Apparent Sotos syndrome (cerebral gigantism) in a child with trisomy 20p11.2‐p12.1 mosaicism

We report on a child with apparent Sotos syndrome (cerebral gigantism) and partial duplication of the short arm of chromosome 20 mosaicism. Trisomy 20p11.2‐p12.1 was diagnosed using cytogenetic and FISH studies. The somatostatin receptor 4 (SSTR4) gene is included in the duplicated segment. This suggests that a dosage effect of this gene might be related to some of the clinical findings observed in our patient. The present observation emphasizes the importance of chromosome analysis in patients with well‐delineated but sporadic conditions. Am. J. Med. Genet. 91:273–276, 2000. © 2000 Wiley‐Liss, Inc.     

γ-Glutamyl transpeptidase-dependent mutagenicity and cytotoxicity of γ-glutamyl derivatives: A model for biochemical targeting of chemotherapeutic agents

Many carcinomas in humans are rich in γ-glutamyl transpeptidase (GGT), a plasma membrane enzyme that reacts with extracellular substrates. Thus, biochemical targeting of chemotherapeutic agents may be achieved by converting anticancer drugs into their γ-glutamyl derivatives. Chemical conversion of phenylhydrazine (PH) and biochemical modification of daunomycin (DM) into their γ-glutamyl derivatives γ-glutamyl phenylhydrazine (GGPH) and γ-glutamyl DM (GGDM) resulted in the abolishment of their mutagenicity and cytotoxicity, as judged by decreased viability and increased mutant yields in cultures of several Salmonella Ames strains. Commercial γ-glutamyl-p-nitroanilide (GGPNA) was not toxic or mutagenic. Mutagenicity and/or cytotoxicity of these γ-glutamyl derivatives were restored upon reaction with GGT, with concomitant release of PH, and p-nitroaniline (PNA). The GGT-dependent release of DM from GGDM was demonstrated by thin layer chromatography (TLC), spectral analysis, and specific mutagenicity. Mutagenicity and/or cytotoxicity of γ-glutamyl derivatives increased in the presence of glycylglycine, a GGT activator, and decreased in the presence of serine-borate, a GGT inhibitor. GGDM retained considerable DNA binding capacity. Its inability to kill and mutagenize was due to altered transport properties. The results are compatible with the notion that γ-glutamylation is a feasible method for biochemical targeting of drugs containing a primary amino group to GGT-rich tumors. Environ. Mol. Mutagen. 32:377–386, 1998 © 1998 Wiley-Liss, Inc.     

Prenatal sonographic appearance of congenital fibrosarcoma

Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the 22nd week of her first pregnancy underwent sonographic examination, which revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was terminated, and congenital fibrosarcoma was diagnosed by pathologic examination. To our knowledge, this is the first published report of the intrauterine sonographic observation of this tumor in a fetal extremity. © 1998 John Wiley & Sons, Inc. J Clin Ultrasound 26:276–279, 1998.     

Promotion of glutathione-γ-glutamyl transpeptidase-dependent lipid peroxidation by copper and ceruloplasmin: The requirement for iron and the effects of antioxidants and antioxidant enzymes

Oxidative damage (lipid peroxidation, LPO) induced in a completely defined system containing glutathione (GSH), purified γ-glutamyl transpeptidase (GGT), and EDTA- and ADP-chelated ferric iron was enhanced by catalytic amounts of cupric ions and by ceruloplasmin (CP). The enhancement depended on GSH concentration, GGT activity, the presence of iron, and the chelation of copper by ophenanthroline. High concentrations of CP inhibited LPO. Cu- and CP-enhanced, GSH-GGT-driven LPO was inhibited by the chain-breaking radical scavengers butylated hydroxyanisol, α-tocopherol, and Trolox C (a synthetic analog of α-tocopherol) but not by the hydroxyl scavenger mannitol. Ascorbic acid increased LPO in the presence of Cu or CP. Cu-enhanced LPO was partially sensitive to superoxide dismutase but not to catalase or horseradish peroxidase. The results indicate that Cu and CP enhance thiol-driven LPO and promote thiol-dependent mutagenesis by a very similar, if not the same, mechanism and are in agreement with the idea that this enhancement is due to redox reactions of chelated Cu and Fe, rather than to the reactivity of Cu in the Fenton reaction. Environ. Mol. Mutagen. 29:73–80, 1997 © 1997 Wiley-Liss, Inc.     

Sickle cell disorder, β-globin gene cluster haplotypes and α-thalassemia in neonates and adults from Guadeloupe

We have studied haplotype of β^s chromosome and α-globin gene status in 534 patients (255 adults and 279 children of whom 159 neonates) from Guadeloupe with various sickle cell-related conditions, namely SS (n = 298), SC (n = 170), S-β -thal (n = 56), and other rare forms (n = 10). Haplotype data on β^s chromosomes confirm our previous observation that Benin type is the most prevalent (75%) β^s chromosome in Guadeloupe, in disagreement with the historical records. Comparison of the frequency of distribution of various β^s haplotypes between neonates and adults on the one hand and between SS and SC cases on the other shows that the current β^s haplotype distribution in this island is not distorted by haplotype-related differential survival. We also show that the frequency of α-thalassemia (-3.7 kb) in Guadeloupe is one of the highest recorded in this region involved in Atlantic slave trade and also failed to reveal any age-dependent increase in frequency. We conclude that the African component of Guadeloupe is distinct from that of Brazil and Cuba but is close to that of Jamaica. Am. J. Hematol. 55:24-27, 1997. © 1997 Wiley-Liss, Inc.     

Genetic basis of the polymorphisms of the αI domain of spectrin

Defects of α spectrin have been identified in many cases of hereditary elliptocytosis (HE) and hereditary pyropoikilocytosis (HPP). To aid in the genetic analysis of families with these disorders, the locations of three α-spectrin gene polymorphisms were mapped, the genetic basis of these polymorphisms identified, and PCR-based assays designed for their identification. The frequencies of these polymorphisms were determined in two populations and in patients with αI/50a HE and HPP. These studies identified two distinct haplotypes and provided evidence that two HE/HPP mutations associated with the αI/50a protein phenotype, L207P and L260P, arose on separate chromosomal backgrounds. Am. J. Hematol. 56:107–111, 1997. © 1997 Wiley-Liss, Inc.     

Molecular detection using aptamer-modified gold nanoparticles with an immobilized DNA brush for the prevention of non-specific aggregation

Gold nanoparticles (AuNPs) are often used for biosensing. In particular, aptamer-modified AuNPs are often used for colorimetric molecular detection, where target molecule-induced AuNP aggregates can be recognized by a color change from red to blue. However, non-specific aggregation could be induced by various compounds, leading to false-positive results. In this work we employed high-density ssDNA modification on the AuNP surface to prevent non-specific aggregation. The covalently immobilized DNA brush was used as an anchor for an aptamer specific for the target molecule. Herein, as a proof-of-concept study, we demonstrated detection of estradiol (E2), one of the endocrine-disrupting estrogen molecules as a model target, in the presence of antibiotic kanamycin (KN) as a model of co-contaminating compounds that induce non-specific aggregation of AuNPs. We also developed a smartphone dark field microscope (DFM) to visualize AuNP aggregation. Our previous study demonstrated that the observation of light scattering by AuNP aggregates with DFM can be applied for versatile molecular detection. In this work, we could successfully detect E2 with the smartphone DFM, and the results were verified by the results from a conventional benchtop DFM. This study would contribute to the future field applicability of AuNP-based sensors.

We demonstrated molecular detection using aptamer-modified gold nanoparticles with DNA-brush for the prevention of non-specific aggregation and smartphone darkfield microscopy.     

Telomere elongation via alternative lengthening of telomeres (ALT) and telomerase activation in primary metastatic medulloblastoma of childhood

Journal of Neuro-Oncology - Elongation of telomeres is necessary for tumor cell immortalization and senescence escape; neoplastic cells use to alternative pathways to elongate telomeres: telomerase...     

Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward‐driven behaviors, which can result in life‐altering morbidity. The mesocorticolimbic dopamine network guides reward‐motivated behavior; however, its role in this treatment‐related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward‐learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD‐fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex‐matched PD patients with (n = 19) or without (n = 18) ICB. An incentive‐based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole‐brain voxelwise analyses and region‐of‐interest‐based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala‐to‐midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum‐to‐subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment‐avoidance learning. These data indicate that PD‐ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward‐based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509–521, 2018. © 2017 Wiley Periodicals, Inc.