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PubMed1985

Antibody levels in adoptively immunized mice after infection with Babesia microti or injection with antigen fractions.

Specific IgG anti-Babesia antibodies could be detected by an ELISA test in the serum of adoptively immunized mice which subsequently were infected with Babesia microti. Initially, higher IgG antibody levels were present in the recipients of either untreated immune spleen cells or mitomycin C-treated immune spleen cells compared with the values in control mice which received the infection alone. Subsequently, a marked anamnestic response occurred only in mice which received untreated immune spleen cells and not in the recipients of mitomycin C-treated cells, demonstrating a requirement for proliferation of B memory cells in the anamnestic response. When mice were injected with either T or B enriched spleen cell subpopulations and infected with B. microti, the anamnestic antibody response in each animal correlated well with protection against infection. The stimulation of the adoptively transferred immune spleen cells in recipient mice by injection of B. microti antigen fractions prepared by DEAE cellulose chromatography increased the level of antibody production and protection against infection in these mice. A highly significant correlation between these two parameters could be demonstrated for certain antigen fractions.

Animals↗
PubMed2005

Adoption of an official ISEA glossary.

The International Society for Exposure Analysis (ISEA) and its Nomenclature Committee have been involved since the mid-1990s in an intermittent but ongoing effort to develop an official ISEA glossary. Several related activities have stimulated greater interest and discussion nationally and internationally on a common exposure language. Among these activities are a 1997 Journal of Exposure Analysis and Environmental Epidemiology feature article on exposure and dose definitions and a 1999-initiated project of the International Programme on Chemical Safety (IPCS) (WHO/ILO/UNEP) to confront terminology issues hindering harmonization in the area of exposure assessment. Recently, the ISEA members voted in support of adopting the IPCS glossary as the official ISEA glossary, and the ISEA Executive Board agreed to accept this recommendation. In this feature article, we (1) describe the process through which the ISEA adopted the IPCS glossary as the official ISEA glossary, (2) present the joint IPCS/ISEA glossary of terms and their definitions, and (3) discuss plans for how the glossary can be used by ISEA and updated over time by ISEA and IPCS. The glossary is intended to be a living document that reflects the latest usage and maintains international harmonization of exposure terminology that can be practically applied to improve communication in exposure and related fields.

Environmental Exposure↗
PubMed1997

Synthetic putative transmembrane region of minimal potassium channel protein (minK) adopts an alpha-helical conformation in phospholipid membranes.

Minimal potassium channel protein (minK) is a potassium channel protein consisting of 130 amino acids, possessing just one putative transmembrane domain. In this study we have synthesized a peptide with the amino acid sequence RDDSKLEALYILMVLGFFGFFTLGIMLSYI, containing the putative transmembrane region of minK, and analysed its secondary structure by using Fourier-transform IR and CD spectroscopy. The peptide was virtually insoluble in aqueous buffer, forming intermolecular beta-sheet aggregates. On attempted incorporation of the peptide into phospholipid membranes with a method involving dialysis, the peptide adopted a predominantly intermolecular beta-sheet conformation identical with that of the peptide in aqueous buffer, in agreement with a previous report [Horvàth, Heimburg, Kovachev, Findlay, Hideg and Marsh, (1995) Biochemistry 34, 3893-3898]. However, by using an alternative method of incorporating the peptide into phospholipid membranes we found that the peptide adopted a predominantly alpha-helical conformation, a finding consistent with various proposed structural models. These observed differences in secondary structure are due to artifacts of aggregation of the peptide before incorporation into lipid.

Amino Acid Sequence↗
PubMed1998

The octapeptide angiotensin II adopts a well-defined structure in a phospholipid environment.

The conformational properties adopted by angiotensin II in a phospholipid micelle solution were studied by NMR spectroscopy and molecular modelling. The octapeptide was found to assume a well-defined hairpin structure with its C- and N-termini approaching to within 0.76 nm of each other. Three of the residues had fixed side chain configurations; Tyr4 (g+), His6 (g-) and Val3 (g-). Consequently, the His6 and Tyr4 aromatic rings were consistently close together. Conformers containing a cis His6-Pro7 peptide bond were observed for the peptide in a purely aqueous sample but completely disappeared when lipid vesicles were added to the sample. This result is explained by the existence of a very stable hydrogen bond between the Phe8 NH and the His6 carbonyl group of the lipid-solvated trans isomer, resulting in the formation of an inverse gamma turn centered on Pro7. 1H-NMR selective line broadening was apparent for several of the angiotensin II protons upon titration of an aqueous sample with less than stoichiometric amounts of 1,2-dimyristoyl-sn-glycero-3-phosphocholine bilayer vesicles. The data obtained were consistent with the structure derived for micelle-bound angiotensin II, indicating that conformations adopted by the peptide hormone in the presence of micelles and lipid-bilayer vesicles are similar.

Angiotensin II↗
PubMed2000

Adoptive transfer of nuclear factor-kappaB-inactive macrophages to the glomerulus.

BACKGROUND: Macrophages have been regarded as "blackguards" in the generation of glomerular injury. However, it is still unclear what kind of cellular machinery is responsible for their pathogenic actions. To explore this issue, this investigation aims at developing a novel strategy using adoptive transfer of "loss-of-function" macrophages to the glomerulus. As a prototypal investigation, this study examines a role for nuclear factor-kappaB (NF-kappaB) in effector actions of macrophages within the glomerular microenvironment. METHODS: NF-kappaB-inactive macrophages, NIKMACNR, were created by transduction of NR8383 rat macrophages with retrovirus encoding a super-repressor mutant of IkappaBalpha, IkappaBalphaM. The effector functions of NIKMACNR cells on resident cells were evaluated by coculture, cross-feeding, and in vivo macrophage transfer. RESULTS: Rat mesangial cells cocultured with control macrophages showed abundant expression of activation markers, including monocyte chemoattractant protein-1, stromelysin, and gelatinase B. In contrast, coculture with NIKMACNR macrophages induced only modest gene expression. Similarly, culture medium conditioned by activated, control macrophages triggered mesangial cells and isolated glomeruli to express the activation markers, whereas the stimulatory effect was not observed in medium conditioned by NIKMACNR macrophages. To evaluate effector actions of NIKMACNR macrophages in the glomerulus, control macrophages and NIKMACNR cells were transferred into normal rat glomeruli via renal artery injection. After the transfer of control macrophages, substantial induction of the activation marker stromelysin was observed in resident glomerular cells. This induction was dramatically diminished in the glomeruli transferred with NIKMACNR macrophages. CONCLUSIONS: Inactivation of NF-kappaB in macrophages effectively disrupted paracrine, stimulatory loops from macrophages to resident glomerular cells. A combination of "loss-of-function" strategies with the technique for adoptive cell transfer is thus useful to explore pathophysiologic roles for certain machinery of macrophages within the glomerulus.

Animals↗
PubMedDate not supplied

Tinea capitis due to Trichophyton soudanense in Cincinnati, Ohio, in internationally adopted children from Liberia.

Two sisters, ages 5 and 6 years, who were adopted from Liberia, presented in Cincinnati, Ohio, with tinea capitis. Fungal cultures grew Trichophyton soudanense, a dermatophyte rarely seen in North America. Both girls had multiple other infections. They responded well to therapy with oral griseofulvin and topical selenium sulfide. With the current increase in international travel and adoption, nonendemic dermatophyte infections such as this need to be recognized.

Antifungal Agents↗
PubMed2001

Adopting the qualitative paradigm to understanding children's perspectives of illness: barrier or facilitator?

Reliance on the traditional quantitative paradigm has been the norm for exploring the phenomenon of children's illness experiences. Although it provides valuable information on the psychosocial sequelae of children in response to illness, an account of children's perspectives of the illness experience is missing. Accordingly, researchers since the early 1980s have been advocating the need to adopt the qualitative paradigm in the study of children's illness experiences. Nonetheless, even though there is a call for more qualitative research, the majority of research being conducted today still supports the quantitative paradigm. This report examines why researchers may be reluctant to adopt the qualitative paradigm. Specifically, the author proposes that this reluctance may stem from researchers' perceiving children as being less competent and social than adults, which would explain the need to research children solely from an objective, impersonal stance. Primary philosophical principles of the qualitative paradigm may be seen as barriers to accessing children's thoughts. The author suggests, however, that when children are viewed from an alternative perspective, the major principles of the qualitative paradigm may actually serve as facilitators to apprehending their thoughts and feelings. The following key principles of the qualitative research paradigm are examined: (a) realities are constructed by human beings who are viewed as active agents making sense out of the realities they encounter; (b) realities are multiple and must be perceived holistically and from various vantage points; and (c) realities are shared and mutually shaped by the researcher and research participants. Key strategies that promote successful use of the qualitative paradigm in the study of children's illness experiences are also discussed.

Attitude of Health Personnel↗
PubMed1987

Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer.

Adoptive immunotherapy involving bolus-dose recombinant interleukin-2 (rIL-2) has been reported to induce tumor regression in some patients with cancer, but has been associated with severe fluid retention and cardiopulmonary stress. In an effort to preserve the efficacy but reduce the toxicity of this treatment, we used escalating doses of rIL-2 as a constant infusion rather than as a bolus dose. Forty-eight patients with advanced cancer received rIL-2 as a 24-hour infusion in five-day cycles separated by five-day periods of rest and leukapheresis. Eight patients were removed from the study before receiving cells activated in vitro. In the 40 who could be evaluated for their response, there were 13 partial responses (32.5 percent) and 2 minor responses. Partial responses were observed in Hodgkin's disease (one of one), non-Hodgkin's lymphoma (one of one), lung cancer (one of five), ovarian cancer (one of one), parotid cancer (one of two), renal cancer (three of six), and melanoma (five of ten). Responses were associated with a good performance status, a base-line lymphocyte count above 1400 per cubic millimeter, and an rIL-2-induced lymphocyte count of at least 6000. Optimal lymphocytosis required a priming dose of rIL-2 of 3 X 10(6) U per square meter of body-surface area per day, and 15 of 28 patients receiving this priming dose responded to treatment. A weight gain of more than 10 percent of total body weight (five patients) and dyspnea at rest (six patients) were unusual events restricted to patients with poorer pretreatment performance. We conclude that the administration of rIL-2 as a constant infusion may preserve the antineoplastic activity of adoptive immunotherapy while increasing the safety and comfort of patients.

Adult↗
PubMed1989

The effect of the Medicare prospective payment system on the adoption of new technology. The case of cochlear implants.

Since the advent of Medicare's prospective payment system, beneficial but cost-increasing medical advances have been systematically assigned to existing diagnosis-related groups (DRGs) that do not cover the costs of the new technology. Recent evidence suggests that such underpayment reduces the rate at which hospitals adopt that technology. Safeguards designed to offset the negative incentives of underpayment, including the recalibration of DRG values, update factors, and the allowance of Medicare profits, appear not to have worked. We studied the case of cochlear implantation. Years after Food and Drug Administration approval and a favorable decision about Medicare coverage, payment for the device remains well below its average cost, and many hospitals ration the availability of the device to Medicare patients because of the financial losses involved. Eventually, so few patients received the implant that the original manufacturer discontinued its production. Under the DRG system, negative payment incentives compete with clinical considerations when hospitals and physicians decide whether to adopt specific cost-increasing new forms of technology of proved value. Other payment mechanisms that do not insert arbitrary financial considerations into specific treatment decisions should be considered instead.

Centers for Medicare and Medicaid Services, U.S.↗
PubMed2005

The extracellular region of ErbB4 adopts a tethered conformation in the absence of ligand.

The human ErbB family of receptor tyrosine kinases comprises the epidermal growth factor receptor (EGFR/ErbB1/HER1), ErbB2 (HER2/Neu), ErbB3 (HER3), and ErbB4 (HER4). ErbBs play fundamental roles in cell growth and differentiation events in embryonic and adult tissues, and inappropriate ErbB activity has been implicated in several human cancers. We report here the 2.4 A crystal structure of the extracellular region of human ErbB4 in the absence of ligand and show that it adopts a tethered conformation similar to inactive forms of ErbB1 and ErbB3. This structure completes the gallery of unliganded ErbB receptors and demonstrates that all human ligand-binding ErbBs adopt the autoinhibited conformation. We also show that the binding of neuregulin-1beta to ErbB4 and ErbB3 and the binding of betacellulin to both ErbB4 and ErbB1 does not decrease at low pH, unlike the binding of epidermal growth factor and transforming growth factor-alpha to ErbB1. These results indicate an important role for ligand in determining pH-dependent binding and may explain different responses observed when the same ErbB receptor is stimulated by different ligands.

Adult↗
PubMed2006

Disulfide cross-linking indicates that FlgM-bound and free sigma28 adopt similar conformations.

The dissociable sigma subunit of bacterial RNA polymerase is required for the promoter-specific initiation of transcription. When bound to RNA polymerase, sigma makes sequence-specific promoter contacts and plays a crucial role in DNA melting. In isolation, however, sigma lacks significant promoter binding activity. In the crystal structure of the flagellar sigma factor, sigma(28), bound to the anti-sigma factor, FlgM, sigma(28) adopts a compact conformation in which the promoter binding surfaces are occluded by interdomain contacts. To test whether sigma(28) adopts this conformation in the absence of FlgM, we engineered a set of double cysteine mutants predicted to form interdomain disulfides in the conformation observed in the FlgM complex. We show that these disulfides form in both the presence and absence of FlgM. For two of the mutants, quantitative measurements of disulfide formation under equilibrium conditions suggest that the major solution conformation favors disulfide formation. The results indicate that the compact conformation of sigma(28) observed in the sigma(28)/FlgM structure is similar to the predominant conformation of free sigma(28) in solution. This finding suggests that autoinhibition of DNA binding in free sigma(28) is accomplished by steric occlusion of the promoter binding surfaces by interdomain interactions within the sigma factor as well as by a suboptimal distance between the promoter -10 and -35 element binding determinants in sigma(2) and sigma(4), respectively.

Amino Acid Substitution↗
PubMed1994

Technology and older adults: factors affecting the adoption of automatic teller machines.

Although technology can benefit service providers, caregivers, and the elderly, its application in an aging society can bring special challenges. This study looked at older adults' adoption of one technology that is highly prevalent in modern society--the automatic teller machine (ATM). The findings indicated that users and nonusers differed in mechanical reasoning skills and in attitudes toward ATM technology. Older adults with higher mechanical reasoning skills were more likely to be ATM users. Nonusers had more negative attitudes toward ATMs, and, among nonusers, those who had tried an ATM had more positive attitudes than those who had never tried one. The findings of this study are discussed in terms of factors that may affect the adoption of other technologies by older adults. Suggestions for increasing the acceptance of technologies by the elderly are also addressed.

Aged↗
PubMed2000

Identifying male college students' perceived health needs, barriers to seeking help, and recommendations to help men adopt healthier lifestyles.

Seven focus groups at a university campus were formed to identify college men's health concerns, barriers to seeking help, and recommendations to help college men adopt healthier lifestyles. Content analysis was used to identify and organize primary patterns in the focus-group data. Results of the study revealed that the college men were aware that they had important health needs but took little action to address them. The participants identified both physical and emotional health concerns. Alcohol and substance abuse were rated as the most important issues for men. The greatest barrier to seeking services was the men's socialization to be independent and conceal vulnerability. The most frequently mentioned suggestions for helping men adopt healthier lifestyles were offering health classes, providing health information call-in service, and developing a men's center. Implications of the results are discussed.

Adaptation, Psychological↗
PubMedDate not supplied

Adoption of assistive technology for computer access among college students with disabilities.

PURPOSE: Fourteen college students with disabilities identified factors that influenced them to adopt or reject Assistive Technology (AT) for the personal computer in order to assess the effectiveness of a college course on adapted computer use. METHOD: Forty-eight items were developed for a Q sort to represent both positive and negative statements in each of the three areas of Scherer's' model (milieu, person and technology). The model was modified to include specific statements about the training experience. A series of three interviews were administered to the students during the year following completion of the class. RESULTS: Factor analysis of the Q sorts indicated that the participants had a unanimously positive experience. Three factors ('a positive experience', 'I'm OK, you're not OK', and 'support') emerged from the Q sort analysis. The training programme, the technology provided, and the characteristics of the individuals in the class all seemed to contribute to the success of the experience. Seventy-five percent of the students who took the class adopted at least some of the AT a year later. CONCLUSIONS: This study supports the need for specific training programmes and course work for college students with disabilities who are interested in improving computer access skills.

Adolescent↗
PubMed2005

Differences in dentists' working postures when adopting proprioceptive derivation vs. conventional concept.

New technologies and changes in dental care, including the proprioceptive derivation (Pd) concept, aimed at providing dentists with greater comfort and better health, were introduced in Thailand. The aim of this study was to investigate the differences in dentists' working postures when adopting different work concepts: Pd and the conventional concept. The results showed differences in dentists' sitting posture, clock-related working positions, and Rapid Upper Limb Assessment (RULA) scores. This implied that Pd helped dentists to discover new ways of positioning themselves, and working comfortably and effectively, which made it possible for them to adopt better working posture and have lower RULA scores. In conclusion, the Pd concept had a positive effect on dentists' working posture.

Adaptation, Physiological↗
PubMedDate not supplied

Optimal lifting techniques adopted by Chinese men when determining their maximum acceptable weight of lift.

The purpose of this study was to identify biomechanically the mechanisms adopted by Chinese men when they psychophysically determined their MAWLs (maximum acceptable weights of lift) in different tasks. Twenty-two healthy Chinese men determined their MAWLs at two lifting vertical ranges and three lifting frequencies. Peak L5/S1 compressive forces, elbow and shoulder peak reactive moments, acceleration effects, and postures were analyzed throughout the lifting acts. The results showed that different lifting techniques were adopted when determining the MAWL at different vertical ranges and frequencies of lifting. Posture analyses showed that a more stooped technique was used in frequent tasks, which would minimize the metabolic cost. For infrequent tasks, subjects accelerated and lifted the load upward and then shortened the moment arm by flexing the elbow and shoulder joints during landing, to compensate for weakness of the upper extremities. The high prelifting acceleration used during the infrequent tasks caused high compressive forces on the L5/S1 disc. These results emphasize the importance of considering the roles of upper extremity strength when designing lifting tasks for Chinese workers.

Acceleration↗
PubMed1971

Antigen modulation of the immune response. The effect of delayed challenge on the affinity of anti-dinitrophenylated bovine gamma globulin antibody produced in adoptive recipients.

Secondary immune responsiveness to dinitrophenylated bovine gamma globulin (DNP-BGG) was transferred to heavily irradiated rats by means of small lymphocytes from the thoracic duct of immunized syngeneic donors. Affinity of the antibody produced by the adoptive recipients when challenged immediately was the same as that seen in immunized controls and cell donors, suggesting that the performance of lymphocytes in the thoracic duct of immunized rats provide an accurate measure of the immunologic history of memory cells both in the intact animal and the lymphocyte-depleted donor. The relevance of this to cell cooperation in the production of antibody to hapten-protein complexes is discussed. Direct evidence on antigen modulation of the immune response was also obtained. When immune thoracic duct lymphocytes were transferred to adoptive recipients and challenged either immediately or after a delay of 6 wk, it was found that, although the amount of antibody decreased with this delay in challenge, the affinity remained constant. Thus it would seem that in control rats, the increase in the affinity of antibody with time after immunization is, in fact, due to the selection of new populations of cells by the progressively waning concentration of antigen.

Animals↗
PubMed1972

Immunopathogenesis of acute central nervous system disease produced by lymphocytic choriomeningitis virus. II. Adoptive immunization of virus carriers.

Lymphocytic choriomeningitis (LCM) virus carriers were established by intracerebral inoculation of adult BALB/c mice followed by a single dose of cyclophosphamide (CY) (150 mg/kg) 3 days after infection, and by intracerebral injection within 24 hr of birth. These carriers were then adoptively immunized with spleen cells or serum from immune or normal BALB/c donors. Transfer of immune spleen cells into drug-induced carriers consistently resulted in acutely fatal choriomeningitis, histologically strikingly similar to classical LCM. Normal spleen cells or immune serum failed to produce either central nervous system (CNS) pathology or illness with any regularity. In addition, focal necrosis of the cerebellum was seen after adoptive immunization of drug-induced carriers but only when mice received cells at least 3 wk after inoculation, which is probably explained by the gradual spread of infection from membranes to the neural parenchyma during the first month after establishment of the carrier state in adult mice. Immune spleen cells, when transferred to neonatal carriers, led to a decrease in virus titers in blood and brains and to development of antibody without acute CNS disease. It appears that the production of fatal choriomeningitis after LCM infection is determined in part by the distribution of viral antigen, and this is markedly different in neonatal and drug-induced carriers at the time of cell transfer. Another factor of potential importance is the much higher level of circulating viral antigen in the plasma of neonatal than in that of drug-induced LCM carriers. Classical LCM disease can only be transferred by immune lymphoid cells and not by antiserum. Furthermore, little or no complement-fixing (CF) antibody was found in the plasma of mice dying of acute choroiditis. These observations strongly suggest that acute choroiditis is dependent upon the cell-mediated immune response.

Animals↗