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At least 181 records · Page 10Linked to original sources
PubMed1983

T cell responses induced by the parenteral injection of antigen-modified syngeneic cells. I. Induction, characterization, and regulation of antigen-specific T helper cells involved in delayed-type hypersensitivity responses.

This report presents evidence for the role of antigen-specific helper T cells in augmenting the in vivo development of delayed-type hypersensitivity (DTH) responses to both hapten and protein antigens. The role of these helper T cells in the in vivo induction and regulation of DTH responses was investigated. Mice were primed subcutaneously with optimal numbers (3 X 10(7)) of either protein antigen- or TNP-modified syngeneic spleen cells. Primed spleen or lymph node cells, but not thymocytes or unprimed cells, were found to significantly augment the DTH response of syngeneic recipients injected subcutaneously with suboptimal numbers (1 to 2 X 10(6)) of antigen-modified syngeneic cells. Primed spleen or lymph node cells augmented both in vivo ear swelling reactions and in vitro antigen-induced T cell proliferative responses in recipient animals. The helper effect was found to be mediated by a population of radioresistant, Thy-1+, Lyt-1+2-, I-A+ cells, a phenotype identical to that of antigen-specific Tprlf cells found in primed lymph nodes. In contrast, effector TDH cells were found to be Thy-1+, Lyt-1+2-, I-A- cells. Splenic T cells from TNP-primed mice augmented TNP-specific DTH responses, but not DTH to irrelevant protein antigens, and vice versa. Helper T cell induction correlated with the presence of H-2 I-region determinants on the inducer cells, because antigen-modified spleen cells were the most efficient inducers, modified thymocytes were less efficient, and modified erythrocytes were ineffective. Mapping studies also indicated that I-region identity between the antigen-modified spleen cell immunogen and the Th donors was both necessary and sufficient for DTH Th cell induction. In addition, functional helper T cell activity could be both specifically tolerized and suppressed by the transfer or suppressor T cells raised by the i.v. injection of antigen-modified syngeneic cells.

Animals↗
PubMed1981

[Effect of tyrosine-74-modified cytochrome C on electron transfer in Keilin-Hartree submitochondrial particles].

The tyrosine-74 modified cytochrome c is obtained by the interaction of cytochrome c with N-(2, 2, 5, 5-tetramethyl-3-carboxy-piroline-oxyl) Imidazol. The absorbtion spectrum of the modified derivative at the visible region does not differ substantially from the native protein. The band of absorbtion at 695 nm, which shows that the performed modification is soft and the conformation of the modified cytochrome c is close to that of the native protein. Redox potential of the modified cytochrome c, determined by spectrophotometric titration, does not differ from that of the native protein. Submitochondrial particles, deficient of cytochrome c, are reconstructed with modified protein. In both substrates of biologic oxidation succinate and ascorbate the electron transport is restored by the modified protein in considerably higher concentrations than those of the native cytochrome c. Inspite of small conformation differences and unchanged redox potential of the modified cytochrome c substantial differences are observed in its electron-carrying properties as well as its interaction with the membrane cytochrome c reductase and oxydase.

Animals↗
PubMed1980

Hemodynamic and clinical comparison of the Hancock modified orifice and standard orifice bioprostheses in the aortic position.

Bioprosthetic aortic valve replacement in patients with a small aortic root has been associated with postoperative transvalvular gradients. A modified orifice Hancock xenograft bioprosthesis has been developed and is purported to increase significantly the effective orifice area (as evaluated by in vitro testing) compared to the standard orifice Hancock bioprosthesis. To assess the in vivo differences, we compared 481 patients with standard orifice prostheses with 156 patients with modified orifice prostheses. Postoperative catheterization was performed in 24 patients with modified orifice (valve diameters 19 to 25 mm) with 14 with standard orifice valves (valve diameters 21 to 25 mm). Actuarial rates of survival, valve failure, endocarditis, and thromboembolism did not differ significantly between the two subgroups. Peak aortic valve gradients on the whole were less in the modified orifice subgroup than in the standard origice subgroup (12 +/- 1 torr versus 20 +/- 6 torr [mean +/- SEM]), but the difference was not statistically significant (p greather than 0.05). The calculated in vivo aortic valve areas were slightly, but insignificantly, greater in the modified orifice subgroup than in the standard orifice subgroup (p greater than 0.05). These in vivo data partially corroborate the in vitro findings of increased effective orifice area and internal-to-external diameter ratio for the modified orifice bioprosthesis. The hemodynamic differences between the two valve types are small, however, and the putative clinical advantages inherent in the use of the modified orifice bioprosthesis remain to be completely defined.

Aortic Valve↗
PubMed1995

A prospective trial comparing the efficacy and complications of the modified Dornier HM3 and MFL 5000 lithotriptors for solitary renal calculi.

A prospective randomized study of 198 patients was conducted to compare the efficacy of the modified Dornier HM3 lithotriptor to the MFL 5000 lithotriptor. Entrance criteria included solitary stones at any location within the upper collecting system that had not previously been treated with lithotripsy. Following lithotripsy the patients were evaluated by a blinded radiologist with a plain abdominal film, tomograms and renal ultrasound at 1, 4 and 12 weeks. Patients were classified at 12 weeks after lithotripsy as failing treatment if any stone fragments were imaged. Of the patients 170 were available for complete 3-month followup. No statistical or clinical difference in stone-free rates was apparent for calculi in the ureter or renal pelvis in either group. Of patients with lower caliceal stones 80% had no residual fragments visualized at 12 weeks when treated with the modified HM3 device versus 56% with the MFL 5000 lithotriptor (p = 0.05). Treatment time on the MFL 5000 unit was significantly prolonged compared with the modified HM3 device (0.7 hours versus 0.4 hours, respectively) resulting in fewer patients being treated in a given day (p < 0.001). No statistical difference in complication rates could be found between the 2 machines. Steinstrasse were noted in 10% of the patients treated with the modified HM3 device and 6% of the MFL 5000 group. Subcapsular hematomas were noted in 4% of the MFL 5000 treatment arm compared to 1% in the modified HM3 group. Overall, the MFL 5000 lithotriptor was believed to offer no significant clinical advantage over the modified HM3 device in terms of lithotripsy efficacy, although the multifunctional table did offer more versatility for stone treatment. For a busy lithotripsy center, the modified HM3 lithotriptor is still the most efficacious.

Adult↗
PubMed1976

[A new modified wick catheter for measurement of the brain tissue pressure-an evaluation of static and dynamic properties of the catheter (author's transl)].

The interstitial pressure of the brain was measured with wick catheter by Lassen in 1972. But original wick catheter inserted into the brain tissue does not always measure the real interstitial pressure as indicated by experimental results of Brodersen, because, the interstitial pressure is always affected by solid pressure such as cells in the brain tissue, in the condition of which surrounded by positive CSF pressure in the semiclosed skull box. It is not yet clarified what kinds of the pressure are measured by wick catheter method in the brain tissue. The size of wick catheter is 300-500 times as large as the width of interspace of the brain tissue and the catheter is easily obstructed by brain tissue. Therefore, a new, modified wick catheter is made for improvement of these problems which is observed by using original wick catheter. The new, modified catheter has 0.4 mm inside diameter and 10 cm length. The tip of catheter is closed and 6 small side holes(0.1 mm0)are made. Inside the catheter, several pieces of 0.04 mm diameter nylon threads are inserted as shown in figure 1, and the catheter is filled up with the cerebrospinal fluid. In this paper, the structure of the new, modified catheter is demonstrated, and the brain tissue pressure is measured, comparing with the results of the original wick catheter to test the function of the new, modified catheter. The results of measurement of the brain tissue fluid pressure with the new, modified catheter are as follows; 1) The brain tissue fluid pressure is relatively constant and shows a positive pressure of 5.2 mmHg. 2) As there are few blocking effects in the catheter, the new, modified catheter is useful for the measurement of the brain tissue fluid pressure for a long time. 3) The brain tissue fluid pressure is not altered by the number's of nylon threads in the catheter at static condition, but movement of brain tissue fluid pressure with respiration is a little dumped by the increased conductancy with the numbers of nylon threads in the catheter. 4) The tissue fluid pressure affected by the viscosity and osmolarity of the fluid in the catheter, CSF should be used for correct measurement. According to these results, it might be concluded that the new, modified wick catheter is better than the original wick catheter regarding prevention of obstruction of the catheter by brain tissue fragments, artifacts which causet by movement of wick fibers, measurement of brain tissue fluid pressure for a long time and clarify the resistance of catheter to pressure conductancy.

Animals↗
PubMed1981

Alternative conformations of DNA modified by N-2-acetylaminofluorene.

Modification of DNA by the carcinogen N-acetoxy-N-2-acetylaminofluorene gives two adducts, a major one at the C-8 position of guanine and a minor one at the N-2 position with differing conformations. Binding at the C-8 position results in a large distortion of the DNA helix referred to as the "base displacement model" with the carcinogen inserted into the DNA helix and the guanosine displaced to the outside. The result is increased susceptibility to nuclease S1 digestion due to the presence of large, single-stranded regions in the modified DNA. In contrast, the N-2 adduct results in much less distortion of the helix and is less susceptible to nuclease S1 digestion. A third and predominant adduct is formed in vivo, the deacetylated C-8 guanine adduct. The conformation of this adduct has been investigated using the dimer dApdG as a model for DNA. The attachment of aminofluorene (AF) residues introduced smaller changes in the circular dichroism (CD) spectra of dApdG than binding of acetylaminofluorene (AAF) residues. Similarly, binding of AF residues caused lower upfield shifts for the H-2 and H-8 protons of adenine than the AAF residues. These results suggest that AF residues are less stacked with neighboring bases than AAF and induce less distortion in conformation of the modified regions than AAF. An alternative conformation of AAF-modified deoxyguanosine has been suggested based on studies of poly(dG-dC).(dG-dC). Modification of his copolymer with AAF to an extent of 28% showed a CD spectrum that had the characteristics of the left-handed Z conformation seen in unmodified poly(dG-dC).poly(dG-dC) at high ethanol or salt concentrations. Poly(dG-dC).poly(dG-dC) which does not undergo the B to Z transition at high ethanol concentrations, did not show this type of conformational change with high AAF modifications. Differences in conformation were suggested by single-strand specific nuclease S1 digestion and reactivity with anticytidine antibodies. Highly modified poly(GS-dC).poly(DG-dC) was almost completely resistant to nuclease S1 hydrolysis, while, modified DNa and poly(dG).poly(dC) are highly susceptible to digestion. Two possible conformations for deoxyguanosine modified at the C-8 position by AAF are compared depending on whether its position is in alternating purine-pyrimidine sequences or random sequence DNA.

2-Acetylaminofluorene↗
PubMed1995

Malondialdehyde-modified HDL leads to accumulation of cholesterol in rat liver endothelial cells.

In order to study in vivo the effect of modified high density lipoprotein (HDL) on the movement of free cholesterol to liver cells and bile, we injected i.v. into rats, native or malondialdehyde modified HDL labelled with [14C]cholesterol. Bile analysis indicated that the contribution of labelled cholesterol to bile acid secretion was diminished in the group receiving MDA-modified HDL when compared to control group. On the other hand, the liver analysis revealed higher radioactivity in the treated group. A separation of liver cells into parenchymal, endothelial, and kupffer at 90 min after the injection of MDA-modified HDL or native HDL indicated that the endothelial cell uptake of labelled free cholesterol from MDA-modified HDL was 2.6-fold higher than for native HDL. It is suggested that liver endothelial cells may be involved in the protection against atherogenoic oxidized lipoprotein. However, with regard to our finding, the uptake of cholesterol from modified HDL was detrimental to bile acid secretion.

Animals↗
PubMed1982

Modified axonemes and ciliary membranes in three polychaete species.

In living Ophryotrocha puerilis, Polyophthalmus pictus and Dinophilus gyrociliatus no modified cilia are present. Treatment with hyper- and hypotonic magnesium chloride solutions leads to the formation of either cilia with dilated tips or discocilia (paddle cilia). Discocilia show axoneme loops within distal swellings of the ciliary membranes. Both types of modified cilia regain their normal appearance if they are allowed to recover in seawater. The total number of discocilia and the diameter of the loops are inversely related to the osmolarity of the magnesium chloride solution used. Even isotonic solutions of magnesium chloride, which are usually used to anaesthetize marine worms, readily induce modified cilia. This indicates that the effect is not merely due to osmotic conditions. Glutaraldehyde and osmium tetroxide may act in the same way to induce modified cilia, a fact which may account for the numerous TEM and SEM documentations of modified cilia in various marine invertebrates. Which cilia in a particular species are modified varies from one specimen to another.

Animals↗
PubMed1991

Interaction of 4-aminopyridine with normal and chloramine-T-modified K channels of neuroblastoma cells.

The steady-state effects and rate of action of 4-aminopyridine (4-AP) on normal and chloramine-T (CL-T)-modified voltage-dependent potassium (K) currents were studied in neuroblastoma cells with the whole-cell voltage-clamp current recording technique. 4-AP apparently slows both the activation and inactivation of the normal current but does not modify the time course of the CL-T-modified current. These differential effects of 4-AP are interpreted as resulting from the existence of two types of K channels with different 4-AP sensitivities under normal conditions and similar 4-AP sensitivities after CL-T, which furthermore slows their inactivation [8, 9]. While the onset of 4-AP action on the normal current is delayed and can be described by the difference of two exponentials, the onset of 4-AP action on CL-T-modified current starts immediately after the external application of the drug and can be described by the sum of two exponentials. The 4-AP-induced block of the normal current exhibits use-dependent features and is relieved by long conditioning depolarizations. In contrast, the block of the CL-T-modified current is not use-dependent. At high 4-AP concentrations (1-10 mM), the steady-state block of the normal current reaches a saturating value of 95%, while the steady-state block of the CL-T-modified current and the "unblocked" normal current only reaches a saturating value of 35%. The results suggest that CL-T inhibits a channel or membrane constituent which contributes to the inactivation of channels and increases their apparent affinity for 4-AP when they are in closed or open states.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1983

Identification of a locus modifying the electrophoretic mobility of malate dehydrogenase isozymes in incense-cedar (Calocedrus decurrens), and its implications for population studies.

Using megagametophyte (maternal haploid) and embryo (diploid) tissues of incense-cedar seeds, the expression of one of three malate dehydrogenase (MDH) loci was found to be influenced by a second, unlinked, modifier locus. Whereas alleles of the affected structural locus are codominant, the modifier alleles show dominance. The action of the modifier, limited to 1 of 28 structural loci examined, results in a shift of electrophoretic mobility detectable in conventional starch gels. Both the structural and the modifier MDH loci are polymorphic in all populations surveyed. Studies of genetic variation in natural populations made without rigorous genetic analysis may not detect such modification. By misinterpreting the genetic basis of enzyme phenotypes, such undetected modification can result in overestimates of genetic diversity in natural populations and can cause an apparent excess of homozygotes relative to expectations. These effects on allele and genotype frequency estimates are dependent on the levels of polymorphism at both the structural and the modifier loci. Using procedures common to many surveys of electrophoretic variation, the frequency of a recessive modifier allele could be as high as 0.3 before being detected.

Electrophoresis↗
PubMed1988

Differential effect of food on kinetics of bromocriptine in a modified release capsule and a conventional formulation.

The influence of food on release of drug from a modified release capsule of bromocriptine 5 mg (Parlodel SRO) and a conventional formulation of bromocriptine 5 mg has been studied in 8 healthy male volunteers. Both formulations produced objective and subjective effects, such as orthostatic reactions, nausea, dizziness, vomiting and nasal congestion. The modified release capsule caused fewer side-effects than the normal capsule. Both formulations had less cardiovascular effect in the fed than in the fasting state. There was no significant difference between the normal and the modified release capsules taken fasting or after a meal in terms of the AUC extrapolated to infinity. The relative bioavailability of the 5 mg modified release capsule was 84.6% of the normal capsule under fasting conditions and 107.5% after food. In contrast to the virtually unchanged extent of absorption, the rate of absorption was markedly affected by food, especially from the conventional capsule. The mean time of 50% absorption increased from 1.06 h (fasting) to 3.2 h (fed), whereas for the modified release capsule food mainly resulted in an increased lag time of absorption. The almost instantaneous dissolution of bromocriptine from the normal capsule in vitro (both in HCl and fasting human gastric juice) and the delay of absorption after a meal in vivo suggest that the rate limiting step in absorption of the normal capsules is delivery of released drug from the stomach to the small intestine, which is delayed by food. Both the modified release 5-mg capsule and the normal 5-mg capsule showed extended suppression of prolactin over 36 h, in all subjects, both fasted and after a meal.

Adult↗
PubMed1988

Pharmacokinetics of low-dose oral modified release, soluble and intravenous aspirin in man, and effects on platelet function.

The pharmacokinetics of low-dose aspirin and the resulting salicylic acid were studied in 6 healthy volunteers. Each received a single 50-mg dose of (1) oral modified release capsules, (2) oral solution and (3) intravenous solution. The volunteers also received 50 mg modified release capsules daily for 6 days to determine the effect on collagen, ADP and arachidonate induced platelet aggregation and thromboxane production, and to compare the pharmacokinetics after repeated dosing with the parameters obtained after the single dose. The formulation and route of administration profoundly influenced several pharmacokinetic parameters for aspirin: the maximum concentration (Cmax, ng.ml-1) was 221 and 191 after modified release for single and chronic dosing respectively, 1323 after the oral solution and 6000 after intravenous injection; the time to achieve this maximum concentration (tmax, h) was 3.42 and 3.02 after modified release for single and chronic dosing respectively, and 0.29 after the oral solution; the area under the plasma drug concentration versus time curve (AUC, microgram.h.ml-1) was 0.38 and 0.27 after modified release single and chronic dosing respectively, 0.68 after the oral solution and 1.57 after intravenous injection. The elimination of aspirin after the two solutions was at least biphasic. The terminal phase rate constant ranged from 1.52 h-1 after intravenous injection to 1.88 h-1 after the oral modified release form. The absorption of the oral forms of aspirin was complete as reflected by the total recovery of the doses as salicylic acid in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1981

Effect of chemical modifiers of amino acid residues on proton conduction by the H+-ATPase of mitochondria.

The effect of chemical modifiers of amino acid residues on the proton conductivity of H+-ATPase in "inside out" submitochondrial particles has been studied. Treatment of submitochondrial particles prepared in the presence of EDTA (ESMP) with the arginine modifiers, phenylglyoxal or butanedione, or the tyrosine modifier, tetranitromethane, caused inhibition of the ATPase activity. Phenylglyoxal and tetranitromethane also caused inhibition of the anaerobic release of respiratory delta micro H+ in ESMP as well as in particles deprived of F1 (USMP). Butanedione treatment caused, on the contrary, acceleration of anaerobic proton release in both particles. The inhibition of proton release caused by phenylglyoxal and tetranitromethane exhibition in USMP a sigmoidal titration curve. The same inhibitory pattern was observed with oligomycin and with N,N'-dicyclohexylcarbodiimide. In ESMP, relaxation of delta micro H+ exhibited two first-order phases, both an expression of the H+ conductivity of the ATPase complex. The rapid phase results from transient enhancement of H+ conduction caused by respiratory delta micro H+ itself. Oligomycin, N,N'-dicyclohexylcarbodiimide, and tetranitromethane inhibited both phases of H+ release, and butanedione accelerated both. Phenylglyoxal inhibited principally the slow phase of H+ conduction. In USMP, H+ release followed simple first-order kinetics. Oligomycin depressed H+ release, enhanced respiratory delta micro H+, and restored the biphasicity of H+ release. Phenylglyoxal and tetranitromethane inhibited H+ release in USMP without modifying its first-order kinetics. Butanedione treatment caused biphasicity of H+ release from USMP, introducing a very rapid phase of H+ release. Addition of soluble F1 to USMP also restored biphasicity of H+ release. A mechanism of proton conduction by Fo is discussed based on involvement of tyrosine or other hydroxyl residues, in series with the DCCD-reactive acid residue. There are apparently two functionally different species of arginine or other basic residues: those modified by phenylglyoxal, which facilitate H+ conduction, and those modified by butanedione, which retard H+ diffusion.

Adenosine Triphosphatases↗
PubMed1980

The sulphatase of ox liver. XXIII. The nature of substrate-modified sulphatase A.

An improved method is described for the preparation of milligram quantities of substrate-modified sulphatase A. The latter has the same molecular weight and the same ability to form a tetramer as has native sulphatase A. It has been shown that the modified enzyme prepared with nitrocatechol [35S]sulphate as substrate contains 1 mol 35SO24- per mol enzyme and that any treatment which causes reversion of the modified enzyme to native enzyme is accompanied by the loss of the bound SO24-. Dialysis of the 35S-modified enzyme against a solution containing SO24- causes a loss of 35SO24- with no change in the amount of modified enzyme in the preparation. It has been shown that the activation of the substrate-modified enzyme by SO24- does not lead to the formation of a third stable form of sulphatase A.

Animals↗
PubMed1977

Preparation and enzymatic hydrolysis of dinucleoside monophosphates and DNA modified with aromatic residues.

The following procedures have been used to prepare fifteen modified dinucleoside monophosphates: (a) bisulfite-catalyzed transamination with aniline to give an N4-phenylcytidine (CPh), (b) bisulfite-catalyzed transamination with beta-naphthylamine to give an N4-beta-naphthylcytidine (CbetaN), (c) alkylation with 7-bromomethylbenz[a] anthracene to afford a 7(benz[a]anthryl-7-methyl)guanosine (GMBA), and (d) reaction with N-acetoxy-2-acetylaminofluorene to give an 8-(N-2-fluorenylacetamido)guanosine (GAAF). The compounds prepared were A-CPh, CPh-A, CPh-G, U-CPh, CPh-U, A-CbetaN, CbetaN-A, G-CbetaN, CbetaN-G, U-CbetaN, CbetaN-U, GMBA-U, U-GMBA, GAAF-U, and U-GAAF. All of the modified compounds were hydrolyzed to the expected monomers with venom and spleen exonucleases. Hydrolysis by micrococcal nuclease was inhibited in the following cases: A-CPh, A-CbetaN, U-GMBA, and U-GAAF. The first three reactions above were applied to denatured calf thymus DNA to prepare modified DNA samples containing from 0.3 to 2.0% bound aromatic residues. The modified nucleic acids were completely hydrolyzed to nucleosides by the combination of venom exonuclease, deoxyribonuclease I and alkaline phosphatase. The same results were obtained with a combination of spleen exonuclease, deoxyribonuclease II, and alkaline phosphatase. Hydrolysis of the modified nucleic acids by micrococcal nuclease and alkaline phosphatase afforded primarily nucleosides, with some dinucleoside monophosphates. The amount of the latter did not exceed that found in the hydrolysis of control DNA, however. Other workers have observed inhibition of enzymatic hydrolysis of nucleic acids modified by aromatic carcinogens. We postulated that their results may have been caused by cross-links, which were avoided in our studies.

Animals↗
PubMed1991

Survival and differentiation within the adult mouse striatum of grafted rat pheochromocytoma cells (PC12) genetically modified to express recombinant beta-NGF.

Rat pheochromocytoma PC12 cells were genetically modified in vitro to express recombinant beta-nerve growth factor (beta-NGF) using a replication-deficient retroviral vector carrying the mouse beta-NGF gene and subsequently implanted into the striatum of a mouse model of Parkinson's disease. The fate of the genetically modified PC12 cells (PC12N.8) was assessed at varying times postimplantation by studying immunoreactivity (IR) to tyrosine hydroxylase (TH) or the rat NGF receptor (NGFR). In vitro, the genetically modified PC12 cells displayed a neuronal morphology in the absence of exogenous NGF which was characterized by extensive neurite outgrowth. In addition, the genetically modified PC12 displayed a catecholaminergic phenotype in vitro as assessed by TH-IR. Following implantation into the striatum, the survival of PC12N.8 cells was limited. Surviving cells could be identified by NGFR-IR, but not by TH-IR. In addition, PC12N.8 cells with a neuronal morphology similar to that observed in vitro were only rarely observed in vivo. No tumors were observed in PC12N.8 graft recipients up to 30 days postimplantation. In contrast, intrastriatal tumors were observed in 50% of the PC12 cell recipients. These data demonstrate that PC12 cells genetically modified in vitro to synthesize beta-NGF do not revert to the mitotic phenotype of the parent PC12 cell line following implantation into the adult striatum, an observation that suggests that these cells may continue to express recombinant beta-NGF in vivo. The data further suggest that the genetically modified PC12 cells lose the catecholaminergic phenotype following implantation into the striatal parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Gland Neoplasms↗
PubMed1988

Quantification of plasma lipids and apolipoproteins in British Halflop rabbits. A comparison between normocholesterolemic rabbits, hypercholesterolemic rabbits (modified WHHL rabbits) and rabbits fed an atherogenic diet.

We have established isolation methods and developed electroimmunoassays for rabbit apolipoprotein A-I (apo A-I), apo B, apo C-III and apo E. The assays were used to characterize a hyperlipidemic strain of the British Halflop rabbits (BHL rabbits), obtained after cross-breeding with WHHL rabbits and referred to as modified WHHL rabbits, and to investigate the changes in the apolipoprotein levels induced by feeding normal BHL rabbits an atherogenic diet (0.25% cholesterol and 3% coconut oil). The modified WHHL rabbits were characterized by increased levels of apo B, apo C-III and apo E as well as cholesterol, phospholipids and triacylglycerol as compared to chow-fed BHL rabbits, while the apo A-I levels were only half of those found in the chow-fed animals. The modified WHHL rabbits had virtually no low density lipoprotein (LDL) receptor activity and a low fractional catabolic rate (FCR) of LDL. These results indicate that the modified WHHL rabbit has the homozygous form of the LDL receptor deficiency. The BHL rabbits fed the atherogenic diet showed increased levels of cholesterol, triacylglycerol, apo B, apo C-III and apo E, as compared to those of the chow-fed BHL rabbits. The apo E and apo C-III reached levels in the range of or even higher than those of the modified WHHL rabbits. The apo A-I levels on the other hand did not differ from those of the chow-fed rabbits. Feeding an atherogenic diet led to a decrease in the FCR of LDL to a level similar to that found in the modified WHHL rabbits.

Animals↗
PubMed1986

The standardisation of gauge length: its influence on the relative extensibility of natural and chemically modified pericardium.

Cyclic uniaxial load tests were performed on natural and chemically modified bovine pericardium which is used in the construction of heart valve substitutes. A template was employed to select specimens from the same sites in different pericardial sacs. When the pericardium was chemically modified by glutaraldehyde fixation as an entire sac the tissue showed increased extensibility after modification compared with the natural tissue. The undeformed stress-free length (gauge length) in both the natural and modified tissue was determined by a highly reproducible experimental method giving a coefficient of variation of less than 0.5%. Specimens excised from a natural pericardial sac demonstrated a significant increase (p less than 0.03) in length, 4.97 +/- 3.49%, after a single load cycle, compared with controls placed in isotonic saline but not mechanically tested. The test pieces had returned to their original length by 8.5 h after the mechanical test. After fixation the same specimens decreased significantly in length (p less than 0.001) by 11.18 +/- 4.28%. This shrinkage was not significantly different to that of the control specimens (11.09 +/- 2.47%) which had not been tested. Uniaxial loading of these chemically modified strips demonstrated a similar increase in tissue extensibility compared to the natural tissue if the undeformed length of the test specimen after shrinkage was used as the gauge length. After mechanical conditioning the chemically modified tissue also demonstrated a significant increase (p less than 0.001) in stress-free length (5.35 +/- 0.59% after 36 cycles, 8.92 +/- 1.50% after 2085 cycles). These deformations were not permanent. The tissue had returned to its original length after 38 h in its normal buffered glutaraldehyde storage medium. On the basis of these observations, recommendations for the clarification and standardisation of gauge length definitions were made in natural, chemically modified and mechanically conditioned tissue.

Animals↗