A new antisense oligonucleotide delivery system based on self-assembled ODN-PEG hybrid conjugate micelles.

The conjugate of antisense c-raf oligonucleotide (ODN) and poly(ethylene glycol) (PEG) was synthesized for intracellular ODN delivery. When combined with polyethylenimine (PEI), the ODN-PEG conjugate self-associated to form polyelectrolyte complex micelles in aqueous solution. The effective hydrodynamic diameter of the micelles was ca. 70 nm with a narrow size distribution. Flow cytometry analysis indicated that the cellular uptake of the micelles by A2780 cells was much higher than that of ODN alone. The micelles also showed a superior antiproliferative activity against ovarian cancer cells in vitro and in vivo.     

Myoepitheliomas of the soft palate: helical CT findings in two patients.

We describe the enhancement patterns of myoepithelioma in two patients with a soft palate mass. In the first case, helical CT revealed a faintly enhancing mass. Histologically, the tumor was composed of plasmacytoid cells in a background of rich myxoid stroma. Immunostaining for CD34 showed scanty blood vessels. In the second case, helical CT revealed an intensely enhancing mass. Histologically, the mass was a cellular tumor with fibrous stroma. Immunostaining for CD34 also showed frequent blood vessels.     

Statistical MUNE: A comparison of two methods of setting recording windows in healthy subjects and ALS patients

OBJECTIVE: To address the issue as to how best to perform statistical MUNE, we applied two different approaches and compared results in healthy subjects and ALS patients. METHODS: Twelve normal subjects (women 8, mean age 52years) and 11 ALS patients (women 4, mean age 54years) underwent two consecutive MUNE studies, which differed in terms of setting and modifying the recording window. These are referred to as the 'expansion' and 'narrowing' methods, respectively. Size-weighted average (Av) SMUP and MUNE values were obtained using the two methods, and compared in control and patient groups. RESULTS: Expansion method-derived Av SMUP sizes and MUNE values differed only slightly from those obtained using the narrowing method in healthy subjects, whereas the narrowing method resulted in significantly larger Av SMUP sizes and smaller MUNE values than the expansion method in ALS patients (Wilcoxon signed ranks test, p=0.003). The sizes of tested areas (mean+/-SD) were significantly larger for the narrowing method than the expansion method in both subject groups with much greater difference in ALS patients; 9.6+/-3.1% vs. 7.9+/-1.7% in healthy subjects and 16.1+/-5.1% vs. 11.2+/-3.0% in ALS patients (Student t-test, p<0.01). CONCLUSIONS: The present study shows, unlike that found in normal subjects, that the results of statistical MUNE in ALS patients are heavily dependent on the approach used to set and modify recording windows. SIGNIFICANCE: The expansion method using a 10%-sized window is likely to suffer from systemic errors due to the ceiling effect and the sampling of artifactually small motor units in ALS patients. The authors recommend that the narrowing method be considered as an alternative that avoids these problems.     

Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic ultrasonography.

OBJECTIVE: To evaluate the pattern of contrast enhancement with Levovist on coded harmonic angiographic ultrasonography of hepatic hemangiomas. METHODS: Twenty hemangiomas were evaluated with coded harmonic angiographic ultrasonography and a microbubble contrast agent. Verification of the diagnosis of a hemangioma was made by means of dynamic computed tomography (n = 8), dynamic magnetic resonance imaging (n = 1), radionuclide scanning (n = 6), or follow-up ultrasonography (n = 5). Ultrasonographic images were obtained before contrast agent administration and with a bolus injection of 2.5 g of a microbubble contrast agent (300 mg/mL Levovist; Schering AG, Berlin, Germany) every 10 to 15 seconds for 5 minutes. The contrast enhancement patterns of the 20 hemangiomas were assessed. RESULTS: The tumor diameters as measured on ultrasonography were 7 to 97 mm (mean, 26.7 mm). Of the 20 hemangiomas, peripheral globular enhancement with progressive centripetal fill-in was shown in 15 (75%), rimlike enhancement with progressive centripetal fill-in was shown in 2 (10%), and homogeneous enhancement was shown in 1 (5%). In the remaining 2 lesions (10%), the enhancement patterns could not be seen, because they were not found on coded harmonic angiographic ultrasonography. CONCLUSIONS: Coded harmonic angiographic ultrasonography with a microbubble contrast agent can depict the typical enhancement pattern in most hepatic hemangiomas.     

Clinical utility of trapezius muscle studies in the evaluation of amyotrophic lateral sclerosis.

Needle electromyography (EMG) and determining the motor evoked potential (MEP) of the genioglossus (tongue) are difficult to perform in evaluation of the craniobulbar region in patients with amyotrophic lateral sclerosis (ALS). Needle EMG and MEP determination in the upper trapezius were carried out in 17 consecutive ALS patients. The needle EMG parameters recorded included abnormal spontaneous activity and motor unit action potential morphology. An upper motor neuron lesion was presumed when either response to cortical stimulation was absent, or the central conduction time was delayed (>mean + 2 SD). Of the 12 patients with limb-onset ALS, using needle EMG, 11 were found to have abnormalities in the upper trapezius, and only five in the tongue. Three of the six patients with isolated limb involvement had abnormal MEP findings. In conclusion, electrophysiological studies of the upper trapezius are useful in ALS patients without bulbar symptoms.     

EXAMINATION OF DEVELOPMENTAL NEUROTOXICITY BY THE USE OF TISSUE CULTURE MODEL SYSTEMS

1. The rotation-mediated three-dimensional reaggregate culture system is uniquely suited for studies on developmental neurotoxicity. In this system, it is possible to reconstruct central neuronal pathways and follow their development. 2. Exposure to drugs of abuse including methamphetamine and methylenedioxyamphetamine or the appetite suppressant, fenfluramine, reduces monoamines in the cultures in a dose-dependent manner and interrupts normal monoaminergic development. 3. While the monoaminergic neurones may attain normal rates of development following drug removal, the affected neurones are not capable of overcoming the drug-induced insults and a deficiency in monoamines persists throughout development. 4. In addition, the production of immortalized monoclonal hybrid cells obtained by fusion of fetal mesencephalic neurones with a neuroblastoma has yielded cell lines expressing a dopaminergic phenotype. 5. Such cells have been useful in establishing the relationship of neurotoxicity to cell lineage and can serve as models for the study of the cellular and molecular mechanisms of neurotoxicity.