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Biomedical subjects

D Wiley

Publications and source records attributed to D Wiley.

13 recordsLinked to original sources

Decreased recovery of CD4 lymphocytes in older HIV-infected patients beginning highly active antiretroviral therapy.

Among virological responders, the area under the curve of the CD4 count minus baseline (AUCMB) after 3, 9, 15 and 18 months of highly active antiretroviral therapy (HAART) was less in individuals 55 years or older (P < 0.05). Fewer older individuals achieved increases of 50, 100, or over 150 CD4 cells/l. A random quadratic time course model estimated that the AUCMB decreased 35 cells/year for each 10 years of additional age during the first 12 months after HAART (P < 0.005).

Aged↗

Hyperthermic resuscitation is safe and effective after hemorrhagic shock in dogs.

OBJECTIVE: To show that resuscitation from hypothermic, hemorrhagic shock using 65 degrees C intravenous fluid results in a more rapid return to euthermia compared with 40 degrees C intravenous fluid, without significant endothelial or hemolytic injury. DESIGN: Fourteen anesthetized beagles (10-12 kg) were cooled to a core temperature of 30 degrees C and hemorrhaged to a mean arterial pressure of 40 to 45 mm Hg for 30 minutes. The animals were randomized to receive either 65 degrees C or 40 degrees C intravenous fluid through a specially designed catheter at a rate of 80% of their blood volume per hour until euthermic (37 degrees C) or for 2 hours. MATERIALS AND METHODS: Blood pressure, pulmonary artery pressure, heart rate, and core temperature were continuously monitored. Blood samples were collected at baseline, after hemorrhage, 2 hours of resuscitation, and at postmortem examination after 7 days of survival. Laboratory measurements included complete blood count, plasma-free hemoglobin, and osmotic fragility. Values were compared using the Student's paired or unpaired t test with p approximately 0.05 indicating significance. Postmortem examination included light microscopy of the proximal superior vena cava or right atrium. RESULTS: Animals receiving 65 degrees C intravenous fluid warmed 3.6 degrees C/hour, significantly faster than the 40 degrees C animals (1.9 degrees C/hour). There were no significant differences in plasma-free hemoglobin or osmotic fragility. Endothelial injuries were found in two animals in each group. These defects occurred along the path of catheter insertion and not at the infusion site. CONCLUSIONS: Central intravenous fluid at 65 degrees C is a more rapid means of treating hypothermia than standard 40 degrees C intravenous fluid. It is safe even in hypovolemic animals.

Animals↗

A comparison of two controlled-release delivery systems for the delivery of amiloride to control angiogenesis.

The diuretic amiloride has been reported to inhibit both Na+-H+ antiport and the urokinase-type plasminogen activator. As a consequence of these inhibitions, neovascularization may also be inhibited. We hypothesized that if amiloride could be effectively delivered in a site-specific manner, a system might be developed that could inhibit localized angiogenesis. In order to evaluate this possibility we conducted a study that compared two different controlled-release systems into which amiloride had been incorporated. The effectiveness of amiloride release from each delivery system was determined by quantitating angiogenic patterns in a chick chorioallantoic membrane (CAM) system using a fractal analysis software program. The two delivery systems compared were sucrose acetate isobutyrate (SAIB) and calcium alginate. Initial HPLC laboratory tests confirmed that amiloride could be released from both SAIB and calcium alginate in vitro in a sustained manner for 72 h. The CAM studies confirmed that neither SAIB nor calcium alginate alone promoted or inhibited angiogenesis when compared to nontreated controls. The release of amiloride from each delivery vehicle resulted in a significant (P < 0.05) inhibition of angiogenesis following both 24 and 48 h of release compared to controls. There was no difference in inhibition of angiogenesis, however, when comparing SAIB + amiloride treated CAMs with calcium alginate + amiloride treated CAMs. These data suggest that both SAIB and calcium alginate may be useful delivery vehicles for the localized application of amiloride to control angiogenesis. Such a system could potentially control tumor angiogenesis without systemic effects.

Alginates↗

Sexual function in 1,202 aging males: differentiating aspects.

BACKGROUND: Late-life sexuality is an important quality-of-life issue that has been minimally explored. This survey seeks to extend our knowledge of the relationship of sexual attitudes and preferences to sexual functioning of a large group of older, community-dwelling men. METHODS: Older men aged 58-94 (N = 1,202) were surveyed with an anonymous self-administered questionnaire including 63 items regarding present and past, actual and desired sexual practices and attitudes. RESULTS: Although age correlated consistently with increased erectile dysfunction and decreased sexual activity, a substantial number of older men continued active sexual behaviors supported by positive attitudes toward sexual function. It was found that both health status and perceived partner's responsiveness are prominent moderators of the age effect. CONCLUSION: In the absence of social isolation and health issues, many older men show persistently active sexual lifestyles as evidenced in their interest and participation in sexual activities. These findings negate a portion of the starkly negative imagery of sexual expression in aging males.

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Persistently seronegative men from whom HIV-1 has been isolated are genetically and immunologically distinct.

Studies in both monkeys and humans have suggested that transient infection with HIV-1 can occur without provoking a measurable humoral immune response. The objective of this study was to look for genetic and immunologic correlates of transient HIV-1 infection in antibody-negative men from whom HIV-1 had been isolated. The distributions of MHC class I, class II, and TAP (transporter protein associated with antigen processing) region genes were compared between 23 persistently seronegative men from whom HIV-1 was isolated at least once (isol+/Ab-) and 137 men who seroconverted. A subset of 13 of the 23 isol+/Ab- men were compared to 27 seronegative men for distribution of CD25+CD4+ and CD25+CD8+ cells in the absence of exogenous immunologic stimulation. The prevalences of the TAP1.4, and a combination of TAP1.4, and TAP2.3 variants were significantly higher in the isol+/Ab- men. The proportion of CD8+ cells that expressed CD25+ antigen was also significantly higher in the isol+/Ab- men than in the seronegative men. We conclude that isol+/Ab- men may be genetically and immunologically distinct from HIV-1 susceptible men. We hypothesize that activated CD8+ cells may have cleared HIV-1 infection in these men through genetically mediated influences of the TAP genes on the presentation of peptides by HLA class I molecules.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Sexuality and aging--usual and successful.

BACKGROUND: As aging research increasingly reflects an effort to dissociate true time-driven changes from those that can be improved, sexuality in later life remains largely unexplored. Several problems are evident. There is a lack of normative data, a lack of a conceptual framework relating to the biology, psychology, and sociology of sex, and an attitudinal resistance that obscures the entire topic. METHODS: We conducted a three-part instructional series on major topics involved with sexuality and aging. We surveyed our group of attendees (n 158, average age 68 for males, 65 for females) before and after the series. RESULTS: A remarkably robust sex life was evidenced by both the men and the women, even until advanced old age. Yet, a substantially decreased involvement was reported from 10 years earlier. Despite current activities, people of both sexes wished they were participating even more than they currently were. Impotency was identified as the major negative feature for the men; relationship problems were for the women. A questionnaire 6 months after the series reported improved sexual attitudes, but no change in sexual activities from the earlier survey. CONCLUSION: Sexuality is a major quality-of-life issue which persists into old age. Our study showed that the usual sexual practices reported by our group were not considered by them to be ideal. The intervention of this instructional series provided improved sexual attitudes but not performance. Additional studies are encouraged.

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Variant specific glycoprotein of Trypanosoma brucei consists of two domains each having an independently conserved pattern of cysteine residues.

The complete amino acid sequences for nine variant specific glycoproteins (VSGs) of Trypanosoma brucei are presented. These have more than doubled the size of the VSG sequence data base and have enabled a new and more rigorous comparison to be made between amino acid sequences of different VSGs. Each VSG can be defined as a combination of an N-terminal domain type and a C-terminal domain type, based on the distribution of cysteine residues within the molecule. This identifies three N-terminal domain types and at least four C-terminal domain types. Different combinations of N and C-terminal domains can be formed; for example, in the sequences presented here, two different N-terminal domains are found in association with each of three different C-terminal domains. The biological context of the domain structure of VSGs is discussed.

Amino Acid Sequence↗

2.9 A resolution structure of the N-terminal domain of a variant surface glycoprotein from Trypanosoma brucei.

The variant surface glycoprotein (VSG) of Trypanosoma brucei forms a coat on the surface of the parasite; by the expression of a series of antigenically distinct VSGs in the surface coat the parasite escapes the host immune response. The 2.9 A resolution crystal structure of the N-terminal domain of one variant, MITat 1.2, has been determined. The structure was solved using data collected from two crystal forms. Initially a partial model was built into an electron density map based on multiple isomorphous replacement phases and improved by phase combination methods. Subsequently this model was used to obtain the molecular replacement solution for a second crystal form, providing starting phases which were refined using 2-fold non-crystallographic symmetry averaging. The current model includes 362 residues and has been refined using X-PLOR to an R value of 0.22 for data between 7 and 2.9 A. The molecule is a dimer, approximately 100 A long, having an asymmetrical cross section with maximum dimensions of approximately 40 A x 60 A. Two long, approximately 70 A, alpha-helices from each monomer pack together to form, with several other helices, a core helix bundle that extends nearly the full length of the molecule. The "top" of the protein, which in the surface coat may be exposed to the external environment, is formed from the ends of the two long helices, a short three-stranded beta-sheet, and a strand having irregular conformation that packs above these secondary structure elements. Two conserved disulfide bridges are in this part of the molecule. Several elements of the MITat 1.2 sequence, which contribute to the formation of the helix bundle structure, have been identified. These elements can be found in the sequences of several different VSGs, suggesting that to some extent the VSG structure is conserved in those variants.

Amino Acid Sequence↗