Investigating chiral morphogenesis of gold using generative cellular automata.

Homochirality is an important feature in biological systems and occurs even in inorganic nanoparticles. However, the mechanism of chirality formation and the key steps during growth are not fully understood. Here we identify two distinguishable pathways from achiral to chiral morphologies in gold nanoparticles by training an artificial neural network of cellular automata according to experimental results. We find that the chirality is initially determined by the nature of the asymmetric growth along the boundaries of enantiomeric high-index planes. The deep learning-based interpretation of chiral morphogenesis provides a theoretical understanding but also allows us to predict an unprecedented crossover pathway and the resulting morphology.

Evolution of acute lacunar lesions in terms of size and shape: a PICASSO sub-study.

The imaging definition of lacunar infarcts is variable, particularly regarding their size and the presence of cavitation. We investigated the changes of diameter and evolution pattern of acute lacunar infarcts, and the factors associated with the evolution pattern. Patients with acute single subcortical hemispheric or brainstem ischemic lesions of penetrating arterial territories were included. Maximal diameters on initial diffusion-weighted image (DWI) and follow-up fluid-attenuated inversion recovery image (FLAIR), which performed > 12 months after initial DWI, were semi-automatically measured. Clinical characteristics were compared according to evolution patterns on follow-up FLAIR, classified as cavitated, focal lesion without cavitation, and disappeared. Five hundred nine patients were included. Mean time to follow-up was 31.3 ± 13.7 months. Mean diameter of acute lacunar lesions decreased from 12.9 ± 4.4 to 8.5 ± 4.8 mm during follow-up. Lesions of 58.2% patients remained as cavitated, 18.3% as focal lesion without cavitation, and 23.6% disappeared. Initial NIHSS score (p = 0.005), diameter of initial lesion (p < 0.001), number of slices showing acute lesion on DWI (p < 0.001), progression of white matter lesion (p < 0.001), number of acute lesions involving gray matter (p = 0.008) and lesion location (p < 0.001) were different among three groups. After adjustment for covariates, diameter of the acute lesion, initial number of old lacunes, and anterior lesion location were associated with the appearance of cavitation. Initial lesion diameter and posterior lesion location were associated with the disappearance. We observed reduction of the acute lacunar lesion diameter in 86%. There were predictive factors of disappearance and cavitation of acute lacunar infarction.

Contrast-Enhanced Color-Coded Doppler Sonography in Moyamoya Disease: A Retrospective Study.

The purpose of this study was to validate the feasibility of contrast-enhanced transcranial Doppler sonography (CE-TCCD) in the diagnosis of Moyamoya disease (MMD). CE-TCCD data on patients with MMD were analyzed. The CE-TCCD data were classified qualitatively into four patterns by two independent investigators: normal vascular color Doppler signal (pattern 1), augmented color Doppler signal with identifiable vascular structure (pattern 2), confluent color Doppler signal filling more than two-thirds of the display frame without identifiable vascular structure (pattern 3) and confluent color Doppler signal filling full display (pattern 4). To investigate the validity, we compared the CE-TCCD data with traditional transcranial Doppler data and Suzuki grades on cerebral angiography. A total of 32 CE-TCCD studies from 16 MMD patients (male 37.5%, median age 48) were included in this study. The CE-TCCD findings were distributed across patterns 1 (n = 3), 2 (n = 12), 3 (n = 10) and 4 (n = 7) and were correlated with the Suzuki grades (p <0.005) and hemodynamic parameters. Inter-rater reliability was promising (Cronbach α = 0.883). The CE-TCCD test provides distinctive patterns in MMD, according to their stage of progression. CE-TCCD patterns seem to be a reliable and valid means for the evaluation of MMD.

Intracavitary radiation therapy for recurrent cystic brain tumors with holmium-166-chico : a pilot study.

OBJECTIVE: Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. METHODS: Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. RESULTS: There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. CONCLUSION: Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

Tumor targeting of humanized fragment antibody secreted from transgenic rice cell suspension culture.

The tumor-associated glycoprotein 72 (TAG 72) has been shown to be expressed in the majority of human adenocarcinomas. In an effort to develop a technique for the safe and inexpensive production of large quantities of anti-TAG 72 humanized antibody fragments (hzAb) as a future source of clinical-grade proteins, we developed a transgenic rice cell suspension culture system. The in vivo assembly and secretion of hzAb were achieved in a transgenic rice cell culture under the control of the rice alpha amylase 3D (RAmy 3D) expression system, and the biological activities of plant-derived hzAb were determined to be quite similar to those of animal-derived antibody. Purified hzAb was shown to bind to the recombinant antigen, TAG 72, and to bind specifically to human LS 174T colon adenocarcinoma cells expressing the TAG 72 antigen, and this binding occurred to the same extent as was seen with animal-derived antibody. Plant-derived hzAb proved as effective as animal-derived antibody in targeting tumors of xenotransplanted LS 174T cells in nude mice. The results of this study indicate that the hzAb derived from plant cell suspension cultures may have great potential for pharmaceutical applications in the development of future cancer therapeutic and diagnostic protocols.

A comparative study of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA: preparation and in vivo evaluation in nude mice xenografted with a neuroendocrine tumor.

UNLABELLED: Dimercaptosuccinic acid (DMSA) exists in meso and racemic (rac) forms. Unlike a meso isomer, rac-2,3-DMSA is very soluble in water, strongly acidic solutions and organic solvents. Despite these differences, rac-2,3-DMSA has not been studied as a radiopharmaceutical. In this study, (188)Re complexes with diastereomeric DMSA were prepared to compare the properties of 188Re(V)-rac-DMSA with those of 188Re(V)-meso-DMSA in in vitro and in vivo models. METHODS: rac-2,3-DMSA was synthesized and radiolabeled with 188Re. The biodistribution and gamma camera imaging of 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA were performed in nude mice subcutaneously implanted with PC-12 cell lines. RESULTS AND CONCLUSIONS: Both 188Re(V)-meso-DMSA and 188Re(V)-rac-DMSA showed excellent radiochemical purity and stability at room temperature. Compared with 188Re(V)-meso-DMSA, 188Re(V)-rac-DMSA needed a higher concentration of rac-DMSA and metabisulfite for maximum yields. 188Re(V)-meso-DMSA showed high labeling efficiency at pH 2, whereas 188Re(V)-rac-DMSA showed maximum yields at pH 5. The tumor uptake of 188Re(V)-rac-DMSA was 3.5 times higher than that of 188Re(V)-meso-DMSA at 1 h (P<.01). Gamma camera images showed that 188Re(V)-rac-DMSA was more selectively localized than 188Re(V)-meso-DMSA at the tumor region in a xenograft model. These results demonstrate that 188Re(V)-rac-DMSA may have better potential than 188Re(V)-meso-DMSA as a therapeutic agent against neuroendocrine tumors.

Overexpression of Glut1 in lymphoid follicles correlates with false-positive (18)F-FDG PET results in lung cancer staging.

UNLABELLED: The evaluation of mediastinal lymph node involvement in non-small cell lung carcinoma (NSCLC) is very important for the selection of surgical candidates. PET using (18)F-FDG has remarkably improved mediastinal staging in NSCLC. However, false (18)F-FDG PET results remain a problem. This study was undertaken to identify histologic and immunohistochemical differences between cases showing false and true results of mediastinal lymph node involvement assessed by (18)F-FDG PET. METHODS: Preoperative (18)F-FDG PET examinations were performed on 62 patients with NSCLC, and mediastinal lymph node sampling was done at thoracotomy or mediastinoscopy. In 111 lymph nodes, the size, glucose transporter 1 (Glut1) expression, grade of follicular hyperplasia, and involved proportion of tumor were examined and compared with the (18)F-FDG PET findings. RESULTS: Lymphoid follicular cells were strongly positive for the expression of Glut1. The grade of follicular hyperplasia in false-positive lymph nodes was higher than that in true-negative nodes (P < 0.001). The Glut1 expression of metastatic tumors was higher in true-positive nodes than that in false-negative nodes (P < 0.001). Metastatic squamous cell carcinomas showed stronger Glut1 expression than adenocarcinomas and no false-negative results on (18)F-FDG PET. On the other hand, metastatic adenocarcinomas exhibited focal and weak Glut1 expression with frequent false-negative results. CONCLUSION: The results of this study indicate that (a). lymphoid follicular hyperplasia with Glut1 overexpression may have a causal relationship with high (18)F-FDG uptake of false-positive nodes and (b). the lower expression of Glut1 in metastatic tumors, such as adenocarcinomas, might be responsible for false-negative lymph nodes.

Detection of early recurrence with 18F-FDG PET in patients with cervical cancer.

UNLABELLED: This study investigated the feasibility of PET with (18)F-FDG to evaluate retrospectively early recurrence in patients with cervical cancer. METHODS: From September 1997 to March 2000, 249 patients with no evidence of cervical cancer after treatment were investigated with (18)F-FDG PET. (18)F-FDG PET scanning, beginning 50 min after injection of 370-555 MBq (18)F-FDG, was performed. (18)F-FDG uptake other than physiologic uptake was evaluated with the standardized uptake value and was analyzed by 2 observers who were unaware of CT or MRI data. CT or MRI and needle biopsies were performed to evaluate the positive lesions on (18)F-FDG PET, and all patients were monitored closely for 6 mo for recurrence. RESULTS: Of the 249 patients, 80 patients (32.1%) showed positive lesions with (18)F-FDG PET, and 28 patients (11.2%) were clinically or histologically confirmed as having recurrences. Eighty-two percent of recurrence was detected within 6-18 mo after diagnosis, and 89% of recurrence occurred in Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stage IIb and stage III patients. The sensitivity and specificity of (18)F-FDG PET for detection of early recurrence were 90.3% and 76.1%, respectively. The sensitivity of (18)F-FDG PET was high in mediastinal, hilar, and scalene lymph nodes, spine, and liver; however, the sensitivity was relatively low in lung, retrovesical lymph nodes, and paraaortic lymph nodes. Three false-negative cases were detected in lung, retrovesical lymph nodes, and paraaortic lymph nodes. CONCLUSION: (18)F-FDG PET was effective in detecting early recurrences in cervical cancer patients with no evidence of disease. (18)F-FDG PET may be a useful follow-up method for cervical cancer, thereby providing the patients with early opportunities for sophisticated treatments.

Monte Carlo dose simulation for intracoronary radiation therapy with a rhenium 188 solution-filled balloon with contrast medium.

BACKGROUND: The therapeutic efficacy of percutaneous transluminal coronary angioplasty is limited by the incidence of restenosis. Intracoronary irradiation has shown to be effective in restenosis control by inhibiting the neointimal proliferation. METHODS AND RESULTS: Monte Carlo simulation has been performed to calculate the dose to the vessel wall for intracoronary irradiation with a rhenium 188 solution-filled balloon for restenosis inhibition. With a 3-mm-diameter and 30-mm-long balloon, the radiation dose at 1 mm from the balloon surface was 5.3% lower when the balloon structure was included in geometric modeling of the angioplasty catheter, as compared with that obtained by ignoring the structure. The additional dose reduction due to Hexabrix 320 contrast medium added in 30% of volume ratio was 4.7%. With regard to axial dose distribution, the dose was uniform over the balloon length except near the balloon end, at which the dose was reduced by 35% at a 1-mm-deep layer in the vessel wall. With the Re-188 solution mixed with 30% of Hexabrix 320 in volume ratio, the Re-188 activity to be injected for delivery of 15 Gy to the 1-mm-deep layer by 1-minute irradiation was 27.3 GBq/mL. CONCLUSIONS: Dose estimates produced in this study should be helpful in determining the Re-188 activity to be injected or the irradiation time for a varying situation in terms of length and diameter of the irradiated arterial segment and depth of the target layer.