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Biomedical subjects

R Watson

Publications and source records attributed to R Watson.

At least 37 records · Page 2Linked to original sources

Aerobic capacities in the skeletal muscles of Weddell seals: key to longer dive durations?

In contrast to terrestrial animals that function under hypoxic conditions but display the typical exercise response of increasing ventilation and cardiac output, marine mammals exercise under a different form of hypoxic stress. They function for the duration of a dive under progressive asphyxia, which is the combination of increasing hypoxia, hypercapnia and acidosis. Our previous studies on short-duration, shallow divers found marked adaptations in their skeletal muscles, which culminated in enhanced aerobic capacities that are similar to those of athletic terrestrial mammals. The purpose of the present study was to assess the aerobic capacity of skeletal muscles from long-duration divers. Swimming and non-swimming muscles were collected from adult Weddell seals, Leptonychotes weddelli, and processed for morphometric analysis, enzymology, myoglobin concentrations and fiber-type distribution. The results showed that the skeletal muscles of Weddell seals do not have enhanced aerobic capacities compared with those of terrestrial mammals but are adapted to maintain low levels of an aerobic lipid-based metabolism, especially under the hypoxic conditions associated with diving. The lower aerobic capacity of Weddell seal muscle as compared with that of shorter-duration divers appears to reflect their energy-conserving modes of locomotion, which enable longer and deeper dives.

3-Hydroxyacyl CoA Dehydrogenases↗

Systematic distortions in world fisheries catch trends.

Over 75% of the world marine fisheries catch (over 80 million tonnes per year) is sold on international markets, in contrast to other food commodities (such as rice). At present, only one institution, the Food and Agriculture Organization of the United Nations (FAO) maintains global fisheries statistics. As an intergovernmental organization, however, FAO must generally rely on the statistics provided by member countries, even if it is doubtful that these correspond to reality. Here we show that misreporting by countries with large fisheries, combined with the large and widely fluctuating catch of species such as the Peruvian anchoveta, can cause globally spurious trends. Such trends influence unwise investment decisions by firms in the fishing sector and by banks, and prevent the effective management of international fisheries.

Agriculture↗

Eradication of colorectal xenografts by combined radioimmunotherapy and combretastatin a-4 3-O-phosphate.

Solid tumors have a heterogeneous pathophysiology, which has a major impact on therapy. Using SW1222 colorectal xenografts grown in nude mice, we have shown that antibody-targeted radioimmunotherapy (RIT) effectively treated the well-perfused tumor rim, producing regressions for approximately 35 days, but was less effective at the more hypoxic center. By 72 h after RIT, the number of apoptotic cells rose from an overall value of 1% in untreated tumors to 35% at the tumor periphery and 10% at the center. The antivascular agent disodium combretastatin A-4 3-O-phosphate (CA4-P) rapidly reduced tumor blood flow to 62% of control values by 1 h, 23% by 3 h, and between 32-36% from 6 to 24 h after administration. This created central hemorrhagic necrosis, but a peripheral rim of cells continued to grow, and survival was unaffected. Changes in the pattern of perfusion across the tumor over time were zonal. Untreated mice showed perfusion throughout the tumor, with greatest activity at the rim. There was an overall reduction at 1 h, and total cessation of central perfusion from 3 h onward. A narrow peripheral rim of perfusion was always present, which increased in intensity and extent between 6 and 24 h, either through reperfusion or new vessel growth. Combining these two complementary therapies (7.4 MBq (131)I-labeled anti-carcinoembryonic antigen IgG i.v. plus a single 200 mg/kg dose of CA4-P i.p.) produced complete cures in five of six mice for >9 months. Allowing maximal tumor localization of antibody (48 h) before blood flow inhibition by CA4-P increased tumor retention by two to three times control levels by 96 h without altering normal tissue levels, as confirmed by gamma counting and phosphor image analysis. The success of this combined, synergistic therapy was probably the result of several factors: (a) the killing of tumor cells in the outer, radiosensitive region by targeted radiotherapy; (b) enhancement of RIT by entrapment of additional radioantibody after combretastatin-induced vessel collapse; and (c) destruction of the central, more hypoxic and radioresistant region by CA4-P. This work demonstrates the need to consider cancer treatment in a biologically heterogeneous setting, if results are to be effectively translated to the clinic.

Adenocarcinoma↗

Cyclin A1 directly interacts with B-myb and cyclin A1/cdk2 phosphorylate B-myb at functionally important serine and threonine residues: tissue-specific regulation of B-myb function.

Cyclin A1 is tissue-specifically expressed during spermatogenesis, but it is also highly expressed in acute myeloid leukemia (AML). Its pathogenetic role in AML and in the cell cycle of leukemic blasts is unknown. B-myb is essential for G1/S transition and has been shown to be phosphorylated by the cyclin A2/cdk2 complex. Here it is demonstrated that cyclin A1 interacts with the C-terminal portion of B-myb as shown by glutathione S-transferase (GST) precipitation. This interaction is confined to cyclin A1 because binding could not be detected between cyclin A2 and B-myb. Also, cdk2 was not pulled down by GST-B-myb from U937 lysates. In addition, co-immunoprecipitation of cyclin A1 and B-myb in leukemic cells evidenced protein interaction in vivo. Baculovirus-expressed cyclin A1/cdk2 complexes were able to phosphorylate human as well as murine B-myb in vitro. Tryptic phosphopeptide mapping revealed that cyclin A1/cdk2 complexes phosphorylated the C-terminal part of B-myb at several sites including threonine 447, 490, and 497 and serine 581. These phosphorylation sites have been demonstrated to be important for the enhancement of B-myb transcriptional activity. Further studies showed that cyclin A1 cooperated with B-myb to transactivate myb binding site containing promoters including the promoter of the human cyclin A1 gene. Taken together, the data suggest that cyclin A1 is a tissue-specific regulator of B-myb function and activates B-myb in leukemic blasts. (Blood. 2001;97:2091-2097)

Animals↗

A 35-item version of the Caring Dimensions Inventory (CDI-35): multivariate analysis and application to a longitudinal study involving student nurses.

The present study was designed to investigate the perceptions of caring among student nurses and how these develop throughout the course of a programme of pre-registration nurse education. A 35-item version of the caring dimensions inventory was administered to a cohort of nursing students in a department of nursing in Scotland at entry to the programme, after 12 months and after 24 months on the programme. Caring was largely perceived through a technical dimension, demonstrated by factor analysis, but other dimensions such as intimacy, support and unnecessary and inappropriate aspects of nursing also became apparent as students progressed through the programme.

Adult↗