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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 37 records · Page 2Linked to original sources
PubMed2002

Phylloerythrin. mechanisms for cellular uptake and location, photosensitisation and spectroscopic evaluation.

AIM: To elucidate the photobiological behaviour of phylloerythrin by studying the cellular uptake and intracellular localisation pattern of phylloerythrin and its spectral properties in Chinese hamster lung fibroblast cells (V79). METHODS: Phylloerythrin was diluted in dimethylsulfoxide (DMSO). Fluorescence emission and excitation spectra were measured using a luminescence spectrometer equipped with a red-sensitive photomultiplier. V79 cells were cultured in monolayers and labelled with 0.25 microg/ml phylloerythrin for uptake, cell survival and intracellular localisation studies. For cell survival and intracellular localisation studies, cells were subsequently exposed to blue light at a fluence rate of 9.0 mW/cm2. RESULTS: The fluorescence excitation spectrum of phylloerythrin in DMSO was characterised by a Soret band exhibiting a maximum peak at 418 nm. The fluorescence emission spectrum had peaks at 643 and 706 nm. The corresponding spectra in cells were red-shifted to 422, 650 and 712 nm, respectively. The cellular uptake of phylloerythrin was complete after about 10 h of incubation. The uptake together with the activation energy and analysis of cells incubated with phylloerythrin at 37 degrees C and 0 degrees C using fluorescence microscopy indicated that the dye is taken up into cells via a diffusion mediated pathway. Measurements of subcellular marker enzymes were performed immediately after light exposure of phylloerythrin-treated cells. The mitochondrial marker enzyme, cytochrome-c oxidase, and the marker enzyme for the Golgi apparatus, UDP galactosyl transferase, but not those for lysosomes, -N-acetyl-D-glucosaminidase (-AGA), and endoplasmic reticulum, NADPH cytochrome-c reductase, were inactivated upon photodynamic treatment. CONCLUSION: These results indicate that phylloerythrin is located mainly in the Golgi apparatus and mitochondria of V79 fibroblasts cells.

Journal Article↗
PubMed2001

In vivo documentation of photochemical internalization, a novel approach to site specific cancer therapy.

Photochemical internalization (PCI) is a unique procedure for site-specific delivery of several types of membrane-impermeable molecules to the cytosol of target cells. The technology is based on photochemical-induced release of endocytosed macromolecules from endosomes and lysosomes into the cytosol. The purpose of this study was to evaluate the therapeutic potential of PCI of the type I ribosomal-inactivating protein gelonin in an animal model. The photosensitizer aluminum phthalocyanine disulfonate (AlPcS(2a)) was injected intraperitoneally (10 mg/kg) into athymic female BALB/c (nu/nu) nude mice (8-9 mice per group) with subcutaneously growing human adenocarcinoma (WiDr) tumors 48 hr before exposure to 135 J/cm(2) of red light focused on the tumor. Six hours before light exposure a single dose of 50 microg gelonin was administrated intratumorally. Tumor growth was measured at least twice a week. After immunomagnetic separation of in vivo growing tumor cells the subcellular localization of the photosensitizer was evaluated by fluorescence microscopy. The photosensitizer localized in endocytic vesicles in in vivo growing WiDr cells. Furthermore, it was found that in vitro gelonin treatment of WiDr cells isolated from photosensitizer-treated mice potentiated a light-induced decrease of clonal survival. Complete remission in 6 of 9 (67%) of the treated mice were induced. Our findings indicate that photochemical treatment with the photosensitizer AlPcS(2a) activates the cytotoxic potential of gelonin in vivo. These results demonstrate that the synergistic effect of combining photoactivation of photosensitizer located in endocytic vesicles and gelonin is indeed a result of PCI of gelonin.

Animals↗
PubMed2001

[Gene therapy in cardiovascular diseases].

Cardiovascular disease is the most frequent cause of death in the western hemisphere. Although significant advances in pharmacotherapy have been achieved, the morbidity and mortality of cardiovascular disease will probably remain a scourge of affluent societies for many years to come. This situation gives the scientific community and the pharmaceutical industry an impetus to develop novel therapeutical strategies. Gene therapy is a principle which may provide new means of targeting the pathophysiological mechanisms of cardiovascular disease and has recently drawn a lot of scientific attention, as the endothelial cells of the vasculature are in direct contact with the blood. Thus, many of the obstacles which are thought to hamper gene delivery may not apply in this system. Although there are many ongoing gene therapy trials in this patient group, the results that have so far been reported are from early phase studies (phase I and II studies) only. The published reports have investigated to what extent the growth factors vascular endothelial growth factor and fibroblast growth factor may improve revascularization in ischaemic myocardial tissue. Although the preliminary results are promising, it should be pointed out that phase III trials have not yet been started in this disease group.

Cardiovascular Diseases↗
PubMed2001

In search of susceptibility genes for type 2 diabetes in West Africa: the design and results of the first phase of the AADM study.

PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.

Africa, Western↗
PubMed2001

Therapeutic electrical stimulation in cerebral palsy: a randomized, controlled, crossover trial.

The aim of this study was to evaluate the effect of therapeutic electrical stimulation (TES) applied to antagonists of spastic leg muscles on gross motor function in children with spastic diplegic cerebral palsy. Twelve children between 5 and 12 years of age completed a 24-month crossover study in which six were randomly assigned to receive TES for the first 12 months and the remaining six for the last 12 months. Physiotherapy and a home training program were not altered. All were evaluated blindly in terms of tests of motor function and video recordings at the start and at 12 and 24 months. At the end of the study parents/carers gave a subjective assessment of the effect of TES. No significant effect of TES on motor or ambulatory function was found on the blinded evaluation, but parents of 11 of the 12 children stated that TES had a significant effect. We conclude that it is unlikely that TES has a significant effect on motor and ambulatory function in spastic diplegia.

Cerebral Palsy↗
PubMed2001

Solidarity and equity: new ethical frameworks for genetic databases.

Genetic database initiatives have given rise to considerable debate about their potential harms and benefits. The question arises as to whether existing ethical frameworks are sufficient to mediate between the competing interests at stake. One approach is to strengthen mechanisms for obtaining informed consent and for protecting confidentiality. However, there is increasing interest in other ethical frameworks, involving solidarity--participation in research for the common good--and the sharing of the benefits of research.

Confidentiality↗
PubMed2001

Functional genomics, gene arrays, and the future of pathology.

The human genome project has attracted a great deal of attention in recent years among the general public as well as the scientific community. Although it is likely to be a number of years before many of the expected benefits of the genomics revolution are realized, the impact of these scientific breakthroughs on diagnostic pathology is likely to become apparent relatively quickly. In particular, gene array technology, which allows gene expression measurements of thousands of genes in parallel, provides a powerful tool for pathologists seeking new markers for diagnosis. Several recent studies demonstrate how the gene array approach can not only recognize markers for known categories of neoplasia but also lead to recognition of different categories not previously appreciated. Although this approach shows great potential, the successful application of gene arrays to diagnostic problems will require thoughtful interpretation, just as immunochemical technologies require careful planning and analysis.

DNA, Complementary↗
PubMed2001

Plasma fibrinogen level and long-term prognosis in Norwegian middle-aged patients with previous myocardial infarction. A 10 year follow-up study.

OBJECTIVES: To investigate the prognostic value of plasma fibrinogen level amongst middle-aged survivors of myocardial infarction (MI). DESIGN: Prospective cohort study. SETTINGS: Determination of fibrinogen and other prognostic variables in MI patients recruited in a presumably stable phase of coronary heart disease (CHD). SUBJECTS: A total of 247 middle-aged CHD patients (54 women and 193 men) who had their first MI at age < or = 60 (women) or < or = 55 (men) were recruited at least 3 months after (mean 2.1 years) the most recent MI. MAIN OUTCOME MEASURES: The primary endpoint was total mortality, and the secondary endpoint was cardiac deaths. The tertiary endpoint was major cardiac events (cardiac death, MI and cardiac arrest). RESULTS: During a follow-up period of 10 years a total of 44 patients had died, 36 from cardiac causes. Major cardiac event occurred in 70 patients. After adjusting for age, ejection fraction (EF), total serum cholesterol (TC), smoking and hypertension, patients in the top quartile of fibrinogen (> or = 4.0 g L-1) had a relative risk (RR) of 1.8 (95% CI 1.0-3.6) (P = 0.07) for death of all causes. The top quartile of fibrinogen was a stronger predictor of cardiac death; RR = 2.2 (95% CI 1.1-4.4) (P = 0.03), whilst the effect on the endpoint major cardiac event was not significant; RR=1.1 (95% CI 0.6-1.9) (P = 0.69). CONCLUSIONS: A plasma fibrinogen level in the top quartile predicted cardiac death in middle-aged patients who had suffered MI.

Female↗
PubMed2001

Polymorphisms in candidate genes for blood pressure regulation in young men with normal or elevated screening blood pressure.

We have previously shown correlations between cardiovascular risk factors such as blood pressure (BP), sympathetic nervous system activity, lipids and insulin resistance in young men with elevated screening BP. In the present study we aimed to: (1) compare the genotype distribution and allele frequencies of 11 polymorphisms in seven candidate genes for BP regulation in healthy 21-year-old Caucasian men, between 18 men with normal and 67 men with high screening BP, and (2) evaluate the effect of these polymorphisms in candidate genes on casual BP, BP responses to mental stress or catecholamines and metabolic parameters including insulin sensitivity. There were no differences in genotype distributions or allele frequencies between the subjects with normal and those with high screening BP. Insulin sensitivity was significantly higher in GG homozygotes in the G-261A polymorphism at the alpha 2A-adrenergic receptor (alpha(2A)AR) locus compared to GA heterozygotes (p = 0.007). Subjects who were homozygous both GG in the G-261A polymorphism at the alpha(2A)AR locus and GlyGly in the Arg16Gly polymorphism at the beta2-adrenergic (beta2AR) receptor loci had significantly higher insulin sensitivity and lower catecholamine levels during mental stress than subjects with other genotypes. Subjects who were II homozygous at the angiotensin converting enzyme (ACE) locus and AA homozygous at the angiotensin type I receptor (AT1R) locus had lower BP and a better lipid profile than the rest of the group. Thus, in this explorative study, we report an association between insulin sensitivity and a polymorphism at the alpha(2A)AR locus. We suggest the presence of gene-gene interactions in the renin-angiotensin system and the sympathetic nervous system.

Adult↗
PubMed2001

Plasma N-terminal pro-atrial natriuretic peptide predicts death after premature myocardial infarction, but not as well as radionuclide ejection fraction. A ten-year follow-up study.

OBJECTIVE: To assess N-terminal pro-atrial peptide (N-ANP) as a predictor of total and cardiac death in patients with previous premature myocardial infarction (MI). DESIGN: In this prospective cohort study, we measured plasma N-ANP by ELIZA assays and ejection fraction (EF) by radionuclide ventriculography in a cohort of 247 patients (193 men and 54 women) who had had MI at a relatively young age (males: first MI at age < or =55; females <60). RESULTS: After 10 years 44 patients had died, 36 from cardiac causes. After using a stepwise procedure to adjust for other prognostic factors (i.e. plasma total homocysteine (tHcy), C-reactive protein and age), the relative risk (RR) was 2.00 (95% confidence interval (CI) 1.05-3.80) (p = 0.03) for death of all causes and 2.32 (95% CI 1.19-4.55) (p=0.01) for cardiac death when the top quartile was compared to the three lower quartiles of N-ANP. When radionuclide EF entered the Cox model, N-ANP became insignificant as a predictor of mortality. CONCLUSION: N-ANP was a significant predictor of total death and cardiac death in young survivors of MI, but radionuclide EF was a more independent prognostic variable.

Adult↗
PubMed2001

Zinc potentiates the antiviral action of human IFN-alpha tenfold.

During the last decade, various zinc salts have been used against the common cold syndrome, which is known to be initiated by respiratory viruses, particularly rhinoviruses. Using rhinovirus as the challenge virus, we investigated whether zinc salts (Zn) could potentiate the antiviral action of native human leukocyte interferon (HuIFN-alpha) and rHuIFN-gamma. We found that HuIFN-alpha was potentiated tenfold at rather low levels of IFN activity (0.6-0.8 U/ml), resulting in 100% protection. Zn alone gave only marginal protection, if any. In contrast to HuIFN-alpha, rHuIFN-gamma directly increased the cytopathic effect of rhinovirus at low levels (<2 U/ml) but protected the cells at higher IFN levels (5-20 U/ml). No potentiation was seen with Zn. HuIFN-beta protected against rhinovirus at the same doses as used with HuIFN-alpha, but in contrast to HuIFN-alpha, no potentiation was noted.

Antiviral Agents↗
PubMed2001

Receiving help at home: the interplay of human and technological assistance.

OBJECTIVES: This research investigated use of mobility equipment as a substitute for human assistance and also examined whether use of mobility equipment results in out-of-pocket cost savings associated with formal home care services. METHODS: The authors analyzed data collected from 9,230 respondents to the Adult Followback Survey of the Disability Supplement to the 1994 and 1995 National Health Interview Survey (NHIS-D) who reported both mobility and limitations in daily living activities to test study hypotheses, using regression analyses to control for selection effects in mobility equipment use. RESULTS: Use of canes and crutches (but not walkers and wheelchairs) reduced both formal and informal hours of care received per week by sample members; there was also evidence of substitution on the individual activities of daily living task level. Use of canes and crutches was also associated with lower out-of-pocket costs for formal helping services. DISCUSSION: Findings suggest that canes and crutches are effective and efficient home care resources that have the potential to increase the autonomy of adults with disabilities and to facilitate chronic condition self-management.

Activities of Daily Living↗
PubMed2001

The accuracy of the ACSM stair-stepping equation.

PURPOSE: The purpose of this study was to determine the accuracy of the ACSM equation used to estimate the oxygen cost of stepping exercise. The equation appears as: VO2 (mL.kg(-1).min(-1)) = 0.2 (steps.min(-1)) + (step height, m x steps.min(-1) x 2.4) + 3.5. METHODS: Subjects were 55 men and women between the ages of 19 and 35 yr. Steady-state VO2 was measured at six different combinations of step heights and step rates. Step heights were 0.1, 0.2, and 0.3 m (4, 8, and 12 in, respectively) and step rates were 20 and 25 steps.min(-1). Predicted VO2 for each workload was derived from the ACSM equation. RESULTS: Mean differences between actual and predicted VO2 values ranged from -0.2 to -1.1 mL.kg(-1).min(-1) and was -0.6 mL.kg(-1).min(-1) for all workloads combined. All differences except the lowest were significant (P < or = 0.05). Total errors ranged from 1.3 to 2.5 mL.kg(-1).min(-1) and was 1.9 mL.kg(-1).min(-1) for all workloads combined. For all workloads combined, the correlation between actual and predicted VO2 was r = 0.95 with a SEE = 1.7 mL.kg(-1).min(-1). The statistics are comparable to other ACSM prediction equations. CONCLUSION: Although all of the mean differences except one were statistically significant, they were judged negligible from a practical standpoint. Therefore, it was concluded that the ACSM equation is an accurate predictor of the oxygen cost of stair-stepping exercise.

Adult↗
PubMed2001

Detection of mRNA for the terminal complement components C5, C6, C8 and C9 in human umbilical vein endothelial cells in vitro.

Human umbilical vein endothelial cells (HUVEC) have previously been shown to synthesize the functional terminal pathway of complement based on the detection by radioimmunoassay of the terminal complement complex (TCC) on coincubated agarose beads. In addition, C7 secretion by these cells in amounts comparable to C3, as well as C7 mRNA, has recently been demonstrated. However, it has not been possible to detect C5-6 and C8 in the fluid phase, and only trace amounts of soluble C9. Against this background we examined whether mRNA for the remaining terminal complement factors was present in HUVEC. By the use of reverse transcription (RT)-polymerase chain reaction (PCR) and Northern blot the presence of mRNA for complement factors C5, C6, C8 and C9 was demonstrated.

Base Sequence↗
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↗