scholarly journals FURTHER STUDIES ON PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN

1960 ◽  
Vol 112 (4) ◽  
pp. 619-634 ◽  
Author(s):  
Henry H. Freedman
Keyword(s):  
Direct Action ◽  
White Blood Cells ◽  
Test Dose ◽  
Blood Stream ◽  
Passive Transfer ◽  
Bacterial Endotoxin ◽  
Second Phase ◽  
Normal Numbers ◽  
Febrile Response ◽  
Long Term Treatment

The effect of various schedules for inducing tolerance to bacterial endotoxin in donor rabbits upon suitability for demonstration of passive transfer of tolerance to pyrogenicity in normal recipients has been investigated. Long-term treatment of donors, through 5 weeks, is no more effective than a brief series of injections, adding further evidence that tolerance is not attributable to specific antibody to the endotoxin. Qualitative differentiation of the febrile pattern of passively tolerant recipients from that seen in control animals depends upon the magnitude of the test dose of pyrogen. Passively tolerant rabbits respond to endotoxin with an acute leucopenia equivalent to that seen in controls suffering a full biphasic fever. Animals given daily injections of endotoxin continue to show the acute leucopenia, despite the early modification of the course of fever characteristic of endotoxin tolerance. The assumption that the leucopenia reflects damage to the leucocytes, with release of endogenous pyrogen, is not consistent with these findings. Rabbits rendered leucopenic by nitrogen mustard and then given endotoxin exhibit a rapidly developing fever of greater than normal intensity, the exaggeration of the febrile response being proportional to the severity of the induced leucopenia. The implications of these findings for the pathogenesis of endotoxin-induced fever are discussed. The evidence supports the hypothesis that endotoxin produces fever by direct action rather than by release of endogenous leucocytic pyrogen. It is postulated that the lesser fever, in animals having normal numbers of circulating leucocytes, reflects a limitation of available endotoxin by the known rapid sequestration in the white blood cells at the time of the acute leucopenia. It is further suggested that the biphasic febrile response of the normal rabbit results from reinoculation of the blood stream by the temporarily sequestered endotoxin, the RES of the tolerant animal clearing the released endotoxin at a rate sufficient to prevent triggering the second phase of fever.

scholarly journals PASSIVE TRANSFER OF TOLERANCE TO PYROGENICITY OF BACTERIAL ENDOTOXIN

1960 ◽  
Vol 111 (4) ◽  
pp. 453-463 ◽  
Author(s):  
Henry H. Freedman
Keyword(s):  
Endotoxin Tolerance ◽  
Passive Transfer ◽  
Bacterial Endotoxin ◽  
Febrile Response ◽  
Highly Sensitive ◽  
Altered Response ◽  
Prior Administration

The typical febrile response of normal rabbits given bacterial endotoxin intravenously may be modified by prior administration of plasma or, less effectively, serum of endotoxin-tolerant donors. This altered response is characterized by disappearance of the second rise in fever and by a striking reduction in fever index. It thus resembles the course of fever shown by rabbits made tolerant to endotoxin by one or more previous daily doses. This transfer of tolerance by plasma or serum depends critically upon the manner in which tolerance is induced in the donors. The plasma of donor rabbits made tolerant, then given an RES-blocking dose of carbon, still confers tolerance upon normal recipient rabbits. Such donors have lost their tolerance and are highly sensitive to endotoxin at the time their blood is taken. The implications of these findings for endotoxin tolerance and for transfer of this phenomenon are discussed. The evidence is consistent with the hypothesis that both tolerance and its transfer are based upon RES function and are independent of antibody.

Abstract 023: Collecting Duct (Pro)Renin Receptor Mediates Angiotensin II-induced Hypertension

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Fei Wang ◽  
Kexin Peng ◽  
Xiaohan Lu ◽  
Kevin Yang ◽  
Mi Liu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Direct Action ◽  
Collecting Duct ◽  
Second Phase ◽  
Na Transport ◽  
Dual Effect ◽  
Induced Hypertension ◽  
Nanomolar Range ◽  
Local Generation ◽  
Specific Deletion

Within the kidney, (pro)renin receptor (PRR) is predominantly expressed in the intercalated cells (IC) of collecting duct (CD) where its expression is induced by angiotensin II (AngII). Here we examined the function of PRR in the CD by analyzing mice with CD-specific deletion of PRR (CD PRR KO) using AQP2-Cre which has recently been shown to target both IC and principal cells (PC). Radiotelemetry demonstrated that the null mice were largely resistant to AngII-induced hypertension (MAP on day 7: Floxed/AngII 137.4 ± 3.5 vs. KO/AngII 121.2 ± 1.1 mmHg, p<0.05, n=4), accompanied with reduced urinary soluble PRR (sPRR) and aldosterone levels. Electrophysiology analysis demonstrated that within minutes activation of PRR by 10 nM prorenin induced a transient increase in amiloride-sensitive Na+ transport in cultured mpkCCD cells (Ieq: 1.85 ± 0.17 vs. 1.30 ± 0.06 μA/cm2, p<0.05). Interestingly, this was followed by a second phase of ENaC activation after 6 h, which reached the plateau activation at 24 h, accompanied with increased aldosterone release as assessed by ELISA (14.41 ± 0.92 vs. 5.45 ± 0.28 pg/ ml/μg protein, p<0.05). The chronic but not acute phase of ENaC activation was abolished by eplerenone. Both phases of ENaC activation depended on Nox4-derived reactive oxygen species (ROS). Immunostaining using an antibody against sPRR (the N terminus) showed exclusive labeling in the principle cells (PC) whereas the labeling with the C-terminal antibody was exclusively found in IC. A recombinant histidine-tagged sPRR, termed sPRR-His, in the nanomolar range induced a similar dual effect on ENaC activation as prorenin. Intravenous infusion of sPRR-His in CD PRR KO mice for 5 days completely restored the hypertensive response to AngII (MAP: 135.5 ± 7.5 vs. 116.7 ± 5.7 mmHg, p<0.05). We conclude that: 1) CD PRR mediates AngII-induced hypertension; 2) PRR activation in the CD leads to increased ENaC activity acutely through the direct action of ROS and chronically through local generation of aldosterone; 3) sPRR derived from IC may act in a paracrine fashion to stimulate Na+ transport in PC.

scholarly journals Adult Mice With Targeted Mutation of the Interleukin-11 Receptor (IL11Ra) Display Normal Hematopoiesis

Blood ◽  
1997 ◽  
Vol 90 (6) ◽  
pp. 2148-2159 ◽  
Author(s):  
Harshal H. Nandurkar ◽  
Lorraine Robb ◽  
David Tarlinton ◽  
Louise Barnett ◽  
Frank Köntgen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Bone Marrow Cells ◽  
White Blood Cells ◽  
Null Mutation ◽  
Wild Type ◽  
Normal Numbers ◽  
Interleukin 11 ◽  
Marrow Cells

Abstract Interleukin-11 (IL-11) is a pleiotropic growth factor with a prominent effect on megakaryopoiesis and thrombopoiesis. The receptor for IL-11 is a heterodimer of the signal transduction unit gp130 and a specific receptor component, the α-chain (IL-11Rα). Two genes potentially encode the IL-11Rα: the IL11Ra and IL11Ra2 genes. The IL11Ra gene is widely expressed in hematopoietic and other organs, whereas the IL11Ra2 gene is restricted to only some strains of mice and its expression is confined to testis, lymph node, and thymus. To investigate the essential actions mediated by the IL-11Rα, we have generated mice with a null mutation of IL11Ra (IL11Ra−/−) by gene targeting. Analysis of IL11Ra expression by Northern blot and reverse transcriptase-polymerase chain reaction, as well as the absence of response of IL11Ra−/− bone marrow cells to IL-11 in hematopoietic assays, further confirmed the null mutation. Compensatory expression of the IL11Ra2 in bone marrow cells was not detected. IL11Ra−/− mice were healthy with normal numbers of peripheral blood white blood cells, hematocrit, and platelets. Bone marrow and spleen contained normal numbers of cells of all hematopoietic lineages, including megakaryocytes. Clonal cultures did not identify any perturbation of granulocyte-macrophage (GM), erythroid, or megakaryocyte progenitors. The number of day-12 colony-forming unit-spleen progenitors were similar in wild-type and IL11Ra−/− mice. The kinetics of recovery of peripheral blood white blood cells, platelets, and bone marrow GM progenitors after treatment with 5-flurouracil were the same in IL11Ra−/− and wild-type mice. Acute hemolytic stress was induced by phenylhydrazine and resulted in a 50% decrease in hematocrit. The recovery of hematocrit was comparable in IL11Ra−/− and wild-type mice. These observations indicate that IL-11 receptor signalling is dispensable for adult hematopoiesis.

scholarly journals STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

1958 ◽  
Vol 107 (3) ◽  
pp. 383-401 ◽  
Author(s):  
Elisha Atkins ◽  
Wei Cheng Huang
Keyword(s):  
Newcastle Disease ◽  
Polymorphonuclear Leukocyte ◽  
Influenza A ◽  
Passive Transfer ◽  
Endogenous Pyrogen ◽  
Febrile Response ◽  
Essential Step ◽  
Intravenous Inoculation ◽  
Intraperitoneal Inoculation

A substance with pyrogenic properties appears in the blood streams of rabbits made febrile by the intravenous inoculation of the PR8 strain of influenza A and Newcastle disease viruses (NDV). By means of a technique involving passive transfer of sera from animals given virus to recipient rabbits, the titer of circulating pyrogen was found to be closely correlated with the course of fever produced by virus. Certain properties of the pyrogen are described which differentiate it from the originally injected virus and suggest that the induced pyrogen is of endogenous origin. These properties resemble those of endogenous pyrogens occurring in other forms of experimental fever. The source of virus-induced pyrogen is unknown. In vitro incubation of virus with various constituents of the circulation did not result in the appearance of endogenous pyrogen. Granulocytopenia induced by HN2 failed to influence either fever or the production of endogenous pyrogen in rabbits injected with NDV. Similarly, the intraperitoneal inoculation of NDV into prepared exudates did not modify the febrile response. These findings do not lend support to the possibility that the polymorphonuclear leukocyte is a significant source of endogenous pyrogen in virus-induced fever. It is concluded that the liberation of an endogenous pyrogen from some as yet undefined source is an essential step in the pathogenesis of fever caused by the influenza group of viruses.

scholarly journals New Segmentation and Feature Extraction Algorithm for the Classification of White Blood Cells in Peripheral Smear Images

2021 ◽  
Author(s):  
Eslam Tavakoli ◽  
Ali Ghaffari ◽  
Seyedeh-Zahra Mousavi Kouzehkanan ◽  
Reshad Hosseini
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Dice Similarity Coefficient ◽  
Second Phase ◽  
Peripheral Smear ◽  
Color Features ◽  
Svm Model ◽  
Extraction Algorithm ◽  
Processing Techniques

This article addresses a new method for classification of white blood cells (WBCs) using image processing techniques and machine learning methods. The proposed method consists of three steps: detecting the nucleus and cytoplasm, extracting features, and classification. At first, a new algorithm is designed to segment the nucleus. For the cytoplasm to be detected, only a part of it which is located inside the convex hull of the nucleus is involved in the process. This attitude helps us overcome the difficulties of segmenting the cytoplasm. In the second phase, three shape and four novel color features are devised and extracted. Finally, by using an SVM model, the WBCs are classified. The segmentation algorithm can detect the nucleus with a dice similarity coefficient of 0.9675. The proposed method can categorize WBCs in Raabin-WBC, LISC, and BCCD datasets with accuracies of 94.47 %, 92.21 %, and 94.20 %, respectively. It is worth mentioning that the hyperparameters of the classifier are fixed only with Raabin-WBC dataset, and these parameters are not readjusted for LISC and BCCD datasets. The obtained results demonstrate that the proposed method is robust, fast, and accurate.

Separable phases of light-evoked depolarizations in the retina of Strombus

1980 ◽  
Vol 84 (1) ◽  
pp. 137-148
Author(s):  
F. N. Quandt ◽  
H. L. Gillary
Keyword(s):  
Synaptic Transmission ◽  
Voltage Clamp ◽  
Stimulus Intensity ◽  
Interstimulus Interval ◽  
Direct Action ◽  
Resting Potential ◽  
Second Phase ◽  
Reverse Polarity ◽  
Voltage Dependent ◽  
Conductance Changes

The waveforms of light-evoked depolarizations in Strombus retinal neurones can exhibit two sequential peaks or phases, the relative amplitudes of which vary with changes in stimulus intensity and interstimulus interval. Experiments employing either the passage of constant intracellular current or voltage clamp techniques indicate that both phases reverse polarity at intracellular potentials less negative than the resting potential. The potential at which the first phase reverses its polarity is considerably more positive than that of the second phase. The results indicate that the light-evoked depolarizations are generated by at least two different processes; these appear to be separate conductance changes, neither of which is voltage dependent. Under certain conditions, the second phase was inhibited by high extracellular concentrations of Mg2+, indicating that it may arise as a result of chemically mediated synaptic transmission. The first phase did not show such inhibition and appears to be caused by the direct action of light on the cell.

scholarly journals TOLERANCE TO BACTERIAL PYROGENS

1947 ◽  
Vol 86 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Paul B. Beeson ◽  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Serratia Marcescens ◽  
Passive Transfer ◽  
Characteristic Pattern ◽  
Febrile Reaction ◽  
Febrile Response ◽  
Intravenous Injections ◽  
Daily Dose ◽  
Development Of Tolerance

In a study of the febrile responses of rabbits to repeated intravenous injections of pyrogenic substances from Eberthella typhosa, Serratia marcescens, and Pseudomonas aeruginosa, the following observations were made: 1. A characteristic pattern of response to daily injections of the same dose of pyrogenic material was noted. This consisted of a progressive diminution in febrile response during the 1st week or 10 days, after which an animal responded to each injection with approximately the same degree of fever, even when the injections were continued for several weeks. 2. Animals given injections of the same amount of pyrogenic material at semiweekly or weekly intervals showed some diminution in febrile reaction but the alteration was less pronounced than that in animals injected every day. 3. Pyrogen tolerance appeared to be lost quickly. Animals allowed to rest for approximately 3 weeks reacted to readministration of pyrogen with fever comparable with that which occurred after the first injection. 4. By gradually increasing the size of the daily dose of pyrogen a tolerance could be established such that a reduced, but still considerable, amount of pyrogen caused no fever whatever. 5. Rabbits that had been injected with S. marcescens or Ps. aeruginosa pyrogens showed a diminished febrile response to E. typhosa vaccine. 6. Passive transfer of the unresponsiveness to pyrogens could not be demonstrated. 7. Prevention of temperature elevations during the course of immunization by use of an antipyretic drug did not interfere with the development of tolerance to pyrogens. 8. A series of mechanically induced bouts of fever did not reduce the responsiveness to bacterial pyrogens.

Increased Sensitivity to Endotoxin Induced Disseminated Intravascular Coagulation (DIC) in Vitamin E-Deficient Rabbits

1979 ◽  
Author(s):  
B. Lipinski ◽  
L.J. Machlin
Keyword(s):  
Blood Cells ◽  
Cell Injury ◽  
White Blood Cells ◽  
Blood Stream ◽  
Tocopheryl Acetate ◽  
Deficient Diet ◽  
Laboratory Findings ◽  
E Coli ◽  
Intravascular Coagulation ◽  
Increased Sensitivity

DIC in rabbits was induced by i.v, injection of E. coli endotoxin (e) (50μg/kg). The levels of fibrinogen (F) and FDP, fibrin monomer (FM), PTT, white blood cells and platelet counts were determined before and 3 hours after e injection. Fibrin (f) deposited in organs was calculated by counting the radioactivity of 125I-F introduced i.v, beforehand. Pretreatment of rabbits, maintained on laboratory chow, with dl-α-tocopheryl acetate (vit. E) (40mg/kg/day i.m. for 3 days) did not protect the animals against U1C induced with 2 doses of e 24 hours apart, and only slightly reduced amounts of f deposited in organs. On the other hand, rabbits maintained on a vit. E-deficient diet were found to be extremely sensitive to e. Single doses of e caused 100% mortality within 24 hours, as compared to 100% survival in a group fed the same diet containing vit. E. Laboratory findings (F depletion, presence of FM, increased FDP and prolonged PTT) and increased f deposition in organs (kidneys, lung, liver and spleen) indicated activation of intravascular coagulation by a single dose of c in vit. E-deficient rabbits. It is possible that normal levels of vit. E protect against cell injury by e and thus prevent a release of procoagulants into the blood stream.

scholarly journals ON THE RELATION OF WHITE BLOOD CELLS AND PLATELETS TO VENOM HEMOLYSIS

1956 ◽  
Vol 104 (4) ◽  
pp. 517-523 ◽  
Author(s):  
Joseph C. Turner ◽  
Keyword(s):  
Guinea Pig ◽  
Hemolytic Activity ◽  
Chromatographic Separation ◽  
Blood Cells ◽  
Direct Action ◽  
White Blood Cells ◽  
Substantial Reduction ◽  
Red Cells ◽  
Phospholipase Activity ◽  
Paper Chromatographic Separation

Removal of the white cells and platelets from suspensions of red cells usually produces substantial reduction in the hemolytic activity of venoms. Guinea pig red cells constitute a notable exception and may be lysed by a direct action of venom. White blood cells and platelets appear to contribute to hemolysis by serving as sources of phosphatides for the formation of lysophosphatides. No correlation could be found between phospholipase activity and direct hemolytic activity of venoms. A recently described method (8) of paper chromatographic separation of phospholipides has been used successfully in part of the work.

5-LIPOOXYGENASE ACTIVITY IN THE HUMAN VESSEL WALL

1987 ◽  
Author(s):  
WALL R De Caterina ◽  
D Giannessi ◽  
G Lazzerini ◽  
A Mazzone ◽  
A Azzara ◽  
...  
Keyword(s):  
White Blood Cells ◽  
Clinical Manifestations ◽  
Calcium Ionophore ◽  
Vascular Wall ◽  
Blood Stream ◽  
Selective Exposure ◽  
Mechanical Agitation ◽  
Standard Curve ◽  
Saphenous Veins ◽  
Inner Vessel

5-lipooxygenase products have been identified from a variety of cells and may play a role in the progression of atherosclerosis and in its clinical manifestations (spasm, thrombosis). We investigated whether human vascular fragments, freshly obtained at surgery, are able to produce leukotriene (LT) B4, a definite end product of 5-lipooxygenase, provided with biological activity. Fragments obtained from human saphenous veins (n=21) or aorta (fibrous plaques, n=15, atheromas, n=16) were incubated in buffer at 37°C with mechanical agitation sequentially in the absence (15 min) and in the presence (15 min) of 10 jjM calcium ionophore A-23187. At the end of each incubation, the buffer was sampled to be assayed by a specific radioimmunassay (RIA) for LTB4 (sensitivity 4.3+0.9 pg). Validation of the assay was performed by comparison with a chemotactic bioassay in Boyden chambers, by interpolation of a standard curve evaluating the chemotactic response of neutrophils to a standard LTB4 preparation. RIA resulted the only practicable method to detect concentrations lower than 2.5 ng/ml, compared both to bioassay and to HPLC, all three performed in the incubation media from 8 vascular fragments. Incubations were also performed in a chamber with selective exposure of the endothelial surface in order to detect possible production of LTB4 on the luminal site of the vessel. Both unstimulated and ionophore-stimulated LTB4 were higher (P< 0.01) in atheromas (2.7±1.2 and 6.3±1.8) than in fibrous plaques (0.51±0.22 and 1.19±0.38) or saphenous veins (0.74±0.34 and 3.07±1.39) (ng/g wet weight, mean±SD). Detectable spontaneous and stimulated LTB4 productions were also found in the incubation media of the chamber with atheromas (40±14 and 324±85 pg/cm2 area, respectively). Histology of the fragments confirmed a higher cellularity (macrophages, atherocytes) in atheromas as compared to fibrous plaques and veins. The human vascular wall is a definite site of 5-lipooxygenase activity, possibly arising from white cell infiltration. LTB4 production, able to reach the inner vessel surface and the blood stream, is a possible factor in the progression of the lesion by increasing vascular permeability or recruiting white blood cells.

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