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Biomedical subjects

D Snider

Publications and source records attributed to D Snider.

11 recordsLinked to original sources
PubMed2001

Early intestinal Th1 inflammation and mucosal T cell recruitment during acute graft-versus-host reaction.

Little is understood about the earliest cytokine responses and the role(s) of donor CD4 T cells in the intestine during the induced graft-vs-host reaction (GVHR). We investigated the activation and mucosal homing phenotype of the donor CD4 cells and the kinetics of cytokine responses within the intestine and associated lymphoid tissues during early GVHR. Significant frequencies of donor CD4 cells accumulated within recipient Peyer's patches (PP), mesenteric lymph nodes (MLN), lamina propria (LP), and spleen (SP), during the first 9 days of GVHR. Many donor CD4 cells in SP, MLN, and LP expressed CD44 and also expressed de novo the mucosal homing integrin alpha(4)beta(7) (LPAM-1). A large IFN-gamma response occurred by day 3 in cells from PP and MLN, but much later (day 9) in SP and LP cells. IL-10 production by SP and MLN cells was elevated initially but declined substantially by day 9. IL-4 production by SP, MLN, and PP cells was low on day 3 and showed gradual decline in LP by day 9. IL-5 production by LP cells gradually increased in direct contrast to IL-5 production by MLN cells. The MLN CD4 cells showed the most dynamic changes, with high numbers of activated/effector donor CD4 cells and altered cytokine production consistent with a developing Th1 response. The IFN-gamma responses in PP and MLN preceded that of the SP, suggesting an intestinal origin for some Th1 effector cells in GVHR. Donor CD4 T cells apparently acquire the ability to home to the LP during early GVHR.

Acute Disease↗
PubMed1999

Graveside care.

Explore the source record for details and available documents.

Accidental Falls↗
PubMed1998

Disruption of antigen-induced inflammatory responses in CD40 ligand knockout mice.

The objective of this study was to investigate the contribution of the interaction between CD40 and its ligand (CD40L) to antigen-induced airways inflammatory responses. To this end, we used a model involving ovalbumin (OVA) sensitization followed by OVA aerosol challenge in CD40L knockout (KO) mice. OVA-specific IgE and IgG1 were detected in the serum of the sensitized control, but not in CD40L-KO mice. After antigen challenge, sensitized control mice developed airway inflammation that was primarily eosinophilic. This inflammatory response was dramatically reduced in CD40L-KO mice. In contrast, similar numbers of eosinophils were observed in both the bone marrow and the peripheral blood in the sensitized controls and mutant strains after antigen challenge. To investigate the mechanisms underlying these findings, we examined levels of the cytokines IL-5, IL-4, and TNFalpha in both bronchoalveolar lavage (BAL) and serum. Similar levels of IL-5 were detected in BAL and serum of control and CD40L-KO mice; however, negligible levels of IL-4 in BAL and serum and of TNFalpha in BAL were detected in CD40L-KO mice when compared with control mice. Furthermore, we demonstrated that endothelial cell expression of vascular cell adhesion molecule 1 in OVA-sensitized and -challenged CD40L-KO mice was, as detected by immunohistochemistry, markedly decreased compared with that observed in similarly treated control mice. In addition, we locally overexpressed IL-4 and TNFalpha by using an adenoviral (Ad)-mediated gene transfer approach. Intranasal administration of either Ad/TNFalpha or Ad/IL-4 into OVA-sensitized and -challenged CD40L-KO mice did not reconstitute airway eosinophilia. However, concurrent administration of Ad/TNFalpha and Ad/IL-4 upregulated endothelial expression of vascular cell adhesion molecule 1, and resulted in full reconstitution of the inflammatory response in the airways. Together, these findings demonstrate the importance of the CD40-CD40L costimulatory pathway in the full expression of the inflammatory response in the airways.

Adenoviridae↗
PubMed1997

Tumour immunotherapy using an adenoviral vector expressing a membrane-bound mutant of murine TNF alpha.

The most limiting factor regarding the use of TNF alpha in tumour therapy is systemic toxicity. The expression of membrane-bound (nonsecreted) TNF alpha within a tumour may serve to reduce systemic toxicity while retaining anti-tumour activity. Two adenovirus (Ad) vectors were constructed: (1) Ad-mTNF-wt expressing wild-type murine TNF alpha; and (2) Ad-mTNF-MEM expressing a mutant non-secreted (membrane-bound) form. Only the Ad-mTNF-wt vector induced high levels of TNF alpha secretion in transduced cells (approximately 400 ng/10(6) cells), however, both vectors induced efficient cell surface expression as detected by FACS. These vectors were used in tumour immunotherapy trials in a murine transgenic breast cancer model. High serum concentrations of mTNF alpha (approximately 1 ng/ml) were detected only in Ad-mTNF-wt-treated mice, while both vectors induced substantial disruption of tumour pathology. The wt TNF vector was highly toxic, killing 12 of 16 mice at a dose of 5 x 10(8) p.f.u., whereas the Ad-mTNF-MEM vector showed low toxicity killing three of 27 at the same dose. Both vectors induced partial, and in some cases, permanent tumour regressions, with cured mice displaying protective immunity and specific CTL activity against the tumour. These results indicate that the use of a nonsecreted form of TNF alpha can result in a relatively large reduction in systemic toxicity with little or no reduction in antitumour activity.

Adenoviridae↗
PubMed1996

Integrating public health information and surveillance systems.

The Centers for Disease Control and Prevention (CDC) recognizes sound public health information is the essential ingredient of all of its work and the key to effective public health decision making. A CDC/ATSDR committee reached a consensus that CDC needed to streamline and consolidate its public health surveillance and information systems into an integrated system. With integrated systems, a wide range of diverse individual information systems will continue to exist but these systems must be coordinated, interconnected, comparable, and easy to use. The "glue" that holds these systems together consists of (1) uniform data standards, (2) communications networks, and (3) policy-level agreements regarding data access, sharing, and reduction of data collection burdens. By putting the appropriate policy-making apparatus and resources in place, CDC believes the end result will be a streamlined process that meets the information needs of CDC and its partners with less confusion and frustration.

Humans↗
PubMed1984

Pregnancy and tuberculosis.

There is no solid evidence that pregnancy has an adverse effect on tuberculosis. With early diagnosis and prompt, adequate chemotherapy, the outcome of pregnancy in a woman with tuberculosis is likely to be good. Routine therapeutic abortion is not indicated. Data in the literature do not support the notion that pregnancy is a major risk factor for the development of tuberculosis, although no well-designed studies have been conducted. Screening of pregnant patients for tuberculosis should be based on consideration of other proved risk factors not on the fact of pregnancy. Preventive therapy should be given during the second and third trimesters of pregnancy to selected patients at high risk of progressive disease developing. Treatment of disease should be instituted promptly when disease is detected. The preferred regimens are INH-EMB, INH-RIF, or INH-EMB-RIF, although other drugs may be needed if the disease is recurrent or if there is resistance to these primary drugs. Mothers taking antituberculosis drugs can nurse their infants with little risk. With proper medical management, both tuberculosis and pregnancy can be expected to reach a happy conclusion in virtually all cases.

Drug Therapy, Combination↗