Vaccination with a MHC class II peptide in Alum and inactive pertussis strongly ameliorates clinical MG in C57BL/6 mice

We have investigated the efficacy of immunization against peptides from predisposing MHC class II molecules in human-compatible adjuvants for ameliorating experimental autoimmune myasthenia gravis (EAMG). C57BL/6 mice were immunized three times with the peptide I-Abetab62-76 in Alum+killed pertussis organisms (PT) prior to two injections with tAChR. The treatment greatly reduced the occurrence and severity of clinical MG relative to controls that received saline/Alum+PT or none. It also reduced antibody and T-cell responses against tAChR. The results have important implications for the possible immunotherapy of MG by targeting disease-associated MHC.     

Ganglioside complexes as new target antigens in Guillain-Barré syndrome

Antibodies specific for a complex of gangliosides GD1a and GD1b (GD1a/GD1b) were found in sera from eight of 100 patients with Guillain-Barre syndrome (GBS) by the use of enzyme-linked immunosorbent assay and thin-layer chromatogram immunostaining. Those sera also had antibody activities to such ganglioside complexes as GD1a/GM1, GD1b/GT1b, and GM1/GT1b but had little or no reactivity to the each isolated antigen. Clustered epitopes of the ganglioside complex in the plasma membrane may be targeted by such an antibody, and interaction between the antibody and ganglioside complex may induce the neuropathy.     

p53 Gene Mutations in Human Prostate Cancers in Japan: Different Mutation Spectra between Japan and Western Countries

The involvement of p53 mutations in prostate cancers in Japan was investigated. To evaluate any possible clinicopathological significance, p53 mutations in 40 samples from 36 Japanese prostate cancers of different stages (five cases of latent tumors, three of stage A cancers, 10 of stage B, five of stage C and 13 of stage D), including four lymph node metastases of stage D cases, were examined by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and sequencing. Mutations were detected in five of 40 samples (12.5%); four were in primary cancers and the other in a lymph node metastasis from one of them. All mutation-positive cases were in stage D, and the mutation frequency in stage D cases was 31%. This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans. However, a difference was noted between Japanese and Americans in the p53 mutational spectrum (at CpG site), presumably arising from variation in the underlying etiotogic factors.     

Radiation therapy for small-cell lung cancer: results of the 1995-1997 patterns of care process survey in Japan

The Patterns of Care Study (PCS) conducted a nationwide audit survey in order to establish the national practice process of radiation therapy for small-cell lung cancer (SCLC) and examined the influence of institutional stratification on the process of care in Japan. The PCS randomly sampled institutions and patients using a two-stage cluster method and surveyed the process of radiation therapy for 174 stage I-III SCLC patients according to the category of institution, stratified as follows: A1, academic institutions treating > or = 300 patients a year; A2, <300 patients; B1, non-academic institutions treating > or = 120 patients a year; and B2, <120 patients. Karnofsky performance status distributions showed significant variance by stratification of institutions (P=0.013). Patients treated on an outpatient basis accounted for 32% in A1, 23% in A2, 8% in B1, but only 5% in B2 (P=0.007). A photon energy > or = 10 MV was used for 87% of patients in A1, 69% in A2, 54% in B1 and 23% in B2 (P=0.001). Contralateral hilus was irradiated for 11% of patients in A1, 17% in A2, 29% in B1 and 3% in B2 (P=0.001). Field size reduction during the treatment course was done for 77% of patients in A1, 54% in A2, 60% in B1 and 42% in B2 (P=0.007). Ninety-two percent of patients received combined chemotherapy and radiation therapy, and the most frequently used drugs were etoposide (91%) and cisplatin (69%). The results of clinical studies on SCLC had favorably penetrated into the clinical practice. However, the stratification of institutions significantly affected the process of radiation therapy in Japan.     

Non-small cell lung cancer (NSCLC)

The goal of radiation therapy for non-small cell lung cancer (NSCLC) is to improve the survival rate of patients without increasing treatment-related toxicity and to improve patients' quality of life. Several prospective randomized trials have demonstrated a survival advantage in combined modality treatment over radiotherapy or chemotherapy alone when a cisplatin-based chemotherapy regimen is utilized in the treatment plan. Combined modality treatment of cisplatin-based chemotherapy and radiotherapy is standard treatment for selected patients such as those with better performance status with locally or regionally advanced lung cancer including T3-T4 or N2-N3. Determining the contribution of new agents in combined modality treatment will require carefully designed and conducted clinical trials. High-dose involved field radiation therapy using 3D-conformal radiation therapy potentially enables the use of higher doses than standard radiation therapy, because less normal tissue is irradiated, and may improve local control and survival. The combination of radiotherapy with chemotherapy and dose escalation using 3D-conformal radiation therapy is also a possibility in unresectable NSCLC. In surgery cases, the results of several Phase III trials of cisplatin-based preoperative chemotherapy have suggested survival improvement. But the concept needs to be tested in a larger Phase III trial.     

Protein phosphatase 2Aα involvement in granulocytic differentiation of HL-60 cells

Protein phosphatase 2Aα (PP-2Aα) is one of the catalytic subunits of PP-2A, which is composed of catalytic and regulatory subunits. In fission yeasts, PP-2A mutants cause mitotic defects and strikingly different cell cycle phenotypes. In rat hepatocellular carcinomas, mRNA expression of PP-2Aα was increased compared to that of normal hepatocytes. From these studies, PP-2Aα has been thought to be involved in proliferation, and we expected that PP-2Aα would decrease in HL-60 cells on dimethyl sulfoxide(DMSO)-induced granulocytic differentiation with decreased growth rate. In this study, we show that PP-2Aα expression increases in HL-60 cells on DMSO-induced granulocytic differentiation, while PP-1γ, which is one of catalytic subunits of protein phosphatase 1, expression did not change significantly. These results suggest that PP-2Aα may be involved in regulation of differentiation of hematopoietic cells.     

Anesthetic management of tracheobronchial stent insertion in patients who underwent laser resection, balloon dilatation and tracheostomy in advance

BACKGROUND: We report successful management of tracheobronchial stent insertion under general anesthesia. METHODS: In thirty-two cases, tracheobronchial stent insertion was performed under general anesthesia. The technique for airway management was chosen depending on the type of stent or the constriction level of the airway portion. We employed tracheostomy in order to avoid repeated intubations during the insertion of Dumon or Dynamic stent. In case of severe airway stenosis, laser resection or balloon dilatation was performed before stent insertion. RESULTS: We had 32 successful cases in 36 trials. Four trials failed due to insufficient expansion in one, mismatches of stent angle in one and pneumomediastinum in one. There was no exacerbation of respiratory condition in failed cases. There was no case who needed percutaneous cardiopulmonary support system. CONCLUSIONS: We managed tracheobronchial stent insertion under general anesthesia. Both the airway expansion by laser resection or balloon dilatation before stent insertion and also the insertion of Dumon or Dynamic stent through a tracheostomy were helpful strategies. These techniques facilitated more definitive airway maintenance and stable anesthetic management.