independent predictors of RNI. RNI predicted 3-month favorable outcome in AIS patients treated with EST. Good collaterals and short ORT are independent predictors of RNI.

Vascular endothelial growth factor expression and signaling in the lens.

PURPOSE: Previous studies have identified sequences encoding vascular endothelial growth factor (VEGF)-A and one of the VEGF receptors (VEGFR2, Flk-1, KDR) in lens fiber cells. The current study was undertaken to determine the distribution of VEGF-A protein in the lens, whether signaling through VEGF receptors occurs in lens cells, the pattern of VEGF-A expression during lens development, and the effect of hypoxia on VEGF-A expression. METHODS: VEGF-A and VEGFR2 were localized using immunocytochemistry. VEGF-A and VEGFR2 protein were identified and quantified by Western blot analysis. Activated (tyrosine phosphorylated) VEGFR2 was detected by immunoprecipitation with an anti-phosphotyrosine antibody followed by Western blot analysis with antibody to VEGFR2. Levels of VEGF-A mRNA were measured by quantitative PCR. Suturing the lids of adult mouse or rabbit eyes for 3 days was used to induce lens hypoxia. RESULTS: VEGFR2 sequences were present in adult human lens epithelial cells, and VEGF-A transcripts were detected in chicken embryo, adult human, and mouse lens epithelial cells. VEGF-A protein localized to the ends of mouse embryo lens fiber cells at developmental stages when the fetal vasculature was forming. At later stages, VEGF-A was distributed uniformly throughout the cytoplasm of cortical fiber cells. VEGFR2 was present in mouse lens epithelial and fiber cells and was tyrosine phosphorylated at all stages examined. VEGF-A protein was barely detectable in lens epithelial cells during the first postnatal week, but increased as the capillaries of the anterior pupillary membrane regressed. VEGF-A levels were highest in adult lenses. Suturing the eyelid caused an increase in VEGF-A mRNA and protein in lens epithelial and fiber cells. CONCLUSIONS: VEGF-A secreted by lens cells may stimulate the formation of the fetal vasculature, but regression of these vessels is not likely to be caused by a reduction in VEGF-A production by the lens. An active VEGF-A signaling system of unknown function appears to be active in the lens. It is likely that VEGF-A expression is regulated by tissue hypoxia at all stages of lens development.

Regulation of enhanced vacuolar H+-ATPase expression in macrophages.

The proton-translocating vacuolar ATPase (V-ATPase) acidifies the endocytic network of eukaryotic cells. Although all eukaryotic cell types require low to moderate levels of V-ATPase, some proton-secreting cells express amplified levels for use in specialized membrane domains. To characterize genetic elements required for this heightened expression, we studied transcription and stability of mRNA encoding the V-ATPase c subunit in a low expressing fibroblast cell line (NIH 3T3) and a high expressing macrophage cell line (RAW 264.7). Isolation of the promoter and mapping of the transcriptional start site indicated that the c subunit promoter is TATA-less and initiates transcription at a single site. Promoter activity was regulated through the same transcription factor binding sites in both cell types, which showed no discernible difference in rates of c subunit transcription. In contrast, c subunit transcripts showed markedly greater stability in RAW cells than in 3T3 cells, as did other constitutively expressed V-ATPase subunit transcripts. Only the B and 'a' subunits, which are expressed in multiple isoforms, were not regulated solely by mRNA stability. These results suggest that overall expression levels of the V-ATPase are set primarily by regulation of mRNA stability and that transcriptional mechanisms determine subunit composition in varying cell types.