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Biomedical subjects

C Pearson

Publications and source records attributed to C Pearson.

At least 73 records · Page 4Linked to original sources

The effect of oral retinoid therapy on the normal human immune system.

Twenty four patients were studied prior to and after 6 and 12 weeks therapy with isotretinoin (17 patients) for acne and related disorders, or with etretinate (7 patients) for psoriasis and related disorders. Patients treated with isotretinoin had a significant reduction in natural killer cell activity at an effector: target cell ratio of 100: 1 at 12 weeks and also a reduction in natural killer cell numbers at this time. Patients treated with etretinate had elevated natural killer cell activity and a significant elevation of natural killer cell numbers at 12 weeks. Other tests which were performed and showed no significant change at 6 or 12 weeks compared with starting levels included lymphocyte transformation in response to phytohaemagglutinin, pokeweed mitogen and concanavalin A, total numbers of circulating T lymphocytes, B lymphocytes and T helper and T suppressor subsets, numbers of epidermal Langerhans cells and serum levels of IgA, IgM and IgE. In view of the involvement of natural killer cells in the initial phase of organ rejection, these results suggest that isotretinoin is the safer of the two retinoids if administration to renal transplant recipients is considered, particularly in the immediate post-transplant period.

Acne Vulgaris↗

Absence of gradient of thyrotropin receptor antibody and T cell subset distribution between thyroid and peripheral venous blood in patients with Graves' disease prepared for surgery with carbimazole and potassium iodide.

The aim of the study was to examine tri-iodothyronine, thyroxine, thyroid antibody and thyrotropin receptor antibody levels in thyroid and peripheral venous blood at the time of surgery in patients with Graves' disease. T cell subset patterns in peripheral and thyroidal venous blood were compared to the distribution of T cell subset patterns within the thyroid gland itself. The results showed that at the time of surgery there were no significant differences in any of the parameters measured between thyroidal and peripheral venous samples. T cell subset patterns within the thyroid gland were subjectively similar to those in the venous samples.

Autoantibodies↗

Differential immunosuppressive action of carbimazole and propylthiouracil.

Carbimazole and Propylthiouracil (PTU) are widely used in the treatment of Graves' disease, although controversy still exists as to whether or not they have any direct effect on the immune system. While many previous studies have investigated the possible effects of one or other of these drugs on the immune system only a few have directly compared the effects of equivalent doses of each drug. This study aimed to examine the effects of both drugs, during the initial 8 weeks of treatment, on various biochemical and immunological parameters. The results obtained showed that while thyroid hormone levels fell at similar rates in both treatment groups, TRAb levels and T cell subset abnormalities returned towards normal more rapidly in patients receiving Carbimazole compared to PTU. These results indicate that the effects of Carbimazole on TRAb levels and T cell subset abnormalities are not due solely to its action in controlling the biochemical features of Graves' disease and provide indirect evidence of an action on the immune system in vivo.

Adult↗

Observations on the structure of two human 7SK pseudogenes and on homologous transcripts in vertebrate species.

A comparison of the sequence of two human 7SK RNA pseudogenes, covering approx. 190 and 240 base-pairs of the structural gene, is presented. Both repeated elements are flanked by direct repeats and begin at the 5' end of the gene. Each terminates approx. 90 base-pairs short of the 3' end, the latter representing a continuous sequence and the former carrying an internal deletion of about 40 base-pairs, this region being flanked in the progenitor gene by short repeated sequences. Southern blotting using a human 7SK pseudogene probe illuminated a series of multiple restriction fragments in mammalian genomes, with generally fewer fragments in the genomes of birds and reptiles and a single reactive fragment in DNA from terrapin (Pseudemys scripta elegans) and Xenopus laevis (South African clawed toad). In the latter case this fragment was only detectable on long exposure under the hybridization stringencies employed. 7SK transcripts were readily detectable in all mammalian, avian, reptilian and amphibian species analysed, although the gene appeared to be expressed at rather low levels in the ovaries of Xenopus laevis, possibly accounting for its failure to have become dispersed via 'retroposition' in this species.

Animals↗

In vitro comparison of antiplatelet effects of beta-lactam penicillins.

beta-Lactam antibiotics have been shown to cause platelet dysfunction and bleeding in some patients. However, relative antiplatelet activity of various beta-lactams has remained controversial. Results of clinical studies have been variable because of the presence of underlying disease in the study patients, in addition to inherent difficulties of in vivo experimentation such as individual variations of drug metabolism and drug kinetics. Thus, we designed in vitro experiments to study the direct effect of penicillin G, carbenicillin, ticarcillin, mezlocillin, piperacillin, nafcillin, and azlocillin on platelets. Platelets obtained from normal volunteers were exposed in vitro for 15 minutes to increasing concentrations of the test penicillins (10.0, 12.5, 15.0, and 20.0 mmol/L), and the platelet aggregation response determined after the additional of adenosine diphosphate (2.5 to 5.0 mumol/L), epinephrine (0.1 X 10(-3) mol/L), thrombin (0.01 to 0.02 U/ml), and collagen (11.62 micrograms/ml). All tested penicillins inhibited platelet aggregation in a saturable dose-dependent manner that was reversible by platelet washing. Biostatistical comparison of inhibition of platelet aggregation demonstrated nafcillin to cause significantly more inhibition, followed by azlocillin, mezlocillin, and piperacillin as a group. Penicillin G, carbenicillin, and ticarcillin were the least inhibitory. The mean percent inhibition (epinephrine) at 20 mmol/L concentration was nafcillin 86.4%, mezlocillin 83.2%, piperacillin 80.3%, azlocillin 76.4%, ticarcillin 73.2%, carbenicillin 66.4%, and penicillin G 58.4% (overall P less than 0.001). We conclude that all penicillins tested in vitro inhibit platelet aggregation in normal individuals, but to varying degrees. The inhibitory response, which is most likely a membrane-related phenomenon, is dose dependent and reversible.

Adenosine Diphosphate↗

Structural and transcriptional properties associated with a member of a new family of conserved short dispersed repeated elements in human DNA.

The sequence of a 500-bp segment of human DNA containing a member of the 'A3' family of dispersed repeated elements, a family hitherto uncharacterized in human or rodent DNAs, is presented. The repeated element maps to a region of 270 bp, within which the most notable features are 17-mer direct repeats separated by 190 bp. A probe containing the repeated element, together with flanking single-copy DNA illuminates a series of multiple bands in blot transfers of restriction digests of human, mouse and hamster DNAs. However, the flanking single-copy DNA hybridizes to human, but not to rodent DNA. The same probe illuminates homologous transcripts occurring in a single size class of 0.8 kb in total RNA from a variety of human and mouse cells, levels of which vary approx. 100-fold in the tissues analyzed. Poly(A)+ RNAs from EJ-transformed 3T3 cells and mouse fibrosarcomas have been analysed and found also to contain an homologous 0.8-kb transcript.

Animals↗

Polymyositis-dermatomyositis: diagnostic and prognostic significance of muscle alkaline phosphatase.

The distribution and intensity of alkaline phosphatase deposition in 54 patients with dermatomyositis-polymyositis (PM-DM) was analyzed by the enzyme histochemical method. Increased enzyme reactivity of endomysial capillaries was found in 28% of patients, equally distributed between adult onset PM (Group I) and PM-DM with overlap in other connective tissue diseases (Group V). Patients with high endomysial capillary reactivity (R1 larger than or equal to 60) responded poorly to steroids, had an increased incidence of rheumatoid factor, and had less fiber degeneration/necrosis in their biopsies. Twenty-two percent of patients demonstrated prominent perimysial phosphatase reactivity localized in newly formed collagen and fibroblasts. Thirty patients (55%) demonstrated significant numbers of alkaline-phosphatase-positive fibers positively correlated with increased fiber degeneration/necrosis, endomysial fibrosis, increased numbers of triglyceride-containing muscle fibers, and NADH tetrazolium reductase hyperreactivity. Minimal overlap between the three enzyme distribution patterns was found. Endomysial capillary activity probably represents endothelial alkaline phosphatase induction analogous to the pattern seen normally in lower mammals (rat, rabbit, guinea pig). Alkaline phosphatase fiber reactivity probably represents a particular phase in fiber regeneration/maturation especially after denervation and is positively correlated with an increased incidence of spontaneous fibrillation potentials in PM-DM.

Adult↗

Testing hearing with the brain-stem evoked response.

The brain-stem electroencephalograph (EEG)-evoked response (BSER) constitutes a reliable and objective method of testing hearing in infants, and in uncooperative, or retarded patients. The procedure is harmless and painless, and involves recording the EEG brain-stem responses to clicks presented by headphones. The patient may be sedated, or even anaesthetized, if necessary. Because of the equipment and time involved, the procedure is not recommended as a routine screening procedure, but constitutes a valuable adjunct to conventional audiological testing, especially in doubtful cases.

Adolescent↗

Indomethacin serum concentrations in man. Effects of dosage, food, and antacid.

In the use of anti-inflammatory compounds, sustained serum levels are thought to be related to drug efficacy. This study shows that frequent clinical administration of indomethacin can result in sustained serum levels of the drug and that food and antacid may have important modifying effects on serum indomethacin concentrations. After oral ingestion by fasting subjects, indomethacin rapidly appeared in the serum, usually reaching peak concentrations in 30 to 90 minutes. Food delayed and decreased the mean peak level; antacid delayed the peak and slightly enhanced subsequent concentrations. With multiple dose schedules plateau levels were reached after 24 hours. When a total daily dose of 150 mg was given as 25 mg every 4 hours peak concentrations were the same but fluctuations were smaller and average concentrations were higher than with a dosage of 50 mg every 8 hours.

Administration, Oral↗