c-Myb interferes with inflammatory IL1α-NF-κB pathway in breast cancer cells.

The transcription factor c-Myb can be involved in the activation of many genes with protumorigenic function; however, its role in breast cancer (BC) development is still under discussion. c-Myb is considered as a tumor-promoting factor in the early phases of BC, on the other hand, its expression in BC patients relates to a good prognosis. Previously, we have shown that c-Myb controls the capacity of BC cells to form spontaneous lung metastasis.

Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: impact on clinical applications.

Background/objectives: Soluble factors and cell-derived extracellular vesicles (EVs) are crucial tissue repair mediators in cell-based therapy. In the present study, we investigate the therapeutic impact of EVs released by adipose tissue-derived stem cells (ASCs) recovered from obese subjects' visceral and subcutaneous tissues.

Methods: ASCs were recovered from 10 obese (oASCs) and 6 non-obese (nASCs) participants and characterized.

The syndromes of low-renin hypertension: "separating the wheat from the chaff".

Primary aldosteronism (PA) is characterized by hypertension and suppressed renin activity with or without hypokalemia and comprises the aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia or idiopatic hyperaldosteronism (IHA). In recent series employing the aldosterone (aldo, ng/dL):renin (ng/mL.h) ratio (ARR) for screening, prevalence of PA among hypertensives soars to 8-20%; current predominance of IHA (>80%) over APA suggests the inclusion of former low-renin essential hypertensives (LREH), in whom plasma aldo can be reduced by suppressive maneuvers.

Disorders of steroid 17 alpha-hydroxylase deficiency.

The human P450c17 alpha gene (CYP17) is a single copy gene located in chromosome 10, consisting of 8 exons and 7 introns. 17 alpha-Hydroxylase/17,20-lyase deficiency is one of two hypertensive forms of congenital adrenal hyperplasia and is inherited as an autosomal recessive trait; although rare, it probably exists with twice the frequency of the 11 beta-hydroxylase deficiency. Deficient 17 alpha-hydroxylation of pregnenolone and progesterone and subsequent deficiency of the cleavage of the C-17,20 carbon bond result in the absence of sex hormone formation in both the adrenal glands and the gonads, causing hypogonadism and male pseudohermaphroditism.

A dedicated MRI apparatus for medical and industrial applications.

So far, one of the major obstacles to the development of special purpose MRI imaging apparatus has been the lack of a magnetic technology that could cater to the need for a light, compact and efficient magnet, capable of providing the required field uniformity at a reasonable cost. Today, recent advances in magnet design permit attaining, with the use solely of ferrite, low-cost, small-scale scanners, which can open up new areas of application of MRI, in both medical and industrial fields. A novel apparatus (ARTOSCAN) is described and some examples of applications in different fields are shown.

Low sodium intake enhances sensitivity of 11-deoxycortisol and deoxycorticosterone to ACTH in ACTH-suppressed normal subjects.

Continued administration of ACTH to patients with hypopituitarism produced normal increases in steroids dependent on microsomal cytochrome P450(21) and P450(17 alpha) but reduced responses of steroids dependent on mitochondrial cytochrome P450(11 beta-18). To explore possible mechanisms and to determine whether this dissociation occurs with short-term ACTH suppression, we have examined the steroid responses to ACTH after 1 h in 12 normal subjects after equilibration on sodium intakes of 124 mmol/d [normal sodium diet (NSD)], 22 mmol/d [low sodium diet (LSD)], and 240 mmol/d [high sodium diet (HSD)] before and during continued ACTH suppression with dexamethasone (DEX). Two distinct patterns of steroid responses were observed.

Steroid characteristics of mineralocorticoid adrenocortical hypertension.

Adrenocortical causes of hypertension are established by examining the mineralocorticoid hormones produced in the zona glomerulosa and zona fasciculata. In the zona glomerulosa, aldosterone excess leads to hypertension, hypokalemia, and suppressed plasma renin activity, with increased concentrations of urinary aldosterone (either as the 18-glucuronide or free aldosterone) as an index of its production. Identifying a tumor by computed tomography scan verifies the diagnosis of a correctable lesion.

Reassessment of the predictive value of the postural stimulation test in primary aldosteronism.

Postural stimulation tests (PST) from 146 patients with primary aldosteronism were reviewed: 83 had an aldosterone-producing adenoma (APA), 48 idiopathic hyperaldosteronism (IHA), nine primary adrenal hyperplasia (PAH), and six aldosterone-producing renin-responsive adenoma (AP-RA). Plasma aldosterone and cortisol levels were measured after overnight recumbency and in response to upright posture for 2 to 4 h. The test was considered invalid in 32% of the patients because cortisol levels increased during the maneuver.

17 alpha-hydroxylation deficiency.

Cases of sexual immaturity and male pseudohermaphroditism due to disorders such as androgen resistance, 5 alpha-reductase deficiency, cholesterol desmolase deficiency, 3 beta-hydroxysteroid dehydrogenase deficiency, and testicular and ovary dysgenesis can easily be distinguished from 17 alpha-OHD. None of these disturbances result in hypertension. In the only other form of juvenile hypertension due to congenital adrenal hyperplasia, 11 beta-OHD, androgen excess leads to female pseudohermaphroditism and precocious puberty in the male patient.

Mineralocorticoids in congenital adrenal hyperplasia.

While hypertension is observed in only two of the three major subtypes of congenital adrenal hyperplasia (CAH), 11 beta- and 17 alpha-hydroxylase deficiencies, deoxycorticosterone (DOC) production is increased in all. The elevated zona fasciculata (ZF) DOC produces mineralocorticoid hypertension with suppressed renin and reduced potassium concentrations. The DOC levels in 21-hydroxylase deficiency are in part produced by renin stimulation of the Zona glomerulosa (ZG) along with aldosterone.

Continuous adrenocorticotropin administration in hypopituitarism produces asynchronous increases of deoxycorticosterone and 11-deoxycortisol relative to other reduced zona fasciculata steroids.

Short term suppression of ACTH by dexamethasone effects limited reduction in plasma deoxycorticosterone (DOC) while cortisol levels are almost completely suppressed in normal control subjects. The zona fasciculata (ZF) microsomal cytochrome P-450(21) appeared less influenced by lack of ACTH than mitochondrial cytochrome P-450(11 beta-18). Eleven patients with hypopituitarism were studied to quantitate basal ZF microsomal and mitochondrial derived steroids and their acute and extended responses to ACTH.

Correctable subsets of primary aldosteronism. Primary adrenal hyperplasia and renin responsive adenoma.

Among 154 cases of primary aldosteronism seen in the General Clinical Research Center at San Francisco General Hospital, twelve patients did not fulfill established characteristics of an aldosterone producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). Eight patients had nodular adrenocortical hyperplasia; plasma and urinary aldosterone were elevated and responses to stimulatory and suppressive maneuvers demonstrated the same autonomy seen in patients with APA. This subset is designated primary adrenal hyperplasia.

Regulation of mineralocorticoid secretion by the superfused fetal monkey adrenal gland: lack of stimulation of aldosterone by ACTH.

The rhesus monkey fetal adrenal secretion of mineralocorticoids was studied in vitro. Superfusion of fetal adrenal minces (n = 6) demonstrated that the fetal adrenal secretes aldosterone as well as desoxycorticosterone, 18 hydroxydesoxy corticosterone, and 18 hydroxycorticosterone. Addition of 250 ng/ml ACTH to the superfusion medium did not result in stimulation of aldosterone, but did increase these other mineralocorticoids.

Stimulation and suppression of the mineralocorticoid hormones in normal subjects and adrenocortical disorders.

In summary, maneuvers that affect the RAS stimulate or suppress solely aldosterone and 18-OHB and have little, if any, effect on DOC, 18-OHDOC, B, or cortisol. The magnitude of aldosterone response seems to be of equal magnitude for all stimulatory or suppressive maneuvers as used in the present protocols. Although primarily originating in the ZG, some secretion of 18-OHB from the ZF is evident by its disproportionate responses (in relation to aldosterone) to maneuvers challenging ACTH.

Identification and implications of new types of mineralocorticoid hypertension.

200 patients with mineralocorticoid hypertension were studied at the Clinical Study Center. The study of 150 patients with primary aldosteronism revealed five distinct subsets based on their responses to the upright posture, after administration of intravenous saline, deoxycorticosterone acetate, and spironolactone. Two new types were identified--aldosterone producing responsive adenoma (AP-RA) and primary adrenal hyperplasia (PAH).

The regulation of the 17-deoxy steroids in man.

One must consider the 17-DOS as a biosynthetic pathway with multiple regulatory factors. ACTH is its dominant regulator but in the absence of ACTH and in conditions where plasma renin activity is increased, this biosynthetic pathway maintains its sensitivity to exogenous ACTH. Suppression of the renin system delays the general recovery of aldosterone after the removal of an aldosterone producing adenoma but not of the 17-DOS: a pattern also showed after the removal of a DOC-producing adenoma.