Organ donation: new ways needed to keep up with the demand. Part II.
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Biomedical subjects
Publications and source records attributed to R Evans.
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In previous reports, we have shown that adoptive transfer of tumor-sensitized T (immune) cells to tumor-bearing mice that have received a prior injection of cyclophosphamide (CY) results in the induction of permanent tumor regression in syngeneic strains. It has also been shown that adoptive immunotherapy results in an increased expression of class II MHC antigens (Ia) by macrophages at the tumor site and in the peritoneal cavity and is associated with expansion of CD4+ and CD8+ T cells at the site of tumor regression. In this report, we use the Ia mutant strain, B6.C-H-2bm12, and congenic C57BL/6J (B6) mice to determine the relative importance of Ia expression in regulating amplification of immune responses following adoptive immunotherapy and to test the hypothesis that recognition of congenic Ia determinants will result in the induction of suppressor mechanisms that down-regulate active immunity. The data indicated that the adoptive transfer of immune congenic T cells (B6 immune cells into CY-treated tumor-bearing bm12 mice and vice-versa) down-regulated active immunity, while the transfer of syngeneic immune cells resulted in permanent tumor regression. By using radiation-chimeric mice, it was shown that down-regulation was associated with incompatibility of the transferred immune T cells and bone-marrow-derived cells (putatively expressing the Ia haplotype of donor-derived macrophages) and the appearance of long-lived splenic suppressor cells. Suppression per se was shown to be induced in response to the Ia difference between the two strains and not in response to the MCA/76-9 sarcoma, which appears to be one of the few tumors that can induce active immunity in both the syngeneic and congenic strains without obvious subsequent down-regulation by suppression.
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In a 12-month period, 177 patients at risk of infection with human immunodeficiency virus (HIV) or hepatitis B were operated on. Sixty-nine had HIV antibodies. The procedures used to identify these patients and minimize the risk of infection of hospital staff in the operating department are described. All staff working in the operating department were surveyed to determine their caseload, feelings of anxiety, and the incidence of high-risk exposure to infection. Anxiety was not related to workload, but was more common in those who had high-risk exposure. All members of staff who sustained a needlestick injury were tested for HIV antibodies at intervals after injury; 33 also volunteered to be tested in a screening session 3 months after the study period. None had HIV antibodies, suggesting that the risk of acquiring HIV infection in the operating department is low.
Previous data indicated that progressive growth of the C57BL/6J sarcoma, MCA/76-9, was associated with a systemic increase in the level of IL-1 activity in peritoneal and tumor-associated macrophages. In this paper, the hypothesis was tested that macrophage IL-1 alpha and beta gene expression was regulated by the specific macrophage growth factor, CSF-1, produced by tumor cells. The data indicated that all of the nine C57BL/6J, BALB/cJ, and C3H/HeJ sarcomas tested transcribed the CSF-1 gene. The tumor cell culture supernates induced proliferation of bone marrow cells that differentiated into macrophages. Moreover, proliferative activity of conditioned medium and the ability to induce macrophage differentiation were abrograted by neutralization with the 5A1, rat-anti-mouse monoclonal anti-CSF-1 antibody. Conditioned medium from tumor cell cultures, as well as recombinant CSF-1 and L cell-conditioned medium, induced transcription of the IL-1 alpha and beta genes, the latter being more strongly expressed. IL-1 gene transcription was not induced after neutralization of the culture supernates by the monoclonal antibody, 5A1. The overall data would support the hypothesis that the pathway in vivo leading to the increased IL-1 expression by macrophages is regulated by at least one tumor cell product, CSF-1.
It has been previously reported that tumor-associated macrophages isolated after combination therapy contained an activity that inhibited thymocyte proliferation in the IL-1 comitogenic assay. The present report shows that this macrophage-derived inhibitory factor (MDIF) inhibits DNA synthesis in diverse adherent and nonadherent cells in vitro. The elution pattern seen after chromatography using Bio-Gel P10 or Sephadex G-25 columns indicated a molecular size of 3-6.5 kDa. However, full activity was retained when MDIF was passed through an Amicon filtration membrane having a cut off of 500 Da. It was also seen that other molecules less than 500 Da, such as thymidine, thimerosal, and PGE2, each of which was also shown to be growth inhibitory, eluted in a size range similar to that of MDIF after chromatographic separation. Ion exchange chromatography confirmed that MDIF was distinct from thymidine, and a radioimmunoassay indicated that PGE2 was not responsible for MDIF activity. Little or no inhibitory activity could be detected in macrophages isolated from progressing tumors or from tumors excised after cyclophosphamide treatment of tumor bearers. Given that this inhibitory activity was associated with macrophages derived from tumors induced to regress by combination therapy, the possibility is discussed that MDIF may play an important role during the regulation of immune reactions at the tumor site.
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To define airborne allergen exposure during various tasks with rats in a laboratory, concentrations of allergen Rat n I were measured by radioimmunoassay in extracts from filters in personal air sampling devices that were worn by laboratory workers while they were performing these tasks. The tasks included feeding, cage cleaning, handling, injection, surgery, and sacrifice. Median concentrations encountered during feeding or cleaning (21 ng/m3) and injection or handling (13 ng/m3) were higher than those associated with surgery or sacrifice (3.1 ng/m3; p less than 0.01). Area samples in animal-holding rooms contained 3.4 ng/m3 during animal handling and 2.3 ng/m3 at other times. Very low concentrations were found in air outside the handling room, in unused laboratories, or outside air. We concluded that certain tasks incur a higher risk of allergen exposure but that exposure may occur anywhere within an animal laboratory environment.
Immune responses to formaldehyde (F) have been recorded for seven decades. More recently, sensitive assays for antibody against F-human serum albumin (HSA) have been reported. IgG antibody against F-HSA has been said to correlate with symptoms against F-HSA. We report on 61 serum samples analyzed for IgG antibodies against F-HSA. IgG antibodies against F-HSA were most prevalent in subjects who had received intravenous F. In no case (either presumed symptomatic to F or with IgG antibody against F-HSA) was there a correlation of serologic results with symptoms. We also reviewed inhalation disease caused by chemicals and proteins acting as immunogens and report that at this time there is no evidence that gaseous F meets the criteria for causation of inhalational IgG-mediated lung disease by clinical or serologic studies. Very high IgG antibody levels occur in respiratory immunologic inhalational disease, and the absence of these high IgG levels against F is strong evidence against F or F proteins being an inhalational antigen of significance.
A method has been devised using an electronic spread sheet that will shorten the data processing time and give a printed report of the results. Lithium Fluoride chips are used in pairs so as to produce the same average response. The raw TL readings along with descriptive comments are entered into the computer. The program then computes the single chip dose, the average dose for each chip pair, applies a non-linearity correction factor and prints out a report with comments and patient data. The program offers several advantages: It is much faster than hand calculations, it provides a precise and accurate conversion of raw data to final data, and outputs an organized display of calibration factors, input data, dosimetry data, patient data and listing of involved personnel. The program is easy to use and can be run on any computer that can support a spreadsheet program.
This paper has reviewed research and other papers that have furthered our understanding of the impact of the presence of a child with sickle cell disease on the family. The research suggests that the primary parent in such a family experiences additional emotional strain much like primary parents of children with other chronic illnesses have been found to exhibit. The research also suggests that the ill child's presence influences interpersonal relationships within the family. Specifically, there is some evidence that the relationship between the parents and the relationship between the parent and other offspring may be affected adversely. The only evidence for an adverse impact on the relationship between the parent and the chronically ill child was in our research when considering only single-parent families. The research also suggests that the family environment is affected. In particular, the research suggests that the level of conflict and organization within the family was less favorable than within the control families. Moreover, the research suggests that the child's presence reduces the ability of the primary parent to participate in social activities outside of the family. Secondary parents, on the other hand, report less satisfaction with the extent to which their own individual needs are being met within the family. The available research also suggests that other factors mediate the impact of the child's illness on the family. In particular, parents with more knowledge about the illness and more social support available appear to cope more favorably with the illness. Moreover, the available research also suggests that the family also impacts on how the patient responds to the illness. Specifically, the more psychosocial stressors within the family, the less effectively the patient copes with the illness. In addition, the more social support available to the patient from the family and other significant others, the more likely the patient is to comply with the treatment regimen. Finally, two methodological issues have been discussed. First, a tendency is evident for parents to deny any impact on the family when asked directly but to demonstrate the impact when the responses of these parents are compared to the responses of a comparison group. This suggests a need for more studies that involve a comparison group in the design. Second, the small sample sizes in many of the studies reflect the lack of adequate sample in individual geographic locales. This suggests a need for more collaborative research projects such as the CSSCD project to increase sample size.
The aim of this study was to try to gather orthodontists' current opinions regarding the prevention of cross-infection, to correlate this and suggest some guidelines acceptable to the profession.
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