DNA sequence recognition by bis-linked netropsin and distamycin derivatives

The dihydropyridine receptor (DHPR), a voltage-gated L-type Ca2+ channel, and the Ca2+ release channel/ryanodine receptor isoform-1 (RyR1) are key molecules involved in skeletal muscle excitation-contraction coupling. We have reported age-related decreases in the level of DHPR expression in fast- and slow-twitch muscles from Fisher 344 cross Brown Norway (F344BNX) rats (Renganathan, Messi and Delbono, J. Membr. Biol. 157 (1997) 247-253). Based on these studies we postulate that excitation-contraction uncoupling is a basic mechanism for the decline in muscle force with aging (Delbono, Renganathan and Messi, Muscle Nerve Suppl. 5 (1997) S88-92). In the present study, we extended our studies to older ages and we intended to prevent or retard excitation-contraction uncoupling by restricting the caloric intake of the F344BNX rats from 16 weeks of age. Three age groups, 8-, 18-, and 33-month old caloric restricted rats, were compared with ad libitum fed animals. The number of DHPR and RyR1 and DHPR/RyR1 ratio (an index of the level of receptors uncoupling) in skeletal muscles of 8-month and 18-month rats was not significantly different in either ad libitum fed or caloric restricted rats. However, the age-related decrease in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in 33-month old ad libitum fed rats was absent in 33-month old caloric restricted rats. These results suggest that caloric restriction prevents age-related decreases in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in fast- and slow-twitch rat skeletal muscles.     

Plutonium anomalies in attic dust and soils at locations surrounding the Nevada Test Site

Attic dust and soil samples were collected during the Summer of 1996 and the Spring of 1997 in southern Nevada and southern Utah. Analysis of the samples for radiocesium and plutonium give activity ratios of radiocesium/plutonium that range from 0.7 +/- 0.1 to 27 +/- 2, well below the world-wide fallout ratio of 34 +/- 4 (as of 1 July 1997). This indicates anomalous plutonium throughout the region, including areas to the south of the Nevada Test Site (NTS), generally believed to have received only world-wide fallout. Safety tests and above-ground detonations that resulted in incomplete fission, conducted at the NTS during the 1950's and 1960's, are likely sources of this excess plutonium.     

Dietary fish oil enhances macrophage production of nitric oxide

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare but well-documented lesion of neuroectodermal derivation. Maturation of the neural elements has been reported only occasionally. We report a case of MNTI of the maxilla showing maturation of neural elements to ganglionic cells.     

Regression of established mouse leukemia by GM-CSF-transduced tumor vaccine: implications for cytotoxic T lymphocyte responses and tumor burdens

This study investigated the therapeutic effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on a mouse leukemia model. By using a retroviral vector, mouse GM-CSF cDNA was transduced into a highly tumorigenic T leukemia cell line, RL male 1. Injection of GM-CSF-secreting RL male 1 cells into syngeneic BALB/c mice elicited protective immunity in the animals, which could regress preestablished tumors introduced either by a subcutaneous or in an intravenous route. However, the therapeutic effects were less prominent in the mice inoculated with a large tumor load or in mice treated later. Winn tests further demonstrated that the splenocytes from the late-treated group conferred poorer protective effects in terms of reducing the growth of parental RL male 1 cells in naive mice than the splenocytes from the early-treated group. Nonetheless, upon stimulation in vitro, the activity of tumor-specific cytotoxic T lymphocytes (CTL) was comparable in the splenocytes of both groups of mice. Histological analysis also indicated that the CD8+ T cells appeared as early as 3 days following vaccination at the vaccine sites and at the tumor sites in both groups of mice. Above observations implied that the T cells in the animals bearing large tumors appeared to be in a state of suppression or anergy. Systematic histological analyses for 2 weeks provided further insight into various infiltrates at the vaccine sites and at the tumor sites in response to the inoculation of GM-CSF-secreting tumor vaccine.     

Indometofen causes biochemical changes in the blood cells characteristic for a radioresistant state of the body

The DNA and RNA contents, RNA/DNA ratio, and spontaneous and latex-induced oxidant activity indices of the whole blood were studied in the nitroblue tetrazolium test of mono- and polymorphonuclear blood leucocytes of intact dogs after injection of lipopolysaccharide pyrogenal. Significant changes in the above parameters were revealed for radioresistant (survived) and radiosensitive (lost) animals exposed to a subsequent prolonged gamma irradiation with a lethal dose of 7.64 Gy (LD75/45). Peroral introduction of 30 mg/kg indometofen (an indole analog of tamoxifen), which is a potential radioprotector, to dogs increased the survival rates of the irradiated dogs up to 93% and aided in the adaptive biochemical changes in the nuclear cell compartment of blood to induce a radioresistant status of the organism.     

Serological properties of HIV-1 isolates from the focus of an epidemic in the Gomel region of the Belarus Republic (1996)

Immunoreactivity of sera obtained in 1996 from HIV-1-infected intravenous narcomaniacs from an epidemic focus in Gomel region, Belarus, is studied with a panel of 10-16-component synthetic peptides simulating apical epitope of surface glycoprotein gp120 V3 loop of HIV-1 variants. Comparative analysis of resultant spectra with representative immunoreactivity spectra of sera from a sampling of HIV-1-positive sera collected in 1986-1997 in different regions of the former USSR demonstrated a high homogeneity of immunoreactivity spectra of sera from Gomel region. Serotypes of HIV-1 A/C variants circulating in populations of intravenous narcomaniacs in the focus in Gomel region in 1996 and in Southern and South-Eastern Ukraine in 1995-1996 are similar. This confirms a previous conclusion about the prevalence of A/C serotype among intravenous narcomaniacs in the former USSR.     

Long-term changes in excitability induced by protein kinase C activation in Aplysia sensory neurons

Protein kinases A (PKA) and C (PKC) play a central role as intracellular transducers during simple forms of learning in Aplysia. These two proteins seem to cooperate in mediating the different forms of plasticity underlying behavioral modifications of defensive reflexes in a state- and time-dependent manner. Although short- and long-term changes in the synaptic efficacy of the connections between mechanosensory neurons and motoneurons of the reflex have been well characterized, there is also a distinct intermediate phase of plasticity that is not as well understood. Biochemical and physiological experiments have suggested a role for PKC in the induction and expression of this form of facilitation. In this report, we demonstrate that PKC activation can induce both intermediate- and long-term changes in the excitability of sensory neurons (SNs). Short application of 4beta-phorbol ester 12,13-dibutyrate (PDBU), a potent activator of PKC, produced a long-lasting increase in the number of spikes fired by SNs in response to depolarizing current pulses. This effect was observed in isolated cell culture and in the intact ganglion; it was blocked by a selective PKC inhibitor (chelerythrine). Interestingly, the increase in excitability measured at an intermediate-term time point (3 h) after treatment was independent of protein synthesis, while it was disrupted at the long-term (24 h) time point by the general protein synthesis inhibitor, anisomycin. In addition to suggesting that PKC as well as PKA are involved in long-lasting excitability changes, these findings support the idea that memory formation involves multiple stages that are mechanistically distinct at the biochemical level.