Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology

We performed a systematic immunohistochemical study on 378 brain tumors using 37 antibodies and tissue microarray (TMA) technology. The aim of this study was to find new diagnostic biomarkers using antibodies established in our laboratory. Our TMA consisted of a grid of 1.5-mm cores that were extracted from individual donor blocks. Staining for each antibody was scored using a three-point system. We used hierarchical clustering analysis to interpret these data, which resulted in separation of all the brain tumors into seven groups. Although there were some exceptions, cases with the same histological diagnosis were generally grouped together. We then carried out statistical analyses to find the most useful antibodies for grouping of brain tumors. Ten antibodies [glial fibrillary acidic protein (GFAP), Olig2, vimentin, epithelial membrane antigen (EMA), cytokeratin (AE1/AE3), alpha-internexin, nestin, pinealocytes PP5, aquaporin-4 (AQP4) M13d and AQP4M13e] discriminated between astrocytomas and oligodendroglial tumors. Six antibodies [EMA, AE1/AE3, TUJ1, nestin, neurofilament protein-MH (NF-MH) and perivascular cells GP-1] showed significant differences between high-grade and low-grade gliomas. Our data have revealed new antibodies with potential diagnostic utility (Olig2, PP5, GP-1) and demonstrate that TMA technology is highly useful for evaluating newly established antibodies in brain-tumor research.The original publication is available at www.springerlink.co

Effectiveness of a hybrid emergency room system in the management of acute ischemic stroke: a single-center experience

IntroductionHybrid emergency room systems (HERSs) have shown promise for the management of severe trauma by reducing mortality. However, the effectiveness of HERSs in the treatment of acute ischemic stroke (AIS) remains unclear. This study aimed to evaluate the impact of HERSs on treatment duration and neurological outcomes in patients with AIS undergoing endovascular therapy.Materials and methodsThis single-center retrospective study included 83 patients with AIS who were directly transported to our emergency department and underwent endovascular treatment between June 2017 and December 2023. Patients were divided into the HERS and conventional groups based on the utilization of HERSs. The primary outcome was the proportion of patients achieving a favorable neurological outcome (modified Rankin Scale score 0–2) at 30 days. The secondary outcomes included door-to-puncture and door-to-recanalization times. Univariate analysis was performed using the Mann–Whitney U test for continuous variables and the chi-squared test or Fisher’s exact test for categorical variables, as appropriate.ResultsOf the 83 eligible patients, 50 (60.2%) were assigned to the HERS group and 33 (39.8%) to the conventional group. The median door-to-puncture time was significantly shorter in the HERS group than in the conventional group (99.5 vs. 131 min; p = 0.001). Similarly, the median door-to-recanalization time was significantly shorter in the HERS group (162.5 vs. 201.5 min, p = 0.018). Favorable neurological outcomes were achieved in 16/50 (32.0%) patients in the HERS group and 6/33 (18.2%) in the conventional group. The HERS and conventional groups showed no significant difference in the proportion of patients achieving favorable neurological outcomes (p = 0.21).ConclusionImplementation of the HERS significantly reduced the door-to-puncture and door-to-recanalization times in patients with AIS undergoing endovascular therapy. Despite these reductions in treatment duration, no significant improvement in neurological outcomes was observed. Further research is required to optimize patient selection and treatment strategies to maximize the benefits of the HERS in AIS management

Negative correlation between the nuclear size and nuclear Lamina component Lamin A in intraductal papillary mucinous neoplasms of the pancreas

Background: The nuclear laminar protein Lamin A and inner nuclear membrane protein Emerin plays important role in sustaining nuclear structure. However, They have not investigated the significance of these proteins for development of pancreatic intraductal papillary mucinous neoplasm (IPMN).Methods: We examined pancreatic IPMN specimens for nuclear morphology and nuclear protein expression pattern of Lamin A and Emerin. Forty-two IPMN specimens were included, with 30 classified as intraductal papillary mucinous adenoma (IPMA) and 12 as intraductal papillary mucinous carcinoma (IPMC).Results: Classification according to histological subtype revealed that 26 specimens were of the gastric subtype (1 IPMC case), 8 were pancreatobiliary (6 IPMC cases), 6 were intestinal (3 IPMC cases), and 2 were oncocytic (all cases were IPMC). The frequency of IPMN subtypes in this study seemed to agree with those in previous reports. We analyzed Feulgen staining sections for nuclear morphological analysis using computer-assisted image analysis. Nuclear area and perimeter were significantly larger in IPMC than in IPMA. Finally, we examined the positive ratios of Lamin A and Emerin in immunohistochemical staining sections by image analysis. We found a negative correlation between the nuclear size and Lamin A-positive ratio, which was significantly lower in IPMC than that in IPMA. However, no significant correlation was observed between nuclear size and Emerin expression was observed, and no differences were found in the Emerin-positive ratio between IPMA and IPMC.Conclusion: Our results suggest that a decreased Lamin A positive ratio induces nuclear enlargement in adenomas, which thereby induce promotion to carcinomas. Furthermore, Lamin A expression can be a reliable biomarker for distinguishing between IPMC and IPMA

Stereoselective synthesis of functionalized pyrrolidines by the diverted NH insertion reaction of metallocarbenes with β-aminoketone derivatives

A highly stereoselective route to functionalized pyrrolidines from the metal catalyzed diverted N-H insertion of a range of diazocarbonyl compounds with β-aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, copper(I) triflate and an iron(III)porphyrin) are shown to promote the process under mild conditions to give a wide range of highly substituted proline derivatives. The reaction starts with a metallocarbene N-H insertion but is diverted by an intermolecular aldol reaction

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage