Guillain-Barre syndrome with meningoencephalitis after Campylobacter jejuni infection

A 14-year-old boy presented with progressive ascending muscle weakness, urinary retention and disturbed consciousness. Initially his cerebrospinal fluid showed pleocytosis, and protein-cellular dissociation developed later. Campylobacter jejuni was isolated from his stool and serum anti-ganglioside antibodies were positive. Our case suggests that coexistence of meningoencephalitis at an early stage of illness does not necessarily exclude the diagnosis of Guillain-Barre syndrome.     

Phase II study of irinotecan combined with mitomycin-C for advanced or recurrent squamous cell carcinoma of the uterine cervix: the JGOG study

OBJECTIVES: The efficacy and toxicity of combined therapy with irinotecan (CPT-11) plus mitomycin-C (MMC) were evaluated in patients with advanced or recurrent squamous cell carcinoma (SCC) of the uterine cervix. METHODS: CPT-11 (100 mg/m(2)) was administered on days 1, 8, and 15 by intravenous (iv) infusion over 90 min, while MMC (10 mg/m(2) iv) was given on day 1. This regimen was repeated every 28 days and at least two courses were given. RESULTS: Among 51 eligible patients (median age: 52 years; range: 25-72 years), 2 showed complete response (CR) and 24 showed PR, for an overall response rate (ORR) of 51.0% (95% confidence interval: 36.6-65.3%). In patients without prior chemotherapy, the ORR was 54.8% (38.7-70.2%). Twenty-five patients (Ib2:3, IIb:17, and IIIb:5) received this regimen as neoadjuvant chemotherapy and their ORR was 76% (54.9-90.6%). Twenty-two patients were able to undergo radical surgery after NAC. The major toxicity was neutropenia, which was grade 3-4 in 59% of the patients. Grade 3-4 thrombocytopenia and anemia were also seen in 26% of the patients each. The most common nonhematologic toxicity was diarrhea (grade 3-4 in 12%). CONCLUSION: CPT-11 combined with MMC can be effective against advanced or recurrent SCC of the uterine cervix.     

Preoperative assessment of the depth of early gastric cancer invasion by transabdominal ultrasound sonography (TUS): a comparison with endoscopic ultrasound sonography (EUS)

BACKGROUND/AIMS: Transabdominal ultrasound sonography (TUS) is considered a useful diagnostic tool ascertaining depth of cancer invasion, but there are few detailed studies on its accuracy in preoperative estimations of depth of invasion in early gastric cancer (mucosal and submucosal cancer). We retrospectively analyzed the clinical efficacy of preoperative evaluation by TUS in early gastric cancer in comparison with endoscopic ultrasound sonography (EUS). METHODOLOGY: A total of 101 patients preoperatively diagnosed as early gastric cancer were enrolled in the current study. Patients were given 300cc of water subsequent to administration of an anti-peristaltic agent to facilitate filling the gastric lesion with water and TUS was performed. All patients were preoperatively examined by both EUS and TUS. RESULTS: The depth accuracy in mucosal cancer was 59% with EUS and 66% with TUS. When submucosal cancers were subdivided into shallow and deep submucosal cancers, the depth of mucosal and shallow-submucosal (SM1) cancers were correctly assessed 80% and 78% by EUS and TUS, respectively. Accuracy increased by 12% in mucosal cancer by combining EUS and TUS diagnoses. CONCLUSIONS: The diagnostic value of TUS is comparable to that of EUS in assessing depth of invasion of early gastric cancer, however, TUS had a possibility of misdiagnosing the depth of tumors located at the anterior wall. To ensure an accurate estimation of the depth of tumor invasion, it is recommended that TUS and EUS be done simultaneously.     

Tissue engineering using magnetite nanoparticles and magnetic force: heterotypic layers of cocultured hepatocytes and endothelial cells

Novel technologies to establish three-dimensional, in vivo-like tissue consisting of various types of cells are required for tissue engineering. We applied magnetic force to construct a heterotypic, layered coculture system of rat hepatocytes and human aortic endothelial cells (HAECs) that was not limited by cell type. Magnetite cationic liposomes carrying a positive surface charge to improve adsorption accumulated in HAECs at a concentration of 38 pg of magnetite per cell. Magnetically labeled HAECs specifically accumulated onto hepatocyte monolayers at sites where a magnet (4000 G) was positioned, and then adhered to form a heterotypic, layered construct with tight and close contact. This cocultured construct significantly (p < 0.05) enhanced albumin secretion by hepatocytes compared with that in homotypic cultures of hepatocytes or heterotypic cocultures of hepatocytes and HAECs without magnets. These results suggest that this novel use of magnetite nanoparticles and magnetic force, which we refer to as "magnetic force-based tissue engineering" (Mag-TE), offers a major advancement in tissue engineering.     

Social stress-induced cortisol elevation acutely impairs social memory in humans

Although stress is known to affect the memory process, little has been elucidated regarding its effect on social memory. In this study, 30 subjects' social memory (face-name association memory) performance was tested. Twenty subjects were exposed to social stress with a subsequent test of social memory, while the remaining ten subjects served as controls. Free cortisol was determined via saliva samples taken before and after the social stress exposure. Because stress hormones might have biphasic actions on neurons, we separated the subjects with cortisol elevations between high and low responders. The high responders had significantly impaired social memory. Furthermore, we observed a negative relation between social stress-induced cortisol elevation and social memory. These results indicate that social stress acutely impairs social memory.     

Spred-2 suppresses aorta-gonad-mesonephros hematopoiesis by inhibiting MAP kinase activation

In midgestation mouse embryos, the aorta-gonad-mesonephros (AGM) region generates hematopoietic stem cells and definitive hematopoiesis is regulated by cell-cell interaction and signaling molecules. We showed that a Ras/mitogen-activated protein (MAP) kinase signaling-specific inhibitor and a dominant negative mutant Ras blocked the production of CD45+ hematopoietic cells in embryonic day 11.5 AGM culture, indicating an essential role for the MAP kinase pathway in AGM hematopoiesis. Overexpression of the Ras/MAP kinase pathway regulator, Spred-2, in the AGM culture significantly reduced the number of CD45+ cells. In contrast, production of CD45+ cells from the AGM region of Spred-2-null mice was up-regulated as compared with wild-type littermates. Furthermore, Spred-2-deficient mice exhibited elevated hematopoietic colony formation from vascular endothelial-cadherin+ cells. These data indicate that Spred-2 functions as a negative regulator of AGM hematopoiesis by inhibiting hematopoietic cytokine signaling.     

Altered agonist sensitivity and desensitization of neuronal mGluR1 responses in knock-in mice by a single amino acid substitution at the PKC phosphorylation site

mGluR1 and mGluR5 of the metabotropic glutamate receptor family are coupled to inositol trisphosphate-Ca2+ signal cascades and evoke distinct Ca2+ responses in neural cells and heterologously expressing cells. In heterologous cells, stimulation of recombinant mGluR1 evokes a single-peaked Ca2+ response whereas mGluR5 elicits an oscillatory Ca2+ response. The distinct Ca2+ responses are interchangeable by single amino substitution of aspartate for threonine at the corresponding position of the carboxy-terminal cytoplasmic regions of mGluR1 and mGluR5, respectively. In this investigation, we generated knock-in mice, termed mGluR1 D854T mice, in which aspartate of mGluR1 was replaced with threonine. We examined the effect of this D854T substitution on Ca2+ and current responses mediated by mGluR1 in cultured cerebellar Purkinje cells. Stimulation of mGluR1 D854T by a group 1 mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG) evoked, as in wild-type mGluR1, only single-peaked Ca2+ responses as measured by Ca2+ fluorometric analysis. We then examined mGluR1-induced inward currents carried by nonselective cation channels during whole-cell recordings from cultured Purkinje cells. The mGluR1 D854T mutation abolished the responsiveness of mGluR1 to low concentrations of DHPG (0.5-500 nM) and reduced its desensitization during prolonged agonist application. mGluR1 D854T homozygous mutants showed no apparent behavioural abnormality as analysed by motor movement tests. These results indicate that, although additional modulatory mechanisms seem to be required to produce oscillatory Ca2+ responses of mGluR1, the single amino acid substitution at position 854 of mGluR1 is capable of influencing the kinetics of neuronal mGluR1 responses, most probably through PKC-mediated phosphorylation.     

Alpha-1 antitrypsin deficiency with severe pulmonary emphysema

Alpha-1 antitrypsin (AAT) deficiency is a hereditary disorder characterized by an early onset of emphysema. While this disease is common in the Caucasian population, it is quite rare in Japan. To date, only 15 traits have been reported and it can be speculated that many cases of this genetic deficiency may have been overlooked. We report an additional case of AAT deficiency with severe emphysema that is genetically determined as S(iiyama) variant by allele-specific polymerase chain reaction (PCR) analysis.