Autoreactive T cells target peripheral nerves in Guillain-Barré syndrome.

Guillain-Barré syndrome (GBS) is a rare heterogenous disorder of the peripheral nervous system, which is usually triggered by a preceding infection, and causes a potentially life-threatening progressive muscle weakness1. Although GBS is considered an autoimmune disease, the mechanisms that underlie its distinct clinical subtypes remain largely unknown. Here, by combining in vitro T cell screening, single-cell RNA sequencing and T cell receptor (TCR) sequencing, we identify autoreactive memory CD4+ cells, that show a cytotoxic T helper 1 (TH1)-like phenotype, and rare CD8+ T cells that target myelin antigens of the peripheral nerves in patients with the demyelinating disease variant. We characterized more than 1,000 autoreactive single T cell clones, which revealed a polyclonal TCR repertoire, short CDR3ß lengths, preferential HLA-DR restrictions and recognition of immunodominant epitopes. We found that autoreactive TCRß clonotypes were expanded in the blood of the same patient at distinct disease stages and, notably, that they were shared in the blood and the cerebrospinal fluid across different patients with GBS, but not in control individuals. Finally, we identified myelin-reactive T cells in the nerve biopsy from one patient, which indicates that these cells contribute directly to disease pathophysiology. Collectively, our data provide clear evidence of autoreactive T cell immunity in a subset of patients with GBS, and open new perspectives in the field of inflammatory peripheral neuropathies, with potential impact for biomedical applications.

[Births and children after assisted reproductive technologies. A retrospective analysis with special regard to multiple pregnancies at the Department of Obstetrics and Gynecology, Paracelsus Medical University Salzburg (2000-2009) with an extrapolation for Austria]. / Geburten und Kinder nach assistierter Fortpflanzungshilfe. Eine retrospektive Analyse unter besonderer Berücksichtigung von Mehrlingsschwangerschaften an der Universitätsklinik für Frauenheilkunde und Geburtshilfe Salzburg (2000-2009) mit einer Hochrechnung für Österreich.

BACKGROUND: Austria still lacks a baby-take-home rate after assisted reproductive technologies (ART) and therefore an adequate quality management of ART. PATIENTS AND METHODS: This paper extrapolates data about births/infants after ART at the University Clinic of Obstetrics and Gynaecology (PMU/SALK) in Salzburg for Austria, especially in regard to multiple births/infants collected between 2000 and 2009. RESULTS: On average 2 271 infants were born per year during the last 10 years. Among them, 76 infants (3.34% of all children) were born after ART. Of all children conceived by ART and born (759) at the University Clinic of Obstetrics and Gynaecology 368 are multiples. This is 48.5% of all children born after ART. 31.6% of all multiples born were conceived through ART. DISCUSSION: The extrapolation of data concerning multiples results in 1 255 multiples/year after ART for Austria. CONCLUSION: Without a baby-take-home rate, serious quality management of reproductive medicine is impossible. Online registration of deliveries and infants is the only adequate approach. The data of this statistical extrapolation from a single perinatal center not only provide a survey about the situation in Austria, but also support the claim of a quantitative (numbers) as well as qualitative (condition of infants) baby-take-home rate after ART.

Transient outward potassium current in rabbit atrium is depressed after short-time rapid atrial pacing but recovers after a longer pacing period.

In rabbit, after short-time rapid atrial pacing (RAP), atrial ion currents are reduced similarly as in human chronic atrial fibrillation (AF). Using the rabbit model, time-course of transient outward potassium current (I(to)) remodeling due to RAP was studied. RAP (600 bpm) was applied via an atrial lead for 0 (control), 24 and 120 h, n = 4 animals/group. Using patch clamp technique in whole-cell mode, current densities and biophysical properties were measured in isolated atrial myocytes. After 24 h of RAP, a reduction of peak I(to) (mean +/- SEM, test potential +50 mV, +37 degrees C) was observed (60.3 +/- 5.4 pA/pF (control, n = 20) vs. 28.0 +/- 2.5 pA/pF (24 h, n = 21)). Inactivation of I(to) was slower after 24 h, other biophysical properties were unaltered. However, I(to) recovered after 120 h: 51.7 +/- 4.5 pA/pF (n = 26, p = n.s. vs. control). Inactivation tended to also recover to initial values but was still different to control. Early I(to) remodeling due to RAP in rabbits seems to be more complex than previously thought: a time course of I(to) remodeling with swayings has to be considered when using the rabbit model of RAP in order to study early remodeling or rather its therapeutic manipulation.

[Blocking adhesion molecules with natalizumab in multiple sclerosis]. / Blockade von Adhäsionsmolekülen mit Natalizumab in der Therapie der Multiplen Sklerose. Aktueller Studienstand.

Natalizumab is a humanized, monoclonal antibody, that inhibits adhesion molecules (alpha(4)-integrins) on the surface of immune cells. These adhesion molecules are important for binding of lymphocytes to endothelial cells of blood vessels and infiltration of inflammatory cells into tissues. Natalizumab is currently being tested in large clinical trials for the treatment of multiple sclerosis (MS) and other autoimmune diseases (inflammatory bowel diseases, rheumatoid arthritis). After demonstrating the safety and potential effectiveness of natalizumab in MS therapy during shorter treatment periods (

The sex determination in Ellobius lutescens remains bizarre.

Mammalian sex determination and gonad differentiation are the result of a complex interaction of fine-tuned spatial and temporal gene expression with threshold levels of individual genes. The male pathway is initiated by SRY. Some exceptional mammals determine male sex without the SRY gene and even without a Y chromosome. Ellobius lutescens in this report is one example of this "weird" species. We provide key data on the genomic level that there are no coarse differences in the genomes of male and female animals by comparative genomic hybridization. On the gene level we studied the gene Nr5a1 for the orphan nuclear receptor, steroidogenic factor SF-1, a central constituent for gonad differentiation and adrenal gland development. The Ellobius lutescens Nr5a1 gene was mapped to the proximal short arm of chromosome 2 by fluorescence in situ hybridization. In addition, we provide evidence by linkage analysis in two E. lutescens pedigrees that Nr5a1 is not the key male sex-determining gene in Ellobius lutescens.

Mechanisms of Staphylococcus aureus induced apoptosis of human endothelial cells.

Staphylococcus aureus plays an important role in sepsis, pneumonia and wound infections. Here, we demonstrate that infection with several S. aureus strains results in apoptosis of human endothelial cells. S. aureus induced an activation of cellular caspases, the acid sphingomyelinase, a release of cytochrome c and a stimulation of Jun NH2-terminal kinase (JNK). The significance of these findings is indicated by a prevention of S. aureus triggered apoptosis of human cells deficient for ASM or upon genetic or pharmacological inhibition of JNK or caspases, respectively.

Type 2 diabetes in children and adolescents: an emerging disease.

The incidence of type 2 diabetes is increasing in the United States, and minority populations in particular seem to be affected. In the past, it was thought that type 2 diabetes occurred only in adults. However, an alarming epidemic has emerged, and children as young as 8 years of age are now being diagnosed with the disease. The purpose of this article is to present pediatric nurse practitioners with the most recent information about type 2 diabetes in children and adolescents, summarize current understanding about diagnosis, and outline treatment options.

Feminization as a critical component of the changing hydrosocial contract.

The Dublin Principles recognize the role that women play in water resources management. The South African Minister of Water Affairs, Prof. Kader Asmal, coined a new expression by referring to the "feminization of water". The article explores some of the ramifications of this and shows that the two aspects are not necessarily the same thing. Feminization does not necessarily mean bringing more women into management processes as it is often depicted. This is the quantitative aspect that is often referred to by male managers and it has been given a negative implication as a result. The more important issue is the qualitative aspect that involves processes such as stakeholder participation, viewing alternatives before a decision is made and accountability.

Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes.

OBJECTIVE: Children with type 1 diabetes are frequently difficult to manage during times of gastroenteritis or poor oral intake of carbohydrates because of mild or impending hypoglycemia. The present study describes the effective use of small doses of subcutaneous glucagon in these children. RESEARCH DESIGN AND METHODS: We analyzed 33 episodes of impending or mild hypoglycemia in 28 children (ages 6.6 +/- 0.7 years). All were healthy except for type 1 diabetes and an episode of gastroenteritis. Using a standard U-100 insulin syringe, children ages < or = 2 years received two "units" (20 microg) of glucagon subcutaneously and those ages >2 years received one unit/year of age up to 15 units (150 microg). If the blood glucose did not increase within 30 min, the initial dosage was doubled and given at that time. We used patients' self-glucose monitoring devices, aqueous glucagon, standard insulin syringes, and frequent phone contact with a physician and/or a diabetes nurse educator in this study. RESULTS: Blood glucose was 3.44 +/- 0.15 mmol/l before and 8.11 +/- 0.72 mmol/l 30 min after glucagon. In 14 children, relative hypoglycemia recurred, requiring retreatment (3.48 +/- 0.18 to 6.94 +/- 0.72 mmol/l). In four children, a third dose was required. The glucagon was well tolerated In 28 of the 33 episodes of impending hypoglycemia, the children remained at home and fully recovered. Five children were taken to their local hospital because of concerns of dehydration or fever, but none for hypoglycemia. CONCLUSIONS: Mini-dose glucagon rescue, using subcutaneous injections, is effective in managing children with type 1 diabetes during episodes of impending hypoglycemia due to gastroenteritis or poor oral intake of carbohydrate.

Spectral karyotyping of mouse cell line WMP2.

We have evaluated the mouse cell line WMP2 using both GTG-banding analysis and spectral karyotyping to verify the reliability of using this established cell line derived from WMP/WMP mice. The WMP cell lines contain easily identifiable metacentric fusion chromosomes and are used extensively for gene mapping. Because of karyotypical changes in the WMP1 cell line, WMP2 was examined. Our results demonstrate that WMP2 is stable during culture, and the karyotype is simple and easy to use. Based on the findings discussed in this paper, we recommend the use of the WMP2 cell line for future prospective gene mapping in the mouse.

Comparing outpatient and inpatient diabetes education for newly diagnosed pediatric patients.

PURPOSE: The purpose of this study was to compare the efficacy of outpatient vs inpatient programs on medical, cognitive, behavioral, and psychosocial outcomes. METHODS: Using three large, tertiary medical centers in the United States, the sample of 32 children newly diagnosed with diabetes and their parents were recruited. Children and parents who received outpatient education were compared with those who received inpatient education. The following outcome variables were compared: (1) rates of hospital readmissions and/or emergency room visits for either severe hypoglycemia or ketoacidosis, (2) knowledge, (3) sharing of responsibilities, (4) adherence, (5) family functioning, (6) coping, and (7) quality of life. RESULTS: In general, no statistically significant differences were found between the groups. A trend was noted in the outpatient group with regard to improved use of emergency precautions on the adherence measure, roles on the family functioning measure, maintaining family integration on the parental coping measure, and disposition on the children's coping instrument. CONCLUSIONS: Findings support the safety and efficacy of the outpatient program method.

Nutrition in pediatric primary care: assessment and common problems.

As health promotion and disease prevention gain prominence, nutritional assessment and intervention become important tools for the NP. The nutritional needs of the growing child and adolescent are explored, with a discussion about common nutritional deficits seen in the pediatric population.

Genotype-phenotype correlations in phenylketonuria.

Genotyping of the phenylalanine hydroxylating system offers a new way of characterizing patients with phenylalanine hydroxylase (PAH) deficiency. This paper investigates the power of genotyping as a parameter for differential diagnosis and as a measure of the risk factor of brain damage in well-treated patients with phenylketonuria (PKU). Thirty-three PKU patients were followed up over 9 years and the quality of dietary treatment, plasma phenylalanine (phe) in the newborn period before treatment and intellectual outcome at the age of 9 years were measured and correlated with the predicted residual activity (PRA) of the phe hydroxylase system as estimated from mutation analysis of the PAH gene. Patients were grouped in group Ia (PRA = 0%), group Ib (PRA = 5-15%) and group II (PRA > or = 25% of the normal activity). Mean plasma phe levels in the newborn in group Ia were 37.9 +/- 6.5 (2296 +/- 394), in group Ib 40.8 +/- 15.9 (2472 +/- 963) and in group II 16.2 +/- 4.2 (981 +/- 254) mg/dl (mumol/l). Difference in mean plasma values of groups Ia and Ib on the one hand and group II on the other were highly significant (P < 0.0001). No difference could be seen between groups Ia and Ib. There was a higher mean IQ at the age of 9 years in group II (97.4 +/- 5.4) in comparison with groups Ia (92.7 +/- 12.8) and Ib (85.0 +/- 14.4). The difference between group Ib and group II was significant (P < 0.040).(ABSTRACT TRUNCATED AT 250 WORDS)

Reliability and validity of the Diabetes Family Behavior Scale (DFBS).

The Diabetes Family Behavior Scale (DFBS) was designed to measure diabetes-specific family support. The purposes of this study were to refine the scale and to assess reliability and criterion validity in terms of relationship to metabolic control. The DFBS was administered to 321 children and adolescents with insulin-dependent diabetes mellitus (IDDM). Blood was drawn for determination of glycosylated hemoglobin (HbA1c). Based on an item-analysis procedure, the DFBS was revised to include 47 items with two subscales, one to reflect guidance-control and one to reflect warmth-caring. Acceptable internal consistency was found for the DFBS total score (.86), and for the guidance-control (.81) and warmth-caring (.79) subscales. There was a statistically significant relationship in the expected direction between DFBS total score and HbA1c (r = -.12, P < .03), and between the guidance-control subscale and HbA1c (r = -.17, P < .002).

Teaching assertive communication skills to adolescents with diabetes: evaluation of a camp curriculum.

Diabetes management requires consistently implementing adherence behaviors in a variety of settings. For some adolescents, consistency may be difficult due to problems in communication and assertiveness. The purpose of the present study was to evaluate the impact of a camp curriculum to teach assertive communication skills to adolescents with diabetes. The curriculum included didactic information, sharing of personal experiences, and role playing. Results showed a significant increase in adolescents' perceptions of their assertiveness from before to after the camp experience, an increase that was still apparent at a 3-month follow-up. No changes were reported in parental perceptions of their adolescents' degree of openness in communicating or in communication problems. In contrast, adolescents reported a significant decrease in their degree of openness in communicating with fathers, with a similar trend for mothers. These results suggest that the curriculum was successful in meeting the primary goal of enhancing the adolescents' assertive communication skills but had a questionable impact on their general communications with parents.

Identification of a new missense mutation in Japanese phenylketonuric patients.

A new missense mutation in the phenylalanine hydroxylase (PAH) gene was identified in 20/30 members of the families of 10 unrelated Japanese phenylketonuria (PKU) patients from Kyushu island. The point mutation was present in 20 of 40 mutant alleles. This was proved by DNA sequence analysis after polymerase chain reaction (PCR) amplification and allele-specific oligonucleotide (ASO) hybridization. This point mutation, an A to G transition at the first base of codon 276 in exon 7, resulted in an amino acid substitution. Methionine was replaced by valine and the mutation was found to be associated with restriction fragment length polymorphism (RFLP) haplotype 4 in the investigated patients. The mutation was not found in 24 unrelated Caucasian patients from different countries. These findings may indicate a founder effect in the transmission of the mutation.

Haplotype distribution and mutations at the PAH locus in Croatia.

Restriction fragment length polymorphism (RFLP) haplotypes and mutations at the phenylalanine hydroxylase (PAH) locus have been studied in 25 unrelated families from Croatia. The results of RFLP analysis demonstrated that 80% of the mutant alleles were associated with three haplotypes (1, 2 and 4). Eight mutations were detected on the background of six mutant haplotypes, comprising 68% of phenylketonuria (PKU) alleles in Croatia. The mutation in codon 408 was most frequent, as was the haplotype 2 allele with which it was associated. These data are in accordance with formerly published population genetic analyses at the PAH locus, and with studies revealing the molecular basis of the phenotypic heterogeneity of PKU. The codon 281 mutation was more frequent in Croatia than previously observed in other populations.

The status of nursing administrators in Hungary.

The College for Health Workers was established in 1973 in Hungary with the aim to educate and train highly qualified healthcare workers to meet all the demands of special health care. Although matrons (nursing administrators) who have graduated from the College are capable of performing special tasks to ensure quality care, they do not have the corresponding authority and recognition. Below, how nurse researchers in Hungary proved this hypothesis.