Biomedical subjects

F Marumo

Publications and source records attributed to F Marumo.

At least 415 records · Page 23Linked to original sources

PubMed1993

Enhanced coagulation and fibrinolysis during treatment with recombinant human erythropoietin in patients undergoing chronic hemodialysis.

Twenty-two patients on regular hemodialysis treatment suffering from renal anemia were treated with intravenous recombinant human erythropoietin (rhEPO) for more than 8 weeks. Before and 4 and 8 weeks after the start of rhEPO administration, we measured prothrombin time, activated partial thromboplastin time, fibrinogen (FBG), antithrombin III activity (ATIII), plasminogen activity (PLG), alpha 2-plasmin inhibitor activity (alpha 2 PI), alpha 2-plasmin inhibitor-plasmin complex (alpha 2 PIC), and cross-linked fibrin degradation products (XL-FDP) in citrated plasma to determine whether rhEPO treatment enhances coagulation and fibrinolytic activity. The pretreatment values of FBG, alpha 2 PIC, and XL-FDP were significantly higher than the normal control values. The pretreatment values of ATIII, PLG, and alpha 2 PI were significantly lower than the normal control values. Platelet count and FBG were significantly increased 4 and 8 weeks after treatment with rhE-PO. The prothrombin time was significantly shortened 8 weeks after rhEPO treatment, but the activated partial thromboplastin time did not change. PLG was significantly decreased 4 and 8 weeks after rhEPO treatment, and ATIII and alpha 2 PI were significantly decreased 8 weeks after rhEPO treatment. alpha 2 PIC was significantly increased 8 weeks after rhEPO treatment, and XL-FDP was significantly increased 4 and 8 weeks after rhEPO treatment. These data suggest that in patients on regular hemodialysis treatment coagulation and fibrinolysis are already enhanced before the start of rhEPO treatment and that rhEPO administration further enhances these disorders.

Adult↗

PubMed1993

Decreased lithium clearance in patients with hyperthyroidism.

Lithium clearance was studied to investigate proximal tubular function in patients with hyperthyroidism (n = 10) and control subjects (n = 7). Patients with hyperthyroidism showed significantly reduced fractional excretion of lithium (FELi) compared with control subjects (15.0 +/- 1.5%, n = 10, vs. 23.7 +/- 0.6%, n = 7, means +/- SE, p < 0.001). The reduced FELi of the hyperthyroid state was reversed toward control values with treatment by antithyroid drugs (12.6 +/- 2.6 toward 26.8 +/- 2.5% for 5 patients, means +/- SE). Tubular reabsorption of phosphate (TRP) was significantly increased in hyperthyroid patients compared with control subjects (96.1 +/- 0.7 vs. 87.5 +/- 0.7%, p < 0.001), and it returned to control values after the treatment. Our data demonstrate that lithium clearance is decreased and TRP is increased in patients with hyperthyroidism, which suggests that proximal tubular reabsorption of sodium and TRP is increased in hyperthyroidism.

Adult↗

PubMed1993

Insulin-like growth factor-I induces hypertrophy with enhanced expression of muscle specific genes in cultured rat cardiomyocytes.

BACKGROUND: Cardiac hypertrophy is commonly observed in acromegalic patients, in whom serum insulin-like growth factor-I (IGF-I) levels are elevated. In the present study, we examined whether IGF-I induces hypertrophy in cultured neonatal rat cardiomyocytes through its specific receptor and whether IGF binding protein-3 (IGFBP-3), which is a major circulating carrier protein for IGF-I, inhibits IGF-I-induced cardiac hypertrophy in vitro. METHODS AND RESULTS: Because the response of cardiac hypertrophy is characterized by the induction of expression for muscle-specific genes, the effect of IGF-I on steady-state levels of mRNA for myosin light chain-2 (MLC-2) and troponin I and for skeletal and cardiac alpha-actin isoforms was evaluated by Northern blot analysis. IGF-I (10(-7) M) increased mRNA levels for MLC-2 and troponin I as early as 60 minutes with maximum levels by 6 hours, which were maintained for as long as 24 hours. IGF-I (10(-7) M) also increased transcripts for skeletal alpha-actin but not for cardiac alpha-actin. The cell size as evaluated morphometrically was almost doubled after 48-hour treatment with IGF-I. IGF-I induction of protein synthesis was dose dependent (10(-10) to 10(-7) M) with a maximal 2.2-fold increase seen at 10(-8) M. In contrast to the hypertrophic effect of IGF-I, growth hormone affected neither protein synthesis nor expression for muscle-specific genes. Binding study using 125I-IGF-I revealed the presence of specific binding sites for IGF-I in rat cardiomyocytes. IGFBP-3 induced a dose-dependent inhibition of protein synthesis stimulated by IGF-I; IGFBP-3 (10(-7) M) completely inhibited the [3H]leucine uptake stimulated by IGF-I (10(-8) M). IGFBP-3 similarly inhibited the IGF-I-stimulated gene expressions for MLC-2 and troponin I. CONCLUSIONS: These results suggest that IGF-I directly causes cardiac hypertrophy and that its effect can be blocked by IGFBP-3.

Actins↗

PubMed1993

Heparin has an inhibitory effect on endothelin-1 synthesis and release by endothelial cells.

We studied the inhibitory effects of heparin on basal and agonist-induced endothelin-1 biosynthesis and release from cultured bovine endothelial cells. Heparin dose-dependently and similarly inhibited endothelin-1 release, inositol trisphosphate production, and intracellular free Ca2+ levels stimulated by thrombin. Hirudin fragment had an inhibitory effect on thrombin-induced endothelin-1 release, whereas anti-thrombomodulin antibody had no effect. Heparin completely blocked phorbol ester-induced endothelin-1 release, whereas it had a partial inhibitory effect on endothelin-1 release stimulated by angiotensin and vasopressin. Northern blot analysis using complementary DNA for bovine preproendothelin-1 as a probe revealed that heparin reduced not only the basal but also the stimulated expression of preproendothelin-1 messenger RNA by thrombin and phorbol ester. These data suggest that heparin, in addition to its antithrombin effect, has an inhibitory effect on the biosynthesis and release of endothelin-1, possibly by inhibiting protein kinase C-dependent pathway.

Animals↗

PubMed1993

Induction of nitric oxide synthase gene by interleukin in vascular smooth muscle cells.

To elucidate whether cytokines induce nitric oxide synthase in vascular smooth muscle cells, we studied the effects of human recombinant interleukin-1 beta on the synthesis and release of nitric oxide in cultured rat vascular smooth muscle cells by measurement of NO2-/NO3- levels. Furthermore, we performed Northern blot analysis using subcloned polymerase chain reaction products as probes for constitutive and inducible nitric oxide synthase. Interleukin-1 beta dose dependently (1 to 20 ng/mL) stimulated NO2-/NO3- production as a function of time. Northern blotting demonstrated the interleukin-1 beta-induced expression of messenger RNA for an inducible but not for the constitutive nitric oxide synthase after 3 hours. NG-Monomethyl L-arginine completely blocked the interleukin-1 beta-induced NO2-/NO3- production, the effect of which was reversed by L-arginine but not by D-arginine. Dexamethasone inhibited the interleukin-1 beta-induced NO2-/NO3- production in a dose-dependent manner (10(-9) to 10(-7) M) and the interleukin-1 beta-inducible nitric oxide synthase messenger RNA levels. Neither a calmodulin inhibitor (W-7) nor a protein kinase C inhibitor (staurosporine) showed any effects on the induction of nitric oxide synthase transcripts or production of NO2-/NO3- stimulated by interleukin-1 beta, whereas cycloheximide and actinomycin D completely inhibited the basal and stimulated NO2-/NO3- production. These data demonstrate for the first time that interleukin-1 beta induces gene expression of inducible nitric oxide synthase and its de novo protein synthesis in rat vascular smooth muscle cells, thereby leading to generation of nitric oxide via Ca2+/calmodulin-independent and protein kinase C-independent mechanisms.

Alkaloids↗

PubMed1993

Respiratory control during exercise in patients with cardiovascular disease.

The pathophysiologic mechanism for exertional dyspnea, the main symptom of patients with heart failure, has not been fully clarified. To determine the relationship between exercise hyperpnea and the lactic acidosis in patients with heart failure, we evaluated ventilation during incremental exercise both below and above the lactic acidosis threshold in 16 normal subjects and in 48 patients with cardiovascular disease while expired gas was analyzed continuously. The peak oxygen uptake and oxygen uptake at the lactic acidosis threshold decreased significantly as the New York Heart Association (NYHA) functional class severity increased. the slope of the increase in ventilation to the increase in oxygen uptake (delta VE/delta VO2) at work rates below the lactic acidosis threshold did not differ between normal subjects and patients with heart failure. Above the lactic acidosis threshold, however, the slope of delta VE/delta VO2, which was higher than that below the lactic acidosis threshold in each of four groups, was steeper in patients in NYHA Class II (60.8 +/- 17.9) and Class III (66.5 +/- 21.2) when compared with that in the normal subjects (46.6 +/- 13.5) or the patients in NYHA Class I (46.1 +/- 10.3). The lactic acidosis caused by decreased oxygen transport to working muscles accounts for the higher ventilation during exercise in cardiac patients. These data suggest that the increased ventilation during exercise, which must be related to exertional dyspnea, in patients with cardiovascular disease is primarily the consequence of a stimulus to regulate arterial pH.

Acidosis, Lactic↗

PubMed1993

Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells.

Endothelins (ET) produce endothelium-dependent vasodilation through nitric oxide (NO) synthesis. The present study was designed to elucidate the cellular mechanism by which ET induces synthesis and release of endothelium-derived NO by cultured bovine endothelial cells (EC). Binding studies revealed that bovine EC membrane had the binding sites of a novel agonist (BQ3020) for non-isopeptide-selective receptor subtype (ETB). Affinity labeling studies showed a major labeled band with the apparent molecular mass of 50 kD. Northern blot analysis demonstrated the expression of mRNA for ETB receptor. BQ3020 rapidly and dose dependently induced formation of inositol-1,4,5-triphosphate and increased intracellular Ca2+ concentrations in fura-2-loaded cells. Concomitantly, BQ3020 dose dependently stimulated production of both nitrate/nitrite (NOx) and cyclic GMP; a highly significant correlation existed between NOx and cGMP production. The stimulatory effect on NOx and cGMP production by ETB agonist was inhibited by NO synthase inhibitor monomethyl-L-arginine; this effect was reversed by coaddition of L-arginine, but not D-arginine. NOx and cGMP production stimulated by BQ3020 was inhibited by pretreatment with pertussis toxin. ETB agonist-induced NOx production was blocked by a calmodulin inhibitor and an intracellular Ca2+ chelator, but not by an extracellular Ca2+ chelator or a Ca2+ channel blocker. These data suggest that endothelins stimulate ETB receptor-mediated phosphoinositide breakdown via pertussis toxin-sensitive G-protein(s), which triggers release of intracellular Ca2+, thereby activating Ca2+/calmodulin-dependent NO synthase in EC.

Amino Acid Oxidoreductases↗

PubMed1993

Different localization and regulation of two types of vasopressin receptor messenger RNA in microdissected rat nephron segments using reverse transcription polymerase chain reaction.

Recent studies have revealed that arginine vasopressin (AVP) has at least two types of receptors in the kidney: V1a receptor and V2 receptor. In this study, microlocalization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in the glomerulus, initial cortical collecting duct, cortical collecting duct, outer medullary collecting duct, inner medullary collecting duct, and arcuate artery. Small but detectable signals were found in proximal convoluted and straight tubules, inner medullary thin limbs, and medullary thick ascending limbs. Large signals for V2 receptor mRNA were detected in the cortical collecting duct, outer medullary collecting duct, and inner medullary collecting duct. Small signals for V2 receptor were found in the inner medullary thick limbs, medullary thick ascending limbs, and initial cortical collecting duct. Next, we investigated V1a and V2 receptor mRNA regulation in the dehydrated state. During a 72-h water restriction state, the plasma AVP level increased and V2 receptor mRNA decreased in collecting ducts. In contrast, V1a receptor mRNA did not change significantly. Thus, the two AVP receptor subtypes are distributed differently along the nephron, and these mRNAs are regulated differently in the dehydrated state.

Animals↗

PubMed1993

Endothelin receptor subtypes are coupled to adenylate cyclase via different guanyl nucleotide-binding proteins in vasculature.

We have studied whether endothelin (ET) isopeptides have any effects on adenylate cyclase activity via different guanyl nucleotide-binding proteins (G-proteins) in cultured rat vascular smooth muscle cells (VSMC) and bovine endothelial cells (EC). Northern blot analysis clearly demonstrated gene expression of ETA receptors in VSMC and ETB receptors in EC. ET-1 dose-dependently (10(-9)-10(-6) M) stimulated cAMP formation in VSMC, whose effect was inhibited completely by ETA receptor antagonist (BQ-123) but not by indomethacin or quinacrine. The ET-1-induced cAMP formation was additive with isoproterenol but not with cholera toxin. In contrast, ET-3 and ETB receptor agonist (BQ-3020) dose-dependently (10(-9)-10(-6) M) inhibited forskolin-stimulated cAMP formation in EC, whose effect was completely abolished by pertussis toxin. Cholera toxin ADP ribosylated 45- and 52-kilodalton proteins in VSMC, whereas pertussis toxin ADP ribosylated the 41-kilodalton protein in EC. These data suggest that, in addition to phospholipase C via Gq, ETA and ETB receptor subtypes are functionally coupled to adenylate cyclase, possibly via Gs in VSMC and Gi in EC, respectively.

Adenylate Cyclase Toxin↗

PubMed1993

Cellular mechanism of natriuretic peptides-induced inhibition of endothelin-1 biosynthesis in rat endothelial cells.

We studied the cellular mechanism by which natriuretic peptides inhibit the synthesis and release of endothelin-1 (ET-1) in cultured rat aortic endothelial cells (EC). Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) showed dose-dependent and equipotent effects on displacement of [125I]ANP binding and generation of cGMP production in rat EC, whereas C-type natriuretic peptide and biologically inactive ANP analog had lesser effects. ANP and BNP as well as 8-bromo-cGMP had potent inhibitory effects on immunoreactive ET-1 release, the transient increase in the intracellular Ca2+ concentration, and the formation of inositol 1,4,5-trisphosphate stimulated by thrombin in rat EC. A cGMP-dependent protein kinase inhibitor (KT5823), but not a cAMP-dependent protein kinase inhibitor (KT5720), completely abolished the inhibitory effect of ANP on thrombin-induced immunoreactive Et-1 release. Northern blot analysis using cDNA for rat prepro-ET-1 as a probe showed that ANP and 8-bromo-cGMP, but not C-type natriuretic peptide, inhibited thrombin-induced prepro-ET-1 mRNA expression, whose effect was abolished by KT5823. These data suggest that ANP and BNP inhibit the thrombin-induced synthesis and release of ET-1 in cultured rat aortic EC by blocking phosphoinositide breakdown, possibly via natriuretic peptides type A receptor-mediated cGMP-dependent mechanism.

Animals↗

PubMed1993

Interleukin-1 beta induces nitric oxide production by a mouse pituitary tumour cell line (AtT20/D16).

To elucidate whether anterior pituitary cells express the nitric oxide (NO) synthase gene, we studied the synthesis of NO and the expression of NO synthase (NOS) mRNA by a mouse pituitary tumour cell line (AtT20/D16). Interleukin-1 beta (IL-1 beta) stimulated production of NO2-/NO3-(NOx) in a time-dependent manner and both NOx and cyclic GMP formation were stimulated in a dose-dependent manner by IL-1 beta. IL-1 beta-induced NOx production and intracellular cyclic GMP formation were similarly blocked by an NO synthase inhibitor, NG-monomethyl-L-arginine (LNMMA), whose effect was reversed by L-arginine, but not by D-arginine. Dexamethasone inhibited IL-1 beta-induced NOx production in a dose-dependent manner. A calmodulin inhibitor (W-7) showed no effect on IL-1 beta-induced NOx production, whereas cycloheximide and the actinomycin D completely inhibited NOx production. Northern blot analysis using cDNA for mouse macrophage-inducible NOS as a probe revealed the expression of inducible NOS mRNA in the cells only after exposure to IL-1 beta. Although IL-1 beta stimulated ACTH release from tumour cells, LNMMA failed to affect ACTH release stimulated by IL-1 beta. These results demonstrate for the first time that a pituitary tumour cell line (AtT20/D16) possesses cytokine-inducible and Ca2+/calmodulin-independent NOS, although NO may not be involved in ACTH release.

Amino Acid Oxidoreductases↗

PubMed1993

Effect of urodilatin on cGMP accumulation in the kidney.

Urodilatin is found in the urine and is thought to be produced in the kidney. The effect of urodilatin on cGMP accumulation in the kidney was investigated. cGMP accumulation by urodilatin and atrial natriuretic peptide (ANP) were compared with tubule suspensions from renal cortex, outer medulla, inner medulla, and microdissected nephron segments. Urodilatin-stimulated cGMP accumulation was higher in tubule suspensions from the inner medulla than in those from the cortex and outer medulla. The highest accumulation stimulated by 10(-6) M urodilatin among nephron segments was observed in glomeruli and inner medullary collecting ducts (IMCD). Small accumulations were seen in proximal convoluted tubules and medullary thick ascending limbs. Urodilatin-stimulated cGMP accumulation was almost equal to that stimulated by the same concentrations of ANP in these nephron segments. Urodilatin (10(-8) M) did not stimulate cGMP accumulation in glomeruli, but it stimulated cGMP accumulation in IMCD by threefold. This pattern was quite similar to that with ANP. It was concluded that urodilatin has a similar ability to ANP in stimulating cGMP synthesis and that the main target sites are glomeruli and IMCD.

Animals↗

PubMed1993

Mechanisms of regulatory volume increase in collecting duct cells.

To examine the mechanisms of cell volume regulation in response to hyperosmolality, segments of the inner stripe of rabbit outer medullary collecting duct (OMCDi) were perfused in vitro. The cross-sectional area of the tubule was monitored as an index of the relative cell volume. When luminal and basolateral osmolalities were increased from 290 to 390 mOsm simultaneously, the tubule cell shrank instantaneously and reswelled gradually, showing the so-called regulatory volume increase (RVI). Basolateral Na+ removal and addition of basolateral ethyl isopropyl amiloride (EIPA) decreased the RVI response by 76 and 66%, respectively. By contrast, apical Na+ removal had no effect on this response. RVI response was also inhibited by basolateral, but not luminal, Cl- removal (-63%), by total HCO3- removal (-74%), and by adding basolateral 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (-62%). Intracellular pH did not change significantly during RVI. Vasopressin increased RVI response by 56%. However, this increase was abolished in the absence of basolateral Na+ and Cl-, and in the presence of basolateral EIPA and DIDS. These results suggest that major mechanisms responsible for RVI are Na(+)-H+ and Cl(-)-HCO3- exchange systems in the basolateral membrane, and that these systems are stimulated by vasopressin in rabbit OMCDi.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1993

Rapid sequence variation of the hypervariable region of hepatitis C virus during the course of chronic infection.

To evaluate the clinical significance of sequence variations in the hypervariable region of hepatitis C virus during the course of chronic infection, we performed pairwise comparison of the predominant nucleotide sequences. Hepatitis C virus RNA was extracted from two plasma samples obtained from 12 chronically infected Japanese patients over approximately 1 yr. Complementary DNA containing the hypervariable region was amplified by means of reverse transcription-polymerase chain reaction and was directly sequenced for determination of predominant sequences. In all 12 individuals, the predominant sequence of the hypervariable region at the second time point differed from that at the first time point, and significant sequence variation was observed during this short period. A high proportion of these nucleotide substitutions (90%) resulted in changes of predicted amino acid sequences, indirect evidence of in vivo positive selection for these variants. There appeared to be an important difference in the rate of nucleotide sequence variation of the hypervariable region between four patients with flare-ups of their ALT levels (1.54 to 2.24 x 10(-1)/genome site/yr) and eight patients with quiescent courses (0.13 to 1.21 x 10(-1)/genome site/yr). These results demonstrate that rapid sequence variations of the hypervariable region of predominant virus population take place during the natural course of chronic hepatitis C virus infection. These sequence variations seem to occur as an adaptive response of hepatitis C virus to evade host immunity and may play a major role in the establishment of persistent infection and in the occasional flare-up of hepatitis.

Aged↗

PubMed1993

[Recent advances in vasopressin receptors and signal transduction system].

The antidiuretic hormone arginine vasopressin (AVP) receptors are G protein-coupled and have been divided into at least three types: V1a (vascular/hepatic) and V1b (anterior pituitary) receptors, which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+; and V2 (kidney) receptor, which is coupled to adenylate cyclase. Recently V1a and V2 receptor cDNAs were cloned. These cDNAs encode proteins with seven putative transmembrane domains and a similar structure to rhodopsin and other G protein-coupled receptors. Micro-localization of mRNA coding for V1a and V2 receptors was carried out in the rat kidney using a reverse transcription and polymerase chain reaction. Large signals for V1a receptor PCR product were detected in glomerulus, cortical collecting duct (CCD), outer medullary collecting duct (OMCD), inner medullary collecting duct (IMCD), and arcuate artery. Large signals for V2 receptor PCR product were detected in CCD, OMCD, and IMCD. 72-hour dehydration caused decrease of V2 receptor mRNA, but no change in V1a receptor mRNA in rat IMCD. These data show that mRNA coding for the two AVP receptor subtypes are distributed differently along the nephron and renal vascular system, and that these mRNAs are regulated differently in response to the dehydrated state. Recently, two reports of a mutation in the vasopressin V2 receptor gene in a kindred with X-rinked nephrogenic diabetes insipidus are published. These studies demonstrated that point mutation of V2 receptor gene causes the nephrogenic diabetes insipidus. Understanding the nature of defective diabetes insipidus may ultimately lead to improved therapy.

Animals↗

PubMed1993

[Assessment of the background count to measure the left ventricular ejection fraction with a nuclear stethoscope].

The nuclear stethoscope is a newly developed device for monitoring left ventricular ejection fraction (EF) with a pair of cadmium telluride detector for both left ventricular count (first channel) and background count (second channel). Although it is useful for evaluating the cardiac function during exercise, the methodology of the calculation for distinguishing the net ventricular blood count from the background count has not been established yet. In order to establish a reasonable method to calculate EF, we measured EF using a nuclear stethoscope and conventional gated blood pool scintigraphy in 20 healthy volunteers. All subjects underwent two supine ergometer exercise tests consisting of the 3 stages for the nuclear stethoscope and blood pool scintigraphy. The EF was determined with the following three method for the nuclear stethoscope; 1) Cut-off level was fixed at 70% of first channel, 2) Cut-off level at 75%, 3) Cut-off level was determined by the background count obtained from second channel. There was a poor relationship between the EFs obtained from gated blood scintigraphy and the EFs from the nuclear stethoscope calculated by any of these method. Regarding the EF calculated using the background count, however, the delta values of EF between rest and any of the 3 stages during exercise correlated closely to those EF from blood scintigraphy. When we apply the EF-at-rest value obtained from blood pool scintigraphy to analysis with the nuclear stethoscope, the EFs of 3 stages indicated good correlation (Stage I r = 0.91, Stage II r = 0.82, Stage III r = 0.69).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Therapeutic effect of hemodialysis on gouty arthritis and tophi in 2 patients with chronic renal failure].

Therapeutic effect of hemodialysis on gouty arthritis and tophi in 2 patients with chronic renal failure (CRF) is described. One patient was 74-year-old man with CRF due to benign nephrosclerosis, and had severe secondary gout. There were many tophi in metatarsophalangeal joints of the fingers and toes. Another patient was 44-year-old man with CRF probably due to familial gout. He had many tophi in elbows, knees, wrists, fingers and toes. In both cases initiation of hemodialysis treatment, at first temporally exacerbated gouty arthritis, but thereafter gradually eliminated the tophi. From these results, dialysis treatment is considered to be quite efficient method of treatment for gouty arthritis and tophi in patient with CRF. Gouty arthritis in CRF patient, which does not respond to the conservative therapy, should be considered to be one of the indices for commencement of hemodialysis.

Adult↗

PubMed1993

Adenosine deaminase isoenzymes in liver disease.

To clarify the clinical significance of increased serum adenosine deaminase (ADA) activity, and its mechanisms in various liver diseases, ADA isoenzyme activities (ADA1 and ADA2) in serum and the peripheral blood mononuclear cells were studied. High serum ADA activities were found in patients with acute hepatitis, alcoholic hepatic fibrosis, chronic active hepatitis, liver cirrhosis, and hepatoma. The ADA2:ADA ratio was decreased in acute hepatitis, but was increased in chronic active hepatitis and liver cirrhosis. Clinically, ADA2 activity was correlated with serum gamma-globulin levels. In chronic active hepatitis, total ADA activities in the peripheral blood mononuclear cells were similar to those in controls. Furthermore, ADA2 activities after phytohemagglutinin (PHA) stimulation were significantly lower than those without PHA stimulation, although total ADA activities were increased after PHA stimulation. These findings suggest that serum ADA isoenzyme activities may be a new marker for liver disease, and that the increased serum ADA2 in chronic active hepatitis is unlikely to be the result of an increase in ADA2 production by activated peripheral blood mononuclear cells.

Adenosine Deaminase↗