Summary
Mast cells have been implicated in the first line of defence against parasites and bacteria, but less is known about their role in anti‐viral responses. Allergic diseases often exacerbate ...during viral infection, suggesting an increased activation of mast cells in the process. In this study we investigated human mast cell response to double‐stranded RNA and viral infection. Cultured human mast cells were incubated with poly(I:C), a synthetic RNA analogue and live Sendai virus as a model of RNA parainfluenza virus infection, and analysed for their anti‐viral response. Mast cells responded to intracellular poly(I:C) by inducing type 1 and type 3 interferons and TNF‐α. In contrast, extracellular Toll‐like receptor 3 (TLR)‐3‐activating poly(I:C) failed to induce such response. Infection of mast cells with live Sendai virus induced an anti‐viral response similar to that of intracellular poly(I:C). Type 1, but not type 3 interferons, up‐regulated the expression of melanoma differentiation–associated gene 5 (MDA‐5) and retinoic acid‐inducible gene‐1 (RIG‐1), and TLR‐3, demonstrating that human mast cells do not express functional receptors for type 3 interferons. Furthermore, virus infection induced the anti‐viral proteins MxA and IFIT3 in human mast cells. In conclusion, our results support the notion that mast cells can recognize an invading virus through intracellular virus sensors and produce high amounts of type 1 and type 3 interferons and the anti‐viral proteins human myxovirus resistance gene A (MxA) and interferon‐induced protein with tetratricopeptide repeats 3 (IFIT3) in response to the virus infection.
Purpose: Increased risk of death has been reported in patients with intractable epilepsy (IE) taking nitrazepam (NZP).
Methods: Between January 1983 and March 1994, 302 patients with IE were entered ...into a NZP compassionate‐plea protocol. NZP was discontinued if there was <50% seizure reduction or significant side effects. In some patients with >50% reduction, it also was discontinued for lack of sufficient effect. At the end of follow‐up for this study, 62 patients remained taking NZP. Patients took NZP from 3 days to 10 years.
Results: Twenty‐one of 302 patients died after institution of NZP. Fourteen of 21 of these were taking NZP at death, and in five of 21, the NZP had been discontinued. Two patients were excluded from analysis, because it is unclear whether NZP had been discontinued before death. Six other patients were lost from follow‐up. Of the 14 deaths with NZP, seven were sudden, six were of pneumonia, and one was of cystinosis. Nine had at least one contributing factor, such as dysphagia, gastro‐esophageal reflux, or recurrent aspirations. The 294 patients took NZP for a total of 704 patient years (ptyrs), and were discontinued for a total of 856 ptyrs. There were 1.98 deaths/100 ptyrs on NZP compared with 0.58 deaths/100 ptyrs without NZP, most of the former being associated with side effects of NZP. Mortality in patients younger than 3.4 years was 3.98 with NZP compared with 0.26 deaths/100 ptyrs without NZP (p = 0.0002). Corresponding figures in patients 3.4 years or older were 0.50 and 0.86 deaths/100 ptyrs, respectively.
Conclusions: NZP therapy for epilepsy apparently increases the risk of death, especially in young patients with IE. This should be considered in antiepileptic drug (AED) management decisions.
To determine seizure propagation patterns, we analyzed ictal positron emission tomography (PET) studies of regional cerebral glucose utilization in 18 children (11 male and 7 female aged 2 weeks to ...16 years) with epilepsy (excluding infantile spasms IS). Three major metabolic patterns were determined based on degree and type of subcortical involvement: Nine children had type I; asymmetric glucose metabolism of striatum and thalamus. Of these, the 7 oldest children showed unilateral cortical hypermetabolism (always including frontal cortex) and crossed cerebellar hypermetabolism. Two infants (aged < 1 year) had a similar ictal PET pattern but no cerebellar asymmetry, presumably owing to immaturity of corticopontocerebellar projections. Five children had type II, symmetric metabolic abnormalities of striatum and thalamus; this pattern was accompanied by hippocampal or insular cortex hypermetabolism, diffuse neocortical hypometabolism, and absence of any cerebellar abnormality. Four children had type III, hypermetabolism restricted to cerebral cortex. This classification can accommodate ictal PET and single photon emission computed tomography (SPECT) patterns described by other investigators. Future studies should be directed at the clinical relevance of this classification, particularly with regard to epilepsy surgery.
We evaluated the clinical role of positron emission tomography (PET) in 23 children with tuberous sclerosis complex. Mean age of the children when first scanned was 3.3 years. Mean age when seizures ...began was 8.7 months. All, except three, were at least mildly developmentally delayed. PET images were visually analyzed and compared to computed tomography (CT), magnetic resonance imaging (MRI), and the electroencephalogram (EEG). In two infants, interictal PET study was normal. One of the studies was performed with a low resolution early generation scanner at age 7 months; the other infant was 2 days old. Twenty-one of the 23 children had focal or multifocal cortical hypometabolism. Some hypometabolic cortical regions on PET did not show corresponding abnormalities on CT and MRI, and may be due to epileptogenic mechanisms or small tubers. PET provides additional localizing information to CT and MRI in patients with tuberous sclerosis complex. However, because of the normally low cerebral glucose metabolism in infancy, PET may give false negative findings if performed prior to about 1 year of age. The usefulness of glucose metabolism PET in most patients with tuberous sclerosis complex is limited. However, if the EEG, CT, and MRI abnormalities are unifocal or unilateral, and surgery is being contemplated, more detailed evaluation with PET may help to determine if contralateral tubers are present and evaluate the functional integrity of the brain as a whole.
Multifaceted and idiosyncratic aberrancies in social cognition characterize autism spectrum disorders (ASDs). To advance understanding of underlying neural mechanisms, we measured brain hemodynamic ...activity with functional magnetic resonance imaging (fMRI) in individuals with ASD and matched-pair neurotypical (NT) controls while they were viewing a feature film portraying social interactions. Pearson's correlation coefficient was used as a measure of voxelwise similarity of brain activity (InterSubject Correlations-ISCs). Individuals with ASD showed lower ISC than NT controls in brain regions implicated in processing social information including the insula, posterior and anterior cingulate cortex, caudate nucleus, precuneus, lateral occipital cortex, and supramarginal gyrus. Curiously, also within NT group, autism-quotient scores predicted ISC in overlapping areas, including, e.g., supramarginal gyrus and precuneus. In ASD participants, functional connectivity was decreased between the frontal pole and the superior frontal gyrus, angular gyrus, superior parietal lobule, precentral gyrus, precuneus, and anterior/posterior cingulate gyrus. Taken together these results suggest that ISC and functional connectivity measure distinct features of atypical brain function in high-functioning autistic individuals during free viewing of acted social interactions. Our ISC results suggest that the minds of ASD individuals do not 'tick together' with others while perceiving identical dynamic social interactions.
To determine whether microscopic cortical lamination defects in patients with infantile spasms, not initially identifiable on MR, may be inferred from evolving changes in the adjacent white matter.
...Three infants between 3 and 6 months of age presented with infantile spasms. Based on negative metabolic assessment and normal MR findings, they were classified as cryptogenic. Despite therapy the children deteriorated with seizure recurrence and the advent of lateralizing clinical and neurophysiologic findings. MR studies were repeated and positron emission tomography was done.
The second MR studies demonstrated abnormalities of myelination, corresponding to localized clinical and neurophysiologic findings. Positron emission tomography findings did not show a strong correlation; one was normal, one showed no abnormality in the major area of MR abnormality, and one showed significantly less abnormality than on MR. Two patients have undergone surgery, both with good response.
Subtle lamination defects may be identifiable on positron emission tomography but are usually not detectable on MR. White matter abnormality on MR images is usually attributable to primary disease. We suggest that in certain cases progressive white matter changes may be induced as a secondary phenomenon by overlying microscopic cortical lamination defects. Serial MR imaging may be beneficial in children with infantile spasms in whom signs of laterality evolve.
We performed positron emission tomographic (PET) studies with 2-deoxy-218Ffluoro-D-glucose in 8 children with hemimegalencephaly (HME). HME is a developmental brain malformation associated with ...epilepsy, hemianopsia, and varying degrees of developmental delay. We hypothesized that the relatively poor overall developmental outcome of surgically hemispherectomized HME patients as a group, compared to children undergoing hemispherectomy for Sturge-Weber syndrome or chronic focal encephalitis, is related to dysfunction of the structurally "normal" non-HME side and that PET would be helpful in the pre-surgical evaluation of HME patients with intractable epilepsy. Visual analysis of the non-HME side on PET clearly revealed evidence of cortical hypometabolism in 4 patients compared to controls. Seven children underwent epilepsy surgery. One child had a glucose metabolic pattern suggesting a cortical lamination defect in the non-HME hemisphere, bilateral independent seizure onset, and was not considered to be a surgical candidate. We found a general correlation between the pattern of glucose utilization in the less affected hemisphere and prognosis. Although the follow-up periods are short, it is recommended that HME children with intractable epilepsy undergo hemispherectomy in the first year of life in order to allow maximal brain plasticity to occur; however, preoperative evaluation should also include an assessment of the integrity of the non-HME hemisphere.
Cyclooxygenase-2 and gastric carcinogenesis SAUKKONEN, KIRSI; RINTAHAKA, JOHANNA; SIVULA, ANNA ...
APMIS : acta pathologica, microbiologica et immunologica Scandinavica,
October 2003, Letnik:
111, Številka:
10
Journal Article
Recenzirano
Epidemiological studies have shown that the use of nonsteroid anti‐inflammatory drugs (NSAIDs) is associated with reduced risk of gastric cancer. The best‐known target of NSAIDs is the cyclooxygenase ...(Cox) enzyme. Two Cox genes have been cloned, of which Cox‐2 has been connected with gastric carcinogenesis. Expression of Cox‐2 is elevated in gastric adenocarcinomas, which correlates with several clinicopathological parameters, including depth of invasion and lymph node metastasis. This suggests that Cox‐2–derived prostanoids promote aggressive behavior of adenocarcinomas of the stomach. Cox‐2 expression is especially prominent in intestinal‐type gastric carcinoma and it is already present in dysplastic precursor lesions of this disease, which suggests that Cox‐2 contributes to gastric carcinogenesis already at the preinvasive stage. Our most recent data show that Cox‐2 is expressed in gastric adenomas of trefoil factor 1 deficient mice. Treatment of these mice with a Cox‐2 selective inhibitor, celecoxib, reduced the size of the adenomas. Taken together these data support efforts to initiate clinical studies to investigate the effect of Cox‐2 inhibitors as chemotherapeutic agents and as adjuvant treatment modalities against gastric neoplasias.
The Landau-Kleffner syndrome is sometimes associated with continuous spike-waves during slow-wave sleep. The clinical significance of this association is unclear. In order to investigate differences ...in glucose metabolic patterns between awake and sleep states in two children with Landau-Kleffner syndrome and continuous spike-waves during slow-wave sleep, fluorodeoxyglucose positron-emission tomographic (PET) studies were performed in each state. In the first patient, the awake interictal PET study revealed moderate hypometabolism in the thalamus and frontal and temporal cortex and mild hypometabolism in the parietal and anterior cingulate cortex bilaterally. Occipital cortex was severely hypometabolic bilaterally. In a repeat PET study performed during sleep in which continuous spike-waves during slow-wave sleep were present, the only difference noted compared to the awake study was a marked bilateral increase in temporal cortex metabolism. The awake interictal PET in the second child was normal, except for mildly increased relative glucose metabolism in the left inferior temporal cortex. The sleep PET study with continuous spike-waves during slow-wave sleep in this child showed hypermetabolism in both temporal lobes; however, this was more pronounced, with a wider distribution in the left temporal cortex. In normal subjects, PET studies performed during awake and sleep states have not revealed such differences. Whether the temporal lobes are involved in the generation of continuous spike-waves during slow-wave sleep remains to be confirmed in a larger group of patients. The first child was treated surgically with multiple subpial transection, following which continuous spike-waves during slow-wave sleep disappeared and language function improved.
Sleep habits and disorders in Finnish schoolchildren SAARENPÄÄ‐HEIKKILÄ, OUTI A.; RINTAHAKA, PERTTI J.; LAIPPALA, PEKKA J. ...
Journal of sleep research,
September 1995, Letnik:
4, Številka:
3
Journal Article
Recenzirano
Odprti dostop
SUMMARY A variety of epidemiological sleep parameters was evaluated in 574 Finnish schoolchildren (age 7 to 17 years) and in their parents (454 mothers and 390 fathers). Three questionnaire forms ...were set, one for the pupil and two for his/her parents including information of sleep habits, disorders, and social background of the pupil and his/her family. The pupils were grouped by age (two preadolescent groups: 7.1–9.3 y and 9.4–13 y, adolescents 13.1–17.1 y) and sex. It was found that bedtime was more often after 22.00 hours among adolescents than preadolescents both at weekends and on weekdays. At weekends the wake‐up time was later in adolescents than preadolescents but on weekdays it was opposite in boys. On weekdays girls went earlier to bed than boys and woke up earlier than boys. Total sleep durations both on weekdays and at weekends were longer in preadolescent than in adolescent groups, and longer during weekend nights than on weekday nights in all groups. Girls experienced more dreaming and night waking, but boys snored more. Daytime sleepiness patterns were more common in adolescents than in preadolescents. Children who experienced daytime sleepiness more often had fathers with daily sleep urges.
An association was found between age and sleep habits and some daytime sleepiness patterns; adolescents went to bed later and slept less, and had more problems with alertness during daytime than preadolescents. Some differences were also found between boys and girls. The daytime sleepiness of pupils correlated with the same symptom in fathers.
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