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PubMed1991

Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control.

GCN4 encodes a transcriptional activator of amino acid-biosynthetic genes in Saccharomyces cerevisiae that is regulated at the translational level by upstream open reading frames (uORFs) in its mRNA leader. uORF4 (counting from the 5' end) is sufficient to repress GCN4 under nonstarvation conditions; uORF1 is required to overcome the inhibitory effect of uORF4 and stimulate GCN4 translation in amino acid-starved cells. Insertions of sequences with the potential to form secondary structure around uORF4 abolish derepression, indicating that ribosomes reach GCN4 by traversing uORF4 sequences rather than by binding internally to the GCN4 start site. By showing that wild-type regulation occurred even when uORF4 was elongated to overlap GCN4 by 130 nucleotides, we provide strong evidence that those ribosomes which translate GCN4 do so by ignoring the uORF4 AUG start codon. This conclusion is in accord with the fact that translation of a uORF4-lacZ fusion was lower in a derepressed gcd1 mutant than in a nonderepressible gcn2 strain. We also show that increasing the distance between uORF1 and uORF4 to the wild-type spacing that separates uORF1 from GCN4 specifically impaired the ability of uORF1 to derepress GCN4 translation. As expected, this alteration led to increased uORF4-lacZ translation in gcd1 cells. Our results suggest that under starvation conditions, a substantial fraction of ribosomes that translate uORF1 fail to reassemble the factors needed for reinitiation by the time they scan to uORF4, but become competent to reinitiate after scanning the additional sequences to GCN4. Under nonstarvation conditions, ribosomes would recover more rapidly from uORF1 translation, causing them all to reinitiate at uORF4 rather than at GCN4.

Amino Acids↗

PubMed1998

The evolutionarily conserved eukaryotic arginine attenuator peptide regulates the movement of ribosomes that have translated it.

Translation of the upstream open reading frame (uORF) in the 5' leader segment of the Neurospora crassa arg-2 mRNA causes reduced initiation at a downstream start codon when arginine is plentiful. Previous examination of this translational attenuation mechanism using a primer-extension inhibition (toeprint) assay in a homologous N. crassa cell-free translation system showed that arginine causes ribosomes to stall at the uORF termination codon. This stalling apparently regulates translation by preventing trailing scanning ribosomes from reaching the downstream start codon. Here we provide evidence that neither the distance between the uORF stop codon and the downstream initiation codon nor the nature of the stop codon used to terminate translation of the uORF-encoded arginine attenuator peptide (AAP) is important for regulation. Furthermore, translation of the AAP coding region regulates synthesis of the firefly luciferase polypeptide when it is fused directly at the N terminus of that polypeptide. In this case, the elongating ribosome stalls in response to Arg soon after it translates the AAP coding region. Regulation by this eukaryotic leader peptide thus appears to be exerted through a novel mechanism of cis-acting translational control.

Amino Acid Sequence↗

PubMed1999

Mutations in translation initiation factors lead to increased rates of deadenylation and decapping of mRNAs in Saccharomyces cerevisiae.

The turnover of most mRNAs in Saccharomyces cerevisiae begins with deadenylation followed by decapping and 5'-->3' exonucleolytic digestion. An important question involves the mechanisms that allow particular mRNAs to exhibit different rates of both deadenylation and decapping. Since the cap structure plays a critical role in the assembly of translation initiation factors, we hypothesized that the status of the cytoplasmic cap binding complex would affect the rate of decapping. To test this hypothesis, we examined mRNA decay rates in yeast strains that were defective in several translation initiation factors that are part of the cap binding complex. These experiments yielded three significant observations. First, any mutation known to inhibit translation initiation also increased the rate of decapping. Second, decapping still occurred only after deadenylation, suggesting that the ability of the poly(A) tail to inhibit decapping does not require efficient translation of the transcript. Third, mutants with defects in translation initiation factors also showed an increase in the rate of deadenylation, suggesting that the rate of deadenylation may be controlled primarily by the translation status of the transcript. These results argue that the nature of the translation initiation complex is a critical factor in determining the mRNA half-life. This view also implies that some cis-acting sequences that modulate mRNA decay rate do so by affecting the translation status of the transcript.

Endoribonucleases↗

PubMed1985

A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisiae.

The GCN4 gene encodes a positive effector of amino acid biosynthetic genes in Saccharomyces cerevisiae. Genetic analysis has suggested that GCN4 is regulated by a hierarchy of interacting positive and negative effectors in response to amino acid starvation. Results presented here for a GCN4-lacZ gene fusion support this regulatory model and suggest that the regulators of GCN4 exert their effects primarily at the level of translation of GCN4 mRNA. Both the GCN2 and GCN3 products appear to stimulate translation of GCN4 mRNA in response to amino acid starvation, because a recessive mutation in either gene blocked derepression of GCN4-lacZ fusion enzyme levels but did not reduce the fusion transcript level relative to that in wild-type cells grown in the same conditions. The GCD1 product appears to inhibit translation of GCN4 mRNA because under certain growth conditions, the gcd1-101 mutation led to derepression of the GCN4-lacZ fusion enzyme level in the absence of any increase in the fusion transcript level. In addition, the gcd1-101 mutation suppressed the low translational efficiency of GCN4-lacZ mRNA observed in gcn2- and gcn3- cells. A deletion of four small open reading frames in the 5' leader of GCN4-lacZ mRNA mimicked the effect of a gcd1 mutation and derepressed translation of the fusion transcript in the absence of either starvation conditions or the GCN2 and GCN3 products. By contrast, in a gcd1- strain, the deletion resulted in little additional increase in the translational efficiency of the fusion transcript. These results suggest that GCD1 mediates the translational repression normally exerted by the GCN4 leader sequences and that GCN2 and GCN3 antagonize these negative elements in response to amino acid starvation. The effects of the trans-acting mutations on the translation of GCN4-lacZ mRNA remained intact even when transcription of the fusion gene was placed under the control of the S. cerevisiae GAL1 transcriptional control element.

Amino Acids↗

PubMed2004

Issues and challenges of instrument translation.

The purpose of this article was to discuss the challenges of instrument translation, using the translation of the Medical Outcomes Study Social Support Survey into Chinese as an example. Brislin's model of translation, which highlights the need for forward and backward translation, was used. Major considerations in conducting translation, and the strategies used to overcome the challenges arising from cultural and linguistic differences between the source and target languages, were discussed. Examples were used to illustrate how difficulties, such as maintenance of the original intent of the questionnaire, maximization of the cultural relevancy of the concept in question, and enhancement of the comprehensibility of the translated questionnaire, were handled. The importance of literal and cultural adaptation of a developed instrument, rather than its simple word translation in the maintenance of an equivalent translation is highlighted.

Attitude to Health↗

PubMed2004

[Translation and cultural adaptation of the quality of life assessment instrument for chronic renal patients (KDQOL-SF)].

BACKGROUND: The objective of this study was to translate from English into Portuguese and to perform cultural adaptation of the Kidney Disease Quality of Life Short Form--KDQOL-SF to make possible its validation in Brazil. METHODS: This instrument was translated from the original English version into Portuguese language by the authors and it was also translated by a certified translator and revised by a specialized translator who evaluated the level of difficulty for translation. Thirty end-stage renal disease patients undergoing dialysis were randomly selected to participate in the study. RESULTS: The mean age of patients was 47 +/- 9 years (23 to 60 yr), and the predominant education level was incomplete elementary school (1st to 8th grade=53%); 60% of the patients were female. The majority of patients (63%) were undergoing hemodialysis and the period of treatment within the last 30 days was 12 hours or more per week. The time of dialysis treatment was 0-2 years for 70% of the patients. The feasibility of the instrument and the difficulties found by the patients were evaluated by a panel of experts and changes were made regarding difficulties of comprehension. Some activities were substituted since they were not regular for the Brazilian population. There were modifications in expressions of translation for terms suggested by patients and Brazilian experts and, for five items it was suggested to include an explanation in parentheses. Common words used in the Portuguese language were chosen. CONCLUSIONS: The translation and cross-cultural adaptation of the KDQOL questionnaire to Portuguese were concluded, having been accomplished this important stage for its validation and use in our environment.

Adult↗

PubMed2004

Chronic liver disease questionnaire: translation and validation in Thais.

AIM: Quality of life (QOL) is a concept that incorporates many aspects of life beyond "health". The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL. The objectives of this study were to translate and validate a liver specific questionnaire, the CLDQ. METHODS: The CLDQ was formally translated from the original version to Thai language with permission. The translation process included forward translation, back translation, cross-cultural adaptation and a pretest. Reliability and validity of the translated version was examined in CLD patients. Enrolled subjects included CLD and normal subjects with age- and sex-matched. Collected data were demography, physical findings and biochemical tests. All subjects were asked to complete the translated versions of CLDQ and SF-36, which was previously validated. Cronbach's alpha and test-retest were performed for reliability analysis. One-way Anova or non-parametric method was used to determine discriminant validity. Spearman's rank correlation was used to assess convergent validity. P -value <0.05 was considered statistically significant. RESULTS: A total of 200 subjects were recruited into the study, with 150 CLD and 50 normal subjects. Mean ages (SD) were 47.3(11.7) and 49.1(8.5) years, respectively. The number of chronic hepatitis: cirrhosis was 76:74, and the ratio of cirrhotic patients classified as Child A:B:C was 37(50%): 26(35%): 11(15%). Cronbach's alpha of the overall CLDQ scores was 0.96 and of all domains were higher than 0.93. Item-total correlation was >0.45. Test-retest reliability done at 1 to 4 wk apart was 0.88 for the average CLDQ score and from 0.68 to 0.90 for domain scores. The CLDQ was found to have discriminant validity. The highest scores of CLDQ domains were in the normal group, scores were lower in the compensated group and lowest in the decompensated group. The significant correlation between domains of the CLDQ and SF-36 was found. The average CLDQ score was strongly correlated with the general health domain of SF-36. (P=0.69: P=0.01). CONCLUSION: The translated CLDQ is valid and applicable in Thais with CLD. CLDQ reveals that QOL in these patients is lower than that in normal population. QOL is more impaired in advanced stage of CLD.

Adult↗

PubMedDate not supplied

[Formal thought disorders: French translation of the Thought, Language and Communication assessment scale].

This article proposes a french translation of Andreasen's Thought, Language and Communication (TLC) scale (Andreasen, 1979). This scale is widely used in current literature and remains a reference due to the fact that it has made it possible to establish a consensus with regard to formal thought disorders and has contributed to the operationalisation of the concept of dissociation. This scale consists of 18 items. Each item is clearly defined through the use of clinical examples, rated from 0 to 4 as a function of the intensity of the disorder (absent, slight, medium, severe, extreme). The interview conditions are also stated: free interview of minimum 10 minutes followed by a more structured interview. Some items of the TLC are taken directly from the SANS and SAPS. Their translation has been taken over from french translations already validated by Lecrubier and Boyer (1987). The others were translated within the department and have been verified by a native English speaker. The entirely of the translation has been verified by Andreasen. The metrological qualities of this french translation have been studied in a population of 107 schizophrenic patients who fulfilled all the DSM IV criteria: 73 males and 34 females, mean age 33.4 9 years, in or outpatients, all under neuroleptic treatment and all evaluated by an experienced clinician. Thirty one patients have been filmed to assess the interjudge reliability. The results indicate a high level of interjudge consistency (interclass correlation coefficient 0.96). The global score was 17 9.4. In the factorial analysis before rotation we observe a main factor that makes it possible to calculate a global score. The results of factor analysis of the TLC variables after rotation yield five factors that have an eigen value greater than 1. These five factors explain 66% of the variance. All items have a weight greater than 0.45. The first factor includes Poverty of content speech, Tangentiality, Derailment, Incoherence, Illogical thinking, Loss of goal and Perseveration. It reflects thinking disorganisation. The second factor includes Pressure of speech, Circumstantiality, Self reference and Poverty of speech (negative weight). This factor reflects verbal production. The third factor is composed of Clanging, Neologisms, Word approximation and Echolalia. This factor reflects verbal structure. The fourth factor is only composed of Stilted speech and the fifth one composed of Distractible speech and Blocking. These data have been compared to those reported in the literature: Andreasen in 1979 (113 patients: 32 suffering from manic disorder, 36 from depressive disorder and 45 schizophrenic disorder) and in 1986 (194 subjects: 94 controls, 25 suffering from manic disorder, 25 schizoaffective disorder and 50 schizophrenic patients), Harvey in 1992 (115 schizophrenic patients) and Peralta in 1992 (142 schizophrenic patients). Response levels for each item of the TLC french translation were very close to those found in the english versions. Differences in scores can be explained by clinical differences between populations studied. Factorial analyses also correspond well to such versions. In particular, after rotation, the three factorial subscores found representative of disorganisation, verbal production and verbal structure respectively are closed to those proposed by the english versions. In conclusion, the translation of Andreasen's Thought, Language and Communication (TLC) scale (Andreasen 1979) that we propose here therefore appears to exhibit metrological qualities sufficiently close to those reported in literature to permit its generalised use in France.

Adult↗

PubMed1992

Post-translational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for their activation of NADPH oxidase.

rac1 and rac2 p21s are ras p21-like small GTP-binding proteins which are implicated in the NADPH oxidase-catalyzed superoxide generation in phagocytes. rac1 and rac2 p21s have a Cys-A-A-Leu (A = aliphatic amino acid) structure in their C-terminal region which may undergo post-translational processing including prenylation, proteolysis, and carboxyl methylation. We studied the function of this post-translational processing of rac p21s in their interaction with the stimulatory and inhibitory GDP/GTP exchange proteins for rac p21s, named smg GDS and rho GDI, and in their NADPH oxidase activation. We produced human recombinant rac1 and rac2 p21s in insect cells and purified them from the membrane and soluble fractions as the post-translationally processed and unprocessed forms, respectively. Post-translationally processed rac1 and rac2 p21s were sensitive to both smg GDS and rho GDI, but post-translationally unprocessed rac1 and rac2 p21s were insensitive to them. The GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-bound form of post-translationally processed rac1 and rac2 p21s stimulated the NADPH oxidase activity, but post-translationally unprocessed rac1 and rac2 p21s were far less effective. These results indicate that both rac1 and rac2 p21s stimulate the NADPH oxidase activity and that their post-translational processing is important not only for their interaction with smg GDS and rho GDI but also for their NADPH oxidase activation.

Amino Acid Sequence↗

PubMed2004

Experiments in cross-language medical information retrieval using a mixing translation module.

Given the ever-increasing scale and diversity of medical literature widely published in English on the Internet, improving the performance of information retrieval by cross-language is an urgent research objective. Cross-language medical information retrieval (CLMIR) consists of providing a query in one language and searching medical document collections in one or more different languages. Our users of CLMIR are users who are able to read biomedical texts in English, but have difficulty formulating English queries. This paper proposes a French/English CLMIR system as a mixing model for supporting the retrieval of English medical documents. Methods fall into the category of query translation approach in which we use a hybrid machine translation that combines a pattern-based module with a rule-based translator and includes three steps from pre- to- post-translation. In parallel to this hybrid machine translation, we use multilingual UMLS Methasaurus as a complementary translator. The results show that using a mixing translation module outperforms machine translation-based method and thesaurus-based method used separately.

Information Storage and Retrieval↗

PubMed2006

[Questionnaires on the quality of life in other than the Dutch language used in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine): the translation procedure and arguments for the choice of the questionnaire].

OBJECTIVE: To determine how the authors of research published in the Nederlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine; NTvG) translated the questionnaires that they used in other than the Dutch language and to review the arguments on the basis of which the authors chose the questionnaires used. DESIGN: Bibliometric study and a survey. METHOD: All of the authors who had published an article in the NTvG up to and including January 2006 in which a questionnaire was used that was originally not in the Dutch language were approached by means ofa survey. In this survey, they were asked about the translation procedure and the factors that had contributed to the choice of the particular questionnaire. RESULTS: The authors of 38 articles in which a translated non-Dutch questionnaire had been used returned 31 survey forms (response: 82%). Among the 31 authors, who had used a total of 39 questionnaires, 24 (77%) were aware of the proper translation procedure. Of the 9 authors who had translated the questionnaire themselves, 6 had used the technique of translation and back-translation. In the choice of the questionnaire used, an important factor for many authors (64%) was the use of the questionnaire in previously published comparable research. CONCLUSION: A large proportion of the authors (77%) was aware of the current guidelines for the translation of questionnaires.

Bibliometrics↗

PubMed1991

Quantitative evaluation of English-Japanese machine translation of medical literature.

Although many machine-translation programs are currently available, few evaluation methods of such translation exist for any given application area. It is difficult to evaluate machine-translation systems objectively because the quality of a translation depends on the combination of three factors: the translation program, the dictionary, and the original document. In this study, we developed a quantitative evaluation method for assessing machine translation, which evaluates these three factors separately. We applied this method to the translation of English to Japanese for medical literature and the method proved to be a good indicator for further system improvement. Using this method we also discovered other important points for machine translation, such as the examination of target documents for the construction of a better application dictionary.

Computers↗

PubMed1985

Post-translational import of fatty acyl-CoA oxidase and catalase into peroxisomes of rat liver in vitro.

Total polysomal RNA of rat liver was translated in vitro in a rabbit reticulocyte lysate system. The translation products were mixed with a postnuclear supernatant fraction of rat liver and incubated post-translationally at 26 degrees C for 15-60 min. The import assay mixture was separated into a particulate fraction and supernatant by centrifugation, both of which were analyzed by immunoprecipitation with a goat antibody against rat liver peroxisomal proteins, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography. One peroxisomal translation product (Mr 72,000) appeared in the particulate fraction, was partly proteinase K-resistant, and addition of detergents prior to proteolysis abolished this resistance. In isopycnic centrifugation of the uptake assay mixture, the protease-resistant 35S-polypeptide of Mr 72,000 cosedimented with the peroxisomes. This translation product was identified immunochemically as fatty acyl-CoA oxidase; both before and after import it was indistinguishable in size from subunit A of the purified enzyme by prolonged sodium dodecyl sulfate-polyacrylamide gel electrophoresis. When the cell-free translation products were incubated with highly purified peroxisomes, 35S-catalase entered peroxisomes (by the criterion of protease resistance), and its entry was stimulated by the addition of a high speed supernatant (cytosolic) fraction of rat liver. These results demonstrate the post-translational import into peroxisomes in vitro of at least two cell-free translation products.

Acyl-CoA Oxidase↗

PubMed1991

Sequence elements that affect mRNA translational activity in developing Dictyostelium cells.

Post-transcriptional controls, including changes in both mRNA translational activity and stability, play an important role in the regulation of ribosomal protein gene expression in developing Dictyostelium discoideum cells. Previously we have shown that the mechanisms which regulate the translational activity of the r-protein mRNAs operate at the level of translational initiation and do not involve changes in polyadenylation or capping. By analysing the translational behavior of chimeric and mutant mRNAs in transformed cells, we have now been able to localize the determinants of translational activity of one of the r-protein mRNAs to the 5'-untranslated region. Although this and other r-protein mRNAs differ strikingly from the Dictyostelium consensus in the region of the initiator AUG codon, we find that improving the match to that consensus does not increase the translational activity of the message in developing cells. Current experiments are designed to determine whether translational regulation is mediated by strong interactions with specific inhibitors or by weak interactions with translational initiation factors.

Base Sequence↗

PubMed1983

Translational products of mRNAs coding for non-epidermal cytokeratins.

Total RNA and poly(A)+ RNA were isolated from tissues and cultured cells of various mammalian species (bovine muzzle epidermis and bladder urothelium; rat hepatoma cells; human cell lines HeLa, MCF-7 and A-431) and examined by translation in vitro using the reticulocyte lysate system. Polypeptides were separated and identified by two-dimensional electrophoresis and cytokeratins were selectively enriched from the translation assays by co-polymerization with added heterologous cytokeratins. In all three species, non-epidermal cytokeratins A, D and mol. wt. 40,000 (corresponding to numbers 8, 18 and 19 of the human cytokeratin catalog of Moll et al., 1982) were identified as translation products capable of co-polymerization with epidermal keratins. Several other basic and other acidic cytokeratins were also identified as translational products. In addition, two unidentified polypeptides (mol. wt. 52,000 and 43,000) which were minor polypeptides in cytoskeletons and translation assays were found to be specifically enriched in co-polymers with bovine epidermal keratins. The results indicate that many, perhaps all, non-epidermal cytokeratins characteristic of simple epithelia are genuine products of translation and that their diversity is not due to post-translational modification or processing. These findings, taken together with observations of in vitro translation of epidermal mRNAs, suggest that the diversity of cell type-specific expression of the different members of the cytokeratin polypeptide family is largely due to the cell type-specific synthesis of diverse mRNAs.

Animals↗

PubMed1992

Replication control of plasmid R1: RepA synthesis is regulated by CopA RNA through inhibition of leader peptide translation.

The replication frequency of plasmid R1 is post-transcriptionally controlled by an antisense RNA, CopA, that binds to the leader region in the RepA mRNA, CopT, and ultimately inhibits the synthesis of the replication initiator protein RepA. We present results demonstrating that CopA controls RepA synthesis indirectly. A reading frame for a 24 amino acid leader peptide (Tap, translational activator peptide) is located in the region between the copA and repA genes. A translational fusion between the tap and lacZ genes was used to demonstrate that tap is translated and controlled by CopA. Stop codons (UAA, UAG and UGA) introduced at three different positions within the tap gene led to a severe decrease in repA expression. Specific suppression of the stop codons reversed the effect. This indicates that tap translation is required for RepA synthesis. Phylogenetic comparisons between IncFII-like plasmids, together with previous in vitro and in vivo results (Ohman and Wagner, 1989, 1991), suggest that a stable RNA stem-loop structure sequesters the repA ribosome binding site irrespective of CopA-CopT duplex formation. The results presented here show that ribosomes translating the tap reading frame have to terminate close to the start codon of repA to permit reinitiation (direct translational coupling), and that transient disruption of the inhibitory RNA stem-loop is insufficient for activation of repA translation. The possibility that direct translational coupling is required because of a suboptimal repA RBS cannot be excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗

PubMed1993

Non-standard translational events in Candida albicans mediated by an unusual seryl-tRNA with a 5'-CAG-3' (leucine) anticodon.

From in vitro translation studies we have previously demonstrated the existence of an apparent efficient UAG (amber) suppressor tRNA in the dimorphic fungus Candida albicans (Santos et al., 1990). Using an in vitro assay for termination codon readthrough the tRNA responsible was purified to homogeneity from C.albicans cells. The determined sequence of the purified tRNA predicts a 5'-CAG-3' anticodon that should decode the leucine codon CUG and not the UAG termination codon as originally hypothesized. However, the tRNA(CAG) sequence shows greater nucleotide homology with seryl-tRNAs from the closely related yeast Saccharomyces cerevisiae than with leucyl-tRNAs from the same species. In vitro tRNA-charging studies demonstrated that the purified tRNA(CAG) is charged with Ser. The gene encoding the tRNA was cloned from C.albicans by a PCR-based strategy and DNA sequence analysis confirmed both the structure of the tRNA(CAG) and the absence of any introns in the tRNA gene. The copy number of the tRNA(CAG) gene (1-2 genes per haploid genome) is in agreement with the relatively low abundance (< 0.5% total tRNA) of this tRNA. In vitro translation studies revealed that the purified tRNA(CAG) could induce apparent translational bypass of all three termination codons. However, peptide mapping of in vitro translation products demonstrated that the tRNA(CAG) induces translational misreading in the amino-terminal region of two RNA templates employed, namely the rabbit alpha- and beta-globin mRNAs. These results suggest that the C.albicans tRNA(CAG) is not an 'omnipotent' suppressor tRNA but rather may mediate a novel non-standard translational event in vitro during the translation of the CUG codon. The possible nature of this non-standard translation event is discussed in the context of both the unusual structural features of the tRNA(CAG) and its in vitro behaviour.

Anticodon↗

PubMed2000

Significance of changes in the reference position for measurements of tibial translation and diagnosis of cruciate ligament deficiency.

Measurements of tibial translation in response to an external load are used in clinical and laboratory settings to diagnose and characterize knee-ligament injuries. Before these measurements can be quantified, a reference position of the knee must be established (defined as the position of the knee with no external forces or moments applied). The objective of this study was to determine the effects of cruciate ligament deficiency on this reference position and on subsequent measurements of tibial translation and, in so doing, to establish a standard of kinematic measurement for future biomechanical studies. Thirty-six human cadaveric knees were studied with a robotic/universal force-moment sensor testing system. The reference positions of the intact and posterior cruciate ligament-deficient knees of 18 specimens were determined at full extension and at 30, 60, 90, and 120 degrees of flexion, and the remaining five-degree-of-freedom knee motion was unrestricted. Subsequently, under a 134-N anterior-posterior load, the resulting knee kinematics were measured with respect to the reference positions of the intact and posterior cruciate ligament-deficient knees. With posterior cruciate ligament deficiency, the reference position of the knee moved significantly in the posterior direction, reaching a maximal shift of 9.3 +/- 3.8 mm at 90 degrees of flexion. For the posterior cruciate ligament-deficient knee, posterior tibial translation ranged from 13.0 +/- 3.4 to 17.7 +/- 3.6 mm at 30 and 90 degrees, respectively, when measured with respect to the reference positions of the intact knee. When measured with respect to the reference positions of the posterior cruciate ligament-deficient knee, these values were significantly lower, ranging from 11.7 +/- 4.3 mm at 30 degrees of knee flexion to 8.4 +/- 4.8 mm at 90 degrees. A similar protocol was performed to study the effects of anterior cruciate ligament deficiency on 18 additional knees. With anterior cruciate ligament deficiency, only a very small anterior shift in the reference position was observed. Overall, this shift did not significantly affect measurements of tibial translation in the anterior cruciate ligament-deficient knee. Thus, when the tibial translation in the posterior cruciate ligament-injured knee is measured when the reference position of the intact knee is not available, errors can occur and the measurement may not completely reflect the significance of posterior cruciate ligament deficiency. However, there should be less corresponding error when measuring the tibial translation of the anterior cruciate ligament-injured knee because the shift in reference position with anterior cruciate ligament deficiency is too small to be significant. We therefore recommend that in the clinical setting, where the reference position of the knee changes with injury, comparison of total anterior-posterior translation with that of the uninjured knee can be a more reproducible and accurate measurement for assessing cruciate-ligament injury, especially in posterior cruciate ligament-injured knees. Similarly, in biomechanical testing where tibial translations are often reported for the ligament-deficient and reconstructed knees, a fixed reference position should be chosen when measuring knee kinematics. If such a standard is set, measurements of knee kinematics will more accurately reflect the altered condition of the knee and allow valid comparisons between studies.

Anterior Cruciate Ligament Injuries↗