Acrania: an autopsy case and review of the literature

ABSTRACT We report an autopsy case of acrania with a review of the literature. A 31-year-old woman was admitted in poor genaral condition and diagnosed as pregnant at the 26th week of gestation. The fetus was suspected to be anencephalic or hydrocephalic by ultrasonography. She delivered a stillbirth male baby at the 28th week of gestation. Autopsy showed the cranium lacked the cranial vault The scalp directly covered the hydrocephalic brain without calvaria. No cerebellum was found macroscopically. On histological examination, the thinned cerebral layer was composed of white matter-like brain tissue with glial and ependymal cells. In the cerebral layer near the base of the skull, a few NSE-positive neurons among many GFAP-positive glial cells and oligodendrocyte-like cells were observed. The choroid plexuses were observed inside the ependymal layers. The brain stem and the spinal cord were normally preserved with clusters of NSE-positive neurons. Agnethia and horseshoe kidney were combined as malformations other than the brain. We reviewed 42 cases of acrania from the literature.     

Mechanical accuracy of a stereotactic irradiation system using a micro multi-leaf collimator

Mechanical accuracy of a stereotactic irradiation system using a micro multi-leaf collimator (mMLC), Elekta DMLC, has been evaluated. Measurements were made to obtain transmission, leakage, penumbra, and positioning accuracy of the DMLC leaf for a 6 MV photon beam. Mechanical accuracy and long term stability of a linac isocenter was also evaluated. The resulting transmission, along a line perpendicular to the leaf movement, was 0.31±0.01%, and the leakage from the closed opposing leaf pairs was 0.39±0.01%. The measured penumbra, at a depth incurring maximum dose, was 2.37±0.16 mm toward the leaf end and 2.14±0.18 mm toward the leaf side for various field sizes. The leaf gap width error, of 0.10±0.08 mm, was obtained by analyzing picket fence test results. The maximum leaf positioning error, of 0.14±0.06 mm, was obtained by analyzing the log file for a various gantry angles during an arc delivery. The isocenter accuracy was within a radius of 1 mm, without any recalibration for two years. In conclusion, our stereotactic irradiation system using DMLC was capable of providing accurate stereotactic treatment.     

Cytotoxicity evaluation of ceramic particles of different sizes and shapes

When artificial hip or knee joints are implanted in the human body, they release metallic, ceramic, and polymeric debris into the surrounding tissues. The toxicity of the released particles is of two types: chemical, caused by the released soluble ions and monomers, and mechanical, a result of mechanical stimulation produced by the insoluble particles. In this study, the cytotoxicity of particles of TiO2, Al2O3, ZrO2, Si3N4, and SiC for murine fibroblasts and macrophages were examined to evaluate just their mechanical toxicity because these particles are not expected to release soluble metal ions. Different sizes and shapes of TiO2 particles were used to evaluate the effect of size and shape on particle cytotoxicity. The results suggest that the cytotoxicity of ceramic particles does not depend on their chemical species. Cytotoxicity levels were lower than those of corresponding metal ions, indicating that the mechanical toxicity of particles is lower than the chemical toxicity of released soluble ions and monomers. The differences in size did not affect the mechanical toxicity of these particles. The dendritic particles had a higher cytotoxicity level for macrophages than did spindle and spheric particles.     

The characteristics of coronary artery revascularization in aged patients

This study was undertaken in order to clarify the clinical characteristic features and surgical results of coronary artery bypass grafting (CABG) in patients over 65 years of age (group III, n=43). These patients were compared with 2 other groups of patients, one aged between 50 and 59 years (group I, n=88) and another aged between 60 and 64 years (group II, n=54), with respect to mortality, morbidity and late survival. CABG was performed with the saphenous vein under cold K-Mg-cardioplegia with systemic hypothermia. The hospital mortality was 2.3, 3.7, and 4.7 per cent in groups I, II and III, respectively, although no operative mortality was noted in any group. The number of coronary artery lesions increased with age, however, the left ventricular ejection fraction was relatively better preserved in the aged patient than in the younger ones. The 5-year survival rates were 93.4, 95.1 and 96.9 per cent in groups I, II and III, respectively, with most of the late deaths occurring within a year after CABG in each group. In the aged patients, postoperative functional recovery was delayed in the liver and kidney, and postoperative psychosis was not infrequent. The results of this study, indicating a low operative mortality and satisfactory late survival rate, thus strongly support CABG for the aged. Nevertheless, the prevention of postoperative complications is also extremely important for reducing hospital mortality.     

Structure-activity relationship of 6-methylidene penems bearing 6,5 bicyclic heterocycles as broad-spectrum beta-lactamase inhibitors: evidence for 1,4-thiazepine intermediates with C7 R stereochemistry by computational methods

The design and synthesis of a series of 6-methylidene penems containing [6,5]-fused bicycles (thiophene, imidazole, or pyrazle-fused system) as novel class A, B, and C beta-lactamase inhibitors is described. These penems proved to be potent inhibitors of the TEM-1 (class A) and AmpC (class C) beta-lactamases and less so against the class B metallo-beta-lactamase CcrA. Their in vitro and in vivo activities in combination with piperacillin are discussed. On the basis of the crystallographic structures of a serine-bound reaction intermediate of 2 with SHV-1 (class A) and GC1 (class C) enzymes, compounds 14a-l were designed and synthesized. Penems are proposed to form a seven-membered 1,4 thiazepine ring in both class A and C beta-lactamases. The interaction energy calculation for the enzyme-bound intermediates favor the formation of the C7 R enantiomer over the S enantiomer of the 1,4-thiazepine in both beta-lactamases, which is consistent with those obtained from the crystal structure of 2 with SHV-1 and GC1.     

Nonsense Mutation at Codon 63 of the BRCA1 Gene in Japanese Breast Cancer Patients

The involvement of abnormalities of the BRCA1 gene in breast cancers in Japanese patients without any family history of this cancer was investigated by polymerase chain reaction-based single-strand conformation polymorphism analysis of the DNA sequences corresponding to the zinc finger domain (exons 2, 3 and 5) and the binding domain with Rad51 (exon 11) of the BRCA1 protein. An identical nonsense mutation at codon 63 (TTA to TAA) was found in 2 of 56 (3.5%) breast cancers from independent patients. The nucleotide change was also detected in the DNAs from non-cancerous tissues of both patients and therefore was a germline mutation. One of the patients was a member of a pedigree involving 3 ovarian cancer and 1 gastric cancer patients, while the other patient had no family history of malignancy. The same germline mutation at codon 63 was reported in four other independent Japanese pedigrees with frequent breast cancer, but not in such families in other countries. These observations suggest that the mutation commonly originated from a single Japanese ancestor. No other mutation of the BRCA1 gene was observed in the samples analyzed in this study. A low incidence of germline mutation and the absence of somatic mutation suggest that the aberration of the BRCA1 gene is involved only in a subset of Japanese breast cancers.     

Simultaneous real-time detection of initiator- and effector-caspase activation by double fluorescence resonance energy transfer analysis

Fluorescence resonance energy transfer (FRET) with green fluorescent protein (GFP) variants has become widely used for biochemical research. In order to expand the choice of fluorescent range in FRET analysis, we designed various color versions of the FRET-based probes for caspase activity, in which the substrate sequence of the caspase was sandwiched by donor and acceptor fluorescent proteins, and studied the potential of these color versions as fluorescent indicators. Six color versions were constructed by a combination of cyan fluorescent protein (CFP), GFP, yellow fluorescent protein (YFP), and DsRed. Real-time monitoring in single cells revealed that all probes could detect caspase activation during tumor necrosis factor (TNF)-alpha-induced cell death as a fluorescent change. GFP-DsRed and YFP-DsRed were as sensitive as CFP-YFP, and CFP-DsRed also showed a large fluorescent change. By using two probes, CFP-DsRed and YFP-DsRed, we carried out simultaneous multi-FRET analysis and revealed that the initiator- and effector-caspases were activated almost simultaneously in TNF-alpha-induced cell death. These findings may give experimental bases for the development of novel techniques to analyze multi-events simultaneously in single cells by using FRET probes in combination.     

Activation of c-Src is inversely correlated with biological aggressiveness of breast carcinoma

In order to investigate whether c-Src is involved in carcinogenesis and progression of breast carcinoma, we examined the expression of activated c-Src in tissue sections from surgically resected human breast specimens. First, we confirmed the specificity of the antibody against activated c-Src (Clone 28) using six cell lines established from human breast carcinomas by western blotting. As expected, activated c-Src was detected as a 60 kDa band in all cell lines tested. Immunofluorescence analysis demonstrated that the activated c-Src was mainly observed in cytoplasms of these cells. Then, we designed an immunohistochemical study with 73 human breast carcinoma tissues. Glandular epithelial and myoepithelial cells in normal mammary glands adjacent to carcinoma nests and infiltrating stromal cells were negative for activated c-Src. In contrast, 37 of the 73 breast carcinoma tested (50.7%) were positive for activated c-Src, and this positive staining was inversely correlated with Ki-67 labeling index (p < 0.0001), TNM stage (p < 0.0001), tumor size (p < 0.0001), and histological grade (p = 0.0002). These results strongly suggest that the activation of c-Src would be related to the progression of breast carcinomas with low aggressiveness.     

High expression of epithelial cellular adhesion molecule in peritoneal metastasis of gastric cancer

Intraperitoneally administrated epithelial cellular adhesion molecule (EpCAM) monoclonal antibody is a therapeutic agent in patients with malignant effusion in several types of carcinoma. However, the role of EpCAM in peritoneal metastasis (PM) lesions and primary lesions of gastric cancer (GC) is still unclear. Therefore, in this study, we investigated EpCAM expression in GC patients with PM. We investigated the expression of EpCAM in 35PM lesions and 104 biopsy samples as primary lesions. Immunohistochemical staining was performed using the Ventana Benchmark XT (Roche Diagnostics) system. EpCAM expression was evaluated by calculating the total immunostaining score, which is the product of the proportion score and the intensity score. Overexpression was defined as a total score greater than 4. All PM specimens showed overexpression of EpCAM, and GC cells in both the surface layer and the deep layer of the PM showed a high expression of EpCAM. Meanwhile, in the biopsy sample, the expression of EpCAM ranged from none to strong. The EpCAM score results for PM specimens and biopsy samples were 11.0?±?2.0 and 6.9?±?3.9, respectively. The difference between the scores was statistically significant (P?<?0.05). The intraperitoneally administrated EpCAM antibody might have a anti-cancer effect in PM lesions of GC. Additionally, it can be assumed that only GC cells which express a high level of EpCAM might metastasize to the peritoneum.     

Cost-effectiveness of treatment of unruptured intracranial aneurysms in patients with a history of subarachnoid hemorrhage

RATIONALE AND OBJECTIVES: The study goal was to evaluate the cost-effectiveness of surgery and endovascular treatment of unruptured intracranial aneurysms in patients with a history of subarachnoid hemorrhage from a previous aneurysm, incorporating the results of the prospective International Study of Unruptured Intracranial Aneurysms. MATERIALS AND METHODS: Using a Markov model, we performed a decision and cost-effectiveness analysis comparing surgery or endovascular treatment with no treatment. Twelve clinical scenarios were defined based on aneurysm size and location. Probabilistic sensitivity analyses were performed for 50- and 40-year-old cohorts. Treatment was considered to be cost-effective at an incremental cost-effectiveness ratio less than $100,000 per quality-adjusted life-year. RESULTS: In 50-year-old patients, no treatment was the most cost-effective strategy for aneurysms located in the cavernous carotid artery. For aneurysms less than 7 mm located in the anterior circulation, no treatment was the most cost-effective strategy. Endovascular treatment was the most cost-effective option for 7- to 24-mm aneurysms, whereas surgery was the most cost-effective option for aneurysms of 25 mm or larger. For aneurysms less than 7 mm and located in the posterior circulation, endovascular treatment was the most cost-effective option, whereas surgery was the most cost-effective option for 7- to 12-mm aneurysms. No treatment was the most cost-effective strategy for aneurysms of 13 mm or larger. CONCLUSION: For 50-year-old patients with a history of aneurysmal subarachnoid hemorrhage, treatment of unruptured aneurysms that are located in the cavernous carotid artery, or small (<7 mm) and located in the anterior circulation, or large (>or=13 mm) and located in the posterior circulation is ineffective or not cost-effective.