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Biomedical subjects

T Ueyama

Publications and source records attributed to T Ueyama.

At least 55 records · Page 3Linked to original sources

A possible mechanism of TPA-mediated downregulation of neurotrophin-3 gene expression in rat cultured vascular smooth muscle cells.

We have previously reported that in cultured rat vascular smooth muscle cells (VSMCs), neurotrophin-3 (NT-3) gene expression was suppressed by TPA (12-O-tetradecanoyl phorbol-13-acetate), which induces an AP-1 transcription factor. In the present study, to clarify the mechanism for TPA-mediated downregulation of NT-3 gene expression, effects of cycloheximide and dexamethasone (Dex) on the TPA-mediated downregulation were examined in VSMCs. Pretreatment with cycloheximide, an inhibitor of protein synthesis, or simultaneous treatment with Dex, an inhibitor of AP-1, suppressed the TPA-mediated downregulation of NT-3 gene expression. Furthermore, co-transfection of c-fos and c-jun expression vectors into VSMCs resulted in decrease in the NT-3 gene expression. The present findings suggest that TPA-induced AP-1 de novo synthesis causes the downregulation of NT-3 gene expression in VSMCs.

Animals↗

Transanal endoscopic microsurgery for T1 rectal cancer in patients with synchronous colorectal cancer.

We treated T1 rectal cancer in three patients with synchronous colorectal cancer by transanal endoscopic microsurgery (TEM) before performing a radical operation for the second lesion. On pathological examination, all rectal specimens resected by TEM showed cancer invasion within the submucosal layer, while the margins of the specimen were completely free of cancerous tissue. Few complications were encountered with either the TEM for the rectal lesions or the succeeding radical operation for the second lesions. When patients present with synchronous colorectal cancer, including T1 rectal cancer, local excision of the rectal lesion via TEM can help to improve the patient's quality of life without affecting the curability of the disease.

Aged↗

Structure-activity relationship of polyphenols on inhibition of chemical mediator release from rat peritoneal exudate cells.

The effect of phenolic compounds in foodstuffs on histamine and leukotriene B4 (LTB4) release from rat peritoneal exudate cells and their antioxidative activity were examined to assess their antiallergenic activities. Among them, triphenols such as pyrogallol and gallic acid inhibited histamine release from the cells, but diphenols did not. On the other hand, o- and p-diphenols such as catechol and hydroquinone with strong antioxidative activity inhibited LTB4 release as strongly as pyrogallol, but an m-derivative resorcinol with weak antioxidative activity did not. Though carboxylated compounds and their noncarboxylated counterparts were antioxidative, the former exerted a much weaker inhibitory effect on the LTB4 release than the latter. In flavonols, only myricetin with a triphenolic B ring strongly inhibited histamine release, but all flavonols strongly suppressed LTB4 release irrespective of the number of OH groups in the B ring. Among flavonoids with an o-diphenolic B ring, flavonol and flavone with a C4-carbonyl group strongly inhibited LTB4 release, whereas the activity of anthocyan without C4-carbonyl was much weaker than the above compounds. These results suggest that triphenolic structure is essential for the inhibition of histamine release. On the other hand, antioxidative activity and membrane permeability of phenolic compounds seemed to be essential for the inhibition of LTB4 release. In addition, the C4-carbonyl group seemed to be important for strongly inhibiting LTB4 release.

Animals↗

Prostacyclin analog prevents stress-induced expression of immediate early genes and gastric mucosal lesions in the rat stomach.

Water immersion-restraint induced the expression of immediate early genes (IEGs) in the epithelial cells and smooth muscle cells of gastric wall of rats, in addition to its well-known effects of mucosal erosion. Pretreatment with a prostacyclin analog (beraprost), a proton pump inhibitor (lansoprazole) or a histamine H2 receptor antagonist (famotidine) prevented formation of gastric mucosal erosion, while only the prostacyclin analog inhibited expression of IEGs. The prostacyclin analog may prevent mucosal damages as well as molecular changes by ameliorating the mucosal microcirculation, and may have potential therapeutic applications.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Non-traumatic acute paraplegia associated with cervical disc herniation: a case report.

BACKGROUND: Acute paraplegia attributable to disc herniation is known to occur most frequently at the thoracic level. We report a rare case of non-traumatic acute paraplegia caused by disc herniation at the cervical level. Preoperative magnetic resonance imaging (MRI) of the present case demonstrated a spinal cord lesion as a cause of paraplegia. Although this symptom is believed to disappear rapidly after surgical treatment, there have been a few reported cases with poor neurologic recovery and permanent deficits. CASE DESCRIPTION: A 61-year-old female with a history of minor neck pain suffered from non-traumatic acute paraplegia attributable to cervical disc herniation. She underwent emergency surgery consisting of vertebrectomy, removal of herniated discs, and anterior fusion. Postoperative neurologic improvement was slow due to the cervical spinal cord lesion at the central portion of the cord, which was detected by the preoperative and postoperative MRIs. CONCLUSION: We emphasize that the MRI study is crucial for the management of patients with acute neck pain associated with cervical canal stenosis. Surgical treatment should not be delayed to avoid permanent neurologic deficits. Anterior decompression with vertebrectomy is recommended to decompress the injured spinal cord in the narrow cervical spinal canal; however, a cord lesion detected by MRI may indicate an incomplete surgical outcome.

Acute Disease↗

Paradoxical effects of pirenzepine on parasympathetic activity in chronic heart failure and control.

We studied the effect of intravenous pirenzepine (3 mg) in normal subjects (n=15, 43+/-16 years old) and in patients with chronic heart failure (n=15, 61+/-12 years old) to assess the effect of low-dose pirenzepine on vagal activity. R-R intervals and the standard deviations, low-frequency power (LF: ln ms2, 0.04-0.15 Hz), high-frequency power (HF: ln ms2, 0.15-0.40 Hz) and the ratio of low- to high-frequency power (LF/HF ratio) were measured 10 min before and after pirenzepine using a Holter analysis system. Pirenzepine was found to cause a significant increase in the R-R interval from 903+/-112 to 956+/-129 ms in the control group (P<0.0001) and from 927+/-141 to 958+/-168 ms in patients with chronic heart failure (P<0.01). Pirenzepine also increased HF significantly from 4.29+/-0.32 to 5.16+/-0.38 ln ms2 in the control group (P<0.0001) and from 4.04+/-0.16 to 4.48+/-0.24 ln ms2 in the chronic heart failure group (P<0.05). Pirenzepine did not significantly alter the LF/HF ratio in either group. We emphasize that pirenzepine appears to have a vagoinimetic effect in patients with chronic heart failure and that it may be useful for augmenting vagal control of the heart in some patients with chronic heart failure.

Adult↗

Immediate tonsillectomy for peritonsillar abscess.

OBJECTIVE: Peritonsillar abscess (PTA) is one of the most common infectious diseases of the head and neck region requiring surgical intervention to relieve symptoms such as severe throat pain, fever, dysphagia, and trismus. However, the appropriate management of PTA is still controversial. In Europe and the US, immediate tonsillectomy under general anesthesia has been accepted as the treatment for PTA. But in Japan, immediate tonsillectomy has been regarded as contraindicated for PTA because of difficulties encountered in the operation during the acute stage, as well as possible postoperative complications. METHODS: A total of 103 cases of PTA treated at our clinic during the past 16 years were reviewed; immediate tonsillectomies had been performed in 99 of them. Surgical findings, postoperative course, and bacteriological examination were surveyed. RESULTS: The results showed that immediate tonsillectomy under general anesthesia was carried out safely without complications. Dramatic relief of the symptoms was obtained within a few days following each operation. A high incidence of anaerobes was observed by bacteriological examination, suggesting that sufficient drainage is required to treat this disease. CONCLUSION: We conclude that immediate tonsillectomy should be performed for peritonsillar abscess.

Acute Disease↗

Alterations in cardiac sarcoplasmic reticulum Ca2+ regulatory proteins in the atrial tissue of patients with chronic atrial fibrillation.

OBJECTIVES: Our purpose was to determine whether atrial fibrillation (AF) patients have alterations in sarcoplasmic reticulum (SR) Ca2+ regulatory proteins in the atrial myocardium. BACKGROUND: Clinically, AF is the most frequently encountered arrhythmia. Recent studies indicate that an inability to maintain intracellular Ca2+ homeostasis with a consequent increase in membrane-triggered activity could be the primary initiating factor in some circumstances, and that cytosolic Ca2+ abnormalities are an important mediator of sustained AF. METHODS: We measured the maximum number of [3H]ryanodine binding sites (Bmax) and the expression levels of ryanodine receptor (RyR) mRNA and calcium-adenosine triphosphatase (Ca2+-ATPase) mRNA in atrial myocardial tissue from 13 patients with AF due to mitral valvular disease (MVD) and 9 patients with normal sinus rhythm (NSR). RESULTS: In AF patients, 1) Bmax was significantly lower in each atrium (0.21+/-0.03 pmol/mg [right], 0.16+/-0.04 pmol/mg [left]) than in the right atrium (0.26+/-0.08 pmol/mg) of NSR patients; 2) Bmax was significantly lower in the left atrium than in the right atrium; 3) Bmax in the left atrium was significantly lower at higher levels of pulmonary capillary wedge pressure; 4) the expression level of RyR mRNA was significantly lower in both the left (1.24 x 10(-2)+/-1.28 x 10(-2)) and right (1.70 x 10(-2)+/-1.78 x 10(-2)) atrium than in the right atrium of NSR patients (6.11 x 10(-2)+/-2.79 x 10(-2)); and 5) the expression level of Ca2+-ATPase mRNA was significantly lower in both the left (5.67 x 10(-2)+/-4.01 x 10(-2)) and right (7.71 x 10(-2)+/-3.56 x 10(-2)) atrium than in the right atrium (12.60 x 10(-2)+/-3.92 x 10(-2)) of NSR patients. CONCLUSIONS: These results provide the first direct evidence of abnormalities in the Ca2+ regulatory proteins of the atrial myocardium in chronic AF patients. Conceivably, such abnormalities may be involved in the initiation and/or perpetuation of AF.

Aged↗

Influences of bilateral endoscopic transthoracic sympathicotomy on cardiac autonomic nervous activity.

OBJECTIVES: Endoscopic transthoracic sympathicotomy (ETS) is a minimal invasive procedure of thoracic sympathetic blockage. The purpose of this study was to evaluate cardiac autonomic nervous activity after ETS in order to confirm the reliability and safety of ETS. METHODS: A series of electrophysiological studies were performed before and 1 week after bilateral 2nd and 3rd thoracic sympathicotomy in 13 patients with primary palmar hyperhydrosis. Palmar perspiration was measured under sympathetic stress, and body surface mapping was recorded in a supine position. In the head-up tilt test of 0, 30, 60 and 90 degrees, corrected QT interval (QTc) and T wave amplitude (Twa) were assessed. The power spectral analysis of heart rate variability was processed to attain power values of the low-frequency (0.04-0.15 Hz), the high-frequency (0.15-0.40 Hz) and the low/high frequency ratio. RESULTS: In all patients, the perspiration response on the palm to sympathetic stimulation was completely inhibited after ETS. Isointegral mapping revealed that ETS altered electroactivity on the heart. In the head-up tilt study, R-R intervals significantly increased after the surgery in the head-up tilt positions (P < 0.05), although there was no significant difference in the supine position. There is no significant difference in QTc and Twa before and after the surgery, both in the supine and the head-up tilt positions. There was no significant difference in the LF or HF before and after surgery, either in the supine position or the head-up tilt positions. In the LF/HF, there was no significant difference before and after surgery in the supine position. However, the LF/HF in the head-up tilt positions was significantly decreased after surgery (P < 0.05). Sympathetic suppression of ETS was recognized more obviously under the steeper head-up tilt positions. CONCLUSIONS: The influences on the cardiac autonomic nerve system of the ETS of upper thoracic sympathetic nerve were seen to be of a lesser degree at rest. However, the response to sympathetic stimulation was suppressed after the surgery.

Adolescent↗

Endothelin-1 activates p38 mitogen-activated protein kinase via endothelin-A receptor in rat myocardial cells.

In myocardial cells (MCs), endothelin-1 (ET-1) exerts various effects such as hypertrophy, and causes cellular injury. Long-term treatment with an endothelin-A (ET(A)) receptor antagonist improves the survival of rats with heart failure, suggesting that myocardial endothelin system contributes to the progression of heart failure. p38 mitogen-activated kinase (MAPK) is a member of the MAPK family and activated by several forms of environmental stresses. We show here the effect of ET-1 on p38 MAPK activation and the role of ET-1-activated p38 MAPK on morphological changes in MCs. ET-1-stimulated p38 MAPK phosphorylation was detectable within 2 min and maximal at 5 min and was concentration dependent. The maximum effect was obtained at 10 nM. An ET(A) receptor antagonist, BQ-123, but not an endothelin-B receptor antagonist, BQ-788, inhibited these reactions. A p38 MAPK inhibitor, SB203580, failed to inhibit the morphological changes associated with ET-1-induced myocardial cell hypertrophy. These results indicate that p38 MAPK is activated by ET-1 but does not contribute to the development of ET-1-induced myocardial cell hypertrophy.

Animals↗

Identification of common lipooligosaccharide types in isolates from patients with otitis media by monoclonal antibodies against nontypeable Haemophilus influenzae 9274.

Twenty-one murine monoclonal antibodies (MAbs) were induced by nontypeable Haemophilus influenzae (NTHi) 9274. Nineteen MAbs were specific for the lipooligosaccharide (LOS) as determined by enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. When the MAbs were assayed with five LOS prototype strains by ELISA, all bound to strain 3198 LOS (type III), while six of the MAbs were also reactive with LOSs from strain 1479 (type I), 5657 (type IV), or 7502 (type V). Ten MAbs had complement-mediated bactericidal activity, and three MAbs were opsonophagocytic against the homologous strain. Five LOS MAbs with different specificities were used to analyze 155 NTHi clinical isolates from the United States and from Japan. These isolates were classified into nine groups by ELISA. Only four isolates (2.6%) were not recognized by any of the five MAbs. Most of the isolates (91.6%) were in four groups which bound three of the five MAbs. One of three MAbs, 6347C11, had strong activity against the homologous strain and was also bactericidal to 45 clinical isolates (29%) which belonged to the four common patterns (25 belonged to pattern 1). These data indicate that these MAbs can be used for LOS typing in which almost all NTHi strains can be typed according to the LOS antigenicity. Among NTHi, at least one conserved LOS epitope which is a target of bactericidal antibodies exists. We conclude that strain 9274 LOS, which is the target for bactericidal antibodies, is a candidate for LOS-based NTHi vaccines.

Animals↗

Emotional stress induces immediate-early gene expression in rat heart via activation of alpha- and beta-adrenoceptors.

We have studied the adrenergic mechanisms of immediate-early gene (IEG) induction in the discrete types of cardiac cells with the use of in situ hybridization histochemistry in an immobilization-stress model in conscious rats. Expression of c-fos, fos B, c-jun, jun B, NGFI-A, and NGFI-B mRNA was rapidly upregulated in the endothelial, myocardial, and smooth muscle cells of coronary vessels by 15-45 min after the onset of immobilization. Simultaneous blockade of both alpha- and beta-adrenoceptors completely abolished expression of IEGs in these cardiac cells. Application of an alpha-agonist or beta-agonist alone to the perfused rat heart under constant pressure elicited the upregulation of IEGs in a fashion similar to that of emotional stress. These data suggest that activation of either alpha- or beta-adrenoceptor is sufficient to evoke expression of these genes and that there may be cross talk in signal transduction downstream from alpha- and beta-adrenoceptors in cardiac cells.

Adrenergic alpha-Agonists↗

Adhesive interaction between P-selectin and sialyl Lewis(x) plays an important role in recurrent coronary arterial thrombosis in dogs.

Cell adhesion molecules may play an important role in the disease process of acute coronary syndromes. We have shown a neutralizing anti-P-selectin monoclonal antibody and a sialyl Lewis(x)-containing oligosaccharide (SLe(x)-OS), an analogue of selectin ligand on leukocytes, reduce cyclic flow variations (CFVs) in a canine model of recurrent coronary arterial thrombosis, suggesting the important interaction between P-selectin and SLex for the pathophysiology of these syndromes. However, the functional role of these adhesion molecules in the thrombotic process remains unclear. Therefore, we investigated effects of SLe(x)-OS on CFVs, platelet P-selectin expression, and morphology of the stenotic site in the same model. Anesthetized open-chest dogs (n=34) were randomly divided into 4 groups after developing CFVs. Dogs intravenously received saline or graded doses of SLe(x)-OS (5, 20, or 40 mg/kg bolus) infusion followed by a continuous infusion (5 mg. kg-1. h-1) for 60 minutes. By flow cytometric analysis, P-selectin expression on platelets after CFVs was significantly upregulated during CFVs. Immunohistochemical analysis revealed the incorporation of platelets with upregulated P-selectin within thrombi at the stenotic site. Microscopic observations revealed the presence of numerous platelets adhered to leukocytes at the stenotic site on the damaged endothelium. SLe(x)-OS significantly reduced CFVs, inhibited the P-selectin expression on platelets, and prevented the adherence of platelets and leukocytes. These findings further support the notion that the adhesive interaction between P-selectin on platelets and SLe(x) on leukocytes plays an important role in platelet-mediated thrombus formation in this model.

Animals↗

[Involvement of TTV, a new infectious factor in post-transfusion hepatitis, non A-non G].

Post-transfusion hepatitis developed in 6 of 447(1.3%) patients who received transfusion even after 1992 when HCV screening by PHA method was started. The six patients were suggested as hepatitis, non-B, non-C, non-G type. Of the six patients, 4 were found to be infected with TTV, which was identified in one of the patients. The patients became positive for TTV DNA before or almost the same time as the development of hepatitis and their amounts of TTV DNA were varied depending on the ALT level, suggesting that their hepatitis might be caused by TTV. The patients who presented hepatitis became positive for TTV DNA in the 6-10th week after transfusion, whereas more than half of the patients with a slight hepatic disorder became positive in the 2-4th week after transfusion. In addition, prolonged infection with TTV was only observed in nearly half of 23 patients.

Biomarkers↗

[Lidocaine increases the granule cell excitability in hippocampal dentate area instead of affecting GABAergic inhibition].

Lidocaine is well known to have toxic effects on the central nervous system including the induction of electroencepharographic seizures and convulsions at high doses. Although lidocaine was reported to induce electroencepharographic seizures and behavioral convulsions by decreasing the strength of GABAergic synaptic inhibition, detailed mechanisms underlying the lidocaine-induced seizures remain unclear. To determine whether lidocaine decreases GABAergic inhibition or increases the cellular excitability instead of reducing GABAergic inhibition, in the present study, we examined effects of lidocaine on monosynaptic field potentials in the hippocampal dentate gyrus of urethane-anesthetized rats. Lidocaine (10-15 mg.kg-1, i.v.) decreased significantly the threshold for action potential generation instead of producing a significant decrease in GABAergic paired-pulse inhibition. The results suggest that lidocaine first produces the hyperexcitability of hippocampal neurons, which then decreases the hippocampal GABAergic inhibition by the so-called inhibition failure leading to the induction of seizures.

Action Potentials↗

Assessment of right artrial mapping and P wave-triggered signal-average in patients with paroxysmal atrial fibrillation.

To assess right atrial mapping and P wave-triggered signal-averaged electrocardiogram (ECG) in patients with paroxysmal atrial fibrillation (PAF), this study examined right atrial electrograms using atrial mapping and parameters by P wave-triggered signal-averaged ECG in 39 patients without sick sinus syndrome. Subjects were divided into those with PAF (n = 13; 60+/-13 years old) and a control group (n = 26; 49+/-19 years old). The total number of abnormal right atrial electrograms per patient was significantly greater in the PAF group (3.2+/-1.9) than in the control group (1.1+/-0.9; P < .001). The longest duration of right atrial electrogram in the PAF group tended to be greater than that in the control group (P = .06). The filtered P wave duration was significantly longer in the PAF group than in the control group (144+/-21 vs 125+/-14 ms [P < .002]). The values of the root mean square of P wave-triggered signal-averaged ECG 15 ms from the onset (RMSi 15) and 20 ms from the offset (RMSe 20) were significantly lower in the PAF group (1.1+/-0.4 microV, 1.4+/-0.5 microV) than in the control group (1.9+/-1.1 microV [P < .02], 2.1+/-0.9 microV [P < .01]). The total number of right atrial electrograms in patients with RMSi 15 of < or =1.5 microV was significantly greater than in patients with RMSi 15 of >1.5 microV (2.2+/-1.8 vs 1.3+/-1.3 [P < .05]). Thus, the total number of abnormal right atrial electrograms per patient, the total filtered P wave duration, RMSi 15, and RMSe 20 may be good indices of PAF in patients without sick sinus syndrome. RMSi 15 may reflect the total number of the abnormal right atrial electrograms per patient.

Atrial Fibrillation↗

[Anti-tumor effects of carmofur on human 5-FU resistant cells].

As a part of studies to clarify the efficacy mechanism of carmofur (HCFU), a 5-FU analog, the degree of cross-resistance to HCFU of cell lines of cultured human colon cancer DLD-1 and a stomach cancer NUGC-3, both of which had acquired resistance to 5-FU, was studied in vitro and in vivo. In vitro, both resistant cell lines showed no or little cross-resistance to HCFU under a short-term drug exposure, and very low cross-resistance to HCFU, as compared to resistance to 5-FU, under a long-term drug exposure. In therapeutic experiments using nude mice bearing parent or subcutaneously transplanted 5-FU-resistant DLD-1 cells, HCFU exerted almost the same growth-inhibitory effects on both tumors. These results suggest that HCFU itself may have its own anti-tumor mechanism, different from that of 5-FU.

Animals↗