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Biomedical subjects

S Coleman

Publications and source records attributed to S Coleman.

At least 37 records · Page 2Linked to original sources
PubMed1998

Entrapment and transection of the median nerve associated with greenstick fractures of the forearm: case report and review of the literature.

OBJECTIVE: To report an unusual neurologic complication associated with greenstick fractures of the forearm. METHODS: Near-complete transection of the median nerve associated with greenstick fractures of the shaft of the left radius and ulna in a 13-year-old boy is described. The results of treatment are reported in detail. CONCLUSION: Significant median nerve injury may coexist with apparently benign, closed greenstick fractures of the forearm.

Adolescent↗
PubMed1997

Chronic myeloid leukemia as an immunological target.

Various clinical observations have implicated T cells in the control of chronic myeloid leukemia (CML). These observations have in recent years been supported by laboratory results indicating the presence of CML-specific T cells in the lymphocyte repertoire of both normal healthy individuals and disease-bearing patients. Both MHC-unrestricted and MHC-restricted immune effector mechanisms are involved. Donor lymphocyte infusion has produced encouraging GvL effects. However, future adoptive immunotherapy may depend on the isolation and generation of leukemia-specific T cells. Although many proteins may potentially act as leukemia antigens in CML for MHC-restricted cytotoxicity, the bcr-abl fusion protein has been most extensively investigated. There is now much evidence to suggest that the bcr-abl junctional peptides are capable of eliciting both CD4 and CD8 responses in normal healthy donors and CML patients. Furthermore, the T-cell lines generated react with autologous or HLA-matched fresh CML cells, suggesting that the bcr-abl fusion protein can be processed in vivo so that the joining segment is bound to HLA molecules in a configuration and concentration similar to those of the immunizing peptide for antigen recognition by the antigen-specific T-cell receptor. These results also indicate that the bcr-abl junctional peptides may be used for immunotherapy of CML. Other strategies available for immunotherapy of CML include immunologically or genetically manipulated donor T-cell infusion, the use of cytokines, adoptive immunotherapy with leukemia-reactive T-cells expanded ex vivo, and immune gene therapy. Novel and rational immunotherapy may therefore play an important adjuvant role in future in the management of patients with CML.

CD4-Positive T-Lymphocytes↗
PubMed1997

Cyclosporin A/alpha interferon-induced autologous graft-versus-host disease following peripheral blood stem cell transplant for chronic myeloid leukaemia: a clinico-pathological study.

Autologous GVHD was induced using CsA and alpha-IFN in a patient undergoing autologous PBSCT for accelerated phase CML. We demonstrated that the autologous mixed lymphocyte reactions were extremely sensitive and specific for the detection of the GVHD when compared to skin biopsy. The resultant autologous GVHD was associated with an in vitro GVL effect, suggesting a potential clinical benefit of this therapeutic manoeuvre. The post-PBSCT period was associated with an improvement in normal haemopoiesis and reduction in the proportion of blood cells expressing the Philadelphia chromosome.

Antineoplastic Agents↗
PubMed1997

Cytokine enhancement of immunogenicity in chronic myeloid leukaemia.

Various clinical and laboratory observations suggest that the leukaemia cells in chronic myeloid leukaemia (CML) are potentially immunogenic. Whilst the ability of the leukaemia cells to elicit an anti-leukaemic immune response in the allogeneic setting is established, it remains unclear why such anti-leukaemic response does not occur in vivo in the autologous setting. We previously demonstrated the presence of leukaemia-reactive T cells in a patient with CML. However, we found that the T cells were normally anergic unless pre-incubated in vitro in high-dose recombinant interleukin-2. We speculated that the T cell anergy was the result of a lack of the appropriate immune costimulatory molecules on the leukaemia cell surface. In this study, we confirm the absence of immune costimulatory molecules, CD80 (B7-1) and CD86 (B7-2), on leukaemia cells and demonstrated that these costimulatory molecules on the leukaemia cells can be upregulated by a combination of GM-CSF and IL-4. There was an associated restoration of leukaemia cell immunogenicity to autologous T cells in mixed lymphocyte leukaemia reactions, suggesting a possible enhancement of anti-leukaemic reaction. More importantly, T cells primed with 'activated' leukaemia cells were able to recognise fresh cytokine-naive leukaemia cells. Furthermore, leukaemia cells expressing the dendritic cell marker, CD1a, were also generated. Our findings therefore suggest the opportunity in future to use these combination cytokines in vivo or these leukaemia cells which have been activated in vitro for leukaemia immunotherapy.

Cytokines↗
PubMed1997

Molecular analysis of T cell receptor beta variability in a patient with orofacial granulomatosis.

BACKGROUND: Orofacial granulomatosis (OFG) is a rare chronic inflammatory disorder of unknown causation and is characterised histologically by non-caseating granulomas and aggregates of small lymphocytes. The molecular nature of these T cells is, however, unclear. AIMS: To determine the T cell receptor (TCR) V beta gene usage of the T cell infiltrate associated with the primary lesions in a patient with OFG. METHODS: A molecular method involving reverse transcriptase (RT)-polymerase chain reaction (PCR), DNA cloning, single strand conformation polymorphism (SSCP), length analysis, and nucleotide sequencing was used. RESULTS: Compared with peripheral blood lymphocytes from the same patient, notably restricted TCRV beta gene usage was observed in the T cell infiltrate. Only three of the 24 major TCRV beta gene families were represented in the repertoire. There was preferential usage of the V beta 6 gene. In addition, more than 20% of the V beta 6 TCR transcripts exhibited an identical unique V-D-J junctional sequence, suggesting a local antigen driven V beta 6 T cell clonal expansion in vivo, a phenomenon not observed in normal oral mucosa. CONCLUSIONS: The TCRV beta repertoire of T cells associated with OFG is restricted. It is also associated with a local T cell clonal expansion. The results, therefore, provide a new perspective on the immunopathology of OFG.

Amino Acid Sequence↗
PubMed1997

Gas chromatographic-mass spectrometric determination of benzo[a]pyrene and chrysene diol epoxide globin adducts in humans.

The efficacy of a newly developed gas chromatography-negative ion chemical ionization-mass spectrometry-selected ion monitoring (GC-NICI-MS-SIM) assay for measuring globin adducts of benzo[a]pyrene (B[a]P) and chrysene diol epoxides in human was evaluated. In this pilot study, smokers and nonsmokers were selected as exposed and nonexposed groups. Using [2H12]r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyren e ([2H12]trans,anti-B[a]P-tetraol) as an internal standard, B[a]P-tetraols released from globin after hydrolysis and derivatization were quantified by GC-NICI-MS-SIM. Levels of trans-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrochrysene (chrysene-DE)-globin adducts were estimated by assuming that the recovery and the MS response of the perdeuterated B[a]P-tetraol internal standard reflected the recovery and MS response of chrysene tetraols. The assay was found to be reproducible and sensitive enough to detect both analytes in all samples. The mean levels of B[a]P-tetraols released from the corresponding benzo[a]pyrene diol epoxide (BPDE) globin adducts in smokers were significantly higher than those in nonsmokers, i.e., 2.6 +/- 0.6 SE fmol/mg globin (ranging from 1.2 to 7.8 fmol/mg globin) in smokers and 0.97 +/- 0.05 SE fmol/mg globin (ranging from 0.7 to 1.3 fmol/mg globin) in nonsmokers (P < 0.01). Interestingly, estimated levels of chrysene-DE-globin adducts in the same subjects were about two orders of magnitude higher than those of the globin adducts of BPDE. The mean of the chrysene-DE adducts in smokers was estimated to be 310 +/- 30 SE fmol/mg globin (ranging from 190 to 460 fmol/mg globin) and that in nonsmokers was 250 +/- 25 SE fmol/mg globin (ranging from 110 to 380 fmol/mg). Although the estimated mean of chrysene-DE adducts with globin in smokers appeared to be about 25% higher than in nonsmokers, the difference was not significant (P = 0.06). The results of this study demonstrate the feasibility of the GC-NICI-MS-SIM method for measurement of BPDE globin adducts in humans.

Benzopyrenes↗
PubMed1996

Defining and implementing a 'no lifting' standard.

Following the launch this spring of the RCN's campaign to reduce injuries from manual lifting of patients, this article describes the main policies and guidelines relating to lifting and handling, and tells how these were used to develop and implement a 'no lifting' standard on an elderly care ward.

Back Pain↗
PubMed1996

Antibody response to measles-mumps-rubella vaccine of children with mild illness at the time of vaccination.

OBJECTIVE: To examine the response to measles-mumps-rubella (MMR) vaccine among children with and without mild illness. DESIGN: Prospective cohort. PARTICIPANTS: A total of 386 children aged 15 to 23 months. MAIN OUTCOME MEASURES: Seroconversion rates to measles, mumps, and rubella in ill and well children. SETTING: Six public health immunization clinics in two counties in the greater metropolitan Atlanta, Ga, area from February 1992 to April 1993. RESULTS: Acute upper respiratory tract infection, otitis media, and diarrhea were observed in 128 (33%), 41 (11%), and 13 (3%) of the children (groups are not mutually exclusive); 157 children had one of these mild illnesses and 229 were well. Overall seroconversion rates were 98% for measles, 83% for mumps, and 98% for rubella antigens. Measles seroconversion rates for ill children compared with well children, respectively, were as follows: upper respiratory tract infection, 99% vs 97%; mild fever, 98% vs 97%; otitis media, 98% vs 98%; diarrhea, 100% vs 98%; and any mild illness, 99% vs 97%. Estimates of the magnitude of antibody response to measles, mumps, and rubella antigens were the same for children with and without mild illness. There was no association of mild illness with increased rates and severity of adverse events reported in the 2 weeks after vaccination. CONCLUSIONS: Vaccinating children who present with mild illnesses with MMR vaccine is a safe and efficacious practice. These results support recommendations of the Advisory Committee on Immunization Practices and the American Academy of Pediatrics.

Antibodies, Viral↗
PubMed1996

T cell receptor Vbeta repertoire of tumour-infiltrating lymphocytes in oral squamous-cell carcinoma.

Oral squamous cell carcinoma (OSCC) are frequently infiltrated by tumour infiltrating lymphocytes (TILs) which may demonstrate specific anti-tumour cytotoxicity. We have used a panel of family-specific primers in reverse-transcriptase (RT)-polymerase chain reactions (PCR) to determine the TCR Vbeta repertoire of TILs in the primary and metastatic tumours in patients with OSCC. We observed a diverse and heterogenous usage of TCR Vbeta genes by TILs in the primary tumours, a scenario not unlike normal oral mucosal lymphocytes. In one patient with a longstanding history of OSCC, the repertoire was restricted. Restricted TCR Vbeta gene usage also occurred in TILs of metastatic tumours. Within individual patients, discrepancies of TCR Vbeta gene usage were also observed between TILs in the primary OSCC and those in metastatic lymph nodes. Work is ongoing to determine the clonality and functional significance of these TILs.

Biopsy↗
PubMed1996

Detection of DNA and globin adducts of polynuclear aromatic hydrocarbon diol epoxides by gas chromatography-mass spectrometry and -3H-CH3I postlabeling of released tetraols.

Gas chromatography-negative ion chemical ionization mass spectrometry--selected ion monitoring (GC-NICI-MS-SIM) was employed to detect tetramethyl ether derivatives of tetraols formed upon hydrolysis of DNA and globin adducts derived from diol epoxides of benzo[a]-pyrene (BP) and other polynuclear aromatic hydrocarbons (PAH). The tetramethyl ether derivatives could also be detected by [3H]CH3I postlabeling. The methodology involves the following steps: (1) isolation of DNA or globin; (2) mild acid hydrolysis under vacuum; (3) isolation of the resulting tetraols and derivatization to the corresponding tetramethyl ethers using methyl sulfinyl carbanion and unlabeled or 3H-labeled CH3I; (4) analysis by GC-NICI-MS-SIM or HPLC with radioflow detection. The optimum conditions for hydrolysis of adducts and derivatization of the resulting tetraols as well as the feasibility of this approach for detecting PAH adducts in mice and humans were explored. Using the set of four BP-tetraols that can be formed upon hydrolysis of adducts formed from r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) or r-7,t-8-dihydroxy-c-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (syn-BPDE) as models, the stability of the tetraols under the hydrolysis conditions was investigated. Adducts derived from anti-BPDE yield predominantly the stable r-7,t-8,9-c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-anti-BP-tetraol), while adducts derived from syn-BPDE released cis-syn-BP-tetraol as a major hydrolysis product. Hydrolysis under vacuum significantly increased the recovery of tetraols. Conditions for derivatization of the BP-tetraols as well as tetraols derived from several other PAH anti-diol epoxides were investigated. Tetramethyl ethers proved to be superior derivatives that were stable, easy to prepare in high yields, and detectable with high sensitivity by GC-NICI-MS-SIM (1-50 fmol per injection). Alternatively, these derivatives could be detected by HPLC with radioflow detection if [3H]CH3I were employed for derivatization. The methodology was tested by comparing levels of DNA and globin adducts in mice treated with either unlabeled or 3H-labeled BP. Good agreement was obtained among the GC-NICI-MS-SIM, [3H]CH3I postlabeling, and conventional radiometric methods. Moreover, analysis of human hemoglobin by GC-NICI-MS-SIM resulted in detection of adducts derived from anti-BPDE and r-1,t-2-dihydroxy-t-3,4-epoxy-1,2,3,4-tetrahydrochrysene. The results of this study demonstrate that GC-NICI-MS-SIM of tetramethyl ethers of tetraols formed by hydrolysis of PAH diol epoxide DNA and globin adducts is a promising approach for detection and quantitation of adducts derived from a broad range of PAH.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1996

Randomized, controlled phase I/II, trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients.

Delavirdine mesylate (DLV) is a potent nonnucleoside reverse transcriptase inhibitor with activity specific for human immunodeficiency virus type 1. In the present phase I/II study we evaluated the safety, toxicity, pharmacokinetics, and antiretroviral activities of two-drug and three-drug combinations of DLV and conventional doses of nucleoside analogs compared with those of both DLV monotherapy and two-drug nucleoside analog therapy. A total of 85 human immunodeficiency virus type 1 infected patients with CD4 counts of 100 to 300 cells per mm3 were enrolled in two periods: in the first period patients were randomized to receive either zidovudine (ZDV) plus didanosine (group 1) or ZDV plus didanosine plus escalating doses (400 to 1,200 mg/day) of DLV (group 2). In the second period, patients were randomized to receive either 1,200 mg of DLV alone per day (group 3) or ZDV plus 1,200 mg of DLV per day (group 4). DLV demonstrated good oral bioavailability at all five doses tested. The major toxicity was a transient mild rash which appeared in 44% of all DLV recipients. Overall, group 2 patients demonstrated more sustained improvements in CD4 counts, percent CD4 cells, branched DNA levels, p24 antigen levels, and virus titers in plasma than group 1, 3, or 4 patients. The magnitude of the response correlated with the intensity of prior nucleoside analog treatment, the non-syncytium-inducing or syncytium-inducing viral phenotype at baseline, and the presence of a wild-type codon at amino acid position 215 in the baseline reverse transcriptase genotype. Despite a transient rash, DLV therapy was well tolerated. Combination therapy with DLV and nucleoside analogs appears promising, with the three-drug combination appearing to be more potent that either two-drug combinations or monotherapy.

Adult↗
PubMed1996

Autologous MHC-dependent leukaemia-reactive T lymphocytes in a patient with chronic myeloid leukaemia.

We have investigated the presence of T cells capable of recognizing autologous leukaemia cells in a patient with CML. We demonstrated that these cells were anergic to the leukaemia cells. They were estimated to be present at a frequency of 1:4000 T cells in the peripheral blood. However, following incubation with high dose rIL-2, these effector cells were able to proliferate, secrete TH1 cytokines and lyse target cells upon challenging with fresh autologous leukaemia cells. Both CD4 and CD8 T cells were involved in the proliferative responses. Moreover, the immune response was blocked by monomorphic anti-HLA antibodies, suggesting that the MHC molecules are needed by the T cells for leukaemia cell/antigen recognition. This work therefore indicates a potential reservoir of effector cells in CML patients which may be exploited for the modulation of leukaemia cell growth. It also provides evidence for a distinct T cell population capable of mediating GVL responses.

Autoimmunity↗
PubMed1995

A Drosophila male accessory gland protein that is a member of the serpin superfamily of proteinase inhibitors is transferred to females during mating.

Accessory gland peptide 76A, (Acp76A), belongs to the serpin superfamily of proteins (serine protease inhibitors). Acp76A is a secreted protein synthesized only in the Drosophila melanogaster adult male accessory gland. Accumulation of the protein in males is first detected with polyclonal antibodies at 1 day after eclosion. The level of the protein in virgin males reaches a peak 5-8 days post-eclosion, and remains constant for at least 20 days. Upon mating the amount of Acp76A in males drops dramatically, but recovers by 24 h after mating. Immediately after mating the Acp76A is found in the female uterus. By 6 h after mating the amount of Acp76A detected in females is drastically reduced.

Animals↗
PubMed1995

Abnormal TCR V beta repertoire in patients with chronic myeloid leukaemia.

We have used 25 sets of oligonucleotide primers specific for the 24 known major human T-cell receptor (TCR) V beta families in polymerase chain reactions to analyse the T-cell repertoire of the peripheral blood in seven patients with chronic myeloid leukaemia (CML). In contrast to normal healthy individuals, all seven patients exhibited variable degrees of TCR V beta-specific T-cell deletion, ranging from two to eight of the 24 major families. T cells bearing V beta 17 and 8 were most commonly deleted. These results suggest a superantigen effect associated with CML. The patterns of deletion did not appear to correlate with either of the two bcr-abl transcripts. The reason and aetiological agent responsible for the T-cell deletion remain speculative. Further work is ongoing to characterize this phenomenon in animal models and patients with CML.

Base Sequence↗
PubMed1995

All trans retinoic acid enhances human LAK activity.

All trans retinoic acid has various effects on normal and malignant cells. Lymphokine-activated killer (LAK) activity can be derived from T lymphocytes and natural killer cells. This study shows that all trans retinoic acid significantly enhances this activity by increasing production of tumour necrosis factor and gamma interferon, which results in enhanced expression of the p55 part of the interleukin 2 receptor. This effect is dependent on the concentration of all trans retinoic acid and the length of time of culture.

Cells, Cultured↗
PubMed1995

Adenosine A2 receptors reverse ischemia-reperfusion lung injury independent of beta-receptors.

To evaluate the adenosine systems ability to reverse the endothelial damage produced by ischemia and reperfusion (I/R), we studied several different selective adenosine-receptor agonists and antagonists, a protein kinase A inhibitor, and a beta-adrenoreceptor antagonist in isolated buffer-perfused rat lungs. I/R (45 min/105 min) produced a sixfold increase in endothelial permeability as measured by the capillary filtration coefficient. Both a selective A2-receptor agonist (CGS-21680, 300 nM) and a beta-receptor agonist (isoproterenol, 10 microM) reversed the increased microvascular permeability. A nonselective adenosine-receptor antagonist (SPT, 20 microM) and a selective A1-receptor antagonist (DPCPX, 10 nM) had no effect on increased microvascular permeability. Also, isoproterenol and CGS-21680 reversed the damage being introduced after a selective A1-receptor agonist (CCPA, 100 nM). The nonspecific adenosine A1- and A2-receptor agonist NECA (12 nM) appeared to desensitize the A2 receptors and a protein kinase A inhibitor, adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS, 100 microM), blocked the reversal of endothelial damage by isoproterenol or A2-receptor agonist. Propranolol (100 microM) blocked the effect of isoproterenol but not the effect of CGS-21680. From this study we conclude that A2-receptor activation reverses endothelial damage associated with I/R by a mechanism independent of beta-receptors or Gi protein. However, a protein kinase A-3',5',-cyclic adenosine monophosphate pathway is activated by both the adenosine systems and beta-receptor activation.

Adenosine↗
PubMed1995

In vitro LAK (lymphokine activated killer) activity following autologous peripheral blood stem cell is significantly greater than that following autologous bone marrow and allogeneic bone marrow transplantation.

LAK activity is known to increase following autologous and allogeneic bone marrow transplant and peripheral blood stem cell transplant (PBSCT). The aim of this study was to directly compare the 3 types of transplant and the LAK activity generated. LAK activity following PBSCT is significantly greater than that following autologous bone marrow transplantation and even allogeneic transplantation up to 8 weeks. The type of killer cells generated is similar for the different types of transplants, with most killing activity following PBSCT due to CD56+ cells, though CD3+ cells also contribute. This study would suggest that attempts to augment the graft-versus-leukaemia effect is more likely to be successful following PBSCT than autologous bone marrow transplantation.

Adolescent↗