A case of Alagille's syndrome with translocation (4;14) (q21;q21)

This paper reports a case of Alagille's syndrome, in association with a translocation 46,XY,t(4;14)(q21;21). The possible relationship between this autosomal dominant syndrome and the apparently balanced chromosomal rearrangement is discussed.     

Characterization of Nine Novel Mutations in the CD40 Ligand Gene in Patients with X-Linked Hyper IgM Syndrome of Various Ancestry

X-linked immunodeficiency with hyper-IgM (HIGMX-1) is a rare disorder caused by defective expression of the CD40 ligand (CD40L) by activated T lymphocytes, resulting in inefficient T-B cell cooperation and failure of B cells to undergo immunoglobulin isotype switch. In the present work, we describe nine patients of various ancestry who bear different mutations in the X chromosome–specific CD40L gene. Two of the mutations were nonsense mutations, one each resulting in premature stop codons at amino acid residues 39 and 140. Three patients had single point missense mutations, one each at codons 126, 140, and 144. Another patient had a 4-bp genomic deletion in exon 2, resulting in a frameshift and premature termination. Three patients showed insertions, one each of 1, 2, and 4 nt, probably because of polymerase slippage, resulting in frameshift mutation and premature termination. Overall, these observations confirm the heterogeneity of mutations in HIGMX-1. However, the identification of two patients whose mutation involves codon 140 (previously shown to be altered in two other unrelated subjects) suggests that this may be a hotspot of mutation in HIGMX-1. In two additional patients with clinical and immunological features indistinguishable from canonical HIGMX-1, no mutation was detected in the coding sequence, in the 5' flanking region, or in the 3' UTR.     

A hormone-dependent post-translationally regulated mutant for investigating type I cadherin function.

Type I cadherins are Ca2+-dependent cell adhesion molecules. Their function in early Xenopus laevis development has been extensively studied in recent years, by injecting synthetic mRNAs encoding dominant negative mutants with deletions of the extracellular domain into embryos. However, studies at post-gastrula stages have been hampered by the inabilityto progress through post-gastrula development in embryos expressing these mutant proteins. This problem has been partly overcome by injecting into a few targeted blastomeres in stage 6 N.F. embryos, but only restricted studies are possible with this technique. Several studies have made use of the hormone-binding domain (HBD), which is activated by hormones. In this study, we used this method to analyze the activity of dominant negative cadherins. We generated a mutant E-cadherin (AE-Cad, consisting of the cytoplasmic domain and transmembrane domain) fused to the hormone-binding domain of estradiol receptor (HBDER) and we validated this technique with functional analyses. The function of the mutant deltaE-HBDER was strictly dependent on hormone induction. This conditional mutant had the same effects and exerted the same dominant negative function as the corresponding constitutive mutant.     

Resource density regulates the foraging investment in higher termite species

1. Resource density can regulate the area that animals use. At low resource density, there is a conflict in terms of balance between costs of foraging and benefits acquired. The foraging of the higher termite Nasutitermes aff. coxipoensis consists of searching throughout trails and a building galleries phase. 2. In this study, a manipulative field experiment was used to test the hypothesis that colonies of N. aff. coxipoensis forage towards a more profitable balance between the establishment of trails and gallery construction at low resource density. 3. The experiment was conducted in north‐eastern Brazil. Seven experimental plots were established with a continuous increase in resource density (sugarcane baits). Entire colonies of N. aff. coxipoensis were transplanted from their original sites to the experimental plot, totalling 35 nests. The number, branches and total length of trails and galleries were quantified. 4. The results show that N. aff. coxipoensis optimises its foraging output, intensifying the establishment of trails at the cost of gallery construction when resource density is low. The number of trails, the number of trail branches and the total length of trails decreased with increasing resource density. Interestingly, at low resource density, the search effort was concentrated on forming longer and a greater number of trails, a small proportion of which were converted into galleries. The opposite relationship was observed at high resource density. 5. These results suggest an optimisation of search efforts during foraging depending on resource density, a mechanism that may help researchers to understand the use of space by higher termite species.     

Inhibition of testosterone-induced sexual behavior in the castrated male rat by aromatase blockers

The effect of some aromatase inhibitors (aminoglutethimide, 1,4,6-androstatrien-3, 17-dione, and 4-hydroxy-androstenedione) on testosterone propionate (TP)-induced copulatory behavior was tested in sexually inexperienced castrated male rats. A single injection of 6 mg of TP induced mounting in 48% and ejaculatory pattern in 19% of the rats within 120 hr. Treatment with the aromatase inhibitors (injections every 12 hr for 108 hr) suppressed ejaculation in all but one rat and significantly reduced the number of rats mounting and intromitting. Concurrent administration of estradiol benzoate (EB, 1 or 3 μg every 12 hr) prevented the inhibitory effect of aromatase blockers. No inhibitory effect of the aromatization blockers was observed in rats in which sexual behavior was induced by dihydrotestosterone (1 mg/day) and EB (2.5 μg/day) for 20 days. The results support the concept that aromatization is an essential step for the induction of male sexual behavior by androgen in the rat.     

Characteristics and management of congenital esophageal stenosis: findings from a multicenter study

Background

Congenital esophageal stenosis (CES) is a rare condition frequently associated with esophageal atresia (EA). There are limited data from small series about the presentation, treatment, and outcomes of CES.

Methods

Medical records of all patients with CES included in the French Network on Esophageal Malformations and Congenital Diseases were reviewed retrospectively with regard to diagnosis, treatment, and outcome.

Results

Over 18 years, 61 patients (30 boys) had CES, and 29 (47%) of these patients also had EA. The mean age at diagnosis was 24 months (1 day to 14 years) and was younger in patients with CES and EA than in those with isolated CES (7 vs. 126 months, p?<?0.05). Twenty-one of the 61 patients with CES had no clinical symptoms: in three patients, the findings were incidental, and in 18 of the 29 patients with associated EA, CES was diagnosed at the time of surgical repair of EA or during a postoperative systematic esophageal barium study. In the 40 other patients, at diagnosis, 50% presented with dysphasia, 40% with vomiting, 50% with food impaction, and 42% with respiratory symptoms. Diagnosis of CES was confirmed by esophageal barium study (56/61) and/or esophageal endoscopy (50/61). Sixteen patients had tracheobronchial remnants (TBR), 40 had fibromuscular stenosis (FMS), and five had membrane stenosis (MS). Thirty-four patients (56%) were treated by dilation only (13/34 remained asymptomatic at follow-up); 15 patients were treated by dilation but required later surgery because of failure (4/15 remained asymptomatic at follow-up); and nine patients had a primary surgical intervention (4/9 were asymptomatic at follow-up). Dilation was complicated by esophageal perforation in two patients (3.4%). At follow-up, dysphagia remained in 36% (21/58) of patients, but the incidence did not differ between the EA and the isolated CS groups (10/29 vs. 7/32, p?=?0.27).

Conclusions

CS diagnosis can be delayed when associated with EA. Dilation may be effective for treating patients with FMS and MS, but surgical repair is often required for those with TBR. Our results show clearly that, regardless of the therapeutic option, dysphagia occurs frequently, and patients with CES should be followed over the long term.

     

Characteristics of the motor and genital copulatory responses of the male hamster

The temporal and dynamic characteristics (duration, frequency, rhythmicity, and vigor) of pelvic thrusting displayed by 17 male golden hamsters during their copulatory behavioral responses: mounts, intromissions, ejaculations, and long intromissions, as well as their temporal correlation with the genital contacts established by intravaginal penile insertion, were studied by an accelerometric and polygraphic technique. Pelvic thrusting in all copulatory behavioral responses appeared as series or trains of rhythmical, synchronic, vigorous movements. The various pelvic thrusting trains lasted around 1 s on average, but those of mounts were significantly longer than the trains displayed in the other behavioral responses. The frequencies of pelvic thrusting were similar in all responses (around 15 thrusts per s) excepting mounts which had lower values. In intromission, ejaculation, and long intromission responses, when penile insertion occurred, pelvic thrusting either was interrupted or showed changes in its characteristics: penile insertion was related to a period without thrusting in intromissions, to a series of intravaginal thrusting of higher frequency (16.4 thrusts per s) and lower vigor in ejaculations, and to a prolonged period of 6 to 25 s of slow intravaginal pelvic thrusting (1–2 thrusts per s) in long intromissions. Penile insertion lasted longer in ejaculations than in intromissions and it was significantly shorter in both of these responses than in long intromissions. These results provide information about some dynamic aspects of sexual behavior in hamsters, as well as a temporal correlation between the motor and genital components of this behavior.