Infant-onset myasthenia gravis, an autoimmune disease specific to Asians predominantly affects neuromuscular junctions in ocular muscles. An AChR alpha peptide (p71-91) specific autoreactive CD4+ alpha beta T cell clone was established by stimulating PBMC from a patient heterozygous for two disease-susceptible HLA-DR9-DQ9 and DR13-DQ6 haplotypes with a mixture of overlapping peptides covering AChR alpha. The T cell clone recognized the AChR alpha peptide in the context of the HLA-DQ6 molecule and produced a large amount of IFN-gamma and a trace amount of IL-4. A part (p75-83) of the core epitope of the autoantigenic peptide (p75-87) is encoded for by an exon P3A of the AChR alpha gene which can be alternatively spliced. The T cell clone responded to the recombinant AChR alpha protein with a P3A exon product, but not without a P3A exon product. We investigated responses of the T cell clone to 114 analogue peptides carrying single residue substitutions of the core AChR alpha peptide. The majority of analogues substituted at residues Phe-77, Leu-80 and Asn-82 stimulated proliferation of the T cell clone. Conversely, the majority of analogue peptides substituted at either Gln-81 or Glu-83 did not stimulate proliferative responses, and all exhibited strong or intermediate inhibitory effects on proliferative responses of the T cell clone to the wild type peptide, possibly by TCR antagonism. Thus, an HLA class II allele specific to Asians may directly control susceptibility to the Asian-specific type of myasthenia gravis. Analogues of the auto-antigenic AChR alpha peptide may prove effective for new immunosuppressive therapy.

Antibodies, Blocking↗

PubMedDate not supplied

Surgical treatment of advanced gastric cancer with metastasis in para-aortic lymph node.

We have studied the incidence and prognosis of N4 node (para-aortic lymph node) metastases in gastric cancer in 434 patients who had been referred to our department for surgical treatment during the period between 1978 and 1988. N4 nodal involvement was found in 76 (17.5%) of 434 patients who had received a laparotomy with resection, and in 42 (10.5%) of 400 patients who had "curative" resection. When the surgeon assessed that the patients had metastasis in para-aortic lymph nodes, the para-aortic lymph nodes lying above and below the left renal vein were completely removed (R4 gastrectomy). During this period, 42 patients with N4 nodal involvement underwent "curative" resection by R4 gastrectomy. Their treatment results were compared with those of 32 patients who underwent subtotal or total gastrectomy (R2 or R3 gastrectomy) without resection of metastases of para-aortic lymph nodes ("palliative" resection). The operating time and the operative mortality rate were similar in both groups (R4 vs R2 or R3 gastrectomy). The patients who had undergone "curative" resection (R4 gastrectomy) had a significantly higher five-year survival rate than those who had received "palliative" resection. The R4 gastrectomy is a rational and useful surgical procedure for treating patients with N4 nodal involvement.

Carcinoma↗

PubMedDate not supplied

Impact of neck dissection on survival in well-differentiated thyroid cancer: a multivariate analysis of 218 cases.

The management of cervical lymph node metastases in well-differentiated carcinoma of the thyroid has been highly controversial. In the Department of Surgery (II), Kanazawa University Hospital, the surgical management of cervical lymph node metastases in curable well-differentiated carcinoma of the thyroid has been changed from a conservative approach to an aggressive one since 1973. In order to determine whether an aggressive approach for cervical lymph node metastases is adequate, a retrospective multivariate analysis was carried out of 218 cases of well-differentiated thyroid cancer. The patients have been followed up from 5 to 30 years. Multivariate analysis was conducted following Cox's model. As for the results, the aggressive management of cervical lymph node metastases appeared to have an impact on survival. Furthermore, age and sex were confirmed to be important prognostic factors and a partial lobectomy was confirmed to be inadequate as a type of thyroidectomy.

Adenocarcinoma↗