A taste test for proteases.
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Binding Sites↗
Biomedical subjects
B Dunn
Publications and source records attributed to B Dunn.
Effect of transpulmonary pressure on airway diameter and responsiveness of immature and mature rabbits.
We previously demonstrated that airway responsiveness is greater in immature than in mature rabbits; however, it is not known whether there are maturational differences in the effect of transpulmonary pressure (Ptp) on airway size and airway responsiveness. The relationship between Ptp and airway diameter was assessed in excised lungs insufflated with tantalum powder. Diameters of comparable intraparenchymal airway segments were measured from radiographs obtained at Ptp between 0 and 20 cmH(2)O. At Ptp > 8 cmH(2)O, the diameters were near maximal in both groups. With diameter normalized to its maximal value, changing Ptp between 8 and 0 cmH(2)O resulted in a greater decline of airway caliber in immature than mature airways. The increases in lung resistance (RL) in vivo at Ptp of 8, 5, and 2 cmH(2)O were measured during challenge with intravenous methacholine (MCh: 0.001-0.5 mg/kg). At Ptp of 8 cmH(2)O, both groups had very small responses to MCh and the maximal fold increases in RL did not differ (1.93 +/- 0.29 vs. 2.23 +/- 0.19). At Ptp of 5 and 2 cmH(2)O, the fold increases in RL were greater for immature than mature animals (13.19 +/- 1.81 vs. 3.89 +/- 0.37) and (17.74 +/- 2.15 vs. 4.6 +/- 0.52), respectively. We conclude that immature rabbits have greater airway distensibility and this difference may contribute to greater airway narrowing in immature compared with mature rabbits.
Aging↗
Long-term effects of balloon angioplasty on systemic hypertension in adolescent and adult patients with coarctation of the aorta.
AIMS: To define the long-term effect of balloon angioplasty of aortic coarctation on hypertension, in adolescent and adult patients. METHODS: Balloon angioplasty of discrete, native aortic coarctation was performed on 50 patients (34 male) aged 23+/-8 (mean+/-standard deviation) years. In 42 of these patients cardiac catheterization and angiography were repeated 1 year later, and on the basis of sphygmomanometric blood pressure determination at that time, they were divided into 31 patients (group A) with normalized blood pressure and 11 patients (group B) who still needed antihypertensive medication. Both groups were followed annually thereafter for 12-123 (66+/-37) months. RESULTS: Coarctation gradient values before, immediately after and 1 year after angioplasty were 69+/-24 mmHg, 12+/-8 mmHg (P<0.001) and 7+/-6 mmHg. The corresponding systolic blood pressure values were 165+/-17 mmHg, 128+/-12 mmHg (P<0.001) and 115+/-10 mmHg (P<0.001) in group A; 182+/-21 mmHg, 141+/-24 mmHg (P<0.001) and 134+/-18 mmHg (P<0.001) in group B. Echocardiographic left ventricular mass index before angioplasty and at follow-up was 130+/-31 g x m-2 and 105+/-23 g x m-2 in group A; 157+/-38 g x m-2 and 132+/-35 g x m-2 in group B (P<0.001 for both comparisons). CONCLUSION: Normalization of blood pressure without medication occurred in 74% of patients after angioplasty for aortic coarctation, with subsequent long-term regression of left ventricular hypertrophy. In comparison to reported surgical results, balloon angioplasty should be considered as first line treatment for native, discrete aortic coarctation in adolescent and adult patients.
Adolescent↗
Carboxy terminal variants of Epstein-Barr virus-encoded latent membrane protein 1 during long-term human immunodeficiency virus infection: reliable markers for individual strain identification.
To assess the frequency and molecular polymorphism of malignancy-associated latent membrane protein 1 (LMP1) variants in human immunodeficiency virus type 1 (HIV-1) infection, 94 B-lymphoblastoid cell lines spontaneously derived from peripheral blood mononuclear cells (PBMC) and 30 PBMC samples at seroconversion and later (mean, 55 months) were analyzed by longitudinal comparative sequence analysis in 8 patients progressing to non-Hodgkin's lymphoma (AIDS-NHL), 7 patients to opportunistic infections, and 2 patients with long-term asymptomatic HIV-1 infection. The sequence polymorphism in the C-terminus of LMP1 was characteristic for strains harbored by individual patients, with high fidelity for strain identification. In 14 of the 17 patients, two different but characteristic LMP1 variants were identified. At HIV seroconversion in 8 of 15 patients, a 30-bp deletion (LMP1Delta) was present. Though serial analysis revealed a shift to LMP1Delta in some individuals, statistical analysis of the cohort does not support the hypothesis that accumulation of LMP1Delta variants in PBMC accounts for their observed high incidence in AIDS-NHL.
AIDS-Related Opportunistic Infections↗
Surrogate anatomic/functional sites for evaluating cancer risk: an extension of the field effect.
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Female↗
Short-term exposures of rats to airborne hydrogen fluoride.
A series of acute inhalation exposures was performed with airborne hydrogen fluoride (HF) to establish the concentration response for nonlethal effects in the rat. Exposures were either 2 or 10 min long; concentrations ranged from 135 to 8621 ppm. Three additional exposures (20 to 48 ppm) were performed for 60 min. A mouth-breathing (MB) model with a tracheal cannula was used in most of the exposures to maximize delivery of the HF to the lower respiratory tract. Endpoints on the day after exposure included hematology, serum chemistry, bronchoalveolar lavage, pulmonary function, organ weights, and histopathology. Nasal resistance was measured in nose-breathing (NB) groups. Effects of exposure were generally limited to the respiratory tract and included alveolitis, bronchial lesions, altered parameters of pulmonary function and bronchoalveolar lavage, and mucosal necrosis, inflammation, and fibrinopurulent exudate in airways. Observed changes were concentration related and appeared more pronounced in major airways near the point of entry (trachea in MB animals and nose in NB animals). One group of MB animals exposed for 10 min to 1454 ppm was evaluated at 3 and 14 wk after exposure; the acute effects had resolved by those times. The effects of 2-min exposures were consistently more severe than those from 10-min exposures to the same product of concentration x time. Exposures of MB animals for 60 min to 20 or 48 ppm HF did not result in observable adverse effects, although quasistatic pressure-volume curves were shifted upward slightly after 48 ppm. These data provide an integrated picture of the concentration-related effects of short nonlethal exposures to HF.
Administration, Inhalation↗
Acute effects of 10-minute exposure to hydrogen fluoride in rats and derivation of a short-term exposure limit for humans.
A series of acute inhalation exposures of female rats was conducted with hydrogen fluoride (HF) to establish a concentration-response curve for nonlethal exposures. Durations of 2 and 10 min were used to simulate possible short-term exposures. Concentrations of HF ranged from 593 to 8621 ppm for 2-min exposures and from 135 to 1764 ppm for 10-min exposures. Additional exposures were performed for 60 min at 20 and 48 ppm HF for comparison to existing Emergency Response Planning Guidelines. Animals were evaluated on the day after exposure for changes in parameters of bronchoalveolar lavage, pulmonary function, hematology, serum chemistry, body weight, organ weights, and histopathology. Most exposures were performed with orally cannulated animals to bypass absorption of HF in the nose and achieve maximum delivery of HF to the lower airways. One of the primary uses of the resulting data was to estimate a concentration to which most people could be exposed for 10 min without severe of irreversible health effects. This level was 130 ppm. It was predicted that irritation would occur at this concentration, but the effects on t he respiratory tract would not be "serious" and would be expected to be reversible. The results of this experiment and the subsequent analysis of the data provide an important aid in he planning of responses to an accidental release of HF.
Animals↗
Construction of chimeric enzymes to probe subsite contributions to catalytic specificity.
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Animals↗
Phase I trial of anti-CD3-stimulated CD4+ T cells, infusional interleukin-2, and cyclophosphamide in patients with advanced cancer.
PURPOSE: We performed a phase I trial to determine whether in vivo expansion of activated CD4+ T cells was possible in cancer patients. 111Indium labeling was used to observe trafficking patterns of the infused stimulated CD4+ T cells. The influence of cyclophosphamide (CTX) dosing on immunologic outcome was also examined. PATIENTS AND METHODS: Patients with advanced solid tumors or non-Hodgkin's lymphoma received CTX at 300 or 1,000 mg/m2 intravenously (i.v.). Leukapheresis was performed to harvest peripheral-blood mononuclear cells (PBMCs) either just before the CTX dose, or when the patient was either entering or recovering from the leukocyte nadir induced by CTX. An enriched population of CD4+ T cells was obtained by negative selection. The CD4+ T cells were activated ex vivo with anti-CD3, cultured with interleukin-2 (IL-2) for 4 days, and adoptively transferred. After adoptive transfer, patients received IL-2 (9.0 x 10(6) IU/m2/d) by continuous infusion for 7 days. RESULTS: The absolute number of CD4+, CD4+/DR+, and CD4+/CD45RO+ T cells increased in a statistically significant fashion in all cohorts after the first course of therapy. The degree of CD4 expansion was much greater than CD8 expansion, which resulted in a CD4:CD8 ratio that increased in 26 of 31 patients. The greatest in vivo CD4 expansion occurred when cells were harvested as patients entered the CTX-induced nadir. One complete response (CR), two partial responses (PRs), and eight minor responses were observed. Trafficking of 111Indium-labeled CD4 cells to subcutaneous melanoma deposits was also documented. CONCLUSION: CD4+ T cells can be expanded in vivo in cancer patients, which results in increased CD4:CD8 ratios. The timing of pheresis in relation to CTX administration influences the degree of CD4 expansion. Tumor responses with this regimen were observed in a variety of tumors, including melanoma and non-Hodgkin's lymphoma; a high percentage of patients had at least some tumor regression from the regimen that produced the greatest CD4+ T-cell expansion.
Adult↗
One- to ten-year follow-up results of balloon angioplasty of native coarctation of the aorta in adolescents and adults.
OBJECTIVES: We attempted to evaluate the role of balloon angioplasty in the treatment of discrete coarctation of the aorta in adolescents and adults, with special emphasis on long-term results. BACKGROUND: Controversy persists over the use of balloon dilation for the treatment of native coarctation of the aorta. METHODS: Between July 1986 and January 1997, 43 consecutive adolescent and adult patients with discrete coarctation of the aorta underwent balloon angioplasty. One- to 10-year follow-up data of 37 patients, including results of cardiac catheterization and magnetic resonance imaging (MRI), form the basis of this study. RESULTS: No early or late deaths occurred. Balloon angioplasty produced a reduction in the peak to peak coarctation gradient from a mean +/- SD of 69 +/- 24 mm Hg (95% confidence interval [CI] 61 to 76) to 12 +/- 8 mm Hg (95% CI 10 to 14.8) (p < 0.001). Follow-up catheterization 12 months later (37 patients) revealed a residual gradient of 6.7 +/- 6 mm Hg (95% CI 4.6 to 8.9); 3 (7%) of 43 patients had suboptimal results with development of recoarctation, defined as peak gradient >20 mm Hg, with successful repeat angioplasty. A small aneurysm developed at the site of dilation in 3 (7%) of the 43 patients. MRI follow-up data 1 to 10.8 years (mean 5.2 +/- 2.7) after angioplasty (37 patients) revealed no new aneurysm or appreciable change in the size of the preexisting aneurysm in the three patients. The blood pressure had normalized without medication in 27 (73%) of 37 patients at follow-up examination. CONCLUSIONS: Balloon angioplasty is safe and effective and should be considered a viable alternative to operation for treatment of discrete coarctation of the aorta in adolescents and adults.
Adolescent↗
Genetic and physical maps of Saccharomyces cerevisiae.
Genetic and physical maps for the 16 chromosomes of Saccharomyces cerevisiae are presented. The genetic map is the result of 40 years of genetic analysis. The physical map was produced from the results of an international systematic sequencing effort. The data for the maps are accessible electronically from the Saccharomyces Genome Database (SGD: http://genome-www.stanford. edu/Saccharomyces/).
Chromosome Mapping↗
Contribution of adventitial myofibroblasts to vascular remodeling and lesion formation after experimental angioplasty in pig coronary arteries.
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Angioplasty, Balloon↗
Segregation analysis of ovarian cancer using diathesis to include other cancers.
Despite the recent cloning of BRCA1, BRCA2 and the mismatch repair genes, it will still be a long time before it is possible to specify any individual's risk for ovarian cancer based on her genotype. Most women concerned about their risk on the basis of one or two affected relatives do not belong to extensive ovarian cancer families. Risk calculations depend on a reliable genetic model for ovarian cancer derived, ideally, from the population from which an individual is drawn. We have carried out a segregation analysis using data collected from consecutive ovarian cancer patients in two different centres in the UK. Complex segregation analysis was carried out with the addition of diathesis as a separate parameter allowing other cancers, associated with ovarian cancer, to be taken into account. The use of diathesis in the derivation of this alternative model is described. Analysed under joint likelihood without diathesis, the gene frequency is 0.0028 and penetrance to age 70 years is 50%. This is in agreement with other published models. Incorporating diathesis into the model under joint likelihood gives similar parameters for a single locus model but gives the best fit with a two locus model where both genes are rare.
Adult↗
Angiomatoid malignant fibrous histiocytoma revisited. An immunohistochemical and DNA ploidy analysis.
A histologic, immunohistochemical, and DNA ploidy analyses were performed on two cases of angiomatoid malignant fibrous histiocytoma to ascertain the histogenesis and relationship of endothelial, histiocytic, and fibroblastic elements. Both cases were slowly growing, grossly encapsulated. Subcutaneous masses resected from pediatric patients. Microscopically, the tumors were composed of solid masses of epithelioid and spindle cells with abnormal endothelial-lined and blood-filled cystic spaces surrounded by normal vascular structures and aggregates of lymphocytes occasionally forming germinal follicles. The tumor cells stained exclusively with CD34 and vimentin antibodies. Tumor-associated vessels stained for CD31, CD34, vimentin, and Ulex europaeus. Occasional cells within germinal follicles stained for lysozyme, CD68, and HAM56. Ploidy analysis of tumor cells showed intermediate aneuploidy with a DNA index of 1.14. Blood vessels within and surrounding the tumor as well as inflammatory cells were DNA euploid. These studies suggest that the tumor--though comprised of histologically and immunohistochemically benign-appearing euploid endothelial, fibroblastic, and inflammatory elements--contains an aneuploid population of undifferentiated mesenchymal cells.
Aneuploidy↗
Hospital costs and severity of illness in three types of elective surgery.
BACKGROUND: If patients who are more severely ill have greater hospital costs for surgery, then health-care reimbursements need to be adjusted appropriately so that providers caring for more seriously ill patients are not penalized for incurring higher costs. The authors' goal for this study was to determine if severity of illness, as measured by either the American Society of Anesthesiologists Physical Status (ASA PS) or the comorbidity index developed by Charlson, can predict anesthesia costs, operating room costs, total hospital costs, or length of stay for elective surgery. METHODS: The authors randomly selected 224 inpatients (60% sampling fraction) having either colectomy (n = 30), total knee replacement (n = 100), or laparoscopic cholecystectomy (n = 94) from September 1993 to September 1994. For each surgical procedure, backward-elimination multiple regression was used to build models to predict (1) total hospital costs, (2) operating room costs, (3) anesthesia costs, and (4) length of stay. Explanatory candidate variables included patient age (years), sex, ASA PS, Charlson comorbidity index (which weighs the number and seriousness of coexisting diseases), and type of insurance (Medicare/Medicaid, managed care, or indemnity). These analyses were repeated for the pooled data of all 224 patients. Costs (not patient charges) were obtained from the hospital cost accounting software. RESULTS: Mean total hospital costs were $3,778 (95% confidence interval +/- 299) for laparoscopic cholecystectomy, $13,614 (95% CI +/- 3,019) for colectomy, and $18,788 (95% CI +/- 573) for knee replacement. The correlation (r) between ASA PS and Charlson comorbidity scores equaled 0.34 (P < .001). No consistent relation was found between hospital costs and either of the two severity-of-illness indices. The Charlson comorbidity index (but not the ASA PS) predicted hospital costs only for knee replacement (P = .003). The ASA PS, but not the Charlson index, predicted operating room and anesthesia costs only for colectomy (P < .03). CONCLUSIONS: Severity of illness, as categorized by ASA PS categories 1-3 or by the Charlson comorbidity index, was not a consistent predictor of hospital costs and lengths of stay for three types of elective surgery. Hospital resources for these lower-risk elective procedures may be expended primarily to manage the consequences of the surgical disease, rather than to manage the patient's coexisting diseases.
Aged↗
The Pyloritek test and the CLO test: accuracy and incremental cost analysis.
OBJECTIVE: The aim of this study was to compare the Pyloritek test (a 1-h rapid urease test) to the widely used CLO test. METHODS: Seventy-one patients undergoing upper endoscopy were studied. All patients gave informed consent. A single antral biopsy specimen was obtained for the CLO test, and another was obtained for the Pyloritek test. Additional specimens were obtained for culture and processed in the event of a discordant result. The Pyloritek assay was read at 1 h by one observer. The CLO test was read at 24 h by an observer blinded to the results of the Pyloritek assay. RESULTS: There were 18 males and 53 females, and the mean age (+/- SEM) was 53 +/- 17 yr. Thirty-two patients had a positive result on the CLO test, and 39 had a negative test result. Of the 32 patients with a positive CLO test result at 24 h, 31 were positive by the Pyloritek test at 1 h. All 39 patients with negative CLO test results had negative Pyloritek test results as well. There was one discordant result, a negative Pyloritek test result and a positive CLO test result. Culture demonstrated growth of Helicobacter pylori. The kappa value, a measure of the reliability of the Pyloritek test compared with the CLO test, was 0.972 (SE, 0.0284; 95% confidence interval, 0.925-1). Marginal cost-effectiveness analysis favored the Pyloritek test. CONCLUSIONS: Results of the Pyloritek test at 1 h and the CLO test at 24 h are comparable in terms of detection of urease activity.
Adult↗
Identification of a potential role for the adventitia in vascular lesion formation after balloon overstretch injury of porcine coronary arteries.
BACKGROUND: In the present series of experiments, we examined the onset of cell proliferation and growth factor expression after balloon overstretch injury to porcine coronary arteries. METHODS AND RESULTS: Domestic juvenile swine underwent balloon overstretch injury to the left anterior descending and circumflex coronary arteries with standard percutaneous transluminal coronary angioplasty balloon catheters. To identify proliferating cells, 5-bromo-2-deoxyuridine (BrDU) was administered over a period of 24 hours before the animals were killed at either 1, 3, 7, or 14 days after injury. Immunohistochemistry was performed with monoclonal antibodies to BrDU and smooth muscle cell markers. Three days after injury, a large number of proliferating cells were located in the adventitia, with significantly fewer positive cells found in the media and lumen. Seven days after injury, proliferating cells were found primarily in the neointima, extending along the luminal surface. In situ hybridization for PDGF A-chain and beta-receptor mRNAs revealed that the expression of these two genes was closely correlated with the sites of proliferation at each time point. Studies in which BrDU was injected between days 2 and 3 and the animals were killed on day 14 suggested that the proliferating adventitial cells may migrate into the neointima. CONCLUSIONS: These data suggest that adventitial myofibroblasts contribute to the process of vascular lesion formation by proliferating, synthesizing growth factors, and possibly migrating into the neointima. Increased synthesis of alpha-smooth muscle actin observed in the adventitial cells after arterial injury may constrict the injured vessel and contribute to the process of arterial remodeling and late lumen loss after angioplasty.
Animals↗