Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia.

A new haemoglobin with increased oxygen affinity, beta82 (EF6) lysine leads to threonine (Hb Rahere), was found during the investigation of a patient who was found to have a raised haemoglobin concentration after a routine blood count. The substitution affects one of the 2, 3-diphosphoglycerate binding sites, resulting in an increased affinity for oxygen, but both the haem-haem interaction and the alkaline Bohr effect are normal in the haemolysate. This variant had the same mobility as haemoglobin A on electrophoresis at alkaline pH but was detected by measuring the whole blood oxygen affinity; it could be separated from haemoglobin A, however, by electrophoresis in agar at acid pH. The raised haemoglobin concentration was mainly due to a reduction in plasma volume (a relative polycythaemia) and was associated with a persistently raised white blood count. This case emphasises the need to measure the oxygen affinity of haemoglobin in all patients with absolute or relative polycythaemia when some obvious cause is not evident.     

Abeta42 is essential for parenchymal and vascular amyloid deposition in mice

Considerable circumstantial evidence suggests that Abeta42 is the initiating molecule in Alzheimer's disease (AD) pathogenesis. However, the absolute requirement for Abeta42 for amyloid deposition has never been demonstrated in vivo. We have addressed this by developing transgenic models that express Abeta1-40 or Abeta1-42 in the absence of human amyloid beta protein precursor (APP) overexpression. Mice expressing high levels of Abeta1-40 do not develop overt amyloid pathology. In contrast, mice expressing lower levels of Abeta1-42 accumulate insoluble Abeta1-42 and develop compact amyloid plaques, congophilic amyloid angiopathy (CAA), and diffuse Abeta deposits. When mice expressing Abeta1-42 are crossed with mutant APP (Tg2576) mice, there is also a massive increase in amyloid deposition. These data establish that Abeta1-42 is essential for amyloid deposition in the parenchyma and also in vessels.     

Taxonomy and biological control: Neoseiulus cucumeris (Acari: Phytoseiidae), a case study

The predatory mite Neoseiulus cucumeris (Oudemans) (Acari: Phytoseiidae) is an important biological control agent of thrips and other small pests worldwide. Yet, despite its economic importance, this species is poorly defined taxonomically and cannot be reliably separated from other species on the basis of morphology alone. Neoseiulus cucumeris has been reported from Australia, although considerable confusion exists as to whether the Australian material is actually N. cucumeris or a presumed endemic species, Neoseiulus bellinus (Womersley). A morphological investigation of N. bellinus and several geographical 'strains' of N. cucumeris demonstrated that: (i) N. bellinus is a distinct species, the males of which can be morphologically separated from those of N. cucumeris , using setal and cheliceral lengths and number of teeth on the fixed digit; and (ii) N. cucumeris , or a morphologically identical species, is present in Australia. Despite behavioural differences, there are no significant morphological differences between the 'strains' of N. cucumeris . Biosystematic research is a more reliable method of species separation, and such a method is suggested for future work with phytoseiid mites.     

How effective are added constraints in improving TKR kinematics?

Newer designs of total knee arthroplasty (TKA), through the use of added degrees of constraint, attempt to provide a \"guided motion\" to restore more normal and predictable kinematics. Two such design philosophies are the posterior stabilised (PS) using a cam-post and the medial pivot (MP) concepts. Knee kinematics of 12 patients with a PS TKA, 13 subjects with a MP TKA and 10 normal subjects were compared. For kinematic assessment, patients underwent fluoroscopic assessment of the knee during a step-up exercise and deep knee bend. Fluoroscopic images were corrected for distortion and assessed using 3D model fitting to determine relative 3D motion, and a 2D method to measure the patellar tendon angle (PTA) as function of knee flexion. For the PS design the cam-post mechanism engaged between 70 degrees and 100 degrees flexion. Between extension and 50 degrees there was forward motion of the contact points. Beyond 60 degrees both condyles rolled moved posteriorly. The majority of the external rotation of the femur occurred between 50 degrees and 80 degrees . The PTA was lower than normal in extension and higher than normal in flexion. The MP exhibited no anterior movement throughout the rage of motion. The medial condyle moved minimally. The lateral contact point moved posteriorly from extension to flexion. The femur rotated externally throughout the range of flexion analysed. The PTA was similar to normal from extension to mid flexion and then higher than normal beyond to high flexion. The PS design fails to fully restrain paradoxical anterior movement and although the cam engages, it does not contribute significantly to overall rollback. The MP knee does not show significant anterior movement, the medial pivot concept appears to achieve near normal kinematics from extension to 50 degrees of knee flexion. However, the results show that at high flexion this design does not achieve normal knee kinematics.     

Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysiology

A computational model of mitochondrial metabolism and electrophysiology is introduced and applied to analysis of data from isolated cardiac mitochondria and data on phosphate metabolites in striated muscle in vivo. This model is constructed based on detailed kinetics and thermodynamically balanced reaction mechanisms and a strict accounting of rapidly equilibrating biochemical species. Since building such a model requires introducing a large number of adjustable kinetic parameters, a correspondingly large amount of independent data from isolated mitochondria respiring on different substrates and subject to a variety of protocols is used to parameterize the model and ensure that it is challenged by a wide range of data corresponding to diverse conditions. The developed model is further validated by both in vitro data on isolated cardiac mitochondria and in vivo experimental measurements on human skeletal muscle. The validated model is used to predict the roles of NAD and ADP in regulating the tricarboxylic acid cycle dehydrogenase fluxes, demonstrating that NAD is the more important regulator. Further model predictions reveal that a decrease of cytosolic pH value results in decreases in mitochondrial membrane potential and a corresponding drop in the ability of the mitochondria to synthesize ATP at the hydrolysis potential required for cellular function.