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Biomedical subjects

C C Wilson

Publications and source records attributed to C C Wilson.

At least 37 records · Page 2Linked to original sources

Overlapping epitopes in human immunodeficiency virus type 1 gp120 presented by HLA A, B, and C molecules: effects of viral variation on cytotoxic T-lymphocyte recognition.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are thought to exert immunologic selection pressure in infected persons, yet few data regarding the effects of this constraint on viral sequence variation in vivo, particularly in the highly variable Env protein, are available. In this study, CD8+ HIV type 1 (HIV-1) envelope-specific CTL clones specific for gp120 were isolated from peripheral blood mononuclear cells of four HIV-infected individuals, all of which recognized the same 25-amino-acid (aa) peptide (aa 371 to 395), which is partially contained in the CD4-binding domain of HIV-1 gp120. Fine mapping studies revealed that two of the clones optimally recognized the 9-aa sequence 375 to 383 (SFNCGGEFF), while the two other clones optimally recognized the epitope contained in the overlapping 9-aa sequence 376 to 384 (FNCGGEFFY). Lysis of target cells by the two clones recognizing aa 375 to 383 was restricted by HLA B15 and Cw4, respectively, whereas both clones recognizing aa 376 to 384 were restricted by HLA A29. Sequence variation, relative to the IIIB strain sequence used to identify CTL clones, was observed in autologous viruses in the epitope-containing region in all four subjects. However, poorly recognized autologous sequence variants were predominantly seen for the A29-restricted clones, whereas the clones specific for SFNCGGEFF continued to recognize the predominant autologous sequences. These results suggest that the HLA profile of an individual may not only be important in determining the specificity of CTL recognition but may also affect the ability to recognize virus variants and suppress escape from CTL recognition. These results also identify overlapping viral CTL epitopes which can be presented by HLA A, B, and C molecules.

Cytotoxicity, Immunologic↗

Hydrogen-Atom Ordering in Lead Hydrogen Arsenate Monitored by Neutron Time-of-Flight Laue Diffraction using Single-Frame Methods.

The ordering of the hydrogen atom in a single crystal of lead hydrogen arsenate in the temperature range 320 to 80 K is described. The details of the ordering at small temperature steps are determined from single frames of data collected using the neutron time-of-flight Laue method. The constrained refinements obtained from these data yield lower precision than full data sets but allow the ordering to be characterized rapidly and reliably. This is the first example of the use of this single-frame method of monitoring such phase transitions. The approach used here with neutrons, stimulated in part by synchrotron Laue diffraction, will be of interest for all time-resolved experiments with synchrotron radiation or neutrons.

Journal Article↗

DNA hydration studied by neutron fiber diffraction.

The development of neutron high angle fiber diffraction to investigate the location of water around the deoxyribonucleic acid (DNA) double-helix is described. The power of the technique is illustrated by its application to the D and A conformations of DNA using the single crystal diffractometer, D19, at the Institut Laue-Langevin. Grenoble and the time of flight diffractometer, SXD, at the Rutherford Appleton ISIS Spallation Neutron Source. These studies show the existence of bound water closely associated with the DNA. The patterns of hydration in these two DNA conformations are quite distinct and are compared to those observed in X-ray single crystal studies of two-stranded oligodeoxynucleotides. Information on the location of water around the DNA double-helix from the neutron fiber diffraction studies is combined with that on the location of alkali metal cations from complementary X-ray high angle fiber diffraction studies at the Daresbury Laboratory SRS using synchrotron radiation. These analyses emphasize the importance of viewing DNA, water and ions as a single system with specific interactions between the three components and provide a basis for understanding the effect of changes in the concentration of water and ions in inducing conformational transitions in the DNA double-helix.

Crystallography↗

Time-of-flight Laue fiber diffraction studies of perdeuterated DNA.

The diffractometer SXD at the Rutherford Appleton Laboratory ISIS pulsed neutron source has been used to record high resolution time-of-flight Laue fiber diffraction data from DNA. These experiments, which are the first of their kind, were undertaken using fibers of DNA in the A conformation and prepared using deuterated DNA in order to minimise incoherent background scattering. These studies complement previous experiments on instrument D19 at the Institut Laue Langevin using monochromatic neutrons. Sample preparation involved drawing large numbers of these deuterated DNA fibers and mounting them in a parallel array. The strategy of data collection is discussed in terms of camera design, sample environment and data collection. The methods used to correct the recorded time-of-flight data and map it into the final reciprocal space fiber diffraction dataset are also discussed. Difference Fourier maps showing the distribution of water around A-DNA calculated on the basis of these data are compared with results obtained using data recorded from hydrogenated A-DNA on D19. Since the methods used for sample preparation, data collection and data processing are fundamentally different for the monochromatic and Laue techniques, the results of these experiments also afford a valuable opportunity to independently test the data reduction and analysis techniques used in the two methods.

Crystallography↗

Ex vivo expansion of CD4 lymphocytes from human immunodeficiency virus type 1-infected persons in the presence of combination antiretroviral agents.

Expansion of CD4 lymphocytes from human immunodeficiency virus type 1 (HIV-1)-infected persons ex vivo has been limited by enhanced virus replication and cell death. The successful expansion of functional CD4 lymphocytes from HIV-1-infected persons has now been accomplished using a bispecific monoclonal antibody to CD3 and CD8 in combination with three antiretroviral agents. CD4 lymphocytes were polyclonally expanded by a factor of 10(3)-10(7) during 4-8 weeks in culture. Supernatants from most cultures were persistently HIV-1 p24 antigen-negative by day 14 and remained negative despite removal of antiretroviral agents at day 28. In such cultures, HIV-1 could not be recovered by cocultivation, and amounts of HIV-1 DNA declined or remained stable at low levels, eventually becoming undetectable in 2 cases. This approach establishes the feasibility of CD4 lymphocyte expansion in persons with HIV disease and may be useful for immune-based or gene therapies.

Acquired Immunodeficiency Syndrome↗

Transient reduction in hippocampal serotonergic innervation after neonatal parachloroamphetamine treatment.

This study examined the effects of parachloroamphetamine on neonatal forebrain serotonergic (5-HT) innervation. Rat pups were treated with PCA on P3 and P4. Significant reductions in 5-HT content were observed in the hippocampal formation, frontal cortex and entorhinal cortex on P5 and P7. By P14, neocortical 5-HT had returned to normal levels while hippocampal 5-HT values remained less than control. Hippocampal 5-HT content reached normal range by P21. High affinity 5-HT uptake in hippocampal synaptosomal preparations was similarly reduced on P5 and P7 suggesting that 5-HT terminals were being lesioned by PCA. 5-HT uptake recovered significantly by P14 perhaps reflecting the extraordinary plasticity of the 5-HT projections in the neonate. However, in contrast to the complete restoration of hippocampal 5-HT content, 5-HT uptake values remained significantly less than control. No change in 5-HT content was observed in either the hypothalamus or midbrain raphe at any age studied. Thus, the rapid onset of effects, regional selectivity and transient reduction of 5-HT levels recommend the use of PCA in studies of the role of 5-HT in hippocampal development.

Aging↗

Calcium channel blockers in the treatment of hypertension.

Physicians need to weigh the efficacy, adverse effects and cost of first-line antihypertensive agents. Calcium channel blockers lower blood pressure, improve coronary blood flow and depress cardiac contractility by relaxing smooth muscle and cardiac muscle. They have beneficial or neutral effects in hypertensive patients with angina, asthma, chronic obstructive pulmonary disease, postural hypotension, peripheral vascular disease, depression, sexual dysfunction, diabetes and hyperlipidemia. The major adverse effect of some calcium channel blockers is that they may worsen congestive heart failure in some patients. Because calcium channel blockers are metabolized in the liver, the dosage must be lowered in the elderly and in patients with hepatic disease. Diltiazem, verapamil and nifedipine represent prototypes of the three classes of calcium channel blockers, each with slightly different effects.

Calcium Channel Blockers↗

State unit on aging involvement with continuing care retirement community (CCRC) legislation.

State units on aging (SUAs) from 29 states with continuing care retirement community (CCRC) legislation were surveyed to (a) assess staff familiarity with CCRC legislation, (b) examine interdepartmental working relationships surrounding such legislation and ask what role(s) ombudspersons are playing in CCRC oversight, (c) determine what role(s) aging units have had in developing legislation, and (d) gain insights regarding legislative impact. Results indicate that SUAs have been active in legislative development but vary greatly in the intensity of their involvement with the implementation and enforcement of CCRC regulation and in their perception of legislative impact.

Aged↗

Accommodation and relocation decision making in continuing care retirement communities.

Accommodations and relocations in continuing care retirement communities (CCRCs) affect the lives of staff and residents. This article defines the CCRC concept and reviews the literature relevant to accommodation and relocation changes within CCRCs. Implications for health and human services practitioners who work with older CCRC residents, along with specific issues, are discussed.

Aged↗

The pet as an anxiolytic intervention.

The effect of a pet on psychological consequences of stress (i.e., state and trait anxiety levels) of college students was examined under three test conditions (i.e., reading aloud, reading quietly, and interacting with a friendly but unknown dog). A repeated-measures analysis of variance with three covariates was used to examine the effect of the treatment on each dependent variable (state and trait anxiety). Reading aloud differed from baseline measure under all treatment conditions (p less than .001). Reading quietly and interacting with the dog were slightly below baseline for variables, with more effect seen by reading quietly than by interacting with the dog. Examination of interactions among variables showed no significant differences. Effects upon state anxiety were significant, while trait anxiety levels remained fairly constant throughout the treatments. Baseline differences in trait anxiety scores indicate a potentially greater benefit for pet owners than nonowners. Selected social network and relationship data related to the role of the pet during anxiety-producing times were also analyzed. While interaction with the pet produced a decrease in anxiety level, pet owners did not report the use of their own pet as a social support (i.e., as confidant) significantly more than did previous owners. Results indicated that interacting with a pet for some individuals does affect both physiological and psychological responses by lowering response levels. However, a parallel effect was also seen by reading quietly. Given the effect of pet interaction upon selected social support indicators of health in well college students, these data suggest the importance of examining this treatment with an "at-risk" group in which it is possible to control for ownership characteristics.

Adolescent↗

Lessons from the implementation of CCRC regulation.

Oversight staff in 23 of the 30 states with legislation regulating continuing care retirement communities (CCRCs) completed a questionnaire surveying features of implementation experience such as problems encountered with the scope of regulation, the appropriateness of oversight placement, the adequacy of staff and financial resources, the use of discretionary agency authority, and attitudes toward various changes in applicable state law. These findings have relevance for consumers, legislators, lobbyists, and professionals working to make CCRCs a responsible long-term care alternative.

Aged↗

CCRC statutes: the oversight of long-term care service delivery.

A 1987 national survey revealed 27 states with continuing care or life care legislation. State oversight staff in 22 states responded to questions concerning characteristics of the regulated continuing care retirement community (CCRC) industry, the regulation of health and human service delivery within CCRCs, and interdepartmental working relationships between oversight agencies and other state units. Discussion focuses on the regulation of long-term care service provision in the CCRC industry.

Aged↗

Psychogenic amnesia.

Psychogenic amnesia is a psychiatric disorder characterized by sudden loss of memory in the absence of organic lesion or disease. The disorder most frequently occurs in association with a severe stressor, such as a natural disaster or military conflict. To facilitate effective treatment and an accurate prognosis, psychogenic amnesia must be differentiated from amnesia of structural or pharmacologic origin. Treatment may involve supportive psychotherapy, behavioral modification or pharmacotherapy. Prognosis for complete recovery is generally good.

Adult↗

Analysis of conformational parameters in nucleic acid fragments. IV. Intercalating drug complexes of very short chain oligonucleotides.

Studies have been made of base-pairing conformational parameters in single crystal structures of very short chain oligonucleotide structures complexed with drug molecules, using data extracted from the Cambridge structural database. The planar portion of the drug has a tendency to intercalate between two bases, utilising strong stacking interactions to stabilise the configuration. The effect of the existence of a formative backbone is seen in the high occurrence of standard base-pairing schemes and a consistent C1'-C1' separation, although the choice of compounds studied does tend to emphasise complementary pairing. In addition to the modulation of the general magnitude which is reduced from that in uncomplexed oligonucleotides, there appears to be some correlation of propeller twist value with the presence of planar groups sandwiching a base-pair. The average twist in such sandwiched pairs is lower than in any other group studied to date.

Base Composition↗

Analysis of conformational parameters in nucleic acid fragments. III. Very short chain oligonucleotides. The effect of base stacking.

Studies have been made of conformational parameters in single crystal structures of very short chain oligonucleotides consisting of strands with lengths in the range 2-3 bases. Using published data extracted from the Cambridge structural database for 20 such structures, a total of 14 base-pairs were found, of which 10 were hetero-pairs and 4 homo-pairs. Subjecting these to analysis to examine hydrogen bond parameters, propeller twist, buckle and C1'-C1' separation revealed an average propeller twist of 11.6 degrees, with no dependence of this parameter on hydrogen bonding details. In addition, an analysis of base stacking showed there to be no correlation between in-plane geometry and degree of inter-plane overlap.

Base Composition↗