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Biomedical subjects

C E Rogers

Publications and source records attributed to C E Rogers.

At least 19 recordsLinked to original sources
PubMed2001

Fuc-TVII is required for T helper 1 and T cytotoxic 1 lymphocyte selectin ligand expression and recruitment in inflammation, and together with Fuc-TIV regulates naive T cell trafficking to lymph nodes.

To determine how the alpha(1,3)fucosyltransferases Fuc-TIV and Fuc-TVII, and the selectin ligands they control may contribute to the adaptive immune response, contact hypersensitivity (CHS) was characterized in mice deficient in either or both enzymes. We find a substantial CHS deficiency in Fuc-TVII(-/-) mice, and a complete deficiency in Fuc-TIV(-/-)/Fuc-TVII(-/-) mice. These defects are not accounted for by alterations in the number or function of epidermal Langerhans cells required for cutaneous antigen processing and presentation. By contrast, defective CHS in Fuc-TVII(-/-) mice or Fuc-TIV(-/-)/Fuc-TVII(-/-) mice is attributed in part to prominent, or nearly complete deficiencies, respectively, in the complement of naive T lymphocytes available in lymph nodes for antigen-dependent activation, expansion, differentiation, and dissemination. Fuc-TVII deficiency also deletes expression of E- and P-selectin ligands by Th1 and T cytotoxic 1 (Tc1) lymphocytes, annuls T cell trafficking to inflamed cutaneous sites in vivo, and thereby controls an essential component of the efferent phase of the cutaneous immune response. These observations indicate that collaborative contributions of Fuc-TIV and Fuc-TVII to L-selectin ligand synthesis, and to lymphocyte recruitment, are requisite components of the primary cellular immune response, and assign an essential role to Fuc-TVII in control of E- and P-selectin ligand expression by Th1 and Tc1 lymphocytes.

Animals↗
PubMed2001

The alpha(1,3)fucosyltransferases FucT-IV and FucT-VII exert collaborative control over selectin-dependent leukocyte recruitment and lymphocyte homing.

E-, P-, and L-selectin counterreceptor activities, leukocyte trafficking, and lymphocyte homing are controlled prominently but incompletely by alpha(1,3)fucosyltransferase FucT-VII-dependent fucosylation. Molecular determinants for FucT-VII-independent leukocyte trafficking are not defined, and evidence for contributions by or requirements for other FucTs in leukocyte recruitment is contradictory and incomplete. We show here that inflammation-dependent leukocyte recruitment retained in FucT-VII deficiency is extinguished in FucT-IV(-/-)/FucT-VII(-/-) mice. Double deficiency yields an extreme leukocytosis characterized by decreased neutrophil turnover and increased neutrophil production. FucT-IV also contributes to HEV-born L-selectin ligands, since lymphocyte homing retained in FucT-VII(-/-) mice is revoked in FucT-IV(-/-)/FucT-VII(-/-) mice. These observations reveal essential FucT-IV-dependent contributions to E-, P-, and L-selectin ligand synthesis and to the control of leukocyte recruitment and lymphocyte homing.

Animals↗
PubMed1997

The establishment of current opinion within consultants in paediatric dentistry in the UK for the taking of dental radiographs of children.

There is an increasing realization that every effort should be made to minimize the exposure to ionizing radiation of patients and members of the dental team. There are, however, few published guidelines to assist the general practitioner in deciding whether or not radiographs are needed. There is even less information concerning the taking of dental radiographs of children. Using the Delphi Technique this study set out to seek a consensus amongst Consultant Paediatric Dentists (n = 36) working in the UK as to when dental radiographs should and should not be taken of children cared for within general dental services. A two-stage questionnaire was used and a response of 94% and 76% was obtained in the first and second questionnaire respectively. A consensus view was reached regarding whether or not radiographs should be taken in a series of 17 specific clinical situations.

Child↗
PubMed1997

Hair analysis does not support hypothesized arsenic and chromium exposure from drinking water in Woburn, Massachusetts.

We hypothesized that residents of Woburn, Massachusetts, had been exposed to as much as 70 microg/l of arsenic (As) and 240 microg/l of chromium (Cr) in drinking water from municipal supply wells G and H. To test this hypothesis, we measured the concentrations of As and Cr in 82 hair samples donated by 56 Woburn residents. Thirty-six samples were cut between 1964 and 1979, the period during which wells G and H were in operation. The remainder were cut either before 1964 (1938-1963; n = 26) or after 1979 (1982-1994; n = 20). Washed hair samples were analyzed by instrumental neutron activation. Exposure to the well water--measured as access--was estimated using well pumping records and a model of the Woburn water distribution system. Our results show that access to wells G and H water was not significantly correlated (95% confidence interval) with As and Cr concentrations measured in the hair of Woburn residents, but As concentrations have declined significantly over the last half century. Linear regression of As concentrations (micrograms per gram) upon year of hair cut and access to wells G and H water yielded a standard coefficient for year of -0. 0074 +/- 0.0017 (standard error; p = 2.5 -multiple- 10(-5)) and -0.12 +/- 0.10 (p = 0.22) for access. The r2 value for the model was 0.19. The geometric mean concentrations (geometric standard deviation) of As and Cr in the hair of residents who had access (i.e., relative access estimate >0) to wells G and H water (n = 27) were 0.14 (2.6) and 2.29 (1.8) microg/g, respectively; the geometric mean concentrations of As and Cr in all of the hair samples from residents who did not have access (1938-1994; n = 55) were 0.13 (3.0) and 2.19 (2.0) microg/g, respectively.

Adult↗
PubMed1996

The alpha(1,3)fucosyltransferase Fuc-TVII controls leukocyte trafficking through an essential role in L-, E-, and P-selectin ligand biosynthesis.

alpha(1,3)Fucosylated oligosaccharides represent components of leukocyte counterreceptors for E- and P-selectins and of L-selectin ligands expressed by lymph node high endothelial venules (HEV). The identity of the alpha(1,3)fucosyltransferase(s) required for their expression has been uncertain, as has a requirement for alpha(1,3)fucosylation in HEV L-selectin ligand activity. We demonstrate here that mice deficient in alpha(1,3) fucosyltransferase Fuc-TVII exhibit a leukocyte adhesion deficiency characterized by absent leukocyte E- and P-selectin ligand activity and deficient HEV L-selectin ligand activity. Selectin ligand deficiency is distinguished by blood leukocytosis, impaired leukocyte extravasation in inflammation, and faulty lymphocyte homing. These observations demonstrate an essential role for Fuc-TVII in E-, P-, and L-selectin ligand biosynthesis and imply that this locus can control leukocyte trafficking in health and disease.

Animals↗
PubMed1996

Flow cytometric analysis of human bone marrow perfusion cultures: erythroid development and relationship with burst-forming units-erythroid.

Flow cytometry has been used in recent years to study antigenic and physical changes accompanying hematopoietic cell differentiation. Such studies have provided the basis for rapid and objective assays that are potential alternatives to the colony assays currently in widespread use. In this report, erythropoiesis was examined in growth factor-supplemented perfused cultures of bone marrow mononuclear cells (BMMNC) using flow cytometric analysis of the transferrin receptor (CD71), glycophorin antigen expression occurred with time, Initially, fewer than 10% of the cells were (CD71++, but by day 8, 19-34% of the cells were CD71++gly A-. This was followed by the appearance of gly A on 10-60% of the CD71++ cells. After day 10, CD71 expression on many gly A+ cells decreased so that a population of CD71-gly A+ cells (11-54 accumulated by day 14. Each phenotype was sorted for morphologic identification and colony assay analysis. CD71++gly A- cells were 85% blasts, one-half of which were erythroblasts, and were significantly enriched for burst-forming units-erythroid (BFU-E). The time-varying number of CD71++gly A- cells in these cultures was found to correlate with the number of BF.78-0.97). Three-color analysis was next used to examine CD33 expression on BFU-E, and in fresh BM, most were found to be CD33-. During culture, however, the number of BFU-E recovered from CD33+ populations first increased and then decreased. Therefore, CD33 was not particularly useful for identifying BFU-E. In contrast, CFU-GM were mostly found to be in the CD71+CD33+ population throughout the culture period. When erythropoietin (Epo) was not added to these cultures, the percentage of gly A+ cells was reduced from 33 to 3.3%. Further, the omission of Epo caused an 80% decrease in the number of BFU-E and a corresponding 94% decrease in the number of CD71++gly A- cells, thereby maintaining the relationship between CD71++gly A- cells and BFU-E. Therefore, flow cytometric analysis was found to be useful in assessing erythroid development, and this approach may be used to develop flow cytometric assays for other populations of interest in hematopoietic cell cultures.

Antigens, CD↗
PubMed1995

Magnetic resonance imaging of endocrine tumours of the pancreas.

Seven patients who had functioning or non-functioning endocrine pancreatic tumours were investigated by magnetic resonance imaging. Combinations of fat suppressed T1 weighted spin echo and gradient recalled echo (n = 7), T2 weighted spin echo (n = 3) and gadolinium diethylamine triamine pentaacetic acid (Gd-DTPA) enhanced fat suppressed T1 images were acquired. Magnetic resonance imaging detected five of seven tumours prospectively (three of which were smaller than 10 mm) and a further 10 mm tumour retrospectively. Tumours were low signal on T1 weighted images and showed enhancement after Gd-DTPA. On T2 weighted images one tumour was hyperintense, and two were isointense with normal pancreas. Computed tomography, transabdominal ultrasound and angiography were performed in six patients but detected only one tumour each. Intraoperative palpation and ultrasound detected all tumours. If pre-operative imaging is required magnetic resonance imaging is the technique of choice to detect small endocrine pancreatic tumours.

Adult↗
PubMed1992

Experimental in vivo generation of intertypic recombinant strains of HSV in the mouse.

The primary replication of one strain of HSV was generally unaffected by the simultaneous inoculation of another strain either at the same site or at a different site within the same dermatome. Exceptions to this were the result of the generation of intertypic recombinants which were readily isolated only from sensory ganglia 5 and 6 days after inoculation with a mixture of HSV-1 and HSV-2 and from explant culture of the resultant latently infected ganglia. By restriction enzyme analysis the majority of the recombinant strains from primary infection were characterized as HSV 1; all those from latently infected ganglia were characterized as type 2.

Animals↗
PubMed1991

Clinico-radiological correlates in rupture of the major airways.

The plain film appearances of 17 patients with trauma to the major airways were reviewed and correlated with the findings at thoracotomy, bronchoscopy or post-mortem. Predictable radiographic patterns of air leak were discovered which related to the surgical anatomy of the rupture. Airway interruption was seen in two of three patients with laryngeal transection, all showing gross deep and superficial cervico-facial emphysema. Massive mediastinal and deep cervical emphysema without pneumothorax were striking features of tracheal injury. In patients with bronchial rupture all had ipsilateral pneumothorax and most had associated pneumomediastinum, the degree of each component relating to the site of rupture. Only two patients had tension pneumothoraces. These features alone, however, are non-specific and only two of seven patients with bronchial injury showed specific signs of rupture (a fallen lung). An understanding of the mechanisms of injury to the major airways and the predictable resultant patterns of air leak should ensure that such lesions are not overlooked in patients who will usually have sustained multisystem trauma.

Adolescent↗
PubMed1991

An in vivo animal model of gene therapy for leukocyte adhesion deficiency.

Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function that is caused by defects in the CD18 gene and is associated with diminished cell surface expression of CD11/CD18 proteins. We have developed an in vivo model for gene therapy of LAD. Recombinant retroviruses were used to transduce a functional human CD18 gene into murine bone marrow cells which were transplanted into lethally irradiated syngeneic recipients. A reliable flow cytometric assay for human CD18 in transplant recipients was developed based on: (a) the availability of human specific CD18 monoclonal antibodies and (b) the observation that human CD18 can form chimeric heterodimers with murine CD11a on the cell surface. Human CD18 was detected on leukocytes in a substantial number of transplant recipients for at least 6 mo suggesting that the gene had been transduced into stem cells. Expression was demonstrated in several lineages of a variety of hematopoietic tissues, but was consistently highest and most frequent in granulocytes. Murine granulocytes demonstrated appropriate posttranscriptional regulation of human CD18 in response to activation of protein kinase C. No apparent untoward effects of human CD18 expression were noted in transplant recipients. These studies suggest a specific strategy for LAD gene therapy that may be effective and safe.

Animals↗
PubMed1990

Correction of CD18-deficient lymphocytes by retrovirus-mediated gene transfer.

Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function caused by derangements in CD18 expression. The genetic and functional abnormalities in a lymphocyte cell line from a patient with LAD have been corrected by retrovirus-mediated transduction of a functional CD18 gene. Lymphocytes from patients with LAD were exposed to CD18-expressing retrovirus and enriched for cells that express CD11a and CD18 (LFA-1) on the cell surface. Molecular and functional analyses of these cells revealed (i) one copy of proviral sequence per cell, (ii) viral-directed CD18 RNA that exceeded normal endogenous levels, (iii) normal quantities of CD11a and CD18 protein on the cell surface, and (iv) reconstitution of LFA-1-dependent adhesive function.

Animals↗
PubMed1990

Heterotypic and homotypic re-inoculation of mice already latently infected with herpes simplex virus type 1.

Mice were infected at 4 weeks of age with a type 1 strain of herpes simplex virus (HSV) and re-infected 4 weeks later with either a type 1 or a type 2 strain of HSV. The virus used for first infection could be distinguished from that used later since it was resistant to phosphonoformic acid and formed syncytial plaques. Sites used for the second inoculation were as follows: at the site of primary infection, at a different site within the same dermatome or in the equivalent dermatome on the opposite side (also called "remote" site). Re-infection caused no detectable reactivation of the latent PFA resistant virus. After re-infection with a homotypic virus replication of the re-infecting virus was limited to the inoculation site. However after heterotypic re-infection the type 2 strain was occasionally isolated from the ganglia. Previous infection with the PFA resistant type 1 strain clearly reduced the ability of the homotypic or heterotypic strains to establish a latent infection. However, in a few animals ganglia were found to be latently infected with virus from both the first and second inoculations. Analysis of the results suggests that resistance to the establishment of a second latent infection in a ganglion is determined by the general immunity of the animal rather than "immunity" of the latently infected ganglion itself.

Animals↗
PubMed1990

Modulation of the cytotoxic mechanism of 6-thioguanine by 4-amino-5-imidazolecarboxamide.

Previous evidence has indicated that either purine starvation or incorporation into DNA may be the dominant biochemical effect of the antileukemic agent 6-thioguanine (TG), depending on exposure conditions. Furthermore, it has been suggested that the paradoxical decrease in TG-induced cytotoxicity at high drug concentrations may be due to an antagonistic interaction between these two mechanisms, in which purine starvation inhibits DNA synthesis and, therefore, incorporation of TG into DNA. In this report we test the hypothesis that by concurrent treatment of L1210 cells with TG and the purine precursor 4-amino-5-imidazolecarboxamide (AIC) it is possible to alleviate DNA synthesis inhibition caused by high concentrations of TG, thus enhancing TG incorporation into DNA and TG-induced cell kill. Both the cytotoxic and cytokinetic results presented support this hypothesis. However, gross incorporation of TG into DNA was not increased by AIC under conditions in which a significant enhancement of cytotoxicity (i.e., 1 log) was observed. These findings suggest that the potentiating effect of AIC may be most prominent on the subpopulation of cells that are resistant to treatment with TG alone, and they demonstrate that the cytotoxic effects of TG treatments are more accurately reflected by observing specific cytokinetic changes (delayed late S/G2 arrest) than by measuring the average extent of TG incorporation into DNA within a given population. Finally, we propose that it may be possible to select conditions for administration of TG that favor one or the other cytotoxic mechanism, depending on whether the clinical objective is induction of remission (where rapid cell lysis due to purine starvation would be desired) or eradication of subclinical disease during remission (where proliferation-dependent cytotoxicity due to DNA incorporation should be more effective.

Aminoimidazole Carboxamide↗
PubMed1989

Prediction of thioguanine-induced cytotoxicity by dual-parameter flow cytometric analysis.

A method is presented for the quantitative analysis of delayed cytokinetic effects resulting from the treatment of L1210 cells with 6-thioguanine (TG). By using dual-parameter (DNA/protein) flow cytometry, we could observe the accumulation of late S/G2/M cells with abnormally high green fluorescence (i.e., protein content), indicative of unbalanced growth. The use of mitotic cells from a pseudotetraploid line (HT29) as external markers for both red and green fluorescence facilitated highly reproducible measurement of the mean green fluorescence (GFLmean) of the arrested late S/G2/M population. We found that the dose dependence of the observed GFLmean values followed the same unusual biphasic pattern as did cytotoxicity in this cell line, indicating that this parameter might be a suitable means of predicting TG-induced toxicity in vivo. We propose that the low background expected for this kind of measurement would make it particularly appropriate for the analysis of clinical specimens (e.g., mononuclear bone marrow cells) from leukemic patients receiving thiopurines, to monitor (and, hopefully, predict) their response to treatment.

Algorithms↗
PubMed1989

Response of human HT-29 colorectal tumor cells to extended exposure to bromodeoxyuridine.

Effects of the extended exposure of a human colorectal tumor-cell line (HT-29) to bromodeoxyuridine (BrdUrd) were studied in anticipation of the clinical use of that agent to treat colorectal cancer, particularly as a regionally delivered radiosensitizer. We found that 72-h exposure to a concentration of BrdUrd that is estimated to be locally maintained in the liver (100 microM) was significantly cytotoxic with a 3-log reduction in survival. As measured by GC/MS-SIM method, incorporation of BrdUrd into DNA followed an unexpected time course in that continuous exposure to 10 microM BrdUrd resulted in maximal incorporation at 3 days, after which the extent of incorporated analog fell significantly (despite daily changes of the medium). This finding was apparently due to a greater rate of loss of BrdUrd from the medium at later time points. Flow cytometric analysis using an anti-BrdUrd antibody (IU-4) revealed that antibody binding also peaked and fell off with time. However, at exposure times of greater than 24 h, the timing and extent of this decline were significantly different than had been indicated by the GC/MS method. These results indicate that the quantitative relationship between antibody staining and BrdUrd incorporation changes as drug-exposure time increases and that quantitative studies of anti-BrdUrd antibody binding must be interpreted with caution, especially when extended drug-treatment protocols have been used.

Bromodeoxyuridine↗
PubMed1989

Early abdominal complications of intestinal surgery: the radiologist's role in management.

Abdominal complications of intestinal surgery are an important cause of postoperative morbidity and mortality. We define early complications as those occurring within the first 30 days after surgery. The radiological contribution towards prompt and accurate diagnosis of common complications is discussed and the radiologist's role in non-operative management is outlined.

Abscess↗