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Biomedical subjects

C Anderson

Publications and source records attributed to C Anderson.

At least 55 records · Page 3Linked to original sources

Two-dimensional electrophoresis and mass spectrometric identification of mitochondrial proteins from an SH-SY5Y neuroblastoma cell line.

To probe the mitochondrial involvement in neurodegenerative processes, we have generated a high-resolution map of the mitochondrial proteome from a human neuroblastoma SH-SY5Y cell line that has been used for creating cytoplasmic hybrid cell systems. Two mitochondrial preparations were evaluated using two-dimensional (2D) gel electrophoresis and mass spectrometry; one obtained from differential centrifugation and the other by a multiple-step percoll/metrizamide gradient. The 2D gel maps prepared from these mitochondrial fractions separated over 300 distinct spots as visualized by colloidal Coomassie blue (CCB), or closer to 400 proteins with silver staining. The most abundant proteins identified in the mitochondrial fraction prepared by differential centrifugation were those of mitochondrial, cytoplasmic, and endoplasmic reticulum origin. Proteins obtained using the more intensive two-step gradient method were almost exclusively known to be associated with mitochondria. From this latter preparation, 84 of the most abundant gel spots were analyzed, out of which 61 proteins were identified. The absence of many membrane-associated proteins known to be associated with the mitochondrion and the limited number of total proteins observed in the 2D gel maps suggest that the majority of mitochondrial proteins are not being detected under these separation and staining conditions. An insoluble pellet obtained after solubilization of the mitochondrial fraction prepared with the percoll/metrizamide gradient was boiled in sodium dodecylsulfate (SDS) and separated by 1D sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). This separation yielded some additional proteins, many of which are likely membrane-associated. These studies form the basis for the analysis of differential protein expression in cybrid cellular models of neurodegenerative disorders and in affected tissue from diseased states.

Journal Article↗

Individual versus social complexity, with particular reference to ant colonies.

Insect societies colonies of ants, bees, wasps and termites--vary enormously in their social complexity. Social complexity is a broadly used term that encompasses many individual and colony-level traits and characteristics such as colony size, polymorphism and foraging strategy. A number of earlier studies have considered the relationships among various correlates of social complexity in insect societies; in this review, we build upon those studies by proposing additional correlates and show how all correlates can be integrated in a common explanatory framework. The various correlates are divided among four broad categories (sections). Under 'polyphenism' we consider the differences among individuals, in particular focusing upon 'caste' and specialization of individuals. This is followed by a section on 'totipotency' in which we consider the autonomy and subjugation of individuals. Under this heading we consider various aspects such as intracolony conflict, worker reproductive potential and physiological or morphological restrictions which limit individuals' capacities to perform a range of tasks or functions. A section entitled 'organization of work' considers a variety of aspects, e.g. the ability to tackle group, team or partitioned tasks, foraging strategies and colony reliability and efficiency. A final section, 'communication and functional integration', considers how individual activity is coordinated to produce an integrated and adaptive colony. Within each section we use illustrative examples drawn from the social insect literature (mostly from ants, for which there is the best data) to illustrate concepts or trends and make a number of predictions concerning how a particular trait is expected to correlate with other aspects of social complexity. Within each section we also expand the scope of the arguments to consider these relationships in a much broader sense of'sociality' by drawing parallels with other 'social' entities such as multicellular individuals, which can be understood as 'societies' of cells. The aim is to draw out any parallels and common causal relationships among the correlates. Two themes run through the study. The first is the role of colony size as an important factor affecting social complexity. The second is the complexity of individual workers in relation to the complexity of the colony. Consequently, this is an ideal opportunity to test a previously proposed hypothesis that 'individuals of highly social ant species are less complex than individuals from simple ant species' in light of numerous social correlates. Our findings support this hypothesis. In summary, we conclude that, in general, complex societies are characterized by large colony size, worker polymorphism, strong behavioural specialization and loss of totipotency in its workers, low individual complexity, decentralized colony control and high system redundancy, low individual competence, a high degree of worker cooperation wher tackling tasks, group foraging strategies, high tempo, multi-chambered tailor-made nests, high functional integration, relatively greater use of cues and modulatory signals to coordinate individuals and heterogeneous patterns of worker-worker interaction.

Animals↗

Phototesting based on a divergent beam--a study on normal subjects.

In a previous publication from our group, phototesting based on a single exposure to a divergent UVB beam with radially decreasing irradiance values was suggested. The aim of the present study was to evaluate technical, practical and biological aspects of the suggested method in normal subjects. Twenty healthy volunteers were provoked on the back with both a collimated beam (four fixed doses, in circular areas with a diameter of 1.5 cm) and the divergent beam (a continuous, radially attenuating dose spectrum covering an area with a diameter of 4.5 cm). Eleven of the subjects were subjected to double provocation with the divergent beam. Assessment was carried out at 6 and 24 h after exposure by measuring the diameter of the reactions both visually and by mapping the skin blood flow change with laser Doppler perfusion imaging (LDPI). Minimal erythemal dose (MED) was determined for both the collimated and the divergent provocation. The reaction diameters were used to decide MED by combination to a mm for mm mapped dose spectrum of the divergent beam profile. Dose-response curves were plotted using the quantitative response data of the LDPI-images against the corresponding dosimetry data. No systematic difference could be proven between LDPI and visual diameters and a 95% confidence interval for the mean difference was calculated to (-0.8, 2.0). Slightly greater diameters were found at the visual assessment performed at 6 h compared to 24 h (95% confidence interval (-0.1, 2.8)). Double provocation showed a good reproducibility both for the visual and the LDPI assessment (P<0.05). The divergent beam provocation allowed a more detailed discrimination of MED compared to the collimated beam provocation. The MED values determined with the divergent beam were, however, generally higher, especially in the lower range of MED values. Technical factors related to the beam divergence and the correct measurement of erythemal effective irradiance are believed to be the explanation for this phenomenon, which is thus correctable. In conclusion, the results from this study support our belief that the phototesting protocol based on a divergent beam constitutes a good opportunity for improved phototesting, since MED and dose-response characteristics may be extracted in more detail from a single UV exposure.

Adult↗

Who attains social status? Effects of personality and physical attractiveness in social groups.

One of the most important goals and outcomes of social life is to attain status in the groups to which we belong. Such face-to-face status is defined by the amount of respect, influence, and prominence each member enjoys in the eyes of the others. Three studies investigated personological determinants of status in social groups (fraternity, sorority, and dormitory), relating the Big Five personality traits and physical attractiveness to peer ratings of status. High Extraversion substantially predicted elevated status for both sexes. High Neuroticism, incompatible with male gender norms, predicted lower status in men. None of the other Big Five traits predicted status. These effects were independent of attractiveness, which predicted higher status only in men. Contrary to previous claims, women's status ordering was just as stable as men's but emerged later. Discussion focuses on personological pathways to attaining status and on potential mediators.

Adult↗

Weight loss and gender: an examination of physician attitudes.

OBJECTIVE: The purpose of this study was to investigate physician attitudes toward the treatment of overweight and obese individuals and to evaluate potential gender differences in treatment recommendations. RESEARCH METHODS AND PROCEDURES: A survey describing several hypothetical patients was sent to 700 randomly selected physicians; 209 (29.9%) returned the survey. Two versions of the questionnaire (one for men and one for women) described three hypothetical patients at three levels of body mass index (BMI) (32, 28, and 25 kg/m(2)). One-half of the physicians received a version of the questionnaire describing the patients as women, and one-half received a version describing the patients as men. Respondents answered questions about attitudes toward treatment and specific interventions and referrals they would view as appropriate. RESULTS: Physicians were more likely to encourage women with a BMI of 25 kg/m(2) to lose weight than men with the same BMI, and indicated that they would suggest more treatment referrals for women than men. Men with a BMI of 32 kg/m(2) were more likely to be encouraged to lose weight than women with the identical BMI. Physicians were more likely to encourage weight loss and see treatment referrals as appropriate for patients with higher BMIS: DISCUSSION: This study indicates that physicians treat male and female patients differently, with physicians more likely to encourage weight loss and provide referrals for women with a BMI of 25 kg/m(2) than for men with an identical BMI and less likely to encourage weight loss for women than men with a BMI of 32 kg/m(2).

Adult↗

Incidence of cleft palate fistula: an institutional experience with two-stage palatal repair.

The purpose of this study was to determine the incidence of cleft palatal fistula in a series of nonsyndromic children treated at the authors' institution. This retrospective analysis of 103 patients with cleft palate treated by five surgeons between 1982 and 1995 includes 60 boys and 33 girls, whose median age was 18.4 months at the time of surgery. The median length of follow-up was 4.9 years after primary palatoplasty. Cleft palatal fistula was defined as a failure of healing or a breakdown in the primary surgical repair of the palate. Intentionally unrepaired fistulas of the primary and secondary palate were excluded. Extent of clefting was described according to the Veau classification. Statistical examination of multiple variables was performed using contingency table analysis, multivariate logistic regression, and the Wilcoxon rank sum test. The incidence of cleft palatal fistula in this series was 8.7 percent. All of these fistulas were clinically significant. The rate of fistula recurrence was 33 percent. The incidence of cleft palatal fistula when compared by Veau classification was statistically significant, with nine fistulas occurring in patients with Veau 3 and 4 clefts and no fistulas occurring in patients with Veau 1 and 2 clefts (p = 0.0441). No significant differences between patients with and without fistulas were identified with respect to operating surgeon, patient sex, patient age at palatoplasty, type of palatoplasty, and use of presurgical orthopedics or palatal expansion. All three recurrent fistulas occurred in the anterior palate, two in patients with Veau class 3 clefts and one in a patient with a Veau class 4 cleft. The low rate of clinically significant fistula was attributed to early delayed primary closure, with smaller secondary clefts allowing repair with a minimum of dissection and disruption of vascularity.

Cleft Palate↗

Slow induction of RecA by DNA damage in Mycobacterium tuberculosis.

In mycobacteria, as in most bacterial species, the expression of RecA is induced by DNA damage. However, the authors show here that the kinetics of recA induction in Mycobacterium smegmatis and in Mycobacterium tuberculosis are quite different: whilst maximum expression in M. smegmatis occurred 3-6 h after addition of a DNA-damaging agent, incubation for 18-36 h was required to reach peak levels in M. tuberculosis. This is despite the fact that the M. tuberculosis promoter can be activated more rapidly when transferred to M. smegmatis. In addition, it is demonstrated that in both species the DNA is sufficiently damaged to give maximum induction within the first hour of incubation with mitomycin C. The difference in the induction kinetics of recA between the two species was mirrored by a difference in the levels of DNA-binding-competent LexA following DNA damage. A decrease in the ability of LexA to bind to the SOS box was readily detected by 2 h in M. smegmatis, whilst a decrease was not apparent until 18-24 h in M. tuberculosis and then only a very small decrease was observed.

Alkylating Agents↗

Hyperactive glycogen synthase mutants of Saccharomyces cerevisiae suppress the glc7-1 protein phosphatase mutant.

A yeast glc7-1 mutant expressing a variant of protein phosphatase type 1 fails to accumulate glycogen. This defect is associated with hyperphosphorylated and inactive glycogen synthase, consistent with Glc7p acting directly to dephosphorylate and activate glycogen synthase. To characterize the glycogen synthesis defect of this mutant in more detail, we isolated 26 pseudorevertants of the glc7-1 mutant. All pseudoreversion events were due to missense mutations in GSY2, the gene encoding the major isoform of glycogen synthase. A majority of the mutations responsible for the suppression were in the 3' end of the gene, corresponding to the phosphorylated COOH terminus of Gsy2p. Phosphorylation of the mutant proteins was reduced, suggesting that they are poor substrates for glycogen synthase kinases. Suppressor mutations outside this domain did not decrease the phosphorylation of the resulting proteins, indicating that these proteins are immune to the regulatory effects of phosphorylation. Since no growth defect has been observed for strains with altered glycogen levels, the relative levels of fitness of GSY2 mutants that fail to accumulate glycogen and that hyperaccumulate glycogen were assayed by cocultivation experiments. A wild-type strain outcompeted both hypo- and hyperaccumulating strains, suggesting that glycogen levels contribute substantially to the fitness of yeast.

Amino Acid Sequence↗

Zygotic regulation of maternal cyclin A1 and B2 mRNAs.

At the midblastula transition, the Xenopus laevis embryonic cell cycle is remodeled from rapid alternations between S and M phases to become the complex adult cell cycle. Cell cycle remodeling occurs after zygotic transcription initiates and is accompanied by terminal downregulation of maternal cyclins A1 and B2. We report here that the disappearance of both cyclin A1 and B2 proteins is preceded by the rapid deadenylation of their mRNAs. A specific mechanism triggers this deadenylation. This mechanism depends upon discrete regions of the 3' untranslated regions and requires zygotic transcription. Together, these results strongly suggest that zygote-dependent deadenylation of cyclin A1 and cyclin B2 mRNAs is responsible for the downregulation of these proteins. These studies also raise the possibility that zygotic control of maternal cyclins plays a role in establishing the adult cell cycle.

3' Untranslated Regions↗

Hormonal factors and risk of aneurysmal subarachnoid hemorrhage: an international population-based, case-control study.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is more common in women than in men, but the role of hormonal factors in its etiology remains uncertain. The aim of this study was to examine the relationship between hormonal factors and risk of SAH in women. METHODS: This was a prospective, multicenter, population-based, case-control study performed in 4 major urban centers in Australia and New Zealand. Two hundred sixty-eight female cases of first-ever aneurysmal SAH occurred during 1995-1998. Controls were 286 frequency-matched women from the general population of each center. Outcome measures included risk of SAH associated with use of oral contraceptive pills (OCPs), hormone replacement therapy (HRT), and various endogenous hormonal factors including menstrual patterns, parity, age at birth of first child, and breast-feeding practices. RESULTS: Cases and controls did not differ with regard to menstrual and reproductive history except in age at birth of first child, where older age was associated with reduced risk of SAH (odds ratio [OR], 0.63; 95% CI, 0.43, 0.91). Relative to never use of HRT, the adjusted OR for ever use of HRT was 0.64 (95% CI, 0.41, 0.98), which did not alter significantly after further adjustment for possible confounding factors. Borderline evidence of an inverse association was detected for past use of HRT (adjusted OR, 0.59; 95% CI, 0.30, 1.13) and current use of HRT (adjusted OR, 0.67; 95% CI, 0.40, 1.13), but there was no evidence of an association for use of OCPs (adjusted OR, 0.97; 95% CI, 0.58, 1.60). CONCLUSIONS: The risks of SAH are lower in women whose first pregnancy is at an older age and women who have ever used HRT but not OCPs. The findings suggest an independent etiologic role for hormonal factors in the pathogenesis of aneurysmal SAH and provide support for a protective role for HRT on risk of SAH in postmenopausal women.

Age Distribution↗

Systemic adverse effects of ophthalmic beta-blockers.

OBJECTIVE: To review published clinical information on the systemic adverse effects of ophthalmic beta-blockers for the purpose of developing a pilot contraindication/warning system for active prescriptions in the Veterans Affairs dispensing database. DATA SOURCES: Articles were identified by searching MEDLINE (1966-October 2000) and International Pharmaceutical Abstracts (1970-October 2000). STUDY SELECTION AND DATA EXTRACTION: Article relevance was determined by review of titles, abstracts, and key words. DATA SYNTHESIS: The preponderance of the evidence suggests that ophthalmic beta-blockers may be associated with bronchospasm and adverse cardiovascular effects including bradycardia. Depression and other central nervous system effects are reported less commonly. Data are inadequate to suggest that ophthalmic beta-blocker use is routinely associated with adverse metabolic effects. CONCLUSIONS: The strongest level of evidence (grade A1) supports a contraindication for use of ophthalmic beta-blockers for respiratory disease, with a moderate level of evidence (grade B1) for cardiovascular disease. Data are insufficient to support or refute contraindications for other disease states. The search technique and classification scheme described in this article provide a methodology for evaluating, grading, and applying evidence on potential adverse effects of drug therapy.

Adrenergic beta-Antagonists↗

Rates of pediatric and adolescent injuries by year of age.

OBJECTIVE: The purpose of this study was to analyze causes of injury hospitalization/death by individual year of age and by specific causes of injury and to examine how well aggregate age groups represented individual year-of-age rates. METHODS: Hospital discharge data and death certificate data for California residents age 0 to 19 years with a principal external cause of injury code (E-code) of E800 to E869, E880 to E929, or E950 to E999, calendar year 1997, were analyzed. Annual rates of injury hospitalization/death by year of age were calculated using combined hospital discharges and deaths as the numerator for major causes and important subcategories. For comparison, rates of injury hospitalization/death were calculated for conventional vital statistics age groups: <1 year, 1 to 4 years; 5 to 9 years, 10 to 14 years, and 15 to 19 years. RESULTS: In 1997 in California, 35 277 children and adolescents 0 to 19 years were hospitalized and 1934 died as a result of injury, a ratio of 17 hospitalizations to 1 death. The distribution was bimodal with rates highest among 18-year-olds (732/100 000) and 1-year-olds (495/100 000). Except for children who were 5 to 9 years of age, the group rates for all injuries were not reflective of the individual year-of-age rates. In specific categories of injuries, variation in rates by year of age were masked by age group rates for unintentional poisoning among 1- to 4-year-olds, self-inflicted poisoning for 10- to 19-year-olds, falls from playground equipment among 5- to 9-year-olds, falls from furniture among 1- to 4-year-olds, and motor vehicle occupant injury rates among 10- to 19-year-olds. The peak rate of falls from playground equipment among 6-year-olds (34/100 000) was more than twice the rate for 9-year-olds (15/1000,000). Motor vehicle occupant injury rates doubled between 10 and 14 years of age and quadrupled between 14 and 18 years of age. CONCLUSIONS: Analyses using conventional age groups did not identify the age of highest risk for many causes of childhood injury. Changes in the rates often transected the traditional age groups and were not apparent with conventional age group analysis. These data can inform on the age at which to begin a specific injury intervention and on how to allocate resources. These data allow pediatricians and other health professionals to be anticipatory in providing injury prevention counseling. The greatest impact can be achieved by making the counseling topic most age appropriate in anticipation of the high-risk period.

Accidental Falls↗

Reviewing the review process: examining decision-making in practice.

A national multi-disciplinary audit showed variation in SLT practice on the decision to review pre-school children or place them on waiting lists following initial assessment. Audit evidence suggests some reasons for these differences and contributing factors are illustrated by case history examples. Current health-care policies encourage practitioners to make decision-making transparent to consumers but this process is problematic if there is a lack of evidence to support principled choice. An outline is presented to enable therapists to gather their own evidence for review outcomes in daily practice.

Child, Preschool↗

HIV protease as a target for retrovirus vector-mediated gene therapy.

The dimeric aspartyl protease of HIV has been the subject of intense research for almost a decade. Knowledge of the substrate specificity and catalytic mechanism of this enzyme initially guided the development of several potent peptidomimetic small molecule inhibitors. More recently, the solution of the HIV protease structure led to the structure-based design of improved peptidomimetic and non-peptidomimetic antiviral compounds. Despite the qualified success of these inhibitors, the high mutation rate associated with RNA viruses continues to hamper the long-term clinical efficacy of HIV protease inhibitors. The dimeric nature of the viral protease has been conducive to the investigation of dominant-negative inhibitors of the enzyme. Some of these inhibitors are defective protease monomers that interact with functional monomers to form inactive protease heterodimers. An advantage of macromolecular inhibitors as compared to small-molecule inhibitors is the increased surface area of interaction between the inhibitor and the target gene product. Point mutations that preserve enzyme activity but confer resistance to small-molecule inhibitors are less likely to have an adverse effect on macromolecular interactions. The use of efficient retrovirus vectors has facilitated the delivery of these macromolecular inhibitors to primary human lymphocytes. The vector-transduced cells were less susceptible to HIV infection in vitro, and showed similar levels of protection compared to other macromolecular inhibitors of HIV replication, such as RevM10. These preliminary results encourage the further development of dominant-negative HIV protease inhibitors as a gene therapy-based antiviral strategy.

Amino Acid Sequence↗

Evaluation of massage with essential oils on childhood atopic eczema.

Childhood atopic eczema is an increasingly common condition in young children. As well as being irritating to the child, it causes sleepless nights for both the child and the family and leads to difficulties in parental relationships and can have severe effects on employment. A group of eight children, born to professional working mothers were studied to test the hypothesis that massage with essential oils (aromatherapy) used as a complementary therapy in conjunction with normal medical treatment, would help to alleviate the symptoms of childhood atopic eczema. The children were randomly allocated to the massage with essential oils group and both counselled and massaged with a mixture of essential oils by the therapist once a week and the mother every day over a period of 8 weeks. The preferred essential oils, chosen by the mothers for their child, from 36 commonly used aromatherapy oils, were: sweet marjoram, frankinsence, German chamomile, myrrh, thyme, benzoin, spike lavender and Litsea cubeba. A control group of children received the counselling and massage without essential oils. The treatments were evaluated by means of daily day-time irritation scores and night time disturbance scores, determined by the mother before and during the treatment, both over an 8 week period; finally general improvement scores were allocated 2 weeks after the treatment by the therapist, the general practitioner and the mother. The study employed a single case experimental design across subjects, such that there were both a within-subject control and between-subjects control, through the interventions being introduced at different times. The results showed a significant improvement in the eczema in the two groups of children following therapy, but there was no significant difference in improvement shown between the aromatherapy massage and massage only group. Thus there is evidence that tactile contact between mother and child benefits the symptoms of atopic eczema but there is no proof that adding essential oils is more beneficial than massage alone. Further studies on the essential oil massage group showed a deterioration in the eczematous condition after two further 8 week periods of therapy, following a period of rest after the initial period of contact. This may have been due to a decline in the novelty of the treatment, or, it strongly suggests possible allergic contact dermatitis provoked by the essential oils themselves. The results of this study indicate the necessity of prolonged studies with novel plant extracts as short-term beneficial results could be overturned by adverse effects after repeated usage.

Aromatherapy↗

Health promotion in community pharmacy: the UK situation.

Community pharmacies in the UK are an excellent setting for health promotion in the community; they see over 90% of the population per year. Pharmacy education and training is changing and health promotion is now part of the undergraduate curriculum. There is an increasing body of research about the effects of pharmacy health promotion and a number of examples of good practice. The UK research is reviewed and examples of good practice highlighted. The paper concludes with a discussion about the contribution of pharmacists can make and about some of the issues that will need to be overcome first. Pharmacists see healthy as well as sick people. They have a special relationship with many of their regular customers which enables them to promote health, they can also give population messages to passing trade. A number of issues such as training and remuneration must be addressed before health promotion becomes fully integrated into the pharmacist's role.

Community Health Services↗