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K Sullivan

Publications and source records attributed to K Sullivan.

At least 145 records · Page 8Linked to original sources
PubMed1987

Intracellular autoantigens: diagnostic fingerprints but aetiological dilemmas.

Autoimmune diseases such as systemic lupus erythematosus, scleroderma, Sjögren's syndrome, mixed connective tissue disease and dermato/polymyositis are each characterized by distinct sets of autoantigens and antibodies which confer on each disease a specific immune profile or fingerprint. These immune fingerprints have advanced our management of this group of diseases, as aids in differential diagnosis and earlier recognition. In lupus and scleroderma, multiple antigen/antibody systems characterize these fingerprints and the autoantigens appear to be located in separate cell compartments of the nucleus, nucleolus and cytoplasm. Because these antibodies are so distinctive for each disease, the response must be antigen driven or at least antigen directed. However, the apparent multi-focus location of the autoantigens poses a problem. It now appears that in scleroderma this dilemma may be explained by the consideration that at a certain time point in cell metabolism all the known autoantigens may be assembled at one location to form a single structural entity. It is possible that this assembly of antigens may be required for a specific cellular function. An autoimmune response to this transiently assembled structure comprising several different proteins and nucleic acids could result in the complex immune response seen in this disease.

Antigen-Antibody Reactions↗
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↗
PubMed1987

The treatment of acute non-lymphoblastic leukemia by allogeneic marrow transplantation.

The results are presented of allogeneic transplantation for 363 patients with acute non-lymphoblastic leukemia treated in Seattle from May 1973 through December 1985. The probabilities of surviving disease-free for 5 years for patients transplanted in first remission, in second remission, in untreated first relapse or in chemotherapy-resistant first relapse were 46%, 28%, 30%, and 21%, respectively. The corresponding probabilities of relapse within 5 years were 25%, 37%, 36% and 56%, respectively. Prognostic factors predictive of survival after marrow transplantation for patients transplanted in first remission included age, donor sex and the number of circulating blasts at the time of diagnosis. Acute graft-versus-host disease (GVHD) had a major adverse effect on survival, but chronic GVHD decreased the risk of relapse for patients transplanted in first remission.

Bone Marrow Transplantation↗
PubMed1987

Marrow transplantation for patients with acute lymphoblastic leukemia in first marrow remission.

Forty-six patients with acute lymphoblastic leukemia (ALL) in first marrow remission underwent allogeneic marrow transplantation between August 1976 and June 1985. Thirty-four patients had no extramedullary disease after remission induction and 12 had extramedullary relapses prior to or at the time of marrow grafting. The conditioning regimen included cyclophosphamide followed by total body irradiation, 9.2-15.75 Gy, administered as a single dose or in six or seven daily fractions. Marrow donors were genotypically HLA-identical siblings. Methotrexate was given as prophylaxis for graft-versus-host disease (GVHD). Forty-four patients had marrow engraftment. The incidence of grades II-IV acute GVHD was 52%. Clinical chronic GVHD occurred in 21 patients. Eighteen patients are alive 1-9 years (median = 4.2 years) after marrow grafting, 15 of whom are in continuous complete remission. The estimated probability of relapse within 2 years (+/- standard error) is 41 +/- 9% and the probability of relapse-free survival at 5 years is 28 +/- 7%. Major causes of death were recurrent leukemia, acute GVHD and interstitial pneumonia. Actuarial probabilities of survival, relapse and disease-free survival were not significantly different between those patients who did and those who did not have extramedullary disease after attaining first marrow remission.

Bone Marrow Transplantation↗
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↗
PubMed1985

Clinical mumps vaccine efficacy.

From February 5 through April 23, 1982, 110 cases of mumps were reported among 357 students in a middle school in Ashtabula County, Ohio, an overall attack rate of 31%. Vaccine efficacy was calculated using a variety of case definitions, case surveillance systems, and vaccination-status ascertainment methods to evaluate their effects on the estimated vaccine efficacy. From data collected at the school for case ascertainment and vaccination status, clinical vaccine efficacy was initially estimated at 37%. By means of a uniform case definition (parotitis lasting two days or more) and only cases and vaccination status ascertained from parental questionnaires, estimated vaccine efficacy increased to 70%. From secondary attack rates in household members with provider-verified vaccination status, the vaccine efficacy further increased to 85%. This outbreak investigation confirms that the methods used to ascertain cases and determine vaccination status greatly affect estimates of vaccine efficacy. Studies relying solely on school records for case finding and determination of immunization status may provide misleadingly low estimates of vaccine efficacy for mumps vaccine as well as for other vaccines. Appropriate methods demonstrate that mumps vaccine is highly effective and support recommendations for its continued use.

Adolescent↗
PubMed1985

Graft versus host disease-related secretory immunoglobulin A deficiency in bone marrow transplant recipients. Findings in labial saliva.

Graft versus host disease-dependent decreases in salivary IgA levels were sought in labial gland saliva samples from bone marrow transplant recipients. Transplantation-associated, irradiation-related effects were also present, but these could be avoided if analyses were performed at 1 year or later after transplantation. Sampling of minor gland saliva eliminated the possibility of contamination with IgA-rich serum transudates arising from gingival or mucosal pathways which obscured results from previous studies using whole saliva samples. Patients with active extensive clinical disease had significantly depressed levels of salivary IgA. Since labial saliva is a principal source of total salivary IgA, the present findings may explain why patients with graft versus host disease are susceptible to infection via the sinobronchial portal.

Adult↗
PubMed1984

Partial cDNA sequence of the gamma subunit of transducin.

A 151 bp cDNA segment that encodes the amino-terminal portion of the gamma subunit of bovine transducin was isolated from a retinal cDNA library constructed in the expression vector lambda gt11. The base sequence of this cDNA confirms the sequence of the first 39 amino-terminal amino acids reported for the native protein (McConnell et al. (1984) Fed. Proc. 43, 1585). Northern blot analysis indicates that the complete mRNA is approximately 650 bases long and that its expression is limited to the retina.

Amino Acid Sequence↗
PubMed1984

Demonstration of a polarizing signal that reverses future retinotectal patterns across Nuclepore filter barriers, in Xenopus embryonic eye.

We have studied the interactions which occur in surgically disarranged eye rudiments by recombining a left anterior half-eye graft from a donor Xenopus embryo with a right host posterior half eye, across a variety of physical barriers, at embryonic stages 31 or 32. The anterior half-eye graft and barrier were removed 18 h later at stage 38, and the host posterior half-eye was allowed to reconstitute a whole eye whose visuotectal projection could be mapped electrophysiologically after metamorphosis. Anteroposteriorly reversed maps and double-anterior twinned maps that are characteristic of anterior half-eyes, were found in 50-65% of cases in each of the experimental series using no barrier (N = 16), or using Nuclepore filter barriers (N = 47), including 5 of 8 cases when a filter of 0.015 micrometer pore diameter was used. The latter cases are especially interesting, because the filter pores were much smaller than the minimum size known to permit cell-cell contact through the pores. No animals showed AP-reversed retinotectal maps or double-anterior twinned maps when the graft and host half-eyes were separated by a tantalum or plastic barrier (N = 21). Only a single case of AP-reversed mapping was found in 115 control animals including simple posterior half-eye preparations at stage 32 or 38 (N = 13), sham fusions (30 min) across Nuclepore filters (N = 35), or chronic application of a filter (or plastic or tantalum) barrier from stages 32-38 (N = 55) without a left anterior half-eye graft. We conclude that signals from an anterior half-eye can act to repolarize a posterior half-eye in the absence of cell transfer and under conditions which permit little or no direct cell-cell contact.

Animals↗
PubMed1984

Murine monoclonal anti-T cell antibodies for treatment of steroid-resistant acute graft-versus-host disease.

Four different murine monoclonal anti-T cell antibodies were administered to 15 patients with severe steroid resistant graft versus host disease (GVHD) in a phase I clinical trial in order to evaluate feasibility and toxicity. Antibodies 9.6 (IgG2a) and 35.1 (IgG2a) bind to separate epitopes on the E receptor (Tp50); antibody 10.2 (IgG2a) binds to the murine Lyt-1 homolog (Tp67); and antibody 12.1 (IgG2a) binds to a cell surface antigen with a molecular weight of approximately 100,000 daltons (Tp100). A total of 151 infusions were given, ranging in dose from one to 20 mg, each administered over a one to four hour period. One patient received a total of 259 mg of antibody over a period of 45 days. Six infusions (4%) in two patients were associated with fever or fever and chills. By decreasing the infusion rate, subsequent infusions to these two patients were accomplished without additional reactions. Although most of the patients treated with monoclonal antibodies required platelet support, the number of platelet units given was not significantly different from similar patients not receiving monoclonal antibodies. Six of ten patients receiving intermediate to high doses (5-20 mg) antibody therapy had evidence of at least partial improvement in GVHD in at least one involved organ system. None of the patients became immunized to mouse immunoglobulin. Our results suggest that therapy of GVHD with murine monoclonal anti-T cell antibodies is feasible and that these antibodies apparently can be administered to marrow transplant patients without significant toxicity. Further studies are required to determine which antibodies or combinations of antibodies have optimal anti-GVHD effect.

Acute Disease↗
PubMed1983

Mixed lymphocyte reactions for individuals with phenotypic identity for specific HLA-B,DR determinants: the role of linkage disequilibrium and of specific DR and other class II determinants.

Although many patients who might benefit from therapeutic bone marrow transplantation lack HLA identical sibling donors, results from many centers now indicate that transplants involving donors other than identical siblings have been successful in a substantial number of cases. Most of these cases were selected because cells from the patient and donor were compatible in mixed lymphocyte culture. We have previously shown that the prediction of mixed lymphocyte culture nonreactivity by HLA-B,DR matching is far more successful if the matched donors shared antigen combinations known to possess significant positive linkage disequilibrium. We now also show that cells from donors with unrelated haplotypes having the specific DR determinants DR1, DR2, and DR3 are more likely than cells from donors with other haplotypes to be mutually compatible in mixed lymphocyte culture. However, even cells from donors with haplotypes with the highest levels of positive linkage disequilibrium frequently show significant mutual stimulation which can, in selected family studies, be attributed to determinants like SB that map between HLA-D/DR and GLO.

Bone Marrow Transplantation↗
PubMed1982

Depolymerization of dendritic microtubules following incubation of cortical slices.

Electron microscopical examination indicated that incubation of slices of rat cerebral cortex in Krebs buffer at room temperature of 37 degrees C led to a rapid and more or less complete depolymerization of dendritic microtubules. The loss of dendritic microtubules did not appear to be a consequence of anoxia. Myelinated axons showed only a partial loss of microtubules and the microtubules of preterminal axons were unaffected by incubation. These results indicate differential labilities of axonal and dendritic microtubules under these conditions of incubation. Such an effect of the incubation of slices in Krebs buffer indicates a need for caution in the interpretation of experiments on slice preparations.

Animals↗