Search PubMed⌕ Search

Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 37 records · Page 2Linked to original sources
PubMed2001

Association between apolipoprotein B promotor haplotypes and cholesterol status.

Association between apolipoprotein B (apo B) promoter haplotypes and cholesterol concentration was studied in two groups of children with low and high concentrations of cholesterol. Strong linkage equilibrium was demonstrated between I/D in the signal peptide of apo B and (C-516T) polymorphism in the promotor of apo B gene, and the I/I+ allele T haplotype was associated with a low cholesterol concentration.

Apolipoproteins B↗
PubMed2001

5-Aminolaevulinic acid methyl ester transport on amino acid carriers in a human colon adenocarcinoma cell line.

The transport mechanisms of 5-aminolevulinic acid methyl ester (5-ALA-ME) have been studied in a human adenocarcinoma cell line (WiDr) by means of 14[C]-labeled 5-ALA-ME. The transport was found to be partly Na+ dependent, while the extracellular Cl- concentration did not affect the uptake. The transport of 5-ALA-ME into WiDr cells was dependent on the incubation temperature and was found to be completely blocked by the inhibitors of energy metabolism, 2-deoxyglucose and sodium azide. WiDr cells were treated with 10 mM of 14 different amino acids and the substrate specificity of the 5-ALA-ME transporter(s) was analyzed by treating the cells with 23 microM or 1 mM 14[C]-labeled 5-ALA-ME. The transport of 5-ALA-ME was found to be inhibited to the highest extent, i.e. about 60%, by the nonpolar amino acids L-alanine, L-methionine, L-tryptophan and glycine. The uptake of 5-ALA-ME followed an exponential decay with increasing concentration of glycine, reaching a maximum inhibition of uptake of 5-ALA-ME of 55%. Sarcosine, a specific inhibitor of system Gly, did not significantly inhibit 5-ALA-ME transport. In contrast to transport of 5-ALA, 5-ALA-ME does not seem to be taken up by system BETA transporters. In conclusion, the cellular uptake of 5-ALA-ME into WiDr cells seems to be due to active transport mechanisms, involving transporters of nonpolar amino acids.

Adenocarcinoma↗
PubMed2001

Evaluation of different photosensitizers for use in photochemical gene transfection.

Many potentially therapeutic macromolecules, e.g. transgenes used in gene therapy, are taken into the cells by endocytosis, and have to be liberated from endocytic vesicles in order to express a therapeutic function. To achieve this we have developed a new technology, named photochemical internalization (PCI), based on photochemical reactions inducing rupture of endocytic vesicles. The aim of this study was to clarify which properties of photosensitizers are important for obtaining the PCI effect improving gene transfection. The photochemical effect on transfection of human melanoma THX cells has been studied employing photosensitizers with different physicochemical properties and using two gene delivery vectors: the cationic polypeptide polylysine and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Photochemical treatment by photosensitizers that do not localize in endocytic vesicles (tetra[3-hydroxyphenyl]porphyrin and 5-aminolevulinic acid-induced protoporphyrin IX) do not stimulate transfection, irrespective of the gene delivery vector. In contrast, photosensitizers localized in endocytic vesicles stimulate polylysine-mediated transfection, and amphiphilic photosensitizers (disulfonated aluminium phthalocyanine [AlPcS2a] and meso-tetraphenylporphynes) show the strongest positive effect, inducing approximately 10-fold increase in transfection efficiency. In contrast, DOTAP-mediated transfection is inhibited by all photochemical treatments irrespective of the photosensitizer used. Neither AlPcS2a nor Photofrin affects the uptake of the transfecting DNA over the plasma membrane, therefore photochemical permeabilization of endocytic vesicles seems to be the most likely mechanism responsible for the positive PCI effect on gene transfection.

Aminolevulinic Acid↗
PubMed2001

5-Aminolevulinic acid-based photochemical internalization of the immunotoxin MOC31-gelonin generates synergistic cytotoxic effects in vitro.

Photochemical internalization (PCI) is a novel method for the endosomal or lysosomal release of membrane-impermeable molecules into the cytosol of target cells. This novel technology is based on the photodynamically induced rupture of endocytic vesicles preloaded with molecules of therapeutic interest. PCI of the ribosome-inactivating plant toxin gelonin and the immunotoxin monoclonal antibody 31 (MOC31) gelonin has been performed previously by the use of the endocytic vesicle-localizing photosensitizers TPPS2a and AIPcS2a and light, demonstrating synergistic toxicity against the more than 20 different cell lines tested, most of them of neoplastic origin. In this study we demonstrate that 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) is also capable of inducing PCI of MOC31-gelonin in the human colon adenocarcinoma cell line WiDr. The cells were incubated with 1 mM 5-ALA for up to 8 h in serum-free medium and from 24 to 96 h in serum-containing medium. Fluorescence microscopical studies indicate a partial plasma membrane localization of PpIX when 5-ALA was applied under serum-free conditions. This plasma membrane localization was not seen when 5-ALA was given in the presence of serum. There was a granular component of the PpIX localization in addition to a diffuse cytoplasmic localization. The granular component resembled the localization of the fluorescent dye conjugate Alexa-gelonin and the lysosomal localizing dye acridine orange. Our present results provide evidence for an endocytic vesicle-associated fraction of PpIX after 5-ALA incubation of the WiDr cells. We demonstrate that PCI, by combining 5-ALA, MOC31-gelonin and light, induces a synergistic cytotoxic effect against the WiDr cells.

Acetylglucosaminidase↗
PubMed2001

A new assessment for elders admitted to acute care: reliability of the MDS-AC.

Assessment of older people rarely includes functional domains critical for ensuring optimum outcome of treatment in acute hospital care. We report the development of a new assessment instrument, and illustrate how differences between pre-hospital and hospital admission status can be systematically evaluated using the Minimum Data Set for Acute Care (MDS-AC). Content was developed by literature review and consultation with professionals working in acute areas. Dual independent assessments were conducted on hospital in-patients in 4 countries. Inter-assessor reliability coefficients were calculated for each item. Kappa was calculated for all binary and multi-level nominal variables. Quadratically weighted Kappa was estimated for all ordinal multi-level variables. Where one level of the variable contained 90% or more of the subjects, total observed agreement is reported. Separate reliability estimates were calculated for pre-hospitalization and inpatient items. Subjects had a mean age of 78. Completion of pre-hospitalization and hospital period assessment (combined) required 20 and 30 minutes. Excluding items for which 90% or more of subjects were classified into a single scoring level, average inter-assessor reliability coefficient for the pre-hospital period items was 0.57 and for in hospital 0.58. Overall exact agreement was 83% for pre-hospitalization assessment items, and 79% for the in-hospital items. The reliability achieved in the highly unstable situation of the acute admission phase is sufficient for use in clinical care and research. Differences in pre-hospital and admission status necessary for case-mix adjusted comparison of outcomes were illustrated. Development of a means for systematically comparing changes in older people during the course of illness is of increasing importance when addressing questions of the appropriate and inappropriate use of medical technology.

Activities of Daily Living↗
PubMed2001

Comparison of active and passive recovery of blood lactate and subsequent performance of repeated work bouts in ice hockey players.

This study examined the effect of active and passive recovery on lactate concentration and subsequent performance of repeated work bouts in 18 male NCAA Division I ice hockey players. Using a repeated measures design, subjects performed a series of skating tests before and after a 15-minute recovery. The skating test consisted of skating a course for 7 shifts, which lasted 40 seconds per shift with 90 seconds rest between shifts. Active recovery (low-intensity cycling) and passive recovery (sitting) lasted for 15 minutes and were followed by an identical 7-shift skating test. Passive vs. active recovery showed no statistically significant differences for distance skated, heart rate, or lactate. There appeared to be a trend for greater skating distance in period 2 when active recovery was used, but the difference was not significant (p > 0.05). It was concluded that active recovery did not enhance lactate removal or subsequent performance of repeated work bouts in simulated hockey play.

Adult↗
PubMed2001

The relationship between field tests of anaerobic power and 10-km run performance.

The purpose of this study was to investigate the relationship between several field tests of anaerobic power and distance running performance. Thirty-six trained runners (20 men and 16 women; mean +/- SD age, 27.9 +/- 5.7 years) participated in this study. Tests of anaerobic power consisted of a 50-m sprint, vertical jumps from a static take-off position and with a countermovement, a plyometric leap test, and a 300-m sprint. The results indicated that gender, height, weight, percent body fat, 50-m sprint time, the height and power of both types of vertical jumps, plyometric leap distance, and the 300-m sprint time were significantly correlated with 10-km run time (p < or = 0.05) in the total subject pool (N = 36). Stepwise multiple regression identified the plyometric leap distance to explain 73.9% of the variance in run time. When combined with 300-m sprint time, 77.9% of the variance (standard error of the estimate, 2.92 minutes) was explained. The regression equation developed is Y' (10-km time) = 57.22 - 5.15(plyometric leap distance in meters) + 0.27(300-m sprint time in seconds). The results indicate that anaerobic power is significantly related to distance running performance and may explain a meaningful percentage of variability in 10-km run time. Therefore, it may be beneficial for distance runners to supplement aerobic training with some power and speed development such as plyometrics and sprinting.

Adult↗
PubMed2001

African-American heredity prostate cancer study: a model for genetic research.

A genome-wide scan of high-risk prostate cancer families in North America has demonstrated linkage of a particular marker to Chromosome Iq (HPC11. An even greater proportion of African-American families have shown linkage to HPC 1. Therefore, investigators at the National Human Genome Research Institute [NHGRI] in collaboration with Howard University and a predominantly African-American group of urologists established the African-American Hereditary Prostate Cancer (AAHPC) Study Network to confirm the suggested linkage of HPC in African Americans with a gene on Chromosome 1. Blood samples from recruited families were sent to Howard University for extraction of DNA. The DNA was sent to NHGRI at NIH where the genotyping and genetic sequence analysis was conducted. Genotype data are merged with pedigree information so that statistical analysis can be performed to establish potential linkage. From March 1, 1998, to June 1, 1999, a total of 40 African-American families have been recruited who met the study criteria. Preliminary results suggest that racial/ethnicity grouping may affect the incidence and extent of linkage of prostate cancer to specific loci. The importance of these findings lays in the future treatment of genetic-based diseases.

Black People↗
PubMed2000

Autosomal dominant myopathy: missense mutation (Glu-706 --> Lys) in the myosin heavy chain IIa gene.

We here report on a human myopathy associated with a mutation in a fast myosin heavy chain (MyHC) gene, and also the genetic defect in a hereditary inclusion body myopathy. The disorder has previously been described in a family with an "autosomal dominant myopathy, with joint contractures, ophthalmoplegia, and rimmed vacuoles." Linkage analysis and radiation hybrid mapping showed that the gene locus (Human Genome Map locus name: IBM3) is situated in a 2-Mb region of chromosome 17p13, where also a cluster of MyHC genes is located. These include the genes encoding embryonic, IIa, IIx/d, IIb, perinatal, and extraocular MyHCs. Morphological analysis of muscle biopsies from patients from the family indicated to us that the type 2A fibers frequently were abnormal, whereas other fiber types appeared normal. This observation prompted us to investigate the MyHC-IIa gene, since MyHC-IIa is the major isoform in type 2A fibers. The complete genomic sequence for this gene was deduced by using an "in silico" strategy. The gene, found to consist of 38 exons, was subjected to a complete mutation scan in patients and controls. We identified a missense mutation, Glu-706 --> Lys, which is located in a highly conserved region of the motor domain, the so-called SH1 helix region. By conformational changes this region communicates activity at the nucleotide-binding site to the neck region, resulting in the lever arm swing. The mutation in this region is likely to result in a dysfunctional myosin, compatible with the disorder in the family.

Adult↗
PubMed2000

5-aminolevulinic acid induced lipid peroxidation after light exposure on human colon carcinoma cells and effects of alpha-tocopherol treatment.

This work relates to studies on modes of phototoxicity by protoporphyrin (PpIX) after incubation of 5-aminolevulinic acid (5-ALA) on cultured cells. Lipid peroxidation in the 5-ALA incubated primary adenocarcinoma cells from the rectosigmoid colon (WiDr cells) was determined by measurement of protein-associated thiobarbituric acid reactive substances (TBARS). TBARS were increased 2-fold in cells treated with 2 mM 5-ALA for 3.5 h in serum enriched medium. After illumination of 5-ALA incubated cells, TBARS were formed in a light dose dependent manner. TBARS analysis were compared with high-performance liquid chromatography (HPLC) analysis of malondialdehyde, and results indicate that 90% of the thiobarbituric reactive substances were due to malondialdehyde. Pretreating WiDr cells with alpha-tocopherol for 48 h inhibits the cytotoxic effect of 5-ALA and increases 5-fold the light dose needed to kill 50% of the cells. Pretreatment with alpha-tocopherol shows a considerable decrease (about 80%) on TBARS formation after illumination. The cellular content of alpha-tocopherol was determined by HPLC and found to be 15.3 pmol/10(6) cells.

Adenocarcinoma↗
PubMed2000

Photochemical internalisation increases the cytotoxic effect of the immunotoxin MOC31-gelonin.

Photochemical internalisation (PCI) was recently demonstrated as a unique procedure for site-specific delivery of several types of membrane impermeable macromolecules from endocytotic vesicles to the cytosol (Berg et al., 1999). The technology is based on the cytosolic release of endocytosed macromolecules from endosomes and lysosomes upon exposure of cells to photosensitising compounds, which became localised to these vesicles, and light. In our study the possibility to increase the cytotoxic effect of the immunotoxin MOC31-gelonin by PCI was examined. The type I ribosome-inactivating protein gelonin was covalently linked to the monoclonal IgG1 antibody MOC31, directed against epithelial glycoprotein-2 (EGP-2), an antigen expressed on most carcinoma cells. Five different cell lines, of which 4 expressed EGP-2, were treated with MOC31-gelonin and endosomal and lysosomal localising photosensitisers, followed by exposure to light. Insignificant cytotoxicity of the MOC31-gelonin was observed when the cells were incubated with the immunotoxin alone. However, in combination with endosomal and lysosomal localising photosensitizers, we demonstrate synergistic toxic effect of the MOC31-gelonin conjugate in a light-dependent manner. Our results indicate that PCI is a promising tool for increasing the cytotoxicity of immunotoxins, which is important for further improvement of the PCI concept towards possible use in cancer therapy.

Antibodies, Monoclonal↗
PubMed2000

[Diagnostic DNA testing for Huntington disease].

Direct DNA testing for the autosomal dominant neurodegenerative disorder, Huntington's disease, may be performed in a diagnostic setting, as a presymptomatic procedure or prenatally. This paper is intended for physicians practising outside departments of medical genetics who are considering diagnostic testing of patients presenting with symptoms or signs compatible with Huntington's disease. It offers a brief overview of practically relevant clinical, epidemiological, molecular and legal aspects of diagnostic genetic testing for Huntington's disease in Norway. We stress the need for adequate information before sampling and after the test has been performed, and for close contact with the genetics centre which offers the test for Huntington's disease and provides genetic counselling. As with other diagnostic tests, the treating physician is responsible for informing the patient about the result of the test and for ensuring adequate follow-up. The physician will often need the assistance of an expert in clinical genetics. A positive DNA test for Huntington's disease in a patient may have a profound impact on family members, who should be offered genetic counselling and support. Since asymptomatic at-risk family members may ask for a presymptomatic test in the future, diagnostic confirmation at the DNA level is warranted in any person examined because of clinical signs of Huntington's disease, even when the clinical diagnosis is considered unquestionable.

DNA Mutational Analysis↗
PubMed2000

[Genetic counseling in presymptomatic testing for Huntington disease].

Norwegian law and international guidelines require genetic counselling before, during and after presymptomatic testing for Huntington's disease. The genetic counselling of at-risk persons who considers taking tests, includes explanation of the possible implications of a test result for both participant and relatives. The test is performed only when explicitly requested by the participant and after informed consent. The participant decides if and when the test should be conducted. The participant also has major influence on the timing of the consecutive phases of the testing procedure, in compliance with medical and ethical recommendations. This paper reviews main issues raised during genetic counselling and the preparation period preceding the test and communication of the test result. We illustrate different individual situations and backgrounds for considering presymptomatic testing for Huntington's disease by describing three anonymized cases and associated pedigrees.

Adult↗
PubMed2000

Follow-up study of patients randomized in the Scandinavian simvastatin survival study (4S) of cholesterol lowering.

The Scandinavian Simvastatin Survival Study (4S) and other randomized clinical trials have demonstrated that cholesterol-lowering treatment with statins improves prognosis in patients with coronary atherosclerosis compared with placebo. The effect of therapy with statins beyond the typical 5 to 6 years' duration of the trials, in particular regarding the risk of cancer, has not been investigated. This study examines the long-term effects of simvastatin for up to 8 years on cause-specific mortality in patients with coronary heart disease (CHD). We performed an observational, government registry-based study of mortality in the groups originally randomized to simvastatin or placebo in the 4S over an additional 2-year follow-up period, so that the median total follow-up period was 7.4 years (range 6.9 to 8.3 in surviving patients). Randomization took place at outpatient clinics at 94 clinical centers in Denmark, Finland, Iceland, Norway, and Sweden from 1988 to 1989. Of 4,444 patients with CHD, 2,223 and 2,221 were randomized to treatment with placebo or simvastatin therapy, respectively. Patients received treatment with simvastatin, starting at 20 mg/day, with titration to 40 mg/day at 12 or 24 weeks if total cholesterol was >5.2 mmol/L (200 mg/dl), or placebo. After the double-blind period, most patients in both treatment groups received simvastatin as open-label prescription. Of the 1,967 patients originally treated with placebo and surviving the double-blind period, 97 (4.9%) died during the following 2 years. In the group randomized to simvastatin the corresponding number was 74 of the 2, 039 survivors (3.6%). Adding these deaths to those occurring during the original trial, the total was 353 (15.9%) and 256 (11.5%) deaths in the groups originally randomized to placebo and simvastatin, respectively. The relative risk was 0.70 (95% confidence interval 0. 60 to 0.82, p = 0.00002). The total number of cancer deaths was 68 (3.1%) in the placebo group and 52 (2.3%) in the simvastatin group (relative risk 0.73, 95% confidence interval 0.51 to 0.05, p = 0. 087), and the numbers of noncardiovascular and other deaths were similar in both groups. We therefore conclude that treatment with simvastatin for up to 8 years in patients with CHD is safe and yields continued survival benefit.

Adult↗
PubMed2000

Release of gelonin from endosomes and lysosomes to cytosol by photochemical internalization.

Gelonin, a type I ribosome-inactivating plant toxin, executes N-glycosidase activity on eukaryotic ribosomes. However, on intact cells, gelonin is relatively non-toxic, due to an incapability to penetrate cell membranes. Recently, a novel method, photochemical internalization (PCI), was invented for the translocation of membrane-impermeable molecules including gelonin to the cytosol [K. Berg et al., Cancer Res. 59 (1999) 1180-1183]. The combination of gelonin and photoactivation of endosomal and lysosomal localizing photosensitizers gives strong synergistic cytotoxic effects. In this study, we have evaluated the intracellular transport and stability of gelonin. By fluorescence microscopy, it was shown that gelonin co-localizes with the endosomal and lysosomal localizing photosensitizer, aluminum phthalocyanine with two sulfonate groups on adjacent phenyl rings, and both molecules re-localized to cytosol subsequently to light exposure. Gelonin accumulated in endosomal compartments by incubation at 18 degrees C was released to cytosol by PCI with concomitant inhibition of protein synthesis indicating that PCI can be executed through rupture of endosomal vesicles. The cathepsin inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanido)butane increased the cytotoxic effect of gelonin after PCI when gelonin was provided as a 2 h pulse followed by 4 h chase before PCI. Thus, although gelonin can enter the cytosol from lysosomes, lysosomal degradation is a limiting factor for the outcome of PCI of gelonin.

Cysteine Proteinase Inhibitors↗
PubMed2000

Observation of hot-electron pressure in the vibration dynamics of metal nanoparticles

We investigate the vibration dynamics of ellipsoidal silver nanoparticles, using time-resolved optical pump-probe spectroscopy. When excited with femtosecond laser pulses, the particles execute anisotropic shape oscillations. We show that these vibrations are triggered by the thermal expansion of the optically heated particles. The time dependence of the vibrations indicates that this expansion is caused by two mechanisms: The lattice anharmonicity and the extremely large pressure of the hot conduction electrons.

Journal Article↗
PubMed2000

Photochemical transfection: a new technology for light-induced, site-directed gene delivery.

The development of methods for specific delivery of therapeutic genes into target tissues is an important issue for the further progress of in vivo gene therapy. In this article we report on a novel technology, named photochemical transfection, to use light to direct a precise delivery of therapeutic genes to a desired location. The technology makes use of photosensitizing compounds that localize mainly in the membranes of endosomes and lysosomes. On illumination these membrane structures will be destroyed, releasing endocytosed DNA into the cell cytosol. Using a green fluorescent protein gene as a model we show that illumination of photosensitizer-treated cells induces a substantial increase in the efficiency of transfection by DNA-poly-L-lysine complexes. Thus, in a human melanoma cell line the light treatment can increase the transfection efficiency more than 20-fold, reaching transfection levels of about 50% of the surviving cells. In this article various parameters of importance for the use of this technology are examined, and the potential use of the technology in gene therapy is discussed.

Endosomes↗