Adrenocorticotropic hormone is produced in the ventricle of patients with essential hypertension

OBJECTIVE: Aldosterone is produced in the ventricle of patients with hypertension. The present study was designed to examine whether adrenocorticotropic hormone (ACTH) and cortisol are also produced from the heart in patients with essential hypertension. METHODS: The study population consisted of 57 patients with essential hypertension and 28 control subjects. Plasma levels of ACTH, aldosterone, and cortisol were measured in the aortic root, the anterior interventricular vein and the coronary sinus during cardiac catheterization. RESULTS: The plasma levels of ACTH were significantly higher at the anterior interventricular vein and coronary sinus than at the aortic root (12.7 +/- 1.0 versus 10.7 +/- 0.9 pmol/l, P < 0.001; and 12.3 +/- 1.0 versus 10.7 +/- 0.9 pmol/l, P < 0.001, respectively) in the hypertension group, whereas there were no significant differences in the levels among these sites in the control group. The plasma levels of aldosterone were significantly higher at the anterior interventricular vein and the coronary sinus than at the aortic root (261.7 +/- 16.4 versus 239.1 +/- 15.1 pmol/l, P < 0.001; and 258.8 +/- 17.0 versus 239.1 +/- 15.1 pmol/l, P < 0.01, respectively) in the hypertension group, whereas there were no significant differences in the levels among these sites in the control group. CONCLUSIONS: ACTH as well as aldosterone is produced, but cortisol is not produced, from the ventricle of patients with essential hypertension.     

Highly visible expression of an oxytocin-monomeric red fluorescent protein 1 fusion gene in the hypothalamus and posterior pituitary of transgenic rats

We have generated rats bearing an oxytocin (OXT)-monomeric red fluorescent protein 1 (mRFP1) fusion transgene. The mRFP1 fluorescence was highly visible in ventral part of the supraoptic nucleus (SON) and the posterior pituitary in a whole mount. mRFP1 fluorescence in hypothalamic sections was also observed in the SON, the paraventricular nucleus (PVN), and the internal layer of the median eminence. Salt loading for 5 d caused a marked increase in mRFP1 fluorescence in the SON, the PVN, the median eminence, and the posterior pituitary. In situ hybridization histochemistry revealed that the expression of the mRNA encoding the OXT-mRFP1 fusion gene was observed in the SON and the PVN of euhydrated rats and increased dramatically after chronic salt loading. The expression of the endogenous OXT and the arginine vasopressin (AVP) genes were significantly increased in the SON and the PVN after chronic salt loading in both nontransgenic and transgenic rats. These responses were not different between male and female rats. Compared with nontransgenic rats, euhydrated and salt-loaded male and female transgenic rats showed no significant differences in plasma osmolality, sodium concentration, OXT, and AVP levels. Finally, we succeeded in generating a double-transgenic rat that expresses both the OXT-mRFP1 fusion gene and the AVP-enhanced green fluorescent protein fusion gene. Our new transgenic rats are valuable new tools to study the physiology of the hypothalamo-neurohypophysial system.     

PKClambda regulates glucose-induced insulin secretion through modulation of gene expression in pancreatic beta cells

Altered regulation of insulin secretion by glucose is characteristic of individuals with type 2 diabetes mellitus, although the mechanisms that underlie this change remain unclear. We have now generated mice that lack the lambda isoform of PKC in pancreatic beta cells (betaPKClambda(-/-) mice) and show that these animals manifest impaired glucose tolerance and hypoinsulinemia. Furthermore, insulin secretion in response to high concentrations of glucose was impaired, whereas the basal rate of insulin release was increased, in islets isolated from betaPKClambda(-/-) mice. Neither the beta cell mass nor the islet insulin content of betaPKClambda(-/-) mice differed from that of control mice, however. The abundance of mRNAs for Glut2 and HNF3beta was reduced in islets of betaPKClambda(-/-) mice, and the expression of genes regulated by HNF3beta was also affected (that of Sur1 and Kir6.2 genes was reduced, whereas that of hexokinase 1 and hexokinase 2 genes was increased). Normalization of HNF3beta expression by infection of islets from betaPKClambda(-/-) mice with an adenoviral vector significantly reversed the defect in glucose-stimulated insulin secretion. These results indicate that PKClambda plays a prominent role in regulation of glucose-induced insulin secretion by modulating the expression of genes important for beta cell function.     

Centrally administered neuropeptide W-30 activates magnocellular neurosecretory cells in the supraoptic and paraventricular nuclei with neurosecretion in rats

We examined the effects of i.c.v. administration of neuro-peptide W-30 (NPW30) on plasma arginine vasopressin (AVP) and plasma oxytocin (OXT) using RIA. The induction of c-fos mRNA, AVP heteronuclear (hn)RNA, and c-Fos protein (Fos) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of rats were also investigated using in situ hybridization histochemistry for c-fos mRNA and AVP hnRNA, and immunohistochemistry for Fos. Both plasma AVP and OXT were significantly increased at 5 and 15 min after i.c.v. administration of NPW30 (2.8 nmol/rat). In situ hybridization histochemistry revealed that the induction of c-fos mRNA and AVP hnRNA in the SON and PVN were significantly increased 15, 30, and 60 min after i.c.v. administration of NPW30 (1.4 nmol/rat). Dual immunostaining for Fos/AVP and Fos/OXT revealed that both AVP-like immunoreactive (LI) cells and OXT-LI cells exhibited nuclear Fos-LI in the SON and PVN, 90 min after i.c.v. administration of NPW30 (2.8 nmol/rat). These results suggest that central NPW30 may be involved in the regulation of secretion of AVP and OXT in the magnocellular neurosecretory cells in the SON and PVN.     

Immunohistochemical detection of neuroendocrine differentiation in non-small-cell lung cancer and its clinical implications

Purpose  The purpose of this study was to prospectively assess the clinical implications of neuroendocrine (NE) differentiation in non-small-cell lung cancer (NSCLC) tumors. Methods  This study accrued subjects suspected to have lung cancer who underwent diagnostic bronchoscopy. Bronchoscopically-biopsied specimens were subjected to routine pathologic examination, and immunohistochemical studies were then performed if lung cancer was diagnosed. Chromogranin-A, synaptophysin, neural cell adhesion molecule, and Leu7 were used to demonstrate NE differentiation. Results  A total of 280 subjects were accrued to this study over a period of 2 years. Among them, 149 subjects were assessable for this study, and 130 were diagnosed as having NSCLC tumors (55 adenocarcinomas, 50 squamous cell carcinomas, 24 NSCLCs not otherwise specified, and 1 typical carcinoid). Large cell NE carcinoma was not observed in this study. Immunohistochemically, NE differentiation was detected in 16% of NSCLC tumors excluding typical carcinoid. By status of NE differentiation of NSCLC tumors, progression-free survivals were similar in 73 patients undergoing non-surgical treatment (positive, n = 10; negative, n = 63) and 43 patients undergoing surgical resection (positive, n = 8; negative, n = 35), respectively. Overall survival of patients with NE-positive tumors appeared to be favorable both for those undergoing non-surgical treatment and those undergoing surgical resection, though the differences in survival were not significant (P = 0.11 and 0.35, respectively). Conclusions  NE differentiation was detected in 16% of NSCLC tumors in our study. However, the prognostic implications of the presence of this feature could not be clearly determined in this study.     

Influence of topical steroids on intraocular pressure in patients with atopic dermatitis

Background

Topical corticosteroids (TCS) can induce adverse effects, such as skin atrophy. Although TCS can cause increases in intraocular pressure (IOP), the effects of daily TCS use on IOP have not been fully elucidated. We evaluated the clinical doses of TCS and the change in the IOP during the daily treatment of atopic dermatitis (AD).

Quick epinephrine administration induces favorable neurological outcomes in out-of-hospital cardiac arrest patients

Objective

This research is to study if quick administration of adrenaline on OHCA prior to hospitalization has an effect on improving CPC1-2 at one month.

Central diabetes insipidus associated with impaired renal aquaporin-1 expression in mice lacking liver X receptor β

The present study demonstrates a key role for the oxysterol receptor liver X receptor β (LXRβ) in the etiology of diabetes insipidus (DI). Given free access to water, LXRβ(-/-) but not LXRα(-/-) mice exhibited polyuria (abnormal daily excretion of highly diluted urine) and polydipsia (increased water intake), both features of diabetes insipidus. LXRβ(-/-) mice responded to 24-h dehydration with a decreased urine volume and increased urine osmolality. To determine whether the DI was of central or nephrogenic origin, we examined the responsiveness of the kidney to arginine vasopressin (AVP). An i.p. injection of AVP to LXRβ(-/-) mice revealed a partial kidney response: There was no effect on urine volume, but there was a significant increase of urine osmolality, suggesting that DI may be caused by a defect in central production of AVP. In the brain of WT mice LXRβ was expressed in the nuclei of magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus. In LXRβ(-/-) mice the expression of AVP was markedly decreased in the magnocellular neurons as well as in urine collected over a 24-h period. The persistent high urine volume after AVP administration was traced to a reduction in aquaporin-1 expression in the kidney of LXRβ(-/-) mice. The LXR agonist (GW3965) in WT mice elicited an increase in urine osmolality, suggesting that LXRβ is a key receptor in controlling water balance with targets in both the brain and kidney, and it could be a therapeutic target in disorders of water balance.     

Combination adoptive immunotherapy with chemoradiotherapy in oral carcinomas

Background The antitumor effects of adoptive immunotherapy in combination with chemoradiotherapy were investigated in patients with oral squamous cell carcinoma. Methods Inductive chemoradiotherapy with peplomycin, 5-fluorouracil and⁶⁰Co was given to 56 patients [CRI(−)group]. A local injection of adoptive lymphokine-activated killer (LAK) cells (≈2×10⁸ cells) and small doses of interleukin-2(≈3×10⁵ U) and interferon-gamma (≈2×10⁵U) was given to 40 other patients in combination with the chemoradiotherapy [CRI(+) group]. Results Clinically, CR, PR, and LR were observed in 15 (37.5%), 24 (60.0%), and 1 (2.5%) of the patients in the CRI (+) group, respectively; and in 14 (25.0%), 38 (67.9%), and 4 of the patients (7.1%) in the CRI (−) group. The histopathological effects were correlated with the tumor remission rate, with lethal degeneration (grades III and IV), and prominent degeneration (grade IIB) in the tumor cells noted in 20 (50.0%) and 16 (40.0%) of the CRI(+) patients, respectively; and in 21 (37.5%) and 29 (51.8%) of the CRI (−) patients. Immunohistochemically, a prominent decrease of proliferating cell nuclear antigenpositive cells with a reciprocal increase of Le^Y-positve cells was induced by the chemoradioimmunotherapy. DNA fragmentation was observed in the mutant type p53-negative tumors in the CRI(+) group. Conclusion Adoptive immunotherapy with LAK cells and cytokines in combination with chemoradiotherapy induces advantageous anticancer effects resulting from necrosis and apoptosis.