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Biomedical subjects

J Galt

Publications and source records attributed to J Galt.

17 recordsLinked to original sources
PubMed1998

Exon organization, coding sequence, physical mapping, and polymorphic intragenic markers for the human neuronal sodium channel gene SCN8A.

The voltage-gated sodium channel SCN8A is associated with inherited neurological disorders in the mouse that include ataxia, dystonia, severe muscle weakness, and paralysis. We report the complete coding sequence and exon organization of the human SCN8A gene. The predicted 1980 amino acid residues are distributed among 28 exons, including two pairs of alternatively spliced exons. The SCN8A protein is evolutionarily conserved, with 98.5% amino acid sequence identity between human and mouse. Consensus sites for phosphorylation of serine/threonine and tyrosine residues are present in cyoplasmic loop domains. The polymorphic (CA)n microsatellite marker D12S2211, with PIC = 0.68, was isolated from intron 10C of SCN8A. Single nucleotide polymorphisms in intron 19 and exon 22 were also identified. We localized SCN8A to chromosome band 12q13.1 by physical mapping on a YAC contig. The cDNA clone CSC-1 was reported by others to be a cardiac-specific sodium channel, but sequence comparison demonstrates that it is derived from exon 24 of human SCN8A. The genetic information described here will be useful in evaluating SCN8A as a candidate gene for human neurological disease.

Alternative Splicing↗
PubMed1997

Multicenter trial validation of a camera-based method to measure Tc-99m mercaptoacetyltriglycine, or Tc-99m MAG3, clearance.

PURPOSE: To evaluate an improved camera-based method for calculating the clearance of technetium-99m mercaptoacetyltriglycine (MAG3) in a multicenter trial. MATERIALS AND METHODS: Tc-99m MAG3 scintigraphy was performed in 49 patients at three sites in the United States and Canada. The percentage of the injected dose of Tc-99m MAG3 in the kidney at 1-2, 1.0-2.5, and 2-3 minutes after injection was correlated with the plasma-based Tc-99m MAG3 clearances. The data were combined with the results obtained in 20 additional patients in a previously published pilot study. RESULTS: Regression models correlating the plasma-based Tc-99m MAG3 clearance with the percentage uptake in the kidney for each time interval were developed; there was no statistically significant difference among sites in the regression equations. Correction for body surface area statistically significantly (P < .005) improved the correlation coefficient for each time interval. For the 1.0-2.5-minute interval, the body surface area-corrected correlation coefficient for the four combined sites was .87, and it improved to .93 when one outlier was omitted from the analysis. Similar results were obtained with the other time intervals. Independent processing by two observers showed no clinically important differences in the percentage dose in the kidney or in relative function. CONCLUSION: An improved camera-based method to calculate the clearance of Tc-99m MAG3 was validated in a multicenter trial.

Adolescent↗
PubMed1995

Insertional mutation of the motor endplate disease (med) locus on mouse chromosome 15.

Homozygous transgenic mice from line A4 have an early-onset progressive neuromuscular disorder characterized by paralysis of the rear limbs, muscle atrophy, and lethality by 4 weeks of age. The transgene insertion site was mapped to distal chromosome 15 close to the locus motor endplate disease (med). The sequence of mouse DNA flanking the insertion site junctions was determined. A small (< 20 kb) deletion was detected at the insertion site, with no evidence of additional rearrangement of the chromosomal DNA. Noncomplementation of the transgene-induced mutation and med was demonstrated in a cross with medJ/+mice. The new allele is designated medTgNA4Bs (medtg). The homologous human locus MED was assigned to chromosome 12. Synaptotagmin 1 and contactin 1 were eliminated as candidate genes for the med mutation. The transgene-induced allele provides molecular access to the med gene, whose function is required for synaptic transmission at the neuromuscular junction and long-term survival of cerebellar Purkinje cells.

Animals↗
PubMed1995

Mutation of a new sodium channel gene, Scn8a, in the mouse mutant 'motor endplate disease'.

The mouse neurological mutant 'motor endplate disease' (med) is characterized by early onset progressive paralysis of the hind limbs, severe muscle atrophy, degeneration of Purkinje cells and juvenile lethality. We have isolated a voltage-gated sodium channel gene, Scn8a, from the flanking region of a transgene-induced allele of med. Scn8a is expressed in brain and spinal cord but not in skeletal muscle or heart, and encodes a predicted protein of 1,732 amino acids. An intragenic deletion at the transgene insertion site results in loss of expression. Scn8a is closely related to other sodium channel alpha subunits, with greatest similarity to a brain transcript from the pufferfish Fugu rubripes. The human homologue, SCN8A, maps to chromosome 12q13 and is a candidate gene for inherited neurodegenerative disease.

Amino Acid Sequence↗
PubMed1995

Measuring technetium-99m-MAG3 clearance with an improved camera-based method.

UNLABELLED: Because commercially available camera-based methods are not optimized, they fail to account for dose infiltration, table attenuation and correspondence between time of injection and starting the camera. We have developed a more optimized technique to calculate camera-based clearances and applied this technique in the design of a camera-based clearance method for 99mTc-MAG3. METHODS: Technetium-99m-MAG3 scintigraphy was performed in 20 patients who had varying degrees of renal function. Data were acquired posteriorly in supine patients at 2 sec/frame for 24 frames, 15 sec/frame for 16 frames and 30 sec/frame for 40 frames. Background correction was performed using an automated elliptical region of interest. Renal depth was estimated using improved regression equations and an empirically determined attenuation coefficient derived from phantom studies. Corrections were made for table attenuation and time discrepancies between dose injection and starting the camera. The percent injected dose in the kidney at 1-2, 1-2.5 and 2-3 min postinjection and the percent injected dose at those time periods corrected for body surface area were correlated with MAG3 clearance based on a single injection, two-compartment model. RESULTS: There was high correlation between the percent injected dose in the kidney at all three time periods and the multisample clearance. Correcting for body surface areas significantly improved the correlation coefficients. Consequently, regression equations were developed to predict multisample clearance based on percent dose and body surface area. CONCLUSION: The optimization features described in this method should improve precision when sequential studies are conducted in the same patient.

Adult↗
PubMed1990

Technical aspects of myocardial SPECT imaging with technetium-99m sestamibi.

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Graphics↗
PubMed1989

Isolation of chromosome-21-specific DNA probes and their use in the analysis of nondisjunction in Down syndrome.

Thirteen single-copy, chromosome-21-specific DNA probes were isolated from a recombinant library made from flow-sorted chromosome 21 DNA and regionally mapped using a panel of somatic cell hybrids. Five probes mapped in the 21q21-q22.1 region, six to the 21q22.1-qter region, and one to each of the regions 21q22.1-q22.2 and 21q22.3. Two of these probes, one of which maps in the critical region for Down syndrome, have recently been shown to be expressed at high levels in Down syndrome brain tissue (Stefani et al. 1988). Following preliminary screening for restriction fragment length polymorphisms (RFLPs), five polymorphisms were discovered with four of the chromosome 21 DNA probes. A frequent MspI polymorphism detected by one of the probes was used in conjunction with four previously described polymorphic chromosome 21 probes to analyse the origin of nondisjunction in 33 families with a child or fetus with trisomy 21. The parental origin of the additional chromosome 21 was determined in 12 cases: in 9 (75%) of these it was derived from the mother and in the other 3 cases (25%) it was of paternal origin. Cytogenetic analysis of Q-banding heteromorphisms was informative in three of five families tested, and in each case the RFLP results were confirmed. The meiotic stage of nondisjunction was defined with confidence in five families, the results being obtained with pericentromeric RFLP or cytogenetic markers. Recombination between two nondisjoined chromosomes was demonstrated in one family and is consistent with the view that a lack of recombination between chromosome 21 homologues or failure of their conjunction is not the invariable cause of trisomy 21.

Chromosome Banding↗
PubMed1988

Expression of chromosome 21 specific sequences in normal and Down's syndrome tissues.

Using RNA isolated from age and sex matched normal and Down's Syndrome foetal liver and brain tissues, Northern blots were prepared and probed with 4 chromosome 21 specific sequences. The results show that no consistent pattern of expression emerges when Down's Syndrome tissue is compared with normal tissue but the results are very different from the 3/2 ratio of expression which may be expected. Two sequences 21.3 and 26C show only minor differences in expression in trisomy 21 liver samples but significant changes in their expression pattern when normal and Down's Syndrome brain samples are compared. The other sequences, JG77 and JG90 show a 5 fold higher degree of expression in Down's brain but when liver samples are compared one of these sequences shows equal levels of expression in normal and Down's Syndrome samples and the other shows a decrease in expression level in Down's Syndrome samples.

Animals↗
PubMed1985

Cloned DNA probes regionally mapped to human chromosome 21 and their use in determining the origin of nondisjunction.

A number of unique sequence recombinant DNA clones were isolated from a recombinant DNA library constructed from DNA enriched for chromosome 21 by flow sorting. Of these, five were mapped to chromosome 21 using a somatic cell hybrid. Regional mapping of these probes and of a probe previously assigned to chromosome 21, was carried out with the aid of chromosome 21 rearrangements using both chromosome sorting and a somatic cell hybrid. Three probes were shown to be located on either side of the breakpoint 21q21.2. Two of the probes were shown to identify restriction fragment length polymorphisms (RFLPs) with high rare-allele frequencies (0.46 and 0.43). A Bgl II RFLP revealed the parental origin of non-disjunction in three of ten families with Down's syndrome.

Cell Line↗