Biomedical subjects

C C Wang

Publications and source records attributed to C C Wang.

At least 253 records · Page 14Linked to original sources

PubMed1998

Intraoperative Doppler ultrasound in liver transplantation.

The purpose of this study was to determine the utility of intraoperative Doppler ultrasound for the diagnosis and reduction of the vascular complications in liver transplantation. This study included 19 pediatric and 5 adult patients. In the pediatric group, 12 patients received living related liver transplantation (LRLT), two splitting liver transplantation (SLT), three reduced-size liver transplantation (RLT) and two full-size pediatric liver transplants (FPLT). The hemodynamics and waveform of the hepatic vein, portal vein and hepatic artery were evaluated by intraoperative Doppler ultrasound (US) after reperfusion of the graft. Unsatisfactory hemodynamics was identified in nine cases, including decrease hepatic venous flow (6-9 cm/s) with non-pulsative flat waveform (adults, n = 2 and LRLT, n = 2); portal vein thrombosis (LRLT, n = 1); decrease portal flow (8 mL/min/kg) (LRLT, n = 1); occlusion of the portal vein (SLT, n = 1); poor arterial flow with dampened artery waveform (FPLT, n = 2). These abnormalities were all successfully re-reconstructed by surgical procedures and achieved a graft survival rate of 100%. Two late vascular complications including hepatic venous thrombosis and recurrent portal vein stenosis with splenorenal shunt were discovered 1 month later. They were treated effectively by surgical thrombolectomy and percutaneous balloon dilatation and metallic coils embolization respectively. Three patients died of non-vascular complications and all patients who underwent LRLT survived with a resultant 87.5% overall survival rate. In conclusion, intraoperative Doppler US is efficient in detecting abnormal hepatic hemodynamics, which permits early intervention and hence a better prognosis for the patients. Re-reconstructive procedures were monitored closely under Doppler US guidance until proper flow and wave-form were established. This reduces post-transplant vascular complications and thereby eliminates the likelihood of a lethal complication that might call for re-transplantation.

Adolescent↗

PubMed1998

Relative risk of post-transplant renal thrombosis in patients with antiphospholipid antibodies.

INTRODUCTION: Antiphospholipid antibody syndrome (APAS) is a condition associated with recurrent arterial and venous thrombosis, recurrent abortions, and thrombocytopenia either with or without lupus. In this study we have evaluated the impact of APAS on the renal transplant outcome of 174 patients. METHOD: Patients' APAS status was determined by the presence of anticardiolipin antibodies (ACA) and a history of clotting disorders. Serum samples from each patient were tested for the presence of ACA by the ELISA method. Transplant outcomes were monitored for > or = 1 yr. RESULTS: Of 174 patients, 78 received renal transplants. Six of these 78 patients had APAS as evidenced by either recurrent microrenal angiopathy (2 patients), thrombocytopenia (1 patient) or frequent A-V shunt thrombosis (3 patients) along with high titers of ACA of IgM, IgG, or both subtypes at the time of their transplants. Each of these 6 patients thrombosed their renal allografts within a week of their transplants. The other 72 transplanted patients with no APAS were all doing well 1 yr post-transplant. The association between APAS and post-transplant renal thrombosis among these patients is highly significant (p < 0.0001). In contrast, no association was discerned between post-transplant thrombosis and prior sensitization to HLA CONCLUSION: Our data demonstrates that patients with APAS are at high risk for development of post-transplant renal thrombosis.

Adult↗

PubMed1998

Post-transplant changes of segment 4 after living related liver transplantation.

The purpose of this study was to evaluate the outcome of the medial segment of the graft after living related liver transplantation (LRLT). Of the 12 pediatric recipients who underwent LRLT, 2 received whole left liver graft, 1 left lateral segment graft, and 9 extended left lateral segment grafts. The hepatic veins of the donor were reviewed and the volume of the medial segment and left lateral liver was measured before and 6 months after liver transplantation. The flow velocity and direction of the portal vein in the medial segment graft was also evaluated by Doppler ultrasound. The grafted livers of all recipients showed a substantial increase in volume of 9-120% 6 months after LRLT. For the left lateral segment, an increase in volume was found in all cases ranging from 21 to 245%. For the medial segment, volume increases of 5-48% were found in seven cases with normal hepatopetal flow detected inside the segment 4 intrahepatic portal vein. In four cases, the partial medial segment graft of the extended left lateral liver graft decreased in volume from 33 to 69%. Among these four cases, slow flow (n = 2) and hepatofugal flow (n = 1) were also detected in the intrahepatic portal vein of the medial segment. Mapping of the tributary of the hepatic veins of the graft revealed inadequate venous drainage of the partial segment 4 graft, which may be considered as the cause of the atrophic change of the partial segment 4 graft. In conclusion, different regenerative rates between the left lateral segment and the medial segment were noted, with a greater rate in the left lateral segment. The venous drainage of the medial segment is of primary concern in the determination of the outcome of the regeneration. Atrophic change occurs when inadequate hepatic venous drainage is encountered. Therefore, if an extended left lateral liver graft is required, the corresponding draining veins of the partial medial segment must be preserved. Otherwise, whole left liver or left lateral segment graft would be a better choice.

Blood Flow Velocity↗

PubMed1997

Inhibition of proteasome activity blocks cell cycle progression at specific phase boundaries in African trypanosomes.

Proteasomes are one of the cellular complexes controlling protein degradation from archaebacteria to mammalian cells. We recently purified and characterized the catalytic core of the proteasome, the 20S form, from Trypanosoma brucei, a flagellated protozoa which causes African trypanosomiasis. To identify the role of proteasomes in African trypanosomes, we used lactacystin, a specific inhibitor of proteasome activity. Lactacystin showed potent inhibition of the activity of 20S proteasomes purified from both bloodstream and procyclic (insect) forms of T. brucei (IC50 = 1 microM). It also inhibited proliferation of T. brucei cells in culture assays, with 1 microM inhibiting growth of bloodstream forms, whereas 5 microM was required to block proliferation of procyclic forms. Analysis of the DNA content of these cells by flow cytometry showed that 5 microM lactacystin arrested procyclic cells in the G2 + M phases of the cell cycle. Fluorescence microscopy revealed that most of the cells had one nucleus and one kinetoplast each, indicating that the cells had replicated their DNA, but failed to undergo mitosis. This suggests that transition from G2 to M phase was blocked. On the other hand, incubation of bloodstream forms with 1 microM lactacystin led to arrest of 30-35% of the cell population in G1 and 55-60% of the cells in G2, indicating that both transition from G1 to S and from G2 to M were blocked. These observations were also confirmed by using another inhibitor of proteasome, N-carbobenzoxy-L-leucyl-L-leucyl-L-norvalinal (LLnV), which arrested procyclic forms in G2, and bloodstream forms in both G1 and G2. These results suggest that proteasome activity is essential for driving cell cycle progression in T. brucei, and that proteasomes may control cellular functions differently in bloodstream and procyclic forms of T. brucei.

Acetylcysteine↗

PubMed1997

Adenosine-sensitive ventricular tachycardia from the anterobasal left ventricle.

OBJECTIVES: This study demonstrates that exercise-provocable tachycardia resembling right ventricular outflow tract tachycardia may originate from the anterobasal left ventricle. BACKGROUND: Reentry is the operative mechanism of idiopathic left ventricular tachycardia, with a QRS complex of right bundle branch block and superior axis that is responsive to verapamil but not adenosine. Whether some mechanism other than reentry is operative in some idiopathic left ventricular tachycardias is unclear. METHODS: In 4 of 53 consecutive patients with idiopathic left ventricular tachycardia, the tachycardia was sensitive to adenosine. These four patients were women 63, 61, 61 and 31 years old and were the subjects of the present study. RESULTS: In all four patients, spontaneous tachycardia was related to exercise or emotional stress. The tachycardia displayed atypical left (one patient) or right (three patients) bundle branch block with an inferior axis and marked variation in cycle length. An intravenous bolus of adenosine triphosphate (10 to 20 mg) terminated tachycardia in all four patients. Tachycardia was terminated or prevented in three patients given intravenous or oral verapamil. Atrial or ventricular incremental or extrastimulus testing induced tachycardia in all four patients (three with, one without isoproterenol infusion). Electrically induced tachycardia also demonstrated marked variation in cycle length, which ranged from 230 to 390 ms. Entrainment was not demonstrable with overdrive pacing from multiple sites. Endocardial mapping during tachycardia revealed that the earliest activations were registered 25, 40, 35 and 50 ms before onset of the QRS complex, respectively, from the anterior aspect of the left ventricle just below the mitral annulus, adjacent to the left ventricular outflow tract. High frequency Purkinje spikes were not recorded at this site. Radiofrequency current delivered to this site successfully ablated the tachycardia in three of the four patients. CONCLUSIONS: Exercise-provocable, catecholamine-mediated, verapamil-responsive, adenosine-sensitive ventricular tachycardia may arise from the anterobasal left ventricle adjacent to the outflow tract.

Adenosine↗

PubMed1997

Labeling reactions applicable to chromatography and electrophoresis of minute amounts of proteins.

Chromatography and electrophoresis have become extremely valuable and important methods for the separation, purification, detection and analysis of biopolymers and HPLC/HPCE may become the premier, preferable approaches for both qualitative and quantitative analyses of most proteins, especially from recombinant materials. This includes smaller peptides, polypeptides, proteins, antibodies and all types of protein or antibody-conjugates (antibody-enzyme, protein-fluorescent probe, antibody-drug and so forth). This entire Topical Issue of Journal of Chromatography emphasizes the application of chromatography and electrophoresis to protein analysis. This particular review deals with approaches to the selective tagging or labeling of proteins at trace (minute) levels, again using either chromatography or electrophoresis, with the emphasis on modern HPLC/HPCE methods and approaches. We discuss here both pre- and post-column labeling methods and reagents, techniques for realizing selective labeling of proteins or antibodies, applicable approaches to protein preconcentration in both HPLC and HPCE areas and in general, methods for improving (lowering) detection limits for proteins utilizing chemical or physical derivatization and/or preconcentration techniques. There are really two major goals or emphases in that which follows: (1) methods for selective labeling of proteins prior to or after HPLC/HPCE and (2) labeling of proteins at trace levels for improved separation-detection and lowered detection limits. We discuss here a large number of specific references related to both pre- and post-column/capillary derivatizations for proteins, as well as methods for improved detectability in both HPLC and HPCE by, for example, analyte preconcentration on a solid-phase extractor or membrane support, capillary isotachophoresis and other methods. Selective reactions or derivatizations on proteins refers to the ability to tag the protein at specific (e.g. reactive amino sites) in a controlled manner, with the products having the same number of tags all at the very same site or sites. The products are all the same species, having the same number of tags at the same locations on the protein. Selective reactions can also refer to the idea of tagging all of the protein sample at only a single, same site or at all available sites, homogeneously.

Animals↗

PubMed1997

Crystal structure of Tritrichomonas foetus inosine-5'-monophosphate dehydrogenase and the enzyme-product complex.

Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for the control of parasitic infections. The enzyme catalyzes the oxidation of inosine monophosphate (IMP) to xanthosine monophosphate (XMP), the committed step in de novo guanosine monophosphate (GMP) biosynthesis. We have determined the crystal structures of IMPDH from the protozoan parasite Tritrichomonas foetus in the apo form at 2.3 A resolution and the enzyme-XMP complex at 2.6 A resolution. Each monomer of this tetrameric enzyme is comprised of two domains, the largest of which includes an eight-stranded parallel beta/alpha-barrel that contains the enzyme active site at the C termini of the barrel beta-strands. A second domain, comprised of residues 102-220, is disordered in the crystal. IMPDH is expected to be active as a tetramer, since the active site cavity is formed by strands from adjacent subunits. An intrasubunit disulfide bond, seen in the crystal structure, may stabilize the protein in a less active form, as high concentrations of reducing agent have been shown to increase enzyme activity. Disorder at the active site suggests that a high degree of flexibility may be inherent in the catalytic function of IMPDH. Unlike IMPDH from other species, the T. foetus enzyme has a single arginine that is largely responsible for coordinating the substrate phosphate in the active site. This structural uniqueness may facilitate structure-based identification and design of compounds that specifically inhibit the parasite enzyme.

Amino Acid Sequence↗

PubMed1997

Retention of replication fidelity by a DNA polymerase functioning in a distantly related environment.

The primary structures of the replicative DNA polymerases (gp43s) of bacteriophage T4 and its distant phylogenetic relative RB69 are diverged, retaining only 61% identity and 74% similarity. Nevertheless, RB69 gp43 substitutes effectively for T4 gp43 in T4 DNA replication in vivo. We show here that RB69 gp43 replicates T4 genomes in vivo with a fidelity similar to that achieved by T4 gp43. Furthermore, replication by RB69 gp43 in the distantly related environment does not enhance the mutator activities of mutations in T4 genes that encode other components of the multienzyme DNA replicase. We also show that the fidelities of RB69 gp43 and T4 gp43 are both high in vitro and that they are similarly and sharply reduced in vivo by mutations that eliminate the 3'-exonucleolytic proofreading function. We conclude that gp43 interactions with the other replication proteins are probably nonessential for polymerase fidelity.

Bacteriophage T4↗

PubMed1997

Evolution of RNA-binding specificity in T4 DNA polymerase.

DNA polymerase of phage T4 (T4 gp43), an essential component of the T4 DNA replicase, is a multifunctional single-chained (898-amino acid) protein that catalyzes the highly accurate synthesis of DNA in phage replication. The enzyme functions both as a DNA-binding replication protein and as a sequence-specific RNA-binding autogenous translational repressor. We have utilized a phylogenetic approach to study the relationships between the two nucleic acid-binding functions of the protein. We found that autogenous translational control of gp43 biosynthesis has been conserved in phage RB69, a distant relative of T4, although we also found that the RB69 system differs from its T4 counterpart in two regards: (a) nucleotide sequence and predicted secondary structure of the RNA target (translational operator), and (b) RNA specificity of the protein. T4 gp43 is specific to the RNA operator sequence of the T4 genome whereas RB69 gp43 can bind and repress operator RNA from both phages equally well. In studies with T4-RB69 gp43 chimeras, we mapped T4 gp43 RNA-binding specificity to a protein segment that also harbors important determinants for DNA binding and the polymerase catalytic function. Our results suggest that RNA functions as a regulator of both the dosage and activity of this DNA replication enzyme.

Bacteriophage T4↗

PubMed1997

Crystal structure of a pol alpha family replication DNA polymerase from bacteriophage RB69.

The 2.8 A resolution crystal structure of the bacteriophage RB69 gp43, a member of the eukaryotic pol alpha family of replicative DNA polymerases, shares some similarities with other polymerases but shows many differences. Although its palm domain has the same topology as other polymerases, except rat DNA polymerase beta, one of the three carboxylates required for nucleotidyl transfer is located on a different beta strand. The structures of the fingers and thumb domains are unrelated to all other known polymerase structures. The editing 3'-5' exonuclease domain of gp43 is homologous to that of E. coli DNA polymerase I but lies on the opposite side of the polymerase active site. An extended structure-based alignment of eukaryotic DNA polymerase sequences provides structural insights that should be applicable to most eukaryotic DNA polymerases.

Bacteriophages↗

PubMed1997

Mutant human protein disulfide isomerase assists protein folding in a chaperone-like fashion.

Human protein disulfide isomerase with an extra 10 amino acid residues of AEITRIDPAM at the N-terminal was expressed in E. coli as a soluble protein comprising 20% of total cell proteins, and was purified to near homogeneity through one step of DEAE-Sephacel chromatography. The mutant enzyme, which had the same CD spectrum and comparable disulfide isomerase and thiol-protein oxidoreductase activities with that of the wild type human and bovine protein disulfide isomerases, also showed chaperone-like activity in stimulating the refolding of proteins containing no disulfide bond. The overall yield of the active product is about 20 mg 1-1 culture.

Amino Acid Sequence↗

PubMed1997

Interferon-gamma activation of a mitogen-activated protein kinase, KFR1, in the bloodstream form of Trypanosoma brucei.

KFR1, a mitogen-activated protein (MAP) kinase identified in the African trypanosome, Trypanosoma brucei, is a serine protein kinase capable of phosphorylating the serine residues in histone H-1, myelin basic protein, and beta-casein. It phosphorylates four proteins with estimated molecular masses of 22, 34, 46, and 90 kDa from the T. brucei bloodstream-form lysate in vitro. KFR1 bears significant sequence similarity to the yeast MAP kinases KSS1 and FUS3 but cannot functionally complement the kss1/fus3 yeast mutant. It is encoded by a single-copy gene in the diploid T. brucei, and only one of the two alleles can be successfully disrupted, suggesting an essential function of KFR1 in T. brucei. KFR1 activity is present at a much enhanced level in the bloodstream form of T. brucei when compared with that in the insect (procyclic) form. This enhanced activity can be eliminated in vitro by the treatment with protein phosphatase HVH2 known to act specifically on MAP kinases. It can also be decreased in the bloodstream form of T. brucei by serum starvation but induced specifically by interferon-gamma. The production of interferon-gamma in the mammalian host is known to be triggered by T. brucei infection, and this cytokine, as has been reported, promotes the proliferation of T. brucei in the mammalian blood. Since none of these phenomena can be observed in the procyclic form of T. brucei, activation of KFR1 is most likely involved in mediating the interferon-gamma-induced proliferation of T. brucei in the mammalian host.

Animals↗

PubMed1997

Identification of the major casein kinase I phosphorylation sites on erythrocyte band 3.

Human erythrocyte band 3 is a major substrate of two red blood cell protein kinases, casein kinase I and p72syk protein tyrosine kinase. Although the phosphorylation sites and physiologic consequences of p72syk phosphorylation have been characterized, little is known regarding casein kinase I phosphorylation. In this report, we identify the major phosphorylation site of casein kinase I. Using isolated components, casein kinase I was found to phosphorylate the cytoplasmic domain of band 3 (CDB3), primarily on Thr residues. Classical peptide mapping narrowed the major phosphorylation site to a peptide encompassing residues 24-91. Computer-assisted evaluation of this sequence not only showed two consensus casein kinase I phosphorylation sites, but also provided information on how to proteolytically separate and isolate the candidate sites. Following the suggested protocols, a heptapeptide containing the major phosphorylation site was isolated, subjected to amino acid sequencing, and found to be phosphorylated on Thr 42. A minor phosphorylation site was similarly identified as Ser 303. Because Thr 42 is situated near the binding sites on CDB3 of ankyrin, protein 4.1, protein 4.2, and the glycolytic enzymes, phosphorylation of CDB3 by casein kinase I could conceivably impact erythrocyte structure and/or function.

Amino Acid Sequence↗

PubMed1997

Inactivation of Tritrichomonas foetus and Schistosoma mansoni purine phosphoribosyltransferases by arginine-specific reagents.

The arginine-specific reagents phenylglyoxal and butane-2,3-dione irreversibly inactivate the Tritrichomonas foetus hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) and Schistosoma mansoni hypoxanthine-guanine phosphoribosyltransferase (HGPRT). The inactivation of the tritrichomonal enzyme by phenylglyoxal follows time-dependent and concentration-dependent pseudo-first-order kinetics. Complete protection against inactivation is afforded by the addition of 25 microM GMP, whereas 5-phosphoribosyl-1-diphosphate (PRibPP) at 50-250 microM can only slow down the inactivation, without being protective. Digestion of [7-(14)C]phenylglyoxal-modified enzyme with trypsin and separation of the peptides by reverse-phase HPLC shows that only one radioactive peak is greatly diminished by incubation with 25 microM GMP or 1 mM PRibPP. Mass-spectral analysis identifies Arg155 as the target site of two molecules of phenylglyoxal that is protected by the substrates. This amino acid residue is positioned next to Tyr156, which is a highly conserved aromatic residue among all the purine phosphoribosyltransferases (PRT) and is always found stacked on top of the purine substrate. This may explain why phenylglyoxal labeling of Arg155 inactivates the enzyme and why GMP can protect Arg155 more effectively than PRibPP. Among the purine PRT in our possession, only schistosomal HGPRT, the only other enzyme that contains an arginine residue at the corresponding location (Arg187), was susceptible to phenylglyoxal and butane-2,3-dione. The presence of Lys185-Phe186 and Ser179-Trp180 at the corresponding locations in human HGPRT and Giardia lamblia GPRT, respectively, may explain their resistance to phenylglyoxal. Thus, Arg155 in T. foetus HGXPRT and Arg187 in S. mansoni HGPRT will be attractive targets for future studies.

Amino Acid Sequence↗

PubMed1997

Identification and characterization of an activated 20S proteasome in Trypanosoma brucei.

Recently, we have reported the isolation and purification of 20S proteasomes from both the procyclic and bloodstream forms of Trypanosoma brucei, but no 26S proteasome was identified under those experimental conditions (Hua et al., Mol. Biochem. Parasitol. (1996) 78, 33-46). Subsequent attempts to identify a 26S proteasome in T. brucei led to the discovery of another form of the 20S proteasome designated the activated 20S proteasome because it exhibited much higher peptidase activities than the original 20S proteasome on all the fluorogenic peptides tested, and it crossreacted with the rabbit antisera against the 20S proteasomes purified from T. brucei. The activated 20S proteasome can be isolated from both procyclic and bloodstream forms of T. brucei and has a slightly higher molecular weight than the 20S proteasome. It is stable in the absence of ATP but susceptible to elution through a DE52 column. Analysis of the activated 20S proteasome in SDS-PAGE showed the presence of all the subunit proteins from the 20S proteasome plus an extra protein with an estimated molecular mass of 26 kDa. This protein, designated PA26, is not a degradation product of the 20S proteasomal subunit proteins. It could be a homolog of the bovine PA28 and human 11S regulator protein which form complexes with the 20S proteasomes resulting in activation of their peptidase activities. This likelihood was confirmed in a reconstitution experiment in which PA26 separated from the proteasome by a DE52 column chromatography was re-introduced into the purified 20S proteasome, and resulted in the emergence of a new protein band with the same mobility and peptidase activities as the activated 20S proteasome in native polyacrylamide gel electrophoresis. The presence of an activated 20S proteasome rather than a homolog of the 26S proteasome in T. brucei suggests that PA26 may play an important role in regulating the proteasome-mediated protein degradations in trypanosomes.

Adenosine Triphosphate↗

PubMed1997

The mouse formin (Fmn) gene: genomic structure, novel exons, and genetic mapping.

Mutations in the mouse formin (Fmn) gene, formerly known as the limb deformity (ld) gene, give rise to recessively inherited limb deformities and renal malformations or aplasia. The Fmn gene encodes many differentially processed transcripts that are expressed in both adult and embryonic tissues. To study the genomic organization of the Fmn locus, we have used Fmn probes to isolate and characterize genomic clones spanning 500 kb. Our analysis of these clones shows that the Fmn gene is composed of at least 24 exons and spans 400 kb. We have identified two novel exons that are expressed in the developing embryonic limb bud as well as adult tissues such as brain and kidney. We have also used a microsatellite polymorphism from within the Fmn gene to map it genetically to a 2.2-cM interval between D2Mit58 and D2Mit103.

Amino Acid Sequence↗

PubMed1997

Does DsbA have chaperone-like activity?

DsbA showed chaperone-like activity similar to but weaker than that of protein disulfide isomerase in increasing reactivation and decreasing aggregation during the refolding of guanidine hydrochloride-denatured D-glyceraldehyde-3-phosphate dehydrogenase and rhodanese. The fact that both enzymes are devoid of disulfide bonds indicates the independence of the chaperone-like activity of DsbA from its thiol-protein oxidoreductase activity. The increased reactivation of D-glyceraldehyde-3-phosphate dehydrogenase by DsbA can be suppressed with increasing concentrations of a peptide of 21 amino acid residues, suggesting that the peptide binding ability of DsbA is responsible for its chaperone-like activity.

Glyceraldehyde-3-Phosphate Dehydrogenases↗

PubMed1997

Childhood-onset autosomal-dominant limb-girdle muscular dystrophy with cardiac conduction block.

We report childhood-onset autosomal-dominant limb-girdle muscular dystrophy (LGMD) in a Chinese family with complete atrioventricular conduction block in the adult members. Six patients, including 5 men and 1 woman with an age of onset from 3 to 7 years, were affected. The grandfather had exercise intolerance since childhood and complete heart block with pace-maker placement at age 52. Three siblings had proximal muscle weakness and/or wasting since age 5 and heart block in their 40s. Two grandsons at the ages 7 and 3 showed exercise intolerance, and proximal muscle weakness and wasting. Sinus bradycardia was present in the elder grandson. Muscle enzymes were elevated in 3, particularly in childhood. Muscle biopsies from the proband showed myopathic changes with fatty degeneration, whorled fibers, and rimmed vacuoles. In adult patients, muscle magnetic resonance imaging scans disclosed atrophic changes and fatty degeneration in the gluteal, quadriceps, adductors, hamstrings, gastrocnemius, and soleus muscles, while in child probands the early atrophic changes were seen in the gluteal and hamstrings muscles. We conclude that this distinct family is characterized by childhood-onset autosomal-dominant LGMD with heart block and that prevention of sudden death in these patients is important.

Adolescent↗