Search PubMed⌕ Search

Biomedical subjects

S D Smith

Publications and source records attributed to S D Smith.

At least 253 records · Page 14Linked to original sources
PubMed1987

Elimination of clonogenic malignant human T cells using monoclonal antibodies in combination with 2'-deoxycoformycin.

2'Deoxycoformycin (dCF) specifically inhibits adenosine deaminase (ADA) and causes selective cytotoxicity of normal and malignant T cells. In clinical trials, dCF caused rapid lysis of malignant T lymphoblasts. Although dCF has been associated with dose-limiting nonhematopoietic toxicities, myelosuppression has not been observed. Since dCF is relatively nontoxic to hematopoietic stem cells, we tested dCF for utility in the ex vivo purging of malignant T lymphoblasts from remission leukemic bone marrow for autologous bone marrow transplantation. We found that T lymphoblast cell lines were sensitive to dCF (plus deoxyadenosine [dAdo]) under conditions that did not ablate human hematopoietic colony-forming cells. Moreover, combined pharmacologic (dCF plus dAdo) and immunologic (anti-T cell monoclonal antibodies [McAb] plus complement) purging resulted in additive reduction in clonogenic T lymphoblasts. These results provide the basis for a clinical trial of bone marrow transplantation using combined pharmacologic/immunologic purging of T lymphoblasts from patients' harvested autologous marrow.

Antibodies, Monoclonal↗
PubMed1987

Discordant expression of CD3 and T-cell receptor beta-chain antigens in T-lineage lymphomas.

Using an immunoperoxidase technique that identifies both surface and cytoplasmic antigen expression, the authors examined 28 benign reactive lymphorproliferative lesions and 55 T-lineage lymphomas for reactivity with CD3 (Leu-4; T-cell receptor-associated antigen) and beta F1 antibodies, the latter recognizing nonpolymorphic determinants on T-cell receptor beta chains. Consistent with previous observations that these two antigens are co-expressed on the vast majority of thymocytes, peripheral blood T cells and tonsillar T cells, all 28 reactive lymphoproliferations showed essentially identical patterns of CD3 and beta F1 expression. In contrast, only 29 of 55 T-lineage lymphomas displayed coexpression of these antigens. Among 33 peripheral T-cell lymphomas, 11 cases showed CD3/beta F1 discordance (7 CD3+/beta F1-; 4 CD3-/beta F1+), and 5 showed absence of both these antigens. Nine of 22 T-lymphoblastic lymphomas showed CD3/beta F1 discordance (all CD3+/beta F1-), and 1 case was CD3-/beta F1-. These patterns of CD3/beta F1 expression, along with the patterns of CD2, CD4, CD5, CD7, and CD8 antigen expression in these neoplasms, indicate that T-cell lymphomas can manifest phenotypes not apparently reflective of normal T populations and suggest the presence of abnormal gene expression in these malignancies. The existence of aberrant phenotypes in T-cell neoplasia suggests caution in interpretation of investigations using T-lineage malignancies as models of normal T-cell biology. Finally, the identification of phenotypic abnormalities in T-lineage populations can be of great diagnostic usefulness in the delineation of benign versus malignant T-cell proliferations.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

New muscle growth in denervated extraocular muscle.

Current therapies for paralytic ocular motility disorders often provide less than satisfactory results. Promising new techniques of nerve grafting and muscle transplantation used to treat muscle paralysis elsewhere in the body may have application to the ocular motor system. In studying a procedure designed to reinnervate paretic extraocular muscle (e.o.m.), we produced not only the expected nerve growth but also abundant new muscle growth. A considerable amount of this muscle growth occurred within the axon depleted nerve fascicles of the paretic muscle, suggesting that this structure was a particularly good matrix for muscle fiber growth. These observations suggest that new, entire neuromuscular units may be induced to grow in the plane of a paretic muscle if appropriate surface characteristics can be established.

Animals↗
PubMed1986

Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation.

cDNAs for the bcl-2 mRNA were cloned from a human common acute lymphoblastic leukemia cell line. Nucleotide sequence analyses showed that the 6 kb bcl-2 mRNA potentially encodes a 26 kd protein that is homologous to a predicted Epstein-Barr virus protein. Most t(14;18) translocation breakpoints cluster within a narrow region of a 5.4 kb exon that contains a long 3'-untranslated region of the bcl-2 mRNA. As a result of t(14;18) translocation, hybrid bcl-2/immunoglobulin heavy chain transcripts are produced that consist of the 5' half of the bcl-2 mRNA fused to a "decapitated" immunoglobulin heavy chain mRNA. Nucleotide sequence analyses confirmed that the hybrid transcripts continue to encode a normal bcl-2 protein. Our results suggest that t(14;18) translocations alter expression of the bcl-2 gene both by transcriptional activation and by abnormal posttranscriptional regulation of bcl-2 mRNA.

Amino Acid Sequence↗
PubMed1986

Common mechanism of chromosome inversion in B- and T-cell tumors: relevance to lymphoid development.

An inversion of chromosome 14 present in the tumor cells of a patient with childhood acute lymphoblastic leukemia of B-cell lineage was shown to be the result of a site-specific recombination event between an immunoglobulin heavy-chain variable gene and the joining segment of a T-cell receptor alpha chain. This rearrangement resulted in the formation of a hybrid gene, part immunoglobulin and part T-cell receptor. Furthermore, this hybrid gene was transcribed into messenger RNA with a completely open reading frame. Thus, two loci felt to be normally activated at distinct and disparate points in lymphocyte development were unified and expressed in this tumor.

B-Lymphocytes↗
PubMed1986

Intellectual, behavioral, and linguistic characteristics of three children with 18p- syndrome.

Developmental characteristics of three girls with 18p- syndrome are described, with detailed history and results of psychological and speech/language evaluations completed at various ages. Results suggest that some children with 18p- syndrome have average abilities in selected areas, despite previous reports that these children have mild to severe mental retardation. Two of the three girls had more severe deficits in linguistic, as opposed to nonlinguistic, abilities. All had similar difficulties with speech articulation. It is suggested that children with speech/language delays who have physical features associated with this syndrome have chromosome analysis performed. It is also recommended that children identified as having 18p- syndrome be referred for comprehensive developmental assessments and remedial special education programming before a specific prognosis is determined.

Articulation Disorders↗
PubMed1986

Spelling errors in adults with a form of familial dyslexia.

We compared the spelling errors on the WRAT II made by adults (N = 24) with an apparent autosomal dominant form of dyslexia to those made by their normal adult relatives (N = 17) and by spelling-age matched normal controls (N = 17) using a computerized error evaluation program (SEEP). The normal adult relatives were significantly better than the dyslexics in both reading and spelling, but did not differ in age, education, or IQ. SEEP evaluated each error independently for both phonological and orthographic accuracy at 2 levels of complexity. Each level of complexity was analyzed separately using a 3 X 2 (group X dimension) analysis of variance. The main finding of interest was a significant group X dimension interaction effect at the complex level, which indicated that the dyslexics had a qualitatively different profile across the 2 dimensions than either normal group who had parallel profiles. The dyslexics performed like the younger normal group on the complex phonological dimension but like the adult normal group on the complex orthographic dimension. These results indicate a dissociation in this form of familial dyslexia between these 2 dimensions of spelling development, and suggest that these dyslexics may fit the subtype of dysphonetic or phonological dyslexia. The implications of these results for the underlying cognitive deficit in this form of dyslexia are discussed.

Adult↗
PubMed1986

Characterization of insulin, insulin-like growth factors I and II, and growth hormone receptors on human leukemic lymphoblasts.

Receptors for insulin, insulin-like growth factors I and II (IGF-I and IGF-II), and human GH were studied in 6 T- and 12 B-lymphoblast cell lines isolated from patients with lymphoid malignancies. These cell lines have been maintained in continuous culture with stable chromosome, immunophenotype, and enzyme characteristics for an 8- to 21-month period. Four of 6 T-cell lines expressed IGF-I, but not insulin, receptors. One T-cell line bound only insulin, and 1 T-cell line bound both hormones. Conversely, 9 of 12 B-cell lines had insulin, but not IGF-I, receptors. Two of these lines bound both hormones, and 1 line did not bind either hormone. IGF-II binding was less than 1.5%/10 million cells for all lines and was less than 1% for 13 of the 18 lines. Specific binding of GH was undetectable in all cell lines. Time, temperature, and pH dependence of peptide binding were characterized for the T-cell IGF-I receptor and the B-cell insulin receptor and were consistent with previously described models for these receptors. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cross-linked receptors revealed an apparent mol wt greater than 300K unreduced and a 130K binding subunit after dithiothreitol reduction for both the T-cell IGF-I and the B-cell insulin receptor. These cell lines thus provided a unique opportunity for the study of growth factor receptors in fully characterized clonal populations of human lymphoblasts. We conclude that specific receptors for IGF-I and insulin are present on T- and B-lymphoblasts; divergence of these receptors appears to be a characteristic of lymphoblasts, since T-cells preferentially expressed IGF-I receptors and B-cells expressed insulin receptors; and IGF-II binding was relatively low, while specific GH binding was undetectable on both T- and B-lymphoblasts. These results suggest that insulin and IGF-I may play a role in lymphocyte differentiation and metabolism.

Cell Line↗
PubMed1986

Solenoid surface coils in magnetic resonance imaging.

A nonplanar solenoidal surface radiofrequency coil is used as a receiver with a conventional transmitter coil in a magnetic resonance imaging system. The improved signal-to-noise ratio, compared with that of conventional fixed saddle or solenoid receiver coils, permits higher resolution imaging and thinner image sections. In addition, the problem of signal dropoff that occurs in deep structures with planar and other noncircumferential surface coils is eliminated. Solenoid surface coils are particularly useful in imaging deep structures in anatomic regions that do not fit standard head and body coils, such as the neck, knees, and other smaller body parts.

Adult↗
PubMed1986

Cytogenetic and immunophenotypic analysis of cell lines established from patients with T cell leukemia/lymphoma.

Cell lines were established from five patients with T cell malignancies. Two patients had T cell lymphoblastic lymphoma (T-LL), whereas three patients had T cell acute lymphoblastic leukemia (T-ALL). Both T-LL cell lines expressed cell surface antigens characteristic of midthymocytes (Leu 2, 3, 6+). One T-ALL cell line also expressed this immunophenotype, one expressed suppressor/cytotoxic antigens (Leu 2+; Leu 3, 6-), and one expressed antigens of a mature but uncommitted T cell (Leu 4+; Leu 2, 3, 6-). Cytogenetic analysis showed that each cell line had 46 chromosomes with pseudodiploidy. The three T-ALL cell lines had only a few chromosome changes; one cell line had one deletion, another had two deletions, and the third had a translocation and two deletions (including loss of part of 9p). In comparison, both T-LL cell lines had complex chromosome changes, including most notably a rearrangement of band 14q11.2. The immunophenotypes and chromosome breakpoints showed patterns of interlock between the T-LL and T-ALL cell lines because common abnormalities occurred at six distinct chromosome sites. Cell lines with limited and specific chromosomal abnormalities are important because they can provide the basic material for molecular genetic studies that could elucidate the genetic mechanisms involved in neoplasia.

Adolescent↗
PubMed1985

In vitro and in vivo chemotherapy screening of the divalent cation chelator 1,10-orthophenanthroline.

1,10-Orthophenanthroline (OP) is a divalent cation chelating agent with known cytotoxicity to human normal and malignant T-lymphocytes. To determine whether OP might be a useful anticancer agent with specific T cell toxicity, OP's effect on cell growth was determined on colony-forming cells. The assay used supported growth of both malignant lymphoid and normal myeloid colony-forming cells (CFU-C) and thus a direct comparison of OP's antilymphoid and antimyeloid toxicity was obtained. The malignant lymphoid cells tested were established from patients at relapse and were resistant to conventional chemotherapeutic agents in vitro. While OP was found to be toxic to all cells tested, some selective kill of malignant cells over CFU-C occurred. OP's cytotoxicity was time-dependent and a three-log enhanced kill occurred when the drug exposure time was increased from 1 to 24 h. When test cells were continously exposed to OP, the ID50 was less than 1 micrograms/ml for malignant lymphoid cells and the sensitivity index (SI = x ID50 CFU-C divided by x ID50 cell line) ranged from 1.5 to 3.0. The National Cancer Institute currently screens new compounds for antitumor activity by determining whether the test drug is toxic to a mouse lymphocytic leukemia cell line (P388). While the mouse P388 cells were sensitive to OP in vitro, no effect was seen when OP was administered in vivo, even when schedules designed to take advantage of OP's time-dependent toxicity were used. Since malignant cells were sensitive to OP (ID50 less than 1 micrograms/ml), and some selectivity over CFU-C occurred (SI greater than 1), OP may be a useful agent for control of leukemic cell growth in vitro. However, since OP did not control the growth of P388 cells in vivo, additional studies designed to enhance the therapeutic index of OP in vivo are needed.

Animals↗
PubMed1985

Fusion of an immunoglobulin variable gene and a T cell receptor constant gene in the chromosome 14 inversion associated with T cell tumors.

An inversion of chromosome 14, inv(14)(q11,q32), is frequently observed in human T cell tumors; the cytogenetic breakpoints are of interest because the T cell receptor alpha-chain and immunoglobulin heavy chain genes reside on chromosome bands 14q11 and 14q32, respectively. We have investigated the structure of the alpha-chain genes in a T cell line harboring the chromosome 14 inversion. On the normal chromosome 14, a V alpha segment has rearranged nonproductively with a J alpha segment. In contrast, the inverted chromosome features an unprecedented rearrangement in which an immunoglobulin heavy chain variable gene segment (VH) on chromosome band 14q32 has joined with a J alpha segment from band 14q11. The VH-J alpha C alpha rearrangement is productive at the genomic level and therefore may encode a hybrid immunoglobulin/T cell receptor polypeptide.

Alleles↗
PubMed1985

Phenotype of adult familial dyslexia: reading of visually transformed texts and nonsense passages.

Oral reading is less disrupted by mirror-image and upside-down text transformations for individuals affected by familial dyslexia than for non-affected readers. An analysis of errors made during oral reading of nonsense passages showed that most readers substituted real words for nonsense words, often of similar visual configurations. These findings were discussed in the context of what is known about cerebral functioning during reading. One interpretation of the present study is that affected readers used a reading strategy apparently mediated more by right than left hemisphere mechanisms, than did nonaffected readers.

Adolescent↗
PubMed1984

Common region on chromosome 14 in T-cell leukemia and lymphoma.

Chromosome 14 breakpoints in malignant human lymphocytes cluster on the long (q) arm near bands q11 and q32. An inversion of chromosome 14 due to breaks in q11.2 and q32.3 has now been found in a newly established childhood T-cell lymphoma cell line and confirmed in T-cell chronic lymphocytic leukemia. A translocation was also found between chromosomes 10 and 14 with a breakpoint at 14q11.2 in another T-cell lymphoma cell line. It is proposed that a proximal region on chromosome 14 in or near sub-band q11.2 is related to T-cell function. Rearrangements in this region may affect the growth of T lymphocytes and be involved in the development of T-cell malignancies.

Cell Line↗
PubMed1984

Management of children with isolated testicular leukemia.

Since 1975, nine children with testicular leukemia were treated at the University of Kansas Medical Center on a standard protocol. Six patients presented with overt testicular leukemia and three patients had microscopic testicular leukemia detected on a biopsy done after 3 years of continuous complete remission. All patients had an M1 bone marrow at the time of testicular relapse and one patient had a concomitant central nervous system (CNS) relapse. Therapy consisted of testicular irradiation, CNS chemoprophylaxis, and systemic reinduction chemotherapy. Systemic maintenance therapy after the testicular relapse consisted of 6-mercaptopurine and methotrexate with vincristine/prednisone pulses administered in the same basic dose and schedule as the patient's original maintenance regimen. These nine patients had a mean duration of first remission of 33 months and a mean duration of second remission of 45+ months. Four patients have relapsed (two bone marrow, one CNS, one CNS + bone marrow), but five patients remain in their second complete remission for 33+ to 94+ months from the time of testicular relapse. These results demonstrate that, in some children, testicular leukemia represents a site of temporary drug resistance and long-term second remissions can be obtained (once local disease is controlled) by using the initial maintenance chemotherapy regimen.

Antineoplastic Combined Chemotherapy Protocols↗