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Biomedical subjects

K Berg

Publications and source records attributed to K Berg.

At least 181 records · Page 10Linked to original sources

[Life threatening anaphylaxis after repeated cisplatin administration: case report and neu therapy concepts].

The present case reports of a 58-year-old female patient presenting with severe (III degrees) anaphylactic reaction due to repeated chemotherapy with Cisplatin. After resection of the advanced ovarian carcinoma the patient was presented with complaints of itching, angioneurotic edema and dyspnea in 1990 when Cisplatin had been infused for the first time. Due to relapse after four years a further operation was performed and as much of the tumour as possible was resected. Then again, Cisplatin was applied. Cortisone, H1- and H2-blockers were given prior to its application increasing the tolerance of treatment. Subsequent treatment with further Cisplatin infusion, however, resulted in severe anaphylactic shock with dyspnea and cold sweat. Emergency treatment included application of pure oxygen, two large i.v. cannulas, and 1.5 l of crystalloid, and 0.5 l of colloids (Gelafundin). Additionally, a potent vasoconstrictor (Akrinor) and 750 mg Methylprednisolone were given. Symptoms improved as blood pressure normalised, and the patient felt much better 20 minutes later. In summary, the present case report proves that anaphylactic shock induced by Cisplatin demands interdisciplinary action. This particularly applies to the interval between occurrence of the first shock signs and arrival of the emergency team.

Anaphylaxis↗

B cell differentiation factor-induced B cell maturation: regulation via reduction in cAMP.

We have previously described a novel human B cell differentiation factor (BCDF), 446-BCDF, that is distinct biochemically and functionally from other cytokines. Since signal transduction pathways involved in human B cell differentiation have been incompletely studied and are poorly understood, we assessed the effects of 446-BCDF on various intracellular second messenger systems. After exposure of B cells to 446-BCDF, intracellular cAMP concentration started to decrease at 5 min and was significantly lower at 30 min and reached the lowest level at 4 hr. In most cases, cAMP concentrations returned toward baseline by 24 hr. A cAMP analog (dibutyryl cAMP), a stimulator of adenyl cyclase (forskolin), and phosphodiesterase inhibitors (aminophylline and IBMX) which inhibited the 446-BCDF-induced decrease in intracellular cAMP, inhibited 446-BCDF-induced B cell differentiation, suggesting that the fall in intracellular cAMP was a critical event in this process. To understand the mechanism involved in the reduction of cAMP, B cells were treated with pertussis toxin (PTX), a Gi protein inhibitor. Pertussis toxin blocked 446-BCDF-induced B cell differentiation as well, suggesting that 446-BCDF may function by stimulation of a Gi-linked receptor resulting in the inhibition of adenylate cyclase with a consequent reduction in cAMP. Other cytokines known to promote Ig secretion (IL2 and IL6) also caused a reduction in cAMP, suggesting that this pathway may be generally important in B cell differentiation. Taken together, these data suggest that at least one pathway of terminal maturation in B cells may involve the reduction of intracellular cAMP.

Adenylate Cyclase Toxin↗

The influence of the cysteine protease inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanidio)butane (E64) on photobiological effects of tetra(4-sulfonatophenyl)porphine.

Human cervix carcinoma cells of the line NHIK 3025 were exposed to light after 18 h incubation with tetra(4-sulfonatophenyl)porphine (TPPS4) in the absence or presence of the cysteine protease inhibitor L-trans-epoxysuccinyl-leucyl amido(4-guanidino)butane (E64) followed by 1 h in sensitizer-free medium. E64 changed the photochemical properties of TPPS4 in NHIK 3025 cells, i.e., TPPS4 fluorescence yield was enhanced 2.5-fold and photochemically induced lysosomal rupture and loss of cell bound TPPS4 were inhibited. Additionally, E64 slightly (10%) reduced the sensitivity of the NHIK 3025 cells to photoinactivation. This is not likely to be due to its inhibitory effect on protease activity, but correlates with its inhibition of lysosomal rupture. The present results indicate that the release of lysosomal cysteine proteases from the lysosomal compartments are of little or no importance in the photochemical inactivation of NHIK 3025 cells when TPPS4 is used as photosensitizer.

Carcinoma in Situ↗

Molecular cloning and characterization of the filarial LIM domain proteins AvL3-1 and OvL3-1.

A full-length cDNA of the filarial nematode Acanthocheilonema viteae was isolated from a cDNA library of female worms, using a partial cDNA of the OvL3-1 gene of Onchocerca volvulus as a probe. The AvL3-1 cDNA contained an open reading frame which encoded for a protein with a theoretical molecular weight of 64 kDa. The deduced protein contained a predicted signal sequence, a short repetitive motive of unknown function, and three LIM domains. The structure of the LIM domains was identical to those of zyxin, a cytoskeleton-associated protein of chicken fibroblasts, suggesting that AvL3-1 has a similar role in filarial nematodes. The sequence information was used to isolate the homologous cDNA of O. volvulus by PCR from a cDNA library of female O. volvulus, which showed an overall identity of 76.9% to AvL3-1 on the protein level. AvL3-1 was expressed in Escherichia coli and the affinity-purified fusion free protein was used to immunized jirds (Meriones unguiculatus). Immunization together with the adjuvant STP or with Freund's adjuvant induced IgG and IgM antibody responses, but no significant protection against a challenge infection with L3 of A. viteae, compared to appropriate control groups.

Amino Acid Sequence↗

Screening for known mutations in the LDL receptor gene causing familial hypercholesterolemia.

Familial hypercholesterolemia (FH) is caused by defective low density lipoprotein (LDL) receptors and is characterized by hypercholesterolemia and premature coronary heart disease. Two strategies can be used to identify the mutation in the LDL receptor gene underlying FH. One strategy is to search for novel mutations by DNA sequencing with or without prior mutation screening. The other strategy is to screen for known mutations. In this study we employed the latter strategy to screen 75 unrelated, Norwegian FH subjects for 38 known mutations. Three of the 38 mutations were detected in our group of FH subjects. Two subjects had FH-Padova, one had FH-Cincinnati-2 and one had FH-Gujerat. When additional unrelated FH heterozygotes were screened for the three mutations, the gene frequencies were 1.3%, 1.0% and 3.0%, respectively. In addition to identifying known mutations we also detected a novel stop codon in codon 541 (S541X). We conclude that screening for known mutations in the LDL receptor gene should be used as a complementary strategy to screening for novel mutations in order to understand the molecular genetics of FH.

Base Sequence↗

S phase arrest and induction of multinucleated cells after exposure to ultraviolet radiation.

The effects of UVA (365 nm) and UVB (297/302 nm) radiation on cellular proliferation, cell cycle progression, aneuploidy and multinucleus induction have been studied in two different fibroblast cell lines; V79 Chinese hamster lung fibroblasts and 3T3 Swiss albino mouse fibroblasts. UVA and UVB were found to inhibit proliferation of the cells in a fluence-dependent manner. This inhibition was due to a temporary accumulation of cells in the S phase of the cell cycle, as determined by flow cytometry of UV-irradiated V79 cells. The UVA- and UVB-induced S phase delay was observed a few hours after irradiation and by 48 h post-irradiation the cells had recovered from cell cycle arrest. For UVA, but not for UVB, the elongation of S phase was followed by a small accumulation of cells in the G2 phase. After exposure to UVA and a post-irradiation time long enough for the cells to recover from cell cycle arrest, a large proportion of the cells were polyploid, with two or more nuclei. Multinucleated cells were not, however, induced by UVB irradiation.

3T3 Cells↗

Cardiovascular responses to noxious stimuli during isoflurane anesthesia are minimally affected by anesthetic action in the brain.

We investigated the ability of isoflurane to ablate cardiovascular responses to a noxious stimulus (dew-claw clamp) in 10 goats during isoflurane delivery throughout the body and with selective delivery to either the head or torso. Whole-body minimum alveolar anesthetic concentration (MAC) and the concentration blocking autonomic responses (MAC-BAR) were determined. Next, cranial blood (jugular vein) was drained into an oxygenator and reinfused into the head (carotid artery). In six animals (Group I) isoflurane to the torso was maintained at 0.2%-0.3%, and the cranial isoflurane concentration adjusted to determined MAC-BAR; in three animals (Group II) cranial isoflurane was maintained at 0.2%-0.3%, and the end-tidal isoflurane adjusted to determine MAC-BAR. Whole-body MAC was 1.4% +/- 0.3%; whole-body MAC-BAR was 3.7% +/- 0.4%, a concentration range associated with hypotension (46 +/- 8 mm Hg). During bypass, MAC-BAR was 5.6% +/- 2.4% for Group I (P < 0.05) and 2.2% +/- 0.7% for Group II (P < 0.05). Changes in blood pressure, but not heart rate, correlated with the isoflurane concentration, both during the whole-body period and bypass period for Groups I and II. We conclude that isoflurane suppresses the arterial blood pressure response to noxious stimuli, but only with concomitant hypotension, and that the brain has little influence on this response, as its MAC-BAR substantially exceeded whole-body MAC-BAR.

Anesthetics, Inhalation↗

Effects of manganese dipyridoxyl diphosphate, dipyridoxyl diphosphate--, and manganese chloride on cardiac function. An experimental study in the Langendorff perfused rat heart.

RATIONALE AND OBJECTIVES: Manganese dipyridoxyl diphosphate (MnDPDP) is a promising contrast agent for magnetic resonance imaging of the liver. The authors explored the possibility that high concentrations of MnDPDP may cause manganese ion (Mn++)-induced side effects on cardiac function. METHODS: Potential cardiodepression by MnDPDP, DPDP--, and manganese chloride (MnCl2) (100-3,000 mumol/L) was investigated in the isolated rat heart, with left ventricular developed (systolic--end-diastolic) pressure and heart rate as the primary indices of cardiac function. RESULTS: During 5-minute exposures, 10% and 50% decreases in left ventricular developed pressure were observed for MnDPDP, 250 mumol/L and 1580 mumol/L; DPDP--, less than 100 mumol/L and 1000 mumol/L; MnCl2, 30 mumol/L and 250 mumol/L. Heart rate changes were not observed with MnDPDP. Cardiodepression was reversed within 2 minutes during a 14-minute recovery period for all investigated concentrations of MnDPDP and was less rapid for the highest concentrations of MnCl2. CONCLUSIONS: Manganese dipyridoxyl diphosphate is well tolerated in the rat heart at concentrations as high as 200 to 250 mumol/L and is approximately 10 times less cardiotoxic than MnCl2. Cardiodepressive effects of MnDPDP in the present rat heart model, perfused in the absence of blood and proteins, are related primarily to the release of free Mn++ ions and in part to the simultaneous release of DPDP--.

Animals↗

A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia.

Eight mutations in the gene (the RYR1 gene) encoding the calcium release channel of sarcoplasmic reticulum (SR) in skeletal muscle are so far known to be very closely linked to malignant hyperthermia susceptibility in man and are regarded to be causative. We have examined 41 Swedish families where malignant hyperthermia had occurred in at least one member during anaesthesia, with respect to three of the known mutations. The mutations were Arg163Cys; Ile403Met and Arg614Cys (also known as the "pig mutation"). In three (i.e. 7%) of the families we detected the Arg614Cys mutation, and this was the only one of the mutations searched for that was observed. This indicates that other mutations than those searched for in this study must cause malignant hyperthermia susceptibility in most Swedish malignant hyperthermia susceptible families.

Adult↗

Genetics in democratic societies--the Nordic perspective.

This report, with its emphasis on consensus points in the deliberations of the First Bioethics Workshop under the auspices of the Nordic Genome Initiative (an activity under the Nordic Council through its Nordic Programme Committee for Biotechnology), presents a Nordic perspective on the international discussion of ethical and legal issues relating to genetic testing. The Nordic countries have important common denominators with respect to political structure, education, religion, languages, cultural traditions and attitudes towards human values. A comprehensive national health service exists in all Nordic countries and there are important common legal foundations with great similarities between countries. However, in areas related to biotechnology there are considerable legal differences, but these differences do not necessarily reflect differences in underlying principles. Important ethical principles relevant to genetic testing that are shared by the Nordic countries include the concept of social justice with great stress on equality of treatment, the right to autonomy, the right to full disclosure of test results, strict confidentiality with respect to test results, the requirement that participation in testing programs must always be voluntary and based on information, and a responsible balance between risks or inconveniences on one hand and benefits on the other.

Abortion, Induced↗

A simple method to detect the RYR1 mutation G1021A, a cause of malignant hyperthermia susceptibility.

To search for the mutations RYR1 G1021A in families where malignant hyperthermia (MH) episodes have occurred, we have used an amplification-created restriction sites (ACRS) technique to detect the mutation. The previously described single-stranded conformation polymorphism (SSCP) technique was laborious and time consuming, but necessary to detect the mutation, whereas the method described here discriminates quickly and efficiently between homozygotes with the mutation, heterozygotes and homozygotes without the mutation.

Base Sequence↗

Medicare nursing home residents with a stroke. Characteristics and 90-day outcomes of care.

The objective of this article is to describe the characteristics and outcomes of Medicare patients admitted to nursing homes with a primary diagnosis of stroke. This study used longitudinal clinical information prospectively collected in National Health Corporation (NHC) nursing homes on admission and at discharge or death. In total, 2,345 residents met the following study criteria: age 40 and over, newly admitted from a general hospital to a NHC home under Medicare, and previously living in the community. The outcomes were functional status and discharge disposition within 90 days. By 90-days postadmission, 27.4% remained in the nursing home, 22.4% had gone home, 25.7% had been readmitted to a general hospital, 8.7% had entered another facility, and 15.6% of the patients with stroke had died. Residents who went home showed the greatest improvement in functional status in Barthel Index scores, from 35.2 (SD21.1) to 47 (SD 25.6); 20% were totally dependent and only 34% scored above 60 on the index. Further study is needed to examine the functional outcomes of stroke survivors over the longer term and compare the relative effectiveness of nursing home interventions with other postacute care options.

Activities of Daily Living↗

Serum Lp(a) lipoprotein levels in patients with coronary artery disease and the influence of long-term n-3 fatty acid supplementation.

The serum levels of Lp(a) lipoprotein (Lp(a)) were determined preoperatively in 601 patients with coronary artery disease, undergoing bypass operations. Compared with a reference group of 99 apparently healthy individuals, the Lp(a) levels were higher in the patient group (7.7 mg dl-1 vs. 5.1 mg dl-1, p = 0.012). In the patient group, there was a weak, but significant negative correlation between the Lp(a) levels and age (r = -0.10, p = 0.017), and in both groups the women had higher Lp(a) levels than the men. In the patients we found no significant correlations between Lp(a) and other serum lipids or lipoproteins, nor between Lp(a) and variables in the fibrinolytic system. We investigated the long-term effects of supplementation with n-3 polyunsaturated fatty acids (n-3 PUFAs) on the Lp(a) concentrations. Postoperatively, in a randomized fashion, 280 of the patients received 4 g of an n-3 PUFA concentrate (containing > 85% of long-chain n-3 PUFAs) per day, whereas 269 patients comprised the control group. The fatty acids in serum phospholipids were monitored, and a significant increase in the phospholipid n-3 fatty acids was noted in the n-3 PUFA group, as opposed to the virtually unchanged amounts in the control group. The Lp(a) levels were determined again after 6 months, and, compared with the control group, n-3 PUFA supplementation had no overall effect on the serum Lp(a) levels.

Adult↗

Association studies of estrogen receptor polymorphisms in a Norwegian testicular cancer population.

To examine a possible influence of estrogen receptor variants on the genetic susceptibility to germ cell cancer we have analyzed the allelic frequencies of three polymorphisms within the estrogen receptor gene in testicular cancer (n = 454) and control populations (n = 672). There were no differences in allelic frequencies in cancer patients compared to controls. Subgroup analyses did not indicate differences in allele frequencies for any of the polymorphisms in those individuals most likely to be predisposed to testicular cancer (patients with a history of maldescent of testicles and/or infertility, patients suffering from bilateral testicular cancer, and patients with familial testicular cancer). The data do not indicate that variation in the 5' end of the estrogen receptor gene confers susceptibility to testicular cancer.

Adolescent↗

Combined treatment of ionizing radiation and photosensitization by 5-aminolevulinic acid-induced protoporphyrin IX.

The response of human colon adenocarcinoma cells of the line WiDr to the combined treatment of ionizing radiation and photosensitization by 5-aminolevulinic acid-induced protoporphyrin IX was assessed by a colony-forming assay. A dose of X rays inactivating approximately 50% of the cells was used. Seventy to 85% of the cells accumulated in S and G2 + M phase 12-24 h after such a treatment as measured by flow cytometry, while the distribution of cells in the phases of the cell cycle approached that of untreated cells 48 h after X-ray treatment. Cellular photosensitization was developed by endogenous synthesis of protoporphyrin IX (PPIX) from the precursor 5-aminolevulinic acid (5-ALA). This was performed by treating the cells with 1 mM 5-ALA for 4 h in a serum-free medium. The endogenous synthesis of PPIX increased with time after the cells had been subcultured, i.e. the ability of the cells to synthesize PPIX increased 1.5-2-fold within 48 h of incubation. This was not due to effects of trypsin on the cells. Photochemotherapy with 5-ALA was given 0-48 h after X rays. The combined cytotoxic effect was analyzed by an isobologram after correction of the survival curves for microcolony formation and differences in intracellular concentration of PPIX. The results indicate that 5-ALA PCT given 0-4 h after X rays acts slightly antagonistically while 5-ALA PCT given 12-48 h after X rays acts slightly synergistically.

Adenocarcinoma↗