Six missense mutations of the epithelial sodium channel beta and gamma subunits in Japanese hypertensives.

Liddle's syndrome is an autosomal dominant disease characterized by sodium-sensitive early hypertension and mutations in either the beta- or gamma-subunit of the amiloride-sensitive epithelial sodium channel encoded by SCNN1B and SCNN1G. We sequenced the 381 bp-coding regions in exon 13 of SCNN1B and the 381 bp-coding regions in exon 12 of SCNN1G in 948 and 953 Japanese patients with hypertension, respectively. In the SCNN1B gene, we identified three missense mutations, P592S (n=3), T594M (n=2), and E632K (n=1) in a heterozygous state in addition to four synonymous ones, Ile515 (n=1), Ser520 (n=19), Ser533 (n=1), and Thr594 (n=11).

PIG7/LITAF gene mutation and overexpression of its gene product in extramammary Paget's disease.

To identify cancer-related genes that are involved in the carcinogenesis of extramammary Paget's disease (EMPD), we compared mRNA expression profiles of EMPD lesions and corresponding normal skin using cDNA array. Sixty-eight genes were highly expressed (>5-fold) in EMPD lesions compared to normal skin, and 40 genes were expressed less than one-fifth in EMPD lesions. Among them, PIG7/LITAF mRNA was overexpressed in 3 of 4 EMPD cases.

XPA gene-deficient, SCF-transgenic mice with epidermal melanin are resistant to UV-induced carcinogenesis.

Photobiologic investigations have been performed using animals without epidermal melanocytes. We developed xeroderma pigmentosum group A gene-deficient (XPA (-/-)), stem cell factor transgenic (SCF-Tg) mice, which one defective in nucleotide excision repair and have epidermal melanocytes, and investigated protective effects of epidermal melanin against UV-induced injuries. When irradiated to UVB, XPA (-/-) mice developed greatly enhanced responses including acute inflammation, cyclobutane pyrimidine dimer (CPD) formation, keratinocyte apoptosis, depletion of Langerhans cells and immunosuppression of contact hypersensitivity, but XPA (-/-), SCF-Tg mice showed much less responses to the same dose of UVB.

Direct effects of high glucose and insulin on protein synthesis in cultured cardiac myocytes and DNA and collagen synthesis in cardiac fibroblasts.

The present study examined the direct effects of high glucose and insulin on protein synthesis in cardiac myocytes and DNA and collagen synthesis in cardiac fibroblasts. Cultured rat cardiac myocytes and fibroblasts were grown in media containing normal glucose, high glucose, or osmotic control, and incubated with or without insulin. In cardiac myocytes, high glucose had no effect, but insulin increased protein synthesis and atrial natriuretic peptide (ANP) secretion and gene expression.

Treatment of acquired perforating dermatosis with narrowband ultraviolet B.

Acquired perforating dermatosis is difficult to treat. We describe effective therapy of acquired perforating dermatosis with narrowband UVB in 5 patients. Phototherapy was given 2 or 3 times weekly.

Three novel missense mutations of WNK4, a kinase mutated in inherited hypertension, in Japanese hypertensives: implication of clinical phenotypes.

Background: Mutations in serine-threonine kinase WNK4 with no lysine (K) at a key catalytic residue cause familial hypertension known as pseudohypoaldosteronism type II (PHAII). The objective of this study was to test whether more subtle changes of WNK4 could be implicated in hypertension or renal failure.

Methods: We screened 956 Japanese patients with hypertension or renal failure for mutations in exons 7 and 17 in the WNK4 gene where the mutations were identified in patients with PHAII.

Ultraviolet B radiation suppresses endocytosis, subsequent maturation, and migration activity of langerhans cell-like dendritic cells.

Langerhans cells capture exogenous antigens through fluid phase pinocytosis and receptor-mediated endocytosis and migrate to lymph nodes, where they present processed antigen to T cells. Ultraviolet B radiation impairs the antigen-presenting function of Langerhans cells, resulting in antigen-specific immunosuppression of contact hypersensitivity. We tested the notion that ultraviolet B radiation inhibits the endocytic activity of Langerhans cells, leading to impaired migration and maturation.

Close association of endothelial dysfunction with insulin resistance and carotid wall thickening in hypertension.

Background: Endothelial dysfunction has been regarded as an early stage in the atherosclerotic process. Endothelial dysfunction and insulin resistance were observed in hypertensive subjects and were associated with carotid wall thickening.

Methods: We examined the determinants of endothelial dysfunction including insulin sensitivity and carotid wall thickening.

Inhibitory influences of xanthine oxidase inhibitor and angiotensin I-converting enzyme inhibitor on multinucleated giant cell formation from monocytes by downregulation of adhesion molecules and purinergic receptors.

Background: Allopurinol, a xanthine oxidase inhibitor, and captopril, an inhibitor of angiotensin I-converting enzyme, are widely used for hyperuricaemia and hypertension, respectively. There have been reported cases showing that these two agents are effective for the treatment of granulomatous diseases such as sarcoidosis, although the mode of action is not elucidated.

Objectives: We examined the in vitro effects of these agents on the formation of multinucleated giant cells (MGC) from human monocytes by concanavalin A-stimulated mononuclear cell supernatants (conditioned medium).

Plasma adrenomedullin concentration is increased in patients with peripheral arterial occlusive disease associated with vascular inflammation.

Adrenomedullin (AM), a potent vasodepressor, is known to have anti-atherosclerotic and anti-inflammatory effects. However, there is no information about its level in severe atherosclerotic diseases, such as peripheral arterial occlusive disease (PAOD). The present study investigated the plasma concentration of AM and several inflammatory parameters in 72 patients with and without PAOD.

Inhibitory effect of C-type natriuretic peptide (CNP) on cultured cardiac myocyte hypertrophy: interference between CNP and endothelin-1 signaling pathways.

C-type natriuretic peptide (CNP) is known to play a role in the local regulation of vascular tone. We recently found that CNP is also produced by cardiac ventricular cells. However, its local effect on myocyte hypertrophy remains to be elucidated.

Ventricular nonmyocytes inhibit doxorubicin-induced myocyte apoptosis: involvement of endogenous endothelin-1 as a paracrine factor.

A cross-talk between cardiac myocytes and nonmyocytes via humoral factors plays an important role in the development of cardiac growth. However, it remains to be elucidated whether humoral factors produced from nonmyocytes have a protective effect on acute myocardial injury. The present in vitro study investigated the antiapoptotic effect of nonmyocytes on doxorubicin (DOX)-induced myocyte apoptosis and its molecular mechanism.

Association between left ventricular diastolic dysfunction and renal hemodynamic change in patients with treated essential hypertension.

The heart and kidneys are important target organs in hypertension. Early signs of hypertensive target organ damage can be detected by evaluating left ventricular (LV) diastolic function and intrarenal hemodynamics using Doppler ultrasonography. However, it has not been sufficiently clarified whether cardiac damage and renal impairment progress in parallel, especially from the early stage.

Carotid intima-media thickness is correlated with impairment of coronary flow reserve in hypertensive patients without coronary artery disease.

Hypertensive individuals occasionally experience angina-like chest pain despite having angiographically normal coronary arteries, and the etiology of this phenomenon has been suggested to be associated with depressed coronary flow reserve (CFR). Carotid intima-media thickness (IMT) assessed by ultrasound is correlated with not only cerebrovascular disease but also coronary artery disease and left ventricular hypertrophy (LVH). The aim of our study was to investigate the association between CFR and carotid IMT in patients with essential hypertension.

Diagnostic value of carotid intima-media thickness and plaque score for predicting target organ damage in patients with essential hypertension.

Carotid intima-media thickness (IMT) assessed by ultrasonography is regarded as an early predictor of general arteriosclerosis in patients with essential hypertension. However, the methods of measuring IMT have not been globally standardized, and it remains unclear whether conventional measurement of IMT represents the prevalence of hypertensive target organ damage. In this study, we verified the association between several commonly used carotid ultrasonographical parameters and the severity of hypertensive target organ damage (retinal arteriosclerosis, microalbuminuria, left ventricular hypertrophy (LVH)).

Gamma-tubulin in basal land plants: characterization, localization, and implication in the evolution of acentriolar microtubule organizing centers.

Although seed plants have gamma-tubulin, a ubiquitous component of centrosomes associated with microtubule nucleation in algal and animal cells, they do not have discrete microtubule organizing centers (MTOCs) comparable to animal centrosomes, and the organization of microtubule arrays in plants has remained enigmatic. Spindle development in basal land plants has revealed a surprising variety of MTOCs that may represent milestones in the evolution of the typical diffuse acentrosomal plant spindle. We have isolated and characterized the gamma-tubulin gene from a liverwort, one of the extant basal land plants.

Expression of Arabidopsis gamma-tubulin in fission yeast reveals conserved and novel functions of gamma-tubulin.

gamma-Tubulin localizes to microtubule-organizing centers in animal and fungal cells where it is important for microtubule nucleation. Plant cells do not have morphologically defined microtubule organizing centers, however, and gamma-tubulin is distributed in small, discrete structures along microtubules. The great difference in distribution has prompted speculation that plant gamma-tubulins function differently from animal and fungal gamma-tubulins.

EMG activities of facial and chewing muscles of human adults in response to taste stimuli.

To evaluate facial expression patterns induced by different taste stimuli, electromyograms (EMG) of the facial and chewing muscles of 12 healthy university students, aged 20 to 23 years, were analyzed. Sucrose (sweet), NaCl (salty), citric acid (sour), quinine-HCl (bitter), monosodium glutamate (MSG; umami), homogentisic acid (harsh), tannic acid (astringent), and capsaicine (pungent) were the taste stimuli used. Rating scale tests were made to assess the hedonics (pleasantness) of the taste stimuli.

Influence of low high-density lipoprotein cholesterol on left ventricular hypertrophy and diastolic function in essential hypertension.

Background: Left ventricular (LV) hypertrophy and LV diastolic dysfunction, which are common cardiac changes in hypertensive patients, are modified by several nonhemodynamic (eg, genetic, neurohumoral, and metabolic) factors. However, the influence of serum lipids on these LV changes has not been sufficiently studied. Although low high-density lipoprotein (HDL) cholesterol is well known to be a major risk factor for coronary heart disease, it is unclear whether HDL cholesterol plays a role in hypertensive heart disease.

Microalbuminuria and cardiovascular events in elderly hypertensive patients without previous cardiovascular complications.

To assist in the development of better treatments for elderly hypertensive patients, we studied the degree to which the baseline values of urinary albumin excretion (UAE) and other cardiovascular risk factors were predictive of cardiovascular complications in a cohort of elderly hypertensive patients. In 1994, we adopted 144 elderly hypertensive patients, who had been treated for more than 6 years at various clinics and more than 1 year at the National Cardiovascular Center, Osaka, Japan. They were divided into 2 groups: a NA group (n=111) with normoalbuminuria (UAE<30mg/day) and an MA group (n=33) with microalbuminuria (UAE 30-300 mg/day).

Induction by staurosporine of hepatocyte growth factor production in human skin fibroblasts independent of protein kinase inhibition.

Staurosporine is one of the most potent and well known inhibitors of protein kinases, and it is often used to study the involvement of protein kinases in signal transduction pathways. We now report that staurosporine can induce the production of hepatocyte growth factor (HGF) independently of protein kinase inhibition. Staurosporine markedly stimulated the production of HGF in various cell types, including human skin fibroblasts.

cDNA microarray analysis of altered gene expression in Ara-C-treated leukemia cells.

The acute lymphoblastic leukemia cell line CCRF-CEM is sensitive to Ara-C and undergoes apoptosis. In contrast, the chronic myelogenous leukemia (CML) cell line K562 is highly resistant to Ara-C, which causes the cells to differentiate into erythrocytes before undergoing apoptosis. We used cDNA microarrays to monitor the alterations in gene expression in these two cell lines under conditions leading to apoptosis or differentiation.

Efficacy of screening for primary aldosteronism by adrenocortical scintigraphy without discontinuing antihypertensive medication.

Background: Recently, it has been proposed that discontinuation of antihypertensive medications is not necessarily essential for the measurement of plasma aldosterone-to-renin ratios. We examined the efficacy of adrenocortical scintigraphy performed without modification of antihypertensive medications.

Methods: A retrospective study was conducted on 119 patients, in whom functional tests, anatomic studies, and adrenocortical scintigraphy were replete.

Circulating CD14+ CD16+ monocytes are expanded in sarcoidosis patients.

Sarcoidosis is a systemic disease of unknown etiology characterized by noncaseating granulomas, consisting mainly of epithelioid cells and multinucleated giant cells derived from monocyte-macrophage lineage cells. Monocytes fall into subpopulations comprising CD14++ CD16-, and CD14+ CD16+ cells, and expansion of the later monocytes has been reported under some pathological conditions. In this study, we examined the immunophenotype of blood monocytes in patients with sarcoidosis using two-color immunofluorescence flow cytometry.