A strong HLA association is seen in coeliac disease [specifically to the
DQ(alpha1*0501,beta1*0201 heterodimer], but this cannot entirely account
for the increased risk seen in relatives of affected cases. One or more
genes at HLA-unlinked loci also predispose to coeliac disease and are
probably stronger determinants of disease susceptibility than HLA. A recent
study has proposed a number of candidate regions on chromosomes 6p23
(distinct from HLA), 6p12, 3q27, 5q33.3, 7q31.3, 11p11, 15q26, 19p13.3,
19q13.1, 19q13.4 and 22cen for the location of a non-HLA linked
susceptibility gene. We have examined these regions in 28 coeliac disease
families by linkage analysis. There was excess sharing of chromosome 6p
markers, but no support for a predisposition locus telomeric to HLA. No
significant evidence in favour of linkage to coeliac disease was obtained
for chromosomes 3q27, 5q33.3, 7q31.3, 11p11, 19p13.3, 19q13.1, 19q13.4 or
22cen. There was, however, excess sharing close to D15S642. The maximum
non-parametric linkage score was 1.99 (P = 0.03). Although the evidence for
linkage of coeliac disease to chromosome 15q26 is not strong, the well
established association between coeliac disease and insulin dependent
diabetes mellitus, together with the mapping of an IDDM susceptibility
locus (IDDM3) to chromosome 15q26, provide indirect support for this as a
candidate locus conferring susceptibility to coeliac disease in some
families.
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Background. Ovine pulmonary valve leaflets and pulmonary arteries have been tissue-engineered (TE) from autologous cells and biodegradable polyglycolic acid (PGA)-polyglactin copolymers. Use of this cell-polymer construct in the systemic circulation resulted in aneurysm formation. This study evaluates a TE vascular graft in the systemic circulation which is based on a new copolymer of PGA and polyhydroxyalkanoate (PHA).
Methods. Ovine carotid arteries were harvested, expanded in vitro, and seeded onto 7-mm diameter PHA-PGA tubular scaffolds. The autologous cell-polymer vascular constructs were used to replace 3–4 cm abdominal aortic segments in lambs (group TE, n = 7). In a control group (n = 4), aortic segments were replaced with acellular polymer tubes. Vascular patency was evaluated with echography. All control animals were sacrificed when the grafts became occluded. Animals in TE group were sacrificed at 10 days (n = 1), 3 (n = 3), and 5 months (n = 3). Explanted TE conduits were evaluated for collagen content, deoxyribonucleic acid (DNA) content, structural and ultrastructural examination, mechanical strength, and matrix metalloproteinase (MMP) activity.
Results. The 4 control conduits became occluded at 1, 2, 55, and 101 days. All TE grafts remained patent, and no aneurysms developed by the time of sacrifice. There was one mild stenosis at the anastomotic site after 5 months postoperatively. The percent collagen and DNA contents approached the native aorta over time (% collagen = 25.7% ± 3.4 [3 months] vs 99.6% ± 11.7 [5 months], p < 0.05; and % DNA = 30.8% ± 6.0 [3 months] vs 150.5% ± 16.9 [5 months], p < 0.05). Histology demonstrated elastic fibers in the medial layer and endothelial specific von Willebrand factor on the luminal surface. The mechanical strain-stress curve of the TE aorta approached that of the native vessel. A 66 kDa MMP-2 was found in the TE and native aorta but not in control group.
Conclusions. Autologous aortic grafts with biological characteristics resembling the native aorta can be created using TE approach. This may allow the development of “live” vascular grafts. 相似文献
In the small intestinal mucosa, four principal epithelial cell lineages are found - the Paneth, goblet, enterocytic, and endocrine cell lineages. These cell lineages are terminally differentiated, non-proliferative, and derive from multipotent stem cells near the bases of the crypts of Lieberkühn. Intestinal metaplasia of the stomach is considered to be a premalignant condition. Since proliferative populations in this condition are not well studied, this feature was examined using double-labelling immunohistochemical and histochemical methods; 20 paraffin blocks of small intestinal mucosa and 24 paraffin blocks of intestinal metaplasia of the human stomach were studied. Double-staining was carried out with MIB-1 as a proliferation marker, with Alcian blue for goblet cells, anti-chromogranin A for endocrine cells, and p-dimethylaminobenzaldehyde-nitrite for Paneth cells. Double-labelling showed that numerous Paneth cells and goblet cells in intestinal metaplasia were in the cell cycle, but endocrine cells appeared non-proliferative. Double-labelled Paneth or endocrine cells were not seen in the control small intestinal mucosa but scanty double-labelled goblet cells were observed in normal intestinal mucosa. In intestinal metaplasia of the stomach, there is evidence of cell-cycle deregulation in the goblet and Paneth cell lineages. These observations have considerable implications for the biology and histogenesis of Paneth cells, goblet cells, and endocrine cells, and the nature of intestinal metaplasia in the gastric mucosa. 相似文献
The present study is the first prospective randomized controlled trial of
the effect of pentoxifylline on future fertility in infertile women with
asymptomatic minimal or mild endometriosis. After completion of a basic
infertility workup and laparoscopy, patients were entered into the study
and randomly allocated to receive either a 12 month course of oral
pentoxifylline (800 mg/day) (n = 30) or an oral placebo (n = 30). Those
patients with other infertility factors were included in the study only if
the factors were correctable and ultimately determined to be
non-contributory. Life-table analysis was used to compare pregnancy rates
between the two groups over a 12 month period that started immediately
after laparoscopy. The 12 month actuarial overall pregnancy rates were 31
and 18.5% in the pentoxifylline and placebo groups respectively. However,
this difference was not statistically significant by the chi(2)-test.
Similarly, the Cox regression method showed no differences between the
hazard of pregnancy in the two groups studied (odds ratio, 0.56; 95%
confidence interval, 0.18-1.67). Therefore, there is no evidence from this
study that immunomodulation with pentoxifylline aids fertility in those
women with minimal or mild endometriosis. Further studies including more
infertile patients with endometriosis are desirable in order to confirm our
results.
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HECD-1 monoclonal antibody has been used to localize E-cadherin, a calcium-dependent cell–cell adhesion molecule, in microwave-treated, paraffin-embedded sections from 53 cases of cervical intraepithelial neoplasia (CIN) (11 CIN I, 22 CIN II, and 20 CIN III), 16 invasive cervical squamous cell carcinomas, and seven metastases. In normal cervix, E-cadherin was expressed on the cell membrane of basal and parabasal cells. Cytoplasmic staining was present in occasional basal cells only. In CIN, the presence and localization of cytoplasmic E-cadherin were found to be significantly correlated with the grade of the CIN lesion. In squamous cell carcinomas, reduced membranous and increased cytoplasmic staining was seen with worsening differentiation. Loss of membranous E-cadherin expression was also detected in 4/7 metastatic deposits. E-cadherin expression (120 kD form on Western blotting) was seen in human cervical carcinoma cell lines (HT3, ME180, C41, Caski) that maintained the ability to aggregate in a homotypic adhesion assay and showed a typical epithelial morphology. E-cadherin-negative cell lines (Hela, SiHa, C33A) did not show adhesion. HOG-1 was the only E-cadherin-negative cell line which showed a significant degree of cell–cell aggregation. These data indicate that loss of membranous E-cadherin expression may represent one of the abnormalities underlying loss of cell polarity and differentiation which characterize CIN and invasive cervical cancer. 相似文献