[The future incidence of colorectal and lung cancers: results of the calculation of different scenarios for the year 2020]. / Die künftige Entwicklung der Erkrankungszahlen von Darmkrebs und Lungenkrebs : Ergebnisse der Berechnung verschiedener Szenarien für das Jahr 2020.

BACKGROUND: Cancer is a common disease that places a large burden on health-care systems. Although the rise of incident cancer cases over recent decades in Germany can largely be explained by demographic ageing, other factors also affect these numbers. The aim of this work was to calculate the incidence of colorectal and lung cancers, two of the most common cancer sites, for the year 2020 under different scenarios. MATERIALS AND METHODS: The calculations were based on national incidence estimates by the Centre for Cancer Registry Data at the Robert Koch Institute. Two scenarios were calculated for each of the two cancer sites and by gender. The "status quo" scenario accounts only for demographic ageing, assuming constant age-specific incidence rates. The second scenario additionally assumes that trends in incidence rates observed from 2000 to 2009 continue up to the year 2020. RESULTS: The "status quo" scenarios showed an increase in incident cancer cases of between 12 and 24%, depending on gender and cancer site. The "continuing trends" scenarios resulted in smaller increases for colorectal cancer (+3 to + 17%), while the results for lung cancer differed widely between women (+ 64%) and men (+ 2%). In general, large increases are expected for the highest age groups and the age groups of the baby boomer generation. DISCUSSION: Changes in the age structure of the German population will lead to an increase in incident cancer cases and a higher portion of geriatric patients. Additionally, further increasing incidence rates would result in a dramatic growth in the number of female lung cancer patients.

[Nationwide statements from regional data: methods of the Center for Cancer Registry Data]. / Von regionalen Daten zu bundesweiten Aussagen : Die Methoden im Zentrum für Krebsregisterdaten.

Despite having achieved nationwide registry coverage in addition to substantial improvements in data on the epidemiology of cancer in Germany, the Centre for Cancer Registry Data continues to estimate national statistics on incidence, survival, and prevalence instead of calculating these directly from available data. The methods used for evaluations are based initially on estimates of registration completeness or, for survival analyses, an assessment of the quality of follow-up data. The completeness of incident case registration is estimated on the basis of the mortality/incidence procedure, which assumes a largely constant relationship between the mortality and incidence of a cancer type among people of the same age and sex across federal states. Inclusion criteria for consideration of registry data in national survival analyses are less than 15% of death certificate only (DCO) cases and plausible survival for patients with pancreatic cancer or metastatic lung cancer. Of the 477,300 incident cancer cases estimated for 2010, 429,900 were reported by the cancer registries (90%), and ten federal states contributed data to national survival estimates.

[The (German) Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI) in Berlin]. / Das Zentrum für Krebsregisterdaten (ZfKD) im Robert Koch-Institut (RKI) in Berlin.

Cancer represents the second most common cause of death in Germany. The country's federal states operate regional population-based cancer registries that collect and analyze data on cancer patients. This provides an essential basis for describing the cancer burden in the German population. In order to obtain valid and reliable information on cancer incidence at the national level, the Robert Koch Institute (RKI) set up the Federal Cancer Surveillance Unit in 1983 as a central institution for evaluating this cancer registry data. In August 2009, when the Federal Cancer Registry Data Act (BKRG) came into force, the Center for Cancer Registry Data (ZfKD) at the RKI took over the work of the Cancer Surveillance Unit with a broader remit. In the future, it will also regularly publish findings on survival, prevalence, and tumor stage distribution. A newly established record linkage process will help identify multiple submissions from the federal states. Further innovations and new tasks of the ZfKD include expanding an interactive Internet platform and encouraging a more intensive use of cancer registry data for epidemiological research by providing datasets to external scientists. The range of information available to the interested public is also to be expanded.

Recombinant expression and domain structure of the Rna1 protein from Schizosaccharomyces pombe.

The amino acid sequence of Rna1p, a yeast protein implicated in the maturation and/or nucleocytoplasmic transport of RNA, is characterised by the presence of eight leucine-rich repeats (LLRs) as well as two intervening repeats of a different type and a highly acidic C-terminal region. Limited proteolysis of purified Rna1p expressed recombinantly in bacteria reveals that the C-terminal extension but not the region containing the two types of repeats is highly accessible to proteolytic attack and that the C-terminal region most likely harbours (a) low affinity Ca(2+)-binding site(s). These results are indicative of the domain structure of the Rna1p molecule, with the repeats and the C-terminal region being accessible for different interactions.

Laser secondary neutral mass spectrometry for copper detection in micro-scale biopsies.

Disease progression and clinical diagnostics of a number of hereditable metabolic diseases are determined by organ involvement in disturbed deposition of certain molecules. Current clinical imaging is unable to visualize this maldistribution with sufficient specificity and sensitivity, such as in Wilson's disease. The quest for understanding cellular Cu distribution in these patients requires element- and molecule-specific images with nanometer-scale spatial resolution. We have used a new cryo-mass spectrometric instrument with an integrated cryosectioning chamber for preparation and analysis of frozen hydrated samples of Wilson's disease tissue. With laser post-ionization secondary neutral mass spectrometry (laser-SNMS), we were able to image Cu and other intrinsic elements and molecules in less than 1 mg of frozen hydrated liver tissue from a murine model of Wilson's disease. A 40-50 times higher Cu concentration was measured in the disease tissue as compared to the control mouse. Furthermore, major histomorphological changes were observed using this advanced nano-science tool. The results showed that the combination of in-vacuum cryosectioning and cryo-laser-SNMS technologies is particularly well suited for identifying specific cell structures and imaging trace element concentrations with subcellular resolution and upper-parts-per-billion sensitivity in biological samples. This technology can provide a novel diagnostic tool for clinical applications in various diseases involving trace elements.

[Future cancer incidents in Germany]. / Die zukünftige Entwicklung des Krebsgeschehens in Deutschland.

The future as well as the past development of cancer incidents in Germany is of continuous importance for health policy. Cancer incidence data observed over more than 20 years are analysed by log-linear models with polynomial trend components. The estimated trend models are used for a trend extrapolation until the year 2020. Since cancer registration in Germany is not complete yet and does not cover the whole area of the country national incidences are estimated by the data of the existing complete regional cancer registries. In this way it can be assessed that the number of new cancer diseases increased from 270,000 cases in 1980 to 420,000 cases in 2002. Extrapolating the trends and taking into account the demographic prognosis of the German Federal Statistical Office 570,000 (version 1) or 590,000 (version 9) annual cancer cases are predicted for the year 2020. From 1980 to 2002 a decrease of cancer mortality was observed. If this trend continues until 2020, the number of deaths caused by cancer would decrease from 209,000 in 2002 to 153,000 (or 158,000) in 2020, although the number of cancer cases are predicted to increase. Assuming constant mortality rates the number of deaths caused by cancer would be much higher.

Conserved charged residues in the leucine-rich repeat domain of the Ran GTPase activating protein are required for Ran binding and GTPase activation.

GTPase activating proteins (GAPs) for Ran, a Ras-related GTPase participating in nucleocytoplasmic transport, have been identified in different species ranging from yeast to man. All RanGAPs are characterized by a conserved domain consisting of eight leucine-rich repeats (LRRs) interrupted at two positions by so-called separating regions, the latter being unique for RanGAPs within the family of LRR proteins. The cytosolic RanGAP activity is essential for the Ran GTPase cycle which in turn provides directionality in nucleocytoplasmic transport, but the structural basis for the interaction between Ran and its GAP has not been elucidated. In order to gain a better understanding of this interaction we generated a number of mutant RanGAPs carrying amino acid substitutions in the LRR domain and analysed their complex formation with Ran as well as their ability to stimulate the intrinsic GTPase activity of the G protein. We show that conserved charged residues present in the separating regions of the LRR domain are indispensable for efficient Ran binding and GAP activity. These separating regions contain three conserved arginines which could possibly serve as catalytic residues similar to the arginine fingers identified in GAPs for other small GTPases. However, mutations in two of these arginines do not affect the GAP activity and replacement of the third conserved arginine (Arg91 in human RanGAP) severely interferes not only with GAP activity but also with Ran binding. This indicates that RanGAP-stimulated GTP hydrolysis on Ran does not involve a catalytic arginine residue but requires certain charged residues of the LRR domain of the GAP for mediating the protein-protein interaction.

[The Lee-Carter model of the prognosis of mortality in Germany. Berlin Public Health Research Group--partial project "Goals and Goal Indicators for Public Health in East and West Berlin"]. / Das Lee-Carter-Modell zur Prognose der Sterblichkeit in der Bundesrepublik Deutschland. Berliner Forschungsverbund Public Health (BFPH)--Teilprojekt "Ziele und Zielindikatoren für den Gesundheitsbereich in Berlin Ost und West".

A model for forecasting mortality developed by Lee and Carter is applied to data of West Germany. The logs of the age-specific death rates are modeled as a linear function of an unobserved mortality index using the singular value decomposition method. The forecasts are based on projections of all individual trends of the mortality rates. Applied to life expectancy at birth between 1969 and 1992 the model implies an increase of 2.2 years in life expectancy for men and 2.4 years for women in 2002.

The acidic C-terminal domain of rna1p is required for the binding of Ran.GTP and for RanGAP activity.

The small GTP binding protein Ran is an essential component of the nuclear protein import machinery whose GTPase cycle is regulated by the nuclear guanosine nucleotide exchange factor RCC1 and by the cytosolic GTPase activating protein RanGAP. In the yeasts Schizosaccharomyces pombe and Saccharomyces cerevisiae the RanGAP activity is encoded by the RNA1 genes which are essential for cell viability and nucleocytoplasmic transport in vivo. Although of limited sequence identity the two yeast proteins show a conserved structural organization characterized by an N-terminal domain of eight leucine-rich repeats, motifs implicated in protein-protein interactions, and a C-terminal domain rich in acidic amino acid residues. By analyzing the RanGAP activity of a series of recombinantly expressed rna1p mutant derivatives, we show that the highly acidic sequence in the C-terminal domain of both yeast proteins is indispensable for activating Ran-mediated GTP hydrolysis. Chemical cross-linking reveals that the same sequence in rna1p is required for rna1p.Ran complex formation indicating that the loss of GAP activity in the C-terminally truncated rna1p mutants results from an impaired interaction with Ran. The predominant species stabilized through the covalent cross-link is a rna1p.Ran heterodimer whose formation requires the GTP-bound conformation of Ran. As the acidic C-terminal domain of rna1p is required for establishing the interaction with Ran, the leucine-rich repeats domain in rna1p is potentially available for additional protein interactions perhaps required for directing a fraction of rna1p to the nuclear pore.

[Frequency analysis for promoting public health goals--III: Potential abbreviation of longevity]. / Häufigkeitsanalytik für die Erarbeitung von Gesundheitszielen--Teil III: potentielle Lebenszeitverluste.

The article presents different mathematical algorithms intending to quantify the "potential years of life lost" based on life table models, and on real age-structured populations, respectively. Applying these algorithms to accident and cardiovascular mortality data from Berlin (West) demonstrates their individual and specific relevance.

["Public health goals"--concepts this side of utopia? Berlin Public Health Research Organization--divided project "Goals and goal indicators for East and West Berlin Public Health"]. / "Gesundheitsziele"--Konzepte diesseits von Utopien? Berliner Forschungsverbund Public Health (BFPH)--Teilprojekt "Ziele und Zielindikatoren für den Gesundheitsbereich in Berlin Ost und West".

Objectives or targets for health have been presented by the World Health Organisation as well as a number of national health administrations. Health objectives are intended as guidelines attracting the commitment of decision makers and health professionals. As a "normative health indicator" a health objective should quantify the desired progress and give the time by which it could be attained. The article discusses general and methodical aspects which are thought to be relevant in identifying and quantifying health objectives for a population.

[Cancer incidence estimates for Germany via log-linear models]. / Krebsinzidenzschätzungen für Deutschland mittels log-linearer Modelle.

In Germany presently no nationwide cancer registration exists. To estimate national cancer incidence, Poisson regression models were fitted to incidence/mortality ratios using age and sex specific data of the cancer registry of Saarland, Germany and were then applied to national mortality. The models estimate the absolute number of incident cases at a given point in time and moreover allow the assessment of time trends. Applied to nationwide mortality the models imply a total of 347,000 new cancer cases in Germany for 1998 with 179,000 females and 168,000 males. During the nineties the age-standardised rate (European standard) has slightly decreased for males and slightly increased for females.

[The significance of AIDS for mortality in Berlin (West)]. / Die Bedeutung von AIDS für die Sterblichkeit in Berlin (West).

Following a long-term decline, death rates due to infectious diseases in West-Berlin men have dramatically increased since 1983. The Berlin mortality statistics introduced AIDS as a specific cause of death only in 1989. However, opportunistic infections, a negligible quantity until 1983, and pointing to AIDS as the underlying cause, show a steep increase in the mid and late eighties. In terms of Potential Years of Life Lost, AIDS-related mortality amounts to 8 percent of total mortality in West-Berlin men in 1989/1990.

[Frequency analysis for achieving health goals--II: Analysis of mortality tables for cause of death, expected mortality]. / Häufigkeitsanalytik für die Erarbeitung von Gesundheitszielen--Teil II: Sterbetafelanalytik von Todesursachen, Sterbeerwartungen.

The article gives algorithms to calculate mean ages at death for specific causes, based on life table models. Parameters of interest are death due to a specific cause, dying after the "elimination" of the specific cause, or the transition into a "new" structure of mortality when a specific cause of death vanishes. The setbacks of widely used calculations are discussed in this context. These different approaches are demonstrated by means of data pertaining to accident and cardiovascular mortality of the male population of Berlin (West). The estimated impact on life expectancy varies according to both the mathematical model and the specific cause of death: differences are negligible in mortality due to accidents, whereas the results differ considerably in cardiovascular causes of death. The algorithm suggested allows to constrain the calculations to specific age groups. Topics such as "avoidable death" and "health objectives" have to be aware of these different methods.

[Malignant melanoma in an ovarian dermoid cyst]. / Melanoma maligno en un quiste dermoide de ovario.

A case of patient that during a cesarean section, a dark zone of the Omentum was biopsied, and informated as melanosis. Then appeared a cystic mass in the left ovary, and an ooforectomy was performed, resulting a Primary Malignant melanoma.

[Frequency analysis for achieving health goals--I: Standardization]. / Häufigkeitsanalytik für die Erarbeitung von Gesundheitszielen--Teil I: Standardisierung.

The formal mathematical steps of direct and indirect standardisation are deduced and it is pointed out that standardisation is an analytical concept for processing data within the framework of structurised populations to enable correct interpretation of these data in a manner modified according to specific problems. In particular, this concept is not confined to transforming age-structured mortality data of a population to the age distribution of the members of a larger population by means of a rule of three. Standardisation is in fact a model of the macrolevel (population). It makes no demands on the modalities of structuring. The structure selected as standard is arbitrarily set. With time series, standardisation usually modifies only the levels of the figures and not the frequencies. The results of standardisation are in every case valid only if the standard is also stated. A rule of thumb is: In retrospective analysis it is meaningful to standardise on the structure at the beginning or end of the time series; in extrapolations standardisation should be performed on the last structure that had been determined, whereas for comparisons a median structure should be standardised. The standardisation approach can be used in case of weighted arithmetic, geometric or harmonic means. Before effecting standardisation, the type of connection between the employed data should be examined. The examples of concepts of direct standardisation refer to cardiovascular and accident mortality in West Berlin from 1963 to 1991, whereas those of indirect standardisation are based on the accident mortality in West Berlin in 1987 structured according to city districts.

[Federal Cancer Reporting Unit. Surveillance program for cancer registration in Germany]. / Die Dachdokumentation Krebs. Eine Surveillance-Einrichtung der Krebsregistrierung in Deutschland.

For 20 years the Federal Cancer Reporting Unit has been processing and analyzing the comprehensive data of the population-based cancer registries in the Federal Republic of Germany. For this purpose the registries transfer their epidemiological records that have been made anonymous to the Federal Cancer Reporting Unit in the Robert Koch Institute once a year. An essential task of the Federal Cancer Reporting Unit is to check the data coherence and especially the completeness of cancer registration. The completeness of registration is estimated by site- and register-specific log-linear models. Based on data from sufficiently complete registries, national incidence rates and their time trends are estimated. Cancer survival rates, lifetime, and age-conditional probability of developing cancer and risk of dying from cancer are calculated and interpreted. The results are published regularly. With increasing completeness of registration, multiple notification of cases in different registries and their exclusion by matching procedures becomes more important. With increasing completeness of registration, further problems can be addressed such as the incidence of rare cancer sites or the analysis of regional patterns of cancer incidence and their underlying causes. Given the different legal requirements of cancer registration in the federal states of Germany, a national institution such as the Federal Cancer Reporting Unit in the Robert Koch Institute, which is not directly involved in cancer registration, can perform these activities best.

Diastereoselective synthesis of optically active (2 R,5 R)-hexanediol.

Diastereoselective reduction of diketones with Lactobacillus kefir DSM 20587 was examined. The reduction of both oxo-functions proceeded highly diastereoselectively. (2 R,5 R)-Hexanediol 3 was produced starting from (2,5)-hexanedione 1 in quantitative yields with enantiomeric excess >99% and diastereomeric excess >99%. The reaction conditions were optimized: maximum yield of (2 R,5 R)-hexanediol was reached at pH 6, 30 degrees C and with equal amounts of substrate and cosubstrate. The applicability of the system in fed-batch experiments was demonstrated. The feed specific biomass concentration required to reach maximal yield and selectivity in fed-batch mode was determined.