Pathologic features of ulegyria in refractory epilepsy by modified anatomic hemispherectomy: a clinicopathologic study of 39 cases / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic features of the brain tissue diagnosed as ulegyria from modified anatomic hemispherectomy for refractory epilepsy.</p><p><b>METHODS</b>The clinical and pathologic findings were reviewed in 39 patients who underwent modified anatomic hemispherectomy and diagnosed as ulegyria in the Epilepsy Center of Tsinghua University Yuquan Hospital from 2007 to 2011.</p><p><b>RESULTS</b>All patients including 30 males and 9 females had medically intractable seizures, and the mean age of seizure onset and disease duration were 4.0 years and 7.3 years respectively. Significant history included febrile seizure in 14 patients (35.9%), cerebral hemorrhage in 8 patients (20.5%), fetal distress and surgical trauma each in 6 patients (15.4%), vascular malformation and cerebral hemorrhage in 1 patient (2.6%), and unclear history in 4 patients (10.2%). Histologically, all cases were characterized by cortical destruction, with neuronal loss and gliosis. All cases were accompanied by varying degree of cortical dysplasia, which were diagnosed as focal cortical dysplasia IIId. Hippocampus sclerosis was identified in 2 cases. Seizure outcome after surgery revealed 37 patients (94.9%) had an Engel grade I, two patients (5.1%) had an Engel grade II.</p><p><b>CONCLUSIONS</b>Febrile seizure, cerebral hemorrhage, fetal distress and surgical trauma in childhood can lead to refractory epilepsy. Histopathological change in the brain is ulegyria accompanied by focal cortical dysplasia IIId. Modified anatomic hemispherectomy is an effective therapy to treat those patients with extensive changes of one hemisphere.</p>

Virtual mutagenesis of isocitrate dehydrogenase 1 involved in glioblastoma multiforme / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Site A132Arg mutations potentially impair the affinity of isocitrate dehydrogenase 1 (IDH1) for its substrate isocitrate (ICT), consequently reducing the production of α-ketoglutarate and leading to tumor growth through the induction of the hypoxia-inducible factor-1 (HIF-1) pathway. However, given that the roles of other active sites in IDH1 substrate binding remain unclear, we aimed to investigate IDH1 mutation pattern and its influence on enzyme function.</p><p><b>METHODS</b>Fifteen IDH1 catalytic active site candidates were selected for in silico mutagenesis and protein homology modeling. Binding free energy of the IDH1/ICT complexes with single-site mutations was compared with that of the wild type. The affinity of 10 IDH1 catalytic active sites for the ICT substrate was further calculated.</p><p><b>RESULTS</b>The IDH1 active site included seven residues from chain A (A77Thr, A94Ser, A100Arg, A132Arg, A109Arg, A275Asp, and A279Asp) and three residues from chain B (B214Thr, B212Lys, and B252Asp) that constituted the substrate ICT-binding site. These residues were located within 0.5 nm of ICT, indicating a potential interaction with the substrate. IDH1 changes of binding free energy (ΔE) suggested that the A132Arg residue from chain A contributes three hydrogen bonds to the ICT α-carboxyl and β-carboxyl groups, while the other nine residues involved in ICT binding form only one or two hydrogen bonds. Amino acid substitutes at A132Arg, A109Arg, and B212Lys sites, had the greatest effect on enzyme affinity for its substrate.</p><p><b>CONCLUSIONS</b>Mutations at sites A132Arg, A109Arg, and B212Lys reduced IDH1 affinity for ICT, indicating these active sites may play a central role in substrate binding. Mutations at sites A77Thr, A94Ser, and A275Asp increased the affinity of IDH1 for ICT, which may enhance IDN1 catalytic activity. Mutant IDH1 proteins with higher catalytic activity than the wild-type IDH1 could potentially be used as a novel gene therapy for glioblastoma multiforme.</p>

Construction and identification of RNA interference lentiviral expression vector of galectin-3 gene / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a recombinant lentiviral U6 plasmids for RNA interference (RNAi) of galectin-3 gene and select the optimal target sequence of galectin-3 gene for RNAi.</p><p><b>METHODS</b>Double-stranded oligo DNAs were designed and synthesized according to the sequence of galectin-3 gene, and ligated into linearized pGCL-GFP/U6 plasmid followed by transformation into competent DH5alpha cells. After PCR and sequence analysis for verification of the positive clones, the plasmid pGCL-GFP/U6 Gal-3shRNA-1 was extracted and transfected into CaCl2-treated 293T cells to obtain the viral vectors containing the RNAi sequence. MCF-7 cells were infected with pGCL-GFP/U6 Gal-3shDNA-1, and at the infection rate over 50%, the cells were harvested to extract the RNA. Real time-PCR was performed to determine the expression level of galectin-3 mRNA in the infected cells.</p><p><b>RESULTS</b>The recombinant vector was successfully constructed as confirmed by sequence analysis. High titer of the virus was obtained, and after infection of MCF-7 cells, RNAi targeting the 1# and 3# sequences in galectin-3 gene resulted in suppression of galectin-3 mRNA expression by 95% and 85%, respectively.</p><p><b>CONCLUSION</b>The recombinant lentiviral U6 plasmid for RNAi of Galectin-3 gene has been successfully constructed, which provides the basis for further study of the role of galectin-3 gene in tumor cells.</p>

Clinical pathology, diagnosis, and treatment of mixed growth hormone-and prolactin cell adenoma / 中国医学科学院学报

<p><b>OBJECTIVE</b>To discuss the clinical pathology and management of mixed growth hormone- and prolactin (GH-PRL) cell adenoma.</p><p><b>METHOD</b>Eight patients (4 men and 4 women, with the mean age of 32.3 year old and duration of symptoms 12 months) underwent examination of serum endocrine and magnetic resonance imaging. Clinical manifestations included headache, physiognomy of acromegalic patient, large pudgy hands and foots, menstrual dysfunction, amenorrhea, galactorrhea, and descending vision. Patients underwent transsphenoidal microsurgery of mixed GH-PRL pituitary adenoma between 1986 and 2004.</p><p><b>RESULTS</b>The hypersecretion of GH and PRL was relieved after operation. Headache was obviously improved in all patients. In 5 cases the menstrual dysfunction and amenorrhea were recovered. In 4 cases the galactorrhea and descending vision disappeared.</p><p><b>CONCLUSIONS</b>The diagnosis of mixed GH-PRL pituitary adenoma can be made according to the results examination of serum endocrine, pathology and clinical manifestations. Its endocrine features are related to the invasion extent of the adenoma. The transsphenoidal approach is the preferred treatment for mixed GH-PRL pituitary adenoma.</p>

Expression of galectin-3 in invasive prolactinomas / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the expression of galectin-3 (Gal-3) in prolactinomas.</p><p><b>METHODS</b>Expressions of Gal-3 were evaluated by immunohistochemistry using polyclonal antibody in 16 invasive prolactinomas and 16 prolactinomas.</p><p><b>RESULTS</b>Gal-3 was expressed both in invasive prolactinomas and noninvasive prolactinomas while significantly higher expression seen in the invasive prolactinomas (P < 0.05).</p><p><b>CONCLUSION</b>Gal-3 expression may be used as a useful indicator to determine the invasiveness and prognosis of prolactinomas.</p>