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Biomedical subjects

P L Martin

Publications and source records attributed to P L Martin.

At least 19 recordsLinked to original sources

Thermal stability of the thermoluminescence trap structure of bentonite.

This work reports about the thermal stability of the blue thermoluminescence (TL) of a well-characterised natural bentonite from Almeria (Spain). The main interest of this clay, mainly composed of montmorillonite, is because of its application in the field of high-level radioactive waste (HLW) repository in deep-lying rocks. As observed in other aluminosilicates, bentonite exhibits a very complex structure of the emission spectra based on a wide broad maximum peaked at approximately 265 degrees C that can be associated to physico-chemical processes such as dehydroxylation processes, consecutive breaking linking of bonds, formation of hydrolysed ions and redox reactions. The thermal stability tests performed at different temperatures confirm a continuum in the distribution of traps. Hence, the glow curve analysis methods commonly used for synthetic materials based on single discrete traps cannot be applied for this material and the kinetic parameters were fitted assuming an exponential distribution of trapped electrons.

Bentonite↗

Incorporation of bovine bone marrow stromal cells into porcine foetal tissues after xenotransplantation.

Bovine bone marrow stromal cells (BMSCs) were injected into the liver of foetal pigs at about 40 days of gestation to test whether these cells could populate developing tissue, and if so, which ones. Approximately 40 days after injection, the foetuses were harvested and tissue sections from many areas of the body were analysed for the presence of bovine cells using two different methods. First, using PCR, bovine repetitive DNA was found to be present in DNA extracted from foetal pig tissues. Secondly, using oligonucleotide primed in situ synthesis (PRINS), the in situ presence of bovine cells was found within porcine tissue sections. PRINS-labelled cells were found within cartilage, perichondrium, connective tissue and smooth muscle. These data suggest that bovine BMSCs integrate throughout the foetal pig.

Animals↗

Human herpesvirus 6 limbic encephalitis after stem cell transplantation.

Central nervous system complications are common in stem cell transplant recipients, but selective involvement of the medial temporal area is unusual. The 5 patients reported here presented after stem cell transplantation with increased hippocampal T2 signal on magnetic resonance imaging and increased hippocampal glucose uptake on [F-18]fluorodeoxyglucose-positron emission tomography (FDG-PET) associated with short-term memory loss, insomnia, and temporal lobe electrographic seizure activity. The initial scalp electroencephalograms (EEGs) failed to detect seizure activity in these patients, although the memory dysfunction along with the magnetic resonance imaging and FDG-PET findings suggested subcortical seizure activity. However, extended EEG monitoring revealed repetitive temporal lobe electrographic seizure activity. Follow-up MRIs in 2 patients and postmortem findings on 1 patient suggested that hippocampal sclerosis had developed following the clinical syndrome. Cerebrospinal fluid studies revealed the presence of human herpesvirus 6, variant B, DNA in all of 3 patients who had lumbar punctures. Immunohistochemical staining for the P41 and P101 human herpesvirus 6 protein antigens showed numerous immunoreactive astrocytes and neurons in the hippocampus of 1 of the patients who died from other causes. Because of its subtle clinical presentation, this syndrome may be underrecognized, but can be diagnosed with appropriate magnetic resonance imaging techniques, EEG monitoring, and cerebrospinal fluid viral studies.

Adolescent↗

Low incidence of Epstein-Barr virus-associated posttransplantation lymphoproliferative disorders in 272 unrelated-donor umbilical cord blood transplant recipients.

Umbilical cord blood (UCB) is being increasingly used for transplantation, but the ability of neonatal T cells to regulate Epstein-Barr virus (EBV)-associated lymphoproliferation is unknown. Because UCB transplantation (UCBT) is associated with a relatively low infused dose of donor T cells, frequent donor-recipient HLA disparity, and use of antithymocyte globulin during conditioning, we hypothesized that the risk of EBV-associated posttransplantation lymphoproliferative disorders (EVB-PTLD) after UCBT may be increased. To investigate the incidence of EBV-PTLD after UCBT, we analyzed 272 unrelated-donor UCBTs performed from August 1993 to December 1999 at Duke University Medical Center and the University of Minnesota. Five cases of EBV-PTLD were identified, with a cumulative incidence of 2% (95% confidence interval, 0.3%-3.7%) at 2 years. EBV-PTLD affected UCB recipients aged 1 to 49 years (median, 8 years), with 4 patients undergoing transplantation for leukemia and 1 for immunodeficiency. Patients received UCB grafts that were HLA matched (n = 1) or mismatched at 1 (n = 1) or 2 (n = 3) HLA loci. Diagnoses occurred at 4 to 14 months (median, 6 months) after UCBT, with 4 of 5 patients having preceding grade II to IV acute graft-versus-host disease and 1 being diagnosed at autopsy. Treatment of 4 patients consisted of withdrawal of immunosuppressive treatment and administration of rituximab, with 2 of 4 patients responding. Thus, the incidence of EBV-PTLD after unrelated-donor UCBT appears similar to that observed after transplantation using unrelated bone marrow (BM) and compares favorably with unrelated-donor T-cell-depleted BM transplantation. Because adoptive immunotherapy with donor lymphocytes is not an available option for recipients of unrelated-donor UCBT, new therapeutic strategies are needed, and rituximab appears promising.

Adolescent↗

Xenotransplantation of bovine bone marrow stromal cells into pig fetuses: incorporation into skeletal muscle.

Bone marrow stromal cells are multipotent and have been shown to differentiate into a wide variety of mesenchymal cell types in vivo. In this study we tested the ability of bovine bone marrow stromal cells to contribute to the development of porcine skeletal muscle tissue. Fetal pigs were injected early in gestation with bone marrow stem cells originating from slaughtered steers. After approximately forty days of development the fetuses were harvested and sections of their skeletal muscle were analyzed for the presence of bovine cells. PCR was used to detect bovine DNA present in DNA extracted from the fetal pig skeletal muscle. We also used a PRINS (Oligonucleotide Primed In- Situ Synthesis) protocol to confirm the presence of bovine cells within the porcine skeletal muscle tissue sections. The results of both assays indicate that bovine bone marrow stromal cells can participate in the development of porcine skeletal muscle. This study helps to demonstrate the potential that bone marrow stromal cells have to contribute to advances in animal biotechnology and medicine.

Animals↗

Graft-versus-leukemia-induced complete remission following unrelated umbilical cord blood transplantation for acute leukemia.

A 15-year-old female received an unrelated three of six HLA antigen matched umbilical cord blood (UCB) transplant for refractory, relapsed T-cell ALL. Conditioning consisted of TBI, melphalan, and anti-thymocyte globulin (ATG), with cyclosporin A (CsA) and solumedrol for GVHD prophylaxis. She engrafted and a day 34 bone marrow aspirate showed 100% donor cells and no evidence of leukemia. The post-transplant course was complicated by mild grade I acute GVHD involving skin, and limited chronic GVHD of the gut which resolved with the addition of 1 mg/kg/day of steroids to her CsA prophylaxis. One hundred and ninety days after transplantation the patient developed pancytopenia and was subsequently found to have a leukemic relapse. Immunosuppression was discontinued and she was started on G-CSF and erythropoietin. Moderate skin and gut GVHD developed which was treated with both topical and low-dose oral steroids. Over the next few weeks she became transfusion independent and a follow-up bone marrow aspirate showed complete remission. She continued in complete remission for 4 months, at which time localized leukemic relapse was found in a soft tissue breast mass in spite of continued bone marrow remission. While the patient ultimately died of progressive disease, this case demonstrates that mismatched UCB in conjunction with G-CSF is capable of generating a GVL effect that can induce a complete remission.

Adolescent↗

Adenosine agonists for the prevention of restenosis?

Balloon angioplasty involves the simultaneous activation of platelets and neutrophils. Activated platelets release mitogenic substances that cause smooth muscle cell proliferation and thereby contribute to restenosis. Activated neutrophils activate platelets and activated platelets activate neutrophils. Therefore the simultaneous activation of both cell types may be responsible for the exaggerated repair mechanisms resulting in restenosis of coronary blood vessels. Adenosine inhibits neutrophil activation, platelet activation and smooth muscle cell proliferation and stimulates endothelial cell proliferation predominantly through activation of A2A-receptors. Adenosine and A2A-selective agonists may be useful in the prevention of restenosis following balloon angioplasty.

Journal Article↗

Toxicity, pharmacology and feasibility of administration of PEG-L-asparaginase as consolidation therapy in patients undergoing bone marrow transplantation for acute lymphoblastic leukemia.

We attempted to administer PEG-L-asparaginase (PEG-L-A) following hematologic recovery to 38 patients undergoing autologous or allogeneic marrow transplantation for acute lymphoblastic leukemia (ALL). Twenty-four patients (12 of 22 receiving allogeneic and 12 of 16 receiving autologous transplants) received between one and 12 doses of PEG-L-A, including nine who completed the planned 12 doses of therapy. The toxicities encountered were similar to those observed in non-transplanted patients undergoing therapy with PEG-L-A and included allergic reactions, pancreatitis, weight loss, hypoalbuminemia, and low levels of anti-thrombin III. Of the 24 who received the drug, eight remain in remission. Of 12 patients in second remission at the time of transplantation who received PEG-L-A, five of seven who received allogeneic and two of five who received autologous transplants remain in remission, 16+ to 46+ months from transplant. While PEG-L-A could be administered to most of the patients undergoing marrow transplantation for ALL, most patients either relapsed while receiving the drug or developed toxicities which resulted in abbreviated courses. At this time, we cannot recommend PEG-L-A as single agent, post-BMT chemotherapy.

Adolescent↗

Comparison of fluorescence in situ hybridization, cytogenetic analysis, and DNA index analysis to detect chromosomes 4 and 10 aneuploidy in pediatric acute lymphoblastic leukemia: a Pediatric Oncology Group study.

PURPOSE: Chromosome abnormalities are an important prognostic factor in childhood acute lymphoblastic leukemia (ALL). Recently, a subset of patients with hyperdiploid ALL and trisomy of chromosomes 4 and 10 has been reported to have a very favorable event-free survival. Rapid and accurate detection of these patients will allow them to be treated with highly effective and relatively nontoxic antimetabolite therapy. Because of inherent problems associated with conventional cancer cytogenetics, we examined the efficacy of fluorescence in situ hybridization (FISH) to identify this ALL subgroup. PATIENTS AND METHODS: Fifty uncultured bone marrow specimens from children with newly diagnosed ALL were examined for chromosomes 4 and 10 aneuploidy with FISH. These results were compared with routine cytogenetics and DNA Index (DI). RESULTS: Interphase FISH cytogenetics identified the abnormal cell line(s) in all cases in which cytogenetics showed aneuploidy of chromosomes 4 and 10. In cases in which cytogenetics was not informative, FISH identified the presence of an aneuploid chromosome 4 and/or 10 cell line in concordance with the DI. CONCLUSIONS: FISH interphase cytogenetics can accurately detect chromosome 4 and 10 aneuploidy in leukemic cells. It is a rapid and clinically applicable technique that can reliably identify childhood ALL cases who have trisomy of chromosomes 4 and 10 and who have very favorable event-free survival.

Aneuploidy↗

Maternal selenium levels and sudden infant death syndrome (SIDS).

BACKGROUND: The possibility is tested that low anti-oxidant status and/or low levels of selenium (Se) might predispose to Sudden Infant Death Syndrome (SIDS). AIM: This study was undertaken to collect evidence on the Se status of pregnant and non-pregnant women and newborn babies and to establish whether babies who later died of cot death had significantly divergent levels of blood Se at birth. METHODOLOGY: Aliquots of blood were collected from all newly pregnant mothers in Tasmania and from the cords of all newborn babies. These were analysed for Se and glutathione peroxidase (GPx) content and compared by season and with non-pregnant, age standardised blood donors in three areas of Tasmania and three mainland Australian States. RESULTS: Cot death babies' cordbloods were not significantly different in Se or GPx-status, in this small sample, from those of other babies, nor was a seasonal variation in these parameters demonstrated among 390 randomly selected Tasmanian mothers. Mothers-to-be showed a decrease in enzyme levels during pregnancy and Tasmanian blood donors had significantly lower levels than donors from other States. CONCLUSION: While no evidence can safely be drawn about a relationship between Se or GPx-status and SIDS, this study provides base level measures for populations showing that Tasmanian residents have low levels of these anti-oxidants.

Adult↗

Characterization of 8-(N-methylisopropyl)amino-N6-(5'-endohydroxy- endonorbornyl)-9-methyladenine (WRC-0571), a highly potent and selective, non-xanthine antagonist of A1 adenosine receptors.

Previous studies in our laboratory identified N6-endonorbornyl-9-methyladenine (N-0861) as a highly selective (100-fold) A1-adenosine receptor antagonist (KB = 500 nM). However, its moderate potency limits the degree of A1-receptor blockade that can be achieved by systemically administered N-0861. Structure activity studies were undertaken to invent a compound that had greater affinity for the A1-adenosine receptors than N-0861. C8-N-methylisopropylamino-N6-5'-endohydroxy-N-0861 (WRC-0571) inhibited [3H]-N6-cyclohexyladenosine (CHA) binding to guinea pig A1-receptors with a Ki value of 1.1 nM. WRC-0571 was 200-fold less potent at inhibiting [3H]-5'-N-ethylcarboxamidoadenosine binding to bovine A2a receptors (Ki = 234 nM). WRC-0571 also inhibited the binding of radioligands to cloned human A1, A2a and A3 adenosine receptors with affinities of 1.7, 105 and 7940 nM, respectively. Thus in human adenosine receptors, WRC-0571 is 62-fold selective for the A1 vs. A2a and 4670-fold selective for the A1 vs. A3 receptors; WRC-0571 is therefore the most A1 vs. A3 selective compound yet described. In guinea pig isolated atria, WRC-0571 antagonized the A1-mediated negative inotropic responses to 5'-N-ethylcarboxamidoadenosine (NECA) with a KB of 3.4 nM. WRC-0571 was more than 2500-fold less potent at antagonizing NECA-induced A2b-mediated relaxation in guinea pig aorta. In anesthetized rats WRC-0571 antagonized adenosine-induced bradycardia at concentrations as low as 1 nmol/kg but failed to antagonize A2-mediated hindquarter vasodilation at concentrations up to 10,000 nmol/kg. WRC-0571 is orally active at concentrations as low as 0.3 mumol/kg. WRC-0571 is therefore a highly potent, highly selective antagonist of A1-adenosine receptors both in vitro and in vivo.

Adenine↗

High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells.

Consecutive patients with non-Hodgkin's lymphoma (NHL, n = 133) or Hodgkin's disease (HD, n = 20) were treated with 12.0 Gy of fractionated total body irradiation, etoposide 60 mg/kg, and CY 100 mg/kg followed by infusion of autologous hematopoietic stem cells. Seventy-nine patients received purged (n = 62) or unpurged BM (n = 17), and 74 received unpurged PBSCs alone (n = 56) or with BM (n = 18). The median day for achieving a sustained granulocyte count of 0.5 x 10(9)/I was 14 range (7-66) for BM recipients and 10 (7-30) for PBSC +/- BM recipients (P = 0.03). A platelet count of 20 x 10(9)/I was achieved at a median of day 24 (6-145) in BM recipients and day 11 (range, 7-56) in PBSC +/- BM recipients (P = 0.007). The median number of platelet units transfused was 86 (0-1432) for BM recipients and 30 (6-786) for PBSC +/- BM recipients (P = 0.001). The median number of hospital days was 36 (10-88) for BM recipients and 27 (14-76) for PBSC +/- BM recipients (P = 0.0001). The unadjusted Kaplan-Meier (KM) estimates of survival, event-free survival (EFS) and relapse at 2 years were 0.57, 0.45 and 0.43 for patients receiving BM and 0.55, 0.36 and 0.59 for patients receiving PBSC +/- BM. After adjusting for confounding variables, the estimated relative risk (RR) of death from any cause was 0.92 (P = 0.75), of relapse was 1.25 (P = 0.39), of non-relapse mortality was 0.71 (P = 0.42) and of mortality and/or relapse was 1.17 (P = 0.48) for patients receiving PBSC +/- BM as compared to BM. For 46 patients with NHL receiving unpurged PBSC alone, the unadjusted KM estimate of relapse was 0.61 compared with 0.48 for 52 comparable patients receiving purged BM, while the RR for relapse for patients receiving unpurged PBSCs was 1.37 (P = 0.33) after adjusting for other significant covariates. These data confirm previous observations that patients who receive PBSC +/- BM have faster engraftment, fewer transfusions and shorter hospital stays than patients who receive only BM. There were no statistically significant differences between the two groups in survival, relapse, death from causes other than relapse and event-free survival.

Adolescent↗

Relationship of DNA ploidy to histology and prognosis in rhabdomyosarcoma. Comparison of flow cytometry and image analysis.

BACKGROUND: Although DNA ploidy correlates with prognosis in certain childhood cancers, e.g., neuroblastoma, its significance in rhabdomyosarcoma (RMS) is unclear and controversial. METHODS: Ploidy by flow cytometry (FCM) and image analysis (IA) in 26 of 27 children with RMS (17 embryonal, 3 mixed embryonal/alveolar, 5 alveolar, 1 anaplastic, 1 ectomesenchymoma) and 4 adults with pleomorphic RMS were evaluated. Statistical comparisons were analyzed between DNA content and gender, age, localization, Intergroup Rhabdomyosarcoma Study (IRS) group, and histopathologic subtype. Survival analyses were performed by the Kaplan-Meier test using the approximate chi-square statistic for the log rank test. RESULTS: The concordance rate between FCM and IA was 26 of 30 (87%); FCM was not performed in one tumor. Image analysis was more sensitive than FCM in detecting aneuploidy. Furthermore, DNA content was associated significantly with histologic subtype (P = 0.031); embryonal histology commonly was hyperdiploid (mean, 1.44; median, 1.27), whereas alveolar histology usually was near-tetraploid (mean, 1.83; median, 1.95). All four adult patients with pleomorphic RMS were aneuploid, with one showing multiple DNA peaks. No correlation between DNA content and survival was observed in the children with RMS. However, IRS group (P = 0.011) and patient age (P = 0.036) were independent prognostic indicators significantly related to survival. All adult patients died of their disease. CONCLUSIONS: Although ploidy correlates with histologic subtype, DNA content is not significantly predictive of prognosis in patients with RMS. Age at diagnosis and IRS group are independent predictors of clinical outcome in children with RMS.

Adolescent↗

The endothelium of the rat renal artery plays an obligatory role in A2 adenosine receptor-mediated relaxation induced by 5'-N-ethylcarboxamidoadenosine and N6-cyclopentyladenosine.

Studies were undertaken in the rat isolated renal artery in order to determine if adenosine receptor agonists were capable of inducing the release of nitric oxide from the renovascular endothelium. N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA) produced concentration-dependent relaxations in endothelium intact renal artery rings. The NECA curve was biphasic with a first phase pA50 of 6.05. The CPA curve was monophasic with a pA50 of 4.35. In the absence of endothelium the curves to both NECA and CPA were monophasic with pA50 values of 3.37 and 3.50, respectively. The A2a adenosine receptor-selective agonist CGS21680 (2-[p-(2-carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamidoadenos ine) was inactive in endothelium intact tissues. Relaxant responses to CPA and NECA in the presence of endothelium were antagonized by 8-p-sulfophenyltheophylline and by 1,3-dipropyl-8-cyclopentylxanthine only at a nonselective concentration (3 x 10(-6) M) suggesting activation of A2 adenosine receptors. The responses to CPA and NECA in the absence of endothelium are not due to activation of A1 or A2 adenosine receptor subtypes because they are resistant to blockade by these xanthines. CPA and NECA responses in the presence of endothelium were inhibited by NG-nitro-L-arginine methylester (L-NAME), a nitric oxide synthase inhibitor, but not by the cyclooxygenase inhibitor indomethacin or the K+ATP channel antagonist glibenclamide. These results suggest that the rat renal artery contains A2b adenosine receptors that are located exclusively on the endothelium and cause the release of nitric oxide.

Adenosine↗

Identification and functional characterization of A1 and A2 adenosine receptors in the rat vas deferens: a comparison with A1 receptors in guinea pig left atrium and A2 receptors in guinea pig aorta.

This study was undertaken to characterize the adenosine receptors in the rat vas deferens. Because adenosine receptors have been well characterized in the cardiovascular system of the guinea pig, antagonist dissociation constants (pKB values) in the rat vas deferens were compared with those from the left atrium (A1) and the aorta (A2) of the guinea pig. The A1-selective agonists (+/-)-N6-endonorbornan-2-yl-5'-N-hydroxy ethylcarboxamidoadenosine (N-0723) and N6-cyclohexyladenosine (CHA) and the nonselective agonist 5'-N-ethylcarboxamidoadenosine (NECA) inhibited the electrically evoked contractions of both the vas deferens and left atrium with a potency order of N-0723 > NECA = CHA. The A2a-selective agonist 2-[p-(2-carboxyethyl)-phenethylamino]5'-N-ethylcarboxamidoadenosin e (CGS21680) was equipotent to NECA in the vas deferens but was 500-fold less potent than NECA in the left atrium. In the aorta only NECA was a potent agonist. The nonselective adenosine receptor antagonist 8-phenyltheophylline antagonized the responses in all three tissues with approximately equal potency (pKB approximately 6.6). In the rat vas deferens, the A1-selective antagonists (+/-)-N6-endonorboman-2-yl-9-methyladenine (N-0861) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) were more potent at antagonizing the responses to A1-selective agonists (pKB approximately 8.8 and 6.4, respectively) than they were at antagonizing the responses to NECA and CGS21680 (pKB = 6.3 and < 5, respectively). However, in the left atrium, N-0861 (pKB = 6.2) and DPCPX (pKB = 8.9) were no more potent in antagonizing responses to the A1-selective agonists than they were in antagonizing responses to NECA.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine↗

Trade and migration: the case of NAFTA.

"This article provides background information on NAFTA [the North American Free Trade Agreement], reviews data on its economic effects, and summarizes studies and projections of NAFTA's likely effects on Mexico-to-U.S. migration. Migration factors (demand-pull, supply-push, and networks) are examined to determine whether NAFTA's effect on economic development particularly in the border areas will accelerate or retard migration. The conclusion is that NAFTA is likely to produce a temporary migration hump, slightly raising already high migration levels in the 1990s, but reducing the volume of Mexico-to-U.S. migration that would otherwise occur over subsequent decades."

Americas↗