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Biomedical subjects

L Kass

Publications and source records attributed to L Kass.

At least 91 records · Page 5Linked to original sources

Arginine methyltransferase activity in chronic erythremic myelosis (Diguglielmo syndrome).

Activity of S-adenosylmethionine-dependent arginine methyltransferase was substantially higher in sonicated bone marrow samples from 6 patients with chronic erythremic myelosis than in bone marrow from 3 patients with untreated pernicious anemia, 2 patients with autoimmune hemolytic anemia, and 4 normal persons. Increased activity of this enzyme may be one of the factors contributing to the pathogenesis fo methylated arginines in histones of erythroblasts from patients with chronic erythremic myelosis.

Arginine↗

Merging of modalities in the optic tectum: infrared and visual integration in rattlesnakes.

The optic tectum of pit vipers (Crotalinae) contains a layer of infrared-sensitive neurons subjacent to the visual layer; these indirectly receive input from the facial pit organs. They respond transiently to the appearance or motion of warm objects within their 25 degrees to 70 degrees excitatory receptive fields (some have inhibitory regions) and presumably allow the snake to orient or strike toward prey. The infrared and visual spatiotopic tectal maps have similar but not identical axes; the infrared magnification is greater than that for vision. Bimodal neurons have receptive fields for each modality that reflect the disparity of the two maps. This finding suggests that (i) during development the infrared and visual fibers spread out independently to fill available tectal sites and (ii) bimodal neurons form local connections without regard to establishing spatial correspondence between the two modalities.

Animals↗

Electrophoretic properties of esterases in chronic granulocytic leukemia.

Granulocytes were obtained from samples of peripheral blood of five patients who had untreated chronic granulocytic leukemia, and polymorphonuclear leukocytes were isolated from peripheral blood of three normal persons. Specific and nonspecific esterases were extracted from leukocyte preparations with cetyltrimethylammonium bromide and with lysolecithin, and subjected to polyacrylamide disk electrophoresis. In samples from both patients and normal persons, electrophoretic patterns of nonspecific esterase activity using alpha-naphthyl acetate and alpha-naphthyl butyrate were similar, and the esterase bands were weakly inhibited by fluoride. Lysolecithin extracts of specific esterase showed similar electrophoretic patterns for patients and normal subjects. However in cetyltrimethylammonium bromide extracts of specific esterase, 11 bands were seen in preparations from all of the patients with chronic granulocytic leukemia. In preparations of normal polymorphonuclear leukocytes, only eight bands were visualized. The results are consistent with an interpretation that these fast-moving components of specific esterase in chronic granulocytic leukemia granulocytes are present in normal polymorphonuclear leukocytes, but in quantities too small to be visualized with the technics used. Alternatively, the apparent "additional" bands of specific esterase may reflect abnormal metabolism of malignant granulocytes in chronic granulocytic leukemia.

Chronic Disease↗

Esterases in acute leukemias: a cytochemical and electrophoretic study.

Specific and nonspecific esterases were extracted from various typical cytologic types of leukemic blasts and subjected to electrophoresis in polyacrylamide gel. Preparations rich in normal granulocytes and normal monocytes were analyzed in a similar manner. The results indicated the presence of specific esterase activity in normal monocytes and in myelomonocytic and histiomonocytic leukemia, and a lack of consistent differences in the electrophoretic patterns of both specific and nonspecific esterases in these leukemias. The results support the viewpoint that distinctions between myelomonocytic and histiomonocytic leukemias cannot be made with certainty, and that they may represent variants within a broad spectrum of monocytic leukemias rather than separate and distinct entities.

Acute Disease↗

Rapid detection of ringed sideroblasts with bromchlorphenol blue.

A test for demonstrating ringed sideroblasts was developed, using the dye bromchlorphenol blue. The test is based upon the ability of the dye to form a colored water-insoluble precipitate with iron. Because it is rapid and permits localization of ferritin-containing cytoplasmic inclusions, the reaction may be useful in the assessment of sideroblastic anemias.

Anemia, Sideroblastic↗

Enzymatic abnormalities in erythroleukemia.

Enzymatic studies were performed on erythroblasts obtained from marrows of 2 patients with untreated erythroleukemia. Cytochemically, erythroblasts showed abnormalities of several enzymes involved in carbohydrate metabolism, as well as abnormalities of specific and nonspecific esterases. Electrophoretic analysis of esterases extracted from predominatly erythroid marrows showed strong moderately fluoride-resistant nonspecific esterase activity with alpha-naphthyl acetate, and weak activity with alpha-naphthyl butyrate. Isoenzymatic patterns of specific esterase activity in erythroleukemia were indistinguishable from those found in myeloblastic leukemia. The results are consistent with the concept of the Di Guglielmo syndrome in which a preleukemic erythroid disorder may precede the emergence of acute myeloblastic or myelomonocytic leukemia.

Carbohydrate Metabolism↗

Newer aspects of pernicious anemia.

Although readily treatable with vitamin B12, pernicious anemia continues to captivate investigative endeavors of those interested in the pathophysiology and pathogenesis of this disorder. Notable advances have been made in understanding properties of intrinsic factor, vitamin B12-binding proteins, structure and de novo synthesis of vitamin B12, mechanism of action of vitamin B12-dependent enzymes in man, and metabolic consequences of reduced activities of these enzymes in pernicious anemia. Similarly, newer morphological observations have given information regarding pathogenesis of some of the cytological abnormalities found in megaloblasts, and recent cytochemical studies have shed light on abnormalities of nuclear and cytoplasmic constituents in vitamin B12-deficient cells. Both cellular and humoral factors may contribute to immune-mediated processes in pernicious anemia, although as yet, it has not been established with certainty that pernicious anemia is an autoimmune disorder. As we look ahead, it will be important to define the process or processes responsible for atrophic gastritis, which is the pathophysiological basis of pernicious anemia. Likewise, advances in biophysics used in the study of cell membranes, cell surface phenomena, and metallic ion transport may find applicability in the study of pernicious anemia and perhaps provide further insights into metabolic abnormalities responsible for the development of megaloblastosis.

Anemia, Pernicious↗

William B. Castle and intrinsic factor.

Fifty years ago, William B. Castle described the properties of intrinsic factor. By so doing, he advanced the first acceptable theory of the pathogenesis and pathophysiology of pernicious anemia. Enveloping Castle's discovery were prevalent ideas in the medical community of the time, such as the importance of nutritional factors in the pathogenesis of disease, and the intriguing possibility that many disorders could be ameliorated or even cured by administration of a "missing" substance. When viewed in a contemporary perspective, Castle's observations of a half century ago are remarkable examples of ingenuity and single-minded dedication to uncovering the pathogenetic mechanism of a previously fatal disorder.

Anemia, Pernicious↗

Megakaryocytes in the giant platelet syndrome. A cytochemical and ultrastructural study.

When compared to normal megakaryocytes, those from a patient with the giant platelet syndrome exhibited numerous cytochemical abnormalities. These reflected disturbances in the metabolism of RNA, glycogen, arginine-rich histone, and various glycolytic enzymes. Ultrastructural studies of the abnormal megakaryocytes also showed decreased glycogen and RNA (ribosomes) as well as aberrations of nuclear lobulation.

Blood Platelet Disorders↗

Cytochemical identification of oxalosuccinic acid in human leukocytes.

The anthraquinone dye alizarine red S produced a unique red crystalline precipitate with oxalosuccinic acid. By chemical, colorometric and spectrophotometric analysis, this red precipitate was found to be a salt composed of these two substances, and to be insoluble in hydrochloric acid above pH = 3.2. Other biologic substances producing a red color without the formation of precipitates showed a disappearance of the red color and resumption of the yellow color of alizarine red S above pH = 3.8. On the basis of these observations, a cytochemical test was developed that may identify the site of oxalosuccinic acid in the cytoplasm of peripheral blood leukocytes. Because of the initimate association of oxalosuccinic acid with isocitric dehydrogenase, the test may also indicate the site of this enzyme as well.

Humans↗

Cytochemical detection of homocysteine in pernicious anemia and in chronic erythremic myelosis.

Utilizing a unique ability of homocysteine to form a yellow-brown precipitate with nickel chloride, a cytochemical test was developed in an effort to identify this amino acid. Among a variety of types of anemias studied, bright yellow-colored erythrocytes and erythroid precursors were found only in marrows from patients who had untreated pernicious anemia and chronic erythremic myelosis. The results of the study support the "methyltetrahydrofolate-trap" hypothesis in vitamin B12 deficiency, in which decreased activity of the methylocobalamin-dependent methyltransferase enzyme is believed to lead to accumulation of methyltetrahydrofolate and homocysteine in the deficient cells. The findings also raise the possibility that similar intracellular accumulations of homocysteine may occur in chronic erythremic myelosis, perhaps as a result of a defect in the methyltransferase enzyme.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Esterase activity in erythroleukemia.

Specific esterase activity, a property generally ascribed to cells of granulocytic origin, was found in abnormal erythroid precursors obtained from the bone marrows of six patients with untreated erythroleukemia. These erythroblasts also showed nonspecific esterase activity. Neither specific nor nonspecific esterase activity was detected in erythroid precursors obtained from the bone marrows of ten presumed normal individuals. The implications of finding specific esterase activity in the erythroblasts of erythroleukemia are discussed.

Erythroblasts↗

Periodic acid-schiff-positive megaloblasts in pernicious anemia.

Periodic acid-Schiff-positive material representing glycogen was found in bone marrow megaloblasts at all stages of maturation from 11 patients with severe untreated pernicious anemia. This accumulation of glycogen in megaloblasts, which are known to have disordered biosynthesis of DNA, RNA, and histones, suggests that carbohydrate metabolism may also be abnormal in vitamin B12 deficiency, perhaps as a result of an abnormality in the enzyme amylophosphorylase.

Anemia, Pernicious↗

Esterase reactions in acute myelomonocytic leukemia.

Specific and nonspecific esterase reactions of bone marrow cells from 14 patients with untreated acute myelomonocytic leukemia and six patients with acute histiomonocytic leukemia were examined. The technic for esterase determination permitted simultaneous visualization of both esterases on the same glass coverslip containing the marrow cells. In cases of acute histiomonocytic leukemia, monocytes, monocytoid hemohistioblasts and undifferentiated blasts stained intensely positive for nonspecific esterase, using alpha-naphthyl acetate as the substrate. No evidence of specific esterase activity using naphthol ASD-chloroacetate as the substrate and fast blue BBN as the dye coupler was apparent in these cells. In all of the cases of acute myelomonocytic leukemia, both specific and nonspecific esterases were visualized within monocytes, monocytoid cells, and granulocytic cells that had monocytoid-type nuclei. Nonspecific esterase activity was not observed in polymorphonuclear leukocytes in cases of myelomonocytic leukemia. The results support a current viewpoint that acute myelomonocytic leukemia may be a variant of acute myeloblastic leukemia, and that cytochemically, many of the leukemic cells in myelomonocytic leukemia share properties of both granulocytes and monocytes.

Acute Disease↗

Nonspecific esterase activity in pernicious anemia and chronic erythremic myelosis: a cytochemical and electrophoretic study.

Cytochemically, nonspecific esterase activity was detected in megaloblasts from three patients with severe untreated pernicious anemia, in megaloblastoid erythroblasts from five patients with chronic erythremic myelosis (DiGuglielmo syndrome), and in normoblasts from a patient with severe untreated iron-deficiency anemia. Nonspecific esterase activity in all of these erythroblasts was inhibited by sodium fluoride. Enzymatic activity could not be detected in normoblasts from normal marrows. Electrophoretically, three bands of nonspecific esterase activity could be visualized in marrow sonicates from the anemic patients and normal persons. All of these bands were inhibited by sodium fluoride. The results demonstrate that electrophoretically and in terms of fluoride inhibition, nonspecific esterases obtained primarily from erythroid precursors in various types of anemias are similar to nonspecific esterases found in normal marrows presumably containing a more heterogeneous population of cells.

Anemia, Pernicious↗

Nonspecific esterase activity in 'hairy cells'.

Nonspecific esterase activity using alpha-naphthyl butyrate as substrate was found to be present in hairy cells from patients with hairy cell leukemia. Activity of this enzyme was markedly diminished and in some instances obliterated by sodium fluoride. Since alpha-naphthyl butyrate is believed to be a more specific substrate for monocytic-type nonspecific esterase than alpha-naphthyl acetate, its presence in hairy cells combined with fluoride inhibition which is also characteristic of monocytic nonspecific esterase provides additional evidence of monocytic properties of hairy cells.

Acetates↗