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J Cooke

Publications and source records attributed to J Cooke.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro.

This study tested the effects of fluid-induced shear on high density monolayer cultures of adult articular chondrocytes. Fluid-induced shear (1.6 Pa) was applied by cone viscometer to normal human and bovine articular chondrocytes for periods of 24, 48, and 72 hours. At 48 and 72 hours, fluid-induced shear caused individual chondrocytes to elongate and align tangential to the direction of cone rotation. Fluid-induced shear stimulated glycosaminoglycan synthesis by 2-fold (p < 0.05) and increased the length of newly synthesized chains in human and bovine chondrocytes. In human chondrocytes, the hydrodynamic size of newly synthesized proteoglycans also was increased. After 48 hours of fluid-induced shear, the release of prostaglandin E2 from the chondrocytes was increased 10 to 20-fold. In human chondrocytes, mRNA signal levels for tissue inhibitor of metalloproteinase increased 9-fold in response to shear compared with the controls. In contrast, mRNA signal levels for the neutral metalloproteinases, collagenase, stromelysin, and 72 kD gelatinase, did not show such major changes. This study demonstrated that articular chondrocyte metabolism responds directly to physical stimulation in vitro and suggests that mechanical loading may directly influence cartilage homeostasis in vivo.

Aged↗
PubMed1995

The chick Brachyury gene: developmental expression pattern and response to axial induction by localized activin.

The mouse Brachyury gene (T) is required in notochord differentiation and posterior mesoderm formation during axial development. We have isolated the chick homologue of T(Ch-T) and determined its putative protein sequence and expression pattern during embryogenesis. Ch-T is expressed in the epiblast close to and within the primitive streak, in early migrating mesoderm and in the notochord. In later stages Ch-T expression is found in the tail bud and in the entire notochord. The notochord expression ceases in an anterior-posterior wave when the formation of the body anlage is completed. This pattern is consistent with those reported for the expression of the mouse T gene and the T homologues of Xenopus laevis and zebrafish, suggesting that the mechanisms of embryonic pattern formation are highly conserved in all vertebrates. The N-terminal half of Ch-T shows a very high degree of sequence identity with the corresponding region of mouse T which has DNA-binding activity, and with the N-terminal half of Xenopus (Xbra) and zebrafish (Ntl) T protein. Finally, we have analyzed the effects of activin A on Ch-T induction and axis formation. Localized activin A treatment of prestreak blastoderms results in ectopic Ch-T expression that correlates with formation of second primitive streaks or with repositioning of the site of single streak origin (Cooke et al., 1994). These results strengthen the previous evidence that Brachyury activation is an early response to axis-inducing signals in vivo.

Activins↗
PubMed1994

Age-accumulation of fluoride in an experimental population of short-tailed field voles (Microtus agrestis L.).

This paper reports on the effects of a diet of vegetation contaminated by atmospheric fluorides upon the growth and age-accumulation of fluoride by a laboratory-maintained population of the short-tailed field vole, M. agrestis, a wild herbivore. Offspring of the voles fed the contaminated diet generally had lower growth rates and body weights during infancy and early adulthood than those fed a reference diet. The concentration and total fluoride burden of the femur were significantly higher in voles fed the contaminated diet. Following birth, the incisors of all offspring appeared normal, regardless of diet. Later, from approaching weaning onwards, the incisors of offspring weaned on to the contaminated diet showed marked morphological changes and severe dental lesions. Fluoride concentrations in the femur increased rapidly in late-suckling infants whose mothers were fed the contaminated diet, but appeared to reach an equilibrium concentration in adults which coincided with a slowing of the growth rate. Age is clearly an important influence upon the toxicology of fluoride because it affects the rate of accumulation by skeletal tissue.

Age Factors↗
PubMed1994

Control of cell behavior during vertebrate development by Slug, a zinc finger gene.

Slug, a vertebrate gene encoding a zinc finger protein of the Snail family, is expressed in the neural crest and in mesodermal cells emigrating from the primitive streak. Early chick embryos were incubated with antisense oligonucleotides to chick Slug. These oligonucleotides specifically inhibit the normal change in cell behavior that occurs at the two sites in the emerging body plan in which the gene is expressed. This change, which is the transition from epithelial to mesenchymal character, occurs at the formation of mesoderm during gastrulation and on emigration of the neutral crest from the neural tube.

Amino Acid Sequence↗
PubMed1994

Interstitial laser photocoagulation as a treatment for breast cancer.

This preliminary report describes the use of interstitial laser photocoagulation to manage small breast cancers. Forty-four patients were treated with a diode laser of 805 nm under local anaesthesia in the interval between diagnosis and surgery. Ultrasonography was used in 42 patients and computed tomography (CT) in two to place the fibre in the tumour and monitor laser effects. Laser-induced necrosis within the resected tumour varied from 0 to 25 mm in diameter. The presence of charring in the tumour around the fibre tip after treatment was associated with significantly larger diameters of necrosis than when charring did not occur (median 13 versus 6 mm, P = 0.002). Precharring the fibre resulted in a more predictable diameter of necrosis (median 14 mm). Ultrasonography was inaccurate in assessing laser damage; dynamic CT and magnetic resonance imaging may be of more use. Interstitial laser photocoagulation is simple and safe, and can produce necrosis of a reasonably predictable extent.

Breast↗
PubMed1994

Experimental control of axial pattern in the chick blastoderm by local expression of Wnt and activin: the role of HNK-1 positive cells.

Small grafts from transfected mammalian cell lines that secrete activin or express Wnt-1 RNA were made to the marginal zone of entire chick blastoderms in culture. Grafts from appropriate control cell lines produced no effects on development. The activin-secreting grafts, implanted before streak formation, could cause the streak to form opposite their marginal position even when this was 180 degrees distant around the blastoderm from the original presumptive streak site. Alternatively, opposed twin streaks were observed, one at the original presumptive site and one in relation to the graft. Wnt-expressing grafts implanted early could also reposition axis formation, but only to graft sites within approximately 100 degrees of angular distance from the host's presumptive streak origin. No Wnt-induced twinning was observed. Grafts of both experimental cell types intermixed were the most effective in reorientating, twinning, or globally disturbing the axial pattern and led to second axes with the least delay, relative to normal development, in reaching headfold stages. The incidence and distribution of cells positive for the epitope HNK-1 was investigated during early stages of normal and of experimentally twinned development. Only two nonhypoblast regions of HNK-1 expression were consistently observed in normal early development; a sector in the germ wall area opaca, behind the site of streak formation, and then a localised region of intensely, newly expressing cells arising in epiblast and in anteriormost parts of the (epiblast-derived) streak at the half-length streak stage. Both "activin only" and "activin/Wnt" mixed grafts, although not control grafts, became surrounded by new sectors of "germ wall" HNK-1 positivity. Such positivity may therefore mark a cell group with a signaling role (but no anatomical participation) in streak initiation. However, there was no change of the local background incidence of epiblastic HNK-1 positivity in the structure of streaks induced by "activin only" grafts. This indicates that most cells of the streak are specified by relatively local induction, rather than deriving from selective aggregation. Only grafts including the Wnt-expressing cells gave rise to obvious new HNK-1 expression within epiblast-derived cells anteriorly, as does the complete normal streak. This suggests that the Wnt class of response pathway can complement the activin one in producing rostrocaudally complete axial pattern, as has been suggested for amphibian development.

Activins↗
PubMed1994

Gradual selection of a cellular clone presenting a mutation at codon 179 of the p53 gene during establishment of the immortalized human breast epithelial cell line HMT-3522.

We studied the occurrence of a p53 mutation along passages stored as frozen vials during establishment of a nontumorigenic human mammary epithelial cell line HMT-3522. Mutations were identified by a PCR-SSCP approach using DNA as a template. The mutation, a nonconservative nucleotide substitution at codon 179 changing a histidine into an asparagine, appeared between passages 51 and 63 and was concommitant to a change in growth conditions. Cells were no longer grown on collagen coat and cell growth was not responsive to insulin, transferrin, or hydrocortisone anymore. To assess if the mutation was an early or a late event during cell line evolution we put a vial of cells frozen at passage 30 back into culture and tested for the appearance of a p53 mutation along newly produced passages. The same mutation (His to Asp at codon 179), as previously identified, reemerged between passages 48 and 52, thus indicating that the mutation was preexisting in passage 30 and gradually selected out because of the growth advantage it conferred. In order to gain in sensitivity we used a RFLP approach on PCR fragments which allowed us to detect the mutation as early as passage 44. Hence it took 14 passages (approx 50 cell doublings) for the mutated cells to become detectable and another 9 passages (33 generations) to overgrow the wild-type component of the population. We calculated that the mutated cells acquired a growth advantage which allowed them to cycle 1.2 +/- 0.05 faster than wild type. Computer simulations were consistent with the mutation appearing at passage 20.

Breast↗
PubMed1994

Ductal carcinoma in situ presenting as a stellate lesion on mammography.

Ductal carcinoma in situ (DCIS) usually manifests as microcalcification on mammography, but several other unusual forms of presentation on mammography are also described. One such atypical appearance is the stellate mass without calcification. This may occur with DCIS alone or when DCIS is associated with a complex sclerosing lesion (CSL). We retrospectively analysed the histopathological specimens and mammograms of women who were referred for biopsy from two large breast screening programmes, and were found to have DCIS as the dominant histological lesion. Of 677 women referred for surgical biopsy, 86 (13%) showed histological evidence of DCIS as the predominant lesion, and of these, seven (8%) showed a stellate appearance on mammography without associated calcification. In three cases the mammographic appearance was due to DCIS alone, and four were due to a CSL with associated DCIS. Only one case showed microinvasion (< 1 mm), and this was not large enough to account for the stellate lesion. We advocate biopsy of all radial lesions which are not surgical scars, as malignancy associated with benign lesions such as CSLs could be missed by cytological sampling errors.

Aged↗
PubMed1994

Using cost-effectiveness analysis for formulary decision making: from theory into practice.

The growth of expenditures on healthcare and pharmaceutical products is a concern to third-party payers because of the absence of market discipline (price signals that consumers face). Cost-effectiveness analysis is a method that allows third-party payers to systematically make judgements about the 'value for money' of these products. It moves beyond simple unit price comparisons of alternate interventions/products to consider the full stream of relevant cost and benefits. As formulary committees begin to adopt the systematic use of cost-effectiveness analyses to inform the debate, the exercise will move from an academic to a more practical application. This transition will require several important changes including defining the purpose of cost-effectiveness analysis, measurement of outcomes and data, format of reports, and contractual arrangements between the pharmaceutical industry and analysts. As more 'real world' experience is gained in the practical application of cost-effectiveness analysis, the quality of data will improve as will its value as an aid to decision making.

Cost-Benefit Analysis↗
PubMed1994

A clearing in the crowd: innovations in emergency services.

Emergency department overcrowding may not be so much a result of inappropriate use of the emergency department as it is a problem of the unavailability and inaccessibility of primary care services in the community. The prevailing theory that people use the emergency department because they cannot afford care elsewhere does not hold true. The vast majority of patients surveyed as part of the Emergency Services Initiative had some type of coverage, primarily Medicare or Medicaid. Without additional primary care capacity to accommodate walk-in patients and to make appointments available within one to two weeks, emergency departments will remain over-crowded. In addition to increasing primary care capacity, services must be structured to be as convenient and amenable to patient use as the emergency department. The findings of the Emergency Services Initiative supports the Preferred Primary Care Provider guidelines for the assignment of a primary practitioner or team to each patient, 24-hour telephone access for medical advice, evening and weekend hours, accommodation of walk-in patients, and the provision of nonurgent appointments within a maximum of two to four weeks. In addition, easy access to ancillary services for lab tests and X rays is beneficial for attracting patients. Patient education is also necessary. Questioning by counselors indicated that patients often do not understand that primary care settings are more appropriate than the emergency department for treatment of minor health problems. The most effective way to implement change in the health care system may not be through broad, generic prescriptions but through well-designed programs tailored to specific sites and communities. Changing staff behavior is often as challenging as changing patient behavior. Pre-project planning and communication about purpose, scope, and procedures are necessary if projects are to begin and continue smoothly. Ongoing evaluation is also key.

Community-Institutional Relations↗
PubMed1993

Comparative clinical, microbiologic, and economic audit of the use of oral ciprofloxacin and parenteral antimicrobials.

OBJECTIVE: To examine the use of oral ciprofloxacin and parenteral antimicrobials in the treatment of acute infection (respiratory tract, urinary tract, blood) in hospitalized patients, with particular reference to severity of infection, outcome, and associated economic implications of each treatment. DESIGN: A prospective, multicenter comparative audit was conducted in the UK over an 18-month period. The audit was undertaken by clinical pharmacists who reviewed the antimicrobial treatment of patients with infective episodes, who were receiving or could have received oral therapy. PARTICIPANTS: Clinical pharmacists who collated the data all are employed in teaching hospitals. MAIN OUTCOME MEASURES: Patients were identified for analysis by their type of infection, severity of illness, antimicrobial prescribed, route of administration, and response to therapy. Additionally, data on costs of the antimicrobials prescribed and the supplementary costs of drug administration were calculated. RESULTS: Four hundred eighty-five patients were enrolled for analysis; 208 of the patients had respiratory tract infection, 112 had urinary tract infection, 138 had septicemia, and 27 had mixed infections. Sepsis scores were applied to 152 patients receiving oral ciprofloxacin and 333 patients receiving parenteral antimicrobials and yielded mean scores of 5.9 (SD 3.1, range 1-13) and 8.7 (SD 4.2, range 1-22), respectively. Of 485 patients, 188 were paired according to sepsis score results and route of administration. Resolution occurred in 133 patients (79 receiving oral and 54 receiving parenteral therapy), further therapy was required in 49 (11 oral and 38 parenteral), and treatment was withdrawn in 6 (4 oral and 2 parenteral). Microbiologic assessment yielded positive results in 227 patients (47 percent). Drug acquisition costs (based on 1 UK pound = 1.80 US $) per course of treatment were $47.23 (SD $38.32, range 5.40-218.70) for the oral group and $173.70 (SD 209.77, range 2.11-1021.40) for the parenteral group. Overall costs for treatment courses were $74.00 (SD $52.81, range 8.10-309.17) and $305.59 (SD $304.70, range 14.69-1345.00) for the two groups, respectively (p < 0.001). CONCLUSIONS: This study suggest that, in patients with moderate infective episodes, oral ciprofloxacin may reduce overall treatment costs compared with the use of parenteral antimicrobial agents.

Adolescent↗