Search PubMed⌕ Search

Biomedical subjects

A Miller

Publications and source records attributed to A Miller.

At least 451 records · Page 25Linked to original sources
PubMed1988

Clinical experience with COP-1 in multiple sclerosis.

COP-1 is one of a series of polypeptide preparations developed to stimulate myelin basic protein (MBP), a natural component of the myelin sheath. MBP in Freund's complete adjuvant induces experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). In saline, MBP suppresses EAE. This is the rationale for the use of COP-1 in MS.

Adult↗
PubMed1988

Spirometric abnormalities among asbestos insulation workers.

We studied the prevalence of spirometric changes among asbestos insulation workers to investigate when functional abnormalities appear during the course of asbestos employment and the influence of cigarette smoking. Of 1,249 eligible asbestos insulation workers in the New York-New Jersey metropolitan area, 1,117 (89.4%) were examined in the year 1963 to provide baseline pulmonary function status for long-term prospective observation. Forced vital capacity (FVC) was measured in all 1,117 workers and forced expiratory volume in 1 second (FEV1) in 613 workers (55%). Of 353 workers examined in the first 10 years after onset of exposure, 26 (7.4%) had FVC below 70% of predicted, a prevalence similar to that reported in nonexposed general populations. Prevalence increased with time from onset of exposure. Of the 117 workers examined 40 or more years after onset of exposure, 76 (55%) had FVC below 70% of predicted. A similar trend with time was shown for FEV1 and FEV1/FVC. Cigarette smoking had little influence on the prevalence of pure restrictive impairment. Cigarette smokers and non-cigarette smokers had much the same prevalence (28%) of moderate to severe reduction of FVC while the FEV1/FVC was normal. None of the non-cigarette smokers and five of the cigarette smokers had a predominantly obstructive pattern. One non-cigarette smoker and eight cigarette smokers showed reduction of both FVC and FEV1/FVC, consistent with a mixed ventilatory abnormality. The data demonstrate that asbestos alone without the additional effect of cigarette smoking has no measureable effect on the function of the large airways.

Adult↗
PubMed1987

Effect of tumor necrosis factor alpha on mitogen-activated human B cells.

In this study we demonstrate that the monocyte/macrophage product, tumor necrosis factor alpha (TNF-alpha), has significant in vitro effects of B cell function. It costimulated with anti-mu in the induction of B cell DNA synthesis, and it prolonged the DNA synthesis initiated in B cell cultures stimulated with the human B cell mitogen, Staphylococcus aureus Cowan strain I (SAC). The addition of either IL-1 or IFN-gamma to TNF-alpha resulted in a substantial further increase in DNA synthesis. The addition of TNF-alpha to IL-2, a known inducer of SAC-activated B cell Ig secretion, resulted in a twofold enhancement in the amount of IL-2 stimulated B cell Ig secretion. Receptor binding studies with 125I-TNF-alpha demonstrate a marked increase in TNF-alpha binding sites after B cell activation (approximately 6,000 sites per cell, with an apparent Kd of 2.0 X 10(-10) M). Thus, TNF-alpha may be an important factor in human B cell function and is likely to interact with other T cell and monocyte derived cytokines in the regulation of human B cell proliferation and Ig production.

B-Lymphocytes↗
PubMed1987

A pilot trial of Cop 1 in exacerbating-remitting multiple sclerosis.

Cop 1 is a random polymer (molecular weight, 14,000 to 23,000) simulating myelin basic protein. It is synthesized by polymerizing L-alanine, L-glutamic acid, L-lysine, and L-tyrosine. It suppresses but does not induce experimental allergic encephalomyelitis, an animal model of multiple sclerosis. It is not toxic in animals. In a double-blind, randomized, placebo-controlled pilot trial, we studied 50 patients with the exacerbating-remitting form of multiple sclerosis, who self-injected either 20 mg of Cop 1 dissolved in 1 ml of saline or saline alone daily for two years. Six of 23 patients in the placebo group (26 percent) and 14 of 25 patients in the Cop 1 group (56 percent) had no exacerbations (P = 0.045). There were 62 exacerbations in the placebo group and 16 in the Cop 1 group, yielding two-year averages of 2.7 and 0.6 per patient, respectively. Among patients who were less disabled on entry (Kurtzke disability score, 0 to 2), there were 2.7 exacerbations in the placebo group and 0.3 in the Cop 1 group over two years. Among patients who were more affected (Kurtzke disability score, 3 to 6), there was an average of 2.7 exacerbations in the placebo group and 1.0 in the Cop 1 group. Over two years, less disabled patients taking Cop 1 improved an average of 0.5 Kurtzke units; those taking placebo worsened an average of 1.2 Kurtzke units. More disabled patients worsened by 0.3 (Cop 1 group) and 0.4 (placebo group) unit. Irritation at injection sites and rare, transient vasomotor responses were observed as side effects. These results suggest that Cop 1 may be beneficial in patients with the exacerbating-remitting form of multiple sclerosis, but we emphasize that the study is a preliminary one and our data require confirmation by a more extensive clinical trial.

Adult↗
PubMed1987

Functional reconstitution of the integral membrane proteins of influenza virus into phospholipid liposomes.

The integral membrane proteins of influenza virus, a hemagglutinin and a neuraminidase, have been incorporated into liposomes composed of either phosphatidylcholine or a mixture of phosphatidylcholine and phosphatidylethanolamine (2:1 w/w) using detergent dialysis. The virus spike glycoproteins for reconstitution were selectively solubilized by using cetyltrimethylammonium bromide to leave a "core particle", which lacked a lipid bilayer but possessed quaternary structure as observed by electron microscopy. The viral spike proteins were combined with exogenous phospholipid in excess sodium cholate followed by exhaustive dialysis for 150 h. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that only the viral glycoproteins were associated with all the complexes formed. The level of sodium cholate remaining after dialysis was shown to be reduced to less than 1 molecule per 80 protein molecules. Viral proteins reconstituted into dimyristoylphosphatidylcholine liposomes were shown to have retained hemagglutination, low-pH-dependent hemolysis, and neuraminidase activities and were associated with a lipid bilayer in two types of complexes with average lipid to protein mole ratios after sucrose density gradient purification of either 590:1 or 970:1. The bilayer vesicles formed were of similar sizes and were shown by negative-stain electron microscopy to be 150-300 nm in diameter with well-defined spikes on their surface. Reconstituted liposomes of dimyristoylphosphatidylcholine were found to be unstable with respect to their trapped volume and therefore were unsuitable for fusion studies, unlike complexes formed with phosphatidylcholine or a mixture of phosphatidylcholine/phosphatidylethanolamine derived from hen eggs.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimyristoylphosphatidylcholine↗
PubMed1987

Molecular packing in type I collagen fibrils.

Previous studies of the X-ray diffraction pattern of the crystalline regions of type I collagen fibrils yielded information on the unit cell parameters and also the orientation of the pseudo-hexagonally packed molecular segments in the overlap region. The absence of Bragg reflections at high angles attributable to the molecular segments in the gap region led to the suggestion that these segments were more mobile than those in the overlap region. We report a study of the low-angle Bragg reflections in a search for information about the nature of the orientation and packing of the molecular segments in the gap region. We conclude that the (m = 0, n = 0) helix layer plane of the molecular segments in the overlap region makes little or no contribution to the Bragg reflections at low angles, and identify three possible origins for the observed low-angle reflections in the electron density contrast associated with: (1) the "hole" created by the missing molecular segment in the gap region; (2) the telopeptides; or (3) the axial regularities in amino acid residues of a particular type, with periodicities of D/5 or D/6. Sufficient information is available to investigate the first two of these possibilities, and the results obtained suggest specific arrangements for the molecular segments in the overlap and gap regions, and specific connectivities between the molecular segments in successive overlap regions. In addition, we have examined the amino acid sequence and identified features related to the mobility of the molecular segments in the gap region and to the regions where it is thought that molecules are kinked.

Amino Acid Sequence↗
PubMed1987

The induction of helper and suppressor cells with secondary anti-hen egg-white lysozyme B hybridoma cells in the absence of antigen.

The results presented in this report define a dominant T cell-recognized public idiotype (SRId) expressed on monoclonal anti-chicken egg-white lysozyme (HEL) antibodies produced by hybridomas derived from secondary response lymphocytes. This Id mediates interactions between SRId+ B cells and SRId-recognizing T cells. In the absence of exogenous antigen, irradiated secondary anti-HEL B hybridoma cells (B-Hyb) of nonoverlapping specificity can be used to induce a helper T cell population capable of specifically stimulating an in vitro anti-HEL plaque-forming cell (PFC) response. Importantly, similar immunizations using carbodiimide-treated secondary anti-HEL B-Hyb cross-primed for a suppressor T cell population capable of suppressing this in vitro anti-HEL PFC response. That is, suppression was seen not only to the response induced by the homologous B-Hyb but to other B-Hyb which express anti-HEL monoclonal antibody of nonoverlapping specificity. This evidence is consistent with the presence of a pre-existent regulatory Id network involving SRId in antigennaive animals. After immunization with HEL, regulatory cells exert a strong selective pressure which leads to a secondary anti-HEL B population, of varying fine specificity, but uniformly positive for SRId.

Animals↗
PubMed1987

A phase II study of high-dose cytosine arabinoside in the treatment of acute leukaemia in adults.

Twenty-seven adults with refractory or recurrent acute leukaemia were treated with cytosine arabinoside (ara-C) 2 g/m2 infused over 3 h, every 12 h for 6 days, either alone (regimen A) or with vincristine and prednisolone (regimen B). Complete remission was achieved in 9/18 patients (5/12 regimen A, 4/6 regimen B) with acute lymphoblastic leukaemia (ALL), 1/7 patients (1/5 regimen A) with lymphoid blast crisis of chronic myeloid leukaemia (CML.LBC) and 1/2 patients (1/1 regimen B) with acute undifferentiated leukaemia (AUL). A further 5 patients (4 regimen A, 1 regimen B) with ALL, 4 patients (3 regimen A, 1 regimen B) with CML.LBC and 1 patient (regimen A) with AUL showed evidence of significant response. These results confirm the activity of high-dose a-ra-C in acute non-myelogenous leukaemia and suggest that it might be used with benefit to intensify the initial treatment of 'poor-risk' ALL.

Acute Disease↗
PubMed1987

Measurements of induced radioactivity in electron- and photon-irradiated beef.

Samples of beef were irradiated with electrons of approx. 10- and 13.5-MeV energies or with 60Co gamma-ray photons (1.17 and 1.33 MeV). Induced radioactivity was measured with a gamma-ray spectrometer, consisting of a Ge(Li) detector and a multichannel analyzer. No induced radioactivity could be detected in the photon-irradiated samples; also for 10-MeV electrons the activity was below the detection limit. The irradiation by 13.5-MeV electrons, however, resulted in measurable radioactivity and the amount of 13N-activity was in agreement with previously calculated values. These measurements confirm previous conclusions that irradiation of food with electrons at 10 MeV or even at 13.5 MeV does not constitute any health risk due to radioactivity. Part of the induced radioactivity from 13.5-MeV electron irradiation is due to neutron capture, and the results suggest that several neutron sources contribute to the measured radioactivity.

Animals↗
PubMed1987

In vitro maintenance of spermatogenesis in Xenopus laevis testis explants cultured in serum-free media.

Spermatogenesis has been maintained for extended periods in Xenopus laevis testis explants cultured in serum-free media supplemented with bovine serum albumin, insulin, transferrin, follicle-stimulating hormone, dihydrotestosterone, testosterone, retinol, ascorbate, and tocopherol. The organization of the testis fragments was maintained for 28 days, and all stages of development were present throughout the culture period. 3H-Thymidine-labeled secondary (Type B) spermatogonia developed in 28 days into spermatids at the acrosomal vesicle stage whereas labeled zygotene spermatocytes became mature spermatids in 28 days. Spermatogonial proliferation also continued in vitro for 28 days. Germ cell differentiation was not dependent upon exogenous testosterone, ascorbate, or tocopherol since 3H-labeled spermatogonia became mature spermatids in testes cultured 35 days in media lacking these supplements. Autoradiography demonstrated that 55% of the luminal sperm present in explants cultured 10 days had differentiated in vitro. Sperm from testes cultured 10-35 days were similar to sperm from freshly dissected testes with regard to motility and fecundity, and eggs fertilized with sperm from explant cultures developed normally into swimming tadpoles. The results demonstrate the feasibility of maintaining vertebrate spermatogenesis in culture and suggest that in vitro analysis of Xenopus spermatogenesis using defined media may provide important insights into the evolution of regulatory mechanisms in spermatogenesis.

Animals↗