Metanephric adenoma of the kidney: a clinicopathological and molecular study of two cases.
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Adenoma↗
Biomedical subjects
Thomas Schubert
Publications and source records attributed to Thomas Schubert.
Collagen IX is indispensable for timely maturation of cartilage during fracture repair in mice.
Fracture repair recapitulates in adult organisms the sequence of cell biological events of endochondral ossification during skeletal development and growth. After initial inflammation and deposition of granulation tissue, a cartilaginous callus is formed which, subsequently, is remodeled into bone. In part, bone formation is influenced also by the properties of the extracellular matrix of the cartilaginous callus. Deletion of individual macromolecular components can alter extracellular matrix suprastructures, and hence stability and organization of mesenchymal tissues. Here, we took advantage of the collagen IX knockout mouse model to better understand the role of this collagen for organization, differentiation and maturation of a cartilaginous template during formation of new bone. Although a seemingly crucial component of cartilage fibrils is missing, collagen IX-deficient mice develop normally, but are predisposed to premature joint cartilage degeneration. However, we show here that lack of collagen IX alters the time course of callus differentiation during bone fracture healing. The maturation of cartilage matrix was delayed in collagen IX-deficient mice calli as judged by collagen X expression during the repair phase and the total amount of cartilage matrix was reduced. Entering the remodeling phase of fracture healing, Col9a1(-/-) calli retained a larger percentage of cartilage matrix than in wild type indicating also a delayed formation of new bone. We concluded that endochondral bone formation can occur in collagen IX knockout mice but is impaired under conditions of stress, such as the repair of an unfixed fractured long bone.
Animals↗
MR imaging of the intraarticular disk of the acromioclavicular joint: a comparison with anatomical, histological and in-vivo findings.
OBJECTIVE: To characterize MRI features of the intraarticular disk of the acromioclavicular joint. DESIGN: We studied the appearance of 11 acromioclavicular joints of six cadavers (subjects aged 57-89 years at the time of death) and six healthy shoulders on T1-weighted, T2 (TSE)-weighted, STIR and PD (fat saturated) magnetic resonance imaging (MRI) and compared the findings with observations during dissection and histological examination. RESULTS: Macroscopic examinations showed two wedge-shaped disks underneath the superior and above the inferior joint capsule in nine specimens. In two specimens the acromioclavicular joints were degenerated. Histologically, the disk tissue consisted of fibrocartilage whereas the joint cartilage was partly degenerated, containing zones of fibrocartilage amidst degenerated hyaline cartilage, which may explain the similar signal intensity of both structures in all sequences used. MR appearance of the intraarticular structures of the acromioclavicular joint was similar in cadaveric and healthy shoulders. CONCLUSIONS: The difficulties related to imaging the acromioclavicular joint may be explained by the anatomy. Similar signal intensity of cartilage and disk may be explained by their similar histological structure (fibrocartilage). MRI findings should be interpreted with respect to the variable anatomy. These results may serve as a basis for further radiological studies of the acromioclavicular joint.
Acromioclavicular Joint↗
Identification of keratins and analysis of their expression in carp and goldfish: comparison with the zebrafish and trout keratin catalog.
With more than 50 genes in human, keratins make up a large gene family, but the evolutionary pressure leading to their diversity remains largely unclear. Nevertheless, this diversity offers a means to examine the evolutionary relationships among organisms that express keratins. Here, we report the analysis of keratins expressed in two cyprinid fishes, goldfish and carp, by two-dimensional polyacrylamide gel electrophoresis, complementary keratin blot binding assay, and immunoblotting. We further explore the expression of keratins by immunofluorescence microscopy. Comparison is made with the keratin expression and catalogs of zebrafish and rainbow trout. The keratins among these fishes exhibit a similar range of molecular weights and isoelectric points, with a similar overall pattern on two-dimensional gels. In addition, immunofluorescence microscopy studies of goldfish and carp tissues have revealed the expression of keratins in both epithelial and mesenchymally derived tissues, as reported previously for zebrafish and trout. We conclude that keratin expression is qualitatively similar among these fishes, with goldfish and carp patterns being more similar to each other than to zebrafish, and the cyprinid fishes being more similar to each other than to the salmonid trout. Because of the detected similarity of keratin expression among the cyprinid fishes, we propose that, for certain experiments, they are interchangeable. Although the zebrafish distinguishes itself as being a developmental and genetic/genomic model organism, we have found that the goldfish, in particular, is a more suitable model for both biochemical and histological studies of the cytoskeleton, especially since goldfish cytoskeletal preparations seem to be more resistant to degradation than those from carp or zebrafish.
Amino Acid Sequence↗
High re-bleeding rate in young adults after subarachnoid haemorrhage from giant aneurysms.
Low re-bleeding rates within the first 14 days of aneurysmal subarachnoid haemorrhage are reported in young patients. Furthermore, re-bleeding rate for giant aneurysms does not exceed 20% according to the literature. Our own clinical impression is that the re-bleeding rate seems to be much higher in giant aneurysms than reported, particularly in young patients. The aim of this study was to evaluate re-bleeding rate after subarachnoid haemorrhage following rupture of giant aneurysms in a younger population. We reviewed records of 23 patients who were treated in our institution for subarachnoid haemorrhage from giant aneurysms between 1994 and 2003. By definition, the aneurysms were larger than 25 mm in diameter. Five patients were younger than 40 years of age at the time of the aneurysmal subarachnoid haemorrhage. All younger patients (<40 years of age) showed re-bleeding after the first subarachnoid haemorrhage within the first 14 days of the initial event. In four patients (20%) older than 40 years at the time of the haemorrhage re-bleeding could be observed within the first 14 days of subarachnoid haemorrhage. We can confirm the re-bleeding rate of approximately 20% in patients suffering from subarachnoid haemorrhage (SAH) in the group of patients older than 40 years of age. However, younger patients seem to be at much higher risk of re-bleeding from giant aneurysms.
Adult↗
Insulin prevents liver damage and preserves liver function in lipopolysaccharide-induced endotoxemic rats.
BACKGROUND/AIMS: Liver integrity and function are crucial for survival of patients suffering from trauma, operations or infections. Insulin decreased mortality and prevented the incidence of multi organ failure and infection in critically ill patients. The aim of the present study was to determine whether insulin exerts positive effects on hepatic homeostasis and function during endotoxemia. METHODS: Endotoxemic rats received either saline or insulin. Hepatic morphology and function was determined by measuring the effect of insulin on liver proteins, enzymes, hepatocyte apoptosis and proliferation including caspases-3 and -9 and Bcl-2. Intrahepatic ATP, glucose and lactate concentration were determined by bioluminescence. To determine possible molecular changes the effect of insulin on hepatic cytokine mRNA and gene profile analysis were assessed. RESULTS: Insulin significantly improved hepatic protein synthesis by increasing albumin and decreasing c-reactive protein, P<0.05. Insulin attenuated hepatic damage by decreasing AST and ALT, P<0.05. Improved liver morphology was due to decreased hepatocyte apoptosis along with decreased caspase-3 concentration and increased hepatocyte proliferation along with Bcl-2 concentration, P<0.05. Insulin decreased hepatic IL-1beta, IL-6 and MIF mRNA and improved hepatic glucose metabolism and glycolysis, P<0.05. GeneChip analysis revealed an anti-inflammatory effect of insulin. CONCLUSIONS: Insulin improves hepatic integrity, hepatic glucose metabolism and hepatic function by increasing cell survival and attenuating the hepatic inflammatory response in endotoxemic rats.
Acute-Phase Proteins↗
Enzyme-catalyzed regio- and enantioselective ketone reductions.
In this chapter, examples are given of the application of highly reactive prochiral ketones as substrates for enzymatic reductions. 3,5-Dioxocarboxylates are polyketide-like compounds that can be used to synthesize all of the possible stereoisomers of the corresponding 1,3-diols by means of regio- and enantioselective enzymatic reduction. The results obtained from an investigation into the usefulness of the resulting hydroxyl ketones and 1,3-diols in organic synthesis led to the development of non-natural functionalized ynones as a starting material for the enzymatic route to enantiopure propargylic alcohols. A broad variety of substituted acetylenic ketones can be reduced enantioselectively by the oxidoreductases Lactobacillus brevis ADH (LBADH), Candida parapsilosis carbonyl reductase (CPCR), horse liver ADH (HLADH) and Thermoanaerobium brockii ADH (TBADH). The resulting propargylic alcohols can be obtained in either enantiomeric form, since (R)- and (S)-specific oxidoreductases can be applied. By varying the size of the substituents, the enantiomeric excess can be tuned, or the enantioselectivity can even be reversed. The obtained highly functionalized enantiopure alcohols are synthetically flexible chiral building blocks that offer new synthetic strategies for target- and diversity-oriented synthesis.
Catalysis↗
Arthroscopic and histologic findings in Morquio's syndrome.
Mucopolysaccharidosis type IV A/B (Morquio's syndrome) is one of a heterogeneous group of lysosomal storage diseases characterized by accumulation of keratan sulfate in cells of connective tissue. From early childhood, the major orthopaedic manifestations are shortening of the trunk, spondylepiphyseal dysplasia, odontoid hypoplasia, upper cervical instability, lower-limb alignment problems, and degenerative joint disease. Most of the rare published case reports describe those characteristic clinical deformities of the skeleton. Our literature search showed that these striking arthroscopic findings have not been made public to date. We report a typical case of mucopolysaccharidosis type IV. We show and, in particular, correlate the arthroscopic with the histologic findings. In particular, the comparison between arthroscopy and light microscopy showed a remarkable extensive delamination of the chondral layer from subchondral bone of both knee joints. These findings should encourage further research, especially of the osteochondral borderline.
Adult↗
Cloning and functional characterization of a new Ski homolog, Fussel-18, specifically expressed in neuronal tissues.
The Sloan Kettering Virus (Ski) family of nuclear oncoproteins represses transforming growth factor-beta (TGF-beta) signaling through inhibition of transcriptional activity of Smad proteins. Here, we report the discovery of a new functional Smad suppressing element on chromosome 18 (Fussel-18). Fussel-18 encodes for a protein of 297 amino acids sharing characteristic structural features, significant homology and similar genomic organization with the homolog Ski family members, Ski and Ski-related novel sequence (Sno). In contrast to Ski and Sno, which are ubiquitously expressed in human tissues, in situ hybridization, RT-PCR, Western blot and immunohistochemistry revealed a highly specific expression pattern for Fussel-18 in neuronal tissues, especially in the cerebellum, the spinal cord and dorsal root ganglia, during both embryogenesis and adult stage. Functionally, we determined interaction of Fussel-18 with Smad 2 and Smad 3 together with an inhibitory activity on TGF-beta signaling. Fussel-18 is the first example of a Smad-binding protein with a highly restricted expression pattern within the nervous system.
Amino Acid Motifs↗
Contaminant seeding in bone by different irrigation methods: an experimental study.
OBJECTIVE: This study was designed to investigate the effectiveness of using various devices and manual procedures for cleansing bacterially contaminated bone tissue and to assess the risk of iatrogenic bacterial seeding in deep bone layers. METHODS: In an in vitro model, human femoral heads were contaminated with Escherichia coli and then cleansed with pulsatile high-pressure lavage, pulsatile low-pressure lavage, manual rinsing with bulb syringe lavage, or manual rinsing with combined brush cleaning. The numbers of bacteria that remained or those that were introduced by the rinsing procedures were quantitatively determined at depths of 0 to 1 cm, 1 to 2 cm, and 2 to 3 cm. RESULTS: Both pulsatile high-pressure lavage and brush cleaning were more effective than pulsatile low-pressure lavage and bulb syringe lavage for the purpose of surface cleansing. The differences were highly significant (P < 0.001). There was no significant difference in the decontaminating effect between pulsatile high-pressure lavage and brush cleaning (P = 0.24). The bacterial contamination attributable to the cleansing procedure, as measured at tissue depths of 1 to 2 cm and 2 to 3 cm, was significantly higher after pulsatile high-pressure lavage and after pulsatile low-pressure lavage than it was after bulb syringe lavage or brush cleaning (P < 0.001). CONCLUSION: In this in vitro investigation of cancellous bone, the brush cleansing was just as effective for getting rid of bacterial contamination as pulsatile high-pressure lavage, and carries a significantly lesser risk of iatrogenic bacterial seeding into deeper tissue layers. In the light of these promising results obtained by the cleansing of cancellous bone contaminated with bacteria, it would be desirable to perform supplementary in vitro and in vivo investigations into brush cleansing.
Aged↗
Expression of hypoxia-inducible carbonic anhydrases in brain tumors.
Malignant brain tumors exhibit distinct metabolic characteristics. Despite high levels of lactate, the intracellular pH of brain tumors is more alkaline than normal brain. Additionally, with increasing malignancy, brain tumors display intratumoral hypoxia. Carbonic anhydrase (CA) IX and XII are transmembrane isoenzymes that are induced by tissue hypoxia. They participate in regulation of pH homeostasis by catalyzing the reversible hydration of carbon dioxide. The aim of our study was to investigate whether brain tumors of different histology and grade of malignancy express elevated levels of CA IX and XII as compared to normal brain. We analyzed 120 tissue specimens from brain tumors (primary and metastatic) and normal brain for CA IX and XII expression by immunohistochemistry, Western blot, and in situ hybridization. Whereas normal brain tissue showed minimal levels of CA IX and XII expression, expression in tumors was found to be upregulated with increased level of malignancy. Hemangioblastomas, from patients with von Hippel-Lindau disease, also displayed high levels of CA IX and XII expression. Comparison of CA IX and XII staining with HIF-1alpha staining revealed a similar microanatomical distribution, indicating hypoxia as a major, but not the only, induction factor. The extent of CA IX and XII staining correlated with cell proliferation, as indicated by Ki67 labeling. The results demonstrate that CA IX and XII are upregulated in intrinsic and metastatic brain tumors as compared to normal brain tissue. This may contribute to the management of tumor-specific acid load and provide a therapeutic target.
Blotting, Western↗
Induction of heme oxygenase-1 before conditioning results in improved survival and reduced graft-versus-host disease after experimental allogeneic bone marrow transplantation.
Acute graft-versus-host disease (aGVHD) remains one of the main obstacles after allogeneic bone marrow transplantation (BMT). Using a well-established mouse BMT model in which aGVHD is induced across a haploidentical mismatch, we show that the expression of heme oxygenase-1 (HO-1) can be induced by cobalt-protoporphyrin IX (CoPP) in aGVHD target organs such as liver and bowel and that the induction of HO-1 before BMT results in improved overall survival and reduced aGVHD. Serum levels of proinflammatory cytokines were markedly reduced in CoPP-treated animals. Recipients displayed less damage to the intestinal mucosa, and this resulted in reduced serum lipopolysaccharide levels at day 6 after transplantation. Peritoneal cells and CD45(+) liver cells isolated from mice that received transplants strongly expressed HO-1 and displayed a reduction in the expression of activation markers such as CD11b, CD80, and major histocompatibility complex class I. This resulted in reduced T-cell activation ex vivo. These results demonstrate that the induction of HO-1 before high-dose conditioning protects the host in multiple ways and effectively ameliorates aGVHD.
Animals↗
Cytological evaluation of the tissue-implant reaction associated with subcutaneous implantation of polymers coated with titaniumcarboxonitride in vivo.
The aim of the present study was to evaluate the influence of titanium-coated polymers on the inflammatory response and remodeling of connective tissue during wound-healing processes. Discs of polyethyleneterephthalate (PET) and silicone as well as high-weight meshes of polypropylene (PP) were coated with a titaniumcarboxonitride (Ti(C,N,O)) layer by a plasma-assisted chemical vapor deposition process (PACVD) and implanted subcutaneously in the dorsal lumbar region of Wistar rats. Light microscopic and histological evaluation of capsule thickness, capsule quality, implant-tissue interface and collagen composition was performed 7, 14, 21 and 28 days post-operatively. All implants were surrounded by a fibrous capsule with decreasing thickness after 2-4 weeks post-implantation. Titaniumcarboxonitride-coated polymers showed no significant differences in capsule thickness and inflammatory cellular response. An increased collagen type III/I ratio, especially for titaniumcarboxonitride-coated materials, was found in week one after implantation remaining elevated up to week 4. This might be associated with disordered collagen metabolism and immature scar reaction. In contrast to previous in vitro experiments, Ti-coating of polymers did not improve biocompatibility after subcutaneous implantation in rats. Material reduction to low-weight meshes and enlargement of pore size may demonstrate a benefit of Ti-coated meshes with an increased biocompatibility.
Animals↗
Insulin treatment improves hepatic morphology and function through modulation of hepatic signals after severe trauma.
OBJECTIVE: The purpose of the present study was to determine the effect of insulin therapy on hepatic function, structure, and hepatic mRNA and protein cytokine expression during the hypermetabolic cascade post burn. SUMMARY BACKGROUND DATA: Liver function and morphology are crucial for survival of patients suffering from trauma, operations, or infections. Insulin decreased mortality and prevented the incidence of multiorgan failure in critically ill patients. METHODS: Rats received a thermal injury and were randomly divided into the insulin or control group. Our outcome measures encompassed the effect of insulin on hepatic proteins, hepatic pro- and anti-inflammatory cytokines mRNA and proteins, hepatocyte proliferation, including Bcl-2 and hepatocyte apoptosis, with caspases-3 and caspases-9. RESULTS: Insulin significantly improved hepatic protein synthesis by increasing albumin and decreasing c-reactive protein and fat (P < 0.05). Insulin decreased the hepatic inflammatory response signal cascade by decreasing hepatic pro-inflammatory cytokines mRNA and proteins IL-1beta and tumor necrosis factor at pretranslational levels. Insulin increased hepatic cytokine mRNA and protein expression of IL-2 and IL-10 at a pretranslational level when compared with controls (P < 0.05). Insulin increased hepatocyte proliferation along with Bcl-2 concentration, while decreasing hepatocyte apoptosis along with decreased caspases-3 and -9 concentration, thus improving liver morphology (P < 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro-inflammatory and increasing the anti-inflammatory cascade, thus restoring hepatic homeostasis, which has been shown to be critical for organ function and survival of critically ill patients.
Animals↗
Exogenous liposomal IGF-I cDNA gene transfer leads to endogenous cellular and physiological responses in an acute wound.
The purpose of the present study was to examine whether exogenous liposomal cDNA gene transfer is recognized by the cell and causes endogenous cellular and physiological responses. When administered as a protein, IGF-I is known to cause adverse side effects due to lack of cellular responses. Therefore, we used IGF-I cDNA as a vector to study cellular and physiological effects after liposomal administration to wounded skin. Sprague-Dawley rats were given a scald burn to inflict an acute wound and were divided into two groups to receive weekly subcutaneous injections of liposomes plus the Lac-Z gene (0.2 microg vehicle) or liposomes plus the IGF-I cDNA (2.2 microg) and Lac Z gene (0.22 microg). Transfection was confirmed by histochemical assays for beta-galactosidase. Planimetry, immunological assays, and histological and immunohistochemical techniques were used to determine molecular mechanisms after gene transfer, protein expression, and dermal and epidermal regeneration. IGF-I cDNA transfer increased IGF-I protein expression and caused concomitant cellular responses by increasing IGF binding protein (IGFBP)-3 and decreasing IGFBP-1. IGF-I cDNA gene transfer increased keratinocyte growth factor expression and exerted promitogenic antiapoptotic effects on basal keratinocytes, thus improving epidermal regeneration. IGF-I cDNA improved dermal regeneration by an increased collagen deposition and morphology. IGF-I cDNA increased VEGF concentrations and thus neovascularization. Exogenous-administered IGF-I cDNA is recognized by the cell and leads to similar intracellular responses as the endogenous gene. Liposomal IGF-I gene transfer further leads to improved dermal and epidermal regeneration by interacting with other growth factors.
Animals↗
Maxillary actinomycosis in an immunocompromised patient with longstanding vasculitis treated with mycophenolate mofetil.
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Actinomycosis↗
TNF-independent development of transient anemia of chronic disease in a mouse model of protracted septic peritonitis.
TNF is considered one of the inflammatory cytokines and contributes mainly to the generation of anemia of chronic disease (ACD). In nude mice TNF has been reported to impair iron metabolism and erythropoiesis, leading to anemia with a low serum iron and preserved iron stores. In this work, we established a murine model for ACD based on sublethal cecal ligation and puncture (CLP) with ensuing protracted peritonitis. Starting on Day 3 after CLP, a severe protracted depression of erythropoiesis in the bone marrow was noted. Two weeks after CLP, we observed a moderate normochromic anemia, low serum iron concentration, and preserved iron stores consistent with transient ACD. To determine whether TNF contributes to the development of ACD in vivo, we neutralized TNF after CLP shortly before and during the phase of most severe bone marrow depression to prevent anemia. Additionally, we studied TNF-deficient mice undergoing CLP. Two weeks after CLP, we determined red blood count, hemoglobin concentration, hematocrit, serum iron concentration, and iron stores in spleens of wild-type mice, TNF-deficient mice, and mice after neutralization of TNF. Neutralization of TNF after CLP could not prevent mice from contracting anemia. Accordingly, TNF-deficient mice developed anemia to the same extent as wild-type mice. Serum iron concentration was lowered and iron stores were overloaded in both TNF-deficient and wild-type mice after CLP. Our results clearly demonstrate that TNF is not a mediator of ACD in our model with transient anemia induced by protracted septic peritonitis.
Anemia↗
Interaction of exogenous liposomal insulin-like growth factor-I cDNA gene transfer with growth factors on collagen expression in acute wounds.
Growth factors have been shown to modulate the complex cascade of wound healing, however, interaction between different growth factors during dermal and epidermal regeneration is still not entirely defined. We have recently shown that exogenous liposomal gene transfer of cDNA results in physiologic expression and response in an acute wound. In the present study we determined the interaction between insulin-like growth factor-I (IGF-I), a mesenchymal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors on collagen synthesis in an acute wound. Sprague-Dawley rats were given a scald burn to inflict an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus a beta-galactosidase containing plasmid (Lac Z [0.2 microg, vehicle]), or liposomes plus the IGF-I cDNA containing plasmid (2.2 microg) and Lac Z (0.2 microg). Immunological assays, histological and immunohistochemical techniques were used to determine growth factor concentration and different types of collagen (I, III, and IV) after IGF-I cDNA gene transfer. IGF-I cDNA transfer accelerated reepithelization and was associated with increased levels of IGF-I, fibroblast growth factor, keratinocyte growth factor, vascular endothelial cell growth factor, and platelet-derived growth factor protein expression. IGF-I cDNA had no effect on transforming growth factor-beta. IGF-I cDNA significantly increased type IV collagen while it had no effect on types I and III collagen. Exogenously administered IGF-I cDNA increased protein concentrations of keratinocyte growth factor, fibroblast growth factor, platelet-derived growth factor, and type IV collagen. We conclude that liposomal IGF-I gene transfer can accelerate wound healing without causing an increase in types I and III collagen expression.
Animals↗