Search PubMed⌕ Search

Biomedical subjects

M A Murray

Publications and source records attributed to M A Murray.

At least 55 records · Page 3Linked to original sources

Self-predictions of emotional response patterns: age, sex, and situational determinants.

A total of 407 males and females in 4 different age groups (M age = 8.0, 10.8, 15.2, and 20.3 years) completed questionnaires requiring self-ratings of 5 emotions (angry, happy, sad, fearful, and loving), on a 5-point scale, for 10 affect-laden sentences. Each of the 5 emotions was targeted as a key emotion by 2 sentences. The resulting patterns indicate that children as young as 8 can discriminate between affect-eliciting statements, differentially rate up to 5 concurrent emotional responses, and predict response patterns similar to those predicted by adults. Furthermore, sex differences occur during adolescence whereby males predict more varied but less intense secondary emotions, whereas females predict fewer but more intense secondary emotions.

Adolescent↗

Differences in intrapartum obstetric care provided to women at low risk by family physicians and obstetricians.

To determine differences in practice style and to examine maternal and neonatal outcomes, we reviewed the hospital charts of 1115 women admitted by family physicians and 1250 women admitted by obstetricians who gave birth at one of three teaching hospitals in Toronto between April 1985 and March 1986. All the women in the two groups were categorized retrospectively as being at low risk at the onset of labour on the basis of their prenatal records and their admission histories and physical examination results. There were higher proportions of younger women and women of lower socioeconomic status in the family physician group than in the obstetrician group (p less than 0.001). The rates of interventions, including artificial rupture of the membranes, induction, augmentation, low forceps plus vacuum extraction, episiotomy and epidural anesthesia, were all higher in the obstetrician group. The mean birth weight and the cesarean section rate were the same in the two groups. Differences in labour and delivery outcomes between the two groups, including a higher rate of spontaneous vaginal delivery for the family physicians, reflected a more "expectant" practice style by family doctors. However, there were no significant differences in the rates of maternal or neonatal complications. A practice style characterized by a higher rate of interventions was not associated with improved maternal or newborn outcome in this low-risk setting.

Adult↗

Cromakalim-induced relaxation of guinea-pig isolated trachealis: antagonism by glibenclamide and by phentolamine.

1. Tested against the spontaneous tone of guinea-pig isolated trachealis, cromakalim (0.1-100 microM), isoprenaline (1 nM-1 microM) and theophylline (1 microM-1 mM) each produced concentration-dependent relaxation. 2. Glibenclamide (0.1-10 microM) did not itself alter the spontaneous tone of the trachea nor did it modify the relaxant actions of isoprenaline or theophylline. In contrast, glibenclamide (0.1 and 1 microM) caused a concentration-dependent rightward shift of the log concentration-effect curve of cromakalim. Glibenclamide (10 microM) reduced the slope of the log concentration-effect curve of cromakalim and moved the foot of the curve back towards the control position. 3. Phentolamine (1, 10 and 100 microm) did not itself alter the spontaneous tone of the trachea nor did it modify the relaxant actions of isoprenaline or theophylline. In contrast phentolamine caused concentration-dependent depression of the log concentration-effect curve of cromakalim. 4. Neither prazosin (1 microM) nor yohimbine (10 microM) modified the spontaneous tone of the trachea. Prazosin and yohimbine each failed to antagonise the effects of cromakalim, isoprenaline and theophylline. 5. Intracellular electrophysiological recording showed that glibenclamide (1 microM) and phentolamine (100 microM) caused minor change in the resting membrane potential of trachealis cells. Slow wave activity was slightly depressed by these agents. In contrast tetraethylammonium (TEA; 8 mM) caused marked depolarisation, and promoted the conversion of slow waves into regenerative action potentials. These electrical changes were accompanied by tonic tension development. 6. Phentolamine (100 microM) and glibenclamide (1 microM) reduced and reversed both the relaxation and the hyperpolarisation induced by cromakalim (10 microM). 7. It is concluded that glibenclamide and phentolamine each provide selective antagonism of the relaxant action of cromakalim in guinea-pig trachealis. These agents also inhibit the plasmalemmal hyperpolarisation induced by cromakalim. The effect of phentolamine is unrelated to the blockade of alpha 1- or alpha 2-adrenoceptors. If either glibenclamide or phentolamine act to block the K+ channels opened by cromakalim, then such channels are not identical to those which endow the trachealis plasmalemma with its powerful rectifying behaviour.

Animals↗

The guidance of axons from transplanted neurons through aneural Drosophila wings.

The sensory neurons of the wing of Drosophila arise during the first 24 hr of metamorphosis, and their axons converge to form a stereotyped set of nerves projecting proximally from the peripherally located cell bodies through the wing and towards the CNS. To better characterize the cues guiding this stereotyped axon outgrowth, we have performed a series of transplantation studies in which neurons from a variety of sources (wing, eye, antenna, and leg disks) were placed into mutant, aneural wings. Axons growing from such implants in effect assay the host wing for the presence and location of guidance cues. Our results show, first, that such axons prefer to grow in the normal, proximal direction and, second, that they prefer to grow along the approximate site of one of the normal nerves, that of the third longitudinal vein. It therefore appears that the aneural wing epithelium contains cues capable of directing both the polarity and the location of axonal outgrowth. These cues are relatively non-specific, in that a variety of neuronal types are capable of responding to them.

Animals↗

Slow tight binding inhibitors of angiotensin converting enzyme.

We have found that apparent Ki values of some, but not all, carboxyalkyl-dipeptide inhibitors of angiotensin converting enzyme decrease as a function of incubation time. The most potent of the ACE inhibitors tested so far is RAC-X-65 (N-[1(S)-carboxy-3-carboxanilidiopropyl]-L-Ala-L-Pro). When RAC-X-65 is not preincubated with human serum ACE (2.4 X 10(-11) M), the apparent Ki value is 4.4 X 10(-10) M. Preincubation of RAC-X-65 with ACE for 15 min before addition of substrate yields an apparent Ki of 4.1 X 10(-11) M. a 90 min preincubation of the inhibitor with ACE yields an apparent Ki of 1.2 X 10(-11) M, i.e., the reaction of the inhibitor with enzyme is virtually stoichiometric. The enzyme:inhibitor complex is poorly separated by molecular sieve chromatography or by dilution. That such tightly bound complexes are formed in vivo is suggested by the following results: The intravenous ED50 (anesthetized rats) of RAC-X-65 is 9.43 nmol/kg, and the time for half recovery (t1/2) of responsiveness to i.v. angiotensin I, 120 ng/kg, following a cumulative dose of 240 nmol/kg of the inhibitor is 165 min. For comparison, the i.v. ED50 of captopril is 105 nmol/kg, and its t1/2 following a cumulative dose of 240 nmol/kg is 16 min. Implied is the possibility that slow tight binding inhibitors of ACE may be used in a 1 pill per day regimen for the treatment of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Neuron differentiation and axon growth in the developing wing of Drosophila melanogaster.

Sensory neurons in the wing of Drosophila originate locally from epithelial cells and send their axons toward the base of the wing in two major bundles, the L1 and L3 nerves. We have estimated the birth times of a number of identified wing sensory neurons using an X-irradiation technique and have followed the appearance of their somata and axons by means of an immunohistochemical stain. These cells become immunoreactive and begin axon growth in a sequence which mirrors the sequence of their birth times. The earliest ones are born before pupariation and begin axonogenesis within 1 to 2 hr after the onset of metamorphosis; the last are born and differentiate some 12 to 14 hr later. The L1 and L3 nerves are formed in sections, with specific neurons pioneering defined stretches of the pathways during the period between 0 and 4 hr after pupariation (AP), and finally joining together around 12 hr AP. By 16 hr AP the adult complement of neurons is present and the adult peripheral nerve pattern has been established. Pathway establishment appears to be specified by multiple cues. In places where neurons differentiate in close proximity to one another, random filopodial exploration followed by axon growth to a neighboring neuron soma might be the major factor leading to pathway construction. In other locations, filopodial contact between neighboring somata does not appear to occur, and axon pathways joining neural neighbors by the most direct route are not established. We propose that in these cases additional factors, including veins which are already present at the time of axonogenesis, influence the growth of axons through non-neural tissues.

Animals↗

Changes in mitochondrial DNA during aging.

Mitochondrial DNA (mtDNA) was isolated from liver mitochondria of rats between 2 and 24 months of age. The mtDNA was purified by cesium chloride--ethidium bromide isopycnic density gradient centrifugation. In the gradients, in addition to the two expected bands of ethidium--DNA complex, there was observed a third, more dense band (d = 1.69 g/cm3). This novel band, rarely observed in preparations from younger animals, was present in most preparations from older animals. The latter was characterized using the diphenylamine assay(s) and ascertained to contain DNA and carbohydrate components. Agarose gel electrophoresis revealed the DNA of the novel band to have a migration identical to form I mtDNA. Digestion of the novel band with the restriction endonuclease Bam HI yielded products identical to those obtained upon treatment of form I mtDNA with Bam HI. The observation of mtDNA at a density of 1.69 g/cm3 indicates the presence, predominantly in older animals, of a subclass of mtDNA molecules with altered ethidium binding properties. The significance of this mtDNA and its position in the gradient is unclear at this time.

Aging↗

Cell proliferation in denervated muscle: time course, distribution and relation to disuse.

The effects of denervation on skeletal muscle fibers have been intensively investigated, but the effects on other cell types within muscle tissue are not well understood. In the present experiments, cell proliferation was analyzed in mouse extensor digitorum longus muscles denervated for periods of one day to six weeks. Incorporation of tritiated thymidine into DNA increased 36 h after denervation, reached a maximum at a level twenty times control at 4 days, and returned towards control values by 7 days. Incorporation first increased in the endplate area, but 12 h later involved the entire muscle. Six weeks after denervation, muscles labeled at 4 days had lost 90% of the total label. Muscle disuse, produced by tetrodotoxin block of the nerve for up to 4 days, did not result in a proliferative response. Thus, cell proliferation after denervation is not a response to simple disuse, but rather to a nerve- or muscle-related mitogen. Since the response is mostly distributed throughout the entire muscle, the mitogen probably emanates from muscle fibers.

Animals↗

Cell proliferation in denervated muscle: identity and origin of dividing cells.

DNA synthesis in skeletal muscle increases dramatically during the first week after denervation. In the present study, we have characterized the dividing cells in order to assess the specificity and significance of this response to denervation. Autoradiography of [3H]thymidine-labeled denervated muscles revealed that many classes of cells were dividing, including fibroblasts (the most numerous of the labeled cells), macrophages, vascular cells, muscle satellite cells, spindle capsule cells, perineurial cells and Schwann cells. The number of labeled satellite cells accounted for no more than 10% of the dividing cells. Labeling indices of spindle capsule, perineurial and Schwann cells reached a maximum 3 days after denervation, while those of fibroblasts and macrophages peaked at 4 days. The former group of cells, which are in close contact with nerve trunks, accounted for 28% of cell division on day 3 (but only 5% on day 4) and were apparently responding to a local influence from degenerating axons. Connective tissue cells, making up the largest class of dividing cells (80% on day 4) were found throughout the muscle and appeared to proliferate in response to changes occurring along the entire length of the muscle fibers. Macrophages involved in the response were mostly resident histiocytes, since prior labeling of blood cells showed that leukocytes did not enter the muscle in substantial number after denervation. Both muscle satellite cells and connective tissue cells are essential for the functional regeneration of muscle. Thus, on the basis of overall cytologic characterization, cell division after denervation seems to represent a limited regenerative response.

Animals↗

Plasma unconjugated oestriol and unconjugated oestradiol-17 beta in late pregnancy: individual fluctuation of concentrations from day to day and every 10 minutes.

Plasma unconjugated oestriol (E3) and unconjugated oestradiol-17 beta (E2) were determined by radioimmunoassay. In ten normal women in their last month of pregnancy the individual fluctuation of E3 concentrations (mean of the coefficients of variation, CV) from day to day (over 5 days) was 15.6% (range 6.4--26.2%). The individual fluctuation of E2 determined in eight of these women was 16.9 (10.4--25.5) %. In six of the same women who had blood samples collected every 10 min (for 3 h) the individual fluctuation of E3 concentrations was 13.8 (7.0--25.1) %, and of E2 was 16.1 (11.3--26.0) %. The degree of fluctuation of E3 in individuals was in proportion to the mean concentration, unlike E2, suggesting that in clinical practice individual changes in E3 values would be as easy to interpret at low levels as at high levels. The finding that concentrations of plasma unconjugated E3 fluctuate in individuals no more than for E2 or than reported for total E3, and less than reported for 24-h urinary oestrogens, lends practical support to the theoretical preference for the assay of plasma unconjugated E3 to assess fetoplacental function.

Adult↗

Relation between the karyopyknotic index and plasma oestrogen concentrations after the menopause.

The karyopyknotic index correlated significantly (p less than 0.001) with the plasma oestradiol but not plasma oestrone concentration in 38 postmenopausal women. This ties with previous findings that postmenopausal women with superficial dyspareunia have a more severe degree of vaginal atrophy than asymptomatic women, and that oestradiol is probably more important biologically than oestrone.

Aged↗

Relation between plasma oestrone and oestradiol and climacteric symptoms.

Plasma levels of oestrone and oestradiol-17beta were determined at 20 or 30 minute intervals for up to 24 hours in 26 postmenopausal or ovariectomised women of similar age, weight, and number of years since menopause or operation. Results in women with both superficial dyspareunia and flushes were compared with those in women with flushes only, and with those in symptomless women. Women with superficial dyspareunia had significantly lower mean concentrations of plasma-oestradiol, but not of oestrone, than symptomless women. Flushes were not related to plasma-oestrogen. The implications of these findings in relation to the optimum dose of oestrogen for treating climacteric symptoms are discussed.

Adult↗