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PubMed1998

Posthatching myofiber development in the M. pectoralis of White Pekin Ducks.

BACKGROUND: A posthatching transformation of fast-twitch oxidative-glycolytic (FTO) to fast-twitch glycolytic (FTG) fibers in the breast muscle in domestic chickens and turkeys is well documented. There is, however, no information on the situation in Anseriformes having a M. pectoralis with a mixed fiber composition in adults. Differences in the growth of the different fiber types were reported for some muscles in ducks as well as in other birds. They are examined in the main flight muscle using growth curve analysis, until now mostly applied to the analysis of overall growth. METHODS: Biopsies were taken longitudinally from the M. pectoralis, Pars thoracica, of 40 White Pekin Ducks at 11 different ages from hatching through day 146. The samples were processed for a combination of nicotinamide adenine dinucleotide tetrazolium reductase and myosin adenosine triphosphatase after acid preincubation at pH 4.1. Mean fiber diameter was determined for the different fiber types in relation to age. The Janoschek growth curve was fitted to these values. RESULTS: FTG fibers were first detected at 20 days of age. Thereafter, the fiber composition hardly changed. When distinguishable by enzyme histochemistry, FTG fibers were already larger in diameter than FTO. There were only gradual differences in the growth pattern. FTG fibers, however, showed much higher absolute, percentage, and relative growth rates. The radial growth of myofibers is slow when compared to other one-dimensional measurements. CONCLUSIONS: Fiber transformation seems to take place within a short age period. However, further studies are necessary to discriminate effects resulting from sample depth. FTG fibers are presumably recruited from those FTO fibers that show higher growth rates. Growth curve analysis, more frequently used in gross morphological studies, provides an analytical tool for evaluating growth processes of cells and tissues as well. Fiber size differences are mainly due to a higher growth rate in FTG fibers, whereas the growth patterns show only minor differences.

Adenosine Triphosphatases↗

PubMed2005

Investigation of the electric field in TiO2/FTO junctions used in dye-sensitized solar cells by photocurrent transients.

We have investigated the electrostatic potential distribution in compact and nanoporous TiO2 films, deposited on conducting F-doped SnO2 substrate (FTO), which are used in dye-sensitized solar cells. The TiO2 films were immersed into aqueous electrolyte and excited from the FTO side by light pulses of a N2 laser while the current response was measured as a function of time. The measurements were carried out as a function of the pH value of the electrolyte and at different electrostatic potentials. For compact TiO2 films, the sign of the transient current at short response times changed when the applied electrostatic potential or the pH value was decreased. This was not observed for mesoporous TiO2 films directly deposited onto the FTO substrate without a compact TiO2 layer. We interpret the results in terms of a macroscopic electric field across the compact layer which is changed by the applied potential or the pH of the electrolyte. In contrast, measurements on mesoporous TiO2 films indicate that the contact region is mainly field-free, and we explain our results by a very sharp electrostatic potential drop within the first layer of particles at the TiO2/FTO interface.

Journal Article↗

PubMed2005

Illumination intensity dependence of the photovoltage in nanostructured TiO2 dye-sensitized solar cells.

The open-circuit voltage (V(oc)) dependence on the illumination intensity (phi0) under steady-state conditions in both bare and coated (blocked) nanostructured TiO2 dye-sensitized solar cells (DSSCs) is analyzed. This analysis is based on a recently reported model [Bisquert, J.; Zaban, A.; Salvador, P. J. Phys. Chem. B 2002, 106, 8774] which describes the rate of interfacial electron transfer from the conduction band of TiO2 to acceptor electrolyte levels (recombination). The model involves two possible mechanisms: (1) direct, isoenergetic electron injection from the conduction band and (2) a two-step process involving inelastic electron trapping by band-gap surface states and subsequent isoenergetic transfer of trapped electrons to electrolyte levels. By considering the variation of V(oc) over a wide range of illumination intensities (10(10) < phi0 < 10(16) cm(-2) s(-1)), three major regions with different values of dV(oc)/d phi0 can be distinguished and interpreted. At the lower illumination intensities, recombination mainly involves localized band-gap, deep traps at about 0.6 eV below the conduction band edge; at intermediate photon fluxes, recombination is apparently controlled by a tail of shallow traps, while, for high enough phi0 values, conduction band states control the recombination process. The high phi0 region is characterized by a slope of dV(oc)/d log phi0 congruent with 60 mV, which indicates a recombination of first order in the free electron concentration. The study, which was extended to different solar cells, shows that the energy of the deep traps seems to be an intrinsic property of the nanostructured TiO2 material, while their concentration and also the density ([symbol: see text]t approximately 10(18)-10(19) cm(-3)) and distribution of shallow traps, which strongly affects the shape of the V(oc) vs phi0 curves, change from sample to sample and are quite sensitive to the electrode preparation. The influence of the back-reaction of electrons from the fluorine-doped tin oxide (FTO) conducting glass substrate with electrolyte tri-iodide ions on the V(oc) vs phi0 dependence characteristic of the DSSC is analyzed. It is concluded that this back-reaction route can be neglected, even at low light intensities, when its rate (exchange current density, j0), which can vary over 4 orders of magnitude depending on the type of FTO used, is low enough (j0 < or = 10(-8)A cm(-2)). The comparison of V(oc) vs phi0 measurements corresponding to different DSSCs with and without blocking of the FTO-electrolyte contact supports this conclusion.

Journal Article↗

PubMed2001

Transforming growth factor-beta1-induced Smad signaling, cell-cycle arrest and apoptosis in hepatoma cells.

Transforming growth factor-beta1 (TGFbeta) is involved in the regulation of liver cell proliferation and apoptosis, and escape of hepatoma cells from the growth restraining signals of TGFbeta has been suggested to contribute to tumor development. TGFbeta modulates gene transcription by receptor-mediated activation of Smad proteins which act as transcription factors. TGFbeta-mediated primary signaling responses as well as effects on the cell cycle and apoptosis were investigated in the human hepatoblastoma line HepG2, the rat hepatoma line FTO-2B and the mouse hepatoma line 55.1c. Activation of a Smad (Sma and Mad homolog) response-element-driven luciferase reporter by TGFbeta was very similar in all three cell lines, indicating functionality of the primary TGFbeta signaling pathway. Moreover, TGFbeta-inducible early gene was transiently activated by TGFbeta in all cell lines as shown by RT-PCR. HepG2 cells, however, were completely resistant to TGFbeta-induced growth arrest and apoptosis and 55.1c cells were only slightly susceptible to TGFbeta-induced apoptosis. By contrast, treatment of FTO-2B cells with TGFbeta led to a partial G0/G1 arrest and a strong induction of apoptosis. TGFbeta-induced apoptosis of FTO-2B cells was inhibited by dexamethasone, insulin, phenobarbital and dieldrin. Of these agents, only insulin led to a significant reduction of TGFbeta-stimulated Smad-reporter activity, suggesting that the other compounds interfere with TGFbeta-induced apoptosis downstream of Smad-mediated primary transcriptional responses at a level that may be constitutively altered in apoptosis-resistant hepatoma cell lines.

Apoptosis↗

PubMed1998

Phenotypic characterization of rat hepatoma cell lines and lineage-specific regulation of gene expression by differentiation agents.

Hepatoma cell lines can be characterized by their expression of hepatocyte- and biliary-specific genes and by their response to differentiating agents in a lineage-dependent manner. These characteristics can be used to map the maturational lineage position of the cell lines. Tissue-specific gene expression and regulation by heparin, dimethylsulfoxide (DMSO), and sodium butyrate (SB) were examined in three rat hepatoma cell lines and two rat liver epithelial cell lines. Based on antigenic profiles and gene expression in serum-supplemented medium, the hepatoma cell lines could be organized in distinct categories of hepatic differentiation. All three hepatomas expressed the following five genes: gamma-glutamyl transpeptidase (GGT), glutathione-S-transferase pi (Yp), glutamine synthetase, and alpha 5 and beta 1 integrin. Cell line H4AzC2 also expressed alpha-fetoprotein (AFP), albumin. IGF II receptor, and the biliary/oval cell antigens OC.2 and OC.3, a phenotype characteristic of fetal hepatocytes. FTO-2B cells lacked AFP, OC.2, and OC.3 but expressed albumin and IGF II receptor in addition to the five commonly expressed genes, consistent with a more hepatocyte-like phenotype. Cell line H5D-7 expressed neither albumin nor the IGF II receptor, but did express OC.2, OC.3, and alpha 3 integrin in addition to the five commonly expressed genes, characteristic of biliary epithelial cells. Regulation of gene expression by heparin, DMSO, and SB was examined in cells cultured in hormonally defined medium. The patterns of regulation of AFP, albumin, GGT, and Yp were dependent upon the state of differentiation of the cell. FTO-2B cells regulated genes in a manner similar to that of E16 fetal hepatocytes, H4AzC2 regulated genes characteristic of both hepatocytic and biliary lineages, and H5D.7 regulated only biliary genes. Suppression of GGT by DMSO was uniformly observed. The three cell lines expressed equal amounts of HNF-4, but FTO-2B cells expressed more HNF-3 beta and less HNF-3 alpha, while the reverse was true of H4AzC2 and H5D.7 cells.

Animals↗

PubMed1994

Glucokinase expression in rat hepatoma cells induces glucose uptake and is rate limiting in glucose utilization.

In contrast to hepatocytes, hepatoma cells lack glucokinase activity and show increased aerobic glycolysis. FTO-2B and H4IIE rat hepatoma cell lines were obtained in which the rat glucokinase gene was expressed (FTOGK and H4GK). These lines were generated by infection of the hepatoma cells with a retroviral vector carrying the phosphoenolpyruvate carboxykinase (PEPCK)-glucokinase chimeric gene. Both the FTOGK and H4GK cells expressed the chimeric gene in a regulated manner, like the endogenous PEPCK gene. Glucokinase activity was detected in both FTOGK and H4GK. These cells lines showed a marked increase in glucose uptake with 18.5 mM glucose in the incubation medium. FTOGK and H4GK showed an increase in the content of glucose 6-phosphate, and were able to accumulate high levels of glycogen, in contrast to FTO-2B cells, which were unable to store the polysaccharide. In addition, cells expressing glucokinase showed high concentration of fructose 2,6-bisphosphate and substantial lactate production, which was related to the glucose concentration in the medium and the time of incubation. These results suggest that glucose phosphorylation is rate limiting for glucose uptake and utilization in FTO-2B and H4IIE cells.

Animals↗

PubMed1986

Regulation of gene expression in rat hepatocytes and hepatoma cells by insulin: quantitation of messenger ribonucleic acid's coding for tyrosine aminotransferase, tryptophan oxygenase, and phosphoenolpyruvate carboxykinase.

The effect of insulin on the abundance of mRNAs coding for tyrosine aminotransferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TO; EC 1.13.1.12), and P-enolpyruvate carboxykinase(GTP) (PEPCK; EC 4.1.1.32) was examined in primary cultures of adult rat hepatocytes and in FTO-2B rat hepatoma cells by Northern blot analysis using RNA probes made from SP6-cDNAs. Insulin (10(-11)-10(-7) M), which has been reported to induce TAT and decrease the activity of TO, did not change the levels of TAT mRNA and TO mRNA in hepatocytes regardless of the presence of other inducers. In the same cells, dexamethasone increased TAT mRNA up to 19-fold and TO mRNA up to 15-fold, and 8pClPhS-cAMP (CPT-cAMP) raised the level of TAT mRNA up to 36-fold. The abundance of TO mRNA was not altered by CPT-cAMP. In contrast to TAT mRNA and TO mRNA, the level of PEPCK mRNA was dramatically decreased by insulin in the same hepatocytes. The sensitivity to this inhibitory effect of insulin was enhanced by dexamethasone and reduced by CPT-cAMP. FTO-2B hepatoma cells, which do not express detectable levels of TO mRNA, showed responses similar to those of hepatocytes, except that insulin caused a moderate reduction in TAT mRNA, but only in the presence of CPT-cAMP. The PEPCK mRNA in FTO-2B cells was suppressed by insulin in a manner closely resembling the effects in hepatocytes in the present study and in H4IIE hepatoma cells previously reported.

Animals↗

PubMed1990

Vanadate inhibits expression of the gene for phosphoenolpyruvate carboxykinase (GTP) in rat hepatoma cells.

Vanadate, at concentrations between 0.5 and 2 mM, rapidly decreased the basal level of P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) mRNA and blocked the dibutyryl cyclic AMP (Bt2cAMP)-induced increase in enzyme mRNA in both FTO-2B and H4IIE rat hepatoma cells. The concentration of vanadate necessary to inhibit the expression of this gene was similar to that required for the vanadate-mediated activation of the insulin receptor tyrosine kinase. To determine whether vanadate could inhibit PEPCK gene transcription, a series of chimeric genes containing several deletions in the P-enolypyruvate carboxykinase promoter between -550 and -68 was linked to the structural genes for either amino-3-glycosyl phosphotransferase (neo) or chloramphenicol acetyltransferase and introduced into hepatoma cells using three methods: (a) infection with a Moloney murine leukemia virus-based retrovirus, (b) transfection and stable selection for neo expression, or (c) transient expression of chloroamphenicol acetyltransferase. In FTO-2B hepatoma cells infected with retrovirus, vanadate rapidly (within 1 h) inhibited transcription of the PEPCK-neo gene and blocked induction of gene expression caused by the addition of either Bt2cAMP or dexamethasone to the cells. Vanadate was not a general transcription inhibitor since, it like insulin, stimulated the expression of the c-fos gene. Also, the inhibitory effect of vanadate was rapidly reversible in FTO-2B cells since PEPCK gene expression could be stimulated by Bt2cAMP and dexamethasone after removal of vanadate. A series of 5' deletions in the P-enolpyruvate carboxykinase promoter (-550 to +73) was ligated to the structural gene for neo and stably transfected into hepatoma cells. Sequences responsive to vanadate were detected between -109 and -68. This result was confirmed using H4IIE hepatoma cells transiently expressing the PEPCK-CAT gene. The most likely target for vanadate in that region of the P-enolpyruvate carboxykinase promoter is cAMP regulatory element 1 which maps from -91 to -84. A comparison of the inhibitory effects of insulin and vanadate in this system indicated a major difference in the site of action of these two compounds on PEPCK gene transcription.

Animals↗

PubMed1983

[Development of fiber type composition and fiber diameter in the longissimus muscle of the domestic pig (Sus scrofa domesticus)].

The development of fiber types composition and fiber diameter in porcine longissimus muscle from birth to the age of 5 years was examined by means of cross-sectional study. The fiber types were classified in the following manner: FTG = fast-twitch-glycolytic, FTO = fast-twitch-oxidative and STO = slow-twitch-oxidative. The percentage on the oxidative fibers decrease from 60.8% on the 1st d to 39.1% on the 100th d of life. On the 1800th d only 26.5% oxidative fibers are present. The average diameters of fiber types increase during the whole examination period, especially to the 100th d of life. The initial gradation of fiber diameter FTG = 63 micron, FTO = 62 micron, STO = 56 micron converts during growth into STO = 112 micron, FTO = 108 micron, FTG = 104 micron. A common representation of muscle fiber diameter growth curve and rump length growth curve demonstrates different growth modes of muscle and skeleton.

Age Factors↗

PubMed2025

N6-methyladenosine RNA base modification regulates NKG2D-dependent and cytotoxic genes expression in natural killer cells.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed cancer in women. N6-methyladenosine (m6A) is the most prevalent internal modification in mammalian mRNAs and plays a crucial role in various biological processes. However, its function in Natural killer (NK) cells in BC remains unclear. NK cells are essential for cancer immunosurveillance. This study aims to assess m6A levels in transcripts involved in the NKG2D cytotoxicity signaling pathway in NK cells of BC patients compared to controls and find out its impact on mRNA levels. Additionally, it evaluates how deliberately altering m6A levels in NK cells affects mRNA and protein expression of NKG2D pathway genes and NK cell functionality. METHODS: m6A methylation in transcripts of NKG2D-pathway-related genes in BC patients and controls was determined using methylated RNA immunoprecipitation-reverse transcription-PCR (MERIP-RT-PCR). To deliberately alter m6A levels in primary cultured human NK cells, the m6A demethylases, FTO and ALKBH5, were knocked out using the CRISPR-CAS9 system, and FTO was inhibited using Meclofenamic acid (MA). The impact of m6A alteration on corresponding mRNA and protein levels was assessed using RT-qPCR and Western blot analysis or flow cytometry, respectively. Additionally, NK cell functionality was evaluated through degranulation and 51Cr release cytotoxicity assays. RESULTS: Transcripts of NKG2D, an activating receptor that detects stressed non-self tumour cells, had significantly higher m6A levels in the 3' untranslated region (3'UTR) accompanied by a marked reduction in their corresponding mRNA levels in BC patients compared to controls. Conversely, transcripts of ERK2 and PRF1 exhibited significantly lower m6A levels escorted with higher mRNA expression in BC patients relative to controls. The mRNA levels of PI3K, PAK1 and GZMH were also significantly elevated in BC patients. Furthermore, artificially increasing transcripts' m6A levels via MA in cultured primary NK cells reduced mRNA levels of NKG2D pathway genes and death receptor ligands but did not affect protein expression or NK cell functionality. CONCLUSION: Transcripts with higher m6A levels in the 3'UTR region were less abundant, and vice versa. However, changes in mRNA levels of the target genes didn't impact their corresponding protein levels or NK cell functionality.

Humans↗

PubMed2025

Genetic Determinants of Leisure-Time Physical Activity in the Taiwanese Population: A Genome-Wide Association Study.

BACKGROUND: Physical inactivity contributes to systemic disease burden and premature mortality worldwide. Leisure-time physical activity (LTPA) improves health outcomes; however, its genetic determinants, particularly in Asian populations, remain unclear. This study aimed to identify genetic loci associated with LTPA in the Taiwanese population. METHODS: We conducted genome-wide association studies in 122,258 Taiwan Biobank participants. LTPA was assessed both as a binary trait (regular exerciser vs non-exerciser) and an ordinal trait (categorized by MET-hours per week into low, moderate, and high physical activity levels). Logistic and ordinal logistic regression models were used under an additive genetic model, adjusting for age, age 2 , sex, body mass index, smoking, and the first 10 genetic principal components. Candidate nonsynonymous mutations were further examined in 1494 whole-genome sequenced participants. RESULTS: Binary trait genome-wide association studies identified genome-wide significant (GWS) loci at ATXN2 (12q24.12), FTO (16q12.2), and NOTCH4 (6p21.32), with associations for FTO and NOTCH4 only observed in body mass index (BMI)-adjusted models. Ordinal trait analysis (<10, 10-<20, ≥20 MET·h·wk -1 ) identified a single GWS locus at BRAP (12q24.12). Fine-mapping of 12q24.12 revealed multiple GWS single-nucleotide polymorphisms (SNPs) in strong linkage disequilibrium with lead variants; these signals largely disappeared after conditional analysis, consistent with a single underlying association. Whole-genome sequencing and linkage disequilibrium analysis identified three GWS nonsynonymous mutations, with ALDH2 rs671 emerging as the most likely causal variant. CONCLUSIONS: ATXN2-ALDH2 region on chromosome 12q24.12 was identified as a key locus for LTPA in Taiwanese individuals. These findings enhance our understanding of the genetic basis of physical activity and may inform future precision medicine and public health strategies.

Adult↗

PubMed2026

Maternal immune activation perturbs the brain epitranscriptome.

Maternal immune activation (MIA) results in abnormal fetal neurodevelopment and an increased risk of neurodevelopmental disorders. Altered RNA translation has been implicated in the pathophysiology of MIA-associated neurodevelopmental deficits, but more precise mechanisms underlying disruption in RNA metabolism are lacking. Here, we characterize key components of the RNA epitranscriptomic machinery, which refers to the set of reversible chemical modifications on RNA molecules that influence RNA function, including translation, stability, splicing, and localization. Using spatial transcriptomics, we define cell type- and brain region-specific distribution of epitranscriptome regulators in the developing mouse brain. We also use direct RNA sequencing to define how MIA changes the brain epitranscriptome landscape. We identify the demethylase FTO as being notably perturbed in the context of MIA. Using pharmacological and genetic approaches, we target FTO to ameliorate behavioral phenotypes in MIA offspring. In total, this work expands upon mechanisms of translational misregulation in MIA and identifies new targets for therapeutic manipulation.

Animals↗

PubMed1993

Gi alpha 2 mediates the inhibitory regulation of adenylylcyclase in vivo: analysis in transgenic mice with Gi alpha 2 suppressed by inducible antisense RNA.

The role of the GTP-binding regulatory protein (G-protein) Gi alpha 2 in vivo was explored using transgenic mice in which the alpha-subunit of Gi alpha 2 was suppressed by antisense RNA. Rat hepatoma FTO-2B cells provide an ideal test system for constructs employing the expression vector pPCK-AS, designed to express antisense RNA at birth under the control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter. Cells transfected with the expression vector containing a sequence antisense to Gi alpha 2 (pPCK-ASGi alpha 2) displayed expression of RNA antisense to Gi alpha 2 that, like transcription of the PEPCK gene, was inducible by cyclic AMP. Expression of RNA antisense to Gi alpha 2 and suppression of the expression of Gi alpha 2, but not Gsa and Gi alpha 3, was observed in the transfected FTO-2B cells. BDF1 mice carrying the transgene displayed suppression of Gi alpha 2 in liver and fat, two targets for tissue-specific expression of the PEPCK gene. The loss of Gi alpha 2 in white adipocytes of transgenic mice resulted in 3.1-fold elevation of basal cyclic AMP accumulation. Cyclic AMP accumulation in response to stimulation by epinephrine (10 microM) was normal in adipocytes of transgenic mice, demonstrating no alteration in the stimulatory adenylylcyclase capacity in the Gi alpha 2-deficient cells. The inhibitory adenylylcyclase pathway, in sharp contrast, was severely blunted in response to challenge by the inhibitory A1-purinergic agonist, (-)R-N6-phenylisopropyladenosine. These studies illuminate a critical role of Gi alpha 2 in the inhibitory adenylylcyclase signaling pathway in vivo.

Adenylyl Cyclases↗

PubMed1995

Insulin-like growth factor II regulation of gene expression in rat and human hepatomas.

Insulin-like growth factor II (IGF II) regulated tissue-specific gene expression in hepatoma cell lines, but had no effect on expression of tissue-specific genes in primary cultures of E14 and newborn rat liver cells depleted of erythroid cells. No change was observed in these primary cultures with respect to alpha-fetoprotein (alpha-FP), albumin, cytokeratin 19 (CK19), gamma-glutamyltranspeptidase (GGT), and IGF II receptors. Two well-differentiated hepatoma, HepG2 and FTO-2B, and a poorly differentiated hepatoma, H4AzC2, did not show increased proliferation in the presence of IGF II, yet showed gene expression changes in response to IGF II. In HepG2 cells, IGF II increased albumin mRNA levels and resulted in a shift from clusters of cells positive to 100% of the cells expressing immunohistochemically detectable albumin. The transcription factor HNF-3 beta mRNA and protein levels of the bile duct markers, CK19 and GGT, were also increased in the presence of IGF II. Other genes tested were not affected, including alpha-1-antitrypsin, and two liver-specific transcription factors, HNF-4 and HNF-3 alpha. In FTO-2B cells, IGF II increased the expression of albumin, CK19, and GGT, without accompanying changes in albumin and GGT mRNAs. In H4A7C2 cells, IGF II reduced CK19 and OC.3 protein levels and GGT, transferrin, and HNF-3 beta mRNAs. The effects of IGF II on H4AZC2 cells were not blocked in the presence of an anti-rat IGF II receptor antibody. We conclude that IGF II affects tissue-specific gene expression of hepatomas and qualitative and quantitative aspects of its influence on the hepatomas is dependent on their degree of differentiation.

Albumins↗

PubMed1988

Stability of visual acuity in amblyopic patients after visual maturity.

One hundred thirty patients with strabismic amblyopia who underwent full-time occlusion therapy (FTO) and were followed through to at least 9 years of age were evaluated to determine the stability of visual acuity after visual maturity (after 9 years of age). Of these 130 patients, 89 are included in this review. At the conclusion of the FTO therapy, 92% (82/89) had attained a visual acuity of 20/40 or better, 6% (5/89) had attained 20/50-20/100, and 2% (2/89) remained at 20/200 or less. Of the nine patients in this series in whom patching was initiated between the ages of 6 and 9 years of age, a good visual result was seen in 89% (8/9), with 63% (5/8) of those attaining 20/20 vision. The final visual acuity in this group of patients was taken at an average patient age of 15.9 years. In 75% of the patients (67/89) there was no change in visual acuity over time, while 17% (15/89) showed a one- or two-line decrease, and in 8% (7/89) vision dropped more than two lines. Of those patients who had greater than or equal to 20/40, 88% (56/64) who had a posttreatment visual acuity of 20/20 showed no change at the final evaluation, but only 50% (9/18) of those whose posttreatment vision was between 20/25 and 20/40 were stable. In those patients who needed part-time occlusion (PTO) to maintain equal visual acuity, their stability appeared to be the same as the vision of those whose vision was maintained without PTO.

Adolescent↗

PubMed2006

In vivo footprinting of the carbamoylphosphate synthetase I cAMP-response unit indicates important roles for FoxA and PKA in formation of the enhanceosome.

The expression of carbamoylphosphate synthetase-I (CPS), the first and rate-determining enzyme of the urea cycle, is regulated at the transcriptional level by glucocorticoids and glucagon, the latter acting via cyclic AMP (cAMP). The hormonal response is mediated by a distal enhancer located 6.3 kb upstream of the transcription-start site. Within this enhancer, a cAMP-response unit (CRU) is responsible for mediating cAMP-dependent transcriptional activity. The CPS CRU contains binding sites for cAMP-response element (CRE)-binding protein (CRE-BP), forkhead box A (FoxA), CCAAT/enhancer-binding protein (C/EBP), and an unidentified protein P1. To gain insight in the protein-DNA interactions that activate the CPS CRU in living cells, we have employed in vivo footprinting assays. Comparison of the fibroblast cell line Rat-1 and the hepatoma cell lines FTO-2B and WT-8 showed that FoxA binds the CPS CRU constitutively in CPS-expressing cells only. Comparison of FTO-2B and WT-8 hepatoma cells, which only differ in cAMP responsiveness, demonstrated that the binding of the other transcription factors is dependent on cAMP-dependent protein kinase (PKA) activity. Finally, we observed a footprint between the CRE and the P1-binding site in the in vivo footprint assay that was not detectable by in vitro footprint assays, implying a major change in CRU-associated chromatin conformation upon CRU activation. These findings indicate that activation of the CRU is initiated in a tissue-specific manner by the binding of FoxA. When cellular cAMP and glucocorticoid levels increase, CRE-BP becomes activated, allowing the binding of the remaining transcription factors and the transactivation of the CPS promoter.

Animals↗

PubMedDate not supplied

Tumor necrosis factor in peritoneal fluid from asymptomatic infertile women.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is a cytokine that can be found in the peritoneal fluid (PF) of patients with endometriosis and pelvic inflammatory disease (PID) as a response to inflammatory disorders and infections. The cytotoxic effect of this cytokine could be a factor participating in the pathology of various gynecological diseases, and could also be accountable for the high immunological response and damage to the tubal epithelium. The objective of this study was to establish the presence of TNF-alpha in asymptomatic infertility and its association with various isolated bacteria. METHODS: Ten milliliters of PF were collected from each of 73 patients by means of laparoscopy and cultured in synthetic medium and McCoy cells for the isolation of aerobic and anaerobic bacteria, as well as for Chlamydia trachomatis. The activity of TNF-alpha was determined by means of a bioassay using L-929 cells. RESULTS: Forty-three percent of the PFs showed positive TNF-alpha activity, while the laparoscopic evaluation showed that 32 patients had Fallopian tube occlusion (FTO), 7 had endometriosis, 30 had PID, and 4 had myomas and adhesions. TNF-alpha activity was found to be high in FTO patients (p < 0.05). Positive cultures were found in 50.7% of patients; of these, 31.5% had PID (p < 0.05), and only 20.5% of positive cultures were TNF-alpha positive. Chlamydia trachomatis (16%) was the most frequently isolated bacteria in these patients. CONCLUSIONS: The detection of TNF-alpha could be useful in the diagnosis of active infectious and inflammatory diseases in asymptomatic infertile patients.

Adolescent↗

PubMed1997

Suppression of phospholipase C beta, gamma, and delta families alters cell growth and phosphatidylinositol 4,5-bisphosphate levels.

Phosphatidylinositol-specific phospholipase C (PLC) activity reflects a summation of the activities of three families, beta, gamma, and delta, each of which is regulated differently. In order to understand the contribution of each family to cell proliferation signaling, expression of each family was suppressed by use of an inducible expression vector for antisense PLC sequences in a single cell line, FTO-2B rat hepatocytes. Activation of second messengers of PLC [diacylglycerol (DAG) and inositol 1,4,5-tris(phosphate) (IP3)] was dramatically reduced, providing a strategy for probing the consequences of PLC deficiency on cell function. Importantly, while one PLC family was suppressed, the other PLCs actively responded to specific stimuli, suggesting parallel and independent signaling pathways for each PLC family in FTO-2B cells. Selective suppression of each PLC family altered cell growth markedly and differentially. The rank order for suppression of cell growth by loss of a PLC family was gamma > delta > beta. Exploration of down-stream growth regulators revealed that loss of beta and gamma, but not delta, families was associated with markedly reduced basal ras and protein kinase C activity. Moreover, suppression of each of the three PLC families caused remarkably reduced basal and stimulated MAP kinase activities. Interestingly, cellular levels of PIP2 were increased and dramatically correlated with growth inhibition rate in the clones with suppressed PLC activity, suggesting that PIP2 itself can serve as a second messenger of cell growth regulation.

Animals↗