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M Miller

Publications and source records attributed to M Miller.

At least 577 records · Page 32Linked to original sources
PubMed1989

Specificity and cross-reactivity of monoclonal antibodies reactive with the core and lipid A regions of bacterial lipopolysaccharide.

Twenty-nine murine monoclonal antibodies (MAbs) were prepared against antigenic determinants in the core and lipid A regions of Escherichia coli and Salmonella minnesota lipopolysaccharide (LPS). At least eight distinct MAb specificities were identified. Epitopes recognized by MAbs bearing these specificities were localized in the hexose, heptose, and 2-keto-3-deoxy-D-manno-octulosonic acid regions of the core oligosaccharide and on lipid A. Two groups of MAbs exhibited multispecificity for similar but distinct core- and lipid A-related epitopes. Some core-reactive MAbs cross-reacted with corresponding E. coli and Salmonella rough mutant chemotypes; others were specific for E. coli J5 LPS. Lipid A-specific MAbs reacted with free lipid A from diverse sources. Few MAbs reacted with smooth LPS. Antibody cross-reactivity was restricted by inter- and intraspecies differences in covalent core structure and by epitope concealment by overlying O-side chain and core sugars. The putative cross-reactive and antiendotoxic properties of MAbs specific for the core-lipid A complex may be limited by the inability of such MAbs to recognize determinants on "native" LPS.

Animals↗
PubMed1989

Lipopolysaccharide (LPS)-reactive monoclonal antibodies fail to inhibit LPS-induced tumor necrosis factor secretion by mouse-derived macrophages.

Murine monoclonal antibodies (MAbs) reactive with epitopes on the O-side chain, core oligosaccharide, or lipid A of Escherichia coli and Salmonella minnesota lipopolysaccharide (LPS) were evaluated for their ability to inhibit LPS-induced tumor necrosis factor (TNF) secretion by mouse-derived RAW 264.7 macrophages. As little as 50 ng of purified LPS or lipid A stimulated macrophages to produce TNF detectable as cytotoxic activity in an L-929 fibroblast assay. None of 13 MAbs (concentration range, 0.1-1,000 micrograms/mL) blocked LPS- or lipid A (0.025-0.1 micrograms/mL)-induced TNF secretion by RAW 264.7 cells. Rabbit antiserum to synthetic lipid A also failed to block lipid A-induced TNF activity. Similar negative results were obtained when intact bacteria or membrane vesicles were used as TNF inducers. In contrast, polymyxin B, but not the less hydrophobic polymyxin B nonapeptide, produced almost complete inhibition of macrophage TNF secretion induced by LPS, lipid A, membrane vesicles, and intact bacteria. Thus, antibody reactivity with predominantly hydrophilic elements of LPS or lipid A may not affect hydrophobic interactions between lipid A and target cell membranes necessary and sufficient for the induction of TNF. These findings raise doubts concerning the existence of true endotoxin-neutralizing antibodies.

Animals↗
PubMed1989

Atrial natriuretic peptides and tubular sodium handling during normal daily life in men.

The relationship between segmental renal tubular sodium handling (using the renal clearance of ingested lithium as a marker of proximal tubular sodium handling) and circulating plasma levels of atrial natriuretic factor (ANF) was studied in a sample of 295 untreated men drawn from a male population at work under their usual living conditions. Plasma ANF was positively and significantly related to sodium excretion at the distal nephron, indicating that this hormone interacts with a distal renal tubular site to influence the control of sodium excretion in man.

Adult↗
PubMed1989

xlgv7: a maternal gene product localized in nuclei of the central nervous system in Xenopus laevis.

The Xenopus oocyte nucleus (GV) is a storehouse for a large number of proteins that are used during early development. We have cloned and characterized a cDNA coding for a maternal gene product that is localized in the GV and then becomes highly enriched in the nuclei of the central nervous system (CNS) of tadpoles and adult frogs. This cDNA (xlgv7) is 2.1 kb and hybridizes to a 2.4-kb RNA species on Northern blots. Southern blots of genomic DNA suggest that this gene is a member of a multigene family. The cDNA sequence reveals a long open reading frame (ORF) of 1773 nucleotides, with a putative nuclear targeting signal (Glu Arg Arg Lys Lys Lys Thr) at the extreme carboxyl terminus and an internal histidine (His)-rich region with a repeated conserved amino acid sequence between His pairs. The significance of this region is unclear, but the protein is a DNA-binding protein, and it is possible that this region is involved in this function. The xlgv7 protein also possesses a putative nucleotide-binding consensus sequence that is similar to the bacterial RecA and RecB and yeast RAD proteins. Protein xlgv7 exists as several isotypes that exhibit developmental and cell-specific changes during development. Northern blot analysis of the abundance of the xlgv7 mRNA shows an accumulation following neural induction at stages 15-16. There is a transient expression of the mRNA in the gut of tadpoles. In the adult, the mRNA is highly enriched in the brain and is absent or in very low abundance in other tissues. Immunohistochemical analysis of the protein shows that the protein is localized in the nuclei of the brain cells. We conclude that the xlgv7 gene product is a maternal protein that may serve several important functions, one of which may be in the development and maintanance of the CNS.

Amino Acid Sequence↗
PubMed1989

Tolerance to cromakalim in the rat uterus in vivo.

1. Cromakalim (0.1 and 1 mg kg-1) produced inhibition of uterine contractions and falls in mean blood pressure in ovariectomized, non-pregnant rats, the durations of which were dose-dependent. Frequency of contractions was inhibited selectively compared to amplitude. 2. The durations of the uterine effect of cromakalim (1 mg kg-1), when given at 12 h intervals, were less after the second, third and fourth doses compared to the first dose in non-pregnant rats. In ovariectomized rats treated from day 18 of pregnancy, using the same experimental design, no uterine relaxant effects were seen to the third and fourth doses. The timing of delivery and foetal viability were unaffected by cromakalim. 3. The sensitivity of the uterus to cromakalim was tested using small doses before and after three cromakalim doses (1 mg kg-1) given at 8 h intervals in non-pregnant rats. This regime resulted in a 25 fold decrease in the sensitivity of the uterus to cromakalim. 4. Cromakalim can produce long-lasting inhibition of uterine contractions in the rat after bolus i.v. dose but it exhibits little selectivity relative to its vasodepressor action and there appears to be tolerance to the uterine relaxant action of cromakalim in vivo.

Animals↗
PubMed1989

Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine.

Determination of the effect of inotropic stimulation on regionally ischemic and hypokinetic myocardium is complicated when intravenous administration of the inotropic agent also causes stimulation of nonischemic adjacent and distant regions, thereby altering global ventricular hemodynamics. To obviate such events, 16 anesthetized swine were studied during regional inotropic stimulation by infusion of dobutamine hydrochloride (2.5 +/- 1 microgram/min) into the cannulated left anterior descending coronary artery. Coronary inflow was controlled by a pump in an extracorporeal circuit. Two groups of swine with different degrees of ischemia were studied. In the first group of animals (n = 8), reduction in coronary inflow to produce a fall in coronary artery pressure (CAP) from 114 +/- 7 mm Hg to 62 +/- 2 mm Hg caused a decrease in percent systolic wall thickening (%WTh) from 34.6 +/- 8.1% to 25.4 +/- 5.8% (p less than 0.005). In the second group of animals (n = 8), CAP was decreased to 46 +/- 5 mm Hg (control: 115 +/- 8 mm Hg) and % WTh decreased from 34.1 +/- 16.4% to 10.4 +/- 6.9% (p less than 0.001). Subendocardial blood flow was reduced from 1.41 +/- 0.38 ml/min/g to 0.65 +/- 0.13 ml/min/g (group 1, p less than 0.001) and from 1.08 +/- 0.22 ml/min/g to 0.24 +/- 0.08 ml/min/g (group 2, p less than 0.001). Regional infusion of dobutamine caused asynchronous ventricular contraction with early systolic augmentation in wall thickening followed by late systolic thinning. Therefore, during hypoperfusion regional myocardial function assessed by %WTh remained unchanged (26.2 +/- 5.8%, p = NS) in group 1 and decreased significantly to 1.6 +/- 5.1% (p less than 0.041) in group 2. Subendocardial blood flow decreased to 0.44 +/- 0.15 ml/min/g in group 1 (p less than 0.005) and to 0.15 +/- 0.07 ml/min/g in group 2 (p less than 0.012). To account for the augmented early systolic thickening that occurred during asynchronous contraction, a myocardial work index was developed in which the sum of the instantaneous left ventricular pressure-wall thickness product was calculated for estimation of regional myocardial work. Increases in this work index were apparent with the addition of dobutamine at both levels of hypoperfusion. This significant enhancement in regional myocardial function in group 2 caused a significant increase of 16% (p less than 0.009) in overall left ventricular power during ejection. Thus, regional inotropic stimulation with dobutamine caused enhancement of maximum work of the ischemic myocardium in the steady state despite a further decrease in subendocardial blood flow.

Animals↗
PubMed1989

Osteoclast-like cells form in long-term human bone marrow but not in peripheral blood cultures.

Transplantation studies have suggested that peripheral blood mononuclear cells contain precursors for osteoclasts. Thus we tested the capacity of peripheral blood monocytes to form osteoclasts in long-term culture. We have reported previously that mononuclear cells from feline, baboon, and human marrow form osteoclast-like cells in long term cultures. Further, the formation of these cells is increased in response to bone resorption stimulatory agents such as PTH, interleukin 1, and transforming growth factor alpha. We now report that these cells show characteristic cytoplasmic contraction with calcitonin and form resorption lacunae when cultured on sperm whale dentine. Thus, these bone marrow-derived multinucleated cells fulfill the functional criteria for osteoclasts. Although cultured peripheral blood monocytes can be induced to form multinucleated cells with 1,25-dihydroxyvitamin D3, these cells did not show similar responses to the osteotropic factors as multinucleated cells formed in the bone marrow cultures multinucleated cells. These results indicate that osteoclasts or cells closely related to osteoclasts form in long-term human bone marrow cultures. In contrast, few mononuclear cells in the peripheral blood appear capable of forming osteoclasts under the culture conditions used in these experiments.

Bone Marrow↗
PubMed1989

The maternal store of the xlgv7 mRNA in full-grown oocytes is not required for normal development in Xenopus.

We have attempted to analyze the function of a maternal mRNA xlgv7 which is distributed as an animal-vegetal gradient in stage 6 oocytes using a combination of antisense oligodeoxynucleotide injection into oocytes followed by in vitro maturation and fertilization. Injection of 20 ng of the antisense oligodeoxynucleotide resulted in the destruction of the xlgv7 mRNA to undetectable levels. Upon maturation and fertilization the resulting embryos develop with no specific defects suggesting that the maternal store of xlgv7 in stage 6 oocytes is not required and that the embryo can develop solely with the maternal store of the xlgv7 protein. Also, these results demonstrate the feasibility of this approach in destroying a specific maternal RNA and assaying its effect on development.

Animals↗
PubMed1989

Osteoclast-like cells formed in long-term human bone marrow cultures express a similar surface phenotype as authentic osteoclasts.

Long-term cultures of human bone marrow form multinucleated cells (MNC) with many functional characteristics of osteoclasts including: expression of tartrate-resistant acid phosphatase, appropriate responses to osteotropic hormones, calcitonin-induced contraction and formation of resorption lacunae on calcified matrices. However, it is unclear if these cells express similar surface antigens as expressed by authentic osteoclasts, since they form on plastic surfaces in the absence of bone. Bone may be required to complete the differentiation process for osteoclasts. Therefore, we have examined the surface phenotype of MNC and compared it with that of osteoclasts freshly isolated from bone, to determine if MNC express similar surface antigens, and if MNC express antigens which identify their cellular origin. Similar to bone-derived osteoclasts, MNC formed in long-term human bone marrow culture expressed osteoclast-specific antigens (detected by monoclonal antibodies 13c2 and 23c6) and did not express Fc receptors, T cell specific antigens, most myeloid antigens or mature macrophage antigens. In contrast to authentic osteoclasts, MNC reacted with a monoclonal antibody (Mol) which identifies an antigen present on myeloblasts, monocytes, granulocytes, and null cells from human peripheral blood and bone marrow. MNC also reacted with the monoclonal antibody My11, which is present on CFU-GM, the granulocyte-macrophage colony-forming cell, the probable precursor for MNC. These data demonstrate that MNC formed in long-term human marrow cultures express a similar surface phenotype to osteoclasts. This phenotype is different from that expressed by macrophage polykaryons. In addition, MNC also expressed monocyte-related antigens (My11, Mol), suggesting that are derived from or related to the monocytic lineage.

Animals↗
PubMed1989

Social approval for violations of sexual consent in marriage and dating.

This study compares approval for minor violations of sexual consent in three contexts: marriage, long-term dating, and a first date. Quantitative and qualitative data from a vignette experiment show that as couples progress from a first date to marriage, men gain support to violate their partner's consent, and, to a lesser degree, women lose support to assert their rights. Evidence is presented that men are more approving of male dominance and female passivity in dating and marriage than are women.

Adult↗
PubMed1989

Immune dysfunctions in psychiatric patients.

Alterations in the serum proteins and immunoglobulins have been investigated in the search for the possible etiological causes of schizophrenic patients. The results, so far, have been varied and inconclusive. We assayed serum immunoglobulins, and antinuclear antibody (ANA) titres in 94 randomly selected, recently hospitalized, psychotic patients. A complete physical, neurological, laboratory and electrophysiological examination was conducted on each patient. Systems survey and family, as well as past histories were obtained. Our results indicated that 12 patients had high titres of ANA and none of them had any other clinical evidence of autoimmune disease. This finding did not correlated with age, sex, diagnosis, or duration if illness, but an association with the medications that the patients were receiving, was noted. The elevation in ANA titres seems to be related to use of lithium as well as neuroleptics. Our data suggests that all neuroleptics can produce high ANA titres. Systematic study of this phenomenon and their long-term consequences warrant further exploration.

Adolescent↗
PubMed1989

Fusions and transfusions. An analysis of blood loss and autologous replacement during lumbar fusions.

Blood losses and transfusions have been analyzed prospectively for 63 lumbar fusion operations in 55 patients. The mean intraoperative loss was 550 ml, with a further 336 ml in postoperative drains. Factors increasing intraoperative loss included posterior vs. anterior approach, the use of instrumentation, multiple levels fused, male vs. female, and younger age. For anterior procedures (without instrumentation and using homograft bone) and single-level posterolateral fusions (PLF) without instrumentation, neither predeposit nor intraoperative salvage (cell saver) was required. Single-level PLF with instrumentation and two-level PLF without instrumentation required either cell saver or predeposit of one or two units. Multiple-level PLF with instrumentation and all 360 degrees procedures required cell saver and two units of predeposit. Two patients received homologous blood.

Adult↗
PubMed1989

Intraspinal narcotic analgesia. A comparison of two methods of postoperative pain relief.

Postoperative analgesia using continuous epidural morphine or a single intrathecal injection of morphine has been compared with standard patient-controlled analgesia (PCA) in lumbar fusion patients. Pain relief with epidural morphine was dramatic in some cases (3/12) but was not predictable, and catheter displacement was a frequent occurrence. A single intrathecal bolus of morphine had no advantage over PCA alone. Complications of both intraspinal techniques included nausea and pruritus. No respiratory depression was observed.

Adult↗