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Biomedical subjects

Mats Grönblad

Publications and source records attributed to Mats Grönblad.

6 recordsLinked to original sources

Complement membrane attack complexes in pathologic disc tissues.

STUDY DESIGN: Complement membrane attack complexes were located in lumbar spine disc tissues by immunohistochemistry. Their occurrence was compared in control discs obtained from organ donors (CD), discs showing a normal macroscopic anatomy, samples of intervertebral disc herniations (DH), and intervertebral discs found to be degenerated by discography, but not herniated (DD). OBJECTIVE: To look for a possible role of complement activation, specifically complement membrane attack complexes, an end product of the classic immune complex-mediated complement activation pathway, in disc pathophysiology. SUMMARY OF BACKGROUND DATA: Recent immunohistochemical and biochemical studies suggest a possible role for immune complexes, as observed by immunohistochemical location and biochemical assay of immunoglobulins M and G in intervertebral disc pathophysiology. Immune complexes may trigger complement activation and ultimately cell lysis. There are, however, currently no reports on complement activation in disc tissues, although immune (antigen-antibody) complexes have been demonstrated. Such immune complexes have been reported to occur on or near to disc cells in DH tissues. METHODS: Thin frozen sections of disc tissue from CD (n = 9 discs), DH (n = 58 discs), and DD (n = 11 discs) were cut and then immunostained with a monoclonal antibody to the complement membrane attack complex (C5b-9) using avidin-biotin complex (ABC) immunostaining. The presence or absence of complement membrane attack complex immunoreactivity was compared in the various subtypes of DH and also with preoperative duration of radicular pain. RESULTS: Complement membrane attack complexes could be observed in none of the CDs studied. In contrast, in more than one third of both the DH (21/58, 36.2%) and the DD (4/11, 36.4%), immunoreactivity to complement membrane attack complexes could be observed in disc cells. In DD discs, immunoreactivity to complement membrane attack complexes was most often present in anulus fibrosus samples (5/13, 38.5%). With respect to subtype of DH, complement membrane attack complexes were observed in 19 of 36 sequestrated discs (52.8%), 1 of 16 extrusions (6.3%), and 1 of 6 protrusions (16.7%). Complement membrane attack complexes were more often present with shorter pain duration (P= 0.03), but showed no relation to age. Disc cells often showed a heavy staining pattern for complement membrane attack complexes, suggesting an abundance of these complexes lodged in the membrane of the cells. CONCLUSIONS: The predominant presence of complement membrane attack complexes in sequestrated disc tissue could suggest a role in DH tissue-induced sciatica. Possibly immune (antigen-antibody) complexes, reported in previous studies, trigger the classic pathway of complement activation, with complement membrane attack complexes as the final product. Complement membrane attack complexes also appear to have some as yet undefined role in degenerated nonherniated disc tissue, with a predominant presence in the anulus fibrosus cells of such discs.

Adult↗

The diagnostic value of contrast-enhanced magnetic resonance imaging in the detection of experimentally induced anular tears in sheep.

STUDY DESIGN: An investigation of the visualization of experimental anular tears using contrast-enhanced magnetic resonance imaging. OBJECTIVES: To investigate how different kinds of experimentally induced anular tears can be visualized on contrast-enhanced magnetic resonance imaging. SUMMARY OF BACKGROUND DATA: Because the outer part of the anulus is innervated, tears of this part of disc are considered one cause for lumbar back pain. Moreover, clinical and experimental studies suggest that anular injuries may lead to a progressive degeneration of the entire disc. In the human disc, vascularized anular tears associated with disc degeneration can be visualized with contrast-enhanced magnetic resonance imaging, but acute peripheral anular injuries, probably caused by sudden trauma, have not been studied with this method. METHODS: Two adjacent lumbar discs in adult sheep (n = 11) were injured with a scalpel blade. The L2-L3 discs were injured superficially, whereas in the L3-L4 discs, the incision reached the nucleus pulposus (full-thickness injury). In seven animals, only a stab incision was made to the disc, and in four animals, a small fragment (5 x 2 x 3 mm) of anulus was cut and removed. The animals were killed 3 weeks (acute injury, n = 5) and 3 months (subacute injury, n = 6) after surgery. Five minutes before death, gadolinium-diethylenetriaminepentaacetic acid was injected intravenously. After death, the whole lumbar spines were excised and 1.5-T high-field magnetic resonance imaging was immediately performed. Thereafter, the disc samples were examined histologically to determine the existence of blood capillaries. RESULTS: In all injured discs, the injured area was macroscopically visible. Histologically, blood capillaries, lamellar destruction, and granulation tissue were clearly seen in every injured anulus. Contrast-enhanced magnetic resonance imaging showed that the superficial injuries were only occasionally visible in magnetic resonance imaging (3 of 11), whereas the full-thickness injuries were visible in a majority of the discs (8 of 11). In magnetic resonance imaging, the size of the injury did not relate to the enhancement intensity. The subacute injuries, particularly the full-thickness injuries, were more often visualized than the acute ones. CONCLUSION: Even though macroscopically visible and histologically evident, it was not always possible to demonstrate experimental anulus injuries by contrast-enhanced magnetic resonance imaging. This experimental study shows that further research work is needed to develop more sensitive methods to detect peripheral, relatively small, but probably clinically important disc injuries.

Animals↗

Oncoprotein c-Fos and c-Jun immunopositive cells and cell clusters in herniated intervertebral disc tissue.

The oncoproteins c-Fos and c-Jun create a transcriptional site early response activating protein (AP-1) mediating the regulation of gene expression in response to extracellular signalling by, for example, cytokines. These proteins are important in the signalling pathway from the cell membrane to the nucleus. Previously, oncoproteins have been located in articular synovium and in chondrocytes, participating in transcription. There is, however, no such study of intervertebral disc tissue. In disc degeneration and after herniation, cell proliferation markers have been demonstrated. In the present study we visualize the AP-1 transcriptional site factors c-Fos and c-Jun in 38 human herniated intervertebral disc tissue samples by immunohistochemical staining with monoclonal antibodies. No immunoreactivity could be observed in control disc tissue, indicating that after herniation, disc cells are entering from the resting stage to the cell cycle. Furthermore, c-Jun immunoreactivity was also observed in disc cell clusters, thus demonstrating them to be active transcriptional sites in disc tissue. c-Fos immunoreactivity was seen in 15/38 and c-Jun in 28/38 herniated discs (39% and 74% respectively). Immunopositive groups of disc cells were noted in 7/28 (25%) of the oncoprotein-immunopositive samples. We did not see any difference in immunoreactivity between female and male patients. Furthermore, we did not notice any statistical difference regarding the immunoreaction for proto-oncogenes c-Fos and c-Jun in extrusions, sequesters and protrusions. Nor did immunostaining show any significant relationship with preoperative pain duration. We concluded that, in herniated disc tissue, the oncoproteins c-Fos and c-Jun are activated in disc cells and cell clusters. In the future, learning more about this transcriptional signal pathway may result in new specific treatments for intervertebral disc pathology.

Acute Disease↗

Blood clots in vessels surrounding symptomatic nerve roots in disc herniation patients: a pilot study.

Mechanical compression and biochemical influences, e.g. by various inflammatory cells and mediators, have been suggested to be involved in the pathophysiology of sciatica. In addition, it has been suggested, but so far not clearly demonstrated, that blood pooling in the venous blood vessels surrounding nerve roots may contribute to impaired nerve root function and sciatica. There is also more direct evidence from studies on an animal model that nucleus pulposus (NP) tissue may induce blood vessel thrombosis. In the present study, a specific monoclonal antibody to platelet membrane glycoprotein complex GPIIb-IIIa was used for direct visualization of blood clots in tissue samples removed from the vicinity of symptomatic nerve roots in 20 disc herniation (DH) patients. For 12 patients, the DH was primary, for 7 patients recurrent and for 1 patient the index operation was for root canal stenosis following a DH operation 3 months earlier. Blood clots immunoreactive to GPIIb-IIIa were observed in small blood vessels in 11/20 tissue samples (55%), in 5/12 patients (42%) with primary DH and in 5/7 patients (71%) with recurrent DH. The presence or absence of GPIIb-IIIa complex immunoreactivity did not show a statistically significant relationship with pain duration, DH type (primary or recurrent), gender or straight leg raising (SLR). Thus, though immunohistochemically demonstrable, the observed periradicular blood clots could not be established to have a clinical role in sciatica in this pilot study.

Adolescent↗

Efficacy of cold gel for soft tissue injuries: a prospective randomized double-blinded trial.

BACKGROUND: The use of cold treatment to limit edema, decrease pain, and induce effective muscle relaxation in soft tissue injuries is widespread. PURPOSE: To compare the efficacy of a novel cold gel with that of a placebo gel in patients with a soft tissue injury. STUDY DESIGN: Prospective randomized double-blinded controlled study. METHODS: Seventy-four patients with sports-related soft tissue injury were randomly assigned to active cold gel (Ice Power) or placebo gel groups. The gel was applied four times daily on the skin for 14 days. Clinical assessment was made after 7, 14, and 28 days with use of visual analog scale ratings. RESULTS: Pain scores decreased from 59 to 30 during the first week, to 14 by the second, and to 7 by the end of study in the cold gel group. In the placebo group, pain scores decreased from 58 to 45, 26, and 13, respectively (significant difference). Patient satisfaction with treatment was 71 in the cold gel group and 44 in the placebo group (significant difference). Disability decreased significantly more rapidly in the cold gel group. CONCLUSIONS: Cold gel therapy provided an effective and safe treatment for sports-related soft tissue injuries.

Adult↗