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Biomedical subjects

A Möller

Publications and source records attributed to A Möller.

At least 37 records · Page 2Linked to original sources

Protein kinase C theta cooperates with Vav1 to induce JNK activity in T-cells.

Here we show that in human T-cell leukemia cells Vav1 and protein kinase C theta (PKCtheta) synergize for the activation of c-Jun N-terminal kinase (JNK) but not p38 MAP kinase. Vav1 and PKCtheta also cooperated to induce transcription of reporter genes controlled either by AP-1 binding sites or the CD28RE/AP composite element contained in the IL-2 promoter by stimulating the binding of transcription factors to these two elements. Dominant negative versions of Vav1 and PKCtheta inhibited CD3/CD28-induced activation of JNK, revealing their relative importance for this activation pathway. Gel filtration experiments revealed the existence of constitutively associated Vav1/PKCtheta heterodimers in extracts from unstimulated T-cells, whereas T-cell costimulation induced the recruitment of Vav1 into high molecular weight complexes. Several experimental approaches showed that Vav1 is located upstream from PKCtheta in the control of the pathway leading to synergistic JNK activation. Vav1-derived signals lead to the activation of JNK by at least two different pathways. The major contribution of Vav1 for the activation of JNK relies on the PKCtheta-mediated Ca(2+)-independent synergistic activation pathway, whereas JNK is also activated by a separate Ca(2+)-dependent signaling route.

Base Sequence↗

Two-dimensional gel electrophoresis: a powerful method to elucidate cellular responses to toxic compounds.

Humans are exposed to a variety of environmental toxicants and combinations thereof, and a large number of interacting factors contribute to an individual's risk for disease. Therefore, new strategies in toxicological research are needed for efficient screening of environmental hazards on complex living systems. The rapidly expanding field of proteomics relies heavily upon the use of two-dimensional gel electrophoresis (2-DE) of protein samples. 2-DE is a key separation technique in proteome analysis due to its advantage of simultaneous separation of thousands of proteins at a time, excellent reproducibility, and ability to exhibit post-translational modifications. Therefore, 2-D proteome analysis is becoming a popular method of choice to detect differentially expressed proteins between proteome profiles after exposure to toxicants. The goal of this study was to examine the response of pancreas carcinoma cells to increasing concentrations of the cytotoxic agent daunorubicin (DRC). The proteomic investigation revealed a number of proteins that were up-regulated by DRC treatment, some in a dose-dependent manner. However, these changes were not seen by reverse transcriptase-polymerase chain reaction. The determination of proteome changes following exposure to xenobiotics will aid our understanding of the mechanisms of their toxicity as well as providing the possibility for the establishment of biomarkers that can be used in risk assessment as well as for the identification of individual susceptibility factors.

Adenocarcinoma↗

Thermal decomposition of (NH4)2[PdCl6] studied by in situ X-ray absorption spectroscopy.

In situ X-ray absorption near edge structure (XANES) investigations were carried out at chlorine K edge and palladium L3 edge to study the mechanism of the thermal decomposition of ammonium hexachloropalladate. The spectra show a characteristic feature for the initial step that might be explained as the formation of the precursor via ligand exchange (Cl --> NH3). Multiple scattering calculations (Feff 8) for the Cl K, Pd and Rh L3 edges were successful in simulating the XANES spectra of the precursor as well as the reference compounds (NH4)2 [PdCl4] and (NH4)3[RhCl6].

Journal Article↗

Off-site evaluation of liver lesion detection by Gd-BOPTA-enhanced MR imaging.

The aim of this study was to determine the efficacy of Gd-BOPTA-enhanced MRI in liver lesion detection in comparison with unenhanced MRI and dynamic CT. The image sets of 148 of 151 patients enrolled in a multicenter German phase-III trial were evaluated by two independent radiologists unaffiliated with the investigating centers. Patients underwent a routine MRI protocol comprising T2- and T1-weighted spin-echo and T1-weighted gradient-echo (GE) sequences pre and 1 h post 0.1 mmol/kg Gd-BOPTA (Bracco-Byk Gulden, Konstanz, Germany). Additionally, a serial T1-weighted GE scan was performed after administration of the first half of the dose. All patients underwent dynamic contrast-enhanced CT. The evaluation was performed with regard to the number and size of lesions detected per patient by each modality or sequence. Furthermore, all pre CM and pre + post CM image sets were analyzed for number of lesions per patient. Both readers detected significantly more lesions in the contrast-enhanced image set compared with the unenhanced image set (32 and 39 %, respectively; p < 0.0001). While contrast-enhanced CT detected a similar number of lesions to unenhanced MRI, it was clearly inferior to contrast-enhanced MRI (reader 1: p = 0.0117; reader 2: p = 0.0225). Of the T1-weighted scans performed, the dynamic and late T1-weighted GE exams contributed most to the increased lesion detection rate (reader 1: p = 0.0007; reader 2: p = 0.0037). The size of the smallest lesion detected by means of MRI was significantly larger in the pre-CM image sets than in the pre + post CM image sets (reader 1: p = 0.001; reader 2: p < 0.0001). Gd-BOPTA-enhanced MRI detected significantly smaller lesions than contrast-enhanced CT (reader 1: p = 0.0117; reader 2: p = 0.0925). Gd-BOPTA-enhanced MR imaging improves liver lesion detection significantly over unenhanced MRI and dynamic CT.

Adult↗

[Psychopathy in forensic psychiatry].

The review refers to the construct of psychopathy which is of increasing relevance for forensic psychiatry and psychology, especially empiric studies on legal prognosis and predictors of therapeutic efficacy. Psychopathy is related to early-onset delinquency, number and severeness of violent crimes, number of sexual victims in rapists, and unfavorable legal prognosis. Recent research has also indicated that the treatment of psychopaths is complicated by low levels of motivation and high rates of attrition. In psychiatric-diagnostic terms, psychopathy is related to substance abuse and dependency and to cluster A and B personality disorders (PD), especially to antisocial and borderline PD. In juvenile with "psychopathic tendencies", a relationship to impulsivity, emotional and behavioral difficulties, and learning behavior (card sorting test) had been shown and interpreted by reference to an anatomical level. In connection with these findings, the relevance of psychopathic disorder for testimonies on legal responsibility should also be discussed again. Further research on psychopathy, especially psychiatric morbidity and psychosocial functioning in non-forensic groups, is needed.

Animals↗

Spouses of first-ever stroke patients: psychological well-being in the first phase after stroke.

BACKGROUND AND PURPOSE: A stroke affects not only the patient but also the spouse. To better support the spouse during the acute phase of stroke, knowledge is needed about his or her experience with the situation. The aim of the present study was to study the well-being of the spouses of stroke patients during the acute state of stroke and to identify factors that may influence their well-being. METHODS: Eighty-three consecutively enrolled spouses of first-ever stroke patients <75 years old participated. Their psychological well-being, measured by the Psychological General Well-Being Index 10 days after the stroke, was compared with norm values. Multiple analyses of correlation were performed to investigate the effects on psychological well-being of (1) age and sex, (2) level of impairment of the stroke patient, and (3) intrapersonal variables such as previous life satisfaction and view of the future. RESULTS: The study group showed significantly lower psychological well-being compared with norm values except for the dimension of general health. The variables that correlated significantly with the Psychological General Well-Being total score were the sensorimotor impairment of the stroke patient and the "view of the future." This view of the future also correlated significantly with the level of functional ability of the stroke patients. CONCLUSIONS: During the acute phase of stroke, the severity of the stroke has an impact on the spouse's image of his or her future life, whereas the individual appraisal of personal consequences and of his or her own coping capacity seems to have a greater impact on the psychological well-being of the spouses than does the objective state of disability.

Acute Disease↗

Human micro-calpain: simple isolation from erythrocytes and characterization of autolysis fragments.

Heterodimeric p-calpain, consisting of the large (80 kDa) and the small (30 kDa) subunit, was isolated and purified from human erythrocytes by a highly reproducible four-step purification procedure. Obtained material is more than 95% pure and has a specific activity of 6-7 mU/mg. Presence of contaminating proteins could not be detected by HPLC and sequence analysis. During storage at -80 degrees C the enzyme remains fully activatable by Ca2+, although the small subunit is partially processed to a 22 kDa fragment. This novel autolysis product of the small subunit starts with the sequence 60RILG and is further processed to the known 18 kDa fragment. Active forms and typical transient and stable autolysis products of the large subunit were identified by protein sequencing. In casein-zymograms only the activatable forms 80 kDa+30 kDa, 80 kDa+22 kDa and 80 kDa+18 kDa displayed caseinolysis.

Autolysis↗

Women with Turner syndrome: psychological well-being, self-rated health and social life.

Psychological well-being, self-rated health and social situation were investigated in a cross-sectional multidisciplinary study of 63 women with Turner syndrome (TS; mean age 31.5 years, range 18-59 years). The psychological examination included a semi-structured interview, and use of two standardized self-rating scales, the Psychological General Well-being Index (PGWB) and the Nottingham Health Profile (NHP). Psychological well-being and self-rated health were similar in the women with TS and Swedish female normative data, matched for age. However, the women with TS reported more social isolation than the normative group. Within the TS group, the oldest women reported more psychological distress and poorer health than the youngest. Those with impaired self-rated health reported more emotional distress. The women with TS were studying or in employment to the same degree as the general population, although fewer were cohabiting. In the interview, both negative and positive consequences of TS were reported. This study did not find any evidence for impaired psychological well-being, although it did indicate that women with TS experience more difficulties in the area of social and partner relationships.

Adolescent↗

Synthesis and biological evaluation of novel piperidine carboxamide derived calpain inhibitors.

Calpain inhibitors which are derived from piperidine carboxamides in the P2 region were prepared and evaluated for mu-calpain inhibition. In particular, the keto amides 11f and 11j have Ki of 30 and 9 nM and display a more than 100-fold selectivity over the closely related cysteine protease cathepsin B. Furthermore, these compounds inhibit NMDA induced convulsions in mice indicating that calpain inhibition in brain results in some anticonvulsive properties.

Animals↗

[Disturbed sleep caused by sleep apnea. To the sleep laboratory for diagnosis?].

Since it was shown that numerous neurological, psychiatric and internal illnesses have characteristics manifested during, or influenced by sleep, somnology has been playing a clinically more and more important role. Among the 88 diagnoses listed by ICD, not only insomnia, but also sleep-related respiratory disorders, in particular the obstructive sleep apnea syndrome, are of special importance. Sleep apnea is associated with coronary heart disease, myocardial insufficiency and other pathological conditions. Already in the doctor's office, a carefully taken history (nocturnal apnea alternating with irregular snoring, and diurnal sleepiness) can arouse an appropriate suspicion. This can be confirmed by an ambulatory polygraphic exploration. The definitive diagnosis is then established with the aid of polysomnography in the sleep lab where specific treatment is also initiated.

Diagnosis, Differential↗

[Fundamentals of scientifically based ethics in the works of Eugen Bleuler].

The name Eugen Bleuler is almost exclusively linked with matters concerning the nosology of schizophrenia, general psychopathology, and the relationship of clinical psychiatry with psychoanalysis. His bibliography lists various works dealing with contemporary themes about legislation, the fight against alcoholism, and, for the most part from later years, with themes about general psychology. In this article, material from Bleuler's texts are reviewed, including some which have been inaccessible up to now, which either allow interpretative conclusions on ethical grounds or have this explicitly as a topic. In particular, the analysis focuses on Bleuler's work "The Scientific Fundamentals of Ethics", published in 1939. Written in a time widely viewed as disorientated, the author coherently and systemically comments on the issue of a 'new' ethic. The anti-religious and anti-philosophical positions already demonstrable in some of his earlier works will be shown. According to his conception of a scientifically based ethic, the idea of social suitability is of utmost importance and also recognisable in the animal world as a general principle of nature. Bleuler perceives the ethical 'instinct' as inherent; its absence characterises the image of an 'moral idiot', which was already a theme in his earlier works. His statements about matters concerning euthanasia are presented and, furthermore, it will be attempted to construct from his texts an underlying global view. Concerning these ethical issues, it also can be shown once more that the elderly Bleuler was hardly influenced by psychoanalytical perspectives.

Ethics, Medical↗

Inhibition of cytokine secretion from human leukemic mast cells and basophils by H1- and H2-receptor antagonists.

H1-type antihistamines have recently been reported to inhibit cytokine secretion from human and murine mast cells and basophils. In order to confirm and expand these studies, we have compared several H1-blockers and the H2-blocker ranitidine for their effect on TNF-alpha, IL-3, 6, 8 and GM-CSF release from human leukemic mast (HMC-1) and basophilic (KU812) cells, compared to dexamethasone. Cells were stimulated for 24 h with phorbol myristate acetate (25 ng/ml) and calcium ionophore A 23187 (2.5x10(-7) M) alone or with the drugs added at 10(-4) to 10(-15) M, and production of cytokines was measured by ELISA. All antihistamines caused a dose-dependent inhibition of TNF-alpha release from HMC-1 cells, with maximal effects at 10(-12) M for azelastine, 10(-9) M for loratadine and cetirizine, and 10(-8) M for ranitidine. The inhibitory potency of H1-blockers on cytokines from HMC-1 cells was TNF-alpha >IL-8> or =IL-6> or =IL-3, with no significant effects on GM-CSF. In KU812 cells which failed to secrete TNF-alpha and GM-CSF, the sequence was IL-6 >IL-8 after preincubation. Dexamethasone inhibited all cytokines, but ranitidine only TNF-alpha and IL-3. Antihistamines had no effect on calcium flux in resting or stimulated cells. At the mRNA level, inhibition was only seen with KU812 cells and IL-8 in the presence of azelastine at 10-(10) M. These data show thus distinct inhibitory patterns for different antihistamines during cytokine production from human mast cells and basophils which may contribute to the anti-inflammatory effects of these drugs during treatment of allergic diseases.

Basophils↗

Erythema elevatum diutinum--evidence for disease-dependent leucocyte alterations and response to dapsone.

Erythema elevatum diutinum (EED) is a type of leucocytoclastic vasculitis of unknown aetiology. We report a patient with unusually widespread and disabling EED that had been unresponsive to corticosteroids and antibiotics, but resolved on dapsone. Biopsies of fresh lesions showed typical features of leucocytoclastic vasculitis, with prominent neutrophil infiltration, marked expression of the beta(2)-integrins CR3 and LFA-1, and increased mast cell numbers. Older lesions exhibited granulation tissue and fibrosis, macrophages were more dominant, beta(2)-integrins were expressed less markedly, and mast cell numbers were lower. In vitro chemotaxis of the patient's peripheral blood neutrophils prior to treatment showed increased random migration and directed migration towards interleukin-8 (by 424%), but a profoundly decreased responsiveness towards the bacterial peptide analogue N-formyl-methionyl-leucyl-phenylalanine (fMLP) (by 98%). These values returned to normal after dapsone treatment and clinical improvement 5 months later. These findings support the concept that in EED, activation via cytokines such as interleukin-8 allows a selective recruitment of leucocytes to tissue sites, while immune complexes and bacterial peptides sustain the persistent local inflammatory infiltrate and the leucocytoclastic vasculitis.

Anti-Inflammatory Agents, Non-Steroidal↗

Experiencing liver transplantation: a phenomenological approach.

In order to promote health, nurses and other health care professionals need to discover and articulate the meaning that is implicit in experiencing life after liver transplantation. From such an understanding, appropriate nursing interventions can be based. The aim of this study was to investigate the subjective experiences of the meaning of having a liver transplant, 1 year after the transplantation. After approval from the ethics committee at Goteborg University, 12 patients, nine women and three men, were interviewed. The study sample was chosen strategically to represent common diagnoses preceding liver transplantation. A phenomenological approach was chosen for the study. Analyses of the interviews were based on a modified version of a phenomenological method by Karlsson. Seven categories emerged: facing the inevitable; recapturing the body; emotional chaos; leaving the experts; family and friends; the threat of graft rejection; and honouring the donor. Having undergone a liver transplant meant living in a paradoxical situation. Knowing that you survived, it was a struggle to regain physical strength under great emotional stress. The recipients had to self-administer life-long medication, recognize symptoms indicating a potential problem and monitor for the possibility of graft rejection. Social support was essential for recovery. Meeting others with the same experience helped liver-transplanted patients to deal with their identity crises as well as undergo a transformation from being utterly unique to a survivor among others. The clinical implications from this study are that interventions, such as patient education, and social and mental support, are important tools to optimize both self-care capacity and the ability to maintain a healthy perception of identity after having a liver transplant at least up to 12 months post-transplant.

Activities of Daily Living↗

Family function in families with children of normal height and in families with short children.

UNLABELLED: The purpose of this study was to examine any differences regarding cohesion and adaptability between Swedish families with children of normal stature (group A) and those with children of short stature (group B). Cohesion and adaptability were measured using a Swedish translation of the third version of the self-report questionnaire FACES (Family Adaptability and Cohesion, Evaluation Scales). Most of the 55 families in group A and most of the 49 families in group B appeared to be well balanced with regard to cohesion and adaptability. There was no statistically significant difference between the two groups concerning the variable cohesion. Significant differences were found in adaptability: fathers in group A had higher values than mothers in group A and than mothers and fathers in group B. CONCLUSION: There are no major differences between families with children of normal stature and those with short children. However, it was found that fathers with children of normal stature perceived a greater adaptation within their families compared with mothers with children of normal stature and mothers and fathers with children of short stature.

Body Height↗

Bronchogenic cyst. A rare differential diagnosis of retroperitoneal tumors.

Subdiaphragmatic bronchogenic cysts are rare, and those located retroperitoneally are exceptional. A review of the English-language literature revealed only 16 reported cases. We describe an additional case of a retroperitoneal cyst presenting as an asymptomatic adrenal mass and discuss clinical, radiographic, surgical and pathological findings as well as its embryological background.

Bronchogenic Cyst↗

Subchronic toluene exposure in low concentrations produces signs of reduced dysfunction in the 6-hydroxydopamine lesioned nigrostriatal dopaminergic system of the rat.

The effect of a subchronic (4-week) exposure to low concentrations of toluene (40 or 80 parts per million, ppm) on the brain dopaminergic system has been examined in a rat model of Parkinson's disease. A unilateral lesion of the substantia nigra (SN) dopamine (DA) nerve cells was performed by injection of a low dose of 6-hydroxydopamine (6-OH DA). The peak activity of contralateral rotational behavior induced by apomorphine was significantly decreased after exposure to 80 ppm toluene. Analysis of the neostriatum and SN ipsilateral to the lesion revealed that toluene (80 ppm, but not 40 ppm) counteracted the 6-OH DA-induced reductions of DA tissue levels both within the SN and the neostriatum. Also the lesion-induced reduction of immunoreactivity for tyrosine hydroxylase (TH IR) in the neostriatum was partly counteracted by the toluene exposure (80 ppm). In conclusion, a subchronic exposure to low doses of toluene (80 ppm) leads to signs of reduced dysfunction of the nigrostriatal dopaminergic system after the neurotoxic treatment.

3,4-Dihydroxyphenylacetic Acid↗

CAPN11: A calpain with high mRNA levels in testis and located on chromosome 6.

Calpains are a superfamily of related proteins, some of which have been shown to function as calcium-dependent cysteine proteases. In mammals, eight different calpains have been identified. We report the identification of a new mammalian calpain gene, CAPN11. The predicted protein possesses the features typical of calpains including potential protease and calcium-binding domains. The CAPN11 mRNA exhibits a highly restricted tissue distribution with highest levels present in testis. Radiation hybrid mapping localized the gene to human chromosome 6, within a region mapped to p12. Phylogenetic analysis suggests that, in mammals, the predicted CAPN11 protein is most closely related to CAPN1 and CAPN2. However, of the calpain sequences available, the predicted CAPN11 sequence exhibits greatest homology to the chicken micro/m calpain. Thus CAPN11 may be the human orthologue of micro/m calpain. The discovery of this new calpain emphasizes the complexity of the calpain family, with members being distinguished on the basis of protease activity, calcium dependence, and tissue expression.

Amino Acid Sequence↗