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Biomedical subjects

R B Buckingham

Publications and source records attributed to R B Buckingham.

33 records · Page 2Linked to original sources

Collagen types synthesized in dermal fibroblast cultures from patients with early progressive systemic sclerosis.

Fibroblast cultures were established by explant culture from upper and lower dermis of 7 normal donors and 10 patients with early progressive systemic sclerosis (PSS). Antibodies against collagens containing the A and B chains, collagens which occur largely in vascular structures, were isolated and used for immunofluorescence studies. Cultures from lower PSS dermis accumulated significantly more of these collagens than fibroblast cultures from upper PSS dermis or cultures from upper or lower dermis of normal skin. These data indicate that the collagens containing the A and B chains in early PSS lesions are produced by cells of vascular origin and support the concept that alterations in vascular tissue play a prominent role in the pathogenesis of PSS.

Adult↗

Sjögren's syndrome in progressive systemic sclerosis.

Thirty-five consecutive patients with progressive systemic sclerosis were prospectively evaluated for evidence of Sjögren's syndrome. Six of the 35 (17%) were judged to have the disorder. This is a higher prevalence than in most reports, but much lower than that recently reportedly by Alarcón-Segovia and associates (7). An additional 17 of the 35 patients (48%) had significant fibrosis in the absence of sufficient mononuclear cell infiltrates to confirm the diagnosis of Sjögren's syndrome. This group had particularly aggressive scleroderma with serious visceral features, and five died after a short duration of illness. No significant abnormalities were found in biopsies from six patients with the mixed connective tissue disease syndrome, five with Raynaud's phenomenon alone, or in 29 autopsy control subjects who had no evidence of connective tissue disease. Fibrosis in the absence of mononuclear infiltration in minor salivary glands of patients with progressive systemic sclerosis indicates a poor prognosis.

Adult↗

Measurement of circumference of the knee with ordinary tape measure.

The circumference of the knees and thighs at three locations was measured in 10 patients on two consecutive occasions by three observers. Analysis of the results for interobserver, intraobserver and among-patient variation established that a change in circumference noted by different observers on two different days is significant if it exceeds 1-5 cm at the midpatella, 2-7 cm at 7 cm above, and 3-5 cm at 15 cm above the patella. If a single observer performs both measurements, the change need exceed only 1-0, 2-0, and 2-7 cm, respectively, to be significant.

Anthropometry↗

Rheumatoid behavior in normal human synovial fibroblasts induced by extracts of Gram-negative bacteria.

We have previously shown that exposure of normal human synovial cells to whole extracts of Gram-negative bacteria or purified endotoxins results in increased synthesis of hyaluronic acid, and increased glucose uptake and lactate output. Derivatives of Gram-negative bacteria, therefore, duplicate the major known actions of connective tissue activating peptide (CTAP). The studies presented here demonstrate that, in addition to the hypermetabolic changes, extract-treated synovial cells become hyposensitive to CTAP and acquire accelerated growth rates. Furthermore, the cellular alterations which occur following a short bacterial product-synovial fibroblast interaction period (72 hours) persist for varying lengths of time, in some cases for as long as the cells are followed in culture (up to 38 days). Additional data presented suggest that bacterial products induce CTAP formation or activation within synovial fibroblasts. Pre-incubation of bacterial endotoxin in fresh normal human serum does not alter its ability to activate synovial cells. Many of the cellular alterations induced by bacterial products and endotoxin (derivatives of infectious agents) resemble the abnormal metabolism of rheumatoid synovium in vivo and are characteristic of the behavior of rheumatoid connective tissue fibroblasts grown in vitro. Furthermore, the persistence of the bacterial extract-induced behavior resembles the semi-autonomy of the cultured rheumatoid synovial cell, at least for a limited period of observation.

Animals↗

Polyarthritis associated with type IV hyperlipoproteinemia.

Twelve patients had undiagnosed articular disease associated with type IV hyperlipoproteinemia. Objective joint findings involved both large and small joints. Disease was bilateral but asymmetrical and oligoarticular. Synovitis was midly inflammatory and persistent rather than episodic in natrue, and disability was minimal. Serial slinical, laboratory, and radiographic assessment excluded other currently recognized forms of rheumatic disease. Joint radiographs demonstrated large metaphyseal and epiphyseal cysts in five patients. Synovioanalysis and synovial biopsy results are reported in two patients. These cases appear to constitute a clinically homogeneous group. The concurrence of a distinctive articular syndrome and type IV hyperlipoproteinemia suggests a possible causal relationship.

Adult↗

The effect of bacterial products on synovial fibroblast function: hypermetabolic changes induced by endotoxin.

The effects of bacterial products on selected synovial fibroblast functions were studied. Extracts of commonly encountered microorganisms were prepared by sonic or mechanical disruption. "Purified" endotoxins were prepared from selected organisms, and in some cases were purchased commercially. Normal fibroblasts were derived from synovial connective tissue obtained from amputations or arthrotomy. The cells were grown as a monolayer on glass and were nourished by a semisynthetic nutrient medium. Extracts of Gram-negative bacteria, applied to fibroblast cultures, markedly increased hyaluronic acid production, glucose utilization, and lactate output. Treatment of the extracts with heat at 100 degrees C for (1/2) hr decreased their effectiveness by approximately 40%. Purified Gram-negative bacterial endotoxin stimulated synovial fibroblasts to an extent comparable to that caused by heat-treated whole extracts. The lipid moiety of the endotoxin molecule appeared to account for much of the stimulatory activity of the endotoxin. Extracts of commonly encountered Gram-positive cocci, yeast, and Mycoplasma had no stimulating capabilities. Corynebacterial extracts, however, had definite stimulating potential. Endotoxin-synovial cell interaction experiments demonstrated that endotoxin was bound to fibroblasts. Reassay of the endotoxin after extraction from the cells showed that it retained its stimulatory potential. The metabolic phenomena stimulated by bacterial products duplicate the major known actions of connective tissue-activating peptide (CTAP). The observations made in this study suggest that bacterial products may participate in a fundamental way in the activation process, and indicate a possible role for bacterial products in synovial inflammation in humans.

Cells, Cultured↗

Bleomycin-induced scleroderma.

Two men are reported who developed cutaneous fibrosis indistinguishable from that encountered in progressive systemic sclerosis (PSS, scleroderma) after treatment with the antitumor agent, bleomycin. In vitro study of the dermal fibroblasts of 1 patient showed that these cells synthesized increased quantities of collagen and therefore resembled cells derived from individuals with naturally occurring PSS. Bleomycin was shown to stimulate collagen production by cultured normal skin fibroblasts. Also, in 1 of the patients, bleomycin stimulated a lymphoproliferative response in vitro. These effects of bleomycin may be responsible for certain toxic reactions to this drug in the skin and lung.

Adult↗

Collagen accumulation by dermal fibroblast cultures of patients with linear localized scleroderma.

Two patients with linear localized scleroderma are reported. Punch biopsies from involved and contralateral site-matched uninvolved dermis of each patient were explained for the purpose of studying connective tissue accumulation in fibroblast monolayer culture. Monolayer cultures from involved tissue accumulated more collagen and glycosaminoglycan than cultures from uninvolved tissue for both patients. Augmented accumulation of collagen persisted for at least 11 subpassages. Involved monolayers acquired a strikingly different macroscopic appearance in confluent cultures.

Adolescent↗