Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

Functional consequences of ROMK mutants linked to antenatal Bartter's syndrome and implications for treatment

The antenatal variant of Bartter's syndrome is an autosomal recessive kidney disease characterized by polyhydramnios, premature delivery, hypokalemic alkalosis and hypercalciuria. It is genetically heterogeneous, having been linked recently to mutations in an ATP- sensitive, renal outer medullary K+channel, ROMK, and earlier to mutations in the Na-K-2Cl co-transporter, NKCC2. We characterized four of the mutations reported in three heterozygous ROMK variants of antenatal Bartter's and found that each expressed a distinct phenotype in Sf9 cells. One mutation expressed normal function and appears to be an allelic polymorphism. The other three mutations produced channels with significantly reduced K+fluxes. However, the mechanisms in each case were different and reflected abnormalities in phosphorylation, proteolytic processing or protein trafficking. The different mechanisms may be important in the design of appropriate therapy for patients with this disease.      

The influence of reported paternal attitudes on the decision to breast-feed

Objective: To identify factors that influence a woman's decision to breast-feed.
Methodology: Five hundred and fifty-six women were recruited from the maternity wards of two Perth hospitals. Data were collected from a self-administered questionnaire completed by participants prior to discharge. Logistic regression analysis was used to determine factors influencing the initiation of breast-feeding.
Results: At discharge from hospital 83.8% of women were breast-feeding, including 6% who were giving complementary formula feeds. After controlling for potentially confounding demographic and biomedical factors, the father's reported preference for breast-feeding was found to be the most important factor influencing a woman's decision to breast-feed (OR 10.18).
Conclusion: Fathers participate in and influence the choice of infant feeding method and should be included in breast-feeding discussions.     

Margin of safety for discharge after apnea in preterm infants

OBJECTIVE: Most neonatologists include an apnea-free period in the criteria for the discharge of preterm infants. However, the length of time one should wait after the cessation of apnea before sending an infant home without a monitor is debated. We undertook this study in an attempt to define a minimal and safe observation period between the time of the last apnea episode and discharge. METHODS: We reasoned that in infants with idiopathic apnea of prematurity, the intervals between days on which apnea occurs gradually increase until some point at which clinically significant apnea ceases. Therefore, knowledge about the intervals between days on which apnea occurred just before the last apnea would provide a reasonable estimate of the minimal safe observation interval between the last apnea and discharge. We reviewed the charts of 266 infants born in 1993 and 1994 at 相似文献   

Inhibition of cigarette smoke-related lipophilic DNA adducts in rat tissues by dietary oltipraz

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.      

Genitalverstümmelung und Strafrecht

Some of the girls who live in Germany and have Muslim parents are threatened by female genital mutilation. This report describes the kinds and medical consequences of female genital mutilation as well as the criminal judgement. Female genital mutilation is considered as dangerous bodily harm, not as grievous bodily harm. Consent does not justify the infringement of rights. The argument that Islam justifies the infringement of rights is irrelevant by law. The human right of bodily intactness has priority over the right of religious freedom. Finally the legal regulations about dealing with personal data are presented. A legal compulsory registration still does not exist.