[Peripheral blood KCNMA1 methylation level is associated with the occurrence and progression of lung cancer].

OBJECTIVE: To explore the association of KCNMA1 gene methylation levels in peripheral blood with lung cancer. METHODS: The methylation levels of 4 CpG sites in KCNMA1 gene were quantitatively detected in 285 patients with lung cancer, 186 age- and sex-matched patients with benign pulmonary nodules and 278 matched healthy control subjects using mass spectrometry (MALDI-TOF-MS). The association of KCNMA1 methylation levels with lung cancer was analyzed using logistic regression models adjusted for covariates. The KCNMA1 methylation levels in different subgroups of lung cancer patients were compared using Mann-Whitney U test. RESULTS: In subjects over 55 years and in female subjects, the highest quartile (Q4) vs the lowest quartile (Q1) of KCNMA1_CpG_5 methylation levels were significantly correlated with lung cancer (for subjects over 55 years: OR=2.60, 95% CI: 1.25-5.41, P=0.011; for female subjects: OR=2.09, 95% CI: 1.03?4.26, P=0.042). From Q2 to Q4 of KCNMA1_CpG_5 methylation levels, their correlation with lung cancer became gradually stronger (P=0.003 and 0.038, respectively). In male subjects, the OR of Q4 of KCNMA1_CpG_5 methylation levels was 0.35 in patients with lung cancer as compared with patients with benign nodules (95% CI: 0.16-0.79, P=0.012). KCNMA1_CpG_3 methylation level was significantly lower in invasive adenocarcinoma than in noninvasive adenocarcinoma (P=0.028), and that of KCNMA1_CpG_1 was significantly higher in patients with larger tumors (T2-4) than in those with smaller tumors (T1) (P=0.021). CONCLUSION: The change of peripheral blood KCNMA1 methylation level is correlated with the occurrence and development of lung cancer.

Potential biomarkers and lncRNA-mRNA regulatory networks in invasive growth hormone-secreting pituitary adenomas.

PURPOSE: Growth hormone-secreting pituitary adenomas (GH-PAs) are common subtypes of functional PAs. Invasive GH-PAs play a key role in restricting poor outcomes. The transcriptional changes in GH-PAs were evaluated. METHODS: In this study, the transcriptome analysis of six different GH-PA samples was performed. The functional roles, co-regulatory network, and chromosome location of differentially expressed (DE) genes in invasive GH-PAs were explored. RESULTS: Bioinformatic analysis revealed 101 DE mRNAs and 70 DE long non-coding RNAs (lncRNAs) between invasive and non-invasive GH-PAs. Functional enrichment analysis showed that epithelial cell differentiation and development pathways were suppressed in invasive GH-PAs, whereas the pathways of olfactory transduction, retinol metabolism, drug metabolism-cytochrome P450, and metabolism of xenobiotics by cytochrome P450 had an active trend. In the protein-protein interaction network, 11 main communities were characterized by cell- adhesion, -motility, and -cycle; transport process; phosphorus and hormone metabolic processes. The SGK1 gene was suggested to play a role in the invasiveness of GH-PAs. Furthermore, the up-regulated genes OR51B6, OR52E4, OR52E8, OR52E6, OR52N2, MAGEA6, MAGEC1, ST8SIA6-AS1, and the down-regulated genes GAD1-AS1 and SPINT1-AS1 were identified in the competing endogenous RNA network. The RT-qPCR results further supported the aberrant expression of those genes. Finally, the enrichment of DE genes in chromosome 11p15 and 12p13 regions were detected. CONCLUSION: Our findings provide a new perspective for studies evaluating the underlying mechanism of invasive GH-PAs.

[Initial exploration of discordance in public health standards in China].

Discordance, such as overlap, repetition and inconsistent, of standards is one of the major problems in current standardization affair in China. Therefore, improving the unity and authority of standards through reduction of overlap, repetition and inconsistency has become the main goal of deepening standardization reform in China. This paper summarizes the discordance in public health standards in China, analyzes the major reasons and provides specific strategic suggestions through case analysis of public health standards in the ways of comparisons of same kind standards of other deparments and standards in administration documents and guidelines or technical specifications of academic associations or societies.

[Discussion on implementation of public health standards adopted in centers for disease control and prevention].

As the most important phase in standardization activity, implementation saves as the essence. CDC in China are the major institutions undertaking disease control and prevention. Implementing the standards of public health provides technical basis for CDC to complete the task of disease control and prevention. In the study, spot conversation and questionnaire were used to investigate the implementation of standards on public health in CDC. Results showed that the staff of CDC got to know the standards through the Internet. The departments of CDC which conducted training and sent staff to attend training courses accounted for 50.00%(25/50) and 34.00%(17/50), respectively. State mandatory rule is still the main reason for relevant departments to implement the standards of the public health. Government promotion activities facilitate the implementation of Standards, and the degree of familiarity with Standards affects the implementation as well. The paper summarizes the existing problems, such as the lack of coordination between departments of public health at provincial level or below, lack of access to standards, and the need to strengthen the training of the standard implementation etc. It puts forward some suggestions to strengthen the implementation of public health Standards.

The impact of low-intensity extracorporeal shock wave therapy on testicular function in adult rats.

BACKGROUND: Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been introduced as a treatment for penile diseases. Its impact on testicular function during treatment remains unknown. OBJECTIVES: To clarify whether Li-ESWT impairs testicular function during the treatment of penile diseases by investigating the impact of Li-ESWT on testosterone synthesis and spermatogenesis in adult rats. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley rats were equally divided into the following three groups: control group, 1.6 BAR group, and 3.2 BAR group. Rats in the experimental groups were treated with Li-ESWT at different energy levels (300 shocks at 1.6 BAR or 3.2 BAR, 2 Hz frequency) three times a week for 3 weeks. The control group did not receive any treatment during the same period of time. One day after the last shock wave treatment, serum and testicular tissue testosterone concentrations were measured, and sperm quality was assayed. Histologic examination of the testes and quantitative real-time PCR were performed. RESULTS: Testosterone levels in both the serum and testicular tissue did not change after Li-ESWT exposure. The expression levels of steroidogenic enzymes (steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3ß-hydroxysteroid dehydrogenase (3ß-HSD)) were not impacted by Li-ESWT. The 3.2 BAR group showed a significantly lower sperm count and lower expression of synaptonemal complex protein 3 (SYCP3) in testicular tissue than the control group. No significant differences in sperm quality or SYCP3 expression were observed between the control group and the 1.6 BAR group. CONCLUSION: Li-ESWT exposure at 3.2 BAR inhibited spermatogenesis and decreased sperm quality, which indicated that male patients with a desire to preserve fertility should undergo low-energy Li-ESWT or other treatment modalities.

Effect of urinary trypsin inhibitor on inflammatory cytokines and organ function in patients with cardiopulmonary bypass.

OBJECTIVE: This research is to study the effect of urinary trypsin inhibitor (UTI) on inflammatory cytokines and organ function in patients with cardiopulmonary bypass. PATIENTS AND METHODS: From February 2015 to February 2016, 40 patients that had undergone cardiopulmonary bypass surgery in our hospital were selected and randomly divided into the observation group and the control group with 20 patients in each group. Patients in the control group were intravenously injected with 5000 U/kg normal saline during the operation and 5000 U/kg•d-1 at 1-3 days postoperatively, while the patients in the observation group received intravenous injection of the same amount of UTI at pre-operation (T0), post-anesthesia (T1), after aortic opening (T2), after cardiopulmonary bypass 4h (T3), 8h (T4), 24h (T5), 48h (T6), and 72h (T7). We detected tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and interleukin-8 (IL-8) levels in each group, and compared the pre and post-operative alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), direct bilirubin (DB) and creatinine level in the two groups of patients. RESULTS: At the time T3, T4, T5, T6, and T7, TNF-α, IL-1ß, IL-6, and IL-8 water in the observation group were significantly lower than those in the control group; the difference was statistically significant (p < 0.05). The 24 h postoperative ALT, AST, and TB of two groups were significantly higher than those pre-operatives (p < 0.05). The ALT and AST levels in the observation group were significantly lower than those in the control group after 24 h postoperative (p < 0.05). The 24 h postoperative TB DB of the two groups had not statistically significant differences (p > 0.05). At 24 h postoperative creatinine levels in the two groups were significantly lower than those before operation (p < 0.05), and there was no significant difference between the two groups (p > 0.05). In the observation group, the duration of ventilation and ICU hospitalization time were significantly lower than that in the control group, and the difference was statistically significant (p < 0.05). CONCLUSIONS: UTI can effectively regulate the inflammatory cytokines and provide protection for organ function during cardiopulmonary bypass surgery, which is conducive to promote the recovery of patients.

Synthesis of MoS2/g-C3N4 nanocomposites with enhanced visible-light photocatalytic activity for the removal of nitric oxide (NO).

Molybdenum disulfide and graphitic carbon nitride (MoS2-g-C3N4) nanocomposites with visible-light induced photocatalytic activity were successfully synthesized by a facile ultrasonic dispersion method. The crystalline structure and morphology of the MoS2-g-C3N4 nanocomposites were characterized by X-ray diffraction (XRD), transmission electron microcopy (TEM), high-resolution TEM (HRTEM) and scanning electron microscopy (SEM). The optical property of the as-prepared nanocomposites was studied by ultraviolet visible diffusion reflection (UV-vis) and photoluminescence(PL) spectrum. It could be observed from the TEM image that the MoS2 nanosheets and g-C3N4 nanoparticles were well combined together. Moreover, the photocatalytic activity of MoS2-g-C3N4 composites was evaluated by the removal of nitric oxide under visible light irradiation (>400nm). The experimental results demonstrated that the nanocomposites with the MoS2 content of 1.5 wt% exhibited optimal photocatalytic activity and the corresponding removal rate of NO achieved 51.67%, higher than that of pure g-C3N4 nanoparticles. A possible photocatalytic mechanism for the MoS2-g-C3N4 nanocomposites with enhanced photocatalytic activity could be ascribed to the hetero-structure of MoS2 and g-C3N4.

[Prognostic significance of mean amplitude of glycemic excursion in patients with severe burn].

OBJECTIVE: To retrospectively analyze the prognostic significance of mean amplitude of glycemic excursion (MAGE) in patients with severe burn. METHODS: A study involving 76 patients with severe burn admitted into Department of Burns of the Third People's Hospital of Wuxi City from January 2011 to August 2014, conforming to the inclusion criteria was conducted. Data of their demography, injury, and treatment were collected. Blood glucose level of patients was measured during the first 72 h after admission, and MAGE was calculated. (1) The patients were divided into survival group (n=46) and death group (n=30) according to the outcome within post injury day (PID) 90. The MAGE level of patients was compared between two groups. (2) The patients were divided into 3 groups by tertiles of MAGE within 72 h after admission, with 26 cases in low tertile group (MAGE<3.3 mmol/L), 27 cases in middle tertile group (with MAGE from 3.3 to 5.5 mmol/L), 23 cases in high tertile group (MAGE>5.5 mmol/L). The surviving curve was drawn using the Kaplan-Meier method to compare survival rates and surviving time of patients among the 3 groups within PID 90. Data were processed with t test, one-way analysis of variance, LSD test, chi-square test, and Fisher's exact test. The surviving curve was analyzed by the Log-rank test. Correlation was analyzed between demography, acute physiology and chronic health evaluation Ⅱ score, injury, treatment, sepsis, length of ICU stay, MAGE and death of patients using the univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve of MAGE was drawn to predict death for 76 patients. RESULTS: Within 72 h after admission, the MAGE of patients in death group was (6.0±1.4) mmol/L, which was significantly higher than that in survival group [(3.5±1.2) mmol/L, t=9.219, P=0.004]. The survival rates of patients in low tertile, middle tertile, and high tertile groups within PID 90 were respectively 88.5% (23/26), 59.3% (16/27), and 30.4% (7/23), with significant differences among 3 groups (χ(2)=18.073, P<0.001). The surviving time of patients in low tertile group [(83±21) d] was significantly longer than that of middle tertile group [(63±34) d, P<0.05]. The surviving time of patients was longer in low tertile and middle tertile groups than in high tertile group [(46±37) d, with P values below 0.05]. Total burn area, sepsis, blood purification, and MAGE were independent risk factors of death (with hazard ratio respectively 4.324, 1.591, 1.886, 2.047; 95% confidence interval respectively 2.978-6.119, 1.005-1.657, 1.614-2.408, 1.852-3.161; P<0.05 or P<0.01). The area under the ROC curve of MAGE for predicting death for 76 patients was 0.870 (with 95% confidence interval 0.786-0.966, P<0.001), and 4.7 mmol/L was chosen as the optimal threshold value, with sensitivity of 86.7% and specificity of 89.1%. CONCLUSIONS: The increase of MAGE in patients with severe burn is significantly associated with poor prognosis; controlling the glucose level fluctuation guided by measuring MAGE may be helpful in reducing mortality of patients.

Species-conserved reconfigurations of brain network topology induced by ketamine.

Species-conserved (intermediate) phenotypes that can be quantified and compared across species offer important advantages for translational research and drug discovery. Here, we investigate the utility of network science methods to assess the pharmacological alterations of the large-scale architecture of brain networks in rats and humans. In a double-blind, placebo-controlled, cross-over study in humans and a placebo-controlled two-group study in rats, we demonstrate that the application of ketamine leads to a topological reconfiguration of large-scale brain networks towards less-integrated and more-segregated information processing in both the species. As these alterations are opposed to those commonly observed in patients suffering from depression, they might indicate systems-level correlates of the antidepressant effect of ketamine.

Erectile dysfunction in patients with plaque psoriasis: the relation of depression and cardiovascular factors.

Psoriasis is a chronic inflammatory skin disease and seems to be associated with erectile dysfunction (ED). ED is a predictor of future cardiovascular disease. It is important to identify ED early and investigate cardiovascular problems in psoriasis patients. The sample consisted of 191 psoriasis patients and 191 healthy men. One hundred and one of 191 (52.9%) patients with psoriasis were indicative of ED, compared with 40.3% in control group, reflecting an age-adjusted odds ratio of 1.965 in favor of the psoriasis group. A univariate analysis in the psoriasis group indicated that age, hypertension, hyperlipidemia, diabetes mellitus and depressive symptoms were the risk factors for ED. The multivariate logistic regression model indicated that increasing age, hypertension, hyperlipidemia and depressive symptoms were independent risk factors for ED in psoriasis. The more severe depressive symptoms increased the risk of ED and especially moderate-severe ED. The diagnosis of ED may help prevent emotional and physical discomfort in men and aid in identifying reversible cardiovascular risk factors. Screening of ED may become a part of routine care in the management of psoriasis patients.

Surgical treatment of pacemaker induced left innominate vein occlusion using a spiral vein graft.

Superior vena cava syndrome due to transvenous pacing leads is an uncommon but potentially life-threatening complication. This case involves a 54-year-old man who developed left innominate vein occlusion due to a pacemaker lead. This complication induced a progressive swelling on the left side of his face, neck, arm, and upper chest. The left innominate vein occlusion was surgically treated using a composite spiral saphenous vein graft. Postoperatively, the patient has received anticoagulation therapy with warfarin to prevent thrombosis and, thereby, the long-term patency of the graft. He has undergone follow-up on a regular outpatient basis without showing any recurrence of clinical symptoms.

Intravesical immunotoxin as adjuvant therapy to prevent the recurrence of bladder cancer.

OBJECTIVE: To assess the intravesical application of immunotoxin as adjuvant therapy to prevent recurrence after tumor resection in bladder cancer patients. METHODS: An anti-human immunotoxin against bladder carcinoma, BDI-1-RT, was prepared and its in vitro targeting cytotoxicity estimated. The immunoreactivity of BDI-1-RT with human bladder cancer tissue of different grades and stages was detected by immunohistochemical analysis. After safety test, intravesical administration of BDI-1-RT was performed in 31 patients while mitomycin C (MMC) was used in 36 patients serving as a control group. The recurrence rates and side effects in both groups were recorded. In addition, the development of human anti-mouse antibodies (HAMA) was determined by ELISA, to assess the potential safety of this immunotoxin. RESULTS: In our study, BDI-1-RT had immunoreactivity with 81.6% of bladder transitional cell carcinomas. The immunoreactivity of BDI-1-RT correlated with tumor grade. High-grade carcinoma had stronger staining than low-grade (P < 0.05). There was no significant difference between the BDI-1-RT group (10%) and MMC group (19.3%) in recurrence rate (P > 0.05). Side effects, including systemic and local, were more frequent in the MMC group (11 of 36 patients versus 2 of 31, P < 0.05). HAMA was not detected in any of 7 patients. CONCLUSION: Immunotoxin may have considerable potential in the prophylaxis of bladder transition cell carcinoma.

Effect of major histocompatibility complex expression on murine intestinal graft survival.

BACKGROUND: Clinical intestinal transplantation has been plagued by frequent and severe graft rejection. It has been proposed that the major histocompatibility complex (MHC) antigens might play a critical role in this process owing to their extensive expression on enterocytes and mucosa-associated immune cells. METHODS: The present study examined the role of MHC antigens in intestinal graft rejection using MHC class I-deficient and MHC class II-deficient donors. RESULTS: Grafts with normal MHC expression were rejected by 9 days, whereas survival was prolonged to 14 days in the MHC class II-deficient grafts (P=NS) and to 20 days in the MHC I-deficient grafts (P<0.002). In all groups, early rejection was characterized by (1) increased crypt cell apoptosis, as detected by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique of in situ labeling; and (2) the increased expression of perforin and a CD8 phenotype in the graft-infiltrating cells. CONCLUSIONS: These data suggest that MHC antigens, CD8-positive T cells, and perforin-expressing cells contribute to intestinal graft rejection. Apoptosis of the progenitor epithelial crypt cells during early intestinal rejection may impair the gut's ability to regenerate and repair mucosal damage.

Differential regulation of expression of rat hippocampal muscarinic receptor subtypes following fimbria-fornix lesion.

Quantitative RNase protection assays were performed to determine the levels of muscarinic receptor subtype (m1-m5) mRNAs in rat hippocampi. Results showed that the m1, m3, and m4 subtype mRNAs were expressed at relatively high levels, but the levels of the m2 and m5 subtype were very low. Three weeks following aspiration lesions of the fimbria-fornix to produce cholinergic denervation of the hippocampus, non-M1 receptors (non-pirenzepine displaceable [3H]quinuclindinyl benzilate binding sites) in the hippocampus were increased significantly, which correlated with increases in the levels of hippocampal m3 and m4 receptor mRNAs (m3: +24% and m4: +41%). These findings indicate that multiple muscarinic receptor subtypes are expressed in the hippocampus with the m3 and m4 subtypes predominantly postsynaptic to the septohippocampal cholinergic terminals.

Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells.

The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor beta superfamily, the bone morphogenetic proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic subventricular zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny.

Aggregation of the Fc epsilon RI in mast cells induces the synthesis of Fos-interacting protein and increases its DNA binding-activity: the dependence on protein kinase C-beta.

The ability of c-Fos to dimerize with various proteins creates transcription complexes which can exert their regulatory function on a variety of genes. One of the transcription factors that binds to c-Fos is the newly discovered Fos-interacting protein (FIP). In this report we present evidence for the regulation of the synthesis of FIP by a physiological stimulus. We found that the aggregation of the mast cell high affinity receptor for IgE (Fc epsilon RI) induced the synthesis of FIP and increased its DNA binding activity. Moreover, down-regulation of the isoenzyme protein kinase C-beta (PKC-beta) by a specific antisense phosphorothioate oligonucleotide resulted in profound inhibition of FIP-Fos DNA binding activity. Thus, aggregation of the Fc epsilon RI on mast cells elicits a PKC-beta dependent signaling pathway which regulates FIP-Fos DNA binding activity.

Cytokines regulate the cellular phenotype of developing neural lineage species.

The patterns and mechanisms of action of inductive signals that orchestrate neural lineage commitment and differentiation in the mammalian brain are incompletely understood. To examine these developmental issues, we have utilized several culture systems including conditionally immortalized cell lines, subventricular zone progenitor cells and primary neuronal cultures. A neural stem and progenitor cell line (MK31) was established from murine embryonic hippocampus by retroviral transduction of temperature-sensitive alleles of the simian virus 40 large tumor antigen. At the non-permissive temperature for antigen expression (39 degrees C) in serum-free media, the neural stem cells give rise to a series of increasingly mature neuronal progenitor and differentiated cellular forms under the influence of a subset of hematolymphopoietic cytokines (interleukins 5, 7, 9 and 11), when individually co-applied with transforming growth factor alpha, after pretreatment with basic fibroblast growth factor. These cellular forms elaborated a series of progressively more mature neurofilament proteins, a sequential pattern of ligand-gated channels, and inward currents and generation of action potentials with mature physiological properties. Because the factors regulating the development of central nervous system astrocytes have been so difficult to define, we have chosen to focus, in this manuscript, on the elaboration of this cell type. At 39 degrees C, application of a subfamily of bone morphogenetic proteins of the transforming growth factor beta superfamily of growth factors sanctioned the selective expression of astrocytic progenitor cells and mature astrocytes, as defined by sequential elaboration of the Yb subunit of glutathione-S-transferase and glial fibrillary acidic protein. These lineage-specific cytokine inductive relationships were verified using subventricular zone neural progenitor cells generated by the application of epidermal growth factor, alone or in combination with basic fibroblast growth factor, to dissociated cellular cultures derived from early embryonic murine brain, a normal non-transformed developmental population. Finally, application of a different series of cytokines from five distinct factor classes (basic fibroblast growth factor, platelet-derived growth factor-AA, insulin-like growth factor 1, neurotrophin 3 and representative gp130 receptor subunit-related ligands) caused the elaboration of oligodendroglial progenitor species and post-mitotic oligodendrocytes, defined by progressive morphological maturation and the expression of increasingly advanced oligodendroglial and oligodendrocyte lineage markers. In addition, seven different gp130-associated neuropoietic (ciliary neurotrophic factor, leukemia inhibitory factor, oncostatin-M) and hematopoietic (interleukins 6, 11, 12, granulocyte-colony stimulating factor) cytokines exhibited differential trophic effects on oligodendroglial lineage maturation and factor class interactions.(ABSTRACT TRUNCATED AT 400 WORDS)

mRNAs encoding muscarinic and substance P receptors in cultured sympathetic neurons are differentially regulated by LIF or CNTF.

Leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) have previously been shown to regulate neuronal choice of neurotransmitter. In this present study, these factors were shown to specifically and differentially regulate levels of both muscarinic (subtypes m1, m2, m3, m4, and m5) and substance P receptor (SPR) mRNAs in sympathetic neurons of the rat superior cervical ganglion (SCG) using solution hybridization/RNase protection analysis. In vivo, neonatal rat SCG expressed predominantly m2 (10.31 +/- 0.43 pg mRNA/micrograms total RNA) and some m1 (1.54 +/- 0.84 pg/microgram) muscarinic receptor mRNA, which increased developmentally to adult levels (m2 mRNA levels being 60% higher than those in neonates). By contrast, m3, m4, and m5 subtype mRNAs were much less abundant at all time points measured. A similar developmental regulation was found in dissociated SCG neurons in vitro. After 16 days in culture, m2 mRNA increased 334% to 15.76 +/- 0.68 pg/microgram, while m1 mRNA changed little (2.03 +/- 1.00 pg/microgram). However, LIF or CNTF treatment (5 ng/ml, 14 days) in sister cultures completely blocked this developmental increase. Further, LIF treatment blocked the normal muscarinic receptor-mediated increase in intracellular calcium (fura-2 imaging), indicating a functional change in receptor phenotype. By contrast, levels of SPR mRNA, which were low in untreated cultures (0.037 +/- 0.025 pg SPR mRNA/microgram total RNA), were elevated by LIF or CNTF treatment, to 0.866 +/- 0.034 pg/microgram and 0.662 +/- 0.148 pg/microgram, respectively. These observations indicate that muscarinic and SPR receptor expression are differentially regulated by the same factors in SCG neurons and that neuronal choice of receptor phenotype may be, at least in part, specifically regulated by cytokines/growth factors in the cellular milieu.