Experimental investigations in prolonged myocardial ischaemia. Note I. Biology of the myocardial fiber after transient myocardial fiber after transient myocardial ischaemia

The first ten days' evolution of post-ischaemic lesions of the premonitory or angina pectoris syndrome type was experimentally studied by the challenge of a short-term (10 and 15 min) ischaemia, of an adaptation to ischaemia and an adaptation followed by prolonged ischaemia (20 and 35 min). Worthy of note was the persistence of reversible lesions after short-term ischaemia and adaptation, and the progressive evolution towards cytolysis and cicatrization of some pancicellular foci after adaptation followed by prolonged ischaemia. The role of mitochondrial lesions, of lysosomal hydrolases, the inefficiency of renewed circulation, as well as problems of diagnosis are discussed.     

Q fever urban cases in Romania

Q fever urban sporadic cases in Romania in the 1981-87 period are reviewed as concerns their incidence, seasonality and epidemiological data. Urban cases represented 76.8% as against 23.2% rural cases from the 134 Q fever sporadic cases detected in this period. Cases were distributed throughout all months with peaks during April (18.4% of cases) and June (19.4%). Infections were not related to contact with livestock or domestic birds or with raw milk drinking. Cases could not be identified as Q fever occupational ones. 36.7% of patients were working in nonalimentary industry and only 12.6% were involved in meat industry, veterinary or human medical practices. New studies concerning unusual sources of urban infection such as dogs, cats or urban street pigeons are emphasized.     

Cell-membrane phospholipase C is involved in inducing the antiviral effect of interferon

A monospecific inhibitory antibody directed to phospholipase C (phosphoinositidase C) blocked the antiviral effect of human interferons alpha and beta when tested on human quiescent fibroblasts challenged with the vesicular stomatitis virus. This action was due to specific inhibition of polyphosphoinositide hydrolysis because (a) the F(ab)₂ fragment of the antibody molecule was also inhibitory; (b) excess antibodies directed to phospholipase A₂ and to a phosphatidylcholine-preferring phospholipase C did not have any inhibitory effect, and (c) the combination of 12-O-tetradecanoylphorbol-acetate and calcium ionophore A23187 had an interferon-like antiviral effect which was not influenced by the inhibitory anti-phospholipase C antibodies. To avoid an interferon-like effect due to induction of interferon by second messengers, Vero cells, which lack interferon biosynthesis, were also used. Liposomes containing inositol 1,4,5-triphosphate and 1-oleoyl-2-acetyl-rac-glycerol protected Vero cells against the infection with the vesicular stomatitis virus. These results taken together show that phosphoinositide-derived second messengers are involved in triggering the antiviral effect of interferons alpha and beta.     

Eine Theorie über das Spektrum von Selbstlauten

Zusammenfassung Zweck des vorliegenden Aufsatzes ist es, die Form des Spektrums von Sprechsignalen, wie z.B. von Selbstlauten, zu erklären.

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Summary The aim of this paper is to explain from the mathematical point of view the vowels spectrum.

     

Middle paleozoic waulsortian-type mud mounds in Southern Fergana (Southern Tien-Shan,commonwealth of independent states): The shallow-water atoll model

Summary Several Waulsortian-type mud mounds nearly 500 m thick and about 5 km long occur in the Middle Paleozoic carbonate section of the Aktur nappe in the mountains on the right bank of Isfara river. These buildups form a well developed barrier system that stretches along the South Ferganian carbonate platform margin and divides the carbonate complex into a fore-reef and a back-reef part. The time of the mounds' most active growth was from the Late Silurian (Ludlow) to the Middle Devonian (Eifel). Three main facies types can be recognized in the mud mounds: 1. micritic core facies, 2. sparitic flank facies and 3. loferitic capping facies. The central massive or crudely bedded part of the mounds consists of white or light grey clotted micrite. Macrofossils are rare. The sparitic flank facies in contrast consists of coarse and densely packed crinoidal wackestone-floatstones with some brachiopod shell debris. Solitary rugose corals, tabulate corals, stromato-poroids and fragments of mollusks are also abundant. The tops of the mounds are usually covered with loferitic pelmicrites or oolitic grainstone caps. Stromatactis-like structures are very rare and poorly developed in the South Ferganian mud mounds. However, almostin all such mounds horizons of calcitic breccias can be found. In order to explain all the features found in the Fergana mounds an ‘atoll-like’ model has been proposed which starts the evolution of the mud mounds with a small nucleus bioherm. The main stage of the evolution corresponds to an atoll-like structure developing on the surface of shallow water platforms. White clotted micrite of the mound core facies is interpreted as a accumulation of fine-grained sediment in an inner lagoon flanked by crinoidal bar deposits. The mound flank facies represents the atoll rim deposits from where the carbonate mud is derived. The capping loferitic facies is considered as tidal flat deposit that developed on top of the buildups during the last stage of its evolution. The knoll shape of the mounds is explained by the retreat of the atoll flanking crinoidal bars back into the inner lagoon during the rise in sea level. Stromatactis-like structures of small cavities filled with sparry calcite owe their existence to burrowing organisms. Calcitic breccias are interpreted as paleokarst collapse breccias. They indicate that the tops of the mud mound became subaerially exposed. Other evidence for a subaerial exposure can be seen in the occurrence of Variscian ‘black and white’ limestone gravel on the tops of some mud mounds. According toWard et al. (1970) these sediments were produced above the sea level at the edge of hypersaline lakes situated on islands.     

Organization of centromeres in the decondensed nuclei of mature human sperm

The localization of centromeres in mature human sperm was shown by immunofluorescent labeling and nonisotopic in situ hybridization. In the decondensed nucleus structural elements (dimers, tetramers, linear arrays and V shape structures) formed by individual centromeres of nonhomologous chromosomes were observed. They organize the compact chromocenter, which was shown for nuclei decondensed to a low extent. The chromocenter is buried inside the nucleus; in contrast, telomeric regions of chromosomes were tentatively localized on the periphery. Thus, a gross architecture, which can influence selective unpackaging of the paternal genome upon fertilization, exists in human sperm.     

The role of ecosystem transpiration in creating alternate moisture regimes by influencing atmospheric moisture convergence

The terrestrial water cycle links the soil and atmosphere moisture reservoirs through four fluxes: precipitation, evaporation, runoff, and atmospheric moisture convergence (net import of water vapor to balance runoff). Each of these processes is essential for sustaining human and ecosystem well-being. Predicting how the water cycle responds to changes in vegetation cover remains a challenge. Recently, changes in plant transpiration across the Amazon basin were shown to be associated disproportionately with changes in rainfall, suggesting that even small declines in transpiration (e.g., from deforestation) would lead to much larger declines in rainfall. Here, constraining these findings by the law of mass conservation, we show that in a sufficiently wet atmosphere, forest transpiration can control atmospheric moisture convergence such that increased transpiration enhances atmospheric moisture import and results in water yield. Conversely, in a sufficiently dry atmosphere increased transpiration reduces atmospheric moisture convergence and water yield. This previously unrecognized dichotomy can explain the otherwise mixed observations of how water yield responds to re-greening, as we illustrate with examples from China's Loess Plateau. Our analysis indicates that any additional precipitation recycling due to additional vegetation increases precipitation but decreases local water yield and steady-state runoff. Therefore, in the drier regions/periods and early stages of ecological restoration, the role of vegetation can be confined to precipitation recycling, while once a wetter stage is achieved, additional vegetation enhances atmospheric moisture convergence and water yield. Recent analyses indicate that the latter regime dominates the global response of the terrestrial water cycle to re-greening. Evaluating the transition between regimes, and recognizing the potential of vegetation for enhancing moisture convergence, are crucial for characterizing the consequences of deforestation as well as for motivating and guiding ecological restoration.     

Soluble Sema4D cleaved from osteoclast precursors by TACE suppresses osteoblastogenesis

Bone remodelling is mediated by orchestrated communication between osteoclasts and osteoblasts which, in part, is regulated by coupling and anti-coupling factors. Amongst formally known anti-coupling factors, Semaphorin 4D (Sema4D), produced by osteoclasts, plays a key role in downmodulating osteoblastogenesis. Sema4D is produced in both membrane-bound and soluble forms; however, the mechanism responsible for producing sSema4D from osteoclasts is unknown. Sema4D, TACE and MT1-MMP are all expressed on the surface of RANKL-primed osteoclast precursors. However, only Sema4D and TACE were colocalized, not Sema4D and MT1-MMP. When TACE and MT1-MMP were either chemically inhibited or suppressed by siRNA, TACE was found to be more engaged in shedding Sema4D. Anti-TACE-mAb inhibited sSema4D release from osteoclast precursors by ~90%. Supernatant collected from osteoclast precursors (OC-sup) suppressed osteoblastogenesis from MC3T3-E1 cells, as measured by alkaline phosphatase activity, but OC-sup harvested from the osteoclast precursors treated with anti-TACE-mAb restored osteoblastogenesis activity in a manner that compensates for diminished sSema4D. Finally, systemic administration of anti-TACE-mAb downregulated the generation of sSema4D in the mouse model of critical-sized bone defect, whereas local injection of recombinant sSema4D to anti-TACE-mAb-treated defect upregulated local osteoblastogenesis. Therefore, a novel pathway is proposed whereby TACE-mediated shedding of Sema4D expressed on the osteoclast precursors generates functionally active sSema4D to suppress osteoblastogenesis.     

Design and preclinical testing of an anti-CD41 CAR T cell for the treatment of acute megakaryoblastic leukaemia

Acute megakaryoblastic leukaemia (AMkL) is a rare subtype of acute myeloid leukaemia (AML) representing 5% of all reported cases, and frequently diagnosed in children with Down syndrome. Patients diagnosed with AMkL have low overall survival and have poor outcome to treatment, thus novel therapies such as CAR T cell therapy could represent an alternative in treating AMkL. We investigated the effect of a new CAR T cell which targets CD41, a specific surface antigen for M7-AMkL, against an in vitro model for AMkL, DAMI Luc2 cell line. The performed flow cytometry evaluation highlighted a percentage of 93.8% CAR T cells eGFP-positive and a limited acute effect on lowering the target cell population. However, the interaction between effector and target (E:T) cells, at a low ratio, lowered the cell membrane integrity, and reduced the M7-AMkL cell population after 24 h of co-culture, while the cytotoxic effect was not significant in groups with higher E:T ratio. Our findings suggest that the anti-CD41 CAR T cells are efficient for a limited time spawn and the cytotoxic effect is visible in all experimental groups with low E:T ratio.