Asebotoxin-induced centrogenic pulmonary hemorrhage in guinea pigs.
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Biomedical subjects
Publications and source records attributed to Y Hotta.
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Characteristics features of the histopathological findings of the ossification of the posterior longitudinal ligament (OPLL) of the cervical spine are as follows: 1. In the segmental type of OPLL, the ossification of fibers usually initiates near the posterior border of the vertebral body and in those fibers which attach to the edge of the vertebral body. 2. At the axial ossifying point, degeneration of fibers occurs and enchondral ossification process follows, while in other part of the ossifying area, different types of ossification processes may also occur. 3. In association with OPLL, especially in the hyperostotic type, other paraspinal soft tissues may exhibit proliferation of the cartilage cells with or without ossification, implying the presence of ossifying tendency of the whole body. Of these tissues, the periosteum, the annulus fibrosus and/or the dura mater demonstrate proliferating changes in direct contact with OPLL, and the involvement of the periosteum precedes the other changes including OPLL, suggesting some influence from the vertebral side over the ossifying process of the paraspinal soft tissues.
Although it is known that caerulein exerts an action on the secretory activity of the islets of Langerhans in the pancreas, the mechanism of this hormone has not yet been ascertained. The present investigation was undertaken to observe the ultramicroscopic changes of the pancreatic islets and the peripheral blood levels of insulin, glucagon, glucose and electrolites after caerulein administration. The animals were divided into four groups, and three were injected intraperitoneally with caerulein at 25 micrograms/kg, 2 micrograms/kg and 0.2 microgram/kg body weight, respectively. The fourth group served as the control. In the first group (25 micrograms caerulein), the endocrine cells of the pancreatic islets showed accelerated functioning immediately and up to about 2 hours after injection. Then these cells degenerated due to cytoplasmic edema and evidenced decreased secretory activity. In the second group (2 micrograms) depression in the secretory activity occurred for about 2 hours immediately after the injection, but there was no destruction of cells and they gradually recovered their functioning. The third group (0.2 microgram) displayed an acceleration of secretory activity immediately after the injection and then recovered to the normal state. There were some changes of electrolites in the peripheral blood in each of the three groups, suggesting that caerulein causes acceleration and depression of the secretory activities in the islets of Langerhans in the pancreas depending on the dosage. Moreover, the cell alterations may well depend on the changes of electrolites in the inner and outer atmospheres of the cells.
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Relationship between chemical structure, positive inotropic potency and lethal dose of grayanotoxins and the related compounds was studied using guinea pigs. The positive inotropic effect (PIE) was examined in their papillary muscle isolated from the heart. The potency of these compounds was expressed by pD2 values, and was determined by depicting the concentration-PIE curve for each compound. The study has clarified the contribution of functional groups in the molecule; the presence of 3 beta-hydroxyl, 6 beta-hydroxyl and 10 beta-methyl groups attached to the grayanane skeleton is established to be essential for the development of PIE. The inotropic potency of compounds carrying these essential groups is increased by a 10 alpha-hydroxyl group and the acylation of the 14 beta-hydroxyl group. LD50 value of 10 compounds with a high cardiotonic potency (pD2 greater than 4) was determined by up and down method using male guinea pigs. The relation of LD50 to pD2 bore a significant correlation (r = 0.68, p less than 0.05). The most cardiotropic and toxic compound found in this study was asebotoxin III.
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Properties of the helix-destabilizing protein from Lilium meiotic cells, 'R-protein', have been examined after treating it either with alkaline phosphatase or with two types of protein kinase. Dephosphorylation with the phosphatase increases binding capacity for single-strand DNA, but abolishes specificity of binding. Dephosphorylated R-protein binds equally to single and double-strand DNA. The capacity to facilitate denaturation or renaturation of DNA is also abolished by the treatment, but cooperativity characteristics are unaffected. The consequences of protein kinase treatment of native or dephosphorylated R-protein depend upon the origin of the kinase. Heterologous cyclic-AMP-dependent protein kinase cannot reverse the effects of dephosphorylation. However, it abolishes the binding affinity of either native or dephosphorylated R-protein for DNA. A protein kinase isolated from meiotic cells has no effect on the native protein, but it does restore all native properties tested to the dephosphorylated form after phosphorylating approximately two residues/molecule of protein.
DNA metabolism was analyzed in spermatocytes of mice that were sterile either because of X-autosome or autosome-autosome translocations, or because of trisomy. In the strains analyzed, spermatogenic development is arrested by metaphase I or soon thereafter. In all such strains a disruption of the normal pattern of pachytene DNA metabolism occurred. Prepachytene metabolism appeared normal. Disruption was manifest in both the level of endogenously generated nicks during pachytene and in the distribution of nicks among the different DNA sequence classes. Nicking was more intense in the steriles and tended to be randomized in distribution. Satellite DNA underwent pachytene nick-repair in the steriles but not in fertile controls. The repair capacity of spermatocytes from steriles was equal to that of the fertiles; the higher frequency of nicks in the steriles was due to a persistence of nicking activity.
The sex appeal of a Drosophila melanogaster female is defined here as the stimulus (or set of stimuli) which induces wing vibration in courting males. A quantitative measure of sex appeal is the cumulative duration of wing vibration induced by a given female averaged over several consecutive test intervals using different standardized male testers (sex appeal parameter, SAP). By use of SAP, both males and females are found to have the same amount of sex appeal on the first day after eclosion. However, males rapidly lose it by the next day, so that mature males become distinct from females. We report the ontogeny of the male's response to sex appeal. By the SAP method, we also demonstrate that the male's response is dependent on his previous encounter with females. The sex appeal of 287 gynandromorphs was examined in order to localize the sex appeal focus by means of blastoderm fate mapping. Most mosaic flies were classified as either positive (femalelike, with high SAPs) or negative (malelike, with SAPs of zero). Sixteen percent of the gynandromorphs had intermediate levels of SAP, inducing only short vibrations, a response which males rarely give to normal females. Assuming that the gynanders with such intermediate sex appeal must have both female and male foci, distances to the foci from external landmarks were calculated. The center of the focus seems to be an internal structure mapping to the ventroposterior region of the blastoderm fate map, close to the primordia of the anterior sternites. The focus might include a large mesodermal area, but only part of it must have a female genotype for the sex appeal to be expressed. A possible involvement of the fat bodies in production of the sex appeal stimulus is discussed in relation to these findings. Consistent with this conclusion is the fact that females whose abdomens were amputated still retain enough sex appeal to induce male wing vibrations.
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Potentiating effects of GSH, a physiologic kininase inhibitor on the bradykinin actions on (a) blood pressure responses of rabbits, (b) acute inflammatory response in rat's hind paws and (c) the isolated guinea-pig ileum contractions were examined among the combinations between various active agents and thiols. The potentiation of the hypotensive response to bradykinin by GSH was highly specific compared with the other experimental models (B and C). Throughout these three experiments, specific relation between GSH and bradykinin was consistently observed.
Mouse spermatocytes were labelled in situ with 3H-thymidine at successive stages of meiosis. Isolated mouse as well as human spermatocytes were similarly labelled under in vitro conditions. DNA synthesis was followed either by tracking radioactivities in Cs2SO4 gradients or by measuring reassociation kinetics. Mouse satellite DNA and the 3 satellites of human DNA are labelled during S-phase but not during pachytene. In the mouse genome, there is a preferential labelling of regions containing foldbacks (human spermatocytes were not analyzed in this respect). The absence of detectable pachytene synthesis in satellite DNA is consistent with genetic evidence on the absence of crossing-over in constitutive heterochromatin.
An ATP-dependent DNA unwinding protein is present at a high level of activity in meiotic cells of lilies. The protein also acts as a DNA-dependent ATPase, the single strand form being the preferred cofactor. It binds in the absence of ATP to single-strand DNA and to ends or nicks in duplex DNA. A 3'-OH terminus is required for binding at duplex ends; such binding is highly stable. Unwinding occurs in the presence of ATP, and it is limited to about 50 base pairs per end or 400-500 base pairs per nick. The ATP hydrolyzed during unwinding is distinguishable from ATP hydrolysis in the presence of single-strand DNA.
Since animal behaviour is executed through neuronal circuits including sensory receptors and muscle, genes vital for their development and differentiation must be found among mutants having behavioural anomaly. After mutagenesis with ethyl methanesulphonate (EMS), we screened for X-linked flightless mutants of Drosophila melanogaster by using column-type flight tester. Approximately 10(4) individuals were screened and 21 mutant genes were isolated. Chromosomal mapping and complementation experiments revealed that they belong to 15 cistrons randomly located on X chromosome, three cistrons having more than two alleles. Two of the isolated mutants (fltO2 and fltH, which are recessive both behaviourally and morphologically) were analysed with the mosaic fate mapping technique, and both were found to have their primary foci in mesodermal region of blastoderm, suggesting that the genes exert their primary effect in indirect flight muscle. Electronmicroscopic studies on the muscles from four alleles of the fltO2 cistron revealed an abnormality in myofibrillar arrangement. A possible deficit within Z-band components is discussed in relation to wings-up B mutants. The indirect flight muscle of flltH was also examined, and it was found that sarcomere length and diameter of myofibrils were abnormal. It was postulated that a possible factor which controls size of myofibrils is defective in this mutant. These examples indicate the advantage of combining ultrastructural examination with genetic mosaic mapping technique.
The preventive effect of ursodesoxycholic acid on pancreatic injury by alloxan (alloxan diabetes) has been reported by Watari, et al. (1976). In the following experiment, to pursue the findings further, ursodesoxycholic acid was used curatively for alloxan diabetes. A first group of animals (5 mice) were injected with alloxan (4 mg) twice at the fifth and tenth day. The second group (5 mice) was injected with ursodesoxycholic acid (0.2 mg each) for 14 days during the experiment in addition to the same alloxan dosage/frequency as the first group. A third group of animals (5 mice) served as the control. The animals were sacrificed on the 15th day and the blood sugar levels were examined, using commercial test paper. The pancreatic tissues were fixed in a mixture of 2.5% glutaraldehyde and 2% osmid acid solution, which was adjusted at pH 7.4 with a veronal acetate buffer; the osmotic pressure was also regulated by adding sucrose of 0.045 g/ml. Following dehydration using a series of alcohol concentrations, the tissues were embedded in Epon 812. Thin sections were cut with a Porter-Blum MT-2B ultramicrotome, stained with both uranyl acetate and a lead mixture, and then observed by electron microscopy. The results were as follows: The pancreatic islet cells, especially of B-cells in the first group of animals injected with alloxan only, were seriously damaged and contained myelinated mitochondria. Golgi apparatus, and an increasing number of autophagic vacuoles. Some B-cells revealed hydropic degeneration. Some B-granules changed into vacuoles after diacrine secretion. Pancreatic A-cells were increased in number and showed no cell injuries. On the other hand, the pancreatic B-cells of mice treated with both alloxan and ursodesoxycholic acid maintained almost normal fine structures. In summary, ursodesoxycholic acid has a curative effect on alloxan-induced pancreatic B-cell injury.
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