2004 Summer Meeting - Amsterdam - The Pathological Society of ...

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Upregulation of nox2 expression in both acute and chronic
hypoxia
C. Meischl 1 , P.A.J. Krijnen 1 , S.A.G. Cillessen 1 , R. Musters 2 ,
W.S. Simonides 2 , C.E. Hack 3 , D. Roos 3 , H.W.M. Niessen 1
1 VU University Medical Center Department of Pathology, Amsterdam,
Netherlands, 2 VU University Medical Center Department of Physiology,
Amsterdam, Netherlands, 3 Sanquin Research at CLB, and Landsteiner
Laboratory, Academic Medical Centre, Amsterdam, Netherlands
NADPH oxidase-generated reactive oxygen species have been shown to play an
important role in the pathophysiology of the heart in general. We previously
have shown in human autopsy material that nox2 is upregulated following acute
myocardial infarction.
We have now extended these findings to different in vitro and in vivo models of
ischemia. In H9c2 cells, a rat cardiomyocyte-derived cell line, we observed
upregulation of nox2 expression after 1-2 hours of metabolically induced
ischemia, which was further increased after subsequent reperfusion. This
upregulation colocalized with a concomitantly increased generation of reactive
oxygen species. Furthermore, in an in vivo rat model of chronic hypoxia, we
also observed a markedly increased expression of nox2 in cardiomyocytes.
These data show that upregulation of nox2 is induced in cardiomyocytes by
ischemia and/or reperfusion, both in acute and chronic alterations. Our present
efforts are directed at elucidating the cell-biological consequences of the
observed upregulation of the NADPH oxidase and the increased generation of
reactive oxygen species.
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Human Pulmonary Microvessels Express Abundant
Myoendothelial Gap Junctions Composed Of Connexin 40
M Koslowski 1 , WR Roche 1 , K Stuart-Smith 2
1 Department of Cellular Pathology, Southampton General Hospital,
Southampton, United Kingdom, 2 Department of Anaesthesia, Glan Clwyd
Hospital, Rhyl, United Kingdom
Endothelium-derived Hyperpolarizing Factor (EDHF), generated by the
endothelium of small blood vessels, initiates relaxation of the underlying
smooth muscle. Direct contact between endothelial and smooth muscle cells in
the form of gap junctions may be necessary for the EDHF-signal transfer. The
present study used electron microscopy and immunohistochemistry to
demonstrate direct myoendothelial contacts in human pulmonary microvessels.
Electron microscopy demonstrated close membrane appositions between
endothelial and smooth muscle cells with focal membrane fusion. All
appositions were formed by membrane projections from smooth muscle cells
through the internal elastic lamina. To determine whether these appositions
contained gap junctions, immunohistochemistry was carried out for connexins
37, 40 and 43, the gap junction proteins commonly found in blood vessels.
Connexin 37 was occasionally present in endothelial cells. Connexin 43 was
absent. By contrast, connexin 40 was found abundantly on the abluminal side of
endothelial cells and in the adjacent smooth muscle cells, implicating the
presence of myoendothelial gap junctions. These results demonstrate for the
first time that electron microscopic evidence of myoendothelial gap junctions
can be correlated with immunohistochemical evidence of such junctions in
blood vessels. Such structures may provide a pathway for the EDHF-signal
transfer from the endothelium to the smooth muscle.
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Tissue Consenting For Surgically Removed Tissue. Has
Performance Improved One Year On?
J M Wheeler 1 , M Agarwal 1 , J Sugden 1 , M Bladon 1 , P Quirke
2
1 Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom, 2 LTH
NHS Trust & Academic Unit of Pathology, Leeds University, Leeds,
United Kingdom
The Human Tissue Act suggests that surgically removed tissue requires consent
for research. In Autumn 2002 we incorporated a section regarding use of tissue
into the standard national surgical consent form. A total of 5840 consent forms
were audited from Oct/Nov 2002 & Oct/Nov 2003. Initially the audits looked at
the number of histology requests accompanied by consent forms. This had
increased from 51% to 70% after one year. Few other changes occurred over
this period. In 2003, 56% (55% - 2002) had completed the tissue section, 34%
(36% - 2002) were blank and 10% (9% - 2002) were partially completed.
Rejection rate for public health monitoring improved, falling from 10% to 4%.
Rejection rates for the use of tissue for future diagnosis remained the same at
4% and for teaching/research remained at 5%. One consultant achieved a 100%
rejection rate on all sections.
Conclusions: Receipt of consent forms has increased to 70% but only 56% of
forms received were properly filled in. A lack of improvement in completing
the tissue section, plus anomalies in the rejection rate indicates a significant
need for education and training of clinicians, if this method is to be used
routinely by the NHS.
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The Standing of UK Histopathology Research 1997-2002
G Lewison 1 , K Wilcox-Jay 1 , NA Wright 2
1 City University, London, United Kingdom, 2 Histopathology Unit, Cancer
Research (UK), London, United Kingdom
INTRODUCTION: We have attempted a quantitative bibiiometric assessment
of the UK's research in histopathology. METHODS: histopathology and its
subject areas were defined by means of ‘filters’ based on specialist journals and
title words; the filters were developed by specialist histopathologists. The
‘basic’ or ‘clinical nature of each publication was assessed and a measurement
made of its ‘potential impact category’ (PIC). The results were compared both
within the UK and relative to 11 OECD countries. RESULTS: Worldwide
histopathology output has remained static, compare with a steady growth in
biomedicine, with the UK’s contribution at 10% below its average presence.
Neuropathology, genetics and cardiovascular pathology emerged as the largest
output, and ophthalmic pathology the smallest. Output volume in breast,
gynaecological and osteoarticular and soft tissue pathology was strong, but
hepatopathology was very weak. Genetic research proved most basic and
cytopathology most clinical, and the bias of all UK research was more clinical
than the other countries. UK papers had a PIC higher than the world average,
although behind the USA, Netherlands, Switzerland and Canada. Only 59% of
papers acknowledged funding source, with more basic papers acknowledging
support than clinical papers and charitable funding was more prominent than
government research council funding. , In the UK the leading centres were
London (WC 11.3%, W 8.3% SE 7.7 % and SW 5.9%), Oxford 8% and
Manchester 6%; in addition all these centres published more in histopathology
than biomedicine overall. However, centres such as Cambridge, Aberdeen,
Glasgow and Edinburgh were less committed to histopathology, with only
Dundee in Scotland having a higher presence (3.1 v. 2.1%). A postal survey of
150 histopathology researchers revealed a good correlation between mean
relative esteem value (REV) and journal citation scores (r 2 = 0.60). The UK
appeared at the lower middle rank of REV, below USA, Switzerland and
Canada, but above Spain and Sweden.
CONCLUSIONS: The data do provide data on the quantity of output, with
insights into quality within methodological constraints.
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