Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival

Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cell migration through its cell surface receptors and by effecting changes in the physical environment. HA expression is frequently increased in malignant tumors, whereas its association with the invasive potential and patient outcome in breast cancer has not been reported. The localization and signal intensity of HA was analyzed in 143 paraffin-embedded tumor samples of human breast carcinoma using a biotinylated HA-specific probe. In the immediate peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HA, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-associated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox's multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were independent prognostic factors for overall survival. These results suggest that HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies.     

Cognitive functions in relation to MRI findings 30 years after traumatic brain injury

OBJECTIVE: The aim of the study was to relate cognitive effects of a remote traumatic brain injury (TBI) to MRI findings and severity of injury. METHOD: Sixty-one patients were assessed on average 30 years after a TBI of variable severity. A comprehensive cognitive test battery was used to evaluate memory, executive functions and cognitive overall impairment. Multiple regression analyses were used to examine the relationships between cognitive variables and MRI volumetric findings (the volumes of the hippocampus and the lateral ventricles) and local contusions on MRI. Also, the effect of injury severity on cognitive outcome was evaluated. RESULTS: Reductions in hippocampal volumes and lateral ventricular enlargement were significantly associated with impaired memory functions, memory complaints and executive functions. Of the MRI parameters used, the best predictor for cognitive outcome was the volume of the lateral ventricle. There was only a modest relationship between severity of injury and cognitive performance. CONCLUSIONS: The results show that long-term memory impairments after TBI are associated with MRI volumetric measures. This suggests that the degree of diffuse injury leading to atrophic changes is prognostically more important than the initial severity of TBI.     

Expression of CD 44 s, CD 44 v 3 and CD 44 v 6 in benign and malignant breast lesions: correlation and colocalization with hyaluronan

AIMS: To examine the expression of CD 44 s, CD 44 v 3 and CD 44 v 6 in breast lesions, and to correlate it with the expression of hyaluronan (HA). Methods and results: CD 44 expression was studied in 75 breast tissue samples, consisting of benign, premalignant and malignant breast lesions, using immunohistochemistry. CD 44 s, but not CD 44 v 3 or CD 44 v 6, was found in the stromal cells, and it was similar in benign and malignant tumours. In benign lesions CD 4 v 6 was detected in 20-30% of the ductal epithelial cells, while C 44 v 3 and CD 44 s were not expressed. CD 44 s, CD 44 v 3 and CD 44 v 6 were all up-regulated in the in situ carcinomas and invasive carcinomas. The level of CD 44 expression in carcinoma cells did not correlate with the type or differentiation of the tumours. CD 44 and HA expression levels were not closely linked in the benign or malignant breast lesions, because HA was overexpressed later in breast cancer progression than CD 44. However, in breast carcinomas CD 44 and HA positivity was often found in the same areas of the sections, and the dual staining confirmed actual colocalization of CD 44 s and HA in the same cells. Conclusions: CD 44 s, CD 44 v 3 and CD 44 v 6 are up-regulated earlier than HA in breast carcinoma progression, and in later stages they often colocalize with cell surface HA.     

The discrimination of and orienting to speech and non-speech sounds in children with autism

The present study aimed to find out how different stages of cortical auditory processing (sound encoding, discrimination, and orienting) are affected in children with autism. To this end, auditory event-related potentials (ERP) were studied in 15 children with autism and their controls. Their responses were recorded for pitch, duration, and vowel changes in speech stimuli, and for corresponding changes in the non-speech counterparts of the stimuli, while the children watched silent videos and ignored the stimuli. The responses to sound repetition were diminished in amplitude in the children with autism, reflecting impaired sound encoding. The mismatch negativity (MMN), an ERP indexing sound discrimination, was enhanced in the children with autism as far as pitch changes were concerned. This is consistent with earlier studies reporting auditory hypersensitivity and good pitch-processing abilities, as well as with theories proposing enhanced perception of local stimulus features in individuals with autism. The discrimination of duration changes was impaired in these children, however. Finally, involuntary orienting to sound changes, as reflected by the P3a ERP, was more impaired for speech than non-speech sounds in the children with autism, suggesting deficits particularly in social orienting. This has been proposed to be one of the earliest symptoms to emerge, with pervasive effects on later development.     

The effects of past and anticipated future downsizing on survivor well-being: an equity perspective

Worker well-being was examined as a function of past downsizing and expectations concerning future downsizing. Data from 1,297 Finnish workers were analyzed using analysis of variance and structural modeling analysis. Having experienced downsizing in the past or anticipating downsizing in the future was associated with elevated levels of inequity, which in turn were associated with elevated levels of psychological strain, cynicism, and absence. There were also direct effects of past/anticipated future downsizing on strain, cynicism, and absence, meaning that inequity only partly mediated the relationship between downsizing and well-being. Moreover, well-being varied as a function of type of downsizing.     

No variants in the cardiac actin gene in Finnish patients with dilated or hypertrophic cardiomyopathy

Background Dilated and hypertrophic cardiomyopathies are primary myocardial diseases that cause considerable morbidity and mortality. Although these cardiomyopathies are clinically heterogeneous, genetic factors play an important role in their etiology and pathogenesis. The defects in the cardiac actin (ACTC) gene can cause both cardiomyopathies. The aim of our study was to screen for variants in the ACTC gene in patients with dilated or hypertrophic cardiomyopathy from Eastern Finland. Materials and Methods Altogether, 32 patients with dilated and 40 patients with hypertrophic cardiomyopathy were included in the study. Commonly approved diagnostic criteria were applied, and secondary cardiomyopathies were carefully excluded. All 6 exons of the ACTC gene were amplified with polymerase chain reaction and screened for variants with single-strand conformation polymorphism analysis. Results and Conclusion We did not find any new or previously reported variants. Our results indicate that defects in the ACTC gene do not explain dilated cardiomyopathy or hypertrophic cardiomyopathy in subjects from Eastern Finland and confirm earlier results that the ACTC gene does not play an important role in the genetics of dilated or hypertrophic cardiomyopathies. (Am Heart J 2002;143:11-4.)     

Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age

Background: Characteristics related to decreased lung function and increased bronchial responsiveness after early childhood wheezing requiring hospitalization are not fully established.
Methods: Seventy-nine children with wheezing requiring hospitalization at age <2 years were prospectively followed up and re-investigated at age 5.6–8.8 years when the measurements of baseline lung function and bronchial responsiveness to exercise were performed.
Results: At early school age, 23% of children had decreased lung function, and 13% had increased bronchial responsiveness to exercise. Predictors of decreased lung function were maternal history of smoking during pregnancy (odds ratio [OR], 12.8; 95% confidence interval [CI]: 1.2–139.6), parental history of asthma (OR, 4.3; 95%CI: 1.1–17.1), and female gender (OR, 4.0; 95%CI: 1.2–13.7). Increased bronchial responsiveness was associated with rhinovirus infection-induced wheezing in infancy (OR, 6.5; 95%CI: 1.2–36.3), and early cat or dog exposure leading to sensitization (OR, 26.6; 95%CI: 1.3–525.2). Inhaled anti-inflammatory therapy was common in children with rhinovirus infection-induced wheezing in infancy ( n  = 13/19; P  = 0.001 vs children with other/no confirmed virus infection etiology for wheezing in infancy, n  = 16/60), which may have improved lung function and attenuated bronchial responsiveness in them.
Conclusions: After early childhood wheezing requiring hospitalization, one-fourth of children will have decreased lung function and one-eighth of children will show increased bronchial responsiveness at school age. Gender, heredity of asthma, and antenatal exposure to tobacco smoke are predictors of decreased lung function, whereas rhinovirus infection etiology of wheeze and early animal exposure leading to sensitization are associated with increased bronchial responsiveness later in childhood.     

Incomplete restoration of immobilization induced softening of young beagle knee articular cartilage after 50-week remobilization

The aim of this study was to characterize the biomechanical and structural changes in canine knee cartilage after an initial 11-week immobilization and subsequent remobilization period of 50 weeks. Cartilage from the immobilized and remobilized knee was compared with the tissue from age-matched control animals. Compressive stiffness, in the form of instant shear modulus (ISM) and equilibrium shear modulus (ESM) of articular cartilage, was investigated using an in situ indentation creep technique. The local variations in cartilage of glycosaminoglycan (GAG) concentration were measured with a microspectrophotometer after safranin O staining of histological sections. Using a computer-based quantitative polarized light microscopy method, collagen-related optical retardation, gamma, of cartilage zones were performed to investigate the collagen network of cartilage. Macroscopically, cartilage surfaces of the knee joint remained intact both after immobilization and remobilization periods. Immobilization caused significant softening of the lateral femoral and tibial cartilages, as expressed by ESM (up to 30%, p < 0.05). Remobilization restored the biomechanical properties of cartilage in the lateral condyle of tibia, but in the lateral condyle of femur ESM remained 15% below the control level (p = 0.05). The instant shear modulus was not changed either after immobilization or remobilization. The GAG content of the cartilage was slightly decreased after immobilization, especially in the superficial zone of cartilage, but the change was not statistically significant. After remobilization the intensity of safranin O content rose to control level. Neither immobilization nor remobilization had any effect on the gamma value of collagen fibril network either in the superficial or the deep zone at any of the test points. The changes of ESM were positively correlated with the alterations in GAG content of the superficial and deep zones after immobilization and remobilization. This confirms the key role of protoglycans in the regulation of the equilibrium stiffness of articular cartilage. As a conclusion, immobilization of the joint of a young individual may cause long-term, if not permanent, alterations of cartilage biomechanical properties. This may predispose joint to degenerative changes later in life.     

Senile dementia of the Alzheimer type treated with aniracetam: a new nootropic agent

Forty-four patients with senile dementia of the Alzheimer type were randomly allocated into double-blind treatment with either aniracetam (RO 13-5057) 1 g or placebo daily for 3 months. Neurological examinations were made before and after treatment and psychometric tests were performed before and after 1 month's and after 3 month's treatment. Treatment was interrupted due to occurrence of confusion in four cases in the aniracetam group and in one case in the placebo group. During treatment, an improvement was seen in several cognitive tests, especially those associated with memory, but this improvement occurred in the placebo as well as in the aniracetam-treated group. In clinical evaluation no difference was seen in efficacy between the two treatment groups.