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Biomedical subjects

S Moore

Publications and source records attributed to S Moore.

At least 271 records · Page 15Linked to original sources
PubMed1985

Glycosaminoglycan composition and biosynthesis in the endothelium-covered neointima of de-endothelialized rabbit aorta.

The biosynthesis and composition of glycosaminoglycans (GAG) in the endothelium-covered neointima, formed in response to de-endothelialization of the rabbit aorta by a balloon catheter, was examined. The [14C]glucosamine incorporation into GAG during an in vitro incubation with intimal-medial tissue was monitored periodically up to 24 hr. The GAG were isolated after an exhaustive proteolytic digestion with pronase and protease followed by ethanolic precipitation at 4 degrees C. Electrophoretic migration on cellulose acetate paper was compared for identification. The distribution of GAG was determined after a selective enzymatic digestion of isolated GAG using specific enzymes. Heparan sulfates were estimated after nitrous acid treatment. The concentration of GAG was measured spectrophotometrically by forming colored complexes with Alcian blue dye. In addition, the specific activity (dpm/microgram GAG) and the rate of GAG synthesis (ng/mg dry defatted tissue/day) were determined. The results indicate that the rate of GAG synthesis by de-endothelialized neointima (DEA) was twice that of intact aorta (control). In the re-endothelialized neointima (REA), the GAG synthetic rate was three times more than in control. However, the release of GAG into medium from REA accounts for only 25% of the GAG synthesized by this tissue type, and the release from DEA accounts for 60% of the synthesized GAG. Similarly, a threefold increase in the GAG concentration in REA compared to control was found. The relative distribution as chondroitin-6-sulfate (C6S), chondroitin-4-sulfate (C4S), dermatan sulfate (DS), heparan sulfate (HS) and hyaluronic acid (HA) was markedly altered in the injured neointima. There was an increase in chondroitin sulfates (CS) and DS concomitant with a decrease in HS. It is concluded that injury to aortic endothelium induces stimulation of GAG synthesis in the arterial wall. Furthermore, the greater release of GAG from DEA, compared to control and REA, suggests that endothelium may function as a "reverse" barrier in the neointima covered by regenerated endothelium.

Animals↗
PubMed1985

Proteoglycan distribution in catheter-induced aortic lesions in normolipaemic rabbits. An ultrastructural study.

The aortic lesions induced in normal-fed rabbits by an indwelling catheter were examined for changes in lipid content shown by oil red O-stained sections and associated proteoglycan distribution and ultrastructural changes by transmission electron microscopy of ruthenium red-stained sections, during an 8-week period of regression. Compared to normal aorta there was a highly significant increase in proteoglycan in lipid-containing lesions, which was also associated with the presence of regenerated endothelium. In the lesions which had regressed in terms of size and lipid content, the proteoglycan concentration, especially in superficial regions, was significantly reduced compared to early lesions and was similar to that seen in the normal vessel. Proteoglycan concentration decreased before lipid content of lesions was reduced. Proteoglycan was not associated with lipid-containing macrophages. These observations support the hypothesis that an increased glycosaminoglycan concentration is associated with lipid deposition in the vessel wall in response to injury in the absence of hyperlipaemia.

Animals↗
PubMed1985

Influx of [3H,14C]cholesterol-labelled lipoprotein into re-endothelialized and de-endothelialized areas of ballooned aortas in normal-fed and cholesterol-fed rabbits.

The entry of [3H]- and [3H,14C]cholesterol-labelled lipoprotein into de-endothelialized and re-endothelialized areas of balloon-injured rabbit aortas was studied in normal-fed and cholesterol-fed rabbits. Studies were carried out 11-15 weeks after the initial injury when endothelial regeneration involved approximately half of the aortic area. The entry into the aorta of 3H-labelled free and ester cholesterol in lipoprotein over a 72-h period was studied following the ingestion of a single dose of 3H-labelled cholesterol. The entry of double labelled [3H,14C]cholesterol-labelled lipoprotein was also studied over a 6-h period following the injection of plasma from donor rabbits. The accumulation of cholesterol and cholesterol ester in the aorta in both the normal- and cholesterol-fed rabbits was significantly greater for the re-endothelialized (white) areas than for the de-endothelialized (blue) areas or the sham-operated aortas. Where the rabbits were cholesterol-fed 4-10 times the amount of cholesterol accumulated in re-endothelialized intima compared to normal intima. Both entry (micrograms/day/100 mg wet weight aortic intima) and clearance (mu 1 plasma/day/cm2) of free and ester cholesterol were increased in the neointima compared with the normal intima for both normal-fed and cholesterol-fed rabbits. Hydrolysis of cholesterol ester occurred in the neointima and was greater than in the corresponding de-endothelialized area but less than for the sham-operated intima. Synthesis of cholesterol ester was minimal in all areas. Removal of labelled cholesterol and cholesterol ester from the intima during a 20-h efflux period following the initial 72-h loading period indicated that for aortas of both normal-fed and cholesterol-fed rabbits, there was greater removal for normal intima than for either re-endothelialized or de-endothelialized intima. However, no clear difference between the blue and white areas was observed. It is concluded that the accumulation of cholesterol in neointima after balloon injury is associated with a marked increase in permeability to lipoprotein of the neointima as well as to possible binding of lipoprotein to glycosaminoglycan in the artery.

Animals↗
PubMed1985

Scanning electron microscopy of normal rabbit aorta: injury or artifact?

The reported morphology of both normal and "injured" aortic endothelium differs significantly from one study to another. To better understand these disparities, we examined the effects of manipulating the preperfusion conditions on the subsequent morphology of normal aortic endothelium in the rabbit. Glutaraldehyde perfusion without any preperfusion with an electrolyte solution, induced vasoconstriction and the accumulation of cellular and plasma protein on the luminal surface of the aorta. Prolonged preperfusion by Ringer-Locke solution and to a lesser extent, by Krebs-Henzleit solution or modified Eagles medium, induced changes in the endothelium similar to those reported as the response to injury induced by other stimuli. Profound vessel wall alterations also occurred in animals which were shocked (through acute blood loss) or killed (by overdose of anesthetic) prior to fixation. These observations may explain, in part, the discrepancies in previous descriptions of the appearance of "normal" rabbit aortic endothelium in SEM, and suggest that the type and duration of the preperfusion must be considered to avoid morphological artifacts.

Animals↗
PubMed1985

Pathogenesis of atherosclerosis.

There is abundant evidence that changes in diet and various types of vessel wall injury can independently induce the growth of arterial lesions in experimental animals. These lesions closely resemble those found in humans with atherosclerosis. Whether endothelial injury or accumulation of lipoprotein in the arterial intima is the initial event, the progression of the disease is characterized by changes in the neointima that favor the deposition of lipid. The metabolism of proteoglycans may be especially important in this process; this is relevant to diabetes because changes in proteoglycan metabolism are associated with this disease. Insulin and growth hormone may favor the proliferation of smooth muscle cells in the arteries of diabetic patients. Many agents, which are potentially injurious to the endothelium, accentuate the response of the vessel wall to injury. Modifications of the thrombotic process, such as increased production of thromboxane by platelets, decreased production of prostacyclin by the endothelium, and increased production of von Willebrand factor further enhance the thrombotic process and may be important in the initiation and subsequent progression of atherosclerosis in diabetics. Alterations in lipoprotein metabolism may also facilitate the development of endothelial injury.

Animals↗
PubMed1985

Cerebral effects of isovolemic hemodilution with a hypertonic saline solution.

In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR: Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 +/- 6 mEq/liter and 320 +/- 5 mOsm/kg, respectively, mean +/- standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 +/- 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 +/- 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.

Animals↗
PubMed1985

Experimental carbon dioxide laser brain lesions and intracranial dynamics: Part 2. Effect on brain water content and its response to acute therapy.

Experimental brain lesions were created over the left parietooccipital cortex of the albino rabbit through the intact dura mater with high radiating carbon dioxide laser energy (40-W impact, 0.5-second duration, for a total time of 4 seconds on a 12.5-mm surface). The brain water content was studied 2, 6, and 24 hours after the insult. Another two groups of animals received acute therapy with either dexamethasone (1 mg/kg) or furosemide (1 mg/kg). In all groups, Evans blue extravasation uniformly extended from the impact crater into the surrounding white matter. The brain water content in the gray matter was elevated from the control value by 2 hours after impact (P less than 0.005) and remained elevated at 6 and 24 hours. The white matter brain water content did not increase until 6 hours after impact and remained elevated in the 24-hour group (P less than 0.005). After dexamethasone treatment, there was a significant decrease of water in the gray matter (P less than 0.01), but not in the white matter. With furosemide therapy, there was no reduction of gray or white matter brain water.

Animals↗
PubMed1984

Proteoglycan distribution in rat aortic wall following indwelling catheter injury.

The morphologic response of the aortic wall of the normal fed rat to intimal injury by an indwelling catheter in place for 3 weeks was examined at the time of removal of the catheter and 4, 8, and 26 weeks later. Changes in the concentration of glycosaminoglycan were assayed morphometrically in ruthenium red-stained sections examined by transmission electron microscopy. Two types of ruthenium red-positive granules were identified in the intercellular matrix; large (greater than 20 nm), containing chondroitin sulphate and small (less than 20 nm) containing heparan sulphate. Endothelial denudation and some thrombus seen at the time of removal of the catheter, was associated with a decrease in the concentrations of both types of granules in the subendothelial space compared to normal rats. At later time intervals there was neointimal thickening containing no lipid, and occasional small areas of lipid accumulation. Compared to normal rats there was no significant change in granule concentration in the subendothelial space at any time interval. There was a slight increase in the concentration of large granules of the deep neointima at the time of removal of the catheter and after 4 weeks. In lipid-containing areas there was a highly significant increase in large granule concentrations compared to normal or to intimal thickening without lipid. The observations support the possibility that lipid accumulation is related to an increase in glycosaminoglycan concentration.

Animals↗
PubMed1984

A mouse monoclonal antibody with anti-A,(B) specificity which agglutinates Ax cells.

A hybridoma (ES-15) was obtained by fusing the NS-1 cell line with spleen cells from a mouse immunised with soluble blood group A2 substance. The cloned hybridoma culture supernatant was shown to contain an IgM class antibody which strongly agglutinates group A cells and weakly agglutinates group B cells. The serological specificity of this antibody is described as anti-A,(B) in this report. The abilities of unconcentrated monoclonal anti-A,(B), a commercial human polyclonal anti-A,B (group O serum) and a commercial monoclonal anti-A reagent to detect 15 examples of Ax cells were compared by both slide and tube techniques. Using a slide technique monoclonal anti-A,(B) agglutinated 14 examples of Ax cells, human anti-A,B 2 examples, while monoclonal anti-A failed to detect any of the Ax cells tested. Similar differences in the reactivity of the three antibodies were observed using a tube technique. Data are also presented which show that a 1:1 (v/v) mixture of monoclonal anti-A,(B) with a monoclonal anti-B reagent is an effective replacement for human anti-A,B in ABO grouping procedures.

ABO Blood-Group System↗
PubMed1984

Rheumatoid arthritis in Lesotho.

Thirty-nine black African patients were seen with probable, definite or classical rheumatoid arthritis (RA); 32 of these were seen in a prospective study out of a total of 15 834 new patients 15 years and older at presentation seen in a 12-month period. The diagnosis was based on the American Rheumatism Association criteria for RA or the Rome criteria for inactive RA. The high incidence of severe disease as well as the occurrence of advanced disease in young patients is notable. 80% of the patients came from rural areas. Radiological lesions were found in 74% and serological abnormalities in 92%. Rheumatoid factor (RF) was found to be positive in 12% of an age and sex matched control group and in 19% of a group of patients suffering from tuberculosis.

Adolescent↗
PubMed1984

Ultrastructural changes in re-endothelialized and non-endothelialized rabbit aortic neo-intima following re-injury with a balloon catheter.

The response by normal rabbit aortas to the removal of the endothelium with a balloon catheter, was compared to the response to the removal of regenerated endothelium from rabbit aortas that had been previously de-endothelialized. De-endothelialization results in the formation of a neo-intima. Thrombus formation following a second balloon catheter injury was compared among injured neo-intima that had been re-endothelialized, non-re-endothelialized neo-intima, and the subendothelium of normal vessels following a single injury. Rabbit aortas were examined by scanning electron microscopy of full circumference segments of the aorta and by transmission electron microscopy. Thirty minutes after a single de-endothelialization injury with a balloon catheter the luminal surface is covered by a monolayer of platelets adhering to the subendothelial connective tissues. Two weeks later there is neo-intimal formation and endothelial regeneration around branch vessel orifices. The remainder of the luminal surface is composed of smooth muscle cells (SMC). A balloon catheter injury to a vessel injured 2 weeks previously results in fibrin formation and platelet-fibrin microthrombi on the aortic intimal surface. The response of the aortic wall to re-injury does not seem to be related to the prior existence of endothelium. Both single and repeated injuries result in a distribution of formed elements which may depend, in part, on haemodynamic factors.

Animals↗
PubMed1984

Evaluation of monoclonal antibodies to blood group A.

Balb/c mice were immunized with human blood-group A2 active cyst fluid glycoprotein. Fusion of spleen cells with NS-1 myeloma cell line produced a total of 11 blood group antibody secreting hybridomas of which seven were apparently specific for blood-group A and were subjected to further evaluation. Of these 2 were IgM class and 5 IgG class. Two anti-A supernatants showed a significant decrease in avidity time against A2B cells when ionic strength was increased to 0.25. Tube titres of all anti-A supernatants were unaffected by ionic strength. pH had no effect on the avidity time or tube titre of any of the antibodies tested. The supernatant from one hybrid (ES-9) was selected for further evaluation as a blood grouping reagent. This supernatant had a tube titre of 1:128 and was used without concentration for comparison of its serological reactivity with two examples of commercial monoclonal anti-A and one example of human anti-A. Monoclonal anti-A (ES-9) was found to be a potentially useful red cell grouping reagent.

ABO Blood-Group System↗
PubMed1984

A monoclonal antibody to human blood group B. Performance, evaluation and optimisation.

A monoclonal anti-B antibody (ES-4) was obtained by fusing spleen cells from a mouse immunized with soluble human blood group B substance with mouse myeloma cell line NS-1. The antibody was shown to agglutinate optimally group B cells at pH 7.2 and 0.15 ionic strength. Increasing the ionic strength to 0.24 gave optimal reactivity over a wider pH range. Culture supernatant containing anti-B (ES-4), after pH and ionic strength adjustment could be used in unconcentrated form as a red cell typing reagent. Anti-B (ES-4) agglutinated five examples of cells of the Bweak (Bw) phenotype and one example of acquired B phenotype. In contrast three of the Bw cells and the acquired B phenotype were not agglutinated by a commercial monoclonal anti-B by a tube technique. The data suggested that the equilibrium constant of the monoclonal anti-B (ES-4) was higher than that of the commercial reagent.

ABO Blood-Group System↗
PubMed1984

Adenosquamous carcinoma of the liver arising in biliary cystadenocarcinoma: clinical, radiologic, and pathologic features with review of the literature.

Primary biliary cystadenoma, cystadenocarcinoma, squamous carcinoma, and adenosquamous carcinoma of the liver are rare tumors. We describe a middle-aged woman with recurrent fever and a clinical diagnosis of hepatic abscess who proved at laparotomy to have adenosquamous carcinoma of the liver arising in a biliary cystadenocarcinoma. The pathologic features of the tumor and findings on ultrasonography, angiography, and computed tomography are described in detail. The pathogenetic relationships of this unusual tumor to chronic biliary inflammation, biliary cystadenoma, and cystadenocarcinoma and to bile duct malformations (von Meyenburg complexes) are considered.

Adenocarcinoma↗