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Multiple Organs (multiple + organ)
Terms modified by Multiple Organs Selected AbstractsSleep Loss Induces Differential Response Related To Genotoxicity in Multiple Organs of Three Different Mice StrainsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2010Vanessa 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] Dento-alveolar and maxillofacial injuries: a 5-year multi-center study.DENTAL TRAUMATOLOGY, Issue 1 2008Part 2: Severity, location These injuries may cause morbidity and demand meticulously planned treatment. Part 1 of this study focused on the incidence of general trauma injuries, as well as facial or dental trauma. The aim of part 2 is to evaluate the severity and location of the dento-alveolar and maxillofacial injuries over 5 years. A retrospective cohort study was conducted based on data from the Israel National Trauma Registry. Patients admitted and hospitalized due to trauma injuries during the years 2000,2004, totaled 111 010 in which 5886 (5.3%) were maxillofacial or dental injuries. Most of these injuries were traffic-related (54.5%), followed by events at home (18.7%). Facial injuries combined with injuries to other organs involved occurred in 3721 (63.2%) of the patients. Most minor injuries were noted when no other organs were involved, while severe injuries were more common when multiple organs were involved. More than 25% of facial injuries required surgery. Meticulous epidemiologic studies are needed to support the leading role, extent, and severity of maxillofacial trauma. [source] Fjx1: A notch-inducible secreted ligand with specific binding sites in developing mouse embryos and adult brainDEVELOPMENTAL DYNAMICS, Issue 3 2005Rebecca Rock Abstract The mouse fjx1 gene was identified as a homologue to the Drosophila gene four-jointed (fj). Fj encodes a transmembrane type II glycoprotein that is partially secreted. The gene was found to be a downstream target of the Notch signaling pathway in leg segmentation and planar cell polarity processes during eye development of Drosophila. Here, we show that fjx1 is not only conserved in vertebrates, but we also identified the murine fjx1 gene as a direct target of Notch signaling. In addition to the previously described expression of fjx1 in mouse brain, we show here that fjx1 is expressed in the peripheral nervous system, epithelial cells of multiple organs, and during limb development. The protein is processed and secreted as a presumptive ligand. Through the use of an fjx1-AP fusion protein, we could visualize fjx1 binding sites at complementary locations, supporting the notion that fjx1 may function as a novel signaling molecule. Developmental Dynamics 234:602,612, 2005. © 2005 Wiley-Liss, Inc. [source] Utility of cell blocks in the diagnosis of thyroid aspiratesDIAGNOSTIC CYTOPATHOLOGY, Issue 2 2006Niria Sanchez M.D. Abstract Cell blocks (CBs) are often prepared with fine-needle aspirates (FNAs) from multiple organs as an adjunct to smears in the diagnosis of aspirated lesions. However, the literature contains few reports on their utility with regard to specific organ sites. At our institution, CBs are made routinely on FNAs when there is sufficient material remaining after smear preparation, with thyroid representing the largest volume. The aim of this study was to determine the utility of CBs in the diagnosis of thyroid lesions. From January 2002 to April 2004, 546 thyroid FNAs were performed. Eighty-two (15%) cases, from 60 females and 20 males (age range, 17,88 yr; mean, 50 yr), had CBs and formed the basis of this study. Seventy-four (90%) of the cases were performed by the radiologist or the clinician and 8 (10%) by the pathologist, all of which had an immediate assessment for adequacy. One to 7 passes were performed with an average of 3/case. The needles were immediately rinsed in Hanks' Balanced Salt Solution after smear preparation. CBs were made on bloody specimens/those with tissue fragments. Cell-block slides were reviewed for the presence of cellular elements and classified into three categories: (1) contributory, (2) noncontributory, or (3) provides additional information. Of the 82 cases, 23 (28%) were neoplastic, 51 (62%) were nonneoplastic, and 8 (10%) were nondiagnostic. Fifteen of the neoplastic cases had confirmatory biopsies, 9 of which were papillary carcinoma. The overall cellularity of the CBs was low, varying from 0 to 2 follicular groups in the noncontributory CBs and 3 to 6 follicular groups or papillary formations in the contributory CBs. CBs were contributory in 25 (31%) cases: 5 neoplastic (1 follicular neoplasm, 3 papillary carcinoma, and 1 suspicious for papillary carcinoma), 18 nonneoplastic, and 2 nondiagnostic. CBs were noncontributory in 56 (68%) cases: 18 neoplastic (4 papillary carcinomas, 1 suspicious for papillary carcinoma, 4 Hürthle cell neoplasms, and 9 follicular neoplasms), 33 nonneoplastic, and 5 nondiagnostic. One case was categorized as provided additional information because the CB showed material that was not present on the slides; however, it was still nondiagnostic. In summary, CBs did not help in the majority of cases. They were contributory in only 25 (31%) of the 82 cases, and of the 23 neoplastic cases, only 5 (22%) CBs were contributory. The contribution of the CBs in the diagnosis of thyroid lesions was minimal because of the low cellularity. On-site assessment of specimen adequacy often results in fewer passes, thus contributing to the low cellularity present in cell-block preparations. Ancillary studies may require additional passes. Diagn. Cytopathol. 2006; 34:89,92. © 2006 Wiley-Liss, Inc. [source] DNA damage in mice treated with sulfur dioxide by inhalationENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3 2005Ziqiang Meng Abstract Sulfur dioxide (SO2) is a ubiquitous air pollutant produced by the burning of fossil fuels. In this study, single-cell gel electrophoresis (the Comet assay) was used to evaluate the DNA damage produced by inhalation exposure of mice to SO2. Male and female mice were housed in exposure chambers and treated with 14.00 ± 1.25, 28.00 ± 1.98, 56.00 ± 3.11, and 112.00 ± 3.69 mg/m3 SO2 for 6 hr/day for 7 days, while control groups were exposed to filtered air. Comet assays were performed on blood lymphocytes and cells from the brain, lung, liver, spleen, kidney, intestine, and testicles of the animals. SO2 caused significant, dose-dependent increases in DNA damage, as measured by Olive tail moment, in all the cell types analyzed from both sexes of mice. The results indicate that inhalation exposure to SO2 damages the DNA of multiple organs in addition to the lung, and suggests that this damage could result in mutation, cancer, and other diseases related to DNA damage. Further work will be required to understand the ultimate toxicological significance of this damage. These data also suggest that detecting DNA damage in blood lymphocytes, using the Comet assay, may serve as a useful tool for evaluating the impact of pulmonary SO2 exposure in human biomonitoring studies. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] Immunohistochemical localization of cytochrome P4501A induced by 3,3,,4,4,,5-pentachlorobiphenyl (PCB 126) in multiple organs of northern leopard frogs, Rana pipiensENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2001Yue-Wern Huang Abstract Monoclonal antibody 1 12,3(MA1 12,3)recognizesanepitopeexclusivetocytochromeP450sinsubfamily1A (CYP1A) from all vertebrates tested so far, including one amphibian species. In this study, we first tested the utility of MAb 1,12-3 for detection of presumed CYP1A proteins in hepatic microsomes of northern leopard frogs treated without or with 3,3,,4,4,,5-pentachlorobiphenyl (PCB 126). Statistical analysis showed that ethoxyresorufin- O -deethylase (EROD) activities and CYP1A equivalents in treated groups were significantly increased at doses >2.3 mg/kg compared with the control groups (p < 0.05), and the increases were maintained for at least four weeks. This result confirmed that MAb 1,12-3 can be used for detection of CYP1A in northern leopard frogs and indicated that CYP1A is the primary catalyst for EROD in this species. In a subsequent experiment, sections of organs of PCB 126-treated frogs were immunohistochemically stained with MAb 1,12-3 to identify localization of the CYP1A in different cell types. The CYP1A staining was seen prominently in hepatocytes and epithelium of nephronic duct, while capillaries close to gastric epithelium and submucosal vascular epithelium in both stomach and intestine exhibited moderate to strong staining. The CYP1A was immunodetected in coronary endothelium and the vascular endothelium of lung and gonad. In skin, mild staining was seen in epithelial cells of mucous glands and serous glands and in vascular endothelium, demonstrating induction of CYP1A in the dermal layer. [source] Impaired aortic elastic properties in patients with systemic sarcoidosisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2008I. Moyssakis Abstract Background, Systemic sarcoidosis (Sar) is a granulomatous disorder involving multiple organs. Widespread vascular involvement and microangiopathy are common in patients with Sar. In addition, subclinical cardiac involvement is increasingly recognized in patients with Sar. However, data on the effect of Sar on the elastic properties of the arteries and myocardial performance are limited. In this study we looked for differences in aortic distensibility (AoD) which is an index of aortic elasticity, and myocardial performance of the ventricles, between patients with Sar and healthy subjects. In addition, we examined potential associations between AoD and clinical, respiratory and echocardiographic findings in patients with Sar. Materials and methods, A total of 83 consecutive patients (26 male/57 female, mean age 51·1 ± 13·3 years) with Sar, without cardiac symptoms, were included. All patients underwent echocardiographic and respiratory evaluation including lung function tests. Additionally, 83 age- and sex-matched healthy subjects served as controls. AoD was determined non-invasively by ultrasonography. Results, AoD was lower in the Sar compared to the control group (2·29 ± 0·26 vs. 2·45 ± 0·20 ·10,6 cm2· dyn,1, P < 0·01), while left ventricular mass (LVM) was higher in the Sar group (221·3 ± 50·2 vs. 195·6 ± 31·3 g, P = 0·007). Furthermore, myocardial performance of both ventricles was impaired in the Sar group. Multivariate linear regression analysis in the total sample population demonstrated a significant and independent inverse relationship between AoD and the presence of Sar (P < 0·001). The same analysis in the Sar patients showed that AoD was associated significantly and independently with the stage of Sar, age, systolic blood pressure, LVM and myocardial performance of both ventricles. No significant relationship was found between AoD and disease duration, pulmonary artery pressure or lung function tests. Conclusions, Presence and severity of Sar are associated with reduced aortic distensibility, irrespective of the disease duration, pulmonary artery pressure and lung function. In addition, patients with Sar have increased LVM and impaired myocardial performance. [source] Exocrine pancreatic dysfunction in sepsisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2003B. Tribl Abstract Background Sepsis in critical illness is associated with the progressive failure of multiple organs. This study aims to establish a correlation between the severity of sepsis and exocrine pancreatic dysfunction. Materials and methods In a prospective cohort study pancreatic exocrine function was tested by means of a secretin-cholecystokinin test in 21 critically ill, mechanically ventilated patients with sepsis according to criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference Committee (ACCP/SCCM): 11 patients with shock and 10 patients without shock. Data were compared with seven healthy controls. Results The volume of duodenal fluid was not statistically different in the three groups. Sepsis patients without shock had significantly reduced content of amylase and chymotrypsin in duodenal juice compared with healthy controls (P < 0·01). Secretion of amylase, chymotrypsin, trypsin (P < 0·01 each) and bicarbonate in duodenal fluid (P < 0·05) was impaired in the septic shock patients when compared with the healthy controls. The content of trypsin was different between sepsis patients and septic shock patients (P < 0·05). Spearman correlation analysis was significant between the amylase secretion and the APACHE III and SOFA scores (P < 0·01). The SOFA score was also related to secretion of trypsin (P < 0·05). In patients on pressor therapy, use of norepinephrine was associated with a significant decrease in bicarbonate secretion (P < 0·05). Conclusions Sepsis is associated with secretory pancreatic dysfunction that is worse in septic shock than in sepsis without shock. Impaired exocrine function was significantly correlated to the APACHE III and SOFA scores. [source] Suppression of liver regeneration and hepatocyte proliferation in hepatocyte-targeted glypican 3 transgenic mice,HEPATOLOGY, Issue 3 2010Bowen Liu Glypican 3 (GPC3) belongs to a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. GPC3 is overexpressed in hepatocellular carcinoma. Loss-of-function mutations of GPC3 result in Simpson-Golabi-Behmel syndrome, an X-linked disorder characterized by overgrowth of multiple organs, including the liver. Our previous study showed that GPC3 plays a negative regulatory role in hepatocyte proliferation, and this effect may involve CD81, a cell membrane tetraspanin. To further investigate GPC3 in vivo, we engineered transgenic (TG) mice overexpressing GPC3 in the liver under the control of the albumin promoter. GPC3 TG mice with hepatocyte-targeted, overexpressed GPC3 developed normally in comparison with their nontransgenic littermates but had a suppressed rate of hepatocyte proliferation and liver regeneration after partial hepatectomy. Moreover, gene array analysis revealed a series of changes in the gene expression profiles in TG mice (both in normal mice and during liver regeneration). In unoperated GPC3 TG mice, there was overexpression of runt related transcription factor 3 (7.6-fold), CCAAT/enhancer binding protein alpha (2.5-fold), GABA A receptor (2.9-fold), and wingless-related MMTV integration site 7B (2.8-fold). There was down-regulation of insulin-like growth factor binding protein 1 (8.4-fold), Rab2 (5.6-fold), beta-catenin (1.7-fold), transforming growth factor beta type I (3.1-fold), nodal (1.8-fold), and yes-associated protein (1.4-fold). Changes after hepatectomy included decreased expression in several cell cycle,related genes. Conclusion: Our results indicate that in GPC3 TG mice, hepatocyte overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration and alters gene expression profiles, and potential cell cycle,related proteins and multiple other pathways are involved and affected. (HEPATOLOGY 2010;52:1060,1067) [source] Nonalcoholic fatty pancreas diseaseHPB, Issue 4 2007Abhishek Mathur Abstract Background. Obesity leads to fat infiltration of multiple organs including the heart, kidneys, and liver. Under conditions of oxidative stress, fat-derived cytokines are released locally and result in an inflammatory process and organ dysfunction. In the liver, fat infiltration has been termed nonalcoholic fatty liver disease, which may lead to nonalcoholic steatohepatitis. No data are available, however, on the influence of obesity on pancreatic fat and cytokines, and nonalcoholic fatty pancreas disease (NAFPD) has not been described. Therefore, we designed a study to determine whether obesity is associated with increased pancreatic fat and cytokines. Materials and methods. Thirty C57BL/6J lean control and 30 leptin-deficient obese female mice were fed a 15% fat diet for 4 weeks. At 12 weeks of age all animals underwent total pancreatectomy. Pancreata from each strain were pooled for measurement of a) wet and dry weight, b) histologic presence of fat, c) triglycerides, free fatty acids (FFAs), cholesterol, phospholipids, and total fat, and d) interleukin (IL)-1, and tumor necrosis factor-alpha (TNF-,). Data were analyzed by Student's t test and Fisher's exact test. Results. Pancreata from obese mice were heavier (p<0.05) and had more fat histologically (p<0.05). Pancreata from obese mice had more triglycerides, FFAs, cholesterol, and total fat (p<0.05). Triglycerides represented 11% of pancreatic fat in lean mice compared with 67% of pancreatic fat in obese mice (p<0.01). Cytokines IL-1, and TNF-, also were elevated in the pancreata of obese mice (p<0.05). Conclusions. These data suggest that obese mice have 1) heavier pancreata, 2) more pancreatic fat, especially triglycerides and FFAs, and 3) increased cytokines. We conclude that obesity leads to nonalcoholic fatty pancreatic disease. [source] Gnathostomiasis: Import from LaosJOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 5 2006Felix Hennies Creeping eruption; Gnathostomiasis; Wangenschwellung Summary Gnathostomiasis is a nematode infestation endemic in Southeast Asia, which can involve multiple organs including the liver, eyes, gastrointestinal tract and CNS. The most common manifestation is recurrent migratory subcutaneous swellings which can appear anywhere on the body and are accompanied by pruritus and systemic symptoms such as low-grade fever, loss of appetite and nausea. The diagnosis is based on the clinical picture, history of travel, peripheral blood eosinophilia and the determination of agent-specific antibody levels. The standard treatment is albendazole. We present a 37-year-old Laotian woman, who had lived in Germany for 17 years, but developed recurrent swelling of the cheek following a visit to Laos. Because of the typical clinical findings, the history of a visit to Laos, and the presence of specific anti- Gnathostoma antibodies on Western blot, the diagnosis of cutaneous gnathostomiasis was made. Zusammenfassung Die Gnathostomiasis ist eine hauptsächlich in Südost-Asien endemisch vorkommende Nematodenerkrankung, die zu einem Befall multipler Organe wie Leber, Auge, Gastrointestinaltrakt und zentralem Nervensystem führen kann. Am häufigsten kommt es jedoch zu rezidivierenden, wandernden, subkutanen Schwellungen, die am gesamten Körper auftreten können und häufig von Juckreiz und Allgemeinsymptomen wie leichtem Fieber, Appetitlosigkeit und Übelkeit begleitet werden. Die Diagnose wird anhand des klinischen Bildes, der Reiseanamnese, einer Bluteosinophilie sowie der Bestimmung Erreger-spezifischer Antikörper gestellt. Als medikamentöse Therapie hat sich das Anthelminthikum Albendazol bewährt. Vorgestellt wird eine 37-jährige, seit 17 Jahren in Deutschland lebende Patientin aus Laos, die seit einem Jahr nach Rückkehr von einem Besuch in ihrer alten Heimat unter rezidivierenden Wangenschwellungen litt. Anhand der typischen Klinik, der positiven Reiseanamnese sowie des Nachweises spezifischer Anti- Gnathostoma -Antikörper im Western-Blot wurde die Diagnose einer kutanen Gnathostomiasis gestellt. [source] Attenuation of TCDD-induced oxidative stress by 670 nm photobiomodulation in developmental chicken kidneyJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 4 2008Jinhwan Lim 2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD), a potent developmental teratogen inducing oxidative stress and sublethal changes in multiple organs, provokes developmental renal injuries. In this study, we investigated TCDD-induced biochemical changes and the therapeutic efficacy of photobiomodulation (670 nm; 4 J/cm2) on oxidative stress in chicken kidneys during development. Eggs were injected once prior to incubation with TCDD (2 pg/g or 200 pg/g) or sunflower oil vehicle control. Half of the eggs in each dose group were then treated with red light once per day through embryonic day 20 (E20). Upon hatching at E21, the kidneys were collected and assayed for glutathione peroxidase, glutathione reductase, catalase, superoxide dimutase, and glutathione- S -transferase activities, as well as reduced glutathione and ATP levels, and lipid peroxidation. TCDD exposure alone suppressed the activity of the antioxidant enzymes, increased lipid peroxidation, and depleted available ATP. The biochemical indicators of oxidative and energy stress in the kidney were reversed by daily phototherapy, restoring ATP and glutathione contents and increasing antioxidant enzyme activities to control levels. Photobiomodulation also normalized the level of lipid peroxidation increased by TCDD exposure. The results of this study suggest that 670 nm photobiomodulation may be useful as a noninvasive treatment for renal injury resulting from chemically induced cellular oxidative and energy stress. © 2008 Wiley Periodicals, Inc. J Biochem Mol Toxicol 22:230,239, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20233 [source] Effect of blood group on idiopathic thrombotic thrombocytopenic purpuraJOURNAL OF CLINICAL APHERESIS, Issue 4 2009Lara Zuberi Abstract Thrombotic thrombocytopenic purpura (TTP) is a condition caused by deficiency of ADAMTS13 resulting in accumulation of ultra large Von Willebrand factor multimers (ULVWF), leading to micro thrombi in multiple organs. The varying susceptibilities of blood group antigens to ADAMTS13 have been demonstrated. A and B antigens are protective of VWF; and VWF purified from blood group O individuals has been shown to be cleaved faster by ADAMTS13 compared to VWF from blood group AB individuals. We proposed that there may be a difference in the incidence of blood groups in TTP patients compared with the general population. We felt this to be important for a life-threatening disease with poorly understood epidemiology. We report a retrospective analysis of 74 patients presenting from 1993 to 2008 with idiopathic TTP. We studied the incidence across various blood groups and also estimated the recurrence and mortality in each group. The incidence of various blood groups were as follows: O 36%, A 36%, B 25%, and AB 2%, compared with expected frequencies in the Detroit area: O 44%, A 33% B 20%, and AB 3%. There was a trend of lower than expected frequency of blood group O. There were 24 recurrences and 14 deaths, uniform across blood groups. We hypothesized that there may be an association between blood groups and the risk of TTP; however the differences in our study were not statistically significant. Recurrence and disease specific mortality did not appear to be impacted by blood group. J. Clin. Apheresis 2009. © 2009 Wiley-Liss, Inc. [source] Ichthyophonus -induced cardiac damage: a mechanism for reduced swimming stamina in salmonidsJOURNAL OF FISH DISEASES, Issue 9 2006R Kocan Abstract Swimming stamina, measured as time-to-fatigue, was reduced by approximately two-thirds in rainbow trout experimentally infected with Ichthyophonus. Intensity of Ichthyophonus infection was most severe in cardiac muscle but multiple organs were infected to a lesser extent. The mean heart weight of infected fish was 40% greater than that of uninfected fish, the result of parasite biomass, infiltration of immune cells and fibrotic (granuloma) tissue surrounding the parasite. Diminished swimming stamina is hypothesized to be due to cardiac failure resulting from the combination of parasite-damaged heart muscle and low myocardial oxygen supply during sustained aerobic exercise. Loss of stamina in Ichthyophonus -infected salmonids could explain the poor performance previously reported for wild Chinook and sockeye salmon stocks during their spawning migration. [source] Autonomic skin responses in females with Fabry diseaseJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2009Anette T. Møller Abstract Fabry disease is a genetic lysosomal disorder with dysfunction of the lysosomal enzyme ,-galactosidase A causing accumulation of glycolipids in multiple organs including the nervous system and with neuropathy as a prominent manifestation. Neurological symptoms include pain and autonomic dysfunction. This study examined peripheral autonomic nerve function in 19 female patients with Fabry disease and 19 sex and age-matched controls by measuring (1) sweat production following acetylcholine challenge; (2) the sympathetically mediated vasoconstrictor responses to inspiratory gasp, stress, and the cold pressor test; and (3) cutaneous blood flow following capsaicin. The vasoconstrictor response to inspiratory gasp was increased in Fabry patients compared to controls (p = 0.03), while the response to cold and mental stress did not change. Female patients with Fabry disease had a reduced sweat response to iontophoresis of acetylcholine (p = 0.04) and a smaller capsaicin-induced flare compared to controls. These findings suggest that female patients both have an impaired C-fiber function and local abnormalities in blood vessels and sweat glands. [source] Recurrent hepatic lymphangiomatosis after orthotopic liver transplantationLIVER TRANSPLANTATION, Issue 11 2007Seong H. Ra Hepatic lymphangiomatosis is a rare disease characterized by an abnormal lymphatic proliferation involving the liver alone, liver and spleen, or multiple organs. Hepatic lymphangiomatosis becomes symptomatic secondary to compression or replacement of the normal parenchyma, which can lead to liver failure. Resection and orthotopic liver transplantation (OLT) can be used as treatment for this disease. We herein describe a 42-year-old female who had undergone successful OLT for hepatic lymphangiomatosis with recurrent disease detected 19 yr later in the transplanted liver. This is, to our knowledge, the first described case of recurrent hepatic lymphangiomatosis after OLT. In conclusion, we discuss the clinical, radiologic, pathologic, and immunohistochemical findings and review other reported cases of hepatic lymphangiomatosis that have undergone OLT. Liver Transpl 13:1593,1597, 2007. © 2007 AASLD. [source] Platelet Recruitment in the Murine Hepatic Microvasculature During Experimental Sepsis: Role of NeutrophilsMICROCIRCULATION, Issue 2 2006GEORG SINGER ABSTRACT Objectives: Sepsis is a major clinical problem that often results in the dysfunction or failure of multiple organs, including the liver. While inflammatory cell activation has been implicated as an early critical event in sepsis-induced liver dysfunction, there is growing evidence for the involvement of activated platelets in this pathologic process. Methods: Intravital microscopy was used in this study to assess the magnitude and time course of platelet adhesion in the liver microcirculation during experimental sepsis and to determine whether the platelet accumulation is linked to leukocyte infiltration. The adhesion of platelets and leukocytes in terminal hepatic venules (THV) and sinusoids was quantified at 2, 4, and 6 h after abdominal sepsis induced by cecal ligation and puncture (CLP). Results: While the rolling and firm adhesion of platelets and leukocytes in THV were not altered in the first 2 h after CLP, platelet recruitment was observed at 4 h and further elevated at 6 h after CLP. Leukocyte adhesion in THV exhibited a similar time course. A similar accumulation of blood cells in sinusoids was noted after CLP. This was accompanied by an increased number of nonperfused sinusoids. CLP-induced leukocyte and platelet recruitment in THV and sinusoids was attenuated in mice rendered neutropenic with anti-neutrophil serum. Conclusion: These findings indicate that sepsis is associated with a neutrophil-dependent recruitment of platelets in the liver microcirculation that impairs sinusoidal perfusion and may contribute to the liver dysfunction associated with sepsis. [source] Paraquat-induced Fanconi syndromeNEPHROLOGY, Issue 5 2005HYO W GIL SUMMARY: The ingestion of paraquat, a non-selective herbicide, can be fatal in humans. Paraquat is toxic to multiple organs, including the kidney, heart, gastrointestinal tract and central nervous system. Although paraquat has been established as one cause of acute tubular necrosis, Fanconi syndrome presenting as severe hypophosphataemia after paraquat intoxication has not been reported. Here, we report the case of a 44-year-old Korean woman who presented with generalized proximal tubular dysfunction including aminoaciduria, phosphaturia and glycosuria after paraquat intoxication. We found that severe hypophosphataemia induces deep drowsiness. Renal biopsy findings indicated the presence of acute tubular necrosis that may be reversible. [source] Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow upPATHOLOGY INTERNATIONAL, Issue 10 2009Masaaki Ichinoe Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management. [source] Systemic granulomatous necrotizing vasculitis in a MPO,ANCA-positive patientPATHOLOGY INTERNATIONAL, Issue 8 2004Atsushi Kurata We present a case of myeloperoxidase antineutrophil cytoplasmic antibody (MPO,ANCA)-associated vasculitis that demonstrated a systemic granulomatous lesion at autopsy. The patient initially showed anorexia, general malaise and anemia. Colon fiber was examined to detect the bleeding site, which revealed ischemic mucosal damage associated with venous fibrin thrombus. Because a high titer of MPO,ANCA was found, ANCA-associated vasculitis was suspected and the patient was started on steroid pulse therapy. However, anemia, renal failure and respiratory failure worsened and the patient died of sudden cardiac failure 2 days after the start of the therapy. An autopsy revealed systemic arteritis in multiple organs including the kidneys, liver, spleen, gastrointestinal system and genital organs that indicated fibrinoid necrosis accompanied by granulomatous reaction with multinucleated giant cells; the granulomatous reaction further extended along the splenic capsule. Glomerulonephritis and diffuse pulmonary damage, which are common in MPO,ANCA-associated vasculitis, were almost absent but parapleural fibrosis was present. The direct cause of death was presumed to be hemorrhagic shock due to rupture of an aneurysm in the gastric subserosa. As far as we know, this is the first case of a systemic granulomatous reaction in MPO,ANCA-positive vasculitis, although the cause of the granulomatous lesion is unknown. [source] Hypothetical pathophysiology of acute encephalopathy and encephalitis related to influenza virus infection and hypothermia therapyPEDIATRICS INTERNATIONAL, Issue 2 2000Shumpei Yokota AbstractBackground: To establish a treatment strategy for acute encephalopathy and encephalitis associated with influenza virus infection, the pathophysiology of the disease was investigated through manifestations and laboratory findings of patients. Patients and Methods: A child with central nervous system (CNS) complications during the course of influenza virus infection was analyzed in view of immunologic abnormalities. In addition, four children with acute encephalopathy and encephalitis were enrolled in the hypothermia treatment for the purpose of stabilizing the cytokine storm in the CNS. Results: The CNS symptoms preceded the systemic progression to the failure of multiple organs (MOF) and disseminated intravascular coagulopathy (DIC). The mild hypothermia suppressed the brain edema on computed tomography (CT) scanning and protected the brain from the subsequent irreversible neural cell damage. Conclusion: The replicated viruses at the nasopharyngeal epithelium may disrupt the olfactory mucosa and gain access to the brain via the olfactory nerve system. The direct virus,glial cell interaction or viral stimulation of the glial cells induces the production and accumulation of the pro-inflammatory cytokines, especially tumor necrosis factor (TNF)-,, in the CNS. The cytokine storm results in neural cell damage as well as the apoptosis of astrocytes, due to the TNF-,,induced mitochondrial respiratory failure. The disruption of the blood,brain barrier progresses to the systemic cytokine storm, resulting in DIC and MOF. Mild hypothermia appears promising in stabilizing the immune activation and the brain edema to protect the brain from ongoing functional, apoptotic neural and glial damage and the systemic expansion of the cytokine storm. [source] Sustained delivery of therapeutic concentrations of human clotting factor IX , a comparison of adenoviral and AAV vectors administered in uteroTHE JOURNAL OF GENE MEDICINE, Issue 1 2002Holm Schneider Abstract Background Prenatal somatic gene therapy has been considered for genetic disorders presenting with morbidity at birth. Haemophilia is associated with an increased risk of catastrophic perinatal bleeding complications such as intracranial haemorrhage, which could be prevented by gene transfer in utero. Prenatal gene therapy may be more promising than postnatal treatment, as the fetus may be more amenable to uptake and integration of therapeutic DNA and the immaturity of its immune system may permit life-long immune tolerance of the transgenic protein, thus avoiding the dominant problem in haemophilia treatment, the formation of inhibitory antibodies. Methods Adenovirus serotype 5-derived or AAV serotype 2-derived vectors carrying human clotting factor IX (hfIX) cDNA or a reporter gene were administered intramuscularly, intraperitoneally or intravascularly to late-gestation mouse fetuses. Both vector types were evaluated with respect to the kinetics of hfIX delivery to the systemic circulation and possible immune responses against the vector or the transgene product. Results Mice treated in utero by intramuscular injection of an adenoviral vector carrying hfIX cDNA exhibited high-level gene expression at birth and therapeutic , albeit continuously decreasing , plasma concentrations of hfIX over the entire 6 months of the study. Adenoviral vector spread to multiple organs was detected by polymerase chain reaction (PCR). Intramuscular, intraperitoneal or intravascular application of AAV vectors carrying hfIX cDNA led to much lower plasma concentrations of hfIX shortly after birth, which appeared to decline during the first month of life but stabilized in some of the mice at detectable levels. No signs of immune responses were found, either against the different viral vectors or against hfIX. Conclusion This study demonstrates for the first time that sustained systemic delivery of a therapeutic protein can be achieved by prenatal gene transfer. It thus shows the feasibility of gene therapy in utero and provides a basis for considering this concept as a preventive therapeutic strategy for haemophilia and perhaps also for other plasma protein deficiencies. Copyright © 2002 John Wiley & Sons, Ltd. [source] McLeod neuroacanthocytosis: Genotype and phenotype,ANNALS OF NEUROLOGY, Issue 6 2001Adrian Danek MD McLeod syndrome is caused by mutations of XK, an X-chromosomal gene of unknown function. Originally defined as a peculiar Kell blood group variant, the disease affects multiple organs, including the nervous system, but is certainly underdiagnosed. We analyzed the mutations and clinical findings of 22 affected men, aged 27 to 72 years. Fifteen different XK mutations were found, nine of which were novel, including the one of the eponymous case McLeod. Their common result is predicted absence or truncation of the XK protein. All patients showed elevated levels of muscle creatine phosphokinase, but clinical myopathy was less common. A peripheral neuropathy with areflexia was found in all but 2 patients. The central nervous system was affected in 15 patients, as obvious from the occurrence of seizures, cognitive impairment, psychopathology, and choreatic movements. Neuroimaging emphasized the particular involvement of the basal ganglia, which was also detected in 1 asymptomatic young patient. Most features develop with age, mainly after the fourth decade. The resemblance of McLeod syndrome with Huntington's disease and with autosomal recessive chorea-acanthocytosis suggests that the corresponding proteins,XK, huntingtin, and chorein,might belong to a common pathway, the dysfunction of which causes degeneration of the basal ganglia. [source] Cryptococcosis,a review of 13 autopsy cases from a 54-year period in a large hospital,APMIS, Issue 3 2007P. BENE From 1952 to 2005, 13 cases of cryptococcosis confirmed by postmortem examination were diagnosed in autopsy material from the University Hospital in Hradec Králové, the Czech Republic. Histologically, Cryptococcus was found in multiple organs (brain and spinal cord, lungs, lymph nodes, spleen, bone marrow, liver, kidneys and adrenal glands). The lungs and CNS were the organs most often involved. Only in two cases was the diagnosis of cryptococcal infection established during the patient's lifetime, in both presenting clinically as meningitis, with positive result of CSF cultivation. Data and issues of diagnostics and treatment of cryptococcosis are discussed. [source] Neurofibromatosis type 1 is a disorder of dysplasia: The importance of distinguishing features, consequences, and complications,BIRTH DEFECTS RESEARCH, Issue 1 2010Vincent Michael Riccardi BACKGROUND: The disorder neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene, which influences the availability of activated Ras and the latter's control of cellular proliferation. Emphasis on this aspect of NF1 has focused attention on the tumor suppression function of NF1 and thereby displaced attention from the gene's role in initial normal tissue formation, maintenance, and repair. METHODS: Clinical and neuroimaging data systematically compiled over more than 30 years are analyzed to document the involvement of multiple organs and tissues, often with an embryonic origin. In addition, recent literature based on selective knockout mouse experiments is cited to corroborate embryonic dysplasia as an element of NF1 pathogenesis. RESULTS: Tissue dysplasia, both ab initio and as part of tissue maintenance and wound healing, is a key clinical and pathogenetic aspect of NF1 and thereby provides a rationale for differentiating the elements of NF1 into features, consequences, and complications. CONCLUSIONS: NF1 is a histogenesis control gene that also has properties that overlap with those of a tumor suppressor gene. Both its neoplastic and dysplastic manifestations become more amenable to understanding and treatment if they are differentiated at three levels,specifically, features, consequences and complications. Birth Defects Research (Part A), 2010. © 2009 Wiley-Liss, Inc. [source] A New Quinoline Derivative MS-209 Reverses Multidrug Resistance and Inhibits Multiorgan Metastases by P-glycoprotein-expressing Human Small Cell Lung Cancer CellsCANCER SCIENCE, Issue 7 2001Hiroshi Nokihara Development of distant metastases and acquired multidrug resistance (MDR) are major problems in therapy for human small cell lung cancer (SCLC). MS-209 is a novel quinoline compound, which reverses P-glycoprotein (P-gp)-mediated MDR. We previously reported that MS-209 reversed in vitro MDR of human SCLC (SBC-3/ADM and H69/VP) cells expressing P-gp. In the present study, we determined the therapeutic effect of MS-209 in combination with chemotherapy against multiorgan metastases of MDR SCLC cells. SBC-3/ADM cells expressing P-gp were highly resistant to etoposide (VP-16), adriamycin (ADM), and vincristine (VCR) in vitro, compared with parental SBC-3 cells lacking P-gp expression. MS-209 restored chemosensitivity of SBC-3/ADM cells to VP-16, ADM, and VCR in a dose-dependent manner in vitro. Intravenous injection with SBC-3 or SBC-3/ADM cells produced metastatic colonies in the liver, kidneys and lymph nodes in natural killer (NK) cell-depleted severe combined immunodeficiency (SCID) mice, though SBC-3/ ADM cells more rapidly produced metastases than did SBC-3 cells. Treatment with VP-16 and ADM reduced metastasis formation by SBC-3 cells, whereas the same treatment did not affect metastasis by SBC-3/ADM cells. Although MS-209 alone had no effect on metastasis by SBC-3 or SBC-3/ADM cells, combined use of MS-209 with VP-16 or ADM resulted in marked inhibition of metastasis formation by SBC-3/ADM cells to multiple organs. These findings suggest that MS-209 reversed the MDR of SBC-3/ADM cells, but not SBC-3 cells, growing in the various organs, and inhibited metastasis formation in vivo. Therefore, this chemosensitizing agent, MS-209, may be useful for treatment of refractory SCLC patients with multiorgan metastases. [source] Dose- and Sex-related Carcinogenesis by N-Bis(2-hydroxypropyl)nitrosamine in Wistar RatsCANCER SCIENCE, Issue 4 2000Eduardo L. T. Moreira An initiation-promotion medium-term bioassay for detection of chemical carcinogens, developed in the male F344 rat, uses 0.1% N-bis(2-hydroxypropyl)nitrosamine (DHPN) among five genotoxic chemicals for the initiation of carcinogenesis in multiple organs. To establish this bioassay in the Wistar strain, the effects of two dose levels of DHPN were evaluated on the main DHPN rat target organs: lung, thyroid gland, kidneys and liver. Four groups of male and female animals were studied: Control,untreated group; Multi-organ initiated group (also referred to as DMBDD, based on the initials of the five initiators),treated sequentially with N-diethylnitrosamine (DEN, i.p.), N-methyl-N-nitrosourea (MNU, i.p.), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN, drinking water), N, ,N,-dimethylhydrazine (DMH, s.c.) and DHPN (drinking water) for 4 weeks; a third group treated with 0.1% DHPN in drinking water for 2 weeks and the last group treated with 0.2% DHPN in drinking water for 4 weeks. The animals were sacrificed after 30 weeks. DHPN at 0.2% induced preneoplasia in the liver and kidneys of rats of both sexes, the number and area of the putative preneoplastic liver glutathione S-transferase-positive hepatocyte foci being significantly increased in these animals. It also induced benign and malignant tumors in female and in male rats. However, there was no relationship between the increased incidence of preneoplastic lesions and tumor development in the 0.2% DHPN-exposed groups of both sexes. DHPN at 0.1% induced only a few preneoplastic lesions in the liver and kidney and no tumors in both male and female rats. A clear dose and sex-related carcinogenic activity of DHPN was registered, although Wistar rats of both sexes showed a relative resistance to the carcinogenic activity of this compound. [source] | |||||||||||||||||||||||||||||||