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Biomedical subjects

C A Garcia

Publications and source records attributed to C A Garcia.

At least 19 recordsLinked to original sources
PubMed1992

The gene for the peripheral myelin protein PMP-22 is a candidate for Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is an autosomal dominant peripheral neuropathy associated with a large DNA duplication on the short arm of human chromosome 17. The trembler (Tr) mouse serves as a model for CMT1A because of phenotypic similarities and because the Tr locus maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17. Recently, the peripheral myelin gene Pmp-22 was found to carry a point mutation in Tr mice. We have isolated cDNA and genomic clones for human PMP-22. The gene maps to human chromosome 17p11.2-17p12, is expressed at high levels in peripheral nervous tissue and is duplicated, but not disrupted, in CMT1A patients. Thus, we suggest that a gene dosage effect involving PMP-22 is at least partially responsible for the demyelinating neuropathy seen in CMT1A.

Amino Acid Sequence↗
PubMed1992

Comparison of retinal photocoagulation using pulsed frequency-doubled neodymium-YAG and argon green laser.

The photocoagulation effects on retinal and choroidal tissue of the argon green and pulsed frequency-doubled neodymium-YAG lasers were examined in rabbit eyes. In contrast to the continuous wave output of the argon green laser, the pulsed frequency-doubled neodymium-YAG laser produces a series of 1 microsecond pulses emitted at a repetition rate of 10 kHz. The high repetition rate results in pulse averaging, allowing relatively low peak powers to be used while producing average powers capable of thermal tissue effects. Photocoagulation lesions in the rabbit retina were placed in pairs using each of the lasers. Light microscopic comparison of the argon and neodymium-YAG burns revealed morphologically similar lesions for up to 14 days after photocoagulation, with damage predominantly at the level of the retinal pigment epithelium and outer retina. The high repetition rate, pulsed frequency-doubled neodymium-YAG laser produced thermal tissue effects similar to the continuous wave argon green laser.

Animals↗
PubMed1992

Molecular genetics and neuropathology of Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-Tooth (CMT) syndrome describes a genetically and clinically heterogeneous group of polyneuropathies. Electrophysiologically, at least two types of CMT can be distinguished; CMT1 which has decreased nerve conduction velocities (NCV) and CMT2 which has normal or near normal NCV with decreased amplitudes. For CMT1, three gene loci (on chromosomes 1, 17 and the X chromosome) have been mapped. The locus on chromosome 17, CMT type 1A (CMT1A), is responsible for the most common form of CMT which has recently been shown to be associated with a large DNA duplication. Recent data demonstrates that the CMT1A phenotype results from an inherited DNA rearrangement and a gene dosage effect. The trembler (Tr) and allelic tremblerJ (TrJ) mice have been proposed as animal models for CMT. Tr has similar electrophysiological and neuropathological features to CMT1 patients and maps to mouse chromosome 11 in a region of conserved synteny with human chromosome 17p. Tr and TrJ have recently been shown to have different point mutations in regions encoding putative transmembrane domains of the myelin specific protein PMP-22. The human peripheral nerve-specific PMP-22 gene maps within the CMT1A duplication. PMP-22 is thus a candidate gene for CMT1A. This paper describes the molecular genetics of CMT1A and sural nerve pathology in CMT1A patients with the CMT1A duplication.

Adult↗
PubMed1992

Familial inclusion body myositis: evidence for autosomal dominant inheritance.

We report a kindred manifesting clinical features and muscle biopsy findings of inclusion body myositis (IBM). In this family, multiple members were affected in two generations with direct male-to-male and female-to-male transmission. This is the first reported instance of autosomal dominant inheritance in IBM, which usually occurs sporadically or, rarely, may be transmitted as an autosomal recessive disorder.

Adult↗
PubMed1992

Electrode comparison in pattern electroretinography.

In recent years, there has been great interest in recording the pattern electroretinogram (PERG) in glaucomatous and diabetic populations. The Dawson, Trick, and Litzkow thread electrode (DTLTE) and the gold foil electrode (GFE), commonly used for recording PERGs, were compared for variations in amplitude of response, test-retest variability, and patient comfort. Two study centers collected data on a total of 32 normal subjects. The subjects from the London center showed a slight (but not significant) preference for the DTLTE, and the Houston subjects also found the DTLTE to be significantly more comfortable (chi-square = 39, P less than 0.001). In both study groups, the GFE was found to produce a statistically larger amplitude of response than that obtained with the DTLTE. Significant differences were found regardless of the slow (transient, 3.1 Hz; F = 6.24; P = 0.0192) or fast (steady state, 8.3 Hz; F = 18.38; P = 0.0001) stimulus-presentation rate. Larger differences between the two electrodes occurred under steady-state conditions. Although there is no consensus as to the optimum recording conditions to obtain the subtle PERG, it appears the the GFE records larger responses than the DTLTE. However, test-retest data confirmed that the GFE records twice the amplitude of the DTLTE, and it also produced twice the variability (average percent difference over time for GFE, 15%; for DTLTE, 8%).

Adolescent↗
PubMed1991

Discordance of muscular dystrophy in monozygotic female twins: evidence supporting asymmetric splitting of the inner cell mass in a manifesting carrier of Duchenne dystrophy.

In 1990, Richards et al. reported dramatically skewed lyonization in a set of female monozygotic twins heterozygous for Duchenne muscular dystrophy (DMD). The skewed inactivation pattern was symmetrical in opposite directions, one twin being affected with DMD, the other one being normal. Here, we report an additional set of female monozygotic twins heterozygous for a mutation at the dystrophin locus. Similarly, one shows a manifesting carrier phenotype while one is normal. However, unlike the previous report, we find a skewed X inactivation pattern only in the affected twin, while the normal twin showed a random X inactivation pattern. Our results lend considerable experimental support for the models of twinning and X inactivation recently outlined by Nance in 1990, in that these twins probably represent asymmetric splitting of the inner cell mass (ICM): The affected twin likely arose when a small proportion of the ICM split off after lyonization had occurred. In this situation, the original ICM could give rise to the normal twin with random lyonization, while the newly split cells would experience catch-up growth and lead to the affected twin. Genetic studies of this family showed that the specific dystrophin gene mutation was an exon duplication that arose sporadically in the paternally derived X chromosome.

Adult↗
PubMed1991

DNA duplication associated with Charcot-Marie-Tooth disease type 1A.

Charcot-Marie-tooth disease type 1A (CMT1A) was localized by genetic mapping to a 3 cM interval on human chromosome 17p. DNA markers within this interval revealed a duplication that is completely linked and associated with CMT1A. The duplication was demonstrated in affected individuals by the presence of three alleles at a highly polymorphic locus, by dosage differences at RFLP alleles, and by two-color fluorescence in situ hybridization. Pulsed-field gel electrophoresis of genomic DNA from patients of different ethnic origins showed a novel SacII fragment of 500 kb associated with CMT1A. A severely affected CMT1A offspring from a mating between two affected individuals was demonstrated to have this duplication present on each chromosome 17. We have demonstrated that failure to recognize the molecular duplication can lead to misinterpretation of marker genotypes for affected individuals, identification of false recombinants, and incorrect localization of the disease locus.

Animals↗
PubMed1991

Is the carboxyl-terminus of dystrophin required for membrane association? A novel, severe case of Duchenne muscular dystrophy.

Duchenne muscular dystrophy is a lethal X-linked recessive disorder caused by the deficiency of a component of the muscle fiber membrane cytoskeleton called dystrophin. Becker muscular dystrophy, a clinically milder disorder, results from dystrophin abnormalities rather than deficiency. We identified the first patient who is clearly an exception to these established clinical and biochemical correlates. The patient described clinically had particularly severe Duchenne dystrophy. Biochemically, his muscle contained substantial amounts of abnormal dystrophin (Becker-like). Characterization of the dystrophin protein and gene revealed a unique intragenic gene deletion resulting in a dystrophin protein missing the carboxyl-terminal domain. This patient's dystrophin seemed to have a deleterious "dominant" effect on his muscle: The presence of this abnormal protein was more damaging to the myofibers than the absence of dystrophin would have been. This patient challenges the current hypothesis that dystrophin associates with the plasma membrane solely via its carboxyl-terminus, yet supports the hypothesis that an intact carboxyl-terminus is crucial for correct dystrophin function.

Chromosome Deletion↗
PubMed1990

The pattern electroretinogram in diabetes.

In 27 normal subjects and 64 insulin-dependent diabetic patients, we evaluated the pattern electroretinogram, which may reflect the neural activity of the spatially sensitive retinal ganglion cells. The amplitude of the pattern electroretinogram was reduced in diabetic patients who had no observable retinal changes. The amplitude was further reduced with increasing retinopathy. The pattern electroretinogram amplitude change was a more sensitive indicator of retinal change among the diabetic subpopulations than the statistically significant changes in latency. A significant correlation between pattern electroretinogram amplitude and the duration of diabetes were found in diabetic patients with either no observable retinopathy or minimal background retinopathy. The pattern electroretinogram may be useful as a quantitative, dependent variable to establish and monitor short-term metabolic and physiologic changes in diabetic patients.

Adolescent↗
PubMed1990

Peripheral neuropathy associated with eosinophilia-myalgia syndrome.

In 1989, the Centers for Disease Control recognized the existence of an epidemic illness characterized by myalgia and eosinophilia in individuals taking preparations containing L-tryptophan. We evaluated 3 patients with eosinophilia-myalgia syndrome who presented with subacute progressive neuropathies. The neuropathies were predominantly motor and maximal in the lower extremities. Two patients were confined to a wheelchair and one was ventilator-dependent and bedridden. Sensory loss predominantly involved small fiber modalities. Electrophysiological studies showed multifocal marked conduction slowing and conduction block indicating segmental demyelination, with associated axonal degeneration that was accentuated distally. Examination of sural nerve biopsy specimens demonstrated axonal degeneration in all 3 patients and perivascular infiltrates in 2. Levels of quinolinic acid, a neurotoxic metabolite of L-tryptophan, were elevated in the cerebrospinal fluid in the 2 patients in whom it was measured. The cause of the neuropathy is unknown but may include immune mechanisms or toxicity of eosinophils, L-tryptophan, its metabolic products, or contaminants within L-tryptophan preparations.

Adult↗
PubMed1990

Differentiation of Naegleria fowleri from Acanthamoeba species by using monoclonal antibodies and flow cytometry.

Monoclonal antibodies to Naegleria fowleri and Acanthamoeba polyphaga were analyzed by enzyme-linked immunosorbent assay, indirect immunofluorescence microscopy, and fluorescence flow cytometry to assess specificity and cross-reactivity with axenically cultured N. fowleri and Acanthamoeba spp. Four monoclonal antibodies to N. fowleri were specific for N. fowleri and had no reactivity to A. polyphaga. Similarly, four monoclonal antibodies to A. polyphaga did not react with N. fowleri. Two of the four monoclonal antibodies to A. polyphaga did not react with other Acanthamoeba spp. tested, while two of the antibodies demonstrated a high degree of cross-reactivity with a putative Acanthamoeba castellanii strain by immunofluorescence microscopy; this was confirmed by fluorescence flow cytometry for one of the antibodies. These monoclonal antibodies were used to identify Acanthamoeba trophozoites in infected brain sections of a patient who died of suspected Acanthamoeba-caused granulomatous amoebic encephalitis, demonstrating potential utility in the direct identification of N. fowleri and Acanthamoeba spp. in clinical specimens.

Acanthamoeba↗
PubMed1988

Intrafamilial variability in fucosidosis.

Two families with five patients affected with fucosidosis are described. Within each family, both type I and type II fucosidosis are present. This suggests that environmental factors or "modifying genes" different from the fucosidase structural gene contribute to the phenotype of a fucosidosis patient.

Adult↗
PubMed1987

ECG abnormalities in myoglobinuria: review of the literature.

Reports of electrocardiographic abnormalities in association with myoglobinuria have been sparse and have included conduction disturbances, ST segment shifts, and T-wave changes. In many instances, these changes were noted in patients with underlying heart disease. We report a case of a 34-year-old woman with ST segment depression and T-wave inversion in the inferolateral leads during the acute episode of myoglobinuria. There was no demonstrable underlying heart disease, and there was parallel resolution of these ECG changes with myoglobinuria. We conclude that these ECG changes were produced by cardiac muscle involvement in a manner similar to that observed in skeletal muscle in myoglobinuria.

Adult↗
PubMed1987

Tumors of the brachial plexus.

Over a 17-year period, 56 patients with 57 tumors involving the brachial plexus were operated upon. The 40 neural sheath tumors included 26 neurofibromas, 8 schwannomas, 4 malignant neural sheath tumors, 1 fibrosarcoma, and 1 meningioma. Nine of the neurofibromas were associated with von Recklinghausen's disease (VRD), and 2 others were what was termed regionalized neurofibromatosis characterized by involvement of one limb with extension along the course of one or more plexus elements. Seventeen tumors were not of neural sheath origin; 7 were benign and 10 were metastatic malignant tumors compressing or invading the plexus. Benign neurofibromas and malignant sheath tumors almost always presented with pain or functional neural deficit, whereas schwannomas often presented with a palpable mass as their only initial symptom. Patients with solitary neurofibromas were significantly older, often female, and more likely to have tumor on the right side than patients with schwannomas, malignant neural sheath tumors, or neurofibromas associated with VRD. Solitary neurofibromas could often be totally resected without added deficit by sacrificing fascicles entering and leaving tumor that were determined to be "nonfunctional" by intraoperative nerve action potential recordings. Resection of neurofibromas associated with VRD sometimes but not always resulted in significant loss. Operation is nonetheless recommended, especially when malignancy is suspected because of rapidly increasing size, when severe pain or neural deficit is present, or when compression of adjacent plexus elements is a concern. Schwannomas and benign non-neural sheath tumors can usually be extirpated without damage to plexus elements. Forequarter amputation is advised for malignant intrinsic tumors involving distal plexus elements even though gross total resection seems feasible.

Adult↗