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Simian-immunodeficiency-virus(SIV)-infected cynomolgus monkeys develop B-cell lymphomas in approximately one third of the cases. We have now studied the expression of cynomolgus-Epstein-Barr-virus(cyno-EBV) nuclear antigens in 13 cyno-EBV-carrying SIVsm-associated monkey lymphomas and established cell lines from 3 of these tumors. Immunoblots of cell lysates were probed with polyspecific and monospecific reagents directed against human EB-virus EBNAI-6, and against the membrane protein LMPI. An EBNA2-cross-reacting protein was demonstrated in 8 lymphoma tissues (8/13) and in the 3 cell lines derived from the tumors. All tumors expressed a polypeptide with 50 to 55 kDa molecular weight, which cross-reacted with some antibodies to EBNAI. Absorption experiments with normal monkey tissue showed that this polypeptide was specific for the cyno-EBV-carrying lymphoma cells. Equivalents of EBNA3-6 and LMPI could not be detected. Immunophenotypical characterization showed that the monkey lymphomas were similar to human HIV-associated B-cell lymphomas. Malignant B-cell lymphomas in experimentally SIVsm-infected cynomolgus monkeys can be a model for EBV-associated lymphomagenesis in immunodeficiency states.

Described here is a family in which the father with partial C4 deficiency had Wegener's granulomatosis and a son with complete C4 deficiency presented with Henoch-Schönlein Purpura. The possible role of C4 deficiency in the pathogenesis of both vasculitic disorders is discussed.

e21076 Background: Mutation of the K-ras oncogene was identified as predictive and potentially prognostic in colorectal and pancreatic cancer. Less is known about the influence of the K-ras status ...

In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.

Purpose To investigate the effect of EGF, IGF-1, and VEGF on ARPE19 cell proliferation and differentiation. Methods The gene expression of RPE-specific differentiation and proliferation markers and the transcriptional and translational activity of beta-catenin signaling markers were measured by flow cytometry and RT-PCR. Results The data showed a significant decrease in RPE65, CRALBP, and cytokeratin 18 in ARPE-19 cells stimulated with EGF and IGF-1. In addition, a significant decrease in GSK-3beta and beta-catenin was observed that was paralleled by an increase in cyclin D1 expression. Cell cycle studies revealed an increase in ARPE cells in the S-G(2)/M-phase after treatment with EGF or IGF-1. VEGF, on the other hand, led to a reduction in cyclin D1 and to an increase in GSK 3beta and beta-catenin expression which was paralleled by an increase in RPE-specific differentiation markers. Conclusions The data demonstrate the induction of proliferation by EGF and IGF-1 and upregulation of the beta-catenin signaling pathway in ARPE-19 cells. The data suggest that activation of the beta-catenin signaling pathway may be key in activating ARPE-19 cells by different growth factors.

Malignant lymphomas were observed in 38% (9 of 24) of simian immunodeficiency virus (SIV)-infected cynomolgus monkeys (Macaca fascicularis) 5 to 15 months after inoculation with SIV strain SMM3. Lymphomagenesis in the SIV-infected monkeys was not related directly to the SIV-infectious dose given. All SIV-infected animals developed severe immunodeficiency. No significant difference in immunodeficiency was observed between tumor-bearing and non-tumor-bearing animals. In contrast, no lymphomas were observed in a comparable group of HIV-2-infected monkeys, which did not develop immunodeficiency; nor did the noninfected control monkeys. All 9 SIV-related tumors were high-grade B-cell lymphoblastic or pleomorphic lymphomas with extranodal, disseminated growth. Most tumors showed marked infiltration by monocytes and CD8+ T lymphocytes. Occasional tumor infiltrating cells showed immunohistochemical reaction for SIV. The cells of two tumors were established in vitro and shown to be of B-cell phenotype. The tumor cell cultures showed no reverse transcriptase activity and no evidence of virus infection by electron microscopy. Our observations indicate that SIV-induced immunodeficiency in cynomolgus monkeys also mimics HIV infection and AIDS in humans with regard to increased lymphomagenesis and type of lymphomas.

Rhodium, which is believed to favour interstitial diffusion in silicon (corresponding to its high diffusivity), forms levels in the upper half of the silicon band gap which are attributed to a substitutional site. Gold in silicon diffuses mainly via its interstitial component, while the formation of substitutional gold is controlled by a kick-out mechanism creating self-interstitials. We observe a strong enhancement of substitutional gold formation in rhodium-doped samples at low diffusion temperatures which can be understood by assuming a AuRh kick-out reaction. The kinetic behaviour is demonstrated by annealing experiments which are observed by means of deep-level transient spectroscopy.

Photocapacitance measurements on n-type iron-doped silicon reveal two deep levels one near the middle of the gap and one at (0.75+or-0.01) eV below the conduction band edge. The electron photoionisation cross-section spectrum for both levels has been measured at liquid nitrogen temperature by a transient photocapacitance technique. There is evidence from EPR measurements reported elsewhere that the lower level is due to the transition Fe0 to Fe+ at interstitial iron. The concentration of both levels decreases on heating at 90 degrees C. The concentration does not decay as a simple exponential function of time but tends towards a constant value for both levels. The initial slope of the decay curve for the interstitial iron level gives a migration energy of (0.66+or-0.01) eV in good agreement with reported values.

Comparaison des resultats experimentaux obtenus par les auteurs avec des resultats theoriques ou experimentaux d'autres auteurs; concernant la modification de la structure de bande entrainee par Fe et Cr en position d'interstitiels dans Si

Interstitial manganese in silicon can exist in four charge states which imply single acceptor and double donor behaviour. The corresponding level scheme with the acceptor level ( Mn − 0 ) at Ec-0.13eV, the first donor level ( Mn 0 + ) at Ec−0.45eV and the second donor level (Mn+/++) at Ev+0.30eV is established through EPR-controlled Hall measurements. Another deep donor level at Ec−0.54eV is produced by the donor acceptor pair (MnB) whereas a more shallow one around Ec-0.28eV was already attributed to a Mn4-cluster.

Carcinoid tumours (bronchial and intestinal) were analyzed by immunoblotting for the presence of chromogranin A, B and secretogranin II. In all tumours an antigen corresponding in electrophoretic behaviour to adrenal chromogranin A was present. Lung carcinoids (3 out of 5) contained a relatively high concentration of a proteoglycan form of this antigen in addition. Chromogranin B was found in all tumours. In one and two dimensional immunoblotting it appeared identical to the corresponding adrenal antigen. Secretogranin II was also present, however concentrations (especially in intestinal carcinoids) were low and variable. Furthermore, in intestinal tumours it differed from the adrenal antigen by having a slightly higher molecular size and a more alkaline pI. Immunohistochemistry revealed that the tumour tissues stained positively for all three antigens. For secretogranin II the staining in intestinal tumours was relatively weak and quite variable. These results should provide a defined basis for immunohistochemical screening of carcinoids for the chromogranin/secretogranin antigens.

We investigated a variety of endocrine tumors for the presence of chromogranins A and B and secretogranin II. These antigens were identified by one- and two-dimensional immunoblotting and in some cases by immunohistochemistry. An antigen corresponding in electrophoretic behavior to adrenal chromogranin A was present in all types of tumors, including insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin. Chromogranin B had a much more limited distribution. This antigen could not be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell tumors, either by immunoblotting and immunohistochemistry. The occurrence of secretogranin II was similar to that of chromogranin B, with the exception of a positive reaction in Merkel cell tumors. In benign pheochromocytomas, all three antigens were found consistently; whereas in two of three malignant pheochromocytomas, chromogranin B was absent. Our study establishes that in most cases chromogranins and secretogranin in tumors are identical to the adrenal antigens, but that these antigens are not always stored together. Chromogranin A is the most widely distributed marker for endocrine tumors.

Silicon samples were quenched from 1250°C – 1300°C and the 95K Fermi level was calculated from Hall effect data. The same samples were used to determine the intensity of the EPR spectrum at 95K associated with the iron interstitial (Fe°). In carefully selected samples, complete or partial overlapping of temperature dependent Hall measurements and EPR spectra could be accomplished. By relating Fermi levels to the corresponding EPR signals it was found that the transition Fe° → Fe+ in silicon introduces a level located at Ev+0, 375eV.

A combination of deep level transient spectroscopy (DLTS) and electron spin resonance (ESR) measurements was used to determine the energy level of substitutional manganese in silicon. Samples of p‐type silicon were subjected to a copper‐manganese codiffusion. Successfully prepared samples show the typical ESR signal of substitutional manganese with a single positive charge. The Hamiltonian parameters g=2.029 and A=−62.7×10−4 cm−1 are different from those for negatively charged interstitial manganese. The DLTS measurements reveal an energy level of M1=0.39 eV above the valence‐band edge for the substitutional manganese. Because of the codiffusion of Cu also the previously reported levels C1=0.098 eV, C2=0.22 eV, and C3=0.41 eV were found. The combination of ESR and DLTS results allowed a conclusive identification of the defect level M1 and provided no evidence for ordinary amphoteric or negative U behavior in the lower half of the band gap. Furthermore, isothermal and isochronal annealing experiments were ...

A versatile method for analysing experimental curves with exponential character is presented. By introducing an exponential x deflection instead of the normally used linear time-base of an oscilloscope the determination of time constants of exponential curves is transferred via manual tuning to the externally generated x deflection. On account of this the time constants can be derived from a signal essentially free of noise and ambiguity and may easily be obtained in digital form. Based on this idea a device has been developed which is described in some detail. As an example of the method's application, trap studies in heated silicon are reported.

Zur Entschwefelung von Gasolen wurde ein Selektivraffinationsverfahren entwickelt. welches mit 98 prozentiger Flussaure als Losungsmittel arbeitet. Die entschwefelnde Wirkung von Flussaure, Schwefelsaure und Kalilauge mit Kaliumisobutyrat-Zusatz gegenuber Gasolen wird verglichen. Die bei 760 Torr bis 320°C siedenden Inhaltsstoffe der untersuchten Mineralolfraktionen konnten mit Flussaure weitgehend entschwefelt werden.

n-type and p-type silicon crystals were quenched from 900 to 1400 °C into a cooling liquid. From Hall coefficient and conductivity measurements a model was deduced, in which the changed electrical properties of the quenched samples are caused by an additional shallow donor and a more complex type of defect which acts – depending on Fermi level – as an acceptor or donor, respectively. An energy level nearer than 0.07 eV to the bottom of the conduction band was estimated for the shallow donor whereas an acceptor level EA = EC − 0.32 eV and a donor level ED = EV + 0.40 eV are connected to the more complicated defect. A migration energy of about 1 eV is ascribed mainly to the shallow donor, which seems also to be responsible for a distinct maximum of defect generation at 1110 °C quenching temperature. According to the given model a dependence of quenched-in defects on the initial doping does not appear to be very important up to net acceptor or donor densities of about 5 × 1015 cm−3. n- und p-leitende Siliziumkristalle wurden von 900 bis 1400 °C in einer Kuhlflussigkeit abgeschreckt. Hall- und Leitfahigkeitsmessungen gaben Anlas zu einem Storstellenmodell, wonach ein zusatzlicher flacher Donator und eine komplexe Storstelle, die je nach Lage des Fermi-Niveaus Akzeptor- oder Donatorverhalten zeigt, die geanderten elektrischen Eigenschaften der abgeschreckten Proben bestimmen. Fur den flachen Donator konnte ein zugehoriges Niveau, das naher als 0,07 eV an der Leitungsbandkante liegt, abgeschatzt werden; mit der komplexen Storstelle werden ein Akzeptorniveau EA = EC − 0,32 eV und ein Donatorniveau ED = EV + 0,40 eV in Verbindung gebracht. Eine Wanderungsenergie EM ≈ 1 eV wird hauptsachlich dem flachen Donator zugeschrieben, ebenso ein ausgepragtes Maximum der Defekt-Erzeugung bei 1110 °C Abschrecktemperatur. Nach dem angegebenen Modell ist eine eventuelle Abhangigkeit der thermischen Fehlstellen von der Ausgangsdotierung bis hinauf zu effektiven Akzeptor- oder Donatorkonzentrationen von ungefahr 5 × 1015 cm−3 bedeutungslos.

The electronic level of interstitial Cr in silicon according to the transition Cr0i→Cr+i(3d6→3d5) was determined by correlating the electron paramagnetic resonance (EPR) signal of Cr+ to Hall measurements on identical samples. The procedure gives the donor level located at Ec −0.222±0.005 eV. From the experiments may be inferred that there is no Cr++i state above Ev +0.05 eV. The solubility of interstitial Cr in silicon is retrograde at 1300° and has a maximum value of 5×1015 cm−3.

An energy level of ${E}_{v}+0.38$ eV related to the 0 to + charge transition of substitutional manganese in silicon has been determined with a combination of deep-level-transient spectroscopy and ESR measurements. There is no evidence for ordinary amphoteric or negative-$U$ behavior in the lower half of the band gap. This is the first identified energy level of a $3d$ substitutional impurity in silicon.

Das 4-Azaheptadien (I) reagiert mit Acrylonitril (II) nicht nach Diels-Alder, sondern unter Michael-Addition zu dem Propenylaminopentannitril (III), das durch Hydrierung, je nach Bedingungen und Katalysator die Piperidine (IV) und Isobutylamin (V) bzw. das Piperidin (VI) und das Isobutylaminopentannitril (VII) liefert; (VII) last sich durch katalytische Hydrierung zu (VI) cyclisieren.

A series of 41 poorly differentiated follicular carcinomas of the thyroid gland without histopathological features of medullary or papillary carcinoma and 9 cases of undifferentiated thyroid carcinoma of the small cell type (diagnosed between 1967 and 1983) were investigated immunohistochemically. Two poorly differentiated follicular carcinomas showed a considerable number of calcitonin-positive cells in addition to the weakly thyroglobulin-positive tumor cells. One of these cases revealed several areas with calcitonin-positive tumor cells with additional squamous metaplasia with keratinization. No medullary carcinomas could be demonstrated among the 9 cases previously diagnosed as undifferentiated thyroid carcinomas of the small cell type. From the epidemiological point of view the application of immunohistochemistry does not significantly increase the proportion of medullary carcinomas detected in our endemic goiter area. The incidence of medullary carcinoma remains surprisingly low when compared with nonendemic areas.

According to the literature synchronous adenocarcinomas of both, the colon and the gallbladder or the colon and the appendix are extremely unusual. To our knowledge the simultaneous occurrence of all three tumors has never been published before. Preoperative diagnosis of early stage tumors of the gallbladder and the vermiform appendix is also made very seldom. The following case report records an instance of synchronous adenocarcinomas of the gallbladder, the transverse colon, in a colonic polyp and the appendix. Owing to the patient's advanced age simultane cancer occurrence may be mere coincidence. Nevertheless, this extremely rare entity could also be ascribed to a genetic defect or an unknown carcinogenic agent.

In total, 15,325 fine needle aspiration (FNA) biopsies of the thyroid were examined in the Department of Pathology of the University of Innsbruck, Austria, between 1976 and 1985, with the cytologic results histologically verified in 3,112 cases. Since (1) it is frequently impossible to distinguish benign from malignant encapsulated follicular thyroid tumors by cytologic criteria and (2) there is a high level of follicular thyroid carcinoma in our endemic goiter area, we have adopted a diagnostic strategy that accepts a high percentage of false-positive cytologic results in order not to miss highly differentiated follicular carcinoma. To avoid unnecessarily extensive surgical treatment, 1,079 intraoperative frozen section examinations of the thyroid were performed in the same time period in (1) patients with preoperative suspicious or positive FNA cytologic findings, (2) cases with suspicious clinical and anamnestic data and (3) tumors with a suspicious macroscopic appearance without preoperative FNA or with negative or unsatisfactory cytologic findings. In 48 cases (4.5%), the frozen section diagnosis had to be revised after examination of paraffin-embedded tissue. An intraoperative false-positive diagnosis was obtained in 3 cases (0.3%) while a false-negative diagnosis was made in 45 cases (4.2%). The main effort in examining frozen sections should be concentrated on avoiding false-positive errors, which can lead to unnecessary thyroidectomies.