Are proteasomes involved in the formation of the kinetochore?

Proteasomes catalyse the degradation of proteins responsible for the regulation of mitosis enabling the cell to complete cell division. We have studied the effect of an inhibitor of the chymotrypsin-like activity of the proteasome on the trilaminar structure of the kinetochore in HeLa cells. Whereas a role for the proteasome in the degeneration of the kinetochore was predicted, we found instead that the inhibitor strongly retarded kinetochore development. We observed different developmental stages of the kinetochore from the fibrous ball of a prekinetochore to the mature kinetochore in one cell. The data presented here support the proposition that proteasomes are involved in kinetochore formation.accepted for publication by H. C. MacgregorDedicated to the memory of Prof. Dr. Daniel Mazia, a fatherly friend.     

Evolutionary history or function? Which preponderates in the expression of the muscle mass of the thoracic limb in wild carnivorans?

Thoracic limbs are extremely versatile and exhibit informative characteristics about habits of the Carnivora order in the wild. Despite this relevance, comparative studies with quantitative variables on thoracic limb muscles are still scarce in carnivorans. The aims of this study were to measure the mass of the intrinsic muscles of the thoracic limb of neotropical species of the Carnivora order and to establish comparative conjectures. For this purpose, 39 thoracic limbs of 10 neotropical carnivorans species were dissected. The mass of each muscle was measured on a digital scale, muscles were grouped by function, and the mass average percentage that each functional group of muscles occupied in the thoracic limb was calculated. The data of the present study was added to that available in the literature for 22 other carnivoran species. Three groups of species were considered: Canidae, Musteloidea, and Feliformia. Comparatively, the eight canid species included in this analyses concentrate muscle mass proximally in the thoracic limb to prioritize essential cursoriality. The nine musteloids had more muscle mass in the distal muscles due to the demand for versatility and manual strength, and the 14 Feliformia species exhibited an intermediate trend. The analysis of clusters revealed a great overlap of the percentage distribution of muscle mass with the phylogeny previously established for carnivorans. It could be verified that the distribution of muscle masses meets the demand of the locomotor habits of the species up to a certain level, from which phylogeny begins to limit morphological adaptations.     

Can we expect progress in the treatment of fibrosis in the course of chronic pancreatitis?

Chronic pancreatitis (CP) is a necroinflammatory process characterized by loss of both exocrine and endocrine function. To date, the disease has been treated symptomatically. Real advances in CP management can be expected once the pathophysiology of the disease is elucidated and individual stages of its development are properly managed. A key role in the CP pathogenesis is played by activation of pancreatic stellate cells (PSCs) that cooperate with the remaining pancreatic cells. All these cells produce cytokines, growth factors, angiotensin and other substances, which paracrinally or autocrinally induce further, persistent activation of PSCs. The activated PSCs are capable of producing and modifying the extracellular matrix. An optimal therapeutic preparation should exert beneficial effects on all the above-mentioned phenomena observed in CP. The most promising treatment modalities include blocking of the renin-angiotensin system (RAS), activation of peroxisome proliferator-activated receptors gamma (PPAR-γ), influence on the remaining PSC signaling pathways, blocking of substances produced by activated PSCs, and antioxidants. The findings of many recent experimental studies are highly encouraging; however, their efficacy should be confirmed in well-designed clinical trials.     

What is the role of rituximab in the treatment of rheumatoid arthritis?

Rituximab is a monoclonal antibody against CD20 that was developed for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). Recent controlled trials have shown that B cell-targeted therapy with rituximab is effective in RA (which suggest that B lymphocytes may be critical in its pathogenesis of RA) and early exposure data suggest that the tolerability and safety profile of rituximab may be even better in RA than in NHL patients. Rituximab is generally well tolerated, with a low incidence of serious adverse events, including serious infections. Available evidence suggests that its clinical benefits depend on effective B cell depletion, and the fact that its novel mode of action leads to the depletion of B cells makes it distinct from other biological therapies for RA that target T cells and their related cytokines. Although complete peripheral B cell depletion is regularly seen in RA and other autoimmune diseases, especially systemic lupus erythematosus (SLE), incomplete depletion has been reported in a subset of patients, even after full dosing with rituximab.     

End of life in ICU--care of the dying or 'pulling the plug'?

This study, a modified subsection of the European ETHICUS study on End-of-Life (EOL) Decision Making in the Intensive Care Unit (ICU), examines the pattern of limiting futile life-sustaining therapies in an Irish ICU including the practice of withdrawing mechanical ventilation in anticipation of death. 1146 patients were admitted to the Mater Hospital, Dublin ICU from 1/9/1999 to 30/6/2000 and all 126 patients who died in ICU were included. EOL categories were prospectively defined (by Ethicus methodology) as cardiopulmonary resuscitation (CPR); brain death; withholding (WH); withdrawing (WD) life sustaining therapy and active shortening of the dying process (SDP). Complete data were obtained for 122 of the 126 patients who died during this period. 45 patients (36%) had therapy withheld, 40 (33%) had therapy withdrawn, 26 (21%) had unsuccessful CPR and 11 (10%) were Brain Dead. SDP was not performed. In total, 85 patients had a limitation of life sustaining therapy. CPR was the main therapy withheld (96% of WH/WD patients). Inotropic infusions were limited (WH or WD) in 40/85 (47%) of patients. Fluids, feeding and oxygen were rarely withdrawn (2.4%, 6%, 4.8% respectively). Twenty-two patients had two or more EOL decisions. Tracheal extubation or withdrawal of ventilation was less frequent (16.4%) but more common if a second EOL decision was made. No patient had sedation withdrawn or decreased. Eight patients of 85 (9%) had sedation increased. The study demonstrates that EOL decision making is common (69% of deaths and 7.4% of ICU admissions) in Ireland and demonstrates that the pattern of treatment limitation relates primarily to cardiovascular and other treatments and less to respiratory life sustaining treatment. Artificial nutrition and hydration were rarely withdrawn.     

What is the role of tropomyosin in the regulation of muscle contraction?

Journal of Muscle Research and Cell Motility -     

What is the role of infant banging in the development of tool use?

Throughout the first year, infants are known to engage in repetitive motor behaviors. The current study examines the changes in the hand trajectory of one such behavior, banging, during the second half-year and the implications of these changes for tool use development. Fourteen (7- to 14-month-old) infants were seated at a table and presented with a small wooden cube. Kinematic measurements of their banging movements were recorded at 240 Hz. Analyses revealed stable temporal characteristics of the hand trajectories within and across infants. Results further indicated that as infants became older, their hands moved more efficiently in straighter up-and-down trajectories, with developmental changes especially pronounced for upward excursions of the hand: Younger infants’ arm movements were less straight on the way up than down, but there was no difference in the straightness of the two movement phases for older infants. These changes with age may reflect improvements in overcoming constraints associated with gravity and/or in motor planning. Additionally, the angle at which infants hit the table became more perpendicular with age. Collectively, the reported changes lead to more efficient movements, better aim and improved force delivery, enabling spontaneous banging movements to become well suited for instrumental hammering and tool use, more generally, later in childhood.     

What happened in the origin of human consciousness?

At some point in its evolutionary history, our species Homo sapiens ceased to be a nonlinguistic, nonsymbolic organism, living in the world as presented to it by Nature, and instead began to exist in a world that it reconstructs in its own mind. Most scientists since Darwin have been content to explain this extraordinary transformation in human consciousness by the operation of natural selection. However, the human fossil and archaeological records indicate that modern human symbolic consciousness is not the culmination of the long trend that natural selection would predict. Instead, it shows that major change in the human past has been episodic and rare and that, as far as can be determined from the archaeological record, the passage from nonsymbolic to symbolic cognition is a recent event as well as an unprecedented one. So recent, indeed, that it significantly postdates the acquisition of modern human anatomy as expressed in skeletal structure. It, thus, appears most likely that the biological (neural) capacity underwriting the radically new behavioral mode arose as an incidental exaptation in the same process that produced the new skeletal structure of Homo sapiens, but that it lay unexpressed until it was "discovered" by means of a cultural innovation, plausibly the invention of language. As in the case of the modern anatomical structure, it appears that the new capacity was initially expressed in Africa and that its various behavioral potentials were sequentially discovered in a drawn-out process that is continuing today. An "accidental" origin of the human capacity helps understand why so many human behaviors have proven self-destructive and contradictory, a feature of our species that reductionist, selection-based scenarios are hard-put to explain.     

Evaluation of methods of surfactant administration in the delivery suite?

Surfactant administered in the delivery suite might prevent or reduce the severity of subsequent respiratory distress syndrome. This review describes the evidence for surfactant delivery methods with relationship to their relevance in the delivery suite. The techniques include delivery using a thin catheter with the first breath, by the intubation-surfactant extubation procedure, less invasive surfactant administration (LISA) technique, using a laryngeal mask airway (LMA), or by nebulisation. There have been few randomised trials that have evaluated outcomes using these techniques in the delivery suite, and these were early trials. Currently, practitioners favour use of nasal continuous positive airway pressure with early rescue surfactant. Whether prophylactic surfactant given by the LISA technique or other techniques, such as via a LMA in the delivery suite, is more beneficial merits testing. This will require appropriately designed randomised trials with long-term outcomes.     

Performance of the PROTIA? Allergy-Q? System in the Detection of Allergen-specific IgE: A Comparison With the ImmunoCAP? System

Purpose

The PROTIA™ Allergy-Q® enzyme immunoassay (EIA) is a recently developed screening assay for specific immunoglobulin E (sIgE) for multiple allergens. The ImmunoCAP® fluorescent EIA (FEIA) system is the most widely used method for sIgE detection. In this study, we evaluated the performance of the Allergy-Q® system compared to the ImmunoCAP® system.

Methods

We compared the 2 systems using sera from 260 Korean allergy patients suffering from asthma (26.5%), allergic rhinitis (42.3%), atopic dermatitis (67.7%), and food allergy (18.1%). We compared sIgE-measurement results for 7 inhalant allergens, 5 food allergens, and 4 microorganism allergens.

Results

Overall, 1,799 paired assay results were analyzed. Except mugwort and alternaria, most of the allergen-sIgE results showed intra-class correlation coefficients of >0.5. Inter-assay class associations were reliable for most allergens (gamma=0.858-0.987, P<0.001). Passing-Bablok regression analysis showed multiple differences in intercept and slope. The inter-method concordance was moderate to substantial for most allergens (κ=0.713-0.898, P<0.001).

Conclusions

The PROTIA™ Allergy-Q® EIA system exhibited good detection performance compared to the ImmunoCAP® FEIA system in Korean allergic patients. However, because of methodological differences between the 2 assays, careful clinical implication is required for the interpretation of Allergy-Q® EIA results.     

Malignant transformation in synovial chondromatosis of the knee?

Although it has been reported, malignant transformation of synovial chondromatosis is rare. We report a case of malignant transformation of synovial chondromatosis in a knee to a low-grade chondrosarcoma, which was treated with synovial excision and total knee replacement. We also present a literature review of the subject. The case illustrates that malignant transformation should be suspected in chronic cases with a sudden exacerbation of symptoms and that interpretation of histology in cartilage lesions is difficult. It also demonstrates that even when guided biopsy techniques are used, the sampling error of a needle biopsy in any large lesion is unavoidable.