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Biomedical subjects

R A Cooper

Publications and source records attributed to R A Cooper.

At least 199 records · Page 11Linked to original sources
PubMed1987

Effects of high energy particle (HZE) radiation on the distal lung.

Major sources of concern for manned space travel are the effects of high energy particle (HZE) radiation on various biological systems, and the consequences of major solar activity. To date, considerable attention has been directed toward HZE-induced alterations both on non-dividing systems, such as the retina, cornea and brain, and on dividing systems, such as the gut and testis. This paper is focused on the morphologically detectable late-occurring alterations in the distal lung, and toward a comparison of the changes with those induced by x-irradiation. Briefly, the salient alterations involve an increase in the width of the septal walls and the capillary and alveolar basal laminae, and the irregularity of the luminal surface of the capillaries, as exemplified by the presence of filipodial projections and blebbing. All alterations were focal in their localization, and no cells of any type (e.g., epithelial, endothelial or stromal) appeared to undergo damage, an observation quite unlike the cellular changes induced by x-irradiation.

Animals↗
PubMed1986

Transient modulation and internalization of T4 antigen induced by phorbol esters.

Phorbol esters are known to alter the expression of surface antigens and receptors on a variety of mammalian cell types. On T lymphoblastoid cell lines and peripheral blood T cells, phorbol esters have been shown to selectively reduce the expression of the T4 antigen. To more fully characterize this process, we have examined the metabolic requirements for this phorbol ester effect, and have evaluated the relationship between phorbol ester-induced T4 loss and the expression of receptors for phorbol-12,13-dibutyrate (PDB) on purified peripheral blood T4 cells. We observed that the loss of T4 on peripheral blood lymphocytes (PBL) occurred at PDB concentrations at which 10 to 15% of phorbol ester binding sites were occupied. The loss of T4 was inhibited at 4 degrees C, and by azide, methylamine, and sodium fluoride, but not by inhibitors of DNA synthesis. When cells were exposed to phorbol esters for greater than 2 days, the T4 antigen was again expressed on the cell surface despite the continued presence of phorbol esters. Cells which had recovered T4 were resistant to the effects of freshly added PDB on this antigen, and this resistance correlated with a 55% reduction in phorbol ester binding sites. Studies on fixed PBL T4 cells and MOLT-4 cells by immunofluorescence microscopy demonstrated that the decreased expression of T4 from the cell surface correlated with a bright clustering of T4 within the cytoplasm, indicating that PDB had induced an internalization of this antigen. These observations demonstrate that the binding of phorbol esters to specific receptors on lymphocytes initiates metabolically dependent events which result in the internalization of the T4 antigen. These findings may be relevant to mechanisms by which T4 functions as a signal-transducing molecule in vivo.

Adult↗
PubMed1986

Value of two-dimensional echocardiography, electrocardiography, and clinical signs in detecting right ventricular infarction.

Noninvasive tests for the diagnosis of right ventricular (RV) infarction--two-dimensional echocardiography (2DE), ST elevation in V4R, and clinical parameters--were compared with equilibrium gated blood pool study (GBPS) in 50 patients after acute inferior myocardial infarction. Twenty-two of 50 patients had RV wall motion abnormalities on GBPS and 20 of 50 on 2DE. Sensitivity and specificity of 2DE was 82% and 93%, ST elevation in V4R was 50% and 71%, elevation of venous pressure was 77% and 85%, and a positive Kussmaul's sign was found in 59% and 89% for the detection of RV infarction compared to GBPS. Patients with RV infarction had higher peak creatine kinase levels and lower left ventricular ejection fractions than patients without RV infarction. Three patients died and all had significant left ventricular damage. At 20 weeks' follow-up, two thirds of the patients had no residual RV wall motion abnormalities, and all but two patients showed some recovery.

Adult↗
PubMed1986

RNA-DNA hybridization analysis of transcription of the plasmid ColV-K30 aerobactin gene cluster.

Plasmid pABN1 contains the genetic determinants for the aerobactin iron uptake system of plasmid ColV-K30. Transposon Tn1000 mutants of pABN1 defective in synthesis of a 50,000-dalton polypeptide were found neither to secrete nor to accumulate aerobactin, but were not impaired in iron transport functions, clearly indicating a role for this polypeptide in aerobactin biosynthesis. RNA-DNA hybridization studies with probes spanning the entire aerobactin gene cluster showed that the system is regulated at the transcriptional level by the availability of iron in the external medium. When induced by low-iron stress, all five genes of the cluster were transcribed at a uniformly high level. When repressed by excess iron, transcripts of the four biosynthesis genes were some 30-fold less abundant in the case of the parental ColV-K30 plasmid and 10-fold less for the recombinant plasmid pABN1, whereas the receptor gene in either plasmid was transcribed at only about a third of the induced level.

Bacterial Outer Membrane Proteins↗
PubMed1986

Long term effects of radiation and combined modalities on mouse lung.

The lung appears to be the major dose-limiting organ in radiation of the thorax. Early responses (less than 1 week) involve the type II pneumocyte and increased surfactant biosynthesis and secretion. Later changes, which appear to be related to the surfactant response, lead to classical radiation pneumonitis, which is often fatal. Animals which survive radiation pneumonitis develop progressive fibrosis, a late-appearing response, which reduces compliance and available air space, and is usually fatal. This study centers on the fine structural changes in the lungs of LAF1 mice, 63 weeks following various radiation exposures (5-13 Gy). Doses which are subthreshold in evoking surfactant and pneumonitic responses precipitate fibrosis and atelectasis by 63 weeks, and involve type II pneumocyte sloughing and degeneration. Of the two major deterrents to lung irradiation (pneumonitis and fibrosis), these results suggest that fibrosis always follows pneumonitis, but pneumonitis is not a necessary preliminary step to fibrosis. Bleomycin elicits several morphological alterations characteristic of radiation, and, when combined with the latter, appears to exacerbate radiation effects.

Animals↗
PubMed1986

Differential effects of phorbol esters on normal myeloid precursors and leukemic cells: basis for autologous bone marrow reconstitution in acute nonlymphocytic leukemia using phorbol ester-treated bone marrow from patients in remission.

The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) induces macrophage-like differentiation of HL60 cells and cells from patients with acute nonlymphocytic leukemia (ANLL). We assessed the use of TPA as a means of eradicating residual leukemia from remission bone marrow prior to autologous bone marrow reconstitution. A 30-min incubation with TPA led to marked growth arrest in HL60 cells and in cells from most patients with acute myelogenous leukemia and acute myelomonocytic leukemia, whereas cells from most patients with acute promyelocytic leukemia and acute undifferentiated leukemia demonstrated a lesser degree of growth arrest. Freezing and thawing, a necessary step in autologous reconstitution, had no effect on the cessation of proliferation induced in HL60 or ANLL cells preincubated with TPA for 30 min. Virtually normal myeloid precursor growth occurred in normal or remission bone marrow cells preincubated with TPA and then frozen and thawed. Based on these observations, two patients with advanced ANLL in remission underwent marrow ablative therapy followed by autologous reconstitution using TPA-treated bone marrow. Limited normal hematopoiesis was reestablished in both patients, although they subsequently experienced leukemic relapse. These studies demonstrate that in ANLL cells, TPA stimulates growth arrest; in contrast, hematopoiesis is able to proceed both in vitro and in vivo.

Bone Marrow↗
PubMed1985

The growth and morphology of FRTL-5 thyroid epithelial cells grown as multicellular spheroids in vitro.

FRTL-5 cells, a diploid line of differentiated rat thyroid epithelial cells, have been grown as multicellular spheroids in spinner culture. Spheroids were initiated by seeding FRTL-5 cells either into Lab-Tek dishes or culture flasks with a 0.5% agar base. Thyroid stimulating hormone (TSH, greater than 1.0 mU/ml) was required for initial cell aggregation and spheroid growth. After 1 wk cellular aggregates were transferred to suspension culture in spinner flasks. As with FRTL-5 monolayer cultures, continued spheroid growth required the addition of TSH to the culture medium. The most unique characteristic of the FRTL-5 spheroids was the development of central lumina similar to thyroid follicles in vivo. Follicular structures were absent from spheroids not stimulated with TSH. In the presence of TSH epithelial cells seem metabolically active with morphological evidence of biosynthesis of thyroglobulin-like material and basal laminar-like components. In contrast, all evidence of cellular metabolic activity is absent from cells in spheroids maintained in the absence of TSH. Thus, nontransformed FRTL-5 cells grown as three-dimensional multicellular spheroids responded to hormonal manipulation in a manner comparable to follicular epithelial cells in vivo. This spheroid model might therefore prove to be a very effective tool for investigating aspects of thyroid physiology and pathology in vitro.

Animals↗
PubMed1984

Myelopoiesis following phorbol ester exposure in human long-term bone marrow cell culture.

Phorbol esters have two opposing effects on bone marrow granulocyte/macrophage colony forming cells (CFC-GM): they reduce the number of CFC-GM which respond to colony-stimulating activity (CSA), and they also induce the release of CSA from accessory marrow cells. We questioned whether the direct inhibitory effect of phorbol esters on CFC-GM was reversible and whether phorbol ester-treated accessory bone marrow cells could increase the in vitro recovery of cultured CFC-GM. Normal human bone marrow cells were exposed to phorbol-12,13-dibutyrate (PDB) for 5 days in liquid cultures. Total nucleated cell counts decreased in a dose-dependent fashion to 42 +/- 6% of control at 5 X 10(-8) M PDB, and CFC-GM decreased to 20 +/- 8% of control. The cultures were then washed to remove PDB and continued for up to 8 weeks. Total cell counts and CFC-GM/ml remained reduced in PDB-pretreated cultures compared to control. To determine whether this was a direct effect of PDB on nonadherent, proliferating cells or whether PDB acted indirectly by affecting adherent, accessory cells, nonadherent bone marrow cells from control and PDB-preincubated cultures were co-cultured for 8 weeks with either control or PDB-preincubated adherent bone marrow cells. Nonadherent cells preincubated with PDB had a similar growth pattern whether or not the co-cultured adherent cells had been preincubated with PDB. In contrast, nonadherent cells preincubated in control medium and co-cultured with PDB-preincubated adherent cells displayed increased numbers of nucleated cells, CFC-GM and adherent hematopoietic islands compared to control. This was associated with increased amounts of CSA present in the culture supernatants. Thus PDB causes an irreversible decrease in CFC-GM in long term marrow cultures but enhances the ability of adherent stromal cells to support normal CFC-GM growth in culture.

Bone Marrow↗
PubMed1984

Review of the overall experience of captopril in hypertension.

The pharmacologic profile of the angiotensin-converting enzyme inhibitor, captopril, is described. After reviewing the total clinical experience of captopril from the world literature and manufacturer's files, a small subgroup of clinically complex patients at particular risk of side effects and in whom the drug must be used with caution is characterized. Evidence is available that demonstrates that lower doses (150 mg/day or less, with modest doses of diluretic agents) are effective in both short- and long-term therapy, while the incidence of side effects is substantially reduced. With this background information, the benefit-risk ratio is substantially improved and the use of captopril as a primary agent in the management of hypertension may be considered.

Captopril↗
PubMed1984

Release of granulocyte-specific colony-stimulating activity by human bone marrow exposed to phorbol esters.

Granulocyte-macrophage colony growth depends on the presence of colony-stimulating activity (CSA). Phorbol esters induce concentration-dependent colony formation in the absence of exogenous CSA. We questioned whether phorbol esters mimicked the action of CSA by directly stimulating colony growth, or whether phorbol esters acted indirectly by inducing marrow cells to release CSA. First, after incubating human bone marrow cells with phorbol 12,13-dibutyrate (PDB) for 3 days, we separated PDB from the protein peak of the conditioned medium by Sephadex G-10 gel filtration and tested this peak for the presence of CSA. When diluted 1:10 in the agar colony assay, this material induced 133 +/- 15 colonies/10(5) bone marrow cells. Second, to determine whether bone marrow cells required the continued presence of PDB in order to release CSA, PDB was removed from bone marrow cells by washing, and these cells were reincubated in fresh medium in the absence of PDB. CSA was found in the medium of these cultures; its release was maximal after preincubation of bone marrow cells with 5 X 10(-8) M PDB for 3 days, followed by incubation for 3 days in the absence of PDB. This CSA stimulated granulopoiesis out of proportion to monocytopoiesis, with 85% +/- 17% of the colonies being granulocytic (as indicated by histochemical staining for chloroacetate esterase), and 12% +/- 3% being monocytic (as indicated by nonspecific esterase). Inhibitors of monocyte colony formation, including PGE1, were not present in the medium that contained this CSA. These studies demonstrate that normal human bone marrow cells exposed to PDB release CSA and that this CSA selectively stimulates granulopoiesis in vitro.

Alprostadil↗
PubMed1983

Evidence for two distinct pyruvate kinase genes in Escherichia coli K-12.

A strain of Escherichia coli K-12 defective in pyruvate kinase F has been produced. The existence of this mutant, in conjunction with earlier results, strongly suggests that the two pyruvate kinases in this bacterium are distinct forms and not interconvertible. Either form of pyruvate kinase appeared to be equally effective in the glycolytic conversion of phosphoenolpyruvate to pyruvate. Genes specifying pyruvate kinase A and pyruvate kinase F were present on the small F-prime F506 and the locus for pyruvate kinase F was found to be at minute 36.5 on the E. coli genetic map.

Chromosome Mapping↗
PubMed1983

Dissolution of renal calculi with dicloxacillin.

A patient with multiple left renal calculi and Staphylococcus epidermidis urinary tract infection is described. Subsequent treatment consisted of dicloxacillin which resulted in complete dissolution of all renal calculi. The rationale, supporting data, and potential therapeutic uses are reported.

Adolescent↗
PubMed1983

Fertility rate after hysterosalpingography with Sinografin.

Patients undergoing diagnostic hysterosalpingography because of infertility often become pregnant soon after the procedure. Since the discontinuation of Salpix in March 1980, the use of Sinografin for hysterosalpingography has increased. The pregnancy rate after hysterosalpingography using Sinografin has never been reported, however, and now 156 such patients have been evaluated. The pregnancy rate was 10.9% in those who had only a hysterosalpingogram and 26.3% in those who received adjunctive therapy. These results are comparable to those previously reported for hysterosalpingography using water-soluble contrast material, but less than the results using oil-soluble contrast.

Contrast Media↗