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Biomedical subjects

D J Murphy

Publications and source records attributed to D J Murphy.

At least 19 recordsLinked to original sources
PubMed1992

Secondary structures of a new class of lipid body proteins from oilseeds.

The three main isoforms of the 19-kDa lipid body proteins (oleosin) have been purified to homogeneity from embryos of rapeseed. The secondary structures of these proteins as derived from circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopy were compared with the secondary structures predicted from the primary sequences. The salient feature of the primary sequence of all oleosins is its division into three defined structural domains: a central hydrophobic domain flanked on either side by relatively hydrophilic domains, respectively. Using a variety of predictive methods based on primary amino acid sequence data, the oleosins exhibited a high probability of beta-strand structure in the 70-residue central hydrophobic domain, with relatively little alpha-helical content. Secondary structure data derived from CD and FTIR were consistent with the predictions from primary sequence, showing that the oleosins contained about 45% beta-strand and 13% alpha-helical structure. Under high salt conditions, a 40-kDa polypeptide was obtained from purified preparations of the 19-kDa oleosins. The 40-kDa polypeptide has a very similar secondary structure, as analyzed by CD and FTIR, to that of the 19-kDa oleosins. This polypeptide is therefore probably a dimer of the 19-kDa oleosins that is formed in high salt environments. A model of the general structure of oleosins is proposed whereby the central hydrophobic domain of the protein with a predominantly beta-strand structure is embedded into the non-aqueous phase of lipid-bodies. This hydrophobic region is flanked by putative alpha-helical structures in the polar N- and C-terminal domains which are probably oriented at the lipid-water interface.

Amino Acid Sequence↗
PubMed1992

Cloning and characterisation of an oleosin gene from Brassica napus.

The sequence of an oleosin gene from Brassica napus has been determined. This gene contains a single intron of 437 bp and encodes a polypeptide of 195 amino acids. The oleosin gene product has an estimated molecular mass of 21.5 kDa and consists of a highly hydrophobic central domain flanked by relatively polar N- and C-terminal domains. The central domain is highly conserved between all oleosins sequenced to date and contains a run of periodically spaced leucine residues similar to that of a leucine-zipper motif. The gene has been shown to be expressed specifically in the embryo, maximally between 9 and 11 weeks after flowering, i.e. during the seed desiccation stage. Two transcriptional start sites have been mapped to -70 and -21 of the ATG and a putative ABA-responsive element and three repeated motifs have been identified in the promoter. These short promoter sequences could correspond to regulatory elements responsible for embryo-specific gene expression. Up to six genes exist in the oleosin gene family.

Amino Acid Sequence↗
PubMed1992

cDNA sequence of a sunflower oleosin and transcript tissue specificity.

Oleosins (oil body membrane proteins) of 20.5 and 18 kDa have been purified from sunflower (Helianthus annuus) seeds and polyclonal antibodies raised against them. The precipitated rabbit immunoglobulin fraction was purified by affinity chromatography on cyanogen bromide-activated Sepharose and specifically recognised polypeptides of 18 and 20.5 kDa in sunflower homogenate and oil body fractions assayed by western blotting. A near-full-length cDNA clone was isolated for the 20.5 kDa oleosin. The 694 bp cDNA contained an open reading frame of 534 bp, followed by an untranslated region of 81 bp and a poly(A) region of 70 bp. The open reading frame encoded a polypeptide of 19.8 kDa. Study of transcript localisation revealed message to be abundant in the embryo during the later stage of development and still present in the dry seed. No signal was observed in RNA prepared from expanding leaves.

Amino Acid Sequence↗
PubMed1992

Nucleotide sequence and temporal regulation of a seed-specific Brassica napus cDNA encoding a stearoyl-acyl carrier protein (ACP) desaturase.

The nucleotide sequence is reported for a cDNA containing the entire coding region of a stearoyl-ACP desaturase (EC 1.14.99.6) from Brassica napus L. cv. Jet neuf. The cDNA was obtained from a library constructed from poly(A)+ RNA purified from embryo tissue. The derived amino acid sequence demonstrates substantial similarity with those from other plant delta 9-desaturases. Comparative RNA-dot blot analyses using the delta 9-desaturase cDNA and a rapeseed oleosin cDNA as probes showed that although both these transcripts were seed-specific, they exhibited distinct patterns of temporal regulation. The desaturase message was induced by 25 days after anthesis (DAA), peaking at 45 DAA but decreasing considerably thereafter. In contrast, the oleosin transcript did not increase until 45-50 DAA, reaching a peak much later at about 70 DAA.

Amino Acid Sequence↗
PubMed1992

Sequence of an oleosin cDNA from Brassica napus.

Antibodies raised against purified rapeseed 19 kDa oleosin protein were used to screen an embryo-derived lambda gt11 expression library from Brassica napus. A near full-length cDNA clone, BnV, was isolated. The 781 bp cDNA contained an open reading frame of 549 bp followed by an untranslated region of 222 bp and a poly(A) region of 10 bp. Comparisons between this cDNA and a different oleosin cDNA previously isolated from the same library showed high degrees of sequence similarity in the central domain region and in the 3' untranslated region. Sequence similarities between the derived protein sequence of this cDNA and all other known oleosin protein sequences are discussed.

Amino Acid Sequence↗
PubMed1992

Surgical management of left coronary artery ostial atresia and supravalvar aortic stenosis.

Congenital atresia of the left main coronary artery ostium is a rare lesion, particularly when found in association with supravalvar aortic stenosis. This report describes the preoperative evaluation and surgical management of this lesion found in conjunction with a quadricuspid aortic valve in a 5-year-old child. Patch aortoplasty and left internal thoracic artery to left anterior descending coronary artery bypass were performed to correct this lesion.

Abnormalities, Multiple↗
PubMed1992

Respiratory and cardiovascular changes associated with toxic doses of a peptide antagonist of vasopressin in the rat.

SK&F 101926 is a synthetic octapeptide which was designed to promote free water excretion by antagonizing the action of antidiuretic hormone. The clinical and pathologic changes in rats resulting from lethal doses of SK&F 101926 have suggested that death is associated with respiratory failure and/or cardiovascular collapse. To define the relationships between respiratory failure, cardiovascular collapse, and death, respiratory and cardiovascular parameters were monitored in anesthetized rats following the intravenous administration of SK&F 101926 at a dosage (3 mg/kg) which resulted in 70% mortality. Within 5 min after receiving this dosage, mean arterial blood pressure was reduced to values between 30 and 40 mm Hg in all rats. This degree of hypotension was well tolerated by some rats and, consequently, was not considered to be the cause of death. Deaths occurred between 9 and 58 min after dosing and were preceded by respiratory depression involving marked reductions in respiratory rate and the lack of compensatory increases in tidal volume. At the time of respiratory arrest, heart rates remained above 200 beats/min, mean arterial blood pressure remained between 30 and 40 mm Hg, and there were no consistent changes in dynamic lung compliance or total pulmonary resistance. Pretreatment of rats with a mast cell stabilizing agent (disodium cromoglycate), a mast cell degranulating agent (compound 48/80), or a histamine/5-hydroxytryptamine blocking agent (cyproheptadine) prevented the reductions in respiratory rate and death caused by SK&F 101926. These pretreatments also reduced the effect of SK&F 101926 on blood pressure, but were not able to completely prevent the hypotension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The lack of an effect of applied d.c. electric fields on peripheral nerve regeneration in the guinea pig.

This study was undertaken to provide evidence of enhanced regeneration of mammalian peripheral nerves in response to applied d.c. electric fields. Peroneal nerves of adult guinea-pigs were crushed or transected and anastomosed. Constant current d.c. stimulators (20 microA) were implanted in the flank with platinum/iridium electrodes routed to the ankles. Animals with crush lesions were tested for toe spreading ability from the 14th to the 23rd day following the lesion. Animals with transection lesions were allowed to recover for 40 days and isometric force measurements of toe abduction and foot flexion were made. Both myelinated and unmyelinated fiber densities were determined. There proved to be no difference between legs treated with an anode, a cathode, or a sham electrode as evaluated by: the time to return of the toe spreading reflex, the isometric force of either twitches or tonic contractions, the latency between stimulation and contraction, or the number or density of either myelinated or unmyelinated fibers. These negative results are at variance with other studies that have reported beneficial effects of d.c. electric fields on peripheral nerve regeneration. The stimulation and analysis techniques used in this study were well within the variety of protocols that have yielded reports of highly significant positive effects with smaller numbers of animals than used in this study. The conclusion is that either there is a subtle but highly specific and critical difference between the present protocol and others, or the other studies need to be reevaluated. In either case, it seems that the ability of applied d.c. fields to enhance peripheral nerve regeneration in vivo remains open to question.

Animals↗
PubMed1992

An overview of allocation and rationing: implications for geriatrics.

Geriatricians are faced with increasing pressure from insurers and the public to control costs. At the same time, subspecialist colleagues, patients, and the courts often demand ever more costly high-technology interventions. This conflict will only intensify given the sustained increase in the percentage of GNP spent on medical care. A number of prominent biomedical ethicists and others have explored rationing of medical care services as one response to these concerns. This is the second in a series of articles in the Journal in response to the Oregon Health Decisions Initiative and is designed to provide (1) a brief ethical perspective on rationing and allocation; (2) an analysis of our present, largely implicit, approach to rationing and allocation; and (3) some suggestions that might move the United States closer to a more coherent and reasonable means of allocating and rationing health care.

Aged↗
PubMed1992

Intratracheal aerosolization of endotoxin in the rat: a model of the adult respiratory distress syndrome (ARDS).

A technique is described for the intratracheal aerosolization of endotoxin into the rat. Using a miniaturized nozzle within the tracheal lumen to optimize uniform distribution 0.5 ml of an endotoxin solution (7 mg/kg) was aerosolized and dispersed throughout the lung. Time course studies of pulmonary function and histological changes revealed marked functional and morphological changes by 24 h. Histopathologic changes consisted of widespread pulmonary oedema and a diffuse neutrophilic alveolitis. At the same time, there were significant decreases in tidal volume, minute ventilation and lung compliance. Haematologic changes were also seen, including profound thrombocytopaenia and leukopaenia together with an increased haematocrit, indicating systemic effects in this model. Bronchoalveolar lavage (BAL) at 24 h revealed significant increases in BAL protein, erythrocytes and neutrophils. The functional, cytological and histological changes observed after endotoxin challenge mimic those seen in the Adult Respiratory Distress Syndrome in humans and can thus be used as a model to compare the efficacy of a variety of therapeutic interventions for this syndrome.

Administration, Inhalation↗
PubMed1991

Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

OBJECTIVE: A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN: Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES: Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS: Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson's chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296). CONCLUSIONS: Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.

Adolescent↗
PubMed1991

A class of amphipathic proteins associated with lipid storage bodies in plants. Possible similarities with animal serum apolipoproteins.

The lipid-storing tissues of plants contain many small (0.2-1 microns) lipid (normally triacylglycerol) droplets which are surrounded and stabilized by a mixed phospholipid and protein annulus. The proteinaceous components of the lipid storage bodies are termed oleosins and are not associated with any other cellular structures. The major oleosins of rapeseed and radish have been isolated by preparative SDS-PAGE and are respectively classes of 19 kDa and 20 kDa proteins. Both protein classes were N-terminally blocked for direct sequencing, but were partially sequenced following limited proteolytic digestion. The major rapeseed oleosin was made up of at least two 19 kDa polypeptides, termed nap-I and nap-II, which have closely related but different amino acid sequences. A single 20 kDa oleosin, termed rad-I, was found in radish. A near full length cDNA clone for a major rapeseed oleosin was sequenced and found to correspond almost exactly to the sequence of nap-II. The sequences of nap-I and rad-I show very close similarity to one another, as do the sequences of nap-II and the previously determined sequence for the major oleosin from maize. All four oleosins have a large central hydrophobic domain flanked by polar N- and C-terminal domains. Secondary structure predictions for the four oleosins are similar and a novel model is proposed based on a central hydrophobic beta-strand region flanked by an N-terminal polar alpha-helix and a C-terminal amphipathic alpha-helix. The possibility that oleosins exhibit structural and functional similarities with some animal apolipoproteins is discussed.

Amino Acid Sequence↗
PubMed1991

Usefulness of color-flow Doppler in diagnosing and in differentiating supracristal ventricular septal defect from right ventricular outflow tract obstruction.

Color-flow Doppler is used for special localization of cardiac flows. The transeptal jet in supracristal ventricular septal defect (VSD) is directed toward the pulmonary valve and is often difficult to distinguish from the right ventricular (RV) outflow tract flow. Pulsed- and continuous-wave Doppler can misread the VSD jet as a stenotic lesion in the RV outflow tract. This study describes the color-flow Doppler characteristics of supracristal VSD and determines if color-flow Doppler can differentiate supracristal VSD jets from RV outflow tract flow. The study group comprised 28 patients ranging in age from 3 days to 23 years (mean 6.4), with catheter-diagnosed supracristal VSD in 14, isolated pulmonary valve stenosis in 10 and RV infundibular obstruction in 4. The echocardiographic Doppler and color-flow Doppler data of all patients were reviewed without knowledge of catheterization diagnosis. In all patients with supracristal VSD, color-flow Doppler revealed an abnormal transeptal jet directed toward the pulmonary valve that occurred 5 to 10 ms before RV outflow tract flow was identified. VSD and RV outflow tract jet could be differentiated by pulsed- and continuous-wave Doppler alone in 10 of 14 patients (71%). In 4 patients, differentiation was possible only with color-flow Doppler and electrocardiographic gating. Associated aortic regurgitation, or a fistula, or both, were detected in 6 patients. Pulsed- and continuous-wave Doppler with or without color-flow Doppler correctly identified the level of obstruction in all patients with RV outflow tract lesions (14 of 14). Supracristal VSD jet occurs in early systole and is directed toward the pulmonary valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Comparative intraperitoneal pharmacokinetics of three platinum analogues.

The pharmakokinetic profiles of intraperitoneally infused platinum analogues were determined in 13 women exhibiting minimal residual disease following surgery and systemic chemotherapy for epithelial ovarian cancer or fallopian tube carcinoma by following the disposition of tracer doses of 195mPt radiolabel. Six patients received iproplatin, four were given cisplatin and three received carboplatin. The present data demonstrate no difference in the disposition of total platinum between these three analogues, but differences in the kinetics of free platinum may exist.

Antineoplastic Agents↗
PubMed1991

Effects of adrenergic antagonists on cocaine-induced changes in respiratory function.

Cocaine-induced changes in respiratory rate (f), tidal volume (VT), total pulmonary ventilation (VE), dynamic lung compliance (Cdyn) and total pulmonary resistance (RL) were measured in anesthetized, spontaneously breathing Sprague-Dawley rats using a whole-body plethysmograph and an esophageal manometer. Carotid arterial pressure and heart rate were simultaneously monitored. An intravenous (i.v.) dose of 10 mg/kg of cocaine was lethal in all rats tested with death resulting from respiratory failure occurring between 0.25 and 1.5 min after dosing. At an i.v. dosage of 5 mg/kg, cocaine was nonlethal, although a reduction in VE was evident during the first minute after dosing. This reduction in VE was due to a decrease in f and the lack of a compensatory increase in VT. A slight decrease in RL also became evident approximately five minutes after dosing. Pretreatment with the nonselective alpha-adrenergic antagonist phentolamine (10 mg/kg) prevented the cocaine-induced depression in VE by reducing the decrease in f and blocking the inhibition of a compensatory increase in VT. In contrast, pretreatment with the nonselective beta-adrenergic antagonist propranolol (1 mg/kg) potentiated the cocaine-induced decrease in VE by enhancing the depression of f. Pretreatment with propranolol also caused a cocaine-dependent decrease in Cdyn. At a dosage of 0.3 mg/kg, labetalol, a compound possessing both nonselective alpha- and beta 1-antagonist activity (1:7) appeared to cause only a minimal potentiation of the cocaine-induced depressions in VE and f. Pretreatment with propranolol or labetalol also resulted in the death of 20% of the rats administered 5 mg/kg of cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1991

Reduced mortality in small premature infants treated at birth with a single dose of synthetic surfactant.

A randomized controlled trial of Exosurf Neonatal, a synthetic exogenous surfactant, was performed. Exosurf was given to premature infants weighing 700-1350 g, by instillation down the endotracheal tube during mechanical ventilation, within 1 h of birth. Control infants were treated with air. Dose administration was performed in secrecy by clinicians who maintained the blind for 2 years. A total of 109 infants received air and 109 received Exosurf; 19 infants with congenital pneumonia or major malformations were excluded from the primary efficacy analysis. By the age of 28 days there were 14 deaths in the air group and 4 deaths in the Exosurf group, a 69% reduction with Exosurf (P = 0.020). Survival without bronchopulmonary dysplasia at the age of 28 days was significantly improved by 15% (P = 0.050). By the age of 1 year post-term there were 19 deaths in the air group and 10 deaths in the Exosurf group, a 42% reduction with Exosurf (P = 0.104). There were no significant changes in the incidence of bronchopulmonary dysplasia, pulmonary air leaks, intraventricular haemorrhage, patent ductus arteriosus, necrotizing enterocolitis or infection. The reduction in mortality indicates important results in high risk premature infants treated soon after birth with a single dose of Exosurf.

Bronchopulmonary Dysplasia↗
PubMed1991

The value of the autopsy in congenital heart disease.

We reviewed autopsies in 50 consecutive cases of congenital heart disease between 1980 and 1988. Autopsy results were compared to premortem clinical diagnosis. The patients ranged in age from two days to 66.5 years with a mean age of 6.42 years; 68% were less than one year of age. The most common diagnoses were hypoplastic left heart syndrome in 16 (32%) and ventricular septal defect in five (10%). Other common diagnoses included coarctation of the aorta, hypoplastic right heart syndrome, tetralogy of Fallot, transposition of the great vessels and tricuspid atresia. No patient had a missed diagnosis that would have changed survival (Class 1). Four (8%) of the patients had one missed major diagnosis that did not change their survival because they were already being symptomatically treated or because no clinical treatment was available (Class 2). The majority of autopsy derived data were missed minor diagnoses that were related [14 (28%)-Class 3] or unrelated [12 (24%) - Class 4] to the terminal disease process. However, despite the small percentage of autopsy findings that would have directly affected survival, the autopsy provided important additional clinical information in 30 (60%) patients. This information could be used to correct management errors and to develop protocols for prophylaxis against known complications. The pediatric autopsy can provide useful clinical data that may be a guide to altering clinical therapy and is essential in providing genetic counseling.

Adolescent↗