РАЗЛИЧИЕ РАКА ТОЛСТОЙ И ПРЯМОЙ КИШКИ С ТОЧКИ ЗРЕНИЯ ЭПИДЕМИОЛОГИИ, КАНЦЕРОГЕНЕЗА, МОЛЕКУЛЯРНОЙ БИОЛОГИИ, ПЕРВИЧНОЙ И ВТОРИЧНОЙ ПРОФИЛАКТИКИ: ДОКЛИНИЧЕСКИЕ ИССЛЕДОВАНИЯ

Introduction. Colon and rectal cancer (CC, RC) are different entities from a clinical and tumor biological point of view. Up to now, both, CC and RC, are synonymously called  “Colorectal Cancer” (CRC). With our experience in basic and clinical research and routine  work in this field we now have come to the opinion, that the term “CRC” should definitely be questioned, and if justified, be abandoned.Materials/Methods. We analyzed the actual available data from the literature and our own  results from the Ulm based study group FOGT to proof or reject our hypothesis.Results. The following evident differences were recognized: Anatomically, the risk to  develop RC is 4× higher than for CC. Molecular changes in carcinogenesis in CC are different from RC. Physical activity helps to prevent CC, not RC. Pathologically there are differences between RC and CC. In addition, there are also major clinical differences  between CC and RC, such as in surgical topography and– procedures, multimodal treatment  (MMT) approaches (RC in MMT is less sensitive to chemotherapy than CC), and prognostic  factors for the spontaneous course and for success of MMT (e.g. TS or DPD ). Discussion. CC ´sand RC´s definitely are different in parameters of causal and formal carcinogenesis, effectivity of primary prevention by physical activity, conventional and  molecular pathology.According to our findings we can demand from the preclinical point of  view that CC and RC are two different tumor entities in terms of various representative  biological characteristics.CC and RC are also differing substantially in many clinical features, as outlined in a separate paper from our group.Conclusion. “CRC” should no longer be used in basic and clinical research and other fields  of cancer classification as a single disease entity. CC is not the same as RC. CC might even be divided into right and left CC.Введение. Рак толстой и прямой кишки – разные опухоли с клинической и биологической точек зрения. В  настоящее время рак толстой и прямой кишки синонимично называют колоректальным раком. Основываясь  на нашем опыте в фундаментальных и клинических исследованиях в этой области, мы пришли к выводу, что  термин «колоректальный рак» необходимо пересмотреть, его нельзя использовать как обобщающее понятие.Материал и методы. Были проанализировали данные литературы и собственные результаты исследований, чтобы доказать или отклонить эту гипотезу.Результаты. Выявлены следующие очевидные различия: риск развития рака прямой кишки в 4 раза выше,  чем рака толстой кишки; молекулярный канцерогенез при раке толстой кишки отличается от рака прямой  кишки; физическая активность помогает предотвратить рак толстой кишки, но не прямой кишки;  существуют патогистологические различия между раком прямой и толстой кишки. Кроме того, имеются  значительные клинические отличия между этими злокачественными новообразованиями, такие как  различная хирургическая топография и объемы операций, разные показания для назначения  комбинированного лечения, поскольку рак прямой кишки менее чувствителен к химиотерапии, чем рак  толстой кишки, и отличаются прогностические факторы эффективности мультимодальной терапии  (например, тимидилат синтетаза и дигидропиримидин дегидрогеназа).Дискуссия. Рак толстой и прямой кишки определенно различаются по этиологии и формальному  канцерогенезу, эффективности первичной профилактики, связанной с физической активностью, обычной и  по параметрам молекулярной патологии. Согласно нашим данным, можно утверждать, что с доклинической  точки зрения рак толстой и прямой кишки являются двумя разными опухолями, поскольку обладают  различными репрезентативными биологическими характеристиками. Рак толстой и прямой кишки также  существенно различаются по многим клиническим признакам, что было указано в отдельной статье,  представленной нашей исследовательской группой. Заключение. Термин «колоректальный рак» не должен  использоваться в фундаментальных и клинических исследованиях, как определение единого заболевания.  Рак толстой кишки не одно и то же, что и рак прямой кишки. Злокачественные новообразования толстой  кишки могут быть разделены на рак правой и левой половины ободочной кишки

Oxytocin at physiological concentrations evokes adrenocorticotropin (ACTH) release from corticotrophs by increasing intracellular free calcium mobilized mainly from intracellular stores. Oxytocin displays synergistic or additive effects on ACTH-releasing factor or arginine vasopressin-induced ACTH secretion, respectively

The potency of oxytocin (OT) in evoking ACTH secretion by isolated, superfused rat adenohypophyseal corticotrophs and its enhancement by CRF and arginine vasopressin (AVP) were analyzed. Each secretagogue effectively released ACTH from adenohypophyseal cells when added separately in pulsatile fashion in physiological concentrations based on hypophyseal portal blood (OT, 10 nM; AVP, 0.5 nM; CRF, 0.1 nM). OT released ACTH at concentrations as low as 1 nM. Moreover, a dose- response relationship up to 10 microM was revealed. Combinations of a constant amount of CRF (0.1 nM) with increasing concentrations of OT exerted a synergistic effect on ACTH release. In contrast, OT given in various concentrations in combination with AVP (0.5 nM) produced an additive effect on ACTH release. To study the mechanism of action of OT on ACTH secretion, cytosolic free calcium levels in single pituitary cells exposed to OT or AVP were measured using the calcium-sensitive fluorescent indicator Fura-2. Corticotrophs among mixed adenohypophyseal cell types in the primary cultures were identified by immunocytochemistry. More than 500 cells were individually stimulated with OT or AVP. Basal cytosolic free calcium levels ranged between 80- 130 nM free calcium. The addition of 100 nM OT or 1 microM AVP increased the cytosolic free calcium concentration within 3 sec to values ranging from 500-800 nM. An increase in intracellular calcium ranging from 200-500 nM due to OT could still be observed after extracellular calcium depletion. Taken together, our data demonstrate that physiological concentrations of OT stimulate ACTH secretion, independent of the other ACTH secretagogues, by mobilizing calcium mainly from intracellular stores

Effect of oxytocin on free intracellular Ca2+ levels and progesterone release by human granulosa-lutein cells

Oxytocin and its receptor are found in the corpus luteum in a variety of species, including the human. In the present study we used fura-2 microfluorimetry to investigate whether activation of the oxytocin receptor of cultured human granulosa-lutein cells causes intracellular calcium (Ca2+) signals and affects progesterone release. Although after 1 day in culture, cells were not responsive to oxytocin, the number of responsive cells increased steadily during the first 3 days in culture, reaching a maximum on days 4 and 5 (59-66%) and then declined again until day 8. Effective oxytocin concentrations were apparently independent of the culture day, and concentrations as low as 10 nmol/L increased intracellular free Ca2+ levels from 70-140 nmol/L (basal levels) to maximal peak levels of 800 nmol/L. The oxytocin-induced Ca2+ signal was not affected by removal of extracellular Ca2+ with EGTA. Moreover, depletion of intracellular Ca2+ stores by ionomycin treatment rendered the cells unresponsive to oxytocin, pointing also at the intracellular source of the oxytocin-inducible Ca2+ signal. Interestingly, after one single stimulation with oxytocin, cells became refractory to additional stimuli, and only extremely high concentrations of oxytocin induced a second increase in intracellular free Ca2+. To examine the possible effects of oxytocin on progesterone release by cultured cells, we incubated cells on culture day 2 (20% responsive cells in the fura measurements) and culture day 5 (66% responsive cells in the fura measurements) for 24 h with oxytocin (10 nmol/L) and hCG (10,000 IU/L). Although hCG significantly stimulated progesterone release, oxytocin alone was without a stimulatory effect on either day. However, a significant augmentation of the effect of hCG on progesterone release was found in incubations of cells on day 5. Interestingly, the effects of hCG also included stimulation of oxytocin release by cultured granulosa-lutein cells into the culture medium, as determined by RIA. In summary, our data indicate the presence of a functional oxytocin receptor on human granulosa-lutein cells that is linked to Ca2+ as a second messenger released from intracellular Ca2+ stores. The number of oxytocin-responsive cells increases during differentiation in culture. Moreover, oxytocin release induced by hCG and a stimulatory effect of oxytocin on the hCG-induced progesterone production during the period of maximal responsiveness of cultured cells were found. We, therefore, propose that oxytocin may have autocrine and/or paracrine functions in human granulosa-lutein cells, including fine-tuning of progesterone release

Intercalation of graphene on SiC(0001) via ion-implantation

Electronic devices based on graphene technology are catching on rapidly and the ability to engineer graphene properties at the nanoscale is becoming, more than ever, indispensable. Here, we present a new procedure of graphene functionalization on SiC(0001) that paves the way towards the fabrication of complex graphene electronic chips. The procedure resides on the well-known ion-implantation technique. The efficiency of the working principle is demonstrated by the intercalation of the epitaxial graphene layer on SiC(0001) with Bi atoms, which was not possible following standard procedures. Our results put forward the ion-beam lithography to nanostructure and functionalize desired graphene chips

Long-Distance Contributions to D^0-D^0bar Mixing Parameters

Long-distance contributions to the $D^0$-$\bar D^0$ mixing parameters $x$ and $y$ are evaluated using latest data on hadronic $D^0$ decays. In particular, we take on two-body $D \to PP$ and $VP$ decays to evaluate the contributions of two-body intermediate states because they account for $\sim 50$ of hadronic $D^0$ decays. Use of the diagrammatic approach has been made to estimate yet-observed decay modes. We find that $y$ is of order a few $\times 10^{-3}$ and $x$ of order $10^{-3}$ from hadronic $PP$ and $VP$ modes. These are in good agreement with the latest direct measurement of $D^0$-$\bar D^0$ mixing parameters using the $D^0 \to K_S \pi^+\pi^-$ and $K_S K^+ K^-$ decays by BaBar. We estimate the contribution to $y$ from the $VV$ modes using the factorization model and comment on the single-particle resonance effects and contributions from other two-body modes involving even-parity states.Comment: 18 pages and 1 figure; footnotes and references added; to appear in Phys. Rev.

Rising Level of Public Exposure to Mobile Phones: Accumulation through Additivity and Reflectivity

A dramatic development occurring in our daily life is the increasing use of mobile equipment including mobile phones and wireless access to the Internet. They enable us to access several types of information more easily than in the past. Simultaneously, the density of mobile users is rapidly increasing. When hundreds of mobile phones emit radiation, their total power is found to be comparable to that of a microwave oven or a satellite broadcasting station. Thus, the question arises: what is the public exposure level in an area with many sources of electromagnetic wave emission? We show that this level can reach the reference level for general public exposure (ICNIRP Guideline) in daily life. This is caused by the fundamental properties of electromagnetic field, namely, reflection and additivity. The level of exposure is found to be much higher than that estimated by the conventional framework of analysis that assumes that the level rapidly decreases with the inverse square distance between the source and the affected person. A simple formula for the exposure level is derived by applying energetics to the electromagnetic field. The formula reveals a potential risk of intensive exposure.Comment: 5 pages, 1 fugure; to appear in J. Phys. Soc. Jpn. Vol.71 No.2 in Feb 200

Microscopic theory of quadrupolar ordering in TmTe

We have calculated the crystal electric field of TmTe (T>T_Q) and have obtained that the ground state of a Tm 4f hole is the $\Gamma_7$ doublet in agreement with Mossbauer experiments. We study the quadrupole interactions arising from quantum transitions of 4f holes of Tm. An effective attraction is found at the L point of the Brillouin zone, $\vec{q}_L$. Assuming that the quadrupolar condensation involves a single arm of $\vec{q}_L$ we show that there are two variants for quadrupole ordering which are described by the space groups C2/c and C2/m. The Landau free energy is derived in mean-field theory. The phase transition is of second order. The corresponding quadrupole order parameters are combinations of $T_{2g}$ and $E_g$ components. The obtained domain structure is in agreement with observations from neutron diffraction studies for TmTe. Calculated lattice distortions are found to be different for the two variants of quadrupole ordering. We suggest to measure lattice displacements in order to discriminate between those two structures.Comment: 10 pages, 2 figures, 5 tables; accepted by PR

Antiferroquadrupolar Order in the Magnetic Semiconductor TmTe

The physical properties of the antiferroquadrupolar state occurring in TmTe below TQ=1.8 K have been studied using neutron diffraction in applied magnetic fields. A field-induced antiferromagnetic component k = (1/2,1/2,1/2) is observed and, from its magnitude and direction for different orientations of H, an O(2,2) quadrupole order parameter is inferred. Measurements below TN ~= 0.5 K reveal that the magnetic structure is canted, in agreement with theoretical predictions for in-plane antiferromagnetism. Complex domain repopulation effects occur when the field is increased in the ordered phases, with discontinuities in the superstructure peak intensities above 4 T.Comment: 6 pages, 6 figures, Presented at the International Conference on Strongly Correlated Electrons with Orbital Degrees of Freedom (ORBITAL 2001), September 11-14, 2001 (Sendai, JAPAN). To appear in: Journal of the Physical Society of Japan (2002

Thermodynamical Study on the Heavy-Fermion Superconductor PrOs4Sb12: Evidence for Field-Induced Phase Transition

We report measurements of low-temperature specific heat on the 4f^2-based heavy-fermion superconductor PrOs4Sb12. In magnetic fields above 4.5 T in the normal state, distinct anomalies are found which demonstrate the existence of a field-induced ordered phase (FIOP). The Pr nuclear specific heat indicates an enhancement of the 4f magnetic moment in the FIOP. Utilizing a Maxwell relation, we conclude that anomalous entropy, which is expected for a single-site quadrupole Kondo model, is not concealed below 0.16 K in zero field. We also discuss two possible interpretations of the Schottky-like anomaly at ~3 K, i.e., a crystalline-field excitation or a hybridization gap formation.Comment: 5 pages with 5 figures, a note with two references added in proo