8 results on '"von Huth, Sebastian"'
Search Results
2. No effect of deleted in malignant brain tumors 1 deficiency on chemotherapy induced murine intestinal mucositis.
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Nexoe, Anders B., Pedersen, Andreas A., von Huth, Sebastian, Sorensen, Grith L., Holmskov, Uffe, Jiang, Ping-Ping, Detlefsen, Sönke, Husby, Steffen, and Rathe, Mathias
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MUCOSITIS ,BRAIN tumors ,CHEMOTHERAPY complications ,NATURAL immunity ,GENE expression - Abstract
Mucositis is a serious adverse effect of chemotherapeutic treatment. During intestinal mucositis, the mucosal barrier is compromised, increasing the risk of severe infections. Mucositis necessitates dose reduction or pauses in treatment, which affect the outcome of the treatment. Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger protein with effects on innate immunity and epithelial regeneration. We have previously shown that jejunal DMBT1 expression is increased in piglets during chemotherapeutic treatment. We hypothesized that DMBT1 ameliorates doxorubicin-induced mucositis. Individually-caged Dmbt1
+/+ (WT) and Dmbt1−/− (KO) female mouse littermates received intraperitoneal injections of either doxorubicin or saline. They were euthanized after three (D3) or seven days (D7). Weight loss was monitored every day, and serum citrulline levels were measured at termination. Intestinal tissue was analyzed for the expression of DMBT1 and proinflammatory cytokines (IL-1β, IL-6, and TNF). Specimens from the small intestines and colon were scored for inflammation and epithelial and mucosal architecture changes. We detected no effect of DMBT1 on weight loss, serum citrulline levels, expression of proinflammatory cytokines, or histologic damage. We detected a significant increase in crypt depth in WT mice compared to that in KO mice on D3. In conclusion, DMBT1 does not affect doxorubicin-induced mucositis in mice. [ABSTRACT FROM AUTHOR]- Published
- 2021
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3. Conductance artery stiffness impairs atrio-ventriculo-arterial coupling before manifestation of arterial hypertension or left ventricular hypertrophic remodelling.
- Author
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Kyhl, Kasper, von Huth, Sebastian, Bojer, Annemie, Thomsen, Carsten, Engstrøm, Thomas, Vejlstrup, Niels, and Madsen, Per Lav
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ARTERIAL diseases ,HYPERTENSION ,LEFT ventricular hypertrophy ,MAGNETIC resonance imaging ,BLOOD pressure - Abstract
As part of normal ageing, conductance arteries lose their cushion function, left ventricle (LV) filling and also left atrial emptying are impaired. The relation between conductance artery stiffness and LV diastolic function is normally explained by arterial hypertension and LV hypertrophy as needed intermediaries. We examined whether age-related aortic stiffening may influence LV diastolic function in normal healthy subjects. Aortic distensibility and pulse wave velocity (PWV) were related to LV emptying and filling parameters and left atrial emptying parameters as determined by magnetic resonance imaging in 36 healthy young (< 35 years) and 16 healthy middle-aged and elderly (> 35 years) with normal arterial blood pressure and myocardial mass. In the overall cohort, total aorta PWV correlated to a decrease in LV peak-emptying volume (r = 0.43), LV peak-filling (r = 0.47), passive atrial emptying volume (r = 0.66), and an increase in active atrial emptying volume (r = 0.47) (all p < 0.001). PWV was correlated to passive atrial emptying volume even if only the > 35-year-old were considered (r = 0.53; p < 0.001). Total peripheral resistance demonstrated similar correlations as PWV, but in a regression analysis only the total aorta PWV was related to left atrial (LA) passive emptying volume. Via impaired ventriculo-arterial coupling, the increased aortic PWV seen with normal ageing hence affects atrio-ventricular coupling, before increased aortic PWV is associated with significantly increased arterial blood pressure or LV hypertrophic remodelling. Our findings reinforce the existence of atrio-ventriculo-arterial coupling and suggest aortic distensibility should be considered an early therapeutic target to avoid diastolic dysfunction of the LV. [ABSTRACT FROM AUTHOR]
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- 2021
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4. Intestinal protozoan infections shape fecal bacterial microbiota in children from Guinea-Bissau.
- Author
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von Huth, Sebastian, Thingholm, Louise B., Kofoed, Poul-Erik, Bang, Corinna, Rühlemann, Malte C., Franke, Andre, and Holmskov, Uffe
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PROTOZOAN diseases ,INTESTINAL infections ,GIARDIA lamblia ,HELMINTHS ,INTESTINAL parasites ,PARASITIC diseases ,HELMINTHIASIS ,NEUROCYSTICERCOSIS - Abstract
Intestinal parasitic infections, caused by helminths and protozoa, are globally distributed and major causes of worldwide morbidity. The gut microbiota may modulate parasite virulence and host response upon infection. The complex interplay between parasites and the gut microbiota is poorly understood, partly due to sampling difficulties in remote areas with high parasite burden. In a large study of children in Guinea-Bissau, we found high prevalence of intestinal parasites. By sequencing of the 16S rRNA genes of fecal samples stored on filter paper from a total of 1,204 children, we demonstrate that the bacterial microbiota is not significantly altered by helminth infections, whereas it is shaped by the presence of both pathogenic and nonpathogenic protozoa, including Entamoeba (E.) spp. and Giardia (G.) lamblia. Within-sample diversity remains largely unaffected, whereas overall community composition is significantly affected by infection with both nonpathogenic E. coli (R
2 = 0.0131, P = 0.0001) and Endolimax nana (R2 = 0.00902, P = 0.0001), and by pathogenic E. histolytica (R2 = 0.0164, P = 0.0001) and G. lamblia (R2 = 0.00676, P = 0.0001). Infections with multiple parasite species induces more pronounced shifts in microbiota community than mild ones. A total of 31 bacterial genera across all four major bacterial phyla were differentially abundant in protozoan infection as compared to noninfected individuals, including increased abundance of Prevotella, Campylobacter and two Clostridium clades, and decreased abundance of Collinsella, Lactobacillus, Ruminococcus, Veillonella and one Clostridium clade. In the present study, we demonstrate that the fecal bacterial microbiota is shaped by intestinal parasitic infection, with most pronounced associations for protozoan species. Our results provide insights into the interplay between the microbiota and intestinal parasites, which are valuable to understand infection biology and design further studies aimed at optimizing treatment strategies. Author summary: Infections with enteric parasites, including helminths and protozoa, are among the most common infections in poor countries. These infections continue to have enormous impact on both mortality and morbidity worldwide. Enteric parasites inhabit the gut of the infected host, but how infections with these parasites may change the composition of bacteria within the gut remains more or less unclear. Here, we explore how the bacterial composition in stool from children from Guinea-Bissau (Western Africa) is altered by infection with different enteric parasite species. We find that infections with multiple parasite species induces more pronounced changes in the bacterial composition, and that certain parasite species significantly changes the diversity of bacteria. Furthermore, we demonstrate that fecal samples stored at room temperature on filter papers for months can be used in field studies of gut bacteria composition. Our study provides new insights into the complex relationship between enteric parasites and fecal bacteria composition, and may pave the way for new treatment options and help explain why some people are more susceptible to infection compared to others. [ABSTRACT FROM AUTHOR]- Published
- 2021
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5. Immunohistochemical Localization of Deleted in Malignant Brain Tumors 1 in Normal Human Tissues.
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Bathum Nexoe, Anders, Pedersen, Andreas Arnholdt, von Huth, Sebastian, Detlefsen, Sönke, Hansen, Pernille Lund, and Holmskov, Uffe
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IMMUNOHISTOCHEMISTRY ,BRAIN tumors ,MESSENGER RNA ,GENE expression in mammals ,MUCOUS membranes - Abstract
Deleted in malignant brain tumors 1 (DMBT1) is part of the innate immune system and is expressed on mucosal surfaces in various tissues throughout the human body. However, to date, the localization of DMBT1 has not been investigated systematically and comprehensively in normal human tissues. In this study, we analyzed the mRNA expression of DMBT1 in human tissue by quantitative real-time PCR and examined its localization and distribution in the tissue by immunohistochemical staining using the monoclonal DMBT1 antibody HYB213-6. Anti-ovalbumin was used as an isotype control. The highest level of mRNA expression of DMBT1 was found in the small intestine, and the expression level was high throughout the luminal digestive tract. The expression of DMBT1 was especially high in the luminal digestive tract and salivary glands. The lowest expression level was found in the spleen. Immunohistochemical staining showed a high expression level of DMBT1 on mucosal surfaces throughout the body. There was a clear correlation between the mRNA expression and immunohistochemical expression of DMBT1 in the tissue. DMBT1 is strongly expressed on mucosal surfaces and in salivary glands [ABSTRACT FROM AUTHOR]
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- 2020
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6. Minor compositional alterations in faecal microbiota after five weeks and five months storage at room temperature on filter papers.
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von Huth, Sebastian, Thingholm, Louise Bruun, Bang, Corinna, Rühlemann, Malte C., Franke, Andre, and Holmskov, Uffe
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GUT microbiome ,BLOOD testing ,RIBOSOMAL RNA ,GENE expression ,BACTEROIDETES - Abstract
The gut microbiota is recognized as having major impact in health and disease. Sample storage is an important aspect to obtain reliable results. Mostly recommended is immediate freezing, however, this is not always feasible. Faecal occult blood test (FOBT) papers are an appealing solution in such situations, and most studies find these to be applicable, showing no major changes within 7 days storage at room temperature (RT). As fieldwork often requires RT storage for longer periods, evaluation of this is warranted. We performed 16S rRNA gene sequencing of 19 paired faecal samples immediately frozen or kept five weeks and five months at RT on FOBT papers. Alpha-diversity evaluation revealed no effect of FOBT storage, and evaluation of beta-diversity showed that host explained 65% of community variation, while storage method explained 5%. Evaluation of community dispersion and the Firmicutes/Bacteroidetes ratio revealed a larger effect of storage time for fresh-frozen samples. Single taxa evaluation (order-to-genus level) showed significant alterations of four (of 37) genera after five weeks and five genera after five months. When comparing the two timepoints, alterations were only detectable for fresh-frozen samples. Our findings reveal that long term storage on FOBT papers is an applicable approach for microbiota research. [ABSTRACT FROM AUTHOR]
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- 2019
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7. Immunohistochemical Localization of Fibrinogen C Domain Containing 1 on Epithelial and Mucosal Surfaces in Human Tissues.
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von Huth, Sebastian, Moeller, Jesper B., Schlosser, Anders, Marcussen, Niels, Nielsen, Ole, Nielsen, Vicki, Sorensen, Grith L., and Holmskov, Uffe
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IMMUNOHISTOCHEMISTRY ,FIBRINOGEN ,GASTROINTESTINAL system ,EPITHELIAL cells ,RESPIRATORY organs - Abstract
Fibrinogen C domain containing 1 (FIBCD1) is a transmembrane receptor that binds chitin and other acetylated compounds with high affinity. FIBCD1 has previously been shown to be present in the epithelium of the gastrointestinal tract. In the present study, we performed a detailed analysis of normally structured human tissues for the expression of FIBCD1 by quantitative PCR and immunohistochemistry. We find that FIBCD1 is expressed in epithelial cells derived from all three germ layers. Endodermal-derived epithelial cells throughout the gastrointestinal tract and the respiratory system showed high expression of FIBCD1 and also mesodermal-derived cells in the genitourinary system and ectodermal-derived epidermis and sebaceous glands cells expressed FIBCD1. In some columnar epithelial cells, for example, in the salivary gland and gall bladder, the FIBCD1 expression was clearly polarized with strong apical reaction, while other columnar cells, for example, in small and large intestine and in bronchi, the staining was equally strong apically and basolaterally. In keratinocytes in skin, tongue, and oral cavity, the FIBCD1 staining was granular. This expression pattern together with the known binding properties supports that FIBCD1 plays a role in innate immunity in the skin and at mucosal surfaces. [ABSTRACT FROM AUTHOR]
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- 2018
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8. Placental Growth during Normal Pregnancy - A Magnetic Resonance Imaging Study.
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Langhoff, Lasse, Grønbeck, Lene, von Huth, Sebastian, axelsson, anna, Jørgensen, Connie, Thomsen, Carsten, and Vejlstrup, Niels
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PLACENTA development ,PREGNANCY ,MAGNETIC resonance imaging ,BIRTH weight ,GESTATIONAL age ,PLACENTA physiology ,LABOR (Obstetrics) ,LONGITUDINAL method ,PLACENTA ,SECOND trimester of pregnancy ,THIRD trimester of pregnancy - Abstract
Objective: To investigate normal human placental growth longitudinally throughout the second and third trimesters using MRI.Methods: Twenty normal, first-time singleton pregnancies were scanned 7 times between the 14th and 38th week of gestation, at 4-week intervals, using MRI. Placental volumes were measured in both sagittal and transversal slices. All placentas were weighed after delivery to make a comparative study.Results: Sixteen of the 20 women had increasing placental volumes from the 14th to 38th week of gestation. The 6th and 7th scan showed that 4 women had placentas of the same size. The mean placental volume increases linearly from the 14th till the 38th week of gestation, with a constant mean growth rate of 29.97 ml/week. The median placental volume extrapolated to delivery was to 856 ml (range 602-1,050 ml). The median weight of the exsanguinated placenta after delivery was 640 g (range 500-787 g). All pregnancies were carried to term, resulting in the delivery of healthy infants with good correlation between placental size and birth weight (R = 0.56, p = 0.009).Conclusion: Placental growth was measured systematically in a longitudinal study through the second and third trimesters using MRI. MRI provides a safe and feasible method to measure placental growth. The mean placental growth was linear throughout the second and third trimesters. [ABSTRACT FROM AUTHOR]- Published
- 2017
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