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Biomedical subjects

T Fischer

Publications and source records attributed to T Fischer.

At least 181 records · Page 10Linked to original sources
PubMed1996

Induction of interferon regulatory factors 2'-5' oligoadenylate synthetase, P68 kinase and RNase L in chronic myelogenous leukaemia cells and its relationship to clinical responsiveness.

The genes crucially determining the therapeutic response of chronic myelogenous leukaemia (CML) to interferon-alpha (IFN-alpha) are unknown. Recently, two independent IFN-alpha signalling pathways were identified: the classic pathway mediates induction of 2'-5' oligoadenylate synthetase (2-5 OAS), p68 kinase and IFN regulatory factor-2 (IRF-2), whereas the alternate pathway leads to activation of IFN regulatory factor-1 (IRF-1). We investigated whether deficient or imbalanced expression of components of these two pathways is associated with resistance of CML cells to antiproliferative action of IFN alpha/beta. Constitutive and IFN-induced transcript levels of IFN-dependent genes in mononuclear cells, granulocytes, monocytes, lymphocytes and CD34+ cells of chronic-phase CML and blast crisis patients were assessed by Northern blot techniques and were correlated with subsequent clinical responses to IFN therapy. Our results demonstrated that IFN-alpha or -beta treatment in vitro and in vivo leads to an enhanced expression of IRF-1, IRF-2. RNase L, p68 and 2-5 OAS which was independent of the degree of cellular differentiation and clonal evolution of CML. Neither the magnitude of induction of these genes nor the IRF-1/IRF-2 mRNA balance differed between chronic-phase CML patients responding or failing IFN-alpha therapy. These results indicate that failure of IFN-alpha treatment is not due to defects in mRNA induction of the above-mentioned candidate genes for the direct antiproliferative response to IFN type I.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

Sensitizing and irritant properties of 3 environmental classes of diesel oil and their indicator dyes.

3 dyes, Solvent Yellow 124 and Solvent Blue 79 or Solvent Blue 98, were added to diesel oils in Sweden for identification of their particular use and taxation bracket in late 1993. Health concern regarding the toxicity of the dyes resulted in several reports to the Worker Inspection Bureau. 36 men reporting skin disease supposedly caused by dyes were diagnosed to have irritant reactions, irritant contact dermatitis or exacerbation of other skin disease. Tests on 15 individuals from this group, and 20 healthy volunteers, failed to demonstrate contact allergy or contact urticaria to the dyes or dyed diesel oil. Patch tests with dyes (10% v/v) in pet. did not cause irritation. Tests of irritant properties of the diesel oils showed that the old type of oil, with high viscosity, high content or aromatic compounds and moderately high sulfur content, caused little irritation, whereas newer, lighter qualities of diesel oil, with low concentrations of aromatic compounds and low sulfur content, which cause less pollution to the environment when burnt, were significantly more irritant to the skin and probably a cause of the skin problems.

Adult↗
PubMed1996

Guidelines for measurement of skin colour and erythema. A report from the Standardization Group of the European Society of Contact Dermatitis.

This report reviews individual-related variables (age, sex, race, anatomical site, skin surface properties), intra- and interindividual variation (temporal, physical and mental activity, orthostatic effect, menstrual cycle/menopause), environment-related variables (light conditions, temperature) and various instrument-related variables that influence skin colour. CIE colorimetry (Minolta Chroma Meter) and spectrophotometric measurement (Derma Spectrometer) are considered. The guidelines give recommendations for measuring conditions and procedures.

Adult↗
PubMed1996

Repair of the distal biceps tendon using suture anchors and an anterior approach.

The authors describe a technique for repair of the biceps tendon rupture from the radial tuberosity. A single anterior incision, limited volar dissection, and implantable bone anchors were used. With this technique, the authors have repaired the distal biceps tendon in 5 men (mean age, 39 years). Four patients were laborers and 1 was an athlete. Mechanism of injury was a single traumatic event with an unanticipated large load being applied to the flexed arm. Four patients were treated acutely and 1 was treated 6 months after injury. All patients returned to preinjury activity levels by 5 months after repair of the tendon. Clinically, all repairs remained intact (mean followup, 2.5 years). Range of motion was symmetric. No evidence of associated nerve injuries, heterotopic bone formation, or olecranon tenderness occurred. Subjective, as well as objective, results were excellent in those 5 patients whose distal biceps tendon was repaired by the single volar incision and implantable anchors.

Adult↗
PubMed1996

Fragrance contact dermatitis: a worldwide multicenter investigation (Part I).

OBJECTIVE: The aim of this study was to determine the prevalence of responses to selected fragrance materials in patients with suspect fragrance allergy and to evaluate risk factors and associations with such responses. The validity of using specific fragrance ingredients versus a mixture of fragrances was evaluated in terms of predicting allergy to different fragrance ingredients. METHODS: One hundred sixty-seven subjects were evaluated in seven centers worldwide with a fragrance mix, the eight ingredients in the fragrance mixture, six other well-known fragrance allergens, balsam of Peru, and 15 lesser studied fragrance materials. RESULTS: The age of the patients was 44.9 +/- 17.5 years (mean +/- SD). More than 85% were women. A relatively high proportion gave a past history of atopic disease. Facial eruptions (40%) and hand involvement (26.7%) were the most common topographic sites. All but 4 of the 35 fragrance materials produced a positive response in > 1%. A reaction to fragrance mix occurred in 47.3%. Seven of the 34 ingredients tested produced an allergic response in more than 10% of those tested. Men were more likely than women to exhibit a positive response to five fragrance ingredients. White persons were more likely to react to perfume mix (52.8% versus 25.3%) and certain ingredients in the mix than Asian persons. Allergy to benzyl salicylate was more common in Japan than in Europe or the United States. CONCLUSION: The age at which patients with perfume allergy present for evaluation is similar to that of other contactants. Atopic individuals may be overrepresented in this group of patients. Face involvement is likely. White persons are more likely to react to fragrance mix, whereas in Asian patients benzyl salicylate was a more frequent allergen. Fragrance mix corrected with 85.6% of positive responses to fragrance ingredients. The addition of ylang ylang oil, narcissus oil, and sandalwood oil to fragrance mix would be expected to pick up 94.2% with positive responses to fragrance materials; adding balsam of Peru increases this to 96%.

Adult↗
PubMed1996

Overexpression of mouse p140 subunit of replication factor C accelerates cellular proliferation.

Screening of a murine cDNA expression library with an IFN-stimulated response element (ISRE), as a recognition site DNA probe, resulted in the isolation of a cDNA encoding a polypeptide of 1145 amino acids designated ISRE-binding factor-1. This was subsequently shown to be identical to the M(r) 140,000 subunit of replication factor C (RFC). RFC is required, along with the proliferating cell nuclear antigen and DNA polymerase delta, for the synthesis of the leading strand during DNA replication. RFC exhibits a structure-specific DNA-binding activity that has been localized to its M(r) 140,000 subunit (p140). Sequence-specific binding of this polypeptide to the ISRE occurs only with low affinity. Based on DNA-binding activity of the truncated RFC-p140 encoded by the partial cDNA isolated, the DNA-binding domain of this polypeptide was mapped to a region encoded by amino acids 366 to 540. Transfection of NIH 3T3 cells with an expression plasmid containing murine RFC-p140 driven by cytomegalovirus early promoter led to the establishment of stable cell lines that expressed a 2.5- to 3.0-fold higher RFC-p140 protein level in comparison with control cells. The stable clones exhibited significantly accelerated cell proliferation, indicating that RFC-p140 is the limiting subunit of an active RFC complex in normal cells.

3T3 Cells↗
PubMed1996

[Relationship between properties of 131I therapy and radioiodine kinetics].

AIM: The reason of unreproducible data under diagnosis and therapy with radioiodine should be elucidated. METHODS: The iodine content of the capsules was tested by a colorimetric method and by activation analysis. Radiochemical purity was determined by HPLC and by electrophoresis. Solubility of the capsules was investigated under different conditions. RESULTS: The iodine content of the capsules varied between 0.8 and appr. 100 micrograms/capsule. The radiochemical purity of the capsule iodine varied between 75% and 99.5% (main contamination: iodate). The solubility of the capsules differed. CONCLUSION: Additional non-radioactive iodine in the therapy capsules could be one reason of the reduced radioiodine-uptake under therapy.

Capsules↗
PubMed1995

Prolonged elevation of intracellular cyclic AMP levels in U937 cells increases the number of receptors for and the responses to formylmethionyl-leucylphenylalanine, independently of the differentiation process.

The effects of elevated levels of cyclic AMP induced by cholera toxin (CTx) were investigated on the differentiated promyelomonocytic cell line U937. After CTx treatment, the initial inhibition of the oxidative burst induced by N-formylmethionyl-leucyl-phenylalanine (FMLP) was followed by a progressive increase over 20 h, resulting in 4-6-fold potentiation of the initial burst. Various cyclic-AMP-elevating agents produced similar potentiation of the FMLP- or C5a-induced oxidative burst, but the phorbol 12-myristate 13-acetate-induced oxidative burst was not affected by CTx pretreatment of cells. Furthermore, the increase in arachidonate release and intracellular Ca2+ triggered by FMLP were amplified after CTx treatment. ADP-ribosylation of Gi alpha subunits catalysed by pertussis toxin was slightly increased after CTx treatment, despite similar immunoreactivity of the alpha subunit of Gi2. FMLP binding sites present in CTx-treated membranes were 3-6 times more abundant than in control membranes. Expression of mRNAs encoding the FMLP receptor and one of its related receptors were enhanced after CTx treatment of both undifferentiated and undifferentiated U937 cells. In parallel, after undifferentiated cells were treated with CTx, they were able to increase intracellular Ca2+, but not the oxidative burst, in response to FMLP. These data demonstrate that CTx, by increasing cyclic AMP, enhances the expression of chemotactic receptors independently of U937 cell differentiation.

Amino Acid Sequence↗
PubMed1995

IL-1 stimulates a diverging signaling pathway in EL4 6.1 thymoma cells. IL-2 release, but not IL-2 receptor expression, is sensitive to pertussis toxin.

We reassessed the involvement of Bordetella pertussis toxin (PTX)-sensitive proteins in the IL-1 signaling pathway on the responses induced by IL-1 on the murine thymoma cell line EL4 6.1. We demonstrate that the ADP-ribosyltransferase activity of PTX, and not its cell-anchoring B oligomer part, is responsible for the inhibition of IL-1-induced IL-2 release, since 1) the concentration of PTX (< or = 1 ng/ml) required to block the secretion is 100 to 1000 times lower than the concentration needed with the B oligomer; and 2) the mutated PT-9K/129G, devoid of ADP-ribosyltransferase activity, was inactive at 100 ng/ml. We found that partial ADP-ribosylation of the Gi2/Gi3 proteins before stimulation with IL-1 was sufficient to obtain full inhibition of IL-2 release. PTX did not however inhibit the appearance on the cell surface of the high affinity IL-2 receptors or the IL-2 release induced by PMA. In addition, we show that PTX prevented the expression of the IL-2 mRNA induced by IL-1, without affecting the binding of IL-2 specific nuclear factors to the T cell distal element of the IL-2 promoter. Furthermore, PTX also inhibited IL-1-induced proliferation of non-transformed thymocytes. In conclusion, our results demonstrate that IL-1-induced IL-2 release is sensitive to PTX-catalyzed ADP-ribosylation and that IL-1 activates a diverging pathway on EL4 6.1 cells.

Animals↗
PubMed1995

PDGF-BB, IGF-I and mechanical load stimulate DNA synthesis in avian tendon fibroblasts in vitro.

Resident cells in the surface epitenon and internal compartment of flexor tendons are subjected to cyclic mechanical load as muscle contracts to move limbs or digits. Tendons are largely tensile load bearing tissues and are highly matrix intensive with nondividing cells providing maintenance functions. However, when an injury occurs, tendon cells are stimulated to divide by activated endogenous growth factors and those from platelets and plasma. We hypothesize that tendon cells detect mechanical load signals but do not interpret such signals as mitogenic unless an active growth factor is present. We have used an in vitro mechanical load model, application of cyclic strain to cells cultured on flexible bottomed culture plates, to test the hypothesis that tendon cells require platelet-derived growth factor (PDGF-BB) and insulin-like growth factor-I (IGF-I) in addition to mechanical load to stimulate DNA synthesis. In addition, we demonstrate that in avian tendon cells, load and growth factors stimulate phosphorylation of tyrosine residues in multiple proteins, including pp60src, a protein kinase that phosphorylates receptor protein tyrosine kinases. A lack of mitogenic responsiveness to mechanical load alone by tendon cells may be a characteristic of a regulatory pathway that modulates cell division.

Animals↗
PubMed1995

Ear piercing, and nickel and cobalt sensitization, in 520 young Swedish men doing compulsory military service.

Piercing the earlobes has increased in popularity among males in recent years. This habit would be expected to increase the incidence of nickel and cobalt sensitization. Patch testing with nickel sulfate and cobalt chloride was performed in 520 young Swedish men doing compulsory military service. The overall frequency of nickel/cobalt positive tests was 4.2%. The prevalence of nickel/cobalt positive tests was significantly higher (p < 0.05) in 152 men with pierced earlobes (7.9%) than in those 368 with unpierced earlobes (2.7%). A history of hand eczema (7/152 = 4.6%) or other types of eczema (22/152 = 14.5%) in individuals with pierced earlobes was no more common than in those with unpierced earlobes: 24/368 = 6.5% and 51/386 = 13.9%, respectively (n.s.). Hand eczema was no more common in sensitized (1/22 = 4.5%) than in nonsensitized individuals (32/498 = 6.4%) (n.s.).

Adolescent↗
PubMed1995

Skin disease and contact sensitivity in house painters using water-based paints, glues and putties.

A dermatologic investigation of 202 construction painters included patch testing with the TRUE Test standard series and ingredients of water-based paints, glues and putties (painters' series). 32 painters had current eczema and 16 had a history of previous eczema. Of these, 16 and 9, respectively, had current and previous histories of hand eczema. Irritant reactions on the hands, characterized by dry, erythematous finely fissured skin, which healed within a few days of skin rest, were found in 18 painters. 8 painters presented dry, fissured finger tips and finger sides. The total group of painters had 25 allergic reactions to the TRUE Test standard series and 11 to the painters' series. 11 test reactions were found to be related to present or previous hand eczema: 4 cases reacted to nickel, cobalt, colophony or N-octyl-isothiazolinone; 2 each to p-tertbutylphenol-formaldehyde resin and benzisothiazolinone (BIT); and 3 to Cl + Me-isothiazolinone. 5 painters were sensitive to BIT without clinical symptoms of skin disease. Hand eczema is no more common among construction painters who work with water-based paints, glues and putties, than in an average population. There are, however, special risks of sensitization and eczema in a construction painter's work that should be considered on employment.

Adhesives↗
PubMed1995

[Biokinetics of tumor-affinity yttrium preparations--2].

After demonstrating that the application form 87Y-NTA-EDTMP-Ca is superior to the so far used citrate form of yttrium especially regarding the tumour/liver and tumour/bone ratios, the relationships between the concentrations of the components in the 87Y-NTA-EDTMP-Ca mixture and the 87Y biokinetics were investigated in tumour-bearing mice. The increase of the EDTMP and Ca2+ concentrations by several orders of magnitude caused no significant changes of tumour radioactivity but a clear radioactivity decrease in the liver, spleen and bone, respectively. The increase of the NTA concentration led also to a radioactivity decrease in all organs and tissues investigated. A significant radioactivity reduction in the tumour could be observed only after administration of rather high NTA amounts. Considerations of the tumour/background ratios depending on different compositions of the injection mixture showed the possibility of optimizing radionuclide biodistribution.

Animals↗
PubMed1995

Deficient cell cycle control in myeloid cells of patients with newly diagnosed chronic myeloid leukemia.

Cell cycle control subsequent to gamma irradiation or growth factor starvation has been studied in immative hematopoietic cells of 19 previously untreated chronic myeloid leukemia (CML) patients in chronic phase compared with 18 normal controls. CD34-positive cells were cultured for seven days in the presence of optimal concentrations of appropriate growth factors. At day 7 of culture both S-phase fraction and differentiation were identical in normal and leukemic cells. In normal cells the proportion of S-phase cells was reduced by irradiation with 500 rad from 40 +/- 3% to 16 +/- 2%. In contrast, in CML cells a reduction of S-phase cells from 35 +/- 2% to 25 +/- 3% was observed. Moreover, irradiated CML cells arrested at a smaller number of cells in G2. Similarly, a significantly higher proportion of CML cells remained in S phase after withdrawal of growth factors. Semiquantitative PCR of p21 (waf1/cip1) induction by gamma irradiation provided no evidence for a major functional deficiency of p53 response to irradiation in these cells. Our results demonstrate an abnormal cell cycle arrest in chronic-phase CML cells both after gamma irradiation and after growth factor removal. This observation might have important implications for understanding the pathogenesis of both hyperplasia of chronic phase and the development of blast crisis in CML. The molecular mechanisms underlying these abnormalities in bcr-abl-positive cells remain to be clarified.

Actins↗
PubMed1994

Purification, properties and structural aspects of a thermoacidophilic alpha-amylase from Alicyclobacillus acidocaldarius atcc 27009. Insight into acidostability of proteins.

The alpha-amylase from the thermoacidophilic eubacterium Alicyclobacillus (Bacillus) acidocaldarius strain ATCC 27009 was studied as an example of an acidophilic protein. The enzyme was purified from the culture fluid. On an SDS/polyacrylamide gel, the protein an apparent molecular mass of 160 kDa, which is approximately 15% higher than that predicted from the nucleotide sequence. The difference is due to the enzyme being a glycoprotein. Deglycosylation or synthesis of the enzyme in Escherichia coli gave a product with the mass expected for the mature protein. The amylase hydrolyzed starch at random and from the inside, and its main hydrolysis products were maltotriose and maltose. It also formed glucose from starch (by hydrolysing the intermediate product maltotetraose to glucose and maltotriose) and exhibited some pullulanase activity. the pH and temperature optima were pH3 and 75 degrees C, respectively, characterizing the enzyme as being thermoacidophilic. Alignment of the sequence of the enzyme with that of its closest neutrophilic relatives and with that of alpha-1,4 or alpha-1,6 glycosidic-bond hydrolyzing enzymes of known three-dimensional structure showed that the acidophilic alpha-amylase contains approximately 30% less charged residues than do its closest relatives, that these residues are replaced by neutral polar residues, and that hot spots for these exchanges are likely to be located at the surface of the protein. Literature data show that similar effects are observed in three other acidophilic proteins. It is proposed that these proteins have adapted to the acidic environment by reducing the density of both positive and negative charges at their surface, that this effect circumvents electrostatic repulsion of charged groups at low pH, and thereby contributes to the acidostability of these proteins.

Amino Acid Sequence↗
PubMed1994

Megestrol acetate for the prevention of hot flashes.

BACKGROUND: Vasomotor hot flashes are a common symptom in women during menopause and in men who have undergone androgen-deprivation therapy for prostate cancer. Although treatment with estrogens in women and androgens in men can attenuate these symptoms, these hormones may be contraindicated in women with breast cancer and in men with prostate cancer. Pilot trials have suggested that the progestational agent megestrol acetate can ameliorate hot flashes in both groups of patients. METHODS: The patients included 97 women with a history of breast cancer and 66 men with prostate cancer who had undergone androgen-deprivation therapy. All patients had experienced bothersome hot flashes (median number per day at base line, 6.1 for the women and 8.4 for the men). After a one-week pretreatment observation period, the patients received megestrol acetate (20 mg twice daily) for four weeks, followed by placebo for four weeks, or vice versa in a double-blind manner as determined by pretreatment randomization. The patients documented the frequency and severity of hot flashes in daily symptom diaries. RESULTS: After four weeks, hot flashes were reduced by 21 percent in the group receiving placebo first and by 85 percent in the group receiving megestrol acetate first (P < 0.001). An intention-to-treat analysis of data for all eligible treated patients showed that 74 percent of the megestrol acetate group, as compared with 20 percent of the placebo group, had a decrease of 50 percent or more in the frequency of hot flashes during the first four weeks (P < 0.001). The degree of efficacy was similar in men and women. The only side effect was withdrawal menstrual bleeding in women, generally occurring one to two weeks after the megestrol acetate had been discontinued. CONCLUSIONS: Low-dose megestrol acetate is well tolerated and can substantially decrease the frequency of hot flashes in women and men.

Breast Neoplasms↗
PubMed1994

Changes in external and internal lead load in different working areas of a starter battery production plant in the period 1982 to 1991.

Our investigation was based on routine ambient and biological monitoring data in a starter battery production plant from 1982 to 1991. This retrospective longitudinal study included 134 blue collar workers in seven main production areas (casting, lead oxide production, bunker, pasting, formation, plate stacking, assembly). Over the whole period a statistically significant decrease in blood lead concentration in the whole sample, from 48.92 micrograms/dl (1982) to 22.99 micrograms/dl (1991), could be ascertained. This positive trend could also be proven for the most important production areas. The highest internal lead load was present in employees from the formation and adjoining production areas, followed by pasting, casting and assembly. In comparison to other battery factories our results are in the lower range. Furthermore, we carried out a data linkage between air and blood lead concentrations. We were able to demonstrate a decrease in external lead load in most of the production areas, but this reduction was not so distinct as that in the blood lead concentration. These results indicate the efficiency of preventive efforts in technical work protection and especially in intensive medical supervision of the exposed workers. Influencing personal hygienic behaviour and intervention at blood lead levels of 50 micrograms/dl promises the best success in worker protection.

Air Pollutants, Occupational↗