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Biomedical subjects

D L Williams

Publications and source records attributed to D L Williams.

At least 325 records · Page 18Linked to original sources
PubMed1984

New chromosomal translocations correlate with specific immunophenotypes of childhood acute lymphoblastic leukemia.

Cytogenetic analysis of leukemic cells obtained at diagnosis from 122 patients with childhood acute lymphoblastic leukemia (ALL) disclosed chromosomal translocations in 36 cases. Two new nonrandom translocations were identified and found to be associated with specific immunophenotypes of the disease. The first, identified in 4 of 16 cases of T-cell ALL positive for sheep erythrocyte receptors (E+), involved the short arm (p) of chromosome 11 and the long arm (q) of chromosome 14 and was designated t(11;14) (p13;q13). The second, found in 7 of 23 cases with a pre-B-cell phenotype, involved the long arm of chromosome 1 and the short arm of chromosome 19; it was designated t(1;19) (q23;p13.3). A third abnormality involving a common breakpoint on chromosome 12 (band p 12) was also identified. These two new differentiation-specific translocations suggest a mechanism for aberrant expression of genes that influence lymphoid cell growth and development, as well as leukemogenesis.

Adolescent↗
PubMed1984

A direct bone marrow chromosome technique for acute lymphoblastic leukemia.

We describe a direct bone marrow chromosome technique that was developed especially for use in studies of acute lymphoblastic leukemia (ALL). The features responsible for technical improvements include: the use of RPMI 1640 medium, supplemented with 30% fetal calf serum, to support cellular activity during both specimen transport and Colcemid treatment; the processing of only 0.1 ml of sedimented cells or less per centrifuge tube; the exposure of cells to Colcemid for a maximum of 25 min; control of the total time of exposure to hypotonic solution; the use of a steel wire as a stirring rod (fashioned to fit the centrifuge tube) for mixing cells; slide preparation by a specific edging-flaming technique; the natural aging of the slides to achieve optimal drying; and the use of a modified G-banding procedure that employs Wright's stain. This technique has been used in more than 350 cases of ALL and has consistently provided analyzable banded chromosomes, even in hyperdiploid cases with up to 91 chromosomes. It makes the previously recognized morphological difference between metaphases of residual normal cells and those from the leukemic clone less apparent. The edging-flaming technique of slide preparation is the most important component and is especially appropriate for spreading large numbers of chromosomes in ALL.

Bone Marrow↗
PubMed1984

Modification of post-operative C. albicans sepsis by glucan immunostimulation.

Glucan, a beta-1,3 polyglucose, was evaluated for its ability to enhance resistance of post-operative mice to experimentally induced C. albicans sepsis. Male C57BL/6J mice were injected i.v. with glucan (0.45 mg/mouse) on days 10,7,4 and 1 prior to midline laparotomy and intravenous challenge with 3 X 10(6) C. albicans. The detrimental effect of surgery on survival following C. albicans infection was manifested by a 47% survival in the non-surgery-infected group in contrast to 20% in the surgery-infected group. Protection against C. albicans was observed in the glucan-treated groups. The glucan-treated non-operated mice manifested 100% survival while the surgery group had a 73% survival. Glucan significantly enhanced macrophage phagocytic function in control and operated mice. Laparotomy alone did not significantly depress macrophage phagocytosis. Histopathological studies revealed that glucan markedly inhibited the renal pathology associated with C. albicans challenge both in the presence and absence of laparotomy. These data indicate that glucan increased survival and reduced renal pathology associated with C. albicans challenge in the post-operative period. These observations suggest that Biologic Response Modifiers such as glucan may be effectively employed in patients who are at risk for post-operative infections.

Adjuvants, Immunologic↗
PubMed1984

Steroids. 2. Synthesis of C-18 functionalized steroids via the Smith-Hughes route.

The total synthesis of a series of racemic C-18 functionalized steroids was carried out in a search for novel estrogen-and/or progestin-receptor agonists or antagonists. The target compound 3,18-dihydroxyestra-1,3,5(10)-triene (2), 13-(2-oxopropyl)gona-4-en-3-one (3), 13-(1-hydroxy-1-prop-2-ynyl)gona-4-en-3-one (4a and 4b) and 13-(1-acetoxy-2-oxo-1-propyl)gona-4-en-3-one (5) are position isomers of the highly biologically active estradiol, progesterone, norethindrone, and 17-acetoxyprogesterone, respectively. Nevertheless the synthetic C-18 functionalized steroids 3-5 showed little activity in the Clauberg and anti-Clauberg assays. Compound 2 showed no antagonism in the postcoital assay despite the fact that it exhibited weak but measurable in vitro receptor-binding activity.

Animals↗
PubMed1984

Auer rods in mature granulocytes: a unique morphologic feature of acute myelogenous leukemia with maturation.

The authors observed Auer rods in mature neutrophils, bands, and metamyelocytes in two children with AML with maturation (FAB M2). In order to determine if this rare finding was characteristic of AML M2, the authors reviewed the bone marrows and peripheral blood smears of 50 children with AML M2 and 50 children with other AML subtypes (FAB M1, M3, M4, and M5). They found Auer rods in mature neutrophils and band forms in 10 of 50 patients (20%) with AML M2 but in none of 50 patients with non-M2 AML. This finding was not related to the frequency of mature cells in the specimen or to the frequency of Auer rods in blasts. Cytogenetics did not show a consistent abnormality. The presence of Auer rods in mature granulocytes is unique to FAB M2 AML in the authors' series and supports the concept that in AML at least some of the mature myeloid cells are involved in the leukemic process.

Adolescent↗
PubMed1984

Analysis of the non-ionic detergent-soluble lipids of human stratum corneum.

Mechanical stimulation of the skin surface in the presence of non-ionic detergent (Triton X-100)-containing buffers has been used to prepare isolated corneocytes and non-ionic detergent-soluble (NIDS) material from human stratum corneum. Analysis of the major lipid classes present in the corneocytes and NIDS material has been performed by thin layer chromatography with flame ionization detection and quantitation based on the introduction of an internal standard. Results indicate that the NIDS lipid represents a disproportionately large amount of the total stratum corneum lipid and that it differs in composition from the corneocyte lipid, there being a greater proportion of the cholesteryl ester fraction in the corneocytes. Both these findings support the 'brick wall' model of the stratum corneum and provide further evidence that the NIDS material is intercellular in nature.

Chromatography, Thin Layer↗
PubMed1984

Acute leukaemia with mixed lymphoid and myeloid phenotype.

Three children with acute leukaemia had blasts that expressed both lymphoid and myeloid markers. The blasts met immunological criteria for acute lymphoblastic leukaemia (ALL)--common ALL antigen+, HLA-DR+, terminal deoxynucleotidyl transferase+--but their cytochemical features, including positive myeloperoxidase and Sudan black B, were those of acute nonlymphoblastic leukaemia (ANLL) as defined by the French-American-British Group. 30% of the blasts from one of two patients tested reacted with a monoclonal antibody specific for nonlymphoid cells (MCS-2). The wide overlap in the percentages of blasts expressing lymphoid or myeloid markers indicates that some leukaemic cells in each child had a mixed phenotype. There were no consistent cytogenetic findings, and the Philadelphia chromosome was not present. Complete remission was induced by treatment effective for either ALL (two patients) or ANLL. These three cases appear to represent a rare leukaemia subtype that we have designated acute leukaemia with mixed lymphoid and myeloid phenotype. Its recognition may be important in treatment, since two patients achieved remission with standard therapy for ALL. These cases demonstrate further the phenotypic heterogeneity that may be seen in leukaemic cell differentiation.

Acute Disease↗
PubMed1984

Evidence for clonal evolution in pre-B-cell leukaemia.

This case study provides evidence for clonal evolution in pre-B-cell leukaemia. At diagnosis, the lymphoblasts from a 3-year-old boy were morphologically subtyped as L1 (French-American-British classification). Their immunophenotype was CALLA+, CIgM+, SIg-, TdT+, and the karyotype was pseudodiploid with a 1;19 translocation. Striking shifts were apparent when the child relapsed 16 months later. The morphologic subtype had changed to L3, CALLA and TdT had disappeared, and a consistent karyotype was lacking. The modal chromosome number had increased through clonal evolution to 85, the 1;19 translocation was retained, and a new marker, a 14q+ (partial duplication) appeared and was present in a majority of cells. These cytogenetic findings are characteristic of a transforming state. However, despite the loss of TdT, the appearance of classic L3 morphology and the acquisition of a 14q+ marker, the cells retained a predominantly pre-B phenotype.

Antigens, Neoplasm↗
PubMed1984

Global and regional left ventricular function and tomographic radionuclide perfusion: the Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial.

The Western Washington Intracoronary Streptokinase In Myocardial Infarction Trial enrolled 250 patients with acute myocardial infarction. After the coronary angiographic diagnosis of thrombosis, patients were randomly assigned to receive either conventional therapy with heparin or intracoronary streptokinase followed by heparin. Of the 232 patients who survived at least 60 days, 207 (89%) underwent radionuclide ventriculographic determination of global and regional ejection fraction at a single institution at 62 +/- 35 days after infarction. In the first 100 patients, infarct size was also determined by quantitative single-photon emission tomographic imaging with thallium-201 (201Tl) and expressed as a percentage of the left ventricle with a perfusion defect. Overall, global ejection fraction did not differ between patients treated with streptokinase (45.9 +/- 13.9%; n = 115) and control patients (46.1 +/- 14.4%; n = 92, p = NS). Similarly, the regional posterolateral, inferior, and anteroseptal ejection fraction did not differ between the two groups. Infarct size as measured by 201Tl tomography was 19.4 +/- 12.8% (n = 52) of the left ventricle for the streptokinase group and 19.6 +/- 11.8% (n = 48; p = NS) for the control group. When patients were compared within groups by electrocardiographic location of infarction, time to treatment, or the presence or absence of vessel opening, there were no significant differences between streptokinase and control patients. Statistical inclusion of the 18 patients who died early and were unavailable for study also failed to modify the results, except for a possible reduction in inferior infarct size as measured by 201Tl tomography.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

Quantitation of size of relative myocardial perfusion defect by single-photon emission computed tomography.

The purpose of this study was to validate a semiautomatic method for quantitating the size of relative myocardial perfusion defects from single-photon emission computed tomographic (SPECT) images. We compared the size of the image defect in vivo, expressed as percent of involved left ventricle, as determined by this method with the anatomic size of the defect in vitro in 19 dogs. To test the method under optimal conditions, we first labeled the left ventricular myocardium in nine dogs by left atrial injection of 99mTc-labeled macroaggregated albumin particles after acute occlusion of one coronary artery. The "defect volume" was defined as the volume of the left ventricular myocardium for which counts fell 2 or more SDs below the distribution of counts in the myocardium supplied by a normal coronary artery in a series of animals. The relative in vivo defect volume by SPECT occupied 26.46 +/- 12.7% of the left ventricular volume (mean +/- SD), compared with a relative defect size in vitro of 33.3 +/- 13.7% (p = NS) of left ventricular volume as determined by well counting of myocardial samples. There was a close correlation between the two measurements (r = .92). However, myocardial relative defect volumes involving less than 5% of myocardium were not identified by SPECT. The defect volume weighted for the relative reduction in flow within the defect zone or the relative "reduced perfusion volume" was also determined. The correlation between the estimates by SPECT and those made in vitro for relative reduced perfusion volume was also high (r = .94).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1984

Simultaneous occurrence of terminal deoxynucleotidyl transferase and myeloperoxidase in individual leukemia blasts.

Cases of acute leukemia showing both terminal deoxynucleotidyl transferase (TdT) and myeloperoxidase (MPO) activities are usually classified as acute myelogenous leukemia (AML). Although some reports have implied overlap of TdT and MPO based on population percentages, direct evidence for simultaneous expression of TdT and MPO by a leukemic blast is lacking. By use of a simple new technique developed in our laboratory for identifying TdT and MPO in individual cells by light microscopy, we examined three cases of acute leukemia with both TdT and MPO positivity and found that the incidence of cells positive for both TdT and MPO was 0%, 1%, and 23%. Cytogenetic analysis showed a single leukemic clone in all patients, providing additional evidence that these leukemias arose from a single cell capable of expressing both MPO and TdT. These findings have implications for understanding the relation between MPO and TdT expression in leukemia.

Adolescent↗
PubMed1983

Comparison of the effects of tropomyosin and troponin-tropomyosin on the binding of myosin subfragment 1 to actin.

The effect of tropomyosin alone on the binding of myosin subfragment 1 (S-1) to actin was compared to that of troponin-tropomyosin, with and without Ca2+. Over a range of ionic strength and with different ligands (adenyl-5'-yl imidodiphosphate, pyrophosphate, and adenosine 5'-diphosphate), tropomyosin confers slight cooperativity to the binding of S-1 to actin. In the presence of Ca2+, troponin does not affect the cooperative action of tropomyosin alone. In addition, troponin-tropomyosin and tropomyosin alone are also identical in their ability to strengthen the binding of S-1-ligand to actin 3-fold and the binding of S-1 alone to actin 7-fold, at high levels of saturation of the actin with S-1. Although troponin does not significantly affect the cooperative action of tropomyosin alone in the presence of Ca2+, it does markedly enhance the cooperativity in the binding of S-1 to actin in the absence of Ca2+.

Animals↗
PubMed1983

Differential responsiveness of avian vitellogenin I and vitellogenin II during primary and secondary stimulation with estrogen.

Avian vitellogenin consists of two major species, VTG I and VTG II, which show major differences in structure and immunological properties suggesting that VTG I and VTG II are distinct gene products. During primary stimulation with estrogen, VTG I was found to accumulate in plasma much more slowly than VTG II. At 1 day after hormone treatment VTG I was only 1-3% of VTG II, but by day 5 VTG I increased to approximately 25% of VTG II. Measurements of hepatic vitellogenin synthesis confirmed the slower induction and reduced expression of VTG I. A further difference was noted in the amnestic or memory response to secondary estrogen treatment. Measurements of VTG I and VTG II accumulation and synthesis after primary and secondary estrogen treatment showed that the memory response occurs to a much greater extent for VTG I than VTG II. These differences indicate that the inductions of VTG I and VTG II are not tightly coupled.

Animals↗
PubMed1983

Non identity of non ionic detergent soluble (NIDS) protein and stratum corneum autoantigens.

The relationship between naturally occurring circulating stratum corneum autoantibodies and experimentally produced antibodies to a non ionic detergent soluble (NIDS) protein fraction from human stratum corneum has been investigated. Using indirect immunofluorescence and indirect haemagglutination techniques, anti NIDS protein serum was shown not to inhibit the autoantibody-antigen reaction. Furthermore no direct interaction could be demonstrated between sheep red blood cells coated with stratum corneum autoantigen and anti NIDS protein serum. The NIDS protein antigens therefore represent a separate and distinct class of stratum corneum antigens.

Antibodies↗
PubMed1983

Role of tyrosine in the acute effects of ethanol on rat brain catecholamine synthesis.

Acute ethanol administration exerts multiple effects on rat brain catecholamine synthesis, associated with corresponding changes in cerebral tyrosine concentration. Catecholamine synthesis is enhanced at 1 hr by an increased availability of circulating tyrosine to the brain after inhibition of liver tyrosine aminotransferase activity. Tyrosine hydroxylation in vivo and tyrosine hydroxylase activity measured in vitro are also enhanced at 1 hr. Catecholamine synthesis is inhibited at 2-4 hr when tyrosine availability to the brain is decreased because of an enhancement of liver tyrosine aminotransferase activity. Serum neutral amino acid concentrations are decreased at 5 hr. This is followed 1 hr later by normalization of cerebral catecholamine synthesis. By 8 hr after ethanol administration, the latter becomes enhanced because of increased cerebral uptake of tyrosine. Catecholamine synthesis is inhibited at 12 hr because of enhanced transamination of brain tyrosine. Tyrosine metabolism finally returns to normal at 16 hr after ethanol administration. These results are discussed in relation to previous work with ethanol, and to central and peripheral mechanisms of regulation of brain catecholamine synthesis.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

Cytogenetic features of acute nonlymphoblastic leukemia in 73 children and adolescents.

We examined the leukemia cells of 81 consecutively admitted children and adolescents with acute nonlymphoblastic leukemia (ANLL) to determine the frequency and specificity of chromosomal abnormalities. Karyotypes were obtained for 73 (90%) of the 81 children, and 36 (49%) were abnormal. The modal karyotypes for the cases were tightly clustered in the diploid range; only 5 (7%) were hypodiploid, with 45 chromosomes each, and only 2 (3%) had greater than 50 chromosomes. Specific chromosomal abnormalities in the abnormal karyotypes were compared to morphologic subgroups of ANLL. An 8;21 translocation was found in 6 of 9 cases with M2 morphology but was also found in 1 case with M1 morphology. One of 4 with M3 (progranulocytic) morphology had a 15;17 translocation, and another had a 17q deletion. A structural abnormality in 11q was found in 3 of 7 patients with M5 (monoblastic) morphology, 2 of whom had a 9;11 translocation. The only case of M6 had a 22q-or Philadelphia chromosome in addition to other abnormalities. Statistical analysis of 27 abnormal karyotypes showed preferential structural rearrangement of 8q and 21q. We conclude that, in children as well as adults, specific structural abnormalities are correlated with certain morphologic subgroups of ANLL. However, other chromosomal changes associated with prior mutagenic exposure of adult ANLL were uncommon in children, which may suggest a difference in pathogenesis.

Acute Disease↗