Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma

Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti‐tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage‐independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1 attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic expression of constitutively active AKT greatly reduced apoptosis induced by Tid1 overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Prevalence and time of appearance of Brugada electrocardiographic pattern in young male adolescents from a three-year follow-up study

The prevalence of Brugada's electrocardiographic (ECG) pattern in 7,022 male adolescents in the seventh grade was determined, and the same subjects were reexamined 3 years later, while in tenth grade. Two subjects (0.03%) and 7 subjects (0.10%) showed Brugada's ECG pattern by the conventional criterion (J point or ST-segment >/=0.1 mV in leads V(1) to V(3)), and no subjects (0%) and 2 subjects (0.03%) fulfilled the recent criterion (J point or ST-segment >/=0.2 mV) in the seventh and tenth grades, respectively, indicating that Brugada's ECG pattern begins to appear during junior high school and increases until late adulthood.     

Adaptation to sustained high plasma vasopressin in water and electrolyte homeostasis in the rat transgenic for the metallothionein-vasopressin fusion gene

Prolonged exposure of tissues to a receptor agonist often leads to adaptive changes that limit the subsequent responsiveness of the tissue to the same agonist. Recently, we have generated rats transgenic for the metallothionein I-human arginine vasopressin (AVP) fusion gene (Tg), which produced high plasma AVP with relatively preserved renal water excretion, suggesting that there might be adaptive mechanism(s) for maintaining water and electrolyte homeostasis against chronic AVP oversecretion from the earliest stage of life. In this study, to investigate whether down-regulation of AVP V2 receptor (V2R), which could possibly be caused by long-standing high plasma AVP, participates in this adaptive mechanism(s), non-peptidic V2R antagonist OPC31260 was administered to reverse the down-regulation, and water loading was performed after V2R antagonist treatment had been withdrawn. Additionally, to confirm the down-regulation, Northern blotting analysis for V2R mRNA was carried out. Tg rats showed slightly decreased urine volume and water intake with an equivalent plasma [Na(+)] level (Tg 140.4 +/- 0.6 mEq/l; control 139.3 +/- 0.6 mEq/l) under basal conditions. After water loading using a liquid diet containing zinc, which stimulates the promoter region in the transgene, the urine increase showed only limited suppression with a dramatically increased plasma AVP level and mild hyponatremia (135.8 +/- 1.8 mEq/l) in Tg rats. When diet containing OPC31260 had been provided for 4 days until the day before the start of water loading, antidiuresis and hyponatremia (125.4 +/- 1.mEq/l) were significantly potentiated. V2R mRNA expression in kidney was significantly less in Tg rats than in control rats under basal conditions, and this suppression was restored by OPC31260 treatment to levels comparable with those of control rats. These results suggest that long-standing high plasma AVP causes V2R down-regulation, and it may play an important role in the adaptive mechanism(s) for maintaining water and electrolyte homeostasis in chronically AVP-overexpressing rats.     

Marked alternans of the elevated ST segment during occlusion of the left anterior descending coronary artery in percutaneous transluminal coronary angioplasty: clinical background and electrocardiographic features.

To investigate the clinical background and the electrocardiographic features of marked alternans of the elevated ST segment during coronary angioplasty, we examined 12-lead electrocardiograms recorded continuously during occlusion of the left anterior descending coronary artery by balloon inflation in 41 patients. The incidence of marked ST alternans was 27% of 41 patients and 15% of 117 balloon occlusions. The incidence decreased progressively from the first to the third occlusion. The time course of ST alternans was determined. Compared with patients without ST alternans, patients with ST alternans had a shorter history of angina, less severe stenosis of the target lesion before coronary angioplasty, more leads showing ST elevation during occlusion, higher ST elevation during occlusion and lower incidence of previous myocardial infarction in the left anterior descending coronary arterial area. ST alternans recorded on the surface electrocardiogram may thus be considered a marker of acute severe and extensive myocardial ischemia.     

Glucocorticoids increase neuropeptide Y and agouti-related peptide gene expression via adenosine monophosphate-activated protein kinase signaling in the arcuate nucleus of rats

Recent studies suggest that the AMP-activated protein kinase (AMPK) signaling in the hypothalamus is the master regulator of energy balance. We reported in previous studies that glucocorticoids play a permissive role in the regulation of orexigenic neuropeptide Y (Npy) gene expression in the arcuate nucleus. In this study, we examined whether any cross talk occurs between glucocorticoids and AMPK signaling in the hypothalamus to regulate Npy as well as agouti-related peptide (Agrp) gene expression in the arcuate nucleus. In the hypothalamic organotypic cultures, the addition to the medium of the AMPK activator, 5-aminoimidazole-4-carboxamide-1-b-d-ribofuranoside, increased phosphorylated AMPK (p-AMPK) as well as phosphorylated acetyl-coenzyme A carboxylase (p-ACC) in the explants, accompanied by significant increases in Npy and Agrp gene expression in the arcuate nucleus. The incubation with dexamethasone (DEX) also activated AMPK signaling in the explants, accompanied by significant increases in Npy and Agrp gene expression in the arcuate nucleus. The addition of the AMPK inhibitor compound C to the medium, which blocked increases of p-AMPK and p-ACC by DEX, significantly attenuated Npy and Agrp gene expression stimulated by DEX. Furthermore, p-AMPK and p-ACC levels in the arcuate nucleus were significantly decreased in adrenalectomized rats compared with sham-operated rats, and a replacement of glucocorticoids reversed the AMPK signaling in adrenalectomized rats. Thus, our data demonstrated that glucocorticoids up-regulate the Npy and Agrp gene expression in the arcuate nucleus through AMPK signaling, suggesting that the activation of the hypothalamic APMK signaling by glucocorticoids might be essential to the energy homeostasis.     

Severity of the regional wall motion and its effects on global left ventricular diastolic filling in patients with single-vessel coronary artery disease and previous myocardial infarction: assessment with radionuclide ventriculography

The severity of the regional wall motion and its effects on the global left ventricular diastolic filling were analyzed with use of radionuclide techniques in 19 patients with isolated disease of the left anterior descending coronary artery with previous myocardial infarction. Regional maximum inward movements in the noninfarcted lateral region occurred at a time close to the global end-systole, but occurred far beyond the global end-systole in the infarcted septal and apical regions, resulting in the occurrence of the regional asynchronous wall motion between the infarcted and noninfarcted regions after the global end-systole. A positive correlation between this end-systolic asynchronous wall motion and the asynchronous filling in early diastole was found (r = 0.69, p less than 0.001). A negative correlation between the asynchronous filling in early diastole and the global peak filling rate was also found (r = -0.58, p less than 0.01). Thus, the end-systolic regional asynchronous wall motion causes the subsequent regional asynchronous filling in early diastole, which may cause impairment of the global left ventricular filling in patients with single-vessel coronary artery disease with previous myocardial infarction.