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Biomedical subjects

M Leonard

Publications and source records attributed to M Leonard.

At least 55 records · Page 3Linked to original sources
PubMed1998

Interleukin-1 increases expression of the LYT-10 (NFkappaB2) proto-oncogene/transcription factor in renal cell carcinoma lines.

The LYT-10 gene was initially cloned by virtue of its disruption by the translocation breakpoint in some t(10;14) lymphoid neoplasms. LYT-10 is now known to encode a component of the NF-kappaB family of transcriptional activators and has therefore also been designated NFkappaB2. Activation of NF-kappaB is generally associated with its transfer to the nucleus and is followed by a rapid increase in expression of its target genes, which include cytokines such as interleukin-6 (IL-6). IL-6 can also be induced by other transcription factors such as NF-IL6. We studied the interaction of IL-1 and these transcription factors in two renal cell carcinoma cell lines (ACHN and Caki-1). These lines produce high levels of IL-6, show endogenous chloramphenicol acetyltransferase activity for the IL-6 promoter, and have high basal levels of transcripts encoding the NF-kappaB components Lyt-10, p50, and p65 as well as the NF-IL6 transcription factor. IL-1alpha and IL-1beta markedly increased steady-state levels of LYT-10 (NFkappaB2) transcripts and nuclear Lyt-10 protein in both cell lines. Levels of the NFkappaB1 (p50-encoding), p65, and NF-IL6 transcripts also increased after IL-1 exposure. These changes were accompanied by a 20-fold or greater increase in levels of IL-6 messenger ribonucleic acid (mRNA) and protein. Our observations suggest that the mechanism by which IL-1alpha or IL-1beta induces IL-6 may be mediated through increases in LYT-10 mRNA and protein levels as well as increases in expression of other transcription factors (NFkappaB1, p65, and NF-IL6), in addition to the known ability of IL-1 to post-translationally activate NF-kappaB.

Blotting, Northern↗
PubMed1998

Breakdowns on the path of chronic illness: opportunities for learning.

An unusual case of calciphylaxis, presenting at the onset of end-stage renal disease and evolving into an extended and arduous hospital stay, is described. The medical approach to this case is addressed briefly, but the main focus of this paper is to describe, in the words of various participants, the events and interactions that occurred and to learn from this description how our management of such cases breaks down. When confronted by difficult circumstances, it is common for us to react emotionally in ways that are automatic and based on our own personal histories and behavior patterns. Such automatic reactions prevent us from seeing and understanding what we really need to know about a given situation and leave us vulnerable to discouragement and internal suffering when clinical events do not go well (A. Nierenberg, personal communication, April 1998). The result is often exasperation with patients and families, as well as emotionally laden interactions that do not forward problem solving. In retrospect, the appearance of such breakdowns is not only predictable in the course of chronic illness, but offers us the opportunity to observe our automatic reactions, to re-evaluate our approach, and to redesign our actions. We have written this review, not to find error or blame, but rather to emphasize that we are learning to view these breakdowns as signals first to step back from our automatic reactions and then to listen and communicate clearly as a means to navigating the best pathway through difficult and discouraging clinical challenges.

Calciphylaxis↗
PubMed1998

The manufacturing process for recombinant factor IX.

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.

Animals↗
PubMed1997

New packing materials for protein chromatography.

This review describes new packing materials designed for protein chromatography, covering advances in base supports and stationary phases. Base supports are classified according to their chemical composition. Since most separation media are bead shaped, typical procedures used for their preparation are also presented. In order to provide matrices combining improved chemical stability and chromatographic performances, composite materials continue to be developed, including bonded stationary phases, pore composites and mixed carriers. The different approaches to their preparation are described and characteristics that play a major role in the chromatographic process are discussed. Recently introduced materials and some of their applications under non-denaturing conditions in the different chromatographic modes are also presented.

Chromatography, Liquid↗
PubMed1997

Chemical cardiac sympathetic denervation hampers defibrillation in the dog.

INTRODUCTION: Cardiac defibrillation is influenced by several physical and nonphysical factors. Previous animal studies have shown that beta-adrenergic stimulation facilitates the process of defibrillation. The purpose of this study was to examine the effects of chemical sympathetic denervation on the ability to defibrillate the canine heart. METHODS AND RESULTS: Twelve chronically instrumented dogs underwent serial measurements of the energy required to defibrillate the heart, ten before and after treatment with 50 mg/kg 6-hydroxydopamine (6-OHDA). Two of the animals received 1% ascorbic acid in 0.9% saline solution (the vehicle) only, and three dogs received the vehicle followed several weeks later by 6-OHDA. Following treatment with 6-OHDA, the energy to defibrillate the heart rose from 11.9 +/- 7.4 J (baseline 1) and 14.3 +/- 8.7 J (baseline 2) to 23.3 +/- 10.8 J (P < 0.01 and < 0.05, respectively). In contrast, following saline administration, no significant change was measured in the energy required to defibrillate the heart. After 6-OHDA, 5 of the 10 animals could not be defibrillated versus none of 5 after saline treatment (Chi square 3.750, P = 0.053). In surviving animals, a return of measurements to, or toward, baseline was measured after active treatment. CONCLUSIONS: In this chronically instrumented, closed chest animal model, chemical sympathetic denervation with 6-OHDA hampered the process of cardiac defibrillation. These results support previous observations of a modulating effect of this process by adrenergic activity.

Animals↗
PubMed1997

Pulmonary serotonin 5-HT3-sensitive afferent fibers modulate renal sympathetic nerve activity in rats.

Cardiopulmonary reflexes with vagal afferents may control volume homeostasis by influencing renal nerve activity. Such reflexes can be stimulated mechanically and chemically, e.g., by serotonin 5-HT). We have demonstrated that stimulation of epicardial 5-HT3 receptors inhibits renal sympathetic nerve activity (RSNA) by a cardiorenal reflex. We now tested the hypothesis that pulmonary 5-HT3-sensitive vagal afferent fibers participate in the control of renal nerve activity. Two sets of experiments were performed. First, the responses of multifiber RSNA, heart rate (HR), and blood pressure (BP) to the 5-HT3-receptor agonist phenylbiguanide (PBG; 10 microg iv) were recorded in the presence of intact pulmonary afferents. Abdominal afferents were removed by subdiaphragmatic vagotomy. Cardiac afferents were blocked by intrapericardial injection of 10% procaine. Second, the responses of 25 single vagal pulmonary afferent C fibers to PBG were assessed. PBG decreased BP, HR, and RSNA (-90 +/- 8%). When cardiac afferents were blocked by procaine, BP and HR failed to decrease in response to PBG; however, the RSNA decrease was still -48 +/- 8%. Single fibers generally responded to PBG by a slight increase in firing rate. A distinct subset of fibers (5 of 25) showed an activity increase of >15 Hz that preceded changes in BP and HR. The decreased RSNA in the absence of cardiac and abdominal vagal afferents and the strong response of 20% of pulmonary single fibers to intravenous PBG suggest that pulmonary fibers play a role in a 5-HT3 serotenergic reflex. Thus pulmonary serotonin could influence the neural control of renal function.

Afferent Pathways↗
PubMed1997

The use of a Hemocue blood glucose analyser in a neonatal unit.

Near patient testing for glucose is now a widely accepted procedure in hospital wards and clinics. However, in a neonatal ward where the detection of hypoglycaemia rather than hyperglycaemia is of paramount importance, it is more difficult to find a suitable glucose monitoring instrument. We compared two Hemocue blood glucose analysers (Hemocue Ltd) in our special care baby unit (SCBU) with the laboratory procedures and found that the Hemocue may overestimate the glucose by as much as 2.5 mmol/L. In addition, Hemocue analysers are costly to run. We feel these analysers may be more useful in a general ward rather than in a SCBU.

Blood Glucose↗
PubMed1997

Recovery times from subarachnoid blocks using bupivacaine hydrochloride and tetracaine hydrochloride with and without epinephrine.

This retrospective study examined the length of time patients spent in the postanesthesia care unit (PACU) recovering from a subarachnoid block with either bupivacaine hydrochloride or tetracaine hydrochloride with and without epinephrine after total knee replacement surgery or total hip replacement surgery. One hundred subjects' charts were reviewed with 50 subjects receiving a subarachnoid block with bupivacaine (25 had epinephrine added to the bupivacaine) and 50 subjects receiving a subarachnoid block with tetracaine (25 had epinephrine added to the tetracaine). There were no statistical differences among the groups with respect to age, height, weight, dose of local anesthetic, and length of surgical procedure. Patient who received tetracaine stayed longer in the PACU (64.44 minutes) and took longer to bend their knees (73.17 minutes), flex their hips (99.65 minutes), and have return of sensation (68.88 minutes), compared to those who had received bupivacaine (P < .05). When epinephrine was added to the local anesthetic, it prolonged the time until the return of knee flexion, hip flexion, and sensation by 66.82, 87.65, and 76.77 minutes respectively (P < .05).

Anesthetics, Local↗
PubMed1997

Monitoring pressure ulcers in nursing homes.

Clinical indicators may be used to monitor the quality of care delivery. Unfortunately, they are often viewed by nursing staff as unnecessary paper work. This study used Waterlow's Pressure Sore Risk Assessment Tool as the basis of a clinical indicator to monitor pressure ulcers within a nursing home. It was found that by closely monitoring the skin status of residents, preventative actions could be implemented, thereby minimizing the risk of pressure ulcer development. The advantage of utilizing such a tool is that it is seen to be clinically relevant for nursing staff while providing a bank of data for quality management.

Adult↗