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Biomedical subjects

D Collins

Publications and source records attributed to D Collins.

At least 19 recordsLinked to original sources
PubMed1998

Vitamin D and bone mineral density.

Bone mineral density (BMD) at the lumbar spine and the neck of femur and serum concentrations of 25-hydroxyvitamin D (25OHD), intact parathyroid hormone (PTH), alkaline phosphatase, calcium, albumin, creatinine and phosphate were measured in a group of 166 postmenopausal women (30-79 years) attending a bone clinic for bone density measurements. Four subjects with suspected primary hyperparathyroidism were excluded from analysis. BMD at the lumbar spine was correlated with body mass index (BMI) (r = 0.278, p = 0.0003), age (r = -0.194, p = 0.0134) and serum 25OHD (r = 0.188, p = 0.0167). BMD at the neck of femur correlated with BMI (r = 0.391, p < 0.0001), age (r = -0.356, p < 0.0001), PTH (r = -0.156, p = 0.047) and serum 25OHD (r = 0.231, p = 0.0031). Stepwise multiple regression analysis showed that age, BMI and serum 25OHD contributed to the variation in BMD at lumbar spine. At the neck of femur, PTH was an additional contributor. We conclude that serum 25OHD makes a contribution to BMD a lumbar spine and neck of femur.

Adult↗
PubMed1998

Influence of risk factors on peripheral and cerebrovascular disease in men with coronary artery disease, low high-density lipoprotein cholesterol levels, and desirable low-density lipoprotein cholesterol levels. HIT Investigators. Department of Veterans Affairs HDL Intervention Trial.

BACKGROUND: The Veterans Administration-HDL Intervention Trial is an ongoing, 20-center, randomized, double-blind, placebo-controlled study aiming to assess the effect of gemfibrozil-improved low high-density lipoprotein cholesterol levels on cardiovascular morbidity and mortality rates. METHODS AND RESULTS: Eligible patients were men with low high-density lipoprotein cholesterol levels and demonstrable coronary heart disease. A total of 2531 patients (average age 63.5 years) were randomly assigned in this study, with a mean high-density lipoprotein cholesterol level of 0.83 mmol/L (32 mg/dL) and low-density lipoprotein cholesterol level of 2.87 mmol/L (111 mg/dL). Baseline data provided the opportunity to assess the interaction of several coronary heart disease risk factors and comorbid vascular diseases. Of these patients, 206 had diabetes mellitus (DM) alone, 1021 had hypertension (HTN) alone, 421 had both DM and HTN, and 883 had neither ("others"). Considering the influence of these risk factors on comorbidities independent of smoking status, patients with DM alone had a 2-fold increase in the prevalence of peripheral vascular disease and a 1.5-fold increase in congestive heart failure. Patients with HTN had a significant increase in the prevalence of cerebrovascular disease, stroke, and congestive heart failure. Patients with HTN and DM had a significant increase in all comorbidities. Smoking resulted in substantial increase of both peripheral vascular disease and cerebrovascular disease. Compared with nonsmoking patients with no DM or HTN, patients with DM and HTN and smoking had a 3-fold increase in the prevalence of peripheral vascular disease and a 3.5-fold increase in cerebrovascular disease (P < .001). CONCLUSIONS: We conclude that DM is a strong correlate of peripheral vascular disease, hypertension of cerebrovascular disease, and that there is a strong additive effect between DM, HTN, and smoking on both.

Aged↗
PubMed1998

Separation of omphalopagus twins: unique reconstruction using syngeneic cryopreserved tissue.

Omphalopagus twin girls were admitted for evaluation of possible separation and repair at age 7 days. Prenatal sonographic diagnosis occurred late in the third trimester and was followed by cesarean section delivery shortly thereafter. Results of extensive evaluation over the next 7 days including x-rays, computed tomography and ultrasound scan of the head and torso, and cardiac catheterization showed: the gastrointestinal tracts were separate and normal, the livers were joined but had separate biliary and vascular systems, and the hearts were separate with vastly different anatomy and function. One twin (twin A) had a normal heart with a small insignificant VSD. Twin B had a single ventricle, an incompetent A-V valve, stenotic pulmonic valve, ASD, PDA, and congenital heart block. Hemodynamic support of twin B was almost entirely from twin A. The vascular communications between the two consisted of a major connection between the internal mammary arteries and large arterial and venous connections traversing the joined livers. Because of continued deterioration of twin B, separation was undertaken at age 15 days. The separation included dividing the liver and the multiple large vascular connections. Two teams then reconstructed each twin separately. Twin B began showing signs of cardiac decompensation shortly after separation in spite of placement of a pacemaker, pulmonary artery banding, and ligation of the PDA. Cardiac function rapidly deteriorated and she died. Tissue from her chest wall was cryopreserved and placed in the tissue bank. Twin A underwent closure of her abdomen, and received a temporary bovine pericardial patch over the chest defect. She subsequently underwent placement of a graft of twin B's rib cage to bridge the bony chest defect and skin flap closure. She is presently taking a normal diet and thriving at home at age 18 months. The use of cryopreserved tissue from a syngeneic source provides a unique method of reconstruction in this situation.

Abdomen↗
PubMed1998

Expansion and division of conjoined twins.

Omphalopagus conjoined twins were born by cesarean section after their 24-year-old gravida 2, para 1 mother went into labor at 35 weeks' gestation. Initial studies included roentenograms, an upper gastrointestinal study, small bowel follow-through, and computerized tomography with intravenous contrast from neck through pelvis. Results of these studies showed that the twins had very little shared vasculature, but did share a pericardium and liver parenchyma. The infants were allowed to gain weight and grow. After 3 weeks, tissue expanders were placed subcutaneously and were rapidly expanded in 2 weeks. The infants were then separated. An Argon Beam Coagulator was used to aid the separation of the liver. The abdominal fascia was closed primarily on each infant, and the skin easily closed without tension. During the first 36 hours of the postoperative course, both infants required significant ventilatory support including inhaled nitric oxide. After this period, the ventilatory support decreased dramatically and rapidly. The infants were discharged 9 days after their surgical separation. Conjoined omphalopagus twins, the use of tissue expanders and the Argon Beam Coagulator, and the postoperative course are discussed.

Contrast Media↗
PubMed1998

The relationship between the female menopause and serum sialic acid, a known cardiovascular risk factor.

Serum total sialic acid (SA) has recently been reported as a cardiovascular risk factor. The risk of cardiovascular disease increases after the menopause in females. However, there are little data looking at the relationship between serum SA and the menopause. Overall 92 females were studied. The women were divided into five groups: the first three groups were age-matched pre-menopausal (n = 20), peri-menopausal (n = 10) and post-menopausal women (n = 20). In order to study serum SA changes with adult female age we also studied 14 young pre-menopausal women and 28 elderly women. There was no significance difference between the serum SA concentration in the age-matched pre-, peri- or post-menopausal women (62.7 +/- 10.4 mg/dl, 61.7 +/- 4.5 mg/dl, 62.9 +/- 7.0 mg/dl respectively). Furthermore, there was no significant difference between the serum SA in the "young" women (64.7 +/- 9.8 mg/dl) and that of the peri-, pre- or post-menopausal women. However, in the elderly women the serum SA was elevated (75.6 +/- 16.6 mg/dl) with P < 0.05 for each comparison group. In conclusion, serum SA does not seem to change at the time of the female menopause although in elderly women (average age 75.6 +/- 16.6 years) it increases. The reason for this increase is not known and may merit further research.

Adolescent↗
PubMed1998

Insulin-like growth factor-I and bone mineral density.

To assess the relationship between insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) 201 healthy postmenopausal women (age 41-68 years) within 10 years of menopause were studied. In all subjects, BMD at the lumbar spine and left hip were measured using dual-energy X-ray absorptiometry and blood samples were obtained. In all subjects, serum IGF-I and parathyroid hormone (PTH) were measured. In a subgroup of these subjects serum concentrations of IGF-binding protein-3 (IGFBP-3), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), and carboxyterminal propeptide of type I procollagen (PICP) were also measured. Serum IGF-I correlated significantly with age (r = -0.159, p = 0.0241), serum OC (r = 0.226, p = 0.0131), BALP (r = 0.259, p < 0.0001), and TRAP (r = 0.261, p < 0.0015), but not with PICP, PTH, or BMD at any site. Although there was a strong correlation between IGF-I and IGFBP-3 (r = 0.559, p < 0.0001), there was no correlation between IGFBP-3 and any of the markers of bone turnover (OC, BALP, TRAP, or PICP) nor with PTH or BMD at any site. We conclude that IGF-I and markers of bone turnover are related, but there is no relationship between IGF-I and BMD.

Absorptiometry, Photon↗
PubMed1998

Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type II collagen arthritis.

PURPOSE: To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-1ra) in rats with established type II collagen arthritis. METHODS: Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-1ra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-1ra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-1ra in CSEP or HA. RESULTS: Incorporation into HA led to slower release of IL-1ra into the bloodstream and maintained therapeutic blood levels of IL-1ra for a longer time compared to the IL-1ra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-1ra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-1ra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-1ra in HA resulted in 62% inhibition. IL-1ra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics. CONCLUSIONS: Administration of IL-1ra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.

Animals↗
PubMed1998

IGF-I increases forearm blood flow without increasing forearm glucose uptake.

Decreased insulin-mediated muscle glucose uptake is a characteristic feature of non-insulin-dependent diabetes mellitus and other insulin-resistant states. It has been suggested that an impairment in the ability of insulin to augment limb blood flow, resulting in diminished glucose delivery to muscle, may contribute to this abnormality. In this study, we used human insulin-like growth factor (IGF) I in conjunction with the forearm balance technique to determine whether forearm glucose uptake could be stimulated by increasing blood flow without directly stimulating the intrinsic ability of the muscle to extract glucose. IGF-I was infused intra-arterially in healthy controls at a rate of either 0.4 microg . kg-1 . min-1 (high IGF) or 0.04 microg . kg-1 . min-1 (low IGF) for 140 min. With high IGF, forearm blood flow increased approximately twofold (34 +/- 3 vs. 64 +/- 8 ml . min-1 . l forearm volume-1, P < 0.01), and arteriovenous glucose concentration difference (a-v difference) increased modestly (0.19 +/- 0.05 vs. 0.31 +/- 0.08 mM, P = 0.32), resulting in an increased forearm glucose uptake (6.4 +/- 1.7 vs. 21.7 +/- 7.4 micromol . min-1 . l forearm volume-1, P = 0.09 vs. basal). With low IGF, forearm blood flow increased by 59% (29 +/- 4 vs. 46 +/- 9 ml . min-1 . l forearm volume-1, P < 0.05) and was associated with a proportional decrease in the a-v difference (0. 29 +/- 0.04 vs. 0.18 +/- 0.05 mM, P < 0.05). Forearm glucose uptake therefore was not significantly different from basal values (7.6 +/- 0.6 vs. 6.9 +/- 1.8 micromol . min-1 . kg-1). These data demonstrate that increasing blood flow without increasing the intrinsic ability of the muscle to extract glucose does not increase forearm muscle glucose uptake.

Adult↗
PubMed1998

Spontaneous cleft palate in a newborn gorilla (Gorilla gorilla gorilla).

OBJECTIVE: We report the first case of cleft palate in a newborn male gorilla (Gorilla gorilla gorilla). CASE HISTORY AND RESULTS: The full-term infant was born to clinically healthy, wild-caught parents and survived 5 days. Autopsy disclosed a unilateral cleft palate, moderate scalp hemorrhage (birth versus postnatal trauma), cerebral edema, and a sterile fibrin vegetation in the heart. The palate was also shorter and narrower than expected, and the biorbital breadth was reduced; otherwise, growth and development appeared normal. Standard cranial and intraoral radiographs and three-dimensional reconstructions of computerized tomographic (CT) scans provided thorough and noninvasive methods of studying the craniofacial complex and extracranial skeleton. By this technique, major findings were: intact premaxilla, interpremaxillary, and premaxillary/maxillary sutures; intramaxillary cleft with ipsilateral choanal atresia; mildly asymmetric inferior turbinates; and normal nasal septum and vomer. CONCLUSIONS: Except for choanal atresia, cleft palate was not associated with other major craniofacial or extracranial anomalies in this case. Choanal atresia has been observed at times with cleft palate, but to our knowledge, the association has not been reported in nonhuman primates. Cleft palate, with or without cleft lip, has been recognized in a variety of nonhuman primates, including the lemur, marmoset, tamarin, squirrel monkey, and macaque. Some occurrences are spontaneous, while others are syndromic and/or arise from genetic or teratogenic influences. Each mode of presentation is poorly understood in nonhuman primates, but in this case, the absence of relevant environmental or parental history suggests that the occurrence was spontaneous. Anatomic studies of nonhuman primates are particularly valuable when they involve endangered species and will hopefully increase our understanding of the pathogenesis and etiology of congenital disorders, as well as other relationships between nonhuman primates and humans.

Animals↗
PubMed1998

Measurement of exercise dependence in bodybuilders.

OBJECTIVE: The purpose of this study was to explore exercise dependence in bodybuilders, and undertake preliminary validation of a measurement instrument. EXPERIMENTAL DESIGN: A comparative analysis of self-report indices between groups. PARTICIPANTS: Forty-seven bodybuilders, 31 individuals who weight trained for general fitness purposes and 24 weightlifters participated in the study. MEASURES: Each subject completed the following: demographic information, bodybuilding-specific versions of the social identity and exclusivity scales of the Athletic Identity Measurement Scale, the physical strength and body attractiveness subscales of the Physical Self-Perception Profile, a short form of the Marlowe-Crowne Social Desirability Scale, and a 9-item Bodybuilding Dependence Scale. RESULTS: Factor analysis on the BDS revealed 3 subscales (social dependency, training dependency and mastery) which accounted for 68.4% of the variance. Internal consistency was satisfactory for each subscale (Chronbach's alpha = 0.76, 0.75 and 0.78 respectively). The BDS social dependency and PSPP body attractiveness scores of the bodybuilders were higher than those of the weightlifters, whose scores were higher than those of the fitness trainers. The bodybuilders scored higher on both AIMS subscales than the other groups. The bodybuilders and weightlifters scored higher on PSPP physical strength than the fitness trainers. BDS social dependency correlated with both AIMS and both PSPP subscales, and BDS training dependency correlated with AIMS exclusivity. All three BDS subscales correlated with training frequency. Discriminant analysis found the combination of AIMS social identity, BDS social dependency and years training experience enabled correct classification of 92% of the respondents. CONCLUSIONS: These results support the construct and concurrent validity of the BDS social dependency subscale, but do not wholly support the validity of the other two subscales.

Adult↗
PubMed1998

An investigation of the interrelationship between manipulative therapy-induced hypoalgesia and sympathoexcitation.

OBJECTIVE: To investigate a proposed model in which manipulative therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect by activating a descending pain inhibitory system. The a priori hypothesis tested was that manipulative therapy produces mechanical hypoalgesia and sympathoexcitation beyond that produced by placebo or control. Furthermore, these effects would be correlated, thus supporting the proposed model. DESIGN: A randomized, double-blind, placebo-controlled, repeated-measures study of the initial effect of treatment. SETTING: Clinical neurophysiology laboratory. SUBJECTS: Twenty-four subjects (13 women and 11 men; mean age, 49 yr) with chronic lateral epicondylalgia (average duration, 6.2 months). INTERVENTION: Cervical spine lateral glide oscillatory manipulation, placebo and control. OUTCOME MEASURES: Pressure pain threshold, thermal pain threshold, pain-free grip strength test, upper limb tension test 2b, skin conductance, pileous and glabrous skin temperature and blood flux. RESULTS: Treatment produced hypoalgesic and sympathoexcitatory changes significantly greater than those of placebo and control (p < .03). Confirmatory factor-analysis modeling, which was performed on the pain-related measures and the indicators of sympathetic nervous system function, demonstrated a significant correlation (r = .82) between the latencies of manipulation-induced hypoalgesia and sympathoexcitation. The Lagrange Multiplier test and Wald test indicated that the two latent factors parsimoniously and appropriately represented their observed variables. CONCLUSION: Manual therapy produces a treatment-specific initial hypoalgesic and sympathoexcitatory effect beyond that of placebo or control. The strong correlation between hypoalgesic and sympathoexcitatory effects suggests that a central control mechanism might be activated by manipulative therapy.

Adult↗
PubMed1997

Rapid differentiation of bovine and human tubercle bacilli based on a characteristic mutation in the bovine pyrazinamidase gene.

Bovine tuberculosis (TB) caused by Mycobacterium bovis is an important veterinary disease that can also afflict humans. Although M. bovis shares an almost identical genome with M. tuberculosis, subtle differences in host specificity and several biochemical parameters can be used to distinguish the two closely related species. The current method for distinguishing M. bovis from M. tuberculosis relies on tedious testing of biochemical parameters, including natural resistance to pyrazinamide and defective pyrazinamidase (PZase) activity of M. bovis strains. In this study, we report the development of a rapid PCR-single-strand conformation polymorphism (SSCP) assay to differentiate M. bovis from M. tuberculosis strains, based on the detection of a single characteristic point mutation in the PZase gene (pncA) of M. bovis. Eighty-seven of 89 M. bovis strains could be distinguished from M. tuberculosis strains. Surprisingly, two animal isolates which were initially identified as M. bovis were shown to be M. africanum because they had a wild-type pncA sequence with positive PZase. These two M. africanum strains contain multiple (three and six) copies of insertion sequence IS6110, a feature they have in common with M. tuberculosis. The implication of this finding for the taxonomy of M. tuberculosis complex is discussed in relation to host preference and epidemiology. The development of a rapid PCR-SSCP test for distinguishing M. bovis from M. tuberculosis will be useful for monitoring the spread of bovine TB to humans in areas where bovine TB is endemic and for directing the treatment of human TB caused by M. bovis.

Amidohydrolases↗
PubMed1997

Carotid atherosclerosis in men with low levels of HDL cholesterol.

BACKGROUND AND PURPOSE: A low HDL cholesterol (HDL-C) frequently occurs in conjunction with a desirable LDL cholesterol (LDL-C) and is a risk factor for coronary heart disease (CHD). Additionally, the presence of carotid atherosclerosis is a strong and independent predictor of morbidity and mortality in patients with CHD. This article describes the prevalence and correlates of sonographically detected carotid atherosclerosis in men with low levels of HDL-C and CHD but without elevated levels of LDL-C or total cholesterol. METHODS: High-resolution B-mode ultrasonography was used to quantify intima-media wall thickness (IMT) in the common and internal carotid arteries and at the carotid artery bifurcation in 202 randomly selected male veterans with CHD and low levels of HDL-C who are participating in the VA HDL Intervention Trial. Ultrasonographic measurement of carotid artery wall stiffness was determined in a subset of 94 of these individuals. RESULTS: The mean maximum and single greatest carotid artery IMT measurements were 1.41 and 2.58 mm, respectively. The prevalence of ultrasound-detected carotid atherosclerosis as defined by a mean maximum IMT > or = 1.3 mm was 58.9% and by single maximum IMT > or = 1.5 mm was 87.1%. IMT was associated with increased age, lower extremity arterial disease, systolic blood pressure, and ultrasonographically measured carotid artery stiffness. CONCLUSIONS: Men with low levels of HDL-C and CHD but without elevated LDL-C or total cholesterol have a very high prevalence of ultrasound-detected carotid artery atherosclerosis.

Aged↗
PubMed1996

Stabilization of granulocyte colony-stimulating factor and structurally analogous growth factors by anionic phospholipids.

Recombinant granulocyte colony-stimulating factor (rhG-CSF) interacts with liposomes composed of the anionic phospholipid dioleoylphosphatidylglycerol (DOPG), and this interaction enhances the stability of the protein [Collins, D., & Cha, Y. (1994) Biochemistry 33, 4521-4526]. In the present studies, we have examined the interaction of rhG-CSF with phospholipids other than DOPG. Fluorescence spectroscopy of rhG-CSF with a variety of lipid vesicles demonstrated that rhG-CSF inserts into bilayers of anionic, but not zwitterionic, phospholipids. Isothermal titration calorimetry of the interaction between DMPG and rhG-CSF indicates that the binding is saturable and involves 10 lipids/rhG-CSF. Studies of phosphatidylglycerols with varying alkyl chain lengths determined that the stabilization of rhG-CSF by anionic phospholipids required a certain alkyl chain length; no stabilization was observed with lipids of shorter chain length. Also investigated was the stabilization of other growth factors, which are structurally similar to rhG-CSF, by anionic phospholipids. These proteins include recombinant porcine somatotropin (rpSt), recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), recombinant human interleukin 4 (rhIL-4), and recombinant human interleukin 2 (rhIL-2). The helical secondary structure of the proteins was recoverable after heating and cooling in the presence of anionic phospholipids as observed by circular dichroism; the presence of zwitterionic lipids did not induce this effect. Results of these investigations concluded that a group of structurally similar proteins interact preferentially with anionic phospholipids and that the complexation of the growth factors with vesicles composed of anionic phospholipids improves the stability of the proteins under conditions where they normally denature.

Calorimetry, Differential Scanning↗
PubMed1996

The Veterans Affairs High-Density Lipoprotein Intervention Trial: baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group.

This report describes the baseline characteristics of the 2,531 patients with coronary artery disease enrolled in the Veterans Affairs Cooperative Studies Program High Density Lipoprotein Intervention Trial. The population is characterized by a large percentage of elderly patients, diabetic patients, and patients with the clinical characteristics of the insulin-resistance syndrome.

Adult↗
PubMed1996

Fate of cationic liposomes and their complex with oligonucleotide in vivo.

The present studies describe the biodistribution of cationic liposomes and cationic liposome/oligonucleotide complex following intravenous injection into mice via the tail vein. (111)In-diethylenetriaminepentaacetic acid stearylamide ((111)In-DTPA-SA) was used as a lipid-phase radiolabel. Inclusion of up to 5 mol% DTPA-SA in liposomes composed of 3beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol) and dioleoylphosphatidylethanolamine (DOPE) did not influence liposome formation or size, nor the binding/uptake or fusion of the cationic liposomes with CHO cells in vitro. Moreover, nuclear delivery of oligonucleotide to CHO cells was unaffected by the probe. The biodistribution of liposomes with increasing concentration of DC-Chol (1:4-4:1, DC-Chol/DOPE, mol/mol) at 24 h post-injection revealed no dependence on lipid composition. Uptake was primarily by liver, and accumulation in spleen and skin was also observed. Comparatively little accumulation occurred in lung. Clearance of injected liposomes by liver was very rapid (approximately 84.5% of the injected dose by 7.5 h post-injection). Liposome uptake by liver and spleen were equally efficient in the dose range of 3.33 to 33.33 mg/kg body weight, yet possible saturation of liver uptake at a dose of 66.80 mg/kg may have allowed for increased spleen accumulation. Preincubation of cationic liposomes with phosphorothioate oligonucleotide induced a dramatic yet transient accumulation of the lipid in lung which gradually redistributed to liver. Similar results were observed when monitoring iodinated oligonucleotide in the complex. Immuno-histochemical studies revealed large aggregates of oligonucleotide within pulmonary capillaries at 15 min post-injection, suggesting the early accumulation in lung was due to embolism. Immuno-histochemical studies further revealed labeled oligonucleotide to be localized primarily to Kupffer cells at 24 h post-injection. Immuno-electron microscopy revealed localization of oligonucleotide primarily to the lumen of pulmonary capillaries at 15 min post-injection. Immuno-electron microscopy revealed localization of oligonucleotide primarily to the lumen of pulmonary capillaries at 15 min post-injection, and to phagocytic vacuoles of Kupffer cells at 24 h post-injection. By these methods, nuclear delivery of oligonucleotide in vivo was not observed. Increasing concentration of mouse serum inhibited cellular binding/uptake of cationic liposomes in vitro, without or with complexed oligonucleotide. We therefore postulate that interaction with plasma components, including opsonin(s), inhibits cellular uptake of the injected liposomes as well as the liposome/oligonucleotide complex, and mediates rapid uptake by Kupffer cells of the liver. These results are relevant to the design of cationic liposomes for efficient delivery of nucleic acid in vivo.

Animals↗