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31.
32.
DNA diagnostics: goals and challenges 总被引:2,自引:0,他引:2
Mathew CG 《British medical bulletin》1999,55(2):325-339
The exponential increase in the discovery of human disease genes over the past 10 years has transformed DNA diagnostics from a minor research-based activity to a major professional operation. Mutation testing and linkage analysis are now used to provide prenatal or postnatal diagnosis for a wide range of monogenic disorders, but robust automated procedures for scanning disease genes for mutations are not yet available. The discovery of genes which confer susceptibility to common disorders is likely to create demand for high throughput testing for specific mutations or clinically relevant polymorphisms. Widespread genetic testing must be supported by adequate genetic counselling and by education of healthcare professionals in order to ensure the appropriate application of this information for the benefit of patients and their families. 相似文献
33.
A histopathologically proven case of cerebral toxoplasmosis in a young HIV positive patient has been presented. The clinical problems in management are highlighted. 相似文献
34.
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
35.
Angiogenesis during tumor progression in the oral cavity is related to reduced apoptosis and high tumor cell proliferation 总被引:2,自引:0,他引:2
D. Ravi K. Ramadas B.S. Mathew K.R. Nalinakumari M.K. Nair M.R. Pillai 《Oral oncology》1998,34(6):543-548
Angiogenesis, the growth of new blood vessels, is believed to aid tumor progression and metastasis. Tumor progression is also influenced by the extent of proliferation and apoptosis. This study, therefore, analyzed in lesions of the oral cavity, the significance of angiogenesis in relation to apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation defined by cyclin D1 expression. Results from this study suggest that angiogenesis increases as histological abnormality increases in the oral mucosa. The expression of apoptosis regulatory proteins also appears to be altered in a histologically dependent manner. The correlation seen between CD34 expression, cyclin D1 and TUNEL reactive cells suggests that increased angiogenesis, decreased apoptosis and deregulated proliferation occur simultaneously during tumor progression in the oral mucosa. Presence of a mutant p53, increased bcl-2 expression and altered bax expression are also involved in this complex process. 相似文献
36.
Mutation of the p53 tumor suppressor gene in spontaneously occurring osteosarcomas of the dog 总被引:8,自引:0,他引:8
Inactivation of the p53 tumor suppressor gene has been implicated in the
pathogenesis of numerous human cancers, including osteosarcomas.
Appendicular osteosarcomas of the dog appear to be a good model for their
human equivalent with regard to biologic behavior, epidemiology and
histopathology. We individually screened exons 5-8 of the p53 gene for
mutations in 15 canine appendicular osteosarcomas using 'Cold' SSCP to
compare the role of this gene in human and canine osteosarcoma
tumorigenesis. Seven of the tumors (47%) exhibited point mutations, with
one tumor possessing two mutations within different exons. Of these, seven
were missense mutations and the eighth was a 'silent' mutation potentially
affecting the exon 6-7 splicing region. Five of the missense mutations were
located in highly conserved regions IV and V, while another corresponded
with the highly conserved codon 220 mutational hotspot located outside the
conserved domains. The locations and types of mutations were nearly
identical to those reported in human cancer. These findings provide strong
evidence of the involvement of p53 mutations in the development of canine
appendicular osteosarcomas. Canine osteosarcomas appear to be a promising
model for their human equivalent on a clinical, pathologic, and molecular
level.
相似文献
37.
38.
Robert L Rubin Tracee M Hermanson Edward J Bedrick Jacob D McDonald Scott W Burchiel Mathew D Reed Wilmer L Sibbitt 《Toxicological sciences》2005,87(1):86-96
Several studies have found that smoking cigarettes is a risk factor for systemic lupus erythematosus (SLE). To examine this issue in a mouse model, we subjected pre-autoimmune MRL-lpr/lpr mice for 4 weeks to cigarette smoke to provide standardized smoke effluents equivalent to moderate or to heavy smoking habits for people. The spontaneous production of IgG anti-chromatin but not IgM anti-chromatin, anti-denatured DNA, or rheumatoid factor antibodies was lower in mice exposed to 250 mg/m3 particulates from mainstream smoke, and this suppression of autoimmunity was sustained for 8 weeks (p < 0.02). In contrast to control mice anti-chromatin activity in smoke-exposed mice began to increase in 16-week-old mice, reaching levels at 6 months that were two- to three-fold higher than controls for IgG (p < 0.03) and 10-fold higher for IgM (p < 0.001). There was no significant effect on total IgG or IgM. In newly diagnosed SLE patients, smoking was negatively correlated with IgG anti-DNA antibodies (p < 0.03). However, of nine patients who discontinued smoking prior to diagnosis, eight had elevated IgG anti-DNA compared to 29/79 never smokers and 9/31 smokers (p < 0.01 compared to former smokers). Inhaled cigarette smoke appears to have a long-lasting immunosuppressive effect on T-cell-dependent autoimmune responses, although autoantibodies increase to supra-elevated levels after the suppressive effect has abated. 相似文献
39.
Thierry M Muanza Ana P Cotrim Mathew McAuliffe Anastasia L Sowers Bruce J Baum John A Cook Felix Feldchtein Paul Amazeen C Norman Coleman James B Mitchell 《Clinical cancer research》2005,11(14):5121-5127
PURPOSE: Optical coherence tomography (OCT) imaging was evaluated to determine if radiation-induced mucosal damage could be noninvasively monitored in real time and correlated with histopathologic findings. EXPERIMENTAL DESIGN: Female C3H mice, ages 7 to 9 weeks, four per group, were immobilized in a custom-made Lucite jig and received 0, 15, 22.5, and 25 Gy in a single fraction to their oral cavity. OCT images were acquired of proximal, middle, and distal aspects of the dorsum of the tongue on days 0, 1, 3, 5, and 7 post-irradiation. Animals were sacrificed on day 7 and samples taken for histologic evaluation. OCT images were visually examined and also quantified by image analysis and compared with histologic findings. RESULTS: Tongues removed 7 days post-irradiation showed no visible damage; however, upon staining with toluidine blue, ulcers at the base of the tongue became visible (100% for 25 Gy, 75% after 22.5 Gy, and 0% after 15 Gy). Visual inspection of OCT images qualitatively compared with histologic findings and quantitative image analysis of the OCT images (effective light penetration depth) revealed significant changes 7 days post-irradiation compared with unirradiated controls for the base of the tongue. CONCLUSIONS: OCT allows for direct noninvasive real-time acquisition of digitally archivable images of oral mucosa and can detect radiation-induced changes in the mucosa before visual manifestation. OCT may be a useful technique to quantify subclinical radiation-induced mucosal injury in experimental chemoradiation clinical trials. 相似文献
40.
Lantana camara is used in herbal medicine for the treatment of skin itches, as an antiseptic for wounds, and externally for leprosy and scabies. The objective of our study was to investigate excision wound healing activity of the leaf extract of L. camara in rats. The animals were divided into two groups of 12 each in both the models. The test group animals were treated with the aqueous extract of L. camara (100 mg/kg/day) topically and the control group animals were left untreated. Wound healing efficacy was measured by determining the morphological and biochemical parameters. Wound healing time, wound contraction and synthesis of collagen were monitored periodically. Antimicrobial activities of the extract against the microorganisms were also assessed. Treatment of the wounds with extract enhanced significantly the rate of wound contraction (98%), synthesis of collagen and decreased mean wound healing time. These studies demonstrate that L. camara is effective in healing excision wounds in the experimental animal and could be evaluated as a therapeutic agent in tissue repair processes associated with skin injuries. 相似文献