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PubMed2000

Role of SR protein modular domains in alternative splicing specificity in vivo.

The SR proteins constitute a family of nuclear phosphoproteins which are required for constitutive splicing and also influence alternative splicing regulation. They have a modular structure consisting of one or two RNA recognition motifs (RRMs) and a C-terminal domain, rich in arginine and serine residues. The functional role of the different domains of SR proteins in constitutive splicing activity has been extensively studied in vitro; however, their contribution to alternative splicing specificity in vivo has not been clearly established. We sought to address how the modular domains of SR proteins contribute to alternative splicing specificity. The activity of a series of chimeric proteins consisting of domain swaps between different SR proteins showed that splice site selection is determined by the nature of the RRMs and that RRM2 of SF2/ASF has a dominant role and can confer specificity to a heterologous protein. In contrast, the identity of the RS domain is not important, as the RS domains are functionally interchangeable. The contribution of the RRMs to alternative splicing specificity in vivo suggests that sequence-specific RNA binding by SR proteins is required for this activity.

Adenovirus E1A Proteins↗

PubMed1999

Evolution of bHLH transcription factors: modular evolution by domain shuffling?

Multidomain proteins usually contain several conserved and apparently independently evolved domains. As a result, classifications based on only a single small domain may obscure the true evolutionary relationships of the proteins. The current classification of basic helix-loop-helix (bHLH) domain-containing proteins is based on the conserved bHLH domain alone. Herein, we explore whether sequence homology and, therefore, evolutionary relationships can be detected among the flanking or non-bHLH components of the amino acid sequences of 122 bHLH proteins. These 122 proteins were the same proteins previously used to construct the existing classification of the bHLH-domain-containing proteins. Several possible scenarios are examined in order to explain the observed patterns of sequence divergence, including (1) monophyly, (2) convergent evolution, (3) addition of functional components to the bHLH domain, and (4) modular evolution with domain shuffling. Drawing on several lines of evidence, we suggest that modular evolution by domain shuffling may have played an important role in the evolution of this large group of transcriptional regulators.

DNA-Binding Proteins↗

PubMed1997

Modular bifurcation endoprosthesis for treatment of abdominal aortic aneurysms.

OBJECTIVE: The authors analyzed a single group's experience treating abdominal aortic aneurysms (AAAs) with a new self-expanding, modular, bifurcated device. SUMMARY BACKGROUND DATA: Successful exclusion of AAAs by prototype devices has led to several controlled clinical trials evaluating prostheses designed and manufactured specifically for this application. METHODS: Sixteen patients (15 males, 1 female) of American Society of Anesthesiologists grade 2 through 4 and average age of 72 years had AAAs (average 57-mm diameter) treated as part of a phase I Food and Drug Administration-approved trial. RESULTS: All patients were treated successfully with no surgical conversions. No endoleaks or aneurysm enlargement was noted either predischarge by contrast computed tomography or on follow-up at 1 month by duplex ultrasound examination. At 6 months, 12 of 13 patients who were observed for this interval had no endoleaks, whereas one patient (patient 3) showed a small area of extravasation that appeared to arise from the device in an area that was traumatized at the time of deployment. One procedure-related mortality (6%) occurred in a patient who died of septic complications secondary to a gangrenous gallbladder diagnosed 1 day after the procedure. There were no device-related mortalities. Complications included two iliac artery dissections, two groin wound infections, and two transient elevations of serum creatinine. Other significant variables including median procedure length (5 hours), intensive care unit stay (1 day), hospitalization postprocedure (4.5 days), and blood loss (1100 mL) all decreased as the study progressed. Blood replacement in all but three patients was accomplished by autotransfusion or banked-autologous blood replacement. At 6-month follow-up in 13 patients, the maximum diameter of the aneurysm decreased by an average of 5.6 mm (range, 0-15 mm), and the maximal cross-sectional area decreased an average of 20.3% (range, 0-72%). CONCLUSIONS: This study suggests that endovascular prosthesis exclusion of AAAs using a self-expanding modular device may be effective in many patients who are otherwise surgical candidates for repair if further clinical studies confirm these observations.

Aged↗

PubMed1994

Modular activation and suppression of neocortical activity in the monkey revealed by optical imaging.

To examine functional local connections in the primate neocortex, we examined changes in optical signal by intracortical microstimulation (ICMS), using a voltage-sensitive dye (RH795) in frontal and parietal cortical areas of the anesthetized monkey. ICMS increased the optical signal at the stimulated site, followed by increases and decreases in a modular fashion at regions that were from hundreds of micrometres to a few millimetres from the stimulated site. These changes lasted for 100-250 ms after the offset of ICMS. Further, this increase in the optical signal was accompanied by an increase in electrical activity in the neurones. These findings suggest the presence of excitatory and inhibitory modular connections within the neocortical areas. It is likely that some functional 'modules' are activated concurrently by excitatory loops, which suppress the activity of other modules.

Animals↗

PubMed1996

Modular tibial augmentations in total knee arthroplasty.

Proximal tibial bony deficiencies are not uncommon in primary and revision total knee arthroplasty. Modular tibial augmentations were introduced to address these deficiencies. Alterations in strain distribution as a result of medial wedge and block augmentations were evaluated for a modular total knee arthroplasty system in 6 fresh frozen anatomic specimen tibias. Full-field strain patterns were examined using photoelastic coating methods, and high strain regions were evaluated using strain gage rosette techniques. The total knee arthroplasty installations were tested in static physiologic axial and torsional load configurations. The relative effects of sequential wedge and block augmentations compared with the nonaugmented case were statistically analyzed. There were no overall statistical differences in the 3 treatments in terms of maximal (principal) strains. A secondary analysis that evaluated specific location and load pattern combinations established several minor statistical differences along with insights into the manner in which each construct loads the proximal tibia. Although metal wedge augmentation commonly is used, block augmentation seems to be an appropriate alternative from a strain distribution standpoint in cases in which the block geometry better approximates the bony defect.

Bone Diseases↗

PubMed1996

Cobalt chromium molybdenum metal combination for modular hip prostheses.

The development of a metal combination for modular hip systems was motivated by the following observations: (1) wear particles from polyethylene acetabular components can lead to a foreign body reaction and late aseptic loosening and (2) well designed all metal hip prostheses had very low wear rates, usually causing no osteolytic problems. The following challenges had to be met: (1) metal alloy with the maximum wear resistance; (2) the optimal clearance (difference in diameter) between 28-mm ball head and acetabular component; and (3) equipping modern, modular hip systems with metal combinations while maintaining compatibility with existing components. The realization of a metal combination consisted of the stable anchoring of a standard metal lining in a polyethylene insert that, combined, is intended to provide adequate load transfer and fit to either the bone cement bed or the titanium shell. The metal lining is manufactured from a carbide containing cobalt chromium molybdenum wrought alloy (Protasul-21WF). From 1988 to 1995, approximately 40,000 metal combinations (Metasul) were implanted. From these, 44 single components, with a maximum time in situ of 5.5 years, were retrieved and examined. The total linear wear rate averaged 2 to 5 micrometers per year per component after the initial conditioning phase. Under these conditions, particle induced late aseptic loosening is not to be expected.

Biomechanical Phenomena↗

PubMed2001

Modular, mobile-bearing hinge total knee arthroplasty.

Early reports of hinge total knee arthroplasty showed high rates of complications and implant failure. Third-generation modular, mobile-bearing, hinge knee arthroplasty systems have evolved to decrease the deleterious stresses that contributed to the failures of earlier designs. The combined series of Barrack et al and Jones et al documents midterm results using the S-ROM Hinge Knee System for patients with significant soft and hard tissue deficiencies not suitable for standard, less constrained, revision knee systems. The combined series included 30 knees with a mean followup of 49 months. Knee Society clinical scores improved from 52 to 134 points. There were no mechanical failures of the implants. The knee system used provides press-fit diaphyseal stems and metaphyseal filling and loading sleeves, all of which showed apposition and positive remodeling of bone at followup radiographic analysis. The excellent midterm results of this modular, mobile-bearing, linked knee system suggest the orthopaedic surgeon can display increasing confidence in the selection of such a knee system when confronted with catastrophic, salvage knee arthroplasty.

Arthroplasty, Replacement, Knee↗

PubMed1991

Modular indirect calorimeter suitable for long-term measurements in multipatient intensive care units.

OBJECTIVE: The construction of an indirect calorimeter capable of long-term automated sequential monitoring of multiple patients in adult and pediatric ICUs. DESIGN: A prototype system utilizing modular engineering principles, including central respiratory mass spectrometer; validation by organic solvent combustion and nitrogen dilution methods, and Tissot spirometer. SETTING: Surgical and pediatric ICUs in a tertiary care university hospital. RESULTS: When expired minute volume was measured over a range of 4 to 28 L in six intubated patients, expired minute volume measured by the prototype system demonstrated a correlation coefficient of .998 compared with simultaneous expired minute volume measured by a Tissot spirometer. Organic solvent combustion demonstrated a maximum error of 3.8% for oxygen consumption (VO2) and an average error of 1.73 +/- 1.25% (SEM). The maximum error for the respiratory quotient was 3.0%, with an average error of 1.75 +/- 1.07%. VO2 (predicted) vs. VO2 (measured) demonstrated a correlation coefficient of .997. Validation with the nitrogen dilution method over a range of FIO2 from 0.21 to 0.60 demonstrated a maximum error of 7.9%, with an average error of -1.72 +/- 1.1% (n = 51). CONCLUSIONS: Indirect calorimetry by means of a shared system for measurements in multiple patients in ICUs is feasible and cost effective utilizing modular principles and a centralized respiratory gas analyzer.

Adult↗

PubMedDate not supplied

Adapting to change: the advantage of modular clinic design.

Architects have applied modular design concepts for years. Projects benefiting most are those where a few room types are repeated often. Ambulatory care facilities are excellent candidates because this project type typically consists of a large number of rooms that can be standardized. The new Kaiser Permanente Santa Clara Medical Office Building illustrates the benefits and flexibility of modular design.

Ambulatory Care Facilities↗

PubMed1995

Total knee replacement including a modular distal femoral component in elderly patients with acute fracture or nonunion.

Distal femoral fracture or nonunion in elderly patients with osteopenic bone and coexisting gonarthrosis poses a difficult treatment challenge. Open reduction and internal fixation with or without the use of bone cement may not provide sufficient stabilization, requires a prolonged period of weightbearing restrictions, and does not address preexisting knee arthrosis. We report five patients, three with distal femoral nonunion, two with acute distal femoral fracture, and all with concomitant gonarthrosis treated with total knee replacement including a modular distal femoral component [distal femoral replacement (DFR)]. In this group of patients, modular DFR provided immediate pain relief and allowed early weightbearing and aggressive rehabilitation. We recommend this treatment modality in selected osteopenic elderly patients with difficult distal femoral reconstructive problems and coexisting gonarthrosis.

Aged↗

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↗

PubMed2004

The modular segmental kinematic rotating hinge for nonneoplastic limb salvage.

From January 1980 to July 1998, 25 patients (26 knees) were treated with an arthroplasty using a Modular Segmental Kinematic Rotating Hinge total knee prosthesis for nonneoplastic limb salvage. The indications included: nonunion of a periprosthetic femur fracture (11 knees), severe bone loss and ligamentous instability (eight knees), nonunion of a supracondylar femur fracture (four knees), acute periprosthetic fracture (one knee), fracture of a previous hinge (one knee), and prior resection arthroplasty (one knee). The average age of the patients was 72.3 years. Twenty-two arthroplasties were revisions. The average followup was 58.5 months. At the latest followup, knee extension averaged 2.4 degrees and flexion averaged 93.6 degrees. The Knee Society knee score improved from an average of 45.4 preoperatively to 75.5. Preoperatively, functional scores averaged 8.6 and improved to 25. Complications occurred in eight patients. The most common was deep infection (five patients). The use of the Modular Kinematic Rotating Hinge for nonneoplastic limb salvage represents a small proportion (0.14%) of all primary and revision knee arthroplasties done at our institution. The indications for the surgery are for a highly complex and small subset of patients. The patients in the current study gained significant improvement in overall range of motion, Knee Society knee scores, and functional scores when this prosthesis was used.

Aged↗

PubMed2004

Femoral fixation in the face of considerable bone loss: the use of modular stems.

Considerable femoral bone loss can be encountered in the multiply revised total hip arthroplasty patient. Deficient proximal bone requires either a bulk allograft or a femoral component that allows stable distal fixation. Extensively coated stems have shown excellent results for many revisions but have shown higher rates of failure among patients with femoral remodeling in retroversion, an enlarged endosteal diameter, or an ectatic canal. A modular tapered stem is an alternative in this subset of patients. A modular tapered implant provides axial and rotational stability through the use of distal splines, and the proximal body segments can allow independent adjustment of leg length, offset, and anteversion.

Aged↗

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↗

PubMed2006

Temperature-mediated transitions between isometry and allometry in a colonial, modular invertebrate.

The evolutionary success of animal design is strongly affected by scaling and virtually all metazoans are constrained by allometry. One body plan that appears to relax these constraints is a colonial modular (CM) design, in which modular iteration is hypothesized to support isometry and indeterminate colony size. In this study, growth rates of juvenile scleractinians (less than 40mm diameter) with a CM design were used to test this assertion using colony diameters recorded annually for a decade and scaling exponents (b) for growth calculated from double logarithmic plots of final versus initial diameters. For all juvenile corals, b differed significantly among years, with isometry (b=1) in 4 years, but positive allometry (b>1) in 5 years. The study years were characterized by differences in seawater temperature that were associated significantly with b for growth, with isometry in warm years but positive allometry in cool years. These results illustrate variable growth scaling in a CM taxon and suggest that the switch between scaling modes is mediated by temperature. For the corals studied, growth was not constrained by size, but this outcome was achieved through both isometry and positive allometry. Under cooler conditions, positive allometry may be beneficial as it represents a growth advantage that increases with size.

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↗