The role of the autonomic nervous system in regulating the excretory function of the stomach in irradiated dogs

Dogs and rats were exposed to gamma/neutron- and X-radiation. The anterior part of dog's stomach was exposed to 10 Gy and 13 Gy respectively; rats were subjected to whole-body irradiation with absolutely lethal doses. Prior to irradiation, various parts of the vegetative nervous system of both types of animals were "switched off" pharmacologically. In addition to clinical investigation of radiation sickness, the excretory function of the stomach was studied by the excretion of intravenously injected neutral red. The "switching-off" of the parasympathetic nervous system prior to irradiation stabilized the excretory processes in the stomach, increased the resistance of animals, and, vice versa, the "switching-off" of the sympathetic nervous system destabilized the excretory processes and decreased the resistance of the organism.     

Graft-versus-host reaction following granulocyte transfusion from a normal donor (author's transl)]

Graft-versus-Host disease following the transfusion of leukocytes from normal donor occured during remission-reinduction therapy in a 5 years old girl with acute lymphocytic leukemia. The clinical picture consisting of rash, diarrhea and somnolence was congruent with the diagnosis. Graft-versus-Host disease was confirmed by histology of skin biopsy and exclusion of other causes. The child survived the disease. We recommend the irradiation of leukocyte concentrates before transfusion.     

Radiation physiology of higher nervous activity: results and perspectives

Reflex forming and stabilization, the typological peculiarities of the experimental animals' higher nervous activity were discussed. The problems of the central nervous system functional reactions to irradiation in small doses, the chronic irradiation in particular, influence to higher nervous activity of heavy particles irradiation and neurochemical mechanisms of the disturbances in the central nervous system require further experimental investigations.     

Irradiation potentiation of cellular transfer of EAE: time course and locus of effect in irradiated recipient Lewis rats.

Further studies of the potentiating effect of 500 rads total body irradiation on cellular transfer of experimental allergic encephalomyeliatis (EAE) in Lewis rats have revealed two findings bearing on underlying mechanisms. First, the effect is transitory, potentiation of disease being observed in recipients irradiated 1 or 4 days before transfer of syngeneic sensitized donor lymphoid cells but not among animals irradiated 7 or 14 days before cell transfer. Second, lead shielding selectively excluding the central neuraxis from irradiation results in relatively little augmentation of EAE compared to that observed in non-shielded irradiated animals. We believe irradiation potentiation of EAE results from transitory alterations in central nervous system target tissue rendering it more vulnerable to host immunologic attack.     

The dynamics of the rats higher nervous activity disturbances after total influence of electrons and gamma-rays in doses 5-100 Gy

The dynamics of using of stabilized motor defensive conditioned reflex of active avoidance in "shuttle-box" in rats after total influence of high energy electrons and of gamma-rays in doses 5-100 Gy were investigated. The quality structure of higher nervous activity disturbances after the influence of these kinds of ionizing radiation was identical. Therefore the tendency to disturbances aggravating after the electron radiation influence in the periods of the initial depression and of relatively normalization was revealed, especially after the irradiation in dose 50 Gy. The effective compensation of the functional disturbances in the central nervous system at the first 5-10 min after irradiation was after influence of electron radiation in doses about 30 Gy and after the influence of gamma-radiation in doses about 50 Gy. The irradiation of rats in doses 10 Gy and 5 Gy caused qualitative different dynamics of radiation disturbances in rats higher nervous activity. The differences in rats higher nervous activity after influence of electron and of gamma-radiation in these doses did not manifest distinctly.     

Effect of microwave radiation on regional blood flow and tissue oxygenation in the brain

The effect of irradiation of the central nervous system by microwaves (MW) at a frequency of 2450 MHz and power 5-40 W on the regulation of cerebral circulation and oxygen supply to the nervous tissue were studied in rabbits. Local irradiation of the exposed cerebral cortex resulted in hyperemia and hyperoxia in the zone of exposure induced by the hyperthermal effect of MW. When the region of the medulla oblongata was irradiated even with low MW power (not leading to hyperthermia), the local circulation and oxygen tension increased in the whole brain, apparently due to the impairment of the regulation of the cerebral blood flow and oxygen supply to the brain tissue.     

Sympathetic hyperfunction causes increased sensitivity of the autonomic nervous system to whole-body X irradiation

Although the etiology of radiation sickness is still unknown, disturbance of the autonomic nervous system is suggested to be a factor. This study was designed to compare the radiosensitivity of spontaneously hypertensive rats possessing sympathetic hyperfunction and control Wistar-Kyoto rats, and to analyze the effects of radiation on the autonomic nervous system in both strains. After a 7.5-Gy dose of whole-body X irradiation, the blood pressure decreased significantly at 8 h and 2 days in the spontaneously hypertensive rats, but not in the Wistar-Kyoto rats. Epinephrine levels in the adrenal gland of spontaneously hypertensive rats decreased at 4, 8 and 24 h, unlike the Wistar-Kyoto rats. Radiation evoked a stronger increase in norepinephrine in the jejunum and colon of spontaneously hypertensive rats than in Wistar-Kyoto rats. Acetylcholine levels in the jejunum of spontaneously hypertensive rats decreased, in contrast to the increase in Wistar-Kyoto rats within 24 h after irradiation. The survival rate of spontaneously hypertensive rats was lower than that of Wistar-Kyoto rats and weight loss, appetite loss and morphological changes in the jejunum were greater in spontaneously hypertensive rats than in Wistar-Kyoto rats after irradiation. These results indicated that X irradiation caused greater activities in autonomic nervous function and severe radiation injury in spontaneously hypertensive rats. Sympathetic hyperfunction may be associated with a higher sensitivity to radiation, including radiation injury and radiation sickness.     

Microwave treatment of intracerebral l1210 leukemia: Schedule-dependent partial reversal of the effects of methotrexate

One-GHz microwave (MW) irradiation at a power density of 5 mW/cm² was combined with methotrexate (MTX) in an attempt to treat more effectively central nervous system (CNS) L1210 leukemia in DBA/2J mice. When mice with CNS leukemia were treated with the combination of MW and MTX, there was no improvement in survival compared with a group of animals treated with MTX alone; however, the group that received MTX before the MW exposure had a significantly reduced survival time compared with the group treated with MTX alone or with the group to which MTX was administered after MW.     

Postradiation changes in the systems of active transport of ions in the CNS. Energy requirements for active transport

A study was made of the effect of irradiation with a superlethal dose of 9.288 C/kg on oxidative phosphorylation in morphologically and functionally different parts of the central nervous system. The CNS-syndrome was shown to develop against the background of a pronounced injury to energy processes in the brain. It is supposed that the impairment of the energy supply of active ion transport systems plays an important role in the dysfunction of the brain induced by high-level radiation.     

Adaptation of the gymnosperms to the conditions of irradiation in the Chernobyl zone: from morphological abnormalities to the molecular genetic consequences

The most suitable plant indicator targets for radiation pollution biomonitoring are conifers, because they have high radiosensitivity. Previously accumulated information about the genetic nature of morphological abnormalities in gymnosperms, induced by acute and chronic irradiation in the exclusion zone of the Chernobyl nuclear power plant, are briefly considered in this review. Since an additional number of important research results appeared in the last decade that are dedicated to the analysis of molecular biological and molecular genetic effects of chronic irradiation on the coniferous plants growing in the exclusion zone of the Chernobyl disaster, all these data are also analyzed in the current review.     

Decreased weight, DNA, RNA and protein content of the brain after neutron irradiation of the 18-day mouse embryo

Pregnant mice were irradiated with 0.5 Gy fission neutrons on the eighteenth day of their gestation. The average litter size at birth was unchanged but mortality increased 5-6 fold in the first 3 days. The irradiated mice were the same weight as control mice at birth but showed a progressively increasing weight deficiency up to at least 36 days as compared to controls. Brain weight was 37, 45 and 25 per cent less in 2-, 3- and 52-week old irradiated animals, respectively, and the ratio of brain weight to body weight was 25, 27 and 13 per cent less. The concentrations of DNA, RNA and protein (mg/g wet tissue) were the same in irradiated and control mice in both brain and liver at all three ages. Total DNA, RNA and protein contents of whole brain after irradiation were 56-75 per cent of the control levels. No definite decrease was observed in liver. Histological study at 6 hours after irradiation showed nuclear pyknosis in the central nervous system from definite to very severe according to the part examined. It is concluded that damage to the central nervous system of the 18-day mouse foetus after neutron irradiation is mainly due to killing and/or inhibition of the differentiation of neuroblasts.     

Symptomatic epilepsy associated with intracranial calcifications in children with acute lymphoblastic leukemia (ALL)

Acute and long-term sequels of central nervous system (CNS) prophylaxis with irradiation and intrathecal chemotherapy in children suffering from acute lymphoblastic leukemia (ALL) include vasculopathies, leucoencephalopathies, intracranial calcifications, intellectual and neurological impairment. We report two children at the age 5 and 8 years who manifested partial motor or complex seizures and intracranial calcifications 2-4 years after the diagnosis of ALL had been established. The occurrence of these disorders was much earlier than reported in the literature. Both children received prophylactic CNS treatment with irradiation and intrathecal methotrexate (MTX). Their brain CT scans and EEG had been normal before the first epileptic seizure was registered. Children are now seizure free on carbamazepine, and a boy with complex partial and myoclonic seizures is also on valproate and vigabatrine. Symptomatic epilepsy associated with intracranial calcifications and persisting EEG changes might occur as side effects of ALL treatment.     

Genetic analysis of disease subtypes and sexual dimorphisms in mouse experimental allergic encephalomyelitis (EAE): relapsing/remitting and monophasic remitting/nonrelapsing EAE are immunogenetically distinct

Experimental allergic encephalomyelitis (EAE) is the principal animal model of multiple sclerosis (MS), the major inflammatory disease of the central nervous system. Murine EAE is generally either an acute monophasic or relapsing disease. Because the clinical spectrum of MS is more diverse, the limited range of disease subtypes observed in EAE has raised concern regarding its relevance as a model for MS. During the generation of a large F2 mapping population between the EAE-susceptible SJL/J and EAE-resistant B10.S/DvTe inbred lines, we identified four distinct subtypes of murine EAE resembling clinical subtypes seen in MS. We observed acute progressive, chronic/nonremitting, remitting/relapsing, and monophasic remitting/nonrelapsing EAE. An additional subtype, benign EAE, was identified after histologic examination revealed that some mice had inflammatory infiltrates of the central nervous system, but did not show clinical signs of EAE. Genome exclusion mapping was performed to identify the loci controlling susceptibility to each disease subtype. We report three novel EAE-modifying loci on chromosomes 16, 7, and 13 (eae11-13, respectively). Additionally, unique loci with gender-specific effects govern susceptibility to remitting/relapsing (eae12) and monophasic remitting/nonrelapsing (eae7 and 13) EAE.     

Demonstration of the activity of a rhesus-positive antigen in the erythrocytes of rhesus-negative donors and an increase in the expression of ABO system antigens after ultraviolet irradiation of the blood

UV irradiation (254 nm) in doses increasing erythrocyte (Er) hemolysis by 5 to 32% was found to stimulate the agglutination activity of ABO and Rhesus (Rh) system antigens. The stimulation effect was the higher the lower the antigen activity before irradiation. In the Rh-negative (Rh-)-Er, irradiation induced the Rh0(D)-like antigen specific activity suggesting that this antigen may be present in the Rh--Er membrane. Expression of Rh0(D)-antigen in Rh--Er, stimulation of its activity in Rh-positive cells, and activation of ABO system antigens may result from photo-chemical destruction of the outer membranous layer of the ER.     

Nervous system development of the sea cucumber Stichopus japonicus

The nervous system development of the sea cucumber Stichopus japonicus was investigated to explore the development of the bilateral larval nervous system into the pentaradial adult form typical of echinoderms. The first nerve cells were detected in the apical region of epidermis in the late gastrula. In the auricularia larvae, nerve tracts were seen along the ciliary band. There was a pair of bilateral apical ganglia consisted of serotonergic nerve cells lined along the ciliary bands. During the transition to the doliolaria larvae, the nerve tracts rearranged together with the ciliary bands, but they were not segmented and remained continuous. The doliolaria larvae possessed nerves along the ciliary rings but strongly retained the features of auricularia larvae nerve pattern. The adult nervous system began to develop inside the doliolaria larvae before the larval nervous system disappears. None of the larval nervous system was observed to be incorporated into the adult nervous system with immunohistochemistry. Since S. japonicus are known to possess an ancestral mode of development for echinoderms, these results suggest that the larval nervous system and the adult nervous system were probably formed independently in the last common ancestor of echinoderms.     

Late effects of radiation on the central nervous system: role of vascular endothelial damage and glial stem cell survival

Selective irradiation of the vasculature of the rat spinal cord was used in this study, which was designed specifically to address the question as to whether it is the endothelial cell or the glial progenitor cell that is the target responsible for late white matter necrosis in the CNS. Selective irradiation of the vascular endothelium was achieved by the intraperitoneal (ip) administration of a boron compound known as BSH (Na(2)B(12)H(11)SH), followed by local irradiation with thermal neutrons. The blood-brain barrier is known to exclude BSH from the CNS parenchyma. Thirty minutes after the ip injection of BSH, the boron concentration in blood was 100 microg (10)B/ g, while that in the CNS parenchyma was below the detection limit of the boron analysis system, <1 microg (10)B/g. An ex vivo clonogenic assay of the O2A (oligodendrocyte-type 2 astrocyte) glial progenitor cell survival was performed 1 week after irradiation and at various times during the latent period before white matter necrosis in the spinal cord resulted in myelopathy. One week after 4.5 Gy of thermal neutron irradiation alone (approximately one-third of the dose required to produce a 50% incidence of radiation myelopathy), the average glial progenitor cell surviving fraction was 0.03. The surviving fraction of glial progenitor cells after a thermal neutron irradiation with BSH for a comparable effect was 0.46. The high level of glial progenitor cell survival after irradiation in the presence of BSH clearly reflects the lower dose delivered to the parenchyma due to the complete exclusion of BSH by the blood-brain barrier. The intermediate response of glial progenitor cells after irradiation with thermal neutrons in the presence of a boron compound known as BPA (p-dihydroxyboryl-phenylalanine), again for a dose that represents one-third the ED(50) for radiation-induced myelopathy, reflects the differential partition of boron-10 between blood and CNS parenchyma for this compound, which crosses the blood-brain barrier, at the time of irradiation. The large differences in glial progenitor survival seen 1 week after irradiation were also maintained during the 4-5-month latent period before the development of radiation myelopathy, due to selective white matter necrosis, after irradiation with doses that would produce a high incidence of radiation myelopathy. Glial progenitor survival was similar to control values at 100 days after irradiation with a dose of thermal neutrons in the presence of BSH, significantly greater than the ED(100), shortly before the normal time of onset of myelopathy. In contrast, glial progenitor survival was less than 1% of control levels after irradiation with 15 Gy of thermal neutrons alone. This dose of thermal neutrons represents the approximate ED(90-100) for myelopathy. The response to irradiation with an equivalent dose of X rays (ED(90): 23 Gy) was intermediate between these extremes as it was to thermal neutrons in the presence of BPA at a slightly lower dose equivalent to the approximate ED(60) for radiation myelopathy. The conclusions from these studies, performed at dose levels approximately iso-effective for radiation-induced myelopathy as a consequence of white matter necrosis, were that the large differences observed in glial progenitor survival were directly related to the dose distribution in the parenchyma. These observations clearly indicate the relative importance of the dose to the vascular endothelium as the primary event leading to white matter necrosis.     

Regulation of lipid oxidation and structural state of the nuclear membrane after the irradiation of tumor-bearing animals

Changes of antioxidative activity (AOA), lipid composition and microviscosity of different membrane regions in tumor cell nuclei and in the liver of tumor-host with Ehrlich ascite carcinoma (EAC) after irradiation were studied. On the basis of the obtained data the analysis of the control system of lipid oxidation in the membrane was carried out. This control system involves a relationship between AOA changes, lipid composition, their oxidative ability and the nuclear membrane structure. It was shown that after irradiation the control system in the nuclei of tumor cells had the same state as before irradiation and was different from the normal one. The control system in the nuclei of tumor-host liver after irradiation starts to work in a regime which is characteristic of irradiated cells. It was shown that the principle difference in the control system functioning in tumor and tumor-host nuclei disappeared after irradiation.     

Radiation-induced morphologic changes in the rhesus monkey (Macaca mulatta) brain

The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of another project were studied histopathologically 1-30 days after a single dose of 60Co-irradiation. Histopathologically, inflammation and gliosis consistently occurred at specific time points but varied in severity between individuals. Multifocal hemorrhage, edema, and an acute neutrophilic inflammatory response were observed initially whereas perivascular accumulations of lymphocytes were observed in specimens at the end of the study. Microglia/macrophages were most prominent during the first week after irradiation, whereas astrocytes were reactive throughout the observation period. The early clinical manifestations of the central nervous system (CNS), because of brain irradiation in humans, correspond temporally with acute vascular responses, acute and subacute inflammatory cell responses, and subacute demyelination and reactive astrocytic and microglial responses observed in the rhesus monkey. Initial responses of the CNS to gamma-irradiation may have potential implications for the development of radiation-induced late injury of the CNS.     

The effect of autoblood in a hyposmotic state on the colony-forming activity of hematopoietic stem cells]

It has been shown that hypoosmotic autoblood injected sub- or intracutaneously stimulates the colony-forming activity of haemopoietic stem cells in mice. Autoblood injected to animals immediately after their irradiation stimulates haemopoiesis even after a single dose. When mice are injected with autoblood prior to irradiation, the time between the first injection and the day of irradiation is critical for manifestation of the immunomodulating effect. Autoblood infusions immediately before, the day before, or two days before irradiation markedly deteriorate the clinical status of experimental animals and cause death in some of them. It is suggested that stimulation of haemopoiesis is associated with the appearance in the blood stream of a population of radiosensitive cells, apparently T-cell precursors.     

The functional activity of the central nervous system in the early postradiation periods after exposure to gamma quanta at different doses]

Behavioral reactions of rats at early postradiation period have been studied after irradiation in sublethal and lethal dose range. Changes in functional activity of the central nervous system develop in correlation with the stages of X-ray damage.