MAGNETIC RESONANCE IN MEDICINE, Issue 4 2006
Richard A.E. Edden
Abstract In localized proton MR spectroscopy (1H-MRS) in vivo, the detection of lactate (Lac) is affected by modulation of its resonances due to homonuclear scalar couplings (J). A simple and convenient way to distinguish Lac from lipids is to set the TE to 1/J so that the Lac signal is inverted while other resonances (such as lipid) remain in-phase. However, at high field strengths, such as 3 Tesla or above, the modulation of the Lac signal is complicated by chemical shift effects that cause modulation patterns to vary within different subregions of the localized volume. Under some conditions the Lac signal may even disappear completely. In this note we introduce the concept of inner volume saturation (IVS), which makes use of high bandwidth spatial pulses to remove the signal corresponding to the regions of the localized volume that contribute unwanted modulation patterns. The method is described theoretically and demonstrated experimentally at 3 Tesla in a phantom and a patient with acute stroke. The phantom measurements indicate that virtually 100% of the Lac signal can be recovered using this method. The method should be feasible at magnetic fields above 3 Tesla, and may also be applied to other coupled spin systems in which modulation effects are important. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source]

Edge-roundness of boulders of Torridonian Sandstone (northwest Scotland): applications for relative dating and implications for warm and cold climate weathering rates

BOREAS, Issue 2 2010
MARTIN P. KIRKBRIDE
Kirkbride, M.P. & Bell, C.M. 2009: Edge-roundness of boulders of Torridonian Sandstone (northwest Scotland): applications for relative dating and implications for warm and cold climate weathering rates. Boreas, 10.1111/j. 1502-3885.2009.00131.x. ISSN 0300-9483. The relative ages of late Quaternary morainic and rock avalanche deposits on Late Precambrian Torridonian Sandstone are determined from the characteristic edge-roundness of constituent boulders. Because weathering of sandstone is manifest as edge-rounding by granular disintegration, a relative chronology can be derived by measuring the effective radii of curvature of a sample of boulder edges. Thirteen samples totalling 597 individual boulder edges fall into two statistically distinct groups. Moraines of inferred Younger Dryas age (12.9,11.5 kyr BP) are distinguished from moraines of the Wester Ross Re-advance (,14.0 kyr BP). One moraine previously assumed to be of Younger Dryas age is reassigned to the older group. The method allows spatial extrapolation of deposit ages from dated sites where lithological and sampling criteria are met. Calculated rates of edge-rounding imply that granular disintegration was several times more rapid during cold stadial climates than during the Holocene. Used as a proxy for boulder ,erosion rate', this indicates that surface loss of grains in glacial climates exceeds that during interglacials by a factor of 2,5, with implications for the calculation of exposure ages from cosmogenic nuclides. [source]

Impaired Pavlovian fear extinction is a common phenotype across genetic lineages of the 129 inbred mouse strain

GENES, BRAIN AND BEHAVIOR, Issue 8 2009
M. Camp
Fear extinction is impaired in psychiatric disorders such as post-traumatic stress disorder and schizophrenia, which have a major genetic component. However, the genetic factors underlying individual variability in fear extinction remain to be determined. By comparing a panel of inbred mouse strains, we recently identified a strain, 129S1/SvImJ (129S1), that exhibits a profound and selective deficit in Pavlovian fear extinction, and associated abnormalities in functional activation of a key prefrontal-amygdala circuit, as compared with C57BL/6J. The first aim of the present study was to assess fear extinction across multiple 129 substrains representing the strain's four different genetic lineages (parental, steel, teratoma and contaminated). Results showed that 129P1/ReJ, 129P3/J, 129T2/SvEmsJ and 129X1/SvJ exhibited poor fear extinction, relative to C57BL/6J, while 129S1 showed evidence of fear incubation. On the basis of these results, the second aim was to further characterize the nature and specificity of the extinction phenotype in 129S1, as an exemplar of the 129 substrains. Results showed that the extinction deficit in 129S1 was neither the result of a failure to habituate to a sensitized fear response nor an artifact of a fear response to (unconditioned) tone per se. A stronger conditioning protocol (i.e. five × higher intensity shocks) produced an increase in fear expression in 129S1, relative to C57BL/6J, due to rapid rise in freezing during tone presentation. Taken together, these data show that impaired fear extinction is a phenotypic feature common across 129 substrains, and provide preliminary evidence that impaired fear extinction in 129S1 may reflect a pro-fear incubation-like process. [source]

Strain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse Strains

ALCOHOLISM, Issue 8 2010
Noah R. Gubner
Background:, High levels of impulsivity have been associated with a number of substance abuse disorders including alcohol abuse. Research has not yet revealed whether these high levels predate the development of alcohol abuse. Methods:, The current study examined impulsivity in 15 inbred strains of mice (A/HeJ, AKR/J, BALB/cJ, C3H/HeJ, C57BL/6J, C57L/J, C58/J, CBA/J, DBA/1J, DBA/2J, NZB/B1NJ, PL/J, SJL/J, SWR/J, and 129P3/J) using a Go/No-go task, which was designed to measure a subject's ability to inhibit a behavior. Numerous aspects of response to ethanol and other drugs of abuse have been examined in these strains. Results:, There were significant strain differences in the number of responses made during the No-go signal (false alarms) and the extent to which strains responded differentially during the Go and No-go signals (d,). The rate of responding prior to the cue did not differ among strains, although there was a statistically significant correlation between false alarms and precue responding that was not related to basal activity level. Interstrain correlations suggested that false alarms and rate of responding were associated with strain differences in ethanol-related traits from the published literature. Conclusions:, The results of this study do support a link between innate level of impulsivity and response to ethanol and are consistent with a genetic basis for some measures of behavioral inhibition. [source]

Kinetic Enzymatic Resolution of Cyclopropane Derivatives

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 12 2003
Jörg Pietruszka
Abstract The kinetic enzymatic resolution of various cyclopropane derivatives was systematically investigated. The study focused on synthetically useful cyclopropylmethanols (e.g., 18a/j or 19a/j) as well as some rarely investigated cyclopropanols (e.g., 24/25 or 27). The combination of enantioselective catalytic or diastereoselective synthesis of enantiomerically enriched compounds with enzymatic approaches ultimately led to the most convenient route to enantiomerically pure starting materials. Again, this was especially proven for the synthesis of cyclopropanols 18a/j and 19a/j. Key to the successful investigation was to rigorously establish an analytical tool for the analysis of enantiomeric composition of reaction mixtures. [source]

Dissemination of a Sjögren's syndrome,associated extranodal marginal-zone B cell lymphoma: Circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements

ARTHRITIS & RHEUMATISM, Issue 1 2006
A. Hansen
Objective Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. Methods Histopathologic and Ig heavy- and light-chain variable-region gene (VH/L) analyses were performed in sequential tissue samples from a patient with primary Sjögren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. Results This MZL expressed a CD20+,CD27+,sIgM/,+,IgD,,CD5,,CD10,,Bcl-6,,CD23,,p53,,p21,,MDM2, phenotype and mutated VH1,69/D2,21/JH4,,V,A27/J,2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with VH3,07/D3,22/JH3b,V,3L/J,2/3 and VH3,64/D3,03/JH2,V,A19/J,2 rearrangements, respectively) were also detected in the parotid glands and blood, and 1 of these (clone 2) was also detected in the lymph nodes. Ig VH/L analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. Conclusion These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS,associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) Ig VH/L mutations. [source]

The Langerhans' cell-like cell lines XS52 and XS106 express mRNA for ciliary neurotrophic factor and neurotrophic factor 4/5

EXPERIMENTAL DERMATOLOGY, Issue 9 2004
K. Seiffert
Neurotrophins are responsible for the survival and outgrowth of nerves within the peripheral and central nervous systems. These factors include brain-derived neurotrophic factor (BDNF), CNTF, NT 3, and NT4/5. We have previously shown that LCs lie in close proximity to nerves and that several neuropeptides regulate LC function, implying that nerves send regulatory signals to LCs. To evaluate the possibility that LC signal nerves by release of neurotrophins, we examined LC expression of neurotrophins by RT-PCR. To eliminate the possibility of contaminating keratinocytes in highly enriched LC preparations, we utilized the LC-like cell lines XS52 (BALB/c derived) and XS106 (A/J derived) for initial experiments. The RNA obtained was digested with DNase to ensure complete absence of genomic DNA. Several independent RT-PCRs revealed expression of bands of the expected size for CTNF and NT4/5, but not for BDNF and NT3 in XS106 and XS52 cells. In contrast, the transformed keratinocyte cell line PAM212 expressed BDNF, as well as CTNF and NT4/5. Preliminary experiments with purified LC confirm the expression of CTNF and NT4/5 and also show the expression of BDNF. However, we cannot be sure that BDNF expression is not due to keratinocyte contamination. We conclude that LCs may regulate nerve cells by the release of neurotrophic factors. [source]

STAT1 and STAT3 ,/, splice form activation predicts host responses in mouse hepatitis virus type 3 infection

JOURNAL OF MEDICAL VIROLOGY, Issue 3 2003
Qin Ning
Abstract Signal transducer and activator of transcription 1, (STAT1 ,) is reported to be essential for IFN-, and IFN-, regulated gene expression, while STAT1 ,, an alternate splice-form, mediates only IFN-,-dependent gene expression. STAT3 , and STAT3 , splice forms are also differentially activated in response to cytokines including IL-6 and IL-10. The aim of this study was to investigate whether the STAT activation will predict the host immune response to viral infection and possibly a therapeutic target for the treatment of viral infection. Mouse hepatitis virus type 3 (MHV-3) resistant strain (A/J) and sensitive mouse strains (BalB/cJ) were infected intraperitoneally (i.p.) with 100 plaque form units (pfu) of MHV-3. The mice were sacrificed at the indicated times, and livers and spleens were immediately frozen in liquid nitrogen. Nuclear extracts proteins were detected by immunoblotting. STAT1 and STAT3 activation in spleen increased 24 to 72 hr following MHV-3 infections in both sensitive and resistant mouse strains. However, over this time period, the ratio of activated , to , splice-form for STAT1 and STAT3 increased above 1.0 in resistant A/J mice, while the ratio fell to <0.3 in MHV-3 sensitive Balb/cJ and C3H/HeJ strains. Activated STAT1 ,/, and STAT3 ,/, ratio in liver were similar in resistant and sensitive mouse strains. Treatment of sensitive Balb/cJ mice with neutralizing anti-TGF-, antibody could increase the STAT1 ,/, ratio to <1.0 in spleens, predicting enhanced rates of survival. These results suggested that ratio of activated STAT1 ,/, and STAT3 ,/, in mixed leukocytes from spleen predict the outcome to MHV-3 infection, and may be an important marker and therapeutic target for modification of host immune response to virus infection. J. Med. Virol. 69:306,312, 2003. © 2003 Wiley-Liss, Inc. [source]

A Polymorphism in the ,4 Nicotinic Receptor Gene (Chrna4) Modulates Enhancement of Nicotinic Receptor Function by Ethanol

ALCOHOLISM, Issue 5 2003
Christopher M. Butt
Background: Several studies indicate that ethanol enhances the activity of ,4,2 nicotinic acetylcholine receptors (nAChR). Our laboratory has identified a polymorphism in the ,4 gene that results in the substitution of an alanine (A) for threonine (T) at amino acid position 529 in the second intracellular loop of the ,4 protein. Mouse strains expressing the A variant have, in general, greater nAChR-mediated 86Rb+ efflux in response to nicotine than strains with the T variant. However, the possibility of the polymorphism modulating the effects of ethanol on the 86Rb+ efflux response has not been investigated. Methods: We have used the 86Rb+ efflux method to study the acute effects of ethanol on the function of the ,4,2 nAChR in the thalamus in six different mouse strains. Experiments were also performed on tissue samples taken from F2 intercross animals. The F2 animals were derived from A/J mice crossed with a substrain of C57BL/6J mice that carried a null mutation for the gene encoding the ,2 nAChR subunit. Results: In strains carrying the A polymorphism (A/J, AKR/J, C3H/Ibg), coapplication of ethanol (10,100 mM) with nicotine (0.03,300 ,M) increased maximal ion flux when compared with nicotine alone with no effect on agonist potency. In contrast, ethanol had little effect on the nicotine concentration-response curve in tissue prepared from strains carrying the T polymorphism (Balb/Ibg, C57BL/6J, C58/J). Experiments with the F2 hybrids demonstrated that one copy of the A polymorphism was sufficient to produce a significant enhancement of nAChR function by ethanol (50 mM) in animals that were also ,2 +/+. Ethanol had no effect on nicotine concentration-response curves in T/T ,2 +/+ animals. Conclusions: The results suggest that the A/T polymorphism influences the initial sensitivity of the ,4,2 nAChR to ethanol. [source]

Heritability of the Blood Pressure Response to Acute Ethanol Exposure in Five Inbred Strains of Mice

ALCOHOLISM, Issue 10 2000
Daniel C. Hatton
Background: Chronic alcohol consumption is a major risk factor for hypertension. There is evidence in humans that the susceptibility to alcohol-related hypertension may vary based on genotype. As a first step in investigating the genetic basis for alcohol-related hypertension, the current study was designed to assess the heritability of the blood pressure response to acute ethanol exposure by using AKR/J (AK), C57BL/6J (B6), DBA/2J (D2), Balb/cJ (Balb), and A/J (A) mice. Methods: Mean arterial pressure (MAP) was recorded continuously for 24 hr in freely moving mice from an indwelling femoral catheter before we tested the effects of saline or ethanol (2 g/kg ip) on blood pressure. Results: Relative to saline, ethanol caused a pressor response that peaked within 10 min, followed by a decline in MAP. Strain A mice had a significantly greater pressor response to ethanol than other strains and did not show a decline in MAP below baseline. All other strains showed a progressive fall in blood pressure below baseline across the 60 min measurement interval. Heritability was estimated to be 0.62 for the pressor response and 0.64 for the maximal depressor response. Repeated doses of ethanol at 1 hr intervals in A and B6 mice (0,2,1.5,1.5,1.5 g/kg ip) resulted in a dose-dependent increase in MAP in A mice for the first three doses and a dose-dependent decrease in MAP in B6 mice that was independent of blood ethanol concentrations. Conclusion: The results indicate that there is a significant genetic component to the acute blood pressure response to ethanol. [source]

Dissemination of a Sjögren's syndrome,associated extranodal marginal-zone B cell lymphoma: Circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements

Strain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse Strains

A Polymorphism in the ,4 Nicotinic Receptor Gene (Chrna4) Modulates Enhancement of Nicotinic Receptor Function by Ethanol

Heritability of the Blood Pressure Response to Acute Ethanol Exposure in Five Inbred Strains of Mice

Involvement of Transcription Factor HNF3, in the Effect of o -Aminoazotoluene on Glucocorticoid Induction of Tyrosine Aminotransferase in Mice Sensitive to its Hepatocarcinogenic Action

MOLECULAR CARCINOGENESIS, Issue 1 2001
Konstantin Y. Kropachev
Abstract In the rodent liver, hepatocarcinogens inhibit the glucocorticoid induction of several liver-specific genes, including tyrosine aminotransferase (TAT). A distinct positive correlation exists in mice between the extent of inhibition of TAT induction after acute administration of o -aminoazotoluene (OAT) and the frequency of liver tumors after chronic exposure to the carcinogen. To elucidate the mechanism of the carcinogenic action, the effects of OAT on the DNA-binding activity of several transcription factors participating in the glucocorticoid regulation of TAT gene expression were studied. The experimental inbred male mice were sensitive (A/He and SWR/J, tumor induction frequency of 75,100%, TAT induction inhibition of 35,50%) and resistant (CC57BR/Mv and AKR/J, 0,6% and 10,15%, respectively) to OAT. Gel retardation experiments showed that hepatocyte nuclear factor 3 (HNF3), DNA-binding activity was strongly reduced in nuclear extracts from the livers of OAT-treated A/He and SWR/J mice but only slightly reduced in CC57Br/Mv and AKR/J mice. The DNA-binding activities of Ets, AP1 family members, and GME binding proteins were unaffected. HNF3, DNA-binding activity was reduced by 1 h after OAT administration and remained low for 1 mo, as did inhibition of TAT induction in the liver. These results suggested that the inhibitory effect of OAT on the glucocorticoid induction of TAT is mediated by reduced HNF3, DNA-binding activity. © 2001 Wiley-Liss, Inc. [source]

Performance deficit of ,7 nicotinic receptor knockout mice in a delayed matching-to-place task suggests a mild impairment of working/episodic-like memory

GENES, BRAIN AND BEHAVIOR, Issue 6 2006
C. Fernandes
Patients with schizophrenia exhibit deficits in a range of cognitive functions, particularly working and episodic memory, which are thought to be core features of the disorder. Memory dysfunction in schizophrenia is familial and thus a promising endophenotype for genetic studies. Both human and animal studies suggest a role for the neural nicotinic acid receptor family in cognition and specifically the ,7-receptor subunit in schizophrenia and its endophenotypes. Consequently, we tested mice lacking the ,7 subunit of the neural nicotinic receptor (B6.129S7-Chrna7tm1Bay/J) in the delayed matching-to-place (DMP) task of the Morris water maze, a measure of working/episodic memory akin to human episodic memory. We report that a minor impairment in ,7 knockout mice was observed in the DMP task, with knockout mice taking longer to find the hidden platform than their wildtype controls. This suggests a role for the ,7 subunit in working/episodic memory and a potential role for the ,7 neural nicotinic receptor gene (CHRNA7) in schizophrenia and its endophenotypes. [source]

ORIGINAL RESEARCH,BASIC SCIENCE: Erectile Dysfunction in Hypercholesterolemic Atherosclerotic Apolipoprotein E Knockout Mice

THE JOURNAL OF SEXUAL MEDICINE, Issue 4 2006
Delphine Behr-Roussel PharmD
ABSTRACT Introduction., Erectile dysfunction (ED) and cardiovascular diseases share the same risk factors. Although the use of hypercholesterolemic rabbit models has proven to be useful to illustrate the link between ED and hypercholesterolemia, the cost of daily maintenance of the animals and necessity for important amounts of drug have limited their use. Aim., We aimed to develop a new model of atherosclerosis-associated ED in a well-known experimental model of atherosclerosis, the apolipoprotein E knockout (ApoE KO) mouse. Methods., Erectile function was evaluated by recording frequency-dependent increases in intracavernous pressure following electrical stimulation of the cavernous nerve in 26-, 32-, and 38-week-old ApoE KO mice fed a Western-type diet and age-matched C57BL6/J anesthetized mice. Atherosclerotic lesions were evaluated by planimetry in oil red O-stained aortas. Results., We found that in contrast to C57BL6/J mice, ApoE mice displayed atherosclerotic lesions covering 22% of the aortic luminal surface at 26 weeks of age and increasing to 27% and 35% at 32 weeks and 38 weeks of age, respectively. The amplitude of erectile responses to electrical stimulation of the cavernous nerve was markedly impaired in 26-week-old ApoE KO mice as compared with age-matched C57BL6/J mice. Impairment in erectile function persisted in ApoE KO mice 32 and 38 weeks of age. Conclusions., The ApoE KO mouse, a well-characterized model to study disorders associated with hypercholesterolemia and atherosclerosis in cardiovascular research, could therefore be suitable for investigation of disease-modifying effects of new therapeutic strategies aiming to target both atherosclerosis and ED. Behr-Roussel D, Darblade B, Oudot A, Compagnie S, Bernabé J, Alexandre L, and Giuliano F. Erectile dysfunction in hypercholesterolemic atherosclerotic apolipoprotein E knockout mice. J Sex Med 2006;3:596,603. [source]

Alcohol, Cocaine, and Brain Stimulation-Reward in C57Bl6/J and DBA2/J Mice

ALCOHOLISM, Issue 1 2010
Eric W. Fish
Background:, Pleasure and reward are critical features of alcohol drinking that are difficult to measure in animal studies. Intracranial self-stimulation (ICSS) is a behavioral method for studying the effects of drugs directly on the neural circuitry that underlies brain reward. These experiments had 2 objectives: first, to establish the effects of alcohol on ICSS responding in the C57Bl6/J (C57) and DBA2/J (DBA) mouse strains; and second, to compare these effects to those of the psychostimulant cocaine. Methods:, Male C57 and DBA mice were implanted with unipolar stimulating electrodes in the lateral hypothalamus and conditioned to spin a wheel for reinforcement by the delivery of rewarding electrical stimulation (i.e., brain stimulation-reward or BSR). Using the curve-shift method, the BSR threshold (,0) was determined immediately before and after oral gavage with alcohol (0.3, 0.6, 1.0, 1.7 g/kg) or water. Blood alcohol concentration (BAC) was measured to determine the influence of alcohol metabolism on BSR threshold. Separately, mice were administered cocaine (1.0, 3.0, 10.0, 30.0 mg/kg) or saline intraperitoneally. Results:, In C57 mice, the 0.6 g/kg dose of alcohol lowered BSR thresholds by about 20%, during the rising (up to 40 mg/dl), but not falling, phase of BAC. When given to the DBA mice, alcohol lowered BSR thresholds over the entire dose range; the largest reduction was by about 50%. Cocaine lowered BSR thresholds in both strains. However, cocaine was more potent in DBA mice than in C57 mice as revealed by a leftward shift in the cocaine dose,response curve. For both alcohol and cocaine, effects on BSR threshold were dissociable from effects on operant response rates. Conclusions:, In C57 and DBA mice, reductions in BSR threshold reflect the ability of alcohol to potentiate the neural mechanisms of brain reward. The DBA mice are more sensitive to the reward-potentiating effects of both alcohol and cocaine, suggesting that there are mouse strain differences in the neural mechanisms of brain reward that can be measured with the ICSS technique. [source]

Cholangiocyte bile salt transporters in cholesterol gallstone,susceptible and resistant inbred mouse strains

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 10 2008
Julia J Liu
Abstract Background and Aim:, We investigated the dietary and gender influences on the expression and functionality of cholangiocyte bile salt transporters and development of biliary hyperplasia in cholesterol gallstone-susceptible C57L/J and resistant AKR/J mice. Methods:, C57L and AKR mice were fed chow, a lithogenic diet, or a cholic acid-containing diet for 14 days. Expression of cholangiocyte bile salt transporter proteins ASBT (SLC10A2), ILBP (FABP6), and MRP3 (ABCC3) were studied by Western blot analysis. Taurocholate uptake studies were performed using microperfusion of isolated bile duct units. The pre- and post-perfusion taurocholate concentrations were analyzed by high performance liquid chromatography. Biliary proliferation in liver sections was scored. Results:, The lithogenic diet induced ductular proliferation in C57L mice. On chow, SLC10A2 and ABCC3 were overexpressed in male and female C57L compared to AKR mice. A lithogenic diet reduced the expressions of FABP6 in both male and female C57L mice, SLC10A2 in female C57L mice, and ABCC3 in male C57L mice. These alterations in transporter expressions were not associated with changes in taurocholate uptake. The lithogenic diet induced biliary hyperplasia and reduced bile salt transporter expressions in C57L mice. Conclusions:, Although bile salt uptake was not increased in the bile duct unit, we speculate that the biliary hyperplasia on the lithogenic diet may lead to an increase in intrahepatic bile salt recycling during cholesterol cholelithogenesis. [source]

Strain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse Strains

A Polymorphism in the ,4 Nicotinic Receptor Gene (Chrna4) Modulates Enhancement of Nicotinic Receptor Function by Ethanol

Strain Differences in Behavioral Inhibition in a Go/No-go Task Demonstrated Using 15 Inbred Mouse Strains

ORIGINAL ARTICLE: PD-1 but not CTLA-4 Blockage Abrogates the Protective Effect of Regulatory T Cells in a Pregnancy Murine Model

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 5 2009
Paul Ojiambo Wafula
Problem, Regulatory T cells (Treg) play an important role in fetal protection. They expand during normal pregnancy and protect paternal/fetal antigens from rejection by maternal effector cells. Accordingly, the transfer of Treg obtained from BALB/c-mated CBA/J females prevents abortion in DBA/2J-mated animals. The actual mechanism through which Treg mediate their protective effect is still inconclusive. Cytotoxic T lymphocyte antigen-4 (CTLA-4) and Programmed cell death 1 (PD-1) are some of known Treg-associated molecules; however, their role in Treg-mediated fetal protection in murine model has not been investigated. Method of study, Treg obtained from normal pregnant animals (NP; CBA/J × BALB/c) on day 14 were adoptively transferred into abortion-prone mice (AP; CBA/J × DBA/2J) intravenously on day 2 of pregnancy. An amount of 250 ,g of either anti-PD-1 or anti-CTLA-4 mAb were injected intraperitoneally on days 0, 3, 6 and 9 of pregnancy. Controls received Treg + IgG or Treg + PBS. NP or AP treated with PBS served as additional controls. Results, Blocking PD-1 abrogated the protective effect of Treg, resulting in a higher median abortion rate in comparison with the Treg/isotype-treated control while CTLA-4 blockage did not interfere with the protective effect of Treg. This was associated with a diminished number of vascular endothelial growth factor-A+ cells, previously reported as stimulators of lymphocyte extravasation in preterm labor. Conclusion, Our data suggest PD-1 as an important mediator in Treg-induced fetal protection in the CBA/J × DBA/2J murine model. [source]

ORIGINAL ARTICLE: IL-6 as a Regulatory Factor of the Humoral Response During Pregnancy

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2008
Valeria Dubinsky
Problem, Regulatory factors seem to be essential to achieve transition from implantation window to placental vascularization. A novel function of interleukin (IL)-6 in the promotion of Th2 differentiation and inhibition of Th1 polarization has been demonstrated. Considering that Th2 response promotes antibody synthesis, we postulate that IL-6 could be modulating the quality of this response during pregnancy by increasing the proportion of blocking asymmetric antibodies. Method of study, We investigated expression of blocking-asymmetric-IgG during pregnancy of CBA/J × DBA/2 abortion model treated with IL-6, with regards to CBA/J × BALB/c. We also determined asymmetric-IgG production in IL-6-deficient pregnant mice. Results, We found that IL-6 treatment increased asymmetric-IgG in multiparous placentas from abortion combination whereas diminished abortion rate. Moreover, asymmetric-IgG proportion was diminished in sera from IL-6-deficient pregnant mice. Conclusion, Modulation of asymmetric antibody synthesis could be another mechanism implicated in the beneficial effect of IL-6 in prevention of murine recurrent abortion. [source]

Ovariectomy-Induced Bone Loss Varies Among Inbred Strains of Mice,

JOURNAL OF BONE AND MINERAL RESEARCH, Issue 7 2005
Mary L Bouxsein PhD
Abstract There is a subset of women who experience particularly rapid bone loss during and after the menopause. However, the factors that lead to this enhanced bone loss remain obscure. We show that patterns of bone loss after ovariectomy vary among inbred strains of mice, providing evidence that there may be genetic regulation of bone loss induced by estrogen deficiency. Introduction: Both low BMD and increased rate of bone loss are risk factors for fracture. Bone loss during and after the menopause is influenced by multiple hormonal factors. However, specific determinants of the rate of bone loss are poorly understood, although it has been suggested that genetic factors may play a role. We tested whether genetic factors may modulate bone loss subsequent to estrogen deficiency by comparing the skeletal response to ovariectomy in inbred strains of mice. Materials and Methods: Four-month-old mice from five inbred mouse strains (C3H/HeJ, BALB/cByJ, CAST/EiJ, DBA2/J, and C57BL/6J) underwent ovariectomy (OVX) or sham-OVX surgery (n = 6-9/group). After 1 month, mice were killed, and ,CT was used to compare cortical and trabecular bone response to OVX. Results: The effect of OVX on trabecular bone varied with mouse strain and skeletal site. Vertebral trabecular bone volume (BV/TV) declined after OVX in all strains (,15 to ,24%), except for C3H/HeJ. In contrast, at the proximal tibia, C3H/HeJ mice had a greater decline in trabecular BV/TV (,39%) than C57BL/6J (,18%), DBA2/J (,23%), and CAST/EiJ mice (,21%). OVX induced declines in cortical bone properties, but in contrast to trabecular bone, the effect of OVX did not vary by mouse strain. The extent of trabecular bone loss was greatest in those mice with highest trabecular BV/TV at baseline, whereas cortical bone loss was lowest among those with high cortical bone parameters at baseline. Conclusions: We found that the skeletal response to OVX varies in a site- and compartment-specific fashion among inbred mouse strains, providing support for the hypothesis that bone loss during and after the menopause is partly genetically regulated. [source]

Adolescent C57BL/6J (but not DBA/2J) Mice Consume Greater Amounts of Limited-Access Ethanol Compared to Adults and Display Continued Elevated Ethanol Intake into Adulthood

ALCOHOLISM, Issue 4 2010
Eileen M. Moore
Background:, Alcohol use is common during the adolescent period, a time at which a number of crucial neurobiological, hormonal, and behavioral changes occur (Spear, 2000). In order to more fully understand the complex interaction between alcohol use and these age-typical neurobiological changes, animal models must be utilized. Rodents experience a developmental period similar to that of adolescence. Although rat models have shown striking adolescent-specific differences in sensitivity to ethanol, little work has been done in mice despite the fact that the C57BL/6J (B6) and DBA2/J (D2) mice have been shown to markedly differ in ethanol preference drinking and exhibit widely different sensitivities to ethanol. Methods:, The current study examined ethanol intake in adolescent and adult B6 and D2 mice using a limited access alcohol exposure paradigm called Drinking in the Dark (DID). Additionally, the effect of adolescent (or adult) ethanol exposure on subsequent adult ethanol intake was examined by re-exposing the mice to the same paradigm once the adolescents reached adulthood. We hypothesized that adolescent (P25,45) mice would exhibit greater binge-like alcohol intake compared to adults (P60,80), and that B6 mice would exhibit greater binge-like alcohol intake compared to D2 mice. Moreover, we predicted that relative difference in binge-like alcohol intake between adolescents and adults would be greater in D2 mice. Results:, Adolescent B6 mice consumed more ethanol than adults in the DID model. There was no difference between adolescent and adult D2 mice. Conclusions:, This work adds to the literature suggesting that adolescents will consume more ethanol than adults and that this exposure can result in altered adult intake. However, this effect seems largely dependent upon genotype. Future work will continue to examine age-related differences in ethanol intake, preference, and sensitivity in inbred mouse strains. [source]

Alcohol, Cocaine, and Brain Stimulation-Reward in C57Bl6/J and DBA2/J Mice

Sleep Loss Induces Differential Response Related To Genotoxicity in Multiple Organs of Three Different Mice Strains

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010
Vanessa Kahan
Swiss, C57BL/6j and hairless (HRS/j) mice were submitted to PSD by the multiple platform technique for 72 hr, and DNA damage was evaluated. Statistically significant differences in DNA damage were found in blood cells of the Swiss mice strain when compared to negative controls. By contrast, no statistically significant differences were found in the C57BL/6j or hairless mice strains. With regard to the liver, extensive genotoxic effects were found in the Swiss strain. The hairless and C57BL/6j mice strains did not show any signs of genotoxocity in this organ. The same lack of effect was noted in kidney and heart cells of all strains evaluated. In conclusion, our results reveal that sleep deprivation exerted genetic damage in the form of DNA breakage in blood and liver cells of the Swiss mice strain only. This type of approach should be considered when studying noxious activities on genetic apparatus induced by sleep deprivation in mice since the Swiss strain is more suitable for this purpose. [source]

Maximum likelihood constrained deconvolution.

CONCEPTS IN MAGNETIC RESONANCE, Issue 2 2003
II: Application to experimental two-, three-dimensional NMR spectra
Abstract The maximum likelihood method (MLM) and related protocols were applied to the experimental 2-D nuclear Overhauser effect (NOE) spectrum of a 24-nucleotide RNA hairpin loop molecule. The output becomes more valuable when diagonal symmeterization is followed by MLM. This symmeterized maximum likelihood (SML) protocol restores the original spectral information with high fidelity by accurately partitioning components from overlapped peaks and provides substantial improvements in line shape and spectral resolution, in particular in the F1 dimension. These advantages lead to a simpler interpretation of the resonance frequencies, intensities, multiplet fine structure, and J -coupling values from a heavily overlapped peak region. This promises a more effective tool for peak picking, assignment, and integration. Also, application of MLM and related protocols to the 2-D NOE proton spectrum of a 24-mer RNA dramatically increases the number of NOE-based distance constraints that can be used for determination of its 3-D molecular structure. By application of 3-D MLM to a simple 3-D spectrum, the spectral resolution and signal-to-noise (S/N) ratio was greatly improved by effective line sharpening and reduction of cross-talk between planes. © 2003 Wiley Periodicals, Inc. Concepts Magn Reson 18A: 146,156, 2003 [source]

Comparison of Hospital Mortality With Intra-Aortic Balloon Counterpulsation Insertion Before vs After Primary Percutaneous Coronary Intervention for Cardiogenic Shock Complicating Acute Myocardial Infarction

CONGESTIVE HEART FAILURE, Issue 5 2010
Scott Harris DO
We hypothesized that the insertion of the IABP before primary PCI might result in better survival of patients with cardiogenic shock compared with postponing the insertion until after primary PCI. We, therefore, retrospectively studied 48 patients who had undergone primary PCI with IABP because of cardiogenic shock complicating acute myocardial infarction (26 patients received the IABP before and 22 patients after primary PCI). No significant differences were present in the baseline clinical characteristics between the 2 groups. The mean number of diseased vessels was greater in the group of patients treated with the IABP before primary PCI (2.8±0.5 vs 2.3±0.7, P=.012), but the difference in the number of treated vessels was not significant. The peak creatine kinase and creatine kinase-MB levels were lower in patients treated with the IABP before primary PCI (median, 1077; interquartile range, 438,2067 vs median, 3299; interquartile range, 695,6834; P=.047 and median, 95; interquartile range, 34,196 vs median, 192; interquartile range, 82,467; P=.048, respectively). In-hospital mortality and the overall incidence of major adverse cardiac and cerebrovascular events were significantly lower in the group of patients receiving the IABP before primary PCI (19% vs 59% and 23% vs 77%, P=.007 and P=.0004, respectively). Multivariate analysis identified renal failure (odds ratio, 15.2; 95% confidence interval, 3.13,73.66) and insertion of the IABP after PCI (odds ratio, 5.2; 95% confidence interval, 1.09,24.76) as the only independent predictors of in-hospital mortality. In conclusion, the results of the present study suggest that patients with cardiogenic shock complicating acute myocardial infarction who undergo primary PCI assisted by IABP have a more favorable in-hospital outcome and lower in-hospital mortality than patients who receive IABP after PCI. Abdel-Wahab M, Saad M, Kynast J, et al. Comparison of hospital mortality with intra-aortic balloon counterpulsation insertion before versus after primary percutaneous coronary intervention for cardiogenic shock complicating acute myocardial infarction. Am J Cardiol. 2010;105:967,971. [source]