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D L Williams

Publications and source records attributed to D L Williams.

At least 271 records · Page 15Linked to original sources
PubMed1987

Structure, evolution, and regulation of chicken apolipoprotein A-I.

A full-length cDNA clone for the precursor form of chicken liver apolipoprotein A-I (apoA-I) was isolated by antibody screening of a chicken liver cDNA library in the expression vector lambda gt11. The complete nucleotide sequence and predicted amino acid sequence of this clone is presented. The identity of the clone was confirmed by comparison with partial amino acid sequences for chicken apolipoprotein A-I. Chicken preproapolipoprotein A-1 consists of an 18-amino acid prepeptide, a 6-amino acid propeptide, and 240 amino acids of mature protein. The sequence of the protein is homologous to mammalian apoA-I and is highly internally repetitive, consisting largely of 11-amino acid repeats predicted to have an amphipathic alpha-helical structure. The sequence of the propeptide (Arg-Ser-Phe-Trp-Gln-His) differs in two positions from that of mammalian apoA-I. The mRNA for chicken apoA-I is about 1 kilobase in length and is expressed in a variety of tissues including liver, intestine, brain, adrenals, kidneys, heart, and muscle. This quantitative tissue distribution has been determined and is similar to that observed for mammalian apoE and different from that of mammalian apoA-I mRNA. This reinforces the concept that avian apoA-I performs functions analogous to those of mammalian apoE. Moreover, comparisons revealed sequences of chicken apoA-I similar to the region of mammalian apoE responsible for interaction with cellular receptors. Previous studies have demonstrated striking changes in the rates of synthesis of apoA-I in breast muscle during development and in optic nerve after retinal ablation. We now demonstrate that these changes are paralleled by changes in mRNA levels. ApoA-I mRNA levels increase approximately 50-fold in breast muscle between 14 days postconception and hatching and then decrease about 15-fold to adult levels. The levels of apoA-I mRNA increase about 3-fold in optic nerve following retinal ablation. ApoA-I mRNA is also found in the brain in the absence of nerve injury. This may indicate that locally synthesized apoA-I has a routine or housekeeping function in lipid metabolism in the central nervous system.

Amino Acid Sequence↗
PubMed1987

Malignant lymphoma of the skin in children.

The clinical and histopathologic findings in eight cases of malignant lymphoma of the skin in children are presented. All patients had skin lesions as a primary manifestation of the disorder. Three patients had simultaneous regional lymph node involvement documented by the findings of subsequent biopsies. The majority (five patients) had solitary nodules involving the skin of the head and neck region. Three of the skin biopsy specimens were classified as lymphoblastic lymphoma, two large cell lymphoma, two mixed small and large cell lymphoma, and one small cleaved cell lymphoma. Disseminated disease subsequently developed in four patients in an interval that ranged from 4 to 30 months after diagnosis. The follow-up period ranged from 8 to 56 months, and median survival was 56 months. A literature review of 33 previously reported patients and our eight patients indicate that: skin of the head and the neck region is the most common site of involvement (56%); the majority of lymphomas are diffuse (93%); lymphoblastic lymphoma is the predominant type (53%), with a high proportion showing a non-T-cell phenotype; Burkitt's lymphoma and Hodgkin's disease of the skin are extremely rare; and most patients presented in an early clinical stage (Stage IE 56%, Stage IIE 21%), and prolonged disease-free survival was seen mostly in Stage I patients. The cumulative probability of survival for Stage I patients at 24 months was 0.71; while for Stages II to IV patients combined, it was 0.33 at 26 months.

Adolescent↗
PubMed1987

In vitro tumoricidal activity of resting and glucan-activated Kupffer cells.

Kupffer cells compose 80-90% of fixed tissue macrophages and have been suggested to play an important role in hepatic antitumor resistance. In the present study, the ability of resting and activated Kupffer cells to lyse syngeneic mammary adenocarcinoma BW10232 cells was evaluated. Activated Kupffer cells were isolated from C57Bl/6J mice following single of multiple intravenous (IV) injections of glucan (0.45 mg/mouse), a potent macrophage-activating agent. Mice receiving 5% (w/v) dextrose served as control. Resting Kupffer cells induced significant (P less than .05) 4% and 12% specific lysis of adenocarcinoma cells at target:effector ratios of 1:10 and 1:50, respectively. Kupffer-cell-mediated tumoricidal activity was depressed on day 1 following a single IV injection of glucan. By day 3 postglucan, the antitumor activity of Kupffer cells returned to control levels and was enhanced on days 5 and 10. Following multiple IV injections of glucan on days -5, -3, and -1, Kupffer-cell-mediated cytotoxicity was elevated on days 1 and 4. These observations demonstrate that resting Kupffer cells are significantly cytotoxic to adenocarcinoma cells at T:E ratios of 1:10 and 1:50 and following a transient inhibition of Kupffer-cell-mediated tumoricidal activity, glucan was effective in significantly enhancing the antitumor activity of Kupffer cells.

Adenocarcinoma↗
PubMed1987

Multiple telomeric associations of a trisomic whole q arm of chromosome 1 in a child with acute lymphoblastic leukemia.

The results of cytogenetic analysis of bone marrow cells from a 13-year-old boy with acute lymphoblastic leukemia (ALL) are described. Initial analysis of aspirated bone marrow disclosed ALL FAB-L1 morphology, common (Ia+, cALLa+) immunophenotype and a complex abnormal karyotype. The majority of leukemic cells showed unbalanced translocations that resulted in complete trisomy of the long arm of chromosome #1 as the common denominator. The heterochromatic region of chromosome #1 (1qh) was associated with the telomeres of whole chromosomes #2, #13, and #16 in 28% of the 36 metaphases completely analyzed. Telomeric association is a very rare event and this is only the second known report of its occurrence associated with ALL wherein the 1qh region is attached to the telomeres of different chromosomes, resulting in trisomy of the whole 1q arm.

Adolescent↗
PubMed1987

Enhancement of interleukin-1 and interleukin-2 production by soluble glucan.

Soluble glucan, a beta-1,3-linked polyglucose, is a biologic response modifier effective in the therapy of experimental neoplasia, infectious diseases and immunosuppression. Interleukin-1 (IL-1) and interleukin-2 (IL-2) are endogenous immunomodulators which are essential for effective immune responsiveness. In view of its broad spectrum of immunobiological activity, the ability of glucan to enhance the production of IL-1 and IL-2 was evaluated. Splenic IL-1 and IL-2 secretion as well as plasma IL-1 and IL-2 levels were determined in Sprague-Dawley rats receiving glucan (100 mg/kg, i.p.) at intervals ranging from 12 days to 1 h prior to collection of splenocytes and plasma. Glucan (100 mg/kg) was also injected either s.c., i.p. or i.v. on days -4, -3 and -2 prior to harvesting splenocytes on day 0. Splenic macrophage IL-1 production was initially elevated 12 h following glucan injection and was maintained for a 5 day period. IL-2 secretion by splenic lymphocytes was enhanced 6 h post-glucan and remained elevated for an additional 9 days. Plasma IL-1 activity was elevated 12 h post-injection, while IL-2 activity in plasma was enhanced at 1 h post-glucan. Peak IL-1 and IL-2 activity in plasma occurred 9 and 12 days, respectively, following glucan administration. With regard to route of administration, IV glucan was most effective in inducing lymphokine production. This study demonstrates that: (1) glucan will enhance IL-1 and IL-2 production and (2) elevations in lymphokine production can be maintained up to 12 days post-glucan.

Animals↗
PubMed1987

Regulation of chicken apolipoprotein B: cloning, tissue distribution, and estrogen induction of mRNA.

Apolipoprotein (apo) B is a major protein component of plasma very low-density and low-density lipoproteins (VLDL and LDL, respectively) and serves as a recognition signal for the cellular binding and internalization of LDL by the apoB/E receptor. In contrast to the situation in mammals, avian apoB is also a component of specialized VLDL particles that are produced by the liver in response to estrogen. These particles transport cholesterol and triglyceride from the liver to the ovary for deposition in egg yolk. We report here the identification and characterization of cDNA clones for chicken apoB and their use in examining the tissue distribution and hormonal regulation of chicken apoB mRNA. The cDNA clones were identified by immunological screening of a phage lambda gt11 library constructed with hen liver mRNA and their identity was supported by sequence comparisons with mammalian apoB. The chicken apoB mRNA is approximately the same size as mammalian apoB mRNA (14 kb), and, as occurs in mammals, is present at high levels in liver and small intestine. Unlike mammals, the chicken apoB mRNA is also found at high levels in the kidney, consistent with previous protein biosynthetic studies. A DNA-excess solution-hybridization assay was used to quantitate apoB mRNA in these tissues and to examine its hormonal regulation. In control roosters the liver and kidney contained 65% and 10%, respectively, as much apoB mRNA as the small intestine. Within 24 h after estradiol administration, apoB mRNA was increased five- to seven-fold in liver but was unchanged in intestine and kidney. The increase in apoB mRNA content and the kinetics of induction parallel hepatic apoB synthesis, indicating that estrogen regulates apoB production through changes in the cellular abundance of apoB mRNA. The apoB mRNA increased rapidly following hormone treatment while the mRNA for another VLDL protein (apoII) showed a lag or slow phase of several hours before significant mRNA accumulation occurred. These data indicate that the liver can respond immediately to estrogen to increase apoB mRNA accumulation, while apoII mRNA accumulation appears to involve additional events or signals which occur slowly and are specific to this gene.

Amino Acid Sequence↗
PubMed1987

Regulation of actomyosin ATPase activity by troponin-tropomyosin: effect of the binding of the myosin subfragment 1 (S-1).ATP complex.

In our model of regulation, the observed lack of cooperativity in the binding of myosin subfragment 1 (S-1) with bound ATP to the troponin-tropomyosin-actin complex (regulated actin) is explained by S-1.ATP having about the same affinity for the conformation of the regulated actin that activates the myosin ATPase activity (turned-on form) and the conformation that does not activate the myosin ATPase activity (turned-off form). This predicts that, in the absence of Ca2+, S-1.ATP should not turn on the regulated actin filament. In the present study, we tested this prediction by using either unmodified S-1 or S-1 chemically modified with N,N'-p-phenylenedimaleimide (pPDM X S-1) so that functionally it acts like S-1.ATP, although it does not hydrolyze ATP. We found that, in the absence of Ca2+, neither S-1.ATP nor pPDM X S-1.ATP significantly turns on the ATPase activity of the regulated complex of actin and S-1 (acto X S-1). In contrast, in the presence of Ca2+, pPDM X S-1.ATP binding almost completely turns on the regulated acto.S-1 ATPase activity. These results can be explained by our original cooperativity model, with pPDM X S-1.ATP binding only approximately equal to 2-fold more strongly to the turned-on form than to the turned-off form of regulated actin. However, our results are not consistent with our alternative model, which predicts that if pPDM X S-1.ATP binds to actin in the absence of Ca2+ but does not turn on the ATPase activity, then it should also not turn on the ATPase activity in the presence of Ca2+.

Actomyosin↗
PubMed1987

Expression of the murine apolipoprotein E gene is coupled to the differentiated state of F9 embryonal carcinoma cells.

Apolipoprotein E (apoE) expression was studied in F9 embryonal carcinoma cells that differentiate in response to retinoic acid into cells resembling either parietal endoderm or visceral endoderm of the parietal or visceral yolk sac. F9 cells secreted newly synthesized apoE when incubated with radiolabeled amino acid. Upon differentiation to parietal endoderm-like cells, apoE synthesis and secretion were markedly down-regulated. In contrast, apoE secretion was up-regulated upon differentiation to visceral endoderm-like cells. These changes in apoE expression were due, at least in part, to regulation of apoE mRNA abundance since visceral endoderm-like cells contained 5- to 7-fold more apoE mRNA than parietal endoderm-like cells. The apoE phenotype reflected the differentiated state of the F9 cell since either the up-regulated or down-regulated pattern was stable to the removal of the retinoic acid inducer. To determine how well apoE regulation in F9 cells reflects regulation in visceral and parietal yolk sacs, apoE mRNA was measured in yolk sac tissues of the 12-day mouse embryo. Visceral yolk sac contained 109 +/- 11 pg of apoE mRNA per micrograms of RNA while parietal yolk sac contained 14.3 +/- 3.1 pg/micrograms of RNA. This 7- to 8-fold difference is similar to the difference in the apoE mRNA contents of visceral endoderm-like and parietal endoderm-like F9 cells. RNA gel blot analysis showed that apoE mRNA is the same size in F9 cells as in yolk sac tissues and fetal or adult liver. In addition, primer-extension analysis showed that transcription is initiated at or near the same site on the apoE gene in F9 cells and mouse tissues. These data suggest that both quantitative and qualitative features of apoE gene expression in development are retained in the F9 cell. The F9 cell should provide a useful system to study the developmental activation of endogenous apolipoprotein genes as well as exogenous apolipoprotein genes introduced by transfection.

Animals↗
PubMed1987

Cyclosporine in the treatment of red cell aplasia.

A 4-year-old girl was diagnosed to have pure red cell aplasia. For 5 years, she received multiple packed red cell transfusions (average 11/year). Several therapeutic maneuvers were attempted including prednisone, oxymethalone, plasmaphoresis, high dose methyl prednisolone-to no avail. Finally, cyclosporine was administered for 5 months. This increased her reticulocyte count and cured the disease. For the last 2 years she has been in excellent health and has not required any further transfusions. The possible mechanism of action of cyclosporine in this disease is discussed.

Child, Preschool↗
PubMed1987

An analysis of leukemic cell chromosomal features in infants.

Leukemic cell chromosomal findings in 27 infants were analyzed. Among the 18 cases of acute nonlymphoblastic leukemia (ANLL), all but two were classified as monocytic or myelomonocytic. The remaining nine cases were acute lymphoblastic leukemia (ALL), seven lacking the common ALL antigen and two having cytoplasmic immunoglobulin (pre-B phenotype). Twenty-five cases (93%) had an abnormal karyotype, 21 (84%) being pseudodiploid. Chromosomal translocations were detected in 67% of the ANLL cases and in 78% of the ALL cases. Nonrandom chromosomal abnormalities included the t(9;11)(p21-22;q23) in three cases of monocytic leukemia, inversion of chromosome 16 in three cases of myelomonocytic leukemia with bone marrow eosinophilia, and t(4;11)(q21;q23) in one case of ALL. Chromosomal regions preferentially involved in infant leukemia included 11q23-25 (13 cases), 9p21-22 and 10p11-13. All but one of the 24 cases with chromosomal breakage or rearrangement had breakpoints that corresponded to known fragile sites, half of which were at 11q23-25, a finding that may have pathogenetic importance. The CALLA- or pre-B phenotype and the presence of chromosomal translocations in most infants with ALL provide a biological explanation for their poor prognosis.

Acute Disease↗
PubMed1987

Clinical and biologic hallmarks of the Philadelphia chromosome in childhood acute lymphoblastic leukemia.

Of 366 children with acute lymphoblastic leukemia (ALL) in whose bone marrow cells complete G-banding of chromosomes was successful, translocations were present at diagnosis in 141 (38.5%). The Philadelphia (Ph) chromosome was identified in 18 of these cases (4.9%). Features closely associated with the presence of the Ph chromosome were older age (median, 7.9 years), high leukocyte count (median, 47.3 X 10(9)/L), French-American-British L1 blast cell morphology, high incidence of CNS leukemia at diagnosis, and the common ALL immunophenotype. All patients were treated according to modern chemotherapeutic regimens for ALL used at our institution. Complete remissions were successfully induced in only 13 (72%) of the 18 patients with Ph + ALL, and only six remain free of leukemia for periods of 7+, 9+, 10+, 13+, 49+, and 70+ months. Our findings confirm the association of the Ph chromosome with classic high-risk features of ALL in children and suggest that this abnormality confers a very poor prognosis that has not yet been improved by modifications in established therapeutic regimens.

Acute Disease↗
PubMed1987

Hypodiploidy is associated with a poor prognosis in childhood acute lymphoblastic leukemia.

Leukemic cells from 31 (7.6%) of 409 children with newly diagnosed acute lymphoblastic leukemia (ALL) had a hypodiploid karyotype. The patients' ages ranged from 0.8 to 17 years (median, 5 years) and their initial leukocyte counts from 1.0 to 132 X 10(9)/L (median, 12.7 X 10(9)/L). Modal chromosome numbers for the leukemic stem lines were 45 in 26 cases, 28 in two cases, and 26, 36 and 43 in one case each. Seven cases had one to three additional abnormal lines due to clonal evolution. Chromosome 20 was lost most frequently (nine cases). Structural abnormalities--including chromosomal translocations (21 cases), deletions (ten cases), duplications (two cases), or inversions (one case)--were common findings; the nonrandom translocations consisted of the t(1;19)(q23;p13.3) in two pre-B cases and tdic(9;12)(p1?1;p1?2) in three cases of common ALL. When compared with hyperdiploid cases (greater than 50 chromosomes), ALL with hypodiploidy was found to have a poorer outcome and was more likely to be associated with chromosomal translocations, higher serum lactic dehydrogenase levels, and age less than 2 or greater than or equal to 10 years. Moreover, patients with hypodiploid ALL fared as poorly as those with pseudodiploid karyotypes, even though their leukocyte counts and serum lactic dehydrogenase levels were lower and they had a comparable frequency of leukemic cell translocations. Hypodiploidy is therefore an unfavorable karyotypic feature in childhood ALL.

Acute Disease↗
PubMed1987

7q32-q36 translocations in childhood T cell leukemia: cytogenetic evidence for involvement of the T cell receptor beta-chain gene.

Blast cell chromosomal rearrangements involving the long arm of chromosome 7 were identified in eight of 197 cases of childhood acute lymphoblastic leukemia (ALL). Breakpoints were variable but tended to cluster in either the proximal or the terminal 7q region, depending on the immunophenotype of the cells. The 7q32-q36 region, the locus of the T cell receptor beta-chain gene, was the site of breakpoints in four of 31 cases of T cell ALL but was not involved in any of the 166 cases originating from B cell precursors (P less than .0004). In three of the four T cell cases it was possible to identify the chromosomal segment that had been translocated to the 7q32-q36 region: 1p32, 2p21, and 6p21. The 1p32 and 6p21 bands are particularly interesting, as they contain the sites of two known protooncogenes, c-L-myc and hpim, respectively. Our findings suggest that the locus of the beta-chain gene of the T cell receptor is a preferential site for certain chromosomal rearrangements in leukemic T lymphoblasts, analogous to the T cell receptor alpha-chain gene on human chromosome 14. Translocation of proto-oncogenes to a site near the beta-chain regulatory sequences provides a potential mechanism for oncogene activation.

Adolescent↗
PubMed1987

tdic(9;12): a nonrandom chromosome abnormality in childhood B-cell precursor acute lymphoblastic leukemia: a Pediatric Oncology Group Study.

In a review of 432 children with newly diagnosed acute lymphoblastic leukemia (ALL), we identified a new nonrandom translocation, tdic(9;12)(p1?1;p1?2), in the leukemic marrow cells of eight patients. Seven had hypodiploid karyotypes that lacked chromosomes 9 and 12 and contained a der(12), tdic(9;12); the eighth had a pseudodiploid karyotype with two normal 9 chromosomes, one normal 12 and the der(12), tdic(9;12). Abnormalities involving chromosomes other than 9 and 12 were noted in four of the eight patients. All cells with the tdic(9;12) expressed both the common ALL antigen and HLA-DR. Cytoplasmic immunoglobulin, a marker of pre-B ALL, was detected in one case with the tdic(9;12) but was absent in the other seven. Our results suggest that the tdic(9;12)(p1?1;p1?2) rearrangement is specifically associated with leukemic B cell precursors.

B-Lymphocytes↗
PubMed1986

The application of glucose oxidase-labeled antibodies for the detection of proteins on nitrocellulose.

We have evaluated the sensitivity of immunostaining with glucose oxidase for the detection of monomeric human serum albumin (HSA) and monomeric human immunoglobulin G (IgG). A modification of a histochemical procedure was utilized by replacing phenazine methosulfate (PMS) with 1-methoxyphenazine methosulfate (mPMS) and by replacing Tris-HCl with Tris-citrate to improve the solubility of the tetrazolium compounds tested. mPMS is less sensitive to light, and may be stored for long periods in solution; it is now used routinely by histochemists in place of PMS in dehydrogenase cytochemistry. pH values of 6.3-8.3 were tested, with the reaction at pH 8.3 providing a slight increase in sensitivity. The reaction rate increased markedly as the pH became more alkaline. The minimum quantity of HSA detected was 3 ng applied directly to nitrocellulose and 10 ng when blotted. Human IgG was routinely detected at 250 pg and occasionally at 100 pg when dotted on the nitrocellulose.

Collodion↗
PubMed1986

Induction of rat E and chicken A-I apolipoproteins and mRNAs during optic nerve degeneration.

Apolipoprotein synthesis was measured in control optic nerves and optic nerves undergoing Wallerian degeneration. After short term organ culture with radiolabeled amino acid, optic nerve extracts were reacted with antiserum to rat or chicken apolipoproteins. Immunoprecipitates were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the degenerating rat optic nerve, apo-E synthesis increased from 0.30 to 0.90% of newly synthesized protein and from 0.45 to 1.4% of secreted protein. A DNA-excess solution hybridization assay was constructed to measure the absolute amount of apo-E mRNA in control and degenerating optic nerves. Paralleling the increase in apo-E protein synthesis, the absolute amount of apo-E mRNA was elevated 3- to 4-fold after enucleation. Similar to rat apo-E, apo-A-I synthesis was increased in degenerating chicken optic nerve. Chicken apo-A-I represented 0.65 and 3.5% of newly synthesized protein from control and enucleated optic nerves, respectively. Apo-A-I increased from 0.85 to 5.5% of secreted protein following enucleation. Using in vitro translation to quantitate relative amounts of chicken apo-A-I mRNA, enucleated optic nerve apo-A-I mRNA content was increased 5-fold. These results suggest that local apolipoprotein synthesis may be involved in the mobilization of myelin cholesterol which occurs during Wallerian degeneration. The similar response of the rat and chicken to increase optic nerve apolipoprotein synthesis during degeneration supports the idea that avian peripheral apo-A-I and mammalian peripheral apo-E may be performing functions common to both classes of animals.

Animals↗
PubMed1986

Delay in the diagnosis of pediatric brain tumors.

The interval from the onset of symptoms to the diagnosis in 79 children with primary brain tumors was compared with that in 45 children with Wilms' tumor and 123 children with acute leukemia. The patients with brain tumors had a significant delay from symptom onset to diagnosis. Only 38% of primary brain tumors were diagnosed within the first month after the onset of symptoms. In contrast, 84% of Wilms' tumors and 80% of cases of acute leukemia were diagnosed within one month of the onset of symptoms. Early detection of brain tumors is important as it may have a significant bearing on clinical outcome.

Acute Disease↗