Radiation physics and radiobiology

Three quite general rules link radiation physics to radiobiology. They concern the dependence on linear energy transfer of relative biological effectiveness and of the cross section for cell killing, as well as the dependence of relative biological effectiveness on absorbed dose. These rules are accounted for in compound dual radiation action according to which damage in the nanometer domain depends linearly on dose with no dose rate dependence and on relative biological effectiveness that is limited to low values because of saturation. Energy concentration in the micrometer domain can cause large relative biological effectiveness in processes in which pairs of DNA lesions interact with quadratic dose dependence and dose rate dependence for low linear energy transfer radiations. Damage at both the nanometer and the micrometer level can cause observed effects and their relative contributions determine the maximum relative biological effectiveness at very low doses.     

Current problems of neutron radiobiology

The molecular organization, interactions, phase state and membrane-membrane interactions of model membranes containing cerebroside (GalCer), sulfatide (Sulf) and myelin basic protein (MBP) were investigated. Sulf shows a larger cross-sectional area than GalCer, in keeping with the lateral electrostatic repulsions in the negatively charged polar head group. The interactions of GalCer with different phospholipids are similar while those with Sulf depend on the phosphoryl choline moiety in the phospholipid. MBP induces a decrease of the phase transition temperature in both lipids but with Sulf this occurs at lower proportions of MBP. In mixtures of Sulf with phosphatidylcholine MBP induces phase separation among Sulf-rich and PC-rich domains. Extensive apposition of bilayers containing Sulf is induced by MBP while GalCer interferes with this process. Few membrane interactions proceed to bilayer merging or whole bilayer fusion and the glycosphingolipids help preserve the membrane integrity.     

The concept of synergism in radiobiology]

We have demonstrated previously that pemphigus vulgaris (PV)-IgG induces activation of phospholipase C (PLC), production of inositol 1,4,5-trisphosphate, and a rapid transient increase in [Ca2+]i in cultured human keratinocytes, leading to secretion of plasminogen activator and cell-cell detachment in cell culture. In the current study, to examine the involvement of protein kinase C (PKC) in the mechanism of blister formation in PV, we studied the PV-IgG-induced translocation of PKC isozymes from the cytosol to the particulate/cytoskeleton (p/c) fractions and the activation of PKC in human keratinocytes. Cells cultured in Eagle's minimum essential medium were incubated with PV-IgGs for 30 s, 1 min, 5 min, or 30 min. PV-IgG binding to the cell surface antigen (desmoglein III) induced translocation of PKC-alpha from the cytosol to the p/c fractions within 30 s, with a peak at 1 min that lasted at least 30 min. PKC-delta also was translocated within 1 min and reached a peak at 5 min but was reduced to basal levels at 30 min. Alternatively, PKC-eta translocation to the p/c fraction was induced slowly, taking more than 5 min, and was reduced to approximately half-maximum at 30 min, whereas PKC-zeta translocation reached a maximum at 30 s, rapidly returning to baseline by 5 min after PV-IgG stimulation. The total PKC activity in the p/c fraction also was increased after PV-IgG exposure, peaked at 1 min, and was sustained for at least 30 min. These findings suggest that a unique activation profile of PKC isomers may be involved in mediating the intracellular signaling events induced by PV-IgG binding to desmoglein III in cultured human keratinocytes.     

Benzodiazepines revisited

Glucagonoma is an endocrine tumor of almost exclusively pancreatic origin which is rarely associated with a clinical syndrome mainly characterized by migratory necrolytic erythema, hyperglycemia, weight loss, hypoaminoacidemia and anemia. Ten to 30% of the patients may present thromboembolic phenomenon, deep vein thrombosis and pulmonary embolism which often lead to the death of the patient. We report the case of a patient diagnosed with pancreatic glucagonoma the presentation of which consisted in episodes of repeated deep vein thrombosis without associated migratory necrolytic erythema.     

Sadism revisited

Sadism has been for a long time, among psychoanalytic and other writers, the subject of extensive theorizing and controversy. This paper takes a fresh look at the many dimensions (sexual, characterological, neurotic, psychotic, neurological) of this old aberrations.     

Cyclazocine revisited

Recently synthesized compounds which have long-term mu antagonist activity and short-term kappa agonist effects prevent self-administration of cocaine and morphine in rats. Cyclazocine, a compound synthesized in 1962 and studied in animals and man in the 1960's and in the early 1970's is a mu antagonist in rats and man and is a potent kappa agonist in both species. It also prevents self-administration of cocaine and morphine in rats. Although it produces unpleasant side effects in man, subjects become tolerant to these side effects but not to the antagonistic actions of the drug after prolonged administration.     

Recovery revisited

Recovery of mechanical properties during annealing of deformed metals has been modelled based on a microstructural representation comprising two elements, (i) the cell/subgrain structure (size δ) and (ii) the dislocation density (ρ) within the subgrains. These two microstructural elements are treated as independent internal state variables and the recovery of flow stress obtained by adding the time dependent contributions due to subgrain growth [σ ∝ 1/δ(t)] and dislocation network growth

. The growth of a dislocation network has been treated in terms of thermally activated glide, thermally activated cross-slip, climb and solute drag as rate-controlling mechanisms. Subgrain growth has been analysed in a manner analogous to normal grain growth, with climb of the boundary dislocations being the rate controlling mechanism. The model has successfully been applied in the interpretations of recovery observations in iron, aluminium and AlMg alloys. It follows from the theoretical treatment as well as from the analysis of experimental data that the characteristic logarithmic time dependence of low temperature recovery is the result of a reaction controlled either by thermally activated glide of jogged screw dislocations or by solute drag. It has been demonstrated that a mechanism based on thermally activated cross-slip does not apply in this context.     

Theophylline revisited

For over 50 years, theophylline has been used regularly for the management of chronic asthma. However, because of its perceived narrow therapeutic index and the fact that it has been considered a weak bronchodilator, the use of theophylline therapy has diminished. Furthermore, with the introduction of newer pharmacologic agents and recommendations in widely accepted guidelines, both nationally and internationally, have further contributed to its decreased use. For years, theophylline has not only been considered a bronchodilator, but for many clinicians, an agent that could be used to enhance respiratory muscle function and mucociliary clearance and act at the level of the central nervous system to enhance ventilation. These properties were felt to be potentially useful for patients with severe exacerbated asthma. Recent studies have suggested that theophylline therapy can play a beneficial role in the management of both chronic stable asthma and exacerbated disease treated in the emergency department setting. Furthermore, a growing body of evidence suggests that theophylline has certain antiinflammatory and immunomodulating properties, even at plasma concentration levels below the accepted therapeutic range. If this is true, then theophylline may act best as a controller medication in the management of asthma. Because of its low cost and its ease of administration, theophylline therapy should be revisited and discussed as not only a reliever of bronchospasm, but a controller of chronic asthma.     

Asylums revisited

The authors revisited Erving Goffman's Asylum (Saint Elizabeths Hospital) and found both the "institutionalization" and "secondary adjustment" phenomena he described 20 years ago. However, they question whether secondary adjustments necessarily follows institutionalization. They also express doubt that institutionalization should be condemned automatically and suggest that it may in fact be the approach of choice for some patients.     

Vesicorectostomy revisited

Between 1948 and 1959 vesicorectostomy, a permanent anastomosis between the bladder and rectum, was constructed in 7 male patients. Scattered reports of this procedure exist but none since 1959 and long-term followup has never been reported. we present long-term followup, including renal function, excretory urography and voiding cystorectography, and review the quality of life in the 7 patients. The most frequent complication was stenosis of the anastomosis. None of the patients in this series with normal preoperative upper tracts showed radiographic or chemical deterioration postoperatively. Since this procedure maintains urinary continence, does not disturb the normal physiology of the ureterovesical junction and minimizes urinary reabsorption its use should be considered in certain patients as an alternative method of urinary diversion.