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Biomedical subjects

P Lund

Publications and source records attributed to P Lund.

At least 19 recordsLinked to original sources
PubMed2001

Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant tumours worldwide, but molecular changes of tumour DNA, with the exception of viral integrations and p53 mutations, are poorly understood. In order to search for common macro-imbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by comparative genomic hybridization (CGH), subsequent database analyses and in selected cases by fluorescence in situ hybridization (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of genomic material, while losses were most prevalent in subregions of 4q, 6q, 13q and 16q. Deleted regions encompass tumour suppressor genes, like RB-1 and the cadherin gene cluster, some of them previously identified as potential target genes in HCC development. Several potential growth- or transformation-promoting genes located in chromosomal subregions showed frequent gains of genomic material. The present study provides a basis for further genomic and expression analyses in HCCs and in addition suggests chromosome 4q to carry a so far unidentified tumour suppressor gene relevant for HCC development.

Carcinoma, Hepatocellular↗
PubMed2001

Effect of randomization of mixtures of butter oil and vegetable oil on absorption and lipid metabolism in rats.

BACKGROUND: The nutritional effect of the regiospecific distribution of fatty acids in edible fats is currently discussed due to an increased use of interesterification of fats for human consumption. However, disagreeing results have been reported which may be due to the varying composition of the dietary fats compared. Data on the fate of such lipids beyond the bloodstream is rather scarce and animal model studies are needed. AIM OF THE STUDY: To compare the metabolism of butter oil and mixtures of butter and rapeseed oil, native or randomized, in a rat model. The regiospecific fatty acid distribution present in dietary fats was followed through absorption, chylomicron formation, and deposition in adipose tissue and in different liver lipids (triacylglycerols, phosholipids, and cholesterol esters). METHODS: Rats were fed for 6 weeks from weaning either butter oil (BO), a butteroil-rapeseed oil mixture 65:35 w/w (BR) or a randomized mixture of BR (tBR). Half of the animals were used for organ analysis, the rest for a postprandial study with the same fats and isolation of chylomicrons. The regiospecific distribution of the fatty acids present in the dietary fats was followed during metabolism by analyses of chylomicrons, depot fat and liver lipids, using regiospecific cleavage followed by TLC separation and quantification by GC. RESULTS: Randomization of edible fat mixtures leading to equal distribution of fatty acids between TG positions is directly reflected in the composition of chylomicrons. During clearing by lipoprotein lipase this positional distribution is abolished and the regiospecific composition of triacylglycerols in adipose tissue is completely identical for BR and tBR. Chylomicron remnants, which are taken up by the liver, are correspondingly fully degraded to free fatty acids by hepatic lipase, and distribution of fatty acids in liver triacylglycerols, phospholipids and cholesterol esters are identical for the groups fed either BR or tBR. The group fed BO with a low content of linoleic acid is on the borderline of essential fatty acid-deficiency. CONCLUSION: Randomization (interesterification) of butter oil with rapeseed oil (65:35 w/w) for use as edible fat did not have any impact on the fatty acid composition beyond the chylomicron step when compared to the native mixture.

Adipose Tissue↗
PubMed2001

Convalescence and driver reaction time after tension-free inguinal hernia repair.

To obtain an objective basis for a policy on the advice to patients on when to drive after anterior tension-free hernia repair. Foot reaction time before operation and on the 2nd postoperative day in 20 skilled male drivers with a right inguinal hernia was measured and compared with that of 30 normal subjects. The tests in a car simulator indicated that an untreated right inguinal hernia had no effect on emergency stop reaction time and that a plug-mesh hernia repair did not impair reaction time on the 2nd postoperative day (P>0.30). Average visual analogue pain scores on the 2nd and 4th postoperative days were 2.3 and 1.7, respectively. On the 8th postoperative day 18 patients had returned to normal activity and work. There was no recurrences after a mean postoperative time of 18 months. These data suggest that open tension-free hernia repair allows return to normal activities and car driving within a few days of the operation.

Journal Article↗
PubMed2001

Lipid oxidation in fish oil enriched mayonnaise: calcium disodium ethylenediaminetetraacetate, but not gallic acid, strongly inhibited oxidative deterioration.

The antioxidative effects of gallic acid, EDTA, and extra emulsifier Panodan DATEM TR in mayonnaise enriched with 16% fish oil were investigated. EDTA reduced the formation of free radicals, lipid hydroperoxides, volatiles, and fishy and rancid off-flavors. The antioxidative effect of EDTA was attributed to its ability to chelate free metal ions and iron from egg yolk located at the oil-water interface. Gallic acid reduced the levels of both free radicals and lipid hydroperoxides but promoted slightly the oxidative flavor deterioration in mayonnaise and influenced the profile of volatiles. Gallic acid may therefore promote the decomposition of lipid hydroperoxides to volatile oxidation products. Addition of extra emulsifier reduced the lipid hydroperoxide levels but did not influence the level of free radicals or the oxidative flavor deterioration in mayonnaisse; however, it appeared to alter the profile of volatiles. The effect of the emulsifier on the physical structure and rheological properties depended on the presence of antioxidants.

Antioxidants↗
PubMed2001

Two polymorphs of aqua[N,N'-ethylenebis(salicylideneaminato-N,O)]-oxovanadium(V) nitrate.

The title compound, aqua[bis(salicylidene)ethylenediaminato-O,N,N',O']oxovanadium(V) nitrate, [VO(C(16)H(14)N(2)O(2))(H(2)O)]NO(3), crystallizes as two polymorphs in the triclinic and monoclinic crystal systems. In both, the V atom has a distorted octahedral coordination geometry with a long V--O(water) bond trans to V==O. The coordinated water molecules are hydrogen bonded to the nitrate ions so that pairs of cations are linked to give neutral centrosymmetric dimers. The V==O and V--O(water) distances are 1.598 (2) and 2.257 (2) A, respectively, in the triclinic form, and 1.588 (3) and 2.230 (3) A, respectively, in the monoclinic form. In the triclinic form, the dimers pack so that the salen [bis(salicylidene)ethylenediaminate] ligands are parallel to each other, whereas in the monoclinic form, which is the denser, there is a herring-bone arrangement.

Journal Article↗
PubMed2000

Femoral neck buttressing: a radiographic and histologic analysis.

OBJECTIVE: To examine the incidence, radiographic and histologic findings of medial femoral neck buttressing in a consecutive group of patients undergoing total hip arthroplasty. DESIGN: Biomechanical parameters were evaluated on standard anteroposterior pelvic radiographs of 113 patients prior to hip replacement surgery. Demographic information on all patients was reviewed and histologic evaluation was performed on specimens obtained at the time of surgery. RESULTS: The incidence of medial femoral neck buttressing was found to be 50% in a consecutive series of patients undergoing total hip arthroplasty. The incidence was slightly higher in women (56% vs. 41%). Patients with buttressing had increased neck-shaft angles and smaller femoral neck diameters than were seen in patients without buttressing. Histologic evaluation demonstrated that the buttress resulted from deposition bone by the periosteum on the femoral neck in the absence of any evidence of femoral neck fracture. CONCLUSION: It would appear that femoral neck buttressing occurs in response to increased joint reactive forces seen at the hip being transmitted through the femoral neck. The increased joint reactive force can be related to the increased neck shaft angle seen in patients with buttressing.

Aged↗
PubMed2000

Determination of neutral lipid hydroperoxides by size exclusion HPLC with fluorometric detection. Application to fish oil enriched mayonnaises during storage.

A fast (12 min) high-performance size exclusion chromatography (HPSEC) method for the separation of neutral lipid class hydroperoxides in the oil phases from fish oil enriched mayonnaises was developed. Detection and quantification were performed using the postcolumn fluorometric (FL) diphenyl-1-pyrenylphosphine oxidation principle. The reproducibilities judged by intra- and inter-assay variations were 0.64 and 7.2%, respectively. The HPSEC-FL method was applied to assess the effect of supplementations with emulsifier, gallic acid, and EDTA on the oxidative processes in the mayonnaises during storage. Substantial amounts of hydroperoxy triacylglycerols (TAGOOH) and cholesterol esters (CEOOH), together with traces of TAGOOH-dimers, were detected. All supplementations significantly decreased the levels of TAGOOH and to a lesser degree CEOOH. Supplementations with EDTA and gallic acid resulted in constant and slightly increasing levels of TAGOOH, respectively, thus affecting the oxidation mechanisms seen in reference mayonnaise. The emulsifier Panodan TR DATEM reduced the levels of TAGOOH as compared to the appropriate controls.

Chromatography, High Pressure Liquid↗
PubMed2000

Dynamic headspace gas chromatography/mass spectrometry characterization of volatiles produced in fish oil enriched mayonnaise during storage.

Protection against lipid oxidation and formation of unpleasant fishy and rancid off-flavors in oil-in-water food emulsions, such as fish oil enriched mayonnaise, is difficult to achieve. Volatile profiles from stored mayonnaises with different oil phase compositions were collected using a developed dynamic headspace sampling technique, in which interfering acetic acid was removed in situ with potassium hydroxide, and subsequently 148 volatiles were characterized and monitored by gas chromatography/mass spectrometry. Multivariate statistics showed correlation between the concentration of 62 volatiles and the fish oil and storage parameters, indicating the formation of lipid oxidation products, which impose fishy off-flavors. Further verification was obtained by gas chromatography/olfactometry, by which, among 78 odors, cis-4-heptenal and trans,cis-2,4-heptadienal were detected as distinct fishy notes. In total, 27 volatiles, including 1-penten-3-one, cis-2-penten-1-ol, cis-3-hexenal, cis-4-heptenal, 1-octen-3-one, 1,cis-5-octadien-3-one, 1-octen-3-ol, trans,cis-2, 4-heptadienal, and trans,cis-2,6-nonadienal, were suggested to contribute to the developed unpleasant fishy and rancid off-flavors.

Fish Oils↗
PubMed1999

Effects of butter oil blends with increased concentrations of stearic, oleic and linolenic acid on blood lipids in young adults.

OBJECTIVE: The aim of this present project was to evaluate a more satisfactory effect on plasma lipoprotein profile of spreads based on dairy fat. DESIGN: This study was designed as a randomised cross-over experiment with a three-week treatment separated by a three-week wash-out period. Sixty five grams of the fat content of the habitual diets was replaced by either butter/grapeseed oil (90:10) (BG); butter oil and low erucic rapeseed oil (65:35) (BR) or butter blended in a 1:1 ratio with a interesterified mixture of rapeseed oil and fully hydrogenated rapeseed oil (70: 30) (BS). SUBJECTS: Thirteen healthy free-living young men (age 21-26 y) fulfilled the study. INTERVENTIONS: At the beginning and end of each diet period two venous blood samples were collected. Triacylglycerol and cholesterol concentrations in total plasma and VLDL, LDL, IDL and HDL fractions were measured, as were apo A-1 and apo B concentrations. Fatty acid composition of plasma phospholipids, plasma cholesterol ester and platelets was also determined. RESULTS: Significantly (P < 0.05) lower total and LDL-cholesterol concentrations were observed after the BR and BS period, compared to BG. The effect of BR and BS did not differ. BG and BR resulted in equal concentrations of HDL-C, but significantly higher than BS. Consequently, a significantly lower LDL-C/HDL-C ratio was seen after the BR treatment compared to BG and BS. Apo A-1 concentrations were not significantly different, but Apo B was significantly increased after BG. CONCLUSIONS: Partially replacing milk fat with rapeseed oil seems to yield a more healthy spread. Stearic acid had a HDL-C lowering effect compared to milk fat, but did not affect LDL-C significantly. The addition of stearic acid did not improve the plasma lipoprotein profile for young men with low cholesterol levels.

Adult↗
PubMed1998

Transgenic systems in studies on genotoxicity of alkylating agents: critical lesions, thresholds and defense mechanisms.

Transgenic systems, both cell lines and mice with gain or loss of function, are being used in order to modulate the expression of DNA repair proteins, thus allowing to assess their contribution to the defense against genotoxic mutagens and carcinogens. In this review, questions have been addressed concerning the use of transgenic systems in elucidating critical primary DNA lesions, their conversion into genotoxic endpoints, low-dose effects, and the relative contribution of individual cellular functions in defense. It has been shown that the repair protein alkyltransferase (MGMT) is decisive for protection against methylating and chloroethylating compounds. Protection pertains also to tumor formation, as revealed by the response of MGMT transgenic and knockout mice. Overexpression of genes involved in base excision repair (N-methylpurine-DNA glycosylase, apurinic endonuclease, DNA polymerase beta) is in most cases not beneficial in increasing the protection level, whereas their down-modulation or inactivation increases cellular sensitivity. This indicates that non-repaired base N-alkylation lesions and/or repair intermediates possess genotoxic potential. Modulation of mismatch repair and poly(ADP)ribosyl transferase has also been shown to affect the cellular response to alkylating agents. Furthermore, the role of Fos, Jun and p53 in cellular defense against alkylating mutagens is discussed.

Alkylating Agents↗
PubMed1998

How the new Hologic hip normal reference values affect the densitometric diagnosis of osteoporosis.

In February 1997, Hologic supplied new software to all QDR dual-energy X-ray absorptiometry (DXA) machines replacing the previous femoral normative reference database with the NHANES III normative data. In addition to changing the normative database (and therefore T-scores) for all regions of the hip, the new software has changed the primary region of interest from the femoral neck to the total hip. In the present study we examined how these changes influence the densitometric diagnosis of osteoporosis in a large clinical referral population (n = 2311, mean age 62.7 years). The patients had spine and hip DXA performed at either of two centers using a Hologic QDR-2000 over a 4-year period. T-scores were derived for each patient using both previous and current young normal reference databases. Intraindividual differences in T-scores were calculated. The prevalence of osteoporosis based on the two normative databases and the difference between the prevalence was calculated for each skeletal site. The average paired difference between current and previous T-scores at femoral neck is 0.64, the difference increasing with age. Using the new normative database, the percentage of osteoporotic patients decreases from 49% of all patients at the femoral neck to 28% at the femoral neck and 20% at the total hip. In conclusion, the densitometric diagnosis of osteoporosis will be affected in a significant proportion of women as a result of the implementation of the new hip normative database supplied by Hologic. Whether this will translate into fewer patients being treated remains to be seen.

Absorptiometry, Photon↗
PubMed1998

Effect of formula supplemented with docosahexaenoic acid and gamma-linolenic acid on fatty acid status and visual acuity in term infants.

BACKGROUND: Docosahexaenoic acid is present in high concentration in retina and does not influence visual development in preterm infants. It is still under discussion whether docosahexaenoic acid is important for visual development in term infants. METHODS: Thirty-seven infants fed formula for a median of 14 days were randomized at median age of 25 days to three formulas: a) DHAGF: 0.3 wt% docosahexaenoic acid and 0.5 wt% gamma-linolenic acid; b) DHAF 0.3 wt% docosahexaenoic acid; or c) STF: standard formula without long-chain polyunsaturated fatty acids and 17 breast-fed infants were observed, using blood samples and anthropometric measurements from 1 to 4 months of age. At 4 months, visual acuity was measured by swept steady-state visual evoked potential. A cross-sectional study on 25 breast-fed infants was carried out as a reference group for the analyses. RESULTS: Infants fed the two docosahexaenoic acid-supplemented formula had relative docosahexaenoic acid concentrations in red blood cell phospholipids almost as high as those in breast-fed infants, whereas infants in the standard formula group had significantly lower levels. The addition of gamma-linolenic acid to the formula had a positive effect on red blood cell arachidonic acid levels, compared with levels obtained using fish oil only. Visual acuity was significantly different among all feeding groups (analysis of variance; p = 0.05, means +/- standard deviation: breast-fed, 0.37+/-0.06 logMAR; DHAF and DHAGF combined, 0.40+/-0.07 logMAR; and standard formula 0.44+/-0.07 logMAR. However, there was no statistical difference among the formula groups. In a multiple regression analysis including all formula-fed infants, weight at delivery (p = 0.002), but not type of formula, was significantly associated with visual acuity at 4 months of age. CONCLUSIONS: The addition of docosahexaenoic acid resulted in concentrations in red blood cells at similar levels as those in breast-fed infants, whereas the increase in visual acuity did not reach significance. The addition of gamma-linolenic acid resulted in higher arachidonic acid concentrations in red blood cells.

Anthropometry↗
PubMed1997

Cavernous hemangiomas of the liver: enlargement over time.

OBJECTIVE: It has been reported that cavernous hemangiomas of the liver either do not enlarge over time, or, of the very few lesions that have shown an increase in diameter on follow-up imaging studies, the increase has been minimal. The objective of this paper is to report growth of four cavernous hemangiomas that were shown to have doubled to tripled in diameter on follow-up imaging studies done between 34 months and 10.5 years after the initial diagnosis. CONCLUSION: This report indicates that hepatic hemangiomas can grow significantly in diameter, although such growth is unusual. Despite the growth of the lesion, however, if the imaging features are characteristic of hemangioma an imaging diagnosis can still be made confidently.

Adult↗
PubMed1996

Intrinsic fluorescence studies of the chaperonin GroEL containing single Tyr --> Trp replacements reveal ligand-induced conformational changes.

Two mutants of GroEL containing the single tyrosine to tryptophan replacement of either residue 203 or 360 in the apical domain have been purified, characterized, and used for fluorescence studies. Both mutants can facilitate the in vitro refolding of rhodanese in an ATP- and GroES-dependent manner, producing yields of recoverable activity comparable to the wild-type chaperonin. Y203W shows some increased hydrophobic exposure and easier urea-induced disassembly compared with wild-type or Y360W, although the unfolding of all the species was similar at high concentrations of urea. Intrinsic fluorescence studies of the two mutants reveal that nucleotide binding (ADP or AMP-PNP (adenosine 5'-(beta,gamma-imino)triphosphate)) induces conformational changes in the tetradecamer that are independent of the presence of the co-chaperonin, GroES. The K1/2 for this transition is approximately 5 microM for both mutants. Energy transfer experiments show that the tryptophan fluorescence of the Y360W mutant is partially quenched ( approximately 50%) upon binding of the fluorescent, hydrophobic probe 4,4'-bis(1-anilino-8-naphthalenesulfonic acid), while the fluorescence of the Y203W mutant is significantly quenched ( approximately 75%). These results are discussed in relation to the molecular mechanism for GroEL function.

Adenosine Diphosphate↗
PubMed1996

Visual acuity and erythrocyte docosahexaenoic acid status in breast-fed and formula-fed term infants during the first four months of life.

It has been recognized that preterm infants have a more rapid development of visual acuity if fed human milk or a formula enriched with the long-chain polyunsaturated fatty acid (LCPUFA) docosahexaenoic acid (DHA) compared to a standard formula devoid of LCPUFA. Few studies have addressed whether the same is also true in term infants. The aim of the present study was to follow visual acuity and fatty acid composition in red blood cells (RBC) for the first 4 mon of life in 17 breast-fed and 16 formula-fed term infants. The formula used did not contain LCPUFA, but contained 1.7 wt% alpha-linolenic acid, and the linoleic/alpha-linolenic acid ratio was 8.5. The increase in visual acuity measured by Teller acuity cards developed more rapidly in breast-fed infants compared to formula-fed infants (P < 0.001). This was parallelled by a decrease in DHA of RBC in formula-fed infants, and with a significantly lower level at two and four months as compared to breast-fed infants. The content of DHA in milk from the breast-feeding mothers was high compared to other Western countries. The difference in visual acuity between the two feeding groups could be due to differences in DHA status as reflected by the RBC levels, but other explanations are possible. Intervention studies are required to verify if development of visual acuity in term formula-fed infants is dependent on the DHA level of formula.

Breast Feeding↗
PubMed1995

Expression of LacZ from the htrA, nirB and groE promoters in a Salmonella vaccine strain: influence of growth in mammalian cells.

Attenuated Salmonella strains are currently being evaluated as live vectors for the delivery of heterologous antigens to the mammalian mucosal and systemic immune systems. An approach to improving the stability of heterologous antigen expression during vaccination is to drive expression of the foreign protein from promoters, e.g. nirB, that become activated when Salmonella enter the host. Salmonella strains were constructed that harboured similar multicopy plasmids encoding the lacZ gene. In each strain, lacZ expression was driven from either the nirB, htrA or groE promoters. Expression of LacZ increased in all vaccine strains as they were shifted from conditions of low to high temperature. In addition, expression of lacZ driven from the htrA and nirB promoters significantly increased when the Salmonella entered eukaryotic cells, including macrophages. Expression of lacZ from the groE promoter was significantly elevated in macrophages but not in cells derived from epithelia. These promoters may be useful for optimising heterologous antigen expression within immune cells of the host.

Antigens↗