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Biomedical subjects

C A Ryan

Publications and source records attributed to C A Ryan.

At least 127 records · Page 7Linked to original sources
PubMed1994

Inhaled nitric oxide in infants referred for extracorporeal membrane oxygenation: dose response.

To determine the role of inhaled nitric oxide (NO) in a population of critically ill hypoxic near-term infants and to determine the dose response to inhaled NO, we examined a consecutive group of 23 infants referred for neonatal extracorporeal membrane oxygenation (ECMO) who had an oxygen index of 20 or greater after treatment with bovine surfactant. Inhaled NO was administered in concentrations from 5 to 80 ppm in random order to 23 infants. Overall, 13 infants had a significant response (an improvement in arterial oxygen pressure > 10 mm Hg or arterial oxygen saturation > 10%) to the first administration of inhaled NO, and one infant had a late response. There was no significant difference in the response to inhaled NO as measured by changes in arterial oxygen pressure or in the alveolar-arterial difference in partial pressure of oxygen, for any of the doses from 5 to 80 ppm. Thirteen infants had echocardiographic evidence of persisted pulmonary hypertension; 11 of these infants responded, compared with 3 responders among the 10 infants without persistent pulmonary hypertension of the newborn (p < 0.01). Overall, 11 infants required ECMO; there were two deaths in this group. Seven infants had congenital diaphragmatic hernia; five of those had a response to NO inhalation and four required ECMO. Our study demonstrates that there is no significant difference in response between low and high doses of inhaled NO and that this treatment may prevent the need for ECMO in some infants referred for this therapy, especially in infants with pulmonary hypertension. Prospective, controlled, randomized, and blinded trials of low doses of inhaled NO are needed to determine the clinical role of this potentially useful therapy.

Administration, Inhalation↗
PubMed1994

Increases in human epidermal DR+CD1+, DR+CD1-CD36+, and DR-CD3+ cells in allergic versus irritant patch test responses.

In an attempt to differentiate an allergic patch test response from an irritant response, we evaluated by flow cytometry the percentages of various epidermal cell populations isolated from allergen and irritant-treated patch test sites. Nine allergic individuals were patch tested with various allergens (Rhus, dinitrochlorobenzene [DNCB], or nickel chloride) and a vehicle control for 48 h. Eight additional individuals were patch tested with irritating chemicals (sodium lauryl sulfate or nonanoic acid) and with a vehicle control for 48 h. Epidermal cells, isolated from suction blisters, were double labeled for CD1/HLA-DR, CD3/HLA-DR, or CD36/HLA-DR cell surface markers and analyzed by flow cytometry to determine the percentage of various cell populations. A mean increase of 0.91 +/- 0.3 in the percentage of DR+CD1+ Langerhans cells over the vehicle control patch test site was detected in allergen-positive patch test sites in allergic individuals, whereas a decrease of 0.19 +/- 0.2 in the percentage of DR+CD1+ Langerhans cells from the vehicle control patch test site was detected in irritant-treated patch test sites. Epidermal cells from allergen-positive patch test sites also exhibited an increase of 5.2 +/- 1.8 in percentage of DR+CD1- cells over the vehicle control patch test site compared to an increase change of 0.8 +/- 0.4 in epidermal cells isolated from irritant-treated patch test sites. We also found that DR+ cells that lacked the CD1 determinant expressed the macrophage/monocyte antigen CD36 (OKM5). Finally, a 2.3 +/- 0.8 increase in the percentage of DR-CD3+ cells over the vehicle control patch test site was observed in allergen-positive patch test sites compared to an increase of 0.2 +/- 0.2 observed in irritant-treated patch test sites. These results demonstrate a significant increase in DR+CD1+, DR+CD1-CD36+, and DR-CD3+ epidermal cells in allergen-positive patch test sites compared to irritant patch test sites.

Adult↗
PubMed1994

Effects of magnesium sulphate and nitric oxide in pulmonary hypertension induced by hypoxia in newborn piglets.

AIM: To examine the haemodynamic effects of intravenous magnesium sulphate on an animal model of neonatal pulmonary hypertension induced by hypoxia. METHODS: The cardiac index (Q), pulmonary arterial pressure (PAP), systemic arterial pressure (SAP), and pulmonary (PVRI) and systemic (SVRI) vascular resistance indices were measured in nine newborn piglets (including three controls). Pulmonary hypertension was induced by lowering the FIO2 to 0.12-0.14, after which there was a significant increase in PAP and PVRI (37% and 142%, respectively; p < 0.01) and a significant fall in SAP and Q (30% and 33%, respectively; p < 0.01). RESULTS: Magnesium sulphate was infused intravenously as four doses of 25 mg/kg, 15 minutes apart, which resulted in a significant mean (SD) increase in serum magnesium (0.83 (0.07) mmol/l to 1.82 (0.19) mmol/l; p < 0.01). After the initial dose SAP, SVRI, PAP and PVRI decreased, but not significantly. Each subsequent dose of (50, 75, 100 mg/kg) was accompanied by further significant reductions in these variables from control baseline (p < 0.05). The PVRI:SVRI ratio remained unchanged throughout. Inhaled nitric oxide (NO) 40 ppm was administered after the last dose of magnesium sulphate. The PVRI:SVRI significantly decreased (p < 0.05), indicating that reversible pulmonary hypertension remained after a maximum dose of magnesium sulphate. CONCLUSIONS: Unlike NO, magnesium sulphate is not a selective pulmonary vasodilator and may lead to deleterious effects on systemic pressures in critically ill newborns.

Animals↗
PubMed1994

Polypeptide signalling for plant defence genes.

The synthesis of proteinase inhibitor proteins in response to wounding is a defensive response against pest and pathogen attacks. Wounding of leaves results in the release of a mobile wound signal which induces proteinase inhibitor synthesis throughout the plant. The signal transduction pathway regulating this response is not fully understood, but several compounds have been identified which are capable of inducing proteinase inhibitor synthesis in tomato and potato leaves. These compounds include cell wall fragments of both plant and pathogen origin [1-3], abscisic acid [4], jasmonic acid [5] and, most recently, an 18-amino-acid polypeptide, called systemin, isolated from tomato leaves [6]. In this chapter, we describe the properties of systemin and its precursor prosystemin, and we summarize the evidence supporting a role for systemin as an initial signal that regulates proteinase inhibitor synthesis in response to wounding.

Amino Acid Sequence↗
PubMed1994

Changing attitudes and practices regarding local analgesia for newborn circumcision.

STUDY OBJECTIVE: To change physician attitudes and practices regarding the routine use of local and regional anesthesia for newborn circumcision. DESIGN: Interventional study, followed by an audit of physician practice over a 1-month period, 1 year following interventions. SETTING: The newborn nurseries of the Women's Pavilion, Royal Alexandra Hospital, Edmonton. INTERVENTIONS: A broad range of awareness and educational programs were directed at physicians who perform newborn circumcisions, including posters, newsletters, presentations at grand rounds, video recordings, and practical "hands-on" demonstration of the techniques of local anesthesia to the prepuce and dorsal penile nerve block. RESULTS: Only one physician was using local analgesia for newborn circumcision prior to the introduction of the educational program. The audit, performed 12 months later, documented 46 circumcisions performed by 22 physicians, each performing between 1 and 6 circumcisions (median = 1). Sixteen of the 22 physicians (73%) used either local anesthesia to the prepuce (19 cases) or dorsal penile nerve block (13 cases) during circumcisions. Thus, local analgesia was used in 66% (32/48) of all circumcisions. Six physicians, performing 16 circumcisions, do not use any form of analgesia. CONCLUSIONS: This simple educational program has been associated with a remarkable change in attitudes and practice regarding local analgesia for neonatal circumcision. Our ideal objective, which we hope to achieve through repeated education and practical demonstrations of the techniques to interested physicians, is that all newborn circumcisions are performed under local or regional anesthesia in our institution.

Alberta↗
PubMed1993

Expression of an antisense prosystemin gene in tomato plants reduces resistance toward Manduca sexta larvae.

The growth rates of Manduca sexta (tobacco hornworm) larvae feeding on tomato plants constitutively expressing a prosystemin antisense gene were approximately 3 times higher than growth rates of larvae feeding on nontransformed control plants. The levels of proteinase inhibitor I and inhibitor II proteins in leaves of tomato plants expressing the antisense prosystemin gene remained at undetectable levels until the sixth day of larval feeding and then increased throughout the plants to 100-125 microg/g of leaf tissue after 14 days. In control plants, levels of proteinase inhibitor I and II proteins increased rapidly from the second day of larval feeding and by the eighth day contained levels of 225 microg/g of leaf tissue and 275 microg/g of leaf tissue, respectively, and then increased slowly thereafter. Prosystemin mRNA levels in antisense and control plants after 6 days and 12 days of larval feeding correlated with levels of inhibitor I and II protein levels. These experiments demonstrate that resistance of plants toward an insect pest can be modulated by genetically engineering a gene encoding a component of the inducible systemic signaling system regulating a plant defensive response.

Journal Article↗
PubMed1993

Drowning deaths in people with epilepsy.

OBJECTIVE: To determine the demographic characteristics and risk factors associated with death from drowning among people with epilepsy. DESIGN: Retrospective review of medical examiner's investigations into deaths from drowning from Jan. 1, 1981, to Dec. 31, 1990. SETTING: Alberta. MEASURES: Personal data, medical history, circumstances surrounding the death, autopsy findings and results of postmortem toxicologic analyses. RESULTS: Of 482 deaths from drowning in Alberta during the study period, 25 (5%) were considered by the medical examiner's office to be directly related to seizures. Fifteen (60%) of the 25 deaths occurred while the person was taking a bath, unsupervised. Only one person (4%) died while taking a shower. The remaining deaths occurred on a river or lake (16%), in a private pool (8%), in a public pool (8%) and in a jacuzzi (4%). Two people fell out of moving boats while having a seizure; neither had been wearing a personal flotation device. Nineteen (83%) of 23 people who had been receiving anticonvulsant drug therapy had undetectable or subtherapeutic levels of one or more of the drugs at autopsy. Ethanol was not a factor in any of the deaths. CONCLUSIONS: Seizure-related drownings represent a small but potentially preventable proportion of all drownings. Enhanced seizure control and compliance with anticonvulsant drug therapy may prevent some of these deaths. In addition, all people with epilepsy, regardless of the level of control of their condition, should be encouraged to take showers while sitting instead of baths. The presence of people in the same house who are not directly supervising the person in the bathroom does not protect against drowning. Personal flotation devices should be worn at all times during boating activities.

Accidents, Home↗
PubMed1993

Structure-activity of deleted and substituted systemin, an 18-amino acid polypeptide inducer of plant defensive genes.

The primary structure-activity relationships of systemin, an 18-amino acid polypeptide from tomato leaves that regulates the expression of two wound-inducible proteinase inhibitor genes in tomato and potato plants, were investigated. Analogs of systemin, the only example of a polypeptide signal from plants, were synthesized with progressive deletions of amino acids from both the NH2 terminus and COOH terminus and assayed in young excised tomato plants. All of the analogs exhibited severely decreased proteinase inhibitor-inducing activities, indicating that the entire 18-amino acid sequence is necessary for maximal activity. Deletion of the COOH-terminal Asp abolished inducing activity. Progressive replacement of each amino acid of the entire polypeptide with Ala revealed two regions, near residues Pro13, where Ala substitution reduced activity to less than 0.2%, and Thr17, which totally inactivated the analog. Other replacements with Ala had little or only moderate effects on activity. The two inactive analogs, des-Asp18 systemin and Ala17 systemin, were potent inhibitors of the inducing activity of the native systemin. These analogs, therefore, contain structural conformations sufficient for competition with systemin, but they are not competent for proteinase inhibitor gene induction. A synthetic COOH-terminal tetrapeptide, Met-Gln-Thr-Asp, retained low proteinase inhibitor inducing activity, but virtually any replacements with other amino acids either eliminated activity or reduced the activity to very low or nearly undetectable levels. These results indicate that residues near the COOH terminus of systemin are necessary for activity, possibly involving a phosphorylation at Thr17, and that other regions of the systemin sequence are important for interacting with a receptor(s) but are not sufficient to activate proteinase inhibitor gene expression.

Amino Acid Sequence↗
PubMed1993

DNase I and micrococcal nuclease analysis of the tomato proteinase inhibitor I gene in chromatin.

The chromatin structure of the wound-inducible proteinase inhibitor I gene was investigated in nuclei from leaves of wounded and unwounded tomato plants. DNase I digestion of intact nuclei revealed that the inhibitor I chromatin structure was highly sensitive to the enzyme compared to the inactive ribosomal chromatin. This sensitivity was independent of wounding. Digestion of tomato nuclei with micrococcal nuclease, which produces a nucleosomal ladder from bulk chromatin in agarose gels, supported these observations. Micrococcal nuclease produced only a faint nucleosomal repeat superimposed on a smear for the coding region of the inhibitor I gene, whereas digestion of inactive ribosomal chromatin produced a well defined nucleosomal ladder. Two DNase I-hypersensitive sites were found in the promoter region of the inhibitor I gene. Both were present before and after wound induction. These two constitutive DNase I-hypersensitive sites may correspond to DNA regulatory regions of the gene. The combined results indicate the existence of an open chromatin conformation in the inhibitor I gene DNA region, present before gene induction by wounding.

Cell Fractionation↗
PubMed1993

Isolation of signaling mutants of tomato (Lycopersicon esculentum).

As a first step towards developing a genetic system for investigating signaling processes in plants, we have developed a screen for signaling mutants deficient in a wound response. We have isolated two mutants of tomato that lack detectable production of proteinase inhibitors induced systemically in leaves by wounding. The mutants are deficient in the induction of both proteinase Inhibitor I and proteinase Inhibitor II but can be induced to respond at near wild-type levels by methyl jasmonate, a known elicitor of inhibitor production in tomato. While completely deficient in systemic production of proteinase inhibitors, both mutants produce some proteinase inhibitor in wounded leaves. This evidence suggests the existence of two signaling pathways, one local and one systemic, that regulate the induction of proteinase inhibitor synthesis in response to wounding.

Acetates↗
PubMed1993

Seizures due to lidocaine toxicity in a child during cardiac catheterization.

A 17-month-old boy developed grand mal seizures secondary to lidocaine toxicity during balloon dilatation of a congenital pulmonary valve stenosis. Lidocaine at 38 mg/kg (nine times the recommended maximum dose of 4.5 mg/kg) was administered during a 90-min period in order to optimize local anesthesia. This resulted in toxic serum lidocaine levels (8.7 mg/L; therapeutic range, 1.5-5 mg/L) at the time of seizures. Caution should be exercised with local anesthetics during invasive cardiac catheterizations. Hypercarbia (which lowers the seizure threshold to local anesthetics) should be avoided and the temptation to exceed the maximum recommended dose resisted.

Anesthesia, Local↗
PubMed1993

No resuscitation and withdrawal of therapy in a neonatal and a pediatric intensive care unit in Canada.

STUDY OBJECTIVE: To compare and contrast the modes of death in a neonatal (NICU) and a pediatric (PICU) intensive care unit. DESIGN: Retrospective analysis of patient records. SUBJECTS: All newborn infants and children (< 17 years of age) who died in the NICU and PICU at the University of Alberta Hospitals, Edmonton, between Jan. 1, 1990, to Dec. 31, 1991. RESULTS: The mortality rate in the PICU was 8.7% (73/839) compared with 5.6% (75/1333) in the NICU (p = 0.007). Withdrawal of therapy was the most common cause of death in both units and occurred more commonly in the NICU (NICU = 69% vs PICU = 34%; p = 0.01). There were significantly more deaths as a result of failed cardiopulmonary resuscitation (CPR) in the PICU than in the NICU (29% vs 13%; p = 0.046). Death after no-CPR orders occurred with equal frequency in both units (NICU 17%; PICU 15%). Brain death accounted for 22% (16/87) of PICU deaths; no infant in the NICU was declared brain dead (p < 0.05). When deaths resulting from brain death and failed CPR were excluded, there was no significant difference between the two units regarding withdrawal of therapy (NICU 80% vs PICU 69%) and no-CPR orders (NICU 20% vs PICU 30%). CONCLUSIONS: This study confirms that both withdrawal of therapy and no-CPR orders are part of current clinical practice in both the NICU and PICU settings. The ethical foundations and implications of these practices need further elaboration.

Alberta↗
PubMed1993

Purification and characterization from tobacco (Nicotiana tabacum) leaves of six small, wound-inducible, proteinase isoinhibitors of the potato inhibitor II family.

Six small molecular mass, wound-inducible trypsin and chymotrypsin inhibitor proteins from tobacco (Nicotiana tabacum) leaves were isolated to homogeneity. The isoinhibitors, cumulatively called tobacco trypsin inhibitor (TTI), have molecular masses of approximately 5500 to 5800 D, calculated from gel filtration analysis and amino acid content. The amino acid sequence of the entire 53 residues of one isoinhibitor, TTI-1, and the sequence of 36 amino acid residues from the N terminus of a second isoinhibitor, TTI-5, were determined. The two isoinhibitors differ only at residue 11, which is threonine in TTI-1 and lysine in TTI-5. The isoinhibitors are members of the potato inhibitor II family and show considerable identity with the small molecular mass members of this family, which include the eggplant inhibitor, two small molecular mass trypsin and chymotrypsin inhibitors from potatoes, and an inhibitor from pistils of the ornamental plant Nicotiana alata. Antibodies produced against the isoinhibitors in rabbits were used in radial immunoassays to quantify both the systemic wound inducibility of TTI in tobacco leaves and its constitutive levels in flowers.

Amino Acid Sequence↗
PubMed1993

Surgical and postoperative management of two neonates with necrotizing fasciitis.

Two neonates who presented with necrotizing fasciitis (NF) secondary to omphalitis were treated by radical excision of the anterior abdominal wall. Postoperatively, renal failure in both children was managed by continuous arteriovenous hemofiltration (CAVH). One child survived; the other died of sepsis. Serum lactate levels, which were 10 to 15 times the normal levels in both infants postoperatively, decreased rapidly in the survivor, but never approached normal levels in the infant who died. Although the best prospect for survival in neonatal NF remains prompt, radical, surgical excision and is associated with a low threshold for repeat débridement, modern supportive measures (including CAVH) may enhance survival.

Acute Kidney Injury↗
PubMed1992

Ribosomal gene clusters are uniquely proportioned between open and closed chromatin structures in both tomato leaf cells and exponentially growing suspension cultures.

The accessibility of regulatory molecules to specific DNA sequences and chromatin regions in the nucleus is crucial to gene expression. In this study, we examined the chromatin structure in tomato leaf cells and in exponentially growing tomato cell suspension cultures. The structure of ribosomal chromatin was investigated by micrococcal nuclease and psoralen photocrosslinking. We showed that ribosomal genes in tomato are folded into two distinct types of chromatin: an open chromatin conformation and a closed nucleosomecontaining chromatin. In contrast to previous findings in Friend cells, where half of the ribosomal genes were found to be complexed within an inactive chromatin structure, we demonstrated that the canonical nucleosome-containing chromatin is present in the majority (approximately 80%) of the tomato rRNA-encoding DNA clusters. The minor open chromatin population (approximately 20% of the ribosomal genes) could be detected only after analysis following psoralen crosslinking. The relative amounts of the two ribosomal chromatin structures are similar in stationary and exponentially growing cells. This suggests that the proportions of open and closed chromatin structures present in either stationary or exponentially growing tomato cells are not dependent on the transcriptional process.

Journal Article↗
PubMed1992

Oligouronide signaling of proteinase inhibitor genes in plants: structure-activity relationships of Di- and trigalacturonic acids and their derivatives.

Polygalacturonic acid (DPave approximately 20), alpha-1,4-di- and trigalacturonic acids, delta 4,5-alpha-1,4-di- and delta 4,5-alpha-trigalacturonic acids, and several chemically modified derivatives of these oligomers were prepared. Their proteinase inhibitor-inducing activities were determined by supplying solutions of the compounds to young, excised tomato plants through their cut stems. Digalacturonic acid, on a molar basis, was the most active oligomer (ED50 approximately 1.5 micrograms/plant), being about three times more active than the parent oligogalacturonic acid (ED50 approximately 5.5 micrograms/plant). The specific inducing activity of trigalacturonic acid was about half that of digalacturonic acid. Both delta 4,5-di- and delta 4,5-trigalacturonic acids were about half as active as di- and trigalacturonic acids, respectively. Reduction of the hemiacetal (carbonyl) group of the di- and trigalacturonic acids with sodium borohydride completely destroyed proteinase inhibitor inducing activities, indicating that the inducing activity of both acids depends upon an intact hemiacetal at the reducing termini. Reduction of the double bonds of delta 4,5-di- and delta 4,5-trigalacturonic acids by catalytic hydrogenation with H2 (palladium catalyst) produced derivatives with specific inducing activities of approximately one-half that of the parent compounds. Thus, while the reducing termini of oligogalacturonides require an intact hemiacetal for proteinase inhibitor inducing activities, the nonreducing termini of the small oligouronides do not require a C4 hydroxyl nor a C5 proton to be active inducers.

Carbohydrate Conformation↗
PubMed1992

Structure, expression, and antisense inhibition of the systemin precursor gene.

A gene that encodes systemin, a mobile 18-amino acid polypeptide inducer of proteinase inhibitor synthesis in tomato and potato leaves, has been isolated from tomato, Lycopersicon esculentum. Induction of proteinase inhibitors in plants is a response to insect or pathogen attacks. The gene has 10 introns and 11 exons, ten of which are organized as five homologous pairs with an unrelated sequence in the eleventh, encoding systemin. Systemin is proteolytically processed from a 200-amino acid precursor protein, prosystemin. Prosystemin messenger RNA was found in all organs of the plant except the roots and was systemically wound-inducible in leaves. Tomato plants transformed with an antisense prosystemin complementary DNA exhibited greatly suppressed systemic wound induction of proteinase Inhibitor I and II synthesis in leaves.

Amino Acid Sequence↗