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Biomedical subjects

J Berger

Publications and source records attributed to J Berger.

At least 19 recordsLinked to original sources
PubMed1992

Activation of an inducible c-FosER fusion protein causes loss of epithelial polarity and triggers epithelial-fibroblastoid cell conversion.

As a novel approach to studying the modulation of the polarized epithelial phenotype, we have expressed c-Fos and c-Myc estrogen receptor fusion proteins (c-FosER and c-MycER) in mammary epithelial cells. The hybrid proteins could be activated by estrogen for defined time periods and after the cells had achieved their fully polarized organization. Activation of c-MycER deregulated proliferation but did not affect epithelial polarity. Short-term activation of c-FosER induced the reversible loss of morphological and functional cell polarity. In contrast, long-term stimulation of c-FosER caused the cells to depolarize irreversibly, to invade collagen gels, and to undergo epithelial-fibroblastoid cell conversion. Our data suggest that Fos proteins are important in modulating the epithelial phenotype both in normal tissue development and in invasive processes.

Animals↗
PubMed1992

Cancer of the stomach and the colon-rectum among workers in a coke gas plant.

Four thousand nine hundred and eight male workers of the Hamburg gas plant, employed for 10 or more years during the period from January 1, 1900 to December 31, 1989, have been traced for cancer mortality. Based on their jobs, they were grouped into three subcohorts: gas furnace workers, workers in other parts of the plant, and white-collar workers. Despite the general "healthy worker effect," gas furnace workers showed a significant incidence of cancer of all sites (standardized mortality ratio [SMR] = 186), particularly cancers of the lung (SMR = 288), stomach (SMR = 177), and the colon-rectum (SMR = 184). In comparison to the death rates of white-collar workers, the manual workers in other parts of the plant also showed an excess of cancer mortality for cancer of these sites. The reason for this excess in cancer mortality seems to be due to the working conditions. The results contribute to the current evidence that exposure to coal carbonization fumes causes not only lung cancer, but also cancers of the stomach and colon-rectum.

Adult↗
PubMed1992

Transoesophageal echocardiography during removal of a caval filter in a patient at high risk of massive pulmonary thromboembolism.

A new type of vena caval filter was to be removed from a woman who had a high risk of massive pulmonary thromboembolism because of extensive thrombus in the iliac vein incorporating the filter. The removal was performed under general anaesthesia in the cardiac operating theatre using transoesophageal echocardiography to monitor the right heart and the pulmonary artery during the critical phase of removal. The manoeuvre succeeded with only insignificant embolisation occurring, and that was identified by transoesophageal echocardiography.

Echocardiography↗
PubMed1992

Dominant-negative mutants are clustered in a domain of the human T-cell leukemia virus type I Rex protein: implications for trans dominance.

The 27-kDa Rex trans-acting protein appears to be essential for replication of human T-cell leukemia virus type I. Mutations introduced outside of the Rex RNA-binding domain-nucleolar localization signal display either wild-type activity or, conversely, yield dominant-negative proteins. We generated missense mutations in a particular domain of the Rex protein (amino acid residues 54 to 69) which is characterized by a cluster of dominant-negative mutants. Our results indicate that amino acids 57 to 67 are critically important for Rex function mediated through the RxRE cis-acting RNA sequence. Within this domain, only amino acids 61 to 63 could be mutated without loss of function. All other missense and deletion mutants yielded dominant-negative proteins. In vitro RNA-binding studies performed with glutathione S-transferase-Rex fusion proteins demonstrated that all of the mutant Rex proteins interacted specifically with RxRE RNA. Analysis of chimeric Rex-Rev proteins suggests that this Rex domain is important for oligomerization.

Amino Acid Sequence↗
PubMed1992

Controlling Stroop effects by manipulating expectations for color words.

An important characteristic of automatic processing is its uncontrollability. The Stroop phenomenon is regarded as a prototypical example of this characteristic of automatic processing, hence, the Stroop effect should not change when the percentages of color words versus neutral stimuli are manipulated to induce controlled processing. We found that Stroop interference decreased as the percentage of color words increased. Furthermore, the magnitude of the inhibitory component of the Stroop effect was negatively correlated with the percentage of color words; the facilitatory component was insensitive to the manipulation. These results suggest that the Stroop effect is controllable (see Logan, 1980) and that the locus of control is postlexical. The results also suggest that facilitation and inhibition are produced by different mechanisms and challenge those models of the Stroop phenomenon (e.g., Cohen, Dunbar, & McClelland, 1990; Phaf, Van der Heijden, & Hudson, 1990) that assume that a single processing mechanism causes facilitation and inhibition and that control affects facilitation and inhibition alike (Logan, 1980).

Adult↗
PubMed1992

[Treatment of ischemic cerebrovascular accidents with hyperbaric oxygenation].

The authors present eleven year's experience with comprehensive treatment of patients who suffered an ischemic cerebrovascular attack. This comprises so-called conventional treatment of cerebrovascular attacks and also hyperbaroxia, i.e. administration of oxygen under high partial pressure. The authors used a therapeutic pressure of 0.2 MPa for 90 minutes in individual exposures. Of 31 treated patients 23 improved, i.e. 76%; eight improved slightly, eight significantly and seven substantially. The condition of the remainder did not change. Hyperbaroxia should therefore be used everywhere where this method is available.

Adult↗
PubMed1992

ROENTGEN: case-based reasoning and radiation therapy planning.

ROENTGEN is a design assistant for radiation therapy planning which uses case-based reasoning, an artificial intelligence technique. It learns both from specific problem-solving experiences and from direct instruction from the user. The first sort of learning is the normal case-based method of storing problem solutions so that they can be reused. The second sort is necessary because ROENTGEN does not, initially, have an internal model of the physics of its problem domain. This dependence on explicit user instruction brings to the forefront representational questions regarding indexing, failure definition, failure explanation and repair. This paper presents the techniques used by ROENTGEN in its knowledge acquisition and design activities.

Artificial Intelligence↗
PubMed1992

[Prognostication of chronic Ph+ myeloid leukemia using the PHCML.EXE computer program].

In 193 patients with Ph-positive chronic myeloid leukaemia (CML) Sokal's calculation formulae prognosticating initial risk status were applied, using the computer program PHCML. The aim of this study was to the prognostic reproducibility of these prognostic staging systems in our patient population. Our results confirm the previous conclusions that prognostic discrimination is possible at the time of diagnosis of CML but in our patients with poorer prognosis the stratification seems to be more accurate. No significant advantage was achieved when we prognosticated our patients younger than 46 years using the formula recommended by Sokal et al. specifically for younger patients. We analyzed different criteria when segregating patients in groups with better or poorer prognosis. We found that the coefficient of the patient's relative risk as the boundary, was 1.9 our patient's group contrary to 1.2 in Sokal's studies.

Adolescent↗
PubMed1992

[Quality control in hematology].

Qualified quality control is a necessary part of modern haematology: we cannot deem laboratory results reliable until effective quality checking is included. Quality assessment includes external (national, regional) and internal (intra-laboratory) control. We suggest to found a Czech national external quality control agency for haematology based on principles which were declared by the World Health Organization. Internal control includes correct identification of samples, analytical control (standardization of test, evaluation of accuracy and precision) and biological quality control (history of patient's characteristics, relation to other laboratory results in clinical context). The deviation index, which is expressed either as a number or verbally 'excellent', 'good', 'satisfactory', or 'unsatisfactory', can supply rapid information on the quality of results in the haematological laboratory.

Hematology↗
PubMed1991

Cancer mortality among workers in chemical plant contaminated with dioxin.

Dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin or TCDD) can arise as a contaminant in the production of herbicides. It causes chloracne in those exposed to it but its human carcinogenicity has been a matter of dispute. We report here a mortality follow-up of 1583 workers (1184 men, 399 women) employed in a chemical plant in Germany that produced herbicides, including processes contaminated with TCDD. Production of TCDD was reduced from 1954 after an outbreak of chloracne. Vital status up to 1989 was determined for 97.1% of workers hired between 1952 and 1984, and 367 deaths (313 men, 54 women) were recorded. A malignant neoplasm was the underlying cause of death in 93 men and 20 women. Standardised mortality ratios (SMR) were calculated with, as references, national mortality statistics for West Germany and deaths in a cohort of male gas workers; for total cancer mortality they were 1.24 (95% confidence interval 1.00-1.52) and 1.39 (1.10-1.75), respectively, among men. Cancer mortality was increased among men with 20 or more years of employment (SMR = 1.87 [Germany] and 1.82 [gas workers]) and among men who began employment before 1955 (SMR = 1.61 and 1.87). The group with suspected highest exposure to TCDD had SMRs of 1.42 and 1.78. Only 7% of cohort women worked in the high exposure locations in the plant, compared with 39.6% of men, and no increased risk of cancer mortality was observed among women; but breast cancer mortality was raised (SRM = 2.15). These results, together with a US occupational study and a German investigation of accidental exposure, support the hypothesis that TCDD is a human carcinogen.

Cause of Death↗
PubMed1991

Positive phase II study in the treatment of advanced malignant melanoma with fotemustine.

To date, dacarbazine (DTIC) has been the most effective drug in the treatment of advanced metastatic melanoma, achieving response rates of up to 28% (mean, 21%). Multidrug responses were generally no better than those obtained using monotherapy. A quite promising clinical trial was conducted using the new nitrosourea fotemustine. A total of 19 patients presenting with advanced malignant melanoma (clinical stage IV according to the 1987 UICC classification system) underwent treatment involving a more rapid infusion of the drug and a reduction in the rest period from 5 to 3 weeks. This monotherapy with fotemustine yielded two complete responses and seven partial responses; in addition, four patients showed no change and six cases progressed after the induction cycle (median duration of response to date, 7.6 months, including four cases that have not relapsed). Fotemustine was well tolerated by the patients, with the only mild side effects being thrombocytopenia, leukocytopenia and easily controlled nausea/vomiting. Preclinical studies performed previously indicated that fotemustine inhibits enzymes involved in the ribonucleotide reduction pathway (i.e. DNA synthesis), whereby responding patients (n = 3) appeared to favor the thioredoxin reductase/thioredoxin electron transfer to ribonucleotide reductase, whereas non-responders (n = 4) expressed the alternate glutathione reductase/glutaredoxin mechanism. The 47% response rate obtained in these studies vs the 24% reported previously for fotemustine may reflect variations in enzymes in the ribonucleotide reduction pathway in different patients. However, the efficacy of fotemustine against advanced melanoma warrants more extensive trials of this drug, especially since the quality of life of the patients during and after chemotherapy was not severely affected.

Adult↗
PubMed1991

Structure-affinity relationships of 12-sulfonyl derivatives of 5,8,8a,9,10,11,12,12a,13,13a-decahydro-6H-isoquino[2,1-g][1 ,6] naphthyridines at alpha-adrenoceptors.

Analogues of the potent alpha 2-adrenoceptor antagonist (8aR,12aS,13aS)-5,8,8a,9,10,11,12,12a,13,13a- decahydro-3-methoxy-12-(methylsulfonyl)- 6H-isoquino[2,1-g][1,6]naphthyridine (1b) were prepared and evaluated for alpha 1- and alpha 2-adrenoceptor affinity. Affinity for alpha 2-adrenoceptors was assessed by displacement of [3H]yohimbine from rat cerebral cortical membranes and although 1b and close structural analogues demonstrated high affinity, none were selective for the alpha 2A or alpha 2B subtypes reputedly present in this tissue. All of the high affinity alpha 2-adrenoceptor ligands were, however, selective with respect to [3H]prazosin (alpha 1) binding. Affinity for [3H]yohimbine-labeled alpha 2-adrenoceptors was found to be highly dependent on the stereochemistry of the tetracyclic system. The 8a beta,12a alpha,13a alpha diastereomer of 1 (56) had moderate affinity for alpha 2-adrenoceptors while the 8a beta,12a beta,13a alpha diastereomer (55) had very low affinity. The affinity and selectivity of these agents for alpha 2-adrenoceptors was found to correspond to that observed for several isomeric yohimbine analogues which have similar relative and absolute stereochemistries. Deviation from the structure of 1 by opening the B ring, changing the position of the sulfonamide nitrogen, or changing the attachment of the D ring led to a dramatic decrease in alpha 2-adrenoceptor affinity. High binding affinity was found to correlate with functional antagonism in the guinea pig ileum. The reversal of clonidine-induced mydriasis in the rat was used to assess bioavailability and indicated that 1b was a potent alpha 2-adrenoceptor antagonist in vivo.

Adrenergic alpha-Antagonists↗
PubMed1991

Low catalase levels in the epidermis of patients with vitiligo.

Suction blister roofs taken from the involved and uninvolved epidermis of patients with vitiligo showed a consistent reduction in levels of catalase compared to normal healthy controls of matched photo-skin types (Fitzpatrick classification). A decrease in catalase activity is expected to increase the concentration of hydrogen peroxide in the epidermis of these patients. Hydrogen peroxide functions as a reversible inhibitor of human tyrosinase with a KI of 8 X 10(-6) M. Also, hydrogen peroxide undergoes photochemical reduction yielding highly reactive hydroxyl radicals (OH.) and hydroxyl ions (OH-) mainly by the Haber-Weiss reaction. Hydroxyl radicals are capable of bleaching constitutional melanin and cause membrane lysis through lipid peroxidation reactions. Hydroxyl ions increase the pH in the epidermis, and as a consequence glutathione reductase activity is increased in patients with vitiligo compared to controls. Based on these new results, together with the previously reported calcium transport defect, a new hypothesis has been formulated for the pathogenesis of vitiligo.

Catalase↗
PubMed1991

[Immediate breast reconstruction with tissue expander].

The technique of immediate breast reconstruction, using the tissue expander and replacing it with a permanent silicone prosthesis, has been applied with increasing frequency during the past several years. We chose this technique for immediate breast reconstruction because of its simplicity, rapidity when combined with mastectomy, and good esthetic results. We have performed 29 immediate breast reconstructions in the past 1.5 years in patients ranging from 22 to 72 years (mean 47). The insertion of the tissue expander added only 20-30 minutes of operating time for the mastectomy, and did not prolong hospitalization. Before we began to replace the expander with a permanent silicone prosthesis there were complications in 4 patients (14%). These included development of a seroma in 3, 1 of which became infected 40 days after insertion of the tissue expander, and capsular contraction in a patient who had previously had radiotherapy to her breast. The case with the infection was the only failure and the expander had to be removed. Immediate reconstruction of the breast is easily performed and can be of tremendous psychological benefit to mastectomy patients. Chemotherapy or radiotherapy are not contraindications to this type of reconstruction.

Adult↗
PubMed1990

Bone marrow and spleen morphology following haemolytic anaemia in adult laboratory rats of various age groups.

We induced toxic-haemolytic events in 8, 11 and 29-w-old rats after single dose of nitrobenzene, 3-chloro-4-benzyloxyphenacetic acid and phenacetin administered orally. Large individual variability of haematological changes in rat marrow and spleen morphology was found. The use of groups of laboratory rats of different age significantly modified reactions in characteristics investigated but common simple age-related changes were not clearly demonstrated.

Age Factors↗
PubMed1990

Computer evaluation of reference limits.

Reference limits are necessary for medical laboratory to provide objective information on health in concrete characteristics. With respect to changeability of some factors influencing upon homeostasis, reference limits must be determined and redetermined in each clinical laboratory with the high degree of the internal quality control system. The presented program computing reference limits and providing expert consultations facilitates solution.

Adult↗
PubMed1979

Analysis of clinical laboratory data by biplot methods using a three-dimensional display: discrimination of renal stone-patients with idiopathic hypercalciuria and primary hyperparathyroidism.

The biplot technique is a very useful graphical method to display the relationships between row and column characteristics in two-way tables. This method is applicable as long as the rank-2 approximation explains a large part (e.g. 95%) of the whole variability. However, since in large tables only a rank-3 approximation will yield such a high degree of explanation, a three-dimensional biplot technique has been introduced, using a 3d-screen as a matter of presentation of clinical laboratory data. The value of such a procedure is illustrated using as a clinical example a patient population with recurrent renal stone formation due either to primary hyperparathyroidism or to idiopathic hypercalciuria.

Adult↗