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Biomedical subjects

S M Sullivan

Publications and source records attributed to S M Sullivan.

54 records · Page 3Linked to original sources
PubMed1992

Inhibition of human immunodeficiency virus-1 proliferation by liposome-encapsulated sense DNA to the 5' tat splice acceptor site.

A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.

Antiviral Agents↗
PubMed1991

The treatment of temporomandibular joint internal derangements using a modified open condylotomy: a preliminary report.

A modified open condylotomy was used to treat 44 patients who presented with painful temporomandibular joints, and in whom the clinical and arthrographic findings were indicative of disc displacement. A total of 64 joints (20 bilateral) were operated on. Postoperatively, the patients showed an overall improvement in their functional symptoms. Ninety-one percent of patients had improvement in clicking and popping, and 96% reported decrease in locking. Complaints related to pain and headache were improved 85% and 95%, respectively. The modified technique, as well as the anatomic basis for its use, are discussed.

Adolescent↗
PubMed1991

Capillary spatial pattern and muscle fiber geometry in three hamster striated muscles.

Since most oxygen exchange in muscle is thought to occur by diffusion across the walls of capillaries, it is important to determine the spatial relationship between capillaries and muscle fibers. We have extended the work of Kayar et al. (Microvasc. Res 24: 326-341, 1982) to include other statistical tests that allow one to make stronger statements regarding the spatial pattern. Data for hamsters were obtained from two sartorius, three retractor, and five soleus muscle sections. Distances between all pairs of capillaries, distances between a capillary and its first nearest neighbor for all capillaries, and distances between random tissue sample points and the closest capillary were used to test the spatial arrangement of capillaries. The null hypothesis tested of complete spatial randomness of capillary locations was rejected in favor of a regular alternative in one each of the sartorius and retractor fields and in all five soleus fields. We formulated a geometric model, composed of a space-filling array of identical hexagonal muscle fibers with capillaries placed randomly at the juncture of three fibers or between two fibers, according to the observed relative probability of those occurrences. The model simulations of muscle fibers and capillaries were then analyzed by the same statistical tests used on the histological sections. The findings were similar in both cases, providing confidence that the assumptions of the model were sufficient approximations. The results of this study provide a basis for the placement of capillaries around muscle fibers in mathematical models of oxygen transport in capillary networks.

Animals↗
PubMed1989

Effect of cholesterol on the uptake and intracellular degradation of liposomes by liver and spleen; a combined biochemical and gamma-ray perturbed angular correlation study.

We investigated the effect of cholesterol on the uptake and intracellular degradation of liposomes by rat liver and spleen macrophages. Multilamellar vesicles (MLV) consisting of distearoylphosphatidylcholine/phosphatidylserine (molar ratio 9:1) or distearoylphosphatidylcholine/cholesterol/phosphatidylserine (molar ratio 4:5:1) were labeled with [3H]cholesteryl hexadecyl ether and/or cholesteryl [14C]oleate. After i.v. injection the cholesterol-containing liposomes were eliminated less rapidly from the bloodstream and taken up to a lesser extent by the liver (macrophages) than the cholesterol-free liposomes. Assessment of the 3H/14C ratios in liver and spleen cells revealed that the cholesterol-containing liposomes are substantially more resistant towards intracellular degradation than the cholesterol-free liposomes. These results could be confirmed by measuring the release of 111In from liposomes after uptake by liver and spleen by means of gamma-ray perturbed angular correlation spectroscopy. Experiments with cultured Kupffer cells in monolayer also revealed that incorporation of cholesterol results in a decrease of the uptake and an increase of the intracellular stability of cholesteryl [14C]oleate-labeled liposomes. Finally, incubation of both types of liposomes with lysosomal fractions prepared from rat liver demonstrated a difference in susceptibility to lysosomal degradation: the cholesterol-free vesicles were much more sensitive to lysosomal esterase than the cholesterol-containing liposomes. These results may be relevant to the application of liposomes as a drug carrier system to liver and spleen (macrophages).

Animals↗
PubMed1989

Capillary spatial pattern and muscle fiber geometry in three hamster striated muscles.

The primary goal of this project was to elucidate the spatial pattern of capillaries in three hamster striated muscles according to statistical techniques of pattern analysis. The spatial pattern of capillaries and traditional measures of capillarity are important to understanding the supply and distribution of oxygen and nutrients in a tissue. Statistical tests based on the distance between nearest neighbor capillaries are the most sensitive for detecting regularity in a pattern. A mathematical model was created to simulate the observed muscle fields. The same statistical tests that were performed on the empirical data were performed on the modelled data. The results of the analysis of the modelled data agree sufficiently with those of the empirical data to justify overall confidence in the assumptions. Conclusions that may be drawn from this investigation are (1) the spatial pattern of capillaries tends to be more regular than random and never was there evidence for aggregation using the test statistics; (2) as many as 60-75% of capillaries are located at the corners of muscle fibers indicating that there is some preferential placement for capillaries, and (3) the model developed is a good first approximation to the real situation.

Animals↗
PubMed1987

Relationship between mitochondrial volume density and capillarity in hamster muscles.

Mitochondrial volume density and lipid droplet-volume density were stereologically determined from electron micrographs of muscle fibers from three hamster muscles: retractor, sartorius, and soleus. The number of capillaries around a fiber, length of capillary-fiber contact, and muscle fiber area were also measured. Glycolytic fibers of the retractor and sartorius had larger cross-sectional areas, lower mitochondrial-volume densities, fewer subsarcolemmal aggregates of mitochondria, and lower capillary-fiber contact length in comparison to oxidative fibers of the retractor and soleus. Values for mitochondrial volume density in the different muscles correlated well (r = 0.97) with resting O2 consumption. The mitochondrial volume densities for each muscle correlated well (r = 0.99) with O2 diffusion coefficients of these muscles. Our results indicate that an analysis of the adequacy of O2 supply to an individual muscle fiber must take into account an interplay among fiber size, percent of the muscle fiber perimeter in contact with a capillary (capillary-fiber contact), and O2 demand of the fiber estimated by mitochondrial volume density.

Animals↗
PubMed1986

Electrophysiologic evaluation of pirmenol for sustained ventricular tachycardia secondary to coronary artery disease.

The efficacy and electrophysiologic effects of pirmenol were evaluated in 21 patients with a history of sustained ventricular tachycardia (VT) and coronary artery disease. Intravenous pirmenol (0.7- to 1.1-mg/kg bolus, followed by a 35- to 40-micrograms/kg/min infusion) significantly prolonged the PR, QRS, QT and corrected QT intervals, HV interval and right ventricular effective refractory period, and shortened the sinus cycle length and atrioventricular nodal block cycle length. All 21 patients had inducible VT (20 sustained, 1 nonsustained) during programmed stimulation in the control state. After intravenous pirmenol, 5 patients (24%) no longer had inducible VT. In those in whom VT was still inducible, the VT cycle length was prolonged significantly. The 5 patients who responded to intravenous pirmenol were given oral pirmenol (200 to 250 mg every 8 hours) for 1 to 3 days and retested with programmed stimulation. In 4 of these 5, VT could not be induced with oral pirmenol administration; in 1 patient sustained VT was induced and pirmenol therapy was discontinued. Oral pirmenol suppressed recurrent VT during a follow-up of 315 +/- 133 days in 4 patients. However, pirmenol therapy was discontinued in 2 patients because of possible deleterious effects (worsened heart failure in 1 patient and elevated liver function test results in 1). Thus, pirmenol, a type IA antiarrhythmic drug, had an overall efficacy of approximately 19% in patients with sustained VT secondary to coronary artery disease.

Adult↗
PubMed1986

Enhanced delivery to target cells by heat-sensitive immunoliposomes.

Heat-sensitive immunoliposomes are capable of releasing the entrapped content at the target cell surface upon a brief heating to the phase transition temperature of the liposome membrane. In this study we have examined the delivery efficiency of drugs entrapped in heat-sensitive immunoliposomes. Immunoliposomes composed of dipalmitoyl phosphatidylcholine with entrapped [3H]uridine were incubated with target cells at 4 degrees C. The cell-liposome mixture was then heated to 41 degrees C and the uptake of [3H]uridine into the intracellular pool of phosphorylated uridine-containing molecules was measured. The immunoliposomes showed maximal release of the uridine at 41 degrees C, the phase transition temperature of dipalmitoyl phosphatidylcholine liposomes. The largest accumulation of [3H]uridine in the target cells also took place at 41 degrees C. The initial level of uptake of [3H]uridine released from immunoliposomes by heating was greatly enhanced over that observed for free [3H]uridine and [3H]uridine released from liposomes without attached antibody. The nucleoside uptake inhibitors nitrothiobenzylinosine, dipyridamole, and unlabeled uridine were able to inhibit uptake of [3H]uridine released from immunoliposomes. This supports the hypothesis that the enhanced uptake is due to a heat-induced release of [3H]uridine at the cell surface followed by transport and phosphorylation of [3H]uridine by the target cells. These results indicate the feasibility of using the heat-sensitive immunoliposomes as a target-specific drug delivery system.

Animals↗
PubMed1985

Preparation and characterization of heat-sensitive immunoliposomes.

Immunoliposomes able to bind specifically to target cells and to release their encapsulated contents upon brief heating were prepared. Monoclonal anti-H2Kk was covalently derivatized with palmitic acid by the method of Huang, A. et al. (Huang, A., Tsao, Y.S., Kennel, S.J. and Huang, L. (1982) Biochim. Biophys. Acta 716, 140-150). The palmitoyl antibody was injected at a controlled rate into a suspension of fused unilamellar dipalmitoylphosphatidylcholine liposomes maintained at a constant temperature. The final protein-to-lipid ratio of the resultant liposomes with incorporated antibody (immunoliposomes) was dependent upon the rate of antibody injection and the lipid concentration. Injection of palmitoyl antibody into a liposome suspension containing 50 mM carboxyfluorescein at 41 degrees C resulted in simultaneous antibody incorporation and entrapment of dye. Immunoliposomes were able to release the entrapped carboxyfluorescein upon heating. The release of dye at temperatures between the pre- and main-transition temperatures of DPPC was abolished by the addition of calf serum (5%). Furthermore, the presence of serum resulted in an increase in the temperature of the maximal release rate and also in the rate of release at that temperature. Retention of antigen-binding capacity was demonstrated by the ability of the immunoliposomes to bind specifically to the target cells. Rapid release of entrapped carboxyfluorescein from immunoliposomes bound to target cells at 4 degrees C was achieved upon brief exposure (less than 3 min) at 41 degrees C. These heat-sensitive immunoliposomes may be useful in enhancing drug delivery to target cells.

Animals↗
PubMed1984

In vitro O2 uptake and histochemical fiber type of resting hamster muscles.

In vitro oxygen consumption (VO2), histochemical fiber type, capillary arrangement, and muscle fiber geometry were measured in three hamster striated muscles. These muscles varied markedly in their histochemical fiber type composition (% by number): retractor (70% FG, fast-twitch, glycolytic; 16% FOG, fast-twitch, oxidative-glycolytic; 14% SO, slow-twitch, oxidative); soleus (57% FOG, 43% SO), and sartorius (98% FG, 2% FOG). Sartorius VO2 [0.80 +/- 0.034 (SE) ml O2 X min-1 X 100 g-1] was significantly different (P less than 0.01) from VO2 of retractor (0.89 +/- 0.038) and soleus (1.00 +/- 0.048). The number of capillaries around a fiber and the surface area/volume were greater for FOG and SO fibers than for FG fibers. Fibers of all types appeared to be roughly elliptical in shape. Capillaries were uniformly distributed around fibers in the soleus, but they were located more toward the ends of the major diameter in the retractor and sartorius. The results suggest a relationship among a fiber's oxidative capacity (based on its histochemical staining pattern), number of surrounding capillaries and surface area/volume. Furthermore, results suggest that VO2 and capillary spacing around a fiber may depend on fiber type.

Adenosine Triphosphatases↗
PubMed1981

Effect of oxygen on arteriolar dimensions and blood flow in cat sartorius muscle.

The effect of O2 on arteriolar internal diameter, dual-slit velocity, and volume flow was studied by intravital microscopy in isolated autoperfused cat sartorius muscle. The muscle surface was covered with silicone oil, and gas mixtures containing 0, 5, 10, or 20% O2 in N2 were introduced over the muscle. When the O2 concentration was increased from 0 to 10%, arteriolar diameter, dual-slit velocity, and volume flow decreased on the average by 11 +/- 4, 30 +/- 29, and 37 +/- 13%, respectively. Under 20% O2, these parameters decrease by an additional 9 +/- 5, 29 +/- 10, and 30 +/- 14%, respectively. Percentage reduction in the diameter of large and small arterioles located at the same depth in the muscle were not significantly different. Conversely, the fall in volume flow was significantly greater in small arterioles. The lesser flow decrease in large vessels may reflect the fact that large vessels also feed deep muscle layers where the change in tissue O2 tension (PO2) is less. Our results do not support the hypothesis that small arterioles are intrinsically more sensitive to changes in tissue PO2.

Animals↗
PubMed1981

Effect of oxygen on blood flow autoregulation in cat sartorius muscle.

To assess the role of O2 in blood flow autoregulation, arteriolar diameter and erythrocyte velocity were measured in individual microvessels of the cat sartorius muscle while ambient O2 tension (PO2) and perfusion pressure were altered. The muscle surface was covered with a layer of silicone fluid equilibrated with a gas mixture containing 0--20% O2. Under control conditions (0% O2) all except the largest arterioles dilated with pressure reduction, and all showed significant blood flow autoregulation. Elevated PO2 diminished flow regulation and dilation in large and small arterioles when arterial pressure was reduced. This effect was generally more pronounced in the small arterioles where elevated PO2 caused complete cessation of blood flow. Complete blood flow stoppage was not routinely seen in larger vessels and may reflect the fact that these vessels also supply deeper tissue regions less affected by the change in ambient PO2. Our results indicate that the PO2 level of the tissue may be an important determinant in blood flow autoregulation.

Adaptation, Physiological↗
PubMedDate not supplied

Orthognathic surgery.

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Facial Asymmetry↗
PubMedDate not supplied

Regeneration of peri-implant infrabony defects using PerioGlas: a pilot study in rabbits.

PerioGlas is a silicate-based synthetic bone augmentation material that has been used to fill periodontal defects with bonding and integration to both soft tissue and bone. The purpose of this research was to determine the PerioGlas interface with titanium dental implants and bone. Seven live rabbits were used; however, one rabbit was euthanized at 3 days as a result of a tibial fracture through the implant placement site. Each rabbit received four 3.3 x 8 mm Imtec titanium plasma-sprayed dental implants, two in each proximal tibia. One implant in each rabbit was placed in the standard fashion. Two implants in each rabbit had a surgically created defect adjacent to one side of the coronal aspect of the implant. The defect was subsequently filled with PerioGlas. One implant in each rabbit had a surgically created defect that was not filled with PerioGlas. The rabbits were sacrificed at 1, 2, 3, 6, 12, and 24 weeks. Each specimen was prepared for histologic viewing, yielding a nondecalcified specimen demonstrating the interface of bone, implant, and PerioGlas. The results demonstrate peripheral formation of osteoid, followed by bone deposition within the defect from host (surgical margin) bone, toward the implant. The new osteoid and bone form around the PerioGlas particles. Newly formed trabeculae connect these areas of osteoid and new bone around the PerioGlas, interconnecting the PerioGlas particles. The new bone eventually reaches the implant, and osseointegration occurs with incorporation of the PerioGlas particles.

Animals↗