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.     

The characteristics of the clinical course and treatment of suppurative wounds of the abdominal wall after the removal of a destructively altered appendix

Under analysis are specific features of the clinical course and treatment of infectious complications of the abdominal wall wounds in 209 patients after destructive forms of appendicitis. The microflora of the purulent wound contained gram-negative bacteria in combination with anaerobic nonclostridial flora. The electrochemically activated solution of potassium chloride EHAR-anolit and the endoscopic method were used in complex treatment of the purulent wounds. The recommended method of treatment makes the period of healing the wounds shorter and improves the results of treatment.     

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.     

Characterisation of L-[3H]glutamate binding to fresh and frozen crude plasma membranes isolated from cerebral cortex of adult rats

Specific [3H]glutamate binding to fresh crude plasma membranes (CPMs) was compared with binding to frozen CPMs and the optimal conditions for the binding to frozen CPMs isolated from cerebral cortex of adult rats were determined. Freezing reduced [3H]glutamate binding (3.5-fold), and pre-incubation of previously frozen membranes followed by three washes increased binding (4.5-fold) when compared to fresh samples. CPMs washed once, pre-incubated at 37 degrees C and washed 3 times was adopted as the most adequate condition for the binding assay of frozen membranes. In a Cl(-)-containing medium, [3H]glutamate binding (Bmax=97.9 pmol/mg, Kd=349.68 nM) to this frozen CPM preparation was significantly displaced by excess quisqualic acid (QA) (65%), L-2-amino-4-phosphonobutyric acid (L-AP4) (35%), trans-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD) (25%) and alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) (25%). In a Cl(-)-free medium, binding (Bmax=44.14 pmol/mg, 311 nM) was significantly displaced by QA (45%), L-AP4 (25%), ACPD (25%), AMPA (25%), kainic acid (20%) and N-methyl-D-aspartate (15%).     

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.     

Hepatic oval cell activation in response to injury following chemically induced periportal or pericentral damage in rats

Administration of 2-acetylaminofluorene (2-AAF) given before partial hepatectomy (PHx) results in suppression of hepatocyte proliferation and stimulation of oval cell proliferation. Our objective in this study was to examine the oval cell response and associated alpha-fetoprotein (AFP) gene expression by combining 2-AAF with selective damage of centrilobular regions (carbon tetrachloride [CCl4]) or periportal regions (allyl alcohol [AA]). Centrilobular damage results in a more enhanced oval cell response and AFP gene expression than periportal damage. Conversely, more intense proliferation of intraportal bile duct epithelia was seen with 2-AAF/AA than with 2-AAF/CCl4. The oval cell response and AFP gene expression was ranked as 2-AAF/ CCl4 > or = 2-AAF/PHx > 2-AAF/AA. AFP mRNA expression was also examined in an acute AA and CCl4 injury. We found very little AFP gene expression compared with the 2-AAF/hepatic injury models. To see a true oval cell response, the hepatocytes must be inhibited from proliferating. In addition, the results presented with the 2-AA/AA model suggest that the periportal matrix may be as important as the cells that populate the area.