Residual radiation damage in the mouse foot after exposure to heavy particles

Mice receiving a first treatment with graded doses of various heavy charged particles (protons and heavy ions) to one of their hind legs were re-exposed to a fixed dose of x rays eight months later to study the "memory" of residual damage from the first treatment. No significant memory of the first radiation exposure was observed for acute skin rection. However, there is an indication of memory for foot deformity. The results do not seem to indicate any significant differences in memory after exposure to 60Co gamma rays compared with protons or heavy ions, if biological effectiveness of the doses is taken into consideration.     

Early intervention, time-limited, targeted pharmacotherapy of schizophrenia

A growing appreciation of the risks of long-term, continuous neuroleptic use in the aftercare of schizophrenic patients has led to a search for alternative strategies. The authors report their experiences with the clinical strategy of "targeted" medication, in which patients are followed drug free until prodromal signs of impending relapse appear. Medication is then initiated to abort the impending episode and discontinued when patients restabilize clinically. Preliminary experience suggests that control of schizophrenic symptomatology comparable to that obtained with maintenance drugs can be achieved with a marked reduction in medication use when the targeted strategy is applied in the context of a broad-based program of psychosocial intervention based on a comprehensive medical model.     

Atelosteogenesis I and boomerang dysplasia: a question of nosology

We report a patient whose clinical, radiologic and histopathologic findings are compatible with severe atelosteogenesis (AT-I). The patient is compared with previously reported cases of AT-I, as well as with patients reported as having "boomerang" dysplasia. We conclude that it is reasonable to consider AT-I and boomerang dysplasia as part of a spectrum, probably reflecting a common etiology. More and detailed clinical, radiologic and histopathologic reports are needed to further clarify the relationship of AT-II and AT-III in this family of skeletal dysplasias.     

The available niacin values of foods for rats and their relation to analytical values

A bioassay for niacin was developed using weight gain or "gain/food eaten" of young rats as the response measure. The best basal diet contained casein 70 and gelatin 65.5 g/kg together with supplementary tryptophan to a total of 0.97 g/kg and other amino acids to meet requirements. After a 4-day depletion period, rats gained ca. 1 g/day over the next 20 days on the basal diet alone, or ca. 7 g/day and 12 mg/kg added nicotinic acid. Test foods were added at two levels with diets adjusted to keep constant amino acid composition. The results were compared with chemical analyses for total niacin (i.e., in extracts prepared from samples digested with alkali) and for free niacin (using extracts made at neutral pH) with separation of nicotinic acid and nicotinamide on thin-layer chromatograms or Sephadex columns. Eight samples of mature cooked cereals, with their niacin largely in bound forms, gave rat assay values equivalent to ca. 35% of their total niacin content. Alkali-cooked tortilas, steamed sweet corn, beans and liver, with their niacin all in free form, gave assay values close to their total niacin content. Baked potatoes and peanut flour were intermediate in both respects.     

6-125I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) as a potential radio-halogenated anti-cancer agent: In vitro investigations and possible clinical implications

6-¹²⁵I-iodo-2-methyl-1,4-naphthoquinol bis (diammonium phosphate) (6-¹²⁵I-iodo-MNDP) has been synthesised and studied as the prototype of a class of potential radio-halogenated anti-cancer agents. The incorporated ¹²⁵I provides Auger electron radiations which behave like high LET radiations in the treatment of tumours, though the accompanying X- and -radiations make an undersirable contribution to the total body dose. The in vitro experiments reported show that 6-¹²⁵I-iodo-MNDP is selectively concentrated in the cells of some human malignant tumours by factor of about 15 to 20 or more in relation to the cells of normal origin studied. On the basis of dosimetric considerations and comparison with clinical treatment with tritiated methylnaphthoquinol diphosphate, practical dosage of 6-¹²⁵I-iodo-MNDP is suggested and clinical indications and safety of use are discussed. The types of tumour of particular interest are inoperable cases of carcinoma of the colon, carcinoma of the pancreas, malignant melanoma and osteosarcoma. Further investigations are in progress.Beit Memorial Fellow for Medical Research     

Extravasation of albumin in tissues of normal and septic baboons and sheep.

Extravasation of albumin was measured in the tissues of normal and septic baboons and sheep. A group of normal animals (4 baboons, 4 sheep) was anesthetized for 6 hr and then given radioactively labeled albumin and red blood cells intravenously. The labeled albumin and red blood cells were allowed to equilibrate for exactly 15 min, at which time the animals were deliberately killed. Volumes of distribution of labeled albumin and red blood cells were then determined in the lungs, heart, liver, spleen, brain, and skeletal muscle of the baboons and in the lungs, heart, liver, and spleen of the sheep. Another group of animals (6 baboons, 14 sheep) were made septic by infusing live Escherichia coli organisms. The animals were resuscitated and volumes of distribution of albumin and red blood cells determined as in the normal animals. The volume of distribution of albumin was greater than the volume of distribution of red blood cells in all tissues in both species, both in control animals and in septic animals, with the exception of the spleen and skeletal muscle of the baboons and the spleen of the sheep. That is, albumin extravasated readily in most of the tissues of the animals, even within only 15 min of equilibration. There was moderate but significant extravasation in the lungs, heart, and brain. There was marked extravasation in the liver. Extravasation tended to be more pronounced in the septic animals. With this extensive degree of albumin extravasation, administration of albumin to patients, especially septic patients, is unlikely to prevent edema except in the spleen and skeletal muscle.     

Antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC), definition of the "K cell" in the rat.

The nature and membrane characteristics of the "K cell" of antibody-dependent lymphocyte-mediated cytotoxicity (Ab-LMC) were investigated in a widely used rat model of transplantation. Treatment of sensitized effector cell populations with anti-immunoglobulin and complement eliminated K cell cytotoxicity without diminishing the component of T cell-mediated injury. EA and EAC depletion experiments, although demonstrating no loss of K cell cytotoxicity after removal of complement receptor-bearing lymphocytes, produced a marked abrogation of cytotoxicity following the removal of the Fc receptor-bearing lymphocyte pool. Studies on phagocytic properties showed K cell activity to be shared by an adherent as well as a nonadherent cell population. Thus, the Fc receptor emerged as the only constant surface marker of the rat K cell in Ab-LMC.     

Ortho-substituted PCBs kill thymocytes.

The effects of exposure of acutely dissociated rat thymocytes to various polychlorinated biphenyl (PCB) congeners were examined using flow cytometry. Non-planar, ortho-substituted congeners caused a rapid cell death at low micromolar concentrations, while coplanar, dioxin-like congeners at the same concentration were without significant effect. The most potent of the congeners studied was PCB 52 (2,2',5,5'-tetrachlorobiphenyl), which had an IC50 of 3.96 microM at 20 min. Prior to loss of viability there was a decrease in mitochondrial membrane potential Delta Psi m, an accumulation of intracellular calcium, and a progressive leakiness of the plasma membrane. Application of PCB 52 in calcium-free medium reduced the calcium accumulation, but did not reduce cell death. Agents that depolarized mitochondria also did not induce the same degree of cell death caused by PCB 52. Cyclosporin A, which prevents opening of the mitochondria permeability transition channel, protected against cell death but did not protect against mitochondrial depolarization or calcium accumulation. Rapamycin and FK 506 at high concentration provided partial protection against cell death. These observations indicate that the ortho-substituted PCB 52 disrupts plasma, mitochondrial and endoplasmic reticulum membranes. We hypothesize that PCB 52 incorporates into lipid bilayers and with its bulky, three-dimensional ortho-substituted congener structure disrupts membrane function to a greater degree than coplanar congeners.