N-methyl-D-aspartate exposure blocks glutamate toxicity in cultured cerebellar granule cells.

Exposure of cultured cerebellar granule cells to glutamate results in a concentration-dependent (EC50 = 22.7 +/- 0.4 microM) and delayed (24-72 hr) neurotoxicity, which is blocked by the specific N-methyl-D-aspartate (NMDA) receptor antagonists 2-amino-5-phosphovalerate and MK-801 but is unaffected by the non-NMDA receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione and 6,7-dinitroquinoxaline-2,3-dione. Although glutamate toxicity in these cells is mediated by the NMDA subtype of glutamate receptor, pretreatment of cerebellar granule cells with subtoxic concentrations of NMDA markedly antagonizes the neurotoxic actions of glutamate, with an IC50 of 55 +/- 4 microM. The neuroprotective effect of NMDA requires a preincubation time of approximately 120 min to be fully manifested and does not require the presence of NMDA during glutamate exposure. These data demonstrate that NMDA receptors mediate both neurotoxicity and neuroprotection in cerebellar granule cells. Among four glutamate receptor agonists tested (NMDA, quisqualate, ibotenate, and kainate), only NMDA was able to provide a robust neuroprotection against glutamate toxicity. Quisqualate was neither neurotoxic nor neuroprotective, whereas ibotenate, which was nontoxic by itself, induced a small degree of neuroprotection. In contrast, kainate, which was neurotoxic to cerebellar granule cells, also provided considerable neuroprotection against glutamate toxicity. Because preincubation of cerebellar granule cells with NMDA fails to alter NMDA receptor-mediated phosphoinositide hydrolysis or the specific binding of [3H]MK-801 to NMDA receptors, it appears that the neuroprotective effects of NMDA are not due to NMDA receptor desensitization.     

Further evidence supporting a cause and effect relationship between blood transfusion and earlier cancer recurrence.

Studies of associations between perioperative blood transfusions and later recurrence of solid tumors have yielded conflicting results. A previous analysis of transfused patients suggested that recurrence was associated with transfusion of whole blood as opposed to red blood cell concentrates. Additional analyses were performed on patients with cancers of the colon, rectum, cervix, and prostate to determine if patients receiving whole blood, red blood cells only, or no transfusions had differing outcomes. Patients receiving 1 unit or more of whole blood had uniformly poor outcomes compared with nontransfused patients (p less than 0.001). In contrast, patients receiving only red blood cells had progressively worse recurrence and death rates with increasing numbers of transfusion, suggesting the presence of a dose-effect relationship. Employing multivariate techniques, blood transfusion of less than or equal to 3 units that included any whole blood were independently and significantly associated with earlier recurrence (p = 0.003) and death due to cancer (p = 0.02). Transfusions of less than or equal to 3 units of blood comprised solely of red blood cell concentrates were associated with no greater risk of recurrence than that seen in patients receiving no transfusion (p = 0.50). These results provide a potential explanation for the disparate results reported in studies of blood transfusion and cancer outcome. The marked difference in outcome seen between patients receiving a few units of red blood cells and comparable patients receiving even one unit of whole blood are consistent with the hypothesis that transfusion of stored blood plasma causes earlier tumor recurrence in some instances. Strategies for reducing these risks might include avoidance of whole blood transfusions when only 1-3 units are required, more conservative transfusion practice, use of autologous blood transfusions, and perhaps, use of red blood cells washed free of plasma and white cell debris. Clinical trials to test these hypotheses are urgently needed.     

Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insulinoma cells.

Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non-insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells. In addition, glucose-induced insulin secretion is inhibited by IAPP. We studied the effect of IAPP on proinsulin biosynthesis in rat insulinoma (RINr) cells. Glucose at concentrations of 0, 15, 30, 60, 100, and 300 mg/dl stimulated proinsulin biosynthesis in a dose-responsive and and actino-mycin D-inhibitable manner after 6 h of incubation. At a glucose concentration of 300 mg/dl, IAPP decreased the mean responses of proinsulin biosynthesis to 61.2 and 29% at concentrations of 0.1 and 1 microM, respectively, compared with the IAPP-free control. In conclusion, IAPP inhibits glucose-induced proinsulin biosynthesis in RINr cells. IAPP might play an important role in the pathogenesis of type 2 diabetes mellitus.     

Prognostic significance of caspase-3 expression in primary resected esophageal squamous cell carcinoma.

AIMS: The present study retrospectively examines the expression of caspase-3 in primary resected esophageal squamous cell carcinoma (ESCC) and the correlation between the outcome of patients and the expression of proteins. METHODS: Immunohistochemistry and Western blot analyses were used to analyse the expression of caspase-3 in 40 archival specimens of patients with primary resected ESCC. RESULTS: According to our cut-off point of the staining for caspase-3, 24 (60%) cases were positive and 16 (40%) negative. Caspase-3 expression correlated with a significant favorable prognosis in primary resected ESCC (P=0.02). A multivariate analysis of clinical and biological factors indicated that stage, tumor differentiation, and caspase-3 expression were independent prognostic factors. CONCLUSIONS: Caspase-3 expression might be a good and new prognostic indicator for primary resected ESCC.     

Immunohistochemical analyses of gastric stromal tumors in Taiwanese.

BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs), identified by the presence of CD117 (KIT), were previously classified as gastric and intestinal smooth muscle tumors prior to the availability of immunohistochemical methods. This study evaluated the percentage of GISTs previously diagnosed as gastric smooth muscle tumors in our hospital during an 11-year period. METHODS: A total of 81 surgically resected gastric smooth muscle tumor specimens from 81 patients were collected from January 1986 to December 1997. Immunohistochemical studies were performed on these tumors with antibodies of CD34, CD117, smooth muscle actin (SMA), S-100, and desmin. RESULTS: Among the 81 tumors, 74 (91.4%) were CD117-positive and were classified as GISTs. Among the 74 GISTs, CD34 was positive in 72 tumors (97.3%), SMA was positive in 12 tumors (16.2%), desmin was positive in 5 tumors (6.7%), and S-100 was positive in 4 tumors (5.4%). The 7 tumors classified as non-GISTs had the following immunohistochemical characteristics: 1 was a CD117-negative CD34-positive stromal tumor (GINST) [1/81, 1.2%]; 3 were schwannomas with strong S-100-positive characteristics (3/81, 3.7%); and 3 were smooth muscle tumors with both SMA- and desmin-positive status (3/81, 3.7%). No clear relationship between CD117 or CD34 expression and prognosis was found for these tumors. CONCLUSIONS: The majority (91.4%) of gastric tumors originally diagnosed as gastric smooth muscle tumors were GISTs, except for small groups of smooth muscle tumors and schwannomas.     

模拟病例教学方法在儿科护理学教学中的应用

在儿科护理学教学中采用模拟病例教学方法,旨在探寻提高儿科护理学实习质量的新途径.在儿科护理学教学中,将学生分为对照组和实验组,从理论授课阶段、见习阶段和实习阶段逐步实施模拟病例教学方法,并对教学效果进行了讨论和评价.     

Clinic experience of peridual administration with 0.975% bupivacaine

Two hundred patients were given peridural anaesthesia with 16 ml of 0.975% plain bupivacaine in connection with operations on the lower extremities, and the lower abdomen or perineum. More than 92% of these had a good anaesthesia and a pronounced motor block. The frequency of serious complications was low but when they existed they were usually due to the spread of the anaesthesia which led to circulatory and respiratory insufficiency. It is therefore essential to be able to recognize such complications early and treat them rapidly.     

Tooth-brushing epilepsy with ictal orgasms.

We report a 41-year-old woman with complex reflex epilepsy in which seizures were induced exclusively by the act of tooth brushing. All the attacks occurred with a specific sensation of sexual arousal and orgasm-like euphoria that were followed by a period of impairment of consciousness. Ictal EEG demonstrated two events of epileptic seizure that were provoked after tooth brushing for 38 and 14 seconds, respectively. The interictal EEG showed epileptiform discharges over the right anterior temporal region and interictal single photon emission computed tomography (SPECT) scan showed relative hypoperfusion in the uncus of right temporal lobe. Brain magnetic resonance imaging (MRI) revealed right hippocampal atrophy. We suggest that tooth-brushing epilepsy, especially with sexual ictal manifestations, may provide insight into the cerebral pathophysiology at the right temporolimbic structure.     

Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity

Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (> or =27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m(2) in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.