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Biomedical subjects

P J Clements

Publications and source records attributed to P J Clements.

At least 19 recordsLinked to original sources
PubMed1979

A syndrome resembling progressive systemic sclerosis after bone marrow transplantation. A model for scleroderma?

Six long term survivors of bone marrow transplants developed a syndrome similar to progressive systemic sclerosis (PSS). Cutaneous involvement (6/6), pulmonary disease (6/6), musculoskeletal involvement (4/6), keratoconjunctivitis/positive Schirmer's test (4/6), Raynaud's phenomenon (2/6), and renal and cardiac disease (1/6) were similar to findings in PSS patients. T and B lymphocyte counts and functions were also similar. This PSS-like syndrome, including visceral involvement, after bone marrow transplantation lends support to an immunologic hypothesis of the pathogenesis of progressive systemic sclerosis.

Antigen-Antibody Complex↗
PubMed1979

Esophageal motility in progressive systemic sclerosis (PSS). Comparison of cine-radiographic and manometric evaluation.

The evaluation of structural and functional abnormalities of the esophagus by manometry (using perfused tubes) and cine-radiography were compared in 25 subjects with progressive systemic sclerosis (PSS). Motility by both procedures was definitely abnormal in 19 subjects and normal in 3. The remaining 3 subjects had abnormal motility on manometry, coupled with cine-esophagrams interpreted as normal. Many structural abnormalities not demonstrated by manometry were identified by cine-radiography. Therefore, the initial diagnostic examination of motility in PSS should be the cine-esophagram.

Cineradiography↗
PubMed1979

Small airways in progressive systemic sclerosis (PSS).

Obstructive disease involving peripheral airways has been noted in diffuse interstitial pulmonary disease, including sarcoidosis and cryptogenic fibrosing alveolitis. The possibility of obstruction of small airways in progressive systemic sclerosis (PSS) has been suggested by widespread bronchiolectasis and peribronchial fibrosis noted at necropsy. We performed pulmonary function studies in 39 subjects (22 nonsmokers and 17 smokers) with PSS, most of whom had functional evidence of interstitial pulmonary involvement (increased static recoil pressure and reduced diffusing capacity). The 1 second forced expiratory volume to forced vital capacity ratio (FEV1:FVC) was normal in all subjects. Although the severity of the restrictive process was greater in nonsmokers compared with that in smokers, the maximal mid-expiratory flow rate, closing volume, closing capacity, volume of isoflow, change in maximal expiratory flow at 50 per cent of vital capacity during 80 per cent helium--20 per cent oxygen breathing compared with air breathing (delta Vmax50), ratio of dynamic to static lung compliance at different breathing frequencies and upstream airway conductance at static recoil pressures of 5 and 10 cm H2O were nearly always normal in the nonsmokers but were frequently abnormal in the smokers with PSS. These findings suggest that diffuse interstitial pulmonary disease due to PSS generally does not lead to functional evidence of obstruction in peripheral airways and that when the latter is found it can likely be attributed to the effects of concomitant cigarette smoking.

Adult↗
PubMed1979

Measurement of clinical change in progressive systemic sclerosis: a 1 year double-blind placebo-controlled trial of N-acetylcysteine.

N-acetylcysteine was employed as a therapeutic agent in a 1-year, parallel, double-blind, placebo-controlled, prospective study of 22 patients with progressive systemic sclerosis (PSS). Patients were closely followed-up and were extensively evaluated at baseline, 6 and 12 months. Most parameters remained unchanged during 1 year of study in both the NAC and placebo groups, which showed the need for prolonged studies of drugs in PSS if definitive results are to be obtained. Over the year of the study the diffusing capacity decreased in both groups, while several other parameters measured both increased and decreased. Several simple measures of function and skin distensibility were tested and two (oral aperature and handspread) were reproducible and sensitive enough to measure moderate changes of disease activity. They may be useful in future trials of drug effect in PSS.

Acetylcysteine↗
PubMed1978

Association of HLA antigen a9 with progressive systemic sclerosis (scleroderma).

Upon evaluation of 40 subjects with progressive systemic sclerosis (PSS), a significant association of HLA antigens A9 and Aw24 (a subgroup of A9) was found with diffuse scleroderma. HLA-Aw23 (a second subgroup of A9) was also increased in the patients, however, this was not statistically significant. Diffuse scleroderma appears to be one of the few diseases that shows an association with the HLA-A locus.

Epitopes↗
PubMed1978

Glucocorticoids administered in vivo inhibit human suppressor T lymphocyte function and diminish B lymphocyte responsiveness in in vitro immunoglobulin synthesis.

The effects of corticosteroid given in vivo on human lymphocyte subpopulation function were investigated using an in vitro system of pokeweek mitogen-stimulated immunoglobulin production. Peripheral blood lymphocytes were obtained from normal volunteers before and 4 h after the intravenous administration of methylprednisolone. Unfractioned peripheral blood lymphocytes showed a consistent decrease (mean congruent with 50%) in immunoglobulin and total protein synthesis after steroid administration. Utilizing separated thymus-derived (T) and bone marrow-derived (B) lymphocyte fractions, the pathophysiology of this alteration in immunoglobulin production was elucidated. B lymphocytes obtained after steroid treatment showed a markedly diminished immunoglobulin response (20% of normal) to normal T lymphocytes and to normal T cells that had been irradiated to remove suppressor T lymphocyte function. All major classes of immunoglobulin (IgG, IgM, and IgA) were affected. T lymphocytes procured after steroid administration were capable of providing normal amounts of T cell help for B cells in immunoglobulin production. However, suppressor T lymphocyte activity, observed with normal T lymphocytes at high T to B cell ratios, was absent from the post-steroid T lymphocytes. This loss of suppressor T lymphocyte function was not due to the presence of excess help as irradiated pre- and poststeroid T cells provided equal amounts of helper activity. On recombining the poststeroid treatment B cells, which are hyporesponsive in immunoglobulin synthesis, with the posttreatment T lymphocytes, which lack suppressor activity, diminished amounts of immunoglobulin were produced which correlate well with the effects observed with unseparated cells. Thus, corticosteroids have differential effects on the lymphocyte populations involved in immunoglobulin biosynthesis. B cell responsiveness is diminished, suppressor T lymphocyte activity is removed, and helper T lymphocyte function is unaffected.

Adult↗
PubMed1978

Cellular collaboration in the production of human leucocyte migration inhibition factor.

The participation of cell subpopulations in the expression of leucocyte migration inhibition factor (LMIF) in response to Concanavalin A and Protein A was evaluated for cells isolated from the peripheral blood of five healthy subjects. LMIF activity could not be attributed to the function of T cells, B enriched cells, or monocytes acting alone, or to a combination of B enriched cells and monocytes. The LMIF response was the result of a collaborative event that occurred between T cells and B enriched cells, or between T cells and monocytes.

B-Lymphocytes↗
PubMed1978

Effect of corticosteroids on the human immune response: comparison of one and three daily 1 gm intravenous pulses of methylprednisolone.

In spite of the increasing use of single and multiple pharmacologic intravenous pulses of MPS for immunosuppression in various diseases, their immunosuppressive effects have not been documented. We treated two groups of six patients with classic RA unresponsive to conventional therapy with either one or three daily 1 gm intravenous doses of MPS and measured the immune response and clinical activity over 16 weeks. Lymphocytopenia with selective T lymphocyte suppression was noted 2 hr following each infusion, which was maximal at 6 hr with complete recovery 24 hr after each dose beyond which no lymphocytopenia or T lymphocyte depletion was seen. Preservation of skin test positivity to recall antigens such as PPD and histoplasmin, rise in antibody titers to the secondary antigens tetanus and typhoid, and primary antibody response to KLH were found in both groups after treatment. Serum gamma globulin concentrations were unchanged. Five of six patients receiving 3 doses and three of six receiving 1 dose had satisfactory improvement in clinical parameters, with maximal benefit seen within the first 4 days. Six patients still felt better at 4 weeks, and one patient in each group entered a clinical remission greater than 16 weeks. We conclude that higher and repeated doses of MPS caused neither greater lymphocytopenia nor more prolonged suppression of recirculating lymphocytes than the conventional oral doses. The clinical benefits stem from reduction of inflammation, and it is doubtful that pulse therapy by itself induced significant generalized immunosuppression.

Aged↗
PubMed1977

Lymphocyte abnormalities in ankylosing spondylitis.

Peripheral blood T (SRBC rosette) and B (AgG- and C-receptor) lymphocyte subpopulations and responsiveness to phytohaemagglutinin (PHA) were assayed in 40 patients with ankylosing spondylitis and in 55 normal subjects. There was no significant difference in the lymphocyte concentrations or responsiveness to PHA between the two groups. However, the percentages of T lymphocytes were significantly lower in the patients irrespective of their HLA typing. This was probably due to an increase in the 'null' population since the percentages of both the AgG- and C-receptor cells were normal.

Humans↗
PubMed1977

Oral radiographic changes in patients with progressive systemic sclerosis (scleroderma).

Intraoral and panoramic radiographs were made of 35 patients with progressive systemic sclerosis. Of those patients, 13 (37%) were found to have abnormally thickened periodontal ligament spaces. Six of the 35 demonstrated mild to significant resorption of the posterior mandibular angle. Three patients, including two showing angle resorption also had some degree of coronoid process destruction. All patients with this disease should receive initial and follow-up panoramic radiographic examinations to determine any osseous changes.

Adult↗