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Biomedical subjects

R G Davidson

Publications and source records attributed to R G Davidson.

At least 19 recordsLinked to original sources
PubMed1991

Characterization of arylsulfatase C isozymes from human liver and placenta.

Arylsulfatase C and steroid sulfatase were thought to be identical enzymes. However, recent evidence showed that human arylsulfatase C consists of two isozymes, s and f. In this study, the biochemical properties of the s form partially purified from human placenta were compared with those of the f form from human liver. Only the placental s form has steroid sulfatase activity and hydrolyses estrone sulfate, dehydroepiandrosterone sulfate and cholesterol sulfate. The liver f form has barely detectable activity towards these sterol sulfates. With the artificial substrate, 4-methylumbelliferyl sulfate, both forms demonstrated a similar KM but the liver enzyme has a pH optimum of 6.9 while the placental form displayed two optima at 7.3 and 5.5. The molecular weight of the native enzyme determined with gel filtration was 183,000 for the s form and 200,000 for the f form and their pI's were also similar at 6.5. However, the T50, temperature at which half of the enzyme activity was lost, was 49.5 degrees C for the f form and 56.8 degrees C for the s form. Polyclonal antibodies raised against the placental form reacted specifically against the s and not the f form. They immuno-precipitated concomitantly greater than 80% of the total placental arylsulfatase C and steroid sulfatase activities while less than 20% of the liver enzyme was immuno-precipitable. In conclusion, the two isozymes s and f of arylsulfatase C in humans purified from placenta and liver, respectively, have similar KM, pI' and native molecular weight. However, they are distinct proteins with different substrate specificity, pH optima, heat-lability and antigenic properties. Only the s form is confirmed to be steroid sulfatase.

Arylsulfatases↗
PubMed1991

Evaluation of cartilage lesions by magnetic resonance imaging at 0.15 T: comparison with anatomy and concordance with arthroscopy.

Recent evidence suggests that pharmacological treatment may alter the rate of progression of cartilage damage in osteoarthritis (OA). However, a lack of accurate and precise noninvasive assessments of cartilage structure makes it difficult to answer this question directly with prospective clinical trials, prevents early diagnosis of OA and restricts assessment of treatment to evaluation of symptoms or joint function. It is important, therefore, to develop precise, noninvasive methods both for diagnosis of early OA before damage is extensive and irreversible and for evaluation of therapeutic effectiveness. Magnetic resonance imaging (MRI) allows for noninvasive, multiplanar body imaging which depends on proton density, flow, and the T1 and T2 relaxation times. Because these variables differ markedly among joint tissues, cartilage erosions are visible with MRI and it should be possible to quantify them. Our objective was to compare MRI with arthroscopy for assessing the depth of lesions in the articular cartilage of human knees to help develop and validate MRI for use in clinical trials designed to assess the effect of therapy on cartilage structure. In the first part of our study, the effect of the MRI pulse sequence variables on the images was evaluated by varying them systematically and comparing the anatomy seen with MRI with that seen at arthroscopy or arthrotomy and with the histology. In the second part, 31 patients were assessed with MRI before arthroscopy. The MRI were graded on a 4-point ordinal scale by 2 observers who were unaware of the clinical diagnosis and compared with findings at arthroscopy which were graded using the same scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Arthroscopy↗
PubMed1990

The human arylsulfatase-C isoenzymes: two distinct genes that escape from X inactivation.

Arylsulfatase C is a microsomal membrane-bound enzyme previously thought to be the same as steroid sulfatase, the only X-linked enzyme known to escape from X inactivation in man. We had shown that arylsulfatase C actually consists of two biochemically distinct isozymes, s and f. Only the s form has steroid sulfatase activity. The f and s forms were thought to be related through posttranslational or posttranscriptional modification of the same gene product. In part consistent with this hypothesis, we now report that in a panel of 28 rodent-human somatic cell hybrids, expression of both s and f was concordant only with the human X chromosome, thus showing that the f form is also X linked. In three separate somatic hybrids containing human X chromosomes in an inactive state, the f form was still expressed. Thus, similar to the s form, the f form also escapes from X inactivation. However, contrary to expectations, the s and f forms were not related by posttranslational modification of the same gene product. A full-length cDNA for the s form failed to hybridize to transcripts produced from an f-expressing cell line, showing that there is little sequence identity between the two. They are also not related by differential splicing of a common primary transcript, since fibroblasts from some patients with steroid sulfatase deficiency due to gene deletion of the s form continue to express the f form. Therefore, although the f and s isozymes of arylsulfatase C are X linked and escape from X inactivation, they are products from separate genes, thus providing a unique isoenzyme system to study possible gene duplication and regulation in the part of the human X chromosome that escapes inactivation.

Animals↗
PubMed1989

Cysts of the lateral meniscus: arthroscopy versus arthroscopy plus open cystectomy.

A retrospective analysis was performed on 32 knees in 31 patients with the diagnosis of cyst of the lateral meniscus. Average follow-up was 41 months, with a range of 16-72 months. Surgical and histological examination demonstrated pathology varying from large meniscal tears with minimal cyst formation to large cysts with no demonstrable meniscal tear. Two theories of etiology emerged: (a) The tear begins in the meniscus and spreads through the periphery. (b) The lesion begins as a compression injury to the vascular periphery and spreads centrally, producing a meniscus tear, or peripherally, producing a cyst, or both. In our series, 20 patients managed by arthroscopic partial meniscectomy and open cystectomy had 80% excellent-good results versus 50% excellent-good results in 12 patients treated with arthroscopy and partial meniscectomy without extraarticular cystectomy. We recommend the following treatment: arthroscopy with a diligent search for a lateral meniscal tear, especially peripherally. If none is found, proceed to extraarticular cystectomy. If a tear is found, remove all unstable meniscal fragments, leaving a rim, if possible, especially adjacent to the popliteus recess, and then proceed to open cystectomy.

Arthroscopy↗
PubMed1988

Atlantoaxial instability in individuals with Down syndrome: a fresh look at the evidence.

In 1984, the Committee on Sports Medicine of the American Academy of Pediatrics published in this journal a statement on the remarkably high incidence of atlantoaxial instability among individuals with Down syndrome. On the assumption that this instability, demonstrable through a specified series of lateral x-ray films of the neck, constituted a predisposition to cervical spine dislocation with subsequent spinal cord compression, the Academy supported and made more specific a series of recommendations that had originated from the Kennedy Foundation a year previously. In essence, for those persons who are found to have the radiographic sign of instability, participation in sports should be restricted. Because the implementation of these recommendations could deprive tens of thousands of individuals with Down syndrome of activities that are emotionally and physically beneficial and because of the rarity of reported cervical dislocations associated with injury, a case review was done. Included were those cases cited as support for the recommendations along with additional reports that had been omitted and a few cases reported subsequently. Little support for the hypothesis that atlantoaxial "instability" is a predisposing factor to "dislocation" was found, although much was found to indicate an urgent need for carefully designed longitudinal studies. Because nearly all of the cases of actual dislocation were preceded by at least several weeks of readily detectable physical signs, a physical examination with careful attention to neurologic signs prior to participation in sports is more predictive of potential or impending dislocation than the radiologic criteria currently recommended.

Atlanto-Axial Joint↗
PubMed1987

Neonatal manifestations of Schwartz-Jampel syndrome.

Schwartz-Jampel syndrome generally presents in childhood with short stature, limited joint mobility, masklike facies with blepharophimosis, myotonia, and often muscle hypertrophy. Few cases with neonatal manifestations have been described. A newborn with severe manifestations is reported and the literature is reviewed.

Electromyography↗
PubMed1987

Prenatal diagnosis of retinal detachment in Walker-Warburg syndrome.

Lissencephaly, hydrocephalus, and eye abnormalities characterize patients with the Walker-Warburg syndrome, an uncommon autosomal recessive condition. Encephaloceles occur in about 50% of patients. We describe the prenatal diagnosis of this condition based on the ultrasonographic findings of retinal detachment, hydrocephalus, and an encephalocele in a fetus not known to be at risk.

Abnormalities, Multiple↗
PubMed1986

Association of steroid sulfatase with one of the arylsulfatase C isozymes in human fibroblasts.

When arylsulfatase C, a microsomal membrane-bound enzyme, is assayed with its natural substrates, the 3-beta-hydroxysteroid sulfates, it is also known as steroid sulfatase. Whether arylsulfatase C and steroid sulfatase are identical enzymes or not, however, has long been disputed. We now report that two electrophoretic variants of arylsulfatase C occur in normal human fibroblasts: one has a single anodic band of activity, "s," and the other has an additional faster migrating band, "f". The two types, s and "f + s", occur in cells from either sex. When fibroblast strains with the f + s forms of arylsulfatase C were cloned, two types of primary clones were always obtained: s and f + s. A single f band was never seen. When these primary clones were subcloned, however, the arylsulfatase C phenotype remained unchanged: primary s clones gave rise to s subclones and f + s clones to f + s subclones only. Therefore, these forms were clonal in origin and demonstrated a novel inheritance pattern in human cultured cells. The appearance of increasing amounts of the f band was correlated with up to 4-fold increase of arylsulfatase C activity, whereas the steroid sulfatase activity remained constant, thus demonstrating that arylsulfatase C was not identical with steroid sulfatase activity. Polyclonal antibodies raised against the s form immunoprecipitated activities of the s form of arylsulfatase C and steroid sulfatase but not the f form of arylsulfatase C. Therefore, we conclude that only the s form of arylsulfatase C is immunologically related to steroid sulfatase so that arylsulfatase C per se is not necessarily identical with steroid sulfatase. In addition, a novel form of genetic heterogeneity of isozymes in human fibroblasts is demonstrated.

Antigen-Antibody Complex↗
PubMed1986

Abdominal distension in Kaufman-McKusick syndrome.

A female infant with Kaufman-McKusick syndrome redeveloped respiratory distress and abdominal distention at 5 weeks of age. Ultrasonography demonstrated recurrence of peritoneal cysts and hydrometrocolpos. It is postulated that refluxing vaginal secretions may contribute to the abdominal distention seen in many infants with Kaufman-McKusick syndrome.

Abdomen↗
PubMed1985

Action of surface-active agents on arylsulfatase-C of human cultured fibroblasts.

Arylsulfatase-C is a microsomal membrane-bound enzyme with unusual biochemical and genetic properties. Whether it is a single enzyme hydrolyzing different sterol sulfates or a complex of enzymes, with each enzyme hydrolyzing a specific substrate, has not been resolved. Its locus has been mapped to the human X chromosome but appears to escape inactivation. As a first step to clarify its biochemical properties, a systematic search was undertaken for a suitable detergent that can release this enzyme from human cultured fibroblast membranes in a form that is biologically active and electrophoretically mobile. Four non ionic (Triton X-100, Nonidet P-40, Digitonin, and saponin) and four amphoteric (lysolecithin, Zwittergent, Miranol, and Chaps) detergents were studied. At 1% concentration, they released more than 80% of the activity into a low-speed supernatant fraction, except for Saponin which had no effect. With Triton X-100 and Miranol representing the two groups of detergents, significant release occurred only when the detergent concentrations exceeded their respective critical micelle concentrations, thus indicating that arylsulfatase-C is an integral membrane protein. The apparent molecular weight of the detergent-enzyme complex, ascertained by gel filtration, was 85,000 in the presence of Triton X-100 and 335,000 in the presence of Miranol. However, only the preparation solubilized by Miranol (and Chaps, to a lesser degree) permitted migration of the enzyme in nitrocellulose acetate during electrophoresis at pH 7.0, while the enzyme extracted with all other detergents remained at the origin. Therefore, the amphoteric detergent, Miranol, appears to fulfill the requirements for further characterization of the membrane-bound arylsulfatase-C in human cultured fibroblasts.

Arylsulfatases↗
PubMed1985

A survey of injuries to the anterior cruciate ligament of the knee in female basketball players.

This study surveyed 76 female basketball-related injuries that occurred during a 30-month period at the B.C. Sports Medicine Clinic. The knee was the most common site of injury (72%), and anterior cruciate ligament (ACL) rupture accounted for 25% of all basketball injuries seen. A total of 19 ACL ruptures in females were seen as compared to only 4 ACL ruptures in male basketball players during the same time period. During this time period a total of 151 males and 76 female basketball players were seen. Each patient was assessed as to age, height, weight, and alignment and questioned as to mechanism of injury, playing position, experience, and training plus previous injuries. Possible etiological factors postulated included player position, joint laxity, weak quadriceps mechanism, and a possible hormonal basis.

Adolescent↗
PubMed1984

Diagnosis of pseudo-arylsulfatase A deficiency with electrophoretic techniques.

Deficient arylsulfatase A activity in man has long been associated with the neurodegenerative disease, metachromatic leukodystrophy. However, similar deficiency has been noted in clinically normal individuals, and is referred to as the pseudoarylsulfatase A deficiency condition. Although direct quantitative analysis of arylsulfatase A activity failed to differentiate between these two conditions, analysis of residual arylsulfatase A activity with either Cellogel electrophoresis or isoelectric focusing in polyacrylamide gels now has been shown to distinguish between them unequivocally. With both techniques, cultured fibroblasts from patients with pseudo-arylsulfatase A deficiency showed faint but clear bands of arylsulfatase A activity. Under identical conditions, fibroblasts from patients with metachromatic leukodystrophy showed no trace of activity. These methods can be adapted easily for general laboratory analysis in cases when results from quantitative arylsulfatase A assays are noninformative.

Cerebroside-Sulfatase↗
PubMed1984

Post-natal development of interscapular (brown) adipose tissue in the guinea pig: effect of environmental temperature.

The post-natal development of interscapular brown adipose tissue (BAT) was studied in the guinea pig by monitoring changes in DNA, triglycerides and mitochondrial protein as well as the activity of cytochrome oxidase and atractyloside insensitive GDP-binding. The results demonstrate that neonatal brown fat develops into a tissue with the gross characteristics of white adipose tissue. In this respect the post-natal development of guinea pig BAT is analogous to that of the tissue in man. Furthermore the apparent transformation is not irreversible since cold exposure (+4 degrees C) of adult guinea pigs for six weeks resulted in restoration of cytochrome oxidase, GDP-binding, etc, to levels characteristic of neonatal BAT. However, the interscapular fat pad temperature response to noradrenaline and the presence of 32 000 mol. wt mitochondrial inner membrane protein indicate that the tissue retains thermogenic activity even in warm acclimated adult guinea pigs.

Adipose Tissue, Brown↗
PubMed1983

Biochemical variability of arylsulphatases -A, -B and -C in cultured fibroblasts from patients with multiple sulphatase deficiency.

Multiple sulphatase deficiency (MSD) in man is inherited as an autosomal recessive trait and associated with deficient activities of various sulphohydrolases. Cultured fibroblasts from seven different patients were assayed for arylsulphatases-A, -B and -C activities. On the basis of the results, they may be classified into three groups: I, deficient in all three arylsulphatases; II, deficient only in arylsulphatases-A and -C with half or near-normal arylsulphatase-B; electrophoretically, arylsulphatase-A activity bands are undetectable as in metachromatic leukodystrophy; III, same as in II except electrophoretically, the residual arylsulphatase-A is detectable as faint activity bands similar to those in pseudo arylsulphatase-A deficiency. In addition to the variability among different strains, within the same strain of MSD or normal cells, each enzyme activity increased several fold with increasing time in culture. These sources of biochemical variability among and within different cell strains have not been recognized before in the study of this apparently monogenic trait with multiple enzyme deficiencies. They may account for some of the discrepancies reported in the literature on arylsulphatase activities among cultured cells from different multiple sulphatase deficient patients.

Arylsulfatases↗