Synthesis of adenosine triphosphate in isolated nuclei and intact cells

1. It has previously been demonstrated that nuclei isolated from normal and neoplastic lymphoid cells are capable of oxygen-dependent ATP synthesis. In this paper it is shown that also the corresponding intact cells can synthesize ATP under those conditions in which nuclei can synthesize ATP. 2. In nuclei isolated from liver, kidney, rhabdomyosarcoma and osteosarcoma, oxygen-dependent ATP synthesis could not be demonstrated. The cells isolated from these tissues or tumours could not synthesize ATP either. The alternatives that such nuclei lost their ability for oxidative phosphorylation during the isolation procedure or that the process does not occur in these nuclei were explored. 3. Janus Green B, a vital stain for mitochondria, was used as a differential inhibitor of mitochondrial and nuclear ATP synthesis in intact cells. 4. Oxidative phosphorylation in mitochondria isolated from cells that had been incubated with various concentrations of Janus Green B (1–10μm) was seriously uncoupled, whereas at these concentrations oxygen-dependent ATP synthesis in isolated nuclei and in isolated cells were only inhibited to a small extent. 5. The results suggest that oxygen-dependent ATP synthesis in isolated cells measured under `nuclear' conditions and in the presence of Janus Green B and Ca²⁺ is mainly due to nuclear oxygen-dependent ATP synthesis. The stimulation of cellular ATP synthesis by glucose was completely inhibited by Janus Green B. 6. It is tentatively concluded that the stimulation of ATP synthesis in isolated cells by glucose, which is not found in isolated nuclei, represents mitochondrial ATP synthesis, and nuclear and mitochondrial ATP synthesis can then be studied differentially in the intact cell. The possibility is considered that oxygen-dependent nuclear ATP synthesis is not a general property of cell nuclei.     

Chromosome aberration and environmental physical activity: Down syndrome and solar and cosmic ray activity, Israel, 1990–2000

The possibility that environmental effects are associated with chromosome aberrations and various congenital pathologies has been discussed previously. Recent advances in the collection and computerization of data make studying these potential associations more feasible. The aim of this study was to investigate a possible link between the number of Down syndrome (DS) cases detected prenatally or at birth yearly in Israel over a 10-year period compared with the levels of solar and cosmic ray activity 1 year before the detection or birth of each affected child. Information about 1,108,449 births was collected for the years 1990–2000, excluding 1991, when data were unavailable. A total of 1,310 cases of DS were detected prenatally or at birth—138 in the non-Jewish community and 1,172 in the Jewish population. Solar activity indices—sunspot number and solar radio flux 2,800 MHz at 10.7 cm wavelength for 1989–1999—were compared with the number of DS cases detected. Pearson correlation coefficients (r) and their probabilities (P) were established for the percentage of DS cases in the whole population. There was a significant inverse correlation between the indices of solar activity and the number of cases of DS detected—r=–0.78, P=0.008 for sunspot number and r=–0.76, P=0.01 for solar flux. The possibility that cosmophysical factors inversely related to solar activity play a role in the pathogenesis of chromosome aberrations should be considered. We have confirmed a strong trend towards an association between the cosmic ray activity level and the incidence of DS.     

Co-amoxiclav in recurrent acute otitis media: placebo controlled study.

OBJECTIVE--To determine the efficacy of coamoxiclav in children aged 6 months to 12 years with recurrent acute otitis media. DESIGN--A randomised double blind placebo controlled clinical trial. SETTING--General practice in the Netherlands. PATIENTS--121 children with recurrent acute otitis media, defined by onset of otalgia and otoscopic signs of middle ear infection within four to 52 weeks after the previous attack. Confirmation of diagnosis and randomisation was done by otolaryngologists. INTERVENTION--Oral co-amoxiclav or placebo in weight related doses for seven days. MAIN OUTCOME MEASURE--An irregular clinical course defined as the presence of otalgia or a body temperature greater than or equal to 38 degrees C, or both, after three days. RESULTS--Eleven (16%; 95% confidence interval 9% to 28%) children had an irregular course in the co-amoxiclav group and 10 (19%; 9% to 31%) in the placebo group (difference not significant). Age, dichotomised at 2 years, was the only significant prognostic factor for irregular course of the disease (odds ratio 5.9; 1.8 to 19.1). Among children aged below 2 years, 28% (4/14) in the co-amoxiclav group and 58% (7/12) in the placebo group had irregular courses. For children 2 years and older these percentages were 13% (7/52) and 7% (3/41). CONCLUSION--Children with recurrent acute otitis media are at greater risk of an irregular clinical course of the disease than children with a first episode of acute otitis media. Co-amoxiclav has no significant benefit over placebo in treating children over 2 years with acute otitis media.     

A historical perspective towards a non-invasive treatment for patients with atherosclerosis

The history of atherosclerosis and cardiovascular disease dates back to ancient times. From the teachings of Galen to the response-to-injury hypothesis of Russel Ross, we have now arrived at the concept of the vulnerable plaque. Next to the development of new treatment options for patients with atherosclerosis, also novel diagnostic imaging techniques have been developed to visualise the arterial wall and to characterise plaque composition. In this article the historical context of atherosclerosis and the attempts towards a noninvasive therapy for patients with atherosclerotic diseases are described. (Neth Heart J 2009;17: 140–5.)     

Coronary computed tomographic angiography as gatekeeper for new-onset stable angina

Patients with new-onset stable angina constitute a substantial part of the population seen by cardiologists. Currently, the diagnostic workup of these patients depends on the pre-test probability of having obstructive coronary artery disease. It consists of either functional testing for myocardial ischaemia or anatomical testing by using coronary computed tomographic angiography (CCTA) or invasive coronary angiography. In case the pre-test probability is > 5%, the current guidelines for the management of chronic coronary syndromes do not state a clear preference for one of the noninvasive techniques. However, based on the recently published cost-effectiveness analysis of the PROMISE trial and considering the diagnostic yield in patients with angina and nonobstructive coronary artery disease, we argue a more prominent role for CCTA as a gatekeeper for patients with new-onset stable angina.     

A finite element model of cell-matrix interactions to study the differential effect of scaffold composition on chondrogenic response to mechanical stimulation

Mechanically induced cell deformations have been shown to influence chondrocyte response in 3D culture. However, the relationship between the mechanical stimulation and cell response is not yet fully understood. In this study a finite element model was developed to investigate cell-matrix interactions under unconfined compression conditions, using a tissue engineered encapsulating hydrogel seeded with chondrocytes. Model predictions of stress and strain distributions within the cell and on the cell boundary were shown to exhibit space-dependent responses that varied with scaffold mechanical properties, the presence of a pericellular matrix (PCM), and the cell size. The simulations predicted that when the cells were initially encapsulated into the hydrogel scaffolds, the cell size hardly affected the magnitude of the stresses and strains that were reaching the encapsulated cells. However, with the inclusion of a PCM layer, larger cells experienced enhanced stresses and strains resulting from the mechanical stimulation. It was also noted that the PCM had a stress shielding effect on the cells in that the peak stresses experienced within the cells during loading were significantly reduced. On the other hand, the PCM caused the stresses at the cell-matrix interface to increase. Based on the model predictions, the PCM modified the spatial stress distribution within and around the encapsulated cells by redirecting the maximum stresses from the periphery of the cells to the cell nucleus. In a tissue engineered cartilage exposed to mechanical loading, the formation of a neo-PCM by encapsulated chondrocytes appears to protect them from initially excessive mechanical loading. Predictive models can thus shed important insight into how chondrocytes remodel their local environment in order to redistribute mechanical signals in tissue engineered constructs.     

A prevalent Y;15 translocation in the Ethiopian Beta Israel community in Israel

We describe 7 cases of abnormal karyotypes involving chromosomes Y and 15 in Ethiopian Beta Israel patients: 46,XX, der(15)t(Y;15)(q12;p12) and 46,XY,der(15)t(Y;15)(q12;p12). Six cases were incidentally found in amniocentesis performed for various indications; the indication for karyotyping in 1 case was recurrent abortions. To the best of our knowledge, this is the first report of this translocation in a specific ethnic group. We conclude that the derivative chromosome 15 with chromosome Y is probably a normal variant in Ethiopian Beta Israel occurring at an estimated frequency of 4/74 (5.4%). The prenatal diagnosis of this translocation in this population probably does not require further parental testing.