Blood pressure and cardiovascular involvement in children with neurofibromatosis type1

We evaluated blood pressure in a sample of patients with neurofibromatosis type 1 (NF1), using ambulatory blood pressure monitoring (ABPM), to determine whether ABPM, when compared with casual BP recordings, allowed the detection of a higher risk for hypertension. We also evaluated the correlation between BP and vascular abnormalities. We studied 69 NF1 patients (36 males and 33 females) with a mean age of 11±4 years, divided into group A, with 24-h mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) <95th percentile, and group B, with mean SBP or DBP >95th percentile. Standard electrocardiography and M-mode, two-dimensional echocardiography were performed and all patients were in sinus rhythm. ABPM identified 11 hypertensive patients (16%); 5 had a mean SBP >95th percentile, 3 mean SBP–DBP >95th percentile, and 3 a mean DBP >95th percentile. Laboratory and other investigations to exclude secondary hypertension were normal. Cardiac abnormalities were found in 13 of the 69 patients (18.8%) with NF1. There were no significant clinical and cardiac differences between the normotensive and hypertensive group. Our data emphasize the importance of periodic ABPM in NF1 patients to diagnose hypertension early and avoid target organ damage and increased mortality.     

Within-subject memory decline in middle-aged rats: effects of intraseptal tacrine

A longitudinal design was used to examine spatial working memory performance in aging Long-Evans rats on a 12-arm, delayed-non-match-to-sample radial maze task. Compared to performance at 12-13 months of age, the same rats exhibited a significant performance deficit at 15-16 months of age across all retention intervals (1.5-10h). All rats exhibited some degree of decline, and no rat performed as well as they had 3 months earlier. This early onset deficit may relate to the degree of difficulty required to perform accurately in a task that maximizes both spatial information processing and flexible working memory representations. Following our observation, rats were implanted with a chronic cannula aimed at the medial septal nucleus. Acute intraseptal tacrine treatments (0.0-25 micrograms/0.5 microl) did not significantly affect any index of performance. Rats exhibited further memory decline over the course of testing (up to 20 months of age). Detection of early onset dysfunction could allow for experimental analysis of underlying mechanisms and therapeutic strategies early in the course of age-related changes.     

CD38 low IgG-secreting cells are precursors of various CD38 high-expressing plasma cell populations

Despite the important role immunoglobulin G (IgG)-secreting plasma cells play in memory immune responses, the differentiation and homeostasis of these cells are not completely understood. Here, we studied the differentiation of human IgG-secreting cells ex vivo and in vitro, identifying these cells by the cellular affinity matrix technology. Several subpopulations of IgG-secreting cells were identified among the cells isolated from tonsils and bone marrow, particularly differing in the expression levels of CD9, CD19, and CD38. CD38 low IgG-secreting cells were present exclusively in the tonsils. A major fraction of these cells appeared to be early plasma cell precursors, as upon activation of B cells in vitro, IgG secretion preceded up-regulation of CD38, and on tonsillar sections, IgG-containing, CD38 low cells with a plasmacytoid phenotype were found in follicles, where plasma cell differentiation starts. A unitary phenotype of migratory peripheral blood IgG-secreting cells suggests that all bone marrow plasma cell populations share a common precursor cell. These data are compatible with a multistep model for plasma cell differentiation and imply that a common CD38 low IgG-secreting precursor gives rise to a diverse plasma cell compartment.     

Diabetes in an infant with cystic fibrosis

Cystic fibrosis (CF)-related diabetes mellitus is an unusual complication in very young pediatric patients with CF. It is generally associated with more severe clinical manifestations of CF. In this report, we describe a case of diabetes and CF starting in infancy. The patient manifested a form of intermittent diabetes without fasting hyperglycemia, which was exacerbated by steroid treatment during pulmonary disease and occasionally required insulin therapy. Insulin responses to oral and intravenous glucose challenge were low. The clinical and radiological status was stable during the 9-yr follow-up. Our patient demonstrates that diabetes may not only represent a complication of CF, as previously maintained, but can also be a co-morbid condition proceeding along with the exocrine disease. The early occurrence of hyperglycemia in this case may highlight an impairment of beta-cell function, which might be genetically determined. Careful monitoring of the glucose profile and of beta-cell function is indicated in patients with CF to avoid late recognition of diabetes.     

Hemolytic effects of water-soluble fullerene derivatives

A series of water-soluble fullerene C(60) derivatives has been investigated for their cytotoxic and hemolytic properties, with the aim to correlate structure with toxicity. We observed that cationic chains induce significant toxicity while the presence of neutral or anionic moieties did not produce any response in our model. A validation of these experimental observations has been performed by theoretical studies in which hydrophilic and hydrophobic surface areas were correlated quantitatively with hemolytic properties.     

Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas

Point mutations of the BRAF gene have been recently described with high prevalence in papillary thyroid carcinomas. However, this molecular alteration has not been studied in radiation-induced thyroid tumors. We analyzed the prevalence of BRAF point mutations and RET/PTC rearrangements in 55 post-Chernobyl papillary carcinomas, compared with 82 sporadic papillary carcinomas. Radiation-induced tumors demonstrated a low prevalence (4%) of BRAF point mutations and high prevalence (58%) of RET/PTC rearrangements. Sporadic papillary carcinomas revealed a clearly distinct pattern, with 37% of tumors harboring BRAF mutations and 20% RET/PTC rearrangements. These results demonstrate a significant difference in the molecular genetic profile of sporadic and radiation-induced thyroid tumors.     

Somatostatin in the brain of the cave salamander, Hydromantes genei (Amphibia, Plethodontidae): immunohistochemical localization and biochemical characterization

The distribution of somatostatin-like immunoreactivity in the brain of the cave salamander Hydromantes genei (Amphibia, Plethodontidae) was investigated by using two distinct antisera raised against somatostatin-14. Most somatostatin-positive cells were detected in the ependymal cell layer surrounding the ventricles. These cells possessed the typical morphological characteristics of tanycytes or radial glial cells. Double-labeling with an antiserum against somatostatin and a monoclonal antibody against glial fibrillary acidic protein showed that somatostatin-immunoreactive cells lining the ventricles also exhibited GFAP-like immunoreactivity. Injection of the neurotracer biocytin into the lateral ventricle revealed that neurons lining the ventricles did not contain somatostatin-like immunoreactivity. In the telencephalon, somatostatin-like immunoreactivity was confined to radial glial cells. In the diencephalon, in addition to somatostatin-immunoreactive cells in the ependyma, positive cell bodies were also found in the periventricular preoptic nucleus, the infundibular nucleus, the epiphysis, and the subcommissural organ. In the metencephalon, positive cell bodies were found in the auricula cerebelli, whereas in the rhombencephalon numerous somatostatin-immunoreactive cells were seen lining the ventricular cavity. Immunoreactive nerve fibers were observed in the hypothalamus-median eminence complex. In the pituitary, a discrete group of somatostatin-positive cells was found in the pars distalis. High-performance liquid chromatography analysis of brain extracts revealed that the immunoreactive material coeluted with somatostatin-14. The present results show that the somatostatin peptidergic system in the brain of the cave salamander has a more simple organization than those described in the brain of frog and other vertebrates. This feature is probably related to the expression of high pedomorphic characters in plethodontids. The distribution of somatostatin-like immunoreactivity suggests that, in the cave salamander, somatostatin may act as a neurotransmitter and/or neuromodulator, a central regulator of fluid homeostasis, and a hypophysiotropic neurohormone.     

Language switching mechanisms in simultaneous interpreters: an ERP study

Recent event-related potential (ERP) and neuroimaging studies suggest that bilingual individuals are able to inhibit the processing of a non-target language while speaking or reading in another language. The neural mechanisms subserving code switching still remain matter of debate. The aim of the present study was to shed some light on the neurofunctional bases of such mechanisms. ERPs were recorded in native Italian simultaneous interpreters and monolingual controls during a semantic processing task in which the subjects had to evaluate the sensibleness of final words of incomplete sentences. All participants were strictly right-handed. Interpreters knew at least four languages (from four to eight) at a professional level, from among 11 European and Asian languages, and had an excellent command of English (L2). Four hundred short sentences were presented visually; half of them had an unexpected final word, producing a semantic incongruence. Sentences could be entirely in Italian or in English (unmixed); alternatively, the body of the sentence could be in English and the final word in Italian or vice versa (mixed). ERPs were time locked to the onset of the final word. Both reaction times (RTs) and electrophysiological data indicated a lesser degree of hemispheric lateralization for linguistic function during L2 rather than L1 processing in interpreters. The first effect of lexical switching and code switching was recorded in the time window between 140 and 200 ms at left anterior sites. At N400 level, ERPs were significantly larger to L2 than to L1 words only in the mixed and not in the unmixed condition. No effect of language was observed in the unmixed condition, thus suggesting that the difference in L1/L2 processing was not related to a difference in proficiency, but rather to a different functional organization of semantic integration systems due to the later age of acquisition of L2 compared to L1. Interpreters were faster at reading and comprehending sentences in English ending with an Italian word than vice versa (L2 --> L1 switch).