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Biomedical subjects

J L Fan

Publications and source records attributed to J L Fan.

17 recordsLinked to original sources
PubMed1992

Abnormalities in platelets and vascular endothelial cells induced by glycated lipoproteins.

We studied the effects of glycated lipoproteins of low- and high-density (LDL and HDL) on platelets and vascular endothelial cells. After pretreatment for 5 minutes at 37 degrees C, the thrombin-induced synthesis of thromboxane B2 in washed platelets was significantly increased by glycated LDL as compared with native LDL (198.9 +/- 16.2 vs 90.3 +/- 29.4 ng/10(9) platelets, n = 8, p less than 0.01). Platelet aggregation was also increased by glycated LDL as compared with native LDL. After treatment with platelet-rich plasma for 5 hours at 37 degrees C, these values were suppressed by native HDL vs the control (buffer), but not by glycated HDL. Abnormalities in the release of 6-keto prostaglandin F1 alpha and lactate dehydrogenase from vascular endothelial cells were also induced by glycated LDL and/or HDL. These observations suggest that abnormalities induced in platelets and vascular endothelial cells by glycated lipoproteins may play an important role in the development of atherosclerosis in patients with diabetes mellitus.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

[Establishment of the vascular intimal model in vitro and its application in studying atherosclerosis].

An endothelial culture model in vitro mimicking the vascular intima in vivo was designed which was composed of an upper and a lower well separated by a layer of amnion membrane, and upon which endothelial cells (ECs) isolated from the human umbilical vein were cultured. The upper well, the subendothelial amnion, and the lower well were analogical to the vascular lumen, the subendothelial tissue and the extravascular space, respectively. In comparison with the ECs cultured on the plastic, dishes, ECs cultured on the amnion membrane maintained more morphologic features as in vivo and could be cultured for up to 15 days without apparent detachment. Monocytes, loaded in the upper wells, were able to adhere to the cytoplasmic membrane of ECs. Furthermore, with the presence of the chemotactic factor (fMLP) in the lower well, monocytes showed active migrating ability passing through the EC junctions. If LDL (100 micrograms/ml) was added in the media simultaneously, monocytes might be aggregated beneath the subendothelial space and some of them took an foamy appearance. In conclusion, the culture model is of value in the study of experimental inflammation and atherosclerosis.

Amnion↗
PubMed1991

Alterations in the functional characteristics of macrophages induced by hypercholesterolemia.

Intimal accumulation of monocyte-derived lipid-filled macrophages is an important early event in diet-induced hypercholesterolemia. To better understand the functional alterations in macrophages in hypercholesterolemia, we determined several variables in rat peritoneal macrophages putatively associated with atherogenesis including adhesion to, spreading and locomotion on an endothelial monolayer, migration and phagocytic capacities, and superoxide anion (O2-) production. Compared with macrophages from normal rats (NM0s), macrophages from hypercholesterolemic rats (HM0s) revealed a higher rate of adherence to endothelial cells (ECs) and plastic with more extensive cytoplasmic spreading. Towards a chemoattractant of zymosan-activated serum, HM0s exhibited greater chemotactic migration and more prominent aggregation than NM0s. A computerized film analysis using time-lapse cinemicrophotography disclosed that HM0s moved faster on ECs; the average speed of HM0s was almost twice that of NM0s. HM0 phagocytic activity of fluorescent latex beads was significantly heightened (P less than 0.01). By contrast, there was no significant difference in O2- production between the two groups. These results indicate that hypercholesterolemia may initiate and accelerate the atherosclerotic process, at least in part, by modifying a number of functional properties of macrophages.

Animals↗
PubMed1991

Age-related decline in prostacyclin synthesis by human aortic endothelial cells. Qualitative and quantitative analysis.

To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined. The endothelial cells of human aortas and umbilical veins or inferior vena cavae were immunohistochemically examined and found positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. In addition to the endothelial cells, smooth muscle cells in the thickened intima, not the media, of the aorta were also immunoreactive. Endothelial cells were successfully cultured from human aortas obtained from infants through aged subjects and were subdivided into three groups: young, middle, and old. Prostacyclin synthesis by endothelial cells from all types of blood vessels was extremely great at the primary culture, but decreased abruptly in the following subcultures. Among the aortic endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. The in vitro prostacyclin biosynthesis was supported by the qualitative analysis on the tissue sections. These results indicate that prostacyclin synthesis of the aortic endothelial cells decreases with age, but intimal smooth muscle cells potentially have a back-up mechanism and substitute this synthesis to some extent. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Combined treatment of autoimmune MRL/Mp-lpr/lpr mice with cholera toxin plus irradiation. Combined treatment of autoimmune MRL/l mice.

MRL/Mp-lpr/lpr (MRL/1) mice spontaneously develop autoimmune diseases like systemic lupus erythematosus (SLE) from 2 months of age, accompanied by massive lymphadenopathy. Such mice of 2 months of age were treated with 1 microgram cholera toxin (CT) every 7 days and/or with 400 rad of one-shot 60Co irradiation. CT treatment alone markedly improved nephritis as evaluated by proteinuria and moderately suppressed lymphadenopathy and anti-DNA antibody production, while irradiation alone prominently improved lymphadenopathy but showed little effect on both nephritis and anti-DNA antibody production. On the other hand, when mice were treated with the combination of CT plus irradiation, autoimmune nephritis as well as anti-DNA production and lymphadenopathy were almost completely inhibited. Taken together, each agent exerts the improvement effect at the different points from each other in an abnormal immunological circuit displayed in MRL/1 mice. This kind of combined treatment may be applicable to the clinical use for autoimmune diseases.

Animals↗
PubMed1989

Atherosclerosis and macrophages.

Atherosclerosis is undoubtedly a disease of many facets and in this review we have merely touched one angle of this issue. The best-established cause of the disease is hypercholesterolemia. Since the important role of macrophages in lipoprotein metabolism has been confirmed, current interest is focused on the role of macrophages in atherosclerosis. The origin and tissue distribution of foam cells have been discussed in detail, because they are the principal cells in the earliest lesions, the so-called fatty streaks. Once thought to be derived exclusively from smooth muscle cells, foam cells are now known to originate largely from monocytes that enter the intima and become transformed into macrophages. Exactly how monocytes are recruited and retained in the artery wall is not fully understood, but it is certain that the initial event involves adhesion to the endothelial surface followed by penetration under the influence of a chemotactic factor(s). Hypercholesterolemia contributes much to this phenomenon by affecting both monocyte-macrophages and endothelial cells. Intensive current research is increasing our understanding of the dynamic interaction between macrophages and both lipoproteins and vascular cells, and its immediate relevance to lesion formation. Closer scrutiny of the biology and molecular mechanism of the process of atherosclerosis may ultimately permit intervention in and slowing of the progress of this catastrophic human disease using new modalities.

Arteriosclerosis↗
PubMed1989

Atherosclerosis and endothelium. Part II. Properties of aortic endothelial and smooth muscle cells cultured at various ambient pressures.

Human aortic endothelial cells and smooth muscle cells (SMCs) were cultured at various ambient pressures and their properties were examined. The following results were obtained. 1) Endothelial cells were damaged when cultured at higher ambient pressures of 80 and 160 mmHg. This left cellular islands with central confluence showing no evident growth because of strong contact inhibition. 2) Aortic endothelial cells released high levels of prostacyclin, with significantly elevated release at higher ambient pressures, while intimal SMCs released a small amount of prostacyclin, and medial SMCs a minimal amount. 3) Prostacyclin release by aortic endothelial cells was inhibited in the presence of low concentrations of linoleic acid hydroperoxide (LAHO). Intimal and medial SMCs, however, showed no LAHO inhibition. These results indicate that the properties of both endothelial cells and SMCs vary according to in vitro and probably in vivo conditions. Their specific roles in the pathogenesis of various vascular disorders including atherosclerosis should be carefully considered.

Aorta↗
PubMed1989

HLA serologic epitopes.

A total of 25,000 antisera from parous women was evaluated for antibody specificity toward HLA epitopes in the A,B, and C loci. It was determined that most of the reactivity patterns against a large panel could be accounted for by the amino acid substitutions at the known residues. It has been surprising that each of the variable amino acids at each residue against which antisera have been found belonged on either the A, B, or C locus.

Amino Acid Sequence↗
PubMed1989

Atherosclerosis- and age-related multinucleated variant endothelial cells in primary culture from human aorta.

Endothelial cells were cultured from human aortas and inferior venae cavae of autopsied subjects ranging in age from infancy to 85 years. Endothelial cells in 32 of more than 100 attempted cultures were pure enough for evaluation. Emerged endothelial cells in primary culture were classified into two types: typical endothelium and variant endothelium. Typical endothelial cells were small, round to polygonal shaped, and were arranged uniformly. Their diameter ranged from 50 to 70 microns. Variant endothelial cells were larger, ranging from 100 to 200 microns in diameter, and giant endothelial cells measuring more than 250 microns in diameter were scattered among them. Variant endothelial cells were usually multinucleated and possessed endothelium-specific markers of vWF and Weibel-Palade bodies. No incorporation of [3H]thymidine was found in the nuclei of cultured variant endothelial cells. Although most cultured endothelial cells were of the typical type, variant endothelial cells were interspersed throughout the culture. The ratio of variant endothelial cells to typical cells correlated well with the severity of atherosclerosis, but less so with aging. The number of variant endothelial cells in cultures from inferior venae cavae was slight and constant throughout all age groups. The presence of multinucleated endothelial cells in in vivo aortas was confirmed by both scanning and transmission electron microscopy. They sometimes existed in colonies in the aortas from elderly subjects with intimal-thickened or advanced atherosclerotic lesions. These results indicate that variant endothelial cells were present in vivo and their ratio in primary culture reflected the in vivo population. It is likely that these cells were formed by adhesion of adjacent typical endothelial cells and that this process was affected more by atherosclerosis than by aging. Although it is not clear if the multinucleated variant cells were formed before the formation of atherosclerotic plaque or after the plaque formation, they will contribute to further development of atherosclerotic lesions, which in turn cause malfunction of the cell membrane. We suggest that there is a cyclic effect of these processes for multiplication of the variant endothelial cells and advancement of atherosclerotic lesions.

Adolescent↗
PubMed1988

Drug-induced in vitro tolerance to allogeneic antigens. II. Further analysis of in vitro-tolerized spleen cells in a fully allogeneic murine combination.

C3H/HeSlc (C3H, H-2k) spleen cells were made tolerant in vitro to C57BL/6CrSlc (B6, H-2b) at the cell-mediated cytotoxicity (CMC) level by in vitro stimulation for 48 hr with mitomycin C (MMC)-treated B6 spleen cells, and treatment with 5 micrograms/ml of 5-fluorouracil for a further 9 hr. These cells were given intraperitoneally to neonate (C3HxB6) F1 mice to examine whether these tolerized spleen cells would cause lethal graft-versus-host disease (GVHD). Despite the lack of CMC, the tolerized C3H spleen cells caused lethal GVHD in most of the neonate F1 mice. Evaluating from various immune parameters, it was evident that T cell populations responsible for IL-2 production, cytostasis, and delayed footpad reaction (DFR) were retained intact after in vitro tolerance induction, probably because of their less-proliferative characteristics in response to fully allogeneic antigen stimulation, and were considered to be responsible for lethal GVHD. Contribution of natural killer (NK) cells to lethal GVHD was not ruled out.

Animals↗
PubMed1987

Drug-induced tolerance to allografts in mice. X. Augmentation of split tolerance in murine combinations disparate at both H-2 and non-H-2 antigens by the use of spleen cells from donors preimmunized with recipient antigens.

In a fully allogeneic murine combination of C3H/HeSlc (C3H) (H-2k) and C57BL/6CrSlc (B6) (H-2b), C3H mice were primed i.v. with 1 X 10(8) spleen cells from B6 mice preimmunized i.v. with 5 X 10(7) C3H spleen cells and then were given i.p. 200 mg/kg cyclophosphamide (CP) 2 days later (Im-B6-Sc plus CP group). The tolerant state in those recipient mice was compared with that in mice made tolerant conventionally with 1 X 10(8) naive B6 spleen cells plus 200 mg/kg CP (naive-B6-Sc plus CP group). B6 skin was rejected in an almost normal fashion in both the naive-B6-Sc plus CP group and the Im-B6-Sc plus CP group. However, EL4 tumor allografts (B6 origin) inoculated after complete rejection of B6 skin grafts were specifically accepted in both groups. Moreover, the tumor growth in the Im-B6-Sc plus CP group was faster than that in the naive-B6-Sc plus CP group. Mixed lymphocyte reaction, cytotoxic T lymphocyte activity, and antibody production against the tolerogen were depressed more profoundly in the Im-B6-Sc plus CP group than in the naive-B6-Sc plus CP group. These observations were consistent with the results from tumor allografting. The other immunological parameters examined in the present study, including helper T cell activity and delayed foot-pad reaction, were retained in the Im-B6-Sc plus CP group at the same levels as in the naive-B6-Sc plus CP group. These observations were consistent with the results from skin allografting. In conclusion, tumor allograft tolerance was made more profound by the use of spleen cells from donors preimmunized with recipient antigens as the tolerogen than by the use of naive spleen cells. However, skin allograft tolerance was not achieved at all by these same treatments. The contribution of graft-versus-host disease to this phenomenon was excluded by the chimeric analysis in AKR/JSea (H-2k) mice given the preimmunized (with AKR antigens) B6 spleen cells plus CP. These results strongly support the existence of a less proliferative lymphocyte population which does not evoke cell divisions to mature even after the strong stimulation with the preimmunized spleen cells and is resistant to tolerance induction.

Animals↗
PubMed1987

Drug-induced tolerance to allografts in mice. XII. The relationships between tolerance, chimerism, and graft-versus-host disease.

When AKR/J Sea (AKR, H-2k) mice were primed i.v. with 1 X 10(8) viable spleen cells from naive C3H/He Slc (C3H, H-2k) mice and treated i.p. with 200 mg/kg cyclophosphamide (CP) 2 days later, a minimal degree of mixed chimerism associated with tolerance to C3H skin was established without graft-versus-host disease (GVHD) and maintained for at least one month. When AKR mice were primed i.v. with 1 X 10(8) viable spleen cells from C3H mice preimmunized i.v. 7 days earlier with 5 X 10(7) viable AKR spleen cells, and treated with 200 mg/kg CP, chimerism became exclusive, but lethal GVHD occurred in the AKR mice. Moreover, most of normal AKR mice primed with the preimmunized C3H spleen cells without CP died of GVHD. In contrast, in a major histocompatibility complex (MHC)-incompatible combination of AKR (H-2k)-C57BL/6 Cr Slc (B6, H-2b), mixed chimerism, tolerance to skin allografts, and GVHD were not observed, whether or not the mice had been treated with naive or preimmunized B6 spleen cells with or without CP.

Animals↗
PubMed1987

Treatment of autoimmune MRL/Mp-lpr/lpr mice with cholera toxin.

The autoimmune manifestations of MRL/Mp-lpr/lpr(MRL/l), a murine model of systemic lupus erythematosus (SLE), were alleviated by administering 1 microgram cholera toxin (CT) every 14 days. The beneficial effects were: (i) significant prolongation of survival time, (ii) prevention of lymphadenopathy, (iii) improvement of T cell mitogenic responses and suppression of a B cell mitogenic response, (iv) decrease in serum anti-DNA and anti-Sm antibodies, (v) increase in IL-2 production by stimulation of spleen cells with concanavalin A (Con A). It is possible that CT may be effective for treatment of murine lupus nephritis by modulating polyclonal lymphocyte activation. This type of immunomodulation may pave the way toward treatment of lupus and other autoimmune diseases.

Animals↗
PubMed1986

Drug-induced tolerance to allografts in mice. IX. Establishment of complete chimerism by allogeneic spleen cell transplantation from donors made tolerant to H-2-identical recipients.

Graft-versus-host reaction (GVH) after allogeneic spleen cell transplantation was completely suppressed in an H-2-matched murine combination (AKR/J Sea [H-2k]----lethally irradiated C3H/He Slc [H-2k]) by pretreatment of the donors with recipient spleen cell antigen plus cyclophosphamide (CP). Irradiated recipients receiving cells became chimeric. In contrast to the H-2 matched combination, lethal GVH reaction could not be prevented in an H-2-mismatched fully allogeneic combination (C57BL/6 Cr Slc [H-2b]----lethally irradiated C3H/He Slc [H-2k]) by pretreatment of the donors. The results suggest that the effectors responsible for the GVH reaction were abrogated by pretreatment of the donors with allogeneic recipient spleen cells plus CP in the H-2-matched combination, but donor pretreatment failed to abrogate GVH reaction in the H-2-mismatched combination.

Animals↗