Isokinetic knee joint test in "gonalgia sine materia"

Fifty-four subjects, aged between 20 and 35 years, divided into two subgroups, respectively 30 healthy subjects (17 males and 13 females) and 24 subjects with "gonalgia sine materia" (13 males and 11 females) underwent isokinetic exercise test in order to compare their dominant limb with the not dominant one as regard as the strength of extensor and flexor muscles of the knee. No statistically significant difference was found in any of the studied parameters in the comparison between the dominant limb and the not dominant one, both within the subgroup of healthy subjects and within the subgroup of subjects with "gonalgia sine materia". Authors conclude that psychological features may play a preeminent role in the genesis, as well as in the maintenance of "gonalgia sine materia", thus confirming previous data available in medical literature.     

Corpus callosum agenesis, multiple cysts, skin defects, and subtle ocular abnormalities with a de novo mutation [45,XX,der(5), t(5;;14) (pter;q11.2)

We report on a 2-year-old girl with a de novo mutation [45,XX,der(5),t(5;14) (pter;q11.2)] with corpus callosum agenesis, multiple cysts (cerebral and cardiac), subtle eye abnormalities, and at least two different skin defects, strongly indicating neuroectodermal involvement, as a neuromuscular choristoma (hamartoma) and an eccrine hamartoma. Fluorescent in situ hybridization with different single-locus probes showed that chromosome 5 has a very small deletion, confined to a region composed of repetitive sequences. By contrast, the long (q) arm of chromosome 14 seems to be much more involved in the rearrangement, with partial monosomy spanning from the centromere to the D14S72 and D14S261 loci. The extent of the deleted region of chromosome 14 is approximately 16 cM. To our knowledge, this is the smallest reported deletion involving the chromosome 14q11.2 region to be associated with a developmental disorder resulting in variable eye, skin, and brain anomalies. We suggest that a new syndrome, mimicking in some ways the MLS phenotype, is caused by a deletion in the chromosome 14q11.2 region.     

Is fecundability associated with month of birth? An analysis of 19th and early 20th century family reconstitution data from The Netherlands

The relationship between fecundability and month of birth was investigated in a cohort of 1526 women who married between 1802 and 1929, using only women whose first marriage occurred before the age of 35 years. On the basis of their time to pregnancy (TTP, calculated as time between wedding and first birth minus gestational length), women were categorized into two groups: fecunds (TTP up to 12 months or prenuptial conceptions, n = 1348) and subfecunds (TTP >18 months, n = 118). By use of logistic regression, cosinor functions with a period of 1 year or 6 months and variable shift and amplitude were fitted through the monthly odds of subfecunds versus fecunds. The best fitting curve was unimodal, with a zenith in September (P = 0.13 for H0: no differences). Exclusion of childless women (n = 36, minimum follow-up 5 years) from the subfecunds led to a similar curve (P < 0.01), while childless women, as compared with fecunds, showed a birth distribution that was best represented with a bimodal curve with zeniths in January and July (P = 0.06). This study provides evidence for the existence of differences in fecundability by month of birth. The cause of this relationship is unclear, but may lie in a melatonin-dependent circannual variability of the quality of the oocyte.      

Histone deposition protein Asf1 maintains DNA replisome integrity and interacts with replication factor C

Chromatin assembly and DNA replication are temporally coupled, and DNA replication in the absence of histone synthesis causes inviability. Here we demonstrate that chromatin assembly factor Asf1 also affects DNA replication. In budding yeast cells lacking Asf1, the amounts of several DNA replication proteins, including replication factor C (RFC), proliferating cell nuclear antigen (PCNA), and DNA polymerase epsilon (Pol epsilon), are reduced at stalled replication forks. In contrast, DNA polymerase alpha (Pol alpha) accumulates to higher than normal levels at stalled forks in asf1Delta cells. Using purified, recombinant proteins, we demonstrate that RFC directly binds Asf1 and can recruit Asf1 to DNA molecules in vitro. We conclude that histone chaperone protein Asf1 maintains a subset of replication elongation factors at stalled replication forks and directly interacts with the replication machinery.     

Genetic instability in superficial bladder cancer and adjacent mucosa: an interphase cytogenetic study

A systematic analysis of both tumors and the surrounding urothelium to help identify what lies behind the mechanism of multifocal tumor development has not yet been performed. In this study we investigated chromosome 1, 7, 9, and 17 aneusomy in 25 superficial papillary carcinomas and in 51 tissue samples taken from sites of macroscopically uninvolved urothelium surrounding the tumors, using the fluorescence in situ hybridization method. Our data demonstrated a close genetic relationship between all examined tumors and normal-appearing mucosa. Numeric aberrations of chromosomes 1, 7, 9, and 17 were found to exhibit similar patterns in all analyzed specimens, although with different frequencies.     

Erratum: Neurofibromatosis type 1 (NF1): Identification of eight unreported mutations in NF1 gene in Italian patients

In the original version of this article, the title was incorrect. Please find the correct title given here. The publisher deeply regrets this error. The original article to which this Erratum refers was published in Human Mutation 22:179–180 Human Mutation(2003) 22(2) 179–180     

Mechanisms of the ATP potentiation of hyposmotic taurine release in Swiss 3T3 fibroblasts

Reducing osmolarity by 35% increased ³H-taurine efflux from Swiss 3T3 fibroblasts from 0.5% to a peak of 5.7%. The presence of ATP (10–100 µM; EC₅₀ 1.5 µM) increased taurine efflux up to 10%, and decreased the set point for hyposmotically stimulated taurine release (HTR). ATP potentiation was mimicked by UTP, reduced by addition of suramin and pyridoxal phosphate-6-azophenyl-2,4-disulphonic acid (PPADS) and unaffected by ADP, ,-methylene-ATP (,-ATP) or 2-methylthio-ATP (Me-ATP), suggesting its mediation by purinergic P2Y₂ and P2Y₄ metabotropic receptors. Under isosmotic conditions ATP increased the cytosolic [Ca²⁺] ([Ca²⁺]_i) markedly, but did not increase taurine release. HTR was independent of external Ca²⁺ but was reduced (by 56–59%) by BAPTA-AM, thapsigargin-induced depletion of intracellular Ca²⁺ stores, or phospholipase C (PLC) inhibition. Blockade of calmodulin (CaM) or calmodulin kinase II (CaMKII) reduced HTR by 54% and 76%, respectively. The ATP-mediated potentiation was prevented fully by all these treatments. HTR was reduced by 30–50% by blockers of protein tyrosine kinases (AG18), phosphoinositide 3-kinase (PI3K) (wortmannin), p21rho (toxin B), p21rho-kinase (Y27632) and the stress-activated kinase p38 (PD169316). ATP-mediated potentiation was reduced similarly by these blockers. Simultaneous inhibition of PI3K and CaMKII abolished HTR. Altogether, these results suggest a modulatory effect of ATP, probably exerted by a potentiation of the Ca²⁺-dependent fraction of HTR. This fraction has as signalling elements a PLC-dependent [Ca²⁺]_i increase, resulting from Ca²⁺ released from thapsigargin-sensitive internal stores, followed by activation of CaM/CaMKII reactions. The Ca²⁺/ATP effect operates only when the Ca²⁺-independent, tyrosine kinase-mediated pathway is already activated. Suggested elements of cross-talk between the two pathways are PLC, PI3K and CaMKII.     

Large deletions of the MECP2 gene detected by gene dosage analysis in patients with Rett syndrome

The original article to which this Erratum refers was published in Human Mutation 23:234–244 Human Mutation(2004) 23(3) 234–244