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Systemic immunosuppression induced by photodynamic therapy (PDT) is adoptively transferred by macrophages.

Some derivatives of hematoporphyrins are strongly retained by tumor tissue as compared to normal tissue, and exposure of these photosensitizers to radiation in the visible spectrum can cause serious biological damage. These properties have been exploited in the development of a new treatment for cancer termed photodynamic therapy (PDT). However, recent studies have also demonstrated that PDT can also induce a state of systemic immunosuppression. The purpose of this study was to determine whether PDT-induced suppression of contact hypersensitivity (CHS) responses was an active phenomenon that could be adoptively transferred by viable splenocytes from PDT-treated mice. Although induction of adoptively transferable suppressor cells in PDT-treated mice required exposure to antigen, the suppressor cells were found to be antigen nonspecific in their function. Furthermore, splenocytes from PDT-treated mice were capable of generating levels of allospecific cytotoxic T lymphocyte (CTL) activity which were comparable to those generated by normal control mice, but the ability of irradiated spleen cells from PDT-treated mice to stimulate a mixed lymphocyte response (MLR) was dramatically impaired. Finally, chromatographic separation of T cells, B cells and macrophages showed that the cell type which mediates adoptively transferable suppression of CHS responsiveness is in the macrophage lineage.

Animals↗

Correlation of natural killer cell activity and clearance of Cryptococcus neoformans from mice after adoptive transfer of splenic nylon wool-nonadherent cells.

Previous reports demonstrate that natural killer (NK) cells inhibit the growth of Cryptococcus neoformans in vitro, but conclusive evidence supporting the effectiveness of NK cells in host resistance to cryptococci is not available. The objective of these studies was to assess the ability of NK cells to clear C. neoformans from the lungs, livers, and spleens of infected mice. CBA/J mice were depleted of NK cells, as well as other natural effector cells, by an intraperitoneal injection of cyclophosphamide (Cy), 240 mg/kg of body weight. One day later, 7.5 X 10(7) nylon wool-nonadherent (NWN) spleen cells, either untreated or treated with anti-asialo GM1 and complement to remove NK cells, were adoptively transferred to Cy-pretreated mice. On day 2 after Cy treatment, the mice were injected intravenously with 2 X 10(4) cryptococci. At 4 and 6 days after Cy treatment, tissues were assayed for NK reactivity, using a 4-h 51Cr-release assay, and for in vivo clearance of cryptococci as reflected by mean log10 CFU per organ. We observed that Cy treatment depleted NK activity against YAC-1 targets and reduced in vivo clearance of C. neoformans from the tissues of infected mice. Additionally, Cy treatment depleted the total lung and spleen cellularity and the total number of peripheral blood lymphocytes when compared with those in normal untreated control mice. Also, spleen weights were significantly decreased in comparison with those of untreated animals 4 days after Cy treatment. Adoptive transfer of untreated NWN spleen cells into Cy-depressed mice restored the NK cell activity which correlated with enhanced clearance of cryptococci from lungs, livers, and spleens. In contrast, treatment of NWN spleen cells with anti-asialo GM1 and complement before adoptive transfer abrogated the ability of these cells to restore NK activity or reduce the numbers of cryptococci present in tissues of infected mice. Taken together, these data indicate that NK cells are the cells effective in diminishing the numbers of cryptococci in tissues of infected mice. Consequently, NK cells may play a role in first-line host resistance against C. neoformans.

Animals↗

Analysis of colony-stimulating factors and macrophage progenitor cells in mice immunized against Listeria monocytogenes by adoptive transfer.

Experiments were performed to elucidate the role of colony-stimulating factors in host defenses to the intracellular pathogen Listeria monocytogenes. Mice were protected against Listeria sp. by adoptive transfer of immune spleen cells and were then challenged with listeriae intravenously. Control mice were injected with spleen cells from uninfected mice. Adoptively immunized (immune) mice had significantly fewer listeriae in spleens and livers 2 and 4 days after Listeria challenge than did control mice. During acute infection, colony-stimulating activity in serum was increased earlier (10 h) in immune mice than in controls. Concentrations of colony-stimulating activity were equal at 24 h. By 48 h, values were decreased in immune mice, but were elevated in control mice. Similar changes were noted when a specific colony-stimulating factor, macrophage colony-stimulating factor, was measured in serum by using a radioimmunoassay. The changes in serum colony-stimulating activity in mice adoptively immunized with immune spleen cells were eliminated if spleen cells were first treated with anti-Thy-1.2 monoclonal antibodies. The number of macrophage progenitor cells in bone marrow and spleen were also determined as measures of the hemopoietic potential in these organs. The number of macrophage progenitor cells in bone marrow was higher in immune animals than control animals at 1, 2, and 4 days of infection. Similarly, the number of these cells in spleens was higher during the early stages of infection in immune mice. These results indicate that both the regulation of leukocyte production and the transfer of specific cellular immunity by spleen cells are associated, and they therefore suggest that hemopoietic regulatory factors play a role in immune host defenses.

Animals↗

Human DNA polymerase iota promotes replication through a ring-closed minor-groove adduct that adopts a syn conformation in DNA.

Acrolein, an alpha,beta-unsaturated aldehyde, is generated in vivo as the end product of lipid peroxidation and from oxidation of polyamines. The reaction of acrolein with the N2 group of guanine in DNA leads to the formation of a cyclic adduct, gamma-hydroxy-1,N2-propano-2'-deoxyguanosine (gamma-HOPdG). Previously, we have shown that proficient replication through the gamma-HOPdG adduct can be mediated by the sequential action of human DNA polymerases (Pols) iota and kappa, in which Poliota incorporates either pyrimidine opposite gamma-HOPdG, but Polkappa extends only from the cytosine. Since gamma-HOPdG can adopt either a ring-closed cyclic form or a ring-opened form in DNA, to better understand the mechanisms that Pols iota and kappa employ to promote replication through this lesion, we have examined the ability of these polymerases to replicate through the structural analogs of gamma-HOPdG that are permanently either ring closed or ring opened. Our studies with these model adducts show that whereas the ring-opened form of gamma-HOPdG is not inhibitory to synthesis by human Pols eta, iota, or kappa, only Poliota is able to incorporate nucleotides opposite the ring-closed form, which is known to adopt a syn conformation in DNA. From these studies, we infer that (i) Pols eta, iota, and kappa have the ability to proficiently replicate through minor-groove DNA lesions that do not perturb the Watson-Crick hydrogen bonding of the template base with the incoming nucleotide, and (ii) Poliota can accommodate a minor-groove-adducted template purine which adopts a syn conformation in DNA and forms a Hoogsteen base pair with the incoming nucleotide.

Acrolein↗

An analysis of the pacing strategy adopted by elite competitors in 2000 m rowing.

OBJECTIVES: To determine the pacing strategies adopted by elite rowers in championship 2000 m races. METHODS: Split times were obtained for each boat in every heavyweight race of the Olympic Games in 2000 and World Championships in 2001 and 2002, and the top 170 competitors in the British Indoor Rowing Championships in 2001 and 2002. Data were only included in subsequent analysis if there was good evidence that the athlete or crew completed the race in the fastest possible time. The remaining data were grouped to determine if there were different strategies adopted for on-water versus ergometer trials, "winners" versus "losers", and men versus women. RESULTS: Of the 1612 on-water race profiles considered, 948 fitted the inclusion criteria. There were no differences in pacing profile between winners and losers, and men and women, although on-water and ergometry trials showed a competitively meaningful significant difference over the first 500 m sector. The average profile showed that rowers performed the first 500 m of the race faster than subsequent sectors-that is, at a speed of 103.3% of the average speed for the whole race, with subsequent sectors rowed at 99.0%, 98.3%, and 99.7% of average speed for on-water rowing, and 101.5%, 99.8%, 99.0%, and 99.7% for ergometry. CONCLUSIONS: These data indicate that all athletes or crews adopted a similar fast start strategy regardless of finishing position or sex, although the exact pace profile was dependent on rowing mode. This strategy should be considered by participants in 2000 m rowing competitions.

Competitive Behavior↗

Adoptive therapies: quo vadis?

The success of adoptive immunotherapy using interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells in treating a percentage of patients with melanoma and renal cell carcinoma has provided impetus to research into both how to optimize this treatment as well as approaches into making immunotherapy in general more successful. As the question on how to optimize IL-2 dose, schedule, cell culture conditions, and other specifics of IL-2 plus LAK therapy are addressed in clinical trials, other approaches suggested by data from in vitro, animal, and the clinical studies using IL-2 are emerging into clinical trials. (table; see text) These include two major areas of focus at the present time: (1) the use of IL-2 +/- LAK in combination with a variety of agents which have been shown to be synergistic with it, including other biological response modifiers (such as interferons), agents which may act both as interferon inducers as well as by other mechanisms (poly-IC:LC and flavone-8-acetic acid), and chemotherapeutic agents (especially cyclophosphamide, doxorubicin and agents which have some activity against the disease being treated such as DTIC for melanoma), and (2) various approaches aimed at inducing and expanding tumor-specific immune cells which appear to have greater antitumor activity than LAK cells and which may be major contributors to the antitumor efficacy of IL-2 therapy. These approaches also have the potential benefit of inducing memory cells with a resultant long-term immune antitumor response. Approaches aimed at activating specific antitumor immune cells include the use of IL-2-expanded infiltrating lymphocytes from tumors, exposure of peripheral blood cells cultured in IL-2 to tumor cells to hopefully expand those with a specific antitumor response, and the use of tumor cell vaccines in conjunction with IL-2. In addition to approaches using activated and expanded LAK effectors or specific T cells, the potential role of activated (e.g. by gamma interferon) and expanded (e.g. by macrophage colony stimulating factor) macrophages in the adoptive immunotherapy of cancer remains an area of ongoing exploration both in preclinical studies and clinical trials. As a greater understanding of the antitumor mechanisms of IL-2 and LAK therapy and other forms of adoptive immunotherapy is achieved, therapeutic approaches can be defined which will maximize the ability to mediate the immune destruction of tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Alterations in pulmonary function in cancer patients receiving adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2.

Adoptive immunotherapy with tumor-infiltrating lymphocytes (TIL) and interleukin-2 (IL-2) is currently being investigated in the treatment of chemoresistant cancers. In protocols using high dosages of IL-2 and adoptive transfers of lymphokine-activated killer (LAK) cells, severe pulmonary toxicities, including pulmonary edema and respiratory failure, are regularly observed. Serial measurements of pulmonary function in patients receiving TIL and continuous infusions of moderate dosages of IL-2 showed the development of mild obstructive and restrictive defects. Partial reversibility of the FEV1 with bronchodilators was observed, suggesting the development of hyperreactive airways. Decreases in lung volumes, DLCO, and gas exchange occurred and may reflect pulmonary infiltration by inflammatory cells, increased lung water, or diminished chest wall function. We conclude that adoptive immunotherapy with TIL and IL-2 produces changes in systemic immune response that may contribute to abnormal pulmonary physiology.

Combined Modality Therapy↗

Institutional and economic influences on the adoption and extensiveness of managerial innovation in hospitals: The case of reengineering.

In the recent past, a number of managerial innovations--including product line management, total quality management, and reengineering--have swept through the hospital industry. Given their pervasiveness and their cost, understanding the mix of factors that influences their adoption is of theoretical interest and practical relevance. The research reported here focuses on this general question by examining influences on the adoption and extensiveness of a particular managerial innovation, hospital reengineering. The results suggest that while economic and institutional factors have influenced the adoption and extensiveness of hospital reengineering, institutional forces play a more important role. The greater influence of institutional forces may be attributed to the high degree of uncertainty in health care, the causal ambiguity of the innovation, and the anticipatory actions of hospitals attempting to position themselves in a rapidly changing environment.

Decision Making, Organizational↗

Explaining the adoption of telemedicine services: an analysis of a paediatric telemedicine service.

Since 1998, over 1300 telemedicine consultations have been provided to 12 schools in Kansas City. Despite the success of the programme, effective utilization of services has not occurred at all sites. We used a focus group and survey methods to investigate barriers to and catalysts for service adoption. The results showed that the school nurses strongly supported the programme. They valued its ability to provide health-care for the children and they welcomed their enhanced role. However, technical complexities and difficulties in obtaining parental consent were found to impede adoption. The nurses also expressed frustration with school personnel who had a poor understanding of their role in general as well as that of the telemedicine service. A new state reimbursement policy may promote greater understanding and provide a financial incentive for schools to adopt the telemedicine service.

Attitude of Health Personnel↗

Countering tobacco industry sponsorship of Hispanic/Latino organizations through policy adoption: a case study.

Restricted by Master Settlement Agreement (MSA) provisions, the tobacco industry employs corporate sponsorship of communities of color (e.g., sponsoring community cultural events and/or chambers of commerce) to secure their stronghold. The Hispanic/Latino Tobacco Education Network (H/LaTEN) initiated efforts to counter these marketing forms within the Hispanic community. In 1998, 38 California Hispanic Chambers of Commerce (CHCCs) were contacted to assess the tobacco industry's marketing tactics and penetration. CHCCs reported receiving tobacco funding in the past, making them susceptible to future protobacco industry influence. Subsequently, an intervention was implemented to inoculate the CHCCs against industry influence by encouraging an antitobacco corporate sponsorship policy adoption. Six CHCCs representing approximately 400 businesses in the community adopted this policy. Targeting susceptible organizations including and beyond the Hispanic community and advocating for an antitobacco corporate sponsorship policy adoption are strategies that can be used in tandem with MSA enforcement to effectively build resistance.

California↗

Adoption of a plant-based diet by patients with recurrent prostate cancer.

The Western diet has been associated with prostate cancer incidence as well as risk of disease progression after treatment. Conversely, plant-based diets have been associated with decreased risks. A pilot clinical trial of a 6-month dietary change and stress reduction intervention for asymptomatic, hormonally untreated patients experiencing a consistently rising PSA level, the first sign of recurrence of prostate cancer after surgery or radiation therapy, was conducted to investigate the level of intake of plant-based foods and the relationship between intake and the change in the rate of PSA rise. A pre-post design was employed in which each patient served as his own control. In this multifaceted intervention, patients and their spouses were encouraged to adopt and maintain a plant-based diet. The prestudy rate of PSA rise (from the time of posttreatment recurrence to the start of the study) was ascertained by review of patients' medical records. Dietary assessments were performed and prostate-specific antigen (PSA) levels ascertained at baseline, prior to the start of intervention, and at 3 and 6 months. Changes in numbers of servings of plant-based food groups were calculated and compared with rates of PSA rise over the corresponding time intervals. Median intake of whole grains increased from 1.7 servings/d at baseline to 6.9 and 5.0 servings/d at 3 and 6 months, respectively. Median intake of vegetables increased from 2.8 servings/d at baseline to 5.0 and 4.8 servings/d at 3 and 6 months, respectively. The rate of PSA rise decreased when comparing the prestudy period (0.059) to the period from 0 to 3 months (-0.002, P < .01) and increased slightly, though not significantly, when comparing the period from 0 to 3 months to the period from 3 to 6 months (0.029, P = .4316). These results provide preliminary evidence that adoption of a plant-based diet is possible to achieve as well as to maintain for several months in patients with recurrent prostate cancer. Changes in the rate of rise in PSA, an indicator of disease progression, were in the opposite direction as changes in the intake of plant-based food groups, raising the provocative possibility that PSA may have inversely tracked intake of these foods and suggesting that adoption of a plant-based diet may have therapeutic potential in the management of this condition.

Aged↗

Adoptive T cell therapy: Addressing challenges in cancer immunotherapy.

Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

Journal Article↗

Mental health, attachment and breastfeeding: implications for adopted children and their mothers.

Breastfeeding an adopted child has previously been discussed as something that is nice to do but without potential for significant benefit. This paper reviews the evidence in physiological and behavioural research, that breastfeeding can play a significant role in developing the attachment relationship between child and mother. As illustrated in the case studies presented, in instances of adoption and particularly where the child has experienced abuse or neglect, the impact of breastfeeding can be considerable. Breastfeeding may assist attachment development via the provision of regular intimate interaction between mother and child; the calming, relaxing and analgesic impact of breastfeeding on children; and the stress relieving and maternal sensitivity promoting influence of breastfeeding on mothers. The impact of breastfeeding as observed in cases of adoption has applicability to all breastfeeding situations, but may be especially relevant to other at risk dyads, such as those families with a history of intergenerational relationship trauma; this deserves further investigation.

Journal Article↗

Adoption and sustainability of decision support for patients facing health decisions: an implementation case study in nursing.

BACKGROUND: Effective interventions prepare patients for making values-sensitive health decisions by helping them become informed and clarifying their values for each of the options. However, patient decision support interventions have not been widely implemented and little is known about effective models for delivering them to patients. The purpose of this study was to describe call centre nurses' adoption of a decision support protocol into practice following exposure to an implementation intervention and to identify factors influencing sustainable nursing practice changes. METHODS: Exploratory case study at a Canadian province-wide call centre guided by the Ottawa Model of Research Use. Data sources included a survey of nurses who participated in an implementation intervention (n = 31), 2 focus groups with nurses, interviews with 4 administrators, and a document review. RESULTS: Twenty-five of 31 nurses responded to the survey measuring adoption of decision support in practice. Of the 25 nurses, 11 had used the decision support protocol in their practice within one month of the intervention. Twenty-two of the 25 intended to use it within the next three months. Although some nurses found it challenging to begin using the protocol, most nurses reported that it: a) helped them recognize callers needing decision support; b) changed their approach to handling these calls; and c) was a positive enhancement to their practice. Strategies identified to promote sustainability of practice changes included integration of the decision support protocol in the call centre database, streamlining the patient decision aids for easier use via telephone, clarifying the administrative direction for the call centre's program, creating a call length guideline specific for these calls, incorporating decision support training in the staff development plan, and informing the public of this enhanced service. CONCLUSION: Although most nurses adopted the decision support protocol for coaching callers facing values-sensitive decisions, to sustain practice changes, interventions are required to manage barriers in the practice environment and integrate decision support into the organization's policies, resources, and routine activities.

Journal Article↗

Rates of euthanasia and adoption for dogs and cats in Michigan animal shelters.

Estimates of canine and feline euthanasia at U.S. animal shelters--largely based on voluntary surveys with low response rates--make it difficult to estimate the population from which the euthanized animals derive. Estimates of euthanasia rates (animals euthanized per unit of population) have varied widely and been available only sporadically. This study used requirements of Michigan state law (Pet Shops, Dog Pounds, and Animal Shelters Act, 1969) for animal shelters to collect admission and discharge data for all 176 Michigan-licensed animal shelters. In 2003, Michigan shelters discharged 140,653 dogs: Of these, 56,972 (40%) were euthanized; 40,005 (28%) were adopted. This annual euthanasia rate is 2.6% of the estimated 2003 Michigan dog population. Michigan shelters discharged 134,405 cats in 2003: 76,321 (57%) by euthanasia and (24%) by adoption. The estimated ratio of euthanized cats to cats who had owners was 3.1%. Small shelters and privately owned shelters were associated with higher adoption rates. Comparison with historical information from the past 10 to 20 years suggests the number of companion animals being euthanized in shelters has decreased and that progress has been made in reducing the companion animal overpopulation problem.

Animal Husbandry↗

Asymmetric distribution of the C. elegans HAM-1 protein in neuroblasts enables daughter cells to adopt distinct fates.

One mechanism of generating cellular diversity is to distribute developmental potential asymmetrically to daughter cells at mitosis. Two observations described in this report suggest that the C. elegans HAM-1 protein functions in dividing neuroblasts to produce daughter cells that adopt distinct fates. First, HAM-1 is asymmetrically distributed to the periphery of certain mitotic cells, ensuring that it will be inherited by only one daughter cell. Second, ham-1 mutations disrupt the asymmetric divisions of five neuroblasts. In one of these divisions, loss of ham-1 function causes the daughter cell that does not inherit HAM-1 to adopt the fate of the daughter cell that normally inherits HAM-1. We propose that asymmetric distribution of HAM-1 enables daughter cells to adopt distinct fates.

Animals↗

The adoption and diffusion of ambulatory care retirement housing communities.

This article is the result of an exploratory study into the factors slowing the adoption of a retirement housing community. Through research, we have identified a list of primary issues which are impeding the movement of the retirement housing community concept from the introductory stage of the product life cycle into its growth stage. We have then related each of the issues to the general factors which serve to accelerate the adoption rate and provided suggestions concerning specific strategies that will overcome each of the factors slowing the adoption rate.

Aged↗

Acknowledging barriers in adopting person-centered planning.

An apparent contradiction in adopting person-centered planning is exemplified by the question "If a system adopts person-centered planning, isn't it system-centered"? Such ambiguities are obvious to employees, who increasingly are being asked to consider more personalized ways of assisting people through person-centered planning. Our premise in this article is that employees' reservations are well-founded and should be addressed in order to facilitate understanding and eventual reconciliation of unavoidable conflicts that emerge when person-centered planning is undertaken by agency employees. Administrators who acknowledge the uncertainties accompanying person-centered planning and invite discussion about conceptual and practical difficulties inherent in its adoption are modeling a collaborative method of discovering ways to help people get what they need. Examples of group solutions are presented.

Humans↗