Biomedical subjects

M M Murray

Publications and source records attributed to M M Murray.

At least 19 recordsLinked to original sources

PubMed2006

The effect of thrombin on ACL fibroblast interactions with collagen hydrogels.

Premature loss of provisional scaffold formation has been identified as one of the factors responsible for poor healing of intraarticular tissues. To address this deficiency, substitute provisional scaffolds are being developed. The function of these scaffolds can be enhanced by the addition of specific extracellular matrix proteins. In this study, it was hypothesized that the addition of thrombin to a provisional scaffold material would result in increases in cell proliferation, collagen production, and cell migration within the scaffold. These three parameters are thought to be critical components of wound healing. Gels containing fibrin and collagen supplemented with either 0, 10.5, 21, or 42 U/mL of thrombin were placed in contact with explants of tissue from the anterior cruciate ligament. The addition of thrombin stimulated cell migration at low concentrations and impaired migration at higher concentrations, and had no significant effect on cell proliferation or collagen production. The use of all concentrations of thrombin resulted in mechanically weaker gels. Thus, the use of thrombin to optimize a collagen-platelet rich plasma (PRP) provisional scaffold must be done with caution, and use of high concentrations of thrombin (>42 IU/mL) should be avoided specifically in situations where gel strength or cell ingrowth is important. Use of low concentrations of thrombin (10.5 IU/mL) may be beneficial in applications where a faster set time and enhanced cell migration are desirable and the gel mechanical strength is of secondary importance.

Animals↗

PubMed2006

The central ACL defect as a model for failure of intra-articular healing.

Intra-articular soft tissues, such as the anterior cruciate ligament (ACL), fail to heal in contrast to the extra-articular medial collateral ligament (MCL), which undergoes classic healing. The goal of this study was to validate a model for failure of intra-articular healing that could be used in the future to test new repair strategies. We conducted a two-part experiment, the first part ex vivo, and the second in vivo. Our initial ex vivo experiments were used to determine the optimal width of the central defect in the canine ACL that would produce reproducible structural properties at time zero. The second experimental series used this optimal scalpel blade width to create a central defect in the canine ACL followed by measurement of structural properties in the ACL after either a 3- or 6-week in vivo healing period. A 3.5-mm beaver blade resulted in a maximum tolerated load of 56.8 +/- 4.7% (mean +/- SEM) of control at time zero. After the 3- and 6-week in vivo healing periods, the maximum load was 74.6 +/- 5.3 at 3 weeks and 64.9 +/- 3.8% at 6 weeks compared to control. Thus, biomechanical parameters tested at 6 weeks after creation of a defect showed no significant gains from defects tested immediately after the creation of injury. The centrally placed ACL defect in this canine model demonstrates failure to mechanically heal, which should prove suitable for future in vivo evaluation of the biomechanical and histological response to tissue engineering repair strategies for intra-articular soft tissues.

Animals↗

PubMed2001

The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N.

AQ4N is a bioreductive drug that can significantly enhance the anti-tumour effect of radiation and cyclophosphamide. The aim of this study was to examine the ability of AQ4N to potentiate the anti-tumour effect of cisplatin and to compare it to the chemopotentiation effect of tirapazamine. In the T50/80 murine tumour model, AQ4N (50-100 mg/kg) was administered 30 min, 2.5 or 6 h prior to cisplatin (4 mg/kg or 8 mg/kg); this produced an anti-tumour effect that was approximately 1.5 to 2 times greater than that achieved by a single 4 or 8 mg/kg dose of cisplatin. Tirapazamine (25 mg/kg) administered 2.5 h prior to cisplatin (4 mg/kg) resulted in a small increase in anti-tumour efficacy. AQ4N was also successful in enhancing the anti-tumour effect of cisplatin in the SCCVII and RIF-1 murine tumour models. This resulted in an increased cell kill of greater than 3 logs in both models; this was a greater cell kill than that observed for tirapazamine with cisplatin. Combination of cisplatin with AQ4N or tirapazamine resulted in no additional bone marrow toxicity compared to cisplatin administered alone. In conclusion, AQ4N has the potential to improve the clinical efficacy of cisplatin.

Animals↗

PubMed2001

Visual perceptual learning in human object recognition areas: a repetition priming study using high-density electrical mapping.

It is often the case that only partial or degraded views of an object are available to an observer, and yet in many of these cases, object recognition is accomplished with surprising ease. The perceptual filling-in or "closure" that makes this possible has been linked to a group of object recognition areas in the human brain, the lateral occipital (LO) complex, and has been shown to have a specific electrophysiological correlate, the N(cl) component of the event related potential. Perceptual closure presumably occurs because repeated and varied exposure to different classes of objects has caused the brain to undergo "perceptual learning," which promotes a robust mnemonic representation, accessible under partial information circumstances. The present study examined the impact of perceptual learning on closure-related brain processes. Fragmented pictures of common objects were presented, such that information content was incrementally increased until just enough information was present to permit closure and object recognition. Periodic repetition of a subset of these picture sequences was used to induce repetition priming due to perceptual learning. This priming has an electrophysiological signature that is putatively generated in the LO complex, but significantly precedes the electrophysiological correlate of closure. The temporal progression of priming- and closure-related activity in the LO complex supports the view that sensory processing entails multiple reentrant stages of activity within processing modules of the visual hierarchy. That the earliest priming-related activity occurs over LO complex, suggests that the sensory trace itself may reside in these object recognition areas.

Adult↗

PubMed2001

Visuo-spatial neural response interactions in early cortical processing during a simple reaction time task: a high-density electrical mapping study.

The timecourse and scalp topography of interactions between neural responses to stimuli in different visual quadrants, straddling either the vertical or horizontal meridian, were studied in 15 subjects. Visual evoked potentials (VEPs) were recorded from 64 electrodes during a simple reaction time (RT) task. VEPs to single stimuli displayed in different quadrants were summed ('sum') and compared to the VEP response from simultaneous stimulation of the same two quadrants ('pair'). These responses would be equivalent if the neural responses to the single stimuli were independent. Divergence between the 'pair' and 'sum' VEPs indicates a neural response interaction. In each visual field, interactions occurred within 72-86 ms post-stimulus over parieto-occipital brain regions. Independent of visual quadrant, RTs were faster for stimulus pairs than single stimuli. This replicates the redundant target effect (RTE) observed for bilateral stimulus pairs and generalizes the RTE to unilateral stimulus pairs. Using Miller's 'race' model inequality (Miller J. Divided attention: evidence for coactivation with redundant signals, Cognitive Psychology 1982;14:247-79), we found that probability summation could fully account for the RTE in each visual field. Although measurements from voltage waveforms replicated the observation of earlier peak P1 latencies for the 'pair' versus 'sum' comparison (Miniussi C, Girelli M, Marzi CA. Neural site of the redundant target effect: electrophysiological evidence. Journal of Cognitive Neuroscience 1998;10:216-30), this did not hold with measurements taken from second derivative (scalp current density) waveforms. Since interaction effects for bilateral stimulus pairs occurred within 86 ms and require interhemispheric transfer, transcallosal volleys must arrive within 86 ms, which is earlier than previously calculated. Interaction effects for bilateral conditions were delayed by approximately 10 ms versus unilateral conditions, consistent with current estimates of interhemispheric transmission time. Interaction effects place an upper limit on the time required for neuronal ensembles to combine inputs from different quadrants of visual space ( approximately 72 ms for unilateral and approximately 82 ms for bilateral conditions).

Adult↗

PubMed2001

The migration of cells from the ruptured human anterior cruciate ligament into collagen-glycosaminoglycan regeneration templates in vitro.

Guided tissue regeneration of the ruptured anterior cruciate ligament (ACL) offers the potential benefits of retaining the complex footprints of the ACL and the proprioceptive nerve fibers of the tissue. For this approach to be successful, ACL cells must retain the ability to migrate into an adjacent regeneration template, or scaffold, after ligament rupture. Ruptured ACLs were obtained from the knees of four men, ages 25-35, at the time of ACL reconstruction. Explants of ACL tissue were taken from three locations along the longitudinal axis of the remnant: the rupture site, the middle of the remnant, and far from the rupture site. These three areas have been found to be distinct histologically, with the region far from the rupture site having a histologic appearance similar to the intact ligament. Explants from each area were cultured in conventional tissue culture dishes (2-D culture) and on porous collagen-glycosaminoglycan (CG) scaffolds. Two-dimensional outgrowth was measured 3 times a week, and the 3-D explant/scaffold constructs were examined at 1, 2, 3 and 4 weeks to assess outgrowth of cells into the scaffold. The cell number density and expression of a-smooth muscle actin (SMA) were determined at each time point. The decrease in the diameter of the scaffolds and non-seeded controls were determined as a function of time in culture. The outgrowth of cells onto the tissue culture dishes was observed to begin as early as 3 days and as late as 21 days, with outgrowth first detected at an average of 6.8 +/- 2.0 days after explantation. In general, there was a larger area of outgrowth at the 2-week time point from explants with higher cell number density and higher blood vessel density. The 2-week area of outgrowth also correlated with the percentage of SMA-positive cells in the explant. In the experimental constructs with CG scaffolds, fibroblasts were noted to migrate from the human ACL explants into the templates at the earliest time point recorded (I week). The migration and proliferation of cells from the explants in the CG matrices resulted in an increase in the cell density in the scaffolds with time. There was a significant effect of the location from which the explant was taken on cell density in the scaffold, with a higher density of cells migrating from the explants from the rupture site of the ACL specimens. The percentage of cells staining positive for the SMA isoform varied from 0 to 50% of cells in the scaffold. Scaffolds co-cultured with explants showed a reduction in diameter that was significantly affected by time in culture and the location in the ACL from which the explant was taken. The percentage contraction attributed to the cells was 15% at 2 weeks, and increased to 27% for the injury-zone explant at 4 weeks. There was a significant correlation of the cell-mediated contraction of the matrices at 4 weeks with the cell density in the scaffolds, but not with the number of SMA-positive cells in the scaffolds. These data demonstrate that cells in the human ACL retain their ability to migrate into an adjacent CG scaffold in vitro, weeks after complete rupture. Moreover, the ACL-derived cells can express a contractile actin isoform and can contract a CG analog of extracellular matrix.

Actins↗

PubMed2001

Distribution of smooth muscle actin-containing cells in the human meniscus.

This is the first report of a contractile actin isoform, a-smooth muscle actin (SMA), in the cells of the human meniscus that lacked meniscal tears based on gross anatomical appearance. Approximately 25% of the cells in the tissue contained SMA by immunohistochemistry. Most of the SMA-positive cells were chondrocytic in morphology.

Actins↗

PubMed2001

The presence of smooth muscle actin in fibroblasts in the torn human rotator cuff.

The rotator cuff frequently sustains athletic and occupational injury, often resulting in chronic pain and disability. However, despite the high incidence of such shoulder problems, the pathophysiology of rotator cuff injury and healing has not yet been fully elucidated. The notable finding of this study was the presence of a contractile actin isoform, alpha-smooth muscle actin (SMA), in nonvascular cells in all of the seven torn human rotator cuff specimens evaluated immunohistochemically. Up to 95% of cells in any one region, and over 95% of elongated cells found in association with crimped collagen, contained SMA. Most of the cells staining positive for SMA in these sections had morphological features of the fibroblast, though a small number were chondrocyte-like. Treatment of cells growing out from human rotator cuff explants with TGF-beta1 significantly increased the amount of SMA evaluated by Western blot analysis. PDGF-BB and IFN-gamma had no effect on the cell content of SMA. This is the first documentation of the presence of SMA-positive cells in the human rotator cuff tendon. SMA has been found in a number of other healing connective tissues including skin, ligament, meniscus, cartilage, and other types of tendon. Of importance are previous findings that SMA-positive cells can contract a collagen-glycosaminoglycan analog of extracellular matrix in vitro. The results of the present study thus suggest that SMA-containing cells could contribute to the retraction of the torn ends of a ruptured rotator cuff and play an important role in healing.

Actins↗

PubMed2001

Attention-dependent suppression of distracter visual input can be cross-modally cued as indexed by anticipatory parieto-occipital alpha-band oscillations.

Recent studies show that in addition to enhancing neural processing for attentionally relevant stimuli, selective attention also operates by suppressing the processing of distracter stimuli. When subjects are pre-cued to selectively deploy attention during voluntary (endogenous) attentional tasks, these mechanisms can be set up in advance of actual stimulus processing. That is, the brain can be placed in a biased attentional state. Two recent cueing studies have provided evidence for the deployment of such biased attentional states [J.J. Foxe, G.V. Simpson, S.P. Ahlfors, Neuroreport 9 (1998) 3929-3933; M.S. Worden, J.J. Foxe, N. Wang, G.V. Simpson, J. Neurosci. 20:RC63 (2000) 1-6]. Specifically, these studies implicated oscillatory activity in the alpha frequency-band (8-14 Hz) as an anticipatory mechanism for suppressing distracter visual stimulation. The current study extends these findings by showing that this alpha-suppressive effect is also invoked by cross-modal cues. Auditory symbolic cues were used in an intermodal attention task, to direct subjects' attention to a subsequent task in either the visual or auditory modality. Cueing attention to the auditory features of the imminent task stimuli resulted in significantly higher parieto-occipital alpha amplitude in the period preceding onset of this stimulus than when attention was cued to the visual features. Topographic mapping suggests that this effect is generated in regions of the inferior parietal cortex, areas that have been repeatedly implicated in the engagement and maintenance of visual attention. Taken together, the results of this series of studies suggest that these parietal regions are capable of integrating sensory cues from multiple sensory modalities in order to program the subsequent deployment of visual attention.

Acoustic Stimulation↗

PubMed2000

Migration of cells from human anterior cruciate ligament explants into collagen-glycosaminoglycan scaffolds.

Regeneration of the human anterior cruciate ligament after complete rupture offers several theoretical advantages over reconstruction, including maintenance of the complex insertion sites and fan-shape of the ligament and preservation of remaining proprioceptive fibers within the ligament substance. Well vascularized connective tissues, such as dermis, heal as a result of migration of fibroblasts into a provisional scaffold, the fibrin clot. Wound closure is subsequently facilitated by a contractile cell phenotype. This study was designed to determine if fibroblasts intrinsic to the human anterior cruciate ligament were capable of migrating from their native extracellular matrix onto an adjacent provisional scaffold in vitro. Another objective was to determine whether any of the cells that successfully migrated into the scaffold expressed the contractile actin isoform, alpha-smooth muscle actin, associated with wound contraction in other tissues. The results demonstrated that the cells intrinsic to the human anterior cruciate ligament were able to migrate into a collagen-glycosaminoglycan scaffold, bridging a gap between transected fascicles in vitro. As a result of this cell migration and proliferation, areas in the scaffold contained cell number densities similar to those seen in the human anterior cruciate ligament in vivo. No extracellular matrix or tissue formation was seen in the gap between directly apposed transected ends of the anterior cruciate ligament explants cultured without an interposed collagen-glycosaminoglycan scaffold. The fascicle-collagen-glycosaminoglycan-fascicle constructs and the fascicle-fascicle explants displayed minimal adherence after 6 weeks in culture. Any disruption in the contact area between explant and scaffold, even as small a gap as 50 microm, prevented cell migration from the explant to the collagen-glycosaminoglycan scaffold at the area of loss of contact. All cells that migrated into the scaffold at early time periods expressed the alpha-smooth muscle actin isoform. These results demonstrate that cells that migrate into and proliferate within the collagen-glycosaminoglycan matrix have contractile potential as reflected in their expression of the alpha-smooth muscle actin isoform. The role of these contractile cells in the healing process warrants further investigation. Moreover, this study demonstrates the potential of cells intrinsic to the human anterior cruciate ligament to migrate into collagen-glycosaminoglycan scaffolds that may ultimately be investigated as implants to facilitate ligament healing and regeneration.

Actins↗

PubMed2000

Multisensory auditory-somatosensory interactions in early cortical processing revealed by high-density electrical mapping.

We investigated the time-course and scalp topography of multisensory interactions between simultaneous auditory and somatosensory stimulation in humans. Event-related potentials (ERPs) were recorded from 64 scalp electrodes while subjects were presented with auditory-alone stimulation (1000-Hz tones), somatosensory-alone stimulation (median nerve electrical pulses), and simultaneous auditory-somatosensory (AS) combined stimulation. Interaction effects were assessed by comparing the responses to combined stimulation with the algebraic sum of responses to the constituent auditory and somatosensory stimuli when they were presented alone. Spatiotemporal analysis of ERPs and scalp current density (SCD) topographies revealed AS interaction over the central/postcentral scalp which onset at approximately 50 ms post-stimulus presentation. Both the topography and timing of these interactions are consistent with multisensory integration early in the cortical processing hierarchy, in brain regions traditionally held to be unisensory.

Acoustic Stimulation↗

PubMed2000

Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine.

The ability of the bioreductive drugs AQ4N and tirapazamine to enhance the anti-tumour effect of cyclophosphamide was assessed in three murine tumour models. In male BDF mice implanted with the T50/80 mammary carcinoma, AQ4N (50-150 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 200 mg kg 1 dose of cyclophosphamide. Tirapazamine (25 mg kg(-1)) in combination with cyclophosphamide (100 mg kg(-1)) produced an effect equivalent to a single 150 mg kg(-1) dose of cyclophosphamide. In C3H mice implanted with the SCCVII or RIF-1 tumours, enhancement of tumour cell killing was found with both drugs in combination with cyclophosphamide (50-200 mg kg(-1)); AQ4N (50-200 mg kg(-1)) produced a more effective combination than tirapazamine (12.5-50 mg kg(-1)). Unlike tirapazamine, which showed a significant increase in toxicity to bone marrow cells, the combination of AQ4N (100 mg kg(-1)) 6 h prior to cyclophosphamide (100 mg k(-1)) resulted in no additional toxicity towards bone marrow cells compared to that caused by cyclophosphamide alone. In conclusion, AQ4N gave a superior anti-tumour effect compared to tirapazamine when administered with a single dose of cyclophosphamide (100 mg kg(-1)).

Animals↗

PubMed2000

Combinations of variations in multiple genes are associated with hypertension.

The genetic analysis of hypertension has revealed complex and inconsistent results, making it difficult to draw clear conclusions regarding the impact of specific genes on blood pressure regulation in diverse human populations. Some of the confusion from previous studies is probably due to undetected gene-gene interactions. Instead of focusing on the effects of single genes on hypertension, we examined the effects of interactions of alleles at 4 candidate loci. Three of the loci are in the renin-angiotensin-system, angiotensinogen, ACE, and angiotensin II type 1 receptor, and they have been associated with hypertension in at least 1 previous study. The fourth locus studied is a previously undescribed locus, named FJ. In total, 7 polymorphic sites at these loci were analyzed for their association with hypertension in 51 normotensive and 126 hypertensive age-matched individuals. There were no significant differences between the 2 phenotypic classes with respect to either allele or genotype frequencies. However, when we tested for nonallelic associations (linkage disequilibrium), we found that of the 120 multilocus comparisons, 16 deviated significantly from random in the hypertensive class, but there were no significant deviations in the normotensive group. These findings suggest that genetic interactions between multiple loci rather than variants of a single gene underlie the genetic basis of hypertension in our study subjects. We hypothesize that such interactions may account for the inconsistent findings in previous studies because, unlike our study, prior studies almost always examined single-locus effects and did not consider the effects of variation at other potentially interacting loci.

Adolescent↗

PubMed2000

Activation timecourse of ventral visual stream object-recognition areas: high density electrical mapping of perceptual closure processes.

Object recognition is achieved even in circumstances when only partial information is available to the observer. Perceptual closure processes are essential in enabling such recognitions to occur. We presented successively less fragmented images while recording high-density event-related potentials (ERPs), which permitted us to monitor brain activity during the perceptual closure processes leading up to object recognition. We reveal a bilateral ERP component (N(cl)) that tracks these processes (onsets approximately 230 msec, maximal at approximately 290 msec). Scalp-current density mapping of the N(cl) revealed bilateral occipito-temporal scalp foci, which are consistent with generators in the human ventral visual stream, and specifically the lateral-occipital or LO complex as defined by hemodynamic studies of object recognition.

Adolescent↗

PubMed2000

Histological changes in the human anterior cruciate ligament after rupture.

BACKGROUND: Four phases in the response to injury of the ruptured human anterior cruciate ligament are observed histologically; these include an inflammatory phase, an epiligamentous repair phase, a proliferative phase, and a remodeling phase. One objective of this study was to describe the histological changes that occur in the ruptured human anterior cruciate ligament during these phases. Myofibroblast-like cells that contain alpha-smooth muscle actin are present in the midsubstance of the intact human anterior cruciate ligament. A second objective of this study was to determine whether an increased number of myofibroblast-like cells is found in the midsubstance of the ruptured human anterior cruciate ligament because it was thought that those cells might be responsible in part for the retraction of the ruptured anterior cruciate ligament. In the early phase of this study, it was found that the number of myofibroblast-like cells in the midsubstance of the ruptured anterior cruciate ligament was actually decreased, and this hypothesis was abandoned. During the epiligamentous repair phase, synovial tissue was formed that covered the ends of the ruptured anterior cruciate ligament. Most of the synovial lining cells were myofibroblast-like cells that contained alpha-smooth muscle actin. The primary objective of this study was to determine the location and the characteristics of the alpha-smooth muscle actin-containing myofibroblast-like cells that appear in the human anterior cruciate ligament following rupture. METHODS: Twenty-three ruptured and ten intact human anterior cruciate ligaments were evaluated for cellularity, nuclear morphology, blood vessel density, and percentage of cells containing a contractile actin isoform, alpha-smooth muscle actin. The histological features of the synovial and epiligamentous tissues were also described. RESULTS: At no time after rupture was there evidence of tissue-bridging between the femoral and tibial remnants of the anterior cruciate ligament. The ruptured ligaments demonstrated a time-dependent histological response, which consisted of inflammatory cell infiltration up to three weeks, gradual epiligamentous repair and resynovialization between three and eight weeks, and neovascularization and an increase in cell number density between eight and twenty weeks. Compared with the intact ligaments, there was a decrease in the percentage of myofibroblast-like cells containing alpha-smooth muscle actin within the remnant of the ligament. However, many of the epiligamentous and synovial cells encapsulating the remnants contained alpha-smooth muscle actin. CONCLUSIONS: After rupture, the human anterior cruciate ligament undergoes four histological phases, consisting of inflammation, epiligamentous regeneration, proliferation, and remodeling. The response to injury is similar to that reported in other dense connective tissues, with three exceptions: formation of an alpha-smooth muscle actin-expressing synovial cell layer on the surface of the ruptured ends, the lack of any tissue bridging the rupture site, and the presence of an epiligamentous reparative phase that lasts eight to twelve weeks. Other characteristics reported in healing dense connective tissue, such as fibroblast proliferation, expression of alpha-smooth muscle actin, and revascularization, also occur in the ruptured human anterior cruciate ligament. CLINICAL RELEVANCE: Unlike extra-articular ligaments that heal after injury, the human intra-articular anterior cruciate ligament forms a layer of synovial tissue over the ruptured surface, which may impede repair of the ligament. Moreover, a large number of cells in this synovial layer and in the epiligamentous tissue express the gene for a contractile actin isoform, alpha-smooth muscle actin, thus differentiating into myofibroblasts. These events may play a role in the retraction and lack of healing of the ruptured anterior cruciate ligament.

Actins↗

PubMed1999

Fibroblast distribution in the anteromedial bundle of the human anterior cruciate ligament: the presence of alpha-smooth muscle actin-positive cells.

The anterior cruciate ligament is a complex tissue composed of structural proteins, proteoglycans, and cells. The histology of the human anterior cruciate ligament is characterized by the specific distribution and density of the fibroblast phenotype as well as by the unique organization of the structural proteins. A notable finding of this study was the identification of three histologically different zones along the anteromedial bundle as it coursed from the femoral to the tibial attachment. Two of the zones, the fusiform and ovoid, were located in the proximal one-quarter of the bundle; the third zone, the spheroid, occupied the distal three quarters of the bundle fascicles. The fusiform cell zone was characterized by a high number density of longitudinally oriented cells with a fusiform-shaped nucleus, longitudinal blood vessels, and high crimp length. The cytoplasm of the cells in this zone appeared to be intimately attached to the extracellular collagen and followed the crimp waveform of the fibers. Fusiform cells were noted to stain positively for the alpha-smooth muscle actin isoform in this region, particularly at areas of crimp disruption. The ovoid cell zone was characterized by a high number density of cells with an ovoid-shaped nucleus, longitudinal vessels, and a high crimp length. In this zone as well, the cytoplasm of the cells appeared to follow the waveform of the adjacent collagen. Ovoid cells were noted to stain positively for the alpha-smooth muscle actin isoform in this region. The spheroid cell zone was characterized by a low density of spheroid cells, few blood vessels, and short crimp length. Cells were noted within and among fascicles, as well as within lacunae. In selected areas, as many as 50% of the cells in this region stained positively for the alpha-smooth muscle actin isoform. This is also the first report of cells expressing the alpha-smooth muscle actin isoform in the intact human anterior cruciate ligament. This specific type of contractile actin, initially identified only in smooth-muscle cells, pericytes, and myofibroblasts, was seen in cells with various morphologies and predominantly in cells located at areas of crimp disruption. Further work is necessary to elucidate the role of the various fibroblast phenotypes in the maintenance of the human anterior cruciate ligament.

Actins↗

PubMed1995

Distal tibial mononeuropathy in diabetic and nondiabetic rats reared on wire cages: an experimental entrapment neuropathy.

Using electrophysiological recordings, we studied a distal tibial mononeuropathy that involves the hind foot of rats reared in cages with wire grid flooring. In an initial set of experiments, serial sciatic-tibial motor conduction recordings were made in smaller or larger rats reared in cages with wire grid or sawdust flooring. Electrophysiological features of the neuropathy were loss in the amplitude of the distal tibial nerve M potential recorded over hind limb foot muscles, temporal dispersion of the potential, often into multiple peaks, and a prolonged distal latency of the response. The changes in M amplitude were more apparent in larger rats with a greater body weight. In a second series of experiments we studied sciatic-tibial conduction over 16 weeks in nondiabetic rats and rats rendered diabetic with streptozotocin raised and wire grid or plastic flooring. Tibial mononeuropathy developed in both wire grid-reared groups, but there was evidence that it appeared earlier in diabetic rats. Electrophysiological changes of distal mononeuropathy also obscured the expected slowing of sciatic-tibial motor conduction velocity from diabetics. Tibial mononeuropathy in rats reared on wire grid flooring may be a useful animal model of human entrapment neuropathy but its presence can confound studies of experimental neuropathy. Rats used in studies of experimental neuropathy should be housed in plastic cages with sawdust or shavings flooring.

Analysis of Variance↗

PubMed1995

Comparison of 1% and 2.5% selenium sulfide in the treatment of tinea capitis.

OBJECTIVE: To determine whether an over-the-counter shampoo containing 1% selenium sulfide would have sporicidal activity equal to that of a 2.5% selenium sulfide prescription lotion in the adjunctive treatment of tinea capitis infection. DESIGN: Prospective randomized nonblinded clinical trial. SETTING: Outpatient clinics and emergency department of a children's hospital. PATIENTS: Fifty-four patients between the ages of 1 and 15 years with culture-proved tinea capitis infection caused by Trichophyton tonsurans enrolled during a 14-month period. METHODS: Patients were randomized to receive 2.5% selenium sulfide lotion, 1% selenium sulfide shampoo, or a bland, nonmedicated shampoo with which they were instructed to shampoo twice weekly. All received 15 mg/kg per day of griseofulvin. Dermatophyte cultures of the affected area of each patient's scalp were obtained on enrollment and every 2 weeks until a negative culture was obtained from a previously infected area. RESULTS: Survival data analysis demonstrated that both the 2.5% selenium sulfide and 1% selenium sulfide preparations were superior to the nonmedicated control shampoo in terms of the time required to eliminate shedding of viable spores. When compared with each other, there was no difference between the 2.5% selenium sulfide and 1% selenium sulfide preparations in time required to produce a negative culture. CONCLUSION: Commercially available 1% selenium sulfide shampoo is an equally effective yet less expensive alternative sporicidal therapy in the adjunctive treatment of tinea capitis infection.

Adolescent↗