Dielectric dispersion measurements were made on dilute solutions of poly(epsilon-carbobenzoxy-L-lysine) in m-cresol; this system underwent a very sharp thermal helix-coil transition of inverse type around 30 degrees. Mean-square dipole moments "mu-2" and mean rotational relaxation times t were obtained as functions of molecular weight and helical fraction fN. It was found that "mu-2"-one-half varied almost linearly with fN-one-half over a substantial portion of the transition. The relaxation times corrected for solvent viscosity and temperature changed only slightly with fN except in the region of small fN, while, at fixed fN, they displayed molecular weight dependence characteristic of rod-like molecules. These results can be explained if the transition is assumed to proceed almost in all-or-none fashion. This assumption is consistent with the previous finding from statistical thermodynamic analyses that the transition of the system PCBL-m-cresol is highly cooperative, with standard deviation of population one-half being 0.0025 to 0.0027, where standard deviation of population is the cooperativity parameter. Application of Nagai's theory of "mu-2" for interrupted helices yielded the result that standard deviation of population-one-half was in the range 0.001 to 0.005 and the monomeric dipole moment in the helical conformation was 5.4 to 6.2 D.

Benzyl Compounds↗

PubMedDate not supplied

Sequential polypeptides. 2. Helix--coil transition in poly(gamma-benzyl epsilon-carbobenzoxy-L-lysyl-L-glutamate).

Helix--coil transitions of an alternating copolypeptide poly(gamma-benzyl epsilon-carbobenzoxy-L-lysyl-L-glutamate) (poly[Lys(Z)-Glu(OBzl)]) in binary mixtures of dichloroacetic acid (DCA) and ethylene dichloride (EDC) were investigated by optical rotatory dispersion (ORD). The ORD data obtained were analyzed to evaluate the equilibrium constant s for helix formation and the cooperativity parameter sigma. The values of sigma1/2 are substantially independent of temperature and solvent composition, yielding 0.4 X 10(-2) on the average. The transition enthalpy deltaHc at the transition point decreases from 291 to 154 cal mol-1 as the DCA content is increased from 56 to 64 vol%. At about 20 degrees C and at 58 vol% DCA, poly[Lys(Z)-Glu(OBzl)] in binary mixtures of DCA and EDC undergoes a solvent-induced transition. This DCA content is intermediate between those for poly(gamma-benzyl L-glutamate) and poly(epsilon-carbobenzoxy-L-lysine) in the same binary solvent and close to that of an equimolar random copolymer of the two peptides. However, the s of poly[Lys(Z)-Glu(OBzl)] is not a geometrical mean of those of the parent homopolypeptides. This fact suggests that the helical conformation of the copolypeptide is stabilized by a conformational induction operative between adjacent residues.

Benzyl Compounds↗

PubMedDate not supplied

Anti-telomerase therapy suppressed glioma proliferation.

In order to determine if telomerase activity contributes to the growth of glioma cells, we constructed an anti-telomerase vector to suppress telomerase expression in glioma cells. The human telomerase (hTR)-antisense vector showed a significant suppression effect. However it did not appear to induce cell death as a stable population of cells survived more than two months following transfection. These results provide evidence that reagents aimed at inhibiting telomerase may represent a useful strategy for suppressing the growth of glioma cells. In addition to telomerase, another mechanism would also maintain telomere length, thus supporting continuous cell proliferation.

Cell Division↗

PubMedDate not supplied

Experimental treatment of malignant gliomas with human monoclonal antibody-drug conjugates.

This study was designed to determine whether the monoclonal antibody-drug conjugates are more potent than the free drugs in killing human glioma cells in vitro and in vivo. The anticancer drugs doxorubicin (DXR) and 4'-epi-doxorubicin (epi-DXR) were separately conjugated to the human monoclonal antibody (mAb) CLNIgG, which binds strongly to human malignant glioma cells. The cytotoxic activity of the mAb-drug conjugates was assessed by a 3H-thymidine assay in vitro. The efficacy, biodistribution and autography of the immunoconuugates were examined using the subcutaneous glioma model (nude mouse). The epi-DXR-CLNIgG conjugate was found to be 11 times more potent than free epi-DXR in killing glioma cells in vitro, and epi-DXR-CLNIgG clearly achieved the most favorable antitumor effects. A biodistribution study using [14-14C]DXR-CLNIgG at the conjugate indicated that the immunoconjugates delivered DXR to glioma tissues at least five times more than the free DXR alone in nude mice without increasing the concentration in other tissues. An autoradiographic study also showed good accumulation of the antibody-drug conjugate in the subcutaneously transplanted glioma. Thus, the human monoclonal antibody-drug conjugates constitute a potential new approach for the treatment of malignant gliomas.

Animals↗

PubMedDate not supplied

Direct cavernous sinus sampling.

To evaluate the potential of superselective cavernous sinus (CS) sampling in patients with functioning pituitary adenomas, we performed direct CS sampling in 18 patients with Cushing syndrome and other functioning adenomas using a mini-catheter. Samples from the inferior petrosal sinuses (IPS) were also obtained. All of the samples from 20 CS of 10 patients with Cushing syndrome and 13 of 16 samples from CS of eight patients with other adenomas were successfully obtained. No complication occurred. In three patients, the mini-catheter was introduced to the contralateral CS through intercavernous communication, and bilateral sampling could be performed via the unilateral jugular vein. The CS/peripheral (CS/P) ratio of ACTH (mean = 66.1) was significantly greater than the IPS/peripheral (IPS/P) ratio (mean = 14.9) in Cushing disease. In other functioning adenomas, the CS/P ratio (15.8) was not significantly higher than the IPS/P ratio (4.8). Direct CS sampling offers a much higher CS/P ratio than IPS/P ratio in Cushing disease, and may provide sufficient diagnostic accuracy without CRH stimulation or bilateral simultaneous sampling.

Adult↗

PubMedDate not supplied

A clinicopathological study of malignant glioma done after local administration of chemotherapeutic agents.

Light and electron microscopic studies on tumor tissue from 5 autopsied and 7 rebiopsied patients with malignant glioma after receiving intratumor administration of anti-neoplastic agents were made. Four patients were correlated with their serial MRI. After craniotomy 0.5 mg of adriamycin was administered using an Ommaya reservoir into the tumor bed. Light microscopy of the recurrent tumor and adjacent necrotic tissue revealed massive coagulation necrosis which was aspirated into the tip of the Ommaya tube. Around the massive coagulation necrosis and cystic cavity, abundant reactive collagenous tissues, gliomesenchymal tissue, infiltrating lymphocytes, and a small amount of foreign body giant cells were found concomitantly with organized necrotic tissue. The electron microscopic study of the above mentioned tissue showed deposits of lipofuscin, lipid droplets, lysosomes in the tissue as well as abundant disintegrated myelin figures and fibrous strands. Furthermore, marked histological necrosis was found mainly at the tip of the Ommaya tube. These morphological findings corresponded to the high signal intensity areas on the gadolinium-enhanced T1-weighted MRI. These facts may indicate that the antineoplastic agents administered directly to a tumor per se cause morphological alternations. Moreover, these facts may suggest a therapeutic effect in the residual tumor cells which would be facilitated by formation of coagulation necrosis and collagenous tissue.

Adult↗