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761.
Kadow JF Regueiro-Ren A Weinheimer SP 《Current opinion in investigational drugs (London, England : 2000)》2002,3(11):1574-1579
Viruses are estimated to be linked to at least 15% of human cancers. Hepatitis B and C viruses, human papilloma viruses, Epstein-Barr virus, human herpes virus-8 and human T-cell leukemia virus have been definitively linked to human cancer. A brief overview of the molecular mechanisms of carcinogenesis elucidated for these viruses and antiviral approaches which may provide clues to reducing the occurrence or progression of the resulting virally derived cancers are described. 相似文献
762.
Laurentius CJ Slobbe Onyebuchi A Arah Agnes de Bruin Gert P Westert 《BMC health services research》2008,8(1):52
Background
Patterns in time, place and cause of death can have an important impact on calculated hospital mortality rates. Objective is to quantify these patterns following myocardial infarction and stroke admissions in Dutch hospitals during the period 1996–2003, and to compare trends in the commonly used 30-day in-hospital mortality rates with other types of mortality rates which use more extensive follow-up in time and place of death. 相似文献763.
764.
Objective To assess the feasibility, efficiency and selectivity of adenovirus- mediated ge ne transfer to local arterial wall by protein- coated metallic stent. Methods A replication- defective recombinant adenovirus carrying the Lac Z reporter gene for nuclear- specific β- galactosidase (Ad- βgal) was used in this study. Th e coating for metallic stent was made by immersing it in a gelatin solution cont aining crosslinker. The coated stents were mounted on a 4. 0 or3. 0mmpe rcutaneous transluminal coronary angioplasty (PTCA) balloon and submersed into a high- titer Ad- βgal viral stock (2×10(10)pfu/ml) for 3 min, and then im planted into the carotid arteries in 4 mini- swines and into the left anterior d escending branch of the coronary artery in 2 mini- swines via 8F large lumen gui ding catheters. The animals were sacrificed7 (n=4), 14 (n=1) and 21 (n=1) days after implantation, respectively. The β- galactosidase expression was as sessed by X- gal staining. Results The results showed that the expression of transgene was detected in all animal. In 1 of carotid artery with an intact intima, the β- gal expression was l imited to endothelial cells. In vessels with denuded endothelium, gene expressi on was found in the sub- intima, media and adventitia. The transfection efficie ncy of medial smooth muscle cells was 38. 6%. In 2 animals sacrificed 7 days af ter transfection, a microscopic examination of X- gal- stained samples did not s how evidence oftransfection in remote organs and arterial segments adjacent to the treated arterial site.Conclusions Adenovirus- mediated arterial gene transfer to endothelial, smooth muscle cells and adventitia by protein- coated metallic stent is feasible. The transfection efficiency is higher. The coated stent may act as a good carrier of adenovirus - mediated gene transfer and have a potential to prevent restenosis following PT CA. 相似文献
765.
Grimes A; Hearn CJ; Lockhart P; Newgreen DF; Mercer JF 《Human molecular genetics》1997,6(7):1037-1042
The brindled mouse mutant (Mo(br)) is the closest animal model of the human
genetic copper deficiency, Menkes disease, which is presumed to be due to a
mutation at the X-linked mottled locus (Mo). The mutant mice are
hypopigmented and die at around 15 days after birth, but can be saved by
treatment with copper before the 10th postnatal day. Menkes disease has
been shown to be due to mutations of the gene ATP7A which encodes P-type
ATPase (referred to here as MNK). MNK is likely to function in copper
efflux from cells, but the full range of its biological activity is not
fully understood. The nature of the mutation in the brindled mouse is of
importance in our understanding of the role of MNK and for devising
treatment strategies for Menkes disease. Here we show that the brindled
mouse has a deletion of two amino acids in a highly conserved, but
functionally uncharacterized, region of Mnk. Comparison with the Ca ATPases
suggests this region may be involved in conformational changes associated
with the E1/E2 transition fundamental to the action of P-type ATPases. We
also describe the first Western blot data for Mnk in tissues, and these
show normal levels of Mnk in mutant and brindled kidneys but none in liver.
In the kidney, immunohistochemistry demonstrated Mnk in the proximal and
distal tubules, the distribution is identical in mutant and normal. This
distribution is consistent with Mnk being involved in copper resorption
from the urine.
相似文献
766.
Warnich L; Kotze MJ; Groenewald IM; Groenewald JZ; van Brakel MG; van Heerden CJ; de Villiers JN; van de Ven WJ; Schoenmakers EF; Taketani S; Retief AE 《Human molecular genetics》1996,5(7):981-984
Mutation analysis of genomic DNA samples obtained from 17 unrelated South
African patients with variegate porphyria (VP) revealed three novel
missense mutations in the protoporphyrinogen oxidase (PPOX) gene. A common
C to T transition at nucleotide position 452 (R59W) was identified in 15 of
the patients analysed, while base changes at positions 336 (H20P) and 779
(R168C) were identified in the remaining two patients. Using protein
analysis software we were able to predict that all three mutations have a
similar biophysical effect on the protein, being the disturbance of
amphiphatic regions within the protein, which might result in misfolding of
the protein. Mutation R59W, identified in the majority of South African VP
families, was shown to create a Styl restriction site, while mutation R168C
would abolish a Dsal restriction site in genomic DNA of affected
individuals. As 100% of the index patients analysed were molecularly
characterized, the combined use of restriction enzyme and single-strand
conformation polymorphism (SSCP) analysis now allows a rapid and accurate
diagnosis of VP in South Africa. Mutation R59W was furthermore shown to be
in association with one of four potential haplotypes defined by two newly
described polymorphisms in exon 1 of the PPOX gene. Our molecular data thus
strongly support the founder hypothesis for VP in South Africa.
相似文献
767.
Frans A Hol Nathalie MJ van der Put Monique PA Geurds Sandra G Heil Frans JM Trijbels Ben CJ Hamel Edwin CM Mariman Henk J Blom 《Clinical genetics》1998,53(2):119-125
It is now well recognized that periconceptional folic acid or folic acid containing multivitamin supplementation reduces the risk of neural tube defects (NTDs). Recently we were able to show that homozygosity for a thermolabile variant of the enzyme methylenetetrahydrofolate reductase is associated with an increased risk for spina bifida in patients recruited from the Dutch population. However, this genetic risk factor could not account for all folic acid preventable NTDs. In an attempt to identify additional folate related enzymes that contribute to NTD etiology we now studied the methylenetetrahydrofolate dehydrogenase gene on chromosome 14q24 which encodes a single protein with three catalytic properties important in the folate metabolism. The cDNA sequence of 38 familial and 79 sporadic patients was screened for the presence of mutations by single strand conformation polymorphism (SSCP) analysis followed by sequencing. Two amino acid substitutions were identified. The first one (R293H) was detected in a patient with familial spina bifida and not in 300 control individuals. The mutation was inherited from the unaffected maternal grandmother and was also present in two younger brothers of the index patient, one of them displaying spina bifida occulta and the other being unaffected. The second change turned out to be an amino acid polymorphism (R653Q) that was present in both patients and controls with similar frequencies. Our results so far provide no evidence for a major role of the methylenetetrahydrofolate-dehydrogenase (MTHFD) gene in NTD etiology. However, the identification of a mutation in one family suggests that this gene can act as a risk factor for human NTD. 相似文献
768.
TM Fandel M Pfnür SC Schäfer P Bacchetti FW Mast C Corinth M Ansorge SW Melchior JW Thüroff CJ Kirkpatrick H‐A Lehr 《The Journal of pathology》2008,216(2):193-200
In the histomorphological grading of prostate carcinoma, pathologists have regularly assigned comparable scores for the architectural Gleason and the now‐obsolete nuclear World Health Organization (WHO) grading systems. Although both systems demonstrate good correspondence between grade and survival, they are based on fundamentally different biological criteria. We tested the hypothesis that this apparent concurrence between the two grading systems originates from an interpretation bias in the minds of diagnostic pathologists, rather than reflecting a biological reality. Three pathologists graded 178 prostatectomy specimens, assigning Gleason and WHO scores on glass slides and on digital images of nuclei isolated out of their architectural context. The results were analysed with respect to interdependencies among the grading systems, to tumour recurrence (PSA relapse > 0.1 ng/ml at 48 months) and robust nuclear morphometry, as assessed by computer‐assisted image analysis. WHO and Gleason grades were strongly correlated (r = 0.82) and demonstrated identical prognostic power. However, WHO grades correlated poorly with nuclear morphology (r = 0.19). Grading of nuclei isolated out of their architectural context significantly improved accuracy for nuclear morphology (r = 0.55), but the prognostic power was virtually lost. In conclusion, the architectural organization of a tumour, which the pathologist cannot avoid noticing during initial slide viewing at low magnification, unwittingly influences the subsequent nuclear grade assignment. In our study, the prognostic power of the WHO grading system was dependent on visual assessment of tumour growth pattern. We demonstrate for the first time the influence a cognitive bias can have in the generation of an error in diagnostic pathology and highlight a considerable problem in histopathological tumour grading. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
769.
Only hydrosalpinges visible on ultrasound are associated with reduced implantation and pregnancy rates after in-vitro fertilization 总被引:3,自引:10,他引:3
de Wit W; Gowrising CJ; Kuik DJ; Lens JW; Schats R 《Human reproduction (Oxford, England)》1998,13(6):1696-1701
A retrospective analysis of clinical and laboratory data was made of all
in-vitro fertilization (IVF) patients with tubal pathology who had their
first ever embryo transfer cycle between January 1st, 1992 and September
1st, 1996. The aim of the study was to determine the effect of the presence
of a hydrosalpinx, whether or not visible by ultrasound, on pregnancy,
multiple pregnancy and implantation rates in our patient population. The
IVF success rate was also analysed by calculating cumulative ongoing
pregnancy rates of the same patient group using the lifetime table
approach. In the presence of an ultrasound-visible hydrosalpinx, rates of
pregnancy and multiple pregnancy appeared reduced, but the differences were
not significant. The rates of implantation, clinical implantation and
ongoing implantation were significantly lower in the presence of an
ultrasound- visible hydrosalpinx (odds ratios 0.33-0.46, C.I. 0.21-0.96).
The cumulative chance of achieving an ongoing pregnancy after one or more
IVF cycles was significantly reduced in the presence of an ultrasound-
visible hydrosalpinx (relative hazard 0.36, C.I. 0.22-0.59). In the
presence of a hydrosalpinx not visible by ultrasound the IVF outcome was
not reduced. This retrospective study confirms that patients with
hydrosalpinges have an impaired IVF outcome. Unique to this study and
previously unobserved is the finding that there is a subgroup of patients
with hydrosalpinges, those with ultrasound-visible hydrosalpinges, which is
exclusively responsible for this impaired outcome.
相似文献
770.
Prognostic factors for an unsatisfactory primary methotrexate treatment of cervical pregnancy: a quantitative review 总被引:17,自引:0,他引:17
Hung TH; Shau WY; Hsieh TT; Hsu JJ; Soong YK; Jeng CJ 《Human reproduction (Oxford, England)》1998,13(9):2636-2642
To determine the risks when the primary methotrexate (MTX) treatment of
cervical pregnancy has an unsatisfactory outcome, we conducted a Medline
search on relevant literature published from January 1983 to June 1997. The
search yielded 28 publications of 48 cases of cervical pregnancy. These and
four new cases from our institutions were used in our study. A cervical
pregnancy that presented with a serum beta-human chorionic gonadotrophin
concentration of > or = 10,000 mIU/ml [odds ratio (OR) 10.82, 95%
confidence interval (CI) 2.59, 45.14], gestational age at > or = 9 weeks
(OR 6.44, 95% CI 1.46, 28.52), embryonic cardiac activity (OR 14.29, 95% CI
2.95, 76.92), and crown- rump length of >10 mm (OR 13.33, 95% CI 1.46,
120.48) was considered to be associated with a higher unsatisfactory rate
of primary MTX treatment. A concomitant feticide was found to enhance the
therapeutic effect of MTX treatment if embryonic cardiac activity was
evident (OR 0.13, 95% CI 0.02, 0.68). Administration of a high dose of MTX
did not seem to be more effective than a lower one. Our findings supported
some previous observations and, more importantly, provided useful clinical
information in selecting appropriate candidates for MTX treatment in cases
of cervical pregnancy.
相似文献