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Biomedical subjects

J Jiang

Publications and source records attributed to J Jiang.

At least 343 records · Page 19Linked to original sources
PubMed1996

Intimal thickening develops without humoral immunity in a mouse aortic allograft model of chronic vascular rejection.

BACKGROUND: The major threat to the long-term survival of cardiac allograft recipients is the development of diffuse intimal thickening in the allograft coronary arteries through mechanisms that are poorly understood. Although antidonor antibodies have been associated with the development of this condition, a causal relationship has not been established. METHODS AND RESULTS: To determine whether humoral immune responses are necessary for the development of graft vascular disease, we performed abdominal aortic allografts from normal donor mice into different immunodeficient recipient mice: those lacking all donor-specific immune responses (severe combined immunodeficient [SCID] mice and recombination activating gene-1 [RAG-1]-deficient mice) and those lacking humoral immune responses alone owing to a targeted deletion of the joining region (JH) gene segments for the immunoglobulin heavy chain. At 6 to 9 weeks after transplantation, aortic allografts in normal immunocompetent recipients showed concentric intimal thickening extending the full length of the graft (percent luminal reduction, [%LR], 31.2 +/- 9.1 [mean +/- SD] and 38.5 +/- 3.6 in different donor-recipient strain combinations). In contrast, syngeneic (histocompatible) aortic grafts showed a normal-appearing vessel wall (%LR, 1.6 +/- 0.7). In both SCID and RAG-1-deficient recipients, aortic allografts showed a virtual absence of neointimal formation (%LR, 3.7 +/- 2.1 and 3.8 +/- 1.6 in SCID and RAG-1-deficient recipients, respectively), indicating a critical etiological role for alloimmune responses in this model. Importantly, allografts in JH-deficient mice showed marked intimal thickening (%LR, 35.7 +/- 7.9), with an appearance histologically indistinguishable from that of normal immunocompetent recipients. CONCLUSIONS: Neointimal formation in graft vascular disease is critically dependent on alloimmune responses of the host. Humoral effector mechanisms, however, may not be required.

Analysis of Variance↗
PubMed1996

Melanotropic peptide-conjugated beads for microscopic visualization and characterization of melanoma melanotropin receptors.

We developed two solid-phase reagent systems for microscopic visualization and characterization of melanocyte-stimulating hormone (MSH) receptors of melanoma cells. Multiple copies of [Nle-4,D-Phe-7]-alpha-MSH, a potent analog of alpha-MSH, were conjugated to microspheres (latex beads) or macrospheres (polyamide beads) through a thioether or disulfide bond. Binding between the beads and mouse and human melanoma cells was examined by scanning electron microscopy and by light microscopy. Each mouse and human melanoma cell (of all cell lines) evinced binding to the beads. Binding of the melanotropin conjugates was not restricted to any one phase of the cell cycle. Specificity of binding was demonstrated by several studies. Negative controls included cell types of nonmelanocyte origin (e.g., mammary cancer cells) and beads that lacked the melanotropic ligand or had other attached ligands. Beads with a disulfide-linked melanotropin analog served as a direct control. Treatment of these beads with DTT during or before incubation of the beads with melanoma cells (resulting in release of the MSH analog from the beads) eliminated binding of the beads to melanoma cells. Binding interactions between melanoma cells and melanotropin-bound beads also could be abolished by prior incubation with unconjugated MSH analog. During these experiments, certain membrane receptor-hormone associated phenomena, such as capping (aggregation) of the receptor-ligand complex, also were observed. These results provide visual evidence that MSH receptors are a property common to melanoma cells. Normal human epidermal melanocytes and keratinocytes were also shown to express melanotropin receptors by the same criteria established for melanoma cells.

Animals↗
PubMed1996

A conserved repetitive DNA element located in the centromeres of cereal chromosomes.

Repetitive DNA sequences have been demonstrated to play an important role for centromere function of eukaryotic chromosomes, including those from fission yeast, Drosophila melanogaster, and humans. Here we report on the isolation of a repetitive DNA element located in the centromeric regions of cereal chromosomes. A 745-bp repetitive DNA clone pSau3A9, was isolated from sorghum (Sorghum bicolor). This DNA element is located in the centromeric regions of all sorghum chromosomes, as demonstrated by fluorescence in situ hybridization. Repetitive DNA sequences homologous to pSau3A9 also are present in the centromeric regions of chromosomes from other cereal species, including rice, maize, wheat, barley, rye, and oats. Probe pSau3A9 also hybridized to the centromeric region of B chromosomes from rye and maize. The repetitive nature and its conservation in distantly related plant species indicate that the pSau3A9 family may be associated with centromere function of cereal chromosomes. The absence of DNA sequences homologous to pSau3A9 in dicot species suggests a faster divergence of centromererelated sequences compared with the telomere-related sequences in plants.

Animals↗
PubMed1996

Interphase fluorescence in situ hybridization mapping: a physical mapping strategy for plant species with large complex genomes.

The chromatin in interphase nuclei is much less condensed than are metaphase chromosomes, making the resolving power of fluorescence in situ hybridization (FISH) two orders of magnitude higher in interphase nuclei than on metaphase chromosomes. In mammalian species it has been demonstrated that within a certain range the interphase distance between two FISH sites can be used to estimate the linear DNA distance between the two probes. The interphase mapping strategy has never been applied in plant species, mainly because of the low sensitivity of the FISH technique on plant chromosomes. Using a CCD (charge-coupled device) camera system, we demonstrate that DNA probes in the 4 to 8 kb range can be detected on both metaphase and interphase chromosomes in maize. DNA probes pA1-Lc and pSh2.5.SstISalI, which contain the maize loci a1 and sh2, respectively, and are separated by 140 kb, completely overlapped on metaphase chromosomes. However, when the two probes were mapped in interphase nuclei, the FISH signals were well separated from each other in 86% of the FISH sites analyzed. The average interphase distance between the two probes was 0.50 micron. This result suggests that the resolving power of interphase FISH mapping in plant species can be as little as 100 kb. We also mapped the interphase locations of another pair of probes, ksu3/4 and ksu16, which span the Rp1 complex controlling rust resistance of maize. Probes ksu3/4 and ksu16 were mapped genetically approximately 4 cM apart and their FISH signals were also overlapped on metaphase chromosomes. These two probes were separated by an average of 2.32 microns in interphase nuclei. The possibility of estimating the linear DNA distance between ksu3/4 and ksu16 is discussed.

Cell Nucleus↗
PubMed1996

Influence of macrophage depletion on bacterial translocation and rejection in small bowel transplantation.

Rejection and sepsis can be intimately related following small bowel transplantation when rejection compromises normal intestinal barrier mechanisms and bacterial translocation results. Macrophages play a role in controlling the egress of intestinal luminal bacteria--and they have also been implicated in allograft rejection. In this study, the role of macrophages in rejection and bacterial translocation was evaluated by depleting macrophages in donors and/or recipients of rat small bowel allografts with injection of liposome-encapsulated dichloromethylene diphosphonate (CL2MDP). In preliminary studies, we demonstrated that a single intraperitoneal injection of liposome-encapsulated CL2MDP (350 mg/kg) depleted ED2-positive macrophages by > 90% in the liver mesenteric lymph nodes and proximal and distal small bowel, and by approximately 50% in the spleen. ED1-positive macrophages were depleted by > 90% in the liver and by approximately 50% at the other sites. ED3-positive macrophages were completely depleted. Dendritic cells were > 90% depleted in the spleen and mesenteric lymph nodes, but were not depleted in the small bowel. Macrophage depletion in the donor resulted in increased translocation of bacteria to the peritoneal cavity (P = 0.03) if recipient macrophages were present. With histopathologic analysis, a significantly milder rejection with less arteritis was seen in the allografts of the recipient macrophage-depleted group compared with nondepleted controls (P = 0.045). This suggests that recipient macrophages play an important role in rejection. With macrophage depletion in both the donor and the recipient, graft survival was prolonged significantly (13.2 +/- 1.9 days) compared with non-macrophage-depleted controls (9.2 +/- 1.3 days) (P = 0.003). These studies suggest that strategies targeting recipient macrophages may be useful in controlling small bowel allograft rejection without increasing bacterial translocation.

Animals↗
PubMed1996

Complementary and mutually exclusive activities of decapentaplegic and wingless organize axial patterning during Drosophila leg development.

Growth and patterning of the Drosophila leg are organized by three secreted proteins: Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Hh is secreted by posterior cells; it acts at short range to induce dorsal anterior cells to secrete Dpp and ventral anterior cells to secrete Wg. Here we show that the complementary patterns of dpp and wg expression are maintained by mutual repression: Dpp signaling blocks wg transcription, whereas Wg signaling attenuates dpp transcription. We also show that this mutual repression is essential for normal axial patterning because it ensures that the dorsalizing and ventralizing activities of Dpp and Wg are restricted to opposite sides of the leg primordium and meet only at the center of the primordium to distalize the appendage.

Animals↗
PubMed1996

Liver injury model in mice induced by a cellular immunologic mechanism--delayed-type hypersensitivity-induced liver injury to picryl chloride and phenotype of effector cell.

Liver injury was induced in BALB/c mice by local delayed-type hypersensitivity (DTH) to picryl chloride (PC1). Distinct changes of biochemical parameters were observed including the elevation of serum alanine and aspartate aminotransferases, increase of liver lipid peroxides, as well as decrease of serum alkaline phosphatase. Damage was confirmed by histopathological findings such as hepatocellular necrosis, granulocyte infiltration, and fatty degeneration. The liver injury was passively transferred into naive syngeneic mice by infusing spleen cells from immune mice. The capacity of the splenocytes to induce liver injury in recipient mice was almost completely abolished by pretreatment of the cells with anti-Thy 1.2 or anti-CD4, but not anti-CD8 antibody. These findings suggest that the production of liver injury by a local DTH mechanism is possible and the subpopulation of T cells, Thy-1.2+, L3T4+, and Lyt-2- cells, is at least one of the effector cells that mediate the injury.

Animals↗
PubMed1996

Use of nitroxides for assessing perfusion, oxygenation, and viability of tissues: in vivo EPR and MRI studies.

Relative perfusion, pO2, and bioreduction were measured simultaneously in vivo in tissues in mice by following changes in the intensity and shape of the EPR spectra of nitroxides injected directly into the tissues, using low frequency (1.1 GHz) localized EPR spectroscopy. Using normal and blood flow restricted gastrocnemius muscles it was shown that the decrease of the EPR signals of the nitroxides in tissues was due principally to perfusion, which redistributed the nitroxides. Changes in pO2 were reflected by changes of the linewidth; only a perdeuterated nitroxide with a narrow line was an adequate indicator for this parameter. This technique was applied experimental murine tumors (MTG-B and RIF-1) to determine the perfusion and pO2 in these relatively hypoxic model tumor systems. Using the paramagnetic properties of the nitroxides to enhance T1-weighted MR images, heterogeneity in perfusion in individual tumors was demonstrated

Animals↗
PubMed1996

Schistosoma mansoni: the glucose transport protein SGTP4 is present in tegumental multilamellar bodies, discoid bodies, and the surface lipid bilayers.

Schistosomes metabolize large quantities of glucose obtained from the host serum by facilitated diffusion through the tegument. Here we have used rabbit antibodies affinity purified against the carboxyl terminus of a facilitated glucose transporter, SGTP4, to localize the antigen in both schistosomula and adults. By ultrastructural immunocytochemical analysis, SGTP4 was localized to both lipid bilayers that cover the tegumental surface of adults and schistosomula. In the inner bilayer of adults, SGTP4 was apparently oriented with the carboxyl terminus on the internal side of the bilayer. SGTP4 was also present in the discoid and multilamellar bodies in adults and the membranous bodies in schistosomula. Finally, the affinity purified antibodies against SGTP4 bound nonspecifically to the head glands and postacetabular glands in schistosomula. The localization of the antigen in the two surface lipid bilayers suggests that SGTP4 may be responsible for transporting glucose from mammalian host serum into the tegument.

Amino Acid Sequence↗
PubMed1996

Regulation of glucagon-like peptide-I receptor expression and transcription by the protein kinase C pathway.

Glucagon-like peptide-I (GLP-I) is an important insulinotropic incretin hormone. The GLP-I receptor belongs to the family of seven transmembrane domain receptors. We studied the regulation of its expression by the protein kinase C (PKC)-dependent pathway in rat insulinoma RINm5F cells. Cells were incubated for 3, 6 and 24 h with an optimal concentration of tissue plasminogen activator (TPA), an activator of PKC. TPA induced significantly lower GLP-I receptor mRNA levels under steady-state conditions after 6 and 24 h. The stability of the GLP-I receptor mRNA was unchanged. The number of GLP-I receptors present on RINm5F cells was reduced after 6 and 24 h. TPA did not influence the affinity of remaining receptors to its specific ligand. These data indicate that PKC activation downregulates the expression of the GLP-I receptor gene, mainly at the transcriptional level.

Animals↗
PubMed1996

Population toxicokinetics of tetrachloroethylene.

In assessing the distribution and metabolism of toxic compounds in the body, measurements are not always feasible for ethical or technical reasons. Computer modeling offers a reasonable alternative, but the variability and complexity of biological systems pose unique challenges in model building and adjustment. Recent tools from population pharmacokinetics, Bayesian statistical inference, and physiological modeling can be brought together to solve these problems. As an example, we modeled the distribution and metabolism of tetrachloroethylene (PERC) in humans. We derive statistical distributions for the parameters of a physiological model of PERC, on the basis of data from Monster et al. (1979). The model adequately fits both prior physiological information and experimental data. An estimate of the relationship between PERC exposure and fraction metabolized is obtained. Our median population estimate for the fraction of inhaled tetrachloroethylene that is metabolized, at exposure levels exceeding current occupational standards, is 1.5% [95% confidence interval (0.52%, 4.1%)]. At levels approaching ambient inhalation exposure (0.001 ppm), the median estimate of the fraction metabolized is much higher, at 36% [95% confidence interval (15%, 58%)]. This disproportionality should be taken into account when deriving safe exposure limits for tetrachloroethylene and deserves to be verified by further experiments.

Administration, Inhalation↗
PubMed1996

Toxigenic molds in water-damaged buildings: dechlorogriseofulvins from Memnoniella echinata.

An investigation of a cluster of cases of pulmonary hemosiderosis in infants in Cleveland, OH, led to the isolation of many isolates of Stachybotrys atra and two isolates of a related toxigenic fungus, Memnoniella echinata. M. echinata produces two cytotoxic trichothecene mycotoxins, trichodermol (1a) and trichodermin (1b), as well as several griseofulvins. Dechlorogriseofulvin (2a) and epidechlorogriseofulvin (2b) were the major compounds isolated. This is the first report of a fungus outside the Penicillium genus producing griseofulvins.

Griseofulvin↗
PubMed1996

Ligand-induced regulation of glucagon-like peptide-I receptor function and expression in insulin-secreting beta cells.

Glucagon-like peptide-I (GLP-I) is a potent incretin hormone and mediates its actions via the cyclic AMP (cAMP) pathway. The GLP-I receptor belongs to the family of seven-transmembrane domain receptors coupled to G proteins. We have analyzed the regulation of GLP-I receptor function and expression by its own ligand and the cAMP-dependent pathway in rat insulinoma-derived beta cells (RINm5F). The GLP-I receptor underwent rapid homologous desensitization, which occurred at the receptor level. This was characterized by a reduced binding capacity not mediated by protein kinase A (PKA). GLP-I receptor mRNA levels were down-regulated during incubation of cells by agents increasing cAMP levels including GLP-I itself. This effect was dependent upon time and concentration. Forskolin, the PKA activator 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole-3, 5-monophosphorothiotate, and GLP-I stabilized the GLP-I receptor mRNA. All induced down-regulation of the GLP-I receptor number within 3 h, a time point at which GLP-I receptor mRNA levels were not decreased. This effect was not influenced by cycloheximide. Therefore, in addition to transcriptional effects, posttranslational mechanisms exist to regulate GLP-I receptor numbers in insulin-secreting cells.

Animals↗