Search PubMed⌕ Search

Biomedical subjects

M Hayes

Publications and source records attributed to M Hayes.

At least 91 records · Page 5Linked to original sources

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.

Explore the source record for details and available documents.

Community Health Nursing↗

Upper Ottawa street landfill site health study.

This report describes the design and conduct of two sequential historical prospective morbidity surveys of workers and residents from the Upper Ottawa Street Landfill Site in Hamilton, Ontario. The workers study was carried out first and was a hypothesis-generating study. Workers and controls were administered a health questionnaire, which was followed by an assessment of recall bias through medical chart abstraction. Multiple criteria were used to identify health problems associated with landfill site exposure. Those problems with highest credibility included clusters of respiratory, skin, narcotic, and mood disorders. These formed the hypothesis base in the subsequent health study of residents living adjacent to the landfill site. In that study, the association between mood, narcotic, skin, and respiratory conditions with landfill site exposure was confirmed using the following criteria: strength of association; consistency with the workers study; risk gradient by duration of residence and proximity to the landfill; absence of evidence that less healthy people moved to the area; specificity; and the absence of recall bias. The validity of these associations were reduced by three principal problems: the high refusal rate among the control population; socioeconomic status differences between the study groups; and the fact that the conditions found in excess were imprecisely defined and potentially interchangeable with other conditions. Offsetting these problems were the multiple criteria used to assess each hypothesis, which were applied according to present rules. Evidence is presented that supports the hypothesis that vapors, fumes, or particulate matter emanating from the landfill site, as well as direct skin exposure, may have lead to the health problems found in excess. Evidence is also presented supporting the hypothesis that perception of exposure and, therefore, of risk, may explain the results of the study. However, based on the analyses performed, it is the conclusion of the authors that the adverse effects seen were more likely the result of chemical exposure than of perception of risk.

Adult↗

The relationship between the skin and some bacterial species occurring on it in the Merino.

Ten bacterial species were isolated from areas on the skin of Merino sheep affected by a chronic scaly condition leading to retarded wool growth. The growth requirements of the bacteria were studied and it was shown that they could multiply under the conditions prevailing on the skin if moisture was provided. All the bacteria isolated have the ability to stimulate the infiltration of round cells into the dermis, which is the essential feature of the pathological changes in the naturally affected skin. It was concluded that the bacteria have a decided aetiological role.

Animals↗

Guidelines for routine respiratory care of patients with spinal cord injury. A clinical report.

Pulmonary compromise is a leading cause of morbidity in patients with spinal cord injury (SCI). Because these patients have such complex and massive needs, routine respiratory care is not always given the priority it deserves in a rehabilitation program. Our institution established a committee to formulate guidelines for the routine respiratory care of patients in our interdisciplinary Acute Spinal Cord Injury Program. The guidelines consisted of evaluation, treatment, and teaching interventions. The purposes of the guidelines were to increase staff awareness of the need for routine, prophylactic respiratory care of patients with SCI; to be an effective teaching tool for staff, thus resulting in a reduction of respiratory complications; and also to be a teaching tool for patients and their families so that routine respiratory care could be continued in the home. After using the guidelines for over a year, we believe that the quality of the respiratory care we provide our patients with SCI has improved. The respiratory care is more comprehensive, consistent, and coordinated among disciplines.

Acute Disease↗

Macromelanosomes in the early diagnosis of neurofibromatosis.

Skin biopsies of café-au-lait macules from 34 patients with a clinical diagnosis of classical neurofibromatosis were examined histologically and ultrastructurally to determine the presence or absence of macromelanosomes in the epidermal melanocytes and keratinocytes. Sixteen of the 34 patients had macromelanosomes. The presence of macromelanosomes varied with age and ethnic background; they were detected in nine of 12 Whites, six of 10 persons of mixed ancestry, and one of two Blacks. In these populations skin biopsy is useful in early diagnosis of neurofibromatosis. However, none of 10 persons of Indian stock had macromelanosomes. Their total absence in this group may be indicative of genetic heterogeneity.

Child↗