HIV-1 candidate vaccines can induce antibodies which share specificity with human monoclonal antibodies capable of neutralizing primary isolates.
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AIDS Vaccines↗
Biomedical subjects
D Davis
Publications and source records attributed to D Davis.
Dosage effects on gene expression in a maize ploidy series.
Previous studies on gene expression in aneuploids revealed numerous trans-acting dosage effects. Segmental aneuploidy of each varied chromosomal region exhibited predominantly inverse effects on several target genes. Here, dosage regulation was examined in a maize (Zea mays L.) ploidy series where the complete genomic complement is varied. Total RNA from leaf tissue of monoploid, diploid, triploid, and tetraploid plants (1x, 2x, 3x, and 4x, respectively) was analyzed for the expression of 18 genes. For most tested genes, the transcript level per cell is directly proportional to structural gene dosage; that is, on a per genome basis, there is approximately equal expression among the four ploidies. Exceptional cases show a negative correlation of expression with ploidy or a positive correlation greater than expected from the structural gene dosage. These studies suggest that, in general, as structural gene dosage increases in multiples of the monoploid complement, the absolute level of gene expression per cell increases. In contrast, addition or subtraction of only a single chromosome arm tends to alter gene expression patterns extensively. The combined results of the euploid and aneuploid studies suggest that aneuploid effects result from an altered stoichiometry of the factors contributing to the mechanisms of gene expression.
Blotting, Northern↗
Literature and ethical medicine: five cases from common practice.
This essay is composed of five stories written by practicing physicians about their patients. Each clinical story describes a challenging ethical condition-potential abuse of medical power, gravely ill and probably over-treated newborns, iatrogenic narcotic addiction, deceived dying people. Rather than singling out one ethical conflict to resolve or adjudicate, the authors attempt, through literary methods, to grasp the singular experiences of their patients and to act according to the deep structures of their patients' lives. Examining these five stories with simple literary tools-attention to narrative frames, time, plot, and desire-reveals the mechanisms through which acts of writing and reading contribute to clinical clarity and ethical actions.
Adult↗
Least restrictive alternatives: do they really work?
Seclusion and restraint continue to spark debate regarding their therapeutic value and ethical, legal, and humanitarian implications, yet they remain frequently used forms of treatment in psychiatric settings. Identifying specific alternatives to seclusion and restraint use, teaching nursing staff how and when to use them, and determining their effect on patient outcome are important quality improvement issues. A quality improvement study conducted at a long-term care psychiatric facility identified alternatives that nursing staff used and their effect on reducing seclusion and restraint rates. A total of 773 incidents of disruptive behavior were managed with least restrictive alternatives and did not require the use of seclusion or restraint. One-to-one verbal intervention followed by medication as needed represented the most frequently used alternative. Total seclusion and restraint hours decreased by 31 percent, and restraint hours decreased by 47 percent.
Colorado↗
Progressive familial leukodystrophy of late onset.
We report a family in which three siblings developed dementia between the ages of 40 and 70 years. Two of the siblings developed symptoms of depression, abnormal behavior, and an inability to function, progressing to severe dementia. The third sibling had a severe dementia, the clinical details of which are not available. In the two deceased siblings neuropathologic examinations demonstrated severe demyelination, axon loss, and gliosis in cerebral white matter. Cerebellar and brainstem white matter were unaffected. Cerebral gray matter was negligibly affected. The disorder, histopathologically classified as a pigmented orthochromatic leukodystrophy, is extremely rare. Its etiology is unknown, but the pathology and familial occurrence imply that it represents a genetic defect in a function localized in the cerebral white matter.
Adult↗
Changing behavior. Practical lessons from the diabetes control and complications trial.
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Attitude to Health↗
A survey of gunshot residue analysis methods.
A survey was sent to 80 forensic laboratories in 44 States and two Canadian Provinces concerning methodology in analyzing gunshot residue (GSR) and interpreting the results. Of the 80 surveys, 50 (63%) were returned completed. Questions included standard procedures, collection methods, thresholding problems and specificity of data. These results are compared to a previous survey reported in 1990. Implications for the interpretation and future study of these methods are discussed.
Data Collection↗
Mouse model for the lysosomal disorder galactosialidosis and correction of the phenotype with overexpressing erythroid precursor cells.
The lysosomal storage disorder galactosialidosis results from a primary deficiency of the protective protein/cathepsin A (PPCA), which in turn affects the activities of beta-galactosidase and neuraminidase. Mice homozygous for a null mutation at the PPCA locus present with signs of the disease shortly after birth and develop a phenotype closely resembling human patients with galactosialidosis. Most of their tissues show characteristic vacuolation of specific cells, attributable to lysosomal storage. Excessive excretion of sialyloligosaccharides in urine is diagnostic of the disease. Affected mice progressively deteriorate as a consequence of severe organ dysfunction, especially of the kidney. The deficient phenotype can be corrected by transplanting null mutants with bone marrow from a transgenic line overexpressing human PPCA in erythroid precursor cells. The transgenic bone marrow gives a more efficient and complete correction of the visceral organs than normal bone marrow. Our data demonstrate the usefulness of this animal model, very similar to the human disease, for experimenting therapeutic strategies aimed to deliver the functional protein or gene to affected organs. Furthermore, they suggest the feasibility of gene therapy for galactosialidosis and other disorders, using bone marrow cells engineered to overexpress and secrete the correcting lysosomal protein.
Abnormalities, Multiple↗
Report on activities and attitudes of organizations active in the clinical practice guidelines field.
The organizing committee of a workshop on clinical practice guidelines (CPGs) surveyed invited organizations on their attitudes and activities related to five topics to be covered during the workshop sessions: organizational roles, priority setting, guidelines implementation, guidelines evaluation and development of a network of those active in the CPG field. Organizational roles: The national specialty societies were felt to have the largest role to play; the smallest roles were assigned to consumers, who were seen to have a role mainly in priority setting, and to industry and government, both of which were seen to have primarily a funding role. Many barriers to collaboration were identified, the solutions to all of which appeared to be better communication, establishment of common principles and clear role definitions. Priority setting: There was considerable agreement on the criteria that should be used to set priorities for CPG activities: the burden of disease on population health, the state of scientific knowledge, the cost of treatment and the economic burden of disease on society were seen as important factors, whereas the costs of guidelines development and practitioner interest in guidelines development were seen as less important. Organizations were unable to give much information on how they set priorities. Guidelines implementation: Most of the organizations surveyed did not actively try to ensure the implementation of guidelines, although a considerable minority devoted resources to implementation. The 38% of organizations that implemented guidelines actively listed a wide variety of activities, including training, use of local opinion leaders, information technology, local consensus processes and counter detailing. Guidelines evaluation: Formal evaluation of guidelines was undertaken by fewer than 13% of the responding organizations. All the evaluations incorporated assessments before and after guideline implementation, and some used primary patient data. Barriers to evaluation included lack of money, time, data or expertise. CPG Network: Most of the respondents felt that all organizations and individuals interested or involved in guidelines should form the membership of the network. The three most important functions of such a network were deemed to be (a) to facilitate collaboration among those involved in the CPG process, (b) to maintain an information centre on CPGs and (c) to provide expertise to the CPG process. It was felt that the network should have some formal structure and communicate through e-mail and print media.
Attitude↗
Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements.
Fusion genes encoding the 3' part of the can gene are implicated in two types of leukemia. The dek-can fusion gene is present in t(6;9) acute myeloid leukemia and the set-can fusion gene is present in one case of acute undifferentiated leukemia. In order to obtain leads towards the molecular basis of these diseases, we have studied the cellular localization of the DEK-CAN and SET-CAN fusion proteins and their normal counterparts. DEK-CAN and SET-CAN were localized exclusively in the nucleus, and also DEK and SET were found to be nuclear proteins. However, CAN was mainly located at the nuclear and cytoplasmic face of the nuclear envelope. This observation is in accordance with the presence of an amino acid repeat in the C-terminal part of CAN, common to the family of nucleoporins. The C-terminal part also contains a nuclear location domain as shown by deletion analysis. This domain may be important for the presence of CAN at the nucleoplasmic side of the nuclear envelope. The relocation of the carboxyterminal part of CAN due to DEK-CAN and SET-CAN may reinforce a nuclear function of the CAN protein.
Acute Disease↗
Correlation of rapid changes in the average water diffusion constant and the concentrations of lactate and ATP breakdown products during global ischemia in cat brain.
Rapid changes in the average water diffusion constant, Dav = 1/3[Dxx+Dyy+Dzz], and in the concentrations of lactate and purine nucleotides and nucleosides were measured upon global ischemia (cardiac arrest) in cat brain, at a combined time resolution of 36 s (n = 7). At this time resolution, the normalized time curves of 1 - Dav and the increase in ATP breakdown product did not coincide, with the changes in Dav being most rapid. The normalized curves of 1 - Dav and the lactate increase coincided for the first 2-2.5 min after which the change in Dav was more rapid. After this time point, an excellent correlation was found between the drop in Dav and the decrease in energy utilization rate, which was calculated from the measured time curves of lactate formation and ATP breakdown, and from the time curve for phosphocreatine use reported in the literature. These results are in agreement with the expected biphasic changes in ion and water homeostasis during ischemia and with the model of diffusional changes being a consequence of a water shift from interstitial to intracellular space.
Adenosine Triphosphate↗
Serological diagnosis of feline immunodeficiency virus infection using recombinant transmembrane glycoprotein.
We developed an antibody detection enzyme-linked immunosorbent assay (ELISA) using recombinant surface (SU), transmembrane (TM) and capsid (CA) antigens of feline immunodeficiency virus (FIV) expressed in Escherichia coli. The three antigens were tested with sera collected from experimentally infected cats in order to follow the course of seroconversion and of the antibody levels throughout the infection. An early and marked increase of TM antibodies was observed. Antibodies to TM were demonstrated at high levels throughout the observation period. The immune response to SU and to CA was less pronounced and in some cats the level of antibodies to SU and CA tended to decline 6 months after infection. In addition, 413 FIV negative and positive cat sera were tested in order to define for each antigen the diagnostic sensitivity, specificity and efficiency. TM showed the highest diagnostic sensitivity (98%) while its specificity was 97%. Its diagnostic efficiency of 97% was better than that of SU and CA and exceeded that of tests utilizing conventionally grown and gradient purified FIV. Therefore, recombinant TM can be considered a very important antigen for FIV ELISA testing. An interesting perspective is offered in the combination of TM with other recombinant antigens in a dot assay form.
Animals↗
FIV vaccine studies. I. Immune response to recombinant FIV env gene products and outcome after challenge infection.
We have vaccinated five groups of cats (n = 25) four times with five preparations of recombinant feline immunodeficiency virus (FIV) env gene products; one group (n = 7) served as control. The vaccine formulations were as follows: (1) envelope glycoprotein of FIV Zurich 2 (FIV Z2) expressed in a Baculovirus system and isolated by gel electroelution (denatured form); (2) insect cells expressing FIV Z2 glycoprotein; (3) envelope glycoprotein of a Boston strain (FIV Bangston) expressed in insect cells and isolated by gel electroelution (denatured form); (4) glycosylated Bangston envelope protein made in insect cells and isolated in a native form; (5) non-glycosylated Bangston envelope protein made in Escherichia coli. All cats were challenged with 20 50% cat infective doses (CID50) of FIV Z2 previously titrated in cats. All vaccinated cats developed high enzyme-linked immunosorbent assay (ELISA) antibodies to the homologous antigen; crossreactivity to heterologous antigens was seen at a lower level. Virus neutralizing antibodies (tested with Petaluma virus) reached titers up to 32. After challenge, all cats seroconverted (as judged by anti gag antibodies in Western blot) and became infected (as judged by virus isolation and/or polymerase chain reaction) between 4 and 11 weeks with the exception of one cat. It is concluded that it is relatively easy to induce high ELISA antibody titers using recombinant env gene products, ELISA antibody titers do not correlate with virus neutralization or with protection.
Animals↗
An experimental chemically inactivated HIV-1 vaccine induces antibodies that neutralize homologous and heterologous viruses.
We have developed a unique multiple step procedure to inactivate human immunodeficiency virus chemically with a very high safety margin while retaining antigenically active structural virion proteins, including gp120, in the final immunogen. The whole virus preparation (1-10 micrograms per dose) was highly immunogenic in a variety of small mammals and induced antibodies that recognized homologous and heterologous strains of HIV-1. Sera from immunized animals bound to peptides representing the entire sequence of the external glycoprotein gp120. Neutralizing antibodies active against the homologous immunizing strain and against heterologous HIV-1 strains were also elicited. Sera with virus neutralizing activity did not bind to MHC class I proteins derived from the human cell line used to grow the virus.
AIDS Vaccines↗
Independent practice: a critical analysis and a personal journey.
This paper describes the personal journey of one independent practitioner as she moved from the environment of hospital practice and training to that of an independent practitioner. Many of the difficulties encountered on this journey can best be understood by reflection on the social, historical and political context in which nursing, midwifery and women experience their world. Critical theory offers midwifery the opportunity to more fully understand our worlds and to move beyond the dominant social order and reconstruct our social worlds in more just and liberating ways.
Australia↗
Ways of knowing in midwifery.
Scientific ways of knowing dominate our society today and this has major ramifications for midwifery. This article outlines the historical development and cultural understanding of ways of knowing in our society today. It is suggested that the patriarchal societies in which our ways of knowing have developed have emphasised scientific ways of knowing while other ways such as intuition and embodied knowledge received little acknowledgement. This article then goes on to explore these other ways of knowing, discusses their implications for midwifery care and suggests that to embrace many and varied ways of knowing is to more fully realise our abilities and potential as midwives.
Cultural Characteristics↗
Lymphocytotropic strains of HIV type 1 when complexed with enhancing antibodies can infect macrophages via Fc gamma RIII, independently of CD4.
Antipeptide sera raised against the gp120/gp41 sequences of human immunodeficiency virus type 1 (HIV-1) were used to determine their capacity to enhance infection. Antisera to the five variable regions (V1 to V5) of gp120 and conserved parts of gp120 and gp41 facilitated infection of primary human macrophages with the homologous virus HIV-1 SF2mc. In contrast, heterologous virus infection with HTLV-IIIB was mediated only by antisera to the conserved regions, predominantly C4 and C5. Heterologous virus infection occurred more rapidly and was consistent between different cell donors. The neutralizing monoclonal antibody (MAb) SC258 (murine IgG2a) but not MAb 684-238 (mIgG1) against conformational epitopes of the V2 region also induced antibody-dependent infection enhancement (ADE). Therefore, preincubation with certain antibodies can cause altered tropism of the lymphocytotropic viruses mentioned above. Viral infection was completely abolished by preincubation with the F(ab)2 fragment of MAb 3G8 against the Fc gamma receptor III (CD16). A MAb (7.3F11) against the gp120-binding site of CD4 had no effect on viral infectivity. Possible mechanisms and their implications for disease progression are discussed.
Acquired Immunodeficiency Syndrome↗
Increased middle cerebral artery flow velocity during the initial phase of cardiopulmonary bypass may cause neurological dysfunction.
One hundred twenty-seven patients undergoing coronary artery bypass graft surgery were monitored by transcranial Doppler ultrasonography. Five patients had more than 50% increases in middle cerebral artery mean flow velocity during the initial phase (10-120 sec) of cardiopulmonary bypass. Four of these 5 developed neurological complications including stroke and encephalopathy. These results indicate that overperfusion of the basal cerebral arteries during cardiopulmonary bypass procedures may contribute to neurological dysfunction after the surgery.
Adult↗