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Mimi L K Tang

Publications and source records attributed to Mimi L K Tang.

16 recordsLinked to original sources
PubMed2006

The effects of relaxin and estrogen deficiency on collagen deposition and hypertrophy of nonreproductive organs.

In this study, we determined the effects of relaxin and estrogen deficiency and estrogen replacement therapy (ERT) on the cardiac, renal, and pulmonary phenotypes of female relaxin gene knockout (Rln1-/-) and age-matched wild-type (Rln1+/+) mice. One-month-old Rln1+/+ and Rln1-/- mice were bilaterally ovariectomized or sham-operated and aged until 9 or 12 months. A subgroup of ovariectomized mice received ERT from 9 to 12 months of age. At the appropriate time points, heart, kidney, and lung tissues from these mice were collected and analyzed for changes in organ fibrosis, hypertrophy, and airway thickening. Neither ovariectomy nor ERT had any effect on cardiac or renal collagen concentration in all groups studied. In contrast, total lung collagen concentration and airway subepithelial collagen deposition were significantly increased in ovariectomized Rln1+/+ mice (P<0.05 vs. sham) and to a greater extent in ovariectomized Rln1-/- mice (P<0.01 vs. sham). Ovariectomy of Rln1+/+ mice also led to a significant increase in airway smooth muscle (SM) (lung) thickening, which was further exaggerated in Rln1-/- mice. Cardiac hypertrophy, evidenced by increased heart weight and expression of hypertrophy-related genes (all P<0.05 vs. sham) was only observed in Rln1-/- mice. These findings demonstrated an increased pathology in mice that were deficient of both relaxin and estrogen. ERT significantly decreased airway fibrosis, airway SM thickening, and cardiac hypertrophy when administered to ovariectomized Rln1-/- mice (all P<0.05 vs. ovariectomy alone). These findings suggest that relaxin and estrogen appear to play protective roles against airway fibrosis, airway SM thickening, and cardiac hypertrophy in female mice.

Actins↗
PubMed2006

Airway remodelling in asthma: current understanding and implications for future therapies.

Airway remodelling refers to the structural changes that occur in the airway wall in asthma. These include epithelial hyperplasia and metaplasia, subepithelial fibrosis, muscle cell hyperplasia and angiogenesis. These structural changes result in thickening of the airway wall, airway hyperresponsiveness (AHR), and a progressive irreversible loss of lung function. The precise sequence of events that take place during the remodelling process and the mechanisms regulating these changes remain poorly understood. It is thought that airway remodelling is initiated and promoted by repeated episodes of allergic inflammation that damage the surface epithelium of the airway. However, other mechanisms are also likely to contribute to this process. Moreover, the interrelationship between airway remodelling, inflammation and AHR has not been clearly defined. Currently, there are no effective treatments that halt or reverse the changes of airway remodelling and its effects on lung function. Glucocorticoids have been unable to eliminate the progression of remodelling changes and there is limited evidence of a beneficial effect from other available therapies. The search for novel therapies that can directly target individual components of the remodelling process should be made a priority. In this review, we describe the current understanding of the airway remodelling process and the mechanisms regulating its development. The impact of currently available asthma therapies on airway remodelling is also discussed.

Adrenergic beta-Agonists↗
PubMed2006

Probiotic use in clinical practice: what are the risks?

Probiotics have been advocated for the prevention and treatment of a wide range of diseases, and there is strong evidence for their efficacy in some clinical scenarios. Probiotics are now widely used in many countries by consumers and in clinical practice. Given the increasingly widespread use of probiotics, a thorough understanding of their risks and benefits is imperative. In this article we review the safety of probiotics and discuss areas of uncertainty regarding their use. Although probiotics have an excellent overall safety record, they should be used with caution in certain patient groups-particularly neonates born prematurely or with immune deficiency. Because of the paucity of information regarding the mechanisms through which probiotics act, appropriate administrative regimens, and probiotic interactions, further investigation is needed in these areas. Finally, note that the properties of different probiotic species vary and can be strain-specific. Therefore, the effects of one probiotic strain should not be generalized to others without confirmation in separate studies. Careful consideration should be given to these issues before patients are advised to use probiotic supplements in clinical practice.

Adult↗
PubMed2005

Endogenous relaxin regulates collagen deposition in an animal model of allergic airway disease.

We examined the relationship among relaxin (a peptide hormone that stimulates collagen degradation), airway fibrosis, other changes of airway remodeling, and airway hyperresponsiveness (AHR) in an animal model of allergic airway disease. Eight- to 10-wk-old relaxin gene-knockout (RLX(-/-)) and wild-type (RLX(+/+)) mice were sensitized with ovalbumin (OVA) or saline ip at d 0 and 14 and challenged three times per week for 6 wk with nebulized 2.5% OVA or saline. Saline-treated control RLX(+/+) and RLX(-/-) mice had equivalent collagen expression and baseline airway responses. OVA-treated RLX(-/-) mice developed airway inflammation equivalent to that in OVA-treated RLX(+/+) mice. However, OVA-treated RLX(-/-) mice had markedly increased lung collagen deposition as compared with OVA-treated RLX(+/+) and saline-treated mice (all P < 0.05). Collagen was predominantly deposited in the subepithelial basement membrane region and submucosal regions in both OVA-treated RLX(+/+) and RLX(-/-) mice. The increased collagen measured in OVA-treated RLX(-/-) mice was associated with reduced matrix metalloproteinase (MMP)-9 (P < 0.02) expression and failure to up-regulate matrix metalloproteinase-2 expression, compared with levels in OVA-treated RLX(+/+) mice. Goblet cell numbers were equivalent in OVA-treated RLX(-/-) and RLX(+/+) mice and increased, compared with saline-treated animals. Both OVA-treated RLX(+/+) and RLX(-/-) mice developed similar degrees of AHR after OVA treatment. These findings demonstrate a critical role for relaxin in the inhibition of lung collagen deposition during an allergic inflammatory response. Increased deposition of collagen per se did not influence airway epithelial structure or AHR.

Animals↗
PubMed2005

The Australasian Society of Clinical Immunology and Allergy position statement: Summary of allergy prevention in children.

A family history of allergy and asthma identifies children at high risk of allergic disease. Dietary restrictions in pregnancy are not recommended. Avoiding inhalant allergens during pregnancy has not been shown to reduce allergic disease, and is not recommended. Breastfeeding should be recommended because of other beneficial effects, but if breast feeding is not possible, a hydrolysed formula is recommended (rather than conventional cow's milk formulas) in high-risk infants only. Maternal dietary restrictions during breastfeeding are not recommended. Soy formulas and other formulas (eg, goat's milk) are not recommended for reducing food allergy risk. Complementary foods (including normal cow's milk formulas) should be delayed until a child is aged at least 4-6 months, but a preventive effect from this measure has only been demonstrated in high-risk infants. There is no evidence that an elimination diet after age 4-6 months has a protective effect, although this needs additional investigation. Further research is needed to determine the relationship between house dust mite exposure at an early age and the development of sensitisation and disease; no recommendation can yet be made about avoidance measures for preventing allergic disease. No recommendations can be made about exposure to pets in early life and the development of allergic disease. If a family already has pets it is not necessary to remove them, unless the child develops evidence of pet allergy (as assessed by an allergy specialist). Women should be advised not to smoke while pregnant, and parents should be advised not to smoke. No recommendations can be made on the use of probiotic supplements (or other microbial agents) for preventing allergic disease at this time. Immunotherapy may be considered as a treatment option for children with allergic rhinitis, and may prevent the subsequent development of asthma.

Air Pollution, Indoor↗
PubMed2005

Results of a Phase I study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children with Stage 4 neuroblastoma.

BACKGROUND: A Phase I study of 11 pediatric patients with newly diagnosed, Stage 4 neuroblastoma was conducted using monocyte-derived dendritic cells (DC) pulsed with tumor RNA to produce antitumor vaccines (DC(RNA)). METHODS: Patients received two courses of induction with carboplatin followed by standard chemotherapy, surgery, radiation, high-dose therapy, stem cell rescue, and DC(RNA) vaccine therapy. RESULTS: The results showed that this method for producing and administering DC(RNA) from a single leukapheresis product was both feasible and safe in this pediatric neuroblastoma population. Two courses of carboplatin maintained lymphocyte counts at normal levels. However, immune function 6 weeks after high-dose chemotherapy and stem cell rescue and prior to receiving DC(RNA) was impaired in all patients tested. There was an alteration in the ratio of CD4-positive and CD80-positive T cells. CD4-positive cell numbers were below normal, whereas CD8-positive cell numbers were above normal for all patients. In addition, CD19-positive cell numbers were below normal for all but one patient. It was found that humoral responses to recall antigens (diphtheria and tetanus) and cellular responses to mitogen and recall antigens were below normal in most patients. Despite this, two of three patients tested showed a tumor-specific humoral immune response to DC(RNA). Among the patients who had measurable disease at the time of DC(RNA) vaccine, none showed any objective tumor response. CONCLUSIONS: DC(RNA) vaccines were both safe and feasible in children with Stage 4 neuroblastoma. Humoral responses to tumor were detected, although remained immunosuppressed at the time of administration, limiting efficacy.

Adrenal Gland Neoplasms↗
PubMed2005

Optimising the management of allergic rhinitis: an Australian perspective.

Allergic rhinitis (AR) is one of the most prevalent medical conditions. It has significant effects on quality of life and can have considerable socioeconomic effects. The traditional classification of perennial and seasonal rhinitis does not distinguish between provoking factors, nor does it indicate the most appropriate treatment. A more useful classification is based on symptoms, which may be intermittent or persistent, and vary widely in severity. The goal of management is to achieve optimal symptom control. Therapeutic options include allergen avoidance, pharmacotherapy and immunotherapy. Antihistamines and intranasal corticosteroids (INCS) have become the cornerstones of therapy. A variety of effective treatments are available for consumers to self-select, without the advice of a doctor or pharmacist. INCS are widely recognised as the most effective pharmacotherapy for AR, in both adults and children. The efficacy of various preparations is similar, but those with low systemic bioavailability are preferred for children and for patients who are also receiving inhaled, topical or systemic corticosteroids.

Adolescent↗
PubMed2005

The development of food allergy after liver transplantation.

The acquisition of new food allergy after orthotopic liver transplantation is now a well described phenomenon, mainly reported in children. The etiology of this phenomenon is at present unclear, but has been ascribed by some to tacrolimus treatment. Here we report a case of liver transplant acquired food allergy (LTAFA) in a child who received a split liver graft. The case is remarkable for the absence of new food allergy in the adult recipient of the same graft. This suggests that host-specific factors play an important role in the development of food allergy after liver transplantation, and emphasizes the predisposition that children have toward this phenomenon. Possible mechanisms underlying the development of food allergy after liver transplantation are discussed. In conclusion, tacrolimus treatment alone cannot account for LTAFA. Host factors such as the maturity of immune regulatory mechanisms are likely to play a critical role in the development of new food allergy after a liver transplant.

Adult↗
PubMed2005

Hereditary angio-oedema in children: a management guideline.

Hereditary angio-oedema is an uncommon condition, which usually first presents in childhood. In the absence of appropriate treatment hereditary angio-oedema has a high mortality. There are a number of reports of successful short- and long-term treatment with individual agents in those who suffer from hereditary angio-oedema. However, there is little guidance in the literature for the overall management of children and adolescents with this condition. Here we review the treatment options available for children and adolescents with hereditary angio-oedema, and propose a simple management guideline for such patients.

Adolescent↗
PubMed2005

Investigating the role of relaxin in the regulation of airway fibrosis in animal models of acute and chronic allergic airway disease.

Airway remodeling is a characteristic feature of asthma that leads to chronic irreversible airway obstruction. Fibrosis in the basement membrane region is a hallmark of remodeling in asthma that is not found in other diseases. In the outlined studies, we investigated the relationship between relaxin and airway fibrosis in asthma using acute and chronic models of allergic airway disease. These studies confirm a critical role for relaxin, in the regulation of collagen deposition in the airway/lung in animal models of allergic airway disease.

Acute Disease↗
PubMed2004

Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer.

We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony-stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intradermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis.

Adolescent↗
PubMed2002

Relaxin deficiency in mice is associated with an age-related progression of pulmonary fibrosis.

Relaxin (RLX) is a peptide hormone with known antifibrotic properties. However, its significance in the lung and its role as a therapeutic agent against diseases characterized by pulmonary fibrosis are yet to be established. In this study, we examined age-related structural and functional changes in the lung of relaxin-deficient mice. Lung tissues of male and female RLX knockout (-/-) and RLX wild-type (+/+) mice at various ages were analyzed for changes in collagen expression and content. We demonstrate an age-related progression of lung fibrosis in RLX -/- mice with significantly increased tissue wet weight, collagen content and concentration, alveolar congestion, and bronchiole epithelium thickening. The increased fibrosis was associated with significantly altered peak expiratory flow and lung recoil (lung function) in RLX -/- mice. Treatment of RLX -/- mice with relaxin in early and developed stages of fibrosis resulted in the reversal of collagen deposition. Organ bath studies showed that precontracted lung strips relaxed in the presence of relaxin. Together, these data indicate that relaxin may provide a means to regulate excessive collagen deposition in diseased states characterized by pulmonary fibrosis.

Aging↗
PubMed2002

Is prevention of childhood asthma possible? Allergens, infections and animals.

What we know: Epidemiological studies have identified a number of factors associated with increased incidence of asthma. These include allergen sensitisation and exposure, reduced exposure to infections and to farm animals in early childhood, and maternal smoking. These factors may represent "true" risk factors for asthma or may be merely associated factors that do not in themselves cause asthma. The "hygiene hypothesis" has been proposed as one mechanism by which infections may protect against asthma. Current recommendations for the primary prevention of asthma include exclusive breastfeeding for the first six months of life, avoidance of maternal smoking during pregnancy and infancy, and reducing the levels of house-dust mite in some environments. What we need to know: What are the mechanisms by which specific risk factors and prevention strategies lead to or protect from asthma? How do genetic and environmental factors interact to increase the risk of asthma?

Allergens↗
PubMed2002

Mobilization of dendritic cells in cancer patients treated with granulocyte colony-stimulating factor and chemotherapy.

The number of dendritic cells (DC) circulating in the peripheral blood of cancer patients were monitored at multiple time points during chemotherapy and granulocyte colony-stimulating factor (G-CSF) support. DC were identified via the lack of expression of standard lineage markers and high expression of HLA-DR (LN-/DR+). The expression of DC-associated markers, including CD83, CD11c, IL-3Ralpha (CDw123) and CD86, within this LN-/DR+ population was also monitored. Maximal mobilization occurred during recovery on d 12, with a mean 32-fold increase in LN-/DR+ numbers. The most striking increase was observed in the LN-/DR+/CD83+ cell population: 12 d after commencement of treatment, the proportion of these cells had increased by approximately 120-fold when compared with baseline. Peripheral blood mononuclear cell (PBMC) and CD34+ cell numbers also peaked 12 d into the treatment regimen in most patients. These data suggest that it should be possible to acquire substantial numbers of DC from leukapheresis products collected from cancer patients undergoing a standard treatment regimen of chemotherapy and G-CSF. This strategy may be a feasible, low-risk means of acquiring cells for DC-based vaccine studies.

Antigens, CD34↗
PubMed2002

Polyclonal and allergen-induced cytokine responses in adults with asthma: resolution of asthma is associated with normalization of IFN-gamma responses.

BACKGROUND: Atopic disease is associated with skewing of immune responses away from a T(H)1 toward a T(H)2 profile. Previous studies have implicated this cytokine imbalance in the development of disease. However, it is not known whether normalization of this imbalance is conversely associated with disease resolution. OBJECTIVE: To further delineate the role of reduced T(H)1 and increased T(H)2 cytokine production in the pathogenesis of atopic disease and to determine whether disease resolution is associated with alteration of cytokine profiles, we investigated cytokine responses in a cohort of adult patients with asthma followed from childhood. METHODS: A cohort of wheezy children and control subjects aged 7 to 10 years were recruited from 1964 to 1967. Subjects were reevaluated every 7 years to monitor the outcome of childhood asthma. At the 42-year follow-up, 89 subjects from this cohort were evaluated for mitogen and house dust mite (HDM)-induced T(H)1 (IFN-gamma) and T(H)2 (IL-4, IL-5, and IL-13) cytokine responses. Cytokine responses were compared in patients with ongoing asthma, patients with resolved asthma, and control subjects. RESULTS: Patients with severe ongoing asthma had significantly reduced HDM-induced IFN-gamma production compared with that of control subjects and patients with resolved asthma. In contrast, HDM-induced IFN-gamma production in patients with resolved asthma was equivalent to that seen in control subjects. Patients with ongoing and resolved asthma produced significantly higher levels of IL-5 in response to HDM compared with that seen in control subjects, with levels being equivalent in patients with active and resolved asthma. HDM-induced IL-13 production was significantly increased in the patients with resolved asthma when compared with that seen in the control subjects. PHA-induced cytokine responses did not parallel HDM-induced responses. CONCLUSION: Patients with persistent and severe atopic asthma have a reduced HDM-induced T(H)1 response, whereas those with resolved asthma do not. This suggests that reduced HDM-induced IFN-gamma production might be an important factor contributing to ongoing severe asthma and that normalization of allergen-induced T(H)1 responses might be important for disease resolution. The finding that all subjects with a history of asthma displayed increased HDM-induced T(H)2 (IL-5 and IL-13) cytokine responses, irrespective of the presence or absence of asthma, suggests that increased T(H)2 responses reflect the presence of the atopic state per se rather than being specifically linked to asthma.

Adult↗