Biomedical subjects

C A Williams

Publications and source records attributed to C A Williams.

At least 55 records · Page 3Linked to original sources

PubMed1998

Genetic counseling in Angelman syndrome: the challenges of multiple causes.

The causal heterogeneity of Angelman syndrome (AS) makes providing information regarding recurrence risk both important and challenging, and may have a dramatic impact on reproductive decision-making for the nuclear and extended family. Most cases of AS result from typical large de novo deletions of 15q11-q13, and are expected to have a low (<1%) risk of recurrence. AS due to paternal uniparental disomy (UPD), which occurs in the absence of a parental translocation, is likewise expected to have a <1% risk of recurrence. Parental transmission of a structurally or functionally unbalanced chromosome complement can lead to 15q11-q13 deletions or to UPD and will result in case-specific recurrence risks. In instances where there is no identifiable large deletion or UPD, the risk for recurrence may be as high as 50% as the result of either a maternally inherited imprinting center (IC) mutation or a ubiquitin-protein ligase (UBE3A) gene mutation. Individuals with AS who have none of the above abnormalities comprise a significant proportion of cases, and some may be at a 50% recurrence risk. Misdiagnoses, as well, can be represented in this group. In light of the many conditions which are clinically similar to AS, it is essential to address the possibility of diagnostic uncertainty and potential misdiagnosis prior to the provision of genetic counseling. Summaries of the different causal classes of AS as an algorithm for determination of recurrence risks are presented.

Angelman Syndrome↗

PubMed1998

Release of nociceptin-like substances from the rat spinal cord dorsal horn.

Release of nociceptin-like substances from the dorsal horn of rat spinal cords in situ was measured by the immobilized-antibody microprobe technique. Spinal cords removed from anesthetized 4-6 week-old rats were superfused with oxygenated Krebs solution at room temperature (21+/-1 degrees C). Glass microelectrodes, coated with antibodies to nociceptin, were inserted into the dorsal horn of the lumbar spinal cord (1.9 mm lateral to the midline to a depth 2.5 mm below the surface of the cord) for 15 min periods before, during and after electrical stimulation applied to the dorsal root entry zone of the same segment. There was a basal release of immunoreactive nociceptin-like substance (irNC) from the dorsal horns during the pre-stimulation period. A significant increase in irNC release was detected during the period of electrical stimulation and this increase was maintained for at least 15 min following the cessation of electrical stimulation. These results provide the first evidence on the release of irNC, albeit non-quantitative, from the in situ rat spinal cord dorsal horn and an enhanced release upon electrical stimulation.

Animals↗

PubMed1998

A novel mutation (V191G) in a German-British type 1 Gaucher disease patient. Mutations in brief no. 131. Online.

Gaucher disease results from mutations in the glucocerebrosidase gene located on human chromosome 1q21. Three clinical forms of Gaucher disease have been described: type 1, nonneuropathic; type 2, acute neuropathic; and type 3, subacute neuropathic. We have identified a novel mutation in a German-British patient with type 1 Gaucher disease which results in V191G of the glucocerebrosidase polypeptide. Because the mutation abolishes a HphI cleavage site, its presence was confirmed by HphI RFLP analysis of PCR-amplified genomic DNA. In the second allele of the patient, the mutation identified was g.5841A G(N370S). Sequence analysis of the remainder of the coding region of the gene as well as the exon-intron boundaries showed identity to normal controls. Because mutation N370S has so far been found only in type 1 Gaucher disease and postulated to result in mild clinical presentation, and since the clinical course of this patient has been relatively mild with minimal skeletal involvement, we speculate that the V191G/N370S genotype may also result in good prognosis.

Chromosomes, Human, Pair 1↗

PubMed1998

Bias and limits of agreement between hydrodensitometry, bioelectrical impedance and skinfold calipers measures of percentage body fat.

Previous research has often used correlations as a statistical method to show agreement; however, this is not a valid use of the statistic. The purpose of this study was to investigate the bias and limits of agreement for three methods of estimating percentage body fat for 117 male and 114 female university athletes: hydrodensitometry (HYD), bioelectrical impedance (BIA) and skinfold calipers (SKF). The mean (SD) percentage body fat for males as assessed by HYD, BIA and SKF methods, respectively, were 13.2 (3.3)%, 14.1, (3.3)% and 13.0 (3.2)%. Female body fat measurements were 22.5 (3.9)%, 23.7 (4.3)% and 23.8 (4.2)%, respectively. Pearson product moment correlations for male and female body fat percentages between the three methods were high, ranging from 0.81 to 0.86 (P < 0.05). However, compared to the criterion measure of body fat percentage (HYD), the magnitude of agreement BIA and SKF revealed a different pattern. The mean absolute difference between HYD and BIA measurements of body fat for males was -0.8 (2.0)% fat, and between HYD and SKF was it was 0.2 (1.7)% fat. The mean absolute difference for females between HYD and BIA was -1.2 (2.5)%; for HYD and SKF it was -1.4 (2.2)%. Compared to the HYD measures for males and females, the BIA and SKF measures were as much as a 3.8% underestimation and a 6.2% overestimation of body fat. This study provides evidence that the strength of a correlation does not indicate agreement between two methods. In future, reliability and validity studies should examine the absolute differences between two variables and calculate limits of agreement around which a practitioner can appreciate the precision of the methodologies.

Adipose Tissue↗

PubMed1998

Characterization of turkey spermiophages with regard to traits common to macrophages.

Turkey peritoneal exudate cells (PEC) and spermiophages (SMO) were assayed for characteristics of macrophages. The PEC elicited by i.p. injection of 3% Sephadex and SMO isolated from semen using Percoll were cultured in Dulbecco's Modified Eagle Medium supplemented with 20% bovine calf serum (DMEM-20) for 24 h at 41 C in 5% CO2 to provide adherent cells for assays. Most PEC and SMO showed esterase activity (99.3 +/- 0.6 and 98.8 +/- 0.9%, respectively), and exhibited nonspecific phagocytosis of carbon (89.5 +/- 3.6 and 95.3 +/- 0.6%, respectively), zymosan (26.5 +/- 7.6 and 24.3 +/- 2.5%, respectively), bacteria (11.3 +/- 0.8 and 9.3 +/- 0.3%, respectively), and opsonized and nonopsonized SRBC. Maximum uptake of SRBC was seen by 2 h for PEC but not until 4 h for SMO. At time of maximum uptake, SRBC were noted in 35 to 40% of PEC but only in 15 to 20% of SMO. Turkey IgG-FITC bound to both PEC and SMO, but goat anti-turkey IgG-FITC bound only to SMO. Increased nitrite was found in turkey semen after 24 h storage, with highest levels in samples in which SMO were added. Nitrite production was demonstrated using adhered PEC, but SMO could not be tested due to low cell numbers. This research clearly identifies SMO as having macrophage-like activities. Accordingly, these cells may possess the ability to process and present antigen via histocompatibility receptors. Such activity could lead to immune directed responses, including antibody production or activation of cytotoxic T-lymphocytes.

Animals↗

PubMed1997

Unexpected familial recurrence in Angelman syndrome.

We report on two instances of familial recurrence of Angelman syndrome which, from pedigree analysis, appear incompatible with currently known mechanisms of inheritance of this disorder. In these two families, deletion-positive Angelman syndrome has recurred in cousins. Several established mechanisms for deletion-positive familial recurrence have been ruled out. In each family, molecular cytogenetic studies show typical chromosome 15 deletions, and DNA methylation analysis verifies the maternal origin of the deleted chromosomes in all four individuals. Since the mothers of the affected individuals in each family are not known to be related, these recurrences appear to be secondary to coincidental, de novo events. This conclusion is consistent with direct and indirect estimates of the population frequency of Angelman syndrome.

Angelman Syndrome↗

PubMed1997

Clinical spectrum and molecular diagnosis of Angelman and Prader-Willi syndrome patients with an imprinting mutation.

Recent studies have identified a new class of Prader-Willi syndrome (PWS) and Angelman syndrome (AS) patients who have biparental inheritance, but neither the typical deletion nor uniparental disomy (UPD) or translocation. However, these patients have uniparental DNA methylation throughout 15q11-q13, and thus appear to have a mutation in the imprinting process for this region. Here we describe detailed clinical findings of five AS imprinting mutation patients (three families) and two PWS imprinting mutation patients (one new family). All these patients have essentially the classical clinical phenotype for the respective syndrome, except that the incidence of microcephaly is lower in imprinting mutation AS patients than in deletion AS patients. Furthermore, imprinting mutation AS and PWS patients do not typically have hypopigmentation, which is commonly found in patients with the usual large deletion. Molecular diagnosis of these cases is initially achieved by DNA methylation analyses of the DN34/ZNF127, PW71 (D15S63), and SNRPN loci. The latter two probes have clear advantages in the simple molecular diagnostic analysis of PWS and AS patients with an imprinting mutation, as has been found for typical deletion or UPD PWS and AS cases. With the recent finding of inherited microdeletions in PWS and AS imprinting mutation families, our studies define a new class of these two syndromes. The clinical and molecular identification of these PWS and AS patients has important genetic counseling consequences.

Adult↗

PubMed1997

NF1 mutation analysis using a combined heteroduplex/SSCP approach.

Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder characterized predominantly by neurofibromas, café-au-lait spots, and Lisch nodules. The disease is caused by disruptive mutations of the large NF1 gene, with half of cases caused by new mutation. Less than 100 constitutional mutations have thus far been published, ranging from very large deletions to point mutations. We have pursued NF1 mutation analysis by heteroduplex analysis (HDA) and single-strand conformational polymorphism analysis (SSCP) of individual exons. We streamlined these techniques to eliminate the use of radioactivity, to apply both methods to the same PCR product, and to multiplex samples in gels. Applied simultaneously to a set of 67 unrelated NF1 patients, HDA and SSCP have thus far identified 26 mutations and/or variants in 45 of the 59 exons tested. Disease-causing mutations were found in 19% (13/67) of cases studied. Both techniques detected a variety of mutations including splice mutations, insertions, deletions, and point changes, with some overlap in the ability of each method to detect variants.

Base Sequence↗

PubMed1997

A new point mutation in a hypoxanthine phosphoribosyltransferase-deficient patient.

A 12-year-old boy was referred because of abdominal pain, gross hematuria, and passage of stones. Further evaluation showed growth delay, low average range of intellectual functioning, and a speech articulation disorder. No signs of self-mutilation or self-injurious behavior were present. He had hyperuricemia, hyperuricosuria, uric acid crystalluria, uric acid calculi, macrocytosis, megaloblastic bone marrow changes, and mild anemia. Hypoxanthine phosphoribosyltransferase (HPRT) enzyme activity was reduced to approximately 26% of normal. Polymerase chain reaction-single strand conformational polymorphism analysis of the HPRT gene in DNA isolated from the patient's blood lymphocytes revealed a single nucleotide substitution at codon 200 in exon 8. The base change was a guanine to cytosine transversion, resulting in the conservative amino acid substitution of threonine in place of arginine. To our knowledge, this mutation has not previously been reported.

Child↗

PubMed1997

Purtscher-like retinopathy after uncomplicated administration of retrobulbar anesthesia.

PURPOSE: To report a case of Purtscher-like retinopathy after administration of retrobulbar anesthesia for an otherwise uncomplicated cataract extraction. METHOD: Case report. RESULTS: After cataract surgery with retrobulbar anesthesia, the patient followed a typical course of Purtscher-like retinopathy with an initial severe loss of vision followed by a gradual and nearly complete improvement in visual function. CONCLUSIONS: Purtscher-like retinopathy is uncommon after administration of retrobulbar anesthesia but had the same clinical course as other causes of this disorder.

Aged↗

PubMed1997

Chrysin and other leaf exudate flavonoids in the genus Pelargonium.

In a chemotaxonomic survey of 57 Pelargonium species, leaf exudate flavonoids were detected in 35% of the sample, mostly in trace amounts. However, chrysin and a related C-methylflavanone were identified as major leaf surface constituents of P. crispum, and a mixture of quercetin and kaempferol mono-, and di- and trimethyl ethers of P. quercifolium. In two other species, P. fulgidum and P. exstipulatum, methylated flavones were the only lipophilic flavonoids present. This is the first report of leaf surface flavonoids from the genus Pelargonium.

Chromatography, High Pressure Liquid↗

PubMed1997

Substance P released in the rostral brainstem of cats interacts with NK-1 receptors during muscle pressor response.

The release of immunoreactive substance P-like substances (irSP) was measured from sites in the rostral brainstem (at a level 1.3 mm anterior to the obex) of anesthetized cats in response to fatiguing isometric contractions using SP antibody-coated glass microprobes. The contractions caused a pressor and tachycardic response. irSP were released from sites in the medial subnucleus of the nucleus tractus solitarius (mNTS), the solitary tract and lateral tegmental field at this level of the brainstem. Injections of the specific NK-1 receptor antagonist, GR 82334, bilaterally into the mNTS significantly reduced the muscle pressor response, while bilateral injections of the SP NK-1 agonist, GR 73632, into the mNTS significantly increased the pressor and tachycardic responses during the contractions. Neither the antagonist nor the agonist, at the doses tested, affected the resting arterial pressure or heart rate. These data indicate that irSP are released from sites in the mNTS during the reflex pathways activated by isometric contractions and that they interact with NK-1 receptors in the area of the mNTS to affect the cardiovascular responses during the muscle pressor reflex.

Animals↗

PubMed1997

Effect of training on the aerobic power and anaerobic performance of prepubertal girls.

The purpose of this study was to investigate the effects of two, three times a week, 8-week training programmes on the aerobic power and anaerobic performance of 30 prepubescent girls, with a mean age of 9.6 y. Peak oxygen uptake assessed by an incremental discontinuous treadmill test, and peak power in 5 s and mean power over 30 s estimated from a Wingate anaerobic test were used as the criterion measures. Twelve girls trained using a continuous cycle ergometer programme, 11 girls followed a sprint running programme and the control group consisted of 7 girls. Both training groups significantly (p < 0.05) increased their peak oxygen uptake and peak power in 5 s. However, the increase reported here are lower than those generally observed in adolescents following training. The control group demonstrated no significant (p > 0.05) change in either variable. No significant (p > 0.05) changes in mean power over 30 s were observed in any group.

Anaerobic Threshold↗

PubMed1997

Children's and adolescents' anaerobic performance during cycle ergometry.

Cycle ergometry studies originated in the early 1900s but it was not until the early 1970s that the first studies of children and anaerobic performance were established. Since that time, research into the anaerobic performance of children and adolescents has proliferated, mainly due to attempts by investigators to overcome methodological problems. Besides the increase in studies using the most popular anaerobic test, the friction-braked Wingate, other tests such as the force-velocity and isokinetic cycle ergometers are becoming more common. No matter how the data are standardised, there is unequivocal agreement that children's and adolescents' anaerobic power scores are lower than those of adults. Qualitative muscular differences are often cited for this disparity rather than differences in the quantity of muscle, but conclusive research is lacking in this area. Despite the ethical considerations involved in studies with children, cycle ergometry has aided researchers to assess external short term power output, mean power and fatigue.

Adolescent↗

PubMed1997

Response to therapy in rheumatoid arthritis is influenced by immediately prior therapy.

OBJECTIVE: Clinicians do not often employ washout periods before prescribing a change in therapy for rheumatoid arthritis (RA). As a result, the observed effectiveness or lack of effectiveness of a new drug actually represents the effectiveness of that drug had the patient been taking placebo minus the residual effectiveness of the old drug. METHODS: We studied new starts of selected disease modifying antirheumatic drugs (DMARD) and prednisone in 2,898 patients with RA from 8 ARAMIS data bank centers, broken into subgroups on the basis of immediately prior therapy. Therefore, we examined the hypothesis that the chances of a treatment being observed effective depend upon the immediately preceding treatment. Using intent-to-treat analysis, we analyzed the effects upon Health Assessment Questionnaire (HAQ) disability and pain scores an average of 9 months after the new drug start. RESULTS: Methotrexate reduced disability significantly except after intramuscular gold or hydroxychloroquine and it reduced pain significantly after all prior therapies. Hydroxychloroquine reduced disability significantly after nonsteroidal antiinflammatory drugs (NSAID) only, but disability increased after intramuscular gold; pain was decreased only after NSAID only. Prednisone had no consistent effect upon disability but was consistently associated with decreased pain. Greatest effectiveness was always seen with a new drug start after NSAID only treatment versus after DMARD treatment. CONCLUSION: The effectiveness of a newly started RA treatment after 9 months may be substantially influenced by immediately prior treatment. This finding provides an additional reason for concern about direct extrapolation of clinical trial data into clinical practice.

Anti-Inflammatory Agents↗

PubMed1996

Juvenile rheumatoid arthritis in velo-cardio-facial syndrome: coincidence or unusual complication?

We report on two patients with velo-cardio-facial syndrome (VCFS) and juvenile rheumatoid arthritis (JRA). The first, a 9-year-old girl, presented with microcephaly, characteristic face, congenital heart disease, and velopharyngeal insufficiency. Fluorescence in situ hybridization (FISH) study showed deletion of D22S75 (N25), confirming the diagnosis of VCFS. At age 7, she developed joint pain, and polyarticular JRA was diagnosed. Awareness of this case led to the subsequent diagnosis of VCFS (also confirmed by FISH) in another, unrelated 12-year-old girl with characteristic face, hypernasal speech, and obesity. JRA was first diagnosed in this case at age 5 years, and she subsequently developed severe polyarticular disease. Neither patient had clinical or laboratory evidence of immunodeficiency. This observation represents the first report of the association of JRA with VCFS and raises the question of whether this is a coincidental association or a rare complication of this condition.

Arthritis, Juvenile↗

PubMed1996

Neuropeptide Y-like substances are released from the rostral brainstem of cats during the muscle pressor response.

1. In this study, the release of immunoreactive neuropeptide Y (NPY)-like substances (irNPYs) was measured from the rostral brainstem in response to fatiguing isometric contractions of the hindlimb muscle of cats anaesthetized with alpha-chloralose. 2. The irNPYs were measured using a solid phase autoradiographic immunoassay. NPY antibody-coated glass microelectrodes were inserted stereotaxically into the rostral brainstem during rest and contractions. Control procedures such as passive leg flexing, stimulation of the central end of the cut tibial nerve, brief repeated carotid occlusions and carotid sinus nerve stimulations were performed to determine whether patterns of release of irNPYs were specific to the pathways activated during the muscle pressor response. 3. During isometric contractions, the mean arterial blood pressure (MABP) and heart rate (HR) increased by 60-70 mmHg and 15-20 beats min-1, respectively. Only the brief carotid occlusions caused a similar increase in MABP and HR. 4. During isometric contractions, less irNPYs were released from sites in the lateral reticular nucleus, lateral tegmental field and vestibular nuclei at a level in the brainstem 4.0-4.4 mm rostral to the obex. In contrast, irNPYs were released from sites near the lateral tegmental field and nucleus ambiguus at a more caudal level tested (1.3 mm anterior to the obex) in response to contractions. Brief carotid occlusions caused a release of irNPYs from the lateral reticular nucleus on the contralateral side of the brainstem (at 3.5 mm anterior to the obex). None of the other procedures resulted in a release of irNPYs from these sites in the brainstem. 5. These data indicate there are differences in the patterns of release of irNPYs in response to activation of reflex pathways which increase arterial pressure. Given the sites in the rostral brainstem where irNPYs were released, irNPYs may be involved with the central regulation of arterial pressure during the muscle pressor response.

Animals↗

PubMed1996

Reduction in long-term disability in patients with rheumatoid arthritis by disease-modifying antirheumatic drug-based treatment strategies.

OBJECTIVE: Therapeutic strategies for rheumatoid arthritis (RA) have been evolving from the traditional "pyramid" approach toward one based upon early and sustained use of disease-modifying antirheumatic drugs (DMARDs), in the hope of improving long-term health outcomes. However, few data to have been presented to document the effects of this approach. We sought to directly assess associations between consistent DMARD use and long-term functional outcomes. METHODS: We studied 2,888 RA patients who were followed up prospectively for up to 20 years (average 9 years) at 8 databank centers. The independent variable was the proportion of patient encounters that resulted in treatment with > or = 1 DMARD (hydroxychloroquine, sulfasalazine, auranofin, intramuscular gold, D-penicillamine, methotrexate, and/or azathioprine). The dependent variable was each patient's last recorded Disability Index value from the Health Assessment Questionnaire (HAQ). RESULTS: Increased DMARD use was strongly associated with better long-term Disability Index values (P < 0.0001). The association was strengthened when restricted to more seriously affected (rheumatoid factor (RF)-positive) patients. The magnitude of the effect, unadjusted, was a difference of 0.53 HAQ Disability units (scale 0-3) between 100% DMARD use and 0%. Correlation coefficients ranged up to 0.26. Effects were similar for all disease duration periods (0-4, 5-9, 10-14, 15-19, and 20+ years). "Control" correlations, with variables computed to represent the proportion of time in which patients were taking either nonsteroidal anti-inflammatory drugs or prednisone, failed to show positive associations. A multiple linear regression model, which controlled for age, disease duration, sex, RF positivity, proportion of visits under a prednisone regimen, and initial disability level, included the proportion of time in which patients were taking DMARDs (P < 0.0001), with a model R2 of 0.54. These results were obtained despite an adverse selection bias in which more severely affected individuals were given DMARDS more frequently, and despite absence of data on drug use early in the disease course of many patients. Thus, these results, which suggest up to a 30 percent reduction in long term disability with consistent DMARD use, are most likely conservative. CONCLUSION: An association between consistent DMARD use and improvement in long-term functional outcomes in RA is supported by these data.

Antirheumatic Agents↗