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Biomedical subjects

D Shedd

Publications and source records attributed to D Shedd.

At least 19 recordsLinked to original sources
PubMed1995

Transmissible retrovirus in Epstein-Barr virus-producer B95-8 cells.

Epstein-Barr virus (EBV) released from the B95-8 marmoset cell line has served as a prototype for biologic and biochemical studies of EBV. Here we identify and characterize a retrovirus carried by many cultures of B95-8 cells. The experiments were stimulated by the isolation of a cDNA clone from B95-8 cells in which sequences from the EBV large internal repeat were linked to gag sequences similar to those of squirrel monkey retrovirus, human isolate, SMRV-H. However, among 413 amino acids predicted from the nucleotide sequence of the gag region of the B95-8 SMRV isolate there were 48 amino acid changes that distinguished this virus from SMRV-H originally isolated from a human lymphoid cell line by Oda et al. (1988, Virology 167, 468-476). Nucleic acid and antibody probes were developed for the B95-8 isolate of SMRV. Using such probes, we found that SMRV-B95-8 was readily transmissible, independent of EBV, as an infectious virus to human B and T cell lines. SMRV-B95-8 was highly fusogenic in the presence or absence of EBV. The ultrastructural appearance of the B95-8 retrovirus was characteristic of a type D retrovirus. Cells dually infected with EBV and SMRV-B95-8 did not demonstrate increased levels of lytic EB viral replication. SMRV-B95-8 did not by itself cause lymphocyte immortalization or enhance immortalization by EBV. Thus SMRV-B95-8 does not contribute to the major biologic properties of the B95-8 strain of EBV.

Amino Acid Sequence↗
PubMed1995

In situ breast carcinoma after treatment during adolescence for thyroid cancer with radioiodine.

We reviewed the courses of patients treated during childhood or adolescence for thyroid cancer to estimate the frequency of, and to identify possible risk factors for, the occurrence of second malignant tumors in this population. We identified all patients treated for thyroid cancer in a cohort of 1,406 pediatric cancer patients who were diagnosed prior to 20 years of age during the period January 1, 1960 through December 31, 1988 and who were treated at Roswell Park Cancer Institute. Twelve patients were treated for thyroid cancer, of whom nine were women. In situ breast carcinoma was diagnosed 25 and 26 years after diagnosis of thyroid cancer in two of four women treated with radioiodine. No new cancers were diagnosed in the five women treated with thyroidectomy only. Two of four women treated for thyroid cancer during adolescence with radioiodine, which is concentrated in the breast as well as other organs, developed in situ breast carcinoma. Review of a large cohort of adolescent female thyroid cancer patients treated with radioiodine is necessary to provide an accurate estimate of their risk of developing breast cancer. These patients must remain under medical surveillance throughout their lifetimes to facilitate prompt diagnosis of and early intervention for new conditions, such as the occurrence of breast cancer.

Adolescent↗
PubMed1995

Detection of human serum antibodies to the BFRF3 Epstein-Barr virus capsid component by means of a DNA-binding assay.

A novel assay for antibodies to an immunodominant component of the Epstein-Barr virus (EBV) capsid antigen (VCA) complex was developed by creation of a chimeric protein containing the DNA-binding domain of the yeast GAL4 protein fused to the capsid antigen encoded by the BFRF3 gene of EBV. GAL4-BFRF3 antigen fusion protein bound specifically to a duplex DNA oligonucleotide containing GAL4-binding sites. Antibodies to the antigen were revealed by retardation of the electrophoretic mobility of the DNA-protein complex. Antibodies to the BFRF3 component of VCA became detectable approximately 2 months after onset of infectious mononucleosis. Kinetics of the antibody response to BFRF3 were identical using supershift or immunoblotting assays. Concordance between the DNA-binding assay and the classical indirect immunofluorescence assay for antibody to VCA was 97%. The GAL4 epitope assay is applicable for detection of antibodies to many cloned gene products.

Antibodies, Viral↗
PubMed1994

Surgical variables affecting postoperative swallowing efficiency in oral cancer patients: a pilot study.

This study examined the correlation between swallow function at 3 months postoperatively and surgical variables including volume resected, flap volume, ratio of flap volume to volume resected, percentage of oral tongue, tongue base, and anterior and lateral floor of mouth resected, and whether or not the mandible was preserved in 30 surgically treated oral cancer patients. Swallows of measured amounts of liquid and paste (pudding) materials were examined videofluoroscopically. Nine measures of swallow function were completed for each swallow. A factor analysis of all swallow variables was done for liquid and for paste consistencies to determine whether one measure was statistically representative of all swallow measures. This analysis indicated that oral pharyngeal swallow efficiency (OPSE) represented all measures for both liquid and paste consistencies. Then the correlation between OPSE and surgical variables was defined. Only percentage of oral tongue and percentage of tongue base resected were significantly negatively correlated with OPSE. That is, OPSE decreased for both liquid and paste as percentage of oral tongue or percentage of tongue base resected increased. Results are discussed in terms of diet choices and surgical management.

Deglutition↗
PubMed1993

Speech and swallow function after tonsil/base of tongue resection with primary closure.

Speech and swallowing function was examined in 11 patients who underwent surgical resection of greater than 1 cm of tongue base, tonsil, and faucial arch with mandible resected on the side of the tumor and reconstruction by primary closure. Preoperatively and 1 and 3 months post-healing, high fidelity audio recordings were made of a 6- to 7-minute conversational speech sample, the sentence version of The Fisher Logemann Test of Articulation Competence was administered, and videofluoroscopic assessment of oropharyngeal swallow was conducted. All subjects exhibited changes in speech and swallowing function postoperatively, with little improvement during the study. Patients exhibited greatest difficulty on stop and fricative consonants and bolus propulsion. Comparison with patients who received anterior tongue and floor of mouth resections and distal flap reconstruction revealed consistently better speech performance by the tonsil/base of tongue patients, although the same phonemes were affected. Swallow function was equally affected in the two groups. Results are discussed in terms of locus of surgical resection, nature of reconstruction, and need for swallowing therapy.

Analysis of Variance↗
PubMed1992

A chimeric mouse/human anti-IL-2 receptor antibody with enhanced biological activities.

A chimeric mouse/human MAb against the human p55 IL-2R was constructed from Ig genes isolated from a mouse hybridoma cell line, designated AHT107. AHT107 binds to a different epitope on p55 than IL-2, and similar to observations made for other rodent anti-IL-2R antibodies that do not recognize the same or spatially related epitope as IL-2, murine AHT107 did not efficiently inhibit proliferation of T-lymphocytes in mitogen and MLR PBMC stimulation assays. In contrast, the chimeric AHT107 antibodies containing a human IgG-1 constant region had substantially more anti-proliferative activity than their murine IgG-I counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in the PBMC cultures. This conclusion was supported by our observation that F(ab')2 generated from the chimeric antibodies did not efficiently inhibit proliferation in the PBMC assays, and the chimeric antibodies did not inhibit proliferation of an antigen specific, IL-2 dependent human T-cell clone stimulated in the absence of PBMC.

Amino Acid Sequence↗
PubMed1992

Smoking, alcohol, dentition and diet in the epidemiology of oral cancer.

This matched case-control study was conducted in Western New York. The smoking, alcohol consumption, dental hygiene and diet of 290 cases were compared with those of 290 sex-, age-, and neighbourhood-matched controls. The results confirm earlier findings that cigarette smoking and alcohol consumption impart substantial risk of oral cancer. The results also confirm that poor oral hygiene increases the risk of oral cancer, although this effect is much smaller than those of cigarette smoking and alcohol consumption. The results suggest that, of macronutrients, intake of fat is more likely than those of protein or carbohydrate to be related to risk. Of micronutrients, calcium, sodium, riboflavin and retinol are associated with risk, while thiamin, niacin, and dietary fibre are associated with decreased risk. Although patterns of dietary effects are discernable, these effects are in general much weaker than are those of smoking and alcohol consumption.

Aged↗
PubMed1992

Differential effects of a murine and chimeric mouse/human anti-interleukin-2 receptor antibody on human T-cell proliferation.

The preference for interleukin-2 receptor (IL-2R) expression on activated, compared with resting T lymphocytes makes the IL-2R a promising target for selective immunosuppressive therapy. To increase the potential therapeutic effectiveness of anti-IL-2R monoclonals, a chimeric mouse/human variant was constructed from Ig genes isolated from a murine anti-human IL-2R hybridoma cell line, designated AHT54. AHT54 binds to the same or spatially related epitope as IL-2 on the p55 protein that constitutes the low- and high-affinity forms of IL-2R. Although the murine and chimeric AHT54 antibodies inhibited cell-surface binding of IL-2 to the same extent, the chimeric antibodies containing a human IgG1 constant region had substantially more anti-proliferative activity than their murine IgG1 counterparts. Our results indicated that the human constant region of the chimeric antibodies interacted more efficiently than the murine constant region with effector components present in peripheral blood mononuclear cells (PBMC).

Animals↗
PubMed1986

Deletion mutants that affect expression of Epstein-Barr virus nuclear antigen in COS-1 cells after gene transfer with simian virus 40 vectors containing portions of the BamHI K fragment.

We have identified sequences that affect the efficient expression of Epstein-Barr virus nuclear antigen (EBNA 1) when the structural portion of its gene, found within the 2.9-kilobase-pair BamHI/HindIII fragment called Ilf, is expressed from a simian virus 40 vector. A set of nested deletions at the BamHI end of the fragment was constructed by using BAL 31 digestion, the addition of linkers, and ligation into pSVOd. The mutants were tested for their ability to express antigen in COS-1 monkey cells by using indirect immunofluorescence and immunoblotting. Deletion endpoints were determined by DNA sequencing of the 5' ends of the mutants. The deletion mutants could be subclassified into four groups based on their ability to express EBNA polypeptide. Mutants that retain more than 106 base pairs upstream from the start of the open reading frame in Ilf exhibit antigen expression indistinguishable from that of wild type. Mutants that invade the structural gene by 1,115 or more bases destroy antigen expression. Mutants that alter the splice acceptor site or invade the open reading frame by a short distance make antigen at a markedly lower frequency. There are three mutants, whose deletions map at -78, -70, and -44 base pairs upstream of the open reading frame, that make reduced levels of EBNA. Since these three mutants differ in the extent to which EBNA expression is impaired, the data suggest that there are several critical regions upstream of the open reading frame that regulate EBNA expression in COS-1 cells. It is not known whether these regulatory sequences, which would be located in an intron in the intact genome, play any role in the expression of EBNA in infected lymphocytes.

Animals↗
PubMed1984

Identification of Epstein-Barr nuclear antigen polypeptide in mouse and monkey cells after gene transfer with a cloned 2.9-kilobase-pair subfragment of the genome.

A new antigenic polypeptide was identified in mouse L cells and in monkey COS-1 cells in which Epstein-Barr nuclear antigen (EBNA) was expressed as the result of gene transfer with cloned fragments of Epstein-Barr virus (EBV) DNA. The same-size protein (Mr, approximately equal to 78,000) was seen in stably transformed mouse cells harboring only the BamHI K fragment [approximately equal to 5.2 kilobase pairs (kbp)] or its BamHI/HindIII subfragment, I1f (approximately equal to 2.9 kbp). Thus, the latter DNA fragment is sufficient to code for the protein. In transfected COS cells, a deletion mutant of the I1f fragment (approximately equal to 2.3 kbp) gave rise to a truncated protein (Mr, approximately equal to 52,000), whereas the BamHI K fragment yielded a full-sized Mr 78,000 species. This finding indicates that EBNA is encoded by viral genes. In Burkitt lymphoma lines or in immortalized lymphocytes, variation in the size of the I1f fragment correlated with the apparent molecular weight of the EBNA polypeptide. EBNA is truncated in two Burkitt lymphoma lines, Raji (Mr, 67,000) and P3JHR-1 (Mr, 70,000), which have deletion mutant I1f genes. EBNA in human lymphoid cells bearing a complete I1f fragment as part of the entire EBV genome is the same size (Mr, 78,000) as EBNA found after gene transfer of I1f alone into mouse or monkey cells. Therefore, these expression systems make an authentic EBNA after transfer of the appropriate EBV genes.

Animals↗
PubMed1984

Expression in COS-1 cells of Epstein-Barr virus nuclear antigen from a complete gene and a deleted gene.

In a previous study the BamHI-K fragment of Epstein-Barr virus DNA was shown to induce a nuclear antigen, Epstein-Barr virus nuclear antigen (EBNA), when cotransfected with the herpes simplex virus thymidine kinase gene into mouse LTK- cells. We have now inserted the BamHI-K fragment and a BamHI/HindIII subfragment, I1f , into shuttle vectors containing the origin of replication of simian virus 40. These plasmids have been introduced into COS-1, which are monkey kidney cells transformed by an origin-defective simian virus 40 genome. This expression system permitted rapid characterization of antigens, mRNAs, and proteins related to EBNA. The same-sized EBNA protein (approximately 78,000) was made after transfection with BamHI-K (5.2 kilobase pairs [kbp]) or the I1f subfragment (2.9 kbp). A deletion of about 600 bp occurred when the I1f fragment was propagated on the pSV2 plasmid in Escherichia coli. The deleted fragment gave rise to a smaller protein (approximately 52,000). These data provide evidence that EBNA is encoded by the 2.9-kbp I1f and is not an induced cellular protein. Nuclear antigen and polypeptide expression occurred equally well when the Epstein-Barr virus DNA was cloned on PSV2 -gpt or pSVOd . The latter plasmid lacks sequences allowing for efficient early gene transcription as well as splicing and polyadenylation signals which are present in pSV2 . Preliminary mapping of the EBNA gene transcripts demonstrated that two mRNAs (2.9 and 2.4 kilobases [kb]) are homologous to the I1f fragment. Taken together, the data suggest that the 2.9-kbp I1f fragment contains the structural gene for EBNA synthesis. COS-1 cells will thus provide a valuable system in which to analyze functional domains of the EBNA gene.

Animals↗
PubMed1983

Two Epstein-Barr viral nuclear neoantigens distinguished by gene transfer, serology, and chromosome binding.

We recently identified, by means of cotransformation of LTK- cells, a region of the Epstein-Barr virus (EBV) genome (the BamHI K fragment) that encodes or induces an EBV nuclear neoantigen (EBNA) serologically related to the EBNA found in lymphoid cells carrying the entire EBV genome. We now find that a second EBV DNA fragment, BamHI M, is also able to give rise to cotransformed LTK- cells with stable expression of a nuclear antigen. The BamHI K and M fragments have no apparent DNA homology. Many human sera that are reactive to EBNA in Raji cells detect both antigens; however, certain anti-EBNA-positive human sera are discordant and react only with the BamHI M or only with the BamHI K nuclear antigen. Every Raji cell appears to express both "M" and "K" antigens; D98 Raji cells, a somatic cell hybrid, express only "K" antigen. The K antigen is found on metaphase chromosomes of LTK cells and Raji cells. The M-induced antigen is not located on chromosomes when the cells are in metaphase but is present as granules within the nucleus.

Animals↗
PubMed1983

Use of cloned probes to detect Epstein-Barr viral DNA in tissues of patients with neoplastic and lymphoproliferative diseases.

Cloned fragments of the Epstein-Barr virus (EBV) genome were used to examine tissues from 145 patients for the presence of EBV DNA by two techniques: (1) nucleic acid hybridization of cell spots from which the DNA had been extracted in situ and (2) hybridization of DNA that had been transferred to nitrocellulose by Southern blotting. EBV DNA was found in tissues from four adults and five children with American Burkitt's lymphoma, infectious mononucleosis, lymphoma following bone marrow transplant, central nervous system lymphoma, nasopharyngeal carcinoma, and fatal polyclonal B-cell lymphoma following mononucleosis; two patients also had chronic pneumonitis, failure to thrive, and abnormal immune function. Six of the nine patients whose tissues contained EBV DNA had a demonstrable or presumed associated immunologic disorder. EBV DNA was not found in normal tissues or in a variety of hematologic neoplasms and other disorders. Nucleic acid hybridization methods can be used for the routine examination of the association of EBV with lymphomas and other lymphoproliferative syndromes occurring in immunodeficient individuals.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Association between primary hyperparathyroidism and previous irradiation.

The association between primary hyperparathyroidism and previous irradiation was investigated in two study groups. Among 36 patients with hyperparathyroidism, 4 (11%) knew of having received radiation therapy. In the second group of 323 patients with a history of radiation exposure and nodular thyroid disease, 4 (1%), thus far, were found to have hyperparathyroidism.

Acne Vulgaris↗
PubMed1982

Automatic encoding of clinical narrative.

An experiment in the automatic encoding of English-language medical data is described. The encoding program has two stages. First, the free-text input is parsed and the information is arranged in a tabular format by a general-purpose natural language processor developed at New York University. Then a simple code-dependent subprogram assigns numerical values to the entries on the basis of the positions the input words occupy in the information format. Results of a blind test of the encoding program using the code employed at Roswell Park Memorial Institute for earliest symptoms of head-neck cancer are presented.

Data Collection↗
PubMed1982

Stable expression in mouse cells of nuclear neoantigen after transfer of a 3.4-megadalton cloned fragment of Epstein-Barr virus DNA.

All cells that harbor the Epstein-Barr virus (EBV) genome contain a neoantigen in the nucleus (EBNA). By transfection we located a segment of the genome that encodes or induces an antigen serologically related to EBNA. The responsible genes are found in the 3.4-megaldalton BamHI fragment K of EBV DNA, specifically in the left 1.9 megadaltons represented by HindIII fragment I1. Mouse LTK- cells were cotransformed with recombinant plasmids, containing the herpes simplex virus thymidine kinase gene and either EcoRI fragment B or BamHI fragment of K of EBV DNA. The TK+ cells surviving in selective medium were cloned. About 50% of the clones expressed the neoantigen in every nucleus. These mouse cells were used as antigens in immunofluorescence tests. Antibody to the nuclear antigen was found in 30 human sera known to contain antibody to EBNA; it was not detected in 18 sera that did not have antibody to EBNA. Mouse cells expressing EBNA as the result of acquisition of cloned EBV DNA fragments should prove useful in the characterization of the structure of this antigen and as reagents for the diagnosis of EBV infections.

Animals↗