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At least 19 recordsLinked to original sources

PubMed1993

In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) to apolipoprotein AI in rabbits.

In vivo conversion of recombinant human proapolipoprotein AI (rh-Met-proapo AI) from E. coli to apolipoprotein (apo) AI was investigated. rh-Met-proapo AI was labeled with 125I, and then administered intravenously to rabbits. Blood was sampled periodically for 6 days. The plasma decay curves of radioiodinated rt-Met-proapo AI were similar to those of human mature apo AI (fractional catabolic rate (FCR); 1.018 +/- 0.090/day vs. 0.976 1 0.031/day, respectively). In vivo conversion of rh-Met-proapo AI to mature apo AI was examined by autoradiography of the isoelectric focusing (IEF) slab gel, i.e., the HDL fraction from each sampling point was semiquantitatively applied to IEF. It was found that the radioactivity of rh-Met-proapo AI migrated to more acidic isoproteins, the conversion was complete within 24 h, and the FCR of rh-Met-proapo AI was 9.20 +/- 1.34/day. Although the plasma decay curves of both human pro (rh-Met-proapo AI) and mature apo AI were significantly steeper than those of rabbit mature apo AI4 and apo AI5 (FCR; 0.703 +/- 0.027/day and 0.795 +/- 0.031/day, respectively), the conversion rate of human rt-Met-proapo AI to mature apo AI in rabbit was assumed to be 1:1. In vitro incubation of rh-Met-proapo AI with rabbit serum produced mature apo AI isoproteins, as determined by the apo AI immunoblotting method. Prediction of the amino acid sequence at the NH2 terminus of rabbit proapo AI showed that the prosegment consisted of an alpha helix with a high probability of a beta turn at Pro9, which is close to that in humans. Thus, (1) the proteolytic cleavage of proapo AI is an extracellular event, (2) the converting enzyme in rabbits can also process human proapo AI, (3) this converting enzyme does not specifically and directly attack the Gln6-Asp7 bond which links the carboxyl-terminal residue of the hexapeptide to the amino-terminal residue of human mature apo AI. The conformation of proapo AI at the NH2 terminus (alpha helix of the prosegment and a beta turn at Pro9) may have a key role in this cleavage, and (4) the examination of rh-Met-proapo AI in rabbits helps to explain the early events of HDL biogenesis.

Amino Acid Sequence↗

PubMed1986

Isolation of a cDNA clone for chick intestinal apolipoprotein AI (Apo-AI) and its use for detecting apo-AI mRNA expression in several chick tissues.

Three cDNA clones for chick apolipoprotein AI (Apo-AI), the major protein component of plasma high-density lipoproteins, have been isolated. The identity of the clones has been established first by screening a cDNA library in the pEX1 expression vector with anti-Apo-AI antibodies, second by Western blot analysis of the proteins expressed by positive clones. The use of the clone containing the largest, presumably full-size, cDNA insert (apo5C12) in molecular hybridization experiments confirms that apo-AI mRNA is expressed mainly in chick small intestine and liver. Furthermore, we provide evidence that brain, heart and skeletal muscle also synthesize significant amounts of apo-AI mRNA. The Southern-blot hybridization pattern of the restriction-enzyme-digested chick DNA with the apo5C12 DNA is consistent with there being a single copy of the apo-AI gene.

Animals↗

PubMed2004

Fertility of holstein dairy heifers after synchronization of ovulation and timed AI or AI after removed tail chalk.

Nonlactating Holstein dairy heifers (n=352) 13 mo of age were managed using a 42-d artificial insemination (AI) breeding period in which they received AI after removed tail chalk evaluated once daily. At AI breeding period onset (d 0), heifers were randomly assigned to receive synchronization of ovulation (100 microg of GnRH, d 0; 25 mg of PGF2alpha, d 6; 100 microg of GnRH, d 8) and timed AI (TAI; d 8) and AI after removed tail chalk for the entire AI breeding period (GPG; n=175), or AI after removed tail chalk for the entire AI breeding period (TC; n=177). As expected, 17.7% (31/175) of GPG heifers received AI after removed tail chalk before scheduled TAI. Pregnancy rate per artificial insemination (PR/AI) at approximately 30 d after first AI tended to be greater for TC (46.5%) than for GPG (38.3%) heifers. No treatment x inseminator interaction was detected; however, overall PR/AI was low for heifers in both treatments due to variation among the 3 inseminators (24.8, 30.0, and 58.0%). Pregnancy loss from approximately 30 to approximately 75 d after first AI was 10% and did not differ between treatments. Based on survival analysis, days to first AI was greater for TC than for GPG heifers, whereas days to pregnancy across the 42-d AI breeding period did not differ between treatments. Overall, 81.2% of GPG heifers receiving TAI synchronized luteal regression and ovulated within 48 h after the second GnRH injection. We conclude that this synchronization protocol can yield acceptable fertility in dairy heifers if AI to estrus is conducted between treatment with GnRH and PGF2alpha and AI efficiency is optimized.

Animals↗

PubMed2026

Human-AI Interaction With AI-Assisted Tumor Overlays in Pediatric Whole-Body Magnetic Resonance Imaging: Exploratory Reader Study.

BACKGROUND: AI tools have the potential to enhance personalized clinical care, particularly in radiology. However, their integration into clinical workflows remains complex, especially in pediatric oncology, where early cancer detection is critical. Children with Li-Fraumeni syndrome (LFS), a rare cancer predisposition disorder, undergo regular surveillance whole-body magnetic resonance imaging (wbMRI), which presents an opportunity for AI-assisted tumor detection. OBJECTIVE: We evaluated the feasibility of an AI-assisted overlay for highlighting tumor-like regions in pediatric surveillance wbMRI and explored how access to the overlay influenced radiologist workflow, candidate-lesion marking behavior, follow-up recommendations, and perceived workload. METHODS: We developed a patch-based AI segmentation model trained on augmented 2D slices from 675 surveillance wbMRI volumes of pediatric patients with LFS. The model was designed to highlight regions with high tumor probability. A reader study was conducted with 2 radiologists who independently reviewed wbMRI cases both with and without AI assistance. We measured evaluation time, number and location of reader-marked candidate lesions, type of follow-up recommendation, and subjective feedback using structured questionnaires. RESULTS: AI assistance altered interpretation workflows for both radiologists, with mixed effects. On average, the time required to evaluate each case increased when using the AI tool for both radiologists. However, one radiologist had an increase in the number of candidate lesion locations selected with the tool, and one had a decrease in the number of candidate lesion locations selected with the tool. Subjective feedback indicated that one of the radiologists reported lower mental demand with the AI tool, while both radiologists reported lower stress with the AI tool. Interrater variability was evident, underscoring the need for personalized calibration of AI tools. CONCLUSIONS: AI-assisted wbMRI interpretation can improve tumor detection in pediatric cancer surveillance by reducing false negatives. However, its influence on workflow efficiency and interradiologist variability highlights the importance of careful implementation. Successful integration requires addressing challenges such as improving the predictive precision of AI models, offering intuitive end-user designs and instructions, and building trust in AI outputs. AI outputs can influence workflow and behavior in reader-specific ways. Clinical translation will require larger, randomized, multireader studies and model refinement to reduce false positives and quantify lesion-level reader performance. This can help ensure better patient outcomes in addition to reduced clinician burnout.

Humans↗

PubMed1993

Monoclonal antibodies to human apolipoprotein AI: probing the putative receptor binding domain of apolipoprotein AI.

We have used four monoclonal antibodies (MAbs) specific for human apolipoprotein (apo) AI, designated AI-1, AI-3, AI-4.1 and AI-4.2, to study the interaction between high-density lipoprotein HDL3 and rat liver plasma membranes. MAbs AI-1 and AI-3 recognize epitopes within residues 28-47 and 140-147 respectively of apoA-I [Allan, Tetaz and Fidge (1991) J. Lipid Res. 32, 595-601]. Two previously unreported MAbs, AI-4.1 and AI-4.2, were raised against purified CNBr fragment 4 (CF4) of apoAI, the C-terminal region. Using e.l.i.s.a. and immunoblotting techniques, we have demonstrated that all four MAbs recognize distinct epitopes within apoAI. Epitope mapping studies using endoproteinase cleavage peptides of CF4 showed that AI-4.1 binds to an epitope within residues 223-233, which is poorly exposed on apoAI molecules associated with lipid. Fab fragments derived from MAb AI-4.2 inhibited the binding of 125I-labelled HDL3 to rat liver plasma membranes, whereas Fab fragments from AI-4.1, AI-3 and AI-1 had little or no effect. In ligand blotting studies with purified CNBr fragments of apoAI and using apoAI-specific antibodies for detection, CF4 showed the highest capacity to recognize two HDL-binding proteins previously identified in rat liver plasma membranes. We propose that the specific interaction between HDL and liver plasma membranes is largely mediated through a binding domain in the C-terminus of apoAI, which is consistent with the involvement of specific receptors for the apolipoprotein moiety of HDL.

Animals↗

PubMed2003

Conception rates after AI in Swedish red and white dairy heifers: relationship with progesterone concentrations at AI.

Blood samples were collected from 211 dairy heifers at the time of field insemination [artificial insemination (AI)]. Heifers were defined as either first-service heifers (n = 91) or third to eigth-service heifers [presumed (third AI, n = 60)] or well-defined repeat breeders (greater than the fourth AI, n = 60). Plasma progesterone concentrations at AI were evaluated in relation to oestrous behaviour at AI and conception rates post-AI. Conception rates after third AI were good, but conception rates decreased markedly after fourth AI and onwards. Those heifers that did not become pregnant after AI had significantly higher basal progesterone concentrations (>0.5 nmol/l) at AI, so-called suprabasal concentrations, compared with those which conceived after AI (irrespective of the number of AI practised). Relative risk for repeat breeding was 58% after AI performed at suprabasal progesterone concentrations, while it was 42% at basal (0.5) progesterone concentrations. Results from this field study confirm results obtained in earlier controlled studies of repeat-breeder heifers (RBH), indicating that the current definition of repeat breeding should be retained. Analysis of suprabasal progesterone concentrations could be considered as a tool for identification of RBH, provided that heat detection and AI timing are optimal. Besides considering the direct costs involved in repeat breeding, it remains to be determined whether it would be economically beneficial to identify and exclude RBH from the breeding population.

Animals↗

PubMed1997

Subjects with ApoA-I(Lys107-->0) exhibit enhanced fractional catabolic rate of ApoA-I in Lp(AI) and ApoA-II in Lp(AI with AII).

Our purpose was to examine HDL metabolism in a Finnish kindred with a 3-bp deletion in the apolipoprotein (apo) A-I gene, resulting in a deletion of Lys107 in the mature apoA-I. Patients with this mutation [apoA-I(Lys107-->0)] have reduced plasma HDL cholesterol and lipoprotein (AI with AII) [Lp(AI w AII)] concentrations, but not Lp(AI) levels, compared with unaffected family members. Using primed constant infusions of [5,5,5-2H3]leucine, we determined the residence time (RT) and absolute production rate (APR) of apoA-I and apoA-II entering plasma in two subpopulations of HDL particles: [Lp(AI) and Lp(AI w AII)] in three patients heterozygous for apoA-I(Lys107-->0) and in seven healthy control subjects. In patients, the mean RT of apoA-I in Lp(AI) (3.75+/-1.68 days) was less than half that observed in control subjects (8.01+/-2.51 days, P<.05). The mean RT of apoA-I in Lp(AI w AII) was also lower in patients than in control subjects, but differences were not statistically significant (4.72+/-2.42 versus 6.50+/-2.19 days). The mean RT of apoA-II in Lp(AI w AII) was significantly lower in patients (5.24+/-1.65 days) than in control subjects (9.64+/-3.57 days, P<.05). The APR of apoA-I into Lp(AI) was twofold higher in patients (5.9+/-2.1 mg x kg(-1) x d(-1)) than in control subjects (2.5+/-0.9, P<.05). The APRs of apoA-I and apoA-II into Lp(AI w AII) were similar in patients and control subjects. Our results are consistent with the concept that patients heterozygous for the apoA-I(Lys107-->0) mutation have enhanced fractional catabolism of apoA-I and apoA-II in both HDL subspecies, especially in Lp(AI), and an increase in apoA-I production only into Lp(AI), which may be compensatory. Therefore, only their Lp(AI w AII) levels are decreased.

Adult↗

PubMed1998

Beneficial effect on serum apo AI, apo B and Lp AI levels of Ramadan fasting.

In order to investigate for the first time in Morocco the effect of fasting in Ramadan, the ninth lunar month of the muslim year, on lipoprotein metabolism, we determined the levels of serum apolipoproteins; apolipoprotein AI (apo AI), apo B, apo AIV and those of lipoprotein particles; apo AI-containing lipoprotein particles (Lp AI) and also apo AI and apo AII containing lipoprotein particles (Lp AI:AII) in a group of 32 healthy, volunteer adult males. Determination of all these parameters was carried out on each week of the month of Ramadan and the results are compared with the pre-fasting and the post-fasting values. Ramadan fasting reduces significantly serum apo B (P < 0.05), while serum apo AI is significantly increased (P < 0.05) compared with the pre-fasting period. The increase of apo AI occurred on day 29 of Ramadan by 11.8%. Serum apo AIV was unchanged during the fasting period indicating that food intake during Ramadan is not based on lipid diet. The observed diet pattern during Ramadan showed an increase of total energy intake based on carbohydrates (+1.4% of total energy), proteins (+0.4% of total energy) but not on fat (-0.7% of total energy), compared with a usual diet used in the rest of the year. The fat diet is high in monounsaturated (P < 0.05) and polyunsaturated fatty acid in contrast to saturated fatty acid which decreased (P < 0.05) during Ramadan. On the other hand, analysis of serum Lp AI and Lp AI:AII showed that the levels of Lp AI:AII were unchanged but those of Lp AI were significantly increased (P < 0.01) at the end of Ramadan. These findings show that feeding behaviour that occurs during Ramadan beneficially affects serum apolipoprotein metabolism and may contribute to prevention of cardiovascular diseases.

Adult↗

PubMed2000

Suppression of induced atherosclerosis in h-apo AI transgenic mice by overexpression of human apo AI in the aortic wall.

OBJECTIVES: To investigate the inhibitory effect of expressed human apolipoprotein AI (h-apo AI) and high density lipoprotein (HDL) on atherosclerosis development in transgenic mice, and cultivation of smooth muscle cells isolated from the aortic wall of transgenic mice that are able to produce human apo AI in vitro. METHODS: Both h-apo AI transgenic mice and normal C57 mice were fed with either a regular chow or a high-fat diet containing 5% pork lard, 1.25% cholesterol and 0.25% sodium cholate for 14 or 24 weeks respectively. Human apo AI mRNA were detected by Northern blot. Plasma apo AI levels were measured using a radio-immuno-diffusion assay, and plasma lipid levels were measured using a colorimetric assay. Image analysis was performed in order to quantify the fatty streak areas stained with oil red O. In addition, smooth muscle cells isolated from the media layer of the aortic wall of h-apo AI transgenic mice were cultured for the detection of human apo AI produced. RESULTS: Higher levels of h-apo AI mRNA were found in liver, small intestine, kidneys and aortae in transgenic mice than in the controls all on a high-fat diet. The transgenic mice had an increased level of serum apo AI and HDL-cholesterol and the fatty streak area counted at the aortic sinus was approximately 5-fold less in the transgenic mice after feeding with a high fat ration, particularly after 24 weeks. SMC isolated from the transgenic mice aortae were cultivated and able to express h-apo AI mRNA and its related protein. CONCLUSION: Elevation of h-apo AI and HDL in serum and aortic wall of the transgenic mice has a remarkably inhibitory effect on the development of experimental atherosclerosis.

Animals↗

PubMed2001

The LuxS-dependent autoinducer AI-2 controls the expression of an ABC transporter that functions in AI-2 uptake in Salmonella typhimurium.

In a process called quorum sensing, bacteria communicate with one another using secreted chemical signalling molecules termed autoinducers. A novel autoinducer called AI-2, originally discovered in the quorum-sensing bacterium Vibrio harveyi, is made by many species of Gram-negative and Gram-positive bacteria. In every case, production of AI-2 is dependent on the LuxS autoinducer synthase. The genes regulated by AI-2 in most of these luxS-containing species of bacteria are not known. Here, we describe the identification and characterization of AI-2-regulated genes in Salmonella typhimurium. We find that LuxS and AI-2 regulate the expression of a previously unidentified operon encoding an ATP binding cassette (ABC)-type transporter. We have named this operon the lsr (luxS regulated) operon. The Lsr transporter has homology to the ribose transporter of Escherichia coli and S. typhimurium. A gene encoding a DNA-binding protein that is located adjacent to the Lsr transporter structural operon is required to link AI-2 detection to operon expression. This gene, which we have named lsrR, encodes a protein that represses lsr operon expression in the absence of AI-2. Mutations in the lsr operon render S. typhimurium unable to eliminate AI-2 from the extracellular environment, suggesting that the role of the Lsr apparatus is to transport AI-2 into the cells. It is intriguing that an operon regulated by AI-2 encodes functions resembling the ribose transporter, given recent findings that AI-2 is derived from the ribosyl moiety of S-ribosylhomocysteine.

ATP-Binding Cassette Transporters↗

PubMed2004

An investigation of the mechanisms underlying the disparity between rate of residual endocervical adenocarcinoma in situ (AIS) in hysterectomy specimens and clinical failure rate following conservatively treated AIS.

The location, amount, and anatomic relationships of adenocarcinoma in situ (AIS) in 5 delayed second cone biopsy excision specimens and 21 definitive-therapy hysterectomy specimens were measured in relation to the neosquamocolumnar junction (nSCJ). All 5 biopsy specimens had 1 to 2 mm of AIS situated at the nSCJ. None had AIS in the proximal endocervix, despite positive or extremely close biopsy margins. Residual AIS in hysterectomy specimens was located proximal to the nSCJ in 19 (90%) of 21 cases. The mean distance between AIS and the nSCJ was 4.9 mm in 12 (86%) of 14 hysterectomy specimens. The mean maximum length of AIS was 4.6 mm in hysterectomy specimens and 1.1 mm in biopsy specimens. Some postbiopsy failures might be de novo neoplasms that begin at the nSCJ rather than recrudescence of persistent AIS. Small amounts of residual AIS following cone biopsy excision might be eradicated by the healing process. These 2 factors might underlie the disparate rates of residual AIS in hysterectomy specimens and postbiopsy excision failures and also explain the poor correlation between biopsy margin status and clinical failure. Factors that impact postbiopsy AIS eradication might be unrelated to de novo AIS beginning at the nSCJ.

Adenocarcinoma↗

PubMed1991

Cholesterol efflux from cells to immunopurified subfractions of human high density lipoprotein: LP-AI and LP-AI/AII.

Using immunoaffinity chromatography, we separated human high density lipoprotein (HDL) into two subfractions: LP-AI, in which all particles contain apolipoprotein A-I (apoA-I) but no apoA-II, and LP-AI/AII, in which all particles contain both apoA-I and apoA-II. To compare LP-AI and LP-AI/AII as acceptors of cell cholesterol, the isolated subfractions were diluted to 50 micrograms phospholipid/ml, and then incubated with monolayer cultures of cells in which whole-cell and lysosomal cholesterol has been labeled with 14C and 3H, respectively. We used three cell types (Fu5AH rat hepatoma cells, normal human skin fibroblasts, and rabbit aortic smooth muscle cells). When these cells were prepared to contain normal physiological quantities of cholesterol (20-35 micrograms/mg protein), LP-AI and LP-AI/AII were nearly equally efficient in promoting efflux of both whole-cell and lysosomal cholesterol. For whole-cell cholesterol, the rate constants for efflux to LP-AI and LP-AI/AII were: 0.050/h and 0.053/h, respectively, with Fu5AH cells; 0.0063/h and 0.0074/h with GM3468 human skin fibroblasts; and 0.0076/h and 0.0079/h with rabbit aortic smooth muscle cells. When cholesterol in hepatoma cells or fibroblasts was elevated two- to threefold above normal, there was still not difference in efflux of whole-cell cholesterol to LP-AI and LP-AI/AII. In longterm incubations, the net depletion of cholesterol mass from cholesterol-enriched cells was either identical with the two HDL subfractions, or somewhat greater with LP-AI/AII.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Polymorphism in the promoter region of the apolipoprotein AI gene associated with differences in apolipoprotein AI levels: the European Atherosclerosis Research Study.

The effect associated with the substitution of adenine (A) for guanidine (G) in the promoter region of the apolipoprotein AI gene (-75 bp) with plasma apo AI and high-density lipoprotein (HDL) levels was investigated in the European Atherosclerosis Research Study (EARS). This is a study of healthy offspring (cases) of fathers who had suffered premature myocardial infarction (MI) before age 55 years (n = 565) and age- and sex-matched controls (n = 1,078) from 12 European countries, divided into 5 regions based on geography and language. The frequency of the polymorphism was not significantly different among the regions and the relative frequency of the rare A allele was similar in cases and controls (0.159 vs. 0.142) combining data from all regions. Individuals with one or more A allele had significantly higher plasma apo AI levels (P < 0.05) than individuals homozygous for the G allele. This effect was consistent in all regions. The data were analyzed separately in males and females. In females, those with one or more A allele had significantly higher apo AI levels (P = 0.05) than individuals homozygous for the G allele, and this raising effect of the A allele was greater in cases than controls for both apo AI (5.23% vs. 1.56%) and HDL (4.48% vs. 1.89%). In males, the A allele was associated with higher levels of apo AI and HDL, but the effect was much smaller and the differences did not reach statistical significance. In the females, where the effect of the A allele was strongest, the effect on apo AI associated with genotype was evident in non-smokers, and individuals with one or two A alleles had 3.6% higher apo AI and 3.14% higher HDL levels than individuals homozygous for the G allele. However, in the female smokers the raising effect of the A allele was greatly reduced (0.56%). Thus genetic variation in the promoter region of the apo AI gene is associated with differences in apo AI and HDL levels in healthy individuals throughout Europe, but the effect is modulated by gender, environmental factors such as smoking, and a family history of MI.

Adenine↗

PubMed2004

Comparison of timed AI after synchronized ovulation to AI at estrus: reproductive and economic considerations.

A timed artificial insemination (TAI) protocol using OvSynch was compared to artificial insemination (AI) at detected estrus in 2 large dairy herds differing in reproductive management. Cows were synchronized for TAI starting at 62 and 42 d in milk in herds 1 and 2, respectively. The OvSynch regimen included: GnRH (buserelin) at 0.02 mg (i.m.) on d 0; PGF2alpha (tiaprost) at 0.75 mg (i.m.) on d 7; buserelin at 0.02 mg (i.m.) on d 9; and TAI 16 to 20 h later. After TAI, cows seen in estrus received AI, whereas cows diagnosed not pregnant were resynchronized for TAI. Control cows received AI based on detected estrus after voluntary waiting periods of 72 d in herd 1 and 50 d in herd 2. An economic analysis included costs associated with days open, culling, AI, synchrony products, treatment, and examinations. A sensitivity analysis of those variables determined effects on total costs per pregnancy. Use of OvSynch reduced intervals to first AI and days open in both herds and reduced culling for infertility in herd 2. Conception rates for first AI at detected estrus were significantly higher compared to TAI in both herds and for overall AI at estrus in herd 2. For groups assigned to AI at estrus, mean 21-d submission rates over 200 d for AI were higher in herd 1 than in herd 2 (55.6 vs. 28.6%). Days open and culling were the major cost factors. Although OvSynch improved reproduction in both herds, AI based on detected estrus was economically superior in herd 1, whereas OvSynch was superior in herd 2. This was consistent across ranges of cost factors evaluated. Evaluation of synchrony protocols should include reproductive performance along with appropriate costs associated with treatments. Such costs may offset benefits to reproduction in herds with good estrous detection rates.

Animals↗

PubMed1993

Role of genetic variation at the apo AI-CIII-AIV gene cluster in determining plasma apo AI levels in boys and girls.

We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (-75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8-11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II-CIII) and the apo CIII-AIV intergenic region (Pvu II-AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V-V+ of the G/A substitution and the PvuII-AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V-V-. In girls, however, there was evidence of significant interaction of effects between the PvuII-AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V+) of the PvuII-AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII-CIII and PvuII-AIV polymorphisms.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenine Nucleotides↗

PubMed1999

Is traumatic axonal injury (AI) associated with an early microglial activation? Application of a double-labeling technique for simultaneous detection of microglia and AI.

The aim of the present study was to determine whether axonal injury (AI) induces a microglial reaction within 15 days after brain trauma. In 40 selected cases of confirmed AI, the topographical relation of AI and microglial reaction was assessed using an immunohistochemical double-labeling technique for simultaneous demonstration of AI using beta-amyloid precursor protein (beta-APP) antibody and of microglia using CD68 antibody. Although traumatic injury was usually followed by a moderate early diffuse rise in the number of CD68-reactive cells in the white matter, increases in macrophages in areas of AI accumulation were only sporadic and did not occur until after 4 days. At survival intervals of 5-15 days a moderate microglial reaction in regions of beta-APP-positive injured axons was detected, at maximum, in half of the case material. During this interval AI-associated satellitosis-like clusters or stars described by other authors after a survival time of more than 7 weeks were an isolated phenomenon. The prolonged microglial reaction as well as the reduction of beta-APP-positive AI during longer survival periods supports the hypothesis that AI is not primarily chemotactically attractive and that the damage to a portion of beta-APPstained axons may be partly reversible. Most cases clearly require a prolonged interval of more than 15 days before initiation of the final scavenger reaction. For forensic purposes the increase in the number of microglial cells within the region of AI accumulation after a survival time of more than 5 days and the multiple and distinct demonstration of star-like microglial reactions within the white matter after survival times exceeding 7 weeks may provide valuable postmortem information on the timing of a traumatic event.

Adolescent↗

PubMed2006

Scoring of anatomic injury after trauma: AIS 98 versus AIS 90--do the changes affect overall severity assessment?

BACKGROUND: Although several changes were implemented in the 1998 update of the abbreviated injury scale (AIS 98) versus the previous AIS 90, both are still used worldwide for coding of anatomic injury in trauma. This could possibly invalidate comparisons between systems using different AIS versions. Our aim was to evaluate whether the use of different coding dictionaries affected estimation of Injury Severity Score (ISS), New Injury Severity Score (NISS) and probability of survival (Ps) according to TRISS in a hospital-based trauma registry. MATERIALS AND METHODS: In a prospective study including 1654 patients from Ulleval University Hospital, a Norwegian trauma referral centre, patients were coded according to both AIS 98 and AIS 90. Agreement between the classifications of ISS, NISS and Ps according to TRISS methodology was estimated using intraclass correlation coefficients (ICC) with 95% CI. RESULTS: ISS changed for 378 of 1654 patients analysed (22.9%). One hundred and forty seven (8.9%) were coded differently due to different injury descriptions and 369 patients (22.3%) had a change in ISS value in one or more regions due to the different scoring algorithm for skin injuries introduced in AIS 98. This gave a minimal change in mean ISS (14.74 versus 14.54). An ICC value of 0.997 (95% CI 0.9968-0.9974) for ISS indicates excellent agreement between the scoring systems. There were no significant changes in NISS and Ps. CONCLUSIONS: There was excellent agreement for the overall population between ISS, NISS and Ps values obtained using AIS 90 and AIS 98 for injury coding. Injury descriptions for hypothermia were re-introduced in the recently published AIS 2005. We support this change as coding differences due to hypothermia were encountered in 4.3% of patients in the present study.

Abbreviated Injury Scale↗

PubMedDate not supplied

Pig apolipoprotein AI self-association and interaction with L-alpha-dimyristoylphosphatidylcholine as compared with human apolipoprotein AI.

Associative properties of apolipoprotein AI of HDL were compared in the pig and human. Self-association of apo AI (determined by dimethylsuberimidate cross-linking) occurred preferentially as tetramers in pig AI as compared to equal proportions of tetra and pentamers in human. Like human apo AI, the pig apoprotein is susceptible of recombining with increasing concentrations of phospholipids (dimyristoylphosphatidylcholine). Both apoproteins first give rise to particles containing 2 AI molecules (DMPC : AI molar ratio of 20 - 200) then to larger particles containing 3 apoprotein molecules (DMPC : AI molar ratio of 200 - 600). Despite these similarities in phospholipid association, pig apolipoprotein displayed less affinity for the lipid vesicles and should, therefore, be more readily exchangeable. Upon incubation with human HDL, however, pig apo AI displaces human apo AI, but it does not associate with it in mixed particles, and forms heavy particles from which the human apoprotein has been totally displaced. Protein-protein associations at the surface of lipoproteins therefore exhibit definite species specificity.

Acetylation↗