scholarly journals Effects of Muclin (Dmbt1) deficiency on the gastrointestinal system

2008 ◽  
Vol 294 (3) ◽  
pp. G717-G727 ◽  
Author(s):  
Robert C. De Lisle ◽  
Weihong Xu ◽  
Bruce A. Roe ◽  
Donna Ziemer

The Dmbt1 gene encodes alternatively spliced glycoproteins that are either membrane-associated or secreted epithelial products. Functions proposed for Dmbt1 include it being a tumor suppressor, having roles in innate immune defense and inflammation, and being a Golgi-sorting receptor in the exocrine pancreas. The heavily sulfated membrane glycoprotein mucin-like glycoprotein (Muclin) is a Dmbt1 product that is strongly expressed in organs of the gastrointestinal (GI) system. To explore Muclin's functions in the GI system, the Dmbt1 gene was targeted to produce Muclin-deficient mice. Muclin-deficient mice have normal body weight gain and are fertile. The Muclin-deficient mice did not develop GI tumors, even when crossed with mice lacking the known tumor suppressor p53. When colitis was induced by dextran sulfate sodium, there was no significant difference in disease severity in Muclin-deficient mice. Also, when acute pancreatitis was induced with supraphysiological caerulein, there was no difference in disease severity in the Muclin-deficient mice. Exocrine pancreatic function was impaired, as measured by attenuated neurohormonal-stimulated amylase release from Muclin-deficient acinar cells. Also, by [35S]Met/Cys pulse-chase analysis, traffic of newly synthesized protein to the stimulus-releasable pool was significantly retarded in Muclin-deficient cells compared with wild type. Thus Muclin deficiency impairs trafficking of regulated proteins to a stimulus-releasable pool in the exocrine pancreas.

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Joshua Oakes ◽  
Susan Hamilton

FK506 Binding Proteins (FKBPs) are a family of cis-trans prolyl isomerases that bind rapamycin and FK506. FKBP12 and 12.6 interact with ryanodine receptors (RyR), homotetrameric transmembrane ion channels that regulate Ca2+ release from the sarcoplasmic reticulum (SR). FKBP12 interacts with RyR1 in skeletal muscle and FKBP12.6 interacts with RyR2 in cardiac muscle to regulate the Ca2+ leak properties of these channels. Recently it has been suggested that FKBP12 also plays a role in regulating RyR2 activity. Using mice with a cardiac specific deficiency in FKBP12, we analyzed the role of FKBP12 in cardiac function. We found that both male and female mice with a α-MyHC Cre/Lox mediated deficiency in FKBP12 in the heart (FKBP12 KD) developed a mild dilated cardiomyopathy, with enlarged left ventricular diameter both during systole and diastole, decreased ejection fraction and decreased fractional shortening. To elucidate the mechanism for these effects we assessed Ca2+ sparks in isolated cardiomyocytes. We found an increase in both Ca2+ spark frequency and spark amplitude in FKBP12 cardiac deficient mice without a change in spark duration. Despite a mild phenotype in adult mice, we found that approximately 25% of all pregnancies (26/106) in the FKBP12 deficient mice resulted in the mothers dying following the birth. Autopsies show that these cardiac specific FKBP12 deficient mice had increased heart weight and significantly dilated ventricles compared to female Cre mice. Our data suggest that a cardiac specific deficiency in FKBP12 leads to the development of pregnancy induced cardiomyopathy. Echocardiography on FKBP12 deficient mice one day after giving birth found that there was no significant difference in ejection fraction or fractional shortening compared to α-MyHC Cre control mice. FKBP12 deficient females, however, had larger hearts and 50% (2/4) displayed heart failure and died. In conclusion, we show that FKBP12 does indeed alter Ca2+ handling in the heart and that a loss of FKBP12 leads to the development of pregnancy induced cardiomyopathies in females.


1999 ◽  
Vol 30 (3) ◽  
pp. 191-195 ◽  
Author(s):  
Sayonara M.P. Assis ◽  
Rosa L.R. Mariano ◽  
Sami J. Michereff ◽  
Gil Silva ◽  
Elizabeth A.A. Maranhão

Twenty yeast isolates, obtained from cabbage phylloplane, were evaluated for antagonistic activity against Xanthomonas campestris pv. campestris, in field. Plants of cabbage cv. Midori were pulverized simultaneously with suspensions of antagonists and pathogen. After 10 days, plants were evaluated through percentage of foliar area with lesions. Percentage of disease severity reduction (DSR%) was also calculated. Yeast isolates LR32, LR42 and LR19 showed, respectively, 72, 75 and 79% of DSR. These antagonists were tested in seven different application periods in relation to pathogen inoculation (T1=4 d before; T2=simultaneously; T3=4 d after; T4=4 d before + simultaneously; T5=4 d after + simultaneously; T6=4 d before + 4 d after; T7=4 d before + simultaneously + 4 d after). The highest DSRs were showed by LR42 (71%), LR42 (67%), LR35 (69%) and LR19 (68%) in the treatments T7, T4, T5 and T6, which significantly differed from the others. The same yeast antagonists were also tested for black rot control using different cabbage cultivars (Fuyutoyo, Master-325, Matsukaze, Midori, Sekai I and Red Winner). The DSRs varied from 58 to 61%, and there was no significant difference among cultivars.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Mefkure Eraslan Sahin ◽  
Erdem Sahin ◽  
Yusuf Madendag ◽  
Ilknur Col Madendag ◽  
Ahter Tanay Tayyar ◽  
...  

Background. Primary dysmenorrhea, defined as painful menstrual cramps originating in the uterus without underlying pathology, is a gynecological disease that affects quality of life and school success. Our goal was to determine the effect of anterior uterocervical angle on primary dysmenorrhea and disease severity. Methods. A total of 200 virgin adolescents, 16 to 20 years of age, were included in the study. The Andersch and Milsom scale was used to determine dysmenorrhea severity. Those with pathologies causing secondary dysmenorrhea were excluded from the study. Study subjects were grouped based on severity of pain. Demographic characteristics and uterocervical ultrasonographic measurements were compared among groups. Results. Of the 200 participants enrolled in the study, 50 were healthy controls and 150 had primary dysmenorrhea. Those with primary dysmenorrhea had a significant family history of primary dysmenorrhea compared with controls (P<0.001). Age (P=0.668), body mass index (P=0.898), menarche age (P=0.915), and length of menstrual cycles (P=0.740) were similar in all groups. The uterine corpus longitudinal axis, uterine corpus transverse axis, and uterine cervix longitudinal axis were also similar (P=0.359, P=0.279, and P=0.369, resp.). The mean uterocervical angle was 146.8 ± 6.0 in controls and 143.3 ± 7.3 in those with mild pain with no significant difference between the groups. In those with moderate pain, the mean uterocervical angle was 121.2 ± 7.3 compared with 101 ± 9.2 in those with severe pain, which was a significant difference. Additionally, there was also a significant difference in the uterocervical angle among those with mild, moderate, and severe pain (P<0.001). Conclusion. Our results indicate that a narrower anterior uterocervical angle is associated with primary dysmenorrhea and disease severity.


2010 ◽  
Vol 78 (6) ◽  
pp. 2653-2666 ◽  
Author(s):  
Hideyuki Shiomi ◽  
Atsuhiro Masuda ◽  
Shin Nishiumi ◽  
Masayuki Nishida ◽  
Tetsuya Takagawa ◽  
...  

ABSTRACT Citrobacter rodentium, a murine model pathogen for enteropathogenic Escherichia coli, colonizes the surface of intestinal epithelial cells and causes mucosal inflammation. This bacterium is an ideal model for investigating pathogen-host immune interactions in the gut. It is well known that gene transcripts for Th1 cytokines are highly induced in colonic tissue from mice infected with C. rodentium. However, it remains to be seen whether the Th1 or Th2 cytokines produced by antigen-specific CD4+ T cells provide effective regulation of the host immune defense against C. rodentium infection. To investigate the antigen-specific immune responses, C. rodentium expressing ovalbumin (OVA-C. rodentium), a model antigen, was generated and used to define antigen-specific responses under gamma interferon (IFN-γ)-deficient or interleukin-4 (IL-4)-deficient conditions in vivo. The activation of antigen-specific CD4+ T cells and macrophage phagocytosis were evaluated in the presence of IFN-γ or IL-4 in vitro. IFN-γ-deficient mice exhibited a loss of body weight and a higher bacterial concentration in feces during OVA-C. rodentium infection than C57BL/6 (wild type) or IL-4-deficient mice. This occurred through the decreased efficiency of macrophage phagocytosis and the activation of antigen-specific CD4+ T cells. Furthermore, a deficiency in antigen-specific CD4+ T-cell-expressed IFN-γ led to a higher susceptibility to mucosal and gut-derived systemic OVA-C. rodentium infection. These results show that the IFN-γ produced by antigen-specific CD4+ T cells plays an important role in the defense against C. rodentium.


2001 ◽  
Vol 2 (2) ◽  
pp. 26-31
Author(s):  
Al Qudri

ABSTRACT. Tempe of soybean is fermented soybean with Rhizopus ologosporus fungus. From a result of researchers, it is the fact that tempe can increase valuable of nutrion and digest capacity and also produce antibiotic . Utilization of abtibiotic in chiken food as stimulus growth in not recommended because it can cause resistance a certain germ and it is presume there are antibiotic residu in egg and chiken meat. It is hope that the use of fermented soybean oil meal can increase nutrient value and digest capacity as well as produce antibiotic, so that it can get a better growth and over come a problem of using antibiotic in chiken food. The study was conducted to evaluate the effect of fermented soybean oil meal utilization in the ration on body weight gain, feed consumption, feed conversion and mortality. The study use 80 unsex day old chick broiler CP-707 and conducted at Poulty Laboratory Product Agriculture Faculty, Syiah Kuala University. Chiken were putting in 27 houses unit, each unit contain of four chiken. The design of experiment was Completely Randomized Design, four treatments and five replication. The treatments were ration contained 0%, 5%, 10% and 15% fermented soybean oil meal as replace the use of soybean oil meal. The protein and energy content of all dietary treatments were equally composed from six weeks investigation, were body weight gain, feed consumption, feed conversion and mortality. The result of the study indicated that up to 10% graded of fermented soybean oil meal in ration were significant difference influenced increase the body weight gain and decrease the feed conversion. The fermented soybeanoil meal) utilization more than 10% were significant difference decrease the body weight gain and increase the feed conversion. If the inclusion was increase the feed consumption would tendency decline. In this study there were no mortality in all treatment. In can be advised from this study that fermented soybean oil meal could be used in broiler ration or in all poulty ration.


Biomedicine ◽  
2021 ◽  
Vol 41 (3) ◽  
Author(s):  
Dhuha Karim

The mean age of AS patients was (35.0 ± 9.8) years.When the patients and control subjects were divided into different age groups (>40, 30-40, <30 years), the differences were not significantin terms of disease prevalence. The results also showed that the percentage of male patients is higher than that of females. There was no significant difference (P?0.05) between patients and controls in the distribution of males and females.Most of the patients had the disease for a period of 5 years or higher, with a disease severity of ? 2.1 and functional disability degree of I, II. The resultsshoweddifferent patterns of distribution for the three tested cytokines. A significant increase in the level of TNF-?, anon-significantincrease in the level of CXCL-8, and a significant decrease in the level of IL-10 were observed in the sera of patients with AS compared with the control.The patients also demonstrated significant decreases in the serum ALT and AST enzyme levels, hemoglobin (Hb) level, white blood cells (WBC) count, and erythrocyte sedimentation rate (ESR) (P?0.05).The percentage of HLA-B27-positive Iraqi patients was lower than that of the HLA-B27-negative patients. Some of these patterns were also exposed to changes related to some determinants in patients, which included age, sex, disease duration, disease severity, functional disability, and HLA-B27 positivity,along with association with clinical subtypes of AS.The area under the curve was determined for the parameters of ESR, IL-10, TNF-? and CXCL-8.The most significant factor was found to beESR, followed by IL-10, and then TNF-?, with the presence of significant differences, while there was no diagnostic significance for CXCL-8 ,which showed no significant difference (p?0.05).  


2008 ◽  
Vol 21 (4) ◽  
pp. 891-901 ◽  
Author(s):  
M.J. Fernandez-Cabezudo ◽  
S. Azimullah ◽  
S.M. Nurulain ◽  
M. Mechkarska ◽  
D.E. Lorke ◽  
...  

Paraoxon is the bioactive metabolite of the organophosphate pesticide parathion. Desulphuration of parathion by liver enzymes or sunlight results in the formation of paraoxon which inhibits acetylcholine esterase (AChE) activity. In the present study, we analyzed the effect of a 6-week, subchronic treatment with two different daily intraperitoneal doses (30 or 40 nmol) of paraoxon on the immune system of BALB/c mice. At a dose of 30 nmol/day, body weight of treated animals was unchanged compared to the controls. In contrast, the higher dose (40 nmol/day) induced a reduction in body growth, particularly in the first 3 weeks of treatment, peaking at week 2 when the saline group showed a 14.2-fold increase in body weight gain compared to paraoxon-treated animals. Moreover, mice treated with either dose of paraoxon had a >50% reduction in AChE activity during the first 3 weeks of treatment, but by the end of the treatment (week 6), AChE activity returned to normal. With regard to immunological parameters, there was no significant difference in either total spleen weight or in the ratios of various spleen cell populations between control and paraoxon-treated animals. Furthermore, no changes were observed in mitogen-induced cytokine secretion from splenocytes of paraoxon-treated mice. Finally, subchronic exposure to paraoxon did not alter mortality of mice exposed to a bacterial infection with Salmonella typhimurium. These data suggest that although subchronic exposure to paraoxon induced a transient inhibition in AChE activity, it had no demonstrable effect on the host immune system.


Author(s):  
Elham Nozari Mirarkolaei ◽  
Mahdi Gholami ◽  
Elham Rostami ◽  
Azita Aliakbarniya ◽  
Massoumeh Hotelchi ◽  
...  

Introduction: Body weight gain in children and teenagers is one of the major challenges that cause undesirable health outcomes. Simultaneously with the prevalence of overweight and obesity, children and adolescents are diagnosed with 25-hydroxyvitamin D (25(OH)D) deficiency in different sides of the world. The present study aimed to assess 25(OH)D status among Iranian volunteers aged 1-16 years and find the correlation between 25(OH)D status and body mass index (BMI) subjects.    Material and Methods: The total volunteers included 807 Iranian children aged 1 to 16 referred to the general and endocrinology clinics in Babol city, Mazandaran Province. A trained physician determined anthropometric characteristics. Serum levels of calcium (Ca), phosphate (P), creatinine (Cr), urea, thyroxine (T4), thyroid-stimulating hormone (TSH), and 25(OH)D were assessed in all children.      Results: 25.27% of the children were 25(OH)D deficient, and 59.1% were insufficient. There was no significant difference in serum 25(OH)D level between girls and boys (P=0.13). A significant negative correlation was found in serum 25(OH)D level with weight (P=0.000, r=-0.12), BMI (P=0.000, r=-0.13), and age (P=0.000, r=-0.13). Conclusion: These data displayed that 25(OH)D insufficiency is highly prevalent among children in the north of Iran. Serum 25(OH)D levels are affected by age and BMI value. Improving vitamin D deficiency helps to maintain the health of children and adolescents during this critical period.


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