Developmental aspects of children's behavior and safety while cycling

OBJECTIVE: To examine children's competence while cycling, as demonstrated in mistakes in performance and failure to comply with safety rules. METHODS: Children in three age groups (8, 10, and 12 years) participated in a realistic yet simulated traffic environment. RESULTS: The boys' cycling speed increased steadily with age, while that of the girls increased from 8 to 10 but decreased at age 12. Most children had adequate motor control by age 10, and the youngest compensated for their less developed skills by cycling slowly and braking early at junctions. Serious mistakes, often related to the children's age and gender, consisted of the children failing to stop at signals or stopping too late, especially at short stopping range. CONCLUSIONS: There are considerable individual differences in children's cycling competence that are related to biological factors, such as age and gender, and psychological factors, such as rule compliance and choice of cycling speed.     

Chemoattractant-induced NADPH oxidase activity in human monocytes is terminated without any association of receptor-ligand complex to cytoskeleton

When the chemotactic peptide formylmethionyl-leucyl-phenylalanine binds to its cell surface receptor, a transmembrane signal is generated that activates the superoxide-producing NADPH oxidase of human phagocytes. Comparing monocytes and neutrophils with regard to the production of superoxide anion induced by the peptide, we found a similar time-course for both types of cells. In neutrophils, ligand binding induced a conversion of the receptor to a high-affinity form, a change suggested to be due to an association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton. This event has been hypothesized to terminate the signal that activates the NADPH oxidase and thereby results in cessation of the cellular production of superoxide anion. Neutrophils preincubated with the cytoskeleton-disrupting drug cytochalasin B showed an increased and prolonged superoxide anion production after activation with the peptide, thus indicating that the cytoskeleton is involved in terminating this response. Formylmethionyl-leucyl-phenylalanine was also found to induce polymerization of actin in monocytes; however, cytochalasin B had no effect on the peptide-induced generation of superoxide anion in these cells. Furthermore, also in monocytes, ligand binding induced a conversion of the receptor to a high-affinity form; however, the receptor-ligand complex did not coisolate with the Triton X-100-insoluble cytoskeleton. These results indicate that, in monocytes, the NADPH oxidase activating pathway is terminated without any association of the receptor-ligand complex to the Triton X-100-insoluble cytoskeleton.     

Thiols decrease cytokine levels and down-regulate the expression of CD30 on human allergen-specific T helper (Th) 0 and Th2 cells

The thiol antioxidant N-acetyl- L-cysteine (NAC), known as a precursor of glutathione (GSH), is used in AIDS treatment trials, as a chemoprotectant in cancer chemotherapy and in treatment of chronic bronchitis. In vitro, GSH and NAC are known to enhance T cell proliferation, production of IL-2 and up-regulation of the IL-2 receptor. The 120-kD CD30 surface antigen belongs to the tumour necrosis factor (TNF) receptor superfamily. It is expressed by activated T helper (Th) cells and its expression is sustained in Th2 cells. We have analysed the effect of GSH and NAC on the cytokine profile and CD30 expression on human allergen-specific T cell clones (TCC). TCC were stimulated with anti-CD3 antibodies in the presence of different concentrations of GSH and NAC. Both thiols caused a dose dependent down-regulation of IL-4, IL-5 and IFN-gamma levels in Th0 and Th2 clones, with the most pronounced decrease of IL-4. Furthermore, they down-regulated the surface expression of CD30, and the levels of soluble CD30 (sCD30) in the culture supernatants were decreased. In contrast, the surface expression of CD28 or CD40 ligand (CD40L) was not significantly changed after treatment with 20 m M NAC. These results indicate that GSH and NAC favour a Th1 response by a preferential down-regulation of IL-4. In addition, the expression of CD30 was down regulated by GSH and NAC, suggesting that CD30 expression is dependent on IL-4, or modified by NAC. In the likely event that CD30 and its soluble counterpart prove to contribute to the pathogenesis in Th2 related diseases such as allergy, NAC may be considered as a future therapeutic agent in the treatment of these diseases.     

Estrogen and the relaxant effect of intramural noradrenaline on calcium induced contractures in depolarized rat uterus

The influence of intramural noradrenaline on calcium induced contractures was studied in isolated preparations of rat uterus. The depolarized (127 mM KCl) myometrium of oophorectomized rats responded with contraction followed by a transient relaxation when exposed to 3 mM calcium. The threshold concentration of calcium, where the transient relaxation began to appear, was between 0.25 and 0.5 mM. Blockade of the beta-adrenoceptors with propranolol or noradrenaline depletion with reserpine completely removed the transient relaxation, indicating that the latter was due to release of intramural noradrenaline. Estrogen treatment abolished the relaxant effect of intramural noradrenaline, whereas progesterone was ineffective in this respect. Preparations from rats in natural estrus responded like estrogenized tissues, and diestrus preparations behaved as uteri of oophorectomized rats without estrogen treatment.     

Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific,unrestricted cytotoxic T cells

Cytotoxic T cells (CTL) recognize target proteins as short peptides presented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T cell receptor (TCR) recognition of target proteins and non-protein structures. How such T cell responses are generated is presently unclear. We generated carbohydrate (CHO)-specific, MHC-unrestricted CTL responses by coupling di- and trisaccharides to K^b- or D^b-binding peptides for direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central positions on the carrier peptide. With two of these glycopeptides, with galabiose (Galα1-4Gal; Gal₂) bound to a homocysteine (via an ethylene spacer arm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-derived peptide (RGYVYQGL binding to K^b), CTL were generated which preferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal₂ epitope in a glycolipid. By fractionation of CTL, preliminary data indicate that glycopeptide-specific K^b-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The results demonstrate that hapten-specific unrestricted CTL responses can be generated with MHC class I-binding carrier peptides. Different models that might explain the generation of such responses are discussed.     

How well do nurse-run telephone consultations and consultations in the surgery agree? Experience in Swedish primary health care.

The telephone consultation service is an important part of Swedish primary health care. However, few studies have compared telephone consultations managed by nurses with surgery consultations managed by both doctors and nurses in terms of information obtained from the patient regarding his or her symptoms, and the management decisions made. In this study, the information obtained from a patient during a telephone consultation with a health centre nurse and the management decisions made, were compared with those obtained at a subsequent surgery consultation with the same nurse, and then with a doctor. Of 200 telephone consultations at a health centre (50 in each of the following four categories as defined by the management decision of the nurse: acute case, semi-acute case, referral case and self-care case), 193 patients were included in the study. The information given to the nurse during the telephone consultation was recorded. The patient was then asked to come for a surgery consultation on the same day, first with the same nurse and then with a general practitioner. A comparison was made between the information obtained and the decisions taken in these three situations. In 185 of the 193 cases (96%) the information led to the same management decision by the nurse, in both the telephone consultation and later in the surgery consultation. In all cases the same history was recorded by the nurse during the telephone and surgery consultations as by the general practitioner. This indicates that in most cases little or no information is missed in a telephone consultation with a nurse as compared with a surgery consultation with a nurse or doctor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term corticosteroid treatment in giant cell arteritis

Ninety patients with giant cell arteritis were followed up 9-16 years (median 11.3 years) after diagnosis. The mean duration of corticosteroid therapy was 5.8 years (range 0-12.8 years). Together, the patients had received corticosteroids for 492 patient-years. Five years after diagnosis, 43% of the patients were on corticosteroid therapy. After 9 years, 15 of 60 surviving patients (25%) were still being treated with 1.25-10 mg of prednisolone daily (median dose 5 mg). The relapse rate was about 50%, regardless of the time after diagnosis, when an attempt to withdraw the treatment was made. Forty-six per cent of the relapses occurred within one month and 96% within one year of the end of treatment. Most of the flare-ups occurred during the first year of therapy and in 55% of the patients on a prednisolone dosage of 5 mg or less. We did not find any increase in morbidity in our patients compared to the general population. Nor did we see any significant complications which we could attribute to the steroid treatment.     

P2 receptor mRNA expression profiles in human lymphocytes,monocytes and CD34+ stem and progenitor cells

Background  

Extracellular nucleotides (ATP, ADP, UTP and UDP) exert a wide range of biological effects in blood cells mediated by multiple ionotropic P2X receptors and G protein-coupled P2Y receptors. Although pharmacological experiments have suggested the presence of several P2 receptor subtypes on monocytes and lymphocytes, some results are contradictory. Few physiological functions have been firmly established to a specific receptor subtype, partly because of a lack of truly selective agonists and antagonists. This stimulated us to investigate the expression of P2X and P2Y receptors in human lymphocytes and monocytes with a newly established quantitative mRNA assay for P2 receptors. In addition, we describe for the first time the expression of P2 receptors in CD34⁺ stem and progenitor cells implicating a potential role of P2 receptors in hematopoietic lineage and progenitor/stem cell function.     

Nicotinamide does not influence cytokines or exhaled NO in human experimental endotoxaemia

This study examined the hypothesis that nicotinamide could attenuate endotoxin-induced inflammatory responses in humans as indicated by levels of cytokines and nitric oxide. Ten healthy male volunteers participated in a randomised, double-blind, cross-over design with regard to the effects of nicotinamide. The volunteers received orally 4 g nicotinamide or placebo at 14 h and at 2 h preceding the experiment (total dose of 8 g). Endotoxin (E. coli, 2 ng/kg), was administered intravenously. Blood samples and haemodynamic data were collected prior to and up to 6 h after the endotoxin infusion. Orally exhaled NO was measured hourly. Following endotoxin, body temperature increased from baseline 36.3 +/- 0.09 degrees C to a maximum of 38.0 +/- 0.1 degrees C for all (mean +/- SEM, P < 0.001) and heart rate increased from 59 +/- 1.9 to 87.0 +/- 2.6 beats/min after 3 h (mean +/- SEM, P < 0.001). Endotoxin challenge also markedly elevated the TNF-alpha, IL-6, IL-8 and IL-10 concentrations (P < 0.001 versus baseline for all) during the study period. Orally exhaled NO also increased (P < 0.01) compared to baseline. Nicotinamide treatment did not influence the patterns of cytokine and NO response to endotoxin. In conclusion, there was no effect on the inflammatory parameters by oral nicotinamide at a dose of 8 g, limiting the potential use of this agent for anti-inflammatory purpose in man.     

Determination of gene organization in the human IGHV region on single chromosomes

Organization of the IGHV genes (n=108) on single human chromosomes has been determined by detecting these sequences in single sperm using multiplex PCR amplification followed by microarray detection. A total of 374 single sperm samples from five Caucasian males were studied. Three deletion/insertion polymorphisms (Del I-Del III) with deletion allele frequencies ranging from 0.1 to 0.3 were identified. Del I is a previously reported polymorphism affecting three IGHV genes (IGHV1-8, IGHV3-9, and IGHV2-10). Del II affects a region 2-18 kb containing two pseudogenes IGHV(II)-28.1 and IGHV3-29, and Del III spans approximately 21-53 kb involving genes IGHV4-39, IGHV7-40, IGHV(II)-40-1, and IGHV3-41. Deletion alleles of both Dels II and III were found in a heterozygous state, and therefore, could not be easily detected if haploid samples were not used in the study. Results of the present study indicate that deletions/insertions together with other possible chromosomal rearrangements may play an important role in forming the genetic structure of the IGHV region, and may significantly contribute to antibody diversity. Since these three polymorphisms are located within or next to the 3' half of the IGHV region, they may have an important role in the expressed IGHV gene repertoire during immune response.