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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 91 records · Page 5Linked to original sources

Why ruminators are poor problem solvers: clues from the phenomenology of dysphoric rumination.

The phenomenology of dysphoric rumination and its consequences for problem solving were explored in 3 studies. In Study 1, self-focused rumination, compared with distraction, led dysphoric participants to rate their own biggest problems as severe and unsolvable and to report a reduced likelihood of actually implementing their solutions. Clues into the mechanisms behind these findings were explored in Study 2. The results showed that dysphoric ruminative thought is characterized by a focus on personal problems combined with a negative tone, self-criticism, and self-blame for problems as well as reduced self-confidence, optimism, and perceived control. Finally, Study 3 revealed a direct relationship between the negatively biased content of ruminative thoughts and reduced willingness to solve one's problems. Implications of these findings for the consequences of self-focused rumination are discussed.

Adult↗

Different apoptotic pathways are induced from various intracellular sites by tetraphenylporphyrins and light.

The induction of apoptosis from different intracellular sites was studied by exposing V79 Chinese hamster fibroblasts to photodynamic therapy (PDT) with various porphyrins and light. The effects of two lipophilic, intracellular membrane-localized porphyrins, tetra(3-hydroxyphenyl)porphyrin (3THPP) and Photofrin, were compared with that of two sulphonated meso-tetraphenylporphines (TPPS2a and TPPS4), which are taken up into lysosomes by endocytosis. Apoptotic fractions induced by the various dyes and light were quantified by flow cytometry using the terminal deoxynucleotidyl transferase (TdT) assay. Cell fragmentation was measured in parallel, while the nuclear morphology of apoptotic cells was studied by fluorescence microscopy. Different kinetics were found for the induction of DNA strand breaks characteristic of apoptotic cells. PDT-induced damage to membranes resulted in an increasing number of apoptotic cells for about 12 h after PDT After damage to lysosomes, apoptotic cells were not detected until more than 12 h after PDT. Furthermore, apoptotic bodies were not observed after PDT-induced damage to intracellular membranes, whereas apoptosis induced from lysosomal sites was characterized by extensive cell fragmentation. Cell fragmentation occurred in combination with or in the absence of nuclear fragmentation. The results support the idea that the degradation phase of apoptosis can consist of a sequence of independent steps rather than a common final pathway.

Animals↗

The histology and immunohistochemistry of free buccal mucosa and full-skin grafts after exposure to urine.

OBJECTIVE: To investigate the histological and immunohistochemical behaviour of free buccal mucosa and full-skin grafts after exposure to urine. MATERIALS AND METHODS: A buccal mucosal graft and a full-skin graft were freely transferred into the bladder of 12 minipigs, after stripping the bladder mucosa. Endoscopic investigations were carried out 2 and 5 months after surgery, and the grafts examined after death at 7 months, both histologically and immunohistochemically. RESULTS: Shrinkage of the full-skin graft was apparent endoscopically in five cases. Of the nine full-skin grafts, four showed severe inflammatory reactions, two necrosis and two ulcerations. Conversely, the 10 buccal mucosal grafts had fewer pathological findings (three minimal inflammation and three with scars) and a pronounced similarity on immunohistochemistry. CONCLUSION: The buccal mucosal graft showed significantly fewer adverse histopathological findings after long-term exposure to urine than the full-skin graft and is therefore a preferable material for urethral reconstruction.

Animals↗

Cardiac metal contents after infusions of manganese. An experimental evaluation in the isolated rat heart.

RATIONALE AND OBJECTIVES: Manganese dipyridoxyl diphosphate (MnDPDP), a contrast agent for liver MRI, releases free Mn2+ in a graded manner. The aim of the study was to compare the effects of brief versus prolonged infusions of MnDPDP and manganese chloride (MnCl2) on cardiac function, metabolism, Mn accumulation, and tissue metal content. METHODS: Isolated perfused rat hearts received 1-minute or 10-minute infusions of MnDPDP (100 microM, 1000 microM) or of MnCl2 (10 microM, 100 microM). Physiologic indices were measured intermittently, and tissue high-energy phosphate compounds and Ca/Fe/Mg/Mn/Zn contents were measured after a standardized Mn washout. RESULTS: One-minute and 10-minute infusions induced, respectively, minor and marked depressions of contractile function and corresponding elevations in myocardial Mn content. MnCl2 was markedly more potent than MnDPDP. Ten-minute infusions of the highest concentration of MnDPDP and MnCl2 lowered tissue Mg and elevated tissue Ca (MnCl2), whereas high-energy phosphates were unaffected. CONCLUSIONS: Mn uptake after Mn infusion is strongly related to the duration, concentration, and dose of free Mn ions. Differences in Mn accumulation between MnDPDP and MnCl2 were more pronounced after the 10-minute infusion.

Animals↗

Postacute care following stroke or hip fracture: single services and combinations used by Medicare beneficiaries (1987-1992).

OBJECTIVE: To describe the use of postacute services alone or in combination following a hospitalization for a hip fracture or stroke by Medicare beneficiaries who were relatively well and living in the community prior to the index event. METHODS: Health-service use histories were constructed using Medicare claims. Patients in the study represented all subjects from a 1% sample of Medicare beneficiaries who were age 70 years or older at the time of the index hospitalization. RESULTS: From 1987 to 1992, the proportion of patients receiving any postacute care and those receiving combinations of care increased. For example, there was a doubling of the proportion of patients with either condition using sequences of rehabilitation with home health or SNF and home health. Within 1 year of the hospitalization, 42.6% of patients with stroke and 35.0% post-hip fracture had been rehospitalized. DISCUSSION: Resource use and assessment of patient outcomes should be examined across the continuum of postacute care and in the months beyond to examine the relative effectiveness of different combinations of care.

Aged↗

International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Standardization Project for the Measurement of Lipoprotein(a). Phase 2: selection and properties of a proposed secondary reference material for lipoprotein(a).

The International Federation of Clinical Chemistry and Laboratory Medicine Working Group for the Standardization of Lipoprotein(a) Assays has initiated a project to select a secondary reference material for lipoprotein(a) that can standardize the measurement of this lipoprotein. Most of the analytical problems with lipoprotein(a) assays are due to apolipoprotein(a) kringle 4 type 2 reactive antibodies and values being expressed in mg/l mass units rather than as nmol/l of apolipoprotein(a) particles. In Phase 2, four manufactured materials were compared for analytical performance, commutability properties and method harmonization in 27 lipoprotein(a) test systems. Results of precision and linearity testing were comparable for all materials whereas testing for the harmonization effect resulted in an among-assay coefficient of variation for corrected lipoprotein(a) values of between 11% and 22%. The material that gave maximum harmonization achieved a variation of < 8% for 18 immunonephelometric and immunoturbidimetric assay systems. It can be hypothesized that this residual variation in part takes into account the inaccuracy of lipoprotein(a) measurement due to apolipoprotein(a) size polymorphism. On the basis of acceptable analytical performance, maximal harmonization effect and documented stability, a lyophilized material has been selected as the common calibrator for lipoprotein(a) to be used in a value transfer procedure by diagnostic companies.

Evaluation Studies as Topic↗

Early induction of binucleated cells by ultraviolet A (UVA) radiation: a possible role of microfilaments.

The effects of UVA (365 nm) radiation on the cellular distribution of F-actin and formation of binucleated cells have been studied using 3T3 Swiss albino mouse fibroblasts and V79 Chinese hamster fibroblasts. Ultraviolet A at biologically relevant fluences was found to disintegrate the actin filaments in the cells shortly (5 min) after irradiation, concomitant with the formation of cells with two nuclei. In 76-100% of the bi- and multinucleated cells the distribution of F-actin was clearly altered. Cells in GI phase of the cell cycle were most probably involved in the formation of binucleated cells. The disintegration of F-actin was presumably not due to depolymerization of F-actin to G-actin, as the amount of F-actin in the cells was unaltered after UVA exposure but rather due to direct breakage of the actin filaments. Ultraviolet B (297/302 nm) had no effect on the cellular distribution of microfilaments, not even at highly lethal fluences.

3T3 Cells↗

The temperature dependence of protoporphyrin IX production in cells and tissues.

The formation of protoporphyrin IX (PpIX) in human skin during topical application of 5-aminolevulinic acid (ALA) was found to be strongly temperature dependent, with an activation energy of about 17 kcal/mol. This temperature dependence is mainly related to porphyrin production and not to ALA penetration into the skin. The penetration of ALA into mouse and human skin was almost temperature independent. The activation energy of PpIX production in mouse skin was practically identical with that in human skin. The activation energy of ALA uptake by cells in vitro was about 10 kcal/mol and that for PpIX production was about 13 kcal/mol. The latter activation energy was within the error limits similar to that for the activity of the enzyme porphobilinogen deaminase, suggesting that this enzyme might represent a rate-limiting step for PpIX production in living tissue.

Administration, Topical↗

Altered serum concentrations of TGF-beta 1 and Lp(a) lipoprotein and their correlation in patients with first acute myocardial infarction.

BACKGROUND AND AIM: The association between high plasma Lp(a) lipoprotein and coronary heart disease has been confirmed in numerous case/control and prospective studies. A high Lp(a) level has also been shown to be an independent genetic risk factor, while its inverse relationship with TGF-beta 1 has suggested that it may interfere with plasmin-mediated activation of TGF-beta 1 and result in increased endothelial activation, as well as migration and proliferation of vascular smooth muscle cells. The aim of this study was to evaluate Lp(a) and TGF-beta 1 and their interactions in patients with first acute myocardial infarction (AMI). METHODS AND RESULTS: A total of 107 patients with first AMI and 103 age and sex-matched controls were studied. Very good agreement was found between QEI and RIA determinations of Lp(a) (p < 0.0001). Lp(a) levels were significantly elevated in cases (QEI: p < 0.031; RIA p < 0.002 respectively). Division by gender gave statistically significant differences in females only. Plasma levels of the active form of TGF-beta 1 were decreased in cases, though significantly (p < 0.029) in males only. CONCLUSIONS: Serum concentrations of Lp(a) and TGF-beta 1 are significantly altered in AMI patients. The differences are gender-dependent: Lp(a) is higher in females, and TGF-beta 1 is lower in males. Increased Lp(a) levels are accompanied by decreased active TGF-beta 1 levels and this inverse correlation is statistically significant (p < 0.001).

Aged↗

Intracellular metabolism of a 2'-O-methyl-stabilized ribozyme after uptake by DOTAP transfection or asfree ribozyme. A study by capillary electrophoresis.

The uptake and cellular metabolism of a fluorescein-labelled synthetic ribozyme stabilized by 2'- O -methyl modification and a 3' inverted thymidine have been studied, employing capillary gel electrophoresis as a novel and efficient analytical method. After internalization by DOTAP transfection, electrophoretic peaks of intact ribozyme and different degradation products were easily resolved and the amount of intracellular intact ribozyme was quantified to >10(7) molecules/cell at the peak value after 4 h transfection. On further incubation the amount of intracellular intact ribozyme decreased due to both degradation and efflux from the cell. However, even after 48 h incubation there were still >10(6) intact ribozyme molecules/cell. Clear differences both in uptake and in metabolism were seen when comparing DOTAP transfection with the uptake of free ribozyme. Fluorescence microscopy studies indicated that the ribozyme was mainly localized in intracellular granules, probably not accessible to target mRNA. This implies that agents able to release the intact ribozyme from intracellular vesicles into the cytosol should have a considerable potential for increasing the biological effects of synthetic ribozymes.

Base Sequence↗

Permanent Committee of the International Congress of Human Genetics.

For over three decades, the Permanent Committee of the International Congresses of Human Genetics has served the purpose of selecting a host and site for the quadrennial Congress, which is due next in 2001. The Committee has statutes and consists of one voting representative from 38 nations and other ex officio members, much like the General Assembly of the United Nations. It meets twice during each International Congress, otherwise conducting its business by mail and telecommunication. Its structure could be the beginnings of a truly global democratic body of human geneticists to address other issues and to serve other purposes, as human genetics becomes increasingly international, as inevitably it must.

Congresses as Topic↗

[Molecular biology in the diagnosis of cardiovascular diseases].

Genes shown to affect risk factors or protective factors with respect to coronary heart disease (CHD) have been identified at the APOB, APOAI, LPA, LDLR, APOE and CETP loci. Rare mutations (e.g., in the LDLR and APOE genes) may have a major effect, whereas genes belonging to normal polymorphism have only a moderate effect. Even genes with only a slight effect can be clinically important in combination with other genes or life-style factors. There is gene to gene interaction between LDLR and APOE genes. Important risk factors determined by genes as well as by environmental factors are homocystein and fibrinogen. In addition to traditional lipid and apoprotein measurements, the levels of Lp(a) lipoprotein, fibrinogen and homocystein should be examined in connection with diagnosing CHD cases. DNA analyses are appropriate when familial hypercholesterolemia is suspected, and it is likely that the importance of mutation analyses will increase significantly in the near future.

Biomarkers↗

Beta-thromboglobulin in urine and plasma: influence of coronary risk factors.

Blood platelet activation in vivo was evaluated by measuring beta-thromboglobulin in plasma and high molecular weight beta-thromboglobulin in urine in hypertensive smoking and nonsmoking middle-aged men (n=36) and in normotensive age-matched controls (n=40). We found no significant linear relationships between nocturnal or resting urinary high molecular weight beta-thromboglobulin and plasma beta-thromboglobulin in the combined hypertensive and normotensive groups. The excretion of high molecular weight beta-thromboglobulin correlated significantly with diastolic blood pressure when all subjects were pooled. After 60 minutes supine rest, nonsmokers had higher excretion of high molecular weight beta-thromboglobulin than smokers. Plasma beta-thromboglobulin levels tended to be higher in hypertensives. In multivariate analyses, resting high molecular weight beta-thromboglobulin excretion was positively related to diastolic blood pressure and negatively related to smoking, whereas plasma beta-thromboglobulin was positively related to diastolic blood pressure and inversely related to apolipoprotein A1 and B. We conclude that urinary high molecular weight beta-thromboglobulin and plasma beta-thromboglobulin are not closely related, but are complementary analyses, as there are methodological confounders for both variables.

Adult↗

[Molecular biology diagnostics of hereditary metabolic diseases].

Metabolic diseases are often a result of monogenic inheritance and are suitable subjects for molecular diagnosis. Much progress has been made on research into this group of diseases, and further advances are expected after the completion of the Human Genome Project (HUGO) and as a consequence of improved molecular genetic methods. Although it is possible to diagnose many metabolic disorders by biochemical analyses of enzyme function, the underlying molecular genetic defects must be identified in order to be able to make accurate diagnoses of patients and their relatives. A molecular diagnosis is also a pre-condition for gene therapy. It is of paramount importance that more knowledge is gained of the correlation between genotype and phenotype for the genetic counselling of patients and their families. Important challenges at the present time are how to achieve a better understanding of the molecular and metabolic basis for the way in which diseases manifest themselves clinically and the factors which modify the phenotype.

DNA Mutational Analysis↗

Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S)

BACKGROUND: The Scandinavian Simvastatin Survival Study (4S) randomized 4444 patients with coronary heart disease (CHD) and serum cholesterol 5.5 to 8.0 mmol/L (213 to 310 mg/dL) with triglycerides < or =2.5 mmol/L (220 mg/dL) to simvastatin 20 to 40 mg or placebo once daily. Over the median follow-up period of 5.4 years, one or more major coronary events (MCEs) occurred in 622 (28%) of the 2223 patients in the placebo group and 431 (19%) of the 2221 patients in the simvastatin group (34% risk reduction, P<.00001). Simvastatin produced substantial changes in several lipoprotein components, which we have attempted to relate to the beneficial effects observed. METHODS AND RESULTS: The Cox proportional hazards model was used to assess the relationship between lipid values (baseline, year 1, and percent change from baseline at year 1) and MCEs. The reduction in MCEs within the simvastatin group was highly correlated with on-treatment levels and changes from baseline in total and LDL cholesterol, apolipoprotein B, and less so with HDL cholesterol, but there was no clear relationship with triglycerides. We estimate that each additional 1% reduction in LDL cholesterol reduces MCE risk by 1.7% (95% CI, 1.0% to 2.4%; P<.00001). CONCLUSIONS: These analyses suggest that the beneficial effect of simvastatin in individual patients in 4S was determined mainly by the magnitude of the change in LDL cholesterol, and they are consistent with current guidelines that emphasize aggressive reduction of this lipid in CHD patients.

Adult↗

[Use of 5-aminolevulinic acid in photochemotherapy and fluorescence diagnostics].

5-aminolevulinic acid is an early intermediate product in the synthesis of heme. Some of the enzymes in the heme synthesis chain have altered activities in tumor tissue, so that application of 5-aminolevulinic acid leads to an accumulation of protoporphyrin IX in tumors. This molecule absorbs light and acts as a potent photosensitizer; tumors containing the compound can therefore be destroyed by light. 5-aminolevulinic acid based photochemotherapy is presently being employed in the treatment of thin basal cell carcinomas in many countries. The cosmetic result of this treatment is excellent. Furthermore, it is a simple and inexpensive form of treatment with curative rates comparable to those of established therapy modalities. Experimentally, a number of other malignant lesions reachable by light via optical fibers are being treated. Since protoporphyrin IX has a characteristic red fluorescence, 5-aminolevulinic acid can also be applied for diagnostic purposes.

Aminolevulinic Acid↗

Apoptosis induction by different pathways with methylene blue derivative and light from mitochondrial sites in V79 cells.

The importance of mitochondria for the induction of apoptosis by photodynamic therapy (PDT) was studied with a new photosensitizing dye, methylene blue derivative (MBD), and light. By using fluorescence microscopy and by measuring the MBD-PDT-induced inhibition of specifically subcellularly localized marker enzymes, we show that MBD is localized in mitochondria and not in lysosomes, endoplasmic reticulum or Golgi apparatus of V79 Chinese hamster fibroblasts. Cellular uptake kinetics and fluorescence properties of the dye in cells were characterized. Cell death was studied by a cell survival assay and by flow cytometry of cells stained using the terminal deoxynucleotidyl transferase (TdT) assay. MBD with light induced cell death by apoptosis via 2 different pathways, one rapid and one delayed, depending on the amount of dye in the cells. Cells treated with an MBD concentration higher than 0.05 microg/ml died by apoptosis within 3 hr after light exposure. At a concentration of 0.05 microg/ml MBD, cell death was induced slowly, and apoptotic cells appeared increasingly from the second day after PDT. Combination studies with 2-deoxyglucose (2-DOG) and carbonylcyanide-m-chlorophenylhydrazone (CCCP), inhibitors of glycolysis and oxidative phosphorylation, respectively, indicated that MBD and light inhibited mitochondrial oxidative phosphorylation. Abolishment of both energy sources led to cell death by necrosis within 6 hr. Inhibition of glycolysis alone induced apoptosis between 3 and 6 hr, while inhibition of mitochondrial oxidative phosphorylation alone led to delayed apoptosis within days.

Animals↗

Verapamil enhances the uptake and the photocytotoxic effect of PII, but not that of tetra(4-sulfonatophenyl)porphine.

The influence of the calcium channel blocker verapamil on the sensitivity of mouse fibrosarcoma cells of the line EMT-6 to treatment with Photofrin II (PII) or tetra(4-sulfonatophenyl)porphine (TPPS4) and light has been assessed. Cells were treated with 1.5 microg/ml PII or 75 microg/ml TPPS4 overnight in the absence or presence of 50 microg/ml verapamil and subsequently exposed to light. Verapamil increased the sensitivity of the EMT-6 cells to PII-induced photoinactivation by a factor of 2. In contrast, verapamil decreased the sensitivity of the cells to TPPS4-induced photoinactivation by 50-60%. Both sensitizers were found to be located to a large extent in lysosomes as revealed by fluorescence microscopy and by photochemical inactivation of the lysosomal marker enzyme beta-N-acetyl-D-glucosaminidase. Verapamil increased the uptake of PII by 30% and reduced the uptake of TPPS4 by 20%. Furthermore, verapamil enhanced the binding and uptake of LDL by about 40%. In conclusion, the effects of verapamil-induced sensitization of EMT-6 cells treated with PII or TPPS4 and light can to a large extent be attributed to the modulatory effects of verapamil on endocytosis.

Animals↗