Gene/Protein Disease Symptom Drug Enzyme Compound
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Although the management of the PCL-injured knee remains controversial, there is a group of patients who will develop accelerated traumatic arthritis in whom surgical intervention is warranted. PCL reconstruction with a patellar tendon graft can reliably restore objective stability in over 90% of patients. Strict attention to detail, however, especially with respect to tunnel placement, is necessary to insure success.
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PMID:Posterior cruciate ligament reconstruction with patellar tendon autograft. 795 83

PCL reconstruction is often a necessary procedure to regain functional knee stability. The procedures used are not able to precisely recreate normal anatomy but are able to provide functional stability to posteriorly destabilized knees when properly performed. Our arthroscopic-assisted procedure limits the soft tissue dissection required and enables the best possible visualization for accurate graft placement. This limits scarring and maximizes the ability of the surgeon to provide posterior knee stability. Allograft tissue, when used as an ACL substitute, was initially believed to be as good as autogenous tissue. It is now believed to be inferior because of slower healing and a tendency to attenuate. PCL allograft reconstructions have not been adequately studied to determine if this same tendency of graft attenuation occurs. In many knees, however, adequate autogenous tissue may not be available, and the only chance to regain stability requires using an allograft. It is in these circumstances that the authors recommend allograft reconstructions.
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PMID:Reconstruction of the posterior cruciate ligament with allograft. 795 85

In conclusion, PCL injuries occur more commonly than previously noted. The PCL-deficient knee is a serious pathology; it is one of functional disability, not functional instability as seen with an ACL disruption. This functional disability is secondary to pain and inflammation from articular cartilage degeneration. The degeneration process occurs over a period of time normally greater than 5 years; eventually knee function is seriously limited. The rehabilitation of the PCL reconstructive or nonoperative patient is greatly dependent on dynamic quadriceps stability. The biomechanics of the PCL and PLC during various exercises are not well understood; however, research is being performed to advance the clinical management following these injuries. The clinician must realize that tremendous tibiofemoral shear forces are created during various knee exercises, in both the closed and open chain. In particular, various knee exercises, in both the closed and open chain. In particular, there are tremendous stresses applied to the PCL during OKC-resisted knee flexion. The clinician must also realize the role of the hamstrings during most closed chain exercises; therefore the author recommends an early program emphasizing isolated open chain quadriceps strengthening progressing to closed chain drills once adequate quadriceps strength has been established. The numerous clinical challenges for the rehabilitation team to hurdle when treating a PCL-injured knee patient have been discussed in this article. The PCL rehabilitation program can no longer be thought of an an ACL rehabilitation program "turned around." The anatomy, biomechanics, and natural history of the PCL-deficient knee differs dramatically from the ACL-deficient knee, and the treatment approach should reflect these considerations.
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PMID:Rehabilitation of isolated and combined posterior cruciate ligament injuries. 795 89

The phenylacetic acid transport system (PATS) of Pseudomonas putida U was studied after this bacterium was cultured in a chemically defined medium containing phenylacetic acid (PA) as the sole carbon source. Kinetic measurement was carried out, in vivo, at 30 degrees C in 50 mM phosphate buffer (pH 7.0). Under these conditions, the uptake rate was linear for at least 3 min and the value of Km was 13 microM. The PATS is an active transport system that is strongly inhibited by 2,4-dinitrophenol, 4-nitrophenol (100%), KCN (97%), 2-nitrophenol (90%), or NaN3 (80%) added at a 1 mM final concentration (each). Glucose or D-lactate (10 mM each) increases the PATS in starved cells (140%), whereas arsenate (20 mM), NaF, or N,N'-dicyclohexylcarbodiimide (1 mM) did not cause any effect. Furthermore, the PATS is insensitive to osmotic shock. These data strongly suggest that the energy for the PATS is derived only from an electron transport system which causes an energy-rich membrane state. The thiol-containing compounds mercaptoethanol, glutathione, and dithiothreitol have no significant effect on the PATS, whereas thiol-modifying reagents such as N-ethylmaleimide and iodoacetate strongly inhibit uptake (100 and 93%, respectively). Molecular analogs of PA with a substitution (i) on the ring or (ii) on the acetyl moiety or those containing (iii) a different ring but keeping the acetyl moiety constant inhibit uptake to different extents. None of the compounds tested significantly increase the PA uptake rate except adipic acid, which greatly stimulates it (163%). The PATS is induced by PA and also, gratuitously, by some phenyl derivatives containing an even number of carbon atoms on the aliphatic moiety (4-phenyl-butyric, 6-phenylhexanoic, and 8-phenyloctanoic acids). However, similar compounds with an odd number of carbon atoms (benzoic, 3-phenylpropionic, 5-phenylvaleric, 7-phenylheptanoic, and 9-phenylnonanoic acids) as well as many other PA derivatives do not induce the system, suggesting that the true inducer molecule is phenylacetyl-coenzyme A (PA-CoA). Furthermore, after P. putida U is cultured in the same medium containing other carbon sources (glucose or octanoic, benzoic, or 4-hydroxyphenylacetic acid) in the place of PA, the PATS and PA-CoA are not detected; neither the PATS nor PA-CoA is found in cases in which mutants (PA- and PCL-) lacking the enzyme which catalyzed the initial step of the PA degradation (phenylacetyl-CoA ligase) are used. PA-CoA has been extracted from bacteria and identified as a true PA catabolite by high-performance liquid chromatography and also enzymatically with pure acyl-CoA:6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum.
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PMID:Aerobic catabolism of phenylacetic acid in Pseudomonas putida U: biochemical characterization of a specific phenylacetic acid transport system and formal demonstration that phenylacetyl-coenzyme A is a catabolic intermediate. 800 92

In reconstructing the ACL, ideal tibial tunnel placement requires an understanding of the unique anatomy of the ACL tibial footprint and its relationship to the PCL, lateral meniscus, and medial tibial part of the spine. In addition to precise placement of the tibial tunnel, its length and angulation are factors to consider. Using consistent anatomic landmarks with attention to detail, the tibial tunnel can be reproducibly placed in a manner that is not detrimental to the graft.
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PMID:Tibial tunnel placement in ACL reconstruction. 800 37

Surgical reconstruction of the PCL has not yet gained the acceptance that ACL reconstruction has achieved. However, in selecting an autograft to restore PCL function in symptomatic posterior knee instability, the free patellar tendon autograft is commonly used at present. Knowledge of the basics in graft healing and of factors regulating this healing process are still limited. It is of interest to determine the biologic response and final morphology of a patellar tendon autograft after PCL replacement. Based on morphological studies in PCL replacement in a sheep model the patellar tendon autograft under-goes necrosis and degeneration followed by a gradual healing process comprising revitalization (i.e. revascularization and cellular proliferation), formation of extracellular matrix components and remodeling. The autograft bone pegs become osseointegrated by 6 weeks. After 2 years, the autograft tissue differs structurally from a ligament, suggesting that the autograft may never approach normal ligament characteristics. Degenerative alterations in the core region of the autograft, the widespread presence of type III collagen and fibronectin, as well as the predominance of thin collagen fibrils do not favor a ligamentization process. The understanding of the autograft healing process remains the prerequisite for a realistic assessment of the biologic PCL replacement and will be a baseline of studies with the goal of influencing the healing process and thus improving the clinical results.
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PMID:The patellar tendon graft for PCL reconstruction. Morphological aspects in a sheep model. 805 42

Restriction of knee motion after total knee replacement was noted to be associated with lengthening of the posterior cruciate ligament during flexion of the knee which was replaced with a cruciate retaining knee prosthesis. The purpose of this study was to measure the excursion length of the PCL in the normal knee in four different cruciate-retaining knee prostheses, and in five cadaveric knees which were replaced with the Tricon prosthesis. For every knee, the tibial part was fixed on a stand and the femoral part was allowed to do flexion-extension motion upon the tibial plateau. The angle of the motion was monitored by the self-readout goniometer. A thin wire cord was attached to the proposed origin site of the PCL on the femur. The wire cord was passed through a tiny hook which was attached to the proposed insertion site of the PCL on the tibia and connected to a dial gauge. The excursion length of the PCL during 90 degrees flexion was measured. The same measurement was repeated five times in each cadaver knee and prosthetic knee studied, and in five knee specimens which were replaced with the Tricon prosthesis. The excursion length of the PCL during 0 degrees to 90 degrees of flexion in five cadaver knees averaged 0.08cm of lengthening. Three different origin sites of the ligament were designated to represent the anterior, middle and posterior part of the ligament.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The excursion length of posterior cruciate ligament during range of motion in prosthetic knee. 806 46

Despite the recent advances in knowledge of the molecular mechanism by which interleukin-4 (IL-4) induces IgE production, little is known about the signal transduction pathway that leads to this event. This study investigated the signal transduction mechanism responsible for IL-4-induced expression of germ-line C epsilon transcripts with use of a human Burkitt lymphoma B-cell line, DND39, which is known to express germ-line C epsilon transcripts in response to IL-4. On stimulation with IL-4, the generation of inositol triphosphate was observed in the cells. In addition, this generation was associated with activation of phospholipase C-gamma 1 (PLC-gamma 1). Although herbimycin A, a potent inhibitor of tryosine kinase, inhibited IL-4-induced activation of PLC-gamma 1 and generation of inositol triphosphate, direct phosphorylation of PCL-gamma 1 was not determined. Nevertheless, IL-4 stimulation could induce activation of FYN but not LYN kinase, suggesting that additional molecule(s) might link FYN kinase to PLC-gamma 1. Interestingly, herbimycin A almost completely inhibited IL-4-induced expression of germ-line C epsilon transcripts when present during the entire culture period. These results indicate that the induction of germ-line C epsilon transcripts in IL-4-stimulated DND39 cells is essentially dependent on the activation of tyrosine kinase, possibly FYN kinase.
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PMID:Possible role of tyrosine kinase activity in interleukin 4-induced expression of germ-line C epsilon transcripts in a human Burkitt lymphoma B-cell line, DND39. 808 70

Ligamentous knee injuries are nowadays more often seen in the office of the family physician, mainly because of an increase in recreational sports injuries. With the help of a questionnaire one can obtain a reliable impression of the injury pattern. The clinical examination is performed in a standardized way, so even in acute ligamentous injuries a correct diagnosis can be obtained at the first examination. The diagnosis of an instability is made with an accurate clinical examination; in case of marginal cooperation of the patient the examination is performed under anesthesia. Depending on the findings, the definitive operation will follow at the same time. In case of a big hemarthrosis we recommend an a.-p. and a lateral X-ray of the knee joint for exclusion of a bony injury before proceeding with the clinical examination. An arthroscopy is indicated in effusions of unclear origin, in the suspicion of meniscal or cartilaginous damage, in a stable knee with hemarthrosis and before definitive stabilization of complex injuries to exclude further damage to other intraarticular structures. Acute ACL ruptures are only operated on in case of bony avulsion fractures, in persons very active in sport and in case of relevant concomitant injuries. Medical collateral injuries without an ACL rupture are usually treated conservatively, except if there is an additional peripheral tear of the meniscus. PCL injuries are seldom operated, except if there is a complex concomitant instability. We aim for an early reconstruction within two weeks after the accident.
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PMID:[Complex internal knee lesions--diagnosis, indications and timing]. 821 48

Nerve regeneration using artificial biodegradable conduits is of increasing interest. The aim of this study is to evaluate the regeneration and maturation of a nerve after long-term implantation (2 years) of a biodegradable poly-L-lactide/poly-epsilon-caprolactone (PLLA/PCL) copolymeric nerve guide in the sciatic nerve of the rat. After harvesting, we evaluated both the regenerated nerves and the controls, using light microscopy, transmission electron microscopy, and morphometric techniques. Remnants of biomaterial were still present after 2 years of implantation, but the foreign body reaction was very mild at this stage, due to the rounded shapes of the polymer debris. Morphometric analysis showed significant differences between the regenerated nerve and the normal sciatic nerve: the number of myelinated fibers is higher, and the mean fiber diameter of the myelinated fibers in the regenerated nerve is smaller. In conclusion, the results demonstrate that the new PLLA/PCL nerve guide can provide optimal conditions for regeneration and maturation of damaged nerves.
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PMID:Long-term evaluation of nerve regeneration in a biodegradable nerve guide. 827 30


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