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Biomedical subjects

M H Gollob

Publications and source records attributed to M H Gollob.

7 recordsLinked to original sources
PubMed2003

Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome.

The AMP-activated protein kinase (AMPK) system was first discovered 30 years ago. Since that time, knowledge of the diverse physiological functions of AMPK has grown rapidly and continues to evolve. Most recently, the observation that spontaneously occurring genetic mutations in the gamma regulatory subunits of AMPK give rise to a skeletal and cardiac muscle disease emphasizes the critical importance of AMPK in the maintenance of health and disease. The cardiac phenotype observed in humans harbouring genetic mutations in the gamma 2 regulatory subunit (PRKAG2) of AMPK is consistent with abnormal glycogen accumulation in the heart. The perturbation of AMPK activity induced by genetic mutations in PRKAG2 and the resultant effect on muscle cell glucose metabolism may be relevant to the issue of targeting AMPK in drug development for insulin-resistant diabetes mellitus.

AMP-Activated Protein Kinases↗
PubMed2001

Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy.

BACKGROUND: We recently reported a mutation in the PRKAG2 gene to be responsible for a familial syndrome of ventricular preexcitation, atrial fibrillation, conduction defects, and cardiac hypertrophy. We now report a novel mutation in PRKAG2 causing Wolff-Parkinson-White syndrome and conduction system disease with onset in childhood and the absence of cardiac hypertrophy. METHODS AND RESULTS: DNA was extracted from white blood cells obtained from family members. PRKAG2 exons were amplified by polymerase chain reaction and were screened for mutations by direct sequencing. The genomic organization of the PRKAG2 gene was determined using inter-exon long-range polymerase chain reaction for cDNA sequence not available in the genome database. A missense mutation, Arg531Gly, was identified in all affected individuals but was absent in 150 unrelated individuals. The PRKAG2 gene was determined to consist of 16 exons and is at least 280 kb in size. CONCLUSIONS: We identified a novel mutation (Arg531Gly) in the gamma-2 regulatory subunit (PRKAG2) of AMP-activated protein kinase (AMPK) to be responsible for a syndrome associated with ventricular preexcitation and early onset of atrial fibrillation and conduction disease. These observations confirm an important functional role of AMPK in the regulation of ion channels specific to cardiac tissue. The identification of the cardiac ion channel(s) serving as substrate for AMPK not only would provide insight into the molecular basis of atrial fibrillation and heart block but also may suggest targets for the development of more specific therapy for these common rhythm disturbances.

AMP-Activated Protein Kinases↗
PubMed2001

Identification of a gene responsible for familial Wolff-Parkinson-White syndrome.

BACKGROUND: The Wolff-Parkinson-White syndrome, with a prevalence in Western countries of 1.5 to 3.1 per 1000 persons, causes considerable morbidity and may cause sudden death. We identified two families in which the Wolff-Parkinson-White syndrome segregated as an autosomal dominant disorder. METHODS: We studied 70 members of the two families (57 in Family 1 and 13 in Family 2). The subjects underwent 12-lead electrocardiography and two-dimensional echocardiography. Genotyping mapped the gene responsible to 7q34-q36, a locus previously identified to be responsible for an inherited form of Wolff-Parkinson-White syndrome. Candidate genes were identified, sequenced, and analyzed in normal and affected family members to identify the disease-causing gene. RESULTS: A total of 31 members (23 from Family 1 and 8 from Family 2) had the Wolff-Parkinson-White syndrome. Affected members of both families had ventricular preexcitation with conduction abnormalities and cardiac hypertrophy. The maximal combined two-point lod score was 9.82 at a distance of 5 cM from marker D7S636, which confirmed the linkage of the gene in both families to 7q34-q36. Haplotype analysis indicated that there were no alleles in common in the two families at this locus, suggesting that the two families do not have a common founder. We identified a missense mutation in the gene that encodes the gamma2 regulatory subunit of AMP-activated protein kinase (PRKAG2). The mutation results in the substitution of glutamine for arginine at residue 302 in the protein. CONCLUSIONS: The identification of this genetic defect has important implications for elucidating the pathogenesis of ventricular preexcitation. Further understanding of how this molecular defect leads to supraventricular arrhythmias could influence the development of specific therapies for other forms of supraventricular arrhythmia.

AMP-Activated Protein Kinases↗
PubMed2001

Current status of the implantable cardioverter-defibrillator.

Clinical trials have established the superiority of the implantable cardioverter-defibrillator (ICD) over antiarrhythmic drug therapy in survivors of sudden cardiac death and in high-risk patients with coronary artery disease. The ICD has evolved to overcome the limitation of earlier devices that required thoracotomy for implantation and were fraught with inappropriate shock delivery. Current ICDs are implanted in a similar manner to cardiac pacemakers and incorporate sophisticated rhythm-discrimination algorithms to prevent inappropriate therapy. Managing the patient with an ICD requires an understanding of the multiprogrammable features of modern devices. Drug interactions and potential sources of electromagnetic interference may adversely affect ICD function. Driving restrictions may be necessary under certain conditions. The cost-effectiveness of ICD therapy appears favorable, given the marked survival benefit seen in randomized trials relative to antiarrhythmic drug treatment. The growing number of ICD recipients necessitates an understanding of the specialized features of the modern ICD and the role of device therapy in clinical practice.

Anti-Arrhythmia Agents↗
PubMed2000

Accessory atrioventricular node with properties of a typical accessory pathway: anatomic-electrophysiologic correlation.

We report an accessory AV node producing ventricular preexcitation and comprising the retrograde limb of AV reentrant tachycardia (AVRT). A 66-year-old man presented with an anteroseptal myocardial infarction and thereafter developed recurrent, drug-refractory AVRT requiring multiple cardioversions. Electrophysiologic findings were typical for a concealed anteroseptal accessory pathway 0.5 cm anterior to the His bundle. The patient died of intractable heart failure after endocardial resection for a left ventricular aneurysm and coronary bypass grafting. Pathologic examination revealed a para-Hisian accessory AV node connecting the right atrium to ventricular myocardium immediately anterior to the His bundle at a depth of 4 mm from the endocardium. No typical AV accessory pathway was found. This is the first report of an accessory AV node that participated in AVRT. It was deeper than typical radiofrequency catheter ablation lesions.

Aged↗
PubMed1998

Postradiation morphea.

We describe a 54-year-old woman who developed right breast morphea after radiotherapy following a lumpectomy for infiltrating lobular carcinoma. Skin biopsy confirmed the histological features of morphea. Treatment was initiated with both topical and intralesional steroid, resulting in marked improvement. Morphea following radiotherapy is an infrequently recognized phenomenon. However, when diagnosed early it may be effectively managed with local steroid treatment.

Administration, Topical↗