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C Heuer

Publications and source records attributed to C Heuer.

9 recordsLinked to original sources
PubMed1997

Modeling of time trends and interactions in vital rates using restricted regression splines.

For the analysis of time trends in incidence and mortality rates, the age-period-cohort (apc) model has became a widely accepted method. The considered data are arranged in a two-way table by age group and calendar period, which are mostly subdivided into 5- or 10-year intervals. The disadvantage of this approach is the loss of information by data aggregation and the problems of estimating interactions in the two-way layout without replications. In this article we show how splines can be useful when yearly data, i.e., 1-year age groups and 1-year periods, are given. The estimated spline curves are still smooth and represent yearly changes in the time trends. Further, it is straightforward to include interaction terms by the tensor product of the spline functions. If the data are given in a nonrectangular table, e.g., 5-year age groups and 1-year periods, the period and cohort variables can be parameterized by splines, while the age variable is parameterized as fixed effect levels, which leads to a semiparametric apc model. An important methodological issue in developing the nonparametric and semiparametric models is stability of the estimated spline curve at the boundaries. Here cubic regression splines will be used, which are constrained to be linear in the tails. Another point of importance is the nonidentifiability problem due to the linear dependency of the three time variables. This will be handled by decomposing the basis of each spline by orthogonal projection into constant, linear, and nonlinear terms, as suggested by Holford (1983, Biometrics 39, 311-324) for the traditional apc model. The advantage of using splines for yearly data compared to the traditional approach for aggregated data is the more accurate curve estimation for the nonlinear trend changes and the simple way of modeling interactions between the time variables. The method will be demonstrated with hypothetical data as well as with cancer mortality data.

Age Factors↗
PubMed1995

Occupation, smoking and demographic factors, and renal cell carcinoma in Germany.

BACKGROUND: The role of occupational exposure in the aetiology of renal cell cancer is still not clear. In a population-based, case-control study we investigated occupational and smoking history as well as place of residence, marital and socioeconomic status. METHOD: In a case-control study in Germany, 277 adult cases with incident renal cell cancer and 286 controls frequency-matched to the cases for age and gender have been interviewed. The data were analysed by standard methods using unconditional logistic regression models, to estimate the relative risk (RR) and the corresponding 95% confidence interval (95% CI). RESULTS: Socioeconomic status was inversely associated (RR = 0.61, 95% CI: 0.3-1.2 for highest category) with the risk for renal cell cancer. Heavy smoking gave an increased, but not significant (about twofold) RR in men and women for ex-smokers and current smokers. Employment in metal-related industries (RR = 1.63, 95% CI: 1.1-2.5) was also identified as a risk factor. Additionally, we found an elevated risk associated with exposure to perchloroethylene and tetrachlorocarbonate (RR = 2.52, 95% CI: 1.2-5.2) but no time trend could be observed. No associations were found for other occupational exposures, such as working in the chemical industry, transportation or farming nor for exposure to pesticides. CONCLUSIONS: The results of our study lead to the suggestion that smoking, occupation and demographic factors probably play a minor role in the aetiology of renal cell cancer.

Adult↗
PubMed1994

[Trend analysis in Hodgkin disease mortality in the German Federal Republic 1955-1989: a comparison of log-linear models with descriptive standard methods].

Age-Period-Cohort (APC) models have become a widely accepted method to analyse incidence and mortality rates of cancer or other diseases. In this paper we compare simple descriptive methods such as plotting age-specific rates and standardized rates with regression models in order to investigate mortality rates of Morbus Hodgkin's disease in Germany (West-Germany) between 1955 and 1989. With any of the approaches it can be seen that the mortality of Morbus Hodgkin's disease has been decreasing around 1970. Although APC-models allow some detailed investigation of the separate influence of the age, period and cohort effect, the results are difficult to interpret as there is no unique solution for the parameter estimates (identification problem of APC-models). For the mortality of Morbus Hodgkin's, the result of the APC-modelling shows that the decrease of mortality is overestimated if the cohort effect is not taken into consideration. We therefore conclude that the interpretation of the APC-model should be done in connection with other methods to avoid misinterpretation. The combination of both approaches will lead to a better understanding of the incidence or mortality patterns of cancer.

Adult↗
PubMed1993

Agitation, aeration and perfusion modules for cell culture bioreactors.

For an optimized bioreactor design which is adapted to the cultivation of sensitive animal cells different modular bioreactor components for gentle agitation, sufficient aeration and long-term perfusion were developed and investigated with respect to their suitability from laboratory to production scale. Aeration systems have been designed for both shear sensitive cells and cells which tolerate bubbles. The systems are based on either membranes for bubble-free aeration or stainless steel sparger systems. They were characterized by determination of their oxygen transfer capacity and optimized in cultivation processes of different cell lines under process conditions such as batch and perfusion mode. Different impellers for suspension cells and cells grown on carriers were investigated for their suitability to ensure homogeneous gentle mixing. A large pitch blade impeller as well as a novel 3-blade segment impeller are appropriate for homogeneous mixing at low shear rates. Especially with the 3-blade segment impeller fluid mechanical stress can be reduced at a given stirrer speed which is advantageous for the cultivation of cells attached to microcarriers or extremely shear sensitive suspension cells. However, our results indicate that shear sensitivity of animal cells has been generally overestimated. Continuous perfusion of both suspension cell cultures and cells cultivated on microcarriers could be successfully performed over extended periods of time using stainless steel spinfilters with appropriate pore sizes and systems based on microporous hydrophilic membranes. Spinfilters are suitable cell retention systems for technical scale bioreactors allowing continuous perfusion cultures of suspension cells (pore size 10 to 20 microns) as well as anchorage dependent cells grown on microcarriers (pore size 75 microns) over six weeks to 3 months. Applying the developed modules for agitation, aeration and perfusion process adapted bioreactor set-ups can be realized which ensure optimum growth and product formation conditions in order to maximize cell and product yields.

Air↗
PubMed1992

[Extragenital endometriosis with multiple stenoses of the small intestine].

This paper reports on the case of a 38-year-old woman with multiple stenoses in the proximal and middle section of the jejunum, as well as in the terminal ileum, who had been symptomatic for nine years, with symptoms progressively reflecting obstruction due to mechanical subileus. The cause was found to be extragenital endometriosis which, with the mucosa remaining intact, was associated with hormone-dependent bleeding with subsequent fibrosis leading to segmental thickening of the bowel wall and narrowing of the lumen. The diagnostic work-up included a radiological study of the small bowel as described by Sellingk, abdominal sonography and a CT exam; the X-ray study and the CT scan revealed stenosing of the bowel, while sonography and CT showed wall thickening. The treatment of this condition comprises resection of the affected bowel segment together with anti-estrogen treatment or ovariectomy, and in this respect differs notable from the more common Crohn's disease of the small bowel, from which it must be diagnostically differentiated.

Adult↗
PubMed1988

Tet repressor-tet operator contacts probed by operator DNA-modification interference studies.

Contacts between tet operator DNA and Tet repressor protein are characterized by modification interference studies. The modified DNA fragments are separated into fractions with high, intermediate and low affinities for Tet repressor by polyacrylamide gel electrophoresis. Ethylation of the phosphates with N-ethylnitrosourea reveals 12 contacts of a repressor dimer to tet operator. Eight of these contacts appear to be important for Tet repressor binding, as judged by the strong interference at these positions, while four contacts are probably less important. All of the phosphate contacts are located on the same side of the B-DNA structure. The sequences of tet operators proposed to interact with the recognition alpha-helix of Tet repressor are TCTATC in three cases and CCTATC in one case. After methylation of N-7 with dimethylsulfate, strong interference is observed at the guanine residues at positions +/- 2. None of the N-7 functions of other guanine residues seems to be involved in tight contacts to Tet repressor. Tet repressor subunits form identical phosphate and guanine N-7 contacts with each half side of the two tet operators indicating twofold dyad symmetry of the complexes. Attempts to analyze the methylation interference at the adenine N-3 sites reveal different results for the operators. Modification of DNA fragments with diethylpyrocarbonate yields hypersensitive sites in the tet operators, indicating different local DNA structures. Carbethoxylation interference studies confirm the contacts at the purines found by methylation interference. All of the sequence-specific protein-DNA contacts detected in this study are centered at the inside four base-pairs in each tet operator half side. The contacts are discussed with respect to the structure of the repressor-operator complex.

Autoradiography↗
PubMed1987

Constitutive expression of tetracycline resistance mediated by a Tn10-like element in Haemophilus parainfluenzae results from a mutation in the repressor gene.

The Tn10-like constitutively expressed tetracycline resistance determinant from a Haemophilus parainfluenzae strain was cloned in Escherichia coli. Toxicity resulting from expression on multicopy plasmids necessitated its being cloned on a low-copy plasmid vector or in cells containing the Tn10-encoded repressor. Constitutive expression of tetracycline resistance was found to result from the synthesis of a truncated inactive repressor molecule. Instead of the 23-kilodalton repressor found in other Tn10-containing strains, this determinant encoded a 14.5-kilodalton molecule. The DNA sequence of the 700-base-pair region spanning the repressor gene and promoter-operator regions of the Haemophilus determinant was identical to that of the same region of Tn10, except for the absence of a single T X A base pair in the repressor gene. This deletion leads to premature termination of the protein. Antisera to the repressor suggested that the repressor was also absent in a second independently isolated H. parainfluenzae strain bearing a Tn10-like constitutive tetracycline resistance determinant.

Cloning, Molecular↗