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P J Duke

Publications and source records attributed to P J Duke.

36 records · Page 2Linked to original sources

In vivo and in vitro studies of cartilage differentiation in altered gravities.

The in vivo model our laboratory uses for studies of cartilage differentiation in space is the rat growth plate. Differences between missions, and in rat age and recovery times, provided differing results from each mission. However, in all missions, proliferation and differentiation of chondrocytes in the epiphyseal plate of spaceflown rats was altered as was matrix organization. In vitro systems, necessary complements to in vivo work, provide some advantages over the in vivo situation. In vitro, centrifugation of embryonic limb buds suppressed morphogenesis due to precocious differentiation, and changes in the developmental pattern suggest the involvement of Hox genes. In space, embryonic mouse limb mesenchyme cells differentiating in vitro on IML-1 had smoother membranes and lacked matrix seen in controls. Unusual formations, possibly highly ruffled membranes, were found in flight cultures. These results, coupled with in vivo centrifugation studies, show that in vivo or in vitro, the response of chondrocytes to gravitational changes follows Hert's curve as modified by Simon, i.e. decreased loading decreases differentiation, and increased loading speeds it up, but only to a point. After that, additional increases again slow down chondrogenesis.

Animals↗

Psychopathology, social and cognitive functioning in a hostel for homeless women.

BACKGROUND: This study surveyed all residents in a hostel for homeless women. Demographic data, and information on past and present psychiatric and social morbidity, and current and premorbid cognitive functioning were collected. METHOD: A four week prevalence study, using: SCID-PD; a semi-structured interview; GHQ; SBS; Manchester Scale; MMSE; and NART; the data were analysed using SPSS. RESULTS: The women originated from across the social spectrum and disruption of early family life was common. Fifty per cent had a 'severe mental illness' and most were not receiving drug treatment. High levels of active psychotic symptoms were present. Women with psychosis had suffered a greater intellectual decline from their premorbid levels of functioning than those without psychosis. CONCLUSIONS: The study affirmed findings of earlier studies employing case-studies methodology. Women with high levels of psychiatric morbidity and social dysfunction were being managed by care workers in a way that may promote stability rather than a drift into street-life.

Adolescent↗

Cognitive function and duration of rooflessness in entrants to a hostel for homeless men.

BACKGROUND: Four previous studies of homeless adults have yielded conflicting results regarding the presence of cognitive impairment. METHOD: A consecutive series of 80 roofless entrants to a hostel for homeless men were sampled and 62 (76%) completed a range of assessments, including measures of mental state, cognitive functions and substance use. RESULTS: Estimated premorbid IQ (mean = 96), current IQ (mean = 84) and cognitive speed were significantly lower than the norm. There was a significant IQ drop in all diagnostic groups. IQ drop, but not current IQ, correlated with duration of rooflessness. Those with schizophrenia or alcohol problems were roofless for longest. Alcohol misuse did not correlate with IQ drop, excepting alcohol withdrawal symptoms in those with schizophrenia. CONCLUSION: The hypothesis that low IQ is a risk factor for rooflessness is supported. However, length of rooflessness was more closely related to IQ drop than to current IQ, suggesting that some third factor may be affecting both rooflessness and intellectual functioning. Roofless men with schizophrenia or alcohol problems may be especially at risk of long-term rooflessness.

Adult↗

Teratogenic effects of gravitational changes.

In investigating the effect of gravitational changes on development, it is instructive to think of altered gravity (delta g) as a teratogen--that is, an environmental factor influencing development. Observed effects on skeletal development include: suppression of morphogenesis in centrifuged mouse limb buds; advanced fusion stages in centrifuged mouse palates; smaller crown rump lengths (CRL) and decreased number of pregnancies in centrifuged rats and mice; altered differentiation of growth plates in young growing rats in space; and decreased length of calcified long bone regions in fetal rats exposed to microgravity in utero. These studies show that delta g is able to alter development in vivo and in vitro and suggest that delta g operates, at least in part, at the cellular level.

Animals↗

South Westminster schizophrenia survey. Alcohol use and its relationship to symptoms, tardive dyskinesia and illness onset.

In the context of a prevalence survey of schizophrenia in South Westminster, a questionnaire was administered to 271 patients to assess alcohol-related morbidity. In this epidemiologically based sample, the lifetime prevalence of alcohol abuse was 22.1%. Compared with control patients matched for age and sex, these index cases had a significantly shorter duration of illness. A possible explanation is that drinking may mask the onset of schizophrenia, leading to a delay in diagnosis. The index cases also had significantly higher ratings for hallucinations and for hostility, anxiety and depression, and a greater number of disturbed types of behaviour. The highest levels of alcohol consumption were associated with more severe orofacial dyskinesia, suggesting that alcohol use may be an added risk factor for the development of tardive dyskinesia in some patients. The severity of akathisia was also related to alcohol use, and there were significant relationships between the subjective distress related to akathisia and the level of abuse. A possible interpretation is that alcohol had been used by patients with akathisia to alleviate the associated agitation and dysphoria.

Adult↗

Studies of chondrogenesis in rotating systems.

A great deal of energy has been exerted over the years researching methods for regenerating and repairing bone and cartilage. Several techniques, especially bone implants and grafts, show great promise for providing a remedy for many skeletal disorders and chondrodystrophies. The bioreactor (rotating-wall vessel, RWV) is a cell culture system that creates a nurturing environment conducive to cell aggregation. Chondrocyte cultures have been studied as implants for repair and replacement of damaged and missing bone and cartilage since 1965 [Chesterman and Smith, J Bone Joint Surg 50B:184-197, 1965]. The ability to use large, tissue-like cartilage aggregates grown in the RWV would be of great clinical significance in treating skeletal disorders. In addition, the RWV may provide a superior method for studying chondrogenesis and chondrogenic mutations. Because the RWV is also reported to simulate many of the conditions of microgravity it is a very useful ground-based tool for studying how cell systems will react to microgravity.

Animals↗

Spaceflight and age affect tibial epiphyseal growth plate histomorphometry.

Growth plate histomorphometry of rats flown aboard the Soviet biosatellite COSMOS 2044, a 14-day spaceflight, was compared with that of control groups. In growth plates of flight animals, there was a significant increase in cell number per column and height of the proliferative zone and a reduction in height and cell number in the hypertrophy/calcification zone. No significant differences were found in matrix organization at the ultrastructural level of flight animals, indicating that although spaceflight continues to affect bone growth of 15-wk-old rats, extracellular matrix is not altered in the same manner as seen previously in younger animals. All groups showed growth plate characteristics attributed to aging: lack of calcification zone, reduced hypertrophy zone, and unraveling of collagen fibrils. Tail-suspended controls did not differ from other controls in any of the parameters measured. Our results suggest that growth plates of older rats are less responsive to unloading by spaceflight or suspension than those of younger rats and provide new evidence about the modifying effect of spaceflight on the growth plate.

Aging↗

Histomorphometric and electron microscopic analyses of tibial epiphyseal plates from Cosmos 1887 rats.

Previous studies have shown that the changes seen in the bones of growing rats exposed to microgravity are due in part to changes that occur in the growth plate during spaceflight. In this study, growth plates of rats flown aboard Cosmos 1887 (12.5-day flight plus 53.5-h recovery at 1 g) were analyzed using light and electron microscopy and computerized planimetry. The proliferative zone of flight animals was found to be significantly (P less than or equal to 0.01) larger than that of controls, while the reserve and hypertrophic/calcification zones were significantly reduced. Flight animals also had more cells per column in the proliferative zone than did controls and less in the hypertrophic/calcification region. The total number of cells, however, was significantly greater in flight animals. No difference was found in perimeter or in shape factor, but area was significantly less in flight animals. Electron microscopy showed that collagen fibrils in flight animals were wider than in controls. Since the time required for a cell to cycle through the growth plate is 2-3 days at 1 g, the results reported here represent both the effects of exposure to microgravity and the initial stages of recovery from that exposure.

Animals↗

The effects of gravitational forces on reproduction and development.

It is clear that increased gravitational forces can affect biologic reproduction and development, although exact mechanisms of action have not been established. Except for three studies of male pilot and astronaut fertility, human reproduction and development studies of chronic or acute exposure to micro- or hypergravity environments have not been carried out. Only two reproduction and development studies (both Soviet) have been done under chronic or acute exposure to microgravity. It is unlikely that chronic human exposure to hypergravity will occur except when planets much larger than Earth are colonized. Colonies dependent on reproduction for continued existence probably could not be established on planets with masses significantly dissimilar to Earth because hypergravity or hypogravity are likely to affect reproduction adversely and cause abnormal growth and development. Acute exposures to gravitational changes in the later stages of development appear to be less detrimental, but much remains to be discovered about how gravity affects reproduction and development of mammals, humans in particular. Earth's gravitational force has helped to shape human reproduction and development. Only when the limits of mammalian biology on both sides of 1 g are explored will we be able to determine the extent to which gravity determines biologic structure and function.

Animals↗

X-ray microscopy and X-ray imaging.

Within a framework of an overview of the current status and potential of X-ray microscopy, a description is given of the development of the King's College scanning instrument which produced its first images in September, 1986. The instrument was mounted on the newly-built undulator beam line at the UK Science and Engineering Research Council's SRS synchrotron. There are consequently three sites worldwide where high-resolution X-ray microscopes with zone-plate optics are in operation. The other sites are BESSY-Berlin and NSLS-Brookhaven.

Animals↗

Stereochemistry of iron in deoxyhaemoglobin.

The EXAFS of human deoxyhaemoglobin closely resembles that of a synthetic model in which the displacement of the iron from the mean porphyrin plane is 0.426 +/- 0.004 A, similar to the displacement of 0.56 +/- 0.03 A found by single crystal X-ray analysis of deoxyhaemoglobin. We find the same Fe-N of 2.06 +/- 0.01 A distance as Eisenberger et al., but show that the displacement of the iron from the nitrogen plane cannot be calculated from that distance.

Electron Probe Microanalysis↗