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495.
Two male siblings from a consanguinous Pakistani family had fatal diarrhoea with an onset at 24 and 48 hours after birth. A diagnosis of microvillous inclusion disease (MVID) was established by showing characteristic light and electron microscopic features in the small intestinal biopsy specimen on day 6 of life in case 1. The typical abnormalities of MVID were also demonstrated retrospectively in case 2 by examining archival appendicular tissue from 10 years previously. These cases are consistent with an autosomal recessive inheritance for MVID. Retrospective diagnosis of MVID is possible by examining appropriate archival material, which may aid genetic counselling and future research. 相似文献
496.
Disturbances of growth and development in patients with thalassaemia receiving hypertransfusion programmes are well recognised and are most likely to be due to iron overload. The extent of endocrine dysfunction was investigated in a group of 18 patients thought to have been treated by acceptable modern standards, 11 of whom could be considered as well chelated. Assessment of growth and puberty showed a wide variation in height SD scores with five patients having significantly short stature. Most patients are progressing through puberty normally with the exception of two boys with marked pubertal delay. The most prominent finding was that growth hormone responses to glucagon stimulation were significantly impaired in all of the patients with iron overload. Basal endocrine assessment showed primary hypothyroidism in two patients aged 16.8 and 12.9 years with plasma thyroxine-concentrations of 86 and 59 nmol/l (normal range 65-165 nmol/l) and plasma thyroid stimulating hormone 10.2 and 30.3 mU/l (normal range 0.5-5 mU/l). One patient had diabetes mellitus. These results show that even when ideal management is sought a significant amount of endocrine damage occurs; surveillance of these patients is thus essential. 相似文献
497.
RD Milner KA Khallouf R Gibson A Hajianpour CG Mathew 《Archives of disease in childhood》1993,68(1):101-103
A family in which three siblings born to related parents all manifested clinical abnormalities characteristic of Fanconi's anaemia (microcephaly, short stature, slow growth, beak nose, micrognathia, skin dyspigmentation and forearm and thumb dysplasia in 2/3) is reported. All five family members had normal spontaneous chromosome breakage, a normal response to diepoxybutane and mitomycin C, and were fully informative for linkage with four DNA markers from chromosome 20q12-13.3 with no evidence for linkage. It is concluded that abnormalities typical for Fanconi's anaemia are inherited as an autosomal recessive without the defect responsible for increased chromosomal fragility and independently from the genes so far identified as being responsible for Fanconi's anaemia. 相似文献
498.
Choline deficiency selects for resistance to p53-independent apoptosis and causes tumorigenic transformation of rat hepatocytes 总被引:2,自引:1,他引:2
Zeisel SH; Albright CD; Shin OH; Mar MH; Salganik RI; da Costa KA 《Carcinogenesis》1997,18(4):731-738
The mechanisms which drive initiated cells to progress to form carcinomas
are poorly understood. CWSV-1 rat hepatocytes, in which p53 protein is
inactivated by SV40 large T antigen, respond by inducing p53- independent
apoptosis when acutely switched to medium containing low choline (16%
apoptotic at 48 h in 5 microM choline) as compared with controls (1%
apoptotic at 48 h in 70 microM choline). The rate of apoptosis was
inversely correlated with cellular phosphatidylcholine content. Choline
deficiency (CD)-induced apoptosis is probably mediated by TGFbeta1 and
reactive oxygen species, since immunoneutralization of TGFbeta1 in the
medium or treatment with N-acetylcysteine (an antioxidant) or addition of
neocuproine (a transition metal chelator) prevented CD-induced apoptosis.
CWSV-1 hepatocytes could be gradually adapted to survive in 5 microM
choline. CD-adapted cells had increased membrane phosphatidylcholine
concentrations (compared with acute CD cells). Adapted cells acquired
relative resistance to CD-induced apoptosis (7% of adapted cells compared
with 19% of non-adapted cells were apoptotic at 48 h in 5 microM choline).
They also became relatively resistant to another p53-independent form of
apoptosis (TGFbeta1-induced). CD-adapted hepatocytes developed increased
capability for anchorage-independent growth and formed tumors when
transplanted into nude mice; passage-matched control hepatocytes did not
possess these properties. Cell transformation was dependent on exposure to
the selective pressure of CD apoptosis, as we observed that when CD
apoptosis was inhibited with an antioxidant during adaptation, cells did
not become anchorage independent. Acquisition by p53- deficient cells of
resistance to p53-independent inducers of apoptosis (CD, TGFbeta1 and
reactive oxygen species) may leave cells without another important
apoptotic defensive barrier and may be responsible for the progression of
initiated cells to frank carcinomas.
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499.
ω-3多不饱和脂肪酸是一类具有生物活性的多不饱和脂肪酸,对结直肠癌发生发展具有抑制作用。ω-3多不
饱和脂肪酸首先改变膜流动性影响细胞功能,其次影响细胞信号转导通路中重要蛋白的活性并且调节肿瘤微环境中
炎症介质和免疫细胞的功能和活性,另外改变肿瘤转移过程中的几种重要分子,从抑制细胞过度增殖,促进凋亡,
提高抗肿瘤免疫和抑制肿瘤转移几个方面对结直肠癌起抑制作用。 相似文献
500.
Diet, caloric restriction, and the rodent bioassay 总被引:1,自引:1,他引:0
Keenan KP; Ballam GC; Soper KA; Laroque P; Coleman JB; Dixit R 《Toxicological sciences》1999,52(2):24-34
The diet can significantly alter the results of toxicity and
carcinogenicity studies. Ad libitum (AL) overfeeding of excessive calories
to sedentary adult rodents is one of the most poorly controlled variables
affecting the current rodent bioassay. AL-overfed rodents develop an early
onset of adverse metabolic events, endocrine- disruptive degenerative
diseases, and tumors that result in early morbidity and mortality. AL food
consumption is extremely variable, but has a strong correlation with adult
body weight, obesity, and survival. AL feeding of diets with modified
protein, fiber, and energy content are not as effective as simple, moderate
dietary (caloric) restriction (DR) in controlling these study variables.
Moderate DR (70-75% of adult AL) is operationally simple and controls adult
body weights, prevents obesity, and improves health and survival by
reducing or delaying diet- related endocrine, renal, and cardiac diseases.
Moderate DR provides a uniform rodent model, increases treatment exposure
time, and increases the statistical sensitivity of these chronic bioassays
to detect true treatment effects. Feeding a balanced diet by a moderate DR
regimen of 70-75% of the maximum, unrestricted adult AL food intake is
recommended for conducting well-controlled toxicity and carcinogenicity
studies.
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