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M J Miller

Publications and source records attributed to M J Miller.

At least 19 recordsLinked to original sources
PubMed1992

Long-term results of directional coronary atherectomy: predictors of restenosis.

OBJECTIVES: This study was performed to obtain better understanding of the long-term clinical efficacy of directional coronary atherectomy. BACKGROUND: Although this procedure yields favorable acute results, its acceptance has been limited by the perception that late results (that is, freedom from restenosis) are no better than those of conventional angioplasty. METHODS: A total of 225 atherectomies performed in 190 patients between August 1988 and July 1991 were examined. Minimal lumen diameter of the treated segments was measured on angiograms obtained before, after and 6 months after intervention. RESULTS: Although most lesions (97%) had one or more characteristics predictive of unfavorable short- or long-term results after conventional angioplasty, atherectomy was successful in 205 lesions (91%) with a mean residual stenosis of 7 +/- 16%. After subsequent balloon angioplasty in 16 unsuccessful atherectomy attempts, procedural success was 98%. There were no deaths or Q wave myocardial infarctions, and one patient (0.5%) underwent emergency bypass surgery. Six-month angiographic follow-up was obtained in 77% of the eligible patients. The overall angiographic restenosis rate was 32%. Predictors of a lower restenosis rate included a postprocedure lumen diameter > 3 mm (24% vs. 39%, p = 0.047), serum cholesterol < or = 200 mg/dl (18% vs. 40%, p = 0.018) and recent myocardial infarction (16% vs. 37%, p = 0.034). Life-table analysis showed a 2% mortality rate and a 26% incidence of other events (myocardial infarction, repeat revascularization) within the 1st year. The annual 5% mortality rate and 7% incidence of other events during years 2 and 3 were related in large part to the existence or progression of disease at other locations. CONCLUSIONS: Six-month angiographic follow-up of patients who underwent directional coronary atherectomy during the 1st 3 years of our experience shows an overall restenosis rate of 32%, with lower rates in patients with a postatherectomy lumen diameter > or = 3 mm, cholesterol level < or = 200 mg/dl or a recent myocardial infarction. Few if any events relating to the site of atherectomy developed after the 1st year of follow-up.

Atherectomy, Coronary↗
PubMed1992

Quantitative two-dimensional gel electrophoresis analysis of human fibroblasts transformed by ras oncogenes.

Quantitative two-dimensional gel electrophoresis was used to compare the cellular protein patterns of a normal foreskin-derived human fibroblasts cell line (LG1) and three immortal derivatives of LG1. One derivative, designated MSU-1.1 VO, was selected for its ability to grow in the absence of serum and is non-tumorigenic in athymic mice. The other two strains were selected for focus-formation following transfection with either Ha-ras or N-ras oncogenes and form high grade malignant tumors. Correspondence and cluster analysis provided a nonbiased estimate of the relative similarity of the different two-dimensional patterns. These techniques separated the gel patterns into three distinct classes: LG1, MSU-1.1 VO, and the ras transformed cell strains. The MSU-1.1 VO cells were more closely related to the parental LG1 than to the ras-transformed cells. The differences between the three classes were primarily quantitative in nature: 16% of the spots demonstrated statistically significant changes (P < 0.01, T test, mean ratio of intensity > 2) in the rate of incorporation of radioactive amino acids. The patterns from the two ras-transformed cell strains were similar, and variations in the expression of proteins that occurred between the separate experiments obscured consistent differences between the Ha-ras and N-ras transformed cells. However, while only 9 out of 758 spots were classified as different (1%), correspondence analysis could consistently separate the two ras transformants. One of these spots was five times more intense in the Ha-ras transformed cells than the N-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Transformation, Neoplastic↗
PubMed1992

Rabbit gut permeability in response to histamine chloramines and chemotactic peptide.

Granulocyte-derived chlorinated amines and bacterial formyl peptides are thought to enhance epithelial permeability. In the current study, gut permeability to [51Cr]ethylenediaminetetraacetic acid (EDTA) was monitored in response to luminal formyl-methionyl-leucyl-phenylalanine (fMLP) and histamine monochloramine and dichloramine. Responses were determined in rabbits during states of basal and elevated permeability. Luminal fMLP had minimal effects of gut permeability in control and injured states. Histamine monochloramine or dichloramine enhanced epithelial permeability under basal conditions; this effect was exaggerated by a pre-existing injury. Both histamine monochloramine and dichloramine retained full histamine agonist properties, and a combination of antioxidant and antihistamine therapy was required to block this increase in gut permeability. Whereas histamine chloramines caused a dose-dependent cytotoxicity in rat-cultured enterocytes, marked histological changes to the mucosa were not evident, nor were mucosal glutathione levels depleted. As histamine chloramines retain the histaminergic and oxidizing potential of their precursors, they represent a unique form of inflammatory mediator, although their highly reactive nature precludes in vivo confirmation of their formation.

Animals↗
PubMed1992

Comparison of the rectus abdominis free flap with the pectoralis major myocutaneous flap for reconstructions in the head and neck.

The pectoralis major myocutaneous flap (PMMF) is often used in the reconstruction of large head and neck defects. Unfortunately, its use is associated with a high incidence of minor complications, can distort the contour of the neck, and may cause significant donor site deformity, especially in women. This study compared 30 patients with major head and neck cancer-related defects who underwent reconstruction with a rectus abdominis free flap (RAFF) with 39 patients with similar defects who underwent reconstruction with the PMMF. The complication rate found in the RAFF group (13%) was significantly lower than that found in the PMMF group (44%; p = 0.0145). Flap necrosis was found in 10% of the PMMF group, whereas none was found in the RAFF group. The aesthetic outcome was also better in patients who had reconstructions with the RAFF. We conclude that, for most major head and neck defects, reconstruction methods that utilize the RAFF and other free tissue transfer techniques are preferable when the requisite equipment and expertise are available.

Abdominal Muscles↗
PubMed1992

Modes of action and inhibitory activities of new siderophore-beta-lactam conjugates that use specific iron uptake pathways for entry into bacteria.

We describe here the mechanism of inhibition of two new siderophore-beta-lactam conjugates against Escherichia coli X580. One conjugate is a spermidine-based catechol siderophore-carbacephalosporin (JAM-2-263), and the other is an N5-acetyl-N5-hydroxy-L-ornithine tripeptide hydroxamate siderophore-carbacephalosporin (EKD-3-88). In an agar diffusion test, both conjugates produced large inhibitory zones against strain X580. Resistant strains (i.e., JAMR and EKDR) could be isolated after exposure of X580 to the conjugates JAM-2-263 and EKD-3-88, respectively. No cross-resistance was observed in these individual isolates. JAMR and EKDR were studied further to elucidate the mechanism of inhibition of each conjugated drug. The affinities of JAM-2-263 and EKD-3-88 for penicillin-binding proteins (PBPs) of isolated inner membranes were determined by a competition assay with 125I-penicillin V. JAM-2-263 targeted primarily PBPs 1A/B and 5/6, while EKD-3-88 targeted PBPs 1A/B and 3. Strains X580, JAMR, and EKDR showed similar PBP affinities for the conjugates. However, marked changes were observed in the iron-regulated outer membrane proteins of resistant isolates grown on agar plates depleted of iron. EKDR lost the expression of FhuA (78 kDa) and its sensitivity to phages T1 and T5, whereas JAMR lost the expression of Cir (74 kDa) and its sensitivity to colicin Ia. These results revealed the requirement of FhuA and Cir for the inhibitory activities of EKD-3-88 and JAM-2-263, respectively. In an antibiotic diffusion assay, ferrichrome (1 microM) strongly antagonized the activities of both conjugates against X580 and JAMR, including the residual activity of JAM-2-263 against JAMR. However, the susceptibility of strain EKDR lacking the ferrichrome receptor (FhuA-) to the two conjugates remained the same in the presence of ferrichrome. The antagonistic effect of ferrichrome on the activity of JAM-2-263 may also indicate a role for FhuA in the activity of this beta-lactam conjugate. A FhuA- Cir- double mutant confirmed this hypothesis, since it showed a higher level of resistance to JAM-2-263. To reproduce iron-restricted in vivo growth conditions, we grew X580 and EKDR cells in diffusion chambers implanted in the peritoneal cavities of rats. Strain EKDR showed impaired growth in such a cultivation system. This is the first report of beta-lactam drug transport into E. coli cells that involves the FhuA outer membrane protein.

Animals↗
PubMed1992

Iron transport-mediated antibacterial activity of and development of resistance to hydroxamate and catechol siderophore-carbacephalosporin conjugates.

Peptides containing residues of N5-acetyl-N5-hydroxy-L-ornithine were evaluated as potential artificial siderophores of beta-lactam-hypersusceptible Escherichia coli X580. Only those peptides which were capable of forming a hexadentate complex around ferric iron, which is analogous to the natural siderophore ferrichrome, were able to reverse the growth inhibition effects of the ferric iron chelator ethylenediamine di(o-hydroxyphenylacetic acid). A synthetic bis(catechol) spermidine derivative, similar to the natural siderophores enterobactin and agrobactin, also exhibited siderophore activity with this strain. Conjugation of the N5-acetyl-N5-hydroxy-L-ornithine tripeptide and the bis(catechol) siderophore to the potent carbacephalosporin loracarbef and closely related analogs provided compounds which exhibited antibacterial activity against E. coli X580. As was observed with the naturally occurring albomycins, the initial bactericidal effect was followed by the appearance of survivors that were resistant to the test compound. An enhanced killing effect was observed when the parent was incubated simultaneously with hydroxamate and catechol siderophore-antibiotic conjugates. Natural and synthetic siderophore growth promotion experiments with survivors resistant to the conjugates strongly suggested that disabled ferrichrome and enterobactin-catechol assimilation mechanisms may be responsible for the observed resistance. One isolated survivor was postulated to be a tonB mutant. The antibacterial activities of the described siderophore-carbacephalosporin conjugates appear to be related to an iron transport assimilation mechanism and would not have been detected during routine MIC testing procedures.

Catechols↗
PubMed1992

Tracheal smooth muscle responses to substance P and neurokinin A in the piglet.

The tachykinins substance P (SP) and neurokinin A (NKA) have been shown to induce airway smooth muscle contraction in mature animals, and the enzyme neutral endopeptidase (NEP) modulates this effect. We evaluated maturation of SP- and NKA-induced tracheal smooth muscle contraction and modulation of their effects by NEP in anesthetized, paralyzed, and artificially ventilated piglets less than 4 days, 2-3 wk, and 10 wk of age. Tracheal smooth muscle tension was measured in vivo from an open tracheal segment by use of a force transducer. Intravenous SP caused a dose-dependent increase in tracheal tension in all three age groups; however, the response in less than 4-day-old piglets was significantly weaker than in 2- to 3- and 10-wk-old piglets. NKA caused a dose-dependent increase in tracheal tension only in 2- to 3- and 10-wk-old piglets. The response of tracheal tension to NKA was weaker than the response to SP in all age groups. Atropine (2 mg/kg) significantly diminished the responses of tracheal tension to SP and NKA, indicating a cholinergic contribution to these responses at all ages. Intravenous thiorphan, a known NEP inhibitor, potentiated the effects of SP only in 2- to 3- and 10-wk-old piglets and did not affect the response of tracheal tension to NKA at any age. Biochemical analyses demonstrated a significant increase in tracheal NEP activity in comparably aged piglets over the first 10 wk of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Alae nasi activation in preterm infants during oral feeding.

Preterm infants may demonstrate impaired ventilation during oral feeding with resultant hypoxemia and hypercarbia. This study was designed to determine whether infants activate a representative upper airway muscle, the ala nasi, in response to these ventilatory changes. Ten preterm infants (postconceptional age at study 35 +/- 4 wk, weight 2.2 +/- 0.1 kg) were studied during a control period, continuous feeding, subsequent intermittent feeding, and a period of nonnutritive sucking. Nasal airflow was measured with a pneumotachometer to quantify minute ventilation. The alae nasi electromyogram (EMGAN) was recorded with surface electrodes, and sucking pressure was detected by a catheter in the feeding nipple. End-tidal CO2 and O2 saturation were also recorded during each period. The percentage of breaths associated with EMGAN activity increased from 41 +/- 13% during the control period to 95 +/- 5% and 93 +/- 7% during continuous and intermittent sucking, respectively (p < 0.05). Eighty-seven +/- 5% of EMGAN activity occurred during inspiration. During continuous and intermittent sucking, the amplitude of EMGAN activity also increased (6.8 +/- 5.2 and 6.7 +/- 4.0 arbitrary units/breath, respectively) compared with the control period (2.4 +/- 2.8 units/breath, p < 0.05). In association with the increase in EMGAN activity, O2 saturation fell from 98 +/- 1% in the control period to 95 +/- 1% during both continuous and intermittent feeding (p < 0.05), and minute ventilation fell from 274 +/- 80 mL/min/kg during the control period to 190 +/- 81 and 208 +/- 57 mL/min/kg during continuous and intermittent feeding, respectively (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon Dioxide↗
PubMed1992

The osteocutaneous free fibula flap: is the skin paddle reliable?

This clinical and anatomic study was undertaken to see if the skin paddle of the osteocutaneous fibula flap could be made more reliable. Eighty cadaver limbs were dissected to evaluate the type, number, and location of the cutaneous perforators supplying the lateral leg. Three types of perforators were identified: septocutaneous, musculocutaneous, and a type we termed septomuscular, which does not actually run within the muscle substance but is adherent to the muscle. Although not a true musculocutaneous perforator, it should be treated as such clinically. Musculocutaneous perforators were found to be more numerous and more proximal than the septocutaneous perforators. Eighteen clinical cases demonstrate a 33 percent skin paddle survival when dissected as a septocutaneous flap and a 93 percent skin paddle survival when dissected as a septomusculocutaneous flap. In using the osteocutaneous fibula flap, it is recommended that a cuff of soleus and flexor hallucis longus be incorporated into the flap to help ensure flap viability.

Bone Transplantation↗
PubMed1992

Apnea of prematurity.

Apnea is a common, treatable disorder of respiration in premature infants, which usually resolves over time. The definition and classification of apnea are discussed, as well as its epidemiology and natural history. The pathophysiology of apnea is considered in detail, including the chemosensory and reflex input that modulates respiration and the involvement of upper airway control in the etiology of obstructive apnea. Finally, diagnosis and therapy are reviewed, and the relationship of apnea of prematurity to the underlying disorder in sudden infant death syndrome is considered.

Apnea↗
PubMed1979

Quantitative analysis of two-dimensional electrophoretograms.

A method for quantitative analysis of complex film density distributions in autoradiograms is described. The method is intended particularly for measuring the distribution of radioactivity among the proteins resolved by two-dimensional gel electrophoresis but should, of course, be suited to analyzing other two dimensional separations. The film density distribution is first digitized by a high speed rotating drum scanner to generate the image data array that is stored on a magnetic disk. Subsequent analysis involves: 1) data averaging, 2) detection of contours and of their locations, 3) splitting of overlapping spots, 4) conversion of film density to radioactive intensity by means of calibration films, and 5) differentiation and integration to measure the total radioactivity contained in the protein which generates a spot in the autoradiogram. The product of the analysis is a numbered contour map and a table listing coordinates and radioactivity content of each resolved spot. Coordinate transformations for comparison and matching of autoradiograms are also described. A set of utility programs print and graph the data at intermediate stages of the analysis in order to facilitate the checking of procedures and programs.

Autoradiography↗
PubMed1979

A response of protein synthesis to temperature shift in the yeast Saccharomyces cerevisiae.

When Saccharomyces cerevisiae are subjected to a sudden increase in temperature (22 degrees C to 37 degrees C) they undergo extensive and, in some cases, extreme alterations in their rates of synthesizing individual polypeptides. These changes were monitored by pulse-labeling cells with [35S]methionine and separating the total soluble proteins by two-dimensional gel electrophoresis. Incorporation of 35S into individual proteins was measured by a computer-coupled autoradiogram-scanning method. The rates of synthesis of most proteins are transiently changed; 10-fold or greater induction or respression is common. This temperature response has also been studied in a mutant strain that is temperature sensitive for the nucleus-to-cytoplasm transport of RNA. In this mutant, not only the induction, but also a part of the repression in response to temperature upshift is largely inhibited. Conceivable mechanisms are discussed.

Fungal Proteins↗
PubMed1979

Comparison of rates of virus isolation from leukocyte populations separated from blood by conventional and Ficoll-Paque/Macrodex methods.

One hundred fifty-two blood specimens, largely from immunocompromised patients, were collected in heparinized Vacutainer tubes and divided into paired aliquots of equal volume. Buffy-coat preparations, containing mixed leukocyte and separate mononuclear and polymorphonuclear leukocyte populations were obtained by treatment of blood with conventional and Ficoll-Paque/Macrodex (F-P/M) methods. The development of cytopathic effect in monolayers of WI-38 fibroblasts inoculated with cell suspensions derived from the two methods was used to assess virus infectivity. Twice as many virus isolations were obtained using F-P/M. Of those viruses isolated by both conventional and F-P/M, the development of cytopathic effect was more extensive using the latter method. Moreover, a greater variety of viruses was isolated using F-P/M method, as compared to the conventional method. The F-P/M method is no more time consuming than conventional procedures, is readily adaptable for use in the diagnostic virology laboratory, requires only minimal additional cost, and is a particularly suitable and effective means of monitoring viremia.

Adenoviruses, Human↗
PubMed1979

Electrophoretic characterization of intracellular forms of bacteriophage phi X174 DNA: identification of novel intermediate of altered superhelix density.

The replication cycle of bacteriophage phi X174 DNA has been analyzed by agarose gel electrophoresis. The electrophoretic behavior of the predominant species of parental and progeny DNA molecules formed between 5 and40 min after infection was deduced and quantitated. Migration through 1.4% agarose at 5 and 10 V/cm resolved all known viral DNA species as well as fragments of host chromosomal DNA. Among parental replicative form(RF) molecules synthesized, 1 to 3% were full length linear duplexes (RFIII) and approximately 65% were closed circular duplexes (RFI). Most of the input viral strands remained in a duplex structure throughout the period of infection studied here. Among progeny molecules, RFIII was not readily detected unless viral DNA synthesis was inhibited by chloramphenicol. Late in infection, 20% of the progeny RF were found to exist as form I dna. in addition, approximately 1% of the viral DNA was found as unit length linear single strands. Electrophoretic analysis of RF DNA after controlled denaturation suggests the existence of four populations of closed circular RF: (i) molecules of native superhelix density (RFI); (ii) a population of molecules of altered topological linking number, alpha, differing in increments of one superhelical turn (tau) between tau values of 0 and approximately -31; (iii) a superimposed population of topological isomers which under electrophoresis conditions have mean tau value (tau) equal to +5; and (iv) a population of "complexed" molecules with a reduced number of superhelical turns due to their association with single-stranded DNA and RNA. Complexed parental molecules isolated from cells infected at high multiplicity released FRI and homologous single-stranded DNA upon denaturation and are postulated to be intermediates in genetic recombination. Complexed RF DNA isolated from cells infected at low multiplicity release native supercoils upon reaction with RNase H and are observed by electron microscopy to contain displacement loops. Such molecules are likely intermediates in transcription. Our results are consistent with a structure of complexed RFI involving a partially triple-stranded helix in which a covalently closed circular duplex molecule contains a reduced number of superhelical turns due to the unwinding produced by base pairing between one strand of the supercoil and an associated homologous single strand of DNA or RNA.

Bacteriophage phi X 174↗
PubMed1978

Plasma clearance of glycoproteins with terminal mannose and N-acetylglucosamine by liver non-parenchymal cells. Studies with beta-glucuronidase, N-acetyl-beta-D-glucosaminidase, ribonuclease B and agalacto-orosomucoid.

Glycoproteins having mannose and/or N-acetylglucosamine in the terminal non-reducing position [Stockert, Morell & Scheinberg (1976) Biochem. Biophys. Res. Commun. 68, 988--993], and various lysosomal enzymes [Stahl, Schlesinger, Rodman & Doebber (1976) Nature (London) 264, 86--8] are rapidly cleared from plasma by the liver after intravenous administration. A liver cell-separation technique was used to determine the cellular localization of 125I-labelled beta-glucuronidase, ribonuclease B, agalacto-orosomucoid and asialo-orosomucoid. On a specific readioactivity basis, all ligands except 125I-labelled asialo-orosomucoid were enriched in the non-parenchymal cell fraction. Isolated cells, fixed and stained for beta-glucuronidase or N-acetyl-beta-D-glucosaminidase activity after intravenous injection of the enzymes, showed enrichment in the non-parenchymal cell fraction (probably Kupffer cells). After uptake by the non-parenchymal cells, liver lysosomal beta-glucuronidase and N-acetyl-beta-D-glucosaminidase showed degradation half-times of 2.2 and 0.4 days respectively.

Acetylglucosamine↗