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Human CD4+ T-cells recognize antigenic peptides in the context of human leukocyte antigen (HLA) class II molecules and produce various lymphokines to proliferate and activate other cells. It was once considered that the T-cell response is an all or nothing type event, but recent studies have clearly indicated that T-cells show many different types of activation in recognition of altered ligands for T-cell receptors (TCR). In this review, we summarize our recent findings on the human CD4+ T-cell response to altered peptide ligands (APL); peptides carrying single residue substitutions in antigenic peptides. We observed the following: 1) TCR antagonism for T-cell clones reactive to non-self or autoantigenic peptides, 2) partial activation (agonism) without cell proliferation, including production of lymphokines and increases in cell size, and in expression levels of several cell surface proteins or survival time in the absence of antigenic stimulus, 3) augmentation in cell proliferation and production of interferon-γ (IFN-γ) and granulocyte monocyte colony stimulating factor (GM-CSF), 4) augmentation of interleukin (IL)-12 production by antigen presenting cell (APC) and the subsequent augmented production of IFN-γ by T-cells. This information provides basic knowledge regarding the characteristics of T-cell recognition of antigens and the subsequent activation, and a novel method for modification of human T-cell responses by altered peptide ligands (APLs), as a possible candidate for antigen-specific immunopotentiating or immunosuppressive therapy against autoimmune diseases, allergies, infectious diseases and malignant tumors.(Internal Medicine 37: 804-817, 1998)

By stimulating peripheral blood mononuclear cells of four healthy donors with a mixture of overlapping peptides representing the core domain of p53, we established two CD4+ alphabeta T cell clones and four lines that recognized wild-type and mutant p53 proteins as well as p53 self peptides in an HLA class II-restricted fashion. Two T cell lines established from two unrelated donors reacted to the p53 peptide (p)153-166 and p108-122, respectively, in the context of DP5 molecules. Two T cell clones established from two other unrelated donors were specific for p193-204 in the context of DRB1*1401 and for p153-165 in the context of DP5, respectively. These two T cell clones responded almost equally to both wild-type and four mutant recombinant p53 proteins. The proliferative responses of these T cell clones to p53 recombinant proteins were augmented by heat denaturing, thereby suggesting that altered conformation of the protein facilitates proteolytic processing to produce antigenic peptides. The DRB1*1401-restricted T cell clone specific for p193-204 killed a B lymphoblastoid cell line homozygous for HLA-DRB1*1401 when the cell line was pre-pulsed with p53 protein as well as peptide. These results indicate that CD4+ T cells reactive to p53 do exist in healthy individuals and the epitopes are probably ignored by the immune system under physiological conditions. It is suggested that such epitopes stimulate T cells to induce anti-p53 antibody production in cancer patients as previously reported by others. The possible involvement of p53-reactive T cells in anti-tumor immunity is discussed.

We investigated binding of p53- and Ras-derived peptides with frequently observed missense mutations, to various L cell transfectants expressing a single species of HLA-DR complex, and found that: (i) all the synthetic peptides bound to various DR complexes with a variable affinity; (ii) some DR allelic products had a high affinity for both p53- and Ras-derived peptides (e.g., DRB1*1502), whereas others almost no affinity (e.g., DRB1*1101); and (iii) DR-binding motifs described in the literature can explain some of the allele-specific interactions between mutated peptides and DR complexes. Therefore, some mutated Ras- and p53-derived peptides could be tumor-specific antigens recognized by CD4+ T cells in an HLA-DR allele-specific manner.

症例は78歳女性．閉塞性黄疸及び十二指腸狭窄による嘔吐を主訴に来院．腹部造影CTでは，十二指腸と膵頭部の間に帯状の低吸収域を認め，十二指腸に接する膵内に10mm大の腫瘤性病変が認められた．十二指腸球部からのEUS走査では十二指腸に接する膵辺縁に低エコー腫瘤とこれに連続して，groove領域，十二指腸壁に不整に拡がる境界不明瞭な低エコー像を認めた．また十二指腸狭窄部からの内視鏡的生検にて腺癌が検出された．以上よりgroove領域に浸潤した膵癌と診断し亜全胃温存膵頭十二指腸切除術を施行した．病理組織学的には十二指腸に接する膵領域より発生しgroove領域及び十二指腸へ浸潤性増殖を示す25×20mmの膵癌（T3N0M0 pStageIII）であった．これまでgroove pancreatic carcinomaの報告においてEUS所見に言及した例は少なく貴重な症例と考え報告する．

A method of evaluating effective irradiance is discussed for photoresist with the reciprocity law failure property irradiated by fluctuating radiation. The resultant formula for evaluating effective irradiance suggests that both reciprocity law failure and time response for the photochemical reaction should be considered when evaluating effective irradiance. This method is used in an irradiance meter which measures the distribution of near ultraviolet effective irradiance. This irradiance meter is applied to the photoresist exposure process in color TV picture tube fabrication. This meter automatically measures relative irradiance over 51 points on the phosphor screen of a color TV picture tube, in about 1 min. Reproducibility and accuracy for measured values are estimated to be about 0.2% and 1%, respectively. Absolute irradiance is measured at the center of the screen, with an accuracy of about 3%.

Chemical and electric properties of the anodic oxide films of GaAs and GaP are investigated under various annealing conditions. Analysis of the oxidation current proves that the oxide grows at constant field condition on p-GaAs and at constant resistivity condition on n-GaAs under the pseudo constant voltage biasing. Proper annealing improves C-V curves of a p-GaAs MOS diode to almost the ideal case, while the improvement is small for an n-GaAs diode. It is found that the change of the C-V and G-V curves is influenced by annealing temperatures rather than by annealing gases. Effects of the Bias-Temperature (BT) treatment are also shown.

Background Although neuroendocrine tumors are most commonly found in the digestive system, neuroendocrine tumors originating from the bile duct are rare, and neuroendocrine carcinomas derived from the perihilar bile duct are extremely rare. This report presents the clinical course and clinicopathological features of neuroendocrine carcinomas arising from the extrahepatic bile duct. Case presentation A 70-year-old Japanese woman was preoperatively diagnosed with perihilar cholangiocarcinoma, and a radical resection with an extended left hepatic lobectomy and a choledochojejunostomy was performed. From the histopathological findings, we diagnosed the tumor as a neuroendocrine carcinoma of the bile duct (small cell type) with lymph node metastasis. The patient was treated with the same adjuvant chemotherapy as that used for small cell carcinoma of the lung. At 10 months after surgery, there was no recurrence of the disease. Conclusion Neuroendocrine carcinoma of the extrahepatic biliary tracts is a very rare and highly malignant disease with a poor prognosis. A multidisciplinary approach could improve the prognosis for this neoplasm.

A simple and effective new technique has been demonstrated which improves markedly the chemical and electrical properties of heat-treated anodic oxide films on GaAs. This technique should facilitate the use of anodic oxides in innovative GaAs devices.

Passivation of GaAS surface is important in stabilizing device performance and preventing degradation caused from surface. Several methods of forming insulating films are surveyed and electrical properties of insulating films and the interface are discussed for GaAs MOS diodes with an anodic oxide film on the basis of experimental results on capacitance vs. voltage characteristics, capacitance transient and DLTS spectra. A model is proposed to interprete the observed behaviors of MOS diodes. Some applications are shown and the microwave capability of 1.5 µm gate MOS FETs