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W Davis

Publications and source records attributed to W Davis.

At least 37 records · Page 2Linked to original sources
PubMed1999

Chronic pneumonia caused by Mycobacterium thermoresistibile in a cat.

Mycobacterium thermoresistibile was isolated in pure culture from ultrasound-guided pulmonary aspirates taken from a young cat with severe, chronic, pyogranulomatous pneumonia. Thoracic radiography and ultrasonography before therapy demonstrated severe diffuse alveolar disease. Twelve months combination therapy with doxycycline, rifampicin and clarithromycin resolved the infection. Thoracic radiographs taken at the completion of therapy showed multifocal pulmonary mineralisation. M thermoresistibile has been infrequently reported as a human or animal pathogen. This is the first reported pulmonary infection by M thermoresistibile in a cat and documents the successful treatment of the organism in a feline patient.

Animals↗
PubMed1999

Comparison of custom and prefabricated orthoses in the initial treatment of proximal plantar fasciitis.

Fifteen centers for orthopaedic treatment of the foot and ankle participated in a prospective randomized trial to compare several nonoperative treatments for proximal plantar fasciitis (heel pain syndrome). Included were 236 patients (160 women and 76 men) who were 16 years of age or older. Most reported duration of symptoms of 6 months or less. Patients with systemic disease, significant musculoskeletal complaints, sciatica, or local nerve entrapment were excluded. We randomized patients prospectively into five different treatment groups. All groups performed Achilles tendon- and plantar fascia-stretching in a similar manner. One group was treated with stretching only. The other four groups stretched and used one of four different shoe inserts, including a silicone heel pad, a felt pad, a rubber heel cup, or a custom-made polypropylene orthotic device. Patients were reevaluated after 8 weeks of treatment. The percentages improved in each group were: (1) silicone insert, 95%; (2) rubber insert, 88%; (3) felt insert, 81%; (4)stretching only, 72%; and (5) custom orthosis, 68%. Combining all the patients who used a prefabricated insert, we found that their improvement rates were higher than those assigned to stretching only (P = 0.022) and those who stretched and used a custom orthosis (P = 0.0074). We conclude that, when used in conjunction with a stretching program, a prefabricated shoe insert is more likely to produce improvement in symptoms as part of the initial treatment of proximal plantar fasciitis than a custom polypropylene orthotic device.

Adult↗
PubMed1999

Aortic root geometry: pattern of differences between leaflets and sinuses of Valsalva.

BACKGROUND AND AIMS OF THE STUDY: Growing interest in aortic root replacement with the use of stentless auto-, homo- and xenografts, and new developments in aortic valve conservation demand a deeper understanding of the normal aortic root anatomy. METHODS: Ten cryopreserved human aortic roots were pressurized, fixed and measured directly (leaflet free edge and attachment) and using three-dimensional computed tomography imaging software (sinus of Valsalva height and volume). RESULTS: The mean of the measurements of all four parameters yielded a pattern in which the non-coronary sinus (N) structures had the greatest dimensions followed by the right (R) and then the left (L). Non-parametric ANOVA on each of these parameters also showed significant differences among the sinuses yielding a pattern of N > R > L. This pattern determined an angle of tilt between the plane at the base (annulus) and the plane intersecting the sinotubular junction with a mean value of 11 degrees. Linear regression indicated that this angle did not depend on the size of the base (annulus). CONCLUSIONS: The data showed a geometric pattern of the aortic root, with the structures of the non-coronary sinus being the largest followed by the right and then the left. The possible hemodynamic relevance and surgical implications of these findings need to be explored.

Aortic Valve↗
PubMed1998

Molecular cloning and expression of the mouse translation initiation factor eIF-1A.

Prior to determining the molecular basis for the transient increase in expression of eIF-1A during the 2-cell stage of the pre-implantation mouse embryo, we determined the sequence of full-length cDNA and defined properties of the genomic organization of the mouse eIF-1A gene. Northern blot analysis distinguishes three transcripts in mouse liver of 2.8, 2.2 and 1.9 kb in size. The three transcripts arise from initiation at two putative promoters separated by 627 bp. Initiation from the putative distal promoter yields both the 2.8 and 1.9 kb transcripts, in which the 1.9 kb transcript is generated by alternative splicing of 840 bp of intervening RNA. The putative distal promoter, which lacks both a TATA box and CCAAT box control elements but contains several GC-rich clusters, initiates transcription at two start sites that are separated by 30 bp. Thus, four transcripts are generated from the distal promoter. The putative proximal promoter that directs transcription of a single 2.2 kb mRNA is preceded by a TATA box element that binds TBP. Each of the promoters is used by the pre-implantation mouse embryo, since we have been able to amplify selectively each of the five individual eIF-1A transcripts initiated from each promoter and start site in the 2-cell mouse embryo.

5' Untranslated Regions↗
PubMed1998

Inhibition by an extract of Ocimum sanctum of DNA-binding activity of 7,12-dimethylbenz[a]anthracene in rat hepatocytes in vitro.

Ocimum sanctum is a traditional medicinal plant. Previous studies have shown that extracts of O. sanctum inhibit the induction of skin papillomas in mice by 7,12-dimethylbenz[a]anthracene (DMBA). In the present study, primary cultures of rat hepatocytes were treated with 0-500 microg of O. sanctum extract for 24 h and then with DMBA (10 or 50 microg) for 18 h. Cells were then harvested and their DNA was isolated and analyzed by 32P-postlabelling. A significant reduction in the levels of DMBA-DNA adducts was observed in all cultures pretreated with O. sanctum extract. This effect was more pronounced at the lower dose of DMBA (10 microg). Hepatocytes which were treated with the highest dose of extract (500 microg) showed a maximum reduction of 93% in the mean values of DMBA-DNA adducts. The viability of the cells was not adversely affected by pretreatment with extract. Our findings suggest that O. sanctum leaf extract blocks or suppresses the events associated with chemical carcinogenesis by inhibiting metabolic activation of the carcinogen.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1998

Report of the Second Equine Leucocyte Antigen Workshop, Squaw valley, California, July 1995.

The final assignment of antibody clusters for leucocyte antigens and immunoglobulins, as described in detail in Sections 3 and 4, is summarized in Table 4. Together with other mAbs developed outside of ELAW II (Table 9) this pool of reagents represent a powerful array of tools for the study of equine immunity. The Second Equine Leucocyte Antigen Workshop made considerable advances in pursuing the objectives of establishing the specificities of mAbs and achieving consensus on the nomenclature for equine leucocyte and immunoglobulin molecules. Of equal importance, several productive collaborations were fostered among the participating laboratories and observers. Overall, enormous advances have been made in the past decade since mAbs specific for equine leucocyte antigens and immunoglobulins were first reported. There remains enormous scope and need for further studies of equine leucocyte antigens and immunoglobulins, both for the purposes of comparative immunology and for the good of the horse. In the future novel techniques will be required to develop reagents for specific target antigens such as the orthologues of the CD25 or CD45 isoforms. In studies of equine immunoglobulins the functional role of the IgG isotypes must be better established, reagents for IgE must be developed, and cloning of the immunoglobulin heavy chain genes will be essential if the complexities of the IgG sub-isotypes are to be elucidated. The tasks still facing the currently small group of equine immunologists throughout the world remain formidable, and will only be tackled successfully in a spirit of collaboration.

Animals↗
PubMed1998

Summary of workshop findings for antibodies reacting with porcine T-cells and activation antigens: results from the Second International Swine CD Workshop.

After initial evaluation of the 176 new and 19 control monoclonal antibodies (mAb) submitted to the Second International Swine CD Workshop, 57 were assigned to the T-cell/activation marker subgroup. These 57 mAb were further analyzed using flow cytometry on whole blood lymphocytes, splenocytes, Peyer's patch lymphocytes, in vitro cell lines, broncho-alveolar lavage cells, Con A and PHA blasts, fetal cell populations, and by 2-color flow cytometry against mAb to porcine CD2, CD4, and CD8. Finally, the molecular weights of the target antigens were characterized when possible. As a result of these analyses, 23 mAb were distributed into 7 CD clusters. Newly confirmed mAb assignments included: two CD2; one CD4; two CD5; one wCD6; and one wCD25. Three new mAb were found that reacted with wCD8, one of which defined a new epitope, wCD8c. For the first time, mAb against porcine CD3 were identified, including 6 mAb that reacted with three different epitopes. Several new mAb reacted with antigens whose expression varied depending on the activation state of the test cell. These will require further characterization in order to assign a CD number.

Animals↗
PubMed1998

Tacrolimus: a new agent for the prevention of graft-versus-host disease in hematopoietic stem cell transplantation.

Tacrolimus (FK506) is a macrolide lactone with potent immunosuppressive activity 100 times that of cyclosporine by weight. The molecular mechanism of action is mediated via an inhibition of the phosphorylase activity of calcineurin by drug-immunophilin complex, resulting in the inhibition of IL-2 gene expression. There are emerging studies now showing significant efficacy of tacrolimus in GVHD prevention in both related and unrelated donor transplantation. Three multicenter randomized studies comparing tacrolimus to cyclosporine have been completed, one each in related and unrelated donor transplantation; the remaining study involved both related and unrelated donor transplantation. All three studies showed a significantly lower incidence of grade II-IV acute GVHD in patients who received tacrolimus. One study in sibling donor transplantation showed that patients with advanced disease who received tacrolimus had a poorer survival than patients who received cyclosporine, but the survival was similar in patients with non-advanced disease. The remaining two studies, one in unrelated donors and the other combining both related and unrelated donors did not show any survival difference between the tacrolimus and cyclosporine groups. In addition, this review also highlights some of the critical questions regarding the role of this agent in allogeneic stem cell transplantation: (1) the contribution of methotrexate in combination with tacrolimus; (2) the starting i.v. dose of tacrolimus; (3) the suggested whole blood level of tacrolimus and its effect on nephrotoxicity; and (4) whether tacrolimus should be used in patients with advanced malignancy. Future studies using tacrolimus in combination with other immunosuppressants, and its use in patients with advanced malignancy will be warranted.

Acute Disease↗
PubMed1998

Symptom control in patients with hay fever in UK general practice: how well are we doing and is there a need for allergen immunotherapy?

BACKGROUND: Seasonal allergic rhinitis is often regarded as a trivial condition which patients should treat themselves. However, a significant proportion of sufferers are not fully controlled on standard hay fever medication, either because they do not use it properly or because their symptoms are resistant to standard therapy. The latter group may be suitable for allergen immunotherapy, which was once widely available in UK general practice but is now only available through specialist centres. AIMS: To describe the symptom control of patients with hay fever, to assess concordance with prescribed medication, and to estimate the number of patients who may benefit from referral for allergen immunotherapy. SETTING: General practices in Hampshire and Dorset, UK. METHOD: Survey of adult hay fever sufferers prescribed a non-sedating antihistamine and nasal steroid spray by their general practitioner. A postal questionnaire was sent to all eligible patients aged 16-64 registered with 16 general practices. Self-assessment of symptom control and reported compliance with medication were used to identify those patients who were suboptimally controlled and might therefore benefit from immunotherapy. RESULTS: Eight hundred and forty-six out of 62500 registered patients aged 16-64 (1.4%) were receiving both drugs, and responses were received from 627 (74.1%); 526 of these met the full entry criteria. One hundred and forty-two patients (27.0%) were using both types of drug regularly. Of the 142 patients using optimum pharmacotherapy, 54 (38.0%) reported good control of their hay fever symptoms. The remaining 62.0% experienced troublesome residual symptoms and described symptom control as partial or poor. Among those using suboptimal pharmacotherapy, 181/376 (48.1%) reported good control. CONCLUSION: Many patients are using treatment inappropriately. Current guidelines need to be applied better but there is also a significant burden of residual symptoms, even among those receiving current optimal therapy. This indicates a need for patients with severe summer hay fever to receive specialist assessment.

Adolescent↗
PubMed1998

Lysosomal routing of Fc gamma RI from early endosomes requires recruitment of tyrosine kinases.

The high-affinity receptor for immunoglobulin G (Fc gamma RI) plays a central role in the clearance of immune complexes by mediating their internalization and delivery to lysosomes. In monocytic U937 cells, receptor internalization is independent of tyrosine kinase activity. However, the tyrosine kinase inhibitor, genistein, prevents further progress of the receptor to lysosomes and traps it in a sub-plasma membrane early endosome. Similarly, Fc gamma RI expressed in COS cells is able to internalize immune complexes but is unable to translocate to lysosomes. This suggests that Fc gamma RI, whose cytoplasmic tail is devoid of known signalling motifs, must recruit tyrosine kinases via its gamma-chain to achieve lysosomal delivery. We show that a chimera of the extracellular domain of Fc gamma RI and the cytoplasmic tail of the gamma-chain is both internalized and efficiently trafficked to lysosomes. Our study suggests that a key function of the gamma-chain is recruitment of tyrosine kinases to initiate the intracellular signalling pathways required to target Fc gamma RI following immune complex aggregation to lysosomes and not to initiate endocytosis per se.

Antigen-Antibody Complex↗
PubMed1998

Rat, but not human, sulfotransferase activates a tamoxifen metabolite to produce DNA adducts and gene mutations in bacteria and mammalian cells in culture.

Tamoxifen increases the risk of human endometrial cancer and is a potent carcinogen in rat liver, in which it produces DNA adducts and cytogenetic damage. Nevertheless its prophylactic use against breast cancer in healthy women is under investigation in several large trials. To investigate whether rat hepatocarcinogenicity predicts human hepatocarcinogenicity we used genetically engineered bacterial and mammalian target cells to investigate how alpha-hydroxy-tamoxifen, a major phase I metabolite of tamoxifen, is further metabolised by rat and human phase II enzymes, sulfotransferases, to mutagenic and DNA-adduct-forming species. We expressed rat hydroxysteroid sulfotransferase a, a liver-specific enzyme, and corresponding human sulfotransferase in bacteria (Salmonella typhimurium) and in a mammalian cell line (Chinese hamster V79 cells) and tested alpha-hydroxytamoxifen for DNA adduct formation and mutagenicity in these systems, using unmodified cells as controls. In cells that expressed rat hydroxysteroid sulfotransferase, alpha-hydroxytamoxifen was mutagenic and formed the same pattern of DNA adducts as that found in the liver of tamoxifen-treated rats. Alpha-hydroxytamoxifen was not activated, or was at least 20 times less active in cells expressing human hydroxysteroid sulfotransferase. All the other six known human xenobiotic-metabolising sulfotransferases were also expressed in S. typhimurium. None activated alpha-hydroxytamoxifen to a mutagen. These results suggest that the risk of DNA adduct formation, and cancer, in the human liver is low and explain why tamoxifen is a powerful carcinogen to the rat liver, and why standard short-term tests fail to detect its mutagenicity.

Animals↗
PubMed1998

The metabolic activation of tamoxifen and alpha-hydroxytamoxifen to DNA-binding species in rat hepatocytes proceeds via sulphation.

The biotransformation pathway of tamoxifen and alpha-hydroxytamoxifen to DNA-binding species was investigated in rat hepatocytes in vitro. Rat hepatocytes were isolated by in situ collagenase perfusion and then maintained in sulphate-free Dulbecco's modified Eagle's medium. Magnesium sulphate was added to the medium to give concentrations of 0-10 microM, prior to treatment for 18 h with solvent vehicle (DMSO), tamoxifen (10 microM), alpha-hydroxytamoxifen (1 microM) or benzo[a]pyrene (BaP) (10 and 50 microM). DNA was isolated and analysed by 32P-post-labelling. For tamoxifen and alpha-hydroxytamoxifen, the level of DNA adduct formation was directly proportional to the concentration of sulphate in the medium. Between 0 and 10 microM MgSO4, the DNA adduct level increased 10-fold with both compounds. Rat hepatocytes were also maintained in normal Dulbecco's modified Eagle's medium and pretreated with dehydroisoandrosterone-3-sulphate (DHEAS, a sulphotransferase inhibitor) at concentrations ranging from 0-1 mM, prior to treatment with solvent vehicle (DMSO), tamoxifen (10 microM), alpha-hydroxytamoxifen (1 microM) or BaP (50 microM). For tamoxifen and alpha-hydroxytamoxifen the level of DNA adducts was reduced to approximately one-fifth by the addition of DHEAS (0.1 mM). BaP-DNA adduct formation, which proceeds by a pathway that does not require sulphation, was not significantly affected by sulphate concentration or by addition of DHEAS, which demonstrates that the general metabolic capacity and viability of the hepatocytes were not compromised. It is concluded that the activation of tamoxifen in rat liver cells to DNA binding products proceeds predominantly through hydroxylation followed by sulphate ester formation at the alpha-position of the ethyl side chain.

Animals↗
PubMed1997

Jun NH2-terminal kinase is constitutively activated in T cells transformed by the intracellular parasite Theileria parva.

When T cells become infected by the parasite Theileria parva, they acquire a transformed phenotype and no longer require antigen-specific stimulation or exogenous growth factors. This is accompanied by constitutive interleukin 2 (IL-2) and IL-2 receptor expression. Transformation can be reversed entirely by elimination of the parasites using the specific drug BW720c. Extracellular signal-regulated kinase and jun NH2-terminal kinase (JNK) are members of the mitogen-activated protein kinase family, which play a central role in the regulation of cellular differentiation and proliferation and also participate in the regulation of IL-2 and IL-2 receptor gene expression. T. parva was found to induce an unorthodox pattern of mitogen-activated protein kinase expression in infected T cells. JNK-1 and JNK-2 are constitutively active in a parasite-dependent manner, but have altered properties. In contrast, extracellular signal-regulated kinase-2 is not activated even though its activation pathway is functionally intact. Different components of the T cell receptor (TCR)-dependent signal transduction pathways also were examined. The TCRzeta or CD3epsilon chains were found not to be phosphorylated and T. parva-transformed T cells were resistant to inhibitors that block the early steps of T cell activation. Compounds that inhibit the progression of T cells to proliferation, however, were inhibitory. Our data provide the first example, to our knowledge, for parasite-mediated JNK activation, and our findings strongly suggest that T. parva not only lifts the requirement for antigenic stimulation but also entirely bypasses early TCR-dependent signal transduction pathways to induce continuous proliferation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1997

Role of the first round of DNA replication in reprogramming gene expression in the preimplantation mouse embryo.

The first round of DNA replication has been proposed to provide a window of opportunity for maternally-derived transcription factors to gain access to their cognate cis-binding DNA sequences and thereby reprogram the pattern of gene expression that occurs during the 2-cell stage. Using high-resolution, two-dimensional electrophoresis of metabolically radio-labeled polypeptides, we report the expression of a group of several polypeptides whose synthesis in the 2-cell embryo is due to transcription (i.e., alpha-amanitin-sensitive) and depends on the first round of DNA replication (i.e., aphidicolin-sensitive). We also describe the synthesis of another subset of alpha-amanitin-sensitive polypeptides whose expression does not require the first round of DNA replication (i.e., aphidicolin-insensitive). These results are consistent with the proposed role of the first round of DNA replication in reprogramming the pattern of gene expression.

Amanitins↗
PubMed1997

The metabolic profile of glucose tolerant women who have had large for gestational age babies.

The possibility has been raised that women who have had large for gestational age infants, while glucose tolerant during pregnancy by conventional testing, may still have a subtle abnormality of carbohydrate metabolism. We have examined, some time after the completion of a pregnancy, the fasting levels of glucose, insulin and lipids in a group of women, glucose tolerant during pregnancy, who had a large for gestational age infant compared to a very carefully matched control group of women who had an appropriate for gestational age infant. No significant differences were found. These findings suggest that women who have a large for gestational age infant do so for a variety of reasons not related to maternal carbohydrate metabolism.

Blood Glucose↗
PubMed1997

The accuracy of home glucose meters for the glucose range anticipated in pregnancy.

Home glucose meters are used almost universally for the management of pregnant women with diabetes. However, the degree of accuracy of meters in general and particularly for the lower glucose range, is questionable. Six of the most commonly used meters in Australia were evaluated for analytical accuracy for glucose levels < 8.0 mmol/L--a level below which many important clinical management decisions are made. Two meters, Elite and Precision QID, cannot be recommended. The other 4 meters, Glucometer 3, Reflolux S, Alpha and Advantage produced results with a higher degree of analytical accuracy. Of the meters tested, the Accutrend Alpha had the highest proportion of results within 5% and 10% of a laboratory reference method, the lowest bias with the Altman Bland method of comparison, and is recommended for use in pregnancy. No meter approached the analytical accuracy goal recommended by the American Diabetes Association. Manufacturers should be encouraged to develop or adapt systems for use in pregnancy.

Adult↗
PubMed1996

Transient expression of translation initiation factor eIF-4C during the 2-cell stage of the preimplantation mouse embryo: identification by mRNA differential display and the role of DNA replication in zygotic gene activation.

Zygotic gene activation (ZGA) definitely occurs by the 2-cell stage in the mouse embryo. Analysis of protein synthesis by two-dimensional gel electrophoresis reveals a class of genes whose expression transiently increases in the 2-cell embryo. Although the paucity of biological material has prevented a systematic identification of these genes, the mRNA differential display method circumvents this problem. Using this approach we find a transient increase in the mRNA abundance of the translation initiation factor eIF-4C that is inhibited by alpha-amanitin and correlated with a transient increase in the relative rate of protein synthesis for eIF-4C. We confirm the transient increase in eIF-4C mRNA abundance by a reverse transcription-PCR-based assay using eIF-4C-specific primers. The first round of DNA replication seems critical for eIF-4C expression, since addition of aphidicolin prior to S phase in the 1-cell embryo inhibits the magnitude of the increase in eIF-4C expression. Aphidicolin treatment also inhibits the synthesis of an accepted marker for ZGA, the transcription requiring complex (TRC), which is also transiently expressed during the 2-cell stage. Incubating late 1-cell/early 2-cell embryos in medium containing aphidicolin reveals that the second round of DNA replication is not required for the increase in eIF-4C expression but DNA replication is required for the decrease in both eIF-4C expression and TRC synthesis. The decrease in eIF-4C expression, however, does not require cytokinesis or mitosis, since it occurs when 2-cell embryos are cultured in the presence of cytochalasin D or nocodazole, respectively. Changes in chromatin structure may be involved in the decrease in both eIF-4C and TRC expression, since neither decrease occurs when 2-cell embryos are cultured in trapoxin, which is a specific and irreversible inhibitor of histone deacetylase. Results of these experiments suggest that the first round of DNA replication is permissive with respect to ZGA and that the second round is repressive.

Acetylation↗