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Biomedical subjects

J A Hill

Publications and source records attributed to J A Hill.

At least 19 recordsLinked to original sources
PubMed1992

Relationship of anticoagulation and radiographic contrast agents to thrombosis during coronary angiography and angioplasty: are there real concerns?

Radiographic contrast agents are essential for the performance of coronary angiography and angioplasty. Historical data show that thrombosis-related events have occurred since coronary angiography has been performed. Newer non-ionic agents have been shown to be safer than conventional high osmolar ionic agents especially in high risk patients, but concern has been raised about a potentially increased risk of thrombosis with the use of these agents. A review of basic and clinical evidence for this perception does not support the view that an increase in thrombosis-related events has occurred as a results of non-ionic contrast media use in coronary angiographic procedures.

Angioplasty, Balloon, Coronary↗
PubMed1992

Matrix-assisted laser desorption using a fast-atom bombardment ion source and a magnetic mass spectrometer.

A conventional fast-atom bombardment (FAB) ion source was used to achieve matrix-assisted laser desorption (MALD) in a high-mass, double-focusing, magnetic mass spectrometer. The pulsed ion signals generated by irradiation of a mixture of sample and matrix (2,5-dihydroxybenzoic acid) with either a XeF excimer laser (353 nm) or a nitrogen laser (337 nm) were recorded with a focal-plane detector. A resolution (full-width at half maximum) of 4500 was achieved at m/z 1347.7 (the peptide substance P), 2500 for CsI cluster ions at m/z 10,005.7, and 1250 for the isotope cluster of the small protein cytochrome c (horse) [M+H]+ = m/z 12,360 (average). Sensitivity is demonstrated with 11 fmol of substance P. A survey scan is taken to locate the m/z of the sample molecular ion. The segment that contains the sample can then be integrated for a longer time to produce a better signal-to-noise ratio. In addition to higher sensitivity and lower matrix interference, the advantage of MALD over FAB is the former's lower susceptibility to the presence of salts, and competition between hydrophobic and hydrophilic components of a mixture. This feature is demonstrated by the complete MALD spectrum of a crude partial tryptic digest of sperm-whale apomyoglobin, containing 24 peptides, representing the entire sequence of this protein.

Animals↗
PubMed1992

Nicotinic receptor-associated 43K protein and progressive stabilization of the postsynaptic membrane.

An extrinsic membrane protein of apparent molecular mass 43 kDa is specifically localized in postsynaptic membranes closely associated with the nicotinic acetylcholine receptor (AChR). Since its discovery in 1977, biochemical and morphological studies have combined to provide relatively clear pictures of 43K protein structure and subcellular compartmentalization. Nevertheless, despite these advances, the precise function of this synapse-specific protein remains unclear. Data gathered in recent years indicate that the postsynaptic apparatus develops through the incremental agglomeration of receptor microaggregates; evidence derived from a number of sources points to a role for 43K protein in certain underlying reactions. In this paper, I review 43K protein structural and anatomical data and analyze evidence for its role in the organization and maintenance of the postsynaptic membrane. Finally, I offer a model presenting a view of the role of 43K protein in the ontogeny of the motor endplate.

Amino Acid Sequence↗
PubMed1992

Human vaginal leukocytes and the effects of vaginal fluid on lymphocyte and macrophage defense functions.

OBJECTIVES: The purpose of this study was to quantify, characterize, and further define the role of vaginal white blood cells in defense mechanisms and human immunodeficiency virus infection. STUDY DESIGN: Vaginal lavages were obtained from five healthy women throughout three menstrual cycles. Lymphocyte subpopulations, macrophages, and granulocytes were characterized and quantified by an immunohistologic technique. Vaginal lavage fluid was added to peripheral blood mononuclear cells, and effects on cell viability, lymphocyte proliferation, macrophage phagocytosis, and expression of various cell surface molecules critical to immunologic functions were assessed. Data were analyzed by Student's t test. RESULTS: Few lymphocytes were found at any stage of the menstrual cycle; however, granulocytes and macrophages were abundant at menstruation and present at low levels through the proliferative phase. Vaginal lavage fluid collected during menses, at midcycle, and after coitus suppressed mitogen-induced lymphocyte proliferation but had no effect on surface expression of human leukocyte antigen or CD4 antigens, or on macrophage function. Likewise, low pH (less than 5.0) medium significantly inhibited lymphocyte proliferation but had no effect on macrophage phagocytosis. The spermicide nonoxynol 9 was toxic to both lymphocytes and macrophages. CONCLUSION: White blood cells, including lymphocytes and macrophages, are infrequently present in cervicovaginal secretions of healthy women except during menses; the vaginal environment may effect their function.

Adult↗
PubMed1992

Acremonium infection in a neutropenic patient.

Acremonium species (previously Cephalosporium) are saprophytic moulds of low pathogenicity commonly found in the environment. We report a case of repeated acremonium fungaemia in a neutropenic patient, probably associated with a Hickman line. Fungaemia was accompanied by fever and a papular skin rash, both of which appeared to resolve when the neutrophil count recovered without antifungal chemotherapy, only to return when the patient next became neutropenic.

Acremonium↗
PubMed1992

Evidence of embryo- and trophoblast-toxic cellular immune response(s) in women with recurrent spontaneous abortion.

OBJECTIVE: The purpose of this study was to determine whether reproductive antigens stimulate lymphocytes and macrophages from women with recurrent abortion to secrete factors that are toxic to preimplantation embryos or trophoblast cells in vitro. STUDY DESIGN: Mononuclear cells were isolated from 30 fertile controls and 300 nonpregnant women being evaluated for recurrent abortion. Supernatants generated from these cells after separate culture with sperm and trophoblast antigen extracts were added to two-cell mouse embryo cultures and trophoblast proliferation assays. Toxicity was assumed when the median percentage of embryos developing to blastocysts or trophoblast proliferation was less than or equal to 50% of control values. Both parametric and nonparametric statistical methods were used where appropriate. RESULTS: Mouse embryo development and/or trophoblast proliferation were significantly inhibited by supernatants from trophoblast and/or sperm antigen-activated peripheral blood leukocyte cultures from a majority of 300 women with recurrent abortion but not from 30 women with normal reproductive histories. The mouse blastocyst development assay was more sensitive than the trophoblast proliferation assay in determining toxic factor production. Embryo-toxic factors were produced by activated leukocyte cultures from 90% of 180 women with a history of recurrent abortion of unexplained etiology, whereas trophoblast-inhibitory factors were detected in 50% of women from the same group. The embryo-toxic factor(s) was heat labile, had a molecular weight(s) between 10 and 30 kd, and was absorbed out by passage through affinity columns containing anti-interferon gamma beads. CONCLUSION: We conclude that recurrent abortion in some women is associated with embryo- and/or trophoblast-toxic factor production in response to stimulation by sperm or trophoblast antigens and that the principal factor may involve the 18 kd, heat-labile, T-lymphocyte cytokine interferon gamma. This study suggests a new cause of recurrent abortion.

Abortion, Habitual↗
PubMed1991

Serine-specific phosphorylation of nicotinic receptor associated 43K protein.

In Torpedo marmorata electroplaque, an extrinsic membrane protein of apparent mass 43,000 daltons colocalizes with the cytoplasmic face of the nicotinic acetylcholine receptor (AChR) in approximately 1:1 stoichiometry. We show that this 43K protein can be phosphorylated in vitro by endogenous protein kinases present in AChR-rich membranes. The extent of 43K protein phosphorylation exceeds that of the subunits of the AChR, well-established substrates for enzymatic phosphorylation. We demonstrate that significant 43K phosphoprotein exists in vivo. The kinetics of phosphate incorporation mediated by endogenous kinases differed significantly from those of the AChR subunits, suggesting that different phosphorylation cascades are involved. Use of specific inhibitors of a variety of protein kinases indicated that endogenous cAMP-dependent protein kinase catalyzes phosphorylation of the 43K protein in vitro. All of the phosphate incorporated into 43K protein was accounted for by phosphoserine (0.65 mol/mol of 43K protein). Potential structural and functional consequences of 43K protein phosphorylation are discussed.

Acetylcholine↗
PubMed1991

Effects of atenolol alone, nifedipine alone and their combination on ambulant myocardial ischemia.

The effects of atenolol (100 mg/day) and nifedipine (20 mg 3 times daily) and their combination on ambulant myocardial ischemia were investigated using a randomized, double-blind, placebo-controlled, crossover trial. Eighteen men with symptomatic coronary artery disease, exercise-induced ischemia and minimal symptoms, underwent 4 blinded treatment periods of 2 weeks' duration (2 placebo, 1 atenolol, 1 nifedipine). Those that did not have ischemia eliminated by monotherapy received combination therapy with both drugs. Forty-eight-hour ambulatory electrocardiographic monitoring was used to quantitate ischemic parameters at the end of each period. Both nifedipine and atenolol as monotherapy reduced the number of ischemic episodes and the average duration of each episode compared with placebo (p less than 0.05). Compared with placebo, nifedipine reduced the total duration of ischemia (p less than 0.05) but the effect of atenolol on ischemia duration was of borderline significance (p = 0.066). There were no differences in reduction of ischemic parameters when atenolol was compared with nifedipine (difference not significant). In the 9 patients who continued to have ischemia with monotherapy, combination therapy eliminated it in 2 and reduced the duration by greater than 50% in the remaining patients compared with placebo. In conclusion, monotherapy with nifedipine or atenolol is similarly effective in eliminating or reducing ambulant ischemia. Combination therapy can provide additional benefit in those with continued ischemia.

Adult↗
PubMed1991

The prognostic and economic implications of a strategy to detect and treat asymptomatic ischemia: the Atenolol Silent Ischemia Trial (ASIST) protocol.

Although silent ischemia may be linked to increases in cardiovascular morbidity and mortality, the long-term effects of a strategy aimed at the detection and treatment of this asymptomatic condition have not been fully explored. We therefore have developed the Atenolol Silent Ischemia Trial (ASIST), the first multicenter, randomized, prospective study of the prognostic implications of silent ischemia in asymptomatic and minimally symptomatic patients with coronary artery disease. Inclusion criteria for study patients were documented coronary artery disease, evidenced angiographically or by previous myocardial infarction, and transient ischemia, evidenced by abnormalities of regional wall motion, stress thallium-201, or exercise electrocardiogram. The main objective of ASIST is to assess the influence of frequency and duration of symptomatic and asymptomatic ischemic episodes on the occurrence of fatal and nonfatal cardiac events. Atenolol, a beta 1-selective adrenergic blocker, was chosen as the therapeutic intervention because of its potential benefits in treating both symptomatic and asymptomatic ischemia. Ambulatory electrocardiographic monitoring will be used to measure the frequency and duration of ischemic episodes during daily life. The predictive ability of short-term (4-week) effects on long-term (52-week) response to atenolol treatment is also being assessed, along with the economic impact of this diagnostic and therapeutic strategy. Given the current emphasis on reducing morbidity and mortality associated with coronary artery disease, ASIST results should shed light onto the long-term management and prognostic implications of this otherwise asymptomatic condition.

Atenolol↗
PubMed1991

Matrix-assisted laser desorption ionization with a magnetic mass spectrometer.

Matrix-assisted laser desorption ionization has been carried out with a high mass double-focusing magnetic mass spectrometer. The pulsed ion signal, generated by irradiation of the sample (substance P, ubiquitin, and cytochrome c) embedded in 2,5-dihydroxybenzoic acid with a XeF excimer laser (353 nm, 12 ns pulse, 10-160 Hz), was recorded with an integrating array detector. Good resolution of 2600 (full width at half maximum) and high sensitivity (a few pmol) were obtained. The loss of small neutral fragments was observed, supporting the notion that the peak broadening observed in the time-of-flight mass spectrometers commonly used for this ionization mode is due to such metastable decomposition.

Amino Acid Sequence↗
PubMed1991

The effects of soluble products of activated lymphocytes and macrophages on blastocyst implantation events in vitro.

The purpose of this study was to investigate the effects of soluble products of activated lymphocytes and macrophages on mouse blastocyst attachment and trophoblast outgrowth in vitro. Hatched blastocysts were incubated with medium alone, supernatant fluids from mixed lymphocyte cultures (MLC), and with individual human and murine lymphokines and monokines in fibronectin-coated wells. Cultures were assessed at 24, 48, and 72 h for blastocyst attachment and trophoblast outgrowth. Both human and murine MLC supernatant fluids significantly enhanced trophoblast outgrowth in vitro. The cytokine, interleukin-1 beta (Il-1 beta), at a concentration of 10(3) U/ml, inhibited blastocyst attachment but significantly enhanced trophoblast outgrowth of attached blastocysts. Granulocyte, macrophage-colony-stimulating factor (GM-CSF) at a concentration of 250 U/ml significantly inhibited blastocyst attachment, while gamma interferon (gamma-IFN) at a concentration of 2.5 x 10(3) U/ml significantly inhibited trophoblast outgrowth and caused degenerative morphological changes in these cells. The results of this study indicate that products of activated immune cells may either facilitate or impede implantation events depending on the types of predominant cytokines present, their concentration(s), and the timing of their secretion relative to embryonic development.

Animals↗