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21.
The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity 总被引:20,自引:6,他引:20
Hughes CM; Lewis SE; McKelvey-Martin VJ; Thompson W 《Human reproduction (Oxford, England)》1998,13(5):1240-1247
The integrity of sperm DNA is crucial for the maintenance of genetic
health. A major source of damage is reactive oxygen species (ROS)
generation; therefore, antioxidants may afford protection to sperm DNA. The
objectives of the study were, first, to measure the effects of antioxidant
supplementation in vitro on endogenous DNA damage in spermatozoa using the
single cell gel electrophoresis (comet) assay and, second, to assess the
effect of antioxidant supplementation given prior to X-ray irradiation on
induced DNA damage. Spermatozoa from 150 patients were prepared by Percoll
centrifugation in the presence of ascorbic acid (300, 600 microM), alpha
tocopherol (30, 60 microM), urate (200, 400 microM), or acetyl cysteine (5,
10 microM). DNA damage was induced by 30 Gy X-irradiation. DNA strand
breakage was measured using the comet assay. Sperm DNA was protected from
DNA damage by ascorbic acid (600 microM), alpha tocopherol (30 and 60
microM) and urate (400 microM). These antioxidants provided protection from
subsequent DNA damage by X-ray irradiation. In contrast, acetyl cysteine or
ascorbate and alpha tocopherol together induced further DNA damage.
Supplementation in vitro with the antioxidants ascorbate, urate and alpha
tocopherol separately has beneficial effects for sperm DNA integrity.
相似文献
22.
Permanent impairment of embryo development by hydrosalpinges 总被引:6,自引:9,他引:6
Recent reports suggest a deleterious effect of hydrosalpinges on pregnancy
outcome for in-vitro fertilization (IVF) and improvement following surgical
treatment. We compared the effect of hydrosalpinx on pregnancy outcome in
286 patients having 348 IVF cycles and followed the development of
untransferred embryos for 7 days to determine if hydrosalpinges affect
oocyte quality or embryo development. The delivery rate per retrieval was
significantly lower for patients with hydrosalpinx, but was restored by
surgical treatment to that of patients without hydrosalpinx. However, the
implantation rate per embryo transferred and normal blastulation of
untransferred embryos, which were significantly decreased in patients with
hydrosalpinx, and growth arrest and degeneration of untransferred embryos,
which were significantly increased compared to patients without
hydrosalpinx, were not restored by surgical treatment of hydrosalpinges. We
conclude that surgical treatment of hydrosalpinges decreases early
pregnancy loss and improves pregnancy outcome, possibly by diminishing
reversible deleterious effects exerted on the endometrium. As we have seen
in our laboratory, hydrosalpinges may have a permanent negative influence
on ovarian function, follicular development and oocyte quality since
implantation of transferred embryos and normal blastulation of
untransferred embryos remain low, and in-vitro growth arrest and
degeneration remain high despite surgical treatment of hydrosalpinges.
相似文献
23.
Astrid LA. Kuijpers Rolph Pfundt Patrick LJM Zeeuwen Henri OF. Molhuizen Edwin CM. Mariman Peter CM. van de Kerkhof Joost Schalkwijk 《Clinical genetics》1998,54(1):96-101
Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms. 相似文献
24.
Dal Zotto L; Quaderi NA; Elliott R; Lingerfelter PA; Carrel L; Valsecchi V; Montini E; Yen CH; Chapman V; Kalcheva I; Arrigo G; Zuffardi O; Thomas S; Willard HF; Ballabio A; Disteche CM; Rugarli EI 《Human molecular genetics》1998,7(3):489-499
We have recently reported isolation of the gene responsible for X- linked
Opitz G/BBB syndrome, a defect of midline development. MID1 is located on
the distal short arm of the human X chromosome (Xp22. 3) and encodes a
novel member of the B box family of zinc finger proteins. We have now
cloned the murine homolog of MID1 and performed preliminary expression
studies during development. Mid1 expression in undifferentiated cells in
the central nervous, gastrointestinal and urogenital systems suggests that
abnormal cell proliferation may underlie the defect in midline development
characteristic of Opitz syndrome. We have also found that Mid1 is located
within the mouse pseudoautosomal region (PAR) in Mus musculus , while it
seems to be X- specific in Mus spretus. Therefore, Mid1 is likely to be a
recent acquisition of the M. musculus PAR. Genetic and FISH analyses also
demonstrated a high frequency of unequal crossovers in the murine PAR,
creating spontaneous deletion/duplication events involving Mid1. These data
provide evidence for the first time that genetic instability of the PAR may
affect functionally important genes. In addition, we show that MID1 is the
first example of a gene subject to X-inactivation in man while escaping it
in mouse. These data contribute to a better understanding of the molecular
content and evolution of the rodent PAR.
相似文献
25.
26.
DL?MagerEmail author AD?Haffajee PM?Devlin CM?Norris MR?Posner JM?Goodson 《Journal of translational medicine》2005,3(1):27
Background
The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls. 相似文献27.
Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease 总被引:11,自引:4,他引:11
Cruts M; van Duijn CM; Backhovens H; Van den Broeck M; Wehnert A; Serneels S; Sherrington R; Hutton M; Hardy J; St George-Hyslop PH; Hofman A; Van Broeckhoven C 《Human molecular genetics》1998,7(1):43-51
Two closely related genes, the presenilins ( PS ), located at chromosomes
14q24.3 and 1q42.1, have been identified for autosomal dominant Alzheimer
disease (AD) with onset age below 65 years (presenile AD). We performed a
systematic mutation analysis of all coding and 5'-non-coding exons of PS -1
and PS -2 in a population-based epidemiological series of 101 unrelated
familial and sporadic presenile AD cases. The familial cases included 10
patients of autosomal dominant AD families sampled for linkage analysis
studies. In all patients mutations in the amyloid precursor protein gene (
APP ) had previously been excluded. Four different PS -1 missense mutations
were identified in six familial cases, two of which where autosomal
dominant cases. Three mutations resulted in onset ages above 55 years, with
one segregating in an autosomal dominant family with mean onset age 64
years (range 50-78 years). One PS -2 mutation was identified in a sporadic
case with onset age 62 years. Our mutation data provided estimates for PS
-1 and PS -2 mutation frequencies in presenile AD of 6 and 1% respectively.
When family history was accounted for mutation frequencies for PS -1 were
9% in familial cases and 18% in autosomal dominant cases. Further,
polymorphisms were detected in the promoter and the 5'-non-coding region of
PS -1 and in intronic and exonic sequences of PS -2 that will be useful in
genetic association studies.
相似文献
28.
L Ozzello CM De Rosa EW Blank K Cantell RL Ceriani DV Habif Sr 《Breast cancer research and treatment》1993,25(3):265-276
Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of125I-nIFN/Mc5 by the tumors was greater and its elimination slower than for125I-nIFN alone or conjugated to irrelevant mouse IgG1. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy. 相似文献
29.
To find out the efficacy of sucralfate in preventing gastrointestinal side effects of non-steroidal anti-inflammatory drugs (NSAIDs) a prospective, randomised single blind study was conducted from 1989 to 1992. Patients with osteoarthritis, rheumatoid arthritis and other long standing painful conditions, who were expected to receive NSAIDs for over three months, were recruited into the study. All medicines were discontinued for a period of 10–15 days prior to initial endoscopic assessment. NSAID therapy was started and the patients were randomised to receive either placebo (group A) or sucralfate (group B) in addition. Patient were reassessed clinically every week and an endoscopic examination was repeated after 6–8 weeks of follow-up. A total of 176 patients were studied in group A (n=91) and group B (n=85). At the end of 8 weeks gastrointestinal symptoms were present in 30.6% and 26.4% patients of group A and B respectively. Endoscopic assessment showed superficial lesions in 36.5% and 18.7% while endoscopic ulcer in 2.4% and 1.1% patients of groups A and B respectively. Thus in patients receiving chronic NSAID therapy, simultaneous administration of sucralfate reduces the incidence of superficial gastric lesions but has no significant effect on symptoms or ulcer formation.KEY WORDS: Gastropathy, Sucralfate, Nonsteroidal anti-inflammatory drugs 相似文献
30.
Robert Maggisano MD Avery Nathens MD Natalia A. Alexandrova MD Claudio Cina MD Bernard Boulanger MD Robert McKenzie MD Allan W. Harrison MD 《Annals of vascular surgery》1995,9(1):44-52
Although the traditional therapy for blunt traumatic rupture of the thoracic aorta (TRA) is immediate operative repair, there may be a selective role for delayed repair, particularly in patients with head trauma, respiratory failure, or cardiac dysfunction. The present study examines the hypothesis that TRA can be managed by selective delayed operative repair. Clinical data were collected from 59 consecutive patients with TRA at a regional trauma unit. All TRAs were at the aortic isthmus. Patients were retrospectively classified into three groups: group I (n=12) included patients who either arrived in extremis or rapidly became unstable during triage; group II (n=3) included patients who had no contraindications to early repair and underwent repair at the time of diagnosis; and group III (n=44) consisted of patients who because of concomitant injuries or sepsis required initial admission and management in the intensive care unit until their clinical status had improved sufficiently to allow for deliberate delayed operative repair of the TRA. The delay ranged from 1 day to 7 months. Eight patients have yet to undergo repair and remain well at follow-up from 1 to 4 years. Overall survival rates in groups I, II, and III were 17%, 100%, and 82%, respectively. The surgery-related mortality rate in group III was 10% (three patients). Only two (4.5%) patients in group III died as a result of a ruptured aorta within 72 hours of admission. In conclusion, contrary to surgical doctrine, TRA may not require immediate operative repair in all cases, but may instead be managed selectively depending on the patient's clinical status. 相似文献