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Biomedical subjects

J Cooke

Publications and source records attributed to J Cooke.

At least 91 records · Page 5Linked to original sources
PubMed1993

Expression of the HNK-1 epitope is unaltered among early chick epiblast cells despite behavioral transformation by inducing factors in vitro.

Dissociated epiblast cells from pre-streak chick blastoderms have been exposed, in short-term culture on a fibronectin (FN) substratum, to recombinant mammalian activin and to mammalian basic fibroblast growth factor (bFGF). Such cultures have also been made on this substratum pre-conditioned by culture of a transfected cell line expressing the mammalian Wnt-1 gene. The former two factors induce changes of FN adhesiveness and other behavior, such that the cultures after 6 h resemble cultures newly set up from the young primitive streak or substreak hypoblast region of similarly aged blastoderms that have developed onward across the intervening period (see Cooke and Wong, Development 111: 197-212, 1991 for related results). Over 95% of cells are potentially responsive, and with relatively high concentration of activin there is also production of nodular structures due to strong cell-cell adhesion, as in cultures from Hensen's node or the anterior streak. Pre-conditioning of the substratum by transfected Wnt-1-expressing cells does not appear specifically to alter behavior in such epiblast cultures, though these experimental cells, and not control-transfected ones, produce striking alterations of chick development in other experiments (Cooke et al., in preparation). Up to 20% of cells in control cultures from central or 'marginal zone' pre-streak epiblast express the HNK-1 epitope, while up to 60% of cultured early streak cells cleaned of hypoblast do so.(ABSTRACT TRUNCATED AT 250 WORDS)

Activins↗
PubMed1992

The influence of an academic representative on prescribing by general practitioners.

1. The effect of providing information about medicines by a short 'sales' interview between individual general practitioners and an 'academic representative' on prescribing was investigated. 2. The promotional campaign was designed to encourage a rational approach to prescribing of non-steroidal anti-inflammatory agents in an intervention group of 101 general practitioners selected at random from the Leeds Family Practitioner Committee (FPC). The remaining general practitioners in the Leeds FPC acted as a reference group. 3. The prescribing data for each group for 5 months immediately prior to and 5 months following intervention were compared. 4. Intervention produced a significant increase (P less than 0.005) in the prescribing cost of ibuprofen, the non-steroidal promoted as first choice agent, which was sustained for at least 5 months. 5. Prescribing of the second choice agent, piroxicam, decreased in the reference group but not in the intervention group. 6. There was a decrease in the average prescribing cost of pounds 6.60 per doctor per month in the intervention group compared with the reference group.

Costs and Cost Analysis↗
PubMed1991

Effects of the steel gene product on mouse primordial germ cells in culture.

Mutations at the steel (sl) and dominant white spotting (W) loci in the mouse affect primordial germ cells (PGC), melanoblasts and haemopoietic stem cells. The W gene encodes a cell-surface receptor of the tyrosine kinase family, the proto-oncogene c-kit. In situ analysis has shown c-kit messenger RNA expression in PGC in the early genital ridges. The Sl gene encodes the ligand for this receptor, a peptide growth factor, called here stem cell factor (SCF). SCF mRNA is expressed in many regions of the early mouse embryo, including the areas of migration of these cell types. It is important now to identify the role of the Sl-W interaction in the development of these migratory embryonic stem cell populations. Using an in vitro assay system, we show that SCF increases both the overall numbers and colony sizes of migratory PGC isolated from wild-type mouse embryos, and cultured on irradiated feeder layers of STO cells (a mouse embryonic fibroblast line). In the absence of feeder cells, SCF causes a large increase in the initial survival and apparent motility of PGC in culture. But labelling with bromodeoxyuridine shows that SCF is not, by itself, a mitogen for PGC. SCF does not exert a chemotropic effect on PGC in in vitro assays. These results suggest that SCF in vivo is an essential requirement for PGC survival. This demonstrates the control of the early germ-line population by a specific trophic factor.

Animals↗
PubMed1991

A randomised study of the effects of osmolality and heparin with hydrocortisone on thrombophlebitis in peripheral intravenous nutrition.

Intravenous nutrition administered via the central route incurs both the risks of catheter insertion and catheter related sepsis. Peripheral intravenous nutrition avoids these risks but is associated with a high risk of thrombophlebitis. We undertook a study to look at the incidence of thrombophlebitis caused by the infusion of a) a 'ready to use' mixture (Vitrimix KV) with an osmolality of 1130 mOsmol/kg, b) Vitrimix KV plus heparin and hydrocortisone, and c) a feed, with an osmolality of 700 mOsmol/kg, with heparin and hydrocortisone, to investigate the effects of the addition of heparin and hydrocortisone and the effect of osmolality on the incidence of thrombophlebitis. The addition of heparin (500 u/l) and hydrocortisone (5 mg/l) to Feed A significantly reduced the daily risk of thrombophlebitis from 0.43 to 0.11 episodes per patient, p < 0.01. A reduction in the osmolality resulted in a further fall in the incidence of thrombophlebitis to 0.04 episodes per patient with a significant increase in the median life span of the cannula from 26 h to 86 h, p < 0.02. Our data show that a low incidence of thrombophlebitis can be achieved by the use of a low osmolality feed with heparin and hydrocortisone. It is recommended that peripheral intravenous nutrition be used in patients who require nutritional support for less than 10 days.

Journal Article↗
PubMed1991

Growth-factor-related proteins that are inducers in early amphibian development may mediate similar steps in amniote (bird) embryogenesis.

Xenopus and murine activin A homologues (XTC-MIF and WEHI-MIF) and Xenopus and bovine basic fibroblast growth factor (bFGFs) are potent inducers of mesodermal and endodermal pathways of development in amphibian blastular animal cap cells. Porcine transforming growth factor beta 2 (TGF beta 2) is a weaker inducer in the same assay but human platelet-derived growth factor (PDGF) is inactive. We have assayed these factors for evidence of homologous effects in bird development. Unlike amphibians, bird embryos never exhibit a clean segregation of a cell layer that has a uniform specification when uninduced, and can be cultured in isolation as an assay after exposure to soluble factors. We have therefore performed less direct experiments, of three types. We have briefly cultured early chick epiblast cells with and without factors and then assayed their capacity to attach and spread upon fibronectin, in comparison with young streak and substreak hypoblast cells. We have asked whether similar microculture with factors alters the ability of quail epiblast cells to disrupt morphogenesis, and to integrate into the structure, of host chick blastoderms into which they are seeded. Finally, whole early chick blastoderms have been preincubated with or without factors for a brief period before setting them up to develop in vitro under circumstances usually permitting successful formation of axial pattern. Strong effects of the activin-like factors, of bFGF and of TGF beta 2 were seen in all three procedures, while PDGF was essentially inactive. In epiblast cells, effective factors at picomolar concentrations induced stable spreading upon fibronectin, and a capacity to adhere and spread upon basal epiblast surface and prevent morphogenesis in host blastoderms. Preincubation of whole early blastoderms with these factors led to characteristic deviation from normal development over the subsequent 24 h. We therefore suggest that peptides from the particular families that are active as inducers in amphibian blastula ectoderm may mediate homologous or closely related steps in respecification throughout vertebrates.

Animals↗
PubMed1991

Use of cytogenetic methods to determine mutagenic changes in the blood of pharmacy personnel and nurses who handle cytotoxic agents.

Lymphocytes of subjects from throughout the United Kingdom were studied over a two-year period beginning in January 1985 to determine the level of chromosomal damage produced by environmental exposure to cytotoxic agents. A small pilot study was conducted to determine the expected background level of chromosomal aberrations. Four groups of subjects were then recruited: pharmacy personnel who reconstituted the drugs under recommended conditions, nurses who did not reconstitute the drugs but worked on units where patients received cytotoxic chemotherapy, unexposed office workers from the same geographic location as the pharmacy personnel and nurses (negative control), and patients receiving cytotoxic drugs (positive control). Subjects completed questionnaires about smoking, viral illnesses, radiation exposure, and medication use in the past 12 months; pharmacy personnel were asked the numbers of times (1) they had handled specific drugs and (2) spills had occurred with these drugs. Lymphocytes from subjects were incubated for 48 hours, and first-division metaphases were examined for chromosome and chromatid aberrations; damage was measured as the number of aberrations per 100 cells. For a blood sample to be included in the analysis, at least 100 metaphase divisions had to be examined. Data were analyzed for 50 pharmacy staff members, 11 nurses, 12 controls, and 6 patients. Metaphase divisions in cells of the pharmacy personnel and nurses indicated no significant difference in chromosomal damage compared with the unexposed office workers. When the pharmacy, nurse, and control groups were pooled into a nonpatient group and compared with the patient group, significantly greater damage was observed in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1990

Radiation-induced brachial plexus injury: follow-up of two different fractionation schedules.

All 449 breast cancer patients treated with post-operative radiotherapy to the breast and lymph nodes between 1982 and 1984 have been followed for 3-5.5 years. In this group two different fractionation schedules were used, one five times a fortnight and one daily, both over 6 weeks. The calculated dose to the brachial plexus was 45 Gy in 15 fractions or 54 Gy in 30 fractions. These schedules are equivalent doses using the standard NSD formula. The diagnosis of a brachial plexus injury was made clinically and computed tomography was used to distinguish radiation injury from recurrent disease. The actuarial incidence of a radiation-induced brachial plexus injury for the whole group was 4.9% at 5.5 years. No cases were seen in the first 10 months following radiotherapy. The incidence rises between 1 and 4 years and then starts to plateau. When the large fraction size group is compared with the small fraction size group the incidence at 5.5 years is 5.9% and 1.0%, respectively (p = 0.09). Two different treatment techniques were used in this group but were not found to contribute to the probability of developing a brachial plexus injury. It is suggested that radiation using large doses per fraction are less well tolerated by the brachial plexus than small doses per fraction; a commonly used fractionation schedule such as 45 Gy in 15 fractions may give unacceptably high brachial plexus morbidity; and the use of small doses per fraction or avoiding lymphatic irradiation is advocated.

Brachial Plexus↗
PubMed1990

CT scanning in patients following surgery on the tongue and floor of mouth.

Computed tomographic (CT) scanning was performed on 15 patients who had undergone carefully documented major surgery for malignancy to the tongue and floor of mouth in order to assess appearances of the face and neck following extensive resection. The appearances following a variety of operations, often with reconstruction, were identified. Familiarity with the normal post-operative anatomy allows the recognition of small volume recurrent tumour and the implementation of appropriate treatment.

Humans↗
PubMed1990

The biological effects of XTC-MIF: quantitative comparison with Xenopus bFGF.

Mesoderm in Xenopus and other amphibian embryos is induced by signals from the vegetal hemisphere acting on equatorial or animal hemisphere cells. These signals are diffusible and two classes of candidate signal molecule have been identified: the fibroblast growth factor (FGF) and transforming growth factor beta (TGF-beta) types. In this paper, we compare the effects of cloned Xenopus basic FGF (XbFGF) and electophoretically homogeneous XTC-MIF (a TGF-beta-like factor obtained from a Xenopus cell line) on animal pole explants. We find that they have a similar minimum active concentration (0.1-0.2 ng ml-1) but that, nonetheless, XTC-MIF is at least 40 times more active in inducing muscle. In general, we find that the two factors cause inductions of significantly different characters in terms of tissue type, morphology, gene expression and timing. At low concentrations (0.1-1.0 ng ml-1) both factors induce the differentiation of 'mesenchyme' and 'mesothelium' as well as blood-like cells. These latter cells do not, however, react with an antibody to Xenopus globin. This raised the possibility that the identification of red blood cells in other studies on mesoderm induction might have been mistaken, but combinations of animal pole regions with ventral vegetal pole regions confirmed that genuine erythrocytes are formed. The identity of the blood-like cells formed in response to the inducing factors remains unknown. At higher concentrations XTC-MIF induces neural tissue, notochord, pronephros and substantial and often segmented muscle. By contrast, XbFGF only induces significant amounts of muscle above 24 ng ml-1 and even then this is much less than that induced by XTC-MIF. For both factors an exposure of less than 30 min is effective. Competence of animal pole cells to respond to XbFGF is completely lost by the beginning of gastrulation (stage 10) while competence to XTC-MIF is detectable until somewhat later (stage 11). Since animal pole tissue is known to be able to respond to the natural inducer at least until stage 10, and perhaps until stage 10.5, this suggests that bFGF cannot be the sole inducer of mesoderm in vivo. Taken together, these results are consistent with XTC-MIF being a dorsoanterior inducer and XbFGF a ventroposterior inducer, suggesting that body pattern is established by the interaction of two types of inducing signal. This model is discussed in view of the qualitative and quantitative differences between the factors.

Animals↗
PubMed1989

A comparison of radiation doses to the breast in computed tomographic chest examinations for two scanning protocols.

Compared with other radiological examinations in which the breasts are directly exposed, the breast doses involved in computed tomographic (CT) chest examinations are high. A CT protocol which reduces such breast dose has been investigated. Breast doses have been measured for contiguous 10 mm scans and interspaced 3 mm scans. Differences in the breast doses were found between the left and right breasts for both scanning protocols. The dose associated with the interspaced scans was lower by a factor of about two compared with that for the contiguous scans.

Breast↗
PubMed1989

Normal CT anatomy of the tongue, floor of mouth and oropharynx.

A computed tomography (CT) technique is described which demonstrates the structures and tissue planes in the floor of mouth, tongue and oropharynx. The anatomy, which forms the basis for understanding pathological change, is given in detail and illustrated by axial and coronal images and line drawings.

Humans↗
PubMed1989

Computed tomographic scanning in patients with carcinoma of the tongue.

Computed tomographic (CT) scanning is useful for staging patients with carcinoma of the tongue. In a study of 13 patients scanned prior to treatment, CT gave additional valuable information about the primary tumour in four patients. Computed tomography detetected non-palpable, abnormal cervical lymph nodes in three patients which directly affected the nature of the subsequent operation.

Adult↗
PubMed1989

Gastrulation and larval pattern in Xenopus after blastocoelic injection of a Xenopus-derived inducing factor: experiments testing models for the normal organization of mesoderm.

When a Xenopus XTC cell-derived mesoderm-inducing factor (MIF) is injected into the blastocoel of Xenopus embryos before gastrulation, they develop almost normally until just after the onset of mesoderm involution at the internal blastoporal lip. Cells from the entire lining of the blastocoel roof and inner marginal zone then undergo a synchronous, sudden change of contact and arrangement which resembles the transformation undergone by normal mesoderm at its time of involution at the vegetal edge of the marginal zone. We describe a dose-dependent spectrum of subsequent abnormalities in gastrulation and, in cases where gastrulation partially recovers, in the resulting larval pattern. Because of such recovery, embryos injected with widely different doses may appear equally abnormal at the early gastrula stage but very different by control larval stages. Extra spinocaudal axial patterns, in the area of ectopic mesoderm, are seen after MIF doses that just permit recovery of gastrulation. The sudden cellular transformation corresponding to involution, in the ectopically specified mesoderm, spreads throughout the animal cap within 15 min in individuals, at a time significantly later than the earliest normal transformation in the marginal zone. No systematic alteration could, however, be detected in its timing, in relation to a 250-fold range of injected MIF concentration or a 3.5-hr difference in time of injection. The severity of the effects on final embryonic pattern is largely independent of the blastular stage of injections. Splitting of the total injected dose into two, separated by 2 to 3 hr of blastular development, reveals that the degree of effect on gastrulation and patterning depends only upon the highest experienced concentration at any time before response. When fibroblast growth factor (bFGF), a different effective mesoderm inducer, is similarly injected, a similar abnormal cell behavior and ectopic mesoderm formation are seen, but beginning only at midgastrular stages some 1.5 hr beyond that characteristic of XTC-MIF. The findings are introduced and discussed in terms of models for the natural organization of the time course of gastrulation and mesodermal pattern.

Animals↗