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Biomedical subjects

L D Martin

Publications and source records attributed to L D Martin.

At least 55 records · Page 3Linked to original sources
PubMed1995

Visualization of nucleosomal substructure in native chromatin by atomic force microscopy.

Intact rDNA minichromosomes from Tetrahymena thermophila were isolated as native chromatin and imaged by atomic force microscopy (AFM). AFM measurements of condensed rDNA chromatin were consistent with a 30 nm fiber that frequently (87% of molecules observed) contained stretches of nucleosome cores arranged in a zig-zag conformation. Examination of rDNA chromatin in a dispersed conformation by tapping mode AFM in low humidity resulted in high resolution images of partially dissociated nucleosome cores and associated linker DNA. A majority of these nucleosome cores contained six to eight smaller particles with dimensions consistent with those of individual histones. Many of the nucleosome cores showed a striking resemblance to the wedge (35%), axial (15%), and front (6%) views of the nucleosome histone octamer modeled by Arents et al. [Arents, G., Burlingame, R. W., Wang, B.-C., Love, W.E., & Moudrianakis, E. N. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 10148-10152]. This direct visualization of histone subunits and nucleosomal substructure in native chromatin illustrates the potential use of AFM to localize individual proteins in condensed cellular chromatin.

Animals↗
PubMed1995

Mimosine differentially inhibits DNA replication and cell cycle progression in somatic cells compared to embryonic cells of Xenopus laevis.

The plant amino acid mimosine has been reported to block cell cycle progression and DNA replication in cultured mammalian cells, perhaps by blocking initiation. In this study, we show that mimosine does not block initiation or any other step in DNA replication in embryonic cells of Xenopus laevis. Mimosine does not block DNA replication in cell-free "cycling" extracts of Xenopus eggs, nor does it block M to S phase transition in cell-free egg extracts released from metaphase arrest. Microinjection of mimosine into 4-cell embryos had no visible effect on development during the first 3 days after fertilization. Prior to the midblastula transition, when the cell cycle consists of alternating S and M phases, neither chromosomal DNA replication nor replication of microinjected plasmid DNA were inhibited by mimosine microinjected into cleaving Xenopus embryos. Microinjection of mimosine after the midblastula transition, when large endogenous stockpiles of DNA replication components have begun to be depleted and Xenopus embryonic cells have acquired G1 and G2 phases, still did not inhibit cell cycle progression or DNA replication. In marked contrast, mimosine arrested the growth of proliferating cultured Xenopus kidney epithelial A6 cells near the G1/S boundary. We conclude that mimosine appears to block DNA replication and cell cycle progression in somatic cells, but has no apparent effect in rapidly dividing Xenopus embryonic cells.

Animals↗
PubMed1995

New approaches to ventilation in infants and children.

Recent insights into the pathophysiology of acute lung injury have led to changes in our routine approach to mechanical ventilation in this population of patients. Heterogeneous alterations in the anatomy and function of the lung are characteristic of acute lung injury. Experimental evidence strongly suggests that traditional approaches to mechanical ventilation with normal tidal volumes applied uniformly to the injured lungs will result in repetitive alveolar overdistention in regions with normal compliance. This process, termed volutrauma, impedes lung healing and may extend damage to previously unaffected areas. This realization has led to a strategy that is designed to avoid tidal alveolar collapse using physiologic transalveolar pressures while allowing alveolar hypoventilation and hypercapnia. Debate continues regarding the risks and benefits of pressure-limited versus volume-limited mechanical ventilation to achieve this goal. Research is ongoing regarding the role and techniques for nonconventional methods of cardiorespiratory support for this severely ill group of patients.

Acute Disease↗
PubMed1994

(E)-3-[[[[6-(2-carboxyethenyl)-5-[[8-(4- methoxyphenyl)octyl]oxy]-2-pyridinyl]-methyl]thio]methyl]benzoic acid and related compounds: high affinity leukotriene B4 receptor antagonists.

(E)-3-[[[[6-(2-Carboxyethenyl)-5-[[8-(4- methoxyphenyl)octyl]oxy]-2-pyridinyl]methyl]thio]methyl]benzoic acid (11, SB 201993) is a novel, potent LTB4 receptor antagonist. Compound 11 arose from a structure-activity study of a series of trisubstituted pyridines that demonstrated LTB4 receptor antagonist activity. The placement of an additional methylene unit in the sulfur containing chain linking the pyridine and benzoic acid moieties of lead compound 8 (K(i) = 80 nM) resulted in a greater than 10-fold increase in receptor affinity. Additionally, in this new series of compounds, the oxidation state of the sulfur was found to be critical to the activity, i.e., the sulfoxide and sulfone showed substantially lower affinity for the LTB4 receptor. Compound 11 competitively inhibits the binding of [3H]LTB4 to LTB4 receptors on human polymorphonuclear leukocytes with a Ki of 7.1 nM and blocks both the LTB4-induced calcium mobilization and the LTB4-induced degranulation responses in these cells with IC50 values of 131 and 271 nM, respectively. Compound 11 demonstrated oral LTB4 antagonist activity as well as topical antiinflammatory activity in the mouse.

Benzoates↗
PubMed1994

DNA sequence requirements for the regulation of immobilization antigen A expression in Paramecium tetraurelia.

The Paramecium surface proteins (immobilization antigens) are expressed in a mutually exclusive manner; only one antigen is found on the cell surface at a time. Expression of these proteins is regulated in response to environmental cues such as temperature and pH. This regulation has been shown to be controlled at the level of mRNA abundance by transcriptional and post-transcriptional mechanisms. Here, we have studied the transcription and regulated expression of the immobilization antigen A gene in Paramecium tetraurelia by transforming an A-deficient strain, d12, with cloned portions of the A gene via microinjection. The A gene is approximately 8 kilobases (kb) long with the transcription start site at position -9 or -8 and the start of translation at position +1. Paramecia transformed with cloned DNA containing A-gene sequences beginning at position -264 and ending 63 base pairs (bp) past the gene's polyadenylation site show properly regulated expression of immobilization antigen A. Lines derived from paramecia transformed with a plasmid containing A-gene sequences starting at position -211, however, show markedly reduced A-gene mRNA levels, and rarely express the A antigen. Nevertheless, cells that do express the A protein exhibit mutual exclusion and normal responses to environmental stimuli. Thus, the 54 bp between -264 and -211, while important for transcription, are not involved in the control of mutual exclusion and responses to environmental changes. Further deletion to position -151 yields similar, but more extreme, results.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Anesthetic implications of an upper respiratory infection in children.

Pediatricians and pediatric anesthesiologists are frequently confronted with the dilemma of a child scheduled for elective surgery with or recently recovered from an upper respiratory tract infection. Modifications of routine anesthetic practice may decrease but not eliminate risks of associated complications. Guidelines for the evaluation and triage of these children are presented.

Anesthesia↗
PubMed1994

Selective anesthetic inhibition of brain nitric oxide synthase.

BACKGROUND: It has been postulated that nitric oxide (NO) is a neurotransmitter involved in consciousness, analgesia, and anesthesia. Halothane has been shown to attenuate NO-mediated cyclic guanosine monophosphate accumulation in neurons, and a variety of anesthetic agents attenuate endothelium-mediated vasodilation, suggesting an interaction of anesthetic agents and the NO-cyclic guanosine monophosphate pathway. However, the exact site of anesthetic inhibitory action in this multistep pathway is unclear. The current study examines effects of volatile and intravenous anesthetic agents on the enzyme nitric oxide synthase (NOS) in brain. METHODS: NOS activity was determined by in vitro conversion of [14C]arginine to [14C]citrulline. Wistar rats were decapitated and cerebellum quickly harvested and homogenized. Brain extracts were then examined for NOS activity in the absence and presence of the volatile anesthetics halothane and isoflurane, and the intravenous agents fentanyl, midazolam, ketamine, and pentobarbital. Dose-response curves of NOS activity versus anesthetic concentration were constructed. Effects of anesthetics on NOS activity were evaluated by analysis of variance. RESULTS: Control activities were 57.5 +/- 4.5 pmol.mg protein-1.min-1 in the volatile anesthetic experiments and 51.5 +/- 6.5 pmol.mg protein-1.min-1 in the intravenous anesthetic experiments. NOS activity was not affected by ketamine (< or = 1 x 10(-4) M), pentobarbital (< or = 5 x 10(-5) M), fentanyl (< or = 1 x 10(-5) M), and midazolam (< or = 1 x 10(-5) M). Halothane decreased NOS activity to 36.7 +/- 2.5 (64% of control, P < 0.01 from control), 23.8 +/- 4.3 (41%, P < 0.01 from control and < 0.05 from 0.5% halothane), 25.2 +/- 3.8 (44%, P < 0.01 from control and < 0.05 from 0.5% halothane), and 19.7 +/- 2.8 (34%, P < 0.01 from control and < 0.05 from 0.5% halothane) pmol.mg protein-1.min-1 at 0.5, 1.0, 2.0, and 3.0% vapor. Isoflurane decreased NOS activity to 48.9 +/- 6.1 (85% of control), 46.0 +/- 3.2 (80%, P < 0.05 from control), 40.3 +/- 5.1 (70%, P < 0.05 from control), and 34.2 +/- 4.0 (60%, P < 0.05 from control and 0.5% and 1.0% isoflurane) pmol.mg protein-1.min-1 at 0.5, 1.0, 1.5, 2.0% vapor, respectively. CONCLUSIONS: Volatile anesthetics inhibit brain NOS activity in an in vitro system, but the intravenous agents examined have no effect at clinically relevant concentrations. This inhibition suggests a protein-anesthetic interaction between halothane, isoflurane, and NOS. In contrast, intravenous agents appear to have no direct effect on NOS activity. Whether intravenous agents alter signal transduction or regulatory pathways that activate NOS is unknown.

Amino Acid Oxidoreductases↗
PubMed1994

Optimal release time during airway pressure release ventilation in neonatal sheep.

OBJECTIVE: To systematically investigate the effect of altering release time during airway pressure release ventilation in a neonatal animal model before and after oleic acid-induced acute lung injury. DESIGN: Prospective, nonrandomized, controlled study with repeated measures. SETTING: University research laboratory. SUBJECTS: Eight neonatal sheep (aged < 7 days, weight 5.1 +/- 0.3 kg). INTERVENTIONS: Throughout this study, airway pressure release ventilation was performed with an FIO2 of 0.21 at a frequency of 0.5 Hz (30 breaths/min) and an airway plateau pressure set to deliver tidal volumes between 10 and 15 mL/kg with a release time of 1 sec. Release time was changed in decrements of 0.2 sec starting at 1 sec and ending at 0.2 sec at 10-min intervals. Cardio-respiratory profiles were recorded at the end of each interval. The total exhaled respiratory system time constant (tau) was measured by plotting exhaled volume (integration of exhaled air flow) vs. time. Acute lung injury was induced by oleic acid infusion. The protocol was repeated with increased plateau airway pressure to maintain tidal volumes between 10 and 15 mL/kg at a release time of 1 sec. MEASUREMENTS AND MAIN RESULTS: During airway pressure release ventilation at a release time of 1 sec, oleic acid-induced acute lung injury decreased dynamic lung compliance (9.9 +/- 2.2 vs. 7.5 +/- 2.0 mL/cm H2O, p < .01), the expiratory time constant (0.15 +/- 0.04 vs. 0.12 +/- 0.02 sec, p < .05), and mean arterial pressure (80 +/- 5 vs. 62 +/- 12 mm Hg, p < .01). Alveolar ventilation was maintained as long as release times were > 0.4 sec (approximately 3 tau or greater). PaO2 decreased with release times of < 0.3 sec, but the alveolar-arterial oxygen tension difference was unchanged. In this protocol, with higher plateau and mean airway pressures, oleic acid-induced acute lung injury had no effect on the relationship between release time and oxygenation or ventilation. CONCLUSIONS: In this neonatal laboratory model, release times that were much shorter than previously reported maintained clinically acceptable oxygenation and ventilation. The optimal duration of the release time is a function of the time constant of the respiratory system. During airway pressure release ventilation, alveolar ventilation was maintained without apparent lung volume loss with release times of between 4 tau and 10 tau.

Animals↗
PubMed1993

Right and left ventricular cultured endocardial endothelium produces prostacyclin and PGE2.

The endothelium profoundly affects subjacent vascular smooth muscle function. An analogous relationship between endothelial endocardial cells (EEC) and the myocardium is suggested by Brutsaert et al.'s observation that EEC modulate the contractility of subjacent myocardium. Prostanoids are a major product by which vascular endothelium affects smooth muscle, but similar prostanoid production by EEC has not been described. To determine whether both right and left ventricular EEC produce prostacyclin (PGI2) and prostaglandin E2 (PGE2), ovine EEC were cultured. EEC prostanoid production was measured under basal conditions and after stimulation with arachidonic acid or calcium ionophore A23187. EEC from both ventricles demonstrated sustained prostacyclin and PGE2 production. Prostacyclin production was 10 times greater than PGE2. These results suggest that endocardial prostanoid production could act both locally, to modulate platelet and myocardial function, and distally, on downstream vascular tone.

Animals↗
PubMed1993

Postoperative analgesia following thoracotomy in children: interpleural catheters.

The authors retrospectively review their experience in children with the latest addition to the postoperative analgesic armamentarium: interpleural analgesia (IPA). IPA was used in 14 children following thoracotomy. There were 9 boys and 5 girls. Patients varied in age from 2 months to 17 years 4 months (mean +/- SEM = 7.6 +/- 1.6 yr). Catheters were left in place from 10 to 72 hours (mean +/- SEM = 45.1 +/- 4.6 h). Four patients received intermittent bolus doses and 10 patients received a continuous infusion through the interpleural catheters. Adequate analgesia, as judged by both subjective responses (decreased irritability or complaints of pain) and by objective physiologic responses (decreased heart rate, respiratory rate, and systolic blood pressure), was achieved in 13 of 14 patients. Eight of the 14 children required no additional analgesic agents. One child received 2 doses of oral codeine and 4 patients received 2 to 3 doses of intravenous narcotic during IPA. IPA was not effective in one patient who required 6 doses of intravenous meperidine. Patients more than 10 years of age required significantly more (P < 0.05) intravenous narcotic supplementation than patients less than 10 years of age (1.60 +/- 0.50 v 0.14 +/- 0.11 mg meperidine/kg/d). No complications related to placement or subsequent use of IPA were identified in any of the patients. IPA provides effective postoperative analgesia following thoracotomy in children.

Adolescent↗
PubMed1993

Paracrine effects of endocardial endothelial cells on myocyte contraction mediated via endothelin.

Endocardial endothelium is reported to modulate myocardial contraction by releasing diffusible factors, but the nature of the agent(s) responsible is unknown. In the present study we investigated the potential role of endothelin in these effects. Cultured sheep endocardial endothelial cells were found to express endothelin-1 mRNA and to release endothelin-1 into superfusing solution. This superfusate induced positive inotropic effects in isolated rat cardiac myocytes, associated with an increase in the cytosolic Ca2+ transient. Similar positive inotropic effects were induced by vascular endothelial cell superfusate as well as by synthesized endothelin-1, administered at concentrations similar to those present in the superfusate. Incubation of endocardial endothelial cell superfusate with endothelin-1-specific antiserum reduced the free endothelin-1 concentration to undetectable levels and abolished both the positive inotropic effect and the rise in cytosolic Ca2+. These findings indicate that endocardial endothelial cells may modulate myocardial contraction in part through the release of endothelin-1 and suggest that endocardial as well as vascular endothelium could exert potent paracrine effects on myocardium.

Animals↗
PubMed1992

Acute hypoxia alters eicosanoid production of perfused pulmonary artery endothelial cells in culture.

Hypoxia alters vascular tone which regulates regional blood flow in the pulmonary circulation. Endothelial derived eicosanoids alter vascular tone and blood flow and have been implicated as modulators of hypoxic pulmonary vasoconstriction. Eicosanoid production was measured in cultured bovine pulmonary endothelial cells during constant flow and pressure perfusion at two oxygen tensions (hypoxia: 4% O2, 5% CO2, 91% N2; normoxia: 21% O2, 5% CO2, 74% N2). Endothelial cells were grown to confluence on microcarrier beads. Cell cartridges (N = 8) containing 2 ml of microcarrier beads (congruent to 5 x 10(6) cells) were constantly perfused (3 ml/min) with Krebs' solutions (pH 7.4, T 37 degrees C) equilibrated with each gas mixture. After a ten minute equilibration period, lipids were extracted (C18 Sep Pak) from twenty minute aliquots of perfusate over three hours (nine aliquots per cartridge). Eicosanoids (6-keto PGF1 alpha; TXB2; and total leukotriene [LT - LTC4, LTD4, LTE4, LTF4]) were assayed by radioimmunoassay. Eicosanoid production did not vary over time. 6-keto PGF1 alpha production was increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng/min/gm protein; p less than 0.01). Thromboxane production (normoxia 19 +/- 2 vs hypoxia 20 +/- 2 ng/min/gm protein) and total leukotriene production (normoxia 363 +/- 35 vs hypoxia 329 +/- 29 ng/min/gm protein) did not change with hypoxia. These data demonstrated that oxygen increased endothelial prostacyclin production but did not effect thromboxane or leukotriene production.

Animals↗
PubMed1992

Implementing the Public Health Social Work Forward Plan: a research-based prevention curriculum for schools of social work.

In 1985, the Division of Maternal and Child Health of the U.S. Public Health Service funded a major working conference entitled "Public Health Social Work in Maternal and Child Health: A Forward Plan." Curriculum recommendations for schools of social work were made, including a recommendation for the integration of health and mental health content in the education of social workers within a public health conceptual framework. In 1986, the National Institute of Mental Health funded a three-year program to develop and evaluate a research-based prevention training curriculum for dissemination to schools of social work and other primary care professional schools. This article examines the Michigan Prevention Training and Curriculum Development Project from the perspective of the recommendations of the Public Health Social Work Forward Plan.

Curriculum↗
PubMed1992

Halothane enhances pulmonary artery endothelial eicosanoid release.

To determine whether anesthetics alter endothelial eicosanoid release, cultured bovine pulmonary artery endothelial cells were studied during constant flow and pressure perfusion at two oxygen tensions (hypoxia, 50 +/- 2 mm Hg; normoxia, 144 +/- 5 mm Hg; mean +/- SEM) with and without 1% halothane. Endothelialized microcarriers containing approximately 5 x 10(6) cells were loaded into cartridges and perfused (3 mL/min) with Krebs' solution (pH 7.4, at 37 degrees C) equilibrated with each gas mixture. Eicosanoids (6-keto prostaglandin F1 alpha, thromboxane B2, and total peptidoleukotrienes [C4, D4, E4, F4]) were measured by radioimmunoassay and quantified per gram of cellular protein per minute. Eicosanoid release did not vary over time. The 6-keto prostaglandin F1 alpha release increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng.min-1 x g protein-1; P < 0.01). Halothane (H) increased release of each eicosanoid during both normoxia and hypoxia: 6-keto prostaglandin F1 alpha-normoxia 291 +/- 27 versus normoxia + H 356 +/- 32 ng.min-1 x g protein-1, hypoxia 395 +/- 35 versus hypoxia + H 464 +/- 40 ng.min-1 x g protein-1, P < 0.05; thromboxane B2-normoxia 19 +/- 2 versus normoxia + H26 +/- 2 ng.min-1 x g protein-1, hypoxia 20 +/- 2 versus hypoxia + H 38 +/- 5 ng.min-1 x g protein-1, P < 0.001; leukotriene-normoxia 363 +/- 35 versus normoxia + H 489 +/- 52 ng.min-1 x g protein-1, hypoxia 329 +/- 29 versus hypoxia + H 455 +/- 39 ng.min-1 x g protein-1, P = 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗