To study the correlation between the spatial cognitive impairment and different subtypes of estrogen receptor α (ERα) of hippocampus in diabetic mice, we used alloxan (intraperitoneal injection) to induce type 1 diabetes in male Kunming mice and compared the spatial cognitive ability of the model mice with that of control mice through Morris water maze test. Meanwhile, using Western blot, we detected the protein expressions of ER-α36, ER-α66, caveolin-1, PKCα, cAMP-response element binding protein 2 (CREB2), and synaptophysin (Syn) in the hippocampus of the mice. The results showed that on the 3rd and 5th days of training, the ability of spatial learning and memory in the diabetic mice was significantly inferior to that of the control mice (P < 0.05). In the diabetic mice, the protein expressions of caveolin-1 and PKCα were decreased (P < 0.05), but ER-α66 expression was unaffected, while ER-α36 and CREB2 expressions were significantly increased (P < 0.05) compared with those of the control mice. The results suggest that abnormal expression of ER-α36 and related signal molecules may be important factors for diabetes-induced spatial cognitive impairment.
Animals ; Caveolin 1 ; metabolism ; Cognitive Dysfunction ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Diabetes Mellitus, Experimental ; physiopathology ; Estrogen Receptor alpha ; metabolism ; Hippocampus ; metabolism ; physiopathology ; Male ; Maze Learning ; Memory ; Mice ; Protein Kinase C-alpha ; metabolism ; Synaptophysin ; metabolism

OBJECTIVETo investigate the association of neuroendocrine differentiation with progression and prognosis of gastric adenocarcinoma.

METHODSClinicopathological data of 240 patients with gastric adenocarcinomas were retrospectively analyzed. The expression of chromogranin A, synaptophysin and secrectagogin in cancer tissue was assessed by immunohistochemistry. The association of neuoroendocrine differentiation parameters with disease progression and survival of patients was analyzed.

RESULTSThe expression of synaptophysin was positively correlated with depth of invasion and secretagogin more often expressed in cases with lymph node metastasis. In Lauren diffuse type of cancer, expression of chromogranin A and secretagogin was unfavorable prognostic predictor. In TNM stage II adenocarcinoma, expression of chromogranin A and synaptophysin related to poor survival, and multivariate Cox proportional hazard model showed that synaptophysin was an independent predictor for poor survival.

CONCLUSIONNeuroendocrine differentiation predicts deeper depth of invasion, more possibility of lymph node metastasis and poor survival in gastric adenocarcinoma.

Adenocarcinoma ; diagnosis ; pathology ; Biomarkers, Tumor ; metabolism ; Chromogranin A ; metabolism ; Disease Progression ; Humans ; Immunohistochemistry ; Lymphatic Metastasis ; Neoplasm Staging ; Neuroendocrine Tumors ; diagnosis ; pathology ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Secretagogins ; metabolism ; Stomach Neoplasms ; diagnosis ; pathology ; Synaptophysin ; metabolism

OBJECTIVETo study the expression of squamous cell markers p63, p40 and CK5/6 in small cell carcinoma of lung (SCLC).

METHODSImmunohistochemical study for squamous cell markers (p63, p40 and CK5/6), neuroendocrine markers (chromogranin A, synaptophysin and CD56) and TTF1 was carried out in 283 cases of SCLC. The diagnostic value of these markers was evaluated.

RESULTSThe expression rate of p63, p40 and CK5/6 were 20.7% (54/261), 7.9% (5/63) and 0.5% (1/221), respectively in the cases of SCLC studied. Amongst the squamous cell markers, CK5/6 had the lowest rate of positivity (P < 0.01). On the other hand, chromogranin A, synaptophysin and CD56 were positive in 61.8% (170/275), 85.5% (242/283) and 89.2% (248/278), respectively. The positivity rate for chromogranin A was lower than that for synaptophysin and CD56 (P < 0.01). TTF1 was expressed in 77.2% (217/281).

CONCLUSIONSp63 and p40 are expressed in a subset of SCLC. In contrast, CK5/6 is rarely positive in SCLC. An immunohistochemical panel of CK5/6, synaptophysin and CD56 is recommended for differential diagnosis of SCLC.

CD56 Antigen ; genetics ; metabolism ; Chromogranin A ; genetics ; metabolism ; DNA-Binding Proteins ; genetics ; metabolism ; Diagnosis, Differential ; Humans ; Keratin-5 ; genetics ; metabolism ; Keratin-6 ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; Small Cell Lung Carcinoma ; genetics ; metabolism ; Synaptophysin ; genetics ; metabolism ; Transcription Factors ; genetics ; metabolism ; Tumor Suppressor Proteins ; genetics ; metabolism

OBJECTIVETo explore the protective effects of rutin against learning and memory impairment induced by trimethyltin (TMT) and investigate the possible mechanism.

METHODSForty 6- to 9-week-old male BALB/c mice were randomized equally into saline group (control), TMT group, TMT+rutin group, and rutin group. Mouse models of learning and memory impairment were establish by acute TMT (2.25 mg/kg) exposure. In TMT+rutin and rutin treatment groups, the mice received intraperitioneal injection of rutin (10 mg/kg) for 1 week before TMT exposure. Twenty-four hours after TMT exposure, Morris water maze test was employed to test the escape latency of the mice, and the synaptophysin expression in the hippocampus and cortex were analyzed by Western blotting.

RESULTSCompared that in TMT group, the escape latency of the mice in water maze test was significantly shorter in the other 3 groups (P<0.05); the escape latency in TMT +rutin group was similar with that in the control and rutin groups (P>0.05). Western blotting showed significantly decreased synaptophysin expression in the hippocampus and cortex in TMT group (P<0.05); synaptophysin expression in TMT +rutin group increased significantly compared with that in TMT group (P<0.05) but showed no statistical significance from that in rutin and control groups (P>0.05).

CONCLUSIONRutin pretreatment offers protective effect against TMT-induced learning and memory impairment in mice possibly by antagonizing decreased synaptophysin in the hippocampus and cortex.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Hippocampus ; drug effects ; metabolism ; Learning ; drug effects ; Male ; Memory Disorders ; chemically induced ; drug therapy ; Mice ; Mice, Inbred BALB C ; Neuroprotective Agents ; pharmacology ; Rutin ; pharmacology ; Synaptophysin ; metabolism ; Trimethyltin Compounds ; adverse effects

OBJECTIVETo explore the mechanisms of acupuncture treatment promoting the motor function recovery of neonate rats with cerebral palsy.

METHODSThe improved hypoxic-ischemic encephalopathy (HIE) means was performed to establish the model of neonate rats with cerebral palsy. All neonate rats were randomly divided into 3 groups: sham group, model group and acupuncture group (n = 20). We observed and scored motor function of rats, measured the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in serum, and also measured the expression of synaptophysin (SYP) and growth associated protein-43 (GAP-43) in the diseased region of cerebral tissue.

RESULTSThe motor function scores (11.3 +/- 0.29) and the serum level of SOD (147.1 +/- 12.7) U/ml in acupuncture treatment group were higher than those of model group ( P < 0.05). The serum level of MDA was lower in acupuncture treatment group than that of model group (P < 0.05). The expression of SYP and GAP-43 in the diseased region of cerebral tissue of acupuncture treatment group were higher than those of model group ( P < 0.05) .

CONCLUSIONAcupuncture-therapy could improve the motor function of neonate rats with cerebral palsy by decreasing the content of MDA in serum, increasing the contents of SOD in serum, and prolonging the upregulation of SYP and GAP-43 expressions in hmin tissue.

Acupuncture Therapy ; Animals ; Animals, Newborn ; Cerebral Palsy ; therapy ; Disease Models, Animal ; GAP-43 Protein ; metabolism ; Hypoxia-Ischemia, Brain ; therapy ; Malondialdehyde ; metabolism ; Rats ; Superoxide Dismutase ; metabolism ; Synaptophysin ; metabolism

OBJECTIVETo investigate the expression of neuron-specific enolase (NSE) and synaptophysin(SYN) proteins in different developmental stages of human embryonic esophagus.

METHODSImmunohistochemistry was used to detect the expressions of NSE and SYN proteins in embryonic esophagus tissues of fetuses of 2, 3 and 4 month gestational age (n=16). One-way ANOVA and LSD-t test were employed to compare the staining intensity and number of positive expression cells in embryonic esophageal tissues of different gestational age.

RESULTSIn fetuses with 2, 3 and 4 months of gestation, the number of NSE-positive nerve cells in the myenteric nerve plexus and submucosa of human embryonic esophageal tissues were 18.38 ± 8.37, 25.00 ± 11.54 and 38.00 ± 15.09, respectively; the staining intensity of NSE-positive nerve cells and nerve fibers in myenteric nerve plexus and submucosa of embryonic esophageal tissues were 74.38 ± 14.93, 62.25 ± 18.59 and 56.44 ± 14.70, respectively. NSE-positive cells were detected in the esophageal epithelium only at the third month. In the fetuses at 2, 3 and 4 months of gestation, SYN in all layers of esophageal tissue were positively or strong positively expressed, especially in the myenteric plexus and submucosal plexus. The staining intensity of SYN-positive cells in embryonic esophagus tissues of 2, 3 and 4 month gestation were 54.69 ± 9.34, 51.84 ± 6.10 and 46.41 ± 6.44, respectively.

CONCLUSIONSYN and NSE may be involved in the regulation of nerve system of esophageal tissues during the human embryonic development.

Esophagus ; embryology ; Female ; Fetus ; Gestational Age ; Humans ; Immunohistochemistry ; Phosphopyruvate Hydratase ; metabolism ; Pregnancy ; Synaptophysin ; metabolism

Gangliocytic paraganglioma (GP) is a rare, benign tumor which is usually found in the duodenum. We here report four recent cases of GP, with successful endoscopic resection in three cases, including a lesion on the ampulla of Vater. In all cases, each lesion had a stalk that facilitated removal using an endoscopic approach. Endoscopic mucosal resection is a feasible and safe treatment if the location, depth, and lymph node status are all favorable and is also helpful for definite diagnosis of unknown duodenal mass. To avoid morbidity resulting from open surgical resection, careful inspection for the peduncle of the GP will help determine the feasibility of endoscopic resection.
Aged ; Ampulla of Vater/pathology ; Chromogranin A/metabolism ; Colonoscopy ; Duodenal Neoplasms/pathology/*surgery ; Endoscopy, Gastrointestinal ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa/pathology/surgery ; Male ; Middle Aged ; Neuroendocrine Tumors/pathology/surgery ; Paraganglioma/pathology/*surgery ; S100 Proteins/metabolism ; Synaptophysin/metabolism ; Tomography, X-Ray Computed

OBJECTIVETo investigate the distribution patterns of neuron-specific enolase (NSE) and synaptophysin (SYN) during the development of human fetal stomach.

METHODSSixteen specimens of human fetal (gestational age 2 to 4 months) gastric tissues were examined with immunohistochemistry for detecting the distribution of NSE and SYN expressions in the gastric walls.

RESULTSDuring the second to fourth gestational months, NSE was strongly expressed in the nerve cells and nerve fibers of the myenteric nerve plexus of human fetal stomach. As the gestational age increased, the numbers of NSE positive cells and fibers increased gradually in the gastric submucosa, but NSE was negative in the gastric mucosa. At the second gestational month, SYN expression was negative in the mucosa but positive in the myenteric nerve plexus; during the third to fourth months, positive SYN expression was found in the mucosa, submucosa and myenteric nerve plexus of the embryonic gastric walls and its expression intensity increased with the gestational age.

CONCLUSIONSYN and NSE are both involved in the regulation of the nervous system in the gastric wall but their expressions and distributions follow different patterns during the development of human fetal stomach.

Fetus ; metabolism ; Gastric Mucosa ; metabolism ; Gestational Age ; Humans ; Immunohistochemistry ; Myenteric Plexus ; Nerve Fibers ; metabolism ; Neurons ; metabolism ; Phosphopyruvate Hydratase ; metabolism ; Stomach ; metabolism ; Synaptophysin ; metabolism

OBJECTIVETo study clinicopathologic features, immunohistochemical profile, diagnosis and differential diagnosis of childhood central nervous system primitive neuroectodermal tumors (CNS PNETs) with the features of ependymoblastoma and neuroblastoma.

METHODSThe clinical data, morphologic and immunohistochemical features were analyzed in 4 cases of pediatric CNS PNETs with features of ependymoblastoma and neuroblastoma. EnVision method immunohistochemistry was applied.

RESULTSFour patients including three boys and one girl presented at the age from 12 month to 4 years and three tumors located in cerebrum, one in brain stem. All tumors showed typical combined histological patterns of ependymoblastoma and neuroblastoma, demonstrating zones of true rosettes, occasional pseudovascular rosettes, and undifferentiated neuroepithelial cells in a prominent background of mature neuropils. There was focal expression of glial fibrillary acidic protein (GFAP) consistent with glial differentiation and epithelial membrane antigen (EMA) consistent with ependymal differentiation. Necrosis was seen in three cases and calcification was present in one case. Immunohistochemically, the rosettes and undifferentiated neuroepithelial cells were positive for vimentin, partially positive for GFAP and EMA but negative for synaptophysin. The tumor cells were also positive for synaptophysin in neuropils. The Ki-67 label index ranged from 20% to 60%.

CONCLUSIONSCNS PNETs with the features of ependymoblastoma and neuroblastoma is a rare tumor with poor prognosis. The tumor primarily occurs in childhood, especially infant and belongs to the family of embryonal tumors of the CNS. The morphologic, immunohistochemical and genetic features are important in differential diagnosis from other tumors of the CNS.

Antigens, Neoplasm ; metabolism ; Central Nervous System ; pathology ; Child ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Immunohistochemistry ; Infant ; Male ; Mucin-1 ; metabolism ; Neuroblastoma ; diagnosis ; pathology ; Neuroectodermal Tumors, Primitive ; diagnosis ; pathology ; Neuroectodermal Tumors, Primitive, Peripheral ; diagnosis ; pathology ; Synaptophysin ; metabolism ; Vimentin ; metabolism

OBJECTIVETo study the clinicopathologic characteristics of parathyroid carcinoma (PTC).

METHODSEleven cases of PTC encountered during the period from 1994 to 2012 were enrolled into the study. Forty cases of parathyroid adenoma (PA) were also retrieved for comparison. The clinical manifestations, laboratory results and pathologic features were analyzed, with literature review.

RESULTSThe main clinical manifestations of PTC included neck mass (11/11), hypercalcemia (11/11) and hyperparathyroidism (11/11). Most patients also had osteoporosis (10/11). In contrast, PA often manifested as hypercalcemia (40/40) and hyperparathyroidism (40/40). Histologic examination of PTC showed that the tumor cells contained clear to eosinophilic cytoplasm and separated by dense bands of fibrosis. The tumor mass was surrounded by thick fibrous capsule. Foci of capsular invasion and vascular permeation were identified at the tumor periphery in all cases. Cellular atypia was not conspicuous but mitotic figures and coagulative necrosis were easily identified. On the other hand, PA were composed of tumor cells with clear to eosinophilic cytoplasm, forming glands, trabeculae or nests. Most of them (35/40) had intact fibrous capsule. Mitotic figures were rarely encountered and tumor necrosis was absent. Immunohistochemical study showed that the tumor cells in PTC were positive for CK19 (11/11), chromogranin A (9/11), synaptophysin (7/11) and parathyroid hormone (11/11). They were negative for thyroglobulin, TTF-1 and calcitonin. The Ki-67 index was less than 10% (range = 2% to 9%). In contrast, the tumor cells in PA were positive (40/40) for CK19, chromogranin A, synaptophysin and parathyroid hormone. They were negative for thyroglobulin, TTF-1 and calcitonin. The Ki-67 index was less than 3%. Follow up-data were available in 9 cases of PTC (duration of follow up = 11 months to 224 months) and 7 of the patients were still alive. Follow up of all PA cases showed no evidence of recurrence.

CONCLUSIONSPTC is a rare malignant endocrine tumor presenting as neck mass. Histologic features suggestive of malignant behavior include presence of coagulative tumor necrosis and capsular/vascular invasion. It needs to be distinguished from other entities such as parathyroid adenoma, papillary thyroid carcinoma and medullary thyroid carcinoma.

Adenoma ; metabolism ; pathology ; Adult ; Carcinoma ; metabolism ; pathology ; Carcinoma, Neuroendocrine ; Carcinoma, Papillary ; Chromogranin A ; metabolism ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hypercalcemia ; etiology ; Hyperparathyroidism ; etiology ; Immunohistochemistry ; Keratin-19 ; metabolism ; Male ; Middle Aged ; Osteoporosis ; etiology ; Parathyroid Hormone ; metabolism ; Parathyroid Neoplasms ; complications ; metabolism ; pathology ; surgery ; Synaptophysin ; metabolism ; Thyroid Neoplasms ; metabolism ; pathology