| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Andersson, P. O., et al.
(författare)
-
Pen injection and change in metabolic control and quality of life in insulin dependent diabetes mellitus
- 1997
-
Ingår i: Diabetes Research and Clinical Practice. - 0168-8227 .- 1872-8227. ; 36:3, s. 169-172
-
Tidskriftsartikel (refereegranskat)abstract
- A second follow-up of metabolic control and quality of life in insulin dependent diabetes mellitus (IDDM) patients who had switched 3 years before from syringe to multiple pen injection treatment, was carried out. A total of 73 consecutive outpatients were enrolled in the initial follow-up study in 1988, 1 year after their changeover to insulin pen, with their metabolic control and quality of life examined. The present study concerns the reexamination of 65 of them in 1990. Their HbA(1c) level was recorded yearly, already from 1987, on. After an enhancement of metabolic control in 1988, exhibited primarily by patients with fewer syringe injections before pen treatment, control up to 1990 was found to have regressed to about baseline level or to have gradually declined. Patients who perceived their ability to self-test blood glucose to have decreased exhibited the least satisfactory course of metabolic control. This is seen to indicate that maintaining self-testing in multiple injection insulin treatment is a very real challenge to this regimen.
|
|
| 5. |
- Bengnér, Malin, et al.
(författare)
-
Independent skewing of the T cell and NK cell compartments associated with cytomegalovirus infection suggests division of labor between innate and adaptive immunity.
- 2014
-
Ingår i: Age (Omaha). - : Springer Science and Business Media LLC. - 0161-9152 .- 1574-4647. ; 36:2, s. 571-582
-
Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) infection induces profound changes in different subsets of the cellular immune system. We have previously identified an immune risk profile (IRP) where CMV-associated changes in the T cell compartment, defined as a CD4/CD8 ratio < 1, are associated with increased mortality in elderly people. Since natural killer (NK) cells have an important role in the defense against viral infections, we examined whether the expansion of CD8 + T cells seen in individuals with CD4/CD8 ratio < 1 is coupled to a parallel skewing of the NK cell compartment. A number of 151 subjects were examined with CMV serology and a flow cytometry panel for assessment of T cell and NK cell subsets. CMV-seropositive individuals had higher frequencies of CD57 + and NKG2C + NK cells and lower frequencies of NKG2A + NK cells, in line with a more differentiated NK cell compartment. Intriguingly, however, there was no correlation between CD4/CD8 ratio and NK cell repertoires among CMV-seropositive donors, despite the profound skewing of the T cell compartment in the group with CD4/CD8 ratio < 1. Conversely, donors with profound expansion of NK cells, defined as NKG2C + NK cells with high expression of CD57 and ILT-2, did not display more common changes in their T cell repertoire, suggesting that NK cell expansion is independent of the T cell-defined IRP. Altogether, these results indicate that the effect of CMV on CD8 T cells and NK cells is largely nonoverlapping and independent.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Fülöp, Tamas, et al.
(författare)
-
Immunosupportive therapies in aging
- 2007
-
Ingår i: Clinical Interventions in Aging. - 1176-9092. ; 2:1, s. 33-54
-
Tidskriftsartikel (refereegranskat)
|
|
| 12. |
- Gibson, Kate L, et al.
(författare)
-
B-cell diversity decreases in old age and is correlated with poor health status
- 2009
-
Ingår i: AGING CELL. - : Wiley. - 1474-9718 .- 1474-9726. ; 8:1, s. 18-25
-
Tidskriftsartikel (refereegranskat)abstract
- Older people suffer from a decline in immune system, which affects their ability to respond to infections and to raise efficient responses to vaccines. Effective and specific antibodies in responses from older individuals are decreased in favour of non-specific antibody production. We investigated the B-cell repertoire in DNA samples from peripheral blood of individuals aged 86-94 years, and a control group aged 19-54 years, using spectratype analysis of the IGHV complementarity determining region (CDR)3. We found that a proportion of older individuals had a dramatic collapse in their B-cell repertoire diversity. Sequencing of polymerase chain reaction products from a selection of samples indicated that this loss of diversity was characterized by clonal expansions of B cells in vivo. Statistical analysis of the spectratypes enabled objective comparisons and showed that loss of diversity correlated very strongly with the general health status of the individuals; a distorted spectratype can be used to predict frailty. Correlations with survival and vitamin B12 status were also seen. We conclude that B-cell diversity can decrease dramatically with age and may have important implications for the immune health of older people. B-cell immune frailty is also a marker of general frailty.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Jonasson, Lena, et al.
(författare)
-
Low serum ß-carotene reflects immune activation in patients with coronary artery disease
- 2003
-
Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - 0939-4753 .- 1590-3729. ; 13:3, s. 120-125
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aim: Low serum levels of antioxidant vitamins are associated with coronary artery disease (CAD). An immunomodulatory effect of antioxidants has been proposed. The aim of the study was to investigate whether an increased immune response in CAD patients was associated with suppressed circulating levels of antioxidant vitamins. Methods and Results: Forty-four men with stable angina and angiographically verified CAD were included as well as 69 healthy controls. T cell subsets in peripheral blood were quantified by 3-colour flow cytometry. C-reactive protein (CRP), soluble interleukin-2 receptor (sIL-2R) and the lipophilic antioxidants a-tocopherol, ß-carotene and lycopene were determined in serum. Compared with controls, patients had signs of an enhanced inflammatory activity assessed by significantly increased levels of CRP, sIL-2R and CD4+CD25+T cell subsets. Patients also had significantly lower ß-carotene and lycopene levels whereas a-tocopherol levels did not differ. The increased inflammatory/immune parameters in patients showed a significant inverse relationship to serum ß-carotene but not to lycopene or a-tocopherol. Conclusions: Low serum ß-carotene in CAD patients reflects activation of the immune system. Inflammation should be considered as an important confounding factor when analysing data on ß-carotene and CAD. © 2003, Medikal Press.
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Laytragoon-Lewin, Nongnit, et al.
(författare)
-
Perforin, CD28 and CD95 expression in circulating CD4 and CD8 cells as predictors of head and neck (H&N) cancer patient survival
- 2014
-
Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 31:12, s. 290-
-
Tidskriftsartikel (refereegranskat)abstract
- Long-term survival of H&N cancer patients has not improved significantly over the last 30 years. The possibility of using circulating blood cell phenotypes as a prognostic biomarker of H&N cancer patient was investigated in this study. Pre-treatment, circulating T lymphocyte subpopulations as well as the survival time of the patients in question were studied. Upregulated CD4+ perforin+ and CD8+ CD95+ but downregulated CD4+ CD28+ (p < 0.001) were detected in H&N cancer patients. With 3 years of follow-up time, an increase in the frequency of the pre-treatment, circulating CD4+ perforin+ cells and CD8+ perforin+ cells was showed to have reverse effects on the survival time in H&N cancer patients (p < 0.01). Detection of perforin? frequency in CD4+ and CD8+ lymphocyte by FACS is fast, simple and cost-effective. A potential role of perforin expression in CD4+ and CD8+ cells as a prognostic biomarker for H&N cancer patient in the clinical setting was suggested.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
- Nilsson, Bengt-Olof, et al.
(författare)
-
Morbidity does not influence the T-cell immune risk phenotype in the elderly : Findings in the Swedish NONA Immune Study using sample selection protocols
- 2003
-
Ingår i: Mechanisms of Ageing and Development. - : Elesvier. - 0047-6374 .- 1872-6216. ; 124:4, s. 469-476
-
Tidskriftsartikel (refereegranskat)abstract
- A critical issue in our understanding of ageing and the immune system refers to the health status of the population from which inferences are drawn. The commonly used SENIEUR protocol, selecting individuals representing 'normal ageing' has recently been under debate because a substantial amount of individuals with various health problems are excluded. The aim of the present study was to investigate the influence of morbidity on immune parameters and to evaluate the associations with the T-cell immune risk phenotype (IRP), related to cytomegalovirus (CMV) seropositivity by applying the SENIEUR protocol and the OCTO-Immune protocol in the unselected population based sample (n = 138) of oldest-olds, participating in the Swedish NONA Immune Study. The SENIEUR protocol excluded over 90% of the sample whereas the OCTO-Immune protocol excluded almost 65% of the sample. Three independent groups, very healthy (SENIEUR), moderately healthy (OCTO-Immune) and frail (non-SENIEUR/non-OCTO-Immune) were created. Flow cytometry studies on lymphocyte sub-populations revealed no significant difference in CD4/CD8 ratio, CD3+CD4-CD8+, CD3+CD4+CD8-, CD8+CD57+CD28-, CD8+CD56+CD57- or CD8+CD56+CD57+ between the very healthy, moderately healthy and the frail subsamples. Our findings indicate that morbidity does not significantly influence the T-cell immune risk profile in the elderly, and we suggest the inclusion of broader samples in future immunogerontological studies.
|
|
| 28. |
- Nilsson, Bengt-Olof, 1954-, et al.
(författare)
-
The Immune Risk Phenotype and IL-6 among Nonagenarians and Associations with Morbidity and Mortality : Findings from the Swedish NONA Immune Longitudinal Study
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In this NONA immune longitudinal study, we examine 4-year mortality in relation to a set of laboratory parameters, morbidity and cause of death in a population-based sample of oldest-old individuals (n=138). Four groups were constructed based on levels for the CD4/CD8 ratio (above or below one = IRP, immune risk phenotype group) and levels for IL-6 (below or above the median 3.15 pg/mL). 4-year mortality was higher in the “IRP” group (73 %), the “IL-6” group (64 %), and the “Double risk group” (82 %) compared with the “No risk” group (29 %; p-values between .005 and .000). Cognitive dysfunction and dementia were more common in the two groups with elevated IL-6 levels (p-values between .014 and .001), whereas cardiovascular disease tended (p = .081) to be associated with both “IRP” and “IL-6” groups. The most common cause of death was related to cardio- and cerebrovascular disease (59 %,), followed by infection in 15 % of the cases and cancer in 7 %. Despite their strong associations with 4-year mortality, neither IRP nor IL-6 could be linked to any specific cause of death, possibly because both IRP and IL-6 are multi-factorial risk factors, being associated with several different diseases and mechanisms which cause death.
|
|
| 29. |
- Nilsson, Bengt-Olof, 1954-
(författare)
-
The Immune System in the Oldest-Old : Clinical and Immunological Studies in the NONA Immune Cohort
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The oldest-old (people aged 80 or older) constituted 5 % of the population in Sweden in 2000, an increase from 1.5 % fifty years earlier. The immune system undergoes dramatic changes at high age, sometimes referred to as “immunosenescence”. However, the natures of these changes, and in particular, their clinical consequences are incompletely understood. In a previous longitudinal study, a set of immune parameters were identified and termed immune risk phenotype (IRP) because of an association with increased mortality. The IRP consists of changes in the T lymphocyte compartment, in particular an inverted CD4/CD8 ratio. The IRP was found to be associated with cytomegalovirus (CMV) infection, which through expansions of cytolytic anti-viral CD8 cell responses was ascribed a role in the development of IRP. The general aim of this thesis was to increase the knowledge of changes in the immune system and their clinical consequences in the oldest-old. The population-based random sample of the longitudinal NONA-Immune Study (n = 138, mean age 90 years at baseline) was used for all investigations.In paper I, the effects on sample size of various exclusion protocols for immune studies of the elderly was examined. The commonly used SENIEUR protocol, selecting individuals representing ‘normal ageing’, excluded 90 % of nonagenarians. Based on different protocol criteria, individuals were grouped into ‘very healthy’, ‘moderately healthy’ or ‘frail’. The prevalence of CMV was similar across the groups. Further, differentiated CD8 populations associated with CMV, i.e. those expressing CD56, CD57 and CD45RA while lacking expression of CD27 and CD28, were equally distributed across the groups of the oldest-old, but were, as expected, significantly increased in the elderly compared to a middle aged control group. The findings showed that lymphocyte subsets associated with IRP might serve as significant biomarkers of ageing independent of the overall health status, also supporting the notion that immunological studies of the oldest-old should be done in population-based non-selected populations.The IRP and the presence of low-grade inflammation, for example increase of IL-6 in plasma, constitute major predictors of 2-year mortality in the oldest-old. In paper II, the CD4/CD8 ratio and IL-6 were found to predict 97 % of observed survival and 57 % of deaths over 2 years. The impact of IRP and IL-6 on 2-year survival was independent of age, sex and several diseases. The longitudinal design allowed temporal evaluations, suggesting a sequence of events starting with IRP and leading to inflammation in the decline state. Four-year mortality in the oldest-old (paper III) was found to be mainly related to markers of inflammation and IRP. Individuals with both inverted CD4/CD8 ratio and high IL-6 level had significantly higher 4 year mortality (82 %) compared to individuals with CD4/CD8 ratio ³ 1 and low IL-6 level (29 %) at baseline. The presence of IRP and increased IL-6 level showed some associations with presence of diseases; in particular, IL6 was associated with the presence of cognitive impairment. However, despite being strong predictors of mortality, IRP and IL-6 could not be linked to any specific cause of death, probably due to the multi-factorial nature of these factors. The prevalence of antinuclear antibodies (ANA) in the oldest-old was higher compared to younger controls (paper IV). The difference across age was most pronounced in men, showing low levels at younger age, whereas the prevalence among the oldest-old men reached a similar level as in women. There was no association between the presence of ANA and IRP, CMV status or health status in the oldest-old.
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
|
|
| 35. |
- Pawelec, Graham, et al.
(författare)
-
Cytomegalovirus and human immunosenescence
- 2009
-
Ingår i: Reviews in Medical Virology. - : John Wiley & Sons. - 1052-9276 .- 1099-1654. ; 19:1, s. 47-56
-
Forskningsöversikt (refereegranskat)abstract
- 'Immunosenescence' is all imprecise term used to describe deleterious age-associated changes to immune parameters observed in all mammals studied so far. Primarily anecdotal evidence implies that failing immunity is responsible for the increased incidence and severity of infectious disease in old people. However, there is a serious dearth of accurate hard data concerning the actual cause of death in the elderly and the contribution thereto of the multitude of age-associated alterations measured in the immune system. Cross-sectional studies comparing those currently young With those currently old reveal a large number of differences in the distribution of immune cell types in the blood, and to some extent the functional integrity of those cells. Many of these parameters differ markedly between individuals infected with CMV and uninfected people, regardless of infection with other persistent herpesviruses. The adaptive arm of immunity appears to be more seriously affected than the innate arm, particularly the T lymphocytes. However, cross-sectional studies suffer the disadvantage that like is not being compared with like, because the conditions applied during the entire life course of the currently elderly were different from those applied now to the young. These differences in environment, nutrition, pathology and possibly genetics, rather than merely age, may be expected to influence the parameters studied. Moreover, pathogen exposure of the currently elderly was also different from contemporary exposure, probably including CMV. Some of the problems associated with cross-sectional studies can be overcome by performing longitudinal studies, as pointed out in an earlier analysis of the Baltimore Longitudinal Ageing study looking at lymphocyte numbers. However, longitudinal studies are challenging in humans. L Nonetheless, the pioneering Swedish OCTO/NONA studies of the very elderly which for the first time included a range of immune parameters, have identified a set of immune parameters predicting mortality at 2, 4 and 6 year follow-up; CMV infection makes a material contribution to this so-called immune risk profile (IRP)'. Whether the IRP is informative in younger individuals and the mechanism of the CMV effect is discussed in this review.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Pawelec, Graham, et al.
(författare)
-
Immunorejuvenation in the elderly
- 2006
-
Ingår i: Rejuvenation Research. - 1549-1684. ; 9:1, s. 111-116
-
Tidskriftsartikel (refereegranskat)
|
|
| 39. |
- Pawelec, Graham, et al.
(författare)
-
Is immunosenescence infectious?
- 2004
-
Ingår i: Trends in immunology. - 1471-4906 .- 1471-4981. ; 25:8, s. 406-410
-
Tidskriftsartikel (refereegranskat)
|
|
| 40. |
|
|
| 41. |
- Pawelec, G, et al.
(författare)
-
The SENIEUR protocol after 16 years.
- 2001
-
Ingår i: Mechanisms of Ageing and Development. - 0047-6374 .- 1872-6216. ; 122:2, s. 132-134
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
|
|
| 42. |
- Ross, Owen A., et al.
(författare)
-
Mitochondrial DNA damage in lymphocytes : a role in immunosenescence?
- 2002
-
Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 37:2-3, s. 329-340
-
Tidskriftsartikel (refereegranskat)abstract
- An age-related increase of DNA damage/mutation has been previously reported in human lymphocytes. The high copy number and mutation rate make the mtDNA genome an ideal candidate for assessing damage and to act as a potential biomarker of ageing. In the present study, two assays were developed to evaluate the level of mtDNA4977 and the accumulation of point mutations with age. A competitive polymerase chain reaction (PCR) methodology incorporating three primers was used to detect and quantify the levels of mtDNA4977 and a novel heteroduplex reference strand conformational analysis (RSCA) technique was used to analyse the accumulation of point mutations. The assays were applied to an in vitro model of T cell ageing and ex vivo DNA samples from an elderly cohort of subjects and a younger control group. The mtDNA4977 was detected in all the DNA samples examined but only a very low concentration was observed and no age-related increase or accumulation was observed. No accumulation of point mutations was identified using RSCA within the T cell clones as they were aged or the ex vivo lymphocytes from the elderly cohort. A higher level of variation was observed within the ex vivo DNA samples, verifying the high resolution of RSCA and its ability to identify different mtDNA species, although no correlation with age was observed. The low level of mtDNA damage observed with respect to the ex vivo lymphocyte DNA samples within this study may be due in part to the high turnover of blood cells/mtDNA, which may inhibit the accumulation of genetically abnormal mtDNA that may play a role in immunosenescence. A similar explanation may also apply to the in vitro model of T cell ageing if the vast majority of the cells are replicating rather than entering senescence.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
