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Biomedical subjects

D J Murphy

Publications and source records attributed to D J Murphy.

At least 73 records · Page 4Linked to original sources
PubMed1997

Biochemical and site-specific effects of insulin-like growth factor I on intrinsic tenocyte activity in equine flexor tendons.

OBJECTIVE: To examine the site-specific and dose-dependent effects of insulin-like growth factor I (IGF-I) on normal equine tendon in vitro. SAMPLES: Superficial digital flexor tendon explants derived from a euthanatized 3-year-old horse. PROCEDURE: Explants in culture were treated with 0, 100, 250, or 500 ng of IGF-I/ml for 14 days with an end-stage radiolabel of 20 microCi of [3H]proline/ml or 5 microCi of [3H]thymidine/ml. The tendon tissues were then analyzed biochemically for hydroxyproline content by reverse-phase high-performance liquid chromatography, DNA content by fluorometry, and glycosaminoglycan content by the dimethylmethylene blue dye-binding assay. In addition, morphologic analysis of the explants comprised histologic examination, autoradiography, and immunohistochemistry. RESULTS: Hydroxyproline content was significantly increased in explants treated with 100 and 250 ng of IGF-I/ml. Additionally, the collagen synthetic rate, measured by incorporation of [3H]proline into hydroxyproline, was significantly increased for all treatment groups. On the basis of autoradiograms, fibroblast proliferation and collagen synthesis were predominantly confined to the endcap and adjacent endotenon of the explants. Enhanced immunoreactivity for type-I collagen, compared with type-III collagen, was evident in the treated explants, an observation supported by positive staining for type-I collagen with picrosirius red. Histologically, treated explants contained greater numbers of larger and more metabolically active fibroblasts, compared with untreated controls. CONCLUSION: IGF-I enhances collagen synthesis in normal equine flexor tendon in a dose-dependent manner. IGF-I also exerts its primary effect on cell proliferation and collagen synthesis in the epitenon and adjacent endotenon and accompanying perivascular connective tissues, consistent with enhancement of intrinsic tendon metabolism. CLINICAL RELEVANCE: IGF-I may have a potential role in the treatment of tendinitis in horses.

Animals↗
PubMed1996

An improved model for professional conferences and workshops.

A cooperative learning method designed to increase learning and other benefits to participants is presented. Small group problem-solving from case studies or story narratives provides a way to overcome the limitations of conventional lecture presentations. An example that used a case study in small groups during a breakout session at a scientific conference to improve skills in intervention design and research evaluation is described.

Congresses as Topic↗
PubMed1996

An occupational health and safety intervention research agenda for production agriculture: does safety education work?

It is clear that agriculture has not kept pace with other hazardous industries in reducing its injury rate. For example, between 1960 and 1990 the work death rate for agriculture decreased only 28% while the work death rates decreased 65% for mining and 55% for construction [Purschwitz (1992)]. A national conference in Iowa in 1988 came to the forceful conclusion that "America's most productive workforce was being systematically liquidated by an epidemic of occupational disease and traumatic death and injury" [NCASH (1988)]. In 1991, the nation's top public health officer, the U.S. Surgeon General, convened a conference titled "FarmSafe 2000-A National Coalition for Local Action," to formally address agricultural safety and health issues. Importantly, conferees recognized that preventing injury and disease was superior to trying to rehabilitate people after an injury occurred. But does participation in farm safety and health educational programs lead to a reduction in risk of injury from farm work? Questions are being raised about the value of farm safety and health educational information, campaigns, programs, and related activities. The questions have identified a critical gap in the literature of farm safety and health education. There is currently no good evidence demonstrating that farm safety and health education, campaigns, programs, or related activities lead to a relatively stable reduction of risk on the farm. In other words, do farmers and their families actually put to use, in a relatively permanent or stable manner, the educational information regarding elimination, reduction, or control of physical hazards and the modification of work behavior that may cause injury?

Agriculture↗
PubMed1996

Characterization of anther-expressed genes encoding a major class of extracellular oleosin-like proteins in the pollen coat of Brassicaceae.

A large, heterogeneous, highly expressed gene family encoding oleosin-like proteins is described in the Brassicaceae. Seven related cDNA sequences were isolated from Brassica napus anther mRNA using RACE-PCR and compared with other recently described anther-specific oleosin-like genes from B. napus. The expression patterns of four representative members of this diverse gene family were analyzed by Northern blotting and in situ hybridization. In all cases, the genes were expressed specifically in the tapetum of 3-5 mm B. napus buds, which contained microspores at the late-vacuolate and bicellular stages of development. The predicted protein products are ordered into subclasses, each of which has a characteristic C-terminal domain, containing different amino acid motifs or repeated residues. Tryphine (pollen coat) fractions from mature B. napus pollen were found to be particularly enriched in polypeptides of apparent molecular weights 32-38 kDa, plus numerous less abundant polypeptides of less than 15 kDa. The N-terminal 15-20 residues of three of these polypeptides (12, 32 and 38 kDa) were found by microsequencing to be identical to parts of the predicted amino acid sequences of three of the tapetal-expressed oleosin-like genes. This indicates the possibility of post-translational modification of these proteins resulting in a cleavage of the primary translation products in order to generate the mature tryphine polypeptides. These data imply that a large and diverse group of oleosin-like proteins is synthesized in the tapetum of B. napus anthers and that following tapetal degradation, these proteins, possibly in modified form, then relocate to the developing microspores where they eventually constitute some of the major components of the extracellular tryphine of mature pollen grains. These proteins share a conserved 70 amino acid residue hydrophobic domain and are related structurally to the seed-specific intracellular oleosins, although their biological function may be different.

Amino Acid Sequence↗
PubMed1996

Ultrasound findings and clinical antecedents of cerebral palsy in very preterm infants.

OBJECTIVE: To investigate the incidence and timing of neonatal ultrasound lesions, and clinical details about pregnancy and the perinatal period, in a total population of extremely premature children with cerebral palsy, born to mothers who were resident in Oxfordshire. METHODS: Eighteen children born at less than 32 completed weeks of gestation were identified from a regional cerebral palsy register. Eighteen controls were matched for gestation, time, and place of birth. Perinatal records and ultrasound reports were systematically reviewed. Sequential neonatal ultrasound images stored on videotape were reanalysed, blind to the outcome of the infants. RESULTS: Sixteen (89%) of the cerebral palsy cases and one (6%) control had parenchymal cysts on neonatal brain scans. Of the cerebral palsy cases, none had cysts detectable on the first day. Six developed cysts within the first 10 days of life, and two of these had periventricular echodensities when first scanned postnatally. Antenatal complications were recorded in 16 cases and nine controls. The early postnatal appearance of cysts in a few babies with a history of severe antenatal complications suggested that antenatal factors may have contributed to the cerebral pathology. CONCLUSIONS: Intrauterine factors may have contributed to adverse neurological outcome, but 16/18 of the preterm cerebral palsy cases had an associated cerebral lesion which developed in the perinatal period.

Brain Diseases↗
PubMed1996

Clinical associations and time of onset of cerebral white matter damage in very preterm babies.

Neuropathological examinations were carried out at necropsy on 83 very pre-term babies who died during their first hospital admission. Forty seven (57%) babies had evidence of cerebral damage-39 with ischaemic white matter damage. The time of onset of ischaemic lesions was thought to be prenatal in 12 cases (31%) and postnatal in a further 12 (31%). The exact timing of damage could not be determined in 15 (38%) cases. Maternal and neonatal case notes were reviewed to ascertain clinical associations of ischaemic white matter damage. There were no clear associations between adverse clinical factors and prenatal ischaemic white matter damage. In contrast, pre-eclampsia, intrauterine growth retardation, and delivery without labour were associated with postnatal damage as were neonatal sepsis, necrotising enterocolitis, and seizures. The absence of a clear association between the timing of adverse clinical factors and the timing of ischaemic cerebral damage suggests that cerebral damage in very preterm babies may result from a sequence of events rather than one specific insult.

Brain↗
PubMed1995

Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies.

The increase in survival of very preterm babies during the 1980s was accompanied by a sharp increase in the rate of cerebral palsy in this group. The relation between antenatal and intrapartum factors and cerebral palsy in such babies has not been well defined. To identify adverse and protective antenatal and intrapartum factors we undertook a case-control study of 59 very preterm babies who developed cerebral palsy, identified from a population-based register, and 234 randomly selected controls. The frequency of cerebral palsy decreased with increasing gestational age and birthweight. Antenatal complications occurred in 215 (73%) of the women with preterm deliveries. Factors associated with an increased risk of cerebral palsy after adjustment for gestational age were chorioamnionitis (odds ratio 4.2 [95% CI 1.4-12.0]) prolonged rupture of membranes (2.3 [1.2-4.2]), and maternal infection (2.3 [1.2-4..5]). Pre-eclampsia was associated with a reduced risk of cerebral palsy (0.4 [0.2-0.9]), as was delivery without labour (0.3 [0.2-0.7]). There was no increased risk of cerebral palsy with intrauterine growth retardation (1.0 [0.9-1.1]). The effect of rigorous management of adverse antenatal factors on the frequency of cerebral palsy in very preterm babies should be tested in randomised controlled trials.

Apgar Score↗
PubMed1995

Revisiting ground-state and transition-state effects, the split-site model, and the "fundamentalist position" of enzyme catalysis.

In 1978 Schowen laid out the "fundamentalist position" of enzyme catalysis: "...the entire and sole source of catalytic power is the stabilization of the transition state; reactant-state interactions are by nature inhibitory and only waste catalytic power." In 1992 Menger developed the "split-site model" in order to demonstrate contradictions of the fundamentalist position. One of Menger's examples is recounted in which the energy of the enzyme-substrate complex (delta GES) is lowered, yet the catalytic rate increases, incompatible with the claim that reactant- (i.e., ground-) state interactions are inhibitory. A rigorous definition of ground-state effect is proposed which resolves the apparent contradictions. A ground-state effect (delta delta GES) is defined as one in which the energy of the ground state has changed, but the energy of the catalyzed transition state is unchanged when one enzyme is compared to another. This is a result of the constraint that the free energy of binding of the enzyme to the uncatalyzed reaction transition state, delta Gb*, is constant. That ground-state interactions are inhibitory when a single enzyme-catalyzed reaction is considered has been proven by Schowen: this definition of ground-state effect achieves the result of making additional ground-state interactions inhibitory also. This definition is rather restrictive, however, and does not describe many of the possible changes in enzyme energy levels. A proposal is therefore put forth to simply explain the changes in terms of alterations in intrinsic and utilized binding energy.

Catalysis↗
PubMed1995

A non-invasive method for distinguishing central from peripheral nervous system effect of respiratory depressant drugs in conscious rats.

1. A simple, non-invasive method for distinguishing the central from peripheral effects of respiratory depressant drugs was developed in conscious rats. 2. The procedure involves exposing rats for 5 min to an air mixture containing 8% CO2 (central stimulant) followed by an i.v. bolus injection of 300 micrograms/kg sodium cyanide (peripheral stimulant) and comparing the changes in minute volume and mean inspiratory flow (respiratory drive) before and after drug treatment. 3. The central depressant drugs morphine, xylazine, L-2-phenylisopropyladenosine (L-PIA) and gamma-hydroxybutyric acid. (GHBA) inhibited the CO2-induced increase in minute volume and enhanced the sodium cyanide-induced increase in mean inspiratory flow. 4. Peripheral depression produced by carotid body denervation had no effect on the CO2-induced increase in minute volume and inhibited the sodium cyanide-induced increase in mean inspiratory flow.

Animals↗
PubMed1995

The mortality and morbidity associated with umbilical cord prolapse.

OBJECTIVE: To examine the management of cord prolapse and its morbidity and mortality. DESIGN: Retrospective study of consecutive babies born after cord prolapse, identified using the Oxford Obstetric Data System, and those with registered handicap, identified by the Oxford Region Register of Early Childhood Impairments. SETTING: District maternity hospital managing more than 6000 deliveries annually. SUBJECTS: One hundred and thirty-two babies born after the identification of cord prolapse in the John Radcliffe Hospital between January 1984 and December 1992. MAIN OUTCOME MEASURES: Survival rates, condition at birth assessed by Apgar scores at 1 and 5 minutes and blood gas values on cord blood samples, and incidence of major handicap at three years of age. RESULTS: The incidence of cord prolapse was 1 in 426 total births. There were six stillbirths and six neonatal deaths. One baby died as a result of birth asphyxia. The uncorrected perinatal mortality rate was 91 per 1000. Of 120 survivors, only one baby was known to suffer a major neurological handicap. Electronic cardiotocographs aided the diagnosis of cord prolapse in 41% of cases. Apgar scores were better with a shorter diagnosis to delivery interval, but cord gas results did not correlate well with Apgar scores or the diagnosis to delivery interval. CONCLUSIONS: Cord prolapse occurs with a relatively stable incidence in this population irrespective of changes in obstetric practices. Despite the high incidence of ominous cardiotocographs, low Apgar scores and acidaemia on blood gas analysis, the fetal outcome is not as poor as might be expected and mortality is predominantly attributable to congenital anomalies and prematurity rather than birth asphyxia.

Cardiotocography↗
PubMed1994

The influence of the probability of survival on patients' preferences regarding cardiopulmonary resuscitation.

BACKGROUND: Studies suggest that a majority of elderly patients would want to undergo cardiopulmonary resuscitation (CPR) if they had a cardiac arrest. Yet few studies have examined their preferences after clinicians have informed them about the outcomes of CPR. METHODS: To study older patients' preferences regarding CPR, we interviewed as many ambulatory patients as possible in one geriatrics practice in Denver from August 1, 1991, through July 31, 1992. RESULTS: A total of 371 patients at least 60 years of age were eligible; 287 completed the interview (mean age, 77 years; range, 60 to 99). When asked about their wishes if they had cardiac arrest during an acute illness, 41 percent opted for CPR before learning the probability of survival to discharge. After learning the probability of survival (10 to 17 percent), 22 percent opted for CPR. Only 6 percent of patients 86 years of age or older opted for CPR under these conditions. When asked about a chronic illness in which the life expectancy was less than one year, 11 percent of the 287 patients opted for CPR before learning the probability of survival to discharge. After learning the probability of survival (0 to 5 percent), 5 percent said they would want CPR. CONCLUSIONS: Older patients readily understand prognostic information, which influences their preferences with respect to CPR. Most do not want to undergo CPR once a clinician explains the probability of survival after the procedure.

Advance Directives↗
PubMed1994

Extragenital adenosarcoma arising in the pouch of Douglas.

We describe a rare case of extrauterine adenosarcoma, the first arising in the Pouch of Douglas, in a 49-year-old premenopausal woman with an elevated CA 125. The tumor consisted of benign glandular and malignant stromal elements. There was no associated endometriosis. Previously reported cases of extragenital adenosarcomas are reviewed.

Adenosarcoma↗
PubMed1994

A seed-specific Brassica napus oleosin promoter interacts with a G-box-specific protein and may be bi-directional.

In Brassica napus, oleosins are expressed at high levels in the seed during the latter stages of embryo development. The cis-acting regulatory properties of an 872 bp promoter fragment of a B. napus oleosin gene were examined by analysis of beta-glucuronidase (GUS) expression in transgenic tobacco plants containing an oleosin promoter-GUS transcriptional fusion. The reporter gene was expressed at high levels only in seeds, specifically in embryo and endosperm tissue and regulated throughout seed development. These data demonstrate that oleosin gene transcription is regulated in a tissue-specific and temporally regulated manner and clearly indicate that oleosin protein expression is co-ordinated primarily at the transcriptional level. Oleosin mRNA was shown to be abscisic acid (ABA) inducible and an ABA-response element in the oleosin promoter was shown to be bound by a protein factor in a sequence-specific manner. Sequence analysis of the oleosin promoter has identified several other putative cis-acting sequences which may direct oleosin gene expression. The presence of a large open reading frame in the bottom strand of the oleosin promoter (ORF2) which encodes a polypeptide similar to the ethylene-induced E4 gene of tomato is reported. A PCR-generated DNA probe containing the ORF2 sequence hybridised with a 1.4 kb transcript in total RNA extracts of a variety of tissues, including leaves and germinated seed cotyledons. This finding suggests that the oleosin gene promoter directs transcription in both directions. It is the first report of a bi-directional nuclear gene promoter in plants.

Amino Acid Sequence↗