Assignment of the SIAT4A gene to bovine chromosome 14 by linkage mapping of an associated microsatellite.
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Biomedical subjects
Publications and source records attributed to C Li.
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Stress-associated immune responses were compared between young (8 weeks of age) and old (56 weeks) mice. Since stress suppresses the conventional immune system (i.e. T and B cells) but inversely activates the primordial immune system (i.e. extrathymic T cells, NKT cells, and granulocytes), these parameters were analysed after restraint stress for 24 h. The thymus became atrophic as a function of age, and an age-related increase in the number of lymphocytes was seen in the liver. Although the number of lymphocytes in both the thymus and liver decreased as the result of stress, the magnitude was much more prominent in the thymus. To determine stress-resistant lymphocyte subsets, two-colour immunofluorescence tests were conducted in the liver and spleen. NKT cells were found to be such cells in the liver of young mice. On the other hand, an infiltration of granulocytes due to stress was more prominent in the liver of old mice than in young mice. Liver injury as a result of stress was prominent in young mice. This age-related bias in the function of NKT cells and granulocytes seemed to be associated with a difference in the responses of catecholamines (high in old mice) and corticosterone (high in young mice) after stress. Indeed, an injection of adrenaline mainly induced the infiltration of granulocytes while that of cortisol activated NKT cells. The present results suggest the existence of age-related bias in the function of NKT cells and granulocytes after stress and that such bias might be produced by different responses of sympathetic nerves and steroid hormones between young and old mice.
PROBLEM: Urokinase and streptokinase are commonly used thrombolytic agents for obstructed central venous catheters. Although proven to be efficacious, these agents have the potential to induce fibrin breakdown and streptokinase cannot be used repeatedly because of its allergenic nature. Published evidence suggests that Urokinase is safe and effective (>70% efficacy for catheter installation) and that Tissue-type plasminogen activator (rt-PA) can achieve as much as 98% success. OBJECTIVE: To describe our experience with and our protocol for the use of rt-PA as an alternative agent for catheter thrombolysis. DESIGN: Investigation of a cohort of haemodialysis patients with tunnelled central venous catheter (SPCVC) placed between December 2001 to August 2003 and who developed catheter thrombus (female, n = 8: male, n = 12). Each patient was given an infusion of between 1 and 2 mg rt-PA/h for 4 h. The dose was dependent on partial or total line obstruction. The technical success of rt-PA is defined as returning catheter blood flow to >250 mL/min for a 4-h period. FINDINGS: Twenty patients required 57 infusions in 38 lumens between 01/01/02 to 01/09/03. For completely blocked lines rt-PA was infused at 2 mg/h for 4 h achieving 85% success rate. For inadequate flow (<250 mL/min) rt-PA was infused at 1 mg/h for 4 h achieving an 88% success rate. CONCLUSION: Rt-PA administered at 2 mg/h for blocked lines effectively restores haemodialysis catheter patency, and at 1 mg/h for sluggish lines is also effective in restoring blood flow through catheters.
Quantitative trait loci for growth traits in beef cattle have been previously reported and fine-mapped in three chromosomal regions of 0 to 30 cM, 55 to 70 cM, and 70 to 80 cM of bovine chromosome 5. In this study, we further examined the association between gene-specific single nucleotide polymorphisms (SNP) of two positional candidate genes, bovine myogenic factor 5 (myf5) and insulin-like growth factor-1 (igf1), in the QTL regions and the birth weight (BWT), preweaning average daily gain (PWADG), and average daily gain on feed (ADGF) in commercial lines of Bos taurus. The QTL regions for the growth traits identified using a haplotype association analysis, which included the gene-specific SNP markers for both genes in this study, were in agreement with previous studies. The gene-specific SNP marker association analysis indicated that the SNP in myf5 had a significant additive effect on PWADG in the M1 line of Beefbooster Inc. (P < 0.10), and a significant additive effect (P < 0.05) and a significant dominance effect (P < 0.10) on ADGF in the M3 line of Beefbooster Inc. When the data from the two commercial lines were pooled, the SNP in myf5 showed a significant association with PWADG (P < 0.10) and with ADGF (P < 0.05). The association between the SNP and BWT, however, did not reach a significance level in the M1 line, the M3 line, or across the lines. For igf1, no significant association between the SNP and the growth traits was detected in either the M1 line or the M3 line, whereas there was only a significant dominance effect (P < 0.10) on BWT detected for the SNP in igfl when the data from the two commercial lines were pooled. These results suggest that myf5 is a strong candidate gene that influences PWADG and ADGF in beef cattle. The SNP of igf1 may not be a causative or close to the causative mutation that affects the three growth traits in the populations of beef cattle examined in this study. Other SNP of igf1 and myf5 or other genes in their respective chromosomal regions, however, should also be studied.
We report the identification and fine mapping of QTL for birth weight (BWT), preweaning ADG (PWADG), and postweaning ADG on feed (ADGF) in a commercial line of Bos taurus using an identical-by-descent haplotype sharing method. One hundred seventy-six calves of 12 bulls (9 to 30 male calves from each sire) of the Beefbooster, Inc., M1 line were typed using 71 genetic markers from bovine chromosomes (BTA) 2, 6, 14, 19, 21, and 23 (8 to 16 markers from each chromosome). Sixteen haplotypes were found to have significant (P <0.05) associations with BWT at the comparison-wise threshold. The 16 haplotypes span 13 chromosomal regions, two on BTA 2 (9.1 to 22.5 cM and 95.0 to 100.3 cM), three on BTA 6 (8.2 to 11.8 cM, 35.5 to 49.7 cM, and 83.0 to 86.2 cM), three on BTA 14 (26.0 to 26.7 cM, 36.2 to 46.2 cM, and 52.0 to 67.7 cM), one on BTA 19 (52.0 to 52.7 cM), two on BTA 21 (9.9 to 20.4 cM and 28.2 to 46.1 cM), and two on BTA 23 (23.9 to 36.0 cM and 45.1 to 50.9 cM). Thirteen haplotypes spanning seven chromosomal regions significantly affected (P <0.05) PWADG at the comparison-wise threshold. The seven chromosomal regions include two regions on BTA 6 (11.8 to 44.2 cM and 83.0 to 86.2 cM), one on BTA 14 (26.7 to 50.8 cM), one on BTA 19 (4.8 to 15.9 cM), one on BTA 21 (9.9 to 20.4 cM), and two on BTA 23 (17.3 to 36.0 cM and 45.1 to 50.9 cM). For ADGF, 11 haplotypes were identified to have significant associations (P <0.05) at the comparison-wise threshold. The 11 haplotypes represented eight chromosomal regions, one on BTA 2 (9.1 to 22.5 cM), two on BTA 6 (49.7 to 50.1 cM and 59.6 to 63.6 cM), two on BTA 14 (17.0 to 24.0 cM and 36.2 to 46.2 cM), two on BTA 19 (52.0 to 52.7 cM and 65.1 to 65.7 cM), and one on BTA 21 (46.1 to 53.1 cM). The QTL regions identified and fine mapped in this study will provide a reference for future positional candidate gene research and marker-assisted selection of various growth traits.
Backfat thickness is one of the major quantitative traits that affects carcass quality in beef cattle. In this study, we identified and fine-mapped QTL for backfat EBV on bovine chromosomes 2, 5, 6, 19, 21, and 23 using an identical-by-descent haplotype-sharing analysis in a commercial line of Bos taurus. Eleven haplotypes were found to have significant associations with backfat EBV at the comparison-wise P-value threshold, and one at the chromosome-wise P-value threshold on bovine chromosomes 5, 6, 19, 21, and 23. On average, the 12 significant haplotypes had an effect of 0.62 SD on backfat EBV, ranging from 0.38 SD to 1.33 SD. The 12 significant haplotypes spanned nine chromosomal regions, one on chromosome 5 (65.4 to 70.0 cM), three on 6 (8.2 to 11.8 cM, 63.6 to 68.1 cM, and 81.5 to 83.0 cM), three on 19 (4.8 to 15.9 cM, 39.4 to 46.5 cM, and 65.7 to 99.5 cM), one on 21 (46.1 to 53.1 cM), and one on 23 (45.1 to 50.9 cM). Among the nine chromosomal regions, six were new QTL regions and three showed remarkable agreement with QTL regions that were previously reported. Eight of the nine QTL regions were localized to less than or close to 10 cM in genetic distance. The results provide a useful reference for further positional candidate gene research and marker-assisted selection for backfat.
Residual feed intake (RFI) has been proposed as an index for determining beef cattle energetic efficiency. Although the relationship of RFI with feed conversion ratio (FCR) is well established, little is known about how RFI compares to other measures of efficiency. This study examined the phenotypic relationships among different measures of energetic efficiency with growth, feed intake, and ultrasound and carcass merit of hybrid cattle (n = 150). Dry matter intake, ME intake (MEI), ADG, metabolic weight (MWT), and FCR during the test averaged 10.29 kg/d (SD = 1.62), 1,185.45 kJ/(kg0.75 x d) (SD = 114.69), 1.42 kg/d (SD = 0.25), 86.67 kg0.75 (SD = 10.21), and 7.27 kg of DM/kg of gain (SD = 1.00), respectively. Residual feed intake averaged 0.00 kg/d and ranged from -2.25 kg/d (most efficient) to 2.61 kg/d (least efficient). Dry matter intake (r = 0.75), MEI (r = 0.83), and FCR (r = 0.62) were correlated with RFI (P < 0.001) and were higher for animals with high (>0.5 SD) RFI vs. those with medium (+/-0.5 SD) or low (<0.5 SD) RFI (P < 0.001). Partial efficiency of growth (PEG; energetic efficiency for ADG) was correlated with RFI (r = -0.89, P < 0.001) and was lower (P < 0.001) for high- vs. medium- or low-RFI animals. However, RFI was not related to ADG (r = -0.03), MWT (r = -0.02), relative growth rate (RGR; growth relative to instantaneous body size; r = -0.04), or Kleiber ratio (KR; ADG per unit of MWT; r = -0.004). Also, DMI was correlated (P < 0.01) with ADG (r = 0.66), MWT (r = 0.49), FCR (r = 0.49), PEG (r = -0.52), RGR (r = 0.18), and KR (r = 0.36). Additionally, FCR was correlated (P < 0.001) with ADG (r = -0.63), PEG (r = -0.83), RGR (r = -0.75), and KR (r = -0.73), but not with MWT (r = 0.07). Correlations of measures of efficiency with ultrasound or carcass traits generally were not different from zero except for correlations of RFI, FCR, and PEG, respectively, with backfat gain (r = 0.30, 0.20, and -0.30), ultrasound backfat (r = 0.19, 0.21, and -0.25), grade fat (r = 0.25, 0.19, and -0.27), lean meat yield (r = -0.22, -0.18, and 0.24), and yield grade (r = 0.28, 0.24, and -0.25). These phenotypic relationships indicate that, compared with other measures of energetic efficiency, RFI should have a greater potential to improve overall production efficiency and PEG above maintenance, and lead to minimal correlated changes in carcass merit without altering the growth and body size of different animals.
The aim of our study was to evaluate the diagnostic sensitivity of the new thyrotropin receptor antibody (TRAb) assays (Cosmic TRAb CT, ELISA and Yamasa DYNOtest TRAb). TRAb was positive in 43 of 44 (97.7%) untreated patients with Graves' disease by both TRAb CT and/or ELISA and NYNOtest TRAb. Thus the new TRAb assays were clearly more sensitive than the conventional assay (positivity: 85%). There was a strong positive correlation between the data obtained in TRAb CT and/or ELISA and those obtained in DYNOtest TRAb (r = 0.942, p < 0.0001). There was a significant correlation between the new TRAb and TSAb (r = 0.696, p < 0.0001). Although there was a significant correlation between the new TRAb and thyroid stimulation-blocking antibody (TSBAb), the correlation coefficient was low (r = 0.605, p < 0.0001). The increased sensitivity of the new TRAb assays for Graves' disease provides an advantage over conventional assay.
Vascular endothelial growth factor-C (VEGF-C) and VEGF-D are members of the VEGF family of cytokines and have angiogenic and lymphangiogenic actions. In gastric adenocarcinoma, VEGF-C mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis and in some reports, venous invasion and reduced 5-year survival. Patients with gastric adenocarcinomas containing high levels of VEGF-C expression have significantly reduced 5-year survival rates, and VEGF-C expression is an independent prognostic risk factor for death. The role of VEGF-C in oesophageal squamous and colorectal cancer and VEGF-D in colorectal cancer is not clear, with conflicting reports in the published literature. In order to exploit potential therapeutic applications, further research is necessary to define the precise roles of these cytokines in health and disease.
We describe the first association of pulmonary atresia, intact ventricular septum, and absent central pulmonary arteries with deletion 22q11.2. The pulmonary blood flow was derived from major aortopulmonary collaterals. The role of the deletion in pulmonary arborization is discussed.
CD105 and its ligand transforming growth factor beta (TGFbeta) are modulators of angiogenesis, which drives tumour growth and metastasis. Tumour microvessel density (MVD) has proven to be an important determinant of prognosis. In this study, we have examined the prognostic value of MVD identified using Mabs to the pan-endothelial marker CD34 and to CD105 in 111 patients with colorectal cancer. The Mab to CD105 preferentially reacts with angiogenic endothelial cells. Of the 111 patients studied, 38 were alive and 73 had died of the disease. The median MVD values counted using anti-CD34 and anti-CD105 were 5 (range 1.40-9.00) and 3.10 (range 0.90-8.00), respectively. Kaplan-Meier survival analysis revealed that only MVD values obtained using CD105 Mab correlated with survival. Patients with a high MVD, above the median (3.10), showed the worst prognosis. A similar outcome was observed when MVD was divided into quartiles. In order to ascertain if this strong expression of CD105 in the tumour vasculature is reflected in patients' plasma, circulating levels of CD105, TGFbeta1 and TGFbeta3 together with the receptor-ligand complexes were quantified in patients with colorectal carcinoma and normal controls. Results showed that except for TGFbeta1, the levels of all other molecules were significantly elevated compared with controls. The levels of CD105 were positively correlated with Dukes' stages. A lower TGFbeta1 level was noted in patients with carcinoma over the controls. Furthermore, TGFbeta3 and CD105/TGFbeta3 complexes were markedly lowered in postoperative compared with preoperative plasma samples. Immunostaining revealed that TGFbeta1 was expressed in cancer cells but TGFbeta3 in the stromal cells, whereas CD105 was exclusively expressed in vascular endothelial cells of tumour blood vessels. In conclusion, this study demonstrates that MVD quantified using a Mab to CD105 is an independent prognostic parameter for survival of patients with colorectal cancer, and that plasma levels of CD105, TGFbeta1, TGFbeta3 and CD105/TGFbeta complexes may be useful markers for assessing disease progression. These data have led us to propose that quantification of these determinants may prove useful to monitor therapeutic efficacy in patients with colorectal cancer, especially those who are being treated with antiangiogenic therapies.
The behavior of vulnerable atherosclerotic plaques is believed to be closely related to plaque composition. There is a need for an effective in vivo technique for examining plaque constituent properties. In this study, Fourier transform infrared spectroscopy using attenuated total reflectance (FTIR-ATR) was used to assess and analyze the biochemical properties of human atherosclerotic plaques. FTIR spectra clearly revealed prominent spectral features corresponding to plaque constituents of interest: the 2930 cm(-1) and 2850 cm(-1) peaks (indicating the presence of lipids), the 1730 cm(-1) peak (lipid esters), the 1550 cm(-1) and 1650 cm(-1) peaks (fibrous tissues), and the 1100-1000 cm(-1) broad phosphate peak (calcification). Spectral data examined on a qualitative basis correlated well with both gross tissue anatomy and histologic features. Gross spatial mappings of tissue sections of both lipidic and calcified plaques were performed. Spectra from various regions of the plaques demonstrated the evolution of lipid peaks, fibrous tissue peaks, and the phosphate calcification band within the plaques. Histologic analysis corroborated the spectral findings in this study.
Replacement of the carboxylic acid group of prostaglandin (PG) F(2alpha) with a nonacidic moiety, such as hydroxyl, methoxy, or amido, results in compounds with unique pharmacology. Bimatoprost (AGN 192024) is also a pharmacologically novel PGF(2alpha) analog, where the carboxylic acid is replaced by a neutral ethylamide substituent. Bimatoprost potently contracted the feline lung parenchymal preparation (EC(50) value of 35-55 nM) but exhibited no meaningful activity in a variety of PG-sensitive tissue and cell preparations. Its activity seemed unrelated to FP receptor stimulation according to the following evidence. 1) Bimatoprost exhibited no meaningful activity in tissues and cells containing functional FP receptors. 2) Bimatoprost activity in the cat lung parenchyma is not species-specific because its potent activity in this preparation could not be reproduced in cells stably expressing the feline FP receptor. 3) Radioligand binding studies using feline and human recombinant FP receptors exhibited minimal competition versus [(3)H]17-phenyl PGF(2a) for Bimatoprost. 4) Bimatoprost pretreatment did not attenuate PGF(2alpha)-induced Ca(2+) signals in Swiss 3T3 cells. 5) Regional differences were apparent for Bimatoprost but not FP agonist effects in the cat lung. Bimatoprost reduced intraocular pressure in ocular normotensive and hypertensive monkeys over a 0.001 to 0.1% dose range. A single-dose and multiple-dose ocular distribution/metabolism studies using [(3)H]Bimatoprost (0.1%) were performed. Within the globe, bimatoprost concentrations were 10- to 100-fold higher in anterior segment tissues compared with the aqueous humor. Bimatoprost was overwhelmingly the predominant molecular species identified at all time points in ocular tissues, indicating that the intact molecule reduces intraocular pressure.
Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.
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Pedicles and antlers are male deer secondary sexual characters. As such, development of these structures is under the control of androgen hormones. Pedicle growth is caused by increasing and elevated plasma testosterone (T) levels, whereas first antler transformation from a fully formed pedicle occurs when the T levels are decreasing. Castration prior to pedicle initiation abrogates future pedicle and antler formation. Female deer also have the potential to develop pedicles and antlers, but they do not normally express this phenotype due to lack of sufficient androgen stimulation. Previous studies have shown that female white-tailed deer could be readily induced to grow pedicles as well as antlers by singular administration of exogenous androgens (EA), but in red deer (Cervus elaphus) singular or irregular EA treatment could only stimulate castrated male, normal or ovariectomised females to grow pedicles, but not antlers. The present study was set out to test whether these EA-induced pedicles in red deer failed to give rise to antlers was because they were constitutively incapable of doing so, or because the plasma T profile naturally exhibited in intact stags was not achieved by the androgen treatment used in these previous studies. Eight castrated red deer stag calves, 3 freemartins (females which were born co-twin to males), and 3 normal female red deer were used in the present study and treated with EA, either as biweekly injections for the castrates or as implants for freemartin and females until the late stage of pedicle growth. Blood sampling was carried out biweekly for the analyses of plasma T and IGF1 concentration. The results showed that the natural plasma T profile in the experimental deer was successfully mimicked through regular EA treatment and subsequent withdrawal at late pedicle growth stage. All castrated males, 2 out of 3 freemartin, and 1 out of 3 normal female red deer formed not only pedicles, but also antlers. Based on these results, we conclude that EA-induced pedicles at least in red deer of the genus Cervus, like those in the genus Odocoileus, are constitutively capable of giving rise to antlers, if they are of sufficient height.
We examined fetal sheep adrenal glands from 99 to 130 days of gestational age (dGA) to see how connexin 43 (Cx43), the major if not the only adult adrenal gap junction protein, changes expression as the adrenal cortex emerges from the well-documented refractory period to participate in labor and delivery. Immunocytochemical technique and Western blot were used to examine changes in the quantity and quality of Cx43. In addition, adrenal glands of ACTH infused fetuses or of fetuses from dexamethasone injected ewes underwent image analysis quantification after Cx43 immunostaining. Finally, fetal adrenal glands, from fetuses splanchnic nerve sectioned (SPLX) at 125 dGA, were examined for the pattern of Cx43 immunostaining at 131 days of gestation. From 100 to 130 dGA, the amount of Cx43 in cells of the adrenal cortex increased steadily while the pattern of immunoreactivity changed from predominantly cytoplasmic to membrane bound. At 100-103 dGA, ACTH infusion increased the size of the cortex, but decreased the expression of Cx43 per unit area while dexamethasone had no effect on either parameter. Lastly, the expression of Cx43 as a membrane bound protein was not delayed or reversed by SPLX. We conclude that the described changes in Cx43 are most intriguing given their temporal relationship to the described preparturient increases in ACTH and cortisol in peripheral fetal plasma as term approaches and deserve further investigation.