Effects of phenytoin on cell-mediated immunity

Phenytoin is a highly effective anticonvulsant agent that is widely administrated to prevent some kinds of patients with brain tumor. But it has been said that phenytoin may have some immunosuppresive potential for hosts. In this study, we evaluated the effects of phenytoin upon cellular immunity such as NK, CTL and LAK activity in murine models. Fresh splenocytes were taken out from mice (CBA/J, C 3 H/HeN, C 57 BL/6) into which phenytoin had been injected intraperitoneally at a daily dose of 1,000 micrograms for 28 days. The serum concentration of phenytoin in the experimental models was 10-20 micrograms/ml. The cytotoxic activities were estimated by a 4-hr 51Cr release assay. The mitogen-stimulated lymphocyte function was evaluated by 3H-thymidine incorporation into DNA. The NK activity was estimated by cytotoxicity of splenocytes of CBA/J mice against NK-sensitive YAC-1 cells. The cytotoxic T-lymphocyte (CTL) activity was estimated by cytotoxicity of splenocytes of C 57 BL/6 mice which were stimulated in vitro for 5 days by splenocytes of C 3H/HeN treated with mitomycin C, against RSV-M glioma cells. Lymphokine-activated killer (LAK) activity was estimated by cytotoxicity of LAK cells, which were induced from splenocytes of C 3 H/HeN mice by human recombinant interleukin-2 (rIL-2), against syngeneic RSV glioma and allogeneic 203 glioma cells. 3H-thymidine incorporation of splenocytes of C 57 BL/6 mice was reduced significantly (p less than 0.01) in phenytoin-treated mice. The cytotoxicity of splenocytes of non-treated CBA/J mice against YAC-1 cells was 75%, but that of phenytoin-treated CBL/J mice was a few %.(ABSTRACT TRUNCATED AT 250 WORDS)     

Experimental study on the pathogenesis of acute ulceration in obstructive jaundice--with reference to gastric mucosal blood flow

We prepared obstructive jaundice models in rats in order to study the mechanism of acute ulceration in obstructive jaundice centering on impediments to gastric wall blood flow and changes in gastric mucosal NA and PGE2 when the rats were subjected to water immersion restraint stress. The results were: In the obstructive jaundice 2 weeks group, when subjected to water immersion restraint stress, gastric mucosal NA reached a dried up stage from the incipient stage, causing gastric mucosal impediments at the same time, showing a significant decrease of gastric mucosal PGE2. Intragastric pH was at a similar level of excessive acidity in all groups; gastric acid is believed to be a secondary factor promoting ulceration. Gastric mucosal PGE2 showed a significant decrease coinciding with the increase in ulceration index, being a possible factor of ulceration; it is also presumed to regulate gastric wall blood flow alternatively with gastric mucosal NA. Pre-treatment with PGE2 prior to loading stress resulted in a decrease in gastric wall blood flow being significantly controlled. The administration of PGE2 brought about an improvement in gastric wall blood flow and a consequent increase in gastric mucosal NA, being judged effective for acute ulceration in obstructive jaundice.     

LONG‐TERM OUTCOME OF ENDOSCOPIC BALLOON DILATION IN OBSTRUCTIVE GASTROINTESTINAL CROHN's DISEASE

Background: Gastrointestinal strictures are the most often and serious complication in Crohn's disease. Because of the frequent postoperative recurrence in Crohn's disease, endoscopic therapy of gastrointestinal stricture is one of the best therapeutic options. Method: The present study sets out the results from a prospective study of endoscopic dilation therapy on 48 Crohn's disease patients with severe gastrointestinal stenoses. All patients who could not undergo endoscopic balloon dilation therapy (EBD) were operated on. Results: Long‐term success was attained in 32 of the 48 patients; cumulative avoidance of surgery after EBD was 86% at one year and 71% at three. Second, the most hazardous factor was recurrent inflammation causing restenosis. Patients who had strictures with oral luminal dilatation and patients with frequent recurrence had a tendency to be operated on. As a complication, perforation occurred in two cases (3.3%). Conclusions: EBD therapy for Crohn's stricture in the gastrointestinal tract is recommended before surgical intervention.     

Bipolar prosthetic replacement for the treatment of avascular necrosis of the femoral head.

Eighty-three hips in 66 patients with nontraumatic avascular necrosis of the femoral head (ANFH) showing evidence of severe collapse or secondary osteoarthritic changes were treated with surgical implantation of bipolar hip prostheses either with or without cement fixation of femoral stems. The cases were observed for more than three years (range, three to ten years seven months; average, five years seven months) and assessed in terms of functional and roentgenographic results. These data were compared with the results of classic hemiarthroplasties using fixed head prostheses (Austin-Moore-type with curved or straight stem) that were performed at the authors' institutions before 1980. The results confirm that the clinical outcome is improved with use of the bipolar prosthesis. Satisfactory results (a score of 80 or greater on a hip function scoring system proposed by the Japanese Orthopaedic Association) were maintained throughout the follow-up period in most cases (71 of 83 hips) with the bipolar prosthetic replacements. In a group of patients with unsatisfactory results (12 hips), proximal migration of prosthetic head was seen in two cases. The incidence of proximal migration of bipolar heads, including those exhibiting minimal movement, was significantly lower when compared with that observed in an Austin-Moore-type head-fixed prosthesis group (7/83 versus 12/19) during a comparable postoperative follow-up period. It is noteworthy that the proximal migration of the bipolar head was not progressive, and, in most cases observed more than five years, the cartilaginous spaces of acetabulum were preserved, whereas in the Austin-Moore-replaced group, the migration was evident and progression occurred within three years of surgery.(ABSTRACT TRUNCATED AT 250 WORDS)     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.     

Effects of diet with or without exercise on leptin and anticoagulation proteins levels in obesity.

Obesity is a risk factor for cardiovascular disease and thromboembolic events. We investigated the effects of weight reduction by a 12-week calorie-restricted diet with or without aerobic exercise (diet group and diet plus exercise group) on leptin and anticoagulation proteins levels. Forty-two obese nondiabetic individuals were evaluated for blood levels of leptin, protein C activity, free protein S antigen and for body fat area calculated on computerized tomography before and after intervention. Before intervention, serum levels of leptin and free protein S antigen correlated positively with several adiposity-related parameters. After the program, body weight and fat area were significantly decreased in both groups. Body mass index and leptin levels decreased in both groups, with a larger change in the diet plus exercise group than in the diet group. Although protein C activity levels did not change in both groups, free protein S antigen levels decreased significantly in the diet plus exercise group. In conclusion, the 12-week programs had significant effects on the initial weight reduction and body fat mass, decreasing lepin levels in obese nondiabetic individuals. To clarify whether aerobic exercise has additional or direct effects on the anticoagulation system, a study in a large number of individuals is needed.     

Schizotypal disorder and schizophrenia: a profile analysis of neuropsychological functioning in Japanese patients.

This study compares neuropsychological functioning in a Japanese schizophrenia spectrum disorder group and a group of healthy Japanese volunteers. Participants were 37 patients diagnosed with schizophrenia, 28 schizotypal patients, and 99 psychiatrically-normal volunteers. A wide range of cognitive measures were examined. All participants completed a Japanese version of a neuropsychological battery assessing executive function, working memory, processing speed, language, verbal memory, and spatial organization. Comparisons of neuropsychological function demonstrated similarities and differences between patients diagnosed with schizotypal disorder and those diagnosed with schizophrenia. Impairments in verbal memory, language, and processing speed were common to both patient groups and may represent a vulnerability to schizophrenia. Impairments in aspects of working memory, spatial organization and executive function were preferentially observed in schizophrenia and may be features of the overt manifestation of psychosis. Possible differences in the contributions of prefrontal and temporo-limbic structures provide direction for further studies.     

Mirror foot: treatment of three cases and review of the literature

Purpose  To describe three cases of mirror foot and to develop a new classification of the mirror feet with an emphasis on their treatment. Methods  Surgical treatment was performed on three patients with mirror foot. Mirror feet in the English literature were surveyed and cases found in PubMed as well as our three cases were classified according to a new classification that was an analogy of the mirror hand classification proposed by Al-Qattan et al. (J Hand Surg Br 23:534–536, 1998). Results  All three cases obtained satisfactory outcome after the treatment. In addition to these cases, 28 mirror feet were well described in the English literature, among which only seven cases have been documented for their treatment. All of the cases could be assigned to one of the categories of the proposed classification. Conclusion  Mirror foot is a very rare congenital deformity of the foot. We successfully treated three novel cases of mirror feet. A classification of the mirror feet proposed in this article was useful in order to understand its nature and obtain a guideline for its treatment.