[Molecular pathogenesis of thyroid tumors].
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Adenocarcinoma, Follicular↗
Biomedical subjects
K Krause
Publications and source records attributed to K Krause.
Lesions in the cerebellar fastigial nucleus have a small effect on the hyperpnea needed to meet the gas exchange requirements of submaximal exercise.
The purpose of this study was to test the hypothesis that an intact cerebellar fastigial nucleus (CFN) is necessary for the hyperpnea to meet the gas exchange needs of submaximal exercise. Bilateral stainless steel microtubules were implanted in the cerebellum inside (n = 12) or outside (n = 2) the CFN for injection (0.5 to 10 microl) of the neurotoxin ibotenic acid. All goats had difficulty maintaining normal posture and walking for up to 1 mo after the implantation of the microtubules and again for hours or days after the neurotoxin was injected. Postmortem histology indicated there were 55% fewer living neurons (P < 0.001, n = 9, 3,720 +/- 553 vs. 1,670 +/- 192) in the CFN of the experimental goats compared with a control group of goats. As is typical for goats before implantation of the microtubules, the decrease in arterial Pco(2) from rest during mild and moderate treadmill exercise was 2.0 +/- 0.39 and 3.5 +/- 0.45 Torr, respectively. Implantation of the microtubules did not significantly change this exercise hyperventilation. However, neurotoxic lesioning with 10 mul ibotenic acid significantly (P < 0.05) attenuated the decrease in arterial Pco(2) by 1.3 and 2.8 Torr at the first and second workload, respectively. The modest attenuation of the exercise hypocapnia at both workloads in CFN-lesioned goats suggests that the CFN is part of the control system that enables the ventilatory response to meet the gas exchange requirements of submaximal exercise.
Animals↗
CO2/H+ chemoreceptors in the cerebellar fastigial nucleus do not uniformly affect breathing of awake goats.
Our objective in this study was to test the hypothesis that focal acidosis (FA) in the cerebellar fastigial nucleus (CFN) of awake goats arising from global brain acidosis induced by increasing inspired CO2 will increase breathing. FA was created by reverse microdialysis of mock cerebral spinal fluid, equilibrated with 6.4, 25, 50, or 80% CO2 through chronically implanted microtubules (cannula). Dialysis with 6.4% CO2 had no significant effects on any physiological parameters. However, microdialysis at higher levels of CO2 increased pulmonary ventilation (V(I)) in one group of studies and decreased V(I) in a second group and the difference between the groups was significant (t = 9.16, P < 0.001). In one group of studies (n = 8), FA with 50 and 80% CO2 significantly increased (P < 0.05) Vi by 16 and 12%, respectively, and significantly increased (P < 0.05) heart rate by 13 and 9%, respectively. In contrast, in another group of studies (n = 6), FA with 25 and 50% CO2 significantly decreased (P < 0.05) Vi by 7 and 10%, respectively. In this group oxygen consumption was decreased during dialysis with 80% CO2. On the basis of histology, we estimate that the increased and decreased responses were associated with FA primarily in the rCFN and cCFN, respectively. We conclude that there are CO2/H+-sensitive neurons in the CFN that do not uniformly affect breathing. In addition, the significant changes in heart rate and oxygen consumption during FA indicate that the CFN can also influence non-respiratory-related control systems.
Acidosis, Respiratory↗
[High-dose rate brachytherapy for high-risk prostate cancer].
To estimate disease-free survival it is necessary to allocate patients into tumor risk groups: locally advanced prostate carcinoma with extracapsular spread or localized prostate carcinoma of tumor stage T2c or one of the risk factors PSA >20 or Gleason > or =8 apply for the high-risk group. Intermediate-risk carcinomas are those belonging to tumor stage T2b or with PSA >10-20 or Gleason 7. Particularly for patients with intermediate and high-risk disease early PSA relapse is of major interest. This phenomenon could be a consequence of current inadequate imaging of lymph node or bone metastasis or as a consequence subclinical metastatic spread remains undetectable during radical treatment. However, tumor biology itself could lead to the progression of the disease in the high-risk group. As a consequence, risk-adapted therapy is very important in these cases. The applied radiation dose plays an important role in radiotherapy. Several publications have shown that the biochemical relapse correlates with the generally accepted risk factors and the radiation dose. Regarding this, high-quality treatment planning and HDR brachytherapy combined with EBRT (external beam radiation therapy) leads to good treatment results in selected groups. So far in our own experience, HDR brachytherapy in combination with EBRT is a successful form of treatment with few acute and late side effects in the first 42 patients examined. First results concerning to PSA relapse-free time, quality of life, miction, and erectile function are promising.
Biomarkers, Tumor↗
[Association between classic cardiovascular risk factors and age-related maculopathy (ARM). Results of the baseline examination of the Münster Aging and Retina Study (MARS)].
BACKGROUND: Epidemiological studies have reported inconsistent associations between cardiovascular risk factors and the occurrence of age-related maculopathy (ARM). METHODS: In the baseline examination of the Muenster Aging and Retina Study (MARS), we assessed this potential relationship in 1060 subjects who underwent clinical and ophthalmologic examinations. The ARM status was graded according to international standardized classifications. RESULTS: There were 974 eye pairs available for analysis. Smoking, hypertension, hypercholesterolemia, and a history of myocardial infarction or stroke were found significantly more often in patients with ARM. There were no statistically significant multivariate associations between overweight, diabetes, or a history of myocardial infarction or stroke. CONCLUSIONS: Our results confirm previous epidemiological studies pointing to a potential role of atherosclerotic processes in the development of ARM.
Aged↗
[Visual function and quality of life in patients with age-related maculopathy: results of the Münster Age and Retina Study (MARS)].
BACKGROUND: The aim of this study was to examine the association between increasing severity of age-related maculopathy (ARM) stages, visual function and quality of life. METHODS: Using the 25-item version of the National Eye Institute Visual Function Questionnaire (NEI VFQ) in the Münster age and retina study (MARS), 974 patients (normal fundus: n = 208; early ARM: n = 466; late ARM: n = 300) with bilateral gradable fundus photographs were asked about their visual function and quality of life. The NEI VFQ scales with regard to general health, general vision, near vision, distance vision and peripheral vision were assessed. According to the ARM stages, age- and gender-adjusted mean scores were calculated and tested for statistically significant differences. RESULTS: The perception of general health, general vision, near vision, distance vision and peripheral vision was getting worse with increasing severity of ARM stages. Comparing the maculopathy groups, significant differences in age- and gender-adjusted mean scores were found between patients with late ARM and healthy subjects and patients with late and early ARM. Furthermore, we observed for the dimension general vision a significant difference of the mean score between early ARM and healthy control group [mean score; early ARM: 68.7 (0.7) vs. control group: 72.2 (1.1); p = 0.005]. CONCLUSIONS: The results of the NEI VFQ reflect the clinical expectation of an inverse relation between increasing severity of ARM stages and visual function and quality of life.
Age Factors↗
Evaluation of insulin-like growth factor II, cyclooxygenase-2, ets-1 and thyroid-specific thyroglobulin mRNA expression in benign and malignant thyroid tumours.
OBJECTIVE: We evaluated three markers (insulin-like growth factor II (IGF-II), cyclooxygenase-2 (COX-2) and ets-1) of thyroid growth stimulation and cell transformation together with a thyroid-specific marker (thyroglobulin (Tg)) for their potential to differentiate benign and malignant follicular thyroid neoplasia (FN). DESIGN AND METHODS: mRNA expression levels were determined by real-time PCR in 100 snap-frozen thyroid samples: 36 benign thyroid nodules with different histology and function (19 cold (CTN) and 17 toxic thyroid nodules (TTN)), 36 corresponding normal thyroid tissues of the same patients, eight Graves' disease (GD) thyroids, 10 follicular thyroid carcinomas (FTC) and 10 papillary thyroid carcinomas (PTC). RESULTS: Mean IGF-II and COX-2 levels were not significantly altered between benign and malignant thyroid nodules (IGF-II) or nodular (FTC, TTN, CTN) and normal thyroid tissues (COX-2). In contrast, eight- to tenfold upregulation of ets-1 was observed in PTC and three- to fourfold upregulation of ets-1 was observed in FTC (and GD) compared with benign thyroid nodules and normal thyroid tissues. In addition, thyroglobulin mRNA expression was markedly downregulated (50- to 100-fold) in FTC, PTC and GD samples compared with benign nodular and normal thyroid tissues. Hence an ets-1/Tg ratio >20 distinguished differentiated thyroid cancer from benign nodular or normal thyroid tissue. We then studied ets1- and Tg mRNA expression levels in fine needle aspiration cytology (FNAC) samples. However, in a consecutive series of 40 FNAC samples only equivocal results were obtained on 38 benign and two malignant (FTC) thyroid tumour samples. CONCLUSIONS: Upregulation of ets-1 and downregulation of Tg mRNA expression occur in differentiated thyroid cancer and may facilitate pre-operative identification of thyroid malignancy depending on further evaluation of these potentially promising markers in a larger series of benign and malignant thyroid tumours and their FNAC samples.
Adenoma↗
Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe.
Our aim was to determine the effects of carotid body denervation (CBD) on the ventilatory responses to focal acidosis and ibotenic acid (IA) injections into the medullary raphe area of awake, adult goats. Multiple microtubules were chronically implanted into the midline raphe area nuclei either before or after CBD. For up to 15 days after bilateral CBD, arterial PCO2 (PaCO2) (13.3 +/- 1.9 Torr) was increased (P < 0.001), and CO2 sensitivity (-53.0 +/- 6.4%) was decreased (P <0.001). Thereafter, resting PaCO2 and CO2 sensitivity returned (P <0.01) toward control, but PaCO2 remained elevated (4.8 +/- 1.9 Torr) and CO2 sensitivity reduced (-24.7 +/- 6.0%) > or =40 days after CBD. Focal acidosis (FA) at multiple medullary raphe area sites 23-44 days post-CBD with 50 or 80% CO(2) increased inspiratory flow (Vi), tidal volume (Vt), metabolic rate (VO2), and heart rate (HR) (P <0.05). The effects of FA with 50% CO2 after CBD did not differ from intact goats. However, CBD attenuated (P <0.05) the increase in Vi, Vt, and HR with 80% CO2, but it had no effect on the increase in VO2. Rostral but not caudal raphe area IA injections increased Vi, BP, and HR (P < 0.05), and these responses were accentuated (P <0.001) after CBD. CO2 sensitivity was attenuated (-20%; P <0.05) <7 days after IA injection, but thereafter it returned to prelesion values in CBD goats. We conclude the following: 1) the attenuated response to FA after CBD provides further evidence that the carotid bodies provide a tonic facilitory input into respiratory control centers, 2) the plasticity after CBD is not due to increased raphe chemoreceptor sensitivity, and 3) the "error-sensing" function of the carotid body blunts the effect of strong stimulation of the raphe.
Acidosis↗
[Münster age- and retina study (MARS). Association between risk factors for arteriosclerosis and age-related macular degeneration].
BACKGROUND: The association between arteriosclerosis and age-related macular degeneration (AMD) has only been examined in a few studies and the data is still very inconsistent. METHODS: A cross sectional study was initiated with 730 patients from the Münster age and retina study (MARS) which examines patients in the age range 60 to 80 years old who were referred by ophthalmologists from the Muenster area. Patients with narrow angle glaucoma were excluded. All patients underwent a standardized ophthalmoscopic examination und were classified into four groups: group 1 without AMD ( n=190), group 2 with unilateral or bilateral early forms of AMD ( n=340), group 3 with unilateral late forms of AMD ( n=139) and group 4 with bilateral late forms of AMD ( n=50). By means of these groups it was tested if there was a significant difference between the different risk factors for arteriosclerosis. RESULTS: The mean age was 72 years and 58% were women and the sex distribution within the different groups did not differ significantly (all trend tests with p>0.1). General risk factors for arteriosclerosis such as diabetes, body-mass-index and hypertension did not differ significantly (all trend tests with p>0.1). The number of smokers increased significantly with the severity of AMD ( p=0.02). Furthermore, various lipids were examined, adjusted for age and sex and showed significant decrease of HDL ( p=0.087) and significant increases of the HDL/LDL quotient ( p=0.0007) and the non-sober triglyceride values ( p=0.0058) correlated with the severity of AMD. CONCLUSIONS: There was a highly significant, direct association of indicators of dyslipidemia such as increasing HDL/LDL quotient and decreasing HDL with the severity of AMD. These results were underlined by increased triglyceride levels even if they were taken non-sober. The results must be interpreted with caution due to the explorative character of the evaluation.
Age Distribution↗
[Subjective determination of ocular refraction. I: Optical principles].
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Eyeglasses↗
[Subjective refraction assessment. II: Monocular fine adjustment].
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Accommodation, Ocular↗
[Determining subjective refraction. III: Binocular balance, near vision eyeglasses].
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Accommodation, Ocular↗
Model structure identification for wastewater treatment simulation based on computational fluid dynamics.
The objective of this presented project is to use the results of an CFD simulation to automatically, systematically and reliably generate an appropriate model structure for simulation of the biological processes using CSTR activated sludge compartments. Models and dynamic simulation have become important tools for research but also increasingly for the design and optimisation of wastewater treatment plants. Besides the biological models several cases are reported about the application of computational fluid dynamics ICFD) to wastewater treatment plants. One aim of the presented method to derive model structures from CFD results is to exclude the influence of empirical structure selection to the result of dynamic simulations studies of WWTPs. The second application of the approach developed is the analysis of badly performing treatment plants where the suspicion arises that bad flow behaviour such as short cut flows is part of the problem. The method suggested requires as the first step the calculation of fluid dynamics of the biological treatment step at different loading situations by use of 3-dimensional CFD simulation. The result of this information is used to generate a suitable model structure for conventional dynamic simulation of the treatment plant by use of a number of CSTR modules with a pattern of exchange flows between the tanks automatically. The method is explained in detail and the application to the WWTP Wuppertal Buchenhofen is presented.
Algorithms↗
Simulation of a nitrification control concept considering influent ammonium load.
Buchenhofen wastewater treatment plant of Wupperverband (650,000 p.e.) is currently being expanded for targeted nitrogen elimination. In view of the limited space available for extension, an optimized control concept is to be used in order to minimize the number of additional tanks required. This concept was investigated by dynamic simulation based on Activated Sludge Model No. 1. The investigations included a pure feedback control configuration and a configuration combining feedback und feedforward control, considering the influent ammonium load, for aeration. The results show that combined feedforward/feedback control has significant advantages over pure feedback control. In particular, this configuration allows a reduction in the effluent NH4-N peaks, which is especially important because of the low NH4-N limit of 5 mg NH4-N/L in a grab sample.
Computer Simulation↗
Expression of the cell cycle phosphatase cdc25C is down-regulated by the tumor suppressor protein p53 but not by p73.
The cdc25C phosphatase dephosphorylates cdc2 kinase which then in complex with cyclin B can catalyse transition from the G(2) phase to mitosis. We demonstrate that transcription of cdc25C is repressed by p53 in a dose-dependent manner. In stably transfected DLD-1 colorectal adenocarcinoma cells, cdc25C expression is down-regulated when p53 is induced from a (tet)-off-regulated system. In contrast to p53, its homologue p73 is not able to down-modulate cdc25C expression. A previously identified site in the cdc25C promoter can bind p53 in vitro and, when placed in a heterologous construct, is able to activate transcription. However, transcriptional repression by p53 is not mediated through this site but is dependent on a segment containing three CCAAT-boxes. In general down-regulation of cdc25C transcription by reducing the levels of active cdc2 kinase contributes to G(2) arrest and G(2)/M checkpoint control. This reveals functional differences between p73 and p53 in regulating cell division.
Animals↗
A stress-responsive glyoxalase I from the parasitic nematode Onchocerca volvulus.
Glyoxal, methylglyoxal and other physiological alpha-oxoaldehydes are formed by the lipid peroxidation, glycation and degradation of glycolytic intermediates. They are detoxified enzymically by the glyoxalase system. To investigate the physiological function of glyoxalase I in parasitic organisms, the cDNA for glyoxalase I from the filarial nematode Onchocerca volvulus (designated Ov-GloI) has been cloned and characterized. The isolated cDNA contains an open reading frame of 579 bp encoding a protein with a calculated molecular mass of 21930 Da. Owing to the high degree of sequence identity (60%) with human glyoxalase I, for which the X-ray structure is available, it has been possible to build a three-dimensional model of Ov-GloI. The modelled core of Ov-GloI is conserved compared with the human glyoxalase I; however, there are critical differences in the residues lining the hydrophobic substrate-binding pocket of Ov-GloI. A 22 kDa protein was obtained by heterologous expression in Escherichia coli. A homogeneous enzyme preparation was obtained by affinity purification and functional characterization of the recombinant enzyme included the determination of kinetic constants for methylglyoxal and phenylglyoxal as well as inhibition studies. Gel filtration demonstrated a dimeric structure. To assess the role of Ov-GloI as a potential vaccine candidate or serodiagnostic tool, the serological reactivity of the recombinant Ov-GloI was analysed with sera from microfilaria carriers and specific IgG1 antibodies were detected. The effects of oxidative insult, namely plumbagin and xanthine/xanthine oxidase, on the gene transcript level of Ov-GloI were investigated. By using a semi-quantitative PCR ELISA it was shown that Ov-GloI is expressed at elevated levels under conditions of oxidative stress.
Amino Acid Sequence↗
Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis.
Immunocompromised patients are at risk of developing toxoplasma encephalitis (TE). Standard therapy regimens (including sulfadiazine plus pyrimethamine) are hampered by severe side effects. While atovaquone has potent in vitro activity against Toxoplasma gondii, it is poorly absorbed after oral administration and shows poor therapeutic efficacy against TE. To overcome the low absorption of atovaquone, we prepared atovaquone nanosuspensions (ANSs) for intravenous (i.v.) administration. At concentrations higher than 1.0 microg/ml, ANS did not exert cytotoxicity and was as effective as free atovaquone (i.e., atovaquone suspended in medium) against T. gondii in freshly isolated peritoneal macrophages. In a new murine model of TE that closely mimics reactivated toxoplasmosis in immunocompromised hosts, using mice with a targeted mutation in the gene encoding the interferon consensus sequence binding protein, i.v.-administered ANS doses of 10.0 mg/kg of body weight protected the animals against development of TE and death. Atovaquone was detectable in the sera, brains, livers, and lungs of mice by high-performance liquid chromatography. Development of TE and mortality in mice treated with 1.0- or 0.1-mg/kg i.v. doses of ANS did not differ from that in mice treated orally with 100 mg of atovaquone/kg. In conclusion, i.v. ANSs may prove to be an effective treatment alternative for patients with TE.
Animals↗
A telephone needs assessment for potential high utilizers.
BACKGROUND AND OBJECTIVES: We conducted a telephone needs assessment of patients at risk for high utilization of health services to determine the type of intervention that might be most responsive to their needs. METHODS: Family practice patients who were classified as at high risk based on self-reported health-related quality of life (HRQOL), age, and gender received a structured telephone interview to ask about their health problems, difficulties with their health care, and types of help programs that might be useful to them. RESULTS: Of 867 adult patients randomly selected as eligible for the study, 352 completed the Duke Health Profile to measure HRQOL, 122 were classified at risk for high utilization, and 104 were interviewed by telephone. Patient-reported health problems were similar to provider-reported problems. High-risk patients reported difficulties receiving help from the clinic on issues of communication and logistics (43.9%), limitations of clinic facilities and services (26.3%), and financial concerns (26.3%). Of the highest risk patients, 45.8% expressed willingness to participate in help programs conducted over the telephone. CONCLUSIONS: Many high-risk patients might benefit from participation in a telephone intervention program. A future study is needed to measure the effectiveness of such a program to improve utilization of health services.
Adult↗