bluuebunny/crossref_metadata_2025 huggingface dataset:
Zwischen Arbeitslosigkeit und Berufsverbot: Die deutschsprachige Ärzte‐Emigration nach Palästina 1933–1945
Authors: Kröner Hans‐Peter
Published: October 2006

When the National‐Socialists started their restrictive measures against Jewish civil servants and professionals in 1933, they caused a wave of emigration only to be surpassed by the one following the Anschluß of Austria and the ‘November pogrom’ in 1938. Due to their great number, jewish doctors were to become the main object of Nazi persecution in the professional group. Up until 1935 Palestine was their main destination of immigration. In 1935 the British Mandatory Government passed a numerus clausus which mainly cut down the licensing of newly arrived doctors. The article deals with the social problems caused by the mass immigration of a highly qualified professional group in Palestine and with the fight against the restrictive measures of the mandatory Government. A short retrospective glance is cast at the situation in Palestine before 1933. Finally an outlook is given at the impact of this immigration on the health system in Israel.
EURATOM, ENEA und die nationale Kernenergiepolitik in Deutschland
Authors: Stamm‐Kuhlmann Thomas
Published: October 2006

EURATOM was created by politicians who put the advancement of European integration above all other goals. However, the science and energy policies of the individual member states were still largely conceived within a national framework. After its official establishment, EURATOM began to develop a life of its own. Significant conflicts arose between national and EURATOM interests as the records of the German Foreign Office and the German Ministry of Atomic Energy demonstrate. German scientists, engineers and business leaders preferred the more liberal approach to the development of nuclear energy taken by OEEC and its affiliate, the European Nuclear Energy Agency ENEA. In conjunction with the IAEA in Vienna, however, EURATOM performed a particularly useful service in helping to control the proliferation of fissionable material.
Physikalische Prinzipien und praktischer Maschinenbau im industriellen Zeitalter
Authors: Zweckbronner Gerhard
Published: October 2006

In the case of technical sciences the question about interrelation of science and engineering refers to at least two aspects: What kind of interrelation does exist between natural sciences and engineering and between technical sciences and engineering? This paper brings into focus how technical sciences transform physical principles for to apply them to practical engineering. However, technical sciences do not only transform physical principles, and engineering is not merely applied natural science. On the contrary technical sciences have their autonomous subjects and methods of investigation.
Der Organismus im Spiegel physiologischer Forschungen und diagnostischer Verfahren
Authors: Lohff Brigitte
Published: October 2006

For a century and a half medicine depended increasingly on graphic registration methods and clinical images. Technical developments were not the only condition for that. In the middle of the 19th century the scientists got another perspective of their research‐object — the organism. This concept of an experimental and more physical medicine led to the idea, that the graphic curve registrated by an apparatus was identical with the inner organic processes. Consequently, connected with this principle of visualization, the diagnostic and the therapeutic strategies were influenced, and also the comprehension of illness.
Die Entdeckung des Unbewußten um 1900: Wissenschaftshistorische Anmerkungen zu Sigmund Freud
Authors: Schott Heinz
Published: October 2006

The Discovery of the Unconscious by Henri F. Ellenberger has become a common topic in the historiography of (dynamic) psychiatry. But many users of this term have still the opinion that Sigmund Freud was the unique discoverer. In reality there was a scientific context at the fin de siècle, which corresponded intensively with Freud's original concepts and formed their implications (e.g. Darwinism, Neurophysiology). Besides well‐documented synchronic analogies Freud implanted diachronic traditions within his psychoanalytic theory. Especially, his main work The Interpretation of Dreams implies Greek mythology as well as natural philosophy of romanticism. Freuds special concepts like ‘transfer’ and ‘resistance’ have to be analysed as historical metaphors.
Die Verlegung der Berliner Sternwarte nach Babelsberg — ein konservativer Neubeginn
Authors: Dick Wolfgang R.
Published: October 2006

In 1913 the Berlin Observatory was moved from the center of the city to Babelsberg on the outskirts of Berlin, now part of Potsdam. The new observatory was considerably larger in size and with respect to its staff, and it had got a completely new equipment. At that time it was the most modern astronomical observatory in Germany and possibly even in Europe. However, the scientific results achieved afterward were not comparable to that of other institutions, especially in the USA. A main reason was the conservative concept for the observatory, drawn up by Wilhelm Foerster and his colleagues, and restricting the work to classical fields of astronomy. Foerster's successor Hermann Struve tried to follow rather strictly this concept as well as the traditions of his family of astronomers. This led to conflicts with his collaborators Eugen Goldstein, Erwin Finlay Freundlich and Paul Guthnick, who were interested rather in astrophysics than in the classical problems.
Laplace schreibt nach Gotha
Authors: Brosche Peter
Published: October 2006

Around 1800, Laplace had an intense correspondence with his colleagues in Gotha on problems in celestial mechanics, especially on the lunar theory. Most of these letters are not included in Roger Hahn's New calendar of the correspondence of P. S. Laplace (1994).
Die Konstruktion von Vorläufern in der Wissenschaftsgeschichtsschreibung. Bemerkungen zu einer Fiktion
Authors: Andresen Marc
Published: October 2006

My initial exposition will reveal that the construction of precursors is a natural result within the framework of a descriptive, academic recording of historical facts. During this process, we assume the underlying supposition that academic terms, paradigms, schools of thought etc. are engendered independent of prevailing ‘historical fields of experience’. Finally, considering settlement archaeology and its concepts as established in the 19th and 20th centuries, I attempt to show that paradigms come into being in the process of distinct ‘historical fields of experience’ and thus that there is no such a thing like precursors.
Wissenschaftsförderung durch Reiseförderung. Reiseunterstützungen als Mittel der Forschungsförderung am Beispiel Bayerns im 19. Jahrhundert
Authors: Smolka Wolfgang J.
Published: October 2006

Early 19th century Bavarian state and its scientific institutions were not able to enforce important scientific enterprises and expeditions out of Europe like other European states did. Except the zoological, anthropological and mostly botanical researches of the Bavarian naturalists Spix and Martius (1817‐1820), who accompanied an Austrian expedition to Brazil enabled through the support of the first Bavarian king Maximilian I. Joseph, caused some attention by the international scientific community. The results of this expedition determined in certain ways the further scientific development in Bavaria during several decades. Another remarkable attempt to strengthen scientific progress by the financial support of explorations and expeditions since 1850 traced back to king Maximilian II., who tried to push Bavaria into a leading position among the middle european states just in the matters of science. The death of Maximilian II. in 1864 caused a big lack in supporting scientific enterprises up to the turn of the century. At the earliest in that time other institutions and social forces were able to take over this charges.
Das Reisen ist des Chemikers Lust ‐ auf den Spuren Robert Bunsens. Zu Robert Wilhelm Bunsens 100. Todestag
Authors: Krafft Fritz
Published: October 2006

The article deals with an aspect of the famous German chemist Robert Bunsen which has not been of much notice so far: his journeys. During his stay in Heidelberg (from 1852 on) Bunsen journeyed up to four months a year. Up to the age of seventy‐eight, he travelled twice almost every year either in spring or autumn when there were no lectures at the university. He made his journeys for reasons of pleasure and in need of rest from teaching and research. In the 19th century such frequency of travelling was quite unusual even for a bachelor like Bunsen. Beeing an enthusiastic wayfarer Bunsen also travelled far away often, so for example to Italy twelve times (even to Sicily), four times to Scotland and England, and twice to Mallorca. ‐ Bunsen's first nine week journey to Italy in 1843 disappointed him as to its scientific outcome. This journey was a turning‐point since he had travelled before for scientific purposes only, beginning with the postdoctoral trip which Bunsen took 1831/32 (sponsored by his sovereign, the king of Hannover) to Berlin, Paris and Vienna for education and information matters. The article sets this journey as well as subsequent travels focusing on science (information, professional communication, experimental team‐work) in the framework of continuing academic training. In the end of the 18th and in the 19th century such journeys for further academic education were mainly done at public expense by chemists and geologists as well as by mining and steel scientists to prepare and qualify themselves as either university professors or administrators for mining metallurgical industry. All these various forms of travelling (postdoctoral educational travels at public expense, scientific journeys, meetings for experimental team‐work, expeditions, and recreational trips) served the communication within the scientific community. No one who wanted to belong to this community was able to escape such form of communication.
Von der Vaterschaftsbestimmung zum Rassegutachten. Der erbbiologische Ähnlichkeitsvergleich als ‚österreichisch‐deutsches Projekt’︁ 1926‐1945
Authors: Kröner Hans‐Peter
Published: October 2006

The anthropological paternity test basing on a comparative examination of resemblances between a presumptive father and the child was developed in a ‘joint venture’ by Austrian and German anthropologists. After the Nazi rise to power the test was more and more abused to clarify questions of ‘dubious Aryan descent’ whereas in Austria its original function was retained until Austria's annexation by the German Reich. Then Austrian anthropologists too rushed to offer their services to the National Socialist racial legislation. The author shows that accusations by German state officials of the Austrian anthropologist rendering to many expert opinions in favour of the Jewish population, a legend repeated after the war, cannot be upheld any longer.
Geographischer und astrologischer Zonenbegriff in der Antike
Authors: Hübner Wolfgang
Published: October 2006

The five (or seven) zones are treated during Greek‐Roman antiquity in geography and theoretical astrology as well. Although there is no use of them in astrological prognostication, they occur in the ascending scale of the twelve planetary houses. The common planetary order (moon ‐ Mercury ‐Venus ‐ sun ‐ Mars ‐ Jupiter ‐ Saturn) owes its widespread success primarily to its symmetry on both sides of the central sun, but the twofold vertical mesotes‐pattern in the heaven seems to be invented according to the horizontal symmetry of the five geographical zones surrounding the terrestrial equator.
Wissenschaftsgeschichte mit oder ohne System? Ein methodologischer Rückblick auf das DFG‐Projekt Wissenschaftsgeschichte der Germanistik im 19. Jahrhundert
Authors: Ries Thorsten
Published: October 2006

Among the more recent developments in the historiography of the sciences accounts involving the systems theory by Niklas Luhmann have shown quite prolific in terms of published results and sources. The article investigates the hold of the theoretical grounds of systems theory for the several applications in the field of the history of German literary Scholarship, i. e. the Germanistik, and for this reason expands on the related project conducted by the German Research Society (DFG). In the course of this examination several cruces of theory transfer, especially concerning systems theory towards historiography, will be addressed, such as a deficit in operational application, the essentially ahistoric design of systems theory and its questionable inherent presuppositions on the processes of science.
Structure–activity relationship studies of a series of peptidomimetic ligands for α4 β1 integrin on Jurkat T‐leukemia cells
Authors: Liu Ruiwu , Peng Li , Han Huijun , Lam Kit S.
Published: October 2006

α4β1 integrin is a therapeutic target for inflammation, autoimmune diseases, and lymphoid cancers. A series of peptidomimetic ligands based on the Nle‐D‐I motif have been synthesized and their binding affinities (IC50) to activated α4β1 integrin on Jurkat T‐leukemia cells have been determined using a cell adhesion assay. One of the 51 ligands, 18, has been determined to have an IC50 of 0.6 nM and has a more than twofold increase of binding affinity than the initial lead compound 1. Extensive SAR studies provide important information for further ligand optimization, which has served as a foundation for studies that ultimately led to identification of a potent ligand with an IC50 of 2 pM. © 2006 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 595–604, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
The influence of diuretics on the excretion and metabolism of doping agents part iv—caffeine
Authors: Delbeke F. T. , Debackere M.
Published: October 2006

The urinary excretion of caffeine in humans was followed over a period of 36 h after the oral administration of ANIMINE®, a formulation containing caffeine‐α‐naphthylacetate.

The excretion of caffeine was not as markedly affected by the urinary pH as was found with stimulant amines. Excretion peaks were obtained 1‐2 h after the ingestion and the total amount of unchanged caffeine excreted during 12 h varied from 0.57 to 1.51 per cent.

The ingestion of the diuretics acetazolamide or furosemide 2 h after caffeine resulted in a urine‐flow dependent and consequently increased caffeine excretion during 2–4 h post‐diuretic. This increase paralleled the increase in urine volume resulting in no meaningful differences in caffeine concentration compared to normal conditions.
Pharmacokinetics of indoramin and its 6‐hydroxylated metabolite after repeated oral dosing
Authors: Pierce D. M. , Franklin R. A. , Warrington S. J.
Published: October 2006

The pharmacokinetics of indoramin and its active 6‐hydroxylated metabolite have been studied in healthy male volunteers after repeated oral dosing with 37.5 mg twice daily for 2 weeks. Plasma concentrations of indoramin accumulated, on average, three to four‐fold above those anticipated on the basis of the kinetics after the first dose, though steady state was achieved by the end of the first week and no further increase was observed after 2 weeks. The degree of accumulation was consistent between subjects, with a highly significant (p < 0.001) correlation between the concentration 2 h after a single dose and the average steady‐state concentration. Possible explanations for the accumulation of indoramin are discussed. Plasma concentrations of 6‐hydroxyindoramin, in contrast, did not accumulate on multiple dosing. At steady state, concentrations of the metabolite, as represented by the AUC0–8h, were approximately 30–40 per cent of those of the unchanged drug. Since the two compounds are approximately equipotent the metabolite may accounts for 25 per cent of the hypotensive activity of indoramin during a typical clinical regime of 37.5 mg twice daily.
Influence of a standard meal on the absorption of a controlled release pseudoephedrine suspension
Authors: Graves D. A. , Wecker M. T. , Amsel L. P. , Hinsvark O. N. , Bhargava A. K. , Rotenberg K. S. , Meyer M. C. , Straughn A. B.
Published: October 2006

The influence of a standard meal on the extent and rate of absorption of pseudoephedrine from a liquid controlled release (CR) formulation (Pennkinetic System) was studied in 16 normal male volunteers. Equivalent single doses of an immediate release reference syrup (IR‐Sudafed) and the CR suspension were each studied under both fasted and postprandial conditions. AUC results showed no significant influence of food or formulation, indicating that the CR formulation was absorbed to the same extent as the IR product under all conditions. CMAX and TMAX tabulations under fasted conditions indicated that the CR preparation peaked at a lower level at a later time. Food diminished IR CMAXs but the CR suspension's CMAXs and TMAXs were apparently unaffected by food. This study indicates that this CR pseudoephedrine suspension releases drug independently of food intake.
Plasma levels, heart rate, and blood pressure after intravenous, oral, and aerosol administration of reproterol in man
Authors: Hageman R. J. J. , De Zeeuw R. A. , Greving J. E. , Krann J. J. , Koëter G. H.
Published: October 2006

Three healthy volunteers received single doses of reproterol (D 1959) by means of intravenous infusion, oral and aerosol application, respectively. Administrations were separated by at least 1 week. Plasma levels were measured by means of high performance liquid chromatography.

After infusion, plasma levels showed a steep decline, indicative for a rapid distribution. Even though relatively large amounts of drug were given (up to 540 μg), this phenomenon caused reproterol levels to drop to values near or below the limit of reliable quantitation (1 ng ml−1) within 60 to 90 min. After oral administration of one or two tablets (containing 20 mg reproterol. HC1 per tablet), a very short lag time could be observed, indicating fast absorption. After one tablet, plasma level maxima (of plateau‐type) were 5.6 ng ml−1 and 2.3 ng ml−1 in two subjects, respectively. After two tablets, plateau level maxima around 18 ng ml−1 and 9 ng ml−1 were found, respectively.

After inhalation of a metered aerosol (two puffs of 500 μg each) the drug appeared in plasma within minutes, albeit at very low levels, and usually remained detectable at the sub‐nanogram level during the time of the experiment (2 h).

Due to the very low levels and to some oscillations in the plasma concentration‐time curves, a detailed pharmacokinetic assessment could not be carried out. Effects on heart rate and blood pressure were negligible. Only during the infusion of high doses (540 μg) was there an increase in heart rate of about 50 to 120 beats min−1. Other side‐effects were also negligible.
Pharmacokinetic analyses with rugfit an interactive pharmacokinetic computer program
Authors: Scaf Arnold H. J.
Published: October 2006

RUGFIT is an interactive computer program to fit polyexponential equations to experimental points without the need of assumptions about the number of exponential terms and without the need of initial parameter estimates. The fitting is performed by iterative stripping minimizing the sum of squared residuals. This procedure leads to multiple model equations describing the profile of they‐value in time, that are compared with the test of Boxenbaumet al.

The examples analysed in this paper are: a plasma decay curve after an intravenous bolus injection and one after an oral gift, a dA/dtversus time curve with a lag time and a curve possibly reflecting an entero‐hepatic recirculation. The outcomes are, where possible, compared with the outcomes obtained with the computer programs CFT3, NONLIN, and NONLINEAR (SPSS). The latter three programs sometimes run into a local minimum, as the outcomes obtained with RUGFIT were close to the best ones obtained with the other programs.

The analyses with RUGFIT show that a choice of an inadequate model equation can lead to a marked error in the value of the area under the curve that may result in a marked error of, for instance, the bioavailability. The procedures of RUGFIT are illustrated in the Appendix. RUGFIT also contains options to calculate microparameters, to simulate dosage regimes, to calculate exponents and intercepts from rate constants and to analyse time effect relationships.
Steady state relative bioavailability and pharmacokinetics of oral propranolol in black and white North Americans
Authors: Sharoky Melvin , Perkal Mark , Turner Robert , Lesko L. J.
Published: October 2006

The steady state bioavailability and pharmacokinetics of propranolol over two consecutive dosing intervals were investigated in 18 black and 10 white normal volunteers following the administration of 20 mg of a test and reference oral dosage form, respectively, every 6h. There were no differences (p > 0.05) between dosage forms in the mean (n = 28) area under the plasma concentration‐time curve (AUC), maximum plasma concentration (Gmax) or time to Gmax (tmax) for propranolol or its active metabolite, 4‐hydroxypropranolol. However, as a group blacks had lower plasma concentrations of propranolol and 4‐hydroxypropranolol than whites. The mean AUC and Cmax for propranolol during the second dosing interval (AUC‐2 and Cmax‐2, respectively) were significantly (p < 0.05) lower in blacks, but there were no ethnic differences (p > 0.05) in tmax. The mean AUC and Cmax for the 4‐hydroxylated metabolite during both dosing intervals were significantly (p < 0.05) lower in blacks. Mean oral clearances of propranolol, assuming complete absorption, (range: 42.1–54.5 ml min−1 kg−1) were similar (p > 0.05) in each racial group. There were no substantial changes in heart rate or blood pressure in blacks or whites following propranolol administration. These data suggest that for oral propranolol, blacks have different absorption and disposition characteristics than whites.
Relative bioavailability of a controlled‐release albuterol formulation for twice‐daily use
Authors: Sykes R. S. , Reese M. E. , Chubb J. M. , Meyer M. C.
Published: October 2006

A two‐way‐crossover bioavailability study was completed with 15 healthy male volunteers to evaluate the relative bioavailability of an orally administered controlled‐release (CR) formulation of albuterol as compared to the immediate‐release (IR) formulation of albuterol. The CR formulation of albuterol used in this study was based mechanistically on the elementary osmotic pump.1 Each subject received one 8 mg CR tablet every 12 h for 8 consecutive days and one 4 mg IR tablet every 6 h for 8 consecutive days, with 7 days separating each phase. During day 8 of dosing, hourly blood samples (0–12 h) were collected after the morning dose and three additional samples were obtained 16, 20 and 24 h following this dose. Plasma concentrations were measured using a gas chromatography‐mass spectrometry procedure. No statistically significant differences were observed in mean steady‐state values for Cmax AUC(0–12 h) and peak‐to‐trough fluctuations (PTF) in comparing the two dosage formulations. Mean steady state Tmax values were 2.6 and 6.0 h for the TR and CR formulations, respectively.

It was concluded that twice daily administration of the controlled‐release formulation of albuterol provides an alternative to four times daily administration of conventional (immediate‐release) albuterol tablets.
Drug distribution in dog brain studied by positron emission tomography
Authors: Agon Philippe , Braeckman Rene , Van Haver Dirk , Denutte Hugo , Goethals Patrick , Donche Hendrick , Vermeullen Franklin , Deman Joris , Kaufman Jean‐Marc
Published: October 2006

We used positron emission tomography to monitor the distribution of radioactivity in dog brain and muscle following i.v. administration of 11C‐labelled antipyrine, imipramine, and quinidine.

Twenty‐five sequential scans of a transaxial slice of the head were performed within 90 min; radioactivity in plasma was measured in a gamma‐counter. Following i.v. injection of [11C] antipyrine (50 mg kg−1; 9–68 mCi; n=10), the decay of plasma activity was accompanied by rapid uptake in brain and variable uptake in muscle, immediately followed by a redistribution leading to equalization of the radioactivity in the tissues. Administration of [11C]imipramine (4 mg kg−1; 30–110 mCi; n=8) was followed by a rapid build‐up of a sustained gradient between high brain, and low plasma and muscle radioactivity. After i.v. injection of [11C]quinidine (1 mg kg−1; 11–87 mCi; n=10), radioactivity in brain was low, with higher activity in plasma and muscle throughout the experiment.

Positron emission tomography thus revealed for each drug a distinct pattern of distribution consistent with established properties of the compounds. This technique seems promising for the study of early drug distribution, notwithstanding certain limitations.
Comparison of mRNA abundance quantified by gene expression profiling and percentage of positive cells using immunophenotyping for diagnostic antigens in acute and chronic leukemias
Authors: Kern Wolfgang , Kohlmann Alexander , Schoch Claudia , Schnittger Susanne , Haferlach Torsten
Published: October 2006

BACKGROUND.

Microarray analysis is considered a future diagnostic tool in leukemias. Whereas data accumulate on specific gene expression patterns in biologically defined leukemia entities, data on the correlation between flow cytometrically determined protein expression, which are essential in the diagnostic setting today, and microarray results are limited.

METHODS.

The results obtained by microarray analysis were compared using the Affymetrix GeneChip HG‐U133 system in parallel with flow cytometric findings of 36 relevant targets in 814 patients with newly diagnosed acute and chronic leukemias as well as in normal bone marrow samples.

RESULTS.

In a total of 21,581 individual comparisons between signal intensities obtained by microarray analysis and percentages of positive cell as determined by flow cytometry, coefficients of correlation in the range of 0.171 to 0.807 were obtained. In particular, the degree of correlation was high in the following genes critical in the diagnostic setting: CD4, CD8, CD13 (ANPEP), CD33, CD23 (FCER2), CD64 (FCGR1A), CD117 (KIT), CD34, MPO, CD20 (MS4A1), CD7 (range of r, 0.589–0.807).

CONCLUSIONS.

The present data prove the high degree of correlation between findings obtained by microarray analysis and flow cytometry. They are in favor of a future application of the microarray technology as a robust diagnostic tool in leukemias. Cancer 2006. © 2006 American Cancer Society.
Silencing the receptor EphA2 suppresses the growth and haptotaxis of malignant mesothelioma cells
Authors: Nasreen Najmunnisa , Mohammed Kamal A. , Antony Veena B.
Published: October 2006

BACKGROUND.

The over‐expression of the ephrin‐A1 ligand receptor EphA2 is associated with the growth and metastatic potential of tumors. Although EphA2 is expressed in a variety of tumors, its expression and function in malignant mesothelioma (MM) remain unknown. The authors hypothesized that expression of the receptor EphA2 in MM cells (MMCs) plays a key role in the growth and haptotactic migration of MM. They also hypothesized that silencing EphA2 expression by using small‐interfering RNA (siRNA) inhibits the proliferation and haptotaxis of MMCs and induces apoptosis in MMCs.

METHODS.

The expression of EphA2 in MMCs and in normal pleural mesothelial cells (PMCs) was studied by using real‐time quantitative polymerase chain reaction analysis and Western blot analysis. The growth of MMCs was determined with the WST‐1 cell‐proliferation assay. The haptotactic migration of MMCs and PMCs was determined with a Boyden chamber assay. Expression of caspases was determined with calorimetric assays.

RESULTS.

The results demonstrated that silencing the receptor EphA2 by siRNA significantly reduced the proliferation and haptotactic migration of MMCs compared with controls. Over‐expression of EphA2 with plasmid pcDNA/EphA2 enhanced the proliferation and haptotaxis of MMCs significantly. Knocking down EphA2 expression initiated caspase‐9–mediated apoptosis in MMCs.

CONCLUSIONS.

The current results suggested that constitutive expression of EphA2 may contribute to the aggressive behavior and cellular survival of MMCs. EphA2 may be an effective therapeutic target in patients with mesothelioma. Silencing the receptor EphA2 gene is a novel approach for the containment of growth and migration of tumor in patients with malignant mesothelioma. Cancer 2006. © 2006 American Cancer Society.
NFAT transcription factors in control of peripheral T cell tolerance
Authors: Serfling Edgar , Klein‐Hessling Stefan , Palmetshofer Alois , Bopp Tobias , Stassen Michael , Schmitt Edgar
Published: October 2006

The Ca++‐regulated calcineurin/NFAT cascade is one of the crucial signalling pathways that controls adaptive immunity. However, a number of novel experimental data suggest that, in addition to their role in T cell activation, NFATc transcription factors play also a decisive role in the generation of peripheral tolerance against self‐antigens. This function of NFATc factors is mediated by controlling activation‐induced cell death and clonal anergy of T helper cells and the activity of regulatory T cells. The multi‐functional role of NFATc proteins characterize these transcription factors as key regulators of immunological tolerance and, if dysregulated, of development of autoimmune diseases.
An empirical analysis of US and Japanese health insurance using age–period–cohort decomposition
Authors: Fukuda Kosei
Published: October 2006

Aggregate data on household health insurance expenditure in the US and Japan that are classified by period and age are decomposed into age, period, and cohort effects by using the Bayesian cohort models. These models are developed to overcome the identification problem involved in cohort analysis. Despite the differences between the health insurance systems of the two countries, three interesting empirical findings are obtained. First, in both the countries, the age effects are the most influential, and the cohort effects have negligible influence. The latter provides a striking policy implication since the generational imbalance in social security expenditures is widely recognized in developed countries. Second, in both the countries, the period effects show a roughly upward trend. Finally, the age effects exhibit a roughly upward movement for all age groups in the US; however, in Japan, these effects show a downward movement for the 55–59 age group due to the changes in the health insurance system on retirement. Copyright © 2006 John Wiley & Sons, Ltd.
Combined two‐generation reproduction‐teratogenesis study of zearalenone in the rat
Authors: Becci Peter J. , Johnson William D. , Hess Frederick G. , Gallo Michael A. , Parent Richard A. , Taylor Jean M.
Published: October 2006

The toxicity of zearalenone was studied in two generations of Wistar rats over approximately 10 months. Zearalenone was administered in the diet; the dose levels used were 0, 0.1, 1.0 and 10.0 mg per kg body weight per day in all generations. Animals in the F0 generation were bred twice to produce F1A and F1B generations. The F1A generation was bred to produce the F2A generation. The only lesion found at necropsy that could be attributed to zearalenone administration was increased medullary trabeculation of the femur in animals given the high dose. A dose‐related increase in absolute and relative thyroid, pituitary and adrenal gland weights occurred in male and female rats of both the F1 and F1A generation. The alteration in the weights of these endocrine organs is probably a result of the estrogenic activity of zearalenone. Feeding of zearalenone caused decreases in fertility, number of viable offspring per litter and numbers of corpora lutea, implantations and resorptions per dam. Statistically significant differences were noted in the incidences of a number of skeletal and soft tissue abnormalities in both the F1B and F2A1 fetuses, especially at doses of 1.0 and 10.0 mg kg−1. These lesions most likely indicate a delay in fetal development. Unequivocal teratogenic effects could not be defined.
Comparative toxicity of dietary T‐2 toxin in rats and mice
Authors: Hayes M. A. , Schiefer H. B.
Published: October 2006

The subacute toxic effects of dietary T‐2 toxin were compared in young male Wistar rats, young male Swiss mice and juvenile Swiss mice. Purified T‐2 toxin was fed in the diet at levels of 10 or 20 ppm for 2 or 4 weeks. Dose‐related depressions in food consumption and weight gain consistently occurred in all animals fed T‐2 toxin. Hyperkeratosis of the squamous gastric mucosa, atrophy of the thymus and thymusdependent lymphoid tissues, and lymphopenia occurred in all animals exposed to T‐2 toxin. These effects were most severe in juvenile mice, and least severe in rats. In addition, juvenile mice fed the 20‐ppm level developed erythroid hypoplasia and became severely anemic by 4 weeks. These results demonstrate that dietary T‐2 toxin at levels up to 20 ppm cause similar effects attributable to food refusal and alimentary irritation in both species. However, mice and rats were relatively resistant to hematopoietic suppression. Only the juvenile mice fed 20 ppm developed this potentially lethal toxic effect.
Urinary excretion of 5‐hydroxyindolacetic acid in occupational exposure to polyvinyl chloride and polyurethane foams
Authors: Korićanac Z. , Stanković B. , Milovanović J. L. , Dugandžić M. , Trpković D.
Published: October 2006

The effect of plastics as polyurethane foams and polyvinyl chloride on the metabolism of tryptophan was investigated by determining the concentration of 5‐hydroxyindolacetic acid (5‐HIAA) as its metabolic end product excreted in the urine. Investigation of persons occupationally exposed to polyurethane and polyvinyl chloride showed that these plastics inhibit the metabolism of tryptophan, causing increased excretion of its easily measurable metabolite 5‐HIAA. This fact points to the possibility of practical use of this laboratory test which, together with other biological parameters, could improve methods for early detection of occupational exposure to polyurethanes and polyvinyl chloride.
Iodine in diet increases mercury absorption in rats
Authors: Kostial Krista , Kargačin Biserka , čimonović Ivan
Published: October 2006

Increasing the iodine content of rats diets caused an increase in the whole‐body retention of 203Hg after oral, but not after intraperitoneal, administration. That iodine increases gastrointestinal absorption of inorganic mercury might be of interest in conditions of simultaneous environmental exposure to both elements, and therefore deserves further investigations.
Evaluation of the skin uptake of mercuric chloride in man
Authors: Baranowska‐dutkiewicz Bożena
Published: October 2006

Skin on the forearms of male human volunteers was exposed to aqueous HgCl2 solutions. It was assumed that loss of mercury from the test solution was equivalent to percutaneous absorption. Two parameters important for influencing uptake considered as the rate of absorption were investigated: the concentration of HgCl2 solutions (0.01, 0.1 and 0.2 M) and the time of exposure (5, 10, 15, 30 and 60 min). The absorption rate from 0.1 M HgCl2 solution decreased from 9.3 μg cm−2 min−1 during a 5 min exposure to 2.5 μg cm−2 min−1 during a 1 h exposure. A ten‐fold decrease of HgCl2 concentration resulted in an approximately ten‐fold decrease of the absorption rate, from 4.6 to 0.4 μg cm−2 min−1 during a 30 min exposure. The results indicate that the absorption rate is a directly related function of concentration and an indirectly related function of time of exposure.
Inhibition of mixed‐function oxidase activities in vitro and in vivo: Comparisons between kidney and liver
Authors: Kluwe W. M. , Herrmann‐kluwe C. L. , Hook J. B.
Published: October 2006

The concentration‐dependent abilities of SKF 525‐A, metyrapone (MET), piperonyl butoxide (PB), allyl‐isopropylacetamide (AIA) and α‐napthoflavone (7.8‐benzoflavone; ANF) to inhibit the activities of p‐chloro‐N‐methylaniline‐N‐demethylase (PCNMA) and aryl hydrocarbon hydroxylase (AHH) in vitro were determined in microsomal and postmitochondrial supernatant (PMS) fractions of homogenates prepared from kidneys and livers of rats and mice. Renal microsomal AHH was less sensitive to modulation by SKF 525‐A, MET and ANF in vitro than was hepatic microsomal AHH, but renal and hepatic microsomal AHH were equisensitive to inhibition by PB. AIA did not inhibit AHH activities in vitro. Renal AHH and PCNMA activities in PMS fractions were less sensitive to inhibition by SKF 525‐A, MET and PB than were hepatic AHH and PCNMA activities. The temporal characteristics of enzyme inhibition in vivo were studied in kidneys and livers removed 1, 2, 4 or 12 h after treatment of the animals with 75 mg kg−1 SKF 525‐A or 600 mg kg−1 PB. The degree of inhibition of AHH and PCNMA activities produced by i.p. administration of the inhibitors were greater quantitatively in liver PMS than in kidney PMS, and the degree of inhibition of PCNMA activity in both organs was much less than that of AHH activitiy. The differences in sensitivity of renal and hepatic AHH and PCNMA activities to the inhibitors may have been due to organ‐specific differences in the affinities of the inhibitors for interaction with the active site(s) on cytochrome P‐450.
MS/MS analysis of diesel emissions and fuels treated with NO2
Authors: Henderson Thomas R. , Royer Robert E. , Clark Charles R. , Harvey T. M. , Hunt D. F.
Published: October 2006

Correlations between direct‐acting mutagens in diesel emissions and the activity of nitroaromatic compounds have been noted, but detection and identification of nitro‐compounds in diesel particulates has remained an elusive problem. In the results reported here, MS/MS (tandem mass spectrometry) was found to detect nitroaromatic compounds in fractionated and unfractionated diesel soot extracts. The nitro‐compounds detected ranged from two‐ to four‐ring polynuclear aromatic hydrocarbon derivatives and were primarily mono‐nitroderivatives. An aromatic fraction from diesel fuel reacted with NO2 resembled diesel exhaust extracts from an engine operating on the same fuel. Therefore, it is possible that nitroaromatic derivatives in diesel exhaust may be in part due to unburned fuel residues reacting with NOx formed in the combustion process. The utility of MS/MS in comparing complex mixtures from different sources or subfractions thereof is discussed.
Isotoxic oral and inhalation exposure of carbon tetrachloride in Porton–Wistar and Fischer rats
Authors: Magos L. , Snowden R. , White I. N. H. , Butler W. H. , Tuffery A. A.
Published: October 2006

Male Fischer or Porton–Wistar rats were exposed for 4 h to different atmospheric concentrations of CCl4 or were given increasing oral doses of CCl4 in order to estimate isotoxic exposures or doses. Animals were killed 20 h after treatment, their serum glutamic–pyruvic transaminase activities were measured and their livers were processed for histological examination. It has been found that the equitoxic oral dose in Wistars is 1.5 times that in Fischer rats and more than 3 times after inhalation. Therefore, the conversion factors from inhalation exposure to oral dose were much higher for Fischer than for Porton–Wistar rats. After oral dosing, the extent of centrilobular damage in Fischer rats was approximately twice that in Porton–Wistar rats. After inhalation exposure, the extent of damage was the same in the two strains, but at least at the two lower exposure levels hydropic degeneration definitely contributed to the size of the damaged areas more in Porton‐Wistar than in Fischer rats.
Long‐term carcinogenicity and toxicity study of zearalenone in the rat
Authors: Becci Peter J. , Voss Kenneth A. , Hess Frederick G. , Gallo Michael A. , Parent Richard A. , Stevens Kent R. , Taylor Jean M.
Published: October 2006

The effects of lifetime dietary administration of zearalenone, a fungal estrogen produced by Fusarium spp., were studied in FDRL Wistar rats. Animals were fed a control diet or a diet supplemented with zearalenone at levels of 0.1, 1.0 or 3.0 mg per kg body weight per day. The animals used were derived from F0 parents fed equivalent levels of zearalenone for 5 weeks before mating, and throughout mating and gestation, but not during lactation. Feeding of zearalenone at 1.0 and 3.0 mg kg−1 to male rats caused a significant decrease in body weight gain compared with controls. During the study, sporadic depressions in body weights occurred in females fed 1.0 and 3.0 mg per kg. However, no differences were noted at the end of the study. No significant differences among groups were found in the hematology, clinical chemistry or urine analysis data measured during or at the termination of the study. At the end of the study, significantly increased liver weights at the 3.0 mg kg−1 dose level and uterine weights at 1.0 and 3.0 mg kg−1 were noted in female rats. These weight differences did not correlate with any clinical or morphological finding. In rats receiving the high dose level of zearalenone, a greater incidence of increased medullary trabeculation of the femur was noted. The degree of medullary trabeculation was scored on a scale from 0 to 4; statistically significant increased scores were found in male and female rats at the high dose level compared to control rats. Other microscopic findings were unremarkable; no tumorigenic effect of zearalenone was noted.
Teratogenicity following inhalation exposure of rats to a high‐boiling coal liquid
Authors: Springer D. L. , Poston K. A. , Mahlum D. D. , Sikov M. R.
Published: October 2006

On days 12–16 of gestation pregnant rats were exposed to heavy distillate (HD), the highest‐boiling material derived from the solvent refined coal‐II (SRC‐II) process, and the litters were examined at day 21. Adverse biological effects were observed in the group of animals exposed to an aerosol concentration of 0.66 mg l−1 [1.8 μm, mass medium aerodynamic diameter (MMAD)]; groups of animals exposed to lower aerosol concentrations (0.084 and 0.017 mg l−1) were largely unaffected. Embryolethality during mid‐ and late gestation appeared attributable to the coal liquid exposure. Fetuses from pregnant rats in the high exposure group were smaller in weight and length than fetuses from control animals, and skeletal ossification was reduced. Increased incidences of small lungs and cleft palate were observed in fetuses from the high exposure group. Pregnant rats in the high‐exposure group gained less weight than controls during gestation; the reduced weight gain was accounted for by the reduced size of the fetuses and placentas. Even though maternal body weight (exclusive of the products of conception) was unaffected by the exposure, the weights of the maternal thymus, lung and spleen were altered in the high exposure group.
Short‐term toxicological studies with impromidine (SK&F 92676): A specific histamine H2‐receptor agonist
Authors: Leslie G. B. , Owen D. A. A. , Pollitt Frances D. , Sutton T. J. , Walker T. F.
Published: October 2006

Impromidine is a specific, potent histamine H2‐receptor agonist. The present paper describes the results of acute and short‐term repeated‐dose toxicity studies with impromidine in rodents and dogs. The intravenous LD50 was 9.6 mg kg−1 in male mice, 12.7 mg kg−1 in female mice and 25.5 mg kg−1 in rats. The minimum lethal dose in dogs after 30 min intravenous infusion was 27.7 mg kg−1 during the infusion and 4 mg kg−1 within 14 days. In 12‐ or 14‐day tests in rats by the intravenous (maximum dose 3.24 mg per kg per day) and subcutaneous (maximum dose 20 mg per kg per day) routes, impromidine had no serious toxicological effects. In 12‐ or 14‐day studies in dogs by the i.v. (maximum dose 0.259 mg per kg per day) and intramuscular (maximum dose 0.5 mg per kg per day) routes, impromidine caused vasodilation, tachycardia and vomiting. In a few dogs, at the highest dose levels, there was erosion and irritation of the gastrointestinal tract and myocardial damage. Other minor pathological changes were seen in the liver, kidneys and pancreas. No changes were seen other than those to be expected from the pharmacological actions of impromidine as an H2‐receptor agonist. Studies in anaesthetized rats, either spontaneously respiring or sustained by artificial respiration, indicate that, at acute doses, impromidine causes death by respiratory failure.
Co‐enzyme effects of inorganic mercury in the liver of a freshwater fish Channa punctatus
Authors: Rana S. V. S. , Sharma Rekha
Published: October 2006

Mercury is known to modify enzyme activity through oxidation of thiol groups and respective reverse reactions in vitro and in vivo. However, variations in the activity of carbohydrases, and the significance of this variation after mercury poisoning in different species, has not been established. In the present report, the effects of inorganic mercury on selected hepatic enzymes was studied in the freshwater fish Channa punctatus. Quantitative data clearly showed a dose–response relationship between the amount of mercury retained in the liver and inhibition of enzymes (i.e. alkaline phosphatase, glucose‐6‐phosphatase, amylase, maltase, lactase, lipase and dehydrogenases). Mechanisms and significance of their modification have also been discussed.
Comparative effects of structurally related cyclodiene pesticides on ATPases
Authors: Mehrotra B. D. , Bansal S. K. , Desaiah D.
Published: October 2006

Comparative effects of aldrin, dieldrin, endrin, isodrin and telodrin, on different ATPase activities in beef heart mitochondrial and rat brain synaptosomal fractions were determined in vitro. Beef heart mitochondrial fractions were prepared by the conventional centrifugation method and the rat brain synaptosomes were prepared by Ficoll‐sucrose gradient centrifugation method. Na+–K+‐ATPase, oligomycin‐sensitive and ‐insensitive Mg2+‐ATPases, and K+‐paranitrophenylphosphatase were determined in rat brain synaptosomes. In beef heart mitochondria, only the Mg2+‐ATPase activities were determined. Concentration response curves were determined by assaying the enzyme activities in the absence and presence of 10–120 μM concentrations of each test chemical. Beef heart mitochondrial (oligomycin‐sensitive) Mg2+‐ATPase activity was inhibited by all five chemicals at all the concentrations tested. Aldrin and telodrin were the most potent inhibitors with an IC50 of 40 and 80 μM, respectively. About 30% was observed with dieldrin, endrin and isodrin, and the inhibition was not concentration‐dependent. Oligomycin‐insensitive Mg2+‐ATPase was not significantly inhibited by any chemical except aldrin. Rat brain synaptosomal ATPases were also sensitive to these compounds. Aldrin and telodrin were more effective than other compounds. A 50% inhibition of oligomycin‐sensitive Mg2+‐ATPase activity was obtained at 80 μM of aldrin and telodrin, Na+–K+‐ATPase and oligomycin‐insensitive Mg2+‐ATPase activities showed a maximum inhibition of 40% at the highest concentration tested for aldrin and telodrin. K+‐paranitrophenylphosphatase was not inhibited significantly by any compound tested. These results suggest that ATPase system in rat heart and CNS may be selectively inhibited by aldrin and telodrin, but not by their structural analogs.
Fluoride absorption through the hamster cheek pouch: A pH‐dependent event
Authors: Whitford G. M. , Callan R. S. , Wang H. S.
Published: October 2006

The fractional absorptions of fluoride, 3H2O, 125I and 14C‐DMO from the hamster cheek pouch were determined as functions of solution pH. When the pH was ≥5, fluoride absorption rate was inversely related to pH. The absorption rates of the other substances were not influenced by pH. The fractional absorptions of fluoride and 3H2O were independent of fluoride concentrations over the range 1–53 mM. The data indicate that the absorption of fluoride through this keratinized epithelium occurs mainly by the diffusion of non‐ionic HF.