Search PubMed⌕ Search

Biomedical subjects

M D West

Publications and source records attributed to M D West.

27 records · Page 2Linked to original sources

Return to work for persons with traumatic brain injury: a supported employment approach.

Supported employment was used to place 41 persons into competitive employment during 30 months. All individuals had experienced severe head injuries; almost 70% of injuries were due to motor vehicle accidents. A mean of seven years had passed since injury for all referred clients, who had been unconscious a mean of 53 days. Only 36% of referred clients had achieved any competitive postinjury employment, compared with 91% of the same group who were competitively employed before injury. A job retention rate of 71% was reported, with most jobs in warehouse, clerical, and service-related occupations. A mean of 291 hours of job coaching was required to place and maintain all clients in supported employment.

Adolescent↗

Replicative senescence of human skin fibroblasts correlates with a loss of regulation and overexpression of collagenase activity.

The atrophy of extracellular matrix is a common event during the aging of connective tissues. In this study, we tested the hypothesis that the altered ability of senescent cells to be modulated by serum growth factors correlated with a loss of regulation of collagenase synthesis. We examined the levels of immunoreactive procollagenase and collagenase inhibitor (the tissue inhibitor of metalloproteinases, TIMP) associated with young and senescent fibroblasts cultured in vitro. Young fibroblasts cultured in low (0.5%) concentrations of fetal bovine serum respond to increased (10%) serum by increasing levels of procollagenase and TIMP beginning 4.0 h after serum stimulation. In contrast, senescent fibroblasts constitutively produce relatively high levels of procollagenase even when cultured in low levels of serum and do not respond to serum stimulation by increasing procollagenase synthesis. In addition, senescent fibroblasts constitutively express a relatively small amount of TIMP which is not induced upon serum stimulation. This altered expression of collagenase and TIMP appears unique to the senescent phenotype and not merely a result of growth inhibition, since young cells growth arrested by density-dependent growth inhibition displayed a temporal pattern of procollagenase and TIMP expression upon serum stimulation similar to that of subconfluent young cultures. An assay of net collagenase activity revealed a greater than 20-fold elevation of activity in trypsin-activated extracts from senescent versus young fibroblasts when cultured in a low concentration of fetal bovine serum. These results demonstrate for the first time a direct correlation between alterations in the molecular pathways regulating connective tissue homeostasis and those of replicative senescence. The increased collagenolytic activity of senescent compared to young fibroblasts cultured in the presence of a low serum concentration suggests that aging fibroblasts may become increasingly fibroclastic causing many of the age-associated alterations in dermal collagen observed during aging in vivo.

Blotting, Western↗

Characterization of the serological cross-reactivity between glycoproteins of the human immunodeficiency virus and equine infectious anaemia virus.

The reported serological relatedness between the major glycoproteins of human immunodeficiency virus (HIV gp120) and equine infectious anaemia virus (EIAV gp90) was examined using purified antigens in radioimmunoprecipitation (RIP), radioimmunoassay (RIA) and immunoblot assays with reference serum from acquired immunodeficiency syndrome (AIDS) patients, an anti-gp120 goat serum and EIAV-infected horse serum. To assess the contributions of glycoprotein oligosaccharide and peptide components to any observed reactivities, antigens treated with endoglycosidase F to remove carbohydrate were assayed in parallel with the intact glycoprotein. The results of the experiments indicated that the reactivity observed for each antigen was dependent on the immunoassay employed. The RIP and RIA analyses demonstrated that HIV gp120 is equally reactive with the AIDS patient serum, the goat anti-gp120 serum and the EIAV-infected horse serum, whereas the EIAV gp90 reacted only with the horse serum. In immunoblot assays, the HIV gp120 reacted with AIDS patient serum, but not with the EIAV-infected horse serum. Deglycosylation of the HIV gp120 evidently increased its reactivity with the AIDS patient serum, had no significant effect on its reactivity with the goat antiserum, and essentially abolished its reactivity with the EIAV reference serum. Thus, it appears that the serological cross-reactivity observed between HIV gp120 and sera from EIAV-infected horses can be attributed to the oligosaccharide rather than the peptide components of the viral glycoprotein. These studies also emphasize the necessity of employing several assay procedures in assessing lentivirus antigenicity.

Acquired Immunodeficiency Syndrome↗

Preparative elution of proteins from nitrocellulose membranes after separation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

Various conditions were analyzed and optimized for the preparative elution of proteins from nitrocellulose membranes after transfer from sodium dodecyl sulfate (SDS)-polyacrylamide gels. The efficiency of elution was best using pyridine or acetonitrile elution solvents, intermediate for buffer containing a mixture of sodium dodecyl sulfate, Triton X-100, and sodium deoxycholate, and negligible for buffers containing any single detergent or chaotropic salt, such as urea or guanidine hydrochloride. The efficiency of elution with any solvent also depended on the molecular weight of the proteins, smaller proteins being more easily removed from membranes. As a general procedure, proteins may be eluted from nitrocellulose membranes by incubation with either 40% acetonitrile or 50% pyridine in 0.1 M ammonium acetate, pH 8.9, for 1-3 h at 5-37 degrees C. The recommended procedures for protein elution appear to offer a rapid, simple, and efficient means of recovering proteins from complex mixtures after separation by SDS-PAGE and transfer to nitrocellulose membranes.

Acetonitriles↗

An assessment of the potential use of anionic dextrans as a plasma substitute.

Several problems exist when dextrans are used as plasma substitutes. High molecular weight dextrans can cause red cell aggregation and increased blood viscosity. Low molecular weight dextrans, although shown to improve circulation and promote flow, are removed rather rapidly from the circulation due to high premeation rates across capillary walls. In the present study, a small anionic charge is introduced onto the dextran to make it electrostatically negative. Since capillary walls have been shown to retain negatively charged solutes in preference to neutral solutes, the anionic dextran should retain its effectiveness for longer periods of time compared to similar sized neutral dextran. Studies were done on eight unanaesthetized dogs to compare the relative disappearance rates of dextran and anionic dextran (carboxymethyl dextran) from the circulation. It was shown that anionic dextrans do remain in the circulation over a longer period of time compared to neutral dextrans.

Animals↗

Re-expression of senescent markers in deinduced reversibly immortalized cells.

We have developed a simian virus 40 (SV40) T-antigen immortalized human cell line, 1MR90-D305.2H4 (IDH4), in which the expression of T-antigen is controlled by the mouse mammary tumor virus (MMTV) promoter and thus regulated by steroids such as dexamethasone. Studies on the regulation of proliferation by T-antigen led to the formulation of a two-stage model for human cell immortalization, in which a mortality stage 1 mechanism (M1) was the target of T-antigen action, and an independent mortality stage 2 mechanism (M2) produced crisis and prevented T-antigen from directly immortalizing cells. Rarely, a cell expressing T-antigen escaped crisis (e.g., M2) and was capable of indefinite proliferation. This model predicted that the deinduction of T-antigen in IDH4 cells would lead to the reexpression of the M1 mechanism, and thus a reexpression of the senescent phenotype. Our study confirms the prediction that, in the absence of steroids, IDH4 cells express a variety of morphological and biochemical markers characteristic of normal senescent human fibroblasts.

Antigens, Viral, Tumor↗

Altered expression of plasminogen activator and plasminogen activator inhibitor during cellular senescence.

Fibroblast senescence is associated with a loss of proliferative potential and an alteration in extracellular gene expression. Because the expression of extracellular gene products are frequently growth state dependent, we undertook a comparative study of the regulation of the components of the plasminogen activation system in young and senescent cells under controlled conditions of growth. Young and senescent cells were compared in quiescent and activated growth conditions for the secretion of tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2). Whereas young cells showed decreased levels of PAI-1 in the secreted and extracellular matrix pools upon serum deprivation, senescent cells showed a more constitutive pattern of gene expression, with no noticeable decrease of the levels in a low concentration of serum. RNA analysis revealed that senescent lung and skin cells, independent of the growth state, constitutively express levels of u-PA and PAI-1 comparable to the expression levels in young mitotically growing cells. These expression levels are down-regulated in quiescent young cells. In contrast, both t-PA and PAI-2 were markedly overexpressed in senescent skin lung cells under all growth conditions. Total plasminogen activator activity in conditioned medium was 50-fold higher in senescent-cell medium compared to young when cultured in 0.5% fetal calf serum (FCS) for five days, with the majority of the activity co-migrating on zymograms with u-PA. Increases in PAI-1 was also observed in senescent human umbilical vein endothelial cells. In summary, cells of various types display alterations in plasminogen activator activity during replicative senescence. The inappropriate over-expression of plasminogen activator activity in vivo may be expected to lead to a progressive disruption of extracellular matrix maintenance. Thus, our observations suggest that cellular replicative senescence is associated with an altered expression of several genes regulating tissue maintenance which, in turn, could lead to degenerative changes in tissue in age-related disease(s).

Base Sequence↗

The projected supply of registered nurses, 1990.

The number of employed registered nurses (RNs) in the United States stood at an all-time high of 1.3 million in 1980. This paper, using life table techniques, develops a population base of all living graduates from data on graduations from basic nursing education programs between 1928 and 1980, and estimates that there are some 1.9 million graduates now living. The number of graduates is projected to rise to some 2.4 million by the end of 1990, of whom 1.7 million will be active in the profession. Factors taken into account include recent increases in admissions, which rose from 79,000 in 1970 to 112,000 in 1980; the extent to which older women are entering the profession; the rapid growth of 2-year associate degree programs, which now account for half of all admissions; and increased labor force participation, with 68 percent of all living graduates in the labor force in 1980, compared to 60 percent in 1970. It is projected that the movement to advanced education among RNs will continue so that, by 1990, the proportion with baccalaureate or higher degrees will have risen from 29 to 36 percent of the employed RNs. By 1990 the largest number of active RNs will be in their 30s. Graduates with diplomas will have a median age of 45; those with associate degrees, 35; and those with baccalaureate or higher degrees, 32 years.

Adult↗