Type IID Research Articles

Differentiation and fiber type-specific activity of a muscle creatine kinase intronic enhancer

BackgroundHundreds of genes, including muscle creatine kinase (MCK), are differentially expressed in fast- and slow-twitch muscle fibers, but the fiber type-specific regulatory mechanisms are not well understood.ResultsModulatory region 1 (MR1) is a 1-kb regulatory region within MCK intron 1 that is highly active in terminally differentiating skeletal myocytes in vitro. A MCK small intronic enhancer (MCK-SIE) containing a paired E-box/myocyte enhancer factor 2 (MEF2) regulatory motif resides within MR1. The SIE's transcriptional activity equals that of the extensively characterized 206-bp MCK 5'-enhancer, but the MCK-SIE is flanked by regions that can repress its activity via the individual and combined effects of about 15 different but highly conserved 9- to 24-bp sequences. ChIP and ChIP-Seq analyses indicate that the SIE and the MCK 5'-enhancer are occupied by MyoD, myogenin and MEF2. Many other E-boxes located within or immediately adjacent to intron 1 are not occupied by MyoD or myogenin. Transgenic analysis of a 6.5-kb MCK genomic fragment containing the 5'-enhancer and proximal promoter plus the 3.2-kb intron 1, with and without MR1, indicates that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers (types I and IIa, respectively), but is not required for expression in fast-twitch muscle fibers (types IIb and IId).ConclusionsIn this study, we discovered that MR1 is critical for MCK expression in slow- and intermediate-twitch muscle fibers and that MR1's positive transcriptional activity depends on a paired E-box MEF2 site motif within a SIE. This is the first study to delineate the DNA controls for MCK expression in different skeletal muscle fiber types.

A Fragment-Specific Approach to Type IID Monteggia Elbow Fracture–Dislocations

To describe the pattern of injury, surgical technique, and outcomes of Monteggia Type IID fracture dislocations. Retrospective review of prospectively collected clinical and radiographic patient data in an orthopaedic trauma database. Level I university-based trauma center. All patients with Monteggia Type IID fracture-dislocations admitted from January 2000 to July 2005. Review of patient demographics, fracture pattern, method of fixation, complications, additional surgical procedures, and clinical and radiographic outcome measures. Clinical outcomes: elbow range of motion, complications. Radiographic outcomes: characteristic fracture fragments, quality of fracture reduction, healing time, degenerative changes, and heterotopic ossification. Sixteen patients were included in the study. All fractures united. There were six complications in six patients, including three contractures with associated heterotopic ossification, one pronator syndrome and late radial nerve palsy, one radial head collapse, and one with prominent hardware. Monteggia IID fracture-dislocations are complex injuries with typical specific fracture fragments. Anatomic fixation of all injury components and avoidance of complications where possible can lead to a good outcome in these challenging injuries.

Whirlin Replacement Restores the Formation of the USH2 Protein Complex in Whirlin Knockout Photoreceptors

Whirlin is the causative gene for Usher syndrome type IID (USH2D), a condition manifested as both retinitis pigmentosa and congenital deafness. Mutations in this gene cause disruption of the USH2 protein complex composed of USH2A and VLGR1 at the periciliary membrane complex (PMC) in photoreceptors. In this study, the adeno-associated virus (AAV)-mediated whirlin replacement was evaluated as a treatment option. Murine whirlin cDNA driven by the human rhodopsin kinase promoter (hRK) was packaged as an AAV2/5 vector and delivered into the whirlin knockout retina through subretinal injection. The efficiency, efficacy, and safety of this treatment were examined using immunofluorescent staining, confocal imaging, immunoelectron microscopy, Western blot analysis, histologic analysis, and electroretinogram. The AAV-mediated whirlin expression started at two weeks, reached its maximum level at 10 weeks, and lasted up to six months post injection. The transgenic whirlin product had a molecular size and an expression level comparable to the wild-type. It was distributed at the PMC in both rod and cone photoreceptors from the central to peripheral retina. Importantly, the transgenic whirlin restored the cellular localization and expression level of both USH2A and VLGR1 and did not cause defects in the retinal histology and function in the whirlin knockout mouse. Whirlin transgene recruits USH2A and VLGR1 to the PMC and is sufficient for the formation of the USH2 protein complex in photoreceptors. The combined hRK and AAV gene delivery system could be an effective gene therapy approach to treat retinal degeneration in USH2D patients.

Co‐transcriptional regulation during chondrogenesis

Alternative splicing of precursor mRNA (pre-mRNA) is the major mechanism that generates diversity of protein-coding transcripts in the cell. One of the most important pre-mRNA alternative splicing events in cartilage biology involves the type II collagen gene (COL2A1). Chondroprogenitor cells synthesize exon 2-containing transcripts (type IIA and IID isoforms) while differentiated chondrocytes predominantly synthesize COL2A1 transcripts devoid of exon 2 (type IIB). We have identified another COL2A1 transcript (type IIC) generated by an alternative 5′ splice site within exon 2. In vitro studies have shown that production of the type IIC isoform is required to regulate levels of the other COL2A1 protein-coding transcripts. We are currently generating knock-in transgenic mice with specific mutations in exon 2 splice sites to directly address the role of Col2a1 isoforms in vivo during skeletogenesis. Utilizing a novel real time PCR-based method, absolute levels of the four COL2A1 isoforms in mesenchymal stem cells (MSCs) at various time-points during TGFβ3-induced differentiation was determined. Of note, the ratio of IIA/IID:IIB transcripts varied between experiments, reflecting donor-to-donor variability of MSCs. Also, when MSCs were cultured in the presence of poly(ethylene glycol) microspheres, the ratio of IIA/IID:IIB isoforms was higher compared to MSCs cultured without microspheres. This suggests that cells may respond to a biomaterial environment by synthesizing an immature collagen matrix; these findings are particularly relevant to the field of cartilage tissue engineering.

Human skeletal muscle: transition between fast and slow fibre types

Human skeletal muscles consist of different fibre types: slow fibres (slow twitch or type I) containing the myosin heavy chain isoform (MHC)-I and fast fibres (fast twitch or type II) containing MHC-IIa (type IIA) or MHC-IId (type IID). The following order of decreasing kinetics is known: type IID > type IIA >> type I. This order is especially based on the kinetics of stretch activation, which is the most discriminative property among fibre types. In this study we tested if hybrid fibres containing both MHC-IIa and MHC-I (type C fibres) provide a transition in kinetics between fast (type IIA) and slow fibres (type I). Our data of stretch activation kinetics suggest that type C fibres, with different ratios of MHC-IIa and MHC-I, do not provide a continuous transition. Instead, a specialized group of slow fibres, which we called "transition fibres", seems to provide a transition. Apart of their kinetics of stretch activation, which is most close to that of type IIA, the transition fibres are characterized by large cross-sectional areas and low maximal tensions. The molecular cause for the mechanical properties of the transition fibres is unknown. It is possible that the transition fibres contain an unknown slow MHC isoform, which cannot be separated by biochemical methods. Alternatively, or in addition, isoforms of myofibrillar proteins, other than MHC, and posttranslational modifications of myofibrillar proteins could play a role regarding the characteristics of the transition fibres.

Characterization of Fiber Types in Different Muscles of the Hindlimb in Female Weanling and Adult Wistar Rats

We analyzed lesser diameter and distribution of fiber types in different skeletal muscles from female Wistar rats using a histoenzymology Myofibrillar Adenosine Tri-phosphatase (mATPase) method. Fragments from muscles were frozen and processed by mATPase in different pH. Adult and weanling rat soleus muscles presented a predominance of type I fibers and larger fiber diameters. In the plantar muscle in adult rats, the type IIB fibers demonstrated greater lesser diameter while in the weanling animals, types I and IIB fibers were larger. The plantar muscle of animals of both ages was composed predominantly of the type IID fibers. The type IID fibers were observed in similar amounts in the lateral gastrocnemius and the medial gastrocnemius muscles. Type IIB fibers showed predominance and presented higher size in comparison with other types in the EDL muscle. The present study shows that data on fiber type distribution and fiber lesser diameter obtained in adult animals cannot always be applied to weanling animals of the same species. Using the mATPase, despite the difficult handling, is an important tool to determine the different characteristics of the specific fibers in the skeletal muscle tissue.

Structural and functional analyses of PpENA1 provide insights into cation binding by type IID P-type ATPases in lower plants and fungi

PpENA1 is a membrane-spanning transporter from the moss Physcomitrella patens, and is the first type IID P-type ATPase to be reported in the plant kingdom. In Physcomitrella, PpENA1 is essential for normal growth under moderate salt stress, while in yeast, type IID ATPases provide a vital efflux mechanism for cells under high salt conditions by selectively transporting Na+ or K+ across the plasma membrane. To investigate the structural basis for cation-binding within the type IID ATPase subfamily, we used homology modeling to identify a highly conserved cation-binding pocket between membrane helix (MH) 4 and MH 6 of the membrane-spanning pore of PpENA1. Mutation of specific charged and polar residues on MHs 4–6 resulted in a decrease or loss of protein activity as measured by complementation assays in yeast. The E298S mutation on MH 4 of PpENA1 had the most significant effect on activity despite the presence of a serine at this position in fungal type IID ATPases. Activity was partially restored in an inactivated PpENA1 mutant by the insertion of two additional serine residues on MH 4 and one on MH 6 based on the presence of these residues in fungal type IID ATPases. Our results suggest that the residues responsible for cation-binding in PpENA1 are distinct from those in fungal type IID ATPases, and that a fungal-type cation binding site can be successfully engineered into the moss protein.

Fiber Type Composition of the Sternomastoid and Diaphragm Muscles of Dystrophin‐Deficient mdx Mice

The muscle fiber phenotype is mainly determined by motoneuron innervation and changes in neuromuscular interaction alter the muscle fiber type. In dystrophin-deficient mdx mice, changes in the molecular assembly of the neuromuscular junction and in nerve terminal sprouting occur in the sternomastoid (STN) muscle during early stages of the disease. In this study, we were interested to see whether early changes in neuromuscular assembly are correlated with alterations in fiber type in dystrophic STN at 2 months of age. A predominance of hybrid fast myofibers (about 52% type IIDB) was observed in control (C57Bl/10) STN. In mdx muscle, the lack of dystrophin did not change this profile (about 54% hybrid type IIDB). Pure fast type IID fibers predominated in normal and dystrophic diaphragm (DIA; about 39% in control and 30% in mdx muscle) and a population of slow Type I fibers was also present (about 10% in control and 13% in mdx muscle). In conclusion, early changes in neuromuscular assembly do not affect the fiber type composition of dystrophic STN. In contrast to the pure fast fibers of the more affected DIA, the hybrid phenotype of the STN may permit dynamic adaptations during progression of the disease.

Popliteal artery branching patterns detected by digital substraction angiography

To describe the popliteal and distal branching patterns detected by digital subtraction angiography. The popliteal branching patterns were analyzed in 535 extremities (270 right, 265 left). Of these, 226 limbs were evaluated bilaterally, while 83 were evaluated unilaterally. The branching patterns were classified according to the level of branching and the presence of hypoplasia or aplasia of the distal branches. Four hundred and seventy-two (88.1%) limbs had a normal level of popliteal artery branching. Type IA was the most frequently encountered pattern. High division of the popliteal artery was seen in 30 (5.6%) limbs. Type IIA was the most frequently encountered pattern among these limbs. Type IIC was not seen. We encountered a new pattern characterized by high division of the peroneal artery with a trifurcation pattern and an anterior tibial artery with a proximal medial course and a distal lateral course. We called this pattern Type IID. Thirty-three (6.1%) limbs exhibited hypoplasia/aplasia of the distal branches. Type IIIA was the most frequently encountered pattern among these limbs. Variations that occur in nearly 10% of patients should be understood because they may affect the choice of management strategy.

Congenital tibial dysplasia (congenital pseudoarthrosis of the tibia): an atypical variation

Purpose: The purpose of the study was to identify those characteristics of congenital tibial dysplasia (CTD) that portend the worst prognosis, including the probable failure of all surgical attempts to achieve union. Clear identification/ classification of this select population of cases could add earlier consideration of relevant treatment options. Method: While several classification systems for CTD exist, the Crawford classification was used to review the literature and our hospital cases (6) to examine the relationship between case characteristics, treatment, and outcome. Results: An atypical variation of Crawford’s type IIC was identified, herein referred to as type IID, that was characterized by early onset, frank pseudoarthrosis, and deformity of the distal-one third of the tibia and fibula. As well, these patients underwent failed multiple surgeries and numerous type treatments over time without good functional outcome and with prolonged physical difficulties. Conclusion: The cases that fall into this newly defined category (IID) of the Crawford classification for CTD are best treated with early amputation rather than repeated attempts to gain union. Significance: Amputation for patients with congenital tibial dysplasia (congenital pseudoarthrosis of the tibia) that are identified as type IID cases and carry the characteristics for a bad prognosis, provides better functional results than repeated surgeries, even when union is achieved. The family should be warned from the beginning that a stable union is unlikely in these cases. Amputation should be offered as a primary or an early option to the family with full disclosure of the long-term advantages and disadvantages of all therapeutic paths.

Effects of 14 days of microgravity on fast hindlimb and diaphragm muscles of the rat

The purpose of the present study was to determine the effects of 14 days of microgravity on specific rat fast-twitch muscles, and to compare these data with previous data from rat fast-twitch muscles exposed to microgravity for 10 days (Kraemer et al. 2000). Hindlimb muscles containing predominately fast fibers [extensor digitorum longus (EDL), superficial "white" (GSW) and deep "red" (GDR) gastrocnemius] and the diaphragm (DIA) were removed from flight and ground-based control animals and analyzed for: muscle mass, fiber type distribution, cross-sectional area, and myosin heavy chain (MHC) isoform content. Gravitational unloading for 14 days caused significant decreases in muscle mass (8-9%) and cross-sectional area of almost all fiber types (10-35%) from both EDL and gastrocnemius muscles. However, microgravity had little effect on fiber type composition in these muscles with significant changes occurring only in the EDL type IID fiber population (9.5% decrease). Similarly, relative MHC isoform content was only slightly altered by exposure to microgravity (increased content of MHCIIa in flight EDL). No changes in area, fiber type percentages, or MHC isoform content were detected in the DIA following the 14-day spaceflight. Similar to data gathered following a 10-day spaceflight (Kraemer et al. 2000), the 14-day flight did not appear to cause significant slow-to-fast (I --> IIA) or fast-to-faster (IIA --> IID --> IIB) transformations in hindlimb muscles containing predominantly fast-twitch fibers. However, the longer period of gravitational unloading did result in additional loss in muscle fiber cross-sectional area with involvement of more major fiber types.

Distinctive nicotinic acetylcholine receptor functional phenotypes of rat ventral tegmental area dopaminergic neurons

Dopaminergic (DAergic) neuronal activity in the ventral tegmental area (VTA) is thought to contribute generally to pleasure, reward, and drug reinforcement and has been implicated in nicotine dependence. nAChRs expressed in the VTA exhibit diverse subunit compositions, but the functional and pharmacological properties are largely unknown. Here, using patch-clamp recordings in single DAergic neurons freshly dissociated from rat VTA, we clarified three functional subtypes of nAChRs (termed ID, IID and IIID receptors) based on whole-cell current kinetics and pharmacology. Kinetic analysis demonstrated that comparing to ID, IID receptor-mediated current had faster activation and decay constant and IIID receptor-mediated current had larger current density. Pharmacologically, ID receptor-mediated current was sensitive to the alpha4beta2-nAChR agonist RJR-2403 and antagonist dihydro-beta-erythroidine (DHbetaE); IID receptor-mediated current was sensitive to the selective alpha7-nAChR agonist choline and antagonist methyllycaconitine (MLA); while IIID receptor-mediated current was sensitive to the beta4-containing nAChR agonist cytisine and antagonist mecamylamine (MEC). The agonist concentration-response relationships demonstrated that IID receptor-mediated current exhibited the highest EC(50) value compared to ID and IIID receptors, suggesting a relatively low agonist affinity of type IID receptors. These results suggest that the type ID, IID and IIID nAChR-mediated currents are predominately mediated by activation of alpha4beta2-nAChR, alpha7-nAChR and a novel nAChR subtype(s), respectively. Collectively, these findings indicate that the VTA DAergic neurons express diversity and multiplicity of functional nAChR subtypes. Interestingly, each DAergic neuron predominantly expresses only one particularly functional nAChR subtype, which may have distinct but important roles in regulation of VTA DA neuronal function, DA transmission and nicotine dependence.

Does the gestation age of newborn babies influence the ultrasonic assessment of hip condition?

Ultrasound represents a method of examination of hips of newborn babies capable of defining hip condition and distinguishing stable and unstable hips based on morphological elements. It is accepted in a large number of countries as a method of examination of high risk newborns, or as a method of systematic screening. The objective of this study was to investigate correlation between ultrasonically estimated hip maturity and respective gestation maturity both in premature and term-born babies, and to investigate the influence of different delivery types on hips condition. In our study 2045 patients, 1141 males and 904 females, were examined in at the Institute of Neonatology over a period of 5 years. The average age was 34.04 gestation weeks. There were significantly more premature (1698 or 83.03%) than term-born babies (347 or 16.97%). Ultrasound hip examination, as a screening method, was carried out according to Graf. It was followed by clinical examination. Results were analyzed by appropriate statistical methods (chi2-test, one-way ANOVA, multifactor ANOVA). The overall frequency of unstable hips was 3.2%, 1.88% in males and 4.87% in females (p<0.05). 96.8% babies had stable hips, out of which 35.21% were mature and 61.59% immature. In the study of the breech presentation, out of 183 babies, unstable hips were found in 1.58% of male cases, and in 10.23% of female cases. Clinical screening of developmental dysplasia of the hip is insufficient for early diagnosis and decision about the treatment of premature babies. The high frequency of unstable hip type IIc (risky) and IId (decentralized) in premature babies requires early diagnosis and therapy. Wide swaddling for prematures should be applied up to eight months of age. Gentle manipulation is necessary while nursing and conducting physiotherapy of a premature baby.

Comparison of Reliability Between the PUMC and Lenke Classification Systems for Classifying Adolescent Idiopathic Scoliosis

Comparison of 2 radiographic scoliosis classification systems by multiple surgeons. Compare the reliability of Peking Union Medical College (PUMC) and Lenke scoliosis classification systems and analyze their differences. The PUMC classification is a newly reported system based on radiographic measurements with recent popularity, while the Lenke classification is widely accepted worldwide in surgical design. Both these classification systems have their own individual characteristics, hence it is necessary to compare their reliability. Five scoliosis surgeons independently evaluated and classified presurgical radiographs of 62 adolescent idiopathic scoliosis patients based on the PUMC and Lenke classification systems on 2 separate occasions. Radiographs were cleaned before each evaluation. Inter- and intraobserver reliabilities were quantified using Kappa statistics. Data were compared using chi2 analysis. The PUMC classification's inter- and intraobserver percentage of agreement averaged to 91.0% (Kappa coefficient 0.896) and 90.2% (Kappa coefficient 0.892), respectively. While those of the Lenke curve type classification were 86.5% (Kappa coefficient 0.808) and 87.4% (Kappa coefficient 0.826). The PUMC classification from 10 individual measurements had 17 cases (27.4%) of disagreements, while in the Lenke curve type classification, 24 cases (38.7%) had disagreements. PUMC classification normally has discrepancies between type IIb, IIc, and IId, while Lenke classification has discrepancies in curve types 1 and 2. Out of 17 inconsistent PUMC curve type cases, 7 did not affect surgical fusion levels, while in the Lenke's only 2 out of 24 cases with discrepancies did not affect fusion range selection, with an obvious statistical difference. The reliability of both PUMC classification and Lenke curve type classification were categorized as good-to-excellent. PUMC classification is relatively simple, with less confusion among inter- and intraobservers, with corresponding surgical fusion guidance and planning. The mismatch of curve classification had less influence on PUMC's fusion range selection than Lenke's.

Changes in types of muscle fibers induced by transcutaneous electrical stimulation of the diaphragm of rats

The objective of the present study was to assess the effect of transcutaneous electrical diaphragmatic stimulation (TEDS) on different types of diaphragm muscle fibers. Male Wistar rats (8-12 weeks old) were divided into 2 experimental groups (N = 8 in each group): 1) control, 2) animals submitted to TEDS [frequency = 50 Hz; T(ON)/T(OFF) (contraction/relaxation time) = 2/2 s; pulse duration = 0.4 ms, intensity = 5 mA with a 1 mA increase every 3 min for 20 min] for 7 days. After completing this treatment period, the I, IIA, IIB, and IID diaphragm muscle fibers were identified using the mATPase technique. Statistical analysis consisted of the normality, homoscedasticity and t-tests (P < 0.05). There was a 19.6% (P < 0.05) reduction in the number of type I fibers and a 49.7% increase (P < 0.05) in type IID fibers in the TEDS group compared with the control group. An important result of the present study was that electrical stimulation with surface electrodes was efficient in altering the distribution of fibers in diaphragm muscle. This therapeutic resource could be used in the treatment of respiratory muscle alterations.

Development assessment of a hip ultrasonographic screening program for the early diagnosis of congenital hip dysplasia at the orthopedic university department Homburg/Saar from 1986 to 1990

The results of the hip ultrasound newborn screening at the orthopaedic department of the University Hospital Homburg/Saar underline the necessity of an early diagnosis of Hip dysplasia already during the first days of life. In the course of the following publication the benefit of using abduction-pants in case of physiological unripe and primary pathological hips is described closely. From October 1985 to December 1990 2317 newborns have been examined by ultrasound. The rate of Hip Dysplasia (type IID, IIg, IIIa) was at 104 hips (2.2%). Clinical striking facts were only found in 46.3% of all patients with primary pathological hips. After an precautionary broad swadling (Breitwickeln) or abduction-pants-treatment 331 (90.0%) hips of the 368 regular checked hips with type IIa developed with an average secondary anatomical healing of 2.5 months to Ia- or Ib-hips. After 3 months only just 12 hips corresponded to a diagnosis of type IIb according to Graf. A deterioration to a IIg or IIIa hip was only ascertained in two cases. With all 41 sufficiently controlled primary pathological hips an improvement to type Ia or Ib according to Graf achieved when treated with abduction pants (average duration of treatment: 4.3 months). None of the children had to undergo an operation because of instable hips.

Sonographic follow-up of hip dysplasia treated with an abduction brace

121 children with cdh, which haven been treated between June 84 and December 85 in our out-patient-ward with Aktivspreizhose (abduction-pants), have been followed by ultrasound examination. Reliability of hip ultrasonography, duration of treatment and results have been evaluated. At the beginning of treatment the diagnosis were: 24.8% type IIa, 29.6% type IIb, 13.2% type IIG or IID and 5.8% type IIIa according to Graf; in 6.6% of the cases cdh was diagnosed only by x-rays. Hip ultrasonography was highly reliable according to quality controls in comparison to x-rays and short-ended the duration of treatment. With the exception of 3 children (1 Myelodysplasia, 2 start of treatment after the 6 months of life) all children with "Aktivspreizhose" treatment showed anatomic healing. Duration of treatment was 4.2 months on the average, 3.5 months when treatment started in the first 3 months of life, and 4.7 months, when started after the first 3 months of life. X-ray-controls at the end of treatment showed mild forms of femoral head necrosis (type I and II) in two cases, which healed completely according to follow up controls. For the treatment of cdh in babies the Aktivspreizhose is the optimal therapy, especially when started in the first 3 months of life. A general legal orthopaedic clinical and ultrasound screening of babies hip in the first week of life should be introduced.

Adiponectin is expressed by skeletal muscle fibers and influences muscle phenotype and function

Adiponectin (Ad) is linked to various disease states and mediates antidiabetic and anti-inflammatory effects. While it was originally thought that Ad expression was limited to adipocytes, we demonstrate here that Ad is expressed in mouse skeletal muscles and within differentiated L6 myotubes, as assessed by RT-PCR, Western blot, and immunohistochemical analyses. Serial muscle sections stained for fiber type, lipid content, and Ad revealed that muscle fibers with elevated intramyocellular Ad expression were consistently type IIA and IID fibers with detectably higher intramyocellular lipid (IMCL) content. To determine the effect of Ad on muscle phenotype and function, we used an Ad-null [knockout (KO)] mouse model. Body mass increased significantly in 24-wk-old KO mice [+5.5 +/- 3% relative to wild-type mice (WT)], with no change in muscle mass observed. IMCL content was significantly increased (+75.1 +/- 25%), whereas epididymal fat mass, although elevated, was not different in the KO mice compared with WT (+35.1 +/- 23%; P = 0.16). Fiber-type composition was unaltered, although type IIB fiber area was increased in KO mice (+25.5 +/- 6%). In situ muscle stimulation revealed lower peak tetanic forces in KO mice relative to WT (-47.5 +/- 6%), with no change in low-frequency fatigue rates. These data demonstrate that the absence of Ad expression causes contractile dysfunction and phenotypical changes in skeletal muscle. Furthermore, we demonstrate that Ad is expressed in skeletal muscle and that its intramyocellular localization is associated with elevated IMCL, particularly in type IIA/D fibers.

Vitreoretinal Surgery for Retinal Detachment in Retinochoroidal Colobomata

To report the management and outcome of retinal reattachment surgery in retinochoroidal coloboma. Four patients with retinochoroidal colobomata presented to the Bristol Eye Hospital (a UK tertiary referral center for vitreoretinal surgery) with retinal detachment. All were type II colobomatous detachments (three patients with type IIB, one patient with type IID). All eyes underwent vitrectomy with endolaser and/or cryotherapy and three eyes underwent scleral buckling. Two eyes had internal tamponade with gas (SF6, C3F8) while the other two had silicone oil. Endolaser was applied over healthy retinal pigment epithelium. At last follow-up, all (100%) remained attached, with no recurrences. Three patients achieved visual acuity of 6/120 or better and were able to perform satisfactory near work with appropriate magnifiers. The last patient began with hand movement vision and retained similar vision but subjectively felt more navigational. Good anatomic and functional outcomes can be achieved in this patient group with combined vitrectomy with or without scleral buckling surgery. Endolaser retinopexy is effective over healthy RPE at the margin of the coloboma combined with either gas or oil internal tamponade.

Effect of show jumping training on the development of locomotory muscle in young horses

To investigate whether training for show jumping that is commenced early after birth affects the characteristics of equine locomotory muscle. 19 Dutch Warmblood horses. Horses were assigned to a trained or not trained (control) group. After weaning, training (free jumping [2 d/wk] that was alternated with a 20-minute period of exercise in a mechanical rotating walker [3 d/wk]) was started and continued until horses were 3 years old. Fiber type composition (determined from myosin heavy chain [MyHC] content), fiber area, diffusion index (area supplied by 1 capillary), citrate synthase activity, and Na(+),K(+)-ATPase content were assessed in gluteus medius muscle specimens collected at 0.5, 1, 2, and 3 years. Developmental changes included an increase in MyHC fiber type IIa and a decrease in type IIad; increases in fiber area, diffusion index, and citrate synthase activity; and a decrease in Na(+),K(+)-ATPase content. The MyHC fiber type I and type IId were detected in high and low proportions, respectively. Training increased Na(+),K(+)-ATPase content, but did not affect other variables. In horses, show jumping training at an early age resulted in increased Na(+),K(+)-ATPase content of the deep portions of the gluteus medius muscle. The lack of training effects on the other muscle characteristics can partly be explained by the fact that an appropriate (aerobic) fiber type composition was already established at training commencement. These data also suggested that the developmental changes in equine muscle represent sufficient adaptation to meet the demands of this specific training.