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Biomedical subjects

D L Williams

Publications and source records attributed to D L Williams.

At least 289 records · Page 16Linked to original sources
PubMed1986

Effect of retinoic acid on myeloid antigen expression and clonal growth of leukemic cells from children with acute non lymphocytic leukemia--a Pediatric Oncology Group Study.

We have used a panel of 5 monoclonal antibodies against normal myeloid-differentiation antigens to determine retinoic acid-induced changes in cell surface antigens on ANLL bone marrow cells from 24 children at the time of diagnosis. Two of these antibodies (T5A7 and 5F1) detect antigens expressed on normal mature granulocytes and on all monocytes, respectively. The percentage of positive cells for each monoclonal antibody was determined by indirect immunofluorescence. After 5 days incubation with 1 microM RA in liquid culture, cells from 11 of 24 patients showed substantially increased expression of one or both antigens detected by T5A7 and 5F1. Leukemic bone marrow cells from these patients were also cultured in methylcellulose medium with and without 1 microM RA for one week, and cells from 16 of 24 patients showed clonal growth. Cultures from 10 of these 16 patients showed RA-induced inhibition of colony growth; of these 10 patients, cultures from six patients showed RA-induced increases in antigens associated with maturing myeloid cells. This suggests that the RA-induced inhibition of clonal growth observed with leukemic cells from these patients may be accompanied by the increased expression of maturation-associated myeloid antigens by these cells in the presence of RA.

Acute Disease↗
PubMed1986

Unfavorable presenting clinical and laboratory features are associated with CALLA-negative non-T, non-B lymphoblastic leukemia in children.

Twenty-four (5.7%) of 424 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have blast cells that expressed HLA-DR antigens but not the common ALL antigen (CALLA), E-rosette receptors, T-cell antigens, or cytoplasmic or surface immunoglobulins. Each of the eight cases tested expressed the B-cell associated antigen B4, but not B1 or B2 antigen. Myeloid-associated antigens were not present in any of the 10 cases tested. By comparison with common (CALLA+ B-cell precursor) ALL, patients having this immunophenotype were more likely to be children less than 2 yr of age (p less than 0.001), to have higher initial leukocyte counts (p less than 0.001), and to have blast cells with a DNA index less than 1.16 (p = 0.05), a pseudodiploid karyotype (p = 0.01) and a chromosomal translocation (p = 0.003). The presence of any chromosomal translocation in these CALLA- ALL was related to measures of increased leukemic cell burden including higher leukocyte counts, larger liver and spleen sizes and higher serum lactic dehydrogenase levels. While the patients were entered into several treatment arms of two protocols, the CALLA- cases appeared to have lower remission rate (p = 0.06) and shorter event-free survival time (p = 0.05) than did those with common ALL. The association with clinical and laboratory features of known adverse prognostic significance provides some explanation for the poor treatment outcome of CALLA- ALL.

Antigens, Neoplasm↗
PubMed1986

Enrichment of T lymphocytes from bovine peripheral blood mononuclear cells using an immuno-affinity depletion technique ("panning").

A simple and efficient method to enrich bovine T lymphocytes from peripheral blood mononuclear cells (PBMC) by immuno-affinity depletion ("panning") has been developed. The PBMC were initially separated by density gradient centrifugation on Histopaque of density 1.077 g/ml. The T lymphocyte subset was then separated from PBMC by depletion of membrane immunoglobulin (Ig) bearing cells which had an affinity for anti-Ig antibodies bound to polystyrene tissue culture flasks. An average of 95% of the nonadherent "panned" cells were identified as T lymphocytes using a label of peanut agglutinin conjugated with fluorescein isothiocyanate (PNA-FITC). Two percent of the PNA negative cells were Ig bearing cells. The average yield was 50% of the original T lymphocytes found in the PBMC population, and the cell viability as assessed by trypan blue exclusion was greater than 95%. The separation took approximately 2 hours, and the total number of T lymphocytes recovered from 40 ml of blood was in the range of 20-40 X 10(6).

Animals↗
PubMed1986

A Community-wide epidemic of hepatitis A in Ohio.

Between June 1, 1983 and August 30, 1984, an epidemic involving 313 cases of hepatitis A occurred in Muskingum County, Ohio. One hundred ninety-seven cases occurred in the city of Zanesville, with 34.7% of cases concentrated in two neighborhoods in the eastern part of the city. Case characteristics were similar to those reported in previous community-wide outbreaks, including a maximum attack rate among 5-9-year-olds and a very low attack rate in adults over 30 years. Case households were larger, and their members were less educated than the mean for households in the city. Forty-eight per cent of the cases reported exposures to other cases which temporally could have been the source of infection. A case-control study failed to show differences in several behavioral factors between case and control households, but did confirm that lower socioeconomic status was a risk factor for the disease. Broad use of immunoglobulin was effective in preventing clinical disease among family contacts, but did not stop the outbreak. This outbreak typifies a genre of hepatitis A epidemic transmitted from person to person in which exact routes of spread are poorly understood and control is difficult. Lower socioeconomic status may be a marker for some unidentified behaviors that promote hepatitis A transmission.

Adolescent↗
PubMed1986

Biologic and prognostic significance of the presence of more than two mu heavy-chain genes in childhood acute lymphoblastic leukemia of B precursor cell origin.

We examined the arrangement of the mu heavy-chain immunoglobulin (Ig) genes in the leukemic blast cell DNA of 93 children with acute lymphoblastic leukemia (ALL). All cases met morphologic and cytochemical criteria for ALL, lacked detectable T cell surface antigens, and expressed HLA-DR (Ia) antigens. Eighty-three of the 93 patients (89%) were positive for the common acute lymphoblastic leukemia antigen (CALLA), and 20 of 91 (22%) tested had detectable cytoplasmic immunoglobulin. As expected, the heavy-chain lg gene was rearranged in all cases, and the pattern of rearrangements was variable; 23 had one allele rearranged and one in the germ line configuration; 15 had one rearranged and one deleted; and 37 had two rearranged. Unexpectedly, in 18 patients the presence of more than two mu gene-hybridizing bands was detected. Combinations of enzymes and heavy-chain gene probes were used to confirm that the extra bands were not the result of underdigestion of the DNA or DNA restriction site polymorphism. In eight of the 18 patients, we identified an extra chromosome 14 as a possible cause of the extra bands' hybridizing to the mu heavy-chain constant-region probe. In the remaining ten patients, the presence of three or four bands hybridizing with the mu probe suggests the presence of two populations of leukemic cells that may have arisen either by separate leukemic transformation events or by clonal evolution of one clone into two related lines. Although preliminary (2-year follow-up), our data suggest that childhood ALL of B lineage with more than two mu heavy-chain genes, but without extra copies of chromosome 14, may be more resistant to therapy.

Adolescent↗
PubMed1986

Cytogenetic features and serum lactic dehydrogenase level predict a poor treatment outcome for children with pre-B-cell leukemia.

Leukemic cells from 89 (24%) of 369 children with newly diagnosed acute lymphoblastic leukemia (ALL) were found to have a pre-B immunophenotype. By comparison with blasts having the common ALL phenotype, the pre-B cells were more likely to have a DNA index less than 1.16 (P = 0.02), a pseudodiploid karyotype (P less than 0.001), and a chromosomal translocation (P = 0.001). Increased serum lactic dehydrogenase levels (P = 0.001) were also characteristic of pre-B ALL; otherwise, the clinical and laboratory features of the two groups were similar. A nonrandom chromosomal translocation, t(1;19)(q23;p13.3), was identified in blast cells from 16 (23%) of the 70 patients with pre-B ALL and adequate chromosome banding studies; different translocations were found in 11 of the remaining patients. The presence of any chromosomal translocation in the pre-B group was significantly related to a higher leukocyte count, an increased level of serum lactic dehydrogenase, an increased percentage of S-phase cells, black race, and a blast cell DNA index less than 1.16. Four presenting features were found to confer an increased risk of treatment failure among pre-B patients: pseudodiploidy, chromosomal translocation, black race, and higher serum lactic dehydrogenase level. In a multivariate analysis, pseudodiploidy emerged as the strongest factor for predicting relapse in pre-B ALL. The frequent association of chromosomal abnormalities of known adverse prognostic significance and high serum lactic dehydrogenase levels with pre-B-cell ALL explains, at least in part, the poor treatment outcome reported for children with this subtype of leukemia.

Adolescent↗
PubMed1986

Chromosomal translocations play a unique role in influencing prognosis in childhood acute lymphoblastic leukemia.

Certain types of chromosomal abnormalities have been shown to exert strong independent influence on treatment outcome in acute lymphoblastic leukemia (ALL). To identify the changes most closely associated with prognosis, we analyzed the completely banded blast cell karyotypes of 161 children with this disease. One hundred twenty-five cases had one or more chromosomal abnormalities, with 45 showing translocations. The frequency of translocations was highest (58%) among patients with pseudodiploid karyotypes and lowest (0%) in the hyperdiploid group defined by 51 or more chromosomes. During the maximum 6-year follow-up period, 30 of the 45 patients with a translocation failed therapy, compared with only 27 of the 116 who lacked this feature. Life-table estimates of event-free survival indicate that only 14% of the translocation group will be in complete remission at 3 years. The percentages of failures associated with random and nonrandom translocations were virtually identical (68% v 65%). When entered in a Cox proportional hazards model with seven other types of chromosomal abnormalities, and then with 11 clinical and laboratory variables of known prognostic value in ALL, translocation emerged as the strongest single predictor of treatment outcome (P less than 0.0001). The model indicated that translocation increases the risk of treatment failure six times by comparison with the absence of this feature. These findings offer an explanation for the majority of early treatment failures in childhood ALL, including those previously attributed to ploidy classification.

Child↗
PubMed1986

Nonrandom involvement of the 12p12 breakpoint in chromosome abnormalities of childhood acute lymphoblastic leukemia.

We studied the presenting clinical and biologic features of 23 children with acute lymphoblastic leukemia (ALL) whose leukemic marrow karyotypes contained abnormalities involving the short arm of chromosome 12. Nineteen of the abnormalities were assigned to the 12p12 breakpoint. The median age of the children was 5 years (range 2 to 13 years) and their initial leukocyte counts ranged from 1,800 to 424,000/microL (median 30,000/microL). Twenty-one patients (91%) had common phenotype ALL (CALLA+, HLA-DR+), including three cases with a pre-B cell phenotype (CIg+). The remaining two cases were T cell in origin. The French-American-British (FAB) morphologic type of lymphoblastic leukemia was L1 in all cases but one. With a median follow-up of 11 months, four patients have relapsed and another failed induction therapy. The modal chromosome number in all cases was less than 50. Three distinct cytogenetic patterns, with apparently similar clinical manifestations, were noted: terminal deletions of chromosome 12 in 10 cases, apparently balanced reciprocal translocations in 6, and unbalanced translocations in 7. All translocations were between the 12p arm and different donor chromosomes except for chromosomes 7, 9, and 17, which participated twice. Only two patients had identical translocations: t(7;12)(q11;p12). This unusual variation in donor chromosomes and breakpoints suggests that translocations involving the 12p are specific with respect to only one member of the translocation pair, namely chromosome 12. The relatively high frequency of the 12p abnormalities in this study (10% of all completely banded cases seen over a 35-month period) warrants further investigation.

Adolescent↗
PubMed1986

Comparison of the in vitro cytolytic effect of hepatic, splenic and peritoneal macrophages from glucan-treated mice on sarcoma M5076.

Our previous results have demonstrated that glucan will significantly modify the course of syngeneic murine tumors. Additionally, results denote that glucan increases macrophage-mediated lysis of syngeneic tumor cells. The present study was undertaken to more closely examine the effect of parenteral glucan administration on the tumoricidal activity of hepatic, splenic and peritoneal macrophage populations. C56B1/6J mice were injected intravenously with glucan (0.45 mg/mouse) on days 1,3,6,9,12 and 15. Hepatic, splenic and peritoneal macrophages were isolated on days 8, 12 and 16. The macrophages were co-incubated for 72 h with syngeneic reticulum cell sarcoma M5076 at a target: effector ratio of 1:50. A significant increase in the cytolytic activity of all three macrophage populations was observed. Kupffer cell tumoricidal activity was increased (p less than 0.01) on day 8, but was not significantly different from control on days 12 and 16. Peritoneal exudate macrophages showed increased (p less than .001) tumoricidal activity on days 12 and 16, respectively. Splenic macrophages showed an enhanced (p less than 0.01) increase in lytic activity only on day 16. The present results indicate that: 1) glucan will enhance macrophage-mediated tumoricidal activity of three distinct macrophage populations and 2) a temporal relationship exists between glucan administration and expression of lytic activity by the macrophage populations. These observations further define the mechanism by which glucan exerts its potent anti-tumor activity.

Animals↗
PubMed1986

Cell-mediated immunity in healthy adults in Antarctica and the sub-Antarctic.

Cell-mediated immune responses were studied in 2 Antarctic and sub-Antarctic groups at quarterly intervals over a wintering year, using the cutaneous CMI Multitest. The sub-Antarctic population at Macquarie Island (M.I.) had levels of responsiveness and hypoergy comparable to other healthy populations in temperate regions. The Antarctic group at Mawson showed decreased scores and total number of positive responses to antigens, and a significantly elevated incidence of anergy and hypoergy. Quarterly skin testing showed considerable variability in subject responsiveness to specific antigens at different times over the year. However, only 2 antigens at M.I., trichophyton and proteus, showed a significant seasonal variation in score. There was no statistically significant seasonal variation in antigen scores at Mawson. It is concluded that environment and stress factors in Antarctic expeditions are responsible for the decreased immunological responsiveness.

Acclimatization↗
PubMed1986

Glucan stimulates production of antitumor cytolytic/cytostatic factor(s) by macrophages.

Glucan, a beta 1,3-linked polyglucose, is an effective macrophage activating and tumor-inhibitory agent. Previous studies indicate that glucan enhances macrophage-mediated tumoricidal activity. The present study was designed to examine the ability of glucan to enhance the production of tumor cell cytotoxic/cytostatic factor(s) designated, because of their macrophage origin, as macrophage cytotoxic factor(s) (MCF). Resting splenic macrophages in culture for 20 h secreted detectable levels of MCF. Coincubation of macrophages with bacterial endotoxin lipopolysaccharide (LPS) resulted in an enhancement of MCF production, compared to resting macrophages. Glucan-activated macrophages were more effective in producing MCF than both resting and LPS-activated macrophages. The MCF was cytotoxic to certain tumor cell lines at high concentrations and cytostatic at lower concentrations. The MCF was not significantly cytotoxic to N3T3 or BC/Sk murine fibroblasts, denoting specificity in response. Loss of MCF activity occurred following coincubation of macrophage culture supernatant with adenocarcinoma cells but not with normal fibroblasts. The MCF activity eluted at 38,000 and 84,000 daltons following column chromatographic analysis, and was heat labile at 100 degrees C but not 56 degrees C. In addition, MCF activity was diminished by protease inhibitors and antisera against tumor necrosis factor. Induction of MCF secretion may be an additional mechanism of glucan-induced antitumor activity.

Adenocarcinoma↗
PubMed1985

Locus of the alpha-chain of the T-cell receptor is split by chromosome translocation in T-cell leukemias.

Mouse lymphoma cells were hybridized with two human acute T-cell leukemias with a t(11;14) (p13;q11) translocation and the segregated hybrids were examined for the presence of the DNA segments coding for the constant (C) and the variable (V) regions of the alpha chain (C alpha and V alpha) of the T-cell receptor. The C alpha segment was translocated to the involved chromosome 11 (11p+) while the V alpha segment remained on the involved chromosome 14 (14q-). The data indicate that the locus for the alpha chain of the T-cell receptor is split by the chromosomal breakpoint between the V alpha and the C alpha gene segments, and that the V alpha segments are proximal to the C alpha segment within chromosome band 14q11.2.

Animals↗
PubMed1985

Secondary structure analysis of apolipoprotein II mRNA using enzymatic probes and reverse transcriptase. Evaluation of primer extension for high resolution structure mapping of mRNA.

Primer extension has been employed to locate sites of cleavage made in apolipoprotein II (apo-II) mRNA by structure-specific nucleases. This approach permits structural analysis of specific mRNAs within a complex population. Electrophoretic analysis of cDNAs synthesized from T1 RNase-treated and mock-treated apo-II mRNA revealed that most cleavage sites can be mapped with single nucleotide accuracy. However, some T1 RNase-dependent cDNAs demonstrated mobilities corresponding to one nucleotide longer than the mRNA template, suggesting that reverse transcriptase can add a single nucleotide to full-length cDNAs in a template-independent reaction. This approach has been used to map double-stranded and single-stranded accessible domains of the 3' noncoding region of apo-II mRNA with cobra venom, T1, and S1 ribonucleases. Cleavage profiles of apo-II mRNA renatured under a variety of buffer and temperature conditions were identical and in no case was overlap observed between sites of cleavage by double strand- and single strand-specific enzymes. These results suggest that apo-II mRNA possesses a predominant, stable secondary structure. A computer-generated structure model, consistent with these nuclease cleavage data, is presented. In addition to the analysis of mRNA higher order structure in mixed RNA populations, this approach also appears suitable for the analysis of protein-mRNA interactions. Termination sites of incomplete cDNAs produced when untreated or mock-treated RNA is used as a template for primer extension were also mapped. This analysis revealed an over-representation of termination at the dinucleotides CA and CU, suggesting that termination of some incomplete apo-II cDNAs is related to primary and not secondary structure. Such sequence dependence could reflect in vivo degradation by an endogenous cytidine-specific nuclease.

Animals↗