Vascularised bone grafts in the treatment of long bone defects

Reconstruction of large bony defects of long bones was performed using vascularised fibular grafts in four patients at the Department of Orthopaedic Surgery of the University of Ioannina Medical School. Indications for grafting procedures in this small series had been the loss of bone due to the extensive resection of avascular and necrotic bone from septic pseudoarthrosis in three patients and congenital pseudarthrosis secondary to neurofibromatosis in a child. Primary skeletal union with graft hypertrophy occurred in three of the patients. The fourth patient had an asymptomatic nonunion at the proximal end of the graft. The result in each patient was the presence of a well-aligned limb that had normal or nearly normal motion and acceptable length. © 1994 Wiley-Liss, Inc.     

Evidence for distinct epitopes on human IgG with T cell proliferative and suppressor function

The Fc or pFc' fragments of the human IgG were demonstrated to exert different effects on murine T lymphocyte subsets. Thus, murine lymph node (LN) T cells were specifically induced to proliferate in vitro to pFc' after priming in vivo. This proliferation could be inhibited, either by depleting the responding LN population of macrophages, or by monoclonal antibodies specific for responder haplotype Ia antigenic determinants. Priming in vivo and subsequent restimulation in vitro with Fc resulted in the activation of a suppressor T cell subpopulation which, in an antigen-specific manner, could highly suppress proliferative responses. T cell subset isolation showed that the pFc'-specific proliferation was performed by Lyt-1+2- cells whereas the suppressor Fc-specific cells were of Lyt-1-2+ phenotype. Our data demonstrate that distinct epitopes on the human gamma chain induce either Ir gene-restricted T cell proliferation (pFc' fragment) or T cell suppressor function (Fc fragment).     

Axillary lymph node cellular immune response to HER-2/neu peptides in patients with carcinoma of the breast.

HER-2/neu peptides have recently been shown to induce a proliferative response by peripheral CD4(+) T cells in breast cancer patients. To investigate potential differences in the local cellular immune response between breast cancer patients with and without nodal metastases, lymphocytes were isolated from axillary lymph nodes from patients with breast cancer, and proliferative and cytokine responses to HER-2/neu peptides were determined. Freshly isolated lymphocytes from lymph nodes of 7 women undergoing surgery for invasive breast cancer were plated at 20 x 10(5) cells per well in triplicate. Cells were stimulated with HER-2/neu peptides at 50 microg/ml and with control antigens. Incorporation of tritium-labeled thymidine was determined 4 days later. The levels of the cytokines interferon-gamma (IFN-gamma), interleukin-4 (IL-4), and IL-10 were determined at priming and at restimulation with HER-2/neu peptides using a cytokine-specific, double-sandwich, enzyme-linked immunosorbent assay (ELISA). Lymphocytes isolated from the axillary lymph nodes of the patients mounted significant cellular immune response to HER-2/neu peptides, manifested by proliferation and specific cytokine elaboration. Proliferative responses to HER-2/neu peptides were seen in lymphocytes of patients with and without overexpression of HER-2/neu in the primary tumor. In some patients, the proliferative response to HER-2/neu peptides in lymphocytes from lymph nodes with metastases was absent or blunted compared with the response in lymphocytes from lymph nodes without metastases from the same patient (p < 0.05). HER-2/neu peptides induced a predominantly T helper type 1 (Th1) pattern of cytokine response in nodal lymphocytes isolated from breast cancer patients. A Th1-specific cytokine production pattern was maintained at priming and restimulation with HER-2/neu peptides and was amplified with IL-12 costimulation. These results indicate that HER-2/neu peptides can activate T cells in draining lymph nodes from women with invasive breast cancer. This activation is associated with a predominantly Th1 cytokine response, which suggests that conditioning with HER-2/neu peptides may be of value in the development of breast cancer vaccines.     

The role of self-Ia antigens in the murine mixed lymphocyte response

Mouse splenic macrophages (M phi) were tested for their ability to potentiate in vitro allogeneic mixed lymphocyte response (MLR) of highly purified syngeneic responder T cells against allogeneic M phi. It was shown that even extremely low numbers of M phi syngeneic to the responder T cells were able to induce significantly stronger MLR. This potentiating effect was demonstrated to be expressed via the self-Ia antigens present on the surface of syngeneic M phi. The functional involvement of self-Ia antigens was substantiated by two approaches: (a) by using monoclonal antibodies specific for I-region determinants of the responder haplotype M phi and (b) by setting up MLR cultures with stimulator M phi of (responder X stimulator) F1 origin which express both self- and allo-Ia antigens. The results obtained in this study demonstrate that the presentation of self-Ia antigens, in conjunction with the recognition of allo-major histocompatibility complex antigens, are required for in vitro primary MLR.     

Hydrocephalus in primary intradural spinal cord tumors: a systematic review of the literature in the pediatric population

Neurosurgical Review - Hydrocephalus in children with primary intradural spinal cord tumors is exceedingly rare. Herewith, we performed a systematic literature review to address epidemiology,...     

Dissimilar tcr v-Beta frequencies in til from different sites of the same tumor

Tumor infiltrating lymphocytes (TIL) cultured long term in media containing IL-2 were shown to mediate in vitro and in vivo anti-tumor responses. To understand the anti-tumor activity of TIL T cells, we used polymerase chain reaction (PCR) to characterize the TCR Vbeta repertoire of ovarian TIL which were isolated from three tumor sites of the same patient at the same time and cultured under identical conditions, resulting in CD3+ cells with similar CD8:CD4 ratios. TIL isolated from ovary and ascites expressed a broad distribution of Vbeta repertoire, while the Vbeta phenotype of the TIL from a secondary tumor (omentum) was more restricted. After 5 months, cultured TIL from the primary tumor (ovary) maintained a diverse TCR Vbeta repertoire, but the Vbeta phenotype of TIL from the secondary site was dominated by the Vbeta-1, -11 and -14 families. Importantly, the percentages of Vbeta-11 and Vbeta-1 expression in both omentum and ovary TIL at 3 and 5 months was found to correlate with the levels of lysis of the tumor localized to omentum (p =0.003 and p=0.014, respectively). No statistical correlation was found between cytotoxicity and the use of any other individual Vbeta families or the sum of any other families, including TCR Vbeta-3 or -20 found increased at certain time points. This suggests that where certain TCR Vbeta families are selected in tumor reactive T cells this selection may reflect tumor Ag recognition at either primary or distant tumor sites. To our knowledge, this is the first documentation of complete TCR Vbeta repertoire of ovarian TIL and of a correlation between Vbeta usage and tumor lysis, by effectors from different sites.     

Gluten neuropathy: electrophysiological progression and HLA associations

Journal of Neurology - Gluten neuropathy (GN) is the term used to describe peripheral neuropathy that occurs in patients with gluten sensitivity (GS) or coeliac disease (CD) in the absence of other...