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Biomedical subjects

J A Simpson

Publications and source records attributed to J A Simpson.

At least 55 records · Page 3Linked to original sources
PubMed1998

Quantitation of vancomycin and its crystalline degradation product (CDP-1) in human serum by high performance liquid chromatography.

The delayed clearance of vancomycin results in accumulation of vancomycin crystalline degradation product, CDP-1, in the bodies of renally impaired patients. The 2 isomers, CDP-1-M (major) and CDP-1-m (minor), of CDP-1 are antibiotically inactive but cross-react with some immunoassays that use polyclonal antibodies resulting in falsely elevated results. A high performance liquid chromatographic (HPLC) method was developed to quantitate vancomycin and CDP-1 in the serum of renal patients. After solid phase extraction of 200 microliters serum, the separation of vancomycin, the 2 isomers of CDP-1 and the internal standard (cefazolin) was accomplished by gradient HPLC on a reversed phase C18 column with detection at 210 nm. Linearity was established from 1 to 25 and 25 to 100 micrograms ml-1 vancomycin and 1 to 25 micrograms ml-1 CDP-1. Coefficients of variation for vancomycin and CDP-1 were 3.3-8.6% (n = 10) and 2.8-5.2% (n = 8).

Cefazolin↗
PubMed1998

Characteristics of Plasmodium vivax-infected erythrocyte rosettes.

To investigate the rosette formation properties of Plasmodium vivax, blood was sampled from 26 adult Thai patients admitted with acute P. vivax malaria and a predominance of trophozoite and schizont stages in their peripheral blood smears. In each case, P. vivax-infected cells formed spontaneous rosettes with two or more uninfected red blood cells. Rosette formation of P. vivax was dependent on the divalent cations (Ca2+/Mg2+) and was highly sensitive to trypsin and heparin, but, unlike P. falciparum, rosettes of P. vivax did not reform after removal of heparin. Plasma taken from patients with either acute uncomplicated P. falciparum or P. vivax malaria reversed rosette formation of all P. vivax isolates whereas plasma from uninfected controls had no effect. There was a small but significant increase in rosette-reversing activity in plasma taken during the convalescent period (P < 0.001). The increment in reversal activity was significantly greater in plasma taken following recovery from P. vivax malaria compared with P. falciparum malaria. This suggests that P. vivax rosette reversal activity is antibody mediated and has both species-specific and cross-species components.

Animals↗
PubMed1997

Adult attachment styles, the desire to have children, and working models of parenthood.

College students who had yet to marry and begin a family were asked about their desire to have children and their beliefs and expectations about themselves as parents (Study 1) and the characteristics of their prospective children (Study 2). Persons with more avoidant and anxious-ambivalent models of close adult relationships harbored more negative models of parenthood and parent-child relationships. These findings indicate that working models of parenting and parent-child relationships form well before marriage and the birth of children and that these models are systematically associated with attachment styles in adult relationships. The findings also suggest ways in which insecure attachments between child and parent may be influenced by the caregiver's models of parenting and parent-child relationships.

Adolescent↗
PubMed1996

Conflict in close relationships: an attachment perspective.

This study investigated how perceptions of current dating partners and relationships change after people with different attachment orientations attempt to resolve a problem in their relationship. Dating couples were videotaped while they tried to resolve either a major or a minor problem. Confirming predictions from attachment theory, men and women who had a more ambivalent orientation perceived their partner and relationship in relatively less positive terms after discussing a major problem. Observer ratings revealed that more ambivalent women who tried to resolve a major problem displayed particularly strong stress and anxiety and engaged in more negative behaviors. Conversely, men with a more avoidant orientation were rated as less warm and supportive, especially if they discussed a major problem. These results are discussed in terms of how highly ambivalent and highly avoidant people differentially perceive and respond to distressing events.

Adolescent↗
PubMed1996

Prognostic significance of Ki-67 and p53 immunoreactivity in cutaneous squamous cell carcinomas.

In this retrospective study we have investigated the expression of Ki-67 and p53 in 175 random cases of cutaneous squamous cell carcinomas by using the monoclonal antibodies MIB-1 and DO-1, respectively. The expression of these antibodies was compared with various histological parameters of prognostic significance. The staining results were also compared with the clinical outcome of the patients. MIB-1 and DO-1 staining showed statistically significant correlation with histopathological grade of the tumor (p < 0.0001 and p = 0.0016, respectively). The degree of immunolabelling of these antibodies also showed significant correlation with tumor depth and tumor thickness (MIB-1 thickness p = 0.02 and depth p = 0.026, and DO-1 thickness p = 0.014 and depth p = 0.005). The majority of the squamous cell carcinomas in our series were Clark's level IV, which therefore did not correlate with the extent of immunoreactivity (MIB-1, p = 0.098; and DO-1, p = 0.885). Mean length of clinical follow-up was 5.2 years. Aggressive tumor behaviour was seen in 17 patients (10.6%) with 6.9% and 3.4% local recurrences and nodal metastasis respectively. A total of 89.4% patients remained disease-free following their definitive surgical treatment. Vulval skin represented the commonest site associated with unfavourable clinical outcome (five of 17 cases). A large number of squamous cell carcinomas in this poor prognosis group showed a high prevalence of immunoreactivity of the antibodies but this did not achieve any statistical significance. We conclude that Ki-67 and p53 expression in cutaneous squamous carcinoma is not an independent predictor of prognosis.

Biomarkers, Tumor↗
PubMed1994

Effects of different weight loss treatments on weight cycling and metabolic measures in male mice.

The effects of different weight loss treatments on subsequent weight regain, food efficiency, body composition, metabolic rate, and corticosterone concentrations were investigated in obese male B6D2F1 mice. Treatment groups were: restricted (RES, food restricted); exercised (EX, treadmill exercised); sham control (SHAM, treadmill exposure, not exercised); lab chow control (LC). Weight loss, regardless of treatment, resulted in increased rate of weight regain and food efficiency. There were significant alterations in body composition after a cycle of weight gain/loss. These results demonstrate that a cycle of weight gain/loss causes increased food efficiency and concomitant alterations in body composition in male mice.

Animals↗
PubMed1993

Protein-bound 3,4-dihydroxyphenylalanine is a major reductant formed during hydroxyl radical damage to proteins.

Proteins and aromatic amino acids previously exposed to hydroxyl radicals reduced cytochrome c, free iron, and copper ions. A major product of hydroxyl radical addition to tyrosine is 3,4-dihydroxyphenylalanine (DOPA), which has these reducing properties. The reduction of nitro blue tetrazolium by radical-damaged protein was consistent with the generation of quinones in the protein. By acid hydrolysis followed by high-performance C18 reversed-phase liquid chromatography we have shown that hydroxyl radical-damaged proteins contain significant amounts of protein-bound DOPA (PB-DOPA). The authenticity of the DOPA measured was confirmed by gas chromatography-mass spectrometry. PB-DOPA was also generated enzymatically using mushroom tyrosinase, which catalyzes the hydroxylation of tyrosine residues. By comparing the levels of DOPA in radical-damaged or enzyme-treated protein with that of cytochrome c reduction, we show that PB-DOPA is a major source of the observed reducing activity. PB-DOPA may have a role in the replenishment of reduced transition metal ions involved in free radical generating systems in vivo.

Catechols↗
PubMed1993

Free radical and enzymatic mechanisms for the generation of protein bound reducing moieties.

We have previously shown that exposure of many proteins, and free aromatic amino acids (particularly tyrosine) to free radical fluxes generates a stable activity capable of reducing protein bound and free transition metal ions. Here we define the capacity of several radical generating systems (gamma irradiation of water, UV irradiation, metal-dependent sugar autoxidation and Haber-Weiss systems) to produce protein-bound reducing moieties (PBRedM), and also reducing derivatives of tyrosine. Under the defined conditions of the gamma radiolysis system, reductive activity was generated under both oxic and anoxic irradiations and specific gassing regimes as well as the inclusion of specific radical scavengers established that hydroxyl radicals were responsible. When BSA was irradiated anoxically in the presence of formate a reductive activity related to the exposure of protein thiol groups was generated; all other reductive activities we detected were not thiol-related. Incubations of tyrosinase with BSA or insulin also generated reductive activity. All the conditions we have studied can convert tyrosine into DOPA and we suspect that protein-bound DOPA is the main reductive activity generated on proteins.

Amidines↗
PubMed1993

Does superoxide radical have a role in macrophage-mediated oxidative modification of LDL?

Low-density lipoprotein (LDL) oxidation induced by superoxide radicals generated in a cell-free system could not stimulate the subsequent development of high-uptake LDL during incubation in a medium normally permissive for cell-mediated oxidation. Similarly, LDL oxidative modification by macrophages was not accelerated when extracellular superoxide generation was increased 5-10-fold by stimulation of NADPH oxidase. The NADPH oxidase inhibitor, diphenylene iodonium, did inhibit macrophage-mediated modification of LDL, but its effects do not appear to involve superoxide generation. Superoxide dismutase (SOD) was shown to be inappropriate as a test for the involvement of superoxide radicals in cell-mediated oxidation due to its metal-chelating properties and to the development of a pro-oxidant activity by heat inactivation. We conclude that there is presently no secure evidence for the involvement of superoxide radical in macrophage-mediated oxidative modification of LDL.

Animals↗
PubMed1993

Development of a scale measuring genetic variation related to expressive control.

It has been theorized that a substantial genetic component underlies the Self-Monitoring Scale. The identity of this component, however, is not yet known. In order to identify and better understand it, a more precise measure of the component is required. The present research attempted to (a) identify an axis of the self-monitoring two-factor space with maximum genetic variance; and (b) bootstrap a scale more highly correlated with this genetic maximum than is the Self-Monitoring Scale using twins. Evaluation of the new scale against criteria of validity indicates that scale construction was reasonably successful. The new measure had a cross-validated monozygotic twin intraclass correlation of .76 and a dizygotic twin intraclass correlation of .16. This work yields a new research tool and suggests a new approach to personality assessment. Correlates of the new measure as well as theoretical and methodological issues relevant to the measurement of a latent genetic entity are discussed.

Adult↗
PubMed1993

Neutralizing monoclonal antibodies that distinguish three antigenic sites on human cytomegalovirus glycoprotein H have conformationally distinct binding sites.

Seven neutralizing murine monoclonal antibodies specific for the glycoprotein H of human cytomegalovirus were produced and used to construct a topological map of two nonoverlapping antigenic sites that are bridged by a third antigenic site. Neutralization assays with 15 laboratory or clinical human cytomegalovirus strains indicated that the monoclonal antibodies recognize three antigenically variable and three conserved epitopes within the three antigenic sites. The variable-domain genes encoding monoclonal antibodies representing each of the three antigenic sites were cloned and sequenced, and molecular models of their binding sites were generated. Conformational differences in the antibody-binding sites suggested a structural basis for experimentally observed differences in gH epitope recognition.

Amino Acid Sequence↗
PubMed1993

Alginate may accumulate in cystic fibrosis lung because the enzymatic and free radical capacities of phagocytic cells are inadequate for its degradation.

We sought an explanation for the accumulation, and apparent poor degradation by alveolar phagocytes, of alginate in cystic fibrosis lung. A crude intracellular lyase preparation extracted from Klebsiella pneumoniae was able to degrade seaweed alginic acid as well as forms purified from Pseudomonas aeruginosa bacteria from Cystic Fibrosis (CF) patient lungs. This was by a beta-eliminative mechanism, as detected by an increase in the 232nm absorbance and activity was enhanced by deacetylation of the Pseudomonas aeruginosa alginates. Conditioned media or cell lysates from unstimulated or triggered phagocytic cells (including resident mouse peritoneal macrophages and the human macrophage cell line U937) had no effect in the same system. Free radicals generated by chemical systems or by gamma irradiation of water degraded alginate. Depolymerisation by free radicals, as detected by viscosity determinations and polyacrylamide gel electrophoresis, generated a wide range of fragment sizes. In contrast, mouse peritoneal macrophages or human polymorphonuclear neutrophils stimulated to generate free radicals had no significant effect on alginate. Under the conditions of our experiments, phagocytic cells representative of the CF lung are not able to degrade Pseudomonas aeruginosa alginate. This may explain the gross accumulation of alginate in CF lung.

Alginates↗
PubMed1992

Long-lived reactive species on free-radical-damaged proteins.

We have demonstrated two novel reactive species on radical-modified proteins which are relatively long-lived, one oxidizing and one reducing. The two species are reactive with critical biological components, and so may be of physiological and pathological importance. The oxidizing species, which have been identified as protein hydroperoxides, can consume key cellular reductants, such as ascorbate and glutathione. The reducing species can act on both free and metalloprotein forms of copper and iron ions, which participate in radical generation. These findings suggest that proteins may act as traps for the chemical energy released by free radicals, with the capacity to pass it on to other molecules. The long-lived nature of both the reactive moieties indicates that they may be able to diffuse and transfer damaging reactions to distant sites.

Amino Acids↗
PubMed1992

Hypothesis: a damaging role in aging for reactive protein oxidation products?

This paper discusses our knowledge of protein oxidation and its relationship to aging. It also outlines new observations from our laboratories concerning reactive species produced during protein oxidation, and proposes that these may inflict damage on other molecules, and hence contribute to the progression of aging. Whereas it has previously been difficult to see how relatively inert protein oxidation products could possibly have any causal role in aging, the detection of these novel reactive species implies a potentially significant role.

Aging↗
PubMed1992

Differential accuracy in person perception across traits: examination of a functional hypothesis.

Although strangers can assess certain traits of unacquainted others with moderate validity, overall validity is low. Differential validity across traits may be due to (a) the extent to which targets display valid cues or (b) the extent to which perceivers validly use cues. A functionalist perspective suggests that valid cue utilization should vary with how important the consequences of accurate trait assessment are. It was predicted from this perspective that perceivers would judge strangers' sociosexuality more accurately than 3 other traits--social potency, social closeness, and stress reaction. Perceivers viewed 1-min videotaped segments of targets being interviewed and rated them on the 4 traits. Ratings were correlated with target-reported trait measures. As predicted, perceivers' ratings of male sociosexuality agreed relatively well with self-reports. This effect was moderated by sex of target and sex of perceiver.

Adult↗
PubMed1991

Individual differences in sociosexuality: evidence for convergent and discriminant validity.

Individual differences in willingness to engage in uncommitted sexual relations were investigated in 6 studies. In Study 1, a 5-item Sociosexual Orientation Inventory (SOI) was developed. Studies 2, 3, and 4 provided convergent validity evidence for the SOI, revealing that persons who have an unrestricted sociosexual orientation tend to (a) engage in sex at an earlier point in their relationships, (b) engage in sex with more than 1 partner at a time, and (c) be involved in relationships characterized by less investment, commitment, love, and dependency. Study 5 provided discriminant validity for the SOI, revealing that it does not covary appreciably with a good marker of sex drive. Study 6 demonstrated that the SOI correlates negligibly with measures of sexual satisfaction, anxiety, and guilt. The possible stability of, origins of, and motivational bases underlying individual differences in sociosexuality are discussed.

Adult↗
PubMed1991

Preventing falls in hospitals. The roles of patient age and diagnostic status in predicting falls.

Patient falls are some of the most frequent accidents in hospitals, and they can lead to significant personal and financial costs for both patients and facilities. This study examines the relationship between two patients characteristics and patient falls at a large general hospital and a small psychiatric facility in Tennessee; its findings should be useful for hospital risk management.

Accidental Falls↗