Combination of vinblastine and oncolytic herpes simplex virus vector expressing IL-12 therapy increases antitumor and antiangiogenic effects in prostate cancer models.

Oncolytic herpes simplex virus (oHSV)-1-based vectors selectively replicate in tumor cells causing direct killing, that is, oncolysis, while sparing normal cells. The oHSVs are promising anticancer agents, but their efficacy, when used as single agents, leaves room for improvement. We hypothesized that combining the direct oncolytic and antiangiogenic activities of the interleukin (IL)-12-secreting NV1042 oHSV with microtubule disrupting agents (MDAs) would be an effective means to enhance antitumor efficacy. Vinblastine (VB) was identified among several MDAs screened, which displayed consistent and potent cytotoxic killing of both prostate cancer and endothelial cell lines. In matrigel tube-forming assays, VB was found to be highly effective at inhibiting tube formation of human umbilical vein endothelial cells. The combination of VB with NV1023 (the parental virus lacking IL-12) or NV1042 showed additive or synergistic activity against prostate cancer cell lines, and was not due to increased oHSV replication by VB. In athymic mice bearing CWR22 prostate tumors, VB in combination with NV1042 was superior to the combination of VB plus NV1023 in reducing tumor burden, appeared to be nontoxic and resulted in a statistically significant diminution in the number of CD31(+) cells as compared with other treatment groups. In human organotypic cultures using surgical samples from radical prostatectomies, both NV1023 and NV1042 were localized specifically to the epithelial cells of prostatic glands but not to the surrounding stroma. These data highlight the therapeutic advantage of combining the dual-acting antitumor and antiangiogenic activities of oHSVs and MDAs.

Comparative study of ligand binding during the postsynthetic stabilization of metal oxide nanoparticles.

In the absence of stabilizers in the reaction medium, the nonaqueous synthesis of metal oxide nanoparticles usually results in agglomerated products. Stabilization is however often possible in a postsynthetic treatment, involving the addition of organic ligands that coordinate to the nanoparticle surface. The ligands are commonly expected to chemisorb via functional groups; however, we have recently shown that also weakly and unspecifically interacting ligands can lead to stabilization. Here, we present detailed investigations on the stabilization, comparing the binding of weakly coordinating ligands to a system with strongly and selectively binding stabilizers and additionally exploring the effect of ligand chain length. Although in all cases stabilization and disintegration of agglomerates to the primary particle level are achieved, strong differences are observed with respect to the processes at the particle surface. Moreover, these processes are shown to be more complex than simple ligand adsorption and need to be understood for proper design and choice of stabilizers.

Artificial neural networks for blur identification and restoration of nonlinearly degraded images.

In this paper, an image restoration algorithm is proposed to identify noncausal blur function. Image degradation processes include both linear and nonlinear phenomena. A neural network model combining an adaptive auto-associative network with a random Gaussian process is proposed to restore the blurred image and blur function simultaneously. The noisy and blurred images are modeled as continuous associative networks, whereas auto-associative part determines the image model coefficients and the hetero-associative part determines the blur function of the system. The self-organization like structure provides the potential solution of the blind image restoration problem. The estimation and restoration are implemented by using an iterative gradient based algorithm to minimize the error function.

Reconstruction of thumb in traumatic or congenital loss.

Reconstruction of thumb after traumatic or congenital loss in 17 cases is reported. Cases were divided into three groups according to the level of thumb loss. There were two cases in distal zone, seven in middle and eight in proximal zone. Thirteen cases were traumatic in origin and four had congenital loss. Different reconstruction procedures were used at each level. Osteoplastic reconstruction for the middle zone and index finger pollicization for proximal thumb loss are considered to be most useful methods of thumb reconstruction if microsurgical facilities are not available.

Transfer of latissimus dorsi muscle as myocutaneous flap.

Latissimus dorsi muscle can be transferred as a muscle flap, myocutaneous flap or as a functioning muscle. It can also be used as free muscle or myocutaneous flap. Its long vascular pedicle makes it possible to rotate this muscle through a wide arc of rotation covering neck and upper extremity. It is a large muscle with extensive area and is ideally suited to cover large areas of skin defect. We are reporting eight cases of latissimus dorsi transfer as a myocutaneous flap to cover the skin defects in neck, axilla and upper extremity. Two cases were post-burn and five post-traumatic. One defect was secondary to excision of a large neurofibroma in the area of elbow. Most of the defects at donar sites could be closed primarily. There was only a partial marginal necrosis of transferred tissue in one case. Based upon the knowledge of its vascular anatomy, part of the muscle can be used for transfer which makes the flap less bulky and it can be tailored exactly to the primary defect.

The suitability of 160Tb as a PAC probe for studies of biomolecules.

The gamma-ray perturbed angular correlation (PAC) studies were made with 160Tb as a probe in MES (2[N-morpholino]-ethane sulphonic acid) solutions of various concentrations. The measurements indicate no influence of concentration of the environment on its interaction with Tb3+ ion and as such reveal the fact that 160Tb is not a good probe for PAC studies.

Hypothenar skin grafts for fingertip reconstruction.

Full-thickness skin grafts from the hypothenar area were used to reconstruct 25 digits in a group of 20 patients. The results were evaluated objectively and subjectively at an average of 9.5 months after operation for sensibility, durability, and appearance. Eighty-six percent of the patients had two-point discrimination of 10 mm or less, with one half of them having two-point discrimination of less than 6 mm. All patients had good protective coverage and no ulcer formation. All patients could differentiate between coarse and smooth texture, although only one third had texture discrimination equal to that of normal digits. None of the patients complained of hypersensitivity. The donor site was cosmetically acceptable in all cases. The use of hypothenar full-thickness grafts provides an acceptable method for fingertip reconstruction, particularly in instances of palmar and lateral pulp loss in which there is insufficient tissue available for local advancement.