Gastrointestinal disorders in Down syndrome

Down syndrome is the most common human chromosomal disorder. Among clinical findings, one constant concern is the high prevalence of gastrointestinal system alterations. The aim of this study was to determine the prevalence of gastrointestinal disorders at a Down syndrome outpatient clinic during a 10‐year follow‐up period. Data from medical files were retrospectively reviewed from 1,207 patients. Gastrointestinal changes occurred in 612 (50.7%). The most prevalent disorder was chronic intestinal constipation. Intestinal parasite occurred in 22% (mainly giardiasis), gastroesophageal reflux disease in 14%, digestive tract malformations occurred in 5%: 13 cases of duodenal atresia, 8 of imperforate anus, 4 annular pancreases, 2 congenital megacolon, 2 esophageal atresias, 2 esophageal compression by anomalous subclavian and 1 case of duodenal membrane. We had 38/1,207 (3.1%) patients with difficulty in sucking and only three with dysphagia that resolved before the second year of life. Peptic ulcer disease, celiac disease, and biliary lithiasis were less prevalent with 3% each. Awareness of the high prevalence of gastrointestinal disorders promotes outstanding clinical follow‐up as well as adequate development and greater quality of life for patients with Down syndrome and their families.     

CTLA-4 (CD152) gene polymorphism at position 49 in exon 1 in Graves' disease in a Polish population of the Lower Silesian region

INTRODUCTION: Graves' disease ((GD)is an autoimmune disease believed to be caused by a combination of environmental and genetic factors. The gene encoding cytotoxic T lymphocyte-associated antigen-4 (CTLA-4)is one of the candidate genes for conferring susceptibility to thyroid autoimmunity. he aim of the study was to investigate the association between the exon 1 CTLA-4 gene polymorphism A(49)G and susceptibility to GD and Graves ' ophthalmopathy (GO)as well as its severity in a Polish population of the Lower Silesia region. MATERIALS AND METHODS: We analyzed the A(49)G exon 1 CTLA-4 gene polymorphism in 99 unrelated Polish patients with GD, of whom 50 had clinically evident GO (NOSPECS class III and higher), and 154 matched healthy subjects from the Lower Silesia region. Genomic DNA was isolated from whole frozen blood using the NucleoSpin Blood kit. A/G transition was genotyped by polymerase chain reaction followed by labeling with the SnaPshot kit of PE Applied Biosystems and detected using an ABI PRISM 310 capillary genetic analyzer. RESULTS: The distribution of CTLA-4 exon 1 A(49)G enotype, allele, and phenotypic frequencies did not differ between patients with GD and healthy subjects. There was a significantly lower frequency of the AA genotype in the group of patients with clinically evident GO than in patients without severe GO (22% vs. 43%; p=0.02, OR=2.6). CONCLUSIONS: Our results showed that the AA genotype in patients with GD is associated with a lower risk of GO severity.     

PCR analysis of pulsed-field gel electrophoresis-purified plastid DNA,a sensitive tool to judge the hetero-/homoplastomic status of plastid transformants

The genetic transformation of plastids of higher plants has developed into a powerful approach for both basic research and biotechnology. Due to the high copy number of the plastid genome per plastid and per cell, repeated cycles of shoot regeneration under conditions selective for the modified plastid chromosome are required to obtain transformants entirely lacking wild-type plastid genomes. The presence of promiscuous plastid DNA in nuclear and/or mitochondrial genomes that generally contaminate even gradient-purified plastid fractions reduces the applicability of the highly sensitive PCR approach to monitor the absence of residual wild-type plastid chromosomes in transformed lines. It is therefore difficult, or even impossible, to assess reliably the hetero- or homoplastomic state of plastid transformants in this manner. By analysing wild-type and transplastomic mutants of tobacco, we demonstrate that separation of plastid chromosomes isolated from gradient-purified plastid fractions by pulsed-field gel electrophoresis can overcome the problem of (co)amplification of interfering promiscuous plastid DNA. PCR analyses with primers specific for plastid, mitochondrial and nuclear genes reveal an impressive purity of such plastid DNA fractions at a detection limit of less than one wild-type plastid chromosome copy per ten transplastomic cells.     

Increased in vivo frequency of IA-2 peptide-reactive IFNgamma+/IL-4- T cells in type 1 diabetic subjects

Active T cell recognition of islet antigens has been postulated as the pathogenic mechanism in human type 1 diabetes, but evidence is scarce. If T cells are engaged, they are expected to display increased clonal size and exhibit a T helper (Th)1/Th2 differentiation state. We used a peptide library that covers tyrosine phosphatase IA-2, a target antigen expressed in pancreatic beta cells, to probe 8 diabetic patients and 5 HLA-matched controls. When tested in a high resolution IFNgamma/IL-4 double color ELISPOT assay directly ex vivo, the number of IA-2-reactive IFNgamma producing cells was 17-fold higher in patients than in controls and IL-4 producing cells were not present. An average of 9 peptides was recognized in the patients vs. one in the controls. Determinant recognition primarily involved CD4+ cells and showed high variability among the patients. Furthermore, anti-CD28 antibody signal enhances quantitative assessment of effector T cells in T1D patients. In vitro expansion with peptides and IL-2 results in detection of responding cells in the controls and loss of disease specificity of the T cell response. Together these data provide strong evidence for the active targeting of IA-2 by Th1 memory effector cells in human type 1 diabetes.     

Effects of leptin and leptin fragments on steroid secretion and proliferative activity of regenerating rat adrenal cortex

Leptin, an adipose tissue-secreted hormone, acts via several isoforms of specific receptors (Ob-Rs), which may variously interact with the native leptin molecule and its fragments. Evidence has been provided that leptin affects rat adrenal functions, but the results were rather conflicting depending on the experimental condition examined (e.g. regenerating vs. mature or immature adrenal gland). Hence, we investigated the effects of three subcutaneous injections of murine leptin(1-147) and several leptin fragments (3 nmol/100 g body weight; 28, 16 and 4 h before the sacrifice) on the secretory activity and growth of regenerating rat adrenal cortex. The following leptin fragments were tested: murine leptin(116-130), and human leptin fragments 150-167, 138-167, 93-105, 22-56 and [Tyr]26-39. Leptin(1-147) enhanced plasma concentration of both aldosterone and corticosterone. The blood level of aldosterone was raised by leptin(116-130), leptin(138-167) and leptin(93-105), and that of corticosterone by leptin(93-105) and Tyr-leptin(26-39). Metaphase index (stachmokinetic method with vincristine) was unaffected by leptin(1-147), and lowered by leptin(116-130), leptin(150-167) and leptin(138-167). Collectively, our findings allow us to conclude that leptin and leptin fragments enhance the secretory activity and inhibit the growth of regenerating rat adrenal cortex, the biological activity of leptin being located in the C-terminal segment of its molecule.     

Reproduction of auditory and visual standards in monochannel cochlear implant users

The temporal reproduction of standard durations ranging from 1 to 9 seconds was investigated in monochannel cochlear implant (CI) users and in normally hearing subjects for the auditory and visual modality. The results showed that the pattern of performance in patients depended on their level of auditory comprehension. Results for CI users, who displayed relatively good auditory comprehension, did not differ from that of normally hearing subjects for both modalities. Patients with poor auditory comprehension significantly overestimated shorter auditory standards (1, 1.5 and 2.5 s), compared to both patients with good comprehension and controls. For the visual modality the between-group comparisons were not significant. These deficits in the reproduction of auditory standards were explained in accordance with both the attentional-gate model and the role of working memory in prospective time judgment. The impairments described above can influence the functioning of the temporal integration mechanism that is crucial for auditory speech comprehension on the level of words and phrases. We postulate that the deficits in time reproduction of short standards may be one of the possible reasons for poor speech understanding in monochannel CI users.     

Disturbance of motor imagery after cerebellar stroke

The authors studied the possible involvement of the cerebellum in nonexecutive motor functions needed for a normal performance of complex motor patterns by analyzing (using chronometric evaluation) finger movement sequences and their respective motor imagery (a mental simulation of motor patterns). Patients suffering from a cerebellar stroke (n=11) were compared with aged-matched control volunteers (n=11). Patients that had apparently recovered from a unilateral cerebellar stroke showed a marked slowing of motor performance in both hands (ipsi- and contralateral to lesion). This effect was accompanied by a similar slowing of motor imagery, suggesting that the cerebellum, traditionally implicated in the control of motor execution, is also involved in nonexecutive motor functions such as the planning and internal simulation of movements.     

Distribution of ganglionic sympathetic neurons supplying the subcutaneous,perirenal and mesentery fat tissue depots in the pig

Previous morphological studies revealed that the adipose tissue is innervated by adrenergic nerve fibers. Furthermore, physiological studies showed that the metabolism of adipose tissue is controlled by the adrenergic component of the nervous system. However, nothing is known on the sources of innervation of different fat tissue depots. Therefore, we decided to study the distribution of ganglionic sympathetic neurons innervating adipose tissue in the pig by means of a retrograde tracing method. We used 9 male and 9 female pigs of approximately 50 kg body weight. The retrograde tracer, Fast Blue (FB), was injected into the subcutaneous, perirenal and mesentery fat tissue depots. Results of the present study showed that numerous centers of the sympathetic nervous system innervate adipose tissue in the pig. FB+ neurons projecting to the subcutaneous fat tissue were placed in the thoraco-lumbar region of the sympathetic chain ganglia (SChG). However, neurons supplying perirenal and mesentery fat tissue depots were found in both the SChG and prevertebral ganglia (PVG). We conclude that different adipose tissue depots (subcutaneous, perirenal and mesentery) have different sources of innervation and that there is no significant difference in the distribution of neurons innervating adipose tissue in male and female pigs.