The affinity of an oligodeoxynucleotide-peptide conjugate for an RNA hairpin loop depends on stereochemistry at the DNA-peptide junction

Molecular models of an oligodeoxynucleotide-peptide conjugate complexed to an RNA hairpin loop were constructed to assess the effect of stereoisomerism at the point of attachment of the peptide to the oligodeoxynucleotide on the affinity of the conjugate for an RNA target. The peptide portion of the oligodeoxynucleotide-peptide conjugate, (L-lysine)8, was covalently attached to the N-allyl group of (D)- or (L)-aspartic alcohol that was incorporated into the interior of an antisense oligodeoxynucleotide. The stereocenter in the oligodeoxynucleotide interior originates from either (D)- or (L)-aspartic alcohol. The oligodeoxynucleotide portion of the oligodeoxynucleotide-peptide conjugate forms Watson-Crick base pairs with the single-stranded RNA that flanks the RNA hairpin loop. The positively charged peptide makes specific electrostatic contacts with the negatively charged phosphate backbone of the RNA hairpin loop when attached to the N-allyl of (D)-aspartic alcohol but does not have the proper orientation to make these electrostatic contacts when attached to the N-allyl of (L)-aspartic alcohol. This modelling study emphasizes the importance of stereocontrol at the point of branching in synthesizing oligodeoxynucleotide-peptide conjugates for binding of RNA hairpin loops.     

Noninvasive assessment of regional ventilation in the human lung using oxygen-enhanced magnetic resonance imaging

The imaging of regional ventilation in the lungs is essential for the evaluation of a variety of pathological conditions, such as emphysema, pneumonia and pulmonary embolism. We propose a novel approach for ventilation scanning, using magnetic resonance imaging (MRI) and inhaled molecular oxygen as a contrast agent, that directly depicts transfer of oxygen across the alveolus into the pulmonary vasculature. Molecular oxygen is only weakly paramagnetic but produces substantial signal changes in the lungs because of their large surface area. Ventilation defects were shown in a patient with bullous emphysema, and ventilation-perfusion mismatches were shown in two patients with pulmonary embolism.     

Fine needle aspiration cytologic findings in malignant small cell tumor of the thoracopulmonary region (Askin tumor)

From 1980 to 1992, five cases of Askin tumor were diagnosed by fine needle aspiration cytology at the Shiraz University Hospitals, Namazi, Faghihi and Beheshti, Iran. All patients were female, their ages ranging between 15 and 22 years. Three of them had a mass on the right side and two on the left side of the chest. Chest roentgenography revealed no bone involvement. Two tumors involved the lungs and pleura. Urinary catecholamine levels were within normal limits. The fine needle aspiration smears revealed many small, round malignant cells with indistinct cytoplasm, a high nuclear/cytoplasmic ratio and prominent, multiple nucleoli. Homer-Wright rosettes were seen frequently. The cells were often arranged in rows simulating rouleaux formation. They were positively stained by periodic acid-Schiff stain. The histologic sections confirmed the cytologic diagnosis of Askin tumor. Four of the patients died within 7-11 months after treatment began.     

Progressive systemic sclerosis: intrathecal pain management

PURPOSE: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. METHODS AND MATERIALS: The organ distribution of 3H lucanthone in mice and 125I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. RESULTS: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. CONCLUSION: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536.     

The function of the reproductive system in x-ray-irradiated male rats after the transplantation of a culture of testicular cells from newborn piglets

The effect exerted by transplantation of the 5 day culture of testicles from newly born piglets on the hypogonadal state of mature X-ray irradiated (3 Gy) rats was studied. It has been found that a month after transplantation (two months after irradiation) the hypogonadal state disappeared for a while, which is confirmed by normalization of the weight of seminal vesicles, content of testosterone and biologically active lutropine, restoration of the reproductive function of rats. No significant changes in steroidogenesis activity have been found, which proves a substituent character of transplantation. The effect disappears three months later but certain restoration of the content of nucleic acids in the testicles is observed.