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T James

Publications and source records attributed to T James.

At least 55 records · Page 3Linked to original sources

Silphion.

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History, Ancient↗

Induction of peripheral tolerance by intrathymic inoculation of soluble alloantigens: evidence for the role of host antigen-presenting cells and suppressor cell mechanism.

Intrathymic (IT) inoculation of soluble alloantigens (Ag) obtained from 3 M KCl extracts of resting T-cells induces donor-specific tolerance to cardiac allografts and islet allografts. This study examined the cellular basis of induction of transplantation tolerance by IT injection of soluble Ag. Our results show that while IT inoculation of 2 mg soluble donor Ag on Day -7 relative to Lewis islet transplantation induced specific unresponsiveness to islet allografts (> 200 days) in naive diabetic recipients, IT inoculation of 2 mg soluble Ag on the same day as islet transplantation did not prolong islet allograft survival in the same Lewis-to-WF rat combination. To define the role of donor APCs in intrathymic tolerance, we showed that IT injection of an admixture of 1 x 10(4) donor DC and 2 mg soluble Ag caused acute islet graft rejection. In contrast, addition of 1 x 10(4) recipient-type DC to the IT inoculum did not prevent long-term graft survival. This finding suggests that while the presence of donor APCs in the inoculum does not appear necessary for IT-alloantigen to induce peripheral tolerance, presentation of the soluble Ag in the thymus is dependent on host APCs. This conclusion is supported by our in vitro MLR experiments which showed that in vivo WF-Ag-primed Lewis T-cells proliferated specifically to WF-soluble Ag and that the response was enhanced 14-fold by the addition of responder-type DC. Addition of anti-Lewis MHC class II mAb specifically blocked the alloresponse, thus suggesting that in vivo Ag-primed T-cells are capable of recognizing and proliferating in response to allopeptides presented by responder APCs. We also showed that adoptive transfer of syngeneic naive T-cells into unresponsive recipients failed to break tolerance to long-term surviving islet allografts. This finding suggests that tolerance in this model is not due to a lack of T help. On the other hand, the adoptive transfer of spleen cells, but not sera, from the unresponsive WF recipients bearing long-term (> 120 days) functioning Lewis islets resulted in prolonged survival of donor-type but not third-party islet allografts in secondary syngeneic hosts. Our data suggest that the tolerogenic effect of IT inoculation of soluble Ag is dependent on the indirect pathway of Ag presentation and clonal deletion of alloreactive T-cells in the thymus, while suppressor/regulatory mechanism may be involved in the maintenance of peripheral tolerance.

Animals↗

Characterization of a new class of transcribed repetitive DNA sequence which also exists as a hybrid with HP1 mRNA; potential for site-specific recombination in Drosophila melanogaster.

A new class of dispersed repetitive DNA designated as vivi-sequence (VS) has been identified in Drosophila. It is relatively AT rich and is transcribed. The VS transcription is developmentally regulated and generates multiple transcripts. A hybrid transcript, designated fl-cDNA, has been identified in which a small segment of the VS is fused to the 5' end of an unrelated structural gene transcript coding for the heterochromatin protein HP1. The VS has recombination signal sequences (RSS) characteristic of vertebrate immunoglobulin genes. Such sequences are also present in the HP1 DNA. In both cases the recombination signal sequences are found close to the junction between HP1 and the VS in fl-cDNA. There is additional sequence identity both 5' and 3' of the junction between HP1 and the VS in fl-cDNA. We propose that (a) the HP1-VS composite transcript represented by the fl-cDNA may be the product of recombination between the two sequences, (b) that the process is mediated by the RSS and/or the DNA downstream of the junction between HP1 and the VS and (c) that the recombination event may lead to the inactivation of the HP1 gene in a cell and tissue specific manner.

Animals↗

Criteria and scientific basis for RDA (PRI).

Nutritional science is blossoming once more and the attempts by national or European Union communities to specify an appropriate diet for long-term health is becoming ever more difficult. The issue of antioxidants is also becoming very complex and it seems likely that over the next decade an integration of nutritional physiology, cell biology and epidemiology will allow us to produce a more coherent overview of the interplay between dietary bioactive molecules and the relative amount of antioxidant micronutrients. Once this understanding emerges then I foresee the need to revise--perhaps substantially--this first attempt by the SCF to produce European figures for the requirements for nutrients.

Europe↗

Prevention of cyclosporine-induced syngeneic graft-versus-host disease in bone marrow transplantation by UV-B irradiated bone marrow cells.

UV-B irradiation of allogeneic rat bone marrow cells (BMC) transplanted into lethally gamma-irradiated recipients prevents GVHD and induces stable complete hematopoietic chimerism. Cyclosporine (CsA), an effective immunosuppressive agent, causes an autoimmune syndrome termed syngeneic GVHD in syngeneic radiation chimeras following discontinuation of CsA. To understand the in vivo interactions of CsA with UV-B modulated syngeneic bone marrow transplant (BMT), as this is essential before clinical use, we studied the effects of CsA therapy in recipients of UV-B irradiated donor BMT in the rat model. Lethally irradiated (10.5 Gy) Lewis recipients of naive or UV-B irradiated syngeneic BMT (admixture of 10(8) BMC and 5 x 10(6) spleen cells) were treated with CsA (i.m. 12.5 mg/kg/day) for 30 consecutive days after BMT. The results show that all irradiated Lewis recipients of syngeneic BMT modulated with 700 J/m2 UV-B were hematologically fully reconstituted in 25-35 days and survived their normal life span. In contrast, all lethally irradiated recipients of untreated BMT that received CsA for 30 days developed lethal acute syngeneic GVHD 7-12 days after CsA withdrawal. Of interest is the finding that while higher doses of UV-B (500-700 J/m2) irradiation of BMC prior to transplantation into CsA-treated animals prevented hemopoietic reconstitution, lower doses (100-300 J/m2) allowed for hemopoietic recovery and, in addition, prevented the development of syngeneic GVHD following the discontinuation of CsA. The development of syngeneic GVHD was dependent on the presence of the thymus and did not occur in thymectomized recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Vaginal birth after cesarean section in a university setting.

Despite numerous reports in the literature almost universally endorsing the safety of a trial of labor after a prior cesarean section, it is used in only a small fraction of eligible patients. Our investigation, conducted at the University of Louisville, examines the safety of such a protocol. Two thousand seven hundred fifty-seven patients were delivered during one year; 282 had a history of at least one prior cesarean section. Of the 259 patients eligible, 218 (84%) underwent a trial of labor, and 168/218 (77%) were delivered vaginally. There were 6 cases of uterine dehiscence and 1 uterine rupture. No hysterectomies were performed. Maternal morbidity was significantly greater in the failed trial-of-labor group. There was one perinatal death that was unrelated to a trial of labor. A previous diagnosis of cephalopelvic disproportion or failure to progress did not preclude a trial of labor, and 69% of these patients delivered vaginally. Our data suggest that a trial of labor following one or more previous cesarean sections is a safe option in a carefully selected population.

Cesarean Section↗

Prevention of graft-versus-host disease and bone marrow rejection: kinetics of induction of tolerance by UVB modulation of accessory cells and T cells in the bone marrow inoculum.

UVB irradiation (700 J/m2) of bone marrow cells (UVB-BMC) before transplantation into lethally gamma-irradiated (10.5 Gy) allogeneic rats prevents graft-versus-host disease (GVHD) and induces a stable complete lymphohematopoietic chimerism. To better understand the underlying mechanism of the development of stable chimerism and induction of tolerance to donor organs in this model, we examined if the addition of T cells or dendritic cells (DC), as antigen presenting cells (APC), would restore the immunogenicity of UVB-BMC in in vitro mixed lymphocyte reaction (MLR) and induce in vivo bone marrow (BM) graft rejection. Whereas gamma-irradiated, unfractionated BMC induce allogeneic T cells to proliferate, UVB irradiation of BMC abolishes the stimulatory capacity of such cells in a primary MLR. Addition of purified T cells, CD4+ T cells, CD8+ T cells or B cells, respectively, failed to restore the capacity of UVB-BMC to stimulate allogeneic T-cell proliferation. In contrast, the addition of only a small number of splenic accessory cells or purified DC, which by themselves were relatively ineffective in stimulating T-cell proliferation, restored the accessory function and the allostimulatory capacity of UVB-BMC. To define the molecular defect induced by UVB irradiation, cytokines were added as costimulatory factors to primary MLRs and the results showed that the addition of interleukin (IL)-2 or IL-6 but not IL-1 or interferon gamma (IFN-gamma) restored the stimulatory capacity of UVB BMC. This finding suggests that UVB may alter the production, and/or utilization of IL-2 and IL-6 either at the membrane or cytoplasmic level. Parallel in vivo studies showed that addition of DC to UVB BM inoculum resulted in failure of BM engraftment, whereas addition of T cells led to development of fatal GVHD, thus suggesting that UVB modulation of accessory cells reduces graft immunogenicity and prevents BMT rejection, while modulation of T cells prevents GVHD. Our data provide evidence that UVB modulation of APC and mature T cells contained within BMC is potentially useful in preventing GVHD without endangering successful engraftment and may serve as a model for induction of adult chimerism and tolerance without the development of GVHD.

Animals↗

Fine-needle aspiration diagnosis of intra-thoracic and intra-abdominal lesions: review of experience in the pediatric age group.

Review of fine-needle aspiration (FNA) smears from 121 pediatric patients with intra-thoracic and intra-abdominal lesions revealed 42 (34.7%) cases of neoplasms, 35 (28.9%) cases of tuberculosis, 12 (9.9%) cases of non-tuberculous inflammations, 4 (3.3%) cases of benign cystic lesions, and 28 (23.1%) inadequate/inconclusive cases. The age of the patients ranged from 20 days to 18 yr. Ultrasound and/or CT study done in 105 cases localized the lesions in following common sites: lungs (19 cases), mediastinum (22 cases), liver (14 cases), intestines (11 cases), and lymph nodes (17 cases). The neoplastic lesions consisted of 39 malignant, one suspicious, and two benign neoplasms. Among the neoplasms, the small round cell tumors were the most frequent (27 cases), followed by germ cell tumors (eight cases) and miscellaneous neoplasms (seven cases). The common small round cell tumors were non-Hodgkins lymphoma (eight cases), hepatoblastoma (seven cases), neuroblastoma (five cases), and nephroblastoma (three cases). A combined clinical, imaging, and FNA cytology approach was found to be useful in arriving at a tissue diagnosis.

Abdomen↗

Induction of specific unresponsiveness to rat islet allografts by intrathymic UVB donor spleen cells.

Recently, we showed that intrathymic (i.t.) injection of UVB-irradiated (600 J/m2) spleen cells induces donor-specific unresponsiveness to cardiac allografts in the sublethally irradiated (200 rads, TBI) recipients in the Lewis-to-ACI rat combination. This study examined if i.t. injection of UVB donor SC could induce specific unresponsiveness to neovascularized (islet) allografts in the same rat combination of Lewis-to-ACI. Streptozotocin-induced diabetic ACI rats pretreated with sublethal TBI (200 rads) 7 days prior to intraportal transplantation of freshly isolated Lewis islets reject their grafts in 10.2 +/- 2.9 days compared with rejection of islets in 8.5 +/- 2.6 days in unmodified controls. Recipient pretreatment with i.t. injection of UVB donor SC combined with sublethal TBI (200 rads) 7 days prior to islet transplantation induced indefinite graft survival (> 200 days) in 3 of 7 animals. Similar treatment failed to prevent acute rejection of third-party (WF) islets, thus demonstrating donor-specificity. Treatment with sublethal TBI (200 rads) on the day of islet transplantation led to permanent graft survival in 2 of 5 animals that received i.t. inoculation of UVB donor SC 7 days prior to islet transplantation. Conditioning of the recipients with a sublethal TBI dose of 300 rads on the day of islet transplantation, which alone delayed graft rejection for only 19 days, led to indefinite graft survival (> 150 days) in all animals pretreated with i.t. injection of UVB donor SC. Extrathymic inoculation of donor UVB SC via subcutaneous, intraperitoneal, intratesticular, and intravenous routes, respectively in similarly prepared animals failed to prolong islet survival, thus confirming the privileged position of the thymus in the induction of tolerance. Our findings suggest that this new strategy of immunomodulation with donor UVB SC is potentially useful for induction of donor-specific unresponsiveness.

Animals↗