Biomedical subjects

I Amano

Publications and source records attributed to I Amano.

At least 19 recordsLinked to original sources

PubMed1999

[Successful lithium carbonate therapy for a patient with intractable and severe aplastic anemia].

A 16-year-old female patient who had been given a diagnosis of severe aplastic anemia underwent 2 courses of a combined regimen of corticosteroid pulse therapy and androgen therapy. This proved ineffective. Antilymphocyte globulin therapy was also ineffective. The patient was then given lithium carbonate at a dose of 600 mg/day in combination with an androgen derivative. This had a dramatic effect on her peripheral blood smear. Within 3 weeks after the first course of this treatment, she no longer required red blood cell transfusions. Also, once the lithium carbonate dose was increased to 1,200 mg/day, the patient no longer needed exogenous platelet transfusions. Approximately 6 months after the start of combination therapy, a peripheral blood smear showed entirely normal results. However, 2 months after lithium carbonate was discontinued probably as a result of drug-induced liver dysfunction, both leukocytopenia and thrombocytopenia reappeared. Therefore, lithium carbonate was readministered at a dose of 400 mg/day, and later at a dose of 800 mg/day. Again, the patient showed improvements in 3 blood components without any adverse effects. We concluded that lithium therapy was remarkably useful for this patient with intractable and severe aplastic anemia.

Adolescent↗

PubMed1998

Effects of L-carnitine supplementation on muscular symptoms in hemodialyzed patients.

Various muscle symptoms are well recognized among patients on maintenance hemodialysis. Carnitine deficiency may be an important factor of dialysis-associated muscle symptoms, whereas high-dose L-carnitine supplementation may result in unphysiologically high plasma levels of carnitine and carnitine esters. We studied the effect of low-dose L-carnitine treatment (500 mg/d) on muscle symptoms, plasma carnitine fractions, and lipid profiles in 30 periodically dialyzed patients with muscular weakness, fatigue, or cramps/aches. After 12 weeks of L-carnitine treatment, about two-thirds of patients had at least some improvement in muscular symptoms, whereas carnitine fractions were normal or slightly above normal ranges, but lipid profiles showed no demonstrable changes. This study also showed the correlation between plasma-free carnitine deficiency and months on dialysis. These results suggest that prolonged low-dose L-carnitine treatment can improve dialysis-associated muscle symptoms by restoring carnitine tissue levels and washing out acyl moieties.

Administration, Oral↗

PubMed1998

Peripheral deletion of gammadelta T cells in haemodialysis patients.

Many patients with end-stage renal disease have altered host defenses against infectious agents. We have demonstrated that T cells, which play an important role in the immunological response, may undergo apoptosis by the Fas system in uraemia. To elucidate whether gammadelta T cells, which function as a first defense against intracellular pathogens, are altered in number or characteristics in dialysis patients, surface expressions of TCR, LFA-1 and Fas antigen on peripheral T cells were examined by immunofluorescence analysis. We demonstrated that the proportions of peripheral gammadelta T cells are altered significantly in haemodialysis (HD) patients. Interestingly, there were marked differences in the levels of expression of LFA-1 and Fas antigen between the two types of T cells. Moreover, both the expression of LFA-1 and that of Fas antigen were enhanced significantly in HD patients compared with normal controls. These results suggest that circulating gammadelta T cells may be susceptible to activation-induced cell death in comparison with alphabeta T cells in uraemic environments.

Adult↗

PubMed1998

Increased serum midkine levels during hemodialysis using heparin in chronic renal failure.

The heparin-binding growth factor midkine (MK) has been implicated in neuron growth, angiogenesis, and inflammation. In this study, to elucidate the involvement of MK in the development of pathologies associated with uremia, we examined the serum MK levels in patients receiving hemodialysis (HD) by a highly sensitive enzyme-linked immunoassay. Although no significant difference was found between control serum and serum before dialysis in HD patients, serum MK levels increased significantly at the early stage of HD sessions using heparin and gradually decreased after dialysis. In normal controls, intravenous administration of heparin induced a similar sudden increase of MK, but the subsequent decrease was also rapid. In an in vitro study, MK was released in time- and heparin-dose dependent manner from cultured vessels, but not from peripheral leukocytes. These results indicate that, in HD patients, MK is released mainly from endothelial cells immediately after administration of heparin during HD and disappears gradually from blood due to renal impairment. This phenomenon might affect some complications associated with HD.

Adult↗

PubMed1997

[Apoptosis in uremic complication].

Chronic renal failure (CRF) is often complicated by lymphopenia and sometimes by hepatic dysfunction. To elucidate the involvement of apoptosis in these complications, we analyzed Fas antigen which mediates apoptosis on peripheral blood T cells and hepatic cells. T cells from uremic patients expressed Fas with higher intensity than control T cells. When cultured in vitro, uremic T cells were shown to undergo acceleratd apoptosis in correlation with Fas expression. Immunohistological analysis of liver tissues revealed that hepatocytes in patients both with chronic hepatitis and with CRF expressed higher levels of Fas than those in patients alone with chronic hepatitis. These results suggest that T cells and hepatocytes in CRF may undergo apoptosis by the Fas system.

Apoptosis↗

PubMed1996

Regulation of phosphorylation of Gi2 alpha protein controls the secretory response to isoproterenol in rat parotid tissues.

Treatment of rat parotid tissues with 1 microM isoproterenol (IPR) for 10 min caused a 60% decrease in pertussis toxin (IAP)-catalyzed ADP-ribosylation of Gi alpha and resulted in supersensitivity of amylase secretion from the tissues. However, conversely, IPR treatment for 30 min caused a 40% increase in IAP-catalyzed ADP-ribosylation of Gi alpha, coupled with desensitization of amylase secretion. No changes in Gs function were observed in IPR-induced phenomena. Pretreatment with okadaic acid induced enhancement of the supersensitivity of amylase secretion and disappearance of the desensitization. These phenomena were accompanied with decreases in IAP-catalyzed ADP-ribosylation of Gi alpha. IPR treatment for 30 min caused a 50% decrease in phosphorylation of Gi2 alpha immunoprecipitated with anti-G protein antiserum (AS/7) from [32P]Pi-labeled cells, but such treatment for 10 min caused a 40% increase in phosphorylation in the cells pretreated with okadaic acid. Phosphorylation and dephosphorylation of immunoprecipitates with AS/7 by protein kinase A (PKA) and alkaline phosphatase caused decreases and increases in IAP-catalyzed ADP-ribosylation, respectively, indicating the presence of PKA-mediated phosphorylation sites on Gi2 alpha. Thus, the control of the phosphorylation of Gi2 alpha is of importance and relevance in the regulation of biological processes and cellular responses.

Adenosine Diphosphate Ribose↗

PubMed1996

First evidence for accumulation of protein-bound and protein-free pyrraline in human uremic plasma by mass spectrometry.

Glucose-derived advanced glycation end products (AGEs) cross-link proteins and cause various biological tissue damage. One of them, pyrraline [epsilon-2-(formyl-5-hydroxymethyl-pyrrol-1-yl) -L-norleucine], has been demonstrated by utilizing antibody to accumulate in plasma and sclerosed matrix of diabetic individuals, suggesting responsibility for diabetic complications. To elucidate the involvement of pyrraline in uremia, we examined the pyrraline levels in patients with chronic renal failure by a mass spectrometric approach. Here we show that protein-free pyrraline as well as pyrraline with binding protein are significantly increased in non-diabetic uremic plasma compared to healthy subjects. Our results suggest that circulating pyrraline could be a substance contributing to complications in uremia.

Blood Proteins↗

PubMed1995

Relationship between susceptibility to apoptosis and Fas expression in peripheral blood T cells from uremic patients: a possible mechanism for lymphopenia in chronic renal failure.

Chronic renal failure (CRF) is often complicated by lymphopenia, which may be partly responsible for immune deficiency. We hypothesized that lymphopenia in CRF might result from apoptosis of T cells in vivo. To elucidate the involvement of Fas antigen which mediates apoptosis, we analyzed Fas expression on peripheral blood T cells in uremic non-dialyzed (non-HD) patients and hemodialysis (HD) patients. T cells from both uremic groups expressed Fas with higher intensity than control T cells. When two uremic groups were compared, Fas intensity on T cells was significantly higher in non-HD patients than in patients on HD. Moreover, uremic T cells were shown to undergo accelerated apoptosis when cultured in vitro, in correlation with Fas expression. Our results suggest that T cells in CRF may undergo apoptosis by the Fas system and that hemodialysis treatment has beneficial effects in the light of the inhibition of T cell apoptosis.

Apoptosis↗

PubMed1995

Age-dependent changes in response of rat prostatic tissues to isoproterenol and forskolin: changes with sexual maturation in function of G proteins.

Developmental changes in the responses of rat ventral prostate to isoproterenol (IPR) and forskolin (F) were studied in relation to the function of beta-adrenoceptor-adenylate cyclase system. The response of adenylate cyclase in the tissues to IPR at 10(-7)M and above was steadily enhanced after birth and reached a maximum at 12 weeks, followed by a decrease with age. In contrast, the response of the enzyme to F at 10(-7)M and above was highest at 2 weeks, but thereafter decreased. The changes in the response of the enzyme to IPR coincided with changes in the beta-adrenoceptor density and the binding ability of GTP binding proteins (G proteins) to GTP. The ADP-ribosylation of inhibitory G proteins (Gi proteins) catalyzed by pertussis toxin (IAP) decreased 70% in the tissues from 4 to 8 weeks, and then maintained this level. On the other hand, the ADP-ribosylation of stimulatory G proteins (Gs proteins) catalyzed by cholera toxin (CT) increased only 20% in the tissues from 2 to 4 weeks. Thus, the ratio of ADP-ribosylation of Gs to that of Gi significantly increased from 4 weeks, reaching a maximum at 12 weeks, but thereafter decreased gradually with age. These changes paralleled those in the function of G proteins and the response of the enzyme to IPR. It is suggested that the rapid and marked decrease in apparent level of Gi proteins in the rat ventral prostate after 4 weeks may have a key role in controlling the function of the beta-adrenoceptor-adenylate cyclase system in the tissues.

Adenosine Diphosphate Ribose↗

PubMed1995

Mechanism of isoproterenol-induced heterologous desensitization of mucin secretion from rat submandibular glands. Regulation of phosphorylation of Gi proteins controls the cell response to the subsequent stimulation.

Short-term treatment of rat submandibular tissues with 10 microM isoproterenol (IPR) resulted in reduction of mucin secretion in response to the agonist during further incubation, and in increases in EC50 values. This IPR-induced reduction of secretion was coupled with selective decreases in the number of beta-adrenoceptors in the tissues and in their affinity for agonists, as assessed by measurement of the specific binding of [3H]dihydroalprenolol. Treatment of the tissues with IPR caused a 30% decrease in IPR-stimulated adenylate cyclase activity and a 25% increase in the GTP binding capacity of inhibitory G proteins (Gi proteins). This IPR treatment triggered a 60% increase in the ability of pertussis toxin (IAP) to catalyze ADP-ribosylation of Gi proteins in the tissue membranes. Enhanced function of stimulatory G proteins (Gs proteins) was observed only during the first incubation of the tissues with IPR. The IAP-catalyzed ADP-ribosylation of Gi proteins in tissues treated with IPR was decreased by prior treatment with cyclic AMP dependent protein kinase, but was increased markedly by prior treatment with alkaline phosphatase. Neither IPR-induced desensitization of protein secretion nor increase in the IAP-catalyzed ADP-ribosylation of Gi proteins was observed in the tissues pretreated with 0.25 microM okadaic acid. These findings suggest that the regulation of Gi protein phosphorylation plays an important role in the IPR-induced heterologous desensitization of mucin secretion from rat submandibular glands.

Adrenergic beta-Agonists↗

PubMed1994

Dephosphorylation of nuclear non-histone proteins in submandibular glands of rats treated with isoproterenol.

Protein phosphatase that removed [32P]phosphate from non-histone proteins, i.e., phenol-soluble acidic proteins, more rapidly and strongly than from histone proteins was present in nuclei of rat submandibular glands, but was not associated with chromatin. Cyclic AMP (10(-4)-10(-2) mM) stimulated the dephosphorylation of non-histone proteins, but not that of histone proteins. After a single injection of isoproterenol (IPR), the dephosphorylation of non-histone proteins in rat submandibular gland nuclei increased within 15 min, reached a maximum in 30 min and returned to normal control levels within 4 h. The stimulation of dephosphorylation of non-histone proteins induced by IPR was not observed after prior treatment of the animals with dichloroisoproterenol. The dephosphorylation of histone proteins was not affected by the injection of IPR. Stimulation of beta-adrenoceptors with IPR in rat submandibular glands resulted in increase in cyclic AMP and decrease in RNA synthesis in the tissues in the first few hours after the injection. This decrease in RNA synthesis was temporary and was preceded by the increase in cyclic AMP level and in the dephosphorylation of non-histone acidic proteins in the tissues. These results suggest that protein phosphatase in nuclei plays an important part in the events controlling RNA synthesis by regulating the state of phosphorylation of non-histone acidic proteins. In addition, the phosphatase may be regulated by a function of the cytoplasmic membranes.

Animals↗

PubMed1993

Age-dependent changes in the phosphorylation of nuclear proteins of submandibular glands in isoproterenol-treated rats.

Age-dependent changes in the regulation of the phosphorylation of nuclear proteins were investigated in relation to DNA synthesis in rat submandibular glands after injection of isoproterenol (IPR). The level of phosphorylation of nuclear proteins in the tissue increased rapidly after birth, reaching a maximum at 4 weeks, and then decreased to the level of 52-week-old rats. The level of protein kinase activity in nuclei varied in parallel with that of phosphorylation of nuclear non-histone proteins after birth. The time after the injection of IPR required to initiate the phosphorylation of nuclear non-histone proteins of rat submandibular glands, which occurs prior to the onset of RNA synthesis that precedes the replication of DNA, increased with age. These results suggest that this delayed onset of phosphorylation plays a regulatory role in cell proliferation and cell function during aging.

Aging↗

PubMed1993

[Accumulation of a disopyramide metabolite in renal failure].

Twenty-nine cases of hypoglycemia induced by disopyramide (DP) have been reported in the literature to date. Twenty of the reported cases showed hypo-renal function and a high concentration was rare. DP is metabolized to mono-N-dealkyldisopyramide (MND) in the liver and accumulation of MND is to be expected in renal failure. Both DP and MND bind mainly to alpha-1-acid glycoprotein (AAG) in the plasma. In 10 hemodialysis (HD) patients with normal liver function receiving DP therapy in the steady state. DP, MND and AAG were measured pre- and post-HD. Ten patients with normal renal and liver function were selected as the controls. The DP concentration was 2.08 +/- 0.39 micrograms/ml (mean +/- SD) in the control group, and the pre- and post-HD levels were 2.40 +/- 1.08 micrograms/ml and 1.73 +/- 0.87 micrograms/ml, respectively, in the HD group. The MND concentration was 0.42 +/- 0.23 micrograms/ml in the controls, 1.53 +/- 0.52 micrograms/ml in pre-HD and 1.08 +/- 0.32 micrograms/ml in post-HD. Although DP and MND are both classified as substances of small molecular weight, the average decrease in plasma concentration from pre- to post-HD was under 30% with both agents. The MND/DP ratio in the HD group was higher than in the controls, but there was no significant difference between pre- and post-HD. The AAG level was 75 +/- 5mg/dl in the controls and 109 +/- 11mg/dl before HD in the HD group (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Diurnal variation of amylase secretion is coupled with alterations of beta-adrenoceptors in the rat parotid gland.

Diurnal changes in the neurotransmitter receptors are important for studying the receptor function in neurophysiology. The purpose of this study is to gain an insight into the regulatory mechanisms of the diurnal variation of amylase secretion. Rat salivary amylase levels showed a diurnal variation with two peaks, a marked peak at 13 h and a lesser peak at 21 h. This increase in salivary amylase levels was completely inhibited by pretreatment of rats with the beta-adrenergic antagonist propranolol, but not by the alpha-adrenergic antagonist phentolamine. Amylase level in parotid tissue homogenate also showed a diurnal change, but there was only one peak, at 13 h. The number of maximal binding sites (Bmax) for [3H]dihydroalprenolol (DHA) in parotid membranes showed a diurnal variation with two marked peaks at 13 and 21 h, but the affinity of parotid beta-adrenoceptors for agonists or antagonists did not show any diurnal changes. Phosphorylation of nuclear non-histone proteins in the rat parotid gland showed diurnal variation with two marked peaks at 13 and 21 h. These results indicate that a diurnal variation in the number of rat parotid beta-adrenoceptors, which is presumably regulated by gene expression, is coupled with a change in salivary amylase secretion.

Amylases↗

PubMed1992