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M Blake

Publications and source records attributed to M Blake.

At least 55 records · Page 3Linked to original sources
PubMed1994

Comparative study of the survival rate of frozen-thawed embryos with perforated zonae from microsurgical fertilization and frozen-thawed embryos with intact zonae.

OBJECTIVE: To compare the survival rate of frozen-thawed embryos with perforated zonae from microsurgical fertilization (subzonal insemination) (SUZI) with that of embryos with intact zonae. DESIGN: Thirty-eight embryos resulting from microsurgical fertilization by SUZI were cryopreserved in 16 patient cycles. Within the same period, 140 zonae-intact embryos from 46 patient cycles were cryopreserved. The survival rate of the SUZI embryos was compared with the zonae-intact embryos after thawing. Clinical pregnancies were compared after the transfer of the thawed embryos. RESULTS: The total survival rates were 94.7% and 89.3% for thawed SUZI embryos and zonae-intact embryos, respectively. Within each type of embryo, total survival rates were similar irrespective of the age of the embryos at freezing. The blastomere loss per thawed embryo was the same for zonae-intact and SUZI embryos. One clinical pregnancy was obtained in patients who received thawed SUZI embryos and nine in patients who received embryos with intact zonae. CONCLUSIONS: It is concluded that SUZI embryos can be cryopreserved and thawed with the same degree of confidence as zonae-intact embryos. The low implantation rate of thawed SUZI embryos requires confirmation in a larger clinical series.

Cryopreservation↗
PubMed1994

Constructing regions for small area analysis: material deprivation and colorectal cancer.

BACKGROUND: This paper is about constructing small areas for the analysis of health data with the aims of health service delivery in mind. The areal framework should enable the analyst to link health data and census data and the areas should have large enough populations to ensure that rates are reliable and be homogeneous with respect to important socio-economic attributes. METHODS: An information-based statistic is used for the construction of regions in Sheffield based on the Townsend deprivation index. Enumeration districts are used as the geographical building blocks for the regions. The new regional framework is used for computing Bayes adjusted standardized incidence rates for colorectal cancer (CRC) across Sheffield. The paper then examines the statistical relationship between CRC incidence and deprivation across the set of regions using bivariate regression. RESULTS: The method yields regions that are considerably more homogeneous in terms of deprivation than wards, and using this framework it is shown that there is a (weak) statistical association at the regional scale between deprivation and CRC. CONCLUSION: We conclude that statistical tools can be employed to provide regions that meet the criteria for small area analysis of health data and the analyst does not have to be tied to large administrative units such as wards. There are some benefits to executing this work within a Geographic Informative System. The method should be of interest to those concerned with health service delivery and the identification of 'problem regions'.

Bayes Theorem↗
PubMed1994

Immunogenicity and evolutionary variability of epitopes within IgA1 protease from serogroup A Neisseria meningitidis.

Five murine epitopes were defined and mapped within IgA1 protease produced by Neisseria meningitidis. Epitopes 1 and 2 were present in IgA1 protease from all strains, and from Neisseria gonorrhoeae. Epitopes 3 through to 5 varied between subgroups of serogroup A meningococci, but have remained constant over decades within the subgroups, except for epitope 4, which changed between 1983 and 1987 during the spread of subgroup III meningococci from Asia to Africa. Binding of monoclonal antibodies to epitopes 1, 4 and 5 neutralized enzymatic function. Human sera containing antibodies to IgA1 protease as a result of natural infection inhibited binding of monoclonal antibodies to epitope 4 but not to the other epitopes.

Animals↗
PubMed1994

c-myc Down-regulation in suramin-treated HL60 cells precedes growth inhibition but does not trigger differentiation.

Down-regulation of c-myc mRNA expression is linked to growth arrest and the state of differentiation of hematopoietic cells. We showed that treatment of HL60 cells with suramin results in a rapid reduction of c-myc expression followed by an inhibition of cell growth. Both c-myc mRNA and protein levels decreased by day 1 of treatment, and, by day 4, only 10% of control c-myc protein levels were detected. In contrast to retinoic acid, dimethyl sulfoxide, and 12-O-tetradecanoylphorbol-13-acetate treatment, however, exposure of HL60 cells to suramin did not result in the induction of differentiation. These results demonstrate that suramin modulates c-myc levels in HL60 cells and that the down-regulation of c-myc is not sufficient to trigger differentiation toward either granulocytic or monocytic lineages.

Cell Differentiation↗
PubMed1993

A clinical evaluation of a blood conservation device in medical intensive care unit patients.

OBJECTIVES: This study was designed to a) document the efficacy of a device intended to conserve blood in critically ill patients; b) determine the effect of this blood conservation on hemoglobin concentration and the need for blood transfusions; c) determine if the blood conservation device resulted in interference with arterial pressure waveforms; d) determine if use of the blood conservation device resulted in a difference in the number of accidental needle punctures suffered by healthcare workers. DESIGN: Prospective, randomized, controlled trial. A clinical trial using prospective, random allocation of consecutive eligible patients. SETTING: The medical intensive care unit (ICU) of a university hospital located in a large metropolitan area. PATIENTS: A total of 100 patients who were admitted to the medical ICU, required arterial line monitoring for clinical purposes, and were managed by the ICU medical service. Exclusion criteria included active bleeding or chronic renal failure at the time of ICU admission. INTERVENTIONS: Patients in the experimental group had a blood conservation device incorporated into the arterial pressure monitoring system, while patients in the control group received a conventional arterial pressure monitoring system. MEASUREMENTS AND MAIN RESULTS: Data gathered included: age; gender; ICU discharge status; the duration of ICU stay; time in the study; volume of all blood drawn, discarded, or lost due to leakage; hemoglobin concentrations; blood transfusions; and accidental needle injuries. Arterial pressure waveforms were recorded and inspected for dampening or other deformation. Mean hemoglobin concentrations were compared on ICU admission and at 12-hr intervals. Demographic and clinical characteristics of the two groups were not significantly different. The volume of blood drawn and discarded from arterial catheters was significantly lower in the blood conservation group (blood conservation device: 5.7 +/- 7.5 mL; control: 96.4 +/- 88.5 mL; p < .0001), as was the total volume of blood discarded (blood conservation device: 19.4 +/- 47.4 mL; control: 103.5 +/- 99.9 mL; p < .0001). Mean hemoglobin concentration on admission was similar in the two groups (blood conservation device group: 11.8 +/- 2.5 g/dL; control group: 12.6 +/- 2.3 g/dL). In both groups, the mean hemoglobin concentration declined most rapidly in the first 24 hrs of ICU care and, thereafter, declined more slowly. Although the mean hemoglobin concentration was higher in the blood conservation group after 6 days, statistical significance was not reached until 9.5 days of ICU care. The mean change in hemoglobin concentration (overall: 1.2 +/- 2.2 g/dL) during the study represents a statistically significant (p < .0001) decrease of 9.7%. Hemoglobin concentration during the study decreased by 1.4 +/- 2.2 g/dL in the control group and 1.0 +/- 2.3 g/dL in the blood conservation group (p = nonsignificant). Univariate and multiple regression analysis demonstrated discarded blood volume to be a significant and independent predictor of the decline in hemoglobin concentration. Transfusion requirements were similar in both groups. The blood conservation system did not alter or interfere with pressure waveforms. There were no accidental needle injuries noted. CONCLUSIONS: The conservation of blood in critically ill patients must be a high-priority concern of all healthcare workers. Our data indicate that the blood conservation system eliminates a significant factor in the decline in hemoglobin concentration. With devices as described here, there is no reason to continue the practice of wasting the blood of critically ill patients in order to prevent preanalytic error.

Adult↗
PubMed1993

Autoantibodies to the protein core of vascular basement membrane heparan sulfate proteoglycan in systemic lupus erythematosus.

Vascular heparan sulfate proteoglycan (vHSPG) has an important role in the normal vasculature, including hemostasis, lipolysis and other vascular functions. These functions are mediated by both the glycosaminoglycan and protein core moieties of vHSPG. Autoimmunity to vHSPG has been demonstrated to play a role in vascular injury in animal models, and is present in patients with autoimmune vascular disease. However, most previous studies of human autoimmunity to vHSPG have only investigated heparan sulfate glycosaminoglycan epitopes. In the current investigations, autoantibodies to the protein core of vHSPG in sera from patients with systemic lupus erythematosus (SLE) were investigated. vHSPG protein core was prepared by chemical deglycosylation. Competitive immunoinhibition ELISA and immunoblotting immunoassays were established employing monoclonal antibodies to vHSPG protein core. SLE sera were demonstrated to contain IgG autoantibodies reactive with the vHSPG protein core by immunoblotting. Human autoantibodies to vHSPG protein core were not inhibited by heparan sulfate confirming their protein core reactivity. Competitive immunoinhibition studies employing a solid phase radioimmunoassay also confirmed the reactivity of human sera with vHPSG protein core. By ELISA, a significant increase in the occurrence of anti-vHSPG protein core antibodies was noted in SLE sera. While most previous investigations have demonstrated autoimmunity to heparan sulfate, the presence of IgG autoantibodies to vHSPG protein core demonstrates that the entire vHSPG proteoglycan is the target of autoimmunity in SLE.

Animals↗
PubMed1993

Digital clubbing. A case study.

In this case, it is difficult to assess whether the severity of the clubbed digits is a result of a purely hereditary nature, liver pathology, chronic respiratory ailments, or a combination of the above. The abnormal liver function test may not be related to the digital clubbing. Instead, they may be the result of the alcohol abuse. The case does appear to be hereditary because his siblings and mother all have clubbed digits and there is a higher frequency in blacks. The authors believe that this case affords an opportunity to make the podiatrist aware of the possibilities that should be considered the differential diagnosis when examining a patient with clubbed digits. It is important to fully work up a patient with clubbed digits even if the presentation is that of hereditary clubbing. Severe clubbing may be the result of a mild hereditary form that was worsened by an underlying systemic condition, such as malignancy, toxicosis, endocrinopathy, and neuropathy.

Adult↗
PubMed1992

Inhibition of acute myelogenous leukemia blast proliferation by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors.

Interleukin-1 (IL-1) has recently been reported to play an important role in acute myelogenous leukemia (AML) blast proliferation. We therefore investigated the effect of soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) on the growth of AML bone marrow blast progenitors from 25 patients. In the AML blast colony culture assay, sIL-1R and IL-1RA inhibited blast colony-forming cell replication in a dose-dependent fashion, at concentrations ranging from 10 to 500 ng/mL (sIL-1R) and 10 to 1,000 ng/mL (IL-1RA), and their inhibitory effect was partially reversed by IL-1 beta. A similar inhibitory effect was also noted with the use of anti-IL-1 beta neutralizing antibodies. When AML blast progenitors were grown either in the presence of fetal calf serum (FCS) alone or with one of the following: phytohemagglutinin leukocyte-conditioned medium (PHA-LCM), granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, interleukin-3 (IL-3), or stem cell factor (SCF), addition of 100 ng/mL sIL-1R or IL-1RA inhibited blast colony formation by 3% to 96% and 2% to 97%, respectively. In sharp contrast, neither of these IL-1-inhibitory molecules significantly inhibited proliferation of normal marrow hematopoietic progenitors. Lysates of 2 x 10(7) low-density AML marrow cells were tested for intrinsic IL-1 beta content using an enzyme-linked immunoadsorbant assay (ELISA). Samples from five of six patients showed high concentrations (ranging from 501 to 2,041 pg), whereas 2 x 10(7) cells from two normal marrow aspirates yielded 54.6 pg of IL-1 beta. AML blast colony-forming cells from all six patients were inhibited by sIL-1R, IL-1RA, or both. Incubation of nine samples of AML low-density cells with either sIL-1R or IL-1RA reduced GM-CSF concentrations in cell lysates, and supernatants from nine (P less than .01) and six samples (P less than .037), respectively, and G-CSF concentration in lysates from six of nine samples (P less than .03), and in supernatants from five of six samples (P less than .06) when studied by ELISAs. Our data implicate IL-1 in AML blast proliferation and suggest the potential benefits of using IL-1-inhibitory molecules in future therapies for AML.

Adult↗
PubMed1991

Suppression of chronic myelogenous leukemia colony growth by interleukin-1 (IL-1) receptor antagonist and soluble IL-1 receptors: a novel application for inhibitors of IL-1 activity.

In this study, we investigated the role of interleukin-1 beta (IL-1 beta) in the malignant evolution of chronic myelogenous leukemia (CML) and the functional activity of IL-1 inhibitors. Bone marrow (BM) and peripheral blood (PB) low-density cells from 38 CML patients were studied in the colony-forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte colony culture assay. Samples from patients with early stage, interferon-alpha (IFN)-sensitive disease formed hematopoietic colonies in the presence of fetal calf serum (FCS), erythropoietin (Epo), and one of the following: granulocyte-macrophage colony-stimulating factor (10 ng/mL), IL-3 (15 ng/mL), both, or phytohemagglutinin-conditioned medium. The addition of IL-1 beta augmented IFN-sensitive CML colony growth in a dose-dependent manner at concentrations of 10 to 100 U/mL. In sharp contrast, addition of the above growth factors did not augment the colony growth-promoting effect of FCS and Epo in samples from IFN-resistant patients; further, adherent cell fractionation or T-lymphocyte depletion attenuated the "autonomous" colony growth. Lysates of 2.5 x 10(7) low-density cells from each of six IFN-resistant and six IFN-sensitive CML patients and three normal volunteers were tested for intrinsic IL-1 beta content in an enzyme-linked immunosorbent assay and yielded a mean of 610 pg, 54.6 pg, and 49.4 pg of IL-1 beta, respectively (P less than .045). Interestingly, both soluble IL-1 receptors (sIL-1R) and IL-1 receptor antagonist (IL-1RA) at concentrations of 5 to 100 ng/mL (sIL-1R) and 10 to 500 ng/mL (IL-1RA) inhibited CML colony growth in a dose-dependent fashion, with maximal inhibition of 64% and 65%, respectively. A similar effect was noted with the use of anti-IL-1 beta neutralizing antibodies. These data implicate IL-1 beta in CML disease progression and suggest that the inhibitory effects of molecules such as sIL-1R and IL-1RA could conceivably be the basis of a novel therapeutic strategy against this disorder.

Adolescent↗
PubMed1991

Granulocyte-macrophage colony-stimulating factor and interleukin-3 in combination: a potent and consistent myelodysplastic syndrome bone marrow stimulant in vitro.

In an effort to overcome bone marrow failure in myelodysplastic syndrome (MDS), we have investigated recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) in phase I-II clinical trials. Although these agents partially increased peripheral blood granulocyte counts, their effect on other hematopoietic lineages was generally sporadic. Since in vitro analysis and in vivo studies in primates indicate that GM-CSF and IL-3 synergistically enhance hematopoietic stem cell proliferation, we evaluated their combined effect on marrow progenitors obtained from ten MDS patients. When used singly, each growth factor stimulated replication of granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) colony-forming cells in a dose-dependent fashion. When colony-stimulating activity was compared at concentrations that maximally amplified individual MDS patients' colony numbers, IL-3 was a more potent stimulant in some patients and GM-CSF in others. When used in combination, IL-3 plus GM-CSF was more effective than each growth factor by itself in five of six patients. Our data indicate that the MDS hematopoietic progenitor stimulatory effect of these growth factors varies from patient to patient. However, the combination of GM-CSF and IL-3 appears to be more potent than the individual molecules in the majority of patients.

Bone Marrow↗
PubMed1991

Effects of protein I of Neisseria gonorrhoeae on neutrophil activation: generation of diacylglycerol from phosphatidylcholine via a specific phospholipase C is associated with exocytosis.

Upon engagement of chemoattractant receptors, neutrophils generate inositol trisphosphate and diacylglycerol (DG) by means of a phosphatidylinositol-specific phospholipase C (PI-PLC) which is regulated by a GTP-binding protein(s). We have previously reported (Reibman, J., H. M. Korchak, L. B. Vosshall, K. A. Haines, A. M. Rich, and G. Weissmann. 1988. J. Biol. Chem. 263:6322-6328) a biphasic rise in DG after exposure of neutrophils to the chemoattractant FMLP: a rapid (less than or equal to 15 s) phase ("triggering") and a slow (greater than or equal to 30 s) phase ("activation"). These derive from distinct intracellular lipid pools. To study the source of rapid and slow DG, we have used a unique probe, protein I, a porin that is the major outer membrane protein of Neisseria gonorrhoeae. Treatment of neutrophils with protein I inhibits exocytosis and homotypic cell adhesion provoked by FMLP without inhibiting assembly of the NADPH oxidase responsible for O2-. generation. DG turnover in PMN labeled with [3H]arachidonate and [14C]glycerol was profoundly altered by protein I. Whereas the rapid peak of DG was only modestly diminished (FMLP vs. FMLP plus protein I = DG labeled with [3H]arachidonic acid (3H-a.a.-DG): 142 +/- 14% SEM vs. 125 +/- 22%; DG labeled with the glycerol backbone with [14C]glycerol (D-14C-G): 125 +/- 10% SEM vs. 107 +/- 8.5% SEM), the slow rise in both 3H-a.a.-DG and D-14C-G was essentially abolished. Moreover, treatment of neutrophils with 4-4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), which, like protein I, inhibits exocytosis without affecting O2-. generation also inhibited slow DG. However, protein phosphorylation and dephosphorylation (47phox, 66phox) were unaffected in the absence of slow DG. To determine the source of the slow DG, we have analyzed radiolabeled phospholipid (PL) turnover after FMLP +/- protein I (P.I.). Treatment of PMN with FMLP (0.1 microM) resulted in breakdown of phosphatidylcholine (PC), beginning at 30 s, and reaching a nadir at 60 s (3H-PC = 59 +/- 10.2% SEM of resting, 14C-PC = 57 +/- 6.4%). Protein I (0.25 microM) significantly inhibited PC turnover after FMLP ([3H]PC = 95 +/- 5.6% and [14C]PC = 86 +/- 8.4% of resting at 60 s), but failed to alter the metabolism of 3H- or 14C-phosphatidylinositol after FMLP (91 +/- 19.6 and 88 +/- 16.5% vs. 92 +/- 9.2 and 91 +/- 16% at 60 s).(ABSTRACT TRUNCATED AT 400 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Pilin expression and processing in pilus mutants of Neisseria gonorrhoeae: critical role of Gly-1 in assembly.

Spontaneous mutants of Neisseria gonorrheae failing to express pili or having diminished levels of piliation were studied with regard to pilin expression. All mutants displayed altered pilin processing detectable as the release of soluble, truncated pilin molecules (S-pilin). Of particular interest was the finding, in one mutant, that substitution of serine for glycine at position -1 of propilin, a highly conserved residue among N-metPhe and related pilins, abolished pilus expression but not S-pilin release. The degree of S-pilin processing and the levels of membrane-associated pilin varied among the different classes of mutants, suggesting that each was blocked at a distinct step of pilus biogenesis. The data support a model in which increased S-pilin processing is a result of a decreased rate of pilus polymerization.

Amino Acid Sequence↗
PubMed1991

Assessment of nutrient intake in association with weight loss after gastric restrictive procedures for morbid obesity.

Postoperative nutrient intakes were examined in patients who were losing weight in an early period following gastric restrictive surgery for morbid obesity (3 to 6 months post-surgery), and patients whose reduced weight was relatively stable at 1 to 2 years post-surgery. In association with weight loss, patients showed increased physical activity and reduced energy intakes which were frequently less than the Recommended Daily Intakes (RDI), particularly in the early period. Protein intake was also below recommended levels in the two post-operative phases. The intakes of iron, folate and calcium were below the recommended levels in the early postoperative phase. The intakes of iron and folate were also below recommended levels in the late postoperative phase. The study indicates the potential for deficiencies of iron, folate and calcium after gastric restrictive surgery and supports the importance of careful and prolonged follow-up of these patients, with particular attention to nutritional status.

Adult↗
PubMed1991

Role of E2F transcription factor in E1A-mediated trans activation of cellular genes.

Adenovirus E1A-dependent trans activation of the adenovirus E2 gene involves the activation of the cellular transcription factor E2F. E2F binding sites have also been identified in the 5'-flanking region of a number of cellular genes, raising the possibility that such genes are targets for E1A trans activation. We now demonstrate that two genes that possess E2F recognition sites, N-myc and DHFR, are stimulated by E1A, dependent on the E2F sites. We also find that although there are multiple E2F sites in these promoters, a single intact E2F binding site is sufficient for E1A-mediated induction, although not to the full wild-type level. These results thus demonstrate that a variety of cellular genes that possess E2F binding sites are subject to E1A trans activation. Moreover, since the products of most of these genes are likely critical for cellular proliferation, there are obvious consequences of this trans activation for cellular phenotype.

Adenovirus Early Proteins↗