No abstract

SummaryPolyreactive antibodies (Abs) constitute a major proportion of the early Ab repertoire and are an important component of the natural defense mechanisms against infections. They are primarily immunoglobulin M (IgM) and bind a variety of structurally dissimilar self and exogenous antigens (Ags) with moderate affinity. We analyzed the contribution of Ig polyvalency and of heavy (H) and light (L) chain variable (V) regions to polyreactivity in recombinatorial experiments involving the V.-diversity(D)-JH and VK-J~ gene segments of a human polyreactive IgM, monoclonal antibody 55 (mAb55), and those of a human monoreactive anti-insulin IgG, mAb13, in an in vitro Cyl and C~ human expression system. These mAbs are virtually identical in their V, and VK gene segment sequences. First, we expressed the V.-D-J. and V~-J~ genes of the IgM mAb55 as V segments of an IgG molecule. The bivalent recombinant IgG Ab bound multiple Ags with an efficiency only slightly lower than that of the original decavalent IgM mAb55, suggesting that class switch to IgG does not affect the Ig polyreactivity. Second, we coexpressed the mAb55-derived H or K chain with the mAb13-derived K or H chain, respectively. The hybrid IgG Ab bearing the mAb55-derived H chain V segment paired with the mAb13-derived ~ V segment, but not that bearing the mAb13-derived H chain V segment paired with the mAb55-derived K V segment, bound multiple Ags, suggesting that the Ig H chain plays a major role in the Ig polyreactivity. Third, we shuffled the framework 1 (FR1) -FtL3 and complementarity determining region 3 (CDR3) regions of the H and K chain V segments of the mAB55-derived IgG molecule with the corresponding regions of the monoreactive IgG mAb13. The mAb55-derived IgG molecule lost polyreactivity when the H chain CDR3, but not the FR1-FR3 region, was replaced by the corresponding region of mAb13, suggesting that within the H chain, the CDR3 provides the major structural correlate for multiple Ag-binding. This was formally proved by the multiple Ag-binding of the originally monoreactive mAb13-derived IgG molecule grafted with the mAb55-derived H chain CDR3. The polyreactivity of this chimeric IgG was maximized by grafting of the mAb55-derived K chain FK1-FIL3, but not that of the K chain CDK3. The mAb55-derived K chain FR1-FK3 (an unmutated V~ 325 segment), however, failed to yield a polyreactive Ab when grafted onto an IgG that was in all other parts identical with mAb13. Rather, this chimeric molecule showed full specificity for insulin. Thus, the polyreactivity of the human mAb55 can be fully preserved after Ig class switch, and depends primarily on the contribution of structures that are generated through somatic rearrangement events (H chain CDK3), and structures that represent the expression of an unmutated gene (VK 325 segment). Sera of healthy humans and animals contain natural antibodies (Abs) that react with a variety of self and exogenous Ags. Most natural mAbs generated from humans and mice are polyreactive, i.e., they bind multiple, even very...

The expression of vascular endothelial growth factor was one of the most important prognostic factors in completely resected non-small-cell lung cancer, especially in squamous cell carcinoma.

BACKGROUND.The clinicopathologic features of young and elderly patients with gastric carcinoma have been analyzed. METHODS. We analyzed the data from 174 patients with gastric carcinoma age 40 years and younger and from 356 patients with gastric carcinoma age 70 years and older who were surgically treated at the Department of Surgery 11, Kyushu University, Japan. RESULTS. The rate of multiple gastric carcinomas was 2.9% (5/174) for the young patients and 13.2% (471356) for the elderly. In subjects older than 70 years, male patients predominated, tumors were smaller, differentiated lesions more common, vascular involvement more frequent, tumors were less infiltrative, and the rate of liver metastasis was higher. For patients younger than age 40 years, undifferentiated type with infiltrative growth was frequent and the rate of liver metastasis was higher. There were no differences in the positive rate of p53 overexpression and the proliferating activity of the cancer cells determined by PCNA LI, between the young and elderly patients. The survival rate after curative resection was lower for the elderly compared with that for the young patients; hematogenous recurrence was higher in the former. CONCLUSIONS. The clinicopathological features of gastric carcinoma differed between the young and elderly patients, and these differences should be considered

WIDE PREVALENCE OF INTEREST in early gastric cancer has contributed to a considerable rise in the number of cases in both Japan and Western countries.'-5 The prognosis after surgery for early gastric cancer is generally favorable, and the 5-year survival rate reported in the literature from Japan exceeds 90%'. 6-8 Although early gastric cancer is potentially curable by surgery, there are cases of a recurrence after curative resection. We reviewed our experience with early gastric cancer during a 24-year period and evaluated the following: (1) incidence and patterns of recurrence, (2) characteristic findings in the recurrent cases related to the clinicopathologic nature or surgical procedures, and (3) possibility of further improvement in the prognosis of early gastric cancer.