Adoptively transferred CD4+ lymphocytes from CD8 -/- mice are sufficient to mediate the rejection of MHC class II or class I disparate skin grafts

Recent studies revealed that CD4+ cells initiate allograft rejection through direct recognition of allogeneic MHC class II Ags and indirect recognition of MHC peptides processed by self APCs. Both pathways were shown to help CD8+ cells that eventually lysed allogeneic MHC class I-presenting targets. There was little evidence, however, that CD4+ cells are sufficient for graft rejection. We studied skin graft rejection by CD8-deficient (CD8 -/-) mice. We showed that BALB/cJ(H-2d) CD8 -/- mice could reject allogeneic skin from C57BL/6J(H-2b) mice deficient in MHC class I or in MHC class II Ags. To understand the role of CD4+ cells in this process, we isolated them from CD8 -/- mice and transferred them to BALB/cJ nude mice that had been grafted with allogeneic skin (H-2b) from animals deficient in MHC class I or MHC class II. Nude mice injected with CD4+ cells rejected MHC class II and, albeit more slowly, MHC class I disparate skins. We showed in vitro evidence that CD4+ cells were not cytotoxic toward MHC class I or MHC class II disparate targets and that they recognized MHC class I allogeneic targets through indirect recognition. CD4+ cells produced Th1 cytokines, but not IL-4, following stimulation with allogeneic cells. Furthermore, intragraft TNF-alpha was elevated in skin grafted onto nude mice reconstituted with CD4+ cells compared with nonreconstituted mice. This suggests that MHC class II- or MHC class I-guided CD4+ cells alone are sufficient to induce rejection by the generation of cytokine-induced lesions.     

A case of Ohtahara syndrome with cytochrome oxidase deficiency

Ohtahara syndrome is a rare cause of epileptic seizures during the neonatal period. This is believed to be the first report of this syndrome with a specific metabolic defect. Defects in respiratory chain function may be more common than previously assumed in patients with this epilepsy syndrome.     

Treatment of rheumatoid arthritis with IL-1 inhibitors

Extensive evidence from both in vivo and in vitro experiments indicate that IL-1, a prototypic proinflammatory cytokine, is involved in the mechanisms that lead to progressive joint destruction in RA. IL-1Ra, a member of the IL-1 family, binds IL-1 receptors but does not induce any cellular responses. IL-1Ra competitively inhibits the binding of IL-1 to its cell surface receptors and thus, acts as an endogenous antiinflammatory mediator. However, the results of several studies suggest that a relatively deficient production in IL-1Ra as compared to that of IL-1 in RA synovium may predispose to the perpetuation of chronic inflammation. Systemic administration of IL-1Ra, or local delivery into the joint by gene therapy, in different experimental animal models of arthritis attenuated the severity of the inflammatory response and reduced articular destruction. In addition, treatment of rheumatoid patients with IL-1Ra led to an improvement in different clinical and biological parameters and to a reduction in the radiological signs of joint erosions. Encouraging results also have been reported in both in vitro and in vivo experimental animal models of arthritis through using other strategies designed to block the effects of IL-1 at the level of production, prevent the binding of IL-1 to its cell surface receptors, or interfere with the effects of IL-1 at the post-receptor level.     

The addition of paclitaxel to continuous infusion 5-fluorouracil is an active regimen for metastatic breast cancer

We investigated tissue staining for Bcl-2 and Bax proteins, which regulate apoptosis, as indicators of chemotherapeutic effect in patients with gastric cancer. In 23 patients with gastric carcinoma biopsy specimens were obtained endoscopically prior to chemotherapy and stained immunohistochemically with anti-Bcl-2 and anti-Bax antibodies. Patients then were treated with continuous infusion of 5-FU and cisplatin. No correlation was seen between chemotherapeutic effect and Bcl-2 or Bax alone. However, among the Bax-positive cases, the patients with Bcl-2-positive tumors were significantly more chemoresistant (p = 0.036) and had worse prognoses (p = 0.008) than Bcl-2-negative cases. Therefore, immunohistochemical staining for Bcl-2 protein may predict chemotherapeutic efficacy or guide specific therapeutic choices in treating Bax-positive tumors.     

A ten year study of medullary carcinoma of the breast

In this large series of patients treated for medullary carcinoma of the breast by radical mastectomy, the over-all five year survival rate was 63.7 per cent and the ten year survival rate, 49.5 per cent. Although survival was adversely affected by axillary lymph node involvement, there was an equal incidence of such involvement, there was an equal incidence of such involvement in tumors less than 4 centimeters compared with those greater than 4 centimeters in size; however, patients with tumors greater than 4 centimeters in size fared poorer categorically than did those with smaller lesions. Women in the premenopausal period had one-third of the cancers and had a significantly better survival rate than did those in the postmenopausal period, despite a similar incidence of axillary lymph node involvement. Medullary carcinoma is among the small group of malignant tumors of the breast that have distinctly better five and ten year survival rates than other more common varieties.     

New technique for lesser saphenous vein harvesting

A new technique using the Thompson self-retaining retractor system (Thompson Surgical Instruments, Inc, Traverse City, MI) to harvest lesser saphenous veins is presented. This modification, used in 10 patients undergoing redo myocardial revascularization, provided a rapid, comfortable, and convenient method for harvesting lesser saphenous veins.