Self-awareness of fast eating and its impact on diagnostic components of metabolic syndrome among middle-aged Japanese males and females.

OBJECTIVE: The aim of the present study was to examine the association between subjects with self-awareness of fast eating and diagnostic components of metabolic syndrome in Japanese middle-aged male and female. PATIENTS AND METHODS: Subjects consisted of 3208 males (average age 50.6 years) and 2055 females (average age 50.0 years). Associations between subjects with self-awareness of fast eating and multiple components of metabolic syndrome (waist circumference, body mass index [BMI], blood pressure, and related blood sample tests) were evaluated. RESULTS: Significantly more males (57.7%) acknowledged themselves as "fast eater" than females (46.5%). Self-reported fast eaters showed significantly elevated body weight, BMI, and waist circumference in both genders. However, only male self-reported fast eaters showed high levels of blood pressure, fasting blood glucose, uric acid, and low-density lipoprotein (LDL)-cholesterol. CONCLUSION: Fast eating is associated with diagnostic components of metabolic syndrome. The effect of acknowledging themselves as fast eater presents a higher impact on males than on females in the middle-aged Japanese population. The present study indicates that finding subjects with self-awareness of fast eating may lead to the prevention of developing metabolic syndrome.

Potentiation of ghrelin signaling attenuates cancer anorexia-cachexia and prolongs survival.

Cancer anorexia-cachexia syndrome is characterized by decreased food intake, weight loss, muscle tissue wasting and psychological distress, and this syndrome is a major source of increased morbidity and mortality in cancer patients. This study aimed to clarify the gut-brain peptides involved in the pathogenesis of the syndrome and determine effective treatment for cancer anorexia-cachexia. We show that both ghrelin insufficiency and resistance were observed in tumor-bearing rats. Corticotropin-releasing factor (CRF) decreased the plasma level of acyl ghrelin, and its receptor antagonist, α-helical CRF, increased food intake of these rats. The serotonin 2c receptor (5-HT2cR) antagonist SB242084 decreased hypothalamic CRF level and improved anorexia, gastrointestinal (GI) dysmotility and body weight loss. The ghrelin receptor antagonist (D-Lys3)-GHRP-6 worsened anorexia and hastened death in tumor-bearing rats. Ghrelin attenuated anorexia-cachexia in the short term, but failed to prolong survival, as did SB242084 administration. In addition, the herbal medicine rikkunshito improved anorexia, GI dysmotility, muscle wasting, and anxiety-related behavior and prolonged survival in animals and patients with cancer. The appetite-stimulating effect of rikkunshito was blocked by (D-Lys3)-GHRP-6. Active components of rikkunshito, hesperidin and atractylodin, potentiated ghrelin secretion and receptor signaling, respectively, and atractylodin prolonged survival in tumor-bearing rats. Our study demonstrates that the integrated mechanism underlying cancer anorexia-cachexia involves lowered ghrelin signaling due to excessive hypothalamic interactions of 5-HT with CRF through the 5-HT2cR. Potentiation of ghrelin receptor signaling may be an attractive treatment for anorexia, muscle wasting and prolong survival in patients with cancer anorexia-cachexia.

Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus.

Brain-derived neurotrophic factor (BDNF) has been implicated in learning, depression and energy metabolism. However, the neuronal mechanisms underlying the effects of BDNF on energy metabolism remain unclear. The present study aimed to elucidate the neuronal pathways by which BDNF controls feeding behaviour and energy balance. Using an osmotic mini-pump, BDNF or control artificial cerebrospinal fluid was infused i.c.v. at the lateral ventricle or into the paraventricular nucleus of the hypothalamus (PVN) for 12 days. Intracerebroventricular BDNF up-regulated mRNA expression of corticotrophin-releasing hormone (CRH) and urocortin in the PVN. TrkB, the receptor for BDNF, was expressed in the PVN neurones, including those containing CRH. Both i.c.v. and intra-PVN-administered BDNF decreased food intake and body weight. These effects of BDNF on food intake and body weight were counteracted by the co-administration of alpha-helical-CRH, an antagonist for the CRH and urocortin receptors CRH-R1/R2, and partly attenuated by a selective antagonist for CRH-R2 but not CRH-R1. Intracerebroventricular BDNF also decreased the subcutaneous and visceral fat mass, adipocyte size and serum triglyceride levels, which were all attenuated by alpha-helical-CRH. Furthermore, BDNF decreased the respiratory quotient and raised rectal temperature, which were counteracted by alpha-helical-CRH. These results indicate that the CRH-urocortin-CRH-R2 pathway in the PVN and connected areas mediates the long-term effects of BDNF to depress feeding and promote lipolysis.

Induced expression of c-fos in the diencephalon and pituitary gland of goats following transportation.

To identify regions of the caprine diencephalone and pituitary gland related to transportation stress, the expression of c-fos protein was examined immunohistochemically as an indicator of neural activation. Ten castrated Shiba goats (Capra hircus), five transported and five controls, were used. Transported goats were trucked for 1 h and killed by transcardiac perfusion 1 h after the end of transportation. Control goats were housed in single pens killed in the same manner and at the same time as the transported goats. The diencephalon and the pituitary gland were removed after perfusion and used for immunostaining. Plasma cortisol concentrations during and after transportation also were investigated. During transportation, plasma cortisol concentrations increased (P < 0.05) compared with those in the controls. In the diencephalon, c-fos immunoreactive cells were detected in the subcallosa, the lateral septal area, the bed nucleus of stria terminalis (BNST), the preoptic hypothalamic area (POA), the suprachiasmatic nucleus (SCN), the supraoptic nucleus, the paraventricular hypothalamic nucleus parvocellular (PVNp), the paraventricular hypothalamic nucleus magnocellular (PVNm), the arcuate nucleus (ARC), the paraventricular thalamic nucleus, and the stria medullaris in both control and transported goats. The numbers of c-fos immunoreactive cells were increased (P < 0.05) by transportation in the PVNm, the PVNp, the BNST, the POA, the ARC, and the SCN (P < 0.10). In the anterior pituitary gland, the number of c-fos immunoreactive cells in transported goats was 4 to 30 times as much as in control goats; however, there were no differences in the intermediate and posterior lobes between control and transported goats. This study has identified regions in the caprine diencephalon and pituitary gland that show transport-induced increases in c-fos immunoreactive cells. In conclusion, the PVNm, the PVNp, the BNST, the POA, the SCN in the diencephalons, and the anterior lobe of pituitary gland may be involved in the stress responses of goats to transportation.

Vasospastic total occlusion at the left main tract in a single coronary artery.

A 64-year-old man was admitted to hospital under the suspicion of unstable angina pectoris. Coronary angiography showed that he has a single coronary artery originating from the right coronary artery (RCA) without significant fixed stenosis. Acetylcholine was superselectively infused into the left main coronary artery (LMCA), and confirmed the coronary vasospastic occlusion associated with chest pain and elevation of the ST-segment in the precordial leads. This is the first report of the induction of a totally occlusive spasm of the LMCA of a patient with a RCA type single coronary artery, and this case suggests that spasm of the aberrant coronary artery is a potential mechanism for sudden death in patients with a single coronary artery.

A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia.

Genetically modified mice serve as a powerful tool to determine the role of specific molecules in a wide variety of biological phenomena including vascular remodeling. Several models of arterial injury have been proposed to analyze transgenic/knock-out mice, but many questions have been raised about their reproducibility and physiological significance. Here, we report a new mouse model of vascular injury that resembles balloon-angioplasty. A straight spring wire was inserted into the femoral artery via arterioctomy in a small muscular branch. The wire was left in place for one minute to denude and dilate the artery. After the wire was removed, the muscular branch was tied off and the blood flow of the femoral artery was restored. The lumen was enlarged with rapid onset of medial cell apoptosis. While the circumference of the external elastic lamina remained enlarged, the lumen was gradually narrowed by neointimal hyperplasia composed of smooth muscle cells. At 4 weeks, a concentric and homogeneous neointimal lesion was formed reproducibly in the region where the wire had been inserted. Similar exuberant hyperplasia could be induced in all strains examined (C57BL/6J, C3H/HeJ, BALB/c, and 129/SVj). This model may be widely used to study the molecular mechanism of post-angioplasty restenosis at the genetic level.

Nodular lung disease with five year survival and unilateral pleural effusion in AL amyloidosis.

A 67-year-old female patient with biopsy proven AL systemic amyloidosis developed rapidly progressive dyspnea. Chest roentgenogram and CT scan revealed a large right pleural effusion in addition to nodular lesions with bilateral hilar lymphadenopathy. The patient's serum showed IgG lambda type monoclonal gammopathy and she also had Bence Jones proteinuria. The pleural effusion was an exudate that contained many mononuclear cells and a high concentration of protein. Cardiac function was not seriously disturbed. Except for amyloidosis, no other causes for the severe pleural effusion were found. This patient was treated with chemical pleurodesis using Picibanil and a low dose of prednisolone. Eighteen months after this treatment, her right pleural effusion did not recur. Bronchopulmonary tissues are known to be frequently involved by AL systemic amyloidosis, but a nodular pattern of pulmonary amyloid deposition and a unilateral large pleural effusion are rare clinical manifestations in this disease.

Specific binding of Burkholderia pseudomallei cells and their cell-surface acid phosphatase to gangliotetraosylceramide (asialo GM1) and gangliotriaosylceramide (asialo GM2).

Specific binding between bacterial cells and host tissue is an early step of the pathogenesis of infection. Burkholderia pseudomallei cells, the causative micro-organisms of melioidosis, were demonstrated to bind specifically to tissue glycolipids (asialo GM1 and asialo GM2) by solid phase binding assay on thin layer chromatograms. The detection limit was around 400 pmol of the glycolipids. Acid phosphatase purified from the culture filtrate of B. pseudomallei was tested for such binding properties, and the same results were obtained. According to our previous studies, the enzyme is a glycoprotein located on the cell surface, and hydrolysed tyrosine phosphate most actively among the substrates so far tested. The mode of binding between the enzyme and the glycolipids was analyzed by comparison of binding levels among three samples different in protein content, sugar content and specific phosphatase activities per protein and sugar residue. The results suggested the possibility of a receptor-ligand relationship between the bacterial enzyme and the host-cell glycolipids (asialo GM).

Sialidase of swine influenza A viruses: variation of the recognition specificities for sialyl linkages and for the molecular species of sialic acid with the year of isolation.

The sialidase of swine influenza A viruses of N1 and N2 subtypes, isolated from 1930 to 1992, was studied for substrate specificity with ganglio-series, lacto-series type II and GM3 gangliosides containing Neu5Ac alpha 2-3Gal, Neu5Gc alpha 2-3Gal and Neu5Ac alpha 2-6Gal linkages. All viral sialidases tested showed that the activity for hydrolysing substrates with Neu5Ac alpha 2-3Gal was higher than the activities with Neu5Gc alpha 2-3Gal and Neu5Ac alpha 2-6Gal linkages. When GM1b, GM3 and sialylparagloboside were used as substrates, the earliest strain (A/Wisconsin/15/30 H1N1, isolated in 1930) showed the activity ratio of Neu5Ac alpha 2-6Gal to Neu5Ac alpha 2-3Gal to be 0.13:0.2, and the ratio Neu5Gc alpha 2-3Gal/Neu5Ac alpha 2-3Gal to be 0.19:0.37, while those strains isolated from 1978 to 1992 exhibited ratios of 0.29:0.58 for Neu5Ac alpha 2-6Gal/Neu5Ac alpha 2-3Gal and 0.51:0.76 for Neu5Gc alpha 2-3Gal/Neu5Ac alpha 2-3Gal. The above results indicate that the substrate specificities of sialidases from swine influenza A viruses towards sialyl linkages and the molecular species of sialic acid are related to the year of isolation, i.e. strains isolated after 1978 exhibited higher activity towards Neu5Ac alpha 2-6Gal and Neu5Gc alpha 2-3Gal linkages when compared with strains isolated in an earlier year, 1930.

Further studies on rat cathepsin E: subcellular localization and existence of the active subunit form.

The subcellular localization of rat neutrophil cathepsin E was examined by a modification of the method of N. Borregaard et al. [(1983) J. Cell Biol. 97, 52-61]. When the postnuclear cavitate of rat neutrophils was subjected to density centrifugation on discontinuous Percoll gradients, three particulate bands, P1 (lowest; azurophil granule rich), P2 (middle; specific granule rich), and P3 (highest; plasma membrane rich), were segregated. A combined application of immunochemical and electrophoretic methods revealed a striking difference in subcellular localization between cathepsin E and cathepsin D: Cathepsin E was associated with P3 and soluble fractions, and cathepsin D was chiefly associated with P1 and P2 fractions. The results thus indicate that cathepsin E is a nonlysosomal acid proteinase in rat neutrophils. It was found that cathepsin E existed in two enzymatically active molecular forms, referred to as CE-I and CE-II, in rat neutrophil extracts. To examine the relationships between the two forms, cathepsin E was purified to homogeneity from rat gastric mucosae. The purified enzyme exhibited a single protein band of 43 kDa on sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, but electrophoresis without SDS, followed by visualization of activity in the gel, revealed two activity bands corresponding to CE-II and CE-I in neutrophil extracts. Pretreatment of the enzyme with beta-mercaptoethanol or dithiothreitol resulted in an increase in CE-I activity with a concomitant decrease in CE-II activity on gels. Upon gel filtration, the molecular weights of CE-II and CE-I were estimated to be 98,000 and 51,000, respectively, strongly suggesting that they are the dimeric and monomeric forms of the cathepsin E subunit.