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Biomedical subjects

W A Mitchell

Publications and source records attributed to W A Mitchell.

14 recordsLinked to original sources
PubMed2001

Turkish variant late infantile neuronal ceroid lipofuscinosis (CLN7) may be allelic to CLN8.

One variant form of late infantile neuronal ceroid lipofuscinosis (LINCL) is found predominantly within the Turkish population (CLN7). Exclusion mapping showed that CLN7 was not an allelic variant of known NCL loci (CLN1, CLN2, CLN3, CLN5 or CLN6). Using the method of homozygosity mapping, a genome-wide search was undertaken and a total of 358 microsatellite markers were typed at an average distance of about 10 cM. A region of shared homozygosity was identified on chromosome 8p23. This telomeric region contained the recently identified CLN8 gene. A missense mutation in CLN8 causes progressive epilepsy with mental retardation (EPMR) or Northern epilepsy, which has so far been reported only from Finland and is now classified as an NCL. The mouse model mnd has been shown to carry a 1 bp insertion in the orthologous Cln8 gene. Statistically significant evidence for linkage was obtained in this region, with LOD scores > 3, assuming either homogeneity or heterogeneity. Flanking recombinants defined a critical region of 14 cM between D8S504 and D8S1458 which encompasses CLN8. This suggests that Turkish variant LINCL, despite having an earlier onset and more severe phenotype, may be an allelic variant of Northern epilepsy. However mutation analysis has not so far identified a disease causing mutation within the coding or non-coding exons of CLN8 in the families. The Turkish variant LINCL disease-causing mutation remains to be delineated.

Alleles↗
PubMed2001

Genomic structure of three CLN3-like genes in Caenorhabditis elegans.

The genome of Caenorhabditis elegans is predicted to carry three genes similar to CLN3, the gene underlying juvenile neuronal ceroid lipofuscinosis. All three genes are transcribed and the genomic structure has been determined. The number and position of exons for two of the genes differ from that predicted from the genomic sequence, but no discrepancies with the genomic nucleotide sequence were found. Gene F07B10.1 (cln-3.1) is predicted to have 7 exons and to encode a protein of 424 amino acids. Gene C01G8.2 (cln-3.2) has 9 exons and encodes a protein of 435 amino acids. Gene ZC190.1 (cln-3.3) is predicted to have 9 exons and to encode a protein of 416 amino acids.

Animals↗
PubMed1999

A new locus for variant late infantile neuronal ceroid lipofuscinosis-CLN7.

To date two genes are known to be involved in variant LINCL, CLN5 and CLN6, which map to chromosomes 13q21 and 15q21-23. A subset of Turkish families with a variant phenotype has been identified. Affected individuals have curvilinear bodies and fingerprint profiles on EM but are recombinant at CLN5 and CLN6. These families appear to represent a new locus. Homozygosity mapping is being used to map this locus, which has been designated CLN7.

DNA Mutational Analysis↗
PubMed1993

The effect of digitonin and altered thyroid status on palmitic acid oxidation by isolated rat liver mitochondria.

The effect of altered thyroid status and food-deprivation on palmitic acid oxidation in isolated rat liver mitochondria was studied in the absence and presence of digitonin. Mitochondria prepared from triiodothyronine-treated (hyperthyroid) and food-deprived rats metabolized palmitic acid at the same rate as the untreated controls (euthyroid). Mitochondria prepared from thyroidectomized (hypothyroid) rats metabolized palmitic acid at a rate lower than was that seen with mitochondria from euthyroid controls in either the fed or fasted state. Fasting had no effect on palmitic acid oxidation by mitochondria prepared from euthyroid rats but diminished the rates seen in both hyper- and hypothyroid states. Digitonin (0.04 mg/mg mitochondrial protein) increased the sensitivity of the rate of fatty acid oxidation to inhibition by alpha-bromopalmitic acid. The addition of digitonin to the incubation mixture resulted in two-fold increases in the rate of palmitic acid oxidation in all states. This study shows that the limitations imposed by hypothyroidism on fatty acid oxidation in intact liver are preserved in isolated mitochondria.

Animals↗
PubMed1980

Coronary arteriograms and myocardial scintigrams in the electrocardiographic syndrome of septal fibrosis.

Coronary artery disease (CAD) and myocardial perfusion were assessed by arteriograms and scintigrams (Technetium-99 microspheres alone or combined with Iodine-131 albumin macroaggregates) in 178 angina pectoris patients with and without the electrocardiographic (ECG) syndrome of septal fibrosis and with greater than or equal to 70% obstruction in one or more coronary arteries. The ECGs of 96 patients without angiographic evidence of obstructive CAD were also examined for the ECG syndrome of septal fibrosis. Patients with the ECG syndrome of septal fibrosis have significantly higher incidences of positive exercise stress test, of greater than or equal to 70% narrowing of the proximal left anterior descending (LAD) artery, of severe proximal LAD disease, and of more extensive left ventricular hypoperfusion than patients without the ECG syndrome. The fact that only 4% of patients without obstructive CAD have the ECG syndrome of septal fibrosis indicates the usefulness of the syndrome in identifying a subset of angina pectoris patients with advanced CAD of the proximal LAD and diffuse left ventricular hypoperfusion.

Angina Pectoris↗
PubMed1980

Clinical and pathologic features of obstructive disease in the predominant right and left coronary circulations in man.

The clinical features and the location and severity of obstructive coronary artery disease are contrasted in 98 patients with predominant left and 99 patients with predominant right coronary circulations. A significantly higher incidence of ventricular conduction disturbances and a greater incidence and severity of obstructive coronary artery disease (greater than or equal to 70% cross-sectional narrowing in the proximal left anterior descending, circumflex and right coronary arteries and their major branches) distinguish the predominant left from the predominant right coronary circulation. The results suggest an anatomically disadvantaged status for the predominant left compared with the predominant right coronary circulations with respect to ventricular conduction disturbances and to coronary atherogenesis in man.

Arterial Occlusive Diseases↗
PubMedDate not supplied

Chondral fractures of the knee. Cause for confusion.

Knee pain in the athlete can pose difficulty in diagnosis. At the United States Military Academy at West Point we have had occasion to see a group of patients presenting with meniscal symptoms of locking, catching, giving way, and joint line tenderness who, on arthroscopic examination, have chondral fractures of the medial or lateral femoral condyle. These individuals have undergone arthroscopy and debridement of the chondral defect. Both retrospectively and prospectively we have been unable to find any defects on radiographs and there appears to be purely cartilaginous involvement. These individuals appear to have a relatively poor prognosis for recovery after arthroscopy. Treatment has been a standard course of range of motion exercises, strengthening, and antiinflammatory medications. However, the mean rehabilitation time has been almost triple the time associated with a routine meniscal injury. We feel that it is important to discuss the chondral fracture so that the orthopaedic surgeon can be aware of this possibility in the differential diagnosis of knee pain in the athlete.

Adolescent↗
PubMedDate not supplied

Agility training following anterior cruciate ligament reconstruction.

The treatment program after anterior cruciate ligament (ACL) injury or reconstruction at the United States Military Academy embraces the four cornerstones of rehabilitation--strength, aerobic fitness, coordination, and confidence. It is divided into six phases--presurgery, to prepare the patient for postoperative rehabilitation; postoperative (or postinjury), to allow healing and to prevent thrombosis and muscle atrophy; early healing, to maintain muscle tone and joint motion in a protective device; late healing (water stage), to begin proprioceptive and agility training while regaining joint motion; healed (land stage), to gain greater agility and confidence in controlled situations; competition, to demonstrate if the rehabilitation program has been successful. This paper concentrates on the criteria for advancing from the water phase to the land phase and then to competition. The patient reverts to the preceding phase if pain or swelling is apparent. Full participation in competition is not permitted unless the patient masters all phases and can compete in athletics without fear of reinjury.

Athletic Injuries↗