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PubMed1995

Modular unipolar versus bipolar prosthesis: a prospective evaluation of functional outcome after femoral neck fracture.

Between January 1, 1987, and December 31, 1992, 140 community-dwelling geriatric patients > or = 65 years of age with a displaced femoral neck fracture (Garden III-IV) underwent primary prosthetic replacement and were followed prospectively for a minimum of 1 year. Overall, 92 patients received a cemented bipolar prosthesis and 48 patients received a cemented modular unipolar prosthesis. There were no statistically significant differences between the two groups with respect to preinjury characteristics (age, sex, and number and severity of medical comorbidities) and functional ability. There were no statistically significant differences between the two groups with regard to the number of postoperative complications, length of stay, and 1 year mortality rate. An in-depth functional evaluation was obtained as follows: level of ambulation, independence in basic activities of daily living (feeding, bathing, dressing, toileting), and independence in instrumental activities of daily living (food shopping, food preparation, banking, laundry, housework, and use of public transportation). At 1 year follow-up, no statistically significant differences in functional ability were identified between the unipolar and bipolar groups. Furthermore, at a minimum of 1 year follow-up, there were no statistically significant differences between the two groups with regard to the need for revision surgery or the incidence hip pain. Based on the results of this study, there does not appear to be any advantage to the use of bipolar endoprosthesis for the treatment of femoral neck fractures in the elderly patient. The lower cost of modular unipolar prostheses compared with bipolar prostheses provides additional support for their use.

Aged↗

PubMed2000

Clinical and finite element analysis of a modular femoral prosthesis consisting of a head and stem component in the treatment of pertrochanteric fractures.

OBJECTIVE: To determine the biomechanical characteristics and potential clinical efficacy of a cementless modular femoral prosthesis consisting of a variable head (50 to 80 millimeters) and stem (length 120 to 280 millimeters, diameter 10 to 20 millimeters) component in patients with pertrochanteric femoral fracture. DESIGN: Finite element analysis (FEA) of different lengths and diameters of prosthesis components and first clinical prospective study in pertrochanteric femoral fracture. METHOD: Using a 3D-CAD program, a model of femoral cortical bone with a pertrochanteric fracture was created and combined with a model of the prosthesis. This model was transferred into an FEA program. After applying a torsion-bending load of 2,000 N (25 degrees, 45 degrees) on the prosthesis, stress distribution in the cortical bone was determined for different lengths (160 to 240 millimeters) and diameters (10 and 12 millimeters) of stem. PATIENTS: Twenty-eight patients with pertrochanteric fractures (very unstable or osteoarthritis) were treated with a modular hip arthroplasty. Complications, fracture healing, and results at first follow-up (average 13 months) were determined. RESULTS: FEA analysis indicated that reduction in stress was less when a prosthesis with a short stem was used. Shear stress in the interface bone/prosthesis was not affected by stem length. Prostheses with thin stems produced higher sheer stresses than those with thick stems. Results of FEA were used as the basis for clinical application of the device. None of the patients died, and all patients were able to walk, although some needed a cane or walker after surgery. There was no increase in thigh pain compared with reported pretrauma levels. Radiographs showed subsidence of up to 5 millimeters in 20 percent of patients. However, all but one prosthesis was stable at follow-up. Fracture healing was achieved in all patients. CONCLUSIONS: If proximal fixation of a femoral uncemented stem cannot be achieved, stem diameter should provide maximum cortical contact to reduce sheer stress. Longer stems do not necessarily provide additional stability. By using this prosthesis and selection method, a good outcome at first follow-up was observed.

Activities of Daily Living↗

PubMed2000

Hybrid external fixation in high-energy elbow fractures: a modular system with a promising future.

BACKGROUND: Severe, high-energy, periarticular elbow injuries producing a "floating joint" are a major surgical challenge. Their reconstruction and rehabilitation are not well documented. Therefore, the following reports our experience with treating such injuries caused by war wounds. METHODS: Seven adults with compound open peri- and intra-articular elbow fractures were treated in hybrid ring tubular fixation frames. After debridement, bone stabilization, and neurovascular reconstructions, early controlled daily movements were started in the affected joint. RESULTS: These seven patients had together seven humeral, five radial, and six ulnar fractures. All fractures united at a median time of 180 days. No deep infection developed. The functional end results assessed by the Khalfayan functional score were excellent in two, good in one, and fair in four of these severely mangled upper extremities. None was amputated. CONCLUSIONS: The Mangled Extremity Severity Score has been shown to be unable to provide a reliable assessment for severe high-energy limb injuries surgically managed with the modular hybrid thin wire tubular external fixation system. This hybrid system is a very useful addition to the surgical armamentarium of orthopedic trauma surgeons. It both allows complex surgical reconstructions and reduces the incidence of deep infections in these heavily contaminated injuries. The hybrid circular (thin wire) external fixation system is very modular and may provide secure skeletal stabilization even in cases of severely comminuted juxta-articular fractures on both sides of the elbow joint (floating elbow) with severe damage to soft tissues. This fixation system allows individual fixation of forearm bone fractures, thus allowing the preservation of pronation-supination movements.

Adult↗

PubMed2003

Partial outlet obstruction enhances modular autonomous activity in the isolated rat bladder.

PURPOSE: Autonomous bladder activity can take the form of localized micromotions (MMs), suggesting that the detrusor may be arranged into component modules, of which each is capable of contracting autonomously. We examined MMs in isolated whole rat bladder and the effects of partial bladder outlet obstruction as a model of detrusor overactivity (DO) to ascertain whether altered modular activity could be an etiological factor in DO. MATERIALS AND METHODS: A total of 12 adult female Sprague-Dawley rats underwent obstruction or sham operation for 1 or 4 weeks. Bladders were microsurgically removed and mounted in whole organ tissue baths. Recordings of intravesical pressure and simultaneous registration of intramural contractions were performed under standardized conditions. RESULTS: Prior to filling MMs took the form of localized contractions near the vesicoureteral junction in sham operated animals and multifocal microcontractions in obstructed animals. Intravesical volume increases were associated with a change in localized MMs to propagated contraction waves. In sham operated animals stretch resulted in increased MM frequency but decreased amplitude. After obstruction stretch elicited highly coordinated MMs and enhanced intravesical pressure transmission. The time since surgery did not alter observations in the sham or obstructed group. CONCLUSIONS: Detrusor muscle in isolated bladders under conditions modeling urine storage may have a functional modular arrangement with the basolateral region most active prior to filling. Peripheral factors determining intravesical pressure include the number of modules active, coordination and intramural tension at other sites. After bladder outlet obstruction more modules are active at baseline and their coordination is enhanced by stretch, leading to increased pressure fluctuations. Such changes may contribute to the development of DO.

Animals↗

PubMed1998

The autonomy of the visual systems and the modularity of conscious vision.

Anatomical and physiological evidence shows that the primate visual brain consists of many distributed processing systems, acting in parallel. Psychophysical studies show that the activity in each of the parallel systems reaches its perceptual end-point at a different time, thus leading to a perceptual asynchrony in vision. This, together with clinical and human imaging evidence, suggests strongly that the processing systems are also perceptual systems and that the different processing-perceptual systems can act more or less autonomously. Moreover, activity in each can have a conscious correlate without necessarily involving activity in other visual systems. This leads us to conclude not only that visual consciousness is itself modular, reflecting the basic modular organization of the visual brain, but that the binding of cellular activity in the processing-perceptual systems is more properly thought of as a binding of the consciousnesses generated by each of them. It is this binding that gives us our integrated image of the visual world.

Animals↗

PubMed2000

Primary sequence and enzymic properties of two modular endoglucanases, Cel5A and Cel45A, from the anaerobic fungus Piromyces equi.

Two endoglucanase cDNAs, designated cel5A and cel45A, were isolated from a cDNA library of the anaerobic fungus Piromyces equi. Sequence analysis revealed that cel5A has an open reading frame of 5142 bp and encodes a 1714 amino acid modular enzyme, Cel5A, with a molecular mass of 194847 Da. Cel5A consists of four catalytic domains homologous to family-5 glycosyl hydrolases, two C-terminal dockerins and one N-terminal dockerin. This is the first report of a complete gene containing tandem repeats of family-5 catalytic domains. The cDNA cel45A has an open reading frame of 1233 bp and encodes a 410 amino acid modular enzyme, Cel45A, with a molecular mass of 44380 Da. The catalytic domain, located at the C terminus, is homologous to the family-45 glycosyl hydrolases. Cel45A is the first family-45 enzyme to be described in an anaerobe. The presence of dockerins at the N and C termini of Cel5A and at the N terminus of Cel45A implies that both enzymes are part of the high-molecular-mass cellulose-degrading complex produced by Piromyces equi. The catalytic domain nearest the C terminus of Cel5A and the catalytic domain of Cel45A were hyperexpressed as thioredoxin fusion proteins, Trx-Cel5A' and Trx-Cel45A', and subjected to biochemical analysis. Trx-Cel5A' has a broad substrate range, showing activity against carboxymethylcellulose, acid-swollen cellulose, barley beta-glucan, lichenin, carob galactomannan, p-nitrophenyl beta-D-cellobiopyranoside and xylan. Trx-Cel45A' is active against carboxymethylcellulose, acid-swollen cellulose and the mixed linkage glucans, barley beta-glucan and lichenin.

Amino Acid Sequence↗

PubMed1990

Construction of modular circuits in the mammalian brain.

Comparison of seemingly different modular units in the mammalian brain raises the possibility of a common mechanism for their formation: the growth of neuropil mediated by trophic interactions. The ongoing postnatal construction of modular circuits according to trophic interplay may in turn account for the remarkable plasticity of the juvenile brain. By the same token, the normal waning of circuit construction during postnatal development may explain the end of critical periods, the diminished ability to recover from injury in older animals, and the decline with increasing age in the ability of mammals to learn complex skills.

Animals↗

PubMed1996

Modular nature of abscisic acid (ABA) response complexes: composite promoter units that are necessary and sufficient for ABA induction of gene expression in barley.

The modular nature of the abscisic acid response complex (ABRC), the promoter unit necessary and sufficient for abscisic acid (ABA) induction of gene expression in barley, is defined in this study. We investigated ABA induction of a barley late embrogenesis abundant (Lea) gene, HVA1, and found that the ABRC of this gene consists of a 10-bp box with an ACGT core (ACGT-box) and the 11 bp directly upstream, named coupling element 3 (CE3). Only one copy of this ABRC is sufficient to confer ABA induction when linked to a minimal promoter. Because we previously reported another ABRC in the barley HVA22 gene, which consists of an ACGT-box with a distal coupling element (CE1), exchange experiments were conducted to study the interaction among modular elements in these ABRCs. We show that ACGT-boxes in these ABRCs are interchangeable, indicating that an ACGT-box can interact with either a distal or a proximal coupling element to confer ABA response. However, the two coupling elements are not fully exchangeable. Although CE3 can function either proximal or distal to the ACGT-box, CE1 is only functional at the distal position. The presence of both the distal and the proximal coupling elements has a synergistic effect on the absolute level of expression as well as on ABA induction. These ABRCs function in both seed and vegetative tissues. In seeds, ABA induction of the ABRC containing the proximal CE3, but not the ABRC with the distal CE1, is enhanced in the presence of the transcription regulator Viviparous1, indicating that these two ABRCs are mediated by different ABA signal transduction pathways.

Abscisic Acid↗

PubMed2001

New tools for studying integration and modularity.

The study of phenotypic integration concerns the modular nature of organismal phenotypes. The concept provides a rationale for why certain subsets of phenotypic traits show particularly high levels of association over development and/or evolution. The techniques detailed in this report facilitate the generation and testing of hypotheses of phenotypic integration and trait interaction. The approach advocated for exploring patterns of interaction among traits is based on the statistical notion of conditional independence, incorporated in a technique known as graphical modeling. The use of graphical models is illustrated with an application to a well-known biological dataset of fowl skeletal measurements, previously analyzed by Sewall Wright. A definition of phenotypic modularity is given, based on a notion of mutual information, which provides a consistent criterion for recognizing and delimiting integrated subsets of traits and which can be related to standard models of multivariate selection.

Analysis of Variance↗

PubMed1975

The Denver universal microspectroradiometer (DUM). II. Computer configuration and modular programming for radiometry.

This paper describes and discusses for microscopists and spectroscopists the choice of computer equipment and the design of programs used in the Denver Universal Microspectroradiometer (DUM). This instrument is an accurate computerized photon-counting microspectrophotometer, microspectrofluorimeter and microrefractometer. The computer is used to control the operation of the system, to acquire radiometric data of various kinds, and to reduce, analyse and output the data in a readily usable form. Since the radiometer was designed to carry out many kinds of measurements in a variety of micro- and macroscopic specimens, and since different methods of microscopy or spectroscopy have to be combined in various ways fro the study of any one specimen, no single master-program could fulfill efficiently all foreseeable requirements. Therefore, the programming developed is interactive, modular, hierarchical and hybrid. Modular interactive programming makes it possible for almost any kind of main program, applicable to almost any kind of measurement, to be assembled quickly from a collection of hierarchical subroutines. Main programs are short and composed mainly of Fortran statements calling subroutines; subroutines, in turn, automatically call other subroutines over many levels. The subroutines are independently written and optimized for maximum operational efficiency in the computer system used, or for maximum ease of transfer to other systems. This approach to programming enables someone unfamiliar with computer languages to operate the radiometric system from the console of the CRT terminal. The writing of new main programs, by linking groups of existing subroutines, requires only a minimum acquaintance with Fortran; only the writing and revision of subroutines requires programming experience. Differences and similarities in the method of computer operation between the present system and other computerized radiometers are briefly discussed.

Computers↗

PubMed1996

A secreted protein tyrosine phosphatase with modular effector domains in the bacterial pathogen Salmonella typhimurium.

A number of bacterial pathogens have evolved sophisticated strategies to subvert host-cell signal-transduction pathways for their own benefit. These bacteria produce and export proteins capable of specific interactions with key mammalian cell regulatory molecules in order to derail the normal functions of the cells. In this study, we describe the identification of a modular effector protein secreted by the bacterial pathogen Salmonella typhimurium that is required for its full display of virulence. Sequence analysis revealed that a carboxy-terminal region of this protein, which we have termed SptP, is homologous to the catalytic domains of protein tyrosine phosphatases. Purified SptP protein efficiently dephosphorylated peptide substrates phosphorylated on tyrosine. An engineered mutant of SptP in which a critical Cys residue in the catalytic domain was changed to Ser was devoid of phosphatase activity, indicating a catalytic mechanism similar to that of other tyrosine phosphatases. In addition, an amino-terminal region of SptP exhibited sequence similarity to the ribosyltransferase exoenzyme S from Pseudomonas aeruginosa and the cytotoxin YopE from Yersinia spp. The modular nature of this effector protein may allow multiple interactions with host-cell signalling functions.

Amino Acid Sequence↗

PubMed1993

Management of chondrosarcoma including modular ceramic and alumina prosthetic replacement.

Forty-one cases of chondrosarcoma from varying sites throughout the body, and treated exclusively by one of the authors (R.L.H.) from 1972 to 1990 were reviewed. The symptoms, signs, location of tumours, treatment and progress are presented. Particular attention was paid to modular bone replacement techniques. Excision and reconstruction of the bone or joint were carried out in 17 femora, five tibia and six humeri. Comparison between this method of management and other techniques is discussed. Titanium and alumina prostheses for the hip, femur, tibia, shoulder and humerus have been designed by the senior author. These are both inert and modular, and have been found to be superior to other methods of treatment in both function and cosmesis. They do not possess the same potential donor infection risks and other disadvantages of allograft replacement. Immediate postoperative weight bearing and mobilization are possible with these systems. The Huckstep prostheses allow for bony ingrowth into their porous coated alumina sleeves, spacers and stems. In addition, the titanium alloy locking component for the femoral stems has an elasticity half that of other metal alloys and this was found to minimize stress shielding.

Adult↗

PubMed1994

The functional evaluation of patients with primary malignant tumours about the knee treated by modular endoprosthetic replacement.

Between 1985 and 1992, 39 patients with primary malignant neoplasms about the knee presented to the musculoskeletal oncology service at the Royal Prince Alfred Hospital, Sydney. Twenty-eight patients met the criteria for limb salvage surgery and underwent reconstruction using a modular endoprosthetic replacement. Twenty surviving patients and the modular prosthesis were evaluated using the rating system adopted by the Musculoskeletal Tumour Society. Eighteen patients had resection of the distal femur and two had resection of the proximal tibia. The average follow up was 36.5 months (range 6-93). Overall the results were excellent in two patients, good in 16 and fair in two. The prosthesis was rated as excellent in 13, good in four, fair in two and poor in one. The complications encountered are discussed. The authors conclude that this prosthesis provides a satisfactory form of reconstruction following limb salvage surgery for tumours about the knee.

Adolescent↗

PubMed1980

A theory of modular evolution for bacteriophages.

The modular theory of virus evolution has clear experimental support among the temperate bacteriophages of the enteric bacteria. However, there is also similar genetic and DNA heteroduplex evidence for such evolution among other families of bacteriophages: the virulent bacteriophages of the enterics comprise several families: the T-even group, the T3-T7 group (which has many members among different species of bacteria, including bacteria as widely divergent as E. coli and Caulobacter crescentus. It nicely explains the diffusion of very similar homologous bacteriophages into hosts whose own DNAs have diverged very greatly from each other in nucleotide sequence. It also accounts for the rigorous maintenance of regulatory schemes while units of function (including regions coding for proteins) diverge more rapidly. It should also be noted that the considerations that make modular evolution seem advantageous for bacteriophages apply equally well to viruses of higher organisms. Furthermore, the kinds of heteroduplex similarity observed among animal viruses are reminiscent of what is found for bacteriophages. Viruses found in widely divergent hosts show much greater similarity than would be expected; quite possibly animal viruses also evolve as a population of interchangeable modules.

Bacteriophage lambda↗

PubMed1998

Plasposons: modular self-cloning minitransposon derivatives for rapid genetic analysis of gram-negative bacterial genomes.

A series of modular mini-transposon derivatives which permit the rapid cloning and mapping of the DNA flanking the minitransposon's site of insertion has been developed. The basic plasposon, named TnMod, consists of the Tn5 inverted repeats, a conditional origin of replication, rare restriction endonuclease multiple cloning sites, and exchangeable antibiotic resistance cassettes. The broad host range and low target DNA sequence specificity of the Tn5 transposase, in combination with the flexibility afforded by the modular arrangement of TnMod, result in a versatile tool for the mapping of insertional mutations and the rapid recovery of clones from gram-negative bacteria.

DNA Transposable Elements↗

PubMed1993

Efficient transcriptional activation of many simple modular promoters by simian virus 40 large T antigen.

Simian virus 40 (SV40) large T antigen is a multifunctional protein which plays central roles during both lytic and transforming infections by SV40. It is a potent transcriptional activator and increases expression from the SV40 late promoter and from several cellular promoters. To understand better the transcriptional activation activity of large T antigen, we examined its ability to transactivate a set of simple modular promoters containing one of four upstream activation sequences coupled with one of three different TATA box sequences originally constructed and studied by Taylor and Kingston (Mol. Cell. Biol. 10:165-175, 1990). Large T antigen activated transcription from all of these simple promoters. The identity of the TATA box was a more important determinant of the final level of gene expression than was the identity of the upstream activating sequence element. We also determined the ability of a set of mutant SV40 large T antigens to activate a subset of these promoters. Several mutant SV40 large T antigens which had reduced ability to activate the complex SV40 late and Rous sarcoma virus long terminal repeat promoters showed reduced transcriptional activation activity on all of the modular promoters tested. We used a set of promoter derivatives of the human U6 small nuclear RNA promoter containing different TATA boxes and found that wild-type large T antigen could activate transcription from all of them, although to widely different levels of expression.

Animals↗

PubMed1982

Construction of a modular dihydrofolate reductase cDNA gene: analysis of signals utilized for efficient expression.

Dihydrofolate reductase (DHFR) modular genes have been constructed with segments containing the adenovirus major late promoter, a 3' splice site from a variable region immunoglobulin gene, a DHFR cDNA, and portions of the simian virus 40 (SV40) genome. DNA-mediated transfer of these genes transformed Chinese hamster ovary DHFR- cells to the DHFR+ phenotype. Transformants contained one to several copies of the transfected DNA integrated into the host genome. Clones subjected to growth in increasing concentrations of methotrexate eventually gave rise to lines containing several hundred copies of the transforming DNA. Analysis of the DHFR mRNA produced in amplified lines indicated the following. (i) All clones utilize the adenovirus major late promoter for transcription initiation. (ii) A hybrid intron formed by the 5' splice site of the adenovirus major late leader and a 3' splice site from a variable-region immunoglobulin gene is properly excised. (iii) The mRNA is not efficiently polyadenylated at sequences in the 3' end of the DHFR cDNA but rather uses polyadenylation signals downstream from the DHFR cDNA. Three independent clones produce a DHFR mRNA containing SV40 or pBR322 and SV40 sequences, and the RNA is polyadenylated at the SV40 late polyadenylation site. Another clone has recombined into cellular DNA and apparently uses a cellular sequence for polyadenylation. Introduction of a segment containing the SV40 early polyadenylation signal into the 3' end of the DHFR cDNA gene generated a recombinant capable of transforming cells to the DHFR+ phenotype with at least a 10-fold increase in efficiency, demonstrating the necessity for an efficient polyadenylation signal. Attachment of a DNA segment containing the transcription enhancer (72-base pair repeat) of SV40 further increased the biological activity of the modular DHFR gene 50- to 100-fold.

Adenoviridae↗

PubMed1985

TU elements: a heterogeneous family of modularly structured eucaryotic transposons.

We describe here a family of foldback transposons found in the genome of the higher eucaryote, the sea urchin Strongylocentrotus purpuratus. Two major classes of TU elements have been identified by analysis of genomic DNA and TU element clones. One class consists of largely similar elements with long terminal inverted repeats (IVRs) containing outer and inner domains and sharing a common middle segment that can undergo deletions. Some of these elements contain insertions. The second class is highly heterogeneous, with many different middle segments nonhomologous to those of the first-class and variable-sized inverted repeats that contain only an outer domain. The middle and insertion segments of both classes carry sequences that also are found unassociated from the inverted repeats at many other genomic locations. We conclude that the TU elements are modular structures composed of inverted repeats plus other sequence domains that are themselves members of different families of dispersed repetitive sequences. Such modular elements may have a role in the dispersion and rearrangement of genomic DNA segments.

Animals↗