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Pathway Dysfunction (pathway + dysfunction)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Triple negative tumours: a critical review

HISTOPATHOLOGY, Issue 1 2008
J S Reis-Filho
Breast cancer is a heterogeneous disease that encompasses several distinct entities with remarkably different biological characteristics and clinical behaviour. Currently, breast cancer patients are managed according to algorithms based on a constellation of clinical and histopathological parameters in conjunction with assessment of hormone receptor (oestrogen and progesterone receptor) status and HER2 overexpression/gene amplification. Although effective tailored therapies have been developed for patients with hormone receptor-positive or HER2+ disease, chemotherapy is the only modality of systemic therapy for patients with breast cancers lacking the expression of these markers (triple-negative cancers). Recent microarray expression profiling analyses have demonstrated that breast cancers can be systematically characterized into biologically and clinically meaningful groups. These studies have led to the re-discovery of basal-like breast cancers, which preferentially show a triple-negative phenotype. Both triple-negative and basal-like cancers preferentially affect young and African-American women, are of high histological grade and have more aggressive clinical behaviour. Furthermore, a significant overlap between the biological and clinical characteristics of sporadic triple-negative and basal-like cancers and breast carcinomas arising in BRCA1 mutation carriers has been repeatedly demonstrated. In this review, we critically address the characteristics of basal-like and triple-negative cancers, their similarities and differences, their response to chemotherapy as well as strategies for the development of novel therapeutic targets for these aggressive types of breast cancer. In addition, the possible mechanisms are discussed leading to BRCA1 pathway dysfunction in sporadic triple-negative and basal-like cancers and animal models for these tumour types. [source]

Afferent pathway dysfunction in children with primary nocturnal enuresis

INTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2010
Linya Lv
Objectives: To investigate afferent pathway dysfunction in children with primary nocturnal enuresis by measuring pudendal somatosensory evoked potential and tibial somatosensory evoked potential. Methods: Subjects with primary nocturnal enuresis, 36 boys and 18 girls, aged from 5 to 16 years, were enrolled in this study: 24 subjects had complicated primary enuresis (CPE) and 30 subjects had monosymptomatic primary enuresis (MPE). There were no differences in bodyweight or gender between the MPE and CPE groups (P > 0.05). All of the children underwent physical examination, urine analysis, urinary ultrasound and spinal magnetic resonance imaging. Only subjects without urological and neurological abnormalities (with the exception of spina bifida occulta, which was found in some of the patients) were included in this neurophysiological study. Results: There were 20 children who were positively recorded with pudendal somatosensory evoked potential in the CPE group, and all of the children in the MPE group were positively recorded (P < 0.05). Positive records of tibial somatosensory evoked potential were successfully achieved in both groups. Furthermore, the pudendal and tibial conductive velocity were slower as compared to the normal range, especially in children in the CPE group (P < 0.001). Conclusions: Afferent pathway function may be impaired by some factors, which should be considered by both clinicians and parents. [source]

Isoprenoid pathway dysfunction in chronic fatigue syndrome

ACTA NEUROPSYCHIATRICA, Issue 5 2003
Ravi Kumar Kurup
Background and aims:, The isoprenoid pathway was assessed in 15 patients with chronic fatigue syndrome (CFS). The pathway was also assessed in individuals with differing hemispheric dominance to assess whether hemispheric dominance has any correlation with these disease states. Methods:, The isoprenoid metabolites , digoxin, dolichol and ubiquinone , RBC membrane Na+ -K+ ATPase activity, serum magnesium and tyrosine/tryptophan catabolic patterns were assessed. The free radical metabolism, glycoconjugate metabolism and RBC membrane composition were also assessed. Results:, Membrane Na+ -K+ ATPase activity and serum magnesium levels were decreased while HMG-CoA reductase activity and serum digoxin levels were increased in CFS. There were increased levels of tryptophan catabolites , nicotine, strychnine, quinolinic acid and serotonin , and decreased levels of tyrosine catabolites ,dopamine, norepinephrine and morphine , in CFS. There was an increase in dolichol levels, carbohydrate residues of glycoproteins, glycolipids, total/individual glycosaminoglycans (GAG) fractions and lysosomal enzymes in CFS. Reduced levels of ubiquinone, reduced glutathione and free radical scavenging enzymes as well as increased lipid peroxidation products and nitric oxide were noticed in CFS. The biochemical patterns in CFS correlated with those obtained in right hemispheric dominance. Conclusions:, The role of hypothalamic digoxin and neurotransmitter-induced immune activation, altered glycoconjugate metabolism and resultant defective viral antigen presentation, NMDA excitotoxicity and cognitive and mitochondrial dysfunction in the pathogenesis of CFS is stressed. CFS occurs in individuals with right hemispheric dominance. [source]

Studying electrophysiological characteristics in children with congenital sensory nystagmus- case presentations

ACTA OPHTHALMOLOGICA, Issue 2009
J BRECELJ
Purpose In classification of sensory congenital nystagmus (CN) is important to recognize the underlying retinal or visual pathway dysfunction. The aim was to distinguish ERGs and VEPs charcteristics which may identify among variety of disorders associated with sensory CN. Methods In infants and small children that were ophthalmologically classified as sensory CN were ERGs and VEPs recorded simultaneously in the same session. ERGs were detected without dilated pupils and with skin electrodes. Under darkened laboratory conditions were ERGs recorded to white (cone/rod mediated response) and dim blue (rod mediated response) flash and under lighten room were ERGs recorded to white, red and 30 Hz flicker flash (cone mediated responses). VEPs were recorded from three occipital electrodes to flash and onset stimulation. Results Cases with abnormal ERGs showed: in Leber's congenital amaurosis were undetectable both rod and cone mediated responses from early infancy; in cone-rod retinal dystrophy abnormal cone and rod mediated responses progressed in time; in achromatopsia abnormal cone mediated responses did not progress in time; in congenital stationary night blindness a negative ERG did not progress in time. Cases with abnormal VEPs showed: in ocular albinism VEP contralateral asymmetry; in achiasmia VEP ipsilateral asymmetry; in severe optic nerve hypoplasia flash VEP was non-recordable, while in moderate optic nerve hypoplasia flash and pattern onset VEP findings might not correlate with clinic findings. Conclusion Sensory CN is associated with a variety of disorders affecting the retina, optic nerve, chiasm and electrophysiology may characterize retinal or postretinal pathway dysfunction and therefore help in early diagnosis. [source]