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S Pfeifer

Publications and source records attributed to S Pfeifer.

At least 19 recordsLinked to original sources
PubMed1999

Mosaic allelic insulin-like growth factor 2 expression patterns reveal a link between Wilms' tumorigenesis and epigenetic heterogeneity.

Numerous observations link the loss of imprinting of insulin-like growth factor 2 (IGF2) and an overdosage of this growth factor gene with cancer, in general, and with Wilms' tumorigenesis, in particular. It is not known, however, if loss of imprinting correlates with specific stages of neoplasia or if allelic expression patterns vary within the tumor. By applying an allele-specific in situ hybridization technique to formalin-fixed thin sections, we show that the parental IGF2 alleles can be differentially expressed, not only in Wilms' tumors, but also in nephrogenic rests (which represent premalignant lesions) of Wilms' tumor patients. Moreover, a subpopulation of mesenchymal cells, which surrounds tumor nodules, expresses IGF2 biallelically irrespective of the imprinted state of IGF2 within the tumor. These data show that Wilms' tumorigenesis involves epigenetic heterogeneity as visualized by variable allelic IGF2 expression patterns.

Alleles↗
PubMed1999

Random monoallelic expression of the imprinted IGF2 and H19 genes in the absence of discriminative parental marks.

The IGF2 and H19 genes are genomically imprinted and expressed preferentially from the paternal and maternal alleles, respectively, during human prenatal development. The exact role of the parental imprint(s), however, is not known. To explore this issue in some detail, we have examined human androgenetic cells which by definition should be incapable of allelic discrimination given the paternal origin of both genomes. Allele-specific in situ hybridisation analysis of dispermic complete hydatidiform moles shows that IGF2 and H19 can be found to be transcriptionally active in a variegated manner, which results in the generation of random monoallelic expression patterns. This data shows that imprinted genes can be expressed monoallelically in the absence of discriminating parental marks and raises the question whether or not mechanisms underlying monoallelic expression preceded the acquisition of parental imprints during evolution.

Alleles↗
PubMed1999

The genotype and epigenotype synergize to diversify the spatial pattern of expression of the imprinted H19 gene.

Little is known of how the genetic background effects the phenomenon of genomic imprinting. The H19 gene belongs to a cluster of imprinted genes on human chromosome 11. Here we show that the alternative splicing of a human H19 transcript is genotype-specific. Moreover, this variant transcript, which lacks exon 4, is either not found at all, is widely expressed or is confined to extra-villous cytotrophoblasts in first trimester placenta, depending on a combination of the genotype and the sex of the transmitting parent.

Alleles↗
PubMed1999

Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen.

In a few patients with chronic sarcoidosis, prolonged, unacceptably high doses of corticosteroids are required to achieve symptomatic relief. In these cases, a corticosteroid-sparing drug might be administered to allow long-term treatment without the adverse effects of corticosteroids. This study examines azathioprine as a prednisolone-sparing treatment. In an open study, the course of 11 patients with chronic sarcoidosis was analysed. In an induction phase, 2 mg azathioprine x kg body weight (BW)(-1) x day(-1) in combination with 0.6-0.8 mg prednisolone x kg BW(-1) x day(-1) were administered with prednisolone being reduced to 0.1 mg x kg BW(-1) x day(-1) within 2-3 months. This was followed by a 21-22-month maintenance phase with 2 mg azathioprine x kg BW(-1) x day(-1) and 0.1 mg prednisolone x kg BW(-1) day(-1). Clinical parameters and immunological findings of bronchoalveolar lavage (BAL) were analysed. All patients had significant symptomatic relief and improvements or resolutions of physiological, serological and radiographic findings without suffering from serious adverse effects. Nine of 11 patients completed therapy after 19-26 months, and 2/11 patients terminated therapy after 8 and 12 months, respectively. Eight patients had remissions lasting 4-73 months. Three relapses occurred after 8, 18, and 22 months. During the induction phase, BAL cell composition changed and their activity in terms of cytokine release was suppressed. This preliminary study suggests that azathioprine may be effective as a corticosteroid-sparing agent in long-term therapy of sarcoidosis, but a much larger study is necessary to give the definitive answer.

Adult↗
PubMed1998

The H19 transcript is associated with polysomes and may regulate IGF2 expression in trans.

The imprinted H19 gene produces a fully processed transcript that does not exhibit any conserved open reading frame between mouse and man. Although transcriptional control elements associated with the mouse H19 locus have been shown to control the neighboring Igf2 gene in cis, the prevailing view is that the cytoplasmic H19 transcript does not display any function. In contrast to earlier reports, we show here that the H19 transcript is associated with polysomes in a variety of cell types, in both mouse and man. A possible trans-function of the H19 gene is suggested by a reciprocal correlation in trans between cytoplasmic H19 and IGF2 mRNA levels, as well as IGF2 mRNA translatability. We discuss these results in terms of their challenge to the prevailing dogma on the function of the enigmatic H19 gene, as well as with respect to the ontogeny of the Beckwith-Wiedemann syndrome, and propose that the human H19 gene is an antagonist of IGF2 expressivity in trans.

Animals↗
PubMed1997

Reduction of cytokine release of blood and bronchoalveolar mononuclear cells by ambroxol.

Ambroxol is a mucolytic agent frequently used in the treatment of chronic bronchitis. It has been reported, following clinical and in-vitro studies, that ambroxol exhibits an anti-inflammatory action. This capability was investigated by activating bronchoalveolar lavage cells and peripheral blood mononuclear cells in-vitro to elicit the release of tumor necrosis factor alpha, interleukin-2 and interferon gamma, whilst simultaneously exposing them to varying pharmacological concentrations of ambroxol (10, 1, and 0.1 microM). After 24 h it was observed that the isolated tissue-culture supernatants showed a dose-dependent reduction in the concentration of the tested cytokines; 10 microM (12 to 37% reduction) and 1 microM to (6 to 27% reduction). At 0.1 microM, a significant reduction could only be observed in the release of interleukin-2 by bronchoalveolar lavage cells. These results demonstrate, that ambroxol exhibits anti-inflammatory actions in concentrations achievable in vivo.

Ambroxol↗
PubMed1996

Spontaneous interleukin 2 release of bronchoalveolar lavage cells in sarcoidosis is a codeterminator of prognosis.

There is mounting evidence that activated interleukin 2 (IL-2)-releasing lymphocytes play a central role in the immunopathogenesis of sarcoidosis by directing inflammatory reactions and granuloma formation. In the context that a significant proportion of these cells accumulates in the lung and releases mediators, we hypothesized that different immunologically defined stages of sarcoidosis can be identified. A cohort of 89 sarcoidosis patients was allocated to four groups according to the following criteria: stage A, a low number of bronchoalveolar lavage (BAL) lymphocytes (< 20%) without IL-2 release (< 1 unit/ml in BAL cell culture supernatant); stage B, BAL lymphocytes < 20%, with IL-2 release (> or = 1 unit/ml); stage C, BAL lymphocytes > or = 20% with IL-2 release; and stage D, > or = 20% BAL lymphocytes without IL-2 release. Although patients of stages C and D (n = 49) exhibited lymphocytic inflammation, only 20/49 of these patients had activated IL-2-releasing alveolar lymphocytes. BAL of groups A and B showed a low number of lymphocytes, but the lymphocytes were activated in 20/40 patients. Forty-four patients not receiving therapy were reevaluated by pulmonary function tests 8 +/- 1 months after BAL. Progressive disease was found in 9/12 patients of group C and stable or regressing disease in 13/13 patients of group A. These results demonstrate that a combination of BAL parameters can yield prognostic information.

Adult↗
PubMed1996

[Positive role of family in coping with schizophrenic illness].

Research on the influence of family variables on the course of schizophrenia has mainly centered on the concept of expressed emotions. The emphasis of this construct is centering predominantly on potentially destructive aspects of family behaviour. The authors criticize approach as too biased towards the negative. From their clinical practice and a review of the literature, the authors argue for a more positive view of relatives' role in rehabilitation, relapse prevention and coping with schizophrenia.

Adaptation, Psychological↗
PubMed1995

Psychopathology and religious commitment--a controlled study.

The relationship between psychopathology and religious commitment was explored in a group of psychiatric patients (n = 44) with depression, anxiety disorders and personality disorders, compared with a control group of healthy subjects (n = 45). Neuroticism and the degree of religious involvement were measured in all probands. The findings did not show any correlation between neuroticism and religiosity. While life satisfaction was negatively correlated with neuroticism, there was a significantly positive correlation with religious commitment. Anxiety concerning sexuality, superego conflicts and childhood fears of God was primarily associated with neuroticism and not with religious commitment. The findings support the clinical observations that the primary factor in explaining neurotic functioning in religious patients is not their personal religious commitment but their underlying psychopathology.

Adolescent↗
PubMed1994

[Interpersonal therapy of depression--an integrative approach for clinical practice].

Interpersonal therapy of depression (IPT) has proven to be very effective in a comparative study of therapeutic modalities for the treatment of depression. It reflects contemporary research on the etiology and the nosology of depressive disorders and offers a multifactorial treatment concept. Specifically, IPT integrates aspects of biological vulnerability for depression with the psychosocial context of a person. Disturbed social relations are seen as possible causes as well as consequences of depressive disorders. IPT has the goal to reduce depressive symptomatology and to improve interpersonal functioning. It emphasizes the structured diagnosis of depression in order to help the patient to better understand his condition. Symptoms are then related to his or her interpersonal context. Therapy sessions deal with four problem areas: Grief over loss, interpersonal disputes, role transitions, and interpersonal deficits. When necessary, prescribing medication is an integral part of the therapeutic procedure. The article gives an overview of the literature and the therapeutic strategies of IPT which seems especially effective for the treatment of mild to moderate depressions in primary care.

Adult↗
PubMed1994

Belief in demons and exorcism in psychiatric patients in Switzerland.

Belief in demons as the cause of mental health problems is a well-known phenomenon in many cultures of the world. However, there is little literature on this phenomenon in Protestant subcultures of the West. The author conducted a systematic investigation of the prevalence of this attribution in 343 mainly Protestant out-patients of a psychiatric clinic in Switzerland, who described themselves as religious. Of these, 129 (37.6 per cent) believed in the possible causation of their problems through the influence of evil spirits, labelling this as 'occult bondage' or 'possession'. One hundred and four patients (30.3 per cent) sought help through ritual 'prayers for deliverance' and exorcism. Prevalence of such practices was significantly related to diagnosis (p < .01) and to church affiliation (p < .005). Patients in charismatic free churches suffering from anxiety disorders and schizophrenia reported the highest rate of exorcistic rituals (70 per cent), and patients with adjustment disorders from traditional state churches the lowest (14 per cent). The various forms and functions of these healing rituals are described. Although many patients subjectively experienced the rituals as positive, outcome in psychiatric symptomatology was not improved. Negative outcome, such as psychotic decompensation, is associated with the exclusion of medical treatment and coercive forms of exorcism.

Adult↗
PubMed1994

Beryllium-induced disturbances of the murine immune system reflect some phenomena observed in sarcoidosis.

Sarcoidosis is a systemic granulomatous disorder of unknown origin. In respect to clinical and immunological characteristics, it is indistinguishable from berylliosis. As an approach to develop a murine model reflecting some aspects of sarcoidosis, we attempted to induce berylliosis in mice by treating inbred F1 mice (C57B16 x DBA/2) with 3 mg beryllium sulfate (BeSO4) per kg body weight intraperitoneally. Either pure BeSO4 or BeSO4 in combination with incomplete Freund's adjuvant was administered. Alternatively, pure BeSO4 was injected 2 days after a single application of cyclophosphamide (150 mg/kg). The spleen index, the spontaneous and phorbolmyristate acetate (PMA)-induced radical oxygen intermediates (ROI) released by peritoneal macrophages, and the proliferative activity of spleen mononuclear cells in response to BeSO4 and concanavalin A (ConA) were evaluated and compared to the corresponding changes observed in sarcoidosis. In all three modes of BeSO4 treatment, the spontaneous ROI release by peritoneal macrophages was significantly elevated. These elevations were very similar to those observed with alveolar macrophages in active sarcoid alveolitis. After BeSO4 treatment, a small proliferative activity of spleen mononuclear cells in response to BeSO4 could be observed. Further, BeSO4-treated spleen mononuclear cells exhibited a markedly reduced response to ConA stimulation (approximately 20% of control) which parallels the reduced proliferative capacity of sarcoid peripheral blood mononuclear cells (approximately 45% of control). This reduction could be abolished by pretreating the mice with cyclophosphamide. BeSO4 treatment in combination with incomplete Freund's adjuvant resulted in a significant increase of spleen mononuclear cell proliferation (1.9-fold) after in vitro stimulation with BeSO4, and prevented the low responsiveness to ConA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[Multiple personality disorder. Presentation of 2 cases and a model of the etiology].

Although the syndrome of Multiple Personality Disorder (MPD) has received much interest in the international literature, there have been virtually no professional articles on the topic in German over the last 70 years. This is a report on two cases with nine and 70 persons respectively. Both had undergone severe and prolonged sexual abuse in childhood. Compared with DSM-III-R, the ICD-10 criteria seem to reflect historic reports on alternating personalities rather than recent empirical research on multiple personality. The proposed etiological model postulates that extreme trauma in childhood can result in dissociative vulnerability persisting into adulthood.

Adolescent↗