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Biomedical subjects

D Ryan

Publications and source records attributed to D Ryan.

At least 19 recordsLinked to original sources
PubMed1997

Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila.

In both vertebrate and invertebrate development, cells are often programmed to adopt fates distinct from their neighbors. Genetic analyses in Drosophila melanogaster have highlighted the importance of cell surface and secreted proteins in these cell fate decisions. Homologues of these proteins have been identified and shown to play similar roles in vertebrate development. Fringe, a novel signalling protein, has been shown to induce wing margin formation in Drosophila. Fringe shares significant sequence homology and predicted secondary structure similarity with bacterial glycosyltransferases. Thus fringe may control wing development by altering glycosylation of cell surface and/or secreted molecules. Recently, two fringe genes were isolated from Xenopus laevis. We report here the cloning and characterization of three murine fringe genes (lunatic fringe, manic fringe and radical fringe). We find in several tissues that fringe expression boundaries coincide with Notch-dependent patterning centres and with Notch-ligand expression boundaries. Ectopic expression of murine manic fringe or radical fringe in Drosophila results in phenotypes that resemble those seen in Notch mutants.

Amino Acid Sequence↗
PubMed1995

Effect of aggressive daunomycin therapy on survival in acute promyelocytic leukemia.

The Southwest Oncology Group analyzed outcome with cytotoxic chemotherapy for previously untreated acute myeloblastic leukemia (AML) from 1982 through 1986. Results with acute promyelocytic leukemia (APL) prompted comparison with patients from 1986 through 1991 and analysis of factors contributing to APL results. Patient and disease characteristics and treatment outcome were compared for all evaluable patients, with more detailed analysis of factors affecting APL treatment outcome. From 1982 through 1986, median survival and disease-free survival in 45 APL patients were 106 months and greater than 105 months, respectively, versus 6 and 14 months for 417 other AML patients. Such differences were not seen from 1986 through 1991. In the 141 APL patients from 1982 through 1991, after adjusting for significant patient and disease characteristics, higher daunomycin (DNR) doses during induction were significantly associated with higher complete remission rates (P < .0001), longer survival (P < .0001), and longer DFS (P < .0001). Cytosine arabinoside (Ara-C) induction dose, the inclusion of other chemotherapy agents in induction, postremission therapy (consolidation, maintenance, or bone marrow transplantation) other than DNR, APL subtype, and patient age did not appear to significantly affect outcome of APL, except for a significant detrimental effect of high-dose Ara-C in consolidation (P = .0042). Morphologic AML subtypes other than APL did not affect outcome. We conclude that high-dose DNR selectively increases survival in APL. This good survival is important for evaluation of combined all-trans retinoic acid (ATRA)/chemotherapy protocols and for planning future combinations of chemotherapy and ATRA. These results illustrate the need to individualize chemotherapy for subtypes of AML. Therapeutic response of APL is independent of age. Except for APL, morphologic subclassification of AML contributed little prognostic information.

Adolescent↗
PubMed1995

Delayed omega-3 fatty acid supplements in renal transplantation. A double-blind, placebo-controlled study.

An earlier reported trial suggests that omega-3 fatty acids in fish oil supplements at 6 g/day with administration commencing at the time of engraftment may reduce acute CsA renal dysfunction. When started at the time of renal transplant, there are improvements in renal hemodynamics and blood pressure, and a decrease in rejection episodes. To examine the effect of later introduction of omega-3 fatty acids, 133 cadaver renal transplant recipients received CsA, prednisone, and AZA for 16 weeks (period 1). If patients were stable without rejection or infection activity, they were randomized to 9 g of eicosapentanoic acid (EPA), 18 g of EPA, 9 g of corn oil, or 18 g of corn oil in 1-g capsules as supplements. Glomerular filtration rate, renal blood flow, number of rejection episodes, blood pressure, and episodes of CsA nephrotoxicity were followed for 26 weeks in a double-blind manner (period 2). Ninety patients were evaluable and completed the protocol. There were 50 corn oil placebo patients, 22 low dose EPA patients, and 18 high dose EPA patients. In period 1, there were 27 rejection episodes in 21 patients without differences among subsequent treatment groups. In period 2, there were 13 rejection episodes in 4 patients. No patient with an EPA level in plasma statistically higher than placebo had a rejection episode. All allografts functioned for the entire 6 months with none lost to rejection. All 5 episodes of acute CsA nephrotoxicity occurred in placebo-treated patients without differences in whole blood CsA among toxic patients, other placebo patients, and EPA-treated recipients. At the end of the study, there were no differences in glomerular filtration rate, renal blood flow, or creatinine clearance among groups. Diastolic blood pressure fell by 9 mmHg during period 2 in high dose fish oil recipients and by 10 mmHg in low dose fish oil recipients (P < 0.05), while it rose by 2 mmHg in placebo patients. No serious adverse effects of EPA supplements were noted, although compliance based on plasma EPA was erratic. Based on our experience and that in the literature, administration of omega-3 fatty acids for purposes of kidney protection would seem to be most useful when started early after surgery. Late administration in our study was associated with minor clinical benefits.

Blood Pressure↗
PubMed1995

The cryopreservation of skin biopsies--a technique for reducing workload in a cell culture laboratory.

A method is described for the cryopreservation of skin biopsies at -70 degrees C for subsequent possible reculture. Biopsies stored up to 1 year could be successfully recultured without affecting the time to achieve confluence or the culture failure rate. This technique has been in operation in our department for over 3 years and has resulted in a demonstrable reduction in cell culture costs and a greater flexibility in the acceptance of skin biopsies for culture.

Biopsy↗
PubMed1995

Toxic metals in aquatic ecosystems: a microbiological perspective.

Microbe-metal interactions in aquatic environments and their exact role in transport and transformations of toxic metals are poorly understood. This paper will briefly review our understanding of these interactions. Ongoing research in Lake Chapala, Mexico, the major water source for the City of Guadalajara, provides an opportunity to study the microbiological aspects of metal-cycling in the water column. Constant resuspension of sediments provides a microbiologically rich aggregate-based system. Data indicate that toxic metals are concentrated on aggregate material and bioaccumulate in the food chain. A provisional model is presented for involvement of microbial aggregates in metal-cycling in Lake Chapala.

Animals↗
PubMed1994

Stem cell factor regulates human melanocyte-matrix interactions.

Stem cell factor (SCF) is hypothesized to play a critical role in the migration of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, c-kit, result in defects in coat pigmentation in mice and in skin pigmentation in humans. In this report we directly show that SCF alters the adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands and regulates integrin expression at the protein level. SCF decreased adhesion of neonatal and fetal cells to collagen IV, and increased attachment of fetal cells to laminin. Attachment of fetal cells to fibronectin was decreased, but was unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes showed that SCF down-regulated the expression of the alpha 2 receptor, and up-regulated the expression of the alpha 3, alpha 5 and beta 1 integrin receptors. SCF down-regulated expression of alpha 2, alpha 5 and beta 1 integrins by fetal melanocytes, and up-regulated expression of the alpha v and alpha 3 integrin receptors. Analysis of melanocyte migration using time-lapse videomicroscopy showed that SCF significantly increased migration of neonatal, but not fetal, melanocytes on fibronectin (FN). We conclude that SCF regulates integrin expression at the protein level and that SCF has pleiotropic effects on melanocyte attachment and migration on ECM ligands. We suggest that this may be one mechanism by which SCF regulates melanocyte migration during development of the skin.

Cell Adhesion↗
PubMed1994

Detection of Aeromonas salmonicida, causal agent of furunculosis in salmonid fish, from the tank effluent of hatchery-reared Atlantic salmon smolts.

The fish pathogen, Aeromonas salmonicida, could be detected only by bacteriological culture from the kidney of dead or moribund fish in one tank in a hatchery rearing Atlantic salmon (Salmo salar L.) smolts. However, by using a DNA probe specific for this species, allied to a PCR assay, the pathogen could be detected in water, feces and effluent samples taken from this fish tank. Also, the presence of the pathogen was found in effluent samples from two fish tanks containing apparently healthy fish. Subsequently, the presence of pathogen in these tanks was confirmed by an increase in the daily mortality rate and by a plate culture from moribund fish.

Aeromonas↗
PubMed1993

Autografting in chronic myelogenous leukemia followed by immunotherapy.

Patients with chronic myelogenous leukemia (CML) can be cured with allogeneic bone marrow transplantation. Over the past decade, it has become clear that immunological mechanisms, in the form of graft-versus-leukemia, constitute an integral part of this therapy. Because of limitations imposed by a lack of suitable donors, age, and toxicity, only a minority of patients can be offered allogeneic bone marrow transplantation (BMT). Recently, attempts have been made to employ autologous bone marrow transplantation (ABMT) for the therapy of CML using a variety of pre- and post-transplantation manipulations. This report describes the rationale for an ongoing clinical trial using the immunomodulator roquinimex (Linomide), following autologous bone marrow transplantation, in an attempt to stimulate the immunological responses thought to be critical for successful therapy in CML.

Adjuvants, Immunologic↗
PubMed1992

Fluorescent rhodol derivatives: versatile, photostable labels and tracers.

A series of chemically reactive, fluorescent rhodol derivatives was prepared and evaluated. Reactive functional groups included activated esters, amines, haloacetamides, fixable hydrazide derivatives, acrylamides, and photoaffinity reagents. Depending on the choice of substituents, absorption maxima of the dyes varied from 490 to 550 nm with extinction coefficients that were generally greater than 50,000 M-1 cm-1 in aqueous solution and emission maxima from 520 to 580 nm. Most of the compounds investigated exhibited fluorescence lifetimes between 3 and 4 ns. Individual derivatives were suitable for excitation with the 488 and 514-nm lines of the argon ion laser and the 546-nm line of the mercury arc lamp and were compatible for use with standard fluorescein and rhodamine filter sets. The rhodol dyes were more photostable and less sensitive to pH changes in the physiological range than fluorescein derivatives. Some examples show absorption maxima at or near 514 nm, an excitation wavelength that is useful for multicolor fluorescence microscopy, flow cytometry, and DNA sequencing. Derivatives were also prepared that exhibit absorption and emission maxima similar to those of tetramethylrhodamine (TMR) analogs but with higher quantum yields in aqueous solution. A number of the dyes had higher solubilities in aqueous systems and were less quenched on conjugation to proteins than TMR derivatives. Appropriate substitution results in a wider range of solubilities in hydrophilic or lipophilic solvents than is easily accomplished with fluorescein or TMR derivatives. Conjugates of a number of the rhodol fluorophores were generally more photostable and less pH sensitive than fluorescein conjugates and more fluorescent than TMR conjugates.

Affinity Labels↗
PubMed1992

High tech home care: a look at a success story.

The expansion of technology has allowed patients to receive intravenous therapy at home. This case study discusses the problems of a patient with diabetes mellitus and malignant otitis externa. This patient received intravenous therapy for the last 3 years of his life. In spite of several hospitalizations, he was able to return and remain home until his death. Management of the patient's discharge and home care seemed to be a major factor in his ability to remain in the community.

Adult↗
PubMed1991

Treatment of mild-to-moderate hypertension: comparison between a calcium-channel blocker and a potassium-sparing diuretic.

In a multicenter study, 61 patients, 18-70 years of age, with mild-to-moderate hypertension [diastolic blood pressure (DBP) 95/114] completed a 28-week treatment. After initial placebo washout, patients were randomly allocated either to diltiazem or hydrochlorothiazide/triamterene. At the end of 12 weeks, the patients continued on the same medication if their goal blood pressure achieved (DBP less than 90; or 10 mm Hg below baseline). If not, the alternate agent was added (either diltiazem + hydrochlorothiazide/triamterene or hydrochlorothiazide/triamterene + diltiazem). At the end of 28 weeks, the intent-to-treat analysis showed that 90% on diltiazem alone, 73.7% on hydrochlorothiazide/triamterene alone, 71.4% on (diltiazem + hydrochlorothiazide/triamterene), and 57.1% on (hydrochlorothiazide/triamterene + diltiazem) achieved goal BP. End point mean values of BP and heart rate after adjusting for sex, baseline values, age, and weight showed no significant difference between groups. Forty-six percent on hydrochlorothiazide/triamterene alone and 24% on diltiazem alone reported one or more adverse events, possibly related to study medication. Patients with diltiazem as the first choice had better BP control than those on hydrochlorothiazide/triamterene alone (81.5% vs. 69.7%). Furthermore, among non-goal achievers at week 12, there was a greater response in the group when hydrochlorothiazide/triamterene was added to diltiazem than when diltiazem was added to hydrochlorothiazide/triamterene. This study suggests that in mild-to-moderate hypertension, diltiazem is better than hydrochlorothiazide/triamterene as first line therapy.

Adolescent↗
PubMed1990

The clinical course of multiple sclerosis during pregnancy and the puerperium.

Eight women with multiple sclerosis were followed up through pregnancy. Clinical conditions, T-cell subsets, and levels of immunoactive pregnancy-associated proteins were measured twice during the pregnancy and twice during the first postpartum year. None of the women's conditions worsened during pregnancy, although one woman reported a slight increase of symptoms. Six of the eight women experienced relapses within the first 7 weeks after delivery. The number and percent of CD8 suppressor T cells were lower, and the CD4 helper-CD8 suppressor T-cell ratio was higher in the pregnant patients with multiple sclerosis compared with pregnant control women throughout pregnancy and the first 6 months post partum. There was no evident relationship between these parameters and clinical disease activity. Levels of alpha-fetoprotein, alpha 2-pregnancy-associated glycoprotein, and pregnancy-associated plasma protein A, all immunosuppressive proteins associated with pregnancy, were not significantly different in pregnant patients with multiple sclerosis and pregnant controls without multiple sclerosis. The study suggested that the risk of clinical relapse after delivery may be higher than has been reported previously. Furthermore, although there were differences in suppressor T cells, they were not predictably linked to changes in clinical disease activity.

Adult↗
PubMed1990

Arthrotomography and the surgical correction of temporomandibular joint disorders.

Over a 2-year-period, 321 new patients were seen at one clinic with temporomandibular joint dysfunction and pain. Sixty-seven (21%) of these who did not respond to 12 weeks medical therapy, had arthrotomography performed and 24 patients (7.5%) underwent surgery to the joint. Eighteen (75%) of these patients were free of pain 1 year later, although this success was not always sustained without medical therapy. Meniscus adhesions were under-estimated on arthrotomography compared to surgical findings and meniscus perforations were over diagnosed. However, increased accuracy in preoperative diagnosis was seen with experience. There was only one false positive result which lead to unnecessary surgery.

Adult↗
PubMed1990

Molecular dosimetry of DNA adducts in Chinese hamster ovary cells and C3H10T1/2 mouse embryo fibroblast cells treated with benzo[a]pyrene.

Chromatographic profiles of DNA adducts formed following treatment of Chinese hamster ovary (CHO) cells or C3H10T1/2 mouse embryo fibroblast cells with benzo[a]pyrene (BP), in the presence or absence of rat liver S9 fraction, have been obtained by both direct labelling ([3H]BP) and 32P-post-labelling methods. The principal adduct formed in both cell lines was (+)-N2-(7R,8S,9R-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene- 10S-yl) 2'-deoxyguanosine (detected as its 3',5'-bisphosphate by 32P-post-labelling). In both cell lines significantly higher levels of adducts were observed in the presence of S9 fraction. The results of these studies provide useful reference data on the genotoxic metabolism of BP in these widely used cell culture systems and allow comparisons with data obtained in other experimental mammalian systems. Valid comparisons of metabolism in experimental systems used as extrapolative models for man are particularly important where multiple bioactivation pathways are possible, such as in the case of polycyclic aromatic hydrocarbons.

Animals↗
PubMed1990

Obstetrics without an on site paediatrician.

A ten year review (1980-89) of Wexford perinatal statistics is presented. Particular emphasis was placed on neonatal deaths and transfer rates of normally formed infants. Increased visits by paediatricians in the last two years have been associated with an increased neonatal transfer rate to a regional unit 40 miles away. Neonatal mortality rates have not improved, though any beneficial effects on infant morbidity was not assessed. The case for on site paediatric expertise with at least two consultants to provide a continuous service is argued.

Birth Weight↗