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M Wagstaff

Publications and source records attributed to M Wagstaff.

At least 19 recordsLinked to original sources
PubMed2001

Cerebro-splanchnic oxygenation ratio (CSOR) using near infrared spectroscopy may be able to predict splanchnic ischaemia in neonates.

OBJECTIVE: To investigate whether near infrared spectroscopy (NIRS) can detect differences in oxyhaemoglobin signal when applied to the abdomens of neonates with surgically proven splanchnic ischaemia. DESIGN: Prospective, observational cohort study. SETTING: Tertiary neonatal referral centre. PATIENTS: Medical and surgical neonates were studied. Two groups were identified, neonates with acute abdomens referred for surgery and those with normal abdomens admitted for medical reasons. INTERVENTIONS: Tissue oxygenation indexes (TOI) of cerebral and splanchnic regions were measured using near infrared spectroscopy (NIRS) and their relative values expressed as a cerebro-splanchnic oxygenation ratio (CSOR). Measurements were made on admission or immediately prior to surgery and subsequently repeated on a daily basis, whenever possible, until discharge from our unit. The area under the receiver operating characteristic (ROC) curve was evaluated and optimum diagnostic cut-off values determined. RESULTS: Forty neonates were studied: 10 with acute abdomens, including four with necrotising enterocolitis (NEC), 29 controls with normal abdomens and one with cerebral hypoxic ischaemic injury. Median CSOR for the control group was 0.96 (interquartile range 0.83-1.02) whereas the acute abdomen group had a significantly lower median CSOR value of 0.66 (0.45-0.69) (p<0.001). The area under the ROC was 0.91 (95% confidence limits 0.78-1.00) for CSOR. Taking a boundary value of CSOR for the prediction of splanchnic ischaemia as less than 0.75, intestinal ischaemia was identified with a positive predictive value of 0.75 (0.43-0.95) and excluded with a negative predictive value of 0.96 (0.81-1.0). This was a better performance than using abdominal TOI alone. CONCLUSIONS: By comparing the TOI of cerebral and splanchnic regions it may be possible to establish the presence of normal splanchnic perfusion and detect when splanchnic ischaemia develops. CSOR had a 90% (56-100%) sensitivity to detect splanchnic ischaemia in neonates. Further work is necessary to confirm these early findings and establish whether abdominal NIRS has a clinical role in detecting splanchnic ischaemia.

Abdomen, Acute↗
PubMed1995

Acute promyelocytic leukaemia (M3): relapse with acute myeloblastic leukaemia (M2) and dic(5;17) (q11;p11).

Secondary leukaemia following treatment of M3 acute promyelocytic leukaemia (APL) is a rare event. We describe a patient in remission following chemotherapy for APL who relapsed with M2 acute non-lymphoblastic leukaemia (ANLL). The original t(15;17) (q22;q21) chromosome translocation was lost and replaced by a clone containing a dic(5;17) (q11;p11) abnormality. Southern genomic analysis demonstrated re-arrangements of the retinoic acid receptor varies; is directly proportional to (RAR varies; is directly proportional to) and PML genes in the APL blasts at presentation but not in the M2 ANLL marrow at relapse. The significance of unbalanced 5;17 translocations as markers for therapy-related secondary leukaemia is discussed.

Blotting, Southern↗
PubMed1995

Th1 cells specific for HIV-1 gag p24 are less efficient than Th0 cells in supporting HIV replication, and inhibit virus replication in Th0 cells.

This report provides three lines of evidence to suggest that T-helper type 1 (Th1) and type 0 (Th0) cells could play an opposing role in acquired immune deficiency syndrome (AIDS). Using a panel of Th1 and Th0 clones specific for human immunodeficiency virus-1 (HIV-1) gag p24, derived from seronegative volunteers immunized with gag p24: Ty virus-like particles, a Th1 clone specific for tuberculin (PPD), and a Th0 clone derived by random activation from the same volunteer, we have demonstrated the following differences in the capacity of these clones to regulate the in vitro replication of HIV. (1) Th1 clones were less efficient than Th0 clones in supporting HIV replication, both in their resting state (by 10-1000-fold) and after antigen activation (by five to 100-fold). Furthermore, the infectious titre of HIV recovered from the Th0 population was more than 1000-fold higher than virus from the Th1 population, and the number of HIV-infected Th0 cells was five to 16 times higher than the number of infected Th1 cells. (2) Antigen- or mitogen-activated Th1, but not Th0 clones, inhibited HIV in bystander CEM-4 cells. Th1 cells also inhibited HIV in autologous and allogeneic Th0 cells. The level of inhibition in these experiments ranged from 50% to 100% and was three to 10-fold higher and more sustained in the presence of p24-specific clones compared to the PPD-specific Th1 clone. The capacity of Th1 cells to inhibit HIV in neighbouring cells was also reflected in the reduced replication of HIV in the clones immediately after antigen activation compared to unstimulated cells. Kinetic studies of virus production, cytokine release and proliferation showed that inhibition of HIV was associated with peak cytokine release and preceeded proliferation. (3) The Th1 clones had higher cytolytic potential than the Th0 clones. Therefore, the HIV inhibitory activity of Th1 cells could be partly due to cell to cell killing. These data demonstrate the opposing effects of Th1 and Th0 cells on the in vitro replication of HIV, and suggest that Th1 cells might be important in immunity whereas Th0/Th2 cells might lay a role in promoting disease.

CD4-Positive T-Lymphocytes↗
PubMed1991

Detection of two-component mixtures of lognormal distributions in grouped, doubly truncated data: analysis of red blood cell volume distributions.

We have examined the statistical requirements for the detection of mixtures of two lognormal distributions in doubly truncated data when the sample size is large. The expectation-maximization algorithm was used for parameter estimation. A bootstrap approach was used to test for a mixture of distributions using the likelihood ratio statistic. Analysis of computer simulated mixtures showed that as the ratio of the difference between the means to the minimum standard deviation increases, the power for detection also increases and the accuracy of parameter estimates improves. These procedures were used to examine the distribution of red blood cell volume in blood samples. Each distribution was doubly truncated to eliminate artifactual frequency counts and tested for best fit to a single lognormal distribution or a mixture of two lognormal distributions. A single population was found in samples obtained from 60 healthy individuals. Two subpopulations of cells were detected in 25 of 27 mixtures of blood prepared in vitro. Analyses of mixtures of blood from 40 patients treated for iron-deficiency anemia showed that subpopulations could be detected in all by 6 weeks after onset of treatment. To determine if two-component mixtures could be detected, distributions were examined from untransfused patients with refractory anemia. In two patients with inherited sideroblastic anemia a mixture of microcytic and normocytic cells was found, while in the third patient a single population of microcytic cells was identified. In two family members previously identified as carriers of inherited sideroblastic anemia, mixtures of microcytic and normocytic subpopulations were found. Twenty-five patients with acquired myelodysplastic anemia were examined. A good fit to a mixture of subpopulations containing abnormal microcytic or macrocytic cells was found in two. We have demonstrated that with large sample sizes, mixtures of distributions can be detected even when distributions appear to be unimodal. These statistical techniques provide a means to characterize and quantify alterations in erythrocyte subpopulations in anemia but could also be applied to any set of grouped, doubly truncated data to test for the presence of a mixture of two lognormal distributions.

Adolescent↗
PubMed1990

Chronic neutrophilic leukemia and multiple myeloma. An association with lambda light chain expression.

Two patients with plasma cell dyscrasia and IgG lambda paraproteinemia in association with the rare disorder, chronic neutrophilic leukemia (CNL), are described. Cytogenetic studies excluded Philadelphia + chronic myeloid leukemia and molecular analysis of the breakpoint cluster region (bcr) revealed no evidence of clonal gene rearrangement. Nine similar cases of coexistent CNL and paraproteinemia have been identified in the literature and attention is drawn to the disproportionate excess of lambda light chain restriction in this subset of patients. Evidence supporting a clonal origin of CNL is considered and the nature of the relationship between the chronic myeloid expansion and the development of multiple myeloma is discussed.

Aged↗
PubMed1990

Molecular biology and leukaemia diagnosis.

The diagnosis and classification of leukaemia started with simple morphological examination and now embraces use of special stains, cytochemistry and immunophenotyping. Genetic studies have progressed from karyotyping to detection of genetic changes within genes. The methods described in this chapter are still at an early stage of development and, so far, have provided relatively little in the way of an extension of available diagnostic information. Sometimes the methods provide extensions to existing techniques, for example by the detection of bcr rearrangements in patients who have CML or ALL but do not have a detectable Philadelphia chromosome. Another example is retrospective diagnosis of gene rearrangements using DNA from slide preparations. However, it should be noted that it has only very recently been shown that there is likely to be a causal relationship between the Ph chromosome and leukaemia. Daley et al (1990) induced CML in mice by bone marrow transplantation of cells infected with a retrovirus encoding P210bcr/abl and Heisterkamp et al (1990) produced mice transgenic for a BCR/ABL P190 DNA construct and showed that the progeny died of acute leukaemia (mostly ALL). We have not summarized studies of the incidence of activated oncogenes such as RAS in leukaemia and myelodysplasia. Such oncogenes appear to be involved in many tumours and may well indicate either a predisposition to cancer or a particular stage of malignancy, but their analysis does not at present help in making a diagnosis. It is likely that, as we understand more about the nature of the malignant process, we shall be able to use genetic techniques to enhance considerably both diagnostic and prognostic precision.

DNA↗
PubMed1986

Ferritin expression in transformed human haemopoietic cell lines.

Isoferritins found in a number of human haemopoietic cell lines do not correspond to the isoferritins found widely distributed in normal tissues. It is suggested that these proteins may result from the expression of otherwise silent genes known to be present in the human genome.

Amino Acid Sequence↗
PubMed1984

Biochemical and immunological characteristics of ferritin from HL-60, U-937 and K-562 cell lines: implications for haemopoietic regulation.

It has been suggested that acidic isoferritins play a major role in the regulation of human granulocyte-macrophage (CFU-GM) proliferation. Such regulatory isoferritins are said to occur in some human tissues including both leukaemic and normal leucocytes, and certain established cell lines. They are glycosylated and bind to Con A. Extracts from HL-60, U-937 and K-562 cell lines are said to contain inhibitory activity but only in HL60 cells is the activity neutralized by antibody to acidic isoferritins. The properties of ferritin from these cell lines have been investigated. HL60 and U-937 extracts contained predominantly basic (spleen-type) isoferritins and K-562 extracts predominantly acidic (heart-type) isoferritins on immunoradiometric assay. None of the ferritin bound to Con A. On anion exchange chromatography ferritin from U-937 was basic in character, that from K-562 was acidic and HL-60 contained a variety of isoferritins. The identification of glycosylated acidic isoferritins as inhibitors of granulopoiesis appears to be an oversimplification and the classification of isoferritins on the basis of two subunit types may also need revision.

Cell Line↗
PubMed1984

The fitness opportunity for dietetic educators and practitioners.

This article describes an academic experience in developing the nutrition component of a community fitness program. It illustrates how the role modeling of faculty and students can lead to the creation of new positions in nontraditional settings. Information is based on the involvement of the Coordinated Undergraduate Program (CUP) at Viterbo College, LaCrosse, WI, in the LaCrosse Exercise Program at the University of Wisconsin-LaCrosse. Included are (a) a rationale for involvement in exercise programs; (b) a perspective on attitudes, knowledge, and skills required for practice in a fitness environment; and (c) suggestions on possible curriculum components applicable to a fitness program that incorporates a nutrition emphasis.

Attitude to Health↗
PubMed1982

Iron and isoferritins in iron overload.

1. The ferritin content of iron-overloaded tissues was higher than that of normal tissues. There was also an increased iron content of ferritin extracted from these tissues. 2. In the limited number of tissues that we examined haemosiderin deposition appeared to be greater in the iron-overloaded livers than in the iron-overloaded spleens. 3. Ferritins extracted from iron-overloaded liver, spleen and kidney had similar properties to those extracted from the corresponding normal tissues. 4. Ferritin from iron-overloaded heart had a greater proportion of more basic isoferritins than had ferritin from normal heart. 5. Immunoreactivity to heart and spleen ferritin antibodies, subunit composition, iron content and rate of iron uptake of both unfractionated ferritin and isoferritin fractions separated by ion exchange chromatography were related to the isoelectric point.

Chromatography, Ion Exchange↗
PubMed1982

The clearance of 131I-human plasma ferritin in man.

Ferritin was purified 33,000-fold from the plasma of patients with idiopathic hemochromatosis. The plasma ferritin was labeled with 131I and injected into 2 normal men. Clearance was found to be relatively slow, with 50% 131I-ferritin remaining in the plasma at 27-30 hr. The fraction of plasma ferritin that bound to concanavalin-A was found to be cleared more slowly than the nonbinding fraction. These findings confirm our previous suggestion that glycosylation is a major factor prolonging the survival of ferritin in the plasma, but differ from the results of earlier studies in experimental animals and preterm infants, which indicated very rapid plasma ferritin turnover.

Animals↗
PubMed1981

Detection of a glycosylated subunit in human serum ferritin.

Ferritin was purified from the serum of two patients with idiopathic haemochromatosis. The protein contained three types of subunit--the H and L subunits of tissue ferritins (although only a trace of H could be detected) and a third subunit, 'G', with the highest apparent molecular weight. Only the 'G' subunit band stained for carbohydrate, indicating that a proportion of the subunits of human serum ferritin are glycosylated. Although serum was obtained from patients with idiopathic haemochromatosis, it is probable that the 'G' subunit is a component of normal serum ferritin.

Concanavalin A↗
PubMed1980

Sialic acid and the microheterogeneity of human serum ferritin.

1. Ferritin has been partially purified from the serum of patients with idiopathic haemochromatosis. 2. Incubation with neuraminidase of this partially purified serum ferritin eliminated much of the microheterogeneity of the protein so that only ferritin of isoelectric point approximately 5.8 was present. 3. There was no change in the total amount of ferritin present (measured immunologically) or in the percentage of ferritin binding to concanavalin A. 4. Incubation of liver, spleen or heart ferritin with neuraminidase did not change the isoelectric focusing patterns.

Concanavalin A↗