Cardiovascular surgery in renal failure patients with or without subsequent renal transplantation.
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Aged↗
Biomedical subjects
A Hartmann
Publications and source records attributed to A Hartmann.
Inoculation of an atrazine-degrading strain, Chelatobacter heintzii Cit1, in four different soils: effects of different inoculum densities.
The possibility to improve atrazine degradation in soils by bioaugmentation was studied. The atrazine-mineralizing strain, Chelatobacter heintzii Cit1, was inoculated in four sterile and four non-sterile soils, at varying inoculum densities. Two soils, which had shown enhanced atrazine mineralization, were used to determine which inoculum density was capable of restoring their original mineralizing capacity after sterilization. The two other soils, with intermediate and low capacity to mineralize atrazine, were used in order to demonstrate that atrazine mineralization in such soils could be improved by inoculation. Mineralization kinetics were fitted using the Gompertz model. In the case of soils adapted to atrazine mineralization, inoculation of C. heintzii did not accelerate the rate of atrazine mineralization, which was essentially performed by the indigenous microflora. However, with soils that did not mineralize atrazine, the introduction of 10(4) cfug(-1) resulted in a 3-fold increase of atrazine mineralization capacity.
Atrazine↗
Changes in GAD67 mRNA expression evidenced by in situ hybridization in the brain of R6/2 transgenic mice.
Huntington's disease is an autosomal dominant disorder with degeneration of medium size striatal neurones. As the disease evolves, other neuronal populations are also progressively affected. A transgenic mouse model of the disease (R6/2) that expresses exon 1 of the human Huntington gene with approximately 150 CAG repeats has been developed, but GABA concentrations are reported to be normal in the striatum of these animals. In the present study, we analysed the status of GABAergic systems by means of glutamic acid decarboxylase (GAD)67 mRNA in situ hybridization in the brain of R6/2 transgenic mice and wild-type littermates. We show that GAD67 expression is normal in the striatum, cerebellum and septum but decreased in the frontal cortex, parietal cortex, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata of R6/2 mice. These data, which may, in part, account for the behavioural changes seen in these animals, indicate that at 12.5 weeks of age the pathological features seen in the mice differ from those seen in humans with Huntington's disease.
Animals↗
Recommendations for conducting the in vivo alkaline Comet assay. 4th International Comet Assay Workshop.
The in vivo alkaline single cell gel electrophoresis assay, hereafter the Comet assay, can be used to investigate the genotoxicity of industrial chemicals, biocides, agrochemicals and pharmaceuticals. The major advantages of this assay include the relative ease of application to any tissue of interest, the detection of multiple classes of DNA damage and the generation of data at the level of the single cell. These features give the Comet assay potential advantages over other in vivo test methods, which are limited largely to proliferating cells and/or a single tissue. The Comet assay has demonstrated its reliability in many testing circumstances and is, in general, considered to be acceptable for regulatory purposes. However, despite the considerable data published on the in vivo Comet assay and the general agreement within the international scientific community over many protocol-related issues, it was felt that a document giving detailed practical guidance on the protocol required for regulatory acceptance of the assay was required. In a recent meeting held in conjunction with the 4th International Comet Assay Workshop (Ulm, Germany, 22-25 July 2001) an expert panel reviewed existing data and recent developments of the Comet assay with a view to developing such a document. This paper is intended to act as an update to the more general guidelines which were published as a result of the International Workshop on Genotoxicity Test Procedures. The recommendations are also seen as a major step towards gaining more formal regulatory acceptance of the Comet assay.
Animals↗
The role of glial reaction and inflammation in Parkinson's disease.
The glial reaction is generally considered to be a consequence of neuronal death in neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, and Parkinson's disease. In Parkinson's disease, postmortem examination reveals a loss of dopaminergic neurons in the substantia nigra associated with a massive astrogliosis and the presence of activated microglial cells. Recent evidence suggests that the disease may progress even when the initial cause of neuronal degeneration has disappeared, suggesting that toxic substances released by the glial cells may be involved in the propagation and perpetuation of neuronal degeneration. Glial cells can release deleterious compounds such as proinflammatory cytokines (TNF-alpha, Il-1beta, IFN-gamma), which may act by stimulating nitric oxide production in glial cells, or which may exert a more direct deleterious effect on dopaminergic neurons by activating receptors that contain intracytoplasmic death domains involved in apoptosis. In line with this possibility, an activation of proteases such as caspase-3 and caspase-8, which are known effectors of apoptosis, has been reported in Parkinson's disease. Yet, caspase inhibitors or invalidation of TNF-alpha receptors does not protect dopaminergic neurons against degeneration in experimental models of the disease, suggesting that manipulation of a single signaling pathway may not be sufficient to protect dopaminergic neurons. In contrast, the antiinflammatory drugs pioglitazone, a PPAR-gamma agonist, and the tetracycline derivative minocycline have been shown to reduce glial activation and protect the substantia nigra in an animal model of the disease. Inhibition of the glial reaction and the inflammatory processes may thus represent a therapeutic target to reduce neuronal degeneration in Parkinson's disease.
Animals↗
In situ identification of intracellular bacteria related to Paenibacillus spp. in the mycelium of the ectomycorrhizal fungus Laccaria bicolor S238N.
Bacterial proliferations have recurrently been observed for the past 15 years in fermentor cultures of the ectomycorrhizal fungus Laccaria bicolor S238N, suggesting the presence of cryptic bacteria in the collection culture of this fungus. In this study, intracellular bacteria were detected by fluorescence in situ hybridization in combination with confocal laser scanning microscopy in several collection subcultures of L. bicolor S238N. They were small (0.5 micro m in diameter), rare, and heterogeneously distributed in the mycelium and were identified as Paenibacillus spp. by using a 16S rRNA-directed oligonucleotide probe initially designed for bacteria isolated from a fermentor culture of L. bicolor S238N.
Agaricales↗
Alterations in p53 predict response to preoperative high dose chemotherapy in patients with gastric cancer.
AIMS: To evaluate the usefulness of molecular markers in predicting histopathological and clinical response to preoperative high dose chemotherapy (HDCT) and survival of patients with advanced gastric cancer. METHODS: In a phase II trial, 25 patients with metastatic gastric cancer received preoperative tandem HDCT consisting of etoposide, cisplatin, and mitomycin, followed by autologous bone marrow transplantation to achieve surgical resectability. Samples before and after treatment, from normal and tumour tissue, were characterised histopathologically, and both p53 and BAX expression was analysed by immunohistochemistry. Pretreatment formalin fixed, paraffin wax embedded samples from normal and tumour tissue were microdissected, and the extracted DNA was preamplified using improved primer extension preamplification polymerase chain reaction. Detection of microsatellite instability (MSI) or loss of heterozygosity (LOH) was performed using markers for p53, BAX, BAT25, BAT26, D2S123, D17S250, and APC. Exons 5-9 of the p53 gene were sequenced directly on ABI 373. RESULTS: Four parameters were significantly associated with response to chemotherapy and prolonged overall survival: positive p53 immunostaining, positive p53 mutation status before chemotherapy, strong histological regression induced by preoperative HDCT, and surgical treatment. Patients's sex or age, tumour location or stage, lymph node status, Lauren classification, MSI, or LOH did not influence duration of survival significantly in this high risk population. CONCLUSION: Positive p53 immunostaining and p53 mutation status in pretreatment tumour biopsies might be useful molecular predictors of response and prognosis in patients with advanced gastric cancer treated by preoperative HDCT.
Adult↗
Doppler examination of the allografted kidney.
A comprehensive ultrasound examination of the transplanted kidney includes a Doppler examination. Duplex Doppler, color Doppler and power Doppler can all reveal important information. In addition, calculation of the resistance and pulsatility indices to quantify changes in the spectral Doppler waveform can be of great help, particularly in the first weeks and months following a transplantation. The Doppler part of the examination should evaluate the vessels to and from the transplant, as well as the parenchyma with calculations of indices to detect the presence of increased vascular resistance. The conclusions drawn from the Doppler-derived information combined with the results from gray-scale scanning and clinical information will very often be of clinical significance for the handling of the patient.
Humans↗
[Molecular changes in development and progression of urothelial carcinoma].
The multistep development of malignant tumors with increasing accumulation of genetic alterations from preneoplastic lesions to invasive carcinoma is an accepted model of carcinogenesis. Urothelial carcinoma of the bladder and upper urinary tract is an interesting model system to study tumor development and progression. There is both clinical and molecular evidence that urothelial carcinoma can be divided in two groups with different characteristics: 1) well differentiated genetic stable and mostly superficial papillary tumors with frequent recurrence and low progression risk and 2) poorly differentiated mostly solid and invasive tumors with a high number of genetic alterations. The aim of the studies summarized in this manuscript were: 1) to identify genetic changes with importance for urothelial carcinogenesis by investigation of preneoplastic and early neoplastic urothelial lesions, 2) to define molecular markers for progression of papillary carcinoma, and 3) to investigate the importance of microsatellite instability and mismatch repair defects for development of tumors of the upper urinary tract which are frequently found within the HNPCC syndrome. The investigation of urothelial hyperplasias, dysplasias and carcinoma in situ by deletion mapping (LOH analysis), FISH, CGH and mutation detection revealed that urothelial hyperplasias are precursors of papillary bladder tumors and flat dysplasias can be regarded as precursors of solid bladder cancers. In bladder cancer patients, there are genetic alterations already detectable in histologically inconspicous urothelium. The investigation of papillary bladder cancers for progression-related genetic alterations showed that mutations in the wnt pathway genes APC and beta-Catenin do not play an important role in urothelial carcinogenesis. Instead, the expression of the antagonistic wnt-related genes WIF-1 and sFRPI is strongly reduced in bladder cancer and associated with poor prognosis in papillary tumors. Loss of sFRP1 expression is not due to gene mutation but to epigenetic inactivation by promoter hypermethylation and is related to deletions at chromosome 8p12. In contrast to bladder cancers, tumors of the ureter and renal pelvis develop through a different genetic pathway in 30% of cases. The loss of mismatch repair proteins (hMSH2, hMLH1 or hMSH6) leads to a mutator phenotype with accumulation of genetic alterations in multiple repetitive sequences (microsatellite instability, MSI). MSI-positive tumors were predominantly located in the ureter and showed a lower tumor stage and grade and papillary and frequently inverted growth pattern. They were more frequent in females and younger patients and had a higher incidence of colorectal carcinomas and other tumors in the family. Chromosome 9 deletions, a hallmark of urothelial carcinomas, and the number of chromosomal alterations as detected by CGH analysis were significantly less frequent in these tumors. These data strongly suggest a distinct molecular pathway in the development of upper urinary tract tumors with mutator phenotype.
Cell Transformation, Neoplastic↗
Long-term culture of islets abrogates cytokine-induced or lymphocyte-induced increase of antigen expression on beta cells.
BACKGROUND: Immunogenicity of a graft depends on its expression of major histocompatability complex (MHC) antigens and adhesion molecules and on the amount of intragraft leukocytes, the so-called passenger leukocytes. Although long-term culture reduces passenger leukocytes, permanent acceptance is not necessarily observed after allogeneic transplantation. Because little is known about antigen expression on the surface of islet cells after long-term culture of islets, we investigated whether antigen expression of pancreatic beta cells is influenced by long-term culture and whether long-term culture can counteract the increase of antigen expression induced by cytokines or by allogeneic lymphocytes. We also investigated whether long-term cultured islets were able to stimulate allogeneic lymphocytes to produce cytokines. METHODS: Isolated LEW.1A (RT1a) rat islets of Langerhans were cultured for 14 and 28 days. Precultured and freshly-isolated islets were then incubated for 2 days with rat recombinant interferon (rIFN)-gamma (1,000 IU/mL), or were co-cultured for 4 days with LEW.1W (RT1u) splenic lymphocytes. RESULTS: Long-term culture significantly reduced CD45 leukocytes within the islets and decreased the amount of beta cells expressing intercellular adhesion molecule (ICAM)-1, whereas MHC antigen expression remained unchanged. After incubation of freshly isolated islets with IFN-gamma induction of MHC class II antigens on beta cells, an increase of MHC class I antigen density and an enhancement of ICAM-1+ beta cells were observed. Similar results were found after co-culturing with allogeneic lymphocytes. Using precultured islets, the induction of MHC class II on beta cells by IFN-gamma was still present but significantly lower and was absent after co-culture with allogeneic lymphocytes. Enhancement of ICAM-1+ beta cells by IFN-gamma or by allogeneic lymphocytes was markedly lowered because of preculturing. The proportion of MHC class I beta cells remained unchanged; however, antigen density of long-term cultured islets (28 days) could not be enhanced by allogeneic lymphocytes. Precultured islets were not able to stimulate allogeneic lymphocytes to produce and release normal amounts of cytokines (IFN-gamma or interleukin [IL]-2). CONCLUSIONS: In conclusion, in addition to reduction-depletion of passenger leukocytes, long-term culturing of islets also is able to counteract the IFN-gamma-induced or allogeneic lymphocyte-induced increase of antigen expression. Therefore, initiation of rejection and generation of cytotoxic cells might be altered or timely delayed when long-term cultured islets are transplanted. The variable and conflicting in vivo results after transplantation of long-term cultured islets might be explained by the possible indirect antigen presentation, which is not influenced by islet preculture.
Animals↗
Local intra-arterial thrombolysis in the carotid territory: does recanalization depend on the thromboembolus type?
Little is known about whether recanalization of carotid territory occlusions by local intra-arterial thrombolysis (LIT) depends on the type of the occluding thromboembolus. We retrospectively analysed the records of 62 patients with thromboembolic occlusions of the intracranial internal carotid artery (ICA) bifurcation or the middle cerebral artery who were undergoing LIT with urokinase within 6 h of symptom onset. We determined the influence of thromboembolus type (according to the TOAST criteria), thromboembolus location, leptomeningeal collaterals, time interval from onset of symptoms to onset of thrombolysis, and patient's age on recanalization. The thromboembolus type was atherosclerotic in six patients, cardioembolic in 29, of other determined etiology in four, and of undetermined etiology in 23 patients. Thirty-three (53%) thromboembolic occlusions were recanalized. The thromboembolus location but not the TOAST stroke type nor other parameters affected recanalization. In the TOAST group of patients with cardioembolic occlusions recanalization occurred significantly less frequently when transoesophageal echocardiography showed cardiac thrombus. The present study underlines the thromboembolus location as being the most important parameter affecting recanalization. The fact that thromboembolic occlusions originating from cardiac thrombi had a lower likelihood of being resolved by thrombolysis indicates the thromboembolus type as another parameter affecting recanalization.
Carotid Artery Thrombosis↗
Influence of nonylphenol on the microbial community of lake sediments in microcosms.
In this study the impact of nonylphenol, an estrogenic degradation product of alkylphenol polyethoxylates, on the microbial community structure in contaminated sediments of aquatic microcosms using in situ hybridization with fluorescently labeled oligonucleotides probes was investigated. A positive correlation between nonylphenol concentration and cell numbers of bacteria and microfungi as well as an increase in the numbers of active bacteria was found. However, the ratio between total microorganisms and active bacteria remained unchanged. A large fraction of the cells could be identified using group specific oligonucleotide probes. A slight change in the composition of the microbial community structure was observed, with Gram-positive bacteria with high DNA G + C-content becoming more abundant at higher concentrations of nonylphenol.
Bacteria↗
FADD: A link between TNF family receptors and caspases in Parkinson's disease.
Fas-associating protein with a death domain (FADD) is a proximal adaptor protein of the tumor necrosis factor (TNF) receptor family death pathway. This human postmortem study showed a significant decrease in the percentage of FADD-immunoreactive dopaminergic (DA) neurons in the substantia nigra pars compacta of patients with PD compared with controls (-24.8%). This decrease correlated with the known selective vulnerability of nigral DA neurons in PD, suggesting that this pathway contributes to the susceptibility of DA neurons in PD to TNF-mediated apoptosis.
Adaptor Proteins, Signal Transducing↗
[Angiogenesis--anti-angiogenesis. Significance for tumor growth and metastasis].
Angiogenesis plays an important role in the local growth and metastasis of a variety of malignant tumors. During the past three decades so-called angiogenesis factors have been discovered and characterized in more detail. These are the major contributors to angiogenesis. The term angiogenesis factors includes other functionally heterogeneous molecules. The best characterized angiogenesis factors are endothelial growth factors, such as "vascular endothelial growth factor" (VEGF), "fibroblast growth factor" (FGF), "platelet-derived growth factor" (PDGF), Angiogenin and interleukin-8 (IL-8). However, members of the family of matrix metalloproteinases are also included. The list of factors involved in angiogenessis and their receptors are increasing steadily as does the list of molecules with antiangiogenic capacity. The latter comprises the endogenous factors, Angiostatin, Endostatin, Thrombospondin-1 and 2, and chemical compounds, such as the Fumagillin derivative, AGM-1470, or inhibitors of matrix metalloproteinases. These have attracted more interest during the past years, since investigations on these molecules foster hope for new therapeutic strategies. Some of these antiangiogenic factors have already been used in various therapeutic approaches to influence tumor growth. While impressive results have been obtained in well controlled experimental animal models, the results of clinical studies in humans fall short of these successes. This is at least in part due to the fact that angiogenesis of tumors is a complex process based on the interaction of a variety of factors. The present article summarizes the current knowledge about tumor angiogenesis with a particular emphasis on antiangiogenic molecules. The presented data open new interesting therapeutic perspectives for future dermatology.
Angiogenesis Inducing Agents↗
Kidney function and glomerulopathy over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria.
AIMS/HYPOTHESIS: We aimed to investigate prospectively the interrelation between kidney function and glomerular morphological changes over 8 years in young patients with Type I (insulin-dependent) diabetes mellitus and microalbuminuria. METHODS: Kidney biopsies were taken at baseline and after 8 years in 18 subjects who were 20 years of age (19-29 mean and range), had duration of diabetes for 11 years (7-18), and who had an albumin excretion rate of 45 microg/min (15-194). The glomerular ultrastructural parameters were analysed using stereological methods. RESULTS: At the end of the study three patients had an increased albumin excretion rate of more than 25 % a year, two of whom developed overt nephropathy. Glomerular filtration rate declined 2.3 ml/min x 1.73 m(-2) x yr(-1). Glomerular volume, volume fractions of matrix and mesangium, and basement membrane thickness showed an increase over the 8 years. Multiple regression analysis showed that mean 8-years HbA(1 c), matrix volume fraction(baseline) and basement membrane thickness BMT(baseline) accounted for 70 % of the variation in AER at the end of the study. Mesangial volume fraction(baseline,) glomerular filtration fraction(baseline,) and mean 8-year HbA(1 c) accounted for 73 % of the change in glomerular filtration rate from baseline. Smoking was strongly associated with the glomerular filtration rate at baseline ( r = 0.65). When glomerular filtration rate(baseline) was omitted from the equation, smoking was the only significant parameter linked to the change in glomerular filtration rate from the baseline. CONCLUSION/INTERPRETATION: In patients who had diabetes for 20 years, long-term hyperglycaemia and glomerulopathy found 8 years prior to the study, and possibly smoking, affected renal function (i. e. albumin excretion rate and glomerular filtration rate).
Adult↗
Structural changes in renal arterioles in Type I diabetic patients.
AIMS/HYPOTHESIS: We aimed to obtain data on arteriolar structure in a follow-up study of microalbuminuric diabetic patients. METHODS: Kidney biopsies were obtained at baseline and after 8 years in 18 Type I (insulin-dependent) diabetic patients. Albumin excretion rate, blood pressure and HbA(1C) were measured regularly, and the glomerular filtration rate (GFR) was measured at the time of the kidney biopsy. The biopsy was embedded into plastic blocks and serially sectioned with 1 microm sections. In levels 25 microm apart, afferent and efferent arteriolar profiles were identified and digitised in the electron microscope. The extra-cellular matrix as volume fraction of the media was measured, and estimates of thickness of matrix, media, endothelium and lumen were obtained. Baseline and follow-up biopsies were studied concomitantly. RESULTS: A large increase was seen in matrix volume fraction in afferent ( p = 0.0001) and in efferent arterioles ( p = 0.0004). Estimated thickness of media and matrix increased, whereas endothelial cell thickness decreased, over the 8 years. There was a correlation between the parameters of diabetic glomerulopathy and arteriolar parameters in the biopsies done at 8 years, basement membrane thickness compared with afferent matrix volume fraction: r = 0.74, p = 0.0005. Also aggravation of glomerulopathy and arteriolar structure over 8 years showed positive correlation. Arteriolar parameters correlated with the albumin excretion rate (AER) and inversely with GFR. CONCLUSION/INTERPRETATION: The arteriolar accumulation of matrix parallels that taking place in glomeruli and shows association with functional parameters over 8 years in Type I diabetic patients with microalbuminuria. These changes are considered an important part of the structural lesions in the diabetic kidney underlying the development of diabetic nephropathy.
Adult↗
Current state of stem cell research for the treatment of Parkinson's disease.
Current findings suggest that multipotent stem cells may be suitable for cell replacement therapies in the treatment of neurodegenerative disorders. Embryonic stem (ES) cells are pluripotent cells isolated from the inner cell mass of the preimplantation blastocyst, which give rise to all cells in the organism. Similarly, multipotent stem cells are also able to regenerate, but are believed to have a more restricted potential than ES cells, and are often defined by the organ from which they are derived. Neural stem cells have been categorized as multipotent stem cells derived from the nervous system with the capacity to regenerate and to give rise to cells belonging to all three cell lineages in the nervous system: neurons, oligodendrocytes, and astrocytes. It is hoped that research on stem cells may reveal methods for producing an infinite supply of dopamine neurons for transplant into Parkinson's disease (PD) patients. The problem is controlling cell growth and differentiation. We will briefly review the current state of stem cell research and will critically discuss the potential of stem cells for the treatment of PD.
Brain Tissue Transplantation↗
Perfusion and molecular diffusion-weighted MR imaging of the brain: in vivo assessment of tissue alteration in cerebral ischemia.
The combined use of perfusion imaging (PI) and diffusion-weighted imaging (DWI) is opening a new window into the processes that occur during the first hours of ischemia. DWI detects changes in molecular diffusion associated with cytotoxic edema. PI characterizes the degree of regional hypoperfusion. Regions showing mismatches between DWI and PI, i.e. hypoperfused areas with normal diffusion behavior are considered potentially salvageable. We present results of 11 patients with an occlusion of the middle cerebral artery stem and spontaneous stroke evolution. Whereas the infarct was clearly visible on initial DWI and PI, surrounding tissue at risk of infarction was marked in all patients by an increased blood volume and transit time, but only in a subgroup (n = 3) where alteration were more pronounced this tissue at risk was progressively infarcted. These human DWI and PI data show alterations in the area of tissue at risk which correlates with infarct progression.
Adolescent↗