Effects of continuous and intermittent administration and inhibition of resorption on the anabolic response of bone to parathyroid hormone.

The role of resorption in the anabolic response of bone to parathyroid hormone (PTH) is not well understood. In contrast to the increase in bone mass induced by intermittent PTH in intact rats, continuous infusion of PTH into thyroparathyroidectomized (TPTX) rats failed to increase bone volume. The objective of this study were to determine if continuous infusions of low doses of PTH were anabolic in intact rats and if inhibition of resorption would enhance or block an anabolic action of PTH. Young male rats were treated with either continuous infusion or intermittent injections of hPTH-(1-34) for 12 days. In experiment 1, PTH, infused daily at 4 micrograms per 100 g, increased femur calcium and dry weight. Unlike infusion of 8 micrograms PTH, which did not alter bone mass, intermittent PTH at 8 micrograms was anabolic and increased bone mass by increasing trabecular thickness and number. Infusion of 16 micrograms induced hypercalcemia and death. In experiment 2, lower dose daily infusions of 0.25-4 micrograms PTH per 100 g did not increase bone mass. In experiment 3, in rats pretreated with dichloromethylene diphosphonate (Cl2MDP) to inhibit resorption and subsequently exhibiting decreased bone formation, PTH, irrespective of the method of administration, reversed the inhibitory effects of Cl2MDP on bone formation. Thus, intermittent and continuous PTH increase bone formation independently of effects on bone resorption, but only intermittent PTH increases bone mass consistently.     

Recombinant single‐chain antibodies against s‐Triazines

Recombinant antibody (RAb) technology is expected to play an essential role in future food and environmental immunoanalysis. The RAb approach is not yet, however, considered as a standard method, mainly due to technical reasons. In order to establish a feasible protocol for the production of hapten specific RAbs, the essential steps of the procedure are considered in detail, especially the polymerase chain reaction amplification of antibody coding genes and the utilization of immunomagnetic selection of phages displaying selective RAbs. The synthesis of functional recombinant single‐chain Fv against s‐triazine herbicides is used as an example. Expressed RAbs are characterized by immunoassay. Although RAb‐based calibration curves were shifted toward higher concentrations by one order of magnitude, the cross‐reactivity pattern of RAbs corresponded to the original monoclonal antibodies. Sequences of different RAb clones derived from the same hybridoma line only differed in a single silent mutation. This confirms the reliability of the RAb procedure.     

Hemispheric asymmetry: the effect of orientation on same different comparison

In a same-different comparison task, orientation affected “same” reaction times for left but not right visual-field presentations. This provided evidence that the “orientation effect” was due to spatial coding of memory representations in the right hemisphere, and that left hemisphere processing involves attention to orientationally invariant features.     

Distribution of intrarenal blood flow consequent to left atrial balloon inflation

The effects of inflation of a balloon within, and consequent distension of, the left atrium (LABI, left atrial balloon inflation) on total renal blood flow (RBF) and intrarenal blood flow distribution were measured and compared to values obtained from another group of dogs that were hemorrhaged (HEM) to the same level of hypotension as that produced by LABI, a mean systemic arterial pressure of 88 mm Hg. Kidney wt/kg, RBF/kg body wt, and urine flow were markedly reduced during the hemorrhage period in the HEM group when compared to values obtained during the experimental period for the LABI group. Data from the freeze-dissection (133Xe) analysis revealed that the percentage distribution of blood flow as renal outer cortical (OC) blood flow was less (26%) in the HEM group than in the LABI group (50%), this latter value being very similar to that of control dogs that experienced no hypotension (49%). LABI better maintains OC blood flow and urine flow when compared to HEM at the same systemic blood pressure, suggesting a role for cardiopulmonary receptors in reflex sympathetic control of renal blood flow distribution during hypotension.     

Cholesterol 25-hydroxylase on chromosome 10q is a susceptibility gene for sporadic Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by beta-amyloid (A beta) plaques, neurofibrillary tangles and the degeneration of specifically vulnerable brain neurons. We observed high expression of the cholesterol 25-hydroxylase (CH25H) gene in specifically vulnerable brain regions of AD patients. CH25H maps to a region within 10q23 that has been previously linked to sporadic AD. Sequencing of the 5' region of CH25H revealed three common haplotypes, CH25Hchi2, CH25Hchi3 and CH25Hchi4; CSF levels of the cholesterol precursor lathosterol were higher in carriers of the CH25Hchi4 haplotype. In 1,282 patients with AD and 1,312 healthy control subjects from five independent populations, a common variation in the vicinity of CH25H was significantly associated with the risk for sporadic AD (p = 0.006). Quantitative neuropathology of brains from elderly non-demented subjects showed brain A beta deposits in carriers of CH25Hchi4 and CH25Hchi3 haplotypes, whereas no A beta deposits were present in CH25Hchi2 carriers. Together, these results are compatible with a role of CH25Hchi4 as a putative susceptibility factor for sporadic AD; they may explain part of the linkage of chromosome 10 markers with sporadic AD, and they suggest the possibility that CH25H polymorphisms are associated with different rates of brain A beta deposition.     

Effects of memory consolidation on human hippocampal activity during retrieval

Day-to-day memories undergo transformation from short-term to long-term storage, a process called memory consolidation. Animal studies showed that memory consolidation requires protein synthesis and the growth of new hippocampal synapses within 24 h. To test for effects of memory consolidation in the human, we examined brain activation during the retrieval of information at 10 min and at 24 h following learning using functional magnetic resonance imaging (fMRI), an indirect measure of synaptic activity. Learning instructions were adjusted to yield a comparable retrieval quantity and retrieval quality at 10 min and 24 h after learning. The left hippocampal formation exhibited enhanced activity during the retrieval at the 24 h lag compared to the retrieval at the 10 min lag. Moreover, the activity in the left anterior hippocampal formation showed stronger correlations with retrieval quantity and retrieval quality at the 24 h lag than at the 10 min lag. This suggests that the relation between left anterior hippocampal activity and retrieval success became closer as consolidation progressed. These fMRI results in the human hippocampal formation may correspond to the neurobiological results in the animal hippocampal formation of a strengthening and growth of synaptic connections within 24 h.