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Biomedical subjects

T Lian

Publications and source records attributed to T Lian.

8 recordsLinked to original sources
PubMed2001

Trends and developments in liposome drug delivery systems.

Since the discovery of liposomes or lipid vesicles derived from self-forming enclosed lipid bilayers upon hydration, liposome drug delivery systems have played a significant role in formulation of potent drugs to improve therapeutics. Currently, most of these liposome formulations are designed to reduce toxicity and to some extent increase accumulation at the target site(s) in a number of clinical applications. The current pharmaceutical preparations of liposome-based therapeutics stem from our understanding of lipid-drug interactions and liposome disposition mechanisms including the inhibition of rapid clearance of liposomes by controlling size, charge, and surface hydration. The insight gained from clinical use of liposome drug delivery systems can now be integrated to design liposomes targeted to tissues and cells with or without expression of target recognition molecules on liposome membranes. Enhanced safety and heightened efficacy have been achieved for a wide range of drug classes, including antitumor agents, antivirals, antifungals, antimicrobials, vaccines, and gene therapeutics. Additional refinements of biomembrane sensors and liposome delivery systems that are effective in the presence of other membrane-bound proteins in vivo may permit selective delivery of therapeutic compounds to selected intracellular target areas.

Drug Carriers↗
PubMed1999

Formulation of HIV-envelope protein with lipid vesicles expressing ganglioside GM1 associated to cholera toxin B enhances mucosal immune responses.

Taking advantage of the ability of pentameric cholera toxin B subunit (CTB) to bind selectively to GM1, we developed recently a CTB-mediated GM1 lipid vesicle delivery system to target drugs and proteins to mucosal tissues [1]. In this report, we present the use of such a strategy to deliver an HIV envelope protein (HIV-env) to mucosal tissues via intranasal route. Intranasal administration of a recombinant HIV envelope protein formulated in CTB-associated GM1 lipid vesicles enhanced mucosal IgA antibody responses detected in the nasal and gut tissues, compared to that of control animals immunized with antigen formulated in GM1-free vesicles with CTB or formulated in alum-associated vesicles with CTB. We found a nearly 2- to 3-fold enhancement in IgA antibody titers detected both in nasal and gut tissues using the CTB-GM1 lipid vesicle delivery system, compared to using the GM1-free lipid vesicle system. Intranasal administration of HIV-env formulated in the CTB-associated GM1 vesicles also induced a significant level of serum IgG and cellular immune responses against HIV-env. IgG isotype analysis indicates that CTB in GM1 vesicle delivery system enhanced both IgG1 and IgG2a while CTB in alum formulation enhanced only IgG1. However, IgA and IgG antibody responses against CTB were similar for GM1 vesicles regardless of whether HIV-env was present in the vaccine formulation. Collectively, these data indicate that delivery of HIV-env to mucosal epithelial cells with CTB-associated GM1 lipid vesicles enhanced mucosal and systemic immune responses against the HIV-envelope protein. It is possible that both the CTB-mediated targeted delivery of antigen-loaded GM1 lipid vesicles and mucosal adjuvanticity of CTB may be involved in enhancing the immune responses.

Adjuvants, Immunologic↗
PubMed1999

Thyroid testing and thyroid hormone replacement in patients with sleep disordered breathing.

The current literature recommends that patients who have symptoms of sleep disordered breathing should be evaluated for hypothyroidism. Thyroid hormone replacement therapy has been reported by some authors to be effective in treating obstructive sleep apnea in hypothyroid patients. The present study prospectively evaluated the prevalence of hypothyroidism in 1,000 consecutively presenting patients who came to the office for evaluation of snoring or obstructive sleep apnea syndrome. The authors also examined the efficacy of treatment for hypothyroidism on sleep apnea in patients with both disorders. Of the 1,000 patients, routine thyroid testing was performed on 834; only 10 of these patients (1.2%) were discovered to have previously undiagnosed clinical hypothyroidism. Four of the 10 patients with newly diagnosed clinical hypothyroidism had obstructive sleep apnea syndrome, and they received thyroid hormone replacement therapy. Once these four patients achieved a euthyroid state, repeat polysomnography showed that there was no significant difference between their pre- and posttreatment respiratory disturbance index. Based on the results of our study, we conclude the following: 1) The prevalence of hypothyroidism in patients who are evaluated for sleep disordered breathing is no greater than that of the general population. 2) Thyroid replacement therapy results in little or no improvement in sleep apnea in patients with clinical hypothyroidism. 3) Routine thyroid function screening is not indicated for patients who are being evaluated for sleep disordered breathing.

Adult↗
PubMed1997

Cholera toxin B-mediated targeting of lipid vesicles containing ganglioside GM1 to mucosal epithelial cells.

PURPOSE: To determine whether the non-toxic pentameric B subunit of Cholera toxin (CTB) binding to ganglioside GM1 on both the lipid vesicles and epithelial cells may provide a means to target lipid vesicles to mucosal cells expressing surface GM1. METHODS: Sonicated lipid vesicles containing ganglioside GM1 were prepared. Inter-vesicle cross-linking due to pentameric CTB binding to these GM1 vesicles was determined with a sub-micron particle analyzer. Association of CTB to GM1 vesicles was analyzed with continuous sucrose gradient centrifugation. CTB-mediated binding of GM1 vesicles to human mucosal epithelial cells (Caco-2 and HT-29), mucous membranes of mouse trachea, and nasal tissues were detected with fluorescent labeled vesicles. RESULTS: An increase in lipid particle size due to binding of CTB to lipid vesicles and inter-vesicles cross-linking was detected. At a 30-to-1 mole ratio of membrane-bound GM1-to-CTB, optimum increase in GM1 vesicle aggregation, was detected. Under such conditions, all the added CTB molecules were associated with GM1 vesicles. Time course analysis showed that inter-vesicles cross linking by CTB was detectable within 10 min. and reached a maximum value at 60 min. CTB associated GM1-vesicles bind to mucosal epithelial cells HT-29 and Caco-2 with similar affinity [Kd = 7.8 x 10(-4) M lipid (Caco-2) and 7.6 x 10(-4) M lipid (HT-29)]. GM1 mediated binding specificity was demonstrated by blocking with anti-GM1 antibody and the insignificant degree of CTB-associated GM1 vesicle binding to GM1 deficient C6 cells. CONCLUSIONS: The CTB-mediated GM1 binding to multiple membrane surfaces provides selective localization of GM1 vesicles to GM1 expressing mucosal cells and tissues. The strategy may be useful in localizing drugs and proteins to gut and respiratory tract mucosa.

Animals↗
PubMed1996

Allogeneic transplant of canine peripheral blood stem cells mobilized by recombinant canine hematopoietic growth factors.

We have studied graft-versus-host disease (GVHD) after transplantation of allogeneic peripheral blood stem cells (PBSC) mobilized by either recombinant canine granulocyte colony-stimulating factor (rcG-CSF) alone or combined with stem cell factor (rcSCF). These studies were prompted by the observation of extremely rapid and sustained engraftment of growth factor-mobilized PBSC in the autologous setting using genetically marked cells and changes in function of T lymphocytes from donors that had undergone mobilization. Specifically, lymphocytes from growth factor-treated donors were hyporesponsive in mixed leukocyte culture and in response to Con A, raising hopes that GVHD in dogs given growth factor mobilized allogenic PBSC might be altered in a beneficial way. Eighteen dogs were given a median of 17.1 x 10(8) PBSC/kg from littermate donors after 920 cGy of total body irradiation without postgrafting immunosuppression. Donors were either genotypically DLA-identical (n = 9) or DLA-haploidentical (n = 9). The median number of colony-forming unit-granulocyte macrophage (CFU-GM) infused was 27 x 10(4)/kg, and the number of CD34+ cells in the transplant was on the order of 4.6 x 10(6)/kg. The dogs received a median of 52.8 x 10(7) CD4 cells/kg and 13.7 X 10(7) CD8 cells/kg. All 18 dogs had prompt hematopoietic engraftment of donor cells as assessed by chimerism studies using variable number tandem repeat, as well as cytogenetic markers. Three of the nine dogs given grafts from DLA-identical littermates had fatal GVHD, five had transient GVHD, and one had no GVHD. All nine DLA-haploidentical recipients of PBSC developed fatal hyperacute GVHD. In conclusion, the expectation about rapid engraftment was fulfilled. However, incidence and severity of acute GVHD after transplantation of mobilized PBSC were not different than previously reported for nonmobilized PBSC or marrow. This model will allow for further studies, including T-cell depletion to minimize GVHD without increasing graft rejection.

Animals↗
PubMed1993

Determination of Fe-CO geometry in the subunits of carbonmonoxy hemoglobin M Boston using femtosecond infrared spectroscopy.

We have undertaken ultrafast infrared (IR) spectroscopic studies in order to elucidate the geometry of bound CO in the alpha and beta subunits of hemoglobin (Hb) M Boston 13CO. Hb M Boston is a mutant human Hb in which the distal histidine in the alpha subunits is replaced by a tyrosine. The IR absorptions of bound 13CO fall at 1925 cm-1 for the alpha subunits and 1907 cm-1 for the beta subunits. Despite a difference of nearly 20 cm-1 in these peaks, the measured anisotropies of the bound 13CO depletions following 30% photolysis are nearly identical, with values of -0.142 +/- 0.002 obtained for the alpha subunits and -0.140 +/- 0.003 obtained for the beta subunits. These translate to values of 20 degrees +/- 1 degree and 21 degrees +/- 1 degree for the values of the average angles between the CO bond and the normal to the heme planes in the alpha and beta subunits, respectively. Our present results and the work of previous investigators [Nagai, M., Yoneyama, Y., & Kitagawa, T. (1991) Biochemistry 30, 6495-6503] suggest that a change in the polar interactions of the bound CO with the heme pocket environment upon substitution of tyrosine for the distal histidine and a less bent structure for the Fe-C-O unit in the alpha subunits are responsible for the difference in the bound CO absorption frequencies in the alpha and beta subunits. A spectrum of the depletion of the bound 13CO peaks following photolysis indicates that both subunits photodissociate CO with the same quantum yield and neither subunit exhibits significant recombination within 1 ns.

Binding Sites↗
PubMed1992

[Studies of Rehmannia glutinosa Libosch. f. hueichingensis as a blood tonic].

We have studied the function of dried and prepared Rehmannia glutinosa f. hueichingensis in treating hemorrhagic anemic mice and in fostering bone marrow hematopoietic cells CFU-S, CFU-E. The results show that Rehmannia glutinosa f. hueichingensis can promote the recovery of blood deficient animals, RBC. Hb expedite the multiplication and differentiation of CFU-S, CFU-E, and thus proves markedly helpful to the generation of blood.

Anemia↗