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Biomedical subjects

Q Lu

Publications and source records attributed to Q Lu.

At least 91 records · Page 5Linked to original sources

Role of the heart in the loss of aeration characterizing lower lobes in acute respiratory distress syndrome. CT Scan ARDS Study Group.

In the acute respiratory distress syndrome (ARDS), lower lobes appear essentially non-aerated in contrast to upper lobes whose aeration can be preserved in some patients. The aim of this study was to assess the mechanical compression exerted by the heart on lower lobes in patients with ARDS. Fourteen healthy volunteers and 38 patients with ARDS free of left ventricular failure were studied. Cardiorespiratory parameters were recorded and the cardiac dimensions, the pressure exerted by the heart on subjacent lower lobes, and the gas tissue ratio of lower lobes in the supine position were measured using computer tomography and Lungview, a specifically designed software. In patients with ARDS, the heart was larger and heavier than in healthy volunteers. The enlargement of the heart was mainly related to a left cardiac protrusion and the pressure exerted by the left heart on the lower lobes was higher in patients with ARDS than in healthy volunteers (8 +/- 3 g. cm(-)(2) versus 6 +/- 1 g. cm(-)(2), p < 0.01). As a consequence, the faction of gas represented 62% of the left lower lobes in healthy volunteers and 12% only in patients with ARDS. The present study demonstrates that apart from the already known anteroposterior and cephalocaudal gradients of pressure depending on the lung weight and abdominal pressure, the heart plays an important role in the dramatic loss of aeration characterizing lower lobes of patients with ARDS lying in the supine position.

Adult↗

A computed tomographic scan assessment of endotracheal suctioning-induced bronchoconstriction in ventilated sheep.

This study was directed at assessing changes in bronchial cross-sectional surface areas (BCSA) and in respiratory resistance induced by endotracheal suctioning in nine anesthetized sheep. Cardiorespiratory parameters (Swan-Ganz catheter), respiratory resistance (inspiratory occlusion technique), BCSA, and lung aeration (computed tomography) were studied at baseline, during endotracheal suctioning, and after 20 consecutive hyperinflations. Measurements performed initially at an inspired oxygen fraction (FI(O(2))) of 0.3 were repeated at an FI(O(2)) of 1.0. At an FI(O(2)) of 0.3, endotracheal suctioning resulted in atelectasis, a reduction in BCSA of 29 +/- 23% (mean +/- SD), a decrease in arterial oxygen saturation from 95 +/- 3% to 87 +/- 12% (p = 0.02), an increase in venous admixture from 19 +/- 10% to 31 +/- 19% (p = 0. 006), and an increase in lung tissue resistance (DR(rs)) (p = 0. 0003). At an FI(O(2)) of 1.0, despite an extension of atelectasis and an increase in pulmonary shunt from 19 +/- 5% to 36 +/- 2% (p < 0.0001), arterial O(2) desaturation was prevented and BCSA decreased by only 7 +/- 32%. A recruitment maneuver after endotracheal suctioning entirely reversed the suctioning-induced increase in DR(rs) and atelectasis. In three lidocaine-pretreated sheep, the endotracheal suctioning-induced reduction of BCSA was entirely prevented. These data suggest that the endotracheal suctioning-induced decrease in BCSA is related to atelectasis and bronchoconstriction. Both effects can be reversed by hyperoxygenation maneuver before suctioning in combination with recruitment maneuver after suctioning.

Airway Resistance↗

Measurement of pressure-volume curves in patients on mechanical ventilation. Methods and significance.

In critically ill patients measurements of pressure volume curves has been suggested as a method for assessing the severity of lung injury and for monitoring the evolution of the lung disease; it can also guide the ventilatory adjustments to optimize the mechanical ventilation. The static pressure-volume curves are impaired in acute respiratory distress syndrome (ARDS). The evaluation of the lower and upper inflection point on the pressure-volumes curves at the bedside of patients with acute respiratory failure means to apply a "protective ventilatory strategy". The combined application of positive end expiratory pressure (PEEP) to the level of alveolar recruitment and low tidal volume (< 6 ml/kg) ameliorates the lung function and decrease mortality in ARDS patients. Routine monitoring with continuous technique is easy and develops good therapeutic practice.

Air Pressure↗

Acute lung injury after hemorrhagic shock is dependent on gut injury and sex.

Recent studies have established gut-derived lymph rather than portal blood as the major source of toxic mediators after hemorrhagic shock that causes distant organ injury. Similarly, emerging data have identified sex as a major modifier of the response to injury and illness. Thus we tested the hypothesis that female rats would be more resistant to shock-induced lung injury than male rats because females are more resistant to shock-induced gut injury and produce mesenteric lymph that is less toxic to endothelial cells. Male and female rats were subjected to sham or hemorrhagic shock and lung permeability was quantitated by Evans blue dye and protein extravasation into the alveolar space. Next, mesenteric lymph collected from shocked and sham-shocked rats of both sexes was incubated with human umbilical vein endothelial cells (HUVECs) and assayed for toxicity. Trypan blue dye exclusion and the release of lactate dehydrogenase assessed HUVEC viability and injury respectively. Lastly, sections of the terminal ileum were histologically examined for evidence of shock-induced mucosal injury. Male rats but not female rats subjected to hemorrhagic shock had evidence of increased lung permeability and produced mesenteric lymph that was cytotoxic to HUVECs. Shock caused gut injury in the male rats whereas histological evidence of gut injury was not observed in the female rats. Hemorrhagic shock-induced lung injury depends on gut injury and mesenteric lymph appears to be the route by which gut-derived toxic factors exit the gut to cause lung injury. The resistance of female rats to shock-induced lung injury appears to be secondary to their resistance to shock-induced gut injury.

Animals↗

[Polarized populations of T helper cells in patients with chronic hepatitis B virus infection].

OBJECTIVES: To investigate the composition of Th1/Th2/Th3 cells in chronic HBV-infected individuals by determining the expression of IL-4/IFN-gamma/TGF-beta in single CD4+ T cell isolated from the peripheral blood mononuclear cells (PBMCs), and analyze the role of Th cells polarized population in chronic HBV-infection. METHODS: PBMCs from chronic HBV infected individuals were separated routinely, stimulated by PMA/Ionomycin/Monensin, and the production of IL-4/IFN-gamma/TGF-beta by CD4+ T cells in PBMCs was determined by FACS analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta producing T cells ranged from 2.3%-18.6%, 1.1%-8.7% and 0.7%-7.1%, respectively, in CD4+ cells from non-infected individuals. The majority of CD4+ T cells from PBMCs in chronic HBV-infected individuals were Th0 cells. The proportion of Th1 cells increased significantly with the hepatic inflammation activity, and the proportion in active period of chronic hepatitis B was higher than that in nonactive period (P < 0.05). The percentage of Th2 cells in CD4+ T cells from HBV-infected individuals did not differ significantly (P > 0.05), but it was higher than controls (P < 0.05). The percentage of Th3 cells in CD4+ T cells from AsC group was higher than that in CHB group and control (P < 0.05). CONCLUSIONS: Th1 phenotype cytokine are correlated with hepatic inflammation activity of chronic hepatitis B. Th2 cells may be associated with the persistence of HBV infection. Th3 cells cooperating with Th2 cells exert negative immunoregulating action and may be associated with the immune tolerance state of chronic HBV infection.

Adolescent↗

[Single cell analysis of H(2)O(2) mediated Fas mRNA expression and Ca(2+) influx in LO(2) cells].

OBJECTIVE: To investigate whether apoptotic injury is induced by Fas mRNA expression mediated by H(2)O(2) and concerned with intracellular Ca(2+) unbalance at a single cell level. METHODS: Fas mRNA expression in human hepatocyte (LO(2) cell) was analyzed by whole-cell patch-clamp combined with single cell reverse transcription polymerase chain reaction (RT-PCR). Cytosolic Ca(2+) concentration was measured with another whole-cell patch-clamp combined with single-cell microfluorescence [Ca(2+)] i measurement at the same time. The index of early phase apoptotic cells (Annexin-V(+) cells) measured with flow cytometry (FCM) and the hepatocytic morphological changes were observed by scanning electron microscopy. RESULTS: Fas mRNA of LO(2) cells cultured with H(2)O(2) (10 micromol/L) was expressed at 2 h. The single cell [Ca(2+)] i analyzed by another whole-cell patchclamp increased to 1 115 nmol/L +/- 227 nmol/L (P < 0.01, t = 13.37); at the same time, an elevated Ca(2+) wave was recorded. The index of Annexin-V(+) cells was as high as 16.18 +/- 0.65 (P < 0.01, t = 48.41), and the membrane surface protuberances were observed. CONCLUSIONS: The activation of Fas mRNA, as a major apoptotic factor mediated by H(2)O(2) in LO(2) cells, is probably associated with the imbalance of intracellular Ca(2+).

Apoptosis↗

[Predictor of effect of interferon-alpha on patients with hepatitis B: Th1/Th2 type cytokines].

OBJECTIVE: To investigate the relationship between the expression of Th1/Th2 type cytokines and the effect of interferon-alpha therapy. METHODS: Th1/Th2 type cytokines were detected by ELISA and RT-PCR in 23 patients with chronic hepatitis B who were treated with interferon-alpha for 24 weeks. RESULTS: The levels of IFN-gamma in the supernatant of PBMC cultures of the patients with hepatitis B were slightly lower than those of the controls. However, the levels of IL-4 were higher in the patients than in the controls. Cytokines measurements during IFN-alpha treatment showed a trend toward decreased levels of IL-4 at 4, 12 and 24 weeks. However, the levels of IFN-gamma were slightly increased following IFN-alpha treatment. In patients with complete response to IFN-alpha, the levels of IFN-gamma were higher than that of pre-treatment at 24 weeks following IFN-alpha treatment, and the levels of IL-4 decreased obviously at 12 and 24 weeks. The mRNA levels of Th1/Th2 type cytokines were positively correlated with the levels of supernatant. CONCLUSION: (1) The expression of Th2 type cytokines is predominant in patients with chronic hepatitis B. (2) The effect of interferon-alpha therapy may play a role in modulating the balance of Th1/Th2 type cytokines. (3) Variations of the levels of Th1/Th2 type cytokines could be used as a predictor of clinical response during interferon-alpha treatment.

Adolescent↗

[A cohort study on the relationship between vegetable intake and risks of lung cancer in the Tin Corporation (YTC) miners in Yunnan].

OBJECTIVE: To understand the relationship between vegetable intake and risk of lung cancer in the Tin Corporation (YTC) miners in Yunnan. METHODS: The reproducibility and validity of frequency of vegetable intake in Food Frequency Questionnaire (FFQ) were studied and the correlations between different vegetable intake and frequency and lung cancer relative risk among high risk population of lung cancer by Chi-square, single- and multi-Cox regression were analyzed. RESULTS: Results showed that the reproducibility and validity of wax gourd, cucumber, spinach, wild celery, fresh bush pepper, fresh soybean, sweet potatoes, asparagus, fresh bamboo shoot were good (r = 0.20 - 0.33, P < 0.05); There were significantly different incidences of lung cancer in different frequencies of wax gourd, cucumber, wild celery, fresh bush pepper out of 11 vegetables intake, and also in different total vegetable intakes (chi(2) = 8.83 - 30.64, P < 0.05). 11 vegetables and total vegetable intake were significantly negatively correlated with risks of lung cancer (RR < 1, P < 0.05). Only 2 vegetable frequencies were negatively correlated with risk of lung cancer by adjusting confounders such as age, occupational history, and smoking (P < 0.05). CONCLUSION: This suggested that vegetables intake may have a role in decreasing the incidence of lung cancer.

Adult↗

[Comparison of the effects of xianyu tablet and its component on electrophoretic mobility of serum LDL and expression of ET-1 mRNA and iNOS mRNA of vessel wall in atherosclerotic rabbits].

Xiaoyu tablet, a compound preparation of Chinese herbal medicines, consists of Radix Salviae Miltiorrhizae(SM) and Fructus Crataegi(FC) extracts. To determine whether the proved recipe was reasonable, the effects of Xiaoyu tablet and its component on electrophoretic mobility of serum LDL and expression of ET-1 mRNA and iNOS mRNA of vessel wall in atherosclerotic rabbits were observed. The results indicated that inhibition of expression iNOS mRNA in vessel wall by Xiaoyu tablet was the same as its single extract of SM or FC, but Xiaoyu talbet was superior to SM or FC extract in reduction of electrophoretic mobility of serum LDL and inhibition of ET-1 mRNA expression in vessel wall. These results suggested that there was obvious synergism on prevention and treatment of atherosclerosis when both of the Chinese herbal medicines were simultaneously used.

Animals↗

Effects of novel 17-azolyl compounds on androgen synthesis in vitro and in vivo.

17-Azolyl steroids were synthesized and evaluated as inhibitors of androgen synthesis in vitro and in vivo. Several of the novel compounds exhibit potent noncompetitive inhibition of human 17alpha-hydroxylase/C17,20-lyase with IC50 values ranging from 7 to 90 nM, and Ki values from 1.2 to 41 nM. VN/85-1 and VN/108-1 were the most potent inhibitors against this enzyme with IC50 value of 8 nM (Ki of 1.2 nM) and 7 nM (Ki of 1.9 nM), respectively. VN/107-1, VN/108-1 and VN/109-1 also showed moderate inhibition of 5alpha-reductase in human prostatic microsomes. Normal adult male rats were treated with these novel 17-azolyl steroidal compounds at a dose level of 50 mg/kg, s.c., for 14 consecutive days, sacrificed 1-2 h after the last administered dose and blood, prostate and other tissues were collected. The organs were weighed and tissue concentrations of testosterone (T) and dihydrotestosterone (DHT) were measured. Tissue T levels were significantly (p<0.05) lower in rats treated with the novel 17-azolyl steroids by more than 50% compared to the control group. Similarly, the concentration of DHT in the serum and prostates was significantly (p<0.05) diminished in rats treated with the 17-azolyl steroids by 39-80% compared to the control group. Furthermore, the wet weights of the prostates and seminal vesicles were significantly (p<0.05) reduced by several of the novel steroids. Although only one dose was evaluated in these studies, VN/85-1 was the most effective compound and reduced prostatic androgen levels by more than 80% and the wet weights of the prostate and seminal vesicles in rats by about 50%. These findings suggest that these novel compounds may provide useful leads for the research and development of suitable agents for the treatment of androgen dependent prostate cancer.

Androgens↗

[Hepatitis B virus core promoter mutations in patients with fulminant hepatitis].

OBJECTIVE: To detect hepatitis B virus core promoter (CP) mutations in patients with fulminant hepatitis. METHODS: Polymerase chain reaction amplified serum HBV DNA fragments were directly sequenced. RESULTS: There were 2-12 nucleotide substitutions in CP region in the 7 subacute fulminant hepatitis patients studied. An 11 bp nucleotides insertion was found in one patient. Mutations in CP were usually seen in the first and the second A T rich regions. The A to T mutation at nt 1,762 and G to A mutation at nt 1,764 were found in 4 cases, 3 of them were HBeAg negative. The third A T rich region was kept intact in all the 7 patients, so did the initial site of HBV replication (DR1) and the initial site of mRNA transcription (1,783/1784 or 1,790 +/- 1 for precore mRNA and 1818 for pregenome-C/P mRNA). CONCLUSION: CP mutations in patients with fulminant hepatitis are common, most of the CP variations occur in the first and the second A T rich regions, and these mutations may impede the transcription of precore mRNA and affect the expression of HBeAg.

Amino Acid Sequence↗

[An inquire into the infection of a new virus(TTV)].

OBJECTIVE: The aim of this study is to find out the prevalence of TTV in the cryptogenic hepatitis' and the clinical features of TTV infected patients. METHODS: TTV DNA in the serum was tested by nested PCR and the clinical data was analyzed. RESULTS: Infection rate of the TTV in cryptogenic hepatitis was 38.6%. It was a sporadic disease, and involved mainly the adults, with no sexual difference. The symptoms were notable, often with jaundice, but the level of transaminase were elevated moderately. Histology revealed the portal area inflammation. If accompanied with other disease, the illness would be exacerbated. CONCLUSION: TTV would be accounted for part of the reason in patients with cryptogenic hepatitis.

Adult↗

Phosphorylated tau can promote tubulin assembly.

Phosphorylation can affect the function of microtubule-associated protein tau. Here, the human brain tau with 441 amino acids was phosphorylated by cyclic-AMP-dependent protein kinase (PKA) or glycogen synthase kinase-3beta. PKA-phosphorylated tau (2.7 mol phosphates/mol) does not promote tubulin assembly as judged by spectrophotometric and atomic force microscopy measurements, unless trimethylamine N-oxide (TMAO), a natural occurring osmolyte, is included in these assays. TMAO is also found to promote tubulin assembly of glycogen synthase kinase-3beta-phosphorylated tau (1.6 mol phosphates/mol). TMAO does not act by causing a chemical dephosphorylation of phosphorylated tau, but it acts to overcome the functional deficit caused by phosphorylation. PKA-phosphorylated tau binds to tubulin in the presence of TMAO and lowers the critical concentration of tubulin needed for assembly. From these data, we conclude that PKA-phosphorylated tau retains the ability to bind tubulin and promote tubulin assembly. TMAO is required, however, to sensitize the reaction. Possible uses of TMAO in relation to studies of tubulin assembly in vitro, in intact cells, and in relation to Alzheimer's disease are presented in this report.

Brain Chemistry↗

Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway.

In response to DNA damage and replication blocks, cells activate pathways that arrest the cell cycle and induce the transcription of genes that facilitate repair. In mammals, ATM (ataxia telangiectasia mutated) kinase together with other checkpoint kinases are important components in this response. We have cloned the rat and human homologs of Saccharomyces cerevisiae Rad 53 and Schizosaccharomyces pombe Cds1, called checkpoint kinase 2 (chk2). Complementation studies suggest that Chk2 can partially replace the function of the defective checkpoint kinase in the Cds1 deficient yeast strain. Chk2 was phosphorylated and activated in response to DNA damage in an ATM dependent manner. Its activation in response to replication blocks by hydroxyurea (HU) treatment, however, was independent of ATM. Using mass spectrometry, we found that, similar to Chk1, Chk2 can phosphorylate serine 216 in Cdc25C, a site known to be involved in negative regulation of Cdc25C. These results suggest that Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Activation of Chk2 might not only delay mitotic entry, but also increase the capacity of cultured cells to survive after treatment with gamma-radiation or with the topoisomerase-I inhibitor topotecan.

Alkylating Agents↗

Effects of 6 months of moderate aerobic exercise training on immune function in the elderly.

The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer (NK) cell number and function. Previously sedentary elderly (age = 65 +/- 0.8 years) subjects were randomly assigned to supervised 3 time/week exercise intervention group (EXC, n = 14) or flexibility/toning control group (FT-CON, n = 15). Fasting resting blood samples were drawn prior to and after the 6 month intervention. The EXC group exhibited a significant (P < 0.05) 20% increase in VO2 max, whereas the FT-CON group had a smaller non-significant (P = 0.07) increase (9%). Immune results revealed that, in general, changes in immune function in response to 6 months of exercise training at an average intensity of 52% heart rate reserve (HRR) were similar when compared to FT-CON who exercised at approximately 21% HRR. There were no intervention-induced changes in total white blood cell, neutrophil, lymphocyte, monocyte, eosinophil, or basophil blood counts. Furthermore, the percentage and number of CD3+, CD4+ and CD8+ T cells in the blood remained unchanged. There was a tendency for the percentage and number of CD4+ and CD8+ näive cells (CD45RA+) to increase and for CD4+ memory cells (CD45RO+) to decrease post-intervention, especially in FT-CON. Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation: the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase (P < 0.1) in the EXC group with little change in FT-CON. We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function, while not affecting others, in previously sedentary elderly.

Aged↗

IKK1-deficient mice exhibit abnormal development of skin and skeleton.

IkappaB kinases (IKKs) IKK1 and IKK2 are two putative IkappaBalpha kinases involved in NF-kappaB activation. To examine the in vivo functions of IKK1, we generated IKK1-deficient mice. The mutant mice are perinatally lethal and exhibit a wide range of developmental defects. Newborn mutant mice have shiny, taut, and sticky skin without whiskers. Histological analysis shows thicker epidermis, which is unable to differentiate. Limbs and tail are wrapped inside the skin and do not extend properly out of the body trunk. Skeleton staining reveals a cleft secondary palate, split sternebra 6, and deformed incisors. NF-kappaB activation mediated by TNFalpha and IL-1 is diminished in IKK1-deficient mouse embryonic fibroblast (MEF) cells. The IKK complex in the absence of IKK1 is capable of phosphorylating IkappaBalpha and IkappaBbeta in vitro. Our results support a role for IKK1 in NF-kappaB activation and uncover its involvement in skin and skeleton development. We conclude further that the two related kinases IKK1 and IKK2 have distinct functions and can not be substituted for each other's functions.

Animals↗

Regulation of tau phosphorylation in microtubule fractions by apolipoprotein E.

In Alzheimer's disease (AD), a family of proteins collectively named tau are displaced from their normal association with microtubules and are found in in a hyperphosphorylated state deposited into paired helical filaments (PHFs). PHFs are the hallmark cytoskeletal pathology of the disease, and the degree of PHF pathology correlates with the clinical severity of AD. Certain apolipoprotein E (apoE) isoforms have been identified as either risk or protective factors for AD, and one of the proposed mechanisms involves an interaction and potentially modulatory effects on tau hyperphosphorylation by the different apoE isoforms. In these studies, we directly tested the effects of apoE, E2, E3, and E4 on AD-like phosphorylation of tau in brain microtubule fractions. We found that apoE attenuates tau hyperphosphorylation in the fractions, but the pattern was indistinguishable for the different isoforms.

Adenosine Triphosphate↗

Tyro-3 family receptors are essential regulators of mammalian spermatogenesis.

We have generated and analysed null mutations in the mouse genes encoding three structurally related receptors with tyrosine kinase activity: Tyro 3, Axl, and Mer. Mice lacking any single receptor, or any combination of two receptors, are viable and fertile, but male animals that lack all three receptors produce no mature sperm, owing to the progressive death of differentiating germ cells. This degenerative phenotype appears to result from a failure of the tropic support that is normally provided by Sertoli cells of the seminiferous tubules, whose function depends on testosterone and additional factors produced by Leydig cells. Tyro 3, Axl and Mer are all normally expressed by Sertoli cells during postnatal development, whereas their ligands, Gas6 and protein S, are produced by Leydig cells before sexual maturity, and by both Leydig and Sertoli cells thereafter. Here we show that the concerted activation of Tyro 3, Axl and Mer in Sertoli cells is critical to the role that these cells play as nurturers of developing germ cells. Additional observations indicate that these receptors may also be essential for the tropic maintenance of diverse cell types in the mature nervous, immune and reproductive systems.

Animals↗