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Biomedical subjects

J A Sellers

Publications and source records attributed to J A Sellers.

13 recordsLinked to original sources
PubMed2001

Very-low-density lipoprotein assembly and secretion.

The assembly of apolipoprotein B (apoB) into VLDL is broadly divided into two steps. The first involves transfer of lipid by the microsomal triglyceride transfer protein (MTP) to apoB during translation. The second involves fusion of apoB-containing precursor particles with triglyceride droplets to form mature VLDL. ApoB and MTP are homologs of the egg yolk storage protein, lipovitellin. Homodimerization surfaces in lipovitellin are reutilized in apoB and MTP to achieve apoB-MTP interactions necessary for first step assembly. Structural modeling predicts a small lipovitellin-like lipid binding cavity in MTP and a transient lipovitellin-like cavity in apoB important for nucleation of lipid sequestration. The formation of triglyceride droplets in the endoplasmic reticulum requires MTP however, their fusion with apoB may be MTP-independent. Second step assembly is modulated by phospholipase D and A2. Phospholipases may prime membrane transport steps required for second step fusion and/or channel phospholipids into a pathway for VLDL triglyceride production. The enzymology of VLDL triglyceride synthesis is still poorly understood; however, it appears that ACAT2 is the sole source of cholesterol esters for VLDL and chylomicron assembly. VLDL production is controlled primarily at the level of presecretory degradation. Recently, it was discovered that the LDL receptor modulates VLDL production through its interactions with nascent VLDL in the secretory pathway.

Animals↗
PubMed2001

Lipoprotein assembly capacity of the mammary tumor-derived cell line C127 is due to the expression of functional microsomal triglyceride transfer protein.

C127, a murine mammary tumor-derived cell line, is capable of lipidating and secreting apolipoprotein B-41 (apoB-41) in the apparent absence of microsomal triglyceride transfer protein (MTP). Using a semiquantitative reverse transcriptase-coupled polymerase chain reaction, mouse MTP mRNA was detected in C127 cells at approximately 10-20% of the relative abundance of human MTP in HepG2 cells. Radiolabeling of C127 cells with [35S]methionine and [35S]- cysteine followed by immunoprecipitation with anti-MTP antibodies identified a band with an electrophoretic mobility identical to that of authentic mouse MTP. Cotransfection of apoB-41 and the MTP 97-kDa subunit in C127 cells enhanced apoB secretion by approximately 5-fold relative to apoB-41 transfection alone, suggesting that MTP is limiting in these cells. To establish that MTP expression is responsible for apoB-containing lipoprotein assembly in C127 cells, the effects of the MTP inhibitor BMS-200150 were examined. Secretion of apoB-41 by C127 cells was inhibited to the same extent observed in COS-1 cells cotransfected with apoB-41 and MTP. These results suggest that low MTP expression, and not the expression or overexpression of another known or novel factor(s), is responsible for apoB assembly and secretion in C127 cells and further supports the essential nature of MTP in the biogenesis of apoB-containing lipoproteins. .

Animals↗
PubMed2000

The effects of different adults as therapists during functional analyses.

The differential effects of caregivers and inpatient staff members as therapists on behavior were evaluated within a reversal design. Results indicated that problem behaviors were higher in the presence of caregivers relative to inpatient staff. These results are discussed in terms of how antecedent stimuli can affect functional analysis outcomes.

Adult↗
PubMed1997

Comparative serum estradiol profiles from a new once-a-week transdermal estradiol patch and a twice-a-week transdermal estradiol patch.

Two identical open-label, randomized crossover studies were conducted to compare serum estradiol profiles from the new 12.5- and 25-cm2 once-a-week adhesive patches with those from the 10- and 20-cm2 commercially available twice-a-week Estraderm patches when applied as directed during a 1-week patch-wear period. Both studies were conducted in healthy postmenopausal women; serum estradiol levels were determined by gas chromatography/mass spectroscopy (GC/MS). Although both sizes of both patch treatments produced mean serum estradiol levels in the therapeutic range, the once-a-week patch provided more constant mean levels, avoiding large peak-to-trough fluctuations. As expected, the differences in mean serum estradiol concentrations between the two patch treatments occurred during the second application of the twice-a-week patch. Based on these results, the once-a-week drug in adhesive patch appears to be an acceptable means of hormone replacement therapy.

Administration, Cutaneous↗
PubMed1995

A novel breath actuated device (Autohaler) consistently actuates during the early phase of inspiration.

OBJECTIVE: To establish and quantify the point during inspiration that the Autohaler (AH) inhalation system releases a metered dose of aerosol (placebo). The second objective was to determine if the Autohaler system actuates consistently, regardless of the canister life. DESIGN: Double-blind, randomized, two-period crossover, one-day trial. SETTING: Community based allergy and asthma clinic. PARTICIPANTS: Twelve patients with mild to moderate asthma. RESULTS: Mean verbal training time for the AH which included the patient demonstrating their ability to correctly use the AH was approximately 6 minutes. The mean time for actuation for the AH early in its canister life ("new canister") was 195 msec compared to 205 msec for the AH late in its canister life ("old canister") (p = 0.589). This represented the early part of inspiration as patients had a mean inspiratory duration of 2231 msec for the "new" AH and 2343 msec for the "old" AH. The mean percentage of inspiration time required to actuate the "new" AH was 8.92% compared to 8.82% for the "old" AH. Patients rated the system as easier to much easier to use compared with their current standard press and breathe inhaler. CONCLUSIONS: The AH consistently actuates early during inspiration, which is considered the optimal time for drug delivery, regardless of the canister life.

Adolescent↗