| 1. |
- Ericsson, Ylva B., et al.
(author)
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Association between thigh muscle strength four years after partial meniscectomy and radiographic features of osteoarthritis 11 years later
- 2019
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In: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 20:1
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Journal article (peer-reviewed)abstract
- Background: Meniscus injury and meniscectomy both entail increased risk of knee osteoarthritis (OA). Thigh muscle weakness is a suggested mediator of OA but there is little evidence of its importance for knee OA development after meniscectomy. This study aimed to examine the association between thigh muscle strength after partial meniscectomy in middle-aged subjects with a non-traumatic meniscal tear and later radiographic knee OA changes. Methods: Thirty-four out of 45 participants in an exercise-trial underwent testing for isokinetic thigh muscle strength 4 years after arthroscopic partial meniscectomy and had radiographic examination 11 years later (15 years post-surgery, mean age at follow-up of 57 years (range 50-61)). Outcomes were grade of joint space narrowing and osteophyte score in the medial tibiofemoral compartment of the operated knee and the contralateral knee. We tested the association between muscle strength at baseline and the radiographic outcomes at follow-up using logistic regression analyses adjusted for sex and overweight. Results: At follow-up, 33/34 subjects had joint space narrowing and 27/34 subjects had osteophytes in the operated knee, in the contralateral knee joint space narrowing was found in 23 subjects. In the operated knee baseline knee extensor and flexor strength were negatively associated with grade of joint space narrowing at follow-up (OR 0.972 and 0.956, p = 0.028 and 0.026, respectively) and also with osteophyte score (OR 0.968 and 0.931, p = 0.017 and 0.011, respectively). In the contralateral knee longitudinal associations between strength and radiographic OA features were similar, OR 0.949-0.972, p < 0.05. Conclusion: The finding that stronger thigh muscles 4 years after meniscectomy were associated with less severe osteoarthritic changes in the medial tibiofemoral compartment of both the operated and contralateral knee 11 years later, may suggest that strong thigh muscles can help to preserve joint integrity in middle-aged subjects at risk of knee OA.
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| 3. |
- Ohlin, Mats, et al.
(author)
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Light chain shuffling of a high affinity antibody results in a drift in epitope recognition
- 1996
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In: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 33:1, s. 47-56
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Journal article (peer-reviewed)abstract
- Human polyclonal and monoclonal antibodies against pathogens and toxins are potentially useful in the treatment of various diseases. A number of human monoclonal antibodies with protective capacity in vitro have been established by conventional hybridoma technology. However, with the development of phage-display technology, the possibility of specifically tailoring antigen-binding properties has improved substantially. We show here that the reactivity of a high affinity, virus-neutralizing human antibody against the AD-2 epitope of cytomegalovirus gB can be modified by introducing other Vkappa sequences together with the original VH sequence. The fine specificity, as determined by the requirement of particular amino acid residues in the epitope, is shifted in these new antibody fragments. It was also evident that the VH/Vkappa pairing was not promiscuous, since antibody fragments selected by phage display retained light chain sequences very similar to the original hybridoma-derived light chain, proving that a high affinity interaction was very dependent on a co-operativity between both variable domains. These findings show that phage display technology might modify the binding properties of pre-existing, high affinity antibodies.
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| 4. |
- Ohlin, Mats, et al.
(author)
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Restricted variable region gene usage and possible rheumatoid factor relationship among human monoclonal antibodies specific for the AD-1 epitope on cytomegalovirus glycoprotein B
- 1994
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In: Molecular Immunology. - : Elsevier BV. - 1872-9142 .- 0161-5890. ; 31:13, s. 983-991
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Journal article (peer-reviewed)abstract
- The nucleotide sequences of the variable region genes encoding five different human, high affinity antibodies, specific for the major neutralization determinant (AD-1) expressed by human cytomegalovirus glycoprotein B (gp58/116), have been determined. Three of the five heavy chain variable regions belonged to the small VHV-family, although they combined with a diverse set of light chains (V kappa IIIb, V lambda II and V lambda III). The other two antibodies belonged to VH-families III and IV. One of the VHV-family genes most likely originated from a previously unreported germline gene or allele, since it carries a nine nucleotide insert in framework 1. In addition, V lambda-genes showed variable homology (77-95%) to known germline sequences, while V kappa-genes showed high homology (approximately 98%) with their proposed germline origin. Despite the close homology of the V kappa IIIb-gene used to express one of the antibodies with its corresponding germline gene, the protein did not strongly express some idiotypes associated with this light chain family. There is, thus, no direct relation between the expression of these crossreactive idiotypes and the use of even modestly mutated light chains belonging to this V kappa-family, which has been implicated in the development of anti-idiotypic networks possibly inducing autoantibodies, such as rheumatoid factors.
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| 6. |
- Owman, Henrik, et al.
(author)
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Association between findings on delayed gadolinium-enhanced magnetic resonance imaging of cartilage and future knee osteoarthritis.
- 2008
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In: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 58:6, s. 1727-1730
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the predictive value of the delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) index with regard to future radiographic osteoarthritis (OA). METHODS: In 1998, 17 knees in 11 men and 4 women with knee pain, normal results of weight-bearing radiography, and arthroscopic cartilage changes ranging from superficial fibrillation to fissuring and softening were examined using dGEMRIC. Six years later, 16 of the 17 knees were reassessed for radiographic OA changes. RESULTS: At followup, 9 of the 16 knees showed radiographic OA changes. Two of them had undergone a knee joint replacement due to OA. In the knees with radiographic OA, the dGEMRIC index at baseline was lower than that in the knees without radiographic OA (P = 0.03). CONCLUSION: The results of the present study support the dGEMRIC index as a clinically relevant measure of cartilage integrity and suggest that a low index may be predictive of the development of knee OA.
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| 7. |
- Owman, Henrik
(author)
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Human studies evaluating dGEMRIC as a prognostic tool for knee osteoarthritis
- 2014
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Doctoral thesis (other academic/artistic)abstract
- Osteoarthritis (OA) is the most common joint disorder worldwide, causing joint pain and stiffness. The current gold standard for diagnosing knee OA is radiography. However, the disease has often progressed well beyond the point of no return once radiographic cartilage changes become visible. Identifying changes in cartilage at an early stage of OA would allow curative or prophylactic treatment to be instigated much earlier than today. Early in the progression of the disease, the articular cartilage is depleted of glycosaminoglycans (GAGs), which are responsible for cartilage load distribution and compressive stiffness. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage, abbreviated dGEMRIC, can be used to estimate the GAG content of cartilage. A contrast medium is used, the concentration of which in the cartilage is inversely proportional to the amount of GAG. The purpose of this work was to evaluate dGEMRIC as a prognostic tool for knee cartilage changes and knee OA in humans. It was found that dGEMRIC could be used to predict the development of radiographic knee OA in patients at risk of developing OA. An association was also found between dGEMRIC values and important features of knee OA, such as joint space narrowing and osteophytes (bony changes). Unloading of joints has previously been shown to affect the constituents of cartilage. The knees of patients with ankle fractures, prescribed unloading of the injured leg for six weeks, were investigated. Unloading resulted in a measurable effect on the constituents of the knee cartilage, seen as a decrease in GAG content and an increase in the range of dGEMRIC values. These findings should be taken into account when considering treatment of patients involving an unloading regimen. Anterior cruciate ligament (ACL) injury has previously been shown to be an important risk factor for the development of OA. Patients who had sustained an ACL injury 20 years earlier, who had not undergone ACL reconstruction, were investigated. Notably, these patients showed good cartilage quality and subjective knee function, similar to that in healthy reference groups. This is an important finding and should be considered when recommending treatment for patients with ACL injuries.
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