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Biomedical subjects

M Hayes

Publications and source records attributed to M Hayes.

At least 19 recordsLinked to original sources

Isolation and characterization of four CSF-1-dependent placental macrophage cell lines.

By selection and cloning in the presence of colony-stimulating factor 1 (CSF-1), we have obtained from separate explants of individual 12- or 13-day mouse placentas four clonal cell lines dependent on CSF-1 for survival and growth in culture. All four cell lines show characteristics consistent with their derivation from placental macrophages. We describe the effects of CSF-1 on growth, morphology, and CSF-1 receptor phosphorylation. One cell line, JPL2A, which shows relatively complete growth arrest in the absence of CSF-1, was characterized in detail with respect to the effects of CSF-1 on DNA synthesis and protein turnover and its response to the duration of CSF-1 stimulation. In contrast to previous studies, our results suggest that extended stimulation leads to continuous recruitment of cells competent to reenter the cell cycle. These findings are discussed in terms of growth factor effects on the cell cycle and the usefulness of these cell lines for further study of growth factor signal transduction in macrophages.

Animals

The relationship between cardiac reserve and survival in critically ill patients receiving treatment aimed at achieving supranormal oxygen delivery and consumption.

The relationship between survival and cardiac responsiveness to therapy aimed at achieving supranormal values for cardiac index, oxygen delivery and oxygen consumption (cardiac index (CI) > 4.5 l/min/m2, oxygen delivery (DO2) > 600 ml/min/m2, and oxygen consumption (VO2) > 170 ml/min/m2), has been investigated in a heterogeneous group of critically ill patients. Thirty-two patients were prospectively studied and divided into survivors and non-survivors. Cardiac reserve was assessed by determining changes in CI, left ventricular stroke work index (LVSWI) and cardiac power output (CPO) in response to optimal fluid administration and inotropic stimulation with dobutamine. On admission LVSWI and CPO were significantly higher in survivors (P < 0.05), despite no significant differences in pulmonary artery occlusion pressure (PAOP). In response to fluid CI, CPO and LVSWI increased significantly in survivors (P < 0.01), but not in non-survivors. Following optimal fluid administration, survivors achieved significantly higher values for CI, LVSWI (P < 0.01), and CPO (P < 0.001) than non-survivors. At maximum resuscitation all three variables were significantly higher in survivors than in non-survivors (P < 0.001). The dose of dobutamine administered to non-survivors (median (range) 100 (5-200)) was significantly greater (P < 0.001) than that given to the survivors (median (range) 10 (0-25)). The dose of dobutamine was limited by complications in 12 of the non-survivors. These observations suggest that cardiac reserve is an important determinant of outcome following critical illness. In unresponsive patients attempts to achieve supranormal oxygen delivery and consumption with massive inotropic support may not only be ineffective but frequently precipitates tachydysrhythmias and myocardial ischaemia.

Adult

Determination of CGS 16617 and stable isotope-labeled CGS 16617, an angiotensin-converting enzyme inhibitor, in human plasma by gas chromatography/mass spectrometry.

An analytical method has been developed for the simultaneous determination of a novel orally active angiotensin-converting enzyme inhibitor (CGS 16617) and a stable isotope-labeled analog. Both compounds are isolated from human plasma using an ion-exchange column, derivatized with pentafluoropropionic anhydride and pentafluoropropanol, and analyzed by gas chromatography/mass spectrometry. After splitless injection on a methyl-silicon column, the compound is detected using negative ion chemical ionization with nitrous oxide as a reagent gas. CGS 16617 labeled with four deuteriums and two 13C is used as an internal standard. The accuracy and precision of the method, expressed as the overall mean +/- SD recovery obtained from two sets of 36 quality-control samples used during a clinical study (concentration range 0.2-100 ng ml-1 plasma), was 96.1 +/- 16.2% for unlabeled drug and 97.6 +/- 14.4% for the D4-labeled drug (concentration range 0.2-100 ng ml-1 plasma). The limit of quantification using 1 ml plasma is 0.2 ng ml-1 for both labeled and unlabeled drug.

Angiotensin-Converting Enzyme Inhibitors

Antenatal prediction of mother-infant difficulties.

A prospective study of 143 "low risk" pregnant women expecting their first baby was conducted in Newcastle, Australia. The study was designed to examine the contribution of a woman's perception of her own childhood experiences, her trait anxiety level, socioeconomic status, and social support network to difficulties in her relationship with her baby during the baby's first year. The women were initially interviewed during pregnancy and followed up 3 and 12 months postpartum. Follow-up measures included the Dimensions of Perinatal Adjustment, the Neonatal Perception Inventory, the Ainsworth Strange Situation, and information from hospital records, family doctors, and baby health centre sisters. Women who perceived their social network as less supportive during pregnancy were likely to see their one-year-old babies (p less than .05) as more difficult. The other antenatal measures were not significantly predictive of outcome.

Adolescent

Transgenic expression of a variant of human tissue-type plasminogen activator in goat milk: purification and characterization of the recombinant enzyme.

A glycosylation variant of human tissue-type plasminogen activator (tPA) designated longer-acting tissue-type plasminogen activator (LAtPA) was extensively purified from the milk of a transgenic goat by a combination of acid fractionation, hydrophobic interaction chromatography and immunoaffinity chromatography. This scheme provided greater than 8,000-fold purification of the protein, a cumulative yield of 25% and purity greater than 98% as judged by SDS gel electrophoresis. SDS gel electrophoresis revealed that the transgenic enzyme was predominantly the "two chain" form of the protease. The specific activity of the purified transgenic protein, based on the average of the values obtained for three different preparations, was 610,000 U/mg as judged by amidolytic activity assay. This was approximately 84% of the value observed for the recombinant enzyme produced in mouse C127 cells. Analysis of the transgenic protein indicated that it had a significantly different carbohydrate composition from the recombinant enzyme produced in C127 cells. Molecular size analysis of the oligosaccharides from the transgenic and C127 cell-derived LAtPA preparations confirmed their differences and showed that the mouse cell-derived preparation contained larger, complex-type N-linked oligosaccharide structures than the material produced in goat mammary tissue.

Animals

Efficient translation of synthetic and natural mRNAs in an mRNA-dependent cell-free system from the dimorphic fungus Candida albicans.

An mRNA-dependent cell-free translation system has been developed from the human pathogenic fungus Candida albicans using either S30 or S100 lysates prepared from glass-bead-disrupted whole cells. Translation of the synthetic template poly(U) in this system is highly efficient at temperatures up to 37 degrees C and is ATP-dependent. Studies using a range of elongation-specific inhibitors suggest that the mechanism of translational elongation in C. albicans is similar to that of another yeast, Saccharomyces cerevisiae. A micrococcal-nuclease-treated C. albicans S100 lysate was able to translate exogenously-supplied homologous mRNAs, and a range of heterologous natural mRNAs, using an initiation mechanism that is inhibited by the antibiotic edeine and the 5' cap analogue 7-methylguanosine 5'-monophosphate (m7GMP). As with cell-free lysates prepared from S. cerevisiae, the C. albicans lysate is unable to initiate translation upon natural mRNAs at temperatures above 20 degrees C.

Adenosine Triphosphate

Induction of neurite outgrowth by v-src mimics critical aspects of nerve growth factor-induced differentiation.

PC12 cells treated with nerve growth factor (NGF) or infected with Rous sarcoma virus differentiate into sympathetic, neuronlike cells. To compare the differentiation programs induced by NGF and v-src, we have established a PC12 cell line expressing a temperature-sensitive v-src protein. The v-src-expressing PC12 cell line was shown to elaborate neuritic processes in a temperature-inducible manner, indicating that the differentiation process was dependent on the activity of the v-src protein. Further characterization of this cell line, in comparison with NGF-treated PC12 cells, indicated that the events associated with neurite outgrowth induced by these two agents shared features but could be distinguished by others. Both NGF- and v-src-induced neurite outgrowths were reversible. In addition, NGF and v-src could prime PC12 cells for NGF-induced neurite outgrowth, and representative early and late NGF-responsive genes were also induced by v-src. However, unlike NGF-induced neurite growth, v-src-induced neurite outgrowth was not blocked at high cell density. A comparison of phosphotyrosine containing-protein profiles showed that v-src and NGF each increase tyrosine phosphorylation of multiple cellular proteins. There was overlap in substrates; however, both NGF-specific and v-src-specific tyrosine phosphorylations were observed. One protein which was found to be phosphorylated in both the NGF- and v-src-induced PC12 cells was phospholipase C-gamma 1. Taken together, these results suggest that v-src's ability to function as an inducing agent may be a consequence of its ability to mimic critical aspects of the NGF differentiation program and raise the possibility that Src-like tyrosine kinases are involved in mediating some of the events triggered by NGF.

Cell Count

The risk approach in diarrheal disease intervention in Grenada.

In a previous paper (Soc. Sci. Med. 23, 995-1002, 1986), we described the development of a method for identifying households at high risk of childhood diarrhea based on a logit analysis of data collected as part of a diarrhea disease control project in Grenada. In this paper, we report the results of a follow-up study designed to replicate the first using data on diarrhea incidence and risk factors collected in a different set of rural communities in Grenada. The findings of the first study were not replicated. There was no significant association between the risk factors and diarrhea in the follow-up study in contrast to the very strong associations found in the first study. As a consequence, it was not possible to construct a logit model from the second data set. The possible reasons for the contrasting sets of results and their implications for the application of the risk approach are discussed with reference to a two by two true-false table.

Diarrhea

An approach to the estimation of growth standards: the univariate case.

This paper shows how reference values can be determined when the underlying characteristic (say, weight) follows a distribution that is not too distant from the Gaussian. Application of the normalizing Box-Cox power transformation is the basis of our approach. This transformation is monotonic and hence invertible, so offering the choice of two scales of measurement on which to work--the original and the Gaussian. Modified versions of the procedure are provided allowing use of the basic transformation in the presence of certain deficiencies in the data, principally measurement error and misclassification. It is shown that application of Box-Cox to a cohort at several points in time can be quite revealing. When the data are already symmetrical the Box-Cox transformation has no effect: in this case the John-Draper modulus transformation and modifications of it are shown to be helpful. All of this is illustrated by using data from the Swedish Longitudinal Growth Study.

Female

Unusual clinical presentations of intermediate lymphocytic lymphoma.

Three patients with previously unreported presentations of the follicular or mantle zone variant of intermediate lymphocytic lymphoma are described. In each case lymph node histopathology showed the presence of non-neoplastic follicular structures containing germinal centre-like areas and widened mantle zones in which the component small lymphocytes consisted of an admixture of a typical lymphoid cells. The nuclear contour of these cells was irregular or indented and they expressed an IgM lambda phenotype. The patients were typical in being over 50 years of age, anaemic with stage IV disease by virtue of bone marrow involvement, and having generalized lymphadenopathy and marked hepatosplenomegaly. Conversely, the clinical features in each case were unusual, being the nephrotic syndrome due to mesangioproliferative glomerulonephritis in one, extensive lymphomatous involvement of the ileum in the second, and recurrent pneumonia and abscess formation in the third. These associations are further examples of the way in which patients with this unusual lymphoma may present.

Aged

Clinical spectrum and outcome of neonatal convulsions.

The clinical spectrum and outcome of neonatal convulsions within an obstetric hospital population were reviewed for the 5 years, 1978-82, inclusive. There were 156 convulsing neonates managed at the Mater Mothers Hospital (110 inborn, 46 outborn). The incidence of early neonatal convulsions for inborn babies was 3.0/1000 live births. Antenatal and perinatal risk factors were compared between the 156 convulsing infants and the 36,082 infants born during the same period who did not convulse. The leading risk factors for convulsions were prematurity, intra-uterine growth retardation, low 5 min Apgar score, pre-eclampsia, antepartum haemorrhage, twin pregnancy and breech presentation. The predominant seizure type was tonic in 28.6%, multifocal clonic in 27.2%, subtle in 18.4%, myoclonic in 15.0% and focal clonic in 8.8%. Mortality (31%) and long-term disability (43%) rates were high. Tonic seizures had the highest mortality and morbidity. Throughout the duration of the study period infants received increasingly thorough investigation. Causative factors were determined in 95% of convulsing infants, most frequent being hypoxic-ischaemic encephalopathy (40.3%) and cerebroventricular haemorrhage (30.5%). Follow-up data on 99 of the 107 survivors (93%) revealed severe disability in 25, moderate disability in eight and mild disability in 10. A poor long-term prognosis was associated with prolonged convulsions, tonic and multifocal clonic convulsions, convulsions due to asphyxia and cerebroventricular haemorrhage and an abnormal neurological examination at discharge.

Humans

Helping themselves.

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Community Health Nursing