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Biomedical subjects

A Young

Publications and source records attributed to A Young.

At least 91 records · Page 5Linked to original sources
PubMed2000

Cytoplasmic dynein-mediated assembly of pericentrin and gamma tubulin onto centrosomes.

Centrosome assembly is important for mitotic spindle formation and if defective may contribute to genomic instability in cancer. Here we show that in somatic cells centrosome assembly of two proteins involved in microtubule nucleation, pericentrin and gamma tubulin, is inhibited in the absence of microtubules. A more potent inhibitory effect on centrosome assembly of these proteins is observed after specific disruption of the microtubule motor cytoplasmic dynein by microinjection of dynein antibodies or by overexpression of the dynamitin subunit of the dynein binding complex dynactin. Consistent with these observations is the ability of pericentrin to cosediment with taxol-stabilized microtubules in a dynein- and dynactin-dependent manner. Centrosomes in cells with reduced levels of pericentrin and gamma tubulin have a diminished capacity to nucleate microtubules. In living cells expressing a green fluorescent protein-pericentrin fusion protein, green fluorescent protein particles containing endogenous pericentrin and gamma tubulin move along microtubules at speeds of dynein and dock at centrosomes. In Xenopus extracts where gamma tubulin assembly onto centrioles can occur without microtubules, we find that assembly is enhanced in the presence of microtubules and inhibited by dynein antibodies. From these studies we conclude that pericentrin and gamma tubulin are novel dynein cargoes that can be transported to centrosomes on microtubules and whose assembly contributes to microtubule nucleation.

Animals↗
PubMed2000

Changes in the expression of nitric oxide synthase in the human uterine cervix during pregnancy and parturition.

Nitric oxide (NO) has been proposed as a mediator of cervical ripening. We investigated the expression, using Western blotting, and localization, using immunohistochemistry, of the nitric oxide synthase (NOS) enzymes, inducible NOS (iNOS), endothelial NOS (eNOS) and neuronal NOS (bNOS) in the human cervix during pregnancy and parturition. Cervical biopsies were obtained from non-pregnant women, women in the first trimester of pregnancy, and pregnant women at term before and after the onset of labour. Each of the NOS isoforms was localized in the cervices of both non-pregnant and pregnant subjects using immunohistochemistry. iNOS expression was significantly greater in early pregnancy compared with the non-pregnant state (P: < 0.005). iNOS expression was up-regulated further in samples obtained in the third trimester compared with the first trimester. bNOS expression was greater in samples from the first trimester of pregnancy than in non-pregnant samples (P: < 0. 005), but showed no additional increase in late pregnancy or with the onset of labour. eNOS expression was increased in samples obtained in the third trimester both before (P: = 0.002) and after the onset of labour (P: < 0.002) when compared with non-pregnant samples. The increased expression of NOS isoforms in late pregnancy supports the hypothesis that NO is involved in the process of cervical ripening.

Blotting, Western↗
PubMed2000

How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)

OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives. METHODS: The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease-modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work. RESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0). CONCLUSIONS: Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.

Adult↗
PubMed2000

Reexamination of the effect of endotoxin on cell proliferation and transfection efficiency.

Plasmid DNA purified from bacterial cells can be contaminated with endotoxin to different extents, depending on the purification method. Earlier reports indicate that endotoxin can decrease transfection efficiency in many eukaryotic cell lines; however, the amount of endotoxin required for inhibition is unclear. We determined endotoxin effects in several cell lines and observed that endotoxin levels greater than or equal to 10,000 endotoxin units (EU) were needed to significantly affect cell proliferation and viability; levels greater than 2000 EU/mu g DNA were required to significantly inhibit transfection for all but one (Huh-7) of the cell lines tested. These endotoxin levels are significantly higher than endotoxin contamination in plasmid DNA purified by anion exchange, CsCl2 gradient and endotoxin-free purification technology, but not as high as a crude alkaline lysis preparatory method. Plasmid DNA prepared using anion exchange technology was comparable to endotoxin-free technology in terms of transfection efficiency. Even Huh-7 cells, which are markedly more sensitive to endotoxins, have comparable transfection efficiencies using plasmid DNA purified by either of these two methods. We conclude that for those cell lines commonly used for transfection studies, endotoxin-free, quality DNA is not necessary because significantly higher levels of bacterial endotoxins are required to inhibit either cell proliferation or transfection.

Animals↗
PubMed2000

Creutzfeldt-Jakob disease guidelines: a regional approach.

Creutzfeldt-Jakob Disease (CJD) is an infectious, progressive, degenerative neurological disorder. Unique CJD Precautions must be adhered to as the infectious agent is difficult to destroy. A regional group in Hamilton-Burlington Ontario developed CJD guidelines based on critical review of the current evidence of transmission in a Canadian healthcare environment, current published standards of practice in North America, the United Kingdom and Australia; and principles of laboratory and patient care safety as well as expert opinion.

Creutzfeldt-Jakob Syndrome↗
PubMed1999

W. H. R. Rivers and the war neuroses.

W. H. R. Rivers was the most famous member of the Cambridge Expedition to the Torres Strait. At the time, he was a physician and had an international reputation as a researcher in physiological psychology. The expedition signaled the beginning of his career in social anthropology, but also a long hiatus in his activities in medicine. His clinical interests revived during World War I. As an officer in the Royal Army Medical Corps (RAMC), Rivers became a leading proponent of "psychological medicine." Today, his war-time psychiatry is remembered mainly in association with his patient, Siegfried Sassoon. This article focuses on his wartime activities, his clinical practices, and his theories concerning the war neuroses and the unconscious. The currently popular view of Rivers as a quasi-Freudian humanist is challenged.

Combat Disorders↗
PubMed1999

Team leadership: network differences in women's and men's instrumental and expressive relations.

Recent studies have emphasised differences in leadership styles between women and men. Women have an "interactive" leadership style while men are more "directive" and "authoritative." Social network analysis is used to examine differences in eight mental health case management teams, half formally supervised by women and half by men. The techniques used are graphical displays and measures of centrality. Results show male leaders as the most central team member for both instrumental and expressive relations. Female leaders, however, do not adhere to a single leadership style. Team centralisation also differs with gender composition of teams influencing leadership differences.

Adult↗
PubMed1999

Culture and context in the evolutionary concept of mental disorder.

The evolutionary theory of the concept of mental disorder as harmful dysfunction that J. C. Wakefield (1999) proposed (a) does not correspond to how the term disorder is used in psychiatric nosology or in clinicians' everyday practice; (b) does not cover the territory to which the term reasonably could be applied; and (c) is not especially useful for research, clinical, or social purposes. The broad concept of disorder is a polythetic, not a monothetic, concept. As such, there need be no essential characteristic, criterion, or single prototype of disorder. Instead, multiple prototypes with varying features are used to group together a wide range of disparate phenomena by analogy. Useful refinements of our concepts of disorder have come from analyses of the nature of action and intentionality. What are most needed now are careful analyses of the social embedding of our concepts in cultural knowledge and practice.

Biological Evolution↗
PubMed1999

Fourteen-year follow-up of children with and without speech/language impairments: speech/language stability and outcomes.

This report concerns the speech and language outcomes of young adults (N = 242) who participated in a 14-year, prospective, longitudinal study of a community sample of children with (n = 114) and without (n = 128) speech and/or language impairments. Participants were initially identified at age 5 and subsequently followed at ages 12 and 19. Direct assessments were conducted in multiple domains (communicative, cognitive, academic, behavioral, and psychiatric) at all three time periods. Major findings included (a) high rates of continued communication difficulties in those with a history of impairment; (b) considerable stability in language performance over time; (c) better long-term outcomes for those with initial speech impairments than for those with language impairments; and (d) more favorable prognoses for those with specific language impairments than for those with impairments secondary to sensory, structural, neurological, or cognitive deficits. These general conclusions held when either a liberal or a more stringent criterion for language impairment was employed. Some of these findings are consistent with those from earlier follow-up studies, which used less optimal methods. Thus, the present replication and extension of these findings with a sound methodology enables greater confidence in their use for prognostic, planning, and research purposes.

Adolescent↗
PubMed1999

A patient preference study comparing raltitrexed ('Tomudex') and bolus or infusional 5-fluorouracil regimens in advanced colorectal cancer: influence of side-effects and administration attributes.

Current chemotherapy regimens used in advanced colorectal cancer (ACRC) are similar in terms of efficacy, but differ importantly in terms of side-effects and administration profiles. These differences may impact significantly on patients' lives. We have evaluated patient preferences between raltitrexed ('Tomudex') and 5-fluorouracil-based chemotherapy regimens, with regard to side-effect attributes (raltitrexed and Mayo regimens) and administration attributes (raltitrexed, Mayo, De Gramont and Lokich regimens) in a study based on 82 patients with ACRC. Patients completed a series of rating tasks on how 'upsetting' these attributes were to them using a visual analogue scale (VAS) in a structured interview conducted by a research nurse. Mucositis and asthenia were the most and least upsetting side-effects, respectively. The side-effect profile of raltitrexed was clearly preferred by 78% of patients versus 14% for Mayo (P < 0.001). When side-effects and administration attributes were combined into an overall profile, 91% of patients selected raltitrexed as their clearly preferred regimen, versus 6% for Mayo (P < 0.001). The administration regimen of raltitrexed was ranked most acceptable (mean rank score 1.5 compared with Mayo 2.6, De Gramont 2.7, and Lokich 3.3). Given similar palliative effects, patients with ACRC exhibit preferences for raltitrexed over other regimens, based on administration and/or side-effect attributes. Such preferences should constitute an important part of decisions relating to the choice of chemotherapy regimen in ACRC.

Adult↗
PubMed1999

Quantitative and qualitative analyses of human salivary micelle-like globules.

In the present study we examined the protein proportion and amino acid profile of the salivary micelle-like globules (SMGs) of human whole saliva and parotid saliva (HWS, HPS). Saliva and SMG samples from each subject (clarified HWS and HPS from 6 subjects, and unclarified HWS from 3 subjects) were analysed for amino acids using standard acid hydrolysis procedures. HPS, clarified HWS and the respective supernatant samples (remaining after removal of the SMGs) were also measured for protein using the micro-Kjeldahl method. SMGs from clarified and unclarified HWS made up 4.7% and 19.7%, respectively, of the total salivary protein based on amino acid analyses. With the micro-Kjeldahl method SMGs from clarified HWS made up 7.3% of the total saliva protein. SMGs isolated from HPS were found in only small amounts. The amino acid profile for the SMGs was strikingly similar to that known for the 2-h pellicle, and differed significantly from HWS or HPS. The results support previous morphological studies indicating that the SMGs represent a major component of the newly formed pellicle.

Adult↗
PubMed1999

Effects of four herbal extracts on adjuvant-induced inflammation and hyperalgesia in rats.

OBJECTIVE: To evaluate the effects of four herbal medicine extracts on a rat model of inflammatory hyperalgesia. DESIGN/INTERVENTIONS: Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hindpaw of each rat. Four herbs that are routinely prescribed in Traditional Chinese Medicine for treatment of pain were used: Duhuo (Radix Angelicae Pubescentis), Bai jiang cao (Patriniae Herba cum Radice), Yan hu suo (Rhizoma Corydalis) and Sanqui (Panax Notoginseng). The crude water extracts of the herbs were inected intraperitoneally following a repeated treatment profile. OUTCOME MEASURES: Thermal hyperalgesia was assessed by testing each rat's paw withdrawal response to a noxious thermal stimulus. The magnitude of edema was determined by measuring the maximal thickness of the paw with a caliper. The effect of herb extracts on motor performance was assessed by using an accelerating rotarod test. RESULT: Duhuo, Bai jiang cao, and Yan hu suo significantly attenuated CFA-induced hyperalgesia at 2 hours and facilitated the recovery from hyperalgesia (p < 0.05), when compared to saline-treated rats. The CFA-induced edema was reduced by Duhuo at 24 hours, 72 hours and 168 hours; Bai jiang cao at 24 hours, and Yan hu suo at 24 hours and 168 hours. Sanqi did not produce any significant effect on inflammation and hyperalgesia. The rotarod performance was slightly reduced by Bai jiang cao, Yan hu suo, and Sanqi (p < 0.05) but not by Duhuo treatment. CONCLUSION: The present study identified Duhuo as a selective and effective herbal agent in attenuating persistent hindpaw inflammation and hyperalgesia in rats. These results indicate that some herbal agents may provide an alternative approach to the treatment of persistant inflammatory pain and hyperalgesia.

Animals↗