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Biomedical subjects

E Silverstein

Publications and source records attributed to E Silverstein.

At least 37 records · Page 2Linked to original sources
PubMed1979

Immunofluorescent localization of angiotensin converting enzyme in epithelioid and giant cells of sarcoidosis granulomas.

Angiotensin converting enzyme (ACE) (dipeptidyl carboxypeptidase; peptidyldipeptide hydrolase, EC 3.4.15.1) was localized in epithelioid and giant cells within ACE-rich sarcoidosis granulomas, but not control granulomas, by immunofluorescence by using a rabbit anti-human ACE immunoglobulin for localization and fluorescein-labeled goat anti-rabbit immunoglobulin for detection. ACE was frequently not detected in the very central epithelioid cells, perhaps due to a paucity of cellular or molecular stimulatory interaction in this region. The results suggest that marked elevation of ACE in the granulomas and often in the serum in sarcoidosis may be due to intense induction of ACE in most epithelioid and giant cells of the sarcoidosis granulomas.

Fluorescent Antibody Technique↗
PubMed1978

Marked elevation of serum angiotension-converting enzyme and hepatic fibrosis containing long-spacing collagen fibrils in type 2 acute neuronopathic Gaucher's disease.

Serum angiotensin-converting enzyme in a patient with type 2 acute neuronopathic Gaucher's disease (242 nmol/min/ml) was 10.8 times higher than values for eight patients with other hereditary neurologic abnormalities (22.5 +/- 2.0) and 9.4 times higher than those for 12 patients with other diseases (25.7 +/- 2.6) (P less than 0.001). Serum lysozyme was not elevated in the patient with type 2 Gaucher's disease. These results indicate that elevated serum angiotensin-converting enzyme in an infant with neurologic involvement and hepatosplenomegaly is suggestive of the possibility of type 2 Gaucher's disease. Typical Gaucher's cells and fibrosis were observed by light and electron microscopy of the liver. An aspect hitherto unreported in Gaucher's disease or in the liver was that approximately 20% of the collagen fibrils were of the long-spacing type, with periodicity of 1,000 to 1,100 A and diameters of 900 to 1,500 A.

Acute Disease↗
PubMed1978

Serum and lymph-node collagenase in sarcoidosis. Comparison with angiotensin-converting enzyme.

Serum collagenase was significantly elevated in stage II, but not stage I sarcoidosis, in contrast to elevation of serum angiotensin-converting enzyme in stages I and II. Neither serum collagenase nor angiotensin-converting enzyme was elevated in active tuberculosis. Elevated serum collagenase and angiotensin-converting enzyme levels were decreased with steroid therapy. Serum collagenase and angiotensin-converting enzyme were significantly correlated but did not vary identically. Collagenase was not elevated in lymph nodes in sarcoidosis, in contrast to marked elevation of angiotensin-converting enzyme. The results suggest that serum angiotensin-converting enzyme is a more sensitive index of sarcoidosis activity than serum collagenase, which may have an ancillary role in assessment of the disease.

Humans↗
PubMed1978

Capgras syndrome-a biochemical marker?

Two cased of Capgras syndrome are reported in which platelet monoamine oxidase (MAO) activity is singificantly less than that of 24 psychiatric controls and 39 nonpsychiatric controls. This is the first report of a consistent biochemical abnormality associated with the Capgras phenomenon. Additional evidence is discussed which suggests that psychiatric patients with Capgras syndrome may belong to a discrete group of behavioral disorders characterized by reduced platelet MAO activity.

Adult↗
PubMed1978

Angiotensin-converting enzyme in macrophages and Freund's adjuvant granuloma.

Low angiotensin-converting enzyme (ACE) activity was found in rat and mouse peritoneal macrophages, in rat and rabbit pulmonary alveolar macrophages, in cultured mouse peritoneal macrophages stimulated i.p. for four days by thioglycollate, and in rabbit pulmonary alveolar macrophages stimulated in culture by 0.1 to 100 microgram/ml Salmonella typhosa endotoxin for four days. Rat subcutaneous Freund's adjuvant granulomas induced with Mycobacterium butyricum or M. tuberculosis H37 Ra contianed low ACE activity which was generally lower than that present in control tissues. Increased ACE activity in sarcoidosis and Gaucher's disease lesions does not reflect a universally high synthesis of ACE in mammalian macrophages or granulomas, but may be due to specific mechanisms.

Animals↗
PubMed1977

Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture.

Dexamethasone and prednisone in physiologic range increased angiotensin converting enzyme 7- to 16-fold in comparison to control in 3 days at maximal stimulation (4 nM steroid) in rabbit alveolar macrophages in culture. The increase was inhibited by actinomycin D (0.1 microng/ml) and 1 micronM cycloheximide, suggesting that de novo transcription and enzyme synthesis are responsible for the increased enzyme activity. This result is evidence for a regulatory mechanism for angiotensin converting enzyme, which is important in blood pressure control.

Animals↗
PubMed1977

Elevated serum and spleen angiotensin converting enzyme and serum lysozyme in Gaucher's disease.

In adult chronic non-neuronopathic (Type 1) Gaucher's disease significant (p less than 0.001) elevations of angiotensin converting enzyme in serum (93.3 +/- 14.8 nmol/min/ml; number elevated, 8/11; normal control 32.2 +/- 1.30, n = 58) and spleen (5.62 +/- 0.35 nmol/min/mg protein, n = 2; control, 0.431 +/- 0.101, n = 4) and serum lysozyme (15.6 +/- 3.37 mug/ml; number elevated, 4/5) were observed. The KM for hippuryl-L-histidyl-L-leucine of Gaucher (1.31 mM) and normal (1.23 mM) serum angiotensin converting enzyme were similar. The increased angiotensin converting enzyme (ACE) in Gaucher's disease may be related to the genetic defect resulting in increased ACE synthesis in Gaucher cells, or perhaps generally, while high lysozyme may reflect an increased body mass of reticuloendothelial cells. These enzyme elevations may be of use in suggesting the possible presence of Gaucher's disease and perhaps in assessing the magnitude of pathologic involvement.

Adult↗
PubMed1977

Sensitive fluorimetric assay for serum angiotensin-converting enzyme with the natural substrate angiotensin I.

A simple, rapid, highly sensitive and reproducible fluorimetric assay for angiotensin-converting enzyme in untreated serum using the natural substrate based on a similar assay with hippuryl-L-histidine-L-leucine is described. Angiotensin I (0.2 mM in 0.1 M potassium phosphate-30 mM NaCl, pH 7.5; 37 C) is converted to angiotensin II and L-histidyl-L-leucine, which is quantified fluorimetrically (excitation = 360 nm; fluorescence, 500 nm) by formation of a fluorescent adduct with O-phthaldialdehyde. L-Histidyl-L-leucine peptidase was also monitored in order to correct for significant activity, which was observed only once, in less than 1% sera. The mean value of serum angiotensin-converting enzyme in sera from 45 normal subjects was 4.69+/-0.194 (SEM)+/-1.30 (SD) nmol/min/ml serum, compared with 31.7+/-1.53 (SEM)+/-10.3(SD) with the substrate analog hippuryl-L-histidine-L-leucine. There was a high degree of correlation between the velocity of cleavage of angiotensin I and hippuryl-L-histidyl-L-leucine (r - 0.903 to 0.993). The assay of serum angiotensin-converting enzyme is of use in the diagnosis and possible management of sarcoidosis and Gaucher's disease, and may have other applications.

Angiotensin II↗
PubMed1977

Serum angiotensin converting enzyme in sarcoidosis: clinical significance.

The elevated activity of serum angiotensin converting enzyme (ACE) in sarcoidosis was usually reduced during steroid therapy but remained above the normal value (52 nmol-min-1-ml-1) in approximately a third of patients during the first year of therapy. ACE was elevated in 5 of 10 patients treated with steroids for at least four years. It was significantly higher in untreated patients (placebo group), who were subsequently placed on steroid therapy because of clinical deterioration, than in those remaining on placebo therapy. In general ACE tended to diminish with increasing duration of disease. The results suggest that serial study of ACE may be useful in the clinical management of sarcoidosis, including assessment of the degree of activity, the need for steroid therapy, therapeutic result and the prognosis.

Adult↗
PubMed1977

Increased serum angiotensin converting enzyme activity in sarcoidosis.

The activity of serum angiotensin converting enzyme (ACE), assayed fluorometrically with the substrate hippuryl-L-histidyl-L-leucine was significantly higher in 116 patients with sarcoidosis than in 415 patients with other diseases--pulmonary and nonpulmonary--and in 58 normal subjects. Serum ACE was elevated in 59% of 46 recently diagnosed, untreated patients with sarcoidosis and was significantly reduced following steroid therapy in three patients with sarcoidosis, but in only one of four patients treated with placebos. The results suggest that elevated serum ACE activity is a valuable, although not absolutely specific, diagnostic indicator of sarcoidosis. It should be stressed that a normal value does not rule out the disease, and that steroid therapy tends to reduce the serum ACE activity.

Adult↗
PubMed1976

Escherichia coli acetate kinase mechanism studied by net initial rate, equilibrium, and independent isotopic exchange kinetics.

The equilibrium constant of the reaction catalyzed by acetate kinase (E.C. 2.7.2.1.) was determined: K = (MgADP) (acetylphosphate)/(MgATP)(acetate) = 6.7 +/- 1.3 X 10 (-4) (pH 7.4, 25 degrees). The respective free nucleotides uncomplexed to magnesium inhibit the net reaction in both directions: competitively with the respective magnesium nucleotide (MgATP or MgADP) and noncompetitively with the co-substrate (acetate or acetylphosphate). Excess free magnesium also inhibits the net reaction in both directions. The inhibition is not competitive with the phosphoryl donor (MgATP or acetylphosphate) but is competitive with respect to the phosphoryl acceptor (acetate or MgADP). A 50-fold increase in concentration of reactants at equilibrium in 0.1 M Tris/HCl, pH 7.4, at 25 degrees resulted in a rise to plateau levels of the acetate equilibrium acetylphosphate exchange rate (measured with [U-14C]acetate) and of the ATP equilibrium ADP exchange rate (measured with [U-14C]ADP and 10-fold higher than acetate equilibrium acetylphosphate), suggesting that there is no compulsory order of binding of magnesium nucleotide and co-substrate and that all chemical transformation steps cannot be much slower than the dissociation steps. The ATP equilibrium ADP exchange rate was independent of the presence or concentration of co-substrate, whereas the acetate equilibrium acetylphosphate exchange reaction occurred only in the presence of magnesium nucleotide, and the rate was directly related to the degree of saturation of enzyme with magnesium nucleotide. The independent ATP equilibrium ADP exchange, which presumably involves a phosphoenzyme intermediate, was progressively inhibited by increasingly elevated MgADP concentrations (when MgADP/MgATP greater than or equal 5), but increasing MgATP/MgADP was not inhibitory, suggesting that MgADP may bind to nonphosphorylated as well as phosphorylated enzyme, but that MgATP cannot bind to phosphorylated enzyme. While direct transfer of the phosphoryl group between nucleotide and co-substrate in a concerted mechanism has not been ruled out, an "activated ping pong" mechanism can also be proposed which is compatible with the isotopic exchange and initial net rate kinetic results. This mechanism includes a phosphoenzyme intermediate and requires enzyme-bount MgADP for phosphorylation of the enzyme by acetylphosphate.

Acetates↗
PubMed1976

Markedly elevated angiotensin converting enzyme in lymph nodes containing non-necrotizing granulomas in sarcoidosis.

Sarcoidosis is a disease of unknown etiology that is characterized by the generalized formation of granulomas and is accompanied by elevation in the serum in less than half the patients of angiotensin converting enzyme, a dipeptidyl carboxypeptidase that catalyzes the conversion of the decapeptide, angiotensin I, to the pressor octapeptide, angiotensin II, and L-histidyl-L-leucine. Mean activity of angiotensin converting enzyme was elevated generally more than 10-fold in granuloma-containing lymph nodes, but not in lung in which normally it is abundant, in 19 of 20 patients with sarcoidosis. Angiotensin converting enzyme in lymph nodes from subjects with sarcoidosis was similar to the enzyme from normal lung and lymph node with respect to activity as a function of pH, inhibition of activity by EDTA and o-phenanthroline, gel filtration on Sephadex G-200, and requirement for chloride for activity, but appeared to be more heat labile. The data suggest that the granulomas in sarcoidosis may be the source of the elevated serum enzyme and that cells of the granulomas, particularly the epitheloid cells which appear by electron microscopy to have active protein biosynthesis, may be actively synthesizing the enzyme.

Angiotensin-Converting Enzyme Inhibitors↗