scholarly journals Elastase-like enzymes in human neutrophils localized by ultrastructural cytochemistry.

1980 ◽  
Vol 84 (1) ◽  
pp. 102-119 ◽  
Author(s):  
J M Clark ◽  
D W Vaughan ◽  
B M Aiken ◽  
H M Kagan
Keyword(s):  
Bone Marrow ◽  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Nuclear Membrane ◽  
Active Site ◽  
Blood Cells ◽  
Human Neutrophils ◽  
Alkaline Ph ◽  
Ph Optimum ◽  
Ultrastructural Studies

The thiol ester N-t-Boc-L-alanine-p-nitrothiophenyl ester (Boc-Ala-SNp) was synthesized and applied as an ultrastructural cytochemical substrate for intracellular elastase-like enzymes. Mature human neutrophils incubated with Boc-Ala-SNp and gold ions generate an electron-dense reaction product, gold p-nitrothiophenolate, which is found in the nuclear membrane, Golgi complex, endoplasmic reticulum, mitochondria, and granules of these cells. Enzyme activity against Boc-Ala-SNp is also observed in developing monkey bone marrow neutrophils and in other blood cells. The intracellular neutrophil enzyme activity is elastase-like because it is characterized by a slightly alkaline pH optimum and is inactivated by exposure of the cells to general and specific active site inhibitors of neutrophil elastase. This substrate appears to have important potential for use in ultrastructural studies of intracellular elastase-like enzymes.

PHOSPHODIESTERASE AND ACID PHOSPHATASE ACTIVITIES OF AVIAN BONE MARROW CELLS

1965 ◽  
Vol 43 (8) ◽  
pp. 1319-1328 ◽  
Author(s):  
Gerald Kingsley Bristow ◽  
Esther W. Yamada
Keyword(s):  
Bone Marrow ◽  
Acid Phosphatase ◽  
Bone Marrow Cells ◽  
Intracellular Distribution ◽  
Specific Substrate ◽  
Magnesium Ions ◽  
Differential Centrifugation ◽  
Alkaline Ph ◽  
Ph Optimum ◽  
Rna And Dna

Avian bone marrow has been found to contain a phosphodiesterase as well as an acid phosphatase. Some properties of these enzymes have been described. Because the phosphodiesterase of this tissue has an alkaline pH optimum, is activated by magnesium ions, and acts on the specific substrate p-nitrophenyl thymidine 5′-phosphate, it is probably a phosphodiesterase I such as is present in snake venom and other tissues.The intracellular distribution of these two enzymes in normal and regenerating bone marrow was studied. Subcellular fractions were prepared by differential centrifugation or by centrifugation through sucrose density gradients. The RNA and DNA content of each fraction was determined. By the methods used no differences in the properties or intracellular distribution of the two enzymes in normal and regenerating bone marrow were found.

scholarly journals Ultrastructural localization of elastase-like enzymes in human neutrophils.

1980 ◽  
Vol 28 (1) ◽  
pp. 90-92 ◽  
Author(s):  
J M Clark ◽  
B M Aiken ◽  
D W Vaughan ◽  
H M Kagan
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Complex ◽  
Nuclear Membrane ◽  
Neutrophil Elastase ◽  
Ultrastructural Localization ◽  
Human Neutrophils ◽  
Specific Chemical ◽  
Thiol Ester ◽  
Significant Potential ◽  
Dense Deposits

The thiol ester, N-t-butyloxycarbonyl-L-alanine-p-nitrothiophenyl ester (Boc-Ala-SNp) has been synthesized and applied as an ultrastructural cytochemical substrate for leukocytic elastase-like enzymes. Incubation of fixed human neutrophils with Boc-Ala-SNp in the presence of gold ions generates electron-dense deposits of gold p-nitrothiophenolate in the nuclear membrane, endoplasmic reticulum, Golgi complex, mitochondria, and granules. Deposition of product is inhibited by pretreatment of cells with general and specific chemical inactivators of neutrophil elastase. This substrate appears to have significant potential as a probe for the ultrastructural localization of elastase-like activity.

scholarly journals APPEARANCE AND DISTRIBUTION OF FERRITIN IN MOUSE PERITONEAL MACROPHAGES IN VITRO AFTER UPTAKE OF HETEROLOGOUS ERYTHROCYTES

1973 ◽  
Vol 57 (2) ◽  
pp. 289-305 ◽  
Author(s):  
Martha E. Fedorko ◽  
Nicholas L. Cross ◽  
James G. Hirsch
Keyword(s):  
Endoplasmic Reticulum ◽  
Light Microscopy ◽  
Blood Cells ◽  
Peritoneal Macrophages ◽  
Red Cell ◽  
Cytoplasmic Matrix ◽  
Cytoplasmic Granules ◽  
Ultrastructural Studies ◽  
Mouse Peritoneal Macrophages

Mouse peritoneal macrophages have been studied in vitro after ingestion of treated rat, rabbit, or sheep erythrocytes. Under light microscopy, phagocytic vacuoles persist up to 24 h. Macrophages lose benzidine reactivity about 5 h after red cell ingestion, and they become prussian blue positive at 2 days. Ultrastructural studies show little or no ferritin in control macrophages not fed erythrocytes. In contrast, after red cell ingestion, ferritin is widely distributed in the cytoplasmic matrix and in some cytoplasmic granules by 48 h. The Golgi complex, pinocytic vacuoles, endoplasmic reticulum, nuclei, and mitochondria do not contain ferritin. Between 2 and 4 days, ferritin in cytoplasmic granules increases, concomitant with decrease in the ferritin in the cytoplasmic matrix. Evidence is presented suggesting that ferritin in the cytoplasmic matrix is translocated into cytoplasmic granules by autophagy. Polyacrylamide gel studies on macrophages after uptake of red blood cells labeled with radioiron confirm that macrophages produce radiolabeled ferritin by 4 days.

Glycogen in guinea pig neutrophils: Ultrastructural study of neutrophils at the intradermal site of BCG injection

1983 ◽  
Vol 41 ◽  
pp. 726-727
Author(s):  
Corazon D. Bucana
Keyword(s):  
Bone Marrow ◽  
Guinea Pig ◽  
Electron Density ◽  
Peritoneal Cavity ◽  
Ultrastructural Study ◽  
Guinea Pigs ◽  
Random Distribution ◽  
Glycogen Content ◽  
Polymorphonuclear Neutrophils ◽  
Ultrastructural Studies

In the circulating blood of man and guinea pigs, glycogen occurs primarily in polymorphonuclear neutrophils and platelets. The amount of glycogen in neutrophils increases with time after the cells leave the bone marrow, and the distribution of glycogen in neutrophils changes from an apparently random distribution to large clumps when these cells move out of the circulation to the site of inflammation in the peritoneal cavity. The objective of this study was to further investigate changes in glycogen content and distribution in neutrophils. I chose an intradermal site because it allows study of neutrophils at various stages of extravasation.Initially, osmium ferrocyanide and osmium ferricyanide were used to fix glycogen in the neutrophils for ultrastructural studies. My findings confirmed previous reports that showed that glycogen is well preserved by both these fixatives and that osmium ferricyanide protects glycogen from solubilization by uranyl acetate.I found that osmium ferrocyanide similarly protected glycogen. My studies showed, however, that the electron density of mitochondria and other cytoplasmic organelles was lower in samples fixed with osmium ferrocyanide than in samples fixed with osmium ferricyanide.

Morphological and biochemical analyses of changes in rat hepatocytes related to wine and ethanol consumption

1984 ◽  
Vol 42 ◽  
pp. 232-233
Author(s):  
S.M. Geyer ◽  
C.L. Mendenhall ◽  
J.T. Hung ◽  
E.L. Cardell ◽  
R.L. Drake ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Endoplasmic Reticulum ◽  
Enzyme Activity ◽  
Malic Enzyme ◽  
Smooth Endoplasmic Reticulum ◽  
Rat Hepatocytes ◽  
Mature Male ◽  
Treatment Groups ◽  
Malic Enzyme Activity ◽  
Biochemical Analyses

Thirty-three mature male Holtzman rats were randomly placed in 3 treatment groups: Controls (C); Ethanolics (E); and Wine drinkers (W). The animals were fed synthetic diets (Lieber type) with ethanol or wine substituted isocalorically for carbohydrates in the diet of E and W groups, respectively. W received a volume of wine which provided the same gram quantity of alcohol consumed by E. The animals were sacrificed by decapitation after 6 weeks and the livers processed for quantitative triglycerides (T3), proteins, malic enzyme activity (MEA), light microscopy (LM) and electron microscopy (EM). Morphometric analysis of randomly selected LM and EM micrographs was performed to determine organellar changes in centrilobular (CV) and periportal (PV) regions of the liver. This analysis (Table 1) showed that hepatocytes from E were larger than those in C and W groups. Smooth endoplasmic reticulum decreased in E and increased in W compared to C values.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

scholarly journals Inhibition studies of alkaline phosphatase in hard tissue-forming cells.

1975 ◽  
Vol 23 (5) ◽  
pp. 342-347 ◽  
Author(s):  
A Linde ◽  
B C Magnusson
Keyword(s):  
Alkaline Phosphatase ◽  
Enzyme Activity ◽  
Adenosine Triphosphatase ◽  
Ruthenium Red ◽  
Inorganic Pyrophosphatase ◽  
Alkaline Ph ◽  
Hard Tissue ◽  
Assay Condition ◽  
Phosphatase Inhibitors ◽  
Inhibition Studies

The effects of the alkaline phosphatase inhibitors levamisole and R 8231 on p-nitro-phenylphosphatase, inorganic pyrophosphatase and adenosine triphosphatase (ATPase) activities in dentingenically active odontoblasts were studied. The p-nitrophenylphosphatase and inorganic pyrophosphatase activities were inhibited, while 40% of the ATP-splitting enzyme activity remained under the assay condition used. This finding, togeather with earlier studies, indicates that at least two different phosphatase are active at alkaline pH in hard tissue-forming cells; on nonspecific alkaline phosphatase and one specific ATPase. The ATPase activity is uninfluenced by ouabain and ruthenium red and is activated by Ca-2+ ions.

Transplantation of Bone Marrow as Compared with Peripheral-Blood Cells from HLA-Identical Relatives in Patients with Hematologic Cancers

2001 ◽  
Vol 344 (3) ◽  
pp. 175-181 ◽  
Author(s):  
William I. Bensinger ◽  
Paul J. Martin ◽  
Barry Storer ◽  
Reginald Clift ◽  
Steven J. Forman ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Blood Cells ◽  
Peripheral Blood Cells
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