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Genetic studies have provided evidence for an autism susceptibility locus (AUTS1) on chromosome 7q. Screening for mutations in six genes mapping to 7q, CUTL1, SRPK2, SYPL, LAMB1, NRCAM and PTPRZ1 in 48 unrelated individuals with autism led to the identification of several new coding variants in the genes CUTL1, LAMB1 and PTPRZ1. Analysis of genetic variants provided evidence for association with autism for one of the new missense changes identified in LAMB1; this effect was stronger in a subgroup of affected male sibling pair families, implying a possible specific sex-related effect for this variant. Association was also detected for several polymorphisms in the promoter and untranslated region of NRCAM, suggesting that alterations in expression of this gene may be linked to autism susceptibility.

Udgivelsesdato: 1994-Sep OBJECTIVE: To examine the effects of two proteoglycans of different structure, isolated from human follicular fluid (FF), on the motility of human spermatozoa. DESIGN: Normozoospermic semen samples and their swim-up sperm fractions were incubated in the presence of 0.4 mg/mL of a larger chondroitin sulfate proteoglycan (CS-PG) for 0, 3, 7, and 16 hours. The effects of a smaller heparan-CS-PG and the chondroitin sulfate side chains of the larger proteoglycan were also investigated in the same conditions. Sperm motility parameters were analyzed using a computer-aided sperm analysis system (CASA; Cryo Research Inc., New York, NY) RESULTS: The larger CS-PG caused an immediate increase in sperm linearity. After 3 and 7 hours, the retention of sperm motility, velocity, linearity, and amplitude of lateral head displacement have increased by an average of 13% compared with the control samples. After a 16-hour incubation, the retention of the motility properties was improved by approximately 40% (range, 27% to 50%) in the samples containing proteoglycan. The effects of the isolated glycosaminoglycan side chains were much lower than those of the intact proteoglycan. The heparan-CS-PG did not affect sperm motility. CONCLUSION: A CS-PG from FF increases retention of motility and velocity of human sperm. These physiological effects may enhance the fertilizing efficiency of spermatozoa in the female reproductive tract.

The course of delivery in 1,545 primiparae who were considered to be in the low-risk group at the commencement of labour as assessed by the previous directives issued by the Danish Ministry of Health (1976) were reviewed. 2/3 were delivered normally as episiotomy was not regarded as a complication. 1/3 had complicated deliveries. In 350, the contractions were abnormal and intervention was required. 1/3 of these were delivered instrumentally. Haemorrhage of more than 500 ml, intrauterine asphyxia and Apgar score less than or equal to 7 at 1 minute occurred frequently in this group. A total of 1,195 did not receive treatment to improve contractions and, in this group, instrumental delivery was undertaken in 10%. Following normal labour pains and spontaneous delivery, complications in the third stage were observed in 77 out of 1,075 patients, including haemorrhage of more than 500 ml in 38 patients. Six infants in this group had Apgar scores less than or equal to 7 at 5 minutes. In the group with abnormal contractions and/or instrumental delivery, haemorrhage of more than 500 ml, retention of the placenta and signs of perinatal asphyxia occurred, however, significantly more frequently. The authors consider that home deliveries in primiparae cannot be recommended. Primiparae should be advised to be delivered in hospital as it is not always possible to predict complications.

Udgivelsesdato: 1999-Jun-15 Two proteoglycans differing in size and composition were isolated from human follicular fluid. The larger one of high density had a molecular mass of 3.0x10(6) Da, as determined by laser light-scattering, and was substituted with 15-20 chondroitin sulphate (CS) chains (Mr 60000-65000). Half of the CS disaccharides were 6-sulphated, whereas the remaining ones were non-sulphated. Digestion of the CS proteoglycan with chondroitinase ABC lyase, followed by SDS/PAGE, yielded a protein core of 600 to 700 kDa including substituted oligosaccharides, and a band of 70 kDa that was identified as the heavy-chain component of the inter-alpha-trypsin inhibitor (ITI). Western blotting of the CS proteoglycan showed that this had reactivity with antibodies raised against human versican. Electron microscopy (EM) of the CS proteoglycan also revealed a versican-like structure, with one globular domain at each end of a long extended segment substituted with CS side chains, as well as a structure interpreted as being the heavy chain of ITI attached to CS chains. Laser light-scattering revealed that the smaller proteoglycan had a molecular mass of 1. 1x10(6) Da, and EM demonstrated that it had a globular-protein core structure. The core protein, which showed immunological reactivity with perlecan antibodies, was substituted with approximately seven heparan sulphate (HS) and CS chains of similar size (50-55 kDa), the CS disaccharides being mainly 6-sulphated (68%), with a small proportion being 4-sulphated. The protein core was shown to be heterogeneous, with bands occurring at 215, 330 and 400 kDa after enzymic degradation of the glycosaminoglycan chains followed by SDS/PAGE analysis. The demonstration of intact molecules and fragments obtained after stepwise degradations, as shown by gel chromatography, supported a 'composite' structure of this proteoglycan.