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Biomedical subjects

H Kai

Publications and source records attributed to H Kai.

At least 19 recordsLinked to original sources
PubMed2001

Up-regulation by clarithromycin of alpha(1)-acid glycoprotein expression in liver and primary cultured hepatocytes.

alpha(1)-Acid glycoprotein (AGP) is the major transport protein for cationic drugs, endogenous ligands, and some anionic drugs in plasma. Hepatic synthesis and secretion of AGP are altered during acute inflammation as well as by a number of drugs. This alteration could influence the binding of drugs and its biological function. Macrolide antibiotics are widely used in the treatment of a variety of infectious diseases. The effects of macrolide antibiotics have been studied with respect to rat AGP expression in vivo. After the individual administration of six macrolides to rats, with the exception of oleandomycin, five increased AGP levels in serum. Of these five, clarithromycin (CAM) was the most potent inducer of AGP, which reached a maximum level between 3 to 7 days after administration. CAM increased the steady-state level of AGP mRNA in liver as well as protein level in serum in a dose-dependent manner. In addition, CAM increased AGP mRNA levels in primary cultured hepatocytes. In the luciferase promoter assay, CAM potentiated dexamethasone-increased promoter activity of the AGP gene, which contained the glucocorticoid response element, in cultured rat hepatocytes, although CAM itself had no effect on its activity. The effect of CAM and dexamethasone was diminished by glucocorticoid response element deletion or mutation or by adding the antiglucocorticoid, RU486. Further, in the mouse mammary tumor virus (MMTV) promoter containing functional glucocorticoid response element, CAM potentiated dexamethasone-increased promoter activity. In the adrenalectomized rats, CAM did not increase AGP levels in serum. These findings suggest that CAM may cause transcriptional induction of AGP, at least in part, via a glucocorticoid-mediated mechanism.

5' Untranslated Regions↗
PubMed2001

Anti-influenza virus activities of 2-alkoxyimino-n-(2-isoxazolin-3-ylmethyl)acetamides.

A series of 2-alkoxyimino-N-(2-isoxazolin-3-ylmethyl)acetamides and related compounds were synthesized and their antiviral activities against human influenza A virus were assessed. Studies of the structure-activity relationships revealed the strongest antiviral activity when position-5 of the isoxazoline ring was substituted with a tert-butyl group. When the alkoxyimino moiety was substituted with a methyl, ethyl, isopropyl or allyl group, good antiviral activity was obtained. Among the geometrical isomers at the oxime moiety, the E-isomers were more active than the Z-isomers. Among the compounds examined, (E)-2-allyloxyimino-2-cyano-N-(5-tert-butyl-2-isoxazolin-3-ylmethyl)acetamide (1j) was the most active inhibitor with an EC(50) of 3 microg/mL in vitro.

Antiviral Agents↗
PubMed2001

Activation of NF-kappa B by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK-IKK alpha /beta-I kappa B alpha and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells.

Nontypeable Hemophilus influenzae (NTHi) is an important human pathogen in both children and adults. In children, it causes otitis media, the most common childhood infection and the leading cause of conductive hearing loss in the United States. In adults, it causes lower respiratory tract infections in the setting of chronic obstructive pulmonary disease, the fourth leading cause of death in the United States. The molecular mechanisms underlying the pathogenesis of NTHi-induced infections remain undefined, but they may involve activation of NF-kappa B, a transcriptional activator of multiple host defense genes involved in immune and inflammatory responses. Here, we show that NTHi strongly activates NF-kappa B in human epithelial cells via two distinct signaling pathways, NF-kappa B translocation-dependent and -independent pathways. The NF-kappa B translocation-dependent pathway involves activation of NF-kappa B inducing kinase (NIK)--IKK alpha/beta complex leading to I kappa B alpha phosphorylation and degradation, whereas the NF-kappa B translocation-independent pathway involves activation of MKK3/6--p38 mitogen-activated protein (MAP) kinase pathway. Bifurcation of NTHi-induced NIK-IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase pathways may occur at transforming growth factor-beta activated kinase 1 (TAK1). Furthermore, we show that toll-like receptor 2 (TLR2) is required for NTHi-induced NF-kappa B activation. In addition, several key inflammatory mediators including IL-1 beta, IL-8, and tumor necrosis factor-alpha are up-regulated by NTHi. Finally, P6, a 16-kDa lipoprotein highly conserved in the outer membrane of all NTHi and H. influenzae type b strains, appears to also activate NF-kappa B via similar signaling pathways. Taken together, our results demonstrate that NTHi activates NF-kappa B via TLR2-TAK1-dependent NIK--IKK alpha/beta-I kappa B alpha and MKK3/6--p38 MAP kinase signaling pathways. These studies may bring new insights into molecular pathogenesis of NTHi-induced infections and open up new therapeutic targets for these diseases.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed2001

FK506 (tacrolimus) increases rat alpha1-acid glycoprotein expression in liver and primary cultured hepatocytes.

FK506 (tacrolimus) (10 mg/kg, s.c., 5 days) increased rat alpha1-acid glycoprotein (AGP) in serum and AGP mRNA in liver. FK506 potentiated the dexamethasone-increased AGP expression in primary cultured hepatocytes. In the luciferase promoter assay, FK506 potentiated the dexamethasone-increased promoter activity of the AGP gene in cultured rat hepatocytes, although FK506 alone had no effect on its activity. The combined effect of FK506 and dexamethasone was diminished by glucocorticoid responsive element (GRE) deletion and mutation or by an anti-glucocorticoid. These results indicated that FK506 causes the transcriptional induction of AGP, at least in part, via a glucocorticoid-mediated mechanism.

Animals↗
PubMed2001

Interaction between beta-adrenergic signaling and protein kinase C increases cytoplasmic Ca2+ in alveolar type II cells.

The interaction between beta-adrenergic signaling and the activation of protein kinase C in alveolar type II cell plays an important role in the regulation of surfactant secretion because the combined application of beta-adrenergic agonist with protein kinase C activator to the cells stimulates the secretion synergistically. However, the mechanisms underlying the interaction are not clear. In the present study, we examined the combined effect of terbutaline with phorbol 12-myristate 13-acetate (PMA) on cytoplasmic free Ca2+ concentration ([Ca2+]i) in rat alveolar type II cells. The combined application of terbutaline with PMA to the cells rapidly increased [Ca2+]i, although neither of them affected it by itself. Similar increases of [Ca2+]i were observed in other combinations, such as terbutaline with 1-oleoyl-2-acetyl-sn-glycerol, and forskolin with PMA. Either the removal of extracellular Ca2+ or the addition of Co2+ remarkably suppressed the increase of [Ca2+]i induced by the combination of terbutaline with PMA. In addition, Co2+ inhibited the phosphatidylcholine secretion induced by the combination of terbutaline and PMA. These results suggested that the [Ca2+]i increased as a result of the interaction between formation of cyclic AMP and activation of protein kinase C in alveolar type II cells, and that the increase in [Ca2+]i was mediated by the Ca2+ influx through the plasma membrane. This mechanism to modulate [Ca2+]i may play a role in the regulation of surfactant secretion by alveolar type II cells.

Adenosine Triphosphate↗
PubMed2001

Role of Rho-associated kinase in neointima formation after vascular injury.

BACKGROUND: The Rho/Rho-associated kinase (Rho-kinase) system is implicated in various cellular functions, including migration, proliferation, and apoptosis. Because a possible role of the system is suggested in neointima formation after vascular injury, we sought to examine whether a new specific Rho-kinase inhibitor, Y27632, prevents neointima formation of the balloon-injured rat carotid artery, and if so, to investigate the effects of Y27632 on migration, proliferation, and apoptosis of smooth muscle cells (SMCs) in the injured artery. METHODS AND RESULTS: Y27632 was administered intraperitoneally from 1 day before to 14 days after vascular injury. Treatment with Y27632 inhibited phenylephrine-induced Rho-kinase activation in the carotid artery on the basis of immunoblotting against the phosphorylated myosin-binding subunit of myosin phosphatase. Y27632 markedly prevented neointima formation at days 7 and 14. In controls, BrdU(+) proliferating and TUNEL(+) apoptotic SMCs were transiently and coincidentally increased in the neointima, with a peak at day 7. Y27632 significantly increased the neointimal TUNEL(+) SMCs at days 7 and 14, but not BrdU(+) SMCs. Y27642 significantly decreased the number of intimal SMCs at day 4, while not affecting the number of BrdU(+) or TUNEL(+) SMCs. Reendothelialization after balloon injury was not significantly affected by Y27632 at days 7 and 14. CONCLUSIONS: Y27632 inhibited neointima formation by enhancing SMC apoptosis and probably by suppressing early SMC migration. Therefore, a role of Rho-kinase is suggested in neointima formation after vascular injury.

Amides↗
PubMed2001

The biological effect of phthalate esters on transabdominal migration of the testis in fetal rats in comparison with the antiandrogen flutamide.

Phthalate esters are commonly used as plasticizers for polyvinyl chloride and are known to be hormone-disrupting chemicals. We previously reported that mono-n-butyl phthalate (MBP) administered to rat fetuses induced cryptorchidism postnatally. The aim of this study was to investigate the biological effect of MBP on the transabdominal migration of the testis in prenatal rats by comparing this with the prenatal effect of the antiandrogen flutamide on testicular descent. Time-pregnant Wistar King A rats were divided into three groups: group I rats (N = 3) were administered MBP 0.3 g/day by gavage from gestational days 15 to 18; group II rats (N = 3) were injected with flutamide (30 mg/day) from gestational days 15 to 18; group III rats (N = 3) were administered solvent as controls. On the 19th gestational day, all rats underwent a cesarean section and the male fetuses were dissected to examine the position of the testis, which was significantly higher in the abdominal cavity in the MBP-treated rats than in either the flutamide-treated or control rats. No significant difference was observed in the position of the testis between the flutamide-treated and control rat fetuses. Our findings suggest that maternal MBP prevented transabdominal migration of the testis in prenatal rats, which may not have been due to either an antiandrogenic or estrogenic effect of MBP, but to a direct toxic effect of MBP on the testis.

Animals↗
PubMed2001

Carbohydrate moiety of time-interval measuring enzyme regulates time measurement through Its interaction with time-holding peptide PIN.

An ATPase called EA4 seems to measure time as a diapause-duration timer in the seasonal cycle of the silkworm, Bombyx mori. A peptide named PIN seems to regulate the time measurement of EA4. We characterize the EA4 as the first step to analyse its interaction with PIN. Matrix-assisted laser desorption/ionization-time of flight-mass spectrometry shows EA4 forms an equimolar complex with PIN. The binding affinity of EA4 for PIN is about 460 nM, as measured by surface plasmon resonance. Western blot analysis of EA4 with a variety of biotinylated lectins suggests that EA4 is a glycoprotein containing N-linked oligosaccharide. On enzymatic cleavage of the glycosyl chain, the carbohydrate is revealed to be essential for the regulation of EA4-time measurement through the interaction with PIN. PIN holds the timer by binding to EA4, and the dissociation of the complex could constitute the cue for the time measurement.

Adenosine Triphosphatases↗
PubMed2001

Effect of fudosteine, a new cysteine derivative, on mucociliary transport.

We examined the effect of fudosteine ((-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic acid) on the mucociliary transport (MCT) rate in quails. The MCT rate was estimated by ash transport velocity on the tracheal mucosa of quails. Fudosteine (500 mg kg(-1), p.o.) did not affect the normal MCT rate. However, topical application of fudosteine to the tracheal mucosa dose-dependently protected the impairment of the MCT rate caused by exposure to cigarette smoke. The results suggest that fudosteine may participate in the defence mechanism in the respiratory tract against irritant gases.

Administration, Oral↗
PubMed2001

Heterogeneity of prognosis in adult IgA nephropathy, especially with mild proteinuria or mild histological features.

OBJECTIVE: The present study was undertaken to clarify the clinical course and prognosis of adult patients with primary IgA nephropathy (IgAN), especially with mild proteinuria or mild histological alternations. PATIENTS AND METHODS: A population of 735 IgAN patients whom we were able to observe for more than two years was examined. RESULTS: A total of 115 patients (15.6%) was on dialysis during the observation period. The overall 5-year renal survival rate was 92.0%. On the other hand, 166 patients (22.6%) were in clinical remission. A group with mild proteinuria included 197 patients (26.8%). Forty-seven patients of this group showed minor glomerular abnormalities, whereas 12 patients with mild proteinuria showed severe mesangial involvement. Three patients with mild proteinuria were on dialysis during the observation period, whose proteinuria was increased during the clinical course. A group with minor glomerular abnormalities included 82 patients (11.2%). Forty-seven patients of this group showed mild proteinuria, of whom 12 patients showed moderate proteinuria. However, three patients with minor glomerular abnormalities who were not on dialysis showed loss of renal function. CONCLUSION: These results indicated the heterogeneity of the course and prognosis in IgAN. Even if a patient's initial clinical or histological findings are comparatively mild, strict follow-up management is needed.

Adolescent↗
PubMed2000

Adrenomedullin increases phosphatidylcholine secretion in rat type II pneumocytes.

Adrenomedullin, a novel hypotensive peptide, has been reported to be produced in the lung as well as in the adrenal medulla. However, the effect of adrenomedullin on lung function is still poorly understood. In this study, we detected the expression of both adrenomedullin mRNA and putative adrenomedullin receptor mRNA in primary cultures of rat type II pneumocytes. Adrenomedullin increased the secretion of phosphatidylcholine, the predominant component of pulmonary surfactant, by type II pneumocytes. The increase was partly inhibited by pretreatment with the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37). Furthermore, the increased phosphatidylcholine secretion was significantly inhibited by several protein kinase C inhibitors, such as sphingosine, 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]3-(1H-indol-3-yl) maleimide (Gö6983), 3-[1-(3-amidinothio)-propyl-1H-indoyl-3-yl]3-(1-methyl-1H-++ +indoyl-3-yl ) maleimide methane sulfonate (Ro-31-8220), and staurosporine. Our results suggest that adrenomedullin can be considered a candidate autocrine modulator of surfactant secretion in type II pneumocytes.

Adrenomedullin↗
PubMed2000

Role of the JAK/STAT pathway in rat carotid artery remodeling after vascular injury.

In cultured vascular smooth muscle cells (VSMCs), Janus kinases (JAKs) and signal transducers and activators of transcription (STATs) are expressed constitutively and play a role in angiotensin II (Ang II)-induced intracellular signaling and proliferation. However, little is known regarding the relevance of these proteins to the process of vascular remodeling. The role of JAK and STAT proteins in vascular remodeling and their functional coupling with Ang II were examined in balloon-injured rat carotid artery. Immunoreactive Jak2, Tyk2, Stat1, and Stat3 were not detected in the intact artery. Immunohistostaining showed transient expressions of these JAKs and STATs in medial and neointimal VSMCs at days 2 and 5, respectively, with a peak at day 7 in both layers. The expressions declined to insignificant levels by day 14. Ang II type 1 receptors (AT(1)s) were coexpressed in the medial and neointimal VSMCs expressing Jak2 and Stat3. The Jak2 and Stat3 inductions in the injured artery were accompanied by constitutive Jak2 and Stat3 phosphorylations, which were enhanced by ex vivo Ang II stimulation via AT(1). Additionally, a Jak2 inhibitor, AG490, blocked the Ang II-induced Stat3 phosphorylation. Furthermore, local treatment with AG490 inhibited constitutive Stat3 phosphorylation and neointimal VSMC replication and subsequently reduced neointima formation in the injured artery. In conclusion, JAK and STAT proteins were inducible in medial and neointimal VSMCs after vascular injury and were functionally coupled to AT(1). The inductions of JAKs and STATs would be involved in the mechanisms of neointima formation after vascular injury.

Animals↗
PubMed2000

Time-specific effects of mono-n-butyl phthalate on the transabdominal descent of the testis in rat fetuses.

OBJECTIVE: To determine the time-specific effects of mono-n-butyl phthalate (MBP) on the transabdominal migration of the testis in fetal rats. Materials and methods Three groups of pregnant rats were administered MBP by stomach-tube feeding when the fetus was at 7-10 days of gestation in group 1, 11-14 days in group 2, and 15-18 days in group 3; controls (group 4) were given vehicle only from 7-18 days. At 20 days of gestation the fetuses were obtained by Caesarean section, and the position of the testes, the development of the gubernaculum, cranial suspensory ligament and the epididymis were examined. RESULTS: The timed intervals of MBP administration showed that the maximum inhibition of transabdominal testicular descent was at 15-18 days of gestation. There was an elongated gubernaculum and hypertrophic cranial suspensory ligament in the MBP-treated rat fetuses. Furthermore, the epididymis showed a few small ducti deferentia, although there were no remarkable changes in either the Sertoli and Leydig cells in these testes. The mean (SEM) content of testicular testosterone was significantly less (P < 0.001) in the MBP-treated rats, at 50.9 (3.8) pg/testis, than in the controls, at 676 (33.3) pg/testis. CONCLUSIONS: These findings indicate that a brief exposure to MBP during fetal development can inhibit the transabdominal migration of the testis and reduce testosterone content in rats, although the relationship between migration and the testicular testosterone content remains unknown.

Animals↗
PubMed2000

Esthetic management of an unerupted maxillary central incisor with a closed eruption technique.

In cases of orthodontic traction of unerupted teeth, gingival recession and long clinical crowns are often seen. Satisfactory esthetic demands are not always met. A case of an unerupted maxillary central incisor is presented, in which traction was used, with emphasis on the surgical technique and the direction of the pull. The result was clinically favorable. The appearance of gingival margin was restored.

Child↗
PubMed2000

Inhibition of topoisomerases by fatty acids.

The inhibitory effects of various fatty acids on topoisomerases were examined, and their structure activity relationships and mechanism of action were studied. Saturated fatty acids (C6:0 to C22:0) did not inhibit topoisomerase I, but cis-unsaturated fatty acids (C16:1 to C22:1) with one double bond showed strong inhibition of the enzyme. The inhibitory potency depended on the carbon chain length and the position of the double bond in the fatty acid molecule. The trans-isomer, methyl ester and hydroxyl derivative of oleic acid had no or little inhibitory effect on topoisomerases I and II. Among the compounds studied petroselinic acid and vaccenic acid (C18:1) with a cis-double bond were the potent inhibitors. Petroselinic acid was a topoisomerase inhibitor of the cleavable complex-nonforming type and acted directly on the enzyme molecule in a noncompetitive manner without DNA intercalation.

Animals↗
PubMed2000

Infected hepatic cyst in a patient with multiple hepatic cysts: report of a case diagnosed by change of ultrasonographic findings.

Liver cysts are commonly observed, but infection of a liver cyst is a rare complication. Although patients have clinical symptoms, such as a high-grade fever and abdominal pain, diagnosing an infected cyst by abdominal ultrasonography, computed tomography (CT) with contrast medium and magnetic resonance imagings (MRI) is not always easy. We experienced an unusual case who had only clinical symptoms, such as high-grade fever and a right quadrant abdominal pain, but no imaging findings when admitted. Careful observation using ultrasonography once a week revealed signs of an infected cyst containing echogenic fluid 32 days after admission. We performed percutaneous transhepatic cystic drainage. When a patient has liver cysts and complains of high-grade fever and abdominal pain, liver cysts should be considered as a focus of sepsis, and we recommend repeat use of ultrasonography or CT, even if no typical findings occur the first time.

Aged↗
PubMed2000

[Effects of fudosteine, a new cysteine derivative, on airway secretion in rabbits and rats].

We examined the effects of fudosteine [(-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid], a new cysteine derivative, on airway secretion in rabbits and rats. Indirect measurement of airway secretion in rabbits, which was expressed by the amount of dye excreted into the respiratory tract, was carried out according to the Sakuno's method, with some modifications. Fudosteine (500 mg/kg, p.o.) significantly increased the amount of dye excreted into the respiratory tract. As a direct method of measurement of airway secretion, the modified Perry and Boyd's method was used to collect respiratory tract fluid (RTF) in rabbits. Fudosteine (500 mg/kg, p.o.) significantly augmented the output volume of RTF, but there was no difference from the control in protein and phosphatidylcholine (PC) contents into RTF. On the other hand, fudosteine increased chloride ion concentration in broncho-alveolar lavage of rats. Fudosteine did not stimulate PC secretion in a primary culture of rat type II pneumocytes, and it did not have a mucolytic effect against gastric mucin in vitro. From the results described above, it was concluded that fudosteine may be a new cysteine derivative which offers a serous secretion.

Animals↗