Human small cell lung carcinoma (SCLC) cells have been shown to contain significant levels of a bombesin-immunoreactive peptide. The 27-amino acid peptide, gastrin releasing peptide (GRP), has recently been shown to be responsible for the bombesin-like immunoreactivity found in SCLC cells. Among four lung cancer cell lines examined in vitro, GRP exhibited mitogenic activity for two SCLC subtypes, but not for a squamous carcinoma or adenocarcinoma lung cell line.
Background-Immunoregulatory abnormalities of T cells might be of importance in the pathogenesis of pouchitis after ileoanal pouch anastomosis (IAP).Aims-To characterise T cell subsets, their state of activation, and production of cytokines in inflamed and non-inflamed pouches in patients with ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The influence of T cell activation on mucosal transformation was also studied. Patients-Mucosal biopsy specimens were taken from 42 patients with IAP (33 with UC and nine with FAP).Methods-Mononuclear cells were isolated by standard techniques and characterised by three colour flow cytometry. Interferon (IFN-) production was studied using the ELISPOT technique.Results-In patients with UC with pouchitis there was a significant increase in the CD4:CD8 ratio, expression of activation markers on CD3+ cells, and number of IFN producing mononuclear cells compared with patients with UC without pouchitis (CD4:CD8 ratio 1.3 (range 0.7-2.7) versus 0.6 (0.1-1.0), p=0.012). In addition, a positive correlation between increased crypt depth and the number of CD4+ cells (r=0.57) was shown. Conclusion-The observed increase in activated mucosal CD4+ T cells and IFNproduction might lead to mucosal destruction and crypt hyperplasia as seen in pouchitis. (Gut 1998;43:499-505)
Hematotoxicity is a life-threatening side effect of many chemotherapy regimens. While clinical factors influence patient responses, genetic factors may also play an important role. We sought to identify genomic loci that influence chemotherapy-induced hematotoxicity by dosing Diversity Outbred mice with one of three chemotherapy drugs; doxorubicin, cyclophosphamide or docetaxel. We observed that each drug had a distinct effect on both the changes in blood cell sub-populations and the underlying genetic architecture of hematotoxicity. For doxorubicin, we mapped the change in cell counts before and after dosing and found that alleles of ATP-binding cassette B1B (Abcb1b) on chromosome 5 influence all cell populations. For cyclophosphamide and docetaxel, we found that each cell population was influenced by distinct loci, none of which overlapped between drugs. These results suggest that susceptibility to chemotherapy-induced hematotoxicity is influenced by different genes for different chemotherapy drugs.
A clinicoepidemiologic study was undertaken to investigate an apparent increase in frequency of nosocomial invasive filamentous fungal disease (NIFFD) in adult patients with acute leukemia hospitalized during a period of hospital construction, and to determine if a relationship existed between the construction activity and the acquisition of NIFFD. The first study goal, to determine the incidence of NIFFD before and during construction, was approached by calculation of incidence rates of NIFFD in patients with acute leukemia, comparing 1982 and 1983 (a baseline period free of construction) to 1986 (a year when construction activity was at its peak). The second study goal, to identify risk factors for the development of NIFFD, was accomplished by reviewing the autopsy records of all patients with underlying hematologic disorders accompanied by granulocytopenia who died in our hospital from 1982 through 1986. Patients with and without autopsy evidence of NIFFD were then compared by univariate and multivariate (logistic regression) analysis to identify potential risk factors for the acquisition of NIFFD. The incidence of NIFFD in patients with acute leukemia hospitalized during the period of hospital construction was significantly increased when compared to a baseline period without construction (11 per 139 versus 4 per 333, p less than .001). Review of all granulocytopenic patients autopsied over the five-year interval 1982 through 1986 revealed duration of granulocytopenia and hospitalization during construction to be risk factors for NIFFD by univariate analysis (p less than .005). Logistic regression showed duration of granulocytopenia to be highly significant independent risk factor (p less than .01) and construction activity to be a probable independent risk factor (p = .09).(ABSTRACT TRUNCATED AT 250 WORDS)
Decisions on adopting new manufacturing technologies are often biased because they are based only on those impacts that can be expressed in financial terms. Multi-criteria decision tools that include nonfinancial impacts avoid this bias. One such tool, the analytic hierarchy process (AHP), has been modified for the manufacturing environment and incorporated into AutoMan, decision support software for microcomputers. The modified AHP is used here to decide on the best way to automate a machine shop. The four steps are: (1) specify criteria and alternatives; (2) weight criteria using pairwise comparison judgments; (3) rate alternatives with respect to criteria; and (4) compute the overall weighted score for each alternative. This approach preserves existing reliable financial information and integrates it with both nonfinancial quantitative performance data and qualitative informed judgments. Judgments are made explicit and checked for consistency. Over 800 industrial managers have purchased AutoMan to improve their automation decisions.
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