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T Du

Publications and source records attributed to T Du.

At least 19 recordsLinked to original sources
PubMed2006

Association of TNF-alpha promoter polymorphisms with the outcomes of hepatitis B virus infection in Chinese Han population.

Host genetic factors and environment factors including hepatitis B virus (HBV) genotypes are widely studied for the different outcomes of HBV infection. Recent studies suggest that tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the viral clearance and host immune response to HBV, and the capacity for TNF-alpha production in individuals is influenced by a major genetic component. In this study, we aimed to explore whether the single-nucleotide polymorphisms (SNPs) of TNF-alpha promoter are associated with the outcomes of HBV infection in the Chinese Han population. One hundred and forty-three spontaneously recovered HBV subjects and 196 chronic hepatitis B patients were recruited in this case-control study in the Beijing area of China. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) and sequence-specific primer-PCR (SSP-PCR) were used to detect the SNPs of five sites in the TNF-alpha promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in two groups were analysed by EPI and EH programs. The presence of the -238GG genotype was significantly correlated with persistence of HBV infection (OR = 4.08, P = 0.02), and -857TT genotype appeared in relation to the spontaneous clearance of HBV (OR = 0.47, P = 0.03). Frequency of haplotype GGCCT (-238/-308/-857/-863/-1031) in the chronic HB group was significantly lower than that in spontaneously recovered group (P = 0.03), and frequencies of haplotypes GGCAT and GGTAT in the chronic HB group were significantly higher than those in the spontaneously recovered group (P = 0.0001, P = 0.0004). In conclusion, TNF-alpha promoter polymorphisms are independently associated with different outcomes of HBV infection.

Adult↗
PubMed2005

Elevated dark adaptation thresholds in traumatic brain injury.

PRIMARY OBJECTIVE: To expand upon earlier findings of elevated dark adaptation (scotopic) thresholds in photosensitive individuals with traumatic brain injury (TBI). METHODS AND PROCEDURES: To assess scotopic thresholds in individuals with TBI (n = 17) manifesting varying degrees of photosensitivity (mild, moderate or marked), but without retinal dysfunction, to those of non-photosensitive, visually-normal individuals (n = 21) using a hand-held dark adaptometer. MAIN OUTCOMES AND RESULTS: The group mean scotopic threshold for the TBI group was significantly higher than that of the visually-normal group. Over 50% (nine out of 17) of the TBI group exhibited elevated thresholds. There was no correlation between the threshold value and degree of photosensitivity. CONCLUSION: The elevated scotopic thresholds suggest an abnormality in cortical gain control. An anomalous adaptive response may develop due to cortical damage, thereby attenuating subjective light sensation.

Adult↗
PubMed2000

Fluid shear stress stimulates prostaglandin and nitric oxide release in bone marrow-derived preosteoclast-like cells.

Bone is a porous tissue that is continuously perfused by interstitial fluid. Fluid flow, driven by both vascular pressure and mechanical loading, may generate significant shear stresses through the canaliculi as well as along the bone lining at the endosteal surface. Both osteoblasts and osteocytes produce signaling factors such as prostaglandins and nitric in response to fluid shear stress (FSS); however, these humoral agents appear to have more profound affects on osteoclast activity at the endosteal surface. We hypothesized that osteoclasts and preosteoclasts may also be mechanosensitive and that osteoclast-mediated autocrine signaling may be important in bone remodeling. In this study, we investigated the effect of FSS on nitric oxide (NO), prostaglandin E(2) (PGE(2)), and prostacyclin (PGI(2)) release by neonatal rat bone marrow-derived preosteoclast-like cells. These cells were tartrate-resistant acid phosphatase (TRAP) positive, weakly nonspecific esterase (NSE) positive, and capable of fusing into calcitonin-responsive, bone-resorbing, multinucleated cells. Bone marrow-derived preosteoclast-like cells exposed for 6 h to a well-defined FSS of 16 dynes/cm(2) produced NO at a rate of 7.5 nmol/mg protein/h, which was 10-fold that of static controls. This response was completely abolished by 100 microM N(G)-amino-L-arginine (L-NAA). Flow also stimulated PGE(2) production (3.9 microg/mg protein/h) and PGI(2) production (220 pg/mg protein/h). L-NAA attenuated flow-induced PGE(2) production by 30%, suggesting that NO may partially modulate PGE(2) production. This is the first report demonstrating that marrow derived cells are sensitive to FSS and that autocrine signaling in these cells may play an important role in load-induced remodeling and signal transduction in bone.

Animals↗
PubMed2000

Regulatory science: a special update from the United States Food and Drug Administration: Preclinical issues and status of investigation of botanical drug products in the United States.

A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products.

Databases, Factual↗
PubMed1999

IL-3 does not affect the allergic airway responses and leukotriene production after allergen challenge in rats.

T cell cytokines are important in asthma. Interleukin (IL)-3, an important growth factor for mast cells and eosinophils has been shown to be increased in the airways of asthmatic subjects, but its precise functions are uncertain. The aim of this study was to determine whether recombinant human (rh) IL-3 affected airway responses, inflammation and leukotriene production after antigen challenge in Brown Norway (BN) rats. Having established that rhIL-3 (>12.5 microg subcutaneously b.i.d. for 4 days) caused a doubling of mast cell numbers in the airways of BN rats, sensitized rats were pretreated with rhIL-3 (50 microg) or vehicle subcutaneously b.i.d. for 4 days. Ovalbumin (OA) challenge was performed and the early (EAR), and late (LAR) airway response and the associated biliary leukotriene (LT) excretion measured. The pulmonary cellularity was evaluated by means of lung digestion 8 h after challenge. IL-3 increased the number of eosinophils isolated from the lungs after antigen challenge (0.77+/-0.23 versus 0.38+/-0.12 x 10(6) cells, p=0.03). However, there were no effects on the numbers of neutrophils, lymphocytes and macrophages. Neither the EAR nor the LAR after OA challenge were altered by IL-3. Likewise biliary cysteinyl-LT excretion was similar in IL-3-treated animals and controls after challenge. In conclusion, interleukin-3 caused an increase in the numbers of mast cells and eosinophils around the airways without affecting the magnitude of either early or late airway responses or mediator release after antigen challenge. The present results suggest that airway inflammation can occur in rats without increasing the allergic asthmatic response.

Allergens↗
PubMed1998

Survey of incidence of Clostridium difficile infection in Canadian hospitals and diagnostic approaches.

A questionnaire relating to Clostridium difficile disease incidence and diagnostic practices was sent to 380 Canadian hospitals (all with > 50 beds). The national questionnaire response rate was 63%. In-house testing was performed in 17.6, 61.5, and 74.2% of the hospitals with < 300, 300 to 500, and > 500 beds, respectively. The average test positivity rates were 17.2, 15.3, and 13.2% for hospitals with < 300, 300 to 500, and > 500 beds, respectively. The average disease incidences were 23.5, 30.8, and 40.3 cases per 100,000 patient days in the hospitals with < 300, 300 to 500, and > 500 beds, respectively. In the 81 hospitals where in-house testing was performed, cytotoxin testing utilizing tissue culture was most common (44.4%), followed by enzyme-linked immunosorbent assay (38.3%), culture for toxigenic C. difficile (32.1%), and latex agglutination (13.6%). The clinical criteria for C. difficile testing were variable, with 85% of hospitals indicating that a test was done automatically if ordered by a doctor. Our results show that C. difficile-associated diarrhea is a major problem in hospitals with > or = 200 beds. Despite a lower disease incidence in smaller hospitals, there was a higher diagnostic test positivity rate. This may reflect the preference of smaller hospitals for culture and latex agglutination tests.

Bacterial Proteins↗
PubMed1997

Microvascular leakage in the airway wall and lumen during allergen induced early and late responses in rats.

The potential contribution of microvascular leakage to airway narrowing during the early (ER) and late (LR) responses following allergen challenge was determined in Brown Norway (BN) rats actively sensitized with ovalbumin (OA). To study leak into the airway wall, rats (n = 46) were challenged 2 weeks later with aerosolized OA, saline, or serotonin (5-HT) to study either ER (n = 25), LR (n = 15), or 5-HT (n = 6) responses. Pulmonary resistance (RL) was used to measure airway narrowing. Microvascular leak was determined by the Evans blue (EB) technique in the airway tissues, and in another group of BN, by EB in bronchoalveolar lavage (BAL) in the airway lumen (n = 43). EB increased in the airways of 5-HT challenged rats (P < 0.05), but not during ER or LR. EB in BAL increased significantly during the ER (101 +/- 31.35 ng/ml BAL), vs saline challenge (10.82 +/- 1.66; P < 0.05) and during the LR at 3, 4, 5, and 7 h following OA challenge compared with controls (P < 0.05). These results suggest that fluid transits rapidly from the airway microvascular circulation and into the airway lumen following allergen challenge. The measurement of EB in BAL can detect microvascular leak into the airway lumen during the ER and LR. Plasma leak into the airway lumen may contribute to the increase in pulmonary resistance observed during ER and LR in BN rats.

Airway Resistance↗
PubMed1997

Considerations for toxicology studies of respiratory drug products.

The standard approaches for the preclinical development of chronically administered drugs also apply to most respiratory drugs. Modifications from the standard preclinical development plan, however, may be necessary if the drug is administered intranasally or by inhalation. Administration by these routes may result in airway toxicity and the intended patient population is often particularly susceptible. Current and former representatives of the Division of Pulmonary Drug Products (CDER, U.S. FDA) present this article to describe general principles of preclinical development for respiratory drug indications. The article addresses drugs intended for administration by the intranasal or inhalation routes. The article describes the types of studies recommended, considers the initial human dose, and discusses dose-escalation strategies in clinical trials. Other areas of special concern with intranasal or inhalation administration include immunotoxicity, reproductive toxicity, types of dosing apparatus, excipients and extractables, and formulation changes. The approaches described in this article are intended as general information and should be adapted to the scientific considerations and circumstances of a particular drug under development.

Humans↗
PubMed1997

[Somatic mutations of PIG-A gene in Chinese patients with paroxysmal nocturnal hemoglobinuria].

OBJECTIVE: To explore the somatic mutations of PIG-A gene in Chinese patients with paroxysmal nocturnal hemoglobinuria (PNH) and to compare these mutations with those in non-Chinese PNH patients. METHODS: Seven overlapping regions of PIG-A cDNA from granulocytes of 4 PNH patients were amplified by RT-PCR. The mutant segments were identified by HA/SSCP and then cloned and sequenced. RESULTS: In 4 Chinese PNH patients five small PIG-A mutations were found, including four single base substitutions (resulting in 1 consense mutations and 3 missense mutations) and one single base deletion causing a frameshift). These mutations were all different and distributed in different locations of the gene. CONCLUSION: The PIG-A mutations in our patients occurred at random sites and no mutation hot spot was found. Compared with Japanese, British, American and Tai patients, Chinese patients seem to have more single base substitutions and less frameshift. The pattern of mutations in our patients is similar to that in Japanese patients but different from that in other races. These suggest that mutagens might be different in the pathogenesis of PNH in different regions.

Asian People↗
PubMed1997

[The clinical implication of detection of CD59(-) cells in paroxysmal nocturnal hemoglobinuria].

OBJECTIVE: To evaluate the significance of glycophosphatidylinositol deficient cells in the diagnosis of paroxysmal nocturnal hemoglobinuria (PNH). METHODS: RBC, and PMN from peripheral blood and mononuclear cells (MNCs) from bone marrow of 29 PNH patients were treated with FITC labelled anti-CD59 monoclonal antibody. Percentages of labelled and unlabelled cells were discriminated by flow cytometry. RESULTS: Normally CD9(-) cells constituted less than 5% in RBCs, PMNs and marrow MNCs, while in each of the patients more than 10% of RBCs were CD59(-) (ranging from 12.8% to 98.0%). More than 10% of PMNs were CD59(-) as well in each of the patients (ranging from 12.0% to 90.1%). Marrow MNCs from the patients contained even more CD59(-) cells (ranging from 17.9% to 73.5%). Ten patients with atypical manifestations were confirmed to be PNH, whereas 7 suspected cases were excluded by this measurement. CONCLUSION: Determination of CD59(-) cells in RBCs, PMNs and more preferably in marrow MNCs could be considered a direct, specific and reliable method for diagnosis of PNH.

CD59 Antigens↗
PubMed1996

Effect of nedocromil sodium on allergen-induced airway responses and changes in the quantity of airway smooth muscle in rats.

BACKGROUND: Allergen exposures induce growth of airway smooth muscle in the Brown Norway rat. OBJECTIVE: The purpose of the study was to examine the role of mediators associated with the early and late responses in the induction of airway smooth muscle growth. METHODS: Nedocromil sodium was administered to block early and late responses in ovalbumin-sensitized and ovalbumin-challenged rats undergoing single or multiple challenges (5 times at 5-day intervals) with ovalbumin. Airway smooth muscle was quantitated by morphometry on lungs removed 2 days after the final challenge. RESULTS: Nedocromil sodium administered before ovalbumin challenge blocked both the early and late responses. When administered 2 hours after ovalbumin challenge, it also blocked the late response. Rats undergoing challenge with aerosolized ovalbumin five times at 5-day intervals were also treated with nedocromil before (n = 10) or 2 hours after (n = 10) each ovalbumin inhalation, respectively. The quantity of airway smooth muscle standardized for size was greater after ovalbumin challenge (0.069 +/- 0.005) compared with saline controls (0.033 +/- 0.003, p < 0.005). Nedocromil significantly reduced the airway smooth muscle (0.036 +/- 0.003, p < 0.005) when administered before ovalbumin. However, the airway smooth muscle in rats that received nedocromil 2 hours after ovalbumin challenge (0.046 +/- 0.003), although lower than in ovalbumin-challenged rats (p < 0.01), was still significantly higher than in saline-treated rats (p < 0.05). CONCLUSIONS: Allergen-induced early responses, late responses, and airway inflammation are antagonized by nedocromil. The mediators of both the early and late responses contribute to allergen-induced airway smooth muscle growth, a process that can be prevented by administration of nedocromil.

Allergens↗
PubMed1996

Tissue-dependent differences in the asynchronous appearance of mast cells in normal mice and in congenic mast cell-deficient mice after infusion of normal bone marrow cells.

The time courses of the appearance of tissue mast cells in six sites were compared in normal WBB6F1(-)+/+ mice (+/+) and in congenic mast cell-deficient WBB6F1-W/Wv mice (W/Wv) that received an intravenous infusion of bone marrow cells from +/+ mice (BM-->W/Wv). As assessed by morphometric analysis of Carnoy's solution-fixed, methylene blue-stained tissue sections, the density of mast cells in the stomach mucosa, stomach submucosa, and spleen of +/+ mice reached maximal levels by 8 weeks of age, whereas the density of mast cells in the skin, extraparenchymal airway walls, and lung parenchyma did not reach maximal levels until 18 weeks of age. When 8-week-old W/Wv mice were infused with 2 x 10(7) bone marrow cells from /+/ mice, mast cells appeared in the stomach mucosa and submucosa after 2.5 weeks, in the spleen and extraparenchymal airway walls after 5 weeks, and in the lung parenchyma after 10 weeks. Twenty weeks after bone marrow infusion, the mast cell densities in the spleen, stomach mucosa, and stomach submucosa were seven-, 13-, and five-fold greater, respectively, than those in age-matched +/+ mice, but were eight-, two-, and five-fold lower in the skin, extraparenchymal airway walls, and lung parenchyma, respectively. Thus, those tissues that in +/+ mice reached maximal mast cell densities earlier exhibited abnormally high mast cell densities in BM-->W/Wv mice, and those that reached maximal mast cell densities later in +/+ mice had abnormally low mast cell densities in BM-->W/Wv mice. Immunological and inflammatory responses are often compared in W/Wv and BM-->W/Wv mice to assess mast cell dependency. Our results indicate that the capacity to restore a mast cell-dependent response in a particular tissue of the latter mice may relate to the local mast cell density and whether the immunological challenge activates mast cells only in that tissue or systemically with attendant widespread release of proinflammatory mediators.

Animals↗
PubMed1996

Methacholine-induced bronchoconstriction and airway smooth muscle in the guinea pig.

We examined the role of airway smooth muscle (ASM) as a determinant of the site and extent of methacholine (MCh)-induced airway narrowing in anesthetized and mechanically ventilated guinea pigs. The sites of airway narrowing and ASM were determined in animals (n = 4) bronchoconstricted to 75, 60, 40, or 15% of the maximal lung resistance (RL,max) induced by aerosolized MCh and compared with a saline-challenged animal. The median luminal area of each animal was significantly inversely correlated to the percentage of RL,max (r = -0.95; P < 0.01). However, there was no correlation between the degree of narrowing of any given airway and the quantity of ASM of any given airway. The relationship between the amount of ASM and responsiveness to MCh was studied in different animals (n = 13). The range of the concentration of MCh required to reach 50% of RL,max (EC50) varied by 254-fold, but the RL,max had only a 3.6-fold range. There was no correlation between RL,max and ASM. However, there was a correlation between the log EC50 and ASM (r = -0.541; P<0.05) in intraparenchymal cartilaginous airways. In conclusion, morphometric measurements of airway narrowing are correlated with pulmonary resistance. Variability in the quantity of ASM does not appear to be a determinant of the heterogeneity of airway narrowing or of maximal bronchoconstriction among normal guinea pigs. However, the sensitivity to MCh is associated with differences in the amount of ASM in intraparenchymal cartilaginous airways.

Airway Resistance↗
PubMed1995

Increased maximal pulmonary response to methacholine and airway smooth muscle in immature compared with mature rabbits.

We compared the effect of maturation upon the maximal pulmonary response to inhaled methacholine in rabbits and also assessed whether there was an age-related difference in the quantity of airway smooth muscle. In sedated, paralyzed, and mechanically ventilated rabbits, pulmonary resistance was measured following increasing doses of aerosolized methacholine (0.5 to 256 mg/ml). The six mature rabbits (6 mo) demonstrated a plateau in their dose-response curves whereas only three of six immature animals (1 mo) had a plateau. The immature compared with the mature animals had a greater maximal increase in pulmonary resistance (950% versus 380%). The lungs were examined by light microscopy to determine morphometrically the area of smooth muscle (ASM) in the airway walls. ASM was normalized for airway size by dividing by the ideal airway area. The normalized ASM was different for the two age groups and the immature animals' airways had more smooth muscle. The relationship between airway size and ASM was similar for the two age groups with smaller airways having proportionately more smooth muscle. The differences with age in ASM area were primarily due to the immature animals having a greater number of airways of small size. There was not a significant relationship between the maximal percent increase in pulmonary resistance and the normalized ASM. We conclude that inhaled methacholine produces a greater maximal increase in the pulmonary resistance of immature than mature rabbits and that this difference is unlikely to be caused by a proportionately greater quantity of ASM in the immature than the mature rabbit airways.

Aging↗
PubMed1993

Role of leukotriene D4 in allergen-induced increases in airway smooth muscle in the rat.

The purpose of the study was to investigate whether allergen-induced hyperresponsiveness to methacholine and an increase in airway smooth muscle (ASM) in Brown Norway (BN) rats could be mediated by LTD4, an important mediator of allergic airway responses. Male BN rats, 8 to 12 wk of age, were sensitized with ovalbumin (OA). Rats were exposed 2 wk later to aerosols of saline (n = 6), OA (n = 8), or OA after pretreatment with the LTD4 antagonist MK-571 (2 mg/kg intraperitoneally, n = 9), on six occasions at 5-day intervals. Airway responsiveness to methacholine (the concentration required to double pulmonary resistance, EC200 RL) was measured immediately before the first aerosol exposure and 2 days after the last exposure. ASM was quantitated by morphometry, and areas were standardized for size using the epithelial basement membrane length (BM). Following OA challenges EC200 RL decreased from 6.5 to 3.1 mg/ml (p < 0.05) but did not change significantly after saline or OA exposures in MK-571-pretreated animals. ASM/BM2 in the large airways was significantly greater, 3.41 +/- 0.19 x 10(-3), after OA compared with 2.35 +/- 0.22 x 10(-3) for saline exposures (p < 0.01). The ASM/BM2 after OA exposures but with MK-571 pretreatment (2.75 +/- 0.25 x 10(-3)) was intermediate in value. The results indicate that both the increase in airway responsiveness and the increase in ASM following repeated antigen exposures appear to be mediated predominantly by LTD4.

Airway Resistance↗
PubMed1992

In vivo airway reactivity: predictive value of morphological estimates of airway smooth muscle.

Airway responsiveness to methacholine and other bronchoconstrictors is highly variable within and among species. The aim of the experiments in this report was to evaluate the importance of the quantity of airway smooth muscle as a determinant of intra- and inter-species variability in airway responsiveness. To do this we established concentration-response curves to methacholine in a sample of normal guinea pigs as well as in rat, rabbit, and dog. After challenge we excised the lungs for the quantitation of smooth muscle by morphometry. Animals were anesthetized with pentobarbital and mechanically ventilated using a Harvard ventilator. Aerosols of methacholine were administered in progressively doubling concentrations from 0.0625 to 256 mg/mL for a period of 30 s for each concentration. The maximal response, determined from pulmonary resistance (RL), and the concentration of methacholine required to effect 50% of the maximal RL were determined. After provocation testing the lungs were removed and fixed with 10% Formalin. Midsagittal sections and parahilar sections were stained with hematoxylin-phloxine-saffron for microscopic examination of smooth muscle. The images of all airways in the sections were traced using a camera lucida side-arm attachment and digitized using commercial software. The area of the airway wall occupied by smooth muscle was determined and standardized for airway size by dividing it by the square of the epithelial basement membrane length. The variability in airway smooth muscle in the intraparenchymal airways was significantly greater between than within individual guinea pigs (n = 13). This was not true of extraparenchymal airways.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Comparison of upper and lower airway responses of two sensitized rat strains to inhaled antigen.

The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗