A mechanistic view of the non-ideal osmotic and motional behavior of intracellular water

It is commonly assumed that essentially all of the water in cells has the same ideal motional and colligative properties as does water in bulk liquid state. This assumption is used in studies of volume regulation, transmembrane movement of solutes and electrical potentials, solute and solution motion, solute solubility and other phenomena. To get at the extent and the source of non-ideally behaved water (an operational term dependent on the measurement method), we studied the motional and colligative properties of water in cells, in solutions of amino acids and glycine peptides whose surface characteristics are known, and in solution of bovine serum albumin, hemoglobin and some synthetic polypeptides. Solutions of individual amino acids with progressively larger hydrophobic side chains showed one perturbed water molecule (structured-slowed in motion) per nine square angstroms of hydrophobic surface area. Water molecules adjacent to hydrophobic surfaces form pentagonal structural arrays, as shown by X-ray diffraction studies, that are reported to be disrupted by heat, electric field, hydrostatic pressure and phosphorylation state. Hydrophilic amino acids demonstrated water destructuring (increased motion) that was attributed to dielectric realignment of dipolar water molecules in the electric field between charge groups. In solutions of proteins, several methods indicate the equivalent of 2-8 layers of structured water molecules extending beyond the protein surface, and we have recently demonstrated that induced protein conformational change modifies the extent of non-ideally behaved water. Water self-diffusion rate as measured in three different cell types was about half that of bulk water, indicating that most of the water in these cells was slower in motion than bulk water. In different cell types the extent of osmotically perturbed water ranged from less that half to almost all of the intracellular water. The assumption that essentially all intracellular water has ideal osmotic and motional behavior is not supported by the experimental findings. The non-ideally of cell water is an operational term. Therefore, the amount of non-ideally behaving water is dependent on the characteristics of water targeted, i.e. the measurement method, and a large fraction of it is explainable in mechanistic terms at a molecular level based on solute-solvent interactions.     

Maintenance of ions, proteins and water in lens fiber cells before and after treatment with non-ionic detergents

The proportional odds model is illustrated in the analysis of two efficacy scales used in a phase II clinical trial involving 81 schizophrenic patients. The proportional odds model preserves the discrete, ordinal nature of one of the scales. The analysis of this data suggested that the relationship between the two scales is not captured by a linear proportional odds model. A linear model and a piecewise linear model for the explanatory variable were therefore compared using likelihood-based analyses. Residuals from both models were compared. Predicted probabilities for the ordinal categories were constructed from the estimated model. Extensions and limitations of the model for interpretation of other trials and for the planning of future trials are discussed.     

Bone loss after hip fracture is correlated to the postoperative degree of mobilisation

This study quantifies changes in bone mineral density (BMD) in the opposite hip and in both proximal tibiae and the correlation with the use of walking aids for patients with two types of hip fracture during the 1st year after surgery. In all, 26 women and 15 men aged 42-88 years (median 71 years) were included. Twenty-one patients had an intracapsular hip fracture (ICF) and 20 had an intertrochanteric fracture (ITF). All patients were treated with a dynamic hip screw. BMD was measured by dual X-ray absorptiometry (DXA; LUNAR, Wisconsin) within the 1st week after surgery and after 3, 6 and 12 months. Initial BMD of the non-fractured hip was significantly lower for both fracture groups compared with reference material. For both fracture types there was a significant decrease in BMD of the non-fractured hip and proximal tibia of the fractured leg during the first 3 months, which still persisted a year after surgery. Improved mobilisation between two examinations was positively correlated with changes in BMD of the proximal tibia of the fractured leg and the non-fractured hip.     

Effect of specific training on menstruation and bone strength]

Secondary amenorrhoea is found with increased incidence in female athletes performing hard endurance training, especially when combined with demands for a low body weight. The etiology is multifactorial, but the energy balance (energy intake) in relation to the amount and intensity of training probably plays a crucial role. Long-lasting amenorrhoea may reduce the bone mineral content, perhaps partly irreversibly, especially in the lumbar vertebrae in long-distance runners. In gymnasts and light-weight rowers with a similarly high incidence of amenorrhoea, a much less pronounced effect on the lumbar bone mineral content has been reported in a few, small studies, pointing to a possible positive influence of specific training. The finding of stress fractures in an amenorrhoeic athlete should lead to further evaluation of the bone mineral status.     

Synaptic organisation of neuropeptide-containing preganglionic boutons in lumbar sympathetic ganglia of guinea pigs

Within the lumbar sympathetic ganglia of guinea pigs, the endings of different populations of neuropeptide-containing preganglionic neurons form well-defined pericellular baskets of boutons around target neurons in specific functional pathways. We have used multiple-labelling immunofluorescence, confocal microscopy, and ultrastructural immunocytochemistry to investigate synaptic organisation within pericellular baskets labelled for immunoreactivity to calcitonin gene-related peptide (CGRP), substance P (SP), or the pro-enkephalin-derived peptide, met-enkephalin-arg-gly-leu (MERGL) in relation to their target neurons. Different functional populations of neurons, identified by their neurochemical profile, showed a significant degree of spatial clustering and predicted well the distribution of specific classes of pericellular baskets. Most of the boutons in a basket were completely surrounded by Schwann cell processes and did not form synapses. The synapses that were present were made mostly onto dendrites enclosed by the Schwann cell sheath surrounding the neuron within the basket. These dendrites probably originated from neurochemically similar neighbouring neurons. Nevertheless, some of the boutons in the baskets did form synapses with the cell body or proximal dendrites of the neuron they surrounded. Occasionally, cell bodies received a relatively high number of synapses and close appositions from boutons in a pericellular basket. Synaptic convergence of two immunohistochemically distinct types of preganglionic inputs was found in baskets of SP-immunoreactive or MERGL-immunoreactive, but not CGRP-immunoreactive, boutons. Taken together, our results show that the appearance of pericellular baskets is primarily due to the packing of the target neurons. The grouping of functionally similar classes of neurons with their pathway-specific projections of peptide-containing preganglionic neurons suggests that peptides could exert their effects in relatively well-defined zones within the ganglia.     

An alternate pathway for T cell development supported by the bone marrow microenvironment: recapitulation of thymic maturation

In the principal pathway of alpha/beta T cell maturation, T cell precursors from the bone marrow migrate to the thymus and proceed through several well-characterized developmental stages into mature CD4+ and CD8+ T cells. This study demonstrates an alternative pathway in which the bone marrow microenvironment also supports the differentiation of T cell precursors into CD4+ and CD8+ T cells. The marrow pathway recapitulates developmental stages of thymic maturation including a CD4+CD8+ intermediary cell and positive and negative selection, and is strongly inhibited by the presence of mature T cells. The contribution of the marrow pathway in vivo requires further study in mice with normal and deficient thymic or immune function.     

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group

The purpose of this study was to evaluate the correlation between alteration in telomere length and prognosis in patients with pathological stage I-II non-small cell lung cancer. We measured telomeric repeat length and telomerase activity by use of southern blot analysis of terminal restriction fragments and a non-radioactive ELISA-based assay, respectively. RESULTS: Alterations in TRF lengths were present in 17(29.8%) of 57 patients. Patients with altered TRF length had significantly shorter survival than did patients without (P = 0.0051). In multivariate analysis, only alteration in TRF length independently correlated with shortened survival (P = 0.0033).