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Biomedical subjects

X Cai

Publications and source records attributed to X Cai.

208 records · Page 12Linked to original sources

Transplantation of the small intestine: the pathologist's perspective.

Small-bowel transplantation is now ready for clinical trials. The surgical techniques and methods for immunosuppression and monitoring bowel status have been developed in animal models over the past 30 years. Several attempts at small-bowel transplantation in humans have already been reported. In the course of future trials, pathologists will be involved in the monitoring of the posttransplant course by mucosal biopsies and functional studies, including maltose and xylose absorption tests. The morphology of rejection has been studied in canine and rat models. Activated lymphocytes and plasma cells infiltrate the lamina propria and invade crypt epithelium, causing "cryptitis." Villous blunting ensues, resulting eventually in necrosis. Graft survival without immunosuppression is about 10 days. Under Cyclosporine immunosuppression, a lymphoplasmacytic infiltrate has been noted around nerves and vessels in the submucosa. The overlying mucosa may be relatively normal. End-stage bowel is characterized by a contracted, scarred mass. Due to the large amount of lymphoid tissue in the allograft, graft-versus-host disease is a significant problem in small-bowel transplantation.

Graft Rejection↗

Subunit Composition of Glutamine Synthetase Isozymes from Root Nodules of Bean (Phaseolus vulgaris L.).

Glutamine synthetase from bean nodules can be separated into two isoforms, GS(n1) and GS(n2). A purification protocol has been developed. It included protamine sulfate precipitation, ammonium sulfate fractionation, anthranilate-affinity chromatography, Dye-Matrex (Orange A) chromatography, and diethylaminoethyl-cellulose ion-exchange chromatography. GS(n1) and GS(n2) have been purified to homogeneity. Subunit structure analysis using two-dimensional polyacrylamide gel electrophoresis revealed that GS(n1) was composed of two different types of subunit polypeptides. They differed in isoelectric points (6.0 and 6.3) but had the same molecular weights (46,000 Daltons). GS(n2) was composed of only one type of subunit polypeptide. It had an isoelectric point of 6.0 and a molecular weight of 46,000 Daltons. It was apparently identical to one of the polypeptides found in GS(n1). Glutamine synthetase holoenzyme consisted of eight subunits. In the nodule there are two different types of glutamine synthetase subunit polypeptides. Random combinations of the polypeptides should generate nine different isozymes. Our electrophoretic analysis revealed that GS(n2) was but one of the isozymes, and GS(n1) was a composite of the other eight. Hence, nodule glutamine synthetase isozymes were homo-octameric as well as hetero-octameric.

Journal Article↗

Immunomagnetic T-lymphocyte depletion (ITLD) of rat bone marrow using OX-19 monoclonal antibody.

Graft versus host disease (GVHD) may be abrogated and host survival prolonged by in vitro depletion of T lymphocytes from bone marrow (BM) prior to allotransplantation. Using a mouse anti-rat pan T-lymphocyte monoclonal antibody (OX19) bound to monosized, magnetic, polymer beads, T lymphocytes were removed in vitro from normal bone marrow. The removal of the T lymphocytes was confirmed by flow cytometry. Injection of the T-lymphocyte-depleted bone marrow into fully allogeneic rats prevents the induction of GVHD and prolongs host survival.

Animals↗

Induction of stable chimerism and elimination of graft-versus-host disease by depletion of T lymphocytes from bone marrow using immunomagnetic beads.

The goal of transplantation is the induction of immunologic tolerance. At present, nonspecific immunosuppression is used to prevent graft rejection and, commonly, graft-versus-host disease (GVHD). Nevertheless, nonspecific immunosuppressive therapy is frequently complicated by infection, malignant tumors, and drug toxicity. In order to examine whether hematopoietic chimerism can be used to induce specific allograft tolerance, we have reconstituted lethally irradiated Lewis rats with ACI bone marrow that has been depleted of T cells with use of immunomagnetic beads. This technique consists of binding OX-19, a mouse anti-rat pan-T lymphocyte monoclonal antibody, to magnetic polymer beads. Mixing of bone marrow or splenocytes with the bead/OX-19 complexes, followed by magnetic separation, results in significant depletion of T cells with minimal nonspecific cell loss. Immunomagnetic T-cell depletion of bone marrow, followed by reconstitution of a lethally irradiated host, allows for the development of stable, mixed hematopoietic chimerae without evidence of GVHD. These hosts are immunocompetent by clinical criteria. Recipients of untreated donor bone marrow that did or did not receive nonspecific immunosuppression demonstrated varying degrees of GVHD and reduced survival. The ability to rapidly and simply deplete T lymphocytes from bone marrow and produce stable, immunocompetent hematopoietic chimerae without GVHD may be an important method for tolerance induction to vascularized allografts.

Animals↗

Induction of donor-specific transplantation tolerance to skin and cardiac allografts using mixed chimerism in (A + B-->A) in rats.

Mixed allogeneic chimerism (A + B-->A) was induced in rats by reconstitution of lethally irradiated LEW recipients with a mixture of T-cell depleted (TCD) syngeneic and TCD allogeneic ACI bone marrow. Thirty-seven percent of animals repopulated as stable mixed lymphopoietic chimeras, while the remainder had no detectable allogeneic chimerism. When evaluated for evidence of donor-specific transplantation tolerance, only those recipients with detectable allogeneic lymphoid chimerism exhibited acceptance of donor-specific skin and cardiac allografts. Despite transplantation over a major histocompatibility complex (MHC)- and minor-disparate barrier, animals accepted donor-specific ACI skin and primarily vascularized cardiac allografts permanently, while rejecting third party Brown Norway (BN) grafts. The tolerance induced was also donor-specific in vitro as evidenced by specific hyporeactivity to the allogeneic donor lymphoid elements, yet normal reactivity to MHC-disparate third party rat lymphoid cells. This model for mixed chimerism in the rat will be advantageous to investigate specific transplantation tolerance to primarily vascularized solid organ grafts that can be performed with relative ease in the rat, but not in the mouse, and may provide a method to study the potential existence of organ- or tissue-specific alloantigens in primarily vascularized solid organ allografts.

Animals↗

Treatment of acute promyelocytic leukemia with arsenic trioxide: clinical and basic studies.

Arsenic trioxide (As2O3) has recently been identified as an effective drug in the treatment of newly diagnosed and relapsed acute promyelocytic leukemia (APL) without cross-resistance to all-trans retinoic acid and achieved complete remission rates of 80-90% according to most reports. With intravenous infusion at a dose of 0.08-0.16 mg/kg daily, a course of 28-42 days is required to induce remission. As2O3 in combination with chemotherapy as postremission therapy results in longer survival than arsenic alone. In vitro, As2O3 exerts dose-dependent dual effect; triggering apoptosis at relatively high concentration (0.5-2.0 micromol/l), which is associated with the disruption of mitochondrial transmembrane potentials, while inducing partial differentiation at low concentration (0.1-0.5 micromol/l), which might be related to retinoic acid signaling pathway. Importantly, at both concentrations, As2O3 can degrade PML (promyelocytic leukemia) -RAR alpha (retinoic acid receptor), an oncoprotein that has a central role in leukemogenesis.

Apoptosis↗

Interpretative views on Hispanics' perinatal problems of low birth weight and prenatal care.

From a public health perspective, there is a need to recognize that Hispanics, and in particular Mexican Americans, are a very heterogeneous group. They represent all shades of acculturation, education, income, and citizenship status. As this minority group continues to increase in numbers, pertinent information about their perinatal health problems in the context of their sociocultural characteristics will be required. This review examines critically the recent literature related to low birth weight and prenatal care and suggests alternative ways to address these perinatal health issues. Low birth weight is examined in the context of the problem of intrauterine growth retardation and the potential mechanisms and consequences of different types of growth limitation in utero which have not been studied in this population. The use of prenatal care by Mexican American women and its association with birth weight is examined as an indication of maternal behavior or as a health care intervention. The implications for public health policy are discussed in relation to the identification, interpretation, and evaluation of these perinatal health issues in this minority population.

Attitude to Health↗