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PubMed1998

Antifungal activity of 3'-deoxyadenosine (cordycepin).

The antifungal activity of the nucleoside analog 3'-deoxyadenosine (cordycepin) was studied in a murine model of invasive candidiasis. When protected from deamination by either deoxycoformycin or coformycin, both of which are adenosine deaminase inhibitors, cordycepin exhibited potent antifungal efficacy, as demonstrated by prolongation of survival and a decrease in CFU in the kidneys of mice treated with cordycepin plus an adenosine deaminase inhibitor. The antifungal effect was seen with three different Candida isolates: Candida albicans 64, a relatively fluconazole-resistant clinical isolate of C. albicans (MIC, 16 micrograms/ml), and the fluconazole-resistant Candida krusei. Cordycepin and related compounds may provide another avenue for the discovery of clinically useful antifungal drugs.

Adenosine Deaminase Inhibitors↗
PubMed1984

Transmethylation inhibitors decrease chemotactic sensitivity and delay cell aggregation in Dictyostelium discoideum.

In Dictyostelium discoideum, extracellular cyclic AMP (cAMP) induces chemotaxis and cell aggregation. Suspensions of cAMP-sensitive cells respond to a cAMP pulse with a rapid, transient increase of protein carboxyl methylation. The transmethylation inhibitors cycloleucine, L-homocysteine thiolactone, and coformycin decrease chemotactic sensitivity and delay cell aggregation when administered in concentrations which do not influence cAMP binding to cell surface receptors or the activity of total phosphodiesterase. The ability of the drugs to inhibit chemotaxis could be correlated with their capacity to convert the initial transient positive response of carboxyl methylation to cAMP into a negative one. This suggests that both protein O-methyltransferase and protein methylesterase are activated after stimulation of aggregative cells with cAMP, the net effect being a transient, positive response of methylation. In the presence of a sufficiently large dose of inhibitor, methyltransferase is inhibited, whereas methylesterase activity is much less affected, so that a transient negative response of methylation to cAMP is observed. The slow, positive response of carboxyl methylation to cAMP which occurs ca. 2.5 to 5 min after stimulus administration is not affected by inhibitors of transmethylation. These results suggest that methylation reactions are involved in the chemotactic response of D. discoideum cells to cAMP.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Renal ammonia excretion and production in goldfish, Carassius auratus, at low environmental pH.

Renal ammonia excretion and production were investigated in normal and acidotic goldfish (Carassius auratus). Goldfish were made acidotic by exposure to a low pH environment (pH 4.0), which caused a lowering of blood pH from 7.88 to 7.61. Environmental acidification resulted in an increase in total renal ammonia excretion (from 0.43 to 1.00 mueq X 100 g-1 X h-1) and urinary concentration (from 0.58 to 0.76 mM), as well as a rise in renal titratable acid output (from -0.57 to +0.62 mueq X 100 g-1 X h-1). The acidotic fish showed a rise in urine flow that was due to an increased glomerular filtration rate. In vitro studies demonstrated the capacity for renal ammonia formation from aspartate, alanine, glutamine, glutamate, and glycine. The relatively high level of glutamate in the renal tissue suggested that the generation of ammonia from these amino acids occurs via the formation of glutamate, either by deamidation of glutamine or transdeamination of aspartate and alanine. Both ammonia production by isolated renal tubules and individual enzyme assays in kidney homogenates indicated that aspartate has the greatest potential as a renal ammonia precursor in vitro. The purine nucleotide cycle, investigated with the use of the inhibitor coformycin, does not appear to contribute to ammonia production in the kidney of this species.

Acidosis↗
PubMed1977

Enhancement of the biological activity of adenosine analogs by the adenosine deaminase inhibitor 2'-deoxycoformycin.

The potent adenosine deaminase inhibitor 2'-deoxycoformycin ((R)-3-(2-deoxy-beta-D-erythropentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol) inhibits the enzymic inactivation and potentiates the cytotoxic activity of a variety of adenosine analogs in the P388 murine leukemia cell culture system. The activity of all seven adenosine analogs examined was enhanced by 2'-deoxycoformycin with the exception of tubercidin (7-deaza-adenosine) which is not a substrate for the deaminase. In vivo, 2'-deoxy-coformycin potentiated the antineoplastic activity of 9-beta-D-xylofuranosyladenine in mice with P388 murine leukemia.

Adenosine↗
PubMed1976

Purine nucleoside metabolism in the erythrocytes of patients with adenosine deaminase deficiency and severe combined immunodeficiency.

Deficiency of erythrocytic and lymphocytic adenosine deaminase (ADA) occurs in some patients with severe combined immunodeficiency disease (SCID). SCID with ADA deficiency is inherited as an autosomal recessive trait. ADA is markedly reduced or undetectable in affected patients (homozygotes), and approximately one-half normal levels are found in individuals heterozygous for ADA deficiency. The metabolism of purine nucleosides was studied in erythrocytes from normal individuals, four ADA-deficiency patients, and two heterozygous individuals. ADA deficiency in intake erythrocytes was confirmed by a very sensitive ammonia-liberation technique. Erythrocytic ADA activity in three heterozygous individuals (0.07,0.08, and 0.14 mumolar units/ml of packed cells) was between that of the four normal controls (0.20-0.37 mumol/ml) and the ADA-deficient patients (no activity). In vitro, adenosine was incorporated principally into IMP in the heterozygous and normal individuals but into the adenosine nucleotides in the ADa-deficient patients. Coformycin (3-beta-D-ribofuranosyl-6,7,8-trihydroimidazo[4,5-4] [1,3] diazepin-8 (R)-ol), a potent inhibitor of ADA, made possible incorporation of adenosine nucleotides in the ADA-deficient patients...

Adenosine Deaminase↗
PubMed2003

Special sensitization pattern in adenosine-induced myocardial responses after thyroxine-treatment.

Chronic thyroxine treatment reduces the susceptibility of atrial myocardium to adenosine. While the possible role of membrane adenosine receptors in this action is supported by several studies, the involvement of intracellular adenosine mechanisms has not been defined. The present experiments were carried out in electrically driven euthyroid and hyperthyroid guinea pig atrial myocardium. The extracellular and intracellular actions of adenosine were analyzed pharmacologically by the use of specific blockers of membrane adenosine transport and intracellular adenosine deaminase (ADA). The involvement of phosphoprotein phosphatase, phospholamban, and sarcoplasmic reticulum Ca2+ ATPase (SERCA) in the adenosine-induced responses was also studied. The major findings were as follows: i) pD(2)- and E(max)-values for adenosine-induced decrease of mechanical activity were significantly reduced after an 8-day thyroxine treatment in atrial tissues; ii) in atria of thyroxine-treated animals, membrane purine transport inhibitors (dipyridamole, NBTI) induced similar leftward shifts in concentration-response curves for adenosine in both euthyroid and hyperthyroid atrial myocardium without altering the depressed E(max) values; iii) the leftward displacement evoked by inhibitors of intracellularly located ADA (coformycin, EHNA) was more striking in hyperthyroid than euthyroid myocardia. ADA inhibitors induced a complete reversal of the maximum adenosine actions; iv) inhibition by cantharidin of phosphoprotein phosphatases (after inhibition of ADA) reduced the adenosine-induced responses. This inhibition was stronger in hyperthyroid atria; v) pharmacological elimination of sarcoplasmic reticulum Ca2+ ATPase by cyclopiazonic acid did not alter the cardiac responses to adenosine and this was independent of thyroid status. It is suggested that distinct modulation of the extra- and intracellular adenosine actions is present in eu- and hyperthyroid hearts. In the latter, a predominance of intracellular adenosine mechanisms can be proposed.

Adenosine↗
PubMed1988

Enzymes of adenosine metabolism in mouse sperm suspensions.

The enzymes of adenosine metabolism were investigated in suspensions of epididymal mouse spermatozoa incubated under conditions which support capacitation in vitro. High levels of adenosine deaminase activity were found in sperm suspensions, but the enzyme was located in the surrounding medium and was not intrinsic to spermatozoa. 5'-Nucleotidase was also present in the surrounding medium while in sperm cells it existed as an ecto-enzyme. Adenosine was not metabolized by washed spermatozoa under conditions used for the assay of adenosine deaminase or adenosine kinase, but it was metabolized rapidly by unwashed sperm suspensions. Incubation of sperm suspensions in conditions which modulate fertilizing ability resulted in small alterations in intrinsic 5'-nucleotidase activity of spermatozoa. In contrast, the activity of adenosine deaminase was not consistently modulated by such manipulations. Adenosine deaminase and 5'-nucleotidase exhibited similar kinetic parameters to enzymes from other sources and their activities were inhibited by coformycin and alpha, beta-methylene adenosine 5'-diphosphate, respectively. These studies highlight the low adenosine-metabolizing ability of spermatozoa coupled with the extensive metabolism in the medium which surrounds them. Extracellular adenosine metabolism can therefore occur and may modulate capacitation in vitro.

5'-Nucleotidase↗
PubMed1975

Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis, and glucose metabolism of fat cells.

In fat cells isolated from the parametrial adipose tissue of rats, the addition of purified adenosine deaminase increased lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. Adenosine deaminase markedly potentiated cyclic AMP accumulation due to norepinephrine. The increase in cyclic AMP due to adenosine deaminase was as rapid as that of theophylline with near maximal effects seen after only a 20-sec incubation. The increases in cyclic AMP due to crystalline adenosine deaminase from intestinal mucosa were seen at concentrations as low as 0.05 mug per ml. Further purification of the crystalline enzyme preparation by Sephadex G-100 chromatography increased both adenosine deaminase activity and cyclic AMP accumulation by fat cells. The effects of adenosine deaminase on fat cell metabolism were reversed by the addition of low concentrations of N6-(phenylisopropyl)adenosine, an analog of adenosine which is not deaminated. The effects of adenosine deaminase on cyclic AMP accumulation were blocked by coformycin which is a potent inhibitor of the enzyme. These findings suggest that deamination of adenosine is responsible for the observed effects of adenosine deaminase preparations. Protein kinase activity of fat cell homogenates was unaffected by adenosine or N6-(phenylisopropyl)adenosine. Norepinephrine-activated adenylate cyclase activity of fat cell ghosts was not inhibited by N6-(phenylisopropyl)adenosine. Adenosine deaminase did not alter basal or norepinephrine-activated adenylate cyclase activity. Cyclic AMP phosphodiesterase activity of fat cell ghosts was also unaffected by adenosine deaminase. Basal and insulin-stimulated glucose oxidation were little affected by adenosine deaminase. However, the addition of adenosine deaminase to fat cells incubated with 1.5 muM norepinephrine abolished the antilipolytic action of insulin and markedly reduced the increase in glucose oxidation due to insulin. These effects were reversed by N6-(phenylisopropyl)adenosine. Phenylisopropyl adenosine did not affect insulin action during a 1-hour incubation. If fat cells were incubated for 2 hours with phenylisopropyl adenosine prior to the addition of insulin for 1 hour there was a marked potentiation of insulin action. The potentiation of insulin action by prior incubation with phenylisopropyl adenosine was not unique as prostaglandin E1, and nicotinic acid had similar effects.

Adenosine↗
PubMed1991

Roles of adenosine and theophylline on the recovery of adenine nucleotides in postischemic cultured renal tubular cells.

The effect of adenosine (ADO) on the recovery of cellular adenine nucleotides (AN) was evaluated in the cultured cells deprived of oxygen and substrates (ischemia) and in nonischemic cells (control). The primary cultured cells were obtained from microdissected rabbit proximal straight tubules. Ten-day-old cultured cells were made ischemic for 6 hr, and allowed to recover for 24 hr. At the end of ischemia, cells were incubated with ADO, theophylline (T), dipyridamole (D), coformycin (C) or combined agents for 3 hr. Total AN (TAN) were determined after 3 and 24 hr of recovery. The results, after 3 hr of incubation, suggest that in both control and ischemic cells, ADO is taken up by cultured cells and is preferentially converted to nucleotides. This effect is blocked by D, which inhibits ADO uptake, uninfluenced by C, which inhibits ADO deaminase and potentiated by T, which inhibits 5'-nucleotidase. After 24 hr of recovery, the beneficial effects of ADO alone or combined D, C, or T, on TAN were not seen in control cells. In contrast, in the ischemic cells, after 24 hr of recovery, ADO + T normalized ATP, ADP and TAN to the preischemic levels. T alone significantly increased ATP after 24 hr of recovery. To demonstrate further that the beneficial effect of T is due to inhibition of 5'-nucleotidase, cells were treated with adenosine alpha, beta-methylene diphosphate in the same manner as T. Combined ADO + adenosine alpha, beta-methylene diphosphate normalized ATP, ADP and TAN after 24 hr of recovery. This finding suggests that inhibition of 5'-nucleotidase improves postischemic AN.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1978

Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine.

Deoxyadenosine but not adenosine reversed the antiviral activity of 9-beta-D-arabinofuranosyladenine (ara-A) and 9-beta-D-arabinofuranosylhypoxanthine (ara-H) when used in the presence of coformycin, an inhibitor of adenosine deaminase. In suspension cultures of KB cells, 10 muM ara-A inhibited the replication of herpes simplex virus type 1 by 80%. Concomitant addition of 50 muM deoxyadenosine reduced the antiviral activity of 10 muM ara-A to only 40% inhibition. Adenosine failed to antagonize the antiviral activity. In monolayer cultures of KB cells, the 50% inhibitory concentration of ara-A was increased from 1.5 to 2.9 muM by 2 muM deoxyadenosine and to 8.5 muM by 10 muM deoxyadenosine. Analysis of the dose-response data by a double reciprocal plot method indicated that the antagonism was competitive. The antiviral activity of ara-H also was antagonized by deoxyadenosine. The 50% inhibitory concentration of ara-H was increased from 42 muM to 70, 91, or 121 muM by the concurrent addition of 5, 10, or 20 muM deoxyadenosine. Competitive antagonism could not be demonstrated. In the absence of the adenosine deaminase inhibitor, neither ara-A nor ara-H was antagonized by deoxyadenosine. Since such inhibitors were not available unitl recently, previous investigators were unable to observe the antagonistic capacity of deoxyadenosine.

Adenosine↗
PubMed1987

[Overview of ATL (adult T-cell leukemia) research].

ATL is a unique T-cell malignancy first described by Takatsuki and colleagues in 1970s. We estimate that more than 300 patients a year have been detected in the endemic areas of Kyushu, Japan. The surface phenotype of ATL cells characterized by monoclonal antibodies is T3+, T4+, T8-, T11+ and Tac+. In all cases the serum is positive for anti-HTLV-I antibodies and the ATL cells contain the proviral DNA of HTLV-I. Variations in the clinical features of atypical ATL suggested a division of the spectrum of ATL into five types: acute; chronic; smoldering; crisis; and lymphoma. Typical ATL takes an acute course. The survival time is short, with 50% mortality within approximately 5 months. In general a poor prognosis is indicated by the elevation of serum lactate dehydrogenase, calcium, and bilirubin, as well as by high WBC. Smoldering ATL is characterized by the presence of a few abnormal cells (0.5%-3%) in the peripheral blood over a long period. Crisis in chronic or smoldering ATL means the progression of the disease to acute ATL. The lymphoma type of ATL is considered to be a form of T-cell-type non-Hodgkin's lymphoma in which malignant cells contain proviral DNA of HTLV-I. Screening of the sera from healthy adults for presence of the anti-HTLV-I antibodies revealed that 3.6% of healthy individuals in Kumamoto Prefecture, which is located in the middle of Kyushu, were HTLV-I carriers. Family studies showed that the routes of natural infection of HTLV-I are from mother to child and also from husband to wife. The borderline between the healthy carrier state and smoldering ATL remains unclear. Smoldering ATL is frequently diagnosed in patients with fungus infection of the skin, chronic lymphadenopathy, interstitial pneumonitis, chronic renal failure and strongyloidiasis. Five patients with ATL refractory to conventional chemotherapeutic agents were treated with 2'-deoxy-coformycin (DCF), a potent inhibitor of adenosine deaminase. Two patients showed a good response, and three were resistant to DCF. In addition our experiences with a concurrence of lymphoma-type ATL in three sisters and spontaneous remissions in a patients with chronic ATL will be referred.

Carrier State↗
PubMed1988

Adenosine, deoxyadenosine, and deoxyguanosine induce DNA cleavage in mouse thymocytes.

When thymocytes were cultured with adenosine, deoxyadenosine, or deoxyguanosine at 1 mM for 24 h, DNA cleavage at internucleosomal sites with multiples of approximately 180 bp was induced, followed by lactate dehydrogenase release into the medium. In the presence of coformycin, an adenosine deaminase inhibitor, or formycin B, a purine nucleoside phosphorylase inhibitor, DNA cleavage was induced by these nucleosides at concentrations of less than 50 microM. Other purine and pyrimidine ribo- and deoxyribonucleosides did not induce DNA cleavage or LDH release. Because thymocyte nuclei contain a Ca2+,Mg2+-dependent endonuclease, which preferentially cuts DNA in its linker regions, DNA fragmentation induced by the three purine nucleosides was suggested to occur through increased activity of the endonuclease. The DNA cleavage induced by the nucleosides required protein phosphorylation and synthesis, inasmuch as it was inhibited by an inhibitor of protein kinases, H-7, and by an inhibitor of protein synthesis, cycloheximide. The inhibition of DNA cleavage was accompanied by a reduction in lactate dehydrogenase release, suggesting a causal relationship between DNA cleavage and cell death. The DNA cleavage and subsequent cell lysis might be related to the selective thymocyte deletion observed in patients with adenosine deaminase or purine nucleoside phosphorylase deficiency.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1978

Relationships of adenine nucleotide metabolism to platelet-collagen adhesion.

Adhesion of platelets to collagen fibrils in a stirred system was inhibited by preincubation of platelets with combinations of 2-deoxy-D-glucose and oligomycin or antimycin. The inhibition of adhesion was associated with a decrease in metabolic ATP to 6% of control levels. Without metabolic inhibitors, platelets adherent to collagen fibrils were found to have catabolized approximately 57% of their metabolic ATP, and converted a major part of this to IMP. Storage pool ATP and ADP contents were also diminished in the adherent platelets. Pretreatment with imipramine resulted in 76% inhibition of the release reaction, but only 5% inhibition of adhesion. Imipramine-treated platelets that were adherent to collagen showed significant depletion of metabolic ATP, but markedly diminished conversion of ATP to IMP as compared to control adherent platelets. Inhibition of deamination of platelet AMP by coformycin or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) did not inhibit adhesion, although platelets adherent to collagen after treatment with these agents showed depletion of metabolic ATP. These studies suggest that adhesion is an energy dependent process, occurring independently of release, and not associated with conversion of ATP to IMP. The energy dependent portions of the adhesion process are probably disc to sphere transformation and pseudopod formation, the ATP threhold requirement is relatively low, and the ATP utilized can probably be regenerated during the adhesion process via glycolysis and oxidative phosphorylation.

Adenine Nucleotides↗
PubMed1982

Biochemical correlates of the differential sensitivity of subtypes of human leukemia to deoxyadenosine and deoxycoformycin.

Leukemic cells incubated in vitro with 2'-deoxyadenosine (dAdo) plus an inhibitor of adenosine deaminase, 2'-deoxy-coformycin (DCF), show different metabolic responses depending on the histologic and immunologic type of the leukemia. Leukemic cells were obtained from 54 patients with acute lymphoblastic leukemia (ALL), 9 with myeloid or nonlymphoblastic leukemia, 3 with chronic lymphocytic leukemia (CLL), and 3 with lymphoma. There was a wide variation in the LD50, the concentration of dAdo that caused 50% inhibition of the incorporation of 3H-thymidine into cells in the presence of 20 microM DCF. T-cell leukemia specimens were much more sensitive to dAdo than were specimens of pre-B-ALL and null-ALL. In leukemic cells that had been incubated with 14C-dAdo plus DCF, a good correlation was observed between the LD50 and the ratio of 14C-deoxyATP to ATP (correlation coefficient for the fit to a hyperbola = 0.853). The accumulation of deoxyATP by the leukemic cell specimens was correlated best with the activity of ecto-ATPase, less well with cytoplasmic 5'-nucleotidase and deoxyadenosine kinase, and poorly with adenosine deaminase and ecto-5'-nucleotidase. The clinical response to DCF therapy of a patient with T-ALL and another with pre-B-ALL was consistent with the in vitro metabolic response of their cells to DCF and dAdo.

Adenosine Deaminase↗
PubMed1983

Studies on the mechanism of adenosine transport in Trypanosoma vivax.

Adenosine uptake in the presence of some metabolic inhibitors and nucleosides has been studied. The uptake of adenosine was inhibited by oubain, phlorizin, iodoacetate and coformycin. Guanosine, on the other hand stimulated adenosine uptake to a considerable extent. Neither thymidine nor inosine caused significant change in adenosine uptake. Results of the time course assay and uptake studies at various concentrations of adenosine suggest that possibly more than one mode of uptake operates in the transport of adenosine in T. Vivax.

Adenosine↗
PubMed1994

Adenosine inhibits the adhesion of anti-CD3-activated killer lymphocytes to adenocarcinoma cells through an A3 receptor.

We have investigated the hypothesis that adenosine, a purine nucleoside produced within hypoxic regions of solid tumors, may interfere with the recognition of tumor cells by cytolytic effector cells of the immune system. We measured the adhesion of murine spleen-derived anti-CD3-activated killer (AK) lymphocytes to syngeneic MCA-38 colon adenocarcinoma cells in a model system. Adenosine, in the presence of the adenosine deaminase inhibitor coformycin to prevent the breakdown of adenosine, inhibited adhesion by up to 60%. The inhibitory effect of adenosine was exerted on the AK cells and not on the MCA-38 targets. The response to adenosine was generated at the cell surface, since the inhibition of adhesion was not abrogated by S-(4-nitrobenzyl)-6-thioinosine or dipyridamole, which block adenosine uptake. The inhibition of adhesion due to adenosine was not blocked by either the A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine or the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine. This suggested that a non-A1, A2 receptor might be involved. The relative order of potencies of adenosine and common analogues was: 5'-N-ethylcarboxamidoadenosine = adenosine = (R)-phenylisopropyladenosine > N6-cyclopentyladenosine > 2-chloro-N6-cyclopentyladenosine = 2-p-(2- carboxyethyl)phenethylamino-5'-N-ethyl-carboxamidoadenosine. This agonist potency profile was again inconsistent with either the A1 or the A2 receptor subtype but indicated that the recently described A3 receptor subtype might be responsible for the inhibition of adhesion. Consistent with this suggestion, aminophenylethyladenosine, an adenosine analogue that binds with high affinity to A3 receptors, inhibited the adhesion of AK cells to MCA-38 tumor cells with high potency (50% inhibitory concentration approximately 1 nM). Adenosine, therefore, interferes with the AK cell recognition of colorectal tumor targets by acting through an A3 receptor on the effector cells. We suggest that this mechanism of immunosuppression, secondary to tissue hypoxia, may be important in the resistance of colorectal and other solid cancers to immunotherapy.

Adenocarcinoma↗
PubMed1993

Yeast AMP deaminase. Catalytic activity in Schizosaccharomyces pombe and chromosomal location in Saccharomyces cerevisiae.

The AMP deaminase gene was mapped to chromosome XIII of Saccharomyces cerevisiae strain JM1901. The AMP deaminase gene is located near SUP5, GAL80, SUF7, and SUF22. The presence of AMP deaminase in the fission yeast Schizosaccharomyces pombe was examined by comparing DNA hybridization, protein immunoreactivity, and catalytic activity from S. cerevisiae, known to contain the protein, to S. pombe. DNA hybridization experiments using the cloned S. cerevisiae AMP deaminase gene failed to hybridize to the genomic DNA from S. pombe strain 972h-s. Protein extracts from S. pombe and S. cerevisiae were analyzed in parallel and exhibited comparable AMP deaminase activities. Analysis of reaction intermediates in cell extracts of S. pombe established that IMP is formed directly from AMP without intervening steps. The AMP deaminase of S. pombe was purified 1,100-fold to a specific catalytic activity of 67 mumol/min/mg of protein. Purified protein interacted weakly with polyclonal antibodies prepared against S. cerevisiae AMP deaminase. AMP deaminases from both S. cerevisiae and S. pombe were activated by ATP with micromolar activation constants, are inhibited by coformycin, and are specific for AMP when compared to other purine nucleosides and nucleotides. The results establish that S. pombe contains an AMP deaminase with catalytic properties similar to that from S. cerevisiae, even though the DNA sequences of the genes and the immunoreactivity of the protein from S. pombe differs considerably from the AMP deaminase of S. cerevisiae. Genetic analysis of the pathways of purine metabolism in S. pombe (Pourquié, J., and Heslot, H. (1971) Genet. Res. 18, 33-44) had indicated the absence of AMP deaminase. The presence of a regulated AMP deaminase in S. pombe supports the hypothesis that eukaryotes regulate adenine nucleotide pools by the activity of AMP deaminase.

AMP Deaminase↗
PubMed1997

[Primary cutaneous lymphoma--mycosis fungoides].

Malignant lymphoma of the skin is a type of extranodal lymphoma with a benign prognosis, in which the main organ involved is the skin. Some 80-90% of the cases in Japan show a T-cell phenotype. Mycosis fungoides and Sézary syndrome are common T-cell lymphomas of the skin. The tumor cells of mycosis fungoides, small and medium-sized cells with cerebriform nuclei, are detected in an epidermo-dermo junction. The tumor cells show CD3, CD4 and CLA, (cutaneous lymphocyte associated antigen) positivity. Various forms of topical therapy, such as topical steroid, photochemotherapy (PUVA), and interferons, have been indicated for the good-risk group (stages I A, I B and II A). Electron-beam irradiation, various chemotherapy, such as low-dose etoposide, low-dose MTX and CPT-11 and deoxy coformycin (DCF) plus IFNs, have been indicated for intermediate-risk group (stage II B, III and IV A). BRMs plus low-dose etoposide, electron-beam irradiation and a multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, have been indicated for the high-risk group (stages IV A and IV B). Cutaneous B cell lymphoma (CBCL) can be diagnosed using a molecular biological assay. The tumor cells of CBCL do not express T-cell antigens such as CD2, CD3 and CD43 and show B-cell antigens such as sIg, CD19, CD20 and CD22. Electron-beam irradiation has been indicated for early-stage CBCL (stages I and II). An effective multiagent combination chemotherapy, such as MACOP-B, M-BACOD or ProMACE-CytaBOM, is required for patients with advanced stage CBCL (stages III and IV).

Antigens, CD↗