Biomedical subjects

F Liu

Publications and source records attributed to F Liu.

At least 325 records · Page 18Linked to original sources

PubMed1999

Augmented alpha-adrenergic constriction of atherosclerotic human coronary arteries.

BACKGROUND: Although adrenergic activation plays a major role in the initiation of experimental myocardial ischemia, the significance of alpha-adrenergic coronary constriction in humans has been questioned. The present study assessed the impact of selective alpha-adrenergic receptor activation in patients with normal or atherosclerotic coronary arteries. METHODS AND RESULTS: In 39 patients, coronary blood flow (CBF, mL/min) was determined from combined angiography and Doppler measurements. In 8 patients with normal coronary arteries (group 1) and 9 with single coronary artery stenosis (group 2), doses of 1, 2.5, 5, and 10 mg IC of the alpha1-agonist methoxamine (M) were injected. Identical doses of the alpha2-agonist BHT933 (B) were injected in 8 patients with normal coronary arteries (group 3) and 8 with single stenosis (group 4). In 6 additional patients with single stenosis (group 5), aortocoronary sinus lactate differences were measured in response to M and B. CBF remained unchanged in group 1. In contrast, CBF was decreased dose-dependently in group 2, with a maximum at 10 mg M (39.0+/-9.4 versus 15.2+/-7.0). In groups 3 and 4, CBF was also decreased dose-dependently, with a maximum at 10 mg B (63.3+/-24.8 versus 49. 1+/-27.9 and 41.5+/-19.0 versus 12.7+/-8.0, respectively). In group 5, there was more net lactate production with B than with M (-0. 34+/-0.11 versus -0.04+/-0.09 mmol/L). CONCLUSIONS: In normal coronary arteries, alpha1-adrenergic activation does not reduce CBF, whereas alpha2-adrenergic activation reduces CBF by microvascular constriction. Both alpha1- and alpha2-adrenergic epicardial and microvascular constriction are augmented by atherosclerosis and can induce myocardial ischemia.

Adrenergic alpha-Agonists↗

PubMed1999

Evidence for a regulatory role of cholesterol superlattices in the hydrolytic activity of secretory phospholipase A2 in lipid membranes.

We have conducted a detailed study of the effect of membrane cholesterol content on the initial hydrolytic activity of Crotalus durissus terrificus venom phospholipase A2 (sPLA2) in large unilamellar vesicles of cholesterol/dimyristoyl-L-alpha-phosphatidylcholine (DMPC) and cholesterol/1-palmitoyl-2-oleoyl-L-alpha-phosphatidylcholine (POPC) at 37 degrees C. The activity was monitored by using the acrylodan-labeled intestinal fatty acid binding protein and HPLC. In contrast to conventional approaches, we have used small cholesterol concentration increments ( approximately 0.3-1.0 mol %) over a wide concentration range (e.g., 13-54 mol % cholesterol). In both membrane systems examined, the initial hydrolytic activity of sPLA2 is found to change with cholesterol content in an alternating manner. The activity reaches a local minimum when the membrane cholesterol content is at or near the critical cholesterol mole fractions (e.g., 14.3, 15.4, 20.0, 22.2, 25.0, 33.3, 40.0, and 50.0 mol % cholesterol) predicted for cholesterol regularly distributed in either hexagonal or centered rectangular superlattices. According to the sterol regular distribution model [Chong, P. L.-G. (1994) Proc. Natl. Acad. Sci. U.S.A. 91, 10069-10073; Liu et al. (1997) Biophys. J. 72, 2243-2254], the extent of lipid superlattices is maximal at the critical cholesterol mole fractions, at which the membrane free volume is minimal. Thus, our present data can be taken to indicate that the initial hydrolytic activity of sPLA2 is governed by the extent of cholesterol superlattice. These data provide the first functional evidence for the formation of cholesterol superlattices in both saturated (e.g., DMPC) and unsaturated (e.g., POPC) liquid-crystalline phospholipid bilayers. The data also illustrate the functional importance of cholesterol superlattice and demonstrate a new type of regulation of sPLA2. Furthermore, upon binding to cholesterol/POPC large unilamellar vesicles, the intrinsic fluorescence intensity of sPLA2 shows an alternating variation with cholesterol content, exhibiting a minimum at the critical cholesterol mole fractions. This result suggests that either the number of sPLA2 bound to lipid vesicles or the conformation of membrane-bound sPLA2 or both vary with the extent of the cholesterol superlattice in the plane of the membrane.

Binding Sites↗

PubMed1999

Primary structure, tissue distribution, and expression of mouse phosphoinositide-dependent protein kinase-1, a protein kinase that phosphorylates and activates protein kinase Czeta.

Phosphoinositide-dependent protein kinase-1 (PDK1) is a recently identified serine/threonine kinase that phosphorylates and activates Akt and p70(S6K), two downstream kinases of phosphatidylinositol 3-kinase. To further study the potential role of PDK1, we have screened a mouse liver cDNA library and identified a cDNA encoding the enzyme. The predicted mouse PDK1 (mPDK1) protein contained 559 amino acids and a COOH-terminal pleckstrin homology domain. A 7-kilobase mPDK1 mRNA was broadly expressed in mouse tissues and in embryonic cells. In the testis, a high level expression of a tissue-specific 2-kilobase transcript was also detected. Anti-mPDK1 antibody recognized multiple proteins in mouse tissues with molecular masses ranging from 60 to 180 kDa. mPDK1 phosphorylated the conserved threonine residue (Thr402) in the activation loop of protein kinase C-zeta and activated the enzyme in vitro and in cells. Our findings suggest that there may be different isoforms of mPDK1 and that the protein is an upstream kinase that activates divergent pathways downstream of phosphatidylinositol 3-kinase.

3-Phosphoinositide-Dependent Protein Kinases↗

PubMed1999

Parallel helical domains in DNA branched junctions containing 5',5' and 3',3' linkages.

The Holliday junction is a central intermediate in genetic recombination. It contains four strands of DNA that are paired into four double helical arms that flank a branch point. In the presence of Mg2+, the four arms are known to stack in pairs forming two helical domains whose orientations are antiparallel but twisted by about 60 degrees. The basis for the antiparallel orientation of the domains could be either junction structure or the effect of electrostatic repulsion between domains. To discriminate between these two possibilities, we have constructed and characterized an analogue, called a bowtie junction, in which one strand contains a 3',3' linkage at the branch point, the strand opposite it contains a 5',5' linkage, and the other two strands contain conventional 3',5' linkages. Electrostatic effects are expected to lead to an antiparallel structure in this system. We have characterized the molecule in comparison with a conventional immobile branched junction by Ferguson analysis and by observing its thermal transition profile; the two molecules behave virtually identically in these assays. Hydroxyl radical autofootprinting has been used to establish that the unusual linkages occur at the branch point and that the arms stack to form the same domains as the conventional junction. Cooper-Hagerman gel mobility analyses have been used to determine the relative orientations of the helical domains. Remarkably, we find them to be closer to parallel than to antiparallel, suggesting that the preferred structure of the branch point dominates over electrostatic repulsion. We have controlled for the number of available bonds in the branch point, for gel concentration, and for the role of divalent cations. This finding suggests that control of branch point structure alone can lead to parallel domains, which are generally consistent with recombination models derived from genetic data.

DNA↗

PubMed1999

Role of the Bicoid-related homeodomain factor Pitx1 in specifying hindlimb morphogenesis and pituitary development.

Pitx1 is a Bicoid-related homeodomain factor that exhibits preferential expression in the hindlimb, as well as expression in the developing anterior pituitary gland and first branchial arch. Here, we report that Pitx1 gene-deleted mice exhibit striking abnormalities in morphogenesis and growth of the hindlimb, resulting in a limb that exhibits structural changes in tibia and fibula as well as patterning alterations in patella and proximal tarsus, to more closely resemble the corresponding forelimb structures. Deletion of the Pitx1 locus results in decreased distal expression of the hindlimb-specific marker, the T-box factor, Tbx4. On the basis of similar expression patterns in chick, targeted misexpression of chick Pitx1 in the developing wing bud causes the resulting limb to assume altered digit number and morphogenesis, with Tbx4 induction. We hypothesize that Pitx1 serves to critically modulate morphogenesis, growth, and potential patterning of a specific hindlimb region, serving as a component of the morphological and growth distinctions in forelimb and hindlimb identity. Pitx1 gene-deleted mice also exhibit reciprocal abnormalities of two ventral and one dorsal anterior pituitary cell types, presumably on the basis of its synergistic functions with other transcription factors, and defects in the derivatives of the first branchial arch, including cleft palate, suggesting a proliferative defect in these organs analogous to that observed in the hindlimb.

Animals↗

PubMed1999

Site-specific insulin conjugates with enhanced stability and extended action profile.

Two different hydrophilic moieties, carboxyl derivatives of monosaccharidic (Glc, Gal, Man, Fuc) glycosides and methoxypolyethylene glycols of varying MW, were covalently attached to the insulin GlyA1, PheB1 and/or LysB29 amino groups (seven possible derivatives), and resulting insulin conjugates purified to homogeneity. In vivo bioactivity in rats of most derivatives was preserved while disubstituted PEG-insulins showed decreased potency. Only site-specific modification of PheB1 amino group with either moiety resulted in pronouncedly increased resistance of insulin to fibrillation, indicating that the B-chain N-terminus of the insulin molecule is mechanistically involved in the fibrillation process. Immunogenicity in vivo and in vitro of monoglycosylated insulins was comparable to that of insulin, diglycosylated insulins showed immunogenicity enhancement. Immunogenicity of PEG-insulins was significantly suppressed. PheB1-glycosylated insulins administered subcutaneously in dogs displayed extended action profiles, the most effective being PheB1-galactosylated insulin, resembling the pharmacodynamic response of intermediate-acting insulin preparations. The pharmacokinetic parameters of these insulin derivatives were not significantly different from that of insulin even though absorption and residence time and clearance were increased, providing some explanation for prolonged action profile. Lectin-specific binding as a retardation basis is not likely involved. In support of this, subcutaneously administered PheB1-PEG(600)-insulin showed an even more protracted action profile, suggesting that the basis of retardation is physical and nonspecific. This implies that by increasing PEG chain MW, further delay/prolongation of action can be achieved to yield new soluble basal insulin substitutes with potential clinical applications.

Journal Article↗

PubMed1999

Internal auditory artery infarction: clinicopathologic correlation.

OBJECTIVE: To study the pathophysiology of labyrinthine infarction. BACKGROUND: The syndrome of sudden onset vertigo or hearing loss is commonly attributed to inner ear vascular disease, yet histologic studies of isolated labyrinthine infarction in humans have been rare and have not included a complete examination of the vertebrobasilar vascular system. METHODS: Temporal bones, brainstem, cerebellum, and the supplying blood vessels were subjected to gross and microscopic postmortem examinations in a 92-year-old woman who had a sudden onset of vertigo and hearing loss in the right ear 7 years before death. RESULTS: There were prominent atherosclerotic changes at the vertebrobasilar junction, but the internal auditory artery and its branches were patent on both sides. Histologic studies showed degenerative changes in the cochlea and vestibular labyrinth on the right. The posterior canal ampulla and saccular macule were relatively preserved showing partial areas of intact sensory epithelium with underlying nerve fibers. The right vestibulocochlear nerve showed a fibrotic scar and multiple patchy areas of degeneration. These findings are most consistent with a transient period of reduced perfusion of the internal auditory artery. CONCLUSION: The partial sparing of the inferior vestibular labyrinth may indicate a decreased vulnerability to ischemia because of its better collateral blood supply.

Aged↗

PubMed1999

Hepatitis C virus but not GB virus C/hepatitis G virus has a role in type II cryoglobulinemia.

OBJECTIVE: Hepatitis C virus (HCV) infection is associated with type II cryoglobulinemia. HCV is specifically concentrated in type II cryoglobulins and has been implicated in the cutaneous vasculitis associated with the disease. In contrast to HCV, a role for hepatitis G virus (HGV) in type II cryoglobulinemia has not been defined, although prevalences as high as 43% of HGV infections in type II cryoglobulinemia have also been reported. METHODS: We studied 34 patients with type II and 29 patients with type III cryoglobulinemia associated with HCV infection, 6 patients with essential mixed cryoglobulinemia (EMC; all with type II), 50 hospital control patients, and 125 normal individuals. Serum HCV and HGV RNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). In coinfected sera, HCV and HGV were quantitated by competitive RT-PCR assays. One coinfected patient was studied longitudinally for 6 years. RESULTS: Two (5.9%) of 34 patients with HCV-infected type II cryoglobulinemia, none of 29 patients with type III cryoglobulinemia, and none of 6 patients with EMC were positive for HGV RNA, for an overall prevalence of 3.0% in mixed cryoglobulinemia. None of the control populations were positive for HGV. No statistical difference was seen between the prevalence in patients with type II cryoglobulinemia and the other populations studied. In coinfected sera, HCV, but not HGV, was concentrated in cryoglobulins, and HCV, but not HGV, correlated with cryoglobulinemia in a longitudinal study. CONCLUSION: There is a low prevalence of coinfection with HGV in patients with mixed cryoglobulinemia and HCV infection in the United States. HCV is selectively precipitated by type II cryoglobulins in coinfected sera. HGV infection does not appear to have a role in mixed cryoglobulinemia.

Adult↗

PubMed1999

Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats.

It has been shown that lipid peroxidation is associated with hepatic fibrosis and stellate cell activation. Sho-saiko-to (TJ-9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the mechanism by which TJ-9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ-9 on experimental hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pig serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ-9. Male Wistar rats were given a single intraperitoneal injection of 40 mg/kg DMN or 0.5 mL PS twice weekly for 10 weeks. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ-9, for 2 weeks before treatment or for the last 2 weeks of treatment. TJ-9 suppressed the induction of hepatic fibrosis, increased hepatic retinoids, and reduced the hepatic levels of collagen and malondialdehyde (MDA), a production of lipid peroxidation. Immunohistochemical examination showed that TJ-9 reduced the deposition of type I collagen and the number of alpha-smooth muscle actin (alpha-SMA) positive-stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoing oxidative stress, but also the production of type I collagen, alpha-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition, TJ-9 inhibited Fe2+/adenosine 5'-diphosphate-induced lipid peroxidation in rat liver mitochondria in a dose-dependent manner and showed radical scavenging activity. Among the active components of TJ-9, baicalin and baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocytes and stellate cells in vivo.

Animals↗

PubMed1999

Effects of the antihistaminergic drugs diphenhydramine and zolantidine on vestibular-induced hypothalamic neuronal activity in the guinea pig.

The mode of action of diphenhydramine in treating motion sickness is unknown. Using an electrophysiologic technique, we investigated the effects of intravenous diphenhydramine and zolantidine on the changes in neuronal activity produced by caloric stimulation in the hypothalamic paraventricular nucleus (PVN) in the guinea pig. Changes in neuronal activity were modulated by the administration of diphenhydramine in a high percentage of the neurons tested (71%), while zolantidine affected only a small number (29%). This finding reinforces the involvement of a histaminergic system in vestibular autonomic responses. The modulatory effect of diphenhydramine on PVN neuron activity may explain in part this drug's efficacy in treating motion sickness.

Animals↗

PubMed1999

Analysis of immunomodulating cytokine mRNAs in the mouse induced by mushroom polysaccharides.

The immunomodulating action of two mushroom antitumor polysaccharides, polysaccharide-protein complex (PSPC) and lentinan, was elucidated through analysing the expression profile of cytokines during a time course (0 h to 48 h) after their administration. Among the 5 cytokine genes, the induction of a marked increase in the mRNA levels of IL-1alpha, IL-1beta, TNF-alpha, IFN-gamma and M-CSF by PSPC and lentinan was observed in the peritoneal exudate cells and splenocytes. However, the time point of their increased production was different after PSPC and lentinan administration.

Adjuvants, Immunologic↗

PubMed1999

A competitive reverse transcription-polymerase chain reaction assay for quantitation of GB virus C/hepatitis G virus RNA that circumvents heteroduplex artifact.

The role of GB virus C (GBV-C)/hepatitis G virus (HGV) in hepatitis has been controversial. To investigate its possible pathogenicity and site(s) of replication, it is important to develop an accurate quantitative assay for both positive and negative strand GBV-C/HGV RNA. In this study, a competitive reverse transcription-polymerase chain reaction (RT-PCR) assay for both positive and negative strand GBV-C/HGV RNA quantitation was developed. In developing the quantitative assay, heteroduplex formation was repeatedly observed. A heterologous competitor RNA with GBV-C/HGV primer-binding sequences was introduced, and heteroduplex artifact was circumvented successfully. Two-hundred thirty-seven serum specimens were screened by RT-PCR for GBV-C/HGV RNA. Two of the 62 patients infected with chronic hepatitis C virus (HCV) were found to be positive for GBV-C/HGV RNA. None of the 50 other patients with no evidence of HCV infection and none of the 125 normal individuals were positive for GBV-C/HGV RNA. The sensitivity of RT-PCR was 3000 gE/ml (30 gE in RT-PCR). Alternate methods for residual DNA removal and its detection in synthetic RNA were introduced. A RT control containing no primer before PCR is necessary to evaluate the trace amounts of template DNA remaining in synthesized RNA. The method will differentiate reliably between positive and negative strand RNAs up to a 10(4)-fold difference in titer. The positive and negative strand GBV-C/HGV RNAs were detected in one patient by RT-PCR and hybridization analysis, and the strand titer was determined by RT-PCR.

Adult↗

PubMed1999

Differential subcellular immunolocalization of voltage-gated calcium channel alpha1 subunits in the chinchilla cristae ampullaris.

The immunohistochemical localization of alpha1A, alpha1B, alpha1C, alpha1D and alpha1E voltage-gated calcium channel subunits was investigated in the chinchilla cristae ampullaris and Scarpa's ganglia at the light and electron microscopy level with the use of specific antipeptide antibodies directed against these subunits. The stereocilia membrane of type I and type II hair cells was immunoreactive for alpha1B along its entire length. The basolateral membrane of both types of hair cells was alpha1B, alpha1C and alpha1D immunoreactive. Neurons in the Scarpa's ganglia and afferent nerve terminals in the cristae were immunoreactive for alpha1C and alpha1B. No specific immunoreactivity to alpha1A or alpha1E was seen in the sensory epithelia or ganglia. These findings are consistent with the presence of alpha1B (N-type channel), alpha1C and alpha1D (L-type channels) in the vestibular hair cells, and alpha1B (N-type channel) and alpha1C (L-type channel) in primary vestibular neurons.

Animals↗

PubMed1999

Revisiting the effectiveness of methadone treatment on crime reductions in the 1990s.

This study examines the relationship between methadone treatment and the criminal activity of 126 individuals participating in treatment during the early 1990s. The primary question addressed is to what extent is methadone maintenance treatment associated with reductions in crime? Although prior studies in the 1970s and early 1980s showed significant decreases in crime for individuals in treatment programs, criteria for remaining in this treatment modality have changed in recent years, particularly with the advent of acquired immune deficiency syndrome and the need to reduce intravenous drug use. A pre-post study design is employed spanning a 6-year time period of subject recruitment and follow-up (1987-1993). Uniform administrative records on arrests are used for the analyses. A multiple regression model is employed to explain the variance in the number of arrests 2 years following program admission, with prior criminal history, prior and current drug treatment, and current cocaine use employed as explanatory variables. Results indicate that treatment retention has only a slight, though significant, effect on reducing criminal activity during treatment. Two other factors that appear to increase arrest activity are the use of cocaine and prior criminal history. The fact that arrests did not decrease during a treatment period of 18 months on average requires more investigation in light of the increase in cocaine use in this population.

Adult↗

PubMed1999

A role for G-CSF receptor signaling in the regulation of hematopoietic cell function but not lineage commitment or differentiation.

To investigate the specificity of cytokine signals in hematopoietic differentiation, we generated mice with a targeted mutation of their G-CSF receptor (G-CSFR) such that the cytoplasmic (signaling) domain of the G-CSFR is replaced with the cytoplasmic domain of the erythropoietin receptor. In homozygous mutant mice, expression of this chimeric receptor had no apparent affect on lineage commitment and was able to support the production of morphologically mature neutrophils. However, mutant neutrophils displayed reduced chemotaxis, and G-CSF-stimulated mobilization of neutrophils and hematopoietic progenitors from the bone marrow to blood was markedly impaired. Thus, the G-CSFR is generating unique signals that are required for certain specialized hematopoietic cell functions but are not required for granulocytic differentiation or lineage commitment.

Animals↗

PubMed1999

UV cross-link mapping of the substrate-binding site of an RNase P ribozyme to a target mRNA sequence.

RNase P ribozyme cleaves an RNA helix that resembles the acceptor stem and T-stem structure of its natural ptRNA substrate. When covalently linked with a guide sequence, the ribozyme can function as a sequence-specific endonuclease and cleave any target RNA sequences that base pair with the guide sequence. Using a site-directed ultraviolet (UV) cross-linking approach, we have mapped the regions of the ribozyme that are in close proximity to a substrate that contains the mRNA sequence encoding thymidine kinase of human herpes simplex virus 1. Our data suggest that the cleavage site of the mRNA substrate is positioned at the same regions of the ribozyme that bind to the cleavage site of a ptRNA. The mRNA-binding domains include regions that interact with the acceptor stem and T-stem and in addition, regions that are unique and not in close contact with a ptRNA. Identification of the mRNA-binding site provides a foundation to study how RNase P ribozymes achieve their sequence specificity and facilitates the development of gene-targeting ribozymes.

Base Sequence↗

PubMed1999

Does remodeling occur in the diseased human saphenous vein bypass grafts? An intravascular ultrasound study.

BACKGROUND: Coronary artery remodeling is a common phenomenon in human atherosclerotic arteries. Controversies exist concerning the presence of absence of the remodeling process in diseased human coronary saphenous vein bypass grafts. The purpose of the study was to observe the vessel and lumen dimensions in patients who had undergone saphenous vein grafting with intravascular ultrasound to find out whether the remodeling process exists in the diseased human saphenous vein bypass grafts. METHODS: A total of 43 saphenous vein bypass grafts from 43 patients (39 males, 4 females, mean age 63+/-8 years); 1-16 years (mean 9.3+/-4.0 years) after grafting, who had not undergone previous catheter intervention, were studied using intravascular ultrasound. The vessel, lumen and plaque area were measured at the lesion segment as well as in the proximal and distal reference segments. The percent stenosis was calculated. RESULTS: In 43 bypass grafts having severe stenosis before intervention, plaque was eccentric in 69.4% and concentric in 30.6%. No calcification was detected in 75% cases and 25% cases has mild-moderate intimal calcification. The vessel area in the lesion segment was 19.0+/-9.7 mm2, significantly larger than the proximal reference segment 12.8+/-4.0 min2 as well as the distal reference segment 12.9+/-3.6 mm2 (p < 0.001). It was also larger than that of the average area of the proximal and distal reference segments (p < 0.001). The vessel area increased in accordance with plaque area (p < 0.001). A weak relationship existed between vessel area and percent stenosis (r = 0.37, p = 0.04). CONCLUSION: In contrary to previous findings, diseased human saphenous vein bypass grafts undergo focal compensatory enlargement (remodeling) in the presence of plaque formation. The underlying mechanism is probably similar to that in de novo atherosclerosis.

Adaptation, Physiological↗

PubMed1999

Polymer molecular weight alters properties of pH-/temperature-sensitive polymeric beads.

PURPOSE: To study the physical and release properties of different molecular weight (MW) pH- and temperature-responsive statistical terpolymers and beads of N-isopropylacrylamide (NIPAAm), butylmethacrylate (BMA) and acrylic acid (AA). METHODS: Random terpolymers of varying MW were synthesized with NIPAAm/BMA/AA of feed mol ratio 85/5/10. Polymeric beads were formed by dropping a polymer solution into an oil bath kept at a temperature above the lower critical solution temperature (LCST) of the polymer. The release profile of cytochrome c was investigated as a function of the polymer MW and pH of the release medium at 37 degrees C. RESULTS: The weight average MW ranged between 49,000 and 3 million. The LCST at pH 2.0 and pH 7.4 was 22 degrees C and 60 degrees C respectively. SEM studies showed that the size of the pores decreased as the MW increased. Irrespective of MW, the polymeric beads did not swell or dissolve at pH 2.0 and 37 degrees C and showed minimal drug release. At pH 7.4 and 37 degrees C, the rate of bead dissolution/swelling decreased as the MW of the polymer increased. CONCLUSIONS: By modulating polymer MW, it was possible to vary the physical properties of beads. Dissolution/swelling characteristics were dependent on the MW of the polymer. Such unique dissolution/swelling properties are useful for delivering drugs to different sites in the intestine.

Acrylates↗