Prolactin-like protein-A gene structure and chromosomal mapping.
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Amino Acid Sequence↗
Biomedical subjects
G Dai
Publications and source records attributed to G Dai.
Effects of modulating TGF-beta 1 on immune responses to mycobacterial infection in guinea pigs.
SETTING: TGF-beta 1 has been implicated as an important mediator of immuno-suppression in clinical tuberculosis. OBJECTIVE: The objective was to determine the role of TGF-beta 1 in experimental pulmonary tuberculosis in the guinea pig. DESIGN: Groups of guinea pigs, maintained on either a low protein (LP) diet or an isocaloric high protein (HP) diet, were challenged via the respiratory route with virulent Mycobacterium tuberculosis H37Rv. Ten days post-infection, guinea pigs were given daily intraperitoneal injections of recombinant human TGF-beta 1 (rhTGF-beta 1 tau for 10 consecutive days). Following the treatment, guinea pigs were euthanized, and PPD-induced proliferation of peripheral blood mononuclear cells (PBMCs) was assessed and disease resistance measured by recovery of mycobacteria from the lungs and spleens. In a second set of experiments, groups of HP and LP guinea pigs were vaccinated with attenuated M. tuberculosis H37Ra. Six weeks later, the effects of rhTGF-beta 1 on lymphoproliferation and cytokine production were determined. RESULTS: Protein deficiency significantly impaired host anti-tuberculosis resistance, as expected. Treatment with rhTGF-beta 1 significantly increased mycobacterial loads in the tissues of guinea pigs and decreased the PPD-induced proliferation of PBMCs from both LP and HP guinea pigs. PPD-driven lymphoproliferation, TNF-alpha and IFN production were significantly suppressed in vaccinated, protein-deficient guinea pigs, and rhTGF-beta 1 further inhibited lymphoproliferation and cytokine production. CONCLUSION: Both in vivo and in vitro results indicate that TGF-beta 1 exerts immunosuppressive activity and exacerbates the progression of experimental pulmonary tuberculosis in both normally nourished and protein-deficient guinea pigs.
Animals↗
Mechanisms of vaccine-induced resistance in a guinea pig model of pulmonary tuberculosis.
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Animals↗
The effects of external compression on venous blood flow and tissue deformation in the lower leg.
External pneumatic compression of the lower legs is effective as prophylaxis against deep vein thrombosis. In a typical application, inflatable cuffs are wrapped around the patient's legs and periodically inflated to prevent stasis, accelerate venous blood flow, and enhance fibrinolysis. The purpose of this study was to examine the stress distribution within the tissues, and the corresponding venous blood flow and intravascular shear stress with different external compression modalities. A two-dimensional finite element analysis (FEA) was used to determine venous collapse as a function of internal (venous) pressure and the magnitude and spatial distribution of external (surface) pressure. Using the one-dimensional equations governing flow in a collapsible tube and the relations for venous collapse from the FEA, blood flow resulting from external compression was simulated. Tests were conducted to compare circumferentially symmetric (C) and asymmetric (A) compression and to examine distributions of pressure along the limb. Results show that A compression produces greater vessel collapse and generates larger blood flow velocities and shear stresses than C compression. The differences between axially uniform and graded-sequential compression are less marked than previously found, with uniform compression providing slightly greater peak flow velocities and shear stresses. The major advantage of graded-sequential compression is found at midcalf. Strains at the lumenal border are approximately 20 percent at an external pressure of 50 mmHg (6650 Pa) with all compression modalities.
Blood Flow Velocity↗
Distinct regulatory regions from the prolactin-like protein C variant promoter direct trophoblast giant cell versus spongiotrophoblast cell-specific expression.
PRL-like protein C variant (PLP-Cv) is a newly identified member of the PRL family. PLP-Cv is specifically expressed in the chorioallantoic placenta by two distinct cell populations: trophoblast giant cells and spongiotrophoblast cells. To gain some insight regarding the control of PLP-Cv gene expression and the regulatory factors controlling trophoblast giant cell and spongiotrophoblast cell lineages, we have initiated a structural and functional analysis of the PLP-Cv promoter. The activities of a series of PLP-Cv promoter constructs, ranging in size from 4.5 kb to 50 bp, ligated to a luciferase reporter have been assessed in the Rcho-1 trophoblast cell line (restricted to trophoblast giant cell differentiation) and in a primary spongiotrophoblast cell culture system after transient transfection. PLP-Cv promoter constructs containing 4.5 kb to 149 bp of 5'-flanking DNA possessed full activity in the trophoblast giant cell model. A region located between -149 and -124 bp upstream of the PLP-Cv transcription start site was found to be essential for activation of the PLP-Cv promoter. Spongiotrophoblast cells required additional PLP-Cv 5'-flanking DNA for full activity. A region located between -2518 and -2242 bp upstream of the PLP-Cv transcription start site significantly enhanced PLP-Cv promoter in spongiotrophoblast cells. In conclusion, mechanisms underlying the activation of the PLP-Cv promoter are different in trophoblast giant cells vs. spongiotrophoblast cells.
Animals↗
Uterine natural killer cells are targets for a trophoblast cell-specific cytokine, prolactin-like protein A.
PRL-like protein A (PLP-A) is a member of the PRL family expressed in trophoblast cells coincident with establishment of the chorioallantoic placenta. The purpose of this investigation was to identify targets for PLP-A. Using an alkaline phosphatase-tagging strategy, we show that PLP-A specifically interacts with a population of natural killer (NK) lymphocytes within the mesometrial compartment of decidua from pregnant and pseudopregnant rats. These observations are supported by the codistribution of PLP-A targets with cells expressing the rat NK cell surface marker, gp42, the absence of PLP-A binding in conceptuses from NK cell-deficient tg epsilon26 mice, and the specific interaction of PLP-A with a rat NK cell line, RNK-16. We have further demonstrated that PLP-A effectively suppresses RNK-16 cell cytolytic activities. Our results provide evidence for a new paradigm of embryonic-maternal communication involving a PLP-A signaling pathway between trophoblast cells and uterine NK lymphocytes.
Alkaline Phosphatase↗
Quantitative MR imaging of carpal tunnel syndrome.
OBJECTIVE: Previous MR imaging studies have produced evidence of changes to structures within the wrist believed to be associated with carpal tunnel syndrome. In an attempt to resolve the conflicting and inconclusive results of these studies, we report here the results of an MR imaging study at a field strength of 3.0 T, which is higher than that previously reported. SUBJECTS AND METHODS: Patients with carpal tunnel syndrome and control groups of asymptomatic subjects were studied using MR imaging. We evaluated electrophysiologically the median nerve function of the affected wrists of all patients. A gradient-recalled echo pulse sequence was used to study 13 3-mm-thick slices within the wrist of each patient or asymptomatic subject. Spatial resolution was approximately 0.3 x 0.3 mm2. The median nerve and other structures associated with the carpal tunnel, which were clearly shown on the MR images, were analyzed to yield structural data. RESULTS: Analysis revealed that the cross-sectional area of the nerve within and proximal to the carpal tunnel was approximately 50% larger in patients with carpal tunnel syndrome than in asymptomatic subjects. We found no significant difference in the area of the nerve within the carpal tunnel compartment compared with the area of the nerve proximal to the carpal tunnel either in patients or in asymptomatic subjects. Also, flattening of the nerve on entering the carpal tunnel was not significantly different in patients than in asymptomatic subjects. In patients an increase in the palmar bowing of the flexor retinaculum was found only at the level of the hamate compared with that found in asymptomatic subjects. The cross-sectional area of the carpal tunnel was of a similar size in patients and in asymptomatic subjects. Comparison of electrodiagnostic results indicated no correlations between the MR parameters and electrophysiologic dysfunction of the median nerve for patients. CONCLUSION: The only statistically significant differences found between patients with carpal tunnel syndrome and asymptomatic subjects were that the median nerve was approximately 50% larger within and proximal to the carpal tunnel in patients with carpal tunnel syndrome and palmar bowing of the flexor retinaculum occurred in patients only at the level of the hamate.
Adult↗
An interleaved T1-T2* imaging sequence for assessing myocardial injury.
We developed a sequence by which T1- and T2*-weighted images can be acquired simultaneously and demonstrated its validity for assessing myocardial injury. The interleaved T1-T2* imaging sequence consisted of one preparatory pulse (a 90 degrees pulse) and a gradient-echo imaging sequence with a dynamically variable echo time varying between 4.2 msec for T1-weighted imaging and 15 msec for T2*-weighted imaging. The sequence was tested and validated on isolated blood-perfused pig hearts (n = 4). We found that contrast agent-induced T1 and T2* effects were clearly delineated during the first-pass and steady-state periods of a contrast agent (gadolinium diethylenetriaminopentaacetic acid). With a bolus injection of contrast agent, the maximum changes in T2* signal intensity occur significantly earlier than the changes in T1 signal. We also found that the maximum change in T1 signal intensity during the first pass of contrast agent was significantly greater in a reperfused-infarcted region than in normal regions. The suppression of T2* signal was similar in both regions. At steady state of contrast agent, T2* signal intensities gradually recovered to a significantly higher level in the reperfused-infarcted region than in normal regions. This suggests that the contrast agent diffused into the intracellular space, indicating the loss of cell membrane integrity. As a result, T1 signal intensity was also higher in the reperfused-infarcted myocardium than in normal myocardium. T1- and T2*-weighted images can be acquired simultaneously. The interleaved T1-T2* sequence is useful in assessing myocardial injury.
Animals↗
[Carcinoma of the lips developing in discoid lupus erythematosus].
OBJECTIVE: This clinical study was designed to learn the diagnosis and treatment of lip carcinoma developing in discoid lupus erythematosus. METHODS: One hundred and eighty-one of squamous cell carcinoma of the lips treated in our department from 1980 to 1995 were retrospectively studied. RESULTS: Ten cases of the 181 lip carcinoma (5.5%) had concomitant discoid lupus erythematosus (DLE) of the vermilion border of the lower lip. CONCLUSION: Bleomycin or radiotherapy is the best treatment for the disease.
Adult↗
[Follow-up study of human herpesvirus 6 and human cytomegalovirus infection in organ transplantation recipients].
OBJECTIVE: To trace the study of the prevalence and adverse factors of human herpesvirus 6(HHV-6) and human cytomegalovirus(HCMV) infection in organ transplantation recipients. METHOD: Blood and urine specimens were detected by virus isolation, polymerase chain reaction(PCR), and indirect immunofluorescent assay. RESULT: HCMV and HHV-6 isolation rate were 25.8% and 32.3%, respectively. Anti-HCMV IgM and anti-HHV-6 IgM positive rates before operation were 0% and 3.2%, their positive rates after operation were 19.4% and 25.8%, respectively. HCMV-DNA and HHV-6-DNA positive rates before operation were 35.5% and 45.2%; their positive rates after operation were 45.2% and 61.3%, and kept the high positive rates for a long period. The patients who died within 3 months were all complicated by HCMV and/or HHV-6 productive infection. The productive infection rates of HCMV and HHV-6 were 25.8% and 32.2%, respectively. CONCLUSION: The majority of HCMV and HHV-6 infection are reactivation. Productive infection attack at 2 weeks after operation, reaches the peak at 3-4 weeks after operation, and attacks at anytime within 3 months. HCMV and/or HHV-6 productive infection are fatal to recipients.
Cytomegalovirus Infections↗
N-linked glycosylation of the thyroid Na+/I- symporter (NIS). Implications for its secondary structure model.
The Na+/I- symporter (NIS), a 618-amino acid membrane glycoprotein that catalyzes the active accumulation of I- into thyroid cells, was identified and characterized at the molecular level in our laboratory (Dai, G., Levy, O., and Carrasco, N. (1996) Nature 379, 458-460). Because mature NIS is highly glycosylated, it migrates in SDS-polyacrylamide gel electrophoresis as a broad polypeptide of higher molecular mass (approximately 90-110 kDa) than nonglycosylated NIS (approximately 50 kDa). Using site-directed mutagenesis, we substituted both separately and simultaneously the asparagine residues in all three putative N-linked glycosylation consensus sequences of NIS with glutamine and assessed the effects of the mutations on function and stability of NIS in COS cells. All mutants were active and displayed 50-90% of wild-type NIS activity, including the completely nonglycosylated triple mutant. This demonstrates that to a considerable extent, function and stability of NIS are preserved in the partial or even total absence of N-linked glycosylation. We also found that Asn225 is glycosylated, thus proving that the hydrophilic loop that contains this amino acid residue faces the extracellular milieu rather than the cytosol as previously suggested. We demonstrated that the NH2 terminus faces extracellularly as well. A new secondary structure model consistent with these findings is proposed.
Amino Acid Sequence↗
Nutritional modulation of host responses to mycobacteria.
Nutritional status determines the generation and functioning of cellular and molecular components of the immune system which are responsible for host resistance to various infectious diseases, including tuberculosis. Studies carried out by us and others have demonstrated that malnutrition exerts detrimental effects on many aspects of host immune responses against mycobacterial infection. First, dietary deficiencies of single nutrients, such as protein and zinc, cause thymic atrophy and impair the generation and maturation of T lymphocytes in animal models of tuberculosis, resulting in reduced number of immunocompetent T cells in lymphoid compartments including the blood. Second, deficiencies of protein, zinc and vitamin D impair T-cell functions, including decreased production of the Th1 cytokines IL-2 and IFN-gamma, and depressed dermal tuberculin reactions and PPD-induced lymphoproliferation in guinea pigs and mice infected with virulent Mycobacterium tuberculosis. Third, protein malnutrition causes trapping or sequestration of reactive T lymphocytes and loss of tuberculosis resistance following BCG vaccination. Finally, protein malnutrition potentiates M. tuberculosis H37Rv-infected monocyte-macrophages to produce higher levels of TGF-beta1 a cytokine which has been implicated as a likely mediator of immunosuppression and immunopathogenesis in tuberculosis.
Animals↗
[Regulation of myocardium beta-adrenoceptors pathway in ventricular remodeling of heart failure patients].
To study the role of myocardium beta-adrenoceptors pathway in ventricular remodeling of heart failure patients. beta-adrenegic receptor density (Bmax) and the content of cAMP were measured in the papillae of left ventricle and blood lymphocyte of 20 patients suffered from heart failure (CHF) (NYHZ classification II to III) Bmax were investigated using 3H-dihydroalpheolol as ligand. cAMP were assessed by competitive immunoassay. Left ventricle mass index (LVMI) were measured using echocardiogram. The results showed that the Bmax and cAMP in failing myocardium significantly negatively correlated with LVMI (r = -0.77, P < 0.01 and r = -0.46 P < 0.05 respectively); the Bmax of myocardium and blood lymphocyte in CHF patients with NYHA III (63 +/- 12 fmol/mgpro and 514 +/- 115 fmol/10(7) cell) significantly lowered than that of NYHA II patients (94 +/- 20 fmol/mgpro and 702 +/- 138 fmol/10(7) cell); and the Bmax of myocardium and blood lymphocyte in patients with abnormal LVMI (62 +/- 12 fmol/mgpro and 516 +/- 122 fmol/10(7) cell) decreased more significantly than that with normal LVMI patients; even in nromal LVMI patients (92 +/- 21 fmol/mgpro and 682 +/- 146 fmol/10(7) cell), the Bmax of blood lymphocyte was already decreased (P < 0.01), when comparing with controls. The intralymphocyte cAMP content sygnificantly decreased than that of controls (P < 0.05). These results indicated that Bmax could reflect the severity of ventricle remodeling and the impairment of myocardium. The regulation of myocardium intracellular messenger transduction was earlier than the pathologic structural change of LV remodeling.
Adult↗
Effect of low HDL combined with hypertriglyceridemia in coronary artery disease patients on PGI2 biological activity in relation to lipid regulating treatment.
The purpose of this study was to investigate the effect of low high-density-lipoprotein (HDL) combined with hypertriglyceridemia in coronary artery disease (CAD) patients on prostaglandin I2 (PGI2) biological activity in relation to lipid regulating treatment. The inhibitory rate of PGI2 on ADP-induced platelet aggregation was used as the index for PGI2 biological activity. Twenty health individuals served as normal controls. CAD group consisted of 20 patients with low HDL combined with hypertriglyceridemia. The results showed that, before the treatment, the stabilizing effect on PGI2 activity decreased significantly in CAD group when compared with the control group (P < 0.01). One month after the treatment, HDL level in CAD group increased significantly and TG level significantly decreased (P < 0.001). The different effect on PGI2 activity was no longer found between CAD group and control group (P > 0.05), further confirming the protecting effect of HDL on PGI2 biological activity. Low HDL is considered as an important risk factor of CAD, therefore, impaired PGI2 biological activity and increased platelet aggregation might be responsible mechanisms. Furthermore, raising HDL level by lipid regulating treatment could restore the protective effect of HDL on PGI2 and might be helpful in the prevention of the acute coronary syndrome.
Coronary Disease↗
The uteroplacental prolactin family and pregnancy.
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Animals↗
Altered cytokine production and impaired antimycobacterial immunity in protein-malnourished guinea pigs.
Protein malnutrition leads to multiple detrimental alterations of host immune responses to mycobacterial infection. In this study, we demonstrated that splenocytes from low-protein (LP) guinea pigs vaccinated 6 weeks previously with attenuated Mycobacterium tuberculosis H37Ra failed to control the accumulation of virulent M. tuberculosis H37Rv in cocultured autologous peritoneal macrophages, despite the fact that they were able to control the accumulation of virulent tubercle bacilli in cocultured syngeneic peritoneal macrophages from normally nourished guinea pigs as successfully as did those from high-protein (HP) counterparts. Vaccine-induced growth control of virulent M. tuberculosis H37Rv in these cocultures appeared to be mediated by CD4 lymphocytes but not CD8 cells. Tuberculin (purified protein derivative [PPD])-induced lymphoproliferation was markedly impaired in vaccinated LP guinea pigs, and the depletion of CD4 lymphocytes significantly decreased lymphocyte proliferation whereas CD8 cell depletion did not. Protein malnutrition also impaired the abilities of cells from vaccinated LP guinea pigs to produce cytokines, including interferon, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta), in response to PPD, despite the demonstration of higher serum levels of TNF-alpha and TGF-beta after an intravenous injection of PPD into LP guinea pigs. In contrast, peritoneal macrophages from protein-malnourished guinea pigs produced a higher level of TGF-beta 4 days after infection in vitro with M. tuberculosis H37Rv than did those from protein adequate controls. These results suggest that dietary protein malnutrition impairs vaccine-induced resistance to M. tuberculosis, in part, by altering the cytokine profile to favor macrophage deactivation.
Animals↗
Placental lactogen-I (PL-I) target tissues identified with an alkaline phosphatase-PL-I fusion protein.
The rat placenta expresses a family of genes related to prolactin (PRL). Target tissues and physiological roles for many members of the PRL family have yet to be determined. In this investigation we evaluated the use of an alkaline phosphatase (AP) tag for monitoring the behavior of a prototypical member of the PRL family, placental lactogen-I (PL-I). A probe was generated consisting of a fusion protein of human placental AP and rat PL-I (AP-PL-I). The AP-PL-I construct was stably expressed in 293 human fetal kidney cells, as was the unmodified AP vector that served as a control. AP activity was monitored with a colorimetric assay in conditioned medium from transfected cells. Immunoreactivity and PRL-like biological activities of the AP-PL-I fusion protein were demonstrated by immunoblotting and the Nb2 lymphoma cell proliferation assay, respectively. AP-PL-I specifically bound to tissue sections known to express the PRL receptor, including the ovary, liver, and choroid plexus. Binding of AP-PL-I to tissues was specific and could be competed with ovine PRL. The results indicate that AP is an effective tag for monitoring the behavior of PL-I and suggest that this labeling system may also be useful for monitoring the actions of other members of the PRL family.
Alkaline Phosphatase↗
A new member of the mouse prolactin (PRL)-like protein-C subfamily, PRL-like protein-C alpha: structure and expression.
In this study, we establish the presence of a unique member of the PRL-like protein-C (PLP-C) subfamily in the mouse, PLP-C alpha, characterize its complementary DNA and gene, and map its chromosomal location and pattern of expression during pregnancy. Mouse PLP-C alpha encodes for a 239 amino acid protein and possesses from 69-71% identity with rat PLP-C, PLP-Cv, PLP-D, and PLP-H. Another feature characteristic of PLP-C subfamily members that is also present in mouse PLP-C alpha is a 6-exon/5-intron gene structure including an aromatic domain encoded by exon 3. Southern analysis with mouse and rat PLP-C subfamily probes suggested the existence of a single mouse PLP-C alpha gene. Mouse PLP-C alpha maps to chromosome 13 along with other members of the mouse PRL family. Expression of mouse PLP-C alpha increases dramatically as gestation advances and is restricted to spongiotrophoblast and trophoblast giant cells of the junctional zone. In summary, we have established the presence of a new PLP-C subfamily member in the mouse and demonstrated its similarity in structure and expression to rat PLP-C subfamily members. This level of conservation between species expands the biological significance of the PLP-C subfamily and provides additional opportunities for genetically evaluating its function.
Amino Acid Sequence↗