PubMed Health⌕ Search

Biomedical subjects

R Paine

Publications and source records attributed to R Paine.

17 recordsLinked to original sources
PubMed1992

Hard metal pneumoconiosis and the association of tumor necrosis factor-alpha.

Hard metal pneumoconiosis is a recently recognized occupational lung disease associated with the exposure to cobalt fumes in the workplace. Chronic exposure in susceptible individuals results in interstitial lung disease histopathologically manifested as interstitial fibrosis with an associated mononuclear cell infiltrate and the presence of "cannibalistic" multinucleated giant cells in the alveolar airspaces. The majority of patients present with symptoms of chronic cough and dyspnea. Interestingly, in addition, patients uniformly report significant weight loss out of proportion to their degree of respiratory impairment. In this case report we demonstrate the association of tumor necrosis factor-alpha (TNF) and hard metal (cobalt) pneumoconiosis and suggest that TNF may have a potential role in the etiology of the constitutional symptoms and the pathogenesis of interstitial lung disease.

Adult↗
PubMed1992

A factor secreted by a human pulmonary alveolar epithelial-like cell line blocks T-cell proliferation between G1 and S phase.

Because the pulmonary alveolar space is both the site of gas exchange for respiration and a portal of entry for foreign antigen, immunologic interactions within that space must be meticulously controlled. Alveolar epithelial cells are ideally situated to play a role in immune regulation within the alveolar space. We have used A549 cells, a cell line that is derived from a human alveolar cell carcinoma and that has been used as a model for alveolar type II epithelial cells, to examine the potential role of alveolar epithelial cells in local pulmonary immune regulation. Medium conditioned by confluent monolayers of A549 cells suppressed proliferation by human peripheral blood mononuclear cells (PBMC) stimulated with lectin, anti-CD3 antibodies, calcium ionophore and phorbol ester, or in a mixed leukocyte reaction. PBMC that had been incubated in and then removed from A549-conditioned medium went on to proliferate normally. Because the suppressive effect was abrogated by heating or acidification and was not blocked by neutralizing antibody to transforming growth factor-beta 1, this effect could not be attributed to transforming growth factor-beta. The factor mediating this effect has an approximate molecular weight of 70,000 D by gel filtration chromatography. Nonalveolar, pulmonary carcinoma cell lines did not exert this immunosuppressive influence nor did the alveolar epithelial cells inhibit proliferation by the transformed, Jurkat, T-cell line. Cell cycle analysis demonstrated that PBMC exposed to A549 cell-conditioned medium failed to enter S phase after mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological Factors↗
PubMed1991

Signal transduction via CD4, CD8, and CD28 in mature and immature thymocytes. Implications for thymic selection.

The positive and negative selection of immature thymocytes that shapes the mature T cell repertoire appears to occur at an intermediate stage of development when the cells express low levels of TCR/CD3. These cells are also CD4+CD8+ and CD28+ (dull), and signals delivered by these three accessory molecules have been implicated in the selection process. We have examined the regulatory function of these accessory molecules on responses of immature thymocytes stimulated through the TCR/CD3 complex. Cross-linking CD4 or CD8 with CD3 strongly enhanced signal transduction via CD3 as assessed by protein tyrosine phosphorylation and calcium mobilization. Subsequent cell proliferation could be induced by soluble anti-CD28 mAb, which was comitogenic for cells stimulated with CD3 x CD4 or CD3 x CD8 cross-linking, but was without effect on cells stimulated with CD3 x CD3 cross-linking. A potential role for CD28 signal transduction in thymic maturation is suggested by the demonstration that the BB-1 molecule, a natural ligand for CD28, is expressed on thymic stromal cells. Taken together, our data suggest a model of thymic development in which CD4 or CD8 may enhance TCR/CD3 signaling upon coligation by an MHC molecule. If the CD28 surface receptor is simultaneously stimulated by a BB-1 expressing stromal cell, this set of interactions could lead to proliferation and positive selection. In the absence of CD28 stimulation the enhanced TCR/CD3 signals might lead to apoptosis and negative selection.

Antibodies, Monoclonal↗
PubMed1991

Alveolar epithelial cells block lymphocyte proliferation in vitro without inhibiting activation.

In the face of constant exposure to inhaled antigens, precise local regulation of immune responses in the pulmonary alveolar space is essential to achieve a delicate balance between host defense and excessive immune responses that are incompatible with the primary physiologic function of the lung. We postulated that the cells of the alveolar epithelium may have an immunoregulatory role in the lung. Therefore, we have examined the effects of primary cultures of rat type II alveolar epithelial cells on lymphocyte proliferation and on the expression of a number of markers of T-cell activation. Monolayers of alveolar epithelial cells suppressed proliferation and DNA synthesis by concanavalin A-stimulated rat splenocytes. Suppression of [3H]thymidine incorporation was independent of the dose of mitogen and was also apparent when lymphocytes were stimulated with phorbol esters and calcium ionophore, suggesting that the effect was independent of cell surface binding of the lectin. Suppression was reversed 48 h after lectin-stimulated splenocytes were removed from co-culture with alveolar epithelial cells. Despite inhibition of lymphocyte proliferation, other markers of T-cell activation were induced normally in lymphocytes cultured with alveolar epithelial cells. Culture with alveolar epithelial cells did not inhibit the the production of interleukin-2 by stimulated lymphocytes. Furthermore, by fluorescence-activated cell sorter analysis, equal proportions of stimulated lymphocytes in culture alone or with alveolar epithelial cell monolayers were induced to express receptors for interleukin-2 and for transferrin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro.

Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung.

Animals↗
PubMed1990

Serum accelerates the loss of type II cell differentiation in vitro.

The differentiated phenotype of the alveolar type II cell is rapidly altered in vitro. To evaluate factors that might influence this process, we isolated and plated rat type II cells in serum-supplemented media to promote adherence and then maintained the cells in a simple nutrient medium in the absence (S- cells) or presence (S+ cells) of serum for 5 to 7 d. The type II S- cells remained metabolically active. Despite protein synthesis that was 50% that of S+ cells, S- cells continued to synthesize a broad spectrum of proteins and to express several features of type II cell differentiation. They synthesized an apical integral membrane glycoprotein, Maclura pomifera agglutinin (MPA)-gp200, and a cytokeratin, No. 19, while S+ cells did not. When supplemented with linoleic acid, S- cells contained lamellar and multivesicular bodies, incorporated cell surface MPA into these structures, and secreted their phosphatidylcholine (PC) in response to mastoparan. Despite the relative synthesis of higher levels of total and saturated PC in S- cells supplemented with linoleic acid, phosphatidylglycerol remained diminished. A surfactant protein (SP-A) was present in S- cells, but synthesis was not detected. These studies demonstrate that serum accelerates the loss of type II cell differentiation in vitro and that the expression of type II cell markers of differentiation is not inherently linked.

Animals↗
PubMed1990

Age at death: a three hospital urban, suburban, and small town study.

Comparison of the ages of patients dying at three interrelated St. Louis hospitals in 1988 has been used to study the results of similar high-quality acute hospital care when provided to dissimilar populations. The data presented by the authors leads them to conclude that in this era of mounting health costs, we have not, at least as recently as 1988, realized that an ounce of prevention if worth a pound of cure.

Adult↗
PubMed1988

The pattern of cytokeratin synthesis is a marker of type 2 cell differentiation in adult and maturing fetal lung alveolar cells.

During the last stages of fetal life, the immature epithelial cells of the rat lung alveolus develop the properties of mature type 2 cells. Adult type 2 cells rapidly lose these same properties when isolated and maintained in cell culture. We have examined the synthesis of cytokeratin proteins by adult type 2 cells as they lose their differentiated characteristics during 1 week in culture, and of immature fetal alveolar epithelial cells as they differentiate either in utero or when cultured on an extracellular matrix. Freshly isolated adult type 2 cells synthesize four cytokeratins which by electrophoretic mobilities and Western blot analysis correspond to human cytokeratins Nos. 7, 8, 18, and 19. During 7 days in culture synthesis of cytokeratin No. 19 is dramatically decreased and cytokeratin No. 18 becomes the predominant acidic cytokeratin produced. Fetal lung epithelial cells at 18 days gestation lack most characteristics of mature type 2 cells. When freshly isolated, these cells synthesize cytokeratins Nos. 7, 8, and 18 but make only minimal amounts of cytokeratin No. 19. When these cells are allowed to mature either in utero or in culture on a whole basement membrane extract, they develop both the morphological characteristics and the pattern of cytokeratin synthesis of fully developed type 2 cells, with cytokeratins No. 19 being the major acidic cytokeratin produced.

Animals↗
PubMed1986

Pulmonary rehabilitation for the elderly.

The elements of a pulmonary rehabilitation program require a variety of different skills. However, the number of people involved in a rehabilitation program will vary with the clinical setting and the number of patients served. In a large program, a physician, respiratory nurse, physical and occupational therapist, psychologist, social worker, respiratory therapist, and dietitian might all be involved on a full- or part-time basis. In other settings, two or three individuals, mostly working part-time, may be the entire team. Pulmonary rehabilitation may be performed on an outpatient basis, in a group practice setting, or in an inpatient hospital unit. Whatever its size, a system must be developed that allows for thorough initial evaluation of patients, formation of rational goals with the patient, adequate time for patient education and training, ongoing re-enforcement to consolidate and maintain gains, and an appropriate means of intervention when the patient experiences an exacerbation of his disease. It should also be recognized that in many areas of the country, there are too few patients and scarce medical resources to mount an intensive pulmonary rehabilitation program. In such instances, referral can be made to larger medical centers. More importantly, the individual practitioner can successfully incorporate many of the elements of pulmonary rehabilitation into his practice by taking the time and effort necessary to ascertain how illness affects the daily lives of the patient with COPD and then addressing patient concerns in an ongoing, comprehensive manner.

Activities of Daily Living↗
PubMedDate not supplied

Anterior cruciate ligament reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts. Two year results in thirty-six patients.

Thirty-six of 44 patients (82%) who underwent ACL reconstruction using freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts were evaluated at least 2 years postoperatively. A detailed subjective evaluation using the Lysholm scale was recorded as well as a functional evaluation using the Tegner activity scale. All of the patients received a detailed physical examination that included testing with the KT-1000 ligament arthrometer and the Cybex dynamometer. Complete chart reviews and radiographic evaluations were also obtained. Only 17 patients were considered to be functionally successful and performing at their desired activity level. The average KT-1000 showed a side-to-side difference of 5.9 mm at 30 pounds for the successful group and 7.9 mm for those who had functional failure. The Lysholm scores were 91.6/100 versus 61.1/100 in the failures. Eight patients (22%) at repeat surgery were noted to have complete dissolution of the graft. Large femoral cysts were noted radiographically in all of these patients. It was concluded that freeze-dried, ethylene oxide-sterilized, bone-patellar tendon-bone allografts have a high failure rate and cannot be recommended for ACL reconstruction.

Adolescent↗