Basic isoferritin and hypercalcaemia in renal cell carcinoma

A 63-year-old man with iron loss anaemia and hypercalcaemia was found to have a renal cell carcinoma. Despite the iron-deficient blood and bone marrow picture, the serum ferritin concentration was markedly raised. This was mainly due to a “basic isoferritin”. The serum parathormone concentration was normal. The serum ferritin and calcium concentrations returned to normal after the tumour was removed. We propose that the renal cell carcinoma cells in this patient secreted the basic isoferritin as well as humoral factor(s) responsible for hypercalcaemia.     

Polyglutamine-expanded androgen receptors form aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by the HDJ-2 chaperone

Spinal bulbar muscular atrophy is a neurodegenerative disorder caused by a polyglutamine expansion in the androgen receptor (AR). We show in transiently transfected HeLa cells that an AR containing 48 glutamines (ARQ48) accumulates in a hormone-dependent manner in both cytoplasmic and nuclear aggregates. Electron microscopy reveals both types of aggregates to have a similar ultrastructure. ARQ48 aggregates sequester mitochondria and steroid receptor coactivator 1 and stain positively for NEDD8, Hsp70, Hsp90 and HDJ-2/HSDJ. Co-expression of HDJ-2/HSDJ significantly represses aggregate formation. ARQ48 aggregates also label with antibodies recognizing the PA700 proteasome caps but not 20S core particles. These results suggest that ARQ48 accumulates due to protein misfolding and a breakdown in proteolytic processing. Furthermore, the homeostatic disturbances associated with aggregate formation may affect normal cell function.     

Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis

Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular disease that affects the aorta, carotid, coronary and pulmonary arteries. Previous molecular genetic data have led to the hypothesis that SVAS results from mutations in the elastin gene, ELN. In these studies, the disease phenotype was linked to gross DNA rearrangements (35 and 85 kb deletions and a translocation) in three SVAS families. However, gross rearrangements of ELN have not been identified in most cases of autosomal dominant SVAS. To define the spectrum of ELN mutations responsible for this disorder, we refined the genomic structure of human ELN and used this information in mutational analyses. ELN point mutations co-segregate with the disease in four familial cases and are associated with SVAS in three sporadic cases. Two of the mutations are nonsense, one is a single base pair deletion and four are splice site mutations. In one sporadic case, the mutation arose de novo. These data demonstrate that point mutations of ELN cause autosomal dominant SVAS.      

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L- lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.      

Active music therapy in Parkinson's disease: an integrative method for motor and emotional rehabilitation

BACKGROUND: Modern management of Parkinson's disease (PD) aims to obtain symptom control, to reduce clinical disability, and to improve quality of life. Music acts as a specific stimulus to obtain motor and emotional responses by combining movement and stimulation of different sensory pathways. We explored the efficacy of active music therapy (MT) on motor and emotional functions in patients with PD. METHODS: This prospective, randomized, controlled, single-blinded study lasted 3 months. It consisted of weekly sessions of MT and physical therapy (PT). Thirty-two patients with PD, all stable responders to levodopa and in Hoehn and Yahr stage 2 or 3, were randomly assigned to two groups of 16 patients each. We assessed severity of PD with the Unified Parkinson's Disease Rating Scale, emotional functions with the Happiness Measure, and quality of life using the Parkinson's Disease Quality of Life Questionnaire. MT sessions consisted of choral singing, voice exercise, rhythmic and free body movements, and active music involving collective invention. PT sessions included a series of passive stretching exercises, specific motor tasks, and strategies to improve balance and gait. RESULTS: MT had a significant overall effect on bradykinesia as measured by the Unified Parkinson's Disease Rating Scale (p < .034). Post-MT session findings were consistent with motor improvement, especially in bradykinesia items (p < .0001). Over time, changes on the Happiness Measure confirmed a beneficial effect of MT on emotional functions (p < .0001). Improvements in activities of daily living and in quality of life were also documented in the MT group (p < .0001). PT improved rigidity (p < .0001). CONCLUSIONS: MT is effective on motor, affective, and behavioral functions. We propose active MT as a new method for inclusion in PD rehabilitation programs.     

Early brain lesions and face-processing development

Studies of functional plasticity after pre- or perinatal brain damage can tell us whether the neural substrate normally involved in the development of a given ability is specific and, if so, when it becomes functionally specified and unique. Development of face processing was investigated in 5- to 17-year-old children who had a unilateral brain injury in the pre-, peri-, or postnatal period. In Studies 1 and 2, patients with a posterior injury involving the temporal regions exhibited a face-processing deficit that was independent of their age at test time. Even though differences were observed between the two hemispheres in face processing during infancy as well as in adults in cases of normal development, no clear differences between right and left injury were observed here in face-processing deficit. Poor postlesional face-processing plasticity seems to contrast with results of several studies on speech development after early unilateral injury. If the difference in the time window for postlesional plasticity between these two areas of competency is confirmed, it would suggest that the two kinds of abilities rely on neural cells which are sensitive to different plasticity factors.     

Expression of insulin-like growth factor II (IGF–II) in human hepatocellular carcinomas: An immunohistochemical study

Recent results obtained using molecular biology techniques have suggested a possible role for insulin-like growth factor II (IGF-II) in the pathogenesis of hepatocellular carcinoma (HCC). To investigate this phenomenon, a monoclonal anti-body was used against IGF-II to study 54 patients with HCC. The presence of HBsAg was also tested both in serum and liver tissue. A positive immunoreaction was found in 9/15 (60%) of the HCC arising in cirrhotic livers of patients who had serum markers for HBV (HBV+ positive patients). These results provide further evidence that HBV might play a role in the expression of IGF-II. In HCC of patients without any markers of HBV infection (HBV- negative patients), IGF–II was detected in 10/39 (25.6%) of the tumors, and in some benign neoplastic lesions. It was found not only in neoplastic cells but also in some dysplastic nodules. The speculation arises that IGF–II expression may play a role in some steps of hepato-carcinogenesis.     

Autosomal dominant inheritance of left ventricular outflow tract obstruction

Most nonsyndromic congenital heart malformations (CHMs) in humans are multifactorial in origin, although an increasing number of monogenic cases have been reported recently. We describe here four new families with presumed autosomal dominant inheritance of left ventricular outflow tract obstruction (LVOTO), consisting of hypoplastic left heart (HLHS) or left ventricle (HLV), aortic valve stenosis (AS) and bicuspid aortic valve (BAV), hypoplastic aortic arch (HAA), and coarctation of the aorta (CoA). LVOTO in these families shows a wide clinical spectrum with some family members having severe anomalies such as hypoplastic left heart, and others only minor anomalies such as mild aortic valve stenosis. This supports the suggestion that all anomalies of the LVOTO spectrum are developmentally related and can be caused by a single gene defect.