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- Ahmed, R K S, et al.
(författare)
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Antigen-specific beta-chemokine production and CD8(+) T-cell noncytotoxic antiviral activity in HIV-2-infected individuals
- 2005
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Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 61:1, s. 63-71
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus-2 (HIV-2) is less pathogenic than HIV-1, and the disease progression in HIV-2-infected individuals seems to be similar to that seen in HIV-1-infected long-term nonprogressors. Cell-mediated immune responses and the production of noncytotoxic CD8(+) T-cell antiviral factors (CAF) and beta-chemokines have been correlated to protection against HIV-1 and associated with asymptomatic infection and slower disease progression. We investigated the antigen-induced beta-chemokine production in HIV-2-infected patients living in Sweden and in Guinea-Bissau. We also compared in vitro CD8(+) T-cell-mediated noncytotoxic antiviral activity against beta-chemokine-sensitive R5 virus (HIV-1(Bal)) and beta-chemokine-insensitive X4 virus (HIV-1(IIIB)) in HIV-2-infected patients with that in HIV-1-infected patients. HIV-2-specific beta-chemokine production was demonstrated in a majority of the HIV-2-infected subjects. CD8(+) T cells of both HIV-1 and HIV-2-infected individuals suppressed R5 virus replication in vitro in a similar manner, while the inhibition of X4 virus replication seemed to be more frequent and of a higher magnitude among HIV-2-infected patients compared to HIV-1-infected subjects. Taken together, our results indicate that the production of CD8(+) T-cell noncytotoxic antiviral factors may contribute to the low transmission of the virus and slower disease progression in HIV-2-infected patients.
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- Andersson, S, et al.
(författare)
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Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses in HIV-2-infected and in HIV-2-exposed but uninfected individuals in Guinea-Bissau
- 2005
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Ingår i: Clinical and Experimental Immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 139:3, s. 483-489
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Tidskriftsartikel (refereegranskat)abstract
- Human immunodeficiency virus (HIV)-2-specific T lymphocyte proliferative responses were determined in cultures of peripheral blood mononuclear cells from HIV-2-exposed uninfected individuals, HIV-2-infected individuals and HIV-negative controls in Guinea-Bissau. Increased HIV-2-specific T lymphocyte proliferative responses were detected in both groups compared to HIV-negative controls (healthy HIV-uninfected individuals without known exposure to an HIV-infected person); five out of 29 of the HIV-2-exposed uninfected and half (16 of 32) of the HIV-2-infected individuals had stimulation indexes >2, compared to one out of 49 of the HIV-negative controls (P = 0.003 and P < 0.0001, respectively). The exposed uninfected individuals had reactivity to a HIV-2 V3-peptide corresponding to amino acids 311-326 of the envelope glycoprotein, while the HIV-2-infected people reacted mainly to HIV-2 whole viral lysate. Thus, this study demonstrates a high degree of HIV-2-specific T helper cell activity, as measured by lymphocyte proliferation, in HIV-2-exposed uninfected individuals as well as in HIV-2-infected subjects. These immune responses could be important for resistance to the infection and for the control of established infection and, thus, play a role in the lower transmission and progression of HIV-2 compared to HIV-1.
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- Biberfeld, G, et al.
(författare)
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Enzyme immunoassays for the demonstration of antibodies to HIV-2SBL-6669 and HTLV-IV (SIVmac).
- 1988
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Ingår i: AIDS. - 0269-9370 .- 1473-5571. ; 2:3, s. 195-9
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Tidskriftsartikel (refereegranskat)abstract
- Enzyme-linked immunosorbent assays (ELISA) were developed for the demonstration of antibodies to HIV-2 using disrupted virions of the SBL-6669 isolate of HIV-2 and the so-called human T-lymphotropic virus type IV (HTLV-IV), recently found to be identical with the simian immunodeficiency virus (SIVmac), as antigens. Three hundred sera from West African subjects, attending an outward clinic in Bissau for examination of suspected tuberculosis, were tested by these two assays as well as by a commercially available anti-HIV-2 ELISA (ELAVIA II). Fifty of these sera were positive in all three ELISAs as well as in Western blot tests against HTLV-IV. Thirty-eight of these positive sera were also tested by an anti-HIV-2 Western blot kit (LAV-Blot II) with positive results. The ELISAs based on SBL-6669 and HTLV-IV antigens had a specificity of 99.6% (one false positive among 250 negative sera) whereas the specificity of ELAVIA II was 94.6% using the recommended cut-off value and 98.4% using a higher cut-off value. Another 58 sera from West African patients, clinically suspected of having AIDS or HIV-related disease, were tested for HIV-2/HTLV-IV antibodies by Western blot and by ELISA against SBL-6669 and HTLV-IV antigens; all of the 30 sera which were positive by Western blot were found to be positive in both ELISAs.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Ekblom, Björn, et al.
(författare)
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Effect of changes in arterial oxygen content on circulation and physical performance.
- 1975
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Ingår i: Journal of applied physiology. - 0021-8987. ; 39:1, s. 71-5
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the effect of different levels of arterial oxygen content on hemodynamic parameters during exercise nine subjects performed submaximal bicycle or treadmill exercise and maximal treadmill exercise under three different experimental conditions: 1) breathing room air (control); 2) breathing 50% oxygen (hyperoxia); 3) after rebreathing a carbon monoxide gas mixture (hypoxia). Maximal oxygen consumption (Vo2 max) was significantly higher in hyperoxia (4.99 1/min) and significantly lower in hypoxia (3.80 1/min) than in the control experiment (4.43 1/min). Physical performance changes in parallel with Vo2 max. Maximal cardiac output (Qmax) was similar in hyperoxia as in control but was significantly lower in hypoxia mainly due to a decreased stroke volume. A correlation was found between Vo2 max and transported oxygen, i.e., Cao2 times Amax, thus suggesting that central circulation is an important limiting factor for human maximal aerobic power. During submaximal work HR was decreased in hyperoxia and increased in hypoxia. Corresponding Q values were unchanged except for a reduction during high submaximal exercise in hyperoxia.
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- Knoop, J., et al.
(författare)
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Improvement in upper leg muscle strength underlies beneficial effects of exercise therapy in knee osteoarthritis: secondary analysis from a randomised controlled trial
- 2015
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Ingår i: Physiotherapy. - : Elsevier BV. - 0031-9406. ; 101:2, s. 171-177
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Although exercise therapy is effective for reducing pain and activity limitations in patients with knee osteoarthritis (OA), the underlying mechanisms are unclear. This study aimed to evaluate if improvements in neuromuscular factors (i.e. upper leg muscle strength and knee proprioception) underlie the beneficial effects of exercise therapy in patients with knee OA. Design Secondary analyses from a randomised controlled trial, with measurements at baseline, 6 weeks, 12 weeks and 38 weeks. Participants One hundred and fifty-nine patients diagnosed with knee OA. Main outcome measures Changes in pain [numeric rating scale (NRS)] and activity limitations [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) physical function subscale and get-up-and-go test] during the study period. Independent variables were changes in upper leg muscle strength and knee joint proprioception (i.e. motion sense) during the study period. Longitudinal regression analyses (generalised estimating equation) were performed to analyse associations between changes in upper leg muscle strength and knee proprioception with changes in pain and activity limitations. Results Improved muscle strength was significantly associated with reductions in NRS pain {B coefficient 2.5 [95% confidence interval (CI) -3.7 to -1.4], meaning that every change of 1 unit of strength was linked to a change of 2.5 units of pain}, WOMAC physical function (-8.8, 95% CI -13.4 to -4.2) and get-up-and-go test (-1.7, 95% CI 2.4 to 1.0). Improved proprioception was not significantly associated with better outcomes of exercise therapy (P > 0.05). Conclusions Upper leg muscle strengthening is one of the mechanisms underlying the beneficial effects of exercise therapy in patients with knee OA. (C) 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.
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- Knoop, J., et al.
(författare)
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Knee joint stabilization therapy in patients with osteoarthritis of the knee: a randomized, controlled trial
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:8, s. 1025-1034
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate whether an exercise program, initially focusing on knee stabilization and subsequently on muscle strength and performance of daily activities is more effective than an exercise program focusing on muscle strength and performance of daily activities only, in reducing activity limitations in patients with knee osteoarthritis (OA) and instability of the knee joint. Design: A single-blind, randomized, controlled trial involving 159 knee OA patients with self-reported and/or biomechanically assessed knee instability, randomly assigned to two treatment groups. Both groups received a supervised exercise program for 12 weeks, consisting of muscle strengthening exercises and training of daily activities, but only in the experimental group specific knee joint stabilization training was provided. Outcome measures included activity limitations (Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC physical function, primary outcome), pain, global perceived effect and knee stability. Results: Both treatment groups demonstrated large (similar to 20-40%) and clinically relevant reductions in activity limitations, pain and knee instability, which were sustained 6 months post-treatment. No differences in effectiveness between experimental and control treatment were found on WOMAC physical function (B (95% confidence interval - CI) = -0.01 (-2.58 to 2.57)) or secondary outcome measures, except for a higher global perceived effect in the experimental group (P = 0.04). Conclusions: Both exercise programs were highly effective in reducing activity limitations and pain and restoring knee stability in knee OA patients with instability of the knee. In knee OA patients suffering from knee instability, specific knee joint stabilization training, in addition to muscle strengthening and functional exercises, does not seem to have any additional value. Dutch Trial Register (NTR) registration number: NTR1475. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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- Makitalo, B, et al.
(författare)
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Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen
- 2004
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 85:Pt 8, s. 2407-2419
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Tidskriftsartikel (refereegranskat)abstract
- The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.
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- Nilsson, C, et al.
(författare)
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Immunization with recombinant modified vaccinia virus Ankara can modify mucosal simian immunodeficiency virus infection and delay disease progression in macaques
- 2002
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 83:Pt 4, s. 807-818
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, the immunogenicity and protective efficacy of a recombinant vaccinia virus-based simian immunodeficiency virus (SIV) vaccine, given alone or in combination with a protein boost, were investigated. Cynomolgus macaques were immunized intramuscularly with modified vaccinia virus Ankara (MVA) expressing the SIVsmenvandgag–polgenes (MVA–SIVsm) at 0 and 3 months (n=4), at 0, 3 and 8 months (n=4) or at 0 and 3 months followed by purified native SIVsm gp148 and recombinant SIVmac p27 in immunostimulatory complexes at 8 months (n=4). One month after the last immunization, the vaccinees, together with four naive control monkeys and four monkeys immunized with wild-type MVA, were challenged intrarectally with 10 MID50SIVsm. At the time of challenge, antibody titres to SIV Env and lymphocyte proliferation responses to whole viral antigen were highest in vaccinees receiving MVA–SIVsm in combination with protein immunizations. Following rectal challenge, one of these vaccinees was completely protected. A prolonged survival time was observed in two of four monkeys in each of the groups immunized with MVA–SIVsm, in two monkeys given MVA–SIVsm followed by protein and in three of four monkeys given wild-type MVA, compared with naive controls. In conclusion, one monkey given the combined vaccine was protected completely against SIVsm infection. Furthermore, immunization with MVA–SIVsm, as well as wild-type MVA alone, seemed to delay disease progression after mucosal SIV infection in a proportion of the monkeys.
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- Pensierosoa, S, et al.
(författare)
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Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children
- 2009
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 106:19, s. 7939-7944
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 infection induces a progressive disruption of the B cell compartment impairing long-term immune responses to routine immunizations. Depletion of specific memory B cell pools occurs during the 1st stages of the infection and cannot be reestablished by antiretroviral treatment. We reasoned that an early control of viral replication through treatment could preserve the normal development of the memory B cell compartment and responses to routine childhood vaccines. Accordingly, we evaluated the effects of different highly-active antiretroviral therapy (HAART) schedules in 70 HIV-1 vertically-infected pediatric subjects by B cell phenotypic analyses, antigen-specific B cell enzyme-linked immunosorbent spot (ELISpot) and ELISA for common vaccination and HIV-1 antigens. Initiation of HAART within the 1st year of life permits the normal development and maintenance of the memory B cell compartment. On the contrary, memory B cells from patients treated later in time are remarkably reduced and their function is compromised regardless of viral control. A cause for concern is that both late-treated HIV-1 controllers and noncontrollers loose protective antibody titers against common vaccination antigens. Timing of HAART initiation is the major factor predicting the longevity of B cell responses in vaccinated HIV-1-infected children.
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- Pinniger, G J, et al.
(författare)
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Tension regulation during lengthening and shortening actions of the human soleus muscle.
- 2000
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Ingår i: European Journal of Applied Physiology. - : Springer Science and Business Media LLC. - 1439-6319 .- 1439-6327 .- 0301-5548. ; 81:5, s. 375-83
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Tidskriftsartikel (refereegranskat)abstract
- In the present study we investigated tension regulation in the human soleus (SOL) muscle during controlled lengthening and shortening actions. Eleven subjects performed plantar flexor efforts on an ankle torque motor through 30 degrees of ankle displacement (75 degrees -105 degrees internal ankle angle) at lengthening and shortening velocities of 5, 15 and 30 degrees. S(-1). To isolate the SOL from the remainder of the triceps surae, the subject's knee was flexed to 60 degrees during all trials. Voluntary plantar flexor efforts were performed under two test conditions: (1) maximal voluntary activation (MVA) of the SOL, and (2) constant submaximal voluntary activation (SVA) of the SOL. SVA trials were performed with direct visual feedback of the SOL electromyogram (EMG) at a level resulting in a torque output of 30% of isometric maximum. Angle-specific (90 degrees ankle angle) torque and EMG of the SOL, medial gastrocnemius (MG) and tibialis anterior (TA) were recorded. In seven subjects from the initial group, the test protocol was repeated under submaximal percutaneous electrical activation (SEA) of SOL (to 30% isometric maximal effort). Lengthening torques were significantly greater than shortening torques in all test conditions. Lengthening torques in MVA and SVA were independent of velocity and remained at the isometric level, whereas SEA torques were greater than isometric torques and increased at higher lengthening velocities. Shortening torques were lower than the isometric level for all conditions. However, whereas SVA and SEA torques decreased at higher velocities of shortening, MVA torques were independent of velocity. These results indicate velocity- and activation-type-specific tension regulation in the human SOL muscle.
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