Growth effect of gastrin on gastric cancer and its clinical implications for gastric cancer surgery

This study was aimed at investigating the effect of gastrin on the growth of gastric cancer and evaluating postoperative hypergastrinemia in patients that had received various types of gastrectomy for gastric cancer. RT-PCR for gastrin/CCKB receptor mRNA was performed in human gastric cancer cell lines and tissue. The effect of gastrin or glycine-extended gastrin on the growth of gastric cancer cell lines was determined by MTT assay. Serum gastrin levels were compared with respect to the resection type of gastric cancer surgery. Gastrin/CCKB receptor mRNA expression was detected in all 9 gastric cancer cell lines, and in 19 of 29 (62%) gastric cancer tissue samples. Growth of gastric cancer cell lines containing the gastrin/CCKB receptor was significantly enhanced by gastrin and glycine-extended gastrin. The proximal gastrectomy group had a significantly higher mean serum gastrin level than the distal subtotal gastrectomy, total gastrectomy, or preoperative groups (p<0.05). Our study confirms that a high proportion of gastric cancer tissue samples express the gastrin/CCKB receptor, which can stimulate the growth of gastrin/CCKB receptor-positive gastric cancer cells. In addition, we confirm that hypergastrinemia can be induced in about half of patients after proximal gastrectomy. More studies are needed to clarify the relationship between hypergastrinemia and tumor recurrence after proximal gastrectomy.     

Biodegradation of the Insecticide N,N-Diethyl-m-Toluamide by Fungi: Identification and Toxicity of Metabolites

Fungi (Cunninghamella elegans ATCC 9245, Mucor ramannianus R-56, Aspergillus niger VKMF-1119, and Phanerochaete chrysosporium BKMF-1767) were tested to elucidate the biologic fate of the topical insect repellent N,N-diethyl-m-toluamide (DEET). The elution profile obtained from analysis by high-pressure liquid chromatography equipped with a reverse-phase C-18 column, showed that three peaks occurred after incubation of C. elegans, with which 1 mM DEET was combined as a final concentration. The peaks were not detected in the control experiments with either DEET alone or tested fungus alone. The metabolites produced by C. elegans exhibited a molecular mass of 207 with a fragment ion (m/z) at 135, a molecular mass of 179 with an m/z at 135, and a molecular mass of 163 with an m/z at 119, all of which correspond to N,N-diethyl-m-toluamide-N-oxide, N-ethyl-m-toluamide-N-oxide, and N-ethyl-m-toluamide, respectively. M. ramannianus R-56 also produced N, N-diethyl-m-toluamide-N-oxide and N-ethyl-m-toluamide but did not produce N-ethyl-m-toluamide-N-oxide. For the biologic toxicity test with DEET and its metabolites, the freshwater zooplankton Daphnia magna was used. The biologic sensitivity in decreasing order was DEET > N-ethyl-m-toluamide > N,N-diethyl-m-toluamide-N-oxide. Although DEET and its fungal metabolites showed relatively low mortality compared with other insecticides, the toxicity was increased at longer exposure periods. These are the first reports of the metabolism of DEET by fungi and of the biologic toxicity of DEET and its fungal metabolites to the freshwater zooplankton D. magna.     

Deep brain stimulation in Parkinson disease: a metaanalysis of patient outcomes

OBJECT: Deep brain stimulation (DBS) to treat advanced Parkinson disease (PD) has been focused on one of two anatomical targets: the subthalamic nucleus (STN) and the globus pallidus internus (GPI). Authors of more than 65 articles have reported on bilateral DBS outcomes. With one exception, these studies involved pre- and postintervention comparisons of a single target. Despite the paucity of data directly comparing STN and GPI DBS, many clinicians already consider the STN to be the preferred target site. In this study the authors conducted a metaanalysis of the existing literature on patient outcomes following DBS of the STN and the GPI. METHODS: This metaanalysis includes 31 STN and 14 GPI studies. Motor function improved significantly following stimulation (54% in patients whose STN was targeted and 40% in those whose GPI was stimulated), with effect sizes (ESs) of 2.59 and 2.04, respectively. After controlling for participant and study characteristics, patients who had undergone either STN or GPI DBS experienced comparable improved motor function following surgery (p = 0.094). The performance of activities of daily living improved significantly in patients with either target (40%). Medication requirements were significantly reduced following stimulation of the STN (ES = 1.51) but did not change when the GPI was stimulated (ES = -0.02). CONCLUSIONS: In this analysis the authors highlight the need for uniform, detailed reporting of comprehensive motor and nonmotor DBS outcomes at multiple time points and for a randomized trial of bilateral STN and GPI DBS.     

Aneurysms located at the proximal anterior cerebral artery and anterior communicating artery associated with middle cerebral artery aplasia: case report

BACKGROUND: Aneurysms arising from the proximal anterior cerebral artery (ACA) are quite rare. Here, we report upon such a case of aneurysms located at the proximal ACA and anterior communicating artery associated with middle cerebral artery (MCA) aplasia. CASE DESCRIPTION: A 64-year-old woman complained of severe headache. Brain computed tomography scans demonstrated acute subarachnoid hemorrhage. Angiograms showed 2 aneurysms located at the anterior communicating artery and proximal ACA, but did not show an MCA shadow on the lesion side. Instead, multiple collateral vessels ran toward the sylvian fissure and supplied the MCA territory, together with hypertrophied perforating branches. The operative findings confirmed that the cordlike rudimentary MCA had no internal blood flow. The 2 aneurysms were secured by neck clipping. CONCLUSION: The combined effects of these anomalies on the hemodynamic equilibrium of the arteries and the genesis of the aneurysms are noteworthy.     

Carcinoid tumor arising in a tailgut cyst of the anorectal junction with distant metastasis: a case report and review of the literature

Tailgut cyst is a rare congenital presacral lesion and is believed to arise from the persistent remnants of the postanal gut. Malignancy occurring in a tailgut cyst is extremely rare, and to our knowledge only 5 cases of carcinoid tumor arising in a tailgut cyst have been reported in the literature to date. We report a sixth case of carcinoid tumor arising in a tailgut cyst. The patient was a 41-year-old woman who presented with perianal pain. Sigmoidoscopy showed a 2-cm submucosal mass located 4 cm above the anal verge. The mass was a multilocular cyst with gray-tan solid portions. The cyst was lined by ciliated columnar, squamous, and transitional epithelia with small foci of carcinoid tumor in the cystic wall. The carcinoid tumor showed a trabecular growth pattern with uniform oval or round cells containing fine chromatin and positive immunoreactivity for chromogranin, synaptophysin, and cytokeratin. This case was unique because the tumor occurred at the anorectal junction, not in the retrorectal space, and unlike previously reported cases showed aggressive behavior and distant metastases.     

Pseudobasophilia as an erroneous white blood cell differential count with a discrepancy between automated cell counters: report of two cases

We report two cases that showed erroneous white blood cell differential counts by automated cell counters. Each case showed an interesting discrepancy of differential count between cell counters, and marked pseudobasophilia was observed by one of the two counters. The first patient was a 44-year-old female who suffered from multiple myeloma for more than one and a half years. Increased myeloma cells (43%) in peripheral blood were counted as basophils by the ADVIA 120, and as monocytes by SE-9000, respectively. The second patient was a 72-year-old female diagnosed as having chronic myelomonocytic leukemia. Dysgranulopoietic neutrophils (50%) and monocytes (31%) were increased in the peripheral blood. Dysgranulopoietic neutrophils were counted as basophils by STKS. In contrast, about half of the increased monocytes were counted as neutrophils by the ADVIA 120. These interesting findings highlight the importance of microscopic examination of the blood film in routine laboratory practice, and automated cell counters, especially for the hematologic patients, cannot completely substitute for it. These results also imply that at least some subpopulations with different membrane or cytoplasmic properties may exist even in the similarly classified cells.     

Protection by sustained release of physostigmine and procyclidine of soman poisoning in rats

The efficacy of a combinational prophylactic regimen on the lethality, convulsions, and loss of morphological and functional integrities of the brain induced by an organophosphate soman was investigated in rats. The rats were implanted subcutaneously with osmotic minipumps containing the combinational prophylactic regimen composed of physostigmine, a reversible cholinesterase inhibitor, and procyclidine, an N-methyl-D-aspartate antagonist possessing anticholinergic action, for 3 days, and intoxicated subcutaneously with soman (160 microg/kg, 1.3 LD50). The doses of combinational regimen in minipumps were optimized to achieve 30-35% inhibition of blood cholinesterase activity by physostigmine and 50-100 ng/ml of blood concentrations of procyclidine as clinically available doses, respectively. In comparison, 1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium (HI-6, 125 mg/kg) was administered intraperitoneally 30 min prior to the soman challenge in control groups to reduce mortality of rats without affecting convulsions. Soman induced profound limbic convulsions and 30% mortality, leading to increased blood-brain barrier permeability, neural injuries, learning and memory impairments, and physical incapacitation of survived rats pretreated with HI-6. The combinational regimen, at optimal doses without adverse effects on passive avoidance performances (72 microg/kg/h of physostigmine plus 432 microg/kg/h of procyclidine), exerted full protective effects against lethality, convulsions, blood-brain barrier opening, brain injuries, learning and memory impairments, and physical incapacitation induced by soman. Taken together, it is suggested that the combination of physostigmine and procyclidine, at adequate doses, could be a choice to provide the victims of organophosphate poisoning with chance of intensive care for survival and neuroprotection.     

PKCdelta associates with and is involved in the phosphorylation of RasGRP3 in response to phorbol esters

RasGRP is a family of guanine nucleotide exchange factors that activate small GTPases and contain a C1 domain similar to the one present in protein kinase C (PKC). In this study, we examined the interaction of RasGRP3 and PKC in response to the phorbol ester PMA. In Chinese hamster ovary or LN-229 cells heterologously expressing RasGRP3, phorbol 12-myristate 13-acetate (PMA) induced translocation of RasGRP3 to the perinuclear region and a decrease in the electrophoretic mobility of RasGRP3. The mobility shift was associated with phosphorylation of RasGRP3 on serine residues and seemed to be PKCdelta-dependent because it was blocked by the PKCdelta inhibitor rottlerin as well as by a PKCdelta kinase-dead mutant. Using coimmunoprecipitation, we found that PMA induced the physical association of RasGRP3 with PKCdelta and, using in situ methods, we showed colocalization of PKCdelta and RasGRP3 in the perinuclear region. PKCdelta phosphorylated RasGRP3 in vitro. Previous studies suggest that ectopic expression of RasGRP3 increases activation of Erk1/2. We found that overexpression of either PKCdelta or RasGRP3 increased the activation of Erk1/2 by PMA. In contrast, coexpression of PKCdelta and RasGRP3 yielded a level of phosphorylation of Erk1/2 similar to that of control vector cells. Our results suggest that PKCdelta may act as an upstream kinase associating with and phosphorylating RasGRP3 in response to PMA. The interaction between RasGRP3 and PKCdelta points to the existence of complex cross-talk between various members of the phorbol ester receptors which can have important impact on major signal transduction pathways and cellular processes induced by phorbol esters or DAG