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Biomedical subjects

R F Warren

Publications and source records attributed to R F Warren.

At least 37 records · Page 2Linked to original sources
PubMed1999

Characterization of chemotactic migration and growth kinetics of canine knee ligament fibroblasts.

Migration and proliferation of ligament fibroblasts are essential for the healing of ligament injuries. This study was designed to evaluate the migration of intraarticular (anterior and posterior cruciate) and extraarticular (medial and lateral collateral) ligament fibroblasts in response to cytokines and to determine the effect of cell passage on cell proliferation. Recombinant human platelet-derived growth factor, hepatocyte growth factor/scatter factor, and bone morphogenic protein-2 stimulated the migration of all ligament cells in a dose-dependent manner, with optimal migration at 10 ng/ml. Recombinant human epithelial growth factor preferentially stimulated the migration of intraarticular ligament fibroblasts, whereas recombinant human interleukin-1 was more effective with extraarticular ligament fibroblasts. Recombinant human insulin-like growth factor-1, insulin-like growth factor-2, transforming growth factor-beta, and fibroblast growth factor had no significant effect on the migration of ligament-derived fibroblasts. These data suggest that specific cytokines stimulate the migration of knee ligament fibroblasts and provide a rationale for possible therapeutic approaches to optimize ligament healing. Fibroblasts derived from the anterior cruciate ligament have been shown to proliferate at a slower rate than those derived from the medial collateral ligament. We have extended these observations and have demonstrated that fibroblasts from both the posterior and anterior cruciate ligaments proliferate at a slower rate than lateral and medial collateral ligament-derived fibroblasts. The differences between the growth rates of intraarticular and extraarticular fibroblasts become insignificant with serial passaging of the cells.

Animals↗
PubMed1999

Differential expression of integrin subunits in canine knee ligament fibroblasts.

A method for measuring the expression of integrin subunits on the cell surface of knee ligament fibroblasts was developed with use of flow cytometry and immunofluorescence. The ligament cells exhibited uniform size and density, as shown by forward and side-scatter properties, and showed minimal nonspecific binding of isotype control antibodies compared with unstained cells. All cells expressed the alpha5 integrin subunit; lateral collateral ligament cells stained with antibody to alpha5 showed a mean fluorescence intensity 2-fold higher than that of medial collateral ligament cells, 1.5-fold higher than that of posterior cruciate ligament cells, and 3-fold higher than that of anterior cruciate ligament cells, indicating a greater expression of the alpha5 subunit by lateral collateral ligament cells than by medial collateral, posterior cruciate, and anterior cruciate ligament cells. All cells expressed the beta1 integrin subunit; the expression by posterior cruciate ligament cells was 3-fold higher than that by medial collateral ligament or lateral collateral ligament cells and 5-fold higher than that by anterior cruciate ligament cells. All cells expressed the beta3 integrin subunit; the expression by posterior cruciate ligament cells was 1.5, 3, and 4.5-fold greater than that by lateral collateral, anterior cruciate, and medial collateral ligament cells, respectively. Our data suggest there is a differential expression of integrin subunits in knee ligament fibroblasts, and this in part may explain differences in their attachment and adherence to extracellular matrix molecules.

Animals↗
PubMed1999

A new Ac-like transposon of Arabidopsis is associated with a deletion of the RPS5 disease resistance gene.

The RPS5 and RFL1 disease resistance genes of Arabidopsis ecotype Col-0 are oriented in tandem and are separated by 1.4 kb. The Ler-0 ecotype contains RFL1, but lacks RPS5. Sequence analysis of the RPS5 deletion region in Ler-0 revealed the presence of an Ac-like transposable element, which we have designated Tag2. Southern hybridization analysis of six Arabidopsis ecotypes revealed 4-11 Tag2-homologous sequences in each, indicating that this element is ubiquitous in Arabidopsis and has been active in recent evolutionary time. The Tag2 insertion adjacent to RFL1 was unique to the Ler-0 ecotype, however, and was not present in two other ecotypes that lack RPS5. DNA sequence from the latter ecotypes lacked a transposon footprint, suggesting that insertion of Tag2 occurred after the initial deletion of RPS5. The deletion breakpoint contained a 192-bp insertion that displayed hallmarks of a nonhomologous DNA end-joining event. We conclude that loss of RPS5 was caused by a double-strand break and subsequent repair, and cannot be attributed to unequal crossing over between resistance gene homologs.

Amino Acid Sequence↗
PubMed1999

Identification of three putative signal transduction genes involved in R gene-specified disease resistance in Arabidopsis.

The RPS5 disease resistance gene of Arabidopsis mediates recognition of Pseudomonas syringae strains that possess the avirulence gene avrPphB. By screening for loss of RPS5-specified resistance, we identified five pbs (avrPphB susceptible) mutants that represent three different genes. Mutations in PBS1 completely blocked RPS5-mediated resistance, but had little to no effect on resistance specified by other disease resistance genes, suggesting that PBS1 facilitates recognition of the avrPphB protein. The pbs2 mutation dramatically reduced resistance mediated by the RPS5 and RPM1 resistance genes, but had no detectable effect on resistance mediated by RPS4 and had an intermediate effect on RPS2-mediated resistance. The pbs2 mutation also had varying effects on resistance mediated by seven different RPP (recognition of Peronospora parasitica) genes. These data indicate that the PBS2 protein functions in a pathway that is important only to a subset of disease-resistance genes. The pbs3 mutation partially suppressed all four P. syringae-resistance genes (RPS5, RPM1, RPS2, and RPS4), and it had weak-to-intermediate effects on the RPP genes. In addition, the pbs3 mutant allowed higher bacterial growth in response to a virulent strain of P. syringae, indicating that the PBS3 gene product functions in a pathway involved in restricting the spread of both virulent and avirulent pathogens. The pbs mutations are recessive and have been mapped to chromosomes I (pbs2) and V (pbs1 and pbs3).

Arabidopsis↗
PubMed1999

Brachial neuritis.

Brachial neuritis is a rare disorder of unknown etiology that causes pain and weakness of the shoulder and upper extremity. There have been many descriptions of the disorder in the literature. The classic symptoms begin with an acute onset of sharp pain in the shoulder girdle. As the pain subsides, weakness occurs. The diagnosis often is difficult to make in the acute setting. Diagnostic tests typically are not helpful, although electromyography may be useful. The treatment is chiefly supportive with analgesics initially followed by range of motion exercises. Full functional recovery is expected in most patients, although the interval may be protracted. Understanding the disorder of brachial neuritis and its course will assist in the diagnosis and treatment.

Brachial Plexus Neuritis↗
PubMed1998

Osteonecrosis of the knee: current clinical concepts.

Osteonecrosis of the knee should be differentiated into two main categories: (1) primary, spontaneous, or idiopathic osteonecrosis and (2) secondary osteonecrosis (e.g., secondary to factors such as steroid therapy, systemic lupus erythematosus, alcoholism, Caisson decompression sickness, Gaucher's disease, hemoglobinopathies, etc.). Spontaneous or primary osteonecrosis of the knee presents with an acute knee pain in elderly patients. It is three times more common in women than in men. Traumatic and vascular theories have been proposed as a causative factor of osteonecrosis of the knee, but the precise etiology still remains speculative. High index of clinical awareness and a good history and physical examination are essential to make an early, accurate diagnosis. Plain radiographs are often normal during the early course of the disease and, in such instances, radioisotope bone scan and magnetic resonance imaging may be helpful. In the early stage of the disease, nonoperative treatment is indicated and many patients, if diagnosed early, have a benign course with a satisfactory pain relief and a good knee function. In patients with advanced stage of the disease, treatment options include arthroscopic debridement, curettage or drilling of the lesion, bone grafting, high tibial osteotomy, use of osteochondral allograft, and unicompartmental or total knee arthroplasty. The choice of treatment should be based on factors such as age of the patient, severity of symptoms, activity level and functional demands on the knee, site and stage of the lesion, and extent of deformity and secondary osteoarthritis. The clinical features and treatment of steroid-induced osteonecrosis of the knee are briefly discussed. In recent years, "postmeniscectomy" osteonecrosis has been reported, but at present its prevalence and pathophysiology remain unknown. It is possible that this may be a preexisting condition that was not recognized at the time of initial consultation or osteonecrosis may develop after meniscectomy in occasional cases.

Adrenal Cortex Hormones↗
PubMed1998

Pretibial cyst formation after anterior cruciate ligament surgery with soft tissue autografts.

Four cases of subcutaneous pretibial ganglion, with direct communication to the tibial tunnel after autologous reconstruction of the anterior cruciate ligament (ACL) with hamstrings or iliotibial band, are reported. Tibial graft fixation was with a staple in three cases, and with a screw and soft tissue washer in one. The average time to ganglion development was 44 months, and all occurred more than 2 years after ACL surgery. At the time of cyst development, no patient had subjective or objective knee instability. No patient had evidence of tibial tunnel enlargement. All ganglion communicated with the tibial tunnel. This communication was shown with magnetic resonance imaging in two cases, which showed the origin at the joint. Three patients elected to have the ganglion removed; in each of these there was a direct communication with the tibial tunnel. Additionally, hardware was removed in all cases, and local autologous bone grafting of the tibial tunnel aperture was done in two. Minimum follow-up after surgical excision was 2 years, without evidence of recurrence.

Adult↗
PubMed1998

A mutation within the leucine-rich repeat domain of the Arabidopsis disease resistance gene RPS5 partially suppresses multiple bacterial and downy mildew resistance genes.

Recognition of pathogens by plants is mediated by several distinct families of functionally variable but structurally related disease resistance (R) genes. The largest family is defined by the presence of a putative nucleotide binding domain and 12 to 21 leucine-rich repeats (LRRs). The function of these LRRs has not been defined, but they are speculated to bind pathogen-derived ligands. We have isolated a mutation in the Arabidopsis RPS5 gene that indicates that the LRR region may interact with other plant proteins. The rps5-1 mutation causes a glutamate-to-lysine substitution in the third LRR and partially compromises the function of several R genes that confer bacterial and downy mildew resistance. The third LRR is relatively well conserved, and we speculate that it may interact with a signal transduction component shared by multiple R gene pathways.

Amino Acid Sequence↗
PubMed1998

Magnetic resonance imaging of the Lisfranc ligament of the foot.

Early recognition of subtle Lisfranc injuries is important, because deformity and disability may develop after initially unremarkable radiographs. The authors studied 23 patients (mean age, 25.4 years) with a history of midfoot trauma with both radiographs and magnetic resonance imaging (MRI). When compared with the uninjured side, diastasis on radiographs ranged from 0 to 2 mm. The MRI revealed 2 intact ligaments, 3 complete tears, and 18 partial tears. All patients with complete tears had at least 2 mm more displacement between the second metatarsal and medial cuneiform, compared with the unaffected side. Because of the presence of complete or near complete rupture, seven patients underwent surgery, and the degree of rupture was confirmed. MRI of five cadaver specimens was also performed, disclosing discrete dorsal and plantar components. MRI was found to be useful in identifying Lisfranc ligament tears. If there is clear diastasis on weightbearing radiographs, MRI is not indicated. Whereas radiographic findings may be equivocal, however, MRI may accurately disclose the degree of ligament disruption.

Adolescent↗
PubMed1998

Effects of exercise on Achilles tendon healing in a rat model.

The effects of motion, or lack of it, on Achilles tendon healing are not well defined. We have recently shown that immobilization has a detrimental effect on tendon healing in a rat model. The aim of this experiment was to determine whether enforced exercise had an additional beneficial effect on the mechanical and functional recovery of divided Achilles tendons in rats. Male Sprague-Dawley rats were randomly allocated into a nonexercise and an exercise group (N = 10 for each group). In both groups the right Achilles tendon was surgically transected. The left, uninjured lower limb served as an internal control. Both groups of animals were housed under identical conditions with the exception that the exercise group swam for 15 minutes per day. Functional performance was determined from the measurement of hindpaw prints of walking rats preoperatively and on alternate postoperative days. On day 15, the animals were killed and weighed, and biomechanical evaluations were performed on both the injured and uninjured Achilles tendon constructs. There were no differences in weight at time of death. All animals had an initial functional deficit that returned to near-normal by day 15. There were significant differences in the morphological and the mechanical properties of the healing Achilles tendon constructs at day 15 when comparing the injured with the uninjured Achilles tendon constructs. Supplemental exercise, however, had no effect on the functional or mechanical recovery of injured or uninjured Achilles tendons in the rat model.

Achilles Tendon↗
PubMed1998

Hamstring and patellar tendon graft response to cyclical loading.

This study evaluates the effect of submaximal cyclical loads on the tendinous portion of the central 10 mm of the patellar tendon compared with doubled semitendinosus and gracilis tendons. Six fresh-frozen cadaveric knee specimens were used for the study. There was no significant difference between the cross-sectional areas of a 10-mm patellar tendon and four strands of hamstring tendon (looped semitendinosus and gracilis) from the same specimen. The mean cross-sectional area was 44.4 mm2 for the patellar tendon and 47.5 mm2 for the four strands of hamstring. The specimens were cyclically loaded for 1000 cycles from 0 to 300 N at a rate of 1 Hz; the materials testing machine was set on load control. There were no significant differences in the strain, stress, or modulus between the 10-mm patellar tendon and four strands of hamstring tendon after 1000 cycles of loading to 300 N. These data substantiate the excellent clinical results obtained with either graft source and support the use of either graft source for ACL reconstruction.

Aged↗
PubMed1998

The skeletally fixed knee hinge for the grossly unstable knee.

This study examined whether a skeletally fixed prefabricated knee hinge can provide the intact or unstable knee with normal motion through a specific arc of motion. Eight cadaveric knee specimens were used. The amount of motion mismatch between knee and hinge motion was evaluated at six different knee flexion angles. With all knee ligaments intact, addition of the hinge resulted in increasing amounts of joint compression with knee flexion. When all knee ligaments were cut, there was some degree of distraction with 0 degrees of knee flexion, which seemed to gradually decrease and become compressive at 80 degrees of flexion. These values were not statistically significant. In contrast, the mismatch between anterior and posterior tibial translation mismatch was statistically significant. With the ligaments intact, the addition of the hinge resulted in increased amounts of posterior tibial translation, which became significant at 80 degrees of flexion. Similarly, when the ligaments were cut with the hinge intact, there was an increasing amount of posterior tibial translation, which became significant at 60 degrees of flexion. There was also a significant amount of anterior tibial translation at 0 degrees in this group. These results indicate that the hinge allows only a limited range of motion that does not significantly alter tibial translation or joint compression or distraction. Whether this amount of motion is enough to improve the outcome of the grossly unstable knee is unknown. The use of a more sophisticated hinge system might accomplish a greater range of anatomic motion before significant mismatch occurs between hinge and knee motion.

Aged↗
PubMed1997

Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder.

The purpose of this study was to test the hypothesis that specific cytokines are involved in the initiation and evolution of the fibrotic process in adhesive capsulitis of the shoulder. After approval from the Institutional Review Board, biopsies of shoulder capsule and synovium were collected during shoulder arthroscopy from 19 patients with adhesive capsulitis, 14 patients with nonspecific synovitis and no fibrosis or clinical evidence of adhesive capsulitis, and seven patients undergoing surgery for another pathology who had a normal capsule and synovium. Immunohistochemical localization with monoclonal antibodies to transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, basic fibroblast growth factor, interleukin-1 beta, tumor necrosis factor-alpha, and hepatocyte growth factor was performed using standard immunoperoxidase techniques. The frequency of cytokine staining was correlated with the clinical diagnosis. Synovial cells, fibroblasts, T-cells, and B-cells were identified with specific antibodies, and newly synthesized matrix was examined for type-I and type-III collagen by immunohistochemical staining. The predominant cell types present were synovial cells and fibroblasts. Staining for type-III collagen in adhesive capsulitis tissues indicated new deposition of collagen in the capsule. There was staining for transforming growth factor-beta and its receptor, platelet-derived growth factor and its receptor, interleukin-1 beta, and tumor necrosis factor-alpha in adhesive capsulitis and nonspecific synovitis tissues, compared with minimal staining in normal capsule. Staining was more frequent in synovial cells than in capsular cells. The frequency of cell and matrix staining for transforming growth factor-beta, platelet-derived growth factor, and hepatocyte growth factor was greater in adhesive capsulitis tissues than in those from patients with nonspecific synovitis. No difference in the frequency of staining between primary (idiopathic) and secondary adhesive capsulitis was found. The results of this study indicate that adhesive capsulitis involves both synovial hyperplasia and capsular fibrosis. Cytokines such as transforming growth factor-beta and platelet-derived growth factor may be involved in the inflammatory and fibrotic processes in adhesive capsulitis. Matrix-bound transforming growth factor-beta may act as a persistent stimulus, resulting in capsular fibrosis. Understanding the basic pathophysiology of adhesive capsulitis is an important step in the development of clinically useful antifibrotic agents that may serve as novel treatments for patients with this conditions.

Adult↗
PubMed1997

Modulation of tendon healing by nitric oxide.

Nitric oxide (NO) is a small, diffusible free radical that is generated from L-arginine by a family of enzymes, collectively termed the nitric oxide synthases. We investigated the role of NO in tendon healing. NO synthase activity and immunoreactivity was absent in un-injured rat Achilles tendon. After surgical division there was a five-fold increase in NO synthase activity and immunoreactivity within the healing tendon at day 7, with a return to near baseline levels at day 14. Inhibition of NO synthase activity with oral administration of N omega-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in cross-sectional area (30% at day 7, p < 0.01, 50% at day 15, p < 0.001) and failure load (24% at day 7, p < 0.01) of the healing Achilles tendon constructs. Rats fed the same regimen of the enantiomer of L-NAME, (D-NAME) had normal tendon healing. These results indicate that nitric oxide synthase is induced during tendon healing and inhibition of nitric oxide synthase inhibits this tendon healing.

Achilles Tendon↗
PubMed1997

Popliteomeniscal fasciculi and the unstable lateral meniscus: clinical correlation and magnetic resonance diagnosis.

We hypothesize that disruption of the fascicular attachments between the popliteus and lateral meniscus can result in gross instability of the meniscus producing locking of the knee. This study brings attention to the importance of the clinical examination, and the need for clinical correlation to magnetic resonance (MR) studies. We report on three patients referred with the history of mechanical locking episodes of their knee. Initial MR examinations were all read as normal before referral to our institution. On close review of these MR examinations, popliteomeniscal fascicular disruption could be seen in each case. Each of these patients had arthroscopic-repair of these meniscal detachments. At 1-year follow-up, all patients had resolution of mechanical symptoms. Each patient had confirmation of their repair with repeat arthroscopy or MR and arthrographic examinations. An anatomic specimen was used to identify the popliteus muscle and tendon, the lateral meniscus, the antero-inferior popliteomeniscal fascicle, and the postero-superior popliteomeniscal fascicle attachments. MR images of the same anatomic specimen show both superior and inferior fasciculus attachments to the capsule. MR examples of the intact and disrupted antero-inferior and postero-superior popliteomeniscal fasciculi have been correlated to anatomic specimens to help familiarize the orthopaedic surgeon with these important stabilizing structures.

Adolescent↗