Biomedical subjects
Publications and source records attributed to K Sullivan.
A new automated affinity-chromatographic method for the rapid determination of glycated hemoglobin is described. It has a four min cycle time, does not measure the labile fraction of glycosylated hemoglobin and is not interfered with by abnormal hemoglobins.
The flash lamp excitation of coumarin dye to produce light energy of the specific wavelength of 504 nm is the basis for the new wave of pulsed dye lasers. Numerous urological applications have been developed. Treatment of ureteral and renal calculi has proven to be an atraumatic and effective treatment modality. Most recently, this technology has been applied to the endoscopic treatment of biliary calculi. The authors review the most recent treatment techniques in both biliary and urinary stone disease.
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We prospectively evaluated 169 patients with a number of screening studies performed between 71 to 121 days after allogeneic marrow transplantation to detect the development of chronic graft-versus-host disease (GVHD). Group 1 patients (n = 78) were asymptomatic and had normal physical examinations at the time of screening and, with a minimum of 8 years follow-up, have not developed chronic GVHD. Group 2 patients (n = 38) had signs and symptoms of chronic GVHD at time of testing. Group 3 patients (n = 53) were similar to those in group 1 in having no clinically evident GVHD at the time of testing, but later developed clinical chronic GVHD. Using time to an event analysis, we compared patients in groups 1 and 3 to determine which of 17 clinical and laboratory factors evaluated at screening accurately predicted the development of subsequent chronic GVHD. Multivariate analyses showed several factors to have independent predictive value. In the first model, results of oral biopsies were excluded since these were done only in one half of the patients. Predictive factors in this analysis included: (1) histologic findings of GVHD on skin biopsy, relative risk 3.23 (95% confidence interval 1.75 to 5.94), P = .0002; and (2) history of grade II through IV acute GVHD, relative risk 3.12 (95% confidence interval 1.72 to 5.64), P = .0002. When oral biopsy results were included in the second model, independent risk factors included: (1) histologic findings of GVHD on skin biopsy, relative risk 5.96 (95% confidence interval 1.95 to 18.19), P = .0017; and (2) low numbers of immunoglobulin A (IgA)-bearing plasma cells detected by direct immunofluorescence in salivary gland areas on oral biopsy, relative risk 11.53 (95% confidence interval 2.51 to 52.03), P = .0017. Our study demonstrates the value of day 100 screening studies for predicting subsequent development of clinical chronic GVHD.
A computerised system has been used to store DNA profiles from 3 hypervariable loci. This initial survey illustrates that band matching is only possible after analysis of the errors associated with electrophoretic systems. A number of databases have been constructed with the three probes investigated and two methods of frequency determination, 'binning' and 'sliding window' fitting, have been compared.
Malnourished children may also have siblings at increased risk of poor health. Early identification of siblings at risk could lead to timely intervention to prevent the development of malnutrition or other potentially life-threatening events. In a nationwide survey conducted in Peru in 1984, stunting in an older sibling (defined as height/age less than or equal to 3.00 SD of the NCHS/CDC reference median) was evaluated as an indicator for stunting in a target sibling (next youngest) sibling) (n = 3284). The prevalence of stunting was much higher in target siblings who had an older sibling with stunting compared to those whose older sibling was not stunted, with prevalence ratios of 8.5 in Lima, 4.7 in urban areas, and 2.5 in rural areas. Screening indices (sensitivity, specificity, and predictive value positive) also showed marked variation across regions. The variation in this indicator's performance across regions demonstrates the importance of evaluating screening tools within the populations where they will be applied. Regional variations in the performance of malnutrition indicators should be anticipated because malnutrition is the result of a complex, multifactorial process.
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A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.
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The cumulative incidence of chronic graft-versus-host disease (GVHD) was 48% among 165 patients with severe aplastic anemia who had been discharged from Seattle 3 months after they were treated with marrow grafts from HLA-identical siblings. Estimated 10-year survival was 85%. Preceding acute GVHD had a dominating influence on the development of chronic GVHD. Almost all patients with grades II-IV and 67% of those with grade I acute GVHD developed chronic GVHD. Among patients without previous acute GVHD, three factors were independently correlated with an increased risk of de novo chronic GVHD: increasing patient age, the infusion of buffy coat cells in addition to the marrow, and corticosteroid therapy before transplantation. For example, patients below and above age 20 years who had neither buffy coat cell transfusions nor preceding corticosteroid therapy had an incidence of chronic GVHD of only 4-8%, while those with either buffy coat cell transfusions or corticosteroids or both had incidence rates of 33-70%. The development of chronic GVHD significantly influenced survival. Among 83 patients without chronic GVHD, only one died (on day 150 with interstitial pneumonia), compared to 23 deaths among 82 patients with chronic GVHD. For results of marrow grafting for aplastic anemia to improve, better prevention of chronic GVHD is needed.
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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.
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.
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Twenty-nine patients were conditioned for allogeneic marrow transplant with cytarabine (ara-C) (3 g/m2 every 12 hours for 12 doses) and total body irradiation (TBI) (200 cGy daily for six days) with or without cyclophosphamide (CY) (60 mg/kg) to determine toxicity and efficacy. Four patients had chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, and 25 patients had acute leukemia, 24 at stages later than first remission. Three patients (10%) had fatal regimen-related toxicity and another 10% experienced severe toxicity in at least one organ system. The addition of CY to the ara-C and TBI regimen was not associated with an increase in the frequency of severe toxicity. Twenty-five of 29 patients engrafted eight to 33 days posttransplant: three died early before engraftment, and one patient failed to engraft. Ten of 29 patients are alive without disease, and the actuarial probability of disease-free survival for the entire group at 3 years is 33%. Three of ten patients with acute nonlymphocytic leukemia (ANL), six of 15 with acute lymphocytic leukemia (ALL), and one of four with CML are alive and disease free 25 to 42 months (median, 30 months) after transplant. High-dose ara-C (HDara-C) and TBI with or without CY can be administered with approximately the same toxicity as CY plus TBI. Phase III studies appear warranted to determine if these newer regimens provide improved results compared with currently used regimens.
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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.
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.