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Biomedical subjects

G A Nicholson

Publications and source records attributed to G A Nicholson.

At least 19 recordsLinked to original sources
PubMed1992

Charcot-Marie-Tooth neuropathy type 1A mutation: apparent crossovers with D17S122 are due to a duplication.

A locus for the slow conducting form of Charcot-Marie-Tooth neuropathy (CMT1A) was localised to the proximal short arm of chromosome 17, in band p11.2, distal to D17S58. Linkage studies of CMT1A in 3 large Australian families with the marker loci D17S58, D17S71, and D17S57 suggested the order, pter-CMT1A-D17S71-D17S58-centromere-D17S57. However, the estimate of the recombination fraction between CMT1A and D17S122, also assigned to p11.2, was incompatible with known map distances. The impasse was resolved when the D17S122 genotypes were revised to take into account a dosage effect due to a duplication. After correction of the genotypes, the maximum lod score between CMT1A and D17S122 increased from 0.53 at a recombination fraction of 0.3 to 34.28 at zero recombination. This result emphasizes that genotypes for markers in the p12-p11.2 region should be examined very carefully as ignoring the duplication changes the linkage results dramatically. The fact that no crossovers were found between CMT1A and D17S122 suggests that the duplication may cause the disease phenotype.

Charcot-Marie-Tooth Disease↗
PubMed1991

Undertreatment of glaucoma among black Americans.

BACKGROUND: Cross-sectional studies and those using national data sets estimate that glaucoma-related blindness is between six and eight times more common among black Americans than among whites. Community-based studies have found that glaucoma is four to six times more prevalent among blacks. It is not known why blacks with glaucoma are more likely to become blind than whites with glaucoma. METHODS: To investigate the possibility that undertreatment of glaucoma is an important factor contributing to this higher rate of blindness, we studied the population-based rates of incisional and laser surgery for open-angle glaucoma among blacks and whites in a 5 percent random sample of Medicare claims for 1986 through 1988. RESULTS: For all U.S. census divisions combined, the rate of surgery for glaucoma among black Medicare beneficiaries was 2.2 times higher than the rate among white beneficiaries (95 percent confidence interval, 2.1 to 2.3). We calculated an expected rate of treatment among blacks on the basis of the rate of treatment among whites and the assumption that glaucoma is four times more prevalent among blacks--a conservative estimate. The observed rate of glaucoma surgery among blacks was 45 percent lower than the expected rate we calculated, which may in part account for the excess rate of blindness among blacks. The magnitude of this difference in treatment rates varied from 29 percent in the Middle Atlantic states to 50 percent in the South Atlantic states. CONCLUSIONS: Older black Americans are not receiving potentially sight-saving care for open-angle glaucoma at the same rate as older white Americans.

Black or African American↗
PubMed1991

Penetrance of the hereditary motor and sensory neuropathy Ia mutation: assessment by nerve conduction studies.

The clinical expression of hereditary motor and sensory neuropathy type I (HMSN I) is age-dependent. Autosomal dominant HMSN I is heterogeneous at a molecular level with genes localized on chromosomes 1, 17, and possibly other chromosomes. In order to define accurately the penetrance of a single HMSN I gene mutation, we performed nerve conduction studies in HMSN I families whose genetic defect was linked to chromosome 17 (HMSN Ia). All HMSN Ia subjects tested had slow nerve conduction velocities with a mean median velocity 20 +/- 6 m/sec, which did not change with age. The range of conduction velocities from affected individuals did not overlap those from their clinically normal relatives, indicating complete penetrance of the gene from early childhood. The results indicate that motor nerve conduction studies in children can add additional information for linkage studies and genetic counseling.

Aging↗
PubMed1990

Effect of neural activity on skeletal muscle phosphoproteins.

A number of phosphoproteins were found in the soluble fraction of rat skeletal muscle by two-dimensional polyacrylamide gel electrophoresis (PAGE). The pattern of some of these phosphoproteins differed in fast (extensor digitorum longus, EDL) or slow (soleus) muscles, was dependent on normal innervation, and was altered with denervation. In order to determine if the pattern was maintained by electrical activity or trophic factors, we compared the effect of electrical block by local neural application of tetrodotoxin with the effect of complete nerve section. Both methods produced similar alterations in phosphoproteins, indicating that the pattern is dependent on nerve activity, not trophic factors. Such phosphoproteins are possible mediators of neural activity on gene expression.

Animals↗
PubMed1989

Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17.

Charcot-Marie-Tooth disease Type 1 (CMT) is an inherited neuropathy with known genetic heterogeneity, with at least one autosomal dominant form (CMT Type 1b) linked to the Duffy region of chromosome 1. Autosomal dominant families not demonstrating linkage to the Duffy blood group marker have been designated CMT Type 1a. We report linkage of six CMT Type 1a families to the chromosome 17 markers EW301 (D17S58) and pA10-41 (D17S71) with maximum LOD scores of zeta = 10.49 at theta (maximum recombination fraction) = 0.05 and zeta = 7.36 at theta = 0.06, respectively.

Charcot-Marie-Tooth Disease↗
PubMed1989

The B subunit of coagulation factor XIII is linked to renin and the Duffy blood group to alpha-spectrin on human chromosome 1.

Family linkage studies were used to detect two linkage relationships on human chromosome 1. The B subunit of coagulation factor XIII showed significant linkage to renin with a maximum lod score of 5.071 at a distance of 10 cM. Significant linkage was also shown between the Duffy blood group and alpha-spectrin with linkage results giving a combined lod score of 3.194 at 5 cM.

Blood Group Antigens↗
PubMed1989

Heterogeneity evidence and linkage studies on Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder originally localized to chromosome 1 by linkage to the Duffy blood group. Studies have since shown that the disorder may be heterogeneous, as not all families show this linkage. We tested genetic heterogeneity by the HOMOG computer program in 15 CMT1 pedigrees informative for Duffy. We detected no evidence for heterogeneity in this sample, but when we combined results with previously published lod scores, heterogeneity was statistically significant. Twelve of the 15 families studied did not show linkage to Duffy. We found six of these families to be informative for a chromosome 19 marker, apolipoprotein CII (ApoC2). Despite a previous report showing probable linkage of a non-Duffy-linked CMT1 pedigree to two chromosome 19 markers, we did not detect significant linkage of ApoC2 to CMT1 in these families.

Apolipoprotein C-II↗
PubMed1988

Chromosome I linkage studies in Charcot-Marie-Tooth neuropathy type I.

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder of peripheral nerve. The gene for CMT1 was originally localized to chromosome 1 by linkage to the Duffy blood group, but it has since been shown that not all CMT1 pedigrees show this linkage. We report here the results of linkage studies using five chromosome 1 markers--Duffy (Fy), antithrombin III (AT3), renin (REN), beta-nerve growth factor (NGFB), and salivary amylase (AMY1)--in 16 CMT1 pedigrees. The total lod scores exclude close linkage of CMT1 to any of these markers. However, individual families show probable linkage of CMT1 to Duffy, AT3, and/or AMY1. No linkage was indicated with REN or NGFB. These results indicate the possible location of a CMT1 gene between the AMY1 and AT3 loci at p21 and q23, respectively, on chromosome 1 and support the theory that there is at least one other CMT1 gene.

Charcot-Marie-Tooth Disease↗
PubMed1988

DNA probes in Charcot-Marie-Tooth neuropathy.

Results of Duffy (Fy) linkage confirm genetic heterogeneity in Charcot-Marie-Tooth disease type 1 (CMT1). Of 11 families informative for Fy, four showed probable linkage with CMT1, seven showed-probable non-linkage and two showed definite non-linkage. These results suggest that Fy linked CMT1 may be less common than previously thought. These results combined with those of another DNA probe for the antithrombin III gene confirm that there are at least two gene loci for CMT1, termed 1A and 1B.

Charcot-Marie-Tooth Disease↗
PubMed1987

Regional chromosomal assignment of human renin gene to 1q12----qter and use in linkage studies in Charcot-Marie-Tooth disease.

The gene for renin, previously mapped to human chromosome 1, was further localized to 1q12----qter using human-mouse somatic cell hybrid DNAs. The renin DNA probe used (lambda HR5) could detect a HindIII restriction fragment length polymorphism. When used in studies of 12 informative families, no linkage could be found between the renin gene and Charcot-Marie-Tooth disease. Furthermore, an association of any renin allele with hypertension was not apparent.

Animals↗
PubMed1986

Myasthenia gravis: the problem of a "psychiatric" misdiagnosis.

Patients with myasthenia gravis are commonly misdiagnosed as having a psychiatric disorder; this leads to considerable delay in reaching the correct diagnosis and in instituting appropriate and effective treatment. Patients who are most at risk are those with somatic presentations (limb weakness, fatigue) in contrast to ocular or bulbar presentations. Similarly, those who manifest anger or anxiety traits are more likely to be misdiagnosed.

Anger↗
PubMed1986

Skeletal muscle phosphoproteins: muscle-specific basal and cAMP-dependent phosphoprotein profiles.

To determine whether or not phosphorylation of skeletal muscle proteins is related to functional specialization of individual muscles, we examined the distribution of phosphoproteins in skeletal muscles with different functional properties. Protein phosphorylation was carried out using [gamma-32P]ATP and employing endogenous protein kinases present in skeletal muscle homogenates. Phosphoprotein bands were separated by polyacrylamide gel electrophoresis. We found distinct cAMP-stimulated and basal phosphoprotein patterns in each contraction type; indicating that the phosphoprotein profile is related to functional characteristics. Muscle-specific, cAMP-dependent phosphoproteins may permit coordinate short-term alterations in twitch characteristics of skeletal muscle fibers in response to circulating hormones or other mediators.

Animals↗
PubMed1986

Psychological correlates of myasthenia gravis: a brief report.

Myasthenia gravis patients and matched normal controls were assessed on a range of psychological indices; myasthenic patients had higher scores on trait anxiety and suppression of anger. There were no other significant differences between the groups on psychological symptom measures (anxiety, depression or anger) or other trait measures (anger, suppression of anxiety and suppression of depression). It is concluded that trait anxiety and suppression of anger may predispose to myasthenia gravis.

Adolescent↗
PubMed1985

The creatine kinase reference interval. An assessment of intra- and inter-individual variation.

Serum creatine kinase (CK) values in reference populations generally vary by greater than one order of magnitude. This large range of variation overlaps the range of values found in female carriers of Duchenne muscular dystrophy and limits the clinical usefulness of serum CK testing. In order to examine whether the source of this variation is intrinsic variability of individual CK values, or whether the variation is due to day-to-day variation in each individual's CK activities, we tested 15 female medical students at weekly and 22 female medical students on at least 3 occasions. Each venesection followed a 3-day exercise free interval, according to a standard protocol, designed to minimise the effects of exercise. Each individual tended to have consistent CK activities. The range of variation in the same individuals on different occasions was small (the mean coefficient of variation, CV was 19%). There was a much greater range of serum CK activities between individuals (CV 47%). Even when sporting activities were excluded slightly higher values were found after minor exercise was recorded in the three days prior to venesection. The conclusion that individuals have consistent serum CK activities was supported by the results from a larger population tested under standardised resting conditions on three different occasions which yielded similar frequency distributions on each occasion.

Adult↗
PubMed1985

Variable distributions of serum creatine kinase reference values. Relationship to exercise activity.

Although the effect of exercise on serum creatine kinase (CK: EC 2.7.3.2) activity is well known, no standard protocol for blood collection conditions has been developed. Variable frequency distributions of CK activities have been reported for reference range samples from different laboratories and have been attributed to laboratory differences. In this study the frequency distributions of creatine kinase activities (CK: EC 2.7.3.2) in serum samples obtained from the same groups of volunteers varied from a normal Gaussian distribution, to skewed distributions, on different occasions. In one collection extremely high CK values followed the performance of an eccentric exercise step test 5-8 days previously. In 2 students serum CK activities had not returned to resting values 12 and 15 days later. Peak serum CK values occurred within 24 h of other types of exercise. Serum CK frequency distributions in blood samples obtained from a group of nurses was skewed, whereas the distribution in mothers of school children was Gaussian. When repeat samples were obtained from the nurses after instruction to avoid exercise, the distribution became Gaussian. In view of the increasing levels of physical activity in the community, a standard protocol for serum CK analysis is required, in which exercise activity over the previous three weeks should be documented. Test subjects should be counselled to avoid unusual eccentric exercise and sampling should include 3 tests at least 1 week apart.

Adolescent↗