Pompe disease is a severe form of muscular dystrophy due to glycogen accumulation in all tissues, especially striated muscle. Disease severity is directly related to the deficiency of acid ␣-glucosidase (GAA), which degrades glycogen in the lysosome. Respiratory dysfunction is a hallmark of the disease, muscle weakness has been viewed as the underlying cause, and the possibility of an associated neural contribution has not been evaluated previously. Therefore, we examined behavioral and neurophysiological aspects of breathing in 2 animal models of Pompe disease-the Gaa ؊/؊ mouse and a transgenic line (MTP) expressing GAA only in skeletal muscle, as well as a detailed analysis of the CNS in a Pompe disease patient. Glycogen content was elevated in the Gaa ؊/؊ mouse cervical spinal cord. Retrograde labeling of phrenic motoneurons showed significantly greater soma size in Gaa ؊/؊ mice vs. isogenic controls, and glycogen was observed in Gaa ؊/؊ phrenic motoneurons. Ventilation, assessed via plethysmography, was attenuated during quiet breathing and hypercapnic challenge in Gaa ؊/؊ mice (6 to >21 months of age) vs. controls. We confirmed that MTP mice had normal diaphragmatic contractile properties; however, MTP mice had ventilation similar to the Gaa ؊/؊ mice during quiet breathing. Neurophysiological recordings indicated that efferent phrenic nerve inspiratory burst amplitudes were substantially lower in Gaa ؊/؊ and MTP mice vs. controls. In human samples, we demonstrated similar pathology in the cervical spinal cord and greater accumulation of glycogen in spinal cord compared with brain. We conclude that neural output to the diaphragm is deficient in Gaa ؊/؊ mice, and therapies targeting muscle alone may be ineffective in Pompe disease.glycogenosis ͉ motor neuron ͉ muscular dystrophy ͉ myopathy

(Circulation 1989;79:549-556) E xperimental studies in animals demonstrate that neutrophils play important roles in the pathophysiology of myocardial ischemia and infarction.1-5 Several epidemiologic studies in human subjects also indicate the relevance of leukocytes in ischemic heart disease. Elevation of leukocyte count in peripheral blood is associated with increased risk of acute myocardial infarction,6-10 its recurrence,1 and the incidence of ventricular fibrillation in the postinfarction period.12 Leukocyte count has also been shown to correlate with the extent of coronary artery disease observed at coronary angiography.13

We report the case of a hepatic undifferentiated (embryonal) sarcoma (UES) arising within a mesenchymal hamartoma (MH) in a 15-year-old girl. Mapping of the tumor demonstrated a typical MH transforming gradually into a UES composed of anaplastic stromal cells. When evaluated by flow cytometry, the MH was diploid and the UES showed a prominent aneuploid peak. Karyotypic analysis of the UES showed structural alterations of chromosome 19, which have been implicated as a potential genetic marker of MH. The histogenesis of MH and UES is still debated, and reports of a relationship between them, although suggested on the basis of histomorphologic similarities, have never been convincing. The histologic, flow cytometric, and cytogenetic evidence reported herein suggests a link between these two hepatic tumors of the pediatric population.

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Class II, and perhaps class I HLA antibodies at relatively low concentrations represent a risk factor for severe early pulmonary graft dysfunction, with the potential to progress to hyperacute rejection and death.

Previous studies indicate impairment of coronary arterial ring relaxation in response to acetylcholine (ACh) following coronary reperfusion, mediated via loss of endothelium-derived relaxing factor (EDRF). To examine if coronary vasodilator reserve is reduced following coronary ocdusionreperfusion in intact animnk, 16 open-chest mongrel dogs were subjected to 1 hour of total left circumflex (Cx) coronary artery ocduskm followed by reperfusion for 1 hour. Prior to Cx occlusion, coronary blood flow increased and vascular resistance decreased (both p<0.01) in response to ACh and bradykinin (BK). Following reperfusion, increase in Cx coronary flow in response to both vasodilators was significantly (p^O.Ol) unpaired. Myocardial histology showed extensive neutrophil infiltration and capillary plugging by neutrophils in the Cx compared with the left anterior descending coronary artery-supplied myocardium. Myocardial myeloperoxidase activity was also increased in the Cx compared with the left anterior descending region (p<0.02). Pretreatment of four dogs with indomethadn partially reduced the vasodilator response to BK but not to ACh. However, indomethadn did not affect reperfusion-induced attenuation of BK or ACh's coronary vasodilator effects. To determine if calcium blocker verapamil would modify reperfusion-induced impairment in coronary vasodilator reserve, six dogs were treated with verapamil. Although verapamfl enhanced coronary vasodilator effects of ACh and BK, it did not modify reperfusioninduced attenuation of coronary vasodilator reserve. Myocardial neutrophil accumulation and myeloperoxidase activity was also similar in control, indomethadn, and verapamil-treated dogs. These observations suggest that coronary reperfusion impairs coronary vasodilator reserve in intact dogs. This impairment is not modified by prostaglandin inhibition or by caldum blockade. Received February 22, 1988; accepted June 15, 1988. relaxation evoked by acetylcholine (ACh). Subsequent studies showed that the coronary artery ring relaxation by thrombin is converted to constriction when dog coronary arteries are subjected to total occlusion followed by reperfusion. 5 VanBenthuysen et al 6 have also shown attenuation of ACh-induced relaxation of coronary arterial rings from dogs subjected to temporary coronary occlusion. In those studies, electron microscopy demonstrated focal areas of endothelial cell injury with partial detachment of the cells from the underlying subendothelium.Recent studies have shown extensive capillary plugging by neutrophils in the myocardium of dogs following coronary occlusion and reperfusion, 78 which may relate to the microvascular origin of the "no-reflow" phenomenon. 9 Neutrophil capillary plugging reduces the cross-sectional area of the microvascular bed and could reduce coronary vasodilator reserve. Bradykinin (BK) dilates coronary arteries in a dose-dependent manner by stimulating release of EDRF as well as another potent vasodilator from the vessel wall, prostacyclin (PGI2).10 " Pretreatment of t...

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