ST/b and DBA/2 mice differ in brain alpha-bungarotoxin binding and alpha 7 nicotinic receptor subunit mRNA levels: a quantitative autoradiographic analysis

Inbred mouse strains vary in sensitivity to a number of behavioral and physiological effects produced by nicotine. Differences in sensitivity to nicotine are correlated with variance in the number of brain nicotinic receptors as measured in regionally dissected brain tissue. The studies reported here used quantitative autoradiography and in-situ hybridization methods to measure regional levels of alpha-bungarotoxin (alpha BTX) binding and alpha 7 mRNA levels. Two inbred mouse strains, ST/b and DBA/2, were compared because these strains differ maximally in sensitivity to nicotine-induced seizures and in alpha BTX binding measured in regional brain homogenates. The binding of alpha BTX was significantly greater in the St/b strain in 42 of 127 brain regions that were analyzed, and a trend towards increased binding was seen in many additional brain regions. The most consistent strain differences were found in hippocampal, thalamic and pontine nuclei. Strain differences in alpha 7 mRNA levels were also detected, but these were not as widespread as were the alpha BTX binding differences. The alpha 7 mRNA levels were significantly correlated with alpha BTX binding in both mouse strains which suggests that the strain differences in binding are related, in part, to the levels of alpha 7 mRNA.     

Veterinary practice and occupational health. An epidemiological study of several professional groups of Dutch veterinarians. I. General physical examination and prevalence of allergy, lung function disorders, and bronchial hyperreactivity

The prevalence of allergy, lung function disorders, and bronchial hyperreactivity was studied in 102 Dutch veterinarians, subdivided into five professional groups (predominantly working with either swine, cattle, poultry, companion animals, or as a non-practitioner). The mean age of the participants was 43 years; 6 participants were females. Twenty-two per cent of the participants were overweight, and relatively more non-practitioners than practitioners were overweight. Approximately 23% of the vets reported complaints of prolonged fatigue. The data suggest a relationship between complaints of prolonged fatigue and a more than average number of daily working hours. Only a small proportion of vets were sensitized against several allergens. There were no significant differences in prevalence of distinct lung function disorders or bronchial hyperreactivity between professional groups. It is hypothesized that the respiratory complaints (chronic coughing, chronic phlegm production, stuffed nose, sneezing) reported by the vets predominantly working in swine and/or poultry practice could be caused by irritation and/or inflammation of the first part of the trachea-bronchial tree that has no measurable and permanent consequences for changes in lung function or increased bronchial hyperreactivity. The results of a skin test against allergens and determination of allergen-specific IgE in blood indicated that the respiratory complaints were probably not related to allergy against the panel of allergens tested.     

Symmetry breaking and training from incomplete data with Radial Basis Boltzmann Machines

A Radial Basis Boltzmann Machine (RBBM) is a specialized Boltzmann Machine architecture that combines feed-forward mapping with probability estimation in the input space, and for which very efficient learning rules exist. The hidden representation of the network displays symmetry breaking as a function of the noise in the dynamics. Thus, generalization can be studied as a function of the noise in the neuron dynamics instead of as a function of the number of hidden units. We show that the RBBM can be seen as an elegant alternative of k-nearest neighbor, leading to comparable performance without the need to store all data. We show that the RBBM has good classification performance compared to the MLP. The main advantage of the RBBM is that simultaneously with the input-output mapping, a model of the input space is obtained which can be used for learning with missing values. We derive learning rules for the case of incomplete data, and show that they perform better on incomplete data than the traditional learning rules on a 'repaired' data set.     

Isolation of Shigella dysenteriae serotypes 11, 12, and 13 from patients with diarrhea in Bangladesh

Nine isolates of bacteria biochemically resembling Shigella dysenteriae but not belonging to the 10 recognized serotypes were isolated from patients with diarrhea in Bangladesh. Further studies suggested that two, one, and six isolates belonged to the recently recognized S. dysenteriae serotypes 11, 12, and 13, respectively.     

Mode of vascularization of control and basic fibroblast growth factor-stimulated prefabricated skin flaps

This study, using 62 rabbits, examines the rate and pattern of vascular outgrowth from a subcutaneously implanted vascular pedicle, how the newly formed vessels connect to preexisting skin vessels, and whether local application of basic fibroblast growth factor can accelerate the angiogenic process. When the femoral artery and vein of rabbits are implanted beneath the skin, angiogenesis from both the pedicle and small blood vessels within the adjacent skin begins within 3 days. Perfusion with India ink reveals connections between the pedicle and dermal vessels as early as 5 days after implantation of the pedicle. Provided the pedicle does not thrombose, skin flaps based on it may survive completely when elevated as early as 2 weeks after implantation. Flap survival depends on the development of a small number of vascular connections between vessels arising from the pedicle and preexisting dermal vessels. If elevation is delayed until 4 weeks after implantation a flap may survive even if its pedicle has thrombosed. Prolonged release of basic fibroblast growth factor adjacent to the pedicle significantly increases the survival of flaps elevated 1 week after implantation but does not alter the survival of flaps elevated at 2 and 4 weeks.     

Rapid tamoxifen-induced inactivation of an estrogenic response is accompanied by a localized epigenetic modification but not by mutations

Ethidium was found to be efficiently cross-linked to DNA by glyoxal. Kinetic studies showed that the rate of the cross-linking reaction is strongly dependent on the glyoxal concentration. Comparative studies using a series of phenanthridines and acridines showed that NH2 groups at both the 2 and 7 positions on the phenanthridine ring are necessary for efficient cross-linking. Studies using synthetic polydeoxynucleotides showed that the 2-amino group of guanine is absolutely required for cross-linking. Fluorescence contact energy transfer and relative viscosity experiments showed that the cross-linked drug remains intercalated into DNA. DNA gel electrophoresis and melting studies demonstrated that cross-linked ethidium does not dissociate the DNA double helix to single strands.     

Plasma and blood lead concentrations, lead absorption, and lead excretion in nonhuman primates

The effects of pH, temperature, block of energy production, calcium/calmodulin, protein phosphorylation, and cytoskeleton-disrupting agents (cytochalasin D, nocodazole) on the integrity of the membrane skeleton were studied in polarized MDCK cells. The intracellular distributions of alpha-fodrin, actin, and ankyrin were monitored by immunofluorescence microscopy. The membrane skeleton, once assembled, seemed to be quite stable; the only factors releasing alpha-fodrin from the lateral walls were the acidification of the cytoplasm and the depletion of extracellular calcium ions. Upon cellular acidification, some actin was also released from its normal location along the lateral walls and was seen in colocalization with alpha-fodrin in the cytoplasm, whereas ankyrin remained associated with the lateral walls. No accumulation of plasma membrane lipids was observed in the cytoplasm of acidified cells, as visualized by TMA-DPH. These results suggest that the linkages between the fodrin-actin complex and its membrane association sites are broken upon acidification. The pH-induced change in alpha-fodrin localization was reversible upon restoring the normal pH. Reassembly of the membrane skeleton, however, required temperatures above +20 degrees C, normal energy production, proper cell-cell contacts, and polymerized actin. Release of alpha-fodrin from the lateral walls to the cytoplasm was also observed upon depletion of extracellular calcium ions. This change was accompanied by the disruption of cell-cell contacts, supporting the role of proper cell-cell contacts in the maintenance of the membrane skeleton polarity. These results suggest that local alterations of the cytoplasmic pH and calcium ion concentration may be important in regulating the integrity of the membrane skeleton.     

Changes of the corneal endothelium after ultraviolet-B exposure in previously photokeratectomized eyes

The photorefractive effect of excimer lasers is based on an interaction between the 193-nm ultraviolet-C laser beam and the stromal chromophore molecules. Recently, in some patients an increase of subepithelial haze and a regression of refractive effect has been observed following suntanning (UV-B exposure). The aim of the study was to find out the possible endothelial damage caused by photoablation with increasing depth and the effect of subsequent UV-B exposure on previously photokeratactomized eyes. Altogether 12 chinchilla rabbits were treated. Four animals received a -5.0 D PRK; four animals a -15.0 D PRK and four animals a -30.0 D PRK treatment. The endothelial average number, size and variation were determined two weeks post-PRK. Three weeks following PRK, a half of the animals received a 1 J/cm2 ultraviolet-B radiation in a constant dermatological UV-chamber. The endothelial morphology was measured the same way with automated specular microscopy two weeks after UV-B irradiation. After PRK treatment there was no statistically demonstrable change in endothelial morphology. On the other hand, after UV-B radiation all eyes showed a decrease in endothelial number and an increase in size and variation. The ratio of hexagonality decreased, and endothelial rosette formation appeared. The early morphological changes resembled the physiological aging changes. Conditions (deep stromal photoablation, cumulative effect of suntanning or solarium treatments) may exaggerate the physiological aging processes leading to subsequent pleomorphism, polymegatism and cell loss. This may accelerate corneal dysfunction.     

Leukemic pleural effusion in B-cell prolymphocytic leukemia

BACKGROUND: Proinflammatory mediators that include tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-2 (MIP-2) and anti-inflammatory mediators such as interleukin-10 (IL-10) modulate the immune response to endotoxemia. IL-10 downregulates the production of TNF-alpha and MIP-2. Acute lung injury may occur secondary to neutrophil chemotaxis mediated by chemokine MIP-2. We studied the temporal relationship of TNF-alpha, MIP-2, and IL-10 in rat endotoxemia and correlation of MIP-2 concentrations with acute lung injury. METHODS: Ten ventilated rats were randomized to receive an intravenous infusion of 2 mg/kg Escherichia coli lipopolysaccharide (n = 6) or saline placebo (n = 4). Blood pressure was continuously monitored and arterial blood was obtained for lactate, blood gas, TNF-alpha, IL-10, and MIP-2 measurements at baseline, 2, 4, and 5.5 hours after LPS or saline infusion. RESULTS: Endotoxemia resulted in hypotension, lactic acidemia, and increased alveolar-arterial oxygen gradient (A-a O2 gradient) compared with the placebo group. TNF-alpha, MIP-2, and IL-10 levels were increased 2 hours after endotoxemia. Subsequently, TNF-alpha levels declined while IL-10 and MIP-2 levels remained elevated. Control rats had no significant increase in cytokine production at any time point. MIP-2 concentrations correlated with A-a O2 gradient, an indicator of lung injury (r = 0.56, p < 0.001). CONCLUSIONS: MIP-2, possibly released by TNF-alpha stimulation of macrophages, is associated with acute lung injury possibly by inducing neutrophil chemotaxis. IL-10 may exert its counter-inflammatory response by inhibiting the release of TNF-alpha in endotoxemia.