| 1. |
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| 2. |
- Askmyr, Maria, et al.
(författare)
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Low-dose busulphan conditioning and neonatal stem cell transplantation preserves vision and restores hematopoiesis in severe murine osteopetrosis.
- 2009
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Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 37, s. 302-308
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Infantile malignant osteopetrosis is a fatal disease caused by lack of functional osteoclasts. In most of patients, TCIRG1, encoding a subunit of a proton pump essential for bone resorption, is mutated. Osteopetrosis leads to bone marrow failure and blindness due to optic nerve compression. Oc/oc mice have a deletion in Tcirg1 and die around 3 to 4 weeks, but can be rescued by neonatal stem cell transplantation (SCT) after irradiation conditioning. However, as irradiation of neonatal mice results in retinal degeneration, we wanted to investigate whether conditioning with busulphan prior to SCT can lead to preservation of vision and reversal of osteopetrosis in the oc/oc mouse model. MATERIALS AND METHODS: Pregnant dams were conditioned with busulphan and their litters transplanted with 1 x 10(6) normal lineage-depleted bone marrow cells intravenously or intraperitoneally. Mice were followed in terms of survival and engraftment level, as well as with peripheral blood lineage analysis, bone and eye histopathology and a visual-tracking drum test to assess vision. RESULTS: Busulphan at 15 mg/kg was toxic to oc/oc mice. However, six of seven oc/oc mice conditioned with busulphan 7.5 mg/kg survived past the normal lifespan with 10% engraftment, correction of the skeletal phenotype, and normalization of peripheral blood lineages. Busulphan, in contrast to irradiation, did not have adverse effects on the retina as determined by histopathology, and 8 weeks after transplantation control and oc/oc mice retained their vision. CONCLUSION: Low-dose busulphan conditioning and neonatal SCT leads to prolonged survival of oc/oc mice, reverses osteopetrosis and prevents blindness even at low engraftment levels.
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| 3. |
- Herlitz, Johan, et al.
(författare)
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Effect of metoprolol on chest pain in acute myocardial
- 1984
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Ingår i: British Heart Journal. - : BMJ Group. - 0007-0769. ; 51:4, s. 438-444
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Tidskriftsartikel (refereegranskat)abstract
- A total of 1395 patients aged 40 to 74 years were included in a double blind trial with the beta 1 selective blocker metoprolol in suspected acute myocardial infarction. Metoprolol was given intravenously (15 mg) as soon as possible after admission to hospital followed by 200 mg daily for three months. A placebo was given in the same manner. The severity of chest pain in the acute phase was calculated by recording the number of injections of analgesics given and the time from the start of blind treatment to the time when the last analgesic was given (duration of pain). The patients receiving metoprolol were given a lower mean number of injections of analgesics during the first four days and after randomisation than those receiving a placebo. The estimated duration of pain was shorter in the metoprolol group than in the placebo group. These effects were related to the initial heart rate, the initial systolic blood pressure, and the final site of the infarct as determined electrocardiographically. Thus metoprolol given in the acute phase of suspected or definite myocardial infarction appears to reduce the severity of chest pain.
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| 4. |
- Herlitz, Johan, et al.
(författare)
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Göteborg Metoprolol Trial : mortality and causes of death
- 1984
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 53:13, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- During the 3-month blind treatment period there were 40 deaths in the metoprolol group compared with 62 deaths in the placebo group (p = 0.024). During the first year (after 3 months the 2 groups were treated similarly) there were 64 deaths in the metoprolol group vs 93 in the placebo group (p = 0.017) and during 2 years 92 patients died in the metoprolol group vs 120 in the placebo group (p = 0.043). The relative incidence of different causes of death did not differ significantly between the 2 treatment groups, indicating that metoprolol reduced all causes of death to the same extent as its effect on overall mortality.
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| 5. |
- Herlitz, Johan, et al.
(författare)
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Göteborg Metoprolol Trial : design, patient characteristics and conduct
- 1984
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 53:13, s. 3D-8D
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Tidskriftsartikel (refereegranskat)abstract
- The Göteborg Metoprolol Trial was a double-blind, placebo-controlled, stratified trial aimed at evaluating the effect of the beta 1-selective blocker, metoprolol, in suspected acute myocardial infarction and during 2 years of follow-up. The primary end-point was 3-month mortality (blind treatment period). Secondary end-points were 2-year mortality, indirect signs of infarct size, chest pain, arrhythmias and tolerability. The entry criteria were fulfilled in 2,802 patients, 1,395 of whom were included in the trial. Treatment started as soon as possible after arrival in hospital with intravenous administration followed by oral treatment for 3 months. All patients were randomized 48 hours or less after estimated onset of infarction and 69% were randomized at 12 hours or less. The blind treatment had to be withdrawn in 19% of all randomized patients before the end of the 3-month follow-up.
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| 6. |
- Holmberg, Johan, et al.
(författare)
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Evaluating the psychometric characteristics of the Work-related Acceptance and Action Questionnaire (WAAQ) in a sample of healthcare professionals
- 2019
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Ingår i: Journal of Contextual Behavioral Science. - : Elsevier BV. - 2212-1447. ; 14, s. 103-107
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Tidskriftsartikel (refereegranskat)abstract
- The Work-related Acceptance and Action Questionnaire (WAAQ) has been developed to assess psychological flexibility in occupational settings. The aim of this study was to evaluate reliability and validity of the Swedish translation of WAAQ in a sample of 184 healthcare professionals. A principal component analysis supported a one-factor-solution, explaining 53.8% of the overall multivariate variability. WAAQ showed good internal consistency (Cronbach's alpha 0.85) and good test-retest reliability (ICC = 0.85). Validity was assessed by analysing the relationship between WAAQ and other work-related constructs. Spearman's rank correlations illustrated a significant negative relationship between WAAQ and perceived stress and a significant positive correlation with work engagement. Results from the study are consistent with previous studies on WAAQ, supporting the use of the Swedish translation of the instrument among healthcare professionals.
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| 7. |
- Holmberg, Johan, et al.
(författare)
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Psychological Flexibility and Its Relationship to Distress and Work Engagement Among Intensive Care Medical Staff
- 2020
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Intensive care settings place specific work-related demands on health care professionals that may elicit stress and negatively influence occupational health and work engagement. Psychological flexibility has emerged as a promising construct that could help explain variation in reported health. Understanding the role of psychological flexibility in occupational psychological health among intensive care medical staff may potentially guide the development of effective interventions. Thus, the present study evaluated the relationships between psychological flexibility (Work-related Acceptance and Action Questionnaire), distress (Perceived Stress Scale, General Health Questionnaire) and work engagement (Utrecht Work Engagement Scale) in a sample of 144 health care professionals from one adult (ICU, N = 98) and one pediatric (PICU, N = 46) intensive care unit. In addition to cross-sectional analyses, a subset of data (PICU, N = 46) was analyzed using a longitudinal design. Results illustrated that higher levels of distress were associated with lower levels of work engagement. Furthermore, psychological flexibility was related to greater work engagement, and psychological flexibility had a significant indirect effect on the relationship between distress and work engagement. Lastly, increased psychological flexibility over time corresponded with increased work engagement. Although tentative, the results suggest the importance of psychological flexibility for work engagement in health care professionals within intensive care settings.
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| 8. |
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| 9. |
- Bondestam, E, et al.
(författare)
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Pain assessment by patient and nurse in the early phase of acute myocardial infarction
- 1987
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Ingår i: Journal of Advanced Nursing. - : Wiley-Blackwell. - 0309-2402 .- 1365-2648. ; 12:6, s. 677-682
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Tidskriftsartikel (refereegranskat)abstract
- In 47 patients admitted to the coronary care unit (CCU) at Sahlgren's Hospital in Göteborg, Sweden, due to acute myocardial infarction (MI) the intensity of pain independently assessed by the patient and by the nurse on duty was evaluated during the first 24 hours in CCU. Pain was assessed according to a modified numerical rating scale graded from 0-10, where 0 meant no pain and 10 meant the most severe pain. A positive correlation between the patients’ and nurses’ assessments was found (r = 0-76; P < 0-001). However, the nurses under-estimated the patients’ pain in 23% of the situations and over-estimated it in 20%. Over-estimation was particularly found when heart rate and blood pressure increased. Many patients scoring their pain to fairly high degrees were not given pain-relieving treatment. Treatment with morphine did not cause substantial pain relief in a substantial number of patients. A significantly positive correlation was found between the patients’ and nurses’ assessments of pain, although underestimation as well as over-estimation occurred. A few patients with severe pain were not treated and when treatment was given it was often ineffective.
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| 10. |
- Gawlik, Kinga, et al.
(författare)
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Loss of Dystrophin and β-Sarcoglycan, Respectively, Significantly Exacerbates the Phenotype of Laminin α2 Chain-Deficient Animals.
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 184:3, s. 740-752
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Tidskriftsartikel (refereegranskat)abstract
- The adhesion molecule laminin α2 chain interacts with the dystrophin-glycoprotein complex, contributes to normal muscle function, and protects skeletal muscles from damage. Complete loss of the laminin α2 chain in mice results in a severe muscular dystrophy phenotype and death at approximately 3 weeks of age. However, it is not clear if the remaining members of the dystrophin-glycoprotein complex further protect laminin α2 chain-deficient skeletal muscle fibers from degeneration. Hence, we generated mice deficient in laminin α2 chain and dystrophin (dy(3K)/mdx) and mice devoid of laminin α2 chain and β-sarcoglycan (dy(3K)/Sgcb). Severe muscular dystrophy and a lack of nourishment inevitably led to massive muscle wasting and death in double-knockout animals. The dy(3K)/Sgcb mice were generally more severely affected than dy(3K)/mdx mice. However, both double-knockout strains displayed exacerbated muscle degeneration, inflammation, fibrosis, and reduced life span (5 to 13 days) compared with single-knockout animals. However, neither extraocular nor cardiac muscle was affected in double-knockout animals. Our results suggest that, although laminin α2 chain, dystrophin, and β-sarcoglycan are all part of the same adhesion complex, they have complementary, but nonredundant, roles in maintaining sarcolemmal integrity and protecting skeletal muscle fibers from damage. Moreover, the double-knockout mice could potentially serve as models in which to study extremely aggressive muscle-wasting conditions.
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| 11. |
- Grasselli, Robert K., et al.
(författare)
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Active centers, catalytic behavior, symbiosis and redox properties of MoV(Nb,Ta)TeO ammoxidation catalysts
- 2006
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Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 38:1-3, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Selective as well as waste forming active centers were defined for MoVNbTeO and MoVTaTeO catalysts in the ammoxidation of propane to acrylonitrile and all catalytic functionalities were assigned to specific elements at the respective active centers. Symbiosis between M1 and M2 phases of these catalysts was observed, with phase cooperation being more extensive in the Nb than Ta containing compositions. The difference in catalytic effectiveness arises most likely because contact and surface area exposure of the two respective, cooperating phase pairs are not equal. The M1 phase of the catalysts is reducible by propane and ammonia in the absence of dioxygen and is regenerable to its original, fully oxidized state by dioxygen (air). No structural collapse is observed even after 120 C3H8 + NH3 reduction pulses. The so induced reduction of the catalyst extends up to 70 layers deep. The product distribution over the first few pulses is very similar to that under catalytic conditions, supporting the concept that lattice oxygen is involved in the catalytic ammoxidation process. Therefore, the ammoxidation of paraffins is a redox process, as is of course the well-known olefin ammoxidation process.
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| 12. |
- Herlitz, Johan, et al.
(författare)
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Development of congestive heart failure after treatment with metoprolol in acute myocardial infarction
- 1984
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Ingår i: British Heart Journal. - : BMJ Group. - 0007-0769. ; 51:5, s. 539-544
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Tidskriftsartikel (refereegranskat)abstract
- In a double blind study of metoprolol in the treatment of suspected acute myocardial infarction 698 patients (study group) received metoprolol and 697 a placebo (control group). Metoprolol was given in an intravenous dose of 15 mg as soon as possible after admission to hospital followed by 50 g by mouth four times a day for two days and thereafter 100 mg twice a day for three months. A placebo was similarly given. Congestive heart failure occurred in a similar percentage of patients in both the study (27%) and the control groups (30%). Its severity was estimated by calculating the total dose of frusemide given during the first four days in hospital. Less frusemide was given to patients treated with metoprolol compared with those given a placebo in the total series. An appreciably lower total dose of frusemide was given to patients included in the trial less than or equal to 12 hours after the onset of pain and treated with metoprolol compared with a placebo, while no difference was seen among patients treated later. The initial heart rate, systolic blood pressure, and infarct site affected the results.
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| 13. |
- Herlitz, Johan, et al.
(författare)
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Effect of metoprolol on indirect signs of the size and severity of acute myocardial infarction
- 1983
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Ingår i: American Journal of Cardiology. - : Elsevier Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 51:8, s. 1282-1288
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Tidskriftsartikel (refereegranskat)abstract
- In a double-blind randomized trial, 1,395 patients with suspected acute myocardial infarction (MI) were investigated to evaluate the possibility of limiting indirect signs of the size and severity of acute MI with the beta1-selective adrenoceptor antagonist metoprolol. Metoprolol (15 mg) was given intravenously and followed by oral administration for 3 months (200 mg daily). Placebo was given in the same way. The size of the MI was estimated by heat-stable lactate dehydrogenase (LD[EC 1.1.1.27]) analyses and precordial electrocardiographic mapping. Lower maximal enzyme activities compared with placebo were seen in the metoprolol group (11.1 ± 0.5 μkat · liter−1)when the patient was treated within 12 hours of the onset of pain (13.3 ± 0.6 μkat · liter−1; n = 936; p = 0.009). When treatment was started later than 12 hours, no difference was found between the 2 groups. Enzyme analyses were performed in all but 20 patients (n = 1,375). Precordial mapping with 24 chest electrodes was performed in patients with anterior wall MI. The final total R-wave amplitude was higher and the final total Q-wave amplitude lower in the metoprolol group than in the placebo group. Patients treated with metoprolol ≤12 hours also showed a decreased need for furosemide, a shortened hospital stay, and a significantly reduced 1-year mortality compared with the placebo group, whereas no difference was observed among patients treated later on. After 3 months, however, there was a similar reduction in mortality among patients in whom therapy was started 12 hours and >12 hours after the onset of pain. The results support the hypothesis that intravenous metoprolol followed by oral treatment early in the course of suspected myocardial infarction can limit infarct size and improve longterm prognosis.
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| 14. |
- Herlitz, Johan, et al.
(författare)
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Effects of work and acute beta-receptor blockade on myocardial noradrenaline release in congestive cardiomyopathy
- 1979
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Ingår i: Clinical Cardiology. - : John Wiley & Sons, Inc. - 0160-9289 .- 1932-8737. ; 2:6, s. 424-430
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Tidskriftsartikel (refereegranskat)abstract
- Systemic hemodynamic changes and noradrenaline concentrations in coronary sinus blood were studied at rest and during work before and after acute beta-receptor blockade. Patients with congestive cardiomyopathy were compared to patients with primary valvular diseases and to healthy subjects. Noradrenaline concentrations were higher in coronary sinus blood than in arterial blood and increased after beta blockade and during work. Noradrenaline concentrations were more increased in patients with more pronounced myocardial failure and did not seem to separate patients with congestive cardiomyopathy from those with valvular disease. Patients with congestive cardiomyopathy showed a good hemodynamic tolerance toward acute beta blockade.
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| 15. |
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| 16. |
- Herlitz, Johan, et al.
(författare)
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Göteborg Metoprolol Trial : effects on arrhythmias
- 1984
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Ingår i: American Journal of Cardiology. - : Elsevier. - 0002-9149 .- 1879-1913. ; 53:13, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- During the initial hospitalization, ventricular fibrillation (VF) developed in 6 metoprolol-treated patients (0.9%) vs 17 placebo-treated patients (2.4%) after inclusion in the study (p = 0.035). There were 6 episodes of VF in the metoprolol group compared with 41 episodes in the placebo group (p less than 0.001). During the same period, 14 metoprolol-treated patients had treated ventricular tachycardia vs 26 placebo-treated patients (p = 0.076). Similar favorable results were found when the incidence of severe ventricular arrhythmias during the first rehospitalization within the 3-month double-blind treatment period was analyzed.
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| 17. |
- Herlitz, Johan, et al.
(författare)
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Tolerans för betablockad hos äldre
- 1982
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Ingår i: Hypertoni hos äldre. - : Almqvist & Wiksell. ; , s. 101-105
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Herlitz, Johan, et al.
(författare)
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Variability, prediction and prognostic significance of chest pain in acute myocardial infarction
- 1986
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Ingår i: Cardiology. - : S. Karger AG. - 0008-6312 .- 1421-9751. ; 73:1, s. 13-21
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Tidskriftsartikel (refereegranskat)abstract
- The variability of chest pain is described in 389 patients with acute myocardial infarction. Whereas 17% were free from severe pain after arrival in hospital, 11% required more than 10 analgesic injections. In 27% of the series analgesics were given more than 24 h after arrival in hospital. Predictors for the severity of chest pain were the rate-pressure product and degree of chest pain soon after arrival in hospital as well as electrocardiographic signs of myocardial infarction at entry. Patients with more severe chest pain had a higher 2-year mortality rate and a higher incidence of ventricular fibrillation and congestive heart failure during hospitalization.
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| 19. |
- Hjalmarson, A, et al.
(författare)
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The Göteborg metoprolol trial. Effects on mortality and morbidity in acute myocardial infarction
- 1983
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Ingår i: Circulation. - : SRDS. - 1539-3011. ; 67:suppl 1, s. 68-69
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Tidskriftsartikel (refereegranskat)abstract
- In the Göteborg Metoprolol Trial, 1395 patients with suspected acute myocardial infarction were, on admission, randomly allocated to double-blind treatment, 697 to placebo and 698 to metoprolol (15 mg i.v. + 200 mg/day) for 90 days. During this period, there were 62 deaths in the placebo group (8.9%) and 40 in the metoprolol group (5.7%), a mortality reduction of 36% (p less than 0.03). This effect persisted regardless of age, previous infarction or previous chronic beta blockade. All deaths were classified as cardiovascular. After 3 months, all patients were recommended open treatment with metoprolol, and the difference in mortality between the two groups was maintained after 1 year. Early institution of metoprolol (within 12 hours) influenced infarct development during the first 3 days (infarct diagnosis and indirect measures of infarct size). Metoprolol also reduced the incidence on fatal and nonfatal infarction during the next 4-90 days by 35%. Furthermore, fewer episodes of ventricular fibrillation were recorded in the metoprolol than in the placebo group (six vs 17 patients). The tolerance was judged to be very good. The same percentage of patients (19%) was withdrawn from the blind treatment in the two groups. Fewer patients in the metoprolol group used lidocaine, furosemide and analgesics. We conclude that metoprolol therapy instituted on admission in patients with suspected acute myocardial infarction reduced 3-month mortality and exerted beneficial clinical effects.
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| 20. |
- Hjalmarson, Å, et al.
(författare)
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Effect on mortality of metoprolol in acute myocardial infarction
- 1981
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Ingår i: The Lancet. - : The Lancet Publishing Group. - 0140-6736 .- 1474-547X. ; 318:8251, s. 823-827
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Tidskriftsartikel (refereegranskat)abstract
- The effect of metoprolol on mortality was compared with that of placebo in a double-blind randomised trial in patients with definite or suspected acute myocardial infarction. Treatment with metoprolol or placebo started as soon as possible after the patient's arrival in hospital and was continued for 90 days. Metoprolol was given as a 15 mg intravenous dose followed by oral administration of 100 mg twice daily. 1395 patients (697 on placebo and 698 on metoprolol) were included in the trial. Definite acute myocardial infarction developed in 809 and probable infarction in 162. Patients were allocated to various risk groups and within each group patients were randomly assigned to treatment with metoprolol or placebo. There were 62 deaths in the placebo group (8·9%) and 40 deaths in the metoprolol group (5·7%), a reduction of 36% (p<0·03). Mortality rates are given according to the treatment group to which the patients were initially randomly allocated.
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| 21. |
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| 22. |
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| 23. |
- Holmberg, Johan, et al.
(författare)
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A study of the functionalities of the phases in Mo-V-Nb-Te oxides for propane ammoxidation
- 2003
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Ingår i: Topics in Catalysis. - 1572-9028. ; 23:1-4, s. 55-63
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Tidskriftsartikel (refereegranskat)abstract
- Catalysts belonging to the Mo-V-Nb-Te-O system have been prepared with both a slurry method and hydrothermal synthesis and were tested for propane and propylene ammoxidation to acrylonitrile. All samples were characterized with BET, XRD, ICP and XPS. The catalysts were found to consist of three phases, to which activity and selectivity correlations were made. The results indicate that both an orthorhombic phase and a hexagonal phase are needed to have an active and selective catalyst. The orthorhombic phase is the most active for propane conversion although less selective than the hexagonal phase for the conversion of formed propylene to acrylonitrile.
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| 24. |
- Holmberg, Johan, et al.
(författare)
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Catalytic behaviour of M1, M2, and M1/M2 physical mixtures of the Mo-V-Nb-Te-oxide system in propane and propene ammoxidation
- 2004
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Ingår i: Applied Catalysis A: General. - : Elsevier BV. - 0926-860X. ; 270:1-2, s. 121-134
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Tidskriftsartikel (refereegranskat)abstract
- Essentially pure orthorhombic M1 and pseudo-hexagonal M2 phases were prepared using the precursor method. Consistent with literature the M1 phase was shown to be effective for propane ammoxidation to acrylonitrile while the M2 phase was essentially inert for propane activation. Both phases convert propene efficiently to acrylonitrile. Both phases show a significant selectivity dependence on the ammonia and oxygen concentrations in the feed, revealing thereby additional insights into the reaction mechanism. Physical mixtures of the two separately prepared phases exhibited symbiosis in the ammoxidation of propane when finally divided (similar to5 mum), thoroughly mixed and brought into intimate contact with each other. Acrylonitrile yields significantly higher than those obtained with the M1 phase alone were demonstrated with a 50 wt.% M1/50 wt.% M2 physical mixture having a corresponding Surface area ratio of about 4:1. The phase cooperation effect is particularly large at high propane conversions and non-existent when the particle size of the phases is too large (e.g. >250 mum) and the inter-particle contact is poor. Published by Elsevier B.V.
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| 25. |
- Holmberg, Johan K
(författare)
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Gain-of-function induced defects by PITX2 in eye and limb development
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- My research has been focused on eye and limb development with regard to the transcription factor PITX2. In the first paper we present an Axenfeld-Rieger syndrome PITX2 gain-of-function eye mouse model. Axenfeld-Rieger syndrome is a rare autosomal disorder affecting the development of eyes, teeth and abdomen. The eye defects consist of anomalies in the anterior segment. In addition, almost 50% of Axenfeld-Rieger syndrome patients develop glaucoma, the leading cause of vision loss worldwide. The mouse model faithfully recapitulated these eye symptoms. The next paper describes a forelimb phenotype due to a brief pulse of PITX2 overexpression in the forelimbs during embryogenesis. This overexpression interferes with tendon morphogenesis resulting in severe bone malformations, which in turn twist the forelimb and makes it non-supportable. The mechanisms behind limb tendon development and positioning are largely unknown, which makes this study a valuable resource for further studies on the development of the musculoskeletal system. In the third paper we compare the phenotypic outcome of PITX2 overexpression between three different mouse strains to study the effect of strain specific modifier genes. We observe both gain-of- and loss-of-function phenotypes, which indicate existence of strain specific genes working in concert with PITX2 during eye and limb development. To put these papers in a context I have aimed at gaining a deeper insight into the role of PITX2 in the development of eye and limb, and to increase the understanding of the pathophysiology of the eye defects associated with Axenfeld-Rieger syndrome.
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| 26. |
- Holmberg, Johan K, et al.
(författare)
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Laminin-211 in skeletal muscle function.
- 2012
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Ingår i: Cell Adhesion and Migration. - 1933-6918. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- A chain is no stronger than its weakest link is an old idiom that holds true for muscle biology. As the name implies, skeletal muscle's main function is to move the bones. However, for a muscle to transmit force and withstand the stress that contractions give rise to, it relies on a chain of proteins attaching the cytoskeleton of the muscle fiber to the surrounding extracellular matrix. The importance of this attachment is illustrated by a large number of muscular dystrophies caused by interruption of the cytoskeletal-extracellular matrix interaction. One of the major components of the extracellular matrix is laminin, a heterotrimeric glycoprotein and a major constituent of the basement membrane. It has become increasingly apparent that laminins are involved in a multitude of biological functions, including cell adhesion, differentiation, proliferation, migration and survival. This review will focus on the importance of laminin-211 for normal skeletal muscle function.
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| 27. |
- Holmberg, Johan K, et al.
(författare)
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Laminin α2 Chain-Deficiency is Associated with microRNA Deregulation in Skeletal Muscle and Plasma.
- 2014
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 6:Jul 3
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Tidskriftsartikel (refereegranskat)abstract
- microRNAs (miRNAs) are widespread regulators of gene expression, but little is known of their potential roles in congenital muscular dystrophy type 1A (MDC1A). MDC1A is a severe form of muscular dystrophy caused by mutations in the gene encoding laminin α2 chain. To gain insight into the pathophysiological roles of miRNAs associated with MDC1A pathology, laminin α2 chain-deficient mice were evaluated by quantitative PCR. We demonstrate that expression of muscle-specific miR-1, miR-133a, and miR-206 is deregulated in laminin α2 chain-deficient muscle. Furthermore, expression of miR-223 and miR-21, associated with immune cell infiltration and fibrosis, respectively, is altered. Finally, we show that plasma levels of muscle-specific miRNAs are markedly elevated in laminin α2 chain-deficient mice and partially normalized in response to proteasome inhibition therapy. Altogether, our data suggest important roles for miRNAs in MDC1A pathology and we propose plasma levels of muscle-specific miRNAs as promising biomarkers for the progression of MDC1A.
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| 28. |
- Holmberg, Johan K, et al.
(författare)
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PITX2 gain-of-function induced defects in mouse forelimb development.
- 2008
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Ingår i: BMC Developmental Biology. - 1471-213X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Limb development and patterning originate from a complex interplay between the skeletal elements, tendons, and muscles of the limb. One of the genes involved in patterning of limb muscles is the homeobox transcription factor Pitx2 but its role in forelimb development is uncharacterized. Pitx2 is expressed in the majority of premature presumptive forelimb musculature at embryonic day 12.5 and then maintained throughout embryogenesis to adult skeletal muscle. RESULTS: To further study the role of Pitx2 in forelimb development we have generated transgenic mice that exhibit a pulse of PITX2 over-expression at embryonic day 13.5 and 14.5 in the developing forelimb mesenchyme. These mice exhibit a distal misplacement of the biceps brachii insertion during embryogenesis, which twists the forelimb musculature resulting in severe skeletal malformations. The skeletal malformations have some similarities to the forearm deformities present in Leri-Weill dyschondrosteosis. CONCLUSION: Taken together, the tendon, muscle, and bone anomalies further support a role of Pitx2 in forelimb development and may also shed light on the interaction between the skeletal elements and muscles of the limb during embryogenesis.
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| 29. |
- Holmberg, Johan, et al.
(författare)
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Old Moving Groups
- 2002
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Ingår i: Modes of Star Formation and the Origin of Field Populations, ASP Conference Proceedings.. - 1583811281 ; 285, s. 188-194
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Konferensbidrag (refereegranskat)
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| 30. |
- Hovgren, K, et al.
(författare)
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Initial pain course and delay to hospital admission in relation to myocardial infarct size
- 1988
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Ingår i: Heart & Lung. - : Mosby, Inc.. - 0147-9563 .- 1527-3288. ; 17, s. 274-280
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Tidskriftsartikel (refereegranskat)abstract
- In 47 patients admitted to the coronary care unit (CCU) at Sahlgren's Hospital because of acute myocardial infarction (MI), we evaluated the intensity of pain before admission and during the first 24 hours in the CCU and the delay time between the onset of symptoms and the decision to go to the hospital. Pain was assessed according to a modified visual analogue scale graded from 0 to 10, where 0 meant no pain and 10 meant the most severe pain. Patients generally scored their maximal pain before admission higher than their pain in the CCU. The maximal pain before admission did not seem to differ between patients with larger and smaller infarcts, estimated from maximal serum enzyme activity, whereas patients with larger infarcts tended to have more intensive pain in the hospital despite consuming more analgesics during the first 3 hours and the first 24 hours in the CCU. The time between onset of symptoms and decision to go to the hospital was not influenced by the intensity of pain before admission, but patients with larger infarcts made their decision much faster than those with smaller infarcts. In conclusion, infarct size, a major determinant of the initial prognosis, appeared to influence the initial pain course in the CCU and to markedly affect the delay time between onset of symptoms and the decision to seek medical care.
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| 31. |
- Häger, Mattias, et al.
(författare)
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Cib2 binds integrin a7Bb1D and is reduced in laminin a2 chain deficient muscular dystrophy
- 2008
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 283:36, s. 24760-24769
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the gene encoding laminin alpha 2 chain cause congenital muscular dystrophy type 1A. In skeletal muscle, laminin alpha 2 chain binds at least two receptor complexes: the dystrophin-glycoprotein complex and integrin alpha 7 beta 1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin alpha 2 chain-deficient mouse limb muscle. One of the down-regulated genes encodes a protein called Cib2 (calcium-and integrin-binding protein 2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin alpha IIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin alpha 7 beta 1-binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle, Cib2 colocalizes with the integrin alpha 7B subunit at the sarcolemma and at the neuromuscular and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium-binding protein that interacts with integrin alpha 7B beta 1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin alpha 7B beta 1D signaling in skeletal muscle.
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| 32. |
- Häggblad, Robert, et al.
(författare)
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Substituted Mo-V(Ti)-Te(Ce)-oxide M2 catalysts for propene ammoxidation
- 2008
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Ingår i: Topics in Catalysis. - : Springer Science and Business Media LLC. - 1572-9028 .- 1022-5528. ; 50:1-4, s. 52-65
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Tidskriftsartikel (refereegranskat)abstract
- One of the most effective propane to acrylonitrile ammoxidation catalyst is comprised of the two phases M1 (orthorhombic) Mo7.5V1.5NbTeO29 and M2 (pseudo-hexagonal) Mo4V2Te2O20. Under reaction conditions, the two phases work in symbiosis with each other where M1 is the paraffin activating component and M2 is the olefin activating component. Since the catalytic improvement of either phase should result in an enhancement of the overall acrylonitrile yield, controlled substitution of certain elements in either or both phases might result in the desired improvement. Our current study concentrates on the partial substitutions of V with Ti and Te with Ce in the M2 phase. Ti substitution results in a considerable propene activity improvement, whereas the selectivity to acrylonitrile is unaffected. Substitution with Ce, on the contrary, substantially improves the selectivity to acrylonitrile. Also, a minor improvement of the activity is notable. The acrylonitrile selectivity improvement is a result of better NH3 utilization and comes at the expense of reduced acrolein make. XRD reveals that all of the substituted compositions retain the M2 structure and essentially are monophasic. XANES recordings show for the bulk that the Mo is 6+, the V is 4+, or 4+ and 5+ when Ce is present, the Ti is 4+, the Ce is 3+, and the Te 4+ with some 6+ also present. According to the ESR data, in the M2 with Ce (7Te/3Ce) only 21% of the V is 4+, the remainder being 5+, which tentatively can be explained by the existence of some cation vacancies in the hexagonal channels. HRTEM imaging reveals little if any differences between the materials, all have the typical pseudo-hexagonal habit of the M2 phase and expose a 1-2 nm thick surface layer without any apparent long-range ordering. XPS data show that all catalysts, including the base, are highly enriched at the surface with Te at the expense of other metals. The 7Te/3Ce composition exhibits also substantial Ce surface enrichment. Moreover, the valences of the cations at the surface differ from the bulk in that for all fresh catalysts V is 5+ and Te is 6+ on the surface. Characterization by XPS of catalysts used in propene ammoxidation, reveals reduction of Te and, except when Ce is present, also Mo. Therefore, it might be inferred that the surfaces of the catalysts studied here are comprised essentially of one or a few monolayers of TeMoO or TeCeMoO on an interacting M2 crystalline base.
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| 33. |
- Körner, Zandra, et al.
(författare)
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Bortezomib Partially Improves Laminin α2 Chain-Deficient Muscular Dystrophy.
- 2014
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 184:5, s. 1518-1528
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Tidskriftsartikel (refereegranskat)abstract
- Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted.
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| 34. |
- Li, Shuijie, et al.
(författare)
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Impaired oxygen-sensitive regulation of mitochondrial biogenesis within the von Hippel–Lindau syndrome
- 2022
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Ingår i: Nature Metabolism. - : Nature Publishing Group. - 2522-5812. ; 4:6, s. 739-758
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondria are the main consumers of oxygen within the cell. How mitochondria sense oxygen levels remains unknown. Here we show an oxygen-sensitive regulation of TFAM, an activator of mitochondrial transcription and replication, whose alteration is linked to tumours arising in the von Hippel–Lindau syndrome. TFAM is hydroxylated by EGLN3 and subsequently bound by the von Hippel–Lindau tumour-suppressor protein, which stabilizes TFAM by preventing mitochondrial proteolysis. Cells lacking wild-type VHL or in which EGLN3 is inactivated have reduced mitochondrial mass. Tumorigenic VHL variants leading to different clinical manifestations fail to bind hydroxylated TFAM. In contrast, cells harbouring the Chuvash polycythaemia VHLR200W mutation, involved in hypoxia-sensing disorders without tumour development, are capable of binding hydroxylated TFAM. Accordingly, VHL-related tumours, such as pheochromocytoma and renal cell carcinoma cells, display low mitochondrial content, suggesting that impaired mitochondrial biogenesis is linked to VHL tumorigenesis. Finally, inhibiting proteolysis by targeting LONP1 increases mitochondrial content in VHL-deficient cells and sensitizes therapy-resistant tumours to sorafenib treatment. Our results offer pharmacological avenues to sensitize therapy-resistant VHL tumours by focusing on the mitochondria.
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| 35. |
- Milosevic, Jelena, et al.
(författare)
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PPM1D is a neuroblastoma oncogene and therapeutic target in childhood neural tumors
- 2020
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Majority of cancers harbor alterations of the tumor suppressor TP53. However, childhood cancers, including unfavorable neuroblastoma, often lack TP53 mutations despite frequent loss of p53 function, suggesting alternative p53 inactivating mechanisms.Here we show that p53-regulating PPM1D at chromosome 17q22.3 is linked to aggressive tumors and poor prognosis in neuroblastoma. We identified that WIP1-phosphatase encoded by PPM1D, is activated by frequent segmental 17q-gain further accumulated during clonal evolution, gene-amplifications, gene-fusions or gain-of-function somatic and germline mutations. Pharmacological and genetic manipulation established WIP1 as a druggable target in neuroblastoma. Genome-scale CRISPR-Cas9 screening demonstrated PPM1D genetic dependency in TP53 wild-type neuroblastoma cell lines, and shRNA PPM1D knockdown significantly delayed in vivo tumor formation. Establishing a transgenic mouse model overexpressing PPM1D showed that these mice develop cancers phenotypically and genetically similar to tumors arising in mice with dysfunctional p53 when subjected to low-dose irradiation. Tumors include T-cell lymphomas harboring Notch1-mutations, Pten-deletions and p53-accumulation, adenocarcinomas and PHOX2B-expressing neuroblastomas establishing PPM1D as a bona fide oncogene in wtTP53 cancer and childhood neuroblastoma. Pharmacological inhibition of WIP1 suppressed the growth of neural tumors in nude mice proposing WIP1 as a therapeutic target in neural childhood tumors.
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| 36. |
- Pellinen, T., et al.
(författare)
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Fibroblast subsets in non-small cell lung cancer: Associations with survival, mutations, and immune features
- 2023
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Ingår i: Jnci-Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 115:1, s. 71-82
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Tidskriftsartikel (refereegranskat)abstract
- Background Cancer-associated fibroblasts (CAFs) are molecularly heterogeneous mesenchymal cells that interact with malignant cells and immune cells and confer anti- and protumorigenic functions. Prior in situ profiling studies of human CAFs have largely relied on scoring single markers, thus presenting a limited view of their molecular complexity. Our objective was to study the complex spatial tumor microenvironment of non-small cell lung cancer (NSCLC) with multiple CAF biomarkers, identify novel CAF subsets, and explore their associations with patient outcome. Methods Multiplex fluorescence immunohistochemistry was employed to spatially profile the CAF landscape in 2 population-based NSCLC cohorts (n = 636) using antibodies against 4 fibroblast markers: platelet-derived growth factor receptor-alpha (PDGFRA) and -beta (PDGFRB), fibroblast activation protein (FAP), and alpha-smooth muscle actin (alpha SMA). The CAF subsets were analyzed for their correlations with mutations, immune characteristics, and clinical variables as well as overall survival. Results Two CAF subsets, CAF7 (PDGFRA-/PDGFRB+/FAP+/alpha SMA+) and CAF13 (PDGFRA+/PDGFRB+/FAP-/alpha SMA+), showed statistically significant but opposite associations with tumor histology, driver mutations (tumor protein p53 [TP53] and epidermal growth factor receptor [EGFR]), immune features (programmed death-ligand 1 and CD163), and prognosis. In patients with early stage tumors (pathological tumor-node-metastasis IA-IB), CAF7 and CAF13 acted as independent prognostic factors. Conclusions Multimarker-defined CAF subsets were identified through high-content spatial profiling. The robust associations of CAFs with driver mutations, immune features, and outcome suggest CAFs as essential factors in NSCLC progression and warrant further studies to explore their potential as biomarkers or therapeutic targets. This study also highlights multiplex fluorescence immunohistochemistry-based CAF profiling as a powerful tool for the discovery of clinically relevant CAF subsets.
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| 37. |
- Richterova, A, et al.
(författare)
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Goteborg Metoprolol Trial : effects on chest pain
- 1984
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Ingår i: American Journal of Cardiology. - : Excerpta Medica, Inc.. - 0002-9149 .- 1879-1913. ; 53:13, s. 32-36
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Tidskriftsartikel (refereegranskat)abstract
- The effect of metoprolol on chest pain was compared with that of placebo in all randomized patients. The pain score before and 15 minutes after the injection of trial medication was registered and a reduction in chest pain was observed in the metoprolol group. Increasing chest pain after blind injection was observed in only 16 and 9 patients from the placebo and metoprolol groups, respectively. Comparison with the placebo as well as detailed analysis of clinical data revealed that in these patients the increasing pain could not be explained by coronary spasm evoked by beta-blockade. Similarly, metoprolol did not exhibit any unfavorable effect on the 14 patients who were withdrawn (together with the 28 patients given placebo) from blind treatment due to angina pectoris. Either metoprolol does not induce coronary vasospasm or spasm does not play a role in these patients with definite and suspected acute myocardial infarction as well as unstable angina pectoris. Metoprolol reduced the need for analgesics during the first 4 days and shortened the duration of pain. The effects were similar in patients with early and late treatment, but may depend on initial heart rate, blood pressure and site of infarction.
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| 38. |
- Risenfors, M, et al.
(författare)
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Effect on early intravenous rt-PA on infarct size estimated from serum enzyme activity : results from the TEAHAT Study
- 1991
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 734:suppl 1, s. 11-18
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Tidskriftsartikel (refereegranskat)abstract
- In 319 patients who participated in a double-blind trial to evaluate the effect of early rt-PA administration compared to placebo in suspected acute myocardial infarction, infarct size was assessed from analyses of serum activity of lactate dehydrogenase isoenzyme 1 (LD 1). Treatment was always started less than 3 h after the onset of symptoms, with one-third of the patients' treatment being initiated outside the hospital. The maximum activity of LD 1 was reduced by 32%, from 13.3 mu kat l-1 in placebo to 9.0 mu kat l-1 in rt-PA treated patients (P = 0.001). A reduction in LD-1 activity after rt-PA treatment was restricted to patients with ST-elevation in the initial electrocardiogram, and was more pronounced in patients with previous ischaemic heart disease, above median age, and in those with a shorter delay in initiation of treatment. We conclude that very early intravenous treatment with rt-PA limits indirect signs of infarct size. The effect appears to be restricted to patients with ST-segment elevation in their initial electrocardiogram.
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| 39. |
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| 40. |
- Rydén, L, et al.
(författare)
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A Double-Blind Trial of Metoprolol in Acute Myocardial Infarction : Effects on Ventricular Tachyarrhythmias
- 1983
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 308:11, s. 614-618
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Tidskriftsartikel (refereegranskat)abstract
- During a double-blind trial in which patients with suspected myocardial infarction received metoprolol or placebo, we analyzed the occurrence of ventricular tachyarrhythmias. Metoprolol (15 mg intravenously) was given as soon as possible after admission, and thereafter 200 mg was given daily for three months. Antiarrhythmic drugs were given only for ventricular fibrillation and sustained ventricular tachycardia (greater than 60 beats per second). Definite acute myocardial infarction developed in 809 of the 1395 participants, and probable infarction in 162. Metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia. However, there were 17 cases of ventricular fibrillation in the placebo group (697 patients) and only 6 in the metoprolol group (698 patients, P less than 0.05). During the hospital stay significantly fewer patients receiving metoprolol (16) than placebo (38) (P less than 0.01) required lidocaine. In a separate analysis of 145 patients, metoprolol did not influence the occurrence of premature ventricular contractions or short bursts of ventricular tachycardia during the first 24 hours of treatment. Despite a lack of effect on less serious ventricular tachyarrhythmias, metoprolol had a prophylactic effect against ventricular fibrillation in acute myocardial infarction.
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| 41. |
- Strömsöe, Anneli, 1969, et al.
(författare)
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Education in cardiopulmonary resuscitation in Sweden and its clinical consequences.
- 2010
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 81:2, s. 211-6
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Tidskriftsartikel (refereegranskat)abstract
- To describe the use of cardiopulmonary resuscitation (CPR) training programmes in Sweden for 25 years and relate those to changes in the percentage of patients with out of hospital cardiac arrest (OHCA) who receive bystander CPR.
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| 42. |
- Swärd, Karl, et al.
(författare)
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Identification of the intermediate filament protein synemin/SYNM as a target of myocardin family coactivators
- 2019
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Ingår i: American Journal of Physiology - Cell Physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 317:6, s. 1128-1142
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Tidskriftsartikel (refereegranskat)abstract
- Myocardin (MYOCD) is a critical regulator of smooth muscle cell (SMC) differentiation, but its transcriptional targets remain to be exhaustively characterized, especially at the protein level. Here we leveraged human RNA and protein expression data to identify novel potential MYOCD targets. Using correlation analyses we found several targets that we could confirm at the protein level, including SORBS1, SLMAP, SYNM, and MCAM. We focused on SYNM, which encodes the intermediate filament protein synemin. SYNM rivalled smooth muscle myosin (MYH11) for SMC specificity and was controlled at the mRNA and protein levels by all myocardin-related transcription factors (MRTFs: MYOCD, MRTF-A/MKL1, and MRTF-B/MKL2). MRTF activity is regulated by the ratio of filamentous to globular actin, and SYNM was accordingly reduced by interventions that depolymerize actin, such as latrunculin treatment and overexpression of constitutively active cofilin. Many MRTF target genes depend on serum response factor (SRF), but SYNM lacked SRF-binding motifs in its proximal promoter, which was not directly regulated by MYOCD. Furthermore, SYNM resisted SRF silencing, yet the time course of induction closely paralleled that of the SRF-dependent target gene ACTA2. SYNM was repressed by the ternary complex factor (TCF) FLI1 and was increased in mouse embryonic fibroblasts lacking three classical TCFs (ELK1, ELK3, and ELK4). Imaging showed colocalization of SYNM with the intermediate filament proteins desmin and vimentin, and MRTF-A/MKL1 increased SYNM-containing intermediate filaments in SMCs. These studies identify SYNM as a novel SRF-independent target of myocardin that is abundantly expressed in all SMCs.
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| 43. |
- Södersten, Erik, et al.
(författare)
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A comprehensive map coupling histone modifications with gene regulation in adult dopaminergic and serotonergic neurons
- 2018
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Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The brain is composed of hundreds of different neuronal subtypes, which largely retain their identity throughout the lifespan of the organism. The mechanisms governing this stability are not fully understood, partly due to the diversity and limited size of clinically relevant neuronal populations, which constitute a technical challenge for analysis. Here, using a strategy that allows for ChIP-seq combined with RNA-seq in small neuronal populations in vivo, we present a comparative analysis of permissive and repressive histone modifications in adult midbrain dopaminergic neurons, raphe nuclei serotonergic neurons, and embryonic neural progenitors. Furthermore, we utilize the map generated by our analysis to show that the transcriptional response of midbrain dopaminergic neurons following 6-OHDA or methamphetamine injection is characterized by increased expression of genes with promoters dually marked by H3K4me3/H3K27me3. Our study provides an in vivo genome-wide analysis of permissive/repressive histone modifications coupled to gene expression in these rare neuronal subtypes.
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