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| 2. |
- Bodén, Ida, 1977-, et al.
(författare)
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Non-invasive identification of melanoma with near-infrared and skin impedance spectroscopy
- 2013
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Ingår i: Skin research and technology. - : John Wiley & Sons. - 0909-752X .- 1600-0846. ; 19:1, s. e473-e478
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Tidskriftsartikel (refereegranskat)abstract
- Background/purpose: An early diagnosis of cutaneous malignant melanoma is of high importance for good prognosis. An objective, non-invasive instrument could improve the diagnostic accuracy of melanoma and decrease unnecessary biopsies. The aim of this study was to investigate the use of Near infrared and skin impedance spectroscopy in combination as a tool to distinguish between malignant and benign skin tumours.Methods: Near infrared and skin impedance spectra were collected in vivo on 50 naevi or suspect melanomas prior to excision. Received data was analysed with multivariate techniques and the results were compared to histopathology analyses of the tumours. A total of 12 cutaneous malignant melanomas, 19 dysplastic naevi and 19 benign naevi were included in the study.Results: The observed sensitivity and specificity of the proposed method were 83% and 95%, respectively, for malignant melanoma.Conclusions: The results indicate that the combination of near infrared and skin impedance spectroscopy is a promising tool for non-invasive diagnosis of suspect cutaneous malignant melanomas.
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| 3. |
- Ekman, Bertil, et al.
(författare)
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A dose titration model for recombinant GH substitution aiming at normal plasma concentrations of IGF-I in hypopituitary adults
- 2002
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:1, s. 49-57
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate a dose titration model for recombinant human GH substitution in adult patients with GH deficiency, aiming at normal plasma levels of IGF-I.DESIGN AND METHODS: Eighteen patients participated and a start dose of 0.17 mg GH/day was used except by two men who started with 0.33 mg/day. To demonstrate a clear GH effect the patients were first titrated, with steps of 0.17 mg GH/day every 6-8 weeks, to IGF-I levels in the upper range of age-adjusted reference values. The GH dose was then reduced 1 dose step and kept for a further 6 months. For comparison we investigated 17 healthy control subjects.RESULTS: Plasma IGF-I was increased after 2 weeks on the start dose and did not increase further for up to 8 weeks. Women had significantly lower GH sensitivity than men measured as net increment of IGF-I on the start dose of GH. GH sensitivity was not changed by age. The plasma IGF-I levels increased from 76.3+/-47.0 (s.d.) to 237+/-97 microg/l at the end of the study (P<0.001), and similar IGF-I levels were obtained in both sexes. The maintenance median GH dose was 0.33 mg/day in males and 0.83 mg/day in females (P=0.017). The GH dose correlated negatively with age in both sexes. Body weight, very low density triglycerides, lipoprotein(a) (Lp(a)), and fasting insulin increased, whereas insulin sensitivity index (QUICKI) decreased significantly. In comparison with the controls, the patients had lower fasting blood glucose, fasting insulin and Lp(a) levels at baseline, but these differences disappeared after GH substitution. The two groups had equal insulin sensitivity (QUICKI), but 2 h oral glucose tolerance test values of blood glucose and insulin were significantly higher in the patients at the end of the study.CONCLUSIONS: In conclusion our data suggest that the starting dose of GH substitution and the dose titration steps should be individualised according to GH sensitivity (gender) and the IGF-I level aimed for (age). The reduced insulin sensitivity induced by GH substitution could be viewed as a normalisation if compared with control subjects.
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| 4. |
- Ekman, Bertil, et al.
(författare)
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Circulating IGF-I concentrations are low and not correlated to glycaemic control in adults with type 1 diabetes
- 2000
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 143:4, s. 505-510
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To study plasma concentrations of insulin-like growth factor-I (IGF-I) in adults with type 1 diabetes (IDDM) in comparison with a reference population, and the influence of glycaemic control, dose of insulin, and sex on the concentration of circulating IGF-I in IDDM.DESIGN AND METHODS: Patients with type 1 diabetes were recruited consecutively from our outpatient diabetes unit. In all, 79 men and 55 women aged 20-60 years with a disease duration >/=6 years (range 6-51 years) took part in the study. A reference population of 80 men and 83 women aged 20-60 years was randomly obtained from the population registry. IGF-I was measured with radioimmunoassay after acid-ethanol extraction.RESULTS: Mean +/- s. d. values of IGF-I were lower in patients with diabetes (146+/-66 microg/l) than in controls (238+/-83 microg/l, P<0.001). Those with diabetes had lower IGF-I concentrations in all age groups and the differences were highly significant in all decades except in women aged 50-59 years. IGF-I was negatively correlated with age in patients and controls. No correlation was found between IGF-I and glycaemic control measured as haemoglobin A(1c) (HbA(1c)) in the patients. IGF-I was positively associated with the dose of insulin/kg body weight in male patients independently of age, HbA(1c) and body mass index (P<0.03), but not in female patients (P=0.14).CONCLUSIONS: Our data show that IGF-I concentrations are low in adult patients with type 1 diabetes with a disease duration >/=6 years, independently of glycaemic control. This suggests that subcutaneous insulin substitution is inadequate to normalize circulating IGF-I concentrations in patients without endogenous insulin secretion.
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| 5. |
- Ekman, Bertil, et al.
(författare)
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Individualized growth hormone substitution with normalized IGF-I levels does not stimulate the renin–angiotensin–aldosterone system
- 2002
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 57:4, s. 473-479
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Tidskriftsartikel (refereegranskat)abstract
- objective To study the effects of individualized recombinant GH substitution, aiming at normal circulating IGF-I levels, in GH-deficient adults on blood pressure, the renin–angiotensin–aldosterone system (RAAS), natriuretic peptides and urine free cortisol.study design Open study with control group. The patients were titrated in dose steps of 0·17 mg GH/day every 6–8 weeks until an IGF-I level around the mean + 1 SD was attained (Tmax). After another month the dose was reduced by 0·17 mg (minimum dose 0·17 mg/day) to produce IGF-I levels at or slightly below the age-related mean (Tend), and this maintenance dose was held constant for 6 months.subjects Eighteen patients (11 males and seven females) with GH deficiency participated. For comparison we also prospectively evaluated 17 matched control subjects.measurements Blood pressure and heart rate, circulating levels of IGF-I, plasma renin activity (PRA), immunoreactive active renin (IRR), angiotensin II, aldosterone, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and 24-h urine aldosterone and urine free cortisol levels.results Blood pressure was unchanged by GH substitution but heart rate increased significantly (P < 0·03). PRA was elevated on the highest GH dose (Tmax) compared to baseline (P < 0·01), but returned to baseline and levels of controls at Tend. Four patients developed transient oedema and tended to have higher PRA levels than the rest of the subjects (P = 0·09). The circulating levels of IRR, angiotensin II, aldosterone, BNP and 24-h urine aldosterone and urine free cortisol levels were unchanged by GH substitution, and did not differ from the levels in the control subjects. Baseline ANP levels in the patients were lower than in the controls (P < 0·01), but increased after GH substitution (P < 0·01) to levels found in with the controls.conclusions We found no major changes of the variables in the circulating renin–angiotensin–aldosterone system and a normalization of atrial natriuretic peptide when an individualized dose of GH was titrated to near-normal IGF-I levels.
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| 6. |
- Gummesson, Bertil, 1977, et al.
(författare)
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A Proximal Promoter Element Required for Positive Transcriptional Control by Guanosine Tetraphosphate and DksA Protein during the Stringent Response
- 2013
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Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 288:29, s. 21055-21064
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Tidskriftsartikel (refereegranskat)abstract
- The alarmone guanosine tetraphosphate (ppGpp) acts as both a positive and a negative regulator of gene expression in the presence of DksA, but the underlying mechanisms of this differential control are unclear. Here, using uspA hybrid promoters, we show that an AT-rich discriminator region is crucial for positive control by ppGpp/DksA. The AT-rich discriminator makes the RNA polymerase-promoter complex extremely stable and therefore easily saturated with RNA polymerase. A more efficient transcription is achieved when the RNA polymerase-promoter complex is destabilized with ppGpp/DksA. We found that exchanging the AT-rich discriminator of uspA with the GC-rich rrnB-P1 discriminator made the uspA promoter negatively regulated by ppGpp/DksA both in vivo and in vitro. In addition, the GC-rich discriminator destabilized the RNA polymerase-promoter complex, and the effect of ppGpp/DksA on the kinetic properties of the promoter was reversed. We propose that the transcription initiation rate from promoters with GC-rich discriminators, in contrast to the uspA-promoter, is not limited by the stability of the open complex. The findings are discussed in view of models for both direct and indirect effects of ppGpp/DksA on transcriptional trade-offs.
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| 7. |
- Gummesson, Bertil, 1977, et al.
(författare)
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Increased RNA polymerase availability directs resources towards growth at the expense of maintenance. : RNAP overproduction
- 2009
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Ingår i: The EMBO journal. - : Wiley. - 1460-2075 .- 0261-4189. ; 28:15, s. 2209-2219
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Tidskriftsartikel (refereegranskat)abstract
- Nutritionally induced changes in RNA polymerase availability have been hypothesized to be an evolutionary primeval mechanism for regulation of gene expression and several contrasting models have been proposed to explain how such 'passive' regulation might occur. We demonstrate here that ectopically elevating Escherichia coli RNA polymerase (Esigma(70)) levels causes an increased expression and promoter occupancy of ribosomal genes at the expense of stress-defense genes and amino acid biosynthetic operons. Phenotypically, cells overproducing Esigma(70) favours growth and reproduction at the expense of motility and damage protection; a response reminiscent of cells with no or diminished levels of the alarmone guanosine tetraphosphate (ppGpp). Consistently, we show that cells lacking ppGpp displayed markedly elevated levels of free Esigma(70) compared with wild-type cells and that the repression of ribosomal RNA expression and reduced growth rate of mutants with constitutively elevated levels of ppGpp can be suppressed by overproducing Esigma(70). We conclude that ppGpp modulates the levels of free Esigma(70) and that this is an integral part of the alarmone's means of regulating a trade-off between growth and maintenance.
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| 8. |
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| 9. |
- Hansson, Frida, et al.
(författare)
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Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression
- 2008
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Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. Results: Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. Conclusion: The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts. © 2008 Hansson et al, licensee BioMed Central Ltd.
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| 10. |
- Lundbäck, Bo, et al.
(författare)
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Epidemiology of respiratory symptoms, lung function and important determinants : Report from the Obstructive Lung Disease in Northern Sweden project
- 1994
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Ingår i: Tubercle and Lung Disease. - 0962-8479 .- 1532-219X. ; 75:2, s. 116-126
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Tidskriftsartikel (refereegranskat)abstract
- SETTING: Cross-sectional epidemiological study based on a representative sample of the general population in northern Sweden. OBJECTIVES: To assess the prevalence of respiratory symptoms, the role of respiratory symptoms as indicators of impairment of lung function, and to define risk factors for respiratory symptoms and lung function impairment. DESIGN: The 1340 subjects of 6610 who reported respiratory symptoms suggestive of asthma or chronic bronchitis in a postal questionnaire study were invited to a structured interview and lung function tests. A control group of 315 subjects was also invited. Risk factors were assessed from the postal questionnaire. RESULTS: 400 subjects in the symptomatic group had attacks of breathlessness and wheezing, while none in the control group had them, corresponding to 7% of the original study population. Chronic productive cough was present in 537 subjects, of whom 13 were from the control group, suggesting that 12% of the original study population had this symptom. Persistent wheeze was the symptom that predicted the greatest proportion of cases of impaired lung function. Attacks of breathlessness, wheezing, long-standing cough and sputum production were all related to age, smoking and a family history of asthma. Both chronic productive cough and impaired lung function correlated strongly with smoking and age, and their prevalences differed in different socio-economic groups. CONCLUSION: Impaired lung function can be predicted from respiratory symptoms. Data collected in postal questionnaires suffice for the identification of risk factors. Combinations of symptoms gave greater odds ratios than individual symptoms.
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