Coagulation tests in the emergency department.
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Blood Coagulation Tests↗
Biomedical subjects
D Barnes
Publications and source records attributed to D Barnes.
Transforming growth factor beta regulates cystatin C in serum-free mouse embryo (SFME) cells.
Differential screening of a cDNA library derived from mRNA of TGF beta-treated serum-free mouse embryo (astrocyte precursor) cells isolated a strongly TGF beta-regulated mRNA that codes for cystatin C, a cysteine protease inhibitor. Increase in cystatin C mRNA level was observed within four hours after treatment with picomolar concentrations of TGF beta. The increase was reversible upon removal of TGF beta and was not prevented by cycloheximide. These results suggest that cystatin C expression may represent a developmentally regulated differentiated function of astrocytes, and also suggest that cystatin C expression may be involved in the response of brain cells to platelet release of TGF beta after trauma or injury.
Amino Acid Sequence↗
The locus of the polymorphic epithelial mucin (PEM) tumour antigen on chromosome 1q21 shows a high frequency of alteration in primary human breast tumours.
Tumour and blood leukocyte DNAs from sporadic breast cancer patients were examined for chromosome 1 loss of heterozygosity using a probe for a polymorphic epithelial mucin, PEM, which is expressed in greater than 92% of breast carcinomas as well as in normal lactating breast tissue. Expression is detected by the monoclonal antibodies (MAbs) HMFG-1, -2 and SM-3 which react with epitopes in the 20 amino-acid repeat unit of the core protein. The PEM probe has been mapped to the chromosome band 1q21, a region that is often incriminated in chromosomal rearrangements in breast tumours. Loss of heterozygosity or alteration at the PEM locus was detected in 34% of the 70 informative patients examined. Twenty of the 24 individuals showed loss of an allele, whereas 4 showed gain of an additional allele or amplification of an existing allele. Twenty-eight percent of informative cases exhibited alterations at the MS32 locus, 1q42-43, and 20% had alterations at the short arm locus MS1 at 1p33-35. These findings identify the long arm of chromosome 1 and in particular the region around the PEM gene for localization of a gene whose loss or alteration may, in some tumours, contribute to the progression of disease in breast cancer patients.
Antigens, Neoplasm↗
Glucocorticoid and thyroid hormones inhibit proliferation of serum-free mouse embryo (SFME) cells.
Mouse embryo cells derived in a serum-free medium formulation (SFME cells) do not exhibit growth crisis or chromosomal abnormalities and are nontumorigenic in vivo; these cells are also reversibly growth inhibited by serum or platelet-free plasma (Loo et al.; Science, 236:200-202, 1987). A portion of the inhibitory activity of serum could be extracted by charcoal, a procedure that removes steroid and thyroid hormones. Both L-3,5,3'-triiodothyronine (T3) and hydrocortisone inhibited growth of SFME cells in a reversible manner. The inhibitory activity of serum also was partially removed by treatment with anion exchange resin in a procedure designed to deplete serum of thyroid hormone. However, the effect of serum on untransformed SFME cells could not be prevented by addition of the antiglucocorticoid RU38486, and ras-transformed clones of SFME cells, which are capable of growing in serum-containing medium, retained inhibitory responses to glucocorticoid and, with some clonal variability, to T3. These results suggest that glucocorticoid or thyroid hormones may contribute to the inhibitory activity of serum on SFME cells, but additional factors are also involved.
Animals↗
ras and neu oncogenes reverse serum inhibition and epidermal growth factor dependence of serum-free mouse embryo cells.
Serum-free mouse embryo cells, cultured in basal nutrient medium supplemented with insulin, transferrin, epidermal growth factor, fibronectin, and high-density lipoprotein, do not exhibit growth crisis, lack detectable chromosomal aberrations, are nontumorigenic in vivo, are dependent on epidermal growth factor for survival, and are growth inhibited by serum or platelet-free plasma. These cells after transfection with the human Ha-ras or rat neu oncogenes no longer required epidermal growth factor for survival, were tumorigenic in vivo, and also proliferated in serum-containing medium. Autocrine activity capable of replacing epidermal growth factor was detected in conditioned medium from ras-transformed cultures, but little such activity was detected in medium from neu-transformed cultures. In addition, the capability of ras or neu-transformed cells to grow in serum-containing medium could not be mimicked in untransformed cells by the addition of growth factors or conditioned medium from transformed cells. These results suggest that the known structural similarity of the neu gene product to the EGF receptor is also reflected in a functional similarity by which the mutationally activated neu protein can replace the ligand-activated EGF receptor. These results also suggest that the ability of ras- and neu-transformed cells to escape the effect of the inhibitory serum activity is a nonautocrine property distinct from the acquisition of EGF autonomy.
Animals↗
Frontiers in mammalian cell culture.
For the past 60 years, fundamental discoveries in eukaryotic biology using mammalian cell cultures have been significant but modest relative to the enormous potential. Combined with advances in technologies of cell and molecular biology, mammalian cell culture technology is becoming a major, if not essential tool, for fundamental discovery in eukaryotic biology. Reconstruction of the milieu for cells has progressed from simple salt solutions supporting brief survival of tissues outside the body to synthesis of the complete set of structurally defined nutrients, hormones and elements of the extracellular matrix needed to reconstruct complex tissues from cells. The isolation of specific cell types in completely defined environments reveals the true complexity of the mammalian cell and its environment as a dynamic interactive physiological unit. Cell cultures provide the tool for detection and dissection of the mechanism of action of cellular regulators and the genes that determine individual aspects of cell behavior. The technology underpins advances in virology, somatic cell genetics, endocrinology, carcinogenesis, toxicology, pharmacology, hematopoiesis and immunology, and is becoming a major tool in developmental biology, complex tissue physiology and production of unique mammalian cell-derived biologicals in industry.
Allergy and Immunology↗
Death of serum-free mouse embryo cells caused by epidermal growth factor deprivation is prevented by cycloheximide, 12-O-tetradecanoylphorbol-13-acetate, or vanadate.
Serum-free mouse embryo cells cultured in medium supplemented with insulin, transferrin, high-density lipoprotein, and fibronectin are dependent on epidermal growth factor for survival. Cycloheximide or actinomycin D prevented cell death caused by growth factor deprivation, suggesting that cell death required the synthesis of RNA and protein, a phenomenon similar to that reported for neuronal cell death in the absence of nerve growth factor. Orthovanadate, an inhibitor of phosphotyrosine phosphatases, and 12-O-tetradecanoylphorbol-13-acetate, an activator of protein kinase C, also prevented serum-free mouse embryo cell death in the absence of epidermal growth factor.
Adenylyl Cyclases↗
Serum and transforming growth factor beta regulate glial fibrillary acidic protein in serum-free-derived mouse embryo cells.
Serum-free mouse embryo (SFME) cells, derived in medium in which serum is replaced with growth factors and other supplements, display distinctive properties: (i) SFME cells do not lose proliferative potential or show gross chromosomal aberration upon extended culture, (ii) these cells depend on epidermal growth factor for survival; and (iii) SFME cell proliferation is reversibly inhibited by serum. Treatment of SFME cells with serum or transforming growth factor beta led to the appearance of glial fibrillary acidic protein, a specific marker for astrocytes. The appearance of glial fibrillary acidic protein in cultures was reversed upon removal of transforming growth factor beta or serum. Cells with properties similar to SFME cells were also isolated from adult mouse brain. These results suggest a role for transforming growth factor beta in astrocyte differentiation in developing organisms and in response to injury and identify the cell type that has the unusual properties of SFME cells.
Animals↗
Expression of glutathione S-transferases and cytochrome P450 in normal and tumor breast tissue.
The level of expression of glutathione S-transferases (GSTs) and cytochrome P450s in breast tissue are potentially important determinants in both the susceptibility of this tissue to the mutagenic effects of chemical carcinogens and in the response of breast tumors to chemotherapy. In this study we have investigated the expression of these proteins in 41 tumor and surrounding normal breast tissue samples by measurement of substrate metabolism. Western blot analysis and immunohistochemistry. In addition, we have quantitated the concentration of alpha, mu and pi class GST subunits using radioimmunoassay. All three classes of GST were expressed in breast tissue. The pi and mu class enzymes preponderate. Both the polymorphic mu class GST as well as a further form, present in all individuals, were found in high concentration. The polymorphic mu class GST was expressed in approximately 50% of the samples, which is consistent with the frequency of this polymorphism in the population and therefore does not appear to be a factor in susceptibility to this disease. Interestingly, although levels of the alpha class GST were very low, in two tumor samples extremely high levels of the B1B1 subunit were detected. Immunohistochemical studies showed significant variability in the localization of the pi class of GST between normal epithelial cells, infiltrating plasma cells and tumor cells, and in some samples GST pi appeared to be almost absent from the tumor tissue. No direct, or inverse correlation was found between GST pi concentration determined by radioimmunoassay and estrogen receptor levels. However, when studied by immunohistochemistry estrogen receptor negative tumors did tend to have higher GST pi content. The only cytochrome P450 detectable by Western blot analysis was a member of the P450IIC gene family. This was apparently distinct from the P450IIC proteins expressed in the liver and was detected in normal and tumor tissues to a similar extent.
Adult↗
Improved physical performance outcomes after functional restoration treatment in patients with chronic low-back pain. Early versus recent training results.
Functional restoration, a medically supervised team treatment approach that addresses deficits that accompany the deconditioning process in patients with chronic low-back pain, has emerged as a viable rehabilitation alternative. While the primary emphasis of this treatment approach has remained unchanged since its inception over 6 years ago, recent rapid advances in quantification technology and understanding of the complexity of the chronic low-back pain (CLBP) syndrome have led to more sophisticated and aggressive rehabilitation efforts. In the current study, the authors examined two groups of patients with CLBP, from the treatment program's initial (n = 45) and most recent years (n = 57) of operation, respectively, to determine if the evolution of the treatment program has resulted in increased gains in physical capacity between these groups of patients. Patients in each group were assessed on measures of isokinetic trunk strength and spinal range of motion at program admission and discharge. Both groups demonstrated improved physical capacity levels, but the recent group also demonstrated considerably higher physical capacity levels than the early group, at both program admission and discharge. It was concluded that functional restoration continues to be successful with CLBP patients, and that increased preprogram training and education may facilitate a more rapid elimination of inhibitory factors (ie, pain, fear of reinjury), which often impede and slow physical training.
Adult↗
Changes in MMPI profile levels of chronic low back pain patients following successful treatment.
The present study evaluated changes in the Minnesota Multiphasic Personality Inventory (MMPI) profile levels of chronic low back pain (CLBP) patients following successful treatment for their disability. A total of 69 patients were evaluated at admission and 6 months after completing the treatment program. Results demonstrated significant decreases of the Hysteria, Depression, and Hypochondriasis scales toward normal ranges at the 6-month evaluation. These results indicate that MMPI profile levels of CLBP patients are significantly reduced to normal ranges following successful treatment.
Adult↗
Orbital optic nerve glioma in adult life.
In seven cases, optic nerve glioma presented as an expanding orbital mass in previously asymptomatic adults. Clinically and histologically, these tumors were similar to the orbital optic nerve gliomas of childhood; in contrast to the rapidly progressive malignant gliomas of the chiasm well described in adults, the patients with these tumors had a more benign clinical course. Management of optic nerve glioma in adulthood should be conservative in the presence of useful vision.
Adolescent↗
Serum-free mouse embryo cells: growth responses in vitro.
We have derived serum-free mouse embryo (SFME) cultures in a basal nutrient medium supplemented with insulin, transferrin, epidermal growth factor (EGF), high-density lipoprotein (HDL), and fibronectin. These cells are nontumorigenic, lack gross chromosomal aberrations, and exhibit several other unique properties, including dependence on EGF for survival and growth inhibition by serum. We have examined the concentration dependence of the growth stimulatory effects of protein supplements used in the SFME medium formulation and surveyed other supplements that might act as alternative or complementary additions to the culture medium. Insulin could be replaced by insulin-like growth factor I and EGF could be replaced by transforming growth factor alpha in the same concentration range. Transferrin could be replaced by higher concentrations of lactoferrin. Deterioration of cultures in the absence of EGF began within 8 hours of the removal of the growth factor, and could be prevented by the addition of fibroblast growth factor/heparin-binding growth factor. Attachment proteins other than fibronectin were effective on SFME cells, but limited success was obtained when substituting other lipid preparations for HDL. These data introduce a precise system for exploring the unusual characteristics of SFME cells and contribute additional information that may be useful in the extension of these approaches to other cell types and species.
Animals↗
Lessons from magnetic resonance imaging in multiple sclerosis.
Magnetic resonance imaging is a potent diagnostic tool in multiple sclerosis: it can reveal dissemination of lesions in both space and time in many patients with isolated neurological syndromes. Many more new lesions occur than clinical relapses. A consistent very early event is the breakdown of the blood-brain barrier which is largely repaired over weeks, leading to marked changes in the size of acute lesions. Chronic lesions show persistent oedema and enlarge through cycles of renewed peripheral activity. The vascular changes reflect inflammation: the resulting MRI changes provide, for the first time, a non-invasive means of monitoring disease activity and its modification by treatment.
Blood-Brain Barrier↗
Comparison of CT scan muscle measurements and isokinetic trunk strength in postoperative patients.
The present study compared the computed tomography (CT) scan muscle area/muscle density and isokinetic trunk strength of a group of spinal surgery patients (35 males and 11 females) 3 months postoperatively. Analyses showed trunk strength means to be below 50% of gender-specific "normal" values obtained by evaluating a normative sample. Extensor strength was more significantly affected than flexors. Single-cut CT scans performed at the time of isokinetic trunk strength assessment demonstrated psoas and erector spinae atrophy through a significant decrease in muscle density, with only a trend towards decreased cross-sectional area. Findings also indicated that there was a significant correlation between increased mechanical trunk strength performance and greater muscle density on CT scan. Strength was significantly lower for the male patients undergoing spinal fusion compared with those undergoing disc excision. However, no significant difference was found in strength measures between: males with high versus low pain level and working versus nonworking males at the time of evaluation.
Adult↗
Psychosocioeconomic predictors of treatment success/failure in chronic low-back pain patients.
The present study evaluated various psychosocioeconomic variables in chronic low-back pain (CLBP) patients being treated in a functional restoration rehabilitation program. The purpose of the study was to identify those factors that may have predictive value with respect to treatment outcome. Three groups of patients (Success, Failure, Dropout) were examined based on outcome and follow-up data 1 and 2 years after program completion. Once group assignment was made based on outcome, a variety of psychologic, socioeconomic, and demographic data obtained at the time of program admission was analyzed to determine if there were differences among the groups. Several factors were found to distinguish among the groups, including Minnesota Multiphasic Personality Inventory (MMPI) and Millon Behavioral Health Inventory (MBHI) scale scores, prior surgical history, level of worker compensation, and pain intensity ratings. These results confirm the presence of psychosocioeconomic differences among CLBP patients and suggest the need for continued research in this area to improve treatment efficacy in these patients.
Adult↗
A psychosociomedical prediction model of response to treatment by chronically disabled workers with low-back pain.
There has been much interest in identifying variables that can predict which individuals are susceptible to developing chronic low-back pain. There currently are a number of studies that are evaluating primary predictors (which uninjured workers are likely to develop chronic low-back pain) and secondary predictors (which workers with acute episodes will develop chronic pain). The present study reports the first results from a large-scale investigation of tertiary predictors. Specifically, it addresses the issue of what psychosociomedical variables are predictive of success/failure in response to a comprehensive Functional Restoration treatment program by workers who are chronically disabled with low-back pain. Three stages were involved in the development of this prediction model. First, a group of treatment and research professionals who had extensive experience in the area of chronic low-back pain identified an array of 42 variables, from a larger pool of quantified physical, psychosocial, and medical parameters rated to be important with this patient population.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Abnormal signal in deep white-matter infarction.
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Brain↗