Biomedical subjects

R Kato

Publications and source records attributed to R Kato.

At least 307 records · Page 17Linked to original sources

PubMed1992

N-nitrosodialkylamine dealkylation in reconstituted systems containing cytochrome P-450 purified from phenobarbital- and beta-naphthoflavone-treated rats.

Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or beta-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl-benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N-nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians.

Animals↗

PubMed1992

Sex-specific cytochrome P450 as a cause of sex- and species-related differences in drug toxicity.

Male rats are the most frequently used experimental animals in drug toxicity tests. However, there are clear sex-related differences in toxicity of various drugs and chemicals in rats. These differences, in most cases, are closely connected with the sex-related differences in hepatic drug metabolisms. Recent studies indicate the existence of sex-specific cytochrome P450, such as P450-male (2C11) and P450-female (2C12) and P450(6) beta (3A2) in rat livers, and also show that their expression levels are markedly different between male and female rats. The expressions of sex-specific P450s are regulated by growth hormone, thyroid hormone, sex hormones and other chemicals. On the other hand, there are no or few cytochrome P450s that show the sex-related differences in species other than rats and mice. Although there are orthologous cytochrome P450s in viewpoints of amino acid sequence and substrate specificity in experimental animal species and humans, their expressions are not regulated by hormonal factors in most of the species. These differences may cause clear species differences, if male animals are used, in the toxicity caused by various drugs and chemicals. Thus we can predict the sex-related difference in drug toxicity on the basis of difference in the expression levels of sex-specific cytochrome P450s.

Animals↗

PubMed1992

Characterization of endogenous substrates for novel-type protein kinase C as well as conventional-type protein kinase C in primary cultured mouse epidermal cells.

In primary cultured mouse epidermal cells, phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC), induced changes in the phosphorylation levels of 10 proteins, termed KP-1 to -10, in two-dimensional PAGE. Seven of these proteins were phosphorylated and three were dephosphorylated. Similar changes were induced by other PKC activators, but not by inactive phorbol ester. Among these substrate proteins, phosphorylation of three proteins, i.e. KP-1 (pI 4.7/23,000 M(r)), KP-2 (pI 4.7/20,700 M(r)) and KP-10 (pI 4.7/25,500 M(r)) was markedly enhanced by PMA and inhibited by a potent PKC inhibitor staurosporine. In vitro phosphorylation studies and phosphoamino acid analysis, using these proteins as substrate and PKC preparations obtained from epidermal cell lysate, revealed that KP-1 and -2 were directly phosphorylated by Ca(2+)-, phospholipid-dependent protein kinase (conventional-type PKC; cPKC), but not by Ca(2+)-independent, phospholipid-dependent protein kinase (novel-type PKC; nPKC). On the other hand, KP-10 was mainly phosphorylated by nPKC in intact epidermal cells. These results indicate that cPKC and nPKC in epidermal cells have different substrate specificity for endogenous proteins and may induce different signal transduction.

Alkaloids↗

PubMed1992

Increases in NO2-/NO3- excretion in the urine as an indicator of the release of endothelium-derived relaxing factor during elevation of blood pressure.

1. Under hormonally constant conditions, the effects of a sudden increase in blood pressure on the release of endothelium-derived relaxing factor were evaluated by measuring urinary excretion of NO2-/NO3- in rats with renal denervation. 2. Elevation of blood pressure from 136 +/- 2 to 153 +/- 3 mmHg by an aortic clamp below the renal arteries induced a significant increase in urinary excretion of NO2-/NO3- from 76.6 +/- 4.2 x 10(2) to 108.1 +/- 8.3 x 10(2) pmol min-1 g-1 kidney weight (P less than 0.05). 3. Infusion of NG-monomethyl-L-arginine (1 mg min-1 kg-1) without an aortic clamp raised mean blood pressure to a similar level; however, urinary excretion of NO2-/NO3- was decreased significantly. 4. During infusion of NG-monomethyl-L-arginine, aortic occlusion caused a significant increase in blood pressure without any changes in NO2-/NO3- excretion in the urine. 5. These results suggest that the formation of NO, an indicator of endothelium-derived relaxing factor release, was increased by mechanical pressure elevation without apparent changes in hormonal and neural factors.

Animals↗

PubMed1992

Can the chest tube draining the pleural cavity with persistent air leakage be removed?

The pleural drain with persistent air leak in six selected patients after pulmonary surgery was clamped or removed without causing pulmonary collapse. In all the patients, air leak through the chest tube was present when speaking or coughing but not seen when breathing normally at rest or taking deep breaths. The fact that the chest tube could be removed in selected patients is explained by supposing the air leakage through an alveolopleural fistula is dependent on pressure difference between the alveoli and the pleural cavity, and this was confirmed in a rethoracotomy case for persistent air leak. Removal of the chest tube following the above-mentioned rationale would reduce the number of rethoracotomy cases for air leak and facilitate early removal of the chest tube in some patients.

Aged↗

PubMed1992

Differential sensitivities of transplacentally initiated newborn mouse epidermal cells to different tumor promoters.

Epidermal cells isolated from newborn mice and cultured in low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as monolayer. An increase in the medium Ca2+ concentration to normal level (1.8 mM) induced terminal differentiation of epidermal cells. Epidermal cells obtained from newborn mice transplacentally initiated with 7,12-dimethylbenz[a]anthracene (DMBA) produced a small number of rapidly growing cellular foci with epidermal morphology when the medium Ca2+ concentration was raised to normal level. The number of these Ca(2+)-induced differentiation-resistant colonies increased with increasing doses of DMBA, indicating that the differentiation-resistant colonies are the cells initiated by DMBA. Three differentiation-resistant colonies were cloned and designated as WY-1, WY-18 and WY-20 cells. All of these cell lines grew rapidly in the normal Ca2+ medium but not in the low Ca2+ medium. A potent skin tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), and other TPA-type second-stage tumor promoters such as mezerein and 12-O-retinoylphorbol-13-acetate, stimulated the growth of WY-18 and WY-20 cells in the low Ca2+ medium, but did not stimulate the growth of WY-1 cells. TPA stimulated DNA synthesis and ornithine decarboxylase induction in WY-18 and WY-20 cells but not in WY-1 cells. A non-TPA-type tumor promoter, okadaic acid, failed to stimulate the growth of these three cell lines. Another non-TPA-type tumor-promoting agent, 7-bromo-methylbenz[a]anthracene, also failed to stimulate the growth of WY-1 and WY-20 cells but stimulated the growth of WY-18 cells. WY-18 and WY-20 cells formed colonies in soft agar but WY-1 cells did not form colonies. When these cell lines were injected s.c. into nude mice, WY-1 cells produced fast-growing tumors, whereas WY-18 and WY-20 cells produced relatively slow-growing tumors. Our present results indicate that each initiated cell has different sensitivities for different types of tumor promoters, and each type of promoter acts on corresponding types of initiated cells.

Animals↗

PubMed1992

Staurosporine, a potent protein kinase C inhibitor, augments phorbol ester-caused ornithine decarboxylase induction in mouse epidermis.

A single topical application of 12-O-tetradecanoylphorbol-13-acetate (TPA) to mouse skin caused an induction of epidermal ornithine decarboxylase (ODC) activity. When mice were topically pretreated with staurosporine, a most potent protein kinase C inhibitor, 6-84 h prior to TPA treatment, TPA-caused ODC induction was markedly enhanced. The enhancement of TPA-caused ODC induction by staurosporine was most pronounced when the time interval between staurosporine and TPA treatment was 36 h. Staurosporine elicited this enhancing effect in a dose-related manner. Staurosporine by itself also induced epidermal ODC activity. But the activity induced was very slight and would not directly contribute to the enhancing effect of this compound. Although staurosporine markedly augmented TPA-caused ODC induction, staurosporine-caused ODC induction was not augmented by this compound. Other protein kinase C inhibitors, such as 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, sphingosine and palmitoylcarnitine did not mimic the enhancing effect of staurosporine. These results indicate that the enhancement of ODC induction by staurosporine is specific for the induction caused by TPA and that this enhancing effect is not related to the protein kinase C inhibitory action of staurosporine. TPA-caused epidermal ODC induction was inhibited by indomethacin, and this inhibition was reversed by prostaglandin E2 (PGE2). Staurosporine-caused ODC induction was also inhibited by indomethacin but the inhibition was not reversed by PGE2, indicating that the mechanism of staurosporine-caused ODC induction is different from that of TPA.

Administration, Topical↗

PubMed1992

Involvement of prostaglandin E2 in ornithine decarboxylase induction by a tumor-promoting agent, 7-bromomethylbenz[a]anthracene, in mouse epidermis.

A single topical application of 7-bromomethyl-benz[a]anthracene (BrMBA; 200 nmol) to mouse skin induced epidermal ornithine decarboxylase (ODC) activity. A topical application of indomethacin (1.2 mumol), a cyclooxygenase inhibitor, 10 min before BrMBA application markedly inhibited BrMBA-caused ODC induction. Concurrent application of prostaglandin E2 (PGE2; 0.1-1.5 mumol) reversed the inhibitory effect of indomethacin. Without indomethacin, PGE2 suppressed BrMBA-caused ODC induction. The results indicate that PGE2 has dual actions on the BrMBA-caused ODC induction, i.e. PGE2 plays an essential role in ODC induction caused by BrMBA, whereas exogenous PGE2 rather suppressed BrMBA-caused ODC induction.

Animals↗

PubMed1992

Phenotypic expression of carcinogen-initiated epidermal cells to tumor cells by 12-O-tetradecanoylphorbol-13-acetate in a manner dependent on 3T3 fibroblast-derived humoral factor(s).

Primary cultured newborn mouse epidermal cells cultured in the low Ca2+ (0.02 mM) medium showed typical basal cell morphology and proliferated as a monolayer. A stepwise increase in medium Ca2+ concentration induced terminal differentiation of epidermal cells. In the case of epidermal cells obtained from newborn mice transplacentally initiated with 7,12-dimethylbenz[a]anthracene (DMBA) or epidermal cells initiated in vitro by DMBA, a small number of rapidly growing cellular foci with epidermal morphology appeared and proliferated when the medium Ca2+ concentration was raised. Without increasing Ca2+ concentration, such foci never appeared. However, the Ca2+ concentration of the extracellular milieu of basal epidermal cells is known to be very low in in vivo epidermis. Under the low Ca2+ conditions, 12-O-tetradecanoylphorbol-13-acetate (TPA), a most potent skin tumor promoter, never induced rapidly growing cellular foci. When the initiated epidermal cells were co-cultured with 3T3 fibroblasts but without direct cell-to-cell contact, TPA induced rapidly growing cellular foci even under the low Ca2+ condition. Without initiation, such cellular foci hardly appeared. 3T3 fibroblasts induced only a very small number of cellular foci in the absence of TPA. Co-culture with mouse peritoneal macrophages was not effective in inducing such cellular foci, indicating that the effect is 3T3 fibroblast specific. The conditioned medium of 3T3 fibroblasts was also capable of inducing such cellular foci. Three of these rapidly growing cellular foci were cloned and designated as WYF-30, WYF-31 and WYF-32 respectively. All of these three cell lines grew rapidly in the normal (1.8 mM) Ca2+ medium, indicating that these cell lines were resistant to Ca(2+)-induced differentiation. In the low Ca2+ medium, the growth of these three cell lines was stimulated by TPA. All three cell lines formed colonies in soft agar. The number of colonies formed under the normal Ca2+ condition was larger than that formed under the low Ca2+ condition. Under the low Ca2+ condition, the colony formation of each cell line was augmented by TPA. All the cell lines formed tumors in nude mice. These results indicate that TPA induces phenotypic expression of dormant initiated cells to tumor cells in a manner dependent on 3T3 fibroblast-derived humoral factor(s).

3T3 Cells↗

PubMed1992

Sulfotransferase-mediated DNA binding of N-hydroxyarylamines(amide) in liver cytosols from human and experimental animals.

Characteristics of cytosolic sulfotransferase-mediated binding of carcinogenic N-hydroxyarylamines(amide) have been investigated and compared among experimental animal species and humans in vitro. Human cytosols exhibited significant sulfating activities towards 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), N-hydroxy-2-aminofluorene (N-hydroxy-AAF) and N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), but had no detectable activity toward 2-hydroxyamino-3-methyl-imidazo[4,5-f]quinoline (N-hydroxy-IQ). Although the extent of the covalent binding of these N-hydroxyarylamines(amide) differed significantly among individuals, clear correlations were observed among the sulfation of N-hydroxyarylamines (amide) and also with p-nitrophenol sulfation. Hepatic cytosols from mouse, rat, guinea-pig, hamster, rabbit, dog and monkey also mediated the binding of N-hydroxy-Glu-P-1, N-hydroxy-AF and N-hydroxy-AAF, while only rat cytosols showed detectable DNA binding of N-hydroxy-IQ. Among the species examined, rat showed the highest capability for activating these N-hydroxyarylamines(amides). Significant sex-related differences were detected in rat, dog and monkey for all substrates examined, except N-hydroxy-IQ. Clear correlations were observed in the animal species between N-hydroxyarylamines(amide), but not with p-nitrophenol. Using an ion-exchange chromatographic system, sulfating activity of p-nitrophenol in human livers was separated into two fractions and the PAPS-dependent DNA binding of N-hydroxy-AF was supported mainly by the later fraction. On Western blots, an immunoreactive protein was detected in these fractions using an antibody raised against rat hepatic N-hydroxy-AAF sulfotransferase. The band was also detected in human hepatic cytosols with considerable individual variation in their amounts. These results indicate the involvement of a closely related form(s) of sulfotransferase in the PAPS-mediated activation of N-hydroxyarylamines(amide) in human as well as in the experimental animal species.

Animals↗

PubMed1992

Hepatic triiodothyronine sulfation and its regulation by growth hormone and triiodothyronine in rats.

The regulatory mechanism of cytosolic sulfation of T3 has been studied in rat liver. Sulfation of T3 is sexually differentiated in adult rats of Sprague-Dawley (SD), Fisher 344, and ACI strains. In SD strain, the male animals showed 4 times higher sulfating activity than did the females. The specific activity was decreased by hypophysectomy of male adult rats, but was not affected in the females. Thus, the sex-difference was abolished in the hypophysectomized condition. Supplement of human GH intermittently twice daily for 7 days, to mimic the male secretory pattern, increased T3 sulfating activity in both sexes of hypophysectomized rats, whereas continuous infusion to mimic a female secretory pattern had no appreciable effect. Cytosolic sulfation of T3 was decreased by 25 to 30% by thyroidectomy or propylthiouracil treatment of male adult rats, and was restored by the supplementation of T3 (50 micrograms/kg daily for 7 days) to thyroidectomized rats. Administration of T3 in hypophysectomized rats almost completely restored the sulfating activity in the males and increased the activity in the females. Cytosolic T3 sulfation was inhibited by the addition of known inhibitors of phenol sulfotransferase, pentachlorophenol or 2,6-dichloro-4-nitrophenol. These results indicate a role of pituitary GH in hepatic sulfation of thyroid hormones in rats. The data obtained also raise the possibility that GH may modify the effect of thyroid hormones on the pituitary by a feed-back mechanism through changing the level of a sex-dominant phenol sulfotransferase(s) in rat livers. T3 was also sulfated in hepatic cytosols of mouse, hamster, rabbit, dog, monkey, and human.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

New method of investigating functional roles of pressure-sensitive mechanoreceptor in human endothelial cells.

The role of pressure-sensitive mechanoreceptors (PSMRs) in histamine-stimulated nitric oxide release from cultured human endothelial cells was investigated, using our new method (helium pack method). PSMRs were stimulated by various levels of pressure applied in addition to atmospheric pressure (40, 80, 120, and 160 mm Hg). Histamine-stimulated nitric oxide release was inhibited in a pressure-dependent manner. Our results suggest that PSMRs modulate nitric oxide release from endothelial cells.

Cells, Cultured↗

PubMed1992

L-arginine as an antihypertensive agent.

L-Arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), was administered intravenously in five patients with essential hypertension, one with renovascular hypertension, one with primary aldosteronism, and one with Cushing's syndrome. During the administration, the mean arterial pressure decreased concomitantly with an elevation of cardiac output and a fall in total peripheral resistance in all cases. Indicators of NO release in vivo such as plasma concentrations of L-citrulline and urinary excretion of nitrite/nitrate increased simultaneously during the administration. These results suggest that exogenous L-arginine can produce a vasodilatory effect via stimulating NO release in hypertensives.

Antihypertensive Agents↗

PubMed1992

Stimulus-induced accumulation of inositol tetrakis-, pentakis-, and hexakisphosphates in N1E-115 neuroblastoma cells.

When [3H]inositol-prelabelled N1E-115 cells were stimulated with carbamylcholine (CCh) (100 microM), high K+ (60 mM), and prostaglandin E1 (PGE1) (10 microM), a transient increase in [3H]inositol pentakisphosphate (InsP5) accumulation was observed. The accumulation reached its maximum level at 15 s and had declined to the basal level at 2 min. CCh, high K+, and PGE1 also caused accumulations of [3H]inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], [3H]inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4], and [3H]inositol hexakisphosphate (InsP6). Muscarine and CCh induced accumulations of [3H]Ins(1,4,5)P3, [3H]-Ins(1,3,4,6)P4, [3H]InsP5, and [3H]InsP6 with a similar potency and exerted these maximal effects at 100 microM, whereas nicotine failed to do so at 1 mM. With a slower time course, CCh, high K+, and PGE1 caused accumulations of [3H]-inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] and [3H]inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4]. In an N1E-115 cell homogenate, [3H]Ins(1,4,5)P3, [3H]Ins(1,3,4,5)P4, and [3H]Ins(1,3,4)P3 were converted to [3H]InsP5 through [3H]-Ins(1,3,4,6)P4. The above results indicate that Ins(1,3,4,6)P4, InsP5, and InsP6 are rapidly formed by several kinds of stimulants in N1E-115 cells.

Alprostadil↗

PubMed1992

Anthralin, a non-TPA type tumor promoter, synergistically enhances phorbol ester-caused prostaglandin E2 release from primary cultured mouse epidermal cells.

Primary cultures of mouse epidermal cells (i.e., target cells of skin tumor promotion) stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) release prostaglandin E2 within 30 min. Anthralin, a non-TPA type tumor promoter, also stimulated PGE2 release; however, no release was detectable at least up to 4 hr after the addition of anthralin. When the cells were incubated with TPA plus anthralin, both PGE2 and arachidonic acid release were synergistically enhanced. Other non-TPA type tumor promoters, i.e., chrysarobin, 7-bromomethylbenz[a]anthracene, benzoylperoxide, okadaic acid and palytoxin, did not potentiate the TPA-caused PGE2 release. In protein kinase C-down regulated cells, the synergistic stimulation of PGE2 and arachidonic acid release by TPA plus anthralin were not detected. Anthralin plus TPA did not alter the incorporation of arachidonic acid into cellular phospholipids. Cellular cyclooxygenase activity was increased 2 hr after TPA stimulation. Anthralin-caused increase in cyclooxygenase activity was detected at 6 hr after the addition of anthralin. Cyclooxygenase activity was synergistically increased by treating the cells with TPA plus anthralin. Cycloheximide and actinomycin D inhibited the increase in cyclooxygenase activity caused by anthralin or TPA plus anthralin. These results indicate that anthralin synergistically stimulates TPA-caused PGE2 release by synergistically increasing arachidonic acid release and cellular cyclooxygenase activity.

Animals↗

PubMed1992

Prediction of the outcome of postoperative hypocalcemia in Graves' disease.

Symptomatic hypocalcemia sometimes follows subtotal thyroidectomy for Graves' disease. Irreversible damage to the parathyroids contributes to permanent hypocalcemia and the mechanism for a transient hypocalcemia is thought to be different from that of a permanent one. However, sensitive assays for parathyroid hormones (PTH), which had recently become available, revealed that levels of PTH decrease in patients with transient hypocalcemia. In order to differentiate a prolonged hypocalcemia from a transient one, calcium and inorganic phosphate concentrations in serum as well as in urine, and whole molecule-PTH levels were determined in 18 Graves' disease patients with postoperative hypocalcemia just after the initial symptoms for hypocalcemia appeared. In 13 patients, medication was withdrawn within one month since serum calcium levels had returned to normal (transient hypocalcemia). In five other patients, medication was required for six months or more to maintain normocalcemia (prolonged hypocalcemia). The same parameters were determined after surgery in eight Graves' disease patients without hypocalcemia. Urinary inorganic phosphate concentrations in patients with prolonged hypocalcemia (0.02 +/- 0.01 mmol/mmol Cr) were significantly lower (P less than 0.01) than those in patients with transient hypocalcemia (1.59 +/- 1.59 mmol/mmol Cr) or those in control patients (1.27 +/- 0.70 mmol/mmol Cr). Preoperative concentrations of calcium and inorganic phosphate in serum and urine, and serum alkaline-phosphatase activities were also determined. However, there were no significant differences in these parameters between patients with prolonged and those with transient hypocalcemia. It is concluded that prolonged hypocalcemia is discriminated from the transient type by determining the urinary inorganic phosphate at the time of appearance of the initial symptoms for hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1992

Effect of systemic L-arginine administration on hemodynamics and nitric oxide release in man.

The effects of L-arginine administration on systemic hemodynamics and plasma concentrations of neuro-endocrine hormones and amino acids were investigated in 10 normotensive healthy volunteers. Nitrite/nitrate in urine and cyclic guanosine monophosphate (c-GMP) in plasma were also measured as indicators of release of nitric oxide (NO). L-arginine administration (30 g/300 ml/30 min) caused hypotension (mean arterial pressure; 79.3 +/- 3.9 mmHg fell to 68.8 +/- 2.2 mmHg) with tachycardia (62.3 +/- 2.3 beats/min increased to 67.5 +/- 1.9 beats/min). The plasma concentration of L-arginine before administration was 98.8 +/- 8.2 mumol/l and increased to 7263 +/- 567 mumol/l 20 min after administration. Cardiac output also increased to 127.2 +/- 3.9% by L-arginine administration. Total peripheral resistance was calculated to fall to 65.9 +/- 2.0%. L-arginine administration slightly changed several hormones, but all values were within normal ranges. Nitrite/nitrate in urine increased 142.1 +/- 12.4% compared to the values before L-arginine administration. Plasma concentrations of c-GMP and L-citrulline, the by-product of NO from L-arginine, were also significantly increased by L-arginine administration. All our results provide evidence for the first time that systemically administered L-arginine releases NO in man.

Adult↗

PubMed1992

Ticlopidine treatment in idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia accompanied by nephrotic syndrome.

A 36-year-old woman was admitted for idiopathic plasmacytic lymphadenopathy with polyclonal hyperimmunoglobulinemia (IPL) associated with nephrotic syndrome. She was expected to lapse into renal failure because renal biopsy showed focal glomerulosclerosis. VEMP chemotherapy and bolus methyl prednisolone were not effective against excessive urine protein of over 10 g/day. We thus began administration of ticlopidine (6 mg/kg/day), prednisolone (0.4 mg/kg/day) and cyclophosphamide (1 mg/kg/day). After 3 months of this regimen, the urine protein level decreased to less than 0.5 g/day, and renal function was maintained for more than 3 years. It is suggested that ticlopidine is effective for nephropathy complications associated with IPL.

Adult↗