Search PubMed⌕ Search

Biomedical subjects

K Turner

Publications and source records attributed to K Turner.

At least 73 records · Page 4Linked to original sources

The positions of coronary arterial ostia.

The positions of the coronary arterial ostia were examined in the cadavers of 38 adults. All the ostia were related to the aorta and none to the pulmonary artery. The aortic valves in 37 specimens were normal and possessed three cusps, while one was bicuspid. In the normal specimens, the main right and left coronary ostia were confined to the anterior and left posterior aortic sinuses respectively, apart from one specimen in which the right ostium was related to the right posterior sinus. Six specimens had small accessory ostia, close to the main right ostium. The majority of ostia were situated on or immediately below the supravalvular ridge. Circumferentially, the ostia clustered near the maximum curvature of the sinus. In the single specimen where the aortic valve was bicuspid, both ostia lay more-or-less symmetrically in the sinus above an anterior cusp which showed evidence of formation from two components. The reasons for confinement of the coronary ostia two of the three aortic sinuses are not clear. Microscopic examination of serial sections through 22 human embryos of 5.0-17.5 mm CR length (Carnegie stages XIII-XIX) confirmed that the earliest vessels in the heart wall develop subepicardially near the apex at stage XV. The network extends centripetally and only at stage XVII could coronary arterial stems, communicating with the aortic lumen, be identified. The sequence suggests that confinement of the coronary ostia to the interior and left posterior sinuses probably occurs because these represent the most accessible contact points for the centripetally growing vascular plexus.

Adult↗

Leukemia inhibitory factor produces hypercalcemia in rats without altering bone histomorphometry of the tibia.

Leukemia inhibitory factor (LIF) is a single-chain polypeptide that previously was shown in mice to produce hypercalcemia and influence skeletal growth and turnover. We performed dose-response studies to determine if LIF alters the serum calcium or histomorphometry of the tibia in growing male rats. Forty animals were divided into five groups of eight animals each. Recombinant human LIF, 0.01, 0.1, 1, or 10 microg/100 g body wt, or vehicle was administered daily S.C. for 3 weeks. Compared with controls it was found that LIF increased mean serum calcium at the two highest doses (11.4 +/- 0.1 versus 10. 8 +/- 0.1 mg/dl, P = 0.0005 by one-way analysis of variance (ANOVA) but did not alter static or dynamic measurements of histomorphometry or length of the tibia. We conclude that in growing rats, high systemic concentrations of LIF result in hypercalcemia with no changes in bone turnover.

Animals↗

The influence of Vero cell culture on human embryo development and chorionic gonadotrophin production in vitro.

Co-culture of human embryos with cell layers has generally shown that blastocyst formation rates are improved compared to routine culture in medium alone. In order to assess this further, we have additionally classified resulting blastocysts according to their morphology and secretion of human chorionic gonadotrophin (HCG). A total of 70 supernumerary human embryos from 15 patients were divided equally and randomly between two culture conditions: (i) co-culture with Vero cells; and (ii) culture in our routine medium. Embryo development and morphology were recorded for up to 14 days in culture. The results showed that embryos on Vero cells had a significantly higher blastocyst formation rate (P < 0.02) by or on day 6 of development than those in routine culture medium alone (77 and 46% respectively). For HCG analysis, the culture medium was changed in both culture systems on days 5, 7, 9, 12 and 14 of embryo development and analysed. Most embryos began to produce HCG between days 7 and 9, with HCG secretion being significantly higher from embryos on Vero cells between days 9 and 12 than from embryos in routine culture (P < 0.03). The morphology of the blastocysts obtained was related to their ability to hatch and produce HCG but was not significantly better for one type of culture system than for the other.

Animals↗

Pharmacokinetic interactions between repeated dose phenylbutazone and gentamicin in the horse.

This study examined the pharmacokinetics of steady-state phenylbutazone and single bolus intravenous gentamicin when administered together in the horse. The trial design was completed as a cross-over with seven thoroughbred horses. In the first phase each horse received 2.2 mg/kg gentamicin intravenously. After a 2-week washout, each horse received 4.4 mg/kg phenylbutazone intravenously every 24 h for 5 days. On the fourth day each horse received gentamicin as before. Plasma was harvested for gentamicin concentration determination by fluorescence polarization immunoassay and for phenylbutazone concentration determination by high-performance liquid chromatography. All gentamicin data were best approximated by a two-compartment open model using sequential, weighted non-linear regression. Pharmacokinetic parameters were calculated using model-dependent formulae. Phenylbutazone data were analysed by non-compartmental methods. Phenylbutazone induced a 49% increase in the rate of gentamicin return to the central compartment from peripheral tissues (k21) (P < 0.05) and there was a trend to a 24% increase in k12 (P = 0.052). The gentamicin elimination half-life was decreased 23% and the Vd(urea) was reduced by 26%. No induction by gentamicin of changes in phenylbutazone pharmacokinetics were detected. In summary, phenylbutazone induced changes to the rate and extent of distribution and elimination of gentamicin. Therefore, care should be exercised in the use of aminoglycosides in equine patients concurrently maintained on phenylbutazone.

Animals↗

Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

Animals↗

Dual and triple therapy regimens of antisecretory agents and antibiotics for the eradication of Helicobacter pylori: an overview.

BACKGROUND: Studies evaluating therapeutic regimens that combine antisecretory agents with antibiotics for the eradication of H. pylori have reported significant variations in efficacy. METHODS: We reviewed the published literature to compare H. pylori eradication rates in patients treated with either omeprazole, ranitidine bismuth citrate (RBC), or ranitidine plus metronidazole combined with either amoxicillin or clarithromycin. RESULTS: Wide variations in H. pylori eradication rates have been reported with omeprazole plus either amoxicillin (0-100%) or clarithromycin (42-88%). Eradication rates ranging from 45% to 89% and from 74% to 94% have been reported with RBC plus either amoxicillin or clarithromycin, respectively. Eradication rates ranging from 48% to 90% have been reported with ranitidine plus metronidazole and amoxicillin and one study reported an eradication rate of 95% with ranitidine plus metronidazole and clarithromycin CONCLUSIONS: Well-controlled trials with ranitidine bismuth citrate plus clarithromycin suggest that this combination may provide the most consistent and effective regimen for the eradication of H. pylori infection.

Anti-Bacterial Agents↗

Interleukin-4 (IL-4) in combination with IL-11 or IL-6 reverses the inhibitory effect of IL-3 on early B lymphocyte development.

We have previously described a two-step methylcellulose culture system in which individual primitive progenitors from 5-fluorouracil (5-FU)-treated mice were shown to have both myeloid and B lymphoid differentiation capacity. Highly enriched Lin-Sca+FU2d BM cells were cultured in methylcellulose in the presence of Steel factor (SF), interleukin-7 (IL-7), and pokeweed mitogen stimulated spleen cell conditioned medium (PWM-SCM). Primary mixed myeloid colonies were replated after 8-11 days into secondary cultures containing SF and IL-7, which supported the generation of B220+sIgM- pre-B cell colonies. A number of growth factors, including IL-6, IL-11, granulocyte colony-stimulating factor (G-CSF), and IL-12 were shown to be capable of substituting for PWM-SCM to support the B lymphoid potential of primary colonies. B lymphoid potential was not supported, however, in SF + IL-3 or in SF + IL-3 plus any single growth factor (IL-1 to -12, granulocyte-macrophage colony-stimulating factor [GM-CSF], G-CSF, erythropoietin [Epo], leukemia inhibitory factor [LIF], tumor necrosis factor-alpha [TNF-alpha], transforming growth factor-beta [TGF-beta], gamma interferon [IFN-gamma], or insulin-like growth factor-1 [IGF-1]), but was supported in SF + IL-3 + 5% PWM-SCM. Experiments were designed to identify the factor or factors in PWM-SCM that reverse the inhibitory effects of IL-3 on B lymphoid potential. By substituting various cytokine combinations for PWM-SCM, we determined that combinations of IL-4 + IL-6 or IL-4 + IL-11, but not IL-4 alone, can substitute for PWM-SCM to reverse the inhibitory effect of IL-3 on B lymphoid potential. Neutralizing antibodies to IL-4 completely eliminated the activity in PWM-SCM, but antibodies to IL-6 only partially inhibited the activity. IL-11 was not detected in PWM-SCM, and the activity co-purified with IL-4, but not with IL-6. Thus, IL-4 plus IL-6, IL-11, or one or more unidentified growth factors in PWM-SCM can reverse the inhibitory effects of IL-3 on early B lymphocyte development in culture.

Animals↗

Dignity in dying: a preliminary study of patients in the last three days of life.

The final three days of life of 50 consecutive patients on a busy integrated palliative care service is described, with regard to final cause of death, symptom control, drug prescription, retention of personal function, and other measures possibly relevant to dignity in dying. Good symptom relief was maintained without rapid or high escalation of doses of morphine or sedatives. Personal function was maintained in at least a moderate degree in the majority of patients. This study also illustrates some of the difficulties in describing and evaluating the concept of "dying with dignity".

Activities of Daily Living↗

The human ovarian granulosa cell: a stereological approach.

The human ovarian granulosa cell is perhaps the most widely studied endocrine cell, but little quantitative structural information exists for this cell. In the present study new and traditional stereological probes have been employed to provide quantitative structural information on these functionally important cells. Granulosa cells were obtained from follicular aspirations from 10 women during in vitro fertilisation procedures. Initially 2 methods were used to estimate the mean nuclear volume of these cells: the mean number weighted nuclear volume was estimated by the Selector and the mean volume weighted nuclear volume by the point sampled intercept method. It was found that the difference between the 2 volume estimates was only 8.5%. The volume weighted mean nuclear volume was used as an estimate of nuclear volume. This was subsequently corrected (taking the percentage difference as the empirical bias) and combined with fractional cell volumes (Vv) to produce estimates of cell, mitochondrial, lipid and nucleolar volume. The proportion of the cell occupied by the nucleus had a remarkably low interindividual variation (CV = 7.6%). The proportion of the nucleus occupied by euchromatin also had a striking low variation (CV < 6%). All other cellular parameters had CVs of less than 35%. The lipid composition of these cells showed the greatest interindividual variability, with a CV of 42% for relative and 54% for absolute volume. The present study outlines a simple protocol for the quantitation of granulosa cell structure using new unbiased stereological probes and providing baseline structural information.

Cell Nucleus↗

Effects of early immune stress and changes in dietary metabolizable energy on the development of newly hatched turkeys. 1. Growth and nutrient utilization.

Two experiments were conducted to document the effects of an early immunologic stress and changes in dietary ME(n) on growth and nutrient utilization of newly hatched turkeys. Treatments in both experiments consisted of a complete factorial arrangement of two types of injection and four isonitrogenous diets. Turkeys were injected i.p. with saline (SAL) or a solution of lipopolysaccharide (LPS) (100 micrograms LPS/mL SAL) at 1, 3, and 5 d of age. In Experiment 1, two diets were formulated to contain 2,800 kcal ME(n)/kg. One was a corn-soybean meal-based diet (CSBM) and the other contained 8% Solkafloc (SKF). A third diet (3,100 kcal ME(n)/kg) was formulated by substituting 8% sucrose (SUC) for the 8% SKF. The fourth diet included in Experiment 1 was formulated to contain 3,700 kcal ME(n)/kg. The CSBM and SUC diets were also included in Experiment 2. Two additional diets tested in Experiment 2 were the CSBM diet containing 74.5 mg ibuprofen/kg (IBU) and a corn-soybean meal-based diet with a ME(n) value of 3,100 kcal/kg (CS31). Injection with LPS reduced (P < .05) BW of turkeys throughout Experiment 1 and until 9 d of age in Experiment 2, as compared with injection with SAL, irrespective of dietary treatment. The reduction in BW was mainly due to a decrease in feed intake (FI) (P < .05). Turkeys fed diets with 3,100 kcal ME(n)/kg were heavier (P < .05) than those fed diets with 2,800 kcal ME(n)/kg, irrespective of injection. Inclusion of ibuprofen to the CSBM diet from 1 to 14 d improved (P < .05) BW and feed efficiency (P < .01) of turkeys at 14 d of age, compared with turkeys fed the CSBM diet. Determined ME(n) was not affected by LPS injection. Adverse effects of LPS injection on growth of turkey poults were mainly the consequence of a reduced FI and not of altered nutrient utilization. These effects were not fully alleviated by feeding a diet with 3,100 kcal ME(n)/kg.

Animal Feed↗

Ciliary neurotropic factor, interleukin 11, leukemia inhibitory factor, and oncostatin M are growth factors for human myeloma cell lines using the interleukin 6 signal transducer gp130.

Interleukin 6 (IL-6) is a major growth factor for tumor plasma cells involved in human multiple myeloma (MM). In particular, human myeloma cell lines (HMCL), whose growth is completely dependent on addition of exogenous IL-6, can be obtained reproducibly from every patient with terminal disease. Four cytokines, ciliary neurotropic factor (CNTF), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OM), use the same transducer chain (signal transducer gp130) as IL-6 and share numerous biological activities with this IL. We found that these four cytokines stimulated proliferation and supported the long-term growth of two out of four IL-6-dependent HMCL obtained in our laboratory. Half-maximal proliferation was obtained with cytokine concentrations ranging from 0.4 to 1.2 ng/ml for IL-11, LIF, and OM. CNTF worked at high concentrations only (90 ng/ml), but addition of soluble CNTF receptor increased sensitivity to CNTF 30-fold. The growth-promoting effect of these four cytokines was abrogated by anti-gp130 antibodies, contrary to results for anti-IL-6 receptor or anti-IL-6 antibodies. No detectable changes in the morphology and phenotype were found when myeloma cells were cultured with one of these four cytokines instead of IL-6. Concordant with their IL-6-dependent growth, the four HMCL expressed membrane IL-6R and gp130 detected by FACS analysis. LIF-binding chain gene (LIFR) was expressed only in the two HMCL responsive to LIF and OM.

Antigens, CD↗

The Schizosaccharomyces pombe cdc5+ gene encodes an essential protein with homology to c-Myb.

The Schizosaccharomyces pombe cdc5+ gene was identified in the first screen for cell division cycle mutants in this yeast. The cdc5+ gene was reported to be required for nuclear division but because of its modest elongation and leaky nature at the non-permissive temperature, it was not investigated further. Here, we report the characterization of the single allele of this gene, cdc5-120, in more detail. The mutant arrests with a 2N DNA content and a single interphase nucleus. Further genetic analyses suggest that cdc5+ gene function is essential in the G2 phase of the cell cycle. We have cloned and sequenced the cdc5+ gene. The deduced protein sequence predicts that Cdc5 is an 87 kDa protein and contains a region sharing significant homology with the DNA binding domain of the Myb family of transcription factors. Deletion mapping of the cdc5+ gene has shown that the N-terminal 232 amino acids of the protein, which contain the Myb-related region, are sufficient to complement the cdc5ts strain. A cdc5 null mutant was generated by homologous recombination. Haploid cells lacking cdc5+ are inviable, indicating that cdc5+ is an essential gene. A fusion protein consisting of bacterial glutathione S-transferase joined in-frame to the N-terminal 127 amino acids of the Cdc5 protein is able to bind to DNA cellulose at low salt concentrations. This evidence suggests that cdc5+ might encode a transcription factor whose activity is required for cell cycle progression and growth during G2.

Amino Acid Sequence↗

Effect of culture in vitro and organ culture on the dry mass of preimplantation mouse embryos.

The dry mass of mouse embryos cultured in vitro in medium alone or in an organ culture system were measured by means of the Vickers M86 scanning microinterferometer. The data were compared with previous data on the dry mass of preimplantation embryos in vivo. The metabolism of embryos cultured in vitro differs from that of fresh embryos. In cultured embryos, dry mass decreases throughout the 2-cell stage whereas the dry mass is increasing at this stage in vivo. Embryos in an organ culture system regain a dry mass profile, similar to that observed in vivo at the late cleavage stage. These results support the view that conditions for embryo metabolism are suboptimal in vitro and that, although the oviduct may confer some advantage on developing embryos in vitro, it is unable fully to support the pattern of metabolism, as assessed by dry mass, observed in vivo.

Animals↗

Embryonic human chorionic gonadotropin secretion and hatching: poor correlation with cleavage rate and morphological assessment during preimplantation development in vitro.

Of 593 bipronucleate eggs allowed to develop in vitro, 275 (46%) achieved the blastocyst stage and beyond, 124 (21%) initiated hatching, but only 49 (8%) fully hatched. About half of the pre-embryos (48%) which developed to these more advanced stages were incapable of secreting significant amounts (> 200 microIU) of cumulative human chorionic gonadotropin (HCG) up to day 14. HCG production does not appear to begin until the expanded stage and is independent of hatching. Assessing cleavage rate through successive stages and morphological grades up to the 8-cell stage had little bearing on the ability of a pre-embryo to hatch or secrete HCG. Progression through the stages of preimplantation development in vitro does not always appear to be accompanied by the necessary biochemical stages. If only 46% of pre-embryos with two pronuclei are capable of achieving the blastocyst stage, and of these only 52% are capable of secreting HCG, then it follows that only 24% of the original bipronucleate pre-embryos in vitro can be considered anatomically and biochemically competent. However, this is only applicable for pre-embryos not transferred or frozen, and is thus subject to a selection bias. Inability to detect HCG in vitro is not conclusive proof that a pre-embryo is developmentally incompetent. Similarly failure to hatch in vitro may not be taken as definitive evidence that hatching would have failed had fertilization and development been completed in vivo. Nevertheless, if pre-embryonic development in vitro is similar to that in vivo, this may be a contributory factor in the low pregnancy rates following in-vitro fertilization treatment.

Blastocyst↗

Comparison of pyruvate uptake by embryos derived from conception and non-conception natural cycles.

The uptake of pyruvate by human embryos derived from natural cycles in the first 24 h following fertilization was examined. Since only one egg was obtained and therefore only one embryo transferred to the woman, it was possible to relate pyruvate consumption by a particular embryo to the outcome of that cycle (pregnancy or no pregnancy). The results showed that embryos have a wide range of pyruvate uptake values (2-53 pmol/embryo/h) but that this variation was reduced significantly to an intermediate range of values in those embryos that were able to implant (10-30 pmol/embryo/h). An association was found between embryo morphology and pyruvate consumption. Morphologically good embryos were more likely to implant if they demonstrated an intermediate pyruvate uptake. However, poor embryos did not implant even if they had a pyruvate uptake of 10-30 pmol/embryo/h. No relationship was found between the type of infertility and pyruvate consumption of individual embryos. It is suggested that the ability of an embryo to implant is multifactorial and that both morphology and pyruvate uptake may be factors.

Embryo, Mammalian↗

Synergistic effects of interleukin-11 with other growth factors on the expansion of murine hematopoietic progenitors and maintenance of stem cells in liquid culture.

The effect of interleukin-11 (IL-11), alone and in combination with other hematopoietic growth factors, was studied in liquid suspension cultures of murine bone marrow. Stem and progenitor cell contents of input bone marrow 2 days after 5-fluorouracil (5-FU) treatment (FU2dBM) and lineage-depleted, Sca-1-positive FU2dBM (Lin-Sca+Fu2dBM) were compared with output values obtained after 6 days in different growth factor combinations. Stem and progenitor cell recoveries were measured by long-term in vivo competitive repopulation, spleen colony-forming unit (CFU-S), and in vitro limiting dilution long-term bone marrow culture (cobblestone area-forming cell [CAFC]) assays. IL-11, IL-3, IL-6, and Steel factor (SF) were tested separately and in combinations of two, three, and four factors. IL-11 was incapable of maintaining the survival of stem or progenitor cells as a single agent but synergized with either IL-3 or SF to expand progenitor cell output in cultures of FU2dBM. IL-11 greatly enhanced progenitor cell expansion from FU2dBM when added to two- and three-factor combinations of SF, IL-3, and IL-6. The recovery of long-term repopulating ability was enhanced four-fold by incubation in SF plus IL-11 compared to SF alone. IL-11 in combination with SF, IL-3, and IL-6 stimulated a 24,000-fold expansion of progenitor cells from stem cell-enriched Lin-Sca+FU2dBM. Overall, the results indicate that IL-11 is a potent synergistic factor for stem cell proliferation and expansion of progenitors in liquid culture.

Animals↗

The biology of interleukin 11.

Interleukin 11 (IL-11) is a multifunctional cytokine which may play a role in regulating the growth and development of cells in both the hematopoietic and lymphoid systems. IL-11 activity was originally detected in the conditioned medium of a primate bone marrow stromal cell line, and the human cDNA was cloned from a human fetal lung fibroblast cell line. The purified protein shows multifunctional activity, influencing lymphohematopoietic stem cell proliferation and differentiation, megakaryocyte progenitor cell proliferation and differentiation, erythroid progenitor cell proliferation, B lymphocyte maturation, activation of hepatocyte acute phase protein synthesis, and adipogenesis. At the molecular level, IL-11 is unique, containing no asparagine-linked glycosylation sites and no cysteine residues. The IL-11 receptor belongs to a family of cytokine receptors which includes the receptors for IL-6, leukemia inhibitory factor (LIF), oncostatin M (OSM), and ciliary neurotrophic factor (CNTF), which are all capable of interacting with the signal transducing receptor gp130 after ligand binding. IL-11 has demonstrated activity in preclinical models for the treatment of thrombocytopenia and, in some cases, neutropenia; studies are underway to confirm its usefulness in the clinic for treatment of myelosuppression associated with cancer chemotherapy and bone marrow transplantation.

Animals↗

Smoke without fire: a reply to Hardy, Segatore and Edge.

Literacy is defined in the Oxford English Dictionary as the ability to read and write, and illiteracy as an inability to read. Hardy, Segatore and Edge (1993) suggest a serious problem of illiteracy among student nurses that endangers patient safety. Their evidence is entirely anecdotal, some of which is misclassified as literacy errors. They provide no substantive or statistical evidence to support their claims. Educators making serious and provocative charges on such flimsy grounds ought either to recant or obtain evidence that is more convincing.

Education, Nursing↗