| origin and possible roles of the sox8 transcription factor gene during sexual development. | sox8 is a member of the sox family of developmental transcription factor genes and is closely related to sox9, a critical gene involved in mammalian sex determination and differentiation. both genes encode proteins with the ability to bind similar dna target sequences, and to activate transcription in in vitro assays. expression studies indicate that the two genes have largely overlapping patterns of activity during mammalian embryonic development. a knockout of sox8 in mice has no obvious devel ... | 2003 | 14684985 |
| dendritic cells in rheumatoid arthritis. | dendritic cells are the most potent subset of antigen presenting cells. they are derived from bone marrow stem cells and reside in peripheral tissues or blood. upon exposure to antigens and cytokines the peripheral dc s, express high amounts of peptide-mhc, and upregulate their costimulatory molecules, migrate to draining lymph nodes, and interact with t cells to stimulate or tolerize them. dendritic cells have been found in synovium and joint fluid in rheumatoid arthritis, often at the center o ... | 2005 | 15569606 |
| tissue-distribution of aldehyde dehydrogenase 2 and effects of the aldh2 gene-disruption on the expression of enzymes involved in alcohol metabolism. | in alcohol metabolism, acetaldehyde, a highly reactive intermediate that may cause cellular and dna damages, is converted to acetate by mitochondrial aldehyde dehydrogenase aldh2. although the majority of ingested alcohol is eliminated in the liver, the first-pass metabolism of ethanol in the upper digestive tract is also important for prevention and management of ethanol-related gastrointestinal diseases. however, the tissue-distribution of aldh2 in mice has been poorly investigated. in this st ... | 2005 | 15569633 |
| ligand epitope antigen presentation system vaccines against herpes simplex virus. | the ligand epitope antigen presentation system (l.e.a.p.s.) approach to vaccine development allowed construction of immunogens from defined t cell epitopes from herpes simplex virus (hsv) proteins that conferred protection against lethal challenge by the virus. this technology utilizes specific peptides which bind to cd4, cd8 or other proteins on the surface of t cells (t cell binding ligand (tcbl)), macrophage and dendritic cells (immune cell binding ligand (icbl)) to promote the immunogenicity ... | 2005 | 15569635 |
| radioprotective effect of abana, a polyherbal drug following total body irradiation. | effects of 20 mg/kg body weight of abana (abe) on radiation-induced sickness and mortality in mice exposed to 7 gy to 12 gy of gamma irradiation were studied. treatment of mice with abana 1 h before irradiation delayed the onset of mortality and reduced the symptoms of radiation sickness when compared with the non-drug treated irradiated controls (double distilled water, ddw). abana provided protection against both the gastrointestinal and haemopoietic deaths. however, animals of both the abe+ir ... | 2004 | 15569645 |
| heart-directed expression of a human cardiac isoform of camp-response element modulator in transgenic mice. | the transcriptional activation mediated by camp-response element (cre) and transcription factors of the cre-binding protein (creb)/cre modulator (crem) family represents an important mechanism of camp-dependent gene regulation possibly implicated in detrimental effects of chronic beta-adrenergic stimulation in end-stage heart failure. we studied the cardiac role of crem in transgenic mice with heart-directed expression of crem-ibdeltac-x, a human cardiac crem isoform. transgenic mice displayed a ... | 2005 | 15569686 |
| impaired ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice. | sarcalumenin (sar), specifically expressed in striated muscle cells, is a ca2+-binding protein localized in the sarcoplasmic reticulum (sr) of the intracellular ca2+ store. by generating sar-deficient mice, we herein examined its physiological role. the mutant mice were apparently normal in growth, health, and reproduction, indicating that sar is not essential for fundamental muscle functions. sar-deficient skeletal muscle carrying irregular sr ultrastructures retained normal force generation bu ... | 2005 | 15569689 |
| blockade of psgl-1 attenuates cd14+ monocytic cell recruitment in intestinal mucosa and ameliorates ileitis in samp1/yit mice. | the pathogenesis of crohn's disease (cd) is not known. however, monocytes and macrophages are thought to play important roles in the development of mucosal inflammation. therefore, in this study, we examined the role of monocyte-endothelial cell interactions in senescence-accelerated mouse p1 (samp1)/yit mice, a murine model of spontaneous ileitis. fluorescence-labeled cd14+ monocytic cells isolated from the spleen and mesenteric lymph nodes of akr/j (control) mice were injected into the tail ve ... | 2005 | 15569697 |
| the capacity of the natural ligands for cd28 to drive il-4 expression in naïve and antigen-primed cd4+ and cd8+ t cells. | the b7/cd28 costimulatory pathway plays a critical role in t cell activation including th1/th2 differentiation. however, little is known about whether cd28 costimulation favors polarization of either th1 and th2 or both. here, we show a critical role of the natural ligands for cd28 molecules (b7.2-ig or b7.1-ig fusion proteins), particularly in the induction of type 2 t cell polarization. upon tcr-triggering with suboptimal doses of anti-cd3, costimulation of naïve cd4+ t cells with anti-cd28 ma ... | 2005 | 15569772 |
| pregnancy-induced alterations of b cell maturation and survival are differentially affected by fas and bcl-2, independently of bcr expression. | in the present work, we have analyzed the roles of two molecules involved in the regulation of cell survival, bcl2 and fas, in the pregnancy-induced down-regulation of b lymphopoiesis in mice. our results show that the overexpression of the anti-apoptotic molecule bcl2 in bcl2-transgenic (tg) b cells is able to protect 'd' fraction pre-b cells from pregnancy-induced deletion. in contrast, in fas(lpr/lpr) mice bearing a mutated cell death receptor fas, such b cell targets are not protected. moreo ... | 2005 | 15569774 |
| oxidative stress in atherosclerosis-prone mouse is due to low antioxidant capacity of mitochondria. | atherosclerotic disease remains a leading cause of death in westernized societies, and reactive oxygen species (ros) play a pivotal role in atherogenesis. mitochondria are the main intracellular sites of ros generation and are also targets for oxidative damage. here, we show that mitochondria from atherosclerosis-prone, hypercholesterolemic low-density lipoprotein (ldl) receptor knockout mice have oxidative phosphorylation efficiency similar to that from control mice but have a higher net produc ... | 2005 | 15569776 |
| rapid detection of malaria infection in vivo by laser desorption mass spectrometry. | rapid diagnosis leading to effective treatment is essential to control escalating infectious diseases such as malaria. malaria pigment (hemozoin) detection by laser desorption mass spectometry (ldms) was recently shown to be a sensitive (<10 parasites/mul) technique for detecting plasmodium falciparum parasites cultured in human blood. to examine the use of ldms in a rapid new malaria screening assay, we followed the time course of p. yoelii infections in mice in parallel with light microscopy a ... | 2004 | 15569781 |
| characterization of the early cellular immune response to leishmania major using peripheral blood mononuclear cells from leishmania-naive humans. | while the response to leishmania major is well characterized in mice, there is much less known about the human immune response, particularly early after exposure to the parasite. therefore, we developed a primary in vitro (piv) system that allowed us to address these questions. we co-cultured peripheral blood mononuclear cells from leishmania-naive donors with l. major parasites and found that the responding piv cells produced interferon-gamma and interleukin-12 (il-12). when restimulated, these ... | 2004 | 15569786 |
| inhibition of triglyceride synthesis as a treatment strategy for obesity: lessons from dgat1-deficient mice. | because the ability to make triglycerides is essential for the accumulation of adipose tissue, inhibition of triglyceride synthesis may ameliorate obesity and its related medical consequences. acyl coenzyme a (coa):diacylglycerol acyltransferase 1 (dgat1) is 1 of 2 dgat enzymes that catalyze the final reaction in the known pathways of mammalian triglyceride synthesis. mice lacking dgat1 are resistant to obesity and have increased sensitivity to insulin and leptin. dgat1-deficient mice are also r ... | 2005 | 15569818 |
| bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. | recent studies in mice have challenged the ability of bone marrow cells (bmcs) to differentiate into myocytes and coronary vessels. the claim has also been made that bmcs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. technical problems exist in the induction of myocardial infarction and the successful injection of bmcs in the mouse heart. similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is ... | 2005 | 15569828 |
| prenatal environmental tobacco smoke exposure promotes adult atherogenesis and mitochondrial damage in apolipoprotein e-/- mice fed a chow diet. | environmental tobacco smoke (ets) exposure is recognized as a cardiovascular disease risk factor; however, the impact of prenatal ets exposure on adult atherogenesis has not been examined. we hypothesized that in utero ets exposure promotes adult atherosclerotic lesion formation and mitochondrial damage. | 2004 | 15569831 |
| overexpression of wild-type heat shock protein 27 and a nonphosphorylatable heat shock protein 27 mutant protects against ischemia/reperfusion injury in a transgenic mouse model. | the small heat shock protein 27 (hsp27) increases in expression with ischemia/reperfusion (i/r) insult in the heart. one feature of the small hsps is their ability to oligomerize and form intracellular aggregates. oligomerization pattern is governed by the phosphorylation state of the protein that may influence their ability to protect against cellular stresses. | 2004 | 15569832 |
| factor vleiden inhibits fibrinolysis in vivo. | factor v(leiden) (fv(leiden)) predisposes to thrombosis by enhancing thrombin formation. this study tested the hypothesis that fv(leiden) inhibits fibrinolysis in vivo. | 2004 | 15569834 |
| toll-like receptor 2 mediates staphylococcus aureus-induced myocardial dysfunction and cytokine production in the heart. | staphylococcus aureus sepsis is associated with significant myocardial dysfunction. toll-like receptor 2 (tlr2) mediates the inflammatory response to s aureus and may trigger an innate immune response in the heart. we hypothesized that a tlr2 deficiency would attenuate s aureus-induced cardiac proinflammatory mediator production and the development of cardiac dysfunction. | 2004 | 15569836 |
| thrombin stimulates human endothelial arginase enzymatic activity via rhoa/rock pathway: implications for atherosclerotic endothelial dysfunction. | arginase competes with endothelial nitric oxide synthase (enos) for the substrate l-arginine and decreases no production. this study investigated regulatory mechanisms of arginase activity in endothelial cells and its role in atherosclerosis. | 2004 | 15569838 |
| signaling via the angiotensin-converting enzyme enhances the expression of cyclooxygenase-2 in endothelial cells. | angiotensin-converting enzyme (ace) inhibitors elicit outside-in signaling via ace in endothelial cells. this involves the ck2-mediated phosphorylation of ace on ser1270 and the activation of the c-jun n-terminal kinase (jnk)/c-jun pathway, resulting in an enhanced endothelial ace expression. because cyclooxygenase-2 (cox-2) expression is reported to be increased in subjects treated with ace inhibitors, we determined the role of ace signaling in this phenomenon and the transcription factors invo ... | 2005 | 15569856 |
| impaired vascular mechanotransduction in a transgenic mouse model of cadasil arteriopathy. | cadasil is an inherited small-vessel disease responsible for lacunar strokes and cognitive impairment. the disease is caused by highly stereotyped mutations in notch3, the expression of which is highly restricted to vascular smooth muscle cells (vsmcs). the underlying vasculopathy is characterized by degeneration of vsmcs and the accumulation of granular osmiophilic material (gom) and notch3 protein within the cell surface of these cells. in this study, we assessed early functional changes relat ... | 2005 | 15569862 |
| a critical role for p27kip1 gene dosage in a mouse model of prostate carcinogenesis. | in human prostate cancer, the frequent down-regulation of p27(kip1) protein expression is correlated with poor clinical outcome, yet p27(kip1) rarely undergoes mutational inactivation. here, we investigate the consequences of reducing or eliminating p27(kip1) function for prostate carcinogenesis in the context of a mouse modeling lacking the nkx3.1 homeobox gene and the pten tumor suppressor. unexpectedly, we find that triple mutant mice heterozygous for a p27(kip1) null allele (nkx3.1(+/- or -/ ... | 2004 | 15569926 |
| tyrosine phosphorylation sites on frs2alpha responsible for shp2 recruitment are critical for induction of lens and retina. | early development of the lens and retina depends upon reciprocal inductive interactions between the embryonic surface ectoderm and the underlying neuroepithelium of the optic vesicle. fgf signaling has been implicated in this signal exchange. the docking protein frs2alpha is a major mediator of fgf signaling by providing a link between fgf receptors (fgfrs) and a variety of intracellular signaling pathways. after fgf stimulation, tyrosine-phosphorylated frs2alpha recruits four molecules of the a ... | 2004 | 15569927 |
| neurochemical and behavioral consequences of widespread gene knockdown in the adult mouse brain by using nonviral rna interference. | gene expression analysis implicates an increasing number of novel genes in the brain as potential targets for the treatment of neurological and psychiatric disorders. frequently, these genes are ubiquitously expressed in the brain and, thus, may contribute to a pathophysiological state through actions in several brain nuclei. current strategies employing genetically modified animals for in vivo validation of such targets are time-consuming and often limited by developmental adaptations. somatic ... | 2004 | 15569935 |
| restricted inactivation of serum response factor to the cardiovascular system. | serum response factor (srf) directs programs of gene expression linked to growth and muscle differentiation. to investigate the role of srf in cardiovascular development, we generated mice in which srf is knocked out in >80% of cardiomyocytes and >50% of vascular smooth muscle cells (smc) through sm22alpha-cre-mediated excision of srf's promoter and first exon. mutant mice display vascular patterning, cardiac looping, and srf-dependent gene expression through embryonic day (e)9.5. at e10.5, atte ... | 2004 | 15569937 |
| identification and modulation of a caveolae-dependent signal pathway that regulates plasminogen activator inhibitor-1 in insulin-resistant adipocytes. | plasminogen activator inhibitor-1 (pai-1) plays an important role in the pathogenesis of obesity-driven type 2 diabetes mellitus and associated cardiovascular complications. here, we show that perturbation of caveolar microdomains leads to insulin resistance and concomitant up-regulation of pai-1 in 3t3l1 adipocytes. we present several lines of evidence showing that the phosphatidylinositol 3-kinase (pi3k) pathway negatively regulates pai-1 gene expression. insulin-induced pai-1 gene expression ... | 2004 | 15569940 |
| targeted disruption of luteinizing hormone beta-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. | luteinizing hormone (lh) and follicle-stimulating hormone (fsh) act on gonadal cells to promote steroidogenesis and gametogenesis. clarifying the in vivo roles of lh and fsh permits a feasible approach to contraception involving selective blockade of gonadotropin action. one way to address these physiologically important problems is to generate mice with an isolated lh deficiency and compare them with existing fsh loss-of-function mice. to model human reproductive disorders involving loss of lh ... | 2004 | 15569941 |
| differential radiosensitization in dna mismatch repair-proficient and -deficient human colon cancer xenografts with 5-iodo-2-pyrimidinone-2'-deoxyribose. | 5-iodo-2-pyrimidinone-2'-deoxyribose (ipdr) is a pyrimidinone nucleoside prodrug of 5-iododeoxyuridine (iudr) under investigation as an orally administered radiosensitizer. we previously reported that the mismatch repair (mmr) proteins (both hmsh2 and hmlh1) impact on the extent (percentage) of iudr-dna incorporation and subsequent in vitro iudr-mediated radiosensitization in human tumor cell lines. in this study, we used oral ipdr to assess in vivo radiosensitization in mmr-proficient (mmr+) an ... | 2004 | 15569982 |
| inactivation of the fhit gene favors bladder cancer development. | the fragile histidine triad (fhit) gene located on chromosome 3p14.2 is frequently deleted in human tumors. we have previously reported deletions at the fhit locus in 50% of bladder carcinoma derived cell lines and reduced expression in 61% of primary transitional carcinomas of the urinary bladder. to additionally investigate the role of fhit alterations in the development of bladder cancer, we used heterozygous and nullizygous fhit-deficient mice in a chemically induced carcinogenesis model. re ... | 2004 | 15569992 |
| granulin-epithelin precursor overexpression promotes growth and invasion of hepatocellular carcinoma. | granulin-epithelin precursor (gep) is a novel growth factor. our earlier cdna microarray study indicated that gep was overexpressed in hepatocellular carcinoma (hcc). the aim of this study was to investigate the clinical significance of gep expression and its potential as a therapeutic target in hcc. | 2004 | 15569995 |
| inhibition of inhibitor of nuclear factor-kappab phosphorylation increases the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. | we investigated whether inhibition of nuclear factor-kappab (nfkappab) increases the efficacy of paclitaxel in in vitro and in vivo ovarian cancer models. treatment of paclitaxel-sensitive caov-3 cells with paclitaxel transiently activated the phosphorylation of akt, the phosphorylation of ikappab kinase (ikk), and the phosphorylation of inhibitor of nfkappab (ikappabalpha). paclitaxel also caused a transient increase in nfkappab activity, followed by a decrease in nfkappab activity. we show an ... | 2004 | 15569997 |
| the effects of taurolidine, a novel antineoplastic agent, on human malignant mesothelioma. | malignant mesothelioma (mm) is a cancer with uniformly poor responses to current therapeutic regimens. this study evaluates whether taurolidine, a novel antineoplastic agent, is effective against human mm cell lines and a murine model of human mm. | 2004 | 15569998 |
| antitumor efficacy of oblimersen bcl-2 antisense oligonucleotide alone and in combination with vinorelbine in xenograft models of human non-small cell lung cancer. | overexpression of bcl-2 protein in cancer cells can inhibit programmed cell death and engender chemoresistance. reducing bcl-2 protein levels by using antisense oligonucleotides targeting the gene message can increase the sensitivity of cancer cells to cytotoxic agents. the objective of this work was to investigate the antitumor efficacy of the bcl-2 antisense oligonucleotide oblimersen (genasense; g3139), alone and in combination with vinorelbine (vnb), in an ectopic and orthotopic xenograft mo ... | 2004 | 15569999 |
| sensitization of tumor-associated endothelial cell apoptosis by the novel vascular-targeting agent zd6126 in combination with cisplatin. | zd6126 is a novel vascular-targeting agent that selectively disrupts the tubulin cytoskeleton of endothelial cells. in the immature vessels characteristic of tumor vasculature, this leads to endothelial cell contraction, blood vessel congestion, and, consequently, tumor cell death. zd6126 has been shown to delay tumor growth in a range of xenograft models. the antitumor effect of zd6126 can be increased in combination with cisplatin or radiation therapy, although the precise mechanism of this en ... | 2004 | 15570000 |
| inhibition of metastatic tumor growth in mouse lung by repeated administration of polyethylene glycol-conjugated catalase: quantitative analysis with firefly luciferase-expressing melanoma cells. | to develop a novel and effective approach to inhibit tumor metastasis based on controlled delivery of catalase, we first evaluated the characteristics of the disposition and proliferation of tumor cells. then, we examined the effects of polyethylene glycol-conjugated catalase (peg-catalase) on tumor metastasis. on the basis of the results obtained, peg-catalase was repetitively administered to completely suppress the growth of tumor cells. | 2004 | 15570002 |
| species differences in troxacitabine pharmacokinetics and pharmacodynamics: implications for clinical development. | troxacitabine is the first unnatural l-nucleoside analog to show potent preclinical antitumor activity and is currently under clinical investigation. significant differences in troxacitabine toxicity between mice, rats, monkeys, and humans were observed during preclinical and clinical evaluations. to better understand the different toxicity and efficacy results observed between the human xenograft mouse tumor models used for preclinical assessment and the clinical study results, the pharmacodyna ... | 2004 | 15570003 |
| dietary flaxseed enhances the inhibitory effect of tamoxifen on the growth of estrogen-dependent human breast cancer (mcf-7) in nude mice. | this study determined the effect of 10% dietary flaxseed (fs) and tamoxifen (tam), alone and in combination, on the growth of estrogen-dependent human breast cancer (mcf-7) in athymic mice with or without 17beta-estradiol (e2) supplementation. | 2004 | 15570004 |
| regression of mouse prostatic intraepithelial neoplasia by nonsteroidal anti-inflammatory drugs in the transgenic adenocarcinoma mouse prostate model. | epidemiologic studies have revealed a decreased risk of colon cancer among people who have regularly taken cyclooxygenase (cox)-2 inhibitors such as aspirin or other nonsteroidal anti-inflammatory drugs (nsaids). whereas the selective cox-2 inhibitor celecoxib and exisulind, a metabolic product of sulindac, have gained increasing attention as efficacious chemopreventive agents against colon and prostate cancer, not much is known about the underlying molecular targets and mechanisms. moreover, th ... | 2004 | 15570007 |
| vector targeting makes 5-fluorouracil chemotherapy less toxic and more effective in animal models of epithelial neoplasms. | 5-fluorouracil (5-fu) has been combined in the past with other drugs for the combination chemotherapy for cancers of the breast, ovary, and colon. these drug regimens were limited by the fact that 5-fu fails to kill nondividing cancer cells at the doses that are safe to deliver. the goal of the present study is to test the feasibility of replacing 5-fu in established 5-fu combination chemotherapy with the ad-lpcdirese1a/5-fluorocytosine (5-fc) system for the purpose of reducing toxicity and incr ... | 2004 | 15570008 |
| autocrine motility factor signaling enhances pancreatic cancer metastasis. | autocrine motility factor (amf)/phosphoglucose isomerase (pgi) is a ubiquitous cytosolic enzyme that plays a key role in glycolysis. amf/pgi is also a multifunctional protein that acts in the extracellular milieu as a potent mitogen/cytokine. increased expression of amf/pgi and its receptor has been found in a wide spectrum of malignancies and is associated with cancer progression and metastasis. recent studies indicated that amf is induced by hypoxia and enhances the random motility of pancreat ... | 2004 | 15570012 |
| five cysteine-containing compounds delay diabetic deterioration in balb/ca mice. | the effects of n-acetyl cysteine (nac), s-allyl cysteine (sac), s-ethyl cysteine, s-methyl cysteine and s-propyl cysteine (spc) activity on balb/ca mice against diabetic complications were examined. these complications included hyperglycemia, hyperlipidemia, oxidation stress, blood coagulation, and cytokine imbalance. to induce diabetes, mice were treated with streptozotocin i.p. for 5 consecutive days. five cysteine-containing compounds at 1 g/l were added to the drinking water. after intake of ... | 2004 | 15570020 |
| soluble fibroin enhances insulin sensitivity and glucose metabolism in 3t3-l1 adipocytes. | type 2 diabetes is characterized by hyperglycemia and hyperinsulinemia, features of insulin resistance. in vivo treatment of ob/ob mice with hydrolyzed fibroin reverses these pathological attributes. to explore the mechanism underlying this effect, we used the murine, 3t3-l1 adipocyte cell line, which has been used extensively to model adipocyte function. chronic exposure of 3t3-l1 adipocytes to insulin leads to a 50% loss of insulin-stimulated glucose uptake. chronic exposure to different prepa ... | 2004 | 15570022 |
| metabolic adaptations of three inbred strains of mice (c57bl/6, dba/2, and 129t2) in response to a high-fat diet. | although it is now becoming more evident that the strain of mouse used to generate genetically modified models for the study of endocrine disorders contributes to the ensuing phenotype, metabolic characterization of these common strains used to produce genetically altered mice has been limited. the aim of this study therefore was to measure various metabolic parameters in c57bl/6, dba/2, and 129t2 mice fed a control or a high-fat diet. mice were fed either a control (7 g/100 g) or a high-fat (60 ... | 2004 | 15570023 |
| docosahexaenoic acid attenuates mycotoxin-induced immunoglobulin a nephropathy, interleukin-6 transcription, and mitogen-activated protein kinase phosphorylation in mice. | the purpose of this investigation was to evaluate the dose-dependent effects of docosahexaenoic acid (dha) on deoxynivalenol (don)-induced iga nephropathy in mice and their relation to proinflammatory gene expression and mitogen-activated protein kinase (mapk) activation. consumption of a modified ain-93g diet containing 1, 5, and 30 g/kg dha resulted in dose-dependent increases of dha in liver phospholipids with concomitant decreases in arachidonic acid compared with control diets. dha dose dep ... | 2004 | 15570035 |
| effects of energy balance on cancer in genetically altered mice. | evidence has accumulated from laboratory-based animal experiments and population-based human epidemiological studies that lifestyle factors that affect energy balance, such as caloric intake, nutritional status, and exercise, act in concert with genetic susceptibility to influence cancer development and progression. the use of animal models with specific genetic alterations, in combination with lifestyle modifications that alter overall energy balance, has contributed to a greater understanding ... | 2004 | 15570044 |
| (n-3) fatty acids and cancer therapy. | supplementing the diet of tumor-bearing mice or rats with oils containing (n-3) (omega-3) or with purified (n-3) fatty acids has slowed the growth of various types of cancers, including lung, colon, mammary, and prostate. the efficacy of cancer chemotherapy drugs such as doxorubicin, epirubicin, cpt-11, 5-fluorouracil, and tamoxifen, and of radiation therapy has been improved when the diet included (n-3) fatty acids. some potential mechanisms for the activity of (n-3) fatty acids against cancer ... | 2004 | 15570049 |
| vitamin d and colon carcinogenesis. | colorectal cancer is the third most commonly occurring cancer in the united states and accounts for approximately 11% of cancer deaths. many epidemiological studies have shown an association between dietary factors, including calcium and vitamin d, and the incidence of colon cancer. recently the calcium polyp prevention study demonstrated that calcium supplementation can reduce the recurrence of colon polyps, but the effect depends on serum vitamin d levels. we used the apc(min) mouse model of i ... | 2004 | 15570055 |
| transcription factor nrf2 is essential for induction of nad(p)h:quinone oxidoreductase 1, glutathione s-transferases, and glutamate cysteine ligase by broccoli seeds and isothiocyanates. | cruciferous vegetables contain glucosinolates that, after conversion to isothiocyanates (itc), are capable of inducing cytoprotective genes. we examined whether broccoli seeds can elicit a chemoprotective response in mouse organs and rodent cell lines and investigated whether this response requires nuclear factor-erythroid 2 p45-related factor 2 (nrf2). the seeds studied contained glucosinolate at 40 mmol/kg, of which 59% comprised glucoiberin, 19% sinigrin, 8% glucoraphanin, and 7% progoitrin. ... | 2004 | 15570060 |
| cnr/pcdhalpha family in subplate neurons, and developing cortical connectivity. | the cadherin-related neuronal receptor (cnr)/protocadherin (pcdh) alpha family is one of the diverse protocadherin families identified as a candidate diversified membrane-associated component regulating the formation of neuronal connectivity. however, its expression during neural circuit formation has not been examined in detail. here, we used a conserved sequence to study the expression of this protein family during the development of neocortical connectivity, by immunohistochemistry and in sit ... | 2004 | 15570159 |
| restoration of axotomy-induced pacap gene induction in scid mice with cd4+ t-lymphocytes. | pacap is a neuropeptide with putative neuroprotective, regenerative, and immunomodulatory actions. pacap mrna is up-regulated in motor neurons following facial nerve axotomy in wild type, but not immunodeficient scid mice. because cd4+ lymphocytes appear to be neuroprotective in facial nerve and other injury models, we studied pacap gene expression in scid mice preinfused with cd4+ enriched splenocytes. whereas the mean number of pacap hybridizing neurons after axotomy was reduced by 75% in unin ... | 2004 | 15570170 |
| activation of ras in neurons modifies synaptic vesicle docking and release. | we have recently demonstrated that constitutive activation of ha-ras in differentiated neurons induces structural remodeling of both axons and dendrites in a transgenic mouse model (referred as synras mice). here we show that this activation of neuronal ras enhances docking of synaptic vesicles to active zones, thereby leading to an increase in the size of the readily releasable pool of vesicles, while the size of the total pool of synaptic vesicles remained unchanged. the morphological phenotyp ... | 2004 | 15570171 |
| apoe isoform affects ltp in human targeted replacement mice. | inheritance of the epsilon4 allele for apolipoprotein e (apoe) increases the risk of alzheimer disease and memory impairment, whereas epsilon2 decreases these risks compared with the most common epsilon3 allele, but the mechanism for these effects is unknown. long-term potentiation (ltp) is an experimentally induced increase in synaptic efficacy that models memory. using hippocampal slices from wild type (wt), apoe knockout (apoe-ko), and targeted replacement mice expressing human apoe2, e3, or ... | 2004 | 15570172 |
| control of hyperphagia prevents obesity in bdnf heterozygous mice. | reduced levels of bdnf in mice cause obesity and behavioral abnormalities including increased aggression and hyperactivity. while it has been shown that the obesity is in part caused by increased food consumption it is still not clear whether defects in other mechanisms involved in the control of body weight homeostasis can also affect this phenotype. here we report that mice with reduced levels of bdnf do not develop obesity and have normal blood glucose levels if fed over a prolonged period of ... | 2004 | 15570174 |
| staphylococcal enterotoxin a-induced hepatotoxicity is predominantly mediated by fas ligand (cd95l). | to determine the role of tumor necrosis factor alpha (tnf-alpha) and fas ligand (fasl, cd95l) in superantigen-induced and endotoxin-induced liver injury. | 2004 | 15570211 |
| radiation dose determines the degree of myeloid engraftment after nonmyeloablative stem cell transplantation. | a multivariate analysis of 121 dogs conditioned with 200, 100, or 50 cgy of total body irradiation (tbi) followed by hematopoietic stem cell transplantation from matched littermates showed that tbi dose was the only factor examined that was statistically significantly associated with the percentage of donor myeloid engraftment in stable long-term chimeras ( p = .008). to understand the direct effects of low-dose irradiation on hematopoietic stem/progenitor cells, nonirradiated and irradiated hum ... | 2004 | 15570251 |
| semiquantitative assessment of hindlimb movement recovery without intervention in adult paraplegic mice. | experimental laboratory investigation of hindlimb movement recovery in chronic paraplegic mice. | 2005 | 15570318 |
| determination of the in vivo pharmacokinetics of palladium-bacteriopheophorbide (wst09) in emt6 tumour-bearing balb/c mice using graphite furnace atomic absorption spectroscopy. | palladium-bacteriopheophorbide (wst09), a novel bacteriochlorophyll derivative, is currently being investigated for use as a photodynamic therapy (pdt) drug due to its strong absorption in the near-infrared region and its ability to efficiently generate singlet oxygen when irradiated. in this study, we determined the pharmacokinetics and tissue distribution of wst09 in female emt6 tumour-bearing balb/c mice in order to determine if selective accumulation of this drug occurs in tumour tissue. a t ... | 2004 | 15570387 |
| overexpression of igf-binding protein 5 alters mineral and matrix properties in mouse femora: an infrared imaging study. | the anabolic effects of insulin-like growth factors (igfs) are modulated by a family of igf-binding proteins (igfbps). among the six known igfbps, igfbp-5 is considered to play a role in bone formation. to investigate the effects of igfbp-5 on bone mineral and matrix properties, femurs from transgenic mice overexpressing igfbp-5 under the control of the osteocalcin promoter were evaluated by fourier transform infrared imaging (ftiri). analyses were done at the time of maximal osteocalcin express ... | 2005 | 15570402 |
| control of atm-/- thymic lymphoma cell proliferation in vitro and in vivo by dexamethasone. | ataxia telangiectasia (a-t) is an autosomal recessive disease in humans caused by mutations in the atm (a-t mutated) gene. the disease involves multiple organ systems, and is associated with a high incidence of leukemias and lymphomas that develop in childhood. we have reported previously that thymic lymphoma development in atm knockout (atm-/-) mice is associated with elevated spontaneous dna synthesis in thymocytes, and that dexamethasone (dex) attenuates the elevated dna synthesis and prevent ... | 2005 | 15570424 |
| ameliorative effect of ozone on cytokine production in mice injected with human rheumatoid arthritis synovial fibroblast cells. | rheumatoid arthritis (ra) is a chronic inflammatory disease characterized by invasion of hyperplastic synovial cells and progressive joint destruction. ozone therapy has been proposed as an immunomodulator and cellular metabolic activator which shows long-term anti-inflammatory effects and serves to reduce further the proinflammatory factors. we purified ra synovial fibroblast cells (ra-sfc) from patients and avoided contaminating macrophages by flow cytometry, then treated them with ozone. foll ... | 2005 | 15570426 |
| oncolytic herpes simplex virus mutants are more efficacious than wild-type adenovirus type 5 for the treatment of high-risk neuroblastomas in preclinical models. | high-risk neuroblastoma (nb) is incurable using current treatment regimens in the majority of patients. oncolytic virotherapy is a novel approach being tested for several types of adult cancers. | 2005 | 15570577 |
| mek inhibitors block aicar-induced maturation in mouse oocytes by a mapk-independent mechanism. | the present study was carried out to assess the possible role of mitogen-activated protein kinase (mapk) in the meiosis-inducing action of the amp-activated protein kinase (ampk) activator, 5-aminoimidazole-4-carboxamide 1-beta-ribofuranoside (aicar). cumulus cell-enclosed oocytes (ceo) or denuded oocytes (do) from immature, ecg-primed mice were cultured 4 hr in eagle's minimum essential medium containing dbcamp plus increasing concentrations of aicar or okadaic acid (oa). oa is a phosphatase in ... | 2005 | 15570612 |
| [sexual differences in a state systems of dna structure maintenance and generation of reactive oxygen species in somatic cells of mice 101/h reparation-defective strain and manifestation of these differences after exposure to ionizing radiation]. | to analyse a role of the factor of a genetic fundamentals of cells in formation of radiation-induced genome instability (rigi) we investigated a condition of dna pattern, content of superoxide anion-radical o2*- and a sum of reactive oxigen species (ros) (o2*-, oh*, h2o2), and also catalase activity in bone marrow cells of male and female mice of 101/h strain in the norm and at once after chronic (10 day) exposure to 200 mgy gamma-radiation. thus we based on conception about a significance of me ... | 2004 | 15571038 |
| [ex vivo epr investigation of metabolic changes in mice treated with radiotoxins]. | the effect of radiotoxins (rt), obtained from gamma-irradiated potato tubers, on mice have been investigated using ex vivo epr. parts of liver, lung, spleen, heart and kidney were used for investigation. the amount of the preparations injected was 0.2 ml, rt concentration varying from 0.1 to 1 ld100 (ld100 = 100 mg/kg). an intraperitoneal injection of rt in dose of 0.1 ld100 resulted in metabolic changes only in spleen. during 8 hours after injection a gradual depression of enzyme ribonucleotide ... | 2004 | 15571039 |
| [in vitro and ex vivo epr investigation of metabolic changes in blood under the action of radiotoxins obtained from irradiated potato tubers]. | the effect of radiotoxin (rt) obtained from y-irradiated potato tubes on blood of sheep and mice has been investigated by using in vitro and ex vivo epr. in experiments in vitro, the action of different preparations (rt, extract from unirradiated potato tubers, 1%-hcl or 30%-hydrogen peroxide) on sheep blood has been compared. it has been established that rt is an effective oxidant (like 1%-hcl) of haem iron that leads to an increase of the methemoglobin concentration. the specific peculiarity o ... | 2004 | 15571040 |
| [medical-prophylactic properties of the low-molecular-weight chitosan at environmental radiation injury]. | the possibility of the successful modification of radiation injury by chitosan with low molecular weight (10 kda) has been established under experimental conditions. the survival of mice increased up to 72.7 and 44.7% respectively at intravenous and intramuscular injection 30 min before gamma-irradiation with a dose 8 gy (ld97). in guinea pigs the effect was 50-52.6% at intravenous and 40% at intramuscular administration 1-3 h after irradiation with a dose 5 gy (ld90). radioprotective efficiency ... | 2004 | 15571043 |
| immucillins as antibiotics for t-cell proliferation and malaria. | the genetic deficiency of human pnp causes a specific immunodeficiency by inducing apoptosis in dividing t-cells. powerful inhibitors of pnp have been designed from the experimental determination of the transition state structure of pnps. the immucillins are transition state analogue inhibitors with kd values as low as 7 pm. in the presence of deoxyguanosine the immucillins kill activated human t-cells but not other cell types. the immucillins are orally available and of low toxicity to mice. im ... | 2004 | 15571250 |
| 6-[2-phosphonomethoxy)alkoxy]-2,4-diaminopyrimidines: a new class of acyclic pyrimidine nucleoside phosphonates with antiviral activity. | acyclic nucleoside phosphonate derivatives containing a pyrimidine base preferably bearing amino groups at c-2 and c-4 (dapym), and linked at the c-6 position to (s)-[3-hydroxy-2-(phosphonomethoxy)propoxy] (hpmpo), 2-(phosphonomethoxy) ethoxy (pmeo) or (r)-[2-(phosphonomethoxy)propoxy] (pmpo), display an antiviral sensitivity spectrum that closely mimic that of the parental (s)-hpmp-, pme- and (r)-pmp-purine derivatives. several pmeo-dapym derivatives proved as potent as pmea (adefovir) and (r)- ... | 2004 | 15571252 |
| antiproliferative activity and mechanism of action of fatty acid derivatives of gemcitabine in leukemia and solid tumor cell lines and in human xenografts. | gemcitabine is a deoxycytidine analog, which can be inactivated by deamination catalyzed by deoxycytidine deaminase (dcda). altered transport over the cell membrane is a mechanism of resistance to gemcitabine. to facilitate accumulation, the fatty acid derivative cp-4125 was synthesized. since, the fatty acid is acylated at the site of action of dcda, a decreased deamination was expected. cp-4125 was equally active as gemcitabine in a panel of rodent and human cell lines and in human melanoma xe ... | 2004 | 15571253 |
| early onset of lipofuscin accumulation in dystrophin-deficient skeletal muscles of dmd patients and mdx mice. | lipofuscin, the so-called ageing pigment, is formed by the oxidative degradation of cellular macromolecules by oxygen-derived free radicals and redox-active metal ions. usually it accumulates in post-mitotic, long-lived cells such as neurons and cardiac muscle cells. in contrast, it is rarely seen in either normal or diseased skeletal muscle fibres. in this paper, we report that lipofuscin accumulates at an early age in both human and murine dystrophic muscles. autofluorescent lipofuscin granule ... | 2004 | 15571326 |
| immunohistochemical demonstration of leptin in pancreatic islets of non-obese diabetic and cd-1 mice: co-localization in glucagon cells and its attenuation at the onset of diabetes. | leptin is a 16 kd polypeptide hormone produced predominantly by white adipose tissue and exerts profound effects on food intake and energy balance. more recent studies have shown extra sites of leptin production in human and rodent tissues and have ascribed additional roles for the hormone, e.g., in immune and reproductive functions. a role for the hormone has also been implicated in insulin-dependent diabetes mellitus in the non-obese diabetic (nod) mouse. however, whether leptin originates fro ... | 2004 | 15571328 |
| involvement of kappa-opioid receptors and sigma receptors in memory function demonstrated using an antisense strategy. | although antinociceptive effects of u-50,488h (trans-(+/-)-3,4-dichloro-n-methyl-n-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulfonate and (-)-pentazocine have been reported to influence kappa-opioid receptors, the involvement of kappa-opioid receptors in learning and/or memory is still controversial. we have recently reported that the memory improving effect of (-)-pentazocine was antagonized by sigma1 receptor antagonist. in this study, we examined the effects of several antisens ... | 2004 | 15571673 |
| p21(waf1/cip1) is not involved in kainic acid-induced apoptosis in murine cerebellar granule cells. | kainic acid (ka) treatment induced neuronal death and apoptosis in murine cerebellar granule cells (cgns) cultures from both wild-type and knockout p21(-/-) mice. there was not statistically significant difference in the percentage of neuronal apoptosis among strains. ka-induced neurotoxicity was prevented in the presence of nbqx (20 microm) and gyki 52446 (20 microm), but not by z-vad-fmk, suggesting that caspases are not involved in the apoptotic process. data suggest that p21(waf/cip) was una ... | 2004 | 15571679 |
| brain microglia and blood-derived macrophages: molecular profiles and functional roles in multiple sclerosis and animal models of autoimmune demyelinating disease. | microglia and macrophages, one a brain-resident, the other a mostly hematogenous cell type, represent two related cell types involved in the brain pathology in multiple sclerosis and its autoimmune animal model, the experimental allergic encephalomyelitis. together, they perform a variety of different functions: they are the primary sensors of brain pathology, they are rapidly recruited to sites of infection, trauma or autoimmune inflammation in experimental allergic encephalomyelitis and multip ... | 2004 | 15571769 |
| synthesis, antitumour and antimicrobial activities of new peptidyl derivatives containing the 1,3-benzodioxole system. | two series of 5 and 6-substituted 1,3-benzodioxole peptidyl derivatives were synthesized and evaluated as antitumour and antimicrobial agents. the compounds that could be conveniently prepared in a few steps processes from natural safrole have been characterised by ir and 1h-nmr spectroscopy. in vivo antitumor activity tests showed that some of the compounds were able to inhibit carcinoma s-180 tumour growth in mice. the in vitro antimicrobial activity of all compounds revealed that they are abl ... | 2004 | 15571867 |
| reovirus oncolysis in human head and neck squamous carcinoma cells. | to determine whether reovirus, a double-standed rna virus is effective on the growth of a human head and neck squamous cell carcinoma cell line. | 2004 | 15571915 |
| synthetic glycolipid och prevents insulitis and diabetes in nod mice. | non-obese diabetic (nod) mice develop diabetes mediated by pathogenic t-helper type 1 (th1) cells. v alpha 14 natural killer (nkt) cells are a unique lymphocyte subtype implicated in the regulation of autoimmunity and a good source of protective th2 cytokines. we recently developed a th2-skewing nkt cell ligand, och. och, a sphingosine truncated derivative of alpha-galactosylceramide (alpha-gc), stimulates nkt cells to selectively produce th2 cytokines. here we show that och prevented the develo ... | 2004 | 15571923 |
| cytokines activate caspase-3 in insulinoma cells of diabetes-prone nod mice directly and via upregulation of fas. | in type 1 diabetes, autoimmune inflammation of pancreatic islets of langerhans ('insulitis') results in destruction of insulin-producing beta cells. cytokines released from islet-infiltrating mononuclear cells are known to be cytotoxic both directly and by upregulating fas for fasl-induced apoptosis. to investigate the role of caspase-3, a major effector of apoptosis in beta-cell death, we asked whether cytokine- and/or fasl-induced apoptosis was associated with increased activity of caspase-3 i ... | 2004 | 15571924 |
| gene expression profiling in type 1 diabetes prone nod mice immunized with a disease protective autoantigenic peptide. | immunization with autoantigenic peptides skews t cell responses in type 1 diabetes (t1d), yet the gene-expression signature characterizing this change is unclear. we used cdna microarray technology to identify genes differentially regulated in splenocytes of t1d prone nod mice after immunization with a disease protective glutamic acid decarboxylase 65 (gad(65) p14) peptide. we identified 96 genes involved in cytokine secretion, humoral immune response, t cell activation, signal transduction, cel ... | 2004 | 15571925 |
| the effect of the phytoestrogen coumestrol on the nzb/w f1 murine model of systemic lupus. | coumestrol is a naturally occurring plant estrogen. as estrogen influences cellular and humoral immunity, and has known effects on murine models of lupus, we investigated the effect of coumestrol on disease expression in the nzb/w f1 mouse. female nzb/w f1 mice were fed a "standard" rodent diet including soy proteins, a non-soy diet, or a non-soy diet with 0.01% coumestrol. outcome measures included survival, autoantibody expression, immunoglobulin levels, proteinuria, renal histology and b cell ... | 2004 | 15571926 |
| igm monomers accelerate disease manifestations in autoimmune-prone fas-deficient mice. | the monomeric form of igm, also known as low molecular weight igm, is found in increased concentrations in patients chronically infected with a variety of viral and bacterial pathogens or suffering from various autoimmune diseases. whether monomeric igm contributes to the disease process, however, is not known. to address this question, transgenic mice were created that secreted elevated levels of igm monomers. in normal mice (c57bl/6), the presence of igm monomers did not alter the composition ... | 2004 | 15571927 |
| noninvasive in vivo whole body luminescent analysis of luciferase labelled orthotopic prostate tumours. | light photons refracted through living tissues can be used to noninvasively monitor the proliferation of cells expressing bioluminescent markers. we demonstrate the use of a luminometer for noninvasive in vivo whole body luminometric analysis (in vivo wbla) of luciferase-expressing prostate tumours growing orthotopically in nude mice, and thus hidden from visual inspection. in this procedure, the intraperitoneally (i.p.) inoculated luciferin, the luciferase substrate, reaches the tumours rapidly ... | 2004 | 15571970 |
| apoptotic neurodegeneration induced by ethanol in neonatal mice is associated with profound learning/memory deficits in juveniles followed by progressive functional recovery in adults. | administration of ethanol to rodents during the synaptogenesis period induces extensive apoptotic neurodegeneration in the developing brain. this neurotoxicity may explain the reduced brain mass and neurobehavioral disturbances in human fetal alcohol syndrome (fas). here, we report binge-like exposure of infant mice to ethanol on a single postnatal day triggered apoptotic death of neurons from diencephalic structures that comprise an extended hippocampal circuit important for spatial learning an ... | 2004 | 15571976 |
| impaired learning-dependent cortical plasticity in huntington's disease transgenic mice. | huntington's disease (hd) is a genetically transmitted neurodegenerative disorder. the neuropathology in hd is a selective neuronal cell death in several brain regions including cortex. although changes in synaptic plasticity were shown within the hippocampus and striatum of hd transgenic mice, there are no studies considering neocortical synaptic plasticity abnormalities in hd. we examined the impact of the hd transgene upon learning-dependent plasticity of cortical representational maps. the e ... | 2004 | 15571978 |
| insulin resistance contributes to aberrant stress responses in the tg2576 mouse model of alzheimer's disease. | we previously reported aberrant stress responses and impaired glucose tolerance in transgenic tg2576 mice, a model of alzheimer's disease (ad). here we report that by 8 months of age, tg2576 mice had lower basal serum insulin concentrations and exhibited a delayed insulin-induced reduction in blood glucose levels relative to wild-type mice. however, the basal levels of blood glucose and percent glycosylated hemoglobin (%hba1c) were similar between the two groups of mice. while the basal levels o ... | 2004 | 15571985 |
| longitudinal observation on csf abeta42 levels in young to middle-aged amyloid precursor protein/presenilin-1 doubly transgenic mice. | to relate levels of beta-amyloid42 (abeta42) in the cerebrospinal fluid (csf) and brain in early alzheimer's disease, we repeatedly measured csf abeta42 levels in transgenic mice carrying swedish amyloid precursor protein and presenilin-1 mutations, at ages before and after amyloid deposition. hippocampal abeta42 levels were measured at the endpoints. in appswe/ps1(a246e) mice, csf abeta42 levels significantly increased between 5 and 7 months of age but did not change between 8 and 13 months des ... | 2004 | 15571987 |
| gdnf-induced leukemia inhibitory factor can mediate differentiation via the mek/erk pathway in pheochromocytoma cells derived from nf1-heterozygous knockout mice. | glial cell line-derived neurotrophic factor (gdnf) can induce neuron-like differentiation of mouse pheochromocytoma (mpc) cell lines derived from mice with a heterozygous knockout mutation of nf1, the murine counterpart of the human gene mutated in neurofibromatosis type 1 (nf1). here, we show that gdnf-induced differentiation in the mpc 862l cell line is mediated by the mek/extracellular signal-regulated kinase (erk) pathway. neurite outgrowth, increased expression of growth-associated protein ... | 2005 | 15572029 |
| genetic modification of the heart: chaperones and the cytoskeleton. | in the past decade, genetic modification has been extensively employed to define (patho)physiological roles of chaperones and the cytoskeleton in the heart, promoting dramatic advances in this field. both loss-of-function and gain-of-function approaches have been used productively. alphab-crystallin (cryab) is the most abundant small heat shock protein (hsp) in the heart. a missense mutation (r120g) in cryab that is linked to human desmin-related myopathy (drm), has proved in transgenic (tg) mic ... | 2004 | 15572040 |
| genome-wide expression profiling of a cardiac pressure overload model identifies major metabolic and signaling pathway responses. | cardiac hypertrophy is a predictor of cardiovascular morbidity and mortality independent of other risk factors. pressure overload induces the development of left ventricular hypertrophy (lvh) and left atrial enlargement (lae) in the mammalian heart. to systematically investigate the transcriptional changes, which mediate these processes, we have performed a genome-wide transcriptional profiling of each of the four heart chambers from mice subjected to transverse aortic constriction (tac). a majo ... | 2004 | 15572046 |
| simvastatin enhances myocardial angiogenesis induced by vascular endothelial growth factor gene transfer. | statins have cardioprotective roles. we explored the cardiac angiogenic effects of simvastatin in combination with transient overexpression of vascular endothelial growth factor (vegf). compared with normal mice, 1-year-old apoe(-/-) mice fed on a high-fat diet (hfd) had about 30% less myocardial capillary (p < 0.001) and arteriolar (p < 0.03) densities, associated with decreased vegf (55%), vegfr-1 (56%) and vegfr-2 (78%) mrna expressions and myocardial endothelial nitric oxide synthase (enos) ... | 2004 | 15572054 |
| maintaining accuracy at the expense of speed: stimulus similarity defines odor discrimination time in mice. | odor discrimination times and their dependence on stimulus similarity were evaluated to test temporal and spatial models of odor representation in mice. in a go/no-go operant conditioning paradigm, discrimination accuracy and time were determined for simple monomolecular odors and binary mixtures of odors. mice discriminated simple odors with an accuracy exceeding 95%. binary mixtures evoking highly overlapping spatiotemporal patterns of activity in the olfactory bulb were discriminated equally ... | 2004 | 15572116 |
| positive regulation of myogenic bhlh factors and skeletal muscle development by the cell surface receptor cdo. | skeletal myogenesis is controlled by bhlh transcription factors of the myod family that, along with mef-2 factors, comprise a positive feedback network that maintains the myogenic transcriptional program. cell-cell contact between muscle precursors promotes myogenesis, but little is known of the underlying mechanisms. cdo, an ig superfamily member, is a component of a cell surface receptor complex found at sites of cell-cell contact that positively regulates myogenesis in vitro. we report here t ... | 2004 | 15572127 |
| the cellular and molecular etiology of the cleft secondary palate in fgf10 mutant mice. | mammalian palatogenesis depends on interactions between the stomodium-derived epithelium and the cranial neural crest-derived ectomesenchyme. fibroblast growth factor 10 (fgf10) is a mesenchymal signaling factor that guides the morphogenesis of multiple organs through tissue-tissue interactions. this is consistent with widespread agenesis and dysgenesis of organs observed in fgf10-/- mice. in this study, we report the presence of a wide-open cleft secondary palate in fgf10 homozygous null mutant ... | 2005 | 15572143 |
| identification of sox8 as a modifier gene in a mouse model of hirschsprung disease reveals underlying molecular defect. | mice carrying heterozygous mutations in the sox10 gene display aganglionosis of the colon and represent a model for human hirschsprung disease. here, we show that the closely related sox8 functions as a modifier gene for sox10-dependent enteric nervous system defects as it increases both penetrance and severity of the defect in sox10 heterozygous mice despite having no detectable influence on enteric nervous system development on its own. sox8 exhibits an expression pattern very similar to sox10 ... | 2005 | 15572147 |
| the axon guidance defect of the telencephalic commissures of the jsap1-deficient brain was partially rescued by the transgenic expression of jip1. | the jnk interacting protein, jsap1, has been identified as a scaffold protein for mitogen-activated protein kinase (mapk) signaling pathways and as a linker protein for the cargo transport along the axons. to investigate the physiological function of jsap1 in vivo, we generated mice lacking jsap1. the jsap1 null mutation produced various developmental deficits in the brain, including an axon guidance defect of the corpus callosum, in which phospho-fak and phospho-jnk were distributed at reduced ... | 2005 | 15572149 |
| excess biglycan causes eyelid malformation by perturbing muscle development and tgf-alpha signaling. | tissue morphogenesis during development is regulated by growth factors and cytokines, and is characterized by constant remodeling of extracellular matrix (ecm) in response to signaling molecules, for example, growth factors, cytokines, and so forth. proteoglycans that bind growth factors are potential regulators of tissue morphogenesis during embryonic development. in this study, we showed that transgenic mice overexpressing biglycan under the keratocan promoter exhibited exposure keratitis and ... | 2005 | 15572151 |
| distinctive functions of membrane type 1 matrix-metalloprotease (mt1-mmp or mmp-14) in lung and submandibular gland development are independent of its role in pro-mmp-2 activation. | membrane type 1-matrix metalloprotease (mt1-mmp or mmp-14) is a major activator of pro-mmp-2 and is essential for skeletal development. we show here that it is required for branching morphogenesis of the submandibular gland but not the lung. instead, in the lung, it is essential for postnatal development of alveolar septae. lung development in mmp14-/- mice is arrested at the prealveolar stage with compensatory hyperinflation of immature saccules. mmp2-/- mice lacked comparable defects in the lu ... | 2005 | 15572153 |
| corticotropin-releasing hormone and urocortin: redundant or distinctive functions? | neuropeptides play important roles in synaptic transmission. among them, the peptides of the corticotropin-releasing hormone (crh) family present interesting features. the two main mammalian peptides of this family, crh and urocortin (ucn), signal through the same receptors, crh-r1 and crh-r2. the question arises as to whether these peptides have redundant or distinctive functions. the fact that crh and ucn have high affinity for both receptors has hampered the possibility to define the function ... | 2004 | 15572167 |
| new insights into the expression and function of neural connexins with transgenic mouse mutants. | gap junctions represent direct intercellular conduits between contacting cells. the subunit proteins of these conduits are called connexins. to date, 20 and 21 connexin genes have been described in the mouse and human genome, respectively, many of them represent sequence-orthologous pairs. targeted deletion of connexin genes in the mouse genome opened new insights into the biological function of these channel forming proteins, which, in some cases, could be correlated to phenotypic abnormalities ... | 2004 | 15572175 |