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Biomedical subjects

K Sullivan

Publications and source records attributed to K Sullivan.

At least 37 records · Page 2Linked to original sources
PubMed1989

Long term effects and quality of life in children and adults after marrow transplantation.

These studies of late effects associated with marrow transplant preparative regimens demonstrate the need for continued long-term follow-up of these patients. Sequential studies of growth and development in children demonstrate that few endocrine function abnormalities occur after high dose CY, but multiple endocrine abnormalities occur after TBI containing regimens. Children may have decreased growth rates and abnormal development of secondary teeth. Most young adult patients who received CY only have normal gonadal function recovery and may be fertile. Neuropsychological abnormalities, cataracts and secondary malignancies may also develop. Although the marrow transplant preparative regimen may not be the treatment modality solely responsible for the various observed abnormalities, transplant recipients need to be evaluated carefully for many years to determine onset of abnormalities and to initiate appropriate therapeutic interventions which may improve the quality of life of these unique patients.

Adult↗
PubMed1988

Cyclin mRNA and protein expression in recombinant interleukin 2-stimulated cloned murine T lymphocytes.

Expression of cyclin, a non-histone nuclear protein, during recombinant interleukin 2 (rIL2)-driven cell-cycle progression of cloned T lymphocytes has been assessed. We found that expression of cyclin protein, as detected by immunofluorescence, is tightly associated with proliferation, and not merely S-phase, of L2 cells stimulated with rIL2. Cyclin immunofluorescence was detected in all cell-cycle phases (G1/S/G2/M, as detected by flow cytometry) of proliferating L2 cells. Accumulation of cyclin mRNA levels was induced as early as 1 h after stimulation, was maximal at 25-49 h, and remained elevated throughout stimulation, as detected by Northern blot analysis. A cDNA-encoding murine cyclin was cloned from a cDNA library prepared from IL2-stimulated cloned T cells. The sequence of the 5' end of the murine cyclin cDNA was determined and found to be 88% and 82% similar to the sequences of cDNA clones encoding rat and human cyclin, respectively. The present studies demonstrate that cyclin protein and mRNA accumulation are highly regulated during IL2-induced proliferation of a cloned T cell. These data provide a framework for addressing the molecular mechanisms regulating cyclin gene expression during cellular proliferation.

Animals↗
PubMed1987

Autoantibody to the proliferating cell nuclear antigen neutralizes the activity of the auxiliary protein for DNA polymerase delta.

Two murine monoclonal antibodies to the proliferating cell nuclear antigen (PCNA), a rabbit anti-N-terminal peptide antibody and human auto-antibody to PCNA reacted with the auxiliary protein for DNA polymerase delta from fetal calf thymus following SDS-polyacrylamide gel electrophoresis, confirming the identity of PCNA and the auxiliary protein. Undenatured auxiliary protein was immunoprecipitated by the human autoantibody, but not by the monoclonal antibodies, which were raised to SDS-denatured PCNA, nor by the anti-N-terminal peptide antibody, suggesting that the epitopes recognized by both the monoclonal antibodies and the anti-peptide antibody are not exposed in the native protein. The human anti-PCNA autoantibody neutralized the activity of the auxiliary protein for DNA polymerase delta, but did not inhibit the activity of pol delta itself. The ability of pol delta to utilize template/primers containing long stretches of single-stranded template was inhibited by the anti-PCNA autoantibody, whereas the activity of pol alpha on such templates was not affected, confirming the specificity of the auxiliary protein for pol delta. The ability of PCNA, a cell cycle-regulated protein, to regulate the activity of pol delta suggests a central role for pol delta in cellular DNA replication.

Animals↗
PubMed1987

Proliferating cell nuclear antigen/cyclin is an interleukin 2-responsive gene.

Previously, we have shown that a protein designated p36 is synthesized at a high rate during interleukin 2-driven proliferation of a cloned T lymphocyte, L2. Biosynthesis of p36 increases 1000-fold during the initial mid-G1 phase of the cell cycle and remains high while the cells proliferate. In this report, we show that p36 has the same migration pattern by two-dimensional gel electrophoresis as proliferating cell nuclear antigen (PCNA)/cyclin and that antiserum to PCNA/cyclin selectively immunoprecipitates p36. In addition, by indirect immunofluorescence, PCNA/cyclin accumulates in the nucleus of interleukin 2-stimulated L2 cells during proliferation and is not detectable prior to the initial S phase or after proliferation ceases. These data indicate that PCNA/cyclin expression is induced by interleukin 2 and that PCNA/cyclin accumulation is closely associated with T lymphocyte proliferation.

Autoantigens↗
PubMed1987

Adoptively transferred immunity persists in human marrow graft recipients.

This study was designed to determine if antibodies (Abs) to recall antigens (Ags) were produced after bone marrow transplantation (BMT). Sera from marrow recipients (recipients) were tested for Abs to recall Ags post-grafting, and T and B cells from recipients were tested for their ability to produce anti-tetanus toxoid antibody (anti-TT) using in vitro biosynthesis assays. Neither the donors nor recipients received booster immunizations with recall Ags before or after BMT. Serum Ab titers to tetanus toxoid (TT), diphtheria toxoid (DT), and measles virus (MV) were in the normal range for the majority of 235 short-term recipients (less than 100 days postgrafting) and for the majority of 149 long-term (greater than 6 months postgrafting) recipients. Anti-TT was produced in vitro by peripheral blood lymphocytes (PBL) from 6 of 14 long-term recipients after TT stimulation. In another system, purified B cells from 9 of 21 long-term recipients also produced anti-TT after Epstein-Barr virus (EBV) stimulation. The presence of Ab titers to TT, DT, and MV in the serum of recipients and the production of in vitro anti-TT by T and B cells from recipients show that Ag-specific memory was transferred via the marrow inoculum. These data show that adoptively transferred immunity persists in recipients for years postgrafting.

Antibody-Producing Cells↗
PubMed1985

Amino acid sequence of the alpha subunit of transducin deduced from the cDNA sequence.

Transducin, a GTP-binding protein involved in phototransduction in the vertebrate retina, belongs to a family of homologous coupling proteins that also includes Gs and Gi, the regulatory proteins of adenylate cyclase. Here we report the cDNA sequence and deduced amino acid sequence of transducin's alpha subunit (T alpha). The cDNA was isolated, by screening with an antibody probe, from a bovine retinal cDNA library in the expression vector lambda gt11. The 2.2-kilobase cDNA insert hybridized to a single 2.6-kilobase poly(A)+ RNA species present in extracts of bovine retina but not of bovine heart, liver, or brain. The nucleotide sequence of the cDNA revealed an open reading frame long enough to encode the entire 39-kDa T alpha polypeptide. The polypeptide sequence deduced from the cDNA would be composed of 350 amino acids and have a molecular weight of 39,971. Portions of the sequence matched reported amino acid sequences of T alpha tryptic fragments, including sites specifically ADP-ribosylated by cholera and pertussis toxins. The predicted sequence also includes four segments, ranging from 11 to 19 residues in length, that exhibit significant homology to sequences of GTP-binding proteins, including the ras proteins of man and yeast and the elongation factors of ribosomal protein synthesis in bacteria, EF-G and EF-Tu. In combination with previous functional studies of tryptic fragments of T alpha, the deduced amino acid sequence makes it possible to predict which portions of the polypeptide interact with other molecules involved in retinal phototransduction.

Amino Acid Sequence↗
PubMed1985

Analysis of antigen presentation by metabolically inactive accessory cells and their isolated membranes.

Several amino acid copolymers are potent immunogens under the control of major histocompatibility complex (MHC)-encoded Ir genes. We have further characterized their accessory-cell-dependent, MHC-restricted presentation to T lymphocytes. We initially characterized their processing requirements by investigating the ability of paraformaldehyde-fixed antigen-presenting cells (APC) to present these copolymers. Fixed APC can present poly(Glu56Lys35Phe9) and poly(Glu60Ala30Tyr10) provided that they have been incubated with antigen prior to fixation. The inability of these same fixed preparations to present soluble antigen indicates a fixation-sensitive antigen-processing step. In contrast, the antigens poly(Glu55Lys35Leu10) and poly(Glu55Lys35Tyr10) can be presented by APC fixed before antigen exposure. This differential requirement for antigen processing was exploited to analyze the events of antigen presentation in two related systems. First, the ability of isolated APC membranes to process and present antigen was assessed. APC membranes can present the antigens poly(GluLysLeu) and poly(GluLysTyr) in a specific and MHC-restricted manner. However, the isolated membranes fail to present either poly(GluLysPhe) or poly(GluAlaTyr), suggesting that such preparations can present but not process antigen. Second, the distinct properties of the various copolymers were used with fixed APC to test the effects of antigen processing on the phenomenon of antigen competition. APC that had processed poly(GluLysPhe) or poly(GluAlaTyr) were subsequently fixed and used to present antigen in the presence or absence of various antagonists. Under these conditions, poly(GluLysLeu) and poly(Glu50Tyr50) could effect specific inhibition, clearly indicating that antigen competition occurs distal to and does not require antigen processing. In contrast, native antigen with an absolute processing requirement is not capable of competing with preprocessed antigen on fixed APC. Taken together, these results suggest that processing is important for the molecular interactions between the copolymer antigens and the APC cell surface that are relevant to both antigen presentation and competitive inhibition.

Antigen-Presenting Cells↗
PubMed1978

Combined modality therapy for advanced, diffuse lymphocytic and histiocytic lymphomas.

Forty-six previously untreated patients with advanced aggressive non-Hodgkin's (34 poorly differentiated and mixed diffuse, 8 histiocytic and 4 undifferentiated) were treated with a 3 phase combined modality program employing cyclophosphamide (C), hydroxyl-daunomycin (H), vincristine (O), prednisone (P), procarbazine (P) [CHOP(P)] combination chemotherapy in an initial induction phase, radiotherapy and nonmarrow toxic chemotherapy as a second consolidation phase, followed by a third phase of CHOP(P) chemotherapy for four more cycles. Long-term maintenance therapy was not given. High dose involved field radiation in phase II was limited to volumes encompasing less than 50% of the marrow bearing skeleton. The large majority of patients (82%) had such widespread involvement that this limitation precluded the use of local radiation and were treated instead with a mean of 132 rad of fractionated total body irradiation (TBI). Thirty-eight patients (83%) achieved complete remission. Twenty-nine (66%) of the 44 patients evaluable for follow-up, and 22 (61%) of the 36 patients receiving TBI, remain alive in complete remission for observation periods of up to 26 months.

Adolescent↗
PubMed1978

Chronic cutaneous graft-versus-host disease in man.

This clinicopathologic study of patients with chronic graft-versus-host disease (GVHD) after allogeneic marrow transplantation emphasizes the most prominent feature of the syndrome, the cutaneous aspects, and describes the ophthalmic-oral sicca syndrome with sialoadenitis and the neurologic findings. Chronic cutaneous GVHD affected 19 of 92 recipients surviving 150 days or more. In 6 patients chronic GVHD presented as a continuation of acute GVHD; in 8 it occurred after the resolution of acute GVHD; and in 5 it arose without preceding acute GVHD, ie, de novo late onset. Two cutaneous types were distinguished. The generalized type affected 16 patients and ran a progressive course resulting in late complications of poikiloderma, diffuse dermal and subcutaneous fibrosis, and contractures. Microscopically, it resembled generalized morphea and lupus erythermatosus hypertrophicus et profundus. The local type affected 3 patients with a more variable picture of poikiloderma, dermal sclerosis, and contractures. Microscopically, it resembled lupus of erythematosus profundus and scleroderma. Guidelines for defining and subclassifying chronic cutaneous GVHD are proposed.

Adolescent↗
PubMed1978

Disseminated Nocardia caviae with positive blood cultures.

Disseminated Nocardia caviae infection with multiple positive blood cultures occurred in a bone marrow transplant recipient. Positive blood cultures are unusual in disseminated Nocardia infections and N caviea is an unusual species of Nocardia to cause infections in man, although its virulence in laboratory animals is similar to N asteroides. Multiple positive blood cultures in this case suggest a continuous or recurrent bacteremia rather than a transient bacteremia as previously has been thought to occur in disseminated Nocardia infections. The marked immunosuppressed state of the patient and an indwelling venous line could also have accounted for the recurrent bacteremia.

Adult↗