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51.
52.
Arif JM; Gairola CG; Glauert HP; Kelloff GJ; Lubet RA; Gupta RC 《Carcinogenesis》1998,19(8):1515-1517
The present study investigated the effects of dietary oltipraz on cigarette
smoke-related lipophilic DNA adduct formation. Female Sprague- Dawley rats
were exposed daily to sidestream cigarette smoke in a whole- body exposure
chamber 6 h/day for 4 consecutive weeks. One group of rats was maintained
on control diet while another group received the same diet supplemented
with either a low (167 p.p.m.) or high (500 p.p.m.) dose of oltipraz,
starting 1 week prior to initiation of smoke exposure until the end of the
experiment. Analysis of lipophilic DNA adducts by the nuclease P1-mediated
32P-post-labeling showed up to five smoke-related adducts. Adduct no. 5
predominated in both the lung and the heart while adduct nos 3 and 2
predominated in the trachea and bladder, respectively. Quantitative
analysis revealed that the total adduct level was the highest in lungs
(270+/-68 adducts/10(10) nucleotides), followed by trachea (196+/-48
adducts/10(10) nucleotides), heart (141+/-22 adducts/10(10) nucleotides)
and bladder (85+/-16 adducts/10(10) nucleotides). High dose oltipraz
treatment reduced the adduct levels in lungs and bladder by >60%, while
the reduction in lungs in the low-dose group was approximately 35%. In
trachea, the effect of low and high dietary oltipraz on smoke DNA adduction
was equivocal, while smoke-related DNA adducts in the heart were minimally
inhibited by high-dose oltipraz. In a repeat experiment that employed a
3-fold lower dose of cigarette smoke, oltipraz (500 p.p.m.) was found to
inhibit the formation of DNA adducts in rat lungs and trachea by 80 and
65%, respectively. These data clearly demonstrate a high efficacy of
oltipraz in inhibiting the formation of cigarette smoke-induced DNA adducts
in the target tissues.
相似文献
53.
van Kranen HJ; van Iersel PW; Rijnkels JM; Beems DB; Alink GM; van Kreijl CF 《Carcinogenesis》1998,19(9):1597-1601
The variation in colorectal cancer (CRC) incidence worldwide strongly
suggests a role for dietary influences. Based on epidemiological data,
protective effects of vegetables and fruit intake on CRC are widely
claimed, while other data indicate a possible increased CRC risk from
(higher) dietary fat intake. Therefore, we have investigated single and
interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in
the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this
study, four different diets (A-D) were compared, which were either low in
fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In
addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced
by a freeze-dried VFM. The diets were balanced so that they only differed
among each other in fat/carbohydrate content and the presence of specific
plant-constituents. Because the initiation of intestinal tumors in ApcMin
mice occurs relatively early in life, exposure to the diets was started in
utero. Without the addition of VFM, mice maintained at a high-fat diet did
not develop significantly higher numbers of small or large intestinal
adenomas than mice maintained at a low-fat diet. VFM added to a low-fat
diet significantly lowered multiplicity of small intestinal polyps (from
16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male
ApcMin mice only. Strikingly, addition of VFM to female mice maintained on
a low-fat diet and to both sexes maintained on a high-fat diet
significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7
polyps/mouse). In conclusion, our results indicate that neither a lower fat
intake nor consumption of VFM included in a high-fat diet decreases the
development of polyps in mice genetically predisposed to intestinal tumor
development.
相似文献
54.
55.
Van Den Pol AN Vieira J Spencer DD Santarelli JG 《The Journal of comparative neurology》2000,427(4):559-580
Cytomegaloviruses (CMVs) are species-specific large double-stranded DNA viruses. Mouse and human CMVs have a similar morphology, similar gene sequence, and exert similar cellular effects, but the replication of the virus outside its primary host species is limited. This may confer upon CMV certain advantages for expression of foreign genes or cellular labels in brain cells of nonhost species. We examined the ability of recombinant mouse (m)CMV expressing green fluorescent protein (GFP) to serve as a vector for transgene expression in developing neurons and glia outside the normal host species. For comparative purposes, 11 species were examined. Mouse CMV reporter gene expression was particularly strong in the developing brain of its normal host species, mouse, where it replicated in cultures and brain slices, leading to cell death. All mammalian species tested (human, rat, gerbil, hamster, mouse) showed reporter gene expression after mCMV infection. High levels of mCMV infection were also found in chicken central nervous system cells in vitro, and a low level of mCMV expression was found after an initial delay in turtle neurons and glia. No mCMV reporter gene expression was found in frog cells or aplysia neurons or glia or in drosophila or fungal cells. Infection of nonmouse neurons by low concentrations of mCMV led to strong expression of GFP in dendrites and axons with normal morphology. Despite the lack of replication, high doses of mCMV induced morphologic changes in neurons and glia from hamster and rat brain slices, leading to cells rounding up, and to the formation of giant cells consisting of an aggregate of many cells fused together into a syncytium. In contrast, in human hippocampal slices, GFP-expressing cells infected with mCMV had a relatively normal appearance 12 days after inoculation. To determine whether a CMV from another species could serve as a vector for gene transfer, a recombinant human CMV-expressing GFP was used for transgene expression in rat brain cells in vitro. Cytomegaloviruses thus have potential as useful vectors for gene transfer and labeling central nervous system cells, with the actions of CMV being dependent on a number of factors. 相似文献
56.
57.
W. Andonotopo M. Stanojevic A. Kurjak G. Azumendi JM Carrera 《The Ultrasound Review of Obstetrics & Gynecology》2004,4(2):103-114
The aim of this paper was to review the clinical applications of four-dimensional ultrasonography in the assessment of fetal behavior. With the use of a computerized database, articles on three-dimensional ultrasonography were reviewed. Several applications of dynamic three-dimensional ultrasonography have been reported, including imaging of fetal movements, facial expression and fetal hand movements. The importance of the assessment of fetal behavior by four-dimensional sonography is stressed. Four-dimensional sonography seems to be a useful imaging tool for clinical problem solving in perinatology, especially in observing the development of the central nervous system in utero. 相似文献
58.
Although cognitive impairments are well recognized in patients with schizophrenia, it is unclear which impairments are due to a genetic predisposition and which are caused by secondary disease effects or phenotype. The aim of this study is to investigate the possible relationship between genetic vulnerability to schizophrenia and cognitive functioning. Three groups of subjects were compared: 14 patients with schizophrenia, 15 healthy siblings and 32 healthy control subjects. All subjects were tested neuropsychologically. The raw test data were rescaled to standard equivalents (z-scores). Subjects' z scores on tests assessing the same cognitive domain were clustered and analyzed. Differences in cognitive functioning were found in the domains of abstraction, attention, executive functioning, spatial memory, and sensory-motor functioning. The schizophrenic probands were impaired on all these five domains whereas the healthy probands showed impairments on executive functioning and partially on sensory-motor functioning. Furthermore, for spatial memory the significant finding could mainly be attributed to impaired functioning in the patients, but not healthy siblings or control subjects, whereas for executive functioning patients and healthy siblings seemed equally impaired as compared to control subjects. The planning time of the Tower of London (TOL) and the initiation time of the Motor Planning Task (MPT) were used for measures of executive functioning, while the 'time to move of the Motor Planning Task' was used as measures of sensory motor functioning. These results suggest that the cognitive abnormalities in schizophrenia that may be related to genotype are represented in the domain of executive functioning and to some extent in the domain of sensory-motor functioning. 相似文献
59.
Anna van Rhenen Nicole Feller Angèle Kelder August H Westra Elwin Rombouts Sonja Zweegman Marjolein A van der Pol Quinten Waisfisz Gert J Ossenkoppele Gerrit Jan Schuurhuis 《Clinical cancer research》2005,11(18):6520-6527
PURPOSE: In CD34-positive acute myeloid leukemia (AML), the leukemia-initiating event originates from the CD34(+)CD38(-) stem cell compartment. Survival of these cells after chemotherapy may lead to minimal residual disease (MRD) and subsequently to relapse. Therefore, the prognostic impact of stem cell frequency in CD34-positive AML was investigated. EXPERIMENTAL DESIGN: First, the leukemogenic potential of unpurified CD34(+)CD38(-) cells, present among other cells, was investigated in vivo using nonobese diabetic/severe combined immunodeficient mice transplantation experiments. Second, we analyzed whether the CD34(+)CD38(-) compartment at diagnosis correlates with MRD frequency after chemotherapy and clinical outcome in 92 AML patients. RESULTS: In vivo data showed that engraftment of AML blasts in nonobese diabetic/severe combined immunodeficient mice directly correlated with stem cell frequency of the graft. In patients, a high percentage of CD34(+)CD38(-) stem cells at diagnosis significantly correlated with a high MRD frequency, especially after the third course of chemotherapy. Also, it directly correlated with poor survival. In contrast, total CD34(+) percentage showed no such correlations. CONCLUSIONS: Both in vivo data, as well as the correlation studies, show that AML stem cell frequency at diagnosis offers a new prognostic factor. From our data, it is tempting to hypothesize that a large CD34(+)CD38(-) population at diagnosis reflects a higher percentage of chemotherapy-resistant cells that will lead to the outgrowth of MRD, thereby affecting clinical outcome. Ultimately, future therapies should be directed toward malignant stem cells. 相似文献
60.
A Jamieson GC Inglis M Campbell R Fraser JM Connell 《Archives of disease in childhood》1994,71(1):40-43
Glucocorticoid suppressible hyperaldosteronism (GSH) is an uncommon form of dominantly inherited hypertension. Presentation with hypertension and complications such as stroke in early life are well recognised. The use of a simple genetic test carried out on blood or placenta facilitates the detection of infants and children with GSH before the development of hypertension, allowing prompt treatment of hypertension if it occurs, and an opportunity to study the effects of growth and environmental influences on the progression of the condition. 相似文献