Karzinomassoziierte Retinopathie (CAR) bei Mammakarzinom und Karzinoid

Fragestellung: Die Karzinomassoziierte Retinopathie (CAR) stellt ein seltenes paraneoplastisches Syndrom dar, das bislang am h?ufigsten bei kleinzelligen Bronchialkarzinomen beschrieben wurde. Wir berichten über 3 Patientinnen mit CAR in Gegenwart eines Mammakarzinoms bzw. eines Karzinoids der Cervix uteri. Patienten und Methode: Es wurden biomikroskopische, perimetrische, angiographische und elektrophysiologische Befunde erhoben. Au?erdem erfolgte eine Testung der Immunreaktivit?t der Seren an humaner Retina. Ergebnisse: Die Befunde umfa?ten ringf?rmige Gesichtsfelddefekte mit statokinetischer Dissoziation und eine pathologische St?bchen- und Zapfenantwort im ERG. Bei 1 Patientin wurde immunhistochemisch eine Reaktion im Bereich der Photorezeptorinnensegmente, der ?u?eren K?rnerschicht sowie der ?u?eren plexiformen Schicht bei fehlendem Nachweis von Antik?rpern gegen Recoverin gefunden. Diskussion: Neben dem kleinzelligen Bronchialkarzinom k?nnen auch andere Prim?rtumoren mit einer CAR vergesellschaftet sein. Der Nachweis von retinalen Autoantik?rpern unterstützt die Annahme einer tumorinduzierten Immunantwort aufgrund der Expression identischer Epitope durch die Tumorzellen. Dabei kommen offensichtlich verschiedene retinale Proteine als Autoantigene in Betracht.      

The effect of comonomer composition, silane heating, and filler type on aqueous TEGDMA leachability in model resin composites

Experimental composites using either bisGMA/TEGDMA or UEDMA/ TEGDMA matrices, quartz or barium glass fillers, and 2 different filler silanization methods were evaluated regarding monomer leachability in distilled water. The leached amount was detected and quantified using gas chromatography. The results showed that twice as much TEGDMA is leached from a bisGMA/TEGDMA based composite than from an UEDMA/ TEGDMA based composite, when both contain 50 wt% TEGDMA. The hypothesis suggested that the higher degree of cure of UEDMA/TEGDMA based composites would be reflected in a lower monomer leaching value, and this hypothesis was supported by the findings. Whether such a correlation exists within groups of UEDMA/TEGDMA based matrices having different degrees of cure was not determined and needs to be investigated in future studies. Variables such as filler composition and silane treatment did not affect the leaching values of TEGDMA in water. That finding suggests that future studies should target differences in matrices, and that the need for considering effects of filler composition and silane treatment methods should not receive the same priority.     

Monitoring left ventricular dilation in mice with PET.

Molecular imaging by small-animal PET is an important noninvasive means to phenotype transgenic mouse models in vivo. When investigating pathologies of the left ventricular (LV) myocardium, the serial assessment of LV volumes is important. By this, the presence of LV dilation as a sign of developing heart failure can be detected. Whereas PET is usually used to derive biochemical and molecular information, functional parameters such as ventricular volumes are generally measured using echocardiography or MRI. In this study, a novel method to monitor LV dilation in mice with PET is presented and evaluated using cardiac MRI. METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin). The volume enclosed by the 3-dimensional midmyocardial contour was calculated as a measure for LV volume for each mouse. Data were compared with ventricular volumes measured by MRI in the same animals. RESULTS: LV volumes obtained by PET and MRI correlated well (R = 0.89) for hearts with small and large left ventricles. In accordance with the hypothesis, the LV volumes were increased significantly for transgenic mice examined at an older age compared with those examined at a younger age (MRI: 160.5 +/- 25.7 microL vs. 114.7 +/- 15.2 microL [P = 0.012]; PET: 129.3 +/- 15.3 microL vs. 73.8 +/- 15.0 microL [P < 0.001], all values shown as mean +/- SD; for MRI, mean of end-diastolic and end-systolic volumes are given), whereas they did not for their wild-type littermates (MRI: 106.2 +/- 12.3 microL vs. 94.7 +/- 14.6 microL [P = 0.214]; PET: 82.6 +/- 20.9 microL vs. 65.0 +/- 16.9 microL [P = 0.185]). CONCLUSION: Evaluation and quantitation of LV dilation in both control and cardiomyopathic mice can be reliably and serially performed using small-animal PET and (18)F-FDG, yielding useful functional information in addition to metabolic data.     

Phage-displayed recombinant single-chain antibody fragments with high affinity for cholesteryl ester transfer protein (CETP): cDNA cloning, characterization and CETP quantification.

Cholesteryl ester transfer protein (CETP) greatly affects the metabolism of all lipoprotein classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL), both known to constitute powerful risk factors for coronary artery disease (CAD). We now report the successful first cloning and characterization of single-chain antibody fragments specific for CETP. A recombinant phage display library was generated using spleen mRNA isolated from BALB/c mice that had been immunized with highly purified CETP. Screening of the library yielded two single-chain antibody fragments with high affinity for CETP, termed 1CL8 and 1CL10, displaying respective KD values of 4.36 x 10(-9) M and 4.64 x 10(-9) M as determined by affinity sensor technology. Amino acid sequence comparison indicated the complementarity-determining regions of the respective heavy chains to be responsible for CETP high affinity binding. Fragment 1CL8 was successfully employed in clinical chemical quantification systems that uncovered an association in humans between plasma CETP concentration and total body fat mass (r=0.50, p<0.002). Because of the demonstrated superb CETP capturing capacity, combined with high binding affinity to CETP, ready access and unlimited supply, 1CL8 and 1CL10 are expected to prove powerful tools for studies on the role of CETP in atherogenesis.     

Long-Term Subdural Strip Electrocorticographic Monitoring of Ictal Déjà Vu

Summary: We report a series of 8 patients with ictal déjà vu. Subdural strip electrocorticographic (ECoG) monitoring localized the ictal epileptogenic focus as follows: right (n = 6) and left (n = 2) mesiotemporal lobe. In all 8 patients, the left hemisphere was dominant for language function based on intracarotid amytal testing. In 6 right-handed patients, ictal déjà vu was associated with a right temporal lobe focus. However, in the 2 left-handed patients, the ictal focus was left temporal lobe. Although ictal déjà vu localizes the epileptic focus to temporal lobe, this experiential phenomenon appears to lateralize to the hemisphere nondominant for handedness.     

Zur Acylierung von Hydroxy- und Mercapto-carbonsäureestern nach dem Carbodiimid/Acylierungskatalysator-Verfahren

On the Acylation of Hydroxy- and Mercaptocarboxylic Acid Esters Using the Carbodiimide/Acylation Catalyst Method Acylation of esters of hydroxycarboxylic acids can be carried out easily and in good yields by using the carbodiimide/acylation catalyst method. The reaction has also been applied to dihydroxy- and mercaptocarboxylic acid esters. The compounds formed from certain esters of hydroxycarboxylic acids are unstable to heat and decompose easily to the free carboxylic acid. No racemization is observed when using enantiomeric hydroxycarboxylic acids. Use of racemic carboxylic acids leads to diastereomers, whose ¹H-NMR shifts for characteristic protons are different as expected. Five drugs are among the carboxylic acids investigated in this context.     

Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro

Summary Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.Dedicated to Prof. Dr. H. J. Dengler on the occasion of his 65th birthday. This study was supported by the Ministry of Science and Research of Nordrhein-Westfalen     

Recombinant human IL-16 inhibits HIV-1 replication and protects against activation-induced cell death (AICD)

The chemoattractant cytokine IL-16 has been reported to suppress lymphocyte activation and to inhibit HIV-1 replication in acutely infected T cells. We have cloned and expressed human IL-16 in Escherichia coli and investigated whether the recombinant protein could regulate the level of lymphocyte apoptosis from HIV-1-infected subjects. After purification and refolding, only 2–10% of the recombinant cytokine was present in a biologically active homotetrameric form. This could explain the need for high concentrations of the bacterially derived IL-16 to induce significant inhibition of HIV-1 replication. Addition of IL-16 to unstimulated peripheral blood mononuclear cell (PBMC) cultures from HIV-1-infected subjects did not modify the observed level of spontaneous lymphocyte apoptosis. In contrast, IL-16 added to PBMC cultures stimulated with anti-CD3, anti-CD95 or dexamethasone reduced significantly the percentage of lymphocytes undergoing AICD. This effect was found to correlate with the ability of the cytokine to decrease CD95 expression on activated CD4⁺ T cells. Comparative studies on PBMC from healthy individuals indicated that the regulation of apoptosis levels by IL-16 is a complex phenomenon and could depend on the nature of the activator used and/or the immune status of lymphocytes tested. The outcome of CD4 cross-linking on T cells by various ligands is discussed in the context of the observed beneficial activities of IL-16 and its potential role in the treatment of HIV disease.