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Intravenous hydrophobic drug delivery: a porous particle formulation of paclitaxel (AI-850).

PURPOSE: To develop a rapidly dissolving porous particle formulation of paclitaxel without Cremophor EL that is appropriate for quick intravenous administration. METHODS: A rapidly dissolving porous particle formulation of paclitaxel (AI-850) was created using spray drying. AI-850 was compared to Taxol following intravenous administration in a rat pharmacokinetic study, a rat tissue distribution study, and a human xenograft mammary tumor (MDA-MB-435) model in nude mice. RESULTS: The volume of distribution and clearance for paclitaxel following intravenous bolus administration of AI-850 were 7-fold and 4-fold greater, respectively, than following intravenous bolus administration of Taxol. There were no significant differences between AI-850 and Taxol in tissue concentrations and tissue area under the curve (AUC) for the tissues examined. Nude mice implanted with mammary tumors showed improved tolerance of AI-850, enabling higher administrable does of paclitaxel, which resulted in improved efficacy as compared to Taxol administered at its maximum tolerated dose (MTD). CONCLUSIONS: The pharmacokinetic data indicate that paclitaxel in AI-850 has more rapid partitioning from the bloodstream into the tissue compartments than paclitaxel in Taxol. AI-850, administered as an intravenous injection, has been shown to have improved tolerance in rats and mice and improved efficacy in a tumor model in mice when compared to Taxol.

Animals↗

A simplified and efficient procedure for the purification of apolipoprotein AI from human serum high-density lipoprotein-3 by preparative isoelectric focussing on polyacrylamide gel beads.

An improved method is described for the purification of milligram amounts of apolipoprotein AI from serum apo-HDL3 by isoelectric focussing on polyacrylamide gel beads. The procedure involves a single focussing over a narrow (1.3 unit) pH gradient, and permits isolation of apo-AI of exceptional purity and in high yield (75% recovery of HDL3 protein, ca. 50% corresponding to pure apo-AI). The electrophoretic mobility, pI values, molecular weight, antigenicity and amino acid composition of such apo-AI were indistinguishable from those reported in the literature. A rabbit antiserum to apo-AI isolated by focussing exhibited similar immunological reactivity to one prepared from an antigen isolated by gel filtration chromatography; moreover, apo-AI purified by the respective procedures reacted identically with both antisera. We conclude that isoelectric focussing on a support of polyacrylamide gel beads (as Bio-Gel P60) presents certain advantages for the isolation of highly purified apo-AI over both conventional chromatographic procedures and isoelectric focussing on a Sephadex support.

Acrylic Resins↗

How AI-supported intelligent systems support infection prevention and control training in healthcare: A systematic review of educational functions and outcomes.

AIMS: Artificial intelligence (AI)-supported intelligent systems have been increasingly incorporated into infection prevention and control (IPC) education and training, primarily to support the monitoring of observable behaviors and the provision of feedback. However, existing evidence has focused largely on short-term compliance outcomes, with limited synthesis of the educational role of AI-supported intelligent systems in supporting sustained IPC competence. This systematic review examined how AI-supported intelligent systems have been designed and used to support IPC education and training, with a focus on system characteristics, educational functions, and reported outcomes. DESIGN: A systematic literature search was conducted across the PubMed/MEDLINE, Embase, Cochrane, and CINAHL databases. DATA SOURCES: A total of 18 studies met the inclusion criteria. Findings were qualitatively synthesized according to system design characteristics, educational functions, and outcome domains. REVIEW METHODS: Methodological quality was appraised using the Mixed Methods Appraisal Tool. RESULTS: Most AI-supported intelligent systems focused on hand hygiene and relied on fully automated monitoring systems to capture behaviors and provide performance feedback. Educational functions were predominantly limited to performance assessment, automated feedback, and reminders. Outcomes were mainly measured using compliance or performance metrics, whereas sustained behavioral change and decision quality were rarely assessed. CONCLUSIONS: AI-supported intelligent systems have been used primarily to reinforce short-term IPC performance and compliance. However, their current applications for supporting sustained competence over time remain limited. The findings of this review suggest that AI-supported intelligent systems may serve as maintenance-oriented educational support by extending learning beyond initial instruction through repeated practice and feedback. Future research should prioritize outcome measures that capture the durability of performance and decision-making processes to better align AI-supported intelligent systems used in IPC education and training with the educational demands of clinical practice.

Humans↗

Embryonic mortality in buffaloes synchronized and mated by AI during the seasonal decline in reproductive function.

The aim was to determine the factors that contribute to embryonic mortality in buffaloes mated by AI during a period of increasing day length which corresponds to a natural decline in reproductive activity. Italian Mediterranean buffalo cows (n=243) showing regular estrous cycles were synchronized using the Ovsynch-TAI program and mated by AI at 16 and 40 h after the second injection of GnRH. Blood samples were collected on Days 10 and 20 after the first AI and assayed for progesterone (P4). Pregnancy diagnosis was undertaken on Days 26 and 40 after the first AI using rectal ultrasonography. Buffaloes with a conceptus on Day 26 but not on Day 40 were judged to have undergone embryonic mortality and for these animals uterine fluid was recovered by flushing and analysed for common infectious agents. Estrus synchronization was achieved in 86% of buffaloes and the pregnancy rate on Day 40 was 34%. Embryonic mortality between Days 26 and 40 occurred in 45% of buffaloes and was associated with the presence of significant infectious agents in only 10 buffaloes (8%). Concentrations of P4 on Day 10 after AI were higher (P<0.05) in buffaloes that established a pregnancy than in buffaloes that showed embryonic mortality that was not associated with infectious agents. Similarly, on Day 20 after AI P4 concentrations were higher (P<0.01) in pregnant buffaloes compared with non-pregnant buffaloes and buffaloes that had embryonic mortality. It is concluded that a reduced capacity for P4 secretion can explain around 50% of embryonic mortalities in buffaloes synchronised and mated by AI during a period of low reproductive activity and that other as yet unidentified factors also have a significant effect on embryonic survival.

Animals↗

The effects of GnRH treatment at the time of AI and 12 days later on reproductive performance of high producing dairy cows during the warm season in northeastern Spain.

It was hypothesized that gonadotropin-releasing hormone (GnRH) treatment at the time of insemination and 12 days later increases conception rates. The aim of the present study was to evaluate the effects of GnRH treatment at the time of insemination or at the time of insemination and 12 days later on reproductive performance during the warm season in high producing dairy cows. The effect of GnRH treatment on the incidence of subsequent twin pregnancies and pregnancy losses was also evaluated. Data were analyzed using logistic regression methods. Of the entire series of 1289 AI, 373 (29%) resulted in pregnancy. Three study groups were established to evaluate the effects of treatment on the conception rate: control (untreated cows, n=431), GnRH-0 (cows receiving GnRH at AI, n=429) or GnRH-0+12 (cows receiving GnRH at AI and at AI+12 days, n=429). Conception rates were 20.6% (89/431), 30.8% (132/429) and 35.4% (152/429) for animals receiving no treatment, GnRH at AI, and GnRH at AI and 12 days later, respectively. Based on the odds ratio, the probability of pregnancy was 0.80 and 0.46 times less likely for cows receiving treatment GnRH-0 and no treatment, respectively, than for cows receiving treatment GnRH-0+12 (reference). Of the 373 pregnant animals, 326 (87.4%) bore singletons and 47 (12.6%) carried twins. The effects of treatment on the dependent variables: twin pregnancy, additional corpus luteum and pregnancy loss were analyzed. Pregnancy loss between 38 and 90 days after insemination was registered in 30 (8%) cows: 17 (5.2%) in single and 13 (27.7%) in twin pregnancies. Fifty-six (15%) cows had an additional corpus luteum. No pregnancy losses were recorded in these cows. Treatment had no effect on the twin pregnancy rate. The treatment GnRH at AI and 12 days later increased the chances of an additional corpus luteum by a factor 3.7 (using the control group as reference). In conclusion, our results support the hypothesis that GnRH treatment at the time of insemination and 12 days later increases the conception rate in high producing dairy cows during the warm season. Although lower than double treatment, strong benefits were also registered following a single GnRH treatment at insemination. Under these conditions, treatment fails to affect the twin pregnancy rate yet increases the incidence of an additional corpus luteum in pregnant cows.

Abortion, Veterinary↗

Apolipoprotein AI and HDL(3) inhibit spreading of primary human monocytes through a mechanism that involves cholesterol depletion and regulation of CDC42.

The objective of the current study was to characterize the influence of high density lipoproteins (HDL) on processes related to the vascular recruitment of human monocytes, which may contribute to the anti-atherogenic properties of these lipoproteins. We show that HDL(3) and apo AI inhibit the following processes in primary human monocytes: (1) M-CSF induced cell spreading; (2) M-CSF stimulated expression of surface molecules involved in adhesion, migration, and scavenging; (3) fMLP induced chemotaxis. These processes are obviously modulated by the regulation of cellular cholesterol pools as indicated by the following findings. In Tangier monocytes with defective apo AI induced cholesterol efflux, apo AI had no influence on the spreading response. In control cells, stimulation of cholesterol efflux by p-cyclodextrin mimicked the effect of apo AI and HDL(3) on spreading and chemotaxis, whereas cholesterol loading with enzymatically modified LDL (E-LDL) showed the opposite effect. Finally, a similar inverse regulation by E-LDL and apo AI/HDL(3) was also observed in regard to the surface expression of beta(1)- and beta(2)-integrins as well as the hemoglobin/haptoglobin scavenger receptor CD163 and the Fcgamma-IIIaR CD16. CDC42 was identified as a potential downstream target linking changes in cellular cholesterol content to monocyte spreading and chemotaxis. Thus, CDC42 antisense markedly reduced spreading and, in parallel with their influence on monocyte spreading, HDL(3), apo AI and p-cyclodextrin down-regulated CDC42 expression while E-LDL had the inverse effect. The apo AI induced decrease of CDC42 protein expression was paralleled by the reduction of active GTP-bound CDC42. In summary, we provide evidence that HDL(3) and apo AI are able to inhibit processes in primary human monocytes, which are related to the recruitment of monocytes into the vessel wall and probably involve regulation of cellular cholesterol pools and CDC42 function.

Apolipoprotein A-I↗

Reproductive performance of lactating dairy cows treated with cloprostenol, hcg and estradiol benzoate for synchronization of estrus followed by timed AI.

In previous studies, we demonstrated that the administration of a luteolytic dose of cloprostenol, followed by 750 IU hCG plus 3 mg estradiol benzoate (EB) 12 h later, synchronized estrus in cows in the luteal phase. Most cows were ready for service 48 h after the beginning of treatment. The objectives of this study were to evaluate the reproductive performance of lactating dairy cows treated with this method of estrus synchronization and to determine the effect of decreasing the hCG-EB dose on synchronization and pregnancy rates after timed AI. Data were obtained from cows first inseminated within an interval of 45 to 70 d postpartum. A total of 2,472 lactating dairy cows in their first to second lactation period were assigned to 4 groups. Cows estimated to be in the luteal phase by rectal palpation were treated with 500 mcg, im, of cloprostenol and assigned to 1 of 3 groups to be intramuscularly injected with hCG-EB 12 h later at the following doses: Group 1 (n=626), 250 IU of hCG and 1 mg of EB; Group 2 (n=592), 500 IU of hCG and 2 mg of EB; and Group 3 (n=664), 750 IU of hCG and 3 mg of EB. Cows displaying natural estrus were inseminated to serve as controls (n=590). The synchronized cows were inseminated 48 h after cloprostenol injection, and control animals visually determined to be in natural estrus during the morning or afternoon were inseminated the following morning. Pregnancy diagnosis was performed by rectal palpation at 34 to 40 d postinsemination. All synchronized cows showed estrous activity within 24 to 36 h after cloprostenol treatment and were considered to be ready for service 48 h after this treatment. There was a significant effect of treatment on the pregnancy rate, either to first AI or to 2 rounds of AI. The pregnancy rate in response to first or second rounds of AI was similar to control rates for cows in Groups 1 and 2, and lower than control rates in Group 3. Cows in Group 1 showed a higher pregnancy rate to first AI than those in Group 3 (P<0.0001), and a higher pregnancy rate to second AI rounds than cows in Groups 2 (P<0.02) and 3 (P<0.0001). The number of cows returning to estrus was unaffected by treatment. However, treatment significantly decreased (P<0.01) the time of return to estrus as the hCG-EB dose increased. These findings indicate that the lowest dose of hCG-EB treatment tested gave the overall best pregnancy results among the treated groups. Furthermore, the synchronization protocol used in this experiment allows effective AI management of lactating dairy cows without the need for estrus detection.

Animals↗

The role of apoproteins AI and AII in binding of high-density lipoprotein3 to membranes derived from bovine aortic endothelial cells.

Although binding of high-density lipoproteins (HDL) to a variety of cells in culture has been widely reported, the mechanism of this binding has yet to be fully elucidated. The aim of the current studies was to explore the roles of apoproteins (apo) AI and AII in HDL3 binding to membranes derived from bovine aortic endothelial cells. Binding studies showed that HDL3 (which contains both apo AI and apo AII) and AII-HDL3 (which contain only apo AII) bound to membranes with similar affinity (44 +/- 6 and 41 +/- 9 micrograms/ml respectively) and capacity (673 +/- 97 and 969 +/- 101 ng bound/mg of membrane protein respectively). In contrast with these results, HDL3 [AI w/o AII] (which contain apo AI, but not apo AII) bound to the membranes with a significantly higher capacity (2228 +/- 206 ng bound/mg of membrane protein) and lower affinity (65 +/- 3 micrograms/ml) as compared with HDL3 or AII-HDL3. Therefore, although both apo AI and apo AII appear capable of facilitating HDL3 binding, the mechanisms involved probably differ. A model which fits the data postulates that a common receptor exists which binds both apo AI and apo AII, and that a particle containing AII can occupy up to four receptors (partly owing to each AII molecule containing two binding domains), whereas an HDL3 [AI w/o AII] particle can occupy only one.

Animals↗

Reciprocal changes of plasma apo AI and apo E levels in streptozotocin-induced diabetic rats.

Amounts of plasma lipids, apolipoprotein AI (apo AI) and apolipoprotein E (apo E) were measured in streptozotocin-induced diabetic rats. Plasma triglyceride and cholesterol levels of diabetic rats were not significantly different from those of control rats. Plasma apo AI levels of diabetic rats were significantly higher than those of control rats (78.2 +/- 29.3 vs 27.2 +/- 3.4 mg/dl, P less than 0.001), while plasma apo E levels of diabetic rats were significantly lower than those of control rats (4.2 +/- 1.0 vs 13.9 +/- 5.3 mg/dl, P less than 0.001). Insulin treatment (12U/day) of diabetic rats decreased plasma apo AI levels significantly (treated: 32.8 +/- 3.4, untreated: 48.7 +/- 6.2, control: 28.5 +/- 2.4 mg/dl) and normalized plasma apo E levels (treated: 16.1 +/- 1.7, untreated: 5.4 +/- 0.7, control: 15.8 +/- 1.3). Insulin injection (4U/day) to normal rats did not cause any changes in both plasma apo AI and apo E levels. The data indicate that diabetes is not always accompanied by hyperlipidemia, however this inevitably carries apoprotein abnormalities characterized by the high plasma apo AI and low apo E levels, which are reversible with insulin treatment. The changes in the levels of plasma apo AI and apo E could be related to the development of atherosclerosis in diabetes.

Animals↗

Metabolic and cardiorespiratory responses to the performance of Wing Chun and T'ai Chi Chuan exercise.

The primary purpose of this study was to examine the metabolic and cardiorespiratory responses to the continuous performance of Wing Chun and T'ai Chi Chuan exercise. No significant differences in VO2max or HRmax obtained during treadmill exercise were found between the practitioners of the two styles. Average values for oxygen uptake (VO2) were 23.3 +/- 7.5 ml.kg-1.min-1 (6.6 METS) and 16.0 +/- 3.9 ml.kg-1.min-1 (4.6 METS) for Wing Chun and T'ai Chi Chuan exercise, respectively. Mean heart rates obtained during exercise were 137 +/- 25 beats.min-1 for Wing Chun and 116 +/- 22 beats.min-1 for T'ai Chi Chuan exercise. These exercise values corresponded to 52.4% of VO2max and 70.5% of HRmax for Wing Chun and only 36.4% of VO2max and 59.8% of HRmax for T'ai Chi Chuan exercise. Thus, only the continuous performance of Wing Chun exercise elicited VO2 and HR responses that would be expected to bring about a cardiorespiratory training effect in subjects with a relatively low initial VO2max. The ventilatory equivalent for oxygen (VE/VO2) obtained during T'ai Chi Chuan exercise (21.7) was significantly lower than for Wing Chun exercise (24.2), suggesting that T'ai Chi practitioners utilize efficient breathing patterns during exercise. Both Wing Chun and T'ai Chi Chuan styles may have a small static component that produces a slightly elevated heart rate relative to metabolic load when compared to traditional aerobic activities. However, the effect was not severe and these forms of exercise should not be considered dangerous for individuals at high risk for cardiovascular disease.

Adult↗

Different AIS triplets: Different mortality predictions in identical ISS and NISS.

BACKGROUND: Previous studies demonstrated different mortality predictions for identical Injury Severity Scores (ISS) from different Abbreviated Injury Scale (AIS) triplets. This study elaborates in both scope and volume producing results of a larger magnitude, applicable to specific injury subgroups of blunt or penetrating, traumatic brain injury, various age groups, and replicated on NISS. METHODS: All patients hospitalized after trauma at 10 hospitals, with ISS/NISS (new ISS) generated by two AIS triplets, excluding patients with isolated minor or moderate injuries to a single body region were studied. Patients were separated into two groups based on the different triplets. Inpatient-mortality rates were calculated for each triplet group. Odds ratios were calculated to estimate the risk of dying in one triplet group as compared with the other. The chi test determined whether the difference in mortality rate between the two groups was significantly different. Differences were further explored for various subgroups. RESULTS: There were 35,827 patients who had ISS/NISS scores generated by two different AIS triplets. Significant differences in death rates were noted between triplet groups forming identical ISS/NISS. Odds ratio for being in the second group (always containing the higher AIS score) ranged from 2.3 to 7.4. CONCLUSIONS: ISS and NISS that are formed by different AIS triplets have significantly different inpatient-mortality rates. The triplet with the higher AIS score has higher inpatient-mortality rates, overall and in several sub-populations of varying vulnerability. The comparison of populations and the interpretation of ISS/NISS based outcome data should take this important information into account and the components of AIS triplets creating each ISS and NISS should be reported.

Abbreviated Injury Scale↗

Apolipoprotein AI is a serum and tissue marker of liver fibrosis in alcoholic patients.

The aim of this study was to assess the specific correlation of apolipoprotein-AI to hepatic fibrosis in alcoholic patients. Four hundred eighty two patients were prospectively included with serum measurement of apolipoprotein-AI within 10 days before liver biopsy. Pathologic features were semiquantitatively assessed by two observers. In 28 patients liver biopsy was used for histomorphometric assessment of fibrosis and immunohistochemical labeling of apolipoprotein-AI. Serum apolipoprotein-AI was negatively correlated to semiquantitative score of fibrosis (r = -0.50; p less than 0.001), independently of the scores of steatosis and alcoholic hepatitis (r = -0.44; p less than 0.001) and of the value of serum albumin, bilirubin, and prothrombin time (r = -0.22; p less than 0.001) and independently of the nutritional parameters (r = -0.29; p less than 0.009). The mean value of apolipoprotein-AI decreased according to the grade of fibrosis from 220 +/- 6 mg/dl (mean +/- SEM) to 110 +/- 8 mg/dl. Serum apolipoprotein-AI was negatively correlated to the percentage of fibrosis (r = -0.70; p less than 0.001) in the biopsies morphometrically assessed. The labeling was superimposed to the extracellular matrix. In conclusion, this study shows that decrease of apolipoprotein-AI is a serum and tissue marker of liver fibrosis independently of steatosis, alcoholic hepatitis, liver function tests, and nutritional parameters.

Apolipoprotein A-I↗

Contribution of polymorphisms in the apolipoprotein AI-CIII-AIV cluster to hyperlipidaemia in patients with gout.

BACKGROUND: Studies have shown that hyperuricaemia is independently related to the insulin resistance syndrome and that polymorphisms of the apolipoprotein AI-CIII-AIV cluster are also related to insulin resistance. OBJECTIVE: To study the prevalence of polymorphisms of the apolipoprotein AI-CIII-AIV cluster in persons with gout and to determine whether these polymorphisms contribute to the pathophysiology of gout or to altered lipid concentrations. METHODS: Plasma cholesterol, triglycerides, uric acid, VLDL, LDL, IDL, and HDL triglycerides, cholesterol, and the renal excretion of uric acid were measured in 68 patients with gout with gout and 165 healthy subjects. Polymorphisms were studied by amplification and RFLP in all subjects, using XmnI and MspI in the apolipoprotein AI gene and SstI in the apolipoprotein CIII gene. RESULTS: The A allele at position -75 bp in the apolipoprotein AI gene was more common in patients with gout than in controls (p = 0.01). Levels of cholesterol, triglycerides, uric acid, basal glycaemia, and HDL cholesterol were higher in the patients (p<0.001). In the patients there was also an interaction between mutations at the two polymorphic loci studied in the apolipoprotein AI gene (p = 0.04). An absence of the mutation at position -75 bp of the apolipoprotein AI gene resulted in increased plasma triglyceride levels. CONCLUSIONS: Gouty patients have an altered allelic distribution in the apolipoprotein AI-CIII-AIV cluster, which could lead to changes in levels of lipoproteins. This is not caused by a single mutation but rather by a combination of different mutations.

Adult↗

Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice.

Apolipoprotein E (apo E)-deficient mice are severely hypercholesterolemic and develop advanced atheromas independent of diet. The C57BL/6 strain differs from most inbred strains by having lower HDL concentrations and a high risk of developing early atherosclerotic lesions when fed an atherogenic diet. The relative HDL deficiency and atherosclerosis susceptibility of the C57BL/6 strain are corrected with the expression of a human apolipoprotein AI (apo AI) transgene in this genetic background. To examine if increases in apo AI and HDL are also effective in minimizing apo E deficiency--induced atherosclerosis, we introduced the human apo AI transgene into the hypercholesterolemic apo E knockout background. Similar elevations of total plasma cholesterol occurred in both the apo E knockout and apo E knockout mice also expressing the human apo AI transgene. The latter animals, however, also showed a two- to threefold increase in HDL and a sixfold decrease in susceptibility to atherosclerosis. This study demonstrates that elevating the concentration of apo AI reduces atherosclerosis in apo E deficient-mice and suggests that elevation of apo AI and HDL may prove to be a useful approach for treating unrelated causes of heightened atherosclerosis susceptibility.

Animals↗

Cholesterol efflux potential of sera from mice expressing human cholesteryl ester transfer protein and/or human apolipoprotein AI.

The ability of whole serum to promote cell cholesterol efflux and the relationships between apoprotein and lipoprotein components of human serum efflux have been investigated previously (de la Llera Moya, M., V. Atger, J.L. Paul, N. Fournier, N. Moatti, P. Giral, K.E. Friday, and G.H. Rothblat. 1994. Arterioscler. Thromb. 14:1056-1065). We have now used this experimental system to study the selective effects of two human lipoprotein-related proteins, apoprotein AI (apo AI) and cholesteryl ester transfer protein (CETP) on cell cholesterol efflux, when these proteins are expressed in transgenic mice. The percent efflux values for cholesterol released in 4 h from Fu5AH donor cells to 5% sera from the different groups of mice were in the order: background = human apo AI transgenic (HuAITg) > human CETP transgenic (HuCETPTg) > human apo AI and CETP transgenic (HuAICETPTg) >> apo AI knockout mice. In each group of mice a strong, positive correlation (r2 ranging from 0.64 to 0.76) was found between efflux and HDL cholesterol concentrations. The slopes of these regression lines differed between groups of mice, indicating that the cholesterol acceptor efficiencies of the sera differed among groups. These differences in relative efficiencies can explain why cholesterol efflux was not proportional to the different HDL levels in the various groups of mice. We can conclude that: (a) HDL particles from HuAITg mice are less efficient as cholesterol acceptors than HDL from the background mice; (b) despite a lower average efflux due to lower HDL cholesterol concentrations, HDL particles are more efficient in the HuCETPTg mice than in the background mice; and (c) the coexpression of both human apo AI and CETP improves the efficiency of HDL particles in the HuAICETPTg mice when compared with the HuAITg mice. We also demonstrated that the esterification of the free cholesterol released from the cells by lecithin cholesterol acyltransferase in the serum was reduced in the HuAITg and AI knockout mice, whereas it was not different from background values in the two groups of mice expressing human CETP.

Animals↗

Circulating antibodies to p40(AIS) in the sera of respiratory tract cancer patients.

Studies of immune recognition in cancer have defined several tumor antigens using autologous cytotoxic T lymphocytes and by detection of serum antibodies to tumor-associated products such as p53 and HER-2/neu. The AIS gene is a p53 homologue with multiple protein products (p40, p51, p63, p73L) on chromosomal arm 3q, frequently amplified and over-expressed in squamous-cell carcinoma of the respiratory tract. We analyzed the humoral response to p40(AIS) (a core domain of AIS products without the transactivation domain) by Western blot and ELISA using bacterially synthesized p40(AIS) protein. Antibodies were detected in the sera of 17/94 (18%) HNSCCs and 13/76 (17%) lung cancers, including 5/18 (26%) squamous-cell carcinomas. Anti-p40(AIS) antibodies were not associated with factors such as sex, age, histopathological grading, extent or size of primary tumor, lymph node involvement and staging. Our results indicate that amplification and over-expression of p40(AIS) may lead to antigen recognition by an autologous host with cancer. AIS may thus represent a new group of developmentally regulated genes that are recognized as tumor antigens.

Aged↗

[HDL-cholesterol or apolipoprotein AI: which parameter to choose?].

The French Consensus for cholesterol, established by ARCOL in 1989, recommends the use of HDL-cholesterol and apolipoprotein AI as additional parameters. The present study was undertaken to establish the correlation between these two parameters and to determine the limit value for apolipoprotein AI, based on the recommended limit of 0.90 mmol/L for HDL-cholesterol established by ARCOL. The correlation between HDL-cholesterol analysed by precipitation, and apolipoprotein AI analysed by immunonephelemetry on the day of blood drawing, determined on 1980 samples, raised a r value of 0.89. Using the regression line equation (y = 0.602 x + 0.629), the apolipoprotein AI value corresponding to the recommended HDL-cholesterol limit (0.90 mmol/L) was found to be 1.17 g/L, while the limit value established by ARCOL was 1.20 g/L. Using the HDL-cholesterol value of 0.90 mmol/L, the population was divided into a high risk group and a low risk group. With the limit value of 1.20 g/L for apolipoprotein AI, 89.2% of the subjects would be correctly classified. This percentage would be raised to 90.65% using the value (1.17 g/L) established in our study. Our conclusion is that apolipoprotein AI as well as HDL-cholesterol represent good markers for atherosclerosis in the clinical practice. The advantage of HDL-cholesterol is that the determination of this parameter allows the calculation of LDL-cholesterol which is used in all consensus, while the advantage of apolipoprotein AI is that it may be analysed automatically.

Apolipoprotein A-I↗

The topographic organization of corticocollicular projections from physiologically identified loci in the AI, AII, and anterior auditory cortical fields of the cat.

The connections of the three auditory fields AI, AII, and the anterior auditory field (AAF) with the inferior colliculus (IC) were studied using anterograde tracing techniques. Microinjections of tracers were placed at physiologically identified loci after these fields had been functionally mapped using microelectrode recording techniques. This methodology ensured that the injections were well within the borders of each cortical field that was studied and enabled the elucidation of the topographies of the projections of AI and AAF onto the IC with respect to their cochleotopic organizations. The projection of loci in AI to the caudal aspect of the IC was in the form of sheets of terminals in the dorsomedial division of the central nucleus bilaterally and the pericentral nucleus ipsilaterally. The topography of projection with respect to the cochleotopic organizaton of AI appeared to be in register with the described cochleotopic organization of the central nucleus and the pericentral nucleus. The sheets of labeled terminals in the dorsemedial division of the central nucleus that resulted from the projection of single loci in AI were of the proper orientation to be continuous with the morphological laminae described in the ventrolateral division of the central nucleus. These sheets of corticocollicular terminals also paralleled the dorsomedial aspect of the physiolocally defined "isofrequency contours" of the central nucleus. Single injections placed in AAF produced autoradiographic label in the IC that was of the same basic pattern and systematic topography as the labeling recorded with AI injections; however, it was much weaker. The projection from AII was to the lateral (ipsilateral) and medial (bilateral) aspects of the pericentral nucleus.

Animals↗