Showing papers by "Anthony A. Amato published in 1998"

Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy

Abstract: Miyoshi myopathy (MM) is an adult onset, recessive inherited distal muscular dystrophy that we have mapped to human chromosome 2p13. We recently constructed a 3-Mb P1-derived artificial chromosome (PAC) contig spanning the MM candidate region. This clarified the order of genetic markers across the MM locus, provided five new polymorphic markers within it and narrowed the locus to approximately 2 Mb. Five skeletal muscle expressed sequence tags (ESTs) map in this region. We report that one of these is located in a novel, full-length 6.9-kb muscle cDNA, and we designate the corresponding protein 'dysferlin'. We describe nine mutations in the dysferlin gene in nine families; five are predicted to prevent dysferlin expression. Identical mutations in the dysferlin gene can produce more than one myopathy phenotype (MM, limb girdle dystrophy, distal myopathy with anterior tibial onset).

Neuropathies associated with malignancy.

Abstract: Patients with malignancy can develop peripheral neuropathies as (1) a direct effect of the cancer by invasion or compression of nerves, (2) a remote or paraneoplastic effect, or (3) an iatrogenic effect of treatment. Focal or multifocal cranial neuropathies, radiculopathies, and plexopathies typically result from tumor infiltration, herpes zoster infection, or radiation-induced injury. Sensorimotor polyneuropathies are the most frequently encountered peripheral nerve syndromes, but motor neuropathies, sensory neuronopathies, polyradiculoneuropathies, and autonomic neuropathies can also occur. Although uncommon, paraneoplastic mechanisms should be considered in a patient with malignancy and an associated peripheral nerve disorder, especially in the setting of small-cell lung cancer or lymphoproliferative cancer. Toxic neuropathies occur with exposure to several chemotherapeutic agents, including the vinca alkaloids, cisplatin, taxanes, and suramin. These neuropathies are usually dose-related, sensory-predominant, and at least partially reversible, with an axonopathic or ganglionopathic mechanism. Suramin is unique in causing subacute, demyelinating polyradiculoneuropathy.

The wide spectrum of myofibrillar myopathy suggests a multifactorial etiology and pathogenesis

Abstract: Background: Myofibrillar myopathy (MFM) is characterized by nonhyaline lesions (foci of myofibrillar destruction) and hyaline lesions (cytoplasmic inclusions composed of compacted myofibrillar residues) on light and electron microscopy. Immunocytochemistry demonstrates the abnormal expression of desmin and numerous other proteins. The clinical, laboratory, and histologic features of MFM are heterogeneous, making a diagnosis difficult. Results: We diagnosed eight patients with MFM over the preceding 3 years. MFM was inherited in an autosomal dominant pattern in one patient, developed sporadically in five patients, and was induced by an experimental chemotherapy, Elinafide (Knoll, Parsippany, NJ), in two patients. Age at onset ranged from 14 to 64 years. The pattern of weakness was variable but involved proximal and distal muscles. Five patients had evidence of a cardiomyopathy. Electromyography demonstrated muscle membrane instability and small, polyphasic motor unit potentials. Serum creatine kinase levels were normal to moderately elevated ( Conclusions: Patients demonstrate a wide spectrum of clinical, laboratory, and histologic abnormalities. Chemotherapy-induced MFM has abnormalities on immunocytochemistry similar to the those of hereditary and sporadic cases. The pathogenesis of MFM is likely heterogeneous. However, MFM is distinctive in that it can preferentially affect distal muscles and has a frequent association with cardiomyopathy. The cardiomyopathy may be amenable to treatment with pacemaker insertion or cardiac transplantation.

Primary hyperparathyroidism and ALS: is there a relation?

Abstract: Background An association between primary hyperparathyroidism (PHP) and amyotrophic lateral sclerosis (ALS) has been noted; however, a causal relation between these disorders has not been confirmed. Patients/ Methods We report five patients (three men, two women) meeting El Escorial criteria for ALS who also had PHP. In three patients, the diagnosis of PHP was made during the laboratory evaluation for motor neuron disease, and in one patient, the diagnosis of PHP preceded the onset of weakness by 5 months and in another by 2 years. Serum calcium levels in all five patients were elevated, ranging from 11.2 to 12.8 mg/dL (normal, Results All five patients underwent parathyroid adenoma resection with subsequent normalization of serum calcium and PTH levels. Each patient had progressive weakness resulting in death 1 to 3 years following parathyroidectomy. Conclusion Resection of parathyroid adenomas in patients meeting El Escorial criteria for ALS did not alter the course of ALS. PHP and ALS appear to be coexisting but unrelated disorders.

Inclusion body myositis in twins

Abstract: Sporadic inclusion body myositis (s-IBM) is characterized by late onset of slowly progressive weakness that involves the quadriceps and volar forearm muscles early in the course of the disease. There are hereditary forms of inclusion body myopathy (h-IBM) that histologically resemble s-IBM. The lack of inflammation on biopsy and the different ages at onset and patterns of muscle weakness distinguish s-IBM from h-IBM. We report twin brothers with the typical clinical and histologic features of s-IBM. The occurrence of s-IBM in these twins suggests the possibility of a genetic susceptibility to developing s-IBM.

Microscopic phase separation in La 2 CuO 4 + x induced by the superconducting transition

Abstract: The phase separation (PS) effect in superconducting ${\mathrm{La}}_{2}{\mathrm{CuO}}_{4+x} (xl~0.04)$ single crystals with low oxygen mobility was studied via $\ensuremath{\mu}\mathrm{SR}$ spectroscopy, high-resolution neutron diffraction, and magnetic susceptibility. Despite the fact that all crystals are inside the miscibility gap $(0.01lxl0.06),$ only crystals with a sufficiently large excess oxygen concentration $x=0.04$ show a macroscopic phase separation according to the neutron-diffraction data. However, in all samples a phase transition to an ordered magnetic state was observed by $\ensuremath{\mu}\mathrm{SR}$ spectroscopy concomitantly with the onset of superconductivity. This effect is treated as a microscopic phase separation which is possibly driven by superconductivity.

Magnetic properties of : an exemplary study by muon spin-rotation spectroscopy

Abstract: The results of a muon spin-rotation study of single-crystalline in the paramagnetically and antiferromagnetically (AF) ordered phases are reported. Transverse-field measurements for the paramagnetic phase reveal four components in the signal, distinguished by their different Knight shifts, which can be associated with two crystallographically different sites: a magnetically unique site in the plane near the position , i.e. between two U3 ions, and a site with a threefold symmetry near the centre of a triangle formed by three U1 ions, located in the plane. It appears that the U3 ions are nearly, but not entirely, non-magnetic also in the paramagnetic phase. The temperature dependence of the different Knight shifts follows a Curie-Weiss law but it involves significantly different Curie-Weiss temperatures as compared with the bulk susceptibility, which even show an anisotropy in the hexagonal a-b plane. This does not seem to be a -induced feature but is rather a consequence of selectively monitoring just the magnetic response of the U1 ions. In the AF state below , measurements reveal two different spontaneous internal magnetic fields which can be traced back to the two different sites, thus confirming the non-collinear complex AF structure recently found by neutron scattering.

Muon Spin Relaxation and Nonmagnetic Kondo State in PrInAg_2

Abstract: Muon spin relaxation experiments have been carried out in the Kondo compound PrInAg_2. The zero-field muon relaxation rate is found to be independent of temperature between 0.1 and 10 K, which rules out a magnetic origin (spin freezing or a conventional Kondo effect) for the previously-observed specific heat anomaly at \sim0.5 K. The low-temperature muon relaxation is quantitatively consistent with nuclear magnetism including hyperfine enhancement of the ^{141}Pr nuclear moment. This is strong evidence against a Pr^{3+} electronic magnetic moment, and for the \Gamma_3 crystalline-electric-field-split ground state required for a nonmagnetic route to heavy-electron behavior. The data imply the existence of an exchange interaction between neighboring Pr^{3+} ions of the order of 0.2 K in temperature units, which should be taken into account in a complete theory of a nonmagnetic Kondo effect in PrInAg_2.