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Biomedical subjects

M Stephens

Publications and source records attributed to M Stephens.

At least 19 recordsLinked to original sources
PubMed2000

Association mapping in structured populations.

The use, in association studies, of the forthcoming dense genomewide collection of single-nucleotide polymorphisms (SNPs) has been heralded as a potential breakthrough in the study of the genetic basis of common complex disorders. A serious problem with association mapping is that population structure can lead to spurious associations between a candidate marker and a phenotype. One common solution has been to abandon case-control studies in favor of family-based tests of association, such as the transmission/disequilibrium test (TDT), but this comes at a considerable cost in the need to collect DNA from close relatives of affected individuals. In this article we describe a novel, statistically valid, method for case-control association studies in structured populations. Our method uses a set of unlinked genetic markers to infer details of population structure, and to estimate the ancestry of sampled individuals, before using this information to test for associations within subpopulations. It provides power comparable with the TDT in many settings and may substantially outperform it if there are conflicting associations in different subpopulations.

Alleles↗
PubMed1992

Cheilectomy for hallux rigidus.

Cheilectomy is the excision of an irregular osseous rim that interferes with joint motion. Twenty cases of hallux rigidus/limitus treated by cheilectomy have been reviewed 18 months after surgery. A satisfactory outcome was achieved in all but 2 cases, which were failures. Range of joint motion, in particular dorsi flexion, improved in all but 6 cases. Cheilectomy is a simple and effective alternative to arthrodesis in the treatment of hallux rigidus.

Adult↗
PubMed1992

Combined high grade sarcoma and serous ovarian neoplasm.

A case of an ovarian serous epithelial neoplasm of borderline type admixed with sarcomatous elements is reported. This combination seems to be extremely rare with only four cases previously reported. It may represent a type of collision tumour or the development of a sarcoma in a growth with borderline differentiation.

Adenofibroma↗
PubMed1992

Human articular surface chondrocytes initiate alkaline phosphatase and type X collagen synthesis in suspension culture.

The type X collagen is a short chain collagen associated with calcific cartilage and/or the expression of the hypertrophic chondrocyte phenotype. In articular cartilage, type X collagen is restricted to the basal zone of calcified cartilage adjacent to the subchondral bone. However, during pathological change such as in osteoarthritis, the synthesis of type X collagen becomes more widespread but never extends to the articular surface. Using immunocytochemistry and fluorography of newly synthesised collagens, we report that surface articular chondrocytes (which occupy the uppermost 10-15% of the tissue depth) from normal human cartilage initiate de novo synthesis of both type X collagen and alkaline phosphatase when maintained in suspension culture.

Alkaline Phosphatase↗
PubMed1991

Fibre distribution in the lungs and pleura of subjects with asbestos related diffuse pleural fibrosis.

The lungs from 13 cases of diffuse pleural fibrosis associated with a history of exposure to asbestos were examined. Samples were taken from the visceral pleura and central and subpleural zones of the lungs for histopathological and mineralogical studies. The fibre type, size, and number were estimated for each of these regions by transmission electron microscopy and energy dispersive x ray analysis. Amphibole fibre counts were raised when compared with a non-occupationally exposed group and matched those seen in cases of pleural plaques, mild asbestosis, and mesothelioma. A wide case to case variation of distribution was seen. No significant difference was apparent between central and subpleural zones, whereas low asbestos counts were found in the pleura; these were mainly short chrysotile fibres. Within the lungs more (45%) of the longer (greater than 4 microns) and thinner (less than 0.25 micron) amphibole fibres were retained in keeping with other studies implicating such fibre profiles in the pathogenesis of asbestos related disease.

Aged↗
PubMed1991

A computer-assisted health care cost management system.

To our knowledge, First Chicago has developed and implemented the first operational integrated health data computer system that includes the traditional occupational medicine data base together with medical claims and health risk appraisal data. OMNIS has combined medical claims, personnel, disability, employee assistance program, wellness program participation, administrative functions, laboratory, periodic health evaluation data, and health risk appraisal data in a single system. OMNIS provides data that are being used to more accurately predict health care and disability costs and design intervention strategies. Clearly, the integrated health data computer system provides information to manage increasingly complex issues of health care quality and cost. For companies concerned about the quality as well as the cost of health care, an integrated health data computer system (OMNIS) may be a valuable tool to objectively assess quality of care. For example, a company could evaluate how effectively various providers (eg, health maintenance organizations, preferred provider organizations, indemnity plan) control medical conditions such as hypertension. Integrated health data management systems have the potential to assist in the selection of the highest quality and most cost-effective health care plans.

Chicago↗
PubMed1989

Relationship of cytosolic ion fluxes and protein kinase C activation to platelet-derived growth factor induced competence and growth in BALB/c-3T3 cells.

Platelet-derived growth factor (PDGF) and other agents that activate protein kinase C (PKC) rapidly alter cytosolic pH (pHi) and intracellular free calcium ([Ca++]i) in BALB/c-3T3 fibroblasts. To define whether changes in pHi or [Ca++]i are linked to PDGF-stimulated mitogenesis, these parameters were assessed in control and PKC depleted fibroblasts. PDGF addition to BALB/c-3T3 fibroblasts resulted in transient acidification of the cytoplasm followed by prolonged cytosolic alkalinization. Exposure of cells to 12-tetradecanoylphorbol-13-acetate (TPA), a phorbol ester that activates PKC, resulted in cytosolic alkalinization without prior acidification. Overnight incubation with 600 nM TPA decreased the total cell PKC histone phosphorylating activity in BALB/c-3T3 fibroblasts by greater than 90%. In PKC-deficient fibroblasts, TPA, and PDGF-induced alkalinization was abolished. In addition, the transient drop in pHi seen initially in control cells treated with PDGF is sustained to the point where pHi is fully 0.6-0.7 pH units below control cell values for up to 30 minutes. PDGF increased [Ca++]i threefold; this transient rise in [Ca++]i was only minimally affected (less than 15%) by lowering of the extracellular calcium level with ethylene glycol bis(b-aminoethyl ether)0 N,N,N' tetraacetic acid (EGTA) or blocking calcium influx with CoCl2. In contrast, 8-(diethylamine)-octyl-3,4,5-trimethoxybenzoate (TMB-8), an agent thought to inhibit calcium release from intracellular stores, substantially inhibited the rise in [Ca++]i caused by PDGF. TPA and 1-oleoyl-2-acetylglycerol (OAG) increased [Ca++]i but in contrast to PDGF this effect was blocked by pretreatment of cells with EGTA or CoCl2. In PKC-deficient fibroblasts, PDGF still increased [Ca++]i and stimulated DNA synthesis as effectively as in controls. TPA and OAG however, no longer increased [Ca++]i. The continued ability of PDGF to stimulate DNA synthesis in the face of sustained acidification and the absence of PKC activity suggests that cytosolic alkalinization and PKC activation are not essential for PDGF-induced competence in BALB/c-3T3 fibroblasts.

Animals↗
PubMed1989

Radiosensitizing and cytotoxic effects of nitroimidazoles in CHO cells expressing elevated levels of glutathione-S-transferase.

A cell line, CHO-Chlr, which has elevated levels of glutathione-S-transferase (GST), is resistant to damage caused by bi-functional nitrogen mustards. This cell line has a similar radiation sensitivity to and value of oxygen enhancement ratio as the wild type cells, CHO-K1, from which the mutant line was derived. Hypoxic cell radiosensitizing efficiencies for misonidazole, etanidazole (SR2508), and pimonidazole (R0 03-8799) are similar in both cell lines with values for C1.6 of 0.5, 0.75, and 0.08 mmol dm-3 for each drug respectively. In contrast, for RSU 1069 the sensitizing efficiency is lower in the cell line showing elevated levels of GST. The hypoxic toxicity of RSU 1069 and misonidazole is similar in each cell line, whereas in air, toxicity is 2 fold less in the CHO-Chlr cells. These results suggest that reaction of the alkylating aziridine part of RSU 1069 contributes to the high sensitizing efficiency of this drug. This is likely to be a consequence of either binding of the sensitizing moiety at the target site (ie, increased local concentration or induction of sub-lethal damage that is only expressed on subsequent irradiation.

Animals↗
PubMed1989

Journal of Manipulative & Physiological Therapeutics: a bibliographic analysis.

The first 9 years of the Journal of Manipulative and Physiological Therapeutics (JMPT) (1978-1986) were surveyed to determine concentrations of research activity, educational backgrounds of contributors, sources of funding for chiropractic science, and the volume and kinds of research in chiropractic. Most articles were authored by chiropractors but a fourth of all articles included contributors with scientific/academic doctorates. Most chiropractors were affiliated with a chiropractic college, but collaboration among chiropractic colleges was rare. A recent increase in contributions from private practitioners was also evident. Authors with medical training were uncommon (6%). National College and Canadian Memorial together accounted for 43% of all articles, and 72% of papers whose authors gave chiropractic college affiliations. Authors acknowledged 30 funding sources, and the Foundation for Chiropractic Education and Research (FCER) accounted for a third of all grants (18 of 55). Empirical studies increased in frequency from 1978 to 1986, but accounted for less than half of the papers. Case reports have been the most common form of original data report; 39 were published in JMPT during the 9 year period. Controlled clinical trials of chiropractic healing methods were extremely rare (3 of 334 papers). A need for greatly expanded clinical research in chiropractic is suggested.

Abstracting and Indexing↗
PubMed1988

An assessment of a double-isotope method for the detection of transferrin accumulation in the lungs of patients with widespread pulmonary infiltrates.

1. The accumulation in the lung of the plasma protein transferrin was determined in 44 patients with widespread pulmonary infiltrates of various causes and in 11 healthy volunteers using a double-isotope method based on labelling in vivo of circulating transferrin with indium and erythrocytes with technetium. 2. In 22 patients meeting criteria for the adult respiratory distress syndrome (ARDS) the mean transferrin accumulation rate was threefold greater (P less than 0.005) than in 22 patients not meeting these criteria, although most possessed an appropriate risk factor for ARDS, in addition to extensive radiographic changes. 3. The double-isotope method did not completely separate patients with ARDS from those not meeting the criteria or from control subjects and cannot be considered a diagnostic test for the condition. Statistically significant rates of transferrin accumulation, however, occurred more frequently in patients with ARDS (82%) than in controls (64%) or in those without ARDS (59%).

Adolescent↗