Biomedical subjects

R L Hamilton

Publications and source records attributed to R L Hamilton.

At least 73 records · Page 4Linked to original sources

PubMed1997

Isolation of subpopulations of high density lipoproteins: three particle species containing apoE and two species devoid of apoE that have affinity for heparin.

We have isolated and partially characterized five populations of lipoproteins from the pool of immunoisolated apoA-I-containing lipoproteins obtained from normal human plasma. The first three populations, each containing apoA-I and apoE, were isolated completely by sequential, selected affinity immunosorption against apoA-I and apoE. The lipoproteins isolated by this strategy fall into three morphologic groups; there are discs (LP-AI-E(1)), small spherical lipoproteins (LP-AI-E(2)), and large spherical lipoproteins (LP-AI-E(3)). The LP-AI-E(2) species was sufficiently abundant for detailed characterization. They have slightly larger diameters, and contain more lipid than the bulk of apoA-I-containing lipoproteins and they contain apoA-II:E heterodimers and apoE homodimers. Core lipids are enriched in triglyceride relative to cholesteryl esters. These lipoproteins compete with LDL equally, on a protein mass basis, for binding to human fibroblasts. After removal of apoE-containing lipoproteins from the pool of apoA-I-containing lipoproteins, we discovered two additional subpopulations of lipoproteins that bind to heparin. These lipoproteins, devoid of apoE, occur as populations of small, (LP-AI-HB(1)), and large, spherical lipoproteins, (LP-AI-HB(2). The heparin-binding lipoproteins were separated by gel permeation chromatography. The LP-AI-HB(1) population was of sufficient quantity for detailed study. These lipoproteins also had larger diameters than the bulk of HDL but their core lipids were enriched in cholesteryl esters rather than triglycerides. Three proteins associated with these lipoproteins were found to bind to heparin-Sepharose in the absence of lipid. The approximate molecular weights of these proteins are 40, 70, and 90 kDa. The 70 kDa molecule was found to be the SP 40,40 protein (apoJ).

Apolipoprotein A-I↗

PubMed1997

Basic fibroblast growth factor expression as a predictor of prognosis in pediatric high-grade gliomas.

Clinical and histopathological factors fail to adequately predict outcomes in children with high-grade gliomas, indicating a need to identify relevant biological markers of tumor behavior to guide therapeutic decision-making. Basic fibroblast growth factor (bFGF) is a mitogenic and angiogenic factor that has been observed to be overexpressed in a significant percentage of malignant gliomas, although the prognostic significance of this expression is unknown. To address this issue, the expression status of bFGF was examined immunohistochemically in a series of 27 archival pediatric malignant non-brainstem gliomas treated consecutively at our institution between 1975 and 1992. Tumors were categorized based on expression levels, and the association between expression status and outcome was examined. Sixteen cases showed high levels of expression of bFGF, and 11 showed low levels. There was no correlation between expression status and either tumor histology, patient age, or tumor location. However, there was a significant difference in outcome between patients with high levels of bFGF immunoreactivity and those with low expression. Median progression-free survival was >66 months in the low bFGF group as compared to 6 months in the high bFGF group (P = 0.006). Median overall survival was >66 months in the low bFGF group as compared to 18 months in the high bFGF group (P = 0.03). Tumor bFGF expression seems to be strongly associated with outcome in children with high-grade gliomas and, consequently, may serve as a biological correlate of patient prognosis in conjunction with other prognostic variables.

Adolescent↗

PubMed1996

Unusual case of inflammatory spinal epidural mass (Castleman syndrome).

Castleman syndrome (giant lymph node hyperplasia) is a rare, heterogeneous lymphoproliferative disorder of unknown etiology and pathogenesis. Most cases occur as mediastinal masses, although extrathoracic involvement including nodal and extranodal locations have been reported. The localized variants (solitary lesions) respond well to surgical excision. We report a 10-year-old boy who presented with headache, intermittent fever, and progressive weakness of his legs. MRI imaging showed an enhancing epidural mass with impingement on the spinal cord at the C6-T2 level. Other laboratory abnormalities included anemia, hypergammaglobulinemia, increased erythrocyte sedimentation rate, and cerebrospinal fluid pleocytosis with slightly increased cerebrospinal protein. The mass was partially resected and the histopathology showed lymphoplasmocytic infiltration compatible with Castleman syndrome. There was no evidence of malignancy. Castleman syndrome is the most likely diagnosis in the presence of the associated systemic findings, although the epidural site for lymphoplasmocytic inflammation is atypical.

Castleman Disease↗

PubMed1996

A meningeal cyst of the thoracic spine presenting as prolonged paresis after ankle injury: case report.

A case of a thoracic meningeal cyst causing right lower extremity weakness in a fifteen-year-old girl is presented. The diagnosis was delayed due to a history of ankle injury which was initially used to explain her symptoms. The authors explain the difficulty in diagnosing intraspinal meningeal cysts and stress the importance of surgical excision before spinal cord injury progresses.

Adolescent↗

PubMed1996

Effects of hypothermia on traumatic brain injury in immature rats.

Hypothermia is beneficial in adult models of traumatic brain injury (TBI), but it has not been evaluated in an immature animal model. We hypothesized that brief hypothermia applied after TBI would reduce cerebral edema and lesion volume in immature rats. Male Wistar rats (3-4 weeks of age, 90-140 g) were anesthetized, intubated, mechanically ventilated, and subjected to TBI by weight drop onto the exposed right parietal cortex. Hypothermic rats were then cooled to a brain temperature of 32.0 +/- 0.5 degrees C for 4 h, and control rats were maintained at a brain temperature of 37.0 +/- 0.5 degrees C. Cerebral edema (wet - dry weight method) was assessed at 5 days. At 4 h, a reduction of percent brain water in the traumatized hemisphere was observed in hypothermic versus normothermic rats (81.75 +/- 0.60 vs. 82.53 +/- 0.67%; p<0.05), but by 24 h posttrauma, the groups were similar (p = 0.82). Total lesion volume (47.2 +/- 8.5 vs. 44.4 +/- 10.0 mm3; p = 0.51) and necrotic volume (20.2 +/- 6.3 vs. 20.0 +/- 7.9 mm3; p = 0.95) were similar in the hypothermic and normothermic groups. We conclude that in this model, a transient (4-h) application of moderate (32 degrees C) hypothermia reduces the cerebral edema characteristically seen in immature rats at 4 h, but this reduction is not sustained at 24 h. Attenuating or delaying the development of cerebral edema could have important therapeutic relevance after TBI. Transient hypothermia, however, did not reduce lesion volume at 5 days posttrauma.

Aging↗

PubMed1996

Case of the month. May 1996--hydrocephalus in a 9 month old infant.

A 9 month old infant presented with hydrocephalus. MRI studies revealed a large cystic space with a nodule that was bright on T-1 weighted images and dark on T-2 weighted images. It was bright with contrast enhancement. The surgical specimen was noted to be dark black. Microscopic examination revealed a benign papillary tumor consistent with a choroid plexus papilloma which was heavily pigmented with melanin. Immunohisto-chemical stains were consistent with a choroid plexus papilloma, but they also showed many epithelial cells to be positive for HMB-45. Ultrastructural studies demonstrated melanosomes and pre-melanosomes in cells with well-delineated basal lamina. This is the first case to demonstrate melanosomes in a benign choroid plexus papilloma. Previously reported cases of pigmented lesions of the choroid plexus either contained neuromelanin in the benign examples or melanosomes in two cases of choroid plexus carcinomas.

Choroid Plexus Neoplasms↗

PubMed1996

A model of diffuse traumatic brain injury in the immature rat.

Diffuse cerebral swelling after severe traumatic brain injury (TBI) develops more commonly in children than adults; however, models of diffuse brain injury in immature animals are lacking. The authors developed a new model of diffuse severe TBI in immature rats by modifying a recently described closed head injury model for adult rats. A total of 105 Sprague-Dawley immature rats (17 days old; average weight 38.5 +/- 5.46 g) were subjected to head impact using variable weights (0 g (sham), 75 g, 100 g, or 125 g) delivered from a height of 2 m onto a metal disk cemented to the intact cranium. Mortality, physiological and neurological parameters (from early reflex recovery to escape), and early histopathological changes were assessed. During the acute period after severe injury (SI) (100 g delivered from a height of 2 m; 50 rats), apnea was frequently observed and the mortality rate was 38%. Neurological recovery was complete in the sham-injured animals (11 rats) by 4.1 +/- 0.23 minutes (mean +/- standard error of the mean), but was delayed in both moderately injured (MI) (75 g/2 m; 11 rats) (14.97 +/- 3.99 minutes) and SI (20.57 +/- 1.31 minutes (p < 0.05)) rats. In the first 24 hours, the sham-injured animals were more active than the injured ones as reflected by a greater net weight gain: 2.9 +/- 1.0 g, 1.2 +/- 1.6 g, and -0.6 +/- 2.1 g in sham-injured, MI, and SI animals, respectively. Immediately after injury, transient hypertension (lasting < 15 seconds) was followed by hypotension (lasting < 3 minutes) and loss of temperature regulation. Both injuries also induced apnea (0.75 +/- 0.7 minutes and 1.27 +/- 0.53 minutes in MI and SI groups, respectively), which either resolved or deteriorated to death. Intubation and assisted ventilation in animals with SI for 9.57 +/- 3.27 minutes in the peritrauma period eliminated mortality (p < 0.05, intubated vs. nonintubated). Histologically, after SI, there was diffuse edema throughout the corpus callosum below the region of injury and in the thalami. Other injuries included neuronal death in the deep nuclei, bilateral disruption of CA3, diffuse subarachnoid hemorrhage, and, in some, ventriculomegaly. Following a diffuse TBI in immature rats, SI produced a mortality rate, neurological deficit, and histological changes similar to those previously reported for an injury resulting from a 450-g weight dropped from 2 m in adult rats. A graded insult was achieved by maintaining the height of the weight drop but varying the weights. Weight loss, acute physiological instability, and acute neurological deficits were also indicative of an SI. Mortality was eliminated when ventilatory support was used during the peritrauma period. This model should be useful in studying the response of the immature rat to diffuse severe TBI.

Animals↗

PubMed1996

A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice.

Apolipoprotein (apo) B, the principal structural component necessary for the synthesis and secretion of triglyceride-rich lipoproteins by the intestine and liver, is highly expressed in the yolk sac visceral endoderm of mammals, although its function in this tissue has been hitherto unclear. Disruption of the apoB gene in mice results in embryonic lethality (approximately 9.5 - 10.5 d). Here we demonstrate that apoB is normally expressed at early time points in embryonic development in yolk sac visceral endodermal cells, and that this expression is associated with the synthesis and secretion of apoB-containing lipoproteins. The lack of apoB in the visceral endoderm resulted in an accumulation of intracellular lipid droplets, an absence of lipoproteins from the secretory pathway, and reduced concentrations of cholesterol and alpha-tocopherol in tissues of apoB-/- embryos. Visceral endoderm of apoB+/- embryos exhibited an intermediate phenotype. Our results suggest that apoB plays an essential role in the transport of lipid nutrients to the developing mouse embryo via the yolk sac-mediated synthesis and secretion of apoB-containing lipoproteins.

Animals↗

PubMed1995

Association of surfactant protein C with isolated alveolar type II cells.

Surfactant protein C (SP-C) is a small hydrophobic protein that is synthesized and secreted by alveolar type II cells. The mechanism of clearance of SP-C from the alveolar airspace is not well understood, although previous studies demonstrated that recombinant SP-C instilled into the lungs of spontaneously breathing anaesthetized rats was taken up by type II cells and incorporated into lamellar bodies. The current investigation was undertaken to characterize the interaction of a complex of SP-C and surfactant-like lipids with freshly isolated rat alveolar type II cells under conditions in which the extracellular milieu can be regulated. SP-C was isolated from alveolar proteinosis lavage fluid and radiolabeled with 125I-Bolton-Hunter reagent. The radiolabeled protein retained its ability to facilitate adsorption of phospholipids to an air/liquid interface. Labeled human SP-C associated with isolated type II cells in a concentration-dependent manner that was also dependent upon temperature and time. The association of labeled SP-C with isolated type II cells did not saturate up to 150 micrograms/ml. SP-A significantly enhanced the association of SP-C with isolated type II cells. Under the experimental conditions tested, SP-C was not degraded to TCA-soluble products. These results are consistent with the hypothesis that association or uptake of SP-C by type II cells may be enhanced by SP-A and that like SP-A, SP-C is recycled by type II cells.

Animals↗

PubMed1995

A genetic model for absent chylomicron formation: mice producing apolipoprotein B in the liver, but not in the intestine.

The formation of chylomicrons by the intestine is important for the absorption of dietary fats and fat-soluble vitamins (e.g., retinol, alpha-tocopherol). Apo B plays an essential structural role in the formation of chylomicrons in the intestine as well as the VLDL in the liver. We have developed genetically modified mice that express apo B in the liver but not in the intestine. By electron microscopy, the enterocytes of these mice lacked nascent chylomicrons in the endoplasmic reticulum and Golgi apparatus. Because these mice could not form chylomicrons, the intestinal villus enterocytes were massively engorged with fat, which was contained in cytosolic lipid droplets. These mice absorbed D-xylose normally, but there was virtually no absorption of retinol palmitate or cholesterol. The levels of alpha-tocopherol in the plasma were extremely low. Of note, the absence of chylomicron synthesis in the intestine did not appear to have a significant effect on the plasma levels of the apo B-containing lipoproteins produced by the liver. The mice lacking intestinal apo B expression represent the first genetic model of defective absorption of fats and fat-soluble vitamins and provide a useful animal model for studying nutrition and lipoprotein metabolism.

Animals↗

PubMed1995

Neuropathology of propionic acidemia: a report of two patients with basal ganglia lesions.

Propionic acidemia is a rare genetic disorder of amino acid metabolism caused by deficient activity of propionyl coenzyme A carboxylase. Neuropathologic changes previously reported in infants have been white-matter vacuolization or spongiosis. In children who survive beyond infancy, abnormalities have been found primarily in the basal ganglia. We report neuropathologic findings in two patients with propionic acidemia diagnosed in infancy who survived 35 months and 9 years, respectively. Examination of the brain of the 35-month-old boy showed vascular and parenchymal mineralization, focal pallor and spongy change, and foci of acute neuronal injury. These changes were similar to those previously described. The 9-year-old girl was in good metabolic control when she died, and presented a neuropathologic picture not previously described. She was found at autopsy to have acute hemorrhagic lesions in the caudate, putamen, and globus pallidus bilaterally and in the left ventral thalamus. There was focal neuronal loss, but no acute hypoxic/ischemic neuronal injury. Vascular proliferation and swollen endothelial cells were seen in the basal ganglia, thalamus, and substantia nigra, but not in other regions of the brain. Electron microscopy showed swelling of endothelial cells with viable adjacent brain parenchyma. The endothelial changes suggest a breakdown of the blood-brain barrier.

Basal Ganglia Diseases↗

PubMed1995

Cell surface "blanket" of apolipoprotein E on rat adrenocortical cells.

Apolipoprotein (apo) E is expressed at high levels by adrenocortical cells. In the present study, an affinity-purified antibody to rat apoE was used in combination with immunogold visualization at both the light and electron microscopic levels to determine the cellular and subcellular distribution of apoE within the rat adrenal cortex. At the light microscopic level, apoE was found primarily in z. fasciculata and z. reticularis with little or none detected in z. glomerulosa and medulla. Within the z. fasciculata and z. reticularis, apoE was present in the cytoplasm of all parenchymal cells. ApoE also was found on the cell surface both on the sinusoidal front and in regions well removed from the subendothelial space. Electron microscopic examination of the z. fasciculata showed that apoE on the sinusoidal front was on the parenchymal cell surface but not the endothelial cell. Cell surface apoE was prominent on microvilli as well as non-microvillar regions of plasma membrane in the subendothelial space. ApoE was also associated with the cell surface in intercellular spaces continuous with but well removed from the subendothelial space. These findings at the light and electron microscopic levels suggest that the z. fasciculata cell is encircled or covered with apoE on all faces of the cell. These results are consistent with the idea that this cell surface "blanket" of apoE participates in the uptake of lipoprotein cholesterol by either the endocytic or selective uptake pathways.

Adrenal Glands↗

PubMed1995

ACAT inhibitors decrease secretion of cholesteryl esters and apolipoprotein B by perfused livers of African green monkeys.

To test the hypothesis that newly synthesized cholesteryl esters are required for hepatic lipoprotein assembly and secretion, isolated livers of African green monkeys were perfused with medium containing an ACAT inhibitor. Three ACAT inhibitors with different structural and chemical properties were used: CI-976 (Parke-Davis), CP-113818 (Pfizer), or PD-138142-15 (Parke-Davis). Each compound produced variable effects on secretion of lipids and apolipoproteins. A significant decrease in the secretion rates of cholesteryl ester and apoB was common to all three inhibitors, indicating that fewer lipoprotein particles were secreted during ACAT inhibition. Triacylglycerol secretion was decreased in the presence of CP-113818 and PD-138142-15 but no decrease in triacylglycerol secretion was observed with CI-976. Particles secreted in the presence of CI-976 were enriched in triacylglycerol relative to apoB. Effects on secretion of other apolipoproteins (apoA-I, apoA-II, and apoE) were variable. When all data were combined, the percent inhibition of cholesteryl ester secretion and apoB secretion in the presence of ACAT inhibitors was positively correlated (r = 0.84), whereas a similar relationship was not observed between triacylglycerol and apoB. While the results demonstrate some lack of specificity for these ACAT inhibitors, the complimentary results using the three different ACAT inhibitors suggest that secretion of cholesteryl ester and apoB are coordinately regulated. The data suggest that newly synthesized cholesteryl esters may participate in and promote the assembly and secretion of hepatic apoB-containing lipoproteins. The availability of triacylglycerol during lipoprotein assembly, while also important, would appear to serve a role separate from that of cholesteryl ester.

Anilides↗

PubMed1994

Conformational differences in human apolipoprotein B-100 among subspecies of low density lipoproteins (LDL). Association of altered proteolytic accessibility with decreased receptor binding of LDL subspecies from hypertriglyceridemic subjects.

We asked at what point in the metabolic cascade of very low density lipoproteins (VLDL) to low density lipoproteins (LDL) the accessibility of proteolytic cleavage sites in B-100 changes, and we evaluated the effect of hypertriglyceridemia on the proteolytic accessibility, secondary structure, and receptor-binding affinity of B-100 in LDL subspecies of varying density. Limited proteolysis with Staphylococcus aureus V8 protease and cathepsin D identified the density (about 1.033 g/ml) between two LDL subspecies, designated LDL-1 and -2, as the transition point during VLDL metabolism of both normolipidemic (N-) and hypertriglyceridemic (HTG-) subjects at which accessibility to protease attack changed in three peptide regions of B-100. Hypertriglyceridemia greatly altered proteolytic accessibility of B-100 in the denser LDL subspecies. Specifically, B-100 in HTG-LDL exposed more cleavage sites than in N-LDL, including two novel sites, approximately 120 and approximately 130 kDa from the NH2 terminus in the small and dense subspecies (designated LDL-4, -4.5 or -5, d = 1.048-1.062 g/ml). Analysis of circular dichroic spectra indicated no difference in helical content between B-100 in N- and HTG-LDL but showed a greater content of beta-structure in HTG-LDL. Binding affinity for the LDL receptor of human fibroblasts decreased markedly with increasing density among HTG-LDL subspecies (by approximately 50% for LDL-4.5 or -5). We conclude that the changes in proteolytic accessibility observed between LDL-1 and -2 and in LDL-4, -4.5, or -5 indicate significant differences in local conformation of B-100 at specific peptide regions. The association of exposure of more cleavage sites, especially novel sites in the NH2-terminal regions, with greatly decreased receptor-binding affinity in LDL-4.5 or -5 suggests that altered local conformation in B-100 apart from the putative receptor-binding domain might affect interaction with the receptor.

Apolipoprotein B-100↗

PubMed1994

Muscle pathology and clinical measures of disability in children with cerebral palsy.

We performed a histologic and morphometric study of spastic muscle from 10 children with diplegic cerebral palsy, comparing muscle structure with the gait parameters of energy expenditure index and dynamic electromyography. Variations in fiber area within and between fiber types were increased significantly in children with cerebral palsy. In each of the control subjects, the combined coefficient of variation for type-1 and type-2 fiber area was less than 25% and the average was 17%; in the subjects with cerebral palsy, the combined coefficient of variation was more than 25% and the average was 36% (p < or = 0.004). The average difference between the mean area of type-1 and type-2 fibers was 26.7 +/- 18.9% for subjects with cerebral palsy and 4.2 +/- 2.4% for control subjects (p < or = 0.004). There was a 67% predominance of one fiber type in the subjects with cerebral palsy compared with a 55% predominance in the control subjects (p < or = 0.03). The difference between the total area of type-1 and type-2 fibers was 57% in the subjects with cerebral palsy and 17% in the control subjects (p < or = 0.002). There was a significant correlation between the combined coefficient of variation of fiber area and the energy expenditure index (r = 0.77, p < or = 0.03). The difference between the mean area of type-1 and type-2 fibers correlated with prolongation of electromyographic activity (r = 0.69, p < or = 0.05). No abnormalities in fiber ultrastructure were found in the subjects with cerebral palsy. Children with cerebral palsy had abnormal variation in the size of muscle fibers and altered distribution of fiber types. The values for variation in fiber area correlated with the energy expenditure index and with prolongation of electromyographic activity during walking.

Adolescent↗

PubMed1994

Complete absence of the cerebellum: a report of two cases.

Complete absence of the cerebellum is an extremely rare malformation. Most previous cases have had some remnant of cerebellar cortex, however small. We report two infants with complete absence of the cerebellum. One infant had hydrocephalus and numerous other malformations. The other infant had micrencephaly, which has not previously been reported in association with an absent cerebellum.

Abnormalities, Multiple↗

PubMed1994

Triglyceride-rich lipoproteins isolated by selected-affinity anti-apolipoprotein B immunosorption from human atherosclerotic plaque.

We isolated and characterized immunoreactive apolipoprotein B (apoB)-containing lipoproteins from human atherosclerotic plaque and plasma to determine whether very-low-density lipoprotein (VLDL) can enter and become incorporated into the atherosclerotic lesion and how plaque apoB-containing lipoproteins differ from apoB-containing lipoproteins isolated from plasma. Atherosclerotic plaques were obtained during aortic surgery and processed immediately. Lipoproteins were extracted from minced plaque in a buffered saline solution (extract A). In selected cases a second extraction was done after plaque was incubated with collagenase (extract B). Lipoproteins were then isolated from the extracts by anti-apoB immunosorption and separated into VLDL + intermediate-density lipoprotein (IDL) (d < 1.019 g/mL) and low-density lipoprotein (LDL) (1.019 < d < 1.070 g/mL) fractions by ultracentrifugation. The VLDL + IDL fractions from plaque contained more than one third of the total apoB-associated lipoprotein cholesterol in both extracts A and B. The lipid composition of VLDL + IDL in both extracts was related to that of plasma VLDL + IDL. By electron microscopy mean particle diameters of VLDL + IDL from extracts A and B were 9% and 23%, respectively, greater than VLDL + IDL diameters from plasma. Mean diameters of LDL from extracts A and B were 11% and 31% greater than LDL diameters from plasma. The apoE-apoB ratio of extract A VLDL + IDL was nearly twice that of plasma VLDL + IDL and severalfold higher than that of extract A LDL. Immunoblots of both VLDL + IDL and LDL from extract A demonstrated minimal fragmentation of apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1993

Low density lipoprotein- and high density lipoprotein-mediated signal transduction and exocytosis in alveolar type II cells.

Low density lipoproteins (LDL) and high density lipoproteins (HDL) from serum stimulate signal-transduction pathways and exocytosis in rat alveolar type II cells. Both LDL and HDL stimulated primary cultures of type II cells to secrete phosphatidylcholine (PtdCho), the major phospholipid component of pulmonary surfactant. The effects on secretion were preceded temporally by stimulation of inositol phospholipid catabolism, calcium mobilization, and translocation of protein kinase C from cytosolic to membrane compartments. Heparin, which blocks the binding of ligands to the LDL receptor, completely inhibited the effects of LDL on signal transduction and PtdCho secretion but did not inhibit the effects of HDL. Unilamellar PtdCho liposomes the size of native LDL had no effect on type II cells; however, PtdCho complexes containing either apolipoproteins E or A-I stimulated both signal transduction and PtdCho secretion. LDL receptors were present in type II cell membranes by immunoblotting. In contrast to findings with hepatic membranes, type II cells exhibited two major bands of 130 kDa and 120 kDa and a minor band at 230 kDa that also was present under reducing conditions. These results are consistent with our hypothesis that the LDL-receptor pathway functions in vivo to deliver cholesterol to type II cells and that this process is coupled to surfactant assembly and secretion via signal-transduction pathway(s). HDL elicits similar responses independent of the LDL receptor, suggesting that type II cells may use the selective uptake pathway to obtain cholesterol or that HDL triggers signal transduction by mechanisms unrelated to lipid delivery.

Adenosine Triphosphate↗