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Biomedical subjects

H Kai

Publications and source records attributed to H Kai.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

[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↗

Characterization of CFTR expression in a human pulmonary mucoepidermoid carcinoma cell line, NCI-H292 cells.

The NCI-H292 cell, a human pulmonary mucoepidermoid carcinoma cell line, is commonly used for studying bacterial and viral infections of airway epithelial cells. Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) is the main cause of fetal lung infection in cystic fibrosis patients. In this study, we examined CFTR expression in NCI-H292 cells to determine whether NCI-H292 cells possess sufficient, normally functioning CFTR. The results of RT-PCR and Northern blotting analysis indicated that the CFTR gene expression level was much lower in NCI-H292 cells than in T84 cells. However, Western blotting analysis showed that protein expression in NCI-H292 cells was comparable to that in T84 cells. Furthermore, whole-cell and cell-attached patch clamp electrophysiological techniques indicated that the Cl- current induced by intracellular cAMP elevation in NCI-H292 cells was comparable to that in T84 cells. These findings suggest that NCI-H292 cells with a low level of CFTR gene expression possess enough functional CFTR to show a physiological response.

Base Sequence↗

Myeloid ELF-1-like factor up-regulates lysozyme transcription in epithelial cells.

Lysozyme is an important component of innate immunity against common pathogens at mucosal surfaces. We previously cloned and characterized the bovine lysozyme 5A (lys5A) promoter with the purpose of determining cis- and trans-acting elements controlling airway epithelial cell-specific expression. We found that such expression is controlled by protein binding to an ETS consensus sequence located approximately at -46 to -40 bp from the transcription start site. The identity of the ETS-related protein responsible for gene transactivation was unknown. In this study, we screened six ETS-related proteins by transient transfection into epithelial cells and fibroblasts. Results showed that among these factors, the myeloid Elf-1-like factor (MEF) was the most potent. Gel shift analysis of epithelial cell nuclear extracts using a lys5A probe including the ETS-binding site (-50/-31) yielded a single band with retarded mobility. This band was supershifted by an antibody directed against MEF. Supporting the possibility that MEF is responsible for functional transactivation of lysozyme in epithelial cells, we found that antisense MEF mRNA decreased lys5A promoter activity and that MEF overexpression in stably transfected cells increased lysozyme mRNA and protein expression. We conclude that MEF is required for epithelial cell transactivation of lysozyme.

Animals↗

The effect of maimendongtang on airway clearance and secretion.

We investigated the effect of Maimendongtang on airway clearance and secretion in anaesthetized quails. The oral application of 1 g/kg of Maimendongtang significantly increased tracheal mucociliary transport velocity (MCTV), whereas 100 or 300 mg/kg of Maimendongtang failed to do so. Moreover, 300 mg/kg or 1 g/kg of Maimendongtang markedly attenuated human neutrophil elastase (HNE) or DNA-induced decrease in MCTV although 100 mg/kg of Maimendongtang had little effect. Furthermore, we found that Maimendongtang significantly restored HNE-induced increases in DNA, fucose and protein contents of airway surface fluid (ASF), whereas only Maimendongtang itself significantly decreased the protein content. These results indicate that Maimendongtang increases MCTV and the increase may be, at least in part, ascribed to the amelioration of ASF in the trachea.

Airway Obstruction↗

Coronary stent deployment in a young adult with Kawasaki disease and recurrent myocardial infarction.

A 19-year-old man developed a huge coronary aneurysm and stenosis in the right coronary artery as a sequela of Kawasaki disease (KD) that resulted in recurrent episodes of myocardial infarction. Coronary ischemic events were successfully prevented after balloon angioplasty followed by coronary stent implantation into the stenotic lesion. The stent deployment may have an advantage compared with balloon angioplasty and other new devices for the treatment for patients with KD showing stenotic lesions without dense calcification.

Adult↗

Coronary sinus long sheath catheter system: a new device for transfemoral coronary sinus catheterization.

Coronary sinus catheterization requires an approach into the right atrium via the superior vena cava. This study contains information regarding a coronary sinus long sheath catheter (CS sheath) system, a new device for cannulation of the coronary sinus through the femoral approach. This method was successful in 96.9% of the cases attempted. Furthermore, cannulation using the CS sheath allowed us not only to insert several catheters into the coronary sinus for clinical use and investigation, but also to access the great and small cardiac veins easily and selectively.

Cardiac Catheterization↗

Malalignment of the sarcomeric filaments in hypertrophic cardiomyopathy with cardiac myosin heavy chain gene mutation.

OBJECTIVE: To investigate changes in the alignment of the sarcomeric filaments in hypertrophic cardiomyopathy and the effects of cardiac beta myosin heavy chain (beta-MHC) mutation on the sarcomeric ultrastructure. DESIGN: A retrospective analysis. PATIENTS: Endomyocardial biopsy samples were examined by transmission electron microscopy in seven patients with hypertrophic cardiomyopathy and beta-MHC mutation, six with hypertrophic cardiomyopathy but without the mutation, and five controls (with chest pain syndromes). MAIN OUTCOME MEASURE: Alignment of the sarcomeric filaments and the distance between neighbouring thick myosin filaments. RESULTS: In controls, cross sections of the sarcomere at the A band showed a highly organised orthohexagonal array with 6 thin actin filaments surrounding one thick myosin filament, whereas in hypertrophic cardiomyopathy the alignment of the sarcomeric filaments was sparse and disrupted. In hypertrophic cardiomyopathy with a mutation, the distance between neighbouring thick myosin filaments was greater than in controls (mean (SD) 45.3 (4.7) v 38.5 (3.5) nm, p < 0.05), and the variance of the distance was greater than in controls (8.0 (0.7) v 4.8 (1.0) nm, p < 0.001) or in patients with hypertrophic cardiomyopathy without a mutation (6.7 (0.6) nm, p < 0.05). In the latter, the variance of the distance was also greater than in the controls (p < 0.01). A significant correlation was found between the grade of the myocyte hypertrophy and the variance of the distance (r = 0.654; p < 0.01). CONCLUSIONS: The alignment of the sarcomeric filaments is disrupted in hypertrophic cardiomyopathy, particularly when there is beta-MHC mutation.

Adolescent↗

Effects of eosinophil granule major basic protein on phosphatidylcholine secretion in rat type II pneumocytes.

Eosinophils are involved in inflammatory diseases such as asthma. We previously reported that activated eosinophils increased the phosphatidylcholine (PC) secretion in primary cultures of rat type II pneumocytes. Increased PC secretion was confirmed to be partly mediated by superoxide anions released from activated eosinophils. However, the influence of eosinophil granule proteins on PC secretion is unknown at present. In this study, we determined whether eosinophil major basic protein (MBP) influences PC secretion. MBP dose dependently increased the PC secretion in rat type II pneumocytes without producing any cell damage. The MBP-induced increase in PC secretion was significantly reduced by preadministration of either H-7, a protein kinase inhibitor, or 1, 2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-AM, a chelator of intracellular Ca2+, but not by H-89, a protein kinase inhibitor. Our results suggest that the MBP-induced increase in PC secretion may provide mechanical stability and protect against lung atelectasis.

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

Mucolytic and antitussive effects of erdosteine.

To investigate the influence of erdosteine, a new homocysteine-derived expectorant, on airway clearance we studied the effects of the drug on the viscosity of mucin, on the mucociliary transport rate in quails, on airway secretion in rats and on the cough reflex in guinea-pigs. The active metabolite of erdosteine, M1 (10 microM to 1 mM), significantly reduced the viscosity of porcine stomach mucin. Erdosteine by itself did not reduce viscosity. Erdosteine significantly promoted mucociliary transport in quails and increased airway secretion in rats. The effect was still apparent 24h after administration. Erdosteine significantly suppressed citric acid-induced cough reflexes in guinea-pigs but did not suppress mechanical stimuli-induced cough reflexes. Erdosteine suppressed the reduction of the recovery volume of bronchoalveolar lavage fluid and albumin leakage into the fluid in citric acid-exposed guinea-pigs. These results indicate that erdosteine removes sputum by reducing its viscosity, and by promoting mucociliary transport and sustained enhancement of airway secretion. It also suppressed the chemical stimulation-induced cough reflex and plasma leakage into the airway. These results suggest that erdosteine is an excellent expectorant with several modes of action.

Animals↗

[Novel transcription factor MEF is associated with the function of lung epithelial cells].

Lysozyme is an important component of innate immunity against common pathogens at mucosal surfaces. We previously cloned and characterized the bovine lysozyme 5A (lys5A) promoter with the purpose of determining cis- and trans-acting elements controlling airway epithelial cell-specific expression. We found that such expression is controlled by protein binding to an ETS consensus sequence located approximately at -46 to -40 bp from the transcription start site. The identity of the ETS-related protein responsible for gene transactivation was unknown. In this study, we screened six ETS-related proteins by transient transfection into epithelial cells and fibroblasts. Results showed that among these factors, the myeloid Elf-I-like factor (MEF) was the most potent. Gel shift analysis of epithelial cell nuclear extracts using a lys5A probe including the ETS-binding site (-50/-31) yielded a single band with retarded mobility. This band was super-shifted by an antibody directed against MEF. Supporting the possibility that MEF is responsible for functional transactivation of lysozyme in epithelial cells, we found that antisense MEF mRNA decreased lys5A promoter activity and that MEF overexpression in stably transfected cells increased lysozyme mRNA and protein expression. We conclude that MEF is required for epithelial cell transactivation of lysozyme.

Animals↗

Accomplishment of time-interval activation of esterase A4 by simple removal of pin fraction.

In the seasonal cycle of the silkworm Bombyx mori, an ATPase called esterase A4 (EA4) is thought to measure time interval as a diapause-duration timer. To address the mechanism by which EA4 measures the time, we present a simple EA4 screening method. By the method, EA4 activity can be assessed with a short incubation at 25 degrees C without the need to purify the enzyme further. The method largely overcomes methodological problems that remain unanswered. Besides, the results obtained by the method establish that the time measurement is based on the moment when the time-holding factor(s) PIN (peptidyl-inhibitory needle) is removed. EA4 may originally be a complex with PIN, and external time cues such as winter cold may induce the dissociation of the complex, which in turn results in the timer activation of EA4.

Adenosine Triphosphatases↗

Deep infection and fracture healing in immediate and delayed locked intramedullary nailing for open femoral fractures.

Fifty-nine patients with 61 open femoral fractures were treated with immediate locked intramedullary (IM) nailing (group 1; n=15), delayed IM nailing following nonoperative treatment (group 2; n=42), and delayed IM nailing following external fixation (group 3; n=7). Sixteen fractures were Gustilo type I, 28 were type II, 7 were type IIIA, 6 were type IIIB, and 4 were type IIIC open fractures. Four (6.6%) deep infections occurred. Significant differences existed in the deep infection rate (DIR) between types I and II and all type III fractures (2.3% for types I and II versus 17.6% for type III). The deep infection rate did not differ significantly among the nailing groups (13.3%, 2.6%, and 15.3% for groups 1, 2, and 3, respectively), nor did the deep infection rate correlate with the degree of fracture comminution, the existence of polytrauma or polyskeletal trauma, or preexistence of superficial or pin-site infections. Seven (11.7%) of these fractures resulted in nonunion, excluding one secondary amputation; the nonunion rate correlated with fracture location. There were no significant differences in the mean fracture healing times between any of the nailing groups. These results suggest that IM nailing for the treatment of type III open femoral fractures should be considered carefully, regardless of whether it is performed immediately or delayed.

Adolescent↗